PMID- 20570972 TI - An exploration of secondary sex ratios among women diagnosed with anxiety disorders. AB - BACKGROUND: Theory suggests that natural selection conserved reactivity in part because highly reactive women spontaneously abort less fit conceptuses, particularly small males. Other literature argues that high reactivity manifests clinically as anxiety disorders. If true, births to women diagnosed with anxiety disorders should exhibit a low secondary sex ratio (i.e. ratio of male to female births). We explored whether births to women diagnosed with anxiety disorders exhibit a lower sex ratio than births to women diagnosed with other psychiatric disorders, or to women without mental health diagnoses. METHODS: We performed a case-control comparison of the secondary sex ratios among groups of women categorized by mental health diagnosis using birth records linked to data from California County Mental Health system records. We compared sex ratios among 5994 deliveries to mothers diagnosed with anxiety disorders, 23 443 deliveries to mothers diagnosed with other psychiatric disorders and 1 099 198 'comparison' births. RESULTS: Although comparison births exhibited a higher sex ratio than births to women diagnosed with anxiety disorders or with other diagnoses, differences were not statistically significant. Births to African American women diagnosed with anxiety disorders, however, exhibited sex ratios significantly lower than comparison births among African Americans (OR = 0.89, P = 0.038) or births to African American women with other mental health diagnoses (OR = 0.88, P = 0.042). CONCLUSIONS: We found that infants born to African American women diagnosed with anxiety disorders exhibited a significantly lower secondary sex ratio than reference groups. We urge confirmatory tests of our findings and discuss implications of the reactivity/anxiety hypothesis for psychiatry, obstetrics and public health. PMID- 20570973 TI - Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. AB - BACKGROUND: In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. METHODS: From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI D cycles were included. RESULTS: In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. CONCLUSIONS: Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined. PMID- 20570974 TI - Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF). AB - BACKGROUND: Premature ovarian failure (POF) is a heterogeneous disease defined as amenorrhoea for >6 months before age 40, with an FSH serum level >40 mIU/ml (menopausal levels). While there is a strong genetic association with POF, familial studies have also indicated that idiopathic POF may also be genetically linked. Conventional cytogenetic analyses have identified regions of the X chromosome that are strongly associated with ovarian function, as well as several POF candidate genes. Cryptic chromosome abnormalities that have been missed might be detected by array comparative genomic hybridization. METHODS: In this study, samples from 42 idiopathic POF patients were subjected to a complete end-to-end X/Y chromosome tiling path array to achieve a detailed copy number variation (CNV) analysis of X chromosome involvement in POF. The arrays also contained a 1 Mb autosomal tiling path as a reference control. Quantitative PCR for selected genes contained within the CNVs was used to confirm the majority of the changes detected. The expression pattern of some of these genes in human tissue RNA was examined by reverse transcription (RT)-PCR. RESULTS: A number of CNVs were identified on both Xp and Xq, with several being shared among the POF cases. Some CNVs fall within known polymorphic CNV regions, and others span previously identified POF candidate regions and genes. CONCLUSIONS: The new data reported in this study reveal further discrete X chromosome intervals not previously associated with the disease and therefore implicate new clusters of candidate genes. Further studies will be required to elucidate their involvement in POF. PMID- 20570975 TI - Clinical and biochemical correlates of successful semen collection for cryopreservation from 12-18-year-old patients: a single-center study of 86 adolescents. AB - BACKGROUND: Cryopreservation of semen should be offered to adults before gonadotoxic treatment. However, the experience with semen collection in adolescents is still limited. The objective of this study was to evaluate potential correlates of successful semen sampling in adolescents. METHODS: A total of 86 boys (aged 12.2-17.9 years), referred for cryopreservation of semen prior to gonadotoxic treatment were included. Age, testicular volume, diagnosis and reproductive hormones were evaluated as correlates of successful semen collection. RESULTS: Median sperm concentration was 9.6 (range 0-284) million/ml. Of the 86 included boys, 76 (88.4%) had spermatozoa in their ejaculate. Of the 76 patients for whom a semen sample was obtained, 71 (93.4%) had motile spermatozoa eligible for cryopreservation. Of the 86 boys, 74 produced a semen sample by masturbation, whereas semen samples were obtained from 12 patients by penile vibration or electroejaculation. The youngest patient with an ejaculate containing motile spermatozoa was 12.2 years old, and the smallest testicular volumes in boys associated with motile spermatozoa in the ejaculate were 6-7 ml. Testicular volume correlated with sperm concentration (R = 0.283, P = 0.046), and the percentage of motile spermatozoa (R = 0.410, P = 0.003). Chronological age, but not reproductive hormones, also correlated with sperm concentration (R = 0.25, P = 0.049). CONCLUSIONS: Semen was successfully collected and cryopreserved in 71 out of 86 boys and adolescents. Testicular volume, but not age or reproductive hormone levels, was indicative of successful semen collection. Regardless of their age, adolescent boys with testicular volumes of more than 5 ml should be offered semen banking prior to gonadotoxic treatment or other procedures that could potentially damage future fertility. PMID- 20570976 TI - Do statins slow the process of calcification of aortic tissue valves? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether statins slow the process of calcification of aortic tissue valves. Altogether 207 papers were found using the reported search, of which eight represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We acknowledge the limited evidence in this very specific field of cardiac surgery. Due to their pleiotropic effects, including anti-inflammatory properties, there has been speculation that statins could reduce and delay the degeneration and calcification of aortic bioprosthetic valves. Mainly, it was extrapolation of the recently discovered molecular similarities between atherosclerosis and native aortic valve stenosis (AS), with some evidence that statins may slow the progression of native aortic valve calcific degeneration, and the potential harmful impact of atherosclerotic risk factors on the development of native AS. Several studies have been conducted to evaluate the impact of hyperlipidemia and serum cholesterol levels on structural valve deterioration (SVD). Indeed, two studies suggested hyperlipidemia was a risk factor for SVD and correlated reoperation, from which one case-control study based on first-generation biological valves without specific anti-calcification treatment, while three - more convincing by number of patients observed and design of the study - reported contrary results. The other three studies focused on statin treatment in patients after aortic biological valve replacement. Two studies confirmed beneficial effects of statin therapy on valve hemodynamics or inflammatory damage in vivo, but another study, with significantly greater patients series, found lipid-lowering therapy futile in this clinical aspect. Currently, studies and their results are discordant, but statin therapy appears insufficient to result in better clinical outcomes. We conclude that even though the data is conflicting, statin therapy does not prevent SVD of bioprosthetic valves in the aortic position. PMID- 20570977 TI - Does the prophylactic administration of N-acetylcysteine prevent acute kidney injury following cardiac surgery? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'does prophylactic administration of N acetylcysteine (NAC) prevent acute kidney injury (AKI) following cardiac surgery?' More than 60 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The administration of NAC prior intravenous radioactive contrast has been shown to reduce the incidence of contrast-induced nephropathy. There have been two recent meta analyses and several randomised controlled trials (RCTs) and investigating the effectiveness of prophylactic administration of NAC in the prevention of AKI following cardiac surgery. The RCTs have investigated the use of NAC to prevent AKI in low-risk patients, high-risk patients and high-risk patients with pre existing chronic kidney disease. The meta-analyses and RCTs demonstrated that the prophylactic administration of NAC did not reduced the incidence of AKI, postoperative complications, postoperative interventions, mortality or length of ICU stay. We conclude that prophylactic administration of NAC does not prevent AKI or reduce mortality following cardiac surgery. PMID- 20570978 TI - Transapical aortic valve prosthetic endocarditis. AB - An 83-year-old patient underwent a transapical aortic valve implantation at our institution. Four months later, she was readmitted to our institution because of fever and heart failure. A prosthetic aortic valve endocarditis was diagnosed. Because of the high surgical risk, surgery was refused and the patient died shortly after the diagnosis. We briefly discuss the implications of this finding in the prevention of infective endocarditis after transcatheter aortic valve implantation. PMID- 20570979 TI - Twenty-one-year survival in an invasive thymoma successfully treated with seven fold iterative surgery. AB - A complete surgical resection is the cornerstone in the therapy of thymic tumors. Unfortunately, the recurrence of invasive thymoma is a frequent event and, to date, no standard therapeutic strategy has been validated. We report a case of a 48-year-old patient with an initial diagnosis of myasthenia gravis who underwent radical thymectomy and adjuvant radiotherapy in 1988 for an invasive thymoma. Six years after the first operation the patient was submitted to re-iterative surgery (pleural recurrence) and, as of the period from 1994 until today, the patient has been re-operated an additional five times. The last of these episodes, which we describe in this report, concerned a recurrence at the level of the sternum and the liver. To date the patient is alive and well, with no evidence of further relapse. We take the opportunity of this report to briefly discuss the re iterative surgical strategy in repetitive recurrent invasive thymoma that we advocate as feasible and beneficial if survival is benchmarked, according to the experiences reported so far. PMID- 20570980 TI - Protocol for a mixed-methods study on leader-based interventions in construction contractors' safety commitments. AB - BACKGROUND: Owing to high injury rates, safety interventions are needed in the construction industry. Evidence-based interventions tailored to this industry are, however, scarce. Leader-based safety interventions have proven more effective than worker-based interventions in other industries. OBJECTIVE: To test a leader-based safety intervention for construction sites. The intervention consists of encouraging safety coordinators to provide feedback on work safety to the client and line management. The intention is to increase communication and interactions regarding safety within the line management and between the client and the senior management. It is hypothesised that this, in turn, will lead to increased communication and interaction about safety between management and coworkers as well as an increased on-site safety level. SETTING: A group randomised double-blinded case study of six Danish construction sites (three intervention sites and three control sites). The recruitment of the construction sites is performed continuously from January 2010 to June 2010. The investigation of each site lasts 20 continuous weeks. METHODS: Confirmatory statistical analysis is used to test if the safety level increased, and if the probability of safety communications between management and coworkers increases as a consequence of the intervention. The data collection will be blinded. Qualitative methods are used to evaluate if communication and interactions about safety at all managerial levels, including the client, increase. OUTCOME MEASURES: (1) The proportion of safety-related communications out of all studied communications between management and coworkers. (2) The safety level index of the construction sites. PMID- 20570981 TI - Measuring quality of life after injury. PMID- 20570982 TI - The measurement of long-term health-related quality of life after injury: comparison of EQ-5D and the health utilities index. AB - OBJECTIVE: Empirical head-to-head comparison of the health utility index (HUI) mark 2 and 3 and the EuroQol-5D (EQ-5D) in injury patients of all severity levels to obtain more insight into the strengths and limitations of the multi-attribute utility measures (MAUI) to estimate utility losses in injury populations. DESIGN: A self-assessment survey that included the EQ-5D, HUI2 and HUI3 to measure generic health-related quality of life. PATIENTS: Injury patients in The Netherlands 2 years after they attended the emergency department. MAIN OUTCOME MEASURES: Shannon's index and Shannon's evenness index were used to assess absolute and relative informativity, both for the summary scores and by dimension. The study also analysed convergent and construct validity of the MAUI. RESULTS: Mean summary scores significantly differed between the instruments, with highest summary scores for HUI2 (0.88), followed by HUI3 (0.80) and EQ-5D (0.78). Absolute and relative informativity by dimension was highest for the HUI3 descriptive system. The HUI3 was most sensitive for ageing and comorbidity. The largest differences between the MAUI were found for pain/discomfort and anxiety/depression/emotion. The largest differences in discriminative power between EQ-5D and HUI (mark 2 and 3) were seen for skull-brain injury, internal organ injury and upper extremity fractures. CONCLUSIONS: Different MAUI resulted in significantly different summary scores. The instruments and their dimensions performed differently for injury severity levels, ageing, comorbidity and injury groups. A combination of the HUI and EQ-5D should be used in studies on injury related disability, because the combination covers all relevant health dimensions, is applicable in all kinds of injury populations and in widely different age ranges. PMID- 20570983 TI - Developing injury indicators for Canadian children and youth: a modified-Delphi approach. AB - OBJECTIVE: To develop a set of national injury indicators for Canadian children and youth which will eventually be used to reflect and monitor identified prevention priorities. METHODS: The Canadian Injury Indicators Development Team brought together injury researchers, policy makers, and practitioners to develop injury indicators in the following areas: overall health services implications; motor vehicle occupant; sports, recreation, and leisure; violence; and trauma care, quality, and outcomes. A modified-Delphi process was used to establish a set of indicators that met evidence-based criteria, were useful, and that would prompt action. Each indicator was rated by 132 respondent injury experts and stakeholders on its usefulness and ability to prompt action to reduce injury among Canadian children and youth. RESULTS: From an initial list of 51 indicators, a refined set of 34 indicators was established. Indicators were grouped into three categories related to: policies; risk and protective factors; and outcomes. Indicators related to motor vehicle injury were rated as most useful and most able to prompt action. Injury mortality rate and injury hospitalisation rate were also rated highly for both usefulness and ability to prompt action. Policy, violence, sport and recreation, and trauma indicators were all rated higher for usefulness, but somewhat lower for ability to prompt action. CONCLUSION: Results suggest that a broad-based modified-Delphi process is an important first step in developing useful and relevant indicators for injury prevention activity focused on Canadian children and youth. PMID- 20570984 TI - Injury-related childhood mortality in migrant households in a southern city of China. AB - BACKGROUND: Sporadic evidence from China suggests that migrant children are at higher risk of injury-related mortality than local indigenous children. METHODS: Child deaths from 2004 to 2008 were provided by the Shenzhen Women and Child Health Surveillance System. Population data for children 1-4 years old were obtained from the Shenzhen Bureau of Statistics and number of live births was obtained from birth registration records. All-cause and injury-related childhood mortality rates and death causes were calculated and compared. RESULTS: A total of 3774 deaths were identified. All-cause mortality rates per 10,000 dropped significantly from 66.28 (95% CI 60.50 to 72.06) in infants (<1 year old) and 7.40 (95% CI 6.16 to 8.64) in early childhood (1-4 years old) in 2004 to 40.42 (95% CI 37.31 to 43.53) and 3.97 (95% CI 3.36 to 4.58) in 2008. However, injury related mortality rates did not change significantly from 2.36 (95% CI 1.27 to 3.45) in infants and 2.97 (95% CI 2.19 to 3.76) in early childhood in 2004 to 2.00 (95% CI 1.31 to 2.69) and 2.00 (95% CI 1.56 to 2.43) in 2008. Injury-related mortality rates were significantly higher among migrant children (p<0.05). Drowning and traffic crashes were the top two causes of early childhood injury deaths; suffocation was the leading cause of infant injury deaths. CONCLUSION: Migrant children were at significantly higher risk of injury-related mortality than local indigenous children. Injury prevention in Shenzhen should target drowning and traffic safety among young children and suffocation among infants as top priorities. PMID- 20570985 TI - Sleep habits and excessive daytime sleepiness correlate with injury risks in the general population in Taiwan. AB - OBJECTIVE: To explore the relationship between sleeping habits, excessive daytime sleepiness (EDS), and different injury risks in the general population of Taiwan. DESIGN: Cross-sectional national data from the Taiwan Social Trend Survey conducted in 2005 by interviews using validated inventories. SETTING: Population based face-to-face interviews at participants' residences. PARTICIPANTS: 36,473 Taiwanese citizens aged 15 years or older. EXPOSURE MEASURES: Self-reported EDS was measured using the Epworth sleepiness scale. Other sleep-related problems investigated included self-reported sleep quality (assessed by the insomnia self assessment inventory) and self-reported inadequate sleep duration (<7 h). MAIN OUTCOME MEASURES: Self-reported major injuries that required medical attention. RESULTS: Considering all sleep-related problems together, multivariate logistic regression analyses showed that EDS and poor sleep quality were significant predictors of higher risks of various injuries. EDS predicted major traffic injuries (odds ratio (OR) 1.62, 95% CI 1.29 to 2.02) and major fall injuries (OR 1.49, 95% CI1.20 to 1.84). Those with poor sleep quality tended to have traffic injuries (OR 1.67, 95% CI 1.41 to 1.99) and major fall injuries (OR 1.73, 95% CI 1.44 to 2.07). CONCLUSIONS: EDS and sleep quality are associated with the occurrence of a variety of injuries in Taiwan's general population. PMID- 20570986 TI - Effectiveness of pads and enclosures as safety interventions on consumer trampolines. AB - BACKGROUND: Trampolines continue to be a major source of childhood injury. OBJECTIVE: To examine available data on trampoline injuries in order to determine the effectiveness of padding and enclosures. DESIGN: Trampoline injuries from the NEISS database from 2002 to 2007 were reclassified into five cause-categories, to examine evidence for injury trends. SETTING: The ASTM trampoline standard recommendations for safety padding were upgraded in 1999 and enclosures were introduced in 1997. This is the first study to examine the impact of these changes. PATIENTS: The sampling frame comprises patients with NEISS product code 'consumer trampolines' (1233). A systematic sample of 360 patients each year is taken. INTERVENTIONS: The prominent interventions recommended by the ASTM are netting enclosures to prevent falling off and safety padding to cover frames and springs. MAIN OUTCOME MEASURES: Proportion of injuries within each cause-category and trend estimates. RESULTS: There was no evidence for a decline within the injury cause-categories that should be prevented by these interventions from 2002 to 2007. CONCLUSIONS: If these interventions were effective the associated injury causes would be in decline. Instead they remain close to half of all trampoline injuries with no significant change over the period of the study. Follow-up studies are proposed to determine the reasons. Given the number of injuries involved it is recommended that steps be taken to ensure these safety interventions or their equivalents are in place, work properly and remain effective for the life of consumer trampolines. PMID- 20570988 TI - Action indicators for injury prevention. AB - There is considerable confusion about the nature of indicators, their use in the injury field and surprisingly little discussion about these important tools. To date discussions of injury indicators have focused on the content and presentation of health outcome measures and on the dearth of data on exposure measures. Whereas these are valuable measures and assessing the optimal use of available routinely collected data in forming indicators is important, they do not provide sufficient information to support comprehensive prevention efforts, nor do they harness the full potential of indicators as tools to support prevention efforts. This paper provides an overview of the characteristics and uses of indicators for the field of injury prevention in order to make the case for action indicators and provide a framework for their appropriate use. PMID- 20570987 TI - Reporting on road traffic injury: content analysis of injuries and prevention opportunities in Ghanaian newspapers. AB - In order to analyse traffic injury reporting in Ghanaian newspapers and identify opportunities for improving road safety, the content of 240 articles on road traffic injury was reviewed from 2005 to 2006 editions of two state-owned and two privately owned newspapers. The articles comprised reports on vehicle crashes (37%), commentaries (33%), informational pieces (12%), reports on pedestrian injury (10%), and editorials (8%). There was little coverage of pedestrian injuries, which account for half of the traffic fatalities in Ghana, but only 22% of newspaper reports. Only two articles reported on seatbelt use. Reporting patterns were similar between public and private papers, but private papers more commonly recommended government action (50%) than did public papers (32%, p=0.006). It is concluded that Ghanaian papers provide detailed coverage of traffic injury. Areas for improvement include pedestrian injury and attention to preventable risk factors such as road risk factors, seatbelt use, speed control, and alcohol use. PMID- 20570989 TI - The Cochrane Injuries Group celebrates the publication of its 100th review: time to reflect on impact. PMID- 20570990 TI - It wouldn't hurt to walk: promoting pedestrian injury research. PMID- 20570991 TI - UN General Assembly calls for decade of action for road safety. PMID- 20570992 TI - Prioritisation of road traffic injury prevention fund spending in developing countries. PMID- 20570993 TI - Jolted into action: untoward crises as catalysts for sustained improvement of public health. PMID- 20570995 TI - Preterm birth and psychiatric medication prescription in young adulthood: a Swedish national cohort study. AB - BACKGROUND: Recent studies suggest an increased risk of adverse mental health outcomes among young adults who were born preterm. These studies have been based mainly on hospital data, thus missing large numbers of mental health problems that do not require inpatient treatment. We used national outpatient and inpatient pharmacy data to evaluate whether individuals who were born preterm were more likely to be prescribed psychiatric medications during young adulthood than individuals who were born full term. METHODS: A national cohort of all infants born in Sweden from 1973 through 1979 [N = 635,933, including 28,799 who were born preterm (<37 weeks)] was followed to ages 25.5-34.0 years to determine whether psychotropic medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives and/or psychostimulants) were prescribed in 2005-06. RESULTS: A trend of increasing rate of prescriptions for antipsychotics, antidepressants and hypnotics/sedatives in young adulthood was observed by earlier gestational age at birth. Young adults who were extremely preterm at birth (23-27 weeks) were 3.1 times more likely to be prescribed antipsychotics [95% confidence interval (CI) 1.66-5.93], 1.8 times more likely to be prescribed antidepressants (95% CI 1.26-2.64) and 1.8 times more likely to be prescribed hypnotics/sedatives (95% CI 1.15-2.96) than individuals who were full term at birth, after adjusting for potential confounders. CONCLUSIONS: This national cohort study, using outpatient and inpatient pharmacy data, suggests that preterm birth has important independent effects on mental health that extend at least into young adulthood. PMID- 20570996 TI - {mu}-Crystallin, new candidate protein in endotoxin-induced uveitis. AB - PURPOSE. micro-Crystallin (CRYM) is a major taxon-specific lens protein. The purpose of this study was to investigate the function of CRYM in eyes of mice with endotoxin-induced uveitis (EIU). METHODS. EIU was induced by an injection of a lipopolysaccharide (LPS) into the footpad of male C57BL/6J, CRYM knockout (CRYM(-/-)), and wild-type (CRYM(+/+)) mice. The expression of CRYM in the iris ciliary body (ICB) was investigated by Western blot analyses and real-time RT-PCR at 12 hours and 1, 3, and 5 days after the LPS injection. The number of cells that had infiltrated the anterior chamber (AC) of the CRYM(+/+) mice was compared to that in the CRYM(-/-) mice at 1, 3, 5, and 7 days. The expressions of the mRNA of interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage-colony stimulating factor (GM-CSF) in the ICB of the two groups of mice were compared. RESULTS. The mRNA of CRYM was upregulated at 12 hours after LPS injection, and CRYM protein increased at 3 days. The number of inflammatory cells in the AC of the CRYM(-/-) mice was not significantly different on day 1 from that in the CRYM(+/+) mice, but was significantly lower (17.9 +/- 1.6 vs. 27.1 +/- 2.4 cells/section) on day 5. Expression of the mRNA of IL-1alpha and -6 in the CRYM(-/-) mice was significantly lower than that in the CRYM(+/+) mice on day 5. CONCLUSIONS. CRYM plays an important role in the development of the second peak of murine EIU. PMID- 20570997 TI - Treating retinoblastoma in tissue culture and in a rat model with a novel isoquinoline derivative. AB - PURPOSE. To investigate the effectiveness of a novel isoquinoline derivative, EDL 155, in killing retinoblastoma in vitro and in vivo. METHODS. Dose-response curves were generated in which Y79 retinoblastoma cells tagged with luciferase (Y79-Luc) were treated with serial concentrations of EDL-155. Electron microscopy was used to evaluate the ultrastructural morphology of EDL-155-treated Y79 cells. To determine whether autophagy was induced in EDL-155-treated Y79-Luc cells, staining with acridine orange and LC-3 immunoblot analysis was performed. To evaluate the efficacy of EDL-155 in vivo, Y79-Luc retinoblastoma cells were injected into the vitreous cavity of newborn rats, followed by periocular injections of EDL-155 (20 mg/kg/day) or an equivalent dosage of saline. RESULTS. EDL-155 appeared to destroy the retinoblastoma cells in vitro with an EC(50) of 9.1 micriM. EDL-155-treated retinoblastoma cells displayed a lack of viable mitochondria and the presence of autophagosomes wrapped in the characteristic double membranes. Acridine orange staining of EDL-155-treated retinoblastoma cells demonstrated the accumulation of vacuoles, and the immunoblots displayed a shift in molecular weight of LC-3, indicative of incorporation into autophagosome vesicles. In the retinoblastoma animal model, four doses of EDL-155 were delivered over 4 days, which was sufficient to see a significant decrease (P = 0.01) in viable intraocular tumors. Seven of the 25 rats treated with EDL-155 had no detectable living tumor. No significant decrease in viable tumor was observed in control animals. CONCLUSIONS. EDL-155 appears to eliminate retinoblastoma cells by disrupting mitochondria and inducing autophagy. Local delivery of EDL 155 may be an effective therapy for some types of ocular cancers. PMID- 20570998 TI - Clonal group distribution of fluoroquinolone-resistant Escherichia coli among humans and companion animals in Australia. AB - OBJECTIVES: To determine the phylogenetic group distribution and prevalence of three major globally disseminated clonal groups [clonal group A (CGA) and O15:K52:H1, associated with phylogenetic group D, and sequence type ST131, associated with phylogenetic group B2] among fluoroquinolone-resistant extra intestinal Escherichia coli isolates from humans and companion animals in Australia. METHODS: Clinical extra-intestinal fluoroquinolone-resistant E. coli isolates were obtained from humans (n = 582) and companion animals (n = 125), on Australia's east coast (October 2007-October 2009). Isolates were tested for susceptibility to seven antimicrobial agents, and for phylogenetic group, O type and clonal-group-specific single nucleotide polymorphisms by PCR. RESULTS: The fluoroquinolone-resistant isolates were typically resistant to multiple agents (median of four). Analysis revealed that clonal group ST131 accounted for a large subset of the human isolates (202/585, 35%), but for a much smaller proportion of the companion animal isolates (9/125, 7.2%; P or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95% CI, 1.9-4.3) and 2.0 (95% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less. CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes. PMID- 20571019 TI - Health care reform--a historic moment in US social policy. PMID- 20571020 TI - Genomic analysis of mental illness: a changing landscape. PMID- 20571021 TI - Down syndrome--new prospects for an ancient disorder. PMID- 20571022 TI - Surgical care improvement: should performance measures have performance measures. PMID- 20571015 TI - Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. AB - CONTEXT: Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. OBJECTIVE: To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. DESIGN, SETTING, AND PATIENTS: Double blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. INTERVENTIONS: 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. MAIN OUTCOME MEASURES: First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. RESULTS: Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). CONCLUSION: Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN74348595. PMID- 20571023 TI - JAMA patient page. Postoperative infections. PMID- 20571024 TI - Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts. AB - Chemokines are characterized by the homing activity of leukocytes to targeted inflammation sites. Recent research indicates that chemokines play more divergent roles in various phases of pathogenesis as well as immune reactions. The chemokine receptor, CCR1, and its ligands are thought to be involved in inflammatory bone destruction, but their physiological roles in the bone metabolism in vivo have not yet been elucidated. In the present study, we investigated the roles of CCR1 in bone metabolism using CCR1-deficient mice. Ccr1(-/-) mice have fewer and thinner trabecular bones and low mineral bone density in cancellous bones. The lack of CCR1 affects the differentiation and function of osteoblasts. Runx2, Atf4, Osteopontin, and Osteonectin were significantly up-regulated in Ccr1(-/-) mice despite sustained expression of Osterix and reduced expression of Osteocalcin, suggesting a lower potential for differentiation into mature osteoblasts. In addition, mineralized nodule formation was markedly disrupted in cultured osteoblastic cells isolated from Ccr1(-/-) mice. Osteoclastogenesis induced from cultured Ccr1(-/-) bone marrow cells yielded fewer and smaller osteoclasts due to the abrogated cell-fusion. Ccr1(-/-) osteoclasts exerted no osteolytic activity concomitant with reduced expressions of Rank and its downstream targets, implying that the defective osteoclastogenesis is involved in the bone phenotype in Ccr1(-/-) mice. The co culture of wild-type osteoclast precursors with Ccr1(-/-) osteoblasts failed to facilitate osteoclastogenesis. This finding is most likely due to a reduction in Rankl expression. These observations suggest that the axis of CCR1 and its ligands are likely to be involved in cross-talk between osteoclasts and osteoblasts by modulating the RANK-RANKL-mediated interaction. PMID- 20571025 TI - Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor. AB - Growth factors modify the structure of the glycosaminoglycan (GAG) chains on biglycan leading to enhanced LDL binding. G-protein receptor-coupled agonists such as thrombin, signal changes the structure of proteoglycans produced by vascular smooth muscle cells (VSMCs). One component of classical G-protein coupled receptor (GPCR) signaling invokes transactivation of protein tyrosine kinase receptors such as the epidermal growth factor receptor. Serine/threonine receptor growth factors such as transforming growth factor-(TGF)-beta are potent activators of proteoglycan synthesis. We have used the model of proteoglycan synthesis to demonstrate that the signaling paradigm of GPCR signaling can be extended to include the transactivation of serine/threonine receptor, specifically the TGF-beta type I receptor (TbetaRI) also known as activin-like kinase (ALK) V. Thrombin stimulated elongation of GAG chains and increased proteoglycan core protein expression and these responses were blocked by the TbetaRI antagonist, SB431542 and TbetaRI siRNA knockdown, as well as several protease-activated receptor (PAR)-1 antagonists. The canonical downstream response to TGF-beta is increased C-terminal phosphorylation of the transcription factor Smad2 generating phospho-Smad2C (phosphorylation of Smad2 C-terminal region). Thrombin stimulated increased phospho-Smad2C levels, and the response was blocked by SB431542 and JNJ5177094. The proteolytically inactive thrombin mimetic thrombin-receptor activating peptide also stimulated an increase in cytosolic phospho-Smad2C. Signaling pathways for growth factor regulated proteoglycan synthesis represent therapeutic targets for the prevention of atherosclerosis, but the novel finding of a GPCR-mediated transactivation of a serine/threonine growth factor receptor almost certainly has implications well beyond the synthesis of proteoglycans. PMID- 20571026 TI - Pyruvate formate-lyase, evidence for an open conformation favored in the presence of its activating enzyme. AB - Pyruvate formate-lyase-activating enzyme (PFL-AE) activates pyruvate formate lyase (PFL) by generating a catalytically essential radical on Gly-734 of PFL. Crystal structures of unactivated PFL reveal that Gly-734 is buried 8 A from the surface of the protein in what we refer to here as the closed conformation of PFL. We provide here the first experimental evidence for an alternate open conformation of PFL in which: (i) the glycyl radical is significantly less stable; (ii) the activated enzyme exhibits lower catalytic activity; (iii) the glycyl radical undergoes less H/D exchange with solvent; and (iv) the T(m) of the protein is decreased. The evidence suggests that in the open conformation of PFL, the Gly-734 residue is located not in its buried position in the enzyme active site but rather in a more solvent-exposed location. Further, we find that the presence of the PFL-AE increases the proportion of PFL in the open conformation; this observation supports the idea that PFL-AE accesses Gly-734 for direct hydrogen atom abstraction by binding to the Gly-734 loop in the open conformation, thereby shifting the closed <--> open equilibrium of PFL to the right. Together, our results lead to a model in which PFL can exist in either a closed conformation, with Gly-734 buried in the active site of PFL and harboring a stable glycyl radical, or an open conformation, with Gly-734 more solvent exposed and accessible to the PFL-AE active site. The equilibrium between these two conformations of PFL is modulated by the interaction with PFL-AE. PMID- 20571027 TI - Mechanism of regulation of bcl-2 mRNA by nucleolin and A+U-rich element-binding factor 1 (AUF1). AB - The antiapoptotic Bcl-2 protein is overexpressed in a variety of cancers, particularly leukemias. In some cell types this is the result of enhanced stability of bcl-2 mRNA, which is controlled by elements in its 3'-untranslated region. Nucleolin is one of the proteins that binds to bcl-2 mRNA, thereby increasing its half-life. Here, we examined the site on the bcl-2 3'-untranslated region that is bound by nucleolin as well as the protein binding domains important for bcl-2 mRNA recognition. RNase footprinting and RNA fragment binding assays demonstrated that nucleolin binds to a 40-nucleotide region at the 5' end of the 136-nucleotide bcl-2 AU-rich element (ARE(bcl-2)). The first two RNA binding domains of nucleolin were sufficient for high affinity binding to ARE(bcl 2). In RNA decay assays, ARE(bcl-2) transcripts were protected from exosomal decay by the addition of nucleolin. AUF1 has been shown to recruit the exosome to mRNAs. When MV-4-11 cell extracts were immunodepleted of AUF1, the rate of decay of ARE(bcl-2) transcripts was reduced, indicating that nucleolin and AUF1 have opposing roles in bcl-2 mRNA turnover. When the function of nucleolin in MV-4-11 cells was impaired by treatment with the nucleolin-targeting aptamer AS1411, association of AUF1 with bcl-2 mRNA was increased. This suggests that the degradation of bcl-2 mRNA induced by AS1411 results from both interference with nucleolin protection of bcl-2 mRNA and recruitment of the exosome by AUF1. Based on our findings, we propose a model that illustrates the opposing roles of nucleolin and AUF1 in regulating bcl-2 mRNA stability. PMID- 20571028 TI - Oleate inhibits steryl ester synthesis and causes liposensitivity in yeast. AB - In the yeast Saccharomyces cerevisiae, neutral lipids can be synthesized by four acyltransferases, namely Dga1p and Lro1p producing triacylglycerols (TAG) and Are1p and Are2p forming steryl esters (SE). TAG and SE are stored in an organelle called lipid particles/droplet. Growth of yeast cells on oleate-supplemented media strongly induced proliferation of lipid particles and specifically the synthesis of TAG, which serve as the major pool for the excess of fatty acids. Surprisingly, SE synthesis was strongly inhibited under these conditions. Here, we show that this effect was not due to decreased expression of ARE2 encoding the major yeast SE synthase at the transcriptional level but to competitive enzymatic inhibition of Are2p by free oleate. Consequently, a triple mutant dga1Deltalro1Deltaare1DeltaARE2(+) grown on oleate did not form substantial amounts of SE and exhibited a growth phenotype similar to the dga1Deltalro1Deltaare1Deltaare2Delta quadruple mutant, including lack of lipid particles. Growth of these mutants on oleate was strongly delayed, and cell viability was decreased but rescued by adaptation. In these strains, oleate stress caused morphological changes of intracellular membranes, altered phospholipid composition and formation of an additional lipid class, ethyl esters of fatty acids. In summary, our data showed that exposure to oleate led to disturbed lipid and membrane homeostasis along with liposensitivity of the yeast. PMID- 20571029 TI - Phenethyl isothiocyanate inhibits oxidative phosphorylation to trigger reactive oxygen species-mediated death of human prostate cancer cells. AB - Phenethyl isothiocyanate (PEITC), a constituent of edible cruciferous vegetables such as watercress, not only affords significant protection against chemically induced cancer in experimental rodents but also inhibits growth of human cancer cells by causing apoptotic and autophagic cell death. However, the underlying mechanism of PEITC-induced cell death is not fully understood. Using LNCaP and PC 3 human prostate cancer cells as a model, we demonstrate that the PEITC-induced cell death is initiated by production of reactive oxygen species (ROS) resulting from inhibition of oxidative phosphorylation (OXPHOS). Exposure of LNCaP and PC-3 cells to pharmacologic concentrations of PEITC resulted in ROS production, which correlated with inhibition of complex III activity, suppression of OXPHOS, and ATP depletion. These effects were not observed in a representative normal human prostate epithelial cell line (PrEC). The ROS production by PEITC treatment was not influenced by cyclosporin A. The Rho-0 variants of LNCaP and PC-3 cells were more resistant to PEITC-mediated ROS generation, apoptotic DNA fragmentation, and collapse of mitochondrial membrane potential compared with respective wild-type cells. The PEITC treatment resulted in activation of Bax in wild-type LNCaP and PC-3 cells, but not in their respective Rho-0 variants. Furthermore, RNA interference of Bax and Bak conferred significant protection against PEITC induced apoptosis. The Rho-0 variants of LNCaP and PC-3 cells also resisted PEITC mediated autophagy. In conclusion, the present study provides novel insight into the molecular circuitry of PEITC-induced cell death involving ROS production due to inhibition of complex III and OXPHOS. PMID- 20571030 TI - Iron-mediated oxidation induces conformational changes within the redox-sensing protein HbpS. AB - HbpS is an extracellular oligomeric protein, which has been shown to act in concert with the two-component system SenS-SenR during the sensing of redox stress. HbpS can bind and degrade heme under oxidative stress conditions, leading to a free iron ion. The liberated iron is subsequently coordinated on the protein surface. Furthermore, HbpS has been shown to modulate the phosphorylation state of the sensor kinase SenS as, in the absence of oxidative stress conditions, HbpS inhibits SenS autophosphorylation whereas the presence of heme or iron ions and redox-stressing agents enhances it. Using HbpS wild type and mutants as well as different biochemical and biophysical approaches, we show that iron-mediated oxidative stress induces both secondary structure and overall intrinsic conformational changes within HbpS. We demonstrate in addition that HbpS is oxidatively modified, leading to the generation of highly reactive carbonyl groups and tyrosine-tyrosine bonds. Further examination of the crystal structure and subsequent mutational analyses allowed the identification of the tyrosine residue participating in dityrosine formation, which occurs between two monomers within the octomeric assembly. Therefore, it is proposed that oxidative modifications causing structural and conformational changes are responsible for the control of SenS and hence of the HbpS-SenS-SenR signaling cascade. PMID- 20571031 TI - Stage-specific control of connective tissue growth factor (CTGF/CCN2) expression in chondrocytes by Sox9 and beta-catenin. AB - CCN2/connective tissue growth factor is highly expressed in hypertrophic chondrocytes and is required for chondrogenesis. However, the transcriptional mechanisms controlling its expression in cartilage are largely unknown. The activity of the Ccn2 promoter was, therefore, investigated in osteochondro progenitor cells and hypertrophic chondrocytes to ascertain these mechanisms. Sox9 and T-cell factor (TCF) x lymphoid enhancer factor (LEF) factors contain HMG domains and bind to related consensus sites. TCF x LEF factors are normally repressive but when bound to DNA in a complex with beta-catenin become activators of gene expression. In silico analysis of the Ccn2 proximal promoter identified multiple consensus TCF x LEF elements, one of which was also a consensus binding site for Sox9. Using luciferase reporter constructs, the TCF x LEF x Sox9 site was found to be involved in stage-specific expression of Ccn2. Luciferase, electrophoretic mobility shift assay (EMSA), and ChIP analysis revealed that Sox9 represses Ccn2 expression by binding to the consensus TCF x LEF x Sox9 site. On the other hand, the same assays showed that in hypertrophic chondrocytes, TCF x LEF x beta-catenin complexes occupy the consensus TCF x LEF x Sox9 site and activate Ccn2 expression. Furthermore, transgenic mice in which lacZ expression is driven under the control of the proximal Ccn2 promoter revealed that the proximal Ccn2 promoter responded to Wnt signaling in cartilage. Hence, we propose that differential occupancy of the TCF x LEF x Sox9 site by Sox9 versus beta catenin restricts high levels of Ccn2 expression to hypertrophic chondrocytes. PMID- 20571032 TI - Cooperativity between the phosphorylation of Thr95 and Ser77 of NHERF-1 in the hormonal regulation of renal phosphate transport. AB - The phosphorylation of the sodium-hydrogen exchanger regulatory factor-1 (NHERF 1) plays a key role in the regulation of renal phosphate transport by parathyroid hormone (PTH) and dopamine. Ser(77) in the first PDZ domain of NHERF-1 is a downstream target of both hormones. The current experiments explore the role of Thr(95), another phosphate acceptor site in the PDZ I domain, on hormone-mediated regulation of phosphate transport in the proximal tubule of the kidney. The substitution of alanine for threonine at position 95 (T95A) significantly decreased the rate and extent of in vitro phosphorylation of Ser(77) by PKC. In NHERF-1-null proximal tubule cells, neither PTH nor dopamine inhibited sodium dependent phosphate transport. Infection of the cells with adenovirus expressing full-length WT GFP-NHERF-1 increased basal phosphate transport and restored the inhibitory effect of both PTH and dopamine. Infection with full-length NHERF-1 containing a T95A mutation, however, increased basal phosphate transport but not the responsiveness to either hormone. As determined by surface plasmon resonance, the substitution of serine for aspartic acid (S77D) in the PDZ I domain decreased the binding affinity to the sodium-dependent phosphate transporter 2a (Npt2a) as compared with WT PDZ I, but a T95D mutation had no effect on binding. Finally, cellular studies indicated that both PTH and dopamine treatment increased the phosphorylation of Thr(95). These studies indicate a remarkable cooperativity between the phosphorylation of Thr(95) and Ser(77) of NHERF-1 in the hormonal regulation of renal phosphate transport. The phosphorylation of Thr(95) facilitates the phosphorylation of Ser(77). This, in turn, results in the dissociation of NHERF-1 from Npt2a and a decrease in phosphate transport in renal proximal tubule cells. PMID- 20571033 TI - Insulin induces swelling-dependent activation of the epidermal growth factor receptor in rat liver. AB - The aim of the study was to analyze whether the proliferative effects of insulin in rat liver involve cross-signaling toward the epidermal growth factor receptor (EGFR) and whether this is mediated by insulin-induced hepatocyte swelling. Studies were performed in the perfused rat liver and in primary rat hepatocytes. Insulin (35 nmol/liter) induced phosphorylation of the EGFR at position Tyr(845) and Tyr(1173), but not at Tyr(1045), suggesting that EGF is not involved in insulin-induced EGFR activation. Insulin-induced EGFR phosphorylation and subsequent ERK1/2 phosphorylation were sensitive to bumetanide, indicating an involvement of insulin-induced hepatocyte swelling. In line with this, hypoosmotic (225 mosmol/liter) hepatocyte swelling also induced EGFR and ERK1/2 activation. Insulin- and hypoosmolarity-induced EGFR activation were sensitive to inhibition by an integrin-antagonistic RGD peptide, an integrin beta1 subtype blocking antibody, and the c-Src inhibitor PP-2, indicating the involvement of the recently described integrin-dependent osmosensing/signaling pathway (Schliess, F., Reissmann, R., Reinehr, R., vom Dahl, S., and Haussinger, D. (2004) J. Biol. Chem. 279, 21294-21301). As shown by immunoprecipitation studies, insulin and hypoosmolarity induced a rapid, RGD peptide-, integrin beta1-blocking antibody and PP-2-sensitive association of c-Src with the EGFR. As for control, insulin-induced insulin receptor substrate-1 phosphorylation remained unaffected by the RGD peptide, PP-2, or inhibition of the EGFR tyrosine kinase activity by AG1478. Both insulin and hypoosmolarity induced a significant increase in BrdU uptake in primary rat hepatocytes, which was sensitive to RGD peptide-, integrin beta1-blocking antibody, PP-2, AG1478, and PD098059. It is concluded that insulin or hypoosmolarity-induced hepatocyte swelling triggers an integrin- and c-Src kinase-dependent EGFR activation, which may explain the proliferative effects of insulin. PMID- 20571034 TI - Do drug transporter (ABCB1) SNPs influence cyclosporine and tacrolimus dose requirements and renal allograft outcome in the posttransplantation period? AB - Polymorphisms in the drug transporter gene (ABCB1) may play a significant role in individualizing cyclosporine (CsA) and tacrolimus (Tac) dosage and subsequently the allograft outcome in renal transplant recipients. In total, 225 recipients on CsA and 75 on Tac-based immunosuppression regimen were recruited, and 6 common polymorphic sites in the ABCB1 gene were analyzed for association with dose adjusted levels of CsA/Tac. Furthermore, association of ABCB1 single-nucleotide polymorphisms (SNPs) with allograft outcome was examined. GG and CC genotype patients at ABCB1 2677G>T and ABCB1 3435C>T were associated with lower dose adjusted levels of CsA and Tac at 1 month (P = .057, P = .034), 3 months (P = .001, P = .015), and 6 months (P = .043) posttransplantation. Wild-type patients at 1236C>T (log P = .025) and 2677G>T (log P = .002) in CsA and 2677G>T (log P = .008) and 3435C>T (log P = .015) in Tac therapy patients demonstrated lower mean time to allograft rejection. No influence of ABCB1 haplotypes on CsA/Tac dose adjusted levels was observed. Wild-type patients at ABCB1 2677G>T and 3435C>T were associated with lower dose-adjusted levels and thereby were at increased risk of allograft rejection because of under-immunosuppression in the early part of posttransplantation. Thus, genetic evaluation may be helpful to identify patients at risk for allograft rejection and also to individualize immunosuppressant dosing. PMID- 20571035 TI - Mining the surface proteome of tomato (Solanum lycopersicum) fruit for proteins associated with cuticle biogenesis. AB - The aerial organs of plants are covered by the cuticle, a polyester matrix of cutin and organic solvent-soluble waxes that is contiguous with the polysaccharide cell wall of the epidermis. The cuticle is an important surface barrier between a plant and its environment, providing protection against desiccation, disease, and pests. However, many aspects of the mechanisms of cuticle biosynthesis, assembly, and restructuring are entirely unknown. To identify candidate proteins with a role in cuticle biogenesis, a surface protein extract was obtained from tomato (Solanum lycopersicum) fruits by dipping in an organic solvent and the constituent proteins were identified by several complementary fractionation strategies and two mass spectrometry techniques. Of the approximately 200 proteins that were identified, a subset is potentially involved in the transport, deposition, or modification of the cuticle, such as those with predicted lipid-associated protein domains. These include several lipid-transfer proteins, GDSL-motif lipase/hydrolase family proteins, and an MD-2 related lipid recognition domain-containing protein. The epidermal-specific transcript accumulation of several of these candidates was confirmed by laser capture microdissection and quantitative reverse transcription-PCR (qRT-PCR), together with their expression during various stages of fruit development. This indicated a complex pattern of cuticle deposition, and models for cuticle biogenesis and restructuring are discussed. PMID- 20571036 TI - Loss of TRPC1-mediated Ca2+ influx contributes to impaired degranulation in Fyn deficient mouse bone marrow-derived mast cells. AB - MC degranulation requires the influx of calcium from the extracellular environment. Orai1/STIM1 is essential to MC SOCE, as shown in rat peritoneal MCs, the rat MC lines (RBL-2H3), or in Orai1 null embryo liver-derived, cultured MCs. However, minimal information exists about the role of other calcium channels expressed on these cells. Here, we demonstrate that the nonselective TRPC1 participates in FcepsilonRI-mediated calcium entry in mouse BMMCs. We found that Fyn null MCs, which have an impaired degranulation response, expressed reduced levels of TRPC1, had normal depletion of intracellular calcium stores but an impaired calcium influx, and failed to depolymerize cortical F-actin (a key step for granule-plasma membrane fusion). Partial RNAi silencing of TRPC1 expression in WT MCs (to the level of Fyn null MCs) mimicked the Fyn null defect in calcium influx, cortical F-actin depolymerization, and MC degranulation. Ectopic expression of Fyn or TRPC1 in Fyn null MCs restored calcium responses and cortical F-actin depolymerization and increased MC degranulation. Together with our findings that expression of Orai1 is not altered in Fyn null MCs, our findings suggest that TRPC1 participates in calcium influx and other key events required for MC degranulation. This demonstrates that in addition to a role described previously for Orai1 in promoting MC degranulation, nonselective cation channels participate in promoting the exocytotic response. PMID- 20571038 TI - Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage. AB - PURPOSE: The contribution of axonal injury to brain damage after aneurysmal subarachnoid haemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesised that patients with aSAH would have elevated cerebrospinal fluid (CSF) NF-L levels and sought to explore the clinical correlates of CSF NF-L dynamics. METHODS: Serial ventricular CSF (vCSF) samples were collected from 35 patients with aSAH for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analysed in relation to acute clinical status, radiological findings and 6-month outcomes. RESULTS: vCSF NF-L concentrations were elevated in all patients with aSAH. Patients with early cerebral ischaemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial haemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischaemia or 6-month Glasgow Outcome Scale. CONCLUSIONS: Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with ECI. However, our results suggest that axonal injury after aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long-term clinical outcomes. PMID- 20571037 TI - Adaptor protein Lnk inhibits c-Fms-mediated macrophage function. AB - The M-CSFR (c-Fms) participates in proliferation, differentiation, and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M-CSF results in phosphorylation of tyrosine residues on c-Fms, thereby creating binding sites for molecules containing SH2 domains. Lnk is a SH2 domain adaptor protein that negatively regulates hematopoietic cytokine receptors. Here, we show that Lnk binds to c Fms. Biological and functional effects of this interaction were examined in macrophages from Lnk-deficient (KO) and WT mice. Clonogenic assays demonstrated an elevated number of M-CFUs in the bone marrow of Lnk KO mice. Furthermore, the M-CSF-induced phosphorylation of Akt in Lnk KO macrophages was increased and prolonged, whereas phosphorylation of Erk was diminished. Zymosan-stimulated production of ROS was increased dramatically in a M-CSF-dependent manner in Lnk KO macrophages. Lastly, Lnk inhibited M-CSF-induced migration of macrophages. In summary, we show that Lnk binds to c-Fms and can blunt M-CSF stimulation. Modulation of levels of Lnk in macrophages may provide a unique therapeutic approach to increase innate host defenses. PMID- 20571039 TI - The estimated life expectancy in a community cohort of Parkinson's disease patients with and without dementia, compared with the UK population. AB - OBJECTIVE: To compare survival, life expectancies (LE), and the anticipated age at the time of death (AAD), in a community-based cohort of Parkinson's disease (PD) patients with and without significant cognitive impairment, with an age sex matched population of England and Wales. METHODS: The age- and sex-specific standardised mortality ratios (SMR) were calculated and stratified by dementia status. The LE and AAD estimations were calculated from the SMRs of the 2003 UK population, using a modified Gompertz function. RESULTS: In total, 166 PD patients participated in the investigation, of which 91 died by the 4-year follow up. The overall SMR was 2.09 (95% CI 1.68 to 2.57). Demented patients had significantly higher SMRs than non-demented patients (SMR 3.10, 95% CI 2.39 to 3.96 vs SMR 1.15, 95% CI 0.75 to 1.69, p<0.001). In our cohort, the LE in younger onset demented patients (55-74 years) was much lower than in non-demented patients (7.5; SD 3 vs 12.4; SD 7). Likewise, the estimated AAD in younger onset patients with dementia was also much lower (demented 72.4; SD 4 vs not demented 77.8; SD 7). In older-onset patients with dementia (>75 years), the differences in LE (demented 2.1; SD 1 vs not demented 4.7; SD 4) and AAD were less apparent (demented 89.5; SD 6 vs not demented 92.2; SD 6). CONCLUSION: The survival, LE and AAD in patients with PD are much lower compared with the general population, apart from those patients who do not develop dementia, who appear to have near normal population mortalities. However, dementia and younger onset of PD appear to be important determinants of survival, LE and AAD. PMID- 20571040 TI - Long-term beta interferon in MS: safe, but what effect on disability? PMID- 20571041 TI - MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity. PMID- 20571042 TI - Neurological picture. Pseudoperipheral tongue weakness. PMID- 20571043 TI - Myopathies caused by homozygous titin mutations: limb-girdle muscular dystrophy 2J and variations of phenotype. AB - Limb-girdle muscular dystrophy 2J caused by mutations in C-terminal titin has so far been identified in Finnish patients only. This may in part be due to limited availability of diagnostic tests for titin defects. In this report, a French family with an autosomal-dominant late-onset distal myopathy of the tibial muscular dystrophy phenotype segregating in several members of the family was described. One deceased patient in the family proved to be homozygous for the C terminal truncating titin mutation because of consanguinity. According to available medical records, the patient had a clearly more severe generalised muscle weakness and atrophy phenotype not recognised as a distal myopathy at the time. Autopsy findings in one of the original Finnish limb-girdle muscular dystrophy 2J patients were reported and the early phenotype in a newly identified young patient with homozygous Finnish C-terminal titin mutation (FINmaj) was detailed. PMID- 20571044 TI - Frequencies of LRRK2 variants in Thai patients with Parkinson's disease: evidence for an R1628P founder. PMID- 20571045 TI - "Alice in Wonderland syndrome" associated with topiramate for migraine prevention. AB - Various visual and sensory phenomena have been described in migraine with aura. Among those, the 'Alice in Wonderland' syndrome is defined as a distortion of the body image with the patient being aware of its unreal nature. Here, the case of a 17-year-old girl with migraine without aura who developed an 'Alice in Wonderland' syndrome repeatedly on topiramate treatment was presented and potential pathophysiological concepts were discussed. PMID- 20571046 TI - The phenotype spectrum of Japanese multiple system atrophy. AB - OBJECTIVE: This study aimed to determine the spectrum of pathological involvement of the striatonigral (StrN) and olivopontocerebellar (OPC) systems in Japanese patients with multiple system atrophy (MSA). This study also aimed to compare the pathological spectrum of Japanese MSA patients with the previously reported results in British MSA patients. METHODS: A semiquantitative pathological analysis of 50 MSA patients' brains that were referred to the Brain Research Institute, Niigata University, Japan, was performed. The severity of neuronal cell loss was determined as previously described by the study from the Queen Square Brain Bank (QSBB), UK. RESULTS: The mean neuronal cell loss score was significantly higher in the OPC area than in the basal ganglia sites examined, except the dorsolateral putamen. The relative prevalence of pathological phenotypes showed that 40% of cases had OPC-predominant pathology, 18% had StrN predominant pathology and the remaining (42%) had equivalent StrN and OPC pathology. None of the MSA cases had coexistent Lewy bodies in the dorsal motor nucleus of the vagus and the substantia nigra. CONCLUSIONS: In contrast to the previously reported results involving British patients' brains from the QSBB (OPC predominant pathology 17%, StrN-predominant pathology 34%, equivalent StrN and OPC pathology 49%), the results of the present study showed more pathological involvement of the OPC system than of the StrN system. The rarity of Lewy bodies may underlie the phenotypic expression of Japanese MSA. The present observations reflect the disequilibrium in the phenotype distribution between the two populations. PMID- 20571047 TI - Neurological picture. Bilateral facial nerve palsy associated with Epstein-Barr virus infection. PMID- 20571048 TI - Seizure freedom following 49 years of refractory epilepsy due to focal cortical dysplasia. PMID- 20571049 TI - Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration. AB - Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione reductase-dependent routes are poor at supporting DNA replication in these organisms. We have studied proliferation of thioredoxin-reductase-1 (Txnrd1) deficient hepatocytes in mice. During development and regeneration, normal mice and mice having Txnrd1-deficient hepatocytes exhibited similar liver growth rates. Proportions of hepatocytes that immunostained for PCNA, phosphohistone H3 or incorporated BrdU were also similar, indicating livers of either genotype had similar levels of proliferative, S and M phase hepatocytes, respectively. Replication was blocked by hydroxyurea, confirming that RNR activity was required by Txnrd1-deficient hepatocytes. Regenerative thymidine incorporation was similar in normal and Txnrd1-deficient livers, further indicating that DNA synthesis was unaffected. Using genetic chimeras in which a fluorescently marked subset of hepatocytes was Txnrd1-deficient while others were not, we found that the multigenerational contributions of both hepatocyte types to development and to liver regeneration were indistinguishable. We conclude that, in mouse hepatocytes, a Txnrd1-independent route for the supply of electrons to RNR can fully support DNA replication and normal proliferative growth. PMID- 20571050 TI - Myoferlin regulation by NFAT in muscle injury, regeneration and repair. AB - Ferlin proteins mediate membrane-fusion events in response to Ca(2+). Myoferlin, a member of the ferlin family, is required for normal muscle development, during which it mediates myoblast fusion. We isolated both damaged and intact myofibers from a mouse model of muscular dystrophy using laser-capture microdissection and found that the levels of myoferlin mRNA and protein were increased in damaged myofibers. To better define the components of the muscle-injury response, we identified a discreet 1543-bp fragment of the myoferlin promoter, containing multiple NFAT-binding sites, and found that this was sufficient to drive high level myoferlin expression in cells and in vivo. This promoter recapitulated normal myoferlin expression in that it was downregulated in healthy myofibers and was upregulated in response to myofiber damage. Transgenic mice expressing GFP under the control of the myoferlin promoter were generated and GFP expression in this model was used to track muscle damage in vivo after muscle injury and in muscle disease. Myoferlin modulates the response to muscle injury through its activity in both myoblasts and mature myofibers. PMID- 20571051 TI - MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. AB - Tight control of p63 protein levels must be achieved under differentiation or apoptotic conditions. Here, we describe a new regulatory pathway for the DeltaNp63alpha protein. We found that MDM2 binds DeltaNp63alpha in the nucleus promoting its translocation to the cytoplasm. The MDM2 nuclear localization signal is required for DeltaNp63alpha nuclear export and subsequent degradation, whereas the MDM2 ring-finger domain is dispensable. Once exported to the cytoplasm by MDM2, p63 is targeted for degradation by the Fbw7 E3-ubiquitin ligase. Efficient degradation of DeltaNp63alpha by Fbw7 (also known as FBXW7) requires GSK3 kinase activity. By deletion and point mutations analysis we have identified a phosphodegron located in the alpha and beta tail of p63 that is required for degradation. Furthermore, we show that MDM2 or Fbw7 depletion inhibits degradation of endogenous DeltaNp63alpha in cells exposed to UV irradiation, adriamycin and upon keratinocyte differentiation. Our findings suggest that following DNA damage and cellular differentiation MDM2 and Fbw7 can cooperate to regulate the levels of the pro-proliferative DeltaNp63alpha protein. PMID- 20571052 TI - Transmembrane-domain determinants for SNARE-mediated membrane fusion. AB - Neurosecretion involves fusion of vesicles with the plasma membrane. Such membrane fusion is mediated by the SNARE complex, which is composed of the vesicle-associated protein synaptobrevin (VAMP2), and the plasma membrane proteins syntaxin-1A and SNAP-25. Although clearly important at the point of membrane fusion, the precise structural and functional requirements for the transmembrane domains (TMDs) of SNAREs in bringing about neurosecretion remain largely unknown. Here, we used a bimolecular fluorescence complementation (BiFC) approach to study SNARE protein interactions involving TMDs in vivo. VAMP2 molecules were found to dimerise through their TMDs in intact cells. Dimerisation was abolished when replacing a glycine residue in the centre of the TMD with residues of increasing molecular volume. However, such mutations still were fully competent in bringing about membrane-fusion events, suggesting that dimerisation of the VAMP2 TMDs does not have an important functional role. By contrast, a series of deletion or insertion mutants in the C-terminal half of the TMD were largely deficient in supporting neurosecretion, whereas mutations in the N terminal half did not display severe secretory deficits. Thus, structural length requirements, largely confined to the C-terminal half of the VAMP2 TMD, seem to be essential for SNARE-mediated membrane-fusion events in cells. PMID- 20571053 TI - Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy. AB - MicroRNAs are involved in several aspects of cardiac hypertrophy, including cardiac growth, conduction, and fibrosis. However, their effects on the regulation of the cardiomyocyte cytoskeleton in this pathological process are not known. Here, with microRNA microarray and small RNA library sequencing, we show that microRNA-1 (miR-1) is the most abundant microRNA in the human heart. By applying bioinformatic target prediction, a cytoskeleton regulatory protein twinfilin-1 was identified as a potential target of miR-1. Overexpression of miR 1 not only reduced the luciferase activity of the reporter containing the 3' untranslated region of twinfilin-1 mRNA, but also suppressed the endogenous protein expression of twinfilin-1, indicating that twinfilin-1 is a direct target of miR-1. miR-1 was substantially downregulated in the rat hypertrophic left ventricle and phenylephrine-induced hypertrophic cardiomyocytes, and accordingly, the protein level of twinfilin-1 was increased. Furthermore, overexpression of miR-1 in hypertrophic cardiomyocytes reduced the cell size and attenuated the expression of hypertrophic markers, whereas silencing of miR-1 in cardiomyocytes resulted in the hypertrophic phenotype. In accordance, twinfilin-1 overexpression promoted cardiomyocyte hypertrophy. Taken together, our results demonstrate that the cytoskeleton regulatory protein twinfilin-1 is a novel target of miR-1, and that reduction of miR-1 by hypertrophic stimuli induces the upregulation of twinfilin-1, which in turn evokes hypertrophy through the regulation of cardiac cytoskeleton. PMID- 20571054 TI - NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acid. AB - The epithelial brush border (BB) Na(+)/H(+) exchanger NHE3 is associated with the actin cytoskeleton by binding both directly and indirectly to ezrin; indirect binding is via attachment to NHERF family proteins. NHE3 mobility in polarized epithelial cell BBs is restricted by the actin cytoskeleton and NHERF binding such that only approximately 30% of NHE3 in the apical domain of an OK cell line stably expressing NHERF2 is mobile, as judged by FRAP analysis. Given that levels of NHE3 are partially regulated by changes in trafficking, we investigated whether the cytoskeleton association of NHE3 was dynamic and changed as part of acute regulation to allow NHE3 trafficking. The agonist studied was lysophosphatidic acid (LPA), an inflammatory mediator, which acutely stimulates NHE3 activity by increasing the amount of NHE3 on the BBs by stimulated exocytosis. LPA acutely stimulated NHE3 activity in OK cells stably expressing NHERF2. Two conditions that totally prevented LPA stimulation of NHE3 activity only partially prevented stimulation of NHE3 mobility: the phosphoinositide 3 kinase (PI3K) inhibitor LY294002, and the NHE3F1 double mutant which has minimal direct binding of NHE3 to ezrin. These results show that LPA stimulation of NHE3 mobility occurs in two parts: (1) PI3K-dependent exocytic trafficking to the BB and (2) an increase in surface mobility of NHE3 in BBs under basal conditions. Moreover, the LPA stimulatory effect on NHE3 mobility required NHERF2. Although NHE3 and NHERF2 co-precipitated under basal conditions, they failed to co precipitate 30 minutes after addition of LPA, whereas the physical association was re-established by 50-60 minutes. This dynamic interaction between NHERF2 and NHE3 was confirmed by acceptor photobleaching Forster Resonance energy Transfer (FRET). The restricted mobility of NHE3 in BBs under basal conditions as a result of cytoskeleton association is therefore dynamic and is reversed as part of acute LPA stimulation of NHE3. We suggest that this acute but transient increase in NHE3 mobility induced by LPA occurs via two processes: addition of NHE3 to the BB by exocytosis, a process which precedes binding of NHE3 to the actin cytoskeleton via NHERF2-ezrin, and by release of NHERF2 from the NHE3 already localized in the apical membrane, enabling NHE3 to distribute throughout the microvilli. These fractions of NHE3 make up a newly identified pool of NHE3 called the 'transit pool'. Moreover, our results show that there are two aspects of LPA signaling involved in stimulation of NHE3 activity: PI3K-dependent stimulated NHE3 exocytosis and the newly described, PI3K-independent dissociation of microvillar NHE3 from NHERF2. PMID- 20571055 TI - Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin. AB - Sortilin, also known as neurotensin receptor 3 (NTR3), is a transmembrane protein with a dual function. It acts as a receptor for neuromediators and growth factors at the plasma membrane, but it has also been implicated in binding and transport of some lysosomal proteins. However, the role of sortilin during phagosome maturation has not been investigated before. Here, we show that in macrophages, sortilin is mainly localized in the Golgi and transported to latex-bead phagosomes (LBPs). Using live-cell imaging and electron microscopy, we found that sortilin is delivered to LBPs in a manner that depends on its cytoplasmic tail. We also show that sortilin participates in the direct delivery of acid sphingomyelinase (ASM) and prosaposin (PS) to the phagosome, bypassing fusion with lysosomal compartments. Further analysis confirmed that ASM and PS are targeted to the phagosome by sortilin in a Brefeldin-A-sensitive pathway. Analysis of primary macrophages isolated from Sort1(-/-) mice indicated that the delivery of ASM and PS, but not pro-cathepsin D, to LBPs was severely impaired. We propose a pathway mediated by sortilin by which selected lysosomal proteins are transported to the phagosome along a Golgi-dependent route during the maturation of phagosomes. PMID- 20571059 TI - Reversal of TNP-470-induced endothelial cell growth arrest by guanine and guanine nucleosides. AB - The mechanism of action of TNP-470 [O-(chloroacetyl-carbamoyl) fumagillol], which potently and selectively inhibits the proliferation of endothelial cells, is incompletely understood. Previous studies have established its binding protein and the most distal effector of its growth arrest activity as methionine aminopeptidase 2 (MetAP-2) and p21(WAF1/CIP1), respectively. However, the mechanistic steps between these two effectors have not been identified. We have found that addition of exogenous guanine and guanine-containing nucleosides to culture medium will completely reverse the cytostatic effect of TNP-470 on both cultured bovine aortic and mouse pulmonary endothelial cells. Western blotting showed that supplementation with exogenous guanosine reverses the induction of p21(WAF1/CIP1) by TNP-470. This "rescue" by guanine/guanosine was abolished when the guanine salvage pathway of nucleotide biosynthesis was inhibited with Immucillin H, suggesting that TNP-470 might reduce de novo guanine synthesis in endothelial cells. However, an analysis of inosine 5'-monophosphate dehydrogenase, the rate-limiting enzyme in de novo guanine synthesis and target of the antiangiogenic drug mycophenolic acid, showed no TNP-470-induced changes. Curiously, quantitation of cellular nucleotides confirmed that GTP levels were not reduced after TNP-470 treatment. Addition of guanosine at the start of G(1) phase causes a doubling in GTP levels that persists to the G(1)/S phase transition, where commitment to TNP-470 growth arrest occurs. Thus, guanine rescue involves an augmentation of cellular GTP beyond physiological levels rather than a restoration of a drug-induced GTP deficit. Determining the mechanism whereby this causes restoration of endothelial cell proliferation is an ongoing investigation. PMID- 20571060 TI - Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice. AB - The endocannabinoid system is involved in the regulation of gastrointestinal (GI) motility and inflammation. Using the peripherally restricted cannabinoid (CB)(1)/CB(2) receptor agonist naphthalen-1-yl-(4-pentyloxynaphthalen-1 yl)methanone (SAB378), we investigated the role of peripheral cannabinoid receptors in the regulation of GI motility and the development of colitis in mice. The actions of SAB378 on whole gut transit, upper GI transit, colonic propulsion, and locomotor activity were investigated in C57BL/6N, CB(1) receptor knockout, and CB(2) receptor knockout mice. The potential for SAB378 to modify inflammation was studied by using dextran sulfate sodium (DSS) and 2,4,6 trinitrobenzene sulfonic acid (TNBS) models of experimental colitis. SAB378 did not modify locomotor activity. SAB378 slowed all parameters of GI motility, and these effects were significantly reduced by the CB(1) receptor antagonist N (piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM251), but not by the CB(2) receptor antagonist 6-iodo-2-methyl-1 [2-(4-morpholinyl)ethyl]-1H- indol-3-yl](4-methoxyphenyl)methanone (AM630). SAB378 did not inhibit GI transit or colonic propulsion in CB(1) receptor knockout mice, whereas its effects were observed in CB(2) receptor knockout mice. SAB378 did not reduce the degree of colitis induced by DSS or TNBS. The actions of SAB378 on GI motility are mediated by peripherally located CB(1) receptors. SAB378 was not effective against two models of experimental colitis, which may indicate that peripheral cannabinoid receptor stimulation alone may not be sufficient to mediate the anti-inflammatory effects of cannabinoids. PMID- 20571061 TI - Sialic acid-focused quantitative mouse serum glycoproteomics by multiple reaction monitoring assay. AB - Despite increasing importance of protein glycosylation, most of the large-scale glycoproteomics have been limited to profiling the sites of N-glycosylation. However, in-depth knowledge of protein glycosylation to uncover functions and their clinical applications requires quantitative glycoproteomics eliciting both peptide and glycan sequences concurrently. Here we describe a novel strategy for the multiplexed quantitative mouse serum glycoproteomics based on a specific chemical ligation, namely, reverse glycoblotting technique, focusing sialic acids and multiple reaction monitoring (MRM). LC-MS/MS analysis of de-glycosylated peptides identified 270 mouse serum peptides (95 glycoproteins) as sialylated glycopeptides, of which 67 glycopeptides were fully characterized by MS/MS analyses in a straightforward manner. We revealed the importance of a fragment ion containing innermost N-acetylglucosamine (GlcNAc) residue as MRM transitions regardless the sequence of the peptides. Versatility of the reverse glycoblotting assisted MRM assays was demonstrated by quantitative comparison of 25 targeted glycopeptides from 16 proteins between mice with homo and hetero types of diabetes disease model. PMID- 20571062 TI - Combining the FLT3 inhibitor PKC412 and the triterpenoid CDDO-Me synergistically induces apoptosis in acute myeloid leukemia with the internal tandem duplication mutation. AB - Mutations of the FLT3 receptor tyrosine kinase consisting of internal tandem duplications (ITD) have been detected in blasts from 20% to 30% of patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. FLT3/ITD results in constitutive autophosphorylation of the receptor and factor independent survival in leukemia cell lines. The C-28 methyl ester of the oleane triterpenoid (CDDO-Me) is a multifunctional molecule that induces apoptosis of human myeloid leukemia cells. Here, we report that CDDO-Me blocks targeting of NFkappaB to the nucleus by inhibiting IkappaB kinase beta-mediated phosphorylation of IkappaBalpha. Moreover, CDDO-Me blocked constitutive activation of the signal transducer and activator of transcription 3. We report the potent and selective antiproliferative effects of CDDO-Me on FLT3/ITD positive myeloid leukemia cell lines and primary AML cells. The present studies show that CDDO-Me treatment results in caspase-3-mediated induction of apoptosis of FLT3/ITD-expressing cells and its antiproliferative effects are synergistic with PKC412, a FLT3-tyrosine kinase inhibitor currently in clinical trials. Taken together, our studies indicate that CDDO-Me greatly enhanced the efficacy of the FLT3 inhibitor PKC412, suggesting that combining two separate pathway inhibitors might be a viable therapeutic strategy for AML associated with a FLT3/ITD mutation. PMID- 20571063 TI - Targeting activating transcription factor 3 by Galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia. AB - Tyrosine kinase inhibitors (TKI) against Bcr-Abl are the first-line therapeutics for chronic myelogenous leukemia (CML). However, the resistance to Bcr-Abl TKIs is induced in leukemic cells not only by loss of sensitivity to TKIs through Bcr Abl-related molecular mechanisms but also by loss of addiction to Bcr-Abl TK activity by acquiring Bcr-Abl-unrelated additional oncogenic mutations. Therefore, the identification of an additional therapeutic target has been anticipated for achievement of a complete cure and to overcome resistance to treatment. We here showed that modified human Galectin-9 (hGal9), a lectin that show specific affinity for beta-galactosides, inhibits the proliferation of five CML-derived cell lines by inducing apoptosis at their IC(50)s from 17.5 to 164.9 nmol/L. Our study revealed that activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element binding protein family transcription factors, is the critical mediator for cell killing by hGal9, and that Noxa is one of the downstream effector molecules of ATF3. Bim, on the other hand, the BH3 only protein essential for apoptosis by Bcr-Abl TKIs, was not associated with hGal9-induced cell death. ATF3-mediated cell death by hGal9 was not hampered by the absence of p53, the presence of mutant Abl(T315I), or by P-glycoprotein overexpression. In addition, hGal9 showed the additive growth-inhibitory effect with imatinib on CML cell lines. Collectively, hGal9 is a candidate agent that may overcome various kinds of resistance to treatment for CML and may suggest that ATF3 may be a new target molecule for the development of new treatment modalities that can overcome resistance to currently available chemotherapeutics. PMID- 20571064 TI - The predominant WT1 isoform (+KTS) encodes a DNA-binding protein targeting the planar cell polarity gene Scribble in renal podocytes. AB - WT1 encodes a tumor suppressor first identified by its inactivation in Wilms' Tumor. Although one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three-amino acid (KTS) insertion. Using cells that conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning analysis to identify candidate WT1(+KTS)-regulated promoters. We identified the planar cell polarity gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33-nucleotide region within the Scribble promoter in mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway. PMID- 20571065 TI - Tissue inhibitor of metalloproteinase-2 regulates matrix metalloproteinase-2 mediated endothelial barrier dysfunction and breast cancer cell transmigration through lung microvascular endothelial cells. AB - Matrix metalloproteinases (MMP) have been implicated in multiple stages of cancer metastasis. Tissue inhibitor of metalloproteinase-2 (TIMP-2) plays an important role in regulating MMP-2 activity. By forming a ternary complex with pro-MMP-2 and its activator MMP-14 on the cell surface, TIMP-2 can either initiate or restrain the cleavage and subsequent activation of MMP-2. Our recent work has shown that breast cancer cell adhesion to vascular endothelial cells activates endothelial MMP-2, promoting tumor cell transendothelial migration (TEM(E)). However, the mechanism of MMP-2 regulation during TEM(E) remains unclear. In the current study, we present evidence that MMP-14 is expressed in both invasive breast cancer cells (MDA-MB-231 and MDA-MB-436) and lung microvascular endothelial cells (HBMVEC-L), whereas TIMP-2 is exclusively expressed and released from the cancer cells. The tumor cell-derived TIMP-2 was further identified as a major determinant of endothelial MMP-2 activity during tumor cell transmigration in the presence of MMP-14. This response was associated with endothelial barrier dysfunction because coculture of MDA-MB-231 or MDA-MB-436 with HBMVEC-L caused a significant decrease in transendothelial electrical resistance concomitantly with endothelial cell-cell junction disruption and tumor cell transmigration. Knockdown of TIMP-2 or inhibition of TIMP-2/MMP-14 attenuated MMP-2-dependent transendothelial electrical resistance response and TEM(E). These findings suggest a novel interactive role of breast cancer cells and vascular endothelial cells in regulating the TIMP-2/MMP-14/MMP-2 pathway during tumor metastasis. PMID- 20571066 TI - Telomerase as an important target of androgen signaling blockade for prostate cancer treatment. AB - As the mainstay treatment for advanced prostate cancer, androgen deprivation therapy (ADT) targets the action of androgen receptor (AR) by reducing androgen level and/or by using anti-androgen to compete with androgens for binding to AR. Albeit effective in extending survival, ADT is associated with dose-limiting toxicity and the development of castration-resistant prostate cancer (CRPC) after prolonged use. Because CRPC is lethal and incurable, developing effective strategies to enhance the efficacy of ADT and circumvent resistance becomes an urgent task. Continuous AR signaling constitutes one major mechanism underlying the development of CRPC. The present study showed that methylseleninic acid (MSA), an agent that effectively reduces AR abundance, could enhance the cancer killing efficacy of the anti-androgen bicalutamide in androgen-dependent and CRPC cells. We found that the combination of MSA and bicalutamide produced a robust downregulation of prostate-specific antigen and a recently identified AR target, telomerase, and its catalytic subunit, human telomerase reverse transcriptase. The downregulation of hTERT occurs mainly at the transcriptional level, and reduced AR occupancy of the promoter contributes to downregulation. Furthermore, apoptosis induction by the two agents is significantly mitigated by the restoration of hTERT. Our findings thus indicate that MSA in combination with anti-androgen could represent a viable approach to improve the therapeutic outcome of ADT. Given the critical role of hTERT/telomerase downregulation in mediating the combination effect and the fact that hTERT/telomerase could be measured in blood and urine, hTERT/telomerase could serve as an ideal tumor specific biomarker to monitor the efficacy of the combination therapy noninvasively. PMID- 20571067 TI - PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells. AB - Proteasome inhibitor PS-341 (also known as bortezomib) and histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for a variety of malignancies. In this study, we examined whether PS-341 and the HDAC inhibitor trichostatin A (TSA) induced apoptosis in head and neck squamous cell carcinoma (HNSCC), a common and lethal malignancy. We found that, although TSA treatment alone did not induce apoptosis in HNSCC cells, it significantly enhanced PS-341 induced apoptosis in HNSCC cells in vitro. Consistently, TSA significantly improved PS-341-mediated inhibition of HNSCC tumor growth in nude mice. Mechanistically, we found that TSA increased PS-341-induced Noxa expression and caspase activation in HNSCC cells. The knockdown of Noxa significantly reduced apoptosis induced by cotreatment of PS-341 and TSA. Taken together, our results provide new insight into the mechanisms of synergistic antitumor activity of the PS-341 and HDAC inhibitor regimen, offering a new therapeutic strategy for HNSCC patients. PMID- 20571068 TI - The dynamin inhibitors MiTMAB and OcTMAB induce cytokinesis failure and inhibit cell proliferation in human cancer cells. AB - The endocytic protein dynamin II (dynII) participates in cell cycle progression and has roles in centrosome cohesion and cytokinesis. We have described a series of small-molecule inhibitors of dynamin [myristyl trimethyl ammonium bromides (MiTMAB)] that competitively interfere with the ability of dynamin to bind phospholipids and prevent receptor-mediated endocytosis. We now report that dynII functions specifically during the abscission phase of cytokinesis and that MiTMABs exclusively block this step in the cell cycle. Cells treated with MiTMABs (MiTMAB and octadecyltrimethyl ammonium bromide) and dyn-depleted cells remain connected via an intracellular bridge for a prolonged period with an intact midbody ring before membrane regression and binucleate formation. MiTMABs are the first compounds reported to exclusively block cytokinesis without affecting progression through any other stage of the cell cycle. Thus, MiTMABs represent a new class of antimitotic compounds. We show that MiTMABs are potent inhibitors of cancer cell growth and have minimal effect on nontumorigenic fibroblast cells. Thus, MiTMABs have toxicity and antiproliferative properties that preferentially target cancer cells. This suggests that dynII may be a novel target for pharmacologic intervention for the treatment of cancer. PMID- 20571069 TI - MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. AB - The serine/threonine kinase Akt lies at a critical signaling node downstream of phosphatidylinositol-3-kinase and is important in promoting cell survival and inhibiting apoptosis. An Akt inhibitor may be particularly useful for cancers in which increased Akt signaling is associated with reduced sensitivity to cytotoxic agents or receptor tyrosine kinase inhibitors. We evaluated the effect of a novel allosteric Akt inhibitor, MK-2206, in combination with several anticancer agents. In vitro, MK-2206 synergistically inhibited cell proliferation of human cancer cell lines in combination with molecular targeted agents such as erlotinib (an epidermal growth factor receptor inhibitor) or lapatinib (a dual epidermal growth factor receptor/human epidermal growth factor receptor 2 inhibitor). Complementary inhibition of erlotinib-insensitive Akt phosphorylation by MK-2206 was one mechanism of synergism, and a synergistic effect was found even in erlotinib-insensitive cell lines. MK-2206 also showed synergistic responses in combination with cytotoxic agents such as topoisomerase inhibitors (doxorubicin, camptothecin), antimetabolites (gemcitabine, 5-fluorouracil), anti-microtubule agents (docetaxel), and DNA cross-linkers (carboplatin) in lung NCI-H460 or ovarian A2780 tumor cells. The synergy with docetaxel depended on the treatment sequence; a schedule of MK-2206 dosed before docetaxel was not effective. MK-2206 suppressed the Akt phosphorylation that is induced by carboplatin and gemcitabine. In vivo, MK-2206 in combination with these agents exerted significantly more potent tumor inhibitory activities than each agent in the monotherapy setting. These findings suggest that Akt inhibition may augment the efficacy of existing cancer therapeutics; thus, MK-2206 is a promising agent to treat cancer patients who receive these cytotoxic and/or molecular targeted agents. PMID- 20571070 TI - Variant isoforms of BCR-ABL1 in chronic myelogenous leukemia reflect alternative splicing of ABL1 in normal tissue - letter. PMID- 20571071 TI - Targeted therapies for non-small cell lung cancer: an evolving landscape. AB - Over the past decade, a multitude of targeted agents have been explored in the treatment of advanced non-small cell lung cancer (NSCLC). Thus far, two broad classes of agents have been implemented in clinical practice: (a) vascular endothelial growth factor (VEGF)-directed therapies and (b) antagonists of the epidermal growth factor receptor (EGFR). In the former category, the agent bevacizumab (a monoclonal antibody) has shown landmark improvements in survival when added to cytotoxic therapy. Small molecule tyrosine kinase inhibitors (TKI) targeting the VEGF receptor (i.e., sunitinib, sorafenib, and vandetanib) show activity in phase II clinical studies. With respect to EGFR-directed therapies, the TKIs gefitinib and erlotinib have shown significant benefit, and have uncovered valuable information about the biology of lung cancer. Outside of therapies directed specifically at VEGF- and EGFR-mediated signaling, trials evaluating insulin-like growth factor-1 receptor (IGF-IR)-targeting agents, cyclooxygenase-2 (COX-2) inhibitors, c-met inhibitors, irreversible pan-HER inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors are ongoing. Inhibitors of ALK show great promise in patients with the relevant gene translocation. Herein, the clinical development of novel therapies for NSCLC is described, including some discussion of relevant biomarkers and determination of synergy with both cytotoxic therapy and other targeted agents. PMID- 20571072 TI - Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy. AB - Melanoma responds poorly to standard chemotherapy due to its intrinsic chemoresistance. Multiple genetic and molecular defects, including an activating mutation in the BRaf kinase gene, are associated with melanoma, and the resulting alterations in signal transduction pathways regulating proliferation and apoptosis are thought to contribute to its chemoresistance. Sorafenib, a multikinase inhibitor that targets BRaf kinase, is Food and Drug Administration approved for use in advanced renal cell and hepatocellular carcinomas. Although sorafenib has shown little promise as a single agent in melanoma patients, recent clinical trials suggest that, when combined with chemotherapy, it may have more benefit. We evaluated the ability of sorafenib to augment the cytotoxic effects of melphalan, a regional chemotherapeutic agent, and temozolomide, used in systemic and regional treatment of melanoma, on a panel of 24 human melanoma derived cell lines and in an animal model of melanoma. Marked differences in response to 10 micromol/L sorafenib alone were observed in vitro across cell lines. Response to sorafenib significantly correlated with extracellular signal regulated kinase (ERK) downregulation and loss of Mcl-1 expression (P < 0.05). Experiments with the mitogen-activated protein kinase/ERK kinase inhibitor U0126 suggest a unique role for ERK downregulation in the observed effects. Sorafenib in combination with melphalan or temozolomide led to significantly improved responses in vitro (P < 0.05). In the animal model of melanoma, sorafenib in combination with regional melphalan or regional temozolomide was more effective than either treatment alone in slowing tumor growth. These results show that sorafenib in combination with chemotherapy provides a novel approach to enhance chemotherapeutic efficacy in the regional treatment of in-transit melanoma. PMID- 20571073 TI - A genetically encoded multifunctional TRAIL trimer facilitates cell-specific targeting and tumor cell killing. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L) has been shown to exhibit potent and specific apoptotic activity against tumor cells. Several TRAIL constructs have been tried in patients, and the molecule remains under active clinical investigation. Native and recombinant TRAIL must form a homotrimer to become biologically active. However, noncovalently associated TRAIL displays a high degree of sensitivity to degradation, which limits its therapeutic potential. To enforce trimerization of the recombinant protein, we developed a covalently linked TRAIL trimer (TR3) by genetic fusion. This molecular drug design conferred improved stability without altering the native killing ability of TRAIL. Target specificity was shown by blocking TR3 activity with soluble death receptor 5 (DR5-Fc). In addition, we have shown that TR3 is amenable to further, genetic modifications. The incorporation of additional functional domains to TR3, such as antibody fragments (scFvs) that allow for a more cell-specific delivery of the agent, is stoichiometrically controlled and inconsequential with regard to the bioactivity of TRAIL. As proof of this concept, TR3 activity was targeted to the mouse RBC membrane. TR3-decorated RBCs were effectively capable of target cell killing in a model of pancreatic cancer. TR3 represents a generally applicable platform tool to study basic mechanisms along the death receptor pathway. More importantly, the ability to target TR3 to a cell surface presents the opportunity to create a cancer-selective drug with fewer off-target toxicities and enhanced killing capacities. PMID- 20571074 TI - Mcl-1 stability determines mitotic cell fate of human multiple myeloma tumor cells treated with the kinesin spindle protein inhibitor ARRY-520. AB - Kinesin spindle protein (KSP/Eg5) inhibitors are novel anticancer agents that have thus far shown only modest activity in the clinic. Understanding how to identify patients who may be most sensitive to treatment is clearly needed to improve the development of these molecules. We studied four multiple myeloma cell lines treated with the KSP inhibitor ARRY-520 to identify factors important for initiating apoptosis while cells are arrested in mitosis. The majority (three of four) of cell lines underwent mitotic arrest, with apoptosis occurring in mitosis within 24 to 30 hours. The remaining line (NCI H929) is temporally refractory to ARRY-520 treatment, undergoing mitotic slippage and subsequently peaking in apoptotic markers after 72 hours of treatment, while most cells are in interphase. Interestingly, loss of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) coincided with mitotic cell death. Stabilization of Mcl-1 resulted in a delayed onset of apoptosis, whereas enforced downregulation of Mcl 1 increased cell death in response to KSP inhibition. Thus, variation in responses to KSP inhibition is governed by a balance between survival proteins and spindle checkpoint integrity. Cells relying on short-lived survival proteins during mitosis are more likely to undergo apoptosis in response to KSP inhibition. We propose that patients with hematologic malignancies, which rely on Mcl-1, would therefore be good candidates for treatment with KSP inhibitors. PMID- 20571075 TI - Sensitivity of cancer cells to Plk1 inhibitor GSK461364A is associated with loss of p53 function and chromosome instability. AB - Polo-like kinases are a family of serine threonine kinases that are critical regulators of cell cycle progression and DNA damage response. Predictive biomarkers for the Plk1-selective inhibitor GSK461364A were identified by comparing the genomics and genetics of a panel of human cancer cell lines with their response to a drug washout followed by an outgrowth assay. In this assay, cell lines that have lost p53 expression or carry mutations in the TP53 gene tended to be more sensitive to GSK461364A. These more sensitive cell lines also had increased levels of chromosome instability, a characteristic associated with loss of p53 function. Further mechanistic studies showed that p53 wild-type (WT) and not mutant cells can activate a postmitotic tetraploidy checkpoint and arrest at pseudo-G(1) state after GSK461364A treatment. RNA silencing of WT p53 increased the antiproliferative activity of GSK461364A. Furthermore, silencing of p53 or p21/CDKN1A weakened the tetraploidy checkpoint in cells that survived mitotic arrest and mitotic slippage. As many cancer therapies tend to be more effective in p53 WT patients, the higher sensitivity of p53-deficient tumors toward GSK461364A could potentially offer an opportunity to treat tumors that are refractory to other chemotherapies as well as early line therapy for these genotypes. PMID- 20571077 TI - Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. AB - Regulators of G protein signaling (RGS) proteins are potent negative modulators of G protein signaling and have been proposed as potential targets for small molecule inhibitor development. We report a high-throughput time-resolved fluorescence resonance energy transfer screen to identify inhibitors of RGS4 and describe the first reversible small-molecule inhibitors of an RGS protein. Two closely related compounds, typified by CCG-63802 [((2E)-2-(1,3-benzothiazol-2-yl) 3-[9-methyl-2-(3-methylphenoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl]prop-2 enenitrile)], inhibit the interaction between RGS4 and Galpha(o) with an IC(50) value in the low micromolar range. They show selectivity among RGS proteins with a potency order of RGS 4 > 19 = 16 > 8 >> 7. The compounds inhibit the GTPase accelerating protein activity of RGS4, and thermal stability studies demonstrate binding to the RGS but not to Galpha(o). On RGS4, they depend on an interaction with one or more cysteines in a pocket that has previously been identified as an allosteric site for RGS regulation by acidic phospholipids. Unlike previous small molecule RGS inhibitors identified to date, these compounds retain substantial activity under reducing conditions and are fully reversible on the 10-min time scale. CCG-63802 and related analogs represent a useful step toward the development of chemical tools for the study of RGS physiology. PMID- 20571076 TI - Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro. AB - This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 +/- 0.6 years) were cultured for 2-5 days. The turnover of 18 amino acids was measured in spent media by high-performance liquid chromatography. Embryos were either fixed for interphase fluorescent in situ hybridization analysis of chromosomes 13, 18, 19, 21, X or Y, or were assayed for mitochondrial activity. Amino acid turnover was different (P < 0.05) between stage-matched fresh and cryopreserved embryos due to blastomere loss following warming. The proportion of embryos with aneuploid cells increased as cell division progressed from pronucleate- (23%) to late cleavage stages (50-70%). Asparagine, glycine and valine turnover was significantly different between uniformly genetically normal and uniformly abnormal embryos on Days 2-3 of culture. By Days 3-4, the profiles of serine, leucine and lysine differed between uniformly euploid versus aneuploid embryos. Gender significantly (P < 0.05) affected the metabolism of tryptophan, leucine and asparagine by cleavage-stage embryos. Pronucleate zygotes had a significantly higher proportion of active:inactive mitochondria compared with cleavage-stage embryos. Furthermore, mitochondrial activity was correlated (P < 0.05) with altered aspartate and glutamine turnover. These results demonstrate the association between the metabolism, cytogenetic composition and health of human embryos in vitro. PMID- 20571078 TI - Regulation of mouse brain-selective sulfotransferase sult4a1 by cAMP response element-binding protein and activating transcription factor-2. AB - Sulfotransferase 4A1 (SULT4A1) is a novel cytosolic sulfotransferase that is primarily expressed in the brain. To date, no significant enzyme activity or biological function for the protein has been identified, although it is highly conserved between species. Mutations in the SULT4A1 gene have been linked to schizophrenia susceptibility, and recently, its stability was shown to be regulated by Pin1, a peptidyl-prolyl cis-trans isomerase implicated in several neurodegenerative diseases. In this study, we investigated the transcriptional regulation of mouse Sult4a1. Using a series of promoter deletion constructs, we identified three cAMP-responsive elements (CREs) that were required for maximal promoter activity. The CREs are located within 100 base pairs of the major transcription start site and are also present in the same region of the human SULT4A1 promoter. Electrophoretic mobility shift assays (EMSAs) identified two specific complexes that formed on each of the CREs. One complex contained cAMP response element-binding protein (CREB), and the other contained activating transcription factor-2 (ATF-2) and c-Jun. Overexpression of CREB or ATF-2 increased not only reporter promoter activity but also endogenous Sult4a1 mRNA levels in Neuro2a cells. Moreover, [d-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin (DAMGO) treatment increased both reporter promoter activity and Sult4a1 levels in mu-opioid receptor expressing Neuro2a/mu-opioid receptor cells, and EMSAs showed this to be due to increased binding of CREB and ATF-2 to the Sult4a1 promoter. We also show that DAMGO treatment increases Sult4a1 mRNA and protein levels in primary mouse neurons. These results suggest that Sult4a1 is a target gene for the mu-opioid receptor signaling pathway and other pathways involving activation of CREB and ATF-2. PMID- 20571079 TI - The effect of allosteric modulators on the kinetics of agonist-G protein-coupled receptor interactions in single living cells. AB - Allosteric binding sites on adenosine -A(1) and -A(3) receptors represent attractive therapeutic targets for amplifying, in a spatially and temporally selective manner, the tissue protective actions of endogenous adenosine. This study has directly quantified the kinetics of agonist/G protein-coupled receptor interactions at the single-cell level, reflecting the physiological situation in which intracellular signaling proteins can exert major allosteric effects on agonist-receptor interactions. The association and dissociation rate constants at both A(1) and A(3) receptors, and therefore the affinity of the fluorescent adenosine derivative ABA-X-BY630 (structure appears in J Med Chem 50:782-793, 2007), were concentration-independent. The equilibrium dissociation constants of ABA-X-BY630 at A(1) and A(3) receptors were approximately 50 and 10 nM, respectively, suggesting that, even in live cells, low agonist concentrations predominantly detect high-affinity receptor states. At A(1) receptors, the dissociation of ABA-X-BY630 (30 nM) was significantly faster in the absence (k(off) = 1.95 +/- 0.09 min(-1)) compared with the presence of the allosteric enhancer (2-amino-4,5-dimethyl-3-thienyl)(3-(trifluoromethyl)phenyl)-methanone (PD81,723; 10 microM; k(off) = 0.80 +/- 0.03 min(-1)) and allosteric inhibitor 4 methoxy-N-(7-methyl-3-(2-pyridinyl)-1-isoquinolinyl)benzamide (VUF5455; 1 microM; k(off) = 1.48 +/- 0.16 min(-1)). In contrast, ABA-X-BY630 dissociation from A(3) receptors was significantly slower in the absence (k(off) = 0.78 +/- 0.18 min( 1)) than in the presence of the allosteric inhibitors VUF5455 (1 microM; k(off) = 3.15 +/- 0.12 min(-1)) and PD81,723 (10 microM; k(off) = 2.46 +/- 0.18 min(-1)). An allosteric mechanism of action has previously not been identified for PD81,723 at the A(3) receptor or VUF5455 at the A(1) receptor. Furthermore, the marked enhancement in fluorescent agonist dissociation by VUF5455 in living cells contrasts previous observations from broken cell preparations and emphasizes the need to study the allosteric regulation of agonist binding in living cells. PMID- 20571080 TI - Single-stranded DNA binding protein from human malarial parasite Plasmodium falciparum is encoded in the nucleus and targeted to the apicoplast. AB - Apicoplast, an essential organelle of human malaria parasite Plasmodium falciparum contains a ~35 kb circular genome and is a possible target for therapy. Proteins required for the replication and maintenance of the apicoplast DNA are not clearly known. Here we report the presence of single-stranded DNA binding protein (SSB) in P falciparum. PfSSB is targeted to the apicoplast and it binds to apicoplast DNA. A strong ssDNA binding activity specific to SSB was also detected in P. falciparum lysate. Both the recombinant and endogenous proteins form tetramers and the homology modelling shows the presence of an oligosaccharide/oligonucleotide-binding fold responsible for ssDNA binding. Additionally, we used SSB as a tool to track the mechanism of delayed death phenomena shown by apicoplast targeted drugs ciprofloxacin and tetracycline. We find that the transport of PfSSB is severely affected during the second life cycle following drug treatment. Moreover, the translation of PfSSB protein and not the transcription of PfSSB seem to be down-regulated specifically during second life cycle although there is no considerable change in protein expression profile between drug-treated and untreated parasites. These results suggest dual control of translocation and translation of apicoplast targeted proteins behind the delayed death phenomena. PMID- 20571081 TI - BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression. AB - For DNA replication to occur, chromatin must be remodeled. Yet, we know very little about which proteins alter nucleosome occupancy at origins and replication forks and for what aspects of replication they are required. Here, we demonstrate that the BRG1 catalytic subunit of mammalian SWI/SNF-related complexes co localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers. The specific pattern of BRG1 occupancy suggests it does not participate in origin selection but is involved in the firing of origins and the process of replication elongation. This latter function is confirmed by the fact that Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation. This novel function of BRG1 is consistent with its requirement during embryogenesis and its role as a tumor suppressor to maintain genome stability and prevent cancer. PMID- 20571082 TI - Time-dependent increase in ribosome processivity. AB - We created a novel tripartite reporter RNA to separately and simultaneously examine ribosome translation rates at the 5'- and 3'-ends of a large open reading frame (ORF) in vitro in HeLa cell lysates. The construct contained Renilla luciferase (RLuc), beta-galactosidase and firefly luciferase (FLuc) ORFs linked in frame and separated by a viral peptide sequence that causes cotranslational scission of emerging peptide chains. The length of the ORF contributed to low ribosome processivity, a low number of initiating ribosomes completing translation of the entire ORF. We observed a time-dependent increase in FLuc production rate that was dependent on a poly(A) tail and poly(A)-binding protein, but was independent of eIF4F function. Stimulation of FLuc production occurred earlier on shorter RNA templates. Cleavage of eIF4G at times after ribosome loading on templates occurred did not cause immediate cessation of 5'-RLuc translation; rather, a delay was observed that shortened when shorter templates were translated. Electron microscopic analysis of polysome structures in translation lysates revealed a time-dependent increase in ribosome packing and contact that correlated with increased processivity on the FLuc ORF. The results suggest that ORF transit combined with PABP function contribute to interactions between ribosomes that increase or sustain processivity on long ORFs. PMID- 20571083 TI - A G-quadruplex structure within the 5'-UTR of TRF2 mRNA represses translation in human cells. AB - Telomeres protect chromosome ends from being recognized as double-stranded breaks. Telomeric function is ensured by the shelterin complex in which TRF2 protein is an essential player. The G-rich strand of telomere DNA can fold into G quadruplex (G4) structure. Small molecules stabilizing G4 structures, named G4 ligands, have been shown to alter telomeric functions in human cells. In this study, we show that a guanine-rich RNA sequence located in the 5'-UTR region of the TRF2 mRNA (hereafter 91TRF2G) is capable of forming a stable quadruplex that causes a 2.8-fold decrease in the translation of a reporter gene in human cells, as compared to a mutant 5'-UTR unable to fold into G4. We also demonstrate that several highly selective G4 ligands, the pyridine dicarboxamide derivative 360A and bisquinolinium compounds Phen-DC(3) and Phen-DC(6), are able to bind the 91TRF2G:RNA sequence and to modulate TRF2 protein translation in vitro. Since the naturally occurring 5'-UTR TRF2:RNA G4 element was used here, which is conserved in several vertebrate orthologs, the present data substantiate a potential translational mechanism mediated by a G4 RNA motif for the downregulation of TRF2 expression. PMID- 20571084 TI - Rational design of an orthogonal tryptophanyl nonsense suppressor tRNA. AB - While a number of aminoacyl tRNA synthetase (aaRS):tRNA pairs have been engineered to alter or expand the genetic code, only the Methanococcus jannaschii tyrosyl tRNA synthetase and tRNA have been used extensively in bacteria, limiting the types and numbers of unnatural amino acids that can be utilized at any one time to expand the genetic code. In order to expand the number and type of aaRS/tRNA pairs available for engineering bacterial genetic codes, we have developed an orthogonal tryptophanyl tRNA synthetase and tRNA pair, derived from Saccharomyces cerevisiae. In the process of developing an amber suppressor tRNA, we discovered that the Escherichia coli lysyl tRNA synthetase was responsible for misacylating the initial amber suppressor version of the yeast tryptophanyl tRNA. It was discovered that modification of the G:C content of the anticodon stem and therefore reducing the structural flexibility of this stem eliminated misacylation by the E. coli lysyl tRNA synthetase, and led to the development of a functional, orthogonal suppressor pair that should prove useful for the incorporation of bulky, unnatural amino acids into the genetic code. Our results provide insight into the role of tRNA flexibility in molecular recognition and the engineering and evolution of tRNA specificity. PMID- 20571085 TI - Identifying compositionally homogeneous and nonhomogeneous domains within the human genome using a novel segmentation algorithm. AB - It has been suggested that the mammalian genome is composed mainly of long compositionally homogeneous domains. Such domains are frequently identified using recursive segmentation algorithms based on the Jensen-Shannon divergence. However, a common difficulty with such methods is deciding when to halt the recursive partitioning and what criteria to use in deciding whether a detected boundary between two segments is real or not. We demonstrate that commonly used halting criteria are intrinsically biased, and propose IsoPlotter, a parameter free segmentation algorithm that overcomes such biases by using a simple dynamic halting criterion and tests the homogeneity of the inferred domains. IsoPlotter was compared with an alternative segmentation algorithm, D(JS), using two sets of simulated genomic sequences. Our results show that IsoPlotter was able to infer both long and short compositionally homogeneous domains with low GC content dispersion, whereas D(JS) failed to identify short compositionally homogeneous domains and sequences with low compositional dispersion. By segmenting the human genome with IsoPlotter, we found that one-third of the genome is composed of compositionally nonhomogeneous domains and the remaining is a mixture of many short compositionally homogeneous domains and relatively few long ones. PMID- 20571086 TI - A flexible and efficient template format for circular consensus sequencing and SNP detection. AB - A novel template design for single-molecule sequencing is introduced, a structure we refer to as a SMRTbell template. This structure consists of a double-stranded portion, containing the insert of interest, and a single-stranded hairpin loop on either end, which provides a site for primer binding. Structurally, this format resembles a linear double-stranded molecule, and yet it is topologically circular. When placed into a single-molecule sequencing reaction, the SMRTbell template format enables a consensus sequence to be obtained from multiple passes on a single molecule. Furthermore, this consensus sequence is obtained from both the sense and antisense strands of the insert region. In this article, we present a universal method for constructing these templates, as well as an application of their use. We demonstrate the generation of high-quality consensus accuracy from single molecules, as well as the use of SMRTbell templates in the identification of rare sequence variants. PMID- 20571087 TI - Predictive response-relevant clustering of expression data provides insights into disease processes. AB - This article describes and illustrates a novel method of microarray data analysis that couples model-based clustering and binary classification to form clusters of 'response-relevant' genes; that is, genes that are informative when discriminating between the different values of the response. Predictions are subsequently made using an appropriate statistical summary of each gene cluster, which we call the 'meta-covariate' representation of the cluster, in a probit regression model. We first illustrate this method by analysing a leukaemia expression dataset, before focusing closely on the meta-covariate analysis of a renal gene expression dataset in a rat model of salt-sensitive hypertension. We explore the biological insights provided by our analysis of these data. In particular, we identify a highly influential cluster of 13 genes--including three transcription factors (Arntl, Bhlhe41 and Npas2)-that is implicated as being protective against hypertension in response to increased dietary sodium. Functional and canonical pathway analysis of this cluster using Ingenuity Pathway Analysis implicated transcriptional activation and circadian rhythm signalling, respectively. Although we illustrate our method using only expression data, the method is applicable to any high-dimensional datasets. Expression data are available at ArrayExpress (accession number E-MEXP-2514) and code is available at http://www.dcs.gla.ac.uk/inference/metacovariateanalysis/. PMID- 20571088 TI - The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. AB - Mitotic chromosome segregation requires the removal of physical connections between sister chromatids. In addition to cohesin and topological entrapments, sister chromatid separation can be prevented by the presence of chromosome junctions or ongoing DNA replication. We will collectively refer to them as DNA mediated linkages. Although this type of structures has been documented in different DNA replication and repair mutants, there is no known essential mechanism ensuring their timely removal before mitosis. Here, we show that the dissolution of these connections is an active process that requires the Smc5/6 complex, together with Mms21, its associated SUMO-ligase. Failure to remove DNA mediated linkages causes gross chromosome missegregation in anaphase. Moreover, we show that Smc5/6 is capable to dissolve them in metaphase-arrested cells, thus restoring chromosome resolution and segregation. We propose that Smc5/6 has an essential role in the removal of DNA-mediated linkages to prevent chromosome missegregation and aneuploidy. PMID- 20571089 TI - DNA synapsis through transient tetramerization triggers cleavage by Ecl18kI restriction enzyme. AB - To cut DNA at their target sites, restriction enzymes assemble into different oligomeric structures. The Ecl18kI endonuclease in the crystal is arranged as a tetramer made of two dimers each bound to a DNA copy. However, free in solution Ecl18kI is a dimer. To find out whether the Ecl18kI dimer or tetramer represents the functionally important assembly, we generated mutants aimed at disrupting the putative dimer-dimer interface and analysed the functional properties of Ecl18kI and mutant variants. We show by atomic force microscopy that on two-site DNA, Ecl18kI loops out an intervening DNA fragment and forms a tetramer. Using the tethered particle motion technique, we demonstrate that in solution DNA looping is highly dynamic and involves a transient interaction between the two DNA-bound dimers. Furthermore, we show that Ecl18kI cleaves DNA in the synaptic complex much faster than when acting on a single recognition site. Contrary to Ecl18kI, the tetramerization interface mutant R174A binds DNA as a dimer, shows no DNA looping and is virtually inactive. We conclude that Ecl18kI follows the association model for the synaptic complex assembly in which it binds to the target site as a dimer and then associates into a transient tetrameric form to accomplish the cleavage reaction. PMID- 20571090 TI - 5'-UTR G-quadruplex structures acting as translational repressors. AB - Given that greater than 90% of the human genome is expressed, it is logical to assume that post-transcriptional regulatory mechanisms must be the primary means of controlling the flow of information from mRNA to protein. This report describes a robust approach that includes in silico, in vitro and in cellulo experiments permitting an in-depth evaluation of the impact of G-quadruplexes as translational repressors. Sequences including potential G-quadruplexes were selected within nine distinct genes encoding proteins involved in various biological processes. Their abilities to fold into G-quadruplex structures in vitro were evaluated using circular dichroism, thermal denaturation and the novel use of in-line probing. Six sequences were observed to fold into G-quadruplex structures in vitro, all of which exhibited translational inhibition in cellulo when linked to a reporter gene. Sequence analysis, direct mutagenesis and subsequent experiments were performed in order to define the rules governing the folding of G-quadruplexes. In addition, the impact of single-nucleotide polymorphism was shown to be important in the formation of G-quadruplexes located within the 5'-untranslated region of an mRNA. In light of these results, clearly the 5'-UTR G-quadruplexes represent a class of translational repressors that is broadly distributed in the cell. PMID- 20571091 TI - Coronary slow flow: a potential prognostic marker correlating with the disease severity in renal failure? PMID- 20571092 TI - SIRTing out the link between autophagy and ageing. PMID- 20571093 TI - Gitelman syndrome in Gypsy paediatric patients carrying the same intron 9 + 1 G>T mutation. Clinical features and impact on quality of life. AB - BACKGROUND: Gitelman syndrome is a primary tubular disorder causing hypokalaemic metabolic alkalosis with hypocalciuria. Its prevalence is high in Gypsies, who harbour an identical mutation, intron 9 + 1 G>T, in the SLC12A3 gene. METHODS: To better define the Gitelman syndrome in Gypsies, the clinical and biochemical features of 34 Spanish paediatric Gypsy patients were analysed. At diagnosis, symptoms, height and weight as well as serum and urinary biochemical data were collected. During a follow-up of 4.5 +/- 2.4 years [X +/- standard deviation (SD)], therapy, treatment compliance, symptoms, frequency of hospital admissions and, at the last visit, growth and biochemical work-up of 29 patients followed for at least 6 months were analysed. Quality of life items were also assessed by a questionnaire. RESULTS: Muscle cramps (41%) and asthenia (35%) were the most frequent presenting symptoms. Biochemical data at diagnosis were serum K 2.76 +/- 0.46 mEq/L, serum Mg 1.32 +/- 0.28 mg/dL, blood pH 7.45 +/- 0.06, serum bicarbonate 28.2 +/- 2.9 mEq/L, urinary calcium/creatinine ratio 0.03 +/- 0.04 mg/mg, fractional K excretion 24.4 +/- 17.1% and fractional Mg excretion 8.9 +/- 8.3%. During follow-up, Mg and K supplements were prescribed to 79 and 86% of patients, respectively; compliance with treatment was good in 35%. Hospital admission rate was 0.03/patient/month. Muscle cramps were the symptom most often referred by the patients (45%) during the follow-up, and 71% of patients considered their health status as excellent or good. Twenty-one patients stated that their disease did not adversely interfere with their mood or social relationships. Height and weight of patients at diagnosis were -0.60 +/- 1.17 and -0.49 +/- 1.32 SD, respectively, and improved to -0.44 +/- 1.28 (P < 0.05) and 0.18 +/- 1.79 SD (P < 0.01) at the last visit. CONCLUSIONS: Gypsy children with Gitelman syndrome mostly exhibit muscle symptoms and asthenia although the disease is not particularly severe in this ethnic group. Body growth improves with treatment and close follow-up. PMID- 20571094 TI - Vegetarian supplemented low-protein diets. A safe option for pregnant CKD patients: report of 12 pregnancies in 11 patients. AB - BACKGROUND: Pregnancy in CKD is an increasing challenge, considering also the paucity of therapeutic tools available in pregnant women. While theoretically interesting, the experience with low protein diets in pregnancy is limited. Aim of this feasibility study is to review our experience with supplemented vegetarian low protein diets in pregnancy, as a "rescue treatment" for severe CKD and/or proteinuria. METHODS: Data were gathered prospectively. Diet schema: proteins: 0.6-0.7 g/Kg/day, amino and chetoacid supplementation, 1-3 free meals/week. Compliance, side effects, biochemical data recorded at each visit (at least twice monthly). RESULTS: Between January 2000 and February 2010, out of 168 pregnancies referred, 12 were managed by the diet (11 patients; median age 33, range 20-38). One pregnancy was terminated (patient's choice); the other 10 patients delivered 11 healthy babies. At referral, 2 patients were in stage 4 CKD, 4 in stage 3, 4 had nephrotic proteinuria (3.6-6.3 g/day). One patient doubled serum creatinine; none needed renal replacement therapy within 6 months from delivery. No patient complained of side effects, nor developed hyperkalemia or hypercalcaemia. Two babies from mothers in CKD stage 4 were small for gestational age; 9/11 were delivered by caesarean section (median gestational age 33 weeks: range 28-37; birth weight 935-2620 g) within a policy of delivery in the presence of foetal growth impairment and/or worsening of proteinuria, GFR, hypertension or foetal conditions. All babies are well, 1 month, 7.5 years from delivery. CONCLUSION: Our report suggests considering vegetarian diets as an additional tool in the management of pregnant CKD patients. PMID- 20571095 TI - Proteomic biomarkers in diabetic nephropathy--reality or future promise? PMID- 20571096 TI - Haemodynamic stability in standard bicarbonate haemodialysis and long-hour slow flow bicarbonate haemodialysis. AB - BACKGROUND: The interplay of correct solute mass balances, such as that of sodium (Na+) and potassium (K+) (respectively, Na+MB and K+MB) with adequate ultrafiltration volumes (V(UF)), is crucial in order to achieve haemodynamic stability during haemodialysis (HD). The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the unique opportunity of effecting mass balances of any solute in a very precise way. METHODS: The present study has a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions, one of 4 h and the other of 8 h in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialysers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, V(UF) and dialysate Na+ and K+ concentrations were prescribed to be the same. Plasma water Na+ and K+ trends during dialysis as well as Na+MBs and K+MBs were determined. At the same time, systolic blood pressure (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate trends during dialysis were analysed. Plasma volume (PV) changes were computed from plasma total protein concentrations and their trends analysed. RESULTS: Plasma water Na+ and K+ levels were not significantly different when comparing the start and the end of the sessions of the two treatments. Both the increase of plasma water Na+ levels and the decrease of plasma water K+ levels in the first 4 h were significantly slower during the 8 h sessions when compared with the 4-h ones (P < 0.048 and P < 0.006, respectively). Dialysis sessions were uneventful. SBP decreased significantly during the 4-h sessions, whereas it remained stable during the 8-h ones (P < 0.0001 and P = NS, respectively). Statistically significantly lower intradialysis decreases of SBP (-4.5 +/- 16.2 vs -20.0 +/- 15.0 mmHg, P < 0.02) and MAP (-1.4 +/- 11.7 vs -8.6 +/- 11.0 mmHg, P < 0.04) were achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no significant difference for mean V(UF) (2.9 +/- 0.9 vs 2.9 +/- 0.8 L; P = NS) and mean Na+MBs (-298.1 +/- 142.2 vs 286.2 +/- 150.7 mmol; P = NS). The decrease of PV levels in the first 4 h was significantly slower during the 8-h sessions when compared with the 4-h ones (P < 0.0001). PV decrease was significantly higher at the end of the 4-h HD sessions than at the end of the 8-h HD sessions (P < 0.043). CONCLUSIONS: The present highly controlled experiments using a crossover design and precise Na+MB and K+MB controls showed that better haemodynamic stability was achieved in the 8-h sessions with respect to the 4-h sessions, in spite of no difference for mean V(UF) and Na+MBs. Thus, other pathophysiological mechanisms, namely, a better PV preservation, must be advocated in order to explain the better haemodynamic stability peculiar to long-hour slow-flow nocturnal HD treatments. PMID- 20571097 TI - Low-GDP peritoneal dialysis fluid ('balance') has less impact in vitro and ex vivo on epithelial-to-mesenchymal transition (EMT) of mesothelial cells than a standard fluid. AB - BACKGROUND: Peritoneal membrane deterioration during peritoneal dialysis (PD) is associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MC), which is believed to be mainly due to glucose degradation products (GDPs) present in PD solutions. Here we investigate the impact of GDPs in PD solutions on the EMT of MC in vitro and ex vivo. METHODS: For in vitro studies, omentum derived MC were incubated with standard PD fluid or low-GDP solution diluted 1:1 with culture medium. For ex vivo studies, 33 patients, who were distributed at random to either the 'standard' or the 'low GDP' groups, were followed over 24 months. Effluents were collected every 6 months to determine EMT markers in effluent MC. RESULTS: Exposure of MC to standard fluid in vitro resulted in morphological change into a non-epitheloid shape, down-regulation of E-cadherin, indicative of EMT, and in a strong induction of vascular endothelial growth factor (VEGF) expression. In contrast, in vitro exposure of MC to low-GDP solution did not lead to these phenotype changes. This could be confirmed ex vivo, as the prevalence of non-epitheloid phenotype of MC in the standard group was significantly higher with increasing PD duration and MC isolated from this group showed significantly higher levels of EMT-associated molecules including fibronectin, collagen I, VEGF, IL-8 and TGF-beta levels when compared with the low-GDP group. Over time, the expression of E-cadherin also decreased in the standard but increased in the low-GDP group. In addition, the levels of EMT associated molecules (fibronectin, VEGF and IL-8) increased in the standard but decreased in the low-GDP group. A similar trend was also observed for collagen I and for TGF-beta (for the first year), but did not reach global statistical significance. Accordingly, effluent MC with non-epitheloid morphology showed significantly lower levels of E-cadherin and greater levels of fibronectin, collagen I, VEGF and IL 8 when compared with MC with epitheloid phenotype. The incidence of peritonitis did not significantly influence these results. Drop-out due to technique failure was less in the 'balance' group. The functional, renal and peritoneal evaluation of patients being treated with either standard or 'balance' fluid did not show any significant difference over time. CONCLUSIONS: MC from PD effluent of patients treated with a PD fluid containing low GDP levels show fewer signs of EMT and the respective molecules than MC from patients treated with standard fluid, indicating a better preservation of the peritoneal membrane structure and a favourable outcome in patients using low-GDP fluid. It also confirms the hypothesis that the protection of EMT by GDP-reduced fluids is also present in vivo. PMID- 20571098 TI - Increasing size of health centres may not prevent occupational isolation. AB - BACKGROUND: A Finnish national survey in 2002 revealed that Finnish physicians often feel that working in a primary heath care centre is isolated work. AIMS: To determine the factors related to perceived isolation in health centre work among general practitioners (GP) working in health centres. METHODS: A postal questionnaire study of physicians (N = 1829) working in primary health care centres. RESULTS: The majority of GPs (67%) agreed that 'working in a health centre is too often isolated work'. Physicians felt isolated most often when working in the largest health centres (>20 posts), whereas physicians working in health centres with 3-10 posts perceived isolation least often. Difficulty in collaboration with partners or the managerial team was associated with this feeling. CONCLUSIONS: Feelings of isolation are common among Finnish health centre physicians, but increasing the size of primary health care units may not prevent these feelings. PMID- 20571099 TI - Occupational isolation among general practitioners in Finland. AB - BACKGROUND: It is proposed that isolation in general practice is one of the factors that leads to work-related stress and the low attraction of this work. In Finland, 71% of physicians who worked or had worked in a primary health care centre agreed with the statement 'working as a doctor in a health centre is too often isolated work'. AIMS: To gain a deeper understanding of this feeling and to find out which factors constitute it. METHODS: A qualitative in-depth interview study of 32 physicians working in a primary health care centre in Finland. Qualitative analysis of transcribed verbatim interviews using a constant comparison method. RESULTS: The main components of isolation were making decisions alone, lack of collaboration with other workers in the health centre and secondary care specialists, not being a part of the work community and lack of mentoring at work. CONCLUSIONS: Enabling flexible teamwork and social and professional support networks are the key issues in solving the problem of occupational isolation in general practice. PMID- 20571100 TI - Impact of supervisor support on work ability in an IT company. AB - BACKGROUND: Work ability is the ability of a worker to perform his job. The authors hypothesized that supervisor support influences the work ability of workers working in an information technology company located in Tokyo. AIMS: To assess whether or not support from supervisors influences work ability. METHODS: Two surveys using the Brief Job Scale Questionnaire and the Work Ability Index (WAI) were conducted, one in October 2007 and the other in October 2008 on the same cohort. Two cross-sectional analyses and a 1-year longitudinal analysis were conducted using multiple regression analysis. In addition, the relationships between supervisor support and each dimension of WAI were analysed separately. RESULTS: The number of participants was 1157 males. Significant relationships were observed between supervisor support and WAI scores in both survey periods after adjusting for age, job demand, job control, work group size, job rank and job type. The 2007 Supervisor support was a significant predictor of 2008 WAI that raised the possibility that supervisor support does influence WAI scores. From the analysis of each dimension of WAI, a strong relationship between supervisor support and WAI was observed for the sections of the WAI that assessed work capacity but not for the sections that assessed the personal health status of respondents. CONCLUSIONS: Supervisor support is an important predictor of work ability. Supervisor support is associated with the questions of the WAI that assess not only work demands but also person's resources of the work ability model. PMID- 20571101 TI - Intern pharmacists as change agents to improve the practice of nonprescription medication supply: provision of salbutamol to patients with asthma. AB - BACKGROUND: Earlier work established an evidence practice gap during provision of nonprescription salbutamol (albuterol). Pharmacist interns are hypothesized to be in a position to improve professional practice in the community pharmacy setting. OBJECTIVE: To explore the potential of intern pharmacists to improve the professional practice of community pharmacy staff in the provision of nonprescription salbutamol. METHODS: Intern pharmacists (n = 157) delivered an asthma intervention in 136 pharmacies consisting of an educational activity to pharmacy staff and a health promotion campaign to consumers. Post-intervention, simulated patients presented to 100 intervention and 100 control community pharmacies with a request for salbutamol. The appropriate outcome was medical referral for poor asthma control and correction of poor inhaler technique. Incidence and quantity of patient assessment and counseling provided during the visit were also assessed. Logistic regression was used to determine the predictors of medical referral. RESULTS: A doubling in the rate of medical referral was seen in the intervention group (19% vs 40%; p = 0.001). Assessment of reliever use frequency was the main predictor of medical referral (OR = 22.7; 95% CI 9.06 to 56.9). Correction of poor inhaler technique did not improve; however, a reduction in salbutamol supplied without patient assessment (23% vs 8%; p = 0.009) or counseling (75% vs 48%; p < 0.001) was noted. CONCLUSIONS: A doubling in the rate of medical referral showed a clear improvement in professional practice during the provision of nonprescription salbutamol. The improved patient outcome in the intervention group was due to increased assessment of reliever use frequency. Identification of poor inhaler technique remained near zero in both groups, which suggests that intern pharmacists were able to improve the current practice of community pharmacies yet were unable to establish a new practice behavior. This study provides evidence that intern pharmacists can act as change agents to improve pharmacy practice. PMID- 20571102 TI - Performance of community pharmacists in providing clinical medication reviews. AB - BACKGROUND: Drug-related problems (DRPs) may result in adverse drug reactions causing hospital admissions (5-17%); older patients in particular may experience such reactions during a hospital stay (6-17%). While community pharmacists can identify DRPs through clinical medication reviews, little is known about how well they perform in providing such reviews. OBJECTIVE: To assess trained community pharmacists' performance in writing care plans and referrals when providing clinical medication reviews to elderly patients as part of a patient outcome focused Medicines Management project. METHODS: In the south of England, 43 community pharmacists were recruited from 80 local community pharmacies; 37 completed clinical pharmacy training to provide medication reviews for elderly patients who were receiving prescriptions for 4 or more medicines from local general practices. Eleven trained pharmacists withdrew and did not provide any reviews. As part of quality assurance, a clinical pharmacist reviewed all care plans and referrals written by the community pharmacists and, if required, amended referrals before they were sent to the patients' family physicians with recommendations. The referrals written by the community pharmacists were compared with those written by the clinical pharmacist and were deemed to be accurate or incomplete (the community pharmacists could provide verbal information to the physicians) if the observations of DRPs and suggestions to solve them were beneficial to patients. Incorrect or missing observations and suggestions were considered nonbeneficial to patients. RESULTS: The performance assessment was based on a sample of 244 referrals written by 20 community pharmacists. The clinical pharmacist identified 908 DRPs and suggested 1489 solutions; the community pharmacists beneficially identified 75% of these DRPs (1% were incorrectly identified and 24% were missed) and suggested 58% of the solutions (6% were incorrectly suggested and 36% were missed). CONCLUSIONS: The community pharmacists beneficially identified most DRPs and suggested many solutions. However, the assessment may underestimate the community pharmacists' abilities, as it relied on the records they kept and was based on a gold standard. While the pharmacists were self-selected, this study provides valuable insight into trained community pharmacists' clinical medication review performance. PMID- 20571103 TI - Piperacillin/tazobactam--induced petechial rash. PMID- 20571104 TI - Fulminant hepatitis possibly related to pizotifen therapy. PMID- 20571105 TI - Assessing anticoagulation knowledge in patients new to warfarin therapy. AB - BACKGROUND: Warfarin is highly efficacious for the treatment and prevention of thromboembolic disorders. However, anticoagulation control has been a long standing challenge, as patients' lack of knowledge of warfarin therapy is a predictor of nonadherence and compromised patient safety. OBJECTIVE: To ascertain whether hospitalized patients newly initiated on warfarin are provided adequate anticoagulation education during hospitalization, as measured at discharge, as well as determine whether there is a difference in the knowledge obtained by patients educated via a structured program versus those counseled by "usual care." METHODS: A prospective evaluation of warfarin education of inpatients new to warfarin therapy was performed at Bassett Medical Center, Cooperstown, NY. Patients who were admitted to the hospital and receiving warfarin for any given diagnosis, were >18 years of age and able to give informed consent, and spoke English were recruited. Patients with dementia or cognitive impairment, those who were pregnant, or those who had previously been on warfarin therapy were excluded. Recruited patients received warfarin education in the form of a structured program provided by a pharmacist or counseling by usual care during hospitalization. Prior to discharge, the Oral Anticoagulation Knowledge (OAK) test, a prevalidated tool used to measure warfarin knowledge, was administered to evaluate outcomes. Further warfarin education was provided posttest if necessary. RESULTS: The intervention group (n = 20) scored significantly higher on the OAK test than the usual care group (n = 20): 74% versus 55%, respectively (p = 0.004). CONCLUSIONS: This preliminary study demonstrated that there is a large amount of variability regarding patient knowledge of warfarin on discharge from an inpatient facility. A formalized inpatient warfarin education program may empower patients to achieve a larger degree of initial warfarin knowledge than those educated by usual care. Previous studies have demonstrated that this may improve adherence and subsequently increase long-term safety associated with oral anticoagulation. Larger, prospective, randomized studies are necessary to further evaluate patient education and safety outcomes. PMID- 20571106 TI - Hyperglycemia management using insulin in the acute care setting: therapies and strategies for care in the non-critically ill patient. AB - BACKGROUND: Hyperglycemia is prevalent in hospitalized non-critically ill patients and is associated with higher morbidity and mortality. Poor glycemic control is related to elevated costs due to longer hospital stays and higher rates of complications. OBJECTIVE: To review current literature evaluating treatment strategies for management of hyperglycemia in the non-critically ill hospitalized patient and to discuss the role of pharmacists in glycemia management. DATA SOURCES: A literature review (January 2000-January 2010) was conducted via PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined Health Information Database, and Education Resources Information Center. MeSH terms for diabetes were used along with stress hyperglycemia, insulin therapy, and insulin analogs in combination with non critically ill, hospitalized, acute care, or inpatient. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were reviewed for inclusion. Clinical trial reports, practice guidelines, and reviews involving insulin therapies and/or quality improvement initiatives for hyperglycemia in the acute care setting were evaluated. A total of 133 citations were reviewed and an additional 11 citations were identified from reference lists. DATA SYNTHESIS: The association between hyperglycemia and increased mortality is recognized in the acute care setting among critically ill patients; however, data to support glycemia management in non-critically ill patients continue to be established. National consensus guidelines support strategies for glycemia control that focus on insulin therapy and treatment-driven protocols. These initiatives can result in quality improvement when led by multidisciplinary teams, including pharmacists. Literature supports a pharmacist role in glucose monitoring and insulin dosing. CONCLUSIONS: Management of hyperglycemia is a critical component of acute care. Insulin treatment regimens and protocols for non-critically ill patients in the acute care setting are evolving with recognition of ideal glucose targets to prevent adverse outcomes. Glycemia management can be complex and presents opportunities for pharmacist involvement. PMID- 20571107 TI - Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required. AB - In the present study, the zebrafish breakdance mutant (bre) was used to assess the role of blood flow in development because it has been previously shown that bre larvae have a chronically reduced cardiac output as a result of ventricular contraction following only every second atrial contraction in addition to an atrial bradycardia. We confirmed a 50% reduction compared with control fish and further showed that blood flow in the caudal part of the dorsal aorta decreased by 80%. Associated with these reductions in blood flow were indications of developmental retardation in bre mutants, specifically delayed hatching, reduced cell proliferation, and a transiently decreased growth rate. Surprisingly, an increased red blood cell concentration and an earlier appearance of trunk vessels in bre larvae indicated some compensation to convective oxygen transport, although in previous studies it has been shown that zebrafish larvae at this stage obtain oxygen by bulk diffusion. In bre animals immunohistochemical analyses showed a significant increase in hypoxia inducible factor 1 (HIF)-alpha protein expression, comparable with wild-type larvae that were raised under hypoxic conditions. Accordingly, the expression of some hif downstream genes was affected. Furthermore, Affymetrix microarray analyses revealed a large number of genes that were differently expressed comparing control and bre larvae, and the number even increased with proceeding development. The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae. PMID- 20571108 TI - Confirmation of multiple seizure susceptibility QTLs on chromosome 15 in C57BL/6J and DBA/2J inbred mice. AB - To confirm seizure susceptibility (SZS) quantitative trait loci (QTLs) on chromosome (chr) 15 identified previously using C57BL/6J (B6) and DBA/2J (D2) mice and to refine their genomic map position, we studied a set of three congenic strains in which overlapping segments of chr 15 from D2 were transferred onto the B6 background. We measured thresholds for generalized electroshock seizure (GEST) and maximal electroshock seizure (MEST) in congenic strains and B6-like littermates and also tested their responses to kainic acid (KA) and pentylenetetrazol (PTZ). Results document that MEST is significantly lower in strains 15M and 15D, which harbor medial and distal (telomeric) segments of chr 15 (respectively) from D2, compared with strain 15P, which harbors the proximal (acromeric) segment of chr 15 from D2, and with control littermates. Congenic strains 15P and 15M exhibited greater KA SZS compared with strain 15D and B6-like controls. All congenic strains were similar to controls with regard to PTZ SZS. Taken together, results suggest there are multiple SZS QTLs on chr 15 and that two QTLs harbor gene variants that affect MEST and KA SZS independently. The MEST QTL is refined to a 19 Mb region flanked by rs13482630 and D15Mit159. This interval contains 350 genes, 183 of which reside in areas where the polymorphism rate between B6 and D2 is high. The KA QTL interval spans a 65 Mb region flanked by markers D15Mit13 and rs31271969. It harbors 83 genes in highly polymorphic areas, 310 genes in all. Complete dissection of these loci will lead to identification of genetic variants that influence SZS in mice and provide a better understanding of seizure biology. PMID- 20571111 TI - Transcriptome profiling in response to adiponectin in human cancer-derived cells. AB - The adipocyte-derived hormone adiponectin exerts protective actions in several disorders, including some cancers. However, while growing data suggest that adiponectin could be an effective anticancer agent, its mechanism of action in cancer cells is still poorly known. Here, using microarrays, we identified a set of 1,301 genes commonly modulated in three cancer-derived cell lines in response to short-term stimulation with full-length recombinant human adiponectin. Most of these genes are involved in translation regulation, immune or stress responses, and cell proliferation. Furthermore, among genes linked to disease that were retrieved by functional enrichment tests using text mining based on PubMed analysis, we found that 66% are involved in malignant neoplasms, further supporting the link between adiponectin and cancer mechanisms. Bioinformatic analysis demonstrated the diversity of signaling pathways and transcription factors potentially mediating adiponectin effects on gene expression, illustrating the complexity of adiponectin mechanisms of action in cancer cells. PMID- 20571109 TI - Naturally occurring mutations in the canine CFTR gene. AB - Naturally occurring cystic fibrosis (CF)-causing mutations in the CFTR gene have not been identified in any nonhuman animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans (e.g., bronchiectasis and pancreatitis), we hypothesized that dogs with these disorders likely have a higher expression rate of CFTR mutations than the at-large population. Temporal temperature-gradient gel electrophoresis (TTGE) was used to screen canine CFTR in 400 animals: 203 dogs diagnosed with pancreatitis, 23 dogs diagnosed with bronchiectasis, and 174 dogs admitted to clinics for any illness (at-large dogs). Twenty-eight dogs were identified with one of four CFTR missense mutations. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has approximately 20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W disrupts a highly conserved protein kinase A recognition site within the regulatory domain. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. No substantive differences in mutation frequency were observed between the at-large, pancreatitis, and bronchiectasis dogs. PMID- 20571112 TI - A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis mitogen activated protein kinase kinases. AB - The successful recognition of pathogen-associated molecular patterns (PAMPs) as a danger signal is crucial for plants to fend off numerous potential pathogenic microbes. The signal is relayed through mitogen-activated protein kinase (MPK) cascades to activate defenses. Here, we show that the Pseudomonas syringae type III effector HopF2 can interact with Arabidopsis thaliana MAP KINASE KINASE5 (MKK5) and likely other MKKs to inhibit MPKs and PAMP-triggered immunity. Inhibition of PAMP-induced MPK phosphorylation was observed when HopF2 was delivered naturally by the bacterial type III secretion system. In addition, HopF2 Arg-71 and Asp-175 residues that are required for the interaction with MKK5 are also necessary for blocking MAP kinase activation, PAMP-triggered defenses, and virulence function in plants. HopF2 can inactivate MKK5 and ADP-ribosylate the C terminus of MKK5 in vitro. Arg-313 of MKK5 is required for ADP-ribosylation by HopF2 and MKK5 function in the plant cell. Together, these results indicate that MKKs are important targets of HopF2. PMID- 20571115 TI - Regulation of freezing tolerance and flowering in temperate cereals: the VRN-1 connection. AB - In winter wheat (Triticum spp.) and barley (Hordeum vulgare) varieties, long exposures to nonfreezing cold temperatures accelerate flowering time (vernalization) and improve freezing tolerance (cold acclimation). However, when plants initiate their reproductive development, freezing tolerance decreases, suggesting a connection between the two processes. To better understand this connection, we used two diploid wheat (Triticum monococcum) mutants, maintained vegetative phase (mvp), that carry deletions encompassing VRN-1, the major vernalization gene in temperate cereals. Homozygous mvp/mvp plants never flower, whereas plants carrying at least one functional VRN-1 copy (Mvp/-) exhibit normal flowering and high transcript levels of VRN-1 under long days. The Mvp/- plants showed reduced freezing tolerance and reduced transcript levels of several cold induced C-REPEAT BINDING FACTOR transcription factors and COLD REGULATED genes (COR) relative to the mvp/mvp plants. Diploid wheat accessions with mutations in the VRN-1 promoter, resulting in high transcript levels under both long and short days, showed a significant down-regulation of COR14b under long days but not under short days. Taken together, these studies suggest that VRN-1 is required for the initiation of the regulatory cascade that down-regulates the cold acclimation pathway but that additional genes regulated by long days are required for the down-regulation of the COR genes. In addition, our results show that allelic variation in VRN-1 is sufficient to determine differences in freezing tolerance, suggesting that quantitative trait loci for freezing tolerance previously mapped on this chromosome region are likely a pleiotropic effect of VRN-1 rather than the effect of a separate closely linked locus (FROST RESISTANCE 1), as proposed in early freezing tolerance studies. PMID- 20571118 TI - Mushrooms: morphological complexity in the fungi. PMID- 20571120 TI - Reverse engineering dynamic temporal models of biological processes and their relationships. AB - Biological processes such as circadian rhythms, cell division, metabolism, and development occur as ordered sequences of events. The synchronization of these coordinated events is essential for proper cell function, and hence the determination of critical time points in biological processes is an important component of all biological investigations. In particular, such critical time points establish logical ordering constraints on subprocesses, impose prerequisites on temporal regulation and spatial compartmentalization, and situate dynamic reorganization of functional elements in preparation for subsequent stages. Thus, building temporal phenomenological representations of biological processes from genome-wide datasets is relevant in formulating biological hypotheses on: how processes are mechanistically regulated; how the regulations vary on an evolutionary scale, and how their inadvertent disregulation leads to a diseased state or fatality. This paper presents a general framework (GOALIE) to reconstruct temporal models of cellular processes from time-course gene expression data. We mathematically formulate the problem as one of optimally segmenting datasets into a succession of "informative" windows such that time points within a window expose concerted clusters of gene action whereas time points straddling window boundaries constitute points of significant restructuring. We illustrate here how GOALIE successfully brings out the interplay between multiple yeast processes, inferred from combined experimental datasets for the cell cycle and the metabolic cycle. PMID- 20571116 TI - Composition, variability, and temporal stability of the intestinal microbiota of the elderly. AB - Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability. PMID- 20571113 TI - An orange ripening mutant links plastid NAD(P)H dehydrogenase complex activity to central and specialized metabolism during tomato fruit maturation. AB - In higher plants, the plastidial NADH dehydrogenase (Ndh) complex supports nonphotochemical electron fluxes from stromal electron donors to plastoquinones. Ndh functions in chloroplasts are not clearly established; however, its activity was linked to the prevention of the overreduction of stroma, especially under stress conditions. Here, we show by the characterization of Orr(Ds), a dominant transposon-tagged tomato (Solanum lycopersicum) mutant deficient in the NDH-M subunit, that this complex is also essential for the fruit ripening process. Alteration to the NDH complex in fruit changed the climacteric, ripening associated metabolites and transcripts as well as fruit shelf life. Metabolic processes in chromoplasts of ripening tomato fruit were affected in Orr(Ds), as mutant fruit were yellow-orange and accumulated substantially less total carotenoids, mainly beta-carotene and lutein. The changes in carotenoids were largely influenced by environmental conditions and accompanied by modifications in levels of other fruit antioxidants, namely, flavonoids and tocopherols. In contrast with the pigmentation phenotype in mature mutant fruit, Orr(Ds) leaves and green fruits did not display a visible phenotype but exhibited reduced Ndh complex quantity and activity. This study therefore paves the way for further studies on the role of electron transport and redox reactions in the regulation of fruit ripening and its associated metabolism. PMID- 20571114 TI - Three Arabidopsis fatty acyl-coenzyme A reductases, FAR1, FAR4, and FAR5, generate primary fatty alcohols associated with suberin deposition. AB - Suberin is a protective hydrophobic barrier consisting of phenolics, glycerol, and a variety of fatty acid derivatives, including C18:0-C22:0 primary fatty alcohols. An eight-member gene family encoding alcohol-forming fatty acyl coenzyme A reductases (FARs) has been identified in Arabidopsis (Arabidopsis thaliana). Promoter-driven expression of the beta-glucuronidase reporter gene indicated that three of these genes, FAR1(At5g22500), FAR4(At3g44540), and FAR5(At3g44550), are expressed in root endodermal cells. The three genes were transcriptionally induced by wounding and salt stress. These patterns of gene expression coincide with known sites of suberin deposition. We then characterized a set of mutants with T-DNA insertions in FAR1, FAR4, or FAR5 and found that the suberin compositions of roots and seed coats were modified in each far mutant. Specifically, C18:0-OH was reduced in far5-1, C20:0-OH was reduced in far4-1, and C22:0-OH was reduced in far1-1. We also analyzed the composition of polymer-bound lipids of leaves before and after wounding and found that the basal levels of C18:0-C22:0 primary alcohols in wild-type leaves were increased by wounding. In contrast, C18:0-OH and C22:0-OH were not increased by wounding in far5-1 and far1 1 mutants, respectively. Heterologous expression of FAR1, FAR4, and FAR5 in yeast confirmed that they are indeed active alcohol-forming FARs with distinct, but overlapping, chain length specificities ranging from C18:0 to C24:0. Altogether, these results indicate that Arabidopsis FAR1, FAR4, and FAR5 generate the fatty alcohols found in root, seed coat, and wound-induced leaf tissue. PMID- 20571110 TI - In silico structure-function analysis of pathological variation in the HSD11B2 gene sequence. AB - 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) is a short-chain dehydrogenase/reductase (SDR) responsible for inactivating cortisol and preventing its binding to the mineralocorticoid receptor (MR). Nonfunctional mutations in HSD11B2, the gene encoding 11betaHSD2, cause the hypertensive syndrome of apparent mineralocorticoid excess (AME). Like other such Mendelian disorders, AME is rare but has nevertheless helped to illuminate principles fundamental to the regulation of blood pressure. Furthermore, polymorphisms in HSD11B2 have been associated with salt sensitivity, a major risk factor for cardiovascular mortality. It is therefore highly likely that sequence variation in HSD11B2, having subtle functional ramifications, will affect blood pressure in the wider population. In this study, a three-dimensional homology model of 11betaHSD2 was created and used to hypothesize the functional consequences in terms of protein structure of published mutations in HSD11B2. This approach underscored the strong genotype-phenotype correlation of AME: severe forms of the disease, associated with little in vivo enzyme activity, arise from mutations occurring in invariant alignment positions. These were predicted to exert gross structural changes in the protein. In contrast, those mutations causing a mild clinical phenotype were in less conserved regions of the protein that were predicted to be relatively more tolerant to substitution. Finally, a number of pathogenic mutations are shown to be associated with regions predicted to participate in dimer formation, and in protein stabilization, which may therefore suggest molecular mechanisms of disease. PMID- 20571119 TI - Isolated short CTG/CAG DNA slip-outs are repaired efficiently by hMutSbeta, but clustered slip-outs are poorly repaired. AB - Expansions of CTG/CAG trinucleotide repeats, thought to involve slipped DNAs at the repeats, cause numerous diseases including myotonic dystrophy and Huntington's disease. By unknown mechanisms, further repeat expansions in transgenic mice carrying expanded CTG/CAG tracts require the mismatch repair (MMR) proteins MSH2 and MSH3, forming the MutSbeta complex. Using an in vitro repair assay, we investigated the effect of slip-out size, with lengths of 1, 3, or 20 excess CTG repeats, as well as the effect of the number of slip-outs per molecule, on the requirement for human MMR. Long slip-outs escaped repair, whereas short slip-outs were repaired efficiently, much greater than a G-T mismatch, but required hMutSbeta. Higher or lower levels of hMutSbeta or its complete absence were detrimental to proper repair of short slip-outs. Surprisingly, clusters of as many as 62 short slip-outs (one to three repeat units each) along a single DNA molecule with (CTG)50*(CAG)50 repeats were refractory to repair, and repair efficiency was reduced further without MMR. Consistent with the MutSbeta requirement for instability, hMutSbeta is required to process isolated short slip-outs; however, multiple adjacent short slip-outs block each other's repair, possibly acting as roadblocks to progression of repair and allowing error-prone repair. Results suggest that expansions can arise by escaped repair of long slip-outs, tandem short slip-outs, or isolated short slip outs; the latter two types are sensitive to hMutSbeta. Poor repair of clustered DNA lesions has previously been associated only with ionizing radiation damage. Our results extend this interference in repair to neurodegenerative disease causing mutations in which clustered slip-outs escape proper repair and lead to expansions. PMID- 20571117 TI - Osmotically induced synthesis of the dipeptide N-acetylglutaminylglutamine amide is mediated by a new pathway conserved among bacteria. AB - The dipeptide N-acetylglutaminylglutamine amide (NAGGN) was discovered in the bacterium Sinorhizobium meliloti grown at high osmolarity, and subsequently shown to be synthesized and accumulated by a few osmotically challenged bacteria. However, its biosynthetic pathway remained unknown. Recently, two genes, which putatively encode a glutamine amidotransferase and an acetyltransferase and are up-regulated by osmotic stress, were identified in Pseudomonas aeruginosa. In this work, a locus carrying the orthologous genes in S. meliloti, asnO and ngg, was identified, and the genetic and molecular characterization of the NAGGN biosynthetic pathway is reported. By using NMR experiments, it was found that strains inactivated in asnO and ngg were unable to produce the dipeptide. Such inability has a deleterious effect on S. meliloti growth at high osmolarity, demonstrating the key role of NAGGN biosynthesis in cell osmoprotection. beta Glucuronidase activity from transcriptional fusion revealed strong induction of asnO expression in cells grown in increased NaCl concentration, in good agreement with the NAGGN accumulation. The asnO-ngg cluster encodes a unique enzymatic machinery mediating nonribosomal peptide synthesis. This pathway first involves Ngg, a bifunctional enzyme that catalyzes the formation of the intermediate N acetylglutaminylglutamine, and second AsnO, required for subsequent addition of an amide group and the conversion of N-acetylglutaminylglutamine into NAGGN. Interestingly, a strong conservation of the asnO-ngg cluster is observed in a large number of bacteria with different lifestyles, such as marine, symbiotic, and pathogenic bacteria, highlighting the ecological importance of NAGGN synthesis capability in osmoprotection and also potentially in bacteria host-cell interactions. PMID- 20571125 TI - (R)evolution of complex regulatory systems. AB - Signaling systems are exciting to study precisely because they are some of the most complex and dynamical systems that we know. The cell needs operational freedom and, thus, many motif-domain interactions might not be "hard-wired" through evolution, but instead may be like the Linux operating system, where symbolic links can point to files without duplication. PMID- 20571123 TI - Cost-of-illness of patients with systemic sclerosis in a tertiary care centre. AB - OBJECTIVE: The aim of our study was to assess the costs of SSc and to analyse cost drivers. METHODS: A cross-sectional survey of consecutive patients with SSc was performed in a rheumatology centre in Hungary. Clinical characteristics, the European Scleroderma Study Group activity index, disease severity scale (DSS), scleroderma HAQ (S-HAQ) and health care utilization were recorded. Cost calculation was performed and correlation with clinical variables was analysed. Results were compared with RA and PsA. RESULTS: Eighty patients were involved: 72 (90%) women, mean age (s.d.) 57.4 (9.6) years and disease duration of 6.2 (6.6) years and 25% of the cases had dcSSc. Mean total cost was 9619 (s.d. 6444) euros/patient/year with rate of indirect cost being 56%. Disability-related productivity loss (55.2%) and hospitalization (28.3%) were the highest among the cost items. Patients with dcSSc had significantly higher direct costs (P = 0.005) compared with the lcSSc subset. Disease activity showed significant correlation with total costs, DSS and S-HAQ with direct costs. SSc-related costs were higher than in matched RA and PsA cases. CONCLUSIONS: The cost-of-illness of SSc is high with a dominance of productivity loss related costs. Moreover, the disease activity is an important cost driver. PMID- 20571121 TI - Insights from studying the mutation-induced allostery in the M2 proton channel by molecular dynamics. AB - As an essential component of the viral envelope, M2 proton channel plays a central role in the virus replications and has been a key target for drug design against the influenza A viruses. The adamantadine-based drugs, such as amantadine and rimantadine, were developed for blocking the channel so as to suppress the replication of viruses. However, patients, especially those infected by the H1N1 influenza A viruses, are increasingly suffering from the drug-resistance problem. According to the findings revealed recently by the high-resolution NMR studies, the drug-resistance problem is due to the structural allostery caused by some mutations, such as L26F, V27A and S31N, in the four-helix bundle of the channel. In this study, we are to address this problem from a dynamic point of view by conducting molecular dynamics (MD) simulations on both the open and the closed states of the wild-type (WT) and S31N mutant M2 channels in the presence of rimantadine. It was observed from the MD simulated structures that the mutant channel could still keep open even if binding with rimantadine, but the WT channel could not. This was because the mutation would destabilize the helix bundle and trigger it from a compact packing state to a loose one. It is anticipated that the findings may provide useful insights for in-depth understanding the action mechanism of the M2 channel and developing more effective drugs against influenza A viruses. PMID- 20571127 TI - Infrared snake eyes: TRPA1 and the thermal sensitivity of the snake pit organ. AB - The pit organs of pit vipers, pythons, and boas are remarkable sensory devices that allow these snakes to detect infrared radiation emitted by warm-blooded prey. It has been theorized that this capacity reflects the pit organ's exceptional sensitivity to subtle fluctuations in temperature, but the molecules responsible for this extreme thermal resolution have been unknown. New evidence shows that pit organs respond to temperature using the warmth-activated cation channel TRPA1 (transient receptor potential ankyrin 1), a finding that provides a first glimpse of the underlying molecular hardware. The properties of these snake TRPA1s raise intriguing questions about the mechanisms responsible for the exceptional sensitivity of many biological thermoreceptors and about the evolutionary origins of these warmth-activated TRP channels. PMID- 20571122 TI - Early-stage invasive breast cancers: potential role of optical tomography with US localization in assisting diagnosis. AB - PURPOSE: To investigate the potential role of optical tomography in the near infrared (NIR) spectrum with ultrasonographic (US) localization as a means of differentiating early-stage cancers from benign lesions of the breast. MATERIALS AND METHODS: The protocol was approved by the institutional review boards and was HIPAA compliant; all participants signed an informed consent. One hundred seventy eight consecutive women (mean age, 52 years; range, 21-89 years) who underwent US guided biopsy were imaged with a hand-held probe consisting of a coregistered US transducer and an NIR imager. The lesion location provided by coregistered US was used to guide optical imaging. Light absorption was measured at two optical wavelengths. From this measurement, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration (tHb) and was correlated with core biopsy results. For patients diagnosed with carcinomas and followed up with subsequent excision, the tHb was correlated with pathologic parameters. RESULTS: There were two in situ carcinomas (Tis), 35 T1 carcinomas, 24 T2-T4 carcinomas, and 114 benign lesions. The mean maximum and mean average tHb of the Tis-T1 group were 102.0 micromol/L +/- 28.5 (standard deviation) and 71.9 micromol/L +/- 18.8, and those of the T2-T4 group were 100.3 micromol/L +/- 26.4 and 67.0 micromol/L +/- 18.3, respectively. The mean maximum and mean average tHb of the benign group were 55.1 micromol/L +/- 22.7 and 39.1 micromol/L +/- 14.9, respectively. Both mean maximum and mean average tHb levels were significantly higher in the malignant groups than they were in the benign group (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value for Tis-T1 cancers were 92%, 93%, 81%, and 97%. The corresponding values for T2-T4 tumors were 75%, 93%, 69%, and 95%. CONCLUSION: The angiogenesis (tHb) contrast imaged by using the NIR technique with US holds promise as an adjunct to mammography and US for distinguishing early-stage invasive breast cancers from benign lesions. PMID- 20571126 TI - Wnt signaling in axial patterning and regeneration: lessons from planaria. AB - Wnt signal transduction plays a crucial role in stem cell proliferation and regeneration. When canonical Wnt signaling is low, heads develop, and when it is high, tails are formed. In planarians, Wnt transcription is activated by wounding in a beta-catenin-independent way. Hedgehog is one of the signals involved, because it induces regeneration of tails (instead of heads) through the activation of Wnt transcription. Depletion of Smad4 blocks regeneration entirely, which suggests that the bone morphogenetic protein signaling pathway and the Wnt pathway are required for regeneration and body patterning. PMID- 20571128 TI - Nodal signaling recruits the histone demethylase Jmjd3 to counteract polycomb mediated repression at target genes. AB - Both intercellular signaling and epigenetic mechanisms regulate embryonic development, but it is unclear how they are integrated to establish and maintain lineage-specific gene expression programs. Here, we show that a key function of the developmentally essential Nodal-Smads2/3 (Smad2 and Smad3) signaling pathway is to recruit the histone demethylase Jmjd3 to target genes, thereby counteracting repression by Polycomb. Smads2/3 bound to Jmjd3 and recruited it to chromatin in a manner that was dependent on active Nodal signaling. Knockdown of Jmjd3 alone substantially reduced Nodal target gene expression, whereas in the absence of Polycomb, target loci were expressed independently of Nodal signaling. These data establish a role for Polycomb in imposing a dependency on Nodal signaling for the expression of target genes and reveal how developmental signaling integrates with epigenetic processes to control gene expression. PMID- 20571124 TI - RNase-assisted RNA chromatography. AB - RNA chromatography combined with mass spectrometry represents a widely used experimental approach to identify RNA-binding proteins that recognize specific RNA targets. An important drawback of most of these protocols is the high background due to direct or indirect nonspecific binding of cellular proteins to the beads. In many cases this can hamper the detection of individual proteins due to their low levels and/or comigration with contaminating proteins. Increasing the salt concentration during washing steps can reduce background, but at the cost of using less physiological salt concentrations and the likely loss of important RNA-binding proteins that are less stringently bound to a given RNA, as well as the disassembly of protein or ribonucleoprotein complexes. Here, we describe an improved RNA chromatography method that relies on the use of a cocktail of RNases in the elution step. This results in the release of proteins specifically associated with the RNA ligand and almost complete elimination of background noise, allowing a more sensitive and thorough detection of RNA-binding proteins recognizing a specific RNA transcript. PMID- 20571132 TI - The efficiency of clinical trial designs for predictive biomarker validation. AB - BACKGROUND: The rapid advance of molecular genetic technology and of molecular diagnostics companies have set the stage for a new era in personalized treatments. Biomarkers such as gene expressions may be integrated into the anatomically based tumor-node-metastasis staging system to provide information for risk stratification and treatment selection. With the assumption that preliminary results show evidence that a biomarker has predictive value, the marker-based designs are geared to assess the purported predictive value in a clinical trial. PURPOSE: In this article, we compared the efficiency of the traditional design, which does not involve a biomarker, to several alternative designs in terms of the sample size required in each trial. METHODS: We first derived the variance formulas for the two-sample t-tests under the various designs when the biomarker assay is imperfect, and then conducted numerical and simulation studies to evaluate the performance of the various designs. RESULTS: Based on numerical and simulation studies, we conclude that the marker-based strategy designs are less efficient than the traditional design in general. Since the biomarker assay is imperfect in a realistic setting, the estimated sample size for each alternative design is influenced by the sensitivity and specificity of the assay and the prevalence of the biomarker in the population of interest as well as the parameters involved in a standard sample size calculation. LIMITATIONS: Due to limitations of a simulation study, it is not clear whether our results can be generalized to other parameter settings that are different from the ones used in the simulation study. CONCLUSIONS: The marker-based strategy designs are less efficient than the traditional design in general. If there is no treatment effect among marker-negative patients, it is still feasible to use the marker-based strategy design I if the assay sensitivity is high. If the treatment effect among marker-negative patients is half of the effect among marker-positive patients, the marker prevalence must be relatively high and the sensitivity of the assay must be very high for the marker-based strategy design I to approximate the efficiency of the traditional design. The efficiency of the marker-based strategy design II relative to the traditional design is low in all scenarios considered under the current study. PMID- 20571134 TI - Assessing contamination and compliance in the prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. AB - BACKGROUND: Recently, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial published 7-year complete prostate cancer mortality results, which showed no benefit of screening with prostate specific antigen (PSA) and digital rectal examination (DRE). An issue of concern was the substantial level of 'contamination', or use of PSA and DRE in control arm men. PURPOSE: To provide a detailed description of contamination in PLCO. METHODS: Surveys inquiring about the most recent PSA and DRE use were given to a sample of control arm men throughout the screening phase of PLCO (years 0-5). A probability model was utilized to translate survey results into actual frequency counts of tests. To assess the impact of contamination, Surveillance, Epidemiology, and End RESULTS: (SEER) incidence rates from the pre-screening era (1985-1987) as well as contemporaneous rates, were applied to PLCO person-years of observation. Results Of 38,350 control arm men, 2427 were surveyed. Pre-trial screening and college education were statistically significantly associated with increased contamination rates. The estimated mean number of screening PSAs (DREs) in the control arm was 2.7 (1.1); this compares to 5.0 (3.5) in the screened arm. 1984 and 2538 prostate cancers were observed in the control and screened arms, respectively, during the screening phase. In the absence of screening, 960 and 949 would have been expected; with contemporaneous incidence rates, 1630 and 1611 were expected. LIMITATIONS: Due to the limitations of the surveys, in terms of both reach and scope, the exact level of PSA and DRE use in control arm men cannot be known. CONCLUSIONS: Use of prostate screening by control arm men was substantial, but also substantially less than in screened arm men. Detailed quantitative analyses of screening use across arms are critical for understanding current and future findings from the prostate component of PLCO. PMID- 20571130 TI - Bayesian adaptive randomization designs for targeted agent development. AB - BACKGROUND: With better understanding of the disease's etiology and mechanism, many targeted agents are being developed to tackle the root cause of problems, hoping to offer more effective and less toxic therapies. Targeted agents, however, do not work for everyone. Hence, the development of target agents requires the evaluation of prognostic and predictive markers. In addition, upon the identification of each patient's marker profile, it is desirable to treat patients with best available treatments in the clinical trial accordingly. METHODS: Many designs have recently been proposed for the development of targeted agents. These include the simple randomization design, marker stratified design, marker strategy design, efficient targeted design, etc. In contrast to the frequentist designs with equal randomization, we propose novel Bayesian adaptive randomization designs that allow evaluating treatments and markers simultaneously, while providing more patients with effective treatments according to the patients' marker profiles. Early stopping rules can be implemented to increase the efficiency of the designs. RESULTS: Through simulations, the operating characteristics of different designs are compared and contrasted. By carefully choosing the design parameters, types I and II errors can be controlled for Bayesian designs. By incorporating adaptive randomization and early stopping rules, the proposed designs incorporate rational learning from the interim data to make informed decisions. Bayesian design also provides a formal way to incorporate relevant prior information. Compared with previously published designs, the proposed design can be more efficient, more ethical, and is also more flexible in the study conduct. LIMITATIONS: Response adaptive randomization requires the response to be assessed in a relatively short time period. The infrastructure must be set up to allow timely and more frequent monitoring of interim results. CONCLUSION: Bayesian adaptive randomization designs are distinctively suitable for the development of multiple targeted agents with multiple biomarkers. PMID- 20571131 TI - A Bayesian adaptive design with biomarkers for targeted therapies. AB - BACKGROUND: Targeted therapies are becoming increasingly important for the treatment of various diseases. Biomarkers are a critical component of a targeted therapy as they can be used to identify patients who are more likely to benefit from a treatment. Targeted therapies, however, have created major challenges in the design, conduct, and analysis of clinical trials. In traditional clinical trials, treatment effects for various biomarkers are typically evaluated in an exploratory fashion and only limited information about the predictive values of biomarkers obtained. PURPOSE: New study designs are required, which effectively evaluate both the diagnostic and the therapeutic implication of biomarkers. METHODS: The Bayesian approach provides a useful framework for optimizing the clinical trial design by directly integrating information about biomarkers and clinical outcomes as they become available. We propose a Bayesian covariate adjusted response-adaptive randomization design, which utilizes individual biomarker profiles and patient's clinical outcomes as they become available during the course of the trial, to assign the most efficacious treatment to individual patients. Predictive biomarker subgroups are determined adaptively using a partial least squares regression approach. RESULTS: A series of simulation studies were conducted to examine the operating characteristics of the proposed study design. The simulation studies show that the proposed design efficiently identifies patients who benefit most from a targeted therapy and that there are substantial savings in the sample size requirements when compared to alternative designs. LIMITATIONS: The design does not control for the type I error in the traditional sense and a positive result should be confirmed by conducting an independent phase III study focusing on the selected biomarker profile groups. CONCLUSIONS: We conclude that the proposed design may serve a useful role in the early efficacy phase of targeted therapy development. PMID- 20571129 TI - Insights from the conduct of a device trial in older persons: low magnitude mechanical stimulation for musculoskeletal health. AB - BACKGROUND: Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Nonpharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies. METHODS: The VIBES (Vibration to Improve Bone Density in Elderly Subjects) study is a randomized, double-blind, sham-controlled trial of the efficacy of low magnitude, high frequency mechanical stimulation in 200 men and women aged 60 years and older with bone mineral density T-scores by dual X-ray absorptiometry between -1 and -2.5 at entry. Participants are healthy, cognitively intact residents of independent living communities in the Boston area who receive free calcium and Vitamin D supplements. They are randomly assigned to active or sham treatment and stand on their assigned platform once daily for 10 min. All platforms have adherence data collection software downloadable to a laptop computer. Adverse events are closely monitored. 174 participants were randomized and will be followed for 2 years. Almost all active subjects have attained 1 year of follow-up. Bone mineral density is measured by both dual X-ray absorptiometry and quantitative computed tomography at baseline and annually. The main analysis will compare mean changes from baseline in volumetric bone density by quantitative computed tomography in active and sham groups. Adherence and treatment effect magnitude will also be evaluated. Secondary analyses will compare changes in two biochemical markers of bone turnover as well as longitudinal comparisons of muscle and balance endpoints. RESULTS: The VIBES trial has completed its first year of data collection and encountered multiple challenges leading to valuable lessons learned about the areas of recruitment from independent living communities, deployment of multiuser mechanical devices using radio frequency identification cards and electronic adherence monitoring, organization of transportation for imaging at a central site, and the expansion of study aims to include additional musculoskeletal outcomes. CONCLUSIONS: These lessons will guide future investigations in studies of individuals of advanced age. PMID- 20571141 TI - Reliability and reproducibility of Kienbock's disease staging. AB - We evaluated the interobserver reliability and intraobserver reproducibility of the Lichtman et al. classification for Kienbock's disease by getting four observers with different experience to look at 70 sets of wrist radiographs at different points in time. These observers staged each set of radiographs. Paired comparisons of the observations identified an agreement in 63% of cases and a mean weighted kappa coefficient of 0.64 confirming interobserver reliability. The stage of the involved lunate was reproduced in 78% of the observations with a mean weighted kappa coefficient of 0.81 showing intraobserver reproducibility. This classification for Kienbock's disease has good reliability and reproducibility. PMID- 20571140 TI - Induced lactation and exclusive breast milk feeding of adopted premature twins. AB - The authors report the first published case of premature twins whose adoptive mother induced lactation. Both infants are receiving exclusively human milk (adoptive mother's milk) at 2 months of age. This remarkable achievement reflects careful planning by the adoptive mother beginning in the prenatal period, her active role during the infants' hospital stay, and support from health care personnel and family members. Health care professionals are encouraged to support any adoptive mother who expresses interest in breastfeeding her infant(s). PMID- 20571133 TI - A clinical trial of peer-based culturally responsive person-centered care for psychosis for African Americans and Latinos. AB - BACKGROUND: Providing culturally competent and person-centered care is at the forefront of changing practices in behavioral health. Significant health disparities remain between people of color and whites in terms of care received in the mental health system. Peer services, or support provided by others who have experience in the behavioral health system, is a promising new avenue for helping those with behavioral health concerns move forward in their lives. PURPOSE: We describe a model of peer-based culturally competent person-centered care and treatment planning, informed by longstanding research on recovery from serious mental illness used in a randomized clinical trial conducted at two community mental health centers. METHODS: Participants all were Latino or African American with a current or past diagnosis within the psychotic disorders spectrum as this population is often underserved with limited access to culturally responsive, person-centered services. Study interventions were carried out in both an English-speaking and a Spanish-speaking outpatient program at each study center. Interventions included connecting individuals to their communities of choice and providing assistance in preparing for treatment planning meetings, all delivered by peer-service providers. Three points of evaluation, at baseline, 6 and 18 months, explored the impact of the interventions on areas such as community engagement, satisfaction with treatment, symptom distress, ethnic identity, personal empowerment, and quality of life. CONCLUSIONS: Lessons learned from implementation include making cultural modifications, the need for a longer engagement period with participants, and the tension between maintaining strict interventions while addressing the individual needs of participants in line with person-centered principles. The study is one of the first to rigorously test peer supported interventions in implementing person-centered care within the context of public mental health systems. PMID- 20571138 TI - Protective effect of Ginkgo biloba extract on liver damage by a single dose of CCl(4) in male rats. AB - Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl(4); 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl(4) significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 +/- 1044%) and aspartate aminotransferase (AST; 6964 +/- 833%), compared to control rats; CCl(4) also significantly decreased serum concentration of albumin (23 +/- 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 +/- 33%). Furthermore, CCl(4) down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl(4) produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl(4): significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl(4)-treated rats; GbE partially prevented the increase of liver MDA (55 +/- 14%) and the decrease of albumin concentration to 12 +/- 0.2%. This pretreatment prevented the down-regulation of TNF-a and up regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl(4) treated rats. PMID- 20571136 TI - Successful subject recruitment for a prostate cancer behavioral intervention trial. AB - BACKGROUND: Inadequate participant recruitment, which may lead to unrepresentative study samples that threaten a study's validity, is often a major challenge in the conduct of research studies. PURPOSE: The purpose of this article is to describe the development and implementation of a recruitment plan and evaluate the different recruitment strategies for a prostate cancer behavioral intervention trial. METHODS: Our recruitment plan was based on a framework (The Heiney-Adams Recruitment Model) that we developed, which combines relationship building and social marketing. We evaluated the success of our model using several different recruitment sources including: mailed letters, physician referral, and self-referral. RESULTS: Recruitment rates ranged from 67% for a support services department mailing to 100% for physician referral. While our original list of contacted patients was comprised of only 13% African American (AA) men, 22% of our recruited participants were AA. LIMITATIONS: One of the strongest barriers to recruitment was strict patient eligibility. Another significant barrier was the lack of electronic records systems to allow for the identification of large numbers of potential participants. CONCLUSIONS: In conclusion, our model incorporating social marketing and relationship building was quite successful in recruiting for a prostate cancer behavioral study, particularly AA participants. In developing strategies, future researchers should attend to issues of staffing, financial resources, physician support, and eligibility criteria in the light of study accrual. PMID- 20571142 TI - The microvacuolar system: how connective tissue sliding works. AB - The term 'fascia' has been applied to a large number of very different tissues within the hand. These range from aligned ligamentous formations such as the longitudinal bands of the palmar fascia or Grayson's and Cleland's ligaments, to the loose packing tissues that surround all of the moving structures within the hand. In other parts of the body the terms 'superficial' and 'deep fascia' are often used but these have little application in the hand and fingers. Fascia can be divided into tissues that restrain motion, act as anchors for the skin, or provide lubrication and gliding. Whereas the deep fascia is preserved and easily characterized in anatomical dissection, the remaining fascial tissue is poorly described. Understanding its structure and dynamic anatomy may help improve outcomes after hand injury and disease. This review describes the sliding tissue of the hand or the 'microvacuolar system' and demonstrates how movement of tissues can occur with minimal distortion of the overlying skin while maintaining tissue continuity. PMID- 20571135 TI - Evaluation of an automated method to assist with error detection in the ACCORD central laboratory. AB - BACKGROUND: Errors in clinical laboratory data are rare but their potential high cost both in terms of harm to the subject as well as diluted statistical power results in a significant workload for experts, who must review large volumes of data in the search for these errors. PURPOSE: The current research objective is to develop and evaluate a method to assist in detecting potential errors in laboratory data for an interventional clinical trial, such as Action to Control Cardiovascular Risk in Diabetes, where treatment effects may be influenced by errors in the data. METHODS: Utilizing data from a clinical trial investigating the effect of intensive glycemic control on major cardiovascular disease events, we constructed an algorithm that conducts probabilistic error detection called a 'Bayesian network'. Using a synthetic error model, errors were introduced into a testing dataset, and the Bayesian network's performance in identifying those errors was compared to laboratory experts. For each laboratory result we used the Bayesian network to compute the probability, the measured value was erroneous. This probability was then used to compute a receiver operating characteristic (ROC) curve. Three laboratory experts were recruited and took a survey consisting of 200 laboratory results. The task was to evaluate if these results were erroneous or not and to provide a confidence rating on a 6-point subjective probability scale. RESULTS: The Bayesian network's overall area under the ROC curve was calculated to be 0.79, whereas the three laboratory experts had areas under the ROC curve of 0.73, 0.73, and 0.72. Perfect error prediction and random guessing yield a ROC of 1.00 and 0.50, respectively. This difference in performance was statistically significant for all three experts. Human experts were also generally overconfident in their ability to detect errors. LIMITATIONS: The model is, by design, specific to a novel intervention in a specific diabetic population and, therefore, the specific Bayesian network discussed may not generalize to other interventions and populations. In addition, the study is limited by the small number of expert eligible to complete the survey. CONCLUSIONS: The results of this study suggest that continuous Bayesian networks, suitably constructed, may serve as an effective tool to assist experts in the review of voluminous laboratory data by flagging unlikely results for more thorough review. PMID- 20571146 TI - Increased presence of stromal myofibroblasts and tenascin-C with malignant progression in canine mammary tumors. AB - The aims of this study were to determine whether the appearance of stromal myofibroblasts and the expression of tenascin-C (Tn-C) correlate with the grade of malignancy in canine mammary tumors and to determine the main cellular source of Tn-C in these tumors. Single or double immunostaining using antibodies against alpha-smooth muscle actin (alpha-SMA) and Tn-C was performed on serial sections of normal canine mammary glands as well as those with lobular hyperplasia, simple adenoma, and simple carcinoma. Thirty-nine of 42 simple carcinomas (93%) exhibited stromal alpha-SMA-positive myofibroblasts and Tn-C expression. Only 6 of 11 cases of simple adenoma (55%) showed these changes, whereas no changes were observed in normal mammary gland tissue or cases of lobular hyperplasia. The distribution of stromal Tn-C correlated with the presence of myofibroblasts. However, Tn-C immunoreactivity was also occasionally observed in the basement membrane zone surrounding the myoepithelial layer in normal tissue, benign lesions, and tubulopapillary carcinomas. This pattern of staining was not related to the presence of myofibroblasts. The appearance of stromal myofibroblasts and expression of Tn-C were significantly correlated with higher histological grades of malignancy and vascular/lymphatic invasion in simple carcinomas. Stromal myofibroblasts appear to be a major cellular source of Tn-C and play an important role in the development of canine mammary tumors. The Tn-C expressed in the basement membrane zone of normal, hyperplastic, and neoplastic mammary tissue, which is likely produced by neighboring myoepithelial cells, may differ functionally from the Tn-C produced by myofibroblasts. PMID- 20571143 TI - Placebo, prozac and PLoS: significant lessons for psychopharmacology. AB - Kirsch et al. (2008, Initial severity and antidepressant benefits: a meta analysis of data submitted to the Food and Drug Administration. PLoS Med 5: e45), conducted a meta-analysis of data from 35 placebo controlled trials of four newer antidepressants. They concluded that while these drugs are statistically significantly superior to placebo in acute depression, the benefits are unlikely to be clinically significant. This paper has attracted much attention and debate in both academic journals and the popular media. In this critique, we argue that Kirsch et al.'s is a flawed analysis which relies upon unusual statistical techniques biased against antidepressants. We present results showing that re analysing the same data using more appropriate methods leads to substantially different conclusions. However, we also believe that psychopharmacology has lessons to learn from the Kirsch et al. paper. We discuss issues surrounding the interpretation of clinical trials of antidepressants, including the difficulties of extrapolating from randomized controlled trials to the clinic, and the question of failed trials. We call for more research to establish the effectiveness of antidepressants in clinically relevant populations under naturalistic conditions, for example, in relapse prevention, in patients with co morbidities, and in primary care settings. PMID- 20571145 TI - Immunohistochemical identification of collagen in the equine lung. AB - Recurrent airway obstruction (RAO) in the horse is a disease characterized by reversible bronchoconstriction and by mucus and neutrophil accumulation in the airways. It has been hypothesized that in horses with RAO, remodeling changes occur that are similar to those described in humans with asthma. Although collagen fibrils are present surrounding normal airways, they are a prominent feature of airway remodeling in human asthma with evidence of enhanced collagen III and I fibril deposition. An immunolabeling method was developed to identify collagen I and III in equine lung and to describe the collagen fiber type and distribution within the walls of the noncartilagenous bronchioles. The health status of 14 horses was characterized by clinical respiratory exam, bronchoalveolar lavage cytology, and pulmonary function tests. Following postmortem examination and histological assessment, horses were divided into RAO affected (n = 4) and nonaffected (n = 10) groups. Eight sections per horse from all lung regions were evaluated histologically. Results of the study showed that collagens I and III were present in the lamina propria and adventitial area of the noncartilaginous bronchioles. There was clear staining differentiation between collagen I or III, airway smooth muscle, and the airway epithelium. Collagen I and III were present in the lamina propria and adventitial areas of the noncartilaginous bronchioles of horses, and there was no significant difference in the relative amount of collagen I and III between this group of RAO affected and nonaffected horses. PMID- 20571147 TI - Longitudinal study of clinicopathological features of Johne's disease in sheep naturally exposed to Mycobacterium avium subspecies paratuberculosis. AB - The objective of this study was to describe chronological changes in infection status and enteric lesions of sheep naturally exposed to Mycobacterium avium subspecies paratubercuolosis. Samples of terminal ileum (TI) and mesenteric lymph node (MLN) were collected from 77 Merino sheep via surgical biopsy at 12, 18, and 24 months of age and necropsy at 36 months of age. Infection status at each sampling period was determined by fecal, TI, and MLN culture. Quantitative grading schemes were used to gauge the severity of granulomatous inflammation and degree of mycobacterial colonization affecting TI and MLN sections. Incidences of infection and disease were steady throughout the study; 46 of the 77 (59.7%) sheep became infected, and 30 of the 77 (39.0%) developed Johne's disease. Infection was first detected after 18 months of age in many sheep, and age when infection was first detected was not associated with clinical outcome. Culture of MLN detected 44 of the 46 (95.6%) infected sheep and initial lesions always involved MLN. Sheep typically developed lesions within 6-12 months following detection of infection by culture. The severity of enteritis and mycobacterial colonization progressed at variable rates among sheep. Severe multibacillary enteritis never regressed, and affected sheep expressed clinical signs within the following 12 months. Lymphocyte-rich paucibacillary enteritis was observed in 3 sheep, causing clinical signs in one and progressing to severe multibacillary enteritis in another. Six of the 46 (8.7%) biopsy-culture-positive sheep later had negative cultures at necropsy, suggesting recovery from infection. Further study is needed to identify factors associated with clearance of infection or progression of disease. PMID- 20571144 TI - Using insulin pump therapy in poorly controlled type 2 diabetes. AB - PURPOSE: The purpose of this pilot/feasibility study was to evaluate the use of insulin regimens among individuals with poorly controlled type 2 diabetes. In addition, a secondary aim was to build the body of evidence regarding the use of insulin pumps in patients with type 2 diabetes. METHODS: The setting was a suburban private endocrinology practice. Patients were a convenience sample of 15 adults, aged 40 to 64 years with poorly controlled type 2 diabetes, as defined by a hemoglobin A1C (A1C) of 8% or higher when continuous subcutaneous insulin infusion (CSII) was initiated. Baseline, 3-month, 6-month, and 1-year A1C, body mass index (BMI), basal and bolus insulin use, and number of office visits were collected through medical record review. Descriptive, independent, and paired t tests were used to evaluate data. RESULTS: A significant reduction in basal insulin use was found. Significant reductions in A1Cs were found at 3 months, 6 months, and 1 year. A significant increase in BMI was noted. CONCLUSIONS: Results indicated improvement in glycemic control with CSII for some patients with an associated increase in BMI. Reduction of basal insulin use was significant and, for some, cost effective using CSII. Current policies regarding CSII use in patients with type 2 diabetes need to be re-evaluated. PMID- 20571137 TI - Retention strategies and predictors of attrition in an urban pediatric asthma study. AB - BACKGROUND: The Urban Environment and Childhood Asthma (URECA) study is a multicenter prospective birth cohort study designed to examine factors related to the development of childhood asthma and allergies in an inner-city population. The retention of these participants has been challenging due to high mobility, inconsistent phone service, custody issues, and stressful life situations. PURPOSE: In this article, we describe the specific retention challenges we encountered during the first 2 years of follow-up in URECA and the strategies we utilized to address them. We also examine how selected maternal characteristics and other factors are related to retention and missed study visits. METHODS: Strategies implemented to engage participants included: collecting updated and alternative contact information, after-hours phone calls to participants, culturally competent staff, flexible study event scheduling, clinic visit transportation, quarterly newsletters, retention events, drop-in home visits, and cell phone reimbursements. An internally developed web-based data management system enabled close monitoring by site teams and the coordinating center. The rate of deactivations was calculated using survival analysis. Characteristics of active and deactivated participants were compared using the chi-squared test with a Cochran-Mantel - Haenszel adjustment for study site. The proportion of missed visits of the total expected in the first 2 years was calculated and compared by family characteristics using an ANOVA model or a trend test controlling for study site. All analyses were performed using SAS version 9.1 (Cary, NC). RESULTS: The 2-year retention rate was 89%. Participation in the first study event predicted subsequent engagement in study activities. Mothers who did not complete the first visit were more likely to miss future events (46.1% vs. 8.9%, p<0.0001) and to be deactivated (38.5% vs. 4.5%, p<0.0001). Mothers under 18 years of age were more likely to leave the study compared to older mothers (22.7% vs. 10.1%, p = 0.02). Also, mothers who were married missed fewer events than those not married (8.8% vs. 15.6%, p = 0.01). In addition, deactivations were more common when the child had entered daycare by 3 months of age (10.9% vs. 3.6%, p = 0.05). LIMITATIONS: The URECA population is predominantly minority, thus our findings might not be generalizable to other populations. Furthermore, we may not be able to observe the effects that might exist in a more diverse population. For example, 86% of the mothers are unmarried, making it difficult to reliably examine the effect of marital status. CONCLUSION: In research, successfully engaging and retaining participants is essential for achieving the study objectives. Identifying factors related to missed visits and deactivations are the initial step in recognizing the potential at-risk participants and can enable the design of targeted strategies to retain participants. PMID- 20571148 TI - Home and community composting for on-site treatment of urban organic waste: perspective for Europe and Canada. AB - As a result of urbanization and economic prosperity, which has accelerated the generation of municipal solid waste (MSW) along with its organic fraction, the management of MSW is a challenge faced by urban centres worldwide, including the European Union (EU) and Canada. Within a concept of waste recovery, the source separation and on-site treatment of urban organic waste (UOW) can resolve some of the major economic issues faced by urban centres along with the environmental and social issues associated with landfilling. In this context and in a comparison with the traditional landfilling practice, this paper examines on-site UOW composting strategies using a combination of centralized composting facilities, community composting centres and home composting. This study consisted of a feasibility and economic study based on available data and waste management costs. The results indicate that on-site treatment of UOW using practices such as home and community composting can lower management costs by 50, 37 and 34% for the rich European countries (annual GDP over US$25,000), the poorer European countries (annual GDP under US$25 000), and Canada, respectively. Furthermore, on site composting can reduce greenhouse gas emissions by 40% for Europe and Canada, despite gas capture practices on landfill sites. However, the performance of home composters and the quality of the compost products are issues to be further addressed for the successful implementation of UOW on-site composting. PMID- 20571150 TI - Global climate change and tree nutrition: effects of elevated CO2 and temperature. AB - Although tree nutrition has not been the primary focus of large climate change experiments on trees, we are beginning to understand its links to elevated atmospheric CO2 and temperature changes. This review focuses on the major nutrients, namely N and P, and deals with the effects of climate change on the processes that alter their cycling and availability. Current knowledge regarding biotic and abiotic agents of weathering, mobilization and immobilization of these elements will be discussed. To date, controlled environment studies have identified possible effects of climate change on tree nutrition. Only some of these findings, however, were verified in ecosystem scale experiments. Moreover, to be able to predict future effects of climate change on tree nutrition at this scale, we need to progress from studying effects of single factors to analysing interactions between factors such as elevated CO2, temperature or water availability. PMID- 20571151 TI - Drought-induced photosynthetic inhibition and autumn recovery in two Mediterranean oak species (Quercus ilex and Quercus suber). AB - Responses of leaf water relations and photosynthesis to summer drought and autumn rewetting were studied in two evergreen Mediterranean oak species, Quercus ilex spp. rotundifolia and Quercus suber. The predawn leaf water potential (Psi(lPD)), stomatal conductance (gs) and photosynthetic rate (A) at ambient conditions were measured seasonally over a 3-year period. We also measured the photosynthetic response to light and to intercellular CO2 (A/PPFD and A/C(i) response curves) under water stress (summer) and after recovery due to autumn rainfall. Photosynthetic parameters, Vc(max), J(max) and triose phosphate utilization (TPU) rate, were estimated using the Farquhar model. RuBisCo activity, leaf chlorophyll, leaf nitrogen concentration and leaf carbohydrate concentration were also measured. All measurements were performed in the spring leaves of the current year. In both species, the predawn leaf water potential, stomatal conductance and photosynthetic rate peaked in spring, progressively declined throughout the summer and recovered upon autumn rainfall. During the drought period, Q. ilex maintained a higher predawn leaf water potential and stomatal conductance than Q. suber. During this period, we found that photosynthesis was not only limited by stomatal closure, but was also downregulated as a consequence of a decrease in the maximum carboxylation rate (Vc(max)) and the light-saturated rate of photosynthetic electron transport (J(max)) in both species. The Vc(max) and J(max) increased after the first autumnal rains and this increase was related to RuBisCo activity, leaf nitrogen concentration and chlorophyll concentration. In addition, an increase in the TPU rate and in soluble leaf sugar concentration was observed in this period. The results obtained indicate a high resilience of the photosynthetic apparatus to summer drought as well as good recovery in the following autumn rains of these evergreen oak species. PMID- 20571154 TI - Physical activity measurement among individuals with disabilities: a literature review. AB - This review examined the literature on physical activity measurement among individuals with disabilities utilizing Yun and Ulrich's (2002) view on measurement validity. Specific inclusion criteria were identified. The search produced 115 articles; however, only 28 met all specified criteria. Findings revealed that self-reports and accelerometers were the most common approaches to measuring physical activity, and individuals with orthopedic impairments, those with mental retardation, and those with other health impairments received the most attention. Of the 28 articles, 17 (61%) reported validity and reliability evidence. Among those studies reporting validity, criterion-related evidence was the most common; however, a number of methodological limitations relative to validity were observed. Given the importance of using multiple physical activity measures, only five (18%) studies reported the use of multiple measures. Findings are discussed relative to conducting future physical activity research on persons with disabilities. PMID- 20571149 TI - Mucosal melanomas: a case-based review of the literature. AB - Mucosal melanoma is a rare cancer that is clearly distinct from its cutaneous counterpart in biology, clinical course, and prognosis. Recent studies have shown important differences in the frequencies of various genetic alterations in different subtypes of melanoma. Activating mutations in the c-KIT gene are detected in a significant number of patients with mucosal melanoma. This observation has resulted in the initiation of several clinical trials aimed at exploring the role of receptor tyrosine kinases that inhibit c-KIT in this patient population. We herein present a comprehensive literature review of mucosal melanoma along with case vignettes of a number of pertinent cases. We further discuss melanomas of the head and neck, the female genital tract, and the anorectum, which are the three most common sites of mucosal melanoma, with a particular focus on the diagnostic, prognostic, and therapeutic data available in the literature. PMID- 20571152 TI - Celiac disease in children and adolescents with autoimmune hepatitis: a single centre experience. AB - OBJECTIVES: Celiac disease (CD) is increasingly reported from North Africa, including Egypt. Autoimmune hepatitis (AIH) is considered a high risk factor for CD. We aimed to investigate the frequency of CD diagnosis in AIH. METHODS: We prospectively enrolled 26 AIH patients aged 3.5-21 (mean 9.98 +/- 3.94) years and 20 healthy age- and sex-matched controls. Serodiagnosis of CD was based on the most sensitive tests namely immunoglobulin A (IgA) human tissue transglutaminase antibody (IgA-tTGA) by enzyme-linked immunosorbent assay and/or IgA endomysial antibody (IgA-EMA) by immunofluoresence and confirmed the diagnosis by upper gastrointestinal endoscopy and histo-pathological findings in jejunal biopsy. RESULTS: IgA-EMA was positive in four patients (15.4%), whereas IgA-tTGA was positive in two of them (7.7%). Histopathology was confirmatory in three (11.5%) seropositive patients. CONCLUSION: The high prevalence (11.5%) of CD among Egyptian children with AIH indicates that CD exists in high-risk groups in our region and must be carefully looked into. PMID- 20571153 TI - Malabsorption syndrome and leukotriene inhibitor. AB - Previously described treatments used for eosinophilic diseases of the gastrointestinal tract have included dietary restrictions primarily of cow milk protein, anti-inflammatory therapy utilizing suplatast, budesonide and corticosteroids, cromolyn sodium, anti-histamines and oral inhalable steroids. We describe a 12-year-old girl with diarrhea and malabsorption, who was later diagnosed to have eosinophilic gastroenteritis, was unresponsive to standard therapies, but exhibited marked improvement with use of montelukast. PMID- 20571155 TI - The psychometric properties of the difficult behavior self-efficacy scale. AB - The study was designed to estimate the psychometric properties of Hastings and Brown's (2002a) Difficult Behavior Self-efficacy Scale. Participants were two samples of physical educators teaching in Korea (n=229) and the United States (U.S.; n=139). An initial translation of the questionnaire to Korean and pilot study were conducted along with the larger study using a confirmatory factor analysis procedure. Internal consistency estimates (weighed Omega) for the five item scale were 0.88 both the Korean and U.S. samples. The average variances extracted for the one factor were 0.59 for the total data set and 0.57 each for the Korean and U.S. samples. Confirmatory factor analysis supported a five-item, unidimensional model for self-efficacy for the total sample: Goodness of Fit Index (GFI)=0.97, Nonnormed Fit Index (NNFI)=0.95, Comparative Fit Index (CFI)=0.98, and Standardized Root Mean Square Residual (SRMR)=0.03. Only the Root Mean Square Error of Approximation (RMSEA=0.12) fell below criterion levels of acceptable fit, with similar fit indices occurring in separate analyses of the Korean and U.S. samples. Invariance testing across the two samples supported metric invariance (similarity of factor loadings) but not scalar invariance (U.S. means higher on all five items). The factor structure for the self-efficacy scale provides an initial estimate of validity and internal consistency for use with different teacher groups. PMID- 20571156 TI - Haptic stabilization of posture in adults with intellectual disabilities using a nonrigid tool. AB - This study assessed the effects of haptic information on the postural control systems of individuals with intellectual disabilities (ID), through the use of a nonrigid tool that we call the "anchor system" (e.g., ropes attached to graduated weights that rest on the floor). Eleven participants with ID were asked to stand, blindfolded, on a balance beam placed at two heights (10 and 20 cm), for 30 s, while using the anchor system at two weights. The lighter anchor weight appeared to improve the individuals' balance in contrast to a control task condition; therefore, we concluded that haptic sensitivity was more significant in helping to orient the body than was the anchor's mechanical support alone. PMID- 20571157 TI - Cycling for students with ASD: self-regulation promotes sustained physical activity. AB - Individuals with autism often lack motivation to engage in sustained physical activity. Three adolescents with severe autism participated in a 16-week program and each regularly completed 30 min of cycling at the end of program. This study investigated the effect of a self-regulation instructional strategy on sustained cycling, which included self-monitoring, goal setting, and self-reinforcement. Of particular interest was the development of self-efficacy during the physical activity as a mediator of goal setting. A multiple baseline changing criterion design established the effectiveness of the intervention. The results suggest that self-regulation interventions can promote sustained participation in physical activity for adolescents with severe autism. PMID- 20571158 TI - The ability of elite table tennis players with intellectual disabilities to adapt their service/return. AB - In this study the ability of elite table tennis players with intellectual disability (ID) to adapt their service/return to specific ball spin characteristics was investigated. This was done by examining the performance of 39 players with ID and a reference group of 8 players without ID on a standardized table tennis specific test battery. The battery included 16 sets of 15 identical serves that had to be returned to a fixed target, and two additional tests measuring reaction time and upper limb speed. A 2 x 4 ANOVA (with group and type of spin as independent variables) with repeated measurements (15 consecutive returns) supported the hypothesis that elite table tennis players with ID were significantly less proficient than their counterparts without ID, but both groups demonstrated a comparable progression in learning. Spearman correlation coefficients indicated a positive relationship between accuracy of return and upper limb speed (rho = 0.42: p < .05) and reaction time (rho = 0.41: p < .05), showing that these generic factors are useful in partially explaining skill variations in specific sports. PMID- 20571160 TI - Legionella - a case for culture. PMID- 20571159 TI - Nutrition security in India: who exactly is in charge? PMID- 20571161 TI - Cutaneous zygomycosis : major concerns. PMID- 20571162 TI - Molecular & genetic factors contributing to insulin resistance in polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of unknown etiology. Insulin resistance is very common and plays a central pathogenic role in PCOS. During last decade several studies have been conducted to understand the mechanisms contributing to the state of insulin resistance and insulin-induced hyperandrogenemia in PCOS. Insulin signaling pathways have been dissected in different insulin responsive tissues such as skeletal muscles, adipose tissues, fibroblasts as well as ovaries to elucidate the mechanism. These studies suggest a post receptor signaling defect where metabolic action of insulin is affected but not the steroidogenic and mitogenic actions. Despite advancement in these studies gaps exist in our understanding of the mechanism of insulin resistance as well as insulin- induced steroidogenesis in PCOS. The syndrome is now considered as a complex multigenic disorder. Efforts are ongoing to dissect the variants of genes from multiple logical pathways which are involved in pathophysiology of the syndrome. But still today no gene has been emerged as universally accepted susceptibility gene for PCOS. This review briefly describes the lacunae along with the current status of molecular events underlying insulin resistance and the contribution of insulin signaling pathway genes in pathogenesis of PCOS along with future researchable areas. PMID- 20571163 TI - Isolation of Legionella pneumophila from clinical & environmental sources in a tertiary care hospital. AB - BACKGROUND & OBJECTIVES: Legionella pneumophila and other members of this genus are important respiratory pathogens but legionellosis often remains a neglected and under reported condition. Hence, this study was done to find out the presence of this organism in patients admitted to a tertiary care hospital with community acquired pneumonia (CAP). METHODS: A total of 470 lower respiratory tract samples and 24 water samples from hospital outlets were examined. Culture was done on buffered charcoal yeast extract agar with supplements and identification of the isolates was done by microscopy and biochemical tests. RESULTS: L. pneumophila could be isolated from 12 (2.55%) patients suffering from community-acquired lower respiratory tract infection, unassociated with other aetiological agents of bacterial pneumonia. Of the 24 water samples tested, 8 (33.3%) grew the same organism. INTERPRETATION & CONCLUSION: Our study has shown that Legionella is present in the hospital environment and was the aetiological agent of lower respiratory tract infection in 2.55 per cent of patients. A larger study and reports from other parts of the country may help in determining the true significance of legionellosis in India. PMID- 20571164 TI - Primary cutaneous zygomycosis from a tertiary care centre in north-west India. AB - BACKGROUND & OBJECTIVES: Zygomycosis is highly invasive fungal infection, with high mortality rate. In most of patients, diabetes mellitus is an underlying factor but in primary cutaneous zygomycosis, presentation may be different. Here we present the description of clinical presentation, fungi isolated and management of cases with cutaneous zygomycosis seen in a tertiary care hospital in north India during 2001-2007. METHODS: All patients diagnosed with primary cutaneous zygomycosis between November 2001 and September 2007 presenting with clinical diagnosis of necrotizing fasciitis were included. Detailed history of each patient was taken, clinical presentation, site of involvement, underlying illness and risk factor, if any were noted. The diagnosis was established by direct microscopic evidence of broad, aseptate or sparsely septate ribbon-like hyphae with right angle branching in KOH wet mount and histopathological examination of stained sections. Cultures were put up for fungal isolation and species identification. Outcome of the therapy was analysed. RESULTS: Of the nine patients reviewed, only one had diabetes mellitus. Commonest risk factor was injection abscess (33.3%). Apophysomyces elegans was isolated in four cases, Saksenaea vasiformis and Absidia corymbifera in one each. The fungal culture was sterile in three cases. Mortality rate was high with only four patients responded well to surgical and/or medical therapy. INTERPRETATION & CONCLUSION: Primary cutaneous zygomycosis appears to be on rise in India that calls for high index of clinical suspicion and an early biopsy of the affected area for timely diagnosis. The standard treatment is a combination of amphotericin B therapy, surgical debridement, and reversal of the underlying disease or immunosuppression. PMID- 20571165 TI - Induction of metalloproteinases expression by TLR ligands in human fibroblast like synoviocytes from juvenile idiopathic arthritis patients. AB - BACKGROUND & OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by chronic synovitis, cartilage damage and bone erosion. Both genetic and environmental factors and microbes probably play a role in pathogenesis. Microbes are recognized by Toll like receptors (TLRs) and activate innate immune response. We studied the ability of bacterial and viral products to produce matrix metalloproteinases (MMPs) and cytokines by fibroblast like synoviocytes (FLS) from patients with JIA. METHODS: FLS were cultured from synovial fluid (SF) of patients with JIA and subsequently stimulated for 48 h by different TLR ligands [peptidoglycan (PG) for TLR2, poly(I-C) for TLR3, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, imiquimod for TLR7 and CpG DNA for TLR9]. Later the production of IL6, IL8, MMP-1, MMP-3, tissue inhibitors of metalloproteinase (TIMP1) was measured in the culture supernatants by ELISA. Expression of TLR2, TLR4, TLR7 and TLR9 was studied in FLS derived from JIA patients by RT-PCR. RESULTS: IL6, IL8, MMP3 and MMP1 production was induced on stimulation of FLS with TLR2 ligand, TLR3 ligand, TLR4 ligand, TLR5 ligand but not with TLR7 ligand and TLR9 ligand. There was no effect of these ligands on the production of TIMP thus the balance was tilted in favour of MMPs after TLR ligation. TLR2, TLR4 and low expression of TLR9 was found but, no expression of TLR7 was found in FLS from JIA patients. INTERPRETATION & CONCLUSION: TLR pathway stimulation by microbial products or endogenous ligands could be involved in the production of MMPs in JIA and may contribute to disease pathology. Thus it may be beneficial to inhibit TLR pathway to reduce cartilage destruction. PMID- 20571166 TI - Total neuron numbers in CA1-4 sectors of the dog hippocampus. AB - BACKGROUND & OBJECTIVES: Early reports addressed morphological asymmetry in the cross-sectional width of the rat hippocampus. The present study was aimed at counting total number of neurons in CA1-4 sectors and the subiculum of the dog hippocampus as well as investigating possible left /right and male/female asymmetry. METHODS: Adult mongrel dogs (8 female and 5 male) were assessed by the right and left pawedness and sacrificed by exsanguinations. In each hippocampus dissected, the total neuron numbers of CAs and subiculum were estimated by the physical fractioning method. RESULTS: Significant hemispheric asymmetries were found in the number of pyramidal cells of CA1, CA3/2, CA4 and the subiculum. Sex difference was also found in the subiculum, in favour of the males. INTERPRETATION & CONCLUSION: Our study indicated a left dominant asymmetry in males and right dominancy in females as well as no functional asymmetry in specific regions of the dog hippocampus. Further investigations are necessary to verify the hypothesis that hippocampal morphological asymmetries in normal subjects are functionally related in memory or in cognitive skills. PMID- 20571170 TI - A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition. AB - BACKGROUND & OBJECTIVES: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. METHODS: Retrospective analysis of antiretroviral treatment (ART) naive adults started on highly active ART (HAART) from June 2006 to September 2008 was done. RESULTS: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. INTERPRETATION & CONCLUSION: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB- associated IRIS. PMID- 20571167 TI - Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats. AB - BACKGROUND & OBJECTIVES: A wealth of information concerning the essential role of renal sympathetic nerve activity (RSNA) in the regulation of renal function and mean arterial blood pressure homeostasis has been established. However, many important parameters with which RSNA interacts are yet to be explicitly characterized. Therefore, the present study aimed to investigate the impact of acute renal denervation (ARD) on sodium and water excretory responses to intravenous (iv) infusions of either norepinephrine (NE) or angiotensin II (Ang II) in anaesthetized spontaneously hypertensive rats (SHR). METHODS: Anaesthetized SHR were acutely denervated and a continuous iv infusion of NE (200 ng/min/ kg) or Ang II (50 ng/min/kg) was instigated for 1 h. Three 20-min urine clearances were subsequently collected to measure urine flow rate (UV) and absolute sodium excretion (U(Na)V). RESULTS: Higher UV and U(Na)V (P<0.05) were observed in denervated control SHR as compared to innervated counterparts. The administration of NE or Ang II to innervated SHR produced lower UV and U(Na)V (P<0.05 vs. innervated control SHR). Lower diuresis/natriuresis response to ARD was observed in NE-treated SHR compared to denervated control SHR (P<0.05). Salt and water excretions in denervated NE-treated SHR, however, were significantly higher (P<0.05) relative to the excretion levels in control denervated SHR. Conversely, there was a higher (all P<0.05) diuresis/natriuresis response to ARD when Ang II was administered to SHR compared to denervated control or innervated Ang II-treated SHR. INTERPRETATION & CONCLUSIONS: NE retains its characteristic antidiuretic/antinatriuretic action following ARD in SHR. Typical action of Ang II on salt and water excretions necessitates the presence of an intact renal innervation. Ang II is likely to facilitate the release of NE from renal sympathetic nerve terminals through a presynaptic site of action. Moreover, there is a lack of an immediate enhancement in the renal sensitivity to the actions of NE and Ang II following ARD in a rat model of essential hypertension. PMID- 20571169 TI - Investigation of the outbreak of typhoid in a village of Thar Desert Rajasthan, India. AB - BACKGROUND & OBJECTIVES: Outbreaks of typhoid have been reported from Maharashtra, Bangalore, West Bengal and Pondicherry in India but rarely from Rajasthan. We investigated an outbreak of typhoid in a village of Thar Desert of Rajasthan. METHODS: A retrospective cohort study was carried out during May-July 2007 in Varkana village, Pali district, Rajasthan, to identify the risk factor for disease. The information on outbreak was collected and then described in time, place and person characteristics to arrive at aetiological hypotheses. RESULTS: There were 219 cases of typhoid in village. Attack rate was 104 cases per 1000 population. Maximum attack rate of 276 cases per 1000 population was noted in persons of 10-14 yr age group. Forty three serum samples were reported positive for Widal agglutination test out of 70 tested. Drinking of water from government overhead tanks was associated with disease significantly (RR= 11.1, 95% CI= 3.7-33). Two of the three water samples from government tanks were found positive for faecal contamination. INTERPRETATION & CONCLUSION: The outbreak of typhoid in a village affected >200 persons of all age groups and both gender. Exposure to the drinking water from government tanks was found significantly associated with the disease. Preventive and control measures undertaken after analytical epidemiological study helped in terminating the outbreak. PMID- 20571171 TI - Anti-tuberculosis activity of selected medicinal plants against multi-drug resistant Mycobacterium tuberculosis isolates. AB - BACKGROUND & OBJECTIVES: Emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis has further complicated the problem of tuberculosis (TB) control. Medicinal plants offer a hope for developing alternate medicines for the treatment of TB. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Acalypha indica, Adhatoda vasica, Allium cepa, Allium sativum and Aloe vera. METHODS: Aqueous extracts of leaves of A. indica, A. vasica, bulbs of A. cepa, cloves of A. sativum and pure gel of A. vera leaves, were tested in vitro for their activity against two MDR isolates (DKU-156 and JAL-1236), reference susceptible strain M. tuberculosis H37Rv as well as rapid grower mycobacterial pathogen M. fortuitum (TMC-1529) using Lowenstein Jensen (L-J) medium and colorimetric BacT/ ALERT 3D system. Activity in L-J medium was evaluated by percentage inhibition which was calculated by mean reduction in number of colonies on extract containing as compared to extract free controls. RESULTS: Extracts of all the five plants A. indica, A. vasica, A. cepa, A. sativum and A. vera exhibited anti-tuberculosis activity in L-J medium, the proportion of inhibition of these plants extract in respect mentioned above is 95, 32, 37, 72, 32 per cent, respectively for MDR isolate DKU-156 and 68, 86, 79, 72, 85 per cent, respectively for another MDR isolate JAL-1236, while for sensitive M. tuberculosis H37Rv, inhibition was found to be 68, 70, 35, 63 and 41 per cent, at 4 per cent v/v concentration in L-J medium. There was no inhibition against rapid grower M. fortuitum (TMC-1529). In BacT/ALERT also, extracts of these plants showed significant inhibition against M. tuberculosis. INTERPRETATION & CONCLUSION: Our findings showed that all these plants exhibited activity against MDR isolates of M. tuberculosis. While the anti-TB activity of A. vera, A. vasica and A. sativum against MDR isolates confirm earlier results, activity of the extracts of A. indica and A. cepa is reported for the first time. Further studies aimed at isolation and identification of active substances from the extracts which exhibited promising activities, need to be carried out. PMID- 20571173 TI - Hypolipidaemic & hepatoprotective effects of Psidium guajava raw fruit peel in experimental diabetes. AB - BACKGROUND & OBJECTIVES: The study evaluated the hypolipidaemic and hepatoprotective effects of unripe Psidium guajava fruit peel aqueous extract in streptozotocin (STZ) induced severely diabetic rats by assaying their triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, alkaline phosphatase (ALKP), asperate amino transeferase (AST), alanine amino transferase (ALT) and creatanine (CRTN) levels. METHOD: Severely diabetic albino Wister rats of same age group were treated orally once a day upto 3wk with a dose of 400 mg/kg bw of lyophilized extract. TG, TC, HDL, ALKP, AST, ALT and CRTN were estimated. LDL and VLDL cholesterol levels were calculated from the above measurements by using Friedwald formula. RESULTS: A significant decrease in TG (P<0.01), TC (P<0.01), HDL (P<0.001) VLDL (P<0.001) and LDL (P<0.01), ALKP (P<0.01), AST (P<0.05), ALT (P<0.05) and CRTN (P<0.001) levels were observed after 21 days treatment of aquous extract of raw fruit peel compared to pre treatment levels. INTERPRETATION & CONCLUSION: The extract showed significant hypolipidaemic activity in addition to its hypoglycaemic and antidiabetic activity. In view of its relative non-toxic nature P. guajava raw fruit peel may be a potential antidiabetic agent. PMID- 20571174 TI - Monocationic surfactant induced ultra structural changes in antibiotic resistant Escherichia coli. AB - BACKGROUND & OBJECTIVES: Cetrimide is a monocationic surfactant, commonly used for disinfection of hospital floors, equipments, for cleansing of burns and wounds, hand wash, etc. We evaluated whether antibiotic resistant (AR) Escherichia coli isolates from hospital settings (nosocomial pathogens) show any evidence of significant reduction in their susceptibility to cetrimide. Also the response of AR E. coli (nosocomial pathogens) to the action of cetrimide was assessed by studying the ultra structural changes induced using transmission electron microscopy (TEM). METHODS: A total of 165 clinical samples were screened for isolation of E. coli. Eighty two (49.6%) samples were positive for E. coli. Antibiotic susceptibility testing of E. coli isolates was carried out by Kirby Bauer method to isolate AR E. coli. The randomly selected AR E. coli isolate was treated with different concentrations of cetrimide and minimum inhibitory concentration (MIC) of cetrimide was determined by broth micro dilution method. This same isolate was used for performing time kill assay and TEM study. RESULTS: The test E. coli isolate showed resistance to 12 different antibiotics. The MIC of cetrimide against AR E. coli was 312.5 microg/ml. The ultra cellular structural changes in cetrimide treated AR E. coli revealed vacuole formation, disaxilization of nuclear material, loss of cytoplasmic granularity, bleb formation and cell lysis. CONCLUSION: Ultra structural changes induced by the action of cetrimide revealed cell damaging changes in the AR E. coli to be dose and time dependent. The results showed that antibiotic resistance does not alter any change in susceptibility of E. coli to cetrimide, which was found to be still an effective disinfectant against a nosocomial pathogen E. coli. PMID- 20571177 TI - Species distribution & antifungal susceptibility of oral Candida colonising or infecting HIV infected individuals. PMID- 20571172 TI - In vitro estrogenic activities of fenugreek Trigonella foenum graecum seeds. AB - BACKGROUND & OBJECTIVES: Trigonella foenum graecum commonly known as fenugreek, has been widely cultivated in Asia, Africa and Mediterranean countries for the edible and medicinal values of its seeds. Earlier reports show that fenugreek seeds provide a mastogenic effect resulting in enhanced breast size. However, very little is known about its estrogenic effect. The present study investigated the effect of chloroform extracts of fenugreek seeds (FCE) in breast cancer cells for its estrogenic effect, and to assess its capacity as an alternative to hormone replacement therapy (HRT). METHODS: The effect of FCE on cell proliferation of estrogen receptor (ER) positive breast cancer cells, MCF-7 was studied by MTT assay at a concentration range of 20 to 320 microg/ml. The competitive ER binding assay (HAP assay) was done to find out the ER binding capacity of the extract. Transfection and reporter assay (DLR assay), and RT- PCR with an estrogen responsive gene pS2 were done to find out the transcriptional regulatory activity of FCE. RESULTS: FCE stimulated the proliferation of MCF-7 cells, showed binding to ER (IC(50) = 185.6 +/- 32.8 microg/ ml) and acted as an agonist for ER mediated transcription via ERE. It also induced the expression of estrogen responsive gene pS2 in MCF-7 cells. INTERPRETATION & CONCLUSION: Our study provided the evidence for estrogenic activities of fenugreek seeds. Further in vitro and in vivo studies could demonstrate its suitability as an alternative to HRT. PMID- 20571168 TI - Low serum zinc levels in an endemic area of visceral leishmaniasis in Bihar, India. AB - BACKGROUND & OBJECTIVES: India carries approximately 50 per cent of the global burden of visceral leishmaniasis and majority of patients from the poor, rural communities of Bihar State. Zinc is an essential trace element and its relevance for proper functioning of the entire immune system is already well documented. Though low serum zinc levels have been reported in many parasitic diseases, limited information is available regarding zinc status in human leishmaniasis. We investigated to define the relationship between zinc level in visceral leishmaniasis (VL) patients in endemic and non-endemic regions. METHODS: Venous blood was collected from 88 patients, 16 parasitologically confirmed VL, 35 healthy controls from endemic area (Bihar) and 37 healthy urban controls from non endemic area, Delhi. In all the three groups, levels of serum albumin, total protein (markers of nutritional status) and zinc were estimated by colorimetric methods. RESULTS: Serum zinc levels were found to be significantly lower (P<0.001) in VL patients than non-endemic controls. The serum zinc levels in VL endemic controls were also significantly lower (P<0.001) than non- endemic controls, but these values were not statistically significantly different from VL patients. However, all samples from Bihar (VL patients and controls) had lower serum zinc levels than non-endemic controls from Delhi. INTERPRETATION & CONCLUSION: Low serum Zn levels, in healthy subjects from Bihar and more significantly in VL patients of this region, are possibly associated with vulnerability and endemicity of visceral leishmaniasis in the region. Further studies need to be done to assess the role of oral zinc supplementation in better management and prevention of VL, particularly in endemic areas. PMID- 20571176 TI - Enhancement of the antibiotic activity of gentamicin by volatile compounds of Zanthoxylum articulatum. PMID- 20571178 TI - Structural imbalance and resource shortage in the Australian mental health sector. AB - BACKGROUND: Resource shortages and 'unmet need' are two economic problems reported in the Australian mental health sector. 'Unmet need' arises with a 'structural imbalance', the non-correspondence between the use of mental health services and the extent of need for those services. Another problem reported in literature is 'met non-need', people who use mental health services and do not have a diagnosis of mental illness. AIMS OF STUDY: To develop an approach to measure the resource shortage and the structural imbalance by using (i) data on consumers of mental health services ('service utilisation'), (ii) data on those who do not consume such services ('service non-utilisation'). These data are cross-classified with data on (i) people who do have a diagnosis of mental illness (proxy of 'need'), and (ii) people who do not have a diagnosis of mental illness (proxy of 'non-need'). METHOD: A conceptual framework (using 'polar' cases), which is often used in economics, is employed to define perfect 'structural balance' and perfect 'structural imbalance'. This framework allows the measurement of the degree of structural imbalance. Enumeration involves the cross-classified population sub-groups of 'need' and 'service utilisation' in tabular form, conceived of by reference to Yerushalmy's cross-classification approach for determining the sensitivity and specificity of diagnostic procedures in medicine. Venn diagrams are also applied for resource shortage evaluation. The study relies on the data of the Australian Bureau of Statistics 1997 epidemiological survey, the Australian national survey, Mental Health and Wellbeing: Profile of Adults. RESULTS: Clear evidence of resource insufficiency is found. The study shows also an extensive structural imbalance. A total of 1,477,500 subjects affected by mental disorders are found in the 'unmet need' category. This group (receiving no mental health services) represents 62 per cent of people with a diagnosis of mental disorder, and 11 per cent of the Australian population. On the other hand, a group of 591,600 people consume mental health services and do not meet the criteria of mental illness. This group is 4.4 per cent of the Australian population. DISCUSSION AND LIMITATIONS: In the absence of a measure of expenditure, this study adopted 'people' as a proxy for expenditure. The available data do not enable us to determine how much 'met non-need' is due to the 'Worried Well', or to those who use government-subsidised services for other reasons (sport, executive performance etc). IMPLICATIONS FOR HEALTH POLICIES: Commitment to quantification within the mental health sector is a relatively recent habit by the Australian Government. Policy formation often simply follows scandals to cope with adverse publicity and evidence-based policy is needed. Preliminary evidence of this study indicates resource insufficiency in the Australian mental health sector. This is a policy issue to be distinguished from the 'unmet need' and 'met non-need' arising from structurally imbalanced resource allocation. Separate policy targets require separate policy instruments. PMID- 20571175 TI - Burkholderia cepacia complex in septicaemic non-cystic fibrosis cases from two tertiary care hospitals in north India. PMID- 20571179 TI - Exercise and adolescent mental health: new evidence from longitudinal data. AB - BACKGROUND: Recent U.S. government recommendations state that increased physical activity can substantially improve adolescent psychological well-being. However, many of the studies upon which this conclusion is based did not adequately address the role of difficult-to-measure factors that could be correlated with both physical activity and adolescent mental health. AIM OF THE STUDY: The primary aim of this study is to estimate the effect of physical activity on adolescent psychological well-being controlling for the influence of unmeasured school- and individual-level confounding factors. METHODOLOGY: Drawing on data from the first two waves of the National Longitudinal Study of Adolescent Health, we use ordinary least squares to estimate the effect of physical activity and hours of inactivity on two psychometrically sound measures of psychological well being (the Center for Epidemiologic Studies Depression scale and the Rosenberg Self-Esteem scale). Next, we add school fixed effects and then individual fixed effects to the estimating equation in order to control for difficult-to-measure factors that could be correlated with both physical activity and adolescent mental health. RESULTS: Ordinary least squares (OLS) estimates show that a higher frequency of moderate or physical exercise is associated with improved psychological well-being for adolescents. This result is robust to the inclusion of school fixed effects, but when we control for fixed individual heterogeneity by first-differencing the data, the estimated effects of physical activity on depression and self-esteem decline sharply, often becoming small in magnitude or statistically indistinguishable from zero. We conclude that OLS estimates of the effect of physical activity on emotional health may be biased upwards. LIMITATIONS: While the nationally representative panel data we use is a rich source of information on mental health, our measure of physical activity is limited in that it fails to capture total time spent exercising. Moreover, while our statistical approach controls for time-invariant unobservables, we cannot rule out the possibility of time-varying unobserved confounders. IMPLICATIONS: Although policy interventions designed to promote more exercise among youths may have important physical health benefits, our findings suggest that the short-run emotional benefits are likely small and concentrated at higher frequencies of physical activity. FUTURE RESEARCH: To enhance the internal validity of research in this area, future work could tackle the difficult challenge of identifying exogenous variation in physical exercise using a natural experiment approach. PMID- 20571180 TI - Economic outcomes of eszopiclone treatment in insomnia and comorbid major depressive disorder. AB - BACKGROUND: Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually. AIMS OF THE STUDY: The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD. METHODS: Data from 434 patients enrolled in an 8-week clinical trial who met the economic subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price. RESULTS: The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000. DISCUSSION AND LIMITATIONS: Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions) instruments. IMPLICATIONS FOR HEALTH CARE PROVISION: Sleep disturbance is predictive of depression relapse, and is the most common residual symptom in patients who have been successfully treated with fluoxetine for depression. Thus, identifying cost-effective strategies for the treatment of insomnia symptoms is important for this patient population. IMPLICATIONS FOR HEALTH POLICIES: Treatment guidelines and drug coverage decisions should be based on clinical evidence, effectiveness, and economic criteria (i.e., whether an effective drug therapy produces sufficient benefits given its costs). This information about the overall value of eszopiclone can be measured as the cost per QALY gained with the use of ESZ+FLX compared with FLX alone. In order to make decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information. IMPLICATIONS FOR FURTHER RESEARCH: The residual efficacy observed in the clinical trial following the discontinuation of co-therapy should be explored further to determine whether intermittent treatment with ESZ+FLX is a cost-effective strategy. PMID- 20571181 TI - Impact of drug cost sharing on service use and adverse clinical outcomes in elderly receiving antidepressants. AB - BACKGROUND: Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. AIMS: To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. METHODS: Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. RESULTS: Neither policy affected the rates of visits to physicians or psychiatrists for depression, hospitalizations with a depression diagnosis, or long-term care admissions. DISCUSSION: The cost-sharing policies studied may have contained non-essential antidepressant use without substantially increasing mental health service utilization. However, it is possible that the policies had effects that we were unable to detect, such as increasing rates of visits to social workers or psychologists or forcing patients to reduce other spending. Further, the sequential implementation of the policy changes, makes it difficult to estimate the effect of a direct change from full coverage to a coinsurance/income-based deductible policy. IMPLICATIONS FOR HEALTH POLICIES: It may be possible to design policies to contain non-essential antidepressant use without substantially increasing other service utilization or adverse events. However, because undertreatment remains a serious problem among depressed elderly, well-designed prescription drug policies should be coupled with interventions to address under treatment. PMID- 20571182 TI - Hydrothermal synthesis and characterization of hydroxyapatite and fluorhydroxyapatite nano-size powders. AB - Pure hydroxyapatite (HAp) and fluoride-containing apatite powders (FHAp) were synthesized using a hydrothermal method. The powders were assessed by x-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscope (SEM) and F-selective electrode. X-ray diffraction results revealed the formation of single phase apatite structure for all the compositions synthesized in this work. However, the addition of a fluoride ion led to a systematic shift in the (3 0 0) peak of the XRD pattern as well as modifications in the FTIR spectra. It was found that the efficiency of fluoride ion incorporation decreased with the increase in the fluoride ion content. Fluorine incorporation efficiency was around 60% for most of the FHAp samples prepared in the current study. Smaller and less agglomerated particles were obtained by fluorine substitution. The bioactivity of the powder samples with different fluoride contents was compared by performing cell proliferation, alkaline phosphatase (ALP) and Alizarin red staining assays. Human osteoblast cells were used to assess the cellular responses to the powder samples in this study. Results demonstrated a strong dependence of different cell activities on the level of fluoridation. PMID- 20571185 TI - A novel technique for phase synchrony measurement from the complex motor imaginary potential of combined body and limb action. AB - In this study, we proposed and evaluated the use of the empirical mode decomposition (EMD) technique combined with phase synchronization analysis to investigate the human brain synchrony of the supplementary motor area (SMA) and primary motor area (M1) during complex motor imagination of combined body and limb action. We separated the EEG data of the SMA and M1 into intrinsic mode functions (IMFs) using the EMD method and determined the characteristic IMFs by power spectral density (PSD) analysis. Thereafter, the instantaneous phases of the characteristic IMFs were obtained by the Hilbert transformation, and the single-trial phase-locking value (PLV) features for brain synchrony measurement between the SMA and M1 were investigated separately. The classification performance suggests that the proposed approach is effective for phase synchronization analysis and is promising for the application of a brain-computer interface in motor nerve reconstruction of the lower limbs. PMID- 20571184 TI - Comparison of fractal dimension estimation algorithms for epileptic seizure onset detection. AB - Fractal dimension (FD) is a natural measure of the irregularity of a curve. In this study the performances of three waveform FD estimation algorithms (i.e. Katz's, Higuchi's and the k-nearest neighbour (k-NN) algorithm) were compared in terms of their ability to detect the onset of epileptic seizures in scalp electroencephalogram (EEG). The selection of parameters involved in FD estimation, evaluation of the accuracy of the different algorithms and assessment of their robustness in the presence of noise were performed based on synthetic signals of known FD. When applied to scalp EEG data, Katz's and Higuchi's algorithms were found to be incapable of producing consistent changes of a single type (either a drop or an increase) during seizures. On the other hand, the k-NN algorithm produced a drop, starting close to the seizure onset, in most seizures of all patients. The k-NN algorithm outperformed both Katz's and Higuchi's algorithms in terms of robustness in the presence of noise and seizure onset detection ability. The seizure detection methodology, based on the k-NN algorithm, yielded in the training data set a sensitivity of 100% with 10.10 s mean detection delay and a false positive rate of 0.27 h(-1), while the corresponding values in the testing data set were 100%, 8.82 s and 0.42 h(-1), respectively. The above detection results compare favourably to those of other seizure onset detection methodologies applied to scalp EEG in the literature. The methodology described, based on the k-NN algorithm, appears to be promising for the detection of the onset of epileptic seizures based on scalp EEG. PMID- 20571183 TI - Effects of magnesium alloys extracts on adult human bone marrow-derived stromal cell viability and osteogenic differentiation. AB - In this study, adult human bone marrow-derived stromal cells (hBMSCs) were cultured in extracts of magnesium (Mg) and the Mg alloys AZ91D and NZ30K for 12 days. We studied the indirect effects of Mg alloys on hBMSC viability. Alkaline phosphatase activity and the expression of osteogenic differentiation marker genes were used to evaluate the effects of the Mg alloys on the osteogenic differentiation of hBMSCs. The results indicate that or = 65 years) patients all with the same FH North Karelia mutation living in North Karelia (eastern Finland) was identified, 37 of whom (aged 65 to 84 years) agreed to participate. All but one of these FH patients had been using statins for approximately 15 years. Population-based controls (aged 65 to 84 years, n= 309) were the participants of the Health 2000 Survey living in eastern Finland. The cognitive assessment was conducted with tests for verbal fluency, Word List Learning (WLL) and Word List Delayed Recall (WLDR) subtests in the Consortium to Establish a Registry for Alzheimer's disease test battery. After adjustment for age, gender, education, diabetes mellitus, and coronary heart disease, FH patients were more likely to be in the top tertile of the WLDR (Odds ratio (OR) 3.40, 95% confidence interval (CI) 1.52-7.63) and WLL3 (OR 2.83, 95% CI 1.28-6.25) subtests. When the FH patients were subdivided according to the median length of their statin therapy, the ORs to be in the top tertile in the WLDR subtest were 1.65 (95% CI 0.52-5.25) for those with less and 5.40 (95% CI 1.74-17.72) in those individuals with more than median length of statin therapy. In conclusion, aged FH patients receiving long-term statin therapy exhibited better episodic memory than population controls, and this association became even more pronounced with longer statin therapy. PMID- 20571224 TI - Effect of mechanical ventilation on microvascular perfusion in critical care patients. AB - PURPOSE: Microvascular perfusion, pivotal for adequate tissue oxygenation is potentially linked to outcome in critical care therapy. Mechanical ventilation (MV) and positive end-expiratory pressure (PEEP) as standard concepts of respiratory management are known to have deleterious effects on regional organ perfusion especially in the splanchnic area. As these effects have been attributed to different physiologic mechanisms, the purpose of this study was to investigate the effect of positive pressure ventilation on extra-abdominal tissue perfusion in non-surgical intensive care patients. METHODS: Sublingual microcirculation was evaluated in 46 severely ill patients (group 1: n=26 requiring MV and PEEP; group 2: n=20 spontaneous breathing) admitted to the intensive care unit using sidestream darkfield intravitalmicroscopy. According to current guidelines, sublingual vessels were categorized by means of size and flow in semi-quantitative categories determining microvascular flow index (MFI). Total microvascular flow index (TMFI) was calculated for each patient as mean value of flow in all vessel categories. RESULTS: No significant difference was observed between both groups in microvascular flow index in each vessel category and in total microvascular flow index. Patients requiring mechanical ventilation presented with more comorbidities and higher acuity of illness scores resulting in a higher ICU mortality, which however was not accompanied by microcirculatory differences at the time of measurement. CONCLUSION: Mechanical ventilation and PEEP have no general deleterious effects on microvascular perfusion of the sublingual mucosa. However, further clinical studies are required to investigate potential effects of higher levels of ventilation pressure or PEEP on microvascular perfusion. PMID- 20571225 TI - Calcitonin gene-related peptide, substance P, nitric oxide and epinephrine modulate bone marrow micro circulation of the rabbit tibia and femur. AB - Different bones have different blood supplies, which may influence bone healing. Therefore, elucidation of the mechanisms involved in the regulation of bone marrow blood flow in different bones is of high clinical importance. To assess the micro circulation of bone marrow of the femur and tibia simultaneously, flow velocities were continuously measured by a two-channel laser-Doppler flowmeter. The probes were introduced into the femoral and tibial diaphysis, respectively, in the anesthetized rabbit. Changes in micro circulation of the bone marrow were elicited by intra-arterial bolus injections of vasoactive substances: epinephrine (E), calcitonine-gene related peptide (CGRP), substance P (SP), sodium nitroprusside (SNP), E and Ebrantil. Systemic arterial blood pressure was recorded with an electro-manometer. Micro vascular resistance (MVR) and 50% recovery time (50RT) to baseline flow level were calculated from the measured data. Flow velocity in the femur was significantly higher. Epinephrine considerably reduced micro vascular blood flow, which could be significantly warded off by Ebrantil. CGRP and SP did not change MVR. Application of SNP resulted in reduction of flow velocity, but it also decreased MVR. No statistically significant differences were found between reactions of the micro circulation in the two marrows. These results suggest that there are no significant differences between the blood flow response patterns of these two bone marrow sites, thus the regulation patterns of the micro circulation of the two bones are also similar. PMID- 20571226 TI - Comparison of time-resolved CT-angiography, contrast-enhanced ultrasound and digital subtraction angiography in a patient with a small type II endoleak after endovascular aneurysm repair. AB - We report discordant imaging findings of a small persistent type II endoleak in a 72-year-old man who had undergone endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm. Although the aneurysm was growing in size digital subtraction angiography could not detect an endoleak, but time-resolved CT angiography and contrast enhanced ultrasound did detect a small type II endoleak. PMID- 20571227 TI - Erythrocyte deformability in macrocytosis determined by means of ektacytometry techniques. AB - There is little information regarding the behaviour of red blood cell deformability in macrocytosis. We have determined in 114 patients with macrocytosis (MCV > 97 fL) and in 115 age and sex-matched subjects with normocytosis (VCM < 97 fL) erythrocyte deformability by means of ektacytometric techniques (Rheodyn SSD) measuring the erythrocyte elongation index (EEI) at 12, 30 and 60 Pa. Patients with macrocytosis showed statistically higher EEI at all the shear stresses tested when compared with controls (p < 0.001). When patients with macrocytosis were classified according to their main diagnosis as hepatic or renal disease, HIV and miscellaneous, 66.7%, 41.7%, 36.7% and 33.3% of patients, respectively, showed a EEI 60 higher than 61.8% (mean value of the control group + 2 SD). Linear regression analysis demonstrates that MCV, bilirubin, triglycerides and alanine aminotransferase were the main variables influencing EEI 60. An increased surface/volume ratio of the red blood cells may be the main cause related with a higher erythrocyte deformability in a relevant percentage of macrocytosis. Further research is required to confirm our findings by designing case-control pathology-specific studies. PMID- 20571228 TI - Interrelationships between lipid peroxidation and total antioxidant status in sedentary controls and unprofessional athletes. AB - We examined the thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation, and the total antioxidant status (TAS) in 81 unprofessional athletes subdivided into three subgroups. The first group included 28 subjects who practised endurance sports, the second included 30 subjects who practised mixed sports, the third included 23 subjects who practised power sports. We enrolled also a group of 61 sedentary controls (SC). TBARS were increased and TAS was decreased in the whole group of athletes in comparison with SC; an almost similar behaviour was present also subdividing athletes according to the practised sport. A significant negative correlation between these two parameters emerged in SC but not in the whole group of athletes. Unless for the athletes that practised endurance sports a similar trend was found in athletes that practised mixed and power sports. In conclusion, at rest the symmetrical behaviour between the lipid peroxidation increase and the TAS decrease, observed in sedentary controls, was not evident in unprofessional athletes who practised different sports. PMID- 20571229 TI - Red blood cell deformability and aggregation, cell adhesion molecules, oxidative stress and nitric oxide markers after a short term, submaximal, exercise in sickle cell trait carriers. AB - The present study investigated the hemorheological and endothelial alterations in sickle cell trait (SCT) carriers in response to a submaximal exercise. Eleven SCT carriers and 11 subjects with normal hemoglobin performed submaximal exercise for 15 min. Blood was sampled at rest, at the end of exercise, and at 2 and 24 h of recovery. Hemorheological alterations observed in the SCT group were as follows: 1) lower RBC deformability at high shear stress at all time-points, with no relation to oxidative stress, 2) higher disaggregation threshold at all time points, suggesting RBC hyper-aggregation, and 3) higher blood viscosity at the end of exercise and during recovery. Exercise had a specific influence on the levels of the soluble cell adhesion molecules P and L-selectin in the SCT carriers, with higher P-selectin levels at all time-points and a greater increase in L-selectin levels during recovery. SCT carriers had slightly decreased nitrite levels at 24h of recovery, which might be clinically insignificant. In conclusion, the hemorheological alterations in association with lower NO production found in the SCT carriers are probably not sufficient to explain the medical complications sometimes reported in SCT carriers after exercise. PMID- 20571230 TI - Slow flow of passive neutrophils and sequestered nucleus into micropipette. AB - In the present study, the role of the nucleus and its contribution to the deformability of the passive neutrophils was investigated. To determine the rheological properties of the nucleus and of the neutrophil itself, deformation tests on single neutrophil and sequestered nucleus have been performed by micropipette under low aspiration pressure (80 Pa = 2-3 Pcr). The stiffness of the nucleus was found to be larger than that of the neutrophil, and its viscosity was found almost ten-fold higher. A subpopulation of neutrophils (Sub-A) showed two phases of deformation, a first rapid phase and a second phase with a constant deformation rate up to their full entrance, with an apparent viscosity mu app second-Phase(N Sub-A) = 286 +/- 123 Pa x s, calculated by the liquid drop model. Another subpopulation (Sub-B) of the tested neutrophils displayed three deformation phases: a first one reflecting the rapid entry of cell into the micropipette, a second with constant deformation rate, and a third phase, with a slower, also constant, deformation rate were recorded. The corresponding apparent viscosities were found as mu app-second-Phase(N Sub-B) = 341 +/- 94 Pa x s and mu app-third-Phase(N Sub-B) = 1651 +/- 734 Pa x s. The apparent viscosity values of the neutrophilic nucleus, mu app (N nucl) = 2468 +/- 1345 Pa x s and of the whole neutrophil calculated in the third phase of deformation, mu app-third-Phase(N Sub B) = 1651 +/- 734 Pa.s were comparable. These results support our hypothesis that the nucleus plays a significant role in the mechanical and rheological behavior of the neutrophil, especially when it has to pass through openings much smaller than its size. PMID- 20571231 TI - Mean platelet volume in patients with prehypertension and hypertension. AB - Patients with hypertension have evidence of platelet activation. Mean platelet volume (MPV), an indicator of platelet activation has been shown to be elevated in patients with hypertension. Prehypertension is also associated with an increase in cardiovascular morbidity and mortality. The aim of this study was to assess the MPV in patients with prehypertension and hypertension. This study included newly diagnosed and untreated 87 prehypertensive patients, 30 hypertensive patients and 35 normotensive control subjects matched for age, gender, and body mass index. All patients and controls gave informed consent. The MPV values of patients with prehypertension and hypertension were significantly higher than those of the control group (8.4 +/- 0.8 and 8.8 +/- 0.7 versus 7.9 +/ 0.5 fl; p < 0.05 and p < 0.001 respectively). It was also higher in hypertensives than in prehypertensives (8.8 +/- 0.7 versus 8.4 +/- 0.8 fl; p < 0.05). However, we found that the presence of the hypertension (beta = 0.28, P = 0.003) was only significant predictors of higher MPV in a multivariable model that adjusted for other variables. We have shown that, MPV, an indicator of platelet activation was significantly higher in patients with prehypertension and hypertension when compared with control subjects. We have also showed that MPV was also higher in patients with hypertension than in patients with prehypertension. However, presence of the hypertension was only significant predictor of higher MPV. PMID- 20571232 TI - Prognostic significance of serum Her2/neu, BCL2, CA15-3 and CEA in breast cancer patients: a short follow-up. AB - Breast cancer is the most common malignancy in women, options for treatment of breast cancers are complex and varied, there is a need for biological prognostic indicators that would, alone or in combination with others, be sufficient to predict disease recurrence and hence, the basis for supplemental treatment after local therapy. The aim of this study was to determine prognostic significance of serum Her2/neu, BCL2, CA 15-3 and CEA during the follow-up of the patients with breast cancer, also, to investigate the association between these biomarkers and clinicopathological parameters and patient outcomes in breast cancer. PATIENTS AND METHODS: Eighty nine patients with breast cancer stage I and II are enrolled in our study. Their age ranged from 35-59 years. Patients underwent radical mastectomy or breast-conserving surgery with axillary lymph node dissection. After the surgical treatment they had supplementary therapy. The size of the tumor was < 2 cm in 35 patients and > 2 cm in 54 patients. Their histological type was invasive duct carcinoma, 49 patients had lymph node positive and 40 had negative lymph node. Nine patients had recurrence of the disease during the 18 months of follow up. BCL2, Her2/neu, CEA and CA15-3 in sera had been monitored by ELISA before and after operation, every 6 months and at the time of diagnosis of first recurrence for 18 months. RESULTS: Preoperative serum levels of Her2/neu, BCL2, CA15-3 and CEA were significantly higher compared with the levels of the control group, these markers dropped significantly after operation. Univariate analysis of parameters associated with relapse showed that the clinicopathological factors (histologic grade, tumor stage and lymph nodes) and serum markers (HER2/neu, BCL2, CA15-3 and CEA) were significantly associated with recurrence of disease. Multivariate analysis of investigated parameters revealed that tumor stage, lymph nodes and serum tumor markers were significant variables predicting recurrence of tumor. CONCLUSION: Serum Her2/neu, BCL2, CA15-3 and CEA in breast cancer patients were useful markers for predicting aggressive behavior of tumor and elevated serum levels are associated with breast cancer relapse. Our relatively small study population limits the predictive power of the panels presented here, but the benefits of a serum biomarker and multimarker approach are clearly illustrated and further studies utilizing larger clinical cohorts are well warranted. PMID- 20571233 TI - Serum peptide/protein profiling by mass spectrometry provides diagnostic information independently of CA125 in women with an ovarian tumor. AB - In the present study, the use of a robust and sensitive mass spectrometry based protein profiling analysis was tested as diagnostic tools for women with an ovarian tumor. The potential additional diagnostic value of serum protein profiles independent of the information provided by CA125 were also investigated. Protein profiles of 113 serum samples from women with an ovarian tumor (54 malign and 59 benign) were generated using MALDI-TOF MS. A total of 98 peaks with a significant difference (p< 0.01) in intensity between women with benign tumors/cysts and malignant ovarian tumors were identified. After average linkage clustering, a profile of 46 statistical significant mass peaks was identified to distinguish malignant tumors and benign tumors/cysts. In the subgroup of women with normal CA125 values (< or =35 U/mL) (62 patients) 36 of the 504 mass peaks showed significant (p< 0.05) differences in intensity between benign and malignant disease. After average linkage clustering, 25 statistical significant mass values were identified in this clinical difficult and important subgroup presenting with normal CA125 values. The current study demonstrates the potential of mass spectrometry based serum protein profiling as a diagnostic tool in discrimination between benign ovarian tumors/cysts and malignant ovarian tumors. Additionally, the method provided diagnostic information independent of CA125. PMID- 20571234 TI - Thymidylate synthase gene polymorphisms effecting 5-FU response in breast cancer patients. AB - Our study supports the Drug-Gene Interaction principle, where patients experience adverse drug reactions (ADRs) due to genetic predisposition or due to single nucleotide polymorphisms (SNPs) in drug metabolizing genes. The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism. We determined the frequencies of polymorphisms in drug metabolizing enzyme like TYMS and correlated the drug response in 140 breast cancer patients compared to 150 controls, using PCR and RFLP method. In our results the TYMS1494del polymorphism was statistically significant; allele frequencies for 6bp deletion and 6bp insertion were 0.85 and 0.15 in BC (Breast Cancer) patients compared with 0.95 and 0.04 in controls. The enhancer region 2R/3R heterozygote genotypes were found to be not significant for BC risk. In this study combined genotypes showed 2 fold increased risk of BC. Frequency distribution of 2R and 3R allele among BC patients was 0.85 and 0.15 and 0.95 and 0.04 in controls respectively. Correlation analysis of TYMS enhancer region polymorphisms with drug response suggested that the response was poor in BC patients with 2R/3R and 2R/2R genotypes, but patients with poor response were fewer in number, that this gene may be important in drug response. Genetic screening of the drug metabolizing enzyme like TYMS for the presence of polymorphisms in breast cancer patients will become increasingly useful in individualizing drug therapy. PMID- 20571236 TI - Serum interleukin-8 and insulin like growth factor-1 in Egyptian bladder cancer patients. AB - BACKGROUND: Bladder cancer is a major health problem in Egypt as it represents the most common malignancy. AIM: Evaluation of the potential usefulness of serum IL-8 and IGF-1 in Egyptian bladder cancer patients. METHODS: Serum levels of IL-8 and IGF-1 were determined in 51 bladder cancer patients and 45 controls using a chemiluminescence enzyme immunometric assay. RESULTS: Serum IL-8 was significantly higher in cancer patients than in controls (P < 0.0001). It was significantly higher in patients with invasive cancer than those with superficial cancer (P < 0.01). Also, IL-8 showed a significant elevation in relation to schistosomal infection (P = 0.02) however, it did not differ in relation to either pathological type of tumor or its grade (P > 0.05). Receiver operating characteristic (ROC) curve indicated that IL-8 cut-off value of 35 pg/mL yielded the best combination of sensitivity (71%) and specificity (98%) for differentiating patients with bladder cancer from control subjects. Serum IGF-1 levels showed no significant difference between bladder cancer patients and controls (P > 0.05). There was no relationship between IGF-1 levels and clinicopathological parameters. CONCLUSIONS: In Egyptian patients with bladder cancer, serum IL-8 is significantly elevated and its level is related to tumor invasion and associated schistosomal infection. Moreover, serum IGF-1 level does not help as a serum tumor marker in these patients. PMID- 20571235 TI - Breast cancer: interaction between oxidant-antioxidant dynamics and inflammation in Indian females. AB - OBJECTIVES: Oxidative stress and pro-inflammatory mediators have been implicated in breast carcinogenesis. We attempted to evaluate the markers of oxidative stress, antioxidant mechanism and the inflammatory pathway in patients with breast cancer. METHODS: This study was carried out in departments of Biochemistry and Surgery, Maulana Azad Medical College and associated Hospitals, New Delhi, India. A total of 60 cases of carcinoma of the breast and 60 healthy controls were included in the study. The parameters that were assayed include markers of oxidative stress-conjugated dienes, thiobarbitone reactive substances (TBARS), antioxidants-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and markers of inflammation-interleukin-6(IL-6) and ferritin. RESULTS: There was a significant decline in the antioxidant levels and a significant rise in oxidant levels in patients with carcinoma of the breast, compared to controls. The inflammatory markers-IL-6 and ferritin-were also significantly higher in patients with breast cancer. A significantly positive correlation was observed between the IL-6 levels and conjugated dienes with the stage of breast carcinoma; whilst a significantly negative correlation was observed between the levels of conjugated dienes and superoxide dismutase and superoxide dismutase levels with the disease staging. CONCLUSIONS: This study underlines the interplay between inflammatory pathways and oxidative stress in the pathogenesis of breast cancer. MINI ABSTRACT: An intense research is underway to identify the possible risk factors and the molecular mechanisms involved in pathogenesis of breast cancer. Inflammation and oxidative stress are two such etiologies investigated in our study. PMID- 20571238 TI - Prediction of hematocrit and red cell deformability with whole body biological impedance. AB - Bioelectrical impedancemetry has been used to evaluate hemorheological parameters in vitro but whole body impedance measurements are also correlated to some hemorheologic factors, due to their close relationship with determinants of electric properties of blood. In previous studies, we have determined a set of predictive equations for hematocrit, whole blood viscosity and plasma viscosity in both sedentary and trained individuals. In this study we aimed at verifying those findings and investigating for other equations in a sample of 62 subjects whose body composition was assessed with a multifrequency bioelectrical impedancemeter using low intensity at the following frequencies: 1, 5, 10, 50 and 100kHz. Viscometric measurements were done with a falling ball viscometer. Hematocrit was measured with microcentrifuge. We confirm that hematocrit was correlated with impedance measurements at 50 kHz (r=-0.671, p < 0.01), and describe a new predictive equation for RBC rigidity index "k" calculated with the equation of Quemada, ("k" index = 0.0003 Z50 + 1.2815; mean difference: -0.0506; 95% confidence interval of -0.0134 to 0.00324) that is also correlated with impedance measurements at 50 kHz (r = 0.526, p < 0.01). Although the precision of these formulae is not sufficient for allowing true "predictions" of hematocrit and red cell deformability, these findings confirm that factors of viscosity are to some extent reflected by whole body electric properties. PMID- 20571237 TI - Positive identification of CA215 pan cancer biomarker from serum specimens of cancer patients. AB - BACKGROUND: To evaluate the clinical utility of CA215 as a pan cancer biomarker, serum levels of CA215 were determined with clinically defined serum specimens from over 500 cancer patients and compared with results obtained by other nine established cancer markers. The molecular nature of this cancer-associated antigen from selected patients' sera was determined. METHODS: By using improved immunoassays, serum levels of CA215 and other known biomarkers were determined for respective positive detection rates. The molecular size of CA215 from cancer patients was determined by Western blot assay. RESULTS: By using 0.1 AU/ml as the normal cut-off value, the positive rates of CA215 for different cancers were shown to be 52% (lung), 74% (liver), 44% (colon), 61% (esophagus), 60% (stomach), 59% (ovary), 40% (prostate), 71% (breast), 38% (kidney), 41% (pancreas), 51% (cervix), and 83% (lymphoma), respectively. Other cancer markers including AFP, CEA, CA125, CA19-9, CA15-3, Cyfra21-1, Ferritin, beta(2) microglobulin and PSA were also parallelly compared. A combination of CA215 with other tissue associated cancer markers generally resulted in much higher cancer detection rates. CA215 detected from cancer patients was confirmed to be human immunoglobulins that contain common RP215-specific carbohydrate-associated epitope. CONCLUSION: Through clinical evaluations of serum specimens of various cancer patients, CA215 was confirmed to be human cancer cell-derived immunoglobulins. CA215 is apparently comparable to or better than other known biomarkers for the positive detection and monitoring of many types of human cancers. PMID- 20571239 TI - The effect of salvianolic acid B combined with laminar shear stress on TNF-alpha stimulated adhesion molecule expression in human aortic endothelial cells. AB - The study was conducted to investigate the effect of Salvianolic acid B (Sal B) on TNF-alpha-stimulated adhesion molecule expression i.e. vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human aortic endothelial cells (HAECs) under laminar shear stress (LSS) condition. Exposure of HAECs to LSS (12 dynes/cm(2) for 6 h decreased the TNF alpha-induced protein expression of adhesion molecules i.e. VCAM-1, ICAM-1 and E selectin. Pre-treatment of HAECs with Sal B (10 microg/ml) then exposed to LSS (12 dynes/cm(2)) for 6 h significantly inhibited VCAM-1, ICAM-1 and E-selectin expression stimulated by TNF-alpha. Moreover, combined Sal B and LSS treatment inhibited the adhesiveness of monocytic U937 cells to TNF-alpha-stimulated HAECs. We further examined the molecular mechanisms and found that the combination of Sal B and LSS treatment dramatically inhibited TNF-alpha-induced NF-kappaB activation evidenced by IkappaBalpha degradation and p65 nuclear translocation in HAECs. This study provides the first biomechanopharmacological evidence that Sal B has a combination effect with LSS to reduce the expression of three adhesion molecules, leading to reduced monocyte adhesion to HAECs, at least in part, by inhibiting the NF-kappaB signaling pathway. Data from this study thus support the potential clinical application of Sal B in vascular inflammatory diseases. PMID- 20571240 TI - Sex-dependent differences in rheological properties and the relation of blood viscosity to erythrocyte aggregation indices among morbidly obese patients. AB - Some studies indicate that obesity is associated with rheological disturbances. Because there are usually sex differences in the type of obesity we decided to evaluate rheological differences between male and female obese patients. We studied 18 morbidly obese men, mean age 43.66 +/- 11.32 years, mean body mass index (BMI) 49.82 +/- 6.03 kg/m2 and 20 obese females, mean age 40.6 +/- 11.86 years, mean BMI 47.41 +/- 8.81 kg/m2. Blood and plasma viscosity measurements were performed using a cone-plate viscometer (Brookfield DV-II). Erythrocyte elongation and red blood cell (RBC) aggregation were measured using the Laser assisted Optical Rotational Cell Analyser (LORCA). Whole blood viscosity and RBC deformability expressed by the elongation index were significantly higher in obese men. We did not observe differences in plasma viscosity, corrected blood viscosity and aggregation parameters among the obese population. Blood viscosity correlated with selected RBC aggregation indices. We conclude that morbidly obese patients presented sex-dependent differences in some rheological properties. This study indicates a relation between erythrocyte aggregation indices and blood viscosity in obese populations. PMID- 20571241 TI - Blood lactate and pyruvate levels in the perioperative period of liver resection with Pringle maneuver. AB - INTRODUCTION: Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery, portal vein, and bile duct. This study aimed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection. METHODS: Twenty five consecutive patients undergoing elective liver resection were prospectively randomized either to be treated with the Pringle maneuver (Pringle group, n = 14) or without clamping (Controls, n = 11). Blood lactate levels, pyruvate levels, and hepatic vein oxygen saturation were monitored perioperatively. RESULTS: Patients were comparable with respect to resection time, intraoperative blood loss, and duration of surgery. The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls (2.6 +/- 0.3 vs 1.8 +/- 0.2 mmol/l; p < 0.05). Further, the Pringle maneuver significantly increased hepatic venous lactate (3.3 +/- 0.3 vs 1.6 +/- 0.3 mmol/l; p < 0.05) and lactate/pyruvate ratio in hepatic venous blood (43 +/- 8 vs 21 +/- 5; p < 0.05) during surgery. This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group (61 +/- 4 vs 73 +/- 4%; p < 0.05). CONCLUSION: Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus. Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection. PMID- 20571242 TI - Behaviour of nitric oxide metabolites in unprofessional athletes before and after a cardiopulmonary test. PMID- 20571243 TI - No apparent correlation between Behcet's disease and oxidative stress disturbance. AB - Behcet's disease (BD) is a chronic, progressive and inflammatory multisystemic disease, that significantly affects the cardiovascular system. Oxidative stress (OS) is a disturbance in oxidant/antioxidant balance in favor of oxidants. The OS that increases acutely and chronically due to the inflammatory process plays an important role in the pathogenesis of the cardiovascular system effects of the disease by causing endothelial dysfunction in vascular structures. The aim of our study was to investigate the relationship between OS and myocardial perfusion, which is based on microvascular dysfunction, in BD. MATERIAL AND METHOD: Twenty seven patients with BD (16 M, 11 F, mean age: 38.7 +/- 9.4 years) and 22 healthy volunteers (12 M, 10 F, mean age: 35.8 +/- 6.5 years) participated in our study. Technetium-99m methoxyisobutylisonitrile single photon emission computed tomography (Tc-99m MIBI SPECT) stress-rest test was performed with two-day protocol. Myocardial perfusion scores (summed stress score, summed rest score, summed difference score, fix defect score) and perfusion defect prevalence (stress, rest, ischemic and fixed) were determined as the percentage of left ventricle. Coronary angiography was performed in patients with abnormal myocardial perfusion scintigraphy. For OS analysis, the blood samples were taken immediately before the first imaging procedure and were studied for malondialdehyde, glutathione, nitrite, nitrate, vitamin C, retinol, and carotene. RESULTS: In the BD group, a total of 9 patients had abnormal findings in their stress and rest electrocardiography. Perfusion defect in myocardial perfusion scintigraphy was observed in 14 patients (51.8%). Twelve patients accepted coronary angiography, and their results were normal. In the comparison of myocardial perfusion scores, perfusion defect prevalence and OS parameters, there was a significant difference between the BD and control groups. In the BD group, no correlation was observed between myocardial perfusion scores, perfusion defect prevalence and OS parameters. CONCLUSION: Defects in myocardial perfusion and increase in OS were observed in BD; however, there was no correlation between the two findings in the inactive period. In other words, the prevalence and intensity of myocardial perfusion defects can vary at different OS levels. PMID- 20571244 TI - Estimation of vessel age and early diagnose of atherosclerosis in progeria syndrome by using echo-tracking. AB - The stiffness of the arteries normally increases with age. Radiofrequency echo tracking is a non-invasive ultrasound method which is able to detect the stiffness of the arteries, represented by the beta stiffness index. The estimation of biological age of vessels is possible on the basis of the normal age-group specific beta stiffness values. The beta stiffness index becomes higher in early stages of atherosclerosis as well, before any visible morphological changes. Hutchinson-Gilford progeria syndrome (HGPS) is rare genetic disorder resulting in accelerated aging including appearance of progressive atherosclerosis at an early age which determines the quality and term of life of these patients. Determination of vascular age and early diagnosis of atherosclerosis seems crucial. According to our knowledge, the estimation of vascular age detected with radiofrequency echo-tracking in HGPS patients, in contrast to the normal age-specific beta stiffness values, has not been published yet. PMID- 20571245 TI - Improved viscosity modeling in patients with type 2 diabetes mellitus by accounting for enhanced red blood cell aggregation tendency. AB - AIMS: Distorted wall shear stress (WSS) in patients with type 2 diabetes mellitus (T2DM) may be partly explained by an altered red blood cell aggregation tendency (RAT) on viscosity at low shear rate (SR). The present study evaluates viscosity modeling by implementation of hematocrit and RAT in patients with and without T2DM (non-T2DM). METHODS: A Couette viscometer and LORCA aggregometer provided viscosity and RAT on 6 shear rates in 55 patients (46-78 yrs, 66% male, T2DM: n = 28), following informed consent. Using a K-fold cross-validation, two linear mixed models predicted by SR and Hct and by SR, Hct and RAT were compared. RESULTS: In non-T2DM modeling was improved in relatively low RATs (48%, p = 1.0 x 10-11) and became worse in relatively high RATs (-18%, p = 0.019). In T2DM the opposite was observed, as modeling became worse in relatively low RATs (-16%, p = 0.001) but was improved in relatively high RATs (22%, p = 0.022). CONCLUSIONS: In addition to confirming previous research, major differences in modeling improvement between T2DM and non-T2DM were found. Especially patients with T2DM, a high RAT and often high viscosity at low SR benefit from a more accurate viscosity modeling. Further studies should evaluate how these findings affect WSS in these patients. PMID- 20571246 TI - Prognostic value of post-ischemic stunning as assessed by gated myocardial perfusion single-photon emission computed tomography: a subanalysis of the J ACCESS study . AB - BACKGROUND: To determine the prognostic value of post-ischemic stunning, the Japanese assessment of cardiac event and survival study by quantitative gated myocardial single-photon emission computed tomography (SPECT) (J-ACCESS) study was reevaluated. METHODS AND RESULTS: Of the 4,031 patients of the J-ACCESS, the present study evaluated 1,089 who completed gated SPECT both after stress and at rest. To assess post-ischemic stunning, the following measurements (left ventricular volumes after stress minus volumes at rest) were made: Deltaend systolic volume (DeltaESV), Deltaenddiastolic volume (DeltaEDV) and Deltaejection fraction (DeltaEF). Myocardial stunning defined either as DeltaESV >or=5 ml, DeltaEDV >or=5 ml or DeltaEF or=5 ml or DeltaEDV >or=5 ml than in those without, whereas DeltaEF or=5 ml was also an independent parameter, in addition to LVEF = 1.0). Seven possible histopathologic indicators of resistance to insertion of the electrode due to contact with the basilar membrane, osseous spiral lamina and/or spiral ligament were evaluated by analysis of serial sections from the temporal bones along the course of the electrode tracks. RESULTS: Obvious obstruction by abnormal intracochlear bone or soft tissue accounted for only 6 (22%) of the 27 partial insertions. Of the remaining 21 bones with incomplete insertions and 13 bones with complete insertions, dissection of the spiral ligament to the lateral cochlear wall was the only histopathologic indicator of insertion resistance identified with significantly higher frequency in the partial-insertion bones than in the complete-insertion bones (p = 0.003). An observed trend for the percentage of complete insertions to decrease with the number of times the electrode penetrated the basilar membrane did not reach significance. In the bones without an obvious obstruction, the most frequently observed indicator of insertion resistance was dissection of the spiral ligament (with no contact of the lateral cochlear wall) identified in 67% (14/21) of partial-insertion bones and in 92% (12/13) of complete-insertion bones. CONCLUSION: These results are consistent with the view that (1) electrode contact with cochlear structures resulting in observable trauma to the basilar membrane, osseous spiral lamina and/or spiral ligament does not necessarily impact the likelihood of complete insertion of the electrode array and (2) once contact trauma to the spiral ligament reaches the point of dissection to the cochlear wall, the likelihood of incomplete insertion increases dramatically. PMID- 20571259 TI - Sensitivity of bimodal listeners to interaural time differences with modulated single- and multiple-channel stimuli. AB - In a previous study, it was shown that users of a cochlear implant and a contralateral hearing aid are sensitive to interaural time differences (ITDs). In the current study, we investigated (1) the influence on ITD sensitivity of bilaterally varying the place of excitation in the cochlea and of modulation frequency, and (2) the sensitivity to ITD with a 3-channel stimulus generated using continuous-interleaved-sampling (CIS)-like processing. The stimuli were (1) a high-frequency carrier (acoustic sinusoid and single-electrode electric pulse train), modulated with a half-wave-rectified low-frequency sinusoid (a so-called transposed stimulus), and (2) a 3-channel stimulus, generated by sending an acoustic click train through processing similar to the CIS strategy. Four bimodal listeners were sensitive to ITD for both stimulus types. For the first stimulus type, there was no significant influence on ITD sensitivity of the acoustic carrier frequency. Performance decreased with increasing modulation frequency with a limit of sensitivity at around 150-200 Hz. Sensitivity was similar for the single- and 3-channel stimulus. The results indicate the possibility of ITD perception with adapted clinical processors, which can lead to improved sound source localization and binaural unmasking. PMID- 20571260 TI - Perforated peptic ulcer disease: a review of history and treatment. AB - BACKGROUND: In the last one hundred years much has been written on peptic ulcer disease and the treatment options for one of its most common complications: perforation. The reason for reviewing the literature was evaluating most common ideas on how to treat perforated peptic ulcers (PPU) in general, opinions on conservative treatment and surgical treatment and summarizing ideas about necessary pre-, per- and postoperative proceedings. METHOD: All relevant articles found by Medline, Ovid and PubMed search were used. RESULTS: A hundred articles written between 1929 and 2009 were reviewed. Of these, 9 were about the history of treatment, 7 about conservative treatment, and 26 were about the surgical procedure of which 8 were addressing laparoscopic correction. Overall there is no consensus, but some advice is given. For conservative treatment there are only a few indications. Use of an omental patch is recommended, irrigation and drainage are not. Laparoscopic correction of PPU as well as for definitive ulcer surgery has many advantages. CONCLUSIONS: Surgery for PPU is still a subject of debate despite more than an era of published expertise, indicating the need for establishing guidelines. PMID- 20571261 TI - Reverse double-stapling end-to-end esophagogastrostomy in proximal gastrectomy. AB - BACKGROUND: Proximal gastrectomy is a surgical option for proximally located early gastric cancer. We present a new double-stapling method for proximal gastrectomy and esophagogastrostomy. METHODS: We examined the safety of proximal gastrectomy by analyzing the lymph node metastasis rate in 53 patients who underwent total gastrectomy due to proximally located early gastric cancer from January 2004 to December 2008. We applied the double-stapling method used in distal gastrectomy reversely to proximal gastrectomy and esophagogastrostomy in 15 patients. RESULTS: Retrospective analysis showed that proximal early gastric cancer metastasizes to only lymph node station 2, 3 and 7 which were completely removed during proximal gastrectomy. Fifteen patients underwent proximal gastrectomy using a new method which left no gastrostomy wound for the insertion of a circular stapler in the remaining stomach. The median operation time was 156.5 min and median postoperative hospital stay was 8.0 days. There were only 2 cases of wound complications during hospital stay. Two cases of anastomosis site strictures which developed after discharge were successfully treated with balloon dilatation. CONCLUSION: We presented a new 'reverse double-stapling method' for proximal gastrectomy, which seems to be a fast and feasible method that leaves no gastrostomy wound in the remaining stomach. PMID- 20571262 TI - The vascular stapler in uncinate process division during pancreaticoduodenectomy: technical considerations and results. AB - BACKGROUND: Few studies describing the use of stapling devices for uncinate process division during pancreaticoduodenectomy (PD) have data regarding outcomes. Our aim is to discuss our technique and the peri-operative outcomes with the use of the linear vascular stapler for division of the uncinate process during PD. MATERIALS AND METHODS: 19 consecutive patients who underwent stapler division of the uncinate process ('stapler' group) were compared to 20 consecutive patients operated without stapler ('no-stapler' group). RESULTS: The overall surgical morbidity in the no-stapler group was 25% (5/20) and 31.6% (6/19) in the stapler group (p = 0.731). The mean blood loss in the no-stapler group was 1,077.5 +/- 594 ml compared to 778 +/- 302 ml in the stapler group (p = 0.113). The mean operative duration was 498 +/- 105 min in the no-stapler group and 490 +/- 60 min in the stapler group (p = 0.773). The average number of lymph nodes retrieved was 6.1 +/- 3 in the no-stapler group versus 5.9 +/- 4 in the stapler group (p = 0.627). Neither group had positive resection margins. CONCLUSION: Stapler division of the uncinate process for selected periampullary tumours compares well with the conventional method, has comparable peri-operative outcomes without compromising oncological radicality and has the potential to simplify uncinate resection. PMID- 20571263 TI - Accurate staging, selective preoperative therapy and optimal surgery can deliver a good oncological and functional outcome in low rectal cancer. PMID- 20571264 TI - Distal margins in radical resections for rectal cancer after chemoradiation therapy: how short is long enough? AB - BACKGROUND: The purpose of our study was to assess the impact of distal margin length on outcome in patients with rectal cancer treated with neoadjuvant chemoradiation therapy (CRT) followed by radical resection. METHODS: Fifty-three consecutive patients were evaluated. The selection criteria included: adenocarcinoma of the mid- or distal rectum, locally advanced stage, absence of distant metastases, and preoperative CRT followed by proctectomy with total mesorectal excision. The operations included low anterior resection in 33 patients (62%) and abdominoperineal resection in 20 (38%). The outcome measures were: tumor regression, complete pathologic response, length of distal resection margins, status of radial margins and recurrence rate. RESULTS: Forty-eight patients (91%) had tumor regression, and 11 (21%) had a complete pathologic response. Distal resection margins were tumor-free in all patients, ranging in length from 0.1 to 7.4 cm (mean = 2.2). Follow-up (mean = 48.8 months) was current in 50 of 53 patients (94%). There was no locoregional recurrence. CONCLUSIONS: Distal resection margins shorter than 1-2 cm appear to be equivalent to longer margins in patients who undergo CRT followed by proctectomy with total mesorectal excision. These findings may lead to greater utilization of sphincter saving procedures in rectal cancer. PMID- 20571265 TI - Spectrum of disease and outcome among patients with acute diverticulitis. AB - BACKGROUND: This study was designed to evaluate the natural history of patients admitted for acute diverticulitis. METHODS: Nine hundred and seventy-seven patients admitted to Oulu University Hospital for acute symptoms of diverticular disease during the 20-year period from 1986 to 2005 were identified using a database. RESULTS: Six hundred and ninety-five patients were admitted for uncomplicated diverticulitis and 282 for complicated diverticulitis. The patients admitted for uncomplicated diverticulitis were younger than the others and 66% of them were admitted only once. The number of admissions preceding perforation was higher in the 1980s, and the number of admissions was unrelated to the degree of perforation or the outcome of the patients. The annual prevalence of sigmoid diverticular perforation increased from 2.6/100,000 in 1986 to 4.2/100,000 in 2005. Seventy (10%) of the 695 patients admitted for the first time for acute diverticulitis underwent urgent surgery during the same admission and 66 (9%) had elective surgery during a later admission. Overall hospital mortality was 2.3%, being 1% among those admitted for acute diverticulitis and 5.5% among those admitted for diverticular perforation. Two hundred and thirty-four (42%) of the 555 nonoperated patients with acute diverticulitis developed a recurrent episode of diverticulitis. The course of recurrent disease was similar to the primary episode. CONCLUSION: Two or more preceding admissions for acute diverticulitis do not warrant sigmoid resection after diverticulitis. Young patients do not have a greater risk of complicated diverticulitis than older ones. PMID- 20571266 TI - Surgical treatment of pancreatic neuroendocrine tumors: report of 112 cases. AB - OBJECTIVES: To review the clinical data of a group of patients with pancreatic neuroendocrine tumors (pNETs) and to investigate the role of surgery in the treatment for pNETs by analyzing clinical manifestations and postoperative course of this rare disease. METHODS: A total of 112 patients (aged 21-76 years; 45 males) who underwent treatment between 1980 and 2003 were recruited in this study. Patients' data related to demographics and characteristics, diagnostic studies, surgical and tumor characteristics and survival were retrospectively reviewed. RESULTS: Forty-six patients (41.1%) had a well-differentiated neuroendocrine tumor (WDT), 44 (48.2%) a well-differentiated neuroendocrine carcinoma (WD-Ca) and 12 (10.7%) a poorly differentiated neuroendocrine carcinoma (PD-Ca). Nonfunctional tumors were seen in 65 (58.0%) patients, whereas functional tumors were found in 47 (42.0%) patients, including 26 insulinomas, 17 gastrinomas, 2 VIPomas, 1 glucagonoma, and 1 ACTHoma. The sensitivity of computed tomography was 87.1%. Surgical resection was performed in 99 (88.4%) patients. Thirty-eight (33.9%) patients underwent partial pancreaticoduodenectomy, 32 (28.6%) had distal pancreatectomy and 29 (25.9%) underwent enucleation. No surgery-related death occurred. The common postoperative complications were pancreatic fistula (15.2%), wound infection (13.4%) and delayed gastric emptying (6.3%). Three (5%) patients had reoperation due to intra-abdominal abscess and postoperative hemorrhage. Twenty-six (55.3%) of the 47 functional tumors were malignant, whereas 40 (61.5%) of the 65 nonfunctional tumors were malignant. Survival was significantly related to the type of neuroendocrine tumor (p = 0.001). The overall 5-year actual survival rate of patients with WD-Ca (n = 54) was 56%, significantly less than that of patients with WDT (n = 46, 91%, p = 0.001). All the patients of PD-Ca (n = 12) group died in 5 years. The 5-year survival rate differed significantly between patients with tumor node metastasis (TNM) stage I and II disease and those with stage III and IV tumors (p = 0.011). Patients with stage III had better prognosis than those with stage IV tumors (p = 0.007). Patients' long-term survival was closely correlated with vascular invasion (p = 0.008) and resection margin (p = 0.004). CONCLUSIONS: PNETs can be safely resected. Microscopic vascular invasion and positive resection margin are helpful for predicting patient survival. Malignant cases should be treated with aggressive radical surgery to achieve complete tumor resection and potential for long-term survival. PMID- 20571267 TI - Long-term results of the cut-closed-reconnected Roux loop for enterogastric reflux. AB - BACKGROUND: The aim of this study was to present the long-term results of the cut closed-reconnected (CCR)-Roux procedure for reflux gastritis. METHODS: A retrospective analysis was performed on 14 patients with proven reflux gastritis and/or esophagitis who were treated at our institution with a CCR-Roux procedure between 1992 and 1997. RESULTS: The closure of the afferent loop in the CCR-Roux procedure is effective and permanent. The CCR-Roux patients did not need a rest gastrectomy. No signs of Roux stasis syndrome were seen. There was a consistent weight gain at 2 and 5 years of follow-up. These results permit a comparison with those of the Roux-Y procedure and other alternative procedures as well. CONCLUSION: In the long run, the CCR-Roux procedure is effective in the treatment of reflux gastritis. PMID- 20571268 TI - Postoperative bowel function and nutritional status following distal pancreatectomy with en-bloc celiac axis resection. AB - BACKGROUND/AIMS: Distal pancreatectomy with en-bloc celiac axis resection (DP CAR) is routinely accompanied by complete resection of the bilateral celiac ganglions and the circumferential plexus of the superior mesenteric artery. The postoperative condition including bowel movement, nutritional status, and tolerance to adjuvant chemotherapy has never been studied. METHODS: 40 patients who underwent DP-CAR were enrolled in this study. Postoperative bowel function was estimated by the requirement of anti-diarrheal agents. Changes of nutritional parameters including body weight and laboratory data for 1 year after surgery were evaluated. RESULTS: 15 (38%) patients needed no anti-diarrheal agent after a median follow-up period of 39 months. The other patients were well controlled for their bowel movement with anti-diarrheal drugs. 13 patients who received adjuvant chemotherapy tolerated it well despite hematologic toxicity in 7 patients who received gemcitabine. Postoperative body weight was significantly decreased and reached a plateau value at postoperative month 3. The values of laboratory data indicating nutritional status were significantly lower at 1 month after surgery and recovered between 3 and 12 months. CONCLUSION: The patients who underwent DP CAR scarcely suffered from intractable diarrhea and could achieve a feasible nutritional status after surgery to be able to receive adjuvant chemotherapy. PMID- 20571269 TI - Effectiveness of neoadjuvant radiotherapy in the treatment of locally advanced rectal cancer: a single-center experience in 263 patients. AB - AIM: To determine the frequency of local recurrence (LR) and distant recurrence (DR) with 5-year survival analysis. METHODS: Patients with T3-T4 rectal cancer located within 10 cm from the anal verge. Radiotherapy protocol: 36 Gy, delivered in 12 daily doses of 3 Gy each for 5 days/week, followed by surgery after a 2 week break. RESULTS: 263 patients were recruited. Radiotherapy was well tolerated. None of the patients broke off treatment. Complete histological response was 3% and maximum radio-induced downstaging 31.4%. Overall complication rate was 25.8% and direct radio-induced complications 0.4%. Mean duration of treatment was 35.7 days. In 172 patients with a minimum follow-up of 5 years, the rate of LR was 6.0% and DR 24.4%. Five-year overall survival was 70.2%, overall specific survival 78.0%, disease-free survival 70.7%, LR-free specific survival 92.9%, and DR-free specific survival 73.5%. CONCLUSIONS: In our experience, local disease control was achieved in 94% of patients. Any changes in our treatment protocols will aim at improving results in terms of LR and DR. In view of the four-fold higher rate of DR as compared to LR, improvement of DR can be defined as the challenge for the future. PMID- 20571270 TI - A simple novel model to predict hospital mortality, surgical site infection, and pneumonia in elderly patients undergoing operation. AB - BACKGROUND/AIMS: Predicting models of operative morbidity and mortality in the geriatric population are important in the prevention of adverse surgical outcomes. METHODS: A retrospective review of medical records was performed for patients over 80 years of age who underwent gastrointestinal surgery from 1998 to 2008. RESULTS: 215 patients were identified with a mean age of 83.7 years. Overall morbidity and mortality rates were 48.8 and 14.4%, respectively. Multivariate logistic regression analysis revealed that serum albumin levels [odds ratio (OR) = 0.367, p = 0.0267], postoperative pneumonia (OR = 3.471, p = 0.0101), hollow organ perforation or anastomosis combined with leakage (OR = 7.600, p = 0.0126), and preoperative systemic inflammatory response syndrome (OR = 3.186, p = 0.0323) were significant predictors of hospital mortality. Moreover, albumin (OR = 0.270, p = 0.0002) and physical disability (OR = 3.802, p = 0.0009) were significant predictors of postoperative pneumonia, and albumin (OR = 0.491, p = 0.0212) and enterotomy (OR = 3.335, p = 0.0208) were significant predictors of surgical site infections. CONCLUSION: This study provides novel predicting models to identify the elderly surgical patients at high risk, who should receive more intensive preventive and perioperative care. PMID- 20571271 TI - Inflammation-based prognostic score and number of lymph node metastases are independent prognostic factors in esophageal squamous cell carcinoma. AB - BACKGROUND/AIMS: Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, is useful for postoperative prognosis of esophageal squamous cell carcinoma. METHODS: GPS was calculated on the basis of admission data as follows: patients with elevated C-reactive protein level (>10 mg/l) and hypoalbuminemia (<35 g/l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0. A new scoring system was constructed using independent prognostic variables and was evaluated on whether it could be used to dictate the choice of clinical options. RESULTS: 65 patients with esophageal squamous cell carcinoma were enrolled. GPS and the number of lymph node metastases were found to be independent prognostic variables. The scoring system comprising GPS and the number of lymph node metastases was found to be effective in the prediction of a long-term outcome (p < 0.0001). CONCLUSIONS: Preoperative GPS may be useful for postoperative prognosis of patients with esophageal squamous cell carcinoma. GPS and the number of lymph node metastases could be used to identify a subgroup of patients with esophageal squamous cell carcinoma who are eligible for radical resection but show poor prognosis. PMID- 20571272 TI - Multivisceral resection for colon cancer: analysis of prognostic factors. AB - BACKGROUND/AIMS: To assess outcome of multivisceral resection in colon cancer patients and to identify predictors of survival. METHODS: One hundred and thirteen consecutive patients with primary locally advanced colon cancer infiltrating adjacent organs undergoing multivisceral resection between 1998 and 2007 were reviewed. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method. The relative risk for clinical outcome was obtained using a Cox multivariate model. RESULTS: The median follow-up was 74.9 months. Fifty-two patients had sigmoid tumors and 48 involvement of the small intestine. Complications occurred in 54 patients. The diagnosis was conventional adenocarcinoma in 94 patients. R0 resection was achieved in 96 patients (85%). Eighty-three patients received postoperative adjuvant therapy. The operative mortality was 7.1% (8 patients). Sixty-seven patients died at follow-up. Of the 46 patients who were alive, 38 were free of disease. In 73 patients with pT4a disease, 42 patients died (57.5%) and of the 31 survivors, recurrence was documented in 6. Hematochezia and adjuvant chemotherapy were independent factors of favorable outcome and grade G3 and tumor stage III-IV of poor survival. CONCLUSION: Hematochezia and adjuvant chemotherapy were associated with a better survival, and poorly differentiated tumors and stage IV disease with a poor survival. PMID- 20571273 TI - Ulcer size and gastric cancer. PMID- 20571274 TI - Ulcer size and gastric cancer prognosis. PMID- 20571275 TI - Clinical characteristics and brain activation patterns of mirror movements in patients with corona radiata infarct. AB - OBJECTIVE: Mirror movements (MMs) are a phenomenon of involuntary movements that accompany physically intended movements of the opposite side of the body. In the current study, we investigated the clinical characteristics and cortical activation patterns of MMs in patients with corona radiata (CR) infarct, using functional MRI. SUBJECTS AND METHODS: We recruited 31 consecutive hemiparetic stroke patients with CR infarct. Functional MRI was performed to verify brain activation patterns during grasp-release movements of the affected hand, and MM of the unaffected hand was observed simultaneously. RESULTS: The prevalence of MMs was 54.8% (17 out of 31 patients), and the intensity of MMs ranged from mild to moderate. The severity of MM in the unaffected hand is closely related to the poor motor function of the affected upper extremity and to activations of the unaffected motor cortex and both supplementary motor areas (SMAs) during the movement of the affected hand. In addition, the activations of unaffected motor cortex and both SMAs were closely related to poor motor function of the affected upper extremity. CONCLUSIONS: The results suggest that MMs, poor motor function, and the activations of ipsilateral motor cortex and both SMAs are closely interconnected in patients with CR infarct. PMID- 20571276 TI - Treatment of metachronous and simultaneous liver metastases of pancreatic cancer. AB - AIM: Patients were analyzed who underwent treatment of liver metastases from pancreatic cancer. METHODS: Selection criteria were the possibility of R0 resection of the primary and/or the liver metastases, no other sites of metastases, and the presentation of liver metastases. A comparison of treatment by surgery versus chemotherapy regarding overall survival and disease-free interval was performed. RESULTS: Between 1996 and 2008, a total number of 23 patients were retrospectively identified from a prospective database of 193 cases of pancreatic cancer. In 14 cases, liver metastases were found simultaneously, and in 9 cases metachronously, fulfilling the abovementioned selection criteria. Of these, 13 patients underwent surgery and 10 were treated by gemcitabine. There were no differences in survival in patients with synchronous liver metastases of pancreatic cancer treated by resection of the primary combined with partial hepatectomy versus treatment by gemcitabine (8 vs. 11 months). In patients with metachronous liver metastases, the median survival was increased after liver resection compared to patients who were treated with gemcitabine (31 vs. 11 months). CONCLUSIONS: Simultaneous resection of pancreatic cancer and liver metastases cannot be recommended. Resection of metachronous liver metastases of pancreatic cancer seems to improve survival in highly selected patients. PMID- 20571277 TI - RCAS-1 serum and tumor levels in head and neck squamous cell carcinoma. AB - BACKGROUND/AIMS: RCAS-1 is a transmembrane protein that is involved in the evasion of host immune surveillance by tumor cells. It has been found to be a valuable prognostic and diagnostic marker in a number of different malignancies. The objective of the study was to analyze the potency of RCAS-1 as a biomarker in the serum of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: ELISA was performed with prospectively collected serum samples from 60 patients with HNSCC (taken at the time of diagnosis, after 3 and 12 months) and from 31 healthy controls. To correlate serum levels with RCAS-1 expression in the tumor, immunohistochemical staining of RCAS-1 was done using a tissue microarray. RESULTS: Surprisingly, median sRCAS-1 levels were basically identical between tumor patients and controls. Interestingly, patients with low RCAS-1 values at the time of diagnosis had better disease-free survival. 62% of tumor samples expressed RCAS-1 but we could not demonstrate a correlation between protein expression and serum levels. CONCLUSION: This study was the first to correlate RCAS-1 levels in the serum and in the tumor of the same patients. RCAS-1 seems to have prognostic properties although larger studies will be necessary to fully evaluate its role in HNSCC. PMID- 20571278 TI - Eplerenone suppresses salt-induced vascular endothelial growth factor expression in the kidney. AB - BACKGROUND/AIM: It is well accepted that high dietary salt intake accelerates both hypertension and target organ damage. We have previously shown that eplerenone attenuates sustained elevated systolic blood pressure in Dahl salt sensitive (SS) rats. In the present study, we investigated the role of eplerenone on vascular endothelial growth factor (VEGF) expression because we suspected that eplerenone treatment may trigger a unique mechanism that relies on the downregulation of VEGF. METHODS: Dahl SS rats were fed a high salt (8% NaCl) diet for 3 weeks and then switched to normal salt (0.3% NaCl) diet with or without treatment with eplerenone (100 mg/kg/day), enalapril (30 mg/kg/day) and their combination for an additional 3 weeks. RESULTS: In addition to reducing blood pressure, eplerenone inhibited glomeruli sclerosis and suppressed the expression of VEGF and endothelial nitric oxide synthase mRNA as well as protein levels. CONCLUSIONS: Based on these findings, we suggest that in part, VEGF stimulation of endothelial nitric oxide synthase plays a significant role in the eplerenone induced reversal of the renal and vascular damage caused by high dietary salt intake. PMID- 20571279 TI - Protein nutrition index as a function of patient survival rate in peritoneal dialysis. AB - BACKGROUND/AIMS: Protein-energy wasting (PEW) is a well-known risk factor of long term survival in peritoneal dialysis (PD) patients. Serum albumin is a measure of visceral protein, lean body mass is a measure of somatic protein stores and normalized protein nitrogen appearance is a measure of daily protein intake. A protein nutrition index (PNI) that combined these 3 factors was designed and tested as a function of survival in PD patients. METHODS: We enrolled 552 PD patients for this study. Demographic, biochemical, nutritional markers, comorbidity and dialysis-related data were obtained. The PNI was calculated. All patients were followed up to investigate the risks for mortality. RESULTS: Patients with probable PEW/low-average nutrition were older and had lower serum creatinine (Cr) and blood urea nitrogen, lower adequacy data and higher D4/P4 Cr compared with patients with high-average/good nutrition. 108 patients (19.6%) died during the observational period. By multivariate analysis, we found only age, comorbidity index and PNI (relative risk = 0.84, confidence interval: 0.76 0.93, p = 0.001) to be independent predictors of mortality. CONCLUSION: The PNI at the start of PD is associated with all-cause mortality, and each increase by a score of 1 in PNI leads to a 16% decrease in the risk of mortality. Predialysis evaluation of this scoring system is recommended for further research in order to improve outcomes in PD patients. PMID- 20571280 TI - Low-flow polytetrafluoroethylene accesses: ultrasound surveillance and preemptive interventions ensure long-term patency. AB - BACKGROUND: Vascular accesses (especially polytetrafluoroethylene grafts) with a permanently low flow (Qa <600 ml/min) are prone to thrombosis and thus have short patency. The reason for a permanently low flow is usually medial calcinosis of the inflow artery in diabetics. We retrospectively studied the long-term patency of low-flow grafts with careful ultrasound surveillance and preemptive interventions. METHODS: Twenty subjects with Qa permanently <600 ml/min were included. Ultrasound surveillance was performed every 3 months in addition to classical monitoring techniques. Significant stenosis was strictly defined as the combination of B-mode narrowing >50% + >2-fold peak systolic velocity increase + 1 additional criterion (residual diameter <2.0 mm or flow volume decrease by >20%). Such stenoses were treated by preemptive percutaneous intervention. Primary and secondary patencies were calculated. RESULTS: The primary patency was 357 +/- 316 days and the secondary (cumulative) patency was 996 +/- 702 days. The number of interventions was 2.09/patient year, but >10 in 6 (33%) subjects. 93 and 80% of grafts were patent 1 and 2 years after access creation, respectively. CONCLUSION: Low-flow accesses undergoing ultrasound surveillance with strict diagnostic criteria and preemptive interventions had patencies similar to accesses with normal Qa in our study. This was enabled by a relatively high rate of interventions. PMID- 20571281 TI - Role of Fosinopril and Valsartan on Klotho Gene Expression Induced by Angiotensin II in Rat Renal Tubular Epithelial Cells. AB - BACKGROUND/AIMS: Klotho gene, a new anti-aging gene, is mainly expressed in the kidney tubules. Several studies have found the relationship between klotho and emergence and development of renal diseases. This study set out to explore the role of fosinopril (Fos) and valsartan (Val) on klotho expression induced by angiotensin II (Ang II) in rat renal tubular epithelial cells (NRK-52E). METHODS: NRK-52E cells were divided into five groups according to the treatment of Ang II, Fos and Val. Transforming growth factor-beta1 (TGF-beta1), p38, phospho-p38 (p p38), p53, and Sp1 protein expression were determined by immunohistochemical and Western blotting analysis. Klotho expression was detected by reverse transcription-polymerase chain reaction and Western blotting analysis. RESULTS: Ang II upregulated TGF-beta1, p-p38 and p53 expression, and inhibited Sp1 and klotho expression in NRK-52E cells. After the intervention of Fos and/or Val, TGF beta1, p-p38 and p53 expression were downregulated, Sp1 and klotho expression were upregulated. TGF-beta1 and p53, Sp1 and klotho expression exhibited a positive linear correlation, respectively. CONCLUSION: We conclude that Fos and Val have a protective role in Ang II-induced renal damage, and it may be through mechanism of inhibiting TGF-beta1, p-p38 and p53 expression, thus upregulating Sp1 and klotho expression. PMID- 20571282 TI - Mediterranean weather conditions and exacerbations of multiple sclerosis. AB - BACKGROUND: Previous studies provide increasing support for the impact of environmental factors on disease incidence and activity in multiple sclerosis (MS). OBJECTIVES: The purpose of this research was to assess the relationship between the incidence of MS relapses and weather conditions in Israel. METHODS: Clinical data, including occurrence of relapses in 235 patients, during 3 consecutive years (2001-2003) were assessed against the general daily meteorological variables. Initially, the relationship between the relapses and their mode of distribution was evaluated. Second, the relationship between the number of relapses on a specific date and the meteorological variables was assessed. Third, the tendency to seasonality in the occurrence of relapses was examined. RESULTS: No significant correlation was found between the number of relapses and a specific season, month or day. Moreover, no clear relationship was found between certain meteorological variables or a combination of variables and the frequency of the relapses. CONCLUSION: The meteorological parameters studied were not found to have a significant impact on the occurrence of relapses in this group of patients. These findings raise questions regarding the clinical significance of the impact of weather conditions, at least in the context of the Mediterranean climate, on the disease course of patients with MS. PMID- 20571283 TI - Occurrence of PARK2 mutations in a never-smoker population with Parkinson's disease in North India. AB - BACKGROUND: Parkinson's disease (PD) is a complex neurological disorder without any well-documented genotype-demography associations among sporadic variants. We recently reported PARK2 mutations to be constituting 40% of PD in this region and thus analysed how demographic variables associate with PARK2 mutations in 70 of these patients. METHODS: PD samples were screened by PCR single-strand conformation polymorphism (SSCP) and sequencing and their demographic data collected. Demographic and religion data was obtained from 1,010 randomly selected individuals of 120,000 patients visiting the Neurology Clinic and was compared with state database and PD patients. RESULTS: Sikhs from a rural background exhibited the majority of PARK2 mutations. The frequency of PARK2 mutations among females was significantly higher as compared to males (p < 0.015). The age of onset of PD patients with a rural background was found to be significantly lower as compared to patients with an urban background (p < 0.004). The demographic spectrum of the 1,010 randomly selected patients and the background population was found to be comparable. CONCLUSIONS: As PD patients with PARK2 mutations were found to be of sporadic origin and never-smokers, a non redundant inverse relationship between founder PARK2 mutations and smoking is implicated to account for its high frequency. The predisposition of Sikhs to PARK2 mutations necessitates a larger study among its familial variants and a control smoker PD population. The spectrum of PARK2 mutations among Sikh smokers is difficult to study because of the religion-based aversion to smoking. PMID- 20571284 TI - Acupuncture in tension-type headache. PMID- 20571285 TI - Very early versus delayed mobilisation after stroke. PMID- 20571286 TI - Stroke awareness in Denmark. AB - BACKGROUND: This is the first study to examine the awareness of major stroke symptoms and stroke risk factors among the general population in Denmark. Early recognition of stroke warning signs and means of reducing stroke occurrence could improve the treatment and prevention of stroke. METHODS: A total of 3,520 subjects were invited to participate in the study, using a web-based, closed questionnaire. The recruitment was stratified by region, age and gender to represent the composition of the general Danish population aged 40+ years. Enrollment was competitive with a predefined target of 800 responses. The subjects were asked to rank the 4 most important acute stroke symptoms, and the 3 most important risk factors for stroke. Multivariable ordinal logistic regression was used for assessing factors associated with awareness of stroke symptoms and major stroke risk factors. RESULTS: From December 12 to December 17, 2008, a total of 811 subjects (mean age: 58 years; SD: 11 years) were included, of which 405 (50%) were women. The 4 most frequently identified stroke symptoms were sudden onset of: speech disturbances (n = 636; 78.4%), facial palsy (n = 450; 55.5%), hemiparesis (n = 435; 53.6%) and visual disturbances (n = 429; 52.9%). The 3 most frequently identified stroke risk factors were: hypertension (n = 586; 72.3%), history of cerebrovascular disease (n = 401; 49.5%) and high concentration of cholesterol (n = 269; 33.2%). Compared with men, women had better knowledge of major stroke symptoms (OR = 1.33; 95% CI: 1.12-1.50) and stroke risk factors (OR = 1.33; 95% CI: 1.10-1.51) in multivariable analyses. CONCLUSIONS: The awareness of major stroke symptoms is insufficient. Whereas hypertension was the most often mentioned stroke risk factor, few subjects recognized tobacco smoking and diabetes mellitus as major risk factors for stroke. PMID- 20571287 TI - Charcot-Marie-Tooth disease in Cyprus: epidemiological, clinical and genetic characteristics. AB - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. CMT is classified into 2 main subgroups: a demyelinating and an axonal type. Further subdivisions within these 2 main categories exist and intermediate forms have more recently been described. Inheritance can be autosomal dominant, recessive or X-linked. CMT is associated with more than 30 loci, and about 25 causative genes have been described thus far. METHODS: We studied epidemiological, clinical and genetic characteristics of CMT in the Cypriot population. RESULTS: The prevalence of CMT in Cyprus on January 15, 2009, is estimated to be 16 per 100,000. Thirty-three families and 8 sporadic patients were ascertained. CMT was demyelinating in 52%, axonal in 33% and intermediate in 15% of the patients. Thirteen families had PMP22 duplication, 3 families had the PMP22 S22F mutation, 4 families had GJB1/Cx32 mutations, 2 families had different MPZ mutations, 1 of them novel, and 2 families had different MFN2 mutations. Nine families and 8 sporadic patients were excluded from the common CMT genes. CONCLUSION: The most frequent CMT mutation worldwide, the PMP22 duplication, is also the most frequent CMT mutation in the Cypriot population. Five out of the 8 other mutations are novel, not reported in other populations. PMID- 20571288 TI - Effects of cholesterol and its 24S-OH and 25-OH oxysterols on choline acetyltransferase-positive neurons in brain slices. AB - In Alzheimer's disease (AD) neurons expressing the enzyme choline acetyltransferase (ChAT) degenerate and a loss of cholinergic activity directly correlates with cognitive decline. Recent studies have suggested that cholesterol plays a role in AD. The aim of the present study was to explore if cholesterol and its oxysterols, 24S-hydroxycholesterol (24S-OH Chol) and 25 hydroxycholesterol (25-OH Chol), affect ChAT-positive neurons in organotypic brain slices of the basal nucleus of Meynert (nBM). We showed that slices expressed approximately 140 ChAT-positive neurons/slice after 2 weeks when incubated with nerve growth factor (NGF). This number markedly decreased when incubated without NGF to approximately 20 neurons/slice. Cholesterol and 24S-OH Chol delayed this decrease in ChAT-positive neurons. In contrast, 25-OH Chol induced a decline in ChAT-positive neurons in 2-week-old slices within 4 days. The effects of cholesterol and its oxysterols were exhibited in a dose- and time dependent way. Our results show that cholesterol and 24S-OH Chol delays the decrease in ChAT-positive neurons, while 25-OH Chol rapidly decreases ChAT expression, suggesting differential mechanisms on ChAT expression in cholinergic nBM neurons. PMID- 20571290 TI - Immune factors in human embryo culture and their significance. AB - There is increasing evidence that human development before implantation is regulated by embryonically and maternally derived growth factors. The "regulators" of embryonic origin such as soluble human leukocyte antigen G, platelet-activating factor, Th1/Th2 cytokines, insulin-like growth factor, epidermal growth factor, transforming growth factor alpha, colony-stimulating factor, platelet-derived growth factor may be used as indicators of embryo viability and implantation potential. The data prove the influence of growth factors on the development and growth of preimplantation embryos. Though there is a lot of research in the field of biomarkers during folliculogenesis and maternal fetal interface, only few of them deal with regulators derived from embryonic cells to the cultivation medium. The aim of our study was to summarize the research dealing with immune markers produced by embryos in vitro and to estimate their impact on the cell growth, viability and implantation potential. PMID- 20571291 TI - Tigecycline - how powerful is it in the fight against antibiotic-resistant bacteria? AB - Tigecycline is a semisynthetic analogue of earlier tetracyclines and represents the first member of a novel class of antimicrobials - glycylcyclines - recently approved for clinical use. It is active against a broad range of gram-negative and gram-positive bacterial species including clinically important multidrug resistant nosocomial and community-acquired bacterial pathogens. The exact molecular basis of tigecycline action is not clear at present, although similarly to the tetracyclines, it has been shown to inhibit the translation elongation step by binding to the ribosome 30S subunit and preventing aminoacylated tRNAs to accommodate in the ribosomal A site. Importantly, tigecycline overcomes the action of ribosomal protection proteins and is not a substrate for tetracycline efflux pumps of most bacteria - well-known and prevalent cellular mechanisms of microbial tetracycline resistance. The present review summarizes current knowledge on the molecular mechanism of the tigecycline action, antibacterial activity against various bacteria, clinical application, development of resistance to glycylcyclines. PMID- 20571289 TI - Sun-induced changes in stratum corneum function are gender and dose dependent in a Chinese population. AB - Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18-50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID- 20571292 TI - Interventional and surgical management of abdominal compartment syndrome in severe acute pancreatitis. AB - BACKGROUND AND OBJECTIVE: Management of the abdominal compartment syndrome during severe acute pancreatitis by the open abdomen method is associated with considerable morbidity and resource utilization. Thus, the aim of this study was to evaluate the safety and efficacy of the ultrasound-guided percutaneous interventions and/or minimally invasive surgery in the treatment of abdominal compartment syndrome. MATERIAL AND METHODS: Forty-four patients with severe acute pancreatitis were enrolled into a prospective study and treated according to the standard management protocol. Interventional and/or surgical management of abdominal compartment syndrome was employed in 6 (13.6%) cases. In the context of this study, we assessed the feasibility and effectiveness of subcutaneous fasciotomy of the anterior m. rectus abdominis sheath, as well as the role of ultrasound-guided drainage of intra-abdominal and peripancreatic fluid collections in the management of abdominal compartment syndrome. RESULTS: Subcutaneous fasciotomy of the anterior m. rectus sheath and ultrasound-guided drainage of intra-abdominal and peripancreatic fluid collections seem to be safe (minor risk of bleeding or infection, closed abdomen, and easy care for the patient) and effective (resulted in a sustained decrease of intra-abdominal pressure to 13-16 mm Hg and regression of organ failures after intervention). Subcutaneous anterior m. rectus fasciotomy may appear to be beneficial in case of refractory abdominal compartment syndrome avoiding morbidity associated with the open abdomen technique. CONCLUSIONS: Both the subcutaneous fasciotomy and ultrasound-guided drainage of intra-abdominal and/or peripancreatic fluid collections seem to be safe and effective alternatives in the management of abdominal compartment syndrome; however, prospective studies are needed to further evaluate their clinical role. PMID- 20571293 TI - Clinical characteristics and long-term outcomes of 35 patients with Wegener's granulomatosis followed up at two rheumatology centers in Lithuania. AB - OBJECTIVE: The aim of this study was to investigate the survival of Lithuanian patients with Wegener's granulomatosis, who were followed up at two tertiary rheumatology centers, and to find the factors possibly influencing the outcomes of this disease. MATERIAL AND METHODS: Thirty-five patients were followed up prospectively from the onset of disease (the first patient was enrolled in 1994) at Vilnius University Hospital and the Center of Rheumatology of Kaunas University of Medicine (17 and 18 patients, respectively). All patients in both the centers were followed up on a routine basis, and their records contained necessary information about laboratory and biopsy data; the censoring date (end of follow-up) was stated in June 2006. RESULTS: Among the patients, the most frequent organs involved were ear, nose, throat (ENT) (82.6%), lungs (74.3%), and kidney (renal involvement was defined by proteinuria/abnormal urine sediment) (45.7%). Renal insufficiency was present in 20.6% of all the patients. At the end of the study, 32.4% of patients had simultaneously all three organ systems involved, namely upper respiratory tract, pulmonary, and renal. ANCA positivity was found for 26 (74.3%) of all the patients. Overall mortality rate was 25.7% (9/35). The mean survival was 99.4 months (95% CI, 73.6; 125.3) limited to 149 months for the longest-surviving patient. CONCLUSIONS: Female gender and all three specific organ involvements being present at the same time and higher vasculitis damage index were associated with poor outcome. Overall mortality rate was 25.7% (9/35) during the 12-year follow-up, and it is similar to the data from other European countries. PMID- 20571294 TI - The influence of dexamethasone and ketolgan on postoperative nausea and vomiting and estimation of risk factors in women undergoing gynecologic laparoscopic surgeries. AB - The aim of this study was to determine the effect of dexamethasone and ketolgan on postoperative nausea and vomiting and to evaluate risk factors for postoperative nausea and vomiting. MATERIAL AND METHODS: A prospective, double blind, randomized clinical study was carried out. One hundred fifty-three ASA I II women undergoing laparoscopic gynecologic operations were randomized into three groups: dexamethasone group (n=51), ketolgan group (n=51), and control group (n=51). Patients in the dexamethasone group were given 4 mg of dexamethasone intravenously before the induction of general anesthesia, the ketolgan group received 30-mg ketolgan intravenously, and control group did not receive any medication. The incidence and severity of postoperative nausea and vomiting were registered 24 hours after the surgery. RESULTS: The incidence of postoperative nausea and vomiting in the dexamethasone group was 13.8%; in the ketolgan group, 37.3%, and in the control group, 58.9% (P=0.026). Patients with a history of migraine suffered from postoperative nausea and vomiting in 70.3% of cases and migraine-free patients in 25.8% of cases (P=0.015). Opioids for postoperative analgesia increased the incidence of postoperative nausea and vomiting as compared with nonsteroidal anti-inflammatory drugs (P=0.00002). CONCLUSIONS: Preoperative medication with dexamethasone significantly reduces the incidence of postoperative nausea and vomiting. Avoidance of opioids for postoperative analgesia reduces the incidence of postoperative nausea and vomiting. Migraine and motion sickness are independent risk factors for postoperative nausea and vomiting. PMID- 20571295 TI - [Outcomes of long-term combined treatment in follicular thyroid carcinoma]. AB - The aim was to analyze the impact of combined treatment (thyroidectomy + radioactive iodine treatment + hormonotherapy with thyroxine) on the outcomes of patients with follicular thyroid carcinoma. MATERIAL AND METHODS: This retrospective study included 448 patients with follicular carcinoma (394 females, 54 males, mean age of 48 years (95% CI, 46-50 years) who were treated at the Institute of Oncology, Vilnius University, from 1982 to 2006. All the patients underwent thyroidectomy. Hypothyroid patients 3-12 weeks after surgical treatment were treated with moderate radioiodine doses (1.11-3.7 GBq), and these doses were administered every 3-4 months. The patients with follicular thyroid carcinoma were given suppressive doses of thyroxine after combined treatment. The patients treated were regularly observed by gamma camera; every 6-12 months, serum thyroglobulin was evaluated. RESULTS: The remnants of thyroid tissue were detected in all 448 patients after thyroidectomy and radioiodine therapy. Radioiodine at mean total doses of 5.6+/-0.2 GBq was used to destroy the remnants of thyroid tissue. For patients with disseminated forms of follicular thyroid carcinoma, mean total radioiodine doses of 19.5+/-3.1 GBq were used. Majority (91.2%) of the patients were euthyroid or hyperthyroid after the treatment with thyroid hormone. All the patients treated had the level of serum thyroglobulin of 1.1+/-0.2 ng/mL. The overall 10-, 20-, and 30-year survival of patients with follicular thyroid cancer, who received combined treatment, was 91.2%, 81.9%, and 77.1%, respectively. CONCLUSION: Combined treatment (thyroidectomy + radioactive iodine treatment + hormonotherapy with thyroxine) administered to the patients with follicular thyroid carcinoma is highly effective, because overall 10-, 20-, 30-year survival was 91.2%, 81.9%, 77.1%, respectively. PMID- 20571296 TI - Secondary thrombosis of the left internal carotid artery caused by a motor vehicle accident: a radiological case. AB - A rare case of occlusion of the internal carotid artery following a motor vehicle accident in a 34-year-old female victim who initially presented with clear consciousness and had normal computed tomogram of the brain is reported. Seven hours after the accident, the patient was unexpectedly diagnosed with the left hemisphere infarction, and two days later, she suffered from right hemiplegia and coma. The follow-up brain computed tomography scan showed an acute infarction of the left hemisphere of the cerebrum and severe cerebral edema. Anticoagulation therapy was administered, and emergency craniotomy for brain decompression was carried out. After 3.5 months, she was discharged and underwent regular follow-up in the outpatient department. Four years after the motor vehicle accident, the patient had intact awareness, was functionally independent, but remained with motor aphasia, right hand paralysis, and right leg paresis. PMID- 20571297 TI - Meningovascular neurosyphilis: a report of stroke in a young adult. AB - A young adult patient with meningovascular neurosyphilis in the form of acute ischemic stroke with right hemiparesis and speech disturbance is reported. CT scan showed features of ischemic infarct and extensive laboratory studies were made before the diagnosis ultimately was revealed. Such cases could result in confusion for the clinician, and high index of clinical suspicion of this condition is required since syphilis is not routinely tested, as routine screening is seen to be of low diagnostic yield. As clinical practice indicates, it remains a difficult problem approaching diagnosis of neurosyphilis, and this is achieved through exclusion of neurosyphilis as a clinical possibility. PMID- 20571298 TI - Cost-utility analysis of methadone maintenance treatment in Lithuania. AB - BACKGROUND: Economic evaluations in health care involve the identification, measurement, valuation, and then comparison of the costs (inputs) and outcomes of treatments or preventive activities. The aim was to analyze the cost-utility of six-month methadone maintenance treatment program in a Lithuanian primary health care setting. METHODS: A prospective study design was used. All the information was obtained through the validated questionnaires at the baseline and 3- and 6 month follow-ups. WHOQOL-BREF was used to assess the quality of life; the costs were assessed using the DATCAP methodology from the perspective of a patient and outpatient clinic during follow-up period. RESULTS: A total of 102 opioid dependent patients were recruited in the study; 512 follow-up patient-months were obtained. The methadone maintenance treatment has significantly improved physical, psychological, and environmental components of quality of life during follow-up. Total program costs were 61 288.87 EUR. Cost paid by a patient comprised about 31% of total program costs. Cost per quality-adjusted life-month (QALM) for physical domain was 2227.55 EUR; for psychological domain, 1879.50 EUR; for social domain, 5467.64 EUR; and for environmental domain, 4626.47 EUR. Costs per QALM and quality-adjusted life-year (QALY) for total quality of life in the maintenance program were 2864.00 EUR and 34 368.00 EUR, respectively. CONCLUSIONS: Our results showed that 6-month methadone maintenance program was effective in the terms of quality-of-life improvement. Methadone maintenance treatment program was less effective in terms of cost per QALY. PMID- 20571299 TI - [Combined oral contraception and hypercoagulation]. AB - Combined oral contraceptives have been known as a well-established contraceptive method already more than 50 years. Unfortunately, this method is not absolutely safe. Combined oral contraceptives include estrogens and progestagens, which may stimulate the blood coagulation and promote the occurrence of deep-vein thrombosis; adverse effects of oral contraceptives are also notably associated with increased risk of stroke and myocardial infarction. The risk of hypercoagulation and venous thrombosis is most likely to be influenced by the dose of estrogens, but recent investigations have showed that the type of progestagens is very important as well. PMID- 20571300 TI - [A case of hyperplastic polyp at distal common bile duct]. PMID- 20571301 TI - [Steatocholecystitis]. PMID- 20571302 TI - [Liver transplantation in patients with hepatocellular carcinoma]. AB - Hepatocellular carcinoma (HCC) is the third most common malignancy, with a new incidence of more than 11,000 cases per year and the second most common cause of malignancy-related death in Korean males. In Korea, more than 80% of all HCCs have developed from hepatitis B virus (HBV)-related cirrhotic livers. Liver transplantation (LT) is the only treatment that offers a chance of cure for HCC and the underlying liver cirrhosis simultaneously, but the availability of liver grafts and the aggressiveness of tumor recurrence are critical limiting factors of LT for HCC patients. The serious shortage of deceased-donors on strong demand for LT leads to the development of living-donor LT (LDLT) as a practical alternative replacing deceased-donor LT. Considering that HCC recurrence is the most common cause of posttransplant patient death, recipient candidates should be prudently selected through objectively established criteria. Uniquely, some Asian major LDLT centers challenged the Milan criteria, accepting a much higher number of HCC nodules instead of tumor size expansion. The eligibility criteria of LDLT for HCC are likely to be expanded more than before, but it still requires further qualified risk-benefit analyses. The development of new effective treatment modalities for HCC recurrence will reasonably expand the selection criteria further wide without the expense of recurrence rate. This article is mainly focused on the role of LT for HCC and discussed on the validity of currently available indication criteria. PMID- 20571303 TI - [Clinical characteristics of 17 cases of eosinophilic gastroenteritis]. AB - BACKGROUND/AIMS: Eosinophilic gastroenteritis (EG) is a rare disease characterized by prominent eosinophilic infiltration that may involve a variable depth of one or more gastrointestinal organs. We analyzed the largest number of patients with EG among the studies carried out at a single center in Korea. METHODS: We retrospectively analyzed the clinical, laboratory, endoscopic, and radiologic features, management, and clinical outcome in 17 patients who were diagnosed as EG from January 1994 to February 2008. RESULTS: Median age was 36 (2 67 years). Two of the 17 patients had a history of allergy. The most common symptoms were abdominal pain and diarrhea. Fifteen patients (88.2%) had hypereosinophilia. The ESR was moderately raised in 6 out of 14 patients. Eleven patients (64.7%) had predominant involvement of the mucosa, 1 (5.9%) of muscularis, and 5 (29.4%) of subserosa. EGD revealed non-specific findings such as erythema and edema. Abdominal Computed tomography revealed gastrointestinal wall thickenings of the involved organ, and all of 5 cases of the subserosal type had ascites. Thirteen patients (76.5%) were improved by corticosteroid treatment. Among five patients who had been followed for more than one year (12-84 months), two experienced relapse after discontinuing corticosteroids. CONCLUSIONS: EG should be considered in the differential diagnosis of unexplained gastrointestinal symptoms even in the absence of peripheral eosinophilia and in non-specific endoscopic findings. PMID- 20571304 TI - [The trend of eradication rate of Helicobacter pylori infection and clinical factors that affect the eradication of first-line therapy]. AB - BACKGROUND/AIMS: Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first-line anti-Helicobacter pylori treatment, the recent trend of eradication rates following this therapy has been declined in the last few years. The purpose of this study was to investigate the trend of H. pylori eradication rates over the last 9 years and to evaluate are clinical factors affecting eradication rates. METHODS: From January 2001 to June 2009, H. pylori eradication rates in 709 patients with documented H. pylori infection who received triple combination therapy for 7 days were retrospectively evaluated according to years and various clinical factors. H. pylori status was evaluated by 13C urea breath test 4-6 weeks after completion of treatment. results: The overall H. pylori eradication rate was 77.0%. The annual eradication rates from year 2001 to 2009 were 78.9%, 72.5%, 81.0%, 75.0%, 79.1%, 77.1%, 77.8%, 77.8%, and 75.0% by per-protocol analysis. There was no decreasing tendency of the eradiation rate over 9 years (p=0.974). There was no statistical difference in the eradication rates according to age, sex, smoking, alcohol, NSAIDs, underlying diseases, endoscopic diagnosis, and PPI. However, the eradication rate was lower in patients who took aspirin (OR=0.509, 95% CI=0.292-0.887, p=0.001) and antibiotics within 6 months (OR=0.347, 95% CI=0.183-0.658, p=0.001). CONCLUSIONS: The H. pylori eradication rate has not changed at Gwangju-Chonnam province in Korea for recent 9 years. Lower eradication rate in aspirin and antibiotics users warrants further attention. PMID- 20571305 TI - [The usefulness of in vitro interferon-gamma assay for differential diagnosis between intestinal tuberculosis and Crohns disease]. AB - BACKGROUND/AIMS: It is difficult to clinically and endoscopically differentiate intestinal tuberculosis (ITB) and Crohns disease (CD). The aim of this study was to evaluate the usefulness of in vitro interferon-gamma (INF-gamma) assay for differential diagnosis between ITB and CD. METHODS: Sixty patients for whom differential diagnosis between ITB and CD was difficult were enrolled between January 2007 and January 2009. The INF-gamma-producing T-cell response to early secreted antigenic target 6 and culture filtrate protein 10 were measured by T SPOT.TB blood test in vitro. We evaluated the usefulness of T-SPOT.TB blood test by comparing its results with the final diagnosis. RESULTS: Twenty and forty patients were revealed to be positive and negative in T-SPOT.TB blood test, respectively. Of the 20 patients found to be positive, 12 patients (60%) were finally diagnosed as ITB, 6 patients as CD, and 2 patients as Behcets enterocolitis. Of the 40 patients with negative results, 38 patients (95%) were diagnosed as CD; one as Behcets enterocolitis; one as nonspecific colitis; none as ITB. The sensitivity and specificity of T-SPOT.TB blood test for ITB were 100% and 83.3%, respectively. Positive and negative predictive values of T-SPOT.TB blood test for ITB were 60.0% and 100%, respectively. CONCLUSIONS: When differential diagnosis between ITB and CD is difficult, T-SPOT.TB blood test may be a helpful and rapid diagnostic tool to exclude ITB. Prospective large-scaled studies are required for further evaluation of the usefulness of T-SPOT.TB blood test for differential diagnosis between ITB and CD. PMID- 20571307 TI - [A case of jeujunogastric intussusception presented with hematemesis after distal gastrectomy]. AB - Adult intussusception represents 5% of all cases of intussusception and accounts for only 1-5% intestinal obstructions. Intussusception is a rare complication after gastric surgery with an incidence estimated at 0.1%. Early diagnosis of the acute onset intussusception is critical because mortality rates increase abruptly with delay in surgical treatment. We present here a case of jejunogastric intussusception diagnosed by gastroscopy in a patient with a history of distal gastrectomy due to early gastric cancer who had experienced hematemesis. PMID- 20571306 TI - Effects of carnitine on peripheral blood mitochondrial DNA copy number and liver function in non-alcoholic fatty liver disease. AB - BACKGROUND/AIMS: Functional and anatomical abnormalities of mitochondria play an important role in developing steatohepatitis. Carnitine is essential for enhanced mitochondrial beta oxidation through the transfer of long-chain fatty acids into the mitochondria. We examined the impact of carnitine complex on liver function and peripheral blood mitochondria copy number in NAFLD patients. METHODS: Forty five NAFLD patients were enrolled. Patients were categorized into the carnitine complex-administered group and control group. Before and 3 months after drug administration, a liver function test and peripheral blood mitochondrial DNA and 8-oxo-dG quantitive analysis were conducted. RESULTS: In carnitine treatment group, ALT, AST, and total bilirubin were reduced after medication. There was no difference in AST, ALT, and total bilirubin between before and after treatment in control group. In carnitine group, peripheral mitochondrial DNA copy number was significantly increased from 158.8+/-69.5 copy to 241.6+/-180.6 copy (p=0.025). While in control group the mitochondrial copy number was slightly reduced from 205.5+/-142.3 to 150.0+/-109.7. 8-oxo-dG level was also tended to decrease in carnitine group (p=0.23) and tended to increase in control group (p=0.07). CONCLUSIONS: In NAFLD, the carnitine improved liver profile and peripheral blood mitochondrial DNA copy number. This results suggest that carnitine activate the mitochondria, thereby contributing to the improvement of NAFLD. PMID- 20571308 TI - [A case of large retroperitoneal lipoma mimicking liposarcoma]. AB - Lipomas are the most common benign tumors of adipose tissue among adults. Lipomas can occur almost anywhere in the trunk, extremities, mediastinum, and pelvis, but retroperitoneal lipomas are extremely rare. It should be distinguished from well differentiated liposarcoma in order to provide the appropriate treatment and follow up. We experienced a case of 60-year-old patient with large retroperitoneal lipoma mimicking liposarcoma causing palpable abdominal mass and pain. Abdominal computerized tomography (CT) showed 33 x 22 cm sized bulky fat containing mass with contrast enhanced solid portion in right retroperitoneum. Positron emission tomograpgy (PET) revealed increased 18F-FDG uptake at solid portion shown in abdominal CT. Imaging studies confirmed a high index of suspicion on liposarcoma. Laparotomy showed a large encapsulating tumor arising from retroperitoneum with fat necrosis. Pathologic examination of resected specimen revealed normal mature adipocytes without atypical cells, compatible with lipoma. PMID- 20571309 TI - [Hypertriglyceridemia-induced pancreatitis treated with insulin in a nondiabetic patient]. AB - Heparin and/or insulin stimulate lipoprotein lipase and are known to decrease serum triglyceride level. However, their efficacy in hypertriglyceridemia-induced acute pancreatitis in nondiabetic patients is not well documented. We report a case of hypertriglyceridemia-induced pancreatitis in 43-year-old nondiabetic woman in whom treatment with insulin was accompanied by reduction in serum triglyceride level and the resolution of pancreatitis. She presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. Her medical history was unremarkable. There was no history of alcohol consumption, and biliary imaging was not remarkable. Subsequent laboratory investigation revealed marked hypertriglyceridemia (1,951 mg/dL), impaired fasting glucose, and normal HbAlc level. The Ransons score and APATCH II score were 1 and 4. Abdominal CT showed diffuse enlargement of pancreas, peripancreatic fat infiltration, and multiple fluid collections around the pancreas. We treated the patient with the infusion of 5% dextrose and 1.5 unit/hr regular insulin to reduce serum triglyceride level. The level of serum triglyceride was decreased to 305 mg/dL on day 5. During the remainder of hospitalization, her clinical symptoms and laboratory values gradually improved. PMID- 20571311 TI - [Clinical characteristics of 17 cases of eosinophilic gastroenteritis]. PMID- 20571310 TI - [A case of cholangiocarcinoma suspected by continuous elevation of CA 19-9 after surgery of xanthogranulomatous cholecystitis]. AB - Xanthogranulomatous cholecystitis (XGC) is an unusual and destructive inflammatory process that is characterized by thickening of the gallbladder (GB) wall with a tendency to adhere to neighboring organs. XGC is often mistaken for GB carcinoma, and the frequency of the coexistence of these two lesions is approximately 10%. Therefore, in case of severe XGC, there is chance of either overlooking the carcinoma or other significant lesions. CA 19-9 is commonly measured in the serum of patients with hepatobiliary malignancies. Although CA 19 9 can be elevated in benign conditions such as cholestasis, pancreatitis, tuberculosis, thyroid disease etc., malignancy should be considered at first in setting of its significant and persistent elevation. We report a case of a 62 year-old man who showed continuously rising level of CA19-9 over 2000 U/mL after cholecystectomy for xanthogranulomatous cholecystitis and finally was diagnosed as cholangiocarcinoma by short-term follow up. PMID- 20571313 TI - Evaluation of a functional treatment for binge eating associated with bulimia nervosa. AB - Binge-eating disorders (BED) are a common problem affecting up to 5 percent of the American population in any given 6-month period. Currently, the most widely accepted treatment is some variation of Cognitive Behavior Therapy, although the abstinence rates following this type of treatment are only around 50%. A recent study by Bosch et al. explored the effects of extinction with four women who engaged in binge-eating behavior associated with BED and bulimia nervosa (BN). The treatment was successful, with three of the four participants obtaining abstinence. To date, this has been the only study examining this procedure. The purpose of the current study was to further evaluate extinction of binge eating with four young women who met diagnostic criteria for BN. The results showed that the treatment decreased binge eating to zero for all four women, although one dropped out of the study shortly after beginning the intervention. PMID- 20571314 TI - Body image distortion change during inpatient treatment of adolescent girls with restrictive anorexia nervosa. AB - Body image distortion is one core symptom of anorexia nervosa. However, little is known concerning its fluctuation over time. This paper pursues two objectives: (1) to assess body image distortion change during inpatient treatment of adolescent girls with restrictive anorexia nervosa (n=10), and (2) to identify associations between this change and the change observed to other measures of eating and weight-related disorders. A Quantification of Body Image Distortion computerized tool (Q-BID) and paper-and-pencil questionnaires were used at both beginning and end of inpatient treatment. Pearson correlations and linear regression analyses were conducted to identify associations between body image distortion change and the change observed to other measures of eating and weight related disorders. The results indicate that all adolescents experienced a body image distortion change. This change corresponds to a body image distortion decrease for 70% of them. The body image distortion change measure was highly correlated with the change observed in the score to the Eating Attitude Test (EAT 26) and to the Eating Disorder Examination Questionnaire (EDEQ-4) during the inpatient treatment. These two measures of change indeed explained 88.4% of the body image distortion change variance in the multivariate model. We concluded that the Q-BID is an interesting tool for the assessment of body image distortion change. More research is needed concerning the correlates of this outcome in order to elaborate appropriate interventions for both clinical and community settings. PMID- 20571315 TI - Pica in an eating disordered woman with multiple sclerosis: impulse dys-control, compulsive symptom or self-medication attempt? AB - We report about a complex case of pica in comorbidity with multiple sclerosis and binge eating disorder. Pica is classified among the feeding and eating disorders of infancy and early childhood, but there is a debate in the literature about the psychopathology and classification of this behavior. Some authors emphasize the similarities with the obsessive-compulsive spectrum disorders, whereas others propose an interpretation of pica as an addiction or as an impulsive behavior. The clinical case that we describe provides a picture of impulsive and compulsive features that are very difficult to disentangle. It is noteworthy that hypercalcemia is reported to have a protective/therapeutic effect against multiple sclerosis and seems to increase the plasmatic levels of beta-endorphins. The nature, diagnostic classification, and functions of pica are a topic worthy of future investigation. PMID- 20571316 TI - Eating disorders in men: current features and childhood factors. AB - BACKGROUND: Disturbed interactions with one's body and with other persons are two major features in eating disorders. This study was designed to assess current and childhood characteristics of eating-disordered men. METHODS: The authors interviewed 32 men with eating disorders (anorexia nervosa: N=9, bulimia nervosa: N=15, eating disorders not otherwise specified: N=8) and 43 control participants with no such history similar in age and educational status. The Structured Clinical Interview for DSM-IV was used to assess Axis I disorders and a self designed interview to assess actual social and sexual characteristics and childhood body-focused and social behaviors including sexual and physical abuse. RESULTS: The two groups differed significantly with regard to clinical, sexual and social features, with a three times higher rate of psychiatric disorders, fewer sexual and social relationships in the index group than in the controls. Eating-disordered men differed significantly from controls on most measures of body-focused and social behaviors, displaying higher rates of thumb sucking, nail biting, auto-aggressive behavior, and nudity as a familial taboo during childhood, as well as less parental bodily caressing than did controls. The index group reported significantly poorer relationships to their parents, fewer friends and persons of trust, and more often had adjustment problems at school than did their counterparts. CONCLUSIONS: Our data show that disturbed interactions with one's body and with other persons in eating-disordered men are associated with a body-denying and distant family climate and an auto-aggressive, anxious and inhibited social behavior during childhood. PMID- 20571317 TI - Rapid changes in night eating: considering mechanisms. AB - This paper considers possible mechanisms for the Night Eating Syndrome (NES). NES is a disorder characterized by a delay in the circadian rhythm of meals and of several neuroendocrine factors. The disorder occurs in genetically vulnerable people when exposed to stress. No convincing mechanism of the NES has been reported until now. To search for the mechanisms of NES, the long term treatment of two highly perceptive patients with rapid onset of the disorder are described. Disruption of three neuroendocrine systems compatible with these histories are discussed: the glucocorticoid system, the melanocortin [corrected] system, and the serotonergic system. Current evidence favors the serotonergic system and this view is strongly supported by the great effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the treatment of NES. PMID- 20571318 TI - Antecedents of eating disorders and muscle dysmorphia in a non-clinical sample. AB - Muscle Dysmorphia (MD) has recently been conceptualized as the male form of Eating Disorders (ED); although, it is not currently classified as an ED. The current study compares etiological models of MD symptomatology and ED symptomatology. It was hypothesized that sociocultural influences on appearance (SIA) would predict body dissatisfaction (BD), and that this relationship would be mediated by self-esteem (SE) and perfectionism (P); that BD would predict negative affect (NA); and that NA would predict MD and ED symptomatology. Two hundred-forty-seven female and 101 male college students at a midsouth university completed the study. All participants completed measures assessing each of the constructs, and multiple regression analyses were conducted to test each model's fit. In both models, most predictor paths were significant. These results suggest similarity in symptomatology and etiological models between ED and MD. PMID- 20571319 TI - Overweight and obesity among adults in Serbia: results from the National Health Survey. AB - INTRODUCTION: The purpose of the study was to evaluate the prevalence of overweight and obesity in Serbian adults. The impact of socioeconomic and lifestyle factors on weight was explored. MATERIALS AND METHODS: A cross sectional study representative of the adult population in Serbia was carried out in 2006. The study involved 13,796 people aged 20 years and over (6551 men and 7245 women). Individuals were interviewed and underwent anthropometric examination (overweight and obesity defined by body mass index--BMI). RESULTS: In 2006 in Serbia, 55.7% of adult population was overweight (19.0% of examinees were obese). Among men (body mass index >= 25 kg/m2) 26.4% considered themselves as above ideal weight (overweight and obese), while 70.9% classified themselves in an ideal body weight (normal weight). Among women (body mass index >= 25 kg/m2) 41.7% classified themselves as above ideal body weight while 56.0% as ideal body weight. Lower educational status, marriage status, rural area of settlement, third and fourth level of household income and irregular main meals were all strongly associated with overweight and obesity. CONCLUSIONS: High prevalence of overweight and obesity is a significant public health problem among Serbian adults. Efforts are needed to effectively promote daily physical activity and healthy eating through progressive modifications in lifestyle and the creation of supportive environments. PMID- 20571320 TI - Interaction between disinhibition and restraint: Implications for body weight and eating disturbance. AB - An increase in obesity is usually accompanied by an increase in eating disturbances. Susceptibility to these states may arise from different combinations of underlying traits: Three Factor Eating Questionnaire (TFEQ) Restraint and Disinhibition. Two studies were conducted to examine the interaction between these traits; one on-line study (n=351) and one laboratory based study (n=120). Participants completed a battery of questionnaires and provided self-report measures of body weight and physical activity. A combination of high Disinhibition and high Restraint was associated with a problematic eating behaviour profile (EAT-26), and a higher rate of smoking and alcohol consumption. A combination of high Disinhibition and low Restraint was associated with a higher susceptibility to weight gain and a higher sedentary behaviour. These data show that different combinations of Disinhibition and Restraint are associated with distinct weight and behaviour outcomes. PMID- 20571321 TI - Employee weight management through health coaching. AB - OBJECTIVE: This study will evaluate the effectiveness of an interactive health coaching intervention at lowering weight. METHODS: The study involved 5405 overweight or obese employees aged 18-85, who entered the program sometime during 2001-2008. RESULTS: Average body mass index (BMI) significantly decreased from 32.1 at baseline to 31.4 at 3 months, 31.0 at 6 months, and 30.6 at 12 months. Decreasing BMI was more pronounced in older age groups and among women, those using weight loss medication, those with higher BMI, and those with higher motivation and confidence to make behavior changes. When the effects of these variables on the decreasing trend in BMI were simultaneously estimated, only baseline classifications of BMI, health status, and confidence remained significant. Change in BMI through 12 months was -0.7% for those with normal weight, -2.0% for overweight, -3.6% for obese, and -7.1% for morbidly obese individuals at baseline. Among morbidly obese individuals, decrease in BMI through 12 months was -7.6% for those with "high" confidence to lose weight at baseline vs -4.4% for those with low confidence. Better health status at baseline was also related to more pronounced weight loss. CONCLUSION: Interactive health coaching significantly lowered BMI among participants through 3, 6, and 12 months of follow-up. PMID- 20571322 TI - Assessment of eating behaviour in young women requesting nutritional counselling and their mothers. AB - OBJECTIVE: The aim of this study was to explore the influence of maternal eating behaviour on a clinical population of young women compared with a non-clinical one. METHODS: A group of 59 young women (age 16-30 yr) attending a weight-loss Clinic and their mothers (n=59; age 37-64 yr) were enrolled. They were compared with a group of female students (n=59; age 18-36 yr) and their mothers (n=59; age 41-67 yr). Body weight and height were measured and body mass index (BMI) calculated. Eating behaviour was assessed by using the Eating Disorders Inventory (EDI), Eating Inventory (EI) and Eating Attitude Test 26 (EAT-26). RESULTS: The EDI-2 scales significantly different between the groups were drive for thinness, bulimia, body dissatisfaction, inadequacy, enteroceptive awareness and insecurity. The EI scales values were all different between the groups and consistently higher in the clinical populations. The differences between groups were even more striking for the EAT-26 scales; the clinical young women had the highest scores. The daughter-mother correlation for each scale in the clinical and non-clinical groups showed that the EDI-2 scales assessing eating behaviour, drive for thinness, bulimia and body dissatisfaction, were significantly related in the non clinical group but not in the clinical group. On the other side, the clinical group showed correlation for the scales assessing psychopathological traits such as perfectionism, interpersonal disrupt, enteroceptive awareness, impulsivity and insecurity. For EI scales the correlation was significant for disinhibition in the non clinical group. A correspondence was observed for dieting in the non clinical group and for food preoccupation in the clinical group. EDI-2, EI and EAT-26 scales assessing eating behaviour were strongly predictive of BMI in both groups. CONCLUSIONS: Maternal eating behaviour influences the young women; in particular mothers-daughters of the clinical group showed some problems, for which they still had to grow up and stand out. Finally, the control population revealed some eating disorders as well. PMID- 20571323 TI - Intellectual profile and level of IQ among a clinical group of obese children and adolescents. AB - This study explored intellectual profile of children attending a clinic for obesity and to what extent their characteristics predicted full scale IQ. Totally, 60 patients aged 8-16 years were recruited consecutively from the National Childhood Obesity Centre at Karolinska University Hospital in Sweden. These patients were tested using the Wechsler Intelligence Scale for Children (WISC). Of these 60 patients, 51 (85%) parents gave informed consent for their children's results to be included in this study (mean age 12.94, standard deviation, SD 2.42). The children's mean full scale IQ was 85.39. Parental education was strongly associated with child IQ. After adjustment for parental education, female gender and a higher level of obesity were associated with lower IQ. Obese children are at increased risk of having below average IQ and strategies to tackle associated problems should be developed in paediatric obesity clinics. PMID- 20571324 TI - Validity of self-reported body weight and height among women including patients with eating disorders. AB - The main objective of this study was to evaluate the accuracy of self-reported weight and height among women with eating disorders. The study sample consisted of 271 women aged 18-50 yrs: 73 anorexic patients (AN) with a body mass index (BMI) of <18.50 kg/m2, 54 normal weight bulimic or rehabilitated patients (BU/RE: 18.5 or =25 kg/m2) and 106 normal weight women without an eating disorder (NW: 18.510%, whereas p16 expression was scored as negative or positive. E2F1 expression cutoff values were tested for risk group variables as >5% and >10%. Correlation between the presence of necrosis, Ki-67 proliferation index, p16, E2F1 expression and the risk grade was determined by Spearman correlation test. Sensitivity and specificity were determined by Fisher exact test with P < or =0.05 considered as significant. High E2F1 expression (over 10%) and high Ki-67 proliferation index (over 10%) correlated significantly with increasing risk grade. There was also a significant correlation between the presence of necrosis and high-risk grade. No correlation was found between the risk grade and p16 expression. Our results suggest that in addition to high Ki-67 proliferation index, high E2F1 expression may also be a useful predictive marker for malignant potential of GISTs. PMID- 20571342 TI - P16 expression in squamous cell carcinomas of cervix and bladder. AB - CONTEXT/OBJECTIVE: p16 is a widely used immunohistochemical marker in gynecologic pathology. Strong and diffuse cytoplasmic and nuclear expression of p16 in squamous cell carcinomas (SCC) of the female genital tract is strongly associated with high-risk human papilloma virus infection and neoplasms of cervical origin. However, p16 can be expressed in other neoplasms and in several normal human tissues. Occasionally, SCCs may involve both uterine cervix and urinary bladder. Accurate identification of the site of origin in such cases has therapeutic and prognostic implications. We investigate the potential value of p16 expression in this distinction. DESIGN: We reviewed 74 SCCs, 38 (51%) from urinary bladder and 36 (49%) from uterine cervix obtained between 2003 and 2008. Of the 38 cases of bladder carcinoma, 21 occurred in females and 17 in males. Immunohistochemical analysis for p16 (DAKO M7247, clone 484, dilution of 1:50) expression was done in all cases using the labeled streptavidin-biotin method. RESULT: Strong and diffuse nuclear and cytoplasmic p16 positivity was observed in 45 cases (61%). Of the 38 SCCs of urinary bladder, 14 (37%) expressed p16 (8 males, 6 females). Of the 36 SCCs of uterine cervix, 31 (86%) were positive for p16. CONCLUSIONS: (1) The majority of SCCs of uterine cervix express p16. (2) More than a third of urinary bladder SCCs express p16. (3) SCCs of urinary bladder express p16 independent of gender. (4) p16 immunohistochemical expression alone cannot be used to discriminate between SCCs arising from uterine cervix versus urinary bladder. PMID- 20571343 TI - Increased detection of metastatic melanoma in pediatric sentinel lymph node biopsies using RT-PCR on paraffin-embedded tissue. AB - Sentinel lymph node (SLN) biopsy has become integral in the staging of patients with melanoma, and entails detailed histologic examination with immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase transcripts has been used to increase sensitivity but requires a dedicated piece of tissue that does not undergo histologic examination. We developed a nested RT-PCR assay for tyrosinase applicable on paraffin-embedded tissue and applied this to a series of SLNs from pediatric patients with melanoma. Thirty-six SLNs from 4 females and 4 males were included in the study. Eight lymph nodes with reactive changes were included as controls. SLNs were examined histologically and immunohistochemically for S100, tyrosinase, and MART1. Seven patients had between 1 and 4 morphologically-positive SLNs and one patient had negative SLNs (HISTO+; 12/36, 33%). Three lymph nodes were excluded from molecular analysis owing to inadequate RNA, and 29 of the remaining 33 nodes were positive (MOL+; 88%). All patients had at least 1 SLN positive by RT-PCR. Twelve were HISTO+/MOL+; 17 were HISTO-/MOL+; and 4 were HISTO-/MOL-. All control lymph nodes were negative for tyrosinase transcripts. The application of RT-PCR for tyrosinase to paraffin-embedded tissue significantly increased the number of positive SLNs and upstaged one patient from negative to positive. The prognostic implications of such findings require further investigation, especially in the pediatric age group. Nonetheless, this technique provides a useful tool to determine the clinical significance of RT-PCR positivity in melanoma SLNs. PMID- 20571344 TI - Primary cutaneous large B-cell lymphoma shows activation of nuclear factor kappa B and low incidence of Epstein-Barr virus. AB - Primary cutaneous lymphomas are defined as lymphomas, which are present in the skin without evidence of extracutaneous disease at the time of diagnosis. Primary cutaneous large B-cell lymphoma (PCLBCL) is a subtype of primary cutaneous B-cell lymphoma with a female predominance, occurring in elderly patients and known to have unfavorable prognosis. We evaluated 10 cases of PCLBCL in immunocompetent patients between 2005 and 2008. A panel of immunoperoxidase stains; CD3, CD10, CD20, BCL2, BCL6, and MUM1 were performed on all cases. Nuclear factor kappa B (NF-kappaB) pathway activation was evaluated using an immunostain for P65. The presence of Epstein-Barr virus (EBV) was assessed using Epstein-Barr virus encoded RNA (EBER) in situ hybridization probe. All cases were CD20 positive and CD3 negative. CD10, BCL6, BCL2, and MUM1 were positive in 4/10 (40%), 6/10 (60%), 7/10 (70%), and 7/10 (70%) cases, respectively. NF-kappaB activation was detected in 7/10 (70%) cases. One (10%) case was positive for EBV by in situ hybridization. Interestingly, the EBV positive case was also positive for MUM1 and negative for CD10, indicating an activated immunophenotype. In conclusion, majority of PCLBCL shows activation of NF-kappaB pathway with a low incidence of EBV. PMID- 20571345 TI - From hidroacanthoma simplex to poroid hidradenoma: clinicopathologic and immunohistochemic study of poroid neoplasms and reappraisal of their histogenesis. AB - BACKGROUND: Poroid neoplasms comprise classic poroma (P), hidroacanthoma simplex (HS), dermal duct tumor (DDT), and poroid hidradenoma (PH). The 3 latter are rarely reported. Poroid cells in P have recently been identified as keratinocytes of the lowermost acrosyringium and the sweat duct ridge. OBJECTIVES: To investigate a large cohort of poroid neoplasms to better define the clinical and pathologic aspects of HS, DDT, and PH. To analyze the expression of discriminatory keratins in all 4 poroid neoplasms. METHODS: 202 P, 11 HS, 17 DDT, 31 PH, and 5 composite tumors were examined under light microscopy, and 11, 9, 10, 15, and 2, respectively, by immunohistochemistry using anti-keratin antibodies, in particular, anti-K77, specific for luminal cells of the eccrine dermal sweat duct, and Ki-67 antibody. RESULTS: HS appeared later in life (66.6 years old) than P, DDT, and PH. Whereas P, DDT, and PH displayed unspecific clinical aspects, HS had most frequently the aspect of a large seborrheic keratosis with well-defined borders. HS, DDT, and PH were absent on palms and soles, but were found on the trunk, the lower limbs, and the upper limbs. Similar pathologic features were observed in all tumors, that is, a majority of poroid cells expressing K14, islands of K10-positive and K77-negative large cells. K77 expression was limited to luminal cells of intact ductal structures within the tumors. CONCLUSIONS: Our data demonstrate the common histogenesis of the 4 poroid neoplasms, which seem to derive from the basal keratinocytes of the sweat duct ridge and the lower acrosyringium. The variable length of the sweat duct ridge may account for the variety of poroid neoplasms, according to the site of tumor induction along this structure. PMID- 20571346 TI - Acral angioosteoma cutis. AB - Acral angioosteoma cutis is a benign lesion of unknown pathogenesis and is a newly described, distinct entity from other cutaneous lesions. It is clinically characterized by an exophytic lesion resembling pyogenic granuloma on the acral skin, combined with histologic findings of multiple tiny spicules composed of woven bone between well-formed capillaries proliferating in the superficial dermis. Here, we present a case of acral angioosteoma cutis on the left third toe of a 58-year-old woman, which was successfully treated by excision. PMID- 20571347 TI - Multiple desmoplastic cellular neurothekeomas localized to the face of a 16-year old boy. AB - Cellular neurothekeomas are relative uncommon benign dermal tumors of uncertain histogenesis. Most commonly they arise as a solitary papule or nodule on the head and neck or upper trunk of young adults with a slight female predominance. There has been only 1 previous report of multiple neurothekeomas. The patient described herein was a 16-year-old otherwise healthy boy who presented with approximately 30 facial papules that arose over the course of 6 months and progressively enlarged. Histologically, all lesions were composed of spindled to epithelioid cells, but varied in the degree of cellularity and dermal sclerosis. Immunohistochemical staining showed that the cells of interest expressed S100A6, vimentin, CD63 (NKI/C3), PGP 9.5, and factor XIIIa and were negative for CD68, glial fibrillary acid protein (GFAP), S-100, HMB-45, epithelial membrane antigen, actin, and CD57 consistent with a diagnosis of multiple desmoplastic cellular neurothekeomas. PMID- 20571348 TI - Cutaneous and systemic metastasis of a testicular choriocarcinoma. PMID- 20571349 TI - Review of and comments on article "Viral-associated nonmelanoma skin cancers: a review". PMID- 20571350 TI - Immunostaining for Treponema pallidum: caution in its evaluation. PMID- 20571351 TI - Calcium oxalate monohydrate crystals: a clue to ethylene glycol poisoning. PMID- 20571353 TI - Air in the urinary system. PMID- 20571352 TI - Managing type 2 diabetes in the primary care setting: beyond glucocentricity. AB - Successful management of type 2 diabetes mellitus (T2DM) requires attention to additional conditions often associated with hyperglycemia including overweight or obesity, dyslipidemia and hypertension, as each has some relationship with microvascular or macrovascular complications. Because control of cardiovascular risk factors is as important as glucose control in T2DM, these risk factors need to be addressed, and it is critical that antidiabetes medications do not exacerbate these risk factors. A patient-centered approach to treatment in which clinicians maximize patient involvement in the selection of antidiabetes therapy may lead to increased adherence and improved clinical outcomes. The incretin hormones, which include glucagon-like peptide-1 (GLP-1), are involved in glucoregulation and have become an important focus of T2DM research and treatment. Incretin-based therapies, such as the glucagon-like peptide-1 receptor agonists and the dipeptidyl peptidase-IV inhibitors, have shown beneficial effects on hyperglycemia, weight, blood pressure and lipids with a low incidence of hypoglycemia. PMID- 20571354 TI - XPC gene intron 11 C/A polymorphism is a predictive biomarker for the sensitivity to NP chemotherapy in patients with non-small cell lung cancer. AB - The fact that intron single nucleotide polymorphisms could regulate gene expression or even alter gene expression levels has been the focus of attention. To study the relationship between the intron 11 C/A single nucleotide polymorphism of XPC gene and the efficacy of vinorelbine and cisplatin (NP) chemotherapy, 164 patients with non-small cell lung cancer (NSCLC) taking NP chemotherapy drugs were evaluated according to the efficacy of the treatment. We used polymerase chain reaction restriction fragment length polymorphism to examine the C/A polymorphism in the XPC gene intron 11 of the DNA samples extracted from peripheral blood. It was found that the frequency of patients in the effective group with C/C+C/A genotype (37.6%) had significant difference to chemotherapy than that of patients with A/A homozygotes (27.7%) in the same group (P=0.043, odds ratio=2.366, 95% confidence interval=1.026-5.457). Therefore, NSCLC patients with the C/C+C/A genotype are more sensitive to NP treatment than those with the A/A genotype. The XPC gene intron 11 C/A polymorphism may be a predictive biomarker for sensitivity to NP chemotherapy in patients with NSCLC. PMID- 20571355 TI - Combined phase I/II study of imexon (AOP99.0001) for treatment of relapsed or refractory multiple myeloma. AB - Imexon [AOP99.0001 (4-imino-1,3-diazobicyclo[3. 1. 0]-hexan-2-one)] belongs to a novel class of promising anticancer agents that induce tumor apoptosis through oxidative stress. Clinical experience since the late 1960s has provided initial evidence for a clinical antitumor activity. Our open-label, multicenter phase I clinical trial was designed to further investigate the adverse event (AEs) profile and pharmacokinetics of AOP99.0001 in pretreated myeloma patients and collect initial data on the potential clinical efficacy in this indication. Thirty-six patients with relapsed or refractory myeloma, who had been pretreated with at least two lines of therapy earlier, were included. Imexon was applied intravenously on 5 consecutive days for 2 weeks (d1-5 and d8-12) for a 3-week cycle. The plasma half-life of AOP99.0001 and its active metabolite AOP99.0002 was found to be approximately 1.2 and 2.6 h, respectively. The mean duration of treatment with Imexon was 6.8 weeks in a dose range between 50 and 1000 mg/m without reaching dose-limiting toxicity. Drug-related AEs occurring with a frequency of greater than 10% were fatigue, nausea, constipation, headache, asthenia, anemia, thrombocytopenia, leukopenia and creatinine increase. A total of nine severe adverse events occurred in three patients. No mortality was encountered when patients were on treatment with Imexon. Preliminary antimyeloma efficacy of AOP99.0001 was observed with 1 minimal response, 12 (36%) stable disease responses, and all other evaluable patients had progressive disease. Remarkably, the patient with minimal response also experienced a complete clinical resolution of myeloma-associated polyneuropathy. Overall, Imexon was safe and well tolerated in the dose range investigated. Imexon showed minor clinical activity as a single agent in heavily pretreated myeloma patients. On account of its unique mechanism of action, favorable toxicity profile, initial clinical evidence for antimyeloma activity, and its known synergistic activity in combination with approved agents for myeloma treatment, AOP99.0001 is recommended for future clinical studies in combination regimens in multiple myeloma. PMID- 20571356 TI - Using database research to affect the science and art of medicine. PMID- 20571357 TI - Disentangling Hypnos from his poppies. PMID- 20571358 TI - Diagnostic medial branch blocks before lumbar radiofrequency zygapophysial (facet) joint denervation: benefit or burden? PMID- 20571359 TI - Feasibility and efficacy of preoperative epidural catheter placement for anterior scoliosis surgery. AB - BACKGROUND: Postoperative pain control via thoracic epidural catheters (TECs) is an important aspect of postoperative care, and ample evidence highlights its positive physiologic effects and superiority to intravenous analgesia. If epidural catheters for postoperative pain relief are used in scoliosis surgery, current practice is the intraoperative placement of the TEC by the surgeon because preoperative placement is considered challenging and dangerous. On the basis of magnetic resonance imaging of scoliotic spines, the authors developed a technique for preoperative placement of TEC and investigated its safety and feasibility. METHODS: Patients undergoing anterior scoliosis surgery were included, who received preoperative placement of TEC. Postoperative pain, problems associated with the TEC placement, possible side effects, radiographic data, and insertion levels of the TEC were noted. RESULTS: The apex vertebra was identified as a possible site for TEC placement due to dural sac shift leaving a wider epidural space on the convex side. Scoliosis-induced rotation of the vertebrae required realignment of the needle toward the convex side. Sixty patients were included. The success rate for TEC placement was 96.6%: one failed attempt, one catheter placed intrapleurally, and one patient with Horner syndrome. Seven percent of patients required additional rescue analgesia. All other patients had pain scores within acceptable limits (Visual Analogue Scale <5). CONCLUSIONS: The authors have demonstrated that it is possible to insert a TEC in patients with scoliotic spines with a high degree of success using a redesigned approach and thus provide adequate postoperative analgesia with a single epidural catheter. However, precautions have to be taken. PMID- 20571360 TI - Intraoperative systolic blood pressure variability predicts 30-day mortality in aortocoronary bypass surgery patients. AB - BACKGROUND: Few data support an association between blood pressure variability and clinical outcomes during cardiac surgery. We tested the hypothesis that intraoperative systolic blood pressure variability outside a targeted blood pressure range predicts 30-day mortality in patients undergoing cardiac surgery. METHODS: Electronically captured blood pressure data from 7,504 consecutive coronary bypass surgery procedures between September 1, 1996, and December 31, 2005, were divided into development and validation cohorts. Systolic blood pressure variability episodes outside a blood pressure range (e.g., higher than 135 or lower than 95 mmHg) were characterized by number of episodes, magnitude of episode, duration of episode, and magnitude x duration of excursion (i.e., area under the curve). Multiple logistic regression analysis was used to assess 30-day mortality association. The most predictive mortality risk characteristic and blood pressure range was tested in the validation cohort. RESULTS: A total of 3.1 million intraoperative blood pressure evaluations were analyzed. Systolic blood pressure variability was derived in 5,038 patients and validated in 2,466 patients (8% without cardiopulmonary bypass and 6% with valve procedure). Among all tested indices of blood pressure variability, mean duration of systolic excursion (outside a range of 105-130 mmHg) was most predictive of 30-day mortality (odds ratio = 1.03 per minute, 95% CI 1.02-1.39, P < 0.0001). CONCLUSIONS: Intraoperative blood pressure variability is associated with 30-day postoperative mortality in patients undergoing aortocoronary bypass surgery. PMID- 20571362 TI - Risk of obesity-related cancer after obesity surgery in a population-based cohort study. AB - OBJECTIVE: Obesity increases the risk of several cancers, but it is uncertain whether weight reduction is followed by any decreased risk. To address this topic, we selected a group of patients representing a substantial weight loss starting at a defined time, ie, patients submitted to obesity surgery. We hypothesized that risk of obesity-related cancer decreases with time after obesity surgery. SUMMARY BACKGROUND DATA: A nationwide, population-based cohort study of obesity surgery in 1980-2006 as registered in the Swedish Patient Register. New cancers were identified through the Swedish Cancer Register. Cohort members' observed total number of overall obesity-related cancers and groups of obesity-related cancer (breast, prostate, colorectal, endometrial, kidney) were divided by the expected numbers, representing the baseline risk, thus calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Time trends of SIR after obesity surgery were the main outcome measure. RESULTS: Among a total of 13,123 obesity surgery patients, contributing with 125,049 person years of follow-up, 296 new cases of obesity-related cancer were identified. There was no overall decrease in SIR of obesity-related cancer with increased time after obesity surgery (P for trend 0.40). Similarly, no statistically significant trends with follow-up time were found for cancer of the breast (P = 0.60), prostate (P = 0.34), endometrium (P = 0.83), or kidney (P = 0.42), while the risk of colorectal cancer increased with time (P for trend 0.01) after obesity surgery. CONCLUSIONS: The weight reduction following obesity surgery might not be entailed by a decreased risk of obesity-related cancer with increasing follow-up time as compared with the baseline risk. PMID- 20571363 TI - Postoperative sepsis in the United States. AB - OBJECTIVES: To evaluate the incidence of postoperative sepsis after elective procedures, to define surgical procedures with the greatest risk for developing sepsis, and to evaluate patient and hospital confounders. BACKGROUND DATA: The development of sepsis after elective surgical procedures imposes a significant clinical and resource utilization burden in the United States. We evaluated the development of sepsis after elective procedures in a nationally representative patient cohort and assessed the effect of sociodemographic and hospital characteristics on the development of postoperative sepsis. METHODS: The Nationwide inpatient sample was queried between 2002 and 2006 and patients developing sepsis after elective procedures were identified using the patient safety indicator "Postoperative Sepsis" (PSI-13). Case-mix adjusted rates were calculated by using a multivariate logistic regression model for sepsis risk and an indirect standardization method. RESULTS: A total of 6,512,921 weighted elective surgical cases met the inclusion criteria and 78,669 cases (1.21%) developed postoperative sepsis. Case-mix adjustment for age, race, gender, hospital bed size, hospital location, hospital teaching status, and patient income demonstrated esophageal, pancreatic, and gastric procedures represented the greatest risk for the development of postoperative sepsis. Thoracic, adrenal, and hepatic operations accounted for the greatest mortality rates if sepsis developed. Increasing age, Blacks, Hispanics, and men were more likely to develop sepsis. Decreased median household income, larger hospital bed size, urban hospital location, and nonteaching status were associated with greater rates of postoperative sepsis. CONCLUSIONS: The development of postoperative sepsis is multifactorial and procedures, most likely to develop sepsis, did not demonstrate the greatest mortality after sepsis developed. Factors associated with the development of sepsis included race, age, hospital size, hospital location, and patient income. Further evaluation of high-risk procedures, populations, and environments may assist in reducing this costly complication. PMID- 20571364 TI - High frequency of thoracic aneurysms in patients with abdominal aortic aneurysms. AB - OBJECTIVE: To investigate the prevalence of thoracic aortic aneurysms (TAA) in patients with abdominal aortic aneurysms (AAA). BACKGROUND: Different disease profiles between men and women treated for AAA have been reported. Reports regarding causes of death for treated AAA patients have shown an increased risk of death because of other aneurysms for women, possibly TAA. The prevalence of TAA in AAA patients is not well known. METHODS: Data for AAA patients attending the outpatient clinic at a university hospital were analyzed (N = 1055). Patients who had undergone abdominal and thoracic computed tomography were included (n = 354). The diameter of the aorta was measured in the ascending, descending, and infrerenal aorta. Comorbid conditions were analyzed. RESULTS: Mean age was 74 years, 23% were women. The presence of comorbid conditions did not differ between men and women except for a higher proportion of female smokers (P = 0.003). When sex-specific criteria were used, 100 patients (28%) had a TAA, 38 (48%) of the women compared with 62 (23%) of the men (P < 0.0001). Odds ratio for women compared with those of men to have a concurrent TAA was 3.09 (95% confidence interval, 1.84-5.22). CONCLUSIONS: More than one fourth of patients with AAA attending a regular outpatient clinic have a concomitant TAA, and women are particularly affected. During the last decades, the therapeutic options for TAA patients have changed considerably. Physicians need to increase the efforts to investigate also the thoracic aorta in AAA patients. PMID- 20571365 TI - Neurosteroid vitamin D system as a nontraditional drug target in neuropsychopharmacology. AB - Vitamin D is becoming increasingly recognized as a nontraditional drug target for different brain pathologies. Although widely known for their role in calcium metabolism, vitamin D and its receptor have been linked to several brain disorders, including cognitive decline, epilepsy, affective disorders, and schizophrenia. Here we discuss mounting evidence, and parallel recent clinical and animal behavioral, genetic and pharmacological data to emphasize the emerging role of the neurosteroid vitamin D system in brain function. PMID- 20571367 TI - Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. AB - There is growing interest on how to best tailor blood pressure (BP)-lowering medications according to the circadian (24 h) BP pattern of individual patients, that is, chronotherapy. Significant and clinically meaningful treatment-time differences in the beneficial and/or adverse effects of at least six different classes of hypertension medications are now known. Generally, calcium channel blockers are more effective with bedtime than morning dosing, and in the case of dihydropyridine derivatives bedtime dosing significantly reduces the risk of edema. Scheduling angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors at bedtime, as opposed to awakening, increases the proportion of patients with properly controlled BP, enhances the sleep-time relative BP decline towards a normal dipping pattern and best reduces urinary albumin excretion, a marker of functional renal status. The chronotherapy of conventional BP-lowering medications entails their correct scheduling with reference to the body's circadian rhythms, not only to achieve control of daytime and night-time systolic and diastolic BP but to normalize the dipping status of the 24 h pattern. Chronotherapy constitutes a cost-effective strategy for enhancing BP control during both nocturnal sleep and daytime activity and for potentially reducing the risk of cardiovascular disease and end-organ injury of the blood vessels and tissue of the heart, brain, kidney, eye and other organs. PMID- 20571370 TI - Improving health literacy: a Web application for evaluating text-to-speech engines. AB - The Internet is increasingly used as a medium for gathering and exchanging health information exchange. Healthcare professionals and organizations need to consider barriers that may exist within their patient-oriented Web applications. One approach to making the Web more accessible for those with lower health literacy may be to supplement textual content with audio annotation using text-to-speech engines, allowing for the creation of a virtual surrogate reader. One challenge is that with numerous text-to-speech engines on the market, objective measures of quality are difficult to obtain. To facilitate comparisons of text-to-speech engines, we developed an open-source Web application that measures user reaction times, subjective quality ratings, and accuracy in completing tasks across different audio files created by text-to-speech engines. Our research endeavor was successful in building and piloting this Web application; significant differences were found for subjective ratings of quality across three text-to speech engines priced at different levels. However, no significant differences were found with reaction times or accuracy between these text-to-speech engines. Future avenues of research include exploring more complex tasks, usability issues related to implementing text-to-speech features, and applied health promotion and education opportunities among vulnerable populations. PMID- 20571366 TI - Withdrawal from chronic exposure to amphetamine, but not nicotine, leads to an immediate and enduring deficit in motivated behavior without affecting social interaction in rats. AB - Psychostimulant withdrawal leads to depressive symptoms, such as anhedonia and social dysfunction. We determined the effects of withdrawal from chronic exposure to nicotine (9 mg/kg/day salt, 28 days) or amphetamine (10 mg/kg/day salt, 7 days) on the motivated response for a sucrose reward and on social interaction in rats. Both nicotine and amphetamine exposure increased the motivated response for sucrose. However, only spontaneous amphetamine withdrawal led to an immediate and persistent decrease in motivated behavior, which was not correlated with body weight loss. Social interaction was not affected during withdrawal from either drug. These results indicate that withdrawal from chronic amphetamine exposure leads to an immediate and enduring anhedonic state. PMID- 20571371 TI - Comparison of the quality and timeliness of vital signs data using three different data-entry devices. AB - It is important to evaluate the impact of clinical information systems on the quality and timeliness of documentation in the patient's record to ensure the systems are improving clinical care processes and providing value to the organization. An observational study was conducted to measure the accuracy and timeliness of vital signs data during three different stages of clinical documentation system implementation at a large academic medical center: (1) a paper medical record system, (2) a clinical documentation system with "computers on wheels" workstation outside the patient's room, and (3) a clinical documentation system with a Tablet PC affixed to the vital signs monitor. Patient observations (n = 270) were completed as patient care technicians made routine vital sign rounds. Equipping patient care technicians with a Tablet PC affixed to the vital signs monitor significantly improved (P < .05) the accuracy and timeliness of vital signs. In addition, a number of unintended consequences were discovered that proved helpful to the nurse managers and nursing informatics leadership team in providing support of the new system. Findings from this study emphasize the importance of ensuring that staff has the appropriate devices needed to effectively document patient care at the bedside. PMID- 20571373 TI - "I am not alone": a survey of women with peripartum cardiomyopathy and their participation in an online support group. AB - Peripartum cardiomyopathy is a devastating condition in which women without a previously identified heart condition experience heart failure in the ninth month of pregnancy or in the first 5 months after delivery of a baby. Online support groups are virtual communities for people affected by the same social or health issue. No literature exists on the benefits of women involved in an online support group for peripartum cardiomyopathy. The purpose of this descriptive study was to determine the benefits of participation in the online support group for peripartum cardiomyopathy based on a survey of active members of the group. All contacts between researchers and respondents were through e-mail. A survey of open-ended and Likert-type questions was used. Twelve women, aged 19 to 34 years, participated; all had a diagnosis of peripartum cardiomyopathy. This online support group is a vital resource for women with peripartum cardiomyopathy. Benefits to participation in the online support group included getting and sharing information, exchanging stories, being understood by other women, and gaining hope. Nurse practice implications include referring patients to reputable Web sites and support groups and serving as a professional facilitator in an online group. PMID- 20571374 TI - The outcomes of anxiety, confidence, and self-efficacy with Internet health information retrieval in older adults: a pilot study. AB - Technology has a great impact on nursing practice. With the increasing numbers of older Americans using computers and the Internet in recent years, nurses have the capability to deliver effective and efficient health education to their patients and the community. Based on the theoretical framework of Bandura's self-efficacy theory, the pilot project reported findings from a 5-week computer course on Internet health searches in older adults, 65 years or older, at a senior activity learning center. Twelve participants were recruited and randomized to either the intervention or the control group. Measures of computer anxiety, computer confidence, and computer self-efficacy scores were analyzed at baseline, at the end of the program, and 6 weeks after the completion of the program. Analysis was conducted with repeated-measures analysis of variance. Findings showed participants who attended a structured computer course on Internet health information retrieval reported lowered anxiety and increased confidence and self efficacy at the end of the 5-week program and 6 weeks after the completion of the program as compared with participants who were not in the program. The study demonstrated that a computer course can help reduce anxiety and increase confidence and self-efficacy in online health searches in older adults. PMID- 20571375 TI - Using clinical data to capture nurse workload: implications for staffing and safety. AB - The purpose of this project was to demonstrate how a hospital clinical database can be utilized to calculate individual nursing unit activities that affect nurses' workload. While research has established that staffing is associated with patient safety, few studies have examined ways to measure nurse workload and its impact on patient safety. The widely used midnight census does not account for the number of patients who occupy a bed in a 24-hour period. In this study, a hospital clinical data repository was used to calculate workload measures such as total treated patients, midnight census, and admission, discharges, and transfers, as well as a unit activity index. Unit activity indexes for intensive care and medical-surgical units were compared over time, by shift, day of week, and month. Admission, discharges, and transfers varied according to unit type. During 1994 to 2006, unit activity index increased. Fluctuations in unit activity index were noted according to shift, day of week, and month. Hospital clinical data repositories can be used to calculate workload measures, and these measures should be incorporated with other traditional measures in making staffing decisions. PMID- 20571376 TI - Supportive decision making at the point of care: refinement of a case-based reasoning application for use in nursing practice. AB - Variations in nursing care have been observed, affecting patient outcomes and quality of care. Case-based reasoners that benchmark for patient indicators can reduce variation through decision support. This study evaluated and validated a case-based reasoning application to establish benchmarks for nursing-sensitive patient outcomes of pain, fatigue, and toilet use, using patient characteristic variables for generating similar cases. Three graduate nursing students participated. Each ranked 25 patient cases using demographics of age, sex, diagnosis, and comorbidities against 10 patients from a database. Participant judgments of case similarity were compared with the case-based reasoning system. Feature weights for each indicator were adjusted to make the case-based reasoning system's similarity ranking correspond more closely to participant judgment. Small differences were noted between initial weights and weights generated from participants. For example, initial weight for comorbidities was 0.35, whereas weights generated by participants for pain, fatigue, and toilet use were 0.49, 0.42, and 0.48, respectively. For the same outcomes, the initial weight for sex was 0.15, but weights generated by the participants were 0.025, 0.002, and 0.000, respectively. Refinement of the case-based reasoning tool established valid benchmarks for patient outcomes in relation to participants and assisted in point of-care decision making. PMID- 20571377 TI - ANI emerging leaders program. PMID- 20571378 TI - ANIA-CARING 2010 annual conference re-evolution in nursing informatics. PMID- 20571379 TI - Pericentric inversion, inv(14)(p11.2q22.3), in a 9-month old with features of Goldenhar syndrome. AB - Goldenhar syndrome, also called hemifacial microsomia or oculo-auriculo-verterbal dysplasia (OAVS) (MIM 164210), is a birth defect involving the first and second branchial arch derivatives with an incidence of 1/5000. The variable phenotype includes mostly unilateral deformity of the external ear and small ipsilateral half of the face with epibulbar dermoid and vertebral anomalies. A genome-wide search in one family suggested linkage to a region of 10.7 cM on chromosome 14q32; however, no candidate genes have been identified. We report on a 9-month old with OAVS and a pericentric inversion of chromosome 14 which he inherited from his phenotypically normal mother. Fluorescence in-situ hybridization analysis with bacterial artificial chromosome clones from chromosome 14 showed the breakpoint on 14q maps distal to 14q21.2, thus confirming the cytogenetic breakpoints. In light of previous linkage studies mapping OAVS to 14q, we propose that the long arm breakpoint in our proband disrupted a potential candidate gene for OAVS resulting in his clinical phenotype. PMID- 20571380 TI - Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature. AB - OBJECTIVE: We present 3 new cases of psychotic symptoms in patients with adult attention-deficit/hyperactivity disorder while regularly treated with a stimulant therapy with methylphenidate. METHODS: Existing literature about this theme is reviewed, and potential mechanisms are discussed. RESULTS AND CONCLUSIONS: Medication with methylphenidate should be avoided in patients with vulnerability to schizophrenia and in drug addiction, but reported cases without these risk factors demonstrate that a careful and regular psychiatric monitoring is essential in all patients treated with methylphenidate. PMID- 20571361 TI - Perioperative hypothermia (33 degrees C) does not increase the occurrence of cardiovascular events in patients undergoing cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial. AB - BACKGROUND: Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. METHODS: The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. RESULTS: There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). CONCLUSION: In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events. PMID- 20571381 TI - Cochrane review summary for cancer nursing: influenza vaccination in children having chemotherapy for cancer. PMID- 20571383 TI - Current perspectives in inflammatory bowel disease: stress response and autophagy, host-microbe mutualism, immune duality and plasticity, and early versus late disease. PMID- 20571384 TI - A systems biology viewpoint on autophagy in health and disease. AB - PURPOSE OF REVIEW: The field of autophagy is rapidly expanding to encompass many important areas of cell biology, physiology and disease. Recent discoveries and tools allow the connection of the autophagy pathway to other cellular signals and processes, thus beginning a systematic approach to elucidation of autophagy components, functions and connections. RECENT FINDINGS: We outline recent discoveries illustrating the role of autophagy in Parkinson's disease, inflammatory bowel disease (IBD) and cancer. Recently important details of the mechanisms by which autophagy operates in these contexts have been elucidated. We illustrate how autophagy can be triggered by diverse stimuli and how cell fate is determined by the responses to many signals and stresses. We discuss the known links between autophagy and apoptosis and present a working model of the current interactions between autophagy components, apoptosis and cell cycle control at different stages of autophagic vesicle progression. SUMMARY: Autophagy represents not only an essential metabolic process, but a hub which responds to diverse stresses and signals to aid cell survival or control cell fate. There are currently many known links between autophagy and disease states, and the pace of discovery appears to be accelerating. Thus an understanding of autophagy is likely to be crucial to current and future approaches to therapy. Here we give a systems biology view of the autophagy field and how it is being connected to other pathways, such as apoptosis and responses to reactive oxygen damage. PMID- 20571385 TI - Pediatric inflammatory bowel diseases: coming of age. AB - PURPOSE OF REVIEW: Inflammatory bowel diseases (IBD) comprise a heterogeneous group of distinct intestinal disorders. Here, we discuss the concept of childhood onset IBD as separate disease forms within a larger multifactorial disease category. RECENT FINDINGS: There are excellent epidemiological data indicating that the incidence of pediatric IBD, mainly Crohn's disease, is still increasing over the last decades, with indicators of more extensive and more severe disease presentations in children compared to adults, also reflected by higher levels of humoral immune responses. Recent genetic scans allowed to identify particular susceptibility genes for pediatric IBD forms, such as IL27 or probably DcR3. Early postnatal onset forms of IBD might reflect monogenetic causes, as suggested with the finding of IL10 signaling defects that may define a new form of IBD. SUMMARY: There are good epidemiological, genetic and clinical data to distinguish different forms of IBD, particularly forms starting early in life. Profound insights in the molecular basis of immune dysregulation in IBD have been gained over the last few years. These recent discoveries will nourish and substantially stimulate the future search for precise cause(s) responsible for life-long intestinal inflammation and it will help to explain the still ongoing rise in incidence in childhood IBD. PMID- 20571386 TI - Preventive therapy in postoperative Crohn's disease. AB - PURPOSE OF REVIEW: Recurrence of Crohn's disease following surgical resection is common, but the optimal strategy to assess, prevent, and treat postoperative recurrence remains unclear. Recent developments in the prevention and management of postoperative recurrence have provided additional information. RECENT FINDINGS: Predictors of Crohn's disease recurrence after surgery include cigarette smoking, disease behavior, number of prior resections, family history, anastomotic type, and time to first surgery. Only penetrating disease behavior and continued cigarette smoking after surgery remain clear predictors of postoperative Crohn's disease recurrence. Ileocolonoscopy is the only modality to detect mucosal recurrence after surgery; however, surrogate markers of inflammation, specifically stool lactoferrin and calprotectin as well as small intestine contrast ultrasound, are promising. Due to the high rate of surgery for the treatment of complications of Crohn's disease, prevention of postoperative disease has received considerable attention. Recent studies of azathioprine/6 mercaptopurine, nitroimidazole antibiotics, and infliximab have broadened the spectrum of medication options postoperatively. SUMMARY: Smoking cessation and ileocolonoscopy for early detection of Crohn's disease recurrence should be part of any postoperative management strategy. The selection of medication and optimal time to initiate treatment after surgery is less certain. Postoperative immunomodulators and antitumor necrosis factor agents may prevent Crohn's disease in those at high risk for recurrence. Treatment of patients by predictors of recurrence and personalization of management based on genotypes/phenotypes will be the focus of future study. PMID- 20571387 TI - Endoscopic techniques for recognizing neoplasia in Barrett's esophagus: which should the clinician use? AB - PURPOSE OF REVIEW: The key to prevention and cure of esophageal adenocarcinoma is the detection and eradication of neoplasia in patients with Barrett's esophagus. Multiple tools and technologies are emerging for this purpose. RECENT FINDINGS: A detailed white light examination with high-resolution endoscopy and recognition of lesions is paramount. A variety of imaging modalities are being studied for the detection of neoplasia in Barrett's esophagus. Chromoendoscopy, narrow band imaging, and autofluorescence provide a way to target suspicious areas. Confocal endomicroscopy and optical coherence tomography are means to pinpoint imaging to obtain information about the tissue microarchitecture. SUMMARY: The key to detection of neoplasia is a careful white light examination with high-resolution endoscopy and recognition of lesion characteristics. Additional imaging modalities may enhance targeting of lesions or provide more information at a focused level. Many of these modalities have yet to be validated in prospective randomized, multicenter trials. PMID- 20571388 TI - Management of gastroesophageal reflux disease that does not respond well to proton pump inhibitors. AB - PURPOSE OF REVIEW: Patients with gastroesophageal reflux disease (GERD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. These therapy-resistant patients have become the new face of GERD in clinical practice in the last decade and presently pose a significant therapeutic challenge to the practicing physician. We reviewed newly accumulated information about the management of PPI failure that has been published over the past 2 years. RECENT FINDINGS: There are diverse mechanisms that contribute to the failure of PPI treatment in GERD patients and they are not limited to residual reflux. Some of the causes of PPI failure may coincide in the same patient. Upper endoscopy appears to have limited diagnostic value. In contrast, esophageal impedance with pH testing on therapy appears to provide the most insightful information about the subsequent management of these patients. Commonly, doubling the PPI dose or switching to another PPI will be offered to patients who failed PPI once daily. Failure of such therapeutic strategies is commonly followed by assessment for residual reflux. There is growing information about the potential value of compounds that can reduce transient lower esophageal sphincter relaxations. Esophageal pain modulators are commonly offered to patients with functional heartburn, although supportive clinical studies are still missing. SUMMARY: Management of refractory GERD patients remains an important clinical challenge. Recent studies have cemented the value of impedance-pH testing in pursuing proper treatment. Presently, the most promising therapeutic development for this patient population is transient lower esophageal sphincter relaxation reducers. PMID- 20571389 TI - Current Opinion in Gastroenterology. Current world literature. PMID- 20571391 TI - Reprogramming adult hematopoietic cells. AB - PURPOSE OF REVIEW: Recent advances in molecular biology research have culminated in development of technologies to generate pluripotent stem cells from somatic cells. In addition to skin fibroblasts, hematopoietic cells also have been shown to be amenable to reprogramming to pluripotency. The present review discusses the relevance of these findings to basic researches and regenerative medicine, and how researchers can take advantage of hematopoietic cell reprogramming technologies. RECENT FINDINGS: In 2006, Yamanaka and his colleagues published their amazing observation that murine somatic cells can be reprogrammed to the embryonic stem cell-like state simply by retroviral-mediated introduction of three or four defined factors. Soon after, human cells also were shown to be amenable to similar reprogramming. Generation of induced pluripotent cells from several types of hematopoietic cells of both murine and human origins now has been reported. SUMMARY: Reprogramming adult hematopoietic cells will provide opportunities to obtain valuable materials with minimum risk and burden to patients. Reprogrammed cells can be used in research to elucidate disease mechanisms and in drug or toxicity screening. In clinical settings, patient derived induced pluripotent stem cells may be used to generate mature functional cells for various therapies. PMID- 20571392 TI - Plexiform neurofibroma genesis: questions of Nf1 gene dose and hyperactive mast cells. AB - PURPOSE OF REVIEW: Tumorigenic cells can co-opt normal functions of nonmalignant hematopoietic cells, promoting tumor progression. Recent mouse and human studies indicate that mast cells underpin inflammation in the plexiform neurofibroma microenvironment of neurofibromatosis type 1. In this model, Nf1 homozygous deficient Schwann cells recruit hyperactive mast cells, promoting tumorigenesis. Here, we discuss the importance of Nf1 gene dosage, delineate hematopoietic contributions to the plexiform neurofibroma microenvironment, and highlight applications to human treatment. RECENT FINDINGS: Previous studies found that plexiform neurofibroma formation in a mouse model requires biallelic loss of Nf1 in Schwann cells and an Nf1 heterozygous cellular background. Now, transplantation and pharmacological experiments have indicated that tumor formation specifically requires Nf1 heterozygosity of c-kit-dependent bone marrow. SUMMARY: Neurofibromatosis type 1 results from autosomal dominant mutations of the NF1 tumor suppressor gene. Although unpredictable second-hit mutations in the remaining NF1 allele precede local manifestations such as tumor formation, human and mouse data indicate that NF1/Nf1 gene haploinsufficiency modulates cellular physiology and disease pathogeneses. In particular, Nf1 haplo insufficient mast cells demonstrate multiple gain-in-functions, and mast cells permeate neurofibroma tissue. Transplantation experiments have shown that these aberrant mast cells critically underpin the tumor microenvironment. Using these findings, clinicians have medically treated a patient with a debilitating plexiform neurofibroma. PMID- 20571394 TI - Placenta as a newly identified source of hematopoietic stem cells. AB - PURPOSE OF REVIEW: The lifelong stream of all blood cells originates from the pool of hematopoietic stem cells (HSCs) generated during embryogenesis. Given that the placenta has been recently unveiled as a major hematopoietic organ that supports HSC development, the purpose of this review is to present current advances in defining the origin and regulation of placental HSCs. RECENT FINDINGS: The mouse placenta has been shown to have the potential to generate multipotential myelo-lymphoid hematopoietic stem/progenitor cells de novo. The cellular origin of HSCs generated in the placenta and other sites has been tracked to the hemogenic endothelium by using novel genetic and imaging-based cell-tracing approaches. Transplantable, myelo-lymphoid hematopoietic stem/progenitor cells have also been recovered from the human placenta throughout gestation. SUMMARY: The discovery of the placenta as a major organ that generates HSCs and maintains them in an undifferentiated state provides a valuable model to further elucidate regulatory mechanisms governing HSC emergence and expansion during mouse and human development. Concurrent efforts to optimize protocols for placental banking and HSC harvesting may increase the therapeutic utility of the human placenta as a source of transplantable HSCs. PMID- 20571395 TI - Key players for T-cell regeneration. AB - PURPOSE OF REVIEW: The thymus provides a unique and essential microenvironment for T-cell precursors to develop into mature functionally competent T lymphocytes. Ageing causes architectural changes in the thymus resulting in a loss of thymic epithelial space required for thymopoiesis - a process known as thymic involution. Additionally, cytoablative regimens used to treat malignancies also destroy thymic architecture. The net result of both processes is diminished thymic output and function that may lead to impaired immunity. Thus, immunocompromised individuals would benefit from strategies aimed at enhancing T cell reconstitution. RECENT FINDINGS: Here we discuss strategies such as the use of sex steroid ablation, keratinocyte growth factor, interleukin-7, and in-vitro generated progenitor T cells as candidates for restoring T-cell immunity. Using various animal models of ageing or hematopoietic stem cell transplantation, these strategies have been shown to restore thymic architecture and cellularity, resulting in increased output and T-cell function in the periphery. SUMMARY: These candidate approaches are currently being tested in clinical trials, with preliminary evidence showing encouraging effects on T-cell reconstitution. Nevertheless, although these strategies show clear promise in animal models, and in early human trials, further data are needed to determine their efficacy in patients. PMID- 20571396 TI - Molecular signatures in the diagnosis and management of follicular lymphoma. AB - PURPOSE OF REVIEW: Although karyotypic events in follicular lymphoma and its transformation to aggressive lymphoma have been well described, the underlying genetic changes have until recently remained obscure. Both germline and acquired molecular events are now known to predict disease risk and outcome, respectively. Recent developments in these fields are covered within this review. RECENT FINDINGS: Identification of a region of germline predisposition on chromosome 6p together with pesticide influence on disease-related changes suggests specific risk factors for follicular lymphoma. The profiling of S(mu) and immunoglobulin heavy-chain locus (IgH-VH) mutations in follicular lymphoma and relapse/transformed samples suggests divergent evolution from a common progenitor, whereas modular expression profiling highlights the stem cell-like origin of disease. Furthermore, methylation profiling indicates a significant epigenetic influence on disease and novel gene mutations provide exciting new targets for investigation. SUMMARY: Recent insights into follicular lymphoma identify constitutional and environmental predisposition further unravelling the concept of a lymphoma-initiating cell and the acquired events defining this disease. The major challenge remains successful translation of these findings into routine clinical practice. PMID- 20571393 TI - Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. AB - PURPOSE OF REVIEW: The review will integrate current knowledge of transcriptional circuits whose dysregulation leads to autoimmunity, neutropenia and leukemia. RECENT FINDINGS: Growth factor independent-1 (Gfi1) is a transcriptional repressor with essential roles in controlling hematopoietic stem cell biology, myeloid and lymphoid differentiation and lymphocyte effector functions. Recent work has suggested that Gfi1 competes or collaborates with other transcription factors to modulate transcription programs and lineage decisions. SUMMARY: Gfi1 is central to several transcriptional circuits whose dysregulation leads to abnormal or malignant hematopoiesis. These functional relationships are conserved from Drosophila development. Such conserved pathways represent central oncogenic or 'gatekeeper' pathways that are pivotal to understanding the process of cellular transformation, and illustrate key targets for clinical intervention. PMID- 20571397 TI - Current world literature. PMID- 20571399 TI - Keeping divalent ions in their proper place. PMID- 20571400 TI - Estrogens and bone disease in chronic kidney disease: role of FGF23. AB - PURPOSE OF REVIEW: To describe the direct and indirect effects of estrogen on bone with special emphasis on the analysis of the recent findings related to the putative role of FGF23 in the estrogen-dependent parathyroid hormone (PTH) suppression. RECENT FINDINGS: Estrogens act directly on bone cells, downregulating osteoclast precursors and differentiation, increasing osteoclast apoptosis and stimulating osteoblast proliferation and differentiation. However, estrogens can also act indirectly on bone, modulating the calcium-phosphorus vitamin D-PTH axis. It has been recently demonstrated that estrogens suppress PTH synthesis and secretion in a dose-dependent manner and reduce serum calcitriol and phosphorus levels by an indirect mechanism. In-vivo and in-vitro experiments demonstrated that FGF23 positively correlated, also in a dose-dependent manner, with the dose of estrogens and with the observed changes in calcitriol and phosphorus. SUMMARY: These new findings support the importance of the indirect effects of estrogens on bone, suggesting a role for FGF23 in the regulation of PTH by estrogens. PMID- 20571401 TI - Sodium sensing in the interstitium and relationship to hypertension. AB - PURPOSE OF REVIEW: Internal environment regulation, particularly volume and osmoregulation, has been a fundamental concept important to physiologists and clinicians for almost two centuries. Na balance, intracellular K homeostasis, the crucial role of the Na,K-ATPase pump, osmotic forces, and the overriding effect of the kidney on maintaining homeostasis are notions that have been taught by many and accepted by most for over 50 years. Nevertheless, contradictory findings, problems with simplistic balance explanations, and the notion of salt sensitive and salt-resistant hypertension have been nagging headaches in the straightforward, two-compartment model of electrolyte balance. RECENT FINDINGS: Na can be accumulated without commensurate water retention in the interstitium of the skin, and this skin Na storage is paralleled by increased polymerization and sulfation of glycosaminoglycans in the Na reservoir. Subcutaneous tissue macrophages express the transcription factor tonicity enhancer binding protein in response to Na-mediated interstitial osmotic stress and thereby secrete vascular endothelial growth factor C, which stimulates lymphatic formation and endothelial nitric oxide synthase expression, suggesting that the immune system is a regulator of volume and blood pressure homeostasis. SUMMARY: Our findings do not abrogate the notion of pressure natriuresis and renal regulatory function. However, we do suggest that extracellular Na, volume and blood pressure homeostasis cannot be maintained without extrarenal regulatory mechanisms. PMID- 20571402 TI - Current world literature. PMID- 20571403 TI - Retinol supplementation and mesothelioma incidence in workers earlier exposed to blue asbestos (Crocidolite) at Wittenoom, Western Australia. AB - Owing to the high rates of malignant mesothelioma in workers exposed to crocidolite earlier at Wittenoom and evidence of protection against cancer by vitamin A, a population-based cancer prevention programme providing retinol supplements (25 000 IU/day) was commenced in 1990. The former workers at Wittenoom known to be alive and living in Western Australia in June 1990 constitute the study population. The participants were classified into two groups: those who received supplemental retinol (intervention group) and those who received none (comparison group). The relative rate of mesothelioma for those receiving retinol was estimated using Cox regression, adjusting for cumulative asbestos exposure and age at first exposure to asbestos. Nine hundred and twenty eight former Wittenoom workers received retinol at some stage of the programme, whereas 1471 workers never received retinol (comparison group). Those who received retinol were younger, had a greater exposure to asbestos and smoked less than the comparison group. There were 65 cases of mesothelioma in the retinol group and 88 in the comparison group. After adjustment, the hazard ratio was 0.99 (95% confidence interval=0.70-1.41). This result did not alter when the participants who received only retinol once or those who received beta-carotene earlier were excluded from the analysis. In conclusion, this study provides little support for possible preventive effects of retinol against mesothelioma in workers exposed to blue asbestos. PMID- 20571404 TI - Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular assist devices long-term postimplantation. AB - BACKGROUND: Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device (VAD) implantation. The benefits of exercise training in patients with VAD are unknown. DESIGN AND METHODS: Fifteen patients, aged 38.3 +/- 15.9 years, bridged to heart transplantation with left ventricular assist device or biventricular assist device were randomized at a ratio of 2 : 1 to a training group (TG, n = 10) or a control group (n = 5), 6.3 +/- 4 months after implantation. Both the groups were advised to walk 30-45 min/day. TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min, three to five times a week, combined with high-intensity inspiratory muscle training using a computer designed software to respiratory exhaustion, two to three times a week for 10 weeks. The patients were tested using cardiopulmonary exercise testing, 6-min walk test, spirometry and electronic pressure manometer for inspiratory muscle strength (Pimax) and endurance (sustained Pimax) measurement. Quality of life was assessed with the Minnesota Living with Heart Failure questionnaire. RESULTS: TG improved peak oxygen consumption (19.3 +/- 4.5 vs. 16.8 +/- 3.7 ml/kg per min, P = 0.008) and VO2 at ventilatory threshold (15.1 +/- 4.2 vs. 12 +/- 5.6 ml/kg per min, P = 0.01), whereas the ventilation/carbon dioxide slope decreased (35.9 +/- 5.6 vs. 40 +/- 6.5, P = 0.009). The 6-min walk test distance increased (527 +/- 76 vs. 462 +/- 88 m, P = 0.005) and quality of life was improved (38.2 +/- 11.6 vs. 48.9 +/- 12.8, P = 0.005), as well as Pimax (131.8 +/- 33 vs. 95.5 +/- 28cmH2O, P = 0.005), sustained Pimax (484 +/- 195 vs. 340 +/- 193cmH2O/s/103, P = 0.005), and inspiratory lung capacity (2.4 +/- 0.9 vs. 1.7 +/- 0.7 L, P = 0.008) were improved. No significant changes were noted in the control group. CONCLUSION: Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus, may have additional importance in cases of destination therapy. PMID- 20571405 TI - Maximal exercise, limb ischemia, and endothelial progenitor cells. AB - OBJECTIVES: The concept of neovascularization in response to tissue ischemia was recently extended by the finding of postnatal vasculogenesis through circulating endothelial progenitor cells (EPCs). The aim of this study was to assess the role of acute ischemia for EPC mobilization in patients with peripheral arterial occlusive disease (PAOD) and in healthy volunteers. METHODS: The number of circulating EPCs was analyzed by flow cytometry in PAOD patients (n = 23) with exercise-induced limb ischemia for up to 72 h after a maximal treadmill test and in healthy volunteers (n = 17) who underwent a 15-min suprasystolic occlusion of one lower extremity to induce limb ischemia. Plasma concentrations of vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor alpha, and granulocyte macrophage-colony stimulating factor were determined by ELISA. RESULTS: EPCs (CD 34 pos/KDRpos) increased significantly in both PAOD patients from 82 +/- 20 to 256 +/- 52 (P < 0.05) and healthy volunteers from 144 +/- 39 to 590 +/- 61 cells per 1 million events (P < 0.05) in response to induced ischemia, with a maximum after 24 h and returned to baseline within 72 h. The relative increase in EPC numbers was significantly lower in patients with PAOD as compared with healthy volunteers (P < 0.05). Plasma levels of vascular endothelial growth factor increased from 27.4 +/- 3.1 to 126.4 +/- 12 pg/ml in patients with PAOD (P < 0.05) and from 30.7 +/- 6.1 to 134.1 +/- 12.4 pg/ml in healthy volunteers (P < 0.05). CONCLUSION: Both patients with symptomatic PAOD and healthy volunteers respond to a single episode of limb ischemia with a time dependent increase in circulating EPCs. The increase of EPC numbers in response to ischemia is reduced when vascular disease is present, underlining the reduced vasculogenic potential of patients with PAOD. PMID- 20571406 TI - Regional differences in body fat distributions among people with comparable body mass index: a comparison across six German population-based surveys. AB - INTRODUCTION: The mortality of circulatory diseases of the German population varies considerably across regions. The comparison of the regional distributions of cardiovascular risk factors can provide clues to the reasons for cardiovascular mortality differences. The aim of this study was to determine whether indirect measures of fat distribution within subgroups of comparable body mass indices (BMIs) differ by region in Germany. METHODS: We included six German population-based epidemiological studies conducted between 1997 and 2006 that included a detailed assessment of anthropometric measures including overall 15 215 people aged 45-74 years. We calculated mean values of BMI, waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). We estimated mean regional differences of WC, HC, and WHR within narrow ranges of BMI. RESULTS: BMI distributions across the study populations were very similar. However, body fat distributions as measured by WC within subgroups of similar BMIs differed considerably across regions. For example, among people with a BMI of 24.0-25.9, estimated WCs were on average 3.4 and 6.7 cm higher among men and women in Saxony-Anhalt than among men and women in Bavaria, respectively. CONCLUSION: We provide evidence that the BMI distributions across six population based surveys in Germany are very similar and that body fat distributions among people with comparable BMIs show relevant regional differences. Our observed WC differences might contribute to regional cardiovascular disease risk differences in Germany. Our findings may trigger further similar analyses across European populations to explain large area variations of cardiovascular disease burden. PMID- 20571408 TI - Physician experience in addition to ACLS training does not significantly affect the outcome of prehospital cardiac arrest. AB - BACKGROUND: Little data exists on whether the physicians' skills in responding to cardiac arrest are fully developed after the advanced cardiac life support (ACLS) course, or if there is a significant improvement in their performance after an initial learning curve. OBJECTIVE: To estimate the effect of physician experience on the results of prehospital cardiac arrests. MATERIALS AND METHODS: Prospective data were collected on all prehospital resuscitative attempts in the area by ACLS trained ambulance physicians. RESULTS: Of 232 attempted cardiac resuscitations, 96 (41%) patients survived to hospital admission and 44 (19%) were discharged alive. A group of 39 physicians responded to from one up to 29 cases with a mean of four cases. Physicians responding to five or fewer cases had a trend to fewer patients surviving to admission compared with those responding to six or more (36 vs. 45%, P=0.31) but no difference was found on survival to discharge (19 vs. 20%, P=0.87). CONCLUSION: In this study, resuscitative experience of the physician did not have a significant effect on survival suggesting that experience does not significantly add to the current ACLS training in responding to ventricular fibrillation/ventricular tachycardia. More studies are needed. PMID- 20571409 TI - HIV transmission by stage of infection and pattern of sexual partnerships. AB - BACKGROUND: Most model analyses examining the role of primary HIV infection in the HIV epidemic ignore the fact that HIV is often transmitted through long-term, concurrent sexual partnerships. We sought to understand how duration and concurrency of sexual partnerships affect the role of transmissions during primary HIV infection. METHODS: We constructed a stochastic individual-based model of HIV transmission in a homogeneous population where partnerships form and dissolve. Using observed contagiousness by stage of HIV infection, the fraction of transmissions during primary HIV infection at equilibrium was examined across varying partnership durations and concurrencies. RESULTS: The fraction of transmissions during primary HIV infection has a U-shaped relationship with partnership duration. The fraction drops with increasing partnership duration for partnerships with shorter average duration but rises for partnerships with longer average duration. Partnership concurrency modifies this relationship. The fraction of transmissions during primary HIV infection increases with increasing partnership concurrency for partnerships with shorter average duration, but decreases for partnerships with longer average duration. CONCLUSIONS: Partnership patterns strongly influence the transmission of HIV and do so differentially by stage of infection. Dynamic partnerships need to be taken into account to make a robust inference on the role of different stages of HIV infection. PMID- 20571410 TI - The applicability of the short sensory profile for screening sensory processing disorders among Israeli children. AB - The objective of this study was to examine the applicability of the short sensory profile (SSP) for screening sensory processing disorders (SPDs) among typical children in Israel, and to evaluate the relationship between SPDs and socio demographic parameters. Participants were 395 Israeli children, aged 3 years to 10 years 11 months, with typical development. Parents of all children completed the SSP. Factor analysis found similarity between the Hebrew version of the SSP and the original SSP. About 15% of the children had SPD. Differences between age groups and sexes were found in several SSP sections. In conclusion,typical children may have SPD. The SSP may be appropriate for screening SPD among Israeli children.These results should be strengthened by additional studies conducted on children with typical development as well as children with disabilities in which sensory processing problems are involved. PMID- 20571411 TI - Comparison of the ICF core set for cardiopulmonary conditions in the acute hospital setting among different types of transplant patients. AB - To compare the functioning profiles of patients receiving different types of organ transplants using the International Classification of Functioning, Disability, and Health. The patients (n =102) were enrolled between days 5 and 10 after discharge following receipt of an organ transplant,and assessed for sociodemographic variables, the Functional Independence Measure and Barthel Index, and the International Classification of Functioning, Disability,and Health core set for cardiopulmonary conditions in the acute hospital, augmented with three additional categories.Analysis was conducted by grouping the patients as follows: (1) kidney transplants; (2) all other kinds of transplants. Functional Independence Measure/Barthel Index scores were significantly higher in group 1 compared with group 2. Prevalences of 30% or greater for any impairment were noted for seven b factors, one s factor,and one d factor in group 1, whereas the corresponding numbers for group 2 were 14, 2, and 8, respectively. When prevalences of 30% or greater were calculated for severe or total impairment for all factors, there were none for group 1, but six factors for group 2. For the six factors, the prevalence difference between the groups was significant in five after a full Bonferroni correction (P < 0.000002). The factors with the highest barriers were e110 (products or substances for personal consumption, 36%) and e120(products and technology for personal use in daily living,42%) in group 2 (both significant with P < 0.000001 when compared with the respective prevalences in group 1).Although exercise seems to be the most needed rehabilitation function for kidney transplant patients, other transplant patients will require considerably more rehabilitation intervention. PMID- 20571412 TI - Identification of clinical factors associated with resistance to antidepressants in bipolar depression: results from an European Multicentre Study. AB - This study is the first investigation to identify clinical factors associated with treatment resistance in bipolar depression (TRBD). TRBD is defined as failure to respond to at least two consecutive adequate antidepressant trials. The primary objective of this European Multicenter Study was to identify specific clinical and demographic factors associated with TRBD in a sample of bipolar patients treated for a major depressive episode. A total of 261 bipolar patients with major depressive episode were included in the analysis. Among them, 162 patients were considered as responders to treatment and the remaining 99 patients were considered as treatment resistant with a 17-item Hamilton Rating Scale for Depression Score remaining superior or equal to 17 after two consecutive adequate antidepressant trials. Cox regression analysis was used to examine the association between individual clinical variables and TRBD. We found four clinical variables to be significantly associated with TRBD: melancholia [P=0.01, odds ratio (OR)=2.4], comorbidity with social phobia (P=0.02, OR=2.3), current suicidal risk (P=0.02, OR=1.8) and severe intensity of current depressive episode (P=0.01, OR=1.8). Our findings identify four clinical variables associated with TRBD, which could be further investigated in controlled prospective trials. PMID- 20571413 TI - HIV testing at a VA Medical Center in a high prevalence area after VHA policy change: things are looking up. PMID- 20571414 TI - Successful immunologic and virologic outcomes in elderly HIV-infected patients. PMID- 20571415 TI - Traceability of 3 generations of nucleic acid amplification tests for quantitative HIV-1 RNA measurements to meet the WHO HIV-1 RNA International Standards. PMID- 20571416 TI - Hemodynamic effects of single-dose vardenafil in subjects receiving maraviroc. PMID- 20571417 TI - Introduction: Paving the way for biomedical HIV prevention interventions in youth. AB - The HIV epidemic among youth continues to grow at alarming proportions throughout the world. Efficacious and comprehensive biomedical prevention interventions are desperately needed for this vulnerable population if a reduction in global HIV incidence is to be achieved. To succeed at enrolling youth in studies of such modalities, communities whose youth will be participating must be highly engaged throughout the spectrum of research concept development to implementation and later translation into programs. In this process, there are numerous challenges, both intrinsic and extrinsic to the youth themselves. Intrinsic ones include developmental considerations in physiology, pharmacology, and behavior; extrinsic considerations are those in the community, ethical, legal, and regulatory arenas and those in designing clinical trials for youth to feasibly participate. We convened a consultative meeting to deliberate over these considerations among a variety of experts representing youth and their community, advocacy groups, academia, industry, regulators, and others in the federal government. Broad recommendations aimed at many stakeholders in the adolescent HIV prevention research agenda were made and were to improve the timely inclusion of youth in this research to ensure that prevention agents can be used safely by youth as soon as they become available to adults. PMID- 20571418 TI - Barriers to adolescents' participation in HIV biomedical prevention research. AB - OBJECTIVES: The inclusion of adolescents in HIV prevention clinical research has the potential to improve the current understanding of the safety and efficacy of biomedical prevention technologies in younger populations that are at increasing risk of HIV infection. However, there are significant individual, operational, and community-level barriers to engaging adolescents in clinical prevention trials. METHODS: This paper identifies and addresses individual, operational, and community-level barriers to adolescents' participation in HIV biomedical prevention research. RESULTS: Barriers identified and addressed in this paper include: (1) insufficient understanding of clinic prevention research, (2) self presentation bias, (3) issues surrounding parental consent, (4) access to clinical trials, (5) mistrust of research, and (6) stigma associated with participation in clinical trials. Examples of programs where adolescents have been successfully engaged in prevention research are highlighted and the lessons learned from these programs indicate that establishing collaborations with key stakeholders in the community are essential for conducting biomedical research with vulnerable populations, including adolescents. CONCLUSIONS: Given the importance of understanding adolescents' reactions, acceptability, and utilization of new biomedical prevention technologies it is imperative that researchers acknowledge and address these barriers to enhance adolescents' participation and retention in HIV biomedical prevention research. PMID- 20571419 TI - Ethical and regulatory considerations for the inclusion of adolescents in HIV biomedical prevention research. AB - Adolescents should be enrolled in ethically appropriate and scientifically rigorous HIV biomedical prevention research involving vaccines, pre-exposure prophylaxis, or microbicides. There is general agreement that children should only be enrolled in a clinical trial if the scientific objectives cannot be met either through enrolling adult subjects who can provide informed consent personally or through conducting research using animal models. In addition, the risks to which children are exposed in a clinical trial without the possibility of direct therapeutic benefit must be low. Children also should not be placed at a disadvantage after being enrolled in a clinical trial by, for example, being exposed to an unnecessarily risky intervention or by failing to receive a comparable treatment that would prevent significant morbidity or mortality. In light of this shared framework, we discuss the timing of enrolling adolescents in HIV prevention trials; some general study design considerations that may be necessary for adequate labeling of products for an adolescent indication; the use of data obtained from international studies for licensure applications in the United States; the role of parental permission and adolescent assent to research participation; and the inclusion of pregnant adolescents in HIV biomedical prevention research. PMID- 20571420 TI - Behavioral considerations for engaging youth in HIV clinical research. AB - From both scientific and ethical perspectives, it is important that youth be enrolled in biomedical HIV prevention clinical trials. At the same time, adolescents, as minors, are considered a vulnerable population requiring particular attention to the reduction of potential harm associated with participation in such trials. In this article, we review the evidence supporting enrollment of youth in HIV clinical trials, including data on HIV infection rates, sexual behavior, and cognitive, psychosocial, and neurophysiological development. Next, we address the potential risks associated with clinical trial participation, with a focus on the concept of preventive misconception, the tendencies to (1) overestimate the probability of assignment to the experimental condition, as opposed to the placebo, and (2) assume that the experimental intervention is efficacious. Finally, we discuss targeted interventions to reduce preventive misconception and the importance of developing and testing adolescent friendly risk-reduction interventions that are tailored to the structure and time frame of a biomedical HIV prevention clinical trial. The very issues that make inclusion of youth in HIV prevention clinical trials necessary also demand that particularly intensive efforts be made to protect participating minors from the harm that could accrue from a clinical trial. PMID- 20571422 TI - Involving vulnerable populations of youth in HIV prevention clinical research. AB - Adolescents continue to be at high risk for HIV infection, with young men who have sex with men and youth with drug abuse and/or mental health problems at particularly high risk. Multiple factors may interact to confer risk for these youth. Engaging vulnerable youth in HIV prevention research can present unique challenges in the areas of enrollment, retention, and trial adherence. Examples of successful engagement with vulnerable youth offer encouraging evidence for the feasibility of including these youth in clinical trials. Ethical challenges must be taken into consideration before embarking on biomedical HIV prevention studies with vulnerable youth, especially in the global context. Given the many individual and contextual factors that contribute to their high-risk status, it is essential that vulnerable youth populations be included in HIV prevention clinical research studies. PMID- 20571421 TI - Youth-specific considerations in the development of preexposure prophylaxis, microbicide, and vaccine research trials. AB - Preventing HIV infection in adolescents and young adults will require a multimodal targeted approach, including individual-directed behavioral risk reduction, community-level structural change, and biomedical interventions to prevent sexual transmission. Trials testing biomedical interventions to prevent HIV transmission will require special attention in this population due to the unique psychosocial and physiologic characteristics that differentiate them from older populations. For example, microbicide research will need to consider acceptability, dosing requirements, and coinfection rates that are unique to this population. Preexposure prophylaxis studies also will need to consider potential unique psychosocial issues such as sexual disinhibition and acceptability as well as unique pharmacokinetic parameters of antiretroviral agents. Vaccine trials also face unique issues with this population, including attitudes toward vaccines, risks related to false-positive HIV tests related to vaccine, and different immune responses based on more robust immunity. In this article, we will discuss issues around implementing each of these biomedical prevention modalities in trials among adolescents and young adults to help to guide future successful research targeting this population. PMID- 20571423 TI - Epidemiology of HIV infection and risk in adolescents and youth. AB - Adolescents and youth aged 15-24 are one of the populations most impacted by the global HIV epidemic with an estimated 50% of new infections occurring in this age group. They are thus one of the prime populations for targeting behavioral and biomedical preventions. However, the dynamics of the HIV epidemic in youth vary widely by geographic region and risk behavior profiles. There are also biological and neurodevelopmental considerations that must be considered in the development, testing, and ultimate dissemination of HIV prevention interventions. These concepts are broadly discussed here. PMID- 20571424 TI - A case study: lessons learned from human papillomavirus vaccine development: approval of a vaccine for use in children and young adolescents for prevention of an adult disease. AB - This article presents the adolescent clinical trials program for the quadrivalent HPV vaccine (Merck and Co, Inc, Whitehouse Station, NJ) as a case study of the development of a preventive intervention for use in young adolescents to protect against a future sexually transmitted infection and its associated diseases. In light of similarities in Human Papillomavirus (HPV) and HIV with regard to sexual transmission and the associated social and ethical issues related to prevention trial development, lessons learned from the approach taken to the inclusion of adolescents in the quadrivalent HPV vaccine program have potential relevance to future HIV prevention trials. Epidemiologic support for HPV vaccination in adolescents and a regulatory-approved approach to immunogenicity studies for bridging of efficacy from adults formed the basis for including young adolescents in the HPV program. The successful achievement of regulatory approval for use of this prophylactic intervention in young adolescents for prevention of a sexually transmitted infection that is most frequently not acquired before mid to late adolescence required understanding of the particular challenges of studying the vulnerable adolescent population with respect to issues such as federal regulations, the role of parents, confidentiality, empowerment, and retention, and awareness of the social and political context within which prevention interventions are introduced. PMID- 20571425 TI - Community engagement and investment in biomedical HIV prevention research for youth: rationale, challenges, and approaches. AB - There has been a growing awareness of the importance of engaging communities in the development, testing, and eventual dissemination of biomedical strategies. Community engagement offers many benefits but comes with many challenges. This article will discuss these benefits and challenges and describe two examples of community engagement, Connect to Protect in the United States, and the South African Studies on HIV in Adolescents Project in South Africa, that represent investment in community engagement as preparation for biomedical HIV prevention clinical trials for youth. PMID- 20571426 TI - Cardiovascular effects of a novel synthetic analogue of naturally occurring piperamides. AB - Cardiovascular responses to intravenous administration of a piperamide analogue, LASSBio 365, were investigated in anesthetized rats. LASSBio 365 [62.5-1000 microg/kg, intravenously (IV)] has potent cardiovascular effects that include hypotension and bradycardia, accompanied by a brief pressor effect and apnea. Bilateral vagotomy or atropine injection (2 mg/kg, IV) completely abolished the bradycardia. A drop in blood pressure was abolished in bivagotomized rats. However, it was only inhibited in atropine-treated rats. The apnea was inhibited by both treatments. The Bezold-Jarisch reflex (ie, hypotension, bradycardia, and apnea) induced by LASSBio 365 is altered neither by 5-HT3 antagonist (tropisetron, 0.1 mg/kg, intraarterially) nor by the P2x antagonist (PPADS, 8.6 mg/kg, IV). The pressor component was affected neither by any of these interventions nor by the 5-HT2 antagonist (ritanserin, 0.5 mg/kg, i.a.). In capsaicin-pretreated rats (50 mg/kg, subcutaneously), all responses evoked by LASSBio 365 were abolished, including the pressor effect, which was inhibited. The data show that LASSBio 365 evokes the Bezold-Jarish reflex, neither via serotonergic receptors nor purinergic receptors but perhaps via the vanilloid pathway. PMID- 20571427 TI - A novel highly selective adenosine A1 receptor agonist VCP28 reduces ischemia injury in a cardiac cell line and ischemia-reperfusion injury in isolated rat hearts at concentrations that do not affect heart rate. AB - The cardioprotective effects of a novel adenosine A1 receptor agonist N6-(2,2,5,5 tetramethylpyrrolidin-1-yloxyl-3-ylmethyl) adenosine (VCP28) were compared with the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) in a H9c2(2-1) cardiac cell line-simulated ischemia (SI) model (12 hours) and a global ischemia (30 minutes) and reperfusion (60 minutes) model in isolated rat heart model. H9c2(2-1) cells were treated with CPA and VCP28 at the start of ischemia for entire ischemic duration, whereas isolated rat hearts were treated at the onset of reperfusion for 15 minutes. In the H9c2(2-1) cells SI model, CPA and VCP28 (100 nM) significantly (P < 0.05, n = 5-6) reduced the proportion of nonviable cells (30.88% +/- 2.49% and 16.17% +/- 3.77% of SI group, respectively) and lactate dehydrogenase efflux. In isolated rat hearts, CPA and VCP28 significantly (n = 6-8, P < 0.05) improved post-ischemic contractility (dP/dt(max), 81.69% +/- 10.96%, 91.07% +/- 19.87% of baseline, respectively), left ventricular developed pressure, and end diastolic pressure and reduced infarct size. The adenosine A1 receptor antagonist abolished the cardioprotective effects of CPA and VCP28 in SI model and isolated rat hearts. In conclusion, the adenosine A1 receptor agonist VCP28 has equal cardioprotective effects to the prototype A1 agonist CPA at concentrations that have no effect on heart rate. PMID- 20571428 TI - Nebivolol lowers blood pressure and increases weight loss in patients with hypertension and diabetes in regard to age. AB - BACKGROUND: In patients with diabetes mellitus type 2 and arterial hypertension, the control of systolic and diastolic blood pressure is essential to reduce the risk of adverse events. The present study investigates the effect of treatment with the third-generation beta-blocker nebivolol, in female and male patients of different ages. METHODS: Five thousand thirty-one male and female patients with mild to moderate hypertension and type 2 diabetes were treated with a daily dose of 5-mg nebivolol for 12 weeks. Before and after therapy, each patient's blood pressure, heart rate, and body weight were measured and blood samples were obtained to study metabolic parameters. RESULTS: Nebivolol reduced systolic blood pressure, in both sexes, to a similar extent. In regard to age, the most significant reduction in blood pressure over the 12-week treatment period was observed in the group of patients below the age of 40. With advancing age, there was a decline in the reduction of systolic blood pressure induced by nebivolol. This effect was more evident among the decennial age groups in respect to diastolic blood pressure. In addition, we found weight reduction to be age dependent. Body weight was significantly more reduced in men compared with women. CONCLUSIONS: Nebivolol is effective in treating patients with diabetes suffering from high blood pressure and metabolic syndrome. The significantly decreased effect on blood pressure found in elderly patients may be attributed to increased endothelial dysfunction with advancing age. PMID- 20571430 TI - Dimethyl sulfoxide prevents 7beta-hydroxycholesterol-induced apoptosis by preserving lysosomes and mitochondria. AB - Dimethyl sulfoxide (DMSO) is a widely used vehicle for water-insoluble substances and exerts a wide range of pharmacologic effects including anti-inflammatory and free radical scavenging properties. Additionally, in an animal model, DMSO inhibited cholesterol-induced atherosclerosis. Despite such profound pharmacologic effects, mechanisms at the cellular level are not well understood. Atherogenic oxysterols, especially 7-oxysterols, are potent inducers of oxidative stress, cell apoptosis, and are elevated in human atherosclerotic lesions. In this study, we first investigated the effect of DMSO on 7beta-hydroxycholesterol induced apoptosis of U937 cells and then focused on its influences on production of reactive oxygen species, lysosomal, and mitochondrial membrane permeability. Our results revealed that DMSO protected U937 cells against 7beta hydroxycholesterol-induced cell death by preventing lysosomal and mitochondrial membrane permeabilization and reactive oxygen species production. Our results also emphasize the necessity for appropriate solvent control groups in experimental models in which DMSO has been used to examine drug effect or identify pathways. PMID- 20571429 TI - Heme-dependent and independent soluble guanylate cyclase activators and vasodilation. AB - Since the discovery of nitric oxide (NO), which is released from endothelial cells as the main mediator of vasodilation, its target, the soluble guanylyl cyclase (sGC), has become a focus of interest for the treatment of diseases associated with endothelial dysfunction. NO donors were developed to suppress NO deficiency; however, tolerance to organic nitrates was reported. Non-NO-based drugs targeting sGC were developed to overcome the problem of tolerance. In this review, we briefly describe the process of sGC activation by its main physiological activator NO and the advances in the development of drugs capable of activating sGC in a NO-independent manner. sGC stimulators, as some of these drugs are called, require the integrity of the reduced heme moiety of the prosthetic group within the sGC and therefore are called heme-dependent stimulators. Other drugs are able to activate sGC independent of heme moiety and are hence called heme-independent activators. Because pathologic conditions modulate sGC and oxidize the heme moiety, the heme-independent sGC activators could potentially become drugs of choice because of their higher affinity to the oxidized enzyme. However, these drugs are still undergoing clinical trials and are not available for clinical use. PMID- 20571431 TI - Late cardiac preconditioning by exercise in dogs is mediated by mitochondrial potassium channels. AB - We previously showed that exercise induces myocardial preconditioning in dogs and that early preconditioning is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels. We decided to study if late preconditioning by exercise is also mediated through these channels. Forty-eight dogs, surgically instrumented and trained to run daily, were randomly assigned to 4 groups: (1) Nonpreconditioned dogs: under anesthesia, the coronary artery was occluded during 1 hour and then reperfused during 4.5 hours. (2) Late preconditioned dogs: similar to group 1, but the dogs run on the treadmill for 5 periods of 5 minutes each, 24 hours before the coronary occlusion. (3) Late preconditioned dogs plus 5-hydroxydecanoate (5HD): similar to group 2, but 5HD was administered before the coronary occlusion. (4) Nonpreconditioned dogs plus 5HD: similar to group 1, but 5HD was administered before the coronary occlusion. Infarct size (percent of the risk region) decreased by effect of exercise by 56% (P < 0.05), and this effect was abolished with 5HD. 5HD by itself did not modify infarct size. Exercise did not induce myocardial ischemia, and the hemodynamics during ischemia-reperfusion period did not differ among groups. These effects were independent of changes in collateral flow to the ischemic region. We concluded that late cardiac preconditioning by exercise is mediated through mitochondrial adenosine triphosphate-sensitive potassium channels. PMID- 20571432 TI - Prevalence and impact of musculoskeletal comorbidities in cardiac rehabilitation. AB - BACKGROUND: With the demographic of patients entering cardiac rehabilitation (CR) indicating an older and more obese population, musculoskeletal comorbidities (MSKCS) may be escalating. METHODS: Musculoskeletal comorbidities affecting exercise were ascertained in 322 patients (233 men and 89 women) by a questionnaire and then an interview before and after 3 months of CR. Outcome variables were measured at baseline and 6 months. RESULTS: Musculoskeletal comorbidities perceived to affect exercise were reported by 50% of subjects at CR entry (48.1% of males, 55.1% of females; P = .26); most commonly occurring in the knee(s) (25%) and back (19%) due predominantly to arthritis (36.6%) and strains/sprains (28.6%). Multivariate regression revealed that greater body mass, older age, and lower peak oxygen uptake (VO2peak) were predictors of baseline MSKCs. At entry, patients with MSKCs were less likely to be exercising 30 minutes or more, 5 times per week than those without MSKCs (17.4% vs 28%, respectively, P = .03). Exercise modifications were required for 33.5% of patients with MSKC. By 3 months, 15.2% of patients developed 62 new MSKCs (26.5% strains/sprains). Six months of CR yielded significant (P < .001) and similar improvements in (VO2peak) for patients with and without baseline MSKCs (16.3% and 18.8%, respectively, P = .28). The improvement was mitigated in those with arthritic conditions compared with others (7.8% vs 20%, respectively, P = .01). By 6 months, 31.1% and 29.8% of patients with and without baseline MSKCs respectively, discontinued CR (P = .81). CONCLUSIONS: At entry to CR, patients reporting MSKCs had a poorer health profile than those without mskcs, including lower levels of physical activity and cardiovascular fitness, and unfavorable anthropometric measures. With exercise modifications, significant benefits were achievable without affecting compliance. PMID- 20571433 TI - Comparisons of the efficacy and tolerability of extended-release venlafaxine, mirtazapine, and paroxetine in treatment-resistant depression: a double-blind, randomized pilot study in a Chinese population. AB - To compare the efficacy and tolerability of antidepressants switch with extended release venlafaxine (venlafaxine-XR), mirtazapine, and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials. One hundred fifty adult patients with treatment-resistant depression according to their medical records and/or response to current treatments were randomly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d (n = 50), mirtazapine 45 mg/d (n = 55), or paroxetine 20 mg/d (n = 45) for 8 weeks. The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Secondary outcomes included the remission rate defined by the Self Rating Depression Scale of 50 or lower and the response rate defined by a 50% reduction or greater on the HRSD-17 total score, and the improvement of patients' general health functions. The completion rates were 82% for venlafaxine-XR, 81.8% for mirtazapine, and 82.2% for paroxetine. Only one patient in paroxetine arm discontinued the study owing to an adverse event. The remission rates based on the HRSD-17 were 42.0% for venlafaxine-XR, 36.4% for mirtazapine, and 46.7% for paroxetine. There were no statistical significances between treatment arms in remission rates. Similarly, there were also no significant differences between groups in secondary outcome measure. Venlafaxine-XR, mirtazapine, and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments. Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients. PMID- 20571435 TI - The Center for Clinical Computing Appreciation. PMID- 20571436 TI - Effects of a single 50% extra dose of methadone on heroin craving and mood in lower- versus higher-dose methadone patients. AB - Some patients on steady-state methadone occasionally crave for extra opioids for different reasons (eg, cue-elicited craving, stress). This study examined the acute-on-chronic effects on heroin craving, mood, and opioid-like symptoms of a single, extra half-dose on top of the patient's prescribed daily methadone dosage. A randomized, double-blind, placebo-controlled, counterbalanced crossover design was used to test the safety of this practice and the hypotheses that extra methadone would reduce heroin craving and improve mood, with greater responses in lower-dose (20-60 mg/d) as compared with higher-dose patients (80-120 mg/d). Fourteen stabilized methadone-maintained volunteers of each dose group were examined predrug and postdrug on 2 separate days using a range of self-report measures (Heroin Craving Questionnaire, visual analogs, Befindlichkeits-Skala, Short Opiate Withdrawal Scale, and Opioid Agonist Scale). Additionally, patients' expectations and guesses regarding treatment were assessed predrug and postdrug, respectively. No adverse effects occurred after extra methadone. Participants could not reliably distinguish between extra methadone and placebo. Repeated measures analyses of variance showed no effects of extra methadone on heroin craving and opioid agonist effects. However, extra methadone improved mood on the Befindlichkeits-Skala (F1/24 = 4.71, P = 0.04), with marginally greater effects in lower-dose patients ((F1/24 = 2.94, P = 0.099). A single 50% extra methadone dose is most likely safe in patients on stable methadone doses of 20 to 120 mg/d and may improve patients' mood. Extra methadone may constitute an important factor in the attractiveness of maintenance treatment and may enhance treatment outcome. PMID- 20571434 TI - The effect of aripiprazole on cue-induced brain activation and drinking parameters in alcoholics. AB - Because the effects of alcohol and its environmental cues on brain dopamine have been implicated in the maintenance of heavy drinking, drugs that modify dopamine might be useful in reducing drinking or promoting abstinence. The goal of the current study was to use an established brain imaging paradigm to explore the effect of aripiprazole (final dose 15 mg over a 14-day period), a dopamine stabilizer medication, on alcohol cue-induced brain activation and drinking in alcoholics. Non-treatment-seeking alcoholics were randomly assigned aripiprazole (n = 14) or identical placebo (n = 16) and reported their alcohol use while taking study medication for 14 days before an alcohol cue-induced brain functional magnetic resonance imaging study. In a Philips 3.0-T magnetic resonance imaging scanner, subjects were given a sip of alcohol before viewing a randomized presentation alcoholic- and nonalcoholic-beverage photographs while subjects rated their urge to drink. During photograph presentation, changes in regional brain activity were measured, and differences between viewing alcoholic beverage and nonalcoholic beverages were compared within and between groups. Brain activity analysis revealed increased activation for placebo-treated subjects in the right ventral striatum (P < 0.005; threshold 15 voxels), while there was a blunting of activation in this area in the aripiprazole-treated subjects. Aripiprazole-treated subjects, compared with placebo-treated subjects, also had significantly less heavy drinking during the 14-day medication period. The study provides both novel and valuable information regarding the effect of aripiprazole on cue-induced brain activation and voluntary drinking during treatment. PMID- 20571437 TI - A post hoc analysis of negative symptoms and psychosocial function in patients with schizophrenia: a 40-week randomized, double-blind study of ziprasidone versus haloperidol followed by a 3-year double-blind extension trial. AB - Schizophrenia is a persistent, lifelong illness such that enduring functional improvements may only occur over the course of years [corrected].This post hoc analysis in stable outpatients with schizophrenia investigated the negative symptom efficacy and treatment outcomes of ziprasidone (80-160 mg/d given twice a day, mean modal dose of 112 mg/d; and 80-120 mg/d given every day, mean modal dose of 96 mg/d) versus haloperidol (5-20 mg/d, mean modal dose of 12 mg/d) in a randomized, 40-week, double-blind study, followed by a double-blind continuation trial that extended up to 156 additional weeks. Symptomatic and functional recovery criteria were met when subjects attained both negative symptom remission and adequate psychosocial functioning based on the 4 Quality-of-Life subscales (instrumental role, interpersonal relations, participation in community, and intrapsychic foundations). Negative symptom remission (P = 0.005), as well as sustained adequate functioning (6 months) in instrumental role (P = 0.04) and participation in community (P = 0.02), was associated with significantly shorter time to remission in the ziprasidone 80 to 160 mg group than in the haloperidol group, as was the combination of symptomatic and functional recovery during the 196-week double-blind study period. A similar pattern was observed for the ziprasidone 80 to 120 mg group, which showed significant differences versus haloperidol in negative symptom remission and instrumental role functioning (but not other Quality-of-Life subscale measures). The clinically relevant outcome differences detected in this post hoc exploratory analysis support the potential for both enhanced remission in negative symptoms and psychosocial recovery during long-term treatment with an atypical agent and add to our understanding regarding the degree to which negative symptom remission can be attained in the maintenance phase. PMID- 20571438 TI - Both vascular endothelial growth factor and soluble Flt-1 are increased in type 2 diabetes but not in impaired fasting glucose. AB - OBJECTIVE: Inadequate vascular remodeling is contributory to increased cardiovascular events in people with type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG). Vascular endothelial growth factor (VEGF) and its regulatory molecule soluble Flt-1(sFlt-1) play important roles in atherogenesis. RESEARCH DESIGN: We measured fasting plasma concentrations of VEGF and sFlt-1 in 11 nondiabetic (ND) (aged 46.1 +/- 2.1 years; body mass index [BMI], 26.1 +/- 0.9 kg/m; glucose, 5.0 +/- 0.1 mM), 15 IFG (aged 52.9 +/- 1.8 years; BMI, 32.7 +/- 1.3 kg/m; glucose, 6.4 +/- 0.1 mM), and 8 DM (aged 55.8 +/- 3.2 years; BMI, 30.0 +/- 1.0 kg/m; glucose, 9.3 +/- 0.5 mM) subjects. RESULTS: Plasma VEGF (42.1 +/- 4.0 vs 24.2 +/- 0.9 vs 29.4 +/- 3.8 pg/mL, respectively) and sFlt-1 (119.4 +/- 4.9 vs 58.9 +/- 3.2 vs 56.7 +/- 1.2 pg/mL, respectively) concentrations were higher (P < 0.04) in DM than IFG and ND subjects. Whereas VEGF concentrations were significantly lower (P < 0.05) in IFG than in ND subjects, sFlt-1 concentrations did not differ between the IFG and ND subjects. CONCLUSIONS: Although plasma VEGF concentrations were higher (35%) in DM than in ND subjects, VEGF action on vascular remodeling was likely attenuated by higher sFlt-1 concentrations in DM. In contrast, IFG subjects did not have major perturbations in either VEGF or sFlt-1 levels. Further studies defining the roles of these mediators in DM and IFG are necessary to extend these observations. PMID- 20571439 TI - The highs and lows of maternal depression: cluster analysis of depression symptoms in a sample of African American women. AB - BACKGROUND: Maternal depression affects between 10% and 15% of US mothers. Emerging evidence suggests that variability in symptoms is linked to different risk factors and different pathological subtypes. Building on this research, this study examines manifestations of depression symptoms and risk factors associated with different manifestations among a socioeconomically heterogeneous sample of African American mothers. METHODS: Data were collected via telephone interviews with a community sample of 208 self-identified African American women with children 2 to 18 months old. Mothers were screened for depression symptoms using the Center for Epidemiological Studies Depression scale and reported on several psychosocial factors including social support, history of depression, and demographic characteristics. Cluster analysis was used to determine whether there were distinct subtypes of depression symptoms in this sample. RESULTS: A k-means cluster analysis of the 57 women with a positive depression symptom screen revealed 2 distinct groups characterized by higher versus lower symptom severity. A logistic regression indicated that mothers were more likely to fall into the high severity cluster if they were employed and reported lower levels of social support. LIMITATIONS: Because of its cross-sectional design, this study could not explore the timing and the course of depression symptoms, which may be more closely related to risk and functional impairment than the severity distinction found in this research. CONCLUSIONS: Researchers, pediatricians, and obstetricians working with African American mothers should screen for social support, with the understanding that those with low levels may be at increased risk for severe depression symptoms. Finally, the heterogeneity in symptoms suggests that clinicians should be aware of all depression symptoms among their patients rather than looking for specific, potentially stereotypical symptoms as cues. PMID- 20571440 TI - Carotid intima-media thickness and stiffness are independent risk factors for atherosclerotic diseases. AB - OBJECTIVE: We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases. METHODS: We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [beta], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events. RESULTS: Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI (P = 2.6 x 10) followed by bifurcation IMT (P = 5.5 x 10), and internal carotid artery IMT was least significant (P = 0.02). For stiffness, beta was most significant (P = 3.6 x 10) for stroke and MI, followed by elastic modulus (P = 1.1 x 10) and pulse wave velocity (P = 6.8 x 10). The best model for the combined effect was from beta (P < 0.03) and CCA (P = 0.056) or bifurcation IMT (P = 0.057). CONCLUSIONS: Carotid IMT and stiffness represent different properties of atherosclerotic vessel wall. Measuring both traits provides a better characterization of atherosclerosis. PMID- 20571441 TI - AIDS awareness and condom use among patients in a high-HIV-prevalence area in rural northern Anhui, China. AB - The objective was to assess AIDS awareness and condom use in a rural northern Anhui area with a high HIV prevalence. One hundred two AIDS patients underwent a structured interview using a standard questionnaire. There were 51 female and 51 male patients, whose mean age was 46.27 +/- 7.27 years and who had good knowledge of AIDS-related issues. More sexually active patients than those nonactive ones knew it more properly that AIDS was a blood-borne disease (100% vs 94.4%; P = 0.03). Significantly more female patients than male (62.7% vs 47.1%; P = 0.047) knew AIDS is incurable. Self-perceived risk was low, and only 84 respondents regarded the condom use as a common problem in their area. Two independent factors associated with a higher rate of condom use were the AIDS patients' income level and their knowledge about condom use. There was statistically significance between the patients who regularly obtained free condoms and those who did not. The patients who bought condoms on their own initiative had a higher chance of using condoms than those who did not. In conclusion, despite a high level of awareness of HIV/AIDS issues, self-perceived risk was low, condom use was infrequent, and especially men continued to have multiple sexual partners. PMID- 20571442 TI - Letter in response to the article "Optimum timing of blood tests for monitoring patients with Clostridium difficile-associated diarrhea" (J Investig Med.2010;58[4]:621-624). PMID- 20571443 TI - Effects of 14-week swimming training program on the psychological, hormonal, and physiological parameters of elite women athletes. AB - The purpose of the study was to investigate the influence of a 14-week swimming training program on psychological, hormonal, and performance parameters of elite women swimmers. Ten Olympic and international-level elite women swimmers were evaluated 4 times along the experiment (i.e., in T1, T2, T3, and T4). On the first day at 8:00 am, before the blood collecting at rest for the determination of hormonal parameters, the athletes had their psychological parameters assessed by the profile of mood-state questionnaire. At 3:00 am, the swimmers had their anaerobic threshold assessed. On the second day at 3:00 am, the athletes had their alactic anaerobic performance measured. Vigor score and testosterone levels were lower (p <= 0.05) in T4 compared with T3. In addition, the rate between the peak blood lactate concentration and the median velocity obtained in the alactic anaerobic performance test increased in T4 compared with T3 (p <= 0.05). For practical applications, the swimming coaches should not use a tapering with the present characteristics to avoid unexpected results. PMID- 20571444 TI - Differential correlations between anthropometry, training volume, and performance in male and female Ironman triathletes. AB - We investigated in 27 male Ironman triathletes aged 30.3 (9.1) years, with 77.7- (9.8) kg body mass, 1.78- (0.06) m body height, 24.3- (2.2) kg.m-2 body mass index (BMI), and 14.4 (4.8) % body fat and in 16 female Ironman triathletes aged 36.6 (7.0) years, with 59.7- (6.1) kg body mass, 1.66- (0.06) m body height, 21.5 (1.0) kg.m-2 BMI, and 22.8 (4.8) % body fat to ascertain whether anthropometric or training variables were related to total race time. The male athletes were training 14.8 (3.2) h.wk-1 with a speed of 2.7 (0.6) km.h-1 in swimming, 27.3 (3.0) in cycling, and 10.6 (1.4) in running. The female athletes trained for 13.9 (3.4) h.wk-1 at 2.1 (0.8) km.h-1h in swimming, 23.7 (7.6) km.h-1 in cycling, and 9.0 (3.7) km.h-1 in running, respectively. For male athletes, percent body fat was highly significantly (r2 = 0.583; p < 0.001) associated with total race time. In female triathletes, training volume showed a relationship to total race time (r2 = 0.466; p < 0.01). Percent body fat was unrelated to training volume for both men (r2 = 0.001; p > 0.05) and women (r2 = 0.007; p > 0.05). We conclude that percent body fat showed a relationship to total race time in male triathletes, and training volume showed an association with total race time in female triathletes. Presumably, the relationship between percent body fat, training volume, and race performance is genetically determined. PMID- 20571445 TI - Bilateral asymmetry in joint torque during squat exercise performed by long jumpers. AB - This study aimed to examine the bilateral differences in movement and joint torques during the squat exercise by using kinematic and kinetic analyses. Eighteen long jumpers participated in this study. They performed 3 repetitions of the squat exercise with loads of 50, 70, and 90% of their 3 repetition maximum (3RM). During the exercise, their movement was recorded using a Vicon motion capture system. Ground reaction forces (GRFs) were simultaneously measured by 2 force platforms, one under each foot. On the basis of these position and force data, joint angles and torques for the hip, knee, and ankle were calculated using inverse dynamics. Results showed that the peak vertical and horizontal GRFs did not differ between the takeoff and non-takeoff legs in any loading condition. However, the maximal flexion angle and peak torque at hip showed significant differences between the limbs under all loading conditions (p < 0.05). In addition, the peak ankle torque in the takeoff leg was larger than that in the non-takeoff leg under a load of 90% of 3RM. These results indicate that joint torques may be bilaterally asymmetric when long jumpers perform the squat exercise, which should be considered when attempting to decrease the risk of injury. PMID- 20571446 TI - Isolated and combined effects of aerobic and strength exercise on post-exercise blood pressure and cardiac vagal reactivation in normotensive men. AB - The purpose of this study was to examine blood pressure (BP), heart rate (HR), and cardiac vagal reactivation (VR) after an aerobic training session (ATS), a strength training session (STS), and a combined aerobic and strength training session (ASTS) in normotensive men. Eleven healthy men (age 26.8 +/- 2.9 years, body mass index 24.3 +/- 1.6 kg.m) with at least 6 months of strength and aerobic training experience performed an STS, an ATS, and an ASTS in a counterbalanced crossover design. Blood pressure and HR were measured at rest and at 15-minute intervals post-training for 1 hour. Vagal reactivation was measured during the first minute immediately post-exercise. After STS and ASTS, systolic BP (SBP) and mean arterial BP (MAP) remained significantly lower than at rest at all time intervals (p < 0.05). After ATS, SBP was significantly lower than at rest at 30 minutes and beyond (p < 0.01); however, no significant differences were observed for MAP. Post-training HR remained high after STS and ASTS at all intervals (p < 0.01). However, after ATS, the HR remained high only at the 15-minute post exercise interval (p < 0.01). Vagal reactivation was significantly less pronounced after the first 30 seconds post-exercise (p < 0.01) in ASTS (531.3 +/- 329.6 seconds) than in ATS (220.7 +/- 88.5 seconds) and in STS (317.6 +/- 158.5 seconds). The delta of the HR decrease at 60 seconds post-exercise was greater (p < 0.00) in ATS (33.4 +/- 12.7 b.min) than in STS (14.1 +/- 7.2 b.min) and in ASTS (11.4 +/- 7.1 b.min). In conclusion, post-exercise BP reduction was independent of the type of exercise; however, HR remained significantly greater after combination of strength and aerobic exercise, implying a reduction in cardiac VR after this type of training. Therefore, strength and conditioning professionals may prescribe aerobic, strength, or a combination of aerobic and strength exercise to assist individuals concerned with BP control, thus allowing for variety in training while similarly impacting post-exercise SBP regardless of desired exercise modality. PMID- 20571447 TI - Power output in the jump squat in adolescent male athletes. AB - The load that maximizes power output in the jump squat (JS) in college-aged athletic males has been reported to be 0% of 1 repetition maximum [1RM] squat strength) or in other words body mass. No data exist concerning adolescent athletic males. In addition, strength levels have been theorized to possibly affect the load that maximizes power output in the JS. The purpose of this investigation was to identify the load that maximizes power output in the JS in adolescent athletic men, and concurrently describe their strength level and its effect on the load that maximizes power output. Eleven high-school male athletes were tested on 2 occasions, first determining their 1RM in the squat (1RM = 141.14 +/- 28.08 kg; squat 1RM-to-body mass ratio = 1.76 +/- 0.15) and then performing JS testing at loads equal to 0% (body mass), 20, 40, 60, and 80% of squat 1RM. Peak power (PP), peak force, peak velocity (PV), and peak displacement were measured at each load. Jump squat at the 0% load produced significantly (p <= 0.05) higher PP, PV, and peak displacement in comparison with the 40, 60, and 80% loading conditions. It was concluded that the load that maximizes power output in the JS is 0% of 1RM in adolescent athletic men, the same as found in college-aged athletic men. In addition, strength level relative to body mass did not affect the load that maximized power output. Practically, when devising a training program to increase PP, it is important to include JSs at body mass along with traditional strength training at heavier loads to increase power output across the entire loading spectrum. PMID- 20571448 TI - Pulsed acoustic cellular treatment induces expression of proangiogenic factors and chemokines in muscle flaps. AB - BACKGROUND: Pulsed Acoustic Cellular Expression (PACE) treatment is a novel technology with potential to improve tissue perfusion, but the mechanism of this action is unknown. We assessed in vivo the effect of PACE therapy on muscle microcirculatory hemodynamics, neovascularization, and proangiogenic and proinflammatory gene expression. METHODS: Cremaster muscles were prepared for standard intravital microscopy in 42 Lewis rats divided into five groups: (1) control (n = 10); acute PACE treatment 15 minutes before surgery with (2) 200 impulses (n = 8) and (3) 500 impulses (n = 8); and PACE treatment 24 hours before surgery with (4) 200 impulses (n = 8) and (5) 500 impulses (n = 8).Microcirculatory hemodynamics of red blood cell velocity and capillary perfusion were recorded for 4 hours. Gene expression levels of proinflammatory (inductible nitric oxide synthase [iNOS]) and proangiogenic factors (endothelial nitric oxide synthase [eNOS], vascular endothelial growth factor [VEGF], chemokine (C-X-C motif) ligand 5 [CXCL5], chemokine (C-C motif) ligand 2 [CCL2], and chemokine (C-C motif) receptor 2 [CCR2] were measured using Taqman real-time Polymerase Chain Reaction (PCR). Immunohistochemistry assessed expression of proangiogenic factors: VEGF, von Willebrand factor (vWF), and vessel density by CD31. RESULTS: PACE treatment resulted in an increase of arteriolar diameters in acute groups 2 and 3 (p < 0.05). In group 5, vessel densities assessed by CD31, VEGF, and vWF expression increased significantly 24 hours after PACE treatment compared with control (p < 0.05). PACE application downregulated proinflammatory iNOS gene expression and upregulated proangiogenic genes expression of eNOS, VEGF, CXCL5, and CCL2. CONCLUSIONS: Application of PACE treatment, applied as short time acting preconditioning and conditioning treatment, resulted in upregulation of proangiogenic chemokines gene expression in the muscle and showed upregulation of expression of proangiogenic factors such as VEGF and vWF on the vessel endothelium. PMID- 20571449 TI - Analysis of foot and ankle kinematics after operative reduction of high-grade intra-articular fractures of the calcaneus. AB - BACKGROUND: High-grade calcaneal fractures represent a complex injury, with limited data to support the advisability of open reduction. Restoration of foot and ankle kinematics during walking, which has been previously shown to be significantly limited after nonoperative treatment, has never been studied after the operation. This study was designed to address this lack of information to assess the advisability of the operation in this respect. METHODS: Twenty patients with a minimum of 2 years after Open Reduction Internal Fixation (ORIF) for high-grade fractures were evaluated with a computerized gait analysis system, in addition to the radiographic assessment and functional questionnaires. Foot and ankle kinematic variables in the operated limbs were compared with contralateral limbs and with matched healthy control individuals. RESULTS: The kinematical gait analysis demonstrated recreation of normal ankle motions in operated patients. Subtalar motion demonstrated relative symmetry between operated and contralateral limbs, but it was still significantly limited compared with healthy controls. Bohler angle was between 15 degrees and 35 degrees . Functional questionnaires and rate of postoperative complications supported the generalizability of our operated group compared with previous literature assessing similar injuries. CONCLUSIONS: In high-grade calcaneal fractures, when recreation of gross calcaneal anatomy is obtained during the operation, walking ankle motion is recreated as well. However, subtalar motions, although recreated to a certain extent, still demonstrate limitations when compared with noninjured individuals. These results support the advisability of the operation in these complex injuries, but they demonstrate that subtalar motion is not completely normalized despite a favorable anatomic outcome. PMID- 20571450 TI - Investigation of the relationship between venticular fibrillation duration and cardiac/neurological damage in a rabbit model of electrically induced arrhythmia. AB - BACKGROUND: To establish a simple, economic, and reliable alternating current (AC)-induced cardiac arrest (ACCA) model in rabbits for cardiopulmonary cerebral resuscitation research. METHODS: Ventricular fibrillation was induced in 27 New Zealand rabbits by external transthoracic AC, which were randomly divided into three groups according to the duration of untreated ACCA (ACCA-3 minutes, ACCA-5 minutes, and ACCA-8 minutes). After ACCA, all animals received cardiopulmonary resuscitation for 2 minutes and subsequent defibrillation until return of spontaneous circulation (ROSC). The troponin I levels were measured at 4 hours after ROSC. Animals died spontaneously or were killed at 72 hours after ROSC. The hippocampus were removed and fixed in 3% formalin. TdT-mediated dUTP-biotin nick end labeling and Nissl stainings were performed in 10-MUm thickness coronal sections. Furthermore, two rabbits (without induction of ventricular fibrillation, cardiopulmonary resuscitation, and defibrillation) served as normal control group. RESULTS: Mean survival times after ROSC were 48.57 hours +/- 24.70 hours, 18.0 hours +/- 15.13 hours, and 3.88 hours +/- 2.39 hours for groups ACCA 3 minutes, ACCA-5 minutes, and ACCA-8 minutes, respectively. Survival was significantly different between ACCA-3 minutes and other two groups (p = 0.002 and p = 0.01). Neuronal necrosis and apoptosis were found in the hippocampus CA1, CA2, and CA3 areas of group ACCA-3 minutes. In contrast, neuronal necrosis and TdT-mediated dUTP-biotin nick end labeling positive cells were fewer in control animals. CONCLUSIONS: The rabbits in group ACCA-3 minutes had significant neuronal damage with apoptosis in hippocampus CA1, CA2, and CA3 areas at 72 hours after ROSC and survived longer than those in other groups. The model we describe may be a simple, economic, and reliable model for experimental investigation on cardiopulmonary cerebral resuscitation. PMID- 20571451 TI - Distal splenic artery hemodynamic changes during transient proximal splenic artery occlusion in blunt splenic injury patients: a mechanism of delayed splenic hemorrhage. AB - BACKGROUND: Delayed splenic hemorrhage after proximal splenic artery embolotherapy (SAE) in patients with blunt splenic injury is a well-known outcome. The hemorrhage is thought to be due to rupture of a splenic parenchymal pseudoaneurysm. This study attempts to explain at least part of the mechanism involved in the delayed hemorrhage event. METHODS: Hemodynamically stable patients with blunt splenic injury, without active extravasation, who underwent splenic artery angiography, also had the distal splenic artery pressure determined with transient balloon occlusion of the proximal splenic artery. RESULTS: Seven patients were referred for splenic artery angiography. The average mean aortic pressure was found to be 89.0 +/- 21.9 mm Hg. The average mean distal splenic arterial pressure with temporary proximal occlusion was 47.1 +/- 25.8 mm Hg (range = 25-98 mm Hg). The average mean pressure drop was 41.9 +/- 19.0 mm Hg or 48.0 +/- 19.3%. The average systolic pressure drop was 75.4 +/- 24.0 mm Hg (range = 40-113 mm Hg). However, one of our seven patients only had a 14.8% mean arterial pressure drop and maintained a 102 mm Hg systolic pressure in the distal splenic artery. CONCLUSIONS: The arterial pressure in the distal splenic artery after SAE is highly variable and may depend on the robustness of pre-SAE collaterals. PMID- 20571452 TI - Plasma superoxide dismutase activity and mortality in septic patients [corrected]. AB - BACKGROUND: The aim of this study was to determine whether plasma superoxide dismutase (SOD) activity, in comparison with other oxidative parameters, is associated with mortality in humans with septic. METHODS: We conducted a prospective observational study including 96 patients with septic. Blood samples were collected immediately after study inclusion and 24 hours after. We then determined plasma levels of thiobarbituric acid reactive species, protein carbonyls, SOD, and catalase activities. RESULTS: Plasma carbonyls and SOD activity, but not plasma thiobarbituric acid reactive species and catalase activity, were significantly higher in non-survivors. SOD activity significantly correlated with Acute Physiology and Chronic Health Evaluation II and Multiple Organ Dysfunction Score. In addition, SOD activity presented similar area under the receiver operator characteristic curve when compared with Acute Physiology and Chronic Health Evaluation II to predict mortality. A diminution of 25% or more on SOD activity between D1 and D2 was associated with a better outcome. CONCLUSION: Our data provide some new information on the use of plasma SOD activity as a biomarker in human sepsis. PMID- 20571453 TI - Single photon emission computed tomography demonstrated efficacy of 17beta estradiol therapy in male rats after trauma-hemorrhage and extended hypotension. AB - BACKGROUND: This study evaluated the effect of 17beta-estradiol (E2) administration on cardiovascular parameters in male rats after trauma-hemorrhage and for an extended period (3 hours) of severe hypotension, based on blood-pool single photon emission computed tomography imaging. METHODS: After a 5-cm midline laparotomy, male Sprague-Dawley rats were injected intravenously with Tc-bovine serum albumin; the animals were then bled for >45 minutes to reach maximum bleedout (MBO; removal of 60% of the circulating blood volume). E2 (1 mg/kg body weight, 0.4 mL/kg) or vehicle (cyclodextrin [CD], 0.4 mL/kg) was injected intravenously at MBO; no additional fluid was administered for 3 hours. Imaging was performed continually for a maximum of 3 hour post-MBO. The percentages of injected dose in heart, brain, liver, and kidney were quantified from the imaging (n = 8/group) at 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, and 180 minutes post-MBO. Mixed model analysis of variance was used to analyze the difference between the two groups over six imaging time points (30 180 minutes post-MBO). RESULTS: The percentages of injected dose of Tc-bovine serum albumin in heart, kidney, and liver after E2 administration were significantly higher than those after CD administration (p = 0.036, 0.025, and 0.028 for heart, kidney, and liver, respectively), whereas those in brain were not different between E2 and CD administration (p = 0.343). CONCLUSIONS: The significantly larger blood volume maintained in heart, kidney, and liver of rats after E2 therapy compared with control supports the notion that E2 produces salutary effects on the cardiovascular system after trauma-hemorrhage and even extended periods of severe hypotension. PMID- 20571454 TI - Homicide, suicide, and unintentional firearm fatality: comparing the United States with other high-income countries, 2003. AB - BACKGROUND: Violent death is a major public health problem in the United States and throughout the world. METHODS: A cross-sectional analysis of the World Health Organization Mortality Database analyzes homicides and suicides (both disaggregated as firearm related and non-firearm related) and unintentional and undetermined firearm deaths from 23 populous high-income Organization for Economic Co-Operation and Development countries that provided data to the World Health Organization for 2003. RESULTS: The US homicide rates were 6.9 times higher than rates in the other high-income countries, driven by firearm homicide rates that were 19.5 times higher. For 15-year olds to 24-year olds, firearm homicide rates in the United States were 42.7 times higher than in the other countries. For US males, firearm homicide rates were 22.0 times higher, and for US females, firearm homicide rates were 11.4 times higher. The US firearm suicide rates were 5.8 times higher than in the other countries, though overall suicide rates were 30% lower. The US unintentional firearm deaths were 5.2 times higher than in the other countries. Among these 23 countries, 80% of all firearm deaths occurred in the United States, 86% of women killed by firearms were US women, and 87% of all children aged 0 to 14 killed by firearms were US children. CONCLUSIONS: The United States has far higher rates of firearm deaths-firearm homicides, firearm suicides, and unintentional firearm deaths compared with other high-income countries. The US overall suicide rate is not out of line with these countries, but the United States is an outlier in terms of our overall homicide rate. PMID- 20571455 TI - Tourniquet use during plating of acute extra-articular tibial fractures: effects on final results of the operation. AB - BACKGROUND: Tourniquet use in orthopedics is practiced for the sake of the surgeon's comfort with a bloodless field, though it is associated with potential risks. This study was performed to assess the effects of using or avoiding a tourniquet when plating acute extra-articular tibial fractures. PATIENTS AND METHODS: One hundred thirty-eight patients with acute extra-articular tibial fractures were randomized into two groups: "tourniquet" and "without tourniquet". Postoperative pain, amount of hemovacuum drainage, and duration (time to complete bone union and nonunion, and development of infection) were assessed. RESULTS: At the end of the study, all 138 patients had been followed up for at least 1 year. The difference between the two groups was statistically significant with regard to duration of surgery, amount of hemovacuum drainage, and postoperative pain. The patients in without tourniquet group perceived less pain (p = 0.007), and their hemovacuum drainage was lesser than that of the tourniquet group (p = 0.03), though the average duration of the operation was longer (p = 0.001). CONCLUSION: Avoidance of tourniquet use does not decrease the time to union or nonunion or the infection rate after plating of tibial fractures, but it is associated with a decrease in the patient's pain perception in the postoperative period. PMID- 20571456 TI - The effect of acute traumatic brain injury on the performance of shock index. AB - BACKGROUND: Shock index (SI) is recognized to be a more reliable early indicator of hemorrhage than traditional vital signs. Acute traumatic brain injury (TBI) can be associated with autonomic uncoupling and may therefore alter the reliability of SI in patients with combined TBI and peripheral hemorrhage. The aim of this study was to evaluate the performance of SI when acute TBI of mild and moderate severity were associated with progressive simple hemorrhage. METHODS: This study was undertaken in a laboratory setting. Brian injury was induced using the lateral fluid percussion model in anesthetized rats. The fluid percussion device delivered an applied cortical pressure of 1.2 atm and 1.8 atm, producing mild and moderate TBI, respectively. Control animals underwent identical procedures but with no applied cortical pressure. Hemorrhage was induced 10 minutes after brain injury, at a rate of 2% of blood volume per minute until 40% blood volume was withdrawn. RESULTS: The SI response to increasing volume of hemorrhage was unaltered when control and mild TBI groups were compared (test of interaction p = 0.39). There was a 50% mortality rate observed 20 to 60 minutes after hemorrhage in the moderate TBI group. The SI response to hemorrhage in the moderate TBI group compared with the control group became significantly different at 40% blood volume loss (test of interaction p = 0.048). Comparison of the SI response with hemorrhage between survivors and nonsurvivors of moderate TBI revealed a significant difference (p = 0.007). SI was markedly attenuated in the presence of increasing hemorrhage in the nonsurvivor subgroup of moderate TBI. CONCLUSIONS: SI significantly underestimated underlying hemorrhage in the presence of acute TBI of moderate severity where attenuation of the biphasic heart rate and blood pressure response was also most pronounced. PMID- 20571457 TI - Time delays in the beta/gamma cycle operate on the level of individual neurons. AB - Recent studies suggested that small time delays among synchronized responses can convey information about visual stimuli. We compared these delays across different types of synchronized signals: single-unit action potentials, multi unit action potentials, and local field potentials obtained with invasive recordings from cat visual cortex and magnetoencephalographic and electroencephalographic signals recorded from the scalp of human beings. In the signals that reflected more localized sources, time delays were larger and more selective for stimulus properties than in the signals that reflected more large scale sources. The results suggest that a cortical code for stimulus features that exploits time delays operates predominantly across individual neurons rather than across larger anatomical structures such as brain areas. PMID- 20571458 TI - Abnormal regional homogeneity of drug-naive obsessive-compulsive patients. AB - To explore the possible abnormal resting-state activity in patients with obsessive-compulsive disorder (OCD), the regional homogeneity (ReHo) of 22 pairs of patients and well-matched healthy controls was calculated. Compared with controls, the patients showed higher ReHo in the left anterior cingulate cortex, but lower ReHo in the left inferior temporal gyrus. These findings supported the abnormal resting-state brain activity in drug-naive OCD patients. No significant correlations between ReHo value and four clinical characteristics were found, suggesting that abnormal ReHo might be trait-related in OCD. PMID- 20571459 TI - Involvement of DNA methylation in memory processing in the honey bee. AB - DNA methylation, an important and evolutionarily conserved epigenetic mechanism, is implicated in learning and memory processes in vertebrates, but its role in behaviour in invertebrates is unknown. We examined the role of DNA methylation in memory in the honey bee using an appetitive Pavlovian olfactory discrimination task, and by assessing the expression of DNA methyltransferase3, a key driver of epigenetic reprogramming. Here we report that DNA methyltransferase inhibition reduces acquisition retention and alters the extinction depending on treatment time, and DNA methyltransferase3 is upregulated after training. Our findings add to the understanding of epigenetic mechanisms in learning and memory, extending known roles of DNA methylation to appetitive and extinction memory, and for the first time implicate DNA methylation in memory in invertebrates. PMID- 20571460 TI - Impact of routine fluconazole prophylaxis for premature infants with birth weights of less than 1250 grams in a developing country. AB - Systemic fungal infections are associated with substantial case-morbidity and fatality rates in premature infants. Considerable evidence indicates that prophylaxis with fluconazole given to premature infants reduces the risk of invasive fungal infection. There is scant information from developing countries. A comparative study of 2 years, one with fluconazole prophylaxis and the other without was conducted in all premature babies weighing less than 1250 g at birth. Fluconazole was administered in 3 mg/kg doses, given every 48 hours, starting on day 3 of life, for a period of 6 weeks. Documented systemic Candida infection was the primary outcome. A total of 271 and 252 patients, respectively, were evaluated during the year before (control group) and after (treatment group) routine fluconazole prophylaxis. The control group developed 21 Candida infections (7.7%) while the treatment group had only 3 Candida infections (1.1%). This difference was statistically significant (P = 0.007; odds ratio, 0.13; 95% confidence interval, 0.03-0.47). The number needed to treat to prevent one case was 7. Although case-fatality rates for documented Candida infection were similar in both periods (76% vs. 67%), fewer deaths attributed to the fungal infection were noted in the prophylaxis year (6% vs. 1%, P = 0.003). Routine fluconazole prophylaxis given to premature infants of less than 1250 g at birth is associated with a significant impact on frequency of documented systemic Candida infections. PMID- 20571461 TI - Pharmacokinetics and tolerability of single-dose intravenous ertapenem in infants, children, and adolescents. AB - BACKGROUND: Ertapenem is a carbapenem antibiotic with broad spectrum activity and a pharmacokinetic profile that favors once-daily administration in adults. OBJECTIVES: This investigation was designed to evaluate the dose-exposure profile of ertapenem in children from infancy through adolescence. METHODS: Eighty-four children (3 months-16 years) requiring antibiotic therapy were enrolled in this multicenter trial. Children received a single intravenous dose of ertapenem at 15, 20, or 40 mg/kg followed by repeated blood sampling for 24 hours. Free and total plasma ertapenem concentrations were quantitated by high-performance liquid chromatography, and the pharmacokinetics were determined using a model independent approach. RESULTS: Ertapenem exposure increased proportionally with increasing dose; however, achievable concentrations were influenced by age. Children older than 12 years attained higher dose-normalized concentrations at the end of the infusion (concentration at the end of the infusion [Ceoi]: 8.7 +/- 1.9 mg/L per mg/kg dose) and total body exposure (area under the curve area under the plasma concentration-time curve [AUC]0-infinity: 34.7 +/- 14.7 mg hr/L per mg/kg dose) as compared with children 2 to 12 years (Ceoi: 6.9 +/- 2.4 mg/L per mg/kg dose, AUC0-infinity: 18.4 +/- 8.0 mg hr/L per mg/kg dose) and children younger than 2 years (Ceoi: 6.1 +/- 2.2 mg/L per mg/kg dose, AUC0-infinity: 17.0 +/- 5.4 mg hr/L per mg/kg dose). These findings were accounted for by age dependent changes in ertapenem clearance and distribution volume. In 3 children adverse events (nausea, n = 2; injection site reaction, n = 1) were considered related to study drug administration. CONCLUSIONS: Children younger than 12 years require dosing more frequently than once daily to achieve optimal efficacy when treating organisms with a minimum inhibitory concentration near the susceptibility breakpoint. PMID- 20571462 TI - Prospective determination of serum ceftazidime concentrations in intensive care units. AB - INTRODUCTION: The purpose of this study was to assess the value of a serum assay for ceftazidime (CAZ) in patients in the intensive care unit (ICU) of the Saint Etienne University Teaching Hospital and in other ICUs in the region to optimize therapy. MATERIAL AND METHODS: Between November 1, 2005, and February 29, 2008, for patients hospitalized in ICUs not on dialysis and undergoing continuous CAZ infusion, serum assay of the antibiotic was performed 36 to 48 hours after the start of treatment using a single serum sample. The target serum CAZ concentration was 40 +/- 10 mg/L with a concentration/minimum inhibitory concentration ratio of 5 or greater x minimum inhibitory concentration of CAZ when a strain was isolated. RESULTS: Serum CAZ concentration was determined in 92 patients (28 females, 64 males) receiving CAZ by continuous infusion. The mean age was 66 years (range, 19-89 years) and the mean weight was 73 kg (range, 33 122 kg). The CAZ dose was between 1 g and 6 g/24 hours. The mean serum CAZ concentration was 46.9 mg/L (range, 7.4-162.3 mg/L). Serum CAZ concentrations were as follows: 30 to 50 mg/L in 35.9% of patients, less than 30 mg/L in 36.9%, and greater than 50 mg/L in 27.2%. Infection was documented in 51 patients, with 42 strains of Pseudomonas aeruginosa being detected. The serum concentration/minimum inhibitory concentration ratio was 5 or greater for 84.3%. Antibiotic dosage was adjusted based on the CAZ assay results. CONCLUSION: Our study suggests that CAZ measurement is needed in ICUs to achieve adequate CAZ concentrations to avoid treatment toxicity and to achieve efficacy as rapidly as possible, particularly in strains having limited susceptibility to antibiotics. PMID- 20571463 TI - Therapeutic drug monitoring of methotrexate in cerebrospinal fluid after systemic high-dose infusion in children: can the burden of intrathecal methotrexate be reduced? AB - The use of intrathecal (IT) methotrexate (MTX) in combination with systemic high dose (HD) MTX is an established procedure for central nervous system prophylaxis in patients with acute lymphoblastic leukemia, but the evidence for the necessity of this combination is not convincing. The MTX concentration in the cerebrospinal fluid (CSF) was evaluated in 138 samples from children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. CSF samples were obtained by lumbar puncture 12-24 hours after starting the HD MTX infusion (5 g/m2 over 24 hours) and immediately before the IT administration of MTX. Serum MTX concentrations at the end of infusion were assessed by routine therapeutic drug monitoring. Cytotoxic MTX concentrations of 1 microM or greater were detected in 81.2% of CSF samples. CSF MTX concentrations were significantly lower in samples from patients younger than 7 years. The correlation between MTX concentrations in the serum and the CSF was moderate (r = 0.451) and became stronger with increasing age. The median CSF MTX concentrations per cycle were comparable (1.40, 1.25, 1.39, 1.38 microM for cycles 1-4, respectively). The predictive value and the accuracy of the CSF MTX concentration measured during the first cycle of HD MTX in respect to concentrations in the following cycles were high (94.4% and 85.7%, respectively) suggesting that the CSF MTX concentration during the first HD MTX infusion is a useful predictor for sufficient CSF MTX concentrations in the following HD MTX cycles. Our results confirm previously published data on MTX accumulation in the CSF after 5 g/m2 MTX over 24 hours in an independent cohort monitored in a real life setting. Based on the common opinion that 1 microM represents the minimal antileukemic MTX concentration, current data warrant reevaluation of the necessity of routine IT MTX following HD MTX. Our findings offer a perspective on reducing the burden of IT MTX in children on consolidation therapy by CSF MTX drug monitoring. PMID- 20571464 TI - The pharmacogenetics of calcineurin inhibitor-related nephrotoxicity. AB - Chronic calcineurin inhibitor (CNI)-induced nephrotoxicity is associated with prolonged use of cyclosporine and tacrolimus and has been observed after all types of transplantation, as well as during treatment of autoimmune disease. Extensive alterations in the renal architecture including glomerular sclerosis, tubular atrophy and interstitial fibrosis may lead to end-stage renal failure. Increasing evidence shows that pharmacogenetic factors explain part of the between-patient differences in susceptibility to developing CNI-induced nephrotoxicity. In this paper this evidence is reviewed, with special emphasis on the role of genetic factors influencing metabolism and transportation of CNIs in both acceptor and donor. PMID- 20571465 TI - AMP-activated protein kinase as a target for preconditioning in transplantation medicine. AB - Graft quality before transplantation is a major factor influencing chronic rejection. Organ preservation and ischemia/reperfusion play an important role in the induction of organ injury. Although both suppression of metabolism by hypothermic preservation and preconditioning before ischemia limit injury, understanding the biochemical signaling pathways will allow us to optimize graft preservation further. Adenosine monophosphate-activated protein kinase (AMPK) is an important enzyme sensing cellular energy balance and regulating downstream signaling pathways, signaling toward an energy-conserving state. In this review, we summarize available literature regarding the protective signaling pathways activated by (hypothermic) ischemia and preconditioning and how they can be activated pharmacologically. Optimizing the graft quality before transplantation improves long-term graft survival. The major factor influencing organ quality is organ preservation, cold storage, currently, being a common practice. Loss of cellular homeostasis, inflammation, and endothelial dysfunction are the major factors inducing injury after cold storage. Adenosine triphosphate depletion and anaerobic metabolism during the cold ischemic period lead to mitochondrial dysfunction, disturbed osmoregulation, and cell death inducing inflammation. Ischemic preconditioning consists of brief periods of ischemia preceding preservation and protects organs against injury because of subsequent ischemia/reperfusion, in which endothelial nitric oxide synthase, nuclear factor kB, and adenosine play a major role. After conversion of adenosine to AMP, AMPK can be activated, a central kinase involved in sensing cellular [AMP]:[adenosine triphosphate] levels and signaling toward an energy-conserving state. Pharmacologic activation of AMPK demonstrated its ability to activate endothelial nitric oxide synthase and inhibit nuclear factor-kB, thereby limiting endothelial dysfunction and inflammation. Further, studies in knock-out mice lacking ENTDP1 and NT5E (enzymes catalyzing formation and degradation of AMP, respectively) demonstrated a clear protective role for AMP in ischemia/reperfusion. AMPK activation before or during organ preservation might be a promising pharmacologic approach to limit organ injury and maintain graft quality before transplantation. PMID- 20571467 TI - Is it appropriate to implant kidneys from elderly donors in young recipients? AB - BACKGROUND: Kidneys from elderly donors tend to be implanted in recipients who are also elderly. We present the results obtained after 10 years of evolution on transplanting elderly kidneys into young recipients. METHODS: Ninety-one consecutive transplants are studied, carried out in our center with kidneys from cadaver donors older than 60 years implanted in recipients younger than 60 years. The control group is made up of 91 transplants, matched with those from the study group, whose donor and recipient were younger than 60 years. RESULTS: There were no differences between groups with regard to recipient age, sex, cause of death and renal function of the donor, hepatitis C and cytomegalovirus serologies, cold ischemia time, tubular necrosis, immediate diuresis, need for dialysis, human leukocyte antigen incompatibilities, hypersensitized patients, acute rejection, waiting time on dialysis, and days of admission. Survival in both groups at 1, 5, and 10 years was 97.6%, 87.2%, and 76.6% vs. 98.8%, 87.5%, and 69.5% for the patient (P=0.642), 92.9%, 81.3%, and 64.2% vs. 93.9%, 76.4%, and 69.5% for the graft (P=0.980), and 94.4%, 92.6%, and 77.4% vs. 94.3%, 86.7%, and 84.4% for the graft with death censured (P=0.747), respectively. Creatininaemias at 1, 5, and 10 years were 172, 175, and 210 vs. 139, 134, and 155 (P<0.05). CONCLUSIONS: We conclude that patient and graft survival on transplanting kidneys from elderly donors to young recipients is superimposable on that obtained with young donors. However, renal function is better in the group of young donors. PMID- 20571466 TI - HLA-A, -B, and -DR zero-mismatched kidneys shipped to the University of Wisconsin, Madison, 1993-2006: superior graft survival despite longer preservation time. AB - BACKGROUND: To determine the impact at a single center of the United Network for Organ Sharing-mandated sharing program for human leukocyte antigen (HLA)-A/-B/-DR 0-mismatched (0MM) kidneys, we analyzed the results of 264 kidney transplants from 0MM distant donors between 1993 and 2006, with a follow-up through January 31, 2007. We compared these results with that of concurrent kidneys transplanted from HLA more than 0MM local donors and with shipped more than 0MM kidneys from "payback" donors. RESULTS: Despite a significantly longer preservation time, we found an 11% increase in 8-year graft survival (63% vs. 52%; P<0.003) of 0MM shipped versus locally procured, >0MM donor kidneys. Graft survival of 0MM shipped kidneys at 8 years was significantly better in nonsensitized (<20% panel reactive antibodies; 68% vs. 55%; P<0.0005) but not in sensitized (>or=20% panel reactive antibodies) recipients, who showed an early (2 years) but short-lived benefit. The benefit of receiving a HLA-A, -B, and -DR 0MM shipped kidney remained strong and statistically significant (0.71 relative risk of graft loss vs. local; P<0.02) when adjusted for 22 potentially confounding variables in a Cox proportional hazards analysis. CONCLUSIONS: The recent change in United Network for Organ Sharing policy restricting mandated sharing of 0MM kidneys to sensitized and pediatric recipients will give greater flexibility to the local organ procurement organization in allocating organs. However, the survival benefit to nonsensitized patients is real and long lasting and will be lost. PMID- 20571468 TI - Intermittent antibody-based combination therapy removes alloantibodies and achieves indefinite heart transplant survival in presensitized recipients. AB - BACKGROUND: It is well established that primed/memory T cells play a critical role in heart transplant rejection. This contributes to the challenges faced in the transplant clinic because current treatments that are efficient in controlling naive T cell alloresponses have limited efficacy on primed T cell responders. METHODS: Fully MHC-mismatched heart transplantation was performed from BALB/c to C57BL/6 mice presensitized with BALB/c splenocytes 14 days pretransplantation. A combination therapy comprising CD70-, CD154-, and CD8 specific antibodies (Abs) was administered at day 0 and 4 posttransplantation with rapamycin on days 0 to 4. RESULTS: The Ab combination therapy extended heart transplant survival in presensitized recipients from median survival time 8 days (MST) to MST 78 days. A decrease in the number of splenic interferon-gamma secreting cells measured by ELISpot assay was seen in the treated group compared with the untreated controls. However, graft-infiltrating CD8+ and CD4+ T cells persisted despite treatment and the number of intragraft CD4+ T cells increased at day 30 posttransplantation. When an additional "rescue therapy" comprising the same Abs was readministered at days 30, 60, and 90 posttransplantation, T cell infiltration was reduced and indefinite graft survival was observed. Furthermore, rescue therapy resulted in gradual decrease in titer and, by day 90 posttransplantation, the complete loss of the preexisting, donor-specific Abs. CONCLUSION: We conclude that our Ab combination therapy extends allograft survival in presensitized recipients. When combined with intermittent Ab-mediated rescue therapy, this results in indefinite allograft survival and a loss of the preexisting, donor-specific Abs from the circulation. PMID- 20571469 TI - Treatment of hepatitis C in renal transplantation candidates: a single-center experience. AB - BACKGROUND: There is no consensus on hepatitis C virus (HCV) treatment in patients with renal failure. Toxicity of pegylated interferon (PEG-IFN) and ribavirin limit options; hence the ideal approach for therapy in these patients deserves attention. We report the results of kidney transplantation (KTx) candidates infected with HCV treated with PEG-IFN monotherapy. METHODS: KTx candidates with HCV infection treated with PEG-IFN monotherapy between January 2001 and February 2009 were included. Liver biopsies were performed before therapy. Response was assessed using accepted virological time points. RESULTS: From 2636 patients listed for KTx, 60 patients were tested positive for anti-HCV. Twenty-two patients were eligible for treatment. All patients were HCV treatment naive. One patient had biopsy-confirmed cirrhosis. Mean Ishak-Knodell fibrosis stage was 1.3. Ten patients (45%) achieved sustained viral response. In genotype 1 patients, there were no relapsers among early responders, despite the limited regimen. Nine patients (40%) in the cohort have had KTx. Of these, there were four responders and five nonresponders. None of the responders have had recurrence of their HCV after their KTx. CONCLUSIONS: End-stage renal disease patients with HCV can be treated successfully with PEG-IFN monotherapy. Our sustained viral response rate was 45% (10/22) in patients treated before KTx. PMID- 20571470 TI - The suction pouch for management of simple or complex enterocutaneous fistulae. AB - Containing effluent from an enterocutaneous fistula (ECF) requires expertise, critical thinking skills, and creativity. Using a combination of products readily available to WOC nurses practicing in the United States, I have designed a suction pouch that reliably contains fistula output. A standard ostomy pouch can be converted into a suction pouch by adding a large, single-lumen catheter into the pouch, sealing it, and connecting the assembly to low continuous suction. The resulting pouch can be used by itself to drain effluent from an ECF or it can be used in combination with wound dressings, or a negative pressure wound therapy system. Application of a suction pouch extends the integrity of the appliance and diverts succus away from the wound bed or the newly applied skin graft with increased reliability. This article describes the technique used to create a suction pouch, followed by 4 brief case descriptions that demonstrate feasibility of its use for the management of ECFs. PMID- 20571472 TI - Preventing heel pressure ulcers and plantar flexion contractures in high-risk sedated patients. AB - PURPOSE: An intervention using heel pressure ulcer and plantar flexion contracture prevention protocols for high-risk patients was established to promote earlier recognition of heel skin issues and provide effective prevention of both conditions. SUBJECTS AND SETTING: Fifty-three patients who were sedated, managed in an intensive care unit for 5 days or more, and had a Braden Scale score of 16 or less were treated with heel protector devices that maintained the foot in a neutral position and floated the heel off the bed. METHODS: On admission to the intensive care unit, heel skin assessment and the Braden Scale were administered to all patients. Initial ankle range of motion was measured with a goniometer on admission and before the application of the heel protector. Goniometric measurements were documented every other day. Heel assessments and the Braden Scale for Predicting Pressure Sore Prevention and Ramsay Sedation Scale scores were recorded in every shift and recorded as part of the study every other day. Measurements continued until the patient was transferred, the heel protector boot was discontinued by the physician, or the patient's Braden Scale score rose above 16. RESULTS: Application of the heel protectors led to a 50% reduction in prevalence of abnormal heel position. No patients developed plantar flexion contractures or new heel ulcers. Patients with normal heels had significantly higher Braden Scale scores compared to those with abnormal heels (P 5 .0136). CONCLUSION: Despite their high risk, no patients using the heel protector device developed a heel pressure ulcer or plantar flexion contracture. PMID- 20571473 TI - The peritoneal osmotic conductance is low well before the diagnosis of encapsulating peritoneal sclerosis is made. AB - Encapsulating peritoneal sclerosis (EPS) is a serious condition whose frequency is increasing the longer the duration of peritoneal dialysis. To identify prognostic indicators of EPS, we studied here longitudinal changes in peritoneal membrane function of patients who later developed this complication. We identified all patients with an unequivocal diagnosis of EPS who began their peritoneal dialysis in our unit over a 20-year period and matched each of them for dialysis duration and age with four control patients who completed their dialysis. The dialysate/plasma creatinine ratio increased with time in both groups but was significantly higher in the patients with EPS only at the time their dialysis was discontinued. The ultrafiltration capacity was significantly worse for at least 2 years before stopping dialysis, diverging further at the time dialysis ceased, suggesting reduced osmotic conductance in the EPS patients. Both the glucose exposure rate for the 5 years preceding stoppage of dialysis and exposure to the osmotic agent icodextrin were significantly higher. Residual renal function was less in the EPS group, but there was no significant difference in the rates of peritonitis compared to the control group. The 24 h peritoneal protein clearance was not significantly different in EPS patients, possibly due to a greater fibrous matrix. Thus, our study shows that regular peritoneal membrane function tests can identify most patients at high risk of developing EPS before its occurrence. PMID- 20571474 TI - Moderate chronic kidney disease is associated with reduced cognitive performance in midlife women. AB - Several studies have shown that general and specific cognitive dysfunction may be present during the early stages of chronic kidney disease. These studies, however, were conducted in elderly patients with comorbid conditions and used a limited battery of cognitive tests. Here we determined whether 40- to 54-year-old women in a population-based cohort in Taiwan with moderate chronic kidney disease have reduced cognitive performance. In total, 64 women with moderate chronic kidney disease (estimated glomerular filtration rate (eGFR) stage 3) were randomly matched by age and education with 192 control individuals with eGFR stage 2 or better. All patients underwent the Rey Auditory-Verbal Learning Test, visual memory, verbal fluency, Trail Making Test, digit spans, and Hospital Anxiety and Depression Scale neuropsychological tests. Women with moderate chronic kidney disease had significantly worse performance in delayed recalls and backward digit span than controls. Mixed effects modeling showed that women with moderate chronic kidney disease had reduced cognitive performance after controlling for body mass index, menopausal status, and psychosocial distress. Thus, in a population-based sample, we found that midlife women have reduced cognitive performance associated with early-stage chronic kidney disease. If confirmed, routine cognition evaluation of patients with mild chronic kidney disease may help identify this problem earlier because mild cognitive impairment can convert to dementia. PMID- 20571475 TI - Ready for the best. PMID- 20571477 TI - Exciting times for Brazilian science. Interview by Fabio Pulizzi. PMID- 20571476 TI - Brazilian science towards a phase transition. PMID- 20571479 TI - Regenerative medicine: Noodle gels for cells. PMID- 20571481 TI - Material witness: Pasta physics. PMID- 20571480 TI - Polymer hydrogels: Chaperoning vaccines. PMID- 20571482 TI - Crystal engineering in two dimensions: Surface attraction. PMID- 20571483 TI - Evidence for abnormal forward trafficking of AMPA receptors in frontal cortex of elderly patients with schizophrenia. AB - Several lines of evidence point to alterations of alpha-amino-3-hydroxyl-5-methyl 4-isoxazole-propionate (AMPA) receptor trafficking in schizophrenia. Multiple proteins, including synapse-associated protein 97 (SAP97), glutamate receptor interacting protein 1 (GRIP1), and N-ethylmaleimide sensitive factor (NSF), facilitate the forward trafficking of AMPA receptors toward the synapse. Once localized to the synapse, AMPA receptors are trafficked in a complex endosomal system. We hypothesized that alterations in the expression of these proteins and alterations in the subcellular localization of AMPA receptors in endosomes may contribute to the pathophysiology of schizophrenia. Accordingly, we measured protein expression of SAP97, GRIP1, and NSF in the dorsolateral prefrontal cortex and found an increase in the expression of SAP97 and GRIP1 in schizophrenia. To determine the subcellular localization of AMPA receptor subunits, we developed a technique to isolate early endosomes from post-mortem tissue. We found increased GluR1 receptor subunit protein in early endosomes in subjects with schizophrenia. Together, these data suggest that there is an alteration of forward trafficking of AMPA receptors as well as changes in the subcellular localization of an AMPA receptor subunit in schizophrenia. PMID- 20571484 TI - Genetic deletion of fatty acid amide hydrolase alters emotional behavior and serotonergic transmission in the dorsal raphe, prefrontal cortex, and hippocampus. AB - Pharmacological blockade of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), produces CB(1) receptor (CB(1)R)-mediated analgesic, anxiolytic like and antidepressant-like effects in murids. Using behavioral and electrophysiological approaches, we have characterized the emotional phenotype and serotonergic (5-HT) activity of mice lacking the FAAH gene in comparison to their wild type counterparts, and their response to a challenge of the CB(1)R antagonist, rimonabant. FAAH null-mutant (FAAH(-/-)) mice exhibited reduced immobility in the forced swim and tail suspension tests, predictive of antidepressant activity, which was attenuated by rimonabant. FAAH(-/-) mice showed an increase in the duration of open arm visits in the elevated plus maze, and a decrease in thigmotaxis and an increase in exploratory rearing displayed in the open field, indicating anxiolytic-like effects that were reversed by rimonabant. Rimonabant also prolonged the initiation of feeding in the novelty suppressed feeding test. Electrophysiological recordings revealed a marked 34.68% increase in dorsal raphe 5-HT neural firing that was reversed by rimonabant in a subset of neurons exhibiting high firing rates (33.15% mean decrease). The response of the prefrontocortical pyramidal cells to the 5-HT(2A/2C) agonist (+/ )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI) revealed desensitized 5-HT(2A/2C) receptors, likely linked to the observed anxiolytic-like behaviors. The hippocampal pyramidal response to the 5-HT(1A) antagonist, WAY-100635, indicates enhanced tonus on the hippocampal 5-HT(1A) heteroreceptors, a hallmark of antidepressant-like action. Together, these results suggest that FAAH genetic deletion enhances anxiolytic-like and antidepressant-like effects, paralleled by altered 5-HT transmission and postsynaptic 5-HT(1A) and 5-HT(2A/2C) receptor function. PMID- 20571486 TI - HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. AB - We have analyzed the production of the effector cytokines interleukin (IL)-17, IL 21, and IL-22 in gluten-reactive CD4(+) T cells of celiac disease patients, either cultured from small intestinal biopsies or isolated from peripheral blood after an oral gluten challenge. Combining intracellular cytokine staining with DQ2-alpha-II gliadin peptide tetramer staining of intestinal polyclonal T-cell lines, we found that gluten-specific T cells produced interferon-gamma (IFN gamma) and IL-21, but not IL-17 or IL-22, even if other T cells of the same lines produced these cytokines. Similarly, in DQ2-alpha-II-specific T cells in peripheral blood of gluten-challenged patients, very few stained for intracellular IL-17, whereas many cells stained for IFN-gamma. We conclude that gluten-reactive T cells produce IL-21 and IFN-gamma, but not IL-17. Their production of IL-21 suggests a role for this cytokine in the pathogenesis of celiac disease. PMID- 20571487 TI - Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates. AB - Although circumcision reduces male acquisition of human immunodeficiency virus type-1 (HIV-1) by 60%, the initial mechanisms of HIV-1 transmission at the foreskin remain elusive. We have established two novel and complementary models of the human adult foreskin epithelium, namely, ex vivo foreskin explants and in vitro reconstructed immunocompetent foreskins. In these models, efficient HIV-1 transmission occurs after 1 h of polarized exposure of the inner, but not outer, foreskin to mononuclear cells highly infected with HIV-1, but not to cell-free virus. HIV-1-infected cells form viral synapses with apical foreskin keratinocytes, leading to polarized budding of HIV-1, which is rapidly internalized by Langerhans cells (LCs) in the inner foreskin. In turn, LCs migrate toward the epidermis-dermis interface to form conjugates with T cells, thereby transferring HIV-1. Seminal plasma mixed with cervicovaginal secretions inhibits HIV-1 translocation. This set of results rationalizes at the cellular level the apparent protective outcome of circumcision against HIV-1 acquisition by men. PMID- 20571488 TI - Psoriasin (S100A7) is a major Escherichia coli-cidal factor of the female genital tract. AB - The female urogenital tract requires an efficient defense against bacteria, potentially derived from the adjacent intestinal tract. We have thus sought to identify the factors that protect against Escherichia coli (E. coli) in the female genital tract. Vaginal fluid from healthy human donors consistently killed E. coli in vitro and vaginal epithelium strongly expressed and secreted psoriasin. Psoriasin was constitutively produced in an organotypic vaginal epithelium model, and exposure of these cells to supernatants of E. coli cultures led to an enhanced psoriasin expression. Secreted psoriasin in vaginal fluids accounted for approximately 2.5-3% of total protein. Fractionation of vaginal fluids by high performance liquid chromatography (HPLC) showed that psoriasin co eluted with a peak of E. coli killing activity. Our data show that normal vaginal fluid contains a powerful intrinsic antimicrobial defense against E. coli and that psoriasin contributes to the innate immune response of the female genital tract. PMID- 20571489 TI - Quality of methods for assessing and reporting serious adverse events in clinical trials of cancer drugs. AB - The validity of information regarding drug toxicity in humans depends on the quality of the methods and instruments used to assess adverse drug events (ADEs). This study evaluates the quality of instruments used to assess and report ADEs to institutional review boards (IRBs) at US cancer centers. Forms from all 49 National Cancer Institute (NCI)-designated centers were assessed for utility in abstracting event type, severity, and causality; patient demographics; safety monitoring; and consequent changes in the conduct of the relevant study. Of the 55 items considered essential for ADE reporting, one item (event description) was present on all the forms. Seventy-eight percent of the instruments prompted for global introspection of the investigator, a method known to be unreliable. Of the 34 items that our panel of experts considered essential for event description, the median number of items present was four (domain = 1-11). The use of a validated tool to describe and assess event type, severity, and causality may lead to more timely, accurate identification of safety signals in cancer treatment. PMID- 20571485 TI - Affective cognition and its disruption in mood disorders. AB - In this review, we consider affective cognition, responses to emotional stimuli occurring in the context of cognitive evaluation. In particular, we discuss emotion categorization, biasing of memory and attention, as well as social/moral emotion. We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them. We then consider neuroimaging studies of affective cognition in healthy volunteers, which have led to the development of more sophisticated neural models of these processes. Disturbances of affective cognition are a core and specific feature of mood disorders, and we discuss the evidence supporting this claim, both from behavioral and neuroimaging perspectives. Serotonin is considered to be a key neurotransmitter involved in depression, and there is a considerable body of research exploring whether serotonin may mediate disturbances of affective cognition. The final section presents an overview of this literature and considers implications for understanding the pathophysiology of mood disorder as well as developing and evaluating new treatment strategies. PMID- 20571491 TI - Anti-tissue transglutaminase antibodies from celiac patients are responsible for trophoblast damage via apoptosis in vitro. AB - OBJECTIVES: The association between maternal celiac disease (CD) and both reduced fertility and increased risk of adverse pregnancy-related events has been long documented. However, no evidences are available regarding the pathogenic mechanisms of this link. The aim of this study was to determine whether anti tissue transglutaminase (anti-tTG) antibodies are involved in the damage of trophoblastic cells in vitro. METHODS: Human primary trophoblastic cells, isolated from term placenta, were exposed to anti-tTG immunoglobulin G (IgG) antibodies, both commercially available and separated from sera of three untreated celiac women. The ability of anti-tTG antibodies to bind to trophoblastic cells, invasiveness of placental cells through a layer of extracellular matrix, and the activity of cellular matrix metalloprotease (MMP) and cellular apoptosis were evaluated, as indicators of trophoblast damage, by TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) and annexin V expression. RESULTS: Anti-tTG IgG showed a specific dose- and time-dependent binding to human trophoblast. In addition, trophoblastic cells, after being exposed to anti-tTG IgG antibodies, both commercially available and separated from sera of celiac women, showed an impaired invasiveness, a decreased activity of cellular MMP, and a greater percentage of TUNEL positivity and annexin V positivity. CONCLUSIONS: We showed that the binding of anti-tTG antibodies to trophoblast might represent a key mechanism by which the embryo implantation and pregnancy outcome are impaired in untreated celiac pregnant women. Because healthy trophoblast development is essential for placental and fetal development, these data provide a novel mechanism for CD-induced infertility, early pregnancy loss, and intrauterine growth retardation. PMID- 20571492 TI - Novel blood biomarkers of pancreatic cancer-associated diabetes mellitus identified by peripheral blood-based gene expression profiles. AB - OBJECTIVES: The prognosis of pancreatic cancer is still very poor, and the ability to detect pancreatic cancer in high-risk groups at an early stage is therefore essential for improving its long-term survival. The purpose of this study was to explore specific biomarkers that can differentiate pancreatic cancer associated diabetes from type 2 diabetes, for the early detection of pancreatic cancer. METHODS: From January 2006 to July 2008, 102 peripheral blood samples were collected from 25 patients diagnosed with pancreatic cancer and diabetes, 27 patients with pancreatic cancer without diabetes, 25 patients with diabetes mellitus >5 years, and 25 healthy controls. Thirty-two samples were used in microarray experiments to find differentially expressed genes specific for pancreatic cancer-associated diabetes. The results were further validated by quantitative real-time PCR for 101 blood samples. Protein expression of selected genes in serum and tissues was also detected. RESULTS: Using microarray analysis, we found 58 genes to be unique in patients with pancreatic cancer-associated diabetes, including 23 upregulated genes and 35 downregulated genes. Eleven upregulated genes were further validated by RT-PCR, and two of these genes-vanin 1 (VNN1) and matrix metalloproteinase 9 (MMP9)-were selected for logistic regression analysis. The combination of VNN1 and MMP9 showed the best discrimination of pancreatic cancer-associated diabetes from type 2 diabetes. The protein expression of MMP9 and VNN1 was in accordance with the gene expression. CONCLUSIONS: Our results indicate that the combination of VNN1 and MMP9 may be used as a novel blood biomarker panel for the discrimination of pancreatic cancer associated diabetes from type 2 diabetes. PMID- 20571493 TI - Effect of Helicobacter pylori infection and its eradication on reflux esophagitis and reflux symptoms. AB - OBJECTIVES: We evaluated the association between current Helicobacter pylori infection and reflux esophagitis and the effect of H. pylori eradication on reflux esophagitis in a healthy screening population. METHODS: A total of 10,102 subjects in a comprehensive screening cohort were enrolled, and 4,007 subjects had follow-up after a median of 2 years. Effects of H. pylori infection on reflux esophagitis were estimated with odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression analysis. We evaluated the change in prevalence of reflux esophagitis and reflux symptoms after H. pylori eradication vs. persistence. RESULTS: The prevalence of reflux esophagitis (as classified by the Los Angeles system) was 4.9% (490/10,102). Whereas the prevalence of reflux esophagitis was 6.4% (319/4,971) in subjects without H. pylori infection, it was 3.3% (171/5,131) in subjects with infection (P<0.001). H. pylori infection had a strong negative association with reflux esophagitis in multivariate analysis (OR 0.42; 95% CI, 0.34-0.51). Compared with the prevalence of reflux esophagitis in the persistent infection group, the prevalence of reflux esophagitis increased after successful H. pylori eradication (OR 2.34; 95% CI, 1.45-3.76; P<0.001), which was comparable to that of the H. pylori-negative group (OR 2.42; 95% CI, 1.73-3.36; P<0.001). However, reflux symptoms had no association with H. pylori infection or eradication. CONCLUSIONS: In a healthy screening population, H. pylori infection had a strong negative association with reflux esophagitis, but H. pylori eradication increased the prevalence of erosive esophagitis to the level of H. pylori-negative individuals. Long-term clinical significance of newly developed erosive esophagitis after H. pylori eradication should be evaluated prospectively. PMID- 20571494 TI - Malten, a new synthetic molecule showing in vitro antiproliferative activity against tumour cells and induction of complex DNA structural alterations. AB - BACKGROUND: Hydroxypyrones represent several classes of molecules known for their high synthetic versatility. This family of molecules shows several interesting pharmaceutical activities and is considered as a promising source of new antineoplastic compounds. METHODS: In the quest to identify new potential anticancer agents, a new maltol (3-hydroxy-2-methyl-4-pyrone)-derived molecule, named malten (N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-N,N' dimethylethylendiamine), has been synthesised and analysed at both biological and molecular levels for its antiproliferative activity in eight tumour cell lines. RESULTS: Malten exposure led to a dose-dependent reduction in cell survival in all the neoplastic models studied. Sublethal concentrations of malten induce profound cell cycle changes, particularly affecting the S and/or G2-M phases, whereas exposure to lethal doses causes the induction of programmed cell death. The molecular response to malten was also investigated in JURKAT and U937 cells. It showed the modulation of genes having key roles in cell cycle progression and apoptosis. Finally, as part of the effort to clarify the action mechanism, we showed that malten is able to impair DNA electrophoretic mobility and drastically reduce both PCR amplificability and fragmentation susceptibility of DNA. CONCLUSION: Taken together, these results show that malten may exert its antiproliferative activity through the induction of complex DNA structural modifications. This evidence, together with the high synthetic versatility of maltol-derived compounds, makes malten an interesting molecular scaffold for the future design of new potential anticancer agents. PMID- 20571495 TI - Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience. AB - BACKGROUND: Thymic carcinoma (TC) is a rare aggressive tumour. Median survival with current treatments is only 2 years. Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown benefit in various other cancers. METHODS: Laboratory analyses of snap-frozen tumour tissues were performed to detect activation and genetic mutations of receptor tyrosine kinases (RTKs) in TC samples. On the basis of molecular analyses showing activation of multiple RTKs in their tumour, four patients with metastatic TCs refractory to conventional therapies were treated with sunitinib according to standard protocols. RESULTS: RTK analysis in three of the patients showed activation of multiple RTKs, including platelet-derived growth factor-beta and vascular endothelial growth factor 3. Mutations of EGFR, c-KIT, KRAS, and BRAF genes were not found. Administration of sunitinib yielded a partial remission (lasting 2 to 18+ months) according to the RECIST criteria in three patients and stable disease with excellent metabolic response in 18F-FDG-PET in another one. The overall survival with sunitinib treatment ranges from 4 to 40+ months. Withdrawal of the drug in one patient prompted rapid tumour progression that could be controlled by re administration of sunitinib. CONCLUSIONS: Sunitinib is an active treatment for metastatic TC. A panel of molecular analyses may be warranted for optimal patient selection. PMID- 20571496 TI - Vitamin B(6) supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis. AB - BACKGROUND/OBJECTIVES: The purpose of this study was to investigate whether vitamin B(6) supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA). SUBJECTS/METHODS: This was a single-blind co-intervention study performed at the Division of Allergy, Immunology and Rheumatology of Chung Shan Medical University Hospital, Taiwan. Patients were diagnosed with RA according to the 1991 American College of Rheumatology criteria for RA. Patients were randomly allocated into two groups: control (5 mg/day folic acid only; n=15) or vitamin B(6) (5 mg/day folic acid plus 100 mg/day vitamin B(6); n=20) for 12 weeks. Plasma pyridoxal 5'-phosphate (PLP), serum folate, inflammatory parameters (that is, high-sensitivity C reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)) and immune parameters (that is, white blood cell, total lymphocyte, T-cell (CD3), B-cell (CD19), T-helper cell (CD4), T-suppressor (CD8)) were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention. RESULTS: In the group receiving vitamin B(6), plasma IL-6 and TNF-alpha levels significantly decreased at week 12. There were no significant changes with respect to immune responses in both groups except for the percentage of total lymphocytes in the vitamin B(6) group when compared with week 0 and week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP after adjusting for confounders (beta=-0.01, P=0.01). CONCLUSIONS: A large dose of vitamin B(6) supplementation (100 mg/day) suppressed pro inflammatory cytokines (that is, IL-6 and TNF-alpha) in patients with RA. PMID- 20571497 TI - Is ad libitum energy intake in overweight subjects reproducible in laboratory studies using the preload paradigm? AB - We assessed the reproducibility of ad libitum energy intake (EI) in overweight/obese subjects. A total of six men and two women, with a body mass index 27-32 kg/m(2), aged 18-45 years, not currently dieting and weight stable during the past 3 months were studied. Participants' EI before the study was standardized. A 1047 kJ (250 kcal) liquid preload containing 40% energy from whey protein (that is, 25 g of whey protein isolate) or a non-energy control preload were consumed randomly 90 min before an ad libitum lunch meal. Participants completed visual analogue scales for subjective appetite after preloads, and reported food intake during the remainder of the day. Treatments were repeated twice to assess reproducibility of ad libitum EI. Mean ad libitum EI was 3811+/ 979 kJ and 3334+/-719 kJ after control- and whey protein-containing preloads, respectively. Analysis of repeated treatments showed within-treatment mean differences (+/- s.d.; day 1 minus day 2) of -50+/-251 kJ (-12+/-60 kcal), within coefficient of variation (CV) of 4.5% and intraclass correlation of 0.97 for control preloads. These results were -142+/-544 kJ ( 34+/-130 kcal), within subject CVs of 11.2% and intraclass correlations of 0.72 for whey protein containing preloads. In conclusion, ad libitum EI in a laboratory study using the preload paradigm in overweight and obese subjects was highly reproducible. PMID- 20571498 TI - Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. AB - BACKGROUND: Although high soy consumption may be associated with lower breast cancer risk in Asian populations, findings from epidemiological studies have been inconsistent. OBJECTIVE: We investigated the effects of soy intake on breast cancer risk among Korean women according to their menopausal and hormone receptor status. METHODS: We conducted a case-control study with 358 incident breast cancer patients and 360 age-matched controls with no history of malignant neoplasm. Dietary consumption of soy products was examined using a 103-item food frequency questionnaire. RESULTS: The estimated mean intakes of total soy and isoflavones from this study population were 76.5 g per day and 15.0 mg per day, respectively. Using a multivariate logistic regression model, we found a significant inverse association between soy intake and breast cancer risk, with a dose-response relationship (odds ratios (OR) (95% confidence interval (CI)) for the highest vs the lowest intake quartile: 0.36 (0.20-0.64)). When the data were stratified by menopausal status, the protective effect was observed only among postmenopausal women (OR (95% CI) for the highest vs the lowest intake quartile: 0.08 (0.03-0.22)). The association between soy and breast cancer risk did not differ according to estrogen receptor (ER)/progesterone receptor (PR) status, but the estimated intake of soy isoflavones showed an inverse association only among postmenopausal women with ER+/PR+ tumors. CONCLUSIONS: Our findings suggest that high consumption of soy might be related to lower risk of breast cancer and that the effect of soy intake could vary depending on several factors. PMID- 20571499 TI - Coffee consumption and risk of colorectal cancer. AB - BACKGROUND/OBJECTIVES: The possible association between coffee consumption and risk of colorectal cancer has been extensively studied in the many populations. The aim of this study is to examine this relationship among Finns, who are the heaviest coffee consumers in the world. SUBJECTS/METHODS: A total of 60 041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Their coffee consumption and other study characteristics were determined at baseline, and they were prospectively followed up for onset of colon and rectal cancer, emigration, death or until 30 June 2006. RESULTS: During a mean follow-up period of 18 years, 538 cases of colorectal cancer (304 cases of colon cancer and 234 cases of rectal cancer) were diagnosed. The multivariate-adjusted hazard ratio of colorectal cancer incidence for > or =10 cups of coffee per day compared with non-drinkers was 0.98 (95% CI, 0.47-2.03) for men (P for trend=0.86), 1.24 (95% CI, 0.49-3.14) for women (p for trend=0.83) and 1.03 (95% CI, 0.58-1.83) for men and women combined (P for trend=0.61). CONCLUSIONS: In this study, we found no association between coffee consumption and the risk of colorectal, colon and rectal cancer. PMID- 20571500 TI - The glycaemic potency of breakfast and cognitive function in school children. AB - OBJECTIVES: The aim of this study was to assess how the glycaemic potency (blood glucose (BG)-raising potential) of breakfast is associated with cognitive function (CF) in school children, taking into account important confounders, including iron status, underlying physiological adaptations and socio-economic status. METHODS: Sixty children aged 11-14 years were selected on the basis of having breakfast habitually. Their breakfast and any snacks eaten on the morning of the study were recorded. They were categorized into four groups according to the glycaemic index (GI) and glycaemic load (GL) of the breakfast: low-GI, high GL; high-GI, high-GL; low-GI, low-GL and high-GI, low-GL above or below the median for GI=61 and GL=27. BG levels were measured in finger-prick blood samples immediately before and immediately after the CF tests. RESULTS: A low-GI, high-GL breakfast was associated with better performance on a speed of information processing (P<0.01) and a serial sevens (P<0.001) task 90 min later; a high-GI breakfast with better performance on an immediate word recall task (P<0.01); and a high-GL breakfast with better performance on a Matrices task (P<0.01). CONCLUSIONS: GI, GL or both were associated with performance on the majority of the CF tests (4 of 7) used. This study describes the macronutrient composition of breakfast that could have a positive influence on the cognition of school children, proposes the use of both GI and GL to estimate exposure, and discusses future directions in this area of research. PMID- 20571501 TI - Dietary patterns of men in ALSPAC: associations with socio-demographic and lifestyle characteristics, nutrient intake and comparison with women's dietary patterns. AB - OBJECTIVE: The aim of this study is to obtain distinct dietary patterns using principal components analysis (PCA) in men taking part in the Avon Longitudinal Study of Parents and Children and to determine the associations with (a) the patterns derived in the study women (the men's partners), (b) socio-demographic and lifestyle factors and (c) estimated nutrient intakes. DESIGN AND METHODS: A total of 4681 men taking part in a population-based cohort study recorded their current frequency of food consumption through questionnaire. Dietary patterns were identified using PCA, and scores were calculated for each pattern. A wide variety of social and demographic characteristics and lifestyle factors were also collected through self-completion questionnaire. RESULTS: Four dietary patterns were established: 'health conscious', 'traditional', 'processed/confectionery' and 'semi-vegetarian'. There were relatively strong correlations and levels of agreement between the 'health conscious' and 'vegetarian' style patterns in men and women (P<0.001). Strong associations were evident between several socio demographic variables and the dietary patterns, similar to those earlier reported in women. Finally, nutrient intakes were plausibly associated with dietary pattern scores. CONCLUSIONS: Distinct dietary patterns in men have been identified using PCA that are similar, but not identical to those obtained in their partners at the same time point. Researchers should always consider stratifying by gender when examining dietary patterns. This study will form the basis for further work investigating the associations between parental and child dietary patterns. PMID- 20571502 TI - Genome-wide gene expression profiling of the Angelman syndrome mice with Ube3a mutation. AB - Angelman syndrome (AS) is a human neurological disorder caused by lack of maternal UBE3A expression in the brain. UBE3A is known to function as both an ubiquitin-protein ligase (E3) and a coactivator for steroid receptors. Many ubiquitin targets, as well as interacting partners, of UBE3A have been identified. However, the pathogenesis of AS, and how deficiency of maternal UBE3A can upset cellular homeostasis, remains vague. In this study, we performed a genome-wide microarray analysis on the maternal Ube3a-deficient (Ube3a(m-/p+)) AS mouse to search for genes affected in the absence of Ube3a. We observed 64 differentially expressed transcripts (7 upregulated and 57 downregulated) showing more than 1.5-fold differences in expression (P<0.05). Pathway analysis shows that these genes are implicated in three major networks associated with cell signaling, nervous system development and cell death. Using quantitative reverse transcription PCR, we validated the differential expression of genes (Fgf7, Glra1, Mc1r, Nr4a2, Slc5a7 and Epha6) that show functional relevance to AS phenotype. We also show that the protein level of melanocortin 1 receptor (Mc1r) and nuclear receptor subfamily 4, group A, member 2 (Nr4a2) in the AS mice cerebellum is decreased relative to that of the wild-type mice. Consistent with this finding, expression of small-interfering RNA that targets Ube3a in P19 cells caused downregulation of Mc1r and Nr4a2, whereas overexpression of Ube3a results in the upregulation of Mc1r and Nr4a2. These observation help in providing insights into the genesis of neurodevelopmental phenotype of AS and highlight specific area for future research. PMID- 20571503 TI - A fourth locus for autosomal dominant hypercholesterolemia maps at 16q22.1. AB - Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated increase in plasmatic low-density lipoprotein (LDL) cholesterol levels associated with high risk of premature cardiovascular disease. Mutations in LDLR, APOB, and PCSK9 genes have been shown to cause ADH. We now report further genetic heterogeneity of ADH through the study of a large French family in which the involvement of these three genes was excluded. A genome-wide scan mapped the disease-causing gene, named HCHOLA4, at 16q22.1 in a 7.89-Mb interval containing 154 genes with a maximum LOD score of 3.9. To reduce the linked region, we genotyped 18 smaller non-LDLR/non-APOB/non-PCSK9-ADH families at the HCHOLA4 locus. Six families did not exclude linkage to the locus, but none allowed reduction of the disease interval. The 154 regional genes were sorted according to the function of the encoded protein and tissue expression profiles, and 57 genes were analyzed through sequencing of their coding region and close flanking intronic parts. No disease-causing mutation was identified in these families, particularly in the LCAT gene. Finally, our results also show the existence of other ADH genes as nine families were neither linked to LDLR, APOB, and PCSK9 genes nor to the new HCHOLA4 locus. PMID- 20571504 TI - Chadic languages and Y haplogroups. PMID- 20571505 TI - A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese. AB - Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5) gene have been associated with hypertriglyceridaemia. We investigated which SNPs in the APOA5 gene were associated with triglyceride levels in two independent Chinese populations. In all, 1375 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study were genotyped for five tagging SNPs chosen from HapMap. Replication was sought in 1996 subjects from the Guangzhou Biobank Cohort Study. Among the five SNPs, rs662799 (-1131T>C) was strongly related to log-transformed triglyceride levels among Hong Kong subjects (beta=0.192, P=2.6 * 10(-13)). Plasma triglyceride level was 36.1% higher in CC compared to TT genotype. This association was confirmed in Guangzhou subjects (beta=0.159, P=1.3 * 10(-12)), and was significantly irrespective of sex, age group, obesity, metabolic syndrome, hypertension, diabetes, smoking and alcohol drinking. The odds ratios and 95% confidence interval for plasma triglycerides >=1.7 mmol/l associated with TC and CC genotypes were, respectively, 1.81 (1.37-2.39) and 2.22 (1.44-3.43) in Hong Kong and 1.27 (1.05-1.54) and 1.97 (1.42-2.73) in Guangzhou. Haplotype analysis suggested the association was due to rs662799 only. The corroborative findings in two independent populations indicate that the APOA5-1131T>C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population. PMID- 20571506 TI - Genes predict village of origin in rural Europe. AB - The genetic structure of human populations is important in population genetics, forensics and medicine. Using genome-wide scans and individuals with all four grandparents born in the same settlement, we here demonstrate remarkable geographical structure across 8-30 km in three different parts of rural Europe. After excluding close kin and inbreeding, village of origin could still be predicted correctly on the basis of genetic data for 89-100% of individuals. PMID- 20571508 TI - Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency. AB - Human FOXP2 deficiency has been identified as a cause of hereditary developmental verbal dyspraxia. Another member of the same gene family, FOXP1, has expression patterns that overlap with FOXP2 in some areas of the brain, and FOXP1 and FOXP2 have the ability to form heterodimers. These findings suggest the possibility that FOXP1 may also contribute to proper speech development. However, no such role of FOXP1 has been established to date. Recently, a child was reported who presented with a 3p13-14.1 deletion of four genes, including FOXP1, and a constellation of deficits that included speech delay. In this study, we report the case of a patient with a single deletion of FOXP1. This patient presented with speech and motor developmental delays, a Chiari I malformation, and epileptiform discharges. The nature of the speech deficit is different from the primary oromotor verbal dyspraxia found in patients with FOXP2 deficiency. The patient's developmental deficits may support a role for FOXP1 in the development of verbal and motor skills. PMID- 20571509 TI - Carrier screening for beta-thalassaemia: a review of international practice. AB - beta-thalassaemia is one of the most common single-gene inherited conditions in the world, and thalassaemia carrier screening is the most widely performed genetic screening test, occurring in many different countries. beta-thalassaemia carrier screening programmes provide a unique opportunity to compare the delivery of carrier screening programmes carried out in different cultural, religious and social contexts. This review compares the key characteristics of beta thalassaemia carrier screening programmes implemented in countries across the world so that the differences and similarities between the programmes can be assessed. The manner in which thalassaemia carrier screening programmes are structured among different populations varies greatly in several aspects, including whether the programmes are mandatory or voluntary, the education and counselling provided and whether screening is offered pre-pregnancy or antenatally. National and international guidelines make recommendations on the most appropriate ways in which genetic carrier screening programmes should be conducted; however, these recommendations are not followed in many programmes. We discuss the implications for the ethical and acceptable implementation of population carrier screening and identify a paucity of research into the outcomes of thalassaemia screening programmes, despite the fact that thalassaemia screening is so commonly conducted. PMID- 20571510 TI - Population structure and genome-wide patterns of variation in Ireland and Britain. AB - Located off the northwestern coast of the European mainland, Britain and Ireland were among the last regions of Europe to be colonized by modern humans after the last glacial maximum. Further, the geographical location of Britain, and in particular of Ireland, is such that the impact of historical migration has been minimal. Genetic diversity studies applying the Y chromosome and mitochondrial systems have indicated reduced diversity and an increased population structure across Britain and Ireland relative to the European mainland. Such characteristics would have implications for genetic mapping studies of complex disease. We set out to further our understanding of the genetic architecture of the region from the perspective of (i) population structure, (ii) linkage disequilibrium (LD), (iii) homozygosity and (iv) haplotype diversity (HD). Analysis was conducted on 3654 individuals from Ireland, Britain (with regional sampling in Scotland), Bulgaria, Portugal, Sweden and the Utah HapMap collection. Our results indicate a subtle but clear genetic structure across Britain and Ireland, although levels of structure were reduced in comparison with average cross-European structure. We observed slightly elevated levels of LD and homozygosity in the Irish population compared with neighbouring European populations. We also report on a cline of HD across Europe with greatest levels in southern populations and lowest levels in Ireland and Scotland. These results are consistent with our understanding of the population history of Europe and promote Ireland and Scotland as relatively homogenous resources for genetic mapping of rare variants. PMID- 20571511 TI - Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA. AB - Replication-factor C (RFC) is a protein complex that loads the processivity clamp PCNA onto DNA. Elg1 is a conserved protein with homology to the largest subunit of RFC, but its function remained enigmatic. Here, we show that yeast Elg1 interacts physically and genetically with PCNA, in a manner that depends on PCNA modification, and exhibits preferential affinity for SUMOylated PCNA. This interaction is mediated by three small ubiquitin-like modifier (SUMO)-interacting motifs and a PCNA-interacting protein box close to the N-terminus of Elg1. These motifs are important for the ability of Elg1 to maintain genomic stability. SUMOylated PCNA is known to recruit the helicase Srs2, and in the absence of Elg1, Srs2 and SUMOylated PCNA accumulate on chromatin. Strains carrying mutations in both ELG1 and SRS2 exhibit a synthetic fitness defect that depends on PCNA modification. Our results underscore the importance of Elg1, Srs2 and SUMOylated PCNA in the maintenance of genomic stability. PMID- 20571512 TI - Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis. AB - Histone deacetylases (HDACs) counterbalance acetylation of lysine residues, a protein modification involved in numerous biological processes. Here, Hdac1 and Hdac2 conditional knock-out alleles were used to study the function of class I Hdac1 and Hdac2 in cell cycle progression and haematopoietic differentiation. Combined deletion of Hdac1 and Hdac2, or inactivation of their deacetylase activity in primary or oncogenic-transformed fibroblasts, results in a senescence like G(1) cell cycle arrest, accompanied by up-regulation of the cyclin-dependent kinase inhibitor p21(Cip). Notably, concomitant genetic inactivation of p53 or p21(Cip) indicates that Hdac1 and Hdac2 regulate p53-p21(Cip)-independent pathways critical for maintaining cell cycle progression. In vivo, we show that Hdac1 and Hdac2 are not essential for liver homeostasis. In contrast, total levels of Hdac1 and Hdac2 in the haematopoietic system are critical for erythrocyte-megakaryocyte differentiation. Dual inactivation of Hdac1 and Hdac2 results in apoptosis of megakaryocytes and thrombocytopenia. Together, these data indicate that Hdac1 and Hdac2 have overlapping functions in cell cycle regulation and haematopoiesis. In addition, this work provides insights into mechanism-based toxicities observed in patients treated with HDAC inhibitors. PMID- 20571513 TI - Independent fusions and recent origins of sex chromosomes in the evolution and diversification of glass knife fishes (Eigenmannia). AB - The genus Eigenmannia comprises several species groups that display a surprising variety of diploid chromosome numbers and sex-determining systems. In this study, hypotheses regarding phylogenetic relationships and karyotype evolution were investigated using a combination of molecular and cytogenetic methods. Phylogenetic relationships were analyzed for 11 cytotypes based on sequences from five mitochondrial DNA regions. Parsimony-based character mapping of sex chromosomes confirms previous suggestions of multiple origins of sex chromosomes. Molecular cytogenetic analyses involved chromosome painting using probes derived from whole sex chromosomes from two taxa that were hybridized to metaphases of their respective sister cytotypes. These analyses showed that a multiple XY system evolved recently (<7 mya) by fusion. Furthermore, one of the chromosomes that fused to form the neo-Y chromosome is fused independently to another chromosome in the sister cytotype. This may constitute an efficient post-mating barrier and might imply a direct function of sex chromosomes in the speciation processes in Eigenmannia. The other chromosomal sex-determination system investigated is shown to have differentiated by an accumulation of heterochromatin on the X chromosome. This has occurred in the past 0.6 my, and is the most recent chromosomal sex-determining system described to date. These results show that the evolution of sex-determining systems can proceed very rapidly. PMID- 20571515 TI - Promomycin, a polyether promoting antibiotic production in Streptomyces spp. AB - Widespread interspecific stimulation of antibiotic production occurs in strains of Streptomyces owing to the activity of diffusible substances, as previously determined in our investigations of the cross-feeding effect. In this study, we newly isolated a substance produced by a Streptomyces strain closely related to Streptomyces scabrisporus, based on the observation that this substance induced the production of an unknown antibiotic in another strain related to Streptomyces griseorubiginosus. This substance, named promomycin, is a polyether structurally related to lonomycin. Promomycin itself had an antibiotic activity, but it stimulated antibiotic production in multiple Streptomyces strains at sub inhibitory concentrations. Evidence implies that this stimulation effect is widespread within this group of bacteria. PMID- 20571516 TI - Antimicrobial spectrum of the antitumor agent, cisplatin. PMID- 20571517 TI - Everything you never wanted to know about circular analysis, but were afraid to ask. AB - Over the past year, a heated discussion about 'circular' or 'nonindependent' analysis in brain imaging has emerged in the literature. An analysis is circular (or nonindependent) if it is based on data that were selected for showing the effect of interest or a related effect. The authors of this paper are researchers who have contributed to the discussion and span a range of viewpoints. To clarify points of agreement and disagreement in the community, we collaboratively assembled a series of questions on circularity herein, to which we provide our individual current answers in 100 Mb and has been proposed to be a strong suppressor of recombination, as well as a potential model for studying neo-sex chromosome evolution. To quantify and evaluate these features of the ZAL2(m) polymorphism, we generated sequence from 8 ZAL2(m) and 16 ZAL2 chromosomes at 58 loci inside and 4 loci outside the inversion. Inside the inversion we found that recombination was completely suppressed between ZAL2 and ZAL2(m), resulting in uniformly high levels of genetic differentiation (F(ST)=0.94), the formation of two distinct haplotype groups representing the alternate chromosome arrangements and extensive linkage disequilibrium spanning ~104 Mb within the inversion, whereas gene flow was not suppressed outside the inversion. Finally, although ZAL2(m) homozygotes are exceedingly rare in the population, occurring at a frequency of < 1%, we detected evidence of historical recombination between ZAL2(m) chromosomes inside the inversion, refuting its potential status as a non recombining autosome. PMID- 20571518 TI - In vivo serotonin-sensitive binding of [11C]CUMI-101: a serotonin 1A receptor agonist positron emission tomography radiotracer. AB - Positron emission tomography studies of 5-hydroxytryptamine (5-HT)(1A) receptors have hitherto been limited to antagonist radiotracers. Antagonists do not distinguish high/low-affinity conformations of G protein-coupled receptors and are less likely to be sensitive to intrasynaptic serotonin levels. We developed a novel 5-HT(1A) agonist radiotracer [(11)C]CUMI-101. This study evaluates the sensitivity of [(11)C]CUMI-101 binding to increases in intrasynaptic serotonin induced by intravenous citalopram and fenfluramine. Two Papio anubis were scanned, using [(11)C]CUMI-101 intravenous bolus of 4.5 +/- 1.5 mCi. Binding potential (BP(F)=B(avail)/K(D)) was measured before (n=10) and 20 minutes after elevation of intrasynaptic serotonin by intravenous citalopram (2 mg/kg, n=3; 4 mg/kg, n=3) and fenfluramine (2.5 mg/kg, n=3) using a metabolite-corrected arterial input function. Occupancy was also estimated by the Lassen graphical approach. Both citalopram and fenfluramine effects were significant for BP(F) (P=0.031, P=0.049, respectively). The Lassen approach estimated 15.0, 30.4, and 23.7% average occupancy after citalopram 2 mg/kg, 4 mg/kg, and fenfluramine 2.5 mg/kg, respectively. [(11)C]CUMI-101 binding is sensitive to a large increase in intrasynaptic serotonin in response to robust pharmacological challenges. These modest changes in BP(F) may make it unlikely that this ligand will detect changes in intrasynaptic 5-HT under physiologic conditions; future work will focus on evaluating its utility in measuring the responsiveness of the 5-HT system to pharmacological challenges. PMID- 20571519 TI - Characterization of in vivo pharmacokinetic properties of the dopamine D1 receptor agonist DAR-0100A in nonhuman primates using PET with [11C] NNC112 and [11C] raclopride. AB - DAR-0100A, the active enantiomer of dihydrexidine, is a potent dopamine D1 agonist under investigation for treatment of cognitive impairment and negative symptoms of schizophrenia. We measured the dose-occupancy relationship for DAR 0100A at D1 receptors using positron emission tomography (PET) imaging in baboons with [(11)C] NNC112 and its binding to D2 with [(11)C] raclopride. Two baboons were scanned with [(11)C] NNC112 at baseline and after three different doses of DAR-0100A. Two baboons were scanned with [(11)C] raclopride at baseline and after one dose of DAR-0100A. Occupancy (DeltaBP(ND)) was computed in the striatum and cortex. A clear relationship was observed between plasma concentration of DAR 0100A and DeltaBP(ND). DeltaBP(ND) was larger in the striatum than in the cortex, consistent with reports showing that 25% of [(11)C] NNC112 BP(ND) in the cortex is attributed to 5-HT(2A). Plasma EC(50) estimates ranged from 150 to 550 ng/mL according to the constraints on the model. There was no detectable effect of DAR 0100A on [(11)C] raclopride BP(ND). These data suggest that at doses likely to be administered to patients, occupancy will not be detectable with [(11)C] NNC112 PET and binding of DAR-0100A to D2 will be negligible. This is the first demonstration with PET of a significant occupancy by a full D1 agonist in vivo. PMID- 20571520 TI - Statistics in experimental cerebrovascular research: comparison of more than two groups with a continuous outcome variable. AB - A common setting in experimental cerebrovascular research is the comparison of more than two experimental groups. Often, continuous measures such as infarct volume, cerebral blood flow, or vessel diameter are the primary variables of interest. This article presents the principles of the statistical analysis of comparing more than two groups using analysis of variance (ANOVA). We will also explain post hoc comparisons, which are required to show which groups significantly differ once ANOVA has rejected the null hypothesis. Although statistical packages perform ANOVA and post hoc contrast at a key stroke, in this study, we use examples from experimental stroke research to reveal the simple math behind the calculations and the basic principles. This will enable the reader to understand and correctly interpret the readout of statistical packages and to help prevent common errors in the comparison of multiple means. PMID- 20571521 TI - Impaired dynamic cerebral autoregulation at extreme high altitude even after acclimatization. AB - Cerebral blood flow (CBF) increases and dynamic cerebral autoregulation is impaired by acute hypoxia. We hypothesized that progressive hypocapnia with restoration of arterial oxygen content after altitude acclimatization would normalize CBF and dynamic cerebral autoregulation. To test this hypothesis, dynamic cerebral autoregulation was examined by spectral and transfer function analyses between arterial pressure and CBF velocity variabilities in 11 healthy members of the Danish High-Altitude Research Expedition during normoxia and acute hypoxia (10.5% O(2)) at sea level, and after acclimatization (for over 1 month at 5,260 m at Chacaltaya, Bolivia). Arterial pressure and CBF velocity in the middle cerebral artery (transcranial Doppler), were recorded on a beat-by-beat basis. Steady-state CBF velocity increased during acute hypoxia, but normalized after acclimatization with partial restoration of SaO(2) (acute, 78% +/- 2%; chronic, 89% +/- 1%) and progression of hypocapnia (end-tidal carbon dioxide: acute, 34 +/ 2 mm Hg; chronic, 21 +/- 1 mm Hg). Coherence (0.40 +/- 0.05 Units at normoxia) and transfer function gain (0.77 +/- 0.13 cm/s per mm Hg at normoxia) increased, and phase (0.86 +/- 0.15 radians at normoxia) decreased significantly in the very low-frequency range during acute hypoxia (gain, 141% +/- 24%; coherence, 136% +/- 29%; phase, -25% +/- 22%), which persisted after acclimatization (gain, 136% +/- 36%; coherence, 131% +/- 50%; phase, -42% +/- 13%), together indicating impaired dynamic cerebral autoregulation in this frequency range. The similarity between both acute and chronic conditions suggests that dynamic cerebral autoregulation is impaired by hypoxia even after successful acclimatization to an extreme high altitude. PMID- 20571522 TI - Neuroglobin protects neurons against oxidative stress in global ischemia. AB - Neuroglobin (Ngb) is a recently discovered globin that affords protection against hypoxic/ischemic-induced cell injury in brain. Hypoxic/ischemic injury is associated with accumulation of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). In previous studies, we found that Ngb has antioxidative properties, and protects PC-12 cells against hypoxia- and beta-amyloid-induced cell death. To further delineate the potential role of Ngb in protection against cerebral ischemia-reperfusion injury in vivo, we developed a transgenic mouse line that overexpresses Ngb. Hippocampal ischemia-reperfusion injury was induced by a 10-minute bilateral occlusion of the common carotid arteries, and the animal brains were assessed 3 days later. CA1 neural injury was determined by cresyl violet staining. Lipid peroxidation was assessed using a malonyldialdehyde assay kit, whereas ROS/RNS accumulation was determined by Het staining in the CA1 hippocampal region. Hippocampal Ngb mRNA and protein expressions were assessed by reverse transcriptase-PCR and western blotting, respectively. Neuroglobin was successfully overexpressed in the hippocampus of Ngb transgenic mice. After ischemia-reperfusion, CA1 ROS/RNS production and lipid peroxidation were markedly decreased in Ngb transgenic mice compared with wild-type mice. Furthermore, CA1 neuronal injury was also markedly reduced. Thus, Ngb may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties. PMID- 20571523 TI - Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI. AB - Necrostatin-1 inhibits receptor-interacting protein (RIP)-1 kinase and programmed necrosis and is neuroprotective in adult rodent models. Owing to the prominence of necrosis and continuum cell death in neonatal hypoxia-ischemia (HI), we tested whether necrostatin was neuroprotective in the developing brain. Postnatal day (P)7 mice were exposed to HI and injected intracerebroventricularly with 0.1 MUL of 80 MUmol necrostatin, Nec-1, 5-(1H-Indol-3-ylmethyl)-(2-thio-3-methyl) hydantoin, or vehicle. Necrostatin significantly decreased injury in the forebrain and thalamus at P11 and P28. There was specific neuroprotection in necrostatin-treated males. Necrostatin treatment decreased necrotic cell death and increased apoptotic cell death. Hypoxia-ischemia enforced RIP1-RIP3 complex formation and inhibited RIP3-FADD (Fas-associated protein with death domain) interaction, and these effects were blocked by necrostatin. Necrostatin also decreased HI-induced oxidative damage to proteins and attenuated markers of inflammation coincidental with decreased nuclear factor-kappaB and caspase 1 activation, and FLIP ((Fas-associated death-domain-like IL-1beta-converting enzyme)-inhibitory protein) gene and protein expression. In this model of severe neonatal brain injury, we find that cellular necrosis can be managed therapeutically by a single dose of necrostatin, administered after HI, possibly by interrupting RIP1-RIP3-driven oxidative injury and inflammation. The effects of necrostatin treatment after HI reflect the importance of necrosis in the delayed phases of neonatal brain injury and represent a new direction for therapy of neonatal HI. PMID- 20571524 TI - Intact memory in TGF-beta1 transgenic mice featuring chronic cerebrovascular deficit: recovery with pioglitazone. AB - The roles of chronic brain hypoperfusion and transforming growth factor-beta 1 (TGF-beta1) in Alzheimer's disease (AD) are unresolved. We investigated the interplay between TGF-beta1, cerebrovascular function, and cognition using transgenic TGF mice featuring astrocytic TGF-beta1 overexpression. We further assessed the impact of short, late therapy in elderly animals with the antioxidant N-acetyl-L-cysteine (NAC) or the peroxisome proliferator-activated receptor-gamma agonist pioglitazone. The latter was also administered to pups as a prophylactic 1-year treatment. Elderly TGF mice featured cerebrovascular dysfunction that was not remedied with NAC. In contrast, pioglitazone prevented or reversed this deficit, and rescued the impaired neurovascular coupling response to whisker stimulation, although it failed to normalize the vascular structure. In aged TGF mice, neuronal and cognitive indices--the stimulus-evoked neurometabolic response, cortical cholinergic innervation, and spatial memory in the Morris water maze--were intact. Our findings show that impaired brain hemodynamics and cerebrovascular function are not accompanied by memory impairment in this model. Conceivably in AD, they constitute aggravating factors against a background of aging and underlying pathology. Our data further highlight the ability of pioglitazone to protect the cerebrovasculature marked by TGF-beta1 increase, aging, fibrosis, and antioxidant resistance, thus of high relevance for AD patients. PMID- 20571525 TI - Distribution of glycylsarcosine and cefadroxil among cerebrospinal fluid, choroid plexus, and brain parenchyma after intracerebroventricular injection is markedly different between wild-type and Pept2 null mice. AB - The purpose of this study was to define the cerebrospinal fluid (CSF) clearance kinetics, choroid plexus uptake, and parenchymal penetration of PEPT2 substrates in different regions of the brain after intracerebroventricular administration. To accomplish these objectives, we performed biodistribution studies using [(14)C]glycylsarcosine (GlySar) and [(3)H]cefadroxil, along with quantitative autoradiography of [(14)C]GlySar, in wild-type and Pept2 null mice. We found that PEPT2 deletion markedly reduced the uptake of GlySar and cefadroxil in choroid plexuses at 60 mins by 94% and 82% (P<0.001), respectively, and lowered their CSF clearances by about fourfold. Autoradiography showed that GlySar concentrations in the lateral, third, and fourth ventricle choroid plexuses were higher in wild type as compared with Pept2 null mice (P<0.01). Uptake of GlySar by the ependymal subependymal layer and septal region was higher in wild-type than in null mice, but the half-distance of penetration into parenchyma was significantly less in wild-type mice. The latter is probably because of the clearance of GlySar from interstitial fluid by brain cells expressing PEPT2, which stops further penetration. These studies show that PEPT2 knockout can significantly modify the spatial distribution of GlySar and cefadroxil (and presumably other peptides/mimetics and peptide-like drugs) in brain. PMID- 20571526 TI - Comparison of different exposure settings in a case--crossover study on air pollution and daily mortality: counterintuitive results. AB - Because of practical problems associated with measurement of personal exposures to air pollutants in larger populations, almost all epidemiological studies assign exposures based on fixed-site ambient air monitoring stations. In the presence of multiple monitoring stations at different locations, the selection of them may affect the observed epidemiological concentration--response (C-R) relationships. In this paper, we quantify these impacts in an observational ecologic case--crossover study of air pollution and mortality. The associations of daily concentrations of PM(10), O(3), and NO(2) with daily all-cause non violent mortality were investigated using conditional logistic regression to estimate percent increase in the risk of dying for an increase of 10 MUg/m(3) in the previous day air pollutant concentrations (lag 1). The study area covers the six main cities in the central-western part of Emilia-Romagna region (population of 1.1 million). We used four approaches to assign exposure to air pollutants for each individual considered in the study: nearest background station; city average of all stations available; average of all stations in a macro-area covering three cities and average of all six cities in the study area (50 * 150 km(2)). Odds ratios generally increased enlarging the spatial dimension of the exposure definition and were highest for six city-average exposure definition. The effect is especially evident for PM(10), and similar for NO(2), whereas for ozone, we did not find any change in the C-R estimates. Within a geographically homogeneous region, the spatial aggregation of monitoring station data leads to higher and more robust risk estimates for PM(10) and NO(2), even if monitor-to-monitor correlations showed a light decrease with distance. We suggest that the larger aggregation improves the representativity of the exposure estimates by decreasing exposure misclassification, which is more profound when using individual stations vs regional averages. PMID- 20571527 TI - Estimating perchlorate exposure from food and tap water based on US biomonitoring and occurrence data. AB - Human biomonitoring data show that exposure to perchlorate is widespread in the United States. The predominant source of intake is food, whereas drinking water is a less frequent and far smaller contributor. We used spot urine samples for over 2700 subjects and estimated 24 h intake using new creatinine adjustment equations. Merging data from surveys of national health (NHANES) with drinking water monitoring (UCMR), we categorized survey participants according to their potential exposure through drinking water or food. By subtracting daily food doses of perchlorate from the oral reference dose (RfD), we derive an allowances for perchlorate in tap water for several populations. The calculated mean food perchlorate dose in the United States was 0.081 MUg/kg/day compared to 0.101 MUg/kg/day for those who also had a potential drinking water component. The calculated 95th percentile doses, typically falling between 0.2 and 0.4 MUg/kg/day, were well below the RfD (0.7 MUg/kg/day) in all populations analyzed. Children aged 6-11 years had the highest mean perchlorate doses in food (0.147 MUg/kg/day), with an additional water contribution of only 0.003 MUg/kg/day representing just 2% of exposure. Pregnant women had a mean food dose of 0.093 vs 0.071 MUg/kg/day for all women of reproductive age. At the 95th percentile intake for both the total population and women of child-bearing age (15-44), the perchlorate contribution from food was 86% and from drinking water 14% (respectively, 30% and 5% of the RfD). At the mean for the same groups, the food to water contribution ratio is approximately 80:20. We calculate that an average 66 kg pregnant woman consuming a 90th percentile food dose (0.198 MUg/kg/day) could also drink the 90th percentile of community water for pregnant women (0.033 l/kg/day) containing 15 MUg/l perchlorate without exceeding the 0.7 MUg/kg/day reference dose. PMID- 20571529 TI - The Autism Birth Cohort: a paradigm for gene-environment-timing research. AB - The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders. PMID- 20571530 TI - Dissecting spatio-temporal protein networks driving human heart development and related disorders. AB - Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ development, we combined detailed phenotype information from deleterious mutations in 255 genes with high confidence experimental interactome data, and coupled the results to thorough experimental validation. Hereby, we made the first systematic analysis of spatio temporal protein networks driving many stages of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks, and suggests how mutations in the same genes can lead to diverse phenotypes. We observe a striking temporal correlation between organ complexity and the number of discrete functional modules coordinating morphogenesis. Our analysis elucidates the organization and composition of spatio-temporal protein networks that drive the formation of organs, which in the future may lay the foundation of novel approaches in treatments, diagnostics, and regenerative medicine. PMID- 20571531 TI - A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli. AB - The Escherichia coli chemotaxis-signaling pathway computes time derivatives of chemoeffector concentrations. This network features modules for signal reception/amplification and robust adaptation, with sensing of chemoeffector gradients determined by the way in which these modules are coupled in vivo. We characterized these modules and their coupling by using fluorescence resonance energy transfer to measure intracellular responses to time-varying stimuli. Receptor sensitivity was characterized by step stimuli, the gradient sensitivity by exponential ramp stimuli, and the frequency response by exponential sine-wave stimuli. Analysis of these data revealed the structure of the feedback transfer function linking the amplification and adaptation modules. Feedback near steady state was found to be weak, consistent with strong fluctuations and slow recovery from small perturbations. Gradient sensitivity and frequency response both depended strongly on temperature. We found that time derivatives can be computed by the chemotaxis system for input frequencies below 0.006 Hz at 22 degrees C and below 0.018 Hz at 32 degrees C. Our results show how dynamic input-output measurements, time honored in physiology, can serve as powerful tools in deciphering cell-signaling mechanisms. PMID- 20571532 TI - Dynamic CRM occupancy reflects a temporal map of developmental progression. AB - Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression. PMID- 20571533 TI - Violations of robustness trade-offs. AB - Biological robustness is a principle that may shed light on system-level characteristics of biological systems. One intriguing aspect of the concept of biological robustness is the possible existence of intrinsic trade-offs among robustness, fragility, performance, and so on. At the same time, whether such trade-offs hold regardless of the situation or hold only under specific conditions warrants careful investigation. In this paper, we reassess this concept and argue that biological robustness may hold only when a system is sufficiently optimized and that it may not be conserved when there is room for optimization in its design. Several testable predictions and implications for cell culture experiments are presented. PMID- 20571534 TI - Analysis of protein complexes through model-based biclustering of label-free quantitative AP-MS data. AB - Affinity purification followed by mass spectrometry (AP-MS) has become a common approach for identifying protein-protein interactions (PPIs) and complexes. However, data analysis and visualization often rely on generic approaches that do not take advantage of the quantitative nature of AP-MS. We present a novel computational method, nested clustering, for biclustering of label-free quantitative AP-MS data. Our approach forms bait clusters based on the similarity of quantitative interaction profiles and identifies submatrices of prey proteins showing consistent quantitative association within bait clusters. In doing so, nested clustering effectively addresses the problem of overrepresentation of interactions involving baits proteins as compared with proteins only identified as preys. The method does not require specification of the number of bait clusters, which is an advantage against existing model-based clustering methods. We illustrate the performance of the algorithm using two published intermediate scale human PPI data sets, which are representative of the AP-MS data generated from mammalian cells. We also discuss general challenges of analyzing and interpreting clustering results in the context of AP-MS data. PMID- 20571535 TI - Pharmacotherapy: Valvulopathy in patients treated for hyperprolactinemia? PMID- 20571536 TI - Diabetes: Low HbA1c levels and mortality in type 2 diabetes mellitus. PMID- 20571537 TI - Bone: Is screening for secondary causes of osteoporosis worthwhile? PMID- 20571539 TI - Robust in vivo transduction of nervous system and neural stem cells by early gestational intra amniotic gene transfer using lentiviral vector. AB - Presently, in vivo methods to efficiently and broadly transduce all major cell types throughout both the central (CNS) and peripheral adult nervous system (PNS) are lacking. In this study, we hypothesized that during early fetal development neural cell populations, including neural stem cells (NSCs), may be accessible for gene transfer via the open neural groove. To test this hypothesis, we injected lentiviral vectors encoding a green fluorescent protein (GFP) marker gene into the murine amniotic cavity at embryonic day 8. This method (i) efficiently and stably transduced the entire nervous system for at least 80% of the lifespan of the mice, (ii) transduced all major neural cell types, and (iii) transduced adult NSCs of the subventricular zone (SVZ) and subgranular zones (SGZs). This simple approach has broad applications for the study of gene function in nervous system development and adult NSCs and may have future clinical applications for treatment of genetic disorders of the nervous system. PMID- 20571538 TI - A local autocrine axis in the testes that regulates spermatogenesis. AB - Spermiation--the release of mature spermatozoa from Sertoli cells into the seminiferous tubule lumen--occurs by the disruption of an anchoring device known as the apical ectoplasmic specialization (apical ES). At the same time, the blood testis barrier (BTB) undergoes extensive restructuring to facilitate the transit of preleptotene spermatocytes. While these two cellular events take place at opposite ends of the Sertoli cell epithelium, the events are in fact tightly coordinated, as any disruption in either process will lead to infertility. A local regulatory axis exists between the apical ES and the BTB in which biologically active laminin fragments produced at the apical ES by the action of matrix metalloproteinase 2 can regulate BTB restructuring directly or indirectly via the hemidesmosome. Equally important, polarity proteins play a crucial part in coordinating cellular events within this apical ES-BTB-hemidesmosome axis. Additionally, testosterone and cytokines work in concert to facilitate BTB restructuring, which enables the transit of spermatocytes while maintaining immunological barrier function. Herein, we will discuss this important autocrine based cellular axis that parallels the hormonal-based hypothalamic-pituitary testicular axis that regulates spermatogenesis. This local regulatory axis is the emerging target for male contraception. PMID- 20571540 TI - IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques. AB - Type III/lambda interferons (IFNs) were discovered less than a decade ago and are still in the process of being characterized. Although previous studies have focused on the function of IFN-lambda 3 (also known as interleukin (IL)-28B) in a small animal model, it is unknown whether these functions would translate to a larger, more relevant model. Thus in the present study, we have used DNA vaccination as a method of studying the influence of IFN-lambda 3 on adaptive immune responses in rhesus macaques. Results of our study show for the first time that IFN-lambda 3 has significant influence on antigen-specific CD8(+) T-cell function, especially in regards to cytotoxicity. Peripheral CD8(+) T cells from animals that were administered IFN-lambda 3 showed substantially increased cytotoxic responses as gauged by CD107a and granzyme B coexpression as well as perforin release. Moreover, CD8(+) T cells isolated from the mesenteric lymph nodes (MLN) of animals receiving IFN-lambda 3 loaded significant amounts of granzyme B upon extended antigenic stimulation and induced significantly more granzyme B-mediated cell death of peptide pulsed targets. These data suggest that IFN-lambda 3 is a potent effector of the immune system with special emphasis on CD8(+) T-cell killing functions which warrants further study as a possible immunoadjuvant. PMID- 20571541 TI - A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. AB - Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects. PMID- 20571542 TI - Ex vivo expansion of retrovirally transduced primate CD34+ cells results in overrepresentation of clones with MDS1/EVI1 insertion sites in the myeloid lineage after transplantation. AB - Activation of proto-oncogenes by retroviral insertion is an important issue delaying clinical development of gene therapy. We have reported the nonrandom persistence of hematopoietic clones with vector insertions within the MDS1/EVI1 locus following transplantation of rhesus macaques. We now ask whether prolonged culture of transduced CD34(+) cells before transplantation selects for clones with insertions in the MDS1/EVI11 or other proto-oncogene loci. CD34(+) cells were transduced with standard retroviral vectors for 4 days and then continued in culture for an additional 6 days before transplantation. A 15% of insertions identified in granulocytes 6 months post-transplant were in MDS1/EVI11, significantly increased compared to the frequency in animals transplanted with cells immediately following transduction. MDS1/EVI1 clones became more dominant over time post-transplantation in one animal that was followed long term, accompanied by an increased overall copy number of vector-containing granulocytes, with one MDS1/EVI1 clone eventually accounting for 100% of transduced granulocytes and marrow colony-forming unit (CFU). This vector insertion increased the expression of Evi1 mRNA. There was no overrepresentation of MDS1/EVI1 insertions contributing to lymphoid lineages. Strategies involving prolonged ex vivo expansion of transduced cells may increase the risk of genotoxicity. PMID- 20571543 TI - Silencing of reporter gene expression in skin using siRNAs and expression of plasmid DNA delivered by a soluble protrusion array device (PAD). AB - Despite rapid progress in the development of potent and selective small interfering RNA (siRNA) agents for skin disorders, translation to the clinic has been hampered by the lack of effective, patient-friendly delivery technologies. The stratum corneum poses a formidable barrier to efficient delivery of large and/or charged macromolecules including siRNAs. Intradermal siRNA injection results in effective knockdown of targeted gene expression but is painful and the effects are localized to the injection site. The use of microneedle arrays represents a less painful delivery method and may have utility for the delivery of nucleic acids, including siRNAs. For this purpose, we developed a loadable, dissolvable protrusion array device (PAD) that allows skin barrier penetration. The PAD tips dissolve upon insertion, forming a gel-like plug that releases functional cargo. PAD-mediated delivery of siRNA (modified for enhanced stability and cellular uptake) resulted in effective silencing of reporter gene expression in a transgenic reporter mouse model. PAD delivery of luciferase reporter plasmids resulted in expression in cells of the ear, back, and footpad skin as assayed by intravital bioluminescence imaging. These results support the use of PADs for delivery of functional nucleic acids to cells in the skin with an efficiency that may support clinical translation. PMID- 20571544 TI - Neonatal gene therapy of glycogen storage disease type Ia using a feline immunodeficiency virus-based vector. AB - Glycogen storage disease type Ia (GSD-Ia), also known as von Gierke disease, is caused by a deficiency of glucose-6-phosphatase-alpha (G6Pase), a key enzyme in glucose homeostasis. From birth, affected individuals cannot maintain normal blood glucose levels and suffer from a variety of metabolic disorders, leading to life-threatening complications. Gene therapy has been proposed as a possible option for treatment of this illness. Vectors have been constructed from feline immunodeficiency virus (FIV), a nonprimate lentivirus, because the wild-type virus does not cause disease in humans. Previously, we have shown that these vectors are capable of integrating stably into hepatocyte cell lines and adult murine livers and lead to long-term transgene expression. In the current work, we have assessed the ability to attenuate disease symptoms in a murine model of GSD Ia. Single administration of FIV vectors containing the human G6Pase gene to G6Pase-alpha(-/-) mice did not change the biochemical and pathological phenotype. However, a double neonatal administration protocol led to normalized blood glucose levels, significantly extended survival, improved body weight, and decreased accumulation of liver glycogen associated with the disease. This approach shows a promising paradigm for treating GSD-Ia patients early in life thereby avoiding long-term consequences. PMID- 20571545 TI - Efficient KRT14 targeting and functional characterization of transplanted human keratinocytes for the treatment of epidermolysis bullosa simplex. AB - Inherited skin blistering conditions collectively named epidermolysis bullosa (EB) cause significant morbidity and mortality due to the compromise of the skin's barrier function, the pain of blisters, inflammation, and in some cases scaring and cancer. The simplex form of EB is usually caused by dominantly inherited mutations in KRT5 or KRT14. These mutations result in the production of proteins with dominant-negative activity that disrupt polymerization of intermediate filaments in the basal keratinocyte layer and result in a weak epidermal-dermal junction. The genome of adeno-associated virus (AAV) vectors can recombine with chromosomal sequence so that mutations can be corrected, or production of proteins with dominant-negative activity can be disrupted. We demonstrate a clinically feasible strategy for efficient targeting of the KRT14 gene in normal and EB-affected human keratinocytes. Using a gene-targeting vector with promoter trap design, targeted alteration of one allele of KRT14 occurred in 100% of transduced cells and transduction frequencies ranged from 0.1 to 0.6% of total cells. EBS patient keratinocytes with precise modifications of the mutant allele are preferentially recovered from targeted cell populations. Single epidermal stem cell clones produced histologically normal skin grafts after transplantation to athymic mice and could generate a sufficient number of cells to transplant the entire skin surface of an individual. PMID- 20571547 TI - Country by country. PMID- 20571546 TI - Introduction of an N-glycan sequon into HEXA enhances human beta-hexosaminidase cellular uptake in a model of Sandhoff disease. AB - Human lysosomal beta-hexosaminidase A is a heterodimer composed of alpha- and beta-subunits encoded by HEXA and HEXB, respectively. We genetically introduced an additional N-glycosylation sequon into HEXA, which caused amino acid substitutions (S51 to N and A53 to T) at homologous positions to N84 and T86 in the beta-subunit. The mutant HexA (NgHexA) obtained from a Chinese hamster ovary (CHO) cell line co-expressing the mutated HEXA and wild-type HEXB complementary DNAs was demonstrated to contain an additional mannose-6-phosphate (M6P)-type-N glycan. NgHexA was more efficiently taken up than the wild-type HexA and delivered to lysosomes, where it degraded accumulated substrates including GM2 ganglioside (GM2) when administered to cultured fibroblasts derived from a Sandhoff disease (SD) patient. On intracerebroventricular (i.c.v.) administration of NgHexA to SD model mice, NgHexA more efficiently restored the HexA activity and reduced the GM2 and GA2 (asialoGM2) accumulated in neural cells of the brain parenchyma than the wild-type HexA. These findings indicate that i.c.v. administration of the modified human HexA with an additional M6P-type N-glycan is applicable for enzyme replacement therapy (ERT) involving an M6P-receptor as a molecular target for HexA deficiencies including Tay-Sachs disease and SD. PMID- 20571548 TI - Chagas disease: pushing through the pipeline. PMID- 20571549 TI - The promise of T. cruzi genomics. PMID- 20571550 TI - Chagas disease in the Chaco. PMID- 20571551 TI - Campaigning for Chagas disease. PMID- 20571552 TI - Chagas disease. PMID- 20571553 TI - Chagas disease 101. PMID- 20571554 TI - Chagas disease: a new worldwide challenge. PMID- 20571555 TI - Who, how, what and where? PMID- 20571556 TI - Football crazy, fullerene mad. PMID- 20571557 TI - All a-Twitter about chemistry. PMID- 20571558 TI - Hydrophobia! PMID- 20571561 TI - Supramolecular chemistry: anion transport as easy as pi. PMID- 20571562 TI - Materials chemistry: illuminated oxides. PMID- 20571563 TI - Total synthesis: towards artificial terpene cyclases. PMID- 20571564 TI - Nitrogen activation: an iron step towards N(2) fixation. PMID- 20571566 TI - Organometallic reagents: deconstructing THF. PMID- 20571565 TI - Bioinspired chemistry: rewiring nanostructures. PMID- 20571567 TI - Catalysis: the mechanics of metathesis. PMID- 20571568 TI - 3D fabrication: behold the fold. PMID- 20571569 TI - Visible light photocatalysis as a greener approach to photochemical synthesis. AB - Light can be considered an ideal reagent for environmentally friendly, 'green' chemical synthesis; unlike many conventional reagents, light is non-toxic, generates no waste, and can be obtained from renewable sources. Nevertheless, the need for high-energy ultraviolet radiation in most organic photochemical processes has limited both the practicality and environmental benefits of photochemical synthesis on industrially relevant scales. This perspective describes recent approaches to the use of metal polypyridyl photocatalysts in synthetic organic transformations. Given the remarkable photophysical properties of these complexes, these new transformations, which use Ru(bpy)(3)(2+) and related photocatalysts, can be conducted using almost any source of visible light, including both store-bought fluorescent light bulbs and ambient sunlight. Transition metal photocatalysis thus represents a promising strategy towards the development of practical, scalable industrial processes with great environmental benefits. PMID- 20571570 TI - Experimental evidence for the functional relevance of anion-pi interactions. AB - Attractive in theory and confirmed to exist, anion-pi interactions have never really been seen at work. To catch them in action, we prepared a collection of monomeric, cyclic and rod-shaped naphthalenediimide transporters. Their ability to exert anion-pi interactions was demonstrated by electrospray tandem mass spectrometry in combination with theoretical calculations. To relate this structural evidence to transport activity in bilayer membranes, affinity and selectivity sequences were recorded. pi-acidification and active-site decrowding increased binding, transport and chloride > bromide > iodide selectivity, and supramolecular organization inverted acetate > nitrate to nitrate > acetate selectivity. We conclude that anion-pi interactions on monomeric surfaces are ideal for chloride recognition, whereas their supramolecular enhancement by pi,pi interactions appears perfect to target nitrate. Chloride transporters are relevant to treat channelopathies, and nitrate sensors to monitor cellular signaling and cardiovascular diseases. A big impact on organocatalysis can be expected from the stabilization of anionic transition states on chiral pi-acidic surfaces. PMID- 20571571 TI - Synthesis of a metal oxide with a room-temperature photoreversible phase transition. AB - Photoinduced phase-transition materials, such as chalcogenides, spin-crossover complexes, photochromic organic compounds and charge-transfer materials, are of interest because of their application to optical data storage. Here we report a photoreversible metal-semiconductor phase transition at room temperature with a unique phase of Ti(3)O(5), lambda-Ti(3)O(5). lambda-Ti(3)O(5) nanocrystals are made by the combination of reverse-micelle and sol-gel techniques. Thermodynamic analysis suggests that the photoinduced phase transition originates from a particular state of lambda-Ti(3)O(5) trapped at a thermodynamic local energy minimum. Light irradiation causes reversible switching between this trapped state (lambda-Ti(3)O(5)) and the other energy-minimum state (beta-Ti(3)O(5)), both of which are persistent phases. This is the first demonstration of a photorewritable phenomenon at room temperature in a metal oxide. lambda-Ti(3)O(5) satisfies the operation conditions required for a practical optical storage system (operational temperature, writing data by short wavelength light and the appropriate threshold laser power). PMID- 20571572 TI - Enantioselective iron-catalysed O-H bond insertions. AB - The ready availability, low price and environmentally benign character of iron mean that it is an ideal alternative to precious metals in catalysis. Recent growth in the number of iron-catalysed reactions reported reflects an increasing demand for sustainable chemistry. Only a limited number of chiral iron catalysts have been reported and these have, in general, proven less enantioselective than other transition-metal catalysts, thus limiting their appeal. Here, we report that iron complexes of spiro-bisoxazoline ligands are highly efficient catalysts for asymmetric O-H bond insertion reactions. These complexes catalyse insertions into the O-H bond of a wide variety of alcohols and even water, with exceptional enantioselectivities under mild reaction conditions. The selectivities surpass those obtained with other transition-metal catalysts. This study should inspire and encourage the use of iron instead of traditional precious metals in the development of greener catalysts for catalytic asymmetric synthesis. PMID- 20571573 TI - Chiral-auxiliary-mediated 1,2-cis-glycosylations for the solid-supported synthesis of a biologically important branched alpha-glucan. AB - Solid-phase oligosaccharide synthesis offers the promise of providing libraries of oligosaccharides for glycomics research. A major stumbling block to solid phase oligosaccharide synthesis has been a lack of general methods for the stereoselective installation of 1,2-cis-glycosides, and intractable mixtures of compounds are obtained if several such glycosides need to be installed. We have prepared on-resin a biologically important glucoside containing multiple 1,2-cis glycosidic linkages with complete anomeric control by using glycosyl donors having a participating (S)-(phenylthiomethyl)benzyl chiral auxiliary at C2. A branching point could be installed by using 9-fluorenylmethyloxycarbonyl (Fmoc) and allyloxycarbonyl (Alloc) as a versatile set of orthogonal protecting groups. The synthetic strategy made it possible to achieve partial on-resin deprotection of the completed oligosaccharide, thereby increasing the overall efficiency of the synthesis. The combination of classical and auxiliary-mediated neighbouring group participation for controlling anomeric selectivity is bringing the promise of routine automated solid-supported oligosaccharide synthesis closer. PMID- 20571574 TI - Triggering N(2) uptake via redox-induced expulsion of coordinated NH(3) and N(2) silylation at trigonal bipyramidal iron. AB - The biological reduction of N(2) to give NH(3) may occur by one of two predominant pathways in which nitrogenous N(x)H(y) intermediates, including hydrazine (N(2)H(4)), diazene (N(2)H(2)), nitride (N(3-)) and imide (NH(2-)), may be involved. To test the validity of hypotheses on iron's direct role in the stepwise reduction of N(2), model systems for iron are needed. Such systems can test the chemical compatibility of iron with various proposed N(x)H(y) intermediates and the reactivity patterns of such species. Here we describe a trigonal bipyramidal Si(o-C(6)H(4)PR(2))(3)Fe-L scaffold (R = Ph or i-Pr) in which the apical site is occupied by nitrogenous ligands such as N(2), N(2)H(4), NH(3) and N(2)R. The system accommodates terminally bound N(2) in the three formal oxidation states (iron(0), +1 and +2). N(2) uptake is demonstrated by the displacement of its reduction partners NH(3) and N(2)H(4), and N(2) functionalizaton is illustrated by electrophilic silylation. PMID- 20571575 TI - Monodisperse cylindrical micelles by crystallization-driven living self-assembly. AB - Non-spherical nanostructures derived from soft matter and with uniform size-that is, monodisperse materials-are of particular utility and interest, but are very rare outside the biological domain. We report the controlled formation of highly monodisperse cylindrical block copolymer micelles (length dispersity < or = 1.03; length range, approximately 200 nm to 2 microm) by the use of very small (approximately 20 nm) uniform crystallite seeds that serve as initiators for the crystallization-driven living self-assembly of added block-copolymer unimers with a crystallizable, core-forming metalloblock. This process is analogous to the use of small initiator molecules in classical living polymerization reactions. The length of the nanocylinders could be precisely controlled by variation of the unimer-to-crystallite seed ratio. Samples of the highly monodisperse nanocylinders of different lengths that are accessible using this approach have been shown to exhibit distinct liquid-crystalline alignment behaviour. PMID- 20571576 TI - Mechanistic insights into the ruthenium-catalysed diene ring-closing metathesis reaction. AB - Ruthenium-catalysed ring-closing metathesis (RCM) is a powerful technique for the preparation of medium-to-large rings in organic synthesis, but the details of the intimate mechanism are obscure. The dynamic behaviour of an RCM-relevant ruthenacyclobutane complex and its reactivity with ethene were studied using low temperature NMR spectroscopy to illuminate the mechanism of this widely used reaction. These kinetic and thermodynamic experiments allowed for mapping the energy surface of the key steps in the RCM reaction as mediated by Grubbs-type catalysts for alkene metathesis. The highest barrier along the RCM path is only 65 kJ mol(-1), which shows that this catalyst has extremely high inherent activity. Furthermore, this transition state corresponds to that connecting the intermediates in this reaction leading to ring opening of the cyclopentene product. This shows that ring closing is kinetically slightly favoured over ring opening, in addition to being driven by the loss of ethene. PMID- 20571577 TI - From silicon(II)-based dioxygen activation to adducts of elusive dioxasiliranes and sila-ureas stable at room temperature. AB - Dioxygen activation for the subsequent oxygenation of organic substrates that involves cheap and environmentally friendly chemical elements is at the cutting edge of chemical research. As silicon is a non-toxic and highly oxophilic element, the use of silylenes could be attractive for facile dioxygen activation to give dioxasiliranes with a SiO(2)-peroxo ring as versatile oxo-transfer reagents. However, the latter are elusive species, and have been generated and studied only in argon matrices at -233 degrees C. Recently, it was demonstrated that unstable silicon species can be isolated by applying the concept of donor acceptor stabilization. We now report the first synthesis and crystallographic characterization of dioxasiliranes stabilized by N-heterocyclic carbenes that feature a three-membered SiO(2)-peroxide ring, isolable at room temperature. Unexpectedly, these can undergo internal oxygen transfer in toluene solution at ambient temperature to give a unique complex of cyclic sila-urea with C=O --> Si=O interaction and the shortest Si=O double-bond distance reported to date. PMID- 20571578 TI - Structural evolution during the reduction of chemically derived graphene oxide. AB - The excellent electrical, optical and mechanical properties of graphene have driven the search to find methods for its large-scale production, but established procedures (such as mechanical exfoliation or chemical vapour deposition) are not ideal for the manufacture of processable graphene sheets. An alternative method is the reduction of graphene oxide, a material that shares the same atomically thin structural framework as graphene, but bears oxygen-containing functional groups. Here we use molecular dynamics simulations to study the atomistic structure of progressively reduced graphene oxide. The chemical changes of oxygen containing functional groups on the annealing of graphene oxide are elucidated and the simulations reveal the formation of highly stable carbonyl and ether groups that hinder its complete reduction to graphene. The calculations are supported by infrared and X-ray photoelectron spectroscopy measurements. Finally, more effective reduction treatments to improve the reduction of graphene oxide are proposed. PMID- 20571579 TI - Cleave and capture chemistry illustrated through bimetallic-induced fragmentation of tetrahydrofuran. AB - The cleavage of ethers is commonly encountered in organometallic chemistry, although rarely studied in the context of new, emerging bimetallic reagents. Recently, it was reported that a bimetallic sodium-zinc base can deprotonate cyclic tetrahydrofuran under mild conditions without opening its heterocyclic (OC(4)) ring. In marked contrast to this synergic sedation, herein we show that switching to the more reactive sodium-magnesium or sodium-manganese bases promotes cleavage of at least six bonds in tetrahydrofuran, but uniquely the ring fragments are captured in separate crystalline complexes. Oxide fragments occupy guest positions in bimetallic, inverse crown ethers and C(4) fragments ultimately appear in bimetallated butadiene molecules. These results demonstrate the special synergic reactivity that can be executed by bimetallic reagents, which include the ability to capture and control, and thereby study, reactive fragments from sensitive substrates. PMID- 20571581 TI - Recognizing rhenium. PMID- 20571580 TI - Hydroacylation of alpha,beta-unsaturated esters via aerobic C-H activation. AB - The development of methods for carbon-carbon bond formation under benign conditions is an ongoing challenge for the synthetic chemist. In recent years there has been considerable interest in using selective C-H activation as a direct route for generating reactive intermediates. In this article, we describe the use of aldehyde auto-oxidation as a simple, clean and effective method for C H activation, resulting in the generation of an acyl radical. This acyl radical can be used for carbon-carbon bond formation and herein we describe the application of this method for the hydroacylation of alpha,beta-unsaturated esters without the requirement of additional catalysts or reagents. This methodology generates unsymmetrical ketones, which have been shown to have broad use in organic synthesis. PMID- 20571582 TI - Small RNAs: Dispensable dicer. PMID- 20571585 TI - Endocytosis: Curvature proteins direct traffic. PMID- 20571588 TI - Responding to the challenges of breast cancer in egypt and other arab countries. AB - Physicians in Egypt and other Arab and developing countries still have to deal on a daily basis with large numbers of patients with advanced stages of breast cancer at presentation. Efforts at measuring the magnitude of the breast cancer issues, epidemiology, and awareness, are now moving further in the right direction. We are now starting to face the challenges of early detection of breast cancer as well as the implementation of proper modern management. Dorria S. Salem et al. publish in this issue of the Journal of Egyptian NCI an outline and initial results of a very ambitious Women Health Outreach Program (WHOP) designed to be completed in 5 phases 1. She and her co-authors state that those 5 phases include a prior training and demonstration phase that was completed in the Imaging Unit of Kasr El Aini Hospital in Cairo, as well as a one-year pilot phase completed between October 2007 and October 2008. Authors present us with results of screening of 20.098 women over the age of 45 years, between October 30, 2007 and February 9, 2009 in Cairo, Alexandria and Suez Governorates in Egypt. In addition to breast cancer, WHOP included screening for diabetes, hypertension and obesity. WHOP investigators are to be congratulated for this extraordinary ambitious project and all the efforts put into it. They were well prepared in regards to having a multi-disciplinary working team and they included in their project programs for training of clerks, data managers, radiographers, nurses, radiologists and other physicians who deal with diagnosis and management of breast cancer. They also included engineers and arranged for mobile units to reach women who could not otherwise reach them. WHOP investigators are to be commended also for performing a field plan demonstration project and testing it and for measuring citizens' response before finalizing their plans and starting the project1. They set a great example for other people working in the field. Breast cancer is the most common female malignancy in women in almost all Arab countries [2-5]. Randomized trials of mammographic screening of average-risk women above 50 years reduced breast cancer mortality by more than 36%. Analysis of the eight randomized trials, including the Canadian trials on women, ages 40 49 years old, showed a relative reduction of breast cancer deaths by 18% [6]. There is an obvious overlap as women with ages ranging from 40-49 years old reach the age of 50 and above, and enjoy the more clear benefits of mammographic screening beyond the age of 50 years. Many societies, including the American Cancer Society, recommend mammographic screening starting at age 40 years [7,8]. As it would be very difficult in this day and age to do more studies on breast cancer screening, and in view of the observations that almost 50% of cases are below the age of 50 years with a median age of 48-52 years at presentation, we recommend screening be done starting age 40, where resources are available and where setup for breast cancer care is appropriate [4,9]. Salem et al. report an initial very significant and alarming number of 10.215 women out of 20.098 women to be overweight and 2692 women to be obese [1]. Their observation that there is no significant correlation with breast cancer is only a one point in time observation and it cannot be used to confirm or refute any potential relationship between overweight, obesity and breast cancer. Future results, follow-up, and multivariate analysis will be awaited. Correlation of mammographic abnormalities with diabetes and hypertension in WHOP participants are very preliminary and will also need further multivariate analysis. WHOP investigators report that they invited women aged 45 years and up for screening. Eligibility criteria listed include only two points, women should have no personal history of breast cancer and no recent mammography [1], authors neither describe clinical history nor physical breast examination of selected and invited women. In future reports, authors will be asked about the assessement of those invited women, and what were the results and outcome if referred women were found to have abnormalities in their breasts. In another study from Cairo, Egypt, women were taught how to examine themselves, and authors reported that many were found to have clinical breast cancers for which they were effectively downstaged, and therefore treated for cancers that would have otherwise presented later as more advanced cases [10]. This issue brings me back to re-emphasize the importance of awareness, teaching women self-breast exam, and clinical breast examination once-a-year by a physician, particularly in countries with limited resources. Breast cancer awareness campaigns emphasize the benefits of early detection by promoting breaking of taboos, and teaching scientific facts that early breast cancer can be cured, and that cure can be achieved without the need of mastectomy. Advanced breast cancer is devastating to women and to their husbands and children, and therefore campaigns should be directed towards women as well as husbands who should be asked to encourage their wives to enroll in screening campaigns. Campaigns have begun to reduce the effects of taboos and people started to talk more freely about cancer, in fact, we and many centers in Arab countries have started to see more cases of early breast cancer and even a significant number of cases with microcalcifications [4]. Breast cancer screening in countries with limited resources have been recently reviewed [11,12]. As for the management of abnormal findings, Dorria S. Salem et al. [1] report performing FNAB as first line management in suspicious cases and reserving core biopsies for inconclusive cases. I fully agree with the authors' efforts to ensure accurate diagnosis and the importance of having an experienced cytopathologist. However, FNA is useful and recommended when there is a palpable tumor or a highly suspicious tumor with irregular borders and infiltrative characteristics on mammography and ultrasound. Core biopsy is indicated when FNA is inconclusive as the authors state, and also if mammography shows micro-calcifications where FNA cannot distinguish between in situ and infiltrative carcinoma. A core biopsy is important for better assessment of pathology and determination of receptors (estrogen, progesterone, and HER2 receptors) especially in patients with large tumors who require preoperative (neoadjuvant) therapy, particularly when targeted anti-HER2 therapy is indicated [13]. In the present report, WHOP investigators [1] report that 31 patients, out of 86 true positive cancers, underwent modified radical mastectomy while 21 had breast-conserving surgery. Eleven patients required only excisional biopsy and had benign tumors, 25 had surgery at private institutions and no data is available on them. Further WHOP reports will be awaited to report to us on the stages and follow-up information on all patients. Availability of experienced surgeons and radiation oncology are also important issues when referring patients for partial or total mastectomy. After screening of over 20000 women, authors report that abnormal mammographies with BiRADS 4 and 5 were found in 433 cases (reported as 2.1%). Additional work-up with ultrasound and FNA/biopsy showed 2 false negatives, 110 false positives, and confirmed 86 true positive cases (0.4% of total 20.098 women screened). In the US, the likelihood of a woman being called back for additional testing after first round of screening is an average of 11% (range 3-57%) [14]. In women for whom a biopsy is then indicated, the likelihood of finding an invasive and/or insitu cancer is 25-47% [15]. This is what we call positive predictive value (PPV) and it varies with expertise and patients own risk factors for breast cancer. What is of concern in this present WHOP article, although not unexpected, is that more than half of the recalled women did not show up or no feedback is available on them. This should generate yet another important experience on how to deal with missing information and how to assure follow-up of patients in Egypt and other Arab countries, as well as in all limited resource countries. WHOP investigators will be asked to report in the future on screening intervals and data collection. Screening started at age 45 years, and data were analyzed by 10-year age groups starting age 50, which makes comparisons somehow difficult. In view of the high incidence of women with breast cancer with young age at presentation, it would be more helpful if WHOP investigators revise the starting age for screening mammography and make it 40 years and analyze data according to 10-year age groups starting age 40 years. On the other hand, it is important to note that increasing the time interval of periodic mammography diminished the mortality reduction by allowing undetected growth of interval cancers. Increasing the screening interval of women in their forties from annual to every 2 years or to every 3 years would diminish mortality reduction rates from 36% to 18% and to 4%, respectively [16]. Once a screening strategy is adopted, women aged 40 years and up should be screened at yearly intervals because data from Egypt and other Arab countries indicate that 50% of breast cancers are seen in women below age 50 years, and because young women have more aggressive tumors [17,18] and may be missed by two-year intervals. Finally, WHOP investigators, staff, and their sponsors are to be commended for this excellent, well planned and executed project that sets a great example for devotion for science and public health. In addition to regional and national cancer registries, they provide many new innovative approaches to characterize, diagnose and treat breast cancer in Egypt and other Arab countries. (ABSTRACT TRUNCATED) PMID- 20571586 TI - The nuclear pore complex: bridging nuclear transport and gene regulation. AB - Although the nuclear pore complex (NPC) is best known for its primary function as the key regulator of molecular traffic between the cytoplasm and the nucleus, a growing body of experimental evidence suggests that this structure participates in a considerably broader range of cellular activities on both sides of the nuclear envelope. Indeed, the NPC is emerging as an important regulator of gene expression through its influence on the internal architectural organization of the nucleus and its apparently extensive involvement in coordinating the seamless delivery of genetic information to the cytoplasmic protein synthesis machinery. PMID- 20571589 TI - Women Health Outreach Program; a New Experience for all Egyptian Women. AB - The global health community faces a challenge with breast cancer being the most common cause of cancer related death among women around the globe. Since breast cancer's pathogenesis is poorly understood, primary prevention is still a distant goal. Thus secondary prevention through early detection is the only feasible approach at present. With this strong conviction, the launching of the first Egyptian national screening program "Women Health Outreach Program" (WHOP), was announced on October 30th 2007. This project is a government- funded program that offers free breast screening for all Egyptian women above the age of 45 years. In addition to free mammograms, the program gives the participants a chance to be screened for diabetes, hypertension and obesity as well. Positively detected cases are also offered the option of free management. During the period from October 30th, 2007, up to February 9th, 2009, 20, 098 women in Cairo, Alexandria and Suez governorates were screened for breast cancer, diabetes, hypertension and obesity through the program. In this article we will represent the achievements, challenges and services delivered by WHOP. KEY WORDS: Breast cancer - Breast screening - Early detection - Breast biopsy. PMID- 20571590 TI - Prognostic value of lipoprotein lipase expression among egyptian B-chronic lymphocytic leukemia patients. AB - BACKGROUND: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a highly variable clinical course. Some patients may survive for years without need for therapy while others, although they had early treatment, the outcome is unsatisfactory. The motive to find more reliable prognostic factors apart from stage, age, tumor volume and immunoglobulin heavy chain mutations is of clinical interest. MATERIAL AND METHODS: The study was carried out on 25 CLL patients attending Hematology Clinic at Ain Shams University Hospitals. Peripheral blood sample was taken from each patient for surface CD38 and cytoplasmic zeta-chain-associated protein tyrosine kinase (ZAP-70) by flow cytometry and lipoprotein lipase (LPL) expression by real time PCR. RESULTS: We demonstrated statistically significant association between high level of LPL expression and significantly high LDH level, poor cytogenetic risk, ZAP- 70 expression and response to therapy (p=0.01, 0.02, 0.04 and 0.001 respectively). CONCLUSIONS: LPL expression can serve as a new surrogate prognostic factor for CLL patients and can be used to detect patients who need early treatment. KEYWORDS: Lipoprotein lipase - ZAP-70 - Chronic lymphocytic leukemia. PMID- 20571591 TI - Primary Gastrointestinal Non-Hodgkin's Lymphoma: A Retrospective Study with Emphasis on Prognostic Factors and Treatment Outcome. AB - PURPOSE: The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, prognostic factors and treatment results in patients with primary gastrointestinal non-Hodgkin's lymphomas (PGI NHL). PATIENTS AND METHODS: We carried out analysis of 208 patients of PGI NHL during the time period from January 1997 to January 2007 at the Clinical Oncology Department, Tanta University Hospital to evaluate clinical features and treatment outcome. RESULTS: A total of 74.5% of patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.2% and 7.2% of the cases, respectively. Multiple gastrointestinal (MGI) involvement was in 6.3%. Approximately 84% of the PGI NHL were in stages IE/IIE. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue (MALT) type. Most intestinal NHL were of high grade NHL. The median follow-up time was 89.3 months. The site of origin, disease stage, complete resection of the tumor and histologic grade were the most important significant prognostic factors affecting disease-free (DFS) and overall survivals (OS). Numbers in intestinal lymphomas were too small for subanalyses. The OS and DFS after 5 years were 78.5% and 72.3% respectively in all patients with PGI NHL. CONCLUSIONS: Primary gastrointestinal non-Hodgkin's lymphomas are heterogenous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. Although this is a retrospective study, a stomachconserving approach may be favored. KEY WORDS: Gastrointestinal neoplasms - NHL - Gastrointestinal lymphoma - Prognostic factors - Survival. PMID- 20571587 TI - Adherens junctions: from molecules to morphogenesis. AB - How adhesive interactions between cells generate and maintain animal tissue structure remains one of the most challenging and long-standing questions in cell and developmental biology. Adherens junctions (AJs) and the cadherin-catenin complexes at their core are therefore the subjects of intense research. Recent work has greatly advanced our understanding of the molecular organization of AJs and how cadherin-catenin complexes engage actin, microtubules and the endocytic machinery. As a result, we have gained important insights into the molecular mechanisms of tissue morphogenesis. PMID- 20571592 TI - Reconstruction of segmental hemi-mandibular defects using soft tissue flaps in patients with severe comorbidity and advanced head and neck cancer. AB - BACKGROUND AND PURPOSE: The standard of care to reconstruct segmental oro mandibular defects following head and neck oncological resection is to use osseocutaneous free-tissue transfer. Some patients however are not suitable for this type of complex reconstruction. The purpose of this paper is to study our results of soft-tissue flap reconstruction for segmental hemi-mandibular defects. PATIENTS AND METHODS: Ten patients were included in the study, all had advanced squamous cell carcinoma of the oropharynx or oral cavity and all had hemimandibulectomies. RESULTS: In eight cases a vertical rectus abdominis myocutaneous (VRAM) free flap was used and in two cases a pectoralis major myocutaneous pedicled flap was used. Normal oral feeding was achieved in six patients with a mean time for discontinuation of tube feeding of 18 days. CONCLUSION: In selected patients with severe comorbidity and advanced oro mandibular cancer, soft tissue flaps may be used for segmental hemi-mandibular defects. KEY WORDS: Oral cavity cancer - Free tissue transfer. PMID- 20571593 TI - Immunohistochemical expression of survivin in breast carcinoma: relationship with clinicopathological parameters, proliferation and molecular classification. AB - BACKGROUND AND OBJECTIVE: Survivin is a novel member of the inhibitor of apoptosis (IAP) gene family. It is associated with more aggressive behavior and parameters of poor prognosis in most human cancers including gastric, colorectal and bladder carcinomas. However, conflicting data exist on its prognostic effect in breast cancer. This current study is designed to assess survivin expression in breast carcinoma relating results with clinicopathological parameters, proliferation (MIB-1) and molecular classification MATERIAL AND METHODS: Our retrospective study comprised of 65 archived cases of breast carcinoma. Samples from the tumor and the adjacent normal breast tissue were immunostained for survivin and MIB-1. Nuclear and cytoplasmic survivin expression was evaluated in normal breast tissue and carcinoma regarding both the intensity and the percentage of positive cells. ER, PR, HER2 were used as surrogate markers to classify the cases into four molecular subtypes. RESULTS: Survivin expression was detected in 78.5% of breast carcinomas. The adjacent normal breast tissue was immunonegative. Survivin expression showed significant association with increased tumor size (p<0.0001), high histologic grade (p=0.04), lymph node metastases (p<0.001), advanced tumor stage (p<0.0001), MIB-1 expression (p=0.02), negative estrogen receptor status (p=0.01) and negative progesterone receptor status (p<0.0001). The subcellular localization of survivin significantly related to histologic grade, stage and lymph node involvement. The percentage of TNP (triple negative phenotype) and HER2+/ER-PR- tumors expressing survivin were significantly higher compared to the Luminal subtypes (p=0.01). CONCLUSION: Survivin expression was associated with parameters of poor prognosis in breast cancer. Moreover, the cancer-specific expression of survivin, coupled with its importance in inhibiting cell death and in regulating cell division, makes it a potential target for novel cancer treatment. KEY WORDS: Breast carcinoma - Immunohistochemistry - MIB-1 - Molecular classification - Survivin. PMID- 20571594 TI - Diagnostic accuracy and pitfalls of preoperative fine needle aspiration cytology in salivary gland lesions. AB - PURPOSE: Evaluation of diagnostic accuracy of preoperative fine needle aspiration cytology (FNAC) in salivary gland lesions. PATIENTS AND METHODS: This is a retrospective study of 82 patients presented at NCI, Cairo University with salivary gland lesion who underwent preoperative FNAC diagnosis with subsequent excision and histopathologic assessment. Cytology results were classified as negative, positive, suspicious for cancer and inadequate. The definitive histopathologic report according to WHO Histological typing was the gold standard diagnosis against which FNAC was compared. RESULTS: Our study included 82 patients who underwent preoperative FNAC of major salivary glands with subsequent surgical excision. Male to female ratio was 1.4: 1. The median age was 42 years. Parotid gland was involved in (68.3%), submandibular in (28%) and submental gland in (3.7%). Forty cases (48.8%) were cytologically diagnosed as benign lesions, 26 (31.7%) were malignant and 10 (12.2%) were suspicious. Cytological findings were nondiagnostic in 6 (7.3%). The most common benign cytologic diagnosis was pleomorphic adenoma; 16 out of 40 cases (40%), while the most common malignant tumor was carcinoma; 22 out of 26 cases (84.6%). Cytologic diagnoses were compared with histopathologic ones and were true-negative in 37 (92.5%), true positive in 33 (91.6%), false-negative in 3 (8.3%) and false-positive in 3 (7.5%) cases regarding detection of malignant tumors. The cytologic diagnosis achieved a sensitivity of 91.7%; a specificity of 92.5%, PPV 91.6%, NPV 92.5% and diagnostic accuracy 92%. The rates of agreement of histopathologic type for benign and malignant tumors were 89.2% and 91%, respectively. CONCLUSION: The sensitivity, specificity and diagnostic accuracy of FNAC were 91.7%, 92.5% and 92%, respectively. Attention to subtle morphologic changes, pitfalls and limitations are important to increase diagnostic accuracy. Multidirectional aspiration is preferred to avoid selective sampling. Re-aspiration of solid portion after cyst fluid aspiration is necessary to decrease the rate of inadequacy. KEY WORDS: FNAC - Salivary gland lesions - Accuracy - Pitfalls. PMID- 20571595 TI - Reconstruction of the proximal humerus after wide resection of tumors: comparison of three reconstructive options. AB - PURPOSE: Assessment of the functional results and complications of three bone reconstructive procedures after resection of primary tumors of the proximal humerus. MATERIAL AND METHODS: Between 2000 and 2008, 32 patients having primary malignant, aggressive benign or metastatic tumors of the proximal humerous were selected for limb sparing surgery. Preoperative evaluation included CT chest, MRI. Limb sparing surgical resection was done including intraarticular or extraarticular wide resection of the tumor. Bone defect was reconstructed with fusion shoulder using free vascularized fibular graft (FFFG) in 11 patients and pedicled lateral scapular crest graft (PLSCG) in 8 patients and mobile shoulder reconstruction using proximal humerus prosthesis in 13 patients. Those patients were followed-up at regular interval to detect bone union and complications related to bone flaps or prosthesis. Functional results were assessed for every patient after one year postoperatively. RESULTS: The median age of the patients was 21 years and the follow-up period ranged from 19 months to 92 months. Postoperative resection margins were negative in all cases. The mean length of the resected humerus was 13cm. The mean operative time for prosthesis cases was 3.5 hours and that for FVFG was 6.5 hours and was 5 hours for PLSCG cases. The mean time of bone union proximally and distally for FVFG and PLSCG was 4.2 and 5.5 months accordingly. At 1 year follow-up, the functional results for the three reconstructive procedures were nearly the same with a mean functional score for FVFG cases was 73%, for PLSCG cases was 68% and was 71% for prosthesis cases. Hand and elbow functions were preserved in all types of reconstruction. The range of shoulder abduction and flexion was grossly limited with prosthesis cases while it showed marked improvement with fusion by FVFG and PLSCG. Complications for prosthesis cases were one case proximal migration and one case posterior sublaxation. Complications of bone flaps were nonunion of one end in 2 cases of PLSCG and one case of FVFG. Limb shortening was seen in 32 cases with PLSCG. CONCLUSION: Summarizing our experience in this small study, we can state that, limb sparing surgical resection of tumors of the proximal humerus is effective in local tumor control and preserving hand and elbow movements. MSTS functional score of the limb after reconstruction and shoulder fusion with FVFG or PLSCG is nearly the same as mobile shoulder reconstruction with endoprosthesis. Shoulder range of movement was grossly limited with prosthesis replacement while a wider range of movement was obtained with shoulder fusion. Pedicled lateral scapular crest graft is able to bridge defects only up to 12cm whereas the fibula can replace a longer defect. Selection between those reconstructive options should be individualized and is based on the age, the length of defect, the type of resection, intraarticular or extraarticular, preservation of deltoid and axillary nerve, the prognosis of the tumor. KEY WORDS: Proximal humerus tumors - Reconstruction - Limb salvage. PMID- 20571596 TI - Isolation and Immuno-Phenotypic Characterization of Tumor Infiltrating Lymphocytes (TILs) Obtained from Breast Malignant Tumor Tissues of Egyptian Patients. AB - BACKGROUND: Isolation and phenotypic characterization of tumor infiltrating lymphocytes (TILs) in some malignant tumors have been shown. TILs possess a good prognostic value as well as a therapeutic effect in these solid tumors. Our preliminary work shed some light on a good possibility of synthesis and secretion of specific protease enzyme system with a dimeric structure above 92 kDa for the lytic activity of TILs against breast tumor cells propagated ex vivo. PURPOSE: This work aims at first isolation, activation and immuno-phenotypic characterization of TILs derived from malignant tumor tissues of breast cancer patients. Second, to optimize the conditions for the biological therapeutic efficiency of the identified TILs subpopulations as targeted cell therapy against breast cancer. PATIENTS AND METHODS: The present work presented twelve patients with breast cancer from NCI, Cairo. Tcell isolation, activation, immunophenotyping and immunohistochemical investigations were performed. Enzymatic digestion method, mesh with pore size 355 & 45mm and flow cytometric analysis were used. RESULTS: The results revealed that, lymphocytes infiltrating the malignant tumor tissues were mainly of the Tcell type indicated by CD45RO positive markers as shown by immunohistochemical observations. The immunophenotypic analysis of the isolated TILs obtained from breast tumor tissues specimens and activated with interleukin- 2 (IL-2), showed that the ratio of CD4+/CD8+ was 0.89 which represents helper and cytotoxic sub-populations of TILs, respectively. Meanwhile, the ratio of CD4+/CD25+ was 16.03 representing the regulatory system of TILs subpopulation. In the peripheral blood of patients, the percentages of the CDs positive cells were different and the ratio of CD4+/CD8+ was 1.14+/-0.57 whereas the ratio of CD4+/CD25+ was 18.38+/-5.95. After mixing the isolated TILs and the T-lymphocytes obtained from the peripheral blood, the ratio of CD4+/CD8+ increased insignificantly to 1.45+/-0.67. Also the ratio of CD4+/CD25+ increased rough insignificantly, to 23.64+/-9.83. CONCLUSION: The isolated and identified TILs subpopulations have to be tested for their biological therapeutic efficacy first at ex-vivo level using the cr51 release assay; second at in-vivo level using experimental animal models as a sub-clinical investigation before going further to clinical study of using TILs as targeted bio-immunotherapy against human cancers. KEY WORDS: TILs - Immunohistochemistry - Immunophenotyping - Breast cancer. PMID- 20571597 TI - Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series. AB - AIM: We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. PATIENTS AND METHODS: In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. RESULTS: Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multifocal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received postcystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from postoperative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors, for this conservative approach, the overall survival (OS) was (84.4%) and the recurrence-free survival (RFS) was (41.3%), at 18 months; which are comparable to those reported in the literature for the delayed cystectomy approach. CONCLUSION: Adjuvant intravesical therapy with BCG with repeated cystoscopies, and delayed radical cystectomy until progression to the invasive disease carries a significant risk of mortality from invasive disease. This treatment policy may be acceptable for T1G3 bladder TCC, without concomitant carcinoma in situ (CIS), who don't recur after intravesical BCG, however, patients who progress to invasive disease may skip stage II disease and present with stage III or IV, with consequent poor survival. Therefore, due to the aggressive biologic behavior of T1G3 cancer, a determination of a cutoff number for recurrence(s) or better evaluation parameters are needed, to proceed with cystectomy without awaiting muscle invasion. KEY WORDS: Superficial bladder cancer - T1G3 TCC - Delayed cystectomy - BCG. PMID- 20571598 TI - Pediatric Non Metastatic Non Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTSS): Five Years Experience from NCI-Egypt. AB - PURPOSE: Evaluation of demographic, pathological, and clinical patterns in addition to treatment outcome of pediatric NRSTS patients treated at the NCI, Egypt. PROCEDURE: 21 pediatric patients of NRSTS between 2001 and 2006 were included. Clinical and pathological diagnosis and subtyping verification were done. Patients' cohort formed of 3 treatment groups. (1) Patients who underwent complete surgical resection with no adjuvant therapies. (2) Patients who received chemotherapy and complete surgical resection, and group (3) Patients with localized unrersectable tumors for whom systemic chemotherapy only was given. Demographic, clinicopathological variables, and treatment modalities were statistically evaluated and compared with the outcome. RESULTS: Tumors of unknown histiogenesis followed by MPNST and myxofibrosarcoma were the most frequent tumor subtypes. Low tumor grade was in favor of better outcome. With a median follow up of 2-years; respectively 100% and 81.1% of patients who had complete surgical resection of a localized disease with or without chemotherapy entered in CR (p=0.01). Local failure rate was 27.2% among CR patients (n=17). Two patients suffered local recurrance and one had distant disease metastasis. CONCLUSIONS: Complete surgical resection with or without chemotherapy is the mainstay of therapy for localized NRSTS. Tumor grade and surgical resection of NRSTS are 2 important predictors of prognosis. KEY WORDS: Nonrhabdomyosarcoma - Soft tissue sarcoma - Pediatric. PMID- 20571599 TI - The paraneoplastic limbic encephalitis: MRI characterization of a deceiving neurological disorder. AB - OBJECTIVE: Establishing diagnostic MRI criteria for such a pathological entity to enable the oncologist to modify the treatment plan combating the neurological deficits from a different diagnostic prospective, hence improving the quality of life of cancer patients. MATERIAL AND METHODS: Sixty patients from the National Cancer Institute (Cairo University) diagnosed with different types of cancer at time interval of one year were included in the study pool. Twenty patients were known to have lung cancer, 15 patients with breast cancer, 10 patients with lymphoma and 15 patients with leukemia. No age or sex predilection. All patients performed cranial MRI before and after intravenous contrast media injection, backed by the clinical assumption of encephalopathy and wide spectrum of neurological symptoms as seizures, dementia and behavioral disorders. Some of the patients with positive MRI studies performed serological test to detect onconeuronal antibodies. The study was carried out from January till December 2007. RESULTS: Thirty three patients' revealed definite MRI signal abnormality involving the limbic system proper and further temporal lobes affection while five patients revealed mixed pattern of regional encephalitic changes including the cerebellum, frontal lobes and brain stem. The rest of the study group exhibited no signs of encephalitis. CONCLUSIONS: Specific MRI appearance could be traced in paraneoplastic limbic encephalitis thus establishing diagnostic pattern for such entity that could help characterizing the disease with subsequent impact upon the treatment protocol resulting in regaining normal brain faculties and better life quality for such cancer patients. KEY WORDS: Paraneoplastic - Limbic encephalitis - MRI. PMID- 20571600 TI - Multidisciplinary approach to wilms' tumor: a retrospective analytical study of 53 patients. AB - AIM OF THE WORK: The aim of this work was to assess the epidemiologic aspects, clinico-pathological features and the results of multidisciplinary treatment of Wilms' tumor (WT) in pediatric patients treated at the National Cancer Institute (NCI), Cairo University, between January 2002 and December 2004. PATIENTS AND METHODS: This study included 53 patients, all under the age of 16 years, with previously untreated WT. Initial evaluation of all patients comprised laboratory investigations and radiological assessment which included chest X-ray and CT, abdomino-pelvic ultrasonography and CT. Doppler study of the renal vein and vena cava and bone scan were done when needed. Neoadjuvant chemotherapy was given to patients suffering from poor general condition, extensive tumor thrombus in the renal vein, irresectable and bilateral (stage V) nephroblastoma. Otherwise, up front nephrectomy was the standard therapeutic approach in this study. RESULTS: The age of the patients ranged from 2 to 108 months with a mean of 39.9 months (+/-22.56). Males and females were almost equal in number (50.9% and 49.1% respectively). Tumors were located in the left kidney in 52.8%, right kidney in 41.5% and bilaterally in only 5.7% of the cases. An abdominal mass was the most common clinical presentation (77.4%). Favorable histology was found in 86.3% while unfavorable histology was elicited in 13.7% of the cases. Congenital anomalies were recorded in 4 patients. Stage I and III were the most common (29.4% each), followed by stage II and IV (17.7% each), and finally by stage V (5.9%). Neoadjuvant chemotherapy was given to 27 cases while up-front nephrectomy was undertaken in 26 cases. Intra-operative spillage occurred in 12% of patients who had preoperative chemotherapy and 31% of those who had upfront nephrectomy. Postoperative abdominal radiotherapy was given to 32 patients. Twenty five patients underwent renal bed irradiation only, while in the other 7 whole abdominal irradiation was used. Additional chest bath (1200 cGy) was given to 7 patients. Complete remission (CR) was achieved in 74%, while death during neoadjuvant therapy took place in 4% of the cases. Disease progression during treatment was noticed in 8%. These patients were all treated with radio- and chemotherapy. Fatal outcome supervened in 75% of these, whereas in 25%, CR could be accomplished. Relapse after remission occurred in 14%. A 2nd CR could be achieved in 28.5% with a survival rate of 21.4%. Patients who relapsed >12 months after 1st CR had a 14 month-survival rate of 37.5% compared to 0% in those who relapsed <12 months after 1st CR. Disease-free survival (DFS) at 2 years was 82.4%, while overall survival (OAS) at 2 years was 78.9%. Therapy-related complications were mainly related to chemotherapy in 49% of patients and surgery in 5.9%. CONCLUSION: Tight communication between the surgical, the medical and the radiation oncologists, together with the pathologist, is indispensable for better management of WT patients. Regional lymph node biopsy and accurate marking of residual disease are essential components of surgical treatment and heroic surgical attempts are unnecessary. Neoadjuvant chemotherapy, which is still a fertile source of debate, could possibly help to avoid excessive post-operative radiotherapy and its potential complications. Tumor stage and age of patient were found to affect the results of treatment of Wilms' tumor; but the only statistically significant determinant of prognosis was histologic differentiation. Finally, further studies including molecular markers are needed to augment therapy for the blastemal predominance subtype or for favorable histology associated with loss of heterozygosity (LOA) at chromosomes 1p and 16q aiming at improved survival. KEY WORDS: Wilms' tumor - Nephroblastoma. PMID- 20571601 TI - Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review. AB - People with HIV infection have several risk factors for developing neuropsychiatric adverse events: preexisting conditions, HIV disease stage, and antiretroviral treatment. The most widely used system for assessing neuropsychiatric adverse events in clinical trials is the US Division of AIDS severity grading scale, from Grade 1 (mild) to Grade 4 (life-threatening). First line treatment with efavirenz has been associated with higher rates of neuropsychiatric adverse events than several other antiretrovirals. A MEDLINE search identified 17 randomized clinical trials of first-line HAART with two nucleoside analogs plus efavirenz, of which 13 reported neuropsychiatric adverse events using the Grade 1-4 system. The percentage of patients with graded neuropsychiatric adverse events, and the system used for analysis, was compared across the trials. Of the 13 trials identified, there were five different methods used to report neuropsychiatric adverse events: Grade 1-4 all, Grade 1-4 drug related, Grade 2-4 all, Grade 2-4 drug related, Grade 3-4 all, Grade 3-4 drug related, and adverse events leading to discontinuation. In addition, three trials used questionnaire-based methods instead of the Division of AIDS grading system. There were a significantly higher percentage of patients with Grade 1-4 neurological or psychiatric adverse events in the efavirenz versus comparator arms in the DMP-006, TMC278-C204, and STARTMRK trials. There were generally too few patients with each individual neuropsychiatric adverse event to allow meaningful comparisons of treatment arms. There were no significant differences in Grade 3 or 4 neuropsychiatric adverse events between the treatment arms in the ACTG 5142 or 2NN trials. In summary, there is a wide range of different systems used to report neuropsychiatric adverse events in HIV clinical trials. Use of a standardized endpoint would improve the interpretability of results across clinical trials. PMID- 20571602 TI - Tough decisions faced by people living with HIV: a literature review of psychosocial problems. AB - People living with HIV have faced a new situation since the arrival of the antiretroviral treatments. HIV has become a long-term condition, which not only affects physical health, but also causes psychological and social problems because of stigma and discrimination. These challenges present many decisions and dilemmas for people living with HIV, which involve complex emotional and psychological issues. The aim of this study was to examine the psychosocial decision needs of people living with HIV. To undertake the literature review, a search strategy was designed. Sources included databases (Web of Science, Scopus, ProQuest, and PubMed) as well as electronic journals (AIDS and Behavior, AIDS Care, and Social Science and Medicine). The following search terms were used: (HIV) AND (decision making; OR decision need; OR decision) AND (psychosocial; OR psychological; OR social). All languages were included, using articles from 1990 to 2009. The search was conducted from September 2008 to November 2009, and identified 123 articles. After analysis, 46 articles were included for detailed assessment. The results show that people living with HIV face three key decisions: (i) whether or not to disclose their diagnosis to others; (ii) decisions about adherence to treatments; and (iii) decisions about sexual activity and desires about parenthood. Problems associated with these decisions often result in isolation and mental illness such as depression and anxiety, lack of access to social support, and refusal to seek treatment. Despite the importance of HIV and its public health impact, few studies have considered the psychosocial needs of people living with HIV, but the results demonstrated the burden as a consequence of those needs and that greater support would be of benefit to face them in an effective way. Therefore, the results of this review highlight the requirement to develop interventions to support the psychosocial needs of people living with HIV, to accurately reflect the views and needs of the target users. PMID- 20571603 TI - Covering all bases in HIV research: unveiling a hidden world of viral evolution. AB - The advent of next-generation sequencing technologies has greatly impacted genomic research by providing a means for increasing the amount of sequence information in a cost effective fashion. Among the major next-generation sequencing technologies, the Roche 454 platform has been widely adopted in HIV research. We discuss a broad range of applications of the 454 pyrosequencing platform in the HIV field, with a particular emphasis on antiretroviral therapy and virus-host interaction-related research. We also highlight some of the bioinformatics challenges, as well as advantages and potential limitations of this "deep" sequencing tool, and hint at future research applications. PMID- 20571604 TI - Dual role of host cell factors in HIV-1 replication: restriction and enhancement of the viral cycle. AB - Once HIV-1 enters the target cell, the first goal in the viral cycle is to integrate into the cellular chromosomes. The irreversible integration as a provirus allows HIV-1 to persist in the infected cell in a quiescent or latent stage that leads to viral escape from immune response and current antiviral treatment. HIV-1 replication is absolutely dependent on different cellular and viral factors that initiate viral expression, acting at the long terminal repeat of the integrated provirus. Accordingly, HIV-1 induces changes in the cellular environment to make possible an efficient replication and production of viral progeny. One main instigator of HIV-1 replication is the viral regulator Tat, which is absolutely required for efficient transcription and elongation of viral transcripts. For this purpose, Tat recruits several cellular proteins to make the chromatin structure accessible for the transcription machinery, to acquire the posttranslational modifications essential for its function, and to produce efficient viral replication. However, the host cell has also several antiviral mechanisms that may act at different steps of the viral cycle to thwart HIV-1 replication. To level the match, HIV-1 encodes accessory proteins, such as Vif and Vpu, which play important roles in HIV-1 pathogenesis by counteracting cellular antiviral factors. The increasing knowledge of viral protein interactions with host cell factors will be essential for the discovery of new targets that could be used to design new therapeutic strategies. PMID- 20571605 TI - Biological, psychosocial, therapeutic and quality of life inequalities between HIV-positive men and women - a review from a gender perspective. AB - The proportion of women infected with HIV worldwide has grown in recent years. From a transmission pattern that was once predominantly homosexual men and through intravenous use of drugs, the current pattern has become, to a large extent, heterosexual. Women are more vulnerable to be infected with HIV due to anatomical and psychosocial differences. In spite of this changing gender trend in the HIV pandemic, biological, psychosocial, therapeutic, and quality of life aspects have not been examined in detail in women. Moreover, this lack of investigation has relevance in terms of vertical transmission of the infection to newborns. Herein, we review gender differences in HIV, identifying from a gender perspective the biological and social factors with a greater influence on vulnerability to infection, and, on the other hand, examining gender differences with respect to the use of services, treatment, survival, and quality of life. PMID- 20571606 TI - Niacin and laropiprant. AB - Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant. PMID- 20571608 TI - Peramivir and its use in H1N1 influenza. AB - A novel H1N1 influenza virus of swine origin has emerged, causing the first pandemic of the 21st century. Infections with 2009 pandemic influenza A (H1N1) are typically moderate. However, in rare cases, respiratory distress, neurological complications and death have been reported. To alleviate complications associated with 2009 H1N1 influenza infection, the neuraminidase (NA) inhibitors oseltamivir (oral) and zanamivir (inhaled) are recommended. Hospitalized patients with severe complications may not respond to these drugs or be able to receive oral antiviral therapy, and therefore, parenteral formulations that would allow rapid delivery at high concentrations are being pursued. Peramivir is a novel potent NA inhibitor currently in clinical trials for intravenous (i.v.) administration. In clinical trials, i.v. peramivir was shown to be safe and well tolerated, with a pharmacokinetic profile that supports once daily dosing. Based on the safety and efficacy of i.v. peramivir in clinical trials and the need for a parenteral antiviral, the U.S. Food and Drug Administration issued an Emergency Use Authorization (EUA) for the use of peramivir for the treatment of hospitalized patients with known or suspected 2009 H1N1 influenza infection. In Japan, peramivir has been licensed under the name Rapiacta. The development of peramivir leading to the issuance of the EUA and approval in Japan will be discussed. PMID- 20571607 TI - Oxycodone combinations for pain relief. AB - No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment. PMID- 20571609 TI - A review of preserved and preservative-free prostaglandin analogues for the treatment of open-angle glaucoma and ocular hypertension. AB - Glaucoma affects an increasing number of people worldwide and is the second leading cause of blindness. The aim of antiglaucoma therapy is to maintain a patient's visual function and quality of life. Prostaglandin analogues are first line topical antiglaucoma therapy. They are effective at lowering intraocular pressure (IOP) and are generally well tolerated, with fewer systemic adverse events compared with the other classes. However, the use of prostaglandin analogues can be associated with ocular adverse effects, such as stinging/burning sensation, dry eyes, iris and periocular hyperpigmentation, and eye lash growth, which can affect patient compliance. Preservatives used in antiglaucoma preparations can have dose-dependent toxic effects, which contribute to adverse effects. The development of preservative-free preparations may reduce such adverse effects and therefore improve patient compliance. Tafluprost is a prostaglandin analogue in a preservative-free formulation that was recently approved for the reduction of elevated IOP in open-angle glaucoma and ocular hypertension. PMID- 20571610 TI - Oxybutynin topical and transdermal formulations: an update. AB - Oxybutynin, an antimuscarinic agent, is well established for the treatment of overactive bladder (OAB) and is the gold standard for the treatment of severe neurogenic bladder. Although oral oxybutynin is effective in relieving the urinary symptoms of OAB, medication adherence is low at least in part because of substantial anticholinergic adverse effects. The poor anticholinergic tolerability has been attributed to high circulating levels of N desethyloxybutynin (DEO), a pharmacologically active product of presystemic metabolism of oral oxybutynin in the liver and gastrointestinal tract. Transdermal formulations of oxybutynin avoid first-pass metabolism and thereby produce lower DEO plasma concentrations. Oxybutynin chloride topical gel (OTG) (Gelnique(R), Watson Pharmaceuticals, Corona, CA, USA), a new gel-based transdermal formulation of oxybutynin, was approved by the U.S. Food and Drug Administration in January 2009. Results of a placebo-controlled U.S. phase III study demonstrated that OTG is efficacious in relieving symptoms of OAB and is associated with a low incidence of anticholinergic adverse events. Patients may find that OTG, with its excellent efficacy, convenient once-daily application and outstanding tolerability profile, is a valuable alternative to oral antimuscarinic agents for the treatment of OAB. PMID- 20571611 TI - Cardiovascular outcome of an angiotensin II receptor blocker, candesartan, in Japan. AB - Candesartan cilexetil, an angiotensin II receptor blocker (ARB), was discovered in Japan in 1982. By the end of 2009, five randomized prospective clinical trials had been conducted in Japan. Herein, we examine the similarities and differences in the results with ARB reported from abroad and Japan. Candesartan reduced blood pressure of hypertensive patients to <140/90 mmHg with an average dose of 8 mg/day. In addition, candesartan reduced the incidence of cardiovascular events in a high-risk Japanese group of patients. From the analysis of the data obtained, candesartan-based treatment for hypertensive patients with and/or without cardiovascular diseases was effective in the Japanese population, as well as in subjects in Western countries. PMID- 20571612 TI - A report from the 4th biennial conference of the international society of bipolar disorder (March 17-20, 2010 - Sao Paulo, Brazil). AB - Bipolar disorder has a significant prevalence in the overall population, and carries considerable functional impairment for sufferers as well as a very negative impact on their relatives and caregivers. These facts were widely accepted by attendees to this year's biannual conference of the International Society for Bipolar Disorder, as was the concept that, although less apparent due to the lack of overt mania, type II bipolar disorder is not a mild form of the disease, but an even worse condition with severe depressive episodes that carry a high risk for suicide. And suicide is, in fact, among the most fearful threats of bipolar disorder. Sao Paulo, and this year's ISBD meeting, offered an opportunity for discussing treatments for patients suffering from manic, depressive and mixed states associated with bipolar disorder, and this report will review and summarize findings directly related to pharmacotherapy for the disease. PMID- 20571613 TI - A report from the 68th annual meeting of the American Academy of Dermatology (March 5-9, 2010 - Miami, Florida, USA). AB - Although a study using eye-tracking technology to assess the focus of attention when evaluating the beauty of a face demonstrated a marked attentional preference for the eye area (Cula, G.O. et al., Abst P1636), the skin at large is a main factor that reveals information about a person to everyone else with whom he or she comes into contact. Be it because of disease or because of aging, improving the appearance of the skin is as important as relieving pain, itch or other troublesome symptoms caused by skin diseases. Moreover, this can be much more important in a place like South Miami Beach, where bare skin is revealed on much more than just the face ... at least under normal circumstances, when the weather is not as surprisingly chilly as it was in March 2010 during the AAD annual meeting However, if beauty is very important for many people, health is important for everybody, and important news was also discussed on treatments for common and less common cutaneous diseases, ranging from psoriasis, acne and atopic dermatitis to a broad range of blistering, papulosquamous and granulomatous diseases. These are among the most important issues reviewed in the following report, which in combination with expert insight interviews freely accessible from the Access Dermatology website and the full abstracts from the meeting, available for download from the AAD website, will hopefully improve dermatologists' approach to treating skin diseases through use of the most novel therapies. Treatment is important, but so is prevention, and in that sense an important issue discussed during the meeting, which was nicely covered in an interview with Dr. Darrell S. Riegel from the Ronald O. Perelman Department of Dermatology at the New York University School of Medicine, was that protecting the skin from sunlight and artificial tanning beds is essential for preventing malignancies such as melanoma, while not jeopardizing adequate availability of active vitamin D. A fitting message is: "It's cold, but even if it wasn't, cover your skin... even in Miami". PMID- 20571614 TI - Fluorescence resonance energy transfer between phenanthrene and PAMAM dendrimers. AB - We describe herein an adsorption-induced energy transfer between phenanthrene, a major environmental pollutant, and a fluorescently labeled dendrimer acting as a host molecule. We find experimentally that such energy transfer is the most efficient at a solvent pH of 8 and for a phenanthrene:dendrimer molar ratio of 1:2. Using molecular dynamics simulations we show that the strongest binding interactions occur between phenanthrene and the primary amines of the dendrimer. The simulations provide evidence that at low pH, phenanthrene-phenanthrene interactions are favorable and compete with phenanthrene-dendrimer binding. This study offers a new scheme for detecting dendrimer molecular assembly and a physical basis for exploiting dendrimer nanotechnologies for water purification and environmental remediation. PMID- 20571615 TI - Laser trapping and picosecond time-resolved spectroscopy of water droplets in air: cavity-enhanced spontaneous emission of Ru(bpy)(3)Cl(2). AB - Whispering gallery mode (WGM) resonances were observed in the emission spectrum of Ru(bpy)(3)(2+) (bpy = 2,2'-bipyridine) in a single laser-trapped water droplet levitated in air. The emission decay profiles of Ru(bpy)(3)(2+) in the water droplets comprised fast and slow decay components. The emission lifetime of the slow decay component was independent of the diameter of the droplet, and corresponded to the value in a bulk aqueous solution. On the other hand, the emission lifetime of the fast decay component decreased with decreasing the droplet diameter, which could be ascribed to the cavity-enhanced spontaneous emission. The decrease in the emission lifetime of the fast decay component as a function of the droplet diameter was explained on the basis of cavity quantum electrodynamic (QED) effects. It was shown that the mode characteristic of WGM resonances and the enhancement factor of the radiative rate of Ru(bpy)(3)(2+) were controlled by the size of the water droplet. PMID- 20571616 TI - Constituents of Amoora cucullata with TRAIL resistance-overcoming activity. AB - In search of bioactive natural products for overcoming TRAIL resistance from natural resources, we previously reported a number of active compounds. Bioassay guided fractionation of mangrove, Amoora cucullata, collected from Sundarbans Mangrove Forest, Bangladesh, led to the isolation of four new compounds (1-4), along with seven known compounds (5-11). Of the isolates, compounds 1, 5, 8, and 9 showed TRAIL resistance-overcoming activity, among which 8 showed the most potent activity and enhanced TRAIL-induced apoptosis in TRAIL-resistant human gastric adenocarcinoma (AGS) cells through the activation of caspase-3/7, enhancing the expression of DR4 and DR5 mRNA in AGS cells. Cell death caused by the combined treatment of 8 and TRAIL was inhibited by human recombinant DR5/Fc and DR4/Fc chimera proteins, indicating that 8 sensitizes TRAIL-resistant AGS cells to TRAIL through the induction of DR4 and DR5. PMID- 20571617 TI - Enhanced performance of a dye-sensitized solar cell with the incorporation of titanium carbide in the TiO2 matrix. AB - The effects of incorporation of various weight percentages of titanium carbide (TiC) into TiO(2) matrices on the photovoltaics of the respective dye-sensitized solar cells (DSSCs) were investigated. It is established through relevant photographs, XRD and EDX analysis that TiC was partially converted into anatase TiO(2) (a-TiO(2)) when the TiC was sintered at 450 degrees C. With the incorporation of 3.0 wt% of the TiC in the TiO(2) film, the solar-to-electricity conversion efficiency (eta) of the cell reached 7.56% from its value of 6.61% with a bare TiO(2) film. "In situ" incorporation of this TiC/a-TiO(2) composite in the commercial TiO(2) is considered as the basis for enhanced cell efficiency of the benefited cell. The variations in J(SC), FF, and V(OC) are explained by analyzing the data of dark currents, UV-absorption spectra, transparency spectra, and electrochemical impedance spectra (EIS) which were obtained under illumination and darkness. Enhancement in the V(OC) for the promoted cell is explained through pertinent electron lifetime in the TiO(2) film, which was obtained by using laser-induced photo-voltage transient studies. Electron diffusion coefficient was also measured by using laser-induced photo-current transient studies. PMID- 20571618 TI - Local control of multidimensional dynamics. AB - The control of chemical reactions has been a target for researchers since the development of lasers which operated on a timescale fast enough to follow nuclear motion. Since then a number of schemes have been developed, each proving successful in a selection of systems. In this paper we present results obtained following the implementation of local control theory together with the multi configuration time dependent Hartree quantum dynamics algorithm, aiming to efficiently design control pulses for polyatomic systems. Control of multidimensional models of cyclobutadiene and pyrazine are presented and discussed. These results represent a starting point for further studies, showing the distinct advantages of using this approach for controlling chemical reactions. PMID- 20571619 TI - Isolation and characterisation of amphotericin B analogues and truncated polyketide intermediates produced by genetic engineering of Streptomyces nodosus. AB - Amphotericin B is a powerful but toxic drug used against fungal infections and leishmaniases. These diseases would be treated more effectively if non-toxic amphotericin derivatives could be produced on a large scale at low cost. Genetic manipulation of the amphotericin B producer, Streptomyces nodosus, has previously led to the detection and partial characterisation of 8-deoxyamphotericin B, 16 descarboxyl-16-methyl-amphotericin B, 15-deoxy-16-descarboxyl-16-methyl-15-oxo amphotericin B, 7-oxo-amphotericin B and pentaene analogues. Here we report improved production and purification protocols that have allowed detailed chemical analyses of these compounds. The polyketide synthase product 8-deoxy-16 descarboxyl-16-methyl-amphoteronolide B was identified for the first time. In addition, the ketoreductase 10 domain of the polyketide synthase was specifically inactivated by targeted gene replacement. The resulting mutants produced truncated polyketide intermediates as linear polyenyl-pyrones. PMID- 20571620 TI - Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate. AB - The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s( 1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy. PMID- 20571621 TI - A first principles study of water dissociation on small copper clusters. AB - Water dissociation on copper is one of the rate-limiting steps in the water-gas shift (WGS) reaction. Copper atoms dispersed evenly from freshly made catalyst segregate to form clusters under the WGS operating conditions. Using density functional theory, we have examined water adsorption and dissociation on the smallest stable 3-dimensional copper cluster, Cu(7). Water molecules are adsorbed on the cluster sequentially until full saturation at which no direct water-copper contact is sterically possible. The adsorption is driven mainly by the overlap between the p-orbital of O atom occupied by the lone pair and the 3d-orbitals of copper, from which a fractional charge is promoted to the 4s-orbital to accommodate the charge transfer from water. Water dissociation on the Cu(7) cluster was investigated at both low and high water coverage. It was found that water dissociation into OH and H is exothermic but is inherently a high temperature process at low coverage. At high coverage, the reaction becomes more exothermic with fast kinetics. In both cases, water can catalyze the reaction. It was found that direct dissociation of the OH species is endothermic with a significantly higher barrier at both low and high coverage. However, the OH species can readily react with another adjacent hydroxyl group to form an O adatom and water molecule. Our studies indicate that the basic chemical properties of water dissociative chemisorption may not change significantly with the size of small copper clusters. Similarities between water dissociation on copper clusters and on copper crystalline surfaces are discussed. PMID- 20571622 TI - Chemistry, antiproliferative activity and low nephrotoxicity of 3,5-diacetyl 1,2,4-triazol bis(4N-thiosemicarbazone) ligands and their platinum(II) complexes. AB - The preparation and characterization of 3,5-diacetyl-1,2,4-triazol bis(4,4 dimethylthiosemicarbazone) ligand, H(3)L(1), and its dinuclear platinum complex [Pt(mu-HL(1))](2) is described. The crystal and molecular structure of the platinum complex has been resolved by single crystal X-ray diffraction. The ligands coordinate, in an asymmetric dideprotonate form, to the platinum ions in a tridentate fashion (NNS) and S-bridging bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The new compounds synthesized together with the analogous monosubstituted ligand 3,5-diacetyl-1,2,4-triazol bis(4-methylthiosemicarbazone) (H(5)L(2)) and its dinuclear platinum(ii) complex [Pt(mu-H(3)L(2))](2) have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H(3)L(1) and [Pt(mu-H(3)L(2))](2) since they not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. Subsequent nephrotoxic study, in LLC-PK1 cells, show that the four compounds investigated exhibit very low nephrotoxicity with respect to cisplatin. PMID- 20571623 TI - Lanthanide doped silica nanoparticles applied to multiplexed immunoassays. AB - Luminescent samarium (Sm) and europium (Eu) doped silica nanoparticles (SiO(2) NPs) were investigated for use in multiple target immunoassays. Particles with a diameter of 40 +/- 10 nm were synthesized and applied to multiplexed immunoassays in a single well of an assay plate. The luminescent behavior of the lanthanide doped NPs was compared to conventional dyes in solution and in surface confined model immunoassays against two analytes. Luminescence from the dyes and NPs was detected with an imaging spectroscopic system and this could be processed with a simple least squares procedure. In solution, NPs exhibited linear mixing behaviour while conventional fluorescent dyes required careful control to solution conditions, particularly pH. A conventional dye system consisting of FITC and Cy3 applied to a two analyte model system resulted in up to 70% energy transfer from FITC to Cy3 under conditions of high surface coverage. This made quantitative analysis intractable for unknown samples. The lanthanide doped silica nanoparticles responded well to both analytes (<5% relative std. dev.). The results demonstrate that NPs provide alternatives to conventional dyes due to low susceptibility to pH and related solution conditions, absence of energy transfer, single excitation wavelength range, and high stokes shift. These properties allowed quantitative analysis of multiple analytes in the same well. PMID- 20571624 TI - The effect of pressure on the crystal structure of [Gd(PhCOO)3(DMF)]n to 3.7 GPa and the transition to a second phase at 5.0 GPa. AB - The effect of pressure on the crystal structure of the coordination polymer [Gd(PhCOO)(3)(DMF)](n) has been studied to 5.0 GPa. At ambient pressure the structure is tetragonal (space group P4(2)/n) with the polymers extending along the c-direction of the unit cell; successive Gd atoms are alternately bridged by four benzoates and by two benzoates; the coordination spheres of the metal atoms are completed by DMF ligands. This results in two different Gd...Gd repeats, measuring 3.8953(3) and 5.3062(3) A, respectively. The polymer chains interact with each other via dispersion interactions, including a number of CH...pi contacts to phenyl rings in which the H...ring-centroid distances are 3.19 to 3.28 A. Up to 3.7 GPa the crystal remains in a compressed form of its ambient pressure phase. The a-axis shortens by 7.7%, and the c-axis by 2.9%, the difference reflecting the greater ease of compression along the crystallographic directions mediated by weak intermolecular interactions. At ambient pressure the Gd-O distances span 2.290(2)-2.559(2) A, with an average of 2.39(3) A. At 3.7 GPa the corresponding parameters are 2.259(3) to 2.509(4) and 2.36(3) A. The Gd...Gd distances shortened by 0.0467(4) and 0.1851(4) A, and the CH...pi distances span the range 2.76-2.90 A. During compression a number of H...H contacts develop, the shortest measuring 1.84 A at 3.7 GPa. On increasing the pressure to 5.0 GPa a phase transition occurred in which the shortest H...H contact is relieved by conversion of an edge-to-edge phenyl-phenyl contact into a pi...pi stacking interaction. The new phase is also tetragonal, space group P4, the inversion symmetry present in phase-I being lost in phase-II. The phase transition allows more efficient packing of ligands, and while the a-axis decreases in length the c axis increases. This leads to Gd...Gd distances of 3.8373(4) and 5.3694(4) A, the latter being longer than at ambient pressure. Gd-O distances at 5.0 GPa span the range 2.265(5) to 2.516(5) A, with a mean of 2.36(2) A. PMID- 20571625 TI - Platinum-mediated aryl-aryl bond formation and sp(3) C-H bond activation. AB - A novel process is described in which intramolecular oxidative addition is followed by aryl-aryl bond formation and sp(3) C-H bond activation leading to a six-membered platinacycle. PMID- 20571626 TI - Diastereomers of the pentacoordinate chiral phosphorus compounds in solution: absolute configurations and predominant conformations. AB - The absolute structural information about four sets of diastereomers of pentacoordinate spirophosphoranes, derived separately from L (or D)-phenylglycine and L (or D)-phenylalanine, has been obtained by using vibrational circular dichroism (VCD) spectroscopic measurements and density functional theory (DFT) for the first time. Each compound contains a stereogenic centre at the phosphorus center and two at the amino acid ligands. Geometric searches at the B3LYP/6 311++G** level have been performed for all possible low energy conformers whose vibrational absorption (VA) and VCD spectra have also been simulated. The good agreement between the experimental VA and VCD spectra in the dimethyl sulfoxide (DMSO) solution and the simulated ones allows us to assign the absolute configurations and predominant conformations of these pentacoordinate phosphorus compounds with high confidence. Solvent effects have been examined by using both the experimental measurements and theoretical calculations. The implicit continuous polarization model and the explicit solute-solvent intermolecular hydrogen-bonding model have been considered to understand the effects of DMSO on the spectra observed. The influence of basis sets and different functionals on the VA and VCD spectra of this type of coordination compounds has also been investigated. PMID- 20571627 TI - A fully complementary, high-affinity receptor for phosphate and sulfate based on an acyclic tris(urea) scaffold. AB - A fully complementary tris(urea) receptor for phosphate and sulfate anions has been developed by mimicking the scaffold of terpyridine which shows very high affinities and selectivities toward the tetrahedral anions. PMID- 20571633 TI - Conformational behavior of fibrinogen on topographically modified polymer surfaces. AB - The influence of topographical surface features at the submicron scale on the structural changes in the surface-adsorbed fibrinogen was investigated on poly(lactic-co-glycolic-acid) (PLGA) films. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed in this study for the induced conformational change of fibrinogen over various adsorption times, while the adsorption kinetics of fibrinogen was quantified by the enzyme linked immunosorbent assay (ELISA). When a PLGA surface is modified topographically, the adsorbed fibrinogen undergoes less conformational change when compared to adsorption on the pristine PLGA surface. The extent of conformational change is related to platelet adhesion. Reduced thrombogenicity was demonstrated by the higher ratios of alpha-helix to beta-turn and beta-sheet to beta-turn structures on the topographic PLGA film, which suggests that topographical manipulation of surfaces is a viable approach to influence the thrombogenicity of surfaces. PMID- 20571634 TI - One-step growth of high luminescence CdTe quantum dots with low cytotoxicity in ambient atmospheric conditions. AB - A simple, rapid, cost-efficient and convenient method has been developed for synthesis of water-soluble CdTe quantum dots (QDs) under ambient atmospheric conditions. Using this method, the preparation of Te precursor and growth of CdTe QDs were achieved with one-step synthetic route. Under the optimal conditions, the as-prepared CdTe QDs possessed a high photoluminescence quantum yield (84%), a narrow size distribution (full width at half maximum = 30 nm), small particle size (2.6 nm) and low cytotoxicity. The photoluminescence and electrogenerated chemiluminescence (ECL) behaviors of as-prepared CdTe QDs show their potential application in cell imaging and ECL biosensing with high sensitivity. PMID- 20571635 TI - Clickable peptide nucleic acids (cPNA) with tunable affinity. AB - Peptide nucleic acids (PNAs) are functional analogues of natural oligonucleotides. Herein, we report the synthesis of PNAs bearing a triazole in lieu of the amide bond assembled using a "click" cycloaddition, their hybridization properties as well as the DNA-templated coupling of the azide and alkyne PNA fragments. PMID- 20571636 TI - Functional monolayers on oxide-free silicon surfaces via thiol-ene click chemistry. AB - Thiol-ene click chemistry was used for the attachment of a variety of functional molecules onto oxide-free Si(111) surfaces using very mild conditions; the efficient nature of this coupling strategy allowed for successful light-induced micropatterning and thus provides a novel route towards biofunctional electronics. PMID- 20571637 TI - Cubic spinel In4SnS8: electrical transport properties and electrochemical hydrogen storage properties. AB - In this work, electrical transport properties and electrochemical hydrogen storage properties of a cubic spinel In(4)SnS(8) hierarchical nanostructure were investigated. A simple single layer device exhibits non-linear current-voltage (I V) characteristics. The detailed electrical transport properties of the sample indicated that the conduction mechanism varied in different external voltage regions. Derived from the typical spinel system of the A[B(2)]X(4) (A: Zn, Cu, Sn, B: In, Ga, X: S, Se) ternary chalcogenides, this thiospinel compound also shows high electrochemical hydrogen storage of 127 mAh g(-1) and its mechanism is discussed. PMID- 20571638 TI - Correlation of photophysical parameters with macrocycle distortion in porphyrins with graded degree of saddle distortion. AB - Different porphyrin conformations are believed to play a role in controlling the cofactor properties in natural tetrapyrrole-protein complexes. In order to study the correlation between macrocycle nonplanarity and physicochemical properties in detail, a series of six porphyrins with graded degree of macrocycle distortion was investigated. These conformationally designed porphyrins are based on the successive introduction of beta-ethyl groups into the tetraphenylporphyrin parent macrocycle and the degree of nonplanarity is dependent on the number and localization of the beta-ethyl meso-phenyl interactions. The electronic properties of the complete series of porphyrins were investigated in solution. It was found that the singlet and triplet properties depend not only on the out-of plane distortion parameter but also on the type of central metal. Moreover, it was found that macrocycle distortion affects the singlet state properties significantly stronger than the triplet properties. In addition, the efficiency of energy transfer to molecular oxygen was investigated. It was shown that the singlet oxygen quantum yield depends strongly on the triplet state lifetime of the porphyrins, resulting in differences between the decrease of intersystem crossing and singlet oxygen quantum yield. The observed gradual change of electronic parameters of base free tetraphenylporphyrins with increasing deformation of the macrocycle indicates the validity of using conformationally designed porphyrins to fine-tune photophysical properties. PMID- 20571642 TI - Synthesis and properties of functional oxynitrides--from photocatalysts to CMR materials. AB - Oxynitrides constitute a vast class of emerging solids to explore new or improved properties analogous to those of oxides. In this perspective we will show recent developments in this area, discussing different groups of structures and materials such as colossal magnetoresistive (CMR), pigments, phosphors, photocatalysts for water splitting and organic molecule degradation, dielectrics, and anodes for lithium batteries, in connection with their preparative methods and crystal chemistry. PMID- 20571643 TI - Use of plasma-activated gases in synthesis of solid-state nitrides. AB - Basic properties of the plasma state are summarized, with the emphasis on low pressure, non-isothermal, and cold plasma. The advantages of plasma activation in the synthesis of solid-state materials, especially nitrides, are discussed. PMID- 20571644 TI - Increasing the dimensionality of hybrid vanadium oxyfluorides using ionothermal synthesis. AB - A unique organically-templated vanadium(IV) oxyfluoride, [pyH][V(2)O(2)F(5)] has been prepared using an ionothermal approach. This compound has a novel layered structure which may be considered as arising via condensation of previously known 'ladder-like' structural building units. This suggests that ionothermal synthesis may provide a more effective route to extended network structures in these systems than the more widely explored hydrothermal-based media. PMID- 20571645 TI - One-step synthesis of high-purity fluorous-capped inorganic nanoparticles. AB - Making use of the fact that perfluorohydrocarbon, and hydrocarbon solvents become miscible at high temperatures, highly pure inorganic nanoparticles capped with fluorous labels have been generated in a one-step synthesis. The procedure involves taking the reactants in a hydrocarbon+perfluorohydrocarbon mixture along with a fluorous reagent and carrying out the reaction at elevated temperatures. On cooling the reaction mixture, fluorous-capped inorganic nanoparticles dispersed in the perfluorohydrocarbon are obtained. PMID- 20571646 TI - Anionic templating in a new layered bismuth tellurium oxychloride, Bi3Te4O10Cl5. AB - A new layered bismuth tellurium oxychloride, Bi(3)Te(4)O(10)Cl(5) has been synthesized by a solid-state reaction under vacuum using Bi(2)O(3), TeO(2), and TeCl(4) as reagents. The structure of Bi(3)Te(4)O(10)Cl(5) has been determined by single-crystal X-ray diffraction. Bi(3)Te(4)O(10)Cl(5) contains two different lone pair cations, Bi(3+) and Te(4+) that are in asymmetric coordination environments. Bi(3)Te(4)O(10)Cl(5) has a novel two-dimensional layered structure consisting of distorted BiO(4)Cl(2) octahedra, BiO(4)Cl(3) polyhedra, TeO(4) polyhedra, and isolated Cl(-) ions. Complete structural analysis, infrared spectrum, thermogravimetric analysis, and dipole moment calculations are presented. Crystal data: Bi(3)Te(4)O(10)Cl(5), monoclinic, space group C2/m (No. 12), a = 15.372(3) A, b = 4.1004(7) A, c = 13.301(2) A, beta = 98.336(5) degrees, V = 829.5(2) A(3), and Z = 2. PMID- 20571647 TI - One-step hydrothermal coating approach to photocatalytically active oxide composites. AB - Three-dimensional Bi(2)WO(6)/TiO(2) hierarchical heterostructures with secondary anatase TiO(2) nanoparticles grown on primary Bi(2)WO(6) microspheres have been successfully obtained by a low temperature hydrothermal method. The hierarchical Bi(2)WO(6)/TiO(2) structures displayed significantly enhanced visible-light driven photocatalytic activity in comparison to isolated Bi(2)WO(6) microspheres and TiO(2) nanoparticles. Furthermore, this methodology is of general interest, because it can be used to fabricate other oxide heterostructures, such as BiVO(4)/TiO(2) and Bi(2)MoO(6)/TiO(2). PMID- 20571648 TI - Novel ternary alkaline-earth and rare-earth metal antimonides from gallium or indium flux. Synthesis, structural characterization and 121Sb and 151Eu Mossbauer spectroscopy of the series A7Ga8Sb8 (A = Sr, Ba, Eu) and Ba7In8Sb8. AB - Reported are the synthesis and the structural characterization of the new ternary antimonides Eu(7)Ga(8)Sb(8), Sr(7)Ga(8)Sb(8), Ba(7)Ga(8)Sb(8), and Ba(7)In(8)Sb(8). They have been synthesized from reactions of the corresponding elements, using gallium or indium as metal fluxes. The four compounds are isostructural and crystallize with the space group P6(3)/mmc (no. 194) with lattice parameters as follows: a = 4.4942(8), c = 17.274(6) A for Eu(7)Ga(8)Sb(8); a = 4.5409(8), c = 17.486(4) A for Sr(7)Ga(8)Sb(8); a = 4.7045(12), c = 18.123(9) A for Ba(7)Ga(8)Sb(8); and a = 4.8274(3), c = 18.421(2) A for Ba(7)In(8)Sb(8). The temperature dependence of the magnetic susceptibility of Eu(7)Ga(8)Sb(8) confirms that the Eu ions are in the typical divalent state (Eu(2+)) with a room temperature effective magnetic moment mu(eff) = 8.02 mu(B). A phase transition from a paramagnetic to an antiferromagnetically ordered structure occurs in this material below 6 K. These results are corroborated by (151)Eu Mossbauer spectroscopy at 4.2 and 78 K, respectively. Eu(7)Ga(8)Sb(8), Ba(7)In(8)Sb(8) and the previously reported Sr(7)Ga(2)Sb(6) derivative of the cubic Th(3)P(4) type, were also investigated by (121)Sb Mossbauer spectroscopy. PMID- 20571649 TI - Synthesis of CuAl2(acac)4(O(i)Pr)4, its hydrolysis and formation of bulk CuAl2O4 from the hydrolyzed gels; a case study of molecules to materials. AB - CuAl(2)(acac)(4)(O(i)Pr)(4) was obtained by the reaction driven by the ligand rearrangement between anhydrous Cu(acac)(2) and Al(OPr(i))(3) in toluene under refluxing conditions. The single molecular nature and the stability of the precursor were evidenced by the presence of the molecular ion peak at m/z 749 in the EI mass spectrum. The FT-IR spectrum also confirmed the formation of the molecular precursor with strong bands appearing at 961, 1021, 1289, 1394, 1527 and 1594 cm(-1). Very low solubility as well as low stability of the precursor in common solvents hindered the growth of single crystals. The stability could be improved in acetic acid medium which was further used for the controlled hydrolysis of the precursor. A blue gel obtained on hydrolysis for 11 days showed the presence of acetate, isopropoxy and acac moieties in addition to the hydroxide group in the FT-IR spectrum. Fast hydrolysis assisted by ultrasonication with 1.5 ml of the hydrolyzing agent for 6 h resulted in a blue colored gel, the FT-IR spectrum of which also indicated the presence of acetate, isopropoxy, acac and hydroxide moieties. Both the gels showed a mass loss up to 78% according to thermal analysis in air up to 900 degrees C. While the PXRD pattern of the gel from the controlled hydrolysis yielded monophasic cubic CuAl(2)O(4) on heating at 900 degrees C in air for 12 h, phase pure product could be obtained within 12 h at 700 degrees C from the sonicated gel. Both the oxides were nanosized as observed in the TEM images. The particle size distribution obtained from the laser light scattering method showed monodispersity. The room temperature Raman spectrum of CuAl(2)O(4) exhibited broad bands at 476, 505, 610, 712, 792 cm(-1) typical of nanosized crystallites and were assigned based on group theoretical analysis. The (27)Al NMR spectrum of CuAl(2)O(4) showed a sharp and intense resonance signal at around delta = 0.112 ppm characteristic of aluminium in octahedral coordination and one sharp signal at delta = 69 ppm corresponding to tetrahedrally coordinated aluminium. Heterogeneous catalytic reduction of p-nitrophenol using CuAl(2)O(4) was followed by UV/visible spectroscopy. CuAl(2)O(4) from the present procedure proved to be an effective catalyst for the reduction of p-nitrophenol. PMID- 20571650 TI - Topotactic reduction as a synthetic route for the preparation of low-dimensional Mn(II) oxide phases: the structure and magnetism of LaAMnO(4-x) (A = Sr, Ba). AB - Reaction of LaSrMnO(4) with CaH(2) at 420 degrees C yields LaSrMnO(3.67(3)). Raising the temperature to 480 degrees C yields the Mn(II) phase LaSrMnO(3.50(2)). Neutron powder diffraction data show both phases adopt body centred orthorhombic crystal structures (LaSrMnO(3.67(3)), Immm: a = 3.7256(1) A, b = 3.8227(1) A, c = 13.3617(4) A; LaSrMnO(3.50(2)), Immm: a = 3.7810(1) A, b = 3.7936(1) A, c = 13.3974(3) A) with anion vacancies located within the equatorial MnO(2-x) planes of the materials. Analogous reactivity is observed between LaBaMnO(4) and CaH(2) to yield body-centred tetragonal reduced phases (LaBaMnO(3.53(3)), I4/mmm: a = 3.8872(1)A, c = 13.6438(2) A). Low-temperature neutron diffraction and magnetisation data show that LaSrMnO(3.5) and LaBaMnO(3.5) exhibit three-dimensional antiferromagnetic order below 155 K and 135 K respectively. Above these temperatures, they exhibit two-dimensional antiferromagnetic order with paramagnetic behaviour observed above 480 K in both phases. The origin of the low dimensional magnetic order and ordering of the anion vacancies in the reduced phases is discussed. PMID- 20571651 TI - Preparation of gallium oxynitride powder and its nanofibers by the nitridation of a gallium oxide precursor doped with nickel or cobalt obtained via the citrate route. AB - Acicular crystals were grown in gallium oxynitride powder prepared by ammonia nitridation of amorphous gallium oxide precursors containing less than 5 at% of either Ni or Co, via the citrate route. The crystals were several tens of nanometres wide, several micrometres long, and grown in the temperature range 750 to 850 degrees C in a flow of ammonia of less than 200 mL min(-1). The crystal structure of the gallium oxynitride was a highly disordered 2H wurtzite-type with some 3C zinc blende-type stacking faults. The crystals grew in their basal plane changing their aspect ratio with the supplying method of small amounts of Ni or Co and an amount of residual carbon. The acicular crystals were grown by the catalytic behavior of Ni or Co to enhance one-dimensional growth in the hexagonal c-plane. PMID- 20571652 TI - Porous lanthanide oxides via a precursor method: morphology control through competitive interaction of lanthanide cations with oxalate anions and amino acids. AB - Porous lanthanide oxides were fabricated by a precursor-thermolysis method. The precursors were synthesized by a hydrothermal reaction with lanthanide (La, Ce, Pr and Nd) salts, sodium oxalate and asparagine (or glutamine). Under hydrothermal conditions asparagine and glutamine exhibited greatly different complexation abilities with lanthanide cations. The competitive interactions of lanthanide cations with oxalate anions and asparagine (or glutamine) gave rise to the formation of precursors with different structures and morphologies. ESI-MS detection further confirmed the different complexation abilities of asparagine or glutamine with lanthanide cations at the molecular level. Variation of oxalate anion concentration or the pH value of the reaction solution could tune the morphology of the products. After calcination, porous lanthanide oxides were obtained with the morphologies of their corresponding precursors. Our work suggests that the complexation ability of organic molecules with metal cations could be a crucial factor for morphological control of the precursors. Moreover, considering the diversity of organic additives and metal salts, other metal oxides with complex composition and morphology could be fabricated via this organic molecule-modified precursor method. PMID- 20571667 TI - Semiconducting polymers: the Third Generation. AB - There has been remarkable progress in the science and technology of semiconducting polymers during the past decade. The field has evolved from the early work on polyacetylene (the First Generation material) to a proper focus on soluble and processible polymers and co-polymers. The soluble poly(alkylthiophenes) and the soluble PPVs are perhaps the most important examples of the Second Generation of semiconducting polymers. Third Generation semiconducting polymers have more complex molecular structures with more atoms in the repeat unit. Important examples include the highly ordered and crystalline PDTTT and the ever-growing class of donor-acceptor co-polymers that has emerged in the past few years. Examples of the latter include the bithiophene-acceptor co polymers pioneered by Konarka and the polycarbazole-acceptor co-polymers pioneered by Leclerc and colleagues. In this tutorial review, I will summarize progress in the basic physics, the materials science, the device science and the device performance with emphasis on the following recent studies of Third Generation semiconducting polymers: stable semiconducting polymers; self-assembly of bulk heterojunction (BHJ) materials by spontaneous phase separation; bulk heterojunction solar cells with internal quantum efficiency approaching 100%; high detectivity photodetectors fabricated from BHJ materials. PMID- 20571668 TI - Carbazole-based polymers for organic photovoltaic devices. AB - Polymers based upon 2,7-disubstituted carbazole have recently become of great interest as electron-donating materials in organic photovoltaic devices. In this tutorial review the synthesis of such polymers and their relative performances in such devices are surveyed. In particular structure-property relationships are investigated and the potential for the rational design of materials for high efficiency solar cells is discussed. In the case of the 2,7-carbazole homopolymer it has been found that electron acceptors other than fullerenes produce higher energy conversion efficiencies. To get around possible problems with the build-up of charge density at the 3- and 6-positions and to improve the solar light harvesting ability of the polymers by reducing the bandgap, ladder- and step ladder type 2,7-carbazole polymers have been synthesised. The fully ladderised polymers gave very poor results in devices, but efficiencies of over 1% have been obtained from a step-ladder polymer with a diindenocarbazole monomer unit. Donor acceptor copolymers containing 2,7-carbazole donors and various electron accepting comonomer units have been prepared. An efficiency of 6% has been reported from a device using such a copolymer and by suitable choice of the acceptor comonomer, polymers can be designed with potential theoretical power conversion efficiencies of 10%. While such efficiencies remain to be obtained, the results to date certainly suggest that carbazole-based polymers and copolymers are among the most promising materials yet proposed for obtaining high efficiency organic solar cells. PMID- 20571670 TI - Conducting supramolecular nanofibers and nanorods. AB - Recent progress in the study of electroconducting nanomaterials such as nanofibers, nanorods and other nanostructures based on the supramolecular self assembly of hexabenzocoronenes, oligo(thiophene)s, tetrathiafulvalenes and perylene-3,4,9,10-tetracarboxylic diimides is described in this tutorial review. Conducting nanofibers and nanorods are constructed by doping pi-donors or pi acceptors with oxidants or reductants before/after the formation of such nanostructures; however, some nanofibers show electric conductivity without any doping in the neutral state. Although cation radicals and anion radicals seem to be difficult to form nanofibers and nanorods, a limited number of cation radicals produce conducting nanofibers. For nanofibers and nanorods composed of weak pi donors and pi-acceptors, their conductivities are measured by time-resolved microwave conductivity techniques. PMID- 20571669 TI - Water-soluble fluorescent conjugated polymers and their interactions with biomacromolecules for sensitive biosensors. AB - Over the past decades, water-soluble conjugated polymers (CPs) have gained increasing attention as optical platforms for sensitive detection of biomacromolecules (DNA, protein and cell) due to the amplification of fluorescent signals. To meet the requirement for high throughput assays, chip and microarray techniques based on CPs have also been developed. Very recently, fluorescence imaging in vivo and at the cellular level have also been successfully accomplished using these water-soluble CPs. In this tutorial review, we provide a brief review of the synthesis and optical properties of CPs, focusing especially on their applications in biosensors and cell imaging. PMID- 20571671 TI - From helical polyacetylene to helical graphite: synthesis in the chiral nematic liquid crystal field and morphology-retaining carbonisation. AB - This tutorial review presents current progress in the synthesis of helical polyacetylene (H-PA) using a chiral nematic liquid crystal reaction field as an asymmetric polymerisation solvent. In addition, we review the morphology retaining carbonisation for helical graphite using H-PA as a carbonisation precursor. Carbonisation of H-PA films, via iodine doping, is demonstrated to produce carbon and graphitic films bearing completely preserved morphologies and even helical nanofibril structures. PMID- 20571672 TI - Water/alcohol soluble conjugated polymers as highly efficient electron transporting/injection layer in optoelectronic devices. AB - Water/alcohol soluble conjugated polymers (WSCPs) can be processed from water or other polar solvents, which offer good opportunities to avoid interfacial mixing upon fabrication of multilayer polymer optoelectronic devices by solution processing, and can dramatically improve charge injection from high work-function metal cathode resulting in greatly enhancement of the device performance. In this critical review, the authors provide a brief review of recent developments in this field, including the materials design, functional principles, and their unique applications as interface modification layer in solution-processable multilayer optoelectronic devices (135 references). PMID- 20571673 TI - Click polymerization. AB - The development of new polymerization reactions is of critical importance to macromolecule science. In this critical review, we summarize the research efforts to incubate alkyne-azide click reactions into a versatile polymerization technique for the synthesis of poly(triazole)s (PTAs) with linear and hyperbranched structures. Cu(I)- and Ru(II)-catalyzed click polymerizations afforded 1,4- and 1,5-regioregular PTAs, respectively. Whereas traditional thermal cycloadditions normally generate regiorandom products, PTAs with 1,4 regioisomer contents up to 95% were created by utilizing the electronic effect involved in the thermal click polymerizations of aroylacetylenes with azides. The PTAs showed unique functional properties, such as luminescence, chromism, fluorescence imaging, emission superquenching, chain helicity, optical nonlinearity, light refractivity, photovoltaic effect, cytocompatibility and biodegradability (145 references). PMID- 20571677 TI - Direct measurement of salt-mineral repulsion using atomic force microscopy. AB - The disjoining pressure between a mineral and soluble salt crystal in concentrated aqueous solution has been successfully measured with atomic force microscopy. PMID- 20571676 TI - Multiple fluorescent chemical sensing and imaging. AB - Optical sensors, unlike most others, enable multiple sensing of (bio)chemical species by making use of probes whose signals can be differentiated by spectral and/or temporal resolution. Multiple sensors are of substantial interest for continuous monitoring of chemical parameters in complex samples such as blood, bioreactor fluids, in the chemical industry, aerodynamic research, and when monitoring food quality control, to mention typical examples. Moreover, such sensors enable non-invasive, non-toxic and online detection. We discuss in this critical review the state of the art in terms of spectroscopic principles, materials (mainly indicator probes and polymers), and give selected examples for dual and triple sensors along with a look into the future (109 references). PMID- 20571678 TI - Homogeneous iron complexes for the conversion of dinitrogen into ammonia and hydrazine. AB - One of the most challenging problems in small molecule activation is the development of a homogeneous catalyst for converting dinitrogen into ammonia at ambient temperatures and atmospheric pressure. A catalytic cycle based on molybdenum that converts dinitrogen into ammonia has been reported. However, a well defined iron based system for the conversion of dinitrogen into ammonia or hydrazine has remained elusive, despite the relevance of iron to biological nitrogen fixation. In recent years several research groups have made significant progress towards this target. This tutorial review provides a brief historical perspective on attempts to develop iron based catalysts for dinitrogen functionalisation and then focuses on recent breakthroughs in the chemistry of coordinated dinitrogen, such as the generation of ammonia and hydrazine from coordinated dinitrogen, the isolation and characterisation of several proposed intermediates for ammonia generation and some preliminary mechanistic conclusions. PMID- 20571679 TI - The effects of side chain hydrophobicity on the denaturation of simple beta hairpins. AB - To investigate the sequence dependence in the molecular mechanism of urea induced denaturation, molecular dynamics denaturing simulations of two beta-hairpin peptides, a fast folding peptide 1 (SESYINPDGTWTVTE) and a slow folding TRPZIP4 (GEWTWDDATKTWTWTE), were performed in urea aqueous solutions. It was found that beta-hairpin denaturation by urea is highly dependent on the hydrophobicity of the side chains. The two beta-hairpin peptides studied here and the GB1 studied previously display three different denaturant processes in urea solution by which the breaking of backbone native hydrogen bonds takes different orders. The variation of their denaturing mechanism is well correlated to the variation in their structural properties. In peptide 1, which has only a loosely packed hydrophobic core formed by residues Trp11 and Ile5, all backbone native hydrogen bonds (1 to 5) are broken in a short period of time. Whereas for TRPZIP4 with a compact hydrophobic core of four tryptophan residues, the backbone native hydrogen bonds (1 to 6) are considerably more stable, with the middle hydrogen bonds protected well by the hydrophobic core being the most stable. The comparison of different beta-hairpin peptides shows that the side-chain packing on each face of the strands plays a major role in the stability of the backbone native hydrogen bonds in urea solution, and indicates that protein denaturation by urea can be highly sequence dependent. PMID- 20571680 TI - Singlet oxygen: there is indeed something new under the sun. AB - Singlet oxygen, O(2)(a(1)Delta(g)), the lowest excited electronic state of molecular oxygen, has been known to the scientific community for approximately 80 years. It has a characteristic chemistry that sets it apart from the triplet ground state of molecular oxygen, O(2)(X(3)Sigma), and is important in fields that range from atmospheric chemistry and materials science to biology and medicine. For such a "mature citizen", singlet oxygen nevertheless remains at the cutting-edge of modern science. In this critical review, recent work on singlet oxygen is summarized, focusing primarily on systems that involve light. It is clear that there is indeed still something new under the sun (243 references). PMID- 20571681 TI - First principles study of doped carbon supports for enhanced platinum catalysts. AB - Highly oriented pyrolytic graphite (HOPG) implanted with N, Ar and B is studied as a support for platinum nanoparticle catalysts for fuel cells. Experimentally, we find that Pt supported by N-HOPG is more disperse, more catalytically active and suffers less particle ripening than native HOPG, while Pt supported on Ar irradiated HOPG is slightly more active but ripens more than Pt on native HOPG. Defective HOPG supports are modeled by density functional theory (DFT) calculations that confirm and explain the above experimental results. First, defect energetics are studied to demonstrate that nitrogen doping at high doses likely causes agglomerated nitrogenous defect clusters, and irradiation with Ar ions creates vacancies that agglomerate in vacancy clusters. Second, Pt catalyst particle nucleation and agglomeration is studied. For Pt clusters supported on HOPG with nitrogen defects, calculations show a greater driving force for nucleation and greater particle tethering. For Pt clusters supported on HOPG with vacancy aggregations, this study shows a strong driving force for nucleation and a much enhanced tendency for particle ripening. Third, the electronic structure of Pt clusters on different supports is calculated. Finally, reaction energetics are calculated for two likely reaction pathways over Pt clusters supported on different HOPG substrates. Pt-N-HOPG shows modified electronic structure of the Pt catalyst and increased activity towards oxygen. Pt-Ar-HOPG shows slightly enhanced catalytic activity towards oxygen. In all respects, the findings agree with experiment. The calculations attribute the catalytic activity changes primarily to changes in the workfunction and secondarily to the d-band structure of supported Pt particles. PMID- 20571682 TI - Synthesis of linked half sandwich rare-earth metal chlorido and borohydrido complexes and their catalytic behavior towards MMA polymerization. AB - A series of rare-earth metal complexes attached by an amino-functionalized cyclopentadienyl ligand (C(5)Me(4)H-C(6)H(4)-o-NMe(2)) (1) was prepared. The metathesis reaction of the ligand lithium salt [C(5)Me(4)-C(6)H(4)-o-NMe(2)]Li with LnCl(3)(THF)(n) afforded the dichlorido complexes [(C(5)Me(4)-C(6)H(4)-o NMe(2))(2)Ln(2)Cl(4)][LiCl(THF)(2)] (Ln = Y (2a), Lu (2b)), which are trinuclear connected by mu(3)-Cl and mu(2)-Cl multiple bridges. The straightforward metathesis reaction of Ln(BH(4))(3)(THF)(n) with equimolar [C(5)Me(4)-C(6)H(4)-o NMe(2)]Li in THF medium yielded the first linked half sandwich ligand stabilized THF-free rare-earth metal bis(borohydrido) complexes (C(5)Me(4)-C(6)H(4)-o NMe(2))Ln(BH(4))(2) (Ln = Sc (3a), Sm (3b)), respectively. The single component borohydrido complex 3a showed high activity towards the bulk polymerization of methyl methacrylate without specific control, which showed high iso-selectivity (mm = 80%) when the polymerization was performed in benzene medium, and switched to syndio-selectivity (rr = 74% at -20 degrees C) in polar THF medium, whilst the metal chlorido species was inert. The binary catalyst system of 3a/Mg(n)Bu(2) had similar catalytic performances when compared with 3a in THF medium, but provided enriched syndio-control in benzene solution that was in contrast to the iso control of 3a. Surprisingly, 3a upon activation with (n)BuLi displayed an extremely high activity (1.1 x 10(6) g mol(Sc)(-1) h(-1)) and afforded syndiotactic PMMA (rr = 75%) at low polymerization temperature (-20 degrees C) in THF. PMID- 20571683 TI - Chirality of and gear motion in isopropyl methyl sulfide: A Fourier transform microwave study. AB - Isopropyl methyl sulfide (CH(3))(2)CHSCH(3) was investigated by Fourier transform microwave spectroscopy. Two rotational isomers gauche and trans were detected. The rotational spectra of gauche were found fit to an asymmetric rotor pattern, except for being split by the internal rotation of CH(3) attached to S with the potential barrier V(3) of 601.642 (65) cm(-1) and for exhibiting the effect of tunneling between the two equivalent gauche forms in a few high-K transitions. The tunneling was discussed from a viewpoint of chirality. The trans spectra appeared generally similar to those of gauche, with V(3) to the S-CH(3) internal rotation of 559.00 (11) cm(-1), but satellite lines accompanied the ground torsional state lines in some high-K transitions. These satellites were ascribed to the excited state of the C(isop)-S torsion. In fact, the potential function for this torsion was shown by an ab initio calculation to be flat or even of double minima around the trans position, which was presumably caused by a gear coupling between the two methyl groups of the isopropyl group and the one in the S-CH(3). PMID- 20571684 TI - Controlled synthesis of mononuclear or binuclear aryloxo ytterbium complexes supported by beta-diketiminate ligand and their activity for polymerization of epsilon-caprolactone and L-lactide. AB - The reaction of monomeric [(DIPPh)(2)nacnac]YbCl(2)(THF)(2) ((DIPPh)(2)nacnac = N,N-diisopropylphenyl-2,4-pentanediimineanion) with NaOAr (OAr = 2,6 diisopropylphenoxide) in THF afforded the mononuclear complexes [(DIPPh)(2)nacnac]Yb(OAr)Cl(THF) 1 and [(DIPPh)(2)nacnac]Yb(OAr)(2) 2 depending on the molar ratio of dichloride to sodium salt, while the same reaction with NaOAr' (OAr' = 2,6-dimethylphenoxide) in toluene yielded the binuclear complex [{(DIPPh)(2)nacnac}Yb(OAr')](2)(mu-Cl)(2) 3. Treatment of [(DIPPh)(2)nacnac]Yb(THF)(mu-Cl)(3)Yb(Cl)[(DIPPh)(2)nacnac] with NaOAr and NaOAr', respectively, in toluene yielded selectively the corresponding binuclear complexes {[(DIPPh)(2)nacnac]Yb(OAr)(mu-Cl)(3)Yb[(DIPPh)(2)nacnac](THF)} 4 and {[(DIPPh)(2)nacnac]Yb(OAr')(mu-Cl)(3)Yb[(DIPPh)(2)nacnac](THF)} 5 in high yields. All complexes were structurally characterized. Complex 2 was found to be a highly active initiator for both polymerizations of epsilon-caprolactone (epsilon-CL) and L-lactide. All monoaryloxide complexes can initiate the polymerization of epsilon-CL in a controlled manner giving polymers with narrow molecular weight distributions (M(w)/M(n) around 1.06) with relatively low activity relative to complex 2. PMID- 20571685 TI - Theoretical study of the mechanisms of the hydrolysis and condensation reactions of silicon and titanium alkoxides: similarities and differences. AB - Stationary states for hydrolysis reactions in M(OCH(3))(4) + nH(2)O (M = Si, Ti; n = 1-3) systems are optimized at the B3LYP and MP2 levels with the Wachters basis set for titanium and the cc-pVDZ set for other atoms. Geometries of these states for M = Ti are characterized by trigonal bipyramidal (water molecules in front-side position) and octahedral coordination (for back-side position). Barrier heights for hydrolysis and condensation are substantially lower than those for silicon in keeping with experimental results. The lowering of the barrier heights on the addition of water molecules in the front-side position (reduction of hydrogen bond strain) exceeds that of the back-side addition (catalytic effect) for both M = Si and Ti, but the difference diminishes with n. The influence of oligomerization of titanium alkoxides on the rate of hydrolysis is studied on the model of the interaction of a Ti(2)(OCH(3))(8) dimer with one and two water molecules. It was shown that only terminal methoxy groups are exposed to hydrolysis and therefore the dimeric structure is retained in the process of the substitution of terminal methoxy groups. Barrier heights for terminal hydrolysis do not differ significantly from those of monomers. Barrier heights for condensation reactions obtained for the 2M(OMe)(n)(OH)(4-n) + H(2)O model system, are substantially (by ca. 10 kcal mol(-1)) lower for M = Ti and in both silicon and titanium species demonstrate a steady growth with n. PMID- 20571687 TI - Aryne-mediated syntheses of structurally related acene derivatives. AB - Cycloaddition reactions of tetrakis(hexyloxy)-substituted 2,3-triphenylyne (2,3 didehydrotriphenylene) provide straightforward access to three new cata-condensed polyarenes characterized by the presence of 5, 8 and 11 fused benzene rings. PMID- 20571686 TI - Fluorescence and chemiluminescence properties of indolylmaleimides: experimental and theoretical studies. AB - Various indolylmaleimides (IMs) were synthesized, and their fluorescence (FL) and chemiluminescence (CL) were measured. The substitution at the 2-position of the indole ring and the 3- or 4-position of the maleimide moiety caused an obvious change in the FL and CL of the IMs. An almost on-off switching of the FL of the IMs was observed. The intramolecular charge transfer from the indole moiety to the maleimide moiety occurred in 3-(1H-3-indolyl)-2,5-dihydro-1H-2,5 pyrroledione. In the FL of the IMs, CASPT2 calculations showed deprotonation of the NH group of the indole ring and the maleimide moiety at the excited state. The C[double bond, length as m-dash]C bond in the maleimide moiety was needed for strong CL in the IMs without substitution at the 2-position of the indole ring. The relationships between the FL or CL properties and the structures of the IMs were clarified. These results provide significant information on the rational design of IMs as FL and CL probes. PMID- 20571688 TI - An improved version of the Kornyshev-Eigen-Wicke model for the diffuse double layer in concentrated electrolytes. AB - The Kornyshev-Eigen-Wicke model for the diffuse double layer in concentrated electrolytes has been improved in two ways. First, the role of the compressibility factor a(0) has been included in the expressions for the electrochemical potentials of the component ions. As a result this quantity also appears in the equations for the potential drop across the diffuse layer, and its differential capacity. Second, an estimate is made of the ion atmosphere effect using the reciprocal of the thickness of the ionic atmosphere. It is shown that these changes result in considerable improvement in the estimates of the diffuse layer potential drop and differential capacity on the basis of Monte Carlo data. PMID- 20571689 TI - Microfluidic dissolved oxygen gradient generator biochip as a useful tool in bacterial biofilm studies. AB - A microfluidic chip for generation of gradients of dissolved oxygen was designed, fabricated and tested. The novel way of active oxygen depletion through a gas permeable membrane was applied. Numerical simulations for generation of O(2) gradients were correlated with measured oxygen concentrations. The developed microsystem was used to study growth patterns of the bacterium Pseudomonas aeruginosa in medium with different oxygen concentrations. The results showed that attachment of Pseudomonas aeruginosa to the substrate changed with oxygen concentration. This demonstrates that the device can be used for studies requiring controlled oxygen levels and for future studies of microaerobic and anaerobic conditions. PMID- 20571690 TI - Catalysis and the nature of mixed-metal oxides at the nanometer level: special properties of MO(x)/TiO(2)(110) {M= V, W, Ce} surfaces. AB - To rationalize structure-reactivity relationships for mixed-metal oxide catalysts, well-defined systems are required. Studies involving the deposition of nanoparticles and clusters of VO(x), CeO(x) and WO(x) on TiO(2)(110) and other well-defined oxide surfaces have shown novel structures that have special chemical properties. Dimers of vanadia and ceria have been found on TiO(2)(110), monomers of vanadia on CeO(2)(111), and (WO(3))(3) clusters on TiO(2)(110). The V[double bond, length as m-dash]O or W[double bond, length as m-dash]O groups present in VO(x)/TiO(2)(110), VO(x)/CeO(2)(111) and WO(x)/TiO(2)(110) surfaces dislay a very high activity for the selective oxidation of alkanes and the dehydrogenation of alcohols. The non-typical coordination modes imposed by TiO(2)(110) on ceria nanoparticles make possible the direct participation of this oxide in catalytic reactions and enhance the dispersion of metals on the titania substrate. Au/CeO(x)/TiO(2)(110) surfaces display an extremely high catalytic activity for CO oxidation and the water-gas shift reaction. In general, the chemical behavior of the MO(x)/TiO(2)(110) {M = V, Ce or W} surfaces reflects their unique structure at the nanometer level. These simple models can provide a conceptual framework for modifying or controlling the chemical properties of mixed-metal oxides and for engineering industrial catalysts. PMID- 20571691 TI - Miniaturized system for isotachophoresis assays. AB - We present an inexpensive hand-held device (240 g) that implements microchip isotachophoresis (ITP) with laser induced fluorescence (LIF) detection. This self contained instrument integrates the functionality required for high voltage generation onto a microelectronic chip, includes LIF detection and is powered by a universal serial bus (USB) link connected to a laptop computer. Using this device we demonstrate focusing and detection of a fluorescent species with a limit of detection of 100 pM. We show that the response of the detector is linear with the initial analyte concentration, making this device suitable for quantitative analysis. We also demonstrate the use of our simulation tools for design and prediction of ITP assays, and validate these results with a demonstration of multiplexed indirect detection of (unlabeled) analytes performed using the device. We find good agreement between simulations and experimental results. Using a label-free isotachaphoresis assay implemented in the hand-held device we detect two explosives and an endocrine disruptor spiked in river water, with no prior sample processing. PMID- 20571692 TI - Halogen bonding: an electrostatically-driven highly directional noncovalent interaction. AB - A halogen bond is a highly directional, electrostatically-driven noncovalent interaction between a region of positive electrostatic potential on the outer side of the halogen X in a molecule R-X and a negative site B, such as a lone pair of a Lewis base or the pi-electrons of an unsaturated system. The positive region on X corresponds to the electronically-depleted outer lobe of the half filled p-type orbital of X that is involved in forming the covalent bond to R. This depletion is labeled a sigma-hole. The resulting positive electrostatic potential is along the extension of the R-X bond, which accounts for the directionality of halogen bonding. Positive sigma-holes can also be found on covalently-bonded Group IV-VI atoms, which can similarly interact electrostatically with negative sites. Since positive sigma-holes often exist in conjunction with negative potentials on other portions of the atom's surface, such atoms can interact electrostatically with both nucleophiles and electrophiles, as has been observed in surveys of crystallographic structures. Experimental as well as computational studies indicate that halogen and other sigma-hole interactions can be competitive with hydrogen bonding, which itself can be viewed as a subset of sigma-hole bonding. PMID- 20571695 TI - New intramolecular through-space charge transfer emission: tunable dual fluorescence of terfluorenes. AB - We have synthesized a series of new terfluorene derivatives, and investigated their novel fluorescence emission behaviors. We have demonstrated a new intramolecular through-space charge transfer emission experimentally and theoretically. This is the first report on spiroconjugation-like caused fluorescence emission, which could be tuned by the electron nature of pendent groups without changing their absorption. PMID- 20571694 TI - A method to site-specifically introduce methyllysine into proteins in E. coli. AB - A mutant pyrrolysyl-tRNA synthetase/tRNA pair was used to genetically encode allylcarbamoyl methyllysine in bacteria. This amino acid can be converted to methyllysine with a ruthenium catalyst, providing a straightforward approach for site-specifically introducing methyllysine residues into proteins. PMID- 20571696 TI - Zeta potential based colorimetric immunoassay for the direct detection of diabetic marker HbA1c using gold nanoprobes. AB - A one-step homogeneous colorimetric immunoassay format coupled with zeta potential measurements for determination of specific diabetic biomarker glycated hemoglobin (HbA1c) using functionalised gold nanoparticles as bioprobes is reported. The assay exhibited an excellent sensitivity based on absorbance and zeta potential measurements showing the dynamic response range from 0.001-0.004 mg mL(-1) for HbA1c with a detection limit of 0.0015 mg mL(-1). PMID- 20571697 TI - "Clickable" polymer nanoparticles: a modular scaffold for surface functionalization. AB - The versatility of copper-catalyzed alkyne-azide coupling (CuAAC) in functionalizing drug-loaded polymer nanoparticles is demonstrated via the modification of surfaces of acetylene-functionalized PNPs with folate, biotin, and gold nanoparticles. PMID- 20571698 TI - Metal trifluoromethanesulfonate-catalyzed regioselective acylation of myo inositol 1,3,5-orthoformate. AB - A highly regioselective acylation of myo-inositol 1,3,5-orthoformate at the 4-O/6 O positions is catalyzed by various metal trifluoromethanesulfonates, giving excellent yields; an asymmetric example using (-)-camphanic anhydride is described here. PMID- 20571699 TI - Local structure investigation of oxide ion and proton defects in Ge-apatites by pair distribution function analysis. AB - In this communication we provide a direct insight into the local structure and defects of oxygen excess Ge-apatites, in both dry and deuterated states, by means of pair distribution function analysis. PMID- 20571700 TI - Novel nanowire array based highly efficient quantum dot sensitized solar cell. AB - In this communication, a novel CdSe/CdS/ZnO nanowire array fabricated by a 3-step solution-based method was used as a photoanode of a quantum dot sensitized solar cell, which generated a maximum power conversion efficiency of 4.15%. PMID- 20571701 TI - Green synthesis and potential application of low-toxic Mn : ZnSe/ZnS core/shell luminescent nanocrystals. AB - A microwave-assisted synthetic procedure is presented for the preparation of low toxic Mn:ZnSe/ZnS core/shell nanocrystals to label antibodies for selective detection of human immunoglobulin G (IgG) based on fluorescence resonance energy transfer (FRET) between the Mn:ZnSe/ZnS and Au nanoparticles (AuNPs). PMID- 20571702 TI - High electrocatalytic activity of tethered multicopper oxidase-carbon nanotube conjugates. AB - Multicopper oxidases linked to multiwall carbon nanotubes via the molecular tethering reagent, 1-pyrenebutanoic acid, succinimidyl ester, displayed high bioelectrocatalytic activity for oxygen reduction. PMID- 20571703 TI - Conversion of nonporous helical cadmium organic framework to a porous form. AB - Two novel cadmium-organic frameworks containing achiral helical nanotubular channels, [Cd(HImDC)(S)](n) (S = Im(1) and Py(2)), have been synthesized and characterized using single crystal X-ray diffraction, in which 1 converts to 2 upon refluxing 1 in pyridine solution with noticeable porosity and hydrogen uptake at medium pressure. PMID- 20571704 TI - Control over the permeation of silica nanoshells by surface-protected etching with water. AB - We demonstrate a water-based etching strategy for converting solid silica shells into porous ones with controllable permeability. It overcomes the challenges of the alkaline-based surface-protected etching process that we previously developed for the production of porous and hollow silica nanostructures. Mild etching around the boiling point of water partially breaks the imperfectly condensed silica network and forms soluble monosilicic acid, eventually producing mesoscale pores in the silica structures. With the surface protection from poly(vinyl pyrrolidone) (PVP), it is possible to maintain the overall shape of the silica structures while at the same time to create porosity inside. By using bulky PVP molecules which only protect the near-surface region, we are able to completely remove the interior silica and produce hollow particles. Because the etching is mild and controllable, this process is particularly useful for treating small silica particles or core-shell particles with very thin silica shells for which the alkaline-based etching method has been difficult to control. We demonstrated the precise control of the permeation of the chemical species through the porous silica shells by using a model reaction which involves the etching of Ag encapsulated inside Ag@SiO(2) by a halocarbon. It is expected that the water based surface-protected etching method can be conveniently extended to the production of various porous silica shells containing functional materials whose diffusion to outside and/or reaction with outside species can be easily controlled. PMID- 20571705 TI - Stabilisation of liquid-air surfaces by particles of low surface energy. AB - We describe the stabilisation of liquid-air surfaces by microparticles of a low surface energy solid. By varying the surface tension of the liquid, various particle-stabilised materials from oil dispersions to air-in-oil foams to dry water can be prepared. PMID- 20571706 TI - Reactivity of an aryl-substituted silicon-silicon triple bond: 1,2-disilabenzenes from the reactions of a 1,2-diaryldisilyne with alkynes. AB - The reactivity of a diaryl-substituted disilyne, Ar-Si[triple bond, length as m dash]Si-Ar, with alkynes was examined. Reaction of the disilyne with acetylene yielded a 1,2-disilabenzene as the sole product. PMID- 20571707 TI - Chiral cyclotrisiloxanes. AB - We have synthesized and separated the enantiomer pair of chiral cyclotrisiloxanes for the first time. Three-blade propeller-like alignment of three phenyl groups in tri(2-butyl)triphenylcyclotrisiloxane induced a positive Cotton effect with (R)-2-butyl group, and a negative effect with (S)-2-butyl substituent. PMID- 20571708 TI - Structural and electronic trends in rare-earth technetate pyrochlores. AB - We report the structures and electronic properties of nine novel rare earth technetate pyrochlores with ideal stoichiometry Ln(2)Tc(2)O(7) (Ln = Ce-Pm, Gd, Tb, Ho, Tm, Lu) predicted within the framework of gradient-corrected density functional theory. The computed structures of Er(2)Tc(2)O(7), Dy(2)Tc(2)O(7), and Sm(2)Tc(2)O(7) also closely match available X-ray diffraction data. PMID- 20571709 TI - Catalytic water oxidation on derivatized nanoITO. AB - Electrocatalytic water oxidation occurs on high surface area, nanocrystalline ITO (nanoITO) surface-derivatized by phosphonate-binding of the catalyst [Ru(Mebimpy)(4,4'-((HO)(2)OPCH(2))(2)bpy)(OH(2))](2+) (Mebimpy is 2,6-bis(1 methylbenzimidazol-2-yl)pyridine; bpy is 2,2'-bipyridine). With nanoITO, spectral data can be acquired on electrochemically generated intermediates and voltammograms monitored spectrophotometrically. PMID- 20571710 TI - A ligand-chirality controlled supramolecular hydrogel. AB - We report a novel example of ligand-chirality finely controlled in situ supramolecular hydrogel formation based on the coordination of phenylalanine (Phe) to Cu(II) with higher selectivity over other metal ions. As decreasing both enantiomeric excesses (ee%) of ligand Phe towards its D- and L-forms, the gelation ability of Phe-Cu(II) supramolecular metallogelator was found to be weakened and eventually disappeared, which likely resulted from the stereoselectivity of the ligand Phe. Intermolecular hydrogen bonding, hydrophobic and/or pi-pi stacking interactions were also found to be essential for forming the metallogel. We believe that the present work can open up a new entry for developing novel and promising chiral sensing and recognition platforms, i.e. visually sensing chiral molecules by naked eyes due to the feature of a sol-to gel transition induced smartly by varying the ligand chirality. PMID- 20571711 TI - Organically-templated Kagome compounds containing two transition metal ions. AB - Kagome compounds containing two transition metal ions, Co(II) and Ni(II), in different proportions have been synthesized, and their magnetic properties have been found to exhibit interesting differences. PMID- 20571712 TI - Photoprotection by carotenoid pigments in the yeast Rhodotorula mucilaginosa: the role of torularhodin. AB - In this paper we report the relationship between carotenoids and ergosterol and cell UV-B resistance in different strains of the yeast Rhodotorula mucilaginosa. Cell survival was studied using a set of 13 strains; additionally, two mutants (a hyper-producing one and a colourless one) in combination with diphenylamine (DPA), a carotenogenesis inhibitor, were used. A positive correlation between total carotenoids and survival to UV-B radiation was found. However, when individual carotenoid concentrations were tested, only torularhodin was found to be significantly related to UV-B survival. On the contrary, ergosterol did not affect survival. The hyper-pigmented strain showed an enhanced survival (up to 250%) compared to the parental strain, while the survival of the albino mutant was similar to that experienced by the parental strain; however, observed changes in survival were dose dependent. The cyclobutane pyrimidine dimers (CPDs), one of the major forms of DNA damage caused by UV exposure, appears as unrelated to the accumulation of carotenoids and cell survival. These results indicate that bearing higher torularhodin concentrations enhances UV-B survival in yeasts and, thus, the accumulation of this pigment constitutes an important mechanism that improves the resistance of yeasts to UV-B. PMID- 20571714 TI - [Speak of open access?]. PMID- 20571713 TI - Investigation on the phototransformation of tadalafil in aqueous media. 6 Epimerization vs. solvent trapping reaction. AB - Irradiation of tadalafil at lambda > 290 nm in aqueous solutions leads to 6 epimer and/or water adducts depending on concentration and pH. A rationalization of the results involves the heterolytic cleavage of C6-N5 bond via a well stabilized zwitterionic intermediate. The drug is stable in the dark except under strongly basic conditions where it undergoes C12a-epimerization. PMID- 20571715 TI - [The ethical aspects of population screening programme of rare diseases]. AB - The Committee on Ethics of the Instituto de Investigacion de Enfermedades Raras (CEIIER) of the Spanish National Institute of Health Carlos III, presents this article dealing with ethical guidelines regarding the implementation of screening population programmes with special emphasis on genetic screening. After a critical review it has been addressed 24 recommendations concerning 14 topics: evaluation of the opportunity of the programme, including ethical analysis besides scientific evidences and cost/benefits issues; the need to differentiate between research and public health intervention and to built a specific and comprehensive programme; the creation of an interdisciplinary working group which control its implementation and prepare a protocol including justification, development, therapeutic or preventive actions and follow-up activities; the review of the programme by an independent Ethical committee; the guarantee of the voluntary, universal and equitable population access, which requires sufficient information on the programme and their specific relevant facts, as incidental detection of heterozygous state in minors in newborn screening and the relevance of non directive genetic counselling specially in prenatal screening offered to pregnant women; considerations regarding future uses of samples for research purposes; total quality and periodic programme evaluation; guarantee of personal data confidentiality and the conflict of interest statement of the members of all the Committees involved in the programme. PMID- 20571716 TI - [Heat health warning systems: possibilities of improvement]. AB - In the summer of 2003 the temperatures reached were responsible for a large number of deaths in Europe. A year after this fact, many countries had implemented some sort of plan of prevention against excessive temperatures. Plans that had already shown its ability to prevent a large proportion of avoidable mortality in other latitudes. Since then, a lot of papers have been published providing new data on health effects of a heat wave, which can help increase the efficiency of these prevention plans. Knowing the weather conditions at risk, defining "heat wave" or to take into account the time that the plan should be active from the study of the relationship between temperature and their effects on health, to identify weather patterns that modulate the relationship between temperature and mortality, locate the profile of people at risk or to develop protocols for action as accurately as possible and based on scientific knowledge are elements drawn from studies carried on in recent years that should be taken into account. PMID- 20571717 TI - [Physical fitness enhancement through education, EDUFIT study: background, design, methodology and dropout analysis]. AB - Physical fitness is a powerful marker of cardiovascular health already at early stages in life. To promote physical fitness enhancement from the school is therefore needed. The present study describes a school intervention program specifically designed for these purposes, called EDUFIT (EDUcation for FITness). The study was carried out in 2007 and comprised 67 adolescents aged 13+/-1 years from a secondary school who belonged to three different classes. The classes were randomly allocated to control group (CG), experimental group 1 (EG1) and experimental group 2 (EG2). The CG was involved in 2 physical education sessions/week, the EG1 was involved in 4 physical education sessions/week (volume increased) and the EG2 was involved in 4 physical education sessions/week of high intensity (volume+intensity increased). Several health parameters were assessed before and after a 16-weeks intervention: physical fitness, body composition, lipid-metabolic profile, ventilatory parameters, blood pressure, and cognitive and academic performance. The intervention was feasible and well-tolerated. There were high participation and adherence rates, i.e. 96% (n=67) and 84% (n=56) respectively. Yet not always significant (0,1>P>0,05), we observed that the adolescents who satisfactory complete the program showed better cognitive and academic performance, and worse levels of adiposity, diastolic tension, handgrip strength and maximal expiratory pressure. The hypothesis of the EDUFIT study is that to double the number of physical education classes will improve physical fitness in adolescents. The confirmation of the hypothesis could have important public health implications. PMID- 20571718 TI - [Quality of life, health and well-being conceptualizations from the perspective of the International Classification of Functioning, disability and health (ICF)]. AB - The World Health Organization's International Classification of Functioning, Disability and Health (ICF) has provided a new foundation for our understanding of health, functioning, and disability. As a content-valid, comprehensive and universally applicable health classification, it serves as a platform to clarify and specify health-related concepts that are frequently used in the medical literature as well-being, health state, health status, quality of life (QoL) and health-related quality of life (HRQoL). The ICF entities health and health related domains and functioning will be used as starting point to reach the objective of the paper. Health domains refer to domains intrinsic to the person as a physiological and psychological entity. Health-related domains are not part of a person's health but are so closely related that a description of a person's lived experience of health would be incomplete without them. Functioning refers to all health and health-related domains within the ICF. Well-being is made up of health, health-related, and non-health-related domains, such as autonomy and integrity. QoL is the individual's perceptions of how the life is going in health, health-related, and non-health domains. HRQoL is the individual's perceptions of how the life is going in health and health-related domains. "HRQoL is to QoL as functioning is to well-being". The ICF represents a standardized and international basis for the operationalization of health based on its health domains, and is also the basis for the operationalization of functioning based on all health and health-related domains contained therein. The authors argue that functioning is an operationalization of health from a broader perspective that consider the individual person not only as a biological but also as a social entity. PMID- 20571719 TI - [Cardiovascular prevention according to CEIPC: a critical appraisal]. AB - We present a critical appraisal of the adaptation to the 4th European Guidelines on Cardiovascular Disease Prevention in Clinical Practice carried out by The Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention (CEIPC), which is based on: 1) the removal, by the CEIPC, of important restrictions on the start of drug therapy that are contained in the European guide 2) the existence of internal contradictions and differing recommendations regarding the goals of LDL in the several publications of the CEIP adaptation; and 3) and the almost total lack of necessary discussion about risk tables in Spain. Therefore, it makes a critical appraisal of some of the most important clinical recommendations shared by the CEIPC and the European guide that are not supported by clinical evidence, like the implicit proposal of using the estimated cardiovascular risk as a target for treatment, the criteria to begin the antihypertensive drug therapy and therapeutic goals for blood pressure, LDL cholesterol and HbA1c. The public health administration and also the scientific society must ensure transparency and independence in the drafting of documents endorsed by them, including the management and declaration of potential conflicts of interest among editors and group members. The public health administration and also the scientific society must guarantee a framework of honesty and transparency in the documents endorsed by them, with a complete declaration of the authors conflict of interests. PMID- 20571720 TI - [Measles outbreak in Campo de Gibraltar, Cadiz, Spain, during the Period February July 2008]. AB - BACKGROUND: On the 4th of February 2008, 2 cases of measles, epidemiologically linked (2 members of the crew of the Fast-Ferry Jaime I from the company Balearia, which performs the route Algeciras-Tangier), were notified to the Epidemiological Surveillance Network in Andalusia (SVEA). The aim of this paper is to epidemiologically characterize this population level outbreak detected in the area of Campo de Gibraltar, the vaccine effectiveness and the control measures implemented. METHODS: Descriptive observational study of reported cases. We have analysed the following variables: age, sex, municipality of residence, onset date, virus genotype, groups involved, previous immunization status, interventions, vaccine effectiveness. Information sources are SVEA records, vaccination program and individual digital story (Diraya). Rates 10(5) were calculated according to age group and frequency measurements. To compare vaccine effectiveness, the Chi(2) test was used. RESULTS: We confirmed 155 cases of measles, 88.4% by laboratory techniques. Most affected age groups under 2 years (19%) and from 21 to 40 (51%). The 54.2% male. The 72,14% were not vaccinated. Virus was isolated from imported measles genotype D4. The vaccine efficacy was greater than 99%. CONCLUSIONS: The outbreak of the imported measles virus was confirmed. More than half of the cases were not vaccinated. The decrease in the incidence in vaccinated individuals recommends the necessity of carrying out Catch-Up campaigns to increase the coverage therefore avoiding the appearance of these outbreaks. PMID- 20571721 TI - [Abdominal girth utility as a method of metabolic syndrome screening in people with hypertension]. AB - BACKGROUND: The most useful criteria for diagnosis of the Metabolic Syndrome (MS) are those proposed by the ATP-III from NCEP 2001, reviewed in 2005. Waist circumference is one of the criteria included in the ATP-III estimate. Given the high incidence of coronary disease attributable to this risk factor, it seems interesting to evaluate its performance as an isolated parameter for the screening of MS among people with a variety of other prevalent cardiovascular risk factors, such as high blood pressure. METHODS: DESIGN: case-control study. Cases were defined as patients with hypertension and MS. Controls were those patients with hypertension and without MS. SAMPLE: the entire population attended in a Primary Care area that had, unless one blood analysis performed between July first 2007 and December 31st 2007. SAMPLE size: 137 individuals were included (60 cases and 77 controls). STATISTICAL ANALYSIS: test of logistical regression was used to estimate of the probability of suffering from MS according to values of waist circumference. RESULTS: Probability of MS among hypertensive patients = 1/ (1+2,718281828-(-10+ (perimeter x 0,097))). Probability of MS among female hypertensive patients = 1/(1+2,718281828-(-10+ (perimeter x 0,099))). Probability of MS among male hypertensive patients = 1/(1 +2,718281828-(-10+ (perimeter x 0,105))). CONCLUSIONS: Among hypertensive patients, MS can be predicted by means of a formula (calculator), which takes waist circumference as unique variable. This method can be used to better stratify patients according to their cardiovascular risk and to identify those who need an early preventive intervention. We propose a table with the calculations already made. PMID- 20571722 TI - [Changes in tobacco consumption among workers in Spain since the law 28/2005, health measures against smoking]. PMID- 20571723 TI - [Microsurgical treatment of internal carotid bifurcation aneurysms]. AB - Clinical and imaging findings of a series of 14 internal carotid artery bifurcation aneurysms microsurgically treated are presented. A total of 10 lesions were diagnosed before rupture and 4 patients presented with subarachnoidal hemorrhage and frontobasal intracerebral bleeding. Diagnosis was done using neuroimaging (CT scan, angio-CT-3D, angio-MRI, angiography) but patients with ruptured aneurysms were treated with the sole information provided by the angio-CT-3D. The average fundus size was 8.4mm (3-13.3) and the average neck size was 6.8mm (3-9.6), being the fundus-to-neck ratio 1.32 (0.46-2.05). All lesions were microsurgically treated through a pterional approach with the help of temporary clipping of the afferent vessels in all cases. We used peroperative neuroprotective, neuromonitorization and micro-doppler cerebral flow measurement. Clinical results were excellent with 13 patients GOS grade 5 and one grade 4 three month afterwards of hospital discharge and complete exclusion of the lesion in angiographic controls done solely in patients with ruptured lesions. PMID- 20571724 TI - [Analysis of early tracheostomy and its impact on development of pneumonia, use of resources and mortality in neurocritically ill patients]. AB - OBJECTIVE: We analyze the most suitable time to perform tracheostomy in neurocritically ill patients. We compare morbimortality and use of resources between those patients in which tracheostomy was done early (9 days), in a selected group of patients. MATERIAL AND METHODS: We made an observational prospective study involving a group of patients diagnosed as traumatic brain injury (TBI) or stroke, whose tracheostomy was performed during their stay at the Intensive Care Unit. We compared two groups: a) early tracheostomy (during first 9 days of ICU stay); b) late tracheostomy (made on 10th day or later). As variables, we studied: demographic data, severity of illness at admission, admittance department, diagnosis, length of intubation, length of mechanical ventilation (LMV), sedation and antibiotic treatment needs, ventilator-associated pneumonia (VAP) events, ICU length of stay and mortality. We calculated relative risk of suffering from pneumonia and made a multivariate logistic regression to establish which factors were associated with an increased risk of developing pneumonia. Statistical signification p Hg > Pb > Cu > Zn > As. Meanwhile, sediment contamination level had been obviously decreasing before the storing water of Three Gorge Reservoir. PMID- 20571759 TI - Assessment of 20 organochlorine pesticides (OCPs) pollution in suburban soil in Tianjin, China. AB - Soil contamination with organochlorine pesticides has aroused worldwide concerns considering their high toxicities and long-term persistence. In this study, 87 representative soil samples from suburban areas (Xiqing, Dongli, Jinnan, Beichen) of Tianjin, the third biggest city in China, were collected to evaluate the pollution of 20 organochlorine pesticides. Surface soil samples were air-dried and sieved. Ultrasonic extraction was used for organochlorine pesticides preparation prior to analysis with gas chromatography-mass spectrometry. It was revealed that p,p'-DDE, p,p'-DDD, o,p'-DDT, o,p'-DDD, hexachlorobenzene, dicofol and beta-HCH were seven pesticides detected most frequently. DDTs, HCHs and hexachlorobenzene were the predominant pesticide pollutants in soil. Spatial variation of these organochlorine pesticides in soil was illustrated; Pollution levels, characteristics and possible sources were also investigated. Most of other 13 kinds of pesticides were detected and the frequencies of detection were calculated to reveal the pollution status, which ranged from 0.0% (aldrin, dieldrin and endrin) to 34.5% (p,p'-DDT). These data were helpful to figure out the pollution of organochlorine pesticides and could be further used to evaluate the health risk associated with soil pollution. PMID- 20571760 TI - Levels of organochlorine pesticide residues in blood plasma of various species of birds from India. AB - Concentrations of organochlorine pesticides (OCPs) were measured in blood plasma of 13 species of birds collected from Ahmedabad, India. Among the various OCPs determined, HCHs and its isomers had higher contribution to the total OCPs. Concentration of summation operatorHCHs varied from 11.4 ng/mL in White ibis Threskiornis melanocephalus to 286 ng/mL in Sarus Crane Grus antigone, while summation operatorDDT ranged between 19 ng/mL in Black Ibis Pseudibis papillosa and 147 ng/mL in Painted Stork Mycteria leucocephala. p,p'-DDE was accounted for more than 50% of total DDT in many of the samples analysed. However, a p,p'-DDT to p,p'-DDE ratio higher than one obtained for many species of birds indicates the recent use of DDT in this study region. The concentrations of cyclodiene insecticides, heptachlor epoxide, dieldrin and total endosulfan ranged from 15.8 to 296.2 ng/mL, below detectable level to 15 and 41.1-153.2 ng/mL, respectively. The pattern of total OCP load generally occurred in the following order: granivores < insectivores < omnivores < piscivores < carnivores. Although, the organochlorine residues detected in blood plasma of birds are not indicative of toxicity, the presence of residues in birds over the years (2005-2007) indicates continued exposure to organochlorine compounds. However, continuous monitoring is recommended to facilitate the early identification of risks to the survival of a species. PMID- 20571761 TI - Polycyclic aromatic hydrocarbons in superficial sediments from Ghar El Melh lagoon, Tunisia. AB - The concentrations of 17 polycyclic aromatic hydrocarbons (PAHs) were determined in 12 superficial sediments collected from the Ghar El Melh lagoon. Sediment samples were extracted by Soxhlet, and analyzed by Gas chromatography with flame ionisation detector (FID). PAH concentrations, ranged from 39.59 to 655.28 ng/g on a dry weight. Total PAH concentrations were not correlated with organic carbon (OC) content or grain size (% <63 microm). Special PAH compound ratios, such as Ft/Py and Ft/Ft + Py were calculated to evaluate different hydrocarbon origins and showed that PAHs are derived from pyrolytic process. PMID- 20571762 TI - Assessment of contamination of soil due to heavy metals around coal fired thermal power plants at Singrauli region of India. AB - In the present study, an attempt was made to measure contamination of soil around four large coal-based Thermal Power Plants. The concentration of Cadmium, Lead, Arsenic and Nickel was estimated in all four directions from Thermal Power Plants. The soil in the study area was found to be contaminated to varying degrees from coal combustion byproducts. The soil drawn from various selected sites in each direction was largely contaminated by metals, predominantly higher within 2-4 km distance from Thermal Power Plant. Within 2-4 km, the mean maximum concentration of Cadmium, Lead, Arsenic and Nickel was 0.69, 13.69, 17.76, and 3.51 mg/kg, respectively. It was also observed that concentration was maximum in the prevalent wind direction. The concentration of Cadmium, Lead, Arsenic and Nickel was highest 0.69, 13.23, 17.29 and 3.56 mg/kg, respectively in west direction where wind was prevalent. PMID- 20571763 TI - Clinical outcome after reconstruction for isolated posterior cruciate ligament injury. AB - Fifty-one patients were operated with reconstruction for an isolated PCL injury from 1997 to 2005. Forty-three of these patients were followed during a median period of 48 months (17-109). Median time from injury to surgery was 18 months (2 368). Five patients were operated within the first 6 months after the injury. Nineteen patients had a BPTB autograft, 24 had a hamstring tendon autograft, and seven patients in the hamstring group had a double-bundle femoral fixation. Clinical assessment included Lysholm knee score, International Knee Documentation Committee 2000 (IKDC) scores, Cincinnati score, Tegner score, KOOS score, VAS score, stress radiographs, and a functional test. The median Lysholm score at follow-up was 80 (32-95). Median Tegner score before injury was 7 (1-10) and at follow-up 6 (0-9). Median Cincinnati and IKDC 2000 scores were 74 (12-100) and 63 (24-100), respectively. The mean VAS for subjective assessment of knee function was 67.6 (SD = 22.9). The radiologically measured difference in posterior tibial translation between operated and non-injured knees was mean 8.4 mm (SD =4.8). Four different functional tests showed function of the operated leg from 92% (25 128) to 95% (15-124) compared to the opposite leg. This study shows good functional outcome after reconstruction for isolated rupture of the posterior cruciate ligament. However, pain and instability are still a problem, as only three patients reported full Lysholm subscore indicating full stability, and only four patients reported full subscore indicating no knee pain. PMID- 20571765 TI - Long-term lower urinary tract dysfunction after radical hysterectomy in patients with early postoperative voiding dysfunction. PMID- 20571764 TI - Long-term outcome of transurethral injection of hyaluronic acid/dextranomer (NASHA/Dx gel) for the treatment of stress urinary incontinence (SUI). AB - INTRODUCTION AND HYPOTHESIS: To investigate the long-term safety and efficacy of transurethral injection of NASHA/Dx gel in women suffering from stress urinary incontinence (SUI). METHODS: Women with SUI treated with NASHA/Dx gel via the transurethral Implacer device at Mayday University Hospital between November 2002 and December 2003 had long-term outcomes of therapy evaluated. RESULTS: Eighteen of 21 were followed-up at mean 6.7 years (+/-SD 0.15). One year after the injection, 11/21 (52.3%) reported improvement. Of the women, 6/21 (28.5%) had a repeat injection and seven (33.3%) women experienced adverse events in the form of periurethral swellings. At 6.7 years, only one of seven women was continent of urine without requiring any further continence procedure, 44.4% were still experiencing SUI symptoms. Nine of 18 (42.8%) had undergone other continence procedures. CONCLUSION: Transurethral injection of NASHA/Dx gel in women with SUI is associated with complications and not effective in the long term. PMID- 20571766 TI - Labial fusion causing urinary incontinence and recurrent urinary tract infection in a postmenopausal female: a case report. AB - A 73-year-old postmenopausal woman was admitted with recurrent urinary tract infection and a history of incontinence. General physical examination was normal. Complete labial fusion was noticed on genital examination. Surgical intervention was performed. This therapy alleviated incontinence and recurrent urinary tract infection. PMID- 20571767 TI - Proteomic analysis of pubocervical fascia in women with and without pelvic organ prolapse and urodynamic stress incontinence. AB - INTRODUCTION AND HYPOTHESIS: This pilot study compares protein expression patterns in the pubocervical fascia of women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI) and asymptomatic women with normal pelvic support. METHODS: Samples of pubocervical fascia were collected from four women with POP and SUI and from three asymptomatic (control) women. These were analyzed using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The expression levels of transgelin, smooth muscle gamma-actin, myosin light polypeptide 6, and alpha-1 antitrypsin precursor were more than twofold higher in patients than in controls. An additional five proteins were overexpressed (more than twofold) in patients, while three proteins were detected only in the patients. CONCLUSION: This pilot study is the first study to estimate changes in protein expression in the pubocervical fascia of human patients with POP. These changes could be related to the pathophysiology of POP. PMID- 20571768 TI - Resolution of right ureteral lesion after subtotal hysterectomy due to benign pathology. A clinical case study. AB - INTRODUCTION: Ureteral lesion during gynecological surgery to correct benign uterine pathology is around 0.03-2.0%, and usually occurs at the ligature of blood vessels. CLINICAL CASE HISTORY: At the end of 3 months, the patient does not manifest any symptoms and does exhibit a good bilateral renal function. Ureteral lesions resulting from gynecological surgery represent a medico-legal problem, which is not a negligible issue for the current healthcare system, so it is necessary to conduct a correct pre-operative and intra-operative assessment to prevent such lesions. DISCUSSION: We describe here the case story of a 40-year old female patient, who, after subtotal hysterectomy for myomas, presented with acute abdominal pain, and was diagnosed with a right ureteral lesion, via CAT imaging; the patient received direct ureterovesical implantation of double J catheter, which was kept in place for 8 weeks. PMID- 20571769 TI - Increasing adherence with the use of hip protectors for older people living in the community. AB - For people at high risk of hip fracture living in community settings, providing hip protectors at no cost increased adherence, but the additional effect of an educational programme was limited. Overall, the level of adherence was modest. INTRODUCTION: The objective of the study was to increase adherence with hip protector use by older people at high risk of hip fracture. The study included two randomised controlled trials with 308 older people recruited from three hospital rehabilitation wards and 171 older people recruited from the community. METHODS: Participants were randomised into three groups. The control group received a brochure about hip protectors. The no cost group were fitted with free hip protectors and asked to use them. The combined group received free hip protectors and education sessions about their use. Adherence with the use of hip protectors at 3 and 6 months after recruitment was measured. Secondary outcomes were falls, fractures and hospitalisations. RESULTS: Very few participants in the two control groups bought a hip protector. Overall adherence in the four intervention groups was modest, but higher in the community recruitment setting (49%) than in the hospital recruitment setting (36%) at 6 months. In the community recruitment group, at 3 months of follow-up, a significantly higher number of participants in the combined group (62%) were wearing hip protectors compared to the no cost group (43%, p=0.04). Five hip fractures occurred during the study, with four sustained whilst not wearing the hip protectors. CONCLUSION: Providing hip protectors at no cost to community living older people at high risk of hip fractures modestly increases initial acceptance and adherence with hip protector use. Additional education may further increase hip protector use in people living in the community in the short term. PMID- 20571770 TI - Fracture risk in children with a forearm injury is associated with volumetric bone density and cortical area (by peripheral QCT) and areal bone density (by DXA). AB - Children who sustain a forearm fracture when injured have lower bone density throughout their skeleton, and have a smaller cortical area and a lower strength index in their radius. Odds ratios per SD decrease in bone characteristics measured by peripheral quantitative computed tomography (pQCT) and dual-energy X ray absorptiometry (DXA) were similar (1.28 to 1.41). INTRODUCTION: Forearm fractures are common in children. Bone strength is affected by bone mineral density (BMD) and bone geometry, including cross-sectional dimensions and distribution of mineral. Our objective was to identify bone characteristics that differed between children who sustained a forearm fracture compared to those who did not fracture when injured. METHODS: Children (5-16 years) with a forearm fracture (cases, n = 224) and injured controls without fracture (n = 200) were enrolled 28 +/- 8 days following injury. Peripheral QCT scans of the radius (4% and 20% sites) were obtained to measure volumetric BMD (vBMD) of total, trabecular and cortical bone compartments, and bone geometry (area, cortical thickness, and strength strain index [SSI]). DXA scans (forearm, spine, and hip) were obtained to measure areal BMD (aBMD) and bone area. Receiver operating characteristic (ROC) analyses were used to assess screening performance of bone measurements. RESULTS: At the 4% pQCT site, total vBMD, but not trabecular vBMD or bone area, was lower (-3.4%; p = 0.02) in cases than controls. At the 20% site, cases had lower cortical vBMD (-0.9%), cortical area (-2.8%), and SSI ( 4.6%) (p < 0.05). aBMD, but not bone area, at the 1/3 radius, spine, and hip were 2.7-3.3% lower for cases (p < 0.01). Odds ratios per 1 SD decrease in bone measures (1.28-1.41) and areas under the ROC curves (0.56-0.59) were similar for all bone measures. CONCLUSIONS: Low vBMD, aBMD, cortical area, and SSI of the distal radius were associated with an increased fracture risk. Interventions to increase these characteristics are needed to help reduce forearm fracture occurrence. PMID- 20571771 TI - Socioeconomic status and bone health in community-dwelling older men: the CHAMP Study. AB - SUMMARY: The association between socioeconomic status (SES) and bone health, specifically in men, is unclear. Based upon data from the large prospective Concord Health in Ageing Men Project (CHAMP) Study of community-dwelling men aged 70 years or over, we found that specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, reflected bone health in older Australian men. INTRODUCTION: Previous studies reported conflicting results regarding the relationship between SES and bone health, specifically in men. The main objective of this study was to investigate associations of SES with bone health in community-dwelling men aged 70 years or over who participated in the baseline phase of the CHAMP Study in Sydney, Australia. METHODS: The Australian Socioeconomic Index 2006 (AUSEI06) based on the Australian and New Zealand Standard Classification of Occupations was used to determine SES in 1,705 men. Bone mineral density and bone mineral content (BMC) were determined by dual energy X-ray absorptiometry. Bone-related biochemical and hormonal parameters, including markers of bone turnover, parathyroid hormone, and vitamin D, were measured in all men. RESULTS: General linear models adjusted for age, weight, height, and bone area revealed no significant differences across crude AUSEI06 score quintiles for BMC at any skeletal site or for any of the bone-related biochemical measures. However, multivariate regression models revealed that in Australian-born men, marital status was a predictor of higher lumbar BMC (beta = 0.07, p = 0.002), higher total body BMC (beta = 0.05, p = 0.03), and lower urinary NTX-I levels (beta=-0.08, p = 0.03), while living alone was associated with lower BMC at the lumbar spine (beta=-0.05, p = 0.04) and higher urinary NTX I levels (beta=0.07, p = 0.04). Marital status was also a predictor of higher total body BMC (beta = 0.14, p = 0.003) in immigrants from Eastern and South Eastern Europe. However, in immigrants from Southern Europe, living alone and acculturation were predictors of higher femoral neck BMC (beta = 0.11, p = 0.03) and lumbar spine BMC (beta = 0.10, p = 0.008), respectively. CONCLUSIONS: Although crude occupation-based SES scores were not significantly associated with bone health in older Australian men, specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, were predictors of bone health in both Australia-born men and European immigrants. PMID- 20571772 TI - Do RANKL inhibitors (denosumab) affect inflammation and immunity? AB - Receptor activator of nuclear factor kappa B ligand (RANKL) and its natural antagonist, osteoprotegerin (OPG), are, respectively, an indispensable factor and a potent inhibitor for osteoclast differentiation, activity, and survival. The development of a human monoclonal antibody to RANKL, denosumab, constitutes a novel approach to prevent fragility fractures in osteoporosis, skeletal complications of malignancy, and potentially bone erosions in rheumatoid arthritis (RA). In addition to being expressed by osteoblasts, RANKL is abundantly produced by activated T cells, and synoviocytes in RA, whereas its receptor, RANK, is also expressed by monocytes/macrophages and dendritic cells. However, in preclinical and clinical studies of RA-including patients with some degree of immunosuppression-RANKL inhibitors did not significantly alter inflammatory processes. RANKL, RANK, and OPG deficiency in murine models highlights the important role of this pathway in the development and maturation of the immune system in rodents, including functions of T and/or B cells, whereas OPG overexpression in mice and rats seems innocuous with regard to immunity. In contrast, loss-of-function mutations in humans have more limited effects on immune cells. In clinical studies, the overall rate of infections, cancer, and death was similar with denosumab and placebo. Nevertheless, the risk of severe infections and cancer in some specific tissues remains to be carefully scrutinized. PMID- 20571773 TI - Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. AB - Vertebral Fracture Analysis enables the detection of vertebral fractures in the same session as bone mineral density testing. Using this method in 2,424 patients, we found unknown vertebral fractures in approximately one out of each six patients with significant impact on management. INTRODUCTION: The presence of osteoporotic vertebral fractures (VF) is an important risk factor for all future fractures independent of BMD. Yet, determination of the VF status has not become standard practice. Vertebral Fracture Assessment (VFA) is a new feature available on modern densitometers. In this study we aimed to determine the prevalence of VF using VFA in all patients referred for BMD testing in a university medical center and to evaluate its added clinical value. METHODS: Prospective diagnostic evaluation study in 2,500 consecutive patients referred for BMD. Patients underwent VFA in supine position after BMD testing. Questionnaires were used to assess perceived added value of VFA. RESULTS: In 2,424 patients (1,573 women), results were evaluable. In 541 patients (22%), VFA detected a prevalent VF that was unknown in 69%. In women, the prevalence was 20% versus 27% found in men (p < 0.0001). The prevalence of VF was 14% in patients with normal BMD (97/678), increased to 21% (229/1,100) in osteopenia and to 26% in those with osteoporosis (215/646) by WHO criteria. After excluding mild fractures VF prevalence was 13% (322/2,424). In 468 of 942 questionnaires (50% response rate), 27% of the referring physicians reported VFA results to impact on patient management. CONCLUSIONS: VFA is a patient friendly new tool with a high diagnostic yield, as it detected unknown VF in one out of each six patients, with significant impact on management. We believe these findings justify considering VFA in all new patients referred for osteoporosis assessment in similar populations. PMID- 20571775 TI - Amounts and proportion of administered pyrene dose excreted as urinary 1 hydroxypyrene after dietary exposure to polycyclic aromatic hydrocarbons. AB - Although urinary 1-hydroxypyrene (1-OHP) is the most relevant parameter for assessing exposure to polycyclic aromatic hydrocarbons, the inability to further elucidate the intra- and inter-individual variability, specificity and kinetics makes it difficult to enhance its value as an exposure predictor. Therefore, this human control study examined the excretion kinetics of urinary 1-OHP after consuming barbecued meat. Two feeding experiments were conducted, with doses of 15 and 30 g of barbecued meat per kg of body weight for experiments 1 and 2, respectively. All voided urine was collected for 7 days and analyzed for 1-OHP. In both experiments, the amounts of urinary 1-OHP excreted was significantly increased (P < 0.05) at 12 h post exposure but not at 12-24 h post exposure. Mean percentages of administered pyrene doses excreted as urinary 1-OHP at 0-12 h and 12-24 h post exposure were 3.80 and 0.61% in experiment 1 and 1.66 and 0.38% in experiment 2. Excretion ratio was inversely related to dose. A pattern of diurnal fluctuation (P < 0.05) in 1-OHP excretions was also identified. That is, 1-OHP excretions were smaller in the first half of the day (~0:00-12:00) than in the last half of the day (~12:00-24:00). This study demonstrated that, even at large dietary doses, most of the total urinary excretion of 1-OHP occurs within 12 h. Thus, subjects of occupational or environmental studies need only recall their diets for the current or previous day to diminish the influence from dietary pyrene. PMID- 20571774 TI - Effects of COLIA1 polymorphisms and haplotypes on perimenopausal bone mass, postmenopausal bone loss and fracture risk. AB - One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped for the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gen. We found that the -1997T allele and a haplotype containing it were associated with reduced bone mineral density (BMD) and increased bone turnover at menopause and after 10 years of follow-up. INTRODUCTION: We wanted to investigate whether the -1997G/T, -1663indelT and +1245G/T polymorphisms in the COLIA1 gene are associated with perimenopausal bone mass, early postmenopausal bone loss and interact with hormone treatment. METHODS: One thousand seven hundred seventeen perimenopausal women from the Danish Osteoporosis Prevention Study were genotyped, and haplotypes were determined. BMD was examined by dual X-ray absorptiometry. RESULTS: Women carrying the -1997T variant had lower BMD at all measured sites: lumbar spine BMD 1.030 +/- 0.137 g/cm(2), 1.016 +/- 0.147 g/cm(2) and 0.988 +/- 0.124 g/cm(2) in women with the GG, GT and TT genotypes, respectively (p < 0.05) and total hip BMD 0.921 +/- 0.116 g/cm(2), 0.904 +/- 0.123 g/cm(2) and 0.887 +/- 0.109 g/cm(2) in women with the GG, GT and TT genotypes, respectively (p = 0.01). The effect remained after 10 years although statistical significance was lost. Haplotype 3 ( 1997T-1663ins + 1245G) was associated with lower bone mass and higher levels of bone turnover. Compared with haplotype 1, haplotype 3 carriers had lower BMD at the lumbar spine, femoral neck and total hip by 0.016 +/- 0.007 g/cm(2), 0.015 +/ 0.006 g/cm(2) and 0.017 +/- 0.006 g/cm(2), respectively (p < 0.05-0.005). No association with postmenopausal changes in bone mass and fracture risk and no overall interaction with the effects of hormone therapy could be demonstrated for any of the polymorphisms in COLIA1. CONCLUSIONS: The -1997G/T polymorphism and haplotype 3 are significantly associated with perimenopausal bone mass, and these effects were sustained up to 10 years after menopause. No association between the -1663indelT or +1245G/T polymorphisms and peri- or postmenopausal bone mass could be demonstrated. PMID- 20571776 TI - Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch. AB - Ketoprofen (KP) is a widely used transdermal non-steroidal anti-inflammatory drug. However, increasing number of adverse effect case reports suggests that KP transdermal formulation can cause photoallergic reaction. The photoallergic potential of KP is attributable to the instability of KP under UV/visible light and subsequent formation of reactive degradation products. In this study, we investigated whether the inclusion of titanium dioxide (TiO(2)), a well-known mineral sunscreen agent, in the KP transdermal patch can prevent the photodegradation of KP and ultimately, can reduce photoallergic reaction. TiO(2) inclusion in fabric backing effectively decreased the UV transmission through fabric patch throughout all UVA region from 320 to 380 nm and consistently, KP patch with TiO(2) exhibited significantly increased photostability of KP. This enhanced photostability of KP resulted in reduced generation of photodegradation product as determined by HPLC-UV analysis. In a good accordance with these in vitro results, photosensitization test in guinea pig in vivo demonstrated low photoallergic reactions of KP patch with TiO(2) compared to KP patch without TiO(2), indeed. This study demonstrated that KP transdermal patch with TiO(2) included backing can provide with improved photostability and photosafety over conventional fabric KP patch. PMID- 20571777 TI - Genetic variants associated with arsenic metabolism within human arsenic (+3 oxidation state) methyltransferase show wide variation across multiple populations. AB - Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. The objective of this study was to investigate the diversity of the AS3MT gene in Mexican and German populations. The distribution of 18 single nucleotide polymorphisms (SNPs) in AS3MT was assessed on healthy individuals: 38 Mestizo, 69 Nahuas, 50 Huicholes, and 32 Germans. All 18 SNPs were polymorphic in the German and Mexican populations. Of the three Mexican populations, a minor allele frequency was the highest in the Mestizo, followed by the Nahuas and Huicholes. In the German and three Mexican groups, haplotype #1(TATAGAAGTCTTCATGAC) was the most predominant. Seven haplotypes were newly found in the German and three Mexican populations. The D' values between SNP pairs were high in the German and Nahua populations; they had a similar pattern. The pattern of the Mestizo was more similar to the African than to the other Mexican populations. Huicholes had a moderate pattern of the African and German/Nahua populations. The network had three clusters. One originated in the African population and another may have originated in an Asian (Chinese and/or Japanese) population. The third one may have originated among Caucasians. This study is the first to demonstrate the existence of genetic heterogeneity in the distribution of 18 SNPs in AS3MT of German and Mexican populations. PMID- 20571778 TI - Evaluation of the cytotoxic and antimutagenic effects of biflorin, an antitumor 1,4 o-naphthoquinone isolated from Capraria biflora L. AB - Biflorin is a natural quinone isolated from Capraria biflora L. Previous studies demonstrated that biflorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration dependent cytotoxic, genotoxic, antimutagenic, and protective effects of biflorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using different approaches. In the Salmonella/microsome assay, biflorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biflorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biflorin did not induce significant mutagenic and recombinogenic effects at the employed concentration range. In addition, the pre-treatment with biflorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H(2)O(2)) in S. cerevisiae. In V79 mammalian cells, biflorin was cytotoxic at higher concentrations. Moreover, at low concentrations biflorin pre-treatment protected against H(2)O(2) induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modified comet assay using DNA glycosylases. Our results suggest that biflorin cellular effects are concentration dependent. At lower concentrations, biflorin has significant antioxidant and protective effects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H(2)O(2) in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biflorin is cytotoxic and genotoxic. PMID- 20571779 TI - EP4 upregulation of Ras signaling and feedback regulation of Ras in human colon tissues and cancer cells. AB - Previous studies indicate that COX-2 and prostaglandin E(2) (PGE(2)) receptor subtypes are involved in intestinal carcinogenesis and activation of downstream pathways. In this report, we try to understand the association of PGE(2) receptor and K-ras cellular mechanism during the development of colorectal cancer. We collected 21 colorectal cancer patients and compared the protein expression of tumor tissues and normal mucosa tissues by using immunoblot. Furthermore, we transferred empty vector and pcDNA-K-ras into Ras-HT29 colon cancer cells. Result showed that phosphorylation of Akt and EP(1)/EP(4) were over-expressed in the colorectal tumor tissue. K-ras induces HT29 cells proliferation through the expressions of COX-2, EP1/EP4, pAkt, GSK3beta and increases Tcf transcriptional factor activation. Additionally, Ras protein was suppressed when treated with EP(4) inhibitor in Ras-HT29 cell. In cell cycle assay, K-ras mutation causing cell cycle S phase was prolonged with an increase in the G2/M phase ratio. In conclusion, we suggested that Ras overexpression leads to cell proliferation through activating Ras/PI3K/GSK3beta/EP(4) PGE(2) receptor signals and caused a feedback regulation of Ras by EP4 in colorectal tumor progression. PMID- 20571780 TI - Dose-dependent differences in short ultrasonic vocalizations emitted by rats during cocaine self-administration. AB - RATIONALE: The motivational impetuses underlying self-administration of cocaine and other drugs of abuse are not fully understood. One emerging factor is affect. Both positive and negative affective states have been hypothesized to influence drug seeking and drug taking. In parallel, it has been posited that the ultrasonic vocalizations (USVs) of Rattus norvegicus provide insight into the animals' affective reactions. Furthermore, it has been shown that mesolimbic dopamine (DA) plays a key role in cocaine self-administration and in USV production. Thus, affective processing as measured by rodent USVs likely coincides with cocaine self-administration, but to date has not been studied. OBJECTIVE: The present study examined USVs in both the negative affective (18 32.99 kHz) and positive affective (38-80 kHz) ranges of rats during self administration of a low (0.355 mg/kg/infusion) or high (0.71 mg/kg/infusion) dose of cocaine. RESULTS: USVs in both ranges were observed in both dose groups. Vocalizations of the low-dose animals occurred primarily in the 22-kHz range (18 32.99 kHz), but exhibited shorter durations (10-500 ms) than those traditionally observed for 22-kHz calls in aversive situations. In contrast, USVs of the high dose group were primarily observed in the 50-kHz frequency range (38-80 kHz), typically associated with appetitive outcomes. CONCLUSIONS: These results provide evidence for the presence of USVs during cocaine self-administration. The observed dose-dependent difference in USVs provides novel support for the view that affect is one potential motivational factor influencing human drug use and relapse behaviors. Rodent USVs may provide a powerful tool for understanding the role of affect in addiction. PMID- 20571781 TI - A follow-up study: acute behavioural effects of Delta(9)-THC in female heterozygous neuregulin 1 transmembrane domain mutant mice. AB - RATIONALE: Heavy cannabis use is linked with an increased risk for schizophrenia. We showed previously that male heterozygous neuregulin 1 transmembrane domain (Nrg1 HET) mice are more sensitive to some effects of the psychotropic cannabis constituent Delta(9)-tetrahydrocannabinol (THC). We report data from a follow-up study in female Nrg1 HET mice, investigating THC effects on behaviours with some relevance to schizophrenia. METHODS: Mice were injected with THC (0, 5 or 10 mg/kg i.p.) 30 min before a test battery: open field, elevated plus maze, novel object recognition (set 1) or light-dark, social interaction (SI) and prepulse inhibition (PPI 1: variable interstimulus interval (ISI); set 2). Another set (set 3) was injected with the same doses of THC before a fixed interstimulus interval PPI test (PPI 2). RESULTS: Female Nrg1 HETs displayed the hallmark increased locomotor activity at 5 months and anxiolytic-like behaviour in the open field at 3 and 5 months. THC decreased locomotor activity in both genotypes. THC selectively reduced some SI behaviours in WT mice. Baseline PPI was enhanced in mutants under a variable ISI, while THC had no effect on PPI using either protocol. CONCLUSIONS: This study reports novel findings on the baseline PPI profile and resistance to THC-induced social withdrawal in female Nrg1 HET mice. This is the first description of THC effects in females of this mouse model and suggests that the transmembrane domain Nrg1 mutation does not appear to have a severe impact on the behavioural sensitivity to THC in female mice. PMID- 20571782 TI - Laboratory assessment by combined z score values in proficiency tests: experience gained through the European Union proficiency tests for pesticide residues in fruits and vegetables. AB - The obligation for accredited laboratories to participate in proficiency tests under ISO 17025, performing multiresidue methods (MRMs) for pesticide residues, involves the reporting of a large number of individual z scores making the evaluation of the overall performance of the laboratories difficult. It entails, time and again, the need for ways to summarise the laboratory's overall assessment into a unique combined index. In addition, the need for ways to continually evaluate the performance of the laboratory over the years is equally acknowledged. For these reasons, following 14 years of the European Union Reference Laboratory for Pesticide Residues in Fruits and Vegetables (EUPT-FV), useful formulas have been designed to globally evaluate the assessment of the participating laboratories. The aim is to achieve a formula which is easy to understand, which can be applied and which fits the purposes of long-term evaluation detecting positive and negative trends. Moreover, consideration is needed for a fair compensation of bad results in MRM, taking into account the large number of compounds that are covered. It is therefore important to be aware of the difficulties in getting satisfactory values from a wide range of compounds. This work presents an evaluation of the main well-established combined z score formulas together with those new ones developed here which have been applied to the European proficiency test results (EUPTs) over the years. Previous formulas such as the rescaled sum of z score (RSZ), the sum squared of z score (SSZ) and the relative laboratory performance (RLP) are compared with the newer ones: the sum of weighted z scores (SWZ) and the sum of squared z scores (SZ2). By means of formula comparisons, conclusions on the advantages, drawbacks and the most fit-for-purpose approach are achieved. PMID- 20571783 TI - Spatial maps for time and motion. AB - In this article, we review recent research studying the mechanisms for transforming coordinate systems to encode space, time and motion. A range of studies using functional imaging and psychophysical techniques reveals mechanisms in the human brain for encoding information in external rather than retinal coordinates. This reinforces the idea of a tight relationship between space and time, in the parietal cortex of primates. PMID- 20571784 TI - Top-down and bottom-up attentional guidance: investigating the role of the dorsal and ventral parietal cortices. AB - Recent neuroimaging studies suggest that the superior parietal lobule (SPL) of the human cortex mediates goal-directed attentional orienting, while the temporo parietal junction (TPJ) mediates stimulus-driven attentional orienting. Here, we investigated these brain-behavior correspondences by examining the performance of patients with an attentional deficit following a right hemisphere lesion. Patients completed two tasks, one sensitive to stimulus-driven attentional orienting and the other to goal-directed attentional orienting. Based on the behavioral profiles obtained on each task, patients were assigned to different groups and their lesion overlap explored. Patients who exhibited difficulties with goal-directed attentional orienting and showed concurrent "hyper-capture" presented with lesion overlap centered over superior portions of the parietal lobule with spared inferior portions of the parietal lobule. Patients who performed normally on the goal-directed orienting task, while remaining abnormally immune to attentional capture, presented with lesion overlap centered over the inferior portions of the parietal lobule but spared superior parietal lobule. The findings from this study clearly suggest that (a) SPL and TPJ are anatomical regions that are recruited for the purposes of top-down and bottom-up orienting, respectively, and that damage to SPL and TPJ leads to disorders of top down and bottom-up orienting, and (b) albeit dissociable, top-down and bottom-up orienting (and, by extension, SPL and TPJ) are not entirely independent mechanisms. PMID- 20571785 TI - Functional MRI mapping neuronal inhibition and excitation at columnar level in human visual cortex. AB - The capability of non-invasively mapping neuronal excitation and inhibition at the columnar level in human is vital in revealing fundamental mechanisms of brain functions. Here, we show that it is feasible to simultaneously map inhibited and excited ocular dominance columns (ODCs) in human primary visual cortex by combining high-resolution fMRI with the mechanism of binocular inhibitory interaction induced by paired monocular stimuli separated by a desired time delay. This method is based on spatial differentiation of fMRI signal responses between inhibited and excited ODCs that can be controlled by paired monocular stimuli. The feasibility and reproducibility for mapping both inhibited and excited ODCs have been examined. The results conclude that fMRI is capable of non invasively mapping both excitatory and inhibitory neuronal processing at the columnar level in the human brain. This capability should be essential in studying the neural circuitry and brain function at the level of elementary cortical processing unit. PMID- 20571786 TI - Changes in cross-sectional area of spinal canal and vertebral body under 2 years of teriparatide treatment: results from the EUROFORS study. AB - The treatment of osteoporotic patients with teriparatide is associated with a significant increase in bone formation and gain of bone mass. The purpose of this post hoc analysis was to determine if the cross-sectional area (CSA) of the spinal canal and the vertebral body is affected by teriparatide treatment. Narrowing of the spinal canal might represent a safety problem, while widening of the vertebral CSA might improve mechanical stability. High-resolution computed tomography (HRCT) scans of vertebra T12 were obtained at baseline and after 6, 12, and 24 months of teriparatide treatment (20 microg/day) from 44 postmenopausal women with established osteoporosis participating in the prospective, randomized EUROFORS study. The CSA of the spinal canal did not decrease but increased marginally by 0.9% (2.6 mm(2)) over 24 months (P < 0.001), with a range from -0.5% (-2 mm(2)) to 3.1% (+8 mm(2)). Even when analyzing the spinal CSA on a slice-by-slice basis, no clinically relevant narrowing of the spinal canal was observed. For vertebral bodies, the CSA increased by 0.7% (5.7 mm(2)) over 24 months (P < 0.001), with a range from -0.4% (-3 mm(2)) to 1.6% (+14 mm(2)). Our data do not provide evidence for safety concerns regarding spinal canal narrowing. On the other hand, the increases observed for vertebral CSA apparently also only minimally contribute to the mechanical strengthening of the vertebral body under teriparatide treatment. PMID- 20571787 TI - Distinction between postoperative recurrent glioma and radiation injury using MR diffusion tensor imaging. AB - INTRODUCTION: This study aims to evaluate the differentiated effectiveness of MR diffusion tensor imaging (DTI) to postoperative recurrent glioma and radiation injury. METHODS: Conventional MRI and DTI examination were performed using Siemens 3.0 T MR System for patients with new contrast-enhancing lesions at the site of treated tumor with postoperative radiotherapy. The region of interest was manually drawn on ADC and FA maps at contrast-enhancing lesion area, peri-lesion edema, and the contra-lateral normal white matter. Then ADC and FA values were measured and, the ADC ratio and FA ratio were calculated. Twenty patients with recurrent tumor and 15 with radiation injury were confirmed by histopathologic examination (23 patients) and clinical imaging follow-up (12 patients), respectively. The mean ADC ratio and FA ratio were compared between the two lesion types. RESULTS: The mean ADC ratio at contrast-enhancing lesion area was significantly lower in patients with recurrent tumor (1.34 +/- 0.15) compared to that with radiation injury (1.62 +/- 0.17; P < 0.01). The mean FA ratio at contrast-enhancing lesion area was significantly higher in patients with recurrent tumor (0.45 +/- 0.03) compared to that with radiation injury (0.32 +/- 0.03; P < 0.01). Neither mean ADC ratio nor FA ratio in edema areas had statistical difference between the two groups. A recurrent tumor was suggested when either ADC ratio <1.65 or/and FA ratio >0.36 at contrast-enhancing lesion area according to the receiver operating characteristics curve analysis. Three patients with recurrent tumor and two with radiation injury were misclassified. CONCLUSION: DTI is a valuable method to distinguish postoperative recurrent glioma and radiation injury. PMID- 20571788 TI - Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety. AB - INTRODUCTION: Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. METHODS: Of 162 patients participating in a long term (>4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. RESULTS: Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38< >56%) at baseline and 42 of 100 patients (42%; 95%CI32<->52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9<->67%) and 27% (95%CI4<->50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. CONCLUSIONS: Patients with coiled intracranial aneurysms participating in long term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months. PMID- 20571789 TI - Trichuriasis colitis detected by Doppler sonography. AB - Trichuriasis affects children at an estimated prevalence rate of 17% in the world population. It sometimes affects the colon and causes unspecific symptoms and laboratory findings. This case describes a child with unspecific abdominal symptoms. Color Doppler sonography showed signs of diffuse colitis and colonoscopy demonstrated colonic infection by Trichuris. US was useful to orient the investigation. We describe color Doppler sonography findings and review the medical literature about the radiological findings of this entity. PMID- 20571790 TI - Parotid metastasis from adrenal neuroblastoma. AB - Neuroblastomas are the most common extracranial solid malignancy in children. In contrast, salivary gland tumors are uncommon in children, accounting for only 1% of all pediatric neoplasms. Parotid metastases are rare; only two cases of parotid metastases from neuroblastomas have been reported with an emphasis on the pathology. We present a case of a parotid metastasis from a neuroblastoma with in depth description and discussion of its ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) appearances. PMID- 20571791 TI - Developmental changes of radiological findings in Fukuyama-type congenital muscular dystrophy. AB - Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital muscular dystrophy and associated with neuropathological anomalies. However, the issue of whether the radiological findings of white-matter lesions represent delayed myelination, demyelination or other problems remains controversial. We present serial radiological findings, including MR spectroscopy (MRS), in a child with FCMD. These findings indicate a correlation between the imaging abnormalities and the choline/creatine ratio, suggesting the possible usefulness of MRS in addition to MRI for following FCMD patients. PMID- 20571792 TI - Mosquito-bacteria symbiosis: the case of Anopheles gambiae and Asaia. AB - The symbiotic relationship between Asaia, an alpha-proteobacterium belonging to the family Acetobacteriaceae, and mosquitoes has been studied mainly in the Asian malaria vector Anopheles stephensi. Thus, we have investigated the nature of the association between Asaia and the major Afro-tropical malaria vector Anopheles gambiae. We have isolated Asaia from different wild and laboratory reared colonies of A. gambiae, and it was detected by PCR in all the developmental stages of the mosquito and in all the specimens analyzed. Additionally, we have shown that it localizes in the midgut, salivary glands and reproductive organs. Using recombinant strains of Asaia expressing fluorescent proteins, we have demonstrated the ability of the bacterium to colonize A. gambiae mosquitoes with a pattern similar to that described for A. stephensi. Finally, fluorescent in situ hybridization on the reproductive tract of females of A. gambiae showed a concentration of Asaia at the very periphery of the eggs, suggesting that transmission of Asaia from mother to offspring is likely mediated by a mechanism of egg-smearing. We suggest that Asaia has potential for use in the paratransgenic control of malaria transmitted by A. gambiae. PMID- 20571793 TI - Oxidation of elemental sulfur by Fusarium solani strain THIF01 harboring endobacterium Bradyrhizobium sp. AB - Nineteen fungal strains having an ability to oxidize elemental sulfur in mineral salts medium were isolated from deteriorated sandstones of Angkor monuments. These fungi formed clearing zone on agar medium supplemented with powder sulfur due to the dissolution of sulfur. Representative of the isolates, strain THIF01, was identified as Fusarium solani on the basis of morphological characteristics and phylogenetic analyses. PCR amplification targeting 16S rRNA gene and analyses of full 16S rRNA gene sequence indicated strain THIF01 harbors an endobacterium Bradyrhizobium sp.; however, involvement of the bacterium in the sulfur oxidation is still unclear. Strain THIF01 oxidized elemental sulfur to thiosulfate and then sulfate. Germination of the spores of strain THIF01 was observed in a liquid medium containing mineral salts supplemented with elemental sulfur (rate of germinated spores against total spores was 60.2%), and the culture pH decreased from pH 4.8 to 4.0. On the contrary, neither germination (rate of germinated spores against total spores was 1.0%) nor pH decrease was observed without the supplement of elemental sulfur. Strain THIF01 could also degrade 30 ppmv and ambient level (approximate 500 pptv) of carbonyl sulfide. PMID- 20571794 TI - Impact of linoleic acid supplementation on lovastatin production in Aspergillus terreus cultures. AB - This work proposes a novel approach for enhancing the yield of lovastatin in Aspergillus terreus cultures by exploiting linoleic acid-derived signalling molecules, which are potentially involved in fungal cell-cell communication. High performance liquid chromatography analysis revealed that production of lovastatin was enhanced up to 1.8-fold upon exogenous addition of the oxylipin precursor linoleic acid to low cell density cultures of A. terreus. Real-time PCR analysis showed that supplementation of linoleic acid also resulted in an increase in transcriptional levels of lovastatin biosynthetic genes lovB and lovF, indicating a transcriptional control of fatty acids (linoleic acid) on these genes in A. terreus. This study therefore demonstrates for the first time the potential of an oxylipin molecule as an enhancer of a fungal secondary metabolite production with positive impact for industrial exploitation. PMID- 20571795 TI - Broad-host-range plasmid-mediated metabolic perturbations in Pseudomonas fluorescens 13525. AB - Genetic engineering of fluorescent pseudomonads for various industrially, agriculturally and environmentally important bioprocesses often involves the use of suitable plasmids. Plasmid-mediated alterations in host physiology and metabolism are poorly understood for this group of organisms. Thus, we investigated the metabolic perturbations in Pseudomonas fluorescens 13525 due to the independent and combined presence of broad-host-range plasmids, pBBR1MCS-2 (copy number 30) and pUCPM18 derived pAB4 and pAB8 (copy number 14-16). Presence of pAB4 and pAB8 not only significantly increased the growth rate and glucose utilization of P. fluorescens 13525, but also increased glucose dehydrogenase activity and gluconic acid production indicating enhanced direct oxidative pathway for glucose catabolism. Additionally, increased secretion of pyruvic, acetic, and citric acids caused faster media acidification in presence of pAB4 and pAB8. Simultaneous presence of pAB4/pAB8 in Pf (pAB48) and pAB4/pBBR1MCS-2 in Pf (pAB4BBR1MCS-2) reduced their respective copy numbers to nearly half. Pf (pAB48) demonstrated further increase in direct oxidation pathway without altering growth and glucose depletion rates, as compared with single transformants. Conversely, pBBR1MCS-2 plasmid did not greatly alter P. fluorescens 13525 metabolism when present independently but masked the effects imposed by pAB4 when present in its combination. In conclusion, P. fluorescens 13525 redesigns its metabolism in response to the presence of plasmids irrespective of their nature, by enhancing anaplerosis with a simultaneous reduction in catabolism as indicated by increased pyruvate carboxylase and decreased citrate synthase activities, respectively. Such information will be helpful for vector designing during genetic engineering of fluorescent pseudomonads. PMID- 20571797 TI - Spatio-temporal variability of soil respiration of forest ecosystems in China: influencing factors and evaluation model. AB - Understanding the influencing factors of the spatio-temporal variability of soil respiration (R (s)) across different ecosystems as well as the evaluation model of R (s) is critical to the accurate prediction of future changes in carbon exchange between ecosystems and the atmosphere. R (s) data from 50 different forest ecosystems in China were summarized and the influences of environmental variables on the spatio-temporal variability of R (s) were analyzed. The results showed that both the mean annual air temperature and precipitation were weakly correlated with annual R (s), but strongly with soil carbon turnover rate. R (s) at a reference temperature of 0 degrees C was only significantly and positively correlated with soil organic carbon (SOC) density at a depth of 20 cm. We tested a global-scale R (s) model which predicted monthly mean R (s) (R (s,monthly)) from air temperature and precipitation. Both the original model and the reparameterized model poorly explained the monthly variability of R (s) and failed to capture the inter-site variability of R (s). However, the residual of R (s,monthly) was strongly correlated with SOC density. Thus, a modified empirical model (TPS model) was proposed, which included SOC density as an additional predictor of R (s). The TPS model explained monthly and inter-site variability of R (s) for 56% and 25%, respectively. Moreover, the simulated annual R (s) of TPS model was significantly correlated with the measured value. The TPS model driven by three variables easy to be obtained provides a new tool for R (s) prediction, although a site-specific calibration is needed for using at a different region. PMID- 20571796 TI - Bony sequestrum: a radiologic review. AB - According to a pathological definition, a bony sequestrum is defined as a piece of devitalized bone that has been separated from the surrounding bone during the process of necrosis. However, the radiological definition of a sequestrum is different and refers to an image of calcification visible within a lucent lesion, completely separated from the surrounding bone, without referring to the vascular status and histological nature of the calcified tissue. The term "button sequestrum" has been used in calvarial lesions. The prototype conditions that may present with a bony sequestrum are osteomyelitis and skeletal tuberculosis. Other conditions such as radiation necrosis, eosinophilic granuloma, metastatic carcinoma, primary lymphoma of bone, aggressive fibrous tumors may also manifest as osteolytic lesions containing a sequestrum. In addition, some primary bone tumors produce a matrix that may mineralize and sometimes simulate a bone sequestrum. These include osteoid tumors (osteoid osteoma, osteoblastoma), cartilaginous tumors (chondroma and chondroblastoma), lipomatous tumors (lipoma), and benign fibrous tumors (fibromyxoma, myxoma, and desmoplastic fibroma). Therefore, various conditions may present at imaging as a small area of osteolysis containing central calcifications. However, a careful analysis of the sequestrum as well as the associated clinical and radiological findings often enables to point toward a limited number of conditions. PMID- 20571798 TI - Backbone-free transformation of barrel medic (Medicago truncatula) with a Medicago-derived transfer DNA. AB - In the present work, Agrobacterium tumefaciens-mediated genetic transformation of the model legume Medicago truncatula Gaertn. (barrel medic) was carried out using the pSIM843 vector that contains a Medicago-derived transfer DNA, delineated by a 25-bp sequence homologous to bacterial T-DNA borders. The transfer DNA contains an expression cassette for the nptII (neomycin phosphotransferase) gene and is flanked by an expression cassette for the backbone integration marker gene ipt (isopentenyl transferase). Our results demonstrate that the Medicago-derived RB like elements efficiently support DNA mobilization from A. tumefaciens to M. truncatula. Kanamycin-resistant shoots with normal phenotype and ipt-shooty lines were recovered at a frequency of 11.7 and 7.8%, respectively. Polymerase chain reaction (PCR) analyses demonstrated that 44.4% of the independent transgenic lines were backbone-free and evidenced the occurrence of backbone-transfer events. PMID- 20571799 TI - Mammography and ultrasound in the evaluation of male breast disease. AB - OBJECTIVE: To assess clinical variables that may be useful in differentiating gynaecomastia from carcinoma and to analyse the contribution of mammography and ultrasound to the evaluation of male breast disease. METHODS: All men who underwent mammography and/or ultrasound between 1993 and 2006 in our hospital were retrospectively evaluated. Clinical characteristics in patients with gynaecomastia and those with carcinoma were compared. Radiological findings were classified according to the BI-RADS (Breast Imaging Reporting and Data System) criteria. The diagnostic performance of physical examination, mammography and ultrasound was determined and compared. RESULTS: A total of 628 patients with 518 mammograms and 423 ultrasounds were reviewed. The final diagnoses were: 19 carcinomas, 526 gynaecomastias, 84 other benign conditions and 25 normal. There were statistically significant differences in age, bilateral involvement, clinical presentation and physical examination between patients with carcinoma and those with gynaecomastia. The diagnostic performance of physical examination was lower than that of mammography and ultrasound (p < 0.05 for specificity). Mammography was the most sensitive (94.7%) and ultrasound the most specific (95.3%) for detection of malignancy (p > 0.05). We propose an algorithm for the use of mammography and ultrasound in men. CONCLUSIONS: Mammography and ultrasound, with a negative predictive value close to 100%, make it possible to avoid very many unnecessary surgical procedures in men. PMID- 20571800 TI - Pulmonary ventilation and perfusion imaging with dual-energy CT. AB - OBJECTIVE: To evaluate the feasibility of dual-energy CT (DECT) ventilation imaging in combination with DE perfusion mapping for a comprehensive assessment of ventilation, perfusion, morphology and structure of the pulmonary parenchyma. METHODS: Two dual-energy CT acquisitions for xenon-enhanced ventilation and iodine-enhanced perfusion mapping were performed in patients under artificial respiration. Parenchymal xenon and iodine distribution were mapped and correlated with structural or vascular abnormalities. RESULTS: In all datasets, image quality was sufficient for a comprehensive image reading of the pulmonary CTA images, lung window images and pulmonary functional parameter maps and led to expedient results in each patient. CONCLUSION: With dual-source CT systems, DECT of the lung with iodine or xenon administration is technically feasible and makes it possible to depict the regional iodine or xenon distribution representing the local perfusion and ventilation. PMID- 20571801 TI - Comparative efficiency of contrast-enhanced colour Doppler ultrasound targeted versus systematic biopsy for prostate cancer detection. AB - OBJECTIVE: To compare the efficiency of contrast-enhanced colour Doppler ultrasound (CECD-US) targeted biopsy versus systematic biopsy (SB) for PCa detection in 1,776 men. METHODS: Retrospective, single-centre, diagnostic accuracy study from 2002 until 2006 in 1,776 male volunteers with a serum total PSA of 1.25 ng/ml or greater. In each patient five CECD-US targeted biopsies were performed in hypervascular areas in the peripheral zone during intravenous injection of a second-generation microbubble US contrast agent. Subsequently, another examiner performed ten SBs. The PCa detection rates for the two techniques were compared. RESULTS: Of 1,776 patients, cancer was detected in 559 patients (31%), including 476 of the 1,776 patients (27%) with CECD-US and 410 (23%) with SB (p < 0.001). The detection rate for CECD-US targeted biopsy cores (10.8% or 961 of 8,880 cores) was significantly better than for SB cores (5.1% or 910 of 17,760 cores, p < 0.001). Among patients with a positive biopsy for PCa, cancer was detected by CECD-US alone in 149 patients (27%) and by SB alone in 83 (15%) (p < 0.001). CONCLUSION: This study represents the largest clinical trial to date, demonstrating a significant benefit of CECD-US targeted biopsy relative to SB. PMID- 20571802 TI - Inverse mismatch and lesion growth in small subcortical ischaemic stroke. AB - OBJECTIVE: Infarction typically develops within the borders of an initial hypoperfused tissue. We prospectively investigated whether in small subcortical stroke patients infarct growth can occur beyond the margins of the affected vascular territories. METHODS: In 19 consecutive patients, stroke MRI was performed within 14 h after ictus, and at days 2 and 6 (+/- 1). Size of diffusion and perfusion disturbances were determined. Infarct volume measured on T2 weighted images on day 6 was considered as imaging endpoint. RESULTS: At the initial examination, the mean diffusion lesion [apparent diffusion coefficient (ADC) lesion size, 1.82 +/- 1.2 ml] was larger (p = 0.0002) than the perfusion lesion [mean transit time (MTT) lesion size, 0.72 +/- 0.69 ml]. Such an "inverse mismatch" (ADC lesion > MTT lesion) was present in 14/19 patients at baseline and in all patients on day 2. Final lesion volume at day 6 was 3.2 +/- 1.6 ml which was larger than the initial perfusion deficit (p = 0.02). CONCLUSION: In small subcortical ischaemic stroke "inverse mismatch" is frequent and infarction develops beyond the initial perfusion disturbance. This indicates that cytotoxic processes probably triggered by the infarct core are a dominant mechanism for lesion growth. Areas with normal perfusion but which are threatened by cytotoxic damage developing over several days seem prime targets for neuroprotective therapy. PMID- 20571803 TI - Analysis of intrahepatic vascular morphological changes of chronic liver disease for assessment of liver fibrosis stages by micro-flow imaging with contrast enhanced ultrasound: preliminary experience. AB - OBJECTIVE: To assess morphological vascular changes due to an increase in liver fibrosis by using micro-flow imaging (MFI) of contrast-enhanced ultrasound. METHODS: MFI was performed in 47 patients who underwent liver biopsy, and in 10 normal cases. For 27/57 cases, we performed MFI twice in order to assess the reproducibility of the examination, thus yielding a total of 84 examinations. Seven physicians interpreted each case individually by assigning confidence levels for the presence or absence of three imaging features that were related to alteration of portal vein morphology: angle widening, tapering/interruption and tortuosity. RESULTS: Pearson's correlation coefficient between the average rating scores based on tortuosity and the histological fibrosis stage was 0.806 (p < 0.001). The diagnostic accuracy of the average area under the ROC curve, which was estimated by use of the confidence levels of tapering/interruption, tortuosity and angle widening, was 0.964 for F1 vs. F2-4, 0.968 for F1-2 vs. F3-4 and 0.910 for F1-3 vs. F4. The average correlation coefficient between the ratings on different images from the same patients was 0.838. CONCLUSION: Assessment of morphological intrahepatic vascular changes on MFI may be useful for grading liver fibrosis. PMID- 20571804 TI - Comparison of standard- and low-tube voltage MDCT angiography in patients with peripheral arterial disease. AB - OBJECTIVE: We investigated the effect of low-tube-voltage CT angiography with a reduced volume of contrast agent on qualitative and quantitative parameters and the radiation dose in patients with peripheral arterial disease. METHODS: Eighty consecutive patients were divided into two groups; the protocol was 120 kVp and 1.8 ml/kg contrast agent (300 mgI/ml) in one group and 80 kVp and 1.2 ml/kg in the other. For quantitative analysis we calculated the mean arterial attenuation, the mean difference between maximum and minimum attenuation values, contrast-to noise ratio (CNR), and figure of merit (FOM). For qualitative evaluation, we used visual scores. RESULTS: There were no significant intergroup differences in mean arterial attenuation (120 vs. 80 kVp: 331.6 +/- 61.6 vs. 354.9 +/- 61.9 HU) and in the mean difference between maximum and minimum attenuation (120 vs. 80 kVp: 52.2 +/- 25.5 vs. 61.5 +/- 27.5 HU). While the mean CNR was significantly higher at 120 than 80 kVp (38.4 +/- 18.8 vs. 31.1 +/- 15.3), the mean FOM was not significantly different (120 vs. 80 kVp: 1.3 +/- 1.5 vs. 1.2 +/- 1.2), and there was no significant intergroup difference in visual scores. The mean dose-length product was significantly lower at 80 than 120 kVp (1,024.3 +/- 151.3 vs. 1,464.7 +/- 208.7 mGy.cm). CONCLUSION: The 80-kVp protocol allows for reduction of the radiation dose by approximately 30% and the volume of contrast agent by more than 30% without deterioration of vascular enhancement and image quality. PMID- 20571805 TI - [Retinal angiomatous proliferation with associated pigment epithelium detachment: anti-VEGF therapy]. AB - BACKGROUND: Vascularized pigment epithelial detachment (PED) in retinal angiomatous proliferation (RAP) represents a special morphological form of exudative age-related macular degeneration (ARMD) in the natural course and in the frequency of complications, such as tears in the pigment epithelium. In this study the results of inhibition of vascular endothelial growth factor (VEGF) for exudative ARMD with associated PED and RAP were examined. MATERIALS AND METHODS: Functional and morphological data were retrospectively collected for 61 consecutive eyes with RAP in stages 2 and 3 over an average observation period of 108 weeks. Patients were treated with bevacizumab (n=15), ranibizumab (n=29) and pegabtanib (n=17) according to the recommendations of the German Society of Ophthalmology (DOG) and the German Retina Society (RG). After an initial treatment cycle of 3 injections every 4 weeks (6 weeks for pegabtanib), best corrected visual acuity (BCVA), fluorescence angiography (FAG), indocyanine green angiography (ICG-A) and optical coherence tomography (OCT) were evaluated every 12 weeks. RESULTS: The mean visual acuity was 0.8 logMAR before therapy and 0.77 logMAR after therapy so that the average difference to the original acuity was 0.03 logMAR after 12 weeks and 0.00 logMAR after 48 weeks. The central retinal thickness measured by OCT decreased on average by 81.2 um after the first cycle of injections and by -68.4 um after 1 year. The maximum depth of PED could be reduced on average by 1 unit and after 1 year by 1.55 units. Better functional and morphological results were obtained by therapy with ranibizumab and avastin compared to pegabtanib (p=0.03). An RIP occurred in 9.8% of the patients (n=6) on average after 16 weeks. CONCLUSIONS: The morphological functional results can be improved in the early months using the therapy strategy presently recommended in Germany. However, in later stages there was a significant worsening of the functional results. Modification of the treatment strategy with respect to close surveillance and possibly early stage repeat treatment would seem advisable. PMID- 20571806 TI - [Systemic voclosporin for uveitis treatment]. AB - To date cyclosporine is the only immunosuppressive drug approved for the treatment of uveitis in Germany. However, side effects often limit its use in daily practice. Voclosporin (Luveniq) represents a next generation calcineurin inhibitor which had shown efficacy in an animal model of experimental autoimmune uveitis as well as in clinical trials for the prevention of renal allograft rejection and for plaque psoriasis. The LUMINATE program included three prospective, randomized, double-masked, placebo-controlled multicenter trials which demonstrated the efficacy and tolerability of voclosporin 0.4 mg/kg b.i.d. in noninfectious intermediate and posterior uveitis and panuveitis. In Europe, the Marketing Approval Application (MAA) of voclosporin for the treatment of uveitis was submitted to the European Medicines Agency (EMA) in February 2010 and could be approved in March 2011. PMID- 20571807 TI - [Infrared imaging of outer lamellar macular holes]. AB - BACKGROUND: Outer lamellar macular holes (OLMH) are very rare compared to inner lamellar macular holes. An OLMH can occur associated with optic pit maculopathy, in the progression of myopic macular retinoschisis, transient in the development of full thickness macular holes or idiopathic. This article reports on infrared imaging of OLMHs. METHODS: Infrared (IR) images in 2 patients aged 22 and 34 years with OLMH were taken using IR reflection at a wavelength of 820 nm with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2, Heidelberg Engineering). IR images were correlated with linear optical coherence tomography (OCT) scans (Stratus-OCT, Zeiss). Images were acquired during follow up of up to 30 months and if applicable preoperatively and postoperatively. RESULTS: Clear infrared signals were recorded especially in OLMH associated with optic pit maculopathy. Correlation with linear OCT scans showed the enhanced infrared signals to be restricted to the extent of the OLMH. The borders of the OLMH could be clearly delineated. Infrared imaging enables a top view of OLMH and therefore allows an excellent documentation of the course of OLMH. CONCLUSIONS: Infrared reflection is useful for two-dimensional imaging of OLMH. Infrared imaging can provide a supplement to slice imaging for OCT diagnostics and allows monitoring of OLMH over time. The postoperative sequence of OLMH closure in patients with optic pit maculopathy can be studied in more detail using infrared imaging. PMID- 20571808 TI - [Evaluation of the need for communication training of ophthalmologists for gaining telephone consent for cornea donation]. AB - INTRODUCTION: Because of the gap between the high need for cornea tissue for transplantation and the current lower numbers of donors, there is high pressure to succeed in telephone calls to relatives of deceased for obtaining consent. Besides the attempt to increase the rate of donors, these telephone calls should be gentle for relatives and not overstrain professionals. This study assesses the need and expectations of physicians towards communication training in preparation for their task. METHODS: In September-October 2009 a needs assessment for communication training among physicians who currently work or have worked for the eye bank took place. Personal data were recorded and their estimate of the perceived burden as well as needs and potential benefits from a specific communication training for obtaining consent for cornea donation by telephone were assessed using numeric rating scales between 1 (minimum) and 10 (maximum). Results were expressed as mean and range. RESULTS: The participants felt only moderately prepared for the task regarding information content, their emotions and personal convictions. They considered a specific training to be highly meaningful, necessary and helpful. Their highest burden during telephone calls previously experienced was documented as 8.4 and the average burden as 6.3. Accordingly, their willingness to continue working at an eye bank after their rotation was moderate. DISCUSSION: Physicians involved in obtaining consent for cornea donation by telephone feel highly stressed and only moderately prepared for fulfilling the task both for the information content and on the emotional level. Accordingly, specific communication training is perceived as highly meaningful, necessary and helpful. An educational program was developed to meet the needs and expectations of physicians. PMID- 20571809 TI - [Mobile intraocular pressure measurement. From palpation to initial clinical experience with the handheld dynamic contour tonometer]. AB - Goldmann applanation tonometry is still the gold standard of intraocular pressure measurement (IOP) and an essential part in the diagnosis of glaucoma. Applanation tonometry is usually performed on a sitting patient at the slit lamp. However, under certain circumstances it is necessary to measure the IOP outside the office setting. With handheld devices the measuring procedure is brought to bedside and surgery theatres, as well as to patients who are not able to sit behind the slit lamp. The dynamic contour tonometer (DCT) represents a new method of direct IOP measurement. Its physical principle is based on piezo-electronic contour matching tonometry and is claimed to be less dependent on biochemical properties of the cornea. Besides the IOP, the ocular pulse amplitude can also be measured. Until now, the DCT had been available as a slit lamp mounted device. In this report, we present a portable prototype of the device. In comparison with the Perkins tonometer and the TONO-PEN XL, the handheld DCT shows smaller intra- and inter examiner variability. Additionally, the device offers the unique possibility to display the ocular pulse amplitude while the patient is in a horizontal position. PMID- 20571810 TI - [Pterygium surgery. Complication following adjuvant radiotherapy]. AB - Scleromalacia is a rare but serious complication following excision of an atypical pterygium and postoperative radiation which needs immediate action and treatment. In this case report we describe a successful method for treating this condition with amniotic membrane transplantation. Despite severe blepharoconjunctivitis the patient is now free of recurrence of pterygium for 3 years supporting the use of amnion membranes for covering scleromalacia in inflammatory conditions. PMID- 20571811 TI - [Non-arteritic central retinal artery occlusion]. PMID- 20571812 TI - Acid-base regulation in the plainfin midshipman (Porichthys notatus): an aglomerular marine teleost. AB - The plainfin midshipman (Porichthys notatus) possesses an aglomerular kidney and like other marine teleosts, secretes base into the intestine to aid water absorption. Each of these features could potentially influence acid-base regulation during respiratory acidosis either by facilitating or constraining HCO(3)(-) accumulation, respectively. Thus, in the present study, we evaluated the capacity of P. notatus to regulate blood acid-base status during exposure to increasing levels of hypercapnia (nominally 1-5% CO(2)). Fish exhibited a well developed ability to increase plasma HCO(3)(-) levels with values of 39.8 +/- 2.8 mmol l(-1) being achieved at the most severe stage of hypercapnic exposure (arterial blood PCO(2) = 21.9 +/- 1.7 mmHg). Consequently, blood pH, while lowered by 0.15 units (pH = 7.63 +/- 0.06) during the final step of hypercapnia, was regulated far above values predicted by chemical buffering (predicted pH = 7.0). The accumulation of plasma HCO(3)(-) during hypercapnia was associated with marked increases in branchial net acid excretion (J (NET)H(+)) owing exclusively to increases in the titratable alkalinity component; total ammonia excretion was actually reduced during hypercapnia. The increase in J (NET)H(+) was accompanied by increases in branchial carbonic anhydrase (CA) enzymatic activity (2.8*) and CA protein levels (1.6*); branchial Na(+)/K(+)-ATPase activity was unaffected. Rectal fluids sampled from control fish contained on average HCO(3)(-) concentrations of 92.2 +/- 4.8 mmol l(-1). At the highest level of hypercapnia, rectal fluid HCO(3)(-) levels were increased significantly to 141.8 +/- 7.4 mmol l(-1) but returned to control levels during post-hypercapnia recovery (96.0 +/- 13.2 mmol l(-1)). Thus, the impressive accumulation of plasma HCO(3)(-) to compensate for hypercapnic acidosis occurred against a backdrop of increasing intestinal HCO(3)(-) excretion. Based on in vitro measurements of intestinal base secretion in Ussing chambers, it would appear that P. notatus did not respond by minimizing base loss during hypercapnia; the increases in base flux across the intestinal epithelium in response to alterations in serosal HCO(3)(-) concentration were similar in preparations obtained from control or hypercapnic fish. Fish returned to normocapnia developed profound metabolic alkalosis owing to unusually slow clearance of the accumulated plasma HCO(3)(-). The apparent inability of P. notatus to effectively excrete HCO(3)(-) following hypercapnia may reflect its aglomerular (i.e., non-filtering) kidney coupled with the normally low rates of urine production in marine teleosts. PMID- 20571814 TI - [Learning complex linguistic structures beyond the age of 60. A comparison of four age groups over the lifespan and an analysis of facilitating factors for learning]. AB - Are people beyond the age of 60 years able to learn complex linguistic structures as successfully as younger people, if their educational backgrounds are similar? Can facilitating factors for learning be identified? A sample of 321 well educated subjects aged between 15 and 79 years were given identical fictional texts containing systematic stylistic features, subdivided into three different conditions inducing explicit, implicit or incidental learning. The oldest group of 60-79 year olds showed no differences in learning results or in the ability to verbalize the stylistic features compared to the younger groups, neither in the overall results nor under the different learning conditions. For the additional analysis of factors facilitating learning, another 15, less well-educated elderly subjects were included in the study. Better learning results were influenced by higher scholastic and vocational qualifications and an age of under 70 years, and were correlated with more reading and out-of-home activities. PMID- 20571813 TI - The protective effect of oral colitis-derived proteins in a murine model of inflammatory bowel disease is associated with an increase in gammadelta T cells in large intestinal mucosa. AB - BACKGROUNDS AND AIMS: Oral tolerance has previously been shown effective in preventing several immune-mediated disorders in animal models. The aims of this study were to investigate the effect of oral colitis-extracted proteins (CEP) on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice and to explore the relative role of the intestinal mucosal gammadelta T cells. METHODS: The effect of five low oral doses of CEP on colitis was evaluated by clinical manifestation and histological lesions. Serum cytokines were measured by enzyme-linked immunosorbent assay. The percentages of the intestinal mucosal gammadelta T cells were evaluated by flow cytometry. RESULTS: CEP-fed colitis mice showed less severe symptoms and histological injury than bovine serum albumin (BSA)-fed control mice. Tolerized mice developed an increase in TGF-beta1 and no change in IFN-gamma serum levels. Increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in small intestinal mucosal lymphocytes and no quantitative change in large intestinal mucosal lymphocytes were demonstrated in colitis mice compared to untreated mice. The proportions of TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes from CEP-fed colitis mice were significantly higher compared to BSA fed controls. The disease activity index negatively correlated with the percentages of large intestinal mucosal gammadelta T cells. Furthermore, mucosal repair in repair-period mice was also accompanied by increases in TCRgammadelta(+) T cells and CD8alpha(+)TCRgammadelta(+) T cells in large intestinal mucosal lymphocytes. CONCLUSION: Improvement of DSS-induced colitis that resulted from oral administration of colitis-extracted proteins is associated with an increase in gammadelta T cells in large intestinal mucosa. PMID- 20571815 TI - Continence profiles. A way to enhance assessment of urinary continence in German nursing practice. AB - The German expert standard "Promotion of urinary continence in nursing" was developed and implemented to support nursing practice. The group of experts involved identified the assessment of (in)continence situations and the evaluation of outcomes as a central problem for successful continence care. They, therefore, developed an assessment instrument in the German language, namely six continence profiles, to help differentiate between continence and incontinence. It also takes into account the extent to which the relevant situation can be promoted or compensated by the application of measures, on the one hand, and independently or dependent on nursing staff assistance, on the other hand. The profiles were developed based on theories and implemented into practice as a model. The current paper describes the theoretical background and development process as well as early results from implementation and testing. However, a comprehensive scientific study must still be performed. PMID- 20571819 TI - Four-repeat tauopathy clinically presenting as posterior cortical atrophy: atypical corticobasal degeneration? AB - A man aged 55 with negative family history presented with progressive decline in spatial orientation and visual functions for 2 years. He showed impaired optic fixation, optic ataxia, agraphia, acalculia, ideomotor apraxia, disturbed right left differentiation but preserved color matching, memory and motor perception, gradually progressing to dementia, without extrapyramidal signs. Brain MRI and PET showed severe bilateral atrophy and hypometabolism in parieto-occipital areas with sparing of visual perception area and frontal lobes. Treatment with cholinesterase inhibitors had no effect. Death occurred 61/2 years after onset of symptoms from bronchopneumonia. Clinical diagnosis was posterior cortical atrophy (Benson's syndrome). Autopsy showed severe bilateral parietal cortical atrophy, less severe in other brain regions without subcortical lesions. Histology revealed severe diffuse tauopathy with neuronal loss, neurofibrillary tangles, neuropil threads, and tau deposits in astroglia and oligodendroglia in parietal, temporal, occipital cortex, less in frontal cortex and hippocampus, putamen, claustrum, thalamus and subthalamus. Severely involved white matter showed many tau-positive threads, comma-like inclusions in oligodendroglia (coiled bodies) and in astroglia. Mild neuronal loss in substantia nigra was associated with massive tau pathology, also involving several brainstem nuclei, cerebellum being preserved. There were neither astrocytic plaques nor any amyloid pathology. Neuronal and glial inclusions were generally 4R-tau-positive and 3R-tau-negative. No TDP-43 and alpha-synuclein inclusions were detected. Spinal cord was not available. No mutations were found in the MAPT gene. This is the first published case with the fully developed clinical and neuroimaging picture of posterior cortical atrophy, morphologically presenting as a distinct phenotype of 4R tauopathy that closely resembles (atypical) CBD. PMID- 20571820 TI - Effectiveness of short-term maintenance treatment with cabergoline in microadenoma-related and idiopathic hyperprolactinemia. AB - OBJECTIVE: This study aimed to determine the effectiveness of short-term maintenance treatment with cabergoline and to find out minimum effective dosage of cabergoline during maintenance treatment for patients with microadenoma related and idiopathic hyperprolactinemia. STUDY DESIGN: Cabergoline was administered orally at a dose of 0.5 mg twice per week to 164 de novo hyperprolactinemic patients until serum prolactin level normalized. After this initial treatment phase, patients started on maintenance phase for which they were previously randomized. No maintenance treatment (Group I, n = 36) or cabergoline 0.5 mg (Group II, n = 46), 0.25 mg (Group III, n = 39), 0.125 mg (Group IV, n = 43) was administered twice per week for 8 weeks as maintenance treatment. Then, maintenance phase was finalized and patients were followed up for 6 months. Mean serum prolactin levels through maintenance treatment phase and follow-up period were assessed between groups and within groups. RESULTS: Except for group I, all the groups showed a similar pattern with fast decrease of serum prolactine level during maintenance phase and slower increase during the follow up period. Notably, the average prolactin level was significantly lower at the last follow-up visit than at the diagnosis time in all of the groups. Stable normoprolactinemia of the groups at the end of follow-up period were 47.2, 37, 48.7, and 34.9%, respectively. CONCLUSIONS: The results indicate that short maintenance treatment in idiopathic and microadenoma-related hyperprolactinemia seems as effective as long maintenance treatment in the present study. But, further studies with larger study population and longer follow-up period are needed to make a decision about early treatment withdrawal. Also, during the maintenance treatment administration of medicine to patients should be tapered down to the lowest dose that will maintain prolactin levels normal. PMID- 20571821 TI - Mitochondrial gene expression in elite cyclists: effects of high-intensity interval exercise. AB - Little is known about the effect of training on genetic markers for mitochondrial biogenesis in elite athletes. We tested the hypothesis that low-volume sprint interval exercise (SIE) would be as effective as high-volume interval exercise (IE). Ten male cyclists competing on national elite level (W (max) 403 +/- 13 W, VO(2peak) 68 +/- 1 mL kg(-1) min(-1)) performed two interval exercise protocols: 7 * 30-s "all-out" bouts (SIE) and 3 * 20-min bouts at ~87% of VO(2peak) (IE). During IE, the work was eightfold larger (1,095 +/- 43 vs. 135 +/- 5 kJ) and the exercise duration 17 times longer (60 vs. 3.5 min) than during SIE. Muscle samples were taken before and 3 h after exercise. The mRNA of upstream markers of mitochondrial biogenesis [peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha), PGC-1alpha-related coactivator (PRC) and peroxisome proliferator-activated receptor delta (PPARdelta)] increased to the same extent after SIE and IE (6-, 1.5- and 1.5-fold increase, respectively). Of the downstream targets of PGC-1alpha, mitochondrial transcription factor A (Tfam) increased only after SIE and was significantly different from that after IE (P < 0.05), whereas others increased to the same extent (pyruvate dehydrogenase kinase, PDK4) or was unchanged (nuclear respiratory factor 2, NRF2). We conclude that upstream genetic markers of mitochondrial biogenesis increase in a similar way in elite athletes after one exercise session of SIE and IE. However, since the volume and duration of work was considerably lower during SIE and since Tfam, the downstream target of PGC-1alpha, increased only after SIE, we conclude that SIE might be a time-efficient training strategy for highly trained individuals. PMID- 20571822 TI - Analysis of sprint cross-country skiing using a differential global navigation satellite system. AB - The purpose was to examine skiing velocities, gear choice (G2-7) and cycle rates during a skating sprint time trial (STT) and their relationships to performance, as well as to examine relationships between aerobic power, body composition and maximal skiing velocity versus STT performance. Nine male elite cross-country skiers performed three tests on snow: (1) Maximum velocity test (V (max)) performed using G3 skating, (2) V (max) test performed using double poling (DP) technique and (3) a STT over 1,425 m. Additional measurements of VO(2max) during roller skiing and body composition using iDXA were made. Differential global navigation satellite system data were used for position and velocity and synchronized with video during STT. The STT encompassed a large velocity range (2.9-12.9 m s(-1)) and multiple transitions (21-34) between skiing gears. Skiing velocity in the uphill sections was related to gear selection between G2 and G3. STT performance was most strongly correlated to uphill time (r = 0.92, P < 0.05), the percentage use of G2 (r = -0.72, P < 0.05), and DP V (max) (r = -0.71, P < 0.05). The velocity decrease in the uphills from lap 1 to lap 2 was correlated with VO(2max) (r = -0.78, P < 0.05). V (max) in DP and G3 were related to percent of racing time using G3. In conclusion, the sprint skiing performance was mainly related to uphill performance, greater use of the G3 technique, and higher DP and G3 maximum velocities. Additionally, VO(2max) was related to the ability to maintain racing velocity in the uphills and lean body mass was related to starting velocity and DP maximal speed. PMID- 20571823 TI - Modulation of Ca(2+) release through ryanodine receptors in vascular smooth muscle by protein kinase Calpha. AB - The role of protein kinase C (PKC) in Ca(2+) release through ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) of vascular smooth muscle cells (SMCs) is not well understood. Caffeine was used to activate RyRs and the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured in both freshly isolated and cultured mouse aortic SMCs (ASMCs). Pre-activation of PKC with 1,2-dioctanoyl-sn glycerol (DOG) prevented caffeine-induced [Ca(2+)](i) transients. Application of the PKC inhibitor calphostin C caused [Ca(2+)](i) transients which were not blocked by nifedipine or by removing extracellular Ca(2+) but were abolished after inhibition of the SR Ca(2+)-ATPase with thapsigargin or after inhibition of RyRs with ryanodine. In addition, chelerythrine and GF109203X also elevated resting [Ca(2+)](i) but no further [Ca(2+)](i) increase was seen with subsequent application of caffeine. Selective inhibition of PKCalpha with safingol blocked caffeine-induced [Ca(2+)](i) transients, but the PKCepsilon inhibitory peptide V1 2 did not. In cells expressing a EGFP-tagged PKCalpha, caffeine-induced [Ca(2+)](i) transients were associated with a rapid focal translocation near the cell periphery, while application of ionomycin and DOG caused translocation to the plasma membrane. Western blot showed that caffeine increased the relative amount of PKCalpha in the particulate fraction in a time-dependent manner. Co immunoprecipitation of RyRs and PKCalpha indicated that they interact. In conclusion, our studies suggest that PKC activation can inhibit the gating activity of RyRs in the SR of ASMCs, and this regulation is most likely mediated by the Ca(2+)-dependent PKCalpha isoform. PMID- 20571824 TI - Expression analysis of the auxin efflux carrier family in tomato fruit development. AB - Auxin transport network, which is important in the integration of plant developmental signals, depends on differential expression of the auxin efflux carrier PIN gene family. We cloned three tomato PIN (referred as SlPIN) cDNAs and examined their expression patterns in fruit and other organs. The expression of SlPIN1 and SlPIN2 was highest in very young fruit immediately after anthesis, whereas the expression of SlPIN3 was low at this same stage of fruit development. SlPIN2::GUS was expressed in ovules at anthesis and in young developing seeds at 4 days after anthesis, while SlPIN1::GUS was expressed in whole fruit. The DR5::GUS auxin-responsive reporter gene was expressed in the fruit and peduncle at anthesis and was higher in the peduncle 4 days after anthesis. These studies suggest that auxin is likely transported from young seeds by SlPIN1 and SlPIN2 and accumulated in peduncles where SlPIN gene expression is low in tomato. The possible role of SlPINs in fruit set was discussed. PMID- 20571825 TI - Clinical practice: drug desensitization in children. AB - Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids. PMID- 20571826 TI - Clinical practice. Protein-losing enteropathy in children. AB - Protein-losing enteropathy (PLE) is a rare complication of a variety of intestinal disorders characterized by an excessive loss of proteins into the gastrointestinal tract due to impaired integrity of the mucosa. The clinical presentation of patients with PLE is highly variable, depending upon the underlying cause, but mainly consists of edema due to hypoproteinemia. While considering PLE, other causes of hypoproteinemia such as malnutrition, impaired synthesis, or protein loss through other organs like the kidney, liver, or skin, have to be excluded. The disorders causing PLE can be divided into those due to protein loss from intestinal lymphatics, like primary intestinal lymphangiectasia or congenital heart disease and those with protein loss due to an inflamed or abnormal mucosal surface. The diagnosis is confirmed by increased fecal concentrations of alpha-1-antitrypsin. After PLE is diagnosed, the underlying cause should be identified by stool cultures, serologic evaluation, cardiac screening, or radiographic imaging. Treatment of PLE consists of nutrition state maintenance by using a high protein diet with supplement of fat-soluble vitamins. In patients with lymphangiectasia, a low fat with medium chain triglycerides (MCT) diet should be prescribed. Besides dietary adjustments, appropriate treatment for the underlying etiology is necessary and supportive care to avoid complications of edema. PLE is a rare complication of various diseases, mostly gastrointestinal or cardiac conditions that result into loss of proteins in the gastrointestinal tract. Prognosis depends upon the severity and treatment options of the underlying disease. PMID- 20571827 TI - CRABP1-reduced expression is associated with poorer prognosis in serous and clear cell ovarian adenocarcinoma. AB - PURPOSE: CRABP1 is a modulator of retinoic acid function. The aim of the present study was to investigate CRABP1 expression and its clinical significance in ovarian carcinoma. METHODS: Expression of CRABP1 protein was investigated by immunohistochemical analysis in 100 ovarian carcinomas of various histological sub-types, including serous and clear cell adenocarcinomas. Relationship of CRABP1 expression to clinical features, including prognosis, was analyzed. RESULTS: Reduced expression of CRABP1 protein was detected especially frequently in the serous and clear cell adenocarcinomas sub-types, 50% (20 of 40) and 38% (10 of 26) of cases, respectively. We found that in both serous and clear cell adenocarcinomas overall survival was significantly poorer in the cases with reduced CRABP1 expression compared to similar cases where expression was maintained, irrespective of the disease stage (P = 0.0073 and 0.049, respectively). Disease-free survival of the serous and clear cell adenocarcinoma cases with reduced CRABP1 expression was significantly poorer, compared to the cases whose CRABP1 expression was maintained (P = 0.024). Multivariate analysis showed that reduced expression of CRABP1 was a significantly important prognostic factor (adjusted hazard ratio: 8.189 (95% CI, 2.186-30.672, P = 0.0019)). CONCLUSIONS: The present study is the first to demonstrate that the reduced expression of CRABP1 has a potential as a prognostic marker for serous adenocarcinoma which is the most frequent histological ovarian tumor type and also for clear cell carcinoma that often exhibits chemo-resistance. Further study is necessary to clarify how CRABP1 protein expression was altered and how CRABP1 affects ovarian carcinoma cells. PMID- 20571828 TI - Proliferative cell types in embryonic lineages of the central complex of the grasshopper Schistocerca gregaria. AB - The central complex of the grasshopper Schistocerca gregaria develops to completion during embryogenesis. A major cellular contribution to the central complex is from the w, x, y, z lineages of the pars intercerebralis, each of which comprises over 100 cells, making them by far the largest in the embryonic protocerebrum. Our focus has been to find a cellular mechanism that allows such a large number of cell progeny to be generated within a restricted period of time. Immunohistochemical visualization of the chromosomes of mitotically active cells has revealed an almost identical linear array of proliferative cells present simultaneously in each w, x, y, z lineage at 50% of embryogenesis. This array is maintained relatively unchanged until almost 70% of embryogenesis, after which mitotic activity declines and then ceases. The array is absent from smaller lineages of the protocerebrum not associated with the central complex. The proliferative cells are located apically to the zone of ganglion mother cells and amongst the progeny of the neuroblast. Comparisons of cell morphology, immunoreactivity (horseradish peroxidase, repo, Prospero), location in lineages and spindle orientation have allowed us to distinguish the proliferative cells in an array from neuroblasts, ganglion mother cells, neuronal progeny and glia. Our data are consistent with the proliferative cells being secondary (amplifying) progenitors and originating from a specific subtype of ganglion mother cell. We propose a model of the way that neuroblasts, ganglion mother cells and secondary progenitors together produce the large cell numbers found in central complex lineages. PMID- 20571829 TI - Diverging climate trends in Mongolian taiga forests influence growth and regeneration of Larix sibirica. AB - Central and semiarid north-eastern Asia was subject to twentieth century warming far above the global average. Since forests of this region occur at their drought limit, they are particularly vulnerable to climate change. We studied the regional variations of temperature and precipitation trends and their effects on tree growth and forest regeneration in Mongolia. Tree-ring series from more than 2,300 trees of Siberian larch (Larix sibirica) collected in four regions of Mongolia's forest zone were analyzed and related to available weather data. Climate trends underlie a remarkable regional variation leading to contrasting responses of tree growth in taiga forests even within the same mountain system. Within a distance of a few hundred kilometers (140-490 km), areas with recently reduced growth and regeneration of larch alternated with regions where these parameters remained constant or even increased. Reduced productivity could be correlated with increasing summer temperatures and decreasing precipitation; improved growth conditions were found at increasing precipitation, but constant summer temperatures. An effect of increasing winter temperatures on tree-ring width or forest regeneration was not detectable. Since declines of productivity and regeneration are more widespread in the Mongolian taiga than the opposite trend, a net loss of forests is likely to occur in the future, as strong increases in temperature and regionally differing changes in precipitation are predicted for the twenty-first century. PMID- 20571830 TI - Quantitative metabolic flux analysis revealed uneconomical utilization of ATP and NADPH in Acremonium chrysogenum fed with soybean oil. AB - A metabolic network was constructed for the Acremonium chrysogenum cultivation fed with soybean oil. Metabolic flux analysis indicated that the shift from exponential growth to rapid cephalosporin C (CPC) formation was accompanied by 1.63- and 5-fold carbon flux enlargement in TCA cycle and glyoxylate by-pass, respectively. The flux via pentose phosphate pathway branch was little affected during the rapid CPC formation period; the contributory explanation was that 35.6% of NADPH was consumed in the dissimilation of fatty acids. Estimation of NADPH, ATP generation, and consumption demonstrated that, with soybean oil as carbon source in rapid CPC formation phase, the NADPH consumed in fatty acid catabolism was fourfold greater than that used in the CPC biosynthesis-relevant part; simultaneously, more than 90% energy spent was not directly related to the CPC formation. Therefore, the improvement of CPC production yield through optimization of the NADPH, ATP generation, and consumption was put forward. PMID- 20571831 TI - Comparison of the actions of acylated and desacylated ghrelin on acid secretion in the rat stomach. AB - BACKGROUND: Ghrelin, a growth-hormone-releasing peptide, has two major molecular forms: acylated (acyl) and desacylated (desacyl). Recent studies suggest different roles for these two forms. In the present study, we compared desacyl and acyl ghrelin with regard to acid secretion and histamine production in the rat stomach. METHODS: We performed in vivo experiments using gastric lumen perfused rats. The effects of the two forms of ghrelin on gastrin (gastrin-17) stimulated acid secretion were also examined. Furthermore, to examine the effects of ghrelin on histamine production, histidine decarboxylase messenger ribonucleic acid in the gastric corpus mucosa was measured by reverse transcription polymerase chain reaction. RESULTS: Intravenous administration of acyl ghrelin at 20 MUg/kg increased gastric acid secretion to 4.8 times greater than control levels. However, desacyl ghrelin had no effect on acid secretion, even at 200 MUg/kg. Acyl ghrelin enhanced gastrin-stimulated acid secretion while desacyl ghrelin did not. Vagotomy markedly inhibited the enhancement of gastrin stimulated acid secretion by acyl ghrelin. Acyl ghrelin increased histidine decarboxylase messenger ribonucleic acid concentration by 2.3 times compared with basal levels at 1 h after administration and by 2.7 times at 2 h after administration; desacyl ghrelin had no such effect. Synergism between acyl ghrelin and gastrin was seen regarding histidine decarboxylase messenger ribonucleic acid concentration. CONCLUSIONS: The results indicate that acyl ghrelin stimulates gastric acid secretion via a mechanism involving activation of the vagus nerve and histamine release and synthesis and that desacyl ghrelin has no action on gastric acid secretion. Furthermore, the results demonstrate synergism between gastrin and acyl ghrelin in terms of gastric acid secretion via a mechanism involving histamine release and synthesis. PMID- 20571832 TI - Intraarticular levobupivacaine or bupivacaine administration decreases pain scores and provides a better recovery after total knee arthroplasty. AB - PURPOSE: The aim of this prospective randomized blinded controlled study was to compare the efficacy of the two local anesthetics, intraarticular bupivacaine and levobupivacaine administration, versus control for postoperative pain control and functional recovery. Length of hospital stay, opioid consumption, and the side effects of opioids were also evaluated. METHODS: Sixty patients of American Society of Anesthesiologists class I-III undergoing elective knee arthroplasty under spinal anesthesia were randomized into three groups. Groups B (n = 20) and L (n = 20) both received 150 ml solution intraarticularly, containing 200 mg bupivacaine or 200 mg levobupivacaine combined with 0.5 mg epinephrine, respectively, at the end of the surgery. Group C (n = 20) received 150 ml saline intraarticularly. Postoperatively, all groups received injections through the intraarticular catheters in quantities of 120 mg (levobupivacaine for group L, bupivacaine for group B) and 0.5 mg epinephrine whereas group C received a saline bolus at 10 and 22 h. Patients were given tramadol by intravenous patient controlled analgesia (PCA), and sodium diclofenac 75 mg intramuscularly was used for rescue analgesic medication. Visual analogue score (VAS) for pain at rest and during mobilization (which was defined as flexion exercise supported by physiotherapist in postoperative first 8 h and afterward a 3-m walk with walker), consumption of tramadol, side effects, and patient satisfaction were recorded until the 48th hour postoperatively. RESULTS: Area under the curve values for VAS were lower in groups B and L compared to the control, both at rest and during mobilization (first 48 h) (P = 0.032 and P = 0.029, respectively). Tramadol consumption was lower (P < 0.05), patient satisfaction as evaluated with a five point Likert score (completely comfortable; quite comfortable; slight discomfort; painful; very painful) was higher (P = 0.03), and length of hospital stay was shorter (P = 0.03) in groups B and L compared to group C. CONCLUSION: Intraarticular bupivacaine and levobupivacaine provided better postoperative analgesia both at rest and during mobilization in total knee replacement surgery compared to control. Tramadol consumption and hospital stay were also decreased in the study groups. PMID- 20571833 TI - Unique arbuscular mycorrhizal fungal communities uncovered in date palm plantations and surrounding desert habitats of Southern Arabia. AB - The main objective of this study was to shed light on the previously unknown arbuscular mycorrhizal fungal (AMF) communities in Southern Arabia. We explored AMF communities in two date palm (Phoenix dactylifera) plantations and the natural vegetation of their surrounding arid habitats. The plantations were managed traditionally in an oasis and according to conventional guidelines at an experimental station. Based on spore morphotyping, the AMF communities under the date palms appeared to be quite diverse at both plantations and more similar to each other than to the communities under the ruderal plant, Polygala erioptera, growing at the experimental station on the dry strip between the palm trees, and to the communities uncovered under the native vegetation (Zygophyllum hamiense, Salvadora persica, Prosopis cineraria, inter-plant area) of adjacent undisturbed arid habitat. AMF spore abundance and species richness were higher under date palms than under the ruderal and native plants. Sampling in a remote sand dune area under Heliotropium kotschyi yielded only two AMF morphospecies and only after trap culturing. Overall, 25 AMF morphospecies were detected encompassing all study habitats. Eighteen belonged to the genus Glomus including four undescribed species. Glomus sinuosum, a species typically found in undisturbed habitats, was the most frequently occurring morphospecies under the date palms. Using molecular tools, it was also found as a phylogenetic taxon associated with date palm roots. These roots were associated with nine phylogenetic taxa, among them eight from Glomus group A, but the majority could not be assigned to known morphospecies or to environmental sequences in public databases. Some phylogenetic taxa seemed to be site specific. Despite the use of group-specific primers and efficient trapping systems with a bait plant consortium, surprisingly, two of the globally most frequently found species, Glomus intraradices and Glomus mosseae, were not detected neither as phylogenetic taxa in the date palm roots nor as spores under the date palms, the intermediate ruderal plant, or the surrounding natural vegetation. The results highlight the uniqueness of AMF communities inhabiting these diverse habitats exposed to the harsh climatic conditions of Southern Arabia. PMID- 20571834 TI - Polymorphisms in TGFB1 and PDGFRB are associated with Moyamoya disease in European patients. AB - BACKGROUND: The etiology of Moyamoya disease (MMD) is still widely unknown. Several publications on Moyamoya describe differences of cytokine and growth factor concentrations in different specimen. We analyzed the DNA of patients with MMD for single nucleotide polymorphisms (SNPs) in and upstream of the genes for previously described associated cytokines and growth factors. METHOD: Thirteen SNPs were genotyped in or upstream to four genes-basic fibroblast growth factor (BFGF), cellular retinoic acid-binding protein 1 (CRABP1), platelet derived growth factor receptor beta (PDGFRB), and transforming growth factor beta 1 (TGFB1)-comparing 40 DNA samples of MMD patients to 68 healthy controls from central Europe. Genotyping was performed by sequencing the SNP-containing genetic regions with custom made primers. FINDINGS: We found association of two SNPs: rs382861 [A/C] (p = 0.0373, OR = 1.81, 95% CI = 1.03-3.17) in the promoter region of PDGFRB and rs1800471[C/G] (p = 0.0345, OR = 7.65, 95% CI = 0.97-59.95), located in the first exon of TGFB1. CONCLUSION: Our results indicate possible genetic risk factors for the genesis of MMD. TGFB1 and PDGFRB are involved in vascular growth and transformation processes which may play a role in the development of MMD. Further analyses in larger European cohorts and replication in patients of different ethnicity, as well as functional studies, may lead to possible early detection of patients at risk for developing MMD and subsequently to future preventive therapies. PMID- 20571835 TI - Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells. AB - BACKGROUND: Because adipose-tissue-derived stromal cell (ADSC) is readily accessible and abundant in stem cell, ADSC may be a better candidate for cell therapy and tissue engineering. This study investigated the potential of ADSC implantation to restore disc in a rat IVD model. METHODS: The first coccygeal disc segments of a Sprague-Dawley rat was left undamaged as a control (NC) group, and other two segments were damaged by needle injection. Two weeks later, ADSCs (TS) group or saline (IN) group was transplanted into each of the two damaged segments. RESULTS: At 6 weeks after transplantation, the TS group showed a significantly smaller reduction in disc height than the IN group and exhibited a restoration of MRI signal intensity. Hematoxylin and eosin staining revealed a greater restoration of the inner annulus structure in the TS group. Anti-Human Nucleic Antibody, collagen type II, and aggrecan, staining showed positive findings at 2 weeks after transplantation in TS group. CONCLUSIONS: ADSCs show potential for restoring degenerative discs and may prove effective in the treatment of IVD. PMID- 20571836 TI - Inflammation induced neurological handicap processes in multiple sclerosis: new insights from preclinical studies. AB - Multiple sclerosis (MS) is described as originating from incompletely explained neuroinflammatory processes, dysfunction of neuronal repair mechanisms and chronicity of inflammation events. Blood-borne immune cell infiltration and microglia activation are causing both neuronal destruction and myelin loss, which are responsible for progressive motor deficiencies, organic and cognitive dysfunctions. MRI as a non-invasive imaging method offers various ways to visualise de- and remyelination, neuronal loss, leukocyte infiltration, blood brain barrier modification and new sensors are emerging to detect inflammatory lesions at an early stage. We describe studies performed on experimental autoimmune encephalomyelitis (EAE) animal models of MS that shed new light on mechanisms of functional impairments to understand the neurological handicap in MS. We focus on examples of neuroinflammation-mediated inhibition of CNS repair involving adult neurogenesis in the sub-ventricular zone and hippocampus and such experimentally observed inhibitions could reflect deficient plasticity and activation of compensatory mechanisms in MS. In parallel with cognitive decline, organic deficits such as bladder dysfunction are described in most of MS patients. Neuropharmacological interventions, electrical stimulation of nerves, MRI and histopathology follow-up studies helped in understanding the operating events to remodel the neurological networks and to compensate the inflammatory lesions both in spinal cord and in cortical regions. At the molecular level, the local production of reactive products is a well-described phenomenon: oxidative species disturb cellular physiology and generate new molecular epitopes that could further promote immune reactions. The translational research from EAE animal models to MS patient cohorts helps in understanding the mechanisms of the neurological handicap and in development of new therapeutic concepts in MS. PMID- 20571838 TI - Status of foot-and-mouth disease in Pakistan. AB - The present study reports the distribution of different serotypes of foot-and mouth disease virus (FMDV) in Pakistan during the period 1952-2007. During this time, a total of 1,543 epithelial samples out of 2,484 tested were found positive for various serotypes of FMDV. Serotype O was found to be the most prevalent (p < 0.001) followed by serotype Asia-1 and A. Serotype C was detected only in 1954, 1963 and 1995. The disease was found to be more prevalent (p < 0.0001) in cattle than buffaloes. The geographical distribution of 153 laboratory confirmed FMD outbreaks from 2002 to 2007 and the serotypes of the virus involved has been mapped. Higher number of outbreaks of the disease was noted between the months of January to March during this period, which may be attributed to the livestock movement in the country particularly due to religious festival, Eidul Azha, in which the animals are sacrificed. PMID- 20571839 TI - Dengue-2-virus-interacting polypeptides involved in mosquito cell infection. AB - For the design of effective antiviral strategies, understanding the fundamental steps of the virus life cycle, including virus-host interactions, is essential. We performed a virus overlay protein binding assay followed by proteomics for identification of proteins from membrane fractions of A7 (Aedes aegypti) cells, C6/36 (Aedes albopictus) cells and the midgut brush border membrane fraction of Ae. aegypti mosquito that bind to dengue-2 virus. Actin, ATP synthase beta subunit, HSc 70, orisis, prohibitin, tubulin beta chain, and vav-1 were identified as dengue-2-virus-binding proteins. Our results suggest that dengue-2 virus exploits an array of housekeeping proteins for its entry in mosquito cells. PMID- 20571837 TI - Neuroinflammation is a key player in Parkinson's disease and a prime target for therapy. AB - Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Increasing evidence has demonstrated that inflammation is the fundamental process contributing to neuron death in PD. Neuroinflammation, which is characterized by activated microglia and infiltrating T cells at sites of neuronal injury, is a prominent contributor to the pathogenesis of progressive PD. Microglia play a critical role in forming a self-propelling cycle leading to sustained chronic neuroinflammation and driving the progressive neurodegeneration in PD. This activation depends heavily on the respiratory burst within the microglia, which in turn regulates a number of downstream pro-inflammatory activities. On the other hand, the adaptive immune responses, most notably T cells, are now emerging as important components of the inflammatory response that contribute to the pathogenesis of PD. This review paper focus on the understanding of the inflammatory etiology of PD, as well as the molecular signaling involved in this inflammatory response, with the aim to provide more effective treatments to slow down or halt the progression of chronic inflammation induced CNS disorders, such as PD. PMID- 20571840 TI - Synthesis of soluble poly(amide-ether-imide-urea)s bearing amino acid moieties in the main chain under green media (ionic liquid). AB - In this study, an optically active diamine, N,N'-(pyromellitoyl)-bis{N-[4(4 aminophenoxy)phenyl]-2-(4-methyl)pentanamide} (1) containing amino acid L-leucine was prepared in three steps. The step-growth polymerization of this chiral diamine with several diisocyanates in room temperature ionic liquid (IL), 1,3 dipropylimidazolium bromide as an environmentally friendly solvent and in a volatile organic solvent, is investigated. The polymerization yields and inherent viscosities of the resulting poly(amide-ether-imide-urea)s are compared in both solvents. The results show that the IL to be the superior polymerization media. All of the obtained polymers exhibited good solubility in some polar aprotic organic solvents such as N,N-dimethyacetamide, N,N-dimethyformamide, dimethyl sulfoxide while thermal stability was not disturbed based on thermogravimetric analysis and differential scanning calorimetry experiments. X-ray diffraction analysis of polymers shows that they are amorphous. The observation of optical rotation confirms the optical activity of prepared polymers. PMID- 20571841 TI - Memantine reduces consumption of highly palatable food in a rat model of binge eating. AB - Excessive consumption of highly palatable food has been linked to the development of eating disorders and obesity, and can be modeled in non-food-deprived rats by offering them a limited (2-h daily) access to an optional dietary fat. Since the glutamatergic system has recently emerged as a viable target for binge-eating medication development, we compared the effects of subchronic treatment with glutamatergic receptor antagonists to the effects of a reference appetite suppressing agent sibutramine on highly palatable food (lard) and normal chow intake. In three separate experiments, the consumption of a standard laboratory chow and lard were measured during 12 days of medication treatment and for 6 days afterwards. Generalized estimating equations analysis demonstrated that sibutramine (7.5 mg/kg, p.o.) significantly decreased lard consumption, with a concurrent increase in chow consumption. Sibutramine effects disappeared after treatment discontinuation. The NMDA receptor antagonist memantine (5 mg/kg, i.p.) significantly decreased lard consumption and increased chow consumption, comparable to effects of sibutramine; however, memantine's effects persisted after treatment discontinuation. The effects of the mGluR5 antagonist MTEP (7.5 mg/kg, i.p.) on food consumption were in the same direction as seen with memantine, but the observed differences were not significant. In an additional control experiment, sibutramine and memantine reduced unlimited (24 h) chow intake during the treatment phase. Present results provide evidence that glutamatergic neurotransmission might be involved in the regulation of excessive consumption of highly palatable foods, and suggest that NMDA receptor may be an attractive target for developing obesity and disordered eating pharmacotherapies. PMID- 20571842 TI - Two intracellular helices of G-protein coupling receptors could generally support oligomerization and coupling with transducers. AB - For many G-protein coupling receptors (GPCRs), the upkeep of receptor dimers could depend on association with functional Gi alpha subunits. This is known for Y1, Y2 and Y4 neuropeptide Y receptors [presented in the companion paper (Estes et al., Amino Acids, doi: 10.1007/s00726-010-0642-z , 2010)]. Interactions with transducers use mainly intracellular domains of the receptors. Intracellular loops 1 and 2 in GPCRs are short and lack extensive helicity that could support transducer anchoring. Interaction with G-proteins is known to use the juxtamembrane Helix 8 in the fourth intracellular domain, for which we document a helix-stabilizing n/(n + 4) pattern of large hydrophobic sidechains. Another intracellular helix located in the C-terminal portion of the third intracellular loop does not display a strong stabilizing pattern, and is found in many studies to serve dynamically in association and activation of transducers and effectors. We show that these tracts share features across metazoan phyla not only in opsins and opsin-like receptors (including the Y receptors), but also in Taste-2 and Frizzled receptors. Similarities of these helices across GPCR groups could have both phylogenetic and functional roots. PMID- 20571843 TI - Periodontal surgery in furcation-involved maxillary molars revisited--an introduction of guidelines for comprehensive treatment. AB - Maxillary molars with interradicular loss of periodontal tissue have an increased risk of additional attachment loss with an impaired long-term prognosis. Since accurate clinical analysis of furcation involvement is not feasible due to limited access, morphological variations and measurement errors, additional diagnostics, e.g., with cone-beam computed tomography, may be required. Surgical treatment options have graduated from a less invasive approach, i.e., keeping as much periodontal attachment as possible, to a more invasive approach: (1) open flap debridement with/without gingivectomy or apically repositioned flap and/or tunnelling; (2) root separation; (3) amputation/trisection of a root (with/without root separation or tunnel preparation); (4) amputation/trisection of two roots; and (5) extraction of the entire tooth. Tunnelling is indicated when the degree of root separation allows for opening of the interradicular region. Alternatively, root separation is performed particularly in root-canal treated teeth with reduced coronal tooth substance requiring crown restorations. As soon as the attachment of one or two roots in maxillary molars is severely reduced, root removal is indicated and performed either as amputation or trisection including the corresponding part of the clinical crown. While the indication for regenerative measures in maxillary molars with furcation involvement is very limited, extraction and replacement with implants is restricted, particularly in sites requiring complex alveolar ridge augmentation and sinus elevation. A systematic approach for decision making in furcation involved maxillary molars is described in this overview, including what constitutes accurate diagnosis and what indications there are for the different surgical periodontal treatment options. PMID- 20571844 TI - Design of 1-arylsulfamido-2-alkylpiperazine derivatives as secreted PLA2 inhibitors. AB - Structure and analog based analysis of 3D-QSAR, CoMFA and CoMSIA, along with different docking protocols were used to evaluate the structure activity relationship of 26 analogues of 1-aryl sulfamido-2-alkyl piperazines to model the activities of group I and II secreted phospholipases A(2) (sPLA(2)s) and probe into the chemical space and nature of receptor--ligand interactions. The best CoMFA model yields cross-validated (q(2)) and conventional correlation coefficients (r(2)) of 0.703 and 0.962 respectively whereas CoMSIA model yields q(2) and r(2) values of 0.408 and 0.922 respectively, followed by docking analysis using FlexX and GOLD methodologies on the X-ray structure of human and bovine PLA(2)s. A comparative study was made to find out the differences in the active site residues of both PLA(2)s. The information enunciated from the analysis of CoMFA and CoMSIA maps and docking results were analyzed and employed in the design of 29 new ligands using molecules 4, 21, 22 from the initial set as templates. New ligands for group I and II secreted phospholipases A(2) (sPLA(2)s) have been thus designed based on the 32 analogues of 1-aryl sulfamido-2-alkyl piperazine with a cursory note on its synthetic feasibility. Molecular modeling studies indicate that the newly designed ligands are expected to show high affinity and experimental efforts in this direction is highly rewarding. PMID- 20571845 TI - Recombinant human bone morphogenetic protein-2 (rhBMP-2) in the treatment of mandibular sequelae after tumor resection. AB - BACKGROUND: Ameloblastoma is a locally aggressive tumor most often found in posterior body and angle of the mandible. Although ameloblastoma has histological characteristics of benignity, they have a high percentage of local recurrence and possible malignant development if treated improperly. CASE REPORT: This report presents a treatment of unusual mandibular sequelae after tumor resection using recombinant human bone morphogenetic protein-2 (rhBMP-2) associated with hydroxyapatite (HA) and calcium triphosphate (TCP). DISCUSSION: Seven months after surgery, the patient was asymptomatic, with stable occlusion and class I, without signs of infection or rejection, and bone repair with rigidity compatible to an immature bone structure was observed. Reconstruction of large mandibular bone defect with a combination of rhBMP-2 and HA/TCP achieving a satisfactory result with less invasive and minimum morbidity has been demonstrated. PMID- 20571846 TI - Atypical multifocal hydatid disease of cranial vault: simultaneous orbital and extradural meningeal involvement. AB - Hydatid disease is endemic in regions where livestock is raised. Liver and lungs are the most commonly affected organs by the disease. Cranial vault and orbital hydatid disease is extremely rare. Signs and symptoms along with serological investigation are often inconclusive in cranial hydatid, making radiological diagnosis extremely important. Surgical removal of the cyst is the mainstay of treatment. Postoperative medical therapy, along with regular follow-up, is the key to detect any recurrence. We report an unusual case of cranial hydatid which showed diffuse scalp infiltration along with orbital and extradural extension. PMID- 20571848 TI - Competition between folding and aggregation in a model for protein solutions. AB - We study the thermodynamic and kinetic consequences of the competition between single-protein folding and protein-protein aggregation using a phenomenological model, in which the proteins can be in the unfolded (U), misfolded (M) or folded (F) states. The phase diagram shows the coexistence between a phase with aggregates of misfolded proteins and a phase of isolated proteins (U or F) in solution. The spinodal at low protein concentrations shows non-monotonic behavior with temperature, with implications for the stability of solutions of folded proteins at low temperatures. We follow the dynamics upon "quenching" from the U phase (cooling) or the F-phase (heating) to the metastable or unstable part of the phase diagram that results in aggregation. We describe how interesting consequences to the distribution of aggregate size, and growth kinetics arise from the competition between folding and aggregation. PMID- 20571847 TI - Quantitative predictions on auxin-induced polar distribution of PIN proteins during vein formation in leaves. AB - The dynamic patterning of the plant hormone auxin and its efflux facilitator the PIN protein are the key regulators for the spatial and temporal organization of plant development. In particular auxin induces the polar localization of its own efflux facilitator. Due to this positive feedback, auxin flow is directed and patterns of auxin and PIN arise. During the earliest stage of vein initiation in leaves auxin accumulates in a single cell in a rim of epidermal cells from which it flows into the ground meristem tissue of the leaf blade. There the localized auxin supply yields the successive polarization of PIN distribution along a strand of cells. We model the auxin and PIN dynamics within cells with a minimal canalization model. Solving the model analytically we uncover an excitable polarization front that triggers a polar distribution of PIN proteins in cells. As polarization fronts may extend to opposing directions from their initiation site, we suggest a possible resolution to the puzzling occurrence of bipolar cells, thus we offer an explanation for the development of closed, looped veins. Employing non-linear analysis, we identify the role of the contributing microscopic processes during polarization. Furthermore, we deduce quantitative predictions on polarization fronts establishing a route to determine the up to now largely unknown kinetic rates of auxin and PIN dynamics. PMID- 20571850 TI - Aggression does not increase friendly contacts among bystanders in geladas (Theropithecus gelada). AB - Aggression within a social group may affect bystanders' affinitive behaviour with other bystanders. After a conflict such affiliations, termed 'quadratic', may serve to reduce tension. This particular kind of conflict management has been found in hamadryas baboons. Following the classical and well-established approach for studying post-conflict behaviour [post-conflict/matched control method (PC/MC)], we collected behavioural data on a group of geladas (Theropithecus gelada) in order to check for the presence of quadratic affiliations. A total of 192 PC/MC pairs were collected on both adults and immature individuals. We did not find any increase of affiliation levels between bystanders during PC compared with MC condition. The distribution of affinitive quadratic interactions was not affected by either kinship or relationship quality of bystanders. Moreover, comparison of yawning and self-scratching behaviours (two of the typical non primate displacement activities under stressful situations) recorded during PCs and MCs did not show any variation in the two conditions. Probably, due to the male tolerance and social cohesiveness in geladas, witnessing a fight does not necessarily induce a sufficient increase of tension in bystanders to be reduced by quadratic affiliation. PMID- 20571849 TI - Re: PanCanadian evaluation of irreversible compression ratios ("lossy" compression) for development of national guidelines. PMID- 20571851 TI - Investigation of age-related changes in physiological kinetic tremor. AB - Tremor is the most common movement disorder characterized by repetitive and stereotyped movements. Most investigations on tremor attempt to understand its relation to neuromuscular dysfunctions. Therefore, there is a lack of studies that aim to investigate the complex relation between the physiological tremor and aging, especially in kinetic conditions. In this context, the main motivation of this research was to quantify age-related changes in the kinetic tremor of clinically healthy individuals. For this, a number of features extracted from tremor activity, obtained from digitized drawings of Archimedes' spirals, were analyzed. In total, 59 subjects participated in the experiments. These individuals were divided into seven groups according to their ages and two types of analysis were carried out. First, the tremor activity of young and elderly adults was investigated by means of traditional features commonly used in tremor analysis, and secondly, linear discriminant analysis (LDA) was employed for the study of the correlation between age and tremor. The results showed significant statistical differences between the kinetic tremor activity of the young and elderly groups. Furthermore, it was found that LDA allowed for the estimate of a unique feature, so-called LDA-value, which showed to be linearly correlated with age. PMID- 20571852 TI - Numerical investigation of the performance of three hinge designs of bileaflet mechanical heart valves. AB - Thromboembolic complications (TECs) of bileaflet mechanical heart valves (BMHVs) are believed to be due to the nonphysiologic mechanical stresses imposed on blood elements by the hinge flows. Relating hinge flow features to design features is, therefore, essential to ultimately design BMHVs with lower TEC rates. This study aims at simulating the pulsatile three-dimensional hinge flows of three BMHVs and estimating the TEC potential associated with each hinge design. Hinge geometries are constructed from micro-computed tomography scans of BMHVs. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Leaflet motion and flow boundary conditions are extracted from fluid-structure-interaction simulations of BMHV bulk flow. The numerical results are analyzed using a particle-tracking approach coupled with existing blood damage models. The gap width and, more importantly, the shape of the recess and leaflet are found to impact the flow distribution and TEC potential. Smooth, streamlined surfaces appear to be more favorable than sharp corners or sudden shape transitions. The developed framework will enable pragmatic and cost-efficient preclinical evaluation of BMHV prototypes prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design. PMID- 20571853 TI - Cylinders vs. spheres: biofluid shear thinning in driven nanoparticle transport. AB - Increasingly, the research community applies magnetophoresis to micro and nanoscale particles for drug delivery applications and the nanoscale rheological characterization of complex biological materials. Of particular interest is the design and transport of these magnetic particles through entangled polymeric fluids commonly found in biological systems. We report the magnetophoretic transport of spherical and rod-shaped particles through viscoelastic, entangled solutions using lambda-phage DNA (lambda-DNA) as a model system. In order to understand and predict the observed phenomena, we fully characterize three fundamental components: the magnetic field and field gradient, the shape and magnetic properties of the probe particles, and the macroscopic rheology of the solution. Particle velocities obtained in Newtonian solutions correspond to macroscale rheology, with forces calculated via Stokes Law. In lambda-DNA solutions, nanorod velocities are 100 times larger than predicted by measured zero-shear viscosity. These results are consistent with particles experiencing transport through a shear thinning fluid, indicating magnetically driven transport in shear thinning may be especially effective and favor narrow diameter, high aspect ratio particles. A complete framework for designing single particle magnetic-based delivery systems results when we combine a quantified magnetic system with qualified particles embedded in a characterized viscoelastic medium. PMID- 20571854 TI - Development and validation of a finite element model of the superior glenoid labrum. AB - Pathology of the superior glenoid labrum is a common source of musculoskeletal pain and disability. One of the proposed mechanisms of injury to the labrum is superior humeral head migration, which can be seen with rotator cuff insufficiency. Due to the size, anatomical location, and complex composition of the labrum, laboratory experiments have many methodological difficulties. The purpose of this study was to develop and validate a finite element model of the glenoid labrum. The model developed includes the glenoid labrum, glenoid cartilage, glenoid bone, and the humeral head cartilage. Labral displacements derived from the finite element model were compared to those measured during a controlled validation experiment simulating superior humeral head translations of 1, 2, and 3 mm. The results of the finite element model compared well to experimental measurements, falling within one standard deviation of the experimental data in most cases. The model predicted maximum average strains in the superior labrum of 7.9, 10.1, and 11.9%, for 1, 2, and 3 mm of humeral translation, respectively. The correspondence between the finite element model and the validation experiment supports the use of this model to better understand the pathomechanics of the superior labrum. PMID- 20571855 TI - Effects of low-intensity pulsed ultrasound on the expression and activity of hyaluronan synthase and hyaluronidase in IL-1beta-stimulated synovial cells. AB - The purpose of this study is to examine effects of low-intensity pulsed ultrasound (LIPUS) on metabolism of hyaluronan (HA) in synovial membrane cells stimulated by IL-1beta. Rabbit knee synovial membrane cell line, HIG-82, was cultured in medium with the presence or absence of 1 ng/mL IL-1beta, and after 4 h the cell was exposed to LIPUS for 15 min. The mRNA levels of HA synthase (HAS) 2,3, hyaluronidase (HYAL) 2, and cyclooxygenase (COX)-2 were examined by real time PCR analysis. Concentrations of HA and PGE2 were quantified by use of enzyme linked immunosorbent assay (ELISA). The COX-2 level was analyzed by western blotting. Gene levels of HAS2 and HAS3 in IL-1beta-stimulated cells were up regulated significantly (p < 0.01) by LIPUS. HYAL2 mRNA was up-regulated by the treatment with IL-1beta, whereas down-regulated significantly (p < 0.01) by the following LIPUS exposure. Furthermore, IL-1beta stimulation enhanced COX-2 and PGE2 expression as compared to the untreated control, and IL-1beta-induced COX-2 and PGE2 expression was inhibited by LIPUS. These results suggest that LIPUS enhanced HA synthesis and inhibited HYAL2 expression, leading to the accumulation of high-molecular weight HA. Therefore, LIPUS stimulation may be a better candidate as medical remedy to treat inflammatory joint diseases accompanied with HA degradation in synovial fluid. PMID- 20571856 TI - An automated segmentation approach for highlighting the histological complexity of human lung cancer. AB - Lung cancer nodules, particularly adenocarcinoma, contain a complex intermixing of cellular tissue types: incorporating cancer cells, fibroblastic stromal tissue, and inactive fibrosis. Quantitative proportions and distributions of the various tissue types may be insightful for understanding lung cancer growth, classification, and prognostic factors. However, current methods of histological assessment are qualitative and provide limited opportunity to systematically evaluate the relevance of lung nodule cellular heterogeneity. In this study we present both a manual and an automatic method for segmentation of tissue types in histological sections of resected human lung cancer nodules. A specialized staining approach incorporating immunohistochemistry with a modified Masson's Trichrome counterstain was employed to maximize color contrast in the tissue samples for automated segmentation. The developed, clustering-based, fully automated segmentation approach segments complete lung nodule cross-sectional histology slides in less than 1 min, compared to manual segmentation which requires multiple hours to complete. We found the accuracy of the automated approach to be comparable to that of the manual segmentation with the added advantages of improved time efficiency, removal of susceptibility to human error, and 100% repeatability. PMID- 20571858 TI - Clinical observed performance evaluation: a prospective study in final year students of surgery. AB - We report a prospective study of clinical observed performance evaluation (COPE) for 197 medical students in the pre-qualification year of clinical education. Psychometric quality was the main endpoint. Students were assessed in groups of 5 in 40-min patient encounters, with each student the focus of evaluation for 8 min. Each student had a series of assessments in a 25-week teaching programme. Over time, several clinicians from a pool of 16 surgical consultants and registrars evaluated each student by direct observation. A structured rating form was used for assessment data. Variance component analysis (VCA), internal consistency and inter-rater agreement were used to estimate reliability. The predictive and convergent validity of COPE in relation to summative OSCE, long case, and overall final examination was estimated. Median number of COPE assessments per student was 7. Generalisability of a mean score over 7 COPE assessments was 0.66, equal to that of an 8 * 7.5 min station final OSCE. Internal consistency was 0.88-0.97 and inter-rater agreement 0.82. Significant correlations were observed with OSCE performance (R = 0.55 disattenuated) and long case (R = 0.47 disattenuated). Convergent validity was 0.81 by VCA. Overall final examination performance was linearly related to mean COPE score with standard error 3.7%. COPE permitted efficient serial assessment of a large cohort of final year students in a real world setting. Its psychometric quality compared well with conventional assessments and with other direct observation instruments as reported in the literature. Effect on learning, and translation to clinical care, are directions for future research. PMID- 20571857 TI - MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model. AB - Rings of rat or mouse aorta embedded in collagen gels produce angiogenic outgrowths in response to the injury of the dissection procedure. Aortic outgrowths are composed of branching endothelial tubes and surrounding mural cells. Mural cells emerge following endothelial sprouting and gradually increase during the maturation of the neovessels. Treatment of aortic cultures with angiopoietin-1 (Ang-1), an angiogenic factor implicated in vascular maturation and remodeling, stimulates the mural cell recruitment process. Ang-1 induces expression of many cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1). Inhibition of p38 MAP kinase, a signaling molecule required for mural cell recruitment, blocks Ang1-induced MCP-1 expression. Recombinant MCP 1 dose-dependently increases mural cell number while an anti-MCP-1 blocking antibody reduces it. In addition, antibody mediated neutralization of MCP-1 abrogates the stimulatory effect of Ang-1 on mural cell recruitment. Aortic rings from genetically modified mice deficient in MCP-1 or its receptor CCR2 have fewer mural cells than controls. MCP-1 deficiency also impairs the mural cell recruitment activity of Ang-1. Our studies indicate that spontaneous and Ang1 induced mural cell recruitment in the aortic ring of model of angiogenesis are in part mediated by MCP-1. These results implicate MCP-1 as one of the mediators of mural cell recruitment in the aortic ring model, and suggest that chemokine pathways may contribute to the assembly of the vessel wall during the angiogenesis response to injury. PMID- 20571859 TI - The evolution of alcohol use in India. AB - This paper traces the role of alcohol production and use in the daily lives of people in India, from ancient times to the present day. Alcohol use has been an issue of great ambivalence throughout the rich and long history of the Indian subcontinent. The behaviors and attitudes about alcohol use in India are very complex, contradictory and convoluted because of the many different influences in that history. The evolution of alcohol use patterns in India can be divided into four broad historical periods (time of written records), beginning with the Vedic era (ca. 1500-700 BCE). From 700 BCE to 1100 CE, ("Reinterpretation and Synthesis") is the time of emergence of Buddhism and Jainism, with some new anti alcohol doctrines, as well as post-Vedic developments in the Hindu traditions and scholarly writing. The writings of the renowned medical practitioners, Charaka and Susruta, added new lines of thought, including arguments for "moderate alcohol use." The Period of Islamic Influence (1100-1800 CE), including the Mughal era from the 1520s to 1800, exhibited a complex interplay of widespread alcohol use, competing with the clear Quranic opposition to alcohol consumption. The fourth period (1800 to the present) includes the deep influence of British colonial rule and the recent half century of Indian independence, beginning in 1947. The contradictions and ambiguities-with widespread alcohol use in some sectors of society, including the high status caste of warriors/rulers (Kshatriyas), versus prohibitions and condemnation of alcohol use, especially for the Brahmin (scholar-priest) caste, have produced alcohol use patterns that include frequent high-risk, heavy and hazardous drinking. The recent increases in alcohol consumption in many sectors of the general Indian population, coupled with the strong evidence of the role of alcohol in the spread of HIV/STI infections and other health risks, point to the need for detailed understanding of the complex cross-currents emerging from the past history of alcohol use and abuse in India. PMID- 20571860 TI - Imagining participatory action research in collaboration with children: an introduction. PMID- 20571861 TI - Characterization of transcription within sdr region of Staphylococcus aureus. AB - Staphylococcus aureus is an opportunistic pathogen responsible for various infections in humans and animals. It causes localized and systemic infections, such as abscesses, impetigo, cellulitis, sepsis, endocarditis, bone infections, and meningitis. S. aureus virulence factors responsible for the initial contact with host cells (MSCRAMMs-microbial surface components recognizing adhesive matrix molecules) include three Sdr proteins. The presence of particular sdr genes is correlated with putative tissue specificity. The transcriptional organization of the sdr region remains unclear. We tested expression of the sdrC, sdrD, or sdrE genes in various in vitro conditions, as well as after contact with human blood. In this work, we present data suggesting a separation of the sdr region into three transcriptional units, based on their differential reactions to the environment. Differential reaction of the sdrD transcript to environmental conditions and blood suggests dissimilar functions of the sdr genes. SdrE has been previously proposed to play role in bone infections, whilst our results can indicate that sdrD plays a role in the interactions between the pathogen and human immune system, serum or specifically reacts to nutrients/other factors present in human blood. PMID- 20571862 TI - An optimized procedure for the enological selection of non-Saccharomyces starter cultures. AB - The apiculate yeasts are the species predominating the first stage of grape must alcoholic fermentation and are important for the production of desired volatile compounds. The aim of the present investigation was to establish a protocol for the enological selection of non-Saccharomyces strains directly isolated from a natural must fermentation during the tumultuous phase. At this scope, fifty Hanseniaspora uvarum isolates were characterized at strain level by employing a new combined PCR-based approach. One isolate representative of each identified strain was used in fermentation assays to assess strain-specific enological properties. The chemical analysis indicated that all the analyzed strains were low producers of acetic acid and hydrogen sulphide, whereas they showed fructophilic character and high glycerol production. Analysis of volatile compounds indicated that one strain could positively affect, during the alcoholic fermentation process, the taste and flavour of alcoholic beverages. The statistical evaluation of obtained results indicated that the selected autochthonous H. uvarum strain possessed physiological and technological properties which satisfy the criteria indicated for non-Saccharomyces wine yeasts selection. Our data suggest that the described protocol could be advantageously applied for the selection of non-Saccharomyces strains suitable for the formulation of mixed or sequential starters together with Saccharomyces cerevisiae. PMID- 20571863 TI - Associations between changing developmental contexts and risky sexual behavior in the two years following high school. AB - The present study tested associations between common developmental contexts (relationship involvement, independent living, college attendance, work) and risky sexual behavior (casual sex, inconsistent condom use, high-risk sex) across the 2 years following high school. Data were drawn from the Raising Healthy Children project, and included 801 participants aged 18-21 years. Longitudinal analyses, which controlled for early sexual debut, high school substance use, and high school grades, showed that living with a parent was protective against all three sexual risk behavior outcomes (ORs about 0.70). Being in a romantic relationship was associated with a lower probability of casual sex, but a higher probability of inconsistent condom use. Attending college was associated with a lower probability of high-risk sex (OR = 0.67). Working was not related to the sexual risk behaviors examined. Levels of sexual risk behavior showed little change across the 2 years following high school. Findings from this study suggest that developmental context may affect young adults' engagement in risky sexual behavior. Programs aimed at promoting sexual health and reducing risk behaviors for STIs among young adults should consider targeting those in romantic relationships, those not living with parents, and those not attending college. Further, to develop effective prevention programs for these targeted youth, it is critical that we understand the mechanisms leading to risky sex in these groups. PMID- 20571864 TI - Frailty, inflammation and the elderly. AB - Frailty is a term used as a marker of vulnerability, identifying individuals with a diminished capacity to respond to external stressors. Those who are frail are at increased risk of death, institutionalisation and worsening disability. While the associations of frailty with increasing chronological age, female gender, functional dependence and chronic disease are now well described, the aetiology of frailty remains less clearly understood. The growing body of evidence linking inflammation and frailty in older people, an association that seems consistent across different frailty definitions, is therefore of great interest to research gerontologists. However, further studies are needed to establish the exact nature of this relationship. Inflammation may be primarily causal, a compensatory response to viral antigens or subclinical disease or an epi-phenomenon, merely a marker of another key pathophysiological process such as excessive oxidative stress. Furthermore, it has recently been recognised that frailty is most strongly associated with a combination of immunological and physiological impairments rather than a single biomarker. This supports the conceptualisation of ageing as the progressive accumulation of damage to a complex system resulting in aggregate loss of system redundancy. The frail older person is analogous to a complex system without redundancy: capacity to respond to external stressors is reduced. A critical mass of abnormalities across different systems may therefore be a more important determinant of frailty than any individual pathway. PMID- 20571865 TI - Precise cell patterning using cytophobic self-assembled monolayer deposited on top of semi-transparent gold. AB - This paper reports a simple and effective method for cell patterning by using a self-assembled monolayer (SAM)-treated glass surface which is surrounded by semi transparent gold coated with another type of SAM. Specifically, a hydrophobic SAM, derived from 1-hexadecanethiol (HDT), was coated on the gold surface to prevent cell growth, and a hydrophilic SAM, derived from 3-trimethoxysilyl propyl diethylenetriamine (DETA), was coated on the exposed glass surface to promote cell growth. The capabilities of this technique are as follows: 1) single-cell resolution, 2) easy alignment of the cell patterns to the structures already existing on the substrate, 3) visualization and verification of the predefined cytophobic/cytophilic pattern prior to cell growth, and 4) convenient monitoring cell growth at the same location for an extended long term period of time. Whereas a number of earlier techniques have demonstrated the single cell resolution, or visualization and verification of the cytophobic/cytophilic patterns prior to cell growth, we believe that our technique is unique in possessing all of these beneficial qualities at the same time. The distinguishing characteristic of our technique is, however, that the use of semi-transparent Cr/Au film allows for convenient brightfield pattern visualization and offers an advantage over previously developed methods which require fluorescent imaging. We have successfully demonstrated the patterning of four different kinds of cells using this technique: immortalized mouse hypothalamic neurons (GT1-7), mouse osteoblast cells (MC3T3), mouse fibroblast cells (NIH3T3) and primary rat hippocampal neurons. This study was performed with a specific ultimate application-the creation of a multi electrode array (MEA) with predefined localization of cell bodies on top of the electrodes, as well as predefined patterns for cell extensions to grow in between the electrodes. With that goal in mind, we have also determined critical parameters for patterning of each of these cell types, such as the minimum size of a cell-adherent island for exclusively anchoring one cell or two cells, as well as the width of the cytophilic pathway between two islands that enables cell extensions to grow, while preventing the anchoring of the cell bodies. Additionally, we have provided statistical analysis of the occupancy for various sizes and shape of cell-anchoring islands. As demonstrated here, we have developed a novel and reliable cell patterning technique, which can be utilized in various applications, such as biosensors or tissue engineering. PMID- 20571867 TI - The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. AB - CD44+/CD24-/low tumor cells or aldehyde dehydrogenase 1 (ALDH1) positive tumor cells are considered cancer stem cells (CSCs) that possess the properties of self renewal and tumorigenicity. However, their clinical value and significance in breast cancer remain controversial. A meta-analysis based on published studies was performed with the aim of obtaining an accurate evaluation of the association between the presence of CSCs in clinical samples and clinical outcome. A total of 12 eligible studies with 898 cases and 1,853 controls were included. CSC positive breast cancers, in particular those positive for ALDH1, were significantly associated with high histological grade, estrogen receptor (ER) negativity, progesterone receptor (PR) negativity, and human epidermal growth factor receptor type 2 (HER2) positivity. However, the presence of cancer stem cells was not associated with tumor size or nodal status. ALDH1 positive (RR = 2.83, 95% CI: 2.16-3.67, P < 0.001) and CD44+/CD24-/low tumor cells (RR = 2.32, 95% CI: 1.51 3.60, P < 0.001) were significantly associated with poor overall survival (OS). The stem cell markers are prognostic factors in breast cancer. Larger clinical studies are required to further evaluate the role of these markers in clinical practice. PMID- 20571866 TI - Mitochondrial medicine: to a new era of gene therapy for mitochondrial DNA mutations. AB - Mitochondrial disorders can no longer be ignored in most medical disciplines. Such disorders include specific and widespread organ involvement, with tissue degeneration or tumor formation. Primary or secondary actors, mitochondrial dysfunctions also play a role in the aging process. Despite progresses made in identification of their molecular bases, nearly everything remains to be done as regards therapy. Research dealing with mitochondrial physiology and pathology has >20 years of history around the world. We are involved, as are many other laboratories, in the challenge of finding ways to fight these diseases. However, our main limitation is the scarcety of animal models required for both understanding the molecular mechanisms underlying the diseases and evaluating therapeutic strategies. This is especially true for diseases due to mutations in mitochondrial DNA (mtDNA), since an authentic genetic model of mtDNA mutations is technically a very difficult task due to both the inability of manipulating the mitochondrial genome of living mammalian cells and to its multicopy nature. This has led researchers in the field to consider the prospect of gene therapy approaches that can roughly be divided into three groups: (1) import of wild-type copies or relevant sections of DNA or RNA into mitochondria, (2) manipulation of mitochondrial genetic content, and (3) rescue of a defect by expression of an engineered gene product from the nucleus (allotopic or xenotropic expression). We briefly introduce these concepts and indicate where promising progress has been made in the last decade. PMID- 20571868 TI - Pharmacological interventions for fertility preservation during chemotherapy: a systematic review and meta-analysis. AB - The rate of chemotherapy-induced ovarian failure (CIOF) has been reported as 14 100% and is age- and agent-dependent. The role of GnRH analogs (GnRHa) and oral contraceptives (OC) in the prevention of CIOF is questionable. We performed a systematic review and a meta-analysis of studies assessing the efficacy of hormonal interventions in reducing CIOF in cancer or systemic lupus erythematosus (SLE) patients treated with chemotherapy. MEDLINE, EMBASE, and conference proceedings were searched until October 2009. From 504 potentially relevant references, 21 comparative studies were included for review and analysis. Data were collected to determine the risk ratio (RR) for amenorrhea, FSH levels, pregnancy rate, and biomarkers for ovarian reserve. Sixteen studies (SLE: 4 studies, 85 patients; malignancy: 12 studies, 596 patients) which assessed GnRHa for fertility preservation prior to chemotherapy were included in the meta analysis. Five studies which evaluated the use of OC were systematically reviewed. Meta-analysis revealed that GnRHa are effective in reducing amenorrhea rates in all patients (RR 0.26, 95% CI 0.14-0.49). Pregnancy rate was higher in the GnRHa arm. The advantage of GnRHa was shown only in observational studies, but not in randomized controlled trials. Biomarkers for ovarian reserve were similar in both arms. Studies evaluating the efficacy of oral contraceptives in preserving ovarian function showed inconclusive results. GnRHa appears to improve menstruation resumption. Nevertheless, randomized prospective trials are less conclusive for their real value in conserving ovarian reserve and pregnancy. Large-scale prospective randomized trials are warranted to evaluate the role of GnRHa in preventing CIOF. PMID- 20571869 TI - RAD50 gene mutations are not likely a risk factor for breast cancer in Poland. PMID- 20571870 TI - Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. AB - Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited women diagnosed as recently as 1991. The primary aim of this study was to conduct a meta-analysis that included the more recent studies. A systematic search of MEDLINE, EMBASE and CINAHL was conducted to identify original data evaluating the effects of obesity on survival in newly diagnosed breast cancer patients. Adjusted hazard ratios (HR) from individual studies were pooled using a random effects model. A series of pre-specified sensitivity analyses were conducted on factors such as overall versus breast cancer survival and treatment versus observational cohort. The meta-analysis included 43 studies that enrolled women diagnosed with breast cancer between 1963 and 2005. Sample size ranged from 100 to 424168 (median 1192). The meta-analysis showed poorer survival among obese compared with non-obese women with breast cancer, which was similar for overall (HR = 1.33; 95% confidence interval (CI): 1.21, 1.47) and breast cancer specific survival (HR = 1.33; 95% CI: 1.19, 1.50). The survival differential varied only slightly, depending on whether body mass index (1.33; 1.21, 1.47) or waist-hip ratio (1.31; 1.08, 1.58) was used as the measure of obesity. There were larger differences by whether the woman was pre-menopausal (1.47) or post-menopausal (1.22); whether the cohort included women diagnosed before (1.31) or after 1995 (1.49); or whether the women were in a treatment (1.22) or observational cohort (1.36), but none of the differences were statistically significant. Women with breast cancer, who are obese, have poorer survival than women with breast cancer, who are not obese. However, no study has elucidated the causal mechanism and there is currently no evidence that weight loss after diagnosis improves survival. Consequently, there is currently no reason to place the additional burden of weight loss on women already burdened with a diagnosis of cancer. Further research should concentrate on assessing whether factors such as diabetes or type of chemotherapy modify the obesity effect and on understanding the causal mechanism, in particular the role of relative under-dosing. PMID- 20571871 TI - Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival. AB - INTRODUCTION: Breast cancer (BrCA) risk stratification using clinico-pathological biomarkers helps improve disease prognosis prediction. However, disease recurrence rates remain unfavorable and individualized clinical management strategies are needed. Consequently, we evaluated the influence of 14 sequence variants detected in IL-10, TGF-beta1, VEGF, and their associated receptors as effective predictors of BrCA clinical outcomes. METHODS: Tumor DNA samples collected from 441 BrCA patients were genotyped using TaqMan-PCR. Most selected targets alter cytokine serum/plasma levels or signaling pathways. Relationships between genetic profiles and recurrence as well as disease-related mortality were evaluated using cumulative incidence curves and competing risk regression models. RESULTS: The VEGF(-2578)C allele was associated with a 1.3- to 1.6-fold increase in BrCA recurrence (HR(trend) = 1.28; 95% CI = 0.96-1.72) and disease-related mortality (HR(trend) = 1.56; 95% CI = 0.93-2.56). Although this marker was marginally significant relative to BrCA outcomes, there were substantial gains in the 5- and 8-year predictive accuracy compared to standard prognostic indicators. Among ER(+)/PR(+) status patients, there was a significant impact of the VEGF( 2578)CC genotype on disease recurrence and predictive accuracy. CONCLUSIONS: Our findings suggest inheritance of the VEGF(-2578)C allele could serve as an independent prognostic indicator of BrCA prognosis. The VEGF(-2578) marker may have clinical implications among a subset of ER(+)/PR(+) patients with an aggressive phenotype. Because the VEGF(-2578)C allele is linked to high VEGF expression, this cytokine is a potential prognostic and targeted clinical management tool. PMID- 20571872 TI - Cardiac magnetic resonance imaging; gatekeeper in suspected CAD? PMID- 20571873 TI - Left atrial flow propagation velocity: a new approach for assessment of left atrial reservoir function. AB - To assess the feasibility of left atrial flow propagation velocity (LAFPV) measurement and to evaluate the influence of preload alterations on this new parameter of left atrial (LA) reservoir function as compared to conventional echocardiographic indices. 30 healthy volunteers (26 +/- 5 years, 20 males) underwent echocardiographic examination at rest, during passive leg lifting and after sublingual administration of nitroglycerine with subsequent Valsalva maneuver. LA reservoir function was assessed by conventional indices including LA expansion index, peak velocity and velocity-time integral of pulmonary venous systolic flow. As well, LAFPV was measured by color M-mode in an apical 4-chamber view as the slope of the transatrial flow wave during LA reservoir phase. LAFPV measurement was feasible in 25 subjects (83%). All conventional parameters of LA reservoir function were significantly altered from resting values by both load modifying conditions. However, LAPFV was not significantly altered by such maneuvers (228 +/- 28 cm s-1 at rest vs. 238 +/- 3 cm s-1 during leg lifting, P = NS, vs. 218 +/- 38 cm s(-1) after nitroglycerin with Valsalva maneuver, P = NS vs. rest, P < 0.01 vs. leg lifting). LAFPV can be measured in a majority of subjects and represents a new, less load-dependent index of LA reservoir function that may more appropriately reflect LA compliance. PMID- 20571874 TI - Contraindications and side effects of commonly used medications in coronary CT angiography. AB - For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the beta blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies. PMID- 20571875 TI - Human tyrosine hydroxylase natural allelic variation: influence on autonomic function and hypertension. AB - The catecholamine biosynthetic pathway consists of several enzymatic steps in series, beginning with the amino acids phenylalanine and tyrosine, and eventuating in the catecholamines norepinephrine (noradrenaline) and epinephrine (adrenaline). Since the enzyme tyrosine hydroxylase (TH; tyrosine 3-mono oxygenase; EC 1.14.16.2; chromosome 11p15.5) is generally considered to be rate limiting in this pathway, probed as to whether common genetic variation at the TH gene occurred, and whether such variants contributed to inter-individual alterations in autonomic function, either biochemical or physiological. We began with sequencing a tetranucleotide (TCAT) repeat in the first intron, and found that the two most common versions, (TCAT)(6) and (TCAT)(10i), predicted heritable autonomic traits in twin pairs. We then conducted systematic polymorphism discovery across the ~8 kbp locus, and discovered numerous variants, principally non-coding. The proximal promoter block contained four common variants, and its haplotypes and SNPs (especially C-824T, rs10770141) predicted catecholamine secretion, environmental stress-induced BP increments, and hypertension. Finally, we found that two of the common promoter variants, C-824T (rs10770141) and A-581G (rs10770140), were functional in that they differentially affected transcriptional activity of the isolated promoter, disrupted recognition motifs for specific transcription factor binding, altered the promoter responses to the co-transfected (exogenous) factors, and bound the endogenous factors in the chromatin fraction of the nucleus. We concluded that common variation in the proximal TH promoter is functional, giving rise to changes in autonomic function and consequently cardiovascular risk. PMID- 20571876 TI - Genome structure affects the rate of autosyndesis and allosyndesis in AABC, BBAC and CCAB Brassica interspecific hybrids. AB - Gene introgression into allopolyploid crop species from diploid or polyploid ancestors can be accomplished through homologous or homoeologous chromosome pairing during meiosis. We produced trigenomic Brassica interspecific hybrids (genome complements AABC, BBAC and CCAB) from the amphidiploid species Brassica napus (AACC), Brassica juncea (AABB) and Brassica carinata (BBCC) in order to test whether the structure of each genome affects frequencies of homologous and homoeologous (both allosyndetic and autosyndetic) pairing during meiosis. AABC hybrids produced from three genotypes of B. napus were included to assess the genetic control of homoeologous pairing. Multi-colour fluorescent in situ hybridisation was used to quantify homologous pairing (e.g. A-genome bivalents in AABC), allosyndetic associations (e.g. B-C in AABC) and autosyndetic associations (e.g. B-B in AABC) at meiosis. A high percentage of homologous chromosomes formed pairs (97.5-99.3%), although many pairs were also involved in autosyndetic and allosyndetic associations. Allosyndesis was observed most frequently as A-C genome associations (mean 4.0 per cell) and less frequently as A-B genome associations (0.8 per cell) and B-C genome associations (0.3 per cell). Autosyndesis occurred most frequently in the haploid A genome (0.75 A-A per cell) and least frequently in the haploid B genome (0.13 B-B per cell). The frequency of C-C autosyndesis was greater in BBAC hybrids (0.75 per cell) than in any other hybrid. The frequency of A-B, A-C and B-C allosyndesis was affected by the genomic structure of the trigenomic hybrids. Frequency of allosyndesis was also influenced by the genotype of the B. napus paternal parent for the three AABC (B. juncea * B. napus) hybrid types. Homoeologous pairing between the Brassica A, B and C genomes in interspecific hybrids may be influenced by complex interactions between genome structure and allelic composition. PMID- 20571877 TI - Developing a framework to support shared decision making for youth mental health medication treatment. AB - Medical shared decision making has demonstrated success in increasing collaboration between clients and practitioners for various health decisions. As the importance of a shared decision making approach becomes increasingly valued in the adult mental health arena, transfer of these ideals to youth and families of youth in the mental health system is a logical next step. A review of the literature and preliminary, formative feedback from families and staff at a Midwestern urban community mental health center guided the development of a framework for youth shared decision making. The framework includes three functional areas (1) setting the stage for youth shared decision making, (2) facilitating youth shared decision making, and (3) supporting youth shared decision making. While still in the formative stages, the value of a specific framework for a youth model in support of moving from a client-practitioner value system to a systematic, intentional process is evident. PMID- 20571878 TI - Anti-invasion, anti-proliferation and anoikis-sensitization activities of lapatinib in nasopharyngeal carcinoma cells. AB - Nasopharyngeal cancer (NPC) is a highly prevalent and invasive head and neck cancer in Asia. Disease recurrence and distant metastasis account for major NPC deaths. Therefore, more effective therapy is needed. Lapatinib, a dual tyrosine kinase inhibitor (TKI) against both EGFR and HER-2, has been known to exert potent antitumor activity against several cancer models. Given that both EGFR and HER-2 are co-expressed in NPC, we hypothesized that dual targeting of EGFR and HER-2 by this small molecule EGFR/HER-2 TKI would elicit anti-tumor activity in NPC. Using in vitro models of NPC, we demonstrated that lapatinib was able to efficiently inhibit the phosphorylation of both EGFR and HER-2. This was accompanied by significant growth inhibition of NPC cells (with maximal growth inhibition >90%). For the most lapatinib-sensitive cell line (HK1-LMP1, with IC(50) ~ 600 nM), which harbored the highest levels of both EGFR and HER-2, inhibition of cell growth was associated G(0)/G(1) cell cycle arrest, marked PARP cleavage, caspase-3 cleavage, as well as significant downregulation of several important survival proteins (e.g. survivin, Mcl-1 and cyclin D1). NPC cells are intrinsically invasive. We found that lapatinib was able to inhibit cellular invasion of both HK1-LMP1 and HONE-1 cells. Furthermore, our data demonstrated for the first time that lapatinib harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced apoptosis) in human cancer cells overexpressing both EGFR and HER-2 (HK1-LMP1 and HK1). Taken together, our findings suggest that lapatinib is a promising anti-cancer agent for NPC with anti-invasion and anoikis-sensitization activities. PMID- 20571879 TI - Mercury-induced oxidative stress and impact on antioxidant enzymes in Chlamydomonas reinhardtii. AB - Investigation of mercury toxicology in green algae is of great importance from ecological point of view, because mercury has become a major contaminant in recent years. In higher plants, accumulation of mercury modifies many aspects of cellular functions. However, the process that mercury exerts detrimental effects on green algae is largely unknown. In this study, we performed an experiment focusing on the biological responses of Chlamydomonas reinhardtii, a unicellular model organism, to Hg(2+)-induced toxicity. C. reinhardtii was exposed to 0, 1, 2, 4, 6, and 8 MUM Hg in media. Concentrations of Hg were negatively correlated with the cell growth. Treatment with Hg induced accumulation of reactive oxygen species and peroxidative products. Endogenous proline levels increased in Hg exposed algae. Hg exposure activated superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). To get insights into the molecular response, a RT PCR-based assay was performed to analyze the transcript abundance of Mn-SOD, CAT and APX. Our analysis revealed that expression of the genes was up-regulated by Hg exposure, with a pattern similar to the enzyme activities. Additional investigation was undertaken on the effect of Hg on the transcript amount of ?(1) pyrroline-5-carboxylate synthetase, a key enzyme of proline biosynthesis and on that of heme oxygenase-1 (HO-1), an enzyme regulating heavy metal tolerance. Expressions of both P5CS and HO-1 were up-regulated by Hg. These data indicate that Hg-induced oxidative stress was responsible for the disturbance of the growth and antioxidant defensive systems in C. reinhardtii. PMID- 20571880 TI - Utilization and effectiveness of medical rehabilitation in foreign nationals residing in Germany. AB - In Germany, the proportion of foreign national residents receiving an invalidity pension is higher than that of Germans. Lower utilization and effectiveness of medical rehabilitation are presumed to be the main reasons. We aimed to examine whether differences in utilization and effectiveness of medical rehabilitation between Germans and foreign nationals are attributable to differences in socio demography, socio-economic background and health status. Utilization of rehabilitation was analyzed for household members aged 18 years or above enrolled in the German Socio-Economic Panel in 2002-2004 (n = 19,521). Effectiveness of rehabilitation was defined by the occupational performance at the end of rehabilitation. It was examined by using an 80% random sample of all completed medical rehabilitations in the year 2006 funded by the German Statutory Pension Insurance Scheme (n = 634,529). Our study shows that foreign nationals utilize medical rehabilitation less often than Germans (OR = 0.68; 95%-CI = 0.50; 0.91). For those who do, medical rehabilitation is less effective (OR for low occupational performance = 1.50; 95%-CI = 1.46; 1.55). Both findings are only partially attributable to socio-demographic, socio-economic and health characteristics: After adjusting for these factors, ORs for utilization and low occupational performance were 0.66 (95%-CI = 0.49; 0.90) and 1.20 (95%-CI = 1.16; 1.24), respectively. It can be concluded that differences in the utilization and effectiveness of medical rehabilitation between Germans and foreign nationals cannot be explained only by socio-economic differences or poorer health before rehabilitation. In addition, factors such as the ability of the rehabilitative care system to accommodate clients with differing expectations, and migrant specific characteristics such as cultural differences, seem to play a role. PMID- 20571881 TI - Little Egret (Egretta garzetta) as a bioindicator of trace element pollution in Tunisian aquatic ecosystems. AB - The Little Egret, Egretta garzetta, has breeding colonies in the island of Chikly (in the lake of Tunis) and in Thyna saltpans (in the gulf of Gabes), two important Tunisian wetlands that are strongly affected by anthropogenic activity. Here, we used E. garzetta chick feathers for environmental monitoring of breeding grounds of this species. Since trophic ecology is fundamental when interpreting contamination levels, our approach combined both trace-element (Hg, Pb, Cd, and Se) and stable-isotope analysis of delta13C, delta15N, and delta34S. Hg, Se, and delta15N levels were higher in specimens collected on Chikly than in Thyna. These observations highlight the degree of eutrophication of the lake of Tunis. Yellow legged gulls (Larus michahellis) breeding in the same areas also feeds in the lake and attains similar concentrations of Hg and Se. In Thyna, egrets and gulls exploit distinct foraging habitats, as demonstrated by stable isotope analysis. The highest Hg and Se concentrations were found in Thyna. This result is consistent with greater exploitation of marine resources from the gulf of Gabes. PMID- 20571882 TI - Examination of the operator and compensator tank role in urban wastewater treatment using activated sludge method. AB - No doubt, operator is one of the main fundaments in wastewater treatment plants. By identifying the inadequacies, the operator could be considered as an important key in treatment plant. Several methods are used for wastewater treatment that requires spending a lot of cost. However, all investments of treatment facilities are usable when the expected efficiency of the treatment plant was obtained. Using experienced operator, this goal is more easily accessible. In this research, the wastewater of an urban community contaminated with moderated, diluted and highly concentrated pollution has been treated using surface and deep aeration treatment method. Sampling of these pilots was performed during winter 2008 to summer 2009. The results indicate that all analyzed parameters were eliminated using activated sludge and surface aeration methods. However, in activated sludge and deep aeration methods in combination with suitable function of operator, more pollutants could be eliminated. Hence, existence of operator in wastewater treatment plants is the basic principle to achieve considered efficiency. Wastewater treatment system is not intelligent itself and that is the operator who can organize even an inefficient system by its continuous presence. The converse of this fact is also real. Despite the various units and appropriate design of wastewater treatment plant, without an operator, the studied process cannot be expected highly efficient. In places frequently affected by the shock of organic and hydraulic loads, the compensator tank is important to offset the wastewater treatment process. Finally, in regard to microbial parameters, existence of disinfection unit is very useful. PMID- 20571883 TI - Tissue distribution of 210Po and 210Pb in select marine species of the coast of Kudankulam, southern coast of Gulf of Mannar, India. AB - Activities of 210Po and 210Pb in various tissues of four species of decapod crabs and two species of cephalopod mollusks (cuttlefishes) of Kudankulam coast were studied. A non-uniform distribution of these radionuclides was observed between the organs. Of all the tissues, 210Po and 210Pb were found accumulated more in the hepatopancreas and intestine of crabs and in the digestive gland, shell gland, and intestine of cephalopods. Among crabs, Charybdis lucifera registered a little higher 210Po and 210Pb activities. The cephalopod species Loligo duvauceli displayed higher 210Po and 210Pb in some organs when compared to Sepia pharaonis. The muscle of all the species registered lower activity. In cephalopods, the activity ratio of 210Po/210Pb fell within the range of 1-2 for most of the organs, and in crab tissues, it varied from 1.7 to 31.4. The biological concentration factor for organs of cephalopods ranged from 1.2*10(3) to 4.3*10(5) for 210Po and 4.8*10(2) to 8.4*10(4) for 210Pb and for organs of crabs it varied between 2.0*10(4) and 1.9*10(6) for 210Po and 9.2*10(2) and 2.4*10(4) for 210Pb. The study revealed that the organs associated with digestion and metabolism displayed a higher activity concentration than the other tissues. A significant variation in the accumulation of 210Po and 210Pb was noted between species (P<0.05). The activity levels recorded are in agreement with values recorded in related organisms in other parts of the world. The data generated will act as a reference database for these organisms of this coast in which a nuclear power station is under construction. PMID- 20571884 TI - Lichen transplants as a suitable tool to identify mercury pollution from waste incinerators: a case study from NE Italy. AB - A lichen transplant study aimed at investigating a strong increase in mercury concentrations in lichens was run in a territory of NE Italy where background values were very low only 8 years before. Thalli of the lichen Pseudevernia furfuracea collected in a pristine area were exposed for 1.5, 3 and 6 months at 31 sites selected according to the observed pattern of Hg concentrations, location of the suspected source (a new waste incinerator) and prevailing wind direction. Hg strongly increased at eight sites after 1.5 months, at 12 after 3 months and at 20 after 6 months. The highest values were always located SW and S of the incinerator, in good agreement with the prevailing night wind direction. It was concluded that, although the immediate risk for the population living close to the incinerator is low, long-term hazard due to Hg accumulation in the surrounding environment should be seriously taken into account. PMID- 20571885 TI - Using hybrid method to evaluate the green performance in uncertainty. AB - Green performance measure is vital for enterprises in making continuous improvements to maintain sustainable competitive advantages. Evaluation of green performance, however, is a challenging task due to the dependence complexity of the aspects, criteria, and the linguistic vagueness of some qualitative information and quantitative data together. To deal with this issue, this study proposes a novel approach to evaluate the dependence aspects and criteria of firm's green performance. The rationale of the proposed approach, namely green network balanced scorecard, is using balanced scorecard to combine fuzzy set theory with analytical network process (ANP) and importance-performance analysis (IPA) methods, wherein fuzzy set theory accounts for the linguistic vagueness of qualitative criteria and ANP converts the relations among the dependence aspects and criteria into an intelligible structural modeling used IPA. For the empirical case study, four dependence aspects and 34 green performance criteria for PCB firms in Taiwan were evaluated. The managerial implications are discussed. PMID- 20571886 TI - Peutz-Jeghers syndrome: a study of long-term surgical morbidity and causes of mortality. AB - Patients with Peutz-Jeghers syndrome (PJS) require lifelong multidisciplinary care for gastrointestinal polyposis and increased risk of cancer. Their long-term morbidities and causes of mortality are unknown. Patients with a definitive diagnosis of PJS (n = 54) were retrospectively reviewed for disease course and outcome. Operative details, pathology and complications were noted for those treated surgically (n = 33). Median follow-up was 7.0 years (interquartile range: 2-20). Two malignancies were found intra-operatively (duodenal and rectal adenocarcinoma). In the long-term, 42% underwent additional operations; 1 patient developed short bowel syndrome, while another, chronic partial bowel obstruction and pain. Twenty-one additional cancers were treated in 19 patients: gynecologic (11), lung (3), and prostate (2) being the most common. 16 patients (30%) were deceased, at a median age of 51 years. The cause of death was unknown in 4 patients, but was due exclusively to malignancies in all other patients, most commonly due to metastatic gynecologic cancer (5). The overall survival of PJS patients was significantly shorter than the expected survival of an age-and gender-matched reference population (P < 0.001). Given the morbidities associated with repeated operations and the risk for cancer-related mortality in the long term, efforts should focus on minimizing the need for surgical intervention and optimizing cancer detection, treatment and prevention. PMID- 20571887 TI - Intracellular localization of GASP/ECOP/VOPP1. AB - Vesicular Over-expressed in cancer Prosurvival Protein 1 (VOPP1), also known as Glioblastoma Amplified and Secreted Protein and EGFR-Coamplified and Over expressed Protein has been previously shown to be over-expressed in human glioblastoma multiforme and squamous cell carcinoma. Additionally, previous experimental work suggests that it confers a prosurvival cellular phenotype. A query of a public database of gene expression profiling data (Oncomine) shows that the VOPP1 transcript is also highly expressed in several other common human cancers, including breast carcinoma, pancreatic carcinoma, and lymphoma. Analysis of VOPP1 sequence structure shows both a signal sequence and a transmembrane domain, and examination of a public microarray dataset for endoplasmic reticulum (ER)-bound mRNA transcripts is consistent with the VOPP1 protein product being synthesized into the ER. Immunoblot analysis of cell culture and conditioned media confirms that the protein product is not secreted and is retained intracellularly. VOPP1 protein tagged with a fluorescence reporter, as well as antibody-mediated visualization of recombinant and native forms of the protein reveals an intracellular vesicular pattern of localization. Co-localization experiments reveal that VOPP1 vesicles do not co-localize with mitochondria or peroxisomes, but show partial co-localization with perinuclear lysosomes. Additionally, markers of endocytosis and autophagy show partial perinuclear co localization, suggesting that VOPP1-containing vesicles enter final common pathways of the lysosomal system. These findings throw into doubt the hypothesis that VOPP1 interacts directly with cytoplasmic mediators of the NF kappa B pathway, and suggest that the prosurvival phenotype conferred by this gene product is mediated by other mechanisms. PMID- 20571889 TI - Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms. AB - Cardiac dysfunction is a well-recognized complication of severe sepsis and septic shock. Cardiac dysfunction in sepsis is characterized by ventricular dilatation, reduction in ejection fraction and reduced contractility. Initially, cardiac dysfunction was considered to occur only during the "hypodynamic" phase of shock. But we now know that it occurs very early in sepsis even during the "hyperdynamic" phase of septic shock. Circulating blood-borne factors were suspected to be involved in the evolution of sepsis induced cardiomyopathy, but it is not until recently that the cellular and molecular events are being targeted by researchers in a quest to understand this enigmatic process. Septic cardiomyopathy has been the subject of investigation for nearly half a century now and yet controversies exist in understanding it's pathophysiology. Here, we discuss our understanding of the pathogenesis of septic cardiomyopathy and the complex roles played by nitric oxide, mitochondrial dysfunction, complements and cytokines. PMID- 20571890 TI - Case report: Goldenhar syndrome following donor oocyte IVF. AB - PURPOSE: To describe a case of Goldenhar syndrome in a couple receiving donated oocytes in an 'egg sharing' IVF cycle where the recipient of donor oocytes had Turner syndrome, hypothyroidism and gestational diabetes. METHODS: Case report RESULTS: Child born to oocyte recipient with Goldenhar syndrome CONCLUSIONS: We believe this is the first reported case of a child born with Goldenhar syndrome following use of donated oocytes in IVF by a woman with Turner syndrome, hypothyroidism and gestational diabetes. PMID- 20571891 TI - Crystal and solution structure of the C-terminal part of the Methanocaldococcus jannaschii A1AO ATP synthase subunit E revealed by X-ray diffraction and small angle X-ray scattering. AB - The structure of the C-terminus of subunit E (E(101-206)) of Methanocaldococcus jannaschii A-ATP synthase was determined at 4.1 A. E(101-206) consist of a N terminal globular domain with three alpha-helices and four antiparallel beta strands and an alpha-helix at the very C-terminus. Comparison of M. jannaschii E(101-206) with the C-terminus E(81-198) subunit E from Pyrococcus horikoshii OT3 revealed that the kink in the C-terminal alpha-helix of E(81-198), involved in dimer formation, is absent in M. jannaschii E(101-206). Whereas a major dimeric surface interface is present between the P. horikoshii E(81-198) molecules in the asymmetric unit, no such interaction could be found in the M. jannaschii E(101 206) molecules. To verify the oligomeric behaviour, the low resolution structure of the recombinant E(85-206) from M. jannaschii was determined using small angle X-ray scattering. Rigid body modeling of two copies of one of the monomer established a fit with a tail to tail arrangement. PMID- 20571892 TI - "There is no proof that HIV causes AIDS": AIDS denialism beliefs among people living with HIV/AIDS. AB - AIDS denialists offer false hope to people living with HIV/AIDS by claiming that HIV is harmless and that AIDS can be cured with natural remedies. The current study examined the prevalence of AIDS denialism beliefs and their association to health-related outcomes among people living with HIV/AIDS. Confidential surveys and unannounced pill counts were collected from a convenience sample of 266 men and 77 women living with HIV/AIDS that was predominantly middle-aged and African American. One in five participants stated that there is no proof that HIV causes AIDS and that HIV treatments do more harm than good. AIDS denialism beliefs were more often endorsed by people who more frequently used the internet after controlling for confounds. Believing that there is a debate among scientists about whether HIV causes AIDS was related to refusing HIV treatments and poorer health outcomes. AIDS denialism beliefs may be common among people living with HIV/AIDS and such beliefs are associated with poor health outcomes. PMID- 20571893 TI - Selective IgA deficiency in children in Israel. AB - IgA deficiency is the most common human primary immune-deficiency. We evaluated the clinical and immunological characteristics of selective IgA deficiency in children in Israel. The study group included 63 children diagnosed with IgA deficiency from 1987 to 2005. Mean follow-up time per child was 10.6 years. Average age at diagnosis was 10.5 years. In one child, the IgA deficiency was transient. Infectious diseases, mainly recurrent pneumonia and ear infection, were common and occurred in 25 patients (39.7%). Allergic diseases were documented in 20 (31.7%) of our patients. Thirteen children (20.6%) had autoimmune diseases. Malignancies were diagnosed in three children (4.8%), an association that has not been reported in previous series. IgA deficiency appears to be a risk factor for infections, allergic diseases, autoimmune conditions, and malignancy. PMID- 20571888 TI - TNFalpha in myocardial ischemia/reperfusion, remodeling and heart failure. AB - TNFalpha is crucially involved in the pathogenesis and progression of myocardial ischemia/reperfusion injury and heart failure. The formation and release of TNFalpha and its downstream signal transduction cascade following activation of its two receptor subtypes are characterized. Myocardial TNFalpha and TNF receptor activation have an ambivalent role in myocardial ischemia/reperfusion injury and protection from it. Excessive TNFalpha expression and subsequent cardiomyocyte TNF receptor type 1 stimulation induce contractile dysfunction, hypertrophy, fibrosis and cell death, while a lower TNFalpha concentration and subsequent cardiomyocyte TNF receptor type 2 stimulation are protective. Apart from its concentration and receptor subtype, the myocardial action of TNFalpha depends on the duration of its exposure and its localization. While detrimental during sustained ischemia, TNFalpha contributes to ischemic preconditioning protection, no matter whether it is the first, second or third window of protection, and both TNF receptors are involved in the protective signal transduction cascade. Finally, the available clinical attempts to antagonize TNFalpha in cardiovascular disease, notably heart failure, are critically discussed. PMID- 20571894 TI - IL-2 immunotherapy to recently HIV-1 infected adults maintains the numbers of IL 17 expressing CD4+ T (T(H)17) cells in the periphery. AB - Little is known about the manipulation of IL-17 producing CD4+ T cells (T(H)17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of T(H)17 cells declined, while counts of T(H)17 cells did not change due to an expansion of the CD4+ naive T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of T(H)17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV 1 Gag. PMID- 20571895 TI - The NBS1 genetic polymorphisms and the risk of the systemic lupus erythematosus in Taiwanese patients. AB - INTRODUCTION: Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is characterized by the production of a range of autoantibodies against nuclear constituents and other self-antigens. The studies in DNA repair deficiencies in SLE patients have been recently investigated. AIMS: Few studies have been conducted on DNA repair gene polymorphisms and their role in autoimmune diseases. Our study purpose was to examine and compare NBS1 genotype distributions in a group of Taiwanese SLE patients and controls in Taiwan. PATIENTS AND METHODS: Participants were Taiwanese SLE patients and healthy controls. We studied associations among NBS1 polymorphisms--rs1061302, rs709816, and rs1805794--considering clinical features for the entire group and stratified subgroups. No statistically significant differences between the patients and controls were noted. However, we observed significant decreases in Ht1-GGG, Ht2 AAC, and Ht3-AGC in the SLE patients (Ht1-GGG, OR = 0.26, 95% CI: 0.16-0.41; Ht2 AAC, OR = 0.30, 95% CI: 0.17-0.53; Ht3-AGC, OR = 0.35, 95% CI: 0.19-0.71) and significant increases in Ht4-AAG, Ht5-AGG, and Ht8-GGC among the SLE patients. Combined, these results suggest an association between NBS1 genetic polymorphisms and Taiwanese SLE patients. PMID- 20571896 TI - Sex pheromone of the Spanish population of the beet armyworm Spodoptera exigua. AB - The pheromone composition of the Spanish population of the beet armyworm (BAW), Spodoptera exigua (Lepidoptera: Noctuidae), was identified. Analysis of female gland extracts showed the presence of compounds Z9,E12-14:Ac (1), Z9-14:Ac (2), Z11-16:Ac (3), Z9,E12-14:OH (4), Z9-14:OH (5), and Z11-16:OH (6) in a ratio of 26:11:1:22:31:9. The amount of compound per gland ranged from 2.08 ng for 5 to 0.09 ng for 3. However, analysis of female volatiles by SPME revealed only the presence of compounds, 1, 2, 3, and 5 in a 34:40:4:22 ratio. In electroantennogram assays, compound 1 elicited the highest response, and the C14 acetates evoked higher electrophysiological responses than the corresponding alcohols or C16 isomers. In a wind tunnel, no behavioral difference was observed between formulations based on the gland extracts and female volatiles. In both cases, males responded as when virgin females were used as the attractant source. Compound 1 alone elicited upwind flight by males, but required the presence of compound 5 in a 80:20 to 40:60 ratio for full activity. Ternary mixtures of 1, 5 and the minor components did not improve the performance of the 1+5 blend in a 60:40 ratio. In the field, the mixture 1+5+3 in a 56:37:7 ratio was the most attractive formulation, and is expected to be useful in future pest control strategies. PMID- 20571897 TI - High prevalence of affective disorders among adolescents living in Rural Zimbabwe. AB - Poor mental health accounts for considerable disease burden among young people globally. We investigated the prevalence and determinants of affective disorders among rural Zimbabwean youth in 2006. We undertook a cross-sectional survey among 1495 Zimbabwean youth aged 15-23 (median 18) from 12 rural communities in three provinces in south-eastern Zimbabwe. Mental health was assessed using the Shona Symptom Questionnaire (SSQ), a locally validated 14-item indigenous screening tool for affective disorders, notably depression and anxiety disorders. Participants scoring >or=8/14 were considered at risk of being affected and >or=11 as at risk of being severely affected. Most participants (93.1%) completed the SSQ. Of these, 51.7% (95%CI:49.0-54.3%) scored >or=8/14 and 23.8% (95%CI:21.5 26.0%) scored >or=11. Affective disorders were independently associated with household poverty (adjusted odds ratio (AOR) 1.9, 95%CI:1.4-2.7), living in a female-headed household (AOR 1.3, 95%CI:1.0-1.7), having moved home within last 5 years (AOR 1.4, 95%CI:1.0-1.9) and feeling stigmatized (AOR being shunned by others 3.7, 95%CI:2.5-5.7). There was a strong linear association between risk of affective disorders and sexual risk taking (ever sex AOR 1.5, 95%CI:1.0-2.4, and 2.8, 95%CI:1.9-4.2 for affected and severely affected, respectively, test for trend P < 0.001; >or=2 lifetime partners AOR 2.3, 95%CI:1.1-4.8 and 5.4, 95%CI:2.7-10.7, test for trend P < 0.001). This study indicates high levels of psychological morbidity among rural Zimbabwean youth which was associated with sexual risk taking. Interventions to prevent, identify and treat mental health disorders in this vulnerable population are urgently required. In HIV-endemic countries, such interventions may also help reduce HIV transmission. PMID- 20571898 TI - Cervical cancer screening among Southeast Asian American women. AB - The incidence of cervical cancer is high among Southeast Asian American women, but their participation in preventive cervical cancer screening is alarmingly low. This paper reviews the literature on factors associated with participation in cervical cancer screening among women of Vietnamese, Cambodian and Hmong descent in the United States. These factors include acculturation, age, marital status, knowledge about cervical cancer, apprehension about cervical cancer screening, financial concerns, access to health care, and physician characteristics and recommendation. Suggestions for future research include the need to investigate the role of physicians treating Southeast Asian American women, the need for more extensive up-to-date studies on the current generation of young Southeast Asian American women, and the use of more advanced assessments of acculturation. Overall, much more work is needed in order to deepen our understanding of the various ways to improve the rate of cervical cancer screening among Southeast Asian American women. PMID- 20571899 TI - Inhibition of botulinum neurotoxin a toxic action in vivo by synthetic synaptosome- and blocking antibody-binding regions. AB - In previous studies, we showed that certain peptides of the H(N) and H(C) domains of the H-chain of BoNT/A bind to mouse brain synaptosomes (snps). There was either complete correspondence or overlap between peptides that bind snps and those that bind human or mouse blocking antibodies (Abs). An equimolar mixture of the overlapping peptides N5/N6/N7/N8 (residues 505-523/519-537/533-551/547-565) extended the survival time of the mice to 74 h (20%) relative to controls, which had a 50% survival time of 60 h. On the other hand, peptide N26 (residues 799 817) provided no protection (50% survival time, 58 h), but the overlapping peptide N25 (785-803) almost doubled the 50% survival time to 119 h. A mixture of the overlap N25/N26 provided an unexpected level of protection permitting 40% of the mice to survive a lethal BoNT/A dose. In the H(C) domain, the overlap C23/C24 (1163-1181/1177-1195) provided no protection. Peptide C31 (1275-1296) also provided no significant protection. But an equimolar mixture of peptides C15/C16 (1051-1069/1065-1083) or peptides C18/C19/C20 (1093-1111/1107-1125/1121-1139) extended the 50% survival time by 41% (to 85 h) over controls (60 h) and was able to fully protect 20% of the mice which eventually recovered. Surprisingly, the mixture of the peptides C15/C16 and C18/C19/C20, which gave a 50% survival time of 75 h, was less protective than either peptides C15/C16 or peptides C18/C19/C20. The in vivo inhibitory activity of these peptides is discussed in relation to their location in the 3-dimensional structure of the toxin molecule and their membrane receptor binding. PMID- 20571900 TI - Latino adolescents' loneliness, academic performance, and the buffering nature of friendships. AB - This longitudinal study examined Latino adolescents' feelings of loneliness and the repercussions of loneliness for later educational success. Participants were 640 Latino students (56% girls, 62% Mexican/Mexican-American) who reported on loneliness across the first 2 years of high school. Growth mixture modeling identified three distinct loneliness trajectory classes for the Latino adolescents--consistently low, chronically high, and low but increasing. Language brokering, language use, and school mobility emerged as predictors of class membership. Increasingly and chronically lonely youth experienced academic difficulty, both in terms of academic progress and exit exam success, but support from friends served as a buffer of the negative relationship between loneliness and academic success. This study highlights the pernicious effects of loneliness and suggests promoting prosocial friendship support as a means of facilitating more positive academic outcomes for Latino youth. PMID- 20571901 TI - A comparison between Swedish midwives' and obstetricians' & gynecologists' opinions on cesarean section. AB - To compare Swedish obstetricians/gynecologists and midwives' attitudes and opinions on different aspects of cesarean section (CS). In total 330 midwives from the south east of Sweden and 1280 Swedish obstetricians/gynecologists were asked to answer a study-specific questionnaire anonymously about their opinions on different issues concerning CS. The majority of obstetricians/gynecologists and midwives had more than 10 years of experience in their professions (75.2% vs. 73.6%). The midwives thought that a reasonable CS rate would be 11.5% whereas the corresponding figures for the obstetricians/gynecologists was 13.8% (P < 0.001). There are differences in opinions and attitudes concerning both CS rates and other aspects in connection with CS. There are evident differences in attitudes towards CS and mode of delivery between midwives and obstetricians/gynecologists. These need to be explored and discussed in relation to state-of-the-art knowledge and should become a part of the curriculum for both groups of professionals both in training as well as on a regular clinical basis. PMID- 20571902 TI - An examination of maternity staff attitudes towards implementing Baby Friendly Health Initiative (BFHI) accreditation in Australia. AB - BACKGROUND: The Baby Friendly Hospital Initiative (BFHI) influences health care practices and increases the initiation and duration of exclusive breastfeeding. Consistent definitions enable the accurate monitoring of breastfeeding rates and behaviour. This information refines policy and helps reach national breastfeeding targets. Only 21% (66/317) of Australian hospitals are BFHI accredited. OBJECTIVE: To examine the factors perceived to promote or hinder BFHI accreditation. METHOD: Focus group interviews explored opinions of 31 participants, in differing roles and levels of employment, across midwifery, medical, nursing and ancillary staff at six South Australian maternity hospitals. RESULTS: The results suggest that staffs' understanding and personal views are often discordant with BFHI aims. Perceived difficulties include the accreditation process, hospital dynamics, and the Ten Steps implementation plus a bottle feeding culture and maternal employment that impact upon continued breastfeeding. CONCLUSIONS: Upper management support, specific funding, a dedicated co-ordinator with "area leaders", development of a specific breastfeeding policy incorporating various disciplines and staff, containing detailed protocols that comply with the International Code of Marketing of Breast Milk Substitutes and subsequent World Health Assembly (WHA) resolutions, are all required. Staff and mothers require multiple modes of education to understand the BFHI, including sponsorship for training of lactation consultants. Full implementation of BFHI across Australia will assist the development of nationally accepted breastfeeding definitions, improve monitoring and evaluation of rates and practices, and improve breastfeeding outcomes. PMID- 20571903 TI - Activation of PPARdelta promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated beta-cells. AB - The peroxisome proliferator-activated receptor delta (PPARdelta) regulates the expression of genes involved in cellular lipid and cell energy metabolism in many metabolically active tissues, such as liver, muscle, and fat, and plays a role in the cellular response to stress and environmental stimuli. The particular role of PPARdelta in insulin-secreting beta-cells, however, is not well understood; we recently identified the cell-specific role of PPARdelta on mitochondrial energy metabolism and insulin secretion in lipotoxic beta-cells. After treatment of HIT T15 cells, a syrian hamster pancreatic beta-cell line, with high concentrations of palmitate and/or the specific PPARdelta agonist GW501516, we detected the gene expression changes for transcripts, such as peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1alpha), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), the protein levels of the mitochondria uncoupling protein 2 (UCP2), mitochondrial morphology, the insulin secretion capacity and ATP/ADP ratio. Our results show that GW501516 treatment promoted generation of mitochondrial ATP, as well as expression levels of PGC 1alpha, NRF-1 and mtTFA, decreased basal insulin secretion, but had no effect on glucose-stimulated insulin secretion (GSIS), increased amounts of UCP2 and changed ATP-to-ADP ratio, improved mitochondrial morphology in palmitate-treated beta-cells. GW501516-induced activation of PPARdelta enhanced mitochondrial energy metabolism, but also promoted a concomitant mitochondrial uncoupling and resulted in decreased basal insulin secretion and restricted GSIS; this observation indicated the possible action of a protective mechanism responding to the alleviation of excessive lipid load and basal insulin secretion in lipotoxic beta-cells. PMID- 20571904 TI - Stable knockdown of TPPP3 by RNA interference in Lewis lung carcinoma cell inhibits tumor growth and metastasis. AB - Tubulin polymerization promoting protein 3 (TPPP3), a member of the TPPP family, can induce tubulin polymerization and microtubule bundling. Previously, it has been shown that TPPP3 plays an important role in cell proliferation. Depletion of TPPP3 by microRNA-based RNA interference (RNAi) inhibits cell growth, arrests cell cycles, and causes mitotic abnormalities in HeLa cells. In the present study, we knocked down TPPP3 in Lewis lung carcinoma (LLC) cells with the same RNAi construct, and observed a retarded tumor cell growth in vitro. Furthermore, C57BL/6 mice that received subcutaneously injected LLC cells in which TPPP3 was knocked down showed a pronounced reduction in tumor progression. The migration/invasion activity of TPPP3-knockdown LLC cells was significantly suppressed in a transwell chamber migration assay. When these cells were injected into the tail veins of C57BL/6 mice, they exhibited milder lung metastasis compared with control tumor cells. Taken together, these findings suggested that the TPPP3 gene played an important role in tumorigenesis and metastasis, and it could potentially become a novel target for cancer therapy. PMID- 20571905 TI - Culture, stress and recovery from schizophrenia: lessons from the field for global mental health. AB - This cultural case study investigates one U.S. psychosocial rehabilitation organization's (Horizons) attempt to implement the recovery philosophy of the U.S. Recovery Movement and offers lessons from this local attempt that may inform global mental health care reform. Horizons' "recovery-oriented" initiatives unwittingly mobilized stressful North American discourses of valued citizenship. At times, efforts to "empower" people diagnosed with schizophrenia to become esteemed self-made citizens generated more stressful sociocultural conditions for people whose daily lives were typically remarkably stressful. A recovery-oriented mental health system must account for people diagnosed with schizophrenia's sensitivity to stress and offer consumers contextually relevant coping mechanisms. Any attempt to export U.S. mental health care practices to the rest of the world must acknowledge that (1) sociocultural conditions affect schizophrenia outcomes; (2) schizophrenia outcomes are already better in the developing world than in the United States; and (3) much of what leads to "better" outcomes in the developing world may rely on the availability of locally relevant techniques to address stress. PMID- 20571907 TI - PIK3CA mutations in KRAS and BRAF wild type colorectal cancer patients. A study of Spanish population. AB - The objective of the work was to study PIK3CA mutations in wild type KRAS and BRAF colorectal cancer. Clinicopathological data and paraffin-embedded specimens were collected on 73 patients who underwent colorectal resections at General Yague Hospital in Burgos. KRAS, BRAF and PIK3CA status were analyzed by real-time PCR in all patients. PIK3CA mutations were present in 8.22% of wild type KRAS and BRAF colorectal cancers. The most frequent mutation is E545K/D in exon 9 which represents 83.3% of all mutations. By contrast, we did not found any tumour harbouring H1047R mutation in exon 20. Among the patients who undergo a curative resection of colorectal cancer, PIK3CA mutation is present in an important percentage of KRAS and BRAF wild type tumours. PIK3CA mutation may be considered as it could be a hypothetic reason to be not responder to anti-EGFR antibodies. PMID- 20571906 TI - Lactobacillus plantarum prevents the development of colitis in IL-10-deficient mouse by reducing the intestinal permeability. AB - It is reported that defects exist in the small intestinal epithelial barrier of inflammatory bowel disease, which might be associated with increased intestinal permeability at a very early stage. Our study aims to investigate the role of Lactobacillus plantarum on the decrease of epithelial permeability and the further protective effects on the intestinal epithelial barrier using the IL-10 deficient mouse model. Our study showed that tight junction associated proteins were increased after the pre-treatment of L. plantarum by fluorescence staining, western blot, real-time PCR and transmission electron microscope. Oral gavage of milk containing L. plantarum was effective in decreasing small intestinal permeability using methods of Ussing chamber assay and sugar probe. Assay of pro inflammatory cytokines IFN-gamma, TNF-alpha, MPO, and colonic histology by ELISA showed protective effects of L. plantarum on the intestinal epithelial barrier. Therefore, L. plantarum may prevent the development of colitis in IL-10-deficient mice by blocking changes in the expression of TJ proteins, TJ structure and intestinal permeability. PMID- 20571908 TI - MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study. AB - In the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR restriction fragment length polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19-2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07-10.05) variants of the OGG1 gene. The gene-gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25 3.11), (OR 3.54; 95% CI 1.39-9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non smoking status in HNSCC (OR 0.34; 95% CI 0.17-0.66). We also found a link between gene-gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17-4.20 and 2.18-5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population. PMID- 20571909 TI - The effect of oncoprotein v-erbA on thyroid hormone-regulated genes in hepatocytes and their potential role in hepatocellular carcinoma. AB - Mutant forms of thyroid hormone receptor (TR) with dominant negative activity are frequently found in human hepatocellular carcinoma (HCC). Interestingly, the v erbA oncogene, known to exert a dominant-negative effect on the expression of thyroid hormone (T3)-responsive genes, led to the development of HCC in a transgenic mouse model. Thus it is possible that the oncogenic activity of v-erbA in hepatocytes may be mediated by its dominant negative activity on T3-responsive genes. Microarray analysis was used to identify genes differentially expressed in murine hepatocytes in culture (AML12 cells) stably transfected with v-erbA and exposed to T3. The Affymetrix GeneChip Mouse Genome 430 2.0 array consisted of over 39,000 transcripts representing well-known genes. We have identified twenty T3-responsive genes that are negatively regulated by v-erbA at 3 h, and eighteen genes at 24 h, such as follistatin, activin betaC, thrombomodulin, Six1, Rasgrp3 and Ndrg2, as well as genes that are regulated by v-erbA only, such as angiopoietin 1 and Igfr2. We have identified T3 responsive genes that are dysregulated by v-erbA. These genes are known to be involved in carcinogenesis. Our studies may provide insight into the potential role of mutant forms of TR in the pathogenesis of HCC. PMID- 20571910 TI - PMS1 from Arabidopsis thaliana: optimization of protein overexpression in Escherichia coli. AB - One of the major limitations when attempting to obtain detailed biochemical, biophysical and immunological characterization of plant DNA mismatch repair proteins is their extremely low abundance in vivo under normal growth conditions. An initial analysis of PMS1 transcript level in various Arabidopsis thaliana tissues was carried out by quantitative real-time RT-PCR. For calli, flowers and seedlings, the corresponding cDNA copies per ng RNA were 66.9, 3.1 and 2.7, respectively. This suggests an important role of this gene in rapidly dividing tissues. In order to obtain a high level of PMS1 from Arabidopsis thaliana, the protein production was successfully optimized in an Escherichia coli host. The corresponding coding sequence of PMS1 was inserted into pET28a downstream a hexa histidyl leader sequence. The pET28a-AtPMS1 plasmid was efficiently expressed in JM109(DE3)-pRIL strain probably due to the genotype features of the cells (endA1, recA1, relA1, Delta(lac-proAB), laqIqZDeltaM15) and the presence of extra copies of argU, ileY, and leuW tRNA genes, which encode the RIL codons. This strategy has allowed us to obtain His-tagged PMS1 at about 7% of the total soluble E. coli cell protein. The protein was purified by standard Ni(+) affinity chromatography procedures and the electrophoretically homogeneous preparation was used as an antigen for antibody generation in rabbits. This approach provides effective tools for a further reconstitution of plant mismatch repair (MMR) system in vitro and for the analysis of protein expression and distribution of AtPMS1 in various tissues after different treatments (e.g. DNA mutagens). PMID- 20571911 TI - Analysis of the differential expression of the genes related to Brassica napus seed development. AB - To screen the genes related to Brassica napus seed development at pattern formation and maturation stages, the suppression subtractive cDNA libraries of B. napus cultivar Zhongshuang 6 were constructed with its embryos at 10 days after flowering (10 DAF) and 30 days after flowering (30 DAF) through suppression subtractive hybridization (SSH) technology. The positive clones were screened by PCR and dot blot hybridization, and then sequenced. High quality expressed sequence tags (ESTs) were used for COG functional classification with COGNITOR software, as well as analysis and annotation with BLAST software. Tissue-specific detection of five genes screened was performed by RT-PCR in root, stem, leaf, flower, bud, pod, and embryo tissues. The insert size ranged from 100 to 900 bp, with an average size of about 500 bp. According to COG functional classification database, the differentially expressed genes mainly involved in lipid and amino acid metabolism, signal transduction, post-transcriptional modification, and etc. The results from RT-PCR detection of the five differentially expressed genes indicated that genes 2-96 and 2-352 presented embryo-specific expression, gene 1 385 expressed in parts of tissues, and genes 1-71 and 1-682 expressed in all tissues. Two genes were found to be involved in seed development, lipid and protein metabolisms, two genes may be involved in signal transduction, one gene could not match with the homologous sequences known to date and was likely a new gene. These results are helpful for future gene cloning and their functional analysis. PMID- 20571912 TI - Disruption of homocitrate synthase genes in Candida albicans affects growth but not virulence. AB - Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway, were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Delta/lys22Delta mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued by the addition of 0.5-0.6 mM L: -lysine. On the other hand, its virulence in vivo in the model of disseminated murine candidiasis appeared identical to that of the mother, wild type strain. These findings strongly question a possibility of exploitation of homocitrate synthase and possibly also other enzymes of the lysine biosynthetic pathway as targets in chemotherapy of disseminated fungal infections. PMID- 20571913 TI - Persistence of Isaria fumosorosea (Hypocreales: Cordycipitaceae) SFP-198 conidia in corn oil-based suspension. AB - Long-term persistence of entomopathogenic fungi as biopesticides is a major requirement for successful industrialization. Corn oil carrier was superior in maintaining germination rates of Isaria fumosorosea SFP-198 conidia during exposure to 50 degrees C for 2 h, when compared with other oils, such as soybean oil, cottonseed oil, paraffin oil, and methyl oleate. The corn oil-based conidial suspension (91.6% germination) was also better in this regard than conidial powder (28.4% germination) after 50 degrees C for 8 h. Long-term storage stabilities of corn oil-based conidial suspension and conidial powder at 4 and 25 degrees C for 24 months were investigated, based on the correlation of germination rate with insecticidal activity against greenhouse whiteflies, Trialeurodes vaporariorum. Viability of conidia in corn oil was more than 98.4% for up to 9 months of storage at 25 degrees C, and followed by 23% at 21 months. However, conidial powder had only 34% viability after 3 months of storage at 25 degrees C, after which its viability rapidly decreased. The two conidial preparations stored at 4 degrees C had better viabilities than those at 25 degrees C, showing the same pattern as above. These results indicate that corn oil-based conidial suspension can be used to improve conidial persistence in long term storage and be further applied to the formulation of other thermo susceptible biological control agents. PMID- 20571915 TI - Workshop OQOL'09: Open Questions on the Origins of Life 2009, Palacio Miramar, San Sebastian-Donostia, Spain, May 20-23, 2009. Abstracts. PMID- 20571914 TI - Protective effects of flavonoids against oxidative stress induced by simulated microgravity in SH-SY5Y cells. AB - Many lines of evidence suggest that microgravity results in increased oxidative stress in the nervous system. In order to protect neuronal cells from oxidative damage induced by microgravity, we selected some flavonoids that might prevent oxidative stress because of their antioxidant activities. Among the 20 flavonoids we examined, we found that isorhamnetin and luteolin had the best protective effects against H(2)O(2) or SIN-1-induced cytotoxicity in SH-SY5Y cells. Using a clinostat to simulate microgravity, we found that isorhamnetin and luteolin treatment protected SH-SY5Y cells by preventing microgravity-induced increases in reactive oxygen species (ROS), nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels, and a decrease in antioxidant power (AP). Moreover, isorhamnetin and luteolin treatment downregulated the expression of inducible nitric oxide synthase (iNOS), and oxidative stress was significantly inhibited by an iNOS inhibitor in SH-SY5Y cells exposed to simulated microgravity (SMG). These results indicate that isorhamnetin and luteolin could protect against microgravity induced oxidative stress in neuroblastoma SH-SY5Y cells by inhibiting the ROS-NO pathway. These two flavonoids may have potential for preventing oxidative stress induced by space flight or microgravity. PMID- 20571916 TI - Extent of storage and wastage of antibacterial agents in Palestinian households. AB - OBJECTIVE: Inappropriate use of antibacterial agents may lead to drug wastage and potential therapeutic failures in the future. The objective of this study was to investigate the extent of storage, and wastage of antibacterial agents in households in Palestine. METHOD: This was a cross sectional, questionnaire-based study of households in northern Palestine. Any antibacterial agents present in the surveyed households were investigated and family members were interviewed. MAIN OUTCOME MEASURE: Number and type of antibacterial agents stored in each household. RESULTS: The total number of antibacterial agents in the 465 surveyed households was 641, constituting 11.3% of the total stored medications. The average number of antibacterial agents was 1.4 +/- 1.74 per household. The most common antibacterial agents encountered were amoxicillin (29.5%) and amoxicillin/clavulanic acid (11.6%). Family size (P < 0.001), total number of stored medications (P < 0.001), and presence of elderly residents (>65 years) (P < 0.001) were significantly associated with the presence of antibacterial agents. Furthermore, the level of parental education was significantly and positively (P = 0.009, r = 0.128; P = 0.013, r = 0.122 for father and mother respectively) correlated with the number of antibacterial agents found in the households. More than one-third (37.4%) of antibacterial agents were stored within the reach of children. Wasted antibacterial agents, defined as those which had expired or those with no clear expiry date were 16.4 and 10.1%, respectively. The percentage of antibacterial agents that were not currently in use was 69.3%. Estimated total value of antibacterial agents found in the study was $4,769, approximately $11.5 per household. The total wastage of antibacterial agents was valued at $2,790, approximately $6.7 per household. CONCLUSION: Antibacterial agents were commonly encountered in Palestinian households, and a relatively large percentage was being wasted. PMID- 20571917 TI - The relationship between parental overprotection and health-related quality of life in pediatric cancer: the mediating role of perceived child vulnerability. AB - PURPOSE: The current study sought to examine the relation of parental overprotection and perceived child vulnerability to parent-reported health related quality of life in parents of children with cancer. METHODS: Parents (N = 89) of children who had been diagnosed with cancer completed measures of parental overprotection, perceived child vulnerability, and parent-proxy report of health related quality of life. RESULTS: After controlling for theoretically relevant covariates, parental overprotection and perceived child vulnerability were both found to be significantly related to child health-related quality of life. Additional analyses revealed that perceived child vulnerability mediated the relationship between overprotective parenting behaviors and the child's health related quality of life. CONCLUSION: The findings highlight the need to assess for these discrete parenting variables in parents of children with cancer and to develop interventions to target parental perceptions of vulnerability. PMID- 20571918 TI - Impact of socioeconomic and clinical factors on child oral health-related quality of life (COHRQoL). AB - PURPOSE: Child oral health-related quality of life (COHRQoL) has been increasingly assessed; however, few studies appraised the influence of socioeconomic status on COHRQoL in developing countries. This study assessed the relationship of COHRQoL with socioeconomic backgrounds and clinical factors. METHODS: This study followed a cross-sectional design, with a multistage random sample of 792 schoolchildren aged 12 years, representative of Santa Maria, a southern city in Brazil. Participants completed the Brazilian version of the Child Perceptions Questionnaire (CPQ(11-14)), their parents or guardians answered questions on socioeconomic status, and a dental examination provided information on the prevalence of caries, dental trauma and occlusion. The assessment of association used hierarchically adjusted Poisson regression models. RESULTS: Higher impacts on COHRQoL were observed for children presenting with untreated dental caries (RR 1.20; 95% CI 1.07-1.35) and maxillary overjet (RR 1.19; 95% CI 1.02-1.40). Socioeconomic factors also associated with COHRQoL; poorer scores were reported by children whose mothers have not completed primary education (RR 1.30; 95% CI 1.17-1.44) and those with lower household income (RR 1.13; 95% CI 1.02-1.26). CONCLUSION: Poor socioeconomic standings and poor dental status have a negative impact on COHRQoL; reducing health inequalities may demand dental programmes and policies targeting deprived population. PMID- 20571919 TI - Successful use of fondaparinux in a patient with a mechanical heart valve replacement and a history of heparin-induced thrombocytopenia. AB - The development of heparin-induced thrombocytopenia (HIT) is an antibody-mediated clinicopathologic syndrome. The resultant thrombocytopenia and thrombosis can be severe and life-threatening. Fondaparinux is a parenteral factor Xa inhibitor used for venous thromboembolism prevention and treatment. Fondaparinux has minimal affinity for platelet factor 4, making it an alternative agent to unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) and a plausible consideration for patients with a history of HIT. The use of fondaparinux in patients with mechanical heart valve replacement and a history of HIT has never been discussed in the literature. We report on the case of a patient with a mechanical aortic heart valve replacement and a history of HIT who was successfully bridged postoperatively with fondaparinux. While there is currently no literature to support the use of fondaparinux in patients with mechanical heart valves, this drug may offer an option for management of such patients who cannot use heparin products. However, further clinical investigations are warranted to confirm both the safety and efficacy of this agent in the mechanical heart valve population. PMID- 20571920 TI - Safety of immediate reversal of anticoagulation by protamine to reduce bleeding complications after infarct artery stenting for acute myocardial infarction and adjunctive abciximab therapy. AB - Infarct artery stenting with adjunctive abciximab therapy is widely used treatment for patients with acute myocardial infarction (AMI). However, bleeding complications have been associated with a worse clinical outcome. Randomized trials in elective patients have shown that postprocedural protamine administration is safe and associated with a significant reduction in bleeding complications. The aim of the current study was to evaluate in STEMI patients undergoing primary percutaneous coronary intervention (PCI) with abciximab and stenting whether immediate reversal of anticoagulation by protamine is safe and associated with a reduction in the occurrence of bleeding complications. From January 2004 to June 2005, 254 patients with STEMI had immediate reversal of anticoagulation by protamine administration after infarct artery stenting and received abciximab therapy without heparin infusion (Group 1). These patients were compared with a control group of 265 patients (June 2002-December 2003) treated with the standard heparin therapy: bolus in order to achieve an activated coagulation time of 250-300 s during PCI plus 12-h infusion (7 UI/kg/h; Group 2). We excluded patients undergoing IABP implantation. The two groups were similar in all baseline characteristics. There were no differences in in-hospital mortality, reinfarction, urgent target vessel revascularization, stroke or acute or subacute stent thrombosis, while Group 1 patients showed a lower incidence of major bleeding complications (ACUITY scale: 1.1 vs. 4.0%, P = 0.035) and a shorter length of hospital stay (3.5 +/- 1.7 vs. 4.0 +/- 1.6 days, P = 0.002) as compared with heparin treated patients. Among patients undergoing primary stenting with abciximab administration, immediate post-PCI reversal anticoagulation by protamine without associated heparin infusion is safe and associated with a significant reduction in major bleeding complications. PMID- 20571921 TI - Adaptability and growth of Malpura ewes subjected to thermal and nutritional stress. AB - A study was conducted to assess the effect of combined stresses (thermal and nutritional) on physiological adaptability and growth performance of Malpura ewes. Twenty-eight adult Malpura ewes (average BW 33.56 kg) were used in the present study. The ewes were divided into four groups, viz., GI (n=7; control), GII (n=7; thermal stress), GIII (n=7; nutritional stress), and GIV (n=7; combined stress). The animals were stall-fed with a diet consisting of 60% roughage and 40% concentrate. GI and GII ewes were provided with ad libitum feeding, while GIII and GIV ewes were provided with restricted feed (30% intake of GI ewes) to induce nutritional stress. GII and GIV ewes were kept in climatic chamber at 40 degrees C and 55% RH for 6 h/day between 1000 and 1600 hours to induce thermal stress. The study was conducted for a period of two estrus cycles. The parameters studied were feed intake, water intake, physiological responses (viz., respiration rate, pulse rate, and rectal temperature), body weight, and body condition scoring (BCS) of ewes. Both thermal and combined stress significantly (P<0.05) affected the feed intake, water intake, respiration rate, and rectal temperature. The feeding schedule followed in the experiment significantly (P<0.05) altered the body weight and BCS between the groups. The results reveal that when compared with thermal stress, nutritional stress had less significant effect on the parameters studied. However, when both these stresses were coupled, it had a significant influence on all the parameters studied in these ewes. It can be concluded from this study that when two stressors occur simultaneously, the total cost may have severe impact on biological function. PMID- 20571922 TI - Plasma pharmacokinetics and milk levels of ceftriaxone following single intravenous administration in healthy and endometritic cows. AB - Pharmacokinetics and milk levels of ceftriaxone were studied in healthy and endometritic cows following single intravenous administration. The drug was detected up to 8 h of dosing in plasma of healthy and endometritic cows and the drug disposition followed three-compartment open model. The values of Vd(area), AUC, t(1/2beta), Cl(B), MRT and P/C ratio were 0.50 +/- 0.19 L.kg(-1), 62.2 +/- 23.3 microg.ml(-1).h, 1.02 +/- 0.07 h, 0.30 +/- 0.09 L.kg(-1).h(-1), 1.55 +/- 0.25 h and 0.52 +/- 0.27, respectively, in healthy and 1.55 +/- 0.52 L.kg(-1), 37.0 +/- 17.1 microg.ml(-1).h, 1.56 +/- 0.25 h, 0.56 +/- 0.14 L.kg(-1).h(-1), 2.14 +/- 0.34 h and 1.44 +/- 0.60, respectively, in endometritic cows. The drug was detected in milk for 36 h after administration. For MIC(90) of 0.5 microg.ml( 1) the most appropriate dosage for ceftriaxone, would be 9.0 mg.kg(-1) repeated at 6 h intervals for the treatment of endometritis in cows. PMID- 20571923 TI - Uptake decrease of proliferative PET tracer 18FLT in bone marrow after carbon ion therapy in lung cancer. AB - PURPOSE: The aim of this study was to investigate the change of 3'-[18F]fluoro-3' deoxy-L: -thymidine (18FLT) uptake in normal bone marrow (BM) after inevitable radiation. PROCEDURES: Twenty-one non-small cell lung cancer patients who received carbon ion radiotherapy (CIRT) were studied with 18FLT-positron emission tomography/computed tomography (PET/CT) at pre- and post-CIRT. Radiation dose was calculated by radiation planning. Irradiated BM was divided into three groups (<10% of maximum dose, 10-30%, and >30%). RESULTS: 18FLT uptake clearly decreased at >10% irradiated areas and mildly decreased at <10% areas. 18FLT uptake was lowest just after CIRT, somewhat increased at 3 months, and remained unchanged for more than 1 year. There was no significant difference between 10-30% and >30% areas. CONCLUSION: 18FLT revealed that BM function decreased by small dose such as <4.2-4.4 GyE/1 fraction of CIRT and is eradicated by >4.2-4.4 GyE/1 fraction. PMID- 20571924 TI - Factors associated with mental health services use among disconnected African American young adult population. AB - Research related to mental health service use among vulnerable young adults is limited. This study used an expanded version of Andersen's Behavioral Model of Health Services Use to evaluate factors associated with the use of different types of mental health services among a sample of predominantly African-American 16-24 year olds (n = 500) in an employment training program in Baltimore City. Results indicated that participants were more likely to have received mental health services in correctional facilities than in community- or school-based contexts. Use of mental health services in correctional facilities was significantly greater among males, those less than 18 years, and those who experienced more stressful events. Findings illustrate the need to develop seamless mental health services for vulnerable young adults in multiple contexts, including the criminal justice system. PMID- 20571925 TI - Juglanone, a novel alpha-tetralonyl derivative with potent antioxidant activity from Juglans mandshurica. AB - A novel alpha-tetralonyl derivative, juglanone, was isolated from the fresh unripe fruits of Juglans mandshurica. Its structure was determined by spectroscopic analyses and from chemical evidence. Juglanone exhibited significant antioxidant activity in assays for 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and superoxide dismutase-like activity with IC(50) values of 10.1 and 9.0 microM, respectively. It also showed moderate cytotoxic activity against HL-60 human myeloid leukemia with an IC(50) value of 19.7 microM. PMID- 20571926 TI - Megastigmane glucosides and an unusual monoterpene from the leaves of Cananga odorata var. odorata, and absolute structures of megastigmane glucosides isolated from C. odorata var. odorata and Breynia officinalis. AB - From a 1-BuOH-soluble fraction of a MeOH extract of Cananga odorata var. odorata, collected at the Botanical Garden of Chiang Mai University, a new megastigmane glucoside, named canangaionoside, and an irregular monoterpene were isolated. A known compound, breyniaionoside A, which has been obtained from the leaves of Breynia officinalis, was also isolated, and its absolute structure was substantiated for the first time in this study. On this occasion, the absolute stereochemistries of structurally related megastigmane glucosides, breyniaionosides B and C, isolated from B. officinalis were examined. PMID- 20571927 TI - Validation and prediction of traditional Chinese physical operation on spinal disease using multiple deformation models. AB - PURPOSE: Traditional Chinese medical massage is a physical manipulation that achieves satisfactory results on spinal diseases, according to its advocates. However, the method relies on an expert's experience. Accurate analysis and simulation of massage are essential for validation of traditional Chinese physical treatment. The objective of this study is to provide analysis and simulation that can reproducibly verify and predict treatment efficacy. METHODS: An improved physical multi-deformation model for simulating human cervical spine is proposed. First, the human spine, which includes muscle, vertebrae and inter- vertebral disks, are segmented and reconstructed from clinical CT and MR images. Homogeneous landmark registration is employed to align the spine models before and after the massage manipulation. Central line mass spring and contact FEM deformation models are used to individually evaluate spinal anatomy variations. The response of the human spine during the massage process is simulated based on specific clinical cases. RESULTS: Ten sets of patient data, including muscle force relationships, displacement of vertebrae, strain and stress distribution on inter-vertebral disks were collected, including the pre-operation, post-operation and the 3-month follow-up. The simulation results demonstrate that traditional Chinese massage could significantly affect and treat most mild spinal disease. CONCLUSION: A new method that simulates a traditional Chinese medical massage operation on the human spine may be a useful tool to scientifically validate and predict treatment efficacy. PMID- 20571928 TI - Sociodemographics and comorbidities influence decisions to undergo pancreatic resection for neoplastic lesions. AB - INTRODUCTION: Pancreatic resection is being performed with increasing frequency and safety. Technical outcomes and long-term survival for neoplastic lesions are well reported; however, reasons why patients do not undergo surgery for potentially resectable lesions are not well understood. The aim of this study was to determine the factors contributing to the decision not to operate for resectable pancreatic neoplasms. METHODS: From 2004 to 2008, all patients with resectable pancreatic neoplasms at a single high-volume hepatopancreaticobiliary center were evaluated. The impact of patient factors, sociodemographics, medical comorbidities (Charlson combined comorbidity index (CCI) and ACCI), disease factors (tumor characteristics), and surgical factors (type of resection required) on the decision to undergo pancreatectomy were analyzed using univariate and multivariate binary logistic regression analysis. RESULTS: Three hundred seventy-five patients with resectable pancreatic lesions were identified. The median age was 62 years (21-93); 203 out of 375 (54.1%) were males. Fifty five (14.7%) did not undergo resection. On univariate analysis, age (odds ratio (OR) 1.116, p < 0.001), non-English speaking background (NESB; OR 4.276, p = 0.001), tumor type (p = 0.001 increased for cystic neoplasms including intraductal papillary mucinous neoplasm), CCI score (OR 1.239, p = 0.001), and ACCI score (OR 1.433, p < 0.001) were associated with an increased risk of not undergoing resection. Gender, age, marital status, and urban residence were not predictive. On multivariate analysis, NESB (p = 0.018) and the ACCI (p = 0.002) remained predictive of not undergoing resection. The majority of patients did not undergo surgery because the patient declined in 25 out of 55 (45.5%), and resection was not offered in 15 out of 55 (27.3%). In the remainder, medical contraindications precluded surgery. Advanced age, tumor type, comorbidities (27.3%), age (21.8%), surgical risk (29.1%), frailty (18.2%), and uncertain diagnosis (5.5%) were cited as reasons for not proceeding with surgery. CONCLUSION: Patients with a higher ACCI and those from a NESB are less likely to undergo surgery for resectable neoplastic lesions of the pancreas. These factors must be taken into consideration in the decision-making process when considering surgery for patients with pancreatic neoplasms. Novel strategies should be employed to optimize access to surgery for patients with resectable pancreatic neoplasms. PMID- 20571929 TI - Adherence to cardiovascular disease medications: does patient-provider race/ethnicity and language concordance matter? AB - BACKGROUND: Patient-physician race/ethnicity and language concordance may improve medication adherence and reduce disparities in cardiovascular disease (CVD) by fostering trust and improved patient-physician communication. OBJECTIVE: To examine the association of patient race/ethnicity and language and patient physician race/ethnicity and language concordance on medication adherence rates for a large cohort of diabetes patients in an integrated delivery system. DESIGN: We studied 131,277 adult diabetes patients in Kaiser Permanente Northern California in 2005. Probit models assessed the effect of patient and physician race/ethnicity and language on adherence to CVD medications, after controlling for patient and physician characteristics. RESULTS: Ten percent of African American, 11 % of Hispanic, 63% of Asian, and 47% of white patients had same race/ethnicity physicians. 24% of Spanish-speaking patients were linguistically concordant with their physicians. African American (46%), Hispanic (49%) and Asian (52%) patients were significantly less likely than white patients (58%) to be in good adherence to all of their CVD medications (p<0.001). Spanish-speaking patients were less likely than English speaking patients to be in good adherence (51% versus 57%, p<0.001). Race concordance for African American patients was associated with adherence to all their CVD medications (53% vs. 50%, p<0.05). Language concordance was associated with medication adherence for Spanish speaking patients (51% vs. 45%, p<0.05). CONCLUSION: Increasing opportunities for patient-physician race/ethnicity and language concordance may improve medication adherence for African American and Spanish-speaking patients, though a similar effect was not observed for Asian patients or English-proficient Hispanic patients. PMID- 20571930 TI - Biochemical studies on sphingolipid of Artemia franciscana (I) isolation and characterization of sphingomyelin. AB - Sphingomyelin was isolated from cysts of the brine shrimp Artemia franciscana using QAE-Sephadex A25, Florisil and Iatrobeads column chromatographies. The chemical structure was identified using thin-layer chromatography, gas-liquid chromatography, infrared spectroscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The ceramide moiety of sphingomyelin consisted of stearic, arachidic, and behenic acids as fatty acids, and hexadeca-4 and heptadeca-4-sphingenines as sphingoids. By comparative analysis, the ceramide component of Artemia sphingomyelin appears unique in invertebrates and vertebrates. Biological functions of sphingomyelin have largely been investigated using mammalian-derived sphingomyelin. In mammals, a wide variety of molecular species of sphingomyelins have been reported, especially derived from nerve tissue, while the lower animal Artemia contains this unusual sphingomyelin perhaps because of having a much simpler nervous system. The purified unusual sphingomyelin derived from Artemia franciscana might be a very useful tool in elucidating the functions and mechanisms of action of this mediator. PMID- 20571933 TI - Tarenflurbil in patients with mild Alzheimer's disease. PMID- 20571931 TI - Fertility among testicular cancer survivors: a case-control study in the U.S. AB - INTRODUCTION: Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility. METHODS: To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted. The men were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008-2009. RESULTS: TGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99-13.76) and difficulty in fathering children (OR 6.41; 2.72-15.13). Cases were also more likely to be tested for infertility (OR 3.65; 95% CI 1.55-8.59). Cases, however, did not differ from controls in actually fathering children (OR 1.37; 95% CI 0.88-2.15). These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery plus-chemotherapy. DISCUSSION: While expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men. It is possible that treatment for TGCT does not permanently affect fertility or, alternatively, that TGCT survivors attempt to father children with greater persistence or at younger ages than do other men. PMID- 20571932 TI - The relationship of x-linked primary immune deficiencies and autoimmunity. AB - It is well-known that autoimmunity is significantly more prevalent in females. Growing evidence indicates that genes located on the X chromosome may play a role in autoimmunity and immune dysregulation, as also indicated by the frequent association of autoimmune phenomena in patients with X-linked primary immune deficiencies (PIDs). Hence, this group of genetic disorders is of particular interest to study PID-causing genes in the setting of more complex autoimmune disorders. This review focuses on the mechanisms leading to the autoimmune phenomena that are associated with the different X-linked PIDs, and on the intriguing interplay between immune dysregulation and immune deficiency in this unique setting. PMID- 20571934 TI - Heavy metals in Antarctic notothenioid fish from South Bay, Livingston Island, South Shetlands (Antarctica). AB - The Pb, Cd, Cu, Zn, and Mn contents of the liver, spleen, muscle, bones, scales, gills, and the whole body of 3- to 7-year-old notothenioid Antarctic cod (Notothenia coriiceps, Richardson, 1844) were measured. The highest heavy metal concentrations obtained are as follows: Cd in liver, the mean value was 1.36 +/- 0.19 mg/kg dry weight (wt); Pb and Zn in spleen, the mean values were 3.33 +/- 0.86 and 143.97 +/- 16.17 mg/kg dry wt, respectively; Cu in gills, 3.76 +/- 1.16 mg/kg dry wt; and Mn in scales, 14.80 +/- 4.77 mg/kg dry wt. The comparison with the data reported up to now shows that the metal concentrations varied within relative wide ranges. These first data obtained could be used as a baseline to investigate further relationships among metal contents in fish, their diet, and habitat. PMID- 20571935 TI - Alterations of the sphingolipid pathway in Alzheimer's disease: new biomarkers and treatment targets? AB - The public health burden of Alzheimer disease (AD), the most common neurodegenerative disease, threatens to explode in the middle of this century. Current FDA-approved AD treatments (e.g. cholinesterase inhibitors, NMDA-receptor agonists) do not provide a "cure", but rather a transient alleviation of symptoms for some individuals. Other available therapies are few and of limited effectiveness so additional avenues are needed. Sphingolipid metabolism is a dynamic process that modulates the formation of a number of bioactive metabolites, or second messengers critical in cellular signaling and apoptosis. In brain, the proper balance of sphingolipids is essential for normal neuronal function, as evidenced by a number of severe brain disorders that are the result of deficiencies in enzymes that control sphingolipid metabolism. Laboratory and animals studies suggest both direct and indirect mechanisms by which sphingolipids contribute to amyloid-beta production and Alzheimer pathogenesis but few studies have translated these findings to humans. Building on the laboratory and animal evidence demonstrating the importance of sphingolipid metabolism in AD, this review highlights relevant translational research incorporating and expanding basic findings to humans. A brief biological overview of sphingolipids (sphingomyelins, ceramides, and sulfatides) in AD is first described, followed by a review of human studies including post-mortem studies, clinical and epidemiological studies. Lastly, the potential role of peripheral ceramides in AD pathogenesis is discussed, as well as the possible use of sphingolipids as biomarkers for AD. PMID- 20571936 TI - Angiogenesis and clinicopathologic characteristics in different hepatocellular carcinoma subtypes defined by EpCAM and alpha-fetoprotein expression status. AB - Recently, two hepatic lineage markers epithelial cell adhesion molecule (EpCAM) and alpha-fetoprotein (AFP) were used to classify hepatocellular carcinoma (HCC) into four subtypes with prognostic implication. In the present study, we further evaluated the clinicopathologic and angiogenic characteristics among these HCC subtypes. EpCAM expression was investigated by immunohistochemistry in 115 HCC primary tumors. Based on EpCAM immunostaining and serum AFP levels, 115 HCC cases were classified into four subtypes: EpCAM+AFP+ (26.1%), EpCAM-AFP+ (20.0%), EpCAM+AFP- (20.8%), and EpCAM-AFP- (33.1%). EpCAM+AFP+ and EpCAM-AFP+ HCC were associated with late TNM stages and high frequencies of venous invasion, whereas EpCAM+AFP- and EpCAM-AFP- subtypes were associated with early TNM stages and low frequencies of venous invasion. Furthermore, EpCAM+AFP+ HCC had a significantly higher microvessel density (MVD) and higher level of VEGF (Vascular epithelial growth factor) expression than the other three subtypes. In conclusion, our study indicated that subtype classification of HCC based on EpCAM and AFP status had clinicopathologic and biologic implications in aggressive phenotype and angiogenesis. We also suggest that the EpCAM+AFP+ HCC patients might be potential therapeutic candidates for anti-angiogenesis therapy. PMID- 20571937 TI - Simultaneous targeting of Requiem & Alg-2 in Chinese hamster ovary cells for improved recombinant protein production. AB - Apoptosis is known to be the main cause of cell death in the bioreactor environment, leading to the loss of recombinant protein productivity. In a previous study, transcriptional profiling was used to identify and target four early apoptosis-signaling genes: FADD, FAIM, Alg-2, and Requiem. The resulting cell lines had increased viable cell numbers and extended culture viability, which translated to increased protein productivity. Combinatorial targeting of two genes simultaneously has previously been shown to be more effective than targeting one gene alone. In this study, we sought to determine if targeting Requiem and Alg-2 was more effective than targeting Requiem alone. We found that targeting Requiem and Alg-2 did not result in extended culture viability, but resulted in an increase in maximum viable cell numbers and cumulative IVCD under fed-batch conditions. This in turn led to an approximately 1.5-fold increase in recombinant protein productivity. PMID- 20571938 TI - Taking evolution seriously in political science. AB - In this essay, we explore the epistemological and ontological assumptions that have been made to make political science "scientific." We show how political science has generally adopted an ontologically reductionist philosophy of science derived from Newtonian physics and mechanics. This mechanical framework has encountered problems and constraints on its explanatory power, because an emphasis on equilibrium analysis is ill-suited for the study of political change. We outline the primary differences between an evolutionary ontology of social science and the physics-based philosophy commonly employed. Finally, we show how evolutionary thinking adds insight into the study of political phenomena and research questions that are of central importance to the field, such as preference formation. PMID- 20571939 TI - Uncertainty as a fundamental scientific value. AB - The author argues that, though social scientists generally value tolerance for ambiguity, and some even assert a fundamental indeterminacy in human systems, there is still a discipline-wide discomfort with uncertainty and ambiguity. It is argued that this distaste for uncertainty derives from a distorted view of the classical physical sciences, a view that ignores the essentially critical and radical foundations of scientific practice. The drive for certainty, it is argued, is essentially unscientific, in that certain, or adequate, forms of knowledge can only recapitulate the already known and in their dogmatic and institutionalized forms prevent the development of genuinely new knowledge. In contrast, uncertainty is defended as a positive condition, generative of new knowledge because it is open to discovery and to the mystery of the other. The conclusion drawn from this analysis is that the social sciences can only progress if uncertainty, or mystery, is protected and cultivated through a scientific discourse constituted in local and concrete terms (rather than in general and universal ones) and through a self-reflective and self-critical research praxis. PMID- 20571940 TI - Role of tumor suppressor and angiogenesis markers in prediction of recurrence of non muscle invasive bladder cancer. AB - Non muscle invasive bladder cancers recur frequently and identification of biomarkers for predicting recurrence are necessary. The present study evaluated the individual and synergistic effects of tumor suppressor (p53/p21waf1) and angiogenesis [vascular endothelial growth factor (VEGF)/endoglin (CD105)] markers. The study included 90 cases of non muscle invasive bladder cancer. Cell spots were stained with primary antibodies and Flourescein isothiocyanate (FITC). Slides were observed under confocal laser scanning microscope for protein expression. The association between the markers individually and synergistically with recurrence were assessed by a chi2 and Fisher's Exact test. Survival analysis was performed to predict recurrence and test for significant difference in recurrence free survival probability. Recurrence [overall:39(43.3%) and low grade(LG):26(54.2%)] was significant with p53 and VEGF expression and the profiles p53/VEGF, p53/CD105, VEGF/CD105, p53/p21/CD105, p53/VEGF/CD105 and all four were significantly associated with recurrence in both groups. In the multivariable model the [HR(95%CI),p: overall and LG] profiles p21/VEGF [2.195(1.052-4.582),0.036; 3.425(1.332-8.811),0.011], VEGF/CD105[2.624(1.274 5.403),0.009 and 3.380(1.348-8.472),0.009], p53/p21/CD105 [2.000(0.993 4.027),0.052 and 2.539(1.047-6.157),0.039], p53/VEGF/CD105 [2.360(1.148 4.849),0.020 and 2.738(1.104-6.788),0.030], p21/VEGF/CD105 [2.611(1.189 5.731),0.017 and 3.946(1.530-10.182),0.005] and all four [2.382(1.021 5.556),0.045 and 3.572(1.287-9.911),0.014] significantly predicted the recurrence along with significant log rank. In the pTa subset (n = 33) the profiles p53/p21, p53/CD105, p21/VEGF, VEGF/CD105, p53/VEGF/CD105, p53/p21/CD105 and p21/VEGF/CD105, significantly predicted hazard for recurrence. The present study emphasizes an underlying association between tumor suppressor (p21waf1) and angiogenesis (VEGF/CD105) biomarkers. In addition combination profiles appeared to indicate an aggressive nature with high propensity for recurrence in LG and pTa tumours. PMID- 20571941 TI - Ten-year experiences on initial genetic examination in childhood acute lymphoblastic leukaemia in Hungary (1993-2002). Technical approaches and clinical implementation. AB - A nationwide study was started in 1993 to provide genetic diagnosis for all newly diagnosed childhood ALL cases in Hungary using cytogenetic examination, DNA-index determination, FISH (aneuploidy, ABL/BCR, TEL/AML1) and molecular genetic tests (ABL/BCR, MLL/AF4, TEL/AML1). Aim of the study was to assess the usefulness of different genetic methods, to study the frequency of various aberrations and their prognostic significance. Results were synthesized for genetic subgrouping of patients. To assess the prognostic value of genetic aberrations overall and event-free survival of genetic subgroups were compared using Kaplan-Meier method. Prognostic role of aberrations was investigated by multivariate analysis (Cox's regression) as well in comparison with other factors (age, sex, major congenital abnormalities, initial WBC, therapy, immunophenotype). Five hundred eighty-eight ALL cases were diagnosed between 1993-2002. Cytogenetic examination was performed in 537 (91%) (success rate 73%), DNA-index in 265 (45%), FISH in 74 (13%), TEL/AML1 RT-PCR in 219 (37%) cases producing genetic diagnosis in 457 patients (78%). Proportion of subgroups with good prognosis in prae-B-cell ALL was lower than expected: hyperdiploidB 18% (73/400), TEL/AML1+ 9% (36/400). Univariate analysis showed significantly better 5-year EFS in TEL/AML1+ (82%) and hyperdiploidB cases (78%) than in tetraploid (44%) or pseudodiploid (52%) subgroups. By multivariate analysis main negative prognostic factors were: congenital abnormalities, high WBC, delay in therapy, specific translocations. CONCLUSION: Complementary use of each of genetic methods used is necessary for reliable genetic diagnosis according to the algorithm presented. Specific genetic alterations proved to be of prognostic significance. PMID- 20571942 TI - Antimicrobial susceptibilities of coagulase-negative staphylococci (CNS) and streptococci from bovine subclinical mastitis cases. AB - The prevalence and antimicrobial susceptibilities of Staphylococci and Streptococci were assessed from subclinical mastitis cases. One hundred Coagulase Negative Staphylococci (CNS) and 34 Streptococci were identified. The most frequently isolated species were Staphylococcus haemolyticus (27%) and Staphylococcus simulans (24%). Susceptible CNS species revealed the highest resistance to penicillin G (58%), ampicillin (48%), neomycin (20%), and oleandomycin (14%). CNS methicillin resistance rates within 82 isolates were 21.95% and 1.22% by disk diffusion and PCR methods, respectively. These results suggested the disk diffusion method was more prone to yield false positives. Partial sequencing of the 16S rRNA region from the mecA carrying isolate (S. haemolyticus) was homologous with S. haemolyticus sequences/accessions obtained from GenBank. However, the mecA gene sequence from this isolate was more closely allied with the S. aureus mecA gene of human origins. Identical sequence data was acquired from the National Center for Biotechnology Information (NCBI) database, suggesting horizontal gene transfer between the two species. CNS beta-lactamase activity within 81 isolates was 29.63%. The most frequently isolated Streptococcus species were S. uberis (52%) and S. agalactiae (15%). Oleandomycin was the least effective antimicrobial agent on these isolates with 59% susceptibility. Results indicated that CNS and Streptococci exhibited various antimicrobial resistance responses. Consequently, isolation and identification of udder pathogens in herds suffering from subclinical agents is essential to select the most effective antimicrobial agent. Moreover, multiple resistance features of methicillin resistant (MR) isolates should be considered during antimicrobial susceptibility tests. PMID- 20571943 TI - Isolation, characterization, and abundance of filamentous members of Caldilineae in activated sludge. AB - Chloroflexi are currently believed to serve as backbone forming agents in the activated sludge of wastewater treatment plants (WWTPs). In this study, we isolated and characterized filamentous bacteria in the class Caldilineae of the phylum Chloroflexi in municipal WWTPs. Diversity analysis using Chloroflexi specific 16S rRNA gene clone libraries showed that 97% of the clones belonged to the subdivision Anaerolineae comprising the two classes Anaerolineae (95%) and Caldilineae (2%). Clones of Caldilineae were related to a thermophilic filament Caldilinea aerophila with 93% 16S rRNA gene sequence similarity. We obtained filamentous isolates classified into the class Caldilineae showing the best match to C. aerophila with 89% 16S rRNA gene sequence similarity. Isolates showed no ability to assimilate glucose or N-acetylglucosamine or to degrade biopolymers which were observed in filamentous Chloroflexi of WWTPs. The assessment of relative abundance based on quantitative PCR of the 16S rRNA gene indicated that members of the class Caldilineae comprised 12-19% of the Chloroflexi in the activated sludge. Additionally, fluorescence in situ hybridization experiments showed that diverse filamentous Caldilineae inhabit the activated sludge of municipal WWTPs. These findings yield insight into the role of filamentous mesophilic Caldilinea in stabilizing flocs of activated sludge in a wide range of WWTPs. PMID- 20571944 TI - Assessment of soil fungal communities using pyrosequencing. AB - Pyrosequencing, a non-electrophoretic method of DNA sequencing, was used to investigate the extensive fungal community in soils of three islands in the Yellow Sea of Korea, between Korea and China. Pyrosequencing was carried out on amplicons derived from the 5' region of 18S rDNA. A total of 10,166 reads were obtained, with an average length of 103 bp. The maximum number of fungal phylotypes in soil predicted at 99% similarity was 3,334. The maximum numbers of phylotypes predicted at 97% and 95% similarities were 736 and 286, respectively. Through phylogenetic assignment using BLASTN, a total of 372 tentative taxa were identified. The majority of true fungal sequences recovered in this study belonged to the Ascomycota (182 tentative taxa in 2,708 reads) and Basidiomycota (172 tentative taxa in 6,837 reads). The predominant species of Ascomycota detected have been described as lichen-forming fungi, litter/wood decomposers, plant parasites, endophytes, and saprotrophs: Peltigera neopolydactyla (Lecanoromycetes), Paecilomyces sp. (Sordariomycetes), Phacopsis huuskonenii (Lecanoromycetes), and Raffaelea hennebertii (mitosporicAscomycota). The majority of sequences in the Basidiomycota matched ectomycorrhizal and wood rotting fungi, including species of the Agaricales and Aphyllophorales, respectively. A high number of sequences in the Thelephorales, Boletales, Stereales, Hymenochaetales, and Ceratobasidiomycetes were also detected. By applying high-throughput pyrosequencing, we observed a high diversity of soil fungi and found evidence that pyrosequencing is a reliable technique for investigating fungal communities in soils. PMID- 20571945 TI - Kinetic evaluation of products inhibition to succinic acid producers Escherichia coli NZN111, AFP111, BL21, and Actinobacillus succinogenes 130Z T. AB - Succinic acid is one of the platform compounds and its production via natural feedstocks has drawn worldwide concerns. To evaluate the inhibitory effects of fermentation products on the growth of Actinobacillus succinogenes 130Z(T) and Escherichia coli NZN111, AFP111, BL21, fermentations with addition of individual products in medium were carried out. The cell growth was inhibited when the concentrations of formate, acetate, lactate, and succinate were at range of 8.8 17.6 g/L, 10-40 g/L, 9-18 g/L, and 10-80 g/L, respectively. For these two species of bacteria, E. coli was more resistant to acid products than A. succinogenes, while both endured succinate rather than by-products. As a result of end product inhibition, succinate production yield by A. succinogenes decreased from 1.11 to 0.49 g/g glucose. Logistic and Monod mathematical models were presented to simulate the inhibition kinetics. The Logistic model was found more suitable for describing the overall synergistic inhibitory effects. PMID- 20571947 TI - Gaetbulibacter jejuensis sp. nov., isolated from seawater. AB - A novel marine bacterium, designated strain CNURIC014(T) was isolated from coastal seawater of Jeju Island in Korea. Strain CNURIC014(T) formed yellow colonies on marine agar 2216 and the cells were Gram-negative, non-motile, strictly aerobic, rod-shaped. The temperature, pH and NaCl ranges for growth were 15-37 degrees C, pH 6.0-9.0 and 1.0-7.0% NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CNURIC014(T) was most closely related to Gaetbulibacter marinus and Gaetbulibacter saemankumensis, with a sequence similarity of 95.1% and 94.6%, respectively. The DNA G+C content of the strain was 33.1 mol% and the major respiratory quinone was menaquinone-6. The major cellular fatty acids were iso-C(15:1) (22.8%), iso-C(15:0) (18.8%), summed feature 3 (iso-C(15:0) 2-OH/C(16:1) omega 7c, 12.9%) and iso-C(17:0) 3-OH (11.5%). On the basis of phenotypic, phylogenetic, and genotypic data, strain CNURIC014(T) represents a novel species within the genus Geatbulibacter, for which the name Gaetbulibacter jejuensis sp. nov. is proposed. The type strain is CNURIC014(T)(=KCTC 22615(T) =JCM 15976(T)). PMID- 20571946 TI - Characterization of cultivated fungi isolated from grape marc wastes through the use of amplified rDNA restriction analysis and sequencing. AB - Microbial assessment of grape marc wastes, the residual solid by-product of the wine-industry, was performed by identifying phylogenetically the fungal culturable diversity in order to evaluate environmental and disposal safety issues and to discuss ecological considerations of applications on agricultural land. Fungal spores in grape marc were estimated to 4.7 x 10(6) per g dry weight. Fifty six fungal isolates were classified into eight operational taxonomic units (OTUs) following amplified ribosomal DNA restriction analysis (ARDRA) and colony morphology. Based on 18S rRNA gene and 5.8S rRNA gene-ITS sequencing, the isolates representing OTUs #1, #2, #3, and #4, which comprised 44.6%, 26.8%, 12.5%, and 5.3%, respectively, of the number of the total isolates, were identified as Aspergillus fumigatus, Bionectria ochroleuca, Haematonectria haematococca, and Trichosporon mycotoxinivorans. The isolates of OTU#5 demonstrated high phylogenetic affinity with Penicillium spp., while members of OTUs #6 and #7 were closer linked with Geotrichum candidum var. citri-aurantii and Mycocladus corymbifer, respectively (95.4 and 97.9% similarities in respect to their 5.8S rRNA gene-ITS sequences). The OTU#8 with a single isolate was related with Aspergillus strains. It appears that most of the fungal isolates are associated with the initial raw material. Despite the fact that some of the species identified may potentially act as pathogens, measures such as the avoidance of maintaining large and unprocessed quantities of grape marc wastes in premises without adequate aeration, together with its suitable biological treatment (e.g., composting) prior to any agriculture-related application, could eliminate any pertinent health risks. PMID- 20571948 TI - Oceanobacillus manasiensis sp. nov., a moderately halophilic bacterium isolated from the salt lakes of Xinjiang, China. AB - Three Gram reaction positive, rod-shaped, moderately motile halophilic bacterial strains, designated YD3-56(T), YD16, and YH29, were isolated from the sediments of Manasi and Aiding salt lakes in the Xinjiang region of China, respectively. The strains grew optimally at 30-37 degrees C, pH 8-11, in the presence of 5-10% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strains were closely related to members of the genus Oceanobacillus, exhibiting 99.1-99.2% similarity to O. kapialis KCTC 13177(T), 99.2-99.3% to O. picturae KCTC 3821(T), and 94.2-96% sequence similarity to other described Oceanobacillus species. SDS-PAGE of whole cell proteins preparations demonstrated that the strains exhibited high similarity to each other, but distinguished from O. kapialis KCTC 13177(T) and O. picturae KCTC 3821(T) (75%). DNA-DNA hybridization revealed that the similarity between the representative strain YD3 56(T) and O. kapialis KCTC 13177(T) was 35.3%, and the similarity between YD3 56(T) and O. picturae KCTC 3821(T) was 22.3%. Chemotaxonomic analysis of the strains showed menaquinone-7 was the predominant respiratory quinine. Major cellular fatty acids were anteiso-C(15:0) and anteiso-C(17:0). The polar lipid pattern for strain YD3-56(T) predominantly contained phosphatidylcholine, and trace to moderate amounts of phosphatidyl ethanolamine and hydroxy-phosphatidyl ethanolamine. The diamino acid in murein was meso-diaminopimelic acid. The DNA G+C content of the strains was 39.7-40.1 mol%. On the basis of these results, the three strains should be classified as a novel species of the genus Oceanobacillus, for which the name Oceanobacillus manasiensis sp. nov. has been proposed, with the type strain as YD3-56(T) (=CGMCC 1.9105(T) =NBRC 105903(T)). PMID- 20571949 TI - Cel8H, a novel endoglucanase from the halophilic bacterium Halomonas sp. S66-4: molecular cloning, heterogonous expression, and biochemical characterization. AB - A recombinant Escherichia coli clone expressing an endoglucanase was identified from a genomic library of the halophilic bacterium Halomonas sp. S66-4, and the enzyme was designated Cel8H. The cel8H gene consisted of 1,053 bp and encoded 350 amino acids sharing the highest identity of 48% to other known endoglucanases. The protein was expressed in E. coli BL21 (DE3) and purified to homogeneity. The purified recombinant enzyme had an optimal activity of 4.9 U/mg at pH 5 and 45 degrees C toward the substrate carboxymethylcellulose. It exhibited extraordinary properties which differed from endoglucanases reported previously at the point of high salt tolerance above 5 M, simultaneously with high pH stability at pH 4-12 and high temperature stability at 40-60 degrees C. Various substrate tests indicated that the enzyme hydrolyzes beta-1,4-glucosidic bonds specifically. PMID- 20571950 TI - Identification and characterization of a novel bacterial ATP-sensitive K+ channel. AB - Five bacterial species that are most likely to have putative prokaryotic inward rectifier K(+) (Kir) channels were selected by in silico sequence homology and membrane topology analyses with respect to the number of transmembrane domains (TMs) and the presence of K(+) selectivity filter and/or ATP binding sites in reference to rabbit heart inward rectifier K(+) channel (Kir6.2). A dot blot assay with genomic DNAs when probed with whole rabbit Kir6.2 cDNA further supported the in silico analysis by exhibiting a stronger hybridization in species with putative Kir's compared to one without a Kir. Among them, Chromobacterium violaceum gave rise to a putative Kir channel gene, which was PCR cloned into the bacterial expression vector pET30b(+), and its expression was induced in Escherichia coli and confirmed by gel purification and immunoblotting. On the other hand, this putative bacterial Kir channel was functionally expressed in Xenopus oocytes and its channel activity was measured electrophysiologically by using two electrode voltage clamping (TEVC). Results revealed a K(+) current with characteristics similar to those of the ATP-sensitive K(+) (K-ATP) channel. Collectively, cloning and functional characterization of bacterial ion channels could be greatly facilitated by combining the in silico analysis and heterologous expression in Xenopus oocytes. PMID- 20571951 TI - Production, partial characterization, and immobilization in alginate beads of an alkaline protease from a new thermophilic fungus Myceliophthora sp. AB - Thermophilic fungi produce thermostable enzymes which have a number of applications, mainly in biotechnological processes. In this work, we describe the characterization of a protease produced in solidstate (SSF) and submerged (SmF) fermentations by a newly isolated thermophilic fungus identified as a putative new species in the genus Myceliophthora. Enzyme-production rate was evaluated for both fermentation processes, and in SSF, using a medium composed of a mixture of wheat bran and casein, the proteolytic output was 4.5-fold larger than that obtained in SmF. Additionally, the peak of proteolytic activity was obtained after 3 days for SSF whereas for SmF it was after 4 days. The crude enzyme obtained by both SSF and SmF displayed similar optimum temperature at 50 degrees C, but the optimum pH shifted from 7 (SmF) to 9(SSF). The alkaline protease produced through solid-state fermentation (SSF), was immobilized on beads of calcium alginate, allowing comparative analyses of free and immobilized proteases to be carried out. It was observed that both optimum temperature and thermal stability of the immobilized enzyme were higher than for the free enzyme. Moreover, the immobilized enzyme showed considerable stability for up to 7 reuses. PMID- 20571952 TI - Altered protein expression patterns of Mycobacterium tuberculosis induced by ATB107. AB - ATB107 is a potent inhibitor of indole-3-glycerol phosphate synthase (IGPS). It can effectively inhibit the growth of clinical isolates of drug-resistant Mycobacterium tuberculosis strains as well as M. tuberculosis H37Rv. To investigate the mechanism of ATB107 action in M. tuberculosis, two-dimensional gel electrophoresis coupled with MALDI-TOF-MS analysis (2-DE-MS) was performed to illustrate alterations in the protein expression profile in response to ATB107. Results show that ATB107 affected tryptophan biosynthesis by decreasing the expression of protein encoded by Rv3246c, the transcriptional regulatory protein of MtrA belonging to the MtrA-MtrB two-component regulatory system, in both drug sensitive and drug-resistant virulent strains. ATB107 might present a stress condition similar to isoniazid (INH) or ethionamide for M. tuberculosis since the altered expression in response to ATB107 of some genes, such as Rv3140, Rv2243, and Rv2428, is consistent with INH or ethionamide treatment. After incubation with ATB107, the expression of 2 proteins encoded by Rv0685 and Rv2624c was down regulated while that of protein encoded by Rv3140 was up-regulated in all M. tuberculosis strains used in this study. This may be the common response to tryptophan absence; however, relations to ATB107 are unknown and further evaluation is warranted. PMID- 20571953 TI - Phenotypic diversity of Escherichia coli O157:H7 strains associated with the plasmid O157. AB - Escherichia coli O157:H7, a food-borne pathogen, causes hemorrhagic colitis and the hemolytic-uremic syndrome. A putative virulence factor of E. coli O157:H7 is a 60-MDa plasmid (pO157) found in 99% of all clinical isolates and many bovine derived strains. The well characterized E. coli O157:H7 Sakai strain (Sakai) and its pO157-cured derivative (Sakai-Cu) were compared for phenotypic differences. Sakai-Cu had enhanced survival in synthetic gastric fluid, did not colonize cattle as well as wild-type Sakai, and had unchanged growth rates and tolerance to salt and heat. These results are consistent with our previous findings with another E. coli O157:H7 disease outbreak isolate ATCC 43894 and its pO157-cured (43894-Cu). However, despite the essentially sequence identical pO157 in these strains, Sakai-Cu had changes in antibiotic susceptibility and motility that did not occur in the 43894-Cu strain. This unexpected result was systematically analyzed using phenotypic microarrays testing 1,920 conditions with Sakai, 43894, and the plasmid-cured mutants. The influence of the pO157 differed between strains on a wide number of growth/survival conditions. Relative expression of genes related to acid resistance (gadA, gadX, and rpoS) and flagella production (fliC and flhD) were tested using quantitative real-time PCR and gadA and rpoS expression differed between Sakai-Cu and 43894-Cu. The strain-specific differences in phenotype that resulted from the loss of essentially DNA-sequence identical pO157 were likely due to the chromosomal genetic diversity between strains. The O157:H7 serotype diversity was further highlighted by phenotypic microarray comparisons of the two outbreak strains with a genotype 6 bovine E. coli O157:H7 isolate, rarely associated with human disease. PMID- 20571954 TI - Genetic diversity of chromosomal metallo-beta-lactamase genes in clinical isolates of Elizabethkingia meningoseptica from Korea. AB - This study was performed to characterize the chromosomal metallo-beta-lactamases (MBLs) of Elizabethkingia meningoseptica isolated from Korea and to propose a clustering method of BlaB and GOB MBLs based on their amino acid similarities. Chromosomal MBL genes were amplified by PCR from 31 clinical isolates of E. meningoseptica. These PCR products were then cloned into a vector and electrotransformed into E. coli DH5 alpha. Nucleotide sequencing was performed by the dideoxy chain termination method using PCR products or cloned DNA fragments. Antimicrobial susceptibilities were determined by the agar dilution method. PCR experiments showed that all 31 E. meningoseptica isolates contained both the blaB and the bla (GOB) genes. DNA sequence analysis revealed that E. meningoseptica isolates possessed seven types of blaB gene, including five novel variants (blaB 9 to blaB-13) and 11 types of bla (GOB) gene, including 10 novel variants (bla (GOB-8) to bla (GOB-17)). The most common combination of MBL was BlaB-12 plus GOB 17 (n=19). Minimum inhibitory concentrations of imipenem and meropenem for the electrotransformants harboring novel BlaB and GOB MBLs were two- or four-fold higher than those for the recipient E. coli DH5 alpha. BlaB and GOB MBLs were grouped in three and six clusters including fifteen novel variants, respectively, based on amino acid similarities. PMID- 20571955 TI - Proteomic analysis of hyphae-specific proteins that are expressed differentially in cakem1/cakem1 mutant strains of Candida albicans. AB - The yeast-to-hyphal transition is a major virulence factor in the fungal pathogen Candida albicans. Mutations in the CaKEM1 gene, which encodes a 5'-3' exoribonuclease responsible for mRNA degradation, show a defect in hyphal growth. We applied two-dimensional gel electrophoresis to identify hyphae-specific proteins that have altered expressions in the presence of the cakem1 mutation. Eight proteins, Eno1, Eps1, Fba1, Imh3, Lpd1, Met6, Pdc11, and Tsa1 were upregulated during hyphal transition in wild-type but not in cakem1/cakem1 mutant cells. A second group of proteins, Idh1, Idh2, and Ssb1, showed increased levels of expression in cakem1/cakem1 mutant cells when compared to wild-type cells. Overexpression of Lpd1, a component of the pyruvate dehydrogenase complex, caused slight hyperfilamentation in a wild-type strain and suppressed the filamentation defect of the cakem1 mutation. The Ssb1 protein, which is a potential heat shock protein, and the Imh3 protein, which is a putative enzyme in GMP biosynthesis also showed the filamentation-associated phenotypes. PMID- 20571956 TI - Helicobacter pylori gamma-glutamyltranspeptidase induces cell cycle arrest at the G1-S phase transition. AB - In our previous study, we showed that Helicobacter pylori gamma glutamyltranspeptidase (GGT) is associated with H. pylori-induced apoptosis through a mitochondrial pathway. To better understand the role of GGT in apoptosis, we examined the effect of GGT on cell cycle regulation in AGS cells. To determine the effect of recombinant GGT (rGGT) on cell cycle distribution and apoptosis, rGGT-treated and untreated AGS cells were analyzed in parallel by flow cytometry using propidium iodide (PI). We found that rGGT inhibited the growth of AGS cells in a time-dependent manner, and that the pre-exposure of cells to a caspase-3 inhibitor (z-DEVD-fmk) effectively blocked GGT-induced apoptosis. Cell cycle analysis showed G1 phase arrest and apoptosis in AGS cells following rGGT treatment. The rGGT-mediated G1 phase arrest was found to be associated with down regulation of cyclin E, cyclin A, Cdk 4, and Cdk 6, and the up-regulation of the cyclin-dependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition. PMID- 20571958 TI - Acinetobacter baumannii outer membrane protein A induces dendritic cell death through mitochondrial targeting. AB - Acinetobacter baumannii outer membrane protein A (AbOmpA) is a potential virulence factor that induces epithelial cell death, but its pathologic effects on the immune system have yet to be determined. The present study investigated the pathologic events occurring in dendritic cells (DCs) exposed to a cytotoxic concentration of AbOmpA. AbOmpA induced early-onset apoptosis and delayed-onset necrosis in DCs. AbOmpA targeted the mitochondria and induced the production of reactive oxygen species (ROS). ROS were directly responsible for both apoptosis and necrosis of AbOmpA-treated DCs. These results demonstrate that the AbOmpA secreted from A. baumannii induces DC death, which may impair T cell biology to induce adaptive immune responses against A. baumannii. PMID- 20571957 TI - Helicobacter pylori apo-Fur regulation appears unconserved across species. AB - The Ferric Uptake Regulator (Fur) is a transcriptional regulator that is conserved across a broad number of bacterial species and has been shown to regulate expression of iron uptake and storage genes. Additionally, Fur has been shown to be an important colonization factor of the gastric pathogen Helicobacter pylori. In H. pylori, Fur-dependent regulation appears to be unique in that Fur is able to act as a transcriptional repressor when bound to iron as well as in its iron free (apo) form. To date, apo-regulation has not been identified in any other bacterium. To determine whether Fur from other species has the capacity for apo-regulation, we investigated the ability of Fur from Escherichia coli, Campylobacter jejuni, Desulfovibrio vulgaris Hildenborough, Pseudomonas aeruginosa, and Vibrio cholerae to complement both iron-bound and apo-Fur regulation within the context of a H. pylori fur mutant. We found that while some Fur species (E. coli, C. jejuni, and V. cholerae) complemented iron-bound regulation, apo-regulation was unable to be complemented by any of the examined species. These data suggest that despite the conservation among bacterial Fur proteins, H. pylori Fur contains unique structure/function features that make it novel in comparison to Fur from other species. PMID- 20571959 TI - Molecular cloning, purification, and characterization of a novel, acidic, pH stable endoglucanase from Martelella mediterranea. AB - A novel gene encoding an endoglucanase designated Cel5D was cloned from a marine bacterium Martelella mediterranea by genomic library. The gene had a 1,113 bp opening reading frame encoding a 371-amino-acid protein with a molecular mass of 40,508 Da and containing a putative signal peptide (41 amino acids). Cel5D had low similarity (48-51% identity) with other known endoglucanases and consisted of one single catalytic domain, which belonged to the glycosyl hydrolase family 5. The maximum activity of Cel5D was observed at 60 degrees C and pH 5.0. Cel5D displayed broad pH stability within the range of pH 3.0-11.0 and retained hydrolytic activity in the presence of a wide variety of metal ions and some chemical reagents. These characteristics suggest that the enzyme has considerable potential in industrial applications. PMID- 20571960 TI - Identification of genes that are dispensable for animal infection by Salmonella typhimurium. AB - In the current study, we generated a pool of Salmonella typhimurium mutants using the Tn10d-cam mini-transposon. This pool of mutants was administered to BALB/c mice through the oral route, and bacteria were recovered from the spleen 3 days post-infection. After three rounds of serial passage, we observed enrichment of two insertion mutants, a yddG insertion and an amyA insertion. These two genes have been implicated in growth on plant products (amyA) and survival in the presence of paraquat (yddG), both of which are natural environments for Salmonella. Thus, while in vivo expression technology has identified S. typhimurium genes that are absolutely necessary for animal infection, other genes involved in vegetative growth also appear to play role in the establishment of pathogenesis. PMID- 20571961 TI - Halomonas jeotgali sp. nov., a new moderate halophilic bacterium isolated from a traditional fermented seafood. AB - A moderate halophilic, Gram-negative, non-motile, rod-shape, and aerobe designated as strain Hwa(T) was isolated from traditional fermented Korean seafood, which presented as a single cell or paired cells. Optimal growth occurred at 25 degrees C in 10% (w/v) salts at pH 7.0-8.0; however, growth occurred in a temperature range of 10-32 degrees C, a salts concentration of 5 25% (w/v) and pH 5.0-10.0. Tests for oxidase and catalase were positive. The cells produced poly-beta-hydroxybutyric acid, but not exopolysaccharide. Based on the 16S rRNA gene sequence, not only was there low similarity between strain Hwa(T) and all other species (94.1% similarity with H. subglaciescola DSM 4683(T), 94.0% similarity with H. sulfidaeris Esulfide1(T), 93.6% similarity with H. cerina SP4(T) and 93.0% similarity with H. halodurans DSM 5160(T)), but the phylogenetic analysis revealed that the isolate may be classified as a novel species belonging to the genus Halomonas in the class Gammaproteobacteria. The predominant fatty acids of strain Hwa(T) were C(18:1) omega 7c, C(16:0), C(12:0) 3-OH and C(16:1) omega 7c/C(15:0) iso 2-OH. The DNA G+C content was calculated as 61.7 mol%. Based on phenotypic, genotypic, and phylogenetic characteristics, it is proposed that the strain designated as Hwa(T) be assigned to the genus Halomonas as Halomonas jeotgali sp. nov. (=KCTC 22487(T) =JCM 15645(T)). PMID- 20571962 TI - The relevance of intrinsic subtype to clinicopathological features and prognosis in 4,266 Japanese women with breast cancer. AB - BACKGROUND: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 expression status in breast cancer function as prognostic and predictive factors that enable individualized treatment. Intrinsic subtype classification has also been performed based on these and other biological and prognostic characteristics. However, clinical analysis of such subtypes in a large number of Japanese breast cancer patients has not yet been reported. METHODS: Between January 2003 and December 2007, 4,266 patients with primary breast cancer were registered. Four subtypes based on immunohistochemically evaluated ER/PgR/HER2 status, clinicopathological features, and prognosis were analyzed retrospectively. RESULTS: The following subtype distribution was observed: luminal A type (ER+ and/or PgR+, HER2-), 3,046 cases (71%); luminal B type (ER+ and/or PgR+, HER2+), 321 cases (8%); HER2 type (ER-, PgR-, HER2+), 398 cases (9%); and triple negative (TN) type (ER-, PgR-, HER2-), 501 cases (12%). The HER2+ subtypes (luminal B and HER2 types) had a significantly higher incidence of lymph node metastasis and lymphatic permeation, while the hormone receptor negative subtypes (HER2 and TN types) showed a significantly higher nuclear grade. Overall, patients with HER2-type and TN-type disease had a significantly poorer prognosis than other subtypes. CONCLUSION: Intrinsic breast cancer subtypes are associated with clinicopathological features and prognosis in Japanese women. Long-term clinical observation of the relationship between each subtype and therapies used should provide useful information for selecting appropriately tailored treatments. PMID- 20571963 TI - Effect of sulfite on antioxidant enzymes and lipid peroxidation in normal and sulfite oxidase-deficient rat erythrocytes. AB - Sulfite and related chemical such as sulfite salts and sulfur dioxide has been used as a preservative in food and drugs. This molecule has also been generated from the catabolism of sulfur-containing amino acids. Sulfite is a very reactive and potentially toxic molecule and has to be detoxified by the enzyme sulfite oxidase (SOX). The aim of this study was to investigate the effects of ingested sulfite on erythrocyte antioxidant status by measuring glucose-6-phosphate dehydrogenase (G-6-PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant status by measuring thiobarbituric acid reactive substances (TBARS) in normal and SOX-deficient rats. Rats were assigned to four groups (n = 10 rats/group) as follows; control (C), sulfite (CS), deficient (D), and deficient + sulfite (DS). SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten (W). Sulfite (25 mg/kg) was administered to the animals via their drinking water. At the end of 6 weeks, Erythrocyte G-6-PD, SOD, and GPx but not CAT activities were found to be significantly increased with and without sulfite treatment in SOX-deficient groups. Sulfite treatment alone was also significantly increased erythrocytes' SOD activity in CS group compared to control. TBARS levels were found to be significantly increased in CS and DS groups and decreased in D group. When SOX-deficient rats treated with sulfite, TBARS level was still higher than other groups. In conclusion, these results suggested that erythrocyte antioxidant capacity, a defense mechanism against the oxidative challenge, increased by endogenous and exogenous sulfite due to its oxidant nature. This increase was also observed in CS and DS groups but it was insufficient to prevent lipid peroxidation. PMID- 20571964 TI - Tempol protects the gallbladder against ischemia/reperfusion. AB - Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca(2+) influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury. PMID- 20571965 TI - [Japanese encephalitis: a fast-changing viral disease]. AB - The following aspects are dealt with in this article: 1) current geographical distribution of Japanese encephalitis; 2) clinical patterns of Japanese encephalitis; 3) vertebrate hosts of Japanese encephalitis virus; 4) vectors of JE virus; 5) epidemiological locations (endemic area, endemoepidemic area, epidemic area); 6) unknown epidemiological aspects; 7) JE virus serotypes; 8) evolution of the disease and recent epidemiological changes; 9) phylogenetic origin of the JE virus; 10) ecological changes in the past, factors in the emergence of the disease; and 11) the future: Can we predict how the situation will evolve? PMID- 20571966 TI - RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. AB - Lymph node (LN) metastasis is one of the most important adverse prognostic factors for pancreatic cancer. The aim of this study was to identify novel lymphatic metastasis-associated markers for pancreatic cancer. DNA microarray analysis was used to determine and compare the expression profiles of 17 pancreatic cancer tissues with LN metastasis and 17 pancreatic cancer tissues without LN metastasis. The microarray results were validated by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Only 58 genes were differentially expressed between the two groups with a difference in signal intensity ratio greater than a 1.5-fold change. Of these genes, 30 were significantly down-regulated in the LN metastasis group. Among five selected down regulated genes for validation using real-time PCR, the expression of DST, FosB, RGS16, and CXCL12 was significantly lower in the LN metastasis group. Immunohistochemical analysis confirmed RGS16 and FosB underexpression in pancreatic cancer tissues with LN metastasis. RGS16 and FosB underexpression was associated with poor patient survival. Our findings show that RGS16 and FosB are underexpressed in pancreatic cancer with lymph node metastasis and associated with reduced survival, suggesting that RGS16 and FosB might be prognostic markers for pancreatic cancer. PMID- 20571969 TI - Abstracts of ICAR 2010, Italian Conference on AIDS and Retroviruses. Brescia, Italy. June 20-22, 2010. PMID- 20571968 TI - Up-regulation of EphA2 and down-regulation of EphrinA1 are associated with the aggressive phenotype and poor prognosis of malignant glioma. AB - Malignant gliomas display over-expression of the receptor tyrosine kinase EphA2. However, expression levels of the EphA2 ligand, EphrinA1, have not been fully elucidated. Seventy-eight patients with primary gliomas were included in this study who underwent surgical resection, radiation, and chemotherapy. The expression of EphA2 and EphrinA1 in tumors was assessed by immunohistochemistry and was statistically analyzed in combination with the follow-up data of patients. EphA2 was highly expressed in most malignant gliomas, but EphrinA1 was expressed at low levels in these tumors. The increased EphA2 expression is associated with higher-grade histology and poor patient prognosis. Contrary to this, the increased EphrinA1 expression is associated with lower-grade histology, but not associated with poor patient prognosis. Moreover, patients with tumors positive for EphA2 and negative for EphrinA1 had significantly shorter overall and progression-free survival than patients with tumors positive for both EphA2 and EphrinA1, negative for both EphA2 and EphrinA1, or negative for EphA2 and positive for EphrinA1. RNAi-mediated suppression of endogenous EphA2 in human glioblastoma multiforme cells resulted in increased EphrinA1 levels, as well as decreased cell viability, anchorage independence and in vitro invasion, and increased apoptosis. Furthermore, suppression of EphA2 resulted in delayed tumor growth in mice xenografts. Together, these data indicate that up-regulation of EphA2 and down-regulation of Ephrina1 may correlate with poor prognosis for patients with high-grade glioma. EphA2 suppression partially reversed the aggressive phenotypes of malignant gliomas, possibly through up-regulating EphrinA1 expression, which may help explain how EphA2 modulates the malignant progression of gliomas. PMID- 20571967 TI - Hypermethylation of RARbeta2 correlates with high COX-2 expression and poor prognosis in patients with colorectal carcinoma. AB - Silencing of gene expression by aberrant methylation at the CpG islands is common in human tumors, including colorectal cancer. This epigenetic alteration affects promoter of genes having crucial cellular functions such as tumor suppressor, DNA repair, apoptosis, cell adhesion, etc. We investigated the methylation status in the promoter regions of the RARbeta2, RASSF1A, DAPKinase, and CDH1 genes in 73 colorectal carcinoma and 43 paired normal tissues of Tunisian patients using methylation-specific PCR assays. The association between methylation status and the clinicopathological features was evaluated. To determine whether aberrant methylation affects gene expression, we performed immunohistochemistry analysis for E-cadherin and COX-2, a target gene of RARbeta2. The methylation frequencies vary from 80.8% for RARbeta2 to 35.6% for RASSF1A while in non-tumor-paired samples; the frequencies of methylation are significantly lower for all the fourth genes tested. The methylation status did not correlate with any of the clinical features considered; however, aberrant methylation of RARbeta2 was associated with a shortened overall patients' survival (p log rank = 0.026); nevertheless, it needs to be confirmed on larger sample size. Moreover, a significant inverse association was observed between methylation status of RARbeta2 and COX-2 protein expression in tumor specimen (p = 0.014). On the other hand, we found that loss of E-cadherin expression was significantly associated with aberrant methylation of the CDH1 promoter (p = 0.005). Our findings showed that RARbeta2 was frequently methylated in colorectal cancer and correlated with a worse prognosis and high expression of COX-2 suggesting a link between these two proteins in colorectal carcinogenesis. We also showed that epigenetic alteration of CDH1 is a major mechanism of the loss of E-cadherin protein expression in primary colorectal tumors. PMID- 20571970 TI - Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials. AB - The limited effect of AChE inhibitors and NMDA receptor antagonists for the treatment of the cognitive symptoms of Alzheimer's disease has prompted the search for new drugs that are capable not only of treating behavioral symptoms, but also of modifying the disease process. Considerable research efforts have been focused on orthosteric muscarinic M1 functional agonists during the past decade to address both these strategies. Part of this research has included the use of non-human primates as models of cognitive impairment to demonstrate preclinical efficacy. No M1 functional agonist has been successfully registered for the treatment of Alzheimer's disease, mostly because of mechanism-related adverse side effects and marginal cognitive effects. However, the M1 agonist xanomeline exhibited preclinical and clinical efficacy for the treatment of the negative and cognitive symptoms of schizophrenia. These results prompted renewed interest in repositioning compounds such as sabcomeline (Proximagen Group plc) for this indication, as well as developing allosteric muscarinic M1 ligands to improve efficacy while reducing side-effect-related attrition. This review discusses preclinical and clinical data from orthosteric M1 functional agonists, focusing on target validation in primate cognition studies, and provides recommendations for testing a new generation of M1 ligands and compounds with novel mechanisms of action. PMID- 20571971 TI - The alpha2-delta protein: an auxiliary subunit of voltage-dependent calcium channels as a recognized drug target. AB - Currently, there are two drugs on the market, gabapentin (Neurontin) and pregabalin (Lyrica), that are proposed to exert their therapeutic effect through binding to the alpha2-delta subunit of voltage-sensitive calcium channels. This activity was unexpected, as the alpha2-delta subunit had previously been considered not to be a pharmacological target. In this review, the role of the alpha2-delta subunits is discussed and the mechanism of action of the alpha2 delta ligands in vitro and in vivo is summarized. Finally, new insights into the mechanism of drugs that bind to this protein are discussed. PMID- 20571973 TI - Circadian rhythm dysregulation in bipolar disorder. AB - When circadian rhythms - the daily oscillations of various physiological and behavioral events that are controlled by a central timekeeping mechanism - become desynchronized with the prevailing light:dark cycle, a maladaptative response can result. Animal data based primarily on genetic manipulations and clinical data from biomarker and gene expression studies support the notion that circadian abnormalities underlie certain psychiatric disorders. In particular, bipolar disorder has an interesting link to rhythm-related disease biology; other mood disturbances, such as major depressive disorder, seasonal affective disorder and the agitation and aggression accompanying severe dementia (sundowning), are also linked to changes in circadian rhythm function. Possibilities for pharmacological intervention derive most readily from the molecular oscillator, the cellular machinery that drives daily rhythms. PMID- 20571974 TI - Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder, the cause of which remains elusive. Neuroinflammation appears to be a ubiquitous pathological change in both patients and experimental models of PD, both of which present with the classical features of inflammation, but with evidence that the process has become uncontrolled. Therefore, the use of anti-inflammatory drugs in the treatment of PD appears to be a logical development. Preclinical studies have largely supported the potential of anti-inflammatory compounds in PD. However, reports are conflicting, and preclinical success with these compounds is generally achieved by administration prior to or at the same time as a neurotoxic insult. This regimen, therefore, fails to account for the fact that the disease process is well developed upon diagnosis in patients. Perhaps unsurprisingly, success in the clinic with anti-inflammatory PD compounds has been modest. It has been suggested that anti-inflammatory drugs may be useful as adjuncts to other therapeutic avenues, particularly drugs that aim to restore neuronal loss. Such an approach seems logical given that the etiology of PD is unlikely to arise from a single factor and, accordingly, treatment may require intervention at different mechanistic loci. This review discusses the anti-inflammatory agents that have been suggested to have potential for the treatment of PD. PMID- 20571972 TI - Using NMR approaches to drive the search for new CNS therapeutics. AB - The use of MRI-based imaging in drug development has received increased interest recently because of the difficulties associated with the development of CNS pharmacotherapies. While not yet routine, there have been significant advances in imaging that allow this technology to be used for evaluating disease state and drug effects. For disease states, both single and longitudinal studies of non invasive measures may be obtained to provide a read-out of disease processes and, potentially, to predict the disease state and its evolution. In addition, imaging has enabled the development of improved preclinical disease models based on changes in brain circuitry. Pharmacological MRI, the imaging-based evaluation of drug effects, includes measures of direct effects on the brain, as well as the effects of chronic dosing on brain changes and neurochemical changes associated with these brain effects using magnetic resonance spectroscopy. Thus, imaging may become an integrated process in drug development, during both the preclinical and clinical stages. However, validation, the implementation of good clinical practices and regulatory acceptance are hurdles that remain to be overcome. PMID- 20571975 TI - The use of mechanistic biomarkers for evaluating investigational CNS compounds in early drug development. AB - Biomarkers serve as the fundamental building blocks of modern translational research strategies, and are widely implemented in current drug development. Biomarker techniques range from simple biofluid biochemical endpoints to more complex assessments, including imaging. Although biomarker usage is common throughout drug development, applications may vary depending on whether a drug candidate is in early- or late-stage testing. In early clinical drug development, biomarkers capable of providing proof of mechanism are considered critical tools in the management of attrition during phase II clinical trials. For CNS drugs, the ability to unequivocally demonstrate pharmacologically driven biological activity in the brain, as a result of the interaction of a drug with its intended target, ensures that proof-of-concept trials are designed in a manner that adequately tests the clinical efficacy hypothesis and that patients are not being exposed to inactive drugs. This review focuses on recent advances in proof-of pharmacology biomarkers, with an emphasis on biochemical measures and simple circuit platforms used to demonstrate target engagement in central compartments. PMID- 20571976 TI - The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. AB - Serotonin 5-HT1A receptors are attractive targets for the development of improved antipsychotics. Indeed, extensive evidence in rodent models indicates that the activation of these receptors prevents extrapyramidal symptoms (EPS) induced by dopamine D2 receptor blockade, favors dopaminergic neurotransmission in the frontal cortex, has a positive influence on mood, and opposes NMDA receptor antagonist-induced cognitive and social interaction deficits. Therefore, 'third generation' antipsychotics that combine partial agonism at 5-HT1A receptors with antagonism (or partial agonism) at D2 receptors have been investigated, including aripiprazole, perospirone, lurasidone (Dainippon Sumitomo Pharma Co Ltd), cariprazine (Gedeon Richter Ltd/Forest Laboratories Inc/Mitsubishi Tanabe Pharma Corp), PF-217830 (Pfizer Inc), F-97013-GD, F-15063 and bifeprunox. Such compounds appear to provide therapeutic benefits against a broader range of symptoms of schizophrenia, including negative symptoms and cognitive deficits that are poorly controlled by established antipsychotics. Recently developed compounds are essentially free of EPS liability, and exhibit little or no interaction at sites that are potentially involved in causing side effects such as weight gain, metabolic disorders or autonomic disturbance. These compounds differ in their balance of 5-HT1A/D2 receptor affinity and agonist or antagonist properties; such differences are likely to translate into distinct therapeutic profiles. The balance of 5-HT1A/D2 receptor properties should therefore be considered when selecting compounds as antipsychotic development candidates. PMID- 20571977 TI - NLX-P101, an adeno-associated virus gene therapy encoding glutamic acid decarboxylase, for the potential treatment of Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative disease affecting nigrostriatal dopaminergic neurons. Dopamine depletion in the striatum leads to functional changes in several deep brain nuclei, including the subthalamic nucleus (STN), which becomes disinhibited and perturbs the control of body movement. Although there is no cure for PD, some pharmacological and surgical treatments can significantly improve the functional ability of patients, particularly in the early stages of the disease. Among neurodegenerative diseases, PD is a particularly suitable target for gene therapy because the neuropathology is largely confined to a relatively small region of the brain. Neurologix Inc is developing NLX-P101 (AAV2-GAD), an adeno-associated viral vector encoding glutamic acid decarboxylase (GAD), for the potential therapy of PD. As GAD potentiates inhibitory neurotransmission from the STN, sustained expression of GAD in the STN by direct delivery of NLX-P101 decreases STN overactivation. This procedure was demonstrated to be a safe and efficient method of reducing motor deficits in animal models of PD. A phase I clinical trial has demonstrated that NLX-P101 was safe and indicated the efficacy of this approach in patients with PD. Results from an ongoing phase II clinical trial of NLX-P101 are awaited to establish the clinical efficacy of this gene therapy. PMID- 20571978 TI - Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression. AB - Cariprazine (RGH-188), which is being codeveloped by Gedeon Richter Ltd, Forest Laboratories Inc and Mitsubishi Tanabe Pharma Corp, is a novel putative antipsychotic drug that exerts partial agonism at dopamine D2/D3 receptors, with preferential binding to D3 receptors, and partial agonism at serotonin 5-HT1A receptors. Its activity at D2/D3 receptors may be lower than that of the prototype partial agonist aripiprazole. The antipsychotic activity of cariprazine was demonstrated in animal models, and data also suggest that the propensity for extrapyramidal side effects is low and that the drug may have procognitive properties. Cariprazine is rapidly absorbed, with high oral bioavailability and a long plasma elimination t1/2. Cariprazine is in phase III clinical trials in patients with schizophrenia and in patients with bipolar disorder. Data from phase II trials in patients with schizophrenia and bipolar mania indicate that the drug has antipsychotic and antimanic properties that are superior to placebo. With its unique receptor affinity profile, cariprazine may represent a potential enrichment of the therapeutic armamentarium for schizophrenia and affective disorders. Its activity against the cognitive deficits associated with schizophrenia has to be carefully investigated. PMID- 20571979 TI - LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY 404039 for the potential treatment of schizophrenia. AB - LY-2140023 is a methionine amide prodrug of the orthosteric metabotropic glutamate receptor (mGluR)2/3 agonist LY-404039, being developed by Eli Lilly & Co, for the potential oral treatment of schizophrenia. LY-404039 is a rigid glutamate analog that selectively binds to mGluR2/3 compared with all other glutamate receptors and transporters, and with other monoaminergic receptors that have been implicated in the therapeutic efficacy of atypical antipsychotic drugs. Activation of mGluR2 has been associated with the antipsychotic-like behavioral effects of LY-404039, as indicated by experiments using mGluR2-/- and mGluR3-/- mice. Furthermore, mGluR2 acts as a glutamatergic autoreceptor in the brain regions that are believed to be important in the pathophysiology of schizophrenia, such as the prefrontal cortex, striatum, hippocampal formation and the thalamus. The antipsychotic efficacy of LY-2140023, predicted by a common battery of preclinical behavioral screens for antipsychotic drugs, was confirmed in a randomized, placebo-controlled, phase II clinical trial in patients with schizophrenia. In addition, LY-2140023 lacked the extrapyramidal and metabolic side effects that are commonly observed with the majority of currently approved antipsychotic drugs. Thus, LY-2140023 represents a rare psychiatric medicine that demonstrates the promise of being rationally developed from bench to bedside. PMID- 20571981 TI - First aid for failing flaps. AB - Wound coverage with pedicled (local, regional, or distant) or free flaps is commonplace throughout plastic surgery. However, irrespective of the method of tissue transfer or type of tissue being transferred, inflow and outflow remain key parameters for success. Much has been written detailing complex tissue transfers and delineating arterial and venous anatomy. Despite this, simple venous insufficiency causing venous congestion is common. In experimental models, when arterial inflow is impaired, even mild venous inadequacy affects flap survival. Furthermore, studies have shown that venous congestion is more detrimental to the rate and percentage of flap area surviving than arterial ischemia. Obviously, complete venous occlusion typically requires operative exploration and correction, but many instances occur when venous congestion occurs for reasons other than complete venous thrombosis. Here we detail the basic postoperative "first aid" techniques available to optimize venous drainage. Although these techniques are not a substitute for sound anatomic flap selection, good surgical technique, or re-operation when a significant underlying problem exists, they do offer additional options to improve flap outcomes. PMID- 20571980 TI - [Foreign dentures and dental tourism--willingness-to-pay and factors influencing the demand for foreign dental prosthesis in Germany]. AB - With the progressive realisation of the single European market, public interest has been directed towards cross-border healthcare services to an increasing extent. More and more dentures are being imported into Germany from foreign countries. Furthermore, patients are becoming ever more mobile, travelling to other countries to receive prosthetic treatment from dentists. The objective of this evaluation was to determine by means of a dedicated questionnaire the patients' individual preferences for foreign dentures and the potential savings. 1 368 individuals between the ages of 30 and 75 years were interviewed within a representative omnibus survey. The evaluation of the individual willingness-to pay included 4 treatment scenarios, which were assessed by the participants in a "bidding game". Participants could choose between a "crown scenario" and an "implant scenario", both with the subcategories "foreign dentures" and "dental tourism". The direct comparison revealed a preference for the "foreign dentures" option over "dental tourism". Average willingness-to-pay for the dental tourism option in the crown scenario was calculated as 80 Euro, and in the implant scenario as 280 Euro less in comparison with the willingness-to-pay for the foreign dentures option. The willingness to switch to a less expensive dentist was one of the main determinants in the causal explanation for the variance in willingness-to-pay. Quality proved to be the decisive criterion and was indicated by 92.4% participants. A lower price for dentures played a subordinate role and was only stated as the decisive factor by 31.1% participants. In conclusion, the results clearly indicate that the decision for or against foreign dentures and the extent of willingness-to-pay depends on a range of criteria, of which "price" is only one and not the decisive factor. PMID- 20571982 TI - The proximally designed sural flap based on the accompanying artery of the lesser saphenous vein. AB - Most of the literature about the sural flap deals with soft tissue defects at the lower leg and foot based on the classical description of Masquelet et al. Nevertheless, some authors have shown that the lesser saphenous vein and its accompanying artery play an important role in the vascularization of the posterior skin of the leg. This finding allowed a more proximal design of the flap, increasing its arc of rotation. Thirteen cases of distally based sural flaps were performed and divided in two groups according to the level where the flaps were harvested. In group A, the entire flap was outlined distal to the midpoint of the leg, and in group B, the flap was outlined proximal to the midpoint of the leg. In group A, all the soft tissue defects were located at the lower leg and the foot, and in group B, they involved the anterior the tibia. In group A, the complication rate was 33.33% and the flap survival rate was 83.33%. In group B, the complication rate was 42.85% and survival rate was 100%. The proximally designed sural flap can safely reach the anterior aspect of the tibia in its middle and distal thirds. PMID- 20571983 TI - Metachromatic leukodystrophy--an update. AB - Metachromatic leukodystrophy (MLD) is a rare lysosomal sphingolipid storage disorder, caused by a deficiency of arylsulfatase A (ASA). It is inherited in an autosomal recessive way, among Caucasians three causing alleles are frequent. Demyelination is the hallmark of MLD. Interest in the disease has increased as therapeutic options such as stem cell transplantation, enzyme replacement and gene therapy are topics of current research. A late-infantile (onset before 3 years of age), a juvenile form (onset before 16 years) and an adult form are usually distinguished. Rapid motor decline is typical for the first and also the second forms, the second may be preceded by cognitive and behavioural problems, which mainly characterize the adult form. There is evidence for a genotype phenotype correlation: patients homozygous for alleles which do not allow the expression of any enzyme activity (null-allele) suffer from the late infantile form; heterozygosity for a null allele and a non-null allele are more associated with the juvenile form and homozygosity for non-null alleles is more frequent in the most attenuated adult onset form. PMID- 20571984 TI - Association of cutaneous red-to-purple hemangiomas with leptomeningeal hemangiomas. a clinical study of two patients. AB - Cutaneous hemangioma is a benign vascular tumor of infancy with an initial proliferating period that appears between 1 to 2 weeks of life, extends during 18 months to 2 years of life, and then slowly regresses during several years until it disappears completely. They are characterized by endothelial cell proliferation followed by diminishing hyperplasia and progressive fibrosis. Vascular malformations are present at birth, grow commensurately with the child, and are characterized histologically by a normal rate of endothelial cell turnover, flat endothelium, thin (normal) basal membrane and normal mast cells. These cutaneous anomalies are commonly associated with cerebellar malformations, main cerebral arteries anomalies, congenital cardiac anomalies and/or coarctation of the aorta and persistence of embryonic arteries. Cutaneous hemangiomas can be associated with intracranial or extracranial hemangiomas that regress at the same time as the cutaneous hemangiomas. Cutaneous hemangiomas may show different types of color. Cutaneous red-to-purple hemangiomas are uncommon and their bright-red color is evident from the first weeks of life and remains unaltered until the hemangioma disappears. The intracranial angiographic studies in our series of more than 50 cases with facial hemangioma showed that patients with red-to-purple hemangiomas are commonly associated with localized leptomeningeal hemangiomas either in the ipsilateral or contralateral side. These leptomingeal hemangiomas were visualized only by MR enhanced with gadolinium. Involution of the cutaneous and leptomeningeal hemangiomas seems to occur simultaneously as in other types of external and internal hemangiomas. PMID- 20571985 TI - MR findings of the brain in children and adolescents with portal hypertension and the relationship with blood manganese levels. AB - BACKGROUND: Few studies have evaluated abnormalities on brain magnetic resonance imaging (MRI) in children and adolescents with chronic liver disease. AIMS: The aim of this study was to investigate the presence of T1 hyperintensity in the basal ganglia of pediatric patients with portal hypertension and its association with blood manganese levels. METHODS: A case control study of 22 patients with portal hypertension (14 Child-Pugh A cirrhosis, 8 non-cirrhotic portal hypertension) and 15 controls was conducted from 2006 to 2007. Blood manganese levels were measured using atomic absorption spectrophotometry. Brain MRI scans were performed using a 1.5 Tesla (Philips) scanner. RESULTS: Blood manganese levels were 26.01+/-12.82 microg/L for patients with portal hypertension (cirrhotic: 22.73+/-11.67 microg/L, non-cirrhotic: 32+/-13.32 microg/L) and 15.64+/-6.61 microg/L for controls (p=0.003). 14/22 patients with portal hypertension presented T1 hyperintensity in the basal ganglia [6/14 cirrhotic; 8/8 non-cirrhotic (p=0.018); zero controls (p=0.001)]. Mean blood manganese levels of patients with liver disease and normal vs. abnormal brain MRI scans were 18.45+/-8.38 microg/L and 30.47+/-13.07 microg/L, respectively (p=0.04). CONCLUSIONS: Brain MRI showed a high frequency (64%) of T1 hyperintensity in the basal ganglia of patients with portal hypertension, which correlated positively with blood manganese levels. This abnormality was found in 100% of the patients with portal hypertension and in 43% of those with mild cirrhotic disease. PMID- 20571986 TI - Chilblains as a diagnostic sign of aicardi-goutieres syndrome. AB - Aicardi-Goutieres syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease. PMID- 20571987 TI - Accuracy of three-dimensional photogrammetric images in non-synostotic cranial deformities. AB - OBJECTIVE: Given the increasing incidence of deformational plagiocephaly due to infants' supine sleeping position to prevent sudden infant death syndrome, reliable anthropometric diagnostics are needed. Besides the traditional method of measuring landmarks with callipers, three-dimensional (3D) photography has great potential. In this investigation the accuracy of 3D photogrammetry is studied. METHODS: The study included 100 randomly chosen children between the ages of 4 and 20 months with a non-synostotic cranial deformity in a retrospective analysis. Measurements of diagonals A and B on the infant's head were obtained once using callipers. 3D photographs of these children were measured 5 times by 5 clinicians separately. RESULTS: The inter- and intra-rater agreements of the 3D measurements had low variability in the variance component analysis. The standard deviations for reproducibility and repeatability were 0.117-0.283 cm for diagonals A and B. The intra-class correlation coefficients for the inter-rater reliability resulted in excellent agreement (0.97 for plagiocephaly, 0.98 for brachycephaly, 0.96 for combined deformity). The comparison of the 3D photographic and callipers measurements showed that 3D photography resulted in a slight over-estimation. CONCLUSION: 3D photogrammetry is potentially a reliable tool for treatment planning and follow-up of abnormal head shapes in infancy. PMID- 20571988 TI - Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect. AB - Mitochondrial NADH: ubiquinone oxidoreductase (complex I) deficiency accounts for most defects in mitochondrial oxidative phosphorylation. Pathogenic mutations have been described in all 7 mitochondrial and 12 of the 38 nuclear encoded subunits as well as in assembly factors by interfering with the building of the mature enzyme complex within the inner mitochondrial membrane. We now describe a male patient with a novel homozygous stop mutation in the NDUFAF2 gene. The boy presented with severe apnoea and nystagmus. MRI showed brainstem lesions without involvement of basal ganglia and thalamus, plasma lactate was normal or close to normal. He died after a fulminate course within 2 months after the first crisis. Neuropathology verified Leigh disease. We give a synopsis with other reported patients. Within the clinical spectrum of Leigh disease, patients with mutations in NDUFAF2 present with a distinct clinical pattern with predominantly brainstem involvement on MRI. The diagnosis should not be missed in spite of the normal lactate and lack of thalamus and basal ganglia changes on brain MRI. PMID- 20571989 TI - Cognitive profile in spastic paraplegia with thin corpus callosum and mutations in SPG11. AB - Autosomal recessive hereditary spastic paraplegia with thinning of the anterior corpus callosum (ARHSP-TCC) due to mutations in SPG11 on chromosome 15q (MIM610844) is the single most common cause of ARHSP. It is characterized by slowly progressive paraparesis and peripheral neuropathy. Although cognitive impairment, sometimes diagnosed as mental retardation, is an almost invariable feature, the extent and specific neuropsychological features are not fully understood. We report a comprehensive neuropsychological assessment in two ARHSP TCC patients harbouring mutations in SPG11. A specific impairment in executive functions occurring even before cognitive decline, may be considered the core of the neuropsychological profile of patients harbouring mutations in SPG11. PMID- 20571990 TI - The cytokine and chemokine profiles in rhabdomyolysis in a patient with Gaucher disease type II. AB - This report describes a patient with Gaucher disease type II who developed severe rhabdomyolysis. We treated him successfully and measured various cytokine and chemokine levels sequentially to elucidate the pathophysiology of rhabdomyolysis. The serum levels of interleukin-6, -8, -10, granulocyte colony-stimulating factor, interferon-gamma, and monocyte chemoattractant protein-1 were markedly elevated in the early phase of rhabdomyolysis. These findings indicate that cytokines and chemokines are related to the massive myolysis and regenerating process. A viral infection may have triggered rhabdomyolysis through exaggerated activation of macrophages in our patient. The profiles of cytokines and chemokines should be examined in further cases to increase our understanding of the pathophysiology of rhabdomyolysis. PMID- 20571992 TI - Two new boards for the next decade. PMID- 20571991 TI - Familial reducing body myopathy with cytoplasmic bodies and rigid spine revisited: identification of a second LIM domain mutation in FHL1. AB - OBJECTIVE: Reducing body myopathy (RBM) is a rare progressive disorder of muscle characterized by intracytoplasmic inclusions, which stain strongly with menadione NBT (nitroblue tetrazolium). We recently identified the four and a half LIM domain gene FHL1 located on chromosome Xq26 as the causative gene for RBM. So far eight familial cases and 21 sporadic patients with RBM have been reported in the literature. METHODS: We ascertained a total of 8 members of a German family initially reported by Goebel et al. as a mixed myopathy with rigid spine myopathy and reducing as well as cytoplasmic bodies. Clinical findings in the original and additional family members have been reviewed. Mutation detection was performed by direct sequencing of FHL1 exons. RESULTS: We identified a novel mutation (p.C150R) in the second LIM domain of FHL1 in six family members (1 male, 5 females). The male index patient was the most affected member presenting with rigid spine, followed by rapidly progressive muscle weakness. He died from the consequences of respiratory insufficiency at the age of 29.5 years. His sister, mother, grandmother, aunt and female cousin all carried the mutation in the heterozygous state. The sister is clinically unaffected; their mother had myopathic changes in her muscle biopsy, while the grandmother showed first signs of weakness at 50 years of age. The 54-year-old aunt and her daughter are clinically asymptomatic. CONCLUSION: We report a novel LIM2 domain mutation in FHL1 in a previously reported family with RBM with cytoplasmic bodies and spinal rigidity. While the male index patient was significantly affected, female carriers show varying manifestations and may be asymptomatic, likely reflecting varying degrees of X-inactivation. RBM continues to be associated with mutations in the LIM2 domain of FHL1. We also confirm our earlier observation that mutations at the N-terminal end of the LIM2 domain seem to be milder compared to mutations seen at the C-terminal part of the domain which cause severe disease even in female carriers. PMID- 20571993 TI - Improvement of mutism in a catatonic schizophrenia case by add-on treatment with amantadine. PMID- 20571994 TI - [Ear acupuncture points in neonates with neonatal abstinence syndrome due to maternal substitution therapy]. AB - BACKGROUND: This is a prospective observational study performed at a university teaching hospital. The aim of the study was to determine the presence and absence of acupuncture ear points in neonates with neonatal abstinence syndrome (NAS). PATIENTS AND METHOD: The patients are neonates with neonatal abstinence syndrome. The examination took place on the third day (mean value: 72.3 h) after delivery and was performed by a neuronal pen (PS 3 Silberbauer, Vienna, Austria). A integrated optical and sound signal detects the ear points that were assigned to the ear map. RESULTS: We investigate 5 neonates (3 males, 2 females, mean gestational age: 37+3, mean birth weight: 2,655 g). All investigated neonates showed the presence of active ear acupuncture points. The psychovegetative rim was the most common point in 100% of the children. In all neonates we found the presence of psychic ear points. The detectable psychic ear points are frustration point, R point and the psychotropic field nasal from the incisura intertragica. CONCLUSION: Ear points are detectable in neonates with NAS and do not depend on the side of the ear lobe. The most important point is the psychovegetative rim and, in all neonates with NAS, psychic ear points were detectable. So for the first time it is possible to identify psychic ear acupuncture points in neonates. In the future it could be possible to use active ear points in neonates for diagnostic and therapeutic options. PMID- 20571995 TI - [Acute intracranial haemorrhage during delivery--a case report]. AB - An acute intracranial haemorrhage during delivery or pregnancy is a rare complication and usually observed in connection with risk factors. We present the clinical course of a 32-year-old primigravida in the 40th week of gestation delivered in general anaesthesia by Caesarean section after premature rupture of the membranes and obstructed labour. Immediately after delivery and extubation, the patient appeared drowsy and with reduced consciousness. An emergency CCT presented an acute frontal haemorrhage with intraventricular bleeding. In this case there was no history of risk factors and no origin of the bleeding could be identified. A complete remission of the symptoms was achieved after ventricular drainage, intensive care support and consecutive rehabilitation. PMID- 20571996 TI - Tissue engineering and the use of stem/progenitor cells for airway epithelium repair. AB - Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a) a ductal cell type in the submucosal glands of the proximal trachea, (b) basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c) variant Clara cells (Clara v-cells) in the bronchioles and (d) at the junctions between the bronchioles and the alveolar ducts, and (e) alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a) embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, or amniotic fluid stem cells, (b) side population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c) fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema. PMID- 20571997 TI - [Extended spectrum beta lactamase forming bacteria--an increasing and serious problem in ambulatory medicine]. PMID- 20571998 TI - [Rash, fever, eosinophilia and elevated liver enzymes. DRESS syndrome (drug reaction or rash with eosinophilia and systemic symptoms)]. AB - We report on a patient with Pneumocystis jirovecii pneumonia who developed fever, rash, eosinophilia and hepatitis 10 days after initiation of a therapy with sulfamethoxazole and trimethoprim. A DRESS syndrome was diagnosed and the therapy was changed successfully to pyrimethamine and dapsone. We describe the clinical picture, causative drugs, pathogenesis, differential diagnoses and therapy of this life-threatening disease to acquaint the general practitioner with it. PMID- 20572000 TI - [A clinical approach in neuromuscular diseases in childhood]. AB - The group of neuromuscular disorders includes disorders of the motor neurons in the medulla oblongata and myelon, the peripheral nerves, the neuromuscular junction, and of the muscle. Clinical manifestation varies from pre-/perinatal to adulthood. The prevalence of all neuromuscular disorders is about 1:1500. In the last years, knowledge of genetic defects in neuromuscular disorders has dramatically increased. This is due to an increase in knowledge of the underlying genetic defects. Hence the classification of the neuromuscular disorders is still changing. In clinical practice the history and the clinical examination of patients with suspected NMDs is very important in the correct selection of the necessary investigations. Many investigations are possible, but should be chosen according to the patient's symptoms. Careful interpretation of the results most often defines diagnosis. The aim of this article is to establish a work-up according to the patient's symptoms and problems in childhood. PMID- 20571999 TI - [Polyneuropathies--short and sweet]. AB - Complaints of sensory loss and (painful) tingling in a stocking distribution are not uncommon in primary care. These symptoms are especially troublesome while getting asleep. Characteristically, ankle tendon reflexes and vibration perception are diminished. These are the hallmarks of distal-symmetric sensory polyneuropathy (PNP), with diabetes mellitus being the most common cause in our patient population. PNP presents itself only after years of suboptimal glycemic control in diabetes type 1. In patients with type 2, symptoms of PNP can precede formal diagnosis of diabetes! In this mini-review we present an algorithm for diagnosis and management of PNP's in general practice. PMID- 20572001 TI - [Stress incontinence in women]. PMID- 20572003 TI - [Monofilament test diagnose peripheral neuropathy]. PMID- 20572004 TI - [Carotid artery stenosis: the best surgical treatment is the dilatation-stent method ]. PMID- 20572002 TI - [Chronic right-sided pain-associated nondermatomal somatosensory deficit following an accident]. AB - We present the case of a 48-year old man who, eight years after an industrial accident, presents with chronic right-sided nondermatomal pain and hypaesthesia to heat and touch. During symmetric peripheral touch functional magnetic resonance imaging revealed hypometabolism in the left thalamus, somatosensory cortex, and anterior cingulate cortex. Pain-associated nondermatomal somatosensory deficits (NDSDs) localizing to one side of the body are a frequent clinical entity, which are often triggered by an accident. The tendency of NDSDs to extend to adjunct ipsilateral body parts and to become chronic points to maladaptive adjustment of pain-processing areas in the central nervous system. Psychological stress prior to or around the triggering event seems an important risk factor for NDSDs. PMID- 20572006 TI - [Physician sculpture puzzle]. PMID- 20572007 TI - [Physician art column]. PMID- 20572008 TI - Gr-1+CD11b+ myeloid-derived suppressor cells: formidable partners in tumor metastasis. AB - The growth and metastasis of solid tumors not only depends on their ability to escape from immune surveillance but also hinges on their ability to invade the vasculature system as well as to induce the formation of new blood vessels. Gr 1(+)CD11b(+) myeloid-derived suppressor cells (MDSCs), overproduced in tumor bearing hosts, contribute significantly to all these aspects. They also have a potential role in the osteolysis associated with bone metastases. They are formidable partners in tumor metastasis. PMID- 20572009 TI - Sin3a is required by sertoli cells to establish a niche for undifferentiated spermatogonia, germ cell tumors, and spermatid elongation. AB - Microenvironments support the maintenance of stem cells and the growth of tumors through largely unknown mechanisms. While cell-autonomous chromatin modifications have emerged as important determinants for self-renewal and differentiation of stem cells, a role for non-cell autonomous epigenetic contributions is not well established. Here, we genetically ablated the chromatin modifier Swi-independent 3a (Sin3a) in fetal Sertoli cells, which partly comprise the niche for male germline stem cells, and investigated its impact on spermatogenic cell fate and teratoma formation in vivo. Sertoli cell-specific Sin3a deletion resulted in the formation of few undifferentiated spermatogonia after birth while initially maintaining spermatogenic differentiation. Stem cell-associated markers Plzf, Gfra1, and Oct4 were downregulated in the mutant fetal gonad, while Sertoli cell markers Steel and Gdnf, which support germ cells, were not diminished. Following birth, markers of differentiating spermatogonia, Kit and Sohlh2, exhibited normal levels, but chemokine-signaling molecules chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF1) and chemokine (C-X-C motif) receptor 4 (CXCR4), expressed in Sertoli cells and germ cells, respectively, were not detected. In the juvenile, mutant testes exhibited a progressive loss of differentiating spermatogonia and a block in spermatid elongation, followed by extensive germ cell degeneration. Sertoli cell-specific Sin3a deletion also suppressed teratoma formation by fetal germ cells in an in vivo transplantation assay. We conclude that the epigenome of Sertoli cells influences the establishment of a niche for germline stem cells as well as for tumor initiating cells. PMID- 20572011 TI - Comparison of reprogramming efficiency between transduction of reprogramming factors, cell-cell fusion, and cytoplast fusion. AB - Reprogramming human somatic cells into pluripotent cells opens up new possibilities for transplantation therapy, the study of disease, and drug screening. In addition to somatic cell nuclear transfer, several approaches to reprogramming human cells have been reported: transduction of defined transcription factors to generate induced pluripotent stem cell (iPSC), human embryonic stem cell (hESC)-somatic cell fusion, and hESC cytoplast-somatic cell fusion or exposure to extracts of hESC. Here, we optimized techniques for hESC human fibroblast fusion and enucleation and cytoplast fusion, and then compared the reprogramming efficiency between iPSC generation, cell-fusion and cytoplast fusion. When compared with iPSC, hESC-fusion provided much faster and efficient reprogramming of somatic cells. The reprogramming required more than 4 weeks and the efficiency was less than 0.001% in iPSC generation, and it was less than 10 days and more than 0.005% in hESC-fusion. In addition, fusion yielded almost no partially reprogrammed cell colonies. However, the fused cells were tetraploid or aneuploid. hESC cytoplast fusion could initiate reprogramming but was never able to complete reprogramming. These data indicate that in cell fusion, as in nuclear transfer, reprogramming through direct introduction of a somatic nucleus into the environment of a pluripotent cell provides relatively efficient reprogramming. The findings also suggest that the nucleus of the host pluripotent cell may contain components that accelerate the reprogramming process. PMID- 20572010 TI - ATP-sensitive K(+) channel-deficient dilated cardiomyopathy proteome remodeled by embryonic stem cell therapy. AB - Transplantation of pluripotent stem cells has proven beneficial in heart failure, yet the proteomic landscape underlying repair remains largely uncharacterized. In a genetic model of dilated cardiomyopathy elicited by pressure overload in the KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) null mutant, proteome-wide profiles were here resolved by means of a systems approach prior to and following disease manifestation in the absence or presence of embryonic stem cell treatment. Comparative two-dimensional gel electrophoresis revealed a unique cardiomyopathic proteome in the absence of therapy, remodeled in response to stem cell treatment. Specifically, linear ion trap quadrupole Orbitrap mass spectrometry determined the identities of 93 and 109 differentially expressed proteins from treated and untreated cardiomyopathic hearts, respectively. Mapped protein-protein relationships and corresponding neighborhoods incorporated the stem cell-dependent subproteome into a nonstochastic network with divergent composition from the stem cell-independent counterpart. Stem cell intervention produced a distinct proteome signature across a spectrum of biological processes ranging from energetic metabolism, oxidoreductases, and stress-related chaperones to processes supporting protein synthesis/degradation, signaling, and transport regulation, cell structure and scaffolding. In the absence of treatment, bioinformatic interrogation of the disease-only proteome network prioritized adverse cardiac outcomes, ablated or ameliorated following stem cell transplantation. Functional and structural measurements validated improved myocardial contractile performance, reduced ventricular size and decreased cardiac damage in the treated cohort. Unbiased systems assessment unmasked "cardiovascular development" as a prioritized biological function in stem cell-reconstructed cardiomyopathic hearts. Thus, embryonic stem cell treatment transformed the cardiomyopathic proteome to demote disease-associated adverse effects and sustain a procardiogenic developmental response, supplying a regenerative substrate for heart failure repair. PMID- 20572012 TI - Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells. AB - The epithelial-to-mesenchymal transition (EMT) is an embryonic process that becomes latent in most normal adult tissues. Recently, we have shown that induction of EMT endows breast epithelial cells with stem cell traits. In this report, we have further characterized the EMT-derived cells and shown that these cells are similar to mesenchymal stem cells (MSCs) with the capacity to differentiate into multiple tissue lineages. For this purpose, we induced EMT by ectopic expression of Twist, Snail, or transforming growth factor-beta in immortalized human mammary epithelial cells. We found that the EMT-derived cells and MSCs share many properties including the antigenic profile typical of MSCs, that is, CD44(+), CD24(-), and CD45(-). Conversely, MSCs express EMT-associated genes, such as Twist, Snail, and mesenchyme forkhead 1 (FOXC2). Interestingly, CD140b (platelet-derived growth factor receptor-beta), a marker for naive MSCs, is exclusively expressed in EMT-derived cells and not in their epithelial counterparts. Moreover, functional analyses revealed that EMT-derived cells but not the control cells can differentiate into alizarin red S-positive mature osteoblasts, oil red O-positive adipocytes and alcian blue-positive chondrocytes similar to MSCs. We also observed that EMT-derived cells but not the control cells invade and migrate towards MDA-MB-231 breast cancer cells similar to MSCs. In vivo wound homing assays in nude mice revealed that the EMT-derived cells home to wound sites similar to MSCs. In conclusion, we have demonstrated that the EMT derived cells are similar to MSCs in gene expression, multilineage differentiation, and ability to migrate towards tumor cells and wound sites. PMID- 20572013 TI - NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35. AB - The emergence of drug-resistant malaria parasites is the major threat to effective malaria control, prompting a search for novel compounds with mechanisms of action that are different from the traditionally used drugs. The immunosuppressive drug FK506 shows an antimalarial activity. The mechanism of the drug action involves the molecular interaction with the parasite target proteins PfFKBP35 and PvFKBP35, which are novel FK506 binding protein family (FKBP) members from Plasmodium falciparum and Plasmodium vivax, respectively. Currently, molecular mechanisms of the FKBP family proteins in the parasites still remain elusive. To understand their functions, here we have determined the structures of the FK506 binding domain of Plasmodium vivax (PvFKBD) in unliganded form by NMR spectroscopy and in complex with FK506 by X-ray crystallography. We found out that PvFKBP35 exhibits a canonical FKBD fold and shares kinetic profiles similar to those of PfFKBP35, the homologous protein in P. falciparum, indicating that the parasite FKBP family members play similar biological roles in their life cycles. Despite the similarity, differences were observed in the ligand binding modes between PvFKBD and HsFKBP12, a human FKBP homolog, which could provide insightful information into designing selective antimalarial drug against the parasites. PMID- 20572015 TI - Aberrant epigenetic silencing of tumor suppressor genes is reversed by direct reprogramming. AB - Direct reprogramming procedures reset the epigenetic memory of cells and convert differentiated somatic cells into pluripotent stem cells. In addition to epigenetic memory of cell identity, which is established during development, somatic cells can accumulate abnormal epigenetic changes that can contribute to pathological conditions. Aberrant promoter hypermethylation and epigenetic silencing of tumor suppressor genes (TSGs) are now recognized as an important mechanism in tumor initiation and progression. Here, we have studied the fate of the silenced TSGs p16(CDKN2A) during direct reprogramming. We find that following reprogramming, p16 expression is restored and is stably maintained even when cells are induced to differentiate. Large-scale methylation profiling of donor cells identified aberrant methylation at hundreds of additional sites. Methylation at many, but not all these sites was reversed following reprogramming. Our results suggest that reprogramming approaches may be applied to repair the epigenetic lesions associated with cancer. PMID- 20572014 TI - The structure and evolution of the murine inhibitor of carbonic anhydrase: a member of the transferrin superfamily. AB - The original signature of the transferrin (TF) family of proteins was the ability to bind ferric iron with high affinity in the cleft of each of two homologous lobes. However, in recent years, new family members that do not bind iron have been discovered. One new member is the inhibitor of carbonic anhydrase (ICA), which as its name indicates, binds to and strongly inhibits certain isoforms of carbonic anhydrase. Recently, mouse ICA has been expressed as a recombinant protein in a mammalian cell system. Here, we describe the 2.4 A structure of mouse ICA from a pseudomerohedral twinned crystal. As predicted, the structure is bilobal, comprised of two alpha-beta domains per lobe typical of the other family members. As with all but insect TFs, the structure includes the unusual reverse gamma-turn in each lobe. The structure is consistent with the fact that introduction of two mutations in the N-lobe of murine ICA (mICA) (W124R and S188Y) allowed it to bind iron with high affinity. Unexpectedly, both lobes of the mICA were found in the closed conformation usually associated with presence of iron in the cleft, and making the structure most similar to diferric pig TF. Two new ICA family members (guinea pig and horse) were identified from genomic sequences and used in evolutionary comparisons. Additionally, a comparison of selection pressure (dN/dS) on functional residues reveals some interesting insights into the evolution of the TF family including that the N-lobe of lactoferrin may be in the process of eliminating its iron binding function. PMID- 20572016 TI - MUT-TP53 2.0: a novel versatile matrix for statistical analysis of TP53 mutations in human cancer. AB - Analysis of the literature reporting p53 mutations shows that 8% of report display typographical mistakes with a notable increase in recent years. These errors are sometimes isolated, but in some cases, they concern several or even all mutations described in a single article. Furthermore, some works report unusual profile of p53 mutations whose accuracy is difficult to assess. To handle these problems we have developed MUT-TP53 2.0, an accurate and powerful tool that will automatically handle p53 mutations and generate tables ready for publication that will lower the risk of typographical errors. Furthermore, using functional and statistical information issued from the UMD p53 database, it allows to assess the biological activity and the likelihood of every p53 mutant. PMID- 20572017 TI - Probing local structural fluctuations in myoglobin by size-dependent thiol disulfide exchange. AB - All proteins undergo local structural fluctuations (LSFs) or breathing motions. These motions are likely to be important for function but are poorly understood. LSFs were initially defined by amide hydrogen exchange (HX) experiments as opening events, which expose a small number of backbone amides to (1)H/(2)H exchange, but whose exchange rates are independent of denaturant concentration. Here, we use size-dependent thiol-disulfide exchange (SX) to characterize LSFs in single cysteine-containing variants of myoglobin (Mb). SX complements HX by providing information on motions that disrupt side chain packing interactions. Most importantly, probe reagents of different sizes and chemical properties can be used to characterize the size of structural opening events and the properties of the open state. We use thiosulfonate reagents (126-274 Da) to survey access to Cys residues, which are buried at specific helical packing interfaces in Mb. In each case, the free energy of opening increases linearly with the radius of gyration of the probe reagent. The slope and the intercept are interpreted to yield information on the size of the opening events that expose the buried thiol groups. The slope parameter varies by over 10-fold among Cys positions tested, suggesting that the sizes of breathing motions vary substantially throughout the protein. Our results provide insight to the longstanding question: how rigid or flexible are proteins in their native states? PMID- 20572018 TI - Developmental expression of human hemoglobins mediated by maturation of their subunit interfaces. AB - Different types of human hemoglobins (Hbs) consisting of various combinations of the embryonic, fetal, and adult Hb subunits are present at certain times during development representing a major paradigm of developmental biology that is still not understood and one which we address here. We show that the subunit interfaces of these Hbs have increasing bonding strengths as demonstrated by their distinct distribution of tetramers, dimers, and monomers during gel filtration at very low Hb concentration. This maturation is mediated by competition between subunits for more favorable partners with stronger subunit interactions. Thus, the protein products of gene expression can themselves have a role in the developmental process due to their intrinsic properties. PMID- 20572019 TI - The dimeric transmembrane domain of prolyl dipeptidase DPP-IV contributes to its quaternary structure and enzymatic activities. AB - Dipeptidyl peptidase IV (DPP-IV) is a drug target in the treatment of human type II diabetes. It is a type II membrane protein with a single transmembrane domain (TMD) anchoring the extracellular catalytic domain to the membrane. DPP-IV is active as a dimer, with two dimer interacting surfaces located extracellularly. In this study, we demonstrate that the TM of DPP-IV promotes DPP-IV dimerization and rescues monomeric DPP-IV mutants into partial dimers, which is specific and irreplaceable by TMs of other type II membrane proteins. By bioluminescence resonance energy transfer (BRET) and peptide electrophoresis, we found that the TM domain of DPP-IV is dimerized in mammalian cells and in vitro. The TM dimer interaction is very stable, based on our results with TM site-directed mutagenesis. None of the mutations, including the introduction of two prolines, resulted in their complete disruption to monomers. However, these TM proline mutations result in a significant reduction of DPP-IV enzymatic activity, comparable to what is found with mutations near the active site. A systematic analysis of TM structures deposited in the Protein Data Bank showed that prolines in the TM generally produce much bigger kinking angles than occur in nonproline containing TMs. Thus, the proline-dependent reduction in enzyme activity may result from propagated conformational changes from the TM to the extracellular active site. Our results demonstrate that TM dimerization and conformation contribute significantly to the structure and activity of DPP-IV. Optimal enzymatic activity of DPP-IV requires an optimal interaction of all three dimer interfaces, including its TM. PMID- 20572020 TI - Interaction of an ionic complementary peptide with a hydrophobic graphite surface. AB - Protein adsorption on a surface plays an important role in biomaterial science and medicine. It is strongly related to the interaction between the protein residues and the surface. Here we report all-atom molecular dynamics simulations of the adsorption of an ionic complementary peptide, EAK16-II, to the hydrophobic highly ordered pyrolytic graphite surface. We find that, the hydrophobic interaction is the main force to govern the adsorption, and the peptide interchain electrostatic interaction affects the adsorption rate. Under neutral pH condition, the interchain electrostatic attraction facilitates the adsorption, whereas under acidic and basic conditions, because of the protonation and deprotonation of glutamic acid and lysine residues, respectively, the resulting electrostatic repulsion slows down the adsorption. We also found that under basic condition, during the adsorption peptide Chain II will be up against a choice to adsorb to the surface through the hydrophobic interaction or to form a temporary hydrophobic core with the deposited peptide Chain I. These results provide a basis for understanding some of the fundamental interactions governing peptide adsorption on the surface, which can shed new light on novel applications, such as the design of implant devices and drug delivery materials. PMID- 20572021 TI - Topology of the disulfide bonds in the antiviral lectin scytovirin. AB - The antiviral lectin scytovirin (SVN) contains a total of five disulfide bonds in two structurally similar domains. Previous reports provided contradictory results on the disulfide pairing in each individual domain, and we have now re-examined the disulfide topology. N-terminal sequencing and mass spectrometry were used to analyze proteolytic fragments of native SVN obtained at acidic pH, yielding the assignment as Cys7-Cys55, Cys20-Cys32, Cys26-Cys38, Cys68-Cys80, and Cys74-Cys86. We also analyzed the N-terminal domain of SVN (SD1, residues 1-48) prepared by expression/oxidative folding of the recombinant protein and by chemical synthesis. The disulfide pairing in the chemically synthesized SD1 was forced into predetermined topologies: SD1A (Cys20-Cys26, Cys32-Cys38) or SD1B (Cys20 Cys32, Cys26-Cys38). The topology of native SVN was found to be in agreement with the SD1B and the one determined for the recombinant SD1 domain. Although the two synthetic forms of SD1 were distinct when subjected to chromatography, their antiviral properties were indistinguishable, having low nM activity against HIV. Tryptic fragments, the "cystine clusters" [Cys20-Cys32/Cys26-Cys38; SD1] and [Cys68-Cys80/Cys74-C-86; SD2], were found to undergo rapid disulfide interchange at pH 8. This interchange resulted in accumulation of artifactual fragments in alkaline pH digests that are structurally unrelated to the original topology, providing a rational explanation for the differences between the topology reported herein and the one reported earlier (Bokesh et al., Biochemistry 2003;42:2578-2584). Our observations emphasize the fact that proteins such as SVN, with disulfide bonds in close proximity, require considerable precautions when being fragmented for the purpose of disulfide assignment. PMID- 20572022 TI - Fish consumption, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study. AB - Marine n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for bone health, but few studies have investigated the association with fish consumption. Our aim was to study associations of fish and EPA + DHA consumption with bone mineral density (BMD) and hip fracture risk and determine whether high linoleic acid (LA) intake, the major dietary n-6 PUFA, modifies the associations. The study population consisted of 5045 participants aged 65 years and older from the Cardiovascular Health Study. Data on BMD were available for 1305 participants. Food-frequency questionnaire was used to assess dietary intake, and hip fracture incidence was assessed prospectively by review of hospitalization records. After multivariable adjustment, femoral neck BMD was 0.01 g/cm(2) lower in the highest versus lowest tuna/other-fish intake category (p = .05 for trend). EPA + DHA intake (higher versus lower median of 0.32 g/day) was associated with lower femoral neck BMD (0.66 versus 0.71 g/cm(2), p < .001) among those with LA intake greater than the median 12.1 g/day (p = .03 for interaction). No significant associations were found with total-hip BMD. During mean follow-up of 11.1 years, 505 hip fractures occurred. Fish or EPA + DHA consumption was not significantly associated with fracture incidence [hazard ratio (HR) for extreme categories: HR = 1.23, 95% confidence interval (CI) 0.83-1.84 for tuna/other fish; HR = 1.16, 95% CI 0.91 1.49 for fried fish; and HR = 0.98, 95% CI 0.71-1.36 for EPA + DHA]. High LA intake did not modify these associations. In this large prospective cohort of older adults, fish consumption was associated with very small differences in BMD and had no association with hip fracture risk. PMID- 20572024 TI - Fluoxetine and infantile hypertrophic pylorus stenosis: a signal from a birth defects-drug exposure surveillance study. AB - PURPOSE: We report an association found in a surveillance study which systematically evaluated combinations of specific birth defects and drugs used in the first trimester of pregnancy. METHOD: The database of a population-based birth defects registry (birth years 1997-2007) was systematically screened for combinations of drugs and malformations that were disproportionately present compared to the rest of the database. Combinations with at least three exposed cases and a p < 0.01 (Fisher Exact test) were studied to analyse details of the malformation, timing of exposure, and additional case-control analyses. RESULTS: Among the significant associations found, an association between maternal use of fluoxetine and infantile hypertrophic pyloric stenosis (IHPS) was of particular interest. In total 3/178 (1.7%) of the children with a HPS were exposed to fluoxetine in the first trimester compared to 8/4077 (0.2%) fluoxetine exposures among the children with other malformations (p = 0.009, OR = 8.7, 95%CI = 2.3 33.2). The three exposed cases were all isolated and fluoxetine was used in gestational weeks 4-8, 2-8 and -10-19, respectively. In additional case-control analyses, using controls with a genetic disorder and after adjustment for maternal age and smoking in the first trimester of pregnancy, the adjusted odds ratio was 9.8 (95% confidence interval: 1.5-62.0). CONCLUSIONS: Because we cannot rule out the possibility that the association between IHPS and fluoxetine is caused by chance, we encourage other investigators to study the association between IHPS and fluoxetine in their data. PMID- 20572025 TI - Sample size for post-marketing safety studies based on historical controls. AB - PURPOSE: As part of a drug's entire life cycle, post-marketing studies are an important part in the identification of rare, serious adverse events. Recently, the US Food and Drug Administration (FDA) has begun to implement new post marketing safety mandates as a consequence of increased emphasis on safety. The purpose of this research is to provide exact sample size formula for the proposed hybrid design, based on a two-group cohort study with incorporation of historical external data. METHODS: Exact sample size formula based on the Poisson distribution is developed, because the detection of rare events is our outcome of interest. Performance of exact method is compared to its approximate large-sample theory counterpart. RESULTS: The proposed hybrid design requires a smaller sample size compared to the standard, two-group prospective study design. In addition, the exact method reduces the number of subjects required in the treatment group by up to 30% compared to the approximate method for the study scenarios examined. CONCLUSIONS: The proposed hybrid design satisfies the advantages and rationale of the two-group design with smaller sample sizes generally required. PMID- 20572023 TI - Correlates of trabecular and cortical volumetric bone mineral density at the femoral neck and lumbar spine: the osteoporotic fractures in men study (MrOS). AB - The objective of this cross-sectional analysis was to examine the correlates of trabecular and cortical volumetric bone mineral density (vBMD) in 3670 community dwelling men, mean age 73.6 +/- 5.9 years. vBMD was measured by quantitative computed tomography (QCT) and areal BMD by dual-energy X-ray absorptiometry (DXA). Demographic, historical, and lifestyle information was obtained by interview, and height, weight, and neuromuscular function were determined by examination. To express the strength of the associations, percent differences (95% confidence interval) were calculated from multivariable linear regression models using the formula 100 (beta * unit/mean BMD). Units for continuous variables were chosen to approximate 1 standard deviation (SD). The multivariable linear regression models predicted 15%, 21%, and 20% of the overall variance in trabecular and cortical vBMD of the femoral neck and vBMD of the lumbar spine, respectively. Diabetes was associated with a 16.5% greater trabecular vBMD at the femoral neck and 11% at the lumbar spine but less than 2% for cortical vBMD. For femoral neck trabecular vBMD, the strongest negative correlates were past smoking (-9%), fracture history (-15%), kidney stones (-7%), corticosteroids (-11%), and insulin therapy (-26%). For cortical vBMD, the strongest negative correlate was use of thyroid medication (-2.8%). The strongest negative correlates for lumbar spine trabecular vBMD were fracture history (-5%), antiandrogen use (-19%), height (-8%), and thiazoliainedione use (-22%). Bioavailable estradiol and testosterone levels were positively related and sex hormone-binding globulin was negatively related to trabecular vBMD of the spine. There was no relationship between sex hormones and femoral neck trabecular vBMD. Our conclusion is that correlates of trabecular vBMD and cortical vBMD appear to differ in older men. PMID- 20572026 TI - Ghrelin improves disturbed myocardial energy metabolism in rats with heart failure induced by isoproterenol. AB - To explore the effects of ghrelin on disturbed myocardial energy metabolism during chronic heart failure (CHF). Rats were subcutaneously injected with isoproterenol (ISO) for 10 days with or without ghrelin for another 10 days. Enzyme immunoassay was to measure ghrelin concentrations. Compared with the control group, ISO-treated rats showed suppressed cardiac function with high ghrelin/GHS-R expressions. These rats also showed the decreases in food consumption and weight. The decreased levels of plasma glucose and myocardial glucogen, but the high lactate in blood and myocardium showed myocardial metabolic disturbance. Compared with the group given ISO alone, the rats with ghrelin (20 and 100 microg/kg/day) improved cardiac dysfunction and increased food intake by 13.5 and 14.2% (both P < 0.01), and rate of weight gain by 95% (P < 0.05) and 1.71-fold (P < 0.01), respectively. The plasma glucose were increased by 49.7 and 50.8% (both P < 0.01), and myocardial glucogen, by 40.5 and 51.7% (both P < 0.01), but blood lactate decreased by 1.56- and 1.96-fold (both P < 0.01), and myocardial lactate by 32.1 and 48.7% (both P < 0.05), respectively. Their MCT1 mRNA and protein expressions increased. The myocardial ghrelin/GHS-R pathway can be upregulated during CHF. The ghrelin can attenuate cardiac dysfunction and energy metabolic disturbance in CHF rats. PMID- 20572028 TI - Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer. AB - BACKGROUND: Both concomitant chemotherapy and altered fractionation radiotherapy (RT) have been shown to improve outcomes for patients with locoregionally advanced head and neck squamous cell carcinomas. However, both strategies also increase acute toxicity, and it is questionable whether the 2 can be safely combined. Traditional concomitant chemotherapy regimens include high-dose cisplatin given at 100 mg/m2 every 3 weeks. The authors' purpose was to report efficacy and toxicity after weekly cisplatin (30 mg/m2/wk) concurrent with altered fractionation RT. METHODS: One hundred twenty-one patients with American Joint Committee on Cancer stages II (3%), III (13%), or IV (84%) squamous cell carcinomas of the oropharynx (70%), hypopharynx (20%), or larynx (10%) were treated between 2000 and 2006 at the University of Florida with hyperfractionated RT (55 patients) or concomitant boost RT (66 patients) and concomitant cisplatin (30 mg/m2/wk). RESULTS: Median follow-up was 2.9 years; median follow-up on survivors was 3.6 years. Seventy-nine percent of patients completed >=6 cycles of chemotherapy; 94% received >=7200 centigrays. Seven (6%) patients changed from cisplatin to carboplatin because of bone marrow toxicity. Gastrostomy tube feeding was required in 54% of patients either before (16%) or during RT (38%). Two (1.6%) patients died from therapy-related complications. The 5-year outcomes were: local control, 83%; locoregional control, 79%; distant metastasis-free survival, 88%; cause-specific survival, 76%; and overall survival, 59%. Seven (6%) patients had severe late complications. Three (3%) patients required a permanent gastrostomy tube. CONCLUSIONS: Concomitant weekly cisplatin with altered fractionation RT is a safe and effective treatment regimen. PMID- 20572027 TI - Characterization of conantokin Rl-A: molecular phylogeny as structure/function study. AB - A multidisciplinary strategy for discovery of new Conus venom peptides combines molecular genetics and phylogenetics with peptide chemistry and neuropharmacology. Here we describe application of this approach to the conantokin family of conopeptides targeting NMDA receptors. A new conantokin from Conus rolani, ConRl-A, was identified using molecular phylogeny and subsequently synthesized and functionally characterized. ConRl-A is a 24-residue peptide containing three gamma-carboxyglutamic acid residues with a number of unique sequence features compared to conantokins previously characterized. The HPLC elution of ConRl-A suggested that this peptide exists as two distinct, slowly exchanging conformers. ConRl-A is predominantly helical (estimated helicity of 50%), both in the presence and absence of Ca(++). The order of potency for blocking the four NMDA receptor subtypes by ConRl-A was NR2B > NR2D > NR2A > NR2C. This peptide has a greater discrimination between NR2B and NR2C than any other ligand reported so far. In summary, ConRl-A is a new member of the conantokin family that expands our understanding of structure/function of this group of peptidic ligands targeted to NMDA receptors. Thus, incorporating phylogeny in the discovery of novel ligands for the given family of ion channels or receptors is an efficient means of exploring the megadiverse group of peptides from the genus Conus. PMID- 20572029 TI - Oxaliplatin-based chemotherapy (dexamethasone, high-dose cytarabine, and oxaliplatin)+/-rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma. AB - BACKGROUND: Patients affected by relapsed or primary refractory lymphomas currently have a poor prognosis and no standard salvage treatment options. This study was carried out to assess the efficacy and safety of a dexamethasone, high dose cytarabine, and oxaliplatin as salvage therapy in those patients, replacing cisplatin with oxaliplatin in the standard dexamethasone, cytarabine, and cisplatin scheme. METHODS: Seventy patients with relapsed or refractory aggressive non-Hodgkin or Hodgkin lymphoma were treated from September 2001 to September 2007. The median age of patients was 51 years (range, 19-75 years). Histological subtypes were: diffuse large B-cell lymphoma (n=47) and Hodgkin lymphoma (n=23). The overall response rate was 73% (51 of 70), with 30 (43%) complete remissions and 21 (30%) partial remissions. Fifty-two patients were treated with dexamethasone, high-dose cytarabine, and oxaliplatin as second-line chemotherapy. Forty-eight patients were enrolled in an autologous stem cell transplantation program; forty (83%) finally proceeded to high-dose consolidation and autografting. RESULTS: No grade 3 or 4 nonhematological toxicity was demonstrated; in particular, no renal or neurotoxicity was reported. After a median follow-up period of 21 months (range, 2-87 months), 22 (31%) patients had died. Probabilities of 2-year progression-free survival (PFS) and overall survival (OS) were 44% and 71%, respectively. In the chemosensitive patients, the PFS and OS were 52% and 83%, respectively. The only factor that significantly correlated with better OS was the response to therapy. CONCLUSIONS: This study confirms that dexamethasone, high-dose cytarabine, and oxaliplatin +/- rituximab is an effective and feasible outpatient regimen for salvage therapy in patients affected by relapsed or refractory lymphoma. Moreover, the feasibility and efficacy of this scheme as an in vivo chemosensitive test in patients in autotransplantation programs was confirmed. PMID- 20572030 TI - Influence of patients' preferences and treatment site on cancer patients' end-of life care. AB - BACKGROUND: Research suggests that patients' end-of-life (EOL) care is determined primarily by the medical resources available, and not by patient preferences. The authors examined whether patients' desire for life-extending therapy was associated with their EOL care. METHODS: Coping with Cancer is a multisite, prospective, longitudinal study of patients with advanced cancer. Three hundred one patients were interviewed at baseline and followed until death, a median of 4.5 months later. Multivariate analyses examined the influence of patients' preferences and treatment site on whether patients received intensive care or hospice services in the final week of life. RESULTS: Eighty-three of 301 patients (27.6%) with advanced cancer wanted life-extending therapy at baseline. Patients who understood that their disease was terminal or who reported having EOL discussions with their physicians were less likely to want life-extending care compared with others (23.4% vs 42.6% and 20.7% vs 44.4%, respectively; P<=.003). Patients who were treated at Yale Cancer Center received more intensive care (odds ratio [OR], 3.14; 95% confidence interval [CI], 1.16-8.47) and less hospice services (OR, 0.52; 95% CI, 0.29-0.92) compared with patients who were treated at Parkland Hospital. However, in multivariate analyses that controlled for confounding influences, patients who preferred life-extending care were more likely to receive intensive care (adjusted OR [AOR], 2.91; 95% CI, 1.09-7.72) and were less likely to receive hospice services (AOR, 0.45; 95% CI, 0.26-0.78). Treatment site was not identified as a significant predictor of EOL care. CONCLUSIONS: The treatment preferences of patients with advanced cancer may play a more important role in determining the intensity of medical care received at the EOL than previously recognized. Future research is needed to determine the mechanisms by which patients' preferences for care and treatment site interact to influence EOL care. PMID- 20572031 TI - The antitumor activity of NK012, an SN-38-incorporating micelle, in combination with bevacizumab against lung cancer xenografts. AB - BACKGROUND: It has been demonstrated that NK012, a novel 7-ethyl-10 hydroxycamptothecin (SN-38)-incorporating polymeric micelle, exerts significantly more potent antitumor activity against various human tumor xenografts than irinotecan (CPT-11) (a water-soluble prodrug of SN-38). Combination therapy of anticancer agents with bevacizumab (Bv), an anti-vascualr endothelial growth factor humanized monoclonal antibody, has more potently inhibited tumor growth than either agent alone. In the current study, the authors examined the antitumor effect of NK012 in combination with Bv against human lung cancer. METHODS: Nude mice bearing lung adenocarcinoma (PC-14 or A549 xenografts) were administered NK012 at SN-38-equivalent doses of 5 mg/kg or 30 mg/kg in combination with or without Bv at 5 mg/kg. CPT-11 at a dose of 66.7 mg/kg was administered with or without Bv at a dose of 5 mg/kg in the same experimental model. To evaluate interaction with Bv, the pharmacokinetics and microvessel density in tumors that were treated on each regimen were analyzed. RESULT: In vitro, the growth inhibitory effect of NK012 was 50-fold more potent than that of CPT-11 and was almost equivalent to that of SN-38. In vivo studies revealed that the combination of NK012 plus Bv had significantly greater antitumor activity against human lung cancer xenografts compared with NK012 alone (PC-14, P=.0261; A549, P<.001). The pharmacokinetic profile of NK012 revealed that coadministration of Bv did not interfere with the accumulation of NK012. CONCLUSIONS: In this study, significant antitumor activity was noted with NK012 in combination with Bv against lung cancer cells. The current results warrant the clinical evaluation of NK012 in lung cancer. PMID- 20572032 TI - Translating research into evidence-based practice: the National Cancer Institute Community Clinical Oncology Program. AB - The recent rapid acceleration of basic science is reshaping both our clinical research system and our healthcare delivery system. The pace and growing volume of medical discoveries are yielding exciting new opportunities, yet we continue to face old challenges to maintain research progress and effectively translate research into practice. The National Institutes of Health and individual government programs increasingly are emphasizing research agendas that involve evidence development, comparative-effectiveness research among heterogeneous populations, translational research, and accelerating the translation of research into evidence-based practice as well as building successful research networks to support these efforts. For more than 25 years, the National Cancer Institute Community Clinical Oncology Program has successfully extended research into the community and facilitated the translation of research into evidence-based practice. By describing its keys to success, this article provides practical guidance to cancer-focused, provider-based research networks as well as those in other disciplines. PMID- 20572033 TI - Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. AB - BACKGROUND: Antiangiogenic therapy has become the most important treatment modality for patients with advanced hepatocellular carcinoma (HCC). In this study, the authors investigated levels of alpha-fetoprotein (AFP) as a potential biomarker for treatment efficacy of antiangiogenic therapy. METHODS: Patients with advanced HCC who had been enrolled in 3 prospective phase 2 clinical trials that evaluated either sorafenib, bevacizumab, or thalidomide in combination with a potentially antiangiogenic, metronomic, oral 5-fluoropyrimidine as first-line systemic therapy were included. An early AFP response was defined as a decline >20% from baseline after 2 to 4 weeks of treatment. AFP response was analyzed for its association with treatment efficacy and survival outcome. RESULTS: Seventy two patients were included for early AFP response evaluation, and 12 of those patients (17%) were classified as early AFP responders. Early AFP responders, compared with nonresponders, had a significantly improved overall response rate (33% vs 8%; P=.037) and a significantly improved disease control rate (83% vs 35%; P=.002), which was defined as the percentage of patients who had an objective response plus stable disease for a minimum of 8 weeks. AFP responders, compared with nonresponders, also had longer median progression-free survival (PFS) (7.5 months vs 1.9 months; P=.001) and longer median overall survival (OS) (15.3 months vs 4.1 months; P=.019). In a multivariate analysis, AFP response remained a significant independent predictor of better PFS and OS. CONCLUSIONS: The current results indicated that an early AFP response is a useful surrogate marker to predict treatment response and prognosis in patients with advanced HCC who receive antiangiogenic therapy. PMID- 20572034 TI - Predictors of anticoagulation in hospice patients with lung cancer. AB - BACKGROUND: Guidelines recommend lifelong anticoagulation in patients with cancer and a history of thromboembolism, but the use of anticoagulation in hospice has not been described. A retrospective study of medication data was conducted to determine patterns of anticoagulant use and predictors of type of anticoagulant prescribed for hospice patients with lung cancer. METHODS: Medication data were evaluated for 16,896 hospice patients with lung cancer in 2006 to determine patient and hospice characteristics that predicted anticoagulant prescription. Independent predictors of warfarin versus low molecular weight heparin (LMWH) prescription were identified using a logistic regression model. RESULTS: One of every 11 patients was prescribed an anticoagulant, most commonly warfarin. Compared with patients prescribed LMWH, patients prescribed warfarin were older (71.6 vs 65.8 years, P<.001), were more likely white (81.2% vs 74.3%, P = .03), had a longer stay in hospice (median 21 days vs 17 days, P = .001), and were more likely to have >=3 comorbid illnesses (37.5% vs 25.0%, P<.001). The strongest independent predictor of type of anticoagulant prescribed was geographic region, with hospices in the Northeast more likely to prescribe LMWH. CONCLUSIONS: Anticoagulant use is prevalent in patients with lung cancer enrolled in hospice. This study highlights the need to understand the benefits and risks of anticoagulation at the end of life. PMID- 20572035 TI - Expression of p16 in lymph node metastases of adjuvantly treated stage III colorectal cancer patients identifies poor prognostic subgroups: a retrospective analysis of biomarkers in matched primary tumor and lymph node metastases. AB - BACKGROUND: The objective of identifying protein biomarkers for patients with stage III and IV colorectal cancer is to improve risk stratification and, thus, to identify patients in the postoperative setting who may benefit from more targeted treatment. The objective of the current study was to determine the prognostic value of 19 protein markers assessed in primary tumors and matched lymph node (LN) metastases from patients with stage III and IV colorectal cancer. METHODS: Matched primary tumors and LN metastases from 82 patients with stage III and IV colorectal cancer were mounted onto a multiple-punch tissue microarray and were stained for 19 protein markers involved in tumor progression (beta-catenin, E-cadherin, epidermal growth factor receptor, phosphorylated extracellular signal regulated kinase [pERK], receptor for hyaluronic acid-mediated motility, phosphorylated protein kinase B, p21, p16, B-cell lymphoma 2, Ki67, apoptotic protease activating factor 1, mammalian sterile 20-like kinase 1, Raf kinase inhibitor protein, vascular endothelial growth factor, ephrin type-B receptor 2, matrix metalloproteinase 7, laminin5gamma2, mucin 1 [MUC1], and caudal-related homeobox 2). The prognostic effects of biomarkers in both primary tumor and positive LNs were assessed. RESULTS: MUC1, pERK and p16 in LN (P=.002, P=.014, and P=.002, respectively) had independent prognostic value. In patients with stage III disease who received adjuvant treatment, negative p16 expression was associated with highly unfavorable outcomes overall (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.1-0.6; P=.005) when the analysis was stratified by pathologic tumor classification (HR, 0.25; 95% CI, 0.1-0.7; P=.005), age (HR, 0.23; 95% CI, 0.1-0.6; P=.004), and LN ratio (HR, 0.26; 95% CI, 0.1-0.7; P=.007); and, in multivariate analysis, it was associated with performance status and the receipt of folic acid treatment (HR, 0.29; 95% CI, 0.09-0.89; P=.03). CONCLUSIONS: The loss of p16 in LN metastases contributed to adverse outcomes in adjuvantly treated patients with stage III colorectal cancer independent of pathologic tumor classification, age, LN ratio, performance status, or folic acid treatment. The current results support the investigation of p16 as a prognostic and potential predictive biomarker for future randomized trials of patients with stage III colorectal cancer. PMID- 20572036 TI - Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer. AB - BACKGROUND: Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity-modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana-Farber Cancer Institute (DFCI) with IMRT-based chemoradiotherapy with or without surgery for locally recurrent SCCHN. METHODS: The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT. The primary endpoint was overall survival (OS), and secondary endpoints were locoregional (LRC) and distant control and acute and chronic toxicity. RESULTS: Thirty-five patients were treated from August 2004 until December 2008. Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients). The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy. The median follow-up was 2.3 years. The 2-year actuarial OS and LRC rates were 48% and 67%, respectively. Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity. Four (11%) late deaths occurred in patients with no evidence of disease (2 aspiration events, 1 oropharyngeal hemorrhage, and 1 infectious death). CONCLUSIONS: Aggressive chemoradiotherapy with IMRT was found to be feasible and resulted in favorable survival outcomes in comparison with published reports. Acute and late toxicities were substantial. The apparently improved LRC appears to carry a significant risk of developing late complications. PMID- 20572037 TI - Anthracycline dose intensification in adult acute lymphoblastic leukemia: lack of benefit in the context of the fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen. AB - BACKGROUND: In previous studies of frontline therapy for adult acute lymphoblastic leukemia (ALL), early treatment with higher doses of anthracyclines has been reported to improve outcome. The current study was conducted to evaluate whether addition of anthracycline-based consolidation chemotherapy (Course 2) with liposomal daunorubicin (150 mg/m2 intravenously [IV] on Days 1 and 2) and cytarabine (1.5 g/m2 IV on Days 1 and 2) to the standard hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine) would improve outcome. METHODS: Sixty-eight consecutive adults with de novo ALL or lymphoblastic lymphoma were treated with this modified hyper-CVAD regimen inclusive of rituximab for CD20 expression>=20%. RESULTS: Sixty-three (93%) patients achieved complete response (CR). With a median follow-up of 90 months, the 5-year CR duration (CRD) and overall survival (OS) rates were 46% and 44%, respectively. Compared with 208 patients treated with standard hyper-CVAD (rates of 45% and 47%, respectively; P=not significant), outcome with the modified hyper-CVAD regimen was not improved overall. Outcome was improved by the addition of rituximab for the CD20-positive subset (rates of CRD and OS of 50% and 53%, respectively), whereas anthracycline intensification worsened outcome for the CD20-negative subset (rates of CRD and OS of 41% and 35%, respectively; P=.01) compared with standard hyper-CVAD. A high mortality rate related to infections in CR was noted among patients aged 60 years or older. CONCLUSIONS: In the context of the hyper-CVAD regimen, early anthracycline intensification did not improve outcome for adults with de novo ALL or lymphoblastic lymphoma. PMID- 20572038 TI - Attention and working memory abilities in children treated for acute lymphoblastic leukemia. AB - BACKGROUND: To extend investigation beyond global cognitive measures prevalent in the literature, this study examined attention and working memory (WM) abilities of survivors of childhood acute lymphoblastic leukemia (ALL), the separate contributions of attention and WM to intelligence quotient (IQ), and their association with neuroimaging changes. METHODS: Ninety-seven children with ALL received risk-directed therapy based on presenting clinical and biological factors. During consolidation therapy, low-risk patients received half the dose of intravenous methotrexate that standard-risk/high-risk patients received, and fewer doses of triple intrathecal therapy. Patients were classified according to end of consolidation magnetic resonance imaging scans (normal or leukoencephalopathy), and continuous measures of white matter structure were computed. As part of the protocol study, children completed cognitive assessment 2 years later (completion of therapy), using Digit Span Forward (DSF) for attention and Digit Span Backward (DSB) for WM. RESULTS: For the total sample and the standard-/high-risk group, Total Digit Span (TDS), DSF, and DSB were impaired relative to norms (P<.05). In the low-risk group, only DSB was impaired (P<.0001). Across groups, a higher percentage of patients performed below the average range (scale score<7) on DSB (66%) compared with the DSF (14%) or TDS (18%). Regression analysis indicated that DSB predicted estimated IQ (P<.05), after accounting for DSF. Leukoencephalopathy was predictive of lower TDS (P<.05). CONCLUSIONS: WM appears to be especially sensitive to treatment-related changes in ALL survivors, detecting difficulties potentially missed by global intelligence measures. These findings may facilitate the identification of vulnerable neural pathways and the development of targeted cognitive interventions. PMID- 20572039 TI - Relation between normal rectal methylation, smoking status, and the presence or absence of colorectal adenomas. AB - BACKGROUND: Colorectal cancer (CRC) is 1 of the leading causes of death in the Western world. CRC develops from premalignant lesions, chiefly colorectal adenomas. Currently, the most accurate and recommended screening method for finding colorectal adenomas is colonoscopy performed on all individuals aged>50 years. However, the costs and risks associated with this procedure are relatively high. The objectives of the current study were to correlate epigenetic alterations that occur in normal rectal mucosa, smoking status, and age with the presence or absence of concomitant colorectal adenomas and to assess the potential clinical value of methylation in normal rectal biopsies as a screening assay for the presence of polyps and, hence, the need for a full colonoscopy. METHODS: One hundred thirteen normal rectal mucosal biopsies from 113 patients were studied. DNA was extracted, modified with sodium bisulfite, and subjected to real-time quantitative, methylation-specific polymerase chain reaction analysis for the following genes: adenomatous polyposis coli (APC); cadherin 1, type 1, E cadherin (epithelial) (CDH1); estrogen receptor 1 (ESR1); cytokine high in normal 1 (HIN1); hyperplastic polyposis protein 1 (HPP1); O-6 methylguanine-DNA methyltransferase (MGMT); neural epidermal growth factor-like 1 (NELL1); splicing factor 3B, 14-kDa subunit (p14); cyclin-dependent kinase (CDK) inhibitor 2B (inhibits CDK4) (p15); retinoic acid receptor beta (RARbeta); somatostatin (SST); tachykinin, precursor 1 (TAC1); and tissue inhibitor of metalloproteinase (TIMP) metallopeptidase inhibitor 3 (TIMP3). Data were then analyzed using several proprietary software programs. RESULTS: By using several sets of genes, clinical characteristics, and multivariate analyses, the authors developed a prediction model for the presence of concomitant colorectal adenomas at the time of rectal biopsy. They also observed strong correlations between smoking status and rectal methylation pattern and between smoking status and the presence or risk of concomitant adenomas. CONCLUSIONS: A prediction model was developed for the presence of colorectal adenomas based on gene methylation patterns in the normal rectum. The results indicated that these genes may be involved in early stages of adenoma formation. The observed epigenetic alterations in these markers may be caused in part by the effects of smoking and/or age. Normal rectal methylation may be useful as a biomarker for narrowing the population in need of screening colonoscopy. PMID- 20572040 TI - Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. AB - BACKGROUND: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (>=5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. METHODS: Patients with high-grade soft tissue sarcoma>=8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). RESULTS: Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of disease-free survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. CONCLUSIONS: Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors. PMID- 20572041 TI - Activity and tolerability of nilotinib: a retrospective multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or intolerant. AB - BACKGROUND: Nilotinib is active in imatinib-resistant and -intolerant chronic myeloid leukemia patients and was recently approved for these indications. METHODS: Data on the efficacy and safety of nilotinib treatment were collected from 2 phase 2 expanded access clinical trials with similar designs (CAMN107AIL01 and ENACT). RESULTS: Of 88 study patients (58 chronic, 11 accelerated, 19 blast crisis), the best responses to nilotinib were complete hematologic response (CHR) in 27%, partial cytogenetic response in 12%, complete cytogenetic response in 14%, and major molecular response in 19%. Patients achieving at least a CHR during imatinib therapy were more likely to respond to nilotinib, and failure to achieve at least a CHR on imatinib therapy was predictive of progression or lack of response to nilotinib (P=.0021). Responses were not statistically different in subgroup analysis, including that of imatinib intolerance compared with imatinib resistance, presence of ABL kinase domain mutations compared with absence of mutations, and previous treatment with another second-generation tyrosine kinase inhibitor compared no prior treatment. The overall survival and progression-free survival rates at 1 year were 83% and 48% for the entire cohort, 93% and 66% in chronic phase, and 64% and 19% in advanced phase. Adverse hematological events included thrombocytopenia (all events, 27%; grade 3-4, 13%) and leukopenia (all events, 18%; grade 3-4, 10%). The majority of the nonhematological events were mild, the most common being rash, infection, bone pain, headache, nausea, and vomiting. CONCLUSIONS: Nilotinib treatment is an efficient and safe therapy for imatinib-resistant or -intolerant patients. Prior response to imatinib therapy is a predictor for the response to nilotinib. PMID- 20572042 TI - Invasive neuroendocrine carcinoma of the breast: a distinctive subtype of aggressive mammary carcinoma. AB - BACKGROUND: Neuroendocrine carcinoma (NEC) of the breast, a pathologic entity newly defined in the 2003 World Health Organization classification of tumors, is a rare type of tumor that is not well recognized or studied. The purpose of this first case-controlled study is to reveal the clinicopathologic features, therapeutic response, and outcomes of patients with NEC of the breast. METHODS: Seventy-four patients with NEC of the breast who were treated at The University of Texas M. D. Anderson Cancer Center were analyzed; 68 of them had complete clinical follow-up. Two cohorts of invasive mammary carcinoma cases were selected to pair with NEC to reveal demographic, pathologic, and clinical features at presentation, along with therapeutic response to treatment and patient outcomes. RESULTS: NEC was more likely to be estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative. Despite similar age and disease stages at presentation, NEC showed a more aggressive course than invasive ductal carcinoma, with a higher propensity for local and distant recurrence and poorer overall survival. High nuclear grade, large tumor size, and regional lymph node metastasis were significant negative prognostic factors for distant recurrence-free survival; high nuclear grade and regional lymph node metastasis were also significant negative prognostic factors for overall survival. Although endocrine therapy and radiation therapy showed a trend toward improved survival, the small number of cases in this study limited the statistical power to reveal therapeutic benefits in NEC of the breast. CONCLUSIONS: NEC is a distinct type of aggressive mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely different clinical entity. PMID- 20572043 TI - Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome: correlation to cytomorphology, cytogenetics, and clinical data. AB - BACKGROUND: The diagnosis and classification of myelodysplastic syndromes (MDS) is based on cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) may add important diagnostic information. METHODS: To evaluate the potential role of MFC in the diagnostic setting of MDS, the authors analyzed the results from 1013 patients with suspected MDS by using CM, CG, and MFC in parallel. RESULTS: Concordance between CM and MFC was 82% for diagnostic results in 788 patients who had unequivocal CM results. An additional 225 patients had only minor dysplastic features identified by CM, including 51 patients (22.7%) who had clear evidence of MDS by MFC. Twelve patients who had no indication of MDS identified by CM had MDS-typical CG aberrations; in 6 of those patients (50%), MFC revealed MDS characteristics. In another 11 of 23 patients (47.8%) who had minor dysplastic features identified by CM and MDS-typical CG aberrations, MFC revealed MDS characteristics. The percentages of blasts determined by CM and by MFC were strongly correlated (P<.001). The frequency of aberrantly expressed antigens differed significantly between patients rated by CM as MDS (highest frequencies), suspected MDS, and no MDS (lowest frequencies). In various patients, MFC identified MDS-typical aberrant antigen expression in cell compartments that were not rated dysplastic by CM. The numbers of aberrantly expressed antigens were correlated with International Prognostic Scoring System scores and overall survival. CONCLUSIONS: The current analysis clearly demonstrated an increased diagnostic yield with MFC when added to CM and CG in patients with suspected MDS. PMID- 20572044 TI - Understanding social obstacles to early breast cancer detection is critical to improving breast cancer outcome in low- and middle-resource countries. PMID- 20572045 TI - Characteristics and outcomes of elderly patients with primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center experience. AB - BACKGROUND: Approximately 50% of all patients with primary central nervous system lymphoma (PCNSL) are aged >=65 years; however, this group is relatively understudied, and to the authors's knowledge, optimal treatment for older patients is not well defined. METHODS: This was a retrospective review of PCNSL patients aged >=65 years who were treated at Memorial Sloan-Kettering Cancer Center between 1986 and 2008. A multivariate analysis of demographic and clinical variables on prognosis and receipt of treatment was performed. RESULTS: One hundred seventy-four patients between the ages of 65 and 89 years were identified; there was a slight predominance of women (52.9%). One hundred forty eight patients were treated with chemotherapy at the time of diagnosis (98% with methotrexate-based therapy) and 31 of these patients also received whole-brain radiotherapy (WBRT). Sixteen patients received WBRT alone. A radiographic response to chemotherapy was noted in 76% of patients. Ninety patients developed disease progression after initial treatment; 74 received salvage therapy and 48% of these patients responded to salvage treatment. The median overall survival was 25 months (range, 18-33 months), and the 3-year survival rate was 36%. Approximately 20.1% of patients were alive for >=11 years. WBRT was delivered more frequently before 1998, and patients with a history of prior malignancy were less likely to receive WBRT. Age and performance status were identified as the most important predictors of survival. Treatment-related neurotoxicity at 2 years was strongly associated with receipt of WBRT (P=.0002). CONCLUSIONS: PCNSL in the elderly remains sensitive to methotrexate-based chemotherapy and aggressive treatment may be warranted both at the time of diagnosis and disease recurrence. PMID- 20572046 TI - Interim report of a phase 2 clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma. AB - BACKGROUND: Novel therapies are needed to improve outcomes in T-cell lymphomas. The authors report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas. METHODS: Patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and untreated patients ineligible for combination chemotherapy were prescribed oral lenalidomide (25 mg daily) on Days 1 to 21 of each 28-day cycle until disease progression, death, or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The 2-stage design allows for up to 40 patients. RESULTS: At the time of this interim analysis, 24 patients were enrolled in this study, and 23 were evaluable for response. The median age was 65 years. The overall response rate was 7 (30%) of 23; all were partial responses. Two patients had stable disease for >=5 cycles. Responses were seen in anaplastic, angioimmunoblastic, and peripheral T-cell unspecified histologies. Median PFS was 96 days (range, 8-696+ days). Median OS was 241 days (range, 8-696+ days). The most common grade 4 adverse event was thrombocytopenia (33%). The most common grade 3 adverse events were neutropenia (21%), febrile neutropenia (17%), and pain not otherwise specified (17%). Rash correlated with response to therapy (P=.003). CONCLUSIONS: In patients with recurrent and refractory T-cell lymphomas, oral lenalidomide monotherapy has clinical activity, and toxicity is consistent with the known safety profile of lenalidomide. Further study of lenalidomide in these diseases is warranted. PMID- 20572047 TI - A multiplexed, particle-based flow cytometric assay identified plasma matrix metalloproteinase-7 to be associated with cancer-related death among patients with bladder cancer. AB - BACKGROUND: The current study was conducted to demonstrate the utility of a multiplexed, particle-based flow cytometric assay for the simultaneous analysis of a panel of matrix metalloproteinases (MMPs) using small volumes of plasma samples from patients with bladder cancer. In addition, the authors attempted to test the hypothesis that plasma levels of MMPs are associated with time to cancer related death. METHODS: Plasma MMP concentrations (MMP-1, -2, -3, -7, -8, -9, and -12) in 135 patients presenting with high-grade>=T1 bladder cancer were measured. Data regarding clinical and pathologic features was ascertained in a retrospective fashion. RESULTS: The median duration of follow-up was 30.4 months. At the time of analysis, 61 patients had died, including 45 (33.3%) who died of bladder cancer. Plasma MMP-12 was not measurable. For all other MMPs, the intra assay coefficient of variation varied from 6.12% to 9.82%. MMP-1, -2, -3, -8, and -9 were not found to be significantly associated with time to cancer-related death. Plasma MMP-7 levels were significantly associated with time to cancer related death after adjustment for competing clinical and pathologic features (hazard ratio [HR], 2.2; 95% confidence interval [95% CI], 1.1-4.5 [P=.022]). The 5-year median cancer-specific survival rates for those patients with MMP-7 levels above and below the median value (300 pg/mL) were 73.6% (95% CI, 60.0-83.2%) and 48.0% (95% CI, 32.5-61.9%), respectively (P=.01). CONCLUSIONS: Multiplexed, particle-based flow cytometric assay allows for the high-throughput measurement of multiple plasma or serum proteins simultaneously. By using this new technology in a cohort of patients with bladder cancer, plasma levels of MMP-7 were identified as being significantly associated with time to cancer-related death. PMID- 20572048 TI - Utility of the GeneSearch breast lymph node assay for the rapid evaluation of sentinel lymph nodes in breast cancer. AB - BACKGROUND: The potential for reducing the need for second surgery for axillary lymph node dissection (ALND) has made the intraoperative evaluation of sentinel lymph nodes (SLNs) attractive. The goal of the current study was to evaluate the clinical application of the breast lymph node (BLN) assay, a real-time reverse transcriptase-polymerase chain reaction assay for SLN metastases, by comparing this test with routine pathologic examination. METHODS: A total of 117 patients with breast cancer underwent breast surgery with SLN biopsy. Each SLN was cut in half along the plane of the longest dimension. Half of each lymph node was examined by the 2 markers of the BLN assay, mammaglobin and cytokeratin 19, and the other half was examined by hematoxylin and eosin staining (H&E) and immunohistochemical staining (IHC) for pancytokeratins. RESULTS: A total of 204 SLNs were obtained from 117 patients. H&E staining identified metastases in 31 SLNs (15.2%), and IHC staining detected metastases in 6 SLNs; 40 SLNs from 32 patients were found to be positive for metastasis using the BLN assay. The assay results were correlated with the pathologic diagnoses by H&E and IHC staining (P<.001). The sensitivity of the BLN assay compared with pathologic findings classified according to the TNM classification was 95.7% for macrometastases, 60.0% for micrometastases, and 55.6% for isolated tumor cells. CONCLUSIONS: The 2 marker BLN assay performs in a manner that is comparable to, and analyzes more tissue than, routine pathologic examination. Therefore, clinical intraoperative use of the BLN assay for SLNs may result in a reduction in the need for second surgery for ALND. PMID- 20572050 TI - Re: Madore et al. Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma. J Pathol 2010;220:392-400. PMID- 20572051 TI - Subtilisin-gamma-glutamyl transpeptidase: a novel combination as ungual enhancer for prospective topical application. AB - A feather degrading strain of Bacillus licheniformis ER-15 was isolated which also degraded alpha-keratin of hooves. A detailed analysis revealed that a novel monomeric gamma-glutamyl transpeptidase (GGT(30)), a proteolytic product of heterodimeric 67 kDa gamma-glutamyl transpeptidase (GGT(67)), assists subtilisin during its action on alpha keratin. An equimolar combination of subtilisin and GGT(30) was designated as KerN and was used as ungual enhancer for topical application. KerN was effective in releasing proteins from nail plate surface and 300 ug of enzyme could release 41 ug protein/mg of nail after 24 h treatment. Scanning electron micrograph (SEM) revealed loosening of nail matrix confirming the action of KerN on nail keratin. Drug permeation studies revealed permeation of clotrimazole through both enzymatically pretreated nail plates and also through nail plates in presence of KerN. Nearly 58% drug could be retained by nail plates after 24 h of 300 ug/mL KerN which further enhanced up to 97% by prolonging the enzyme application. The enzyme was found to be stable in presence of drug even after 72 h. Thus, KerN can be used as an additive in formulation of topical drug for onchomycosis. PMID- 20572052 TI - Impact of glutaraldehyde on in vivo colon-specific release of resveratrol from biodegradable pectin-based formulation. AB - Despite potential therapeutic efficacy of resveratrol on colitis and colorectal cancer, rapid absorption and metabolism at the upper gastro-intestinal (GI) tract prevent its clinical application. To overcome this, we attempted to develop colon specific multi-particulate calcium-pectinate (Ca-pectinate) formulations of resveratrol. However, they were unable to prevent premature drug release at the upper GI tract. Thus, glutaraldehyde (Glu) was used for further cross-linking of the pectin chains. The formulation conditions and procedure were optimized from the in vitro drug release study. The optimized formulation was subjected to in vivo pharmacokinetic study in rats and compared with the unmodified Ca-pectinate and suspension formulation of resveratrol. Spherical particles (~1 mm diameter) with high drug encapsulation were produced. Low cross-linking solution pH (1.5), minimum Glu concentration (2.5%) and cross-linking time (2 h) were crucial to exhibit colon-specific drug release. As Glu was added in the cross-linking solution, cross-linking between pectin chains and Glu occurred simultaneously during Ca-pectinate network formation, which appeared as a cost-effective formulation technique. Most importantly, the pharmacokinetic study demonstrated in vivo colon-specific drug release from the optimized formulation, while faster drug release was observed from the unmodified and suspension formulations. Hence, the developed formulation has potential to be used as colon-specific delivery system of resveratrol. PMID- 20572053 TI - Dissolution rate enhancement of parabens in PEG solid dispersions and its influence on the release from hydrophilic matrix tablets. AB - The dissolution rate of a homologous series of parabens and their dispersions in PEG 4 * 10(3) was examined. In light of these measurements, the release behavior of the substances from extended release hydrophilic matrix tablets based on PEO 5 * 10(6) was studied. Tablet release was examined for matrices comprising either a physical mixture of PEG, paraben, and PEO, or a solid solution of each paraben in PEG, incorporated in the PEO matrix. Considerable increase of the dissolution rate for the eutectic and in particular solid solution form of the parabens was observed. The hydration rate of all matrices, as well as polymer release, was the same. The release rate of methyl, ethyl, and butyl parabens in solid solution form was similar to that of their crystalline form. However, the release rate of the solid solution form of propyl paraben was higher than that of its crystalline form, especially in the initial part of the release. The results indicate that all parabens crystallized in the gel layer of the solid solution formulations upon the process of tablet dissolution. This was proposed to be an effect of differences in the dissolution and crystallization kinetics of the parabens. PMID- 20572054 TI - Evaluation of hydroxypropyl methylcellulose matrix systems as swellable gastro retentive drug delivery systems (GRDDS). AB - Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS. PMID- 20572055 TI - Prediction of bulk powder flow performance using comprehensive particle size and particle shape distributions. AB - The purpose of this study is to establish a modeling approach that can be used to predict bulk powder flowability of pharmaceutical materials from their particle size and shape distributions. To build and validate the model, 23 commonly used pharmaceutical excipients and 38 binary blends were fully characterized for their particle size and shape distributions. The particle size and shape of each sample was characterized by multiple descriptors to fully reflect their morphological characteristics. The flow properties of these materials were analyzed using the Schulze Ring Shear Tester at a fixed humidity condition. A partial least squares (PLS) approach was used to build the mathematical model. Several different modeling approaches were attempted and the best method was identified as using a combination of formulation composition and particle size and shape distributions of single-component powder systems. The PLS model was shown to provide excellent predictions of powder flow function coefficient (FFC) of up to approximately 20. The results also revealed that both particle size and shape play an important role in determining the powder flow behavior. PMID- 20572056 TI - Root colonisation by the arbuscular mycorrhizal fungus Glomus intraradices alters the quality of strawberry fruits (Fragaria x ananassa Duch.) at different nitrogen levels. AB - BACKGROUND: Arbuscular mycorrhizal fungi (AMF) increase the uptake of minerals from the soil, thus improving the growth of the host plant. Nitrogen (N) is a main mineral element for plant growth, as it is an essential component of numerous plant compounds affecting fruit quality. The availability of N to plants also affects the AMF-plant interaction, which suggests that the quality of fruits could be affected by both factors. The objective of this study was to evaluate the influence of three N treatments (3, 6 and 18 mmol L(-1)) in combination with inoculation with the AMF Glomus intraradices on the quality of strawberry fruits. The effects of each factor and their interaction were analysed. RESULTS: Nitrogen treatment significantly modified the concentrations of minerals and some phenolic compounds, while mycorrhization significantly affected some colour parameters and the concentrations of most phenolic compounds. Significant differences between fruits of mycorrhizal and non-mycorrhizal plants were found for the majority of phenolic compounds and for some minerals in plants treated with 6 mmol L(-1) N. The respective values of fruits of mycorrhizal plants were higher. CONCLUSION: Nitrogen application modified the effect of mycorrhization on strawberry fruit quality. PMID- 20572057 TI - Comparison of PCR-DGGE and PCR-SSCP analysis for bacterial flora of Japanese traditional fermented fish products, aji-narezushi and iwashi-nukazuke. AB - BACKGROUND: The bacterial flora of two Japanese traditional fermented fish products, aji-narezushi (salted and long-fermented horse mackerel (Trachurus japonicas) with rice) and iwashi-nukazuke (salted and long-fermented sardine (Sardinops melanostica) with rice bran), was analysed using non-culture-based polymerase chain reaction (PCR) denaturing gradient gel electrophoresis (DGGE) and culture-based PCR single-strand conformation polymorphism (SSCP) methods. RESULTS: Viable plate counts in aji-narezushi and iwashi-nukazuke were about 6.3 6.6 and 5.7-6.9 log colony-forming units g(-1) respectively. In the PCR-DGGE analysis, Lactobacillus acidipiscis was detected as the predominant bacterium in two of three aji-narezushi samples, while Lactobacillus versmoldensis was predominant in the third sample. By the PCR-SSCP method, Lb. acidipiscis and Lactobacillus plantarum were isolated as the predominant bacteria, while Lb. versmoldensis was not detected. The predominant bacterium in two of three iwashi nukazuke samples was Tetragenococcus muriaticus, while Tetragenococcus halophilus was predominant in the third sample. CONCLUSION: The results suggest that the detection of some predominant lactic acid bacteria species in fermented fish by cultivation methods is difficult. PMID- 20572058 TI - Isolation and physicochemical characterisation of starch from cocoyam (Colocasia esculenta) grown in Malawi. AB - BACKGROUND: The aim of this study was to determine the physicochemical properties of starches isolated from Malawian cocoyams and compare them with those of cassava and corn starches. RESULTS: The purity of the isolated starches varied from 851 to 947 g kg(-1) and pH from 4.93 to 6.95. Moisture, ash, protein, fat and amylose contents ranged from 104 to 132, 0.3 to 1.5, 3.5 to 8.4, 0.9 to 1.6, and 111 to 237 g kg(-1), respectively. Cocoyam starches gave higher potassium and phosphorus but lower calcium levels than the other starches. The shape of starch granules varied from spherical to polygonal with cocoyam starches displaying smaller-sized granules than cassava and corn starches. Cocoyam starches gave a higher wavelength of maximum iodine absorption and blue value but lower reducing capacity values than cassava and corn starches. The extent of acid hydrolysis of the starches also differed. Cocoyam starches exhibited amylopectin molecules of higher molecular weights but amylose molecules of lower molecular weights than cassava and corn starches. Cocoyam starches exhibited lower water absorption capacity and swelling power, paste clarity and viscosity but higher solubility, gelatinisation temperatures and retrogradation tendencies than cassava and corn starches. CONCLUSIONS: The physicochemical properties of native Malawian cocoyam starches vary among the different accessions and differ from those of cassava and corn starches. PMID- 20572059 TI - Metabolite profiling of doenjang, fermented soybean paste, during fermentation. AB - BACKGROUND: A fermented soybean paste known as doenjang is a traditional fermented food that is widely consumed in Korea. The quality of doenjang varies considerably by its basic ingredients, species of microflora, and fermentation process. The classification of predefined metabolites (e.g. amino acids, organic acids, sugars and sugar derivatives, and fatty acids) in doenjang samples according to fermentation was performed by using GC-FID and GC-MS data sets with the application of a multivariate statistical method. RESULTS: The predominantly produced amino acids included alanine, valine, leucine, isoleucine, proline, glutamine, phenylalanine and lysine, showing remarkable increases in amounts during the later stages of fermentation. Carbonic acid, citric acid, lactic acid and pyrogultamic acid were identified as the major organic acids. Significant amounts of erythrose, xylitol, inositol and mannitol were detected during fermentation. Regarding fatty acids, relatively higher amounts of palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid were found in the doenjang at each fermentation time point. Principal component analysis (PCA) successfully demonstrated changes in composition patterns as well as differences in non-volatile metabolites according to fermentation period. CONCLUSION: A set of metabolites could be determined representing the quality of doenjang during fermentation, and which might also be correlated with taste ingredients, flavour, nutrition, and physiology activities that are claimed to be dependent on the quality control of commercial doenjang. PMID- 20572060 TI - Vascular effects of egg white-derived peptides in resistance arteries from rats. Structure-activity relationships. AB - BACKGROUND: The vasodilator properties of several peptide sequences derived from egg white proteins were screened in mesenteric resistance arteries from Wistar Kyoto rats. For this, third-order branches of the mesenteric arteries from 6 month-old male rats were used. The vasodilator responses, with or without endothelium, to several peptides (0.1 mmol L(-1)) were analysed in an isometric myograph. Moreover, the effect of nitric oxide (NO) synthase (L-NAME, 100 micromol L(-1)) and cyclooxygenase (indomethacin, 10 micromol L(-1)) inhibitors on the vasodilator response was tested. RESULTS: The peptides Arg-Ala-Asp-His-Pro Phe-Leu, Arg-Ala-Asp-His-Pro-Phe, Arg-Ala-Asp-His-Pro, Tyr-Arg-Gly-Gly-Leu-Glu Pro-Ile-Asn-Phe, Arg-Asp-Ile-Leu-Asn-Gln and Val-Pro-Pro showed a high endothelium-dependent vasorelaxation, whereas Phe-Arg-Ala-Asp-His-Pro-Phe-Leu was only partially endothelium-dependent. The relaxation induced by Arg-Ala-Asp-His Pro-Phe-Leu, Arg-Ala-Asp-His-Pro-Phe, Arg-Ala-Asp-His-Pro, Arg-Asp-Ile-Leu-Asn Gln and Val-Pro-Pro was mainly mediated by NO, since the response was inhibited only by L-NAME, while both L-NAME and indomethacin inhibited the vasodilator response induced by Phe-Arg-Ala-Asp-His-Pro-Phe-Leu and Tyr-Arg-Gly-Gly-Leu-Glu Pro-Ile-Asn-Phe. The presence of Arg or Tyr at the N-terminal position could be related to the vasodilator activity of these compounds in this vascular bed. The well-known angiotensin-converting enzyme inhibitor captopril showed only a slight vasodilator effect. CONCLUSION: These peptides could reduce the vascular resistance and be used as functional ingredients in the prevention and/or treatment of hypertension and other associated disorders. PMID- 20572061 TI - Effect of nitrogen source in the fertilizing solution on nutritional quality of three members of the Portulaca oleracea aggregate. AB - BACKGROUND: Portulaca oleracea (purslane) is nutritious but, in addition to the essential alpha-linolenic acid, vitamin C and tocopherols, it contains undesirable oxalic acid. Knowing the effects of nitrate and ammonium on oxalate accumulation, we tested the agronomic potential of three members of the P. oleracea aggregate under various nitrogen fertilization conditions, by measuring biomass production and accumulation of fatty acids, organic acids and tocopherol in the commercial P. sativa (Pos) and two natural members: P. nitida (Pon) and P. papillato-stellulata (Pop). RESULTS: With nitrate as the sole N source, we measured differences between Pon and Pos in concentrations of the essential omega 3 fatty acid alpha-linolenic acid. Pos also gained less dry biomass under these conditions, implying a higher agronomical and nutritional value for Pon. Increasing the fertilizer ammonium concentration and reducing that of nitrate significantly decreased oxalic acid by factors of up to 1.7, 2.6 and 3.4 in Pos, Pop and Pon, respectively, significantly increased concentrations of tocopherol and malic acid, had no effect on fatty acids or ascorbic acid, but reduced biomass. CONCLUSION: In spite of the recumbent growth habit of Pon, the present findings indicate its agronomic potential. Because early flowering and seed production may be the limiting factors in purslane agriculture, growing Pon in nitrate-poor conditions might be agriculturally favorable. PMID- 20572062 TI - Composition and properties of biologically active pectic polysaccharides from leek (Allium porrum). AB - BACKGROUND: Leek (Allium porrum) is very commonly used vegetable in Bulgaria and is distinctive with high content of bioactive components. Previously we obtained five crude pectic polysaccharides from leek through consecutive extraction. Some of them appeared to be good stimulators of the immune system. Schols and Voragen investigated the composition of modified hairy regions of pectic polysaccharides isolated from leek cell walls. Samuelson et al. identified the polysaccharide structures encountered in hairy regions as bioactive. The aim of this work was to study the isolation, composition and biological activities of pectic polysaccharides from leek. RESULTS: Two pectic polysaccharides from leek were isolated through consecutive water and acid extraction. The water extractable pectin had higher polyuronic content, higher protein content and lower neutral sugar content. It was found that next to galacturonic acid they also contain glucuronic acid in ratio 9:1 for the water- and 3:1 for the acid-extractable polysaccharide. The main neutral sugar was galactose. The water-extractable pectic polysaccharide had higher molecular weight (10(6) Da) and homogeneity. It was shown that the pectic polysaccharides from leek have considerable immunostimulating activities. CONCLUSION: Leek polysaccharides have relatively high galacturonic and glucuronic acid content and are distinguished with high biological activity. PMID- 20572063 TI - Correlation of hepatic vein Doppler waveform and hepatic artery resistance index with the severity of nonalcoholic fatty liver disease. AB - PURPOSE: The study was conducted to evaluate the effect of various degrees of fatty infiltration in patients with nonalcoholic fatty liver disease on hepatic artery resistance index and hepatic vein waveform patterns. METHODS: After identification and grading of fatty infiltration, 60 patients and 20 normal healthy subjects were examined using color and spectral Doppler sonography. The level of fatty liver infiltration was ascertained and graded by biopsy in patients and excluded by MRI in controls. The patients were allocated to four study groups consecutively, until the required number was reached, according to infiltration level as follows: normal (group A), mild (group B), moderate (group C), and severe (group D). The hepatic vein waveforms were classified into the three following groups: triphasic, biphasic, and monophasic waveform. The hepatic artery resistance index was calculated as the mean of three different measurements. RESULTS: The incidence of monophasic and biphasic hepatic vein waveform was 2 (10%) for group B, 11 (55%) for group C, 16 (80%) for group D, and none for group A. The difference in the distribution of triphasic Doppler waveform pattern between the patients and the control group was significant (p < 0.001). Hepatic artery resistance index was 0.81 (+ or - 0.02), 0.78 (+ or - 0.03), 0.73 (+ or - 0.03), and 0.68 (+ or - 0.05), respectively, in groups A, B, C, and D and was significantly different between groups (p < 0.001). CONCLUSION: As the severity of nonalcoholic fatty infiltration increases, the incidence of abnormal hepatic vein waveforms increases and hepatic artery resistance index decreases. PMID- 20572064 TI - Three-dimensional ultrasound inversion rendering technique facilitates the diagnosis of hydrosalpinx. AB - PURPOSE: To test the utility of three-dimensional (3D) ultrasound (US) inversion rendering technique in the evaluation of fluid-distended fallopian tubes. METHODS: Fifty-two patients with fluid-filled adnexal masses suspected of being abnormal fallopian tubes were scanned by two-dimensional and 3D transvaginal ultrasound (TVUS). Six patients had bilateral disease. The acquired volumes were then "inverted" to display a cast-like appearance of the fluid-filled structures. The ipsilateral ovaries were identified in all patients. Five patients had acute tubal disease. RESULTS: Fifty-two of the 58 inversion renderings yielded acceptable images of hydrosalpinges. Only in four patients were the two dimensional images more informative than the 3D-rendered and inverted views. In nine patients adjacent corpora lutea, ovarian cysts, and follicles within normal ovaries were also identified, but appeared separate from the fluid-filled tubes. The tubes in the patients with acute disease were all successfully inverted. CONCLUSIONS: The 3D inversion technique is a simple and effective way to render fluid-filled spaces, which may be tortuous and follow various directions. The rendered images increased the confidence in diagnosing hydrosalpinx. PMID- 20572065 TI - Ultrasound training for medical students and internal medicine residents--a needs assessment. AB - PURPOSE: While sonography has been a mainstay of certain medical specialties, such as obstetrics and gynecology, internal medicine has been slower to integrate this technology into practice. No standardized training in sonography exists for either medical students or internal medicine residents, and little is known about the current competency and utilization of ultrasound among these groups. The goal of this article is to examine the present state of ultrasound education among internal medicine residents and medical students at a major university hospital. METHODS: Third-year medical students from the University of Illinois at Chicago and senior medicine residents from University of Illinois at Chicago and Northwestern University were invited to complete a Likert-type survey regarding their attitudes, competence, and interest in ultrasound, the nature of previous training, and areas where incorporation of ultrasound would be useful. RESULTS: One hundred sixty-three students and 40 residents participated (81.8% response rate). Students and residents generally felt incompetent in the use of ultrasound; objective competency in the resident group, as evaluated by an emergency physician certified by the American College of Emergency Physicians, was equally low. However, interest in additional training was high. Nearly 50% of the respondents had no prior sonography training; however, those with previous training rated it highly. Areas in which sonography was most sought-after include central line placement, paracentesis, and thoracentesis. CONCLUSIONS: There is a clear desire for training in sonography among the medical students and internal medicine residents surveyed. As ultrasound is further integrated into clinical practice, students and residents would strongly benefit from formal didactic and hands-on training in the modality. PMID- 20572066 TI - Contrast-enhanced sonography-guided radiofrequency ablation for the local recurrence of previously treated hepatocellular carcinoma undetected by B-mode sonography. AB - BACKGROUND.: The purpose of this study was to assess the usefulness of contrast enhanced sonography (CEUS) with Sonazoid to demonstrate local recurrence of hepatocellular carcinoma previously treated with radiofrequency ablation (RFA) and not seen on conventional sonography, prior to repeat RFA. METHODS.: This study included 16 cirrhotic patients with 17 cases of hypervascular locally recurrent hepatocellular carcinoma found by contrast-enhanced multidetector row CT (MDCT) but not seen on noncontrast sonography. We used Kupffer-phase imaging and vascular-phase imaging after re-injection. The morphologic patterns of local recurrence detected on CEUS were compared with those on MDCT. We performed repeat RFA guided by CEUS using Kupffer-phase imaging after re-injection. RESULTS.: We were able to detect on CEUS the location of all local recurrences with positive enhancement after re-injection. The morphologic patterns of local recurrence on CEUS were in concordance with those found on MDCT in all lesions. Repeat percutaneous RFA was successfully performed in all lesions. CONCLUSIONS.: The CEUS appearance of local recurrences correlated well with those on MDCT. A wider use of CEUS to guide repeat of percutaneous RFA may be possible with Sonazoid. PMID- 20572067 TI - Sonographic measurement of uterus and ovaries in premenarcheal healthy girls between 6 and 13 years old: correlation with age and pubertal status. AB - BACKGROUND: To provide normal references of sonographic uterine and ovarian size in premenarcheal healthy girls aged 6-13 years in different stages of puberty. METHODS: Two hundred forty girls were enrolled into the study (mean age +/- SD, 9.5 +/- 1.7 years [range, 6-13.5 years]). Pubertal status was classified according to Tanner staging. All subjects underwent pelvic sonographic examination for the measurement of uterine volume, body and cervical length, anteroposterior diameter of fundus, body, and cervix, ovarian volume, and both right and left prominent follicular diameter. RESULTS: A gradual increase with age was observed in all uterine and ovarian measurements. Both uterine and ovarian parameters were significantly correlated to age, height and weight, and stages of puberty. Uterine volume was <3.5 cm(3) in 98% of prepubertal girls, and in stage 2 it was significantly more than in stage 1 (3 +/- 3.2 versus 1.7 +/- 1.7, respectively) (p < 0.001). Uterine body length was also significantly greater in stage 2 than stage 1 (17.5 +/- 4.5 versus 14.6 +/- 3.3, respectively) (p < 0.001). CONCLUSION: The reference values for uterus and ovaries were determined in healthy girls. There is a progressive increase in size of internal female genitalia in relation to age, height, weight, and puberty. Uterine volume and body length presented the best correlation with age and stage of puberty. PMID- 20572068 TI - Distribution of human papillomavirus types in the anogenital tract of females and males. AB - Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross-sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV-6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV-16 (7%), while HPV-16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV-6. In addition to HPV-16, HPV-58, HPV-33, HPV-31, and HPV-56 were the carcinogenic types detected most commonly and were significantly associated with high-grade squamous intraepithelial cervical lesions, while HPV-53 and HPV-66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV-6 and HPV-11 infection, and, less frequently, with other types, like HPV-54, HPV-62, and HPV-66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites. PMID- 20572069 TI - Genotype X/C recombinant (putative genotype I) of hepatitis B virus is rare in Hanoi, Vietnam--genotypes B4 and C1 predominate. AB - There are eight known genotypes of hepatitis B virus, A-H, and several subgenotypes, with rather well-defined geographic distributions. HBV genotypes were evaluated in 153 serum samples from Hanoi, Vietnam. Of the 87 samples that could be genotyped, genotype B was found in 67 (77%) and genotype C in 19 (22%). All genotype C strains were of subgenotype C1, and the majority of genotype B strains were B4, while a few were B2. The genotype X/C recombinant strain, identified previously in Swedish patients of indigenous Vietnamese origin, was found in one sample. This variant, proposed to be classified as genotype I, has been found recently also by others in Vietnam and Laos. The current study indicates that the genotype X/C recombinant may represent approximately 1% of the HBV strains circulating in Vietnam. PMID- 20572070 TI - Allele-specific conventional reverse-transcription polymerase chain reaction as a screening assay for discriminating influenza a H1N1 (H275Y) oseltamivir-resistant and wild-type viruses. AB - In early 2008, a sudden increase in oseltamivir (Tamiflu)-resistant influenza A H1N1 viruses was reported from several European countries. This resistant virus has spread globally and accounted for more than 95% of H1N1 viruses isolated in the following influenza season. A continuous close monitoring on the prevalence of this resistant virus is necessary to rationalize the choice of antiviral agents. The resistance of this novel strain to oseltamivir is conferred by an amino acid substitution from histidine to tyrosine at position 275 (H275Y) of the neuraminidase protein. This study developed and evaluated allele-specific conventional reverse-transcription polymerase chain reaction (cRT-PCR) assays to provide a simple, rapid, and low-cost option for discriminating oseltamivir resistant influenza A H1N1 (H275Y) mutant from wild-type viruses. The evaluation was based on 90 nasopharyngeal aspirate specimens collected before, during the initial phase and at the peak of emergence of resistance. Thirty-six (40%) of these specimens were H275Y mutant, whereas the other 54 (60%) were wild-type viruses as confirmed by sequencing of the neuraminidase gene. When applied directly on the 90 nasopharyngeal aspirate specimens, the allele-specific cRT-PCR assays achieved an unequivocal discrimination for 82 (91%) specimens. Further improvement in performance is expected when applied to cell culture isolates with a higher viral titer. These allele-specific cRT-PCR assays can be a simple, low cost option for large-scale screening of influenza isolates. PMID- 20572072 TI - Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation. AB - The significance of detection of herpes viruses in respiratory secretions of critically ill patients is controversial. The study aim was to determine the prevalence of herpes virus DNA in respiratory secretions in patients on artificial ventilation. Respiratory secretions taken thrice weekly from 174 patients in a tertiary center intensive therapy unit (ITU) were tested for herpes simplex virus (HSV) by nested PCR. Samples from 61 patients in ITU for 4 days or more were also tested for Epstein Barr Virus (EBV) and cytomegalovirus (CMV) using real-time PCR. HSV positivity increased with ITU stay with 18.6% admission samples positive, 32.5% day 2-5 samples, and 65.9% day 6-39 samples. Being HSV positive on admission did not influence mortality (9/27, 33.3% vs. 38/118, 32.2%) however, subsequently, mortality of those negative but becoming positive was higher than in those remaining negative (10/35, 29% vs. 5/24 21%). At least one sample was EBV positive in 61% and CMV positive in 19% of patients tested. Of 63 patients tested for all three viruses, 4 were positive for three viruses, 23 patients for two viruses, 24 for one virus and 12 were negative for all the above viruses. Detection of HSV, EBV and CMV is common in ITU patients. Becoming HSV positive while in ITU may increase mortality. PMID- 20572073 TI - Modeling seasonal variation in rotavirus hospitalizations for use in evaluating the effect of rotavirus vaccine. AB - Every year rotavirus epidemic repeats in cooler months of the year in temperate countries, but the size of the epidemic may often vary. Such seasonal variation needs to be considered when the effect of rotavirus vaccine is predicted before vaccine introduction or it is evaluated after vaccine introduction. A computer program based on a stochastic decision tree model was developed to produce stochastic variation, which was used as a proxy for seasonal variation, in the number of rotavirus hospitalizations. When the model was applied to a hypothetical community with a birth cohort of 1,000 children in Japan, it predicted the occurrence of up to 29% of stochastic variation from the average number of rotavirus hospitalizations. Then, the model was applied for use in evaluating the effect of rotavirus vaccine in two different scenarios regarding vaccine use in the community: a scenario where rotavirus vaccine was introduced only into the private sector, and another where it was incorporated into the universal immunization program. In the former scenario, an average of 23% reduction in the number of rotavirus hospitalizations was predicted, but this level of reduction would be obscured due to seasonal variation. In the latter scenario, an average of 74% reduction was predicted, which would be beyond seasonal variation. This model will be useful to inform stakeholders and policymakers how vaccine introduction will change the burden of rotavirus disease under different scenarios of vaccine implementation. PMID- 20572071 TI - Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam. AB - To identify hepatitis C virus (HCV) transmission routes among injection drug users in Northern Vietnam, plasma samples were collected from 486 drug users in Hai Phong. Plasma viral RNA was extracted from 323 (66.5%) samples that were positive for anti-HCV antibodies. Portions of the HCV 5'-untranslated (5'UTR) Core and NS5B genes were amplified by reverse-transcriptase polymerase chain reaction, sequenced directly, and genotyped in 194 and 195 specimens, respectively. Both regions were genotyped in 137 specimens. In the 5'UTR-Core region, genotype 6a was predominant (32.5%), followed by genotype 1a (23.7%), genotype 1b (20.6%), and genotype 6e (14.4%). In the NS5B region, genotype 1a was predominant (42.6%), followed by genotype 1b (24.1%), genotype 6a (14.4%), genotype 3b (7.2%), and genotype 6e (5.1%). Of the 137 specimens with both regions genotyped, 23 (16.8%) showed discordant genotyping results between the two regions, suggesting possible recombination and/or dual infection. Phylogenetic analysis revealed close associations between Hai Phong strains and strains from Southern China: the Yunnan province for genotype 3b; the Guangxi province for genotype 6e; the USA for genotype 1a; and Southern Vietnam for genotypes 1a and 6e. The human immunodeficiency virus (HIV) infection rate among HCV-infected injection drug users was 52.6-55.4% and did not differ significantly by HCV genotype. Most drug users infected with HIV-1 [98.8% (171/173)] were co infected with HCV. These results suggest multiple routes of HCV transmission among injection drug users in Northern Vietnam that may also be HIV transmission routes. PMID- 20572074 TI - Comparison of the levels of human herpesvirus 6 (HHV-6) DNA and cytokines in the cerebrospinal fluid and serum of children with HHV-6 encephalopathy. AB - Primary human herpesvirus-6 (HHV-6) infection is a common cause of acute sporadic encephalopathy in Japanese children. Occasionally, HHV-6 is not detected in the cerebrospinal fluid (CSF) of patients with encephalopathy, for example, in those with focal viral encephalitis, such as herpes simplex viral encephalitis. This indicates that HHV-6 encephalopathy is caused by an indirect mechanism, although this is not fully understood. HHV-6 DNA, cytokines (interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor-alpha, interferon-gamma), and matrix metalloproteinase-9 were quantitated in both the CSF and serum of 13 patients with HHV-6 encephalopathy during the acute phase of the disease. HHV-6 DNA was detected in the CSF of seven patients with HHV-6 encephalopathy. The viral DNA concentration was significantly higher in serum than in CSF (mean 1.64 x 10(4) vs. 5.70 x 10(1) copies/ml; P = 0.003). The lack or low level of viral DNA in the CSF samples suggests that direct invasion of the central nervous system by HHV-6 is not the main cause of encephalopathy. Additionally, the IL-10 concentration was significantly higher in serum than in CSF (P < 0.001), whereas there was no significant difference in IL-6 levels between the CSF and serum samples. Interestingly, the IL-8 concentration was significantly higher in CSF than in serum (P = 0.038). The distribution of these cytokines differed between CSF and serum. The high CSF concentration of IL-8 could play an important role in the pathogenesis of encephalopathy. PMID- 20572075 TI - Characterization of human papillomavirus infection in north Taiwan. AB - The detection of human papillomavirus (HPV) is very important for the evaluation of preventative strategies for cervical cancer. The major objective of this study was to characterize the prevalence of different genotypes of HPV in north Taiwan to contribute to the epidemiological knowledge of HPV infections. Papanicolaou (Pap) cervical smears were collected from 10,543 women aged between 14 and 87 years. The polymerase chain reaction (PCR) and DNA array hybridization techniques were used to genotype 51 different HPV strains. HPV was detected in 1,577 women, which gave an overall HPV prevalence rate of 15%. Forty-eight different genotypes were found in these patients, which included 9.7% that were high-risk HPV (HR HPV) genotypes. The most common types of HR-HPV in patients, in descending order of frequency, were HPV 52, 16, 58, 56, 39, 51, 18, 68, 31, 33, 59, 45, and 35. HPV 52 was the most frequent type in every age group. The four most common HR-HPV types were found in 56.6% of the patients infected with HR-HPV. In cases that were infected with multiple HPV genotypes, 69.2% had at least one HR-HPV genotype. The rate of infection with HR-HPV was higher in the younger age groups than the older ones. In conclusion, 48 HPV genotypes were identified from a large study of cervical screening samples and the prevalence of HPV genotypes in different age groups was very diverse. The formulation of a public health strategy for HPV vaccination should take into account the prevalence of various HR-HPV/LR-HPV genotypes. PMID- 20572076 TI - Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda. AB - Commercially available rapid strip assays (RSAs) for hepatitis B surface antigen (HBsAg) are used for most routine clinical testing in sub-Saharan Africa. This study evaluated the validity of RSA and a more sophisticated enzyme immunoassay (EIA) with confirmation by nucleic acid testing (NAT) in hospitalized patients in Uganda. Sera from 380 consecutive patients collected and tested for HBsAg and anti-HIV in Kampala, Uganda by RSA were sent frozen to Dallas for EIA including HBsAg, total anti-hepatitis B core, hepatitis B e antigen, and anti-HIV. NAT was performed on all HBsAg-positives and on a random sample of 102 patients that were HBsAg-negative by both assays. Overall, 31 (8%) were HBsAg positive by RSA while 50 (13%) were HBsAg-positive by EIA; 26 were concordant between the two assays. Of 55 HBsAg-positive patients, nearly all showed detectable serum hepatitis B virus (HBV) DNA by bDNA (46) or PCR (4) assay. The 26 patients who were HBsAg positive by both EIA and RSA had significantly higher median serum HBV DNA levels than the 24 patients who were HBsAg positive by EIA alone. An additional 12/102 (12%) HBsAg negative patients had very low serum HBV DNA levels by NAT. Several differences in expected results of serologic testing were observed in this large series of African patients. RSA HBsAg testing is less sensitive than EIA; even EIA failed to detect all HBV DNA positive sera. A more complex testing protocol than RSA alone will be needed in Africa to improve patient care. PMID- 20572077 TI - FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells. AB - The hallmark of the dengue hemorrhagic fever/dengue shock syndrome is hematologic abnormality. The pathogenesis of dengue hemorrhagic fever/dengue shock syndrome remains unknown. Our work showed that the dengue virus serotype-2 induced apoptosis in human umbilical vein endothelial cells. Fas (CD95), Tumor Necrosis Factor receptors, and Tumor Necrosis Factor-related apoptosis-inducing ligand receptors are the most common death receptors, which can induce apoptosis. Compared with the untreated human umbilical vein endothelial cells, Fas expression was increased both in the mRNA level and on the surface of infected human umbilical vein endothelial cells. FasL was expressed at similar levels on human umbilical vein endothelial cells over a course of dengue virus serotype-2 infection, but the expression in mRNA level was increased in infected human umbilical vein endothelial cells. It is possible that there is soluble FasL secreted from human umbilical vein endothelial cells in the supernatant. Tumor Necrosis Factor-related apoptosis-inducing ligand receptor 1 and Tumor Necrosis Factor receptors 1-2 were constantly very low, whereas Tumor Necrosis Factor related apoptosis-inducing ligand receptors 2-4 decreased after dengue virus serotype-2 infection. This result suggested that dengue virus serotype-2 may inhibit Tumor Necrosis Factor-related apoptosis-inducing ligand receptors-induced apoptosis. The apoptotic rates in human umbilical vein endothelial cells were decreased upon the addition of caspase family inhibitors. In addition, activated caspase 8 and caspase 3 were also observed by Western blot following dengue virus serotype-2 infection. Thus, it is shown that the Fas/FasL pathway may participate in dengue virus-induced apoptosis of vascular endothelial cells in vitro. PMID- 20572078 TI - Poor performance of hepatitis C antibody tests in hospital patients in Uganda. AB - Most hepatitis C testing in Uganda is performed using commercial rapid strip assays (RSA) to detect antibodies to hepatitis C virus (anti-HCV), rather than enzyme immunoassays (EIA). The prevalence of hepatitis C antibodies in a Ugandan hospital population was determined using both methods to test their accuracy using nucleic acid testing (NAT) as a reference. Sera from 380 consecutive hospitalized Ugandan patients were tested for anti-HCV using an RSA in Uganda, with subsequent automated third-generation EIA testing in the United States, followed by NAT. Recombinant immunoblot assays (RIBA) were used as a supplementary test to detect anti-HCV epitopes. Overall, anti-HCV was detected in 48/380 (13%) by one or both antibody tests. Anti-HCV was detected in 19 (5.0%) patients by RSA and in 33 (8.7%) patients by EIA; only four patients were anti HCV positive by both methods. Fourteen of the 48 anti-HCV positive patients had detectable serum HCV RNA, 7 each by bDNA assay or by PCR. RSA detected only 7 of 14 HCV RNA positive sera. Of 29 RNA negative but anti-HCV positive patients tested by RIBA, only two were anti-HCV positive; 27 were anti-HCV negative or indeterminate. Anti-HCV testing by RSA and/or EIA was neither sensitive nor specific for detection of ongoing HCV infection in hospitalized Ugandan patients. Our findings underscore the importance of confirmatory nucleic acid testing, which, despite its increased cost, appears essential to manage African patients with HCV. PMID- 20572080 TI - Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital. AB - There are few data describing the comprehensive identification in and influence of newly identified respiratory viruses on asthma exacerbations. Most studies focus on inpatients. In this preliminary study, the point prevalence and the associations of picornavirus species described recently and human bocavirus (HBoV) with the recovery from exacerbations in non-hospitalized asthmatic children (median age 5.1 years) were examined. Human rhinoviruses (HRVs) were present in 52.6% of specimens, HBoV-1 was in 7.7%. Viral co-detections occurred in 25.6% of children and were associated (P = 0.04) with lower asthma quality of life scores upon presentation than were single viral detections. The undifferentiated presence or absence of virus did not influence the severity of asthma or recovery however when virus species were examined individually, specific clinical associations emerged. HRV species C (HRV-Cs) were the viruses most frequently detected as single virus detections. Among 41 genotyped HRVs, more HRV-Cs (n = 23) were identified than HRV-As (n = 16) however HRV-A detection was associated (P = 0.01) with worse asthma symptoms and cough for longer than was HRV-C detection. Larger, PCR-based studies are required to elucidate further the true impact of HRV species in childhood asthma exacerbations of both hospitalized and non-hospitalized cohorts. PMID- 20572079 TI - Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C. AB - The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy. PMID- 20572081 TI - Adenovirus genome in the placenta: association with histological chorioamnionitis and preterm birth. AB - Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi-square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy-one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4-5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty-seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus-positive placentas compared to preterm adenovirus-negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus-positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth. PMID- 20572082 TI - Low level myocardial parvovirus B19 persistence is a frequent finding in patients with heart disease but unrelated to ongoing myocardial injury. AB - While myocardial parvovirus B19 (B19V), aside from enteroviruses (EV) and adenoviruses (ADV), has recently been found often in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC), the pathogenetic significance of B19V genomes in those patients has not yet been sufficiently elucidated. In the present study, left ventricular endomyocardial biopsies from 24 patients with left ventricular ejection fraction (LVEF) below 55% due to IDC, and tissue from the right atrial appendage of 10 control patients undergoing bypass surgery with normal LVEF (>55%) were investigated for B19V, ADV, and EV genomes by specific nested polymerase chain reaction (PCR), by real time PCR or by reverse transcription PCR, respectively. The myocardial tissue samples from the 10 controls were analyzed each in three different virological laboratories for B19V. In the IDC group, the frequency of the myocardial virus genomes found in 54% (13/24) of the patients was as follows: B19V: 50% (12/24), EV: 8% (2/24), including one patient with B19V and EV, and ADV: 0% (0/24). For comparison, the prevalence of B19V genomes was between 30% and 60% in the control group as detected in three different laboratories, but all these control subjects were EV- and ADV-negative. The number of B19V gene copies, however, was very low and similar both in the IDC and control group. In the majority of patients myocardial B19V persistence was associated with a low virus load irrespective of the underlying heart disease so that it may be of no importance in the pathogenesis of IDC. PMID- 20572083 TI - Atypical manifestations of hepatitis A infection: a prospective, multicenter study in Korea. AB - The clinical outcome of symptomatic hepatitis A and the incidence and clinical characteristics of atypical presentation of hepatitis A were studied using prospective, multicenter design. The atypical presentation included delayed anti hepatitis A virus (HAV) immunoglobulin M (IgM) seroconversion defined as positive anti-HAV IgM on the repeated test within 7 days of hospital admission after the initially negative result, prolonged cholestasis, and acute kidney injury (AKI). A total of 595 patients with symptomatic hepatitis A requiring hospital admission were enrolled prospectively from September 2006 to August 2008 in four major hospitals in a Korean city with a population of approximately 1 million. Clinical outcomes of symptomatic hepatitis A showed a case fatality rate of 0.2%, and fulminant hepatitis in 0.5%. Delayed anti-HAV IgM seroconversion was found in 6.4%, and was significantly associated with shorter intervals from symptom onset to hospital admission, higher body mass index, and lower alanine aminotransferase (ALT) level at admission. Prolonged cholestasis was found in 4.7% of patients, and could be predicted by preexisting chronic hepatitis B viral infection, prolonged prothrombin time, and higher total bilirubin level. AKI was complicated in 1.5%, which could be predicted by lower albumin level, higher ALT level, and higher white blood cell (WBC) count. More than half of the patients required hemodialysis. Substantial occurrence of delayed anti-HAV IgM seroconversion, prolonged cholestasis, and AKI was confirmed with various predictable factors, which could be helpful for accurate diagnosis and management of hepatitis A patients. PMID- 20572084 TI - Respiratory syncytial virus and human rhinoviruses are the major causes of severe lower respiratory tract infections in Kuwait. AB - Respiratory infections are very common in Kuwait, yet little is known about the cause of severe lower respiratory tract infections. This study was designed to investigate the viral cause of lower respiratory tract infections using sensitive molecular methods. PCR was applied to investigate 10 respiratory viruses in respiratory samples from 1,014 patients aged between 3 days to 76 years with acute lower respiratory tract infections. Of the 1,014 patients with lower respiratory tract infections, 288 (28.4%) had a viral infection. One hundred fifty-five (53.8%) presented with bronchiolitis, 100 (43.7%) with pneumonia, and 33 (11.5%) with croup. One hundred six (36.8%) and 99 (34.4%) patients had evidence of respiratory syncytial virus and human rhinoviruses infections, respectively. Adenoviruses were detected in 44 (15.2%) patients, while influenza A virus in 21 (7.3%) patients. The majority of respiratory syncytial virus infections (84%) were among patients aged <1 year. Similarly, of the 99 patients infected by human rhinoviruses, 50 (50.5%) were also among this age group. In contrast, most of influenza A virus infections, 12 of 21 (57.1%), were among patients aged over 16 years. Parainfluenza virus-2 and human coronaviruses were not detected in any of the patients' samples. Over the 3-year period, most of the hospitalized patients were seen during the autumn and winter months from October through March. These data show that respiratory syncytial virus and human rhinoviruses may be the major causes of lower respiratory tract infections in children admitted to hospital in Kuwait. PMID- 20572085 TI - Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit. AB - Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty-three CMV seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV-specific T-cell immunity was assessed by intracellular cytokine staining. Plasma TNF-alpha levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Clearance of CMV DNAemia preceded that of CMV DNA in TA in some episodes. Peak CMV DNA levels were significantly higher in TA than in PL (P = 0.02). CMV reactivation developed in the presence of CMV-specific T cells. Termination of CMV reactivation was associated with an expansion of functional CMV-specific T cells. Plasma levels of TNF-alpha did not allow for the prediction of the occurrence of CMV reactivation. CMV-specific T-cell immunity is preserved in most critically ill patients experiencing CMV reactivation. Analysis of respiratory specimens is imperative for an optimal monitoring of CMV reactivation in this setting. PMID- 20572087 TI - Clinical use of liver biopsy for the diagnosis and management of inactive and asymptomatic hepatitis B virus carriers in Bangladesh. AB - Patients with inactive chronic hepatitis B virus (HBV) infection are assumed to be free from liver disease. Accordingly, antiviral drug treatment is not recommended for these patients. However, the extent of liver damage in these patients has not been evaluated fully. The aim of this study was to evaluate the extent of liver damage in patients with inactive HBV. Liver biopsy was conducted in 141 inactive HBV carriers [HBeAg-negative, low levels of HBV DNA (or= 7) were detected in 36 of 141 (26%) patients. Seventeen patients had a severe degree of hepatic fibrosis (HAI fibrosis score HAI-F >or= 3). A total of 10 patients had both considerable necroinflammation (HAI-N1>or=7) and severe fibrosis (HAI-F >or=3). All 10 patients with significant hepatic inflammation and fibrosis were male and older than 25 years. However, all were HBeAg-negative and expressed low levels of HBV DNA and normal ALT levels. The study demonstrates that features of liver damage were present in a considerable number of the patients. Assessment of liver biopsy specimens in a larger cohort of inactive HBV carriers is necessary to establish management guidelines for such patients. PMID- 20572088 TI - Surveillance of norovirus infections in the state of Rio De Janeiro, Brazil 2005 2008. AB - A 4-year (2005-2008) norovirus (NoV) surveillance study was conducted in the state of Rio Janeiro, Brazil, to demonstrate the role of these viruses in outbreaks and sporadic cases of acute gastroenteritis. A cohort of 1,687 fecal samples was obtained from patients with gastroenteritis; 324 were rotavirus positive. Of the remainder 1,363 rotavirus-negative samples, 1,087 samples were tested for NoV RNA in this study. The study enrolled 267 outpatients from Municipal Public Health Centers and 820 inpatients, whose samples were obtained by active surveillance in Public Hospitals. Fecal samples were tested by reverse transcription (RT) followed by polymerase chain reaction (PCR) using the MON 431 434 set of degenerate primers for NoV GI and GII detection, and there were 35.1% (381/1,087) positive samples for NoV, consisting of 30.2% (248/820) and 49.8% (133/267) from inpatient and outpatient, respectively. Children infected by NoV had significantly more frequent mucus in feces, vomiting and fever. No seasonal pattern in NoV infections was observed in patients admitted to hospital; however, two peaks of NoV infections were observed from ambulatory cases, suggesting that there was an occurrence of outbreaks in those time periods. Molecular characterization revealed GII to be the most prevalent genogroup, totaling 96.3% (104/108) of all sequences analyzed, and GII.4 was the genotype detected most frequently (80.7%), followed by GII.6, 3, 14, 7, and 8. Two GI strains, GI.2 and GI.3, were also observed. The number of outbreaks and sporadic cases described in this study highlights the need to implement diagnosis of NoV in surveillance laboratories. PMID- 20572086 TI - Molecular epidemiological study of hepatitis B virus among migrant workers from Cambodia, Laos, and Myanmar to Thailand. AB - Although hepatitis B virus (HBV) infection is endemic in Southeast Asia, molecular epidemiological data on HBV circulating in some countries are limited. The aims of this study were to evaluate the seroprevalence of HBV and its genetic variability among migrant workers from Cambodia, Laos, and Myanmar in Thailand. Sera collected from 1,119 Cambodian, 787 Laotian, and 1,103 Myanmarese workers were tested for HBsAg. HBV DNA was amplified and the pre-S/S region was sequenced for genotyping and genetic mutation analysis. HBsAg was detected in 282 (9.4%). The prevalence of HBsAg among migrant workers from Cambodia, Laos, and Myanmar was 10.8%, 6.9%, and 9.7%, respectively. Of 224 subjects positive for HBV DNA, 86% were classified as genotype C (99% were sub-genotype C1) and 11.6% were genotype B (30.8%, 34.6%, and 30.8% were sub-genotypes B2, B3, and B4, respectively). Various point mutations in the "a" determinant region were detected in approximately 18% of these samples, of which Ile126Ser/Asn was the most frequent variant. Sequencing analysis showed that 19.1% of samples had pre-S mutations, with pre-S2 deletion as the most common mutant (7.7%) followed by pre S2 start codon mutation (3.8%) and both pre-S2 deletion and start codon mutation (3.3%). High prevalence of HBV infection (approximately 7-11%) was found among migrant workers from Cambodia, Laos, and Myanmar, which may reflect the current seroprevalence in their respective countries. The data also demonstrated that HBV sub-genotype C1 was the predominant strain and various mutations of HBV occurring naturally were not uncommon among these populations. PMID- 20572089 TI - Young age a predictor of weak reactivity in a rapid antibody test in infants infected with HIV. AB - In a resource-constrained African setting, children suspected of being infected with HIV are often screened with rapid antibody tests prior to definitive diagnosis with viral genome detection. It has previously been shown that a rapid antibody assay such as the Capillus HIV-1/HIV-2 test may have a high false negative rate in infants. In this study CD(4) (+) count and percentage, HIV-1 viral load, antigen-specific reactivity, and age was explored as predictors of negative or low antibody reactivity by this assay. Young age was found to be the only factor associated significantly with low antibody reactivity. This phenomenon appeared to be specific to HIV since no such age association was found for antibody reactivity to tetanus toxoid. Rapid assays only validated in adults should therefore be used with utmost caution in young infants since this may lead to high rates of false-negative results. PMID- 20572090 TI - Correlation of HTLV-1 Tax genetic diversity with HTLV-1 associated myelopathy/tropical spastic paraparesis progression and HTLV-1a genotypes in an HTLV-1 endemic region in Argentina. AB - The oncoprotein Tax was characterized genetically from a large cohort of human T cell lymphotropic virus type 1 (HTLV-1) seropositive individuals from the most endemic region of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 infection in Argentina, the province of San Salvador de Jujuy. Sixteen HAM/TSP patients and 47 HTLV-1 healthy carriers were evaluated. Six Tax genetic polymorphisms were identified and observed in 70.8% of healthy carriers and 62.5% of HAM/TSP patients. Tax genetic polymorphisms were not associated with clinical status but A8344C polymorphism statistically provide a borderline protective effect of HAM/TSP outcome. Nucleotide diversity in healthy carriers was 0.00549, whereas HAM/TSP virus population revealed a low diversity of 0.00379, suggests a positive selection for Tax protein conservation in this group. It is concluded that tax genetic polymorphisms do not increase the risk of developing HAM/TSP in this endemic region. However, in spite of the low prevalence of HTLV-1aB genotype, statistical analysis revealed an important correlation of tax genetic signatures with HTLV-1aA trans-continental subgroup. PMID- 20572092 TI - Quantitative and qualitative assay of rubella IgA antibody in breast milk. AB - Breast milk contains immunological factors, such as IgA antibody, which help to prevent infectious diseases. A total of 197 paired samples of colostrum and breast milk was collected from postpartum mothers in Gunma City, Japan, and examined for anti-rubella IgA antibody by enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB). The anti-rubella virus IgA ranged from 0.5 to 78.5 U/ml with a mean of 6.05 U/ml and a median of 3.6 U/ml in colostrum, and from 0.5 to 32.7 U/ml with a mean of 2.74 U/ml and a median of 2 U/ml in milk. The differences between the means of titers of total IgA and anti-rubella virus IgA in colostrum and in milk were significant statistically. The levels of anti rubella virus IgA in both colostrum and breast milk correlated positively with the anti-rubella virus hemagglutination inhibition (HI) titers in the sera of mother, indicating that the levels of these different classes of antibodies correlated. Based on WB, anti-rubella virus IgA in both colostrum and breast milk reacted with the rubella viral protein E1 and C, but not with the E2 protein. PMID- 20572091 TI - Testing for human papillomavirus and measurement of viral load of HPV 16 and 18 in self-collected vaginal swabs of women who do not undergo cervical cytological screening in Southern France. AB - Self-sampling using vaginal swabs could be a valuable alternative to screen for cervical cancer for women who do not attend regular cytological screening. The aim of this study was to determine the prevalence of high and low-risk HPV types and of HPV type 16 and 18 DNA load in self-collected vaginal swabs from 35- to 69 year-old Southern French women of low socioeconomic level or migrant populations who do not attend regular cervical screening. A good concordance (93.1%) was found between cervical brush and vaginal swabs in 29 samples. Self-collected vaginal swabs were examined from 120 women. HPV infection was found in 28 women (23.3%; median age 48 years), 17 (14.1%) of whom harbored high-risk HPV types. HPV type 16 was the high risk type found most frequently, followed by types 53, 31, 18, 58, and 66. The low-risk type detected most frequently was HPV type 6, followed by types 61, 70, and 81. The mean HPV 16 and 18 load was 6.3 log(10) copies/10(6) cells and 2.4 log(10) copies/10(6) cells, respectively. These results suggest that vaginal self-swabs can be a reliable tool for cervical cancer screening in non-attending and inadequately screened elderly women. PMID- 20572093 TI - Maternal satisfaction with postpartum nursing centers. AB - We explored predictors of women's satisfaction with postpartum nursing centers, which have become popular in Taiwan in recent years. After completing a consent form and demographic questionnaire, 401 women from different centers identified by proportional stratified quota sampling completed four questionnaires over the telephone after their fourth week postpartum. A high level of social support and low level of postpartum stress significantly predicted their satisfaction with the postpartum nursing centers. Future studies will be needed to determine whether, compared to traditional care at home, the postpartum nursing centers can help ease mothers' transition to parenthood and improve their childcare competence. PMID- 20572094 TI - Strengthening data quality in studies of migrants not fluent in host languages: a Canadian example with reproductive health questionnaires. AB - The need to collect health data from refugees and asylum seekers often requires that questionnaires be translated. Verifying the clarity, meaning, and acceptability of translated questionnaires with monolingual persons, individuals from the target population who primarily speak and understand only the test language, is one important step in the translation process. Reproductive health questionnaires were tested with persons monolingual in Hindi, Tamil, Urdu, Spanish, and French. Testing revealed problematic questions and how culture, education, and migration experience can affect perceptions of questions. Bilingual liaisons from the communities of interest facilitated recruitment of participants, but liaisons' vulnerable status and lack of familiarity with research posed challenges to the testing process. When conducting monolingual testing it is important to: carefully select liaisons (consider their gender, host-language fluency, knowledge of research processes, and comfort with the subject matter of the research); recruit monolingual persons with characteristics representative of the research population; ensure adequate researcher involvement in all aspects of the testing process to triangulate data collection from various sources. PMID- 20572096 TI - A CVS start-up. PMID- 20572097 TI - What can we expect from invasive procedures in 10 years time? PMID- 20572098 TI - By 2020... PMID- 20572095 TI - Quality nursing care for hospitalized patients with advanced illness: concept development. AB - The quality of nursing care as perceived by hospitalized patients with advanced illness has not been examined. A concept of quality nursing care for this population was developed by integrating the literature on constructs defining quality nursing care with empirical findings from interviews of 16 patients with advanced illness. Quality nursing care was characterized as competence and personal caring supported by professionalism and delivered with an appropriate demeanor. Although the attributes of competence, caring, professionalism, and demeanor were identified as common components of quality care across various patient populations, the caring domain increased in importance when patients with advanced illness perceived themselves as vulnerable. Assessment of quality nursing care for patients with advanced illness needs to include measures of patient perceptions of vulnerability. PMID- 20572099 TI - Cytogenetics in the 1970s and 1980s. PMID- 20572100 TI - Molecular diagnosis of hemoglobinopathies and thalassemia. PMID- 20572101 TI - Early sonographic prenatal diagnosis. PMID- 20572102 TI - From Michael to microarrays: 30 years of studying fetal cells and nucleic acids in maternal blood. PMID- 20572103 TI - Noninvasive prenatal diagnosis in 2020. PMID- 20572104 TI - Prenatal screening for open neural tube defects and Down syndrome: three decades of progress. PMID- 20572105 TI - Fetal therapy: 2020 and beyond. PMID- 20572106 TI - The history of the second-trimester sonographic markers for detecting fetal Down syndrome, and their current role in obstetric practice. AB - This review summarizes the development, history and use of second-trimester sonographic markers for the detection of fetal Down syndrome over three decades. Starting with the nuchal fold thickening in 1985 and culminating in the genetic sonogram in the 1990 s. The combination of second-trimester serum screening with the ultrasound markers improved the detection rate of affected fetuses but also allowed patients to decrease their risk of carrying a fetus with Down syndrome if the genetic sonogram was normal. More recently the role of the genetic sonogram and its markers have changed with the wide spread use of first-trimester screening. This prior screening ultimately decreases the prevalence of fetal Down syndrome in the second trimester to less than 85% of what it was in the first trimester as most fetuses with Down syndrome are now identified early. Current interpretation of the second-trimester Down syndrome markers must be based on the result of the first trimester and combined screening to achieve the most accurate risk estimate of an affected fetus. PMID- 20572107 TI - Fetal cardiac scanning today. AB - The ability to examine the structure of the fetal heart in real-time started over 30 years ago now. The field has seen very great advances since then, both in terms of technical improvements in ultrasound equipment and in dissemination of operator skills. A great deal has been learnt about normal cardiac function in the human fetus throughout gestation and how it is affected by pathologies of pregnancy. There is increasing recognition of abnormal heart structure during routine obstetric scanning, allowing referral for specialist diagnosis and counselling. It is now possible to make accurate diagnosis of cardiac malformations as early as 12 weeks of gestation. Early diagnosis of a major cardiac malformation in the fetus can provide the parents with a comprehensive prognosis, enabling them to make the most informed choice about the management of the pregnancy. PMID- 20572108 TI - Early fetal therapy. PMID- 20572109 TI - The future of prenatal cytogenetic diagnostics: a personal perspective. PMID- 20572110 TI - Management of red cell alloimmunisation in pregnancy: the non-invasive monitoring of the disease. AB - Haemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization was a significant cause of fetal and neonatal morbidity and mortality until the introduction of anti-D immunoglobulin, which has dramatically changed the incidence of the disease. However, it is still a major problem in affected pregnancies. The emphasis of current clinical management has shifted from an invasive approach to non-invasive monitoring of the disease. The key elements of the modern management are determining which fetuses are at risk of HDFN with the use of cell-free fetal DNA in maternal plasma (fetal RHD genotype) and the follow-up of antigen positive fetuses by Doppler ultrasonography to detect anaemia severe enough to need treatment. When anaemia is suspected, an invasive approach is still required in a timely manner for confirmation of the degree of anaemia and to administer blood transfusions. This non-invasive approach prevents unnecessary administration of human-derived blood products, with the consequent ethical and cost implications and most importantly avoids iatrogenic conversion of mild to severe disease by avoiding need for techniques such as amniocentesis. The potential problem of the non-invasive approach is the reduction in the total number of invasive procedures, with the subsequent difficulty of maintaining the skills required to perform them. PMID- 20572111 TI - Preimplantation genetic diagnosis at 20 years. AB - First reported in 1990, PGD has evolved into a complementary form of prenatal diagnosis offering novel indications. DNA for PGD can be recovered with equal safety and facility from polar bodies I and II, blastomere (8 cell embryo) and trophectoderm (5-6 day blastocyst). Diagnostic accuracy is very high (>99%) for both chromosomal abnormalities and single gene disorders. Traditional application of FISH with chromosome specific probes for detecting aneuploidy and translocations may be replaced or complemented by array comparative genome hybridization (array CGH); biopsied embryos can now be cryopreserved (vitrification) while analysis proceeds in orderly fashion. PGD has been accomplished for over 200 different single gene disorders. Novel indications for PGD not readily applicable by traditional prenatal genetic diagnosis include avoiding clinical pregnancy termination, performing preconceptional diagnosis (polar body I), obtaining prenatal diagnosis without disclosure of prenatal genotype (nondisclosure), diagnosing adult-onset disorders particularly cancer, and identifying HLA compatible embryos suitable for recovering umbilical cord blood stem cells. PMID- 20572112 TI - Three-dimensional ultrasound in evaluating the fetus. AB - In recent years three-dimensional (3D) ultrasound has made a place in clinical practice and has become a major field of research in obstetrics. In this article we will review the diagnostic performance of the most widely used 3D ultrasound applications in the assessment of fetal anomalies, explain the technique to gain correct 3D images and offer some practical advice for their efficient use. Examples are given to demonstrate the applicability and vividness of 3D in daily routine. PMID- 20572113 TI - Fetal ultrasound screening and diagnosis 10 years hence. PMID- 20572114 TI - The making of fetal surgery. AB - Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990 s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials. PMID- 20572115 TI - The evolution of prenatal diagnosis. PMID- 20572116 TI - Prenatal Diagnosis: past, present, and future. PMID- 20572117 TI - Molecular prenatal diagnosis: the impact of modern technologies. AB - Originally prenatal diagnosis was confined to the diagnosis of metabolic disorders and depended on assaying enzyme levels in amniotic fluid. With the development of recombinant DNA technology, molecular diagnosis became possible for some genetic conditions late in the 1970s. Here we briefly review the history of molecular prenatal diagnostic testing, using Duchenne muscular dystrophy as an example, and describe how over the last 30 years we have moved from offering testing to a few affected individuals using techniques, such as Southern blotting to identify deletions, to more rapid and accurate PCR-based testing which identifies the precise change in dystrophin for a greater number of families. We discuss the potential for safer, earlier prenatal genetic diagnosis using cell free fetal DNA in maternal blood before concluding by speculating on how more recent techniques, such as next generation sequencing, might further impact on the potential for molecular prenatal testing. Progress is not without its challenges, and as cytogenetics and molecular genetics begin to unite into one, we foresee the main challenge will not be in identifying the genetic change, but rather in interpreting its significance, particularly in the prenatal setting where we frequently have no phenotype on which to base interpretation. PMID- 20572118 TI - The 18-week fetal examination and detection of anomalies. AB - From its beginning in the fifties the use of ultrasound in gynaecology and obstetrics has expanded extensively. Ultrasound technology has taken us from a time when the mother was our prime focus to the present where it is the unborn baby. Ultrasound assessments may have significant consequences for pregnancy care by optimizing the time, the mode and the location of the delivery as well as preparing the postnatal staff for a prenatally defined fetal problem. A major factor in the development was the groundbreaking work of an obstetrician, Ian Donald, and an engineer, Tom Brown, at Queen Mother's Hospital in Glasgow, who produced an ultrasound instrument called the Diasonograph. The first screening program offering a systematic ultrasound examination to a large pregnant population began in Malmoe, in 1973 and aimed to detect twins. Since then the examination has evolved over the years to include a systematic evaluation of the intrauterine contents. A number of randomized controlled trials have been reported and several large studies have reported the efficiency of routine fetal examinations for the detection of anomalies. Detection rates for the various subsets are presented. The learning curve regarding the ability to detect anomalies and the importance of proper training has also been shown. The procedure 'routine fetal examination' has been significant in supporting the continuous development of fetal medicine. The consequences of the improved dating of every pregnancy and the in utero transport of a sick fetus rather than an emergency transportation of a sick neonate, have an established evidence base. Ultrasound technology has had a remarkable ability to trigger great technical minds to move the technology forward year after year. Through a continuous cooperation between technicians and clinicians, this impressive technology of ultrasound will continue to support our work for the unborn child. PMID- 20572119 TI - A Bayesian model averaging approach with non-informative priors for cost effectiveness analyses. AB - We consider the problem of assessing new and existing technologies for their cost effectiveness in the case where data on both costs and effects are available from a clinical trial, and we address it by means of the cost-effectiveness acceptability curve. The main difficulty in these analyses is that cost data usually exhibit highly skew and heavy-tailed distributions, so that it can be extremely difficult to produce realistic probabilistic models for the underlying population distribution. Here, in order to integrate the uncertainty about the model into the analysis of cost data and into cost-effectiveness analyses, we consider an approach based on Bayesian model averaging (BMA) in the particular case of weak prior informations about the unknown parameters of the different models involved in the procedure. The main consequence of this assumption is that the marginal densities required by BMA are undetermined. However, in accordance with the theory of partial Bayes factors and in particular of fractional Bayes factors, we suggest replacing each marginal density with a ratio of integrals that can be efficiently computed via path sampling. PMID- 20572120 TI - Estimating treated prevalence and service utilization rates: assessing disparities in mental health. AB - There is considerable public concern about health disparities among different cultural/racial/ethnic groups. Important process measures that might reflect inequities are treated prevalence and the service utilization rate in a defined period of time. We have previously described a method for estimating N, the distinct number who received service in a year, from a survey of service users at a single point in time. The estimator is based on the random variable 'time since last service', which enables the estimation of treated prevalence. We show that this same data can be used to estimate the service utilization rate, E(J), the mean number of services in the year. If the sample is typical with respect to the time since last visit, the MLE of E(J) is asymptotically unbiased. Confidence intervals and a global test of equality of treated prevalence and service utilization rates among several groups are given. A data set of outpatient mental health services from a county in New York State for which the true values of the parameters are known is analyzed as an illustration of the methods and an appraisal of their accuracy. PMID- 20572122 TI - A flexible unified approach to the analysis of pre-clinical combination studies. AB - Combinations of drugs are increasingly being used in a variety of diseases. Pre clinical experiments allow the responses of many drug compounds to be studied in combination with the goal of identifying compounds acting synergistically. This paper presents a unified approach to analysing data from combination studies, calculating a hierarchy of interaction indices to powerfully and flexibly describe the synergistic profile of the combination space studied, utilizing standard statistical software to generate estimates of confidence and provide statistical tests. The approach can work with a wide variety of experimental designs and response patterns and will deal with partial responses and inactive compounds. As well as identifying synergy or antagonism, the same approach can also be used to identify a benefit or detriment to monotherapy. The approach is illustrated with data from an in vitro study. PMID- 20572121 TI - Likelihood-based methods for estimating the association between a health outcome and left- or interval-censored longitudinal exposure data. AB - The Michigan Female Health Study (MFHS) conducted research focusing on reproductive health outcomes among women exposed to polybrominated biphenyls (PBBs). In the work presented here, the available longitudinal serum PBB exposure measurements are used to obtain predictions of PBB exposure for specific time points of interest via random effects models. In a two-stage approach, a prediction of the PBB exposure is obtained and then used in a second-stage health outcome model. This paper illustrates how a unified approach, which links the exposure and outcome in a joint model, provides an efficient adjustment for covariate measurement error. We compare the use of empirical Bayes predictions in the two-stage approach with results from a joint modeling approach, with and without an adjustment for left- and interval-censored data. The unified approach with the adjustment for left- and interval-censored data resulted in little bias and near-nominal confidence interval coverage in both the logistic and linear model setting. PMID- 20572123 TI - Joint modeling of progression-free survival and death in advanced cancer clinical trials. AB - Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer. PMID- 20572124 TI - Combining stratified and unstratified log-rank tests in paired survival data. AB - The log-rank test is the most widely used nonparametric method for testing treatment differences in survival between two treatment groups due to its efficiency under the proportional hazards model. Most previous work on the log rank test has assumed that the samples from the two treatment groups are independent. This assumption is not always true. In multi-center clinical trials, survival times of patients in the same medical center may be correlated due to factors specific to each center. For such data, we can construct both stratified and unstratified log-rank tests. These two tests turn out to have very different powers for correlated samples. An appropriate linear combination of these two tests may give a more powerful test than either of the individual test. Under a bivariate frailty model, we obtain closed-form asymptotic local alternative distributions and the correlation coefficient between these two tests. Based on these results we construct an optimal linear combination of the two test statistics to maximize the local power. Simulation studies with Hougaard's model confirm our construction. We also study the robustness of the combined test by simulations. PMID- 20572125 TI - Effects of calcium supplements on fracture healing in a rat osteoporotic model. AB - Fracture healing is a complex process, which is further complicated if the bone is osteoporotic. Calcium is one of the important minerals in bone and has been found to prevent osteoporosis but its role in fracture healing of osteoporotic bone is still unclear. We carried out a study on the effects of calcium supplementation on the late phase healing of fractured osteoporotic bone using an ovariectomized rat model. Twenty-four female Sprague-Dawley rats were divided into three groups: sham-operated (SO), ovariectomized-control (OVXC), and ovariectomized + calcium supplements (Ca). The right femurs of all the rats were fractured at mid-epiphysis and a K-wire was inserted for internal fixation. After 2 months of treatment, the rats were sacrificed and the femora were dissected out for radiological and biomechanical assessment. As expected, osteoporosis resulted in impaired healing as shown by the poor radiological and biomechanical properties of the OVXC group. CT scans showed significantly lower callus volumes in the SO and Ca groups compared to the OVXC group. Radiological scoring of fracture healing and callus staging of the SO and Ca groups were better than the OVXC group. However, the biomechanical parameters of the Ca group were significantly lower than the SO group and similar to the OVXC group. Therefore, calcium supplements may appear to improve fracture healing of osteoporotic bone but failed to improve strength. PMID- 20572126 TI - Production and characterization of a recombinant beta-1,4-endoglucanase (glycohydrolase family 9) from the termite Reticulitermes flavipes. AB - Cell-1 is a host-derived beta-1,4-endoglucanase (Glycohydrolase Family 9 [GHF9]) from the lower termite Reticulitermes flavipes. Here, we report on the heterologous production of Cell-1 using eukaryotic (Baculovirus Expression Vector System; BEVS) and prokaryotic (E. coli) expression systems. The BEVS-expressed enzyme was more readily obtained in solubilized form and more active than the E. coli-expressed enzyme. K(m) and V(max) values for BEVS-expressed Cell-1 against the model substrate CMC were 0.993% w/v and 1.056 micromol/min/mg. Additional characterization studies on the BEVS-expressed enzyme revealed that it possesses activity comparable to the native enzyme, is optimally active around pH 6.5-7.5 and 50-60 degrees C, is inhibited by EDTA, and displays enhanced activity up to 70 degrees C in the presence of CaCl(2). These findings provide a foundation on which to begin subsequent investigations of collaborative digestion by coevolved host and symbiont digestive enzymes from R. flavipes that include GHF7 exoglucanases, GHF1 beta glucosidases, phenol-oxidizing laccases, and others. PMID- 20572127 TI - Analysis of expressed sequence tags from a significant livestock pest, the stable fly (Stomoxys calcitrans), identifies transcripts with a putative role in chemosensation and sex determination. AB - The stable fly, Stomoxys calcitrans L. (Diptera: Muscidae), is one of the most significant pests of livestock in the United States. The identification of targets for the development of novel control for this pest species, focusing on those molecules that play a role in successful feeding and reproduction, is critical to mitigating its impact on confined and rangeland livestock. A database was developed representing genes expressed at the immature and adult life stages of the stable fly, comprising data obtained from pyrosequencing both immature and adult stages and from small-scale sequencing of an antennal/maxillary palp expressed sequence tag library. The full-length sequence and expression of 21 transcripts that may have a role in chemosensation is presented, including 13 odorant-binding proteins, 6 chemosensory proteins, and 2 odorant receptors. Transcripts with potential roles in sex determination and reproductive behaviors are identified, including evidence for the sex-specific expression of stable fly doublesex- and transformer-like transcripts. The current database will be a valuable tool for target identification and for comparative studies with other Diptera. PMID- 20572128 TI - Imaging iron-loaded mouse glioma tumors with bSSFP at 3 T. AB - The poor prognosis for patients with high-grade glioma is partly due to the invasion of tumor cells into surrounding brain tissue. The goal of the present work was to develop a mouse model of glioma that included the potential to track cell invasion using MRI by labeling GL261 cells with iron oxide contrast agents prior to intracranial injection. Two types of agents were compared with several labeling schemes to balance between labeling with sufficient iron to curb the dilution effect of cell division while avoiding overwhelming signal loss that could prevent adequate visualization of tumor boundaries. The balanced steady state free precession (bSSFP) pulse sequence was evaluated for its suitability for imaging glioma tumors and compared to T(2)-weighted two-dimensional fast spin echo (FSE) and T(1)-weighted spoiled gradient recalled echo (SPGR) at 3 T in terms of signal-to-noise ratio and contrast-to-noise ratio efficiencies. Ultimately, a three-dimensional bSSFP protocol consisting of a set of two images with complementary contrasts was developed, allowing excellent tumor visualization with minimal iron contrast when using pulse repetition time = 6 ms and alpha = 40 degrees, and extremely high sensitivity to iron when using pulse repetition time = 22 ms and alpha = 20 degrees. Quantitative histologic analysis validated that the strong signal loss seen in balanced steady state free precession pulse sequence images of iron-loaded tumors correlated well with the presence of iron. PMID- 20572130 TI - Nonbalanced SSFP-based quantitative magnetization transfer imaging. AB - The previously reported concept for quantitative magnetization transfer (MT) imaging using balanced steady-state free precession (SSFP) is applied to nonbalanced SSFP sequences. This offers the possibility to derive quantitative MT parameters of targets with high-susceptibility variations such as the musculoskeletal system, where balanced SSFP suffers from off-resonance-related signal loss. In the first part of this work, an extended SSFP free induction decay (SSFP-FID) signal equation is derived based on a binary spin-bath model. Based on this new description, quantitative MT parameters such as the fractional pool size, magnetization exchange rate, and relaxation times can be assessed. In the second part of this work, MT model parameters are derived from an ex vivo muscle sample, in vivo human femoral muscle, and in vivo human patellar cartilage. Motion sensitivity issues are discussed and results from two-pool SSFP FID are compared to results from two-pool balanced SSFP and common quantitative MT models. In summary, this work demonstrates that SSFP-FID allows for quantitative MT imaging of targets with high-susceptibility variations within short acquisition times. PMID- 20572129 TI - Tensor kernels for simultaneous fiber model estimation and tractography. AB - This paper proposes a novel framework for joint orientation distribution function estimation and tractography based on a new class of tensor kernels. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. In this work, fiber tracking is formulated as recursive estimation: at each step of tracing the fiber, the current estimate of the orientation distribution function is guided by the previous. To do this, second and higher-order tensor-based kernels are employed. A weighted mixture of these tensor kernels is used for representing crossing and branching fiber structures. While tracing a fiber, the parameters of the mixture model are estimated based on the orientation distribution function at that location and a smoothness term that penalizes deviation from the previous estimate along the fiber direction. This ensures smooth estimation along the direction of propagation of the fiber. In synthetic experiments, using a mixture of two and three components it is shown that this approach improves the angular resolution at crossings. In vivo experiments using two and three components examine the corpus callosum and corticospinal tract and confirm the ability to trace through regions known to contain such crossing and branching. PMID- 20572131 TI - Multiplex RARE: a simultaneous multislice spin-echo sequence that fulfils CPMG conditions. AB - This work presents a new imaging sequence in which multiple slices are simultaneously excited and refocused in a spin-echo train. The multiple spin-echo trains are interleaved in such a manner that (i) the Carr-Purcell-Meiboom-Gill conditions are fulfilled at all times, and (ii) the signals from slices can be separated, preventing aliasing. This paper also demonstrates how the sequence may be used in a novel fat-water Dixon method that enables fast volume coverage. The technique is demonstrated in phantoms and in vivo. PMID- 20572132 TI - Gadolinium-labeled quantum dots for molecular magnetic resonance imaging: R1 versus R2 mapping. AB - Quantum dots labeled with paramagnetic gadolinium chelates can be applied as contrast agent for preclinical molecular MRI combined with fluorescence microscopy. Besides increasing the longitudinal relaxation rate, gadolinium labeled quantum dots may increase the transverse relaxation rate, which might be related to their magnetic properties. Furthermore, molecular MRI experiments are primarily conducted at high magnetic fields, where longitudinal relaxation rate becomes less effective, and the use of transverse relaxation rate as a source of contrast may become attractive. Consequently, the optimal method of contrast enhancement using gadolinium-labeled quantum dots is a priori unknown. The objective of this study was to compare longitudinal relaxation rate- and transverse relaxation rate-based contrast enhancement, proton visibility, and changes thereof induced by gadolinium-labeled quantum dots targeted to the angiogenic vasculature of murine tumors, using in vivo longitudinal and transverse relaxation rate mapping. At a field strength of 7 T, longitudinal relaxation rate-based measures were superior to transverse relaxation rate-based measures in detecting both the level and spatial extent of contrast agent-induced relaxation rate changes. PMID- 20572133 TI - In vivo MRI measurement of fetal blood oxygen saturation in cardiac ventricles of fetal sheep: a feasibility study. AB - The purpose of this study was to assess the feasibility to determine fetal blood oxygen saturation (sO(2)) with T(2)-weighted MR sequences using a fetal sheep model. T(2) measurements were performed on a 1.5-T scanner using a T(2) preparation pulse in combination with a three-dimensional balanced steady-state free precession sequence repeated at different echo times. Eight sheep fetuses were examined during a control, hypoxic, and recovery phase to perform T(2) weighted scans of the fetal blood in the heart. Signal intensities in the left and right ventricle were measured to calculate the MR blood sO(2). During each phase, fetal carotid artery sO(2) was directly measured and correlated with MR sO(2). A Bland-Altman plot was performed. Fetal carotid artery sO(2) was 69% sO(2) during control, 16% sO(2) during hypoxemia, and 67% sO(2) during recovery. Mean values of the MR sO(2) were 49% sO(2) and 40% sO(2) for control, 6% sO(2) and 3% sO(2) for hypoxemia, and 51% sO(2) and 43% sO(2) for recovery in left ventricle and right ventricle, respectively. Mean values of fetal carotid artery sO(2) and MR sO(2) were highly correlated (left ventricle: r = 0.87, right ventricle: r = 0.89). According to the Bland-Altman plot, MR sO(2) was lower compared to fetal carotid artery sO(2) (left ventricle: 15%, right ventricle: 20%). Based on our preliminary results, it seems to be possible to assess fetal sO(2) with MR oximetry. PMID- 20572134 TI - Data convolution and combination operation (COCOA) for motion ghost artifacts reduction. AB - A novel method, data convolution and combination operation, is introduced for the reduction of ghost artifacts due to motion or flow during data acquisition. Since neighboring k-space data points from different coil elements have strong correlations, a new "synthetic" k-space with dispersed motion artifacts can be generated through convolution for each coil. The corresponding convolution kernel can be self-calibrated using the acquired k-space data. The synthetic and the acquired data sets can be checked for consistency to identify k-space areas that are motion corrupted. Subsequently, these two data sets can be combined appropriately to produce a k-space data set showing a reduced level of motion induced error. If the acquired k-space contains isolated error, the error can be completely eliminated through data convolution and combination operation. If the acquired k-space data contain widespread errors, the application of the convolution also significantly reduces the overall error. Results with simulated and in vivo data demonstrate that this self-calibrated method robustly reduces ghost artifacts due to swallowing, breathing, or blood flow, with a minimum impact on the image signal-to-noise ratio. PMID- 20572135 TI - Contrast agent influences MRI phase-contrast flow measurements in small vessels. AB - Contrast-enhanced MR angiography is often combined with phase contrast (PC) flow measurement to answer a particular clinical question. The contrast agent that is administered during contrast-enhanced MR angiography may still be present in the blood during the consecutive PC flow measurement. The aim of this work was to evaluate the influence of contrast agent on PC flow measurements in small vessels. For that purpose, both in vivo measurements and computer simulations were performed. The dependence of the PC flow quantification on the signal amplitude difference between blood and stationary background tissue for various vessel sizes was characterized. Results show that the partial-volume effect strongly affects the accuracy of the PC flow quantification when the imaged vessel is small compared to the spatial resolution. A higher blood-to-background contrast level during imaging significantly increases the partial-volume effect and thereby reduces the accuracy of the flow quantification. On the other hand, a higher blood-to-background-contrast level facilitated the segmentation of the vessel for flow rate determination. PC flow measurements should therefore be performed after contrast agent administration in large vessels, but before contrast agent administration in small vessels. PMID- 20572136 TI - Accelerated 3D catheter visualization from triplanar MR projection images. AB - One major obstacle for MR-guided catheterizations is long acquisition times associated with visualizing interventional devices. Therefore, most techniques presented hitherto rely on single-plane imaging to visualize the catheter. Recently, accelerated three-dimensional (3D) imaging based on compressed sensing has been proposed to reduce acquisition times. However, frame rates with this technique remain low, and the 3D reconstruction problem yields a considerable computational load. In X-ray angiography, it is well understood that the shape of interventional devices can be derived in 3D space from a limited number of projection images. In this work, this fact is exploited to develop a method for 3D visualization of active catheters from multiplanar two-dimensional (2D) projection MR images. This is favorable to 3D MRI as the overall number of acquired profiles, and consequently the acquisition time, is reduced. To further reduce measurement times, compressed sensing is employed. Furthermore, a novel single-channel catheter design is presented that combines a solenoidal tip coil in series with a single-loop antenna, enabling simultaneous tip tracking and shape visualization. The tracked tip and catheter properties provide constraints for compressed sensing reconstruction and subsequent 2D/3D curve fitting. The feasibility of the method is demonstrated in phantoms and in an in vivo pig experiment. PMID- 20572137 TI - Deep venous thrombosis: diagnostic value of non-contrast-enhanced MR venography using electrocardiography-triggered three-dimensional half-Fourier FSE. AB - We prospectively assessed the diagnostic accuracy of non-contrast-enhanced MR venography using both the flow-refocused fresh-blood imaging (FR-FBI) and the swap phase-encode arterial double-subtraction elimination (SPADE) techniques for detecting deep vein thrombosis (DVT), as compared using conventional X-ray venography as the reference standard. Forty-one legs of 32 consecutive patients (eight men, 24 women; mean age +/- standard deviation, 69.4 +/- 15.3 years) suspected of having deep vein thrombosis and thus examined using conventional X ray venography underwent MR FR-FBI and SPADE. Twenty-five of the 32 patients had nonmagnetizing, metal implants they had received during hip or leg surgery. Two radiologists independently assessed the MR venograms as either diagnostic or nondiagnostic and with either the presence or absence of thrombi. The sensitivities of FR-FBI and SPADE for diagnosing thrombus were 100% (53 of 53) for both reviewers. Nondiagnostic segments were excluded from this analysis. The corresponding specificities were 100% (238 of 238 for reviewer A) and 99.6% (237 of 238 for reviewer B). The interobserver agreement regarding the MR images for the assessment of thrombosis was high (kappa = 0.92). Non-contrast-enhanced MR venography using SPADE and FR-FBI is highly accurate and reproducible for diagnosing DVT. This is especially advantageous for patients who have received nonmagnetizing, metal implants during orthopedic surgery. PMID- 20572138 TI - Multishot PROPELLER for high-field preclinical MRI. AB - With the development of numerous mouse models of cancer, there is a tremendous need for an appropriate imaging technique to study the disease evolution. High field T(2)-weighted imaging using PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI meets this need. The two-shot PROPELLER technique presented here provides (a) high spatial resolution, (b) high contrast resolution, and (c) rapid and noninvasive imaging, which enables high throughput, longitudinal studies in free-breathing mice. Unique data collection and reconstruction makes this method robust against motion artifacts. The two shot modification introduced here retains more high-frequency information and provides higher signal-to-noise ratio than conventional single-shot PROPELLER, making this sequence feasible at high fields, where signal loss is rapid. Results are shown in a liver metastases model to demonstrate the utility of this technique in one of the more challenging regions of the mouse, which is the abdomen. PMID- 20572139 TI - Modeling the influence of TR and excitation flip angle on the magnetization transfer ratio (MTR) in human brain obtained from 3D spoiled gradient echo MRI. AB - Attempts to optimize the magnetization transfer ratio (MTR) obtained from spoiled gradient echo MRI have focused on the properties of the magnetization transfer pulse. In particular, continuous-wave models do not explicitly account for the effects of excitation and relaxation on the MTR. In this work, these were modeled by an approximation of free relaxation between the radiofrequency pulses and of an instantaneous saturation event describing the magnetization transfer pulse. An algebraic approximation of the signal equation can be obtained for short pulse repetition time and small flip angles. This greatly facilitated the mathematical treatment and understanding of the MTR. The influence of inhomogeneous radiofrequency fields could be readily incorporated. The model was verified on the human brain in vivo at 3 T by variation of flip angle and pulse repetition time. The corresponding range in MTR was similar to that observed by a 4-fold increase of magnetization transfer pulse power. Choice of short pulse repetition time and larger flip angles improved the MTR contrast and reduced the influence of radiofrequency inhomogeneity. Optimal contrast is obtained around an MTR of 50%, and noise progression is reduced when a high reference signal is obtained. PMID- 20572140 TI - A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle. AB - MR techniques have proven their ability to investigate skeletal muscle function in situ. Their benefit in terms of noninvasiveness is, however, lost in animal research, given that muscle stimulation and force output measurements are usually achieved using invasive surgical procedures, thereby excluding repeated investigations in the same animal. This study describes a new setup allowing strictly noninvasive investigations of mouse gastrocnemius muscle function using (1)H-MRI and (31)P-MR spectroscopy. Its originality is to integrate noninvasive systems for inducing muscle contraction through transcutaneous stimulation and for measuring mechanical performance with a dedicated ergometer. In order to test the setup, muscle function was investigated using a fatiguing stimulation protocol (6 min of repeated isometric contractions at 1.7 Hz). T(2)-weighted imaging demonstrated that transcutaneous stimulation mainly activated the gastrocnemius. Moreover, investigations repeated twice with a 7-day interval between bouts did show a high reproducibility in measurements with regard to changes in isometric force and energy metabolism. In conclusion, this setup enables us for the first time to access mechanical performance, energy metabolism, anatomy, and physiology strictly noninvasively in contracting mouse skeletal muscle. The possibility for implementing longitudinal studies opens up new perspectives in many research areas, including ageing, pharmaceutical research, and gene and cell therapy. PMID- 20572141 TI - Bone vascularization and trabecular bone formation are mediated by PKB alpha/Akt1 in a gene-dosage-dependent manner: in vivo and ex vivo MRI. AB - PKBalpha/Akt1, a protein kinase, is a major mediator of angiogenic signaling. The purpose of this study was to determine the role of PKB alpha/Akt1 in bone vascularization and development. For that aim, macromolecular dynamic contrast enhanced MRI was applied to examine in vivo vascular changes in long bones of 40 day-old growing PKB alpha/Akt1-deficient, heterozygous, and wild-type mice. Ex vivo microMRI and microCT were applied to monitor the impact of PKB alpha/Akt1 gene dosage on trabecular bone formation during endochondral bone growth. PKB alpha/Akt1-deficient mice and, remarkably, also heterozygous mice showed significantly reduced blood volume fraction in the humerus compared to wild-type mice. Moreover, PKB alpha/Akt1-deficient mice showed a more severe vascular deficiency with reduced permeability. microCT and microMRI of trabeculae revealed impaired bone formation in both PKB alpha/Akt1-deficient and heterozygous mice, whereas cortical bone parameters were only reduced in PKB alpha/Akt1-deficient mice. Reduction of metaphyseal blood vessel invasion, concomitant with aberrant trabeculae and shorter long bones, demonstrates a gene-dose-dependent role for PKB alpha/Akt1 in regulation of overall size and endochondral bone growth. MRI proved to provide high sensitivity for in vivo detection of subtle gene dose effects leading to impaired bone vascularity and for uncovering changes in trabecular bone. PMID- 20572142 TI - 2D and 3D radial multi-gradient-echo DCE MRI in murine tumor models with dynamic R*2-corrected R1 mapping. AB - Dynamic contrast-enhanced MRI is extensively studied to define and evaluate biomarkers for early assessment of vasculature-targeting therapies. In this study, two-dimensional and three-dimensional radial multi-gradient-echo techniques for dynamic R*(2)-corrected R(1) mapping based on the spoiled gradient recalled signal equation were implemented and validated at 4.7 T. The techniques were evaluated on phantoms and on a respiratory motion animated tumor model. R(1) measurements were validated with respect to a standard inversion-recovery spin echo sequence in a four-compartment phantom covering a range of relaxation rates typically found in tumor tissue. In the range of [0.4, 3] sec(-1), R(1) differences were less than 10% for both two-dimensional and three-dimensional experiments. A dynamic contrast-enhanced MRI pilot study was performed on a colorectal tumor model subcutaneously implanted in mice at the abdominal level. Low motion sensitivity of radial acquisition allowed image recording without respiratory triggering. Three-dimensional K(trans) maps and significantly different mean K(trans) values were obtained for two contrast agents with different molecular weights. The radial multi-gradient-echo approach should be most useful for preclinical experimental conditions where the tissue of interest experiences physiologic motion, like spontaneous extracerebral tumors developed by transgenic mice, and where dynamic contrast-enhanced MRI is performed with high-relaxivity contrast agents. PMID- 20572143 TI - High-resolution magnetization-prepared 3D-FLAIR imaging at 7.0 Tesla. AB - The aim of the present study is to develop a submillimeter volumetric (three dimensional) fluid-attenuated inversion recovery sequence at 7T. Implementation of the fluid-attenuated inversion recovery sequence is difficult as increased T(1) weighting from prolonged T(1) constants at 7T dominate the desired T(2) contrast and yield suboptimal signal-to-noise ratio. Magnetization preparation was used to reduce T(1) weighting and improve the T(2) weighting. Also, practical challenges limit the implementation. Long refocusing trains with low flip angles were used to mitigate the specific absorption rate constraints. This resulted in a three-dimensional magnetization preparation fluid-attenuated inversion recovery sequence with 0.8 x 0.8 x 0.8 = 0.5 mm(3) resolution in a clinically acceptable scan time. The contrast-to-noise ratio between gray matter and white matter (contrast-to-noise ratio = signal-to-noise ratio [gray matter] - signal-to-noise ratio [white matter]) increased from 12 +/- 9 without magnetization preparation to 28 +/- 8 with magnetization preparation (n = 12). The signal-to-noise ratio increased for white matter by 13 +/- 6% and for gray matter by 48 +/- 15%. In conclusion, three-dimensional fluid-attenuated inversion recovery with high resolution and full brain coverage is feasible at 7T. Magnetization preparation reduces the T(1) weighting, thereby improving the T(2) weighted contrast and signal-to-noise ratio. PMID- 20572144 TI - Real-time adaptive sequential design for optimal acquisition of arterial spin labeling MRI data. AB - An optimal sampling schedule strategy based on the Fisher information matrix and the D-optimality criterion has previously been proposed as a formal framework for optimizing inversion time scheduling for multi-inversion-time arterial spin labeling experiments. Optimal sampling schedule possesses the primary advantage of improving parameter estimation precision but requires a priori estimation of plausible parameter distributions that may not be available in all situations. An adaptive sequential design approach addresses this issue by incorporating the optimal sampling schedule strategy into an adaptive process that iteratively updates the parameter estimates and adjusts the optimal sampling schedule accordingly as data are acquired. In this study, the adaptive sequential design method was experimentally implemented with a real-time feedback scheme on a clinical MRI scanner and was tested in six normal volunteers. Adapted schedules were found to accommodate the intrinsically prolonged arterial transit times in the occipital lobe of the brain. Simulation of applying the adaptive sequential design approach on subjects with pathologically reduced perfusion was also implemented. Simulation results show that the adaptive sequential design approach is capable of incorporating pathologic parameter information into an optimal arterial spin labeling scheduling design within a clinically useful experimental time. PMID- 20572146 TI - Real-time single-heartbeat fast strain-encoded imaging of right ventricular regional function: normal versus chronic pulmonary hypertension. AB - Patients with pulmonary hypertension and suspected right ventricular (RV) dysfunction often have dyspnea at rest, making reliable assessment of RV function using traditional breath-holding methods difficult to perform. Using single heartbeat fast strain encoding (Fast-SENC) imaging, peak systolic RV circumferential and longitudinal strains were measured in 11 healthy volunteers and 11 pulmonary hypertension patients. Fast-SENC RV longitudinal strain and circumferential strain measurements were compared to conventional SENC and MR tagging, respectively. Fast-SENC circumferential and longitudinal RV shortening correlated closely with SENC measurements (r = 0.86, r = 0.90, P < 0.001 for all). Circumferential strain, by conventional tagging, showed moderate correlation with Fast-SENC in pulmonary hypertension patients only (r = 0.5, P = 0.003). A nonuniform pattern of RV circumferential shortening was depicted in both groups. Peak systolic circumferential strain was significantly reduced at the basal RV in pulmonary hypertension patients (-18.06 +/- 3.3 versus -21.9 +/- 1.9, P < 0.01) compared to normal individuals, while peak systolic longitudinal strain was significantly reduced at all levels (P < 0.01 for all). Fast-SENC is a feasible and reliable technique for rapid quantification of RV regional function in a single-heartbeat acquisition. Information derived from Fast-SENC allows characterization of RV regional function in normal individuals and in pulmonary hypertension patients. PMID- 20572145 TI - S-Gal, a novel 1H MRI reporter for beta-galactosidase. AB - Reporter genes and associated enzyme activity are becoming increasingly significant for research in vivo. The lacZ gene and beta-galactosidase (beta-gal) expression have long been exploited as reporters of biologic manipulation at the molecular level, and a noninvasive detection strategy based on proton MRI is particularly attractive. 3,4-Cyclohexenoesculetin beta-D-galactopyranoside (S Gal) is a commercial histologic stain, which forms a black precipitate in the presence of beta-gal and ferric ions, suggesting potential detectability by MRI. Generation of the precipitate is now shown to cause strong T(2)* relaxation, revealing beta-gal activity. A series of tests with the enzyme in vitro and with tumor cells shows that this approach can be used as an assay for beta-gal activity. Proof of principle is shown in human breast tumor xenografts in mice. Upon direct injection of a mixture of 3,4-cyclohexenoesculetin beta-D galactopyranoside and ferric ammonium citrate, intense contrast was observed immediately in MCF7-lacZ tumors, but not in wild-type tumors. 3,4 Cyclohexenoesculetin beta-D-galactopyranoside activation in combination with ferric ions introduces a novel approach for assaying enzyme activity by MRI in vivo. PMID- 20572147 TI - In vivo MR evaluation of the effect of the CCR2 antagonist on macrophage migration. AB - The CCR2 antagonist is a receptor antagonist for monocyte chemoattractant protein 1 and is known to be a potential anti-inflammatory therapeutic agent. Recently used optimized labeling techniques for superparamagnetic iron oxide, macrophage homing, and recruitment toward the infection site can be observed on in vivo MRI. This study details the effect of the CCR2 antagonist on the macrophage migration and the feasibility of in vivo MRI for assessing the inhibition of chemotactic activity by the CCR2 antagonist. On binding assay, the CCR2 antagonist inhibits the binding affinity of monocyte chemoattractant protein-1 to CCR2. Increased expression of messenger ribonucleic acid (mRNA) and expression of CCR2 and CD11b on the cellular surface, as induced by monocyte chemoattractant protein-1, was shown, and the effect of monocyte chemoattractant protein-1 on CCR2 and CD11b was restricted by the CCR2 antagonist. In a migration test using the transwell system, macrophages treated with the CCR2 antagonist showed significantly decreased chemotactic migration compared to that of wild-type macrophages. MR images of infected left calf muscles in 12 mice were obtained 24 h after administration of macrophages labeled with superparamagnetic iron oxide. MRI successfully demonstrated the effect of the CCR2 antagonist on the directional migration of macrophages. PMID- 20572148 TI - Preferential patterns of myocardial iron overload by multislice multiecho T*2 CMR in thalassemia major patients. AB - T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (global T*(2) <26 ms), subsequently divided into two groups: severe (global T*(2) <10 ms) and mild to moderate (global T*(2) between 10 and 26 ms) myocardial iron overload. A preferential pattern of iron store in anterior and inferior regions was detected in both groups. This pattern was preserved among the slices. The pattern could not be explained by additive susceptibility artifacts, negligible in heavily iron loaded patients. A significantly higher T*(2) value in the basal slice was found in patients with severe iron overload. In conclusion, a segmental T*(2) cardiac MR approach could identify early iron deposit, useful for tailoring chelation therapy and preventing myocardial dysfunction in the clinical setting. PMID- 20572149 TI - A high-throughput eight-channel probe head for murine MRI at 9.4 T. AB - Murine MRI studies are conducted on dedicated MR systems, typically equipped with ultra-high-field magnets (>or=4.7 T; bore size: approximately 12-25 cm), using a single transmit-receive coil (volume or surface coil in linear or quadrature mode) or a transmit-receive coil combination. Here, we report on the design and characterization of an eight-channel volume receive-coil array for murine MRI at 400 MHz. The array was combined with a volume-transmit coil and integrated into one probe head. Therefore, the animal handling is fully decoupled from the radiofrequency setup. Furthermore, fixed tune and match of the coils and a reduced number of connectors minimized the setup time. Optimized preamplifier design was essential for minimizing the noise coupling between the elements. A comprehensive characterization of transmit volume resonator and receive coil array is provided. The performance of the coil array is compared to a quadrature driven birdcage coil with identical sensitive volume. It is shown that the miniature size of the elements resulted in coil noise domination and therefore reduced signal-to-noise-ratio performance in the center compared to the quadrature birdcage. However, it allowed for 3-fold accelerated imaging of mice in vivo, reducing scan time requirements and thus increasing the number of mice that can be scanned per unit of time. PMID- 20572150 TI - Measurement of perfusion and permeability from dynamic contrast-enhanced MRI in normal and pathological vertebral bone marrow. AB - Dynamic contrast-enhanced MRI data in vertebral bone marrow (vBM) are currently analyzed with descriptive indices. The purpose of this study was to develop and evaluate a quantitative approach, considering the tissue composition of vBM. Therefore, a measurement of the water fraction, f(wat), and the precontrast relaxation times, T(10 wat), T(10 fat), was added to the routine protocol. Signal analysis was generalized by allowing for an arbitrary fraction of fat. Plasma flow, plasma volume, extraction flow, and interstitial volume were determined from dynamic contrast-enhanced-MRI data. Simulations were used to determine the sensitivity to the precontrast values and to retrospectively verify the choice of the sequence parameters. Measurements were performed in healthy vertebral bodies (n = 30) and lesions of 15 patients with vertebral fractures. Extraction flow (milliliters per 100 mL/min) provided the strongest normal/abnormal separation: mean (standard deviation) was 0.3 (0.8) in healthy vBM and 6(4) in the fractures. Neglecting the fat component and the approximated signal analysis using relative signal enhancement produced significant differences. We conclude that correcting for the fat component in the signal and parametrization by tracer-kinetic analysis is necessary to avoid misinterpretation and/or systematic errors. The quantitative analysis is equally well suited as a descriptive parameter for the differentiation between normal and abnormal vertebral bone marrow. PMID- 20572151 TI - QRS prolongation in myotonic muscular dystrophy and diffuse fibrosis on cardiac magnetic resonance. AB - Current noninvasive surrogates of cardiac involvement in myotonic muscular dystrophy have low positive predictive value for sudden death. We hypothesized that the cardiac MR signal-to-noise ratio variance (SNRV) is a surrogate of the spatial heterogeneity of myocardial fibrosis and correlates with electrocardiography changes in myotonic muscular dystrophy. The SNRV for contrast enhanced cardiac MR images was calculated over the entire left ventricle in 43 patients with myotonic muscular dystrophy. All patients underwent standard electrocardiography, and a subset of 23 patients underwent signal averaged electrocardiography. After correcting for body mass index, age, and ejection fraction, SNRV was predictive of QRS duration on standard electrocardiography (1.35-msec increased QRS duration/unit increase in SNRV, P < 0.001). SNRV was also predictive of the low-amplitude late-potential duration (1.49-msec increased low-amplitude late-potential duration/unit increase in SNRV, P < 0.001). Ten-fold cross-validation yielded an area under the receiver operating characteristic curve of 0.87 for the predictive value of SNRV for QRS duration greater than 120 msec. The SNRV of the left ventricle is associated with QRS prolongation, likely due to late depolarization of tissue within islands of patchy fibrosis. The association of SNRV with future clinical events warrants further study. PMID- 20572152 TI - Reduction of fast spin echo cusp artifact using a slice-tilting gradient. AB - A "featherlike" artifact, termed a cusp artifact, is sometimes seen along the phase-encoding direction in sagittal or coronal fast spin echo images. This artifact arises from the spins, at a location distant from the magnet isocenter, that are excited and aliased to the field of view because their precession frequency is similar to those at the isocenter. Such a situation is created due to a combination of excessive gradient nonlinearity and rapid change of the main magnetic field near the edge of the magnet where the artifact-producing spins are located. A novel technique is proposed to reduce this artifact, in which a fast spin echo pulse sequence is modified to slightly tilt the slice selected by the radiofrequency excitation pulse away from the slice selected by the radiofrequency refocusing pulses. At the edge of the field of view, the incomplete overlap between the slices selected by the excitation and refocusing pulses effectively reduces the signals from the artifact-prone region. In contrast, the slices overlap substantially within the field of view so that the signals are largely retained. This slice-tilting technique has been implemented on two commercial MRI scanners operating at 3.0 T and 1.5 T, respectively, and evaluated on phantoms and human spine and extremities using clinical protocols. Both phantom and human results showed that the technique decreased the strength of the cusp artifact by at least 65% and substantially limited the spatial extent of the artifact. This technique, which can be further enhanced by a simple postprocessing step, offers significant advantages over a number of other techniques for reducing the fast spin echo cusp artifact. It can be implemented on virtually any scanner without hardware modification, complicated calibration, sophisticated image reconstruction, or patient-handling alteration. PMID- 20572154 TI - Active microcoil tracking in the lungs using a semisolid rubber as signal source. AB - A new method to localize and track medical devices in air-filled body cavities is proposed that uses active microcoils with a semisolid filling. In air spaces, e.g., the lung, microcoils require an independent signal source, which should be made of a biocompatible, solid and sterilizable material with a long shelf time. In a measurement of the T(1) and T*(2) and the relative spin density of several semisolid materials, latex was identified as a suitable material from which a prototype catheter was constructed with a microcoil at its tip. In a dual-echo tracking pulse sequence, the very short T*(2) of the rubber material allowed suppressing the background signal from surrounding tissue with a subtraction technique and additional dephasing gradients. With a roadmapping reconstruction, the microcoil's trajectory could be visualized on a previously acquired reference image set with a tracking rate of up to 60 Hz at a spatial resolution of better than 2mm. In a real-time tracking implementation, an image update rate of 4 Hz was achieved by combining the tracking with a fast real-time imaging sequence. Both methods were successfully applied in vivo to track the catheter in the lung of a pig. PMID- 20572153 TI - Optimization and validation of methods for mapping of the radiofrequency transmit field at 3T. AB - MRI techniques such as quantitative imaging and parallel transmit require precise knowledge of the radio-frequency transmit field (B(1) (+)). Three published methods were optimized for robust B(1) (+) mapping at 3T in the human brain: three-dimensional (3D) actual flip angle imaging (AFI), 3D echo-planar imaging (EPI), and two-dimensional (2D) stimulated echo acquisition mode (STEAM). We performed a comprehensive comparison of the methods, focusing on artifacts, reproducibility, and accuracy compared to a reference 2D double angle method. For the 3D AFI method, the addition of flow-compensated gradients for diffusion damping reduced the level of physiological artifacts and improved spoiling of transverse coherences. Correction of susceptibility-induced artifacts alleviated image distortions and improved the accuracy of the 3D EPI imaging method. For the 2D STEAM method, averaging over multiple acquisitions reduced the impact of physiological noise and a new calibration method enhanced the accuracy of the B(1) (+) maps. After optimization, all methods yielded low noise B(1) (+) maps (below 2 percentage units), of the nominal flip angle value (p.u.) with a systematic bias less than 5 p.u. units. Full brain coverage was obtained in less than 5 min. The 3D AFI method required minimal postprocessing and showed little sensitivity to off-resonance and physiological effects. The 3D EPI method showed the highest level of reproducibility. The 2D STEAM method was the most time efficient technique. PMID- 20572155 TI - Simulation model for contrast agent dynamics in brain perfusion scans. AB - Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods. PMID- 20572156 TI - Spiralometry: computerized assessment of tremor amplitude on the basis of spiral drawing. AB - Spiral drawing has been used for the assessment of the impact of therapy on motor performance in various movement disorders (e.g. in Parkinson's disease, especially for tremor and hypokinesia). Nevertheless, there are only few guidelines available providing some kind of standardized interpretation. The published protocol with the highest standard is that of Bain and Findley. Kinetic tremor assessed by spiral drawing is not quantified by alternative approaches so far and is not even considered by most rating scales. However, kinetic tremor is quite common and represents a significant impairment in the everyday life of parkinsonian patients. More complex instrumental methods for the quantification of kinetic tremor have not been practical as they, e.g., require relatively expensive equipment or have an unfavourable effort/benefit ratio. We pursued an alternative approach, where we scan drawn spirals to a computer-algorithm that calculates the tremor amplitude. Our standardized method can be applied without difficulty in patients needing only paper and pencil. The evaluation is fully automated, and therefore, it is appropriate for the assessment of therapeutic efficacy in very large populations. The objectivity of the approach represents a significant advantage. In the actual paper, we present how we analyzed the original spirals published by Bain and Findley to validate our computerized assessment. We found a highly significant connection between both methods (explained variance: 88.9%). PMID- 20572157 TI - Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses. AB - Agmatine, a metabolite of L-arginine, is considered as a novel putative neurotransmitter. It has been detected in axon terminals that synapse with pyramidal cells in the hippocampus, a brain region that is critically involved in spatial learning and memory. However, the role of agmatine in learning and memory is poorly understood. Recently, we demonstrated water maze training-induced increases in tissue levels of agmatine in the CA1 subregion of the hippocampus. This finding has raised an issue whether an endogenous agmatine could directly participate in learning and memory processes as a neurotransmitter. In the present study, quantitative immunogold-labeling and electron-microscopical techniques were used to analyze the levels of agmatine in CA1 stratum radiatum (SR) terminals (n = 600) of male Sprague-Dawley rats that had been trained to find a hidden escape platform in the water maze (WM) task or forced to swim (SW) in the pool with no platform presented. Agmatine levels were significantly increased by ~85% in the synaptic terminals of SR of trained WM group compared with the SW control group (all P < 0.001). These results, for the first time, demonstrate spatial learning-induced elevation in agmatine levels at synapses in the hippocampus and provide evidence of its participation in learning and memory processing as a novel neurotransmitter. PMID- 20572159 TI - Dishevelled-1 and dishevelled-3 affect cell invasion mainly through canonical and noncanonical Wnt pathway, respectively, and associate with poor prognosis in nonsmall cell lung cancer. AB - Dishevelled (Dvl) family proteins are overexpressed in nonsmall cell lung cancer (NSCLC), but the correlation between Dvl overexpression and patient prognosis is not clear. The underlying mechanisms of Dvl-1 and Dvl-3 promoting lung cancer cell invasion require further research. We used immunohistochemistry to assess the presence of Dvl-1, Dvl-3, beta-catenin, and p120ctn, and compared their expression to the prognosis in 102 specimens from NSCLC patients. We also examined the effect of Dvl-1 and Dvl-3 on Tcf-dependent transcriptional activity, as well as on the invasiveness in A549 and LTEP-alpha-2 lung cancer cells. The results showed that Dvl-1 correlated to the abnormal expression of beta-catenin, while Dvl-3 correlated to p120ctn. Both Dvl-1 and Dvl-3 were related to the poor prognosis of patient. Dvl-1 overexpression enhanced the Tcf-dependent transcriptional activity and beta-catenin expression significantly. However, Dvl 3 had little effect on the Tcf-dependent transcriptional activity and beta catenin expression, which was accompanied by p38 and JNK phosphorylation. Furthermore, the invasiveness of Dvl-3-enhanced cells was inhibited by p38 and JNK inhibitors. Exogenous expression of both Dvl-1 and Dvl-3 increased the p120ctn protein expression, while only Dvl-3 upregulated p120ctn mRNA. We conclude that both protein and mRNA of Dvl-1 and Dvl-3 are overexpressed in NSCLC in a manner related to poor prognosis. Dvl-1 may affect the biological behavior of lung cancer cells mainly through beta-catenin (canonical Wnt pathway), while Dvl-3 mainly through p38 and JNK pathway (noncanonical Wnt pathway). PMID- 20572158 TI - Growth-stimulatory effect of resveratrol in human cancer cells. AB - Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations ( A, FAS -670 A > G, and FASL -844 C > T polymorphisms in a hospital-based case-control study of 353 patients diagnosed with RCC and 365 cancer-free controls in a Chinese population. Compared with CASP8 -652 ins/ins genotype, the del/del genotype had a significantly decreased RCC risk [adjusted odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.16-0.84]. For FAS -1377 G > A polymorphism, a significantly increased risk of RCC was found for AA (adjusted OR = 1.65, 95% CI = 1.03-2.64) and GA (adjusted OR = 1.41, 95% CI = 1.02-1.94) genotypes compared with GG genotype. When we combined these two polymorphisms together, we found that individuals carrying CASP8 -652 6N ins/del and FAS -1377 GG genotypes or CASP8 652 6N del/del and FAS -1377 GG genotypes were associated with a statistically significantly decreased risk of RCC (adjusted OR = 0.46, 95% CI = 0.24-0.88 and OR = 0.12, 95% CI = 0.02-0.58, respectively) compared with individuals carrying CASP8 -652 6N ins/ins and FAS -1377 AA genotypes. These results suggest that the CASP8 -652 6N ins/del and FAS -1377 G > A polymorphisms are involved in the susceptibility to developing RCC in Chinese populations. PMID- 20572165 TI - Maleimide-modified phosphonium ionic liquids: a template towards (multi)task specific ionic liquids. AB - The synthesis and characterization of several compounds representing a new class of multitask-specific phosphonium ionic liquids that contain a maleimide functionality is reported. The maleimide moiety of the ionic liquid (IL) is shown to undergo Michael-type additions with substrates containing either a thiol or amine moiety, thus, serving as a template to introduce wide structural diversity into the IL. Multitask-specific ILs are accessible by reaction of the maleimide with Michael donors that are capable of serving some function. As a model example to illustrate this concept, a redox active ferrocenyl thiol was incorporated and examined by cyclic voltammetry. Because the maleimide moiety is highly reactive to additions, the task-specific ionic liquids (TSILs) are prepared as the furan protected Diels-Alder maleimide. The maleimide moiety can then be liberated when required by simple heating. PMID- 20572166 TI - Switchable cucurbituril-bipyridine beacons. AB - 4-Aminobipyridine derivatives form strong inclusion complexes with cucurbit[6]uril, exhibiting remarkably large enhancements in fluorescence intensity and quantum yields. The remarkable complexation-induced pK(a) shift (DeltapK(a)=3.3) highlights the strong charge-dipole interaction upon binding. The reversible binding phenomenon can be used for the design of switchable beacons that can be incorporated into cascades of binding networks. This concept is demonstrated herein by three different applications: 1) a switchable fluorescent beacon for chemical sensing of transition metals and other ligands; 2) direct measurement of binding constants between cucurbit[6]uril and various nonfluorescent guest molecules; and 3) quantitative monitoring of biocatalytic reactions and determination of their kinetic parameters. The latter application is illustrated by the hydrolysis of an amide catalyzed by penicillin G acylase and by the elimination reaction of a beta-cabamoyloxy ketone catalyzed by aldolase antibody 38C2. PMID- 20572167 TI - The torsional barriers of 2-hydroxy- and 2-fluorobiphenyl: small but measurable. AB - By making use of a novel diastereotopicity probe, namely C(CF(3))(2)OH, it has been possible to measure by very low temperature (19)F NMR spectroscopy the elusive aryl-aryl rotation barriers of biphenyls bearing an OH or F group in one ortho position. The experimental values (5.4 and 4.4 kcal mol(-1), respectively) are matched by those from ab initio calculations (5.3 and 4.3 kcal mol(-1), respectively). PMID- 20572169 TI - The Wacker process: inner- or outer-sphere nucleophilic addition? New insights from ab initio molecular dynamics. AB - The Wacker process consists of the oxidation of ethylene catalyzed by a Pd(II) complex. The reaction mechanism has been largely debated in the literature; two modes for the nucleophilic addition of water to a Pd-coordinated alkene have been proposed: syn-inner- and anti-outer-sphere mechanisms. These reaction steps have been theoretically evaluated by means of ab initio molecular dynamics combined with metadynamics by placing the [Pd(C(2)H(4))Cl(2)(H(2)O)] complex in a box of water molecules, thereby resembling experimental conditions at low [Cl(-)]. The nucleophilic addition has also been evaluated for the [Pd(C(2)H(4))Cl(3)](-) complex, thus revealing that the water by chloride ligand substitution trans to ethene is kinetically favored over the generally assumed cis species in water. Hence, the resulting trans species can only directly undertake the outer-sphere nucleophilic addition, whereas the inner-sphere mechanism is hindered since the attacking water is located trans to ethene. In addition, all the simulations from the [Pd(C(2)H(4))Cl(2)(H(2)O)] species (either cis or trans) support an outer sphere mechanism with a free-energy barrier compatible with that obtained experimentally, whereas that for the inner-sphere mechanism is significantly higher. Moreover, additional processes for a global understanding of the Wacker process in solution have also been identified, such as ligand substitutions, proton transfers that involve the aquo ligand, and the importance of the trans effect of the ethylene in the nucleophilic addition attack. PMID- 20572168 TI - [4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo dienophiles: stereoelectronic effects, anticancer properties and application to the synthesis of 7,8-substituted bicyclo[4.2.0]octa-2,4-dienes. AB - A detailed examination of [4+2] cycloaddition reactions between 1,8-disubstituted cyclooctatetraenes and diazo compounds revealed that 4-phenyl-1,2,4-triazole-3,5 dione (PTAD) reacts to form either 2,3- or 3,4-disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8-disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa-2,4-diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types. PMID- 20572170 TI - Theoretical design of high-spin polycyclic hydrocarbons. AB - High-spin organic structures can be obtained from fused polycyclic hydrocarbons, by converting selected peripheral HC(sp(2)) sites into H(2)C(sp(3)) ones, guided by Ovchinnikov's rule. Theoretical investigation is performed on a few examples of such systems, involving three to twelve fused rings, and maintaining threefold symmetry. Unrestricted DFT (UDFT) calculations, including geometry optimizations, confirm the high-spin multiplicity of the ground state. Spin-density distributions and low-energy spectra are further studied through geometry dependent Heisenberg-Hamiltonian diagonalizations and explicit correlated ab initio treatments, which all agree on the high-spin character of the suggested structures, and locate the low-lying states at significantly higher energies. In particular, the lowest-lying state of lower multiplicity is always found to be higher than kT at room temperature (at least ten times higher). Simplification of the ferromagnetic organization based on sets of semilocalized nonbonding orbitals is proposed. Molecular architectures are thus conceived in which the ferromagnetically-coupled unpaired electrons tally up to one third of the involved conjugated carbons. Connecting such building blocks should provide bidimensional materials endowed with robust magnetic properties. PMID- 20572171 TI - Mechanisms of singlet-oxygen and superoxide-ion generation by porphyrins and bacteriochlorins and their implications in photodynamic therapy. AB - New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction. PMID- 20572172 TI - Sonication-triggered instantaneous gel-to-gel transformation. AB - Two new peptide-based isomers containing cholesterol and naphthalic groups have been designed and synthesized. We found that the position of L-alanine in the linker could tune the gelation properties and morphologies. The molecule with the L-alanine residue positioned in the middle of the linker (1b) shows better gelation behavior than that with L-alanine directly linked to the naphthalimido moiety (1a). As a result, a highly thermostable organogel of 1b with a unique core-shell structure was obtained at high temperature and pressure in acetonitrile. Moreover, the gels of 1a and 1b could undergo an instantaneous gel to-gel transition triggered by sonication. Ultrasound could break the core-shell microsphere of 1b and the micelle structure of 1a into entangled fibers. By studying the mechanism of the sonication-triggered gel-to-gel transition process of these compounds, it can be concluded that ultrasound has a variety of effects on the morphology, such as cutting, knitting, unfolding, homogenizing, and even cross-linking. Typically, ultrasound can cleave and homogenize pi-stacking and hydrophobic interactions among the gel molecules and then reshape the morphologies to form a new gel. This mechanism of morphology transformation triggered by sonication might be attractive in the field of material storage and controlled release. PMID- 20572173 TI - Sonochemical preparation of hierarchical ZnO hollow spheres for efficient dye sensitized solar cells. AB - Hierarchical ZnO hollow spheres (400-500 nm in diameter) consisting of ZnO nanoparticles with a diameter of approximately 15 nm have been successfully prepared by a facile and rapid sonochemical process. The formation of hierarchical ZnO hollow spheres is attributed to the oriented attachment and subsequent Ostwald ripening process according to time-dependent experiments. The as-prepared ZnO hollow spheres are used as a photoanode in dye-sensitized solar cells and exhibit a highly efficient power conversion efficiency of 4.33%, with a short-circuit current density of 9.56 mA cm(-2), an open-circuit voltage of 730 mV, and a fill factor of 0.62 under AM 1.5 G one sun (100 mW cm(-2)) illumination. Moreover, the photovoltaic performance (4.33%) using the hierarchical ZnO hollow spheres is 38.8% better than that of a ZnO nanoparticle photoelectrode (3.12%), which is mainly attributed to the efficient light scattering for the former. PMID- 20572174 TI - A bevel-gear-shaped rotor bearing a double-decker porphyrin complex. PMID- 20572175 TI - Studies of 2-azaazulenium derivatives: unsymmetrical trimethine cyanine dyes bearing a 2-azaazulenium moiety as one of the terminal groups. AB - We report here the synthesis of a series of symmetrical and unsymmetrical trimethine cyanine dyes derived from 2-azaazulene, combined spectral and quantum chemical investigations of their molecular geometry and electron structure, as well as the nature of the lowest electron transitions. Based on the analysis of both calculations and experimental data obtained from absorption and (13)C NMR spectra, it was concluded that the 2-azaazulene residue can be treated as a weakly basic terminal group; its donor properties are provided with the participation of the HOMO-1, in contrast to the typical Brooker's terminal residues with their donor HOMOs. The new classification of the terminal groups of cyanine dyes, and hence the classification of types of unsymmetrical cyanines, is proposed. It is shown that the nature of the higher electron transitions (delocalized or local) in the cyanine dyes depends on their type. In the unsymmetrical trimethine cyanine of the mixed type, negative deviations are observed in their absorption spectra. PMID- 20572176 TI - Electroactive benzothiazole hydrazones and their [Mo6O19]2- derivatives: promising building blocks for conducting molecular materials. AB - The electroactive benzothiazole hydrazone AMBTH-H(2), a new member of the 2,2' azino-bis(N-alkylbenzothiazole) family, was synthesised in a five-step procedure and characterised by using X-ray diffraction along with two intermediates and the N-methylbenzothiazole hydrazone MBTH-H(2). Both AMBTH-H(2) and MBTH-H(2) were coupled to [Mo(6)O(19)](2-) in acetonitrile in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine to give two new diazoalkane hexamolybdates, which were isolated as tetrabutylammonium salts and characterised by using IR, UV/Vis and NMR spectroscopies, cyclic voltammetry and, for one of them, X-ray diffraction. The packing arrangement molecules in crystals of AMBTH H(2), the redox features of the AMBTH-hexamolybdate hybrid together with a good electronic communication between the organic pi system and the molybdenum centres make these compounds very promising blocks for the synthesis of conducting molecular materials. PMID- 20572177 TI - Cationic reverse micelles create water with super hydrogen-bond-donor capacity for enzymatic catalysis: hydrolysis of 2-naphthyl acetate by alpha-chymotrypsin. AB - Reverse micelles (RMs) are very good nanoreactors because they can create a unique microenvironment for carrying out a variety of chemical and biochemical reactions. The aim of the present work is to determine the influence of different RM interfaces on the hydrolysis of 2-naphthyl acetate (2-NA) by alpha chymotrypsin (alpha-CT). The reaction was studied in water/benzyl-n hexadecyldimethylammonium chloride (BHDC)/benzene RMs and, its efficiency compared with that observed in pure water and in sodium 1,4-bis-2 ethylhexylsulfosuccinate (AOT) RMs. Thus, the hydrolysis rates of 2-NA catalyzed by alpha-CT were determined by spectroscopic measurements. In addition, the method used allows the joint evaluation of the substrate partition constant K(p) between the organic and the micellar pseudophase and the kinetic parameters: catalytic rate constant k(cat), and the Michaelis constant K(M) of the enzymatic reaction. The effect of the surfactant concentration on the kinetics parameters was determined at constant W(0)=[H(2)O]/[surfactant], and the variation of W(0) with surfactant constant concentration was investigated. The results show that the classical Michaelis-Menten mechanism is valid for alpha-CT in all of the RMs systems studied and that the reaction takes place at both RM interfaces. Moreover, the catalytic efficiency values k(cat)/K(M) obtained in the RMs systems are higher than that reported in water. Furthermore, there is a remarkable increase in alpha-CT efficiency in the cationic RMs in comparison with the anionic system, presumably due to the unique water properties found in these confined media. The results show that in cationic RMs the hydrogen-bond donor capacity of water is enhanced due to its interaction with the cationic interface. Hence, entrapped water can be converted into "super-water" for the enzymatic reaction studied in this work. PMID- 20572178 TI - Effect of the nature of the substituent in N-alkylimidazole ligands on the outcome of deprotonation: ring opening versus the formation of N-heterocyclic carbene complexes. AB - Complexes [Re(CO)(3)(N-RIm)(3)]OTf (N-RIm=N-alkylimidazole, OTf=trifluoromethanesulfonate; 1a-d) have been straightforwardly synthesised from [Re(OTf)(CO)(5)] and the appropriate N-alkylimidazole. The reaction of compounds 1a-d with the strong base KN(SiMe(3))(2) led to deprotonation of a central C-H group of an imidazole ligand, thus affording very highly reactive derivatives. The latter can evolve through two different pathways, depending on the nature of the substituents of the imidazole ligands. Compound 1a contains three N-MeIm ligands, and its product 2a features a C-bound imidazol-2-yl ligand. When 2a is treated with HOTf or MeOTf, rhenium N-heterocyclic carbenes (NHCs) 3a or 4a are afforded as a result of the protonation or methylation, respectively, of the non coordinated N atom. The reaction of 2a with [AuCl(PPh(3))] led to the heterobimetallic compound 5, in which the N-heterocyclic ligand is once again N bound to the Re atom and C-coordinated to the gold fragment. For compounds 1b-d, with at least one N-arylimidazole ligand, deprotonation led to an unprecedented reactivity pattern: the carbanion generated by the deprotonation of the C2-H group of an imidazole ligand attacks a central C-H group of a neighbouring N-RIm ligand, thus affording the product of C-C coupling and ring-opening of the imidazole moiety that has been attacked (2c, d). The new complexes featured an amido-type N atom that can be protonated or methylated, thus obtaining compounds 3c, d or 4c, d, respectively. The latter reaction forces a change in the disposition of the olefinic unit generated by the ring-opening of the N-RIm ligand from a cisoid to a transoid geometry. Theoretical calculations help to rationalise the experimental observation of ring-opening (when at least one of the substituents of the imidazole ligands is an aryl group) or tautomerisation of the N-heterocyclic ligand to afford the imidazol-2-yl product. PMID- 20572179 TI - First dinuclear copper/gallium complexes: supporting Cu0 and Cu(I) centres by low valent organogallium ligands. AB - The synthesis and structural characterisation of low-valent dinuclear copper(I) and copper(0) complexes supported by organogallium ligands has been accomplished for the first time by the reductive coordination reaction of [GaCp*] (Cp*=pentamethylcyclopentadienyl) and [Ga(ddp)] (ddp=HC(CMeNC(6)H(3)-2,6 iPr(2))(2) 2-diisopropylphenylamino-4-diisopropylphenylimino-2-pentene) with readily available copper(II) and copper(I) precursors. The treatment of CuBr(2) and Cu(OTf)(2) (OTf=CF(3)SO(3)) with [Ga(ddp)] under mild conditions resulted in elimination of [Ga(L)(2)(ddp)] (L=Br, OTf) and afforded the novel gallium(I)/copper(I) compounds [{(ddp)GaCu(L)}(2)] (L=Br (1), OTf (2)). The single-crystal X-ray structure determinations of 1 and 2 reveal that these molecules are composed of {(ddp)GaCu(L)} dimeric units, with planar Cu(I)-Ga(I) four-membered rings and short Cu(I)...Cu(I) distances, with 2 exhibiting the shortest Cu(I)Cu(I) contact reported to date of 2.277(3) A. The all-gallium coordinated dinuclear [Cu(2)(GaCp*)(mu-GaCp*)(3)Ga(OTf)(3)] (3) is formed when Cu(OTf)(2) is combined with [GaCp*] instead of [Ga(ddp)]. Notably, in the course of this redox reaction Lewis acidic Ga(OTf)(3) is formed, which coordinates to one of the electron-rich copper(0) centres. Compound 3 is suggested as the first case of a structurally characterised complex of copper(0). By changing the copper(II) to a copper(I) source, that is, [Cu(cod)(2)][OTf] (cod=1,5 cyclooctadiene), the salt [Cu(2)(GaCp*)(3)(mu-GaCp*)(2)][OTf](2) (4) is formed, the cationic part of which is related to previously described isoelectronic dinuclear d(10) complexes of the type [M(2)(GaCp*)(5)] (M=Pd, Pt). PMID- 20572180 TI - Preparation of organoaluminum reagents from propargylic bromides and aluminum activated by PbCl2 and their regio- and diastereoselective addition to carbonyl derivatives. AB - Various propargylic and allenic aluminum reagents have been easily prepared by a direct insertion of aluminum into propargylic bromides in the presence of PbCl(2) (1 mol%). These organoaluminum reagents react with carbonyl compounds to afford the corresponding allenic alcohols or homopropargylic alcohols in good to excellent yields with high regio- and diastereoselectivity. PMID- 20572181 TI - Reactivity of the latent 12-electron fragment [Rh(PiBu3)2]+ with aryl bromides: aryl-Br and phosphine ligand C-H activation. AB - Oxidative addition of aryl bromides to 12-electron [Rh(PiBu(3))(2)][BAr(F)(4)] (Ar(F)=3,5-(CF(3))(2)C(6)H(3)) forms a variety of products. With p-tolyl bromides, Rh(III) dimeric complexes result [Rh(PiBu(3))(2)(o/p-MeC(6)H(4))(mu Br)](2)[BAr(F)(4)](2). Similarly, reaction with p-ClC(6)H(4)Br gives [Rh(PiBu(3))(2)(p-ClC(6)H(4))(mu-Br)](2)[BAr(F)(4)](2). In contrast, the use of o BrC(6)H(4)Me leads to a product in which toluene has been eliminated and an isobutyl phosphine has undergone C-H activation: [Rh{PiBu(2)(CH(2)CHCH(3)CH(2))}(PiBu(3))(mu-Br)](2)[BAr(F)(4)](2). Trapping experiments with ortho-bromo anisole or ortho-bromo thioanisole indicate that a possible intermediate for this process is a low-coordinate Rh(III) complex that then undergoes C-H activation. The anisole and thioanisole complexes have been isolated and their structures show OMe or SMe interactions with the metal centre alongside supporting agostic interactions, [Rh(PiBu(3))(2)(C(6)H(4)OMe)Br][BAr(F)(4)] (the solid-state structure of the 5 methyl substituted analogue is reported) and [Rh(PiBu(3))(2)(C(6)H(4)SMe)Br][BAr(F)(4)]. The anisole-derived complex proceeds to give [Rh{PiBu(2)(CH(2)CHCH(3)CH(2))}(PiBu(3))(mu-Br)](2)[BAr(F)(4)](2), whereas the thioanisole complex is unreactive. The isolation of [Rh(PiBu(3))(2)(C(6)H(4)OMe)Br][BAr(F)(4)] and its onward reactivity to give the products of C-H activation and aryl elimination suggest that it is implicated on the pathway of a sigma-bond metathesis reaction, a hypothesis strengthened by DFT calculations. Calculations also suggest that C-H bond cleavage through phosphine assisted deprotonation of a non-agostic bond is also competitive, although the subsequent protonation of the aryl ligand is too high in energy to account for product formation. C-H activation through oxidative addition is also ruled out on the basis of these calculations. These new complexes have been characterised by solution NMR/ESIMS techniques and in the solid-state by X-ray crystallography. PMID- 20572182 TI - Preparation of imidazolin-2-iminato molybdenum and tungsten benzylidyne complexes: a new pathway to highly active alkyne metathesis catalysts. AB - The reaction of [PhC[triple bond]MBr(3)(dme)] (dme=1,2-dimethoxyethane) with the hexafluoro-tert-butoxides LiX or KX [X=OC(CF(3))(2)Me] afforded the benzylidyne complexes [PhC[triple bond]MX(3)(dme)] (2a: M=W, 2b: M=Mo), which further reacted with the lithium reagent Li(Im(tBu)N), generated with MeLi from 1,3-di-tert butylimidazolin-2-imine (Im(tBu)NH), to form the imidazolin-2-iminato complexes [PhC[triple bond]MX(2)(Im(tBu)N)] (3a: M=W, 3b: M=Mo). The propylidyne complex [EtC[triple bond]MoX(2)(NIm(tBu))] (4) was obtained by treatment of 3b with an excess of 3-hexyne. Complexes 3a and 3b are able to efficiently catalyse alkyne cross metathesis of various 3-pentynyl benzyl ethers 5 and benzoic esters 7 at room temperature, to afford 2-butyne and the corresponding diethers 6 and diesters 8. The tungsten complex 3a proved to be a superior catalyst for ring closing alkyne metathesis, and the [10]cyclophanes 10 and 12 were synthesised in high yield from 1,3-bis(3-pentynyloxymethyl)benzene (9) and bis(3-pentynyl) phthalate (11), respectively. The molecular structures of compounds 2a, 2b, 3a, 3b, 4, and 12 were determined by single-crystal X-ray diffraction. DFT calculations have been carried out for catalyst systems based on the imidazolin-2 iminato tungsten and molybdenum complexes 3a and 3b by choosing the alkyne metathesis of 2-butyne as the model reaction; the studies revealed a lower activation barrier for the tungsten system. PMID- 20572183 TI - Ferrocene-substituted dithio-o-carborane isomers: influence on the native conformation of myoglobin protein. AB - Biointeractions between two organometallic compounds, a pair of ferrocene substituted dithio-o-carborane isomers (C(14)H(20)B(10)FeS(2); denoted as FcSB1 and FcSB2), and myoglobin (Mb) have been investigated by means of electrochemistry, fluorescence, circular dichroism, and UV/Vis absorption spectroscopy. Our observations demonstrate that FcSB1 and FcSB2 could coordinate to the axial position trans to the histidine imidazole that induces the change of the heme iron from the high spin state to the low spin state and the changes of the conformation of the aromatic fluorophores of the selected heme protein. Such influences attribute to the structural features of FcSB1 and FcSB2 containing sulfur donor atoms and hydrophobic ferrocenyl and carboranyl units that leads to specific binding modalities with Mb. This study provides an insight into the understanding of relevant biointeractions between the new type of ferrocene carborane conjugates and hemoproteins, and might shed light on the promising bioapplications of these multifunctional organometallic complexes. PMID- 20572184 TI - Pyrrole and oligopyrrole synthesis by 1,3-dipolar cycloaddition of azomethine ylides with sulfonyl dipolarophiles. AB - A procedure for the synthesis of functionalized, substituted pyrroles by 1,3 dipolar cycloaddition of azomethine ylides has been developed. This protocol is based on the metal-catalyzed cycloaddition of alpha-iminoesters with sulfonyl dipolarophiles, followed by the base-promoted elimination of the sulfonyl groups. A wide variety of 2,5-disubstituted and 2,3,5- and 2,4,5-trisubstituted pyrroles have been prepared in satisfactory yields from 1,2-bis(sulfonyl ethylene), beta sulfonylenones, and beta-sulfonylacrylates. This method can be applied in an iterative and straightforward manner to the construction of oligopyrroles, from bipyrroles to pentapyrroles. Iterative [n+1] and [n+2] approaches have been devised, the latter involves double 1,3-dipolar cycloaddition from pyrrolyl-based bis(iminoesters). PMID- 20572185 TI - An alternative mechanistic concept for homogeneous selective ethylene oligomerization of chromium-based catalysts: binuclear metallacycles as a reason for 1-octene selectivity? AB - An alternative concept for the selective catalytic formation of 1-octene from ethylene via dimeric catalytic centers is proposed. The selectivity of the tetramerization systems depends on the capability of ligands to form binuclear complexes that subsequently build up and couple two separate metallacyclopentanes to form 1-octene selectively. Comparison of existing catalytic processes, the ability of the bis(diarylphosphino)amine (PNP) ligand to bridge two metal centers, and the experimental background support the proposed binuclear mechanism for ethylene tetramerization. PMID- 20572186 TI - Imination of sulfides and sulfoxides with sulfonylimino-lambda3-bromane under mild, metal-free conditions. AB - Exposure of sulfides and sulfoxides to trifluoromethanesulfonylimino(aryl) lambda(3)-bromane in dichloromethane at 0 degrees C results in a facile transfer of the sulfonylimino group to sulfur atoms and affords N-triflylsulfilimines and sulfoximines in high yields under transition-metal-free conditions. Imination of (R)-methyl p-tolyl sulfoxide proceeded with predominant retention of configuration at the stereogenic sulfur center. The Hammett plot afforded rho values of -0.58 for para-substituted thioanisoles and -0.49 for their equivalent sulfoxides, which suggests a buildup of positive charge on the sulfur atoms of sulfides and sulfoxides in the transition state. Calculations suggest a bimolecular nucleophilic-substitution mechanism on the negatively charged nitrogen atom of the sulfonylimino-lambda(3)-bromane, which involves the attack of a sulfide from the opposite side to bromine(III). PMID- 20572187 TI - Proton-transfer reactions on hexanuclear platinum clusters: reversible heterolytic cleavage of H2 and C-H activation affording a linear, cluster containing polymer. AB - The hexanuclear cluster {Pt(6)}H(2) (2) contains a sterically hindered and chemically stable {Pt(6)} = Pt(6)(mu-PtBu(2))(4)(CO)(4) core, with the six metals forming an edge-bridged tetrahedron. The two hydrides are the reactive sites of the cluster and lie on opposite sides of the cluster, terminally bonded to the two "apical" edge-bridging platinum centres. Indeed, cluster 2 reacts with acids of different acidity (HA = CF(3)SO(3)H, HBF(4), p-CH(3)-C(6)H(4)-SO(3)H, CF(3)COOH, PhCOOH and CH(3)COOH), affording, after evolution of two equivalents of dihydrogen, the corresponding anion-substituted clusters {Pt(6)}A(2) (4). We suggest that the reaction proceeds through a mechanism similar to the one generally accepted for the analogous protonation of mononuclear hydrides, with some of the intermediates partially characterised at low temperature. Interestingly, the reverse reaction, the heterolytic splitting of H(2) by clusters 4, occurs readily under mild conditions. The anions in clusters 4a and 4b (4a: A = CF(3)SO(3), 4b: A = BF(4)) are bonded in the solid state but very easily dissociate in solution and may be substituted under mild conditions by weak ligands, such as CH(2)Cl(2) or CH(3)CN. With dialkyl ethers, the reaction proceeds further with the heterolytic splitting of a C-H bond of the ethereal ligand. This process allowed us to isolate the polymer [{Pt(6)}(CH(2)OCH(2)CH(2)OCH(2))](x) (8), in which the {Pt(6)} cluster units are connected by insulating spacers arising from dimethoxyethane. The results of single-crystal X-ray diffraction studies on 4a and 8 are also reported. PMID- 20572188 TI - Contributions of electron microscopy to understanding CO adsorption on powder Au/ceria-zirconia catalysts. AB - The influence of the highly dispersed gold phase on the CO-support interaction occurring in two 2.5 wt % Au/Ce(0.62)Zr(0.38)O(2) catalysts with medium (Au/CZ MD) and high (Au/CZ-HD) metal dispersion is quantitatively assessed. For this purpose, we have followed an approach in which high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), computer modelling, volumetric adsorption and FTIR spectroscopy studies are combined. This approach has already been fruitfully applied to the investigation of the specific CO-metal adsorption in Au/ceria-zirconia catalysts. As deduced from the experimental studies reported herein, the presence of gold dramatically increases the amount of CO strongly chemisorbed on the support. Moreover, this amount is sensitive to the metal dispersion, thus suggesting the occurrence of a mechanism in which the CO molecules that are initially adsorbed on the gold nanoparticles are further transferred to the support by means of a spillover process. An annular model is proposed for the growth of the CO phase adsorbed on the ceria-zirconia mixed oxide in the presence of Au. By assuming this model, we have estimated the width of the annulus, Delta r, of the adsorbed CO grown around the Au nanoparticles in Au/CZ-MD and Au/CZ-HD catalysts. This value is found to be very close to Delta r approximately 2 nm in both cases, the coincidence lending some additional support to the model. To further confirm this proposal, we have investigated the influence of CO pre-adsorption on the D(2)-Au/CZ-MD interaction, at 298 K. As revealed by FTIR spectroscopy, the kinetics of the deuterium spillover is significantly disturbed by the pre-adsorbed CO, which is fully consistent with an annular model for the CO adsorption. We conclude from the global analysis of the results reported here and those already available on CO-Au adsorption that the appropriate combination of nanostructural, computer modelling and chemical techniques is a powerful tool allowing us to gain a comprehensive picture of the complex series of processes involved in the CO adsorption on this relevant family of gold catalysts. PMID- 20572189 TI - Rhodium-catalyzed synthesis of gamma-pyrones by three consecutive redox-aldol reactions of allylic alcohols with alpha,beta-unsaturated aldehydes. PMID- 20572190 TI - Concise modular asymmetric synthesis of deguelin, tephrosin and investigation into their mode of action. PMID- 20572191 TI - A micelle-based chemosensing ensemble for the fluorimetric detection of chloride in water. PMID- 20572192 TI - Total synthesis and structural revision of biyouyanagin B. PMID- 20572193 TI - Investigating the effect of aqueous extract of Chicorium intybus L. leaves on offspring sex ratio in rat. AB - A traditional belief in Iranian culture indicates that parental consumption of chicory leaves (Chicorium intybus L.) affects the gender of newborns. The aim of this study was to investigate the effect of aqueous extract of chicory on offspring sex ratio in rat. All rats in experimental groups 1 and 2 were i.p. injected with either 1.0 or 0.7 g/kg body weight (LD50 = 2.244 g/kg) of an aqueous extract of chicory leaves for 30 days at 72 h intervals. The control rats were injected with distilled water in the same manner. After the 8th injection, blood pH, and Na(+), K(+), Ca(2+) and Mg(2+) serum levels, were measured in all groups. On day 30, all the rats were mated within and between groups. The results revealed that in comparison with the control group, there were significant increases (p < 0.01) in Na(+) and K(+) levels, as well as the sex ratio of male to female offspring (10.23%) in experimental group 1. Therefore, it can be concluded that the administration of chicory leaf extract has a significant effect on the sex ratio of the rat offspring. PMID- 20572194 TI - The clinical effectiveness of chokeberry: a systematic review. AB - Products derived from the black chokeberry, Aronia melanocarpa, are claimed to be beneficial in disorders or diseases associated with oxidative stress. The claims are based on evidence from in vitro studies and animal experiments. The active principle--a mixture of procyanidins, anthocyanins and phenolic acids- constitutes one of the most potent natural antioxidants. A systematic review was carried out of the quality of the clinical trials on chokeberry products that had been published up to December 2009, and conventionally established criteria were used to assess the strength of the evidence for their clinical effectiveness. Thirteen studies were identified. The quality of most of the trials and, correspondingly, the evidence of effectiveness for Aronia products is poor. Though laboratory and clinical data indicate that chokeberry products may well be useful as 'functional food' for disorders or diseases related to oxidative stress, these promising indications need to be confirmed in more rigorous studies before putative therapeutic uses can be confidently recommended for chokeberry products. PMID- 20572195 TI - Late phase of long-term potentiation in the mossy fiber-CA3 hippocampal pathway is critically dependent on metalloproteinases activity. AB - Matrix metalloproteinases (MMPs) are known to play a pivotal role in remodeling of the extracellular matrix and have been implicated in synaptic plasticity, learning and memory. In hippocampus, inhibition of MMPs impairs the maintenance of long term plasticity in Schaeffer collateral-CA1 (Sch/CA1) synapses while its effect on short term plasticity remains a matter of debate. Surprisingly little is known on the role of MMPs in other hippocampal synapses. In this study we have investigated the impact of a broad spectrum MMPs inhibitor, FN-439 on synaptic transmission in mossy fiber-CA3 (MF/CA3) synapses exhibiting profoundly different mechanism of long term potentiation (LTP) as well as robust short-term plasticity, features that clearly distinguish them from the Sch/CA1 synapses. We report, that MMPs blockade before and up to 30 minutes after LTP induction resulted in a severe disruption of the late phase of tetanically induced LTP. However, LTP time course was not changed when FN439 was administered 60 minutes post LTP induction indicating that MMPs activity is required for the consolidation of the synaptic plasticity within a specific time window. The paired-pulse facilitation ratio or post-tetanic potentiation or burst-like pattern of mossy fiber stimulation were not changed in the presence of FN-439 administered for 15 minutes suggesting that temporal pattern of presynaptic transmitter release and, in general, the MF-CA3 fidelity is not significantly affected by MMPs inhibition. We conclude that although the mechanisms of long term plasticity in MF/CA3 and in Sch/CA1 are profoundly different, MMPs play a crucial role in both pathways in the maintenance of LTP, which is believed to play an important role in learning and memory in the hippocampus. PMID- 20572196 TI - Lesions of reuniens and rhomboid thalamic nuclei impair radial maze win-shift performance. AB - The reuniens (Re) and rhomboid (Rh) nuclei are major sources of thalamic input to hippocampus and medial prefrontal cortex. We compared effects of lesions in ReRh and other parts of the midline-intralaminar complex on tasks affected by lesions in terminal fields innervated by these nuclei, including: visuospatial reaction time (VSRT), a measure of sensory guided responding; serial VSRT, a measure of action sequence learning; and win/shift radial arm maze (RAM) measures of spatial memory. ReRh lesions affected RAM, but not VSRT or serial VSRT performance. The effects of caudal intralaminar lesions were doubly dissociated from ReRh lesions, affecting VSRT, but not RAM or serial VSRT performance. Rostral intralaminar lesions did not produce significant impairments, other than a subgroup with larger lesions that were impaired performing a delayed RAM task. Combined lesions damaging all three sites produced RAM deficits comparable to ReRh lesions and VSRT deficits comparable to caudal intralaminar lesions. Thus there was no indication that deficits produced by lesions in one site were exacerbated significantly by the cumulative effect of damage in other parts of the midline intralaminar complex. The effects of ReRh lesions provide evidence that these nuclei affect memory functions of hippocampus and medial prefrontal cortex. The double dissociation observed between the effects of ReRh and caudal intralaminar nuclei provides evidence that different nuclei within the midline-intralaminar complex affect distinct aspects of cognition consistent with the effects of lesions in the terminal fields they innervate. PMID- 20572198 TI - Hippocampal astrocytes are necessary for antidepressant treatment of learned helplessness rats. AB - The astrocyte is a major component of the neural network and plays a role in brain function. Previous studies demonstrated changes in the number of astrocytes in depression. In this study, we examined alterations in the number of astrocytes in the learned helplessness (LH) rat, an animal model of depression. The numbers of activated and nonactivated astrocytes in the dentate gyrus (molecular layer, subgranular zone, and hilus), and CA1 and CA3 regions of the hippocampus were significantly increased 2 and 8 days after attainment of LH. Subchronic treatment with imipramine showed a tendency (although not statistically significant) to decrease the LH-induced increment of activated astrocytes in the CA3 region and dentate gyrus. Furthermore, subchronic treatment of naive rats with imipramine did not alter the numbers of activated and nonactivated astrocytes. However, the antidepressant-like effects of imipramine in the LH paradigm were blocked when fluorocitrate (a reversible inhibitor of astrocyte function) was injected into the dentate gyrus or CA3 region. Injection of fluorocitrate into naive rats failed to induce behavioral deficits in the conditioned avoidance test. These results indicate that astrocytes are responsive to the antidepressant-like effect of imipramine in the dentate gyrus and CA3 region of the hippocampus. PMID- 20572197 TI - Structural and functional plasticity of the hippocampal formation in professional dancers and slackliners. AB - The acquisition of special skills can induce plastic changes in the human hippocampus, a finding demonstrated in expert navigators (Maguire et al. (2000) Proc Natl Acad Sci USA 97:4,398-403). Conversely, patients with acquired chronic bilateral vestibular loss develop atrophy of the hippocampus, which is associated with impaired spatial memory (Brandt et al. (2005) Brain 128:2,732-741). This suggests that spatial memory relies on vestibular input. In this study 21 professional dancers and slackliners were examined to assess whether balance training with extensive vestibulo-visual stimulation is associated with altered hippocampal formation volumes or spatial memory. Gray matter voxel-based morphometry showed smaller volumes in the anterior hippocampal formation and in parts of the parieto-insular vestibular cortex of the trained subjects but larger volumes in the posterior hippocampal formation and the lingual and fusiform gyri bilaterally. The local volumes in the right anterior hippocampal formation correlated negatively and those in the right posterior hippocampal formation positively with the amount of time spent training ballet/ice dancing or slacklining at the time of the study. There were no differences in general memory or in spatial memory as assessed by the virtual Morris water task. Trained subjects performed significantly better on a hippocampal formation-dependent task of nonspatial memory (transverse patterning). The smaller anterior hippocampal formation volumes of the trained subjects may be the result of a long-term suppression of destabilizing vestibular input. This is supported by the associated volume loss in the parieto-insular vestibular cortex. The larger volumes in the posterior hippocampal formation of the trained subjects might result from their increased utilization of visual cues for balance. This is supported by the concomitant larger volumes in visual areas like the lingual and fusiform gyri. Our findings indicate that there is a spatial separation of vestibular and visual processes in the human hippocampus. PMID- 20572199 TI - AMPA GluR-A receptor subunit mediates hippocampal responsiveness in mice exposed to stress. AB - Because stress represents a major precipitating event for psychiatric disorders, it is important to identify molecular mechanisms that may be altered in vulnerable individuals when exposed to stress. Here, we studied GluR-A(-/-) mice, animals with compromised AMPA receptor signaling, and characterized by a schizophrenic as well as depressive phenotype to investigate changes occurring in response to an acute stress. Wild-type and GluR-A(-/-) mice were exposed to a single immobilization stress and sacrificed immediately after the end of the stress for the analysis of activity regulated genes and of glutamatergic synapse responsiveness. The acute stress produced a marked increase in the hippocampal expression of Arc (activity-regulated cytoskeletal-associated protein) in GluR-A( /-) , but not in wild-type mice, which was associated with a similar increase of phospho-CaMKII, a partner in the action of Arc. When looking at the glutamatergic response to stress in wild-type animals, we found that stress increased GluR-A phosphorylation on serine831, an effect that was paralleled by a significant increase of the phosphorylation of the main NMDA receptor subunits, that is, NR-1 and NR-2B. Conversely, the stress-induced modulation of NMDA receptor subunits was not observed in GluR-A(-/-) mice. We suggest that enhanced stress responsiveness in GluR-A(-/-) mice may be due, at least in part, to their inability to activate NMDA-mediated glutamatergic neurotransmission, suggesting that the integrity of AMPA/NMDA receptor function may be important for successful coping under stressful conditions. PMID- 20572200 TI - Optimal cost reimbursement of health insurers to reduce risk selection. AB - In the absence of a perfect risk adjustment scheme, reimbursing health insurers' costs can reduce risk selection in community-rated health insurance markets. In this paper, we develop a model in which insurers determine the cost efficiency of health care and have incentives for risk selection. We derive the optimal cost reimbursement function, which balances the incentives for cost efficiency and risk selection. For health cost data from a Swiss health insurer, we find that an optimal cost reimbursement scheme should reimburse costs only up to a threshold. PMID- 20572201 TI - Internationally comparable health indices. AB - One of the most intractable problems in international health research is the lack of comparability of health measures across countries or cultures. We develop a cross-country measurement model for health, in which functional limitations, self reports of health, and a physical measure are interrelated to construct health indices. To establish comparability across countries, we define the measurement scales by the physical measure while other parameters vary by country to reflect cultural and linguistic differences in response patterns. We find significant cross-country variation in response styles of health reports along with variability in genuine health that is related to differences in national income. Our health indices achieve satisfactory reliability of about 80% and their gradients by age, income, and wealth for the most part show the expected patterns. Moreover, the health indices correlate much more strongly with income and net worth than self-reported health measures. PMID- 20572202 TI - MRT letter: Optimal composite depth function for 3D shape recovery of microscopic objects. AB - Generally, in shape from focus techniques, a single focus measure is used in estimating the three-dimensional structure of microscopic objects. However, the performance of a single focus measure is limited to estimate accurately the depth map of diverse type of objects. To cope with this problem, we propose genetic programming based novel approach by developing an optimal composite depth (OCD) function for accurate depth estimation. This OCD function optimally combines the initial depth and focus information extracted from individual focus measures. An improved performance of this function is reported for synthetic and real world microscopic objects. PMID- 20572203 TI - MRT letter: Spatial distribution of vancomycin-induced damage in Staphylococcus epidermidis biofilm: an electron microscopic study. AB - This study was planned to elucidate the efficacy of antibiotics on Staphylococcus epidermidis and Staphylococcus aureus biofilms by scanning electron microscopy (SEM). Biofilms of S. epidermidis ATCC 35984 and S. aureus ATCC 29213 were grown on black, polycarbonate membranes placed on tryptic soy agar plates for 48 h at 37 degrees C, and then exposed to vancomycin or amikacin or ciprofloxacin at clinically achievable levels for 24 h at 37 degrees C. The morphology of antibiotic-treated and untreated biofilms was elucidated by SEM. SEM analysis indicated a differential affection of S. epidermidis ATCC 35984 in the center and periphery of biofilm upon treatment with vancomycin. The center of biofilm revealed damaged cells with sparse distribution, smaller size, and irregular shape, whereas cells in the periphery were unaffected. This differential distribution of susceptibility within S. epidermidis ATCC 35984 biofilms was specific for vancomycin only and was not observed on exposure to amikacin or ciprofloxacin. No such response was found in S.aureus ATCC 29213 biofilms. Thus, our study suggests a spatial distribution of vancomycin-induced damage in S. epidermidis biofilms. To our knowledge, this is the first report that indicates a differential affection of S. epidermidis in the center and periphery of biofilm upon treatment with vancomycin. Studies on the factors controlling this differential distribution could provide valuable insights into the mechanisms of antimicrobial resistance in S. epidermidis biofilms. PMID- 20572204 TI - Synthesis and electron microscopic analysis of the self-assembly of polymer and ferritin core-shell structures. AB - Self-assembly of poly(4-vinylpyridine) (P4VP) and ferritin produced a spherical core-shell structure, which was analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In particular, for better understanding, the organization of such core-shell nanostructures, an optimal protocol for preparation of TEM thin sectioning of ferritin-P4VP composites, was developed. It entails fixing the ferritin-P4VP complex with 2.5% glutaraldehyde and infiltrating it with a mixture of acetone/resin while omitting the OsO(4) postfixation and ethanol dehydration steps of the conventional protocol. Using this method, a round-shaped thin section structure with unevenly distributed dark and white components was observed. The dark component from the thin section structure was determined to contain ferritin by energy-filtered TEM imaging and iron element mapping, whereas the white part was identified as P4VP by its energy dispersive X-ray spectroscopy (EDS) spectrum. PMID- 20572205 TI - Cryo-scanning electron microscopy and light microscopy for the study of fungi interactions. AB - The application of the cryo-scanning electron microscopy and light microscopy for the study of the interactions at different environmental conditions between Penicillium oxalicum and Fusarium verticillioides is described. A dual microculture was developed for the light microscopy analysis of the interaction. The microscope and macroscopic examinations were compared. Analysis of Petri plates revealed that F. verticillioides was a competitor for space and nutrients while P. oxalicum was a mycoparasite under the microscopic observations. PMID- 20572206 TI - Self-management strategies used by 'high functioning' individuals with bipolar disorder: from research to clinical practice. AB - INTRODUCTION: Bipolar disorder (BD) is a complex mental illness that results in substantial costs, both at a personal and societal level. Research into BD has been driven by a strongly medical model conception, with a focus upon pathology and dysfunction. Little research to date has focused upon strategies used to maintain or regain wellness in BD. Here, we present results from a qualitative study of self-management strategies used by a Canadian sample of 'high functioning' individuals with BD. The aims of the present paper are two-fold: (1) To provide a description of the self-management strategies identified as effective by this sample of high functioning individuals and 2) to explore these results from a clinical perspective. METHODS: High functioning (determined as a score of either 1 or 2 on the objectively-rated Multidimensional Scale of Independent Functioning) individuals with BD type I or II (N = 33) completed quantitative scales to assess depression, mania, psychosocial functioning and quality of life, and underwent either an individual interview or focus group about the self-management strategies they used to maintain or regain wellness. RESULTS: The specific self-management strategies that individuals enacted are contained within the following categories: (1) sleep, diet, rest and exercise; (2) ongoing monitoring; (3) reflective and meditative practices; (4) understanding BD and educating others; (5) connecting to others and (6) enacting a plan. These strategies are discussed in the context of current treatment interventions and research findings, offering clinicians a broad range of potential techniques or tools to assist with their efforts to support individuals with BD in maintaining or regaining wellness. CONCLUSIONS: The strategies adopted by a sample of people coping well with their BD show remarkable overlap with the targets of existing adjunctive psychosocial interventions for BD. The clinician can use this information to motivate clients to engage with such strategies. The present findings also serve to remind the clinician of significant individual differences in the personal meaning and concrete application of superficially similar strategies. PMID- 20572207 TI - Genetic patterns of correlation among subcortical volumes in humans: results from a magnetic resonance imaging twin study. AB - Little is known about genetic influences on the volume of subcortical brain structures in adult humans, particularly whether there is regional specificity of genetic effects. Understanding patterns of genetic covariation among volumes of subcortical structures may provide insight into the development of individual differences that have consequences for cognitive and emotional behavior and neuropsychiatric disease liability. We measured the volume of 19 subcortical structures (including brain and ventricular regions) in 404 twins (110 monozygotic and 92 dizygotic pairs) from the Vietnam Era Twin Study of Aging and calculated the degree of genetic correlation among these volumes. We then examined the patterns of genetic correlation through hierarchical cluster analysis and by principal components analysis. We found that a model with four genetic factors best fit the data: a Basal Ganglia/Thalamus factor; a Ventricular factor; a Limbic factor; and a Nucleus Accumbens factor. Homologous regions from each hemisphere loaded on the same factors. The observed patterns of genetic correlation suggest the influence of multiple genetic influences. There is a genetic organization among structures which distinguishes between brain and cerebrospinal fluid spaces and between different subcortical regions. Further study is needed to understand this genetic patterning and whether it reflects influences on early development, functionally dependent patterns of growth or pruning, or regionally specific losses due to genes involved in aging, stress response, or disease. PMID- 20572208 TI - Constrained principal component analysis reveals functionally connected load dependent networks involved in multiple stages of working memory. AB - Constrained principal component analysis (CPCA) with a finite impulse response (FIR) basis set was used to reveal functionally connected networks and their temporal progression over a multistage verbal working memory trial in which memory load was varied. Four components were extracted, and all showed statistically significant sensitivity to the memory load manipulation. Additionally, two of the four components sustained this peak activity, both for approximately 3 s (Components 1 and 4). The functional networks that showed sustained activity were characterized by increased activations in the dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex, and left supramarginal gyrus, and decreased activations in the primary auditory cortex and "default network" regions. The functional networks that did not show sustained activity were instead dominated by increased activation in occipital cortex, dorsal anterior cingulate cortex, sensori-motor cortical regions, and superior parietal cortex. The response shapes suggest that although all four components appear to be invoked at encoding, the two sustained-peak components are likely to be additionally involved in the delay period. Our investigation provides a unique view of the contributions made by a network of brain regions over the course of a multiple-stage working memory trial. PMID- 20572209 TI - Diffusion tensor imaging of white matter involvement in essential tremor. AB - This study set out to determine whether there is white matter involvement in essential tremor (ET), the most common movement disorder. We collected diffusion MRI and analysed differences in fractional anisotropy (FA) and mean diffusivity (MD) between ET patients and control subjects as markers of white matter integrity. We used both classical ROI-based statistics and whole-brain analysis techniques, including voxel-wise analysis with SPM5 and tract-based spatial statistics (TBSS). Using region of interest (ROI) analysis, we found increased MD bilaterally in the inferior cerebellar peduncles (ICP) and reduced FA in the right-sided ICP of ET patients. Whole-brain analyses with TBSS detected increased MD distributed in both motor and nonmotor white matter fibers of ET patients predominantly in the left parietal white matter, while there were no significant FA differences in these areas between ET patients and controls. Voxel-wise analysis with SPM detected significant increase of MD congruent with the highest probability of difference as detected by TBSS. VBM analysis of T1 images did not detect significant differences in either gray or white matter density between our study groups. In summary, we found evidence for changes in white matter MRI properties in ET. The circumscript pathology of the ICP corroborates the pathogenetic concept of the cerebellum and its projections as key structures for tremor generation in ET. Moreover, increased diffusivity in white matter structures of both hemispheres suggests widespread alterations of fiber integrity in motor and nonmotor networks in ET patients. The underlying cause of the DTI changes observed remains to be elucidated. PMID- 20572210 TI - Impact of exposure to pro-eating disorder websites on eating behaviour in college women. AB - OBJECTIVE: To assess whether exposure to pro-eating disorder (pro-ED) websites influences college women's eating behaviours. METHOD: Female college students with a body mass index (BMI) higher than 18 and no history of an ED were exposed to either pro-ED websites, healthy/exercise websites or tourist websites for 1.5 hours and were given quantitative and qualitative measures designed to assess changes in eating behaviour. RESULTS: The pro-ED website group experienced a significant one-week decrease in caloric intake from pre- to post-exposure (12,167 calories vs. 9697 calories). Following exposure, participants reported using techniques on the websites to aid with food reduction and had strong emotional reactions to the websites. These changes persisted for 3 weeks following the study's end. DISCUSSION: Even modest exposure to pro-ED websites may encourage significant changes in caloric intake and increased disordered eating behaviours. By extension, even greater exposures to these websites by at risk females may contribute to the development of EDs. PMID- 20572211 TI - NMR-based detection of acetylation sites in peptides. AB - Acetylation of histone tails as well as non-histone proteins was found to be a major component of the 'chromatin code' that regulates transcription through the recruitment of transcription factors, co-regulators and DNA-binding proteins. Acetylation can have several effects modifying protein-protein interactions, protein activity, localization and stability. Using NMR spectroscopy, we provide a simple way to detect acetyl moieties at the epsilon-amino function of lysine residues based on peptides derived from Histone H4 and TDG amino-terminal domains. Significant changes of acetyl-lysine resonances as compared to non acetylated residues allow a direct identification of specific acetylated lysine. We also show that, in unfolded peptides, acetylation of lysine side chains leads to characteristic NMR signals that vary only weakly depending on the primary sequence or the total number of acetylated sites, indicating that the acetamide group does not establish any interactions with other residues. Furthermore, resonance changes upon acetylation are restricted to residues nearby the acetylation site, indicating that acetylation does not modify the overall peptide conformation. PMID- 20572212 TI - Structures of DNA polymerases caught processing size-augmented nucleotide probes. PMID- 20572213 TI - Single-molecule kinetics of two-step divalent cation chelation. PMID- 20572214 TI - Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. AB - Microdroplets in microfluidics offer a great number of opportunities in chemical and biological research. They provide a compartment in which species or reactions can be isolated, they are monodisperse and therefore suitable for quantitative studies, they offer the possibility to work with extremely small volumes, single cells, or single molecules, and are suitable for high-throughput experiments. The aim of this Review is to show the importance of these features in enabling new experiments in biology and chemistry. The recent advances in device fabrication are highlighted as are the remaining technological challenges. Examples are presented to show how compartmentalization, monodispersity, single-molecule sensitivity, and high throughput have been exploited in experiments that would have been extremely difficult outside the microfluidics platform. PMID- 20572215 TI - Ab initio thermochemistry of solid-state materials. AB - In this contribution we introduce an electronic-structure-theory-based approach to a quantum-chemical thermochemistry of solids. We first deal with local and collective atomic displacements and explain how to calculate these. The fundamental importance of the phonons, their dispersion relations, their experimental determination as well as their calculation is elucidated, followed by the systematic construction of the thermodynamic potentials on this basis. Subsequently, we provide an introduction for practical computation as well as a critical analysis of the level of accuracy obtainable. We then show how different solid-state chemistry problems can be solved using this approach. Among these are the calculation of activation energies in perovskite-like oxides, but we also consider the use of theoretical vibrational frequencies for determining crystal structures. The pressure and temperature polymorphism of elemental tin which has often been classically described is also treated, and we energetically classify the metastable oxynitrides of tantalum. We also demonstrate, using the case of high-temperature superconductors, that such calculations may be used for an independent evaluation of thermochemical data of unsatisfactory accuracy. Finally, we show the present limits and the future challenges of the theory. PMID- 20572216 TI - Homogeneous gold catalysis beyond assumptions and proposals--characterized intermediates. AB - Gold catalysis is a very active area in the field of catalysis research. New reactions are published every week, amazing changes in the connectivity are often observed, the number of applications in total synthesis is increasing...--but what are the mechanisms of these reactions? Sound information can be provided by knowledge about the intermediates of these reactions. PMID- 20572217 TI - Shape-persistent organic cage compounds by dynamic covalent bond formation. AB - One area of supramolecular chemistry involves the synthesis of discrete three dimensional molecules or supramolecular aggregates through the coordination of metals. This field also concerns the chemistry of supramolecular cage compounds constructed through the use of such coordination bonds. To date, there exists a broad variety of supramolecular cage compounds; however, analogous organic cage compounds formed with only covalent bonds are relatively rare. Recent progress in this field can be attributed to important advances, not least the application of dynamic covalent chemistry. This concept makes it possible to start from readily available precursors, and in general allows the synthesis of cage compounds in fewer steps and usually higher yields. PMID- 20572218 TI - Reaction of singlet dioxygen with phosphine-borane derivatives: from transient phosphine peroxides to crystalline peroxoboronates. PMID- 20572219 TI - A water soluble donor-acceptor [2]catenane that can switch between a coplanar and a Gemini-sign conformation. PMID- 20572220 TI - Real-space observation of surface termination of a complex metal oxide catalyst. PMID- 20572221 TI - Bandgap-like strong fluorescence in functionalized carbon nanoparticles. PMID- 20572222 TI - Coordinatively immobilized monolayers on porous coordination polymer crystals. PMID- 20572223 TI - Metal-free catalytic boration at the beta-position of alpha,beta-unsaturated compounds: a challenging asymmetric induction. PMID- 20572224 TI - Enzymatic site-specific functionalization of protein methyltransferase substrates with alkynes for click labeling. PMID- 20572226 TI - A docosanuclear {Mo8Mn14} cluster based on [Mo(CN)7]4-. PMID- 20572225 TI - Decoding the logic of the tRNA regiospecificity of nonribosomal FemX(Wv) aminoacyl transferase. PMID- 20572227 TI - Halogen bond anion templated assembly of an imidazolium pseudorotaxane. PMID- 20572228 TI - High-throughput method for determining the enantioselectivity of enzyme-catalyzed hydroxylations based on mass spectrometry. PMID- 20572229 TI - Convergence leads to success: total synthesis of the complex nonribosomal peptide polytheonamide B. PMID- 20572230 TI - Catalytic activity enhancement for oxygen reduction on epitaxial perovskite thin films for solid-oxide fuel cells. PMID- 20572231 TI - Vitamin B12 mimics having a peptide backbone and tuneable coordination and redox properties. PMID- 20572234 TI - Palladium-catalyzed coupling reactions: carbonylative Heck reactions to give chalcones. PMID- 20572235 TI - Highly efficient and site-selective phosphane modification of proteins through hydrazone linkage: development of artificial metalloenzymes. PMID- 20572232 TI - An artificial metalloenzyme: creation of a designed copper binding site in a thermostable protein. PMID- 20572236 TI - Reversible three-state switching of multicolor fluorescence emission by multiple stimuli modulated FRET processes within thermoresponsive polymeric micelles. PMID- 20572237 TI - Total syntheses of dalesconol A and B. PMID- 20572238 TI - Conformational switching of G-quadruplex DNA by photoregulation. PMID- 20572239 TI - Water chains in hydrophobic crystal channels: nanoporous materials as supramolecular analogues of carbon nanotubes. PMID- 20572240 TI - Alpha-oligofurans: molecules without a twist. PMID- 20572248 TI - Determination of carbohydrate-binding preferences of human galectins with carbohydrate microarrays. AB - Galectins are a class of carbohydrate-binding proteins named for their galactose binding preference and are involved in a host of processes ranging from homeostasis of organisms to immune responses. As a first step towards correlating the carbohydrate-binding preferences of the different galectins with their biological functions, we determined carbohydrate recognition fine-specificities of galectins with the aid of carbohydrate microarrays. A focused set of oligosaccharides considered relevant to galectins was prepared by chemical synthesis. Structure-activity relationships for galectin-sugar interactions were determined, and these helped in the establishment of redundant and specific galectin actions by comparison of binding preferences. Distinct glycosylations on the basic lactosyl motifs proved to be key to galectin binding regulation--and therefore galectin action--as either high-affinity ligands are produced or binding is blocked. High-affinity ligands such as the blood group antigens that presumably mediate particular functions were identified. PMID- 20572249 TI - Streptococcus mutans inhibits Candida albicans hyphal formation by the fatty acid signaling molecule trans-2-decenoic acid (SDSF). AB - In the human mouth, fungi and several hundred species of bacteria coexist. Here we report a case of interkingdom signaling in the oral cavity: A compound excreted by the caries bacterium Streptococcus mutans inhibits the morphological transition from yeast to hyphae, an important virulence trait, in the opportunistic fungus Candida albicans. The compound excreted by S. mutans was originally studied because it inhibited signaling by the universal bacterial signal autoinducer-2 (AI-2), determined by the luminescence of a Vibrio harveyi sensor strain. The inhibitor was purified from cell-free culture supernatants of S. mutans guided by its activity. Its chemical structure was elucidated by using NMR spectroscopy and GC-MS and proved to be trans-2-decenoic acid. We show that trans-2-decenoic acid does not inhibit AI-2-specific signaling, but rather the luciferase reaction used for its detection. A potential biological role of trans 2-decenoic acid was then discovered. It is able to suppress the transition from yeast to hyphal morphology in the opportunistic human pathogen Candida albicans at concentrations that do not affect growth. The expression of HWP1, a hyphal specific signature gene of C. albicans, is abolished by trans-2-decenoic acid. trans-2-Decenoic acid is structurally similar to the diffusible signal factor (DSF) family of interkingdom-signaling molecules and is the first member of this family from a Gram-positive organism (Streptococcus DSF, SDSF). SDSF activity was also found in S. mitis, S. oralis, and S. sanguinis, but not in other oral bacteria. SDSF could be relevant in shaping multispecies Candida bacteria biofilms in the human body. PMID- 20572250 TI - Protocols for the sequential solid-state NMR spectroscopic assignment of a uniformly labeled 25 kDa protein: HET-s(1-227). AB - The sequence-specific resonance assignment of a protein forms the basis for studies of molecular structure and dynamics, as well as to functional assay studies by NMR spectroscopy. Here we present a protocol for the sequential 13C and 15N resonance assignment of uniformly [15N,13C]-labeled proteins, based on a suite of complementary three-dimensional solid-state NMR spectroscopy experiments. It is directed towards the application to proteins with more than about 100 amino acid residues. The assignments rely on a walk along the backbone by using a combination of three experiments that correlate nitrogen and carbon spins, including the well-dispersed Cbeta resonances. Supplementary spectra that correlate further side-chain resonances can be important for identifying the amino acid type, and greatly assist the assignment process. We demonstrate the application of this assignment protocol for a crystalline preparation of the N terminal globular domain of the HET-s prion, a 227-residue protein. PMID- 20572251 TI - An RNA aptamer that selectively inhibits the enzymatic activity of protein tyrosine phosphatase 1B in vitro. AB - SELEX was used to create an RNA aptamer targeted to protein tyrosine phosphatase 1B (PTP1B), an enzyme implicated in type 2 diabetes, breast cancer and obesity. We found an aptamer that strongly inhibits PTP1B in vitro with a Ki of less than 600 pM. This slow-binding, high-affinity inhibitor is also highly selective, with no detectable effect on most other tested phosphatases and approximately 300:1 selectivity over the closely related TC-PTP. Through controlled synthesis of truncated variants of the aptamer, we isolated shorter forms that inhibit PTP1B. We also investigated various single-nucleotide modifications to probe their effects on the aptamer's secondary structure and inhibition properties. This family of aptamers represents an exciting option for the development of lead nucleotide-based compounds in combating several human cancers and metabolic diseases. PMID- 20572252 TI - Two-headed PROTAC: an effective new tool for targeted protein degradation. PMID- 20572254 TI - Comparison of trap-state distribution and carrier transport in nanotubular and nanoparticulate TiO(2) electrodes for dye-sensitized solar cells. AB - Dye-sensitized solar cells (DSCs) with nanotubular TiO(2) electrodes of varying thicknesses are compared to DSCs based on conventional nanoparticulate electrodes. Despite the higher degree of order in one-dimensional nanotubular electrodes, electron transport times and diffusion coefficients, determined under short-circuit conditions, are comparable to those of nanoparticulate electrodes. The quasi-Fermi level, however, is much lower in the nanotubes, suggesting a lower concentration of conduction band electrons. This provides evidence for a much higher diffusion coefficient for conduction band electrons in nanotubes than in nanoparticulate films. The electron lifetime and the diffusion length are significantly longer in nanotubular TiO(2) electrodes than in nanoparticulate films. Nanotubular electrodes have a trap distribution that differs significantly from nanoparticulate electrodes; they possess relatively deeper traps and have a characteristic energy of the exponential distribution that is more than two times that of nanoparticulate electrodes. PMID- 20572253 TI - Parallel incorporation of different fluorinated amino acids: on the way to "teflon" proteins. PMID- 20572255 TI - Local disorder in hydrogen storage compounds: the case of lithium amide/imide. AB - Amides and imides of alkali metals are a very promising class of materials for use as a hydrogen-storage system, as they are able to store and release hydrogen via a chemical route at controllable temperatures and pressures. We critically revise the present picture of the atomic structure of the lightest member (LiNH(2)/Li(2)NH) by using a combined computational and experimental approach. Specifically, ab initio path integral molecular dynamics simulations and solid state (1)H NMR techniques are combined. The results show that the presently assumed local structure might be inconsistent or at least incomplete and needs considerable revision. In particular, the Li atoms turn out to be more mobile and more disordered than suggested by structural data obtained from X-ray scattering. Also, the configuration of the hydrogen atoms, which is accessible via the NMR experiment and the corresponding first-principles calculations, is different from the previously assumed data. The computed and experimentally observed (1)H NMR parameters are in very good mutual agreement and illustrate the unusual chemical environment of the hydrogen atoms in this system. Incorporating our results on the new lithium data, we show that the effect of nuclear quantum delocalization for the hydrogen atoms is considerably reduced compared to the perfect crystal structure. PMID- 20572256 TI - Flexible magnetic nanoparticles-reduced graphene oxide composite membranes formed by self-assembly in solution. AB - A facile and robust route for the pre-synthesized Fe(3)O(4) nanoparticles (NPs) exclusively assembled on both sides of reduced graphene oxide (RGO) sheets with tunable density forming two-dimensional NPs composite membranes is developed in solution. The assembly is driven by electrostatic attraction, and the nanocomposite sheets display considerable mechanical robustness, such as it can sustain supersonic and solvothermal treatments without NPs falling off, also, can freely float in solution and curl into a tube. The obtained two-dimensional composite grain membranes exhibit superparamagnetic behavior at room temperature but responds astutely to an external magnetic field. In addition, these magnetic composite membranes show an enhanced absorption capability for microwaves. The grain sheets are attractive for biomedical, sensors, environmental applications and electric-magnetic devices benefited from large surfaces, high magnetization moment, and superparamagnetic properties. The effective integration of oxide nanocrystals on RGO sheets provides a new way to design semiconductor-carbon nanocomposites for nanodevices or catalytic applications. PMID- 20572257 TI - UV-dissipation mechanisms in the eumelanin building block DHICA. AB - The UV-dissipative mechanisms of the eumelanin building block 5,6-dihydroxyindole 2-carboxylic acid (DHICA) and the 4,7-dideutero derivative (DHICA-d(2)) in buffered H(2)O or D(2)O have been characterized by using ultrafast time-resolved fluorescence spectroscopy. Excitation of the carboxylate anion form, the dominating state at neutral pH, leads to dual fluorescence. The band peaking at lambda=378 nm is caused by emission from the excited initial geometry. The second band around lambda=450 nm is owed to a complex formed between the mono-anion and specific buffer components. In the absence of complex formation, the mono-anion solely decays non-radiatively or by emission with a lifetime of about 2.1 ns. Excitation of the neutral carboxylic acid state, which dominates at acidic pH, leads to a weak emission around lambda=427 nm with a short lifetime of 240 ps. This emission originates from the zwitterionic state, formed upon excitation of the neutral state by sub-ps excited-state intramolecular proton transfer (ESIPT) between the carboxylic acid group and the indole nitrogen. Future studies will unravel whether this also occurs in larger building blocks and ESIPT is a built in photoprotective mechanism in epidermal eumelanin. PMID- 20572258 TI - Hydrogen loading of oxide powder particles: a transmission IR study for the case of zinc oxide. PMID- 20572260 TI - A method for obtaining randomized block designs in preclinical studies with multiple quantitative blocking variables. AB - A method is proposed for block randomization of treatments to experimental units that can accommodate both multiple quantitative blocking variables and unbalanced designs. Hierarchical clustering in conjunction with leaf-order optimization is used to block experimental units in multivariate space. The method is illustrated in the context of a diabetic mouse assay. A simulation study is presented to explore the utility of the proposed randomization method relative to that of a completely randomized approach, both in the presence and absence of covariate adjustment. An example R function is provided to illustrate the implementation of the method. PMID- 20572261 TI - Fabrication of patterned polymer brushes on chemically active surfaces by in situ hydrogen-bond-mediated attachment of an initiator. PMID- 20572259 TI - Focal adhesion kinase is essential for cardiac looping and multichamber heart formation. AB - Focal adhesion kinase (FAK) is a critical mediator of matrix- and growth factor induced signaling during development. Myocyte-restricted FAK deletion in mid gestation mice results in impaired ventricular septation and cardiac compaction. However, whether FAK regulates early cardiogenic steps remains unknown. To explore a role for FAK in multi-chambered heart formation, we utilized anti-sense morpholinos to deplete FAK in Xenopus laevis. Xenopus FAK morphants exhibited impaired cardiogenesis, pronounced pericardial edema, and lethality by tadpole stages. Spatial-temporal assessment of cardiac marker gene expression revealed that FAK was not necessary for midline migration, differentiation, fusion of cardiac precursors, or linear heart tube formation. However, myocyte proliferation was significantly reduced in FAK morphant heart tubes and these tubes failed to undergo proper looping morphogenesis. Collectively our data imply that FAK plays an essential role in chamber outgrowth and looping morphogenesis likely stimulated by fibroblast growth factors (and possibly other) cardiotrophic factors. PMID- 20572262 TI - Fast analysis of phenolic acids by electrokinetic supercharging-nonaqueous capillary electrophoresis. AB - A method was developed to analyze phenolic acids by nonaqueous CE after online concentration with electrokinetic supercharging. The EOF was reversed using a polyelectrolyte multilayer approach based on the successive adsorption of poly(diallyldimethylamonium chloride) and poly(styrenesulfonate) to reduce the analysis time. The results showed that the coatings were stable during 40 consecutive injections. Four phenolic acids were separated within 8 min using 30 mM ammonium acetate (pH* 8.0). The electrokinetic injection time and terminator length of the electrokinetic supercharging method were optimized to improve the detection sensitivity. Under the optimized conditions (electrokinetic injection of 100 s, -10 kV; terminator of 20 mM 2-(cyclohexylamino) ethanesulfonic acid, 22 s, 0.5 psi), the sensitivity was enhanced from 300- to 440-fold. The detection limits, based on three times noise, were in the range 1.0-2.5 ng/mL. PMID- 20572263 TI - Modeling solvation on the chemically modified silica surfaces. AB - A detailed molecular-level description of the retention mechanism in RP-HPLC is a point of great interest to analytical chemists. For this purpose, the solvent adsorption on the octadecyl stationary-bonded phase was investigated. Preferential adsorption of solvents from the acetonitrile-water mobile phase was modeled on the silica surface with one, two, three and four organic ligands, which represents a series of non-end-capped-bonded phases with different coverage density of bonded ligands. As a result of the computer simulation, the increase of adsorbed acetonitrile around bonded ligands is observed. The number of water molecules near the modeled surface is observed as well. The results are in agreement with experimental measurement of acetonitrile excess adsorption isotherms on the series of in-house made stationary-bonded phase. PMID- 20572264 TI - Determination of ergot alkaloids from grains with UPLC-MS/MS. AB - A simple and rapid method for determining six ergot alkaloids and four of their respective epimers was developed for rye and wheat. The analytes were extracted from the sample matrix with ACN/ammonium carbonate solution. The extract was purified with a commercial push-through SPE column (Mycosep 150 Ergot). After concentration and filtration steps, the final separation of the analytes was achieved with ultra-performance LC-MS/MS. The chromatographic separation of the ergot alkaloids was achieved in 4.5 min. The method performance proved satisfactory in the preliminary validation. The calculated LOQs were low ranging from 0.01 to 1.0 microg/kg for wheat and from 0.01 to 10.0 microg/kg for rye. At the concentration levels of 10, 50 and 200 microg/kg, the recoveries were between 80 and 120% in most cases and the within-day repeatability (expressed as RSD) ranged between 1.3 and 13.9%. Despite the cleanup of the samples, some matrix effect was observed in the MS, highlighting the necessity of using matrix assisted standards. This is the first article to describe the application of the push-through columns and ultra-performance LC in the analysis of ergot alkaloids. PMID- 20572265 TI - Nano and rapid resolution liquid chromatography-electrospray ionization-time of flight mass spectrometry to identify and quantify phenolic compounds in olive oil. AB - The applicability of nanoLC-ESI-TOF MS for the analysis of phenolic compounds in olive oil was studied and compared with a HPLC method. After the injection, the compounds were focused on a short capillary trapping column (100 microm id, effective length 20 mm, 5 microm particle size) and then nanoLC analysis was carried out in a fused silica capillary column (75 microm id, effective length 10 microm, 3 microm particle size) packed with C18 stationary phase. The mobile phase was a mixture of water + 0.5% acetic acid and ACN eluting at 300 nL/min in a gradient mode. Phenolic compounds from different families were identified and quantified. The quality parameters of the nanoLC method (linearity, LODs and LOQs, repeatability) were evaluated and compared with those obtained with HPLC. The new methodology presents better sensitivity (reaching LOD values below 1 ppb) with less consumption of mobile phases, but worse repeatability, especially inter day repeatability, resulting in more difficulties to get highly accurate quantification. The results described in this article open up the application fields of this technique to cover a larger variety of compounds and its advantages will make it especially useful for the analysis of samples containing low concentration of phenolic compounds, as for instance, in biological samples. PMID- 20572267 TI - Synthesis and evaluation of silica hydride-based fluorinated stationary phases. AB - Two novel silica hydride-based fluorinated bonded phases have been synthesized using a hydrosilation procedure to test combined fluorine and hydride selectivity. The bonded moieties were characterized by elemental and spectral analysis. Chromatographic testing was done using hydrophilic analytes in the aqueous normal phase mode. At higher amounts of the nonpolar solvent in the mobile phase, there should be increased retention for solutes such as acids, bases and other polar compounds, whereas nonpolar solutes can be retained when water is increased as in RP chromatography. The synergistic effects of the fluorinated phase selectivity and aqueous normal phase retention on a hydride surface have been explored for small polar molecules. The stability and repeatability of the hydride-based fluorinated stationary phases were evaluated. The use of acetone as the organic component in the mobile phase was also tested. PMID- 20572266 TI - Pressurized liquid extraction and GC-MS analysis for simultaneous determination of seven components in Cinnamomum cassia and the effect of sample preparation. AB - A pressurized liquid extraction and GC-MS method was developed for simultaneous quantitative determination of the seven components, including cinnamaldehyde, copaene, cinnamic acid, coumarin, 2-methoxycinnamaldehyde, 2-methoxycinnamic acid and safrole in Cinnamomum cassia. The results showed that methanol and ethanol was not available for extraction of cinnamaldehyde and 2-methoxycinnamaldehyde due to aldol reaction. The developed method was validated to be sensitive, accurate and simple, and was successfully employed for the analysis of 15 samples of C. cassia. The contents of the investigated components were significantly variant and cinnamaldehyde is the most abundant compound, but safrole was not detected in all samples. PMID- 20572268 TI - A simple method for cell sheet fabrication using mica surfaces grafted with peptide detergent A(6)K. AB - Cell sheet technology is a very important strategy for scaffold-free tissue engineering. In order to fabricate cell sheets by a simple method, peptide detergent A(6)K was grafted on mica surfaces by dropping its aqueous solution at different concentrations on the surface. As revealed by surface topographical observation and water contact angle measurement, the most hydrophobic surface was obtained using peptide solution at the concentration of 0.2 mg . mL(-1). The peptide-grafted mica surface was used to culture mouse preosteoblast cell MC3T3 E1. After the cells reached confluence and the peptide was biodegraded, an intact cell sheet was peeled from the mica. This simple method does not need any non biological reagents or complicated procedures, and may have great potential in tissue engineering based on cell sheet technology. PMID- 20572269 TI - Protein adsorption on a glycosylated polyacrylonitrile surface: monitoring with QCM and SPR. AB - A simple and efficient method to fabricate a glycosylated surface on a polyacrylonitrile-based film is described. Construction and protein adsorption processes were monitored in situ using a QCM. A PANCHEMA film was deposited on the gold surface of the quartz crystal, and the glycosylated surface was then constructed through surface modification. Con A and BSA were used as probes to study the specificity of this surface to proteins. It can recognize Con A, while showing no specific interaction with BSA. The binding affinity indicates the presence of strong multivalent interactions between Con A and the glucose residues (cluster glycoside effect). Reproducibility and repeatability of the glycosylated polymer surface are sufficient to allow specific adsorption of Con A. PMID- 20572270 TI - Microparticles for drug delivery based on functional polycaprolactones with enhanced degradability: loading of hydrophilic and hydrophobic active compounds. AB - Microparticle drug carriers made of biodegradable functional polyesters were produced. The polyesters consist of a poly(epsilon-caprolactone) backbone bearing pendant acryloyloxy and methacryloyloxy groups. Stable microparticles were prepared via an oil/water emulsion-solvent evaporation technique eventually combined with a simultaneous crosslinking procedure. Crosslinked particles were obtained via photo-crosslinking and Michael type addition using diamines as crosslinking agents. Encapsulation of a hydrophobic fluorescent dye and a hydrophilic protein, as model drugs, were performed and confirmed by optical microscopy and Raman spectroscopy. The presence of the functional groups allow for not only the tuning of the degradation rate, but also for further processing and (bio)functionalization. PMID- 20572271 TI - Biodegradable and electroactive TEMPO-substituted acrylamide/lactide copolymers. AB - Copolymers composed of PLA and PTAm were prepared by a macromonomer approach. The PLA bearing vinyl group at chain end was copolymerized with 2,2,6,6 tetrametylpiperidine-4-ylacrylamide. The resulted copolymers were oxidized by a peroxide to give PTAm-g-PLA. The structures of the copolymers were confirmed by NMR and FTIR spectroscopy. The comparison of (1)H NMR results and SQUID measurements demonstrated that the oxidation of the PTAm fragment proceeded almost to completion. An MTT assay, cell adhesion and spreading evaluation showed that the copolymers exhibited improved cytocompatibility as compared to the PTAm homopolymer due to the introduction of the biocompatible PLA moiety. PMID- 20572272 TI - Polycation structure mediates expression of lyophilized polycation/pDNA complexes. AB - Lyophilization of polycation/pDNA complexes provides stable, long-term storage of complexes prior to clinical use but also reduces gene delivery efficiency. We examined whether polycation structure mediates effects of lyophilization on gene expression. Linear and branched PEI of the same molecular weight were used as a model system. Interestingly, pDNA/linear PEI complexes led to much smaller effects on gene expression following lyophilization compared with branched PEI complexes. The effect of polycation structure correlated with changes in dissociation ability of pDNA/PEI complexes. These results will be useful for developing new gene delivery vehicles. PMID- 20572273 TI - James Michael Creeth, 1924-2010. PMID- 20572274 TI - Poly(beta-cyclodextrin)/curcumin self-assembly: a novel approach to improve curcumin delivery and its therapeutic efficacy in prostate cancer cells. AB - A novel PCD/CUR self-assembly approach for improved curcumin delivery to prostate cancer cells is described. The formation of PCD/CUR was confirmed using FTIR, DSC, TGA, and SEM/TEM, and their stability and solubility under physiological conditions was demonstrated. A mechanism for self-assembly is proposed. Intracellular uptake of the self-assemblies was studied by flow cytometry and immunofluorescence microscopy. The therapeutic efficacy was determined by cell proliferation and colony formation assays using C4-2, DU145 and PC3 prostate cancer cells. The results suggest that the PCD/CUR formulation could be a useful system for improving curcumin delivery and its therapeutic efficacy in prostate cancer. PMID- 20572275 TI - The softer and more hydrophobic the better: influence of the side chain of polymethacrylate nanoparticles for cellular uptake. AB - Intracellular uptake of nanoparticles is highly interesting for labeling of cells, drug delivery, or non-viral gene delivery. In this study we have synthesized a wide variety of poly(alkyl methacrylate) nanoparticles with the same size and investigated their uptake into cells. The nanoparticles were prepared from alkylmethacrylates with different linear and branched ester chains as well as from benzylmethacrylate using the miniemulsion polymerizaiton technique. By adding a fluorescent dye as a marker, the internalization of the nanoparticles could be investigated quantitatively with flow cytometry and qualitatively with confocal laser scanning microscopy. With increasing side chain of the ester and therefore increasing hydrophobicity and at glass transition temperature (T(g)), below the incubation temperature of 37 degrees C the uptake of the nanoparticles into cells is favored. PMID- 20572276 TI - Bioresorbable electrospun fibers for immobilization of thiol-containing compounds. AB - For the reconstruction of functional tissue, biodegradable scaffolds providing specific surface functionality and a three-dimensional structure matching that of the damaged tissue are needed. Fibers capable of controlling cell-fiber interaction were produced by electrospinning of PDLLA-block-PEG with thiol reactive end groups from a solvent mixture. The hydrophilic fibers uniquely combine minimized non-specific protein adsorption and well-defined surface reactivity allowing controlled immobilization of peptides and proteins. Human dermal fibroblasts show adherence and proliferation on the surface of RGDC functionalized electrospun PDLLA-block-PEG fibers. PMID- 20572277 TI - Analytical ultracentrifugation. PMID- 20572278 TI - Enhancement of glutaryl-7-aminocephalosporanic acid acylase activity of gamma glutamyltranspeptidase of Bacillus subtilis. AB - Semisynthetic cephalosporins, the best-selling antibiotics worldwide, are derived from 7-aminocephalosporanic acid (7-ACA). Currently, in the pharmaceutical industrie, 7-ACA is mainly produced from cephalosporin C by sequential application of D-amino acid oxidase and cephalosporin acylase. Here we study the potential of industrially amenable enzyme gamma-glutamyltranspeptidase from Bacillus subtilis for 7-ACA production, since the wild-type gamma glutamyltranspeptidase of B. subtilis has inherent glutaryl-7 aminocephalosporanic acid acylase activity with a k(cat) value of 0.0485 s(-1). Its activity has been enhanced by site directed and random mutagenesis. The k(cat)/K(m) value was increased to 3.41 s(-1) mM(-1) for a E423Y/E442Q/D445N mutant enzyme and the kcat value was increased to 0.508 s(-1) for a D445G mutant enzyme. Consequently, the catalytic efficiency and the turnover rate were improved up to about 1000-fold and 10-fold, compared with the wildtype gamma glutamyltranspeptidase of B. subtilis. PMID- 20572279 TI - Automated lab-scale production of PVA/PEG-enzyme immobilisates. AB - Entrapment of biocatalysts by cryogelation is a gentle method to extend the scope of biocatalysis. To foster the use of this versatile method we devised an automated injector for the production of PVA/PEG beads. The device consists of a thermostated reservoir connected to a programmable injector nozzle and an agitated receiving bath for the droplets. This lab-scale production unit yields up to 1500 beads with immobilized enzyme per minute with a narrow size distribution and good roundness. PMID- 20572280 TI - Cell-selective, apoptosis-inducing rhodium(III) crown thiaether complexes. AB - Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF-7 and HT-29 and immortalized HEK-293 cells indicate that the dicationic kappa(2)N(imino) complexes [([9]aneS(3))RhCl(pp)](2+) are much more active than monocationic complexes [([9]aneS(3))RhCl(2)(L)](+) (L=imidazole, CH(3)CN). Whereas the kappa(2)N(amino) complex [([9]aneS(3))RhCl(piperazine)](2+) is inactive, replacing piperazine with the structurally analogous kappa(2)S (thiaether) ligand 1,4-dithiane restores cytotoxicity as evidenced by IC(50) values in the range 8.1-11.6 microM. Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC(50) values: 4.7-8.9 microM) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC(50) values: 0.6-1.9 microM) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7. A comparative annexin V-propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells. PMID- 20572281 TI - Synthesis and biological characterization of amidopropenyl hydroxamates as HDAC inhibitors. AB - A series of amidopropenyl hydroxamic acid derivatives were prepared as novel inhibitors of human histone deacetylases (HDACs). Several compounds showed potency at <100 nM in the HDAC inhibition assays, sub-micromolar IC(50) values in tests against three tumor cell lines, and remarkable stability in human and mouse microsomes was observed. Three representative compounds were selected for further characterization and submitted to a selectivity profile against a series of class I and class II HDACs as well as to preliminary in vivo pharmacokinetic (PK) experiments. Despite their high microsomal stability, the compounds showed medium to-high clearance rates in in vivo PK studies as well as in rat and human hepatocytes, indicating that a major metabolic pathway is catalyzed by non microsomal enzymes. PMID- 20572282 TI - Rapid and slow generation of 1-trifluoromethylvinyllithium: syntheses and applications of CF3-containing allylic alcohols, allylic amines, and vinyl ketones. AB - 1-(Trifluoromethyl)vinylation is accomplished in two protocols by the in situ generation of thermally unstable 3,3,3-trifluoroprop-1-en-2-yllithium (1): 1) a rapid lithium-halogen-exchange reaction of 2-bromo-3,3,3-trifluoroprop-1-ene (2) takes effect with sec-BuLi at -105 degrees C to generate vinyllithium 1, which reacts with more reactive electrophiles, such as aldehydes and N-tosylimines before its decomposition, to afford 2-(trifluoromethyl)allyl alcohols and N-[2 (trifluoromethyl)allyl] sulfoamides in good yield; 2) treatment of 2 with nBuLi at -100 degrees C causes a slow lithium-halogen exchange of 2, which gives rise to a mixture of 1 and nBuLi. Vinyllithium 1 is preferentially trapped with less reactive electrophiles, such as N,N-dimethylamides in the presence of BF(3)OEt(2), to afford 1-(trifluoromethyl)vinyl ketones in good yield. Versatility of the products toward syntheses of CF(3)-containing ring-fused cyclopentenones is also demonstrated by the Pauson-Khand reaction and the Nazarov cyclization. PMID- 20572283 TI - Heterogeneous aromatic amination of aryl halides with arylamines in water with PS PEG resin-supported palladium complexes. AB - Catalytic aromatic amination is achieved in water under heterogeneous conditions by the use of immobilized palladium complexes coordinated with the amphiphilic polystyrene-poly(ethylene glycol) resin-supported di(tert-butyl)phosphine ligand. Aromatic amination of aryl halides with diphenylamine and N,N-double arylation of anilines with bromobenzene were found to proceed in water with broad substrate tolerance to give the triarylamines in high yield with high recyclability of the polymeric catalyst beads. Very little palladium leached from the polymeric catalyst under the water-based reaction conditions to provide a green and clean (metal-uncontaminated) protocol for the preparation of triarylamines, including the optoelectronically active N,N,N',N'-tetraaryl-1,1'-biphenyl-4,4'-diamines (TPDs). PMID- 20572285 TI - Towards Raman-based epidemiological typing of Pseudomonas aeruginosa. AB - Raman spectra of bacteria can be used as highly specific fingerprints, enabling discrimination at strain level. Pseudomonas aeruginosa strains can be strongly pigmented, making it difficult to obtain high quality spectra of such isolates due to high fluorescent spectral backgrounds. Furthermore, the spectra that could be measured with acceptable quality often showed large spectral variations limiting the reproducibility required for strain level discrimination. P. aeruginosa produces a characteristic yellowish green fluorescent pigment, called pyoverdin. Applying a washing procedure to reduce the amount of fluorescent pigment, enabled the highly pigmented isolates to be measured with sufficient spectral quality. Isolation of the pigment/pyoverdin spectral features, together with spectral scaling methods improved reproducibility. It will be important to analyze the range of the spectral variations that can occur and ensure the correction of all of these factors to obtain the highest reproducibility required for strain level typing. PMID- 20572286 TI - Interaction between noble metal nanoparticles and light for contaminant decomposition. PMID- 20572284 TI - Ultrasensitive label-free photothermal imaging, spectral identification, and quantification of cytochrome c in mitochondria, live cells, and solutions. AB - Light-absorbing endogenous cellular proteins, in particular cytochrome c, are used as intrinsic biomarkers for studies of cell biology and environment impacts. To sense cytochrome c against real biological backgrounds, we combined photothermal (PT) thermal-lens single-channel schematic in a back-synchronized measurement mode and a multiplex thermal-lens schematic in a transient high resolution (ca. 350 nm) imaging mode. These multifunctional PT techniques using continuous-wave (cw) Ar+ laser and a nanosecond pulsed optical parametric oscillator in the visible range demonstrated the capability for label-free spectral identification and quantification of trace amounts of cytochrome c in a single mitochondrion alone or within a single live cell. PT imaging data were verified in parallel by molecular targeting and fluorescent imaging of cellular cytochrome c. The detection limit of cytochrome c in a cw mode was 5 x 10(-9) mol/L (80 attomols in the signal-generation zone); that is ca. 103 lower than conventional absorption spectroscopy. Pulsed fast PT microscopy provided the detection limit for cytochrome c at the level of 13 zmol (13 x 10(-21) mol) in the ultrasmall irradiated volumes limited by optical diffraction effects. For the first time, we demonstrate a combination of high resolution PT imaging with PT spectral identification and ultrasensitive quantitative PT characterization of cytochrome c within individual mitochondria in single live cells. A potential of far-field PT microscopy to sub-zeptomol detection thresholds, resolution beyond diffraction limit, PT Raman spectroscopy, and 3D imaging are further highlighted. PMID- 20572287 TI - Self-sustainable production of hydrogen, chemicals, and energy from renewable alcohols by electrocatalysis. AB - The selective and simultaneous production of hydrogen and chemicals from renewable alcohols, such as ethanol, glycerol, and ethylene glycol, can be accomplished by means of electrolyzers in which the anode electrocatalyst is appropriately designed to promote the partial and selective oxidation of the alcohol. In the electrolyzers described herein, the production of 1 kg of hydrogen from aqueous ethanol occurs with one-third the amount of energy required by a traditional H(2)/O(2) electrolyzer, by virtue of the much lower oxidation potential of ethanol to acetate vs. water to oxygen in alkaline media (E(0)=0.10 V vs. 1.23 V). The self-sustainability of H(2) production is ensured by the simultaneous production of 25 kg of potassium acetate for every kg of H(2), if the promoting co-electrolyte is KOH. PMID- 20572288 TI - Effective gasoline production strategies by catalytic cracking of rapeseed vegetable oil in refinery conditions. PMID- 20572289 TI - Ammonia: an environmentally friendly nitrogen source for primary aniline synthesis. PMID- 20572291 TI - Fine needle aspiration of breast masses in HIV-infected patients: results from a large series. AB - BACKGROUND: There are limited studies investigating the cytopathology of HIV related breast disease. The aim of the current study was to evaluate a large series of fine needle aspirations (FNA) performed on breast lesions in HIV positive patients. METHODS: A retrospective review at the National Health Laboratory Service (NHLS) in Johannesburg, South Africa, was performed on confirmed HIV-positive patients who underwent breast FNA. Cases were evaluated for patient age and sex, presence of a clinical breast lesion, antiretroviral therapy use, specimen adequacy, and cytologic diagnosis. RESULTS: A total of 152 breast FNA procedures were recorded in patients of average age 36 years (range, 10-64 years). Cytologic findings in 100 females patients included 28 inadequate aspirates, 29 cases with a benign diagnosis, 25 abscesses, 3 with reactive intramammary lymphadenopathy, 3 with fat necrosis, 1 galactocele, 1 papillary lesion, 8 breast carcinomas, and 2 non-Hodgkin lymphomas. Fifty-two males underwent breast FNA, of which 6 were inadequate, and 43 (82.7%) showed gynecomastia. In 17 (40%) males with gynecomastia, a history of antiretroviral therapy was recorded. Two males were diagnosed with breast abscess and 1 with Kaposi sarcoma. Microbiology culture revealed 7 Mycobacterium tuberculosis infections in this patient population. CONCLUSIONS: FNA is a procedure to evaluate breast lesions and is capable of rendering results useful for a broad range of diagnoses likely to be encountered in an human immunodeficiency virus (HIV)-positive population. Unlike HIV-infected females who may present with a wide range of benign and neoplastic breast entities, HIV-positive males may have breast lesions that will most likely be attributed to gynecomastia associated with antiretroviral therapy. PMID- 20572292 TI - Utility of paired box gene 8 (PAX8) expression in fluid and fine-needle aspiration cytology: an immunohistochemical study of metastatic ovarian serous carcinoma. AB - BACKGROUND: Metastases from ovarian neoplasms are commonly encountered in peritoneal fluids. In addition, reactive mesothelial cells in effusion specimens can mimic ovarian serous carcinoma, making the diagnosis difficult. Calretinin has been recognized as a reliable immunohistochemical marker for mesothelial cells, whereas WT1 has proven useful in the diagnosis of ovarian serous carcinoma. This can present a diagnostic pitfall in effusion cytology, because mesothelial cells can demonstrate immunoreactivity for WT1. Recently, paired box gene 8 (PAX8) has been used in distinguishing ovarian from mammary carcinoma. To the authors' knowledge, no studies using PAX8 have been performed on peritoneal cytology specimens to date, and its expression in metastatic ovarian serous carcinoma has not been studied. METHODS: These markers, along with BerEP4 and MOC 31, were evaluated in cytology cell block preparations from 30 fluid cytology specimens and 11 fine-needle aspiration specimens. RESULTS: PAX8 was found to be positive in 37 of 41 (90%) ovarian carcinoma cases studied, and was a sensitive (90%) and specific (100%) marker for the detection of metastatic ovarian carcinoma. In addition, calretinin was found to be useful for identifying mesothelial cells in fluid cytology. Furthermore, although PAX8 and WT1 have demonstrated comparable sensitivity (90% and 93%, respectively) in diagnosing metastatic ovarian carcinoma, PAX8 appears to have superior specificity because staining is not observed in mesothelial cells. BerEP4 and MOC-31 were found to have a lower sensitivity and specificity compared with PAX8. CONCLUSIONS: PAX8 positive, calretinin-negative staining appears to be highly specific and sensitive for detecting metastatic ovarian serous carcinoma in cytologic preparations and can be useful in distinguishing it from mesothelial cells in fluid cytology. PMID- 20572293 TI - On the choice of the optimal periodic operation for a continuous fermentation process. AB - In this contribution we investigate the impact of the forcing waveform on the productivity of a continuous bioreactor governed by an unstructured, nonlinear kinetic model. The (periodic) forcing is applied on the substrate concentration in the feed. To this end, some alternative waveforms commonly encountered in practice are evaluated and their performance is compared. An analytical/numerical approach is used. The preliminary analytical step is based on the pi-criterion that gives useful information for small amplitudes. The extension to larger amplitudes, when significant improvements are expected, is then performed through a continuation-optimization procedure. It is found that the choice of the specific waveform has an impact on the performance of the process and there is no unique best forcing for any process condition, but its choice depends on the operating parameters and the forcing amplitude and frequency values. Further, the influence of the waveform functions on the wash-out conditions are extensively examined. The analysis shows that all the waveforms examined in this work may lead to significant enlargement of the nontrivial regime with respect to a steady state operation. In particular, square-wave forcing leads in practice to the extinction of the wash-out conditions for any feed substrate concentration and for a well defined choice of the forcing parameters. PMID- 20572294 TI - Radio frequency radiation causes no nonthermal damage in enzymes and living cells. AB - The ability of radio frequency radiation (RFR) to exert irreversible nonthermal (i.e., not caused by accompanying heat) effects on biologics has been widely debated due to a relative paucity of comprehensive critical details in published reports dealing with this issue. In this study, we used rigorous control over experimental conditions to determine whether continuous RFR nonthermally affects commercially important enzymes and live bacterial and human cells using three most commonly used frequencies in current RF identification technology, namely 2.45 GHz, 915 MHz, and 13.56 MHz. Diverse biological samples were exposed to RFR under deliberately harsh conditions to increase the likelihood of observing such effects should they exist. Enzymatic activities of horseradish peroxidase and beta-galactosidase in aqueous solution exhibited no statistically discernable consequences of even very intense RFR. Likewise, with putative thermal effects excluded, the viabilities of bacteria (both gram-positive and gram-negative) and of human cells were not detectably compromised by such an RFR exposure. PMID- 20572295 TI - LPS removal from an E. coli fermentation broth using aqueous two-phase micellar system. AB - In biotechnology, endotoxin (LPS) removal from recombinant proteins is a critical and challenging step in the preparation of injectable therapeutics, as endotoxin is a natural component of bacterial expression systems widely used to manufacture therapeutic proteins. The viability of large-scale industrial production of recombinant biomolecules of pharmaceutical interest significantly depends on the separation and purification techniques used. The aim of this work was to evaluate the use of aqueous two-phase micellar system (ATPMS) for endotoxin removal from preparations containing recombinant proteins of pharmaceutical interest, such as green fluorescent protein (GFPuv). Partition assays were carried out initially using pure LPS, and afterwards in the presence of E. coli cell lysate. The ATPMS technology proved to be effective in GFPuv recovery, preferentially into the micelle-poor phase (K(GFPuv) < 1.00), and LPS removal into the micelle-rich phase (%REM(LPS) > 98.00%). Therefore, this system can be exploited as the first step for purification in biotechnology processes for removal of higher LPS concentrations. PMID- 20572296 TI - Cryopreservation of human bone marrow-derived mesenchymal stem cells with reduced dimethylsulfoxide and well-defined freezing solutions. AB - The aim of this study is to investigate the feasibility of using well defined, serum-free freezing solutions with a reduced level of dimethylsulfoxide (DMSO) of 7.5, 5, and 2.5% (v/v) in the combination with polyethylene glycol (PEG) or trehalose to cryopreserve human bone marrow-derived mesenchymal stem cells (hBMSCs), a main source of stem cells for cell therapy and tissue engineering. The standard laboratory freezing protocol of around 1 degrees C/min was used in the experiments. The efficiency of 1,2-propandiol on cryopreservation of hBMSCs was explored. We measured the post-thawing cell viability and early apoptotic behaviors, cell metabolic activities, and growth dynamics. Cell morphology and osteogenic, adipogenic and chondrogenic differentiation capability were also tested after cryopreservation. The results showed that post-thawing viability of hBMSCs in 7.5% DMSO (v/v), 2.5% PEG (w/v), and 2% bovine serum albumin (BSA) (w/v) was comparable with that obtained in conventional 10% DMSO, that is, 82.9 +/- 4.3% and 82.7 +/- 3.7%, respectively. In addition, 5% DMSO (v/v) with 5% PEG (w/v) and 7.5% 1,2-propandiol (v/v) with 2.5% PEG (w/v) can provide good protection to hBMSCs when 2% albumin (w/v) is present. Enhanced cell viability was observed with the addition of albumin to all tested freezing solutions. PMID- 20572297 TI - Nanoporous protein matrix made of amyloid fibrils of beta2-microglobulin. AB - Amyloid fibrils are considered as novel nanomaterials because of their nanoscale width, a regular constituting structure of cross beta-sheet conformation, and considerable mechanical strength. By using an amyloidogenic protein of beta(2) microglobulin (beta(2)M) related to dialysis-related amyloidosis, nanoporous protein matrix has been prepared. The beta(2) M granules made of around 15 monomers showed an average size of 23.1 nm. They formed worm-like fibrils at pH 7.4 in 20 mM sodium phosphate containing 0.15 M NaCl following vigorous nondirectional shaking incubation, in which they became laterally associated and interwound to generate the porous amyloid fibrillar matrix with an average pore size of 30-50 nm. This nanoporous protein matrix was demonstrated to be selectively disintegrated by reducing agents, such as tris-(2-carboxyethyl) phosphine. High surface area with nanopores on the surface has been suggested to make the matrix of beta(2) M amyloid fibrils particularly suitable for applications in the area of nanobiotechnology including drug delivery and tissue engineering. PMID- 20572298 TI - Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. AB - Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuroendocrine tumors (NETs). In recent years, accumulating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carcinoid and pancreatic endocrine tumors. A phase III, randomized, placebo-controlled trial has now demonstrated that octreotide long acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to significantly lengthening time to tumor progression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti tumor therapies. PMID- 20572299 TI - Gastrointestinal involvement in systemic lupus erythematosus: insight into pathogenesis, diagnosis and treatment. AB - Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease characterized by the presence of a plethora of autoantibodies and immune complex formation. Virtually every system and organ can be affected by SLE. Gastrointestinal symptoms are common in SLE patients, and more than half of them are caused by adverse reactions to medications and viral or bacterial infections. Though not as common as lupus nephritis, SLE-related gastrointestinal involvement is clinically important because most cases can be life-threatening if not treated promptly. Lupus mesenteric vasculitis is the most common cause, followed by protein-losing enteropathy, intestinal pseudo-obstruction, acute pancreatitis and other rare complications such as celiac disease, inflammatory bowel diseases, etc. No specific autoantibody is identified as being associated with SLE-related gastroenteropathy. Imaging studies, particularly abdominal computed tomography scans, are helpful in diagnosing some SLE-related gastroenteropathies. Most of these complications have good therapeutic responses to corticosteroids and immunosuppressive agents. Supportive measures such as bowel rest, nutritional support, antibiotics and prokinetic medications are helpful in facilitating functional recovery and improving the outcome. PMID- 20572301 TI - Mesenteric lymph node cavitation syndrome. AB - The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal disease that fails to respond to a gluten-free diet. Splenic hypofunction may also be present. The cause is not known but its development during the clinical course of celiac disease is usually indicative of a poor prognosis for the intestinal disorder, a potential for significant complications including sepsis and malignancy, particularly T-cell lymphoma, and significant mortality. Modern abdominal imaging modalities may permit earlier detection in celiac disease so that earlier diagnosis and improved understanding of its pathogenesis may result. PMID- 20572300 TI - Small intestinal bacterial overgrowth syndrome. AB - Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID- 20572302 TI - Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis. AB - AIM: To investigate the effect of emodin on expression of claudin-4, claudin-5 and occludin, as well as the alveolar epithelial barrier in rats with pancreatitis induced by sodium taurocholate. METHODS: Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Emodin was injected via the external jugular vein 3 h after induction of acute pancreatitis. Rats from sham operation group and acute pancreatitis group were injected with normal saline (an equivalent volume as emodin) at the same time point. Samples of lung and serum were obtained 6 h after drug administration. Pulmonary morphology was examined with HE staining. Pulmonary edema was estimated by measuring water content in lung tissue samples. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) level were measured by enzyme-linked immunospecific assay. Serum amylase and pulmonary myeloperoxidase (MPO) activity were detected by spectrophotometry. Alveolar epithelial barrier was assessed by pulmonary dye extravasation. Expression of claudin-4, claudin-5 and occludin in lung tissue samples was examined by immunohistology, quantitative real-time reverse transcription polymerase chain reaction and Western blotting analysis, respectively. RESULTS: Pancreatitis associated lung injury was characterized by pulmonary edema, leukocyte infiltration, alveolar collapse, and elevated serum amylase level. The pulmonary damage, pulmonary pathological scores, serum amylase and MPO activity, TNF-alpha and IL-6 levels, and wet/dry ratio were decreased in rats after treatment with emodin. Immunostaining of claudin-4, claudin-5 and occludin was detected in lung tissue samples from rats in sham operation group, which was distributed in alveolar epithelium, vascular endothelium, and bronchial epithelium, respectively. The mRNA and protein expression levels of claudin-4, claudin-5 and occludin in lung tissue samples were markedly decreased, the expression level of claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin. CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis. PMID- 20572304 TI - Management of recto-vaginal fistulas after prosthetic reinforcement treatment for pelvic organ prolapse. AB - AIM: To communicate our findings on successful treatment of recto-vaginal fistulas (RVFs) after prosthetic reinforcement surgery of pelvic organ prolapse (POP). METHODS: A retrospective single center study between 1998 and 2008 was performed. A total of 80 patients with RVF were identified, of which five patients (6%), with a mean age of 65 years (range: 52-73), had undergone previous surgery for POP with prosthetic reinforcement. RESULTS: All patients complained about ongoing vaginal infections and febrile episodes. These symptoms were reported after a mean period of 18 mo after POP repair. As a first intervention, three patients underwent ablation of the prosthetic material (PM). As a second intervention, open proctectomy with a primary anastomosis, an omental patch, and a protective ileostomy were performed in two patients. One patient required a terminal colostomy due to complete destruction of the anal sphincters. In two other patients, ablation of the PM and proctectomy was performed as a one-step procedure. The postoperative course in all patients was uneventful, with a mean length of hospitalization of 20 d (range: 15-30). Closure of the ileostomy was achieved in all four patients within four months. After a mean period of 35 mo (range: 4-60) of follow-up, no recurrence was observed with normal continence in four patients. CONCLUSION: In our experience, the definitive treatment of high RVFs after PM repair for POP necessitates ablation of the PM, proctectomy with a primary colo-rectal anastomosis, an omental patch interposition, and a temporary ileostomy. PMID- 20572303 TI - Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. AB - AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2 related factor-2 (Nrf2)-antioxidant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four experimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfusion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the operation. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis. RESULTS: Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a significant increase in serum AST and ALT levels (AST: 260.13 +/- 40.17 U/L vs 186.00 +/- 24.21 U/L, P < 0.01; ALT: 139.63 +/- 11.35 U/L vs 48.38 +/- 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 +/- 40.17 U/L vs 216.63 +/- 22.65 U/L, P < 0.05; ALT: 139.63 +/- 11.35 U/L vs 97.63 +/- 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In addition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevated liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression. CONCLUSION: SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway. PMID- 20572305 TI - Vitamin D receptor gene polymorphisms and hepatocellular carcinoma in alcoholic cirrhosis. AB - AIM: To assess the relationship between vitamin D receptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucleotide gene polymorphisms of the VDR were investigated by polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was significantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was significantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively). CONCLUSION: VDR genetic polymorphisms are significantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology. PMID- 20572306 TI - Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. AB - AIM: To evaluate the relationship between glycemic control [assessed by glycated hemoglobin (HbA1c)], antidiabetic therapies and the risk of hepatocellular carcinoma (HCC). METHODS: We recruited 465 patients with HCC, 618 cases with liver cirrhosis and 490 controls with no liver disease. Among subjects with type 2 diabetes mellitus (DM2), the associations between the antidiabetic strategies and HbA1c level with HCC were determined through 2 series of multivariate logistic regression models using cirrhotic patients and controls as comparison groups. RESULTS: DM2 prevalence was 31.2% in patients with HCC, 23.2% in cirrhotic patients and 12.6% in controls (P < 0.0001). In 86% of study subjects, DM2 had been diagnosed for more than 1 year before the HCC diagnosis. HCC patients with DM2 had a 1.5-2.5-fold increased risk of liver cancer. The HbA1c mean levels were significantly higher in DM2 patients with HCC than in cirrhotic and control DM2 patients. Antidiabetic treatment with metformin was more common among cirrhotic and control DM2 subjects than among cases with HCC. In both series of multivariate analyses, treatment with metformin significantly reduced the risk of HCC by more than 80% compared with sulphonylureas and insulin therapy. No significant differences were seen between sulphonylureas and insulin treatment. Elevated HbA1c levels were positively related to the risk for HCC in diabetic patients, with a 26%-50% increase in risk for each 1% increase in HbA1c values. CONCLUSION: In patients with preexisting DM2, the risk of HCC is positively associated with poor chronic glycemic control and significantly decreased by metformin therapy. PMID- 20572308 TI - Predisposing factors and surgical outcome of complicated liver hydatid cysts. AB - AIM: To evaluate the predisposing factors for peritoneal perforation and intrabiliary rupture and the effects of these complications on surgical outcome in liver hydatid disease. METHODS: A total of 372 patients with liver hydatid cysts who had undergone surgical treatment were evaluated retrospectively. Twenty eight patients with peritoneal perforation, 93 patients with spontaneous intrabiliary perforation, and 251 patients with noncomplicated hydatid cysts were treated in our clinics. RESULTS: When the predisposing factors for complications were evaluated, younger age, superficial position, and larger cyst dimensions (P < 0.05; range, 0.001-0.017) increased peritoneal perforation rates. It was shown that older age increased cyst dimensions, and presence of multiple and bilobar cysts increased intrabiliary rupture rates (P < 0.05; range, 0.001-0.028). Partial pericystectomy and drainage was the most frequent surgical procedure in all groups (71.6%). The incidence of post-operative complications in the peritoneal perforated group, in the intrabiliary ruptured group, and in the noncomplicated group was 25%, 16.1% and 5.5%, respectively. When compared, complication rates were significantly different (P = 0.002). When length of hospital stay was compared, there was no significant difference between the groups (P > 0.05). The overall recurrence rate was 3.8% (14 patients), but there was not any statistical difference among the patient groups (P = 0.13). The early postoperative mortality rate was 1.1%. CONCLUSION: In peritoneally perforated and intrabiliary ruptured cases, the most important steps are irrigation of the peritoneal cavity and clearance of the cystic material from the biliary tree. PMID- 20572307 TI - Helicobacter pylori in dental plaque and stomach of patients from Northern Brazil. AB - AIM: To establish whether virulence factor genes vacA and cagA are present in Helicobacter pylori (H. pylori) retrieved from gastric mucosa and dental plaque in patients with dyspepsia. METHODS: Cumulative dental plaque specimens and gastric biopsies were submitted to histological examination, rapid urease test and polymerase chain reaction (PCR) assays to detect the presence of cagA and vacA polymorphisms. RESULTS: Detection of H. pylori from dental plaque and gastric biopsy samples was greater by PCR compared to histological examination and the rapid urease test. DNA from H. pylori was detected in 96% of gastric mucosa samples and in 72% of dental plaque samples. Sixty-three (89%) of 71 dental plaque samples that were H. pylori-positive also exhibited identical vacA and cagA genotypes in gastric mucosa. The most common genotype was vacAs1bm1 and cagA positive, either in dental plaque or gastric mucosa. These virulent H. pylori isolates were involved in the severity of clinical outcome. CONCLUSION: These pathogenic strains were found simultaneously in dental plaque and gastric mucosa, which suggests that gastric infection is correlated with the presence of H. pylori in the mouth. PMID- 20572309 TI - Is inconsistency of alpha-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence? AB - AIM: To identify the clinical outcomes of hepatocellular carcinoma (HCC) patients with inconsistent alpha-fetoprotein (AFP) levels which were initially high and then low at recurrence. METHODS: We retrospectively included 178 patients who underwent liver resection with high preoperative AFP levels (> or = 200 ng/dL). Sixty-nine HCC patients had recurrence during follow-up and were grouped by their AFP levels at recurrence: group I, AFP < or = 20 ng/dL (n = 16); group II, AFP 20 200 ng/dL (n = 24); and group III, AFP > or = 200 ng/dL (n = 29). Their preoperative clinical characteristics, accumulated recurrence rate, and recurrence-to-death survival rate were compared. Three patients, one in each group, underwent liver resection twice for primary and recurrent HCC. AFP immunohistochemistry of primary and recurrent HCC specimens were examined. RESULTS: In this study, 23% of patients demonstrated normal AFP levels at HCC recurrence. The AFP levels in these patients were initially high. There were no significant differences in clinical characteristics between the three groups except for the mean recurrence interval (21.8 +/- 14.6, 12.3 +/- 7.7, 8.3 +/- 6.6 mo, respectively, P < 0.001) and survival time (40.2 +/- 19.9, 36.1 +/- 22.4, 21.9 +/- 22.0 mo, respectively, P = 0.013). Tumor size > 5 cm, total bilirubin > 1.2 mg/dL, vessel invasion, Child classification B, group III, and recurrence interval < 12 mo, were risk factors for survival rate. Cox regression analysis was performed and vessel invasion, group III, and recurrence interval were independent risk factors. The recurrence interval was significant longer in group I (P < 0.001). The recurrence-to-death survival rate was significantly better in group II (P = 0.016). AFP staining was strong in the primary HCC specimens and was reduced at recurrence in group I specimens. CONCLUSION: Patients in group I with inconsistent AFP levels had a longer recurrence interval and worse recurrence-to-death survival rate than those in group II. This clinical presentation may be caused by a delay in the detection of HCC recurrence. PMID- 20572310 TI - Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes. AB - AIM: To analyze the combined treatment of resection and intraoperative radiofrequency ablation (RFA) for multifocal hepatocellular carcinoma in terms of prognosis and surgical outcomes. METHODS: This study was a retrospective case comparison study using prospectively collected data. The study covered the period from April 2001 to December 2006. The data of 200 patients with histologically confirmed hepatocellular carcinoma were reviewed. Nineteen patients (17 men and 2 women) having received resection in combination with RFA were chosen as subjects of the study (the combination group). Fifty-four patients (43 men and 11 women) having received resection alone were selected for comparison (the resection group). The two groups matched tumor number and tumor size, and all the patients in the two groups displayed no tumor rupture, major vascular involvement and distant metastasis. Their demographics, preoperative assessment, disease recurrence patterns, overall survival and disease-free survival were compared. RESULTS: In the combination group, the median age was 65 years (range, 34-77 years), the median tumor number was 3 (range, 2-9), and the median tumor size was 6 cm (range, 1.2-14 cm). In the resection group, the median age was 51.5 years (range, 27-80 years, P = 0.003), the median tumor number was 3 (range, 2-9, P = 0.574), and the median tumor size was 6 cm (range, 1-14 cm, P = 0.782). The two groups were similar in characteristics of tumors and comorbidities, and had comparable results in preoperative liver function tests. All patients had Child Pugh class A status. Bilobar involvement occurred in 14 patients (73.6%) in the combination group and 3 patients (5.5%) in the resection group (P = 0.04). Six patients (32%) in the combination group and 35 patients (65%) in the resection group underwent major hepatectomy. Thirteen patients (68%) in the combination group and 19 patients (35%) in the resection group underwent minor hepatectomy (P = 0.012). The combination group had fewer major resections (32% vs 65%, P = 0.012), less blood loss (400 vs 657 mL, P = 0.007), shorter operation time (270 vs 400 min, P = 0.001), and shorter hospital stay (7 vs 8.5 d, P = 0.042). The two groups displayed no major differences in surgical complications (15.8% vs 31.5%, P = 0.24), disease recurrence (63.2% vs 50%, P = 0.673), hospital mortality (5.3% vs 5.6%, P = 1), and overall survival (53 vs 44.5 mo, P = 0.496). CONCLUSION: Safe and effective for selected patients with multifocal hepatocellular carcinoma, the combination of resection and intraoperative RFA widens the applicability of surgical intervention for the disease. PMID- 20572311 TI - Evidence-based appraisal in laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease. AB - AIM: To demonstrate the optimal surgical procedure for gastroesophageal reflux disease. METHODS: The electronic databases of Medline, Elsevier, Springerlink and Embase over the last 16 years were searched. All clinical trials involved in the outcomes of laparoscopic Nissen fundoplication (LNF) and laparoscopic Toupet fundoplication (LTF) were identified. The data of assessment in benefits and adverse results of LNF and LTF were extracted and compared using meta-analysis. RESULTS: We ultimately identified a total of 32 references reporting nine randomized controlled trials, eight prospective cohort trials and 15 retrospective trials. These studies reported a total of 6236 patients, of whom 4252 (68.18%) underwent LNF and 1984 (31.82%) underwent LTF. There were no differences between LNF and LTF in patients' satisfaction, perioperative complications, postoperative heartburn, reflux recurrence and re-operation. Both LNF and LTF enhanced the function of lower esophageal sphincter and improved esophagitis. The postoperative dysphagia, gas-bloating syndrome, inability to belch and the need for dilatation after LNF were more common than after LTF. Subgroup analyses showed that dysphagia after LNF and LTF was similar in patients with normal esophageal peristalsis (EP), but occurred more frequently in patients with weak EP after LNF than after LTF. Furthermore, patients with normal EP after LNF still had a higher risk of developing dysphagia than did patients with abnormal EP after LTF. CONCLUSION: Compared with LNF, LTF offers equivalent symptom relief and reduces adverse results. PMID- 20572312 TI - Simultaneous detection of different serum pepsinogens and its primary application. AB - AIM: To develop the simple, rapid and sensitive dual-label time-resolved fluoroimmunoassay for pepsinogens in human serum. METHODS: Based on two-site sandwich protocol, monoclonal antibodies (McAbs) against pepsinogen I (PG I) and PG II were co-coated in 96 microtitration wells, and tracer McAbs against PG I and PG II were labeled with europium (Eu) and samarium (Sm) chelate, respectively. Diluted serum samples of Eu(3+)- and Sm(3+)-McAbs were added into microtitration wells simultaneously. After washing, fluorescence of bound Sm(3+) and Eu(3+) tracers was detected. RESULTS: The detection limit was 0.2 microg/L for PG I and 0.05 microg/L for PG II. The assay range was 5.0-320.0 microg/L for PG I and 1.0-55.0 microg/L for PG II. The average recovery rate was 102.7% for PG I and 98.8% for PG II. Sera from healthy controls and patients with gastric disease were analyzed. The PG detected by dual-label assay was in good agreement with that detected by single-label assay or by enzyme-linked immunosorbent assay. CONCLUSION: Dual-label assay can provide high-throughput serological screening for gastric diseases. PMID- 20572314 TI - Obstructing fungal cholangitis complicating metal biliary stent placement in pancreatic cancer. AB - Biliary obstructions can lead to infections of the biliary system, particularly in patients with occluded biliary stents. Fungal organisms are frequently found in biliary aspirates of patients who have been on antibiotics and have stents; however, fungal masses, or "balls", that fully obstruct the biliary system are uncommon and exceedingly difficult to eradicate. We present 4 cases of obstructing fungal cholangitis in patients who had metal biliary stents placed for pancreatic malignancies, and subsequently required aggressive antifungal administration along with endoscopic and radiologic interventions. This report also reviews approaches previously undertaken to manage severe obstructing fungal cholangitis. PMID- 20572313 TI - Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector. AB - AIM: To generate recombinant adenoviral vector containing calreticulin (CRT) hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine. METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease digestion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5' end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinantion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombinant adenoviral vector to package and amplify recombinant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expression of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting. RESULTS: The CRT-HBsAg fusion gene was characterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT HBsAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 x 10(11) pfu/mL. The CRT-HBsAg fusion protein was expressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B virus gene therapy. PMID- 20572316 TI - Diabetes drug safety update: Avandia and your heart. PMID- 20572315 TI - Stone extraction balloon-guided repeat self-expanding metal stent placement. AB - Self-expanding metal stent (SEMS) placement offers safe and effective palliation in patients with upper gastrointestinal obstruction due to a malignancy. Well described complications of SEMS placement include tumor growth, obstruction, and stent migration. SEMS occlusions are treated by SEMS redeployment, argon plasma coagulation application, balloon dilation, and surgical bypass. At our center, we usually place the second SEMS into the first SEMS if there is complete occlusion by the tumor. We discovered an unusual complication during SEMS redeployment. The guidewire passed through the mesh of the first SEMS and caused the second SEMS to become entangled with the first SEMS. This led to the distortion and malfunction of the second SEMS, which worsened the gastric outlet obstruction. For lowering the risk of entanglement, we studied stone extraction balloon-guided repeat SEMS placement. This is the first report of a SEMS entangled by the mesh of the first SEMS and stone extraction balloon-guided repeat SEMS placement for lowering the risk of this complication. PMID- 20572317 TI - Healing the caregiver. Six steps to help you stay healthy while caring for a loved one. PMID- 20572318 TI - Shining the spotlight on vitamin D. New research seeks to pinpoint the role of this key nutrient. PMID- 20572319 TI - Tips for healthy travel. Simple preparations can help make your next trip a safe one. PMID- 20572320 TI - I suffer from frequent leg cramps and I've heard that quinine can help. Should I consider taking it? PMID- 20572321 TI - Recent FDA approvals and changes. PMID- 20572322 TI - Kids with HCV go undiagnosed and untreated. PMID- 20572323 TI - [Political violence and partner violence]. PMID- 20572324 TI - [Danish pigs are of world class, 2]. PMID- 20572325 TI - Swiss Congress of Nuclear Medicine 2010. PMID- 20572326 TI - ROOBY study: a critical view. PMID- 20572327 TI - Innovations in preventing and managing chronic conditions: what's working in the real world? AB - Wellness and prevention strategies are fast becoming a standard feature of employer-based health benefits in hopes of countering rapidly rising health care costs that drive higher insurance premiums. At the same time, payers and health care providers are experimenting with how to improve care coordination for high cost patients with multiple chronic conditions, an ongoing challenge in the fragmented U.S. health care system. Promoting health and wellness and improving the care of people with chronic conditions offer promise in helping to improve the value of health care and control costs, according to experts at a Center for Studying Health System Change (HSC) conference titled, Innovations in Preventing and Managing Chronic Conditions: What's Working in the Real World? Panelists explored how effective employer-sponsored wellness and prevention initiatives focus on health improvement as a business strategy and foster work and community environments that help people lower risk factors--smoking, diet, lack of exercise -that lead to disease. Panelists also discussed various models--centered on strong primary care-to improve care for people with chronic conditions. PMID- 20572328 TI - Cystatin C and glomerular filtration rate. PMID- 20572329 TI - Nursing is a good choice for a second career. PMID- 20572330 TI - Nursing as a second career: have you found your true calling? Interview by Erin Wyatt. AB - Nursing is a noble profession involving much hard work but pays off in abundance. Some nurses have known since childhood what they wanted to be when they grew up, whereas others didn't decide until they switched majors a few times in college. Then there are those who didn't find out that nursing was meant for them until later-years later. PMID- 20572332 TI - Manage diarrhea and skin effects from lapatinib. PMID- 20572331 TI - Why did you leave your first career to become an oncology nurse? PMID- 20572333 TI - Halt the hazards of hand hygiene. PMID- 20572334 TI - Gene may cause tamoxifen resistance. PMID- 20572335 TI - [SiRNA targeting ICP4 attenuates HSV-1 replication]. AB - HSV-1, a neurotropic virus, always leads to severe nervous symptoms. It is hard to completely eradicate the latent viruses after conventional therapy so that recurrence is inevitable. ICP is a key regulator for HSV replication and transcription that determines the cytolytic infection or latent state. In search of new anti-virus strategy targeting HSV-1ICP4, two pairs of siRNA were designed, and a recombinant eukaryotic lentiviral expression plasmid pLKO-puro(r)-hU6-siRNA was constructed. Vero cells were transfected with the designed siRNAs by Lipofectamine 2000 and four stable monoclonal cell lines were established by puromycin screening method. The ICP4 expression at mRNA level was detected with real-time PCR, and the HSV-1 replication was measured with TCID50 assay. SiRNA was shown as an effective way to inhibit the expression of ICP4 in monoclonal cell lines. Meanwhile, HSV-1 replication was significantly inhibited when ICP4 was shut down by siRNA. We conclude that siRNA targeting ICP4 attenuates HSV-1 replication. Further more, multi-site siRNAs show stronger inhibitory effect on viral replication, which may be an effective and feasible approach for biological anti-viral drugs. PMID- 20572336 TI - [DNA vaccination via in vivo electroporation can elicit specific immune response against highly pathogenic H5N1 influenza viral structural antigens in mice]. AB - This study aims to develop inexpensive and effective experimental vaccines against highly pathogenic H5N1 Avian Influenza (HPAI) virus and to optimize their immunization programs. To this end, we first synthesized the codon-optimized hemagglutinin gene (HAop) and neuraminidase gene (NAop), both of which were derived from a H5N1 virus (Anhui strain), and constructed successfully the DNA vaccines containing a single cistronic construct (HAwt, HAop, or NAop) or a bicistronic construct (HAop/M2 or NAop/M1) of H5N1 influenza virus origin. Their expression was confirmed by indirect immunofluorescent assay (IFA) and Western blotting. Then twice vaccination of mice with the DNA vaccines by injection intramuscularly or in vivo electroporation (EP) via two different routes was evaluated and analyzed by hemagglutination inhibition (HI) assay, NA-specific antibody detection, micro-neutralizing antibody test and IFN-gamma ELISpot assay. Our results showed that the DNA vaccines with coden-optimized HAop and NAop constructs could quickly elicit a strong immune response by in vivo EP, especially the cellular immune response against HA and NA; the in vivo EP via intradermal route induced stronger humoral immune responses than those via intramuscular route. Our findings will pave a way for further development of novel DNA-based H5N1 vaccine and for the optimization of the immunization programs of DNA vaccine. PMID- 20572338 TI - [Molecular analysis of an avian influenza virus isolate of H5N2 subtype from parrot]. AB - In 2005, an avian influenza virus stain was isolated from Parrot in Guangdong, which was then genotyped as H5N2 subtype and designated as A/Parrot/Guangdong/268/2005. According to the current OIE definition on the low pathogenicity of avian influenza virus, the strain was recognized as a low pathogenic avian influenza virus due to the presence of one basic amino acid residue at the HA cleavage site. Some molecular characteristics of the virus, such as potential glycosylation sites in HA and NA, receptor binding sites of HA, and drug resistance site of NA, showed no variations. To analyze molecular evolution of this strain, we selected the sequences of H5N2 subtype AIVs from GenBank and established the phylogenetic trees. Our results indicated that this strain shared the highest homologies with the H5N2 LPAI isolate A/Pheasant/NJ/1355/1998-like. Phylogenic analysis revealed the isolate, together with A/Chicken/Pennsylvania/1/1983 (H5N2), belonged to America lineages and clustered with A/Pheasant/NJ/1355/1998-like. PMID- 20572337 TI - [Cloning and analysis of full-length genes of a H9N2 subtype avian influenza virus isolated from Guangdong]. AB - Eight full-length genes of an avian influenza virus Chinese isolate of H9N2 subtype, A/Chicken/Guangdong/HL/2006 (H9N2) (abbreviated as Ck/GD/HL/06), were amplified by RT-PCR, including the 5' and 3' non-coding region. All the genes were cloned and sequenced. The phylogenetic analysis results showed the HA gene of Ck/GD/HL/06 was located in the same phylogenetic clade as Dk/HK/Y280/97 (H9N2), while the Dk/HK/Y280/97-like viruses had been predominately isolated from chickens in mainland China. After the analysis of glycosylation sites and receptor-binding sites in the HA, it was shown that the HA of Ck/GD/HL/06 exhibited the common feature of H9 subtype avian influenza virus isolated from China, but the leucine (Leu) residue at the amino acid position 226 indicated the potential of binding with SA alpha,2-6 receptor. The three internal genes of Ck/GD/HL/06 (PB1, PA and NP) had the highest nucleotide identity with A/Viet Nam/1203/2004 (abbreviated A/VN/1203/04) isolate, which was shown to be transmitted from chickens to human and caused lethal infection in human. No analogous H9N2 strains was reported in previous studies. Based on the high similarity of Ck/GD/HL/06 three genes to A/VN/1203/04, it was suggested that the possibility of generating new highly pathogenic H5N1 AIVs by recombination was worthy of our attention. Further studies should be needed for molecular epidemiologic surveillance of H9N2 AIV in the south China for a long time. PMID- 20572339 TI - [Construction, expression and immunogenicity analysis of a fusion protein containing M2e of influenza A virus fused to a modified Pseudomonas aeruginosa exotoxin A]. AB - M2 protein of type A influenza virus is a good candidate for universal influenza vaccine, exotoxin A of Pseudomonas aeruginosa may facilitate the immunogenicity of M2 protein. We constructed and expressed a prokaryotic expression plasmid containing a chimeric gene of M2 extracellular coding region and a partial PEA gene, and observed the immunoprotection in BALB/c mice vaccinated with the fusion protein. The fusion protein (ntPE-M2e) was generated by inserting the coding sequence of the M2e in place of Ib loop in PEA. This fusion protein was used to immunize BALB/c mice by subcutaneously injection with incomplete Freund's adjuvant and boost at weeks 3 and 7. The immunized mice were challenged with influenza virus strain A/PR/34/8. The fusion protein (ntPE-M2e) immunization protected mice against lethal viral challenge. ELISA and ELISPOT results demonstrated that the fusion protein could induce a strong systemic immune response against synthetic M2e peptide, and virus replication in the lungs of mice was inhibited in comparison with the control. This study provides foundation for developing broad-spectrum vaccines against type A influenza viruses. PMID- 20572340 TI - [Analysis of full-length gene sequence of a rabies vaccine strain CTN-1 for human use in China]. AB - CTN-1 is one of the rabies vaccine strains for human use in China, but there has been no report on the full-length gene sequence of CTN-1. In this study, the full length gene of CTN-1 was amplified by RT-PCR, each PCR product was cloned into T vector and then sequenced, assemblied and compared with other vaccine strains as well as the wild Chinese rabies isolates. The phylogenetic tree of G gene was constructed and the genetic homology was analyzed. The results revealed that CTN 1 was 11 925nt (GenBank accession number: FJ959397)in length and belonged to the genotype I. The full-length nucleotide homologies among CTN-1 and other rabies virus strains were between 81.5%-93.4%, of which the lowest 81.5% was between CTN 1 strain and bat isolate SHBRV, and the highest 93.4% was between CTN-1 and Chinese isolate HN10. The phylogenetic analysis revealed that the majority of Chinese isolates could be grouped into the same clade with the CTN-1 strain, but aG and some vaccine strains from abroad such as Flury, PM, PV, ERA, RC-HL and a few Chinese strains were grouped in another clade. Comparsion of the G protein genes also showed that the homologies among CTN-1 and most of the Chinese isolates were higher than that of the other vaccine strains to those Chinese strains. Therefore, it suggests that the CTN-1 strain is more suitable and rational to be used for the production of rabies inactivated vaccine in China than the others. PMID- 20572341 TI - [Molecular epidemiological characteristics of norovirus gastroenteritis outbreaks in Guangdong from 2005 to 2008]. AB - To study the molecular epidemiological characteristics of norovirus gastroenteritis outbreaks in Guangdong, we collected fecal and anal swabs specimens from 24 outbreaks of acute gastroenteritis from 2005 to 2008 to detect norovirus. Specimens were detected by RT-PCR and then sequenced. The descriptive data were also collected. According to our research, 19 of 24 outbreaks of gastroenteritis were positive for norovirus. The occurrence time was from October to next February mainly. The strains in 2005 belonged to G II-3 genotype and all outbreaks occurred in kindergarten and school. But from autumn of 2006, the outbreaks were all caused by G II-4/2006b variant and occurred in universities and community. The number of outbreaks in 2007 increased greatly and covered all over province. The nucleotide sequences of Guangdong strains in some sites showed high regional identity. Our results showed that with the shift of genotype from G II-3 to G II-4, occurrence of norovirus outbreaks increased greatly. The outbreaks of norovirus caused by G II-4/2006b variant spreaded widely and the involved population covered children and adult, indicating the strong invasiveness of this variant. PMID- 20572342 TI - [Expression and immunity of multi-HIV B'/C subype genes in replicating DNA vaccines]. AB - To understand the effect of various gene structures of HIV B'/C subtype on the gene expression and immunity in DNA vaccine, replicating DNA vector pSCK2 was used to construct seven DNA vaccines carrying one or more of HIV B'/C subtype genes: gagpol, gp160 and rtn (rev, tat and nef fusion gene). Immunofluorescence staining indicated that Gag, Gp160, Rev, Tat and Nef could be expressed from the seven DNA vaccines. Stronger expression was observed with the gene in single-gene expression plasmid or with the gene located at upper-IRES in double- or multi gene expression plasmid. ELISA test showed that Gag induced higher antibody response, but the antibody titers stimulated by Gp160, Pol, or RTN were very low. Both Gag single-gene expression plasmid and Gag-RTN double-gene expression plasmid separately inoculating induced stronger antibody response against Gag than Gag-Gp160 double-gene expression plasmid and Gagpol-Gp160-RTN multi-gene expression plasmid or combined inoculation of Gag and Gp160 single-gene expression plasmids did. ELISPOT detection showed that all the seven DNA vaccines could stimulate cellular immune response against Gag, Pol, Gp160, Tat, and Nef, respectively. Gagpol or Gp160 single-gene expression plasmid separately inoculating stimulated the strongest cellular immune response. Tat and Nef expressed in all the plasmids induced similar immune response. These results indicated that HIV B'/C subtype genes gagpol, gp160 and rtn could be efficiently expressed in the replicating DNA vaccine vector, single-gene expression plasmid had the higher gene expression level and induced stronger immune response; combined immunization of Gagpol and Gp160 had dramatically lower immunity than Gagpol or Gp160 separated immunization did. Immunity of RTN had no difference between combined and separated immunizations. Therefore, in case of immunization with DNA vaccines containing different HIV genes, it is necessary to optimize the combined immunization procedure, especially for the combination of Gag and Gp160 containing vaccines. PMID- 20572343 TI - [Construction and identification of recombinant adeno-associated virus expressing siRNA]. AB - Adeno-associated virus (AAV) mediated RNA interference can be used to inhibit the expression of homologous genes in different mammalian cells. In this study, a transfer plasmid (pAAV-EGFP-H1) containing the H1 promoter and EGFP-expressing cassette was constructed based on the backbone of pAAV-MCS. Using calcium phosphate precipitation method, pAAV-EGFP-H1 was co-transfected into AAV-293 cells with helper plasmids and infective recombinant AAV was generated. EGFP gene was selected as the interfering target. EGFP gene was removed from pAAV-EGFP-H1 and a new transfer plasmid pAAV-H1 was constructed. Recombinant AAV-H1-shEGFP then infected 293 cells which was pre-transfected with plasmid pEGFP-N1. After 72 hours, the interference effect on EGFP expression was investigated by fluorescence microscope, fluorescence quantitative PCR and fluorescence activated cell sorting (FACS). All results showed that rAAV-H1-shEGFP could effectively reduce more than 60 percent of EGFP expression in 293 cells. The study demonstrates that a recombinant AAV transfer plasmid for RNAi is constructed, and the generated recombinant AAV can be used for further investigation on RNAi research. PMID- 20572344 TI - [The enhancement of DNA binding ability of a mutated E2 (A338V) protein of HPV 2]. AB - HPV-2 is a very common type of HPV which causes common warts. The E2 protein of virus can repress the activity of the viral early promoter through binding to the specific binding sites in viral LCR. Previously we reported that the repression of a mutated E2 protein of HPV-2 isolated from a patient with huge common wart on the viral early promoter was obviously decreased, and A338V mutation located at the C terminal DNA binding region of E2 protein. In this study, we expressed and purified the recombinant mutated and prototype E2 fusion proteins, both in the contexts of the C terminal and the full length, by prokaryotic expression system. The electrophoretic mobility shift assay showed E2 protein could bind to double stranded DNA oligos labeled with biotin that covered two E2 binding sites. The DNA binding abilities of both C terminal and full-length mutated E2 proteins were stronger than the prototype analogs. This result indicates that the enhancement of the mutated E2 DNA binding ability may be the molecular mechanism for its impact on the activity of viral promoter, which correlates with the phenotype of extensive common wart. PMID- 20572345 TI - [Molecular basis of one-way serological reaction between SINV and XJ-160 virus]. AB - The purpose of this study is to elucidate the molecular mechanism of one-way serological reaction between XJ-160 virus and SINV by recombinant viruses which exchanged the glycoprotein genes individually or simultaneously. Three recombinant viruses were obtained based on the whole-length infectious cDNA clone of XJ-160 virus. The infectivity and pathogenesis to BHK-21 cells and animals were studied and the gene which controlled this one-way serological reaction phenomenon was searched by MCPENT. The results showed that the E2 glycoprotein was the main factor which influenced the growth rate, plaque morphology and pathogenicity of BHK-21 cells and suckling mice. The results of MCPENT showed that the E2 glycoprotein of SINV played a major role in this one-way serological reaction phenomenon. Our study identified the SINE2 gene was the determined gene for one way serological reaction between XJ-160 virus and SINV, and this research laid the foundation for further analysis of the genomic structure and function of SINV. PMID- 20572346 TI - [Seroepidemiological survey of sheep hepatitis E virus infection in Aksu region of Xinjiang Autonomous]. AB - Four hundreds and ninety sheep sera from seven breeds raised at eight counties and one city of Aksu region in Xinjiang were tested by ELISA for the presence of antibodies against hepatitis E virus (HEV), and the positive rate differences were compared based on administrative areas, breeds and age by Chi-square test. The result showed that the general positive rate was 28.98% (142/490), the positive rate were 35.44% (28/79), 29.67% (27/91), 20% (4/20), 40% (12/30), 32.5% (26/80), 38% (19/50), 22.5% (9/40), 8% (4/50) and 26% (13/50) respectively in eight counties and one city, there was a significant difference between Xayar and other administrative areas (P<0.01); there was also a significant difference among age ranges (P<0.01), being 38.75% (31/80) over 2 years old, 15.45% (17/110) below 1 year old; The seroprevalence was still related to breeds, i. e. there was a significant difference between Mongolia sheep and other breeds (P<0.01). From these data, it is confirmed that there is a possibility of previous and potential infection of sheep HEV in Aksu region of Xinjiang Autonomous. PMID- 20572347 TI - [Genome sequencing and analysis of the bovine viral diarrhea virus-2 strain JZ05 1 isolated in China]. AB - Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, which is a widespread problem for beef and dairy herds, and has given rise to a significant loss in the livestock industry all over the world. The BVDV strain JZ05-1 isolated from cattle in Jilin, China generated cytopathic effect (CPE) in MDBK cells. Eight overlapped gene fragments were amplified by RT-PCR and sequenced, the complete genom sequence of BVDV strain JZ05-1 was assembled. According to the results, the JZ05-1 genome was composed of 12285 nucleotides in length (GenBank accession No. GQ888686), which could be divided into three regions: a 387 nt 5'-untranslated region (UTR), a 11694 nt single large open reading frame encoding a polyprotein, and a 204 nt 3'-UTR. The 5'-UTR and genome sequences were analyzed by sequence alignment and construction of phylogenetic trees. The strain JZ05-1 was classified as BVDV type 2a. The BVDV-2 strain JZ05-1 genome showed high similarity to the p11Q isolated in Canada and the XJ-04 isolated in China, with 90% and 91% identity in nucleotide sequence, respectively. Compared with the similarity within the BVDV-2 genotype (96%), the JZ05-1 had low sequence similarity to other BVDV-2 strains. PMID- 20572348 TI - [ShRNA against NSP4 gene inhibits the proliferation of bovine rotavirus in vitro]. AB - Based on the NSP4 sequence of bovine rotavirus (BRV), the shRNA was designed and synthesized, and a shRNA recombinant lenti-virus vector RNAi-H1-89 was constructed. The recombinant RNAi-H1-89 Lenti-virus was packaged by transfecting the 293T cell with the recombinant vector RNAi-H1-89 and two helper plasmids using lipofectamine, and then used to infect MA104 cells. The MA104 cells were further infected with BRV strain G6 24h post-infection, with the LacZ shRNA recombinant lenti-virus as control. Thirty-six hours later, the CPE of the infected cells was observed under microscope, shRNA of NSP4 gene inhibited CPE in MA104 cell; the shRNA against NSP4 gene also inhibited NSP4 gene expression by RT PCR, The virus titer in the cell culture supernatant was significant lower compared with the control group. The above results showed that RNAi-H1-89 against NSP4 gene could specifically silence NSP4 gene expression, and inhibit the proliferation of BRV. PMID- 20572349 TI - [Comparisons of different methods for virus-elimination of edible fungi]. AB - Four dsRNA bands were extracted from Pleurotus ostreatus TD300 by the dsRNA isolation technique with sizes of 8.2 kb, 2.5 kb, 2.1 kb, and 1.1 kb, respectively. Four virus-eliminated methods, i. e. hyphal tips cut (HTC), protoplast regeneration (PR), single spore hybridization (SSH), and frozen and lyophilized (FL), were applied to prepare virus-eliminated strains, and one virus eliminated strain was selected for each virus-elimination method. The virus eliminated strains were named as HTC8, PR15, FL01, and SSH11, respectively. There were low concentration of 8.2 kb dsRNA remained in HTC8, as well as low concentration of 8.2 kb and 2.5 kb dsRNA remained in FL01. However, no dsRNA remained in PR15 and SSH11. The hyphal growth rate and laccase activity of the virus-eliminated strains increased, especially HTC8 and PR15, whose hyphal growth rate was higher by 22.73% and 18.18%, and laccase activities higher by 145.83% and 134.38% than that of the original strain, respectively. The conclusion is that hyphal tips cut and protoplast regeneration are suitable to prepare virus eliminated strains of edible fungi. PMID- 20572350 TI - [Genetic diversity of porcine sapoviruses from Lulong county in China]. AB - Porcine sapoviruses (SaVs), which belong to the family Caliciviridae, have been considered potential zoonotic agents for human infection, and several cases have been reported in Asian countries. In this study, a total of 200 porcine fecal samples collected from Lulong county of China were tested. Among 200 samples, porcine sapoviruses were detected by RT-PCR in 17 samples (8.5%) showing their circulation in China. 14 out of 17 positive sapovirus strains were genetically related to the genogroup III (GIII) and were further divided into three different clusters or genotypes according to the phylogenetic analysis. In addition, the remaining three sapovirus strains belonged to GVII (one strain) and a potential novel genogroup (two strains) according to the phylogenetic analysis and the nucleotide identity and amino acid identity. These data suggested the genetic diversity of porcine sapoviruses in China. PMID- 20572351 TI - [A mucosal immune cells homing and infection of HIV]. PMID- 20572352 TI - [The rhythm of cardiology]. PMID- 20572353 TI - [Preoperative cardiac assessment before non-cardiac surgery: cardiac risk stratification]. AB - Perioperative cardiac events occurring in patients undergoing non-cardiac surgery are a common cause of morbidity and mortality. Current guidelines recommend an individualized approach to preoperative cardiac risk stratification prior to non cardiac surgery, integrating risk factors both for the patient (active cardiac conditions, clinical risk factors, functional capacity) and for the planned surgery. Preoperative cardiac investigations are currently limited to high-risk patients in whom they may contribute to modify the perioperative management. A multidisciplinary approach to such patients, integrating the general practitioner, is recommended in order to define an individualized peri-operative strategy. PMID- 20572354 TI - [Pre-operative cardiac assessment in non-cardiac surgery: a frequent dilemma simplified by a decision tree]. AB - In patients undergoing non-cardiac surgery, cardiac events are the most common cause of perioperative morbidity and mortality. It is often difficult to choose adequate cardiologic examinations before surgery. This paper, inspired by the guidelines of the European and American societies of cardiology (ESC, AHA, ACC), discusses the place of standard ECG, echocardiography, treadmill or bicycle ergometer and pharmacological stress testing in preoperative evaluations. The role of coronary angiography and prophylactic revascularization will also be discussed. Finally, we provide a decision tree which will be helpful to both general practitioners and specialists. PMID- 20572355 TI - [Long-term pursuit of endurance sport: a new risk factor for atrial fibrillation?]. AB - Long-term pursuit of endurance sport: a new risk factor for atrial fibrillation? Lone atrial fibrillation is a term used when the arrhythmia develops in patients under 60 years old without any underlying cardiovascular disease. The aetiology is currently unknown but some recent data suggest that there is an association between a life-long practice of the endurance sport and atrial fibrillation. Long term structural changes in the left atrium and increased vagal tone related to high intensity training are the main hypothesized mechanisms. The best therapeutic approach is still unknown but radiofrequency catheter ablation can become the treatment of choice for this kind of patient. PMID- 20572356 TI - [Clopidogrel and its salts: any clnical implication?]. AB - Clopidogrel hydrogen sulfate is an antiplatelet agent administered, alone or in combination with acetyl salicylic acid, approved in the prevention of cardiovascular events based on large-scale clinical trials. The new salt formulations clopidogrel where approved based on pharmacokinetic measurements of the inactive prodrug on few healthy volunteers, without any other medication. Clopidogrel hydrogen sulfate has a wide variability in platelet response and the pharmacokinetic of the active metabolite is not dose-linear. Ideally, new clopidogrel salts should be tested for therapeutic equivalence in the target patient population. Should this not be feasible, consistent bioequivalence data should be obtained for the active metabolite, using a properly validated and standardized test method. PMID- 20572357 TI - [Cardiologic follow up of an oncologic patient]. AB - Recent progress in cancer therapy has dramatically modified the course and prognosis of some malignancies. Chemo and radiotherapy, along with newer targeted treatments, are given to control symptoms, postpone relapse, or attempt cure. However, many of these regimens are associated with adverse cardiovascular effects such as impaired left ventricular function, myocardial ischemia, hypertension, and arrhythmia. Awareness of potential cardiotoxicity is important, as it may allow practitioners to recognize early signs of cardiac complications and to adapt therapy in order to limit detrimental effects. Diagnosis of cardiovascular complications may iustify the introduction of cardiologic therapies, and may require the reassessment of risk/benefit ratios related to specific cancer therapy. Screening and follow up strategies are proposed. PMID- 20572358 TI - [Idiopathic premature ventricular complexes originating from the ventricular outflow tract: evaluation, prognosis and management]. AB - Idiopathic premature ventricular complexes originating from the ventricular outflow tract: evaluation, prognosis and management The prognosis of ventricular premature complexes (VPC) in the absence of heart disease is considered benign. VPC usually originate from the right or, less commonly, left ventricular outflow tract. QRS complexes therefore usually assume a left bundle branch block and inferior axis morphology. These VPC, particularly if very frequent (> 20,000 per day), may adversely affect left ventricular function and their suppression can restore normal function. Moreover, there is a clinical overlap with arrhythmogenic right ventricular dysplasia and this diagnosis should be considered when facing a left bundle branch block shaped VPC. However, the prognosis of outflow tract VPC is good for appropriately selected patients with normal left ventricular function, absence of syncope or ventricular tachycardia, and no evidence of cardiac disease. PMID- 20572359 TI - [Endovascular treatment of below the knee arteries in critical limb ischemia]. AB - Lower extremity peripheral arterial disease (PAD) may cause claudication or in the late phase critical limb ischemia (CLI). Due to the constant aging of the population and an increased prevalence of diabetes, CLI has become a major clinical concern for every vascular specialist. CLI is defined as the presence of ischemic rest pain or foot ulcers and a hypoperfusion of the foot. In case of CLI, rapid revascularisation is mandatory, and failure may imply lower limb amputation. Thanks to improvement in technique and equipment, endovascular revascularisation is associated with very promising limb salvage rate. In many centers, this minimally invasive approach has become the treatment of choice for the majority of patients with CLI. This review illustrates the different techniques and the data for infra-popliteal endovascular interventions. PMID- 20572361 TI - [And if the case is over?]. PMID- 20572360 TI - [Paravalvular leak following surgical valve replacement: is there a role for percutaneous paravalvular leak reduction?]. AB - After valve replacement, significant paravalvular leaks (PVL) may develop in up to 12.5% of the cases. Signs and symptoms include congestive heart failure and/or haemolysis and therefore may require reintervention. Redo valve surgery is considered the therapy of choice for symptomatic patients, either by valve replacement or leak repair. Considering the risk of morbidity and mortality associated with a surgical reintervention and the high post-surgical recurrence of PVL, the endovascular treatment represents an attractive alternative to surgery for high risk patients. The percutaneous approach aims at PVL reduction by implantation of certain occluder devices. The procedure is technically feasible in 60 to 90% of the cases according to different series. Technical success is associated with clinical improvement in 50 to 80% of the cases. PMID- 20572362 TI - [Emerging treatments for multiple sclerosis]. PMID- 20572363 TI - [Pentecost 2010: has man "created life"?]. PMID- 20572364 TI - [Kant, the mother who bore him, human dignity]. PMID- 20572365 TI - [Artifice and the encounter with life]. PMID- 20572366 TI - Atmospheric transformation of diesel emissions. AB - The hypothesis of this study was that exposing diesel exhaust (DE*) to the atmosphere transforms its composition and toxicity. Our specific aims were (1) to characterize the gas- and particle-phase products of atmospheric transformations of DE under the influence of daylight, ozone (O3), hydroxyl (OH) radicals, and nitrate (NO3) radicals; and (2) to explore the biologic activity of DE before and after the transformations took place. The study was executed with the aid of the EUPHORE (European Photoreactor) outdoor simulation chamber facility in Valencia, Spain. EUPHORE is one of the largest and best-equipped facilities of its kind in the world, allowing investigation of atmospheric transformation processes under realistic ambient conditions (with dilutions in the range of 1:300). DE was generated on-site using a modern light-duty diesel engine and a dynamometer system equipped with a continuous emission-gas analyzer. The engine (a turbocharged, intercooled model with common-rail direct injection) was obtained from the Ford Motor Company. A first series of experiments was carried out in January 2005 (the winter 2005 campaign), a second in May 2005 (the summer 2005 campaign), and a third in May and June 2006 (the summer 2006 campaign). The diesel fuel that was used closely matched the one currently in use in most of the United States (containing 47 ppm sulfur and 15% aromatic compounds). Our experiments examined the effects on the composition of DE aged in the dark with added NO3 radicals and of DE aged in daylight with added OH radicals both with and without added volatile organic compounds (VOCs). In order to remove excess nitrogen oxides (NO(x)), a NO(x) denuder was devised and used to conduct experiments in realistic low-NO(x) conditions in both summer campaigns. A scanning mobility particle sizer was used to determine the particle size and the number and volume concentrations of particulate matter (PM) in the DE. O3, NO(x), and reactive nitrogen oxides (NO(y)) were monitored using chemiluminescence and Fourier transform infrared instruments. At the end of the exposures, samples of particle-associated and semivolatile organic compounds (SVOCs) were collected from the chamber for chemical analysis using an XAD-coated annular denuder followed by a filter and XAD cartridge. (XAD is an adsorbent polystyrene divinylbenzene resin used in sampling cartridges.) Samples for toxicity testing were collected using Teflon filters followed by two XAD cartridges. The chemical analyses included determination of organic carbon (OC), elemental carbon (EC), carbon fractions, inorganic ions (e.g., sulfate and nitrate), and speciated organic compounds (polycyclic aromatic hydrocarbons [PAHs], nitro-PAHs, polar compounds, alkanes, hopanes, and steranes). The toxicity tests were performed with extracts of PM combined with the SVOCs. The biologic activity of these extracts was evaluated in vivo by instilling them into the tracheas of rodents and measuring pulmonary toxicity, inflammation, and oxidative-stress responses. Results from the chemical analyses indicated that aging DE in the dark with added NO3 radicals and aging DE in daylight with and without additions led to the formation of additional particles and SVOC mass caused by reactions of VOCs, SVOCs, and inorganic gases. The greatest increase in mass occurred with the addition of VOCs as co-reactants. The proportions of the pyrolized OC (POC) fraction increased in the organic mass, which suggested that highly polar and oligomeric compounds had been formed. Results from the toxicity testing were consistent with the hypothesis that the toxicity of the samples had been affected by changes in their composition (caused both by the atmospheric aging and by changes in the initial composition of the DE presumably associated with changes in the engine, which was new at the outset and accrued wear during the study). PMID- 20572367 TI - Current therapy for condyloma acuminata of the patients attending female STD Unit, Siriraj Hospital. AB - OBJECTIVE: To describe the treatment pattern of condyloma acuminata in female. MATERIAL AND METHOD: The 5-year medical records of 449 women treated for genital condyloma acuminata at the Gynecologic Infectious Diseases and Female Sexually Transmitted Disease (GID-FSTD) unit were reviewed. Data included the distribution of age, client by category, anatomical site and size, serologically coexisting sexually transmitted infection (STI), and treatment modalities. RESULTS: About half, 50.1%, of treatment was the application of topical trichloroacetic acid; followed by podophylline in the proportion of 35.5%. While the electric cauterization and imiquimod applications were uncommon therapy. Two-fifth ofthe subjects, 40.7%, was completely cured, and the remaining cases required additional management. CONCLUSION: The present setting, the wide range of treatment available is reflection of the fact that there is no ideal management. PMID- 20572369 TI - Prevalence of metabolic syndrome in reproductive-aged polycystic ovary syndrome Thai women. AB - OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in reproductive aged polycystic ovary syndrome (PCOS) Thai women. MATERIAL AND METHOD: A Cross sectional study was done at the Gynecologic Endocrinology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital of 250 PCOS Thai women who were diagnosed using Revised Rotterdam 2003 criteria, and who did not take medications affecting sex hormones or lipid metabolism, and attended the Gynecologic Endocrinology Unit between May 2007 and January 2009. Patents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood sample of each patient was drawn after 12-hour fasting. Prevalence of MS determined using the definitions of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), International Diabetes Federation (IDF), and National Heart Lung and Blood Institutes/American Heart Association (NHLBI/AHA). RESULTS: Mean +/- SD of age, body mass index (BMI), and waist circumference (WC) were 25.4 +/- 5.8 years, 26.2 +/- 7.6 kg/M2, and 82.3 +/- 16.3 cm, respectively. Prevalence of MS by the definitions of NCEP ATP III, IDF and NHLBI/AHA was 18.0%, 21.2%, and 21.2%, respectively. Of non-MS women, > 40% already had one to two criteria of IDF definition. Among MS women, 100% had central obesity, 50.9% had high blood pressure, 28.3% had impaired fasting blood glucose, 62.3% had hypertriglyceridemia, and 92.5% had high-density lipoprotein cholesterol < 50 mg/dL. The prevalence of MS increased from 10.3% in women aged < 20 years to 50.0% in those aged > or = 40 years (p of trend = 0.003), and from 0.0% in women with BMI < 23 kg/M2 to 54.5% in those with BMI > or = 30 kg/M2 (p of trend < 0.001). CONCLUSION: The prevalence of MS in reproductive-aged PCOS Thai women was 18.0% by NCEP ATP III and 21.2% by IDF and NHLBI/AHA. The prevalence varies only little with definitions of diagnostic criteria. The prevalence increases with age and body mass index. Slightly more than 40% of the non-MS PCOS Thai women already had one to two criteria of MS. PMID- 20572368 TI - Effectiveness of hormone therapy for treating dry eye syndrome in postmenopausal women: a randomized trial. AB - BACKGROUND: The efficacy of hormone therapy (HT) on dry eye syndrome remains debatable. OBJECTIVE: To study the efficacy of HT on dry eye syndrome. MATERIAL AND METHOD: A randomized controlled, double blind, parallel group, community based study in 42 post-menopausal patients was conducted. The patients had dry eye syndrome and were not taking any medications. They were assigned to one of two groups. Group A comprised 21 patients given transdermal 17 beta-estradiol (50 mg/day) and medroxy progesterone acetate (2.5 mg/day) continuously for three months and group B comprised 21 patients given both transdermal and oral placebo. Participants in the study were included for final analysis. The improvement of dry eye symptoms were measured by visual analog scale, tear secretion, intraocular pressure, corneal thickness, and tear breakup time determined before treatment and at 6 and 12 weeks of treatment. RESULTS: At 12 weeks, the number of patients who reported improvement of dry eye symptoms was greater in the HT group than that in the placebo group. However, the difference was not statistically significant (RR 0.25, 95% CI 0.04-2.80 and 0.60, 95% CI 0.33-2.03 in right and left eye, respectively). For other parameters, there was no significant difference between the two groups. CONCLUSION: According to the present study, there is no strong evidence to support the use of HT for treating dry eye syndrome. The limited number of participants included in the present study may have contributed to the insignificant effects. PMID- 20572370 TI - Risk factors of preeclampsia in Thai women. AB - OBJECTIVE: To determine the risk factors of preeclampsia in a university hospital. MATERIAL AND METHOD: The authors conducted a case control study involving 309 Thai pregnant women with preeclampsia and 309 controls who delivered at King Chulalongkorn Memorial Hospital, Bangkok, Thailand between June 2008 and May 2009. Information was taken from maternal inquiry, delivery records and antenatal care records. RESULTS: The risk factors that were significantly associated with increased risk of preeclampsia were maternal age > or = 35 years (ORs 1.7; 95% CI 1.1-2.9), nulliparity (ORs 3.8; 95% CI 2.5-5.7), prepregnancy body mass index > or = 30 kg/m2 (ORs 3.0; 95% CI 1.4-6.3), multifetal pregnancy (ORs 2.8; 95% CI 1.2-7.1), history of preeclampsia in a previous pregnancy (ORs 17.0; 95% CI 3.3-87.6) and chronic hypertension (ORs 19.5; 95% CI 2.4-155.7). Maternal age < 20 years (ORs 0.4, 95% CI 0.2-0.9) and prepregnancy body mass index < 20 kg/m2 (ORs 0.4; 95% CI 0.2-0.6) were significant protective factors against the development of preeclampsia. CONCLUSION: Risk factors of preeclampsia were maternal age > or = 35 years, nulliparity, prepregnancy body mass index > or = 30 kg/m2, multifetal pregnancy, history of preeclampsia in previous pregnancy and chronic hypertension. On the other hand, maternal age < 20 years and prepregnancy body mass index < 20 kg/m2 were significant protective factors against the development of preeclampsia. These risk factors should be of value to obstetricians counseling women regarding preeclampsia. PMID- 20572371 TI - Vaginal atrophy and sexual dysfunction in current users of systemic postmenopausal hormone therapy. AB - OBJECTIVE: To determine the prevalence of vaginal atrophy and sexual dysfunction in current users of systemic postmenopausal hormone therapy (pHT). MATERIAL AND METHOD: A cross-sectional study was conducted in 97 current users of pHT at Siriraj Menopause Clinic from 2005 to 2007. Subjective symptoms of vaginal atrophy and sexual dysfunction were assessed by interviewing. Objective signs of vaginal atrophy were assessed using pelvic examination, vaginal pH, and maturation value (MV). RESULTS: The prevalence of vaginal atrophy in current users of systemic pHT determining from patient's symptoms, pelvic examination, vaginal pH, and MV were 44.3%, 15.5%, 21.6% and 8.8%, respectively. The prevalence of sexual dysfunction varied from 48.7% to 71.6% depending on types of dysfunction. There was poor association between the subjective symptoms and signs, and the objective indicators of vaginal atrophy. Among various regimens of pHT, tibolone had the lowest prevalence of subjective atrophic symptoms; estrogen only pHT had the lowest prevalence of objective atrophic signs; and raloxifene had the highest prevalence of atrophic symptoms and signs, and sexual dysfunction. There was statistically significant association between regimens of pHT and objective indicators for vaginal atrophy (p = 0.004 for pH, and 0.000 for MV). CONCLUSION: Current users of systemic pHT still have vaginal atrophy and sexual dysfunction which relates to regimens of pHT. The prevalence of vaginal atrophy varies depending on the assessment methods. The subjective method gives higher prevalence than the objective one does. Since the subjective symptoms of vaginal atrophy would have more adverse effect on quality of life than the objective signs do, the authors suggest that patients' complaints be used to assess factors affecting vaginal atrophy in further research. PMID- 20572372 TI - Women in a region with high incidence of cervical cancer warrant immediate colposcopy for atypical squamous cells of undetermined significance on cervical cytology. AB - OBJECTIVE: To evaluate the histopathology of women who had "atypical squamous cells of undetermined significance" (ASC-US) on cervical cytology in a region with high incidence of cervical cancer. MATERIAL AND METHOD: Retrospective case record review of 254 women with ASC-US cytology undergoing colposcopic examination at Nakornping Hospital between October 2003 and September 2007. RESULTS: Of the 254 patients who had ASC-US smears underwent colposcopic and histopathologic evaluation. The mean age was 45.3 years (range, 18-72 years). The histologic diagnoses, obtained from colposcopically directed biopsy or endocervical curettage or loop electrosurgical excision procedure or cold knife conization after initial colposcopy, showed that 47 (18.5%) women had histologically confirmed high-grade lesions and 20 (7.9%) women had invasive cancers. There was no statistically significant difference in the incidence of high-grade or invasive lesions between who were 50 years old or more and those who were younger (50.0% and 50.5%, respectively, p = 0.39). CONCLUSION: Reporting ASC-US cytology in our population is obviously associated with significant cervical pathology, particularly invasive cancer that is possible at a rate higher than previously reported. Women who have ASC-US smears should therefore be referred for immediate colposcopy regardless of age. PMID- 20572373 TI - Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. AB - BACKGROUND AND OBJECTIVE: Although diabetes mellitus (DM) patients are claimed to be under oxidative stress because of prolonged exposure to hyperglycemia, the influence of glycemic control and cardiovascular complication in diabetes on oxidative stress parameters has not been fully studied. The present study aimed to investigate lipid peroxidation end product (malondialdehyde, MDA) and antioxidant enzymes in fairly controlled type 2 DM (fasting plasma glucose [FPG] < or = 180 mg/dl) or type 2 DM complicated with coronary heart disease (CHD) and poorly controlled type 2 DM (FPG > 180 mg/dl) in comparison to a normal healthy group (FPG < 110 mg/dl). MATERIAL AND METHOD: MDA and antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were determined in the red cell of 19 subjects with poorly controlled type 2 DM, 26 subjects with fairly controlled type 2 DM and 20 subjects with type 2 DM complicated with CHD who were matched for age and gender. Twenty healthy subjects with normal plasma glucose level and matched for age and gender were served as a control group. In all groups of DM these oxidative stress parameters were compared to a control group by one-way ANOVA test. Pearson rank correlation coefficient was used to compare the relationship between FPG and oxidative stress status in type 2 DM and normal controls. RESULTS: The red cell MDA levels were significantly higher in all types of diabetes compared to age-matched normal controls. The mean of red cell MDA level was highest in type 2 DM complicated with CHD. Red cell antioxidant enzyme activities were also significantly increased except for SOD and GPx activities in fairly controlled type 2 DM. The significant positive correlation between oxidative stress status (as MDA and CAT) and FPG was found in poorly controlled type 2 DM and type 2 DM complicated with CHD whereas in fairly controlled type 2 DM the significant positive correlation between CAT and FPG was only observed. CONCLUSION: These findings strongly confirmed the evidence that diabetic patients were susceptible to oxidative stress and higher blood glucose level had an association with free radical mediated lipid peroxidation. The highest level of MDA in type 2 DM complicated with CHD suggested that oxidative stress played an important role in the pathogenesis of cardiovascular complication. The results also showed the increase in antioxidant enzymes. These could probably be due to adaptive response to pro oxidant in diabetic state. Hence, there seems to be imbalance between oxidant and antioxidant systems in type 2 diabetic patients. PMID- 20572374 TI - Comparative study between chitin/polyacrylic acid (PAA) dressing, lipido-colloid absorbent dressing and alginate wound dressing: a pilot study in the treatment of partial-thickness wound. AB - BACKGROUND: Polyacrylic acid grafted chitin (Chitin-PAA) contains a hydrogel characteristic that makes it more suitable for wound dressing application. In animal models, Chitin-PAA dressing exhibited properties as a promising dressing. Epithelization promotion, rapid reduction of wound size, reduction of inflammatory cell response, and less toxicity had been noted. OBJECTIVE: Carryout a pilot clinical comparative study of Chitin-PAA dressing, lipido-colloid absorbent dressing, and alginate wound dressing in the treatment of partial thickness wound. MATERIAL AND METHOD: Between June 2006 and March 2007, 36 partial-thickness wounds were randomized into three groups and three different types of dressing were used. Each wound was treated until it was completely healed, and a visual analogue scale was used for the pain evaluation. RESULT: The present study shows the visual analogue pain score in the Chitin-PAA group seems to be a bit higher than the Urgocell group but not statistically different. The completely healed day is not significantly different. Three patients in the lipido-colloid absorbent dressing groups had wound infection but eventually healed after treatment. CONCLUSION: There was no statistical difference in terms of visual analogue pain score and healing time between the lipido-colloid absorbent dressing, alginate dressing, and chitin-PAA dressing. PMID- 20572375 TI - The Thai Anesthesia Incident Monitoring Study (Thai AIMS): an analysis of perioperative complication in geriatric patients. AB - BACKGROUND: The present study was a part of the multi-centered study of model of Anesthesia related adverse events in Thailand by incident report. (The Thai Anesthesia Incident Monitoring Study or Thai AIMS). The objective of the present study was to identify and analyze anesthesia incident in geriatric patients in order to find out the frequency distribution, clinical courses, management of incidents and investigation of model appropriate for possible corrective strategies. MATERIAL AND METHOD: This study was a prospective descriptive multicentered study conducted between January 1, 2007 and June 30, 2007. Incident reports from 51 hospital across Thailand were sent to data management unit on anonymous and voluntary basis. The authors extracted relevant data from the incident reports on geriatric patients (age 65 or more). The cases were reviewed by 3 anesthesiologists. Any disagreement was discussed and judged to achieve a consensus. Descriptive statistics was used. RESULTS: Among 407 incident reports and 559 incidents, there were more male (52.8%) than female (46.7%) patients with ASA PS 2, 3, 4 and 5 = 38.6%, 42.8%, 14.5% and 4.2% respectively. Surgical specialties that posed high risk of incidents were general, orthopedic, neurological, urologic and otorhiolaryngological surgery. Common places where incidents occurred were operating room (57.1%), ward (30.9%) and recovery room (12.0%). Common occurred incidents were arrhythmia needing treatment (30.0%), death within 24 hr (24.6%), desaturation (21.9%), cardiac arrest (16.2%) and reintubation (16.0%). The causes of the incidents were mostly attributed from patients underlying diseases and conditions. Most common outcomes were major physiologic changes with 26.5% fatal outcome at 7 days. The most common contributing factor was human factor (inappropriate decision and inexperience). Vigilance and having more experience could be the minimizing factors. CONCLUSION: Incidents in geriatric patients were similar to all age group patients with a higher incidents in death within 24 hr. The outcome were more serious resulting in 26.5% fatal outcome at 7 days. Quality assurance activity, clinical practice guidelines and improved supervision were suggested corrective strategies. PMID- 20572376 TI - Risk factors for retinal breaks in patients with symptom of floaters. AB - OBJECTIVE: To identify the risk factors of retinal breaks in patients with the symptom of floaters, and to determine the association between those risk factors and retinal breaks. MATERIAL AND METHOD: A retrospective analytic study of 184 patients (55 males and 129 females) that included 220 eyes was conducted. Patient information such as age, symptoms (multiple floaters, flashing), duration of symptom, refractive error, history of cataract surgery, family history of retinal detachment, and complete eye examination were recorded. The patients were divided into two groups, the first group (control group) had symptoms of floaters and no retinal breaks, the second group (retinal breaks group) had symptoms of floaters with retinal breaks. Chi-square test, and the multiple logistic regression were used for statistical analysis. RESULTS: Two hundred twenty eyes, 175 eyes of the control group and 45 eyes of the retinal breaks group were examined and included in this study. The multiple logistic regression analysis revealed that patients with multiple floaters, and floaters and flashing increased the risk of retinal breaks to 5.8 and 4.3 times, respectively, when compared to patients with single floater or floaters alone. Lattice degeneration increased the risk of retinal breaks to 5.9 times when compared to eyes that did not have lattice degeneration. CONCLUSION: Multiple floaters, flashing and lattice degeneration are risk factors of retinal breaks in patients with symptoms of floaters. Therefore, it is important for the ophthalmologists to be aware of these risk factors and the patients at risk should have follow-up examinations. PMID- 20572377 TI - Prevalence and associated factors of musculoskeletal pain among the dental personnel in a dental school. AB - OBJECTIVE: To study the prevalence and associated factors of musculoskeletal (MS) pain among the dental personnel. In addition, impacts and treatment of MS pain were reported. MATERIAL AND METHOD: Random sampling of 390 participants from the name lists of dental personnel working in each department. Self-administered questionnaires were equally distributed to three groups of dental personnel namely clinical instructors, postgraduate students, and dental assistants. The present study was conducted as a survey in the Faculty of Dentistry, Mahidol University, Bangkok between December 2008 and January 2009. RESULTS: Three hundred and ninety questionnaires were delivered and 164 questionnaires were returned (response rate 42.5%). The participants with MS pain were 32 clinical instructors (20.3%), 52 postgraduate students (32.9%), and 74 dental assistants (46.8%). Their mean age was 33.0 +/- 9.1 years old. The MS pain found respectively was shoulder pain 72.2% (n = 114), neckpain 70.3% (n = 111), and low backpain 50.6% (n = 80). The participants with shoulder and neckpain were combined and defined as cervicobrachial pain. The associated factor of cervicobrachial pain was working status. Being a clinical instructor and postgraduate student were associated with cervicobrachial pain with OR being 4.7 [1.3, 7.1] and 4.6 [1.6, 13.4], respectively. The impacts of MS pain among the dental personnel included usage of pain relieving medication (34.8%), seeking medical evaluation (32.3%), reduction in working hours (27.2%), difficulty sleeping (22.8%), and work absence (10.8%), respectively. The treatments of MS pain utilized to alleviate those impacts were Thai traditional massage (51.9%), medication (28.5%), physical therapy (15.8%), acupuncture (7.6%), and alternative medicine (4.4%), respectively. CONCLUSION: Cervicobrachial pain was the most prevalent MS pain among the dental personnel and working status was associated with their MS pain problems. The impact of MS pain was predominantly usage of pain relieving medication. Thai traditional massage was the most utilized treatment. PMID- 20572378 TI - Pharmacokinetic and bioequivalence study of an oral 8 mg dose of rosiglitazone tablets in Thai healthy volunteers. AB - BACKGROUND: Rosiglitazone maleate is an antihyperglycemic agent in the thiazolidinedione class. It is indicated for the treatment of patients with type 2 diabetes mellitus. A new product of rosiglitazone has been developed. The pharmacokinetic in Thai subjects should be considered and the bioequivalent data of new generic product is required in order to assure the quality and performance. OBJECTIVE: To characterize the pharmacokinetics of rosiglitazone in Thai subjects and compare the bioequivalence of generic product of a single oral 8 mg rosiglitazone tablet with the innovator's product. MATERIAL AND METHOD: The present study was performed in 24 healthy Thai male volunteers. Each received a single oral dose of 8 mg rosiglitazone tablet. Double blind randomized two-way crossover design was used with two weeks washout period between treatments. After drug administration, a serial blood sample was collected over a period of 48 hours. Rosiglitazone plasma level was determined by HPLC with fluorescence detector. The pharmacokinetic parameters were determined by non compartment model. For bioequivalence determination, the difference of Cmax, AUC(0-t) and AUC(0-inf) were analyzed by ANOVA and 90% confidence interval. RESULTS: The mean +/- SD of pharmacokinetic parameters of generic product and the innovator's product were 0.82 +/- 0.52 vs. 1.02 +/- 1.50 hr of Tmax, 796.51 +/- 155.19 vs. 723.48 +/- 134.69 ng/ml of Cmax, 3.94 +/- 0.80 vs. 3.87 +/- 0.77 hr of T1/2, 4,308.43 +/- 1,006.28 vs. 4,135.66 +/- 1,061.96 ng x hr/ml of AUC(0-t), 4,384.65 +/- 1,035.15 vs. 4,183.87 +/- 1,075.39 ng x hr/ml of AUC(0-inf), respectively. The 90% confidence interval of mean difference of Cmax, AUC(0-t) and AUC(0-inf) (log transformed data) of generic product compared to the innovator's product were 98.42-122.18%, 97.28-109.66% and 97.79-110.30%, respectively. They were within the range of the acceptance criteria 80-125%. CONCLUSION: Pharmacokinetic parameters of a single oral dose of 8 mg rosiglitazone tablet were characterized in Thai healthy subjects. These parameters showed that rosiglitazone was rapidly absorbed with a short elimination half-life. The two formulations of rosiglitazone were bioequivalent. PMID- 20572379 TI - Quetiapine for primary insomnia: a double blind, randomized controlled trial. AB - OBJECTIVE: To evaluate the clinical efficacy of Quetiapine 25 mg for the treatment of primary insomnia. MATERIAL AND METHOD: A randomized, double-blind, placebo-controlled clinical trial was conducted. Patients with DSM-IV-TR defined primary insomnia were asked to record a sleep diary one week prior to treatment, followed by 2 weeks of nightly treatment with either Quetiapine 25 mg or placebo. The primary outcomes were total sleep time (TST), sleep latency (SL), daytime alertness and functioning and sleep satisfaction; side effects were recorded as secondary outcome. Data were collected between January 2007 and December 2007, at Srinagarind Hospital of Khon Kaen University. RESULTS: Thirteen patients completed the present study (mean age 45.95 years old; range 25-62). Quetiapine group increased mean TST by 124.92 minutes and 72.24 minutes in the placebo group. Mean SL was reduced by 96.16 minutes in the Quetiapine group and 23.72 minutes in the placebo group. Statistical significance was not reached between both groups. In the Quetiapine group two patients reported side effects of dry lips, dry tongue and morning drowsiness. CONCLUSION: The present study is the first study to evaluate the effect of Quetiapine in primary insomnia in a randomized controlled trial. Quetiapine at 25 mg at night did show a trend for improvement of TST and reduced SL in primary insomnia with few side effects but not reaching statistical significance. A study with a larger sample size is needed to demonstrate its efficacy. PMID- 20572381 TI - Successful treatment in superior mesenteric artery embolism: a case report and literature review. AB - The authors report a successful management of acute superior mesenteric artery embolism in a patient during the treatment of popliteal artery embolism. The diagnosis of this disease was confirmed by computerized tomographic angiography. Immediate surgical embolectomy and bowel resection were performed and postoperatively, he made an uneventful recovery except for minimal watery diarrhea for one week. In the present report the authors also review the in patient records at Siriraj Hospital during 2005-2009 consisting of 14 cases with the claim diagnosis of this condition. Most of the patients developed peritonism on abdominal examinations showing a delay in diagnosis. The mortality rate was 86% (12 cases) which was higher than international reports. It is important to note that patients presenting with abdominal pain with underlying risk factors of arterial embolism is the clue in early diagnosis of this condition. CTA mesenteric artery is the most appropriate investigation to visualize the presence of embolism. Finally, immediate revascularization treatment is essential in the successful management of this fatal vascular problem. PMID- 20572380 TI - Septicemia of unknown origin causing by Streptococcus agalactiae primary psoas abscess: a case report. AB - Staphylococcus aureus is the commonest organism resulting in primary psoas abscesses. However non-staphylococcal primary psoas abscesses have increasingly been published in the literature. Here, the author reports a case of primary psoas abscess in a type II diabetic woman previously diagnosed Streptococcus agalactiae septicemia of unknown origin, which rapidly responded to penicillin plus clindamycin and prompt surgical drainage. Diabetic patients are not only susceptible to soft tissue infection but also primary psoas abscess caused by Streptococcus agalactiae. PMID- 20572382 TI - Persistent hyperinsulinemic hypoglycemia of infancy associated with congenital neuroblastoma: a case report. AB - The authors report a rare case of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) with congenital neuroblastoma without feature(s) of Beckwith Wiedemann syndrome. A term newborn with a birth weight of 3,900 g developed hypoglycemia one hour after birth and required up to 20 mg/kg/min of intravenous glucose infusion to maintain euglycemia. Investigations during the critical period revealed an inappropriately high insulin level. An abdominal CT scan revealed a normal pancreas, right suprarenal mass, and liver nodules. A condition of stage 4S neuroblastoma was suspected and supported by an increased ratio of urine vanillylmandelic acid to creatinine. The bone marrow smear was normal. She underwent near total pancreatectomy at the age of 2 months. The suprarenal mass and liver nodules were not found during the operation or during repeated abdominal CT scans at 3 month of age. Spontaneous regression of neuroblastoma was suspected. The pathology of the pancreas was compatible with PHHI. PMID- 20572383 TI - Evidence of vascular compromise over the visual cortex during migrainous headache: a case report with MRI study. AB - The objective of the present study was to demonstrate MRI evidence of vascular compromise as seen in a 17-year-old female presenting with migrainous headache. The patient had been experiencing migrainous headache 2 days ago. She had visual auras lasting for a few hours before the attack. Upon meeting with her physician she indicated symptoms of left sided numbness during the headache. No neurological deficit was detected when the first MRI was performed, and all of her symptoms resolved within 4 days of the attack. The MRI study showed a focal area of restricted diffusion at the right visual cortex. A short segment of vascular enhancement was noted on the surface of the affected gyrus. MRS showed a normal N-acetyl aspartate, choline, and creatine with no elevation of lactate. A follow-up MRI study 5 months later showed normal finding with no residual lesion. The authors concluded that the abnormality on the first MRI was the ischemic insult of the ictal visual cortex which was transient during the migraine attack. The pathophysiology was more likely from reversible focal venous congestion. PMID- 20572384 TI - Photo-aging: a literature review. AB - The average age of people has been increasing over the years, triggering more awareness and more interest in the study of regenerative medicine, especially degeneration of the skin which is an organ that is crucial noticeably for appearance. Skin aging is the multifactorial process both internal and external factors, such as, age, sex, race, disease of internal organs and environmental exposure. However, the main causes of skin degeneration are heredity and sunlight. The latter induces the most skin degeneration. Due to strong sunlight all year round in the tropical zone, serious skin degeneration has an effect on Thai people, causing both anatomical change and microscopic change. Thus far, many studies have been conducted on pathogenesis and prevention of Photo-aging, as well as regeneration of damaged skin. The current article helps make further progress to these issues. PMID- 20572385 TI - [Calcium-binding Iba-1/AIF-1 protein in rat brain cells]. AB - At present, calcium-binding Iba-1 protein is considered to be identical to AIF-1 protein and it is used as one of the selective microglia markers. However, the data on the cell populations capable of expressing Iba-1/AIF-1, are inconsistent. The aims of the present study were to identify rat brain cells expressing Iba-1 and to define their structural characteristics. The methods of immunocytochemistry and confocal laser microscopy were used. Iba-1 protein was detected only in microglial cells, macrophages of brain meninges, supraependymal macrophages, superficial and stromal cells of the choroid plexus--all the cells possessing phagocytotic function. Comparison of the data obtained with the results of other studies allows to suggest that not all of commonly used antibodies against Iba-1/AIF-1 demonstrate the same product. It can not be excluded, that it can be associated with the presence of alternative splicing of Iba-1 mRNA. PMID- 20572386 TI - [The striopallidal projections of the zona incerta in the dog diencephalon]. AB - The projections of individual sectors of the zona incerta (ZI) in dog diencephalon to the functionally different striatal segments were studied by the method of the antero- and retrograde axonal transport of horseradish peroxidase. The data on the interconnections of ZI with all striopallidal structures, obtained by the author before and in the present work were summarized. Among all the striatal nuclei, the the rostral, ventral and caudal ZI sectors contained the neurons that projected their fibers only to the dorsal segments of the putamen. Not a single striatal structure was found to form projections to ZI. ZI and the dorsal pallidal nuclei (globus pallidus, nucleus entopeduncularis) are reciprocally connected with almost all ZI sectors. The connections of the ventral pallidum with the ZI were not detected. PMID- 20572387 TI - [NADPH-diaphorase-positive structures in the spinal cord and spinal ganglia]. AB - Using the histochemical reaction with the various incubation medium pH, the localization of NADPH-diaphorase was studied in the spinal cord and spinal ganglia of the adult rat. The data obtained indicate, that the application of the incubation medium with pH 7.4 allows to demonstrate the neurons with various NADPH-diaphorase activity, to define not only the density of enzyme distribution, but also to calculate the numbers of NADPH-diaphorase-positive neurons. It was established, that both in the spinal cord and spinal ganglia, NADPH-diaphorase activity was found not in all the neurons: high activity was found in small and medium neurons of the spinal ganglia, while low activity was detected in motoneurons. Other cellular structures of the spinal cord also possessed NADPH diaphorase activity and were found to be the interneurons. PMID- 20572388 TI - [Transcriptional activity of nuclear factor kappa B (NFkappaB) in posttraumatic sensory neurons (histochemical study)]. AB - Nuclear factor kappa B (NFkappaB) is a ubiquitous nuclear transcription factor that regulates the expression of a number of genes involved in cell survival, immune and inflammatory processes. It has been hypothesized that after nerve injury, the release of specific cytokines may provide a stimulus for activation of the transcription factor NF-kappaB in adult dorsal root ganglia (DRG) neurons exerting the protective effect on the sensory neurons. However, the complexity of this transcription factor has led to some misleading conclusions about NF-kappaB signalling in injured DRG neurons. The goal of the present study is to find out whether NF-kappaB is involved in the transcriptional regulation of genes in adult primary sensory neurons after peripheral nerve transection. In this series of experiments, we used a transgenic line of NF-kappaB reporter mice in which activation of NF-kappaB drives the expression of the lac-z gene. We show that the expression of beta-galactasidase (beta-gal) is not detected in injured DRG neurons and contralateral neurons. However, a strong beta-gal expression was detected in the muscle at the injury site. It may reflect the repressive influence of additional signalling cascades on NF-kappaB activity in sensory neurons. PMID- 20572389 TI - [Morphological features of the rat stellate ganglion during early postnatal development]. AB - The aim of this work was to study the anatomical characteristics of the stellate ganglion (SG) and the morphometric characteristics of its neurons in rats of different age groups (newborn, 10-, 20-, 30-, 60- and 180-day-old) using anatomical and histological methods. The results obtained indicated that in rats since birth there were three variants of branch origin from the medial margin of SG. No differences were observed in these variants between right and left SG. The sizes of both SG and its neurons increased during the first two months of postnatal development. The density of neurons in SG sections decreased from the moment of birth until the six months of age. The number of SG neurons did not change significantly in the postnatal ontogenesis. Thus, SG in rats is anatomically formed by the moment of birth, while the sizes and morphometric characteristics of SG neurons become finally stabilized by the second month of age. PMID- 20572390 TI - [Structure of the retina of Pacific salmon fry in twilight illumination during the geomagnetic field changes]. AB - The retinomotor response of the masu salmon Oncorhynchus masou fry retina was studied under the conditions of mesopic (twilight) illumination after experimental geomagnetic field (GMF) compensation which was reached using the Helmholtz coils. In the control group, the retinomotor response of masu salmon fry to twilight illumination was usual: the nuclei of the neurosensory rod cells were located immediately above the external limiting layer, while the nuclei of the neurosensory cone cells were displaced closer to the pigment epithelium. After experimental GMF compensation, the masu salmon fry retina reaction was unusual: the neurosensory cone cell nuclei adhered to the external limiting membrane, while the nuclei of the neurosensory rod cells were displaced closer to the pigment epithelium layer. Double and central neurosensory cone cells occupied the position that was inadequate to normal reaction to twilight: the bodies of these cells were considerably elongated, and the external segments reached the pigment epithelium layer. Thus, in the experiment with GMF compensation, we have found the unusual structure of the retina, which only vaguely corresponded to a reaction to mesopic adaptation. The results suggest, that the visible light is not a unique variety of the electromagnetic field, that could be perceived by the fish retina. PMID- 20572391 TI - [Characteristics of the human cerebral arterial circle in skulls of various shape]. AB - The vessels of the circle of Willis of a brain of adult persons were studied by macro-microscopic preparation computer tomography (CT-angiography). It was demonstrated that in dolichocranes, the anterior-posterior dimension of the circle of Willis was greater, than in meso- and brachicranes. Classical structure of the circle of Willis was found in humans in 38-46% of the cases studied (most frequently in dolichocranes). The vessels of the circle of Willis were characterized by a structural variability that was associated with the shape of the skull: in the individuals with meso- and brachicranial skull shape, the various deviations from the classical structure of the arteries of the circle of Willis were most common in its posterior area, while in dolichocranes these were most frequently seen in the anterior area. In 30-40% of the cases studied, there was a combination of the structural variations of the blood vessels in both anterior and posterior areas of the circle of Willis (a combined form). PMID- 20572392 TI - [Morphological characteristics of the Wistar rat thymus in experimental intracerebral hemorrhage]. AB - The purpose of the present investigation was to study thymus structure in 108 Wistar rats possessing different prognostic resistance to an emotional stress under the conditions of experimentally modeled intracerebral hemorrhage. It was demonstrated that after the intracerebral hemorrhage, the thymus underwent changes that were associated with both the stereotyped response to stress and the development of an immune response against the damaged brain tissue: relative thymus mass and the cortico-medullary index were shown to decrease, while the volumetric fractions of the capsule and connective tissue septa were increased. The reaction of the vascular bed included stasis, diapedesis and perivascular edema. These changes were more expressed in the rats predisposed to an emotional stress. PMID- 20572393 TI - [Changes in duodenal lymphoid structures in rats with various behavioral activity, caused by delta sleep-inducing peptide and following acute emotional stress]. AB - The effect of delta sleep-inducing peptide (DSIP) on the lymphoid structures of small intestine, was investigated. Studies were conducted on 42 male Wistar rats, which were previously assessed in an "open field" test. According to the results of the test, rats were divided into behaviorally active animals (prognostically resistant to stress) and passive ones (resistant to the effects of stress). As a stress, immobilization of the animals in pens with an electrical stimulation of their back for 1 hour, was used. Intraperitoneal injection of DSIP resulted in a reduction of eosinophil number in rats of all the experimental groups. After DSIP injection to the active rats of the control group, the increase in small and medium lymphocyte numbers was detected that was more expressed than in the passive rats. After an acute exposure of behaviorally active rats to stress, the number of the cells of lymphoid series was increased,mainly due to the increase in small and medium lymphocytes. In the group of passive rats, stress exposure and DSIP injection resulted in the increase of plasma cell number in all the duodenal mucosa structures studied. PMID- 20572394 TI - [Changes in mast cell composition in the hamster duodenum in experimental diphyllobothriosis]. AB - The morphometric investigation was performed to study the reaction of mast cells (MC) in mucosal lamina propria of hamster duodenum to experimental infection with tapeworm Diphyllobothrium dendriticum. The invasion was found to result in a significant increase of MC cells absolute content, changes in the proportions of their functional groups, increased anaphylactic MC degranulation, enhanced MC precursor migration and their accelerated differentiation. PMID- 20572395 TI - [Reactive changes in the smooth muscle tissue of the rat small intestine during experimental intestinal obstruction]. AB - Using light, electron microscopy and immunohistochemical methods, the reactive transformation of smooth muscle tissue (SMT) was studied in the intestinal wall during the development of acute partial high intestinal obstruction. The material of small intestine was taken from 10 male rats in both the zone of ligature application, and proximal and distal zones, 3 cm distant from the ligation zone. The results of the study demonstrate that in partial intestinal obstruction, the nature of structural and functional SMT transformation was variable depending upon differences in functional and destructive loads. During these changes, the remodeling of smooth myocyte population was shown to be one of the mechanisms of SMT adaptation to the changing conditions of functioning. Immunohistochemical analysis found no changes in the pattern of expression of marker and phenotypic proteins in the intestinal zones studied during the dynamics of an experiment. PMID- 20572396 TI - [Analysis of the changes in the cellular populations of the pancreatic pseudocyst in an experiment]. AB - The purpose of the research was to study, using the quantitative methods, the cellular populations of neutrophilic granulocytes, macrophages, fibroblasts and lymphocytes in the connective tissue of the wall of the pancreatic pseudocyst. Local cold application to the pancreas of albino rat with the help of KCH 3A/B cryosurgical complex was used for the modeling of the pseudocyst. General decrease in the cell content in wall of the pseudocyst was detected together with the changes of predominant cell populations during the study. At days 14-21 of the experiment, the neutrophilic granulocytes were found to dominate, by day 30 the dominating cells were the macrophages, which were substituted by fibroblasts at day 45. The progressive increase of the number of lymphocytes was found throughout the the experiment. PMID- 20572397 TI - [Morphological parameters of the liver in rats during changes in nitric oxide content and deafferentation with capsaicin]. AB - The aim of this investigation was to study the morphological changes of rat liver during the blockade of nitric oxide (NO) synthesis and its increased content in the intact rats and after the damage of capsaicin-sensitive nerves. It was shown that the damage of capsaicin-sensitive nerves resulted in dystrophic and necrotic changes in the liver, associated with the inflammatory reaction. These changes were enhanced by the blockade of NO-synthase. NO deficiency, caused by NO synthase blockade, lead to disturbances of vascular bed control, resulting in ischemia and hypoxia, and, as a consequence, in dystrophic and necrotic changes in hepatocytes. The data obtained indicate that in the development of dystrophic changes after the modification of the function of capsaicin-sensitive nerves, along with the decrease in the sensory neuropeptide content, the significant role is played by NO-dependent machanisms. Administration of NO precursor, L-arginine, after deafferentation with capsaicin, inhibited the inflammatory reactions in the liver. PMID- 20572398 TI - [Sex hormones receptor expression and the activity of the argyrophilic proteins of the nucleolar organizer region in the intact myometrium cells and in uterine leiomyoma]. AB - The authors have analyzed the expression of progesterone receptor (PR) and estrogen receptor alpha (ER) in comparison with the argyrophil proteins content in the nucleolar organizer region (NOR) in 106 samples of the intact myometrium and in 106 tumourous nodes of the simple leiomyoma. PR expression was shown in 100% cases of the intact myometrium and simple leiomyoma, while ER expression was far less common, 37 +/- 4.2 and 23.5 +/- 4.1%, respectively. There were much fewer AgNOR proteins in the intact myometrium than in the leiomyoma (3.1 +/- 0.5 and 5.6 +/- 0.4, respectively). Moreover, the number of AgNOR proteins was shown to depend on the presence of ER: when smooth muscle cells were ER-positive, there were fewer argyrophilic granules than when they were absent in both intact myometrium and simple leiomyoma. PMID- 20572399 TI - [Analysis of the histoenzymatic activity in the sebaceous glands of the Kopetdag pine vole]. AB - This work presents the results of the semi-quantitative evaluation of histochemical phosphatase activity in the sebaceous glands of the Kopetdag pine vole (Microtus socialis paradoxus Ognev et Heptner, 1928). The studies included the conversion of standard histochemical designations of enzymatic activity into digital analogues, allowing to evaluate the level of enzymatic activity and sexual dimorphism. In male voles, the index of the acid phosphatase enzymatic activity was 16% higher in summer than in winter. This index in female voles was less in winter than in summer by 28%. The index of the alkaline phosphatase enzymatic activity in male voles in summer higher than in winter by 4%. Female voles had the same seasonal differences. Male voles had higher July adenosine triphosphatase activity indexes in comparison with December indexes, but in females this situation was the opposite--summer values of activity were 16% less than winter values. Sexual dimorphism of acid phosphatase activity was greater in summer than in winter. Index of sexual dimorphism of alkaline phosphatase activity was twice less in summer than in winter, but their actual values were small. Maximum sexual dimorphism was observed in adenosine triphosphatase activity of during summer period, and it was greatly reduced in winter (from 27.0 to 4.0%). PMID- 20572400 TI - [Use of computer technologies for studying the morphological characteristics of the iris color in anthropology]. AB - Digital images of the iris were received for study peculiarities of the iris color during the anthropological examination of 578 students aged 16-24 years. Simultaneously with the registration of the digital images, the visual assessment of the eye color was carried out using the traditional scale of Bunak, based on 12 ocular prostheses. Original software for automatic determination of the iris color based on 12 classes scale of Bunak was designed, and computer version of that scale was developed. The software proposed allows to conduct the determination of the iris color with high validity based on numerical evaluation; its application may reduce the bias due to subjective assessment and methodological divergences of the different researchers. The software designed for automatic determination of the iris color may help develop both theoretical and applied anthropology, it may be used in forensic and emergency medicine, sports medicine, medico-genetic counseling and professional selection. PMID- 20572402 TI - [Andrei L'vovich Polenov and domestic neuroendocrinology]. PMID- 20572401 TI - [Age dynamics of the human maxillofacial apparatus development in the early period of prenatal ontogenesis]. AB - The literature review discusses the debatable problems on terms of separation of different anlages of human maxillo-facial apparatus, chronology of histo- and organogenetic remodeling of hard and soft tissues during the period of their formation in the first trimester of pregnancy. It is suggested that these controversies are most likely determined by imperfection of current embryogenesis periodization systems and of criteria of human embryos and fetuses age definition; therefore further research in this direction is required. PMID- 20572403 TI - Effects of guided imagery on postoperative outcomes in patients undergoing same day surgical procedures: a randomized, single-blind study. AB - The purpose of this investigation was to evaluate the effects of guided imagery on postoperative outcomes in patients undergoing same-day surgical procedures. Forty-four adults scheduled for head and neck procedures were randomly assigned into 2 groups for this single-blind investigation. Anxiety and baseline pain levels were documented preoperatively. Both groups received 28 minutes of privacy, during which subjects in the experimental group listened to a guided imagery compact disk (CD), but control group patients received no intervention. Data were collected on pain and narcotic consumption at 1- and 2-hour postoperative intervals. In addition, discharge times from the postoperative anesthesia care unit (PACU) and the ambulatory procedure unit and patient satisfaction scores were collected. The change in anxiety levels decreased significantly in the guided imagery group (P = .002). At 2 hours, the guided imagery group reported significantly less pain (P = .041). In addition, length of stay in PACU in the guided imagery group was an average of 9 minutes less than in the control group (P = .055). The use of guided imagery in the ambulatory surgery setting can significantly reduce preoperative anxiety, which can result in less postoperative pain and earlier PACU discharge times. PMID- 20572404 TI - Combined spinal/general anesthesia with postoperative femoral nerve block for total knee replacement in a patient with familial hyperkalemic periodic paralysis: a case report. AB - Familial hyperkalemic periodic paralysis (HYPP) is a rare genetic disorder in which the sodium channels in skeletal muscle cells have altered structure and function. Small elevations in serum potassium lead to inactivation of sodium channels, causing episodic weakness or paralysis. Exposure to cold, anesthesia, fasting, emotional stress, potassium ingestion, and rest after exercise can stimulate an attack. This case report describes a 65-year-old man with HYPP who was admitted for a right total knee arthroplasty. He had a history of arteriosclerotic heart disease and stenting 8 years earlier, previous inferior wall myocardial infarction with ejection fraction of 65%, anxiety, degenerative joint disease, well-controlled type 2 diabetes mellitus, and a body mass index of 53.3 kg/m2. A combined spinal/general anesthetic with a femoral nerve block for postoperative pain control was chosen. Careful attention was given to monitoring and maintenance of core temperature, use of insulin and glucose to maintain normokalemia, and carbohydrate loading the night before surgery. The patient recovered from the anesthetic without complication and had pain relief for approximately 22 hours postoperatively because of the femoral nerve block. The patient was without weakness or paralysis related to HYPP in the postanesthesia care unit or throughout his hospitalization. PMID- 20572405 TI - Lumbar epidural catheter placement in the presence of low back tattoos: a review of the safety concerns. AB - Current fashion in body art includes low back tattoos of varying designs and colors, a trend that presents unique concerns for anesthesia providers. Does the placement of epidural catheters risk the introduction of tattoo pigment dyes into the epidural space through the process of coring? Are there specific risks associated with tattoo dyes and epidural needle placement? We performed a comprehensive review of the literature using multiple search databases with the intent to form guidelines for practice using a level of evidence taxonomy. The available evidence does not identify any specific risks associated with epidural catheter placement through low back tattoos, although tissue coring with tissue transport to deeper sites has been confirmed. Continued investigation is necessary before comprehensive practice guidelines regarding the practice of placing epidural needles and catheters through lumbar tattoos can be developed. We suggest avoidance of piercing tattoos when performing epidural punctures until there is sound evidence of short-term and long-term safety. PMID- 20572406 TI - Caudal anesthesia in a patient with severe pulmonary hypertension. AB - Delivery of anesthesia to patients with severe pulmonary hypertension can be extremely challenging. The profound hemodynamic alterations of the disease can often be exacerbated by alterations in circulatory function brought about by anesthetic and surgical interventions. High perioperative morbidity and mortality rates have been reported. Minimizing adverse outcomes in these patients requires careful perioperative evaluation and planning. Selection of an anesthetic technique suitable for the surgery without causing major hemodynamic alterations, which can lead to cardiac failure and death, is a unique consideration of the anesthesia provider. As shown in this case report, caudal anesthesia, when appropriate, can offer a safe anesthetic for these patients. PMID- 20572407 TI - Overview of complex regional pain syndrome and recent management using spinal cord stimulation. AB - Complex regional pain syndrome (CRPS) is an enigmatic disease process affecting the upper and lower extremities. It consists of various combinations of sensory, autonomic, and motor abnormalities, the pathogenesis of which is unclear. Formally known as reflex sympathetic dystrophy or causalgia, CRPS has a revised taxonomy since 1994. The International Association for the Study of Pain established 2 categories, type I and type II, based on precipitating events. This syndrome manifests in 3 progressive stages, displaying peripheral and central neurologic aberrancies. The exact triggering mechanism is unclear but appears to involve neurogenic inflammation from axonal damage to small-fiber distal nerves. Central sensitization independent of afferent input and central somatotopic reorganization may be contributory in successive stages. Treatment goals are twofold: management of pain and restoration of function. Time is critical, as therapeutic effectiveness is limited in the latter stage. Various treatment modalities, including medication regimens, sympathetic nerve blocks, and physical therapy have met with differing degrees of success. Recent advances in spinal cord stimulation are promising. Although initially costly, this may prove to be the least expensive and most effective treatment in the long-term. PMID- 20572408 TI - Patient outcomes comparing CRNA-administered peripheral nerve blocks and general anesthetics: a retrospective chart review in a US Army same-day surgery center. AB - We compared outcomes between patients receiving general anesthesia (GA) vs regional block (RB) in a military same-day surgery unit (SDSU), where Certified Registered Nurse Anesthetists (CRNAs) delivered all RBs and GA. All patient charts from 2003 through 2006 were reviewed. Patients were included if they were 18 years or older, had an ASA physical status I or II, and underwent a shoulder or knee arthroscopy that used either RB or GA. Overall, 342 patients met inclusion criteria: 161 GA and 181 RB. With GA, mean anesthesia time was shorter (109.6 vs 135.5 minutes, P < .001), but recovery times were longer (56.7 vs 36.4 minutes, P < .001). SDSU times were nearly identical (GA vs RB, 71.5 vs 72.8 minutes), resulting in a total hospital time that was not significantly different (352.7 vs 347.5). The GA group received more morphine equivalents of narcotic in the operating room (22.9 vs 15.1 mg, P < .001) yet still had higher pain scores postoperatively than the RB group (1.1 vs 0.3, P < .001). The GA group received a significantly greater number of antiemetic doses intraoperatively (0.58 vs 0.04, P < .001) but still had a higher, although nonsignificant, rate of emesis (15.5% vs 10.0%). Patients receiving RB had less pain and received less analgesia without any increase in postoperative nausea and vomiting, hospital time, or anesthesia-related complications. PMID- 20572409 TI - Case report: anesthetic management of acute fatty liver of pregnancy in the postpartum period. AB - Acute fatty liver of pregnancy (AFLP) is a potentially fatal metabolic disorder that manifests during the third trimester. Early diagnosis, termination of pregnancy, and treatment of complications associated with AFLP significantly reduce maternal morbidity and mortality. While most cases of AFLP occur before delivery, some may occur after vaginal delivery. Anesthesia providers should have a high level of suspicion for AFLP in a patient with altered mental status and elevated liver function test results in the postpartum period. Anesthetic implications include early recognition of liver dysfunction and aggressive resuscitation and treatment of hypoglycemia, disseminated intravascular coagulopathy, and other associated complications and reduction or avoidance of medications with substantial hepatic metabolism. This is a case report describing the management of a woman with AFLP in whom acute liver failure rapidly developed after a vaginal delivery with epidural analgesia at a small overseas hospital. PMID- 20572410 TI - Effects of arterial blood pressure on rebleeding using Celox and TraumaDEX in a porcine model of lethal femoral injury. AB - This study was designed to identify the systolic blood pressure (SBP) and mean arterial pressure (MAP) at which rebleeding occurs when a clot is formed by a hemostatic agent, Celox or TraumaDEX, compared with a standard dressing. Fifteen pigs (5 each) were assigned randomly to 1 of 3 groups: Celox, TraumaDEX, or standard pressure dressing as a control. In all animals, the femoral artery and vein were transected to simulate traumatic injury. Subjects were allowed to hemorrhage 1 minute before treatment. Direct pressure was held 5 minutes followed by application of elastic dressings for 30 minutes. Dressings were removed after 30 minutes, and the wound was observed for rebleeding. Animals demonstrating hemostasis received phenylephrine infusion to increase SBP in 10-mm Hg increments until SBP reached 210 mm Hg or hemorrhage recurred. There were statistically significant differences between Celox (mean SBP, 166.4 mm Hg; mean MAP, 1376 mm Hg) and the control (mean SBP, 88.25 mm Hg; mean MAP, 59.7 mm Hg), and between TraumaDEX (mean SBP, 152.2 mm Hg; mean MAP, 113.2 mm Hg) and the control (P < .05). However, no statistically significant difference existed between Celox and TraumaDEX. Celox and TraumaDEX effectively prevent rebleeding compared with standard dressing. PMID- 20572411 TI - Apoptosis: understanding programmed cell death for the CRNA. AB - Apoptosis, or programmed cell death, is a physiologic mechanism employed by most multicellular organisms to maintain homeostasis of body tissues. In balance with the production of new cells by mitosis, apoptosis provides for the orderly destruction and removal of cells that are no longer needed by the organism. Apoptosis occurs by complex pathways involving multiple biochemical signals and processes. Dysfunctional apoptotic mechanisms are the pathologic basis for many human diseases, including common disorders of the heart, lungs, brain, and endocrine systems. Researchers have demonstrated in animal models that neurodegenerative changes after the administration of anesthetic drugs are related to apoptosis. Anesthesia drugs have been found to induce apoptosis, perhaps through the production of reactive oxygen species. Propofol is a drug used in anesthesia that has unique antioxidant qualities that may be beneficial. The purpose of this article is to review, for nurse anesthesia providers, current information about the process of apoptosis, the role of apoptosis in comorbid diseases, and the implications of the effects of anesthesia drugs on normal apoptotic mechanisms that need to be evaluated as potential sources of risk or benefit to surgical patients. PMID- 20572412 TI - Cystic fibrosis: a systems review. AB - Cystic fibrosis (CF) is a fatal genetic disorder that affects many organ systems in the body. Historically, few patients with CF lived beyond early childhood, but with continuous improvement in treatment modalities, quality of life and the life span of persons with CF has greatly improved. As the surviving population of people with CF increases, a greater chance of encountering them in anesthesia practice exists. Comorbidities associated with the disease, such as diabetes mellitus and osteopenia, may also contribute to an increased frequency of surgical and anesthetic encounters. An understanding of the pathophysiology of the disease, as well as anesthetic implications and management, is crucial to the safe administration of anesthesia in this population. Cystic fibrosis is traditionally thought of as a childhood disease affecting the lungs and pancreas, which does not accurately describe the disease in its entirety. Many organ systems are affected, from the heart and lungs to the reproductive system, and may warrant alterations in an anesthetic plan. This review highlights the pathologic conditions associated with multiple systems, therapy regimens, and potential complications and suggests anesthetic implications. PMID- 20572414 TI - The pursuit of happiness: sleep apnea, sex, and sleepiness. PMID- 20572413 TI - Outcome of CPAP treatment on intimate and sexual relationships in men with obstructive sleep apnea. AB - STUDY OBJECTIVES: To examine intimate and sexual relationships in patients with obstructive sleep apnea (OSA), the association with daytime sleepiness, and the change in these outcomes with continuous positive airway pressure treatment (CPAP). DESIGN: Pre-post test, quasi-experimental study. SETTING: Seven sleep disorders centers in the U.S. and Canada. PARTICIPANTS: 123 males with OSA (AHI > or =20), aged 21 to 60 years. INTERVENTIONS: Nasal CPAP for > or =3 months. MEASUREMENTS AND RESULTS: Compared to normal values, at baseline patients were significantly sleepier, as measured by the Multiple Sleep Latency Test and Epworth Sleepiness Scale. They were also more impaired in intimate and sexual relationships, as measured by the Intimate and Sexual Relationships subscale of the Functional Outcomes of Sleep Questionnaire. Neither race nor marital status was significantly associated with impaired intimate and sexual relationships. Following treatment, patients were significantly more alert and had reported improved intimate and sexual relationships, with the greatest change occurring in those with the most disease severity. CONCLUSIONS: OSA has an adverse impact on intimate and sexual relationships that is related to subjective sleepiness and improved with CPAP treatment. PMID- 20572415 TI - Cues to starting CPAP in obstructive sleep apnea: development and validation of the cues to CPAP Use Questionnaire. AB - BACKGROUND: The reasons that a patient has to start treatment, their "Cues to Action", are important for determining subsequent health behaviors. Cues to action are an explicit component of the Health Belief Model of continuous positive airway pressure (CPAP) acceptance. At present, there is no scale available to measure this construct for individuals with obstructive sleep apnea (OSA). This paper aims to develop, validate, and describe responding patterns within a sample of patients with OSA to the Cues to CPAP Use Questionnaire (CCUQ). METHOD: Participants were 63 adult patients diagnosed with OSA who had never tried CPAP when initially recruited. The CCUQ was completed at 1 month after being prescribed CPAP. RESULTS: Exploratory factor analysis (EFA) showed a 3-factor structure of the 9-item CCUQ, with "Health Cues", "Partner Cues", and "Health Professional Cues" subscales accounting for 59.91% of the total variance. The CCUQ demonstrated modest internal consistency and split-half reliability. The questionnaire is brief and user friendly, with readability at a seventh-grade level. The most frequently endorsed cues for starting CPAP were Health Professional Cues (prompting by the sleep physician) and Health Cues such as tiredness and concern about health outcomes. CONCLUSIONS: This study validates a measure of an important motivational component of the Health Belief Model. Health Professional Cues and internal Health Cues were reported to be the most important prompts to commence CPAP by this patient sample. PMID- 20572416 TI - Comparison of positional therapy to CPAP in patients with positional obstructive sleep apnea. AB - STUDY OBJECTIVES: We hypothesized that positional therapy would be equivalent to continuous positive airway pressure (CPAP) at normalizing the apnea-hypopnea index (AHI) in patients with positional obstructive sleep apnea (OSA). METHODS: Thirty-eight patients (25 men, 49 +/- 12 years of age, body mass index 31 +/- 5 kg/m2) with positional OSA (nonsupine AHI <5 events/h) identified on a baseline polysomnogram were studied. Patients were randomly assigned to a night with a positional device (PD) and a night on CPAP (10 +/- 3 cm H2O). RESULTS: Positional therapy was equivalent to CPAP at normalizing the AHI to less than 5 events per hour (92% and 97%, respectively [p = 0.16]). The AHI decreased from a median of 11 events per hour (interquartile range 9-15, range 6-26) to 2 (1-4, 0-8) and 0 events per hour (0-2, 0-7) with the PD and CPAP, respectively; the difference between treatments was significant (p < 0.001). The percentage of total sleep time in the supine position decreased from 40% (23%-67%, 7%-82%) to 0% (0%-0%, 0% 27%) with the PD (p < 0.001) but was unchanged with CPAP (51% [36%-69%, 0% 100%]). The lowest SaO2 increased with the PD and CPAP therapy, from 85% (83% 89%, 76%-93%) to 89% (86%-9%1, 78%-95%) and 89% (87%-91%, 81%-95%), respectively (p < 0.001). The total sleep time was unchanged with the PD, but decreased with CPAP, from 338 (303-374, 159-449) minutes to 334 (287-366, 194-397) and 319 (266 343, 170-386) minutes, respectively (p = 0.02). Sleep efficiency, spontaneous arousal index, and sleep architecture were unchanged with both therapies. CONCLUSION: Positional therapy is equivalent to CPAP at normalizing the AHI in patients with positional OSA, with similar effects on sleep quality and nocturnal oxygenation. PMID- 20572417 TI - Impact of gender on incident diabetes mellitus in obstructive sleep apnea: a 16 year follow-up. AB - STUDY OBJECTIVE: To address the influence of gender and obstructive sleep apnea (OSA) on development of diabetes mellitus (DM) in a sleep clinic cohort. DESIGN: A longitudinal observational study. PARTICIPANTS: A consecutive middle-aged (30 69 years) sleep clinic cohort from 1991 (n=318; 254 men, 64 women) with eligible baseline characteristics, clinical charts, and information from the Swedish Hospital Discharge Registry were identified. Ten individuals with DM at baseline and 47 patients who died during the follow-up period were excluded. MEASUREMENTS: The remaining 261 subjects were asked to complete a postal questionnaire regarding concomitant diseases including DM, diagnosed by a physician. RESULTS: In total, 168 patients (64.4%) replied. The incidence of DM was 24.9% in patients with OSA (overnight oxygen desaturations > or =30 in 1991) compared with 10.8% in subjects without OSA (p = 0.020). New-onset DM in men was 19.1% in OSA vs. 11.1% in non-OSA (n.s.), while the corresponding values in women were 50.0% in OSA and 9.5% in non-OSA (p = 0.022). In a multivariate analysis, DM was predicted by OSA in women with an odds ratio (OR) of 11.8, but not by age, body mass index (BMI) at baseline, or weight change at followup. In men, only BMI (OR 1.16) predicted DM. CONCLUSION: The contribution of OSA to DM development seems to be gender dependent and higher in women than in men. PMID- 20572418 TI - Endothelial function in patients with post-CPAP residual sleepiness. AB - STUDY OBJECTIVES: The significance of residual excessive daytime sleepiness (EDS) on cardiovascular markers in patients with adequately treated obstructive sleep apnea (OSA) remains unclear. The objective of this study was to investigate flow mediated dilatation (FMD) and inflammatory markers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in continuous positive airway pressure (CPAP)-compliant patients with residual EDS compared with CPAP compliant patients without residual EDS. METHODS: FMD of the brachial artery was measured by ultrasound in 12 CPAP-compliant patients with OSA who had residual EDS and 12 age-, sex-, and body mass index-matched CPAP-compliant patients with OSA who did not have residual EDS on week 8 after initiation of CPAP. Twelve otherwise-healthy subjects without sleep disordered breathing were used as control subjects. Serum concentrations of CRP, TNF-alpha, and IL-6 were quantified by enzyme-linked immunosorbent assays. RESULTS: Baseline FMD was comparable among CPAP-compliant patients with residual EDS (7.2 +/- 2.3), CPAP compliant patients without residual EDS (8.6 +/- 2.1), and control subjects (7.7 +/- 1.4) (p = 0.37). The concentrations of CRP, TNF-alpha, and IL-6 were also not significantly different between subjects with CPAP-compliant residual EDS and those without residual EDS (p = 0.44, p = 0.37, and p = 0.42; respectively). CONCLUSIONS: Residual EDS in patients with adequately treated OSA may not represent a risk factor for cardiovascular diseases. PMID- 20572419 TI - Increased neck soft tissue mass and worsening of obstructive sleep apnea after growth hormone treatment in men with abdominal obesity. AB - BACKGROUND: Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion. AIM: To study the effect of GH treatment on OSA in abdominally obese men with impaired glucose tolerance. PATIENTS AND METHODS: Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumference. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. RESULTS: GH treatment increased insulin-like growth-factor-1i from (mean [SD]) 168 (72) to 292 (117) microg/L, the apnea-hypopnea index from (n/h) 31 (20) to 43 (25) and oxygen-desaturation index from (n/h) 18 (14) to 29 (21) (p = 0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross sectional area (p = 0.007, 0.01, 0.02) increased, while abdominal visceral adipose tissue (p = 0.007) was reduced. No between-group differences in total sleep time, REM sleep, NREM sleep, and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. CONCLUSIONS: GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be reflected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in abdominally obese men. PMID- 20572420 TI - Prenatal and perinatal complications: is it the link between race and SES and childhood sleep disordered breathing? AB - STUDY OBJECTIVES: Recent evidence has suggested that low socioeconomic status (SES), race, prematurity, and maternal smoking during pregnancy are associated with childhood sleep disordered breathing (SDB). We investigated (1) the association of SDB with a wide range of risk factors, including prenatal and perinatal complications; (2) the association of these complications with SES and race; and (3) the association of SDB with developmental milestones. METHODS: Six hundred thirteen school-aged children (105 clinically referred and 508 community control subjects) underwent overnight polysomnography and had a complete history and physical examination. A comprehensive child development questionnaire was completed by a parent. We compared clinically referred children with SDB to population-based control children without SDB from The Penn State Children's Cohort. RESULTS: Maternal smoking during pregnancy; maternal age and weight gain during pregnancy; prenatal complications, such as maternal high blood pressure and gestational diabetes; perinatal complications related to prematurity; delayed motor milestones; race and SES were significantly associated with the presence of childhood SDB. Most of the risk factors became nonsignificant when analyses controlled for race and SES. Delayed motor milestones remained significantly associated with SDB after controlling for race and SES. CONCLUSION: These data suggest that there is a significant association between children who experience prenatal or perinatal distress and the development of moderate to severe childhood SDB. SES and race may be mediating the impact on SDB through increased prenatal and perinatal risks. The significant delay in motor milestones suggests that prenatal and perinatal distress may result in neurologic insult, which could influence the development of SDB in later childhood. PMID- 20572421 TI - Effect of acute physical exercise on patients with chronic primary insomnia. AB - STUDY OBJECTIVES: The aim was to assess and to compare the acute effects of three different modalities of physical exercise on sleep pattern of patients with chronic primary insomnia. METHODS: Forty-eight insomnia patients, 38 female (mean age 44.4 +/- 8 y) were randomly assigned to 4 groups: control (CTR, n=12), moderate-intensity aerobic exercise (MAE, n=12), high-intensity aerobic exercise (HAE, n=12), and moderate-intensity resistance exercise (MRE, n=12). The patients were assessed on sleep pattern (by polysomnogram and daily sleep log) and anxiety (STAI) before and after the acute exercise. RESULTS: The polysomnogram data showed reduction in the sleep onset latency (SOL) (55%) and in the total wake time (TWT) (30%); increase in total sleep time (TST) (18%), and in the sleep efficiency (SE) (13%) in the MAE group. The daily sleep log data showed increase in the TST (26%) and reduction in the SOL (39%). In addition, reduction (15%) in anxiety was also observed after moderate-intensity aerobic exercise. CONCLUSIONS: Acute moderate-intensity aerobic exercise appears to reduce pre-sleep anxiety and improve sleep in patients with chronic primary insomnia. PMID- 20572422 TI - Decreased nocturnal movements in patients with facioscapulohumeral muscular dystrophy. AB - STUDY OBJECTIVES: Reduced mobility during sleep characterizes a variety of movement disorders and neuromuscular diseases. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy in the general population, and people with FSHD have poor sleep quality. The aims of the present study were to evaluate nocturnal motor activity in patients with FSHD by means of videopolysomnography and to verify whether activity was associated with modifications in sleep structure. METHODS: We enrolled 32 adult patients affected by genetically confirmed FSHD (18 women and 14 men, mean age 45.1 +/- 13.4 years) and 32 matched control subjects, (18 women and 14 men, mean age 45.5 +/- 11.4 years). Major body movements (MBM) were scored in videopolygraphic recordings in accordance with established criteria. An MBM index was calculated (number of MBM per hour of sleep). RESULTS: The FSHD group showed a decrease in the MBM index (FSHD: 1.2 +/- 1.1; control subjects: 2.3 +/- 1.2, analysis of variance F = 13.672; p = 0.008). The sleep pattern of patients with FSHD, as compared with that of controls, was characterized by longer sleep latencies, shorter sleep durations, an increased percentage of wake during sleep, and a decreased percentage of rapid eye movement sleep. In the patient group, the MBM index was inversely correlated with severity of disease (Spearman test: r30 = -0.387; p < 0.05). CONCLUSIONS: The present findings suggest that patients with FSHD have a reduced number of nocturnal movements, which is related to disease severity. Reduced movement in bed may contribute to the sleep modifications observed in these patients. PMID- 20572424 TI - An unusual cause of delirium. AB - Sleep disordered breathing (SDB) including obstructive sleep apnea (OSA), central sleep apnea (CSA), and Cheyne-Stokes breathing is common in patients with congestive heart failure (CHF). In a study of 81 males with an ejection fraction (EF) < 45%, 51% of patients had documented SDB with the majority of cases representing CSA. Studies suggest that SDB is an independent risk factor for increased morbidity and mortality in the setting of CHF. Like OSA, CSA frequently presents with nighttime awakenings, nocturnal hypoxia, and daytime somnolence, but only OSA has been reported to present with delirium. We present a patient with clear manifestations of CSA with frank delirium that improved only after BPAP therapy. PMID- 20572423 TI - Caregiver reports of sleep problems in non-Hispanic white, Hispanic, and African American patients with Alzheimer dementia. AB - STUDY OBJECTIVES: Sleep problems are common in persons with dementing illnesses and among the most stressful patient behaviors for caregivers. Although studies have shown differences in sleep across ethnic groups, little information is available on ethnic differences among persons with dementia. The purpose of this study was to investigate possible ethnic differences in sleep problems among patients with Alzheimer dementia. METHOD: Caregiver reports of 5 sleep- or circadian rhythm-related behavioral problems (behavior disturbance worse in the evening, difficulties falling asleep, frequent awakenings, early awakenings, and excessive daytime sleep) were evaluated in 395 patients who had received a diagnosis of Alzheimer disease after diagnostic evaluation. The average cognitive score of the groups suggested that they could be characterized as having moderately severe impairment. The frequency of sleep problems was then evaluated across subgroups defined by self-reported ethnicity (African American, Hispanic, and non-Hispanic white). As patient and caregiver characteristics may affect caregivers' reports of patients' behaviors, mixed effects regression models were used to adjust for patient and caregiver variables that might affect caregiver reports. RESULTS: Analyses revealed ethnic differences in sleep or circadian rhythm disturbances. African American and Hispanic patients were reported to have more severe sleep disturbances than non-Hispanic whites. After correction for patient and caregiver variables that might have affected caregiver reports, differences between African Americans and others remained. CONCLUSIONS: Sleep problems in patients with dementing illnesses are reported by caregivers with differing frequencies across groups of African Americans, Hispanics, and non Hispanic whites. Clinicians should be aware of these differences in assessing sleep disturbance in patients with dementia as well as the potential effects of patient and caregiver variables on reports of these problems. PMID- 20572426 TI - The early riser. Reassurance. PMID- 20572425 TI - Beyond Ockham's razor: redefining problem-solving in clinical sleep medicine using a "five-finger" approach. AB - The rule of diagnostic parsimony--otherwise known as "Ockham's Razor"--teaches students of medicine to find a single unifying diagnosis to explain a given patient's symptoms. While this approach has merits in some settings, a more comprehensive approach is often needed for patients with chronic, nonspecific presentations for which there is a broad differential diagnosis. The cardinal manifestations of sleep disorders--daytime neurocognitive impairment and subjective sleep disturbances-are examples of such presentations. Successful sleep medicine clinicians therefore approach every patient with the knowledge that multiple diagnoses-rather than simply one-are likely to be found. Teaching an integrated and comprehensive approach to other clinicians in an organized and reproducible fashion is challenging, and the evaluation of effectiveness of such teaching is even more so. As a practical aid for teaching the approach to--and evaluation of--a comprehensive sleep medicine encounter, five functional domains of sleep medicine clinical problem-solving are presented as potential sources for sleep/wake disruption: (1) circadian misalignment, (2) pharmacologic factors, (3) medical factors, (4) psychiatric/psychosocial factors, and (5) primary sleep medicine diagnoses. These domains are presented and explained in an easy-to remember "five finger" format. The five finger format can be used in real time to evaluate the completeness of a clinical encounter, or can be used in the design of standardized patients to identify areas of strength and potential weakness. A score sheet based upon this approach is offered as an alternative to commonly used Likert scales as a potentially more objective and practical measure of clinical problem-solving competence, making it useful for training programs striving to achieve or maintain fellowship accreditation. PMID- 20572427 TI - Research mentorship from the mentor's perspective. PMID- 20572428 TI - Oncology patients' and nurses' perceptions of caring. AB - The concept of caring is central to the practice of nursing. Recent focus on patient-centred care highlights the importance of viewing caring from the patient's perspective. A comparative descriptive cross-sectional study was conducted to determine if there was a difference in oncology patients' and nurses' perceptions of caring. The Caring Behaviors Inventory-Elders (CBI-E) directly derived from Watson's Theory of Human Caring was administered to patients and nurses from in-patient medical-surgical units. This paper reports on a subset of 19 patients and 15 nurses from the oncology unit. There were significant differences between patients' and nurses' perceptions on overall caring and on several individual behaviours. In order to provide true patient centred care, innovative approaches to addressing these differences are needed. PMID- 20572429 TI - Identifying supportive care needs of women with ovarian cancer. AB - Women diagnosed with ovarian cancer may experience many shortterm and long-term effects from cancer and its treatment. Cancer has more than a physical impact, yet there is a lack of information about the types of needs these women have and whether they want help in meeting their needs. The main purpose of this cross sectional, descriptive study was to identify the supportive care needs (physical, emotional, social, informational, spiritual, psychological and practical) of women with ovarian cancer who attended a comprehensive, outpatient cancer centre. A further purpose was to determine if women wanted assistance in meeting those needs. A total of 50 women diagnosed with ovarian cancer participated in this study by completing a self-report questionnaire (The Supportive Care Needs Survey). The data indicated that a range of supportive care needs remained unmet for this patient group. Eight of the top 10 most frequently reported needs were psychosocial, such as fears about the cancer returning or spreading. The women also expressed a range of difficulty in managing their needs. However, despite this reality, significant numbers of women indicated they did not wish to have assistance from the clinic staff with some needs. Suggestions for practice and future research are offered to assist oncology nurses in providing care to these women. PMID- 20572430 TI - Utility of routine nurse assessment of the risk of chemotherapy-induced febrile neutropenia. AB - Evidence-based guidelines recommend that patients at high risk (> or = 20%) for febrile neutropenia (FN) should receive prophylactic colony-stimulating factors (Aapro et al., 2006; Kouroukis et al., 2008; National Comprehensive Cancer Network [NCCN], 2008; Smith et al., 2006). We studied the utility of having nurses routinely assess FN risk in new patients before the initiation of chemotherapy. Fifteen nurses used a standardized tool to evaluate FN risk in 150 patients. In 94% of patients studied, nurses detected risk factors that prompted interventions to reduce the incidence of FN. On final evaluation, 67% of nurses said the use of a standardized tool helped them to identify patients at risk for FN, and 73% planned to assess FN risk routinely. Thus, it is feasible and valuable for nurses to assess FN risk using a standardized checklist prior to the initiation of chemotherapy. PMID- 20572431 TI - The clinical nurse specialist as nurse navigator: ordinary role presents extraordinary experience. PMID- 20572432 TI - Evaluating the benefits of exercise for women receiving adjuvant therapy for breast cancer: research challenges. PMID- 20572433 TI - Comprehensive psychosocial care: an innovative approach: new program development. PMID- 20572434 TI - Did you know? A question and answer dialogue for the orofacial myologist. AB - This article addresses selected concepts and procedures related to orofacial myology in a question and answer format. Topics include tongue-tip placement for swallowing; a masseter-contraction swallow; temporary anchorage devices utilized in orthodontic treatment; relapse following orthodontic treatment; some advantages and disadvantages of fixed and removable orthodontic appliances; the extraction of teeth in orthodontic treatment; posterior and anterior crossbite considerations; and the importance of recasting the emphasis and focus of myofunctional therapy to orofacial rest posture therapy. In addition, this article promotes projects that orofacial myologists and orthodontists can mutually undertake to assist in advancing the data base regarding orofacial myofunctional disorders, thereby serving to enhance the reputation and value of orofacial myofunctional therapy within the dental profession. PMID- 20572435 TI - Clinical and electromyographic study of lateral preference in mastication in patients with longstanding peripheral facial paralysis. AB - Peripheral facial paralysis (PFP) usually affects the facial nerve in part or in whole on one side of the face. Most patients with acute PFP find it difficult to chew on the paralyzed side, especially due to compromised buccinator function. In addition, the sagging of the ipsilateral lip commissure tends to compromise lip competence. The purpose of this study was to evaluate the impact of long-standing PFP upon mastication, relating to clinical mastication sidedness as determined by clinical and electromyographic activity of the masseters. The study included 27 male and female subjects aged 16-69 years with permanent natural dentition and long-standing PFP. Patients answered questions on their mastication habits before and after onset of PFP and were submitted to clinical myofunctional examination and electromyographical tests of the masseters during clenching and habitual mastication. According to the anamnesis, 77.8 % claimed to prefer chewing on the unaffected side. Clinically, 70% presented a lateral preference in mastication. In the clinical evaluation the buccinators and orbicularis oris differed significantly (p = 0.025) between the healthy and the paralyzed side. Only 22.2% of the patients showed increased thickness of the contralateral masseters. No statistically significant electromyographic difference was observed between the masseters on the affected and unaffected side. Conclusions In general indicated that subjects with flaccid-stage PFP for 6 months or longer preferred to masticate on the unaffected side. No significant clinical or electromyographic differences were found in masseter activity between the affected and unaffected side in this patient sample. PMID- 20572436 TI - Lip-closing function of elderly people during ingestion: comparison with young adults. AB - In this study the relationship between the functional vertical labial pressure and aging during ingestion in the elderly is examined. The subjects were 84 community-dwelling elderly (mean: 79.4 years old), 109 elderly needing long term care (mean: 81.3 years old), and 59 healthy young adults (mean: 32.0 years old) as control. Labial pressure was measured with a pressure sensor embedded in acrylic plate. There was no correlation between age and labial pressure or the coefficient of variation of labial pressure during ingestion. In people with a history of "choking on food", labial pressure was, however, significantly lower (p < 0.01) than people without a history of "choking on food", while the coefficient of variation of labial pressure was significantly higher (p < 0.05). Poor labial pressure and movement were noted in subjects who experienced "choking on food", suggesting that lip-closing function also plays an important role in the pharyngeal stage of feeding/swallowing. On the other hand, the coefficient of variation of labial pressure during ingestion was not changed in the elderly group in comparison to the control group. These results showed that skilled movement of lip-closing might be compensated by labial pressure. Labial pressure and skilled movement were, however, decreased in the elderly needing care because of "choking on food". PMID- 20572437 TI - Quantitative evaluation of the orofacial morphology: anthropometric measurements in healthy and mouth-breathing children. AB - The anthropometric orofacial measurements of mouth-breathing children were compared to those of children with no history of speech-language disorders, according to age. METHODS: 100 children participated, both males and females, with ages ranging from 7 to 11 years and 11 months, leukoderm, in mixed dentition period, with a mouth-breathing diagnosis. The control group was comprised of 254 children, of both sexes, with ages ranging from 7 to 11 years and 11 months, leukoderm, in mixed dentition period, with no history of speech-language disorders. The control group did not demonstrate any mouth-breathing. The children were submitted to anthropometric assessment and the orofacial measurements obtained were upper lip, lower lip, philtrum, upper face, middle face, lower face, and sides of the face. The instrument used was the electronic digital sliding caliper Starrett Series 727. There was statistically significant difference between the majority of the orofacial measurements of mouth-breathing children and the measurements of children with no history of speech-language disorders. Some orofacial measurements were different in the studied populations. The possibility of comparing orofacial measurements of children with and without mouth-breathing behavior allows the clinician to determine normal and altered structures of the orofacial morphology. The main advantages of the anthropometry are its noninvasive nature, its technological simplicity, low cost and objective analysis. The anthropometric procedures also have clinical applications in myofunctional assessment and therapy. PMID- 20572438 TI - Concomitant trichotillomania cessation and thumb-sucking elimination: of course, they're related...aren't they? AB - This article presents an overview of the current research literature that reveals some controversy, discussion of the need for more research, and report of some definitive success. In addition, four case studies of hair pulling and thumb sucking are highlighted. PMID- 20572439 TI - Position statement of the International Association of Orofacial Myology regarding: appliance use for oral habit patterns. PMID- 20572440 TI - Position statement of the International Association of Orofacial Myology regarding: orofacial myologist providing clinical services via telepractice: postion statement. PMID- 20572441 TI - [Kangaroo Mother Care Department in Kapstadt receives tombola proceeds of the Breast Feeding and Lactation Congress in Hamburg]. PMID- 20572442 TI - [Overweight status of Turkish children. Research of the cause]. PMID- 20572443 TI - [BeKD organizes new "pediatric intensive care nursing" section. A bridge between clinical and home nursing]. PMID- 20572444 TI - [Improved nursing care after hypospadias correction by transurethral urinary catheterization with the "dripping stent"]. PMID- 20572445 TI - [Self healing power and placebo effect]. PMID- 20572446 TI - [Secure bonding to the caregiver--prerequisite for successful development]. PMID- 20572447 TI - [Congenital deafness--causes]. PMID- 20572448 TI - [Have you heard? New studies and publications on the topic of hearing]. PMID- 20572449 TI - ["The future begins yesterday". Suicide prevention in children and adolescents]. PMID- 20572450 TI - [Haiti after the earthquake. A pediatric clinic in Port-au-Prince as partner and sponsor clinic]. PMID- 20572451 TI - [Gastrostomy tubes--nursing and legal questions]. PMID- 20572452 TI - [Patient safety and reality in medical care: every 3rd German fears coming to harm in the hospital or physician's office]. PMID- 20572453 TI - [Coffee does not cause dehydration!]. PMID- 20572454 TI - The role of dispersed nocardioform filaments in activated sludge foaming. AB - Activated sludge foaming caused by filamentous microorganisms is a major wastewater treatment plant operating problem. This paper presents the results of an investigation of the role of dispersed nocardioforms in activated sludge foaming. Dispersed nocardioforms had a greater propensity for foaming than floc bound nocardioforms. The mode of effluent withdrawal from an aeration basin plays a major role in determining the relative proportion of dispersed and floc-bound nocardioforms in the activated sludge. Reactors with "trapping" features (sub surface mixed liquor withdrawal) had significantly higher dispersed nocardioform populations than reactors with "non-trapping" features (surface mixed liquor withdrawal). High dispersed nocardioform filament concentrations were correlated with a high propensity for foaming. Cationic polymer and polyaluminum chloride reduced foaming by flocculating dispersed nocardioforms, thereby converting them to floc-bound nocardioforms. Low non-ionic surfactant concentrations changed the relative proportions of dispersed and floc-bound nocardioforms by deflocculating floc-bound filaments and converting them to the dispersed growth form. This could act as a trigger for initiating the rapid-onset nocardioform foaming events observed at activated sludge plants. PMID- 20572455 TI - Selecting the most relevant variables for anaerobic digestion imbalances: two case studies. AB - In this study, a wrapper approach was applied to objectively select the most important variables related to two different anaerobic digestion imbalances, acidogenic states and foaming. This feature selection method, implemented in artificial neural networks (ANN), was performed using input and output data from a fully instrumented pilot plant (1 m3 upflow fixed bed digester). Results for acidogenic states showed that pH, volatile fatty acids, and inflow rate were the most relevant variables. Results for foaming showed that inflow rate and total organic carbon were among the relevant variables, both of which were related to the feed loading of the digester. Because there is not a complete agreement on the causes of foaming, these results highlight the role of digester feeding patterns in the development of foaming. PMID- 20572456 TI - Bacterial attachment and detachment in aluminum-coated quartz sand in response to ionic strength change. AB - Column experiments were performed to investigate the effect of ionic strength on the attachment and detachment of Staphylococcus aureus ATCC 10537 and Bacillus subtilis ATCC 6633 in aluminum-coated quartz sand. Results showed that the average mass recovery decreased from 80.7 to 45.3% in quartz sand and remained constant in aluminum-coated sand with increasing ionic concentrations of sodium chloride solution from 1 to 100 mmol/L. As the ionic concentrations of leaching solution changed from 100 to 0.1 mmol/L, average mass recovery of 39.1% was obtained from quartz sand (bacterial release), but no detachment was observed from aluminum-coated sand. This lack of detachment can be attributed to inner sphere complexes between bacteria and aluminum-coated sand, which are minimally affected by ionic strength. This research indicates that aluminum-coated sand has advantages over quartz sand in bacteria removal in water filtration systems. PMID- 20572457 TI - Colloid-facilitated metal transport in peat filters. AB - The effect of colloids on metal retention in peat columns was studied, with the focus on colloids from two sources-organic matter leached from peat, and introduced organic and hydrous ferric oxide (HFO) colloids. A significant fraction of metals was found to be associated with peat-produced organic colloids; however the concentrations of organic colloids leached are low (trace concentrations) and temporal and have a limited effect on the efficiency of peat filters. In contrast, the presence of organic and HFO colloids in the input water causes a significant decrease in the performance of peat filters. Organic colloids were identified as the main vector of cadmium, copper, nickel, and zinc, while lead is transported by both organic and HFO colloids. The colloidal distribution of metals obtained in this study has important implications for the mobility of trace metals in porous media. The occurrence of colloids in the input waters and their characteristics must be considered when designing water treatment facilities. PMID- 20572458 TI - Cold climate performance analysis of on-site domestic wastewater treatment systems. AB - Household on-site septic systems with secondary wastewater treatment in Anchorage, Alaska, were sampled and analyzed for performance parameters during the winter to spring months. System types included intermittent dosing sand filters (ISF), three types of recirculating trickling filters (RTF), and suspended-growth aeration tanks. Total nitrogen from the trickling filter and aeration tank effluent was fairly uniform, at approximately 30 mg/L. Total suspended solids (TSS) means were mostly less than 15 mg/L. The 5-day biochemical oxygen demand (BODs) showed considerable variability, with means ranging from 9.2 mg/ L for ISFs up to 39.5 mg/L for one type of RTF, even though this type has shown excellent results in several test programs. The data suggested that effluent temperature within the sample range had almost no effect on effluent concentrations of BOD5 or TSS and only a small effect on the removal of total nitrogen. Non-climatic factors were probably of equal importance to treatment results. PMID- 20572459 TI - The influence of sludge interchange times on the oxic-settling-anoxic process. AB - The oxic-settling-anoxic (OSA) system operated as a sequencing batch reactor was studied. Sludge was interchanged between the aerobic and anaerobic reactors, and the number of daily interchange times was changed from 1 to 4 during the experiments. When the sludge was interchanged 1 time/d, the reduction of excess sludge mass was only 52.8%. When the sludge was interchanged 4 times/d, the reduction of excess sludge mass was 77.4%; reductions in the total chemical oxygen demand, total solids, and total volatile solids of both the anaerobic sludge and the aerobic settled sludge were the greatest; and more soluble iron was released from the anaerobic sludge. The water quality of the final effluent in the two systems was close. The investigation showed that interchange times are important in improving sludge reduction efficiency, and the parameter should be regarded as an important operating factor in the OSA process. PMID- 20572460 TI - Bioaugmentation to improve nitrification in activated sludge treatment. AB - Bioaugmentation is a proposed technique to improve nutrient removal in municipal wastewater treatment. Compared with commonly used nitrification/denitrification (NDN) processes, bioaugmentation may be able to reduce tankage or land requirements. Many approaches for bioaugmentation have been developed, but few studies have compared the benefits among different approaches. This paper quantifies the effectiveness of bioaugmentation processes and investigates three major "onsite" bioaugmentation alternatives: 1) the parallel-plants approach, which uses acclimated biomass grown in a nitrifying "long-SRT" (sludge retention time) plant to augment a low-SRT treatment plant; 2) the enricher-reactor approach, which uses an offline reactor to produce the augmentation cultures; and 3) the enricher-reactor/return activated sludge (ER-RAS) approach, which grows enrichment culture in a reaeration reactor that receives a portion of the recycle activated sludge. Kinetic models were developed to simulate each approach, and the benefits of various approaches are presented on the same basis with controllable parameters, such as bioaugmentation levels, aeration tank volume, and temperatures. Examples were given to illustrate the potential benefits of bioaugmentation by upgrading a "carbon-only" wastewater treatment plant to nitrification. Simulation results suggested that all bioaugmentation approaches can decrease the minimum SRT for nitrification. The parallel-plants approach creates the highest concentration of biomass but may fail at too low temperature. The ER-RAS approach likely would be more useful at lower temperature and required less reactor volume; enricher-reactor approach would likely be more advantageous in the presence of inhibitory compound(s). PMID- 20572461 TI - Interaction between denitrification and phosphorus removal in a sequencing batch reactor phosphorus removal system. AB - Batch experiments were performed to investigate simultaneous denitrification and phosphorus removal by denitrifying phosphorus accumulating organisms (DNPAO). The results showed that while using the same amount of carbon source, DNPAOs are able to uptake phosphorus by using nitrate as an electron acceptor. It was observed that higher nitrate concentration required a longer anoxic period for denitrifying phosphate uptake. In addition, the effect of the presence of nitrate in substrate was studied. Phosphorus release occurred as long as substrate was present in the anaerobic phase regardless of nitrate concentrations. It also was noticed that nitrate hindered the release of phosphorus in the anaerobic stage because of denitrifiers competing with phosphorus accumulating organisms for their carbon source. The DNPAOs, however, remained competitive in a system with nitrate in the anaerobic phase. PMID- 20572462 TI - Investigating the fundamental basis for selectors to improve activated sludge settling. AB - Aerobic, anoxic, and anaerobic selectors have become popular for controlling filamentous bulking in activated sludge systems; however, selectors are not always successful. Regression analyses of data collected from 48 full-scale wastewater treatment plants, with operating selectors, provided a method for ranking the importance of selector operating and design parameters (with respect to their influence on activated sludge settleability) and suggests optimum numerical ranges for these parameters for best selector performance. Selectors do not appear to control filamentous bulking in long mean cell residence time (MCRT) plants. Further, the elimination of all selector zones may help to control bulking in these plants. However, other design/operating parameters were shown to influence activated sludge settleability in long-MCRT plants. Aerobic selectors in short-MCRT plants can control filamentous bulking, if they are small enough to produce a biochemical oxygen demand (BOD) concentration gradient. Anoxic and anaerobic selectors can control filamentous bulking in short-MCRT plants, if the selector volume is large enough and/or the selector mixed-liquor suspended solids concentration is high enough. These unaerated selector systems do not appear to benefit from a BOD concentration gradient as the aerobic selectors in short-MCRT plants do. Although anaerobic/anoxic selector compartmentalization in these plants appears to improve settleability, this presumably is because of reduced selector short-circuiting. PMID- 20572463 TI - Factorial analysis of trihalomethanes formation in drinking water. AB - Disinfection of drinking water reduces pathogenic infection, but may pose risks to human health through the formation of disinfection byproducts. The effects of different factors on the formation of trihalomethanes were investigated using a statistically designed experimental program, and a predictive model for trihalomethanes formation was developed. Synthetic water samples with different factor levels were produced, and trihalomethanes concentrations were measured. A replicated fractional factorial design with center points was performed, and significant factors were identified through statistical analysis. A second-order trihalomethanes formation model was developed from 92 experiments, and the statistical adequacy was assessed through appropriate diagnostics. This model was validated using additional data from the Drinking Water Surveillance Program database and was applied to the Smiths Falls water supply system in Ontario, Canada. The model predictions were correlated strongly to the measured trihalomethanes, with correlations of 0.95 and 0.91, respectively. The resulting model can assist in analyzing risk-cost tradeoffs in the design and operation of water supply systems. PMID- 20572464 TI - Kinetic and thermodynamic studies on the adsorption of anionic surfactant on quaternary ammonium cationic cellulose. AB - Removal of anionic surfactants from aqueous solutions by adsorption onto quaternary ammonium cationic cellulose (QACC) was investigated. The effects of solution acidity, initial concentration, adsorption time, and temperature on the adsorption of sodium dodecyl-benzene sulfonate (SDBS), sodium lauryl sulfate (SLS), and sodium dodecyl sulfonate (SDS) were studied. The kinetic experimental data fit well with the pseudo-second-order model; the rate constant of the adsorption increased with temperature. The values of apparent activation energy for the adsorption were calculated as ranging from 10.2 to 17.4 kJ/ mol. The adsorption isotherm can be described by the Langmuir isotherm. The values of thermodynamic parameters (deltaH0, deltaS0, and deltaG0) for the adsorption indicated that this process was spontaneous and endothermic. At 318 K, the saturated adsorption capacities of QACC for SDBS, SLS, and SDS were 1.75, 1.53, and 1.39 mmol/g, respectively. The adsorption process was mainly chemisorption and partially physisorption. The results show that QACC is effective for the removal of anionic surfactants. PMID- 20572465 TI - Ventricular fibrillation in an individual using the dietary supplement Lipodrene. PMID- 20572466 TI - Millennial transformation for primary care. AB - We do not need a crystal ball to see the future. Our web-based future has already arrived in all other aspects of our lives--even our mobile phones. The tools for progress--Personal Health Records, Social Networks, and Online medical information--are widely available. The demand is at hand--Millennials are flexing consumer muscles as they enter the healthcare market. Real "Health Care Reform" requires fundamental changes in practice--which in turn requires effective use of information technologies and adaption to changing consumer expectations. The VHA and the MHS are uniquely capable of leveraging political, academic and technological forces to help move American health care through this millennial transformation. Federal health systems are positioned to demonstrate the value of innovation as America seeks healthcare reform. PMID- 20572467 TI - Military organizations and programs contributing to resilience building. PMID- 20572468 TI - A sense of purpose. PMID- 20572469 TI - 2010 Conference on Infectious Disease Modeling sponsored by the U.S. Department of Defense. PMID- 20572470 TI - Substance use and mental health trends among U.S. military active duty personnel: key findings from the 2008 DoD Health Behavior Survey. AB - OBJECTIVE: Examine substance use and mental health issues among U.S. military personnel. METHODS: Data were from the 2008 (and before) population-based Department of Defense Health Related Behavior Surveys. The sample size for the 2008 survey was 28,546 (70.6% response rate). RESULTS: Analyses examined substance use, stress, depression, post-traumatic stress disorder (PTSD), suicidal ideation and attempts, deployment, and job satisfaction. Trends show reductions in tobacco use and illicit drug use, but increases in prescription drug misuse, heavy alcohol use, stress, PTSD, and suicidal attempts. Deployment exacerbated some of these behavior changes. Despite the demanding lifestyle, job satisfaction was high. CONCLUSIONS: The military has shown progress in decreasing cigarette smoking and illicit drug use. Additional emphasis should be placed on understanding increases in prescription drug misuse, heavy alcohol use, PTSD, and suicide attempts, and on planning additional effective interventions and prevention programs. Challenges remain in understanding and addressing military mental health needs. PMID- 20572471 TI - Stress and alcohol use among soldiers assessed at mobilization and demobilization. AB - Excessive alcohol use may have negative consequences, including less force readiness among military personnel. The identification of variables associated with alcohol use may inform early intervention efforts to decrease negative consequences. This longitudinal prospective study examined the associations of demographic and stress variables with alcohol use among 876 soldiers that were mobilized and demobilized through an Army installation during a 9-month period in 2003. Participants reported a moderate level of general stress at mobilization and demobilization, and a minority reported significant combat stress. Alcohol use in the 2 weeks before the demobilization evaluation was associated with younger age, nonactive duty status before mobilization, and more general stress. Male gender was associated with more drinks per drinking day. The results suggest that younger, nonactive duty male personnel experiencing stress may be a group at risk for increased drinking after deployment and for whom intervention may be helpful. PMID- 20572472 TI - Characterizing aggression and its association to anger and hostility among male veterans with post-traumatic stress disorder. AB - OBJECTIVES: The basis for the associations among anger, hostility, aggressive behavior, and post-traumatic stress disorder (PTSD) remains unclear. We suggest classifying aggressive behavior may elucidate the associations among these factors. On the basis of diagnostic and neurobiological similarities between impulsive aggression (IA) and PTSD, we proposed that IA was the predominant form of aggression in PTSD and that anger and hostility would not significantly predict PTSD when IA was also included as a predictor. METHODS: We used cross sectional self-report data obtained from two samples of male veterans (N = 136). RESULTS: Over 70% of veterans with PTSD reported IA compared to 29% of those without PTSD. IA, not anger, hostility, or premeditated aggression significantly predicted a diagnosis of PTSD. CONCLUSIONS: Associations between anger and PTSD may be unique to individuals with IA, and considering impulsive and premeditated aggressors separately may account for the heterogeneity found within samples of aggressive veterans with PTSD. PMID- 20572473 TI - Driving rehabilitation for military personnel recovering from traumatic brain injury using virtual reality driving simulation: a feasibility study. AB - OBJECTIVE: To investigate the feasibility of virtual reality driving simulation rehabilitation training (VRDSRT) with military personnel recovering from traumatic brain injury (TBI). METHODS: Eleven men with TBI were randomly assigned as controls (n = 5) receiving residential rehabilitation only or the VRDSRT group (n = 6) receiving residential rehabilitation and VRDSRT. All subjects underwent pre- and post-assessments including simulator driving, and completing road rage and risky driving questionnaires. Between assessments, VRDSRT subjects received 4 6, 60- to 90-min rehabilitation training sessions involving practicing progressively more complex driving skills (lane position, speed control, etc.) through progressively more demanding traffic. RESULTS: VRDSRT was well received, considered realistic and effective, with no reported simulation sickness. Driving performance improved significantly in the VRDSRT group only (p < 0.01). They also demonstrated a reduction in road rage (p = 0.01) and risky driving (p = 0.04) at post-assessment. CONCLUSION: VRDSRT showed promising results with respect to retraining driving performance and behavior among military personnel recovering from TBI. PMID- 20572475 TI - The role of emotional numbing in sexual functioning among veterans of the Iraq and Afghanistan wars. AB - Post-traumatic stress disorder (PTSD) negatively impacts sexuality, yet few studies have evaluated which component of PTSD contributes to this known association. The present study examined which of four PTSD clusters (numbing, avoidance, intrusiveness, and hyperarousal) was most closely linked to sexual problems in a sample of 197 veterans from the Iraq or Afghanistan wars. Newly registered veterans completed a packet of questionnaires including standardized measures of PTSD and questions regarding sexual functioning. A stepwise logistic regression was performed to examine the relationship between symptom cluster and sexual functioning. As predicted, only the numbing cluster was retained in the regression model. The numbing cluster appears to be intimately tied to sexual functioning, assessment of which should be part of a comprehensive evaluation during the postdeployment readjustment phase. Those exhibiting numbing symptoms should be thoroughly assessed for sexual functioning problems and referred for treatment as necessary. PMID- 20572474 TI - Effect of a 13-month deployment to Iraq on physical fitness and body composition. AB - This investigation evaluated the effects of a 13-month deployment to Iraq on body composition and selected fitness measures. Seventy-three combat arms soldiers were measured pre- and postdeployment. Body composition was assessed by dual X ray absorptiometry (DXA). Strength was measured by single repetition maximum (1 RM) lifts on bench press and squat. Power was assessed by a bench throw and squat jump. Aerobic endurance was evaluated with a timed 2-mile run. Exercise and injury history were assessed by questionnaire. Upper and lower body strength improved by 7% and 8%, respectively (p < 0.001). Upper body power increased 9% (p < 0.001) and lean mass increased 3% (p < 0.05). In contrast, aerobic performance declined 13% (p < 0.001) and fat mass increased 9% (p < 0.05). Fewer soldiers participated in aerobic exercise or sports during deployment (p < 0.001). Unit commanders should be aware of potential fitness and body composition changes during deployment and develop physical training programs to enhance fitness following deployment. PMID- 20572476 TI - Evaluation of a sexual assault education/prevention program for male U.S. Navy personnel. AB - A randomized clinical trial was conducted to evaluate the effectiveness of the Navy Sexual Assault Intervention Training (SAIT) program for men. A four-group Solomon design was used to control for possible pretest sensitization effects. Male Navy personnel (N = 1,505) were assessed for rape knowledge, rape myth acceptance (two scales), and rape empathy after participating in the SAIT program or viewing an educational video about HIV/AIDS (comparison condition). The SAIT program was found to be effective in increasing rape knowledge, reducing rape myth acceptance, and increasing empathy for rape victims. As expected, men who had exhibited previous coercive sexual behavior, compared with those who had not, reported lower levels of knowledge, higher levels of rape myth acceptance, and less rape empathy. However, the SAIT program was generally effective in changing men's knowledge, beliefs, and feelings on the key measures, regardless of participants' histories of coercive sexual behavior. PMID- 20572477 TI - Nursing burnout: cross-sectional study at a large Army hospital. AB - The purpose of this study was to examine the levels of burnout among U.S. Army and civilian nursing personnel assigned to a large military treatment facility. Using a cross-sectional design, a convenience sample of eligible participants (n = 364) completed the Maslach Burnout Inventory. T-test and ordinal logistic regression were used to analyze data. Findings suggest that both groups were experiencing a moderate level of burnout. However, civilian nursing personnel demonstrated statistical lower levels of emotional exhaustion and depersonalization. Findings suggest that nursing personnel who worked the day shift, no more than 8 hours a day and had fewer patient care contacts with military personnel injured in Iraq or Afghanistan reported lower levels of emotional exhaustion and depersonalization. This study provides ideas for policy changes at medical treatment facilities that are experiencing similar challenges. PMID- 20572478 TI - A physical therapist experience, observation, and practice with an infantry brigade combat team in support of Operation Iraqi Freedom. AB - BACKGROUND: In 2005 the first physical therapists were employed in direct support of infantry brigade combat teams (BCTs) during a combat deployment. The initiative sought to bring soldiers direct access to specialized musculoskeletal care at the places they work and live. The goal was to prevent deferment of care for injuries that may become chronic and to decrease medical evacuations for orthopedic nonbattle injuries by locally providing acute and definitive management. PURPOSE: To describe the experience of a newly authorized physical therapy role in direct support of an infantry BCT in Iraq during Operation Iraqi Freedom (OIF). The practice patterns, observation, and utilization of the physical therapy team are reported, to include demographics, injury prevalence, and outcomes. DISCUSSION: Physical therapists should be part of the risk management team and advise unit commanders on injury-prevention strategies in a combat setting. PMID- 20572479 TI - Using qualitative data from a program director's evaluation form as an outcome measurement for medical school. AB - BACKGROUND: Medical education programs need outcome measurements to promote curriculum improvement and to help meet accreditation standards. PURPOSE: Determine the added value of qualitative comments written by program directors (PDs) in response to a survey concerning first postgraduate year (PGY-1) graduates. We hypothesized that these comments would serve as an additional outcome measurement for our graduates, adding information not readily captured in numeric data. METHODS: PD evaluation form surveys from 1993-2002. All qualitative comments offered in response to free text questions were coded and compared with numeric ratings. RESULTS: A total of 1,247 surveys were included (80% response rate). Comments about specific graduates were coded as positive, negative, or neutral and were categorized into themes. Inter-rater reliability was high (kappa= 0.82). Compared with 4% of graduates who received one or more numeric ratings of less than satisfactory, 7% had one or more qualitative phrases classified as negative. CONCLUSIONS: Qualitative comments can serve as a useful outcome measurement. PMID- 20572480 TI - Are 25-hydroxyvitamin D levels adequately monitored following evidence of vitamin D insufficiency in veterans? AB - Vitamin D insufficiency remains a costly pandemic in veterans. Treatment requires achievement of desired 25-hydroxyvitamin D [25(OH)D] concentrations. The frequency with which 25(OH)D should be measured following treatment remains speculative. A retrospective analysis of veterans with vitamin D insufficiency was conducted. The group was stratified on the basis of initial 25(OH)D and assessed for frequency of follow-up 25(OH)D concentrations. Over 3 years, 278 patients with insufficient 25(OH)D concentrations were identified. Of these, 87 (31%) patients had subsequent levels assessed in the year following initial documentation of vitamin D insufficiency. The likelihood of follow-up testing was unrelated to the initial vitamin D level. In the patients with follow-up 25(OH)D levels, 90% eventually achieved a serum level of 30 ng/mL or greater. Veterans with vitamin D insufficiency have inadequate serial monitoring of 25(OH)D concentrations. PMID- 20572481 TI - Fluoroquinolone-associated bilateral patellar tendon rupture: a case report and review of the literature. AB - Single series case reports have described bilateral traumatic patellar tendon ruptures, and less frequently, with little or no trauma. Patellar tendon rupture most often occurs in patients younger than 40 years old and is commonly precipitated by a sudden, significant eccentric contraction. Patellar tendon ruptures are uncommon in those older than 40 years of age, but when they occur, may indicate an underlying systemic disorder. Corticosteroid injections, rheumatic disease, metabolic disorders, and fluoroquinolone use have all been associated with increased risk of tendon rupture. While the Achilles tendon is the most commonly affected by fluoroquinolone use, cases involving the rotator cuff, biceps, wrist extensors, and quadriceps tendon among others, have been described. A case is presented of a 43-year-old man without pre-existing medical comorbidities who sustained atraumatic bilateral patellar tendon ruptures following a treatment course of fluoroquinolone medication. PMID- 20572482 TI - Radiology corner. Complete rupture of the distal biceps tendon. PMID- 20572483 TI - Healthcare reform has passed--now what? PMID- 20572484 TI - Soothe billing nightmares with separate codes for visits. PMID- 20572485 TI - How do you handle the destruction of patient records? PMID- 20572486 TI - How healthcare reform provisions affect your practice. PMID- 20572487 TI - Getting paid for what you do. PMID- 20572489 TI - Maintaining EMR security and confidentiality. PMID- 20572488 TI - Healthcare reform: the devil is in the details. PMID- 20572490 TI - Opportunity in crisis. How your practice can make the most of a reformed healthcare system. PMID- 20572491 TI - Will your physician-hospital alignment strategies succeed? Tips on predicting a workable union. PMID- 20572492 TI - Are the phones ringing off the hook? PMID- 20572493 TI - What Massachusetts learned from healthcare reform. PMID- 20572494 TI - Using VoIP in a medium-size practice call center. AB - The telephone is your practice's lifeline. Learn how one group applied new phone technology to improve service to patients, foster operational efficiencies and capture more revenue. PMID- 20572495 TI - Preventing data disasters: helpful tips on data backup and storage options. AB - Ask vendors about data backup and recovery options when evaluating electronic health record systems. Weigh different solutions for recovery point objectives and recovery time objectives against your practice owners' risk tolerance as well as the budget. PMID- 20572496 TI - [Vitrectomy with intravitreal antibiotic administration in exogenous endophthalmitis treatment in eyes with vision better than light perception]. AB - PURPOSE: To evaluate vitrectomy with intravitreal antibiotic administration in exogenous endophthalmitis treatment in eyes with vision better than light perception. MATERIAL AND METHODS: Retrospective review of 9 patients with exogenous endophthalmitis and VA better than light perception. All patients were treated with vitrectomy and intravitreal antibiotic administration. Outcome measures included: preoperative visual acuity and postoperative visual acuity at 6 months, time from the initial ocular surgery and the presentation of endophthalmitis symptoms. RESULTS: Visual acuity at 6 months improved in 88% (8/9), of patients and decreased in 12% (1/9). The mean change in visual acuity was a gain 1.01 +/- 0.80 logMAR that corresponds to improvements of 10 lines on ETDRS chart. The differences in mean preoperative and postoperative visual acuity were statistically significant (p = 0.009, Wilcoxon signed rank test). No statistically significant differences were detected in mean visual acuity improvement between acute and chronic form of endophthalmitis (p = 0.88, Wilcoxon rank sum test). CONCLUSIONS: There is more evidence to consider vitrectomy with intravitreal antibiotic administration in eyes with visual acuity better than light perception i.e. in cases that Endophthalmitis Vitrectomy Study (EVS) recommends for intravitreal antibiotic administration alone. PMID- 20572497 TI - [Combined surgical and pharmacological treatment of diabetic maculopathy]. AB - There are at least three avenues of investigation that support the theoretical value of vitrectomy for the treatment of DME, based on (1) vitrectomy with ILM peeling for the relief of traction on the macula, (2) vitrectomy to improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME, and (3) ILM peeling to remove a part of the Muller cell endfeet and the horizontal gliosis. Visual improvement could be due to the induction of a higher overexpression of GFAP at the Muller cells level. It is likely that the proliferation of GFAP-stained gliofibrils, observed in these cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. In addition, the search for a specific pharmacological treatment is ongoing on the basis of new findings regarding the involvement of cytokines and growth factors in the formation of macular edema. Vascular endothelial growth factor (VEGF), inhibitors are currently being investigated in clinical studies. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Muller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution. PMID- 20572498 TI - [Changes of the retinal thickness in the macula region in primary open-angle glaucoma patients measured with RTA analyzer]. AB - PURPOSE: Aim of the study is to determinate retinal thickness in macula region in primary open-angle glaucoma patients and in patients suspected of primary open angle glaucoma--by using retinal thickness analyzer RTA, as well as evaluation of the applicability of the method in the early diagnosis of primary open-angle glaucoma. MATERIAL AND METHODS: Fifty primary open-angle glaucoma patient (95 eyes, average age 43.7 +/- 9.0 years), and 67 patients suspected of primary open angle glaucoma (128 eyes, average age 43.2 +/- 11.0 years), underwent full ophthalmologic examination and also retinal thickness analysis with RTA analyzer. In particular, foveola average thickness VAV, foveal average thickness FAV, peri foveal average thickness PFAV and posterior pole average thickness PPAV, were determined. The data were statistically evaluated and compared with those obtained for healthy subjects from the control group. RESULTS: The retinal thickness values in the populations of primary open-angle glaucoma and primary open-angle glaucoma-suspected patients were: VAV 139.0 +/- 20.5 microm i 147.6 +/ 21.2 microm, FAV 149.9 +/- 17.4 microm i 157.1 +/- 18.6 microm, PFAV 173.0 +/- 11.4 microm i 187.3 +/- 15.6 microm oraz PPAV 168.1 +/- 11.3 microm i 182.5 +/- 14.8 microm, respectively. Statistically significant differences between both populations and the population of healthy subjects were observed. CONCLUSIONS: The retinal thickness in macula region in primary open-angle glaucoma and in patients suspected of primary open-angle glaucoma was significantly lower than in the population of the healthy subjects. The method can be successfully applied in the early diagnosis of primary open angle glaucoma and be a valuable supplementary examination of the optic nerve disc and peripapillary area. PMID- 20572499 TI - [Analysis of rate, types and causes of uveitis in children hospitalized at Ophthalmology Clinic in Wroclaw in years 2001-2006]. AB - PURPOSE: The aim of the paper was to analyse frequency, causes and type of uveitis at children hospitalized in Ophthalmology Clinic of Medical Academy in Wroclaw in years 2001-2006. MATERIALS AND METHODS: Material from 64 (88 pairs) children's eyes was analyzed. There were 35 (54.7%) girls and 29 (45.3%) boys admitted to the Clinic with suspicion of uveitis. RESULTS: There were 17 (26.6%) children with uveitis anterior, 15 (23.4%) with pars planitis and 32 (50.0%) with uveitis posterior. The uveitis occurred in both eyes in 33.9%. Aetiology of uveitis was recognized at 30 (46.9%) patients, at 12 (16.6%) cases uveitis was related to systemic disease. At 22 (34.4%) ill children recognition of aetiology was not possible. The most often cause of uveitis anterior was juvenile chronic arthrosis inflammation and it occurred at 8 (47.1%) children--5 girls, and 3 boys. For the most patients 12 (80.0%), in case of pars planitis recognition of aetiology was impossible. Toxoplasmosis was the most often cause for uveitis posterior and it occurred at 14 (43.8%) children. CONCLUSIONS: Parasitic background is still considerable cause of uveitis among children. Juvenile chronic arthritis is the most often cause for uveitis anterior. In considerable amount of children cases, recognition of aetiology of uveitis was not possible. PMID- 20572500 TI - [The results of the treatment of the cataract in children and youth treated in Ophthalmology Clinic in Poznan]. AB - Cataract is a leading course of a treatable blindness and serious visual impairment in children. Treatment, especially in one-sided cataract is a challenge and it is connected with the risk of complications. The decision to perform a surgery in older children with already coexisting amblyopia is not easy to make. The aim of our study was to present the effects of the cataract treatment in children between 3 and 18 years old, in the Ophthalmology Clinic in Poznan. Between 2006 and 2008, the surgery was done in 36 children (42 eyes). The data of those patients, e.g. the type and location of the cataract, accompanying disorders and visual acuity reached, were analyzed. In this group of patient 60% of children reached visual acuity equal to 0.5, and 24% of them full visual acuity. The way to prepare the patient to the surgery, the way to calculate the power of the intraocular lens to be implanted and the surgery technique will be discussed. PMID- 20572501 TI - [Screening of selected parameters of visual system in children at the age of 6 to 10 in Great Poland area]. AB - PURPOSE: The goal of the work was to analyze parameters of visual system in children from Great Poland territory. Research covered: visual acuity and phoria at distance, stereo near vision, colour vision, near point of convergence, plus lens test. MATERIAL AND METHODS: 1138 children at the age of 6-10 years were examined, including 88 students in their spectacles. During the examination C Landolt plates, +1.00 lens, Titmus Stereo Fly test, Ishihara plates, fixation ball and Maddox rod were used. RESULTS: At least 70% children passed particular tests, but the whole examination was passed by only 40% children (in glasses 45% and 15%, respectively); among children who failed plus lens test, 36% did not pass stereotest; 12% of children (35% in glasses), failed stereotest and reached different visual acuity in both eyes, which can cause binocular dysfunction. CONCLUSIONS: It is necessary to expand the scope of the school vision screening in school children using additional parameters connected with far and near vision and binocular vision. PMID- 20572502 TI - [Temperament evaluation of patients with central serous retinopathy, preliminary report]. AB - PURPOSE: To assess differences in temperament in patients with central serous retinopathy and healthy subjects. MATERIAL AND METHODS: 20 patients diagnosed with acute central serous retinopathy was put to the questionnaire: Cloninger's Temperament and Character Inventory. RESULTS: Lower scores in novelty seeking (NS) (t = -2.43; p < 0.05) scale and its NS2 (t = -2.12; p < 0.05), and NS3 (t = 2.66; p < 0.05) subscales, as well as higher scores in harm avoidance HA4 subscale in CSR patients, were found. CONCLUSIONS: There is a different profile, regarding temperament and character in patients with central serous retinopathy, as compared to healthy subjects. PMID- 20572503 TI - [Neurofibromatosis type 1--own experiences]. AB - PURPOSE: Neurofibromatosis type 1 is one of the most common inherited syndromes. The aim of this study was to evaluate eye symptoms on this disease. MATERIAL AND METHODS: 52 patients with neurofibromatosis type 1 were observed (28 males and 24 females), age between 3 and 49 years old (mean 21). The patients were divided into five groups depending on the age: 0-10 years old, 11-20 years old, 21-30 years old, 31-40 years old and older than 40 years. Frequency of the eye symptoms was estimated in each group. RESULTS: The eye sings were observed in 69.2%. Frequency of the eye symptoms were higher in the older groups. After 21th years of age ophthalmological signs were observed in all patients. The most common were cafe-au-lait spots on the lids, Lisch nodules on the iris, changes in CNS, especially gliomas of the optic pathway, nodular neurofibromas in the orbit region. CONCLUSIONS: Eye signs of the disease may be noticed in the most patients with NF 1. After 21th years of age ophthalmological symptoms are observed in all patients. The frequency of typical well known for NF 1 signs were different and characteristic for each age group. PMID- 20572504 TI - Hidradenocarcinoma eccrinale syringomatodes of the eyelid--case of a rare malignancy. AB - PURPOSE: Presentation of a case of very rare malignant tumor of eccrine sweat glands in the eyelid. MATERIAL AND METHODS: A 44 years old man with a tumor of the upper left eyelid is presented. CONCLUSIONS: Sweat gland carcinomas are rare malignant tumors of the skin adnexa. Diagnosis of these carcinomas is difficult due to their infrequency. PMID- 20572505 TI - [Serpiginous choroidopathy--spectrum of fundus changes in 3 years of follow up]. AB - Serpiginous choroidopathy (SC) is classified as idiopathic chorioretinal disease. Atrophy of external retina comprising foveolar area and/or submacular neovascularisation is a leading cause of visual acuity deterioration. A case report shows progression of fundus lesion in the course of SC during 3 years of follow up. PMID- 20572506 TI - [Endophthalmitis following intravitreal triamcinolone acetonid injection--a case report]. AB - PURPOSE: To report a case of acute endophthalmitis following intravitreal triamcinolone acetonide injection. MATERIAL AND METHODS: A 54-year-old woman with diabetic macular edema developed endophthalmitis after triamcinolone injection. First she was treated with intravitreal antibiotic injections and next with four surgeries--facovitrectomy, revitrectomy, silicone oil removal and revitrectomy. RESULTS: The initial visual acuity was 0.5. From the vitreous cultured Staphylococcus epidermidis. Depite the intensive medical intervention, the toxic retinal damage occurred and the final visual acuity was hand movement. CONCLUSIONS: intravitreal triamcinolone injections can induce bacterial endophthalmitis, which has a devastating effect on the ocular tissues and results in severe loss of vision. The procedure of injection in diabetic and immunocompromised patients should be performed with great care. PMID- 20572507 TI - [Use of bevacizumab as an additional strategy in angle closure glaucoma--case report]. AB - We report the use of bevacizumab (Avastin) as an additional strategy in angle closure glaucoma based on the case of 47 years old male qualified to cataract removal as anti-glaucoma procedure, in whom we observed iris and lens neovascularization. As a first step we administered 1.25 mg of bevacizumab into the anterior chamber. Iris as well as lens neovasularization completely disappeared after 48 hours later. Finally after lens removal we achieved deeper anterior chamber, reduction and stabilization of intraocular pressure without necessity of administration hipotensive agents, and improvement of visual acuity. PMID- 20572508 TI - [Posterior ischemic optic neuropathy following bilateral radical dissection of cervical lymph nodes]. AB - Visual loss is a rare and potentially devastating complication of surgery under general anesthesia. We present a case of blindness after simultaneous bilateral neck dissection and discuss the perioperative circumstances and the possible causes. We also compare and contrast other such cases described in the literature and remind the clinical criteria for the diagnosis of perioperative type of posterior ischemic optic neuropathy. PMID- 20572509 TI - [Refractive laser eye surgery and binocular vision disorders--case report]. AB - Laser refractive surgery is a lively developing branch of ophthalmology. There are a numbers of contraindications for this type of surgery, but many of them are difficult to define, for example binocular vision impairment. Accurate analysis of orthoptic examination before refractive surgery, has forced us to dissuade our patient from refractive surgery, despite the fact that there were no other contraindications. CASE STUDY: A 33 years old woman referred for refractive surgery because of bilateral myopia (right eye: -5.25 Dsph -0.75 Dcyl ax. 170; left eye: -5.0 Dsph). There was no strabismus or other binocular vision disorders in her history. Orthoptic examination revealed exophoria, slight hyperphoria and considerable bilateral convergence insufficiency, which would have contributed to future strabismic complications. PMID- 20572510 TI - [Clinical characteristics of penetrating ocular injuries with intraocular foreign body. Part I. Pathogenesis and clinical features]. AB - Intraocular foreign bodies (IOFBs), are the major cause of penetrating ocular trauma and the most serious problem is the resulting impairment of visual function. In this paper, based on published reports and their clinical experience, authors discuss questions of pathogenesis, epidemiology and clinical features of IOFB injuries. Special attention was paid on primary and secondary complications, which include mechanical lesions of the ocular tissues, metallosis and endophthalmitis. PMID- 20572512 TI - [The psychological consequences of amblyopia]. AB - This is the review of references about problem of amblyopia and its psychosocial effects on children being cured. The study emphasies the need for psychological approach to problems that trouble children wearing glasses, suffering from strabismus and being cured by occlusion. PMID- 20572511 TI - [Clinical characteristics of penetrating ocular injuries with intraocular foreign body. Part II. Diagnostics and treatment]. AB - Ocular trauma remains a major cause of blindness, particularly in the working-age population. Intraocular foreign bodies (IOFBs ), frequently accompany penetrating ocular injuries and can lead to increased ocular morbidity. In this paper, based on published reports and their authors clinical experience, we discuss questions of advantages and disadvantages of three imaging methods (radiology, ultrasound and tomography), and evaluate the value of these methods in the diagnosis of IOFBs. Authors discuss also management options in patients with IOFB injuries and describe techniques of primary surgical repair and foreign body removal, especially pars plana vitrectomy. PMID- 20572513 TI - Private duty home care: a reflection on the industry. PMID- 20572514 TI - The battle for recruiting and retaining the best: are you up for the challenge? AB - In Dallas-Ft. Worth, TX, over 800 home care agencies compete for business--and employees - from seemingly every street corner. Among all those agencies, one of them, Haven Home Health, LLC, was named one of the area's small company "Best Places to Work" by the Dallas Business Journal. With the continuing shortages of home care professionals like nurses, aides, and therapists and struggles to recruit and retain talented, engaged employees in this industry, here's a look at what Haven's been doing, including some innovative employee programs, and why its team says it's one of the best places to work. PMID- 20572515 TI - Stepping out of the standard caregiving box: creative caregiving for the in-home care agency. PMID- 20572516 TI - Educating the public to plan ahead for private care needs. PMID- 20572517 TI - Care at home...wherever 'home' is. PMID- 20572518 TI - Home health payment rates and the Medicare cost report: we did it to ourselves and it's happening again. PMID- 20572519 TI - If service were a hymn. PMID- 20572521 TI - Caring: the key to employee retention. PMID- 20572520 TI - The shiver effect. PMID- 20572522 TI - Move over, George Foreman. PMID- 20572523 TI - Article on formocresol is 'misleading'. PMID- 20572524 TI - Dr. Congeniality. PMID- 20572525 TI - iDentistry--recent advances within the digital restorative arena. PMID- 20572526 TI - Dentistry a la carte: in-office CAD/CAM technology. AB - This article examines the differences among four in-office computer-aided design/computer-aided manufacturing restorative technologies. Two acquisition media systems, 3M ESPE's Lava COS and Cadent's iTero, are compared and contrasted. Additionally, two acquisition and manufacturing media, Sirona's CEREC AC and D4D's E4D, are examined. Image acquisition techniques and cast fabrication methodologies are compared between Lava COS and iTero. In addition, image acquisition, cast fabrication, and restoration fabrication methodologies are discussed as related to CEREC AC and E4D. Strategies for computer-aided design/computer-aided manufacturing incorporation into practice are explored. PMID- 20572527 TI - CAD/CAM options in dental implant treatment planning. AB - Several software platforms are available that use computerized tomography files and proprietary 3-D reformatting to aid in diagnosis, plan implant location, and complete the surgical placement and restoration of dental implants. This article will review traditional versus computerized model of surgical planning, advantages and disadvantages of computer-aided design/computer-aided manufacturing planning, variability in treatment sequence, and a cost analysis of investment into this treatment modality. PMID- 20572528 TI - Implementation strategies for incorporating new technologies into the dental practice. AB - Staying ahead of the technology curve is an ongoing challenge for all dentists. Ignoring advancements in technology and the related improvements in diagnostics and delivery of care, as well as the impact technology may have on productivity in practice, is simply not an option for the modern clinician who aims to maintain a successful contemporary practice. This article delivers some insight into the challenges that arise when upgrades in technology and the related acquisition investment are considered. PMID- 20572529 TI - Pemphigus vulgaris with significant periodontal findings: a case report. AB - The purpose of this article is to report a case of pemphigus vulgaris associated with periodontitis (plaque-induced inflammation), and the role of a dermatologist and a periodontist in its management. This case reaffirms the fact that plaque control is the most important procedure in preventing periodontal infection in pemphigus vulgaris patients. These patients should be informed about the risk of periodontitis and encouraged to pursue long-term periodontal follow up to prevent their periodontal disease progression. PMID- 20572530 TI - The rusty iron years. PMID- 20572531 TI - Finding the right way to die. PMID- 20572532 TI - U.S. nurses influence health care reform. PMID- 20572534 TI - Harnessing national parks for health. PMID- 20572535 TI - The Kaiwhakahaere comments. PMID- 20572537 TI - Nurses share their views on end-of-life issues. PMID- 20572538 TI - Providing intensive care. Interview by Teresa O'Connor. PMID- 20572539 TI - An unlikely nurse ponders palliative care. Interview by Teresa O'Connor. PMID- 20572540 TI - Administering the influenza vaccine. PMID- 20572541 TI - Reaching younger, at-risk people. PMID- 20572542 TI - Strenghtening the health and resilience of Whanau. PMID- 20572543 TI - It's your choice. PMID- 20572545 TI - Enrolled nurses are disappearing, but is a replacement in the wings? PMID- 20572546 TI - Injection of support. AB - The number of children arriving in A&E departments with ketoacidosis is rising and more nurse specialists are needed to help families and schools manage diabetes. PMID- 20572547 TI - Community rescue. Interview by Lynne Pearce. AB - One primary care trust has tackled the shortfall in health visitors and completely overhauled children's services. PMID- 20572549 TI - The cost of caring. PMID- 20572548 TI - Joint approach to arthritis care. Interview by Carol Davis. AB - A major study comparing nurse-led and doctor-led care for patients with rheumatoid arthritis is under way. PMID- 20572550 TI - A different road to recovery. PMID- 20572551 TI - Appearances can be deceptive with a post-operative patient. PMID- 20572552 TI - Medicines management. PMID- 20572553 TI - Nursing in prisons: developing the specialty of offender health care. AB - This article, the first in a five-part series, examines offender health care as a specialty. It explores the role of the nurse and the developments that have occurred over the last ten years in this field. In later articles, the authors discuss leadership skills for nurses working in the criminal justice system, assessment of the acutely ill patient, management of long-term conditions, and the future of nursing in offender health care. PMID- 20572554 TI - Graduate-only pre-registration mental health nursing programmes. AB - This article examines the perceived benefits of graduate-only pre-registration programmes in mental health nursing, and the potential social aspiration and attrition problems that may result. A number of strategies are identified to assist student integration into higher education and minimise any increase in attrition rates. PMID- 20572555 TI - An overview of sedation for adult patients in hospital. AB - Sedatives may be administered to patients in the hospital setting to provide comfort and reduce anxiety and pain. A variety of sedative agents can be used depending on the circumstances and the type of sedation required. This article provides an overview of the different levels of sedation, the most common pharmacological agents, used and the potential side effects and complications. The importance of patient assessment is emphasised. PMID- 20572556 TI - Complex health needs. PMID- 20572557 TI - The route to success. PMID- 20572558 TI - Respect for religious views. Interview by Sidone Chilufya. PMID- 20572559 TI - Medicine's magicians. PMID- 20572560 TI - Parkinson's disease. Bicycle therapy. PMID- 20572561 TI - Deep-brain stimulation. Wired well. PMID- 20572562 TI - The MS Lesion Project. PMID- 20572563 TI - The aging brain. Getting with the program. PMID- 20572564 TI - Litmus for reform. PMID- 20572565 TI - Living laboratory. PMID- 20572567 TI - Can the states nullify health care reform? PMID- 20572566 TI - A neurologist's legacy. How A.B. Baker helped make Minnesota a national player in neurology. PMID- 20572568 TI - The constitutionality of the individual mandate for health insurance. PMID- 20572569 TI - Migraine update. Diagnosis and treatment. AB - Migraine is a common intermittently debilitating neurovascular disorder that affects younger adults, especially women. The diagnosis is generally made based on clinical criteria, with neuroimaging used in some cases to exclude secondary causes of headache. This article reviews current understanding of the mechanisms underlying migraine and approaches to treating it. PMID- 20572571 TI - Caring for the patient with seizures. A 21st century approach. AB - Epilepsy is a condition that affects less than 2 percent of the population. In the past, people with recurring seizures often suffered their entire lives. Today, most seizure cases can be controlled with appropriate medication and follow-up. However, some patients require specialized care. This article reviews the current approach to diagnosing and treating epilepsy, which is based on the goals and standards set by the American Academy of Neurology. PMID- 20572570 TI - Myofascial trigger points. What physicians should know about these neurological imitators. AB - Myofascial trigger points (MFTPs) are a common cause of chronic neck and back pain.They also can cause a wide spectrum of associated symptoms.This review focuses on neurological symptoms--headache, dizziness, and sensory disturbances- that are frequently caused by musculoskeletal MFTPs. The discussion considers the diagnosis, pathophysiology, and treatment of MFTPs as well as the proposed mechanisms that generate the neurological symptoms. Physicians should consider these neurological imitators in patients who have such symptoms with no apparent cause. PMID- 20572572 TI - Rectal cancer multidisciplinary treatment: evidences, consensus and perspectives. PMID- 20572573 TI - Role of somatostatin analogs in the management of neuroendocrine tumors. AB - Neuroendocrine tumors are rare neoplasms. During the last two decades, somatostatin analogs, exerting their activity through both receptor binding and enzymatic inhibition mechanisms, have been a key option in the management of neuroendocrine tumors. The treatment of neuroendocrine tumors with high doses of somatostatin analogs determined high rates of tumor stabilization, but the dose response of somatostatin analogs on symptomatic relief and stabilization of tumor growth remains unpredictable. Several studies have indicated a higher efficacy of somatostatin analogs in well-differentiated, low-grade malignancy tumors that express a high density of somatostatin receptors. Synthesis of new, more effective molecules, with different pharmacokinetic profiles, receptor affinity and binding stability, will ease the clinician's tasks and improve patient expectancies in terms of survival and quality of life. Further studies are needed to clarify mechanisms underlying the better antiproliferative effect of higher doses of somatostatin analogs and to determine the optimum dose to saturate specific receptor subtypes. PMID- 20572574 TI - Interval cancers in breast cancer screening: comparison of stage and biological characteristics with screen-detected cancers or incident cancers in the absence of screening. AB - AIMS AND BACKGROUND: To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen detected cancers and "clinical" cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry. METHODS AND STUDY DESIGN: Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67). RESULTS: We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P=106), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10(-6)), pN (P = 10(-6)), grading (P = 10(-6)), estrogen receptors (P = 10(-5)), progesterone receptors (P = 10(-6)), and Ki67 (P = 10(-6)). CONCLUSIONS: Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis. PMID- 20572575 TI - Cancer mortality in Cordoba, Argentina, 1986-2006: an age-period-cohort analysis. AB - AIMS AND BACKGROUND: Cancer is the second main cause of death in Argentina, surpassed only by cardiovascular disease. However, analytical approaches isolating some of the known effects, such as age at death, period of death and birth cohort, have never been performed in cancer mortality studies in Argentina. The aim of this study was to analyze cancer mortality trends in a representative region of the country, the Cordoba province (1986-2006). METHODS AND STUDY DESIGN: Overall age-standardized (world population) mortality rates for cancer (all sites) were computed by a direct method. Joinpoint regression was fitted to the age-standardized mortality rates for both sexes to provide estimated and 95% confidence intervals of the annual percentage changes. The effects of age (15 age groups), period of death (1986-90, 1991-95, 1996-00 or 2001-06), and birth cohort (18 overlapping 10-year birth cohorts) covariates on mortality rates were estimated using a sequentially fitted Poisson regression model. RESULTS: During the study period, 102,737 people died of cancer in Cordoba, with the age standardized mortality rates decreasing from 139.3 to 118.7/100,000 person-years. Although this reduction was more noticeable in men, the joinpoint regression model showed a significant change of the age-standardized mortality rates after 1996 in both sexes. Age-period-cohort analysis suggested that the cancer mortality trends may be linked with a strong age effect and a moderate or mild period and cohort effect, related to sex and place of residence. CONCLUSIONS: Based on the observed cohort effect, it may be argued that there has been a lower exposure level to some risk factors, such as diet and other environmental factors, in Cordoba over the last decades. PMID- 20572576 TI - Vincristine, doxorubicin, cyclophosfamide, actinomycin D, ifosfamide, and etoposide in adult and pediatric patients with nonmetastatic Ewing sarcoma. Final results of a monoinstitutional study. AB - AIMS AND BACKGROUND: To investigate a six-drug combination in patients with nonmetastatic Ewing sarcoma, focusing on chemotherapy-induced necrosis and chemotherapy toxicity in adult and pediatric patients. METHODS AND STUDY DESIGN: Alternating cycles of vincristine (1.5 mg/m2), doxorubicin (80 mg/m2) and cyclophosfamide (1200 mg/m2) (weeks 0, 6, 13, 22 and 31), ifosfamide (9 g/m2), vincristine (1.5 mg/m2), and actinomycin D (1.5 mg/m2) (weeks 3, 16, 25 and 34), and ifosfamide (9 g/m2) and etoposide (450 mg/m2) (weeks 9, 19, 28 and 37) were administered. Primary chemotherapy-induced necrosis was graded: G3 (complete necrosis), G2 (microfoci of tumor cells) and G1 (macrofoci of tumor cells). RESULTS: From 1996 to 1999, 50 patients with Ewing sarcoma were enrolled. The median age was 23.5 years (range, 4-56). Chemotherapy-induced necrosis (in 28 patients) was G3 in 36%, G2 in 21% and G1 in 43%. At a median follow-up of 110 months (range, 36-129), 5-year overall survival and event-free survival were 72% and 66%, respectively. According to histologic response, 5-year event-free survival was 90% in G3, 83% in G2, and 42% in G1 (P = 0.02). In adult and pediatric (<18 years) patients, the incidence of G4 leukopenia was 62% and 74%, respectively, with febrile neutropenia in 13% and 21%, respectively. G4 thrombocytopenia occurred in 3% of cycles in adults and in 7% in pediatric patients. Platelet and red blood cell transfusions were required respectively in 1% and 11% of cycles in adults and in 6% and 24% of cycles in pediatric patients. CONCLUSIONS: The six-drug combination can be administered safely in adult and pediatric populations. About 40% of patients have a poor chemotherapy-induced tumor necrosis, leading to poor probability of survival. New strategies are recommended to improve survival of poor responders to the six-drug combination. PMID- 20572577 TI - Management of patients with gastrointestinal stromal tumor in clinical practice in Italy: a critical "event tree model" analysis of decision-making processes and outcomes. AB - AIMS AND BACKGROUND: Even though the standard treatment of patients affected by gastrointestinal stromal tumors has been well defined by clinical trials and clinical guidelines, in practice it may be different from those proposed in the literature. This paper reports and comments on a critical picture of the management of patients with gastrointestinal stromal tumors who received at least one treatment before arriving at our GIST Study Group. METHODS AND STUDY DESIGN: Attention was focused on 60 patients from various hospitals. Retrospective clinical data were recorded and analyzed with the "event tree" model, which describes the algorithm of all treatment options that each patient received before. Responses from first to fourth line of therapy, time to progression, and survival analysis were also analyzed. RESULTS: Starting from the diagnosis of disease, seven possible therapeutic event trees were identified: one for 7 unresectable patients and six different trees for 53 recurred patients who initially underwent surgery. The event trees describe the multitude of different treatments that patients with gastrointestinal stromal tumors received during the course of their disease. CONCLUSIONS: In clinical practice, the treatment of patients affected by gastrointestinal stromal tumor is still difficult, and the published recommendations often do not cover all therapeutic decisions for all clinical presentations of disease. Multidisciplinary dedicated teams are needed to offer the possibility to receive appropriate surgery and innovative medical therapies. The formation of formalized GIST Units is in progress in several parts of Italy. The GIST Units can be organized in a network to facilitate discussion and agreement for the wide variety of clinical presentation. PMID- 20572578 TI - Epirubicin and docetaxel as neoadjuvant treatment of locally advanced breast cancer: a phase II study. AB - AIMS AND BACKGROUND: Neoadjuvant chemotherapy is the standard treatment for locally advanced breast cancer. The combination of anthracyclines and taxanes is considered the first choice chemotherapy in advanced breast cancer. We report here the overall results of a phase II study of epirubicin and docetaxel as neoadjuvant chemotherapy in advanced breast cancer. PATIENTS AND METHODS: Forty five patients with locally advanced, nonmetastatic breast carcinoma were treated with epirubicin, 90 mg/m2, docetaxel, 75 mg/m2, intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery, followed by tamoxifen for 5 years if estrogen receptor positive and radiation therapy if indicated. Patient characteristics included a median age of 45 years; pre Ipostmenopausal, 311/14 patients; T3-T4 in 33, N0/N1 in 12/33; ductal/lobular in 42/3; ER+ in 23; and HER2 overexpression in 23. RESULTS: Clinical response included complete remission in 7 patients and partial remission in 27 (response rate, 75%). All 45 patients underwent surgery (quadrantectomy in 7). Histological examination of the breast and lymph nodes revealed no signs of disease in 3 patients and ductal carcinoma in situ only in 2. Twenty-five patients completed the chemotherapy program. G3-G4 toxicity included neutropenia in 39 patients. No other G3-4 toxicity nor toxic deaths occurred. Median relapse-free and overall survival were 35 and 56 months, respectively. CONCLUSIONS: The neoadjuvant treatment was active and well tolerated, but the incidence of pathologic complete remissions was relatively low. PMID- 20572579 TI - Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results. AB - AIMS AND BACKGROUND: There has been a trend to replace cisplatin with carboplatin in the treatment of small-cell lung carcinoma. The goal of the present study was to determine the efficacy of carboplatin and etoposide followed by thoracic radiotherapy in patients with previously untreated limited disease small-cell lung carcinoma. METHODS: From February 2001 to March 2007, 47 patients with limited disease small-cell lung cancer were enrolled in the study. Etoposide, 100 mg/m2, was administrated intravenously on days 1-3 in combination with carboplatin, AUC 6, on day 1 every 21 days for 6 cycles. In cases considered to have non-progressive disease following induction chemotherapy, thoracic radiotherapy was given with in a once daily fraction of 2.0 Gy, 5/wk, up to 50-60 Gy. RESULTS: Forty-one patients were evaluated. Median age was 62 (range, 40-78), 88% of patients were male. ECOG PS was 0-1 in 38 patients. Seven of the 41 patients (17.5%) had pleural effusion (one malignant) and 7 patients (17.5%) had involved supraclavicular lymph nodes. Ninety percent of patients had elevated serum lactate dehydrogenase levels. Median follow-up was 13.5 mo. A total of 209 cycles of chemotherapy was administered (median, 6; range, 1-6). Thoracic irradiation was given to 33 patients. The overall response rate to combined modality on an intention-to-treat basis was 73%. Median survival time was 13.7 months (95% CI, 10.3-17.1), and median progression-free survival was 9.5 months (95% CI, 8.6-10.4). Two- and four-year overall survival was 23% and 7%, respectively. Grade 3-4 neutropenia and leukopenia were the most common adverse events and occurred in 46.0% and 24.0% of the patients, respectively. Six (14%) patients experienced febrile neutropenia. Three patients (7%) died of sepsis and neutropenic fever. Non-hematological toxicities were mild. CONCLUSIONS: Carboplatin and etoposide chemotherapy followed by thoracic radiotherapy in LD SCLC appears to be unsatisfactory. PMID- 20572580 TI - Anti-androgen therapy suspension following prolonged clinical and biochemical response: outcomes in a series of elderly patients with advanced prostate cancer. AB - AIMS AND BACKGROUND: To describe the outcomes following the suspension of androgen-suppression therapy in a series of elderly patients in an advanced stage of prostate cancer and in prolonged clinical and biochemical response. MATERIAL AND METHODS: Of 371 consecutive patients with advanced prostate cancer and treated with androgen-suppression therapy, 44 older patients were defined as in stable response on the basis of the following: absence of noteworthy dysuria, normal prostate findings on digital rectal examination, and prostate-specific antigen values lower than 0.50 ng/ml. After suspending treatment, it was to be re scheduled in case of onset of dysuria, evidence of a palpable lesion on digital rectal examination, or a rise in prostate-specific antigen above 10 ng/ml. Progression of disease was defined as a prostate-specific antigen level increase at two subsequent measurements, and/or the appearance of new lesions, and/or evidence of progression of disease on digital rectal examination. RESULTS AND CONCLUSIONS: Median age of patients was 78.5 years at the moment of therapy suspension. After a median follow-up of 93.9 months, fourteen patients (31.8%) showed progression of disease, but only 7 (15.9%) of these died. In 7 (15.9%) patients, serum testosterone levels did not exceed 0.5 ng/ml, indicating an absence of gonadal activity. The median time to progression was 138.2 months, and the median cumulative survival from the start and from the suspension of androgen suppression therapy was 105.5 months and 64.1 months, respectively. The savings in drug costs amounted to 772,267 Euro. Taking into consideration these outcomes of survival and of savings in drug costs, we can conclude that in these selected elderly patients, this treatment option could be of interest. PMID- 20572581 TI - Radiotherapy alone or with concomitant daily low-dose carboplatin in locally advanced, unresectable head and neck cancer: definitive results of a phase III study with a follow-up period of up to ten years. AB - AIM AND BACKGROUND: Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. MATERIALS AND METHODS: From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. RESULTS: The 3, 5 and 10 year local-regional recurrence-free survival rates were better in arm II (21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs. 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). CONCLUSIONS: Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial. PMID- 20572582 TI - Comparison of radiotherapeutic management of operated breast cancer in 1999 and in 2006: a sampling survey on the southeast coast of China. AB - AIMS: To obtain a better understanding of the changes in radiotherapeutic management of breast cancer patients in the more developed areas of China over the past decade. METHODS: Four academic radiation therapy departments located on the Southeast Coast of China were selected for the study. The survey was conducted on female breast cancer patients who received radiotherapy in 1999 and 2006. The questionnaires were designed to determine the purposes of radiotherapy and to address the postoperative radiotherapy techniques used. The data for these two years were analyzed and compared. RESULTS: The percentage of breast conserving treatment increased from 3% in 1999 to 13% in 2006, but the percentage of patients treated with postmastectomy radiotherapy dropped from 69% in 1999 to 66% in 2006 (P < 0.05). As regards the changes in techniques from 1999 to 2006, the use of special immobilization devices, treatment planning systems, and CT simulations increased from 46% to 80%, 23% to 70%, and 0% to 14%, respectively (P <0.01). From 1999 to 2006, irradiation of the chest wall following mastectomy increased from 67% to 90%, but for internal mammary irradiation it decreased from 76% to 30% and for the axilla, from 69% to 37% (P < 0.01). There were no obvious differences between 1999 and 2006 on the field design, boost treatment on the tumor bed, or dose prescription. CONCLUSIONS: Breast-conserving treatment was performed more frequently in China in 2006 than in 1999, but postmastectomy radiotherapy did not change a great deal and it was still an essential option. Although the international treatment guidelines have been accepted and implemented by physicians in recent years, prompt improvement in the quality of breast cancer radiotherapy is needed. PMID- 20572583 TI - A preliminary audit experience of surgery for rectal cancer after neoadjuvant chemoradiation therapy. AB - AIMS AND BACKGROUND: A surgical audit is a systematic critical analysis of surgical performance, with the goal to improve the quality of patient care. Rectal cancer surgery is one of the most delicate procedures in the field of surgical oncology, with significant variations in terms of complications from center to center. Neoadjuvant chemoradiation therapy leads to a significant reduction in local recurrences in patients with locally advanced lower and medium rectal cancer. The aim of the study was to evaluate the influence of neoadjuvant chemoradiation therapy on postoperative morbidity and mortality in patients with rectal cancer. METHODS AND STUDY DESIGN: From January 1, 2003, to December 31, 2007, patients who underwent elective surgical resection for lower and medium rectal cancer in our Surgical Unit were prospectively analyzed. Patients (n=42) were divided into two groups: (1) those treated with neoadjuvant chemotherapy and consequent surgical resection (19/42); (2) those treated with primary surgical treatment (23/42). P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity) and CR-POSSUM (ColoRectal-POSSUM) scores were calculated for each patient group. Thirty-day mortality and morbidity rates were prospectively collected in a comprehensive data base. Data were evaluated by comparing the predictions of the two scoring systems in both study groups with clinically observed mortality and morbidity rates. RESULTS: In group 1, no death was registered (0/19). The P-POSSUM and CR-POSSUM expected mortality was 2.43% and 4.52%, respectively (P > 0.05). In group 2, a single death was documented (1/23, 4.35%). The P-POSSUM and CR-POSSUM expected mortality was 2.1% and 4.94%, respectively. The postoperative complications rate for group 1 was 10.52% (2/19) compared to 34.88% as expected from the P-POSSUM score (P < 0.05). In group 2, a postoperative complication rate of 39.13% (9/23) was observed compared to 34.26% as expected from the P-POSSUM score (P > 0.05). CONCLUSIONS: No significant influence on morbidity or mortality was detected in patients who underwent neoadjuvant radio-chemotherapy. PMID- 20572584 TI - Male breast lesions: which abnormalities really need core needle biopsy? AB - AIMS AND BACKGROUND: The purpose of the study was to identify clinical, mammographic or sonographic abnormalities of the male breast that require histological characterization. METHODS AND STUDY DESIGN: Clinical and imaging features of 31 male patients with breast lesions were retrospectively evaluated and correlated with core needle biopsy results. RESULTS: Seven of 31 (22.6%) lesions proved to be malignant and 24 of 31 (77.4%) benign, with a benign/malignant ratio of 4.4:1. In the case of a suspicious clinical presentation (firm mass, nipple retraction) and/or the presence of risk factors for breast cancer (BRCA2 mutation, previous breast cancer), core needle biopsy always demonstrated malignancy. All malignant lesions identified on mammography (4 of 7) appeared as a mass. Benign lesions detected on mammography (21 of 24) presented as an area of increased density (20 of 21) more frequently than a mass (1 of 21). CONCLUSIONS: Sonographic features of cancers were not different from those of benign lesions. Clinical and mammographic findings, along with patient history, can be useful in the identification of male breast lesions that require core needle biopsy. PMID- 20572585 TI - The effectiveness of a scalp cooling cap in preventing chemotherapy-induced alopecia. AB - AIMS AND BACKGROUND: Hair loss is one of the most unpleasant side effects associated with chemotherapy treatments. It causes emotional disturbances and constantly reminds the patient of the disease. This study analyzed the effectiveness of scalp cooling caps in preventing alopecia among 64 patients. METHODS: The patients were given one of the following chemotherapeutic treatments: doxorubicin 60 mg/m2, docetaxel 80 mg/m2, FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) or the combination of three cycles of docetaxel (80 mg/m2) followed by three cycles of FEC (5 fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). All the chemotherapy treatments were given in a three-weekly schedule. Patients with early stage disease were given six adjuvant chemotherapy cycles, while patients with metastatic disease were given nine chemotherapy cycles. The patients were provided with detailed instructions on how to treat the hair at home for one to three days after the chemotherapy treatment. Hair loss was evaluated after the third, sixth and final treatments. RESULTS: In the final results, major hair loss was avoided in all patients given doxorubicin treatment, in 83.3% of patients given docetaxel treatment, in 76.5% of patients given FEC treatment, and in 78% of patients given docetaxel followed by FEC. In the final evaluation, 87.5% of the patients considered the avoidance of hair loss to be important. Only 20.3% of the patients needed to use a wig. CONCLUSIONS: This study shows that all the patient groups studied gained some benefit by using scalp cooling caps. PMID- 20572586 TI - The revised piper fatigue scale (PFS-R) for Italian cancer patients: a validation study. AB - BACKGROUND AND AIM: Fatigue is one of the most frequently reported symptoms by cancer patients. In recent years, much effort has been directed to designing fatigue measures which are psychometrically appropriate as well as easily administered. Among these, the Revised Piper Fatigue Scale (PFS-R) is widely used in assessing fatigue in cancer patients and other populations. Despite its large utilization in different national contexts and with different populations, its structure appears to vary across cultures, suggesting the need for its validation before use. The main aim of the present work was to verify the validity (i.e., dimensional structure and construct validity) and reliability (i.e., internal consistency) of an Italian translation of the PFS-R to reassure Italian oncology practitioners about its appropriate usage in practice and research. METHODS AND STUDY DESIGN: One-hundred ten Italian oncological inpatients were administered an Italian translation of the PFS-R together with a form for the collection of personal identification and clinical data and other fatigue and quality of life measures (POMS and EORTC QLQ-C30) already validated for Italy. RESULTS: Principal component exploratory factor analysis revealed a four-factor structure quite similar to (although not overlapping) the original described by Piper and colleagues; all four factors proved to be reliable and to correlate with one another and with previous validated measures of fatigue and quality of life. Preliminary descriptive statistics were also provided for data comparisons. CONCLUSIONS: Despite the discussed limitations, PFS-R seems a valid and reliable multidimensional fatigue measure also adequate in Italian oncological settings. PMID- 20572587 TI - Influence of recombinant human growth hormone (rhGH) on proliferation of hepatocellular carcinoma cells with positive and negative growth hormone receptors in vitro. AB - AIMS AND BACKGROUND: Recombinant human growth hormone (rhGH) is increasingly used in the clinic because it promotes the synthesis of proteins. However, rhGH is able to increase malignant transformation and tumor recurrence. The aim of this study was to investigate the effects of rhGH on hepatocellular carcinoma (HCC) cells with positive and negative growth hormone receptors (GHR) in order to guide its clinical application. METHODS AND STUDY DESIGN: Cells of the human HCC cell lines Bel-7402 (GHR+) and SMMC-7721 (GHR-) as well as human umbilical vein endothelial cell line ECV304 cells in the exponential growth phase were harvested and divided into experimental and control groups. After the human HCC cells were cultured alone or co-cultured with ECV304 cells under the different treatments, cell cycle phase, proliferation index, and expression levels of vascular endothelial growth factor (VEGF) mRNA and proteins were determined. RESULTS: In the Bel-7402 GHR+ cells treated with rhGH, both the percentage of cell in G2-M phase and the proliferation index were higher than those of controls (P < 0.05); this was not the case in the SMMC-7721 GHR- cells treated with rhGH (P > 0.05). Although there was no difference in the cell doubling times between ECV304 cells co-incubated with Bel-7721 GHR-cells treated with rhGH and without rhGH, the doubling times of ECV304 cells co-incubated with Bel-7402 GHR+ cells, when treated with rhGH, were significantly shortened compared to those of controls (P < 0.05). The cell doubling times of ECV304 cells co-incubated with Bel-7721 GHR- or Bel-7402 GHR+ cells which were treated with bevacizumab were longer than those of controls and of cells with rhGH (P < 0.05). The VEGF mRNA and protein expression levels were higher in Bel-7402 GHR+ cells treated with different doses of rhGH than controls (P < 0.05 or P < 0.01); however, there was no statistically significant difference in the expression levels of VEGF mRNA and proteins between SMMC-7721 GHR- cells treated with rhGH and controls. CONCLUSIONS: rhGH can induce VEGF secretion and stimulate proliferation of Bel-7402 GHR+ cells in vitro, but has little effect on the proliferation of SMMC-7721 GHR-cells, suggesting that rhGH may be applied safely to treatment for the catabolic state in patients with GHR-negative HCC. PMID- 20572588 TI - Knockdown of TSPAN1 by RNA silencing and antisense technique inhibits proliferation and infiltration of human skin squamous carcinoma cells. AB - AIM: To explore the function ofTSPAN1 in squamous cell skin carcinoma by means of TSPAN1-specific siRNA and antisense oligonucleotide techniques. METHODS: pU6H1 GFP-siRNA TSPAN1 and pcDNA3.1 antisense TSPAN1 were constructed and transfected into squamous cell skin carcinoma cell line A431 cells to knock down TSPAN1 gene expression. The levels of TSPAN1 mRNA and protein expression were detected by semiquantitive RT-PCR and Western blot, respectively. The proliferation rates of A431 cells were determined by MTT assay and flow cytometry. Lastly, the migration and infiltration of A431 cells were determined by the Transwell migration assay. RESULTS: Transfection with either pU6H1-GFP-siRNA TSPAN1 or pcDNA3.1 antisense TSPAN1 led to an obvious reduction of expression levels of TSPAN1 mRNA and protein in A431 cells, respectively. The proliferation, migration and infiltration of A431 cancer cells were significantly inhibited at 48 hours after transfection of plasmids harboring TSPAN1 siRNA and antisense RNA. CONCLUSION: The TSPAN1 gene might play a role in the proliferation of squamous cell carcinoma of the skin and be associated with cancer cell motility, implying a function of the gene in the development of skin cancer. PMID- 20572590 TI - Expression analysis of Wnt-5a in renal epithelial neoplasms: distinguishing renal oncocytoma from a wide spectrum of renal cell carcinomas. AB - OBJECTIVE: To study the expression of a novel marker, Wnt-5a, in renal epithelial neoplasms and determine its clinicopathological significance. METHODS: Immunohistochemical analysis of Wnt-5a was carried out in normal human kidney samples as well as in 123 primary renal epithelial neoplasms including 37 clear cell renal cell carcinomas (RCCs), 24 papillary RCCs (15 type 1 and 9 type 2), 25 chromophobe RCCs, 11 Xp11 translocation carcinomas, 6 mucinous tubular and spindle cell carcinomas, and 20 oncocytomas. RESULTS: Wnt-5a was expressed in 18.9% (7/37) of clear cell RCCs, 12.5% (3/24) of papillary RCCs, 16% (4/25) of chromophobe RCCs, 18.2% (2/11) of Xp11 translocation carcinomas, 0% (0/6) of mucinous tubular and spindle cell carcinomas, and 100% (20/20) of oncocytomas. There was a significant difference in Wnt-5a immunohistochemistry between renal oncocytoma and the other subtypes of RCC (P < 0.01). CONCLUSIONS: Our results indicate that Wnt-5a is a potentially useful immunohistochemical marker for the complex differential diagnosis between oncocytoma and other subtypes of RCC and also suggest that Wnt-5a may be a tumor suppressor gene in RCC. PMID- 20572589 TI - Attenuated Salmonella typhimurium carrying TRAIL and VP3 genes inhibits the growth of gastric cancer cells in vitro and in vivo. AB - BACKGROUND: Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and apoptin (VP3) of chicken anemia virus can selectively induce apoptosis in human tumor cell lines by two different pathways. Salmonella not only delivers functional genes to mammalian cells but also possesses antitumor activity and therefore could be adopted as a novel vector for anticancer therapy. MATERIALS AND METHODS: TRAIL and VP3 genes were cloned into a pBudCE4.1 vector and delivered by attenuated Salmonella typhimurium into gastric cancer cells, and their expression and antitumor effects in nude mice were monitored by Western blot, fluorescence microscopy, MTT assay, TUNEL staining, and immunohistochemistry. RESULTS: pBud-VP3 and pBud-TRAIL-VP3 plasmids were constructed to express TRAIL and apoptin in gastric cancer cells, leading to inhibition of cancer cell proliferation after 48 hours (P < 0.05). TRAIL and VP3 genes in pBudCE4.1 vector were also successfully delivered by attenuated S. typhimurium into gastric cancer cells in vivo, in which both TRAIL and apoptin were expressed. In vivo data indicated that S. typhimurium carring pBud-TRAIL-VP3 induced significant cell growth inhibition and tumor regression (P < 0.05). Moreover, expression of TRAIL and apoptin increased the expression of caspase-3 and caspase-9, resulting in enhanced apoptosis. CONCLUSION: Delivery of TRAIL and VP3 genes by attenuated S. typhimurium can significantly inhibit the growth of gastric cancer cells in vitro and in vivo. PMID- 20572591 TI - Overexpression of Smac/DIABLO in Hep-2 cell line: possible role in potentiating the sensitivity of chemotherapeutic drugs. AB - AIMS AND BACKGROUND: The major obstacles for tumor chemotherapy are drug resistance and/or adverse effects on the host. In the present study we investigated the role of the second mitochondria-derived activator of caspase (Smac/DIABLO) in the action of cisplatin (DDP), 5-fluorouracil (5-FU), and the combination of both in Hep-2 cells. METHODS AND STUDY DESIGN: Hep-2 laryngeal carcinoma cells exposed to DDP, 5-FU and the combination of both were investigated. Cell viability was determined by MTT assay. Apoptosis was measured by Ho.33342 and PI double staining and flow cytometry. The expression of Smac/DIABLO at the mRNA and protein level was assayed by RT-PCR and Western blotting. RESULTS: DDP, 5-FU and the combination of both drugs reduced the cell survival rates in a concentration- and time-dependent manner. The drug combination not only exerted a stronger inhibitory effect, but also at a lower concentration compared with the single drugs. Apoptosis was concomitant in a caspase-dependent manner. The expression of Smac/DIABLO increased significantly at both mRNA and protein levels after cell exposure to the combination compared with single drugs. CONCLUSIONS: Smac/DIABLO plays a pivotal role in attaining a synergistic effect in Hep-2 cells in response to this combined strategy. PMID- 20572592 TI - Optimizing craniospinal radiotherapy delivery in a pediatric patient affected by supratentorial PNET: a case report. AB - New advances in radiation therapy for children allow increased conformability and reduced doses to non-target tissues. We report our experience in treating a 4 year-old child with craniospinal tomotherapy after surgery of the primary tumor, a supratentorial primitive neuroectodermal tumor. The tomotherapy plan was compared with conventional craniospinal irradiation, 3D conformal radiation therapy, and intensity-modulated radiation therapy plans. The possible disadvantages of tomotherapy related to the radiation dose to organs at risk, treatment planning, and anesthesia should be carefully considered as the use of the technique is not suggested in a general manner, but selectively, in critical pediatric radiotherapy cases. PMID- 20572593 TI - Inflammatory pseudotumor of mediastinum treated with tomotherapy and monitored with FDG-PET/CT: case report and literature review. AB - Mediastinal inflammatory pseudotumor is a rare disease with reactive pseudoneo plastic features and a proven capacity for local invasion. The radiographic appearance of inflammatory pseudotumor is quite non-specific and the definitive diagnosis is based on the histological evaluation of tissue specimens. Resection of the lesion is the treatment of choice. However, nonsurgical treatments such as radiotherapy and steroids have been employed in the setting of incomplete surgical resection, tumor recurrence, and patients being unfit for surgery. The case described here is being reported because of the rare mediastinal location and atypical treatment approach including salvage irradiation and monitoring with FDG-PET/CT. Because of the irregular target volume inside the mediastinum as defined by FDG-PET/CT and the significant pulmonary comorbidity, it was deemed necessary to optimize dose delivery with intensity-modulated radiation therapy (IMRT). A possible gain by means of daily control of patient setup with image guided radiation therapy was also hypothesized and we used tomotherapy to irradiate the lesion. The first FDG-PET/CT after treatment confirmed further reduction of the metabolic activity followed by stable disease in the mediastinum, with no new occurrence of disease 16, 24 and 30 months after tomotherapy. PMID- 20572594 TI - A case of relapsed medulloblastoma treated with intensity-modulated radiotherapy and temozolomide. AB - We report a case of relapsed high-risk non-metastatic medulloblastoma in a 14 year-old boy, which was treated with intensity-modulated radiotherapy (IMRT) and temozolomide (TMZ). At the age of 11, the patient underwent an MRI-confirmed incomplete resection of a fourth-ventricle medulloblastoma, followed by conventional chemotherapy, craniospinal irradiation (55.8 Gy, 1.8 Gy/fraction) and then myeloablative chemotherapy followed by peripheral blood progenitor cell rescue. After 18 months of complete remission following the completion of chemotherapy, MRI showed a 2.5-cm mass in the olfactory notch. The patient underwent IMRT (45 Gy, 1.8 Gy/fraction) with concomitant administration of TMZ (180 mg/m2, 5 days every 21 days), which was well tolerated. After 5 cycles of TMZ, MRI showed complete remission with no evidence of the mass. TMZ was continued for another 5 cycles and then stopped. At 14 months from the completion of IMRT, a new MRI scan showed multiple nodular relapses around the fourth ventricle and the patient is currently treated with oral etoposide. PMID- 20572595 TI - Mesenteric cyst: report of a case-resulting in pseudomyxoma peritonei. AB - BACKGROUND: A mesenteric cyst may have an embryonic, traumatic, neoplastic or infectious origin. In rare cases mesenteric cysts may contain neoplastic epithelium. A mesenteric cyst has not previously been recorded as the cause of pseudomyxoma peritonei. METHODS: A patient who developed widespread mucinous intraperitoneal tumor as a result of a ruptured mesenteric cyst is reported. A literature review of the clinical features, diagnosis, treatment, and prognosis of the mesenteric cyst is presented. RESULTS: This patient was treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Her recovery was uneventful and she remains well two years after treatment. CONCLUSION: Mesenteric cyst is a rare cause of pseudomyxoma peritonei. The definite treatment of a ruptured neoplastic mesenteric cyst can, by analogy, be compared to the treatment for pseudomyxoma peritonei of appendiceal origin. The results of cytoreductive surgery with perioperative intraperitoneal chemotherapy are expected to be good. PMID- 20572596 TI - Paclitaxel and carboplatin-induced complete remission in peritoneal carcinomatosis of unknown origin: a report of two cases and review of the literature. AB - Peritoneal carcinomatosis is a common evolution of digestive-tract cancer with a poor prognosis. However, a small subgroup unrelated to the digestive tract or any other primary cancer has a relatively better prognosis, especially in women. There are no published data to recommend a treatment regimen for this distinct group. Here we present two women with peritoneal carcinomatosis of unknown origin, who responded to chemotherapy with paclitaxel plus carboplatin. One underwent an exploratory laparotomy and was confirmed to have no residual tumor. The other had complete resolution of ascites and omentum lesions confirmed by radiological examination. From this experience we propose that paclitaxel plus carboplatin is an effective combination regimen for this unique subset of patients. Further prospective trials should be conducted to substantiate this proposal in a larger patient cohort. PMID- 20572597 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in a patient with peritoneal mesothelioma and HIV infection. AB - BACKGROUND: High rates of septic complications have been associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, which has been suggested as the treatment of choice for isolated peritoneal malignancies. Patients infected by the human immunodeficiency virus (HIV) are still considered at a high operative risk. METHOD: A 58-year-old man with HIV infection and diffuse peritoneal mesothelioma underwent optimal cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. RESULTS: The patient experienced a complete clinical response to therapy with no adverse effect on disease course or markers for HIV (CD4 count, beta2-microglobulin, neopterin, p24 antigen, and viral load). CONCLUSION: This report suggests that this innovative approach can be successfully performed also in this clinical setting. In selected patients who respond to all criteria, surgery is possible and is a safe and effective therapeutic option. PMID- 20572598 TI - Malignant mesenchymoma of the thyroid: case report and literature review. AB - Malignant mesenchymoma of the thyroid is extremely rare. We report such a tumor involving the bilateral lobes of the thyroid which showed simultaneous chondrosarcomatous, osteosarcomatous, fibrosarcomatous and rhabdomyosarcomatous differentiation. The patient was a 52-year-old woman admitted with a history of facial swelling, neck thickness and swallowing discomfort of one month's duration. Sonographic examination indicated a thyroid mass involving the bilateral lobes. Macroscopically, the tumors of both lobes were well demarcated, solid, greyish-white, and multinodular on the cut surface. Some nodules were translucent in appearance and hard in texture. Microscopically, the tumor was composed of small primitive mesenchymal cells with osteoid formation resembling the small cell variant of osteosarcoma interspersed with multiple cartilaginous nodules that indicated chondrosarcomatous differentiation. Some tumor cells showed prominent rhabdomyoblastic differentiation with eosinophilic cytoplasm and eccentric nuclei. Fibrosarcomatous areas were also observed. Immunohistochemically, the small primitive mesenchymal cells were positive for vimentin and CD99 and negative for CD56, Syn, CgA, CK, TG, TTF-1, calcitonin, and S-100. The tumor cells in the rhabdomyosarcomatous area were MyoD1 and muscle specific actin positive. Molecular analysis for BRAFand RAS gene alterations showed no point mutation. The tumor recurred four months after surgery and tumor thrombi were suspected in the bilateral internal carotid arteries on ultrasonography. Primary malignant mesenchymoma of the thyroid is a high-grade malignant tumor with a poor prognosis. Its differerential diagnosis includes anaplastic carcinoma and other rare sarcomas with chondroid, osteoid, and other mesenchymal metaplasia. PMID- 20572599 TI - Multiple proliferating trichilemmal tumors in a middle-aged yellow man. AB - Proliferating trichilemmal tumor (PTT) is a rare but morphologically distinctive tumor. It usually occurs on the scalp of elderly women, characterized by frequent local recurrence. Some authors have recently proposed to classify PTT among the squamous cell carcinomas. We present the case of a 47-year-old yellow man with a 20-year history of multiple benign tumors in a number of anatomic areas. Based on their histological features, the tumors were diagnosed as PPTs. The case is unusual for the sex and age of the patient and the tumor locations. Moreover, this report illustrates a rare tumor which can be diagnostically challenging. The differentiation between a benign or malignant process in these lesions can sometimes be difficult. Careful clinical and histological assessment is necessary for an accurate diagnosis. PMID- 20572600 TI - Meningeal carcinomatosis: an extremely rare involvement of urinary bladder carcinoma. AB - Meningeal carcinomatosis (MC) is a rare presentation of solid tumors, particularly breast cancer, lung cancer, and malignant melanoma. Recently, the incidence of MC has been reported to be increasing. It has a bad prognosis despite aggressive therapy. The usual clinical presentation is multifocal involvement of the neuraxis, with headache and radicular pain being the most common initial symptoms. The most frequent signs are motor deficits, altered mental status, and cranial nerve involvement. The treatment of MC remains controversial and no straightforward guidelines exist in the literature. MC from urinary bladder tumors is rare. In this case report, we present a 52-year-old male patient with meningeal metastasis from a primary urinary bladder carcinoma along with a review of the related literature. Free full text available at www.tumorionline.it PMID- 20572601 TI - A rare case of primary small bowel adenocarcinoma with intussusception. AB - Other than in childhood, intussusception is unusual and nearly always caused by a structural and well demonstrable lesion. In contrast with the colon tract, the incidence of primary malignancies in the small bowel is very low. We report the case of a 51-year-old man presenting with jejunal intussusception due to a primary adenocarcinoma. To our knowledge, only a few similar cases have been reported in the literature to date. The patient was referred to our division for bowel obstruction. A CT scan showed a jejunal intussusception and surgical exploration was hence considered. At laparotomy, jejunal intussusception located just after the ligament of Treitz due to a polypoid lesion was confirmed and resection of the first jejunal loop was carried out. Histological examination of the specimen resulted in a diagnosis of a primary adenocarcinoma of the small bowel. In adult intestinal intussusception, resection without reduction is considered the optimal management if an underlying primary malignancy cannot be excluded. PMID- 20572602 TI - CD138-positive plasmacytoid urothelial carcinoma of urinary bladder with focal micropapillary features. AB - Both the plasmacytoid and micropapillary types of urothelial carcinoma of the urinary bladder are uncommon, distinct clinical and pathological findings. To date, several reports in the English medical literature have been published on either of these variants. CD138 is commonly used as a marker for tumors of plasma cell origin. However, few authors have described positive immunoreactivity of plasmacytoid cells in urothelial carcinoma. Mixed histological differentiation is thought to be a phenotype of locally aggressive and advanced urothelial carcinoma. Therefore, a precise histopathological diagnosis should be made and awareness of all the entities is crucial. We report a case of CD138-positive plasmacytoid urothelial carcinoma of the bladder with focal micropapillary features. To our knowledge this is the first case of these two rare subtypes of urothelial carcinoma combined in a single cystectomy specimen. PMID- 20572604 TI - Birth in 2050. PMID- 20572603 TI - Renal cell carcinoma: incidence and cost estimation in the era of targeted therapy. PMID- 20572606 TI - Family planning and safe motherhood. PMID- 20572607 TI - A hidden tragedy: birth as a human rights issue in developing countries. PMID- 20572608 TI - The issue of birth rights. PMID- 20572609 TI - The International MotherBaby Childbirth Initiative: a human rights approach to optimal maternity care. PMID- 20572610 TI - Newborn group B strep infection. Top 10 reasons not to culture at 36 weeks. PMID- 20572611 TI - A matter of maternal malnutrition? Explaining stillbirth/neonatal death rates in developing nations. PMID- 20572612 TI - From hospital to home. PMID- 20572613 TI - Shedding light on maternal mortality. PMID- 20572614 TI - Full moon birthing. PMID- 20572615 TI - If I were the baby. Questioning the widespread use of synthetic oxytocin. PMID- 20572616 TI - The "miracle" of induction. PMID- 20572617 TI - Pushing through: a tale of homebirth after cesarean. PMID- 20572619 TI - Dear Rose. PMID- 20572618 TI - Medical progress in 2110? A parody. PMID- 20572620 TI - The dangers of planned hospital births. AB - Hospital birth* has not undergone rigorous scientific scrutiny, yet is commonly believed to be safer than planned homebirth, even for low-risk women. A commonly promoted notion is that there are rare complications, which can arise at birth, making a hospital birth safer for low-risk women. There is no published research to support this notion. Where trained and equipped birth attendants are available, and hospital transfer is closer than 30-45 minutes, a planned, attended homebirth is safer for low-risk women than a planned hospital birth. Currently available published research suggests planning a hospital birth is not safer than planning an attended homebirth for women with one head-down fetus, between 37-42 weeks, no high blood pressure, no previous cesareans and no serious medical conditions that affect pregnancy outcome. PMID- 20572621 TI - Benjamin's waterbirth. PMID- 20572622 TI - An afternoon with Marsden. PMID- 20572623 TI - Learning to listen. PMID- 20572624 TI - Reclaiming every woman's birth right. PMID- 20572625 TI - Facing fears, embracing birth. PMID- 20572626 TI - Breaking the law: midwives and civil disobedience. PMID- 20572627 TI - Brewer babies. PMID- 20572628 TI - Medical model still dominant in Spain. PMID- 20572629 TI - Diary of a midwife: Uganda. PMID- 20572630 TI - The new generation of Rincoeno. PMID- 20572631 TI - Brazilian love rebels: bringing awareness and consciousness to a birth-broken nation. PMID- 20572632 TI - One trip around the sun. PMID- 20572633 TI - Shasti Ma. PMID- 20572634 TI - Identification of tyrosine-phosphorylated proteins associated with lung cancer metastasis using label-free quantitative analyses. AB - Lung cancer is a lethal disease, and early metastasis is the major cause of treatment failure and cancer-related death. Tyrosine phosphorylated (P-Tyr) proteins are involved in the invasive and metastatic behavior of lung cancer; however, only a limited number of targets were identified. We attempt to characterize P-Tyr proteins and events involved in the metastatic process. In a previous work, we have developed a strategy for identification of protein phosphorylation. Here, this strategy was used to characterize the tyrosine phosphoproteome of lung cancer cells that have different invasive abilities (CL1 0 vs. CL1-5). Using our analytical strategy, we report the identification of 335 P-Tyr sites from 276 phosphoproteins. Label-free quantitative analysis revealed that 36 P-Tyr peptides showed altered levels between CL1-0 and CL1-5 cells. From this list of sites, we extracted two novel consensus sequences and four known motifs for specific kinases and phosphatases including EGFR, Src, JAK2, and TC PTP. Protein-protein interaction network analysis of the altered P-Tyr proteins illustrated that 11 proteins were linked to a network containing EGFR, c-Src, c Myc, and STAT, which is known to be related to lung cancer metastasis. Among these 11 proteins, 7 P-Tyr proteins have not been previously reported to be associated with lung cancer metastasis and are of greatest interest for further study. The characterized tyrosine phosphoproteome and altered P-Tyr targets may provide a better comprehensive understanding of the mechanisms of lung cancer invasion/metastasis and discover potential therapies. PMID- 20572636 TI - Simple interpretative model for the anomalous behavior of the excess surface area in mixed systems with large composition fluctuations: a theoretical analysis and an experimental investigation of mixed phospholipid/omega-3 fatty acid Langmuir Blodgett films. AB - We derive an elementary phenomenological lattice hole model to describe the complex behavior of the excess surface area as a function of the composition in two-component monolayers. The model accounts for the coupling between the composition fluctuations and the density (holes) concentration in mixed films. When the composition fluctuations are large and the hole-composition coupling parameters are strong, our model predicts the occurrence of a double maximum (or minimum) in the plot of the excess surface area A(E) against the film composition. The theoretical results are compared with excess surface area measurements of Langmuir-Blodgett films of mixed phospholipid/omega-3 fatty acids performed at different temperature, pH, and pressure. PMID- 20572635 TI - Trust, but verify: on the importance of chemical structure curation in cheminformatics and QSAR modeling research. PMID- 20572637 TI - Comparative NMR properties of H2 and HD in toluene-d8 and in H2/HD@C60. AB - Spin-lattice relaxation times, T(1), have been measured from 200-340 K for the protons in H(2) and HD molecules dissolved in toluene-d(8) and incarcerated in C(60). It is found that HD relaxes more slowly than H(2) in both environments and at all temperatures, as expected from the smaller values of the spin-rotation and dipole-dipole coupling in HD compared to H(2). More detailed analysis using models developed to describe relaxation in both condensed media and the gas phase indicates that transitions among the rotational states of H(2) occur at a rate similar to those of HD in both toluene-d(8) solution and in C(60), in contrast to the situation in gas phase collisions between hydrogen and He or Ar, where the lifetimes of rotational states of HD are markedly shorter than those for H(2). Measurements of the relative (1)H chemical shifts of H(2) and HD, the coupling constant J(HD), and the widths of the HD peaks at various temperatures revealed only small effects with insufficient accuracy to warrant more detailed interpretation. PMID- 20572638 TI - Supported lipid bilayers on mica and silicon oxide: comparison of the main phase transition behavior. AB - The usual biophysical approach to the study of biological membranes is that of turning to model systems. From these models, general physical principles ruling the lateral membrane structure can be obtained. A promising model system is the supported lipid bilayer (SLB) which could foresee the simultaneous investigation of the structure and physical properties of lipid bilayers reconstituted with membrane proteins. A complete exploitation of the model system to retrieve biologically relevant information requires an in-depth knowledge of the possible effect that experimental parameters could have on the behavior of the SLB. Here we used atomic force microscopy (AFM) to study the effect of different types of substrates on the behavior of SLBs as far as their main phase transition is concerned. We found that different substrates (mica and silicon oxide) can affect in dissimilar ways the interleaflet coupling of the bilayer, which might represent a sort of lipid signaling allowing communication between receptors on the extracellular leaflet and cytoplasmic components. By decreasing the interaction between the SLB and the substrate the interleaflet coupling is preserved independently of the bilayer preparation strategy. Moreover, we investigated by time-lapse AFM an isothermal phase transition induced by a pH change on a SLB. We established that the presence of a pH gradient across the bilayer can weaken the strength of the interleaflet coupling which is present in symmetrical pH conditions. PMID- 20572639 TI - Modeling localized photoinduced electrons in rutile-TiO2 using periodic DFT+U methodology. AB - We propose a theoretical model for photocatalytic processes on titanium dioxide, described by its most stable phase and surface, rutile-TiO(2)(110). The excitation induced by light promotes electrons from the valence band to the conduction band. In this context, one important requirement is having a correct value of the magnitude of the electronic gap. The use of GGA+U or LDA+U functional with an appropriate U value allows this. The U correction has little consequence on the adsorption strength itself on the TiO(2)(110) surface. For the ground state, it only yields a slight increase of the interaction strength of some test molecules; the surface basicity is somewhat enhanced. This is interpreted by the shift of TiO(2) vacant levels. Photoexcitation is taken into account by imposing two unpaired electrons per cell of the same spin. The size of the cell therefore determines the number of excitations per surface area; the larger the cell, the smaller the electron-hole surface concentration and the smaller the energy for electronic excitation. For the excited state, careful attention must be focused on the localization of the excited electron and of the hole which are crucial for the determination of the lowest electronic states and for the surface reactivity. We found that the excited electron is localized on a pentacoordinated surface titanium atom while the hole is shared by two surface oxygen atoms not too far from it. The electronic levels associated to the reduced titanium atoms are low in energy; the projected density of states is superposed onto the valence band. PMID- 20572640 TI - Novel nanocomposites made of boron nitride nanotubes and a physical gel. AB - This article describes successful incorporation of multiwalled boron nitride nanotubes (BNNTs) and various functionalized BNNTs by Lewis bases such as trioctylamine (TOA), tributylamine (TBA), and triphenylphosphine (TPP), etc., in organogels formed by triphenylenevinylene (TPV)-based low molecular weight gelator (LMWG) in toluene and consequent characterization of the resulting gel nanocomposites. Functionalized BNNTs were synthesized first, and the presence of tubular structures with high aspect ratio and increased diameter compared to the starting BNNTs was confirmed by SEM, TEM, and Raman spectroscopy. The micrographs of composites of 1 and BNNTs showed evidence of wrapping of the gelator molecules on to the BNNT surface presumably brought about by pi-pi stacking and van der Waals interactions. This leads to the formation of densely packed and directionally aligned fibrous networks. Such "reinforced" aggregation of the gelator molecules in presence of doped BNNTs led to an increase in the sol-to-gel transition temperature and the solidification temperature of the gel nanocomposites as revealed from differential scanning calorimetry. Rheological investigations of the gel nanocomposites indicate that the flow properties of the resulting materials become resistant to applied stress upon incorporation of even a very low wt % of BNNTs. Finally, the increase in thermal conductivity of the nanocomposite compared to the gelator alone was observed for the temperature range of 0-60 degrees C which may make these composites potentially useful in various applications depending on the choice and the amount of BNNT loading in the composite. PMID- 20572641 TI - Computational studies of the thermochemistry for conversion of glucose to levulinic acid. AB - The thermochemistry of the conversion of glucose to levulinic acid through fructofuranosyl intermediates is investigated using the high-level ab initio methods G4 and G4MP2. The calculated gas phase reaction enthalpies indicate that the first two steps involving water molecule elimination are highly endothermic, while the other steps, including additional water elimination and rehydration to form levulinic acid, are exothermic. The calculated gas phase free energies indicate that inclusion of entropic effects makes the dehydration steps more favorable, although the elimination of the first water is still endothermic. Elevated temperatures and aqueous reaction environments are also predicted to make the dehydration reaction steps thermodynamically more favorable. On the basis of these enthalpy and free energy calculations, the first dehydration step in conversion of glucose to levulinic acid is likely a key step in controlling the overall progress of the reaction. An assessment of density functional theories and other theoretical methods for the calculation of the dehydration and hydration reactions in the decomposition of glucose is also presented. PMID- 20572642 TI - Self-introduction of disordered lattice distortion by a polymeric nanofiber laser. AB - The developed molecular dynamics shows that upon photoexcitation of a conjugated polymer nanofiber, such as poly(phenylene vinylene)s or the polyfluorene family, singlet excitons initially are formed. Through continuous optical pumping, the electron populations of the excitons are reversed. Different from inorganic materials, the electron population reversion not only generates new localized electron states but also destroys the periodic structure of the polymer chain, inducing localized lattice distortion. These localized modes provide one of the channels to form localized lasing emission in a single conjugated nanofiber laser, which is consistent with recent experimental observations. PMID- 20572643 TI - Highly fluorescent aggregates modulated by surfactant structure and concentration. AB - The effects of anionic surfactants on the aggregation-induced emission (AIE) feature of cationic M-silole molecules have been studied. The electrostatic binding of M-silole with the surfactants greatly promotes the aggregation of the mixtures. The M-silole/surfactant aggregates at 1:1 charge ratio exhibit the maximum fluorescence intensity. Excess surfactant molecules will distribute the M silole molecules into different micelles and weaken the fluorescence. The fluorescence intensity of the mixed M-silole/surfactant aggregates can be effectively modulated by choosing different surfactants. The gemini surfactants display a much stronger ability of enhancing fluorescence intensity than do the single-chain surfactants. Especially, the gemini surfactant with benzene rings shows the best performance in enhancing fluorescence of M-silole due to both the strongest aggregation ability and the pi-pi interaction with M-silole. PMID- 20572644 TI - Formation of stable BOBO-3 H-aggregate complexes hinders DNA hybridization. AB - In recent works, we have been studying the photophysics and binding properties of the trimethine cyanine homodimer dye BOBO-3, a DNA intercalative fluorophore that shows an important fluorescence enhancement upon binding to double-stranded DNA. During the course of studying the interactions of the dye with single-stranded homo-oligonucleotides we detected the apparition of an additional absorption band centered on 466 nm. The large hypsochromic effect and the fact that direct excitation of this band resulted in negligible fluorescence emission are characteristic properties of an H-type molecular aggregate. In this work we study the properties of this H-aggregate, and obtain by means of Principal Component Analysis the spectral shape and association constant of the complex. The H aggregate complex shows very unique features. On one hand, the nucleotide bases cytosine or adenine are crucially involved in the formation of the aggregate. We describe here that at least six consecutive cytidine nucleosides are required to properly form the BOBO-3 H-aggregate complex. On the other hand, we demonstrate that the formation of such a stable complex prevents hybridization of the bases involved with their complementary strands. This phenomenon draws important conclusions on the anomalously high stability of the BOBO-3 H-aggregate complex. To the best of our knowledge, this is the first time such a stable H-aggregate of a dimeric cyanine dye facilitated by specific nucleotide bases in single strands has been reported. PMID- 20572645 TI - Effect of divalent cationic ions on the adsorption behavior of zwitterionic surfactant at silica/solution interface. AB - The adsorption behavior of zwitterionic surfactant dodecyl sulfobetaine (DBS) on a silica/solution interface with Ca(2+), Mg(2+) existing in aqueous solution is explored by atomistic molecular simulations. The interaction energy contribution of van der Waals and electrostatic potentials in the surfactants/water/silica system are respectively calculated, from which the electrical interaction can be found to play a decisive role in the adsorption tendency of DBS on the silica surface with or without inorganic ions, despite different mechanisms. The distinct decrease of energy has been found to be derived from electrical interaction when DBS adsorb on the silica surface covered by Ca(2+) or Mg(2+). Therefore, it can be predicted that the cationic ions combined on the negatively charged silica surface in a mineral water medium might decrease the adsorption trend of DBS on the silica surface, which has been experimentally proven by TOC measurement. Structural information of the close interface layer and the distribution of water molecules are analyzed after the complete molecular dynamics simulation using a ternary model. Ca(2+) and Mg(2+) combined on the silica surface can reduce the adsorption amount of DBS by preventing the direct interaction between DBS and surface, and bringing about the orientation reversal of DBS molecules to break the order of adsorption interface layer. Furthermore, changes in the status of the water spreading on the silica surface caused by the complexation of cations are also an important reason in the adsorption reduction. PMID- 20572646 TI - Photopolymerization and formation of a stable purple Langmuir-Blodgett film based on the gemini-type amphiphilic diacetylene derivatives. AB - In this paper, we designed two gemini-type amphiphiles containing diacetylene units which were covalently linked through L-lysine or L-lysine ethyl ester moiety (abbreviated as TCDA-LysAc or TCDA-LysEs) as the spacer. These amphiphiles can be easily fabricated into organized molecular films though the Langmuir Blodgett technique and the films showed an excellent photopolymerization ability. Upon photopolymerization, TCDA-LysEs formed a purple LB film with an excellent stability, while TCDA-LysAc formed the film with mixed blue, purple, and red phases. Aligned nanofibers were observed for the TCDA-LysEs film, while a mixed domain with short fiber and rotted wood structure was obtained for TCDA-LysAc. Different supramolecular chirality was obtained for the transferred LB films although both the compounds have spacers with similar chirality. It was suggested that the subtle change in the spacer structure led to different noncovalent interactions, which subsequently affected the polymerization. Through such a molecular design, we have successfully obtained the stable purple poly(diacetylene) film. PMID- 20572648 TI - Dynamic NMR study of the kinetics of complexation of Tl(+) ion with calix[4]crown 6. AB - The complexation and exchange kinetics and mechanism for the dissociation and conformational change of thallium ion complex of calix[4]crown-6 were studied in CD(3)CN/CDCl(3) (4:1 v/v) solution by dynamic (1)H NMR. The results show the formation of a 1:1 complex with cone conformation. From variable temperature dynamic NMR analysis in the range 223-293 K, two coalescence temperatures at 228 and 243 K were ascertained. The activation parameters for the dissociation process, E(a) (kJ/mol), DeltaS(++) (J/mol.K), and DeltaH(++) (kJ/mol) are 11.0, 133.2, and 10.1 for the bimolecular regime and 21.5, -112.8, and 20.6 for the unimolecular regime, respectively. In addition, the dynamic (1)H NMR spectroscopy shows that the exchange of Tl(+) between the two crown sides of the complexed ligand proceeds through an intramolecular tunneling. An Arrhenius convex curve was observed for intramolecular exchange. This phenomenon is explained in terms of two conformer state formations differentiated by hydrogen bond association. PMID- 20572649 TI - The wormlike micellar solution made of a zwitterionic surfactant (TDPS), an anionic surfactant (SDS), and brine in the semidilute regime. AB - Structural and dynamical properties of a micellar solution are studied mainly through examining its rheological behavior in the semidilute regime. The micellar solution is made of a zwitterionic surfactant N-tetradecyl-N,N-dimethyl-3-ammonio 1-propanesulfonate, sodium dodecyl sulfate, and salty water. In particular, we are interested in how the system is affected when the ionic strength of the media is modified by adding salt. Until recently, it was known that this solution forms wormlike micelles. In a range of chemical composition, the solution behaves as a viscoelastic Maxwellian fluid at low frequencies. We present measurements of the elastic (storage) modulus and the viscous (loss) modulus varying the surfactant ratio (R = [SDS]/[TDPS]), and how the Maxwellian relaxation time abruptly increases when the NaCl concentration is also varied. Reptation and breaking/recombination times were estimated. The effect of temperature in the viscoelastic solution is also studied. Shear stress versus shear rate flow curves were measured under shear and stress control, for different micellar solutions with different composition, brine concentration, and temperature, showing a nonlinear behavior. Flow curves present two branches, one corresponding to high viscous fluid and another to low viscous fluid, separated by a stress plateau. We were able to develop a master dynamic phase diagram, which summarizes the nonlinear behavior by appropriately reducing the rheological variables. In the stress plateau, the micellar solution presents gradient shear banding, which was observed with the scattered light of a sheet of light perpendicular to the fluid flow velocity in the gap of a transparent Couette rheometer. PMID- 20572650 TI - Reduction of surface charges during coalescence of elastomer particles. AB - Reaction-limited aggregation of soft elastomer particles has been studied with specific attention to the fate of surface charges during coalescence. The employed system is an aqueous dispersion of fluoroelastomer particles, which are known to coalesce completely at 70 degrees C. In contrast to diffusion-limited conditions, under reaction-limited conditions the stability of the system is expected to change during aggregation because of surface reduction and charge accumulation resulting from coalescence. This allows investigating the mechanism of charge relocation during cluster coalescence. For particles stabilized by ionic surfactants, it has been found that the charges are mobile (i.e., they redistribute between aqueous solution and particle surface according to their adsorption equilibrium) (Gauer, C.; Jia, Z.; Wu, H.; Morbidelli, M. Langmuir 2009, 25, 9703). In this work, we consider the case of fixed charges, as those given by charged polymer end groups covalently bound to the particle surface. We demonstrate that a loss of fixed surface charges occurs during the coalescence and strongly affects the time evolution and the shape of the resulting cluster mass distribution. PMID- 20572647 TI - Fundamental reaction pathways for cytochrome P450-catalyzed 5'-hydroxylation and N-demethylation of nicotine. AB - The reaction pathways for 5'-hydroxylation and N-demethylation of nicotine catalyzed by cytochrome P450 were investigated by performing a series of first principle electronic structure calculations on a catalytic reaction model system. The computational results indicate that 5'-hydroxylation of nicotine occurs through a two-state stepwise process, that is, an initial hydrogen atom transfer from nicotine to Cpd I (i.e., the HAT step) followed by a recombination of the nicotine moiety with the iron-bound hydroxyl group (i.e., the rebound step) on both the high-spin (HS) quartet and low-spin (LS) doublet states. The HAT step is the rate-determining one. This finding represents the first case that exhibits genuine rebound transition state species on both the HS and the LS states for C(alpha)-H hydroxylation of amines. N-Demethylation of nicotine involves a N methylhydroxylation to form N-(hydroxymethyl)nornicotine, followed by N (hydroxymethyl)nornicotine decomposition to nornicotine and formaldehyde. The N methylhydroxylation step is similar to 5'-hydroxylation, namely, a rate determining HAT step followed by a rebound step. The decomposition process occurs on the deprotonated state of N-(hydroxymethyl)nornicotine assisted by a water molecule, and the energy barrier is significantly lower than that of the N methylhydroxylation process. Comparison of the rate-determining free energy barriers for the two reaction pathways predicts a preponderance of 5' hydroxylation over the N-demethylation by roughly a factor of 18:1, which is in excellent agreement with the factor of 19:1 derived from available experimental data. PMID- 20572651 TI - Intramolecular pi-type hydrogen bonding and conformations of 3-cyclopenten-1-ol. 2. Infrared and Raman spectral studies at high temperatures. AB - The vapor-phase infrared and Raman spectra of 3-cyclopenten-1-ol (3CPOL) have been collected at temperatures ranging from 25 to 267 degrees C. These clearly show the presence of four conformations of 3CPOL with the one with intramolecular pi-type hydrogen bonding being most abundant. The spectra of all four conformations have been assigned, and these agree well with the computed values from the DFT calculation. The frequency shifts observed for the different conformations are in accord with the predicted values. In the O-H stretching region the conformer A with the pi-type intramolecular hydrogen bond has the lowest stretching frequency at 3623.4 cm(-1) while the three higher energy conformers have frequencies 14.2, 32.0, and 36 cm(-1) higher. In the C=C stretching region conformer A again has the lowest frequency at 1607.3 cm(-1) while the other conformers have bands 2.1, 8.0, and 13.4 cm(-1) lower. Both the O H stretching and the C=C stretching force constants are decreased about 2% by the hydrogen bonding. Five of the other vibrations show significant predicted frequency shifts up to 193 cm(-1). Analysis of intensity data at different temperatures was used to calculate the energy difference between the two most stable conformers. This was found to be 435 +/- 160 cm(-1), and the result agrees reasonably well with the high level ab initio results which range from 274 to 401 cm(-1). PMID- 20572652 TI - Intramolecular pi-type hydrogen bonding and conformations of 3-cyclopenten-1-ol. 1. Theoretical calculations. AB - The 3-cyclopenten-1-ol (3CPOL) molecule possesses two large-amplitude, low frequency vibrations, namely, the ring-puckering and OH internal rotation, which can interconvert its four conformers into each other. Ab initio and density functional theory (DFT) calculations have been carried out to understand the energetics of these conformational changes. The lowest energy 3CPOL conformer possesses weak pi-type intramolecular hydrogen bonding between the hydroxyl hydrogen and the carbon-carbon double bond, and this lies 274 cm(-1) (0.78 kcal/mol) to 420 cm(-1) (1.20 kcal/mol) lower in energy than the other three conformations according to CCSD/6-311++G(d,p) computations. The two-dimensional potential energy surface for 3CPOL was computed as a function of the ring puckering and OH internal rotation coordinates with the MP2/6-31+G(d,p) model. PMID- 20572653 TI - Extraction of magnetic coupling parameters in 2-dimensional magnetic honeycomb layers. AB - Quantum chemical calculations have been performed to determine the magnetic coupling between transition metals in the anionic layers of bifunctional materials. These layers are characterized by a hexagonal grid of oxalato-bridged transition metal ions, [M(2)(ox)(3)](2-), with M = Cu(2+), Ni(2+), Co(2+), Fe(2+). No experimental information is available for the coupling constants in these lattices. The magnetic coupling parameters are calculated through an embedded cluster containing two metal ions and the oxalato ligands coordinated to these. The calculated parameters are used to construct a larger model for which the temperature dependence of the magnetic susceptibility is calculated. The curves obtained compare reasonably well with experimental curves, validating the theoretical estimates of the magnetic coupling between the transition metals in the hexagonal lattices. PMID- 20572654 TI - Polymers at the water/air interface, surface pressure isotherms, and molecularly detailed modeling. AB - Surface pressure isotherms at the air/water interface are reproduced for four different polymers, poly-L-lactic acid (PLLA), poly(dimethylsiloxane) (PDMS), poly(methyl methacrylate) (PMMA), and poly(isobutylene) (PiB). The polymers have the common property that they do not dissolve in water. The four isotherms differ strongly. To unravel the underlying details that are causing these differences, we have performed molecularly detailed self-consistent field (SCF) modeling. We describe the polymers on a united atom level, taking the side groups on the monomer level into account. In line with experiments, we find that PiB spreads in a monolayer which smoothly thickens already at a very low surface pressure. PMMA has an autophobic behavior: a PMMA liquid does not spread on top of the monolayer of PMMA at the air/water interface. A thicker PMMA layer only forms after the collapse of the film at a relatively high pressure. The isotherm of PDMS has regions with extreme compressibility which are linked to a layering transition. PLLA wets the water surface and spreads homogeneously at larger areas per monomer. The classical SCF approach features only short-range nearest-neighbor interactions. For the correct positioning of the layering and for the thickening of the polymer films, we account for a power-law van der Waals contribution in the model. Two-gradient SCF computations are performed to model the interface between two coexistent PDMS films at the layering transition, and an estimation of the length of their interfacial contact is obtained, together with the associated line tension value. PMID- 20572655 TI - Guggenheim's rule and the enthalpy of vaporization of simple and polar fluids, molten salts, and room temperature ionic liquids. AB - One of Guggenheim's many corresponding-states rules for simple fluids implies that the molar enthalpy of vaporization (determined at the temperature at which the pressure reaches 1/50th of its critical value, which approximately coincides with the normal boiling point) divided by the critical temperature has a value of roughly 5.2R, where R is the universal gas constant. For more complex fluids, such as strongly polar and ionic fluids, one must expect deviations from Guggenheim's rule. Such a deviation has far-reaching consequences for other empirical rules related to the vaporization of fluids, namely Guldberg's rule and Trouton's rule. We evaluate these characteristic quantities for simple fluids, polar fluids, hydrogen-bonding fluids, simple inorganic molten salts, and room temperature ionic liquids (RTILs). For the ionic fluids, the critical parameters are not accessible to direct experimental observation; therefore, suitable extrapolation schemes have to be applied. For the RTILs [1-n-alkyl-3 methylimidazolium bis(trifluoromethylsulfonyl)imides, where the alkyl chain is ethyl, butyl, hexyl, or octyl], the critical temperature is estimated by extrapolating the surface tension to zero using Guggenheim's and Eotvos' rules; the critical density is obtained using the linear-diameter rule. It is shown that the RTILs adhere to Guggenheim's master curve for the reduced surface tension of simple and moderately polar fluids, but that they deviate significantly from his rule for the reduced enthalpy of vaporization of simple fluids. Consequences for evaluating the Trouton constant of RTILs, the value of which has been discussed controversially in the literature, are indicated. PMID- 20572656 TI - Theoretical investigations of geometry, electronic structure and stability of UO(6): octahedral uranium hexoxide and its isomers. AB - The existence of a novel octahedral UO(6) complex had been suggested by Pyykko et al. [Pyykko, P.; Runeberg, N.; Straka, M.; Dyall, K. G. Chem. Phys. Lett. 2000, 328, 415]. We have now investigated the stability, the geometric and electronic structures, and the vibrations of various UO(6) molecules, using spin-orbit density functional and scalar-relativistic coupled-cluster approaches. We find four different (meta-)stable species, namely (3)D(2h)-UO(2)(eta(2)-O(2)(*))(2) at lowest energy, (3)C(2v)-UO(4)(*)(eta(2)-O(2)(*)) and (1)D(3)-U(eta(2)-O(2))(3) at medium energies, and (1)O(h)-UO(6) at highest energy. The decay of O(h)-UO(6) occurs via an activated spin-flip mechanism. The UO(6) species correspond to local minima on singlet and triplet energy surfaces and might be trapped in noble gas matrices. Experimentally, the four species might be identified through their vibrational spectra. Uranium is best described as coordinated by oxygen atoms in various oxidation states as oxo O(2-), oxido(1) O(*-), peroxido O(2)(2-), and superoxido O(2)(*-) ligands. The occurrence of monovalent oxygen is remarkable. The resulting characterization of the central ion as U(VI) in all four cases does not fully reflect the electronic differences, nor the "valence-activity" of the U 6p(6) semicore shell. PMID- 20572657 TI - Structure and conformational stability of protonated dialanine. AB - A systematic investigation on the structure and stability of the four conformers of the protonated dialanine cation (transA1, transA2, transO1, cisA3) was performed employing the HF, MP2, and hybrid DFT methods with various basis sets which ranged from the 6-31G* to the basis set larger than the correlation consistent aug-cc-pVTZ basis set. It is found that the backbone dihedral angles and energies of the conformers are sensitive to the electron correlation level and basis set, especially manifesting slow convergence of conformer structure and energetics with basis set at the MP2 level. At the MP2 basis set limit corrected by CCSD(T) correlation effect, the lowest transA1 conformer is almost isoenergetic with the cisA3 conformer, followed by the transA2 conformer ( approximately 0.5 kcal/mol above transA1), and, last, the transO1 conformer ( approximately 1.2 kcal/mol above transA1). Vibrational and thermal (entropic) factors appear to have an important effect on the relative stability between conformers at room temperature, reducing the energy difference between transA1 and transA2 conformers and making cisA3 higher in energy than transA1 or transA2, which is in accord with the recent infrared multiphoton dissociation experimental data on this cation. According to the polarizable continuum model calculations, solvation of protonated dialanine in water would significantly enhance the stability of the transA2 conformer, making it most populated in aqueous solution at room temperature. Among the tested hybrid DFT methods in this study, B3LYP/6 31G* was found to be the most effective for predicting the conformational structures and relevant stability of protonated dialanine cation in the gas phase. PMID- 20572658 TI - Direct synthesis of polymer nanocapsules: self-assembly of polymer hollow spheres through irreversible covalent bond formation. AB - A detailed study of the direct synthesis of polymer nanocapsules, which does not require any template, and core removal, is presented. Thiol-ene "click" reaction between a CB[6] derivative (1) with 12 allyloxy groups at the periphery and dithiols directly produced polymer nanocapsules with a highly stable structure and relatively narrow size distribution. Based on a number of observations including the intermediates detected by DLS, TEM, and SEM studies, a mechanism of the nanocapsule formation was proposed, which includes 2D oligomeric patches turning into a hollow sphere. A theoretical study supports that the formation of a hollow sphere from a disk-shaped intermediate can be thermodynamically favorable under certain conditions. In particular, the effects of various factors such as monomer concentration, reaction temperature, and medium on the formation of polymer nanocapsules have been investigated, which qualitatively agree with those predicted by our theoretical model. An interesting feature of the polymer nanocapsules was that the polymer shell made of a CB[6] derivative allows facile tailoring of its surface properties in a noncovalent and modular manner by virtue of the unique recognition properties of the accessible molecular cavities exposed on the surface. Furthermore, this approach appears to be applicable to any building unit with a flat core and multiple polymerizable groups at the periphery which can direct polymer growth in lateral directions. Other reactions, such as amide bond formation, can be used for the synthesis of polymer nanocapsules in this approach. This novel approach to polymer nanocapsules represents a rare example of self-assembly of molecular components into nanometer-scale objects with interesting structures, shapes, and morphology through irreversible covalent bond formation. PMID- 20572659 TI - Morphology control of nanostructures via surface reaction of metal nanodroplets. AB - We report on the controllable synthesis of diverse nanostructures using laser ablation of a metal target in a liquid medium. The nanodroplets generated by laser ablation react with the liquid and produce various nanostructures, such as hollow nanoparticles, core-shell nanoparticles, heterostructures, nanocubes, and ordered arrays. A millisecond laser with low power density is essential for obtaining such metal nanodroplets, while the target material, the reactivity of liquid medium, and the laser frequency are decisive for controlling the morphology and size of the nanostructures produced. This green and powerful technique can be extended to different material systems for obtaining various nanostructures. PMID- 20572660 TI - Nature of the energy landscape for gated electron transfer in a dynamic redox protein. AB - Conformational control limits most electron transfer (ET) reactions in biology, but we lack general insight into the extent of conformational space explored, and specifically the properties of the associated energy landscape. Here we unite electron-electron double resonance (ELDOR) studies of the diradical (disemiquinoid) form of human cytochrome P450 reductase (CPR), a nicotinamide adenine phosphate dinucleotide (NADPH)-linked diflavin oxidoreductase required for P450 enzyme reduction, with functional studies of internal ET to gain new insight into the extent and properties of the energy landscape for conformationally controlled ET. We have identified multiple conformations of disemiquinoid CPR, which point to a rugged energy landscape for conformational sampling consistent with functional analysis of ET using high-pressure stopped flow, solvent, and temperature perturbation studies. Crystal structures of CPR have identified discrete "closed" and "open" states, but we emphasize the importance of a continuum of conformational states across the energy landscape. Within the landscape more closed states that favor internal ET are formed by nucleotide binding. Open states that enable P450 enzymes to gain access to electrons located in the FMN-domain are favored in the absence of bound coenzyme. The extent and nature of energy landscapes are therefore accessible through the integration of ELDOR spectroscopy with functional studies. We suggest this is a general approach that can be used to gain new insight into energy landscapes for biological ET mediated by conformational sampling mechanisms. PMID- 20572661 TI - Dynamic kinetic asymmetric synthesis of substituted pyrrolidines from racemic cyclopropanes and aldimines: reaction development and mechanistic insights. AB - An enantioselective preparation of 2,5-cis-disubstituted pyrrolidines has been achieved via a dynamic kinetic asymmetric transformation (DyKAT) of racemic donor acceptor cyclopropanes and (E)-aldimines. Mechanistic studies suggest that isomerization of the aldimine or resultant iminium to the Z geometry is not a pathway that furnishes the observed 2,5-cis-disubstituted products. PMID- 20572662 TI - Time-dependent polymerization kinetic study and the properties of hybrid polymers with functional silsesquioxanes. AB - Methacrylate-functionalized cubic silsesquioxane homopolymers [p(MA-CSSQ)] were synthesized by reversible addition-fragmentation chain transfer (RAFT)-mediated living radical polymerization in the presence of dodecyl(dimethylacetic acid)trithiocarbonate (DDTA) chain transfer agent, and their polymerization kinetics were studied. The DDTA-terminated p(MA-CSSQ) was then employed as a macro-RAFT agent in the polymerization of methylmethacrylate (MMA) for the synthesis of a brushlike p(MA-CSSQ)-b-PMMA block copolymer. The kinetics study of p(MA-CSSQ) showed that the monomer to polymer conversion, evaluated by (1)H NMR, was found to be approximately 80% with the maximum number average molecular weight (M(n)) of 24000 and 32300 Da, for the [MA-CSSQ]/[DDTA] ratios of 100 and 200, respectively, as determined by gel permeation chromatography (GPC). The broadening of molecular weight distributions in p(MA-CSSQ) homopolymer GPC traces was observed, presumably due to the presence of the radical-radical termination products. The resultant homopolymer and block copolymer exhibited excellent thermal stability as evidenced by thermogravimetric and differential scanning calorimetric analyses. The surface properties of p(MA-CSSQ) homopolymer and p(MA CSSQ)-b-PMMA block copolymer, determined by water contact angle and atomic force microscopy (AFM) measurements, strongly indicated the surface enrichment of the hydrophobic silsesquioxane groups. The AFM images showed the microsized granular domains of p(MA-CSSQ) homopolymer, whereas the islandlike phase-separated domains were observed in p(MA-CSSQ)-b-PMMA block copolymer. PMID- 20572663 TI - Molecular mechanisms in morpholino-DNA surface hybridization. AB - Synthetic nucleic acid mimics provide opportunity for redesigning the specificity and affinity of hybridization with natural DNA or RNA. Such redesign is of great interest for diagnostic applications where it can enhance the desired signal against a background of competing interactions. This report compares hybridization of DNA analyte strands with morpholinos (MOs), which are uncharged nucleic acid mimics, to the corresponding DNA-DNA case in solution and on surfaces. In solution, MO-DNA hybridization is found to be independent of counterion concentration, in contrast to DNA-DNA hybridization. On surfaces, when immobilized MO or DNA "probe" strands hybridize with complementary DNA "targets" from solution, both the MO-DNA and DNA-DNA processes depend on ionic strength but exhibit qualitatively different behaviors. At lower ionic strengths, MO-DNA surface hybridization exhibits hallmarks of kinetic limitations when separation between hybridized probe sites becomes comparable to target dimensions, whereas extents of DNA-DNA surface hybridization are instead consistent with limits imposed by buildup of surface (Donnan) potential. The two processes also fundamentally differ at high ionic strength, under conditions when electrostatic effects are weak. Here, variations in probe coverage have a much diminished impact on MO-DNA than on DNA-DNA hybridization for similarly crowded surface conditions. These various observations agree with a structural model of MO monolayers in which MO-DNA duplexes segregate to the buffer interface while unhybridized probes localize near the solid support. A general perspective is presented on using uncharged DNA analogues, which also include compounds such as peptide nucleic acids (PNA), in surface hybridization applications. PMID- 20572665 TI - Magnetic conjugated polymer nanoparticles as bimodal imaging agents. AB - Hybrid nanoparticles which incorporate multiple functionalities, such as fluorescence and magnetism, can exhibit enhanced efficiency and versatility by performing several tasks in parallel. In this study, magnetic-fluorescent semiconductor polymer nanospheres (MF-SPNs) have been synthesized by encapsulation of hydrophobic conjugated polymers and iron oxide nanoparticles in phospholipid micelles. Four fluorescent conjugated polymers were used, yielding aqueous dispersions of nanoparticles which emit across the visible spectrum. The MF-SPNs were shown to be magnetically responsive and simultaneously fluorescent. In MRI studies, they were seen to have a shortening effect on the transverse T(2)* relaxation time, which demonstrates their potential as an MR contrast agent. Finally, successful uptake of the MF-SPNs by SH-SY5Y neuroblastoma cells was demonstrated, and they were seen to behave as bright and stable fluorescent markers. There was no evidence of toxicity or adverse affect on cell growth. PMID- 20572664 TI - NMR and DFT investigation of heme ruffling: functional implications for cytochrome c. AB - Out-of-plane (OOP) deformations of the heme cofactor are found in numerous heme containing proteins and the type of deformation tends to be conserved within functionally related classes of heme proteins. We demonstrate correlations between the heme ruffling OOP deformation and the (13)C and (1)H nuclear magnetic resonance (NMR) hyperfine shifts of heme aided by density functional theory (DFT) calculations. The degree of ruffling in the heme cofactor of Hydrogenobacter thermophilus cytochrome c(552) has been modified by a single amino acid mutation in the second coordination sphere of the cofactor. The (13)C and (1)H resonances of the cofactor have been assigned using one- and two-dimensional NMR spectroscopy aided by selective (13)C-enrichment of the heme. DFT has been used to predict the NMR hyperfine shifts and electron paramagnetic resonance (EPR) g tensor at several points along the ruffling deformation coordinate. The DFT predicted NMR and EPR parameters agree with the experimental observations, confirming that an accurate theoretical model of the electronic structure and its response to ruffling has been established. As the degree of ruffling increases, the heme methyl (1)H resonances move upfield while the heme methyl and meso (13)C resonances move downfield. These changes are a consequence of altered overlap of the Fe 3d and porphyrin pi orbitals, which destabilizes all three occupied Fe 3d based molecular orbitals and decreases the positive and negative spin density on the beta-pyrrole and meso carbons, respectively. Consequently, the heme ruffling deformation decreases the electronic coupling of the cofactor with external redox partners and lowers the reduction potential of heme. PMID- 20572667 TI - In vitro and in vivo studies of FePt nanoparticles for dual modal CT/MRI molecular imaging. AB - The water-solvable FePt nanoparticles of 3, 6, and 12 nm in diameter (3 nm-, 6 nm , and 12 nm-FePt) were synthesized and applied as a dual modality contrast agent for CT/MRI molecular imaging. These nanoparticles present excellent biocompatibility and hemocompatibility in all test concentrations for the imaging contrast. The biodistribution analysis revealed the highest serum concentration and circulation half-life for 12 nm-FePt, followed by 6 nm-FePt then 3 nm-FePt. Thus, the 3 nm-FePt showed higher brain concentrations. Anti-Her2 antibody conjugated FePt nanoparticles demonstrated molecular expression dependent CT/MRI dual imaging contrast effect in MBT2 cell line and its Her2/neu gene knock out counterpart. Selective contrast enhancement of Her2/neu overexpression cancer lesions in both CT and MRI was found in tumor bearing animal after tail vein injection of the nanoparticles. The 12 nm-FePt outperformed 3 nm-FePt in both imaging modalities. These results indicate the potential of FePt nanoparticles to serve as novel multimodal molecular imaging contrast agents in clinical settings. PMID- 20572666 TI - Structural, NMR spectroscopic, and computational investigation of hemin loading in the hemophore HasAp from Pseudomonas aeruginosa. AB - When challenged by low-iron conditions several Gram-negative pathogens secrete a hemophore (HasA) to scavenge hemin from its host and deliver it to a receptor (HasR) on their outer membrane for internalization. Here we report results from studies aimed at probing the structural and dynamic processes at play in the loading of the apo-hemophore secreted by P. aeruginosa (apo-HasAp) with hemin. The structure of apo-HasAp shows a large conformational change in the loop harboring axial ligand His32 relative to the structure of holo-HasAp, whereas the loop bearing the other axial ligand, Tyr75, remains intact. To investigate the role played by the axial ligand-bearing loops in the process of hemin capture we investigated the H32A mutant, which was found to exist as a monomer in its apo form and as a mixture of monomers and dimers in its holo-form. We obtained an X ray structure of dimeric H32A holo-HasAp, which revealed that the two subunits are linked by cofacial interactions of two hemin molecules and that the conformation of the Ala32 loop in the dimer is identical to that exhibited by the His32 loop in wild type apo-HasAp. Additional data suggest that the conformation of the Ala32 loop in the dimer is mainly a consequence of dimerization. Hence, to investigate the effect of hemin loading on the topology of the His32 loop we also obtained the crystal structure of monomeric H32A holo-HasAp coordinated by imidazole (H32A-imidazole) and investigated the monomeric H32A HasAp and H32A imidazole species in solution by NMR spectroscopy. The structure of H32A imidazole revealed that the Ala32 loop attains a "closed" conformation nearly identical to that observed in wild type holo-HasAp, and the NMR investigations indicated that this conformation is maintained in solution. The NMR studies also highlighted conformational heterogeneity at the H32 loop hinges and in other key sections of the structure. Targeted molecular dynamics simulations allowed us to propose a possible path for the closing of the His32 loop upon hemin binding and identified molecular motions that are likely important in transmitting the presence of hemin in the Tyr75 loop to the His32 loop to initiate its closing. Importantly, residues implicated as undergoing motions in the computations are also observed as being dynamic by NMR. Taken together, these observations provide direct experimental evidence indicating that hemin loads onto the Tyr75 loop of apo-HasAp, which triggers the closing of the His32 loop. PMID- 20572668 TI - Diazaphospholenes: N-heterocyclic phosphines between molecules and Lewis pairs. AB - The interest in geometrically distorted or electronically polarized molecules is often motivated by the realization that unusual structures can engender unprecedented physical or chemical properties. 1,3,2-Diazaphospholenes are N heterocyclic phosphines (NHPs) that have ring structures similar to N heterocyclic carbenes (NHCs). Although NHPs were initially mainly of interest as precursors for carbene-analogous phosphenium cations, it was noted that they exhibit quite peculiar structural features and remarkable chemical behavior on their own. In this Account, we discuss both structure and chemistry in connection with the special bonding situation that is characterized by significant n(N) sigma*(P-X) hyperconjugation and induces a strong ionic polarization of the P-X bonds. This induced polarization is surprisingly maintained even when P and X have similar or like electronegativities (for example, X = H, P) and offers the possibility to design compounds with polarized homonuclear bonds. An exemption from the general pattern was only noted for some P-amino-NHPs in which reverse hyperconjugation weakens endocyclic P-N bonds and was predicted to facilitate ring fragmentation and formation of phosphinidenes. An important corollary of the P-X bond polarization in NHPs is a unique bond lengthening, which not only can be fine-tuned by adjusting intramolecular steric and electronic interactions but also responds to intermolecular influences and solvent effects. Insight from crystallographic, spectroscopic, and computational studies allows the development of concepts for controlled manipulation of the bonding, up to a point where P-X bonds are dominated by electrostatic interactions and species behave as Lewis pairs rather than covalent molecules. An appealing aspect lies in the fact that this P-X bond polarization induces reactivities that have hardly any precedence in phosphine chemistry. Examples include (i) reactions of P-hydrogen-substituted NHPs as hydride transfer reagents, (ii) metatheses and additions to multiple bonds (diphosphination) of phosphino-NHPs, which can be used to catalyze P-C cross-coupling reactions and to synthesize 1,2-bisphosphine ligands, (iii) cyclopentadienyl (Cp) transfer reactions of P-Cp-NHPs, and (iv) metal insertion into the P-X bonds of P-halogeno-NHPs. In many aspects, these reactions have potentially useful mechanistic or synthetic implications, and their future exploitation might help to convert NHPs from academically interesting species into useful reagents. PMID- 20572669 TI - Investigation of reactive alpha-dicarbonyl compounds generated from the Maillard reactions of L-methionine with reducing sugars via their stable quinoxaline derivatives. AB - The formation of alpha-dicarbonyl compounds was investigated in methionine catalyzed (Maillard reaction) thermal degradation of d-glucose, maltose, and dextrin 10 at three different pH values (3, 5, and 8). The alpha-dicarbonyl compounds were trapped as quinoxalines and could be quantified by HPLC and GC-MS. Formation of 1,4-dideoxypentodiulose from hexoses and disaccharides was evidenced for the first time. The use of l-methionine as the amino compound for the formation of 1,4-dideoxypentodiulose in model systems is explained. Furthermore, it could be shown that methionine has great effect on the formation of specific alpha-dicarbonyl compounds. At various pH values and also by application of mono , di-, and oligosaccharides in all model reactions, 3-deoxyhexosulose and 1,4 dideoxypentodiulose were generated preferentially. PMID- 20572670 TI - Starch digestion mechanistic information from the time evolution of molecular size distributions. AB - Size-exclusion chromatography [SEC, also termed gel permeation chromatography (GPC)] is used to measure the time evolution of the distributions of molecular size and of branch length as starch is subjected to in vitro digestion, including studying the development of enzyme-resistant starch. The method is applied to maize starches with varying amylose contents; the starches were extruded so as to provide an analogue for processed food. The initial rates of digestion of amylose and amylopectin components were found to be the same for high-amylose starches. A small starch species, not present in the original starting material, was formed during the digestion process; this new species has a slower digestion rate and is probably formed by retrogradation of longer branches of amylose and amylopectin as they are partially or wholly liberated from their parent starch molecule during the digestion process. The data suggest that the well-known connection between high amylose content and resistant starch arises from the greater number of longer branches, which can form the small retrograded species. The method is useful for the purpose of comparisons between different starches undergoing the process of digestion, by observing the changes in their molecular structures, as an adjunct to detailed studies of the enzyme-resistant fraction. PMID- 20572671 TI - Antioxidant and anti-inflammatory activities of bean ( Phaseolus vulgaris L.) hulls. AB - Hulls obtained by mechanical abrasive dehulling from four bean cultivars were extracted with two solvents, aqueous (70%) acetone and water, and the extracts evaluated for antioxidant and anti-inflammatory activities in relation to their phenolic contents. Total phenolic content and antioxidant activity of bean hulls, measured using oxygen radical absorbance capacity (ORAC) values, were 6-8-fold those of corresponding whole beans. Aqueous acetone (70%) extracted over twice the amount of total phenolics from hulls that exhibited significantly higher antioxidant and stronger inhibitory effect on both cyclooxygenases, COX-1 and COX 2, than water. Acetone extract of black bean hull exhibited strong COX-1 (IC(50) = 1.2 microg/mL) and COX-2 (IC(50) = 38 microg/mL) inhibitory effects, even outperforming aspirin. Bean hull water extracts were stronger inhibitors of lipoxygenase, 15-LOX, than corresponding acetone extracts. Anti-inflammatory activity of bean hulls was dependent on their phenolic content and antioxidant activity that were significantly affected by cultivar and extracting solvent. PMID- 20572672 TI - One-flask syntheses of c-di-GMP and the [Rp,Rp] and [Rp,Sp] thiophosphate analogues. AB - An integrated set of reactions and conditions that allow an eight-step one-flask synthesis of the protected derivatives of c-di-GMP and the [R(p),R(p)] and [R(p),S(p)] thiophosphate analogues is reported. Deprotection is also carried out as a one-flask procedure, with the final products isolated by crystallization from the reaction mixture. Chromatography is only used for separation of the thiophosphate diastereomers. PMID- 20572673 TI - Evidence of hydrogen migration in an alkylphenyldiazirine excited state. AB - Ultrafast photolysis (350 nm) of alkylphenyldiazirines promotes the diazirine to the S(1) excited state. Solvent and substituent effects on the excited state lifetimes indicate that the S(1) state is highly polarized and undergoes a [1,2] H shift in concert with nitrogen extrusion in cyclohexane. PMID- 20572674 TI - Beta-cyclodextrin/surface plasmon resonance detection system for sensing bitter astringent taste intensity of green tea catechins. AB - To develop a methodology for creating a sensor with a receptor for specific taste substances, we focused on constructing a sensing system for the bitter-astringent taste intensity of green tea catechins: (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epicatechin-3-O-gallate (ECg), (-)-epigallocatechin (EGC), and (-) epicatechin (EC). (1)H NMR titration experiments revealed that beta-cyclodextrin was an adequate receptor for sensing the bitter-astringent taste intensity of catechins. A surface plasmon resonance (SPR) system immobilized beta-cyclodextrin indicated larger responses for the gallate-type catechins in comparison to the non-gallate-type catechins. These responses corresponded to the tendency of the bitter-astringent taste intensity of the catechins felt by humans. Furthermore, the SPR system detected the larger stability of the complex between the gallate type catechins and beta-cyclodextrin, which was interpreted as the aftertaste produced in humans by the gallate-type catechins. These results demonstrate that the beta-cyclodextrin/SPR system can sense the bitter-astringent taste intensity of the green tea catechins similar to human gustation. The methodology presented in this study can be used as a basic strategy for developing taste sensors with specific receptor functions. PMID- 20572675 TI - Cyclic structural motifs in 5,6-dihydroxyindole polymerization uncovered: biomimetic modular buildup of a unique five-membered macrocycle. AB - An unprecedented 5,6-dihydroxyindole macrocycle (4) featuring a rigid twisted backbone was obtained by biomimetic oxidative cross-coupling of the 2,2'-biindole 2 and triindole 3. A putative reaction intermediate, 2-quinone, was detected and characterized by pulse radiolysis and DFT calculations. Discovery of 4 indirectly supports for the first time theoretically predicted cyclic structural motifs as potential eumelanin building blocks. PMID- 20572676 TI - Azatripyrrolic and azatetrapyrrolic macrocycles from the Mannich reaction of pyrrole: receptors for anions. AB - Azatripyrrolic 1 and azatetrapyrrolic 2 macrocycles were synthesized in a single step by the Mannich reaction of pyrrole in the presence of primary amine hydrochloride and were structurally characterized among several other higher analogue azapyrrolic macrocycles. Binding constants for the halide anion complexes are determined by (1)H NMR titrations and they show different binding stoichiometries. PMID- 20572677 TI - Design and investigation of a series of rhodamine-based fluorescent probes for optical measurements of pH. AB - A series of structurally similar fluorescent probes (1-4), synthesized from rhodamine B, were designed to optically measure pH. Each probe had a unique "off on" response as the solution went from basic to acidic. Probes 1-3 exhibited a spirocyclic quenching of the pyronin B fluorophore, whereas probe 4 was quenched by PET from the amine moiety. PMID- 20572678 TI - Environmental effects dominate the folding of oligocholates in solution, surfactant micelles, and lipid membranes. AB - Oligocholate foldamers with different numbers and locations of guanidinium carboxylate salt bridges were synthesized. The salt bridges were introduced by incorporating arginine and glutamic acid residues into the foldamer sequence. The conformations of these foldamers were studied by fluorescence spectroscopy in homogeneous solution, anionic and nonionic micelles, and lipid bilayers. Environmental effects instead of inherent foldability were found to dominate the folding. As different noncovalent forces become involved in the conformations of the molecules, the best folder in one environment could turn into the worst in another. Preferential solvation was the main driving force for the folding of oligocholates in solution. The molecules behaved very differently in micelles and lipid bilayers, with the most critical factors controlling the folding-unfolding equilibrium being the solvation of ionic groups and the abilities of the surfactants/lipids to compete for the salt bridge. Because of their ability to fold into helices with a nonpolar exterior and a polar interior, the oligocholates could transport large hydrophilic molecules such as carboxyfluorescein across lipid bilayers. Both the conformational properties of the oligocholates and their binding with the guest were important to the transport efficiency. PMID- 20572681 TI - Communications: Accurate and efficient approximations to explicitly correlated coupled-cluster singles and doubles, CCSD-F12. AB - We propose a novel explicitly correlated coupled-cluster singles and doubles method CCSD(F12(*)), which retains the accuracy of CCSD-F12 while the computational costs are only insignificantly larger than those for a conventional CCSD calculation. PMID- 20572680 TI - Communications: Is quantum chemical treatment of biopolymers accurate? Intramolecular basis set superposition error (BSSE). AB - The accuracy of quantum chemical treatment of biopolymers by means of density functional theory is brought into question in terms of intramolecular basis set superposition error (BSSE). Secondary structure forms--beta-strands (C5; fully extended conformation), repeated gamma-turns (C7), 3(10)-helices (C10), and alpha helices (C13)--of homopolypeptides (polyglycine and polyalanine) are used as representative examples. The studied molecules include Ace(Gly)(5)NH(2), Ace(Gly)(10)NH(2), Ace(Ala)(5)NH(2), and Ace(Ala)(10)NH(2). The counterpoise correction procedure was found to produce reliable estimations for the BSSE values (other methods of BSSE correction are discussed). The calculations reported here used the B3LYP, PBE0 (PBE1PBE), and BMK density functionals with different basis sets [from 6-31G(d) to 6-311+G(3df,3pd)] to estimate the influence of basis set size on intramolecular BSSE. Calculation of BSSE was used to determine the deviation of the current results from the complete basis set limit. Intramolecular BSSE was found to be nonadditive with respect to biopolymer size, in contrast to claims in recent literature. The error, which is produced by a basis set superposition, was found to exceed 4 kcal mol(-1) when a medium-sized basis set was used. This indicates that this error has the same order of magnitude as the relative energy differences of secondary structure elements of biopolymers. This result makes all recent reports on the gas-phase stability of homopolypeptides and their analogs questionable. PMID- 20572682 TI - Communications: The fractional Stokes-Einstein equation: application to water. AB - Previously [K. R. Harris, J. Chem. Phys. 131, 054503 (2009)] it was shown that both real and model liquids fit the fractional form of the Stokes-Einstein relation [fractional Stokes-Einstein (FSE)] over extended ranges of temperature and density. For example, the self-diffusion coefficient and viscosity of the Lennard-Jones fluid fit the relation (D/T) = (1/eta)(t) with t = (0.921+/-0.003) and a range of molecular and ionic liquids for which high pressure data are available behave similarly, with t values between 0.79 and 1. At atmospheric pressure, normal and heavy water were also found to fit FSE from 238 to 363 K and from 242 to 328 K, respectively, but with distinct transitions in the supercooled region at about 258 and 265 K, respectively, from t = 0.94 (high temperature) to 0.67 (low temperature). Here the recent self-diffusion data of Yoshida et al. [J. Chem. Phys. 129, 214501 (2008)] for the saturation line are used to extend the high temperature fit to FSE to 623 K for both isotopomers. The FSE transition temperature in bulk water can be contrasted with much lower values reported in the literature for confined water. PMID- 20572679 TI - Is Nostoc H-NOX a NO sensor or redox switch? AB - Nostoc sp. (Ns) H-NOX is a heme protein found in symbiotic cyanobacteria, which has approximately 35% sequence identity and high structural homology to the beta subunit of soluble guanylyl cyclase (sGC), suggesting a NO sensing function. However, UV-vis, EPR, NIR MCD, and ligand binding experiments with ferrous and ferric Ns H-NOX indicate significant functional differences between Ns H-NOX and sGC. (1) After NO binding to sGC, the proximal histidine dissociates from the heme iron, causing a conformational change that triggers activation of sGC. In contrast, formation of pentacoordinate (5c) NO heme occurs to only a limited extent in Ns H-NOX, even at >1 mM NO. (2) Unlike sGC, two different hexacoordinate (6c) NO complexes are formed in Ns H-NOX with initial and final absorbance peaks at 418 and 414 nm, and the conversion rate is linearly dependent on [NO], indicating that a second NO binds transiently to catalyze formation of the 414 nm species. (3) sGC is insensitive to oxygen, and ferric sGC prepared by ferricyanide oxidation has a 5c high-spin heme complex. In contrast, Ns H-NOX autoxidizes in 24 h if exposed to air and forms a 6c ferric heme complex, indicating a major conformational change after oxidation and coordination by a second histidine side chain. Such a large conformational transition suggests that Ns H-NOX could function as either a redox or a NO sensor in the cyanobacterium. PMID- 20572683 TI - Assessing the accuracy of approximate treatments of ion hydration based on primitive quasichemical theory. AB - Quasichemical theory (QCT) provides a framework that can be used to partition the influence of the solvent surrounding an ion into near and distant contributions. Within QCT, the solvation properties of the ion are expressed as a sum of configurational integrals comprising only the ion and a small number of solvent molecules. QCT adopts a particularly simple form if it is assumed that the clusters undergo only small thermal fluctuations around a well-defined energy minimum and are affected exclusively in a mean-field sense by the surrounding bulk solvent. The fluctuations can then be integrated out via a simple vibrational analysis, leading to a closed-form expression for the solvation free energy of the ion. This constitutes the primitive form of quasichemical theory (pQCT), which is an approximate mathematical formulation aimed at reproducing the results from the full many-body configurational averages of statistical mechanics. While the results from pQCT from previous applications are reasonable, the accuracy of the approach has not been fully characterized and its range of validity remains unclear. Here, a direct test of pQCT for a set of ion models is carried out by comparing with the results of free energy simulations with explicit solvent. The influence of the distant surrounding bulk on the cluster comprising the ion and the nearest solvent molecule is treated both with a continuum dielectric approximation and with free energy perturbation molecular dynamics simulations with explicit solvent. The analysis shows that pQCT can provide an accurate framework in the case of a small cation such as Li(+). However, the approximation encounters increasing difficulties when applied to larger cations such as Na(+), and particularly for K(+). This suggests that results from pQCT should be interpreted with caution when comparing ions of different sizes. PMID- 20572684 TI - Ab initio floating occupation molecular orbital-complete active space configuration interaction: an efficient approximation to CASSCF. AB - We have implemented a complete active space configuration interaction method (CASCI) based on floating occupation molecular orbitals (FOMOs) at the ab initio level. The performance of this FOMO-CASCI method was investigated for potential applications in photochemistry and photodynamics. We found that FOMO-CASCI often represents a good approximation to the state-averaged complete active space self consistent field (SA-CASSCF) method. FOMO-CASCI is therefore an attractive alternative for use in ab initio photodynamics. The method is more efficient and more stable than SA-CASSCF. We also discuss some problematic cases for the FOMO CASCI approach. Possible extensions of the FOMO-CASCI approach are discussed briefly. PMID- 20572685 TI - Interlaced P3M algorithm with analytical and ik-differentiation. AB - The interlacing technique of Hockney and Eastwood is extended to the particle particle, particle-mesh (P3M) algorithm with analytical and ik-differentiation that computes the approximate Coulomb forces between N point particles in a periodic box. Interlacing means that one makes two separate computations of the reciprocal-space Ewald force, using two grids shifted with respect to each other by half of the diagonal of the grid subcell, and then takes the average of the two forces. The resulting algorithms compare favorably against their own noninterlaced versions and against the interlaced smooth particle-mesh Ewald algorithm. In our tests, the accuracy of the interlaced P3M methods was usually more than an order of magnitude higher than that of the other particle-mesh algorithms with the same parameter values. This accuracy gain can be converted into a speedup if the parameters of the algorithm are changed. Interlacing allows one to increase the grid spacing by up to a factor of 2 while keeping the same accuracy. A priori error estimates for the new algorithms are constructed, and the removal of the spurious self-force term is discussed. The success of interlacing is shown to be due to the fact that it suppresses the aliasing effects in the forces. It should be easy to incorporate the interlaced P3M algorithms into an existing simulation package, since this only requires a minor modification of the particle-mesh Ewald part of the code. PMID- 20572686 TI - Coulomb explosion in dicationic noble gas clusters: a genetic algorithm-based approach to critical size estimation for the suppression of Coulomb explosion and prediction of dissociation channels. AB - We present a genetic algorithm based investigation of structural fragmentation in dicationic noble gas clusters, Ar(n)(+2), Kr(n)(+2), and Xe(n)(+2), where n denotes the size of the cluster. Dications are predicted to be stable above a threshold size of the cluster when positive charges are assumed to remain localized on two noble gas atoms and the Lennard-Jones potential along with bare Coulomb and ion-induced dipole interactions are taken into account for describing the potential energy surface. Our cutoff values are close to those obtained experimentally [P. Scheier and T. D. Mark, J. Chem. Phys. 11, 3056 (1987)] and theoretically [J. G. Gay and B. J. Berne, Phys. Rev. Lett. 49, 194 (1982)]. When the charges are allowed to be equally distributed over four noble gas atoms in the cluster and the nonpolarization interaction terms are allowed to remain unchanged, our method successfully identifies the size threshold for stability as well as the nature of the channels of dissociation as function of cluster size. In Ar(n)(2+), for example, fissionlike fragmentation is predicted for n=55 while for n=43, the predicted outcome is nonfission fragmentation in complete agreement with earlier work [Golberg et al., J. Chem. Phys. 100, 8277 (1994)]. PMID- 20572687 TI - Time-dependent transport through molecular junctions. AB - We investigate transport properties of molecular junctions under two types of bias--a short time pulse or an ac bias--by combining a solution for Green's functions in the time domain with electronic structure information coming from ab initio density functional calculations. We find that the short time response depends on lead structure, bias voltage, and barrier heights both at the molecule lead contacts and within molecules. Under a low frequency ac bias, the electron flow either tracks or leads the bias signal (resistive or capacitive response) depending on whether the junction is perfectly conducting or not. For high frequency, the current lags the bias signal due to the kinetic inductance. The transition frequency is an intrinsic property of the junctions. PMID- 20572688 TI - A time-dependent semiempirical approach to determining excited states. AB - We study a time-dependent semiempirical method to determine excitation energies, TD-PM3. This semiempirical method allows large molecules to be treated. A Linear response Chebyshev approach yields the TD-PM3 spectrum very efficiently. Spectra and excitation energies were tested by comparing it with the results obtained using TD-DFT (Time Dependent-Density Functional Theory), using both small and large basis sets. They were also compared to PM3-CI, Time Dependent-Hartree Fock using the STO-3G basis set, and to experiment. TD-PM3 results generally match better the large-basis set calculations than the small-basis TD-DFT do; excitation energies are almost always accurate to within about 20% or less, except for a few small molecules. Accuracy improves as the molecules get larger. PMID- 20572689 TI - An algebraic proof of generalized Wick theorem. AB - The multireference normal order theory, introduced by Kutzelnigg and Mukherjee [J. Chem. Phys. 107, 432 (1997)], is defined explicitly, and an algebraic proof is given for the corresponding contraction rules for a product of any two normal ordered operators. The proof does not require that the contractions be cumulants, so it is less restricted. In addition, it follows from the proof that the normal order theory and corresponding contraction rules hold equally well if the contractions are only defined up to a certain level. These relaxations enable us to extend the original normal order theory. As a particular example, a quasi normal-order theory is developed, in which only one-body contractions are present. These contractions are based on the one-particle reduced density matrix. PMID- 20572690 TI - Modeling diffusion in restricted systems using the heat kernel expansion. AB - The averaged return-to-origin probability of finding a diffusing particle within a volume or in the neighborhood of the surface of a bounded region can be separated into a volume and a surface integral of the corresponding probability densities. However with the usual treatments (e.g., the commonly encountered diffusion propagator approach) there is no clear method to separate the integration of the diffusion propagators in each domain. Here we propose a general procedure based on applying the heat kernel expansion in restricted diffusion problems for the Green's function of the diffusion equation on an arbitrary region with an arbitrary boundary condition. We apply this method to the treatment of surface reaction rate in a sphere subject to the reflecting boundary condition. We determine that the rate of diffusion of a particle from the interior to the surface of the sphere changes by the square root of time plus some extra correction terms. Further, we are able to relate the diffusion propagator to the invariant properties of the region. Also in this approach we investigate how the heat kernel expansion can be applied to the problem of determining the return-to-origin probability, where we obtain a more precise result for the expansion of this probability in the case of a sphere. The advantage of this method lies in its generality and applicability to any geometrical boundary configuration and any kind of boundary condition. PMID- 20572691 TI - Two- and three-body interatomic dispersion energy contributions to binding in molecules and solids. AB - We present numerical estimates of the leading two- and three-body dispersion energy terms in van der Waals interactions for a broad variety of molecules and solids. The calculations are based on London and Axilrod-Teller-Muto expressions where the required interatomic dispersion energy coefficients, C(6) and C(9), are computed "on the fly" from the electron density. Inter- and intramolecular energy contributions are obtained using the Tang-Toennies (TT) damping function for short interatomic distances. The TT range parameters are equally extracted on the fly from the electron density using their linear relationship to van der Waals radii. This relationship is empiricially determined for all the combinations of He-Xe rare gas dimers, as well as for the He and Ar trimers. The investigated systems include the S22 database of noncovalent interactions, Ar, benzene and ice crystals, bilayer graphene, C(60) dimer, a peptide (Ala(10)), an intercalated drug-DNA model [ellipticine-d(CG)(2)], 42 DNA base pairs, a protein (DHFR, 2616 atoms), double stranded DNA (1905 atoms), and 12 molecular crystal polymorphs from crystal structure prediction blind test studies. The two- and three-body interatomic dispersion energies are found to contribute significantly to binding and cohesive energies, for bilayer graphene the latter reaches 50% of experimentally derived binding energy. These results suggest that interatomic three-body dispersion potentials should be accounted for in atomistic simulations when modeling bulky molecules or condensed phase systems. PMID- 20572692 TI - Methods for finding transition states on reduced potential energy surfaces. AB - Three new algorithms are presented for determining transition state (TS) structures on the reduced potential energy surface, that is, for problems in which a few important degrees of freedom can be isolated. All three methods use constrained optimization to rapidly find the TS without an initial Hessian evaluation. The algorithms highlight how efficiently the TS can be located on a reduced surface, where the rest of the degrees of freedom are minimized. The first method uses a nonpositive definite quasi-Newton update for the reduced degrees of freedom. The second uses Shepard interpolation to fit the Hessian and starts from a set of points that bound the TS. The third directly uses a finite difference scheme to calculate the reduced degrees of freedom of the Hessian of the entire system, and searches for the TS on the full potential energy surface. All three methods are tested on an epoxide hydrolase cluster, and the ring formations of cyclohexane and cyclobutenone. The results indicate that all the methods are able to converge quite rapidly to the correct TS, but that the finite difference approach is the most efficient. PMID- 20572693 TI - Correlation energy of two electrons in a ball. AB - We study the ground-state correlation energy E(c) of two electrons of opposite spin confined within a D-dimensional ball (D > or = 2) of radius R. In the high density regime, we report accurate results for the exact and restricted Hartree Fock energy, using a Hylleraas-type expansion for the former and a simple polynomial basis set for the latter. By investigating the exact limiting correlation energy E(c)(0) = lim(R-->0)E(c) for various values of D, we test our recent conjecture [P.-F. Loos and P. M. W. Gill, J. Chem. Phys. 131, 241101 (2009)] that in the large-D limit, E(c)(0) approximately -delta(2)/8 for any spherically symmetric confining external potential, where delta = 1/(D-1). PMID- 20572694 TI - Replication of noise-sustained autocatalytic chemical structures. AB - Autocatalytic systems in a differential-flow reactor may undergo a differential flow-induced chemical instability toward a convectively unstable regime, in which noise-sustained structures may appear. This is the case of a system with Gray Scott kinetics in a packed-bed reactor, as reported in [B. von Haeften and G. Izus, Phys. Rev. E 67, 056207 (2003)]. In this work, two identical copies of such a system are coupled in master-slave configuration and submitted to independent spatiotemporal Gaussian white noise sources. Numerical simulation of two dimensional reactors with uniform and Poiseuille flows reveals that the slave system replicates to a very high degree of precision and the convective patterns arising in the master one due to the presence of noise. The quality of this synchronization is assessed through several measures. A convective instability in the synchronization manifold is theoretically predicted and numerically confirmed. PMID- 20572695 TI - Structural manifestation of the delocalization error of density functional approximations: C(4N+2) rings and C(20) bowl, cage, and ring isomers. AB - The ground state structure of C(4N+2) rings is believed to exhibit a geometric transition from angle alternation (N < or = 2) to bond alternation (N > 2). All previous density functional theory (DFT) studies on these molecules have failed to reproduce this behavior by predicting either that the transition occurs at too large a ring size, or that the transition leads to a higher symmetry cumulene. Employing the recently proposed perspective of delocalization error within DFT we rationalize this failure of common density functional approximations (DFAs) and present calculations with the rCAM-B3LYP exchange-correlation functional that show an angle-to-bond-alternation transition between C(10) and C(14). The behavior exemplified here manifests itself more generally as the well known tendency of DFAs to bias toward delocalized electron distributions as favored by Huckel aromaticity, of which the C(4N+2) rings provide a quintessential example. Additional examples are the relative energies of the C(20) bowl, cage, and ring isomers; we show that the results from functionals with minimal delocalization error are in good agreement with CCSD(T) results, in contrast to other commonly used DFAs. An unbiased DFT treatment of electron delocalization is a key for reliable prediction of relative stability and hence the structures of complex molecules where many structure stabilization mechanisms exist. PMID- 20572696 TI - Fast computation of molecular random phase approximation correlation energies using resolution of the identity and imaginary frequency integration. AB - The random phase approximation (RPA) is an increasingly popular post-Kohn-Sham correlation method, but its high computational cost has limited molecular applications to systems with few atoms. Here we present an efficient implementation of RPA correlation energies based on a combination of resolution of the identity (RI) and imaginary frequency integration techniques. We show that the RI approximation to four-index electron repulsion integrals leads to a variational upper bound to the exact RPA correlation energy if the Coulomb metric is used. Auxiliary basis sets optimized for second-order Moller-Plesset (MP2) calculations are well suitable for RPA, as is demonstrated for the HEAT [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)] and MOLEKEL [F. Weigend et al., Chem. Phys. Lett. 294, 143 (1998)] benchmark sets. Using imaginary frequency integration rather than diagonalization to compute the matrix square root necessary for RPA, evaluation of the RPA correlation energy requires O(N(4) log N) operations and O(N(3)) storage only; the price for this dramatic improvement over existing algorithms is a numerical quadrature. We propose a numerical integration scheme that is exact in the two-orbital case and converges exponentially with the number of grid points. For most systems, 30-40 grid points yield muH accuracy in triple zeta basis sets, but much larger grids are necessary for small gap systems. The lowest-order approximation to the present method is a post-Kohn-Sham frequency-domain version of opposite-spin Laplace-transform RI-MP2 [J. Jung et al., Phys. Rev. B 70, 205107 (2004)]. Timings for polyacenes with up to 30 atoms show speed-ups of two orders of magnitude over previous implementations. The present approach makes it possible to routinely compute RPA correlation energies of systems well beyond 100 atoms, as is demonstrated for the octapeptide angiotensin II. PMID- 20572697 TI - Topology of cyclo-octane energy landscape. AB - Understanding energy landscapes is a major challenge in chemistry and biology. Although a wide variety of methods have been invented and applied to this problem, very little is understood about the actual mathematical structures underlying such landscapes. Perhaps the most general assumption is the idea that energy landscapes are low-dimensional manifolds embedded in high-dimensional Euclidean space. While this is a very mild assumption, we have discovered an example of an energy landscape which is nonmanifold, demonstrating previously unknown mathematical complexity. The example occurs in the energy landscape of cyclo-octane, which was found to have the structure of a reducible algebraic variety, composed of the union of a sphere and a Klein bottle, intersecting in two rings. PMID- 20572698 TI - General no-go condition for stochastic pumping. AB - The control of chemical dynamics requires understanding the effect of time dependent transition rates between states of chemomechanical molecular configurations. Pumping refers to generating a net current, e.g., per period in the time dependence, through a cycle of consecutive states. The work of artificial machines or synthesized molecular motors depends on it. In this paper we give short and simple proofs of no-go theorems, some of which appeared before but here with essential extensions to non-Markovian dynamics, including the study of the diffusion limit. It allows to exclude certain protocols in the working of chemical motors where only the depth of the energy well is changed in time and not the barrier height between pairs of states. We also show how pre-existing steady state currents are, in general, modified with a multiplicative factor when this time dependence is turned on. PMID- 20572699 TI - Quantum-dynamical consequences of the permutation symmetry of methyl groups. AB - We identify the nuclear spin isomers of nitromethane (CH(3)NO(2)) and discuss how symmetry arguments may be used to determine the spectrum and eigenfunctions of the spatial and spin-dependent Hamiltonians in an elegant way. Furthermore, we explore the effect of nuclear spin on the dynamics of the methyl group induced by a time-dependent magnetic field. We demonstrate that dipolar interactions between the protons can give rise to rotation of the methyl group and show within a one dimensional model and first order time-dependent perturbation theory that the induced motion is unidirectional and nuclear-spin selective. PMID- 20572700 TI - Toward elucidating the mechanism of femtosecond pulse shaping control in photodynamics of molecules by velocity map photoelectron and ion imaging. AB - The control of photofragmentation and ionization in a polyatomic molecule has been studied by femtosecond chirped laser pulse excitation and velocity map photoelectron and ion imaging. The experiments aimed at controlling and investigating the photodynamics in CH(2)BrCl using tunable chirped femtosecond pulses in the visible wavelength region 509-540 nm at maximum intensities of about 4x10(13) W/cm(2). We observe that the time-of-flight mass spectra as well as the photoelectron images can be strongly modified by manipulating the chirp parameter of ultrashort laser pulses. Specifically, a strong enhancement of the CH(2)Cl(+)/CH(2)BrCl(+) ion ratio by a factor of five and changes in the photoelectron spectra are observed for positively chirped pulses centered near 520 nm. These changes are only observed within a narrow window of wavelengths around 520 nm and only for positively chirped pulses. From the combination of the photoelectron spectra and the ion recoil energy of the CH(2)Cl(+) fragment we can deduce that the parent ionization and fragmentation is induced by a multiphoton excitation with five photons. The photoelectron images and the fragment ion images also provide the anisotropy (beta-parameter) of the various electron bands and fragment ions. We conclude that multiphoton excitation of the highest occupied 22a(') and 8a(") CH(2)BrCl molecular orbitals of Br-character are both involved in the five-photon ionization, however, only excitation of the 22a(') orbital appears to be (mostly) involved in the chirped control dynamics leading to enhanced fragmentation to CH(2)Cl(+)(X A(')) + Br((2)P(3/2)). We propose that a wavepacket following or a time-delay resonance mechanism between the two-photon excited n(x)(Br,22a(')) --> (2A(')) repulsive surface and the three-photon near resonant n(x)(Br,22a(')) --> Rydberg(A(')) state of the neutral CH(2)BrCl molecule is responsible for the enhanced excitation of the n(x)(Br,22a(')) molecular orbital with up-chirped pulses. This leads to enhanced ionization to a configuration in the CH(2)BrCl(+)(X A(')) continuum just above the dissociation limit of the CH(2)Cl(+) + Br((2)P(3/2)) channel, resulting in enhanced fragmentation. PMID- 20572701 TI - The Fock space method of vibrational analysis. AB - A reformulation of a semiclassical theory that presently seems uniquely capable of interpreting generic complex multiresonant vibrational spectra is presented. Once given the spectroscopic Hamiltonian which reveals the set of possible resonant couplings and its eigenstates, the new and old formulations both yield without any further computation level by level dynamical assignments for the spectra. Computing a simple trajectory in phase space reveals the motions that when quantized yield the assigned levels. The reformulation introduces two new projected representations of the wave functions. The first is in action space and the second in angle space. The projected representations often allow the reduced angle space, where nodal searches are made, to be of lower dimension than formally occurred. In addition the action representation is a similarly lower dimension lattice representation whose discreteness and regularity allow higher reduced dimensions to be studied. The lattice representation is used to produce a significantly more complete and detailed assignment of the thiophosgene spectrum than previously published. PMID- 20572702 TI - The permanent electric dipole moment of vanadium monosulfide. AB - A number of low-J lines of the C (4)Sigma(-) <-- X (4)Sigma(-) (0,0) band of a supersonic molecular beam sample of vanadium monosulfide (VS) have been recorded at a resolution of approximately 50 MHz by laser excitation spectroscopy. The electric field induced shift and splitting have been analyzed to give the permanent electric dipole moments mu of the C (4)Sigma(-)(upsilon = 0) and X (4)Sigma(-)(upsilon = 0) states as 2.38(13) and 5.16(5) D, respectively. An electrostatic model is used to predict mu for VS and VO. A molecular orbital correlation diagram is used to rationalize the trends in experimentally observed mu values of the 3d-monosulfides and 3d-monoxides. A comparison with theoretical predictions is made. PMID- 20572703 TI - Intermolecular potential energy surface of the water-carbon dioxide complex. AB - A complete intermolecular potential energy surface (PES) of the H(2)O-CO(2) complex has been constructed using a large scale ab initio calculations. This PES was sampled at 23,000 points of a five dimensional configuration space of the intermolecular coordinates. The interaction energy was calculated using the second order Moller-Plesset perturbation method in conjunction with the standard aug-cc-pVTZ basis set supplemented by bond functions. Single-point energy values were used to construct the analytical many-body representations of the PES that was further improved using a set of the interaction energy values calculated along the one-dimensional cuts of PES by employing the coupled cluster singles and doubles including connected triples method. The accurate data on the structure and energetics of the complex considered have been reported. The analysis of the PES determined revealed its complex structure. A few bifurcations were found on the minimum energy paths along the coordinates describing the radial and angular motions. For the torsional motion, four symmetrically equivalent potential barriers were found as a consequence of the bifurcations, so earlier models of this motion assuming two equivalent potential barriers were justified only for the lowest torsional states. PMID- 20572704 TI - High resolution mass analysis of N- and C-terminal negative ions resulting from resonance electron capture by aliphatic amino acids. AB - High mass resolving power was applied to study resonance electron capture by glycine, alanine, and valine, and accurate mass measurements helped to distinguish between some negative ions having the same nominal masses. It was established that the C- and N-terminal negative ions of the same nominal masses were formed at different electron energies from different resonance states. The typical fragmentation pathways in deprotonated amino acids via loss of water initiated by collisional activation were not observed upon resonant electron capture by aliphatic amino acids. Instead, [M-18](-) negative ions in the vicinity of 5 eV were found to be associated with simultaneous loss of either ammonia and a hydrogen atom or an amino group and a hydrogen molecule. PMID- 20572706 TI - Potential energy surface for spin-polarized rubidium trimer. AB - Potential energy surface for the lowest quartet state of the rubidium trimer is constructed, making use of the many-body decomposition. Interaction energies are calculated using the coupled-clusters method and interpolated using the reciprocal-power reproducing kernel Hilbert space interpolation method. Both the two-body and three-body nonadditive parts are extrapolated to exhibit the correct long-range behavior. Consequences for the low-energy scattering are briefly discussed. PMID- 20572705 TI - Ionization of doped helium nanodroplets: complexes of C60 with water clusters. AB - Water clusters are known to undergo an autoprotonation reaction upon ionization by photons or electron impact, resulting in the formation of (H(2)O)(n)H(3)O(+). Ejection of OH cannot be quenched by near-threshold ionization; it is only partly quenched when clusters are complexed with inert gas atoms. Mass spectra recorded by electron ionization of water-doped helium droplets show that the helium matrix also fails to quench OH loss. The situation changes drastically when helium droplets are codoped with C(60). Charged C(60)-water complexes are predominantly unprotonated; C(60)(H(2)O)(4)(+) and (C(60))(2)(H(2)O)(4)(+) appear with enhanced abundance. Another intense ion series is due to C(60)(H(2)O)(n)OH(+); dehydrogenation is proposed to be initiated by charge transfer between the primary He(+) ion and C(60). The resulting electronically excited C(60)(+*) leads to the formation of a doubly charged C(60)-water complex either via emission of an Auger electron from C(60)(+*), or internal Penning ionization of the attached water complex, followed by charge separation within {C(60)(H(2)O)(n)}(2+). This mechanism would also explain previous observations of dehydrogenation reactions in doped helium droplets. Mass-analyzed ion kinetic energy scans reveal spontaneous (unimolecular) dissociation of C(60)(H(2)O)(n)(+). In addition to the loss of single water molecules, a prominent reaction channel yields bare C(60)(+) for sizes n=3, 4, or 6. Ab initio Hartree-Fock calculations for C(60)-water complexes reveal negligible charge transfer within neutral complexes. Cationic complexes are well described as water clusters weakly bound to C(60)(+). For n=3, 4, or 6, fissionlike desorption of the entire water complex from C(60)(H(2)O)(n)(+) energetically competes with the evaporation of a single water molecule. PMID- 20572707 TI - Ab initio calculations on the X (2)B1 and A (2)A1 states of AsH2, and Franck Condon simulation, including anharmonicity, of the A(0,0,0)-X single vibronic level emission spectrum of AsH2. AB - Restricted-spin coupled-cluster single-double plus perturbative triple excitation {RCCSD(T)} calculations were carried out on the X (2)B(1) and A (2)A(1) states of AsH(2) employing the fully relativistic small-core effective core potential (ECP10MDF) for As and basis sets of up to the augmented correlation-consistent polarized valence quintuple-zeta (aug-cc-pV5Z) quality. Minimum-energy geometrical parameters and relative electronic energies were evaluated, including contributions from extrapolation to the complete basis set limit and from outer core correlation of the As 3d(10) electrons employing additional tight 4d3f2g2h functions designed for As. In addition, simplified, explicitly correlated CCSD(T) F12 calculations were also performed employing different atomic orbital basis sets of up to aug-cc-pVQZ quality, and associated complementary auxiliary and density-fitting basis sets. The best theoretical estimate of the relative electronic energy of the A (2)A(1) state of AsH(2) relative to the X (2)B(1) state including zero-point energy correction (T(0)) is 19,954(32) cm(-1), which agrees very well with available experimental T(0) values of 19,909.4531(18) and 19,909.4910(17) cm(-1) obtained from recent laser induced fluorescence and cavity ringdown absorption spectroscopic studies. In addition, potential energy functions (PEFs) of the X (2)B(1) and A (2)A(1) states of AsH(2) were computed at different RCCSD(T) and CCSD(T)-F12 levels. These PEFs were used in variational calculations of anharmonic vibrational wave functions, which were then utilized to calculate Franck-Condon factors (FCFs) between these two states, using a method which includes allowance for anharmonicity and Duschinsky rotation. The A(0,0,0)-X single vibronic level (SVL) emission spectrum of AsH(2) was simulated using these computed FCFs. Comparison between simulated and available experimental vibrationally resolved spectra of the A(0,0,0)-X SVL emission of AsH(2), which consist essentially of the bending (2(n)) series, suggests that there is a significant loss in intensity in the low emission energy region of the experimental spectrum. PMID- 20572708 TI - Relativistic four- and two-component calculations of parity violation effects in chiral tungsten molecules of the form NWXYZ (X, Y, Z = H, F, Cl, Br, or I). AB - Parity violation (PV) effects to the electronic ground state structure for a series of chiral tungsten molecules of the type NWXYZ (X, Y, Z = H, F, Cl, Br, or I) are compared using four- (Dirac) and two- (X2C) component relativistic Hartree Fock and density functional theories. The results show the computationally more affordable two-component X2C approach yields accurate results for all molecules investigated. The PV energy differences between the two enantiomers range from as little as 0.4 Hz for NWClBrI to 140 Hz for NWHClI using a generalized gradient approximation including exact exchange (B3LYP). The W-N stretching mode in these molecules lies in the experimentally favorable CO(2) laser frequency range, and we therefore investigated PV effects in vibrational transitions using a single normal mode analysis. Here the PV frequency shift between the two enantiomers ranges from 1.6 mHz for NWFBrI to 710 mHz for NWHClI. Thus these types of molecules could be useful for the future detection of PV effects in chiral molecules. PMID- 20572709 TI - A theoretical analysis of time-dependent fragment momenta in indirect photofragmentation. AB - We study theoretically diatomic molecules which are prepared in a superposition of quasibound resonance states by a femtosecond laser pulse. An analytical (Landau-Zener-like) result is derived for the momentum distribution of the atomic fragments in the asymptotic force-free region after a single passage of a curve crossing. Furthermore, at later times, simple analytical expressions show how the emerging structures in the momentum distribution are related to the energies of the resonance states. PMID- 20572710 TI - Permanent electric dipole moment of copper monoxide, CuO. AB - A number of low-rotational lines of the A (2)Sigma(-) <-- X (2)Pi(3/2)(0,0) subband of a molecular beam of copper monoxide, CuO, were recorded field free and in the presence of a static electric field. A set of optimized fine and hyperfine parameters for the A (2)Sigma(-)(upsilon(') = 0) state was produced from the analysis of the field-free spectrum. The permanent electric dipole moments mu for the A (2)Sigma(-)(upsilon = 0) and X (2)Pi(3/2)(upsilon = 0) states were determined to be 1.12(71) and 4.57(3) D, respectively, from the analysis of the observed Stark shifts. The error of the experimentally determined mu value for the X (2)Pi(3/2)(upsilon = 0) state is approximately ten times less than that for the previously determined value: mu = 4.45(30) D [T. C. Steimle et al., J. Chem. Phys. 87, 5670 (1987)]. The experimental mu values are compared with theoretical predictions. PMID- 20572711 TI - A femtosecond velocity map imaging study on B-band predissociation in CH3I. I. The band origin. AB - A femtosecond pump-probe experiment, coupled with velocity map ion imaging, is reported on the second absorption band (B-band) of CH(3)I. The measurements provide a detailed picture of real-time B-band predissociation in the band origin at 201.2 nm. Several new data are reported. (i) A value of 1.5+/-0.1 ps has been obtained for the lifetime of the excited state, consistent within errors with the only other direct measurement of this quantity [A. P. Baronavski and J. C. Owrutsky, J. Chem. Phys. 108, 3445 (1998)]. (ii) It has been possible to measure the angular character of the transition directly through the observation of fragments appearing early with respect to both predissociation lifetime and molecular rotation. (iii) Vibrational activity in CH(3) has been found, both in the umbrella (nu(2)) and the symmetric stretch (nu(1)) modes, with estimates of relative populations. All these findings constitute a challenge and a test for much-wanted high level ab initio and dynamics calculations in this energy region. PMID- 20572712 TI - A time-independent Hermitian Floquet approach for high harmonic generation in H(2)+ and HD+: effect of nonadiabatic interaction in HD+. AB - We have theoretically investigated the high harmonic generation (HHG) in H(2)(+) and HD(+) using a time-independent Hermitian nonperturbative three-dimensional Floquet approach for continuous wave monochromatic lasers of intensities of 2.59x10(13), 4.0x10(13), and 5.6x10(13) W/cm(2), and wavelengths of 1064, 532, and 355 nm. For the moderate intensities and the wavelengths used, the Keldysh parameter gamma > 1 and no tunnel ionization occurs. We have endeavored to explain the dynamics of HHG in H(2)(+) and HD(+) within the framework of transitions due to electronic as well as intrinsic (for HD(+)) dipole moments and the nuclear motion on the field coupled ground and the first excited electronic states of these single-electron molecular ions, without considering any ionization. To evaluate the HHG spectra, the resonance Floquet quasienergy and the Fourier components of the Floquet state corresponding to the initial vibrational-rotational level v = 0, J = 0 have been calculated by solving the time-independent close-coupled Schrodinger equation following the Floquet ansatz. For HD(+), we have taken into account the symmetry breaking effect of the nonadiabatic interaction or coupling [beyond the Born-Oppenheimer (BO) dynamics] in our calculations of the HHG spectra and have compared the results with the HHG spectra of HD(+) obtained with the BO approximation. PMID- 20572713 TI - Finite-temperature quantum simulations of mixed rare gas clusters. AB - Finite-temperature quantum Monte Carlo simulations are presented for mixed neon/argon rare gas clusters containing up to n=10 atoms. For the smallest clusters (n=3) comparison with rigorous bound state calculations and experiments shows that the present approach is accurate to within fractions of wavenumbers for energies and to within a few percent or better for rotational constants. For larger cluster sizes, for which no rigorous quantum calculations are available, comparison with experiment becomes even more favorable. In all simulations accurate pair potentials for the rare gas-rare gas interactions are employed and comparison with high-level electronic structure calculations suggest that many body interactions play a minor role. For the largest clusters investigated (Ne(4)Ar(6)) gradual melting of the neon phase is observed while the argon-phase remains structurally intact. PMID- 20572714 TI - Multidimensional steric effect for the XeBr* (B, C) formation in the oriented Xe*((3)P2, M(J) = 2) + oriented CF3Br reaction. AB - Steric effect for the XeBr(*) (B, C) formation in the oriented Xe(*)((3)P(2), M(J) = 2) + oriented CF(3)Br reaction has been observed as a function of the mutual configuration between the molecular orientation and the atomic orientation in the collision frame. Molecular steric opacity function has been determined as a function of the atomic orbital alignment (L(Z)(')) in the collision frame. The L(Z)(') selectivity in the molecular steric opacity function is different between the XeBr(*) (B, C) channels: For the XeBr(*) (C) channel, the L(Z)(') = 0 alignment is favorable at the molecular axis direction and the absolute value(L(Z)(')) = 1 alignment is favorable at the sideway direction, whereas for the XeBr(*) (B) channel, the L(Z)(') = 0 alignment is favorable at the sideway direction and the absolute value(L(Z)(')) = 1 alignment is favorable at the molecular axis direction. However, the shape of the steric opacity function for the XeBr(*) (B) channel at the L(Z)(') = 0 (and absolute value(L(Z)(')) = 1) alignment is similar to that for the XeBr(*) (C) channel at the absolute value(L(Z)(')) = 1 (and L(Z)(') = 0) alignment, respectively: A large molecular orientation dependence (i.e., the largest reactivity at the Br-end with the small molecular alignment dependence) is recognized for the XeBr(*) (B) channel at the L(Z)(') = 0 alignment and for the XeBr(*) (C) channel at the absolute value(L(Z)(')) = 1 alignment, whereas a large molecular alignment dependence (i.e., the largest reactivity at the Br-end with the poor reactivity at the sideway) is recognized for the XeBr(*) (B) channel at the absolute value(L(Z)(')) = 1 alignment and for the XeBr(*) (C) channel at the L(Z)(') = 0 alignment. We propose the indirect mechanism for the dark channels (Xe + Br + CF(3)) via the back-electron transfer from the CF(3) segment (or dissociating CF(3)...Br(-)) to Xe(+) as the origin of the significant molecular alignment dependence in the molecular steric opacity function. PMID- 20572715 TI - Dimerization-assisted energy transport in light-harvesting complexes. AB - We study the role of the dimer structure of light-harvesting complex II (LH2) in excitation transfer from the LH2 [without a reaction center (RC)] to the LH1 (surrounding the RC) or from the LH2 to another LH2. The excited and unexcited states of a bacteriochlorophyll (BChl) are modeled by a quasispin. In the framework of quantum open system theory, we represent the excitation transfer as the total leakage of the LH2 system and then calculate the transfer efficiency and average transfer time. For different initial states with various quantum superposition properties, we study how the dimerization of the B850 BChl ring can enhance the transfer efficiency and shorten the average transfer time. PMID- 20572716 TI - Equilibrium self-assembly of colloids with distinct interaction sites: thermodynamics, percolation, and cluster distribution functions. AB - We calculate the equilibrium thermodynamic properties, percolation threshold, and cluster distribution functions for a model of associating colloids, which consists of hard spherical particles having on their surfaces three short-ranged attractive sites (sticky spots) of two different types, A and B. The thermodynamic properties are calculated using Wertheim's perturbation theory of associating fluids. This also allows us to find the onset of self-assembly, which can be quantified by the maxima of the specific heat at constant volume. The percolation threshold is derived, under the no-loop assumption, for the correlated bond model: In all cases it is two percolated phases that become identical at a critical point, when one exists. Finally, the cluster size distributions are calculated by mapping the model onto an effective model, characterized by a--state-dependent--functionality f and unique bonding probability p. The mapping is based on the asymptotic limit of the cluster distributions functions of the generic model and the effective parameters are defined through the requirement that the equilibrium cluster distributions of the true and effective models have the same number-averaged and weight-averaged sizes at all densities and temperatures. We also study the model numerically in the case where BB interactions are missing. In this limit, AB bonds either provide branching between A-chains (Y-junctions) if epsilon(AB)/epsilon(AA) is small, or drive the formation of a hyperbranched polymer if epsilon(AB)/epsilon(AA) is large. We find that the theoretical predictions describe quite accurately the numerical data, especially in the region where Y-junctions are present. There is fairly good agreement between theoretical and numerical results both for the thermodynamic (number of bonds and phase coexistence) and the connectivity properties of the model (cluster size distributions and percolation locus). PMID- 20572718 TI - Spectral line shape profile of rovibrational transitions of CO embedded in p-H2 crystals studied by high resolution IR diode laser spectroscopy. AB - Line profiles of rovibrational transitions of CO embedded in p-H(2) crystals were studied by high resolution midinfrared diode laser spectroscopy. The line profile analysis for the R(0)(parallel), R(0)(perpendicular), P(1)(parallel), and P(1)(perpendicular) transitions shows that spectral line shapes are well reproduced by a convolution of Gaussian and Lorentzian functions. The temperature dependence of the Lorentzian Gamma(L)(T) and Gaussian widths Gamma(G)(T) shows that there is a nonzero linewidth contribution to each at the T = 0 K limit. The main part of the Lorentzian width Gamma(L)(T = 0) shows anisotropy in the hcp structure and is explained by spontaneous decay of the rotational excited state energy to phonon modes. A smaller part of Gamma(L)(T = 0) is attributed to inhomogeneous broadening due to the point defects of other CO molecules in the crystal. On the other hand, the Gaussian width Gamma(G)(T = 0) is explained by inhomogeneous broadening due to dislocations. In the T > 0 region, Gamma(L)(T) shows strong temperature dependence but Gamma(G)(T) does not. The center frequencies of the R(0)(perpendicular) and P(1)(parallel) transitions show blueshifts and those of the R(0)(parallel) and P(1)(perpendicular) transitions show redshifts with increasing temperature. This phenomenon is explained by a decrease in the anisotropy in the crystal field, which is caused by the averaging of thermal lattice fluctuations. Furthermore, the contribution of vibration and rotation to the linewidth is discussed. PMID- 20572717 TI - Temporal effects on spectroscopic line shapes, resolution, and sensitivity of the broad-band sum frequency generation. AB - Sum frequency generation (SFG) is a surface-selective spectroscopy that provides a wealth of molecular-level information on the structure and dynamics at surfaces and interfaces. This paper addresses the general issue of spectral resolution and sensitivity of the broad-band (BB) SFG that involves a spectrally narrow nonresonant (usually visible) and a BB resonant (usually infrared) laser pulses. We examine how the spectral width and temporal shape of the two pulses, and the time delay between them, relate to the spectroscopic line shape and signal level in the BB-SFG measurement. By combining experimental and model calculations, we show that the best spectral resolution and highest signal level are simultaneously achieved when the nonresonant narrow-band upconversion pulse arrives with a nonzero time delay after the resonant BB pulse. The nonzero time delay partially avoids the linear trade-off of improving spectral resolution at the expense of decreasing signal intensity, which is common in BB-SFG schemes utilizing spectral filtering to produce narrow-band visible pulses. PMID- 20572719 TI - Crystal nucleation rate isotherms in Lennard-Jones liquids. AB - We present the results of molecular dynamics simulations of the crystal nucleation rate in a supercooled Lennard-Jones liquid. The nucleation rate as a function of the pressure has been calculated by the method of determining the expectation time for liquid crystallization at temperatures higher than that of the triple point (T(*) = 0.865), close to the temperature of the terminal critical point of the metastable extension of the melting curve (T(*) = 0.55) and below this temperature (T(*) = 0.4). In computer experiments the nucleation rate varied from 10(32) to 10(35) s(-1) m(-3). The dimensions of critical nuclei and the pressure inside them, the surface free energy at a critical crystal nucleus liquid interface, the height of the nucleation barrier, and the Zeldovich factor have been determined from the results of molecular dynamics simulations and their comparison with classical homogeneous nucleation theory. It is shown that the surface free energy at a curved crystal-liquid interface, as distinct from a flat interface, has also been determined at temperatures lower than the temperature of the terminal critical point of the melting curve and is a monotonically increasing function of the temperature. PMID- 20572720 TI - Generalized mean spherical approximation for the multicomponent restricted primitive model. AB - The generalized mean spherical approximation of Stell and Sun [J. Chem. Phys. 63, 5333 (1975)] for the binary charge-symmetric restricted primitive model (electroneutral mixture of equally sized hard spheres) is extended to charge asymmetric binary electrolytes and to the generally multicomponent, but still restricted (i.e., equally sized) primitive model. PMID- 20572721 TI - Tetrahedral order, pair correlation entropy, and waterlike liquid state anomalies: comparison of GeO2 with BeF2, SiO2, and H2O. AB - Molecular dynamics simulations of the Oeffner-Elliot model of germania (GeO(2)) are performed to identify nested regions of anomalous behavior in structural order, diffusivity, and pair entropy in the density-temperature plane, analogous to that seen in BeF(2), SiO(2), and H(2)O. The decreasing constraint of local tetrahedrality in GeO(2), compared to SiO(2) and BeF(2), substantially lowers the onset temperatures for anomalous behavior relative to the experimental melting temperatures (T(m)). Germania resembles water, more strongly than the ionic melts, in terms of temperatures for onset of anomalous behavior as well as in the order maps; for example, the structural anomaly sets in at 3.42T(m) in BeF(2), 3.09T(m) in SiO(2), 1.43T(m) in GeO(2), and 1.21T(m) in H(2)O. The detailed shapes of the anomalous regimes vary for different systems but the relative temperatures of onset for different anomalies are very similar in the different systems. The pair correlation entropy is shown to be a crucial and experimentally accessible quantity for relating structure, entropy, and diffusivity that could be potentially useful for a large class of inorganic ionic liquids. PMID- 20572722 TI - Solvatochromic shift of phenol blue in water from a combined Car-Parrinello molecular dynamics hybrid quantum mechanics-molecular mechanics and ZINDO approach. AB - The present work addresses the solvatochromic shift of phenol blue (PB) dye. For this purpose the results of Car-Parrinello molecular dynamics (CPMD) simulations for PB in gas phase are compared with results obtained for PB in water from CPMD hybrid quantum mechanics-molecular mechanics (CPMD-QM/MM) calculations. The absorption spectra were obtained using the intermediate neglect of differential overlap/spectroscopic-configuration interaction (INDO/CIS) method and were calculated for a multitude of configurations of the trajectory. The calculated lambda(max) for PB in gas phase was found to be about 535 nm, which is considerably lower than the lambda(max) reported for PB in nonpolar solvents. Different solvation shells for PB in water have been defined based on the solute all-atoms and solvent center of mass radial distribution function (g(r(X-O))). The electronic excitation energies for PB computed in the presence of solvent molecules in an increasing number of solvation shells were calculated in a systematic way to evaluate their contributions to the solvatochrmic shift. The inclusion of solvent molecules in the hydration shell yields a lambda(max) of 640 nm, which contributes to almost 78% of the solvatochromic shift. The inclusion of solvent molecules up to 10 A in the g(r(X-O)) rdf yields a lambda(max) of 670 nm which is in good agreement with the experimentally reported value of 654-684 nm. Overall, the present study suggests that the combined CPMD-QM/MM and INDO-CIS approach can be used successfully to model solvatochromic shifts of organic dye molecules. PMID- 20572723 TI - Entropy, diffusivity and the energy landscape of a waterlike fluid. AB - Molecular dynamics simulations and instantaneous normal mode (INM) analysis of a fluid with core-softened pair interactions and waterlike liquid-state anomalies are performed to obtain an understanding of the relationship between thermodynamics, transport properties, and the potential energy landscape. Rosenfeld scaling of diffusivities with the thermodynamic excess and pair correlation entropy is demonstrated for this model. The INM spectra are shown to carry information about the dynamical consequences of the interplay between length scales characteristic of anomalous fluids, such as bimodality of the real and imaginary branches of the frequency distribution. The INM spectral information is used to partition the liquid entropy into two contributions associated with the real and imaginary frequency modes; only the entropy contribution from the imaginary branch captures the nonmonotonic behavior of the excess entropy and diffusivity in the anomalous regime of the fluid. PMID- 20572724 TI - The influence of water on the structural and transport properties of model ionic liquids. AB - Molecular dynamics simulations are used to investigate the influence of water on model ionic liquids. Several models, where the ions vary in size, and in the location of the charge with respect to the center of mass, are considered. Particular attention is focused on the variation in transport properties (diffusion coefficients, shear viscosity, and electrical conductivity) with water concentration. An effort is made to identify the underlying physical reasons for water's influence. The results for our model ionic liquids fall loosely into two categories, depending on the molecular characteristics of the constituent ions. If the ion size disparity is not too large (cation:anion diameter ratio < or approximately 2:1), and if the ion charge location is such that directional ion pair bonds are relatively weak, then we find that the ionic diffusion coefficients and the electrical conductivity increase, and the viscosity decreases with increasing water concentration. This agrees with what is commonly observed experimentally for room temperature ionic liquids (RTILs). For these systems, we do not find changes in the equilibrium structure that can account for the strong influence of water on the transport properties. Rather, by varying the molecular mass of water in our simulations, we demonstrate that the dominant effect of water can be dynamical in origin. In RTIL-water mixtures, the molecular mass of water is generally much less than that of the ions it replaces. These lighter water molecules tend to displace much heavier counterions from the ion coordination shells. This reduces caging and increases the diffusivity, which leads to higher conductivities and lower viscosities. For models with a larger ion size disparity (3:1), or in charge-off-center systems, where strong directional ion pairs are important in the pure ionic liquid, the behavior can be quite different. In these systems, the diffusion coefficients and electrical conductivity can still display conventional behavior and increase when water is added even though the reasons for this can be more complex than in the simpler cases noted above. However, in these systems the viscosity can increase, sometimes quite steeply, with increasing water concentration. We trace this unusual behavior to the formation of associated structures, extended anion-water chains that can weave among the cations in the size disparate case, and strongly bound cation-water-anion clusters in the charge-off-center systems. PMID- 20572725 TI - The stability of a crystal with diamond structure for patchy particles with tetrahedral symmetry. AB - The phase diagram of model anisotropic particles with four attractive patches in a tetrahedral arrangement has been computed at two different values of the range of the potential, with the aim of investigating the conditions under which a diamond crystal can be formed. We find that the diamond phase is never stable for our longer-ranged potential. At low temperatures and pressures, the fluid freezes into a body-centered-cubic solid that can be viewed as two interpenetrating diamond lattices with a weak interaction between the two sublattices. Upon compression, an orientationally ordered face-centered-cubic crystal becomes more stable than the body-centered-cubic crystal, and at higher temperatures, a plastic face-centered-cubic phase is stabilized by the increased entropy due to orientational disorder. A similar phase diagram is found for the shorter-ranged potential, but at low temperatures and pressures, we also find a region over which the diamond phase is thermodynamically favored over the body-centered-cubic phase. The higher vibrational entropy of the diamond structure with respect to the body-centered-cubic solid explains why it is stable even though the enthalpy of the latter phase is lower. Some preliminary studies on the growth of the diamond structure starting from a crystal seed were performed. Even though the diamond phase is never thermodynamically stable for the longer-ranged model, direct coexistence simulations of the interface between the fluid and the body centered-cubic crystal and between the fluid and the diamond crystal show that at sufficiently low pressures, it is quite probable that in both cases the solid grows into a diamond crystal, albeit involving some defects. These results highlight the importance of kinetic effects in the formation of diamond crystals in systems of patchy particles. PMID- 20572726 TI - Molecular model for carbon dioxide optimized to vapor-liquid equilibria. AB - A molecular model for carbon dioxide is presented, and the parameters of the Lennard-Jones sites, the bond length, and the quadrupole moment are optimized to experimental vapor-liquid equilibrium data. The resulting molecular model shows mean unsigned deviations to the experiment over the whole temperature range from triple point to critical point of 0.4% in saturated liquid density, 1.8% in vapor pressure, and 8.1% in enthalpy of vaporization. The molecular model is assessed by comparing predicted thermophysical properties with experimental data and a reference equation of state for a large part of the fluid region. The average deviations for density and residual enthalpy are 4.5% and 1.7%, respectively. The model is also capable to predict the radial distribution function, the second virial coefficient, and transport properties, the average deviations of the latter are 12%. PMID- 20572727 TI - Vibrational absorption, vibrational circular dichroism, and theoretical studies of methyl lactate self-aggregation and methyl lactate-methanol intermolecular interactions. AB - The infrared vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl lactate in carbon tetrachloride and methanol have been measured in the 1000-1800 cm(-1) region. Noticeable changes due to the solute self aggregation and solvent-solute intermolecular hydrogen-bonding interactions have been detected in the reported spectra of the 2M methyl lactate solution in CCl(4) and in methanol, respectively. Molecular dynamics simulations and a series of density functional theory (DFT) B3LYP/6-311++G(**)) and single point MP2/6 311++G(**) energy calculations have been performed to identify and to model the explicit hydrogen-bonding interactions between the methanol solvent and the methyl lactate solute and among the methyl lactate molecules. Geometry search and optimization have been performed for the most stable conformers of the methyl lactate dimer and the methyl lactate-(methanol)(N) clusters, with N=1, 2, and 3. The relative single point MP2 energies among conformers are noticeably different from those obtained with DFT for the larger methyl lactate-methanol complexes. The VA and VCD spectra of these complexes have been simulated and compared to the corresponding experimental spectra. From the combined experimental and theoretical VA and VCD studies, it has been identified that both the methyl lactate monomer and dimer are the main species in the 2M CCl(4) solution with 65% and 35% relative abundances, respectively, while the binary (55%) and quaternary (30%) methyl lactate-methanol clusters dominate in the 2M methanol solution, together with a smaller amount (15%) of the methyl lactate monomer. The effects of solute self-aggregation and solute-solvent interactions have been investigated in detail. PMID- 20572729 TI - Obtaining molecular orientation from second harmonic and sum frequency scattering experiments in water: angular distribution and polarization dependence. AB - We present a method for determining molecular orientation from second-order nonlinear light scattering experiments. Our modeling shows that there is an optimal angular region, for which the scattering pattern is most sensitive to molecular orientation. We show that molecular orientation can be retrieved from measuring intensities at different polarization combinations, measuring the relative amplitudes of different vibrational modes of the same moiety and by analyzing the shape of the angular scattering pattern. We further show that for C(2v) and C(3v) point groups, the asymmetric stretch mode displays a higher sensitivity to molecular orientation than the corresponding symmetric mode. We have implemented the model in an interactive simulation program that may be found at http://www.mf.mpg.de/en/abteilungen/roke/simulation.html. PMID- 20572728 TI - X-ray absorption and luminescence studies of Ba2Ca(BO3)2: Ce3+/Na+ phosphors. AB - X-ray excited optical luminescence (XEOL) spectroscopy has been used to investigate the optical emission properties of Ce(3+) activated Ba(2)Ca(BO(3))(2) with a charge-compensating Na(+) and the results are compared with the optical emission properties from UV excitation. Further, x-ray absorption near-edge structure (XANES) has been employed to study the chemical environment and energy transfer efficiency to optical emission upon x-ray excitation. XEOL results agree well with optical emission with UV excitation. XANES results across various absorption edges show that while the chemical environment of host materials does not change significantly with doping, luminescence yield decreases significantly at absorption edges due to an abrupt change in the de-excitation mechanism. PMID- 20572730 TI - Structures of gas-phase Ag-Pd nanoclusters: a computational study. AB - Gas-phase Ag-Pd clusters in the size range of 38-100 atoms are studied via a combined density-functional/empirical-potential (DF-EP) approach. Many-body EPs describing Pd-Pd, Ag-Ag, and Ag-Pd interactions are reparametrized and used in thorough global optimization searches at sizes N=38, 60, and 100 and compositions 25%, 50%, and 75%. The results are analyzed in terms of structural families, whose lowest-energy isomers are reoptimized at the DF level to investigate the crossover among structural motifs. It is found that the reparametrized EPs show a better qualitative and quantitative agreement with DF results when compared to the original potentials taken from literature: Both methods agree on which is the lowest-energy isomer at each size and composition, and the energy differences in the various isomers are in good qualitative agreement, especially for 60- and 100 atom clusters. The reparametrized potentials should thus be applicable to large clusters, where DF calculations are not feasible any more. PMID- 20572731 TI - First-principles study of Ru atoms and clusters adsorbed outside and inside carbon nanotubes. AB - First-principles calculations were performed to investigate the binding energies, geometric structures, and electronic properties of 4d transition metal (TM) (particularly, Ru), atoms, and clusters adsorbed outside/inside the single-walled or double-walled carbon nanotubes. The equilibrium adsorption structures of the TM atoms depend on the valence electron configuration of the metal atoms. Due to curvature effect, all TM atoms adsorbed inside and outside (6, 6) carbon nanotubes donate different amounts of electrons to the nanotube, with a nearly constant difference of about 0.5 electrons/TM atom. The analysis of electronic density of states revealed hybridization between the p electrons from C and the d electrons from Ru, which results in charge transfer from metal to carbon. The amount of charge transfer shows systematical trend with the electronegativity of 4d TMs. When Ru atom or cluster adsorbs on double-walled nanotubes, the effect of charge transfer is slightly enhanced with regard to the single-walled nanotubes. PMID- 20572732 TI - Computational analysis of binary segregation during colloidal crystallization with DNA-mediated interactions. AB - A detailed computational study of compositional segregation during growth of colloidal binary solid-solution crystals is presented. Using a comprehensive set of Metropolis Monte Carlo simulations, we probe the influence of colloid size, interaction strength, and interaction range on the segregation process. The results are interpreted in terms of a simple, but descriptive mechanistic model that allows us to connect to studies of binary segregation in atomic systems. The validity of Metropolis Monte Carlo simulations for the nonequilibrium phenomena investigated in this work is established theoretically and by connections to Brownian dynamics and molecular dynamics simulations. It is demonstrated that standard Metropolis Monte Carlo, properly applied, can provide an efficient framework for studying many aspects of crystallization in colloidal systems. PMID- 20572733 TI - Molecular dynamics simulation study of friction force and torque on a rough spherical particle. AB - Recent developments in techniques of micro- and nanofluidics have led to an increased interest in nanoscale hydrodynamics in confined geometries. In our previous study [S. C. Kohale and R. Khare, J. Chem. Phys. 129, 164706 (2008)], we analyzed the friction force experienced by a smooth spherical particle that is translating in a fluid confined between parallel plates. The magnitude of three effects--velocity slip at particle surface, the presence of confining surfaces, and the cooperative hydrodynamic interactions between periodic images of the moving particle--that determine the friction force was quantified in that work using molecular dynamics simulations. In this work, we have studied the motion of a rough spherical particle in a confined geometry. Specifically, the friction force experienced by a translating particle and the torque experienced by a rotating particle are studied using molecular dynamics simulations. Our results demonstrate that the surface roughness of the particle significantly reduces the slip at the particle surface, thus leading to higher values of the friction force and hence a better agreement with the continuum predictions. The particle size dependence of the friction force and the torque values is shown to be consistent with the expectations from the continuum theory. As was observed for the smooth sphere, the cooperative hydrodynamic interactions between the images of the sphere have a significant effect on the value of the friction force experienced by the translating sphere. On the other hand, the torque experienced by a spherical particle that is rotating at the channel center is insensitive to this effect. PMID- 20572735 TI - Two-dimensional wetting: the role of atomic steps on the nucleation of thin water films on BaF2(111) at ambient conditions. AB - The interaction of water with freshly cleaved BaF(2)(111) surfaces at ambient conditions (room temperature and under controlled humidity) has been studied using scanning force microscopy in different operation modes. The images strongly suggest a high surface diffusion of water molecules on the surface indicated by the accumulation of water at step edges forming two-dimensional bilayered structures. Steps running along the 110 crystallographic directions show a high degree of hydrophilicity, as evidenced by small step-film contact angles, while steps running along other directions exhibiting a higher degree of kinks surprisingly behave in a quite opposite way. Our results prove that morphological defects such as steps can be crucial in improving two-dimensional monolayer wetting and stabilization of multilayer grown on surfaces that show good lattice mismatch with hexagonal ice. PMID- 20572734 TI - Electroelastic coupling between membrane surface fluctuations and membrane embedded charges: continuum multidielectric treatment. AB - The coupling of electric fields and charges with membrane-water interfacial fluctuations affects membrane electroporation, ionic conductance, and voltage gating. A modified continuum model is introduced to study charge interaction with membrane-water interfacial fluctuations in multidielectric environments. By surrounding a point charge with a low dielectric sphere, the linear Poisson Boltzmann equation is directly solved by calculating the reaction field potential via a method that eliminates singularity contributions. This allows treatment of charges located at dielectric boundaries. Two complementary mechanisms governing charge-fluctuation interactions are considered: (1) electroelastic deformation (EED), treating the membrane as an elastic slab (smectic bilayer model), and (2) electrohydrophobic solvation (EHS), accounting for water penetration into the membrane's hydrophobic core. EED often leads to large membrane thickness perturbations, far larger than those consistent with elastic model descriptions [M. B. Partenskii, G. V. Miloshevsky, and P. C. Jordan, Isr. J. Chem. 47, 385 (2007)]. We argue that a switch from EED to EHS can be energetically advantageous at intermediate perturbation amplitudes. Both perturbation mechanisms are simulated by introducing adjustable shapes optimized by the kinetic Monte Carlo reaction path following approach [G. V. Miloshevsky and P. C. Jordan, J. Chem. Phys. 122, 214901 (2005)]. The resulting energy profiles agree with those of recent atomistic molecular dynamics studies on translating a charged residue across a lipid bilayer [S. Dorairaj and T. W. Allen, Proc. Natl. Acad. Sci. U.S.A. 104, 4943 (2007)]. PMID- 20572736 TI - String-fluid transition in systems with aligned anisotropic interactions. AB - Systems with aligned anisotropic interactions between particles exhibit numerous phase transitions. A remarkable example of the fluid phase transition occurring in such systems is the formation of particle strings--the so-called "string" or "chain" fluids. We employ an approach based on the Ornstein-Zernike (OZ) equation, which allows us to calculate structural properties of fluids with aligned anisotropic interactions. We show that the string-fluid transition can be associated with the bifurcation of the "isotropic" correlation length into two distinct scales which characterize the longitudinal and transverse order in string fluids and, hence, may be used as a fingerprint of this transition. The comparison of the proposed OZ theory with the Monte Carlo simulations reveals fairly good agreement. PMID- 20572737 TI - Metallization of the C60/Rh(100) interface revealed by valence photoelectron spectroscopy and density functional theory calculations. AB - The electronic structure of single and multiple layers of C(60) molecules deposited on a Rh(100) surface is investigated by means of valence photoemission spectroscopy and density functional theory calculations. The binding of the fullerene monolayer to the metal surface yields the appearance of a new state in the valence band spectrum crossing the Fermi level. Insight into the metallization of the metal/fullerene interface is provided by the calculated electronic structure that allows us to correlate the measured interface state with a strong hybridization between the Rh metal states and the highest and lowest molecular orbitals. This results in a net charge transfer of approximately 0.5e-0.6e from the metal to the p states of the interfacial C atoms. The charge transfer is shown to be very short range, involving only the C atoms bound to the metal. The electronic structure of the second C(60) layer is already insulating and resembles the one measured for C(60) multilayers supported by the same substrate or calculated for fullerenes isolated in vacuum. The discussion of the results in the context of other C(60)/metal systems highlights the distinctive electronic properties of the molecule/metal interface determined by the Rh support. PMID- 20572738 TI - Narrow-escape times for diffusion in microdomains with a particle-surface affinity: mean-field results. AB - We analyze the mean time t(app) that a randomly moving particle spends in a bounded domain (sphere) before it escapes through a small window in the domain's boundary. A particle is assumed to diffuse freely in the bulk until it approaches the surface of the domain where it becomes weakly adsorbed, and then wanders diffusively along the boundary for a random time until it desorbs back to the bulk, etc. Using a mean-field approximation, we define t(app) analytically as a function of the bulk and surface diffusion coefficients, the mean time it spends in the bulk between two consecutive arrivals to the surface and the mean time it wanders on the surface within a single round of the surface diffusion. PMID- 20572739 TI - A refined hydrogen bond potential for flexible protein models. AB - One of the major disadvantages of coarse-grained hydrogen bond potentials, for their use in protein folding simulations, is the appearance of abnormal structures when these potentials are used in flexible chain models, and no other geometrical restrictions or energetic contributions are defined into the system. We have efficiently overcome this problem, for chains of adequate size in a relevant temperature range, with a refined coarse-grained hydrogen bond potential. With it, we have been able to obtain nativelike alpha-helices and beta sheets in peptidic systems, and successfully reproduced the competition between the populations of these secondary structure elements by the effect of temperature and concentration changes. In this manuscript we detail the design of the interaction potential and thoroughly examine its applicability in energetic and structural terms, considering factors such as chain length, concentration, and temperature. PMID- 20572740 TI - A demonstration of the inhomogeneity of the local dielectric response of proteins by molecular dynamics simulations. AB - The dielectric properties of proteins are important in determining responses to changes in pH, responses to external electric fields, and the energy associated with charge injection or charge transfer. Although the importance of electrostatic interactions in proteins is well established and they are routinely included in simulations, the dielectric properties of proteins are less frequently discussed. We use a combination of atomistic molecular dynamics simulation and continuum electrostatics models to calculate the local dielectric constant within regions of the model protein hen egg white lysozyme. The local dielectric response of the protein was found to be highly inhomogeneous and strongly dependent on the local chemical environment. In light of these findings, we discuss the use of models using a single effective dielectric constant for the whole protein and the relationship between variations in local protein dielectric response and the activity of protein sites. PMID- 20572742 TI - Force induced melting of the constrained DNA. AB - We develop a simple model to study the effects of the applied force on the melting of a double stranded DNA (dsDNA). Using this model, we could study the stretching, unzipping, rupture and slippagelike transition in a dsDNA. We show that in absence of an applied force, the melting temperature and the melting profile of dsDNA strongly depend on the constrained imposed on the ends of dsDNA. The nature of the phase boundary of the force-temperature diagram, which separates the zipped and the open state for the shearinglike transition is remarkably different than the DNA unzipping. PMID- 20572741 TI - Computing the conformational entropy for RNA folds. AB - We develop a polymer physics-based method to compute the conformational entropy for RNA tertiary folds, namely, conformations consisting of multiple helices connected through (cross-linked) loops. The theory is based on a virtual bond conformational model for the nucleotide chain. A key issue in the calculation of the entropy is how to treat the excluded volume interactions. The weak excluded volume interference between the different loops leads to the decomposition of the whole structure into a number of three-body building blocks, each consisting of a loop and two helices connected to the two ends of the loop. The simple construct of the three-body system allows an accurate computation for the conformational entropy for each building block. The assembly of the building blocks gives the entropy of the whole structure. This approach enables treatment of molten globule like folds (partially unfolded tertiary structures) for RNAs. Extensive tests against experiments and exact computer enumerations indicate that the method can give accurate results for the entropy. The method developed here provides a solid first step toward a systematic development of a theory for the entropy and free energy landscape for complex tertiary folds for RNAs and proteins. PMID- 20572743 TI - Extreme temperature episodes and mortality in Yakutsk, East Siberia. AB - INTRODUCTION: Although the health impacts of heat waves and, to a lesser extent, cold spells in big cities in moderate climates have been well documented, little is known about the same impacts in the circumpolar region. An epidemiological study in an Arctic town presents considerable difficulties for the statistician because of small population sizes. When daily mortality counts are mostly 0, 1 or 2, they are not normally distributed and do not fit the independence assumption. The aim of this study was to take these difficulties into account and assess the impacts of extreme temperature events on mortality rates in Yakutsk, a city with a strongly continental climate, situated near the north pole. METHOD: Long-term distributions of daily mean temperatures were analyzed for identification of heat waves and cold spells during the study period of 1999 to 2007. The authors investigated daily mortality from all non-accidental causes, coronary heart disease and cerebrovascular causes among the age groups 30-64 years and 65 years and over. Statistical analysis was in two steps. Step 1 involved Student's t tests of samples, which consisted of cumulative mortalities during each heat wave. This provided a measure of the average health effect of all identified heat waves, and the same analysis was performed separately for cold spells. At Step 2, the authors compared the observed cumulative mortality during each individual temperature wave with expected seasonal mortality, using chi(2) tests. RESULTS: The analysis of the impacts of six heat waves and three cold spells provided sufficient evidence that cardiovascular and non-accidental mortalities increased in Yakutsk during both heat waves and cold spells. The magnitude of established health effects was approximately the same for heat and cold. No significant differences were found between the two analyzed age groups in terms of relative excess mortality. Coronary heart disease mortality increased more than two-fold during some of the identified temperature waves, while non-accidental mortality increased by approximately 50%. The time lags between the temperature wave and observed increase in mortality varied between 8 and 14 days, which indicated that the health effects of temperature extremes were delayed rather than immediate. The evidence obtained of the effects of temperature waves on cerebrovascular mortality was not conclusive. Addressing the methodological implications of dealing with small cities, the authors linked the sensitivity of the applied statistical tests to arithmetic means and relative standard deviations of daily death counts, and to the duration of temperature waves. CONCLUSIONS: The proposed methodology can be applied in other medium-sized towns (populations >200,000, approximately); however, only large relative increases in mortality will be statistically significant. For example, relative risks of less than 2.0 for coronary disease mortality and 1.4 for non-accidental mortality are likely to be non-significant. PMID- 20572744 TI - Obesity, energy intake and physical activity in rural and urban New Zealand children. AB - INTRODUCTION: Concerns have been raised about childhood obesity and its long-term impact on the health of children. The objective of this study was to investigate rural-urban differences in body composition, energy intake, physical activity and screen time in New Zealand children. METHODS: This study reports on data collected in a large national cross-sectional population survey of 5-15 year-old New Zealanders (the 2002 National Children's Nutrition Survey, CNS02). Schools were randomly selected to participate, as were pupils from the selected schools. Measurements of body composition were taken at school. Energy intake, physical activity and screen time information were taken from interviews and questionnaires undertaken by the child and parent/guardian. Means and standard deviations were calculated in the Statistical Analysis System (SAS Inst; Cary, NC, USA). Differences between groups were analysed using Proc Mixed after adjusting for socio-economic status and ethnicity. Data indicating differences between groups were presented as least square means +/- 95% confidence limits (CL); unless otherwise stated, and the alpha was set at p< 0.05. RESULTS: Rural children had a significantly lower BMI, smaller waist circumferences and thinner skinfold measurements than urban children. The differences in skinfold thicknesses remained after controlling for ethnicity and socioeconomic status. Furthermore, urban boys were 1.3 times more likely to be overweight or obese than rural boys (95% confidence limits 1.1-1.6, p <0.01) and urban girls were 1.4 times more likely to be overweight or obese than rural girls (95% CL 1.2-1.7, p <0.01).There was no significant difference in the energy intake per day of rural and urban children. Similarly, there was no significant difference in the frequency of bouts of physical activity undertaken by rural and urban children. CONCLUSION: Differences were found in body composition with rural children being leaner than urban children. This finding is different from other Western countries and may be due to differences in the physical and social environment in New Zealand. More research is required to understand these potential environmental rural-urban differences. PMID- 20572745 TI - Mental health support in northern communities: reviewing issues on isolated practice and secondary trauma. AB - CONTEXT: Communities in northern Canada face many mental health concerns related to isolation, historical and intergenerational trauma effects, and economic issues. Access to mental health services is problematic due to geographic, cultural and economic issues. Reduced mental health services have resulted in more responsibility and stress for the remaining formal mental health practitioners (including counsellors, psychologists, social workers and nurses) and on informal mental health support, such as lay counsellors, Elders, family members, and community-identified helpers. ISSUE: This review explores the unique conditions found in northern-based mental health support in on-going efforts to develop a practice model for mental health support in the North and to better understand the connection between isolated practice and secondary trauma. Practitioners who work in isolated settings are often removed from other professionals, training opportunities, clinical supervision, and family support, with this seclusion contributing to feelings of professional and personal isolation. Aspects of isolation as well as the requirements of empathic engagement with clients leave practitioners vulnerable to various constructs of secondary trauma. The unique challenges of northern practice may contribute to added risk of secondary trauma for formal and informal mental health practitioners. Secondary trauma is defined under the constructs of burn-out, compassion fatigue, secondary traumatic stress, and vicarious trauma. Although research on the contribution of secondary trauma to the high-turnover rate of professionals in the North is scarce, informal reports suggest that northern practice may be detrimental to longevity in the field for mental health practitioners, especially those who come from outside northern communities. LESSONS LEARNED: The reviewed literature presents the unique challenges of formal (professional) and informal (para-professional and other) mental health practice in northern communities including: isolation related to the principle of confidentiality, geography, and lack of supervision; high visibility and lack of anonymity; and the struggle of negotiating membership in a community with professional and para-professional practice. The literature indicates that practitioners are challenged and effected by the work they do, including both negative and positive aspects. Professional and physical isolation are key areas to consider in the development of a practice model for northern mental health providers and in gaining a better understanding of the impact of isolation on the phenomenon of secondary trauma. Differing views and definitions on the phenomenon of secondary trauma continue to be espoused. The specific context of northern mental health support needs to be considered when practitioners use various construct labels to describe what is happening to them. As suggested by the literature, an understanding of northern cultures is essential for competent practice in such settings. This understanding includes the diversity of culture and also work and economic factors influence on the social psychology of communities and the resulting impact on mental health supporters. It is proposed that a conceptual and practice model be developed specifically for isolated mental health support in the North, and broadened to include informal mental health providers as well as formal practitioners. PMID- 20572747 TI - Meeting the needs of Nunavut families: a community-based midwifery education program. AB - CONTEXT: Pregnant Nunavut women are usually expected to relocate to distant and larger urban centres, often for several weeks, to give birth. A national study revealed that these women are less likely to have necessary information on pregnancy related topics and less satisfied with their maternity experiences. While prenatal and postpartum care can be accessed through nursing stations, opportunities for intrapartum care within Nunavut are limited to the hospital in Iqaluit or the birthing centre in Rankin Inlet. ISSUES: One strategy that may be help ameliorate these regional differences is increasing the integration of midwifery services. Many historical and political factors have contributed to the loss of traditional maternity care among the Inuit of Nunavut. A unique, multi layered midwifery education program, with a range of exit points from maternity care worker to baccalaureate degree, was implemented by a partnership between the Government of Nunavut and Nunavut Arctic College (NAC). Creative approaches were invoked to develop a program that is both culturally safe and ensures that graduates at midwifery diploma level are eligible to write the Canadian Midwifery Regulatory Exam (CMRE). The loss of traditional midwifery and the very dispersed population created challenges with respect to development of appropriate clinical learning sites where students can learn midwifery from midwives. Because NAC does not grant degrees, a collaborative partnership with Laurentian University is underway to meet the needs of those midwifery students who wish to complete a degree. LESSONS LEARNED: Midwifery has a bright future in Nunavut. Two students have already passed CMREs on their first attempt. Plans are in place to enroll a class in Cambridge Bay in the fall of 2010. One NAC student is enrolled in courses at Laurentian University and should complete the third year of that program in 2010. PMID- 20572746 TI - Biomonitoring in Greenland: human biomarkers of exposure and effects - a short review. AB - CONTEXT: Since 1997 the Arctic Monitoring and Assessment Programme (AMAP) has produced integrated assessment reports on the status of and trends in environmental persistent organic pollutants (POPs) in the Arctic ecosystem. Three reports on biomonitoring POPs and their health risks for Arctic populations were published in 1998, 2002, and 2009. ISSUE: The present review summarizes data from Greenland on human monitoring of biomarkers of POP exposure and bioaccumulation and the determination of biomarkers for POP effects. The review focuses on hormone disruptive potentials and some genetic sensitivity biomarkers. The overview covers Greenlandic studies from 2000 to 2006. LESSONS LEARNED: The Greenland biomonitoring studies showed general geographical and gender differences of bioaccumulated serum POP levels, which were primarily related to diet and lifestyle. A high intake of traditional Greenlandic diet (eg seal, whale, polar bear, and seabirds) together with smoking caused higher blood concentrations of POPs. The highest POP values were found on the east coast of Greenland. The receptor effect studies showed a general inverse relationship between high serum POP concentration and estrogen receptor (ER) and Ah-receptor (AhR) transactivity; in addition for men in the two West Greenlandic districts, Nuuk and Sisimiut, a trend towards increased induced AR activity was found. An observed trend to an opposite direction between the dioxin-like AhR and ER activity supports the perception of that dioxins exert an antiestrogen effect. In conclusion, the actual mixtures of serum POPs in Greenlandic Inuit have an endocrine disrupting potential. Comparisons between European and Greenlandic male serum POP levels showed significantly higher levels in Inuit; however, in the same study Inuit had significantly lower sperm DNA damage. Further studies are required to elucidate whether the serum POP related effects on hormone receptors and/or AhR are explanatory factors. 'The Arctic dilemma' is that along with the intake of the Greenlandic traditional diet that contains POPs, there are also a number of important nutrients, such as trace elements/antioxidants and marine unsaturated fatty acids which have favorable effects on health. However, a number of studies suggest that an increase in Western food items in the diet can lead to other health risks, such as the metabolic syndrome and its sequels increase in weight, hypertension, diabetes type 2, cardiovascular disease, and cancer, including breast cancer. To elucidate these aspects further studies are required, including those into biomarkers for exposure and effects, epigenetic contexts and the determination of relevant genetic polymorphisms, case-control as well as generation studies. Finally, there is a need for the development of new biomarkers to study the potential POP effects that inhibit the immune system and affect the development of the central nervous system. PMID- 20572748 TI - Postgraduate training at the ends of the earth - a way to retain physicians? AB - INTRODUCTION: The recruitment and retention of health workers, crucial to health service delivery, is a major challenge in many rural and remote areas. Finnmark, the most remote and northern county in Norway, has faced recurrent shortages during the last 5 decades, especially of primary care physicians. METHODS: This article describes a postgraduate training model for family physicians and public health/community medicine physicians, based on group tutorial and in-service training in rural areas. The effect of the training programs on physician retention in Finnmark is evaluated by a longitudinal cohort study. RESULTS: In total, 65-67% of the physicians from the programs are still working in the county 5 years after completion of the group tutorial. Rural practice provides good learning conditions when accompanied by appropriate tutelage, and in-service training allows the trainees and their families to 'grow roots' in the remote area while in training. The group tutorial develops peer support and professional networks to alleviate professional isolation. CONCLUSION: On the basis of these findings, traditional centralistic training models are challenged. Postgraduate (vocational) training (residency) for primary care physicians can be successfully carried out in-service in remote areas, in a manner that enhances retention without compromising the quality of the training. PMID- 20572749 TI - Internship at the ends of the earth - a way to recruit physicians? AB - CONTEXT: The recruitment of sufficient health workers in rural and remote areas has been a constant challenge in many countries for decades. This article describes how medical internship (18 months of mandatory practical training, including 6 months in primary care, after graduation but before granted full license as a doctor) is used in Norway as one method of recruiting young doctors. Finnmark, the most northern and remote county, offers the most challenging medical practice and is also the area most dependent on interns as medical workforce, and later as licensed doctors. ISSUE: Providing adequate professional and social support for the interns during this challenging service is regarded as a prerequisite to retaining them for further service after internship. To accomplish this, a special tutorial program has been implemented since 1997. The scope of this study is to examine whether internship in Finnmark, accompanied by the group tutelage, enhances recruitment and, if so, what are the main predictors for taking their first voluntary job in the north. LESSONS LEARNED: Twice as many interns as were expected from their background chose their first job in the north. Those brought up in the region and the graduates from the (northern) University of Tromso, were most likely to make this choice. However, graduates from Oslo were also much more likely to choose a job in the north after internship in Finnmark than had been predicted in their last term in medical school. Internship in Finnmark also increased the probability of choosing primary care, which is a political priority in Norway. This indicates that internship in remote areas, given the appropriate professional and social support, contributes to improved recruitment of doctors to underserved areas. PMID- 20572750 TI - Development of a physiotherapy prioritization tool in the Baffin Region of Nunavut: a remote, under-serviced area in the Canadian Arctic. AB - CONTEXT: This article describes the development and evaluation of a tool to prioritize physiotherapy referrals in a remote, under-serviced region in Canada's eastern Arctic. The Baffin Region of Nunavut is home to approximately 16 000 people dispersed across 12 communities accessible only by air. Physiotherapists are based out of the capital city, but provide services to clients throughout the region. Physiotherapists in the Baffin Region are generalists, treating clients from across the lifespan and from all practice areas. The region is under serviced with regard to physiotherapy, and long waitlists for service are maintained. No previous physiotherapy prioritization tool existed to manage the diverse caseload. ISSUE: Physiotherapists were dissatisfied with perceived inequities in service delivery among the different communities in the region, and between client types. In response, a tool was created to prioritize physiotherapy referrals based on urgency and need, regardless of client location. The prioritization tool was developed by combining the authors' knowledge of the distinct and unique characteristics of the Baffin Region with background research. Three methods were used to collect background information: (1) a literature search; (2) a review of prioritization policies from other regions; and (3) interviews with physiotherapists working in similar remote areas in Canada. From the background research, common characteristics in prioritizing physiotherapy referrals as 'high priority' emerged. These were combined with the identified characteristics of the Baffin Region to create a tool that could prioritize physiotherapy referrals from multiple client types. The prioritization tool was then implemented and evaluated over a four-month period. LESSONS LEARNED: Following the implementation of the prioritization tool, a greater percentage of scheduled physiotherapy appointments were devoted to high priority groups, and there was a greater amount of service delivered to clients from the remote communities. Physiotherapists subjectively reported improved job satisfaction knowing that clients over the entire region were being assessed in order of priority, and decreased job stress as a result of reduced therapist time spent triaging referrals. Unanticipated outcomes from using the prioritization tool included subjectively reported improved communication with other health professionals, and changes in physiotherapy service delivery methods in the Baffin Region. Using the prioritization tool prompted increased client travel to the capital city for urgent physiotherapy appointments, increased use of videoconferencing for follow-up physiotherapy appointments, and increased use of a consultative model to deliver physiotherapy services. The tool could be adapted for use by other rural or remote physiotherapists working with multiple client populations in under-serviced areas. The Baffin Region Physiotherapy Prioritization Tool provides an objective method for making triage decisions, and has improved the equity with which physiotherapy services are delivered across the region. PMID- 20572751 TI - The trans-septal approach to the orbital apex via the contralateral exenterated orbit. AB - PURPOSE: To report a unique approach to the orbital apex through the contralateral orbit. METHODS: A 65-year-old male presented with right compressive optic neuropathy due to nasopharyngeal carcinoma spread. Clinical evaluation and imaging showed a right orbital apex mass. Surgery included apical orbital tumor debulking, and orbital decompression performed via the contralateral exenterated side. Postoperatively, symptoms were relieved. CONCLUSIONS: Orbitotomy via the contralateral exenterated orbit should be considered as a surgical option in these unique patients requiring direct access to the orbital apex. PMID- 20572752 TI - Systemic absorption of Tc-99m-pertechnetate during dacryoscintigraphy: a note of caution. AB - We report a 37-year-old patient with the history of bilateral epiphora, who was referred to our department for dacryoscintigraphy imaging. The patient had bilateral obstruction of the lacrimal apparatus at the sac-duct level on the scintigraphy images. Delayed imaging showed Tc-99m pertechnetate uptake in the thyroid due to systemic absorption of the tracer from the conjunctiva. We recommend using tracers with large particle size and lower possibility of mucosal absorption for dacryoscintigraphy in order to decrease unnecessary thyroid radiation. PMID- 20572753 TI - A challenging case of primary orbital mesenchymal chondrosarcoma. AB - Mesenchymal chondrosarcoma is an uncommon lesion of the bone and extraskeletal tissue involving very rarely the orbit. Histopathological features of this lesion include: undifferentiated mesenchymal cells with islands of mature hyaline cartilage. We present a case of a 23-year-old man with primary orbital mesenchymal chondrosarcoma (OMC) with an uncommon management. This anecdotic report could be a contribution to the understanding of this unusual tumor. PMID- 20572754 TI - Centurion syndrome. PMID- 20572755 TI - Myeloma-associated orbital amyloidosis. AB - Orbital amyloidosis is extremely rare and may be localized finding or secondary to a systematic process. The majority of the patients with orbital amyloidosis have primary localized disease. We report a 55 year old male with multiple myeloma and secondary amyloidosis who presented with incidental bilateral orbital masses on MRI. Biopsy revealed amyloid deposition. We review the previously published cases of the orbital amyloidosis secondary to systematic light chain (AL) amyloidosis, including one patient with multiple myeloma. The clinical signs and symptoms, histopathologic findings, and radiographic features of orbital amyloidosis are discussed. PMID- 20572756 TI - Radiolabeling and dose fixation study of oral alpha-ketoglutarate as a cyanide antidote in healthy human volunteers. AB - CONTEXT: Radiolabeling and dose fixation study of alpha-ketoglutarate (A-KG). OBJECTIVE: A-KG is a potential oral antidote for cyanide poisoning. Its protective efficacy in animals was best exhibited at a dose of 2.0 g/kg body weight, which when extrapolated to human is very high. The objective of this study was to reduce the dose of A-KG in humans with concomitant increase in its bioavailability, employing pharmacoscintigraphic techniques to assess kinetics in man. MATERIALS AND METHODS: A-KG was radiolabeled with technetium-99m pertechnetate (Tc-99m) and its purity, labeling efficiency, and stability in vitro were determined by instant thin layer chromatography. Time-dependent bio absorption of the drug in rats and rabbits was assessed by gamma scintigraphy after oral administration of a tracer dose of (99m)Tc-A-KG mixed with nonradioactive A-KG at a concentration of 0.1-2.0 g/kg in the presence or absence of aqueous dilution. Furthermore, scintigraphy and radiometry studies were performed in healthy human volunteers using 5-20 g of A-KG, given in single or split doses followed by different quantity of water. Drug bioavailability was estimated periodically. RESULTS: High radiolabeling (>97%) of A-KG with a stability of 24 h in vitro was obtained. Less than 1% absorption of the drug occurred within 20 min after A-KG was administered in animals at a concentration of 2.0 g/kg body weight. One-tenth reduction in dose increased the bioavailability to 15%. Significant improvement in gastric emptying of the drug was achieved when the drug was administered along with 1-5 mL of water. In humans, two doses of 10 g A-KG given at an interval of 10 min, followed by 300 mL of water, increased the drug bioavailability to 40% as compared to a single dose of 20 g. DISCUSSION: Significant reduction in A-KG dose was achieved in humans as compared to the recommended dose in animals. CONCLUSION: Aqueous dilution improves the bioavailability of A-KG in humans. PMID- 20572757 TI - Acute intentional toxicity: endosulfan and other organochlorines. AB - INTRODUCTION: Organochlorine pesticides continue to be used in several developing countries despite concerns regarding their toxicity profile. Endosulfan is an organochlorine recognized as an important agent of acute toxicity. METHODS: In this retrospective study, the clinical features, course, and outcomes among patients with acute endosulfan poisoning requiring admission to the hospital during an 8-year period (1999-2007) were reviewed. RESULTS: Among 34 patients hospitalized during this study period for alleged organochlorine poisoning, 16 patients with endosulfan poisoning were identified. The majority (75%) received initial treatment at a primary or secondary center. Neurological toxicity predominated, particularly low sensorium (81%) and generalized seizures (75%), including status epilepticus (33%). Other features observed included hepatic transaminase elevation, azotemia, metabolic acidosis, and leukocytosis. Mechanical ventilation was required in 69% and vasoactive agents in 19%. In hospital mortality was 19%. There were no gross neurological sequelae at discharge. In three other patients who presented with organochlorine poisoning, the compounds ingested were lindane, endrin, and dicofol (n = 1 each). The course and outcomes in these patients were unremarkable and all three patients survived. CONCLUSIONS: Endosulfan is capable of high lethality and significant morbidity. The commonest manifestations are neurological although other organ dysfunction also occurs. In the absence of effective antidotes, restriction of its availability, along with prompt treatment of toxicity, including preemptive anticonvulsant therapy are suggested. PMID- 20572758 TI - Airborne spread of Pneumocystis jirovecii. PMID- 20572759 TI - Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. AB - BACKGROUND: Airborne transmission of Pneumocystis has been demonstrated in animal models and is highly probable in humans. However, information concerning burdens of Pneumocystis jirovecii (human-derived Pneumocystis) in exhaled air from infected patients is lacking. Our objective is to evaluate P. jirovecii air diffusion in patients with Pneumocystis pneumonia. METHODS: Patients admitted with Pneumocystis pneumonia were prospectively enrolled from 9 January 2008 to 21 July 2009. Air samples (1.5 m(3)) were collected on liquid medium with a commercial sampler at 1-, 3-, 5-, and 8-m distances from patients' heads. Air control samples were collected away from Pneumocystis pneumonia patient wards and outdoors. Samples were examined for P. jirovecii detection and quantification using a real-time polymerase chain reaction assay targeting the mitochondrial large subunit ribosomal RNA gene. RESULTS: Forty patients were diagnosed as having Pneumocystis pneumonia. Air sampling was performed in the environment for 19 of them. At a 1-m distance from patients' heads, P. jirovecii DNA was detected in 15 (79.8%) of 19 patients, with fungal burdens ranging from 7.5 X 103 to 4.5 X 106 gene copies/m(3). These levels decreased with distance from the patients (P < .002). Nevertheless, 4 (33.3%) of the 12 samples taken at 8 m, in the corridor adjacent to their room, were still positive. Forty control samples were collected and remained negative. CONCLUSION: This study provides the first quantitative data on the spread of P. jirovecii in exhaled air from infected patients. It sustains the risk of P. jirovecii direct transmission in close contact with patients with Pneumocystis pneumonia and leads the way for initiating a quantitative risk assessment for airborne transmission of P. jirovecii. PMID- 20572760 TI - Evaluation of plasma human herpesvirus 8 DNA as a marker of clinical outcomes during antiretroviral therapy for AIDS-related Kaposi sarcoma in Zimbabwe. AB - BACKGROUND: The usefulness of plasma human herpesvirus 8 (HHV-8) DNA as a marker of response to treatment for acquired immunodeficiency syndrome-associated Kaposi sarcoma (AIDS-KS) in an African setting is unknown. METHODS: We conducted a prospective pilot study at the Parirenyatwa Hospital Kaposi Sarcoma Clinic (Harare, Zimbabwe) to investigate the hypothesis that the clinical response of AIDS-KS is associated with suppression of HHV-8 DNA. Antiretroviral therapy (ART) was provided as coformulation of abacavir, lamivudine, and zidovudine. Clinical response was defined as survival to week 96 with either complete or partial resolution of KS disease. RESULTS: Ninety ART-naive participants (62 men and 28 women) aged >18 years who had human immunodeficiency virus type 1 (HIV-1) infection and biopsy-confirmed KS were studied; 82% had stage T1 disease. Fifty participants received adjunctive chemotherapy. The median CD4(+) lymphocyte count increased from 124 cells/microL at baseline to 281 cells/microL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log(10) copies/mL, the plasma HHV-8 DNA level decreased from 660 to <25 copies/mL, and HHV-8 DNA level in peripheral blood mononuclear cells decreased from 2790 to 37 copies/10(6) cells (P < .001 for each comparison). There were 14 deaths (16%) and 13 patients (15%) lost to follow-up. The most common cause of death was infection. Clinical response of KS occurred in 17 participants (19%). Pretreatment plasma HHV-8 DNA levels of <660 copies/mL were associated with greater survival (odds ratio, 2.83; 95% confidence interval, 1.07-7.53; P = .04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; P = .006). CONCLUSIONS: AIDS-KS tumor responses after ART initiation were limited. Pretreatment plasma HHV-8 DNA level may be a surrogate for KS disease that is in need of intensive clinical management. PMID- 20572761 TI - The two faces of hepatitis E virus. AB - Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%-21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration-approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world. PMID- 20572762 TI - Preventing catheter-related bloodstream infections outside the intensive care unit: expanding prevention to new settings. AB - With the growing recognition of the preventability of catheter-related bloodstream infections (CRBSIs), reducing the number of CRBSIs acquired in health care facilities has become an important patient safety goal. To date, most prevention efforts have been conducted in intensive care units (ICUs); however, many central venous catheters (CVCs) are found outside the ICU, and rates of catheter-associated bloodstream infections in these settings appear to be similar to rates of these infections in ICUs. CVCs are also used in patients who primarily receive their care as outpatients, including those requiring hemodialysis, undergoing treatment for malignancies, and receiving parenteral nutrition. In some of these patients, CVCs might be used for extended periods, prolonging the patient's time at risk for CRBSIs and highlighting the potential need to look beyond insertion-based interventions to prevent infections. To meet the goal of reducing the number of all CRBSIs associated with health care, further attention on CRBSIs occurring outside the ICU is needed; however, this effort will require a better understanding of the epidemiology and prevention of these infections. PMID- 20572763 TI - Escherichia coli sequence type ST131 as the major cause of serious multidrug resistant E. coli infections in the United States. AB - BACKGROUND: Escherichia coli sequence type ST131 (O25:H4), associated with the CTX-M-15 extended-spectrum beta-lactamase, has emerged internationally as a multidrug-resistant pathogen but has received little attention in the United States. METHODS: From the SENTRY and Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance programs, 127 E. coli clinical isolates from hospitalized patients across the United States in 2007, stratified by extended-spectrum cephalosporin and fluoroquinolone phenotype and bla(CTX-M 15) genotype, were assessed for phylogenetic group, ST131 status, susceptibility profile, virulence genotype, gyrA and parC sequence, and pulsed-field gel electrophoresis profile. RESULTS: The 54 identified ST131 isolates (all fluoroquinolone resistant) accounted for an estimated 17% of the source populations, including 67%-69% of isolates resistant to extended-spectrum cephalosporins or fluoroquinolones, 55% of those resistant to both fluoroquinolones and trimethoprim-sulfamethoxazole, and 52% of multidrug resistant isolates. Their distinctive virulence profiles were more extensive compared with other antimicrobial-resistant isolates but similarly extensive compared with antimicrobial-susceptible isolates. Pulsed-field profiling suggested ongoing dissemination among locales, with concentration of bla(CTX-M 15) within specific ST131 lineages. A historical ST131 isolate lacked the 2007 ST131 isolates' conserved fluoroquinolone resistance-associated single-nucleotide polymorphisms in gyrA and parC. CONCLUSIONS: A single E. coli clonal group, ST131, probably caused the most significantly antimicrobial-resistant E. coli infections in the United States in 2007, thereby constituting an important new public health threat. Enhanced virulence and/or antimicrobial resistance compared with other E. coli, plus ongoing dissemination among locales, may underlie ST131's success. Urgent investigation of the sources and transmission pathways of ST131 is needed to inform mitigation efforts. PMID- 20572764 TI - Prophylactic vaccination against periodontal disease: a systematic review of preclinical studies. AB - BACKGROUND: Periodontal vaccine against periodontopathic bacteria has been tested in various animal models, such as in non-human primates and murine species. The aim of this preliminary study is to systematically review all preclinical (i.e., animal) studies that present supporting evidence for the feasibility of formulating a prophylactic human periodontal vaccine. METHODS: A manual and electronic literature search was made for animal studies up to February 2010 that presented clinical, morphologic (alveolar bone level), and immunologic data for the efficacy of a prophylactic periodontal vaccine. A systematic approach was followed by two independent reviewers and included eligibility criteria for study inclusion, quality assessment, determination of outcome measures, screening method, data extraction, data synthesis, and drawing of conclusions. RESULTS: Only two randomized controlled animal trials qualified, and they reported exactly opposite effects of vaccine administration in Macaca fascicularis experimental periodontitis models by administration of two different agents (i.e., a negative effect with combined whole-cell antigens of Porphyromonas gingivalis and Prevotella intermedia in contrast to a positive effect with cysteine proteases of P. gingivalis). However, no statistical process could be applied to their results (data inadequately reported) in order to pool and evaluate the changes in outcome measures after vaccine administration, which, highlighted their mediocre study quality. CONCLUSIONS: Because of the insufficient quantity and quality of animal trials, no adequate evidence could be gathered to use the beneficial effects of these animal experiments to formulate a prophylactic human periodontal vaccine. Thus, good-quality animal trials are needed in this field of vaccine testing. PMID- 20572765 TI - Effects of irrigation with an antiseptic and oral administration of azithromycin on bacteremia caused by scaling and root planing. AB - BACKGROUND: Transient bacteremia frequently occur secondary to several periodontal procedures. The purpose of the present study is to investigate the effects of irrigation with an essential oil-containing antiseptic (EO) and oral administration of azithromycin (AZM) on bacteremia caused by scaling and root planing (SRP). METHODS: Thirty patients with chronic periodontitis were randomly assigned to three groups (control, EO, and AZM). The EO group received quadrant subgingival irrigation with EO, and mouthrinsing was continued at home for 1 week. Oral administration of AZM was started 3 days before SRP in the AZM group. No adjunctive treatment was performed before SRP in the control group. Peripheral blood and subgingival plaque were collected at baseline and after 1 week. The second blood sample was taken 6 minutes after the initiation of quadrant SRP. The blood samples were cultured and analyzed for bacteremia. Quantitative analysis of periodontopathic bacteria in the sulcus was performed using the polymerase chain reaction Invader method. RESULTS: Bacteremia incidence rates were 90%, 70%, and 20% for the control, EO, and AZM groups, respectively. Significant reduction of the incidence of bacteremia was shown in the AZM group only (P <0.01). Subgingival bacterial counts significantly decreased in both the EO and AZM groups (P <0.01). CONCLUSIONS: Quadrant SRP frequently induced bacteremia. Although AZM was effective in reducing bacteremia incidence, EO showed less effectiveness. PMID- 20572766 TI - Gingival RAGE expression in calorie-restricted versus ad libitum-fed rats. AB - BACKGROUND: The receptor for advanced glycation end products (RAGE) is a multiligand receptor expressed in a number of cell types, including gingival epithelia. RAGE mediates inflammation and induces cellular oxidative stress. Upregulation of RAGE is associated with various diseases, such as periodontal and cardiovascular diseases. This study examines the hypothesis that the gingiva of rats fed a calorie-restriction (CR) diet expresses lower levels of RAGE than the gingiva of rats fed an ad libitum (AL) diet. METHODS: Male F344BN rats (n = 16) from the National Institute on Aging (NIA) were fed a CR (n = 8) or AL (n = 8) diet according to NIA recommendations. Rats were sacrificed by guillotine at 8 (n = 5), 18 (n = 3), 29 (n = 4), and 38 (n = 4) months of age. The gingiva from around the molars was dissected and submitted for histologic and molecular analyses. RESULTS: Immunohistochemistry revealed that RAGE was expressed in the plasma membrane and cytoplasm of gingival epithelial cells and endothelial cells from both groups. RAGE mRNA levels were quantified relative to levels of GAPDH mRNA by real-time reverse-transcriptase polymerase chain reaction. The mean relative RAGE mRNA level in the CR group (7.26 +/- 0.54) was lower than in the AL group (10 +/- 1.4) (P <0.05). There were no detectable differences in RAGE expression according to animal age. CONCLUSION: Gingival RAGE expression in rats is reduced by calorie restriction. PMID- 20572767 TI - Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 Fatty acids and low-dose aspirin. AB - BACKGROUND: Host modulatory therapy has been proposed as a treatment for periodontal diseases. Omega-3 (omega-3) polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were shown to have therapeutic anti-inflammatory and protective actions in inflammatory diseases including periodontitis. The goal of this study was to test an innovative strategy for periodontal treatment in a clinical experiment. METHODS: Eighty healthy subjects (40 in each group) with advanced chronic periodontitis were enrolled in Mansoura, Egypt, in a parallel-design, double-masked clinical study. The control group was treated with scaling and root planing (SRP) and a placebo, whereas the omega-3 group was treated with SRP followed by dietary supplementation of fish oil (900 mg EPA + DHA) and 81 mg aspirin daily. Saliva samples were obtained from all patients at baseline and 3 and 6 months for evaluation of receptor activator of nuclear factor-kappa B ligand (RANKL) and matrix metalloproteinase-8 (MMP-8). Plaque and gingival indices, bleeding on probing, probing depths, and attachment levels were recorded at the same time points. RESULTS: Statistical analyses demonstrated a significant reduction in probing depths and a significant attachment gain after 3 and 6 months in the omega-3 group compared to baseline and the control group (P <0.05). Salivary RANKL and MMP-8 levels showed significant reductions in the omega-3 group in response to treatment at 3 and 6 months and compared to the control group at 6 months (P <0.01). Supplementation with omega-3 + aspirin resulted in a significant shift in the frequency of pockets with probing depths <4 mm (P <0.05). CONCLUSION: The results of this preliminary clinical study suggest that dietary supplementation with omega-3 PUFAs and 81 mg aspirin may provide a sustainable, low-cost intervention to augment periodontal therapy. PMID- 20572768 TI - Application of a motivation-behavioral skills protocol in gingival lichen planus: a short-term study. AB - BACKGROUND: The main objective of the present study was to assess the efficacy of a motivation-behavioral skills protocol for plaque control in patients with gingival lichen planus. METHODS: A pre- and post-test descriptive clinical study was made of 40 consecutive white patients with gingival lichen planus: five males (12.5%) and 35 females (87.5%); mean age: 57 years. A motivation-behavioral skills protocol for oral hygiene was applied, with the determination of gingival scores (gingival index, plaque extension, and Community Periodontal Index of Treatment Needs [CPITN]) and patient evaluation after 4 and 8 weeks. RESULTS: The clinical parameters in relation to the different forms of gingival lichen planus showed statistically significant improvements for gingival index, plaque extension, and CPITN (P <0.001) as determined 4 and 8 weeks after starting the program. CONCLUSIONS: The application of an active prevention program in patients with gingival lichen planus is important because it offers benefits for periodontal health. However, more long-term studies are needed to confirm the results obtained. PMID- 20572769 TI - How does neuroscience affect our conception of volition? AB - Although there is no clear concept of volition or the will, we do have intuitive ideas that characterize the will, agency, and voluntary behavior. Here I review results from a number of strands of neuroscientific research that bear upon our intuitive notions of the will. These neuroscientific results provide some insight into the neural circuits mediating behaviors that we identify as related to will and volition. Although some researchers contend that neuroscience will undermine our views about free will, to date no results have succeeded in fundamentally disrupting our common sense beliefs. Still, the picture emerging from neuroscience does raise new questions, and ultimately may put pressure on some intuitive notions about what is necessary for free will. PMID- 20572770 TI - Watching synaptogenesis in the adult brain. AB - Although the lifelong addition of new neurons to the olfactory bulb and dentate gyrus of mammalian brains is by now an accepted fact, the function of adult generated neurons still largely remains a mystery. The ability of new neurons to form synapses with preexisting neurons without disrupting circuit function is central to the hypothesized role of adult neurogenesis as a substrate for learning and memory. With the development of several new genetic labeling and imaging techniques, the study of synapse development and integration of these new neurons into mature circuits both in vitro and in vivo is rapidly advancing our insight into their structural plasticity. Investigators' observation of synaptogenesis occurring in the adult brain is beginning to shed light on the flexibility that adult neurogenesis offers to mature circuits and the potential contribution of the transient plasticity that new neurons provide toward circuit refinement and adaptation to changing environmental demands. PMID- 20572772 TI - The genomic, biochemical, and cellular responses of the retina in inherited photoreceptor degenerations and prospects for the treatment of these disorders. AB - The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Muller glia, microglia, and the retinal vasculature. Finally, we report on potential pharmacologic and biologic therapies, the critical role of histopathology as a prerequisite to treatment, and the exciting promise of gene therapy in animal models and in phase 1 trials in humans. PMID- 20572776 TI - Perceptions of audible nasal emission in speakers with cleft palate: a comparative study of listener judgments. AB - OBJECTIVE: Audible nasal emission is a common speech distortion observed in persons with cleft palate. This study examined the validity and reliability of perceptual judgments of audible nasal emission using interval scaling and magnitude estimation techniques. PARTICIPANTS: Speech samples were collected from six adolescents with repaired cleft palate, all of whom demonstrated audible nasal emission. A total of 31 adults performed rating tasks in which they judged the severity of audible nasal emission in speech samples. MEASURES: Occurrences of audible nasal emission in speech samples were identified using visual and auditory inspection. Using an acoustic modification technique, samples were digitally modified to amplify perceived occurrences of audible nasal emission to create three stimulus conditions. The original recording of the speech samples served as a control condition. The severity of audible nasal emission in the samples was judged by multiple listeners using interval scaling and magnitude estimation without a modulus. Statistical analysis included analysis of variance, regression, and curve-fitting methods. RESULTS: Magnitude-estimation ratings demonstrated stronger evidence of validity and reliability than interval scaling. A curvilinear relationship was found between the sets of ratings. CONCLUSIONS: The results of this study suggest that audible nasal emission may be a prothetic or ratio-level perceptual continua. Listeners should consider using magnitude estimation or other ratio-based methods for perceptual judgments of audible nasal emission. PMID- 20572771 TI - Category learning in the brain. AB - The ability to group items and events into functional categories is a fundamental characteristic of sophisticated thought. It is subserved by plasticity in many neural systems, including neocortical regions (sensory, prefrontal, parietal, and motor cortex), the medial temporal lobe, the basal ganglia, and midbrain dopaminergic systems. These systems interact during category learning. Corticostriatal loops may mediate recursive, bootstrapping interactions between fast reward-gated plasticity in the basal ganglia and slow reward-shaded plasticity in the cortex. This can provide a balance between acquisition of details of experiences and generalization across them. Interactions between the corticostriatal loops can integrate perceptual, response, and feedback-related aspects of the task and mediate the shift from novice to skilled performance. The basal ganglia and medial temporal lobe interact competitively or cooperatively, depending on the demands of the learning task. PMID- 20572777 TI - New clinical method for alveolar bone graft evaluation in cleft patients: a pilot study. AB - The objective of this analytical cross-sectional study was to develop and test a new clinical evaluation method, using two sets of clinical criteria: (1) probing depth for teeth at either side of the grafted region and (2) residual defect at the central faciolingual region of the alveolar bone graft site, for assessing alveolar bone graft outcomes in patients with cleft of the lip and palate. Thirteen patients, 8 to 13 years old, with cleft lip and palate who underwent alveolar bone graft at Srinagarind Hospital and Faculty of Dentistry of Khon Kaen University were recruited into the study to test the agreement between two sets of data: (1) clinical examination scores and an expert's clinical judgment, (2) clinical and radiographic examination scores (Bergland and Chelsea scales). Study results showed that between the two criteria used in the new clinical method, reliability of the first criterion was higher than that of the second, .66 to 1.00 and .59 to .65, respectively. The reliability test for radiographic evaluation showed that the Chelsea scale had higher agreement than the Bergland, .80 to 1.00 and .64 to .86, respectively. Sensitivity, specificity, and likelihood ratio of the three proposed methods could not be concluded statistically due to the small sample size. In conclusion, even though the study sample was small, the method offers useful prospects as a supplement, if not an alternative, to overcome identified deficiencies of the Bergland and Chelsea scales and computed tomography scans, which raise concerns about radiation hazards and costs. PMID- 20572778 TI - Clinical-anthropometric and aesthetic analysis of nose and lip in unilateral cleft lip and palate patients. AB - OBJECTIVE: Presentation of a technique to determine objectively the degree of symmetry in the area of nose and lip in cleft patients based on analysis of photographs. To compare the objective measurements with the subjective impression. DESIGN: This was a retrospective study using a predefined photo documentation standard to capture images of the area of nose and lip. SETTING: Department of Oral and Maxillofacial Surgery, University of Jena, Germany. PATIENTS: Unilateral cleft patients following primary lip repair (group 1; n = 36) or secondary correction (group 2; n = 23). MAIN OUTCOME MEASURES: Measurements were taken on standardized photographs of three dimensions in the area of the nose and two dimensions in the upper lip region. Sign tests were used to ascertain differences between the cleft and unaffected sides separately for each group. Subjective impressions regarding symmetry were gathered and quantified by means of a visual analog scale (VAS). The Mann-Whitney U test was employed to compare the observers' impressions between the two groups. RESULTS: While significant side differences were found for all distances in group 1, only the side differences in the height of the nostril remained significant in group 2. Subjective evaluation of the nostril area improved significantly following corrective surgery. However, no such change in the area of the upper lip was recognized by the observers. CONCLUSIONS: We were able to demonstrate that the measurable symmetry of the nostril area, as well as the upper lip, was significantly enhanced by corrective surgery. However, only the subjective impression of the nostril was improved. PMID- 20572779 TI - Ethnic variations in the estimated prevalence of orofacial clefts in Taiwan, 2004 to 2006. AB - BACKGROUND: Foreign-born mothers have been reported to have better pregnancy outcomes as measured by the preterm birth rate, neonatal mortality, and birth weight compared with native-born mothers in Belgium, France, Taiwan, and the United States. However, little is known about the association between maternal nationality and the prevalence of orofacial clefts in Asian countries. METHODS: Taiwan Birth Registry data from 2004 to 2006 were analyzed for an association between maternal nationality and orofacial clefts. Singleton live births with a gestational age >=24 weeks were included in this study. RESULTS: The overall estimated prevalence percentages of orofacial clefts were 0.11 (95% confidence interval [CI] = 0.03 to 0.12) among newborns of Taiwan-born mothers (TBMs) and 0.13 (95% CI = 0.04 to 0.16) among newborns of foreign-born mothers (FBMs), respectively. The estimated prevalence of orofacial clefts of all live births of FBMs in Taiwan was similar to that of the FBMs from Southeast Asian countries. CONCLUSION: There was a slightly higher but no significant difference of estimated prevalence of orofacial clefts between newborns of TBMs and newborns of FBMs in Taiwan. PMID- 20572780 TI - An epidemiologic study of orofacial clefts in Hamedan City, Iran: a 15-year study. AB - OBJECTIVE: To determine the epidemiology of cleft lip and/or palate (CL/P) in births in hospitals of Hamedan City, Iran, and to evaluate the etiologic factors that have a role in the development of these anomalies. DESIGN: This research was a 15-year cross-sectional study (1993 to 2008). PARTICIPANTS: All infants born with CL/P during the study period comprised the study group. One thousand healthy children without cleft anomalies born in the same hospitals during the study period comprised the control group. RESULTS: The prevalence of CL/P was 1.016 per 1000 live births (53.4% boys and 46.6% girls). Cleft lip associated with cleft palate (CLP) was the most common type of anomaly (53.5%), followed by isolated cleft lip (CL; 28.7%) and isolated cleft palate (CP; 17.8%). Eighty-six babies (81%) had unilateral CL and 20 babies (19%) had bilateral CL. Twenty-three newborns with CL/P (17.8%) had other congenital deformities. The frequency of CL/P in parents, siblings, and relatives of newborns in study group was higher than in the control group. There was a significant difference between the study and control groups with respect to maternal drug intake, trauma, smoking, and x ray exposure during pregnancy. CONCLUSION: The birth prevalence of CL/P in Hamedan City was closer to the prevalence of CL/P in the United States and Europe than Africa and the Far East. We found that the presence of cleft in parents, siblings, and other relatives; maternal drug intake; trauma; radiation; and smoking were risk factors for cleft development in newborns. PMID- 20572781 TI - Entacapone. AB - IMPORTANCE OF THE FIELD: Levodopa (LD) is an efficient drug for patients with Parkinson's disease (PD). Its short half-life supports peaks and troughs. These plasma fluctuations support alternating stimulation of striatal postsynaptic dopamine receptors and thus onset of motor complications. They are significant components for the quality of treatment of PD patients. AREAS COVERED IN THIS REVIEW: This review discusses peripheral components of motor complication manifestation related to LD metabolism. WHAT THE READER WILL GAIN: LD troughs are associated with wearing off, which is reappearance of motor symptoms with decreasing drug effect. The addition of the catechol-O-methyltransferase inhibitor entacapone (EN) to LD/carbidopa (CD) improves wearing off, as EN prolongs LD half-life and avoids troughs. LD peaks are mostly related to peak dose dyskinesia, which are involuntary movements due to a central overstimulation with dopamine. One time addition of EN to LD/CD showed no increase of maximum LD concentration, but repeat EN supplementation to LD/CD elevated LD bioavailability and peaks. TAKE HOME MESSAGE: These pharmacokinetic data may explain the failure of the STRIDE-PD study, which aimed to show a delayed interval of dyskinesia onset with LD/CD/EN therapy. This study only allowed up titration with a fixed LD intake every 4 h. But dyskinesia occurrence may require down titration of LD dose or delay of next LD intake. PMID- 20572782 TI - The role of estrogen receptors, erbB receptors, vascular endothelial growth factor and its receptors, and vascular endothelial growth inhibitor in the development of the rat mammary gland. AB - We identified the localization and distribution of cell-specific epidermal growth factor receptors (EGFRs: erbB-1, erbB-2, erbB-3, erbB-4), vascular endothelial growth factor (VEGF), VEGF receptors [VEGFRs: VEGF-R1 (flt-1), VEGF-R2 (flk 1/KDR), VEGF-R3 (flt-4)], vascular endothelial growth inhibitor (VEGI), and estrogen receptor (ER), and determined whether or not these growth factors in rat mammary glands are functional. Thirty-five adult female Spraque-Dawley rats were randomly divided into five groups, each of which were at the 7th, 14th, and 21st day of pregnancy; 7th day post-delivery; and 7th day after weaning. It was determined that erbB, VEGF and its receptors, VEGI, and ER stained at different intensities. Intense staining was observed, in particular, in erbB receptors during pregnancy and involution, and also in VEGF and its receptors during lactation, while ER stained during the last periods of pregnancy and lactation. In conclusion, the expression of erbB, VEGF and its receptors, and ER were determined at varying intensities at different sites of the mammary gland during pregnancy, lactation, and involution periods. PMID- 20572783 TI - The ground-dwelling arthropod community of Peninsula Valdes in Patagonia, Argentina. AB - This is the first study based on a planned and intensive sampling effort that describes the community composition and structure of the ground-dwelling arthropod assemblage of Peninsula Valdes (Patagonia). It was carried out using pitfall traps, opened for two weeks during the summers of 2005, 2006 and 2007. A total of 28,111 individuals were caught. Ants(Hymenoptera: Formicidae) dominated this community, followed by beetles (Coleoptera) and spiders (Araneae). The most abundant species were Pheidole bergi Mayr (Hymenoptera:Formicidae) and Blapstinus punctulatus Solier (Coleoptera: Tenebrionidae). Two new species were very recently described as new based on specimens collected during this study: Valdesianacuriosa Carpintero, Dellape & Cheli (Hemiptera, Miridae) and Anomaloptera patagonica Dellape& Cheli (Hemiptera, Oxycarenidae). The order Coleoptera was the most diverse taxa. The distribution of abundance data was best described by the logarithmic series model both at the family and species levels, suggesting that ecological relationships in this community could be controlled by a few factors. The community was dominated by predators from a trophic perspective. This suggests that predation acts as an important factor driving the distribution and abundances of surface-dwelling arthropods in this habitat and as such serves as a key element in understanding desert, above-ground community structure. These findings may also be useful for management and conservation purposes in arid Patagonia. PMID- 20572784 TI - Stage-specific effects of population density on the development and fertility of the western tarnished plant bug, Lygus hesperus. AB - The western tarnished plant bug Lygus hesperus Knight (Heteroptera: Miridae), a major pest of cotton and other key economic crops, was tested for its sensitivity to population density during nymph and adult stages. Nymphs reared to adulthood under increasing densities in laboratory conditions exhibited incremental delays in maturation, heightened mortality rates, and reductions in body mass and various size parameters. In contrast, gonadal activity in both males and females rose with initial density increases. Supplemental nutrients provided to the nymphs failed to offset the negative effects of high density, suggesting that contact frequency, rather than resource partitioning, may be the primary stress. Unlike nymphs, newly enclosed adults exposed to increasing population densities did not suffer negative physiological effects; body mass, mortality rates and patterns of ovipositional activity were unchanged. Collectively, these results indicate that population density can dramatically influence Lygus development, but the specific effects are stage-dependent. PMID- 20572785 TI - Study of oostatic peptide uptake and metabolism in developing ovaries of the flesh fly, Neobellieria bullata. AB - The uptake and metabolism of the oostatic pentapeptide analogue of trypsin modulating oostatic factor (TMOF), H-Tyr-Asp-Pro-Ala-Pro-OH (5P), in ovaries of Neobellieria bullata (Parker) (Diptera: Sarcophagidae) were analyzed during their developmental stages. During selected stages of yolk deposition, the fate of [3HPro(3)]5P after its in vivo injection was compared to its uptake after in vitro incubation of dissected ovaries. The ovaries were analyzed from 30 s to 180 min after incubation. A detection sensitivity of 60-100 fmol of the labeled 5P was achieved using radio-high performance liquid chromatography. While the uptake of the applied radioactivity strongly depended on the stage of vitellogenesis, especially for the in vitro experiment, degradation of 5P was very quick and independent of whether the label was injected or incubated with the ovaries, regardless of the developmental stage of ovaries. No tracers of 5P were detected at 30 s after applying the labeled 5P in all tests. PMID- 20572786 TI - The pheromone of the cave cricket, Hadenoecus cumberlandicus, causes cricket aggregation but does not attract the co-distributed predatory spider, Meta ovalis. AB - Food input by the cave cricket, Hadenoecus cumberlandicus Hubble & Norton (Orthoptera: Rhaphidophoridae), is vital to the cave community, making this cricket a true keystone species. Bioassays conducted on cave walls and in the laboratory show that clustering in H. cumberlandicus is guided by a pheromone, presumably excreta. This aggregation pheromone was demonstrated by using filter paper discs that had previous adult H. cumberlandicus exposure, resulting in > 70% response by either nymphs or adults, prompting attraction (thus, active component is a volatile), followed by reduced mobility (arrestment) on treated surfaces. Adults were similarly responsive to pheromone from nymphs, agreeing with mixed stage composition of clusters in the cave. Effects of [0.001 M - 0.1 M] uric acid (insect excreta's principle component) on H. cumberlandicus behavior were inconsistent. This pheromone is not a host cue (kairomone) and is not used as a repellent (allomone) as noted through lack of responses to natural H. cumberlandicus pheromone and uric acid concentrations by a co-occurring predatory cave orb weaver spider, Meta ovalis Gertsch (Araneae: Tetragnathidae). This pheromone is not serving as a sex pheromone because nymphs were affected by it and because this population of H. cumberlandicus is parthenogenic. The conclusion of this study is that the biological value of the aggregation pheromone is to concentrate H. cumberlandicus in sheltered sites in the cave conducive for minimizing water stress. Rather than signaling H. cumberlandicus presence and quality, the reduced mobility expressed as a result of contacting this pheromone conceivably may act as a defense tactic (antipredator behavior) against M. ovalis, which shares this favored habitat site. PMID- 20572787 TI - Spatio-temporal dynamics of caddisflies in streams of southern Western Ghats. AB - The dynamics of physico-chemical factors and their effects on caddisfly communities were examined in 29 streams of southern Western Ghats. Monthly samples were collected from the Thadaganachiamman stream of Sirumalai Hills, Tamil Nadu from May 2006 to April 2007. Southwest and northeast monsoons favored the existence of caddisfly population in streams. A total of 20 caddisfly taxa were collected from 29 streams of southern Western Ghats. Hydropsyche (Trichoptera: Hydropsychidae) were more widely distributed throughout sampling sites than were the other taxa. Canonical correspondence analysis showed that elevation was a major variable and pH, stream order, and stream substrates were minor variables affecting taxa richness. These results suggested that habitat heterogeneity and seasonal changes were stronger predictors of caddisfly assemblages than large-scale patterns in landscape diversity. PMID- 20572788 TI - Life cycle of the water scorpion, Laccotrephes japonensis, in Japanese rice fields and a pond. AB - A Laccotrephes japonensis (Nepidae: Heteroptera) population was studied based upon mark and recapture censuses in order to elucidate the seasonal pattern of habitat utilization in a rice paddy system including an irrigation pond between April and October, in 2006 and 2007. The seasonal pattern of nymphs and adults did not differ markedly between the rice fields and the pond. Survival rates of L. japonensis of all stages did not differ between the rice fields and the pond in 2006, but were lower in 2007 in both habitats. In 2007, however, the survival rate of L. japonensis nymphs in the pond was higher than in the rice fields. In rice fields, 36.3% of the overwintering adults were recaptured the following year. On the other hand, the recapture rate after overwintering in the pond was only 6.4%. Migration from the pond to the paddies and vice versa was observed. In summary, the rice fields and the pond may reinforce each other as reproductive and overwintering sites of L. japonensis, especially during unfavorable years. PMID- 20572789 TI - Biotechnological approaches to develop bacterial chitinases as a bioshield against fungal diseases of plants. AB - Fungal diseases of plants continue to contribute to heavy crop losses in spite of the best control efforts of plant pathologists. Breeding for disease-resistant varieties and the application of synthetic chemical fungicides are the most widely accepted approaches in plant disease management. An alternative approach to avoid the undesired effects of chemical control could be biological control using antifungal bacteria that exhibit a direct action against fungal pathogens. Several biocontrol agents, with specific fungal targets, have been registered and released in the commercial market with different fungal pathogens as targets. However, these have not yet achieved their full commercial potential due to the inherent limitations in the use of living organisms, such as relatively short shelf life of the products and inconsistent performance in the field. Different mechanisms of action have been identified in microbial biocontrol of fungal plant diseases including competition for space or nutrients, production of antifungal metabolites, and secretion of hydrolytic enzymes such as chitinases and glucanases. This review focuses on the bacterial chitinases that hydrolyze the chitinous fungal cell wall, which is the most important targeted structural component of fungal pathogens. The application of the hydrolytic enzyme preparations, devoid of live bacteria, could be more efficacious in fungal control strategies. This approach, however, is still in its infancy, due to prohibitive production costs. Here, we critically examine available sources of bacterial chitinases and the approaches to improve enzymatic properties using biotechnological tools. We project that the combination of microbial and recombinant DNA technologies will yield more effective environment-friendly products of bacterial chitinases to control fungal diseases of crops. PMID- 20572790 TI - Disease resistance in the drywood termite, Incisitermes schwarzi: does nesting ecology affect immunocompetence? AB - Termites live in nests that can differ in microbial load and thus vary in degree of disease risk. It was hypothesized that termite investment in immune response would differ in species living in nest environments that vary in the richness and abundance of microbes. Using the drywood termite, Incisitermes schwarzi Banks (Isoptera: Kalotermitidae), as a model for species having low nest and cuticular microbial loads, the susceptibility of individuals and groups to conidia of the entomopathogenic fungus, Metarhizium anisopliae Sorokin (Hypocreales: Clavicipitaceae), was examined. The survivorship of I. schwarzi was compared to that of the dampwood termite, Zootermopsis angusticollis Hagen (Termopsidae), a species with comparatively high microbial loads. The results indicated that I. schwarzi derives similar benefits from group living as Z. angusticollis: isolated termites had 5.5 times the hazard ratio of death relative to termites nesting in groups of 25 while termites in groups of 10 did not differ significantly from the groups of 25. The results also indicated, after controlling for the influence of group size and conidia exposure on survivorship, that Z. angusticollis was significantly more susceptible to fungal infection than I. schwarzi, the former having 1.6 times the hazard ratio of death relative to drywood termites. Thus, disease susceptibility and individual investment in immunocompetence may not be dependent on interspecific variation in microbial pressures. The data validate prior studies indicating that sociality has benefits in infection control and suggest that social mechanisms of disease resistance, rather than individual physiological and immunological adaptations, may have been the principle target of selection related to variation in infection risk from microbes in the nest environment of different termite species. PMID- 20572791 TI - Synchronized expression of two caspase family genes, ice-2 and ice-5, in hydrogen peroxide-induced cells of the silkworm, Bombyx mori. AB - Caspase family proteins play important roles in different stages of the apoptotic pathway. To date, however, functions of Bombyx mori L. (Lepidoptera: Bombycidae) caspase family genes are poorly known. This paper focuses on the morphology, mitochondrial membrane potential, and expression profiles of two novel B. mori caspase family genes (ice-2 and ice-5) in 3 microM hydrogen peroxide (H2O2) damaged B. mori cells, which were separated from the ovary of B. mori. In addition, comparisons were made between damage caused by H2O2 and by ultraviolet (UV) irradiation. The results showed that the potential change of the mitochondrial membrane occurred at 0.5 h after H2O2 stimulation, which was sooner than occurred in the UV treated model where the obvious decrease appeared at 6 h after stimulation. In addition, the total change in the potential of the mitochondrial membrane in H2O2 treated B. mori cells was larger than with UV treated cells during the whole process. Analysis of fluorescent quantitative real time PCR demonstrated that ice-2 and ice-5 might be involved in both H2O2 and UV induced apoptosis in B. mori cells. Notably, after exposure to H2O2, the expression patterns of ice-5 were remarkably higher than those of ice-2, while the result was the opposite after exposure to UV irradiation. The data indicate that apoptosis induced by H2O2 was directly related to the mitochondrial pathway. The two isoforms of B. mori ice may play different roles in the mitochondrion associated apoptotic pathway in B. mori cells, and the apoptotic pathway in H2O2 induced B. mori cells is different from the UV induced apoptotic pathway. PMID- 20572792 TI - Determination of pH in regions of the midguts of acaridid mites. AB - The pH of the guts of mites strongly affects their digestive processes. This study was carried out to determine the pH in the guts of 12 species of stored product and house dust mites. Eighteen pH indicators were chosen and offered to the mites in the feeding biotest. Based on the color changes of the indicators, the gut contents of acaridid mites were determined to be within a pH range of 4 to neutral. The gut contents showed a gradient in pH from the anterior to the posterior part. The anterior midgut (ventriculus and caeca) of most species had a pH ranging from 4.5 to 5, or slightly more alkaline for most of the species, while the middle midgut (intercolon/colon) had a pH of 5 to 6. Finally, the pH of the posterior midgut (postcolon) was between 5.5 and 7. Except for Dermatophagoides spp., no remarkable differences in the pH of the gut were observed among the tested species. Dermatophagoides spp. had a more acidic anterior midgut (a pH of 4 to 5) and colon (a pH of 5) with postcolon (a pH of below 6). The results characterizing in vivo conditions in the mite gut offer useful information to study the activity of mite digestive enzymes including their inhibitors and gut microflora. PMID- 20572794 TI - Biotechnological implications from abscisic acid (ABA) roles in cold stress and leaf senescence as an important signal for improving plant sustainable survival under abiotic-stressed conditions. AB - In the past few years, the signal transduction of the plant hormone abscisic acid (ABA) has been studied extensively and has revealed an unanticipated complex. ABA, characterized as an intracellular messenger, has been proven to act a critical function at the heart of a signaling network operation. It has been found that ABA plays an important role in improving plant tolerance to cold, as well as triggering leaf senescence for years. In addition, there have been many reports suggesting that the signaling pathways for leaf senescence and plant defense responses may overlap. Therefore, the objective was to review what is known about the involvement of ABA signaling in plant responses to cold stress and regulation of leaf senescence. An overview about how ABA is integrated into sugars and reactive oxygen species signaling pathways, to regulate plant cold tolerance and leaf senescence, is provided. These roles can provide important implications for biotechnologically improving plant cold tolerance. PMID- 20572795 TI - A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults. AB - The relationship between deoxynivalenol (DON) intake and first morning urinary DON was examined in UK adults to validate the latter as a biomarker of human exposure. DON was assessed in first morning samples collected during a period of normal diet, a wheat-restriction intervention diet, and partial wheat-restriction intervention in which bread was allowed. During the partial intervention duplicate bread portions were collected for DON analysis. During the normal diet, partial intervention and full intervention, urinary DON was detected in 198/210 (geometric mean 10.1 ng DON mg(-1) creatinine, 95% confidence interval (CI) 8.6 11.6 ng mg(-1); range nd-70.7 ng mg(-1)), in 94/98 (5.9 ng mg(-1), 95% CI 4.8-7.0 ng mg(-1); range nd-28.4 ng mg(-1)), and 17/40 (0.5 ng mg(-1), 95% CI 0.3-0.7 ng mg(-1); range nd-3.3 ng mg(-1)) volunteers, respectively. A strong correlation between DON intake and the urinary biomarker was observed (p <0.001, adjusted r(2) = 0.83) in models adjusting for age, sex and body mass index. These data demonstrate a quantitative correlation between DON exposure and urinary DON, and serve to validate the use of urinary DON as an exposure biomarker. PMID- 20572796 TI - Biodiesel production from Jatropha curcas: a critical review. AB - The fuel crisis and environmental concerns, mainly due to global warming, have led researchers to consider the importance of biofuels such as biodiesel. Vegetable oils, which are too viscous to be used directly in engines, are converted into their corresponding methyl or ethyl esters by a process called transesterification. With the recent debates on "food versus fuel," non-edible oils, such as Jatropha curcas, are emerging as one of the main contenders for biodiesel production. Much research is still needed to explore and realize the full potential of a green fuel from J. curcas. Upcoming projects and plantations of Jatropha in countries such as India, Malaysia, and Indonesia suggest a promising future for this plant as a potential biodiesel feedstock. Many of the drawbacks associated with chemical catalysts can be overcome by using lipases for enzymatic transesterification. The high cost of lipases can be overcome, to a certain extent, by immobilization techniques. This article reviews the importance of the J. curcas plant and describes existing research conducted on Jatropha biodiesel production. The article highlights areas where further research is required and relevance of designing an immobilized lipase for biodiesel production is discussed. PMID- 20572793 TI - Differential gene expression from midguts of refractory and susceptible lines of the mosquito, Aedes aegypti, infected with Dengue-2 virus. AB - Suppressive subtractive hybridization was used to evaluate the differential expression of midgut genes of feral populations of Aedes aegypti (Diptera: Culicidae) from Colombia that are naturally refractory or susceptible to Dengue-2 virus infection. A total of 165 differentially expressed sequence tags (ESTs) were identified in the subtracted libraries. The analysis showed a higher number of differentially expressed genes in the susceptible Ae. aegypti individuals than the refractory mosquitoes. The functional annotation of ESTs revealed a broad response in the susceptible library that included immune molecules, metabolic molecules and transcription factors. In the refractory strain, there was the presence of a trypsin inhibitor gene, which could play a role in the infection. These results serve as a template for more detailed studies aiming to characterize the genetic components of refractoriness, which in turn can be used to devise new approaches to combat transmission of dengue fever. PMID- 20572798 TI - Erythropoiesis-stimulating agents in myelodysplastic syndromes. PMID- 20572797 TI - Altered gene expression in human adipose stem cells cultured with fetal bovine serum compared to human supplements. AB - Mesenchymal stromal cells (MSCs) are promising candidates for innovative cell therapeutic applications. For clinical scale manufacturing regulatory agencies recommend to replace fetal bovine serum (FBS) commonly used in MSC expansion media as soon as equivalent alternative supplements are available. We already demonstrated that pooled blood group AB human serum (HS) and thrombin-activated platelet releasate plasma (tPRP) support the expansion of multipotent adipose tissue-derived MSCs (ASCs). Slight differences in size, growth pattern and adhesion prompted us to investigate the level of equivalence by compiling the transcriptional profiles of ASCs cultivated in these supplements. A whole genome gene expression analysis was performed and data verified by polymerase chain reaction and protein analyses. Microarray-based screening of 34,039 genes revealed 102 genes differentially expressed in ASCs cultured with FBS compared to HS or tPRP supplements. A significantly higher expression in FBS cultures was found for 90 genes (fold change >=2). Only 12 of the 102 genes showed a lower expression in FBS compared to HS or tPRP cultures (fold change <=0.5). Differences between cells cultivated in HS and tPRP were hardly evident. Supporting previous observations of reduced adhesion of cells cultivated in the human alternatives we detected a number of adhesion and extracellular matrix associated molecules expressed at lower levels in ASCs cultivated with human supplements. Confirmative assays analyzing transcript or protein expression with selected genes supported these results. Likewise a number of mesodermal differentiation-associated genes were higher expressed in cells grown in FBS. Quantifying adipogenic and osteogenic differentiation lacked to demonstrate a clear correlation to the supplement due to donor-specific variances. Our results emphasize the necessity of comparability studies as they indicate that FBS induces a culture adaptation exceeding that of ex vivo culture in human supplements and thus may contribute to the therapeutic potential. PMID- 20572799 TI - Potential biomarkers of bortezomib activity in mantle cell lymphoma from the phase 2 PINNACLE trial. AB - Immunohistochemical analyses of archival tumor specimens were used for pre planned exploratory analyses of protocol-specified candidate biomarkers of bortezomib activity in 73 patients with relapsed/refractory mantle cell lymphoma in the phase 2 PINNACLE study. Consistent with other studies, elevated Ki-67 was a marker of poor prognosis, demonstrating significant associations with shorter time to progression and overall survival. Elevated NF-kappaB p65 and low PSMA5 expression demonstrated a trend for better response and were significantly associated with longer time to progression; elevated NF-kappaB p65 demonstrated a trend toward longer overall survival. This is consistent with myeloma clinical genomics research, suggesting biomarker relevance across tumor types. Elevated p27 was significantly associated with longer overall survival. Overall survival analyses by International Prognostic Index and Mantle Cell Lymphoma International Prognostic Index confirmed differential prognosis by both scores. These biomarkers data begin to illuminate bortezomib's mechanism of action in lymphoma. PMID- 20572800 TI - Primary hematolymphoid malignancies involving the extrahepatic bile duct or gallbladder. AB - Primary hematolymphoid malignancies of the extrahepatic biliary tract are rare tumors. We report five cases of primary hematolymphoid malignancies involving the extrahepatic biliary tract. One is a granulocytic sarcoma of the extrahepatic bile duct, another is an extramedullary plasmacytoma of the gallbladder, and the others are two non-Hodgkin lymphomas of the extrahepatic bile duct and one of the gallbladder. The clinical presentations, radiographic studies, and gross findings at surgery have not been a significant help in differential diagnosis. Although a preoperative diagnosis of primary hematolymphoid malignancy is very difficult to reach because of the rarity of this disease, it should be considered, because, if an accurate diagnosis is made before surgical intervention, chemotherapy is the most appropriate treatment. In limited cases mimicking cholangiocarcinoma and gallbladder cancer, surgical resection followed by chemotherapy has a valid role as reasonable treatment for patients. PMID- 20572801 TI - Sustained, durable responses with alemtuzumab in refractory angioimmunoblastic T cell lymphoma. PMID- 20572802 TI - Cancer and chlordane-treated homes: a pinch of prevention is worth a pound of cure. PMID- 20572805 TI - ESVS Guidelines: Section B - diagnosis and investigation of patients with carotid stenosis. AB - Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis. PMID- 20572806 TI - ESVS Guidelines: Section A--prevention in patients with carotid stenosis. AB - Herein, we present the European Society for Vascular Surgery Guidelines pertinent to the secondary prevention of cerebrovascular events in patients with carotid artery stenosis including lipid lowering therapy, antiplatelet therapy and other risk factor modification. These recommendations are based on current evidence from clinical trials. There is a need for aggressive prevention treatment in patients with carotid artery disease. We also discuss the diagnosis and grading of carotid artery stenosis. PMID- 20572807 TI - Current topics on hypolipidaemic therapy and cardiovascular risk assessment. PMID- 20572808 TI - Endocytosis of hyaluronidase-1 by the liver. AB - It has been suggested that intracellular Hyal-1 (hyaluronidase-1), which is considered a lysosomal enzyme, originates via endocytosis of the serum enzyme. To test this proposal we have investigated the uptake and intracellular distribution of rhHyal-1 (recombinant human Hyal-1) by mouse liver, making use of centrifugation methods. Experiments were performed on wild-type mice injected with 125I-labelled rhHyal-1 and on Hyal-1-/- mice injected with the unlabelled enzyme, which were killed at various times after injection. Activity of the unlabelled enzyme was determined by zymography. Intracellular distribution of Hyal-1 was investigated by differential and isopycnic centrifugation. The results of the study indicated that rhHyal-1 is endocytosed by the liver, mainly by sinusoidal cells, and follows the intracellular pathway described for many endocytosed proteins that are eventually located in lysosomes. However, Hyal-1 endocytosis has some particular features. First, endocytosed rhHyal-1 is quickly degraded. Secondly, its distribution, as analysed by differential centrifugation, differs from the distribution of beta-galactosidase, taken as the reference lysosomal enzyme. Further analysis by isopycnic centrifugation in a sucrose gradient shows endocytosed rhHyal-1 behaves like beta-galactosidase shortly after injection. However the Hyal-1 distribution is markedly less affected than beta galactosidase, following a prior injection of Triton WR-1339, which is a specific density perturbant of lysosomes. The behaviour in centrifugation of endogenous liver Hyal-1, identified by hyaluronan zymography, exhibits some similarity with the behaviour of the endocytosed enzyme, suggesting that it could originate from endocytosis of the serum enzyme. Overall, these results can be explained by supposing that active endocytosed Hyal-1 is mainly present in early lysosomes. Although its degradation half-time is short, Hyal-1 could exert its activity due to a constant supply of active molecules from the blood. PMID- 20572804 TI - Ribonucleoprotein multimers and their functions. AB - Ribonucleoproteins (RNPs) play key roles in many cellular processes and often function as RNP enzymes. Similar to proteins, some of these RNPs exist and function as multimers, either homomeric or heteromeric. While in some cases the mechanistic function of multimerization is well understood, the functional consequences of multimerization of other RNPs remain enigmatic. In this review we will discuss the function and organization of small RNPs that exist as stable multimers, including RNPs catalyzing RNA chemical modifications, telomerase RNP, and RNPs involved in pre-mRNA splicing. PMID- 20572809 TI - Docking of protein kinase B inhibitors: implications in the structure-based optimization of a novel scaffold. AB - Protein kinase B (PKB/AKT) is an attractive therapeutic target in anticancer drug development. We have recently identified by docking-based virtual screening a low micromolar AKT-2 inhibitor. Additionally, the virtual screening hit represents a novel AKT-2 inhibitor scaffold. In this work, we discuss a structure-based design strategy toward the optimization of this hit. Following this strategy and using a herein validated docking protocol, we conducted the design of novel compounds with expected improved activity over the parent compound. The newly designed molecules have high predicted affinity for AKT-2; are synthetically accessible and are contained within the kinase-relevant property space. PMID- 20572810 TI - The mimic of type II aldolases chemistry: asymmetric synthesis of beta-hydroxy ketones by direct aldol reaction. AB - An efficient direct aldol reaction has been developed for the synthesis of chiral beta-hydroxy ketone using a combination of C(1)-symmetric chiral prolinamides based on o-phenylenediamine and zinc triflate as catalyst. The reaction was convenient to carry out in aqueous media with up to 98% chemical yields and up to 94% ee values. The current strategy can be regarded as the analogue of aldolase type II, which suggests a new pathway for the designing of new organocatalysts. PMID- 20572811 TI - Design, biologic evaluation, and SAR of novel pseudo-peptide incorporating benzheterocycles as HIV-1 protease inhibitors. AB - A series of novel HIV-1 protease inhibitors based on the (hydroxyethylamino) sulfonamide isostere incorporating substituted phenyls and benzheterocycle derivatives bearing rich hydrogen bonding acceptors as P(2) ligands were synthesized. Prolonged chain linking the benzhereocycle to the carbonyl group resulted in partial loss of binding affinities. Introduction of a small alkyl substituent with appropriate size to the -CH2- of P(1)-P(2) linkage as a side chain resulted in improved inhibitory potency, and in this study, isopropyl was the best side chain. Replacement of the isobutyl substituent at P(1)'group with phenyl substituent decreased the inhibitory potency. One of the most potent inhibitor, compound 23 showing high affinity to HIV-1 protease with an IC(50) value of 5 nM, also exhibited good anti-SIV activity (EC(50) = 0.8 microM) with low toxicity (TC(50) > 100 microM). The flexible docking of inhibitor 23 to HIV-1 protease active site rationalized the interactions with protease. PMID- 20572812 TI - A novel pharmacophore model for the design of anthrax lethal factor inhibitors. AB - This study aims at the identification of novel structural features on the surface of the Zn-dependent metalloprotease lethal factor (LF) from anthrax onto which to design novel and selective inhibitors. We report that by targeting an unexplored region of LF that exhibits ligand-induced conformational changes, we could obtain inhibitors with at least 30-fold LF selectivity compared to two other most related human metalloproteases, MMP-2 and MMP-9. Based on these results, we propose a novel pharmacophore model that, together with the preliminarily identified compounds, should help the design of more potent and selective inhibitors against anthrax. PMID- 20572813 TI - A peptide from the beta-strand region of CD2 protein that inhibits cell adhesion and suppresses arthritis in a mouse model. AB - Cell adhesion molecules play a central role at every step of the immune response. The function of leukocytes can be regulated by modulating adhesion interactions between cell adhesion molecules to develop therapeutic agents against autoimmune diseases. Among the different cell adhesion molecules that participate in the immunologic response, CD2 and its ligand CD58 (LFA-3) are two of the best characterized adhesion molecules mediating the immune response. To modulate the cell adhesion interaction, peptides were designed from the discontinuous epitopes of the beta-strand region of CD2 protein. The two strands were linked by a peptide bond. beta-Strands in the peptides were nucleated by inserting a beta sheet-inducing Pro-Gly sequence with key amino acid sequences from CD2 protein that binds to CD58. Using a fluorescence assay, peptides that exhibited potential inhibitory activity in cell adhesion were evaluated for their ability to bind to CD58 protein. A model for peptide binding to CD58 protein was proposed based on docking studies. Administration of one of the peptides, P3 in collagen-induced arthritis in the mouse model, indicated that peptide P3 was able to suppress rheumatoid arthritis in mice. PMID- 20572814 TI - Diabetic eye disease among adults in Fiji with self-reported diabetes. AB - BACKGROUND: To characterize diabetic eye disease and its management among adults aged >=40 years with self-reported diabetes in Fiji. METHODS: During a population based cross-sectional survey using multistage cluster random sampling, participants reported health information, including whether a doctor had diagnosed diabetes. HbA1c and visual acuity were measured. Diabetic eye disease was assessed using 90-dioptre lens dilated funduscopy. RESULTS: Of those enumerated, 1381 (73.0%) participated, with 222 reporting diabetes. Twenty fundi were not examined (19 due to cataract). Of the remaining 424 eyes, 75.5% had no diabetic disease, 1.2% had proliferative retinopathy, 7.5% had active significant maculopathy and 0.7% had burnt-out/treated disease. By person, 27.2% had retinopathy and/or maculopathy in at least one eye. Mean HbA1c (9.9 +/- 2.3%) for this group was significantly higher (P = 0.004) than for those without eye disease. Vision-threat occurred in at least one eye of 11.5%. Diabetes (predominantly maculopathy) caused pinhole acuity <6/18, <6/60 and <3/60 for 3.8%, 1.1% and 0.7% of eyes, respectively. No person was bilaterally blind (<6/60) due to diabetes, but 2.3% (all on oral antiglycaemics alone) were 6/60 bilaterally. Compared with recent diabetes diagnosis, diagnosis >10 years ago was predictive of any (odds ratio [OR] 8.13; 95% confidence interval [CI] 3.28-20.21; P < 0.001) and vision-threatening (OR 5.25; 95% CI 1.71-16.12; P = 0.004) eye disease. Although 80.6% claimed regular general diabetes checkups, only 36.5% recalled previous dilated ocular examination. Four eyes had received laser treatment. CONCLUSION: There was evidence of failure of management of diabetes and its eye complications. Both need to be improved if increasing diabetes related visual disability is to be avoided. PMID- 20572815 TI - Changes in Caucasian eyes after laser peripheral iridotomy: an anterior segment optical coherence tomography study. AB - BACKGROUND: To evaluate by anterior segment optical coherence tomography (AS-OCT) the changes in the anterior chamber structures in Caucasian eyes after laser peripheral iridotomy (PI). METHODS: Retrospective study of consecutive Caucasian primary angle closure suspect (PACS), primary angle closure (PAC) or primary angle closure glaucoma (PACG) patients who underwent laser PI over a 25-month period at a specialist glaucoma practice. The AS-OCT images of the temporal and nasal angles (in light and dark) before and after laser PI were analysed. The parameters studied were trabecular-iris angle (TIA), angle opening distance (AOD), trabecular-iris space area (TISA), trabecular-iris contact length (TICL), iris thickness (IT) and maximum iris bow height (MIBH). RESULTS: Images of 71 eyes of 71 patients were assessed. The mean age at laser PI was 60.3 +/- 10.0 years. Forty (56.3%) were women, and 14 (19.7%) had PACG. The mean time from laser PI to the follow-up AS-OCT scan was 5.92 +/- 3.22 weeks. The IT did not alter significantly after laser PI, but there were significant increases in the TIA, AOD and TISA, as well as a significant decrease in MIBH, in both light and dark. There was no difference in the magnitude of change seen between the temporal and nasal angles, or between PACS/PAC and PACG eyes. CONCLUSION: In Caucasian eyes, laser PI resulted in significant angle widening (increased TIA, AOD and TISA) and iris profile flattening (decreased MIBH) at the temporal and nasal angles based on AS-OCT imaging in both light and dark. PMID- 20572816 TI - Bilateral sequential uveal effusion syndrome after one-quarter of a century. PMID- 20572818 TI - Evolution of retinitis sclopetaria after blunt trauma: comment. PMID- 20572819 TI - Differences in contrast sensitivity between monofocal, multifocal and accommodating intraocular lenses: long-term results. AB - BACKGROUND: To evaluate long-term contrast sensitivity (CS) and visual acuity following implantation of monofocal, accommodating, refractive and diffractive multifocal intraocular lenses (IOLs) in patients with unilateral cataract. METHODS: In this prospective non-randomized clinical trial, 87 patients with unilateral cataract were enrolled in four groups for phacoemulsification and IOL implantation in Ophthalmology Department of Goztepe Training and Research Hospital. Twenty-four patients had monofocal (Alcon Acrysof; group 1), 21 patients accommodating (Human Optics 1CU; group 2), 22 patients diffractive multifocal (Tecnis ZM900; group 3) and 20 patients refractive multifocal (AMO Rezoom; group 4) IOL implantations. Ages of patients were between 40 and 70. Parameters analysed at the 18th postoperative month were subjective refractions, monocular and binocular distance and near photopic CSs, visual acuities. RESULTS: Near visual acuities were statistically better in group 3 than the other groups (P < 0.05). At low spatial frequencies, mean monocular distance CSs of group 1 and mean monocular near CSs of groups 1 and 2 were statistically higher than those of group 4 (P < 0.05). There was no significant difference between binocular CSs of group 4 and the other groups at low spatial frequencies. At high spatial frequencies, monocular and binocular CSs of groups 1 and 2 were statistically higher than those of groups 3 and 4 (P < 0.05). Near CSs was better in group 3 than group 4. CONCLUSIONS: In patients with unilateral cataract, monofocal, accommodating and partially diffractive multifocal IOL provided higher CS scores when compared with refractive multifocal IOL and in multifocal IOL groups binocular CSs were better than monocular CSs when compared with other groups. PMID- 20572820 TI - Diabetic retinopathy in a hospital eye clinic population in Honiara, Solomon Islands. AB - BACKGROUND: To determine the presence, severity and context of diabetic retinopathy among diabetic adults using hospital eye clinic services in Honiara, Solomon Islands. METHODS: Fifty consecutive known diabetic patients aged >=20 years were interviewed and underwent Snellen distance vision testing and complete ocular examination, including dilated 90 D funduscopy. Diabetic retinopathy was graded according to the International Clinical Diabetic Retinopathy and Macular Oedema Disease Severity Scales. RESULTS: Participants were predominantly Melanesian (94%). Mean age was 53.6 +/- 10.7 years; 42% were female; and 34% were rural dwellers. Diabetes had been diagnosed <5, 5-10 and >10 years ago for 42%, 34% and 24% of participants. However, 54% denied ever having had a dilated fundus examination. Proliferative retinopathy, severe non-proliferative changes and maculopathy were present in 5, 12 and 26 eyes, respectively. For the 32 eyes with pinhole acuity <=6/12, diabetic eye disease was the cause for 20, with all but one due to maculopathy. Diabetes reduced the pinhole vision of five eyes to <=6/60. Twenty-four per cent of participants had diabetes-related pinhole vision <=6/12 in at least one eye. Those diagnosed with diabetes 5-10 and >10 years were 17.5 and 58.8 times more likely to have such an eye compared with those recently (<5 years) diagnosed (extended Mantel-Haenszel chi2 = 11.570, P < 0.001). Participants were not well informed about diabetic eye disease. CONCLUSIONS: Diabetic eye disease is now a significant contributor to this clinic's workload. A population-based survey is needed to quantify the problem and inform design and delivery of eye services for this chronic disease. PMID- 20572821 TI - Effect of stem cells and fibrin concentration on the vascularization of the Medpor orbital implant. AB - BACKGROUND: To determine the effect of adipose-derived adult stem cells (ADASCs) and optimal concentration of fibrin on fibrovascular ingrowth into porous polyethylene orbital implants (Medpor). METHODS: Medpor sheet treated with O.25% fibrin only and ADASCs in mixtures containing fibrin (0.25%, 0.5% or 1.25%) were applied to a Medpor sheet and implanted in the back of each of 20 athymic nude mice. After 10 days, implants were removed and observed for fibrovascularization and stability. Haemoglobin, collagen and cellular DNA content were determined in quantitative assays. RESULTS: Haemoglobin, collagen and cellular DNA levels were significantly higher in ADASC group than in the cell-free implant (0.25% fibrin only) group (P < 0.01). The level of haemoglobin and collagen content was significantly higher in the ADASC + 0.5% fibrin group among the ADASC and fibrin mixtures (P < 0.01). CONCLUSION: ADASCs significantly improved fibrovascularization on Medpor compared with implants alone. Fibrin, used together with ADASCs to potentiate fibrovascularization, was most effective at concentrations of 0.5%. PMID- 20572822 TI - Phacoemulsification in posterior polar cataract: does size of lens opacity affect surgical outcome? AB - BACKGROUND: To study the effect of size of the posterior polar opacity on surgical and visual outcome of phacoemulsification in posterior polar cataract. SETTING: Post Graduate Institute of Medical Education and Research, Chandigarh, India. METHODS: Consecutive patients with posterior polar cataract who underwent phacoemulsification were analysed for intraoperative complications and postoperative outcome. The continuous curvilinear capsulorhexis size was kept approximately 5.5 mm, and hydrodelineation was done instead of hydrodissection. RESULTS: There were 58 eyes of 51 patients who underwent phacoemulsification for posterior polar cataract. The mean follow-up time was 15.4 months (range 12-40 months). Twenty-three eyes had size of polar opacities 4 mm or more in diameter whereas 35 eyes had less than 4 mm. Posterior capsule rupture occurred in nine eyes (15.51%). In eyes with polar opacities 4 mm or more, seven (30.43%) had posterior capsule rupture whereas in eyes with less than 4 mm size, only two (5.71%) had posterior capsule rupture. Capsular bag placement of intraocular lens (IOL) was achieved in 50 eyes and sulcus-sulcus in eight eyes. Three-piece hydrophobic acrylic IOL was implanted in 47 eyes and all polymethylmethacrylate IOL in 11 eyes. Postoperatively best-corrected visual acuity of 6/12 or better was achieved in 55 eyes (94.8%) and three eyes achieved 6/24 or less. CONCLUSION: Phacoemulsification in eyes with larger size of polar opacity has significant risk of posterior capsule rupture. PMID- 20572823 TI - Comparison of biomechanical parameters in penetrating keratoplasty and normal eyes using the Ocular Response Analyser. AB - BACKGROUND: To compare corneal hysteresis (CH) and corneal resistance factor (CRF) in eyes 1 year following penetrating keratoplasty (PK) with that of normal eyes using the Ocular Response Analyser. METHODS: Prospective case comparison of 166 normal right eyes and 34 unilateral post-PK eyes presenting to a teaching hospital in Birmingham, UK. The CH, CRF and Goldmann-correlated intraocular pressure, of each eye was measured using the Ocular Response Analyser. The central corneal thickness (CCT) was measured using an ultrasonic pachymeter. RESULTS: The mean CH was 10.6 +/- 2.0 mmHg, standard deviation (SD) and CRF was 10.2 +/- 2.0 mmHg (SD) in normal eyes and 8.9 +/- 3.3 mmHg and 8.1 +/- 3.3 mmHg in post-PK eyes, respectively. The mean CCT was 541.8 +/- 36.1 um in normal eyes and 556.0 +/- 69.2 um in post-PK eyes. The Goldmann-correlated intraocular pressure was 16.1 +/- 3.1 mmHg and 12.4 +/- 2.9 mmHg in normal eyes and post-PK eyes, respectively. The CCT was found to be higher in post-PK eyes compared with normal eyes but the difference was not statistically significant (P > 0.5). CONCLUSION: Reduced biomechanical measures were found in post-PK eyes despite a higher mean CCT. This may be due to the altered corneal structure following PK. PMID- 20572824 TI - Factors affecting visual outcome in herpes zoster ophthalmicus: a prospective study. AB - PURPOSE: To evaluate visual outcome and factors affecting visual outcome in herpes zoster ophthalmicus (HZO). METHODS: A prospective, longitudinal, observational study was undertaken in 64 consecutive patients with HZO presenting within 72 h of rash onset. Patients underwent detailed ophthalmological and dermatological examinations at presentation, with follow up at first, second and fourth weeks and third and sixth months. All patients received both systemic and topical acyclovir. The main outcome measure was best-corrected visual acuity at 6 months' follow up. Local and systemic factors were correlated with visual outcome using univariate and multivariate analyses. RESULTS: Overall visual outcome was good, with 36/64 (56.3%) patients having a visual acuity of 6/6 or better. Mild visual loss occurred in 22/64 (34.3%), moderate loss in 3/64 (4.7%) and severe loss in 3/64 (4.7%); moderate to severe visual loss was due to severe uveitis (2), neurotrophic keratitis (1) and cataract (3). Increasing age (P = 0.04), positive Hutchinson sign (P = 0.001), absent corneal sensation (P = 0.01), corneal epithelial lesions (P = 0.03) and uveitis (P < 0.001) were significantly associated with visual loss. Uveitis was found to be the best predictor of visual loss in HZO on multivariate analysis. CONCLUSION: The overall visual outcome is good in HZO patients receiving antiviral therapy. Hutchinson's sign and anterior uveitis were found to be strong predictors of visual loss in HZO. Presence of these predictors calls for close monitoring. PMID- 20572825 TI - Abnormal cytokeratin expression in low-grade conjunctival intraepithelial neoplasia. PMID- 20572826 TI - Periocular injections of triamcinolone for sympathetic ophthalmia. PMID- 20572827 TI - Primary trabeculectomy with mitomycin C: safety and efficacy at 2 years. AB - PURPOSE: To examine the rates of intermediate-term intraocular pressure (IOP) control after trabeculectomy with adjunctive mitomycin C (MMC) and assess for associated complications. METHODS: Medical records of patients undergoing primary trabeculectomy with MMC at Concord Repatriation Hospital, Sydney between January 1997 and December 2005 were reviewed. All eyes with a minimum of 2-year follow up were included. Follow-up data were collected in a standardized form on postoperative IOP, bleb-related and other complications. Success was measured as IOP <= 18 mmHg and >= 6 mmHg (criteria 1) with (qualified success) or without (absolute success) the use of glaucoma medications. A secondary outcome measure was an IOP reduction of greater than 20% from baseline (criteria 2). Eyes with preoperative IOP of 18 mmHg or less were included, but also analysed separately to those eyes with preoperative IOP above 18 mmHg. RESULTS: Sixty eyes from 42 patients were included in the study, with 3-year follow up on 48 eyes. Mean preoperative IOP was 25.3 mmHg (range 8-45) and mean postoperative IOP was 14.0 mmHg at 1- and 2-year follow up, and 14.7 mmHg at 3 years (ranges: 3-31, 4-30 and 8-45 mmHg respectively). Cumulative success for criteria 1 was 85.0% at 2 years and 83.3% at 3 years, and for criteria 2 it was 80.0% and 79.2%, respectively. The number of eyes on glaucoma medications was reduced from 51 preoperatively to 30 at 3 years. Complications were infrequent. There was one eye with a shallow anterior chamber beyond the immediate postoperative period. One eye required cataract surgery at 1-year follow up. Subgroup analysis was performed using the first operated eye only, and results did not differ significantly from overall results. CONCLUSION: MMC-augmented trabeculectomy can significantly reduce IOP in the short and intermediate term, with a favourable safety profile. PMID- 20572828 TI - Correcting post-keratoplasty anisometropia with the implantable collamer phakic intraocular lens. AB - BACKGROUND: We evaluate the Visian Implantable Collamer Lens (Staar, Monrovia, CA, USA) phakic intraocular lens for treating post-keratoplasty anisometropia. METHODS: Case series of three eyes (2 phakic and 1 pseudophakic). RESULTS: The mean age was 47.3 years (range 30-73 years), with a minimum of 3-month follow up. The mean preoperative spherical equivalent was -8.75 +/- 5.17 D (-4.00 to -14.25 D) improving to -0.29 +/- 1.21 D postoperatively (range 0.75 to -1.625 D). Mean logMAR uncorrected visual acuity improved from 1.66 +/- 0.60 (6/240) preoperatively to 0.41 +/- 0.52 (6/15(2) ). Mean logMAR best spectacle-corrected visual acuity improved from 0.32 +/- 0.15 (6/12) preoperatively to 0.10 +/- 0.11 (6/7.5). Anisometropia improved from a difference of 6.37 +/- 2.59 D preoperatively to 2.09 +/- 1.37 D postoperatively, and there were no complications. CONCLUSION: Our technique for this clinical indication shows that the Visian Implantable Collamer Lens is a safe and effective alternative for treating post-keratoplasty anisometropia. PMID- 20572829 TI - Multiresistant Pseudomonas keratitis. PMID- 20572830 TI - Radiographic evaluation of marginal bone levels during healing period, adjacent to parallel-screw cylinder implants inserted in the posterior zone of the jaws, placed with flapless surgery. AB - OBJECTIVE: The purpose of this study was to compare changes at the marginal bone level adjacent to implants placed with flapless surgery and flap surgery during a stress-free healing period. MATERIAL AND METHODS: Seven hundred and eighty-five implants were placed in 417 patients with a flapless approach and 459 implants were placed in 227 patients using flap techniques. The marginal bone level was determined radiographically, using digitized panoramic radiographs, at two time points: at implant placement (baseline) and after the healing period. RESULTS: The median follow-up time was 0.5 years (SD, 1.2; range: 0.3-0.7). Implants placed with flapless surgery had a mean crestal bone loss of 0.5 mm (SD, 0.5; range: -0.7-2.4) and implants placed with flap surgery had a mean bone loss of 0.5 mm (SD, 0.7; range: -2.0-3.0) after healing. Differences in bone level changes between smokers and non-smokers were statistically significant for the flapless group (P<0.01). CONCLUSIONS: A radiographic evaluation of marginal bone levels adjacent to implants showed comparable results for implants placed with flapless surgery and flap surgery. Appropriate case selection after virtual planning of the implant position and a sound surgical protocol is necessary for flapless surgery. Smoking habits may compromise the efficacy of flapless implant procedures. PMID- 20572831 TI - Effect of a macroscopic groove on bone response and implant stability. AB - OBJECTIVES: The aim of this study was to investigate the effect of a macroscopic groove on bone response and implant stability during the early stages of healing using a rabbit tibia model. MATERIALS AND METHODS: Anodized titanium implants with (n=24) and without (n=24) macroscopic grooves were prepared. A total of 12 rabbits were used and each received four implants: six rabbits with implants with macroscopic grooves (test group) and six rabbits with implants without macroscopic groves (control group). Histomorphometry, resonance frequency, and removal torque value were evaluated 2 and 6 weeks post-implant-insertion. RESULTS: At 2 and 6 weeks, there was no significant difference between the two groups in the percentage of bone-to-implant contact (P>0.05). At 6 weeks, the test group had significantly higher implant stability quotient values than the control group (P<0.05). At 2 and 6 weeks, implants with grooves showed a significantly greater resistance to reverse torque than control implants (P<0.05). CONCLUSION: The groove on the oxidized titanium surface may increase both resistance to shear load and adhesion at the bone-implant interface. A geometric feature such as a macroscopic groove may facilitate osseointegration and increase implant stability in various clinical conditions. Further studies are required to confirm whether the improvement in implant stability will enhance treatment success in humans. PMID- 20572832 TI - Bone reaction adjacent to microplasma-sprayed CaP-coated oral implants subjected to occlusal load, an experimental study in the dog. Part I: short-term results. AB - BACKGROUND: A new microplasma spraying equipment (MSE) to deposit calcium phosphate ceramic (CaP) coatings onto titanium substrates has been developed. With this system, it is possible to spray fine particles and to apply textured hydroxylapatite coatings onto titanium surfaces. Moreover, due to the low heat power of the microplasma jet, overheating of the powder particles as well as excessive local overheating of the substrate is diminished. Furthermore, because of the small laminar plasma jet, it is possible to achieve high spray efficiency in the case of spraying for dental implants. Also, the low level of noise (25-50 dB) and hardly any dust makes it possible to operate MSE under conditions of normal workrooms. OBJECTIVE: The aim was to investigate, in a mandibular dog model, bone biological properties and the occlusal loading effects of titanium implants provided with newly developed microplasma-sprayed CaP coatings. MATERIAL AND METHODS: For histomorphometrical evaluation, 48 screw-type titanium implants were inserted into the mandibles of six adult beagle dogs. The implants were either acid etched without additional coating, coated with a conventionally plasma-sprayed CaP ceramic, coated with a microplasma-sprayed CaP ceramic or with a microplasma-sprayed coating at the apical part only. To assess the effect of occlusal loading, a split-mouth design was used. Six weeks after implantation, the implants in one half of the mandible of each dog were functionally loaded, while the contra lateral implants served as control. Six weeks after loading, the animals were sacrificed and bone-to-implant contact as well as the amount of bone around the implants were assessed. RESULTS: Irrespective of surface and functional load, no statistically significant differences (P>0.05) were found either for bone-to-implant contact or for the amount of bone between the various implant surfaces. On the other hand, functional loading of the non-coated implants was associated with a tendency towards crestal bone loss. CONCLUSION: Within the limits of the experiment, we conclude that functional loading of MPS CaP coatings induces a favorable bone response, and furthermore, that the bone response, irrespective of the loading condition, does not differ from conventional plasma-sprayed CaP coatings. PMID- 20572833 TI - Clinical evaluation of particulate allogeneic with and without autogenous bone grafts and resorbable collagen membranes for bone augmentation of atrophic alveolar ridges. AB - OBJECTIVES: The evaluate the clinical outcome of bone augmentation with the use of particulate mineralized freeze-dried bone allograft (FDBA) with or without the addition of autogeneous bone chips, applied in a bi-layered (BL) technique, covered by a resorbable cross-linked collagen membrane. MATERIAL AND METHODS: Fifty patients presenting with a vertical and/or lateral ridge deficiency of at least 3 mm were included: Group FDBA, N=27 patients, particulate FDBA was the only graft; and Group BL, N=23 patients, a BL bone grafting procedure where autogenous bone chips were the inner layer and FDBA the outer. Bone graft was covered with a ribose cross-linked collagen barrier membrane. Ridge dimensions were clinically or radiographically (computerized tomography scan) measured at the time of the bone augmentation procedure and at implant placement or uncovering and the maximum linear vertical or horizontal calcified tissue gain was calculated. Statistical analysis consisted of linear regression analysis, with maximum bone gain being the dependent variable. RESULTS: In the FDBA group, mean vertical bone gain was 3.47 mm (SD 1.25) and the horizontal, 5 mm (SD 1.28), while in the BL values were 3.5 mm (SD 1.2) and 3.6 mm (SD 1.72), respectively. Addition of autogenous bone does not appear to statistically significantly enhance the results. Spontaneous membrane exposure occurred in 24% of the cases and was the only variant that significantly influenced results (P<0.001). CONCLUSIONS: Large vertical and/or horizontal ridge deficiencies may be treated with FDBA and ribose cross-linked collagen barrier membranes with good clinical outcome. No added effect of the application of a layer of autogenous bone in these bone augmentation procedures could be demonstrated. Spontaneous membrane exposure was the only parameter to affect the degree of new calcified tissue formation. PMID- 20572834 TI - Mandibular implant-supported overdentures and oral function. AB - OBJECTIVES: Oral rehabilitation by means of implant-retained mandibular overdentures is known to improve oral function. The aim of this study was to evaluate the long-term effects of mandibular implant treatment on oral function. We quantified maximum bite force and masticatory performance 10 years after implant treatment. It was hypothesized that these outcome measures would not change in this period. MATERIALS AND METHODS: Eighteen edentulous patients were scheduled for re-evaluation of their oral function 10 years after they had participated in a randomized cross-over clinical trial. In that trial, they had received two mandibular implants and a new denture with successively magnet-, ball-socket, and bar-clip attachments. RESULTS: At the 10-year follow-up, 14 of the initial 18 patients participated in the evaluation. As a result of the implant treatment, the average maximum bite force more than doubled, from 162 to 341 N, whereas the average number of chewing cycles to halve the initial particle size decreased from 55 to 27 cycles. No significant changes in maximum bite force and masticatory performance were observed after 10 years. However, the average maximum bite force obtained with implant-retained overdentures is still significantly lower than that of dentate subjects (569 N). CONCLUSION: Maximum bite force and masticatory performance significantly increased after implant treatment and remained unaltered during the following 10-year period. Thus, implant treatment greatly improves oral function for a long period of time. PMID- 20572836 TI - Availability of emergency dental treatment--a question of organization. PMID- 20572835 TI - Therapeutic management of post-kidney transplant hyperparathyroidism. AB - Left uncontrolled, persistent post-kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre-existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long-term uncontrolled HPT in post-kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy-associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post-kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non-surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post-kidney transplant HPT, associated complications, and current options for clinical management. PMID- 20572837 TI - Review of recommendations for the management of dental trauma presented in first aid textbooks and manuals. AB - BACKGROUND: To be able to help at the site of the oro-facial injury, the majority of persons would turn to medical books and first-aid books to extend their knowledge. Proper information in first-aid textbooks and manuals should be the best way to present necessary procedures on how to act at the site of injury. The objective of this review is to report the quality of the knowledge presented in first-aid books and manuals. METHODS: We carried out a review of first-aid international textbooks and manuals available in Medical University Libraries in Poland. The inclusion criteria were all manuals on first-aid that were written for medical staff and lay persons, and were published between 1969 and 2007. All texts were screened for dental trauma treatment recommendations. RESULTS: Our literature review has shown that among 45 first-aid textbooks and manuals only 19 mention procedures for use in case of dental trauma. Of those texts, only 13 detail the storage media for an avulsed tooth until replantation. CONCLUSIONS: Current, evidence-based, recommendations concerning first-aid procedures after dental trauma should be incorporated in forthcoming editions of first-aid textbooks and manuals. The guidance on procedures contained in reviewed texts is misleading. PMID- 20572838 TI - Geographic modelling of jaw fracture rates in Australia: a methodological model for healthcare planning. AB - BACKGROUND/AIM: While Australians are one of the healthiest populations in the world, inequalities in access to health care and health outcomes exist for Indigenous Australians and Australians living in rural or urban areas of the country. Hence, the purpose of this study was to develop an innovative methodological approach for predicting the incidence rates of jaw fractures and estimating the demand for oral health services within Australia. MATERIALS AND METHODS: Population data were obtained from the Australian Bureau of Statistics and was divided across Australia by statistical local area and related to a validated remoteness index. Every episode of discharge from all hospitals in Western Australia for the financial years 1999/2000 to 2004/2005 indicating a jaw fracture as the principle oral condition, as classified by the International Classification of Disease (ICD-10AM), was the inclusion criterion for the study. Hospitalization data were obtained from the Western Australian Hospital Morbidity Data System. RESULTS: The model estimated almost 10 times higher jaw fracture rates for Indigenous populations than their non-Indigenous counterparts. Moreover, incidence of jaw fractures was higher among Indigenous people living in rural and remote areas compared with their urban and semi-urban counterparts. In contrast, in the non-Indigenous population, higher rates of jaw fractures were estimated for urban and semi-urban inhabitants compared with their rural and remote counterparts. CONCLUSIONS: This geographic modelling technique could be improved by methodological refinements and further research. It will be useful in developing strategies for health management and reducing the burden of jaw fractures and the cost of treatment within Australia. This model will also have direct implications for strategic planning for prevention and management policies in Australia aimed at reducing the inequalities gap both in terms of geography as well as Aboriginality. PMID- 20572839 TI - Mechanism in favorable prognosis of pediatric condylar fractures managed by closed procedures: an experimental study in growing rats. AB - The purpose of this study was to investigate the underlying mechanism in favorable prognosis following pediatric condylar fractures managed by closed procedures. Seventy-five 1-month-old male Wistar rats were used in this experiment. Unilateral medially rotated condyle fracture in growing rats was adopted as the condyle fracture model to investigate the mechanism in favorable healing of pediatric condylar fractures. The entire fracture healing process was investigated. The rotated subcondylar fractures in young rats healed by means of callus formation, with simultaneous and prompt repositioning of the condyle. The positive outcome in these condyle fractures was also associated with active cell proliferation potential in the condyle, as well as the condyle's remodeling capability. The growth potential and remodeling capability of the condyle during the growing period might be the intrinsic factor for favorable healing following pediatric condylar fractures managed by closed procedures. PMID- 20572840 TI - Traumatic dental injuries--knowledge and awareness among present and prospective teachers in selected urban and rural areas of Norway. AB - AIM: to evaluate the knowledge and awareness of traumatic dental injuries (TDI) in children and adolescents among present and prospective teachers in selected parts of Norway. MATERIAL AND METHODS: This was a descriptive cross-sectional study among present and prospective teachers. It was based on a questionnaire about TDI in children and adolescents (7-15 years of age). The participants originated from two areas, one rural and one urban. The teacher trainee students were from classes focusing on sport and physical education. Chi-square tests were used for comparisons of groups of responders and relevant variables. RESULTS: A total of 143 individuals responded to the questionnaire (response rate 73.7%). Few respondents were aware of the existence of information about managing TDI at their respective schools. Only one responder (rural area) had had any education about TDI, although more than one-third of all the teachers had encountered TDI in school settings. Knowledge related to handling avulsed teeth was lower compared with handling crown fractures. Generally, the teachers had a higher level of knowledge related to the correct handling of TDI compared with the student group and they were also more confident in their respective decisions than the younger group. CONCLUSIONS: The findings revealed poor knowledge and awareness of TDI among present and prospective teachers in selected parts of Norway. PMID- 20572841 TI - Prevalence of dental trauma in Pan American games athletes. AB - The aim of this cross-sectional epidemiological survey was to assess the prevalence of dental trauma in athletes representing 42 countries competing at the most recent Pan American Games (XV Pan Am) held in Rio de Janeiro, Brazil in July of 2007, and to determine prior use and type of mouthguard among this group of athletes. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >5500 participating athletes competing in 41 sports and to the Medical Committee of the Pan American Sports Organization before and during the XV PAN. A convenience sample of 409 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded on a specific trauma form. The mean age of the athletes was 24.4 +/- 5.3 years. Males comprised 55% of the sample; females 45%. The prevalence of dental trauma among the athletes was 49.6% (n = 203) with no gender based differences. Most of these injuries (63.6%) were related to activities during training or competition. Sports with the highest injury prevalence were wrestling (83.3%), boxing (73.7%), basketball (70.6%) and karate (60%). The most common injury was enamel fracture (39.8%); root fracture was the least common (0.4%). The teeth most affected were the maxillary permanent central incisors (n = 113), followed by the mandibular central incisors (n = 19). Based on the results of this study, nearly one-half of the subjects had experienced previous dental trauma; the majority related to sports activities. Furthermore, only 17% of the athletes reported prior mouthguard use; the most frequent mouthguards reported were boil-and-bite. These results suggest the importance of enhanced educational efforts and the use of properly fitted mouthguards to reduce dental trauma among athletes in international sports competition, especially in sports where mouthguards are not mandatory. PMID- 20572842 TI - Dental injuries among children and adolescents aged 1-15 years attending to public hospital in Temuco, Chile. AB - A cross-sectional study was carried out in children and adolescents of both sexes, aged 1-15 years that sought dental emergency attention to the Regional Hospital between 2004 and 2007 in Temuco, Chile. The purpose of this study was to identify the aetiology, types of traumatic dental injuries in primary and permanent dentitions, sex and age distributions, accident location; and time elapsed before emergency treatment in children and adolescents. The sample consisted of 359 patients with 145 primary teeth and 525 permanent teeth affected by dental trauma. The results showed a 2:1 male:female ratio distribution (242/117) with a mean age of 8.4 years. The 7- to 12-year-old group had the highest frequency of dental injuries (66.6%). Unspecific accidental falls were the main cause of injury to primary and permanent dentition (51.8%), followed by striking teeth against objects (15.6%) and bike accidents (13.9%). In primary dentition the most common diagnosis were subluxation (38.6%) and avulsion (16.6%), whereas in permanent dentition was uncomplicated crown fracture (32.9%). A high proportion of the patients received their first emergency attention 24 h after the accident (32.6%). This study revealed a high frequency (37.9%) in 1-15 aged population that sought emergency attention by dental trauma in the period of time study. A large proportion of children with dental trauma received delayed first emergency care, even 24 h after the accident. Considering the high frequency of traumatic dental injuries in 1-15 aged population and the high percentage of delayed emergency attention is necessary to develop effective educational campaigns in regard to causes, prevention and emergency management of traumatic dental injuries, especially in deprived areas. In conclusion, traumatic dental injury may be considered as a serious dental public health problem especially in children of deprived areas. PMID- 20572843 TI - Effect of temperature and storage media on human periodontal ligament fibroblast viability. AB - Many solutions have been examined as possible storage media for avulsed teeth. The purpose of this study was to compare the effectiveness of several storage media to preserve cultured periodontal ligament fibroblasts (PDLF) under different temperatures. The media tested were: sterile Hank's balanced salt solution (sHBSS), non-sterile HBSS (nHBSS), skimmed milk, Save-A-Tooth((R)), Minimum Essential Medium (MEM) and water (negative control). MEM at 37 degrees C was used as positive control. PDLF were obtained from explants of extracted healthy human teeth. Plates containing confluent PDLF were soaked in the various media for 3, 6, 24, 48 and 72 h at 37 degrees C and 20 degrees C. After incubation, viability of the cells was determined using the tetrazolium salt based colorimetric (MTT) assay and the Trypan Blue exclusion test after 6, 24, 48 and 72 h of incubation at 20 degrees C. The results were analyzed statistically using Kruskal-Wallis, Scheffe and Mann-Whitney (alpha = 5%) tests. Results from the MTT assay at 37 degrees C and 20 degrees C showed that skimmed milk was the best storage medium for up to 24 and 48 h, respectively, followed by nHBSS and sHBSS. Results from the Trypan Blue exclusion test showed that the best storage media were milk, sHBSS and nHBSS, with no statistical differences, for any time period. The Save-A-Tooth((R)) had a detrimental effect on cells after 24 h. The influence of temperature on the effectiveness of the storage media tested showed at 20 degrees C a decreasing order of efficacy as follows: milk > sHBSS and nHBSS > MEM > Save-A-Tooth((R)) > water while at 37 degrees C it was: MEM > nHBSS > milk > sHBSS > Save-A-Tooth((R)) > water. In conclusion, incubation temperature altered the effectiveness of the storage media and skimmed milk at 20 degrees C was better than HBSS in maintaining PDLF viability. PMID- 20572844 TI - Knowledge of emergency management of avulsed teeth: a survey of dentists in Beijing, China. AB - OBJECTIVES: There is a high frequency of dental trauma cases in China, where tooth avulsion is one of the most serious scenarios. The knowledge of how to take care of an avulsion is of great importance to the outcome of such an injury. This knowledge among dentists in Beijing, China has never been tested before. The purpose of this study was to evaluate professional experience and knowledge of emergency management of dentists working in urban and suburban areas of Beijing, China. MATERIAL AND METHODS: A two-part questionnaire was distributed to 175 urban and 99 suburban dentists in Beijing. The first part contained personal and professional information of the participating dentists. The second part evaluated dentists' knowledge about the emergency management of avulsed teeth. Data were entered into a SPSS database and analyzed using the chi-square test and Fisher's exact test for each question. RESULTS: All dentists had a college or above degree. Almost five times as many urban dentists compared to suburban dentists presented with a Master or PhD degree. The knowledge levels of the participants presenting with correct answer in the respective knowledge areas were; storage medium (15.8%) intra-canal medication (45.0%), type of splint (45.1%) and splinting period (10.2%). Significantly more urban dentists (50.6%) compared to suburban dentists (34.8%) (P = 0.016), used calcium hydroxide paste as an intracanal medicament, and significantly more urban dentists (51.3%) than suburban dentists (34.1%) chosed a flexible splint (P = 0.008). CONCLUSION: The results revealed an uneven pattern of knowledge between urban and suburban dentists regarding the emergency management of avulsed teeth. The study highlighted Chinese dentists' need for continuing education in order to improve current knowledge in emergency management of avulsed teeth. PMID- 20572845 TI - Miniscrew-anchored alveolar distraction for the treatment of the ankylosed maxillary central incisor. AB - This report presents the case of a 20-year-old female patient exhibiting an infraoccluded ankylosed maxillary central incisor that was avulsed and replanted after traumatic injury during childhood. To reposition the osseous and gingival margins of the ankylosed tooth to an ideal level, a new alveolar distraction device that uses anchoring miniscrews with a single tooth dento-osseous osteotomy was fabricated and the ankylosed tooth was successfully treated with exceptional patient compliance. PMID- 20572846 TI - Trauma-induced dentigerous cyst involving an inverted impacted mesiodens: case report. AB - There have been only a small number of studies on the association of dentigerous cysts with supernumerary teeth. The purpose of this article was to report the case of a dentigerous cyst associated with an impacted inverted mesiodens that developed secondary to trauma to its predecessor, a non-vital permanent maxillary central incisor. As a consequence of trauma, the central incisor's root development was prematurely arrested and the open apex lay close to the follicle of the underlying inverted mesiodens. The negligent attitude of both the child and parent in seeking dental treatment was a contributing factor. The case was further complicated by impaction of the adjacent permanent central incisor due to the presence of another unerupted but normally oriented mesiodens. Occlusal and Intraoral periapical radiographs revealed a well-defined radiolucent area surrounding the inverted mesiodens. Microscopic examination revealed a cystic cavity that was lined by 2-3 cell thick non-keratinized stratified squamous epithelium resembling reduced enamel epithelium. Dentigerous cysts associated with impacted permanent teeth are not uncommon but the cysts which are induced by trauma are uncommon. Development of trauma-induced dentigerous cyst around an inverted impacted mesiodens associated with the periapical area of a traumatized, non-vital, immature permanent central incisor is a rare occurrence. PMID- 20572847 TI - Use of topical as only anesthetic for suturing a traumatic facial laceration. AB - A case is described where only topical anesthetic was used for suturing facial lacerations. The patient had sustained facial lacerations after a motor vehicle accident. After some initial treatment the patient refused injection anesthesia so only topical anesthetics lidocaine-prilocaine was used for one of the lacerations. Suturing was possible to perform with only topical anesthesia with good patient comfort. PMID- 20572848 TI - Routine systemic antibiotic prescription in the management of permanent avulsed teeth--should we stop? PMID- 20572849 TI - Comments on routine systemic antibiotic prescription in the management of permanent avulsed teeth. PMID- 20572850 TI - Long-term effects of Hurricane Katrina on the psychological well-being of evacuees. AB - Hurricane Katrina of August 2005 forced more than one million people to evacuate the Gulf Coast of the United States. This study examines the psychological health and well-being of a subset of evacuees to determine the prevalence of ongoing mental health problems. Interviews were conducted with 101 adults who evacuated to Louisville, Kentucky, and were living in the state at the one-year anniversary of the event or had recently returned to the Gulf Coast. The psychological health and well-being of respondents was evaluated using several well-validated measures. More than one-half met the criteria for post-traumatic stress disorder and a majority were suffering from depression and anxiety. The mean quality of life score was 0.6 on a scale from 0-1, suggesting that adaptation and return to pre-hurricane well-being had not occurred 12 months after the storm. The potential for long-term psychological damage exists in this sample of Hurricane Katrina evacuees. Results suggest other evacuees may also be at heightened risk. PMID- 20572851 TI - Timing crisis information release via television. AB - When and how often to release information on television are important issues in crisis and emergency risk communication. There is a lot of crisis information, including warnings and news, to which people should have access, but most of it is not significantly urgent to interrupt the broadcasting of television programmes. Hence, the right timing for the release of crisis information should be selected based on the importance of the crisis and any associated communication requirements. Using recursive methods, this paper builds an audience coverage model of crisis information release. Based on 2007 Household Using TV (HUT) data for Hefei City, China, the optimal combination of broadcasting sequence (with frequencies between one and eight times) is obtained using the implicit enumeration method. The developed model is applicable to effective transmission of crisis information, with the aim of reducing interference with the normal television transmission process and decreasing the psychological effect on audiences. The same model can be employed for other purposes, such as news coverage and weather and road information. PMID- 20572852 TI - Regional myocardial function in children with chronic aortic regurgitation. AB - AIM: To determine the influence of volume overload on regional myocardial function in children with aortic regurgitation (AR) using tissue Doppler echocardiography and strain rate imaging (TDE/SRI). METHODS: Thirty children with AR (median age 14 years (range 3-28 years)) were divided into three groups: mild (n = 6), moderate (n = 15), and severe AR (n = 9). Patients and 30 matched healthy controls underwent echocardiography with TDE/SRI. Cineloops were acquired from parasternal long- and short-axis and from apical four- and two-chamber views. The following parameters were extracted: peak systolic (V(S) ) and diastolic (V(E) ) velocities, peak systolic strain (S), peak systolic (SR(S) ), and early diastolic strain rate (SR(E) ). To quantify longitudinal LV function, V(S) and V(E) were obtained as peak values in the basal segments, whereas S, SR(S) , and SR(E) were expressed as mean values between basal and midwall segments. RESULTS: Compared to the control group, patients showed a significant reduction in V(E) in the longitudinal direction (-91 +/- 30 mm/sec for patients vs. 119 +/- 20 mm/sec for control group). In patients with severe AR, longitudinal SR(E) was significantly reduced. On the other hand, we noted no differences between patients and controls with regard to S and SR(S) values. CONCLUSION: Children with AR presented with significantly reduced longitudinal diastolic function (V(E) ). Severe AR leads to a decrease in diastolic myocardial deformation (SR(E) ). Due to the short duration of AR in this group of patients, systolic function (SR(S) ) is still preserved. PMID- 20572853 TI - CME: long-term outcome in asymptomatic patients with severe aortic regurgitation, normal left ventricular ejection fraction, and severe left ventricular dilatation. AB - BACKGROUND: Although the guidelines consider severe left ventricular (LV) dilatation a class IIaC indication for surgery in asymptomatic patients with severe aortic regurgitation (AR) and normal LV function, the optimal management remains controversial. We aimed to assess the LV enlargement, hypertrophy and function, and the outcomes in these patients by the presence of severe LV dilatation at baseline. METHODS: From our 20-year database, we identified all asymptomatic patients with severe AR and LV ejection fraction (EF) >50% and >=2 echocardiograms >=1 year apart. LV end-diastolic diameter >70 mm or LV end systolic diameter >50 mm or LV end-systolic diameter index >25 mm/m(2) defined severe LV dilatation. A composite end point included onset of symptoms or LV dysfunction. RESULTS: Eighty-four patients (52 +/- 18 years, 61 men) were enrolled and followed-up for 7.1 +/- 5.1 years. Two groups were defined: 22 patients with and 62 patients without severe LV dilatation at baseline. The progression of LV dilatation and hypertrophy, and the LVEF at last exam were similar in both groups. Twelve of 22 and 34 of 62 patients (P = 0.59) reached the end point. Vasodilators did not modify the progression of LV enlargement/hypertrophy. Ten of 22 and 25 of 62 patients (P = 0.45) underwent surgery and had similar postoperative LV diameters, mass, EF. CONCLUSIONS: The progression of LV enlargement/hypertrophy and outcomes in asymptomatic patients with severe AR, normal LV function, and severe LV dilatation or the postoperative LV parameters were not influenced by the severe LV dilatation, suggesting that a close follow-up could delay surgery in this population. PMID- 20572854 TI - MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate. AB - Recent studies suggest that multiple interacting loci, with possible additional environmental factors, influence the risk for nonsyndromic oral clefts, one of the most common birth defects in humans. Advances in high-throughput genotyping technology allow the testing of multiple markers, simultaneously, in many candidate genes. We tested for associations between 176 haplotype-tagging single nucleotide polymorphisms (SNPs) in 18 candidate genes/loci and nonsyndromic clefts in a case-control study in an Estonian sample (153 patients, 205 controls). The most significant associations with nonsyndromic cleft lip with or without cleft palate (CL/P) were found for SNPs in MSX1, MTHFR, and PVRL2, including several common haplotypes in the MTHFR and MSX1 genes. The strongest association was observed for rs6446693 in the MSX1 region, which remained statistically significant after Bonferroni correction. The strongest association with nonsyndromic cleft palate (CP) was found for the SNP rs11624283 in the JAG2 gene. Epistatic interactions were observed for SNPs within PVRL2, between BCL3 and EDN1, and between IRF6 and MSX1 genes. This study provides further evidence implicating MSX1 and MTHFR in the etiology of nonsyndromic CL/P across different populations. PMID- 20572855 TI - Developmental changes in cellular and extracellular structural macromolecules in the secondary palate and in the nasal cavity of the mouse. AB - The aim of this study was to analyse the hitherto largely unknown expression patterns of some specific cellular and extracellular molecules during palate and nasal cavity development. We showed that epithelia of the developing palate and the vomerine epithelium express similar sets of structural proteins. With the exception of keratin 15, which becomes barely detectable in the elevated palatal shelves, nearly all of these proteins become upregulated at the presumptive areas of fusion and in the adhering epithelia of the palate and nasal septum. In vivo and in vitro analyses indicated that reduction in the amount of keratin 15 protein is independent of Tgfbeta-Alk5 signalling. Foxa1 expression also highlighted the regionalization of the palatal and nasal epithelia. Owing to the lack of reliable markers of the palatal periderm, the fate of peridermal cells has been controversial. We identified LewisX/stage-specific embryonic antigen-1 as a specific peridermal marker, and showed that numerous peridermal cells remain trapped in the medial epithelial seam (MES). The fate of these cells is probably apoptosis together with the rest of the MES cells, as we provided strong evidence for this event. Heparan sulphate, chondroitin-6-sulphate, and versican displayed dynamically changing distribution patterns. The hitherto-unknown innervation pattern of the developing palate was revealed. These findings may be of value for unravelling the pathogenesis of palatal clefting. PMID- 20572856 TI - Intracellular Ca2+ responses and cell volume regulation upon cholinergic and purinergic stimulation in an immortalized salivary cell line. AB - The water channel aquaporin 5 (AQP5) seems to play a key role in salivary fluid secretion and appears to be critical in the cell volume regulation of acinar cells. Recently, the cation channel transient potential vanilloid receptor 4 (TRPV4) was shown to be functionally connected to AQP5 and also to cell volume regulation in salivary glands. We used the Simian virus 40 (SV40) immortalized cell line SMG C10 from the rat submandibular salivary gland to investigate the effect of ATP and the neurotransmitter analogue carbachol on Ca(2+) signalling and cell volume regulation, as well as the involvement of TRPV4 in the responses. We used fura-2-AM imaging, cell volume measurements, and western blotting. Both carbachol and ATP increased the concentration of intracellular Ca(2+), but no volume changes could be measured. Inhibition of TRPV4 with ruthenium red impaired both ATP- and carbachol-stimulated Ca(2+) signals. Peak Ca(2+) signalling during hyposmotic exposure was significantly decreased following inhibition of TRPV4, while the cells' ability to volume regulate appeared to be unaffected. These results show that in the SMG C10 cells, simulation of nervous stimulation did not induce cell swelling, although the cells had intact volume regulatory mechanisms. Furthermore, even though Ca(2+) signals were not needed for this volume regulation, TRPV4 seems to play a role during ATP and carbachol stimulation. PMID- 20572857 TI - Protein and mucin retention on oral mucosal surfaces in dry mouth patients. AB - Oral homeostasis depends largely on proteins and mucins present in saliva that coat all oral surfaces. The present study compared the protein composition of residual fluid on mucosal surfaces in subjects with normal salivary flow with that of patients with dry mouth caused by salivary hypofunction. Samples of residual mucosal fluid were collected using paper strips and then analysed by protein electrophoresis and immunoblotting. In both patients and controls, residual fluids on mucosal surfaces (except the anterior tongue in control subjects) had higher protein concentrations than unstimulated whole-mouth saliva. High-molecular-weight mucin (MUC5B) was present in greater amounts on the anterior tongue than on other surfaces in control subjects. In dry mouth patients who were unable to provide a measurable saliva sample, MUC5B was often still present on all mucosal surfaces but in reduced amounts on the anterior tongue. The membrane-bound mucin, MUC1, was prominent on buccal and labial surfaces in patients and controls. Statherin was still present on surfaces that were dried to remove salivary fluid, suggesting that it may be adsorbed as a protein pellicle. It is concluded that oral mucosal surfaces in dry mouth patients can retain MUC5B and other salivary proteins, although the functional integrity of these proteins is uncertain. PMID- 20572858 TI - Can parents and children evaluate each other's dental fear? AB - The aim of this study was to determine whether parents and their 11-16-yr-old children can evaluate each other's dental fear. At baseline the participants were 11-12-yr-old children from the Finnish Cities of Pori (n = 1,691) and Rauma (n = 807), and one of their parents. The children and their parents were asked if they or their family members were afraid of dental care. Fears were assessed using single 5-point Likert-scale questions that included a 'do not know' option. Children and parents answered the questionnaire independently of each other. Background variables were the child's and their parent's gender. Parents' and children's knowledge of each other's dental fear was evaluated with kappa statistics and with sensitivity and specificity statistics using dichotomized fear variables. All kappa values were < 0.42. When dental fear among children and parents was evaluated, all sensitivities varied between 0.10 and 0.39, and all specificities varied between 0.93 and 0.99. Evaluating dental fear among fearful children and parents, the sensitivities varied between 0.17 and 0.50 and the specificities varied between 0.85 and 0.94, respectively. Parents and children could not recognize each other's dental fear. Therefore, parents and children cannot be used as reliable proxies for determining each other's dental fear. PMID- 20572859 TI - Towards a better understanding of dental anxiety and fear: cognitions vs. experiences. AB - Traumatic dental experiences are associated with dental anxiety and fear. However, many people with no dental fear have had negative dental experiences, and some people with considerable fear fail to recall any traumatic incidents. This study aimed to determine whether dental fear was better explained by experiences or by cognitive perceptions of going to the dentist as being uncontrollable, unpredictable, dangerous, and disgusting. A random sample of 1,084 Australian adults (response rate = 71.7%) completed a mailed questionnaire with measures of dental fear, perceptions of going to the dentist, and dental experiences. Perceptions of uncontrollability, unpredictability, dangerousness, and disgustingness had strong bivariate associations with scores on the Index of Dental Anxiety and Fear (IDAF-4C). Vulnerability-related perceptions accounted for 46.3% of the variance in IDAF-4C scores beyond that accounted for by demographic variables and five possible dental experiences comprising intense pain, considerable discomfort, gagging, fainting, and having a personal problem with the dentist. In contrast, dental experiences accounted for < 1% of the variance in IDAF-4C scores beyond that accounted for by the four cognitive perceptions. Perceptions of uncontrollability, unpredictability, dangerousness, and disgustingness were superior predictors of dental fear compared with negative dental experiences. PMID- 20572860 TI - Post-trial costs, clinical outcomes, and dental service utilization after a randomized clinical trial for caries control among Finnish adolescents. AB - The aim of this study was to assess post-trial treatment costs, clinical outcomes [decayed, missing or filled surfaces (DMFS) scores], and utilization of dental services among adolescents who had participated in a randomized clinical trial (RCT) in Pori, Finland, in 2001-2005. At baseline the children were 11-12 yr of age and had had at least one active initial caries lesion. The children in the experimental group (n = 250) had been exposed to multiple measures for caries control, while those in the control group (n = 247) had received standard dental care. During the post-trial period (2005-2008), all participants received the standard dental care offered in public dental clinics in Pori. In both groups the costs of treatment procedures and outcomes for the post-trial period were calculated for each adolescent. Information from patient records was available for 487 adolescents (former experimental n = 246, control n = 241). The mean total costs per adolescent were lower and the clinical outcome was better among the former experimental-group participants. The differences in mean costs between the groups were statistically significant for preventive and restorative procedures. The utilization of dental services was significantly more regular among the former experimental-group participants. PMID- 20572861 TI - Possible predictors of discontinuation of specialized dental treatment among children and adolescents with dental behaviour management problems. AB - This study aimed to identify potential predictors of non-attendance among children and adolescents with dental behaviour management problems (DBMP). A group of 179 patients, 7.5-19 yr of age, was grouped into 56 'non-attenders' (discontinued treatment, missed appointments, or >or= 20% cancellations) and 123 'attenders'. In addition to data from an introductory interview and dental recordings, baseline data from psychometric measures of fear and other personal and parental characteristics were included in logistic regression analyses and tree-based modelling. The non-attenders had higher scores on impulsivity and sociability and lower socio-economic status (SES) than the attenders, and they lived more often in single-parent families. Logistic regression analyses and tree based modelling point to SES and parental anxiety as important predictors for non attendance within this group of children and adolescents. To predict, and possibly to prevent, non-attendance among children and adolescents referred for specialized dental care because of DBMP, we must consider their lives and family situations as well as their personal characteristics and oral health status. Further research should focus on whether the observed associations between non attendance and factors such as personal characteristics, family and psychosocial factors, and previous dental experiences, also hold for those who remain in regular dental care. PMID- 20572862 TI - Rasch analysis of the Geriatric Oral Health Assessment Index. AB - The aim of this study was to perform a psychometric analysis on the Geriatric Oral Health Assessment Index (GOHAI) using Rasch analysis, a modern statistical approach for examining rating scale data. Eighty-five subjects, long-term residents of a nursing home, were analysed using the GOHAI. The mean GOHAI score (range 0-48) was 11. Two of the five rating categories (1 = seldom; 3 = often) did not comply with the Rasch criteria for category functioning. After collapsing rating categories into a three-level rating scale (0 = never; 1 = sometimes; 2 = often/always), the new model met the set criteria. Item 12 'sensitivity to hot, cold or sweets' was misfitting. Rasch analysis showed both the unidimensionality of (at least) 11 of the 12 items of GOHAI, and the possibility of simplifying the structure of its rating scale. PMID- 20572863 TI - Changes in toothbrushing frequency in relation to changes in oral health-related knowledge and attitudes among children - a longitudinal study. AB - The aim of this study was to determine the associations between changes in self reported toothbrushing frequency and the knowledge and attitudes related to oral health. The study population consisted of all fifth and sixth graders who started the 2001-2002 school year in Pori (n = 1,691); of these, 1,362 were monitored throughout the 3.4-yr study. Data were gathered by questionnaires before, in the middle, and after the follow-up, which was divided into two periods. Associations between changes in toothbrushing frequency, sum score of knowledge items, and sum scores of items in attitudinal factors were studied. The attitudinal factor structure was determined by principal component analyses. The associations were evaluated using mean values and general linear models for repeated measures. Toothbrushing frequency and knowledge and attitudes related to oral health improved among the same children during the study, with the changes usually taking place in the same time-period. In different time-periods, different children's toothbrushing and oral health-related knowledge and attitudes improved. Based on our results, changes in knowledge, attitudes, and behavior are related, but children are ready for change at different times. Therefore, oral health promotion should be designed to be a continuous process rather than a short-term intervention. PMID- 20572864 TI - Treatment of deep caries lesions in adults: randomized clinical trials comparing stepwise vs. direct complete excavation, and direct pulp capping vs. partial pulpotomy. AB - Less invasive excavation methods have been suggested for deep caries lesions. We tested the effects of stepwise vs. direct complete excavation, 1 yr after the procedure had been carried out, in 314 adults (from six centres) who had received treatment of a tooth with deep caries. The teeth had caries lesions involving 75% or more of the dentin and were centrally randomized to stepwise or direct complete excavation. Stepwise excavation resulted in fewer pulp exposures compared with direct complete excavation [difference: 11.4%, 95% confidence interval (CI) (1.2; 21.3)]. At 1 yr of follow-up, there was a statistically significantly higher success rate with stepwise excavation, with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [difference: 11.7%, 95% CI (0.5; 22.5)]. In a subsequent nested trial, 58 patients with exposed pulps were randomized to direct capping or partial pulpotomy. We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [31.8% and 34.5%; difference: 2.7%, 95% CI (-22.7; 26.6)]. In conclusion, stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation. In view of the poor prognosis of vital pulp treatment, a stepwise excavation approach for managing deep caries lesions is recommended. PMID- 20572865 TI - Caries outcomes after orthodontic treatment with fixed appliances: do lingual brackets make a difference? AB - Orthodontic treatment with fixed appliances is considered a risk factor for the development of white spot caries lesions (WSL). Traditionally, brackets are bonded to the buccal surfaces. Lingual brackets are developing rapidly and have become more readily available. Buccal surfaces are considered to be more caries prone than lingual surfaces. Furthermore, lingual brackets are shaped to fit the morphology of the teeth and seal almost the entire surface. In the present study we tested the hypothesis that lingual brackets result in a lower caries incidence than buccal brackets. We tested this hypothesis using a split-mouth design where subjects were allocated randomly to a group receiving either buccal or lingual brackets on the maxillary teeth and the alternative bracket type in the mandible. The results indicate that buccal surfaces are more prone to WSL development, especially when WSL existed before treatment. The number of WSL that developed or progressed on buccal surfaces was 4.8 times higher than the number of WSL that developed or progressed on lingual surfaces. When measured using quantitative light-induced fluorescence (QLF), the increase in integrated fluorescence loss was 10.6 times higher buccally than lingually. We conclude that lingual brackets make a difference when caries lesion incidence is concerned. PMID- 20572866 TI - The effect of ageing on the elastic modulus and degree of conversion of two multistep adhesive systems. AB - During the curing reaction, the monomers of dentine bonding systems should cross link sufficiently to strengthen an adhesive so that it is clinically reliable. This study evaluated how different storage conditions (air vs. water storage) affect the elastic modulus (E-modulus) and degree of conversion (DC) of a three step etch-and-rinse adhesive and a two-step self-etch adhesive. The biaxial flexural test and Raman microscopy were performed on resin disks made from the bonding agents Adper Scotchbond Multi-Purpose (SBMP; 3M ESPE) and Clearfil Protect Bond (CPB; Kuraray). The measurements were repeated after storage in either air or water for 15 and 30 min and for 1, 24, and 72 h. At time 0, the E modulus was not affected by the adhesive system, whilst the degree of cure of CPB was higher than that of SBMP. Air storage increased the E-modulus at each ageing interval. Storage in water increased the E-modulus until it reached a maximum at 24 h, after which it decreased significantly at 72 h. No linear correlation between the percentage DC and E-modulus of the two adhesives was found when stored in water. The results of this study indicate that the mechanical properties and polymerization kinetics of SBMP and CPB are affected by storage time and medium. PMID- 20572867 TI - Metameric effect between natural teeth and the shade tabs of a shade guide. AB - The objective of this study was to evaluate metameric effects, that is, the dependence of the colours of teeth and shade tabs on the illuminant used. The colours of 49 teeth of 37 participants and of the corresponding shade tabs of the 3D-Master (VITA Zahnfabrik; colour match DeltaE(ab)< 2) were measured using an intra-oral spectrophotometer (VITA Easyshade). Spectral reflectance data (from 400 to 700 nm) were recorded. Commission Internationale de l'Eclairage (CIE) L*a*b* values were calculated for D65 (reference daylight), A (incandescent light), and TL84 (store/office light) as reference illuminants. A modified metamerism index (Mod-M) and hue-angle ratios were calculated to express differences between tooth and tab colour relative to the difference observed under D65 illumination. The Mod-M for teeth and tabs was greater than unity (indicating a greater colour difference relative to D65) by 57.1% for A and by 49.3% for TL84. Hue-angle ratios of teeth and tabs using the test illuminants were different from those obtained using the standard illuminant D65. If teeth and shade tab matching is conducted using daylight illumination, the colour difference may not be the same under other lighting conditions, leading to perceptible, or even unacceptable, colour differences under these conditions. PMID- 20572868 TI - Susceptibility locus for non-syndromic cleft lip with or without cleft palate on chromosome 10q25 confers risk in Estonian patients. AB - Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects and has a multifactorial etiology that includes both genetic and environmental factors. Recently, two novel susceptibility loci and three suggestive loci for NSCL/P were identified by a genome-wide association scan (GWAS) in a German population with subsequent independent replication in a mixed European population. The aim of the present study was to investigate whether these newly detected loci confer similar effects in the North-East European Baltic population. A total of 101 NSCL/P patients and 254 controls from Estonia were included. A significant association was observed for rs7078160 (P = 0.0016) at chromosome 10q25, which confirms the association of this locus with NSCL/P in the Baltic population. No significant association was found for the other four loci, a result that may have been attributable to the limited power of the sample. PMID- 20572869 TI - Mechanisms of stationary-phase mutagenesis in bacteria: mutational processes in pseudomonads. AB - In a growth-restricting environment, mutants arise that are able to take over bacterial populations by a process known as adaptive mutation or stationary-phase mutation. This process is best studied in Escherichia coli. The genus Pseudomonas represents one of the largest groups of bacteria able to colonize multiple habitats and to adapt rapidly to new environments. The majority of bacteria including pseudomonads contain a different set of DNA polymerases and DNA repair enzymes than those identified in E. coli. The aim of this review is to provide an overview of the results of studies of mutagenic processes in pseudomonads and to discuss these results in the light of the mechanisms of stationary-phase mutagenesis discovered in E. coli. PMID- 20572870 TI - Mucilaginibacter dorajii sp. nov., isolated from the rhizosphere of Platycodon grandiflorum. AB - A Gram-negative, nonmotile and rod-shaped bacterial strain was isolated from the rhizosphere of Platycodon grandiflorum in a study of bacterial diversity, and its taxonomic position was investigated by a genotypic and phenotypic analysis. This isolate, designated as DR-f4, grew at 4-30 degrees C (optimally at 20-25 degrees C) and in the presence of 0-1% (w/v) NaCl. It contained MK-7 as the predominant menaquinone. The isolate had activities of catalase, oxidase and beta galactosidase and hydrolyzed aesculin, casein, carboxymethyl-cellulose, starch and L-tyrosine. The major cellular fatty acids were summed feature 3 (C(16:1)omega7c and/or iso-C(15:0) 2OH) and iso-C(15:0). The DNA G+C content was 42.6 mol%. This isolate belonged to the genus Mucilaginibacter based on phylogenetic analysis using 16S rRNA gene sequences. The nearest phylogenetic neighbors of strain DR-f4(T) were Mucilaginibacter lappiensis ANJL12(T) and Mucilaginibacter rigui WPCB133(T), with 16S rRNA gene sequence similarity levels of 96.9% and 96.4%, respectively. The genotypic and phenotypic evidence suggests that strain DR-f4(T) should be classified as a novel species, for which the name Mucilaginibacter dorajii sp. nov. is proposed. The type strain for the novel species is DR-f4(T) (=KACC 14556(T)=JCM 16601(T)). PMID- 20572871 TI - Kinetics and redox regulation of Gpx1, an atypical 2-Cys peroxiredoxin, in Saccharomyces cerevisiae. AB - The budding yeast Saccharomyces cerevisiae has three homologues of glutathione peroxidase (GPX1, GPX2, and GPX3). Two structural homologues of the mammalian glutathione peroxidase, Gpx2 and Gpx3, have been proven to be atypical 2-Cys peroxiredoxins, which prefer to use thioredoxin as an electron donor. Here, we show that Gpx1 is also an atypical 2-Cys peroxiredoxin, but uses glutathione and thioredoxin almost equally. We determined the redox state of Gpx1 in vivo. PMID- 20572872 TI - Serpentinization as a source of energy at the origin of life. AB - For life to have emerged from CO2, rocks, and water on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, minor formate, and ammonia, as well as calcium and traces of acetate, molybdenum and tungsten, to off-ridge alkaline hydrothermal springs that interfaced with the metal-rich carbonic Hadean Ocean. Silica and bisulfide were also delivered to these springs where cherts and sulfides were intersected by the alkaline solutions. The proton and redox gradients so generated represent a rich source of naturally produced chemiosmotic energy, stemming from geochemistry that merely had to be tapped, rather than induced, by the earliest biochemical systems. Hydrothermal mounds accumulating at similar sites in today's oceans offer conceptual and experimental models for the chemistry germane to the emergence of life, although the ubiquity of microbial communities at such sites in addition to our oxygenated atmosphere preclude an exact analogy. PMID- 20572873 TI - Simulation and analysis of conjunctive use with MODFLOW's farm process. AB - The extension of MODFLOW onto the landscape with the Farm Process (MF-FMP) facilitates fully coupled simulation of the use and movement of water from precipitation, streamflow and runoff, groundwater flow, and consumption by natural and agricultural vegetation throughout the hydrologic system at all times. This allows for more complete analysis of conjunctive use water-resource systems than previously possible with MODFLOW by combining relevant aspects of the landscape with the groundwater and surface water components. This analysis is accomplished using distributed cell-by-cell supply-constrained and demand-driven components across the landscape within "water-balance subregions" comprised of one or more model cells that can represent a single farm, a group of farms, or other hydrologic or geopolitical entities. Simulation of micro-agriculture in the Pajaro Valley and macro-agriculture in the Central Valley are used to demonstrate the utility of MF-FMP. For Pajaro Valley, the simulation of an aquifer storage and recovery system and related coastal water distribution system to supplant coastal pumpage was analyzed subject to climate variations and additional supplemental sources such as local runoff. For the Central Valley, analysis of conjunctive use from different hydrologic settings of northern and southern subregions shows how and when precipitation, surface water, and groundwater are important to conjunctive use. The examples show that through MF-FMP's ability to simulate natural and anthropogenic components of the hydrologic cycle, the distribution and dynamics of supply and demand can be analyzed, understood, and managed. This analysis of conjunctive use would be difficult without embedding them in the simulation and are difficult to estimate a priori. PMID- 20572874 TI - Solutions for non-Darcian flow to an extended well in fractured rock. AB - We have investigated non-Darcian flow to a vertical fracture represented as an extended well using a linearization procedure and a finite difference method in this study. Approximate analytical solutions have been obtained with and without the consideration of fracture storage based on the linearization procedure. A numerical solution for such a non-Darcian flow case has also been obtained with a finite difference method. We have compared the numerical solution with the approximate analytical solutions obtained by the linearization method and the Boltzmann transform. The results indicate that the linearized solution agrees generally well with the numerical solution at late times, and underestimates the dimensionless drawdown at early times, no matter if the fracture storage is considered or not. When the fracture storage is excluded, the Boltzmann transform solution overestimates the dimensionless drawdown during the entire pumping period. The dimensionless drawdowns in the fracture with fracture storage for different values of dimensionless non-Darcian hydraulic conductivity beta approach the same asymptotic value at early times. A larger beta value results in a smaller dimensionless drawdown in both the fracture and the aquifer when the fracture storage is included. The dimensionless drawdown is approximately proportional to the square root of the dimensionless time at late times. PMID- 20572875 TI - An analytical model for hydraulic fracturing in shallow bedrock formations. AB - A theoretical method is proposed to estimate post-fracturing fracture size and transmissivity, and as a test of the methodology, data collected from two wells were used for verification. This method can be employed before hydrofracturing in order to obtain estimates of the potential hydraulic benefits of hydraulic fracturing. Five different pumping test analysis methods were used to evaluate the well hydraulic data. The most effective methods were the Papadopulos-Cooper model (1967), which includes wellbore storage effects, and the Gringarten-Ramey model (1974), known as the single horizontal fracture model. The hydraulic parameters resulting from fitting these models to the field data revealed that as a result of hydraulic fracturing, the transmissivity increased more than 46 times in one well and increased 285 times in the other well. The model developed by dos Santos (2008), which considers horizontal radial fracture propagation from the hydraulically fractured well, was used to estimate potential fracture geometry after hydrofracturing. For the two studied wells, their fractures could have propagated to distances of almost 175 m or more and developed maximum apertures of about 2.20 mm and hydraulic apertures close to 0.30 mm. Fracturing at this site appears to have expanded and propagated existing fractures and not created new fractures. Hydraulic apertures calculated from pumping test analyses closely matched the results obtained from the hydraulic fracturing model. As a result of this model, post-fracturing geometry and resulting post-fracturing well yield can be estimated before the actual hydrofracturing. PMID- 20572876 TI - Spontaneous carotidynia. PMID- 20572877 TI - Thunderclap headache. PMID- 20572878 TI - Migraine in the pediatric population--evolving concepts. AB - Studying the prevalence of headaches at age extremes is of important clinical relevance. Pediatric studies inform us about determinants of incident disease; studies of elderly populations inform us about the long-term consequences of headaches, as well as about determinants of headache remission. As with other subspecialties of headache research, research on pediatric headache is an evolving field. However, although substantial advances have been achieved in understanding headaches in adolescents, knowledge of early childhood headaches is not as advanced conceptually. This review provides a theoretical framework for our current understanding, then summarize the results of a large, ongoing, epidemiological study in pre-adolescent children. It is clear that both in adolescents and in pre-adolescents, migraine is frequent. Diagnostic criteria for migraine and chronic migraine are certainly over-restrictive for young children. Migraine often lasts less than 1 hour in young children. A vulnerable population at risk of migraine progression also exists, likely reflecting increased biological predisposition, but also early life exposures. Indeed, it seems that even prenatal exposures of certain substances may increase the risk of migraine progression. Of relevance is the frequency of headaches within a family. Finally, migraine seems to be associated with behavioral hyperactivity, but is not comorbid with attention-deficit disorder and hyperactivity. PMID- 20572879 TI - The role of computed tomography in the diagnostic work-up of headache patients in Nigeria. AB - OBJECTIVE: To determine the yield of computed tomography (CT) scan of the brain in the evaluation of patients presenting with headache at the University of Port Harcourt Teaching Hospital (UPTH). BACKGROUND: Headache is a pain in the head or upper neck. It is one of the most common locations of pain in the body that leads patients to see a physician. CT scan is invaluable as an imaging tool in assessment of intracranial lesions that may present with headache. METHODS: The records of all the patients referred from a variety of inpatient and outpatient settings to the radiology department of UPTH with the main complaint of headache for brain (CT) scan were identified. Data extracted include referral source, indication for CT, age, sex, presenting complaint, duration of headache, and CT findings. The data were analyzed using SPSS 14.0 statistical package. RESULTS: A total of 80 patients with chronic or recurrent headache met the selection criteria. The age range was 16 to 85 years with a mean of 39.8 +/- 14.62 years. There were 36 males and 44 females with male to female ratio of 1 :1.2. About half of the patients were <= 45 years. Of the total number, 72 (90%) patients had normal CT findings, 2 (2.5%) had cerebral atrophy, 2 (2.5%) had cerebral edema, 2 (2.5%) had intracerebral hematoma while 1 (1.25%) patient each had cerebral infarction and subdural hematoma, respectively. There was no case of brain tumor. CONCLUSIONS: The yield of correctable abnormalities from routine CT scan of the brain in headache patients with normal neurologic findings is low and does not justify its use in a resource poor country. (Headache 2010;50:1346-1352). PMID- 20572880 TI - Increased prevalence of sleep disorders in chronic headache: a case-control study. AB - OBJECTIVES: The aim of our study was to investigate the prevalence of sleep disorders in chronic headache patients and to evaluate the role of psychiatric comorbidity in the association between chronic headache and sleep complaints. BACKGROUND: The prevalence of sleep disorders in chronic headache has been seldom investigated, although from the earliest description chronic headache has been associated with sleep disturbances. On the contrary, mood disorders are commonly associated with both sleep disturbances and chronic headache--each of which are, in turn, core features of mood disorders. Therefore, it may be important to discriminate between sleep problems that can be attributed to a comorbid psychiatric disorder, and those specifically associated with headache. Only a few studies investigating the association of chronic headache with sleep difficulties have also taken into account to consider the possible role of anxiety and depression. PATIENTS AND METHODS: A total of 105 consecutive patients with daily or nearly daily headache and 102 patients with episodic headache, matched by age, sex, and type of headache at onset, underwent a structured direct interview about their sleep habits and psychiatric diseases. RESULTS: In total, 80 out of 105 patients with chronic headache received a diagnosis of medication overuse headache, 21 patients were classified as chronic migraine and 4 as chronic tension-type headache without drug overuse. PATIENTS: Patients with chronic headache showed a high prevalence of insomnia, daytime sleepiness, and snoring with respect to controls (67.7% vs 39.2%, 36.2% vs 23.5%, and 48.6% vs 37.2%, respectively). Forty-five patients with chronic headache (42.9%) had psychiatric comorbidity (anxiety and/or depressive disorders), vs 27 episodic headache patients (26.5%). Multivariate analysis disclosed that low educational level, lower mean age at headache onset, and insomnia are independently associated with chronic headache. CONCLUSIONS: Patients with chronic headache had a high prevalence of sleep complaints. Insomnia may thus represent an independent risk factor for headache chronification. Recognition of sleep disorders, alone or in association with depression or anxiety, may be useful in episodic headache patients to prevent chronification. PMID- 20572881 TI - Cytoplasmic beta-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas. AB - AIMS: beta-Catenin is an important molecule in cancer biology. Membranous beta catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. METHODS AND RESULTS: Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess beta catenin expression. Increasing beta-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of beta-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. CONCLUSIONS: This is one of the largest prognostic studies of beta-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic beta-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic beta-catenin could be used as a prognostic marker for less aggressive disease. PMID- 20572882 TI - Stratum corneum free amino acids following barrier perturbation and repair. AB - Modulation of the skin environment after stratum corneum (SC) perturbation has profound effects on the rate and effectiveness of barrier repair. Intermediate water exposure, e.g. moderate relative humidity, may provide the optimum water gradient for SC repair. More rapid recovery with semipermeable (SP) films in vivo was associated with increased hydration measured as moisture accumulation rate. We hypothesized that (i) damaged SC recovering under the high water exposure of full occlusion (FO) would have lower free amino acids (FAA) than sites with low hydration (no occlusion, NO) and semi-occlusion (SP, semipermeable film, intermediate hydration) and (ii) SC under semi-occlusion would have higher FAA than with low hydration. Volar forearm sites in 15 healthy adults were perturbed via cellophane tape stripping and treated with SP, FO and NO for five days. Barrier recovery rate, hydration, dryness and erythema were determined. Serial SC samples (n=15) were collected on day 5 and FAA quantified using reverse-phase HPLC and fluorescence detection. The cumulative protein removed was higher for SP than the control, NO and FO. FAA as total, individual amino acids and citrulline were consistently higher in the control than the three damaged sites. Generally, FAA was higher in NO than FO. Citrulline was higher for NO than SP and FO over the sampled SC. Levels were higher for SP than FO in certain, but not all of the FAAs. FAA was inversely correlated to barrier integrity. Skin hydration was relatively constant at the external microenvironment of the SP site, whereas the NO and FO had a reduction, i.e. a gradient, over the time. Overall, barrier recovery under conditions of a decreasing hydration gradient produced SC with higher levels of FAA than did conditions of full occlusion. PMID- 20572883 TI - Assessment of the variation of skin barrier function with anatomic site, age, gender and ethnicity. AB - The skin is the largest organ of the human body and its functions include protection, thermoregulation sensation and secretion. Significant advances in our understanding of how the morphology and physiology of the skin contribute to the skin's barrier role have been achieved in recent years. The aim of this review is to summarize the principal approaches which have been used to assess variation in skin barrier function with anatomic site, age, gender, and ethnicity. The methods discussed include trans-epidermal water loss (TEWL) measurement, assessment of corneocyte size, response to vasoactive compounds and attenuated total reflectance Fourier transform infrared (ATR-FTIR) interrogation of skin. The utility of the various methods is considered and the most important findings in the literature to date are highlighted. PMID- 20572884 TI - Temperature as a moisture cue in haptics on hair. AB - A mechanism for giving a moisturized or dried-out feeling to hair was investigated. A two-step approach was conducted in order to elucidate the issue. First, we have reviewed previous studies that are related to the sensory perception of materials not only in cosmetic industry but also in other fields, such as textile and architecture industries, and established a hypothesis. Second, we have verified the hypothesis derived from the first step and identified the mechanism for the moisturized or dried-out feeling that people feel by measuring the heat transfer characteristic, q(max) . The results revealed that the moisturized or dried-out feeling that people feel at the moment of contact with hair was highly related to the temperature drop at the skin surface. The results also revealed that the moisturized or dried-out feeling strongly depends on the hair shape (meandering and diameter), surface damage and the water content of hair fibres which constitute the hair swatch. The moisturized feeling, however, was not related to the water content of hair fibres at a constant relative humidity (RH), as the differences in the water content of the hair fibres at a constant RH were too small for the recognition of the difference in the moisturized feeling. PMID- 20572885 TI - Oral malodour and active ingredients for treatment. AB - Oral care preparations are widely used for the treatment of oral malodour as over the-counter products. Bad breath is highly distressing to an individual's confidence during social interaction, which is a large concern nowadays as the consumption of these products is increasing worldwide. However, oral deodorant ingredients are rarely studied compared with other cosmetic ingredients, and the only preparations which are well known are those contained in dentifrices and mouthrinses. This review briefly summarizes the compounds which cause oral malodour and the treatments available. The active ingredients in various preparations are emphasized and novel products are presented. PMID- 20572886 TI - Bioengineering and subjective approaches to the clinical evaluation of dry skin. AB - Dry skin (also known as xerosis) is a cutaneous reaction pattern indicative of abnormal desquamation, which has not only cosmetic considerations, but can also lead to the penetration of irritants and allergens through the stratum corneum (SC). Over the last few decades, our understanding of the structure, composition, formation and function of the SC has advanced tremendously; however, despite these advancements, the occurrence of dry skin remains prevalent in the adult population. The clinical evaluation of dry skin is therefore of significant importance to the cosmetic industry not only for understanding the condition but also for measuring the effects of treatment. Traditionally, dry skin has been evaluated by visual inspection, however, recently a variety of bioengineering techniques have emerged enabling the investigator to objectively assess the extent of xerotic conditions. The most frequently employed methods for the evaluation of dry skin are discussed in this review, including regression testing, squametry, measurement of transepidermal water loss, epidermal hydration, profilometry, confocal Raman spectroscopy, optical coherence tomography, in vivo confocal microscopy and magnetic resonance imaging. PMID- 20572887 TI - Lavender, tea tree and lemon oils as antimicrobials in washing liquids and soft body balms. AB - The aim of this study was to evaluate the antimicrobial activity of commercial essential oils: lavender, tea tree and lemon, antimicrobials in washing liquid and O/W soft body balm. The inhibition efficacy of essential oils in washing liquid (1% alone or in mixtures), in soft body balm (0.5% alone), as well as combined with the synthetic preservative DMDM hydantoin and 3-iodo-2-propynyl butyl carbamate mixture (0.1 and 0.3%), was tested against S. aureus ATCC 6538, P. aeruginosa ATCC 9027, Candida sp. LOCK 0008 and A. niger ATCC 16404 in compliance with the European Pharmacopoeia standards. The components of the system preserving soft body balm were supplemented with a solubilizer. Washing liquids containing only essential oils met Criterion A E.P. only for S. aureus, Candida sp. and A. niger. In soft body balm formulations, oils at a concentration of 0.5% did not reveal any preserving activity. The introduction of a solubilizer to a system containing 0.5% tea tree oil led to a substantial increase in the bacteriostatic activity of the formulation, but did not significantly affect its fungistatic properties. A combination of 0.5% tea tree oil, 5% solubilizer and 0.3% synthetic preservative ensured the microbiological stability of soft body balm in accordance with Criterion A E.P. PMID- 20572888 TI - Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin. AB - The aim of this study was to evaluate different urea-containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short-term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2-10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro-Creme), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin's natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea-containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea-containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care. PMID- 20572889 TI - Maintenance of the ubiquitin-proteasome system activity correlates with visible skin benefits. AB - Researches on longevity and anti-ageing molecules have clearly evidenced the potential to increase lifespan of the cells. These recent scientific data raise interests and questions on the capacity of the cells to live longer and maintain their fundamental mechanisms of protection, reparation or degradation of abnormal proteins to maintain their capital of healthy and functional cellular activity. In this concern, this study was focused on the ubiquitin-proteasome system as an essential cellular tool to maintain the pool of functionally active proteins allowing renewal of proteins and degradation of damaged proteins. As the proteasome keeps the 'cells health capital', it should be particularly interesting to associate the maintenance of the proteasome activity with increasing longevity. Indeed, although oxidative stress damage increases with ageing leading to collagen and cellular membrane alterations, it also leads to a reduction in the proteasome activity which is critical for the cells. The aim of this study was to better understand the cellular role of the proteasome and to provide new data showing the skin beneficial effects in activating the overall system of ubiquitination and proteasomal degradation. For this purpose, in vitro, ex vivo and in vivo experiments were performed to evaluate the effects of maintaining the ubiquitin-proteasome activity in basal and stress conditions on young versus aged cells. Experiments have included evaluation of a newly developed dimerized tripeptide targeting specifically the ubiquitin-proteasome pathway. Our results have demonstrated that maintenance of this essential mechanism that participates in abnormal protein elimination and protein renewal allows maintaining cellular integrity that correlates with visible skin benefits. PMID- 20572890 TI - A new wrinkle on old skin: the role of elastic fibres in skin ageing. AB - Cutaneous ageing is the result of two distinct, biological processes which may occur concurrently: (i) the passage of time, termed intrinsic ageing and (ii) environmental influences, termed extrinsic ageing. Intrinsic ageing of the skin is a slow process which causes changes in tissue structure and impairs function in the absence of additional biological, chemical and physical factors. The clinical features of intrinsically aged skin are not usually evident until old age when, although smooth and unblemished, the skin surface appears pale and is characterized by fine wrinkles with occasional exaggerated expression lines. Functionally, intrinsically aged skin is dry and less elastic than more youthful skin. In contrast, extrinsically aged skin is exemplified by deep, coarse wrinkles, mottled hyperpigmentation and a marked loss of elasticity and recoil. The two major environmental influences which induce extrinsic ageing are: (i) chronic exposure to solar ultraviolet (UV) irradiation (termed photoageing) and (ii) smoking. This review discusses the changes associated with the ageing process in the skin, with particular emphasis on the role played by the elastic fibre network in maintaining dermal function. The review concludes with a discussion of a short-term assay for independent assessment of the efficacy of anti-ageing cosmetic products using the elastic fibre component fibrillin-1 as a biomarker of extracellular matrix repair. PMID- 20572891 TI - Epidermal and dermal changes in response to various skin rejuvenation methods. AB - During the last years, a number of new devices have been developed to improve the dermal and epidermal signs of photo- and chronological skin ageing. There are well-established ablative and non-ablative skin resurfacing options using different lasers and light sources, but side effects have been observed frequently. A recently developed photorejuvenation method using non-thermal stimulation of skin cells with low energy and narrow band light has been termed photomodulation. Light emitting diodes are the ideal source of this kind of light that stimulate mitochondrial cell organelles leading to up-regulation of cytochrome electron transport pathway leading to mitochondrial DNA gene modulation. This paper reviews the most current knowledge of intrinsic and extrinsic changes of ageing and summarizes different systems for skin rejuvenation with focus on non-thermal non-ablative skin rejuvenation modalities. PMID- 20572892 TI - Distribution of HLA-B27 in Romanian spondyloarthritides patients. AB - The analysis of 310 Romanian spondyloarthritides patients confirmed the association of the HLA-B27 marker with the susceptibility to different diseases of this group. For ankylosing spondylitis, the HLA-B27 frequency in Romanian patients (72.1%) was similar to that found in several regions in the Mediterranean area. PMID- 20572893 TI - HLA alleles and fissured tongue. AB - The aim of this study was to investigate the linkage between HLA and fissured tongue. Sixty- nine individuals with fissured tongue and 125 healthy volunteers were typed for HLA-DRB1*. The results showed increased frequency of HLA-DRB1*08 (P < 0.001), HLA-DRB1*14 (P < 0.01), HLA-DRB1*11 (P < 0.05) and HLA-DRB1*16 (P < 0.05), while HLA-DRB1*03 and HLA-DRB1*07 frequency was decreased (P < 0.05). PMID- 20572898 TI - Finite element analysis of performance in the skulls of marmosets and tamarins. AB - Reliance on plant exudates is a relatively rare dietary specialization among mammals. One well-studied example of closely related exudate feeders is the New World marmosets and tamarins. Whereas marmosets actively gouge tree bark with their incisors to stimulate the flow of sap, tamarins are opportunistic exudate feeders that do not gouge bark. Several studies of the dentaries and jaw adductors indicate that marmosets exhibit specializations for increased gape at the expense of bite force. Few studies, however, have looked to the cranium of marmosets for evidence of functional specializations. Using 3D finite element models of the marmoset Callithrix jacchus and the tamarin Saguinus fuscicollis, we investigated the performance of the cranium under loading regimes that mimicked unilateral molar biting and bark-gouging. We investigated three measures of performance: the efficiency with which muscle force is transferred to bite force, the extent to which the models are stressed (a predictor of failure), and the work expended by muscles as they deform the skull (total strain energy). We found that during molar biting the two models exhibited similar levels of performance, though the Saguinus model had slightly higher mechanical efficiency, a slightly lower state of stress, and expended more energy on deformation. In contrast, under the bark-gouging load, Callithrix exhibited much higher mechanical efficiency than Saguinas, but did so at the expense of more work and higher levels of von Mises stress. This analysis illustrates that differences in the shapes of the skulls of Callithrix and Saguinus confer differences in performance. Whether these aspects of performance are targets of selection awaits broader comparative analyses. PMID- 20572899 TI - Distribution of glial cell line-derived neurotrophic factor receptor alpha-1 in the brain of adult zebrafish. AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent trophic factor for several types of neurons in the central and peripheral nervous systems. The biological activity of GDNF is mediated by a multicomponent receptor complex that includes a common transmembrane signaling component (the rearranged during transfection (RET) proto-oncogene product, a tyrosine kinase receptor) as well as a GDNF family receptor alpha (GFRalpha) subunit, a high-affinity glycosyl phosphatidylinositol (GPI)-linked binding element. Among the four known GFRalpha subunits, GFRalpha1 preferentially binds to GDNF. In zebrafish (Danio rerio) embryos, the expression of the GFRalpha1a and GFRalpha1b genes has been shown in primary motor neurons, the kidney, and the enteric nervous system. To examine the activity of GFRalpha in the adult brain of a lower vertebrate, we have investigated the localization of GFRalpha1a and GFRalpha1b mRNA and the GFRalpha1 protein in zebrafish. GFRalpha1a and GFRalpha1b transcripts were observed in brain extracts by reverse transcription-polymerase chain reaction. Whole-mount in situ hybridization experiments revealed a wide distribution of GFRalpha1a and GFRalpha1b mRNAs in various regions of the adult zebrafish brain. These included the olfactory bulbs, dorsal and ventral telencephalic area (telencephalon), preoptic area, dorsal and ventral thalamus, posterior tuberculum and hypothalamus (diencephalon), optic tectum (mesencephalon), cerebellum, and medulla oblongata (rhombencephalon). Finally, expression patterns of the GFRalpha1 protein, detected immunohistochemically, correlated well with the mRNA expression and provided further insights into translational activity at the neuroanatomical level. In conclusion, the current study demonstrated that the presence of GFRalpha1 persists beyond the embryonic development of the zebrafish brain and, together with the GDNF ligand, is probably implicated in the brain physiology of an adult teleost fish. PMID- 20572901 TI - Intimal thickening of coronary arteries in the rabbitfish, Chimaera monstrosa L. (Chondrichthyes: Holocephali). AB - This study is the first to report the occurrence of intimal thickening of coronary arteries in a holocephalan, namely the rabbitfish, Chimaera monstrosa. The sample studied consisted of five hearts from rabbitfish with body weights ranging between 12 g and 1116 g. The specimens were fixed in formalin, in methanol:acetone:water (MAW), or in paraformaldehyde and were examined by brightfield and polarization light microscopy. Coronary arteries from three larger animals displayed focal intimal thickenings, which were located in the left main coronary artery trunk, at the level of the cono-ventricular junction, and in several intramyocardial ventricular arteries. The vascular changes were characterized by myointimal proliferation, breakage or absence of the inner elastic lamina, and, in one case, by increased collagen within the myointimal proliferation. Taking into account the severity of the coronary arterial changes, their location, and the body weight of the affected animals, we conclude that (1) these changes are age-related in the rabbitfish and (2) local intense mechanical tension seems to be an important factor in their formation in this species. PMID- 20572900 TI - New insights into the relationship between suture closure and craniofacial dysmorphology in sagittal nonsyndromic craniosynostosis. AB - Premature closure of the sagittal suture occurs as an isolated (nonsyndromic) birth defect or as a syndromic anomaly in combination with other congenital dysmorphologies. The genetic causes of sagittal nonsyndromic craniosynostosis (NSC) remain unknown. Although variation of the dysmorphic (scaphocephaly) skull shape of sagittal NSC cases has been acknowledged, this variation has not been quantitatively studied three-dimensionally (3D). We have analyzed the computed tomography skull images of 43 infants (aged 0.9-9 months) with sagittal NSC using anatomical landmarks and semilandmarks to quantify and characterize the within sample phenotypic variation. Suture closure patterns were defined by dividing the sagittal suture into three sections (anterior, central, posterior) and coding each section as 'closed' or 'fused'. Principal components analysis of the Procrustes shape coordinates representing the skull shape of 43 cases of NSC did not separate individuals by sex, chronological age, or dental stages of the deciduous maxillary first molar. However, analysis of suture closure pattern allowed separation of these data. The central section of the sagittal suture appears to be the first to fuse. Then, at least two different developmental paths towards complete fusion of the sagittal suture exist; either the anterior section or the posterior section is the second to fuse. Results indicate that according to the sequence of sagittal suture closure patterns, different craniofacial complex shapes are observed. The relationship between craniofacial shape and suture closure indicates not only which suture fused prematurely (in our case the sagittal suture), but also the pattern of the suture closure. Whether these patterns indicate differences in etiology cannot be determined with our data and requires analysis of longitudinal data, most appropriately of animal models where prenatal conditions can be monitored. PMID- 20572902 TI - Experimental challenge studies in Vietnamese catfish, Pangasianodon hypophthalmus (Sauvage), exposed to Edwardsiella ictaluri and Aeromonas hydrophila. AB - The two main diseases in the pangasius catfish industry are bacillary necrosis of Pangasianodon (BNP) and motile aeromonas septicaemia (MAS), where the aetiological agents have been identified as Edwardsiella ictaluri and Aeromonas hydrophila, respectively. In this study, apparently healthy Pangasianodon hypophthalmus were exposed to E. ictaluri, A. hydrophila or both bacterial species by intraperitoneal injection or immersion. There were 20 fish per treatment group, and the bacterial isolates used for the study were recovered from natural infections of BNP or MAS in farmed Vietnamese P. hypophthalmus. The results of the experimental infections mimicked the natural disease outbreaks reported from these pathogens in P. hypophthalmus. Furthermore, it was clearly demonstrated that E. ictaluri was only recovered from the fish exposed to the bacterium and not recovered from the animals receiving A. hydrophila. PMID- 20572903 TI - Association between periodontal condition and use of tongue piercing: a case control study. AB - OBJECTIVE: This cross-sectional study aimed to evaluate the periodontal status and risk factors for gingival recession in individuals with tongue piercings. METHODS: Sixty cases (individuals with tongue piercings) and 120 controls (non users) in Brazil, between 13 and 28 years of age, from both genders and a mix of races were selected. The clinical evaluation of patient oral health records included periodontal parameters and the presence of tooth fracture. Cases and controls were compared with demographic, behavioural and clinical variables of interest. Risk variables for the occurrence of gingival recession were identified in multivariate regression models, with linear and logistic regressions. RESULTS: The case group presented a higher prevalence and severity of gingival recession when compared with the control group. Individuals with tongue piercings presented an 11 times greater chance for the occurrence of gingival recession in the anterior lingual mandibular region as compared with controls (OR=11.0, 95% CI 5.02-24.09). The presence of gingival recession in the anterior lingual mandibular region was associated with the use of piercings, age, male gender and bleeding on probing. CONCLUSIONS: The use of tongue piercings was strongly associated with the occurrence of gingival recession in the anterior lingual mandibular region. PMID- 20572904 TI - Arterial reocclusion and persistent distal occlusion after thrombus aspiration. AB - BACKGROUND AND PURPOSE: Early reocclusion of intracranial arteries can lead to poor clinical outcome. We report reocclusion detection after endovascular clot aspiration, followed by administration of GPIIb-IIIa antagonist under continuous ultrasound monitoring. CASE DESCRIPTION: A 73-year-old man developed the right middle cerebral artery (MCA) occlusion with NIHSS 17 points, 6 days after aortic valve replacement. Recanalization was achieved with PenumbraTM system and reocclusion was detected with transcranial Doppler (TCD) 30 minutes postcompletion of intra-arterial procedure. Proximal recanalization was achieved with the second thrombus aspiration while M2 MCA occlusion persisted beyond the reach of the device. Intravenous abciximab was administered under continuous TCD monitoring. Recanalization with Thrombolysis in Brain Ischemia (TIBI) flow grade 4 was observed at 60 minutes postintervention accompanied with clinical recovery to NIHSS 3 points. Abciximab was given for 12 hours with no hemorrhagic transformation on repeat CT scan. Patient was discharged home with mild left pronator drift and facial droop, and his modified ranking score was 1 at 6-week follow-up visit. CONCLUSIONS: Early arterial reocclusion can occur after successful thrombus aspiration while GPIIb-IIIa antagonist administration may lead to subsequent recanalization of persisting distal occlusions not amenable to mechanical removal. PMID- 20572905 TI - Gray matter alterations in first-admission adolescents with schizophrenia. AB - BACKGROUND AND PURPOSE: Imaging studies of patients with schizophrenia have described a variety of cerebral alterations. However, long-term medication and the chronicity of the disorder may have contributed substantially to these alterations. Studies examining patients in the early stages of the disorder reduce the possibility of such confounding factors but are rare. In light of this, the aim of the present study was to examine adolescents in the early stages of the disorder to observe primary structural brain abnormalities. METHODS: Gray and white matter were measured in 13 adolescents with schizophrenia and 13 healthy controls matched for age, gender, handedness, and school type using voxel based morphometry. RESULTS: Subjects with schizophrenia displayed decreased gray matter in the cerebellar vermis, and alterations in the left putamen and in several parts of the visual system. CONCLUSIONS: These findings support cerebellar involvement in the pathogenesis of schizophrenia, and the alterations observed in several parts of the visual system may provide insights into the nature of hallucinations and delusional interpretations. PMID- 20572906 TI - Infarction limited to both middle cerebellar peduncles. AB - BACKGROUND: The middle cerebellar peduncle (MCP) is supplied mainly by the anterior inferior cerebellar artery and partly by the superior cerebellar artery. The bilateral MCP infarctions in previous patients were attributed to alternations of two vessels, such as the unilateral vertebral artery and basilar artery or both vertebral arteries. METHODS: We describe a case of bilateral acute infarction of the MCP and the stroke was apparently caused by occlusion of only one vertebral artery. RESULTS: A 63-year-old man presented with vertigo and auditory distortion, accompanied by difficulty in speaking and walking. Neurological examinations revealed bilateral horizontal nystagmus, scanning speech, and ataxia of the trunk and all four limbs. Brain MRI showed high signal intensity in the both MCPs on diffusion-weighted and T2-weighted images. Enhanced computed tomographic angiography showed fusiform dilatation at the V4 level of the right vertebral artery; a false lumen was evident in the dilatation. Right vertebral angiography showed occlusion from the C1 level to the foramen magnum. Left vertebral angiography revealed a hypoplastic vertebral artery with a maximum diameter of 2.5 mm. CONCLUSIONS: Alternations of the vertebral artery should be considered as a possible cause of MCP infarction, particularly when such anomalies are suggested. PMID- 20572907 TI - Characteristic neuroimaging in patients with tumefactive demyelinating lesions exceeding 30 mm. AB - BACKGROUND AND PURPOSE: Features of tumefactive demyelinating lesion (TDL) on magnetic resonance imaging (MRI) can facilitate the differential diagnosis of TDL and neoplastic lesions, but vary considerably among patients. The larger TDL grows, the more difficult it becomes to differentiate TDL from neoplastic lesions. The purpose of this study was to elucidate typical MRI features in 12 patients with large TDL (>30 mm in diameter). METHODS: We identified 12 patients with large TDL (six men, six women; age range 17-64 years, median age 27 years) and studied the clinical histories and the results of laboratory and various radiological studies in these patients. All cases of clinically definite multiple sclerosis were diagnosed in accordance with McDonald's revised criteria. RESULTS: Common MRI features of large TDLs included variable degrees of mass effect (71%) and edema (100%), a T2 hypointense rim (79%), venular enhancement (57%), and peripheral restriction on diffusion-weighted images (50%). Ring enhancement (38%), open-ring enhancement (31%), or decreased N-acetylaspartate ratios on magnetic resonance spectroscopy (22%) were less frequently observed. Brain angiography demonstrated venous dilatations on and around the TDL. CONCLUSIONS: The diagnosis of large TDL is challenging. Our findings suggest that multiple venous dilatations on and around TDLs on angiography can facilitate diagnosis. PMID- 20572908 TI - Multimodality MRI and MRA for decision making in minor stroke: a case with internal carotid and distal middle cerebral artery occlusion. AB - We report the case of a 65-year-old man who presented with mild, rapidly improving stroke symptoms. Acute magnetic resonance imaging disclosed no diffusion abnormalities but a tandem internal carotid artery/distal middle cerebral artery occlusion associated with a large corresponding deficit on perfusion imaging. In addition, there was a cross-flow to the middle cerebral artery via the anterior communicating artery. Therefore, intravenous thrombolysis was initiated that led to rapid reopening of the middle cerebral artery and left the patient free of symptoms. Our observation highlights the possible benefit of systemic thrombolytic treatment even in the setting of an internal carotid artery occlusion and the substantial contribution of multimodal magnetic resonance imaging for a risk-benefit estimate. PMID- 20572909 TI - Imaging of intracranial plaques with black-blood double inversion recovery MR imaging and CT. AB - BACKGROUND: We evaluated the feasibility of black-blood double inversion recovery magnetic resonance imaging (BBDIR) and CT imaging (CTI) for depiction of IAPs. METHODS: We performed BBDIR on 20 control subjects and 13 patients with acute ischemic stroke. We measured the thickness of the normal vessel wall in control subjects and the maximal and minimal thickness of IAPs in patients on BBDIR. We evaluated signal intensity (SI) and the eccentricity of the IAP on BBDIR, and abnormal wall thickening and CT attenuation of IAPs on CTI. We correlated imaging features of BBDIR and CTI in the patients. RESULTS: The difference of wall thickness between control and patient group was statistically significant (control subjects; basilar artery 0.6 mm, MCA 0.51 mm, and patients; maximal 2.34 mm, minimal 1.3 mm, P value<=.001). The IAP showed eccentric remodeling and heterogeneous SI with the regions of high SI on BBDIR. CTI could not reveal abnormality in 10 patients. Suspicious intraplaque hemorrhage and calcification was demonstrated in 3 patients by CTI. CONCLUSIONS: BBDIR could reveal normal and abnormal wall of large intracranial arteries. CTI had limited role for detection of IAP, however, correlation of BBDIR and CTI could provide further characterization of the IAP's in terms of intraplaque calcification and hemorrhage. PMID- 20572910 TI - Idiopathic hypoglossal nerve laceration detected by high-resolution three dimensional constructive interference in steady state magnetic resonance imaging. AB - A 55-year-old man presented with acute onset dysarthria caused by left hypoglossal palsy. He had neither surgery nor injury prior to the onset of his symptoms. We detected no abnormalities with conventional magnetic resonance imaging (MRI) except for a slight gadolinium enhancement of the left hypoglossal nerve. Three-dimensional constructive interference in steady state MRI (CISS MRI) showed curling and thickening of the left hypoglossal nerve and fluid accumulation in the hypoglossal nerve canal. A systemic survey found no malignancies. After 8 months, sustained left hypoglossal palsy and no change in the MRI led to the diagnosis of idiopathic hypoglossal nerve laceration with evulsion. In such patients, the cause of the defect is not always apparent and 3 dimensional CISS MRI may resolve this issue. PMID- 20572911 TI - The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: a retrospective series of 24 patients. AB - BACKGROUND AND PURPOSE: Some patients with posterior reversible encephalopathy syndrome (PRES) present with atypical clinical and neuroimaging findings. The purpose of this study is to review the clinical and neuroimaging findings in patients diagnosed with PRES. METHODS: We retrospectively included all patients diagnosed with PRES between January 2005 and March 2009. We reviewed demographic, clinical and laboratory data, neuroimaging findings, and prognosis. RESULTS: Twenty-four patients were included with a median age of 19 years. The clinical presentations included seizures (91.7%), headache (83.3%), visual disturbance (62.5%), encephalophathy (29.2%), and paralysis (8.3%). Co-morbidities included systemic lupus erythematous (29.2%), kidney disease (20.8%), eclampsia (20.8%), renal artery stenosis (12.5%), Takayasu arteritis (4.2%), Sheehan's syndrome (4.2%), allergic purpura (4.2%), and acute intermittent porphyria (4.2%). Acute elevation of blood pressure was found in 22 patients (91.7%). Ten patients (41.7%) used steroids or immunosuppressants, three (12.5%) had acute renal failure before the symptoms. Atypical neuroimaging features included involvement of the frontal lobe (54.2%), basal ganglia (4.2%) or cortex (8.3%), and irreversible lesions (3/18, 16.7%). CONCLUSIONS: A large proportion of patients with PRES may present with atypical neuroimaging findings. Apart from the known risk factors, such as hypertension, immunosuppressants, and renal failure of various etiologies may be the precipitants of PRES. PMID- 20572912 TI - Assessment of collateral flow with multi-phasic CT: correlation with diffusion weighted MRI in MCA occlusion. AB - PURPOSE: To correlate collateral flow on multiphasic contrast enhancement computed tomography (CT) and graded ischemic changes on diffusion weighted MR in patients with acute middle cerebral artery (MCA) infarction. MATERIALS AND METHODS: A retrospective evaluation of diffusion weighted images (DWIs) and three phasic contrast enhanced CT (CECT) was performed on 11 patients with MCA occlusions. The area of ischemic change on DWIs was graded according to the Alberta Stroke Program Early CT Score (ASPECTS) criteria. To evaluate collateral flow on three phasic CECT, we counted the number of contrast enhancing MCA branches distal to the occlusion site at the sylvian fissure from predetermined axial images. The collateral ratios of counted numbers to those at the normal side were calculated at each phase (CR1, CR2, CR3). We then compared collateral ratios from the three phasic CECT with ASPECTS data from DWIs. RESULTS: Collateral ratios from the three phasic CECT were determined to be CR1 .48 +/- .27, CR2 .73 +/- .36 and CR3 .72 +/- .30. We discovered a correlation between both the CR2 and ASPECTS (r= .675, P= .023) and the CR3 and ASPECTS (r= .664, P= .026). CONCLUSION: The number of contrast enhancing branches distal to the MCA occlusion, as counted in the sylvian fissure on later phase images of multiphasic CECT, reflects the status of collateral flow, and correlates with ASPECTS on DWIs. PMID- 20572913 TI - Restricted diffusion in a thrombosed anterior cerebral artery aneurysm mimicking a dermoid cyst. AB - A neurologically intact 37-year-old woman presented with an acute severe frontal headache after a month of intermittent headaches. Multimodal radiological examination including computed tomography scan, magnetic resonance imaging, and conventional angiography demonstrated a 1 cm mass in the anterior interhemispheric region with heterogenous calcifications. Of note, MR revealed restricted diffusion within the mass. The presumptive diagnosis of dermoid tumor was made and the patient was scheduled for surgical resection. On operative exploration, a 1 cm thrombosed aneurysm was revealed. Thrombosed aneurysms must be considered in the differential diagnosis for midline cerebral masses with negative angiogram and restricted diffusion. This distinction has implications for the clinical management of the patient. PMID- 20572914 TI - Anti-phosphorylcholine-opsonized low-density lipoprotein promotes rapid production of proinflammatory cytokines by dendritic cells and natural killer cells. AB - BACKGROUND AND OBJECTIVE: Epidemiological and animal studies suggest that periodontal infections increase atherosclerosis risk. Periodontitis patients have elevated levels of anti-phosphorylcholine (anti-PC) reactive not only with numerous periodontal organisms but also with minimally modified low-density lipoprotein (mmLDL). Dendritic cells (DCs) reside in arterial walls and accumulate in atherosclerotic lesions. The ability of anti-PC to bind mmLDL prompted the hypothesis that opsonized mmLDL would stimulate DCs and enhance the production of proinflammatory cytokines that promote atherogenic plaque development. MATERIAL AND METHODS: Monocyte-derived DCs (mDCs) were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, then stimulated with mmLDL or with anti-PC-opsonized mmLDL. The anti-PC effect was determined using flow cytometry, cofocal microscopy and cytokine assays. The production of CD83, IL-12p35 mRNA, IL-12p40 mRNA, IL-12p70 and IL-10 by DCs was monitored. RESULTS: Dendritic cells stimulated with mmLDL expressed little CD83 and produced little IL-12p70. However, anti-PC-opsonized mmLDL enhanced DC maturation, as indicated by upregulated CD83 and rapid (<= 48 h) production of IL-12p70 if a source of interferon-gamma (IFN-gamma) was available. In leukocyte cultures, natural killer (NK) cells rapidly produced IFN-gamma (<= 48 h) when interacting with IL-12-producing DCs activated by anti-PC-opsonized mmLDL. Moreover, IFN-gamma promoted DC IL-12 responses that were further augmented when mmLDL was opsonized with anti-PC. CONCLUSION: Minimally modified LDL-stimulated DCs and NK cells were mutually stimulatory, with DC IL-12p70 needed by NK cells and with NK cell IFN-gamma needed by DCs. Moreover, production of these proinflammatory cytokines was markedly enhanced when LDL was opsonized by anti-PC. In short, the data suggest that the elevated anti-PC levels in periodontitis patients could promote a mechanism that facilitates atherosclerosis. PMID- 20572915 TI - Human cementoblasts express enamel-associated molecules in vitro and in vivo. AB - BACKGROUND AND OBJECTIVE: Cementum is a mineralized tissue that facilitates the attachment of periodontal ligament to the root and surrounding alveolar bone and plays a key role in the regeneration of periodontal tissues. The molecular mechanisms that regulate the proliferation and differentiation of cementoblasts, however, have not been elucidated to date. Enamel molecules are believed to regulate cementoblast differentiation and to initiate the formation of acellular extrinsic fiber cementum. The purpose of this study was therefore to isolate and culture human root-derived cells (HRDC) in order to determine whether they are able to express both cementum and specific enamel proteins and subsequently to confirm these findings in vivo. MATERIAL AND METHODS: Human root-derived cells were isolated and expanded in vitro. Cells were characterized using RT-PCR, immunostaining, western blotting and by examination of total mRNA to determine the expression of cementum and enamel markers. Human periodontal tissues were also examined for the expression of enamel-related proteins by immunostaining. RESULTS: We showed that HRDC express mRNA corresponding to ameloblastin (AMBN), amelogenin (AMEL), enamelin (ENAM), tuftelin (TUFT) and cementum-associated molecules such as cementum protein 1 (CEMP1) and cementum attachment protein (CAP). Western blotting revealed that HRDC express both AMEL and AMBN gene products, as well as the cementum markers CEMP1 and CAP. In vivo, we have showed that AMBN and AMEL are expressed by cementoblasts lining cementum, paravascular cells and periodontal ligament cells. CONCLUSION: These results suggest that enamel-associated and cementum-associated proteins could act synergistically in regulating cementoblast differentiation and cementum deposition and offer new approaches on how the cementogenesis process is regulated. PMID- 20572916 TI - Micro-computerized tomography analysis of alveolar bone loss in ligature- and nicotine-induced experimental periodontitis in rats. AB - BACKGROUND AND OBJECTIVE: Nicotine reportedly is a risk factor for periodontitis, but accurate data regarding nicotine-induced alveolar bone loss is lacking. The aim of this study was to quantitatively assess alveolar bone loss in ligature- and nicotine-induced periodontitis in rats using micro-computerized tomography (micro-CT). MATERIAL AND METHODS: Thirty-six adult male rats were treated by placing silk ligatures around the cervixes of the right second maxillary molar; the contralateral tooth was untreated. After ligation, the animals were randomly divided into three groups: group A received intraperitoneal injections of saline solution, group B received 0.83 mg of nicotine/kg/d, and group C received 1.67 mg of nicotine/kg/d. Six animals in each group were killed on days 14 and 28 after ligature placement, and then micro-CT examinations were conducted. RESULTS: In all groups, bone mineral density (BMD), bone volume fraction (BVF), trabecular number (Tb.N) and trabecular thickness (Tb.Th) values of the ligated sides were significantly lower than those of the unligated sides (p < 0.001), whereas alveolar bone height loss (ABHL) and trabecular separation (Tb.Sp) of the ligated sides were significantly higher than those of the unligated sides (p < 0.001). Compared with the control group, nicotine administration increased the ABHL value and decreased the BMD, BVF and Tb.Th values of both sides in a dose-dependent manner (p < 0.05). CONCLUSION: Our results confirmed that ligature could cause significant loss in the trabecula of alveolar bone, and daily administration of nicotine resulted in further bone loss and microstructure deterioration. PMID- 20572917 TI - Disruption of periodontal integrity induces expression of apin by epithelial cell rests of Malassez. AB - BACKGROUND AND OBJECTIVE: It has been suggested that epithelial cell rests of Malassez (ERM) may express enamel matrix proteins and play an important role in periodontal regeneration. Two novel proteins, apin (APIN) and amelotin (AMTN), produced by maturation-stage ameloblasts and junctional epithelium, have recently been identified. The objective of this study was to evaluate whether the ERM express APIN and AMTN under normal conditions and after periodontal challenge. MATERIAL AND METHODS: Gingivectomy and orthodontic tooth movement were carried out on the left side of the maxillae of rats. The control group included the untreated contralateral side of these animals and the maxillae of normal, untreated rats. Animals were sacrificed by intracardiac perfusion on days 3 and 5 after the experimental procedures and maxillary molars were decalcified and processed for paraffin embedding. Immunohistochemistry was used to evaluate the expression of various ameloblast products, including APIN, AMTN, ameloblastin (AMBN) and amelogenin (AMEL). RESULTS: At 3 and 5 days after periodontal challenge, ERM were more evident in the periodontal ligament along the root surface and in the root furcations. Immunodetection of APIN, but not of the other three proteins, was observed in the ERM following the disruption of periodontal integrity. No immunolabeling for APIN, AMTN, AMBN and AMEL was detected in the ERM under normal conditions. CONCLUSION: The expression of APIN at an early time point following disruption of periodontal integrity suggests that this protein may be part of the cascade of events leading to the activation of ERM during periodontal healing and regeneration. PMID- 20572918 TI - Investigation of interleukin-13 gene polymorphisms in individuals with chronic and generalized aggressive periodontitis in a Taiwanese (Chinese) population. AB - BACKGROUND AND OBJECTIVE: The interleukin-13 (IL-13) -1112 C/T polymorphisms have been analyzed previously in a North European population of patients with aggressive periodontitis. The present study was carried out to investigate the association of polymorphisms in the IL-13 gene with susceptibility to periodontitis in a Taiwanese population. MATERIAL AND METHODS: The genotyping of IL-13 -1112 C/T polymorphisms in 60 patients with aggressive periodontitis, 204 patients with chronic periodontitis and 95 healthy controls was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Genotypes and allele frequencies among study groups were compared using Fisher's exact test (p < 0.05). Pearson's chi-square test was used for analysis of the Hardy-Weinberg equilibrium. RESULTS: The distributions of CC genotypes and C alleles between patients with aggressive periodontitis and healthy controls were significantly different (p = 0.034 and 0.046). After adjustment for age, gender, betel nut chewing and smoking status using logistic regression analysis, the odds ratio (OR) was 6.45 [95% confidence interval (CI) = 1.99-23.72, p = 0.003] for aggressive periodontitis. However, the CC genotype was only significantly associated with the risk of aggressive periodontitis in the nonsmoking group (OR = 4.48, 95% CI = 1.31-16.93, p = 0.020). CONCLUSION: The CC genotype or C allele appears to increase the risk of developing aggressive periodontitis in Taiwanese subjects. PMID- 20572919 TI - Relationship between oral malodor and the menstrual cycle. AB - BACKGROUND AND OBJECTIVE: Sex hormones have been suggested to be important modifying factors that may influence the pathogenesis of periodontal disease. This study examined changes in volatile sulfur compounds (VSC) levels, clinical parameters and bacterial levels during the menstrual cycle. MATERIAL AND METHODS: The study group consisted of 10 female subjects with periodontitis and 12 periodontally healthy female subjects. Clinical and bacterial measurements were performed for all subjects during the ovulation and follicular phases of the menstrual cycle. RESULTS: Bleeding on probing (BOP) was significantly increased in the ovulation phase in periodontitis subjects but not in healthy subjects. The VSC levels in subjects with periodontitis increased 2.2-fold in the ovulation phase compared with the follicular phase. In the ovulation phase, VSC levels and BOP were significantly higher in subjects with periodontitis than in healthy subjects. The number, and salivary levels, of Prevotella intermedia in subjects with periodontitis were significantly higher in the ovulation phase than in the follicular phase. CONCLUSION: The present study indicated changes in VSC, BOP and P. intermedia during the menstrual cycles of women with periodontitis. PMID- 20572920 TI - Levels of specific immunoglobulin G to the forsythia detaching factor of Tannerella forsythia in gingival crevicular fluid are related to the periodontal status. AB - BACKGROUND AND OBJECTIVE: Forsythia detaching factor (FDF) is a putative virulence factor of Tannerella forsythia that induces detachment of adherent cells and interleukin-8 production in human fibroblasts. The objective of the present study was to clarify the relationship between anti-FDF IgG levels in gingival crevicular fluid and the clinical status in patients with periodontitis and in healthy subjects. MATERIAL AND METHODS: Gingival crevicular fluid and subgingival plaque samples were obtained from both the diseased and healthy sites of 37 patients with periodontitis and from 30 healthy subjects. Anti-FDF IgG levels were evaluated, and both the fdf gene and T. forsythia 16S ribosomal RNA (rRNA) were detected using the PCR. RESULTS: Anti-FDF IgG levels (of both diseased and healthy sites) of patients with periodontitis were significantly higher than those of healthy subjects. Among the patients with periodontitis, anti-FDF IgG levels of healthy sites were significantly higher than those of diseased sites and the levels showed negative correlations with probing pocket depth and clinical attachment level. Among the patients with periodontitis, T. forsythia 16S rRNA was detected in 18 of 37 diseased sites and in 5 of 29 healthy sites, and the fdf gene was detected in 19 of 37 diseased sites and in 7 of 29 healthy sites. By contrast, no healthy subjects were positive for T. forsythia 16S rRNA or the fdf gene. CONCLUSION: These data suggest that anti-FDF IgG levels in gingival crevicular fluid are related to the periodontal status. PMID- 20572921 TI - Purine nucleoside phosphorylase activity and expression are upregulated in sites affected by periodontal disease. AB - BACKGROUND AND OBJECTIVE: Purine nucleoside phosphorylase (PNP) is an enzyme that catalyzes the reversible phosphorolysis of purine nucleosides, playing a key role in the purine salvage pathway. Activated T cells seem to rely heavily on PNP to remain functionally active and are particularly sensitive to PNP deficiency. The role of PNP in periodontal tissues has not been characterized thus far. The aim of this study therefore was to assess the activity and expression of PNP in the gingival tissues of periodontitis patients. MATERIAL AND METHODS: Ten patients consecutively admitted for treatment had their periodontal clinical variables recorded and their gingival crevicular fluid collected. After periodontal treatment the patients were seen once a month for plaque and bleeding control, and had their periodontal variables recorded and gingival crevicular fluid collected at 90 and 180 d. Purine nucleoside phosphorylase-specific activity was assessed using a spectrophotometer through the addition of the PNP substrate analog 2-amino-6mercapto-7-methyl purine riboside to the gingival crevicular fluid. In parallel, PNP expression was assessed by immunohistochemistry and real time PCR in gingival biopsies and cell culture. RESULTS: Purine nucleoside phosphorylase activity was higher in the gingival crevicular fluid of periodontally diseased sites, which was positively correlated with improvements of the clinical variables. Treatment of periodontal disease induced a striking decrease of PNP activity in periodontally diseased sites. Expression of PNP was more pronounced in mononuclear cells and endothelial cells of the gingiva, and the mRNA levels were 5.7-fold higher in inflamed tissues compared with control samples. CONCLUSION: Purine nucleoside phosphorylase activity and expression are upregulated in periodontally diseased sites and can be detected in the gingival crevicular fluid. PMID- 20572922 TI - Trypsin-like protease-active extracellular protein extracts from Porphyromonas gingivalis ATCC 33277 induce apoptosis in bovine aortic endothelial cells. AB - BACKGROUND AND OBJECTIVE: Certain virulence factors participating in periodontitis may relate to cardiovascular diseases. This study was to evaluate the pro-apoptotic effect of protein extracts from Porphyromonas gingivalis on bovine aortic endothelial cells (BAECs). MATERIAL AND METHODS: The BAECs were exposed to trypsin-like protease-active protein extracts from P. gingivalis, and apoptosis was examined by Hoechst 33342 staining, DNA fragmentation assay and cleaved caspase-3 detection. When BAECs were exposed to protein extracts pretreated with trypsin-like protease inhibitor (TLCK), the apoptosis rate was evaluated by Annexin V-propidium iodide staining. To further study the potential mechanism of the pro-apoptotic effect, immunoblotting was used to detect expression of alpha-tubulin, integrin beta1 and activated ERK1/2 in BAECs treated with protein extracts or cultured in suspension. RESULTS: After exposure to the protein extracts, BAECs exhibited loss of cell adhesion and apoptotic cell death. The pro-apoptotic effect could be delayed by TLCK pretreatment. In addition, BAECs treated with protein extracts showed decreased levels of alpha-tubulin, integrin beta1 and activated ERK1/2. When BAECs were cultured in suspension, ERK1/2 activation was also inhibited, but the percentage decrease in ERK1/2 activation was less than that induced by protein extracts. Moreover, no significantly altered expression of alpha-tubulin was detected in suspended cells. CONCLUSION: Trypsin-like protease-active protein extracts from P. gingivalis could induce apoptosis of BAECs. The destruction of alpha-tubulin and integrin beta1 and decrease of ERK1/2 activation might contribute to the pro apoptotic effect of the protein extracts. PMID- 20572923 TI - Cytodifferentiation activity of synthetic human enamel sheath protein peptides. AB - BACKGROUND AND OBJECTIVE: Enamel sheath protein (ESP) is involved in the construction of the enamel sheath during tooth development. The 17 kDa ESP is a one-step cleavage product processed by proteolysis from the N-terminal side of sheathlin (ameloblastin/amelin), one of the porcine enamel matrix proteins. Enamel sheath protein exhibits periodontal ligament and cementum regeneration activity in a buccal dehiscence model in dogs, and promotes the cytodifferentiation of cultured human periodontal ligament (HPDL) cells. The aim of this study was to determine the peptide segment on the C-terminal side sequence of the human ESP that possesses a cytodifferentiation activity on cultured HPDL cells. MATERIAL AND METHODS: The peptides synthesized on the basis of human ESP C-terminal side sequence were tested for their ability to increase the alkaline phosphatase (ALP) and mineralization activity of cultured HPDL cells. The expressions of osteocalcin, osteopontin and bone sialoprotein were measured by semi-quantitative PCR and therefore were determined to be specific indicators of mineralized tissue differentiation. RESULTS: Multiple synthetic peptides from the human ESP increased the ALP activity and stimulated matrix mineralization in long-term cultures of HPDL cells. Semi-quantitative PCR demonstrated the osteocalcin, osteopontin and bone sialoprotein expressions to increase relative to the control values. The peptide SDKPPKPELPGVDF had the strongest cytodifferentiation activity among all the synthetic peptides tested. CONCLUSION: A specific peptide sequence derived from the C-terminal side of the human ESP promotes the cytodifferentiation and mineralization activity of HPDL cells in a cell culture system. PMID- 20572924 TI - In vitro antiherpes effects of a C-glycosylflavonoid-enriched fraction of Cecropia glaziovii Sneth. AB - AIMS: To investigate the in vitro antiherpes effects of the crude aqueous extract obtained from Cecropia glaziovii leaves and their related fractions, the n butanol fraction (n-BuOH) and the C-glycosylflavonoid-enriched fraction (MeOH(AMB)), and to determine the viral multiplication step(s) upon which this C glycosylflavonoid-enriched fraction acts. METHODS AND RESULTS: The antiviral activity was evaluated against human herpes virus types 1 and 2 (HHV-1, HHV-2) by plaque reduction assay. The mode of action of the most active fraction was investigated by a set of assays, and the results demonstrated that MeOH(AMB) fraction exerts anti-herpes action by the reduction of viral infectivity (only against HHV-2); by the inhibition of virus entry into cells; by the inhibition of cell-to-cell virus spread as well as by the impaired levels of envelope proteins of HHV-1. The high-performance liquid chromatography (HPLC)-photo-diode array (PDA) analysis showed that the C-glycosylflavonoids are the major constituents of this fraction. CONCLUSIONS: These data showed that the MeOH(AMB) fraction has an antiviral activity against HHV types 1 and 2. The C-glycosylflavonoids are the major constituents of this fraction, which suggests that they could be one of the compounds responsible for the detected anti-herpes activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The MeOH(AMB) fraction can be regarded as a phytopharmaceutical candidate for the treatment of herpetic infections. PMID- 20572925 TI - Dietary behaviour, food and nutrient intake of pregnant women in a rural community in Burkina Faso. AB - The aim of this study was to assess potential changes in dietary habits during pregnancy in a rural community in Hounde district, Burkina Faso. In-depth interviews were performed on a random sample of 37 pregnant women in order to analyse specific perceptions and attitudes regarding food consumption during pregnancy. In addition to this, an interactive 24-h recall survey was used to compare the food intake of 218 pregnant and 176 non-pregnant women. The majority of interviewees reported dietary restrictions during pregnancy but no consistent pattern of avoided food types was found. Most of the mentioned 'forbidden' foods were in related to physical discomfort during gestation. Interviewees also admitted to ignoring culturally determined food prohibitions/prescriptions. No differences were observed in food intake, food choice and nutrient intake between the group of pregnant and non-pregnant women. During the third trimester of gestation women did not show any major differences in food and nutrient intake compared with women from the first/second trimester. The mean nutrient intakes were found to be insufficient compared with the recommended daily allowances, especially for pregnant women. In conclusion, pregnant women in this rural area of Burkina Faso do not seem to restrict their diet significantly during pregnancy. The additional nutritional requirements of pregnancy are not accounted for in their dietary practises. PMID- 20572926 TI - The impact of maternal negative affectivity on dietary patterns of 18-month-old children in the Norwegian Mother and Child Cohort Study. AB - Early dietary habits are formative for dietary habits later in life. Maternal personality might be an important factor in unhealthy feeding of children. The current study aims to assess the degree to which the personality trait of negative affectivity in mothers predicts their child's diet at age 18 months. This study is a part of the Norwegian Mother and Child Cohort Study conducted at the Norwegian Institute of Public Health. A total of 27 763 mothers completed 3 repeated assessments of negative affectivity before and after childbirth and of the child's diet when the child was 18 months old. Exploratory factor analysis was used to identify the dietary patterns, and structural equation modeling was used to investigate the relationship with negative affectivity adjusted for socio demographical variables. Exploratory factor analysis of a foods frequency questionnaire revealed two dietary patterns in the child, labeled unhealthy diet and wholesome diet. The unhealthy diet comprised foods rich in sugar and fat; the wholesome diet comprised foods rich in fibre, vitamins and minerals. Mothers high in negative affectivity were more inclined to feed their child an unhealthy diet. The results were adjusted for maternal age, years of education, relative income, marital status, number of children, having the child in daycare, maternal smoking, maternal body mass index, and child gender. This study shows that a maternal personality trait, negative affectivity, is related to feeding the child an unhealthy diet after controlling for key socio-demographic variables. PMID- 20572928 TI - Effects of socio-economic and behavioural factors on childhood malnutrition in Yemen. AB - This study examined the effects of socio-economic and behavioural factors on childhood malnutrition in Yemen. The three anthropometric indicators such as height-for-age, weight-for-height and weight-for-age are used to examine the nutritional status of children aged less 5 years in Yemen. The independent variables include background characteristics, behavioural risk factors and illness characteristics. Data for the study come the most recent Yemen Demographic and Health Survey, a nationally representative sample, conducted in Yemen in 1997. Logistic regression analysis is used to estimate the odds of being malnourished. The three anthropometric indicators show high to very high levels of child malnutrition in Yemen. The prevalence of stunting and underweight is so widespread that almost every other child under the age of 5 is either stunted or underweight. Social, economic and behavioural factors show very significant association with childhood malnutrition. The study results indicate the importance of social and behavioural factors in describing childhood malnutrition in Yemen. The study results will help develop nutritional and health promotion policies in order to improve childhood malnutrition in this country. PMID- 20572927 TI - Breastfeeding protects against adverse respiratory outcomes at 15 months of age. AB - The relationship between breastfeeding, respiratory and other allergic disorders has been controversial. Our aim was to investigate the relationships between breastfeeding, respiratory outcomes, eczema and atopy at 15 months of age in a prospective birth cohort in New Zealand. A total of 1105 children were enrolled at birth, and 1011 (91.2%) were followed up at 15 months. Logistic regression was used to model associations between breastfeeding duration and respiratory outcomes, eczema and atopy after adjusting for relevant confounding variables: ethnicity, socio-economic status, parity, body mass index, smoking in pregnancy, gender and respiratory infections in the first 3 months of life. Breastfeeding was associated with a significant reduction in the risk of adverse respiratory outcomes at 15 months. After adjustment for confounders, each month of exclusive breastfeeding reduced the risk of doctor-diagnosed asthma by 20% (odds ratio 0.80, 95% confidence interval 0.71 to 0.90), wheezing by 12% (0.88, 0.82 to 0.94) and inhaler use by 14% (0.86, 0.78 to 0.93). Associations for both exclusive and additional breastfeeding durations, and respiratory outcomes remained independently significant when modelled simultaneously. Although independently associated with all respiratory outcomes, adjusting for parental history of allergic disease or maternal history of asthma did not alter our findings. Breastfeeding was not associated with eczema or atopy at 15 months. In conclusion, there was a significant protective effect of breastfeeding on infant wheezing and other adverse respiratory outcomes that may be early indicators of asthma in New Zealand children. PMID- 20572929 TI - Inadequate feeding practices and impaired growth among children from subsistence farming households in Sidama, Southern Ethiopia. AB - Whether current child feeding practices and behaviours among rural households in Sidama, Southern Ethiopia conform to the World Health Organization (WHO) guiding principles for complementary feeding is uncertain. We assessed socio-demographic status, anthropometry, breastfeeding, complementary feeding practices and behaviours, and motor development milestones in a convenience sample of 97 breastfed children aged 6-23 months from three rural Sidama communities. Energy and nutrient intakes from complementary foods were also calculated from 1-day in home weighed records. Prevalence of stunting ranged from 25% for infants aged 6-8 months to 52% for children aged 12-23 months, whereas for wasting, the corresponding prevalence was 10% and 14%, respectively. Very few children were exclusively breastfed up to 6 months of age (n = 2), or received solids/semi solids for the recommended minimum number of times containing the recommended number of food groups. Responsive feeding was not practised and no cellular animal products were consumed. Median intakes of energy, and intakes and densities of micronutrients from complementary foods (but not protein) were below WHO recommendations, assuming average breast milk intakes; greatest shortfalls were for retinol, vitamin C and calcium densities. Mothers of stunted children were shorter and lighter, and from households of lower socio-economic status than non-stunted children (P < 0.05). Acquisition of some motor development milestones was delayed in stunted infants compared with their non-stunted counter-parts. In conclusion, interventions that address the WHO guiding principles for complementary feeding practices and behaviours, as well as prenatal influences on growth, are urgently required in this setting. PMID- 20572930 TI - Responses of tabanids to Nzi traps baited with octenol, cow urine and phenols in Canada. AB - Cow urine and the two phenols responsible for the attraction of biting flies to cow urine (4-methylphenol, 3-n-propylphenol) were compared with octenol (1-octen 3-ol) as baits for Tabanidae. Relative to an unbaited Nzi trap, catches of the horseflies Hybomitra lasiophthalma (Macquart), Tabanus similis Macquart and Tabanus quinquevittatus Wiedemann (Diptera: Tabanidae) were increased by 1.5-2.6, 1.4-2.0 and 1.4-1.9 times, respectively, whenever a bait included octenol released at either 0.13 mg/h or 1.5 mg/h, regardless of the presence of phenols or urine. Catches were not affected when traps were baited with phenols alone at evaporation rates of 0.38 mg/h (4-methylphenol) and 0.022 mg/h (3-n propylphenol). Catches of Hybomitra horseflies were increased by 1.5-1.9 times with cow urine and 2.6 times with cow urine + octenol. This bait combination could prove to be particularly useful for Hybomitra horseflies, the common tabanids of northern environments. PMID- 20572931 TI - Effect of architectural angularity on refugia selection by the brown spider, Loxosceles gaucho. AB - Some brown spider species infest man-made environments and pose a threat to human health. Because habitat architecture affects spider populations, I evaluated the preferences of individuals of Loxosceles gaucho (Gertsch) (Araneae: Sicariidae) for refugia with different angular structures. Four differently angled refugia models (acute-, right-, obtuse-angled and cylindrical) were placed on the litter of a forest fragment and observed each month for 1 year. Females of this species were found to prefer refugia with acute angles. This finding brings new information to our understanding of brown spider infestations in man-made environments: refugia with acute angles are likely to offer more protection for females and their offspring. PMID- 20572932 TI - Incrimination of the mosquito, Aedes taeniorhynchus, as the primary vector of heartworm, Dirofilaria immitis, in coastal Yucatan, Mexico. AB - Mosquito collections were carried out on microfilaraemic dogs, positive for Dirofilaria sp., for 18 consecutive nights in the coastal town of Celestun, Yucatan, southeast Mexico, during the rainy season (August) of 2007. A total of 292 female mosquitoes representing 12 species of dipteran Culicidae were collected: Anopheles albimanus (Wiedemann); Anopheles crucians (Wiedemann); Anopheles pseudopunctipennis (Theobald); Culex coronator (Dyar & Knab); Culex interrogator (Dyar & Knab); Culex nigripalpus (Theobald); Culex quinquefasciatus (Say); Culex salinarius (Coquillett); Aedes aegypti (Linnaeus); Aedes scapularis (Rondani); Aedes sollicitans (Walker), and Aedes taeniorhynchus (Wiedemann). Aedes taeniorhynchus and Cx. quinquefasciatus were the species found most commonly feeding on the dogs. Filarial nematodes were observed by microscopy in nine of the mosquito species collected; however, third-instar larvae were only observed in Ae. taeniorhynchus and An. crucians. Of 76 Ae. taeniorhynchus specimens found positive for Dirofilaria sp. by dissection, 14 were confirmed to be positive for Dirofilaria immitis (Leidy) by polymerase chain reaction (PCR). The resulting infection rate for D. immitis confirmed by PCR (6.2%) is higher than any infection rate for Ae. taeniorhynchus previously reported from the Americas. PMID- 20572933 TI - Genetic structure and population dynamics of the biting midges Culicoides obsoletus and Culicoides scoticus: implications for the transmission and maintenance of bluetongue. AB - Culicoides species belonging to the Obsoletus complex (Diptera: Ceratopogonidae) have been indicated as primary bluetongue (BT) vectors in many European countries and their possible involvement in the maintenance and overwintering of BT viruses has been suggested, even in regions where Culicoides imicola Keiffer is the main vector. The Obsoletus complex includes two predominant taxa, Culicoides obsoletus (Meigen) and Culicoides scoticus Downes & Kettle. However, the role played by each species in the epidemiology of BT is still unknown. Taxonomic identification is mainly based on the morphology of male genitalia and the lack of other reliable diagnostic features makes the screening of trap-collected vector populations, mainly females, particularly difficult. Although molecular markers have facilitated species identification, little information is yet available on the biology, abundance and population dynamics of the two taxa. The aim of this work was to investigate the genetic profile and temporal distribution of C. obsoletus and C. scoticus by using isozyme electrophoresis applied to adult midges, collected weekly at two selected farms in southern Sardinia. A total of nine enzyme loci were analysed and five of them provided diagnostic allozyme markers (Hk, Mdh, Pgi, Idh-1 and Idh-2). Nei's genetic distance between the two taxa was in the range of other well-separated taxa (D = 1.792), supporting their status as true species. Culicoides scoticus represented almost 61% of the 562 specimens analysed; its genetic structure was characterized by a very low level of intra-population variation (mean heterozygosity H(e) = 0.019) and higher genetic divergence between populations (F(ST) = 0.0016) than in C. obsoletus. The latter species had significantly more heterozygotes (H(e) = 0.123), a higher percentage of polymorphic loci, and no inter-population differentiation (F(ST) ? 0). We suggest that different biological and ecological constraints, such as breeding habitat requirements, may contribute to shaping the genetic profiles of C. scoticus and C. obsoletus. However, enough gene flow was maintained between populations of each species as no spatial and temporal structuring was sustained by Fisher's exact probability test (P > 0.5). The seasonal distributions of C. scoticus and C. obsoletus only partially overlapped: both species were mainly found early in the year, when the main vector, C. imicola, was present in low numbers, and peaked in abundance in April and May. Culicoides scoticus was predominant until May, decreased rapidly in the following months and increased again in winter, whereas C. obsoletus decreased more slowly and was still present in early summer. Consequently, C. scoticus may be a good candidate for playing a role in the transmission and maintenance of BT virus in Sardinia, as well as in other Mediterranean countries, during the months of late winter and early spring when the seroconversion of sentinel animals is still occurring in the absence of the main vector. PMID- 20572934 TI - Photorhabdus phase variants express a novel fimbrial locus, mad, essential for symbiosis. AB - Fimbriae are adhesive organelles known to enable pathogens to colonize animal tissue, but little is known of their function in mutualistic symbioses. Photorhabdus colonization of Heterorhabditis bacteriophora nematodes is essential for the pair's insect pathogenic lifestyle. Maternal nematodes acquire Photorhabdus symbionts as a persistent intestinal biofilm prior to transmission to infective juvenile (IJ) stage offspring developing inside the maternal body. Screening 8000 Photorhabdus mutants for defects in IJ colonization revealed that a single fimbrial locus, named mad for maternal adhesion defective, is essential. The mad genes encode a novel usher/chaperone assembled fimbria regulated by an ON/OFF invertible promoter switch. Adherent Photorhabdus cells in maternal nematode intestines had the switch ON opposite to the OFF orientation of most other cells. A DeltamadA mutant failed to adhere to maternal intestines and be transmitted to the IJs. Mad fimbriae were detected on TT01 phase ON cells but not on DeltamadA phase ON cells. Also required for transmission is madJ, predicted to encode a transcriptional activator related to GrlA. Expression of madA-K or madIJK restored the ability of madJ mutant to adhere. The Mad fimbriae were not required for insect pathogenesis, indicating the specialized function of Mad fimbriae for symbiosis. PMID- 20572935 TI - Functional amyloid in Pseudomonas. AB - Amyloids are highly abundant in many microbial biofilms and may play an important role in their architecture. Nevertheless, little is known of the amyloid proteins. We report the discovery of a novel functional amyloid expressed by a Pseudomonas strain of the P. fluorescens group. The amyloid protein was purified and the amyloid-like structure verified. Partial sequencing by MS/MS combined with full genomic sequencing of the Pseudomonas strain identified the gene coding for the major subunit of the amyloid fibril, termed fapC. FapC contains a thrice repeated motif that differs from those previously found in curli fimbrins and prion proteins. The lack of aromatic residues in the repeat shows that aromatic side chains are not needed for efficient amyloid formation. In contrast, glutamine and asparagine residues seem to play a major role in amyloid formation as these are highly conserved in curli, prion proteins and FapC. fapC is conserved in many Pseudomonas strains including the opportunistic pathogen P. aeruginosa and is situated in a conserved operon containing six genes, of which one encodes a fapC homologue. Heterologous expression of the fapA-F operon in Escherichia coli BL21(DE3) resulted in a highly aggregative phenotype, showing that the operon is involved in biofilm formation. PMID- 20572936 TI - Cell dispersal in biofilms: an extracellular DNA masks nature's strongest glue. AB - Growth in biofilms provides bacterial species with many advantages over growth in suspension, e.g. colonization of nutrient-rich areas. In the alpha proteobacterium Caulobacter crescentus biofilm formation is facilitated through its asymmetric cell division, where one daughter cell becomes a motile flagellated swarmer cell able to colonize new surfaces while the other remains as a stalked cell attached to the substrate through the adhesive holdfast. The Caulobacter biofilm consists of stalked cells arranged either in a monolayer or in a multicellular 'mushroom' structure. In this issue of Molecular Microbiology, Berne et al. demonstrate that extracellular DNA (eDNA) from lysed cells prevents biofilm maturation. eDNA masks the adhesive properties of newly synthesized holdfast to enable the escape of swarmer cells from the biofilm. By contrast, holdfasts on previously attached stalked cells remain unaffected by eDNA. Surprisingly, the inhibitory effect was genus-specific, as only DNA from Caulobacter, but not from other genera, could interfere with biofilm maturation. This study reveals a new role for DNA in biofilms, as a regulatory rather than a structural component, and a novel mechanism to facilitate the escape of cells from biofilms. A compelling case is made for the existence of a new type of genus specific 'macromolecular language'. PMID- 20572937 TI - The RNA degradosome in Bacillus subtilis: identification of CshA as the major RNA helicase in the multiprotein complex. AB - In most organisms, dedicated multiprotein complexes, called exosome or RNA degradosome, carry out RNA degradation and processing. In addition to varying exoribonucleases or endoribonucleases, most of these complexes contain a RNA helicase. In the Gram-positive bacterium Bacillus subtilis, a RNA degradosome has recently been described; however, no RNA helicase was identified. In this work, we tested the interaction of the four DEAD box RNA helicases encoded in the B. subtilis genome with the RNA degradosome components. One of these helicases, CshA, is able to interact with several of the degradosome proteins, i.e. RNase Y, the polynucleotide phosphorylase, and the glycolytic enzymes enolase and phosphofructokinase. The determination of in vivo protein-protein interactions revealed that CshA is indeed present in a complex with polynucleotide phosphorylase. CshA is composed of two RecA-like domains that are found in all DEAD box RNA helicases and a C-terminal domain that is present in some members of this protein family. An analysis of the contribution of the individual domains of CshA revealed that the C-terminal domain is crucial both for dimerization of CshA and for all interactions with components of the RNA degradosome, including RNase Y. A transfer of this domain to CshB allowed the resulting chimeric protein to interact with RNase Y suggesting that this domain confers interaction specificity. As a degradosome component, CshA is present in the cell in similar amounts under all conditions. Taken together, our results suggest that CshA is the functional equivalent of the RhlB helicase of the Escherichia coli RNA degradosome. PMID- 20572939 TI - Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor. AB - Lipoproteins are a distinct class of bacterial membrane proteins that are translocated across the cytoplasmic membrane primarily by the Sec general secretory pathway and then lipidated on a conserved cysteine by the enzyme lipoprotein diacylglycerol transferase (Lgt). The signal peptide is cleaved by lipoprotein signal peptidase (Lsp) to leave the lipid-modified cysteine at the N terminus of the mature lipoprotein. In all Gram-positive bacteria tested to date this pathway is non-essential and the lipid attaches the protein to the outer leaflet of the cytoplasmic membrane. Here we identify lipoproteins in the model Gram-positive bacterium Streptomyces coelicolor using bioinformatics coupled with proteomic and downstream analysis. We report that Streptomyces species translocate large numbers of lipoproteins out via the Tat (twin arginine translocase) pathway and we present evidence that lipoprotein biogenesis might be an essential pathway in S. coelicolor. This is the first analysis of lipoproteins and lipoprotein biogenesis in Streptomyces and provides the first evidence that lipoprotein biogenesis could be essential in a Gram-positive bacterium. This report also provides the first experimental evidence that Tat plays a major role in the translocation of lipoproteins in a specific bacterium. PMID- 20572938 TI - FfVel1 and FfLae1, components of a velvet-like complex in Fusarium fujikuroi, affect differentiation, secondary metabolism and virulence. AB - Besides industrially produced gibberellins (GAs), Fusarium fujikuroi is able to produce additional secondary metabolites such as the pigments bikaverin and neurosporaxanthin and the mycotoxins fumonisins and fusarin C. The global regulation of these biosynthetic pathways is only poorly understood. Recently, the velvet complex containing VeA and several other regulatory proteins was shown to be involved in global regulation of secondary metabolism and differentiation in Aspergillus nidulans. Here, we report on the characterization of two components of the F. fujikuroi velvet-like complex, FfVel1 and FfLae1. The gene encoding this first reported LaeA orthologue outside the class of Eurotiomycetidae is upregulated in DeltaFfvel1 microarray-studies and FfLae1 interacts with FfVel1 in the nucleus. Deletion of Ffvel1 and Fflae1 revealed for the first time that velvet can simultaneously act as positive (GAs, fumonisins and fusarin C) and negative (bikaverin) regulator of secondary metabolism, and that both components affect conidiation and virulence of F. fujikuroi. Furthermore, the velvet-like protein FfVel2 revealed similar functions regarding conidiation, secondary metabolism and virulence as FfVel1. Cross-genus complementation studies of velvet complex component mutants between Fusarium, Aspergillus and Penicillium support an ancient origin for this complex, which has undergone a divergence in specific functions mediating development and secondary metabolism. PMID- 20572943 TI - Letter from the Editor-in-Chief. PMID- 20572940 TI - H-NOX regulation of c-di-GMP metabolism and biofilm formation in Legionella pneumophila. AB - Haem Nitric oxide/OXygen (H-NOX) binding domains are a family of haemoprotein sensors that are widespread in bacterial genomes, but limited information is available on their function. Legionella pneumophila is the only prokaryote found, thus far, to encode two H-NOX proteins. This paper presents data supporting a role for one of the L. pneumophila H-NOXs in the regulation of biofilm formation. IN SUMMARY: (i) unmarked deletions in the hnox1 gene do not affect growth rate in liquid culture or replication in permissive macrophages; (ii) the Deltahnox1 strain displays a hyper-biofilm phenotype; (iii) the gene adjacent to hnox1 is a GGDEF-EAL protein, lpg1057, and overexpression in L. pneumophila of this protein, or the well-studied diguanylate cyclase, vca0956, results in a hyper-biofilm phenotype; (iv) the Lpg1057 protein displays diguanylate cyclase activity in vitro and this activity is inhibited by the Hnox1 protein in the Fe(II)-NO ligation state, but not the Fe(II) unligated state; and (v) consistent with the Hnox1 regulation of Lpg1057, unmarked deletions of lpg1057 in the Deltahnox1 background results in reversion of the hyper-biofilm phenotype back to wild-type biofilm levels. Taken together, these results suggest a role for hnox1 in regulating c-di-GMP production by lpg1057 and biofilm formation in response to NO. PMID- 20572941 TI - Stabilization of Clostridium perfringens collagenase mRNA by VR-RNA-dependent cleavage in 5' leader sequence. AB - The small RNA (sRNA), VR-RNA that is directly regulated by the VirR/VirS two component system, regulates many genes including toxin genes such as collagenase (colA) and phospholipase C (plc) in Clostridium perfringens. Although the VR-RNA 3' region is sufficient to regulate the colA and plc genes, the molecular mechanism of toxin gene regulation by VR-RNA remains unclear. Here, we found that colA mRNA is cleaved at position -79 and -78 from the A of the first codon (ATG) in the presence of VR-RNA. The processed transcripts were stable compared with longer intact transcripts. On the other hand, colA mRNA was labile in a VR-RNA deficient strain, and processed transcripts were undetectable. The stability and processing of colA mRNA were restored by transformation of the 3' region of VR RNA-expression vector. The 3' region of VR-RNA and colA mRNA had significant complementation and interacted in vitro. These results show that VR-RNA base pairs with colA mRNA and induces cleavage in the 5' untranslated region (UTR) of colA mRNA, which leads to the stabilization of colA mRNA and the activation of colA expression. PMID- 20572944 TI - Early signalling events in the Avr9/Cf-9-dependent plant defence response. AB - Abstract Resistance of tomato to the leaf mould fungus Cladosporium fulvum is controlled by the interaction between a plant-encoded resistance gene (Cf-9) and pathogen-encoded avirulence (Avr9) gene. Our objective is to understand the underlying molecular mechanisms that transmit the Cf-9/Avr9-dependent pathogen perception event and activate the plant defence response. Our approach toward the understanding of Cf-function is based on the analysis of early Cf-9/Avr9-mediated responses and signalling events. Because Cf-9 transgenically expressed in tobacco retains its specificity and activity to the Avr9 elicitor, signalling experiments were conducted in the heterologous system using these transgenic lines or derived Cf9 tobacco cell cultures. Among the earliest responses to the Avr9/Cf-9 elicitation event were rapid changes in ion-fluxes, the synthesis of active oxygen species (AOS), probably catalysed by a plant NADPH-oxidase, and the transient activation of two MAP kinases. These kinases were identified as WIPK (wounding-induced protein kinase) and SIPK (salicylic-acid induced kinase) from tobacco. Studies with pharmacological inhibitors suggested that the MAP kinases are located in an independent signalling pathway from the Avr9/Cf-9-dependent synthesis of AOS. SIPK and WIPK were involved in pathogen-related elicitation processes as well as in abiotic stress responses. This indicates that the plant defence is triggered via a signalling network that shares components with pathways originating from abiotic environmental stress stimuli. PMID- 20572945 TI - Programmed responses to virus replication in plants. AB - Abstract Despite their economic importance, we understand very little about the mechanism leading to symptom formation in compatible virus infections. By applying a spatial analysis to advancing infection fronts, we have been able to relate molecular events in small groups of cells to a sequence of virus-induced changes. This sequence starts ahead of the main front of virus replication and virus protein accumulation and lasts beyond the time at which virus replication has ceased. The host changes include alterations in gene expression, physiology and cellular ultrastructure. The relationship between these effects has been analysed in comparative studies between different virus infections in different hosts and abiotic stress. The research points to there being common features for different viruses leading to common effects. Also, although many of the consequences of virus infection are similar to the effects of heat shock, there are sufficient differences to suggest that the two inducers use distinct control pathways. The immediate challenge for the future is to establish synchronous infections of tissues so that the complex relationship between the virus and the host can be investigated using temporal rather than spatial analyses. PMID- 20572946 TI - Unravelling R gene-mediated disease resistance pathways in Arabidopsis. AB - Abstract Molecular genetic approaches were adopted in the model crucifer, Arabidopsis thaliana, to unravel components of RPP5- and RPP1-mediated disease resistance to the oomycete pathogen, Peronospora parasitica. The products of RPP5 and three genes comprising the RPP1 complex locus belong to a major subclass of nucleotide-binding/leucine-rich repeat (NB-LRR) resistance (R) protein that has amino-terminal homology to the cytoplasmic domains of Drosophila and mammalian Toll and interleukin-1 family receptors (the so called 'TIR' domain). Similarities in the domain architecture of these proteins and animal regulators of programmed cell death have also been observed. Mutational screens revealed a number of genes that are required for RPP5-conditioned resistance. Among these are EDS1 and PAD4. Both EDS1 and PAD4 precede the function of salicylic acid mediated plant responses. The EDS1 and PAD4 genes were cloned and found to encode proteins with similarity to the catalytic site of eukaryotic lipases, suggesting that they may function by hydrolysing a lipid-based substrate. PMID- 20572947 TI - Lipopolysaccharides and plant responses to phytopathogenic bacteria. AB - Abstract Treatment of the leaves of pepper (Capsicum annuum) cv. ECW10R with lipopolysaccharides (LPS) from both plant pathogenic and enteric bacteria alters several aspects of the plant response to subsequent inoculation with phytopathogenic xanthomonads. LPS pre-treatment prevents the hypersensitive reaction caused by strains of Xanthomonas campestris pv. vesicatoria carrying the avirulence gene avrBs1 (a gene-for-gene interaction) and by X. campestris pv. campestris (a non-host interaction). Associated with this effect are the earlier synthesis of feruloyl- and coumaroyl-tyramine, phenolic conjugates that are potentially antimicrobial, and alterations in the expression patterns of genes for some pathogenesis-related (PR) proteins. Similar effects on the timing of phenolic conjugate synthesis are also seen in the compatible interaction with X. campestris pv. vesicatoria, although the level of the response is lower. Recognition of LPS by plants may allow expression of resistance in the absence of catastrophic tissue damage. However phytopathogenic bacteria may have evolved mechanisms to suppress the effects of LPS (and of other non-specific bacterial elicitors) on plant cells. PMID- 20572948 TI - Cell-to-cell movement of tobacco mosaic virus: enigmas and explanations. AB - Abstract Tobacco mosaic virus (TMV) spreads between cells through plant intercellular connections, the plasmodesmata. This transport process is mediated by a specialized virus-encoded movement protein, TMV MP. Recent advances in two major aspects of TMV MP function highlight the limits of our current knowledge and promise exciting future developments. First, findings that TMV MP interacts with cytoskeletal elements and cell wall proteins suggest potential mechanisms for TMV MP targeting from the cell cytoplasm to plasmodesmal channels. Second, indications that TMV MP phosphorylation plays a regulatory role in several activities of TMV MP begin to unravel molecular pathways that control TMV cell-to cell transport. TMV systemic movement that follows its initial cell-to-cell spread, on the other hand, may be controlled through two different pathways used for viral entry into and exit from the host plant vascular tissue. PMID- 20572949 TI - Conditioning of cellular defence responses to powdery mildew in cereal leaves by prior attack. AB - Abstract Field-grown plants sequentially encounter many different fungal pathogens and nonpathogens that are capable of triggering an array of responses that may affect the subsequent level of disease they develop following later pathogen attack. These changes, which are induced by prior encounters, may be manifest as increased susceptibility or enhanced resistance to later pathogen attack; they may be expressed systemically or their effects may be localized within a few cells distance of the original encounter site. Here, we review our recent investigations of cellular changes effected by sequential inoculations of cereal leaves with the powdery mildew fungus Blumeria graminis DC. In susceptible barley and oats, a successful B. graminis attack followed by haustorium formation, renders the attacked cell, and to some extent its adjacent cells, highly accessible to later B. graminis attacks. By contrast, a failed attack due to papilla formation by the attacked host cells, renders the attacked cell and its adjacent cells highly inaccessible to later B. graminis attacks. Importantly, barley carrying the mlo5 allele for powdery mildew resistance is also conditioned to accessibility if prior attacks by an mlo-virulent isolate penetrates successfully. In the partial resistant oat cultivar Maldwyn B. graminis attacks either succeeded, failed due to papilla deposition, or failed because the attacked host cells died in response to the attacks. Sequential inoculation of Maldwyn demonstrated the induction of accessibility and inaccessibility, as well as a complete suppression of cell death response to attack where the cells had survived an earlier attack. Furthermore, when a prior attack induced cell death, a later attack on adjacent cells caused greatly increased rate of cell death, demonstrating potentiation of cell death. The importance of the induced cellular changes for plant resistance in the field is discussed. PMID- 20572950 TI - Regulation of carbohydrate partitioning during the interaction of potato virus Y with tobacco. AB - Abstract To test whether carbohydrates may play a signalling function during plant pathogenesis, we investigated the interaction between tobacco and potato virus Y (PVY(N)). Four days after PVY(N) infection, leaves started to accumulate soluble sugars and leaf photosynthesis decreased. The accumulation of soluble sugars was accompanied by an induction of cell wall invertase and a gradual decrease in the sucrose-to-hexose ratio. In parallel to changes in carbohydrate metabolism and photosynthesis, transcripts encoding PR-proteins accumulated. Based on this coincidence, it was hypothesized that elevated hexose levels may enhance the expression of defence-related functions and might possibly explain the phenomenon of high sugar resistance in plants. This notion has been supported by the fact that cell wall invertase-expressing transgenic tobacco plants were found to be resistant against PVY(N) (Herbers et al., 1996b). To exclude the possibility that salicylate, which accumulates in plants expressing invertase, may be responsible for the observed resistance, these transgenic plants were crossed with salicylate hydroxylase-expressing plants (nahG). The progeny were selected for high levels of sugar and low levels of salicylate. Necrotic lesions also developed, typically formed on the leaves of plants expressing invertase, and transcripts encoding PR-Q accumulated in the absence of salicylate. On the other hand, accumulation of PR-1b transcripts decreased, indicating that sugars are not sufficient for PR-1b induction. Infection experiments using these plants as hosts revealed resistance towards PVY(N). Thus, the mechanism of apoplastic invertase induced virus resistance is salicylate independent and most likely sugar mediated. PMID- 20572951 TI - Regulation of pathogenic development in the corn smut fungus Ustilago maydis. AB - Abstract In Ustilago maydis, the b mating type locus constitutes the central regulatory domain for pathogenic development. The b locus encodes two homeodomain proteins that are thought to function as transcriptional regulators. Here we describe our current view of the different regulatory pathways in which the b locus is involved. We emphasize on the development of tools for the isolation of genes that are directly regulated by b homeodomain proteins. PMID- 20572952 TI - Plant signalling and induced defence in insect attack. AB - Abstract Plants can produce compounds which act as semiochemicals, that is, signals modifying the development or behaviour of other organisms without having direct physiological activity. Among such semiochemicals are plant stress signals associated with the induction of defence systems, and these may include phytopheromones that naturally influence plant development. It is well known that plant-derived semiochemicals can be exploited by colonizing organisms, particularly pathogens and insect pests. Recently proposed external signals not yet proven as natural phytopheromones are nitric oxide and the volatile methyl esters of jasmonic and salicylic acids. Since it is now possible to use sophisticated electrophysiological techniques to investigate insect interactions with prospective phytopheromones, the detection and characterization of signalling systems has been made much easier and can provide a molecular characterization of signals that are active beyond the insects themselves. In addition to the advances these studies have brought to the understanding of plant/insect and plant/plant interactions, plant signals are potentially valuable in the regulation of gene expression for improved or alternative approaches to crop protection or for other developmental processes in plants. PMID- 20572953 TI - How the bacterial plant pathogen Xanthomonas campestris pv. vesicatoria conquers the host. AB - Abstract Xanthomonas campestris pv. vesicatoria (Xcv) is the causal agent of bacterial spot disease on pepper and tomato. Pathogenicity on susceptible plants and the induction of the hypersensitive reaction (HR) on resistant plants requires a number of genes, designated hrp, most of which are clustered in a 23 kb chromosomal region. Nine hrp genes encode components of a type III protein secretion apparatus that is conserved in Gram-negative plant and animal pathogenic bacteria. We have recently demonstrated that Xcv secretes proteins into the culture medium in a hrp-dependent manner. Substrates of the Hrp secretion machinery are pathogenicity factors and avirulence proteins, e.g. AvrBs3. The AvrBs3 protein governs recognition, i.e. HR induction, when bacteria infect pepper plants carrying the corresponding resistance gene Bs3. Intriguingly, the AvrBs3 protein contains eukaryotic signatures such as nuclear localization signals (NLS), and has been shown to act inside the plant cell. We postulate that AvrBs3 is transferred into the plant cell via the Hrp type III pathway and that recognition of AvrBs3 takes place in the plant cell nucleus. PMID- 20572954 TI - Pararetrovirus-crucifer interactions: attack and defence or modus vivendi? AB - Abstract The compatible infection of plants by viruses usually leads to the development of systemic symptoms. Symptom expression of this kind is generally understood to be a host response that indicates an inability of the host to defend itself from attack. We have been studying compatible interactions between the plant pararetrovirus cauliflower mosaic virus (CaMV) and its crucifer hosts in order to understand the relationship between viral activity, symptom expression and plant defence. A CaMV protein (P6) appears to play a major role in eliciting symptom expression. This host response leads to a regulation of the viral multiplication cycle that is associated with leaf mosaics. The host regulation of CaMV appears to operate at the transcriptional level through an effect on the 35S promoter, or at the post-transcriptional level by a process that is akin to gene silencing, and can lead to host recovery depending upon the genetic background of the host. The plant apex is a focus for antiviral defence mechanisms, presumably because viral infection of the apical meristem would rapidly compromise the ability of the plant to generate new leaves and flowers for reproduction. The balance of interactions between CaMV and crucifers can provide a sustainable source of host plants to ensure viral propagation and viral exposure allows the host to adapt and develop its repertoire of defence mechanisms. PMID- 20572955 TI - DNA and protein transfer from bacteria to eukaryotes- the agrobacterium story. AB - Abstract Agrobacterium is a well-studied plant pathogen, which has the unique ability to transfer DNA and protein into a number of eukaryotes. The DNA is integrated randomly into the plant genome where it is expressed, thereby leading to the disease crown gall. This system is a paradigm for the interaction of a number of plant and animal pathogens which transfer proteins into their host cells. In Agrobacterium, the tumour inducing (Ti) plasmid codes for the functions specifically required for the transfer process. These genes, termed virulence or vir genes, are activated by plant signal molecules acting through a two component regulatory system. A key structure coded by 11 genes of the vir B operon is a pilus, synthesized at 20 degrees C, but poorly at 25 degrees C. How this pilus functions in DNA and protein transfer is unclear, but homologous genes are found in many animal pathogens. In addition to Ti plasmid-encoded vir genes, chromosomal virulence genes have also been identified. However, these mutations are often pleiotropic because they involve both the normal physiology of Agrobacterium as well as the metabolism of Agrobacterium when it is associated with plant cells. Based on 16S ribosomal RNA sequencing, Agrobacterium is closely related to the intracellular pathogen of animals, Brucella. Several chromosomal mutations of Agrobacterium required for virulence in plants are also required for invasion of animal host cells by Brucella. PMID- 20572956 TI - Brome mosaic virus, good for an RNA virologist's basic needs. AB - Abstract Taxonomic relationship: Type member of the Bromovirus genus, family Bromoviridae. A member of the alphavirus-like supergroup of positive-sense single stranded RNA viruses. Physical properties: Virions are nonenveloped icosahedrals made up of 180 coat protein subunits (Fig. 1). The particles are 26 nm in diameter and contain 22% nucleic acid and 78% protein. The BMV genome is composed of three positive-sense, capped RNAs: RNA1 (3.2 kb), RNA2 (2.9 kb), RNA3 (2.1 kb) (Fig. 2). Viral proteins: RNA1 encodes protein 1a, containing capping and putative RNA helicase activities. RNA2 encodes protein 2a, a putative RNA dependent RNA polymerase. RNA3 codes for two proteins: 3a, which is required for cell-to-cell movement, and the capsid protein. The capsid is translated from a subgenomic RNA, RNA4 (1.2 kb). Hosts: Monocots in the Poacea family, including Bromus inermis, Zea mays and Hordeum vulgare, in which BMV causes brown streaks. BMV can also infect the dicots Nicotiana benthamiana and several Chenopodium species. In N. benthamiana, the infection is asymptomatic while infection of Chenopodium can cause either necrotic or chlorotic lesions. Useful website:http://www4.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/10030001.htm. PMID- 20572957 TI - Infection of Arabidopsis thaliana leaves with Albugo candida (white blister rust) causes a reprogramming of host metabolism. AB - Abstract Albugo candida (Pers.) (O.) Kunze is a biotrophic pathogen which infects the crucifer Arabidopsis thaliana (L.) Heynh forming discrete areas of infection. Eight days after inoculation of leaves, white blisters became visible on the under surface of the leaf although no symptoms were apparent on the upper surface. By day 14, the region of leaf invaded by fungal mycelium had become chlorotic. Recently it has been hypothesized that an accumulation of soluble carbohydrates, following an increase in invertase activity, may trigger sugar signal transduction pathways leading to the repression of photosynthetic gene expression and to the induction of defence proteins. This hypothesis was investigated by quantifying localized changes in carbohydrate and photosynthetic metabolism and the expression of genes encoding photosynthetic and defence proteins. Quantitative imaging of chlorophyll fluorescence revealed that the rate of photosynthesis declined progressively in the invaded regions of the leaf. However, in uninfected regions of the infected leaf the rate of photosynthesis was similar to that measured in the control leaf until late on during the infection cycle when it declined. Images of nonphotochemical fluorescence quenching (NPQ) suggested that the capacity of the Calvin cycle had been reduced in infected regions and that there was a complex metabolic heterogeneity within the infected leaf. A. candida also caused localized changes in the carbohydrate metabolism of the leaf; soluble carbohydrates accumulated in the infected region whereas the amount of starch declined. The reverse was seen in uninfected regions of the infected leaf; carbohydrates did not accumulate until late on during infection and the amount of starch increased as the infection progressed. There was an increase in the activity of invertases which was confined to regions of the leaf invaded by the fungal mycelium. The increase in apoplastic invertase activity was of host origin, as mRNA levels of the ATbetaFRUCT1 gene (measured by semiquantitative RT-PCR) increased 40-fold in the infected region. The increase in soluble invertase activity resulted from the appearance of a new isoform in the invaded region of the leaf. Current evidence suggests that this was of fungal origin. Northern blot analysis of cab and rbcS showed that photosynthetic gene expression was repressed in the infected leaf from 6 days after inoculation (DAI) when compared to control leaves. In contrast, there was no detectable induction of defence proteins in the infected leaf. These data are discussed in the context of the sugar-sensing hypothesis presented above. PMID- 20572958 TI - Cell-specific expression of salicylate hydroxylase in an attempt to separate localized HR and systemic signalling establishing SAR in tobacco. AB - Abstract There is conflicting evidence concerning the nature of the long-distance signal responsible for establishing the systemic acquired resistance (SAR) state following a local response to an incompatible plant/pathogen interaction. We outline standard inoculation procedures and terminology for experiments used to characterize SAR in Nicotiana tabacum and show that leaf development (age) has dramatic affects on TMV lesion size which needs to be taken into account in experimental design. TMV infection was more efficient at inducing SAR than primary infection with avirulent bacteria. We have examined the effect on SAR induction of altering the accumulation of salicylic acid (SA), through the expression of a salicylate hydroxylase gene (SH-L), in different phases of lesion development using the hydrogen peroxide-responsive AoPR1 promoter and the salicylate-responsive PR1a promoter. Suppression of SA accumulation during the early phases of lesion development in AoPR1-SH-L transgenic tobacco resulted in an attenuated form of SAR compared to wild-type plants, whereas SAR was not exhibited in PR1a-SH-L plants. However, interpretation of data from these experiments was complicated by virus escape from inoculated leaves. Using a GUS reporter it was discovered that the CaMV35S promoter was not expressed constitutively in all cell types of petioles and stems, particularly phloem tissue, whereas the PR1a promoter demonstrated induced expression in the phloem following TMV infection. We suggest two hypotheses for why PR1a-SH-L transgenics do not display SAR: either the systemic expression of PR1a-SH-L is sufficient to suppress SAR, or SA synthesis or translocation in the phloem is essential for SAR. PMID- 20572959 TI - Differential expression of two Blumeria graminis chitin synthase genes. AB - Abstract Two Blumeria graminis chitin synthase genes, designated BgChs1 and BgChs2 were cloned and characterized following the synthesis and use of degenerate PCR primers designed to the conserved regions of fungal chitin synthase (Chs) genes. Their sequences revealed high similarity with the Chs genes previously cloned from other fungi and placed BgChs1 and BgChs2 with the classes I and V, respectively. Each gene was present as a single copy within the barley powdery mildew genome. Semi-quantitative RT-PCR assays revealed BgChs1 to be up regulated at both the primary germ tube (PGT) and appressorial germ tube (AGT) stages of differentiation whilst the BgChs2 transcript was up-regulated at the PGT stage. The B. graminisbeta-tubulin gene was used as a control for all RT-PCR reactions. The BgChs1 transcript was some 30 fold less abundant than the beta tubulin transcript and BgChs2 was some 30 fold rarer than the BgChs1 transcript. The effects of the chitin substrate analogues nikkomycin Z and polyoxin D on conidial morphogenesis were assessed. These nucleoside peptide inhibitors did not affect germination but both polyoxin D and nikkomycin Z treatment led to a large population of abnormally swollen 'balloon-shaped' AGTs, whilst by 12 h after inoculation polyoxin treatment caused the swollen germ tubes to burst. PMID- 20572960 TI - A dsbA mutant of Pseudomonas syringae exhibits reduced virulence and partial impairment of type III secretion. AB - Abstract To identify virulence genes of P. syringae pv. tomato strain DC3000 we screened for mutants with reduced virulence on its plant hosts, Arabidopsis thaliana and tomato. We isolated a Tn5-insertion mutant that exhibited reduced virulence on both hosts. Further characterization showed that this mutant carried a single Tn5 insertion in the dsbA gene, which encodes a periplasmic disulphide bond-forming protein. In addition to reduced virulence, the dsbA mutant exhibits mucoid colony morphology, loss of fluorescence, decreased motility, and a reduced growth rate in culture. The dsbA mutant is able to multiply in A. thaliana and tomato plants, trigger the hypersensitive response on tobacco and elicit Pto mediated resistance in tomato, indicating that type III secretion occurs in this background. However, type III secretion appears to function with reduced efficiency in the dsbA mutant, as type III-dependent secretion of HrpZ and AvrRpt2 is impaired. These findings indicate that while the dsbA gene is required for multiple cellular functions in P. syringae, type III secretion in P. syringae is only partially dependent on dsbA. PMID- 20572961 TI - Tomato spotted wilt virus-positive steps towards negative success. AB - Abstract Taxonomy: Tomato spotted wilt virus (TSWV) is the type member of the plant-infecting Tospovirus genus in the family Bunyaviridae, a large group of predominantly vertebrate- and insect-infecting RNA viruses. Physical properties: Virions are 80-120-nm pleomorphic particles with surface projections composed of two viral glycoproteins, G1 and G2 (Fig. 1). Virion composition is 5% nucleic acid, 70% protein, 5% carbohydrate and 20% lipid. The genome consists of three negative or ambisense ssRNAs designated S (2.9 kb), M (4.8 kb) and L (8.9 kb), with partially complementary terminal sequences that allow the RNA to adopt a pseudocircular or panhandle conformation. Each genomic RNA is encapsidated by multiple copies of the viral nucleocapsid (N) protein to form ribonucleoprotein structures also known as nucleocapsids. The nucleocapsids are enclosed in a host derived membrane bilayer along with an estimated 10-20 copies of the L protein, the putative RNA-dependent RNA polymerase. Hosts: Over 800 plant species, both dicots and monocots, in more than 80 plant families are susceptible to TSWV (Goldbach and Peters, 1994). The Solanaceae and Compositae families contain the largest numbers of susceptible plant species (Prins and Kormelink, 1998). TSWV also replicates in its insect vector, thrips (Thysanoptera: Thripidae) (Ullman et al., 1993; Wijkamp et al., 1993). Useful web site: http://www4.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/11050003.htm. PMID- 20572962 TI - A comparison between virus replication and abiotic stress (heat) as modifiers of host gene expression in pea. AB - Abstract Pea embryonic tissues respond to active replication of pea seed-borne mosaic potyvirus (PSbMV) by the down-regulation of a range of genes and the induction of others. Both of these responses can be seen when tissues are subjected to abiotic stress, particularly heat. We have compared the effects of the two inducers to assess whether the host alterations following virus replication represent generic responses to stress, or more specific effects. Five classes of response were identified: (i) genes induced by both stresses (e.g. heat shock protein 70, hsp70); (ii) genes induced by virus replication but unaffected by heat (e.g. glutathione reductase 2, gor2); (iii) genes induced by heat but unaffected by virus replication (e.g. heat shock factor, hsf); (iv) genes down-regulated by virus replication and unaffected by heat (e.g. vicilin, vic); and (v) genes unaffected by both inducers (e.g. actin, act and beta tubulin, tub). A change in the appearance and organization of the endoplasmic reticulum (ER) was also seen in cells actively replicating PSbMV RNA. Heat treatment of pea embryonic tissues also produced altered ER, although the changes were different from those seen following virus infection. Collectively, these data show that, while there are some common features of the responses to virus infection and heat, there are also substantial differences. Hence, it appears that the host response to virus replication is not a general stress response. PMID- 20572963 TI - Cloning and characterization of a glutathione S-transferase homologue from the plant pathogenic fungus Botrytis cinereadouble dagger. AB - Abstract A gene was cloned from Botrytis cinerea that encodes a protein homologous to glutathione S-transferase (GST). The gene, denominated Bcgst1, is present in a single copy and represents the first example of such a gene from a filamentous fungus. The biochemical function of GSTs is to conjugate toxic compounds to glutathione, thereby detoxifying the compound. In many other organisms, GST plays a role in chemical stress tolerance. We anticipated that GST functions for B. cinerea as a potential virulence factor, enabling the fungus to tolerate fungitoxic plant defence compounds. The expression of Bcgst1 mRNA under various presumably stressful conditions was investigated. Bcgst1 mRNA is expressed at a basal level in liquid cultures and is induced upon addition of hydrogen peroxide to the medium. The level of Bcgst1 mRNA expression during infection of tomato leaves parallels the level of actin mRNA. The role of the Bcgst1 gene in the virulence of Botrytis cinerea was evaluated by constructing gene disruption mutants. Three independent disruption mutants were obtained. The virulence of two mutants on tomato leaves was evaluated. Neither of the mutants showed a decrease in virulence, indicating that the Bcgst1 gene is not essential for virulence on tomato leaves under the conditions tested. PMID- 20572964 TI - Ralstonia solanacearum AmpD is required for wild-type bacterial wilt virulence. AB - Abstract A gene resembling enterobacterial ampD was identified in the bacterial wilt pathogen, Ralstonia solanacearum. The gene lies 13 bp 3' of pehSR, a two component positive regulator of virulence factors such as plant cell wall degrading polygalacturonases and bacterial motility. AmpD, an N-acetylmuramyl-l alanine amidase, degrades and recycles bacterial cell wall components and also plays a role in the induction of beta-lactamase, which confers ampicillin resistance. AmpD is probably not involved in beta-lactamase regulation in R. solanacearum, because the species produces no detectable beta-lactamase activity and is not ampicillin resistant. However, the R. solanacearum ampD gene restores inducible beta-lactamase activity to an Escherichia coli ampD mutant, demonstrating that the gene encodes an AmpD protein that can function in a heterologous background. An R. solanacearumampD chromosomal mutant was motile, produced wild-type levels of polygalacturonase activity and had wild-type cell and colony morphology. This mutant also grew normally in minimal medium and in plant tissue. Nonetheless, the ampD mutant was significantly reduced in bacterial wilt virulence on eggplant and tomato, suggesting a previously unsuspected role for N-acetylmuramyl-l-alanine amidase in plant pathogenesis. PMID- 20572965 TI - Molecular characterization of Fusarium subglutinans associated with mango malformation. AB - Abstract Mango malformation is a serious disease of Mangifera indica in tropical and subtropical regions of the world. This disease is caused by Fusarium subglutinans, which is also associated with diseases on many other hosts, such as pineapple, pine, maize and sugarcane. The F. subglutinans strains associated with different hosts are virtually indistinguishable using morphological characters, but can be easily differentiated using histone and beta-tubulin gene sequencing, and some have subsequently been assigned to distinct species. The aim of this study was to characterize F. subglutinans isolates associated with mango malformation using histone H3 gene sequencing and to compare them with other isolates in the Gibberella fujikuroi complex. Analysis of histone sequence data revealed the presence of two phylogenetically distinct groups of F. subglutinans isolates associated with mango malformation. We also considered the identity of the two groups of isolates associated with mango malformation and determined their relatedness to other Fusarium spp. For this purpose, portions of the beta tubulin gene were sequenced and compared with the beta-tubulin sequences deposited in the National Center for Biotechnology Information (NCBI) nucleotide database. This comparison to the NCBI database indicated that one group of F. subglutinans strains isolated from mango constitutes a unique lineage in the G. fujikuroi complex. Based on beta-tubulin and histone H3 sequencing, the second group of isolates is conspecific with the F. subglutinans strains previously reported to be the causal agent of mango malformation. PMID- 20572966 TI - Evidence for the mobility of an avirulence gene, avrPpiA1, between the chromosome and plasmids of races of Pseudomonas syringae pv. pisi. AB - Abstract An 8.5-kb DNA fragment containing the avirulence gene avrPpiA1 is present in the chromosome of race 2 but not present in race 4B of Pseudomonas syringae pv. pisi. The likely acquisition of avrPpiA1 in race 2 at some time in the past was indicated by the presence of direct repeat sequences at the boundaries of the 8.5-kb region, which was amplified by polymerase chain reaction (PCR), cloned and sequenced. The sequence analysis of the 8.5-kb fragment revealed the presence of rulAB genes, which are usually associated with plasmids. The rulB gene had been disrupted by a 4.3-kb length of DNA, which included avrPpiA1 and open reading frames (ORFs) with similarity to bacteriophage and transposase genes. Inverted repeats flanked the 4.3-kb region reinforcing the possibility that a further insertion had occurred in this region. The results presented here provide evidence for the horizontal transfer of an avirulence gene and suggest that this region may be a hotspot for recombination with the chromosome. PMID- 20572967 TI - From host recognition to T-DNA integration: the function of bacterial and plant genes in the Agrobacterium-plant cell interaction. AB - Abstract Agrobacterium tumefaciens and its related species, A. rhizogenes and A. vitis, are the only known bacterial pathogens which 'genetically invade' host plants and stably integrate part of their genetic material into the host cell genome. Thus, A. tumefaciens has evolved as a major tool for plant genetic engineering. Furthermore, this unique process of interkingdom DNA transfer has been utilized as a model system for studies of its underlying biological events, such as intercellular signalling, cell-to-cell DNA transport, protein and DNA nuclear import and integration. To date, numerous bacterial proteins and several plant proteins have been implicated in the A. tumefaciens-plant cell interaction. Here, we discuss the molecular interactions among these bacterial and plant factors and their role in the A. tumefaciens-plant cell DNA transfer. Taxonomic relationship: Bacteria; Proteobacteria; alpha subdivision; Rhizobiaceae group; Rhizobiaceae family; Agrobacterium genus. Microbiological properties: Gram negative, nonsporing, motile, rod-shaped, soil-borne. Related species:A. rhizogenes (causes root formation in infected plants), A. vitis (causes gall formation on grapevines). Disease symptoms: Formation of neoplastic swellings (galls) on plant roots, crowns, trunks and canes. Galls interfere with water and nutrient flow in the plants, and seriously infected plants suffer from weak, stunted growth and low productivity. HOST RANGE: One of the widest host ranges known among plant pathogens; can potentially attack all dicotyledonous plant species. Also, under controlled conditions (usually in tissue culture), can infect, albeit with lower efficiency, several monocotyledonous species. Agronomic importance: The disease currently affects plants belonging to the rose family, e.g. apple, pear, peach, cherry, almond, roses, as well as poplar trees (aspen). Useful web site:http://www.bio.purdue.edu/courses/gelvinweb/gelvin.html. PMID- 20572968 TI - The distribution and expression of a biotrophy-related gene, CIH1, within the genus Colletotrichum. AB - Abstract During the biotrophic phase of the infection process of the hemibiotrophic anthracnose fungus Colletotrichum lindemuthianum, an intracellular hypha develops within epidermal cells of its host, Phaseolus vulgaris. This is followed by the formation of secondary hyphae during the necrotrophic phase. Previous work using a monoclonal antibody, UB25, has identified a glycoprotein that is specific to the interfacial matrix that forms between the wall of the intracellular hypha and the invaginated host plasma membrane. The gene encoding the protein identified by UB25 was cloned by immunoscreening and designated CIH1. The predicted amino acid sequence revealed a proline-rich glycoprotein, and biochemical evidence suggested that it formed a cross-linked structure at the biotrophic interface. Although CIH1 is a fungal gene, its product has several similarities to plant cell wall proteins. In this paper, we have surveyed the distribution and expression of CIH1 within the genus Colletotrichum, encompassing both necrotrophic and hemibiotrophic species. The results show that homologues of the CIH1 gene are present in all the Colletotrichum species tested. Northern blot studies of the time course of the infection process in planta have shown that CIH1 is expressed by both C. lindemuthianum in bean and C. trifolii in alfalfa during the biotrophic phase of fungal development. Immunofluorescence labelling of infected epidermal strips with UB25 revealed that the intracellular hyphae formed by C. destructivum as it infects alfalfa were specifically labelled in a similar way to those formed by C. lindemuthianum in bean. Northern and Western analysis showed that CIH1 was also expressed by C. lindemuthianum in vitro, though not constitutively. Overall, the evidence supports a role for CIH1 in biotrophy within the genus Colletotrichum. PMID- 20572969 TI - Expression of the Shpx2 peroxidase gene of Stylosanthes humilis in transgenic tobacco leads to enhanced resistance to Phytophthora parasitica pv. nicotianae and Cercospora nicotianae. AB - Abstract Previous research indicated that the constitutive expression of a pathogen-inducible peroxidase gene (Shpx6a) from Stylosanthes humilis in transgenic plants resulted in enhanced resistance to fungal pathogens ( Kazan, K., Goulter, K.C., Way, H.M. and Manners, J.M. (1998) Expression of a pathogenesis-related peroxidase of Stylosanthes humilis in transgenic tobacco and canola and its effect on disease development. Plant Sci. 136, 207-217). We have now investigated another pathogen-inducible peroxidase gene of S. humilis, termed Shpx2, which is highly divergent from Shpx6a. Constitutive expression of the Shpx2 cDNA was obtained in tobacco using the 35S CaMV promoter, and up to a 12 fold increase in total peroxidase activity was observed in the leaves of transgenic plants compared to nontransgenic controls. Disease development was evaluated after inoculations in T(1) and T(2) transgenic lines expressing Shpx2. Lesion expansion was significantly (P < 0.05) reduced by up to 25% and 50% on leaves and stems, respectively, of transgenic plants expressing high levels of peroxidase compared to nontransgenic controls, following inoculation with Phytophthora parasitica pv. nicotianae, the cause of black shank disease. In addition, plant survival and recovery were greatly enhanced in transgenic plants following stem inoculations of plants with this plant pathogen. A significant (55%, P < 0.05) reduction in lesion number was observed in transgenic plants with high levels of peroxidase activity following inoculation with the fungus Cercospora nicotianae, the cause of frog-eye disease. No significant differences in disease development were observed between the lines expressing Shpx2 and controls following inoculation with the bacterium Pseudomonas syringae pv. tabaci, the cause of wildfire disease. These results provide evidence for a role for this peroxidase gene in plant defence, and suggest that diverse peroxidase genes may be employed as components of strategies aimed at the engineering of disease resistance. PMID- 20572970 TI - Domain switching between hrpR and hrpS affects the regulatory function of the hybrid genes in Pseudomonas syringae pv. phaseolicola. AB - Abstract In prokaryotes, a diverse set of physiological processes is regulated by transcription factors which belong to the well-conserved, enhancer-binding protein (EBP) family. These regulatory proteins function together with the alternate sigma factor (sigma(54)). Structurally, the EBPs are characterized by a central activator domain, containing the recognition motif for the RNA polymerase/sigma(54) complex (Esigma(54)), and the C-terminal domain, containing a DNA-binding helix-turn-helix motif. A regulatory system of the EBP type also exists in Pseudomonas syringae, where it controls the expression of genes required for the induction of disease symptoms and resistance responses in plants. The system consists of the two genes, hrpR and hrpS, which belong to the hrp (hypersensitive response and pathogenicity) gene cluster. The two genes show a high degree of structural and sequence similarities, but function at different positions in the hrp regulatory cascade of the bean pathogen Pseudomonas syringae pv. phaseolicola. In this paper, we were interested in the basis of the difference in specificity between hrpR and hrpS. The functional specificities of the two domains of hrpS and hrpR were analysed by domain switching. Complementation analyses with the hybrid genes and retardation experiments with the protein products showed significant differences between the respective domains of hrpS and hrpR. PMID- 20572971 TI - A novel regulatory element involved in rapid activation of parsley ELI7 gene family members by fungal elicitor or pathogen infection. AB - Abstract In parsley (Petroselinum crispum), members of the ELI7 gene family were rapidly transcriptionally activated following treatment with an elicitor derived from the phytopathogen Phytophthora sojae. Several cDNA and genomic ELI7 clones were isolated. The deduced amino acid sequences revealed close similarity to fatty acid desaturases/hydroxylases, however, the precise functions are still unknown. Analysis of the promoters of two strongly elicitor-induced family members, ELI7.1 and ELI7.2, allowed us to functionally pinpoint a novel, independently acting regulatory region (S box), the only major sequence similarity between the two gene promoters. In situ RNA/RNA hybridization using an ELI7.1 gene-specific probe demonstrated that expression of this gene is rapidly and locally induced around infection sites in planta as well. PMID- 20572972 TI - Use of an isocitrate lyase promoter-GFP fusion to monitor carbon metabolism of the plant pathogen Tapesia yallundae during infection of wheat. AB - Abstract Green fluorescent protein (GFP) has been used as a vital marker in a variety of species. Here, we present the use of a GFP-promoter fusion to visualize carbon metabolism in a pathogenic fungus during growth on defined medium and during infection of plants. Isocitrate lyase (ICL), a key enzyme in carbon metabolism, is tightly regulated at the transcriptional level, with high levels of expression during 2-carbon growth and no expression during growth on glucose. A GFP-ICL promoter fusion was used to visualize carbon metabolism in the plant pathogenic fungus Tapesia yallundae during growth in vitro and in the host plant. The ICL promoter from Neurospora crassa retained its native induction and repression characteristics in T. yallundae. Loss of GFP fluorescence from hyphae after repression of the ICL promoter suggested a rapid turnover rate for GFP in T. yallundae. Regulation of this promoter was observed during infection, with expression occurring only on the plant surface, suggesting that 2-carbon metabolism occurs during this phase. These data suggest that GFP is a useful vital marker for the in planta imaging of fungal metabolism. PMID- 20572973 TI - Pseudomonas syringae pv. tomato: the right pathogen, of the right plant, at the right time. AB - Abstract Pseudomonas syringae pv. tomato and the closely related pathovar P. s. pv. maculicola have been the focus of intensive research in recent years, not only because of the diseases they cause on tomato and crucifers, but because strains such as P. s. pv. tomato DC3000 and P. s. pv. maculicola ES4326 are pathogens of the model plant Arabidopsis thaliana. Consequently, both P. s. pv. tomato and P. s. pv. maculicola have been widely used to study the molecular mechanisms of host responses to infection. Analyses of the molecular basis of pathogenesis in P. s. pv. tomato reveal a complex and intimate interaction between bacteria and plant cells that depends on the coordinated expression of multiple pathogenicity and virulence factors. These include toxins, extracellular proteins and polysaccharides, and the translocation of proteins into plant cells by the type III (Hrp) secretion system. The contribution of individual virulence factors to parasitism and disease development varies significantly between strains. Application of functional genomics and cell biology to both pathogen and host within the P. s. pv. tomato/A. thaliana pathosystem provides a unique opportunity to unravel the molecular interactions underlying plant pathogenesis. Taxonomic relationship: Bacteria; Proteobacteria; gamma subdivision; Pseudomonadaceae/Moraxellaceae group; Pseudomonadaceae family; Pseudomonas genus; Pseudomonas syringae species; tomato pathovar. Microbiological properties: Gram negative, aerobic, motile, rod-shaped, polar flagella, oxidase negative, arginine dihydrolase negative, DNA 58-60 mol% GC, elicits the hypersensitive response on tobacco. HOST RANGE: Primarily studied as the causal agent of bacterial speck of tomato and as a model pathogen of A. thaliana, although it has been isolated from a wide range of crop and weed species. Disease symptoms: Tomato (Lycopersicon esculentum): Brown-black leaf spots sometimes surrounded by chlorotic margin; dark superficial specks on green fruit; specks on ripe fruit may become sunken, and are surrounded by a zone of delayed ripening. Stunting and yield loss, particularly if young plants are infected. Reduced market value of speckled fruit. A. thaliana: Water-soaked, spreading lesions, sometimes surrounded by chlorotic margin. EPIDEMIOLOGY: Seed borne. Survives as a saprophyte in plant debris, soil and on leaf surfaces. Dispersed by aerosols and rain splash. Development of disease symptoms favoured by leaf wetness and cool temperatures (55-77 degrees F/13-25 degrees C). Disease control: Pathogen-free seed and transplants. Resistant and tolerant cultivars. Sanitation, rotation, and drip irrigation to reduce leaf wetness. Some measure of control with bactericides (copper, streptomycin). PMID- 20572974 TI - Expression analysis of genes induced in barley after chemical activation reveals distinct disease resistance pathways. AB - Abstract Salicylic acid (SA) and its synthetic mimics 2,6-dichloroisonicotinic acid (DCINA) and benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH), protect barley systemically against powdery mildew (Blumeria graminis f.sp. hordei, Bgh) infection by strengthening plant defence mechanisms that result in effective papillae and host cell death. Here, we describe the differential expression of a number of newly identified barley chemically induced (BCI) genes encoding a lipoxygenase (BCI-1), a thionin (BCI-2), an acid phosphatase (BCI-3), a Ca(2+)-binding EF-hand protein (BCI-4), a serine proteinase inhibitor (BCI-7), a fatty acid desaturase (BCI-8) and several further proteins with as yet unknown function. Compared with SA, the chemicals DCINA and BTH were more potent inducers of both gene expression and resistance. Homologues of four BCI genes were detected in wheat and were also differentially regulated upon chemical activation of disease resistance. Except for BCI-4 and BCI-5 (unknown function), the genes were also induced by exogenous application of jasmonates, whereas treatments that raise endogenous jasmonates as well as wounding were less effective. The fact that BCI genes were not expressed during incompatible barley-Bgh interactions governed by gene-for-gene relationships suggests the presence of separate pathways leading to powdery mildew resistance. PMID- 20572975 TI - Mutations in Ror1 and Ror2 genes cause modification of hydrogen peroxide accumulation in mlo-barley under attack from the powdery mildew fungus. AB - Abstract Race nonspecific resistance of barley against the barley powdery mildew fungus (Blumeria Graminis f.sp. Hordei, Speer, Bgh) is mediated by recessive mlo alleles and is controlled by at least two additional genes 'required for ml o specified disease resistance' (Ror1 and Ror2). The pathogenesis-related accumulation of hydrogen peroxide (H(2)O(2)) was comparatively analysed in a susceptible barley line (Hordeum vulgare L. Cv Ingrid, genotype Mlo Ror1, Ror2), a resistant Ingrid backcross line carrying the mutant allele mlo5 (BCIngrid-mlo5, genotype mlo5 Ror1 Ror2), and in the moderately susceptible mutants A44 and A89 (genotypes mlo5 Ror1 ror2 and mlo5 ror1-2 Ror2, respectively). In situ localization of H(2)O(2) was performed by microscopic detection of 3,3 diaminobenzidine (DAB) polymerization. In BCIngrid-mlo5, penetration resistance against Bgh attack was closely correlated to H(2)O(2) accumulation in cytoplasmic aggregates and cell wall appositions beneath the appressorium. In contrast, H(2)O(2) accumulation was almost completely absent in susceptible Ingrid. Lines with mutations in Ror genes showed less H(2)O(2) accumulation beneath appressoria, but more interaction sites with whole cell H(2)O(2) accumulation and hypersensitive cell death response than resistant BCIngrid-mlo5. Thus, mutations in Ror1 or Ror2 genes influence the cellular pattern of H(2)O(2) accumulation in mlo plants attacked by Bgh. The data support the hypothesis that H(2)O(2) accumulation is involved in resistance to fungal penetration. PMID- 20572976 TI - Genome analysis of the plant pathogenic ascomycete Leptosphaeria maculans; mapping mating type and host specificity loci. AB - Abstract A genetic and physical map has been developed for the loculoascomycete Leptosphaeria maculans, a pathogen of oilseed Brassicas. The genetic map was constructed from 58 F(1) progeny and comprises 155 amplified fragment length polymorphic (AFLP) markers, three random amplified polymorphic DNA (RAPD) markers, the mating type locus and a host specificity locus conferring the ability to form lesions on Brassica juncea. Twenty-one linkage groups, 5 pairs, and 18 unlinked markers were assigned, and the genome size was 1520 cM. Pulsed field gel electrophoresis experiments showed that the parental isolates each had 16 chromosomes and a genome size of about 33.5 Mb. Attempts to anchor a large number of markers to chromosomes were hampered by difficulties in converting AFLPs into RFLP markers, and because many markers bound to every chromosome, indicating that L. maculans has a high level of dispersed repetitive sequences. This fungus displays chromosomal length polymorphisms, but in the cross examined, the linkage and physical maps were essentially congruent and there was no evidence of translocations. The host specificity locus is 18 cM from the nearest AFLP marker and is located on a chromosome sized 1.85 Mb in the virulent parent. The mating type locus is on a chromosome sized 2.6 Mb and coincident on an AFLP marker amplified from the virulent parent. The derived amino acid sequence of part of this marker has some conserved amino acids present in the High Mobility Group DNA binding domain of MAT-2 mating type genes of other ascomycetes. PMID- 20572977 TI - Up-regulation of the ascorbate-dependent antioxidative system in barley leaves during powdery mildew infection. AB - Abstract The ascorbate-dependent antioxidative system was studied in leaves of barley infected with the barley powdery mildew fungus Blumeria graminis f.sp. hordei (Bgh). Increased ascorbate peroxidase (APX) activity was detected upon infection, especially in the compatible interaction. APX activity was determined in epidermal and total leaf tissues. A relatively higher increase in APX activity was found in the epidermis compared to total leaf 72 h after inoculation in the compatible interaction, but the increase was not restricted to the epidermis. Activity assays in native gels and Northern blot hybridization indicated that the increase in APX activity was caused by a cytosolic APX isoform. 'Inverse Northern blot' hybridization results with the cDNA of a cytosolic APX supported the relatively higher increase in epidermal APX activity compared to total leaf activity. In the compatible interaction, monodehydroascorbate reductase (MDHAR) activity increased in temporal and spatial patterns similar to that of APX activity. In contrast to this, dehydroascorbate reductase and glutathione reductase activities either decreased or were unaffected by Bgh infection. The increase in APX and MDHAR activities in the compatible interaction continued until severe infection of the leaves. Thus, an up-regulation of the antioxidative system of the host cells could play a role for maintenance of the biotrophic relationship between Bgh and the barley leaf by preventing proliferating oxidative processes, which would otherwise be harmful to the living plant cell on which the biotrophic powdery mildew fungus depends. PMID- 20572978 TI - Methionine synthase, a gene required for methionine synthesis, is expressed in planta by Cladosporium fulvum. AB - Abstract The nutritional requirements of phytopathogenic fungi growing in planta has to date been largely ignored. We have begun to address this problem by investigating the methionine requirement for the biotrophic pathogen of tomato Cladosporium fulvum during infection. The Met6 gene from Cladosporium fulvum encoding a cobalamin-independent 5-methyltetrahydropteroyltriglutamate homocysteinemethyltransferase, was cloned by functional yeast complementation. The open reading frame was found to be 2304 bp, containing no introns and encoding a protein of 87 kDa. In vitro Northern analysis demonstrated high levels of Met6 expression in the absence of externally supplied methionine. However in the presence of methionine or in the absence of carbon, expression of Met6 decreased significantly. Analysis of Met6 expression in planta revealed a strong increase during infection suggesting the requirement for methionine synthesis in planta by Cladosporium fulvum. This study demonstrates that Cladosporium fulvum is starving for methionine during infection and thus implies the essentiality of primary biosynthetic pathways to the infecting fungus. PMID- 20572979 TI - Erwinia amylovora: the molecular basis of fireblight disease. AB - Summary Taxonomy: Bacteria; Proteobacteria; gamma subdivision; order Enterobacteriales; family Enterobacteriaceae; genus Erwinia. Microbiological properties: Gram-negative, motile rods. Related species:E. carotovora (soft-rot diseases), E. chrysanthemi (soft-rot diseases), E. (Pantoea) stewartii (Stewart's wilt of corn), E. (Pantoea) herbicola (epiphyte). HOST RANGE: Affects rosaceous plants, primarily members of the Pomoideae. Economically important hosts are apple and pear. The commercial implications of fireblight outbreaks are aggravated by the limited effectiveness of current control measures. Disease symptoms:E. amylovora infection is characterized by water soaking of infected tissue, followed by wilting and tissue necrosis. Necrosis gives tissue a scorched, blackened appearance, giving rise to the name fireblight. Symptoms are often localized to blossom bracts or young shoots but, in highly susceptible hosts, can spread systemically resulting in death of the entire tree. Infections can vary in severity depending on climatic conditions and host susceptibility. Useful web site:http://www.agric.gov.ab.ca. PMID- 20572980 TI - Strawberry crinkle virus, a Cytorhabdovirus needing more attention from virologists. AB - Summary Taxonomic relationship: A member of nonsegmented, negative-sense, single stranded RNA viruses of the genus Cytorhabdovirus (type member: Lettuce necrotic yellows virus), family Rhabdoviridae, order Mononegavirales. Members of the family Rhabdoviridae can infect vertebrates, invertebrates and plants. Physical properties: Virions are bacilliform, 74-88 nm in diameter and 163-383 nm in length with surface projections probably composed of trimers of the glycoprotein G, occurring in the cytoplasm in either the coated or the uncoated form (Fig. 1). The nucleocapsid is enclosed in a host-derived envelope. Within the virion, the SCV genome consists of a single negative-sense single-stranded RNA molecule of approximately 13 kb. Viral proteins: The SCV genome encodes at least five proteins: the nucleocapsid (N) protein (45 kDa), the matrix (M) protein (77 kDa), the nonstructural protein [Ns, 55 kDa, also known as phosphoprotein (P)], the glycoprotein (G, 23 kDa) and the large (L) protein. Hosts: The natural host range of SCV is limited to species of the genus Fragaria L. Experimental hosts include Physalis pubescens L., P. floridana Rydb., Nicotiana occidentalis, N. glutinosa L. and N. clevelandi Gray. SCV also replicates in its insect vectors Chaetosiphon fragaefolii Cockerell and C. jacobi Hille Ris Lamberts. When injected as purified virus, SCV replicates in aphids Hyperomyzus lactucae (L.), Macrosiphon euphorbiae Thomas, Myzus ornatus Laing, Megoura viciae Buckton, and Acyrthosiphoa pisum (Harris). PMID- 20572981 TI - Genomic plus-strand RNA synthesis by the brome mosaic virus (BMV) RNA replicase requires a sequence that is complementary to the binding site of the BMV helicase like protein. AB - Summary Initiation of genomic plus-strand RNA synthesis by the brome mosaic virus (BMV) replicase in vitro requires a 26-nucleotide (nt) RNA sequence at the 3' end of the minus-strand RNA and a nontemplated nucleotide 3' of the initiation cytidylate [Sivakumaran, K. and Kao, C.C. (1999)J. Virol.64, 6415-6423]. At the 5' end of this RNA is a 9-nt sequence called the cB box, the complement of the previously defined B box. The cB box can not be functionally replaced by the B box and has specific positional and sequence requirements. The portion of the cB box that is required for RNA synthesis in vitro is well-conserved in species in the Bromoviridae family. An equivalent RNA from Cucumber mosaic virus was unable to direct efficient RNA synthesis by the BMV replicase until the cB box was positioned at the same site relative to the BMV RNA and guanylates were present at positions +6 and +7 from the initiation cytidylate. These results further define the elements required for the recognition and initiation of viral genomic plus-strand RNA synthesis and suggest that a sequence important for minus-strand RNA synthesis is also required for plus-strand RNA synthesis. PMID- 20572982 TI - A single copy of a virus-derived transgene encoding hairpin RNA gives immunity to barley yellow dwarf virus. AB - Summary Barley yellow dwarf virus-PAV (BYDV-PAV) is the most serious and widespread virus of cereals worldwide. Natural resistance genes against this luteovirus give inadequate control, and previous attempts to introduce synthetic resistance into cereals have produced variable results. In an attempt to generate barley with protection against BYDV-PAV, plants were transformed with a transgene designed to produce hairpin (hp)RNA containing BYDV-PAV sequences. From 25 independent barley lines transformed with the BYDV-PAV hpRNA construct, nine lines showed extreme resistance to the virus and the majority of these contained a single transgene. In the progeny of two independent transgenic lines, inheritance of a single transgene consistently correlated with protection against BYDV-PAV. This protection was rated as immunity because the virus could not be detected in the challenged plants by ELISA nor recovered by aphid feeding experiments. In the field, BYDV-PAV is sometimes associated with the related luteovirus Cereal yellow dwarf virus-RPV (CYDV-RPV). When the transgenic plants were challenged with BYDV-PAV and CYDV-RPV together, the plants were susceptible to CYDV-RPV but immune to BYDV-PAV. This shows that the immunity is virus specific and not broken down by the presence of CYDV. It suggests that CYDV-RPV does not encode a silencing-suppressor gene or that its product does not protect BYDV-PAV against the plant's RNAi-like defence mechanism. Either way, our results indicate that the BYDV-PAV immunity will be robust in the field and is potentially useful in minimizing losses in cereal production worldwide. PMID- 20572983 TI - A thaumatin-like gene from Asparagus officinalis (AoPRT-L) exhibits slow activation following tissue maceration or salicylic acid treatment, suggesting convergent defence-related signalling in monocots. AB - Summary Messenger RNA derived from mechanically separated cells of asparagus has proved to be an enriched source of defence-related transcripts. We describe the characterization of a novel PR-5 gene coding for a secreted protein of neutral pI (AoPRT-L) that is strongly up-regulated following cell isolation or following accelerated tissue ageing caused by tissue maceration, but which is also responsive to salicylic acid, a defence-related signal not normally associated with wound responses. Infection with the necrotizing fungal pathogen Stemphylium vesicarium confirmed the responsiveness of AoPRT-L to pathogen challenge in intact plants. An upstream region of the AoPRT-L gene of less than 500 bp was sufficient to confer SA-inducibility in transgenic tobacco. The expression profile of AoPRT-L in both macerated and pathogen challenged tissue suggested there were complex, convergent signalling mechanisms operating during responses to these different stresses. PMID- 20572984 TI - A PR-5 gene promoter from Asparagus officinalis (AoPRT-L) is not induced by abiotic stress, but is activated around sites of pathogen challenge and by salicylate in transgenic tobacco. AB - Summary Using a promoter-uidA (AoPRT-L-GUS) construct, we have characterized heterologous expression controlled by an Asparagus officinalis acidic PR-5 gene promoter. The construct was found to be up-regulated following a variety of treatments with the defence signal salicylate. Similarly, AoPRT-L-GUS was induced by the SA mimic benzothiodiazole, however, unlike salicylate, this compound does not appear to be transported through the vasculature. The construct was insensitive to wounding and to the wound signal jasmonate. Pathogen challenge resulted in a restricted zone of expression at and around the infection site. High levels of NaCl or PEG 8000 failed to induce foliar expression, however, mannitol proved to be an effective inducer when applied as a root drench. The oxidants H(2)O(2) and t-butyl hydroperoxide also failed to induce AoPRT-L-GUS expression. Developmental expression of the construct appeared to be limited to leaf axils, sepal tips, a proportion of anthers and a small segment of tissue just below the stigma. Thus, the AoPRT-L promoter exhibits a limited expression profile responding principally to salicylate-related defence signals, and shows very little developmental expression. This suggests that the AoPRT-L promoter may be an ideal choice for contained gene expression. PMID- 20572985 TI - Two natural cerato-ulmin (CU)-deficient mutants of Ophiostoma novo-ulmi: one has an introgressed O. ulmi cu gene, the other has an O. novo-ulmi cu gene with a mutation in an intron splice consensus sequence. AB - Summary The nucleotide sequences of the cerato-ulmin (cu) genes of two naturally occurring pathogenic CU-deficient mutants, PG470 and MAFf8, of the Dutch elm disease fungus, Ophiostoma novo-ulmi, were determined. The PG470 cu gene sequence was identical to that of CU-secreting isolates of O. novo-ulmi, except for a G to A mutation in the GT splice consensus sequence at the start of intron 1, suggesting that the CU deficiency was due to a splicing defect in the premRNA. In contrast, the MAFf8 cu gene showed a 99.1% sequence identity with cu genes of O. ulmi isolates, but only 92.8% sequence identity with cu genes of CU-secreting isolates of O. novo-ulmi, and in a dendrogram clustered with cu gene sequences of O. ulmi isolates with 100% bootstrap support. Restriction fragment length polymorphisms of the ribosomal RNA region, random amplified polymorphic DNA markers, and many biological properties of MAFf8, including pathogenicity, were typical of O. novo-ulmi. It is therefore likely that the cu gene of MAFf8 has been introgressed from O. ulmi, probably as a result of rare hybrid formation between O. ulmi and O. novo-ulmi, followed by backcrossing of the hybrid with O. novo-ulmi. The presence of an O. ulmi-like cu gene in MAFf8 is consistent with its CU deficiency, since the O. ulmicu gene is known to be poorly expressed and O. ulmi isolates secrete little or no CU in culture. PMID- 20572986 TI - Nematodes as vectors to introduce Agrobacterium into plant roots. AB - Summary A fast plant promoter test was developed by means of a nematode to transfer Agrobacterium tumefaciens into plant roots. Two-week-old Arabidopsis thaliana (L.) Heynh. plants were transferred to infection medium. Meloidogyne incognita or Heterodera schachtii juveniles were mixed with the Agrobacterium strain that harboured the binary vector, and this mixture was used for plant inoculation. During migration of the nematode and establishment of the feeding site inside the roots, the T-DNA was delivered into the root cells. A few days later, the infected plants could be analysed for expression of the T-DNA reporter gene in and around the nematode feeding sites (NFS), without the need to go first through the whole transformation and regeneration procedure. Depending on the construct, expression of the beta-glucuronidase gene in the NFS or along the migration path of the nematode could be seen in the roots of Arabidopsis plants. Furthermore, stably transformed plants could be regenerated from the infected roots. PMID- 20572987 TI - Xanthomonas albilineans and the antipathogenesis approach to disease control. AB - Summary Molecular studies into sugarcane leaf scald disease, caused by X. albilineans, revealed an unusual pathogenesis strategy, a new family of antibiotics, an extraordinary biosynthetic apparatus, and a new approach to disease control in plants and animals. TAXONOMY: Bacteria; Proteobacteria; gamma subdivision; Xanthomonadales; Xanthomonas group; X. albilineans (Ashby 1929) Dowson 1943. Microbiological properties: Gram-negative, slender rod-shaped, nonsporing, aerobic, motile by a single polar flagellum; producing slow-growing, pale yellow, nonmucoid colonies in culture; ecologically obligate plant parasite. HOST RANGE: Monocotyledonous plants in the Poaceae family, including Saccharum spp. and other grasses. Causal agent of sugarcane leaf scald. Disease symptoms: Characteristic white leaf stripes with necrotic zones at leaf margins, extensive chlorosis of emerging leaves, vascular reddening and cavity formation in invaded stems, production of side shoots, rapid wilting and death of plants. Prolonged latent infection can occur, necessitating detection by isolation or sensitive molecular assays. PATHOGENESIS: Xylem-invading pathogen, transmitted in cuttings, mechanically, and by wind-blown rain. Produces albicidin toxins that block prokaryotic DNA replication and plastid development, causing chlorosis in emerging leaves. Albicidins interfere with host resistance mechanisms, allowing systemic invasion. Strains vary in virulence. Agronomic importance and control: Sugarcane leaf scald is a widespread and devastating disease. Eradication is impractical because of alternative hosts. Measures to reduce inoculum sources and transmission can reduce losses. Long-term control requires sugarcane varieties with introgressed resistance, thus limiting gains from breeding. Antipathogenesis approach: By understanding key pathogenicity factors (such as albicidins), it may be possible to develop new control strategies, including novel resistance genes to rescue susceptible varieties. Useful web site:http://cygnus.tamu.edu/Texlab/Sugarcrops/Sugarcane/sugarc.html. PMID- 20572988 TI - Spontaneous deletion enhances movement of a cucumber necrosis virus based chimera expressing the red clover necrotic mosaic virus movement protein genedagger. AB - Summary The 35-kDa movement protein (MP) gene of red clover necrotic mosaic virus (RCNMV) and 3' flanking sequence were inserted in a cucumber necrosis virus (CNV) deletion mutant lacking a large portion of the coding region for the MP. Nicotiana benthamiana plants inoculated with chimeric synthetic transcripts of the resulting hybrid cDNA clone (M5/RM2) developed both local and systemic symptoms and accumulated high levels of chimeric viral RNA. Reverse transcriptase polymerase chain reaction (RT-PCR) and sequence analysis of viral RNA extracted from systemically infected leaves of four different plants revealed that in each plant a large portion (305, 308, 315 or 127 nts) of the 3' terminus of the inserted sequence spontaneously deleted during infection. In three of the deletion derivatives, the truncated RCNMV MP open reading frame (ORF) was fused in-frame with the remaining portion of the 3' terminal region of CNV MP ORF. The movement efficiencies of M5/RM2, a cloned copy of one of the deletion derivatives (ClM5/RM2dd1), and a stop codon mutant of ClM5/RM2dd1 (ClM5/RM2dd1stop), which prevents translational fusion to the CNV MP, were compared and it was determined that deletion of RCNMV MP sequences in conjunction with fusion to CNV MP sequences increases the movement efficiency of the chimeric virus genome. Absence of the C-terminal region of the RCNMV MP in RCNMV RNA-2 abolished RCNMV movement. However, movement could be complemented in trans if cells were coinoculated with ClM5/RM2dd1. Complementation of RCNMV movement did not occur using ClM5/RM2dd1stop, suggesting a role for appended CNV MP sequences in movement of the RCNMV genome. The ability of the CNV replicase to delete unnecessary or deleterious RCNMV sequences and to append the required CNV MP sequences reinforces the role of RNA recombination in the adaptation and evolution of viral genomes. PMID- 20572989 TI - Transgenic citrus plants expressing the citrus tristeza virus p23 protein exhibit viral-like symptoms. AB - Summary The 23 kDa protein (p23) coded by the 3'-terminal gene of Citrus tristeza virus (CTV), a member of the genus Closterovirus with the largest genome among plant RNA viruses, is an RNA-binding protein that contains a motif rich in cysteine and histidine residues in the core of a putative zinc-finger domain. On this basis, a regulatory role for CTV replication or gene expression has been suggested for p23. To explore whether over-expression of this protein in transgenic plants could affect the normal CTV infection process, transgenic Mexican lime plants were generated carrying the p23 transgene, or a truncated version thereof, under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Constitutive expression of p23 induced phenotypic aberrations that resembled symptoms incited by CTV in non-transgenic lime plants, whereas transgenic plants expressing the p23 truncated version were normal. The onset of CTV-like symptoms in p23-transgenic plants was associated with the expression of p23, and its accumulation level paralleled the intensity of the symptoms. This demonstrates that p23 is involved in symptom development and that it most likely plays a key role in CTV pathogenesis. This is the first case in which a protein encoded by a woody plant-infecting RNA virus has been identified as being directly involved in pathogenesis in its natural host. This finding also delimits a small region of the large CTV genome for the future mapping of specific pathogenic determinants. PMID- 20572990 TI - Mutational analysis of Turnip crinkle virus movement protein p8. AB - Summary Turnip crinkle virus encodes two proteins, p8 and p9, that are both required for cell-to-cell movement. The p8 movement protein has been demonstrated to bind RNA in a cooperative manner, although, similar to many other plant virus movement proteins, it contains no canonical RNA binding domain(s). However, three positively charged regions of p8 may potentially form ionic interactions with the RNA backbone. To identify functional regions of p8, a series of alanine and deletion scanning mutations were produced. The effects of these mutations were analysed using both in vitro RNA binding assays and in vivo infections of susceptible (Di-3) and resistant (Di-17) Arabidopsis thaliana plants. Several mutants that have reduced RNA binding ability were also demonstrated to be movement deficient and replication competent. Based on these results, there appear to be two regions, located between amino acids 18 and 31, and 50 and 72, that are required for RNA binding. Furthermore, additional regions (amino acids 12-15, and 34-37) appear to play a role in vivo unrelated to in vitro RNA binding activity. PMID- 20572991 TI - The application of real-time PCR to the identification, detection and quantification of Pyrenophora species in barley seed. AB - Summary A real-time quantitative PCR technique has been used to develop a rapid and sensitive seed health test for Pyrenophora spp. on barley seed. Using the fluorescent reporter dye SYBR Green I for real-time detection of PCR amplification, pathogen DNA extracted from infected seed can be quantified to the picogram level. The amount of Pyrenophora DNA extracted from seed samples of an artificial infection level gradient, constructed by mixing infected and uninfected seed, correlated with good agreement (r = 0.931) to percentage infection levels of the same samples measured by agar plate testing. In addition, a correlation of r = 0.883 was obtained between the two testing methods for naturally infected seed, ranging from 0% to 89% infection. Samples could be quantified to below the 2% voluntary threshold required for deciding on seed treatment. The proposed test was performed in three parts: (i) quantification of Pyrenophora spp. infection using Pyrenophora-specific PCR primers; (ii) test of any negative samples from (i) with barley-specific PCR primers to check the DNA extraction process; (iii) test of positive samples from (i) for the presence of Pyrenophora graminea using P. graminea-specific PCR primers. All PCRs were performed in the LightCycler instrument allowing each PCR run and analysis to be completed within 30 min. With the current daily receipt of samples (batches up to 16) the test can be completed in 8 h, compared to 7 days for the traditional agar plate test. PMID- 20572992 TI - Cucumber mosaic virus, a model for RNA virus evolution. AB - Summary Taxonomic relationships: Cucumber mosaic virus (CMV) is the type member of the Cucumovirus genus, in the family Bromoviridae. Additional members of the genus are Peanut stunt virus (PSV) and Tomato aspermy virus (TAV). The RNAs 3 of all members of the genus can be exchanged and still yield a viable virus, while the RNAs 1 and 2 can only be exchanged within a species. Physical properties: The virus particles are about 29 nm in diameter, and are composed of 180 subunits (T = 3 icosahedral symmetry). The particles sediment with an s value of approximately 98. The virions contain 18% RNA, and are highly labile, relying on RNA-protein interactions for their integrity. The three genomic RNAs, designated RNA 1 (3.3 kb in length), RNA 2 (3.0 kb) and RNA 3 (2.2 kb) are packaged in individual particles; a subgenomic RNA, RNA 4 (1.0 kb), is packaged with the genomic RNA 3, making all the particles roughly equivalent in composition. In some strains an additional subgenomic RNA, RNA 4A is also encapsidated at low levels. The genomic RNAs are single stranded, plus sense RNAs with 5' cap structures, and 3' conserved regions that can be folded into tRNA-like structures. Satellite RNAs: CMV can harbour molecular parasites known as satellite RNAs (satRNAs) that can dramatically alter the symptom phenotype induced by the virus. The CMV satRNAs do not encode any proteins but rely on the RNA for their biological activity. Hosts: CMV infects over 1000 species of hosts, including members of 85 plant families, making it the broadest host range virus known. The virus is transmitted from host to host by aphid vectors, in a nonpersistent manner. Useful web sites: http://mmtsb.scripps.edu/viper/1f15.html (structure); http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/10040001.htm (general information). PMID- 20572993 TI - Requirements for cell-to-cell movement of Barley stripe mosaic virus in monocot and dicot hosts. AB - Summary The Barley stripe mosaic virus (BSMV) RNAss genome contains a series of overlapping open reading frames termed the triple gene block. The three most abundant proteins, betab, betac and betad, have been shown to have essential roles in infectivity, but their function in cell-to-cell movement has not previously been unambiguously defined, nor has the role of a minor translational read-through protein, betad' been characterized. We have now examined the direct involvement of each of these proteins in cell-to-cell movement in planta by engineering fusions of the green fluorescent protein (GFP) to a cysteine-rich regulatory protein designated gammab. Microscopic examination of inoculated and systemically infected barley and oat leaves revealed high levels of fluorescence that moved rapidly through the compact striate vascular tissue without infecting epidermal cells. In contrast, a radial pattern of fluorescence spread through a large number of epidermal and mesophyll cells before entry into the reticulate vascular tissue of the dicot hosts Nicotiania benthamiana and Chenopodium amaranticolor. Mutational analyses indicated that the betab, betac and betad proteins are each essential for cell-to-cell movement in local lesion and systemic hosts, whereas the betad' protein is dispensable. Collectively, these results demonstrate conclusively that the three major triple gene block-encoded proteins act in concert to mediate cell-to-cell movement of BSMV. PMID- 20572994 TI - Specific recognition of AVR4 and AVR9 results in distinct patterns of hypersensitive cell death in tomato, but similar patterns of defence-related gene expression. AB - Summary Hypersensitive cell death occurs in tomato seedlings that are derived from a cross between plants that express a resistance (Cf) gene against the pathogenic fungus Cladosporium fulvum and plants that contain the matching avirulence (Avr) gene originating from this fungus. The pattern of Cf-9/Avr9- and Cf-4/Avr4-induced necrosis in these F(1) seedlings was found to differ significantly. Macroscopic observation revealed that in F(1) tomato seedlings containing both Cf-9 and Avr9, numerous necrotic spots developed that were scattered over the entire cotyledon, while the midvein and primary veins remained unaffected. In seedlings containing both Cf-4 and Avr4, however, initially only one or a few necrotic spots developed on each cotyledon, in most cases in the midvein and occasionally in primary veins. Subsequently, these spots turned rapidly into lesions that enlarged along the midvein and primary veins, eventually causing the cotyledons to wilt and abscise. These observations were confirmed by detailed histological studies. Production of the AVR proteins in adult tomato plants carrying the matching Cf gene, employing potato virus X, resulted in similar patterns of necrosis. RNA gel blot analysis demonstrated that both Avr4 and Avr9, controlled by the CaMV 35S promoter, were highly expressed in seedlings already at one day post-emergence, indicating that the distinct necrotic patterns are not due to differences in Avr expression levels. We have analysed the expression of many genes involved in defence signalling pathways and the defence response itself, during the onset of the Cf/Avr-initiated hypersensitive response (HR). Although most of the genes were expressed stronger and faster in Cf-4/Avr4 seedlings than in Cf-9/Avr9 seedlings at the onset of HR, no significant qualitative differences in the expression of genes involved in downstream signalling were observed when Cf-4/Avr4- and Cf-9/Avr9-induced defence responses were compared. PMID- 20572995 TI - White rust (Albugo candida) resistance loci on three Arabidopsis chromosomes are closely linked to downy mildew (Peronospora parasitica) resistance loci. AB - Summary Two accessions of Arabidopsis thaliana (Ksk-1 and Ksk-2) were used to identify and map three loci (RAC1, RAC2 and RAC3) of genes that confer Resistance to Albugo candida (white rust). The phenotypes associated with these genes were classified as either FN (necrotic flecks on upper surface of cotyledons and no blisters) for RAC2 and RAC3, or FYN (flecks surrounded by yellowing and no blisters) for RAC1. Both phenotypes exhibited rapid death of host cells penetrated by the parasite (hypersensitive response), with callose deposition commonly encasing the haustorium. F(6) recombinant inbred lines were produced specifically for the purpose of mapping each RAC locus relative to molecular markers. Dominant resistance at the locus RAC1 in Ksk-1 was previously mapped to chromosome 1 between RFLP markers m253 and m254, and co-segregating with a downy mildew resistance specificity RPP9 in the accession Wei-0. We report here a fine scale map interval and co-segregating markers for this locus, which in turn enabled mapping of a previously unnoticed source of resistance in Ksk-1 designated RAC3 that exhibits an FN phenotype hyperstatic to the FYN phenotype of RAC1. RAC3 is closely linked to the RPP8/HRT on chromosome 5, a locus which contains specificities for resistance to downy mildew and turnip crinkle virus. Recombinant inbreds also enabled mapping of recessive resistance at RAC2 in Ksk-2 to the bottom arm of chromosome 3, in the 6 cM interval between two downy mildew resistance loci (RPP1 and RPP13). PMID- 20572996 TI - The current state of plant virus taxonomy. PMID- 20572997 TI - Infection structures of biotrophic and hemibiotrophic fungal plant pathogens. AB - Summary Biotrophic plant pathogenic fungi are one of the major causes of crop losses. The infection processes they exhibit are typified by infected host plant cells remaining alive for several days. This requires the development of specialized infection structures such as haustoria which are produced by obligate biotrophs, and intracellular hyphae which are produced by many hemibiotrophs. These infection hyphae are surrounded by the host plant plasma membrane, and in the case of haustoria the extrahaustorial membrane differs biochemically and structurally from the normal membrane. An interfacial matrix separates haustoria and intracellular hyphae from the invaginated membrane and this seems to be characteristic of biotrophic interactions. There is clear evidence for molecular differentiation of the haustorial plasma membrane in powdery mildews and rusts in comparison with the other fungal membranes. Relatively few pathogenicity genes related to biotrophy, and the switch from biotrophy to necrotrophy in hemibiotrophs, have been identified. PMID- 20572998 TI - Targeting the targets of Type III effector proteins secreted by phytopathogenic bacteria. PMID- 20572999 TI - Tobacco mosaic virus, not just a single component virus anymore. AB - Summary Taxonomy: Tobacco mosaic virus (TMV) is the type species of the Tobamovirus genus and a member of the alphavirus-like supergroup. Historically, many tobamoviruses are incorrectly called strains of TMV, although they can differ considerably in sequence similarities and host range from each other and from TMV. Physical properties: TMV virions are 300 x 18 nm rods with a central hollow cavity (Fig. 1) and are composed of 95% capsid protein (CP), and 5% RNA. Each CP subunit interacts with 3-nts in a helical arrangement around the RNA. Virions are stable for decades; infectivity in sap survives heating to 90 degrees C. Hosts: The natural host range of TMV is limited; however, a broad range of weed and crop species, mostly Solanaceae that includes tobacco, pepper and tomato can be infected experimentally [Holmes, F.O. (1946) A comparison of the experimental host ranges of tobacco etch and tobacco mosaic viruses. Phytopathology, 36, 643-657]. TMV distribution is worldwide. No biological vectors are known. Useful website: http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/71010001.htm. PMID- 20573000 TI - Identification of potato genes induced during colonization by Phytophthora infestans. AB - Summary Suppression Subtractive Hybridization (SSH) was applied in a search for genes induced during the compatible interaction between Phytophthora infestans and potato. Using potato leaves that had been treated with benzo(1,2,3)thiadiazole-7-carbothioic acid S-methylester (BTH) as the control tissue, a low redundancy library with a relatively low frequency of the classic plant Pathogenesis-Related (PR) genes was generated. 288 of the clones were screened for induced sequences using Inverse Northern analysis (hybridizing the arrayed clones with radiolabelled cDNA populations). Of the 75 clones that were detectable by this method, 43 appeared to be induced. Eleven of these clones were then analysed by total RNA blot analysis, and elevation of transcript levels during P. infestans infection was confirmed for 10 of them. Some of the cDNAs analysed by RNA blot analysis have homology to genes already known to be induced during infection, e.g. to beta-1,3-glucanase. Another group of cDNAs have homology to enzymes involved in detoxification: gamma-glutamylcysteine synthetase, cytochrome P450, glutathione S-transferase and an MRP-type ABC transporter. Other infection induced cDNAs encode putative proteins that have not previously been reported to be induced by infection: e.g. the ER-located chaperone BiP, and a homologue of Aspergillus nidulans SudD, which was isolated as a suppressor of a mutation in chromosome disjunction. The differential library therefore presents the opportunity to analyse the metabolic changes occurring during infection, and the disease process itself in more detail. PMID- 20573001 TI - Reduced symptoms of Verticillium wilt in transgenic tomato expressing a bacterial ACC deaminase. AB - Summary Ethylene evolved during compatible or susceptible disease interactions may hasten and/or worsen disease symptom development; if so, the prevention of disease-response ethylene should reduce disease symptoms. We have examined the effects of reduced ethylene synthesis on Verticillium wilt (causal organism, Verticillium dahliae) of tomato by transforming tomato with ACC deaminase, which cleaves ACC, the immediate biosynthetic precursor of ethylene in plants. Three promoters were used to express ACC deaminase in the plant: (i) CaMV 35S (constitutive expression); (ii) rolD (limits expression specifically to the site of Verticillium infection, i.e. the roots); and (iii) prb-1b (limits expression to certain environmental cues, e.g. disease infection). Significant reductions in the symptoms of Verticillium wilt were obtained for rolD- and prb-1b-, but not for 35S-transformants. The pathogen was detected in stem sections of plants with reduced symptoms, suggesting that reduced ethylene synthesis results in increased disease tolerance. The effective control of formerly recalcitrant diseases such as Verticillium wilt may thus be obtained by preventing disease-related ethylene production via the tissue-specific expression of ACC deaminase. PMID- 20573002 TI - Characterization of a 20 kDa DNase elicitor from Fusarium solani f. sp. phaseoli and its expression at the onset of induced resistance in Pisum sativum. AB - Summary DNase released from Fusarium solani f. sp. phaseoli (Fsph DNase) has previously been reported to induce pathogenesis-related (PR) genes, phytoalexin accumulation and disease resistance against subsequent challenge with the true pea pathogen, Fusarium solani f. sp. pisi (Fspi). This report is a further analysis of DNase production with probes specific for both the gene and protein. N-terminal analysis of the approximately 20 kDa Fsph DNase protein facilitated both the development of anti-Fsph DNase antiserum and the cloning of the Fsph DNase gene. Utilizing the anti-Fsph DNase antiserum to prepare an affinity column, we demonstrated that the retention and recovery of the DNase activity was associated with this protein. Fsph DNase protein was detectable by Western analysis in both the fungi and plant cytoplasm within 6-8 h following inoculation of the pea endocarp surface. Partially purified DNase detected via catalytic activity began accumulating within pea tissue at 3 h post-inoculation. Enhanced fragmentation of pea DNA occurred within 5 h following treatment of pods with Fsph DNase or inoculations with the two fungi. DNA cleavage within the nuclei of endocarp pea cells was detectable via a TUNEL assay at 3 h post-inoculation. As a result of these findings, we propose that the entrance of Fsph DNase into the pea cell and the signalling of plant defence responses is temporally associated with the damage of host DNA. PMID- 20573003 TI - Isolation and characterization of novel defence-related genes induced by copper, salicylic acid, methyl jasmonate, abscisic acid and pathogen infection in Brassica carinata. AB - Summary To examine the defence response in Brassica carinata we differentially screened a cDNA library made from CuCl(2)-treated (Cu) leaves. The sequence of 17 of the 27 cDNA clones examined that showed Cu-induction had a high similarity to defence genes from other plant species. Among other clones that showed higher expression in the Cu leaves were two cDNAs encoding polypeptides of 351 and 250 amino acids, designated BcCJS1 and BcCJAS1. BcCJS1 had similarity to S-adenosyl-l methionine: salicylic acid carboxyl methyltransferase from Clarkia breweri. However, the enzyme activity was not found in extracts from E. coli expressing BcCJS1. BcCJAS1 did not show extensive similarity to any genes with known function in the databases but it did contain three regions of amino acid sequence that are frequently found in amidotransferases. A third Cu-induced mRNA, Bcp6PGL, showed very high (86%) similarity to a putative 6-phosphogluconolactonase (6PGL) from Arabidopsis thaliana. In addition to Cu induction, BcCJS1 expression was induced by methyl jasmonate (MeJA) and salicylic acid (SA), BcCJAS1 expression by MeJA, SA and abscisic acid and Bcp6PGL expression by MeJA. The expression of all three genes increased after Alternaria brassicae infection. BcCJS1 and BcCJAS1 were induced within 1 h after MeJA- but not until 3 h after SA-treatment. The expression of both genes was systemically induced after infection with a compatible or incompatible fungal pathogen. SA systemically induced only BcCJAS1. The effects of various inhibitors of signalling pathways on expression of the three genes were studied. PMID- 20573004 TI - Comparison between nuclear localization of nopaline- and octopine-specific Agrobacterium VirE2 proteins in plant, yeast and mammalian cells. AB - SUMMARY In a unique case of trans-kingdom DNA transfer, Agrobacterium genetically transforms plants by transferring its DNA segment into the host cell nucleus and integrating it into the plant genome. One of the central players in this process is the bacterial virulence protein, VirE2, which binds the transported DNA molecule and facilitates its nuclear import. Nuclear import of VirE2 proteins encoded by two major Agrobacterium strains, nopaline and octopine, has been hypothesized to occur by different mechanisms, i.e. the nopaline VirE2 was imported only into the nuclei of plant cells while the octopine VirE2 also accumulated in the nuclei of animal cells. Here, this notion was tested by a systematic comparison of nuclear import of nopaline- and octopine-specific VirE2 in dicotyledonous and monocotyledonous plants and in living mammalian and yeast cells. These experiments showed that nuclear import of both nopaline and octopine VirE2 proteins is plant-specific, occurring in plant but not in non-plant systems. PMID- 20573005 TI - DNA microarrays: new tools in the analysis of plant defence responses. AB - Summary Large-scale DNA sequencing is providing information on the number and organization of genes and genomes of plant species and their pathogens. The next phase is to identify gene functions and gene networks with key roles in compatible and incompatible plant-pathogen interactions. DNA microarrays can provide information on the expression patterns of thousands of genes in parallel. The application of this technology is already revealing new features of plant pathogen interactions and will be a key tool for a wide range of experiments in molecular plant pathology. PMID- 20573006 TI - Colletotrichum: tales of forcible entry, stealth, transient confinement and breakout. AB - Summary Taxonomy: Imperfect, anamorphic fungus (subdivision Deuteromycotina, form class Deuteromycetes, form-subclass Coelomycetidae, form-order Melanconiales, form-family Melanconiaceae) with 39 'accepted' species [Sutton, B.C. (1992) The genus Glomerella and its anamorph Colletotrichum. In: Colletotrichum: Biology, Pathology and Control (Bailey, J.A. and Leger, M.J., eds). Wallingford, UK: CAB International, pp. 1-26.] which continue to be revised and clarified by molecular taxonomic techniques. Species complexes and subspecific groups have been proposed. HOST RANGE: Species of Colletotrichum attack a large number of important tropical and sub-tropical crop species and cause economically significant diseases of cereals, grain legumes, vegetables, forage legumes, fruit crops and perennial crops. Tropical and sub-tropical fruit production is significantly affected by postharvest anthracnose. Disease symptoms: Symptoms of the attack are commonly known as anthracnose and comprise dark, sunken, lenticular necrotic lesions containing the acervuli of the pathogen. Key attractions: A model fungus for research on host specificity, mycoherbicides, appressorial melanization, appressorial function, quiescent infection, fungal lifestyles, intracellular hemibiotrophy and the determinants of the switch from biotrophy to necrotrophy among others. USEFUL WEBSITES: http://www.uark.edu/depts/plant/, http://www.sorghumanthracnose.org/, http://www.iacr.bbscr.ac.uk/ppi/staff/roc_rc.html. PMID- 20573007 TI - Non-host resistance of barley is associated with a hydrogen peroxide burst at sites of attempted penetration by wheat powdery mildew fungus. AB - Summary In barley, non-host resistance against the wheat powdery mildew fungus (Blumeria graminis f.sp. tritici, Bgt) is associated with the formation of cell wall appositions and a hypersensitive reaction in which epidermal cells die rapidly in response to fungal attack. In the interaction of barley with the pathogenic barley powdery mildew fungus (Blumeria graminis f.sp. hordei, Bgh), these defence reactions are also associated with accumulation of H(2)O(2). To elucidate the mechanism of non-host resistance, the accumulation of H(2)O(2) in response to Bgt was studied in situ by histochemical staining with diaminobenzidine. H(2)O(2) accumulation was found in cell wall appositions under appressoria from Bgt and in cells undergoing a hypersensitive reaction. A mutation (mlo5) at the barley Mlo locus, that confers broad spectrum resistance to Bgh, did not influence the barley defence phenotype to Bgt. Significantly, Bgt triggered cell death on mlo5-barley while Bgh did not. PMID- 20573008 TI - Analysis of the distribution and structure of integrated Banana streak virus DNA in a range of Musa cultivars. AB - Summary Banana streak virus strain OL (BSV-OL) commonly infects new Musa hybrids, and this infection is thought to arise de novo from integrated virus sequences present in the nuclear genome of the plant. Integrated DNA (Musa6+8 sequence) containing the whole genome of the virus has previously been cloned from cv. Obino l'Ewai (Musa AAB group), a parent of many of the hybrids. Using a Southern blot hybridization assay, we have examined the distribution and structure of integrated BSV-OL sequences in a range of Musa cultivars. For cv. Obino l'Ewai, almost every restriction fragment hybridizing to BSV-OL was predicted from the Musa6+8 sequence, suggesting that this is the predominant type of BSV-OL integrant in the genome. Furthermore, since only two junction fragments of Musa/BSV sequence were detected, and the Musa6+8 sequence is believed to be integrated as multiple copies in a tandem array, then the internal Musa spacer sequences must be highly conserved. Similarly sized restriction fragments were detected in four BB group cultivars, but not in six AA or AAA group cultivars, suggesting that the BSV-OL sequences are linked to the B-genome of Musa. We also provide evidence that cv. Williams (Musa AAA group) contains a distinct badnavirus integrant that is closely related to the 'dead' virus integrant previously characterized from Calcutta 4 (Musa acuminata ssp. burmannicoides). Our results suggest that the virus integrant from cv. Williams is linked to the A genome, and the complexity of the hybridization patterns suggest multiple sites of integration and/or variation in sequence and structure of the integrants. PMID- 20573009 TI - Gibberella fujikuroi mating population E is associated with maize and teosinte. AB - Summary Isolates of Fusarium subglutinans mating population E are usually found on maize. This fungus forms part of the so-called Gibberella fujikuroi species complex. Previously, F. subglutinans has been associated with two additional mating populations (B and H) and a variety of plant hosts. This was mainly due to a lack of diagnostic morphological characters, but the use of DNA sequence information showed that the strains making up mating populations B, E and H, as well as those associated with the different plant hosts, represent separate species. Recently, another putative mating population has been reported on the wild teosinte relatives of maize. Based on sexual compatibility studies, these isolates were apparently closely related to the pitch canker fungus, F. subglutinans f. sp. pini (= F. circinatum;G. fujikuroi mating population H). The aim of the current study was to determine whether the population of F. subglutinans from teosinte constitutes a new or an existing lineage within the G. fujikuroi complex. For this purpose, portions of the mitochondrial small subunit ribosomal DNA, calmodulin and beta-tubulin genes from the fungi were sequenced. Phylogenetic analyses and comparison with sequences from public domain databases indicated that the F. subglutinans isolates from teosinte are most closely related to strains of G. fujikuroi mating population E. These results were confirmed using sexual compatibility studies. The putative mating population from the wild relatives of maize therefore forms part of the existing E-mating population and does not constitute a new lineage in the G. fujikuroi species complex. PMID- 20573010 TI - A single amino acid change in the coat protein of Maize streak virus abolishes systemic infection, but not interaction with viral DNA or movement protein. AB - Summary Functional coat protein (CP) is important for host plant infection by monopartite geminiviruses. We identified a proline-cysteine-lysine (PCK) motif at amino acids 180-182 of the maize streak virus (MSV) CP that is conserved in most of the cereal-infecting Mastreviruses. Substitution of the lysine (K) with a valine (V) in the CP of MSV to produce mutant MSVCP182V abolished systemic infection in maize plants, although the mutant replicated around the inoculation site and, unlike other MSV CP mutants, enabled single-stranded (ss) DNA accumulation in suspension cells. The stability of the mutant protein, CP182V, in infected cells was confirmed by immunoblotting, but virions could not be detected. Like the wild-type (wt) CP, CP182V localized to the nucleus when expressed in insect and tobacco cells, and the Escherichia coli-expressed protein bound both ss and double-stranded DNA and interacted with movement protein in vitro. Taken together, these data suggest that mutation of amino acid 182 affects virion formation of MSV, either by affecting encapsidation per se or by affecting particle stability, and that virions are necessary for the long-distance movement of MSV in maize plants. PMID- 20573011 TI - Host-selective toxins as agents of cell death in plant-fungus interactions. AB - Summary Host-selective toxins are known determinants of compatibility in plant fungus interactions and provide a powerful model for understanding the specificity of these associations. The identification of genes required for toxin biosynthesis has shown that the genes are unique to the toxin producing species and are clustered in complex loci. These loci may have been acquired by horizontal gene transfer. Many, if not all, host-selective toxins act by disrupting biochemical processes and in several cases the resulting cell death has the characteristics of programmed cell death. This ability to make dead tissue from living has enabled these facultative saprophytic fungi to become plant pathogens. PMID- 20573012 TI - Pathogenicity genes of phytopathogenic fungi. AB - Summary Recently many fungal genes have been identified that, when disrupted, result in strains with a reduction or total loss of disease symptoms. Such pathogenicity genes are the subject of this review. The large number of pathogenicity genes identified is due to the application of tagged mutagenesis techniques (random or targeted). Genes have been identified with roles in the formation of infection structures, cell wall degradation, overcoming or avoiding plant defences, responding to the host environment, production of toxins, and in signal cascades. Additionally, genes with no database matches and with 'novel' functions have also been found. Improved technologies for mutation analysis and for sequencing and analysing fungal genomes hold promise for identifying many more pathogenicity genes. PMID- 20573013 TI - Phytophthora infestans enters the genomics era. AB - summary Phytophthora infestans, cause of late-blight, is the most devastating disease of potato world-wide. Recent years have seen a dramatic intensification in molecular biological studies of P. infestans, including the development of novel tools for transformation and gene silencing and the resources for genetical, transcriptional and physical mapping of the genome. This review will focus on the increasing efforts to use these resources to discover the genetic bases of pathogenicity, avirulence and host-specificity. TAXONOMY: Phytophthora infestans (Mont.) de Bary-Kingdom Chromista, Phylum Oomycota, Order Peronosporales, Family Peronosporaceae, Genus Phytophthora, of which it is the type species. HOST RANGE: Infects a wide range of solanaceous species. Economically important hosts are potato, tomato, eggplant and some other South American hosts (tree tomato and pear melon) on which it causes late blight. Disease symptoms: Infected foliage is initially yellow, becomes water soaked and eventually blackens. Leaf symptoms comprise purple-black or brown-black lesions at the leaf tip, later spreading across the leaf to the stem. Whitish masses of sporangia develop on the underside of the leaf. Tubers become infected later in the season and, in the early stages, consist of slightly brown or purple blotches on the skin. In damp soils the tuber decays rapidly before harvest. Tuber infection is quickly followed by secondary fungal or bacterial infection known as 'wet rot'. Useful web sites:http://www.ncgr.org/pgc/; http://www.oardc.ohio state.edu/phytophthora/. PMID- 20573014 TI - Comparison of endo-polygalacturonase activities of citrus and non-citrus races of Geotrichum candidum, and cloning and expression of the corresponding genes. AB - summary Geotrichum candidum citrus race, a fungus that causes a sour rot disease in citrus fruits, secretes an endo-polygalacturonase (PG) that may facilitate the disease. There also exists a non-citrus race that is non-pathogenic to citrus fruits. In this research, we found that the PG activity of the citrus race isolates was much higher than that of the non-citrus race isolates in culture medium and inoculated lemon peel, and that there was a significant correlation between the PG activity and pathogenicity. We isolated the two corresponding PG genes, S31pg1 and S63pg1, from citrus race S31 and non-citrus race S63, respectively. S31PG1 and S63PG1 consisted of 368 and 369 amino acids, respectively. The two PG genes showed 68% identity at the amino acid level. In expression studies, S31pg1 transcript was detected in mycelia grown in liquid cultures of citrus race S31 containing either glucose, pectin or lemon peel broth. The transcript was also detected in lemon peel inoculated with the isolate. On the other hand, no transcript of S63pg1 was detected in mycelia grown on any liquid cultures of non-citrus race S63 and lemon peel inoculated with the isolate. These results indicate that PG may play an important role in the development of the sour rot symptom and be involved in the difference of pathogenicity between the two races. PMID- 20573015 TI - Scorpion ARMS primers for SNP real-time PCR detection and quantification of Pyrenophora teres. AB - summary We have developed a quantitative PCR detection method that can be used to determine the seed infection levels of Pyrenophora teres, a seed-borne fungal pathogen of barley. This method uses Scorpion Amplified Refractory Mutation System (ARMS) technology with real-time PCR detection. Scorpion ARMS primers were designed and optimized such that a single nucleotide base mismatch in the primer sequence could distinguish P. teres from P. graminea, a closely related seed borne pathogen of barley. It is necessary to distinguish between these two agriculturally important pathogens since different disease management decisions are made, based on the presence and level of infection measured for each. The advance in development of sensitive and specific fluorescent probes has enabled the current PCR test to detect Pyrenophora spp. pathogenic on barley to be enhanced with the advantage that it can now specifically detect P. teres in a single reaction, whilst previously, two reactions were required to discriminate P. teres from P. graminea. PMID- 20573016 TI - The myrosinase-glucosinolate system in the interaction between Leptosphaeria maculans and Brassica napus. AB - summary Leptosphaeria maculans causes blackleg disease, and resistance to this fungal pathogen is an important trait in the breeding of oilseed rape. A better comprehension of the role of the myrosinase-glucosinolate system in this context is of great value. The present study is the first to address effects on multiple components of this complex system, including concentrations of individual glucosinolates, product formation, myrosinase isoform distribution and activity, and levels of myrosinase binding proteins during the infection process. One resistant B. napus cultivar (Maluka) and one susceptible cultivar (Westar) were compared in the investigation. Our results show that the two cultivars had the same histological distribution, isoform expression, and activity of the myrosinase enzymes. The glucosinolate levels were also similar, with the exception of glucobrassicin and neoglucobrassicin, which were significantly lower in the resistant cultivar at 11 days post-infection. Growth of the fungus on the plant tissues did not alter glucosinolate levels, suggesting that L. maculans does not degrade these compounds. When the plants were starved of sulphur, and thereby depleted of glucosinolates, no increased susceptibility was observed. Hence, we suggest that the myrosinase-glucosinolate system does not determine the outcome of the interaction between B. napus and L. maculans. PMID- 20573017 TI - Type III secretion and in planta recognition of the Xanthomonas avirulence proteins AvrBs1 and AvrBsT. AB - summary The hrp gene cluster of the plant pathogen Xanthomonas campestris pv. vesicatoria (Xcv) encodes a type III secretion system required for the delivery of virulence and avirulence proteins into the plant. Some of these effector proteins, e.g. AvrBs1 and AvrBsT, are recognized by pepper plants carrying corresponding resistance genes, triggering the hypersensitive reaction (HR). In this study, epitope tagged AvrBs1 and AvrBsT proteins were detected in culture supernatants only in the presence of a functional type III apparatus and not in a hrcV mutant, showing that both proteins are secreted by Xcv in an hrp-dependent manner. Expression of both avirulence genes is constitutive and independent of the hrp gene regulators, hrpG and hrpX. Transient expression of avrBs1 and avrBsT in resistant host plants using Agrobacterium tumefaciens-mediated gene transfer resulted in the induction of a specific HR. This indicates that recognition occurs intracellularly, and suggests that during the Xcv infection, AvrBs1 and AvrBsT are translocated from Xcv into the plant cell. We describe a conserved protein motif which is present in the N-terminal region of all known Xcv avirulence proteins and discuss its potential role in translocation into plant cells. PMID- 20573018 TI - Preparation and sequencing of secreted proteins from the pharyngeal glands of the plant parasitic nematode Heterodera schachtii. AB - summary In order to gain insight into the biology of the parasitic relationship between Heterodera schachtii and its host plant, it is important to understand the functional role of the nematode's pharyngeal secretions. These secretions presumably play a key role in establishing and maintaining a feeding site for the nematode. An optimized method was used for the in vitro production of H. schachtii pharyngeal gland secretions. These pharyngeal secretions were mainly produced in an insoluble form and could be solubilized under denaturing conditions for further analysis. The soluble fraction was concentrated with StrataClean (Stratagene, La Jolla, CA) or with a phenol/ether extraction. These methods made it possible for the first time to separate the secreted proteins on two-dimensional gels. By combining a micropreparative sample preparation with mass spectrometry, two beta-1,4-endoglucanases were identified. A third spot was identified as a novel protein by microsequencing. This is the first report on protein sequence information from pharyngeal secretions of a plant parasitic nematode. PMID- 20573019 TI - The tomato powdery mildew fungus Oidium neolycopersici. AB - summary Pathogen: Powdery mildew fungus; Ascomycete although sexual stage is yet to be found; an obligate biotroph. IDENTIFICATION: Superficial mycelium with hyaline hyphae; unbranched erect conidiophores; conidia, ellipsoid-ovoid or doliform, 22-46 x 10-20 microm, lack fibrosin bodies; conidia formed singly, rarely in short chains of 2-6 conidia; appressoria lobed to multilobed, rarely nipple-shaped. Pseudoidium species. HOST RANGE: Broad, reported to attack over 60 species in 13 plant families, particularly members of the Solanaceae and Curcubitaceae. SYMPTOMS: Powdery white lesions on all aerial plant parts except the fruit. In severe outbreaks the lesions coalesce and disease is debilitating. Agronomic importance: Extremely common in glasshouse tomatoes world wide but increasing in importance on field grown tomato crops. CONTROL: Chemical control and breeding programmes for disease resistance. PMID- 20573020 TI - Transient expression of a vacuolar peroxidase increases susceptibility of epidermal barley cells to powdery mildew. AB - summary The expression of genes encoding the peroxidases, Prx7 and Prx8, is induced in barley leaf tissue after inoculation with the barley powdery mildew fungus, Blumeria graminis f.sp. hordei (DC) Speer (Bgh). The role of these peroxidases in general barley defence responses against fungal attack was investigated using a transient expression system. Colonization frequencies of Bgh on cells transfected with Prx7 or Prx8 expression-, mutant- or fusion-DNA constructs were compared to the frequencies on cells expressing a beta glucuronidase (GUS) control construct. Twice the number of powdery mildew colonies were observed on cells expressing Prx7 as compared to control cells. Introduction of either mutant or truncated versions of Prx7 showed that decreased resistance against Bgh was dependent on the presence of the C-terminal signal peptide required for correct subcellular targeting, but not affected significantly by mutations in the catalytic centre. No impact on Bgh performance was observed after the introduction of Prx8 or mutant constructs. An enhanced accumulation of the apoplastic Prx8 was verified by immunocytology. These results indicate a more complex role of peroxidases in defence responses than was previously suspected. PMID- 20573021 TI - Microsatellite markers reflect intra-specific relationships between isolates of the vascular wilt pathogen Ceratocystis fimbriata. AB - summary Ceratocystis fimbriata is a serious wilt and canker stain pathogen with a wide geographical distribution and host range that includes both woody and herbaceous plants. Previous studies using hybridization have shown that isolates of C. fimbriata from different hosts and origins differ in colony morphology, pathogenicity and growth rate, as well as conidial state. It has therefore been suggested that distinct strains, linked to host or geographical origin, are encompassed in C. fimbriata. The aim of this study was to develop PCR-based microsatellite markers for population studies on C. fimbriata. ISSR-PCR was used to target specific microsatellite regions of DNA from C. fimbriata. These amplified products were cloned and sequenced. Primer pairs were designed from these sequences to flank the microsatellite regions. From 24 primer pairs, 11 polymorphic primers were selected and tested on a number of C. fimbriata isolates representing a wide host and geographical range. Cluster analyses of the results indicate that these markers clearly distinguish between different geographical and host specific populations of C. fimbriata. The results are concordant with sequence data from the internal transcribed spacer (ITS) region of the rDNA operon of the same isolates. These markers will be useful in future studies of C. fimbriata population structure and diversity. PMID- 20573022 TI - The barley powdery mildew protein kinase C gene, pkc1 and pkc-like gene, are differentially expressed during morphogenesis. AB - summary Protein kinase C agonist assays revealed the phorbol ester, phorbol 12 myristate 13-acetate, invoked germling morphogenesis and enhanced PKC activity in Blumeria graminis. No antagonist of mildew PKC activity was found but the data fuelled a hunt for powdery mildew pkc genes. Oligonucleotides, designed on the basis of conserved ATP-binding and kinase domains within the catalytic core of eukaryotic protein kinase proteins, were used as primers to amplify chromosomal and cDNA fragments from the barley powdery mildew fungus graminis. Three kinase gene fragments were isolated (pkc1, pkc-like and cpka) and the full length genomic sequences of the mildew pkc and pkc-like genes were determined by 'step down' PCR. RT-PCR transcript profiles showed the three genes to be differentially regulated during germling morphogenesis. PMID- 20573023 TI - Novel receptor-like protein kinases induced by Erwinia carotovora and short oligogalacturonides in potato. AB - summary Identification of potato genes responsive to cell wall-degrading enzymes of Erwinia carotovora resulted in the isolation of cDNA clones for four related receptor-like protein kinases. One of the putative serine-threonine protein kinases might have arisen through alternative splicing. These potato receptor like kinases (PRK1-4) were highly equivalent (91-99%), most likely constituting a family of related receptors. All PRKs and four other plant RLKs share in their extracellular domain a conserved bi-modular pattern of cysteine repeats distinct from that in previously characterized plant RLKs, suggesting that they represent a new class of receptors. The corresponding genes were rapidly induced by E. carotovora culture filtrate (CF), both in the leaves and tubers of potato. Furthermore, the genes were transiently induced by short oligogalacturonides. The structural identity of PRKs and their induction pattern suggested that they constitute part of the early response of potato to E. carotovora infection. PMID- 20573024 TI - Genes expressed during early stages of rice infection with the rice blast fungus Magnaporthe grisea. AB - summary A system-wide approach was adopted to further elucidate mechanisms regulating disease outcome between rice and the fungal pathogen Magnaporthe grisea. First, a cDNA library was constructed from M. grisea infected rice at 48 h post-inoculation. The 5' end-sequencing of 619 randomly selected clones revealed 359 expressed sequence tags (ESTs) that had not previously been described. A total of 124 from 260 ESTs with high and moderate similarity scores, based on BlastX, were organized into categories according to their putative function. The largest category of sequences (21%) contained stress or defence response genes. Eleven per cent of identified ESTs were redundant. In a second approach, differential hybridization analysis of the cDNA library using high density filters resulted in the identification of novel genes and previously characterized M. grisea genes, including several that had previously been implicated in the infection process. A survey of up-regulated cDNA clones revealed clone 29003, which corresponded to the rice peroxidase POX22.3. This gene is known to be expressed in rice upon infection with Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen. Importantly, this approach demonstrates the utility of gene discovery, through ESTs, for revealing novel genes in addition to those previously characterized as being potentially implicated in host-pathogen interactions. PMID- 20573025 TI - Avirulence proteins of plant pathogens: determinants of victory and defeat. AB - summary The simplest way to explain the biochemical basis of the gene-for-gene concept is by direct interaction between a pathogen-derived avirulence (Avr) gene product and a receptor protein, which is encoded by the matching resistance (R) gene of the host plant. The number of R genes for which the matching Avr gene has been cloned is increasing. The number of host-pathogen relationships, however, for which a direct interaction between R and Avr gene products could be proven is still very limited. This observation suggests that in various host-pathogen relationships no physical interaction between R and Avr proteins occurs, and that perception of AVR proteins by their matching R gene products is indirect. Indirect perception implies that at least a third component is required. The 'Guard hypothesis' proposes that this third component could be the virulence target of an AVR protein. Binding of the AVR protein to its virulence target is perceived by the matching R protein, which is 'guarding' the virulence target. An intriguing aspect of the 'Guard hypothesis' is that the Avr gene product causes avirulence of the pathogen through interaction with its virulence target in the plant. This would mean that, although AVR proteins are generally thought to be bifunctional (avirulence as well as virulence factors), this dual function might be based on a single biochemical event. This review focuses on the way AVR proteins are perceived by their matching R gene products. The various components that determine the outcome of the interaction will be discussed, with an emphasis on the dual function of AVR proteins. PMID- 20573026 TI - Corrigendum. PMID- 20573027 TI - Neuropathology of HTLV-1-associated myelopathy (HAM/TSP): The 50th Anniversary of Japanese Society of Neuropathology. AB - A series of our neuropathological studies was reviewed in order to clarify pathogenesis of human T lymphotropic virus type 1(HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The essential histopathologic finding was chronic inflammation in which inflammatory infiltrates of mononuclear cells and degeneration of myelin and axons were noted in the entire spinal cord. Immunohistochemical analysis demonstrated T-cell dominance, and the numbers of CD4+ cells and CD8+ cells were equally present in patients with shorter clinical courses. Apoptosis of helper/inducer T-cells were observed in these active inflammatory lesions. Horizontal distribution of inflammatory lesions was symmetric at all spinal levels and was accentuated at sites with slow blood flow in the middle to lower thoracic levels. HTLV-1 proviral DNA amounts were well correlated with the numbers of infiltrated CD4+ cells. In situ PCR of HTLV-1 proviral DNA and in situ hybridization of HTLV-1 Tax gene demonstrated the presence of HTLV-1-infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that T-cell mediated chronic inflammatory processes targeting the HTLV-1 infected T-cells is the primary pathogenic mechanism of HAM/TSP. Anatomically determined hemodynamic conditions may contribute to the localization of infected T-cells and the formation of main lesions in the middle to lower thoracic spinal cord. PMID- 20573028 TI - Early-stage progressive supranuclear palsy with degenerative lesions confined to the subthalamic nucleus and substantia nigra. AB - We describe a 78-year-old Japanese woman with early-stage progressive supranuclear palsy (PSP). She had a 3-week history of postural instability and gait disturbance. On examination, upper vertical gaze palsy, akinesia, hyperreflexia with pathological reflexes, hesitation, and postural instability were observed. Rigidity and resting tremors were not apparent. Brain MRI revealed atrophy of the frontotemporal lobes and dilatation of the third ventricle. A month later, she died of cerebral infarction. The total duration of her clinical course was approximately 2 months. The brain weighed 1180 g after fixation. Macroscopically, mild atrophy of the frontal lobes and mild depigmentation of the substantia nigra were observed. The conspicuous findings included degeneration confined to the subthalamic nucleus and substantia nigra and widespread but infrequent tau-positive neurofibrillary tangles/pretangles and glial fibrillary tangles (tuft-shaped astrocytes, coiled bodies and argyrophilic threads) in the brain. It has been reported that the most affected areas in PSP are the globus pallidus, subthalamic nucleus and substantia nigra. We suggest that degeneration in PSP would start with involvement of the substantia nigra and subthalamic nucleus. PMID- 20573029 TI - Pleomorphic pineocytoma associated with normal pineal parenchyma: report of a case in a 70-year-old man. AB - Pineocytomas (PCs) most frequently occur in adults, but only three cases have been reported in women older than 70 years. In PCs, cytologic pleomorphism, accompanied by ganglion cells intensely expressing neuronal markers, has been described and the presence of pleomorphic cells may lead to an erroneous upgrading of the tumor. We report an unusual case of pleomorphic pineocytoma in an older patient who presented with a slowly growing tumor adjacent to residual pineal gland. The immunohistological markers of the tumoral tissue and the remnant normal pineal tissue were evaluated and compared. In the neoplasm, the large number of cells labeled for neuronal markers, including many pleomorphic cells, confirmed previous findings that a neuronal immunophenotype is common in PC. Reactivity for synaptophysin was stronger in the tumor than the pineal gland, whereas neurofilament protein reactivity was stronger in the pineal gland than the tumor. The neoplastic cells, but not the pineal gland, were reactive for chromogranin A. This dense core vesicle-associated protein immunolabeling is an interesting diagnostic marker for PCs, which makes it possible to distinguish normal pineal parenchyma with low or negative expression from tumoral tissue. This case illustrates that, even though PCs are low-grade tumors, they can increase in size and surgery appears a valuable option. PMID- 20573030 TI - Pigmented pleomorphic xanthoastrocytoma: a rare variant and literature review. AB - A 16-year-old male teenager presented with seizure and loss of consciousness for 20 min. Magnetic resonance imaging demonstrated a mass occupying the right medial temporal lobe. Histological examination revealed a non-pigmented area with spindle-shaped and large xanthomatous pleomorphic cells and a pigmented region with pigmented neoplastic cells with fascicular arrangement. Immunohistochemical studies showed the tumor was positive for GFAP and low index of Ki-67. Considering the patient's history, clinical data and pathological findings, we rendered a rare variant named pigmented pleomorphic xanthoastrocytoma. PMID- 20573031 TI - Autoantibodies recognizing native MOG are closely associated with active demyelination but not with neuroinflammation in chronic EAE. AB - It is important to find biomarkers for autoimmune inflammation and demyelination in the CNS to monitor disease status in patients with multiple sclerosis (MS). For this purpose, we determined the titers of antibodies (Ab) reacting with native myelin oligodendrocyte glycoprotein (MOG)-expressing cells to evaluate the disease activity of chronic experimental autoimmune encephalomyelitis (EAE) in rats and the relationship between anti-MOGcme (cell membrane-expressed MOG), Ab titers and clinical and pathological parameters were evaluated. Consequently, we found that elevation of anti-MOGcme Ab titers was associated with clinical severity, except for some cases in very late stages and with severe and widespread demyelination but with dominant inflammation. In contrast, antibodies detected by standard ELISA using recombinant MOG were elevated in both symptomatic and asymptomatic rats and were not associated with parameters such as inflammation and demyelination. Longitudinal examination of anti-MOGcme Ab titers in individual rats revealed that Ab titers accurately reflect disease activity. Furthermore, anti-MOGcme Ab titer was not elevated in acute EAE without demyelination. These findings suggest that autoantibodies reacting with native and glycosylated MOG play an important role in the progression of demyelinating diseases and could be biomarkers for monitoring the status of patients with MS. PMID- 20573032 TI - Transplantation of human bone marrow stromal cell-derived Schwann cells reduces cystic cavity and promotes functional recovery after contusion injury of adult rat spinal cord. AB - The aim of this study was to evaluate whether transplantation of human bone marrow stromal cell-derived Schwann cells (hBMSC-SC) promotes functional recovery after contusive spinal cord injury of adult rats. Human bone marrow stromal cells (hBMSC) were cultured from bone marrow of adult human patients and induced into Schwann cells (hBMSC-SC) in vitro. Schwann cell phenotype was confirmed by immunocytochemistry. Growth factors secreted from hBMSC-SC were detected using cytokine antibody array. Immunosuppressed rats were laminectomized and their spinal cords were contused using NYU impactor (10 g, 25 mm). Nine days after injury, a mixture of Matrigel and hBMSC-SC (hBMSC-SC group) was injected into the lesioned site. Five weeks after transplantation, cresyl-violet staining revealed that the area of cystic cavity was smaller in the hBMSC-SC group than that in the control group. Immunohistochemistry revealed that the number of anti-growth associated protein-43-positive nerve fibers was significantly larger in the hBMSC SC group than that in the control group. At the same time, the number of tyrosine hydroxylase- or serotonin-positive fibers was significantly larger at the lesion epicenter and caudal level in the hBMSC-SC group than that in the control group. In electron microscopy, formation of peripheral-type myelin was recognized near the lesion epicenter in the hBMSC-SC group. Hind limb function recovered significantly in the hBMSC-SC group compared with the control group. In conclusion, the functions of hBMSC-SC are comparable to original Schwann cells in rat spinal cord injury models, and are thus potentially useful treatments for patients with spinal cord injury. PMID- 20573033 TI - An autopsied case of sporadic adult-onset amyotrophic lateral sclerosis with FUS positive basophilic inclusions. AB - Basophilic inclusions (BIs), which are characterized by their staining properties of being weakly argyrophilic, reactive with Nissl staining, and immunohistochemically negative for tau and transactive response (TAR) DNA-binding protein 43 (TDP-43), have been identified in patients with juvenile-onset amyotrophic lateral sclerosis (ALS) and adult-onset atypical ALS with ophthalmoplegia, autonomic dysfunction, cerebellar ataxia, or a frontal lobe syndrome. Mutations in the fused in sarcoma gene (FUS) have been reported in cases of familial and sporadic ALS, and FUS immunoreactivity has been demonstrated in basophilic inclusion body disease (BIBD), neuronal intermediate filament inclusion disease (NIFID), and atypical frontotemporal lobar degeneration with ubiquitin-positive and tau-negative inclusions (aFTLD-U). In the present study, we immunohistochemically and ultrastructurally studied an autopsy case of sporadic adult-onset ALS with numerous BIs. The patient presented with the classical clinical course of ALS since 75 years of age and died at age 79. Postmortem examination revealed that both Betz cells in the motor cortex and motor neurons in the spinal cord were affected. The substantia nigra was spared. Notably, BIs were frequently observed in the motor neurons of the anterior horns, the inferior olivary nuclei, and the basal nuclei of Meynert. BIs were immunopositive for p62, LC3, and FUS, but immunonegative for tau, TDP-43, and neurofilament. Ultrastructurally, BIs consisted of filamentous or granular structures associated with degenerated organelles with no limiting membrane. There were no Bunina bodies, skein-like inclusions, or Lewy-like inclusions. All exons and exon/intron boundaries of the FUS gene were sequenced but no mutations were identified. PMID- 20573034 TI - Association of allergic sensitization with infectious diseases burden in Roma and non-Roma children. AB - The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non Roma children who live in the same area. Analyses included 98 Roma and 118 non Roma children. Serum IgG antibodies for 13 foodborne- airborne- and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food- and aero-allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV-1, CMV, and Hepatitis B (p < 0.0001). Non-Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non-Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non Roma children (OR: 1.38, 95% CI: 1.08-1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11-1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non-Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32 6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non-Roma children. PMID- 20573035 TI - Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth. AB - Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG). Here, we study the FLG-associated risk of asthma symptoms in early life and describe the temporal relationship in the development of the different FLG-associated atopic outcomes: asthma, sensitization and eczema, assessed longitudinally from birth. A high-risk cohort of 411 children was assessed in a prospective clinical study from birth to school-age. Asthma, acute severe asthma exacerbations, sensitization and eczema were diagnosed prospectively by the investigators. FLG variants R501X and Del4 were determined in 382 Caucasians. Filaggrin variants increased risk of developing recurrent wheeze, asthma and asthma exacerbations (hazard ratio 1.82 [1.06-3.12], p = 0.03), which was expressed within the first 1.5 yr of life. Children with filaggrin variants had a marked and persistent increase in acute severe asthma exacerbations from 1 yr of age (incidence ratio 2.40 [1.19-4.81], p = 0.01) and increased risk of asthma by age 5 (odds ratio 2.62 [1.12-6.11], p = 0.03). FLG variants increased the risk of eczema, manifesting fully in the first year of life (point prevalence ratio for age 0-5 was 1.75 [1.29-2.37]; p-value = 0.0003) contrasting the increased risk of specific sensitization by age 4 (odds ratio 3.52 [1.72-7.25], p = 0.0007) but not age 1.5. This study describes a FLG associated pattern of atopic diseases characterized by the early onset of asthma symptoms and eczema and later development of sensitization. The association of filaggrin variants with asthma suggests skin barrier dysfunction as a novel, and potentially modifiable, mechanism driving early childhood asthma. PMID- 20573036 TI - Does airway allergic inflammation pre-exist before late onset wheeze in children? AB - Epidemiological studies show that some children develop wheezing after 3 yr of age which tends to persist. It is unknown how this starts or whether there is a period of asymptomatic inflammation. The aim of this study is to determine whether lower airway allergic inflammation pre-exists in late onset childhood wheeze (LOCW). Follow-up study of children below 5 yr who had a non-bronchoscopic bronchoalveolar lavage (BAL) performed during elective surgery. The children had acted as normal controls. A modified ISAAC questionnaire was sent out at least 7 yr following the initial BAL, and this was used to ascertain whether any children had subsequently developed wheezing or other atopic disease (eczema, allergic rhinitis). Cellular and cytokine data from the original BAL were compared between those who never wheezed (NW) and those who had developed LOCW. Eighty-one normal non-asthmatic children were recruited with a median age of 3.2. Of the 65 children contactable, 9 (16.7%) had developed wheeze, 11 (18.5%) developed eczema and 14 (22.2%) developed hay fever. In five patients, wheeze symptoms developed mean 3.3-yr (range: 2-5 yr) post-BAL. Serum IgE and blood eosinophils were not different in the LOCW and NW, although the blood white cell count was lower in the LOCW group. The median BAL eosinophil % was significantly increased in the patients with LOCW (1.55%, IQR: 0.33 to 3.92) compared to the children who never wheezed, NW (0.1, IQR: 0.0 to 0.3, p = 0.01). No differences were detected for other cell types. There were no significant differences in BAL cytokine concentrations between children with LOCW and NW children. Before late onset childhood wheezing developed, we found evidence of elevated eosinophils in the airways. These data suggest pre-existent airways inflammation in childhood asthma some years before clinical presentation. PMID- 20573037 TI - Infant feeding practices and physician diagnosed atopic dermatitis: a prospective cohort study in Taiwan. AB - It is common to recommend breastfeeding and a delayed introduction of solids to prevent atopic dermatitis (AD). However, the scientific evidence for this is inconclusive. The aim of this study was to explore the effect of breastfeeding and solids on AD, when taking account of reverse causality. This on-going birth cohort study was designed to sample 24,200 representative post-partum women and their babies from the Taiwan National Birth Registration database. Using two home interviews at 6 and 18 months after birth, with structured questionnaires about diet and physician's diagnosis of AD by parental reports, a total of 20,172 pairs (83.4%) were reviewed completely. Considering reverse causality, we excluded 2399 children with AD in the first 6 months of life and 18,733 were finally recruited. All study participants provided informed consent as approved by the Ethics Review Board of the National Taiwan College of Public Health. After adjustment for potential confounders, the overall results showed that the increased duration of breastfeeding seemed to increase the risk of AD at 18 months in children. However, no significant effect was found for the delayed introduction of solids on the risk of AD. There is no evidence of a protective effect of prolonged breastfeeding and a delayed introduction of solids against AD among children at age 18 months, and may even be a risk factor of AD. PMID- 20573038 TI - Role of sodium during formation of edema in children with nephrotic syndrome. AB - BACKGROUND: The pathogenesis of edema in nephrotic syndrome is not entirely understood. The aim of this study was to contribute to the discussion on edema pathogenesis in nephrotic syndrome by following changes in volume and sodium retention for the course of the disease in children with steroid-sensitive nephrotic syndrome (SSNS). METHODS: Forty-one children with SSNS were included in the study. The patients were divided into three groups (group I: relapse edematous; group II: relapse-edema free; group III: remission). We investigated the value of the significance and area of sodium retention and vasoactive hormones. In addition, we measured parameters such as inferior vena cava collapsibility index, left atrium diameter, and total body water (TBW) to determine the volume load and cause of edema in children with SSNS. RESULTS: TBW increased in the relapse-nephrotic syndrome group and the difference was statistically significant among groups (P < 0.001). However, inferior vena cava collapsibility index and left atrium diameter were not different among groups. Fractional sodium excretion was lower in children with relapse nephrotic syndrome (P < 0.05). CONCLUSION: Although TBW increases in children with SSNS, intravascular volume is normal. In addition, hypoalbuminemia and sodium retention of the proximal tubule cause edema in children with SSNS. PMID- 20573039 TI - Serum E-selectin levels in Indian children and adolescents: relation to clinical and biochemical parameters. AB - BACKGROUND: An adverse pattern of blood lipids and atherosclerosis begin in childhood. Unfortunately, data for children and adolescents, particularly those in the Indian population, are scarce. The present study aims to evaluate the levels of serum E-selectin in Indian children and adolescents and its correlation with anthropometric and biochemical parameters. METHODS: The study groups included 338 school children and adolescents. There were 96 obese children, 97 overweight children and 42 children with congenital heart disease who were compared with 103 normal controls, aged 10-17 years. Serum E-selectin and serum leptin were analyzed with enzyme-linked immunosorbent assay kits. Lipid profile and fasting glucose were analyzed using an autoanalyzer. RESULTS: Serum E selectin levels were significantly increased in obese (65.3 +/- 8.39 ng/mL) and overweight (56.01 +/- 6.96 ng/mL) subjects (P < 0.001). However, these levels were lower in children with congenital heart disease (40.99 +/- 6.54 ng/mL) than in controls (43.79 +/- 6.71 ng/mL). CONCLUSION: Serum E-selectin levels showed good positive association with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, leptin, total cholesterol, triglycerides and low density lipoprotein cholesterol and showed negative correlation with fasting glucose and no significant association with high-density lipoprotein cholesterol. These findings indicate that higher E-selectin levels can induce endothelial activation and play an essential role in the earliest stage of the atherosclerotic process in obese and overweight children. Regular camps at schools to counsel the identified overweight and obese children and to encourage physical exercise would help to reduce the risk of these children being prone to major cardiovascular anomalies in adulthood. PMID- 20573040 TI - Prophylactic cefdinir for pediatric cases of complicated urinary tract infection. AB - BACKGROUND: This study evaluated the effect of prophylactic cefdinir (3 mg/kg given once daily) for the prevention of recurrent and complicated urinary tract infections (UTI) in pediatric patients. METHODS: The study included 14 infants who were observed for at least 6 months following the first signs of infection (eight boys, six girls; mean age at admission [+/- SD]: 6.2 [+/- 7.4] months). Twelve patients had vesico-ureteric reflux (grade I, two; grade II, three; grade III, six; grade IV, one), and two patients had ureteropelvic junction stenosis. RESULTS: No patients discontinued medication due to diarrhea or other adverse drug reactions. The patients had a 6-month recurrence-free rate of 93% (13/14); only one patient had recurrent UTI. The mean urinary cefdinir concentration was 16.3 [+/- 11.7]ug/mL; there was considerable variability among individual measurements, even though the samples were collected at similar intervals after drug intake (mean 18.00 [+/- 2.63] h after dose). However, the lowest measured urinary cefdinir concentration (1.16 ug/mL) was sufficient to eradicate Escherichia coli, one of the most significant causes of UTI. Fecal cultures, obtained at monthly clinic visits during the observation period, indicated that the patients' E. coli strains were very sensitive to cefdinir. No patients were infected with Pseudomonas aeruginosa or other non-fermenting Gram-negative bacilli or fungi. CONCLUSIONS: These results show that cefdinir given 3 mg/kg once daily is very effective and safe for preventing recurrent complicated UTI in infants. PMID- 20573041 TI - Benign and malignant tumors in Down syndrome: analysis of the 1514 autopsied cases in Japan. AB - BACKGROUND: Down syndrome is known for its association with neoplasms. The aim of this study was to examine this association. METHODS: We surveyed the association with benign and malignant neoplasms in Down syndrome patients registered in the Annual of Pathological Autopsy Cases of Japan (1974-2000), a database of autopsied cases operated by the Japanese Society of Pathology. RESULTS: In a total of 1514 cases with Down syndrome, there were eight cases with 10 benign tumors (four male and four female) and 104 cases with malignant disorders (61 male, 42 female and one case with unrecorded sex), in which 87 cases with hematopoietic malignancies (83.7%) and 17 cases with solid tumors (16.3%), were identified. The association of gallbladder adenocarcinoma with a benign tumor of the colon was noted in one case, while a further two cases with double benign tumors were confirmed as well. No case with a double malignancy was found. Hematopoietic malignancies (87 cases) included 31 cases (35.6%) with acute myelocytic leukemia, 10 (11.4%) with acute lymphocytic leukemia and two (2.3%) with chronic myelocytic leukemia. The ratio of acute myelocytic leukemia to acute lymphocytic leukemia was 3.1 in the present study. A peak in the age distribution was at 0 years in our data in contrast to the previous data (at 1 year) for myelocytic leukemia. The 17 solid tumors identified included three hepatocellular carcinomas, three extrahepatic cholangiocarcinomas, two gallbladder adenocarcinomas, three brain tumors, and three seminomas. CONCLUSION: We present new associations of benign and malignant tumors with Down syndrome. PMID- 20573042 TI - Photo-oxidation of 6-thioguanine by UVA: the formation of addition products with low molecular weight thiol compounds. AB - The thiopurine, 6-thioguanine (6-TG) is present in the DNA of patients treated with the immunosuppressant and anticancer drugs azathioprine or mercaptopurine. The skin of these patients is selectively sensitive to UVA radiation-which comprises >90% of the UV light in incident sunlight-and they suffer high rates of skin cancer. UVA irradiation of DNA 6-TG produces DNA lesions that may contribute to the development of cancer. Antioxidants can protect 6-TG against UVA but 6-TG oxidation products may undergo further reactions. We characterize some of these reactions and show that addition products are formed between UVA-irradiated 6-TG and N-acetylcysteine and other low molecular weight thiol compounds including beta-mercaptoethanol, cysteine and the cysteine-containing tripeptide glutathione (GSH). GSH is also adducted to 6-TG-containing oligodeoxynucleotides in an oxygen and UVA-dependent nucleophilic displacement reaction that involves an intermediate oxidized 6-TG, guanine sulfonate (G(SO3) ). These photochemical reactions of 6-TG, particularly the formation of a covalent oligodeoxynucleotide GSH complex, suggest that crosslinking of proteins or low molecular weight thiol compounds to DNA may be a previously unrecognized hazard in sunlight-exposed cells of thiopurine-treated patients. PMID- 20573043 TI - The hydroxypyridinone iron chelator CP94 can enhance PpIX-induced PDT of cultured human glioma cells. AB - Photodynamic therapy (PDT) with the pro-drugs 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) utilizes the combined interaction of a photosensitizer, light and molecular oxygen to ablate tumor tissue. To potentially increase accumulation of the photosensitizer, protoporphyrin IX (PpIX), within tumor cells an iron chelator can be employed. This study analyzed the effects of ALA/MAL-induced PDT combined with the iron chelator 1, 2-diethyl-3 hydroxypyridin-4-one hydrochloride (CP94) on the accumulation of PpIX in human glioma cells in vitro. Cells were incubated for 0, 3 and 6h with various concentrations of ALA/MAL with or without CP94 and the resulting accumulations of PpIX, which naturally fluoresces, were quantified prior to and following light irradiation. In addition, counts of viable cells were recorded. The use of CP94 in combination with ALA/MAL produced significant enhancements of PpIX fluorescence in human glioma cells. At the highest concentrations of each prodrug, CP94 enhanced PpIX fluorescence significantly at 3h for ALA and by more than 50% at 6h for MAL. Cells subsequently treated with ALA/MAL-induced PDT in combination with CP94 produced the greatest cytotoxicity. It is therefore concluded that with further study CP94 may be a useful adjuvant to photodiagnosis and/or PpIX-induced PDT treatment of glioma. PMID- 20573044 TI - Spore film dosimeters are feasible for UV dose monitoring during heliotherapy. AB - The objective of the study was to compare Bacillus subtilis spore film dosimeters with a Robertson Berger UV meter (RB meter) and diary records for assessing personal UV-B doses during a 13-day heliotherapy (HT) for atopic dermatitis (AD). In addition, the relationship between the personal UV-B dose and change in serum 25-hydroxyvitamin D (25(OH)D) was studied. Altogether 21 adult patients with AD completed the study arranged in the Canary Islands, either in January or March 2005. The spore film dosimeters were used throughout the day during the HT. Serum 25(OH)D was analyzed using radioimmunoassay. The mean personal UV-B dose measured with the dosimeters was 75 SED in January and 131 SED in March. The respective results gained from the RB meter combined with diary records were 63 SED and 119 SED showing a close correlation with the dosimeter results. Serum 25(OH)D concentration increased by 9.7nmol L(-1) in January and by 26.0 7nmol L(-1) in March. The increase in serum 25(OH)D correlated with the UV-B dose received. The patients complied well to use the dosimeters. We conclude spore films to be a feasible and reliable personal UV dosimeter in vivo in field conditions. PMID- 20573045 TI - Histological and microarray analysis of the direct effect of water shortage alone or combined with heat on early grain development in wheat (Triticum aestivum). AB - Based on the in silico analysis of the representation of expressed sequence tags (ESTs) in wheat grain-related cDNA libraries, a specific 15k oligonucleotide microarray has been developed in order to monitor environmental stress-dependent gene expression changes in the wheat caryopses. Using this array, the effect of water withdrawal, with and without additional heat stress, has been investigated during the first five days of kernel development on two wheat cultivars differing in their drought sensitivity. Water shortage affected (more than twofold change) the expression of only 0.5% of the investigated genes. A parallel heat treatment increased the ratio of responding genes to 5-7% because of the temperature stress and/or the increased water deficit because of enhanced evaporation. It could be established that the two cultivars, differing in their long-term adaptation capabilities to drought, responded to the short and direct stress treatments on the same way. In response to the combined drought and heat treatment, the coordinately altered expression of genes coding for storage proteins, enzymes involved in sugar/starch metabolism, histone proteins, heat shock proteins, proteases, tonoplast aquaporins as well as several transcription factors has been observed. These gene expression changes were in agreement with histological data that demonstrated the accelerated development of the embryo as well as the endosperm. PMID- 20573046 TI - Gibberellin-associated cisgenes modify growth, stature and wood properties in Populus. AB - We studied the effects on plant growth from insertion of five cisgenes that encode proteins involved in gibberellin metabolism or signalling. Intact genomic copies of PtGA20ox7, PtGA2ox2,Pt RGL1_1, PtRGL1_2 and PtGAI1 genes from the genome-sequenced Populus trichocarpa clone Nisqually-1 were transformed into Populus tremula * alba (clone INRA 717-1B4), and growth, morphology and xylem cell size characterized in the greenhouse. Each cisgene encompassed 1-2 kb of 5' and 1 kb of 3' flanking DNA, as well as all native exons and introns. Large numbers of independent insertion events per cisgene (19-38), including empty vector controls, were studied. Three of the cisgenic modifications had significant effects on plant growth rate, morphology or wood properties. The PtGA20ox7 cisgene increased rate of shoot regeneration in vitro, accelerated early growth, and variation in growth rate was correlated with PtGA20ox7 gene expression. PtRGL1_1 and PtGA2ox2 caused reduced growth, while PtRGL1_2 gave rise to plants that grew normally but had significantly longer xylem fibres. RT-PCR studies suggested that the lack of growth inhibition observed in PtRGL1_2 cisgenic plants was a result of co-suppression. PtGAI1 slowed regeneration rate and both PtGAI1 and PtGA20ox7 gave rise to increased variance among events for early diameter and volume index, respectively. Our work suggests that cisgenic insertion of additional copies of native genes involved in growth regulation may provide tools to help modify plant architecture, expand the genetic variance in plant architecture available to breeders and accelerate transfer of alleles between difficult-to-cross species. PMID- 20573047 TI - Cl- homeostasis in includer and excluder citrus rootstocks: transport mechanisms and identification of candidate genes. AB - To reveal specific Cl(-) transport activities in the symplastic pathway, uptake, long-distance transport and distribution of Cl(-) have been investigated in the citrus rootstocks Carrizo citrange (CC, Cl(-) includer) and Cleopatra mandarin (CM, Cl(-) excluder). Using an external concentration of 4.5 mm Cl(-) , both species actively transported Cl(-) to levels that exceeded the critical requirement concentration by one and two orders of magnitude in the excluder and the includer rootstocks, respectively. Both CC and CM modulated Cl(-) influx according to the availability of the nutrient as uptake capacity was induced by Cl(-) starvation, but inhibited after Cl(-) resupply. Net Cl(-) uptake was higher in the includer CC, an observation that correlated with a lower root-to-shoot transport capacity in the excluder CM. The patterns of tissue Cl(-) accumulation indicated that chloride exclusion in the salt-tolerant rootstock CM was caused by a reduced net Cl(-) loading into the root xylem. Genes CcCCC1, CcSLAH1 and CcICln1 putatively involved in the regulation of chloride transport were isolated and their expression analysed in response to both changes in the nutritional status of Cl(-) and salt stress. The previously uncharacterized ICln gene exhibited a strong repression to Cl(-) application in the excluder rootstock, suggesting a role in regulating Cl(-) homeostasis in plants. PMID- 20573048 TI - Soil [N] modulates soil C cycling in CO2-fumigated tree stands: a meta-analysis. AB - Under elevated atmospheric CO(2) concentrations, soil carbon (C) inputs are typically enhanced, suggesting larger soil C sequestration potential. However, soil C losses also increase and progressive nitrogen (N) limitation to plant growth may reduce the CO(2) effect on soil C inputs with time. We compiled a data set from 131 manipulation experiments, and used meta-analysis to test the hypotheses that: (1) elevated atmospheric CO(2) stimulates soil C inputs more than C losses, resulting in increasing soil C stocks; and (2) that these responses are modulated by N. Our results confirm that elevated CO(2) induces a C allocation shift towards below-ground biomass compartments. However, the increased soil C inputs were offset by increased heterotrophic respiration (Rh), such that soil C content was not affected by elevated CO(2). Soil N concentration strongly interacted with CO(2) fumigation: the effect of elevated CO(2) on fine root biomass and -production and on microbial activity increased with increasing soil N concentration, while the effect on soil C content decreased with increasing soil N concentration. These results suggest that both plant growth and microbial activity responses to elevated CO(2) are modulated by N availability, and that it is essential to account for soil N concentration in C cycling analyses. PMID- 20573049 TI - AtNHX3 is a vacuolar K+/H+ antiporter required for low-potassium tolerance in Arabidopsis thaliana. AB - Three vacuolar cation/H+ antiporters, AtNHX1 (At5g27150), 2 (At3g05030) and 5 (At1g54370), have been characterized as functional Na+/H+ antiporters in Arabidopsis. However, the physiological functions of AtNHX3 (At5g55470) still remain unclear. In this study, the physiological functions of AtNHX3 were studied using T-DNA insertion mutant and 35S-driven AtNHX3 over-expression Arabidopsis plants. RT-PCR analyses revealed that AtNHX3 is highly expressed in germinating seeds, flowers and siliques. Experiments with AtNHX3::YFP fusion protein in tobacco protoplasts indicated that AtNHX3 is mainly localized to vacuolar membrane, with a minor localization to pre-vacuolar compartments (PVCs) and endoplasmic reticulum (ER). Seedlings of null nhx3 mutants were hypersensitive to K+-deficient conditions. Expression of AtNHX3 complemented the sensitivity to K+ deficiency in nhx3 seedlings. Tonoplast vesicles isolated from transgenic plants over-expressing AtNHX3 displayed significantly higher K+/H+ exchange rates than those isolated from wild-type plants. Furthermore, nhx3 seeds accumulated less K+ and more Na+ when both wild-type and nhx3 were grown under normal growth condition. The overall results indicate that AtNHX3 encodes a K+/H+ antiporter required for low-potassium tolerance during germination and early seedling development, and may function in K+ utilization and ion homeostasis in Arabidopsis. PMID- 20573050 TI - Photosynthesis and metabolism interact during acclimation of Arabidopsis thaliana to high irradiance and sulphur depletion. AB - Arabidopsis plants were exposed to high light or sulphur depletion alone or in combination for 6 d, and changes of photosynthetic parameters and metabolite abundances were quantified. Photosynthetic electron transport rates (ETRs) of plants exposed to sulphur depletion and high light decreased strongly at day 2 of the acclimation period. After 3 d of treatment, the photosynthetic capacity recovered in plants exposed to the combined stresses, indicating a short recovery time for re-adjustment of photosynthesis. However, at metabolic level, the stress combination had a profound effect on central metabolic pathways such as the tricarboxylic acid (TCA) cycle, glycolysis, pentose phosphate cycle and large parts of amino acid metabolism. Under these conditions, central metabolites, such as sugars and their phosphates, increased, while sulphur-containing compounds were decreased. Further differential responses were found for the stress indicator proline accumulating already at day 1 of the high-light regime, but in combination with sulphur depletion first declined and after a recovery phase reached a delayed elevated level. Other metabolites such as raffinose and putrescine seem to replace proline during the early combinatorial stress response and may act as alternative protectants. Our findings support the notion that plants integrate the selectively sensed stress factors in central metabolism. PMID- 20573051 TI - Constitutive salicylic acid defences do not compromise seed yield, drought tolerance and water productivity in the Arabidopsis accession C24. AB - Plants that constitutively express otherwise inducible disease resistance traits often suffer a depressed seed yield in the absence of a challenge by pathogens. This has led to the view that inducible disease resistance is indispensable, ensuring that minimal resources are diverted from growth, reproduction and abiotic stress tolerance. The Arabidopsis genotype C24 has enhanced basal resistance, which was shown to be caused by permanent expression of normally inducible salicylic acid (SA)-regulated defences. However, the seed yield of C24 was greatly enhanced in comparison to disease-resistant mutants that display identical expression of SA defences. Under both water-replete and -limited conditions, C24 showed no difference and increased seed yield, respectively, in comparison with pathogen-susceptible genotypes. C24 was the most drought-tolerant genotype and showed elevated water productivity, defined as seed yield per plant per millilitre water consumed, and achieved this by displaying adjustments to both its development and transpiration efficiency (TE). Therefore, constitutive high levels of disease resistance in C24 do not affect drought tolerance, seed yield and seed viability. This study demonstrates that it will be possible to combine traits that elevate basal disease resistance and improve water productivity in crop species, and such traits need not be mutually exclusive. PMID- 20573052 TI - Case for and against specificity of depression in Alzheimer's disease. AB - AIMS: The aims of this study were to assess the epidemiological, phenomenological, and pathophysiological evidence that suggests the specificity of depression associated with Alzheimer's disease (AD). METHODS: We reviewed the English-language literature. RESULTS: Depression occurs significantly more often in patients with AD than in the general elderly population. While development of depression in response to the disability and emotional stress of AD may be a contributory factor in some patients, several studies showed that depression was not, or was only seldom, related to self-awareness of AD and these studies could not explain the high prevalence figures. To overcome the overlapping phenomenology of the two diseases, specific diagnostic criteria have been developed for depression in this context. Mixed findings have come from neuropathological and neuroimaging studies, with some evidence linking the underlying neural substrate of AD and depression, suggesting an overlapping cause of primary depression and depression comorbid with AD. Few randomized controlled trials for depression associated with AD have been conducted, with rather poor results for the use of antidepressants. CONCLUSIONS: Currently, depression associated with AD is not considered a separate disorder by regulatory authorities and is unlikely to be considered as such in the near future. Several obstacles remain to support such a specific position, including the heterogenous nature of depression in general and within AD itself, the lack of a distinct set of symptoms, and limited treatment. PMID- 20573053 TI - Category verbal fluency predicted changes in behavioral and psychological symptoms of dementia in patients with Alzheimer's disease. AB - AIM: Alzheimer's disease (AD) is characterized by cognitive symptoms and behavioral symptoms, and their association is inconsistent. The aim of this study was to investigate the relationship between cognitive function and the changes in behavioral and psychological symptoms of dementia (BPSD) in patients with AD. METHODS: A total of 101 patients with probable AD were enrolled (57 women and 44 men, mean age 77.6 +/- 7.7 years). The Category Verbal Fluency Test (CVFT), the Mini-Mental State Examination (MMSE), the Constructional Praxis Test, the Delayed Word Recall Test, the Clinical Dementia Rating Scale, and the Neuropsychiatry Inventory (NPI) were administered at baseline. The NPI was reassessed with a median follow-up duration of 10 months (range 6-18 months). The change in the NPI scores was defined as the end-point score of the NPI minus the initial one. The associations between the changes in NPI total score, its four subdomains (hyperactivity, psychosis, affection, and apathy), and cognitive function were examined using multivariate linear models. The results were adjusted for confounders including demographics, baseline NPI, and duration of follow up. RESULTS: The mean MMSE was 18.6 +/- 5.6, the CVFT score was 7.1 +/- 3.9, and the NPI score was 10.9 +/- 13.8. Regression analyses found that the CVFT score (beta = -0.32, P = 0.004) was significantly associated with the change in NPI score, but not the MMSE, the Delayed Word Recall score, or the Constructional Praxis score. The CVFT score was significantly associated with changes in the psychosis subdomain (beta = -0.34, P = 0.001), but not the other subdomains. CONCLUSIONS: Our study showed that CVFT was predictive of the changes in behavior disturbance in patients with AD, particularly in the psychosis domain. PMID- 20573054 TI - Operationalizing proneness to externalizing psychopathology as a multivariate psychophysiological phenotype. AB - The externalizing dimension is viewed as a broad dispositional factor underlying risk for numerous disinhibitory disorders. Prior work has documented deficits in event-related brain potential (ERP) responses in individuals prone to externalizing problems. Here, we constructed a direct physiological index of externalizing vulnerability from three ERP indicators and evaluated its validity in relation to criterion measures in two distinct domains: psychometric and physiological. The index was derived from three ERP measures that covaried in their relations with externalizing proneness-the error-related negativity and two variants of the P3. Scores on this ERP composite predicted psychometric criterion variables and accounted for externalizing-related variance in P3 response from a separate task. These findings illustrate how a diagnostic construct can be operationalized as a composite (multivariate) psychophysiological variable (phenotype). PMID- 20573055 TI - Airway response to emotion- and disease-specific films in asthma, blood phobia, and health. AB - Earlier research found autonomic and airway reactivity in asthma patients when they were exposed to blood-injection-injury (BII) stimuli. We studied oscillatory resistance (R(os)) in asthma and BII phobia during emotional and disease-relevant films and examined whether muscle tension counteracts emotion-induced airway constriction. Fifteen asthma patients, 12 BII phobia patients, and 14 healthy controls viewed one set of negative, positive, neutral, BII-related, and asthma related films with leg muscle tension and a second set without. R(os), ventilation, cardiovascular activity, and skin conductance were measured continuously. R(os) was higher during emotional compared to neutral films, particularly during BII material, and responses increased from healthy over asthmatic to BII phobia participants. Leg muscle tension did not abolish R(os) increases. Thus, the airways are particularly responsive to BII-relevant stimuli, which could become risk factors for asthma patients. PMID- 20573056 TI - Five-year outcome in COPD patients after their first episode of acute exacerbation treated with non-invasive ventilation. AB - BACKGROUND AND OBJECTIVE: Little is known about long-term survival of patients surviving the first episode of type II respiratory failure requiring non-invasive ventilation (NIV). We aimed to determine the 1-, 2- and 5-year survival, cause of death and potential prognostic indicators in this patient cohort. METHODS: We retrospectively identified 100 sequential COPD patients (mean age 70, mean FEV(1) 37% predicted) treated with NIV for the first time. Mortality and data on hospital morbidity and potential prognostic factors were collected from patient records and a State Health Data Linkage Service. RESULTS: Survival at 1, 2 and 5 years was 72%, 52% and 26%, respectively. Respiratory failure secondary to COPD was the commonest cause of death (56.8%), followed by cardiovascular events (25.7%). Readmission rate at 1 year was 60% for those who survived 2 years or more and 52% for those deceased within 2 years. Recurrent respiratory failure requiring NIV was observed in 31% of the cohort. Only advance age (P = 0.04), BMI ( P = 0.014) and prior domiciliary oxygen use (P = 0.03) correlated with death within 5 years. Severity of respiratory failure did not correlate with mortality. CONCLUSIONS: The 2- and 5-year mortality rates for patients with COPD surviving their first episode of respiratory failure requiring NIV are high. Physiological measures of the severity of respiratory failure at presentation do not predict subsequent survival and nor does the time interval between first and second admissions requiring NIV. Age, BMI and prior need for domiciliary oxygen are the main predictors of mortality at 5 years. PMID- 20573057 TI - Pearls and myths in pleural fluid analysis. AB - Virtually all patients with a newly discovered pleural effusion should undergo thoracentesis to aid in diagnosis and management. The routine pleural fluid (PF) evaluation usually includes the following: cell count and differential; tests for protein, LDH, glucose, adenosine deaminase, cytology and, if infection is a concern, pH and bacterial and mycobacterial cultures. Distinguishing transudates from exudates with Light's criteria is a pragmatic first step. If the effusion is an exudate, various PF tests have proven diagnostic utility: adenosine deaminase levels >35 IU/L usually indicate tuberculosis in lymphocyte-predominant PF; pH < 7.2 or glucose less than 60 mg/dL allow the clinician to identify complicated parapneumonic effusions; and conventional cytology may reveal malignant cells in 60% of the patients with malignant effusions. A number of optional PF tests may complement the diagnostic approach to an undiagnosed pleural effusion. For example, natriuretic peptide assays significantly improve the accuracy of a diagnosis of cardiac pleural effusion, whereas PF mesothelin levels greater than 20 nmol/L are highly suggestive of mesothelioma. PMID- 20573058 TI - Occult nodal metastasis in patients with non-small cell lung cancer at clinical stage IA by PET/CT. AB - BACKGROUND AND OBJECTIVE: The introduction of 18F-FDG PET/CT has enhanced the diagnostic accuracy of nodal staging for non-small cell lung cancer (NSCLC). We analysed risk factors for occult nodal metastasis in patients with clinical stage IA NSCLC as determined by 18F-FDG PET/CT. METHODS: Data for 147 patients diagnosed as clinical stage IA NSCLC by PET/CT from 2005 to 2007 were retrospectively reviewed. All study patients underwent 18F-FDG PET/CT for lung cancer staging. They also underwent cervical mediastinoscopy or systematic lymph node dissection. RESULTS: Cervical mediastinoscopy was performed in 78 patients (53.1%), and N2 involvement was detected in 3.8% (3/78) of these patients. Thoracotomy with systematic lymph node dissection was done in 144 patients. Four patients (2.8%, 4/144) were diagnosed with N2 disease after systematic lymph node dissection. Total N2 involvement was 4.8% (7/147). As 9.5% (14/147) of study patients had N1 disease, 14.3% (21/147) of patients had occult nodal (N1 or N2) metastasis. In univariate analyses, larger tumour size and a higher primary tumour maximum standardized uptake value >7.3 (SUV(max)) were associated with occult nodal metastasis. Multivariate analysis demonstrated that a primary tumour SUV(max) >7.3 was an independent predictor of occult nodal metastasis (odds ratio: 7.574; P = 0.001). CONCLUSIONS: Preoperative PET/CT scans contribute to reduce the frequency of occult nodal metastasis compared with those reported in the pre-PET/CT era. The higher SUV(max) in primary tumour was an independent predictor of occult nodal metastasis in patients with clinical stage IA NSCLC by PET/CT. PMID- 20573060 TI - Impact of whole-body 18F-fluorodeoxyglucose positron emission tomography on therapeutic management of non-small cell lung cancer. AB - BACKGROUND AND OBJECTIVE: Accurate staging at the time of diagnosis is very important in deciding on the appropriate treatment for cancer patients. FDG PET indicates metabolic changes in cancer cells, enabling the early detection of lesions. This has the advantage of allowing more accurate staging than is possible with conventional staging tools, and has led to the incorporation of FDG PET in the initial work-up protocols for lung cancer patients. In this study, we evaluated the clinical impact of FDG PET as an initial staging tool, on the therapeutic management of patients with non-small cell lung cancer (NSCLC). METHODS: Patients diagnosed with NSCLC by histopathology were retrospectively identified and both chest CT and FDG PET were performed for initial staging. Information was collected regarding the results of conventional versus FDG PET staging, and any resulting modifications of treatment were evaluated. RESULTS: Among the 537 patients who were evaluated FDG PET resulted in upstaging of the tumour in 91 (17%) and downstaging of the tumour in 68 (13%). Consequently, therapeutic management was modified in 118 patients (22%). Furthermore, use of FDG PET resulted in the detection of a second primary cancer in six patients. CONCLUSIONS: This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC. PMID- 20573059 TI - Clinical profile of adult cystic fibrosis patients with frequent epidemic clones of Pseudomonas aeruginosa. AB - BACKGROUND AND OBJECTIVE: Earlier reports suggested that Pseudomonas aeruginosa frequent epidemic clones circulating in cystic fibrosis (CF) centres had increased virulence. However, recent data show no consistent associations with virulence, and suggest attenuation of virulence in chronic infection. Changes to infection control programmes in relation to frequent epidemic clones should be based on their frequency, virulence across all age groups and mode of acquisition. The Australian epidemic strain-1 (AES-1) (or the Melbourne epidemic strain) and AES-2 are common in CF clinics in mainland eastern Australia, but not in the environment. Both have shown increased virulence, but there are no data specifically in adults. This study examines the frequency and virulence of P. aeruginosa frequent epidemic clones in the adult CF clinic at Royal Prince Alfred Hospital, Sydney, Australia. METHODS: Two hundred and fifty-eight P. aeruginosa isolates from 112 participants were genotyped by pulsed field gel electrophoresis. Ninety-eight patients were followed up for 1 year and associations sought between infection with a frequent epidemic clone, clinical outcome and antibiotic resistance. RESULTS: Four frequent P. aeruginosa epidemic clones (AES-1, AES-2, S-1, S-2) affected almost 50% of participants. AES-1 predominated (38%). AES-1, AES-2 and S-1 were associated with increased exacerbations and hospital-admission days. AES-1 showed increased resistance to aminoglycosides and ticarcillin-clavulanate. CONCLUSIONS: This study supports the potential threat of frequent P. aeruginosa epidemic clones in adult CF populations. PMID- 20573061 TI - Tuberculous mediastinal lymphadenitis that evolved into pulmonary tuberculosis following transbronchial needle aspiration. AB - This case report describes a patient with multi-drug-resistant mediastinal lymph node tuberculosis that evolved to smear-positive pulmonary tuberculosis following transbronchial needle aspiration. This is the first report of this complication, and bronchoscopists should be vigilant for its occurrence. PMID- 20573062 TI - Communicating through caregiver singing during morning care situations in dementia care. AB - It is well known that persons with dementia (PWD) have problems expressing and interpreting communication, making interaction with others difficult. Interaction between PWD and their caregivers is crucial, and several strategies have been investigated to facilitate communication during caregiving. Music therapeutic caregiving (MTC)--when caregivers sing for or together with PWD during caregiving activities--has been shown to enhance communication for PWD, evoking more vitality and positive emotions. The aim of this study was to describe how PWD and their caregivers express verbal and nonverbal communication and make eye contact during the care activity 'getting dressed', during morning care situations without and with MTC. Findings revealed that during the situations without MTC, the caregivers led the dressing procedure with verbal instructions and body movements and seldom invited the PWD to communicate or participate in getting dressed. Patterns in responses to caregivers' instructions included both active and compliant responses and reactions that were resistant and aggressive, confused, and disruptive. In contrast to the 'ordinary' morning care situation, during MTC, the caregivers seemed interested in communicating with the PWD and solicited their mutual engagement. Although verbal communication consisted of singing about things other than getting dressed, e.g. dancing, love, sailing, God, the PWD mostly responded to caregivers in a composed manner, by being active, compliant, and relaxed, though some were also resistant or incongruent. The authors conclude that MTC could be a way for PWD and their caregivers to successfully interact and co-operate during caring situations, as it seems to evoke enhanced communication for both partners in this context. PMID- 20573063 TI - Discovering a new identity after brain injury. AB - Acquired brain injury (ABI) is one example of the chronic conditions that people of varying socioeconomic status must bear. Concerns with identity and self are endemic to surviving brain injury. For this study, a brain tumour survivor injured 17 years earlier, took photographs of her life with brain injury and discussed them with other brain injury survivors and the author. Narrative analysis methods were used to analyse her photographs and interview, and generate a visual illness narrative with four photographs and their accompanying interview text. Her visual illness narrative reveals discovery of a post-brain injury identity whose multiplicity of self-definitions includes chef, brain injury survivor, gardener, and self-advocate. Study findings reveal that identity issues of importance to brain injury survivors can include (1) learning the new, post brain injury self, and (2) building a new identity whose multiple, partial identities include (a) the new brain injured self, (b) an old self (with its residual strengths), and (c) a self who does meaningful activities (e.g. parenting, partnering, art, gardening, volunteering, helping others, or paid work). Study results suggest that using visual research methods can help to put biographical disruption such as brain injury into perspective as a life lived. PMID- 20573064 TI - A new polymorphic position in exon 2 shows the novel allele HLA-DPB1*123:01. AB - Introduction of a novel human leukocyte antigen-DPB1 allele, DPB1*123:01, which featured one nucleotide mismatch in comparison with DPB1*02:01:02. PMID- 20573065 TI - Spatial regulation of Golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity. AB - The enrichment of phosphatidylinositol-4-phosphate (PI(4)P) at the trans Golgi network (TGN) is instrumental for proper protein and lipid sorting, yet how the restricted distribution of PI(4)P is achieved remains unknown. Here, we show that lipid phosphatase Suppressor of actin mutations 1 (SAC1) is crucial for the spatial regulation of Golgi PI(4)P. Ultrastructural analysis revealed that SAC1 is predominantly located at cisternal Golgi membranes but is absent from the TGN, thus confining PI(4)P to the TGN. RNAi-mediated knockdown of SAC1 caused changes in Golgi morphology and mislocalization of Golgi enzymes. Enzymes involved in glycan processing such as mannosidase-II (Man-II) and N-acetylglucosamine transferase-I (GnT-I) redistributed to aberrant intracellular structures and to the cell surface in SAC1 knockdown cells. SAC1 depletion also induced a unique pattern of Golgi-specific defects in N-and O-linked glycosylation. These results indicate that SAC1 organizes PI(4)P distribution between the Golgi complex and the TGN, which is instrumental for resident enzyme partitioning and Golgi morphology. PMID- 20573066 TI - Structural determinants allowing endolysosomal sorting and degradation of endosomal GTPases. AB - Rapid control of protein degradation is usually achieved through the ubiquitin proteasome pathway. We recently found that the short-lived GTPase RhoB is degraded in lysosomes. Moreover, the fusion of the RhoB C-terminal sequence CINCCKVL, containing the isoprenylation and palmitoylation sites, to other proteins directs their sorting into multivesicular bodies (MVBs) and rapid lysosomal degradation. Here, we show that this process is highly specific for RhoB. Alteration of late endosome lipid dynamics produced the accumulation of RhoB, but not of other endosomal GTPases, including Rab5, Rab7, Rab9 or Rab11, into enlarged MVB. Other isoprenylated and bipalmitoylated GTPases, such as H Ras, Rap2A, Rap2B and TC10, were not accumulated into MVB and were stable. Remarkably, although TC10, which is highly homologous to RhoB, was stable, a sequence derived from its C-terminus (CINCCLIT) elicited MVB sorting and degradation of a green fluorescent protein (GFP)-chimeric protein. This led us to identify a cluster of basic amino acids (KKH) in the TC10 hypervariable region, constituting a secondary signal potentially involved in electrostatic interactions with membrane lipids. Mutation of this cluster allowed TC10 MVB sorting and degradation, whereas inserting it into RhoB hypervariable region rescued this protein from its lysosomal degradation pathway. These findings define a highly specific structural module for entering the MVB pathway and rapid lysosomal degradation. PMID- 20573067 TI - gamma-secretase-dependent cleavage initiates notch signaling from the plasma membrane. AB - Notch signaling is critical to animal development, and its dysregulation leads to human maladies ranging from birth defects to cancer. Although endocytosis is currently thought to promote signal activation by delivering activated Notch to endosome-localized gamma-secretase, the data are controversial and the mechanisms that control Notch endocytosis remain poorly defined. Here, we investigated the relationship between Notch internalization and signaling. siRNA-mediated depletion studies reveal that Notch endocytosis is clathrin-dependent and requires epsin1, the adaptor protein complex (AP2) and Nedd4. Moreover, we show that epsin1 interaction with Notch is ubiquitin-dependent. Contrary to the current model, we show that internalization defects lead to elevated gamma secretase-mediated Notch processing and downstream signaling. These results indicate that signal activation occurs independently of Notch endocytosis and that gamma-secretase cleaves Notch at the plasma membrane. These observations support a model where endocytosis serves to downregulate Notch in signal receiving cells. PMID- 20573068 TI - The yeast GRASP Grh1 colocalizes with COPII and is dispensable for organizing the secretory pathway. AB - In mammalian cells, the 'Golgi reassembly and stacking protein' (GRASP) family has been implicated in Golgi stacking, but the broader functions of GRASP proteins are still unclear. The yeast Saccharomyces cerevisiae contains a single non-essential GRASP homolog called Grh1. However, Golgi cisternae in S. cerevisiae are not organized into stacks, so a possible structural role for Grh1 has been difficult to test. Here, we examined the localization and function of Grh1 in S. cerevisiae and in the related yeast Pichia pastoris, which has stacked Golgi cisternae. In agreement with earlier studies indicating that Grh1 interacts with coat protein II (COPII) vesicle coat proteins, we find that Grh1 colocalizes with COPII at transitional endoplasmic reticulum (tER) sites in both yeasts. Deletion of P. pastoris Grh1 had no obvious effect on the structure of tER-Golgi units. To test the role of S. cerevisiae Grh1, we exploited the observation that inhibiting ER export in S. cerevisiae generates enlarged tER sites that are often associated with the cis Golgi. This tER-Golgi association was preserved in the absence of Grh1. The combined data suggest that Grh1 acts early in the secretory pathway, but is dispensable for the organization of secretory compartments. PMID- 20573069 TI - Significance of detecting anti-HBc among Egyptian male blood donors negative for HBsAg. AB - BACKGROUND: Screening for hepatitis B virus surface antigen (HBsAg) reduces the risk of transfusion-transmitted hepatitis B viral (HBV) infection. However, the absence of HBsAg in the blood of apparently healthy individuals may not be sufficient to ensure the lack of circulating HBV. Blood containing anti-hepatitis B core antibody (anti-HBc) without detectable presence of HBsAg might be infectious; therefore, screening for anti-HBc has been implemented in some countries resulting in a decrease in the risk of post-transfusion HBV infection. AIM: To study the seroprevalence of anti-HBc. The relationship between anti-HBc positivity and the presence of circulating HBV among healthy blood donors negative for HBsAg will be helpful to decide whether supplemental testing may bring additional safety to blood products. MATERIAL AND METHODS: A total of 1026 serum samples collected from HBsAg-negative Egyptian healthy male donors were tested for the presence of anti-HBc (both IgM and IgG types) using the competitive enzyme-linked immunosorbent assay technique. Anti-HBc-positive samples were subjected to real-time polymerase chain reaction to confirm the presence of HBV DNA. RESULTS: Of the 1026 samples tested, 80 (7.8%) blood samples were found to be reactive to anti-HBc. Of those, HBV DNA was detected in five of the samples (6.25%). The levels of detected viraemia were variable among the five donors. CONCLUSION: This study shows the insufficient effectiveness of HBsAg screening in protecting blood recipients from HBV infection. Inclusion of anti HBc testing should be considered in the screening of blood donors. PMID- 20573070 TI - Development of a rapid emergency hemorrhage panel. AB - BACKGROUND: Evaluation of hemostasis in bleeding patients requires both accuracy and speed. STUDY DESIGN AND METHODS: As an alternative to point-of-care testing, we developed an emergency hemorrhage panel (EHP: prothrombin time [PT], fibrinogen, platelet count, hematocrit) for use in making transfusion decisions on bleeding patients with a goal of less than 20-minute turnaround time (TAT) when performed in the clinical laboratory on automated instruments. Because point of-care samples are not checked for clotting or hemolysis, we evaluated their effect on automated testing. RESULTS: TAT was reduced by moving the sample immediately to testing and shortening centrifugation times. Clotting in samples was rare (1.1%) and shortened the PT by only 0.7 seconds. It lowered fibrinogen on average 18%, but resulted in only one of 2300 samples changing from normal to low fibrinogen. Hemolysis had no clinically significant effect on the PT or fibrinogen. Therefore, hemolysis checks were eliminated and clot checks minimized. Initially TAT averaged 15+/-4 minutes (range, 8-30min), but 9% of samples exceeded the 20-minute goal due to low fibrinogens that slowed testing. A revised fibrinogen assay with expanded calibration range resulted in a TAT of 14+/-3 minutes (range, 6-28min) with only 2% of samples exceeding the 20-minute goal. By limiting EHPs to patients that were actively bleeding, EHPs accounted for only 8 of 243 coagulation samples per day. CONCLUSION: Limiting EHPs to bleeding patients and modifications to the process and assays used for hemostasis testing lead to TATs of less than 20 minutes for critical testing in the clinical laboratory. PMID- 20573071 TI - Storage age of transfused platelets and outcomes after cardiac surgery. AB - BACKGROUND: The relationship between duration of platelet (PLT) storage, currently limited to 5days, and surgical outcomes has not been established. We tested the hypothesis that PLT storage age was associated with adverse outcomes. STUDY DESIGN AND METHODS: A retrospective cohort of aortocoronary bypass (CABG) surgery patients from January 1996 to January 2005 receiving one or more PLT transfusions was selected for study. The composite primary ("short-term") outcome was 30-day mortality or prolonged hospital stay. Secondary outcomes included complications and survival to annual follow-up. Multivariable logistic regression models and Cox proportional hazards regression analysis evaluated the association between PLT storage age and outcomes, expressed as an odds ratio (OR) or hazard ratio with 95% confidence intervals (CIs), respectively. RESULTS: PLT transfusion was administered to 3272 of 10,275 CABG patients and 2578 received units of known storage age, which ranged between 2 and 5days (median, 4days; 25th percentile, 3days; 75th percentile, 5 days). The mortality rate for the 1637 patients receiving a single plateletpheresis transfusion was 3.8%, while 21.6% experienced a prolonged hospital stay or death. After adjusting for the number of PLT and red blood cell (RBC) units transfused, RBC storage age, and preoperative mortality risk, there was no association between PLT storage age and short-term outcome (OR, 1.01; 95% CI, 0.90-1.14), survival (hazard ratio [HR], 1.04; 95% CI, 0.96 1.13), or postoperative infections. CONCLUSIONS: PLT storage age was not associated with adverse short-term outcomes, decreased long-term survival, or infections after cardiac surgery. PMID- 20573072 TI - Fucose-deficient hematopoietic stem cells have decreased self-renewal and aberrant marrow niche occupancy. AB - BACKGROUND: Modification of Notch receptors by O-linked fucose and its further elongation by the Fringe family of glycosyltransferase has been shown to be important for Notch signaling activation. Our recent studies disclose a myeloproliferative phenotype, hematopoietic stem cell (HSC) dysfunction, and abnormal Notch signaling in mice deficient in FX, which is required for fucosylation of a number of proteins including Notch. The purpose of this study was to assess the self-renewal and stem cell niche features of fucose-deficient HSCs. STUDY DESIGN AND METHODS: Homeostasis and maintenance of HSCs derived from FX(-/-) mice were studied by serial bone marrow transplantation, homing assay, and cell cycle analysis. Two-photon intravital microscopy was performed to visualize and compare the in vivo marrow niche occupancy by fucose-deficient and wild-type (WT) HSCs. RESULTS: Marrow progenitors from FX(-/-) mice had mild homing defects that could be partially prevented by exogenous fucose supplementation. Fucose-deficient HSCs from FX(-/-) mice displayed decreased self renewal capability compared with the WT controls. This is accompanied with their increased cell cycling activity and suppressed Notch ligand binding. When tracked in vivo by two-photon intravital imaging, the fucose-deficient HSCs were found localized farther from the endosteum of the calvarium marrow than the WT HSCs. CONCLUSIONS: The current reported aberrant niche occupancy by HSCs from FX(-/-) mice, in the context of a faulty blood lineage homeostasis and HSC dysfunction in mice expressing Notch receptors deficient in O-fucosylation, suggests that fucosylation-modified Notch receptor may represent a novel extrinsic regulator for HSC engraftment and HSC niche maintenance. PMID- 20573073 TI - Cryopreservation of peripheral blood stem cell: the influence of cell concentration on cellular and hematopoietic recovery. AB - BACKGROUND: The optimal cryopreservation cell concentration during the peripheral blood stem cell (PBSC) collection is a controversial topic. We evaluated the influence of cryopreservation concentration on the recovery of hematopoietic progenitor cells and the kinetics of hematopoietic recovery of autologous stem cell transplant patients. STUDY DESIGN AND METHODS: In this retrospective study, we compared two different cryopreservation protocols: 1*10(8) cells/mL (Protocol A) and 2*10(8) cells/mL (Protocol B). A total of 419 PBSCs were analyzed with regard to the number of viable cells and colony-forming units-granulocytes monocytes (CFU-GM) progenitors. The hematopoietic recovery of 275 patients who received PBSCs cryopreserved at a dose of 1*10(8) cells/mL (Group A) and 2*10(8) cells/mL (Group B) were compared. RESULTS: There were no significant differences in recovery of viable cells between Protocol A and Protocol B. The median of recovery of CFU-GM progenitors was significantly higher in Protocol B (41.2 vs. 57.3, p<0.01). The median times to neutrophil recovery (>=500*10(6) /L) and platelet (PLT) recovery (>=20*10(9) /L) in Groups A and B were 11 days versus 11 days and 12 days versus 12 days, respectively. However, by Kaplan and Meier analyses, Group B recovered neutrophils with a little delay (p=0.01). No difference was observed with regard to time to PLT recovery. On multivariate analysis, we found that the number of CD34+ cells and CFU-GM progenitors had a significant influence on hematopoietic recovery. CONCLUSION: Cryopreservation of PBSCs at a dose of 2*10(8) cells/mL did not affect the recovery rate of viable cells or the hematopoietic recovery of autologous stem cell transplant patients. PMID- 20573074 TI - Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion-transmitted hepatitis B virus infection in Switzerland, a low-endemic region. AB - BACKGROUND: The risk of transfusion-transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti-HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual-donation (ID)-NAT (Ultrio assay on Tigris system, Gen Probe/Novartis Diagnostics). ID-NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti-HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti-HBc and HBsAg was retrospectively estimated in a mathematical model. RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti-HBc positive, respectively. Seven HBV-NAT yields were identified (1:44,000), two pre-HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID-NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti-HBc. The data from this study led to the decision to introduce sensitive HBV-NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost effective HBV screening strategies in low-prevalence countries. PMID- 20573075 TI - Diagnosis of cryptococcal and tuberculous meningitis in a resource-limited African setting. AB - OBJECTIVES: Cryptococcal meningitis (CM) and tuberculous meningitis (TBM) are common in HIV-infected adults in Africa and difficult to diagnose. Inaccurate diagnosis results in adverse outcomes. We describe patterns of meningitis in a Malawian hospital, focusing on features which differentiate CM and TBM with the aim to derive an algorithm using only clinical and basic laboratory data available in this resource-poor setting. METHODS: Consecutive patients admitted with meningitis were prospectively recruited, clinical features were recorded and cerebrospinal fluid (CSF) was examined. RESULTS: A total of 573 patients were recruited, and 263 (46%) had CSF consistent with meningitis. One hundred and twelve (43%) had CM and 46 (18%) had TBM. CM was associated with high CSF opening pressure and low CSF leukocyte count. Fever, neck stiffness and reduced conscious level were associated with TBM. A diagnostic index was constructed demonstrating sensitivity 83%and specificity 79% for the differentiation of CM and TBM. An algorithm was derived with 92% sensitivity for the diagnosis of CM, but only 58% specificity. CONCLUSIONS: Although we demonstrate features associated with CM and TBM, a sufficiently sensitive and specific diagnostic algorithm could not be derived, suggesting that the diagnosis of CM and TBM in resource-limited settings still requires better access to laboratory tools. PMID- 20573076 TI - Dysrhythmias associated with cocaine overdose. PMID- 20573077 TI - Icatibant. PMID- 20573079 TI - Putting cocaine use and cocaine-associated cardiac arrhythmias into epidemiological and clinical perspective. AB - This is the first article in a series of three articles on cocaine-related cardiac arrhythmias, following on from the 2008 British Pharmacological Society Winter Meeting Clinical Section Symposium entitled 'Cocaine induced cardiac arrhythmias - from ion channel to clinical treatment'. We will summarize the epidemiology of cocaine use across the world and in particular will focus on UK, Europe and US use prevalence data. We will discuss the acute cardiac and non cardiac toxicity associated with cocaine and highlight the lack of data on the true UK prevalence of acute cocaine toxicity and on the incidence of cocaine related cardiac arrhythmias. PMID- 20573078 TI - Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias. AB - Cocaine is a highly active stimulant that alters dopamine metabolism in the central nervous system resulting in a feeling of euphoria that with time can lead to addictive behaviours. Cocaine has numerous deleterious effects in humans including seizures, vasoconstriction, ischaemia, increased heart rate and blood pressure, cardiac arrhythmias and sudden death. The cardiotoxic effects of cocaine are indirectly mediated by an increase in sympathomimetic stimulation to the heart and coronary vasculature and by a direct effect on the ion channels responsible for maintaining the electrical excitability of the heart. The direct and indirect effects of cocaine work in tandem to disrupt the co-ordinated electrical activity of the heart and have been associated with life-threatening cardiac arrhythmias. This review focuses on the direct effects of cocaine on cardiac ion channels, with particular focus on sodium, potassium and calcium channels, and on the contributions of these channels to cocaine-induced arrhythmias. Companion articles in this edition of the journal examine the epidemiology of cocaine use (Wood & Dargan) and the treatment of cocaine associated arrhythmias (Hoffmann). PMID- 20573080 TI - Treatment of patients with cocaine-induced arrhythmias: bringing the bench to the bedside. AB - Widespread use of cocaine and its attendant toxicity has produced a wealth of benchwork studies and small animal investigations that evaluated the effects of cocaine on the cardiovascular system. Despite this wealth of knowledge, very little is known about the frequency or types of arrhythmias in patients with significant cocaine toxicity. The likely aetiologies; catecholamine excess, sodium channel blockade, potassium channel blockade, calcium channel effects, or ischaemia may act alone or in concert to produce a vast array of clinical findings that are modulated by hyperthermia, acidosis, hypoxia and electrolyte abnormalities. The initial paper in the series by Wood & Dargan providing the epidemiological framework of cocaine use and abuse is followed by a detailed review of the electrophysiological effects of cocaine by O'Leary & Hancox. This review is designed to complement the previous papers and focuses on the diagnosis and treatment of patients with cocaine-associated arrhythmias. PMID- 20573081 TI - Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study. AB - AIM: Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction. METHODS: This double blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 microg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine). RESULTS: Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean +/- SD AUC (l kPa(-1) h) for placebo 24.4 +/- 4.37, for 50 microg 29.0 +/- 7.08, for 300 microg 31.2 +/- 6.68 and for 600 microg 32.7 +/- 7.95) (P < 0.009), except 50 microg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 microg compared with placebo at all assessments (Raw mean +/- SD AUC (kPa s(-1) l(-1) h) for placebo 7.7 +/- 3.46, for 300 microg 5.8 +/- 2.33, for 600 microg 6.3 +/- 3.11) (P < 0.04) except 600 microg at 24 h. Differences between aclidinium 300 and 600 microg vs. placebo in PC35 doubling concentration were significant at all assessments (mean +/- SD AUC (mg ml(-1) h) for placebo 100.0 +/- 30.27, for 50 microg 117.2 +/- 33.33, for 300 microg 168.9 +/- 28.66 and for 600 microg 179.1 +/- 15.73 (P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 microg and the higher doses (P < 0.0001). Aclidinium was not detected in plasma and was well tolerated. CONCLUSION: Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD. PMID- 20573082 TI - Population pharmacokinetics of intravenously and orally administered docetaxel with or without co-administration of ritonavir in patients with advanced cancer. AB - AIM: Docetaxel has a low oral bioavailability due to affinity for P-glycoprotein and cytochrome P450 (CYP) 3A4 enzymes. Inhibition of the CYP3A4 enzymes by ritonavir resulted in increased oral bioavailability. The aim of this study was to develop a population pharmacokinetic (PK) model and to evaluate and quantify the influence of ritonavir on the PK of docetaxel. METHODS: Data from two clinical trials were included in the data analysis, in which docetaxel (75 mg m( 2) or 100 mg) had been administered intravenously or orally (10 mg or 100 mg) with or without co-administration of oral ritonavir (100 mg). Population modelling was performed using non-linear mixed effects modelling. A three compartment model was used to describe the i.v. data. PK data after oral administration, with or without co-administration of ritonavir, were incorporated into the model. RESULTS: Gut bioavailability of docetaxel increased approximately two-fold from 19 to 39% (CV 13%) with ritonavir co-administration. The hepatic extraction ratio and the elimination rate of docetaxel were best described by estimating the intrinsic clearance. Ritonavir was found to inhibit in a concentration dependent manner the intrinsic clearance of docetaxel, which was described by an inhibition constant of 0.028 microg ml(-1) (CV 36%). A maximum inhibition of docetaxel clearance of more then 90% was reached. CONCLUSIONS: A PK model describing both the PK of orally and intravenously administered docetaxel in combination with ritonavir, was successfully developed. Co-administration of ritonavir lead to increased oral absorption and reduced elimination rate of docetaxel. PMID- 20573083 TI - Intracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patients. AB - AIM: To study the steady-state plasma and intracellular pharmacokinetics of raltegravir, etravirine, darunavir and ritonavir in heavily pre-treated patients. METHODS: Patients on a salvage regimen containing raltegravir, etravirine, darunavir and ritonavir were eligible for inclusion. During a 12 h dosing interval plasma and peripheral blood mononuclear cells were collected. Drug concentrations were measured using a validated LC-MS/MS assay and pharmacokinetic analysis was performed using non-linear mixed effect modelling. RESULTS: Irregular absorption was observed with raltegravir and darunavir, which may be caused by enterohepatic cycling. Relative bioavailability of ritonavir was low, when compared with other ritonavir regimens. Raltegravir plasma pharmacokinetics showed wide interpatient variability, while intracellular raltegravir concentrations could not be detected (<0.001 mg l(-1) in cell lysate). The intracellular to plasma ratios for etravirine, darunavir and ritonavir were 12.9, 1.32 and 7.72, respectively, and the relative standard error of these estimates were 16.3%, 12.3% and 13.0%. CONCLUSIONS: The observed distinct intracellular accumulation indicated that these drugs have different affinity for the cellular compartment. The relatively high intracellular accumulation of etravirine may explain its efficacy and its previously described absence of PK-PD relationships in the therapeutic concentration range, when compared with other non-nucleoside reverse transcriptase inhibitors. Lastly, the intracellular concentrations of ritonavir seem sufficient for inhibition of viral replication in the cellular compartment in PI-naive patients, but not in patients with HIV harbouring PI resistance. PMID- 20573084 TI - Population pharmacokinetics of melphalan in patients with multiple myeloma undergoing high dose therapy. AB - AIMS: To i) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach, ii) identify clinical factors that affect melphalan disposition and iii) evaluate the role of melphalan exposure in melphalan-related toxicity and disease response. METHODS: Population pharmacokinetic modelling (using NONMEM) was performed with total and unbound concentration-time data from 100 patients (36-73 years) who had received a median 192 mg m(-2) melphalan dose. Model derived estimates of total and unbound melphalan exposure (AUC) in patients with serious melphalan toxicity and those who had a good disease response (>or=90% decrease in paraprotein concentrations) were compared using the Mann-Whitney test. RESULTS: A two compartment model generated population mean estimates for total and unbound melphalan clearance (CL) of 27.8 and 128 l h(-1), respectively. Estimated creatinine clearance, fat free mass and haematocrit were important determinants of total and unbound CL, reducing the inter-individual variability in total CL from 34% to 27% and in unbound CL from 42% to 30%. Total AUC (range 4.9-24.4 mg l(-1) h) and unbound AUC (range 1.0-6.5 mg l(-1) h) were significantly higher in patients who had oral mucositis (>or=grade 3) and long hospital admissions (P < 0.01). Patients who responded well had significantly higher unbound AUC (median 3.2 vs. 2.8 mg l(-1) h, P < 0.05) when assessed from diagnosis to post-melphalan and higher total AUC (median 21.3 vs. 13.4 mg l(-1) h, P= 0.06), when assessed from pre- to post melphalan. CONCLUSIONS: Creatinine clearance, fat free mass and haematocrit influence total and unbound melphalan plasma clearance. Melphalan exposure is related to melphalan toxicity while the association with efficacy shows promising trends that will be studied further. PMID- 20573085 TI - Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. AB - AIM: Gabapentin enacarbil, a transported prodrug of gabapentin, provides sustained, dose-proportional exposure to gabapentin. Unlike gabapentin, the prodrug is absorbed throughout the intestinal tract by high-capacity nutrient transporters, including mono-carboxylate transporter-1 (MCT-1). Once absorbed, gabapentin enacarbil is rapidly hydrolyzed to gabapentin, which is subsequently excreted by renal elimination via organic cation transporters (OCT2). To examine the potential for drug-drug interactions at these two transporters, the pharmacokinetics of gabapentin enacarbil were evaluated in healthy adults after administration alone or in combination with either naproxen (an MCT-1 substrate) or cimetidine (an OCT2 substrate). METHODS: Subjects (n= 12 in each study) received doses of study drug until steady state was achieved; 1200 mg gabapentin enacarbil each day, followed by either naproxen (500 mg twice daily) or cimetidine (400 mg four times daily) followed by the combination. RESULTS: When gabapentin enacarbil was co-administered with naproxen, gabapentin C(ss,max) increased by, on average, 8% and AUC by, on average, 13%. When gabapentin enacarbil was co-administered with cimetidine, gabapentin AUC(ss) increased by 24% and renal clearance of gabapentin decreased. Co-administration with gabapentin enacarbil did not affect naproxen or cimetidine exposure. Gabapentin enacarbil was generally well tolerated. CONCLUSIONS: No gabapentin enacarbil dose adjustment is needed with co-administration of naproxen or cimetidine. PMID- 20573086 TI - Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. AB - AIMS: This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. METHODS: This was an open-label, randomized, three-treatment, cross-over, clinical trial in healthy male subjects (n= 12) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre-treatment with each herbal medicine at recommended doses. Pharmacodynamic (INR, platelet activity) and pharmacokinetic (warfarin enantiomer concentrations) end points were evaluated. RESULTS: The apparent clearance of (S)-warfarin (90% CI of ratio; 1.01, 1.18) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinically significant change in INR (90% CI of AUC of INR; 0.91, 1.31). Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response. Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre treatment with the respective herbal medicines. CONCLUSION: Echinacea significantly reduced plasma concentrations of S-warfarin. However, neither echinacea nor policosanol significantly affected warfarin pharmacodynamics, platelet aggregation or baseline clotting status in healthy subjects. PMID- 20573087 TI - Omeprazole-induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype. AB - AIM: Omeprazole-induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS: Twenty patients were genotyped for the CYP2C19 variant alleles (2, 681G>A and 3, 636G>A) by RFLP-PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS: The frequency of the CYP2C19 2 allelic variant was 12.5%, no 3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS: There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN. PMID- 20573088 TI - Current dosing of low-molecular-weight heparins does not reflect licensed product labels: an international survey. AB - AIMS: Low-molecular-weight heparins (LMWHs) are used globally to treat thromboembolic diseases; however, there is much debate on how to prescribe effectively for patients who have renal impairment and/or obesity. We aimed to investigate the strategies used to dose-individualize LMWH therapy. METHODS: We conducted an online survey of selected hospitals in Australia, New Zealand (NZ), United Kingdom (UK) and the United States (US). Outcome measures included: the percentage of hospitals which recommended that LMWHs were prescribed according to the product label (PL), the percentage of hospitals that dose-individualized LMWHs outside the PL based on renal function, body weight and anti-Xa activity and a summary of methods used to dose-individualize therapy. RESULTS: A total of 257 surveys were suitable for analysis: 84 (33%) from Australia, 79 (31%) from the UK, 73 (28%) from the US and 21 (8%) from NZ. Formal dosing protocols were used in 207 (81%) hospitals, of which 198 (96%) did not adhere to the PL. Of these 198 hospitals, 175 (87%) preferred to dose-individualize based on renal function, 128 (62%) on body weight and 48 (23%) by monitoring anti-Xa activity. All three of these variables were used in 29 (14%) hospitals, 98 (47%) used two variables and 71 (34%) used only one variable. CONCLUSIONS: Dose individualization strategies for LMWHs, which contravene the PL, were present in 96% of surveyed hospitals. Common individualization methods included dose capping, use of lean body size descriptors to calculate renal function and the starting dose, followed by post dose anti-Xa monitoring. PMID- 20573089 TI - Correlates of spontaneous reporting of adverse drug reactions within primary care: the paradox of low prescribers who are high reporters. AB - AIM(S): To examine Primary Care Trust (PCT) demographics influencing general practitioner (GP) involvement in pharmacovigilance. METHODS: PCT adverse drug reaction (ADR) reports to the Yellow Card scheme between April 2004 and March 2006 were obtained for the UK West Midlands region. Reports were analysed by all drugs, and most commonly reported drugs ('top drugs'). PCT data, adjusted for population size, were aggregated. Prescribing statistics and other characteristics were obtained for each PCT, and associations between these characteristics and ADR reporting rates were examined. RESULTS: During 2004-06, 1175 reports were received from PCTs. Two hundred and eighty (24%) of these reports were for 14 'top drugs'. The mean rate of reporting for PCTs was 213 reports per million population. A total of 153 million items were prescribed during 2004-06, of which 33% were 'top drugs'. Reports for all drugs and 'top drugs' were inversely correlated with the number of prescriptions issued per thousand population (r(s)=-0.413, 95% CI -0.673, -0.062, P < 0.05, and r=-0.420, 95% CI -0.678, -0.071, P < 0.05, respectively). Reporting was significantly negatively correlated with the percentages of male GPs within a PCT, GPs over 55 years of age, single-handed GPs within a PCT, the average list size of a GP within a PCT, the overall deprivation scores and average QOF total points. ADR reports did not correlate significantly with the proportion of the population over 65 years old. CONCLUSIONS: Some PCT characteristics appear to be associated with low levels of ADR reporting. The association of low prescribing areas with high ADR reporting rates replicates previous findings. PMID- 20573090 TI - Medication use as a risk factor for inpatient falls in an acute care hospital: a case-crossover study. AB - AIMS: The present study aimed to evaluate the associations between medication use and falls and to identify high risk medications that acted as a trigger for the onset of falls in an acute care hospital setting. METHODS: We applied a case crossover design wherein cases served as their own controls and comparisons were made within each participant. The 3-day period (days 0 to -2) and the 3-day periods (days -6 to -8, days -9 to -11 and days -12 to -14) before the fall event were defined as the case period and the control periods, respectively. Exposures to medications were compared between the case and control periods. Odds ratios (OR) and 95% confidence intervals (CI) for the onset of falls with respect to medication use were computed using conditional logistic regression analyses. RESULTS: A total of 349 inpatients who fell during their hospitalization were recorded on incident report forms between March 2003 and August 2005. The initial use of antihypertensive, antiparkinsonian, anti-anxiety and hypnotic agents as medication classes was significantly associated with an increased risk of falls, and these ORs (95% CI) were 8.42 (3.12, 22.72), 4.18 (1.75, 10.02), 3.25 (1.62, 6.50) and 2.44 (1.32, 4.51), respectively. The initial use of candesartan, etizolam, biperiden and zopiclone was also identified as a potential risk factor for falls. CONCLUSIONS: Medical professionals should be aware of the possibility that starting a new medication such as an antihypertensive agent, including candesartan, and antiparkinsonian, anti-anxiety and hypnotic agents, may act as a trigger for the onset of a fall. PMID- 20573091 TI - Potentially inappropriate prescribing and cost outcomes for older people: a national population study. AB - AIMS: Optimization of drug prescribing in older populations is a priority due to the significant clinical and economic costs of drug-related illness. This study aimed to: (i) estimate the prevalence of potentially inappropriate prescribing (PIP) in a national Irish older population using European specific explicit prescribing criteria; (ii) investigate the association between PIP, number of drug classes, gender and age and; (iii) establish the total cost of PIP. METHODS: This was a retrospective national population study (n= 338 801) using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. The HSE-PCRS uses the WHO Anatomical Therapeutic Chemical (ATC) classification system and details of every drug dispensed and claimants' demographic data are available. Thirty PIP indicators (STOPP) were applied to prescription claims for those >or=70 years in Ireland in 2007. STOPP is a physiological system based screening tool of older persons' potentially inappropriate prescriptions assessing drug-drug and drug-disease interactions, dose and duration. RESULTS: In our study population PIP prevalence was 36% (121 454 claimants). The main contributors to this were: 56 560 (17%) prescribed proton pump inhibitors at maximum therapeutic dose for >8 weeks, 29 691 (9%) prescribed non-steroidal anti-inflammatories for >3 months, 17 676 (5%) prescribed long-acting benzodiazepines for >1 month and 16 201 (5%) prescribed duplicate drugs. The main determinant of PIP was polypharmacy. The likelihood of PIP increased with a significant linear and quadratic trend (P < 0.0001) with the number of drug classes.The maximum net ingredient cost of PIP was estimated to be euro38 664 640. Total PIP expenditure was estimated to be euro45 631 319, 9% of the overall expenditure on pharmaceuticals in those >or=70 years in 2007. CONCLUSIONS: The findings identify a high prevalence of PIP in Ireland with significant cost consequences. PMID- 20573092 TI - The recording of drug sensitivities for older people living in care homes. AB - AIMS: The aims of this study were to determine the recording of drug sensitivities of elderly care home residents, to describe the nature of sensitivities and to identify and describe discrepancies in the documentation of drug sensitivity status in general practices, pharmacies and care homes. METHODS: A random sample of residents within a purposive sample of care homes (nursing and residential) was selected. A clinical pharmacist inspected the GP medical record, the medicines administration record, and the care home record for each resident to identify drug sensitivities and discrepancies between records and to describe the nature of the recorded sensitivities. RESULTS: The records of 121 residents in 31 care homes were studied. Thirty-one (26%) residents had at least one documented drug sensitivity in one of the sources inspected, with 48 sensitivities in total recorded. There was no description of the nature of the sensitivities recorded in 39/48 (81%) cases. The number of sensitivities recorded on the medicines administration record, care home record and the GP record were 3 (6%), 29 (60%) and 35 (73%), respectively. Only two sensitivities were simultaneously recorded on all three records. CONCLUSIONS: It was of concern that over 90% of drug sensitivities were not recorded on the medicines administration record which is the final checking document when administering medication. The reason for this was that the dispensing pharmacy was responsible for generating the medicines administration record; however, drug sensitivity status is seldom shared between the GP and the dispensing pharmacy. Printing sensitivities on prescriptions would help to resolve this. PMID- 20573093 TI - Acute liver damage due to Serenoa repens: a case report. PMID- 20573094 TI - Anticholinergics, antimuscarinics or atropinics? About the words in pharmacology. PMID- 20573097 TI - Integrating different perspectives on socialization theory and research: a domain specific approach. AB - There are several different theoretical and research approaches to the study of socialization, characterized by frequently competing basic tenets and apparently contradictory evidence. As a way of integrating approaches and understanding discrepancies, it is proposed that socialization processes be viewed from a domain perspective, with each domain characterized by a particular form of social interaction between the object and agent of socialization and by specific socialization mechanisms and outcomes. It is argued that this approach requires researchers to identify the domain of social interaction they are investigating, to understand that phenotypically similar behaviors may belong to different domains, and to acknowledge that caregivers who are effective in one type of interaction may not be effective in another. PMID- 20573098 TI - Commentary and challenges to Grusec and Davidov's domain-specific approach. AB - J. E. Grusec and M. Davidov's article (this issue) about domains of parenting and their links with different aspects of childhood outcome raises both interesting questions and challenges. Four of these concerns are discussed in relation to early childhood. First is the issue of bidirectionality. Recent studies highlight the contribution of individual differences in children, and of dyadic measures that include both child and parent, to the quality of parent-child relationships. Second, the specification of domains can be problematic, given the evidence of overlap between domains, and of combinations of different domains in real-life interactions. Third, developmental issues need to be addressed, as do cultural and cohort influences. Finally, children need to be considered as family members who monitor interactions between other family members, learn from and influence these others. The challenge to their account posed by models of family environments that include effects not shared by siblings merit attention. PMID- 20573099 TI - Modules, theories, or islands of expertise? Domain specificity in socialization. AB - The domain-specific approach to socialization processes presented by J. E. Grusec and M. Davidov (this issue) provides a compelling framework for integrating and interpreting a large and disparate body of research findings, and it generates a wealth of testable new hypotheses. At the same time, it introduces core theoretical questions regarding the nature of social interactions, from the perspective of both children and their caregivers. This commentary draws on the literature regarding domain specificity in cognitive development, applauds what is innovative and exciting about applying a domain-specific approach to socialization processes, and points to questions for future research. Foremost among these is what is meant by "domain specificity." PMID- 20573100 TI - Domain specificity in social interactions, social thought, and social development. AB - J. E. Grusec and M. Davidov (this issue) have taken good steps in formulating a domain-specific view of parent-child interactions. This commentary supports the introduction of domain specificity to analyses of parenting. Their formulation is an advance over formulations that characterized parental practices globally. This commentary calls for inclusion of definitions of the classification system of domain-specific interactions and criteria for each domain. It is also maintained that Grusec and Davidov's domains of social interaction imply that processes of development are involved, along with socialization; that bidirectionality in parent-child relations needs to be extended to include mutual influences and the construction of domains of social thought; and that conflicts and opposition within families coexist with compliance and social harmony. PMID- 20573101 TI - Connecting cues: overlapping regularities support cue discovery in infancy. AB - The present work examined the discovery of linguistic cues during a word segmentation task. Whereas previous studies have focused on sensitivity to individual cues, this study addresses how individual cues may be used to discover additional, correlated cues. Twenty-four 9-month-old infants were familiarized with a speech stream in which syllable-level transitional probabilities and an overlapping novel cue served as cues to word boundaries. Infants' behavior at test indicated that they were able to discover the novel cue. Additional experiments showed that infants did not have a preexisting preference for specific test items and that transitional probability information was necessary to acquire the novel cue. Results suggest one way learners can discover relevant linguistic structure amid the multiple overlapping properties of natural language. PMID- 20573103 TI - The development of social essentialism: the case of israeli children's inferences about jews and arabs. AB - Two studies examined the inductive potential of various social categories among 144 kindergarten, 2nd-, and 6th-grade Israeli children from 3 sectors: secular Jews, religious Jews, and Muslim Arabs. Study 1-wherein social categories were labeled-found that ethnic categories were the most inductively powerful, especially for religious Jewish children. Study 2-wherein no social category labels were provided-found no differences across sectors either in the inductive potential of ethnic categories or in children's capacity to visually recognize social categories. These results stress the importance of labels and cultural background in children's beliefs about social categories. The implications of these findings for accounts of the development of social essentialism are discussed. PMID- 20573102 TI - Do effects of early child care extend to age 15 years? Results from the NICHD study of early child care and youth development. AB - Relations between nonrelative child care (birth to 4(1/2) years) and functioning at age 15 were examined (N = 1,364). Both quality and quantity of child care were linked to adolescent functioning. Effects were similar in size as those observed at younger ages. Higher quality care predicted higher cognitive-academic achievement at age 15, with escalating positive effects at higher levels of quality. The association between quality and achievement was mediated, in part, by earlier child-care effects on achievement. High-quality early child care also predicted youth reports of less externalizing behavior. More hours of nonrelative care predicted greater risk taking and impulsivity at age 15, relations that were partially mediated by earlier child-care effects on externalizing behaviors. PMID- 20573104 TI - Gender, values, and occupational interests among children, adolescents, and adults. AB - Work fulfills personal values, perhaps differently for males and females. Explored here was the role values play in shaping occupational interests. Study 1 examined children's, adolescents', and adults' (N = 313) occupational values (regarding money, power, family, altruism), occupational interests, and perceptions of values afforded by traditionally masculine and feminine occupations. Results revealed sex differences in occupational values and interests. Furthermore, participants' values predicted their own interests in culturally masculine and feminine occupations. Study 2 used novel jobs and experimentally manipulated prototypical sex of worker and value affordances to disentangle their effects on occupational interests. At all ages, participants' (N = 240) occupational interests were affected by the depicted sex of the workers and by the stated value affordances of the jobs. PMID- 20573105 TI - The head bone's connected to the neck bone: when do toddlers represent their own body topography? AB - Developments in very young children's topographic representations of their own bodies were examined. Sixty-one 20- and 30-month-old children were administered tasks that indexed the ability to locate specific body parts on oneself and knowledge of how one's body parts are spatially organized, as well as body-size knowledge and self-awareness. Age differences in performance emerged for every task. Body-part localization and body spatial configuration knowledge were associated; however, body topography knowledge was not associated with body-size knowledge. Both were related to traditional measures of self-awareness, mediated by their common associations with age. It is concluded that children possess an explicit, if rudimentary, topographic representation of their own body's shape, structure, and size by 30 months of age. PMID- 20573106 TI - I like me if you like me: on the interpersonal modulation and regulation of preadolescents' state self-esteem. AB - This experiment tested whether peer approval and disapproval experiences can cause immediate change in children's state self-esteem. Children's narcissistic traits and evaluator perceived popularity were examined as potential moderators. A total of 333 preadolescents (M = 10.8 years) completed personal profiles on the Internet that were ostensibly judged by a jury consisting of popular and unpopular peers. Participants randomly received negative, neutral, or positive feedback from the jury. Next, they could examine the feedback that each individual judge gave them. As expected, peer disapproval decreased self-esteem, especially in children high in narcissism. In contrast, peer approval increased self-esteem. Moreover, disapproved children's self-esteem recovery was dependent on the extent to which they subsequently viewed positive feedback from popular judges. These findings support sociometer theory. PMID- 20573107 TI - Individual and peer group normative beliefs about relational aggression. AB - Studies show that children who use relational aggression process social information in unique ways; however, findings have been inconsistent and limited by methodological weaknesses. This short-term longitudinal study examined developmental changes in 245 (49% female; ages 8-13) 3rd through 8th graders' normative beliefs about relational aggression and tested the hypothesis that individual and classroom-level norms predict relational aggression 1 year later. Results showed that the transition to middle school was marked by increased approval of relational aggression, and individual norms predicted future relational aggression. Importantly, a contextual model showed that students in peer groups highly supportive of relational aggression became increasingly aggressive. Findings extend social information processing theories of relational aggression to focus on the role of peer group cognitions. PMID- 20573108 TI - Antecedents and correlates of the popular-aggressive phenomenon in elementary school. AB - This study identified correlates and developmental antecedents that distinguish popular-aggressive elementary school children from other youth. Drawing on the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (N = 1022), popular-aggressive children were identified through teacher ratings over Grades 3-6. Potential correlates included social competence as rated by observers, mothers, and teachers. Potential developmental antecedents included cognitive functioning, maternal sensitivity, and participation in child care through age 4.5. Multinomial regressions allowed for the determination of group differences net of covariates such as gender, ethnicity, maternal education, and income-to-needs. Results showed that popular aggressive elementary school children were distinguished from other youth as having had an extensive child-care history. Discussion focuses on developmental associations between child-care quantity and aggression. PMID- 20573109 TI - The rise in cortisol in family day care: associations with aspects of care quality, child behavior, and child sex. AB - This study examined the increase in salivary cortisol from midmorning to midafternoon in 151 children (3.0-4.5 years) in full-time home-based day care. Compared to cortisol levels at home, increases were noted in the majority of children (63%) at day care, with 40% classified as a stress response. Observations at day care revealed that intrusive, overcontrolling care was associated with the cortisol rise. For girls, the cortisol rise was associated with anxious, vigilant behavior, while for boys the rise was associated with angry, aggressive behavior. Child behavior did not mediate or moderate relations between care quality and the cortisol rise, except for evidence that boys scoring low on angry, aggressive behavior were more sensitive to variations in warm, supportive care than boys scoring high on this behavior. PMID- 20573110 TI - Children's sleep and adjustment over time: the role of socioeconomic context. AB - Relations were examined between children's sleep and their externalizing and internalizing symptoms. Longitudinal relations were examined when children were in 3rd (T1) and 5th (T2) grades, and cross-sectional relations were assessed at T2. Participants included 176 children at T1 (M = 8.68 years) and 141 children at T2 (M = 10.70 years). Sleep was examined via subjective reports and actigraphy. Children reported on anxiety, self-esteem, and depression symptoms, and parents reported on children's externalizing and internalizing symptoms. Cross sectionally and longitudinally, sleep problems were associated with worse adjustment outcomes; African American children or those from lower socioeconomic status homes were at particular risk. Findings highlight the importance of adequate sleep for children's optimal development, especially in the context of ecological risk. PMID- 20573111 TI - Experience-based and on-line categorization of objects in early infancy. AB - What processes do infants employ in categorizing? Infants might categorize on line as they encounter category-related entities; alternatively, infants might depend on prior experience with entities in formulating categories. These alternatives were tested in forty-four 5-month-olds. Infants who were familiarized in the laboratory with a category of never-before-seen objects subsequently treated novel objects of the same category as familiar-they categorized on line-just as did infants who were exposed to objects from the same category at home for 2 months leading to their laboratory assessment of object categorization. Infants with home experience also recognized novel category objects as familiar from the outset-that is, prior experience with category exemplars was brought to bear in laboratory tasks. PMID- 20573112 TI - Mexican-heritage children's attention and learning from interactions directed to others. AB - The study builds on ethnographic research noting an emphasis in many Indigenous communities of the Americas on learning through keen observation of and participation in ongoing community activities. Forty-four U.S. Mexican-heritage 5 to 11-year-old children whose families likely have experience with Indigenous ways more frequently attended to and learned from a toy construction activity that was directed to another child, compared to 36 U.S. Mexican-heritage children whose mothers had extensive experience with Western school (and related European American practices). The results support the idea that children whose family history emanates from Indigenous communities of Mexico may be especially oriented to learning by observing ongoing events, and that this method of learning may be less commonly used by children whose families have extensive experience with schooling (and related Western practices). PMID- 20573113 TI - Children's understanding of social-cognitive and social-communicative aspects of discourse irony. AB - To bridge the social-reasoning focus of developmental research on irony understanding and the pragmatic focus of research with adult populations, this cross-sectional study examines 5-, 7-, and 9-year-olds' (n = 72) developing understanding of both social-cognitive and social-communicative aspects of discourse irony, when compared with adults (n = 24). Although 5-year-olds lag behind the other age groups in their reasoning about the speaker's meaning, belief, intention, and motivation, adults are consistently superior to children of all ages on these social-cognitive measures. In contrast, limited age-related differences were found in participants' judgment of the social-communicative function of irony (how nice, mean, and funny irony is). The findings help to reconcile previous discrepant claims as to the age when children come to understand irony. PMID- 20573114 TI - Inconsistency with prior knowledge triggers children's causal explanatory reasoning. AB - What events trigger causal explanatory reasoning in young children? Children's explanations could be triggered by either consistent events (suggesting that explanations serve a confirmatory function) or inconsistent events (suggesting that they promote discovery of new information). In 2 studies with preschool children (N = 80), events that were consistent with children's prior knowledge were simultaneously contrasted with events that were inconsistent with prior knowledge, and children were invited to explain either outcome (or both). Results demonstrate that inconsistent outcomes are an especially powerful trigger for children's explanations and that the explanations children provide for inconsistent outcomes refer to internal causal properties, overriding perceptual appearances. In sum, the data provide empirical evidence that inconsistent events motivate children to construct explanations, thereby suggesting that children's explanations function in the service of discovery. PMID- 20573115 TI - Children's Tattling: the reporting of everyday norm violations in preschool settings. AB - Tattling, defined as the reporting to a second party of norm violations committed by a third party, is a frequent but little-studied activity among young children. Participant observation and quantitative sampling are used to provide a detailed characterization of tattling in 2 preschools (initial mean age = 4.08 years, N = 40). In these populations, tattling represents the majority of talk about peers' behavior to third parties. It is usually truthful, it rarely refers to transgressions committed against other individuals, it is not often ignored by adults, it is performed more frequently by dominant children, and it correlates with teacher reports of relational aggression. These exploratory results suggest several new avenues of research into children's developing understanding of social norms. PMID- 20573116 TI - Conversation, development, and gender: a study of changes in children's concepts of punishment. AB - One hundred thirty-three children, average age 9.58 years, were read vignettes describing a moral transgression and then discussed what would constitute a fair punishment. Children's gender influenced conversation dynamics (use of interruption and other simultaneous speech) but not conversation content (justifications for judgments). All children who engaged in conversation showed development in judgments after 8 weeks compared with a control (no interaction) group. However, there was no relation between conversation dynamics or content and development, or any effects of gender, on the developmental process. The benefits of peer collaboration were general rather than specific to the stimulus story. PMID- 20573117 TI - Family socioeconomic status and consistent environmental stimulation in early childhood. AB - The transition into school occurs at the intersection of multiple environmental settings. This study applied growth curve modeling to a sample of 1,364 American children, followed from birth through age 6, who had been categorized by their exposure to cognitive stimulation at home and in preschool child care and 1st grade classrooms. Of special interest was the unique and combined contribution to early learning of these 3 settings. Net of socioeconomic selection into different settings, children had higher math achievement when they were consistently stimulated in all 3, and they had higher reading achievement when consistently stimulated at home and in child care. The observed benefits of consistent environmental stimulation tended to be more pronounced for low-income children. PMID- 20573118 TI - Parent involvement and children's academic and social development in elementary school. AB - Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Childcare and Youth Development (N = 1,364) were used to investigate children's trajectories of academic and social development across 1st, 3rd, and 5th grades. Hierarchical linear modeling was used to examine within and between-child associations among maternal and teacher reports of parent involvement and children's standardized achievement scores, social skills, and problem behaviors. Findings suggest that within-child improvements in parent involvement predict declines in problem behaviors and improvements in social skills but do not predict changes in achievement. Between-child analyses demonstrated that children with highly involved parents had enhanced social functioning and fewer behavior problems. Similar patterns of findings emerged for teacher and parent reports of parent involvement. Implications for policy and practice are discussed. PMID- 20573119 TI - The dynamics of free recall and their relation to rehearsal between 8 and 10 years of age. AB - The present study longitudinally examined changes in recall in children between the ages of 8 and 10 years. Given the increasingly sophisticated use of memory strategies during this developmental period, correspondences between study and recall dynamics were of particular interest. Seventy-six children performed free recall tasks on 5 occasions over a 2-year period. Video and audio analyses revealed that children tended to recall items successively from nearby serial positions. This so-called lag-recency effect was particularly pronounced when items from nearby serial positions were conjunctly rehearsed during study. Implications for understanding study-recall correspondences are discussed in relation to other developmental changes of this period including memory capacity. PMID- 20573122 TI - Climate change is the norm! Why focus on just one pop-problem at a time--energy, mould, sustainability or climate change? When is the time for real indoor air and health science? PMID- 20573123 TI - Field study on behaviors and adaptation of elderly people and their thermal comfort requirements in residential environments. AB - This study investigated the thermal sensation of elderly people in Taiwan, older than 60 years, in indoor microclimate at home, and their requirements for establishing thermal comfort. The study was conducted using both a thermal sensation questionnaire and measurement of indoor climatic parameters underlying the thermal environment. Survey results were compared with those reported by Cheng and Hwang (2008, J. Tongji Univ., 38, 817-822) for non-elders to study the variation between different age groups in requirements of indoor thermal comfort. The results show that the predominant strategy of thermal adaptation for elders was window-opening in the summer and clothing adjustment in the winter. The temperature of thermal neutrality was 25.2 degrees C and 23.2 degrees C for the summer and the winter, respectively. Logistically regressed probit modeling on percentage of predicted dissatisfied (PPD) against mean thermal sensation vote revealed that the sensation votes corresponding to a PPD of 20% were +/- 0.75 for elders, about +/- 0.10 less than the levels projected by ISO 7730 model. The range of operative temperature for 80% thermal acceptability for elders in the summer was 23.2-27.1 degrees C, narrower than the range of 23.0-28.6 degrees C reported for non-elders. This is likely a result of a difference in the selection of adaptive strategies. PRACTICAL IMPLICATIONS: Taiwan in the last decade has seen a rapid growth in the elderly population in its societal structure, and as such the quality of indoor thermal comfort increasingly concerns the elderly people. This study presents the results from field-surveying elders residing in major geographical areas of Taiwan, and discusses the requirements of these elders for indoor thermal comfort in different seasons. Through a comparison with the requirements by non-elders, this study demonstrates the unique sensitivity of elders toward indoor thermal quality and the selection of adaptive strategies that need to be considered when a thermal comfort zone is attempted in a household of members consisting of different age groups. PMID- 20573124 TI - Efficacy of photocatalytic HEPA filter on microorganism removal. AB - This study assessed the application of photocatalytic oxidation (PCO) to the high efficiency particulate air (HEPA) filter for disinfection of airborne microorganisms. Experiments were conducted at two TiO2 loadings (1870 +/- 169 and 3140 +/- 67 mg/m(2)) on the HEPA filter irradiated with UV-A at the intensity of 0.85 +/- 0.18 or 4.85 +/- 0.09 mW/cm(2) under two relative humidity conditions (45 +/- 5% and 75 +/- 5%). Inactivation and penetration of four microorganisms were tested, including Aspergillus niger, Penicillium citrinum, Staphylococcus epidermidis, and Bacillus subtilis. It was found that microorganisms retained on a photocatalytic filter were inactivated around 60-80% and even 100% for S. epidermidis when the PCO reactions occurred. Lower penetration was also found from the photocatalytic filter for all airborne microorganisms. High humidity decreased photocatalysis efficacy. Increasing TiO2 loading or irradiance intensity did not substantially affect its disinfection capability. PRACTICAL IMPLICATIONS: The high efficiency particulate air filter is used widely to remove particulates and microorganisms from the air stream. However, the filter may become a source of microbes if those retained microorganisms proliferate and re entrain back into the filtered air. This study demonstrates that such a problem can be handled effectively by using photocatalytic reactions to inactivate those confined microorganisms. A 60-100% microbe reduction can be achieved for a wide variety of microorganisms to provide better indoor air quality for hospitals, offices, and domestic applications. PMID- 20573125 TI - Can a photocatalytic air purifier be used to improve the perceived air quality indoors? AB - The effect of a photocatalytic air purifier on perceived air quality (PAQ) was examined in rooms polluted by typical sources of indoor pollution. The rooms were ventilated at three different outdoor air supply rates. The air quality was assessed by a sensory panel when the purifier was in operation as well as when it was off. Operation of the purifier significantly improved PAQ in the rooms polluted by building materials (used carpet, old linoleum, and old chipboard), and a used ventilation filter as well as a mixture of building materials, used ventilation filter and cathode-ray tube computer monitors. The effect corresponded to approximately doubling the outdoor air supply rate. Operation of the purifier significantly worsened the PAQ in rooms with human bioeffluents, probably due to incomplete oxidation of alcohols which are one of the main pollutants emitted by humans. Present results show that the photocatalytic air purifier can supplement ventilation when the indoor air is polluted by building related sources, but should not be used in spaces where human bioeffluents constitute the main source of pollution. PRACTICAL IMPLICATIONS: The present results suggest that a photocatalytic air purifier can supplement ventilation when the indoor air is polluted mainly by building-related sources, for example in unoccupied buildings outside working hours when ventilation is considerably reduced or turned off and pollutants build up and adsorb on indoor surfaces. The results also suggest that use of a photocatalytic air purifier should be avoided when humans are present and constitute main source of pollution. PMID- 20573126 TI - Distribution and fate of polybrominated diphenyl ethers in indoor environments of elementary schools. AB - Polybrominated diphenyl ethers (PBDEs) are considered harmful to human health because of their toxicities and persistence in environments. In the current study, the distribution and fate of PBDEs in classrooms and computer rooms in 17 elementary schools in South Korea have been described. Eight congeners (brominated diphenyl ether-28, -47, -99, -100, -153, -154, -183, and -209) in air, floor dust, and product surface dust were measured. While Sigma(8)PBDEs in the air in classrooms showed considerable variations (0.659-1600 pg/m(3), arithmetic mean +/- s.d.: 377 +/- 441 pg/m(3)), those in computer rooms were somewhat similar (134-220 pg/m(3), arithmetic mean +/- s.d.: 169 +/- 40 pg/m(3)). Sigma(8)PBDEs in floor dust varied over a wide range, from 453 to 45,700 ng/g, for all rooms. Based on congener patterns, two groups were created--CL-1 that is dominated by high-brominated congeners and CL-2 primarily comprising low brominated congeners--for both air and floor dust of classrooms. Surface dust had low concentrations, ranged from ND to 181, from ND to 128, and from ND to 256 pg/cm(2) for desk/chair sets, lockers, and playing tools, respectively. Pearson correlation coefficients were calculated individually for air, floor dust, and surface dust. The results indicate that both surface dust and floor dust may act as a secondary source of PBDEs in indoor environments after emission from facilities. PRACTICAL IMPLICATIONS: Children have been estimated to have a higher potential exposure to PBDEs than adults. Since children spend most of their day time at school, PBDE distributions in school environments should be a matter of great concern. PMID- 20573128 TI - Dimensions of normal and abnormal personality: elucidating DSM-IV personality disorder symptoms in adolescents. AB - The present study aimed to elucidate dimensions of normal and abnormal personality underlying DSM-IV personality disorder (PD) symptoms in 168 adolescents referred to mental health services. Dimensions derived from the Big Five of normal personality and from Livesley's (2006) conceptualization of personality pathology were regressed on interview-based DSM-IV PD symptom counts. When examined independently, both models demonstrated significant levels of predictive power at the higher order level. However, when added to the higher order Big Five dimensions, Livesley's higher and lower order dimensions afforded a supplementary contribution to the understanding of dysfunctional characteristics of adolescent PDs. In addition, they contributed to a better differentiation between adolescent PDs. The present findings suggest that adolescent PDs are more than extreme, maladaptive variants of higher order normal personality traits. Adolescent PDs seem to encompass characteristics that may be more completely covered by dimensions of abnormal personality. Developmental issues and implications of the findings are discussed. PMID- 20573129 TI - Approach and avoidance temperament as basic dimensions of personality. AB - This research comprises 6 studies designed to examine approach and avoidance temperament as basic dimensions of personality. In Study 1, we developed direct measures of approach and avoidance temperament. In Study 2, we demonstrated that the approach and avoidance temperament variables are not epiphenomena of response biases. In Study 3, we documented the test-retest stability of the temperament variables. In Study 4, we documented that approach and avoidance temperament are separate from other like-valenced variables and may be construed as the core of these variables. In Study 5, we documented that approach and avoidance temperament are separate from chronic promotion and prevention foci. In Study 6, we distinguished the temperament variables from achievement goal variables and documented the temperament variables as antecedents of achievement goals and achievement goals as proximal predictors of performance. Approach and avoidance temperament are discussed as an ideal foundation for a strong, enduring structure of personality. PMID- 20573127 TI - The validity and structure of culture-level personality scores: data from ratings of young adolescents. AB - We examined properties of culture-level personality traits in ratings of targets (N=5,109) ages 12 to 17 in 24 cultures. Aggregate scores were generalizable across gender, age, and relationship groups and showed convergence with culture level scores from previous studies of self-reports and observer ratings of adults, but they were unrelated to national character stereotypes. Trait profiles also showed cross-study agreement within most cultures, 8 of which had not previously been studied. Multidimensional scaling showed that Western and non Western cultures clustered along a dimension related to Extraversion. A culture level factor analysis replicated earlier findings of a broad Extraversion factor but generally resembled the factor structure found in individuals. Continued analysis of aggregate personality scores is warranted. PMID- 20573130 TI - Varieties of moral personality: beyond the banality of heroism. AB - Four perspectives dominate thinking about moral heroism: One contends that moral action is primarily instigated by situational pressures, another holds that moral excellence entails the full complement of virtues, the third asserts a single superintending principle, and the fourth posits different varieties of moral personality. This research addresses these competing perspectives by examining the personalities of moral heroes. Participants were 50 national awardees for moral action and 50 comparison individuals. They responded to personality inventories and a life-review interview that provided a broadband assessment of personality. Cluster analysis of the moral exemplars yielded three types: a "communal" cluster was strongly relational and generative, a "deliberative" cluster had sophisticated epistemic and moral reasoning as well as heightened self-development motivation, and an "ordinary" cluster had a more commonplace personality. These contrasting profiles imply that exemplary moral functioning can take multifarious forms and arises from different sources, reflecting divergent person x situation interactions. PMID- 20573131 TI - What makes the political personal? Openness, personal political salience, and activism. AB - People who attach personal meaning to social and political events or are high in Personal Political Salience (PPS) are more likely to engage in political activism (Duncan & Stewart, 2007). Although research suggests that PPS is consequential for activism, we know little about its origins or, more generally, about indirect effects of personality on activism. In this study we examined the possibility that the personality trait of Openness to Experience may be one source of PPS and an indirect predictor of activism. In addition, we proposed that Openness would also be directly related to political activism in young adults but not in middle aged and older adults. Analyses confirmed these predictions in cross-sectional and over-time data from six samples. We argue that Openness may predispose some individuals both to find personal meaning in distant political events and to engage in social activism in their youth. PMID- 20573132 TI - Structured terror: further exploring the effects of mortality salience and personal need for structure on worldview defense. AB - Previous research indicates that people respond to heightened death-related cognition with increased defense of predominant cultural beliefs (cultural worldview defense). However, recent research indicates that individual differences in personal need for structure (PNS) impact responses to threatening thoughts of death such that those high, but not low, in PNS respond to death thoughts by seeking a highly structured, clear, and coherent view of the world. Research has yet to fully consider the extent to which PNS affects the cultural worldview defenses typically exhibited after death is rendered salient. The current 3 studies examine the potential for PNS to determine the extent to which people respond to mortality salience with increased worldview defense. In all three studies PNS was measured and mortality salience induced. Subsequently, university-related (Study 1) or religious (Studies 2 and 3) worldview defense was assessed. Only individuals high in PNS responded to mortality salience with increased worldview defense. PMID- 20573133 TI - Approach/positive anticipation, frustration/anger, and overt aggression in childhood. AB - We examined mothers' ratings of children's affective and behavioral aspects of approach tendencies and links with overt aggressive behavior problems while considering the genetic etiology of these processes. Approach/positive anticipation (AP), frustration/anger (FA), and overt aggression in 4-9-year-olds were assessed using mothers' reports in a diverse national sample (n=992) and a sample of same-sex twins (n=195 pairs). AP and FA were positively correlated with each other and with overt aggression (r from .2 to .5), and these associations were very similar for boys and girls. AP and FA provided overlapping as well as independent statistical prediction of aggression. AP statistical prediction of aggression was substantially mediated by FA, an effect that was accounted for by underlying genetic and nonshared environmental influences. PMID- 20573134 TI - Interpersonal circumplex descriptions of psychosocial risk factors for physical illness: application to hostility, neuroticism, and marital adjustment. AB - Personality risk factors for physical illness are typically studied individually and apart from risk factors reflecting the social environment, potentially fostering a piecemeal understanding of psychosocial influences on health. Because it can be used to describe both personality and social relationship processes, the interpersonal circumplex (IPC) provides an integrative approach to psychosocial risk. In 301 married couples we examined IPC correlates of 3 risk factor domains: anger, hostility, and aggressiveness; neuroticism; and marital adjustment. Risk factors displayed IPC locations ranging from hostile dominance (e.g., verbal aggressiveness, marital conflict) to hostility (e.g., anger) to hostile submissiveness (e.g., anxiety, depression); protective factors (marital satisfaction and support) reflected warmth or friendliness in the IPC. Similar descriptions were found using self-reports and spouse ratings of IPC dimensions, indicating that interpersonal styles associated with risk factors do not simply reflect common method variance. Findings identify interpersonal processes reflecting low affiliation or high hostility as a common component of risk and indicate distinctions among risk factors along the dominance dimension. PMID- 20573135 TI - To have or to be? A comparison of materialism-based theories and self determination theory as explanatory frameworks of prejudice. AB - The present study aimed to delineate the psychological structure of materialism and intrinsic and extrinsic value pursuit. Moreover, we compared models based on self-determination theory (SDT), Fromm's marketing character, and Inglehart's theory of social change to account for racial prejudice. In a sample of undergraduate students (n=131) and adults (n=176) it was revealed that the extrinsic value pursuit Financial Success/Materialism could be distinguished from the extrinsic value scales Physical Appeal and Social Recognition, and Community Concern could be distinguished from the intrinsic value pursuit scales Self acceptance and Affiliation. Moreover, Financial Success/Materialism and Community Concern were consistently and significantly related to prejudice, whereas the other SDT facet scales yielded weaker relationships with prejudice. Structural models based on SDT and Inglehart were not corroborated, but instead the present data supported a mediation model based on Fromm's work in which the effect of Community Concern was mediated by Financial Success/Materialism. Broader implications for SDT are critically assessed. PMID- 20573136 TI - Personality and defensive reactions: fear, trait anxiety, and threat magnification. AB - The revised Reinforcement Sensitivity Theory (rRST) of personality (Gray & McNaughton, 2000) maintains that trait individual differences in the operation of defensive systems relate to facets of human personality, most notably anxiety and fear. We investigated this theory in 2 separate studies (total N=270) using a threat scenario research strategy (Blanchard, Hynd, Minke, Minemoto, & Blanchard, 2001). Consistent with rRST, results showed that individuals with high fear questionnaire scores tended to select defensive responses entailing orientation away from threat (e.g., run away) and that fear-prone individuals also tended to perceive threats as magnified. The extent of this threat magnification mediated the positive association observed between fear and orientation away from threat. Overall, results suggest that interindividual variance in defensive reactions is associated with a variety of existing personality constructs but that further research is required to determine the precise relationship between personality and defensive reactions. PMID- 20573138 TI - Students and school adults: partners in keeping schools safe. PMID- 20573140 TI - School policies and practices that improve indoor air quality. AB - BACKGROUND: To determine whether schools with a formal indoor air quality management program were more likely than schools without a formal program to have policies and practices that promote superior indoor air quality. METHODS: This study analyzed school-level data from the 2006 School Health Policies and Programs Study, a national study of school health programs and policies at the state, district, and school levels. Using chi-square analyses, the rates of policies and practices that promote indoor air quality were compared between schools with and schools without a formal indoor air quality program. RESULTS: The findings of this study show that 51.4% of schools had a formal indoor air quality management program, and that those schools were significantly more likely than were schools without a program to have policies and use strategies to promote superior indoor air quality. CONCLUSIONS: These findings suggest that schools with a formal indoor air quality program are more likely support policies and engage in practices that promote superior indoor air quality. PMID- 20573139 TI - Student and teacher perceptions of school climate: a multilevel exploration of patterns of discrepancy. AB - BACKGROUND: School climate has been linked with improved academic achievement and reduced discipline problems, and thus is often a target of school improvement initiatives. However, few studies have examined the extent to which student and teacher perceptions vary as a function of individual, classroom, and school characteristics, or the level of congruence between teachers' and their students' perceptions of school climate. METHODS: Using data from 1881 fifth-grade students and their 90 homeroom teachers, we examined parallel models of students' and teachers' perceptions of overall school climate and academic emphasis. Two additional models were fit that assessed the congruence between teacher and student perceptions of school climate and academic emphasis. RESULTS: Multilevel analyses indicated that classroom-level factors were more closely associated with teachers' perceptions of climate, whereas school-level factors were more closely associated with the students' perceptions. Further analyses indicated an inverse association between student and teacher ratings of academic emphasis, and no association between student and teacher ratings of overall climate. CONCLUSIONS: Teacher ratings were more sensitive to classroom-level factors, such as poor classroom management and proportion of students with disruptive behaviors, whereas student ratings were more influenced by school-level factors such as student mobility, student-teacher relationship, and principal turnover. The discrepancy in ratings of academic emphasis suggests that while all of the respondents may have shared objectively similar experiences, their perceptions of those experiences varied significantly. These results emphasize the importance of assessing both student and teacher perceptions in future research on school climate. PMID- 20573141 TI - Using the information-motivation behavioral model to predict sexual behavior among underserved minority youth. AB - BACKGROUND: Testing, refining, and tailoring theoretical approaches that are hypothesized to reduce sexual risk behaviors among adolescent subpopulations is an important task. Relatively little is known about the relationship between components of the information-motivation-behavior (IMB) model and sexual behaviors among underage minority youth. Using the IMB model, this study examines predictors of risky sexual behavior among underserved Hispanic and African American youth. METHODS: This cross-sectional study was conducted with a sample of 380 youths aged 11-17 years recruited in Los Angeles, California, and utilized latent variable models to examine interrelationships and predictive relations among IMB model variables associated with risky sexual behavior. RESULTS: Sixty percent of the participants aged 15-17 and 1 out of 10 participants aged 11-12 reported prior sexual intercourse. Of the sexually active, more than half reported having unprotected sex and 11% had sexual intercourse with 4 or more partners. Results of the structural equation model indicated that older age and attitudes against sexual activities had significant, direct impacts on risky sexual behaviors. Behavioral refusal skills, positioned as an intervening variable, also significantly predicted less risky sex. Knowledge, attitudes against sexual activities, and perceived peer pressure against sexual behavior predicted sexual refusal skills. Additionally, there were significant indirect effects on risky sexual behavior mediated through behavioral refusal skills. CONCLUSION: A large number of disadvantaged minority urban youth are engaged in risky sexual behaviors. Intervention programs, particularly those targeting preadolescents, should focus on building long-lasting behavioral skills that emphasize the reduction of peer pressure and normative influences on risky sexual behaviors. Components of the IMB model clearly have a role in the design of efficacious interventions. PMID- 20573142 TI - Associations between poor health and school-related behavior problems at the child and family levels: a cross-sectional study of migrant children and adolescents in southwest urban China. AB - BACKGROUND: Due to urbanization in China, the numbers of migrant children and adolescents in urban environments have increased. Previous studies have indicated that children and adolescents are more likely to suffer from health problems and poor school achievement. The present study identified associations between poor health and school-related behavior problems (ie, learning attitudes and learning disabilities [LL], antisocial behavior and risk behavior [AR], and social adaptation and role function [SR]) at the child and family levels. METHODS: A cross-sectional design was used. Seven hundred and eighty-one participants were recruited in inclusive settings. Correlational analysis was conducted to assess the associations between demographic variables and the primary study variables. Logistic regression analysis was used to determine which study factors were the strongest predictors of general health problems. RESULTS: School-aged migrants who had poorer health tended to be more likely to suffer from school-related behavior problems. Poor health was also found to hinder scholastic achievement in migrant children and adolescents through a higher prevalence of school-related behavior problems, including negative learning attitudes and learning disabilities, antisocial behavior and risk behavior, and social maladjustment. Health risk factors included inappropriate parental education methods, fewer classmates, and less social support. CONCLUSIONS: Health and individual risk factors should be explored further to determine their causal role in migrant children and adolescents with school-related behavior problems. These results have implications for future school health education for these students. PMID- 20573143 TI - A comparison of mail and telephone administration of district-level questionnaires for the School Health Policies and Programs Study (SHPPS) 2006: effects on estimates and data quality. AB - BACKGROUND: The School Health Policies and Programs Study (SHPPS) is a national study periodically conducted to assess school health policies and programs at the state, district, school, and classroom levels. For SHPPS 2006, district-level questionnaires were designed for telephone administration, but mixed-mode data collection that also used paper-and-pencil mail questionnaires was required to obtain an acceptable response rate. Because most mode effect research has involved person-level rather than institution-level data, little is known about the effects of mixed-mode data collection on data quality and prevalence estimates obtained through surveys of school personnel. METHODS: SHPPS 2006 used 1-stage stratified cluster sampling to select a nationally representative sample of public school districts. Personnel in about half of the 538 responding districts completed paper questionnaires and returned them via mail. Analyses were performed comparing data quality and prevalence estimates for mail and telephone administration. RESULTS: Prevalence estimates for only 7.0% (39) of 554 questions tested across the 7 questionnaires differed significantly by response mode at the p < .01 level. Regarding data quality, use of the "don't know" response was higher for telephone administration. CONCLUSIONS: The results of this study demonstrate that SHPPS 2006 successfully used a mixed-mode approach, allowing the data to be used without concern about the mixed-mode administration. The results may also be useful to other researchers interested in using surveys to collect data on schools or school districts or other data that is not person level. PMID- 20573144 TI - School nurses' perceptions and practices of assisting students in obtaining public health insurance. AB - BACKGROUND: From January through June 2009, 6.1 million children were uninsured in the United States. On average, students with health insurance are healthier and as a result are more likely to be academically successful. Some schools help students obtain health insurance with the help of school nurses. METHODS: This study assessed public school nurses' knowledge and beliefs of the impact of health insurance on students' health and academic success. The study also determined whether public school nurses or their schools were involved in helping students obtain public health insurance, and if so, how they did so. Additionally, the study assessed the public school nurses' perceived benefits of and barriers to helping students obtain public health insurance. A paper-and pencil survey was sent to a national random sample of 750 public school nurses. The response rate was 56%. RESULTS: Nearly 60% of respondents had helped students enroll in public health insurance. The majority perceived that helping students obtain public health insurance would reduce school absenteeism (90%), improve attention during school (84%), reduce the number of students held back (80%), reduce school dropouts (72%), and increase academic test scores (69%). Although the majority (53%) of nurses thought schools should assist students' parents with filling out public health insurance enrollment forms, some expressed reservations about the process. CONCLUSION: School nurses indicated health insurance is important for the health and academic success of students. These beliefs are congruent with state Child Health Insurance Program (CHIP) directors' perceptions, yet few schools have taken on the role of facilitating student enrollment in public health insurance programs. PMID- 20573146 TI - Community-acquired pneumonia in children: what's old? What's new? AB - Community-acquired pneumonia (CAP) still remains a significant cause for childhood morbidity worldwide. Streptococcus pneumoniae is the most important causative agent at all ages. Respiratory syncytial virus is common in young children, and Mycoplasma pneumoniae in schoolchildren. Paediatric CAP is universally treated with antibiotics; amoxicillin is the drug of choice for presumably pneumococcal and a macrolide for presumably atypical bacterial cases. Because of globally increased resistances, macrolides are not safety for pneumococcal CAP. At present, available prospective research data on the epidemiology of paediatric CAP in western countries are from 1970s to 1980s; correspondingly, data on bacterial aetiology are mainly from 1980s to 1990s. Current concepts on pneumococcal aetiology are mostly based on poorly validated antibody assays. Most data on clinical characteristics in children's CAP, as well as on antibiotic treatment come from developing countries, thus not being directly applicable in western communities. Recent viral studies have revealed the role of rhinoviruses, metapneumovirus and bocavirus in the aetiology of paediatric CAP. This review critically summarizes the available data on epidemiology, aetiology, clinical presentation, treatment and outcome of CAP in children, with special focus on the newest microbial findings, the age and applicability of the data and the need of new studies. PMID- 20573147 TI - Great auricular nerve blockade using high resolution ultrasound: a volunteer study. AB - This prospective, observational volunteer study aimed to describe the appearance of the great auricular nerve using ultrasound and its blockade under ultrasound guidance. An in-plane needle guidance technique was used for blockade of the great auricular nerve with 0.1 ml mepivacaine 1%. Sensory block was evaluated by pinprick testing in comparison with the contralateral area propriae. The great auricular nerve was successfully seen in all volunteers and the tail of the helix, antitragus, lobula and mandibular angle were blocked in all cases whereas the antihelix and concha were never blocked. Ultrasound imaging of the great auricular nerve can be reliably achieved and successful blockade with minimal volumes of local anaesthetic is another example of the benefits of ultrasound guided peripheral nerve blocks. PMID- 20573148 TI - The effect of pilot balloon design on estimation of safe tracheal tube cuff pressure. AB - We studied the effect of pilot balloon design on the ability of experienced anaesthetists to assess and inflate tracheal tube cuffs to safe pressures. A model trachea was designed, incorporating a degree of compliance and an air leak, to evaluate six different pilot balloons grafted onto identical tracheal tubes. Pilot balloons were inflated to one of four pressures and anaesthetists were asked to estimate whether the pressure was acceptable, too low or too high. Anaesthetists were then asked to inflate the cuff of each tube. Overall, 103 (42.9%) of anaesthetists' assessments of tracheal tube cuff pressures were correct (33% correct would be expected by chance, p = 0.002). Pressures generated by anaesthetists inflating tracheal tube cuffs were very variable. Median (IQR [range]) pressures for each pilot balloon ranged from 29 (17-43 [9-56]) cmH(2)O to 74 (49-114 [4-140]) cmH(2)O (p < 0.001). The design of the pilot balloon significantly affects anaesthetists' ability to inflate tracheal tube cuffs to safe pressures. PMID- 20573149 TI - The unrecognised difficult extubation: a call for vigilance. AB - Tracheal extubation remains a critical and often overlooked period of difficult airway management. A 66-year-old man, scheduled for C5-C7 anterior fusion, with an easy view of the vocal cords, presented with a sublaryngeal obstruction that required a reduced tracheal tube size. Despite correct tube placement, intra operative ventilation remained difficult. At the end of surgery a pulsatile tracheal compression was fibreopticially observed above the carina. After discussion with the attending otolaryngologist, neuromuscular blockade was antagonised and the patient was able to maintain normal minute volumes while spontaneously ventilating. With the otolaryngologist present, and with the patient conscious, the trachea was successfully extubated over an airway exchange catheter. A subsequent CT scan revealed an impingement of the trachea by the innominate artery and a mildly ectatic ascending and descending aorta that, in conjunction with tracheomalacia and neuromuscular blockade, could explain the observed signs and symptoms. PMID- 20573150 TI - Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial. AB - OBJECTIVE: Decreasing the prevalence of severe postpartum haemorrhages (PPH) is a major obstetrical challenge. These are often considered to be associated with substandard initial care. Strategies to increase the appropriateness of early management of PPH must be assessed. We tested the hypothesis that a multifaceted intervention aimed at increasing the translation into practice of a protocol for early management of PPH, would reduce the incidence of severe PPH. DESIGN: Cluster-randomised trial. POPULATION: 106 maternity units in six French regions. METHODS: Maternity units were randomly assigned to receive the intervention, or to have the protocol passively disseminated. The intervention combined outreach visits to discuss the protocol in each local context, reminders, and peer reviews of severe incidents, and was implemented in each maternity hospital by a team pairing an obstetrician and a midwife. MAIN OUTCOME MEASURES: The primary outcome was the incidence of severe PPH, defined as a composite of one or more of: transfusion, embolisation, surgical procedure, transfer to intensive care, peripartum haemoglobin decrease of 4 g/dl or more, death. The main secondary outcomes were PPH management practices. RESULTS: The mean rate of severe PPH was 1.64% (SD 0.80) in the intervention units and 1.65% (SD 0.96) in control units; difference not significant. Some elements of PPH management were applied more frequently in intervention units-help from senior staff (P = 0.005), or tended to - second-line pharmacological treatment (P = 0.06), timely blood test (P = 0.09). CONCLUSION: This educational intervention did not affect the rate of severe PPH as compared with control units, although it improved some practices. PMID- 20573151 TI - Acupuncture for the induction of labour: a double-blind randomised controlled study. AB - OBJECTIVE: To investigate whether acupuncture is effective for the induction of labour in post-term pregnancies. DESIGN: A double-blind multicentre randomised controlled study. SETTINGS: Aarhus University Hospital and Herning Regional Hospital, Denmark. POPULATION: One hundred and twenty-five healthy women with uneventful pregnancies at gestational week 41(+6) were randomised into two groups. METHODS: The intervention group was given acupuncture twice on the same day at acupuncture point GV20 and bilaterally at points BL67, LI4 and SP6. The control group received sham acupuncture at the same points. MAIN OUTCOME MEASURES: At effect evaluation, which was carried out 24 hours after randomisation, the primary endpoint was labour or delivery. RESULTS: The primary endpoint was achieved in seven women (12%) in the acupuncture group and eight women (14%) in the control group (P = 0.79). Stratification for parity and fetal gender did not alter the results. CONCLUSION: Under the treatment regimen investigated in this study, acupuncture for the induction of labour in post-term women at gestational age 41(+6) weeks may not be effective. PMID- 20573152 TI - Recurrence risk of stillbirth in a second pregnancy. AB - OBJECTIVE: To examine the risk of recurrence of stillbirth in a second pregnancy. DESIGN: Retrospective cohort study. SETTING: Scotland, UK. POPULATION: All women who delivered their first and second pregnancies in Scotland between 1981 and 2005. METHODS: All women delivering for the first time between 1981 and 2000 were linked to records of their second pregnancy using routinely collected data from the Scottish Morbidity Returns. Women who had an intrauterine death in their first pregnancy formed the exposed cohort, whereas those who had a live birth formed the unexposed cohort. MAIN OUTCOME MEASURE: Stillbirth in a second pregnancy. RESULTS: After adjusting for confounding factors, the odds of recurrence of stillbirth in a second pregnancy were found to be 1.94 (99% CI 1.29 2.92) compared with women who had had a live birth in their first pregnancy. Other factors associated with recurrence of stillbirth in a second pregnancy included placental abruption (adjusted OR 1.96; 99% CI 1.60-2.41), preterm delivery (adjusted OR 7.45; 99% CI 5.91-9.39) and low birthweight (adjusted OR 6.69; 99% CI 5.31-8.42). A Bayesian analysis using minimally informative normal priors found the risk of recurrence of stillbirth in a second pregnancy to be 1.59 (99% CI 1.10-2.33). CONCLUSIONS: Women who have stillbirth in their first pregnancy have a higher risk of recurrence in their next pregnancy. PMID- 20573153 TI - Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence-based approaches. AB - Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors in severe haemophilia A patients. Thirty years experience has shown high success rates (60-80%) with heterogeneous dose regimens and has led to the identification of clinical features that define the patients' prognostic profile. Children with recently diagnosed inhibitors are the best candidates for ITI and adequate management may further contribute to improve the short- and long-term ITI outcome. In these patients inhibitor eradication represents a cost-effective option because it enables the restoration of FVIII prophylaxis and consequently prevents arthropathy development. Adults with long standing inhibitors often show bad predictors of ITI outcome, however, ITI may be considered as a suitable and cost-effective approach in cases with frequent bleeds that are not satisfactorily controlled by by-passing treatment and/or when orthopaedic surgery is needed. Optimal ITI regimens should be established in these different settings and randomized trials are addressing these issues. This article reviews the available literature evidence and clinical implications with current recommendations on ITI management, and highlights the issues still unsolved. PMID- 20573154 TI - Prognostic factors in adult acute lymphoblastic leukaemia. AB - Treatment of acute lymphoblastic leukaemia (ALL) in adults presents a formidable challenge. While overall results have improved over the past 3 decades, the long term survival for patients aged less than 60 years is only in the range of 30-40% and is 10-15% if between 60 and 70 years and <5% for those over 70 years. The historic lack of clear-cut biological prognostic factors has led to over- or under-treatment of some patients. Response to initial therapy is an important prognosticator of outcome based on disease biology, as well as pharmacogenetics, which include the patient's response to drugs given. The more widespread availability of allogeneic transplantation and reduced-intensity regimens for older patients have opened up this curative modality to a greater number of patients. Hopefully, those options, as well as novel cytogenetic and molecular markers, will enable a better selection of patients who undergo intensive therapies and finally break the 30-40% cure barrier for adults with ALL. PMID- 20573155 TI - IkappaB kinase beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. AB - BACKGROUND: Nuclear factor (NF)-kappaB is a transcription factor that regulates cytokine and chemokine production in various inflammatory diseases, including bronchial asthma. IkappaB kinase (IKK) beta is important for NF-kappaB activation in inflammatory conditions, and is possibly related to airway remodelling. Thus, inhibition of the IKKbeta-NF-kappaB pathway may be an ideal strategy for the management of airway remodelling. OBJECTIVE: We examined the effects of a newly synthesized IKKbeta inhibitor, IMD-0354, in a chronic allergen exposure model of bronchial asthma in mice. METHODS: A chronic mouse model was generated by challenge with house dust mite antigen (Dermatophagoides pteronyssinus). IMD-0354 was administrated intraperitoneally in therapeutic groups. Lung histopathology, hyperresponsiveness and the concentrations of mediators and molecules in supernatants of lung homogenates were determined. RESULTS: NF-kappaB activation was inhibited by prolonged periods of IMD-0354 administration. IMD-0354 reduced the numbers of bronchial eosinophils. IMD-0354 also inhibited the pathological features of airway remodelling, including goblet cell hyperplasia, subepithelial fibrosis, collagen deposition and smooth muscle hypertrophy. Inhibition of these structural changes by IMD-0354 was the result of the suppressing the production and activation of remodelling-related mediators, such as TGF-beta, via inhibition of IKKbeta. IMD-0354 inhibited IL-13 and IL-1beta production, and it restored the production of IFN-gamma. It also ameliorated airway hyperresponsiveness. CONCLUSION: IKKbeta plays crucial roles in airway inflammation and remodelling in a chronic mouse model of asthma. A specific IKKbeta inhibitor, IMD-0354, may be therapeutically beneficial for treating airway inflammation and remodelling in chronic asthma. PMID- 20573157 TI - High glucose induces apoptosis in AC16 human cardiomyocytes via macrophage migration inhibitory factor and c-Jun N-terminal kinase. AB - 1. It is known that high glucose can induce cardiomyocyte apoptosis and that macrophage migration inhibitory factor (MIF) may be involved in the development of diabetes. However, the relationship between high glucose and MIF in diabetic cardiomyopathy remains unclear. 2. In the present study, AC16 human cardiomyocytes were cultured in the presence of 25 mmol/L glucose for 20, 30 and 60 min before being subjected to western blot analyses to determine MIF expression and c-Jun N-terminal kinase (JNK) activation. In addition, AC16 cells were pretreated with 2.5 MUmol/L SP600125 (a JNK inhibitor), 40 MUmol/L (s,r)-3 (4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1; an MIF antagonist) or 0.1% dimethylsulphoxide (DMSO; vehicle) for 1 h prior to exposure to 25 mmol/L glucose and culture for 72 h, followed by annexin V-fluorescein isothiocyanate/propidium iodide staining and flow cytometry analysis. Caspase 3 activity and phosphorylation of JNK were also analysed by western blotting. 3. The high concentration of glucose increased expression of endogenous MIF and JNK phosphorylation in AC16 cardiomyocytes. Pretreatment of cells with SP600125 and ISO-1 reduced glucose-induced apoptosis and caspase 3 activity. Furthermore, JNK phosphorylation was attenuated by inhibition of endogenous MIF. 4. In conclusion, myocardial cell apoptosis induced by high glucose involves the overexpression of MIF and activation of the JNK signalling pathway. The identification of a high glucose-MIF-JNK pathway will help determine potential new targets in the treatment of diabetic cardiomyopathy. PMID- 20573156 TI - Anti-Asthma Simplified Herbal Medicine Intervention-induced long-lasting tolerance to allergen exposure in an asthma model is interferon-gamma, but not transforming growth factor-beta dependent. AB - BACKGROUND: Chronic allergic asthma is the result of a T-helper type 2 (Th2) biased immune status. Current asthma therapies control symptoms in some patients, but a long-lasting therapy has not been established. Anti-Asthma Simplified Herbal Medicine Intervention (ASHMITM), a Chinese herbal formula, improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. OBJECTIVE: We evaluated the persistence of ASHMITM beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects. Methods BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper-reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMITM (OVA/ASHMITM) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post-therapy. In other experiments, OVA mice received ASHMITM treatment with concomitant neutralization of IFN-gamma or TGF-beta. Effects on airway responses, cytokine- and OVA-specific IgE levels were determined 8 weeks post-therapy. RESULTS: Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMITM and did not re-occur following OVA re-challenge up to 8 weeks post-therapy. Decreased allergen specific IgE and Th2 cytokine levels, and increased IFN-gamma levels also persisted at least 8 weeks post-therapy. ASHMITM effects were eliminated by the neutralization of IFN-gamma, but not TGF-beta, during therapy. CONCLUSION: ASHMITM induced long-lasting post-therapy tolerance to antigen-induced inflammation and AHR. IFN-gamma is a critical factor in ASHMITM effects. PMID- 20573159 TI - Potential amelioration of morbidity in patients with chromosomal anomalies: relevance to Bardet-Biedl syndrome. AB - Given the genetic basis of their disease, children with major chromosomal abnormalities including Bardet-Biedl syndrome (BBS) are generally considered to have a guarded prognosis with persistence or progression of disease manifestations. Although various therapeutic interventions are commonly used to control signs and symptoms of illness, parents of BBS children are usually cautioned against hoping for sustained improvement. A case of a 21-month-old girl, diagnosed with BBS, manifesting signs of worsening visual impairment, obesity, irascible and disordered behaviour, as well as developmental delay, is presented. After initial evaluation suggested specific biochemical deficiencies, nutritional status correction was undertaken and the patient's signs and symptoms subsequently resolved over the course of several months. To the authors' knowledge, this is the first case report of sustained resolution of all disease manifestations in the face of previously deteriorating health in a young child with this major chromosomal abnormality. It appears that biochemical imbalances and insufficiencies resulting from abnormal metabolism and excretion are potentially amenable to extraordinary dietary supplementation, with partial or complete resolution of clinical abnormalities. It is recommended that all children with chromosomal abnormalities have biochemical and nutritional status evaluation with correction of disordered biochemistry as is possible. PMID- 20573158 TI - Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. AB - Recessive inactivating mutations in the ABCC8 and KCNJ11 genes encoding the adenosine triphosphate-sensitive potassium (K(ATP)) channel subunit sulphonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel subunit (Kir6.2) are the most common cause of hyperinsulinaemic hypoglycaemia (HH). Most of these patients do not respond to treatment with the (K(ATP)) channel agonist diazoxide. Dominant inactivating ABCC8 and KCNJ11 mutations are less frequent, but are usually associated with a milder form of hypoglycaemia that is responsive to diazoxide therapy. We studied five patients from four families with HH who were unresponsive to diazoxide and required a near total pancreatectomy. Mutations in KCNJ11 and ABCC8 were sought by sequencing and dosage analysis. Three novel heterozygous ABCC8 mis-sense mutations (G1485E, D1506E and M1514K) were identified in four probands. All the mutations affect residues located within the Nucleotide Binding Domain 2 of the SUR1 subunit. Testing of family members showed that the mutations had arisen de novo with dominant inheritance in one pedigree. This study extends the clinical phenotype associated with dominant (K(ATP)) channel mutations to include severe congenital HH requiring near total pancreatectomy in addition to a milder form of diazoxide responsive hypoglycaemia. The identification of dominant vs recessive mutations does not predict clinical course but it is important for estimating the risk of HH in future siblings and offspring. PMID- 20573160 TI - Haplotype sharing test maps genes for familial cardiomyopathies. AB - Identifying a mutation in a heterogeneous disease such as inherited cardiomyopathy is a challenge because classical methods, like linkage analysis, can often not be applied as there are too few meioses between affected individuals. However, if affected individuals share the same causal mutation, they will also share a genomic region surrounding it. High-density genotyping arrays are able to identify such regions shared among affected individuals. We hypothesize that the longest shared haplotype is most likely to contain the disease-causing mutation. We applied this method to two pedigrees: one with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one with dilated cardiomyopathy (DCM), using high-density genome-wide SNP arrays. In the ARVC pedigree, the largest haplotype was on chromosome 12 and contained a causative PKP2 mutation. In the DCM pedigree, a causative MYH7 mutation was present on a large shared haplotype on chromosome 14. We calculated that a pedigree containing at least seven meioses has a high chance of correctly detecting the mutation containing haplotype as the largest. Our data show that haplotype sharing analysis can assist in identifying causative genes in families with low penetrance Mendelian diseases, in which standard tools cannot be used due to lack of sufficient pedigree information. PMID- 20573161 TI - Autism severity is associated with child and maternal MAOA genotypes. AB - Autism severity is associated with child and maternal MAOA genotypes. We replicated and extended a previously reported association between autism severity and a functional polymorphism in the monoamine oxidase A (MAOA) promoter region, MAOA-uVNTR, in a sample of 119 males, aged 2-13 years, with autism spectrum disorder from simplex families. We demonstrated that (i) boys with the low activity 3-repeat MAOA allele had more severe sensory behaviors, arousal regulation problems, and aggression, and worse social communication skills than males with the high activity allele; and (ii) problems with aggression, as well as with fears and rituals, were modified by the mothers' genotype. Boys with the 4-repeat high activity allele who had homozygous 4-repeat mothers showed increased severity of these behaviors relative to those born to heterozygous mothers. These findings indicate the importance of considering maternal genotype in examining associations of MAOA and other genes with behavior in male offspring. PMID- 20573162 TI - YSPSL (rPSGL-Ig) for improvement of early renal allograft function: a double blind, placebo-controlled, multi-center Phase IIa study. AB - INTRODUCTION: Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models. PATIENTS AND METHODS: This randomized 15-center, double-blind, 59 patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated. RESULTS: No drug-specific toxicities or increased adverse event rates were noted. Two YSPSL-treated patients died of causes determined as unrelated to study drug. YSPSL did not reduce the incidence of dialysis within the first week post-transplant (41% in treated vs. 20% in placebo patients). Renal function endpoints scored at post operative days 1 & 2 were also not impacted by YSPSL. However, at day 5, the fraction of patients with serum creatinine above 6 mg/dL was lower in the YSPSL vs. placebo group (26% vs. 55%, p = 0.043). Large variations in the dialysis delayed graft function (DGF) rates were observed between centers, independently of treatment assignment, indicating subjectivity of this endpoint. CONCLUSION: In this first Ph2a study in kidney transplantation, YSPSL was safe but did not impact the dialysis-DGF rate. Further studies with more objective efficacy endpoints are required to define the impact of YSPSL on early renal allograft function. PMID- 20573163 TI - Formaldehyde-releasers: relationship to formaldehyde contact allergy. Part 2: Metalworking fluids and remainder. AB - We have reviewed formaldehyde-releasers used in metalworking fluids (MWFs) in this and a previous part of a two-part article. These biocides do not appear to be frequent or important sensitizers. Even in highly selected patient groups of metalworkers, mean prevalence rates of sensitivity are low: 0.2% for Tris(hydroxymethyl)nitromethane, 1.6% for tris(N-hydroxyethyl)hexahydrotriazine, 1.9% for Bioban P-1487 and Bioban CS-1246, and 2.8% for Bioban CS-1135. In the case of the Biobans, many reactions may have been irritant. Only N,N' methylenebis(5-methyloxazolidine) has a fairly high mean score of 4.0% in metalworkers. With the exception of Bioban P-1487, there is a clear relationship between positive patch test reactions to the releasers and formaldehyde sensitivity: 40-70% of reactions to releasers occur in patients sensitive to formaldehyde and may therefore be caused by formaldehyde allergy. There is a lack of reliable data on the clinical relevance of contact allergy to the formaldehyde releasers in MWF. In most studies, no data on relevance were provided and in those that did, relevance was often found for a (very small) minority of the reactions only. Also discussed here are the formaldehyde-releasers MDM hydantoin, methenamine, N-methylolchloracetamide, paraformaldehyde, and Preventol D2. PMID- 20573164 TI - Relationship between formaldehyde and quaternium-15 contact allergy. Influence of strength of patch test reactions. AB - BACKGROUND: In groups of patients with formaldehyde allergy, many have positive patch tests to quaternium-15. Conversely, of patients allergic to quaternium-15, over half also react to formaldehyde. OBJECTIVES: To test our hypothesis that patients with stronger patch test reactions to formaldehyde are more likely to react to quaternium-15, attesting to the aetiological role for formaldehyde in such co-reactivity. METHODS: Retrospective analysis of all patients patch tested with formaldehyde and quaternium-15 in the European baseline series between 1994 and 2009 (TRUE test). RESULTS: In a group of 86 patients allergic to formaldehyde, 73% co-reacted to quaternium-15; in the subgroup of 70 women, the percentage was 83. In both groups, more reactions were observed to quaternium-15 in the patients with a ++ reaction compared to the patients with a + reaction to formaldehyde. Conversely, stronger reactions to quaternium-15 were significantly more often associated with formaldehyde sensitivity in a group of 107 patients reacting to quaternium-15 and a subgroup of 88 women. In men, such effects were not observed and only 5 of 16 (31%) men allergic to formaldehyde also reacted to quaternium-15. CONCLUSIONS: In women, but not in men, stronger reactions to formaldehyde lead to more positive quaternium-15 patch tests. PMID- 20573165 TI - A spot test for detection of cobalt release - early experience and findings. AB - BACKGROUND: It is often difficult to establish clinical relevance of metal exposure in cobalt-allergic patients. Dermatologists and patients may incorrectly assume that many metallic items release cobalt at levels that may cause cobalt dermatitis. Cobalt-allergic patients may be unaware that they are exposed to cobalt from handling work items, causing hand dermatitis. OBJECTIVES: To present early findings with a newly developed cobalt spot test. METHODS AND RESULTS: A cobalt spot test based on disodium-1-nitroso-2-naphthol-3,6-disulfonate was able to identify cobalt release at 8.3 ppm. The test may also be used as a gel test if combined with an agar preparation. We found no false-positive reactions when testing metals and alloys known not to contain cobalt. However, one cobalt containing alloy, which elicited cobalt dermatitis in cobalt-allergic patients, was negative upon cobalt gel testing. CONCLUSIONS: The cobalt test detects amounts of cobalt release that approximate the elicitation concentration seen in cobalt-allergic patients. It may serve as a useful tool in dermatology offices and workplaces. PMID- 20573166 TI - Fragrance contact allergy: a 4-year retrospective study. AB - BACKGROUND: Fragrance chemicals are the second most frequent cause of contact allergy. The mandatory labelling of 26 fragrance chemicals when present in cosmetics has facilitated management of patients allergic to fragrances. OBJECTIVES: The study was aimed to define the characteristics of the population allergic to perfumes detected in our hospital district, to determine the usefulness of markers of fragrance allergy in the baseline GEIDAC series, and to describe the contribution made by the fragrance series to the data obtained with the baseline series. MATERIAL AND METHODS: We performed a 4-year retrospective study of patients tested with the Spanish baseline series and/or fragrance series. There are four fragrance markers in the baseline series: fragrance mix I (FM I), Myroxylon pereirae, fragrance mix II (FM II), and hydroxyisohexyl 3 cyclohexene carboxaldehyde. RESULTS: A total of 1253 patients were patch tested, 117 (9.3%) of whom were positive to a fragrance marker. FM I and M. pereirae detected 92.5% of the cases of fragrance contact allergy. FM II and hydroxyisohexyl 3-cyclohexene carboxaldehyde detected 6 additional cases and provided further information in 8, enabling improved management. A fragrance series was tested in a selected group of 86 patients and positive results were obtained in 45.3%. Geraniol was the allergen most frequently found in the group of patients tested with the fragrance series. CONCLUSIONS: Classic markers detect the majority of cases of fragrance contact allergy. We recommend incorporating FM II in the Spanish baseline series, as in the European baseline series, and using a specific fragrance series to study patients allergic to a fragrance marker. PMID- 20573167 TI - Formaldehyde-releasers: relationship to formaldehyde contact allergy. Metalworking fluids and remainder. Part 1. AB - This is part of a series of review articles on formaldehyde-releasers and their relationship to formaldehyde contact allergy. Formaldehyde-releasers used in metalworking fluids (MWF) and a group of releasers not presented in previous articles are discussed. Here, in Part 1 of the article, there is a short overview of the composition and functions of MWF, the function of biocides in them, and adverse reactions to MWF. In addition, the releasers in MWF that have caused contact allergy are presented with CAS, synonyms, molecular formula, chemical structure, applications, patch test studies, and amount of formaldehyde released by them. In Part 2 of the article, the relationship between formaldehyde releasers used in MWF and formaldehyde contact allergy is discussed as are data on miscellaneous releasers not previously presented, followed by a discussion of Parts 1 and 2 of the article. PMID- 20573168 TI - Photoallergic contact dermatitis from benzydamine presenting mainly as lip dermatitis. AB - BACKGROUND: Benzydamine, a non-steroidal anti-inflammatory drug (NSAID) in use for more than four decades, has been reported to cause photosensitivity. OBJECTIVES: To study the results of photopatch testing to benzydamine and the clinical features of the dermatitis during a 3-year period (2006-2008). PATIENTS AND METHODS: During this period, 74 patients with photodermatoses were photopatch tested with an extended baseline series of allergens including benzydamine and in suspicious cases, with drugs that contain it. Test sites were irradiated on D2 with 5 J/cm(2) and readings were performed on D2 and D4. RESULTS: Ten patients (six females/four males), aged 21-84 years (mean 64.9) had a positive photopatch test to benzydamine [1-5% petrolatum (pet.) from Bial-Aristegui] and to drugs that contain it (Tantum verde oral solution and Momen gel). Nine patients had lower lip cheilitis and one lichenified eczema on photo-exposed sites. CONCLUSION: Photosensitivity from both topical and systemic benzydamine has been occasionally described, mainly in southern Spain. Despite its widespread use and its known photosensitizing capacity, photoallergic contact dermatitis from benzydamine is probably underdiagnosed as the clinical presentation of mainly the lip and chin is not typical of photoallergic contact dermatitis and benzydamine is not part of most photoallergen series. PMID- 20573169 TI - Reduce suture complications by applying proper knot tying techniques. PMID- 20573170 TI - Use of a preliminary horizontal mattress suture on scalp biopsies to achieve rapid hemostasis. PMID- 20573171 TI - Novel bolstering technique for full-thickness skin grafts on the ear. PMID- 20573172 TI - Intermediate-thickness skin grafting for repair of cutaneous defects after Mohs micrographic surgery. PMID- 20573173 TI - Value of the extended field of view modality in the sonographic imaging of cutaneous melanoma: a pictorial essay. PMID- 20573174 TI - Phenol chemical matricectomy is less painful, with shorter recovery times but higher recurrence rates, than surgical matricectomy: a patient's view. AB - BACKGROUND: Ingrown toenails have a tendency for recurrence. Operative interventions can be successful, and several procedures are in use. OBJECTIVE: Retrospective evaluation, to reveal differences in postoperative pain, time to recovery, and satisfaction with the cosmetic outcome in patients treated with a phenol (PCM) or surgical matricectomy (SM). MATERIALS & METHODS: All matricectomy patients at the Dermatology Department of the Ludwigshafen City Hospital between 2004 and 2008 were interviewed over the telephone. Of 72 evaluable patients with a total of 112 ingrown nail sides, 33 were treated with PCM and 39 with SM. The patient group consisted of 40.3% women, the median age was 31. RESULTS: Patients after PCM indicated two points less postoperative pain on an analogue scale from 0 to 10 (p<.001). In the PCM group, more patients recovered from the operation in less than 1 week (p=.007). Patient evaluation of cosmetic outcome was not different between the groups (p=.76), but recurrence rates were significantly higher in the PCM group (31.5%, vs 6.9% in the SM group, p=.006) CONCLUSION: Both matricectomies have advantages and disadvantages. We should discuss these issues with our patients to help them decide on the kind of matricectomy. PMID- 20573175 TI - Partial excision of matrix and phenolic ablation for the treatment of ingrowing toenail: a 36-month follow-up of 197 treated patients. AB - BACKGROUND: Several options for the treatment of ingrowing toenails are available, ranging from simple conservative approaches to extensive surgical procedures. OBJECTIVE: To evaluate in a long-term follow-up (36 months) the efficacy of chemical matricectomy with phenol for the treatment of ingrowing toenails. METHODS AND MATERIALS: A total of 197 phenol ablations were performed in 139 patients with stage 2 and 3 disease. Each patient was examined weekly until full wound healing was achieved and was followed for 36 months to assess the long-term efficacy of the treatment. The healing period after surgery ranged from 2 to 4 weeks; few postoperative complications were seen. RESULTS: Only three recurrences were observed (after 2, 4, and 11 months). Short-term results were excellent. No severe complications occurred during the 36-month follow-up period. Cosmetic results were remarkable. The success rate was 98.5%. CONCLUSIONS: Phenol cauterization is an excellent surgical method for the treatment of ingrowing toenails, being simple and associated with low morbidity and a high success rate, even over the long term (36 months). PMID- 20573176 TI - Treatment of acne scars using subdermal minimal surgery technology. AB - BACKGROUND: Acne is a common condition, seen in up to 80% of people aged 11 to 30. In some patients, it can result in permanent scars that are surprisingly difficult to treat, with current treatments for acne scars having limited efficacy. Recently, subdermal minimal surgery technology has been introduced as a novel therapeutic modality for acne scars. OBJECTIVE: To evaluate the clinical efficacy and safety of subdermal minimal surgery technology for treating acne scars. MATERIALS AND METHODS: Ten Korean patients (Fitzpatrick skin type II-V) with acne scars were enrolled in this study. They received three sessions of subdermal minimal surgery technology at 4-week intervals. The treatment parameters were a one-shot 0.15-mL volume of hyaluronic acid (HA) and 70% pressure power with a 10- x 10-mm square-shaped tip. Two independent dermatologists evaluated clinical improvement using a quartile grading scale by comparing digital photographs taken before treatment (baseline) and 3 months after the last treatment. The patients also evaluated any side effects at each visit. At the end of the study, the patients documented pain severity (none, mild, moderate, or severe) during the procedure and degree of satisfaction (worse, no change, mild, moderate, or strong improvement). RESULTS: All volunteers completed the three treatment sessions and were satisfied with the procedure. Three months after the last treatment session, according to the physicians' assessments, two patients had improvement of greater than 75% in acne scars, six had 50% to 75% improvement, and two had 25% to 50% improvement. Patient degree of satisfaction was similar to the physicians' assessment. There were no side effects except transient spot bleeding at entry points and slight edema that resolved within 48 hours. CONCLUSION: Subdermal minimal surgery technology is an effective and safe method for improving acne scars. PMID- 20573177 TI - Maternal uniparental isodisomy is responsible for serious molybdenum cofactor deficiency. AB - Molybdenum cofactor (MoCo) deficiency is a rare autosomal recessive inherited metabolic disorder resulting in the combined deficiency of aldehyde oxidase, xanthine dehydrogenase, and sulfite oxidase. We report a male infant with MoCo deficiency whose clinical findings consisted of microcephaly, intractable seizures soon after birth, feeding difficulties, and developmental delay. Sequencing of MOCS1, MOCS2, and GEPH genes, and single nucleotide polymorphism genotyping array analysis showed, to our knowledge, unusual inheritance of MoCo deficiency/maternal uniparental isodisomy for the first time in the literature. At 10 months of age, he now has microcephaly and developmental delay, and his seizures are controlled with phenobarbital, clonozepam, and vigabatrin therapy. PMID- 20573178 TI - Cerebral sinus venous thrombosis in Swiss children. AB - AIMo describe the characteristics of paediatric cerebral sinus venous thrombosis (CSVT) in Switzerland. METHOD: data on clinical features, neuroimaging, risk factors, and treatment were collected for all children in Switzerland younger than 16 years of age who had CSVT between January 2000 and December 2008. A follow-up examination and a cognitive assessment were performed (mean follow-up period 26mo). Differences between neonates and children (patients older than 28d) were assessed and predictors of outcome were determined. RESULTS: twenty-one neonates (14 males, seven females; mean age 9d, SD 8d) and 44 children (30 males, 14 females; mean age 8y 7mo, SD 4y 5mo) were reported. The incidence of paediatric CSVT in Switzerland was 0.558 per 100000 per year. In neonates, the deep venous system was more often involved and parenchymal injuries were more common. The strongest predictor of poor outcome was neonatal age (odds ratio 17.8, 95% confidence interval 0.847-372.353). Most children showed global cognitive abilities within the normal range, but impairments in single cognitive subdomains were frequent. INTERPRETATION: paediatric CSVT is rare. Its outcome is poor in neonates. Most children have good neurological outcomes, but some patients have individual neuropsychological impairments. PMID- 20573179 TI - Survival with Rett syndrome: comparing Rett's original sample with data from the Australian Rett Syndrome Database. AB - AIM: rett syndrome is a severe neurodevelopmental disorder that typically affects females. Little is known about the natural history and survival time of these females. METHOD: we compared the survival of all Austrian female participants from Rett's historical cohort (1966) with that of affected females registered in the Australian Rett Syndrome Database. The analysis included both Kaplan-Meier analysis and a log-rank test for equality of survivor functions. RESULTS: of females in the original Austrian group, three are still alive. The median age at death was 13 years 4.8 months. The probability of survival up to the age of 25 years was 21%, compared with 71% in the Australian cohort (p<0.001). We found no practical or statistically significant differences in survival between the various birth year groups within the Australian cohort. INTERPRETATION: our data indicate that survival of females with Rett syndrome has improved since the late 1960s but that there has been shown no change in survival over the last 30 years, possibly because the follow-up time has been too short. PMID- 20573180 TI - Decreased fracture incidence after 1 year of pamidronate treatment in children with spastic quadriplegic cerebral palsy. AB - AIM: The aim of this study was to assess the rate of fracture before and after a 1-year course of intravenous pamidronate in children with spastic quadriplegic cerebral palsy (CP) who had previously experienced fractures. METHOD: Twenty-five children (nine males, 16 females) with quadriplegic CP in Gross Motor Function Classification System (GMFCS) level IV or V who were treated with intravenous pamidronate for approximately 1 year were identified. All participants had previously experienced at least one non-traumatic fracture. Each received 15 doses of pamidronate over a mean of 13.6 months. Post-treatment observation ranged from 1 to 10 years 6 months (mean 4 y 1 mo). The fracture rate before and after commencement of treatment was calculated using the person-years method. RESULTS: The participants had experienced a total of 86 fractures before treatment began, occurring over 280.6 person-years, giving a fracture rate of 30.6% per year. During the post-treatment observation period, totalling 107.5 person-years, 8 of the 25 children experienced a total of 14 fractures. This fracture rate of 13.0% per year is a statistically significant decrease (p=0.02). INTERPRETATION: Pamidronate treatment lowered the rate of fracture, and a 1-year course appears to provide a protective effect after treatment ends. For the majority of participants, this effect lasted 4 years or longer. However, a subset of children suffered a fracture soon after the drug was discontinued. In these children, a longer course of treatment appears to have been necessary. PMID- 20573184 TI - The nasty neighbour in the striped mouse (Rhabdomys pumilio) steals paternity and elicits aggression. AB - BACKGROUND: Territoriality functions to monopolize access to resources including mates, but is costly in terms of energy and time investment. Some species reduce these costs by being less aggressive towards their neighbours than towards unfamiliar strangers, the so called dear enemy phenomenon. However, in other species individuals are more, not less aggressive towards their neighbours. It has been hypothesised that this is due to the fact that neighbours can impose a greater threat than strangers, but this has not been tested previously. RESULTS: We tested aggression in wild group-living male striped mice in a neutral test arena and demonstrate that breeders are more aggressive than non-breeding philopatrics, and that more aggression occurs during the breeding than during the non-breeding season. Male breeders were significantly more aggressive towards their neighbours than towards strangers, leading to the prediction that neighbours are the most important competitors for paternity. Using a molecular parentage analysis we show that 28% of offspring are sired by neighbouring males and only 7% by strangers. CONCLUSIONS: We conclude that in male striped mice the main function of male aggression is defending paternity against their territorial neighbours. PMID- 20573183 TI - Mechanical anchorage and peri-implant bone formation of surface-modified zirconia in minipigs. AB - AIM: To test the hypothesis that peri-implant bone formation and mechanical stability of surface-modified zirconia and titanium implants are equivalent. MATERIALS AND METHODS: Twelve minipigs received three types of implants on either side of the mandible 8 weeks after removal of all pre-molar teeth: (i) a zirconia implant with a sandblasted surface; (ii) a zirconia implants with a sandblasted and etched surface; and (iii) a titanium implant with a sandblasted and acid etched surface that served as a control. Removal torque and peri-implant bone regeneration were evaluated in six animals each after 4 and 13 weeks. RESULTS: The titanium surface was significantly rougher than both tested zirconia surfaces. Mean bone to implant contact (BIC) did not differ significantly between the three implant types after 4 weeks but was significantly higher for titanium compared with both zirconia implants after 13 weeks (p<0.05). Bone volume density (BVD) did not differ significantly at any interval. Removal torque was significantly higher for titanium compared with both zirconia surfaces after 4 and 13 weeks (p<0.001). The sandblasted and etched zirconia surface showed a significantly higher removal torque after 4 weeks compared with sandblasted zirconia (p<0.05); this difference levelled out after 13 weeks. CONCLUSIONS: It is concluded that all implants achieved osseointegration with similar degrees of BIC and BVD; however, titanium implants showed a higher resistance to removal torque, probably due to higher surface roughness. PMID- 20573181 TI - Progressive accumulation of amyloid-beta oligomers in Alzheimer's disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins. AB - The cognitive impairment in patients with Alzheimer's disease is closely associated with synaptic loss in the neocortex and limbic system. Although the neurotoxic effects of aggregated amyloid-beta oligomers in Alzheimer's disease have been studied extensively in experimental models, less is known about the characteristics of these aggregates across the spectrum of Alzheimer's disease. In this study, postmortem frontal cortex samples from controls and patients with Alzheimer's disease were fractionated and analyzed for levels of oligomers and synaptic proteins. We found that the levels of oligomers correlated with the severity of cognitive impairment (blessed information-memory-concentration score and mini-mental state examination) and with the loss of synaptic markers. Reduced levels of the synaptic vesicle protein, vesicle-associated membrane protein-2, and the postsynaptic protein, postsynaptic density-95, correlated with the levels of oligomers in the various fractions analyzed. The strongest associations were found with amyloid-beta dimers and pentamers. Co-immunoprecipitation and double labeling experiments supported the possibility that amyloid-beta and postsynaptic density-95 interact at synaptic sites. Similarly, in transgenic mice expressing high levels of neuronal amyloid precursor protein, amyloid-beta co immunoprecipitated with postsynaptic density-95. This was accompanied by a decrease in the levels of the postsynaptic proteins Shank1 and Shank3 in patients with Alzheimer's disease and in the brains of amyloid precursor protein transgenic mice. In conclusion, this study suggests that the presence of a subpopulation of amyloid-beta oligomers in the brains of patients with Alzheimer's disease might be related to alterations in selected synaptic proteins and cognitive impairment. PMID- 20573185 TI - Adverse drug reactions from psychotropic medicines in the paediatric population: analysis of reports to the Danish Medicines Agency over a decade. AB - BACKGROUND: The prescribing of psychotropic medicines for the paediatric population is rapidly increasing. In attempts to curb the use of psychotropic medicine in the paediatric population, regulatory authorities have issued various warnings about risks associated with use of these products in childhood. Little evidence has been reported about the adverse drug reactions (ADRs) of these medicines in practice. As spontaneous reports are the main source for information about previously unknown ADRs, we analysed data submitted to a national ADR database. The objective was to characterise ADRs reported for psychotropic medicines in the Danish paediatric population over a decade. FINDINGS: All spontaneous ADR reports from 1998 to 2007 for children from birth to 17 years of age were included. The unit of analysis was one ADR. We analysed the distribution of ADRs per year, seriousness, age and gender of the child, suspected medicine and type of reported ADR. A total of 429 ADRs were reported for psychotropic medicines and 56% of these were classified as serious. Almost 20% of psychotropic ADRs were reported for children from birth up to 2 years of age and one half of ADRs were reported in adolescents, especially for antidepressants and psychostimulants. Approximately 60% of ADRs were reported for boys. Forty percent of all ADRs were from the category 'nervous and psychiatric disorders'. All but one ADR reported for children below two years were serious and two of these were fatal. A number of serious ADRs reported in children from birth up to 2 years of age were presumably caused by mothers' use of psychotropic medicines during pregnancy. CONCLUSION: The high number of serious ADRs reported for psychotropic medicines in the paediatric population should be a concern for health care professionals and physicians. Considering the higher number of birth defects being reported greater care has to be given while prescribing these drugs for pregnant women. PMID- 20573186 TI - An excess vessel in the posterior part of the human cerebral arterial circle (CAC): a case series. AB - BACKGROUND: As a continuation of the previous findings in human fetuses, accidental finding of an accessory vascular component in the posterior part of CAC of human adult cadavers inspired the authors to present and compare its posterior part configuration. CASE PRESENTATION: Examination was carried out on brains of 48 human adult cadavers, routinely dissected at the Institute of Forensic Medicine. The aberrant vessel in the posterior part of four CACs was discovered.Vascular components of the posterior segment of CAC or of the whole CAC were described and photographed. A comparison between fetal and adult cases was also presented. CONCLUSIONS: Based on the fact that the age of the four presented cases ranged from 73 to 84 and based on the causes of their death, we concluded that the angioarchitecture of the posterior part of the CAC is a consequence of the embryonic or primitive arterial stabilization and interaction with normal adult vessels. PMID- 20573188 TI - The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection. AB - BACKGROUND: Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection. RESULTS: The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance. CONCLUSIONS: Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule. PMID- 20573187 TI - The efficacy and safety of insulin-sensitizing drugs in HIV-associated lipodystrophy syndrome: a meta-analysis of randomized trials. AB - BACKGROUND: HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. METHODS: We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each outcome. RESULTS: Sixteen trials involving 920 patients met inclusion criteria. Rosiglitazone modestly improved fasting insulin (WMD -3.67 mU/L; CI -7.03, -0.31) but worsened triglycerides (WMD 32.5 mg/dL; CI 1.93, 63.1), LDL (WMD 11.33 mg/dL; CI 1.85, 20.82) and HDL (WMD -2.91 mg/dL; CI -4.56, -1.26) when compared to placebo or no treatment in seven trials. Conversely, pioglitazone had no impact on fasting insulin, triglycerides or LDL but improved HDL (WMD 7.60 mg/dL; CI 0.20, 15.0) when compared to placebo in two trials. Neither drug favorably impacted measures of fat redistribution. Based on six trials with placebo or no treatment controls, metformin reduced fasting insulin (WMD -8.94 mU/L; CI -13.0, -4.90), triglycerides (WMD -42.87 mg/dL; CI -73.3, -12.5), body mass index (WMD -0.70 kg/m2; CI -1.09, -0.31) and waist-to-hip ratio (WMD -0.02; CI -0.03, 0.00). Three trials directly compared metformin to rosiglitazone. While effects on insulin were comparable, lipid levels and measures of fat redistribution all favored metformin. Severe adverse events were uncommon in all 16 trials. CONCLUSION: Based on our meta-analysis, rosiglitazone should not be used in HALS. While pioglitazone may be safer, any benefits appear small. Metformin was the only insulin-sensitizer to demonstrate beneficial effects on all three components of HALS. PMID- 20573189 TI - Dichotomization: 2 x 2 (x2 x 2 x 2...) categories: infinite possibilities. AB - BACKGROUND: Consumers of epidemiology may prefer to have one measure of risk arising from analysis of a 2-by-2 table. However, reporting a single measure of association, such as one odds ratio (OR) and 95% confidence interval, from a continuous exposure variable that was dichotomized withholds much potentially useful information. Results of this type of analysis are often reported for one such dichotomization, as if no other cutoffs were investigated or even possible. METHODS: This analysis demonstrates the effect of using different theory and data driven cutoffs on the relationship between body mass index and high cholesterol using National Health and Nutrition Examination Survey data. The recommended analytic approach, presentation of a graph of ORs for a range of cutoffs, is the focus of most of the results and discussion. RESULTS: These cutoff variations resulted in ORs between 1.1 and 1.9. This allows investigators to select a result that either strongly supports or provides negligible support for an association; a choice that is invisible to readers. The OR curve presents readers with more information about the exposure disease relationship than a single OR and 95% confidence interval. CONCLUSION: As well as offering results for additional cutoffs that may be of interest to readers, the OR curve provides an indication of whether the study focuses on a reasonable representation of the data or outlier results. It offers more information about trends in the association as the cutoff changes and the implications of random fluctuations than a single OR and 95% confidence interval. PMID- 20573190 TI - Role of type 1 and type 3 fimbriae in Klebsiella pneumoniae biofilm formation. AB - BACKGROUND: Klebsiella pneumoniae is an important gram-negative opportunistic pathogen causing primarily urinary tract infections, respiratory infections, and bacteraemia. The ability of bacteria to form biofilms on medical devices, e.g. catheters, has a major role in development of many nosocomial infections. Most clinical K. pneumoniae isolates express two types of fimbrial adhesins, type 1 fimbriae and type 3 fimbriae. In this study, we characterized the role of type 1 and type 3 fimbriae in K. pneumoniae biofilm formation. RESULTS: Isogenic fimbriae mutants of the clinical K. pneumoniae isolate C3091 were constructed, and their ability to form biofilm was investigated in a flow cell system by confocal scanning laser microscopy. The wild type strain was found to form characteristic biofilm and development of K. pneumoniae biofilm occurred primarily by clonal growth, not by recruitment of planktonic cells. Type 1 fimbriae did not influence biofilm formation and the expression of type 1 fimbriae was found to be down-regulated in biofilm forming cells. In contrast, expression of type 3 fimbriae was found to strongly promote biofilm formation. CONCLUSION: By use of well defined isogenic mutants we found that type 3 fimbriae, but not type 1 fimbriae, strongly promote biofilm formation in K. pneumoniae C3091. As the vast majority of clinical K. pneumoniae isolates express type 3 fimbriae, this fimbrial adhesin may play a significant role in development of catheter associated K. pneumoniae infections. PMID- 20573192 TI - Recent trends in exposure to secondhand smoke in the United States population. AB - BACKGROUND: Previous research using the National Health and Nutrition Examination Surveys (NHANES) data documented a significant downward trend in secondhand smoke (SHS) exposure between 1988 and 2002. The objective of this study was to assess whether the downward trend in exposure continued from 2001 through 2006. METHODS: We analyzed data from the 2001-2006 NHANES to estimate exposure of nonsmokers to SHS. Geometric means of serum cotinine levels for all nonsmokers were computed. RESULTS: Overall serum cotinine levels (95% Confidence Intervals) in 2001-2002, 2003-2004, and 2005-2006 were 0.06 ng/mL (0.05-0.07), 0.07 ng/mL (0.06-0.09), and 0.05 ng/mL (0.05-0.06), respectively. Subgroup analysis by age, gender, and race/ethnicity groups showed similar trends in cotinine levels. Children, males, and non-Hispanic Blacks had higher cotinine levels than adults, females, and non Hispanic Whites and Mexican Americans, respectively. Insignificant P values from the Wald test indicate that serum cotinine levels did not differ over time. CONCLUSIONS: The long-term trend of declining exposure to SHS among nonsmokers appears to have leveled off. However, disparities noted in previous research persist today, with the young, non-Hispanic Blacks, and males experiencing higher levels of exposure. PMID- 20573191 TI - Crosstalks between integrin alpha 5 and IGF2/IGFBP2 signalling trigger human bone marrow-derived mesenchymal stromal osteogenic differentiation. AB - BACKGROUND: The potential of mesenchymal stromal cells (MSCs) to differentiate into functional bone forming cells provides an important tool for bone regeneration. The identification of factors that trigger osteoblast differentiation in MSCs is therefore critical to promote the osteogenic potential of human MSCs. In this study, we used microarray analysis to identify signalling molecules that promote osteogenic differentiation in human bone marrow stroma derived MSCs. RESULTS: Microarray analysis and validation experiments showed that the expression of IGF2 and IGFBP2 was increased together with integrin alpha5 (ITGA5) during dexamethasone-induced osteoblast differentiation in human MSCs. This effect was functional since we found that IGF2 and IGFBP2 enhanced the expression of osteoblast phenotypic markers and in vitro osteogenic capacity of hMSCs. Interestingly, we showed that downregulation of endogenous ITGA5 using specific shRNA decreased IGF2 and IGFBP2 expression in hMSCs. Conversely, ITGA5 overexpression upregulated IGF2 and IGFBP2 expression in hMSCs, which indicates tight crosstalks between these molecules. Consistent with this concept, activation of endogenous ITGA5 using a specific antibody that primes the integrin, or a peptide that specifically activates ITGA5 increased IGF2 and IGFBP2 expression in hMSCs. Finally, we showed that pharmacological inhibition of FAK/ERK1/2-MAPKs or PI3K signalling pathways that are enhanced by ITGA5 activation, blunted IGF2 and IGFBP2 expression in hMSCs. CONCLUSION: The results show that ITGA5 is a key mediator of IGF2 and IGFBP2 expression that promotes osteoblast differentiation in human MSCs, and reveal that crosstalks between ITGA5 and IGF2/IGFBP2 signalling are important mechanisms that trigger osteogenic differentiation in human bone marrow derived mesenchymal stromal cells. PMID- 20573193 TI - Absence of functional TolC protein causes increased stress response gene expression in Sinorhizobium meliloti. AB - BACKGROUND: The TolC protein from Sinorhizobium meliloti has previously been demonstrated to be required for establishing successful biological nitrogen fixation symbiosis with Medicago sativa. It is also needed in protein and exopolysaccharide secretion and for protection against osmotic and oxidative stresses. Here, the transcriptional profile of free-living S. meliloti 1021 tolC mutant is described as a step toward understanding its role in the physiology of the cell. RESULTS: Comparison of tolC mutant and wild-type strains transcriptomes showed 1177 genes with significantly increased expression while 325 had significantly decreased expression levels. The genes with an increased expression suggest the activation of a cytoplasmic and extracytoplasmic stress responses possibly mediated by the sigma factor RpoH1 and protein homologues of the CpxRA two-component regulatory system of Enterobacteria, respectively. Stress conditions are probably caused by perturbation of the cell envelope. Consistent with gene expression data, biochemical analysis indicates that the tolC mutant suffers from oxidative stress. This is illustrated by the elevated enzyme activity levels detected for catalase, superoxide dismutase and glutathione reductase. The observed increase in the expression of genes encoding products involved in central metabolism and transporters for nutrient uptake suggests a higher metabolic rate of the tolC mutant. We also demonstrated increased swarming motility in the tolC mutant strain. Absence of functional TolC caused decreased expression mainly of genes encoding products involved in nitrogen metabolism and transport. CONCLUSION: This work shows how a mutation in the outer membrane protein TolC, common to many bacterial transport systems, affects expression of a large number of genes that act in concert to restore cell homeostasis. This finding further underlines the fundamental role of this protein in Sinorhizobium meliloti biology. PMID- 20573194 TI - Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance. AB - BACKGROUND: Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance conferring Plasmodium falciparum mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS. MATERIALS AND METHODS: Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance. RESULTS: Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of dhfr 51I, 108N, and 59R and dhps 437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the dhfr 164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the dhfr and dhps genes identified only one additional polymorphism, dhps 581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children. CONCLUSION: Despite high prevalence of known anti folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of dhfr 164L mutation. PMID- 20573195 TI - The Drosophila Anion Exchanger (DAE) lacks a detectable interaction with the spectrin cytoskeleton. AB - BACKGROUND: Current models suggest that the spectrin cytoskeleton stabilizes interacting ion transport proteins at the plasma membrane. The human erythrocyte anion exchanger (AE1) was the first membrane transport protein found to be associated with the spectrin cytoskeleton. Here we evaluated a conserved anion exchanger from Drosophila (DAE) as a marker for studies of the downstream effects of spectrin cytoskeleton mutations. RESULTS: Sequence comparisons established that DAE belongs to the SLC4A1-3 subfamily of anion exchangers that includes human AE1. Striking sequence conservation was observed in the C-terminal membrane transport domain and parts of the N-terminal cytoplasmic domain, but not in the proposed ankyrin-binding site. Using an antibody raised against DAE and a recombinant transgene expressed in Drosophila S2 cells DAE was shown to be a 136 kd plasma membrane protein. A major site of expression was found in the stomach acid-secreting region of the larval midgut. DAE codistributed with an infolded subcompartment of the basal plasma membrane of interstitial cells. However, spectrin did not codistribute with DAE at this site or in anterior midgut cells that abundantly expressed both spectrin and DAE. Ubiquitous knockdown of DAE with dsRNA eliminated antibody staining and was lethal, indicating that DAE is an essential gene product in Drosophila. CONCLUSIONS: Based on the lack of colocalization and the lack of sequence conservation at the ankyrin-binding site, it appears that the well-characterized interaction between AE1 and the spectrin cytoskeleton in erythrocytes is not conserved in Drosophila. The results establish a pattern in which most of the known interactions between the spectrin cytoskeleton and the plasma membrane in mammals do not appear to be conserved in Drosophila. PMID- 20573196 TI - Global transcriptional response to carbonic anhydrase IX deficiency in the mouse stomach. AB - BACKGROUND: Carbonic anhydrases (CAs) are a family of enzymes that regulate pH homeostasis in various tissues. CA IX is an exceptional member of this family because in addition to the basic CA function, it has been implicated in several other physiological and pathological processes. Functions suggested for CA IX include roles in cell adhesion and malignant cell invasion. In addition, CA IX likely regulates cell proliferation and differentiation, which was demonstrated in Car9-/- mice. These mice had gastric pit cell hyperplasia and depletion of chief cells; however, the specific molecular mechanisms behind the observed phenotypes remain unknown. Therefore, we wanted to study the effect of CA IX deficiency on whole-genome gene expression in gastric mucosa. This was done using Illumina SentrixMouse-6 Expression BeadChip arrays. The expression of several genes with notable fold change values was confirmed by QRT-PCR. RESULTS: CA IX deficiency caused the induction of 86 genes and repression of 46 genes in the gastric mucosa. There was 92.9% concordance between the results obtained by microarray analysis and QRT-PCR. The differentially expressed genes included those involved in developmental processes and cell differentiation. In addition, CA IX deficiency altered the expression of genes responsible for immune responses and downregulated the expression of several digestive enzymes. CONCLUSIONS: Microarray analysis identified several potential genes whose altered expression could explain the disturbed cell lineage phenotype in the Car9-/- gastric mucosa. The results also indicated a novel role for CA IX in the regulation of immunologic processes and digestion. These findings reinforce the concept that the main role of CA IX is not the regulation of pH in the stomach mucosa. Instead, it is needed for proper function of several physiological processes. PMID- 20573197 TI - Inverse folding of RNA pseudoknot structures. AB - BACKGROUND: RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. RESULTS: In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. CONCLUSIONS: The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions. PMID- 20573198 TI - Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. AB - BACKGROUND: HIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial. RESULTS: Here, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI. CONCLUSIONS: Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy. PMID- 20573199 TI - Plasmodium vivax circumsporozoite genotypes: a limited variation or new subspecies with major biological consequences? AB - BACKGROUND: Plasmodium vivax circumsporozoite variants have been identified in several geographical areas. The real implication of the genetic variation in this region of the P. vivax genome has been questioned for a long time. Although previous studies have observed significant association between VK210 and the Duffy blood group, we present here that evidences of this variation are limited to the CSP central portion. METHODS: The phylogenetic analyses were accomplished starting from the amplification of conserved domains of 18 SSU RNAr and Cyt B. The antibodies responses against the CSP peptides, MSP-1, AMA-1 and DBP were detected by ELISA, in plasma samples of individuals infected with two P. vivax CS genotypes: VK210 and P. vivax-like. RESULTS: These analyses of the two markers demonstrate high similarity among the P. vivax CS genotypes and surprisingly showed diversity equal to zero between VK210 and P. vivax-like, positioning these CS genotypes in the same clade. A high frequency IgG antibody against the N- and C-terminal regions of the P. vivax CSP was found as compared to the immune response to the R- and V- repetitive regions (p = 0.0005, Fisher's Exact test). This difference was more pronounced when the P. vivax-like variant was present in the infection (p = 0.003, Fisher's Exact test). A high frequency of antibody response against MSP-1 and AMA-1 peptides was observed for all P. vivax CS genotypes in comparison to the same frequency for DBP. CONCLUSIONS: This results target that the differences among the P. vivax CS variants are restrict to the central repeated region of the protein, mostly nucleotide variation with important serological consequences. PMID- 20573201 TI - Sitting and standing performance in a total population of children with cerebral palsy: a cross-sectional study. AB - BACKGROUND: Knowledge of sitting and standing performance in a total population of children with cerebral palsy (CP) is of interest for health care planning and for prediction of future ability in the individual child. In 1994, a register and a health care programme for children with CP in southern Sweden was initiated. In the programme information on how the child usually sits, stands, stands up and sits down, together with use of support or assistive devices, is recorded annually. METHODS: A cross-sectional study was performed, analysing the most recent report of all children with CP born 1990-2005 and living in southern Sweden during 2008. All 562 children (326 boys, 236 girls) aged 3-18 years were included in the study. The degree of independence, use of support or assistive devices to sit, stand, stand up and sit down was analysed in relation to the Gross Motor Function Classification System (GMFCS), CP subtype and age. RESULT: A majority of the children used standard chairs (57%), could stand independently (62%) and could stand up (62%) and sit down (63%) without external support. Adaptive seating was used by 42%, external support to stand was used by 31%, to stand up by 19%, and to sit down by 18%. The use of adaptive seating and assistive devices increased with GMFCS levels (p < 0.001) and there was a difference between CP subtypes (p < 0.001). The use of support was more frequent in preschool children aged 3-6 (p < 0.001). CONCLUSION: About 60% of children with CP, aged 3-18, use standard chairs, stand, stand up, and sit down without external support. Adding those using adaptive seating and external support, 99% of the children could sit, 96% could stand and 81% could stand up from a sitting position and 81% could sit down from a standing position. The GMFCS classification system is a good predictor of sitting and standing performance. PMID- 20573200 TI - Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training. AB - BACKGROUND: Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the gluteus medius at two time points: T(1) - untrained, (9 +/- 0.5 months old) and T(2) - trained (20 +/- 0.7 months old). RESULTS: The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes ACADVL, MRPS21 and SLC25A29 encoded by the nuclear genome. Among the 58 genes with decreased expression, MSTN, a negative regulator of muscle growth, had the greatest decrease.Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (P < 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton. CONCLUSION: Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure. PMID- 20573202 TI - Varicella susceptibility and transmission dynamics in Slovenia. AB - BACKGROUND: A cross-sectional, age-stratified study was conducted to determine varicella-zoster seroprevalence and force of infection in Slovenia. METHODS: 3689 serum samples were tested for VZV IgG antibodies with an enzyme immunoassay. Semiparametric and parametric modelling were used to estimate the force of infection. RESULTS: Overall, 85.6% of serum samples were seropositive. Age specific prevalence rose rapidly in preschool children and over 90% of 8 years old tested positive for VZV. However, 2.8% of serum samples among women of childbearing age were seronegative. Semiparametric modelling yielded force of infection estimates of 0.182 (95% CI 0.158-0.206), 0.367 (95% CI 0.285-0.448) and 0.008 (95% CI 0.0-0.032) for age groups 0.5- < 6, 6-11 and >or=12 years, respectively, and 0.175 (95% CI 0.147-0.202), 0.391 (95% CI 0.303-0.480) and 0.025 (95% CI 0.003-0.046) for age groups 0.5- < 5, 5-9 and >or=10 years, respectively. CONCLUSIONS: Regardless of the age grouping used, the highest transmission occurred in children in their first years of school. PMID- 20573203 TI - Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study. AB - INTRODUCTION: A large number of patients resuscitated for primary cardiac arrest arrive in the intensive care unit (ICU) with a body temperature < 35.0 degrees C. The aim of this observational cohort study was to determine the association between ICU admission temperature and neurological outcome in this patient group. METHODS: Demographics and parameters influencing neurological outcome were retrieved from the charts of all patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia in our ICU from January 2006 until January 2008. Patients were divided into two groups according to their body temperature on ICU admission: a hypothermia group (< 35.0 degrees C) and a non hypothermia group (>or=35.0 degrees C). Neurological outcome after six months was assessed by means of the Glasgow Outcome Score (GOS), with GOS 1 to 3 defined as unfavorable and GOS 4 to 5 as favorable. A logistic regression model was used to analyze the influence of the different parameters on neurological outcome. RESULTS: The data of 105 consecutive patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia were analyzed. Median ICU admission temperature was 35.1 degrees C (interquartile range (IQR) 34.3 to 35.7). After six months, 61% of the patients had an unfavorable outcome (59% died and 2% were severely disabled), whereas 39% had a favorable outcome (moderate disability or good recovery). Among patients with spontaneous hypothermia on ICU admission, the percentage with unfavorable outcome was higher (69% versus 50%, P = 0.05). Logistic regression showed that age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores and spontaneous hypothermia on ICU admission all had an increased odds ratio (OR) for an unfavorable outcome after six months. Spontaneous hypothermia had the strongest association with unfavorable outcome (OR 2.6, 95% CI (confidence interval) 1.1 to 5.9), which became even stronger after adjustment for age, presenting heart rhythm, APACHE II and SOFA scores (OR 3.8, CI 1.3 to 11.0). CONCLUSIONS: In this observational cohort study, spontaneous hypothermia on ICU admission was the strongest predictor of an unfavorable neurological outcome in patients resuscitated for primary cardiac arrest. PMID- 20573204 TI - Effect of high intratesticular estrogen on global gene expression and testicular cell number in rats. AB - BACKGROUND: The identification of estrogen receptors alpha and beta and aromatase in the testis has highlighted the important role of estrogens in regulating spermatogenesis. There is a wealth of information on the deleterious effects of fetal and neonatal exposure of estrogens and xenoestrogens in the testis, including spermiation failure and germ cell apoptosis. However, very little is known about gene transcripts affected by exogenous estradiol exposure in the testis. The objective of the present study was to unveil global gene expression profiles and testicular cell number changes in rats after estradiol treatment. METHODS: 17beta-estradiol was administered to adult male rats at a dose of 100 micrograms/kg body weight in saline daily for 10 days; male rats receiving only saline were used as controls. Microarray analysis was performed to examine global gene expression profiles with or without estradiol treatment. Real time RT-PCR was conducted to verify the microarray data. In silico promoter and estrogen responsive elements (EREs) analysis was carried out for the differentially expressed genes in response to estradiol. Quantitation of testicular cell number based on ploidy was also performed using flow cytometry in rats with or without estradiol treatment. RESULTS: We found that 221 genes and expressed sequence tags (ESTs) were differentially expressed in rat testes treated with estradiol compared to the control; the microarray data were confirmed by real time RT-PCR. Gene Ontology analysis revealed that a number of the differentially expressed genes are involved in androgen and xenobiotic metabolism, maintenance of cell cytoskeleton, endocytosis, and germ cell apoptosis. A total of 33 up-regulated genes and 67 down-regulated genes showed the presence of EREs. Flow cytometry showed that estradiol induced a significant decrease in 2n cells (somatic and germ cells) and 4n cells (pachytene spermatocytes) and a marked increase in the number of elongated and elongating spermatids. CONCLUSIONS: This study provides a novel insight into the molecular basis for spermiation failure and apoptosis caused by 17beta-estradiol and it also offers new mechanisms by which adult exposure to environmental estrogens can affect spermatogenesis and fertility. PMID- 20573205 TI - Anti-inflammatory effect of bee pollen ethanol extract from Cistus sp. of Spanish on carrageenan-induced rat hind paw edema. AB - BACKGROUND: Bee pollen, a honeybee product, is the feed for honeybees prepared themselves by pollens collecting from plants and has been consumed as a perfect food in Europe, because it is nutritionally well balanced. In this study, we aimed to investigate the anti-inflammatory effect of bee pollen from Cistus sp. of Spanish origin by a method of carrageenan-induced paw edema in rats, and to investigate the mechanism of anti-inflammatory action and also to elucidate components involved in bee pollen extracted with ethanol. METHODS: The bee pollen bulk, its water extract and its ethanol extract were administered orally to rats. One hour later, paw edema was produced by injecting of 1% solution of carrageenan, and paw volume was measured before and after carrageenan injection up to 5 h. The ethanol extract and water extract were measured COX-1 and COX-2 inhibitory activities using COX inhibitor screening assay kit, and were compared for the inhibition of NO production in LPS-stimulated RAW 264.7 cells. The constituents of bee pollen were purified from the ethanol extract subjected to silica gel or LH-20 column chromatography. Each column chromatography fractions were further purified by repeated ODS or silica gel column chromatography. RESULTS: The bee pollen bulk mildly suppressed the carrageenan-induced paw edema and the water extract showed almost no inhibitory activity, but the ethanol extract showed relatively strong inhibition of paw edema. The ethanol extract inhibited the NO production and COX-2 but not COX-1 activity, but the water extract did not affect the NO production or COX activities. Flavonoids were isolated and purified from the ethanol extract of bee pollen, and identified at least five flavonoids and their glycosides. CONCLUSIONS: It is suggested that the ethanol extract of bee pollen show a potent anti-inflammatory activity and its effect acts via the inhibition of NO production, besides the inhibitory activity of COX-2. Some flavonoids included in bee pollen may partly participate in some of the anti-inflammatory action. The bee pollen would be beneficial not only as a dietary supplement but also as a functional food. PMID- 20573206 TI - Ectopic primary type A thymoma located in two thoracic vertebras: a case report. AB - BACKGROUND: The thymus arises in the ventral portion of the third and fourth pharyngeal pouch. It descends into the anterior mediastinum at 6th week of gestation. Any errors occurring during this process can cause dissemination of aberrant nodules that are responsible for most atypical thymomas. CASE PRESENTATION: The authors report a unusual case of type-A thymoma located in D10 and D11 vertebral bodies.The histology showed a uniform growth of short, spindle shaped, mitotically inactive cells. A few small, normal lymphocytes were seen scattered or in small groups. The immunohistochemical investigation for neuroectodermal, neuroendocrine, vascular and muscular markers were negative. It also confirmed the presence of CD3+, CD5+ T lymphocytes and the absence of immature T-lymphocyte markers. CONCLUSIONS: The case described shows a thymic hystogenesis for spindle cell tumours. To our knowledge no other cases of vertebral thymomas have been described in international literature. PMID- 20573207 TI - Associations between partial sickness benefit and disability pensions: initial findings of a Finnish nationwide register study. AB - BACKGROUND: Timely return to work after longterm sickness absence and the increased use of flexible work arrangements together with partial health-related benefits are tools intended to increase participation in work life. Although partial sickness benefit and partial disability pension are used in many countries, prospective studies on their use are largely lacking. Partial sickness benefit was introduced in Finland in 2007. This register study aimed to investigate the use of health-related benefits by subjects with prolonged sickness absence, initially on either partial or full sick leave. METHODS: Representative population data (13 375 men and 16 052 women either on partial or full sick leave in 2007) were drawn from national registers and followed over an average of 18 months. The registers provided information on the study outcomes: diagnoses and days of payment for compensated sick leaves, and the occurrence of disability pension. Survival analysis and multinomial regression were carried out using sociodemographic variables and prior sickness absence as covariates. RESULTS: Approximately 60% of subjects on partial sick leave and 30% of those on full sick leave had at least one recurrent sick leave over the follow up. A larger proportion of those on partial sick leave (16%) compared to those on full sick leave (1%) had their first recurrent sick leave during the first month of follow up. The adjusted risks of the first recurrent sick leave were 1.8 and 1.7 for men and women, respectively, when subjects on partial sick leave were compared with those on full sick leave. There was no increased risk when those with their first recurrent sick leave in the first month were excluded from the analyses. The risks of a full disability pension were smaller and risks of a partial disability pension approximately two-fold among men and women initially on partial sick leave, compared to subjects on full sick leave. CONCLUSIONS: This is the first follow up study of the newly adopted partial sickness benefit in Finland. The results show that compared to full sick leave, partial sick leave - when not followed by lasting return to work - is more typically followed by partial disability pension and less frequently by full disability pension. It is anticipated that the use of partial benefits in connection with part-time participation in work life will have favourable effects on future disability pension rates in Finland. PMID- 20573208 TI - Subnormal vitamin B12 concentrations and anaemia in older people: a systematic review. AB - BACKGROUND: Pernicious anaemia is undeniably associated with vitamin B12 deficiency, but the association between subnormal vitamin B12 concentrations and anaemia in older people is unclear. The aim of this systematic review was to evaluate the association between subnormal vitamin B12 concentrations and anaemia in older people. METHODS: Clinical queries for aetiology and treatment in bibliographic databases (PubMed [01/1949-10/2009]; EMBASE [01/1980-10/2009]) were used. Reference lists were checked for additional relevant studies. Observational studies (> or =50 participants) and randomized placebo-controlled intervention trials (RCTs) were considered. RESULTS: 25 studies met the inclusion criteria. Twenty-one observational cross-sectional studies (total number of participants n = 16185) showed inconsistent results. In one longitudinal observational study, low vitamin B12 concentrations were not associated with an increased risk of anaemia (total n = 423). The 3 RCTs (total n = 210) were well-designed and showed no effect of vitamin B12 supplementation on haemoglobin concentrations during follow-up in subjects with subnormal vitamin B12 concentrations at the start of the study. Due to large clinical and methodological heterogeneity, statistical pooling of data was not performed. CONCLUSIONS: Evidence of a positive association between a subnormal serum vitamin B12 concentration and anaemia in older people is limited and inconclusive. Further well-designed studies are needed to determine whether subnormal vitamin B12 is a risk factor for anaemia in older people. PMID- 20573209 TI - Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer. AB - BACKGROUND: The role of TNFalpha in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function. METHODS: This study used immunohistochemistry to investigate the expression of TNFalpha in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC. RESULTS: TNFalpha expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFalpha density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFalpha density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFalpha expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFalpha+ cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001). CONCLUSIONS: The expression of TNFalpha in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFalpha by macrophages and mast cells is critical for this relationship. PMID- 20573211 TI - Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India. AB - BACKGROUND: The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion. METHODS: A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, et al (1999). RESULTS: Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion. CONCLUSIONS: It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia. PMID- 20573210 TI - Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts. AB - BACKGROUND: Hemiascomycetous yeasts have intron-poor genomes with very few cases of alternative splicing. Most of the reported examples result from intron retention in Saccharomyces cerevisiae and some have been shown to be functionally significant. Here we used transcriptome-wide approaches to evaluate the mechanisms underlying the generation of alternative transcripts in Yarrowia lipolytica, a yeast highly divergent from S. cerevisiae. RESULTS: Experimental investigation of Y. lipolytica gene models identified several cases of alternative splicing, mostly generated by intron retention, principally affecting the first intron of the gene. The retention of introns almost invariably creates a premature termination codon, as a direct consequence of the structure of intron boundaries. An analysis of Y. lipolytica introns revealed that introns of multiples of three nucleotides in length, particularly those without stop codons, were underrepresented. In other organisms, premature termination codon-containing transcripts are targeted for degradation by the nonsense-mediated mRNA decay (NMD) machinery. In Y. lipolytica, homologs of S. cerevisiae UPF1 and UPF2 genes were identified, but not UPF3. The inactivation of Y. lipolytica UPF1 and UPF2 resulted in the accumulation of unspliced transcripts of a test set of genes. CONCLUSIONS: Y. lipolytica is the hemiascomycete with the most intron-rich genome sequenced to date, and it has several unusual genes with large introns or alternative transcription start sites, or introns in the 5' UTR. Our results suggest Y. lipolytica intron structure is subject to significant constraints, leading to the under-representation of stop-free introns. Consequently, intron containing transcripts are degraded by a functional NMD pathway. PMID- 20573212 TI - Deficiency in mouse Y chromosome long arm gene complement is associated with sperm DNA damage. AB - BACKGROUND: Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies are infertile in vivo and in vitro. We have previously shown that sperm from these males, although having grossly malformed heads, were able to fertilize oocytes via intracytoplasmic sperm injection (ICSI) and yield live offspring. However, in continuing ICSI trials we noted a reduced efficiency when cryopreserved sperm were used and with epididymal sperm as compared to testicular sperm. In the present study we tested if NPYq deficiency is associated with sperm DNA damage - a known cause of poor ICSI success. RESULTS: We observed that epididymal sperm from mice with severe NPYq deficiency (that is, deletion of nine tenths or the entire NPYq gene complement) are impaired in oocyte activation ability following ICSI and there is an increased incidence of oocyte arrest and paternal chromosome breaks. Comet assays revealed increased DNA damage in both epididymal and testicular sperm from these mice, with epididymal sperm more severely affected. In all mice the level of DNA damage was increased by freezing. Epididymal sperm from mice with severe NPYq deficiencies also suffered from impaired membrane integrity and abnormal chromatin condensation and suboptimal chromatin protamination. It is therefore likely that the increased DNA damage associated with NPYq deficiency is a consequence of disturbed chromatin remodeling. CONCLUSIONS: This study provides the first evidence of DNA damage in sperm from mice with NPYq deficiencies and indicates that NPYq-encoded gene/s may play a role in processes regulating chromatin remodeling and thus in maintaining DNA integrity in sperm. PMID- 20573213 TI - Alternative splicing is frequent during early embryonic development in mouse. AB - BACKGROUND: Alternative splicing is known to increase the complexity of mammalian transcriptomes since nearly all mammalian genes express multiple pre-mRNA isoforms. However, our knowledge of the extent and function of alternative splicing in early embryonic development is based mainly on a few isolated examples. High throughput technologies now allow us to study genome-wide alternative splicing during mouse development. RESULTS: A genome-wide analysis of alternative isoform expression in embryonic day 8.5, 9.5 and 11.5 mouse embryos and placenta was carried out using a splicing-sensitive exon microarray. We show that alternative splicing and isoform expression is frequent across developmental stages and tissues, and is comparable in frequency to the variation in whole transcript expression. The genes that are alternatively spliced across our samples are disproportionately involved in important developmental processes. Finally, we find that a number of RNA binding proteins, including putative splicing factors, are differentially expressed and spliced across our samples suggesting that such proteins may be involved in regulating tissue and temporal variation in isoform expression. Using an example of a well characterized splicing factor, Fox2, we demonstrate that changes in Fox2 expression levels can be used to predict changes in inclusion levels of alternative exons that are flanked by Fox2 binding sites. CONCLUSIONS: We propose that alternative splicing is an important developmental regulatory mechanism. We further propose that gene expression should routinely be monitored at both the whole transcript and the isoform level in developmental studies. PMID- 20573214 TI - The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle. AB - BACKGROUND: The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3. RESULTS: To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3. CONCLUSIONS: Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data. PMID- 20573215 TI - Missed opportunities for earlier HIV testing and diagnosis at the health facilities of Dessie town, North East Ethiopia. AB - BACKGROUND: For patients in all health-care settings HIV screening is recommended after the patient is notified that testing will be performed unless the patient declines. The nation's physicians and other health care providers should assume a much more active role in promoting HIV testing. The aim of this study was to investigate the extent to which missed opportunities for earlier HIV testing and diagnosis occur in the health facilities of north east Ethiopia. METHODS: A confidential client exit interview and medical record review was made on 427 clients who attended health facilities of Dessie town between November-December 2008. Data collection was done by counselors trained on Provider Initiated Counseling and Testing (PICT) and data collection tool included demographics, reason for visit to health facilities, HIV test initiation by service providers, clients self risk perception, clients willingness and acceptance of HIV test, HIV test result and review of client medical records. RESULTS: Among 427 clients, missed opportunities for HIV testing were found in 76.1% (325) of clients. HIV test initiation was made by data collecting counselors during interview period and 80.0% (260) of clients not initiated by service providers were found to be willing to have HIV test. Large number, 43.0% (112), of the willing clients actually tested for HIV. Of the tested clients, 13.4% (15) were found to be HIV positive. Most, 60% (9), of HIV positive clients who lost the opportunities of diagnosis felt themselves as having no risk for HIV infection. Missed opportunities for HIV diagnosis of 51.7% (15), overall HIV test acceptance rate of 36.5% (154) and positivity rate of 6.9% (29) were found. CONCLUSIONS: The missed opportunities for earlier HIV test and diagnosis of patients attending health facilities were found to be high and frequent. Testing only clients with HIV risk misses large number of HIV positive patients. Asking clients' willingness for HIV testing should be conducted by all service providers irrespective of the clients' risk behaviors for HIV infection or the type of services they need. PMID- 20573216 TI - High prevalence of plasmid-mediated 16S rRNA methylase gene rmtB among Escherichia coli clinical isolates from a Chinese teaching hospital. AB - BACKGROUND: Recently, production of 16S rRNA methylases by Gram-negative bacilli has emerged as a novel mechanism for high-level resistance to aminoglycosides by these organisms in a variety of geographic locations. Therefore, the spread of high-level aminoglycoside resistance determinants has become a great concern. METHODS: Between January 2006 and July 2008, 680 distinct Escherichia coli clinical isolates were collected from a teaching hospital in Wenzhou, China. PCR and DNA sequencing were used to identify 16S rRNA methylase and extended-spectrum beta-lactamase (ESBL) genes, including armA and rmtB, and in situ hybridization was performed to determine the location of 16S rRNA methylase genes. Conjugation experiments were subsequently performed to determine whether aminoglycoside resistance was transferable from the E. coli isolates via 16S rRNA methylase bearing plasmids. Homology of the isolates harboring 16S rRNA methylase genes was determined using pulse-field gel electrophoresis (PFGE). RESULTS: Among the 680 E. coli isolates, 357 (52.5%), 346 (50.9%) and 44 (6.5%) isolates were resistant to gentamicin, tobramycin and amikacin, respectively. Thirty-seven of 44 amikacin resistant isolates harbored 16S rRNA methylase genes, with 36 of 37 harboring the rmtB gene and only one harboring armA. The positive rates of 16S rRNA methylase genes among all isolates and amikacin-resistant isolates were 5.4% (37/680) and 84.1% (37/44), respectively. Thirty-one isolates harboring 16S rRNA methylase genes also produced ESBLs. In addition, high-level aminoglycoside resistance could be transferred by conjugation from four rmtB-positive donors. The plasmids of incompatibility groups IncF, IncK and IncN were detected in 34, 3 and 3 isolates, respectively. Upstream regions of the armA gene contained ISCR1 and tnpU, the latter a putative transposase gene,. Another putative transposase gene, tnpD, was located within a region downstream of armA. Moreover, a transposon, Tn3, was located upstream of the rmtB. Nineteen clonal patterns were obtained by PFGE, with type H representing the prevailing pattern. CONCLUSION: A high prevalence of plasmid-mediated rmtB gene was found among clinical E. coli isolates from a Chinese teaching hospital. Both horizontal gene transfer and clonal spread were responsible for the dissemination of the rmtB gene. PMID- 20573217 TI - BDNF Val66Met polymorphism, energy intake and BMI: a follow-up study in schoolchildren at risk of eating disorders. AB - BACKGROUND: Eating disorders (ED) have a multifactorial aetiology in which genetics play an important role. Several studies have found an association between the Val66Met (G196A) polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) and Eating disorders.The aim of this study was to determine the association of the Val66Met (G196A) polymorphism of the BDNF gene and its effect on eating disorders (ED), energy intake and BMI in schoolchildren. METHODS: Two year cohort study (preadolescence to adolescence). From an initial sample of 1336 Caucasian children (mean age = 11.37 years), a group at risk of ED (n = 141) and a control group (n = 117) were selected using the Children's Eating Attitudes Test. Two years later, they were re-classified into an at-risk group (n = 41) and a control group (n = 159) using the Eating Attitudes Test. The diagnosis of the individuals at risk of ED was confirmed by means of the Diagnostic Interview for Children and Adolescents. BMI, energy intake and the Val66Met (G196A) polymorphism of the BDNF gene were analysed in the at-risk and control groups. RESULTS: The frequency of genotypes of the Val66Met (G196A) polymorphism of the BDNF gene is 28.6% (95% CI: 22.4-34.9) in the heterozygous form (Val/Met) and 5% (95% CI: 2.4-9) in the homozygous form (Met/Met). We detected no association between Val66Met genotypes and the severity of ED. Over time, the carriers of the Met66 allele with a persistent risk of ED significantly restricted energy intake (507 Kcal/day; p = 0.033). CONCLUSION: We have not found an association between Val66Met (G196A) polymorphism of the BDNF and ED in schoolchildren from general population. The relationship found between this polymorphism and energy intake restriction in adolescents with a persistent risk of ED should be replicated in a larger sample. PMID- 20573218 TI - Can vaccinia virus be replaced by MVA virus for testing virucidal activity of chemical disinfectants? AB - BACKGROUND: Vaccinia virus strain Lister Elstree (VACV) is a test virus in the DVV/RKI guidelines as representative of the stable enveloped viruses. Since the potential risk of laboratory-acquired infections with VACV persists and since the adverse effects of vaccination with VACV are described, the replacement of VACV by the modified vaccinia Ankara strain (MVA) was studied by testing the activity of different chemical biocides in three German laboratories. METHODS: The inactivating properties of different chemical biocides (peracetic acid, aldehydes and alcohols) were tested in a quantitative suspension test according to the DVV/RKI guideline. All tests were performed with a protein load of 10% fetal calf serum with both viruses in parallel using different concentrations and contact times. Residual virus was determined by endpoint dilution method. RESULTS: The chemical biocides exhibited similar virucidal activity against VACV and MVA. In three cases intra-laboratory differences were determined between VACV and MVA - 40% (v/v) ethanol and 30% (v/v) isopropanol are more active against MVA, whereas MVA seems more stable than VACV when testing with 0.05% glutardialdehyde. Test accuracy across the three participating laboratories was high. Remarkably inter laboratory differences in the reduction factor were only observed in two cases. CONCLUSIONS: Our data provide valuable information for the replacement of VACV by MVA for testing chemical biocides and disinfectants. Because MVA does not replicate in humans this would eliminate the potential risk of inadvertent inoculation with vaccinia virus and disease in non-vaccinated laboratory workers. PMID- 20573219 TI - How is the balance between protein synthesis and degradation achieved? AB - Unlike most substances that cells manufacture, proteins are not produced and broken down by a common series of chemical reactions, but by completely different (independent and disconnected) mechanisms that possess no intrinsic means of making the rates of the two processes equal and attaining steady state concentrations. Balance between them is achieved extrinsically and is often imagined today to be the result of the actions of chemical feedback agents. But however instantiated, chemical feedback or any similar mechanism can only rectify induced imbalances in a system previously balanced by other means. Those "other means" necessarily involve reversible mass action or equilibrium-based interactions between native and altered forms of protein molecules somewhere in time and space between their synthesis and degradation. PMID- 20573220 TI - Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus. AB - BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. Genital involvement occurs when most other common sites are concurrently affected or are in remission. Systemic lupus erythematosus (SLE) is an autoimmune disease that may affect many parts of the body and the skin with occasional bullous lesions. Pemphigus vulgaris and SLE may be associated, albeit rarely. Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva. CASE PRESENTATION: A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva. Her history was characterized by systemic lupus erythematosus and PV. Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3. One month later a new biopsy revealed progression from VIN 3 to early SCC. Despite chemotherapy, no remission of disease was observed. She died six months after diagnosis CONCLUSION: Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC. It suggests the need for careful follow-up of patients with chronic inflammatory disease, especially when concomitant autoimmune disorders are present. Moreover, a biopsy should be always performed if there are PV lesions because of the possibility of neoplastic disease. PMID- 20573221 TI - Perceptions of newly admitted undergraduate medical students on experiential training on community placements and working in rural areas of Uganda. AB - BACKGROUND: Uganda has an acute problem of inadequate human resources partly due to health professionals' unwillingness to work in a rural environment. One strategy to address this problem is to arrange health professional training in rural environments through community placements. Makerere University College of Health Sciences changed training of medical students from the traditional curriculum to a problem-based learning (PBL) curriculum in 2003. This curriculum is based on the SPICES model (student-centered, problem-based, integrated, community-based and services oriented). During their first academic year, students undergo orientation on key areas of community-based education, after which they are sent in interdisciplinary teams for community placements. The objective was to assess first year students' perceptions on experiential training through community placements and factors that might influence their willingness to work in rural health facilities after completion of their training. METHODS: The survey was conducted among 107 newly admitted first year students on the medical, nursing, pharmacy and medical radiography program students, using in depth interview and open-ended self-administered questionnaires on their first day at the college, from October 28-30, 2008. Data was collected on socio demographic characteristics, motivation for choosing a medical career, prior exposure to rural health facilities, willingness to have part of their training in rural areas and factors that would influence the decision to work in rural areas. RESULTS: Over 75% completed their high school from urban areas. The majority had minimal exposure to rural health facilities, yet this is where most of them will eventually have to work. Over 75% of the newly admitted students were willing to have their training from a rural area. Perceived factors that might influence retention in rural areas include the local context of work environment, support from family and friends, availability of continuing professional training for career development and support of co-workers and the community. CONCLUSION: Many first year students at Makerere University have limited exposure to health facilities in rural areas and have concerns about eventually working there. PMID- 20573222 TI - Influence of muscle fitness test performance on metabolic risk factors among adolescent girls. AB - BACKGROUND: The purpose of this study was to examine the association between muscular fitness (MF), assessed by 2 components of Fitnessgram test battery, the Curl-Up and Push-Ups tests and the metabolic risk score among adolescent girls. METHODS: A total of 229 girls (aged 12-15 years old) comprised the sample of this study. Anthropometric data (height, body mass, waist circumference) were collected. Body mass index (BMI) was also calculated. Muscular strength was assessed taking into account the tests that comprised the FITNESSGRAM test battery, i.e. the curl-up and the push-up. Participants were then categorized in one of 3 categories according the number of tests in which they accomplished the scores that allow them to be classified in health or above health zone. The blood pressure [BP], fasting total cholesterol [TC], low density lipoprotein cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], triglycerides [TG], glucose, and a metabolic risk score (MRS) were also examined. Physical Activity Index (PAI) was obtained by questionnaire. RESULTS: Higher compliance with health-zone criteria (good in the 2 tests), adjusted for age and maturation, were positive and significantly (p or =5 years old in a prospective cohort as part of population based infectious disease surveillance in rural western Kenya from October 2006 September 2008. METHODS: Blood cultures were done on patients meeting pre-defined criteria--severe acute respiratory illness (SARI), fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates. RESULTS: Among 1,301 blood cultures among persons > or =5 years, 52 (4%) yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those > or =18 years than 5-17 years (6.9% versus 1.6%, p < 0.001). The highest yield was for inpatients with SARI (10%), compared with SARI outpatients (3%) and acute febrile outpatients (1%). Serotype 1 pneumococcus was most common (42% isolates) and 71% were serotypes included in the 10-valent pneumococcal conjugate vaccine (PCV10). Non-susceptibility to beta-lactam antibiotics was low (<5%), but to trimethoprim-sulfamethoxazole was high (>95%). The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61%) of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1). We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010. CONCLUSIONS: Pneumococcal bacteremia rates were high among persons > or =5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral treatment for HIV and introduction of PCV10 for Kenyan children (anticipated in late 2010) result in substantial secondary benefits by reducing pneumococcal disease in adults. PMID- 20573226 TI - Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets. AB - BACKGROUND: The routes by which humans acquire influenza H5N1 infections have not been fully elucidated. Based on the known biology of influenza viruses, four modes of transmission are most likely in humans: aerosol transmission, ingestion of undercooked contaminated infected poultry, transmission by large droplets and self-inoculation of the nasal mucosa by contaminated hands. In preparation of a study to resolve whether H5N1 viruses are transmissible by aerosol in an animal model that is a surrogate for humans, an inhalation exposure system for studies of aerosolized H5N1 viruses in ferrets was designed, assembled, and validated. Particular attention was paid towards system safety, efficacy of dissemination, the viability of aerosolized virus, and sampling methodology. RESULTS: An aerosol generation and delivery system, referred to as a Nose-Only Bioaerosol Exposure System (NBIES), was assembled and function tested. The NBIES passed all safety tests, met expected engineering parameters, required relatively small quantities of material to obtain the desired aerosol concentrations of influenza virus, and delivered doses with high-efficacy. Ferrets withstood a mock exposure trial without signs of stress. CONCLUSIONS: The NBIES delivers doses of aerosolized influenza viruses with high efficacy, and uses less starting material than other similar designs. Influenza H5N1 and H3N2 viruses remain stable under the conditions used for aerosol generation and sample collection. The NBIES is qualified for studies of aerosolized H5N1 virus. PMID- 20573227 TI - Assessment of mitral bioprostheses using cardiovascular magnetic resonance. AB - BACKGROUND: The orifice area of mitral bioprostheses provides important information regarding their hemodynamic performance. It is usually calculated by transthoracic echocardiography (TTE), however, accurate and reproducible determination may be challenging. Cardiovascular magnetic resonance (CMR) has been proven as an accurate alternative for assessing aortic bioprostheses. However, whether CMR can be similarly applied for bioprostheses in the mitral position, particularly in the presence of frequently coincident arrhythmias, is unclear. The aim of the study is to test the feasibility of CMR to evaluate the orifice area of mitral bioprostheses. METHODS: CMR planimetry was performed in 18 consecutive patients with mitral bioprostheses (n = 13 Hancock(R), n = 4 Labcore(R), n = 1 Perimount(R); mean time since implantation 4.5 +/- 3.9 years) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5T MR system. CMR results were compared with pressure half-time derived orifice areas obtained by TTE. RESULTS: Six subjects were in sinus rhythm, 11 in atrial fibrillation, and 1 exhibited frequent ventricular extrasystoles. CMR image quality was rated as good in 10, moderate in 6, and significantly impaired in 2 subjects. In one prosthetic type (Perimount(R)), strong stent artifacts occurred. Orifice areas by CMR (mean 2.1 +/- 0.3 cm2) and TTE (mean 2.1 +/- 0.3 cm2) correlated significantly (r = 0.94; p < 0.001). Bland-Altman analysis showed a 95% confidence interval from -0.16 to 0.28 cm2 (mean difference 0.06 +/- 0.11 cm2; range -0.1 to 0.3 cm2). Intra- and inter-observer variabilities of CMR planimetry were 4.5 +/- 2.9% and 7.9 +/- 5.2%. CONCLUSIONS: The assessment of mitral bioprostheses using CMR is feasible even in those with arrhythmias, providing orifice areas with close agreement to echocardiography and low observer dependency. Larger samples with a greater variety of prosthetic types and more cases of prosthetic dysfunction are required to confirm these preliminary results. PMID- 20573228 TI - Mapping the risk of avian influenza in wild birds in the US. AB - BACKGROUND: Avian influenza virus (AIV) is an important public health issue because pandemic influenza viruses in people have contained genes from viruses that infect birds. The H5 and H7 AIV subtypes have periodically mutated from low pathogenicity to high pathogenicity form. Analysis of the geographic distribution of AIV can identify areas where reassortment events might occur and how high pathogenicity influenza might travel if it enters wild bird populations in the US. Modelling the number of AIV cases is important because the rate of co infection with multiple AIV subtypes increases with the number of cases and co infection is the source of reassortment events that give rise to new strains of influenza, which occurred before the 1968 pandemic. Aquatic birds in the orders Anseriformes and Charadriiformes have been recognized as reservoirs of AIV since the 1970s. However, little is known about influenza prevalence in terrestrial birds in the order Passeriformes. Since passerines share the same habitat as poultry, they may be more effective transmitters of the disease to humans than aquatic birds. We analyze 152 passerine species including the American Robin (Turdus migratorius) and Swainson's Thrush (Catharus ustulatus). METHODS: We formulate a regression model to predict AIV cases throughout the US at the county scale as a function of 12 environmental variables, sampling effort, and proximity to other counties with influenza outbreaks. Our analysis did not distinguish between types of influenza, including low or highly pathogenic forms. RESULTS: Analysis of 13,046 cloacal samples collected from 225 bird species in 41 US states between 2005 and 2008 indicates that the average prevalence of influenza in passerines is greater than the prevalence in eight other avian orders. Our regression model identifies the Great Plains and the Pacific Northwest as high risk areas for AIV. Highly significant predictors of AIV include the amount of harvested cropland and the first day of the year when a county is snow free. CONCLUSIONS: Although the prevalence of influenza in waterfowl has long been appreciated, we show that 22 species of song birds and perching birds (order Passeriformes) are influenza reservoirs in the contiguous US. PMID- 20573230 TI - An exploratory investigation of the influence of publication on translational medicine research. AB - BACKGROUND: Changes in clinical practice are brought about by the weight of clinical evidence for and against an intervention. Clinical evidence of efficacy relies on the dissemination of research results, usually by publication in medical journals which is often seen as a pre-requisite for progression of an intervention through further clinical trials or implementation studies. HOW FAR HAS RESEARCH PROGRESSED ALONG THE TRANSLATIONAL PATHWAY?: We undertook an exploratory exercise to determine where basic and translational medical research is currently published. Original research articles (329 in total) published in high impact general and specialist medical journals were classified into different stages of research within the translational medicine pathway. WHERE IS TRANSLATIONAL RESEARCH PUBLISHED?: The general medical journals had the broadest spread of published research over the translational pathway. The specialist journals tended to be positioned to disseminate the research findings of early stage translational research from basic science results through to early stages of clinical testing. CONCLUSION: It is not possible for one journal to satisfy all the needs of the reader and the author along the translational medicine pathway. For an intervention to progress along the translational pathway background information should be readily accessible in the article. This pathway is currently being actively managed by the funding agencies but the next challenge is to ensure the pathway operates efficiently and does not allow promising innovations to languish and to provide a smoother transition for interventions to reach the clinic in a quicker timescale. It is clear that the dissemination of results in the right place at the right time is crucial to the transition of an intervention from the laboratory to clinical practice. PMID- 20573229 TI - Silver-Russell syndrome: genetic basis and molecular genetic testing. AB - Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth that are rooted in the prenatal period. Therefore it is predictable that many of the so far known congenital imprinting disorders (IDs) are clinically characterised by growth disturbances. A noteable imprinting disorder is Silver-Russell syndrome (SRS), a congenital disease characterised by intrauterine and postnatal growth retardation, relative macrocephaly, a typical triangular face, asymmetry and further less characteristic features. However, the clinical spectrum is broad and the clinical diagnosis often subjective. Genetic and epigenetic disturbances can meanwhile be detected in approximately 50% of patients with typical SRS features. Nearly one tenth of patients carry a maternal uniparental disomy of chromosome 7 (UPD(7)mat), more than 38% show a hypomethylation in the imprinting control region 1 in 11p15. More than 1% of patients show (sub)microscopic chromosomal aberrations. Interestingly, in approximately 7% of 11p15 hypomethylation carriers, demethylation of other imprinted loci can be detected. Clinically, these patients do not differ from those with isolated 11p15 hypomethylation whereas the UPD(7)mat patients generally show a milder phenotype. However, an unambiguous (epi)genotype phenotype correlation can not be delineated.We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7)mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease. PMID- 20573231 TI - Bone morphogenetic protein (BMP)-4 and BMP-7 regulate differentially transforming growth factor (TGF)-beta1 in normal human lung fibroblasts (NHLF). AB - BACKGROUND: Airway remodelling is thought to be under the control of a complex group of molecules belonging to the transforming growth factor (TGF)-superfamily. The bone morphogenetic proteins (BMPs) belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-beta-induced profibrotic functions in lung fibroblasts. METHODS: Cell cultures were exposed to TGF-beta1 alone or in the presence of BMP 4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF) was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of alpha-smooth muscle actin (alpha-SMA) by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP) activity was assessed by zymography. RESULTS: We have demonstrated TGF beta1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-beta1-induced extracellular matrix protein production. TGF-beta1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-beta1-induced MMP 13 release compared to untreated and TGF-beta1-treated cells. TGF-beta1 also induced a myofibroblast-like transformation which was partially inhibited by BMP 7 but not BMP-4. CONCLUSIONS: Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for BMP-4 in the regulation of lung fibroblast function. PMID- 20573232 TI - Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-beta signaling. AB - BACKGROUND: Germline mutations in the FLCN gene are responsible for the development of fibrofolliculomas, lung cysts and renal neoplasia in Birt-Hogg Dube' (BHD) syndrome. The encoded protein folliculin (FLCN) is conserved across species but contains no classic motifs or domains and its function remains unknown. Somatic mutations or loss of heterozygosity in the remaining wild type copy of the FLCN gene have been found in renal tumors from BHD patients suggesting that FLCN is a classic tumor suppressor gene. RESULTS: To examine the tumor suppressor function of FLCN, wild-type or mutant FLCN (H255R) was stably expressed in a FLCN-null renal tumor cell line, UOK257, derived from a BHD patient. When these cells were injected into nude mice, tumor development was inversely dependent upon the level of wild-type FLCN expression. We identified genes that were differentially expressed in the cell lines with or without wild type FLCN, many of which are involved in TGF-beta signaling, including TGF-beta2 (TGFB2), inhibin beta A chain (INHBA), thrombospondin 1 (THBS1), gremlin (GREM1), and SMAD3. In support of the in vitro data, TGFB2, INHBA, THBS1 and SMAD3 expression levels were significantly lower in BHD-associated renal tumors compared with normal kidney tissue. Although receptor mediated SMAD phosphorylation was not affected, basal and maximal TGF-beta-induced levels of TGFB2, INHBA and SMAD7 were dramatically reduced in FLCN-null cells compared with FLCN-restored cells. Secreted TGF-beta2 and activin A (homo-dimer of INHBA) protein levels were also lower in FLCN-null cells compared with FLCN-restored cells. Consistent with a growth suppressive function, activin A (but not TGF beta2) completely suppressed anchorage-independent growth of FLCN-null UOK257 cells. CONCLUSIONS: Our data demonstrate a role for FLCN in the regulation of key molecules in TGF-beta signaling and confirm deregulation of their expression in BHD-associated renal tumors. Thus, deregulation of genes involved in TGF-beta signaling by FLCN inactivation is likely to be an important step for tumorigenesis in BHD syndrome. PMID- 20573233 TI - Designing verbal autopsy studies. AB - BACKGROUND: Verbal autopsy analyses are widely used for estimating cause-specific mortality rates (CSMR) in the vast majority of the world without high-quality medical death registration. Verbal autopsies -- survey interviews with the caretakers of imminent decedents -- stand in for medical examinations or physical autopsies, which are infeasible or culturally prohibited. METHODS AND FINDINGS: We introduce methods, simulations, and interpretations that can improve the design of automated, data-derived estimates of CSMRs, building on a new approach by King and Lu (2008). Our results generate advice for choosing symptom questions and sample sizes that is easier to satisfy than existing practices. For example, most prior effort has been devoted to searching for symptoms with high sensitivity and specificity, which has rarely if ever succeeded with multiple causes of death. In contrast, our approach makes this search irrelevant because it can produce unbiased estimates even with symptoms that have very low sensitivity and specificity. In addition, the new method is optimized for survey questions caretakers can easily answer rather than questions physicians would ask themselves. We also offer an automated method of weeding out biased symptom questions and advice on how to choose the number of causes of death, symptom questions to ask, and observations to collect, among others. CONCLUSIONS: With the advice offered here, researchers should be able to design verbal autopsy surveys and conduct analyses with greatly reduced statistical biases and research costs. PMID- 20573234 TI - Infection with hepatitis B virus carrying novel pre-S/S gene mutations in female siblings vaccinated at birth: two case reports. AB - INTRODUCTION: After the initiation of a mass hepatitis B vaccination program in Taiwan, the prevalence of hepatitis B virus infection has declined progressively. However, about 1 percent of the young generation, who received hepatitis B vaccination at birth, remain carriers. Infection with vaccine-escape hepatitis B virus mutants always occurs shortly after birth. Here, we report two female siblings in whom the infection occurred in their adolescence. This report raises the question of whether a booster for hepatitis B vaccination is needed. CASE PRESENTATION: Two 19 and 14-year-old Taiwanese female siblings were born to a mother infected with hepatitis B virus and received a complete course of hepatitis B vaccination at birth. They remained negative for serum hepatitis B surface antigen and positive for serum anti-hepatitis B surface antibody throughout their childhood. However, both were infected with the hepatitis B virus in their adolescence. Hepatitis B virus DNA was extracted from serum samples from the mother and two siblings. Hepatitis B virus pre-S/S sequence was amplified by polymerase chain reaction followed by nucleotide sequencing. When compared with the sequence obtained from the mother, multiple amino acid substitutions located near or in the major hydrophilic region of the surface antigen were identified in the elder sister. Four of these mutations (sL97S, sL98S, sG102R, and sA159P) were novel. A novel in-frame deletion (14 amino acids deleted, pre-S 127-140) was found in the hepatitis B virus pre-S2 region in the younger sister. CONCLUSIONS: Despite having received hepatitis B vaccination at birth, hepatitis B virus infection can still occur in adolescence with the emergence of novel mutations in the pre-S/S gene. This is a rare event and, to the best of our knowledge, has not been previously reported. PMID- 20573235 TI - A spoonful of math helps the medicine go down: an illustration of how healthcare can benefit from mathematical modeling and analysis. AB - OBJECTIVES: A recent joint report from the Institute of Medicine and the National Academy of Engineering, highlights the benefits of--indeed, the need for- mathematical analysis of healthcare delivery. Tools for such analysis have been developed over decades by researchers in Operations Research (OR). An OR perspective typically frames a complex problem in terms of its essential mathematical structure. This article illustrates the use and value of the tools of operations research in healthcare. It reviews one OR tool, queueing theory, and provides an illustration involving a hypothetical drug treatment facility. METHOD: Queueing Theory (QT) is the study of waiting lines. The theory is useful in that it provides solutions to problems of waiting and its relationship to key characteristics of healthcare systems. More generally, it illustrates the strengths of modeling in healthcare and service delivery.Queueing theory offers insights that initially may be hidden. For example, a queueing model allows one to incorporate randomness, which is inherent in the actual system, into the mathematical analysis. As a result of this randomness, these systems often perform much worse than one might have guessed based on deterministic conditions. Poor performance is reflected in longer lines, longer waits, and lower levels of server utilization.As an illustration, we specify a queueing model of a representative drug treatment facility. The analysis of this model provides mathematical expressions for some of the key performance measures, such as average waiting time for admission. RESULTS: We calculate average occupancy in the facility and its relationship to system characteristics. For example, when the facility has 28 beds, the average wait for admission is 4 days. We also explore the relationship between arrival rate at the facility, the capacity of the facility, and waiting times. CONCLUSIONS: One key aspect of the healthcare system is its complexity, and policy makers want to design and reform the system in a way that affects competing goals. OR methodologies, particularly queueing theory, can be very useful in gaining deeper understanding of this complexity and exploring the potential effects of proposed changes on the system without making any actual changes. PMID- 20573236 TI - Measuring the impact and costs of a universal group based parenting programme: protocol and implementation of a trial. AB - BACKGROUND: Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. METHODS/DESIGN: A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. DISCUSSION: Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13919732. PMID- 20573237 TI - Physical activity and optimal self-rated health of adults with and without diabetes. AB - BACKGROUND: Regular physical activity can improve people's overall health and contribute to both primary and secondary prevention of many chronic diseases and conditions including diabetes. The aim of this study was to examine the association between levels of physical activity and optimal self-rated health (SRH) of U.S. adults with and without diabetes in all 50 states and territories of the Unites States. METHODS: We estimated the prevalence of optimal SRH by diabetes status of 430,912 adults aged 18 years and older who participated in the 2007 state-based survey of the Behavioral Risk Factor Surveillance System (BRFSS). Prevalence ratios were produced with multivariate Cox regression models using levels of physical activity as a predictor and status of optimal SRH as an outcome variable while controlling for sociodemographic and behavioral health risk factors. RESULTS: The prevalence of reporting optimal SRH was 53.3%, 52.2%, and 86.2% for adults with type 1 diabetes, type 2 diabetes, and without diabetes, respectively. Also in the aforementioned order, adults who reported being active had an increased likelihood of 81%, 32%, and 18% for reporting optimal SRH, when compared with adults who reported being inactive. CONCLUSIONS: Regular physical activity of adults, particularly adults with diabetes, is associated with optimal SRH. The findings of this study underscore the importance of advising and motivating adults with diabetes so that physical activity can be integrated into their lifestyle for diabetes care. Additionally, a population-based effort to promote physical activity in communities may benefit adults in general by improving their overall health and well-being. PMID- 20573238 TI - A high-throughput pipeline for the design of real-time PCR signatures. AB - BACKGROUND: Pathogen diagnostic assays based on polymerase chain reaction (PCR) technology provide high sensitivity and specificity. However, the design of these diagnostic assays is computationally intensive, requiring high-throughput methods to identify unique PCR signatures in the presence of an ever increasing availability of sequenced genomes. RESULTS: We present the Tool for PCR Signature Identification (TOPSI), a high-performance computing pipeline for the design of PCR-based pathogen diagnostic assays. The TOPSI pipeline efficiently designs PCR signatures common to multiple bacterial genomes by obtaining the shared regions through pairwise alignments between the input genomes. TOPSI successfully designed PCR signatures common to 18 Staphylococcus aureus genomes in less than 14 hours using 98 cores on a high-performance computing system. CONCLUSIONS: TOPSI is a computationally efficient, fully integrated tool for high-throughput design of PCR signatures common to multiple bacterial genomes. TOPSI is freely available for download at http://www.bhsai.org/downloads/topsi.tar.gz. PMID- 20573239 TI - Molecular evolution of genes in avian genomes. AB - BACKGROUND: Obtaining a draft genome sequence of the zebra finch (Taeniopygia guttata), the second bird genome to be sequenced, provides the necessary resource for whole-genome comparative analysis of gene sequence evolution in a non mammalian vertebrate lineage. To analyze basic molecular evolutionary processes during avian evolution, and to contrast these with the situation in mammals, we aligned the protein-coding sequences of 8,384 1:1 orthologs of chicken, zebra finch, a lizard and three mammalian species. RESULTS: We found clear differences in the substitution rate at fourfold degenerate sites, being lowest in the ancestral bird lineage, intermediate in the chicken lineage and highest in the zebra finch lineage, possibly reflecting differences in generation time. We identified positively selected and/or rapidly evolving genes in avian lineages and found an over-representation of several functional classes, including anion transporter activity, calcium ion binding, cell adhesion and microtubule cytoskeleton. CONCLUSIONS: Focusing specifically on genes of neurological interest and genes differentially expressed in the unique vocal control nuclei of the songbird brain, we find a number of positively selected genes, including synaptic receptors. We found no evidence that selection for beneficial alleles is more efficient in regions of high recombination; in fact, there was a weak yet significant negative correlation between omega and recombination rate, which is in the direction predicted by the Hill-Robertson effect if slightly deleterious mutations contribute to protein evolution. These findings set the stage for studies of functional genetics of avian genes. PMID- 20573240 TI - Tumor promoting effects of CD95 signaling in chemoresistant cells. AB - BACKGROUND: CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. The aim of this study was to characterize some key cellular responses controlled by CD95 signaling in oxaliplatin-resistant colon cancer cells. RESULTS: We show that CD95 triggering results in an increased metastatic ability in resistant cells. Moreover, oxaliplatin treatment itself stimulates cell migration and decreases cell adhesion through CD95 activation, since CD95 expression inhibition by siRNA blocks the promigratory effects of oxaliplatin. These promigratory effects are related to the epithelia-to-mesenchymal transition (EMT) phenomenon, as evidenced by the up-regulation of some transcription factors and mesenchymal markers both in vitro and in vivo. CONCLUSIONS: We conclude that oxaliplatin treatment in cells that have acquired resistance to oxaliplatin-induced apoptosis results in tumor-promoting effects through the activation of CD95 signaling and by inducing EMT, all these events jointly contributing to a metastatic phenotype. PMID- 20573241 TI - Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications. AB - BACKGROUND: Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP. METHODS: Ten patients with type 1 diabetes and ten healthy age- and weight-matched controls were studied. Aqueous flow was measured by fluorophotometry during a hyperinsulinemic-euglycemic clamp (insulin 2 mU/kg/min). Intraocular pressure was measured by tonometry at -10, 90 and 240 minutes from the start of the clamp, and outflow facility was measured by tonography at 240 minutes. RESULTS: During conditions of identical glucose and insulin concentrations, mean aqueous flow was lower by 0.58 microl/min in the diabetes group compared to controls (2.58 +/- 0.65 versus 3.16 +/- 0.66 microl/min, respectively, mean +/- SD, p = 0.07) but statistical significance was not reached. Before the clamp, IOP was higher in the diabetes group (22.6 +/- 3.0 mm Hg) than in the control group (19.3 +/- 1.8 mm Hg, p = 0.01) but at 90 minutes into the clamp, and for the remainder of the study, IOP was reduced in the diabetes group to the level of the control group. Ocular pulse amplitude and outflow facility were not different between groups. Systolic blood pressure was significantly higher in the diabetes group, but diastolic and mean arterial pressures were not different. CONCLUSIONS: We conclude that compared to healthy participants, patients with type 1 diabetes having microalbuminuria and retinopathy have higher IOPs that are normalized by hyperinsulinemia. During the clamp, a reduction in aqueous flow was not statistically significant. PMID- 20573242 TI - The relationship between mosquito abundance and rice field density in the Republic of Korea. AB - BACKGROUND: Japanese encephalitis virus (JEV), the causative agent of Japanese encephalitis (JE), is endemic to the Republic of Korea (ROK) where unvaccinated United States (U.S.) military Service members, civilians and family members are stationed. The primary vector of the JEV in the ROK is Culex tritaeniorhynchus. The ecological relationship between Culex spp. and rice fields has been studied extensively; rice fields have been shown to increase the prevalence of Cx. tritaeniorhynchus. This research was conducted to determine if the quantification of rice field land cover surrounding U.S. military installations in the ROK should be used as a parameter in a larger risk model that predicts the abundance of Cx. tritaeniorhynchus populations. Mosquito data from the U.S. Forces Korea (USFK) mosquito surveillance program were used in this project. The average number of female Cx. tritaeniorhynchus collected per trap night for the months of August and September, 2002-2008, was calculated. Rice fields were manually digitized inside 1.5 km buffer zones surrounding U.S. military installations on high-resolution satellite images, and the proportion of rice fields was calculated for each buffer zone. RESULTS: Mosquito data collected from seventeen sample sites were analyzed for an association with the proportion of rice field land cover. Results demonstrated that the linear relationship between the proportion of rice fields and mosquito abundance was statistically significant (R2 = 0.62, r = .79, F = 22.72, p < 0.001). CONCLUSIONS: The analysis presented shows a statistically significant linear relationship between the two parameters, proportion of rice field land cover and log10 of the average number of Cx. tritaeniorhynchus collected per trap night. The findings confirm that agricultural land cover should be included in future studies to develop JE risk prediction models for non-indigenous personnel living at military installations in the ROK. PMID- 20573243 TI - Predictors of mortality among elderly people living in a south Indian urban community; a 10/66 Dementia Research Group prospective population-based cohort study. AB - BACKGROUND: Eighty percent of deaths occur in low and middle income countries (LMIC), where chronic diseases are the leading cause. Most of these deaths are of older people, but there is little information on the extent, pattern and predictors of their mortality. We studied these among people aged 65 years and over living in urban catchment areas in Chennai, south India. METHODS: In a prospective population cohort study, 1005 participants were followed-up after three years. Baseline assessment included sociodemographic and socioeconomic characteristics, health behaviours, physical, mental and cognitive disorders, disability and subjective global health. RESULTS: At follow-up, 257 (25.6%) were not traced. Baseline characteristics were similar to the 748 whose vital status was ascertained; 154 (20.6%) had died. The mortality rate was 92.5/1,000 per annum for men and 51.0/1,000 per annum for women. Adjusting for age and sex, mortality was associated with older age, male sex, having no friends, physical inactivity, smaller arm circumference, dementia, depression, poor self-rated health and disability. A parsimonious model included, in order of aetiologic force, male sex, smaller arm circumference, age, disability, and dementia. The total population attributable risk fraction was 0.90. CONCLUSION: A balanced approach to prevention of chronic disease deaths requires some attention to proximal risk factors in older people. Smoking and obesity seem much less relevant than in younger people. Undernutrition is preventable. While dementia makes the largest contribution to disability and dependency, comorbidity is the rule, and more attention should be given to the chronic care needs of those affected, and their carers. PMID- 20573244 TI - High-affinity consensus binding of target RNAs by the STAR/GSG proteins GLD-1, STAR-2 and Quaking. AB - BACKGROUND: STAR/GSG proteins regulate gene expression in metazoans by binding consensus sites in the 5' or 3' UTRs of target mRNA transcripts. Owing to the high degree of homology across the STAR domain, most STAR proteins recognize similar RNA consensus sequences. Previously, the consensus for a number of well characterized STAR proteins was defined as a hexameric sequence, referred to as the SBE, for STAR protein binding element. C. elegans GLD-1 and mouse Quaking (Qk 1) are two representative STAR proteins that bind similar consensus hexamers, which differ only in the preferred nucleotide identities at certain positions. Earlier reports also identified partial consensus elements located upstream or downstream of a canonical consensus hexamer in target RNAs, although the relative contribution of these sequences to the overall binding energy remains less well understood. Additionally, a recently identified STAR protein called STAR-2 from C. elegans is thought to bind target RNA consensus sites similar to that of GLD-1 and Qk-1. RESULTS: Here, a combination of fluorescence-polarization and gel mobility shift assays was used to demonstrate that STAR-2 binds to a similar RNA consensus as GLD-1 and Qk-1. These assays were also used to further delineate the contributions of each hexamer consensus nucleotide to high-affinity binding by GLD-1, Qk-1 and STAR-2 in a variety of RNA contexts. In addition, the effects of inserting additional full or partial consensus elements upstream or downstream of a canonical hexamer in target RNAs were also measured to better define the sequence elements and RNA architecture recognized by different STAR proteins. CONCLUSIONS: The results presented here indicate that a single hexameric consensus is sufficient for high-affinity RNA binding by STAR proteins, and that upstream or downstream partial consensus elements may alter binding affinities depending on the sequence and spacing. The general requirements determined for high-affinity RNA binding by STAR proteins will help facilitate the identification of novel regulatory targets in vivo. PMID- 20573245 TI - Concentration of acrylamide in a polyacrylamide gel affects VP4 gene coding assignment of group A equine rotavirus strains with P[12] specificity. AB - BACKGROUND: It is universally acknowledged that genome segment 4 of group A rotavirus, the major etiologic agent of severe diarrhea in infants and neonatal farm animals, encodes outer capsid neutralization and protective antigen VP4. RESULTS: To determine which genome segment of three group A equine rotavirus strains (H-2, FI-14 and FI-23) with P[12] specificity encodes the VP4, we analyzed dsRNAs of strains H-2, FI-14 and FI-23 as well as their reassortants by polyacrylamide gel electrophoresis (PAGE) at varying concentrations of acrylamide. The relative position of the VP4 gene of the three equine P[12] strains varied (either genome segment 3 or 4) depending upon the concentration of acrylamide. The VP4 gene bearing P[3], P[4], P[6], P[7], P[8] or P[18] specificity did not exhibit this phenomenon when the PAGE running conditions were varied. CONCLUSIONS: The concentration of acrylamide in a PAGE gel affected VP4 gene coding assignment of equine rotavirus strains bearing P[12] specificity. PMID- 20573246 TI - Reduced susceptibility to selected synthetic pyrethroids in urban malaria vector Anopheles stephensi: a case study in Mangalore city, South India. AB - BACKGROUND: Synthetic pyrethroids are potent insecticides most commonly used in the vector control programme. These are applied for indoor residual sprays, space sprays and in impregnated bed nets. Resistance reduces the efficacy of insecticides. Thus, the susceptibility status of the target vector(s) is monitored routinely to select the effective ones. A study was undertaken in a malaria endemic coastal city Mangalore, Karnataka, South India, against the known malaria vector Anopheles stephensi. METHODS: The susceptibility status was assessed at diagnostic doses of DDT (4%), malathion (5%), deltamethrin (0.05%), cyfluthrin (0.15%), alphacypermethrin (0.10%), lambdacyhalothrin (0.05%) and permethrin (0.75%) using the standard WHO tube test method during October/November 2006. RESULTS: Anopheles stephensi was resistant to malathion by 54.9%, but tolerant to deltamethrin by 86.1%, cyfluthrin 95.5% and alphacypermethrin 90.6%, whereas it was susceptible to DDT by 98.1%, lambdacyhalothrin 98.6% and permethrin 100.0%, respectively. The KDT50 and KDT95 values for these insecticides also showed the similar responses. CONCLUSION: Susceptibility of An. stephensi to DDT is an important finding as this has never been used in Mangalore city, whereas its rural counterpart Anopheles culicifacies is widely resistant to this insecticide. The study explores the selection and rotation of the appropriate insecticide molecule even within the same group for effective vector management. PMID- 20573247 TI - Chronic consumption of fructose rich soft drinks alters tissue lipids of rats. AB - BACKGROUND: Fructose-based diets are apparently related to the occurrence of several metabolic dysfunctions, but the effects of the consumption of high amounts of fructose on body tissues have not been well described. The aim of this study was to analyze the general characteristics and the lipid content of different tissues of rats after chronic ingestion of a fructose rich soft drink. METHODS: Forty-five Wistar rats were used. The rats were divided into three groups (n = 15) and allowed to consume water (C), light Coca Cola (R) (L) or regular Coca Cola(R) (R) as the sole source of liquids for eight weeks. RESULTS: The R group presented significantly higher daily liquid intake and significantly lower food intake than the C and L groups. Moreover, relative to the C and L groups, the R group showed higher triglyceride concentrations in the serum and liver. However, the L group animals presented lower values of serum triglycerides and cholesterol than controls. CONCLUSIONS: Based on the results, it can be concluded that daily ingestion of a large amount of fructose- rich soft drink resulted in unfavorable alterations to the lipid profile of the rats. PMID- 20573248 TI - TagCleaner: Identification and removal of tag sequences from genomic and metagenomic datasets. AB - BACKGROUND: Sequencing metagenomes that were pre-amplified with primer-based methods requires the removal of the additional tag sequences from the datasets. The sequenced reads can contain deletions or insertions due to sequencing limitations, and the primer sequence may contain ambiguous bases. Furthermore, the tag sequence may be unavailable or incorrectly reported. Because of the potential for downstream inaccuracies introduced by unwanted sequence contaminations, it is important to use reliable tools for pre-processing sequence data. RESULTS: TagCleaner is a web application developed to automatically identify and remove known or unknown tag sequences allowing insertions and deletions in the dataset. TagCleaner is designed to filter the trimmed reads for duplicates, short reads, and reads with high rates of ambiguous sequences. An additional screening for and splitting of fragment-to-fragment concatenations that gave rise to artificial concatenated sequences can increase the quality of the dataset. Users may modify the different filter parameters according to their own preferences. CONCLUSIONS: TagCleaner is a publicly available web application that is able to automatically detect and efficiently remove tag sequences from metagenomic datasets. It is easily configurable and provides a user-friendly interface. The interactive web interface facilitates export functionality for subsequent data processing, and is available at http://edwards.sdsu.edu/tagcleaner. PMID- 20573249 TI - Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance. AB - BACKGROUND: Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (SA index) for the identification of IR and related metabolic conditions. METHODS: A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the SA index were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated. RESULTS: The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 vs. 0.669, P = 0.74), obesity (0.592 vs. 0.610, P = 0.32), hypertriglyceridemia (0.661 vs. 0.671, P = 0.50) and hypoalphalipoproteinemia (0.624 vs. 0.633, P = 0.58) were similar. A total adiponectin level of 8.03 mug/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 mug/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.The area under the ROC curve of the SA index for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536 0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677]. CONCLUSIONS: Total adiponectin, HMWA and the SA index had similar utility for the identification of IR and metabolic disturbances. PMID- 20573250 TI - Determinants of male involvement in the prevention of mother-to-child transmission of HIV programme in Eastern Uganda: a cross-sectional survey. AB - BACKGROUND: Mother-to-child transmission of HIV (MTCT) accounts for over 95% of all paediatric HIV infections worldwide. Several studies have shown that male participation in the antenatal care of their spouses together with couple counselling and testing for HIV, increases use of the interventions for HIV prevention. The prevention programme of MTCT (PMTCT) was launched in Uganda in 2000 and Mbale in 2002. Less than 10% of the pregnant women accepted antenatal HIV testing at Mbale Regional Referral Hospital in 2003; couple counselling and testing for HIV was low. Therefore, we conducted the study to determine the level of male involvement and identify its determinants in the PMTCT programme. METHODS: A cross-sectional survey of 388 men aged 18 years or more, whose spouses were attending antenatal care at Mbale Regional Referral Hospital, was conducted in Mbale district, Eastern Uganda. A male involvement index was constructed based on 6 questions. The survey was complemented by eight focus group discussions and five in-depth interviews. RESULTS: The respondents had a median age of 32 years (inter-quartile range, IQR: 28-37). The majority (74%) had a low male involvement index and only 5% of men accompanied their spouses to the antenatal clinic. Men who had attained secondary education were more likely to have a high male involvement index (OR: 1.9, 95% CI: 1.1-3.3) than those who had primary or no formal education. The respondents, whose occupation was driver (OR: 0.3, 95% CI: 0.1-0.7) or those who had fear of disclosure of their HIV sero-status results to their spouses (OR: 0.4, 95% CI: 0.2-0.8), were less likely to have a high male involvement index. Barriers to male involvement in the PMTCT programme were related to both the poor health system, to socio-economic factors and to cultural beliefs. CONCLUSIONS: Structural and cultural barriers to men's involvement in the PMTCT programme in Mbale district were complex and interrelated. Community sensitization of men about the benefits of antenatal care and PMTCT and improving client-friendliness in the clinics needs to be prioritised in order to improve low male participation and mitigate the effect of socio-economic and cultural factors. PMID- 20573251 TI - TabSQL: a MySQL tool to facilitate mapping user data to public databases. AB - BACKGROUND: With advances in high-throughput genomics and proteomics, it is challenging for biologists to deal with large data files and to map their data to annotations in public databases. RESULTS: We developed TabSQL, a MySQL-based application tool, for viewing, filtering and querying data files with large numbers of rows. TabSQL provides functions for downloading and installing table files from public databases including the Gene Ontology database (GO), the Ensembl databases, and genome databases from the UCSC genome bioinformatics site. Any other database that provides tab-delimited flat files can also be imported. The downloaded gene annotation tables can be queried together with users' data in TabSQL using either a graphic interface or command line. CONCLUSIONS: TabSQL allows queries across the user's data and public databases without programming. It is a convenient tool for biologists to annotate and enrich their data. PMID- 20573252 TI - Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique. AB - BACKGROUND: Despite numerous investigations, the impact of tizanidine, an anti spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components. METHODS: A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed. RESULTS: Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine. CONCLUSIONS: Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects. PMID- 20573253 TI - The views of doctors in their first year of medical practice on the lasting impact of a preparation for house officer course they undertook as final year medical students. AB - BACKGROUND: The UK General Medical Council recommends that medical students have the opportunity of shadowing the outgoing new doctor whose post they will soon undertake. At the University of Nottingham the two-week shadowing period was preceded by two weeks of lectures/seminars wherein students followed sessions on topics such as common medical/surgical emergencies, contracts, time management, surviving the first two years of clinical practice, careers advice and so on. The present study aimed to gain a better knowledge and understanding of the lasting impact of a four-week preparation course for new Foundation Year 1 doctors [F1 s interns]. The objectives chosen to achieve this aim were: 1/ to determine the extent to which the lecture/seminar course and shadowing period achieved their stated aim of smoothing the transition from life as a medical student to work as a new doctor; 2/ to evaluate perceptions of the importance of various forms of knowledge in easing the transition between medical student and new doctor METHOD: In the spring of 2007, 90 graduates from Nottingham were randomly selected and then emailed a link to a short, online survey of quantitative and qualitative questions. Of these 76 responded. Analysis of quantitative data was carried out using SPSS 16.0 and employed McNemar's test. Analysis of the qualitative data was carried out using the constant comparative method. RESULTS: Only 31% of respondents strongly agreed or agreed that the lecture/seminar part of the course prepared them well for their first FY1 post; 14% agreed that during their first job they drew on the knowledge gained during the lecture/seminar course; 94% strongly agreed or agreed that the shadowing part of the course was more useful than the lecture/seminar part. Experiential knowledge gained in the shadowing was the most highly valued, followed by procedural knowledge with propositional knowledge coming far behind. CONCLUSIONS: Our study shows that new doctors retrospectively value most the knowledge they are able to transfer to the workplace and value least material which seems to repeat what they had learned for their final exams. PMID- 20573254 TI - The impact of social networks on knowledge transfer in long-term care facilities: Protocol for a study. AB - BACKGROUND: Social networks are theorized as significant influences in the innovation adoption and behavior change processes. Our understanding of how social networks operate within healthcare settings is limited. As a result, our ability to design optimal interventions that employ social networks as a method of fostering planned behavior change is also limited. Through this proposed project, we expect to contribute new knowledge about factors influencing uptake of knowledge translation interventions. OBJECTIVES: Our specific aims include: To collect social network data among staff in two long-term care (LTC) facilities; to characterize social networks in these units; and to describe how social networks influence uptake and use of feedback reports. METHODS AND DESIGN: In this prospective study, we will collect data on social networks in nursing units in two LTC facilities, and use social network analysis techniques to characterize and describe the networks. These data will be combined with data from a funded project to explore the impact of social networks on uptake and use of feedback reports. In this parent study, feedback reports using standardized resident assessment data are distributed on a monthly basis. Surveys are administered to assess report uptake. In the proposed project, we will collect data on social networks, analyzing the data using graphical and quantitative techniques. We will combine the social network data with survey data to assess the influence of social networks on uptake of feedback reports. DISCUSSION: This study will contribute to understanding mechanisms for knowledge sharing among staff on units to permit more efficient and effective intervention design. A growing number of studies in the social network literature suggest that social networks can be studied not only as influences on knowledge translation, but also as possible mechanisms for fostering knowledge translation. This study will contribute to building theory to design such interventions. PMID- 20573255 TI - The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. AB - BACKGROUND: Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3. RESULTS: The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues. CONCLUSION: These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients. PMID- 20573256 TI - Cystic colon duplication causing intussusception in a 25-year-old man: report of a case and review of the literature. AB - BACKGROUND: Colonic intussusception is a rare congenital abnormality, mostly manifesting before the age of two with abdominal pain and acute intestinal obstruction with or without bleeding. In adults it may occur idiopathically or due to an intraluminal tumor mass. CASE PRESENTATION: A 25-year-old man presented with an acute abdomen and severe crampy abdominal pain. The clinical picture mimicked acute appendicitis. Transabdominal ultrasound examination revealed a 5 cm circular mass in the right upper abdomen. The ensuing computed tomography suggested an intussusception in the ascending colon. Intraoperatively, no full thickness invagination was detected. Due to a hard, intraluminal tumor a standard right hemicolectomy with ileotransversostomy was performed. The histopathological analysis revealed a cystic colon duplication leading to mucosal invagination and obstruction. CONCLUSIONS: In adults, colon intussusception is a rare event causing approximately 1% of all acute intestinal obstructions. Unlike its preferentially nonsurgical management in children, a bowel intussusception in adults should be operated because an organic, often malignant lesion is present in most cases. PMID- 20573257 TI - Attitudes of US medical trainees towards neurology education: "Neurophobia" - a global issue. AB - BACKGROUND: Several studies in the United Kingdom and Asia have suggested that medical students and residents have particular difficulty in diagnosing and managing patients with neurological problems. Little recent information is available for US trainees. We examined whether students and residents at a US university have difficulty in dealing with patients with neurological problems, identified the perceived sources of these difficulties and provide suggestions for the development of an effective educational experience in neurology. METHODS: A questionnaire was administered to third and fourth year medical students at a US school of medicine and to residents of an internal medicine residency program affiliated with that school. Perceived difficulties with eight medical specialties, including neurology, were examined. Methods considered to be most useful for learning medicine were documented. Reasons why neurology is perceived as difficult and ways to improve neurological teaching were assessed. RESULTS: 152 surveys were completed. Participation rates varied, with medical students having higher response rates (> 50%) than medical residents (27%-48%). Respondents felt that neurology was the medical specialty they had least knowledge in (p < 0.001) and was most difficult (p < 0.001). Trainees also felt they had the least confidence when dealing with patients with neurological complaints (p < 0.001). Residents felt more competent in neurology than students (p < 0.001). The paramount reasons for perceived difficulties with neurology were the complexity of neuroanatomy, limited patient exposure and insufficient teaching. Transition from pre-clinical to clinical medicine led to a doubling of "poor" ratings for neurological teaching. Over 80% of the respondents felt that neurology teaching could be improved through greater exposure to patients and more bedside tutorials. CONCLUSIONS: Medical students and residents at this US medical university found neurology difficult. Although this is consistent with prior reports from Europe and Asia, studies in other universities are needed to confirm generalizability of these findings. The optimal opportunity for improvement is during the transition from preclinical to clinical years. Enhanced integration of basic neurosciences and clinical neurology with emphasis on increased bedside tutorials and patient exposure should improve teaching. Studies are needed to quantify the effect of these interventions on confidence of trainees when dealing with patients presenting with neurological complaints. PMID- 20573258 TI - Optimization and analysis of a quantitative real-time PCR-based technique to determine microRNA expression in formalin-fixed paraffin-embedded samples. AB - BACKGROUND: MicroRNAs (miRs) are non-coding RNA molecules involved in post transcriptional regulation, with diverse functions in tissue development, differentiation, cell proliferation and apoptosis. miRs may be less prone to degradation during formalin fixation, facilitating miR expression studies in formalin-fixed paraffin-embedded (FFPE) tissue. RESULTS: Our study demonstrates that the TaqMan Human MicroRNA Array v1.0 (Early Access) platform is suitable for miR expression analysis in FFPE tissue with a high reproducibility (correlation coefficients of 0.95 between duplicates, p < 0.00001) and outlines the optimal performance conditions of this platform using clinical FFPE samples. We also outline a method of data analysis looking at differences in miR abundance between FFPE and fresh-frozen samples. By dividing the profiled miR into abundance strata of high (Ct<30), medium (30 < or = Ct < or = 35), and low (Ct>35), we show that reproducibility between technical replicates, equivalent dilutions, and FFPE vs. frozen samples is best in the high abundance stratum. We also demonstrate that the miR expression profiles of FFPE samples are comparable to those of fresh frozen samples, with a correlation of up to 0.87 (p < 0.001), when examining all miRs, regardless of RNA extraction method used. Examining correlation coefficients between FFPE and fresh-frozen samples in terms of miR abundance reveals correlation coefficients of up to 0.32 (low abundance), 0.70 (medium abundance) and up to 0.97 (high abundance). CONCLUSION: Our study thus demonstrates the utility, reproducibility, and optimization steps needed in miR expression studies using FFPE samples on a high-throughput quantitative PCR-based miR platform, opening up a realm of research possibilities for retrospective studies. PMID- 20573259 TI - Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil. AB - BACKGROUND: Poor control of blood pressure leads to hypertension which is a major risk factor for development of cardiovascular disease. The present study aimed to explore possible mechanisms of elevation in blood pressure following consumption of heated vegetable oil. METHODS: Forty-two male Sprague-Dawley rats were equally divided into six groups: Group I (control)--normal rat chow, Group II--fresh soy oil, Group III--soy oil heated once, Group IV--soy oil heated twice, Group V--soy oil heated five times, Group VI--soy oil heated ten times. Blood pressure was measured at the baseline level and at a monthly interval for six months. Plasma nitric oxide, heme oxygenase and angiotensin-converting enzyme levels were measured prior to treatment, at month-three and month-six later. At the end of treatment, the rats were sacrificed and thoracic aortas were taken for measurement of vascular reactivity. RESULTS: Blood pressure increased significantly (p<0.01) in the repeatedly heated oil groups compared to the control and fresh soy oil groups. Consumption of diet containing repeatedly heated oil resulted higher plasma angiotensin-converting enzyme level and lower nitric oxide content and heme oxygenase concentration. Reheated soy oil groups exhibited attenuated relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. CONCLUSION: As a result of consumption of repeatedly heated soy oil, an elevation in blood pressure was observed which may be due to the quantitative changes in endothelium dependent and independent factors including enzymes directly involved in the regulation of blood pressure. PMID- 20573260 TI - Escape from X inactivation in mice and humans. AB - A subset of X-linked genes escapes silencing by X inactivation and is expressed from both X chromosomes in mammalian females. Species-specific differences in the identity of these genes have recently been discovered, suggesting a role in the evolution of sex differences. Chromatin analyses have aimed to discover how genes remain expressed within a repressive environment. PMID- 20573261 TI - Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. AB - BACKGROUND: Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H4 receptor (H4R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H4R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined. METHODS: Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H4R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis. RESULTS: Therapeutic H4R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL 13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction. CONCLUSIONS: These data demonstrate that therapeutic H4R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H4R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics. PMID- 20573262 TI - Association between neighborhood socioeconomic status and screen time among pre school children: a cross-sectional study. AB - BACKGROUND: Sedentary behavior is considered a separate construct from physical activity and engaging in sedentary behaviors results in health effects independent of physical activity levels. A major source of sedentary behavior in children is time spent viewing TV or movies, playing video games, and using computers. To date no study has examined the impact of neighborhood socioeconomic status (SES) on pre-school children's screen time behavior. METHODS: Proxy reports of weekday and weekend screen time (TV/movies, video games, and computer use) were completed by 1633 parents on their 4-5 year-old children in Edmonton, Alberta between November, 2005 and August, 2007. Postal codes were used to classified neighborhoods into low, medium or high SES. Multiple linear and logistic regression models were conducted to examine relationships between screen time and neighborhood SES. RESULTS: Girls living in low SES neighborhoods engaged in significantly more weekly overall screen time and TV/movie minutes compared to girls living in high SES neighborhoods. The same relationship was not observed in boys. Children living in low SES neighborhoods were significantly more likely to be video game users and less likely to be computer users compared to children living in high SES neighborhoods. Also, children living in medium SES neighborhoods were significantly less likely to be computer users compared to children living in high SES neighborhoods. CONCLUSIONS: Some consideration should be given to providing alternative activity opportunities for children, especially girls who live in lower SES neighborhoods. Also, future research should continue to investigate the independent effects of neighborhood SES on screen time as well as the potential mediating variables for this relationship. PMID- 20573263 TI - Contrasting patterns of phylogeographic relationships in sympatric sister species of ironclad beetles (Zopheridae: Phloeodes spp.) in California's Transverse Ranges. AB - BACKGROUND: Comparative phylogeography of sympatric sibling species provides an opportunity to isolate the effects of geography and demographics on the evolutionary history of two lineages over the same, known time scale. In the current study, we investigated the phylogeographic structure of two zopherid beetle species, Phloeodes diabolicus and P. plicatus, where their ranges overlap in California's Transverse Ranges. RESULTS: Although P. diabolicus and P. plicatus share similar habitats with largely overlapping distributions, the results of this study revealed different evolutionary histories for each species since divergence from their most recent common ancestor. In general, P. plicatus had higher genetic diversity, and more among population isolation than P. diabolicus. The mismatch distributions indicated that one major difference between the two species was the timing of population expansion. This result was consistent with genetic patterns revealed by the Phist values and genetic diversity. Lastly, there were no parallel genetic breaks at similar geographic barriers between the species. CONCLUSIONS: Our data revealed that differential demographics rather than geography were responsible for the genetic patterns of the two species. PMID- 20573265 TI - Sigma-1 receptor agonist fluvoxamine for postoperative delirium in older adults: report of three cases. AB - BACKGROUND: Postoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias. Drug treatment for postoperative delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects. METHODS: We report on a Japanese woman (an 86-year-old (open reduction and internal fixation of the right femoral neck fracture), and two Japanese men (an 86-year-old (abdominal aortic aneurysm stent grafting), and a 77-year-old (right upper lobectomy due to lung tumour)) in which the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the postoperative delirium of these patients. RESULTS: Delirium Rating Scale scores in these patients dramatically decreased after treatment with fluvoxamine. CONCLUSIONS: Doctors should consider fluvoxamine as an alternative approach to treating postoperative delirium in older patients in order to avoid the risk of side effects and increased mortality by antipsychotic drugs. PMID- 20573264 TI - A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia. AB - BACKGROUND: Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia. METHODS: A randomised, placebo controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day) were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day) or placebo (n = 20) in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Positive and Negative Syndrome Scale (PANSS) scores were measured. RESULTS: In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention) task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non smoking patients, were significantly improved by tropisetron trial. CONCLUSIONS: This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia. PMID- 20573266 TI - Prescribing practice for malaria following introduction of artemether lumefantrine in an urban area with declining endemicity in West Africa. AB - BACKGROUND: The decline in malaria coinciding with the introduction of newer, costly anti-malarials has prompted studies into the overtreatment for malaria mostly in East Africa. The study presented here describes prescribing practices for malaria at health facilities in a West African country. METHODS: Cross sectional surveys were carried out in two urban Gambian primary health facilities (PHFs) during and outside the malaria transmission season. Facilities were comparable in terms of the staffing compliment and capability to perform slide microscopy. Patients treated for malaria were enrolled after consultations and blood smears collected and read at a reference laboratory. Slide reading results from the PHFs were compared to the reference readings and the proportion of cases treated but with a negative test result at the reference laboratory was determined. RESULTS: Slide requests were made for 33.2% (173) of those enrolled, being more frequent in children (0-15 yrs) than adults during the wet season (p = 0.003). In the same period, requests were commoner in under-fives compared to older children (p = 0.022); however, a positive test result was 4.4 times more likely in the latter group (p = 0.010). Parasitaemia was confirmed for only 4.7% (10/215) and 12.5% (37/297) of patients in the dry and wet seasons, respectively. The negative predictive value of a PHF slide remained above 97% in both seasons. CONCLUSIONS: The study provides evidence for considerable overtreatment for malaria in a West African setting comparable to reports from areas with similar low malaria transmission in East Africa. The data suggest that laboratory facilities may be under-used, and that adherence to negative PHF slide results could significantly reduce the degree of overtreatment. The "peak prevalence" in 5-15 year olds may reflect successful implementation of malaria control interventions in under-fives, but point out the need to extend such interventions to older children. PMID- 20573267 TI - Interventions for renal vasculitis in adults. A systematic review. AB - BACKGROUND: Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults. METHODS: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes. RESULTS: Twenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegener's granulomatosis. CONCLUSIONS: Plasma exchange is effective in patients with severe ARF secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil are also effective. Azathioprine, methotrexate and leflunomide are effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy. PMID- 20573268 TI - Diverse set of microRNAs are responsive to powdery mildew infection and heat stress in wheat (Triticum aestivum L.). AB - BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. MiRNAs can have large-scale regulatory effects on development and stress response in plants. RESULTS: To test whether miRNAs play roles in regulating response to powdery mildew infection and heat stress in wheat, by using Solexa high-throughput sequencing we cloned the small RNA from wheat leaves infected by preponderant physiological strain Erysiphe graminis f. sp. tritici (Egt) or by heat stress treatment. A total of 153 miRNAs were identified, which belong to 51 known and 81 novel miRNA families. We found that 24 and 12 miRNAs were responsive to powdery mildew infection and heat stress, respectively. We further predicted that 149 target genes were potentially regulated by the novel wheat miRNA. CONCLUSIONS: Our results indicated that diverse set of wheat miRNAs were responsive to powdery mildew infection and heat stress and could function in wheat responses to both biotic and abiotic stresses. PMID- 20573269 TI - De novo characterization of a whitefly transcriptome and analysis of its gene expression during development. AB - BACKGROUND: Whitefly (Bemisia tabaci) causes extensive crop damage throughout the world by feeding directly on plants and by vectoring hundreds of species of begomoviruses. Yet little is understood about its genes involved in development, insecticide resistance, host range plasticity and virus transmission. RESULTS: To facilitate research on whitefly, we present a method for de novo assembly of whitefly transcriptome using short read sequencing technology (Illumina). In a single run, we produced more than 43 million sequencing reads. These reads were assembled into 168,900 unique sequences (mean size = 266 bp) which represent more than 10-fold of all the whitefly sequences deposited in the GenBank (as of March 2010). Based on similarity search with known proteins, these analyses identified 27,290 sequences with a cut-off E-value above 10-5. Assembled sequences were annotated with gene descriptions, gene ontology and clusters of orthologous group terms. In addition, we investigated the transcriptome changes during whitefly development using a tag-based digital gene expression (DGE) system. We obtained a sequencing depth of over 2.5 million tags per sample and identified a large number of genes associated with specific developmental stages and insecticide resistance. CONCLUSION: Our data provides the most comprehensive sequence resource available for whitefly study and demonstrates that the Illumina sequencing allows de novo transcriptome assembly and gene expression analysis in a species lacking genome information. We anticipate that next generation sequencing technologies hold great potential for the study of the transcriptome in other non-model organisms. PMID- 20573270 TI - A semi-supervised learning approach to predict synthetic genetic interactions by combining functional and topological properties of functional gene network. AB - BACKGROUND: Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship between double concurrent perturbation and various higher level phenotypic changes, e.g. those in cells, tissues or organs. Modifier screens, such as synthetic genetic arrays (SGA) can help us to understand the phenotype caused by combined gene mutations. Unfortunately, exhaustive tests on all possible combined mutations in any genome are vulnerable to combinatorial explosion and are infeasible either technically or financially. Therefore, an accurate computational approach to predict genetic interaction is highly desirable, and such methods have the potential of alleviating the bottleneck on experiment design. RESULTS: In this work, we introduce a computational systems biology approach for the accurate prediction of pairwise synthetic genetic interactions (SGI). First, a high-coverage and high-precision functional gene network (FGN) is constructed by integrating protein-protein interaction (PPI), protein complex and gene expression data; then, a graph-based semi-supervised learning (SSL) classifier is utilized to identify SGI, where the topological properties of protein pairs in weighted FGN is used as input features of the classifier. We compare the proposed SSL method with the state-of-the-art supervised classifier, the support vector machines (SVM), on a benchmark dataset in S. cerevisiae to validate our method's ability to distinguish synthetic genetic interactions from non-interaction gene pairs. Experimental results show that the proposed method can accurately predict genetic interactions in S. cerevisiae (with a sensitivity of 92% and specificity of 91%). Noticeably, the SSL method is more efficient than SVM, especially for very small training sets and large test sets. CONCLUSIONS: We developed a graph-based SSL classifier for predicting the SGI. The classifier employs topological properties of weighted FGN as input features and simultaneously employs information induced from labelled and unlabelled data. Our analysis indicates that the topological properties of weighted FGN can be employed to accurately predict SGI. Also, the graph-based SSL method outperforms the traditional standard supervised approach, especially when used with small training sets. The proposed method can alleviate experimental burden of exhaustive test and provide a useful guide for the biologist in narrowing down the candidate gene pairs with SGI. The data and source code implementing the method are available from the website: http://home.ustc.edu.cn/~yzh33108/GeneticInterPred.htm. PMID- 20573271 TI - The role of Qa-2, the functional homolog of HLA-G, in a Behcet's disease-like mouse model induced by the herpes virus simplex. AB - BACKGROUND: It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice. METHODS: RNA interference (RNAi) and vector transfection were employed to manipulate gene expression in vivo in mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively. RESULTS: The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms. CONCLUSIONS: Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice. PMID- 20573272 TI - In-hospital complications after invasive strategy for the management of Non STEMI: women fare as well as men. AB - BACKGROUND: To analyze the in-hospital complication rate in women suffering from non-ST elevation myocardial infarction treated with percutaneous coronary intervention (PCI) compared to men. METHODS: The files of 479 consecutive patients (133 women and 346 men) suffering from a Non STEMI (Non ST-segment elevation myocardial infarction) between the January 1st 2006 and March 21st 2009 were retrospectively analyzed with special attention to every single complication occurring during hospital stay. Data were analyzed using nonparametric tests and are reported as median unless otherwise specified. A p value < .05 was considered significant. RESULTS: As compared to men, women were significantly older (75.8 vs. 65.2 years; p < .005). All cardiovascular risk factors but tobacco and hypertension were similar between the groups: men were noticeably more often smoker (p < .0001) and women more hypertensive (p < .005). No difference was noticed for pre-hospital cardiovascular drug treatment. However women were slightly more severe at entry (more Killip class IV; p = .0023; higher GRACE score for in-hospital death - p = .008 and CRUSADE score for bleeding - p < .0001). All the patients underwent PCI of the infarct-related artery after 24 or 48 hrs post admission without sex-related difference either for timing of PCI or primary success rate. During hospitalization, 130 complications were recorded. Though the event rate was slightly higher in women (30% vs. 26% - p = NS), no single event was significantly gender related. The logistic regression identified age and CRP concentration as the only predictive variables in the whole group. After splitting for genders, these parameters were still predictive of events in men. In women however, CRP was the only one with a borderline p value. CONCLUSIONS: Our study does not support any gender difference for in-hospital adverse events in patients treated invasively for an acute coronary syndrome without ST-segment elevation and elevated troponin. PMID- 20573273 TI - First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia. AB - BACKGROUND: The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed. RESULT: Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue proteome, 76 differentially expressed proteins (p < 0.05; fold change>1.25) were identified between HAD and HIV non-dementia patients, of which 36 protein spots (based on 3D appearance of spots on the images) were chosen for the mass spectrometry analysis. The large majority of identified proteins were represented in the energy metabolic (mitochondria) and signal transduction pathways. Furthermore, over 90% of the protein candidates are common to both HAD and other non-viral neurodegenerative disease, such as Alzheimer's disease. The data was further validated using specific antibodies to 4 proteins (CA2, GS, CKMT and CRMP2) by western blot (WB) in the same samples used for 2D-DIGE, with additional confirmation by immunohistochemitsry (IHC) using frontal lobe tissue from different HAD and HIV+ non-dementia patients. The validation for all 4 antibodies by WB and IHC was in concordance with the DIGE results, lending further credence to the current findings. CONCLUSION: These results suggest not only convergent pathogenetic pathways for the two diseases but also the possibility of increased Alzheimer's disease (AD) susceptibility in HAD patients whose life expectancy has been significantly increased by highly active antiretroviral therapy. PMID- 20573274 TI - Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009. AB - BACKGROUND: Artemisinin derivatives have been used for malaria treatment in Vietnam since 1989. Reported malaria cases have decreased from 1,672,000 with 4,650 deaths in 1991, to 91,635 with 43 deaths in 2006. Current national guidelines recommend artemisinin-based combination therapy (ACT), although artesunate is still available as monotherapy through the private sector. Recent reports suggest that effectiveness of ACT and artesunate monotherapy has declined in western Cambodia. This study examined Plasmodium falciparum resistance patterns over 10 years in southwest Vietnam in infected patients treated with artemisinin compounds. METHODS: The study was conducted in two communes in Phuoc Long district, Binh Phuoc province, 100 km west of the Cambodian border. This was chosen as a likely site for emerging artemisinin resistance because of the high prevalence of P. falciparum malaria, and the length of time that artemisinin had been in use. In vivo and in vitro monitoring of P. falciparum susceptibility to anti-malarial drugs was conducted in 1998, 2001, 2004/5, and 2008/9. Patients with confirmed P. falciparum malaria received therapy with 5 or 7 days of artemisinin (1998 and 2001 respectively) or 7 days of artesunate RESULTS: In the four surveys, 270 patients were recruited and treated. The mean parasite clearance times differed between 1998, 2001 and 2004/5 (1.8, 2.3 and 2.1 days, P < 0.01) but not between 1998 and 2008/2009. The mean parasite clearance times were correlated with parasite density at day 0 (r = 0.4; P < 0.001). Treatment failure rates after PCR adjustment were 13.8%, 2.9%, 1.2%, and 0% respectively. Susceptibility of P. falciparum to artemisinin in in vitro tests was stable during the period, except for a rise in EC90 and EC99 in 2001. CONCLUSIONS: This study showed stable levels of P. falciparum sensitivity to artemisinin compounds in the two sites over a ten-year period. The introduction of ACT in this area in 2003 may have protected against the development of artemisinin resistance. Adherence to the latest WHO and Vietnamese guidelines, which recommend ACT as first-line therapy in all malarious areas, and continued monitoring along the Vietnam-Cambodia border will be essential to prevent the spread of artemisinin resistance in Vietnam. PMID- 20573276 TI - Posttraumatic growth, posttraumatic stress disorder and resilience of motor vehicle accident survivors. AB - BACKGROUND: Although some previous studies have suggested that posttraumatic growth (PTG) is comprised of several factors with different properties, few have examined both the association between PTG and posttraumatic stress disorder (PTSD) and between PTG and resilience, focusing on each of the factors of PTG. This study aimed to examine the hypothesis that some factors of PTG, such as personal strength, relate to resilience, whereas other factors, such as appreciation of life, relate to PTSD symptoms among Japanese motor vehicle accident (MVA) survivors. METHODS: This cross-sectional study was performed with 118 MVA survivors at 18 months post MVA. Data analyzed included self-reporting questionnaire scores on the Posttraumatic Growth Inventory (PTGI), the Impact of Event Scale- Revised (IES-R), and the Sense of Coherence (SOC) scale, which is one of the most widely used scales for measuring resilience. Correlations between scores on the PTGI and IES-R, the PTGI and SOC scale, and the IES-R and SOC scale were established by calculating Spearman's correlation coefficients. RESULTS: PTGI was positively correlated with both SOC and PTSD symptoms, in spite of an inverse relationship between SOC and PTSD symptoms. Relating to others, new possibilities, and personal strength on the PTGI were correlated positively with SOC, and spiritual change and appreciation of life on the PTGI were positively correlated with PTSD symptoms. CONCLUSIONS: Some factors of PTG were positively correlated with resilience, which can be regarded as an outcome of coping success, whereas other factors of PTG were positively correlated with PTSD symptoms, which can be regarded as signifying coping effort in the face of enduring distress. These findings contribute to our understanding of the psychological change experienced by MVA survivors, and to raising clinicians' awareness of the possibility that PTG represents both coping effort coexisting with distress and outcome of coping success. PMID- 20573275 TI - Comparison of low molecular weight glutenin subunits identified by SDS-PAGE, 2 DE, MALDI-TOF-MS and PCR in common wheat. AB - BACKGROUND: Low-molecular-weight glutenin subunits (LMW-GS) play a crucial role in determining end-use quality of common wheat by influencing the viscoelastic properties of dough. Four different methods - sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis (2-DE, IEF x SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and polymerase chain reaction (PCR), were used to characterize the LMW-GS composition in 103 cultivars from 12 countries. RESULTS: At the Glu-A3 locus, all seven alleles could be reliably identified by 2-DE and PCR. However, the alleles Glu A3e and Glu-A3d could not be routinely distinguished from Glu-A3f and Glu-A3g, respectively, based on SDS-PAGE, and the allele Glu-A3a could not be differentiated from Glu-A3c by MALDI-TOF-MS. At the Glu-B3 locus, alleles Glu B3a, Glu-B3b, Glu-B3c, Glu-B3g, Glu-B3h and Glu-B3j could be clearly identified by all four methods, whereas Glu-B3ab, Glu-B3ac, Glu-B3ad could only be identified by the 2-DE method. At the Glu-D3 locus, allelic identification was problematic for the electrophoresis based methods and PCR. MALDI-TOF-MS has the potential to reliably identify the Glu-D3 alleles. CONCLUSIONS: PCR is the simplest, most accurate, lowest cost, and therefore recommended method for identification of Glu-A3 and Glu-B3 alleles in breeding programs. A combination of methods was required to identify certain alleles, and would be especially useful when characterizing new alleles. A standard set of 30 cultivars for use in future studies was chosen to represent all LMW-GS allelic variants in the collection. Among them, Chinese Spring, Opata 85, Seri 82 and Pavon 76 were recommended as a core set for use in SDS-PAGE gels. Glu-D3c and Glu-D3e are the same allele. Two new alleles, namely, Glu-D3m in cultivar Darius, and Glu-D3n in Fengmai 27, were identified by 2-DE. Utilization of the suggested standard cultivar set, seed of which is available from the CIMMYT and INRA Clermont Ferrand germplasm collections, should also promote information sharing in the identification of individual LMW-GS and thus provide useful information for quality improvement in common wheat. PMID- 20573277 TI - Silencing of TESTIN by dense biallelic promoter methylation is the most common molecular event in childhood acute lymphoblastic leukaemia. AB - BACKGROUND: Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia (ALL) and has the potential to contribute to its onset and outcome. However, few reports demonstrate consistent, prevalent and dense promoter methylation, associated with tumour-specific gene silencing. By screening candidate genes, we have detected frequent and dense methylation of the TESTIN (TES) promoter. RESULTS: Bisulfite sequencing showed that 100% of the ALL samples (n = 20) were methylated at the TES promoter, whereas the matched remission (n = 5), normal bone marrow (n = 6) and normal PBL (n = 5) samples were unmethylated. Expression of TES in hyperdiploid, TEL-AML+, BCR-ABL+, and E2A-PBX+ subtypes of B lineage ALL was markedly reduced compared to that in normal bone marrow progenitor cells and in B cells. In addition TES methylation and silencing was demonstrated in nine out of ten independent B ALL propagated as xenografts in NOD/SCID mice. CONCLUSION: In total, 93% of B ALL samples (93 of 100) demonstrated methylation with silencing or reduced expression of the TES gene. Thus, TES is the most frequently methylated and silenced gene yet reported in ALL. TES, a LIM domain-containing tumour suppressor gene and component of the focal adhesion complex, is involved in adhesion, motility, cell-to-cell interactions and cell signalling. Our data implicate TES methylation in ALL and provide additional evidence for the involvement of LIM domain proteins in leukaemogenesis. PMID- 20573278 TI - Trapping mosquitoes using milk products as odour baits in western Kenya. AB - BACKGROUND: Ample evidence has shown that blood seeking mosquitoes locate their hosts by following odours produced by the hosts. Odour baited traps would therefore, provide a solution in controlling diseases spread by mosquitoes. Comparative studies were undertaken to determine the relative efficacies of two odour baits i.e. Limburger cheese and African traditional milk cream in trapping mosquitoes in the field in western Kenya. METHOD: Comparative efficacy studies were carried out in the field using Latin square experimental designs. In the first study, a counterflow geometry (CFG) trap (MM-x model; American Biophysics Corp., USA.) baited with Limburger cheese, man landing catches (MLC), Centres for Disease Control (CDC) light trap and an entry trap were compared. In the second study, three CFG traps baited with either Limburger cheese, African traditional milk cream or with no bait were compared and in the third study four CDC traps baited with either Limburger cheese, African traditional milk cream, light or with no bait were compared. Parameters like species, catch size, abdominal status, parity status and size of the collected mosquitoes were compared. RESULTS: A total of 1,806 mosquitoes were collected (60% An. gambiae s.l and 25% An.funestus, culicines 15%). There was no significant difference in the number of An. funestus trapped by the CFG trap baited with Limburger cheese from those trapped by the MLC (P = 0.351). The Limburger cheese baited CFG trap collected significantly more gravid An. funestus than the MLC (P = 0.022). Furthermore, when the CFG trap baited with Limburger cheese and the CFG trap baited with milk cream were compared, there was no significant difference in the number of An. funestus collected (P = 0.573). The same trend was observed in the comparison of Limburger cheese baited CDC trap and milk cream baited CDC trap. CONCLUSIONS: Limburger cheese and African traditional milk cream have a potential as effective odour baits for sampling/surveillance and as oviposition attractants for the malaria vector, Anopheles funestus. PMID- 20573279 TI - Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice. AB - BACKGROUND: The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. METHODS: The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. RESULTS: HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-alpha in the TIII cells and in melanoma tumors of RET mice. CONCLUSIONS: Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma. PMID- 20573280 TI - In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles. AB - BACKGROUND: RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Delivering sequences of RNAi in vivo remains a problem. The aim of this study was to use JC virus (JCV) virus-like particles (VLPs) as a vector for delivering RNAi in silencing the cytokine gene of IL-10. METHODS: JCV VLPs were generated by recombinant JCV VP1 protein in yeast expression system. DNA fragment containing IL-10 shRNA was packaged into VLPs by osmotic shock. RESULTS: In RAW 264.7 cells, IL-10 shRNA was found to reduce IL-10 expression by 85 to 89%, as compared with VLPs alone. IL-10 shRNA did not cross-react with TNF alpha mRNA or influence the expression of TNF-alpha. In BALB/c mice IL-10 shRNA could reduce 95% of IL-10 secretion. Surprisingly, it also down regulated TNF alpha expression. CONCLUSIONS: We show for the first time that JCV VLPs empty capsids are competent vectors to deliver RNAi and are nontoxic to cells, suggesting that JCV VLPs is an efficient agent to deliver RNAi in both murine macrophage cells and BALB/c mice. This system provides an efficient means for delivering the RNAi for gene therapy purposes. PMID- 20573281 TI - An autocrine sphingosine-1-phosphate signaling loop enhances NF-kappaB-activation and survival. AB - BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a multitude of cellular functions, including cell proliferation, survival, migration and angiogenesis. S1P mediates its effects either by signaling through G protein-coupled receptors (GPCRs) or through an intracellular mode of action. In this study, we have investigated the mechanism behind S1P-induced survival signalling. RESULTS: We found that S1P protected cells from FasL-induced cell death in an NF-kappaB dependent manner. NF-kappaB was activated by extracellular S1P via S1P2 receptors and Gi protein signaling. Our study also demonstrates that extracellular S1P stimulates cells to rapidly produce and secrete additional S1P, which can further amplify the NF-kappaB activation. CONCLUSIONS: We propose a self-amplifying loop of autocrine S1P with capacity to enhance cell survival. The mechanism provides increased understanding of the multifaceted roles of S1P in regulating cell fate during normal development and carcinogenesis. PMID- 20573282 TI - Visioning services for children affected by HIV and AIDS through a family lens. AB - The HIV epidemic continues to place a great burden on children, from loss of parents and income to severe disruptions of their homes and families. Underpinned by the understanding that a healthy family constitutes the foundation for a child's wellbeing, the importance of family-centred care and services for children is increasingly recognized. It is not enough to merely provide antiretrovirals: it is of pivotal importance that treatment and care for children are integrated into the broader context of family-support schemes. However, despite growing evidence of the benefits of family-centred services, reforms in favour of family oriented HIV interventions have been slow to emerge. Treatment, prevention and care interventions often target individuals, and not families and communities.For the first time, this supplement to the Journal of the International AIDS Society brings together in one place the rationale for family centred services for children affected by HIV and AIDS and some of the available evidence for the effectiveness of doing so. We hope this constitutes a beginning of what could be a groundswell of interest in family-centred services for children affected by HIV and AIDS. PMID- 20573283 TI - An introduction to family-centred services for children affected by HIV and AIDS. AB - Family-centred services in the context of HIV/AIDS acknowledge a broad view of a "family system" and ideally include comprehensive treatment and care, community agencies and coordinated case management. The importance of family-centred care for children affected by HIV/AIDS has been recognized for some time. There is a clear confluence of changing social realities and the needs of children in families affected by HIV and AIDS, but a change of paradigm in rendering services to children through families, in both high-prevalence and concentrated epidemic settings, has been slow to emerge.Despite a wide variety of model approaches, interventions, whether medical or psychosocial, still tend to target individuals rather than families. It has become clear that an individualistic approach to children affected by HIV and AIDS leads to confusion and misdirection of the global, national and local response. The almost exclusive focus on orphans, defined initially as a child who had lost one or both parents to AIDS, has occluded appreciation of the broader impact on children exposed to risk in other ways and the impact of the epidemic on families, communities and services for children. In addition, it led to narrowly focused, small-scale social welfare and case management approaches with little impact on government action, global and national policy, integration with health and education interventions, and increased funding.National social protection programmes that strengthen families are now established in several countries hard hit by AIDS, and large-scale pilots are underway in others. These efforts are supported by international and national development agencies, increasingly by governments and, more recently, by UNAIDS and the global AIDS community.There is no doubt that this is the beginning of a road and that there is still a long way to go, including basic research on families, family interventions, and effectiveness and costs of family-centred approaches. It is also clear that many of the institutions that are intended to serve families sometimes fail and frequently even combat non-traditional families. PMID- 20573284 TI - Family-centred approaches to the prevention of mother to child transmission of HIV. AB - BACKGROUND: Prevention of mother to child transmission (PMTCT) programmes have traditionally been narrow in scope, targeting biomedical interventions during the perinatal period, rather than considering HIV as a family disease. This limited focus restricts programmes' effectiveness, and the opportunity to broaden prevention measures has largely been overlooked.Although prevention of vertical transmission is crucial, consideration of the family environment can enhance PMTCT. Family-centred approaches to HIV prevention and care present an important direction for preventing paediatric infections while improving overall family health. This paper reviews available literature on PMTCT programmatic models that have taken a broader or family-centred approach. We describe findings and barriers to the delivery of family-centred PMTCT and identify a number of promising new directions that may achieve more holistic services for children and families. METHODS: Literature on the effectiveness of family-centred PMTCT interventions available via PubMed, EMBASE and PsycINFO were searched from 1990 to the present. Four hundred and three abstracts were generated. These were narrowed to those describing or evaluating PMTCT models that target broader aspects of the family system before, during and/or after delivery of an infant at risk of acquiring HIV infection (N = 14). RESULTS: The most common aspects of family-centred care incorporated by PMTCT studies and programme models included counselling, testing, and provision of antiretroviral treatment for infected pregnant women and their partners. Antiretroviral therapy was also commonly extended to other infected family members. Efforts to involve fathers in family based PMTCT counselling, infant feeding counselling, and general decision making were less common, though promising. Also promising, but rare, were PMTCT programmes that use interventions to enrich family capacity and functioning; these include risk assessments for intimate partner violence, attention to mental health issues, and the integration of early childhood development services. CONCLUSIONS: Despite barriers, numerous opportunities exist to expand PMTCT services to address the health needs of the entire family. Our review of models utilizing these approaches indicates that family-centred prevention measures can be effectively integrated within programmes. However, additional research is needed in order to more thoroughly evaluate their impact on PMTCT, as well as on broader family health outcomes. PMID- 20573285 TI - Lessons learned from family-centred models of treatment for children living with HIV: current approaches and future directions. AB - BACKGROUND: Despite strong global interest in family-centred HIV care models, no reviews exist that detail the current approaches to family-centred care and their impact on the health of children with HIV. A systematic review of family-centred HIV care programmes was conducted in order to describe both programme components and paediatric cohort characteristics. METHODS: We searched online databases, including PubMed and the International AIDS Society abstract database, using systematic criteria. Data were extracted regarding programme setting, staffing, services available and enrolment methods, as well as cohort demographics and paediatric outcomes. RESULTS: The search yielded 25 publications and abstracts describing 22 separate cohorts. These contained between 43 and 657 children, and varied widely in terms of staffing, services provided, enrolment methods and cohort demographics. Data on clinical outcomes was limited, but generally positive. Excellent adherence, retention in care, and low mortality and/or loss to follow up were documented. CONCLUSIONS: The family-centred model of care addresses many needs of infected patients and other household members. Major reported obstacles involved recruiting one or more types of family members into care, early diagnosis and treatment of infected children, preventing mortality during children's first six months of highly active antiretroviral therapy, and staffing and infrastructural limitations. Recommendations include: developing interventions to enrol hard-to-reach populations; identifying high-risk patients at treatment initiation and providing specialized care; and designing and implementing evidence-based care packages. Increased research on family-centred care, and better documentation of interventions and outcomes is also critical. PMID- 20573287 TI - Data availability on men's involvement in families in sub-Saharan Africa to inform family-centred programmes for children affected by HIV and AIDS. AB - The Joint Learning Initiative on Children and AIDS recently recommended that programmes for children affected by HIV and AIDS in sub-Saharan Africa direct more support to families. Interest has grown in including men in such family orientated interventions by researchers, policy makers, and community and non governmental organizations. However, there is a lack of good quality data on men's involvement with children in the diverse settings in sub-Saharan Africa. In addition, limited research has examined their role in providing emotional, material support and protection for HIV- and AIDS-affected children and families.In this paper, we describe the availability of data about men and families, in particular fathers, in ongoing sub-Saharan African surveys and longitudinal population cohorts. We discuss the conceptual and measurement issues associated with data collection on men's involvement in these types of studies. We consider the opportunities for improving the collection of data about men and families in household surveys and population cohorts in order to inform the design and evaluation of family-centred interventions for children affected by HIV and AIDS. PMID- 20573286 TI - Fathers and HIV: considerations for families. AB - BACKGROUND: Fathers are intricately bound up in all aspects of family life. This review examines fathers in the presence of HIV: from desire for a child, through conception issues, to a summary of the knowledge base on fathers within families affected by HIV. METHODS: A mixed-methods approach is used, given the scarcity of literature. A review is provided on paternal and male factors in relation to the desire for a child, HIV testing in pregnancy, fatherhood and conception, fatherhood and drug use, paternal support and disengagement, fatherhood and men who have sex with men (MSM), and paternal effects on child development in the presence of HIV. Literature-based reviews and systematic review techniques are used to access available data Primary data are reported on the issue of parenting for men who have sex with men. RESULTS: Men with HIV desire fatherhood. This is established in studies from numerous countries, although fatherhood desires may be lower for HIV-positive men than HIV-negative men. Couples do not always agree, and in some studies, male desires for a child are greater than those of their female partners. Despite reduced fertility, support and services, many proceed to parenting, whether in seroconcordant or serodiscordant relationships. There is growing knowledge about fertility options to reduce transmission risk to uninfected partners and to offspring.Within the HIV field, there is limited research on fathering and fatherhood desires in a number of difficult-to-reach groups. There are, however, specific considerations for men who have sex with men and those affected by drug use. Conception in the presence of HIV needs to be managed and informed to reduce the risk of infection to partners and children. Further, paternal support plays a role in maternal management. CONCLUSIONS: Strategies to improve HIV testing of fathers are needed. Paternal death has a negative impact on child development and paternal survival is protective. It is important to understand fathers and fathering and to approach childbirth from a family perspective. PMID- 20573288 TI - Children of female sex workers and drug users: a review of vulnerability, resilience and family-centred models of care. AB - BACKGROUND: Injection drug users and female sex workers are two of the populations most at risk for becoming infected with HIV in countries with concentrated epidemics. Many of the adults who fall into these categories are also parents, but little is known about the vulnerabilities faced by their children, their children's sources of resilience, or programmes providing services to these often fragile families. This review synthesizes evidence from disparate sources describing the vulnerabilities and resilience of the children of female sex workers and drug users, and documents some models of care that have been put in place to assist them. REVIEW: A large literature assessing the vulnerability and resilience of children of drug users and alcoholics in developed countries was found. Research on the situation of the children of sex workers is extremely limited. Children of drug users and sex workers can face unique risks, stigma and discrimination, but both child vulnerability and resilience are associated in the drug use literature with the physical and mental health of parents and family context. Family-centred interventions have been implemented in low- and middle-income contexts, but they tend to be small, piecemeal and struggling to meet demand; they are poorly documented, and most have not been formally evaluated. We present preliminary descriptive data from an organization working with pregnant and new mothers who are drug users in Ukraine and from an organization providing services to sex workers and their families in Zambia. CONCLUSIONS: Because parents' drug use or sex work is often illegal and hidden, identifying their children can be difficult and may increase children's vulnerability and marginalization. Researchers and service providers, therefore, need to proceed with caution when attempting to reach these populations, but documentation and evaluation of current programmes should be prioritized. PMID- 20573289 TI - The impact of HIV and high-risk behaviours on the wives of married men who have sex with men and injection drug users: implications for HIV prevention. AB - BACKGROUND: HIV/AIDS in India disproportionately affects women, not by their own risks, but by those of their partners, generally their spouses. We address two marginalized populations at elevated risk of acquiring HIV: women who are married to men who also have sex with men (MSM) and wives of injection drug users (IDUs). METHODS: We used a combination of focus groups (qualitative) and structured surveys (quantitative) to identify the risks that high-risk men pose to their low risk wives and/or sexual partners. Married MSM were identified using respondent driven recruitment in Tamil Nadu, India, and were interviewed by trainer assessors. A sample of wives of injection drug users in Chennai were recruited from men enrolled in a cohort study of the epidemiology of drug use among IDUs in Chennai, and completed a face-to-face survey. Focus groups were held with all groups of study participants, and the outcomes transcribed and analyzed for major themes on family, HIV and issues related to stigma, discrimination and disclosure. RESULTS: Using mixed-methods research, married MSM are shown to not disclose their sexual practices to their wives, whether due to internalized homophobia, fear of stigma and discrimination, personal embarrassment or changing sexual mores. Married MSM in India largely follow the prevailing norm of marriage to the opposite sex and having a child to satisfy social pressures. Male IDUs cannot hide their drug use as easily as married MSM, but they also avoid disclosure. The majority of their wives learn of their drug-using behaviour only after they are married, making them generally helpless to protect themselves. Fear of poverty and negative influences on children were the major impacts associated with continuing drug use. CONCLUSIONS: We propose a research and prevention agenda to address the HIV risks encountered by families of high-risk men in the Indian and other low- and middle-income country contexts. PMID- 20573290 TI - Family-based HIV prevention and intervention services for youth living in poverty affected contexts: the CHAMP model of collaborative, evidence-informed programme development. AB - Family-based interventions with children who are affected by HIV and AIDS are not well established. The Collaborative HIV Prevention and Adolescent Mental Health Program (CHAMP) represents one of the few evidence-based interventions tested in low-income contexts in the US, Caribbean and South Africa. This paper provides a description of the theoretical and empirical bases of the development and implementation of CHAMP in two of these countries, the US and South Africa. In addition, with the advent of increasing numbers of children infected with HIV surviving into adolescence and young adulthood, a CHAMP+ family-based intervention, using the founding principles of CHAMP, has been developed to mitigate the risk influences associated with being HIV positive. PMID- 20573291 TI - Family-centred HIV interventions: lessons from the field of parental depression. AB - Traditionally, HIV prevention focuses on individual behaviours that place one at risk for HIV infection. Less widely regarded as a fundamental public health issue is parental depression and the detrimental effects it exerts on infant and child development, as well as its key contribution to non-fatal burden. Much like many HIV prevention and treatment interventions, programmes for depression focus almost exclusively on individuals and individual behaviour. This paper will use the extensive evidence base from research into parental depression as a model to argue for a family based approach to HIV prevention and treatment. The aim of this will be to make a case for targeting a broader set of behaviours that occur within families when developing and implementing interventions. PMID- 20573292 TI - Intensive cognitive therapy for PTSD: a feasibility study. AB - BACKGROUND: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. METHOD: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. RESULTS: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. CONCLUSIONS: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials. PMID- 20573293 TI - Lymph node central necrosis on computed tomography as predictor of extracapsular spread in metastatic head and neck squamous cell carcinoma: pilot study. AB - OBJECTIVE: This study aimed (1) to investigate the relationship between the presence of lymph node central necrosis, viewed on pre-operative computed tomography imaging, and the occurrence of histopathologically determined metastatic lymph node extracapsular spread and (2) to determine whether a larger scale study would be valuable. MATERIALS AND METHODS: Pre-operative computed tomography scans, surgical records and post-operative histopathological analysis results were reviewed for 19 consecutive neck dissections performed in 17 patients with head and neck squamous cell carcinoma. RESULTS: A total of 20/26 (77 per cent) lymph nodes with central necrosis had extracapsular spread on histopathological analysis. Twenty of 21 (95 per cent) lymph nodes with extracapsular spread had central necrosis on pre-operative computed tomography. Thirty-four of 40 (85 per cent) lymph nodes without extracapsular spread had no evidence of central necrosis on computed tomography. Only three of 12 (25 per cent) patients with lymph node central necrosis identified on pre-operative computed tomography were found to have actual necrosis on final histopathological analysis. CONCLUSIONS: Lymph node central necrosis viewed on pre-operative computed tomography scans is a useful indicator of metastatic lymph node extracapsular spread, with a sensitivity of 95 per cent, a specificity of 85 per cent, a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Lymph node diameter is not a sensitive indicator of extracapsular spread. PMID- 20573294 TI - Recurrent familial malignant carotid body tumour presenting with lymph node metastasis: case report, and review of diagnosis and management of familial carotid body tumours. AB - OBJECTIVE: We report the case of a recurrent familial malignant carotid body tumour presenting with metastasis to local ipsilateral lymph nodes; the rarity of both recurrence combined with nodal spread is emphasised in this article. METHOD: We present a case report, and a review of the world literature concerning the diagnosis and management of carotid body tumours in the familial setting. CASE REPORT: A woman with a family history of succinate dehydrogenase complex subunit B gene mutation presented with right vocal fold palsy. A causative carotid body tumour was excised. Fifteen years later, the patient developed a right-sided swelling in the jugulo-digastric region, together with shooting pains towards her right ear. Imaging revealed right posterior triangle lymphadenopathy. Fine needle aspiration cytology of the node was equivocal. Computed tomography of her neck revealed, in addition, a mass within the right side of the larynx. Excision biopsy of the lymph node demonstrated metastatic paraganglioma. A carotid angiogram revealed a right-sided carotid body tumour. This was embolised prior to neck exploration and excision of the carotid body tumour with en bloc resection of adjacent nodes. Histological analysis confirmed the presence of lymph nodes containing metastatic paraganglioma. CONCLUSION: This case report demonstrates the need for extra vigilance to enable early disease detection in the familial setting of carotid body tumour, in order to reduce the surgical morbidity associated with disease progression. In addition, our report highlights the atypical aspects of presentation in the familial setting, together with the difficulty and lack of standardisation regarding monitoring of the disease. PMID- 20573295 TI - Expression of phosphatidylserine-specific phospholipase A(1) mRNA in human THP-1 derived macrophages. AB - The expression of phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) is most upregulated in the genes of peripheral blood cells from chronic rejection model rats bearing long-term surviving cardiac allografts. The expression profile of PS-PLA(1) in peripheral blood cells responsible for the immune response may indicate a possible biological marker for rejection episodes. In this study, PS PLA(1) mRNA expression was examined in human THP-1-derived macrophages. The effects of several immunosuppressive agents on this expression were also examined in in vitro experiments. A real-time RT-PCR analysis revealed that PS-PLA(1) mRNA expression was found in human THP-1-derived macrophages. This expression was enhanced in the cells stimulated with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. Other TLR ligands (TLR2, 3, 5, 7, and 9) did not show a significant induction of PS-PLA(1) mRNA. The time course of the mRNA expression profiles was different between PS-PLA(1) and tumor necrosis factor-alpha (TNF alpha), which showed a maximal expression at 12 and 1 h after LPS stimulation, respectively. Among the observed immunosuppressive agents, corticosteroids, prednisolone, 6alpha-methylprednisolone, dexamethasone, and beclomethasone inhibited PS-PLA(1) expression with half-maximal inhibitory concentrations less than 3.0 nM, while methotrexate, cyclosporine A, tacrolimus, 6-mercaptopurine, and mycophenoic acid showed either a weak or moderate inhibition. These results suggest that the expression of PS-PLA(1) mRNA in THP-1-derived macrophages is activated via TLR4 and it is inhibited by corticosteroids, which are used at high dosages to suppress chronic allograft rejection. PMID- 20573296 TI - Improved yield and functional parameters of rat pancreas islets isolated under intramuscular anesthesia. AB - Intraperitoneal (IP) anesthesia is commonly used for laboratory animal experiments including rat islet isolation. However, the direct effects of anesthetics on pancreatic islets have been neglected. This study compared the islet function and recovery yield from rats that were anesthetized using IP and intramuscular (IM) injection. In addition, the lag time required to lose deep pain was measured in the following anesthetics combinations. Lewis rats were anesthetized using ketamine and xylazine (K/X) or zoletil and xylazine (Z/X). A glucose challenge test was performed on each group of prepared islets. The effect of the anesthetic agents (e.g., ketamine, zoletil, xylazine alone, and the combination of K/X and Z/X) on cell lines (rat insulinoma; RIN-5F) was investigated by determining their effect on the cell viability, the amount of insulin, and insulin mRNA expression levels of RIN-5F. The time needed for deep anesthesia in IM anesthesia was significantly shortened in comparison to IP [K/X (IM: 313 +/- 66 s, IP: 371 +/- 84 s) and Z/X (IM: 206 +/- 76 s, IP: 245 +/- 92 s)]. In addition, number of isolated islet yield by IM anesthesia was significantly improved [K/X (IM: 1530 +/- 242, IP: 1245 +/- 149) and Z/X (IM: 1136 +/- 226, IP: 511 +/- 154)]. The functions of fresh islets, indicated by the stimulation index, acquired under IM anesthesia was better preserved than that of IP. The viability and the insulin secretion of RIN-5F were decreased at 24 and 48 h. Insulin gene expression levels were decreased at 24 h as well. Anesthetics may be absorbed through the pancreas surface to the islets and have a direct effect, resulting in islet exposure and deterioration during isolation. In conclusion, for rodent islet isolation, IM anesthesia is simpler and safer in comparison to IP anesthesia. PMID- 20573297 TI - Prevention of graft-versus-host diseases by in vivo supCD28mAb-expanded antigen specific nTreg cells. AB - Naturally occurring CD4(+)CD25(+) Treg cells (nTregs) can be exploited to establish an immunologic tolerance to non-self-antigens. The in vivo administration of a single superagonistic CD28-specific monoclonal antibody (supCD28mAb) to naive rat preferentially expanded the nTregs, which induced a potent inhibition of lethality of the graft-versus-host (GvH) diseases. The appearance of increased Foxp3 molecules was accompanied with a polarization towards a Th2 cytokine profile with a decreased production of IFN-gamma and increased production of IL-4 and IL-10 in the serum of the antibody-treated rat. The peripheral Foxp3 nTregs are decreased in acute GvHD, while supCD28mAb administration showed that nTregs were preferentially proliferating in vivo, thus resulting in the significant prevention of the GvH disease. Furthermore, antigen specific nTregs could suppress conventional T-cell proliferation stimulated with alloantigen in vitro. Taken together, our findings demonstrate that the potent regulatory functions of the Tregs for the treatment of GvHD are antigen specific. These data also provide evidence that GvHD is associated with decrease of Tregs in the periphery of the host. The determination of the Foxp3 Tregs can be a helpful tool to discriminate GvHD severity and lethality after allogeneic stem cell transplantation. PMID- 20573298 TI - Bone repair using a hybrid scaffold of self-assembling peptide PuraMatrix and polyetheretherketone cage in rats. AB - Self-assembling peptide scaffold (SAPS) is well known to have very good bone conduction properties. However, the intensity of SAPS is too weak to actually use it for a clinical bone regeneration. Therefore, we have produced a hybrid scaffold system that involves fabricating a cage from polyetheretherketone (PEEK) that has high intensity, filling the interior of this cage with SAPS, and then transplanted this hybrid scaffold to bone defects in rat femurs. After 28 days, soft X-ray radiographs and histological assessment revealed that good new bone formation was clearly observed in the defects transplanted the PEEK cage with SAPS, but not in the PEEK cage only. The PEEK cage maintained a form and osteoconduction ability of internal SAPS, and SAPS promoted bone formation inside the PEEK; therefore, each was in charge of intensity and bone regeneration separately. The present study suggests that hybrid scaffolds made from PEEK cages and SAPS can be useful tools for the regeneration of load-bearing bones, based on the idea that it should be possible to develop ideal bone filler materials by combining the strength of artificial bone with the bone regeneration and bone conduction properties of SAPS. PMID- 20573299 TI - Treatment of acute liver failure in mice by hepatocyte xenotransplantation. AB - Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell-cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival. PMID- 20573301 TI - Engineering liver tissues under the kidney capsule site provides therapeutic effects to hemophilia B mice. AB - Recent advances in liver tissue engineering have encouraged further investigation into the evaluation of therapeutic benefits based on animal disease models. In the present study, liver tissues were engineered in coagulation factor IX knockout (FIX-KO) mice, a mouse model of hemophilia B, to determine if the tissue engineering approach would provide therapeutic benefits. Primary hepatocytes were isolated from the liver of wild-type mice and suspended in a mixture of culture medium and extracellular matrix components. The hepatocyte suspension was injected into the space under the bilateral kidney capsules of the FIX-KO mice to engineer liver tissues. The plasma FIX activities (FIX:C) of the untreated FIX-KO mice were undetectable at any time point. In contrast, the liver tissue engineered FIX-KO mice achieved 1.5-2.5% of plasma FIX activities (FIX:C) and this elevated FIX:C level persisted throughout the 90 day experimental period. Significant FIX mRNA expression levels were found in the engineered liver tissues at levels similar to the wild-type livers. The present study demonstrates that liver tissue engineering could provide therapeutic benefits in the treatment of hemophilia B. PMID- 20573302 TI - Brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets. AB - Tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we focused on the influence of brain death (BD) on TF and MCP-1 expression in the pancreatic tissues and isolated islets using a rodent model. TF and MCP-1 mRNA levels in the pancreatic tissues were similar between the BD and the control group. However, TF and MCP-1 mRNA in the fresh islets of the BD group were significantly higher than that of the control group (p < 0.01). BD may thus be suggested to be of great importance as an initiator of TF and MCP-1 induction in the isolated islets. Furthermore, the upregulation of crucial inflammatory mediators induced by BD could be exacerbated by warm ischemic damage during digestion procedures. In the present study, the islet yield and purity were affected by BD. However, almost no influences were observed with respect to islet viability, indicating that the expression of inflammatory mediators rather than islet viability is more susceptible to BD. According to the change in time course of TF and MCP-1 expression in the isolated islets, the selected time point for islet infusion in current clinical islet transplantation was thus shown to be at its worst level, at least with respect to the damage caused by BD and ischemic stress. In conclusion, BD in combination with warm ischemic stress during isolation procedures induces a high expression of TF and MCP-1 in the isolated islets. In order to reduce the expression of crucial inflammatory mediators in the islet grafts, the management of the pancreas from brain-dead donors with early anti inflammatory treatments is thus warranted. PMID- 20573303 TI - Engineering of an hepatic organoid to develop liver assist devices. AB - Cell-based technologies to support/restore liver function represent one of the most promising opportunities in the treatment of acute liver failure. However, the understanding of the constituent cell types that interact to achieve liver specific structure and function has not been achieved in the development of liver assist devices (LADs). Here we show that hepatocytes migrated toward and adhered and formed sinusoids-like structures in conjunction with liver nonparenchymal cells, and that this liver organoid formed sophisticated tissue after 7 days in an implanted LAD in rodents. Hepatocytes only or in combination with human nonparenchymal liver cell lines (endothelial, cholangiocytes, and stellate cells) were cultured in Matrigel. Ultrastructural analysis showed that the hepatocyte decorated endothelial vascular structures resemble in vivo sinusoids containing plate-like structures, bile canaliculi, and lumen. The sinusoid-like structures retained albumin secretion and drug metabolism capabilities. In addition, LADs containing cocultures of human liver nonparenchymal cells were transplanted in animals for a week; the liver tissue formed sophisticated structures resembling the liver. These results demonstrate the importance of nonparenchymal cells in the cellular composition of LADs. The novelty of the culture's sinusoid-like organization and function strongly support the integration of liver nonparenchymal units into hepatocyte coculture-based LADs as a potential destination therapy for liver failure. PMID- 20573304 TI - Human immune reactivity against liver sinusoidal endothelial cells from GalTalpha(1,3)GalT-deficient pigs. AB - Elimination of galactose-alpha(1,3)galactose (Gal) expression in pig organs has been previously shown to prevent hyperacute xenograft rejection. However, naturally present antibodies to non-Gal epitopes activate endothelial cells, leading to acute humoral xenograft rejection. Still, it is unknown whether xenogeneic pig liver sinusoidal endothelial cells (LSECs) from alpha(1,3)galactosyltransferase (GalT)-deficient pigs are damaged by antibody and complement-mediated mechanisms. The present study examined the xeno-antibody response of LSECs from GalT-deficient and wild pigs. Isolated LSEC from wild-type and GalT pigs were expose to human and baboon sera; IgM and IgG binding was analyzed by flow cytometry. Complement activation (C3a and CH50) was quantified in vitro from serum-exposed LSEC cultures using Enzyme-Linked ImmunoSorbent assay (ELISA). Levels of complement-activated cytotoxicity (CAC) were also determined by a fluorescent Live-Dead Assay and by the quantification of LDH release. IgM binding to GalT knockout (KO) LSECs was significantly lower (80% human and 87% baboon) compare to wild-type pig LSEC. IgG binding was low in all groups. Moreover, complement activation (C3a and CH50) levels released following exposure to human or baboon sera were importantly reduced (42% human and 52% baboon), CAC in GalT KO LSECs was reduced by 60% in human serum and by 72% in baboon serum when compared to wild-type LSECs, and LDH release levels were reduced by 37% and 57%, respectively. LSECs from GalT KO pigs exhibit a significant protection to humoral-induced cell damage compared to LSECs from wild pigs when exposed to human serum. Although insufficient to inhibit xenogeneic reactivity completely, transgenic GalT KO expression on pig livers might contribute to a successful application of clinical xenotransplantation in combination with other protective strategies. PMID- 20573305 TI - Bone marrow mesenchymal stromal cells attenuate organ injury induced by LPS and burn. AB - Bone marrow mesenchymal stromal cells (MSCs) suppress immune cell responses and have beneficial effects in various inflammatory-related immune disorders. A therapeutic modality for systemic inflammation and its consequences is not available yet. Thus, this work investigates the therapeutic effects of MSCs in injury models induced by lipopolysaccharide (LPS) or burn. Gene expression was analyzed in MSCs when exposed to inflammatory serum from injured animals and it showed remarkable alterations compared to normal culture. In addition, injured animals were transplanted intramuscularly with MSCs. Forty-eight hours after cell transplantation, kidney, lung, and liver were analyzed for infiltration of inflammatory cells and TUNEL-expressing cells. Results showed that MSCs attenuate injury by reducing the infiltration of inflammatory cells in various target organs and by reducing cell death. These data suggest that MSCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for systemic inflammatory-based disorders. PMID- 20573306 TI - Glutamatergic excitation and GABA release from a transplantable cell line. AB - The cell line M213-2O CL-4 was derived from cell line M213-2O and further modified to express human glutamate decarboxylase (hGAD-67), the enzyme that synthesizes GABA. Brain transplants of this cell line in animal models of epilepsy have been shown to modulate seizures. However, the mechanisms that underlie such actions are unknown. The purpose of the present study was to characterize this cell line and its responsiveness to several depolarizing conditions, in order to better understand how these cells exert their effects. Intracellular GABA levels were 34-fold higher and GAD activity was 16-fold higher in clone M213-2O CL-4 than in M213-2O. Both cell lines could take up [3H]GABA in vitro, and this uptake was prevented by nipecotic acid. By combining GABA release measurements and calcium imaging in vitro, we found that high extracellular K(+), zero Mg(2+), or glutamate activated M213-2O CL-4 cells and resulted in GABA release. The response to glutamate appeared to be mediated by AMPA/NMDA-like receptors. High KCl-induced GABA release was prevented when a Ca(2+)-free Krebs solution was used, suggesting an exocytotic-like mechanism. These results indicate that the cell line M213-2O CL-4 synthesizes, releases, and takes up GABA in vitro, and can be activated by depolarizing stimuli. PMID- 20573307 TI - Treatment of ocular surface injuries by limbal and mesenchymal stem cells growing on nanofiber scaffolds. AB - Stem cell (SC) therapy represents a promising approach to treat a wide variety of injuries, inherited diseases, or acquired SC deficiencies. One of the major problems associated with SC therapy remains the absence of a suitable matrix for SC growth and transfer. We describe here the growth and metabolic characteristics of mouse limbal stem cells (LSCs) and mesenchymal stem cells (MSCs) growing on 3D nanofiber scaffolds fabricated from polyamide 6/12 (PA6/12). The nanofibers were prepared by the original needleless electrospun Nanospider technology, which enables to create nanofibers of defined diameter, porosity, and a basis weight. Copolymer PA6/12 was selected on the basis of the stability of its nanofibers in aqueous solutions, its biocompatibility, and its superior properties as a matrix for the growth of LSCs, MSCs, and corneal epithelial and endothelial cell lines. The morphology, growth properties, and viability of cells grown on PA6/12 nanofibers were comparable with those grown on plastic. LSCs labeled with the fluorescent dye PKH26 and grown on PA6/12 nanofibers were transferred onto the damaged ocular surface, where their seeding and survival were monitored. Cotransfer of LSCs with MSCs, which have immunosuppressive properties, significantly inhibited local inflammatory reactions and supported the healing process. The results thus show that nanofibers prepared from copolymer PA6/12 represent a convenient scaffold for growth of LSCs and MSCs and transfer to treat SC deficiencies and various ocular surface injuries. PMID- 20573308 TI - Colonic diverticulitis in the neck: a late complication of laryngopharyngectomy surgery. AB - We report a case of diverticulitis affecting a colonic segment used as an interposition graft following laryngopharyngectomy. The patient presented as an emergency to our department with a history of a red, swollen and painful neck. She had undergone laryngopharyngectomy for laryngeal cancer in 1967. Computed tomography imaging revealed several diverticula in the colonic graft and associated abscess formation. The patient's clinical condition behaved similarly to that of conventional colonic diverticulitis. The difficulties in reaching a definite diagnosis and management of this unusual complication following laryngopharyngectomy are discussed. PMID- 20573309 TI - An unusual case of chronic anal pain--a pin in the bum? AB - We report the case of a 70-year-old woman who had previously undergone anterior resection in 2001 for a diverticular stricture. Bleeding from pelvic veins intra operatively necessitated the use of two thumbtacks to aid haemostasis. Over the next 7 years, she presented repeatedly with anal pain, bleeding and mucus discharge per rectum. Multiple lower gastrointestinal endoscopies failed to make a definitive diagnosis until a single thumbtack was found eroding through the rectal mucosa. This was removed and she has been subsequently asymptomatic. This condition was clearly difficult to diagnose and requires a high index of suspicion in those patients who have previously undergone pelvic surgery. PMID- 20573310 TI - Ileocaecal intussusception secondary to metastatic phyllodes tumour of the breast. AB - A patient with phyllodes tumour of the breast is discussed. During follow-up, she presented with intestinal obstruction caused by ileocaecal intussusception. The cause of the intussusception was metastatic phyllodes tumour, which is a unique presentation. PMID- 20573311 TI - Short course pre-operative ferrous sulphate supplementation--is it worthwhile in patients with colorectal cancer? AB - INTRODUCTION: Pre-operative anaemia is well recognised in patients presenting with colorectal cancer (CRC). While the benefits of long-term FeSO4 supplementation on Fe deficiency anaemia are well established, it is not known if short-course supplementation (2-3 weeks) impacts significantly on pre-operative haemoglobin (Hb) levels. This study examines the impact of short-term, oral FeSO4 supplementation on patients undergoing surgery for CRC. PATIENTS AND METHODS: All patients with CRC presenting to a single surgeon were included. At diagnosis, baseline Hb and blood film were checked on all patients who then received 200 mg tds of FeSO4. Haemoglobin was rechecked pre-operatively and daily postoperatively. Patients requiring pre-operative blood transfusions were excluded from analysis. RESULTS: Between 1 January 2004 and 31 December 2006, 117 patients were identified, 14 of whom were excluded. Patients received a median of 39 days' treatment with FeSO4. Fifty-eight (56.3%) patients were anaemic at presentation gaining a mean of 1.73 g/dl (P<0.001) from short-course FeSO4 supplementation. Right-sided tumours (lower mean Hb at presentation; P=0.008) responded more to FeSO4 when compared to left-sided tumours (P<0.017). Increase in Hb was unrelated to pathological stage. The transfusion rate for all curative resections was 0.69 units/patient. For the historical cohort (patients undergoing curative resection between 1 January 2001 and 31 December 2003), the mean transfusion rate fell from 1.69 units/patient. CONCLUSIONS: Routine short-course supplementation with iron offers improved pre-operative Hb prior to surgery in CRC, especially in right-sided lesions and those with presenting anaemia. PMID- 20573312 TI - Traumatic arterial spasm causing transient limb ischaemia: a genuine clinical entity. AB - Traumatic arterial spasm is a phenomenon that has long been questioned by clinicians. Indeed, some would argue that surgical exploration is mandatory whenever there are signs of distal ischaemia following limb trauma. We present a case of angiographically demonstrated tibial artery spasm following gunshot injury. Exploration was unnecessary and distal perfusion was reestablished spontaneously. This case demonstrates the existence of traumatic arterial spasm as a genuine clinical entity and suggests that immediate surgical exploration may not be necessary in all cases. PMID- 20573313 TI - Neuroendocrine carcinoma arising within a retroperitoneal mature teratoma. AB - We discuss an unusual case of a large cystic mass arising in the left upper quadrant of a 48-year-old woman. Radiological investigations could not confirm the origin or the nature of the mass. A laparatomy revealed a large retroperitoneal cystic mass sandwiched between the left adrenal, spleen and the gastro-oesophageal junction. Histological analysis confirmed a mature teratoma of the retroperitoneum with neuroendocrine carcinoma arising within it. To our knowledge this is only the second reported case of its kind. PMID- 20573314 TI - Structure of water in the vicinity of amphoteric polymers as revealed by vibrational spectroscopy. AB - The water incorporated in a thin film of amphoteric terpolymers composed of various ratios of methacrylic acid (MA), N-[3 (dimethylamino)propyl]methacrylamide (DMAPMA) and n-butyl methacrylate was analyzed using the band shapes of the O-H stretching in the infrared spectra. At an early stage of sorption of water into the polymer film, the O-H stretching band for the water incorporated in the film with comparative contents of MA and DMAPMA residues was similar to that for bulk water. These results clearly indicate that the amphoteric polymers with comparative contents of cationic and anionic groups do not significantly disturb the hydrogen-bonded network structure of water, probably due to the counteraction of the electrostatic hydration effect by the proximity between the anionic and cationic side groups. The number of platelets adhered to the film with comparative contents of MA and DMAPMA residues was relatively the smallest among the examined terpolymer films, which suggested a correlation between the mildness of the charge-balanced polymeric materials to the structure of incorporated water and their blood-compatibilities. In addition, the structure and hydrogen bonding of water in an aqueous solution of co-polymers composed of various ratios of MA and DMAPMA or [3 (methacryloylamino)propyl]trimethylammonium chloride (MAPTAC) were also analyzed using the contours of the O-H stretching in the polarized Raman spectra. The number of hydrogen bonds disrupted due to the presence of one monomer residue (N(corr) value) for PolyMA was largely positive, and with an increase in the content of the DMAPMA or MAPTAC residues, the N(corr) value became smaller, and after passing a minimum (which was still slightly positive) at a roughly equivalent molar ratio, the N(corr) value increased again. This is in a significant contrast with the largely positive N(corr) values for the homo polymers (PolyMA, PolyDMAPMA and PolyMAPTAC), and other ordinary polyelectrolytes. The effect of the charge-balanced co-polymer on the hydrogen bonded network structure of vicinal water observed by Raman spectroscopy was in accordance with that of the charge-balanced terpolymer film observed by infrared spectroscopy. PMID- 20573315 TI - Studies on a novel multi-sensitive hydrogel: influence of the biomimetic phosphorylcholine end-groups on the PEO-PPO-PEO tri-block co-polymers. AB - In the present study, a biomimetic phosphorylcholine group was employed in the end-capping modification of PEO-PPO-PEO tri-block co-polymers (Pluronic((r))). The structures of the resulting materials were characterized by (1)H-NMR and GPC. The effects of the additional phosphorylcholine end-groups to the thermo sensitive sol-gel transition behaviors of the aqueous solutions of the resulting polymers were studied by rheology test in neutral (0.1 M NaCl) aqueous solutions and in acidic solutions (pH 3). It was found that the phosphorylcholine-end capped Pluronic hydrogels still kept their thermo-sensitive mechanical properties with a slight change on the sol-gel transition behaviors. The phosphorylcholine modified Pluronics exhibited a response to the change of the pH value, which made this kind of material a multi-sensitive hydrogel system. Also, the resulting polymers showed improved hemocompatibilities in the blood coagulation test using full human blood. PMID- 20573316 TI - A comparative evaluation of disulfide-linked and hydrophobically-modified PEI for plasmid delivery. AB - Non-viral gene therapy has become an important approach for treatment of hereditary and acquired diseases as a result of better understanding of molecular mechanisms involved in disease development. To design more effective gene carriers, plasmid DNA (pDNA) delivery to 293T cells was investigated by using two types of polymeric carriers; polymer constructed with disulfide (-S-S-) linkages and polymers modified with hydrophobic moieties. The base polymer used for this study was 2-kDa poly(ethylene imine) (PEI2), a relatively cell-compatible but ineffective gene carrier. The -S-S- linking was achieved via Michael addition reaction using cystamine bisacrylamide (CBA), whereas hydrophobic modification by N-acylation of PEI2 amines with palmitoyl chloride (PA). The cytotoxicity of the polymers was found to be lower than that of the 25-kDa branched PEI, but both types of modifications increased the toxicity of PEI2 to some extent. The polymers were able to form polyplexes with pDNA with variable hydrodynamic sizes (130-600 nm) and zeta-potential (3.6-20.9 mV). Based on the expression of the reporter gene Enhanced Green Fluorescent Protein (EGFP), disulfide linking significantly increased the efficiency of native PEI2, which was not effective on its own. The PA-modified PEI2 was also effective for gene delivery, but disulfide linkage of this polymer did not increase its efficiency any further. Our results showed that hydrophobic modification of 2-kDa PEI significantly improved its transfection efficiency but improvements in transfection efficiency as a result of disulfide linking was dependent on the nature of the polymeric building blocks. PMID- 20573317 TI - Peripheral nerve regeneration and electrophysiological recovery with CIP-treated allogeneic acellular nerves. AB - Acellular nerve grafts are a desirable alternative to autografts, both because the source of acellular nerves is potentially unlimited and because they have the same matrix structure as natural nerves, which would facilitate axon growth from the defective nerve stump. Although some acellular nerves have been developed, most of them were studied in isogenic transplantation models and evaluated only by histological observation. In the present study, novel allogeneic acellular nerves prepared using the cold isostatic pressuring (CIP) method were developed and assessed as a potential substitute for autografts. The host immune response to acellular nerves and fresh nerves was analyzed using Lewis rats as donors and SD rats as recipients, which is the allogeneic transplantation model, by subcutaneous implantation for one month. In addition, sciatic nerve transplantation into a 10-mm nerve gap was carried out using the same model, and the axonal growth in acellular nerve transplantation was evaluated histologically and electrophysiologically, and compared with that of axons in the autograft transplant area. The subcutaneously implanted acellular nerves contained more macrophages and less vasculature than the allogeneic fresh nerves. In spite of these results of the subcutaneous implantation, Schwann cell infiltration in the graft transplanted into the sciatic nerve gap was observed after the short-term transplantation. The myogenic potential, which was measured as an index of electrophysiological function in acellular nerve transplantation, was also recovered in the long-term transplantation. Our results indicate that the acellular nerves developed herein have the potential to support nerve regeneration and might be useful as an alternative to autografts. PMID- 20573318 TI - On the role of water molecules in the interface between biological systems and polymers. AB - The excellent biocompatibility of PMEA was ascribed by Tanaka to the predominant population of intermediate water in the hydrated polymer matrix. The intermediate water concept was examined using the 'nano-plate model' on the basis of new results (by Morita) of a time-resolved IR study on the water sorption process into PMEA. The examination showed that the image picture proposed by Tanaka concerning the role of intermediate water was in consistent with experimental results so far obtained. Morita showed that the intermediate water exhibited a strong peak at 3400 cm(-1) in its IR spectrum. Water sorption profiles of MMA, PEG and PMVE were found to be similar to that of PMEA. It was shown that the biocompatibility of these polymers could be explained by the intermediate water concept. It was also pointed out that PVP and PDMAA have a considerable amount of intermediate water under appropriate circumstances. The PHEMA-water system showed neither clear peak for cold crystallization in DSC chart, nor the strong peak at 3400 cm(-1) in its IR spectrum, because the PHEMA system did not contain enough intermediate water to show similar behavior to PMEA. The hydrated PHEMA matrix contains a stable network structure of water molecules including the nodes of OH groups of its side-chains. In the stable network system, most water molecules should be hydrogen bonded strongly to form non-freezing water, but not intermediate water. The inferior biocompatibility of PHEMA was ascribed to the stable network structure of water molecules. Some of the PHEMA co-polymers, on the other hand, were found to have highly improved biocompatibility. Mechanism for the improvement was discussed in terms of loosening the network structure, which could be brought about by introducing ionic groups or branching to the polymer chains through co-polymerization with appropriate 'key monomers'. The mobility of polymer chains, as well as the population of three kinds of water in polysaccharide molecules in aqueous medium could change in response to their chemical structure such as nature of ionic groups, the degree of branching, etc. Polysaccharides located at the utmost-outer layer of blood cells probably possess a loosened network structure to form soft biological surface where intermediate water predominates. Cellulose, on the other hand, has a common feature with PHEMA in the sense of predominance of the non-freezing water in its hydrated system. Note: The word 'biocompatibility' is used in general as the term evaluating properties of materials which do not cause adverse effect when the materials come into contact with living organisms, such as proteins, biological cells and tissues. This review paper primarily deals with 'biocompatibility' of polymer materials against various biological elements in blood flow system. PMID- 20573319 TI - 2H-NMR and 13C-NMR study of the hydration behavior of poly(2-methoxyethyl acrylate), poly(2-hydroxyethyl methacrylate) and poly(tetrahydrofurfuryl acrylate) in relation to their blood compatibility as biomaterials. AB - We recorded 2H-NMR spectra of (deuterated) water in the presence of poly(2 methoxyethyl acrylate) (PMEA), poly(2-hydroxyethyl methacrylate) (PHMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA). The observed 2H-NMR peak intensities varied substantially with water content and temperature, depending upon either strong binding to polymer surface or suppressed peaks due to freezing. Indeed, 2H NMR signals in the presence of PHEMA were strongly dependent upon its water content, while those of hydrated PMEA and PTHFA remained unchanged even at -30 degrees C and -20 degrees C. The latter were considerably broadened at -50 degrees C and -30 degrees C, respectively, due to freezing water from the super cooled state. As a result, the states of the water molecules in PMEA and PTHFA can be classified into three types; free, freezing bound and non-freezing water molecules. The states of the water in PHEMA depend on the water content, and the water can be classified into two types, free and non-freezing water, which exhibit rapid fluctuation and restricted mobility because of the presence of macromolecules, respectively. A kind of freezing bound water, however, should exist in PHEMA. This is also consistent with the substantially decreased 2H spin lattice relaxation times of hydrated PHEMA as compared with those of PMEA or PTHFA. It is also interesting to note that the flexibility of bound water or polymer (PMEA > PTHFA > PHEMA) is related to a characteristic parameter for biocompatibility such as the production of TAT (thrombin-antithrombin III complex) as a marker of activation of the coagulation system. Therefore, it is naturally recognized that such differential polymer dynamics might be responsible for concomitant changes in structure and dynamics of surrounding water molecules in the vicinity of constituent polymer network. PMID- 20573320 TI - Synthesis and characterization of CREKA-targeted polymers for the disruption of fibrin gel matrix propagation. AB - Recently, efforts to control the propagation of the fibrin gel matrix (FGM) are under investigation as a means of limiting the formation of post-surgical adhesions (PSAs). A series of polymeric biomaterials based on block co-polymers of methacrylic acid (MA) and methoxypolyethylene glycol methacrylate (PEGMA) have been synthesized and characterized in order to study the impact of molecular architecture on the performance of these materials in suppressing FGM development. A robust synthetic strategy has been developed to facilitate the well controlled variation of numerous structural properties, including the relative size of each polymer block, the total polymer length, and the length of poly(ethylene glycol) (PEG) chain length, and to incorporate the fibrin-targeting pentapeptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA). Preliminary investigations, based on quartz crystal microgravimetry (QCM), indicate the importance of molecular architecture in modulating the FGM propagation from model surfaces. PMID- 20573321 TI - Water-stable electrospun zein fibers for potential drug delivery. AB - This paper reports the development of electrospun zein fibers with improved water stability and tensile strength for potential drug delivery. The low morphological stability in aqueous environment and poor mechanical properties in dry and wet states have restricted the applications of electrospun protein materials, though these materials possess a unique structure, special adsorption properties, biocompatibility and biodegradability. In this study, the electrospun zein fibers were modified by non-toxic citric acid crosslinking catalyzed by NaOH. An up to 183% enhancement in dry tensile strength and an up to 448% improvement in wet tensile strength were generated. The cross-linked fibers were able to maintain their fibrous structure for 15 days in phosphate-buffered saline at 37 degrees C. Moreover, those cross-linked electrospun zein fibers showed a potential in controlled drug delivery with a 58% drug-loading efficiency and a sustained profile drug release in artificial gastric juice. PMID- 20573322 TI - Treatment-resistant depression in Hispanic patients. AB - About one-third of patients treated with antidepressants do not respond to initial treatment, and Spanish-speaking Hispanic patients with major depression may exhibit a worse response to initial medication than English-speaking patients. Patients and clinicians should be resolute and patient as different regimens are tried throughout the course of treatment. Other options include electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, and the medicinal food L-methylfolate. PMID- 20573323 TI - Psychotherapy for late-life depression. AB - Few data on treating geriatric patients with depression are available. In 2001, a panel of experts reached consensus on preferred treatment strategies for older adults with depression, and guidelines were published to aid clinicians in treating these patients. This activity reviews the recommendations and provides updated evidence on the use of psychotherapy in the treatment of older adults with depression, including the development of a problem-solving therapy designed to increase patient functioning and address symptoms seen in depressed patients with executive dysfunction. PMID- 20573324 TI - Diagnostic features, prevalence, and impact of bipolar disorder. AB - Bipolar disorder shares depressive symptoms with unipolar major depressive disorder but is defined by episodes of mania or hypomania. Bipolar disorder in its broadest sense has a community lifetime prevalence of 4% and is a severely impairing illness that impacts several aspects of patients' lives. Race, ethnicity, and gender have no effect on prevalence rates, but women are more likely to experience rapid cycling, mixed states, depressive episodes, and bipolar II disorder than men. Patients with bipolar disorder have high rates of disability and higher rates of mortality than individuals without bipolar disorder. Natural causes such as cardiovascular disease and diabetes, as well as suicide and other "unnatural" causes are key contributors to the high mortality rate. The costs associated with bipolar disorder include not only the direct costs of treatment, but also the much greater indirect costs of decreased productivity, excess unemployment, and excess mortality. PMID- 20573325 TI - Complementary and alternative medicine in psychiatry. PMID- 20573326 TI - Complementary and alternative medicine in major depressive disorder: the American Psychiatric Association Task Force report. AB - OBJECTIVE: To review selected complementary and alternative medicine (CAM) treatments for major depressive disorder (MDD). PARTICIPANTS: Authors of this report were invited participants in the American Psychiatric Association's Task Force on Complementary and Alternative Medicine. EVIDENCE: The group reviewed the literature on individual CAM treatments for MDD, methodological considerations, and future directions for CAM in psychiatry. Individual CAM treatments were reviewed with regard to efficacy in MDD, as well as risks and benefits. Literature searches included MEDLINE and PsycINFO reviews and manual reference searches; electronic searches were limited to English-language publications from 1965 to January 2010 (but manual searches were not restricted by language). Treatments were selected for this review on the basis of (1) published randomized controlled trials in MDD and (2) widespread use with important clinical safety or public health significance relevant to psychiatric practice. An action plan is presented based on needs pertaining to CAM and psychiatry. CONSENSUS PROCESS: Consensus was reached by group conferences. Written iterations were drafted and sent out among group members prior to discussion, resolution of any differences of interpretation of evidence, and final approval. CONCLUSIONS: A review of randomized controlled trials for commonly used CAM treatments such as omega-3 fatty acids, St John's wort (Hypericum), folate, S-adenosyl-L-methionine (SAMe), acupuncture, light therapy, exercise, and mindfulness psychotherapies revealed promising results. More rigorous and larger studies are recommended. Each CAM treatment must be evaluated separately in adequately powered controlled trials. At this time, several CAM treatments appear promising and deserve further study. The greatest risk of pursuing a CAM therapy is the possible delay of other well established treatments. Clinical, research, and educational initiatives designed to focus on CAM in psychiatry are clearly warranted due to the widespread use of CAM therapies. PMID- 20573327 TI - Complementary and alternative medicine for major depressive disorder: a meta analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. AB - OBJECTIVE: To compare patient characteristics, placebo-response rates, and outcome differences in active treatment compared to placebo in randomized controlled trials (RCTs) of complementary and alternative medicine (CAM) and standard antidepressants for major depressive disorder (MDD). DATA SOURCES: Eligible studies were first identified using searches of PubMed/MEDLINE, restricted to English, by cross-referencing the search term placebo with each of the antidepressants (those that had received letters of approval by the US, Canadian, or EU drug regulatory agencies for the treatment of MDD) and selected CAM agents. These searches were limited to articles published between January 1, 1980, and September 15, 2009 (inclusive). Reference lists from identified studies were also searched for studies eligible for inclusion. STUDY SELECTION: We selected RCTs for MDD that included validated diagnostic assessment and baseline/outcome measures of illness severity. Assessment was limited to widely used CAM agents most frequently studied in RCTs with pill placebo: St John's wort, omega-3 fatty acids, and S-adenosyl-L-methionine (SAMe). DATA SYNTHESIS: Of eligible publications, 173 reported results of 1 trial, and 5 included > 1 trial, representing a total of 185 RCTs. Patient variables, including illness severity, were similar across CAM and antidepressant RCTs, except for a higher proportion of women in CAM studies (P = .0003). Random-effects meta-analysis indicated that both antidepressant and CAM monotherapy resulted in superior response rates compared with placebo. Placebo-response rates were significantly lower for patients enrolled in CAM versus antidepressant RCTs (P = .002). Meta-regression analyses yielded no significant differences in the relative risk of prematurely discontinuing therapy due to any reason between active treatment and placebo for antidepressant and CAM RCTs, although discontinuation due to adverse events was higher in antidepressant RCTs compared to CAM RCTs (P = .007). CONCLUSIONS: Participants in CAM trials were more likely to be female and to have a lower placebo-response rate compared to those in standard antidepressant trials for MDD. Trials of standard antidepressants and CAM therapies were composed of patients with similar depression severity. PMID- 20573328 TI - Risk of cerebrovascular adverse events in older adults using antipsychotic agents: a propensity-matched retrospective cohort study. AB - OBJECTIVE: To compare the risk of cerebrovascular adverse events with second generation antipsychotic users versus those taking first-generation antipsychotics in community-dwelling older adults. METHOD: A population-based retrospective cohort study matched on propensity score was used to examine the risk of cerebrovascular adverse events in second-generation antipsychotic users compared to first-generation antipsychotic users. IMS LifeLink Health Plan Claims Database was used to identify older adults (> or = 50 years) taking second generation or first-generation antipsychotic agents from July 1, 2000, to December 31, 2007. Cox proportional hazards regression model stratified on matched pairs was used to examine the risk of hospitalization or emergency visits due to cerebrovascular adverse events within 1 year of follow-up (primary outcome measure). The covariates adjusted for include duration of therapy and exposure to other medication increasing risk of cerebrovascular adverse events. RESULTS: A total of 11,160 older adults (5,580 second-generation and 5,580 first-generation antipsychotic users) matched on propensity score was obtained. Regression analysis revealed that no statistically significant difference exists between second-generation and first-generation antipsychotic users with respect to risk of cerebrovascular adverse events (hazard ratio [HR], 0.858; 95% CI, 0.689 1.446). However, duration of therapy between 30-90 days (HR, 1.707; 95% CI, 1.174 2.481) and more than 90 days (HR, 1.570; 95% CI, 1.132-2.176) was associated with increased risk of cerebrovascular adverse events compared to duration of therapy less than 30 days. CONCLUSIONS: The use of second-generation antipsychotic agents was found not to be associated with increased risk of cerebrovascular adverse events compared to first-generation agents in older adults. However, long-term use of second- and first-generation antipsychotic agents is associated with increased risk of cerebrovascular adverse events. PMID- 20573329 TI - Strategies in treatment of suicidality: identification of common and treatment specific interventions in empirically supported treatment manuals. AB - OBJECTIVE: Many reports of treatments for suicidal patients claim effectiveness in reducing suicidal behavior but fail to demonstrate which treatment interventions, or combinations thereof, diminish suicidality. In this study, treatment manuals for empirically supported psychological treatments for suicidal patients were examined to identify which interventions they had in common and which interventions were treatment-specific. METHOD: Empirically supported treatments for suicidality were identified through a literature search of PsychLit and MEDLINE for the years 1970-2007, employing the following search strategy: [suicide OR parasuicide] AND [therapy OR psychotherapy OR treatment] AND [random OR randomized]. After identifying the reports on randomized controlled studies that tested effectiveness of different treatments, the reference list of each report was searched for further studies. Only reports published in English were included. To ensure that rated manuals actually correspond to the delivered and tested treatments, we included only treatment interventions with explicit adherence rating and scoring and with adequate adherence ratings in the published studies. Five manualized treatments demonstrating efficacy in reducing suicide risk were identified and were independently evaluated by raters using a list of treatment interventions. RESULTS: The common interventions included a clear treatment framework; a defined strategy for managing suicide crises; close attention to affect; an active, participatory therapist style; and use of exploratory and change-oriented interventions. Some treatments encouraged a multimodal approach and identification of suicidality as an explicit target behavior, and some concentrated on the patient-therapist relationship. Emphasis on interpretation and supportive interventions varied. Not all methods encouraged systematic support for therapists. CONCLUSION: This study identified candidate interventions for possible effectiveness in reducing suicidality. These interventions seem to address central characteristics of suicidal patients. Further studies are needed to confirm which interventions and which combinations thereof are most effective. PMID- 20573330 TI - The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission. AB - OBJECTIVE: To describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis. METHOD: A naturalistic, prospective follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients, followed between January 1998 and April 2005, at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. EPPIC is a frontline public mental health early psychosis program, servicing a geographically defined catchment area with a population of about 800,000 people. The main outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, the Quality of Life Scale, and the remission criteria developed by the Remission in Schizophrenia Working Group. RESULTS: Follow-up information was collected on up to 90.0% (n = 651) of the baseline cohort of 723 participants, with 66.9% (n = 484) interviewed. In the last 2 years, 57% of individuals with schizophrenia/schizophreniform, 54% with schizoaffective disorder, 62% with affective psychosis, and 68% with other psychotic disorders reported some paid employment. Depending upon the criteria applied, symptomatic remission at follow-up was observed in 37%-59% of the cohort. Social/vocational recovery was observed in 31% of the cohort. Approximately a quarter achieved both symptomatic remission and social/vocational recovery. CONCLUSION: The relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs; however it is premature to draw firm conclusions. There was no control group and there are many differences between the relevant comparison studies and the present one. Although difficult to conduct, large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs. PMID- 20573331 TI - Donepezil and concurrent sertraline treatment is associated with increased hippocampal volume in a patient with depression. PMID- 20573332 TI - One-year outcome after preconception consultation in women with bipolar disorder. PMID- 20573333 TI - Psychiatric discharge against medical advice is a risk factor for suicide but not for other causes of death. PMID- 20573334 TI - Outcome of oncoplastic breast surgery in 90 prospective patients. AB - BACKGROUND: Oncoplastic breast surgery refers to a wide range of techniques with a parallel goal of safely removing all malignant breast tissue while achieving the best possible esthetic outcome. We report the results of our oncoplastic breast operations from 2005 to 2007. METHODS: Ninety selected breast cancer patients were treated with a variety of oncoplastic operations. The patients were prospectively monitored. Radiotherapy and systemic adjuvant treatment were given according to national guidelines. RESULTS: Fifteen patients had an immediate surgical complication, of which 8 required a reoperation. Eleven patients had an inadequate surgical margin and required a completion mastectomy. During a median follow-up of 26 months no local or regional recurrences were noticed. Three patients developed distant metastases. CONCLUSIONS: Oncoplastic breast surgery offers tools for breast conservation in patients otherwise destined for mastectomy or poor esthetic outcome. Despite the high proportion of patients in this series with large-volume ductal carcinoma in situ (DCIS) or extensive intraductal component, the use of oncoplastic techniques achieved negative margins with acceptable cosmetic results in the majority (84%) of patients. PMID- 20573335 TI - Compliance with guidelines to prevent surgical site infections: As simple as 1-2 3? AB - BACKGROUND: the purpose of this study was to assess predictive factors and compliance with surgical site infection (SSI) prevention guidelines at 2 county hospitals. DESIGN: chart review and analysis of laparotomy patients undergoing colorectal, hysterectomy, or abdominal vascular procedures over two 6-month periods 1 year apart and evaluation of safety climate using the Safety Attitudes Questionnaire (SAQ). RESULTS: overall compliance with all antibiotic prophylaxis guidelines was 62% (n = 442). Gynecologic surgery was an independent predictor of compliance with antibiotic prophylaxis guidelines in elective cases, and nonemergency status was an independent predictor when all cases were considered. Postoperative normothermia was predicted by hospital, procedure length, initial intraoperative temperature, and service. The SAQ had a 91% response rate. Contrary to expected, safety domain scores and agreement with statements on collaboration and teamwork were not predictive of compliance. CONCLUSION: interventions to improve poor compliance with infection prevention guidelines must be multifaceted, hospital- and service-specific, and resilient during emergencies. Good safety and teamwork climate are not sufficient. PMID- 20573336 TI - Operative performance in laparoscopic cholecystectomy using the Procedural-Based Assessment tool. AB - AIMS: The Intercollegiate Surgical Curriculum Project (ISCP) has devised assessment tools for index operations to assess trainee technical skills. In this study we used the Procedural-Based Assessment (PBA) tool to evaluate operations performed by trainees. METHODS: Live and simulated laparoscopic cholecystectomies were performed by trainees. Two experienced surgeons assessed each operation blindly and independently. RESULTS: Eighty-four live (supervised) and 112 simulated (unsupervised) operations were performed by 28 trainees. Mean inter rater reliability was kappa = .86 and .84 for live and simulated operations, respectively. Construct validity using Mann-Whitney for generic technical skills was significant for live and simulated operations, P < or = .05. Assessing specific technical skills showed construct validity for simulated unsupervised operations only, Mann-Whitney P < .05, but not for supervised live operations, Mann-Whitney P > .05. CONCLUSIONS: The PBA showed good inter-rater reliability. Assessing generic technical skills, PBA showed construct validity for both types of operations and for specific technical skills in the unsupervised simulated operations. We conclude that the PBA seems to be a reliable and valid assessment tool for generic technical skills in unsupervised simulated and live supervised laparoscopic cholecystectomies. PMID- 20573337 TI - Priming associations between bodily sensations and catastrophic misinterpretations: Specific for panic disorder? AB - Cognitive models assume that panic disorder is characterised by a tendency to misinterpret benign bodily symptoms (e.g. breathlessness) in a catastrophic fashion (e.g. suffocation). This is a central part of the cognitive model which presents a core focus for treatment. Several studies have supported this hypothesis. These studies have, however, almost always relied on self-report. In addition to susceptibility to biases (e.g. distortions of memory), a limitation of research based on verbal report is its inability to capture the spontaneous/automatic nature that is attributed to these catastrophic interpretations. The present paper reports on two experiments in which a priming procedure was used to test the hypothesis that panic disorder is characterised by spontaneous catastrophic interpretations and whether this effect is 'specific' to panic disorder. In line with predictions from the cognitive model, it was observed in the first experiment that the panic group demonstrated facilitated responses to trials consisting of a 'symptom' prime and a 'catastrophic outcome' target (e.g. breathlessness - suffocate). Similar effects were not observed for an anxious control group and a nonclinical control group, supporting the specificity of this effect. Interestingly, however, significant priming effects were observed for a group of mental health professionals (part of the healthy control group) who had no history of panic disorder. Subsequently, this unexpected observation was explicitly addressed in a second experiment, which confirmed the findings of Experiment 1. Together, these results suggest that associations between mental representations of benign bodily symptoms and catastrophic outcomes might develop as part of professional knowledge and experience, and should not necessarily be viewed as pathogenic. Theoretical and clinical implications are discussed. PMID- 20573338 TI - Comorbidity in youth with specific phobias: Impact of comorbidity on treatment outcome and the impact of treatment on comorbid disorders. AB - The purpose of the present study was twofold. In an analysis of data from an existing randomized control trial of brief cognitive behavioral treatment on specific phobias (One-Session Treatment, OST; Ollendick et al., 2009), we examined 1) the effect of comorbid specific phobias and other anxiety disorders on treatment outcomes, and 2) the effect of treatment of the specific phobia on these co-occurring disorders. These relations were explored in 100 youth presenting with animal, natural environment, situational, and "other" types of phobia. Youth were reliably diagnosed with the Anxiety Disorders Interview Schedule for DSM-IV: Child and Parent versions (Silverman & Albano, 1996). Clinician severity ratings at post-treatment and 6-month follow-up were examined as were parent and child treatment outcome satisfaction measures. Results indicated that the presence of comorbid phobias or anxiety disorders did not affect treatment outcomes; moreover, treatment of the targeted specific phobias led to significant reductions in the clinical severity of other co-occurring specific phobias and related anxiety disorders. These findings speak to the generalization of the effects of this time-limited treatment approach. Implications for treatment of principal and comorbid disorders are discussed, and possible mechanisms for these effects are commented upon. PMID- 20573340 TI - [Phlebology training of general and digestive tract surgery residents (MIR)]. PMID- 20573339 TI - Exaggerated and disconnected insular-amygdalar blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. AB - BACKGROUND: Intimate-partner violence (IPV) is one of the most common causes of posttraumatic stress disorder (PTSD) among women. PTSD neuroimaging studies have identified functional differences in the amygdala and anterior cingulate cortex (ACC)/medial prefrontal cortex during emotion processing. Recent investigations of the limbic sensory system and its associated neural substrate, the insular cortex, have demonstrated its importance for emotional awareness. This study examined the hypothesis that women with IPV-PTSD show a dysregulation of this limbic sensory system while processing threat-related emotional faces. METHODS: 12 women with IPV-PTSD and 12 nontraumatized comparison women underwent blood oxygenation level-dependent functional magnetic resonance imaging while completing an emotional face-matching task. RESULTS: IPV-PTSD subjects relative to comparison subjects displayed increased activation of the anterior insula and amygdala and decreased connectivity among the anterior insula, amygdala, and ACC while matching to fearful versus happy target faces. A similar pattern of activation differences was also observed for angry versus happy target faces. IPV PTSD subjects relative to comparison subjects also displayed increased dorsal ACC/medial prefrontal cortex activation and decreased ventral ACC activation when matching to a male versus a female target, and the extent of increased dorsal ACC activation correlated positively with hyperarousal symptoms. CONCLUSIONS: Women with IPV-PTSD display hyperactivity and disconnection among affective and limbic sensory systems while processing threat-related emotion. Furthermore, hyperactivity of cognitive-appraisal networks in IPV-PTSD may promote hypervigilant states of awareness through an exaggerated sensitivity to contextual cues, i.e., male gender, which relate to past trauma. PMID- 20573341 TI - Implicit learning as an ability. AB - The ability to automatically and implicitly detect complex and noisy regularities in the environment is a fundamental aspect of human cognition. Despite considerable interest in implicit processes, few researchers have conceptualized implicit learning as an ability with meaningful individual differences. Instead, various researchers (e.g., Reber, 1993; Stanovich, 2009) have suggested that individual differences in implicit learning are minimal relative to individual differences in explicit learning. In the current study of English 16-17year old students, we investigated the association of individual differences in implicit learning with a variety of cognitive and personality variables. Consistent with prior research and theorizing, implicit learning, as measured by a probabilistic sequence learning task, was more weakly related to psychometric intelligence than was explicit associative learning, and was unrelated to working memory. Structural equation modeling revealed that implicit learning was independently related to two components of psychometric intelligence: verbal analogical reasoning and processing speed. Implicit learning was also independently related to academic performance on two foreign language exams (French, German). Further, implicit learning was significantly associated with aspects of self-reported personality, including intuition, Openness to Experience, and impulsivity. We discuss the implications of implicit learning as an ability for dual-process theories of cognition, intelligence, personality, skill learning, complex cognition, and language acquisition. PMID- 20573342 TI - Word segmentation with universal prosodic cues. AB - When listening to speech from one's native language, words seem to be well separated from one another, like beads on a string. When listening to a foreign language, in contrast, words seem almost impossible to extract, as if there was only one bead on the same string. This contrast reveals that there are language specific cues to segmentation. The puzzle, however, is that infants must be endowed with a language-independent mechanism for segmentation, as they ultimately solve the segmentation problem for any native language. Here, we approach the acquisition problem by asking whether there are language-independent cues to segmentation that might be available to even adult learners who have already acquired a native language. We show that adult learners recognize words in connected speech when only prosodic cues to word-boundaries are given from languages unfamiliar to the participants. In both artificial and natural speech, adult English speakers, with no prior exposure to the test languages, readily recognized words in natural languages with critically different prosodic patterns, including French, Turkish and Hungarian. We suggest that, even though languages differ in their sound structures, they carry universal prosodic characteristics. Further, these language-invariant prosodic cues provide a universally accessible mechanism for finding words in connected speech. These cues may enable infants to start acquiring words in any language even before they are fine-tuned to the sound structure of their native language. PMID- 20573343 TI - Determination of foveal avascular zone in diabetic retinopathy digital fundus images. AB - Monitoring FAZ area enlargement enables physicians to monitor progression of the DR. At present, it is difficult to discern the FAZ area and to measure its enlargement in an objective manner using digital fundus images. A semi-automated approach for determination of FAZ using color images has been developed. Here, a binary map of retinal blood vessels is computer generated from the digital fundus image to determine vessel ends and pathologies surrounding FAZ for area analysis. The proposed method is found to achieve accuracies from 66.67% to 98.69% compared to accuracies of 18.13-95.07% obtained by manual segmentation of FAZ regions from digital fundus images. PMID- 20573344 TI - Organotin intake through fish consumption in Finland. AB - BACKGROUND: Organotin compounds (OTCs) are a large class of synthetic chemicals with widely varying properties. Due to their potential adverse health effects, their use has been restricted in many countries. Humans are exposed to OTCs mostly through fish consumption. OBJECTIVES: The aim of this study was to describe OTC exposure through fish consumption and to assess the associated potential health risks in a Finnish population. METHODS: An extensive sampling of Finnish domestic fish was carried out in the Baltic Sea and freshwater areas in 2005-2007. In addition, samples of imported seafood were collected in 2008. The chemical analysis was performed in an accredited testing laboratory during 2005 2008. Average daily intake of the sum of dibutyltin (DBT), tributyltin (TBT), triphenyltin (TPhT) and dioctyltin (DOT) (SigmaOTCs) for the Finnish population was calculated on the basis of the measured concentrations and fish consumption rates. RESULTS: The average daily intake of SigmaOTCs through fish consumption was 3.2ng/kgbwday(-1), which is 1.3% from the Tolerable Daily Intake (TDI) of 250ng/kgbwday(-1) set by the European Food Safety Authority. In total, domestic wild fish accounted for 61% of the SigmaOTC intake, while the intake through domestic farmed fish was 4.0% and the intake through imported fish was 35%. The most important species were domestic perch and imported salmon and rainbow trout. CONCLUSIONS: The Finnish consumers are not likely to exceed the threshold level for adverse health effects due to OTC intake through fish consumption. PMID- 20573345 TI - Endoscopic transesophageal mediastinal lymph node dissection and en bloc resection by using mediastinal and thoracic approaches (with video). AB - BACKGROUND: The criterion standard for sampling mediastinal lymph nodes is cervical mediastinoscopy. Current methods that require transthoracic or cervical incisions can result in significant postoperative pain. OBJECTIVE: To determine the feasibility of a novel, transesophageal endoscopic technique for mediastinal lymph node dissection and en bloc resection. DESIGN: Nonsurvival and survival animal study. SETTING: Animal trial at a tertiary-care academic center. SUBJECTS: This study involved 12 Yorkshire swine. INTERVENTION: An endoscopic cap band mucosectomy device was used to create an esophageal mucosal defect. By using the tip of the endoscope and biopsy forceps, a submucosal tunnel was fashioned, and, within the submucosal space, a hook-knife incised the muscular esophageal wall. The endoscope was then advanced into the mediastinum and chest. Mediastinoscopy and thoracoscopy were performed to identify lymph node stations. Prototype endoscopic devices permitted lymph node dissection prior to removal with an electrocautery snare. A covered prototype stent was placed over the mucosectomy site. MAIN OUTCOME MEASUREMENTS: Feasibility of endoscopic transesophageal lymphadenectomy. RESULTS: Three lymph nodes (1 para-aortic and 2 right paratracheal) were removed in the 3 nonsurvival swine. Nine swine were survived for 14 days (range 13-14 days) and had a total of 7 lymph nodes (2 para-aortic and 5 paratracheal) removed. Two swine had no endoscopically visible lymph nodes in the mediastinum or chest. Lymph node dissection and resection was successful in all cases where lymph nodes were identified. Lymphadenectomy was completed in a median time of 20.0 minutes (range 8-60 minutes); median total procedure time was 70.0 minutes (range 28-105 minutes). Median lymph node size was 1.1 cm (range 0.6-1.4 cm). LIMITATIONS: Animal study. CONCLUSION: An endoscopic transesophageal approach can accomplish mediastinal lymph node dissection and en bloc resection and provides architecturally intact lymph node specimens for histologic examination. PMID- 20573346 TI - Determination of optimal monopolar coagulation settings for upper GI bleeding in a pig model. AB - BACKGROUND: Monopolar electrocautery has had a limited role in the endoscopic therapy of nonvariceal upper GI bleeding because of the lack of specifically designed endoscopic instruments and limited data on how to use this technology for endoscopic applications. OBJECTIVE: To determine the optimal power settings and durations of endoscopic monopolar electrocautery for nonvariceal gastric bleeding. DESIGN: Twelve pigs underwent creation of cautery lesions by using a novel monopolar electrocautery device designed for endoscopic hemostasis control. The efficacy as measured by the depth of cautery and safety of monopolar electrocoagulation were evaluated in acute and survival phases. INTERVENTIONS: Monopolar electrocautery was applied to the stomach with power settings of 25, 50, and 75 W for durations of 2 to 5 seconds. MAIN OUTCOME MEASUREMENT: The extent of cautery injury was assessed histologically by a blinded pathologist. RESULTS: An optimal cautery effect was achieved with 50 W of power and durations of cautery of 2 and 3 seconds. For 25 W, durations of cautery of 4 and 5 seconds resulted in good but often superficial cautery effect. For 75 W, durations of cautery of 2 and 3 seconds resulted in good cautery effect, but with marginal safety. The visual diameter of monopolar cautery lesions correlated with the histological depth of the cautery lesions. No adverse effects were observed. LIMITATIONS: Study conducted in a nonbleeding pig stomach model; thus, results may not apply to control of GI bleeding in patients. CONCLUSIONS: Based on a nonbleeding pig model, we suggest that the initial settings for monopolar soft coagulation in clinical use should be 50 W for 2 to 3 seconds. PMID- 20573347 TI - Averting maternal death and disability. Editor's comment. PMID- 20573348 TI - Long-term vaginal administration of Lactobacillus rhamnosus as a complementary approach to management of bacterial vaginosis. AB - OBJECTIVE: To investigate the advantages of long-term vaginal administration of Lactobacillus rhamnosus after oral treatment with metronidazole to prevent the recurrence of bacterial vaginosis (BV). METHODS: A total of 49 women with a diagnosis of BV were randomized into 2 groups. Group A was treated with a twice daily dose of 500 mg oral metronidazole for 7 days. Group B was treated with the same schedule followed by a once-weekly vaginal application of 40 mg of Lactobacillus rhamnosus for 6 months. A non-parametric analysis of variance for repeated measures was used to test whether there were significant changes in the vaginal ecosystems in the 2 groups. RESULTS: During the first 6 months of follow up, a constant percentage (96%) of patients in group B had a balanced vaginal ecosystem. Follow-up over 12 months showed no statistically significant difference among vaginal ecosystems in patients in group B (P=0.40), whereas in group A there was a significant increase in the number of women with abnormal flora over time (P=0.01). CONCLUSION: The vaginal administration of the probiotic Lactobacillus rhamnosus allows stabilization of the vaginal ecosystem and reduces the recurrence of BV. PMID- 20573349 TI - Concurrent musculoskeletal dynamics and finite element analysis predicts altered gait patterns to reduce foot tissue loading. AB - Current computational methods for simulating locomotion have primarily used muscle-driven multibody dynamics, in which neuromuscular control is optimized. Such simulations generally represent joints and soft tissue as simple kinematic or elastic elements for computational efficiency. These assumptions limit application in studies such as ligament injury or osteoarthritis, where local tissue loading must be predicted. Conversely, tissue can be simulated using the finite element method with assumed or measured boundary conditions, but this does not represent the effects of whole body dynamics and neuromuscular control. Coupling the two domains would overcome these limitations and allow prediction of movement strategies guided by tissue stresses. Here we demonstrate this concept in a gait simulation where a musculoskeletal model is coupled to a finite element representation of the foot. Predictive simulations incorporated peak plantar tissue deformation into the objective of the movement optimization, as well as terms to track normative gait data and minimize fatigue. Two optimizations were performed, first without the strain minimization term and second with the term. Convergence to realistic gait patterns was achieved with the second optimization realizing a 44% reduction in peak tissue strain energy density. The study demonstrated that it is possible to alter computationally predicted neuromuscular control to minimize tissue strain while including desired kinematic and muscular behavior. Future work should include experimental validation before application of the methodology to patient care. PMID- 20573350 TI - Mobile phase selection for the combined use of liquid chromatography-inductively coupled plasma mass spectrometry and electrospray ionisation mass spectrometry. AB - Four different organic solvents: dimethylformamide, 1,4-dioxane, n-propanol and ethanol were evaluated as alternative organic modifiers to acetonitrile for liquid chromatography (LC) separations. The aim was to establish common sets of chromatographic conditions that could be applied for LC hyphenation to inductively coupled plasma mass spectrometry (ICPMS) as well as to electrospray ionization MS (ESIMS). The approach was to evaluate candidate solvents that, compared to acetonitrile, potentially could give improved analytical performance (low solvent vapor loading, maximized analyte sensitivity and minimized carbon depositions on instrumental parts) in ICPMS analysis while retaining chromatographic and ESIMS performances. The study showed that dimethylformamide, 1,4-dioxane, n-propanol and ethanol all can be advantageous chromatographic modifiers for LC-ICPMS analysis, giving superior performance compared to acetonitrile. For the combined use of LC-ICPMS and LC-ESIMS with a common set of chromatographic conditions, n-propanol gave the best overall performance. The 195Pt+ signal in ICPMS was continuously monitored during a 0-60% organic solvent gradient and at 25% of organic modifier, 100% of the signal obtained at the gradient start was preserved for n-propanol compared to only 35% of the signal when using acetonitrile. Platinum detection limits were 5-8 times lower using n propanol compared with acetonitrile. Signal-to-noise ratio in continuous ESIMS signal measurements was 100, 90 and 110 for a 100 microg/ml solution of leucine enkephaline using acetonitrile, ethanol and n-propanol, respectively. Chromatographic efficiency in reversed phase separations was preserved for n propanol compared to acetonitrile for the analysis of the whole protein cytochrome C and the peptide bacitracin on a column with particle and pore sizes of 5 microm and 300 A, but slightly deteriorated for the separation of the peptides leucine-enkephaline and bacitracin on a 3 microm and 90 A column as the peak width at half height for both peptides increased by a factor of two. The performance on the smaller dimensioned column could however be improved by running the separations at 40 degrees C. PMID- 20573351 TI - The stability of high internal phase emulsions at low surfactant concentration studied by small angle neutron scattering. AB - The changes in structure of high internal phase emulsions at low concentrations and at elevated temperature are reported for comparison with the same emulsions under conditions well away from instability. Small angle neutron scattering measurements on aqueous ammonium nitrate droplets dispersed in hexadecane and stabilized by very small quantities of a polyisobutylene-based surfactant (PIBSA) as well as related inverse micellar solutions in hexadecane, have been made as a function of temperature and surfactant concentration. Experimental conditions here favour larger and more deformable droplets than in previous studies. Besides the expected micelles and adsorbed surfactant, planar bilayers of micron lateral extent between touching droplets cover 20% of the droplet surface. Another difference from previous experiments is that the oil phase in the emulsions, and corresponding inverse micellar solutions are different in micellar radii and composition. The differences, and changes with surfactant concentration and temperature, are attributed to fractionation of the polydisperse PIBSA in the emulsions, but not the inverse micellar solutions. At low PIBSA concentration and high temperature the SANS shows emulsion decomposing into separate oil and aqueous phases. This occurs when the micelle concentration reaches a very small but measurable value. The inverse micelles may suppress by steric action long wavelength unstable capillary waves in the bilayers. Depletion repulsion forces here have a minor role in the emulsion stabilization. PMID- 20573352 TI - An unexpected solvent effect on the self-assembly of a 1,7-bis-pyridinoyl perylene diimide amphiphile. AB - In this paper, we report that a 1,7-bis-pyridinoyl perylene diimide amphiphile undergoes distinctly different self-assembly in methanol compared to ethanol. This amphiphile forms hollow nanospheres in methanol, whereas in ethanol, it self assembles into microrose flowers which consist of several soft nanoplates packing like rose petals. Studies of the concentration-dependent absorption spectra confirmed this solvent effect. The most distinct spectral features were the A(0 0)/A(0-1) and A(0-0)/A(S)(0-)(S)(2) values. These spectral changes were explained in terms of the Franck-Condon factors. PMID- 20573353 TI - Polymer/silica composite of core-shell type by polymer swelling in TEOS. AB - Monodisperse polymer/silica composite material with a polymer as the core and hydrophilic silica gel as the shell was prepared by a two-stage procedure. In the first stage, the swelling of Amberlite XAD7HP particles in tetraethoxysilane (TEOS) was performed. Subsequently a portion of the XAD7HP particles impregnated with TEOS were transferred to acidic aqueous solution to facilitate a sol-gel process of the silica precursor. This procedure is assessed as a potential route to a composite material with a core-shell morphology. Scanning electron microscopy and (29)Si MAS NMR indicated the formation of silica microfibers on polymer beads. The silica microfibers were anchored in the polymer matrix. In consequence, the silica shell exhibited relatively high mechanical stability. The swelling of the polymer and the formation of the silica phase substantially changed the porosity of the initial polymer material. The final composite surprisingly exhibited very homogeneous porosity. The textural characteristics of the investigated materials were defined by nitrogen adsorption-desorption at 77K. PMID- 20573354 TI - Phase behavior of liquid-crystalline emulsion systems. AB - The phase behavior of a mixture containing a surfactant, fatty alcohols and water has been analyzed. Depending on the amount of surfactant, i.e. N-(3 dimethylaminopropyl) octadecanamide, the emulsion-like system forms different microstructures. With increasing surfactant content the formulation evolves from a system with lyotropic lamellar phases to a system with crystal layer phases. (13)C-CPMAS NMR studies carried out at varying surfactant levels showed significant differences in the behavior of the system. Using (2)H and (13)C-CPMAS NMR, X-ray scattering, DSC and polarization microscopy a phase diagram of this system could be derived. Additionally, ultrasonic velocity measurements showed that the ripening process of the emulsions can take up to 2 weeks and longer. PMID- 20573355 TI - Time-resolved quasi-elastic laser scattering study demonstrating heterogeneity of interfacial tension at the water/nitrobenzene interface after introduction of sodium alkylsulfate. AB - The interface of a biphasic system of water and nitrobenzene exhibits a rapid flip motion and a tangential flow, so-called Marangoni convection, accompanying a pulse-like change of interfacial electrical potential when an aqueous solution of sodium alkylsulfate is introduced to the interface through a capillary. Although it is conventionally known that the Marangoni convection is triggered by heterogeneity of the interfacial tension, the heterogeneity of the interfacial tension of this system has not been directly measured. Here, we employed a time resolved quasi-elastic laser scattering method with a time resolution of 200 ms to trace the time course of the interfacial tension at the water/nitrobenzene interface, and we demonstrated the first experimental evidence for the heterogeneity of the interfacial tension. Moreover, we found that the homogeneity of interfacial tension was restored within 1 s and that, in the presence of an electrolyte in the water phase, the surfactant molecules were homogeneously adsorbed on the interface immediately after they were conveyed by the tangential flow at the interface, whereas in the absence of electrolyte, the surfactant molecules were distributed only in the bulk phases. PMID- 20573356 TI - Interfacial displacement of nanoparticles by surfactant molecules in emulsions. AB - The remarkable stability of nanoparticles attached to oil-water interfaces in macroemulsions hinders controlled detachment of these particles from emulsions. In this work it is shown that adding surfactant molecules which preferentially adsorb at the oil-water interface displaces nanoparticles from the interface. Surfactant adsorption at the oil-water interface is energetically favoured and readily occurs on mixing nanoparticle-stabilised oil-in-water emulsions with surfactant solutions. Depending on the surfactant concentration, there is a significant reduction in the interfacial tension. Hence there is substantial fragmentation of the oil droplets and foaming of the emulsion during mixing. Surfactant concentrations above the critical micelle concentration are required to achieve complete interfacial displacement and hence recovery of the nanoparticles from the emulsions. The effects of surfactant addition have important implications for tailoring the interfacial composition of emulsions. PMID- 20573357 TI - Lensless microscopy technique for static and dynamic colloidal systems. AB - We present the application of a lensless microscopy technique known as digital in line holographic microscopy (DIHM) to image dynamic and static colloidal systems of microspheres. DIHM has been perfected up to the point that submicrometer lateral resolution with several hundreds of micrometers depth of field is achieved with visible light; it is shown that the lateral resolution of DIHM is enough to resolve self-assembled colloidal monolayers built up from polystyrene spheres with submicrometer diameters. The time resolution of DIHM is of the order of 4 frames/s at 2048 x 2048 pixels, which represents an overall improvement of 16 times the time resolution of confocal scanning microscopy. This feature is applied to the visualization of the migration of dewetting fronts in dynamic colloidal systems and the formation of front-like arrangements of particles. PMID- 20573358 TI - [Life-threatening ketamine overdose]. PMID- 20573359 TI - [Systemic amyloidosis AA in a liver transplant recipient with biliary complications in the posttransplant period]. PMID- 20573360 TI - [From evidence to recommendation: a pending job]. PMID- 20573361 TI - [Functional status and in-hospital mortality]. PMID- 20573362 TI - [Cardiac abnormalities in osteogenesis imperfecta. Case-control echocardiographic study]. AB - BACKGROUND AND OBJECTIVES: Osteogenesis imperfecta is a rare disease with abnormal synthesis of type 1 collagen that affects diverse extra-skeletal tissues. Aortic root dilatation and valvular dysfunction have been described. Our purpose was to evaluate the prevalence of cardiac abnormalities in patients with osteogenesis imperfecta in comparison with an age and sex-matched control group of healthy people. PATIENTS AND METHODS: We prospectively studied 26 patients with osteogenesis imperfecta and compared them with 25 healthy people. All patients underwent a transthoracic standard M-mode, 2D and colour Doppler study. RESULTS: We did not find significant differences between both groups in the left ventricular diastolic and systolic function and the incidence of valvulopathies. The dimensions of the aortic root, left atrium and left ventricle when indexed by body surface area were significantly larger in patients with osteogenesis imperfecta compared with the control group, which was probably due to the reduced body surface of these patients. However there was a significant difference in the aortic root/telediastolic diameter of left ventricle ratio independent of the body surface, which was higher in patients with osteogenesis imperfecta. CONCLUSIONS: The incidence of valvular disease in osteogenesis imperfecta is similar to that of the normal population. However aortic root is larger in the former patients and is related to the left ventricular diastolic diameter. PMID- 20573363 TI - Crocins transport in Crocus sativus: the long road from a senescent stigma to a newborn corm. AB - Saffron, the desiccated stigmas of Crocus sativus, is highly appreciated by its peculiar colour, flavour and aroma. The main compounds that accumulated throughout stigma development in C. sativus are crocetin, its glucoside derivatives, crocins, and picrocrocin, all of which increased as stigmas reached a fully developed stage. After anthesis, and in the absence of fertilization, the flower enters in a senescence programme, which represents the ultimate stage of floral development and results in wilting of whole flower. The programmed senescence of flowers allows the removal of a metabolically active tissue. We studied the composition of saffron apocarotenoids during the senescence of C. sativus flowers, and observed that changes in crocins were due to their transport from the senescent stigma to the ovaries and the developing corm. Afterwards, deglucosylation of crocins in these tissues results in crocetin accumulation. This mobilization mimics the export to storage cells (resorbed) of different compounds during leaf senescence avoiding loss of nutrients in leaves that would otherwise be cycled back into the soil system through leaf litter decomposition. In C. sativus, the resorbed apocarotenoids are stored within the developing corm, where they are not further detected in the advanced stages of development, suggesting that they are metabolized during the early and active phases of corm development, where the glucose molecules from crocins might contribute to cell initiation and elongation. PMID- 20573364 TI - Structural characterization of a pectic polysaccharide from Nerium indicum flowers. AB - A polysaccharide fraction, J6, was isolated from the hot-water extract of flowers of oleander Nerium indicum Mill., using ethanol precipitation, cetyltrimethylammonium bromide (CTAB) complexing, anion-exchange chromatography and gel permeation chromatography. J6 was found to contain L-rhamnose, L arabinose, D-galactose, and D-galacturonic acid, in the ratio of 10.1:49.8:30.1:10.0. Its structure was investigated by methylation analysis, periodate oxidation, Smith degradation, partial acid hydrolysis, electrospray ionization mass spectrometry and NMR spectroscopic methods. It was found that J6 is an RG-I type polysaccharide, which contains a rhamnogalacturonan backbone, with various branches attached to O-4 of L-rhamnose. The branches probably involve (1-->4)-beta-D-galactan, branched L-arabino-(1-->3)(1-->6)-beta-D galactan, and (1-->5)-alpha-L-arabinan. J6 stimulated NO production of macrophage RAW264.7 cells in a preliminary test. PMID- 20573365 TI - The role of lysine residue at amino acid position 165 of human immunodeficiency virus type 1 CRF01_AE Gag in reducing viral drug susceptibility to protease inhibitors. AB - Recombinant human immunodeficiency virus type 1 (HIV-1) containing a CRF01_AE Gag, AE-Gag62, was significantly less susceptible to protease inhibitors (PIs) than the subtype B reference strain, NL4-3; therefore, the mechanism of how AE Gag62 reduced viral drug susceptibility to PIs was studied in this report. The results showed that the lysine residue at amino acid position 165 (K165) of AE Gag62 played a role in reducing the drug susceptibility of the recombinant virus to PIs. In addition, K165 potentially appears more frequently in CRF01_AE viruses than in the viruses of other major HIV-1 subtypes. Although K165 had no effect on the extent of recombinant protease-mediated in vitro Gag cleavage, it enhanced the incorporation of the Gag-Pol precursor protein, p160, into virions. Taken together, these results suggest that K165 of CRF01_AE Gag affects the regulation of virion assembly or maturation, and reduces viral drug susceptibility to PIs. PMID- 20573366 TI - Subsurface iron and arsenic removal for shallow tube well drinking water supply in rural Bangladesh. AB - Subsurface iron and arsenic removal has the potential to be a cost-effective technology to provide safe drinking water in rural decentralized applications, using existing shallow tube wells. A community-scale test facility in Bangladesh was constructed for injection of aerated water (~1 m(3)) into an anoxic aquifer with elevated iron (0.27 mmolL(-1)) and arsenic (0.27MUmolL(-1)) concentrations. The injection (oxidation) and abstraction (adsorption) cycles were monitored at the test facility and simultaneously simulated in the laboratory with anoxic column experiments. Dimensionless retardation factors (R) were determined to represent the delayed arrival of iron or arsenic in the well compared to the original groundwater. At the test facility the iron removal efficacies increased after every injection-abstraction cycle, with retardation factors (R(Fe)) up to 17. These high removal efficacies could not be explained by the theory of adsorptive-catalytic oxidation, and therefore other ((a)biotic or transport) processes have contributed to the system's efficacy. This finding was confirmed in the anoxic column experiments, since the mechanism of adsorptive-catalytic oxidation dominated in the columns and iron removal efficacies did not increase with every cycle (stable at R(Fe)=~8). R(As) did not increase after multiple cycles, it remained stable around 2, illustrating that the process which is responsible for the effective iron removal did not promote the co-removal of arsenic. The columns showed that subsurface arsenic removal was an adsorptive process and only the freshly oxidized adsorbed iron was available for the co adsorption of arsenic. This indicates that arsenic adsorption during subsurface treatment is controlled by the amount of adsorbed iron that is oxidized, and not by the amount of removed iron. For operational purposes this is an important finding, since apparently the oxygen concentration of the injection water does not control the subsurface arsenic removal, but rather the injection volume. Additionally, no relation has been observed in this study between the amount of removed arsenic at different molar Fe:As ratios (28, 63, and 103) of the groundwater. It is proposed that the removal of arsenic was limited by the presence of other anions, such as phosphate, competing for the same adsorption sites. PMID- 20573367 TI - Comment on Schriks, M., Heringa, M.B., van der Kooi, M.M.E., de Voogt, P., van Wezel, A.P., 2010. Toxicological relevance of emerging contaminants for drinking water quality. Water Research 44, 461-476. PMID- 20573368 TI - World Health Organization classification of thymomas provides significant prognostic information for selected stage III patients: evidence from an international thymoma study group. AB - Information regarding prognosis of thymoma patients stratified by both World Health Organization classification and Masaoka staging system is very limited. Analyze 5-year survival data from a large number of thymoma patients stratified by both World Health Organization histologic type and Masaoka stage using meta analysis. Perform power analysis to estimate the number of cases that would be needed to test the null hypothesis to a power of 80%. Five-year survival data from 905 thymoma patients treated with thymectomy at seven hospitals in America, Japan, Korea, India, Italy, and Germany. Survival data was reported as "dead" or "alive" to facilitate meta-analysis. Significant differences were detected only when comparing survival rates of thymoma patients in stages I to III with those of stage IV disease. Analysis by World Health Organization histologic type and stage yielded significant differences only in patients with thymomas A vs. B2 and A vs. B3 in stage III disease. No significant data heterogeneity was detected with funnel plots and Egger's regression test. Power analysis estimated that a study with 7077 patients is needed to evaluate the prognostic significance of all thymomas stratified by both World Health Organization histologic type and stage to a power of 80%. Selected World Health Organization histologic types are significantly associated with prognosis in stage III thymoma patients and may help select individuals benefiting from neoadjuvant therapy. Power analysis shows that studies with much larger number of patients are needed to exclude the possibility that histologic type may provide significant prognostic information in other stages of the disease. PMID- 20573369 TI - Evidence for the role of matrix metalloproteinase-13 in bone resorption by giant cell tumor of bone. AB - Giant cell tumor of bone (GCT) is an aggressively osteolytic primary bone tumor that is characterized by the presence of abundant multinucleated osteoclast-like giant cells, hematopoietic monocytes, and a distinct mesenchymal stromal cell component. Previous work in our laboratory has shown that matrix metalloproteinase (MMP)-13 is the principal proteinase expressed by the stromal cells of GCT. The release of cytokines, particularly interleukin-1beta, by the giant cells of GCT acts on stromal cells to stimulate a surge in MMP-13 secretion. The purpose of this study was to determine the bone resorption capabilities of the cellular elements of GCT and the significance of the MMP-13 expression involved in GCT bone resorption. We present a 3-dimensional histomorphometric technique developed to analyze resorption pit depth and yield an accurate measurement of bone resorption with a direct physical view of lacunae on bone slices. In this study, we demonstrate that the mesenchymal stromal cells and the multinucleated giant cells of GCT are independently capable of bone resorption. However, coculture of these 2 cell fractions shows a synergistic increase in bone resorption. In addition, inhibition of MMP-13 reduces resorptive activity of the cells indicating that MMP-13 likely plays an important role in this tumor. This cell-cell cooperation involves giant cell-derived cytokine up regulation of MMP-13 in the stromal cells, which in turn assists the giant cells in bone resorption. Future research will involve elucidation of the role of cell cell/matrix communication pathways in bone resorption and tumorigenesis in GCT. PMID- 20573370 TI - Prognostic impact of blood vessel invasion in gastrointestinal stromal tumor of the stomach. AB - Gastrointestinal stromal tumors have a wide spectrum of biologic behavior, and occasional cases show liver metastases. The modified risk grade based on tumor size and mitotic counts has been proposed to predict the biologic behavior in gastric gastrointestinal stromal tumors. Blood vessel invasion (BVI) is important in the development of metastasis of various kinds of cancer. The aim of this study was to elucidate the potential role of blood vessel invasion in gastric gastrointestinal stromal tumors. Blood vessel invasion was found in 17 of 122 cases (13.9%) of gastrointestinal stromal tumors, and was significantly correlated with larger tumor size, higher mitotic count and higher modified risk grade. Among 83 cases of primary, localized gastric gastrointestinal stromal tumors available for follow-up information, liver metastasis was observed in 14 cases (16.9%). When blood vessel invasion was positive in the primary tumor, liver metastasis occurred in 80% of cases after the initial surgery, indicating that blood vessel invasion was a significant risk factor of liver metastasis (P < .0001). In univariate and multivariate analyses, tumor size (>5 cm), mitotic count (>5/50 high-power fields) and blood vessel invasion (positive) were significantly associated with a shorter period of disease-free survival. Our results suggest that the evaluation of blood vessel invasion may be useful for predicting the risk of liver metastasis and aggressive biologic behavior of gastrointestinal stromal tumors, and may serve as important information for determining the therapeutic strategies including adjuvant molecular target therapy. PMID- 20573371 TI - Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. AB - Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer deaths in the United States. Single-agent gemcitabine remains the standard treatment of advanced pancreatic adenocarcinoma. A recently discovered histone methyltransferase termed enhancer of zeste homologue 2 (EZH2) was found to be overexpressed in a variety of carcinomas including pancreatic adenocarcinoma. Silencing of E-cadherin was proposed as a mechanism by which enhancer of zeste homologue 2 mediates tumor aggressiveness, and enhancer of zeste homologue 2 depletion has been found to sensitize pancreatic cancer cells to gemcitabine. In this study, we correlated enhancer of zeste homologue 2 with E-cadherin expression in pancreatic adenocarcinoma and evaluated response to gemcitabine in relation to enhancer of zeste homologue 2 expression in tumor cells. Fifty-four pancreatic adenocarcinomas, 13 intraductal papillary mucinous neoplasms, and 6 chronic pancreatitis cases were stained with antibodies against enhancer of zeste homologue 2 and E-cadherin. Enhancer of zeste homologue 2 staining was scored from 1 to 4+ and classified as either low (1-2+ in <25% of tumor nuclei) or high (3-4+ in >25% of tumor nuclei). E-cadherin expression was scored on membrane positivity as follows: 0 (0%-10%), 1 (10%-25%), 2 (25%-75%), and 3 (>75%). High enhancer of zeste homologue 2 expression in pancreatic adenocarcinoma was significantly associated with decreased E-cadherin expression and more aggressive disease. There was significantly longer survival in gemcitabine-treated patients with low versus high enhancer of zeste homologue 2 expression. High enhancer of zeste homologue 2 expression was detected in intraductal papillary mucinous neoplasms with moderate to severe dysplasia, but not in chronic pancreatitis. Our study suggests that E-cadherin down-regulation may lead to enhancer of zeste homologue 2-mediated invasion and metastasis. PMID- 20573372 TI - Mesothelin (MSLN) promoter is hypomethylated in malignant mesothelioma, but its expression is not associated with methylation status of the promoter. AB - Gene methylation leads to malignant progression in some tumors. The mechanism by which mesothelin is expressed in malignant mesothelioma (MM) is not well understood. MM is histologically divided into 3 subtypes, that is, the epithelioid, sarcomatoid, and biphasic types, and it was shown that mesothelin expression was restricted to the epithelioid type and the epithelioid component of the biphasic type of MM. However, its regulatory mechanism of expression has not been clarified. Here, we studied the expression of mesothelin by immunohistochemistry along with the methylation status of 20 CpG sites in the promoter of the mesothelin gene (MSLN) in 118 lung specimens, including 39 MM, 41 lung carcinoma, 26 nonneoplastic pulmonary lesions, and 12 normal lung tissue samples by the methylation-sensitive single nucleotide primer extension technique. We confirmed that mesothelin was expressed in the epithelioid type and epithelioid component of the biphasic type of MM but neither in the sarcomatoid type nor sarcomatous component of the biphasic type. Surprisingly, the MSLN promoter was significantly hypomethylated in the MM cases regardless of its subtype, compared with the other pulmonary lesions and normal lung tissue samples. These findings suggested that hypomethylation of the MSLN promoter may be specifically associated with the formation of MM, regardless of its expression status, and that the expression of mesothelin protein was lost in the sarcomatoid type by some unknown posttranscriptional regulatory mechanism. We also identified 4 CpG sites, among the 20 sites studied, to be more specifically hypomethylated in MM cases. PMID- 20573373 TI - Rete testis invasion by malignant germ cell tumor and/or intratubular germ cell neoplasia: what is the significance of this finding? AB - Pathologic stage and postsurgical treatment guidelines of malignant germ cell tumors, currently take into account angiolymphatic invasion, degree of extra testicular invasion, and serum tumor marker levels. The significance of rete testis invasion by malignant germ cell tumors or intratubular germ cell neoplasia however remains controversial. A search through the surgical pathology and expert consultation files at our institution from 2002 to 2009 was made for malignant germ cell tumors and intratubular germ cell neoplasia in orchiectomy specimens. Clinicopathologic data including rete testis status were obtained. Two hundred ninety-two orchiectomy specimens were identified. One hundred thirty-six were associated with malignant germ cell tumors. Mean patient age was 33 years (range, 14-67 years). The mean greatest tumor dimension was 4.1 cm (range, 0.8-18 cm). Fifty-six were pure seminoma (40%), 50 were nonseminomatous malignant germ cell tumors (35%), and 35 were mixed malignant germ cell tumors including a seminoma component (25%). Intratubular germ cell neoplasia was identified in 99 cases (70%). Pathologic stage at presentation was as follows: stage 1, 71 patients (50%); stage 2, 62 patients (45%); stage 3, 2 patients (1%); and indeterminate, 6 patients (4%). Seventy-eight patients had documented rete testis status: rete testis invasion, 41 (53%); no rete testis invasion, 37 (47%). Angiolymphatic invasion was present in 62 cases (44%). Follow-up information was available in 43 patients with known rete testis status. Mean follow-up duration was 43 months (range, 3-65 months). Twenty patients had rete testis invasion, and 23 patients had no rete testis invasion. Intratubular germ cell neoplasia was present in patients with rete testis invasion in 18 cases (90%), compared to only 13 cases (57%) in patients without rete testis invasion, P = .02. Serum markers were elevated in 10 patients (50%) with rete testis invasion compared to only 6 patients (26%) without rete testis invasion, P = .05. The combination of rete testis invasion and angiolymphatic invasion were present in 8 cases and were found to be associated with elevated serum tumor markers in 7 (88%) of the 8 cases, compared to the combination of no invasion of the rete testis and angiolymphatic invasion showing elevated serum tumor markers in 3 (38%) of 8 cases. However, 7 patients (35%) with rete testis invasion developed metastatic disease, and 11 patients (48%) without rete testis invasion developed metastatic disease. Rete testis status should be documented in orchiectomy specimens with malignant germ cell tumors. Intratubular germ cell neoplasia may be the only component of a malignant germ cell tumor involving the rete testis. In this series, elevated tumor markers were more likely associated with angiolymphatic invasion and positive rete testis status. Positive rete testis status does not appear to be an independent predictor of patient outcome. PMID- 20573374 TI - Interobserver variability in the evaluation of mismatch repair protein immunostaining. AB - Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein staining. Full consensus was achieved in 51% of the stainings for MLH1, 61% for PMS2, 83% for MSH2, and 45% for MSH6. Weak stainings were the main cause of reduced consensus, whereas contradictory evaluations with normal as well as loss of staining were reported in 2% to 6% of the tumors. Interobserver variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance in hereditary nonpolyposis colorectal cancer, the interobserver variability identified highlights the need for quality assessment programs, including guidelines for classification of different expression patterns. PMID- 20573375 TI - Mutational and expressional analysis of RFC3, a clamp loader in DNA replication, in gastric and colorectal cancers. AB - Parts of gastric (GC) and colorectal cancers (CRC) exhibit microsatellite instability (MSI) that causes frameshift mutations and contributes to cancer development. DNA replication and repair play crucial roles in maintenance of genome stability, and their alterations contribute to cancer development. In this study, we analyzed mutation of RFC1 and RFC3, clamp loaders in DNA replication, in GC and CRC with MSI. We analyzed mononucleotide repeats in RFC1 and RFC3 in 29 GC with high MSI (MSI-H), 20 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 35 CRC with MSI-H, 20 CRC with MSI-L, and 45 CRC with MSS by single-strand conformation polymorphism. We also analyzed RFC3 expression in the GC and CRC. We found RFC3 frameshift mutations in 7 GC (24.1%) and 9 CRC with MSI-H (25.7%) but not in cancers with MSI-L or MSS. The mutations consisted of 14 c.244delA, one 243_244delAA, and one c.244dupA, which would result in premature stops of RFC3 amino acid synthesis. Loss of RFC3 expression was observed in 51% of the GC and 65% of the CRC, but all of the cancers with RFC3 frameshift mutations were weak or negative. Our data indicate RFC3 mutation and loss of RFC3 expression occur in large fractions of GC and CRC and suggest that these alterations may contribute to the cancer pathogenesis by deregulating DNA repair and replication. PMID- 20573376 TI - The Early-Middle Pleistocene environmental and climatic change and the human expansion in Western Europe: A case study with small vertebrates (Gran Dolina, Atapuerca, Spain). AB - The dispersal of hominins may have been favored by the opening of the landscape during the Early-Middle Pleistocene transition (EMP) in Western Europe. The structure of the small-vertebrate assemblages of the archaeo-paleontological karstic site of Gran Dolina in Atapuerca (Burgos, Spain) shows important environmental and climatic changes in the faunal succession, across the Matuyama Brunhes boundary at 780 ka. These changes are interpreted to indicate impoverishment of the forests, along with an increase in dry meadows, and open lands in general that entailed a tendency towards the loss of diversity in small vertebrate communities above the EMP. We evaluate variation in diversity of the faunal succession of Gran Dolina using Shannon's Second Theorem as an index of ecosystem structure. The long cultural-stratigraphic sequence of Gran Dolina during the EMP is somewhat similar in its completeness and continuity to that in the locality of Gesher Benot Ya'aqov in the Upper Jordan Valley. We also evaluate related data including faunal and floral (pollen) succession. Both localities present cold, dry and humid, warm fluctuations at the transition between the Early and the Middle Pleistocene. Comparisons between these sites present opportunities to understand large-scale climatic changes. PMID- 20573377 TI - Comparison of validated instruments measuring sexual function in men. AB - OBJECTIVES: There is no universally accepted instrument to measure sexual function (SF) in men. We compare validated SF measures in a single cohort. METHODS: We compare the Sexual Health Inventory for Men (SHIM), Expanded Prostate Cancer Index Composite SF domain (EPIC-SF), and a reconstructed University of California Los Angeles Prostate Cancer Index SF domain (PCI-SF) in 856 men scheduled for radical prostatectomy. We define potency thresholds for the PCI-SF and EPIC-SF. RESULTS: Mean age, body mass index, Gleason sum, and PSA were 57 years, 26.7 kg/m(2), 6.3, and 5.9 ng/mL, respectively. Mean instrument scores were as follows: SHIM 20.1; EPIC-SF 65; PCI-SF 71. All instruments were significantly intercorrelated (r = 0.99 for EPIC-SF vs PCI-SF, r = 0.75 for SHIM vs EPIC-SF, r = 0.77 for SHIM vs PCI-SF, all P < .001). The SHIM had the greatest negative skew and ceiling effect (P < .001). Although high scores on either the EPIC-SF or PCI-SF translated reliably to high SHIM scores, the reverse was not true. Subjects who reported no erectile dysfunction (ED) on the SHIM (>or=22) had diverse overall SF, whereas those who scored highly on the EPIC-SF or PCI-SF had both excellent erectile function (potency) and overall SF (including orgasmic function, erectile function, and sexual desire). EPIC-SF scores >or=65 and PCI-SF scores >or=75 define men that are both potent and have good SF. CONCLUSIONS: The SHIM is intended as an instrument to assess ED. It is, however, inadequate as a measure of overall SF. The EPIC-SF and PCI-SF capture gradations of both sexual and erectile function and may also be used to define potency more comprehensively. PMID- 20573378 TI - Ocular complications after open and hand-assisted laparoscopic donor nephrectomy. AB - OBJECTIVES: To compare the incidence of ocular complications (OC) and corneal abrasion (CA) after hand-assisted laparoscopic donor nephrectomy (HALDN) and open donor nephrectomy (ODN). METHODS: A retrospective review was conducted of 241 consecutive patients (141 HALDN and 100 ODN) over a 9-year period. OC were strictly defined as ocular complaints requiring any treatment or ophthalmologic consultation. Chi-square tests were used to compare the incidence of OC and CA by type of surgery. RESULTS: OC were observed in 9 HALDN patients (6.4%) and no ODN patients (0%; P = .01). All OC in HALDN patients involved the dependent eye (P <.001). CA occurred in 2 HALDN patients (1.4%) compared with no ODN patients (0%; P = .23). HALDN patients had significantly higher net fluid intake than the ODN patients (P <.01). CONCLUSIONS: The increased OC and CA seen in HALDN patients may result from the increased fluid intake, flank positioning, and potential increased venous compression resulting from the effects of the pneumoperitoneum. The fact that the dependent eye was involved in all patients suggests conjunctival edema as a potential common pathway. The high frequency of OC suggests the importance of techniques to minimize OC after HALDN. PMID- 20573379 TI - Identification and management of emptying failure in male patients with orthotopic neobladders after radical cystectomy for bladder cancer. AB - OBJECTIVE: To treat neobladder emptying failure after radical cystectomy in patients with bladder cancer. The etiology of neobladder emptying failure should be identified. METHODS: We analyzed the outcome of neobladder emptying in 231 male patients who received neobladder reconstruction after radical cystectomy. The clinical characteristics, urodynamic evaluation, and treatment information were collected from all patients with emptying failure. RESULT: The total occurrence of neobladder emptying failure was 37 of 231 (16%). Emptying failure was a result of mechanical obstruction in 25 (10.8%) patients; obstructions were caused by strictures of the neobladder-urethral anastomosis (13 cases, 5.6%), anterior urethral strictures (3 cases, 1.2%), obstructive mucosal valves (2 cases, 0.9%), primary cystolithiasis (1 case, 0.4%), mucus plugs (2 cases, 0.9%), urethral tumor recurrence (2 cases, 0.9%), and pelvic tumor recurrence (2 cases, 0.9%). In 21 of 25 patients with mechanical obstructions, bladder function was completely recovered via an endourological approach. However, in 12 of patients with dysfunctional voiding, 3 patients presented higher compliance of neobladder. Two patients were found with a narrower posterior urethral angle. Eventually, 10 patients of 12 with dysfunctional voiding performed intermittent self catheterization. CONCLUSIONS: The obstructive outlet was the primary cause of emptying failure in neobladders. Most of the patients with mechanical obstructions could obtain satisfactory neobladder emptying by a minimally invasive surgical approach. However, nearly all the patients with dysfunctional voiding will have to receive clean intermittent catheterization until the mechanisms causing failure are better understood. PMID- 20573380 TI - TUNEL as a test for sperm DNA damage in the evaluation of male infertility. AB - OBJECTIVES: To standardize the TUNEL assay by establishing inter- and intraobserver variability, interassay variability, cutoff values, sensitivity and specificity of the assay, and studying the distribution of the DNA damage in a population of infertile men referred to a clinical andrology laboratory. METHODS: Seminal ejaculates from 25 healthy male volunteers (controls) and 194 infertile men (with male factor infertility) referred to an andrology laboratory were examined for DNA damage by TUNEL assay using flow cytometric analysis. RESULTS: Both the inter- and intraobserver variability and interassay variability was small (<10%). DNA damage in the controls was 11.9 +/- 6.8% vs. 29.5 +/- 18.7% in patients (P <.001). The cut-off value of 19.25% maximized the observed sensitivity (64.9%) and specificity (100%) of the assay. The distribution of DNA damage in the patients was as follows: 14.9% (29 of 194) with DNA damage between 0% and 10%; 22.7% (44 of 194) between 10% and 20%; 8.8% (17 of 194) between 20% and 30%; and 17.5% (34 of 194) between 30% and 40%. Finally, 27.3% (53 of 194) had TUNEL values >40%. CONCLUSIONS: We report a detailed standardization of the TUNEL assay for clinical use, as well as reference ranges for DNA damage in normal healthy donors and infertile men. A cut-off of 19.25% with observed 100% specificity established in our program can differentiate infertile men with DNA damage from healthy men. This test can be offered to infertile patients who are idiopathic, have severe oxidative stress-related abnormal semen quality, and contribute to the infertility problem of the couple who are considering assisted reproductive techniques. PMID- 20573381 TI - Epididymal reflux in posterior urethral valves. AB - We report the findings of voiding cystourethrography in a boy with posterior urethral valves that showed reflux into the epididymis. PMID- 20573382 TI - Higher body mass index is associated with lower risk of prostate cancer detection via multi (>= 12)-core prostate biopsy in Korean men. AB - OBJECTIVES: To investigate the potential effect of body mass index (BMI) on prostate cancer detection among Korean men who underwent prostate biopsy via contemporary multi (>= 12)-core approach. METHODS: We reviewed records of 3113 Korean men who underwent initial multi (>= 12)-core prostate biopsy at our institution. Variables including age, prostate-specific antigen (PSA), digital rectal exam (DRE) finding, prostate volume, and biopsy outcomes were analyzed with respect to BMI. Multivariate logistic and linear regression analysis was applied to examine the association between BMI and detection of prostate cancer (or high-grade diseases) on prostate biopsy, adjusting for age, prostate volume, PSA, and DRE finding. RESULTS: Among 3113 subjects, BMI was >= 30 kg/m(2) in only 45 (1.4%). Overall, 1071 (34.4%) patients had a positive biopsy. In multivariate analysis incorporating variables of age, BMI, PSA, DRE finding, and prostate volume, BMI >= 25 kg/m(2) was significantly associated with lower odds of prostate cancer detection via biopsy among our subjects (odds ratio = 0.76, P = .002). Also, BMI >= 25 kg/m(2) was significantly associated with lower rate of high-grade (Gleason score >= 4 + 3) diseases detected from biopsy, also after multivariate adjustment (odds ratio = 0.69, P = .007). CONCLUSIONS: Higher BMI was associated with lower risk of detection of prostate cancer, including high grade cancer, among Korean men who are generally leaner than Westerners, undergoing contemporary multicore prostate biopsy, independent of patient age, PSA, DRE finding, and prostate volume. PMID- 20573383 TI - Ultrasound-guided minimally invasive percutaneous nephrolithotomy in flank position for management of complex renal calculi. AB - OBJECTIVES: To evaluate the safety and efficacy of performing ultrasound-guided minimally invasive percutaneous nephrolithotomy (MPCNL) in the flank position for the management of complex renal calculi. Percutaneous nephrolithotomy is usually performed with the patient in the prone position under fluoroscopic guidance; however, this position, and guidance method have some limitations. METHODS: From January 2007 to December 2009, 93 patients (101 kidneys) with complex renal calculi underwent ultrasound-guided MPCNL in the flank position. RESULTS: The mean age of the patients was 45.3 years (range 29-71). The calculi-free rate in the patients who underwent a single procedure was 78.2% (79 of 101 kidneys). The average operative duration was 82.6 minutes (range 45-190). Although the perioperative blood loss was not significantly different between single-tract and double-tract MPCNL (P = .087, F = 2.981), the calculi-free rate was significantly greater in the patients who underwent double-tract MPCNL than in those who underwent single-tract MPCNL (P = .027, chi-square = 4.873). Perioperative blood transfusions were not required in any patient. Similarly, ureteral calculi due to percutaneous nephrolithotomy were not observed. Secondary renal hemorrhage occurred in 3 patients who had undergone single-tract MPCNL and 1 underwent nephrectomy. CONCLUSIONS: The results of our study have shown that ultrasound guided MPCNL with the patient in the flank position is safe and effective for treating complex renal calculi, without the side effects of radiation to the patient and surgeon. Double-tract MPCNL is suitable for complex renal calculi and, in some cases, is required to increase the calculi-free rate. The insertion of twin ureteral catheters before lithotripsy might be helpful in avoiding residual ureteral calculi after percutaneous nephrolithotomy. PMID- 20573384 TI - A comparison of outcomes for interfascial and intrafascial nerve-sparing radical prostatectomy. AB - OBJECTIVE: To compare the outcome of intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy (nsEERPE) with interfascial (standard) nsEERPE. METHODS: Four-hundred patients underwent nsEERPE; 200 patients underwent bilateral intrafascial nsEERPE (group A) and 200 bilateral standard nsEERPE (group B). Tumor stages of T1 and T2a, prostate-specific antigen level <10 ng/mL, maximal Gleason score 3+4 (not 4+3) and preoperative potency were considered as candidates for nsEERPE. Patients were randomized to the aforementioned groups. Perioperative data, and functional and oncological outcome were reviewed. Patients not requiring any pads or requiring 1 pad for safety were defined as continent. Patients responding positively to sexual encounter profile diary question numbers 2, 3, and 5 were considered as potent. RESULTS: Perioperative data were similar between groups. At 3 months, 74% of group A and and 63% of group B were continent. At 6 months, the respective figures were 87.9% and 76.2%, respectively (A, B). At 12 months, 93.2% of group A and 90.7% of group B were continent. Potency rates of group A were 93.5% (<55 years), 83.3% (55-65 years), and 60% (>65 years) at 12 months. The respective figures for Group B were 77.1%, 50%, and 40%. Positive surgical margins were detected in 9% and 9.5% of groups A and B, respectively. CONCLUSIONS: Intrafascial nsEERPE provides significantly better potency in patients <55 years of age at 12 months and in patients 55-65 years of age at 6 and 12 months, with probably limited effect on the oncological outcome. Significantly improved continence was observed at 3 and 6 months in favor of intrafascial nsEEPRE. PMID- 20573385 TI - Flexible ureterorenoscopy with holmium laser in horseshoe kidneys. AB - OBJECTIVES: To assess the outcome of flexible ureterorenoscopy (F-URS) with the holmium laser in treating stones in the horseshoe kidney (HSK). METHODS: We retrospectively reviewed the records of 17 patients with a HSK stone (17 renal units) who had undergone F-URS with the holmium laser from December 2004 to May 2009. The presenting symptoms were renal colic, urinary tract infection, or hematuria. F-URS was used in as an alternative after the failure of shock wave lithotripsy in 8 patients (47%) and percutaneous nephrolithotomy failure in 4 patients (23.5%). Follow-up examination was performed after 4-6 weeks with plain radiography and either renal ultrasonography or noncontrast computed tomography. Success was defined as stone-free status or residual fragments <3 mm. The use of auxiliary procedures was considered to indicate treatment failure. RESULTS: A total of 17 patients were included in the present study (3 females and 14 males). Their age was 16-52 years (mean age +/- SD 34.7 +/- 6.3). The HSK stone location was 7 mixed caliceal, 3 mixed pelvic and caliceal, and 7 pelvic. The average stone burden was 16 mm (range 7-35). The overall number of procedures was 25 (mean 1.5 procedures/patient). Of the 17 patients, 15 (88.2%) were rendered stone free. CONCLUSIONS: The results of our study have shown that F-URS with the holmium laser is an efficient minimal invasive procedure for treating HSK stones. PMID- 20573387 TI - The pediatric renal clear cell "sugar" tumor: pseudo-alveolar structure mimicking clear cell renal carcinoma. AB - The primary extrapulmonary sugar tumor (PEST) is rare. Up to now, only 16 cases of PEST have been reported, including 5 pediatric cases. We report a renal benign PEST in a 16-year-old boy, which is the first such case to be reported in the pediatric kidney. The tumor was composed of clear and eosinophilic epithelioid cells, growing with nest and pseudoalveolar structure, which can be confused with renal clear cell carcinoma. The tumor cells were positive for melanocytic and negative for epithelial markers. The tumor was enucleated, and the patient was well without recurrence 21 months after surgery. PMID- 20573386 TI - Prevalence and impact of bacteriuria and/or urinary tract infection in interstitial cystitis/painful bladder syndrome. AB - OBJECTIVES: To determine the prevalence and clinical significance of documented bacteriuria and/or urinary tract infection in an interstitial cystitis/painful bladder syndrome (IC/PBS) population. METHODS: Urine cultures were obtained at the initial assessment (documentation of sterile urine mandatory at diagnosis) and during routine follow-up, at each active treatment visit, and during and after the presentation and treatment of symptom flares in consecutively assessed female patients with IC/PBS. At each visit, the following questionnaires were completed: the O'Leary-Sant IC Symptom and Problem Index, the Pain Urgency Frequency questionnaire, and pain, frequency, and urgency Likert scales (0-10). RESULTS: A total of 100 patients with IC were followed up for 2 years. Of these 100 patients, 31 (31%) had >= 1 documented positive urine culture with a traditional uropathogen (mean 1.8, range 1-5). No difference was seen in the patients identified with bacteriuria and those without bacteriuria in age, symptom duration, O'Leary-Sant IC Symptom and Problem Indexes, Pain Urgency Frequency questionnaire, or pain, frequency, and urgency Likert scales. No correlation was found between the number of bacteriuria episodes and any symptom index evaluated. No significant difference was seen in any of the symptom indexes evaluated at baseline, during the bacteriuria episodes, or after successful bacterial eradication in the group identified with bacteriuria. CONCLUSIONS: The presence of bacteriuria can be documented in an IC/PBS population of women whose urine has frequently been cultured; however, the patients with bacteriuria did not differ from those without evidence of bacteriuria, the bacteriuria episodes did not appear to be associated with the symptom flares, and antibiotic treatment of documented bacteriuria was not associated with significant IC/PBS-related symptom amelioration. PMID- 20573388 TI - Expression of Ki-67 and COX-2 in patients with upper urinary tract urothelial carcinoma. AB - OBJECTIVES: To investigate the prognostic value of Ki-67, cyclooxygenase-2 (COX 2), E-cadherin, and retinoblastoma protein (pRB) in patients with urothelial carcinoma of the upper urinary tract. METHODS: From January 1998 to December 2005, the specimens from 107 patients with urothelial carcinoma of the upper urinary tract who had undergone nephroureterectomy were analyzed. The expression of Ki-67, COX-2, E-cadherin, and pRB was examined by immunochemistry on tissue microarray sections. The correlation of the immunoreactivity with the pathologic parameters and progression-free and cancer-specific survival were examined. RESULTS: Ki-67 and COX-2 were overexpressed in 26 (24%) and 38 patients (36%), respectively. The loss of E-cadherin expression was observed in 66 patients (62%). Altered pRB expression was found in 37 patients (34%). Overexpression of Ki-67 (P = .041 and P = .006, respectively) and COX-2 (P = .002 and P = .001, respectively) was associated with the pathologic stage and grade. Multivariate analysis showed that Ki-67 overexpression (P = .002), T stage (P = .009), and lymph node metastases (P = .009) were independent predictors of progression-free survival. In addition, Ki-67 overexpression (P = .007) and pathologic T stage (P = .003) were independent predictors of cancer-specific survival. No association was found between the pathologic findings and prognosis and the other markers (E cadherin and pRB). CONCLUSIONS: Our results suggest that Ki-67 overexpression is an independent predictor of the progression of urothelial carcinoma of the upper urinary tract. Patients with Ki-67 overexpression should be followed up more closely. In addition, they might be candidates for future prospective therapy trials. PMID- 20573389 TI - Years of potential life lost and productivity losses from male urogenital cancer deaths--United States, 2004. AB - OBJECTIVES: To estimate years of potential life lost (YPLL) and productivity losses due to deaths from male urogenital cancers in the United States in 2004. METHODS: To estimate YPLL, we applied a life expectancy method using 2004 national mortality data and life tables. To estimate lifetime productivity losses, we used human capital approach accounting for both the market value and the imputed value of housekeeping services. We calculated results for age and racial/ethnic groups and for 8 categories of male urogenital cancers. RESULTS: In 2004, deaths from urological cancers accounted for 244,080 YPLL, with an average of 14.4 YPLL per death, and deaths from genital cancers accounted for 309,921 YPLL, with an average of 10.5 YPLL per death. Kidney cancer accounted for 42.7% YPLL from male urological cancers, and prostate cancer accounted for 94.2% of the YPLL from male genital cancers. Testicular cancer had the highest average number of YPLL per death (37.9). Non-Hispanic whites accounted for 77.9% of the YPLL from male urogenital cancer deaths. Overall, urogenital cancers had the largest relative contribution to YPLL among men aged >=50 years. In 2004, the estimated lifetime productivity loss because of deaths from male urogenital cancer was $10.4 billion USD, 10.6% of the estimated $97.9 billion USD loss because of deaths from all cancers among US men. CONCLUSIONS: Urogenital cancers impose a considerable health and economic burden in terms of premature deaths and productivity losses in men in the United States, particularly among the elderly and non-Hispanic whites and blacks. PMID- 20573390 TI - Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy. AB - OBJECTIVES: Pyruvate kinase type M2 (TuM2-PK) and thymidine kinase 1 (TK1) are the key enzymes involved in tumor cells metabolism and proliferation. We explored the association of their preoperative circulating levels with disease recurrence in patients with renal cell carcinoma (RCC). METHODS: We measured the plasma levels of TuM2-PK levels and serum TK1 activity preoperatively in patients with RCC, using a quantitative ELISA, and correlated the results with clinicopathological parameters. RESULTS: Significantly higher levels of TuM2-PK and TK1 were found in 116 patients with RCC compared with 20 healthy participants (P < .001 and P = .03), but not compared with 27 patients with benign kidney tumors (P = .13 and P = .72). There was a significant association between the level of TuM2-PK and of TK1 activity with T stage (P = .01 and P = .04). Of 2 markers only TuM2-PK was significantly associated with tumor grade (P = .001). The presence of extensive tumor necrosis (> 50%) was associated with high TuM2-PK (P = .001) and low TK1 (P = .03). The 5-year recurrence-free survival for patients with elevated TuM2-PK or TK1 was significantly lower compared with those for patients with normal marker levels (55% vs 94%, P < .001 and 21% vs 90%, P = .002). Multivariate Cox Proportional Hazard analysis demonstrated that TuM2-PK and TK1, adjusted for stage, grade and tumor necrosis were retained as independent predictors of disease recurrence (HR = 7.3, P = .04 and HR = 3.8, P = .03). CONCLUSIONS: The measurements of 2 circulating biomarkers, TuM2-PK and TK1, in RCC patients before nephrectomy can be useful for predicting recurrence and stratifying the patients into risk groups for possible adjuvant treatment. PMID- 20573391 TI - The prenatal diagnosis of Beckwith-Wiedemann syndrome using ultrasound and magnetic resonance imaging. AB - Beckwith-Wiedemann syndrome is a rare congenital overgrowth syndrome. It carries important connotations for the pediatric urologist because it is associated with an increased risk for developing certain embryonal tumors. Until recently, these patients were not diagnosed until after birth; however, with newer imaging modalities, this syndrome may be diagnosed prenatally. We present a case of Beckwith-Wiedemann syndrome, depicting the prenatal modalities that may be used to diagnose this unusual condition. PMID- 20573392 TI - The National Cancer Database report on advanced-stage epithelial ovarian cancer: impact of hospital surgical case volume on overall survival and surgical treatment paradigm. AB - OBJECTIVE: To examine the effect of hospital procedure volume and other prognostic variables on overall survival outcome and likelihood of receiving standard recommended care among patients with advanced-stage epithelial ovarian cancer. METHODS: The National Cancer Data Base (NCDB) was searched for patients undergoing primary treatment for FIGO Stage IIIC/IV epithelial ovarian cancer from 1996 to 2005. The average annual surgical procedure volume was derived for each reporting hospital. Quartile ranking discriminated four groups of hospitals based on annual surgical volume: low (<9), intermediate (9-20), high (21-35), and very high (>35). Cox proportional hazards modeling was used to determine the impact on overall survival of hospital surgical volume adjusted for treatment, FIGO/AJCC stage, ethnicity, age, payer status, household income, and tumor grade. Binomial multivariate logistic regression modeling was used to assess differences in patient demographic, tumor, and treatment variables between high/very high volume hospitals and low/intermediate volume hospitals. RESULTS: A total of 45,929 patients were identified. After adjusting for other factors, overall survival was significantly correlated with hospital case volume: very high (reference); high (HR 0.98, 95% CI=0.92-1.04); intermediate (HR 1.08, 95% CI=1.01 1.15); and low (HR 1.14, 95% CI=1.07-1.22). Compared to low and intermediate volume hospitals, patients treated at very high and high-volume hospitals were less likely to receive neo-adjuvant chemotherapy (OR=0.33, 95% CI=1.18-1.50) or surgery alone (OR=0.77, 95% CI=0.73-0.82) instead of initial surgery and adjuvant chemotherapy. CONCLUSIONS: Hospital ovarian cancer surgical volume >or=21 cases/year is associated with a higher likelihood of patients with Stage IIIC/IV epithelial ovarian cancer receiving standard treatment (surgery followed by adjuvant chemotherapy). Even after adjusting for treatment paradigm and other factors, hospital volume >or=21 cases/year was significantly predictive of improved overall survival outcome. PMID- 20573394 TI - Surface morphology optimization for osseointegration of coated implants. AB - This paper aims to establish a relationship between the surface morphology induced micromechanics and bone remodeling responses to a solid bead coated porous implant and further to develop a multiobjective optimization framework for the coating design of biomaterials. Multiscale modeling and remodeling techniques were developed, where a macroscopic analysis was initially performed to generate a global response to enable a microscopic analysis. The bone remodeling responses of the microscopic models (with a specific surface morphology) were evaluated in terms of the average apparent density developed in the peri-implant region. To explore the proposed multiscale analysis and design methods, a typical dental implantation setting is exemplified in this study. The response surface method (RSM) was utilized to relate the major implant coating parameters to the bone responses. It is found that increasing the volume fraction of the coating beads/particles results in a greater bone density, whereas increasing bead/particle size does not significantly affect the bone's responses. Several different multiobjective optimization schemes were adopted to optimize the coated bead size and volume fraction, which reveal that the optimal design parameters of particle diameter and volume fraction are 100 microm--35% and 38 microm--17.5% for the cortical and cancellous bones respectively, agreeing with clinical data. To maximize the implant/bone interfacial stability, specific surface coating designs for particular locations are recommended. PMID- 20573395 TI - Preservation of dendritic cell function upon labeling with amino functionalized polymeric nanoparticles. AB - Dendritic cells (DCs) are key players in eliciting immunity against antigens, therefore making them the focus of many investigations on immune responses in infections, cancer and autoimmune diseases. Nanosized materials have just recently been investigated for their use as carriers of antigens and as labeling agents for DCs. For this later use nanoparticles should be non-toxic and should most importantly not alter the physiological functions of DCs. Here we demonstrate that by the use of polymeric fluorescent nanoparticles as synthesized by the miniemulsion process immature DCs (iDCs) can be efficiently labeled intracellularly. Amino functionalized nanoparticles are more effective than carboxy functionalized ones. Even after 8 days 95% of DCs have retained nanoparticles with a fluorescence intensity of 67% compared to day 1. Nanoparticle labeling does not influence expression of cell surface molecules on mature DCs (mDCs) like HLA-DR, CD80/83/86, CCR7, CD11c nor does it influence the immunostimulatory capacity of mDCs. This procedure does also not impair the capability of DCs for uptake, processing and presentation of viral antigens as demonstrated by interferon-gamma ELISPOT on T cells stimulated with viral antigens presented by DCs. Therefore polymeric nanoparticles are a promising tool to study migration and homing of DCs in animal studies. PMID- 20573393 TI - Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration. AB - Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of regenerated tissue. HA hydrogels were designed to degrade at fast, intermediate, and slow rates due to hydrolysis and further provided controlled release of cationic proteins due to electrostatic interactions. Scaffolds delivering bone morphogenetic protein-2 (BMP-2) were evaluated in a rat calvarial bone critical size defect model. BMP-2 delivery from the HA hydrogels had a clear osteoinductive effect in vivo and, for all hydrogel types, BMP-2 delivery resulted in significant mineralization compared to control hydrogels. The temporal progression of this effect could be modulated by altering the degradation rate of the scaffold. All three degradation rates tested resulted in similar amounts of mineral formation at the latest (six week) time point examined. Interestingly, however, the fastest and slowest degrading scaffolds seemed to result in more organized bone than the intermediate degrading scaffold, which was designed to degrade in 6-8 weeks to match the healing time. Additionally, healing could be enhanced by co-delivery of vascular endothelial growth factor along with BMP-2. PMID- 20573396 TI - Biphenyl ethers conjugated CdSe/ZnS core/shell quantum dots and interpretation of the mechanism of amyloid fibril disruption. AB - The biphenyl ethers (BPEs) are the potent inhibitors of TTR fibril formation and are efficient fibril disrupter. However, the mechanism by which the fibril disruption occurs is yet to be fully elucidated. To gain insight into the mechanism, we synthesized and used a new QD labeled BPE to track the process of fibril disruption. Our studies showed that the new BPE-QDs bind to the fiber uniformly and has affinity and specificity for TTR fiber and disrupted the pre formed fiber at a relatively slow rate. Based on these studies we put forth the probable mechanism of fiber disruption by BPEs. Also, we show here that the BPE QDs interact with high affinity to the amyloids of Abeta(42), lysozyme and insulin. The potential of BPE-QDs in the detection of senile plaque in the brain of transgenic Alzheimer's mice has also been explored. PMID- 20573397 TI - p53 and autophagy contribute to dasatinib resistance in primary CLL lymphocytes. AB - B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and there is no cure for the disease. Although dasatinib is cytotoxic to primary CLL lymphocytes in vitro, the drug has been shown to be active in a small percent of CLL patients. Our previous results suggest that dasatinib targets del17 CLL lymphocytes which are the CLL patients with the worst prognosis. Here we present mechanistic evidence that dasatinib induces endoplasmic reticulum stress and autophagy in CLL lymphocytes. Furthermore we provide evidence suggesting that autophagy mediates resistance to the drugs, process that is modulated by p53. PMID- 20573398 TI - The lower risk MDS patient at risk of rapid progression. AB - Most patients with myelodysplastic syndrome (MDS) are classified at diagnosis as having a low/INT-I or INT-II/high risk disease, based on the classical International Prognostic Scoring System (IPSS) criteria. The low/INT-I risk patients are usually managed mildly with supportive care, including red blood cell (RBC) transfusions, erythroid stimulating agents (ESAs), other cytokines (G CSF, platelet stimulating agents), as well as thalidomide and lenalidomide. Some patients receive immunosuppressive therapy, and iron chelation is indicated in iron overloaded patients. Aggressive approach (hypomethylating agents, chemotherapy and stem cell transplantation) is usually not applied in such patients. Occasionally, we observe a "low risk" patient with rapid progression of disease and poor outcome. Can we identify demographic, clinical, laboratory, cellular-biological and/or molecular parameters that can predict "poor prognostic features" (PPF) in "low risk" MDS patients? Clinical and laboratory parameters have been reported to be associated with poor prognosis, in addition to the known "classical" IPSS criteria. These include older age, male gender, poor performance status, co-morbidities, degree of anemia, low absolute neutrophile count (ANC) and platelet counts, RBC transfusion requirements, high serum ferritin, high LDH, bone marrow (BM) fibrosis, increased number of BM CD34+ cells and multi-lineage dysplasia. Certain immunophenotypes (low CD11b, high HLA-Dr, CD34, CD13 and CD45), clonal granulocytes, multiple chromosomal abnormalities, chromosomal instability, short telomeres and high telomerase activity were also reported as PPF. Studies of apoptosis identified Bcl-2 expression and high caspase 3 as PPF, while the reports on survivin expression have been confusing. Recent exciting data suggest that methylation of p15 INK4b and of CTNNA1 (in 5q-), high level of methylation of other genes, absence of the TET2 mutation, down regulation of the lymphoid enhancer binding factor 1 (LEF1), mutation of the polycomb-associated gene ASXL1 and a specific 6-gene signature in gene expression profiling - are all associated with poor prognosis in MDS. Do we have data suggesting a different treatment for "low risk" MDS patients displaying PPF? Two teams, the combined Nordic-Italian and the GFM groups have reported an improved survival with ESAs. The GFM has achieved prolonged survival with iron chelation. Recently, encouraging data with survival advantage in azacitidine-treated patients have been published, including a few INT-I patients. Finally, data suggest that low/INT-I MDS patients who undergo stem cell transplantation (SCT0 do better than INT-II/high risk patients). In summary, some patients, classified as "low risk MDS" carry PPF. An appropriate therapeutic approach is indicated. Future updated classifications and prospective trials may lead to a better outcome. PMID- 20573399 TI - BCR-ABL peptide vaccination in healthy subjects: immunological responses are equivalent to those in chronic myeloid leukaemia patients. AB - We and others have reported that vaccination of chronic myeloid leukaemia (CML) patients with e14a2 BCR-ABL junctional peptides can elicit moderate but transient T cell responses. To determine whether CML patients may be tolerised to BCR-ABL, here we used the same schedule to vaccinate 5 healthy subjects. Although IFN gamma and granzyme-B production, and proliferative responses to the vaccine peptides were detected in all 5 cases, responses were statistically similar to CML patients. CML patients are therefore not appreciably tolerised to BCR-ABL, and junctional peptides may only be moderately immunogenic, underlining the importance of antigen immunogenicity when designing vaccination strategies. PMID- 20573400 TI - Glycosylation interference on RhoA activation: focus on G-CSF. AB - Glycosylation of cytokines appears to be responsible for several differences in their activity, and focusing on G-CSF, several divergences between the non glycosylated G-CSF, Filgrastim, and the glycosylated G-CSF, Lenograstim, have been reported. To verify the role of G-CSF glycosylation in mediating these differences we tested in vitro the effects on the RhoA activation of the different G-CSFs, including deglycosylated Lenograstim. The results showed that Filgrastim induced sustained-RhoA activation while Lenograstim did not do so. Deglycosylated Lenograstim mimicked Filgrastim, resulting in RhoA hyper activation. These in vitro findings demonstrate that the glycosylation of G-CSF plays a crucial role in RhoA activation. PMID- 20573401 TI - The changes in some biochemical parameters in Zea mays cv. "Martha F1" treated with atrazine. AB - In this study, Zea mays cv. "Martha F1" plant was treated with post-emergence atrazine in a concentration range of 27-226mM. The effects of post-emergence atrazine treatments upon peroxidase, ascorbate peroxidase, and lipid peroxidation were investigated on the 1st, 5th, 10th, and 15th days following the treatment. In the treatment groups, peroxidase activity and malondialdehyde (MDA) content decreased after the 10th day, while ascorbate peroxidase activity was observed to decrease on the 15th day. PMID- 20573402 TI - The combination of gene perturbation assay and ChIP-chip reveals functional direct target genes for IRF8 in THP-1 cells. AB - Gene regulatory networks in living cells are controlled by the interaction of multiple cell type-specific transcription regulators with DNA binding sites in target genes. Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence binding protein (ICSBP), is a transcription factor expressed predominantly in myeloid and lymphoid cell lineages. To find the functional direct target genes of IRF8, the gene expression profiles of siRNA knockdown samples and genome-wide binding locations by ChIP-chip were analyzed in THP-1 myelomonocytic leukemia cells. Consequently, 84 genes were identified as functional direct targets. The ETS family transcription factor PU.1, also known as SPI1, binds to IRF8 and regulates basal transcription in macrophages. Using the same approach, we identified 53 direct target genes of PU.1; these overlapped with 19 IRF8 targets. These 19 genes included key molecules of IFN signaling such as OAS1 and IRF9, but excluded other IFN-related genes amongst the IRF8 functional direct target genes. We suggest that IRF8 and PU.1 can have both combined, and independent actions on different promoters in myeloid cells. PMID- 20573403 TI - Tracing antigen signatures in the human IgE repertoire. AB - Allergen recognition by IgE antibodies is a key event in allergic inflammation. In this study, the IgE IGHV repertoires of individuals with allergy to the major birch pollen allergen, Bet v 1, were analyzed over a four years period of allergen exposure by RT-PCR and sequencing of cDNA. Approximately half of the IgE transcripts represented non-redundant sequences, which belonged to seventeen different IGHV genes. Most variable regions contained somatic mutations but also non-mutated sequences were identified. There was no evidence for relevant increases of somatic mutations over time of allergen exposure. Highly similar IgE variable regions were found after four years of allergen exposure in the same and in genetically non-related individuals. Our results indicate that allergens select and shape a limited number of similar IgE variable regions in the human IgE repertoire. PMID- 20573404 TI - Gender differences in the developmental course of depression. AB - BACKGROUND: There is ample evidence for female preponderance of major depressive disorder (MDD) in adolescence and adulthood. This study examined gender differences in the developmental course (i.e., incidence, duration, number of depressive episodes, and recovery rates) of MDD in non-referred adolescents and young adults. METHODS: Data from the Oregon Adolescent Depression Project were used to examine gender differences in the developmental course of MDD. Gender differences in the onset, duration, number of depressive episode and rate of recovery from MDD were examined in a population-based sample of the same individuals (participants: N=773) during adolescence (age 14 to 17) and at age 30. RESULTS: Compared to males, females have higher incidence rates of MDD and had a more chronic course. Difference in duration of depressive episodes is marginally significant between male and female, with females having longer episodes. Lower onset age correlates significantly with more number of episodes in both genders; however, lower onset age predicts a worse course of depression only in females. LIMITATIONS: The sample was from a single region of the country and consisted mostly of White adolescents. CONCLUSIONS: Childhood depression may be a more serious risk factor for girls than for boys. PMID- 20573405 TI - Pro-inflammatory cytokine and chemokine mRNA blood level in multiple sclerosis is related to treatment response and interferon-beta dose. AB - Of 37 multiple sclerosis patients, 19 suboptimal responders were randomized to 375 (n=12) or 250ug (n=7) interferon (IFN)-beta-1b. mRNA levels of 23 cytokines, chemokines, and chemokine receptors were quantified by TaqMan low-density array (TLDA) real-time polymerase chain reaction. Better treatment responses or increased IFN-beta doses were associated with elevated IL-10 and TGF-beta and decreased CXCL10, IL-18, IFN-gamma, and TNF-alpha transcript levels. Adjusting for dose, poor treatment responses resulted in a 4-fold increase in CXCL10 and IFN-gamma expression (Mantel-Haenszel RR=3.74, p<0.0001). CXCL10 and IFN-gamma mRNA levels were reliable indicators of treatment response. TLDA can be used to tailor IFN-beta-1b therapy. PMID- 20573406 TI - Antivirals for pandemic influenza: a triumph of policy over evidence? PMID- 20573407 TI - The What and How of prefrontal cortical organization. AB - How is the prefrontal cortex (PFC) organized such that it is capable of making people more flexible and in control of their behavior? Is there any systematic organization across the many diverse areas that comprise the PFC, or is it uniquely adaptive such that no fixed representational structure can develop? Going against the current tide, this paper argues that there is indeed a systematic organization across PFC areas, with an important functional distinction between ventral and dorsal regions characterized as processing What versus How information, respectively. This distinction has implications for the rostro-caudal and medial-lateral axes of organization as well. The resulting large-scale functional map of PFC could prove useful in integrating diverse data, and in generating novel predictions. PMID- 20573408 TI - Use of chemical mixtures to differentiate mechanisms of endocrine action in a small fish model. AB - Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis. These assays can be sensitive and highly diagnostic for key mechanisms such as agonism of the estrogen and androgen receptors (ERs, ARs) and inhibition of steroid synthesis. However, most of the tests do not unambiguously identify AR antagonists. The purpose of this work was to explore the utility of a mixture test design with the fathead minnow (Pimephales promelas) for detecting different classes of EDCs including AR antagonists. Adults of both sexes were exposed via the water to EDCs with diverse mechanisms of action in the absence or presence of 17beta-trenbolone (TB), a potent AR agonist which masculinizes female fathead minnows. Similar to previous studies with the model AR antagonists flutamide and vinclozolin, exposure of females to the AR antagonist cyproterone acetate in the presence of TB decreased expression of an easily-observed masculinization response, nuptial tubercle formation. Mixture studies with TB and the model ER agonists, 17alpha ethinylestradiol and bisphenol A, also showed inhibition of tubercle formation in the females, but unlike the AR antagonists, the estrogens markedly induced synthesis of vitellogenin (VTG: egg yolk protein), particularly in males. The ER agonists also offset TB-induced depressions in plasma VTG concentrations in female fish. Additional mixture experiments were conducted with TB and triclocarban, an anti-microbial reported to enhance AR-mediated responses, or ammonia, a "negative control" with no known direct effects on HPG function. Neither chemical affected VTG status in males or females in the absence or presence of TB; however, both slightly enhanced TB-induced tubercle formation in females. Based on studies described herein and elsewhere with the fathead minnow, a TB co-exposure assay appears to be an effective approach for clearly identifying AR antagonists as well as potential EDCs with other relevant mechanisms of action. PMID- 20573409 TI - Caregivers' estimation of patients' quality of life (QoL) in Alzheimer's disease (AD): an approach using the ADRQL. AB - The purpose of this study was to describe the QoL of patients with AD (PAD) as perceived by family caregivers, and to analyze the correlates of such QoL. This study covered 92 PAD enrolled in a cognitive-motor stimulation study. The severity of cognitive impairment ranged from mild cognitive impairment to severe dementia. QoL was measured using the AD-related quality of life (ADRQL) scale. Social and clinical variables (for both PAD and caregiver) as well as other variables relating to cognition, activities of daily living (ADL), behavior, mood and caregiver burden were recorded. Spearman correlation coefficients and multivariate linear regression analysis were used to analyze the correlates of ADRQL (global score and subscores). Behavior and basic ADL were the best predictors of global QoL (coefficient of determination R(2)=0.57, p<0.0005). Cognition contributed marginally to global QoL (R(2)=0.03, p<0.05). The following variables were specifically associated with ADRQL subscores: household income (lower response to surroundings, R(2)=0.11), instrumental ADL (less awareness of self, R(2)=0.09), mood (better feelings and mood, R(2)=0.04), caregiver caring for another dependent person (higher social interaction, R(2)=0.04), and caregiver burden (worse feelings and mood, R(2)=0.03). In conclusion, the main determinants of QoL in PAD are functional capacities and behavior. Other medical, psychological and social variables could also be contributing to specific aspects of QoL on an individual basis. PMID- 20573410 TI - Evaluation of the learning outcomes of a year-long postgraduate training course in community geriatrics for primary care doctors. AB - There are increasing expectations on primary care doctors to shoulder a bigger share of care for patients with common geriatric problems in the community. This study aims to examine the outcomes of a postgraduate training course in geriatrics for primary care doctors. A questionnaire developed by the research team was sent to the course graduates (years 2001-2007). Ninety-eight replies were received with a response rate of 52.4% (98/187). Difference in the ratings by the respondents before and after taking the course was analyzed using the nonparametric Wilcoxon signed rank test. Most respondents felt more rewarding and had participated more in geriatric care, and the majority had improvement in their communication skills with elderly patients after taking the course. Moreover, the graduates are more confident in diagnosing and managing common geriatric problems, and deciding to which specialty to refer the elderly patients. Of the referrals, there was a significant increase to private geriatricians and a significant reduction to other specialists. The average number of elderly patients seen per day had also increased. However, little change was observed about making nursing home visits, the frequency of which remained low. Many graduates expressed difficulties in conducting nursing home visits. PMID- 20573411 TI - Pathophysiology of coronary blood flow in congenital heart disease. AB - OBJECTIVES: The aim was to investigate the effects of volume and pressure overload and increased coronary perfusion pressure on coronary flow (CF) in congenital heart disease (CHD) patients. BACKGROUND: The effects of CHD on CF are poorly mapped. METHODS: A total of 65 patients with acyanotic CHD and 49 age matched healthy controls were examined by transthoracic Doppler echocardiography. Posterior descending artery flow was measured in patients with pulmonary valve stenosis (PS) and atrial septal defects (ASDs) i.e. in lesions with right ventricular pressure or volume overload, and left anterior descending artery flow in patients with coarctation of the aorta (CoA) and ventricular septal defect (VSD), in lesions with left ventricular pressure or volume overload. The CF data in each patient group were expressed as the percent of the median for healthy controls from the same age group. RESULTS: The CF values were in VSD 172%, ASD 185%, PS 233%, and CoA 773% patients. In CoA patients body surface area (r=0.90, p<0.0001), systolic blood pressure (r=0.72, p<0.0001), diastolic blood pressure (r=0.77, p<0.0001), systolic wall tension (r=-0.77, p=0.004), and signs of inflammation (log CRP, r=-0.75, p=0.007) correlated with CF. CONCLUSIONS: The increase in CF and velocity was most significant in patients with CoA. In newborns, increased coronary perfusion pressure seems to be the most important factor for increased CF, even if the pressure is not assumed to cause a significant increase in flow over the auto-regulatory range of 70-130mmHg. We also showed that inflammation decreases CF. PMID- 20573412 TI - Association of dry cow therapy with the antimicrobial susceptibility of fecal coliform bacteria in dairy cows. AB - The prophylactic use of intramammary antimicrobial drugs at the end of lactation in dairy cows, known as dry cow therapy (DCT), is widely practiced in US dairy herds. This extremely common use of high-dose, slow-release antimicrobials may influence the ecology of bacterial flora on dairy farms. We investigated the association between the antimicrobial used for intramammary DCT and the relative number of fecal coliform bacteria with reduced susceptibility to three antimicrobial drugs in dairy cattle. Most probable number (MPN) data were estimated from 463 individual fecal samples collected from lactating cows in 15 dairy herds in Ohio, USA. These data were used to calculate the relative number of fecal coliform bacteria with reduced susceptibility to cephalothin, streptomycin, and tetracycline for individual cow samples. The farms included in this project were classified based on DCT, with 8 farms using a cephalosporin based product and the remaining 7 using a penicillin/streptomycin therapy. Results of a linear mixed model indicate that herds using a cephalosporin DCT had higher (P<0.01) relative numbers of fecal coliform bacteria with reduced susceptibility to cephalothin and streptomycin compared to those using a penicillin/streptomycin intramammary therapy. Relative numbers of fecal coliform bacteria with reduced susceptibility to tetracycline was not associated with DCT. These results suggest that high-dose slow-release antimicrobials applied locally in the udder to populations of dairy cows might influence the antimicrobial susceptibility of the enteric flora. However, the potential animal and public health implications of this result are not clear. PMID- 20573413 TI - Imperfect information in a quality-competitive hospital market. AB - We examine the implications of policies to improve information about the qualities of profit-seeking duopoly hospitals which face the same regulated price and compete on quality. We show that if hospital costs of quality are similar then better information increases the quality of both hospitals. However, if the costs are sufficiently different improved information will reduce the quality of both hospitals. Moreover, even when quality increases, better information may increase or decrease patient welfare depending on whether an ex post or ex ante view of welfare is taken. PMID- 20573414 TI - Intracellular pH of Mycobacterium avium subsp. paratuberculosis following exposure to antimicrobial compounds monitored at the single cell level. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne's disease; moreover, it seems to be implicated in the development of Crohn's disease in humans. In the present study, fluorescence ratio imaging microscopy (FRIM) was used to assess changes in intracellular pH (pH(i)) of one strain of MAP after exposure to nisin and neutralized cell-free supernatants (NCSs) from five bacteriocin-producing lactic acid bacteria (LAB) with known probiotic properties. The evaluation of pH(i) by FRIM provides information about the physiological state of bacterial cells, bypassing the long and problematic incubations needed for methods relying upon growth of MAP such as determination of colony forming units. The FRIM results showed that both nisin and the cell free supernatant from Lactobacillus plantarum PCA 236 affected the pH(i) of MAP within a few hours. However, monitoring the population for 24h revealed the presence of a subpopulation of cells probably resistant to the antimicrobial compounds tested. Use of nisin and bacteriocin-producing LAB strains could lead to new intervention strategies for the control of MAP based on in vivo application of probiotic cultures as feed additives at farm level. PMID- 20573415 TI - Modelling the influence of palmitic, palmitoleic, stearic and oleic acids on apparent heat resistance of spores of Bacillus cereus NTCC 11145 and Clostridium sporogenes Pasteur 79.3. AB - Heat resistance of spores is affected by many factors such as temperature, pH, water activity (aw) and others. Previous studies have reported that free fatty acids can affect the germination and growth of bacterial spores. In this study, we investigated the influence of free fatty acids in heating medium or in recovery medium on the heat resistance of spores of Bacillus cereus NTCC 11145 and Clostridium sporogenes Pasteur 79.3. Four free fatty acids were studied: palmitic, palmitoleic, stearic and oleic acids. During thermal treatments, the impact of these FFA in heating media was generally low, but the presence of free fatty acids in the recovery medium highly decreases bacterial spore apparent heat resistance, particularly with unsaturated fatty acids. A mathematical model was developed to describe and quantify the influence of free fatty acids in recovery media on the D-values. The z'(FFA) parameter values which quantify the impact of free fatty acids were determined. The variation of this parameter value according to the free fatty acid type was compared with MIC value variation given in the literature. The model enables the decrease in D-values in the presence of free fatty acids to be estimated. The high concentrations of free fatty acids in liver or canned duck may explain the microbial stability with low sterilization values applied. PMID- 20573416 TI - Detection of Staphylococcus aureus enterotoxins in sheep cheese and dairy desserts by multiplex PCR technique. AB - The aim of this study was to investigate the presence of Staphylococcus aureus (S. aureus) and staphylococcal enterotoxins (SEs) genes in sheep cheese and dairy dessert samples by multiplex PCR (mPCR) technique. A total of 150 samples were analyzed consisting of 50 dairy dessert samples and 100 sheep cheese. Coagulase positive staphylococci (CPS) were found in 86 (57.3%) out of 150 analyzed samples. S. aureus were isolated from 60 (60%), 26 (52%) of sheep cheese and from of dairy desserts, respectively. Five suspected colonies were tested from each sheep cheese and dairy dessert samples for phenotypic and genotypic characterizations. A total of 430 isolates from the 86 positive samples were investigated in this study. Eighty (18.6%) isolates were characterized as S. aureus. The enterotoxin genes (sea, seb, sec, sed) were found in 13 (3.02%) out of 80 isolates. From cheese isolates, sea, seb and sed were detected in 5 (1.6%), 2 (0.6%), 1 (0.3%), respectively. From dairy dessert isolates, sea, sec and sed were detected in 3 (2.3%), 1 (0.76%), 1 (0.76%), respectively. The presence of SEs was identified in 12 (2.8%) out of 80 isolates by using ELISA technique. It was determined that these SEs had a distribution of 7 (1.6%) SEA, 2 (0.46%) SEB, 1 (0.23%) SEC, and 2 (0.46%) SED. SEs were found in 7 (2.3%) cheese and 5 (3.8%) dairy dessert isolates. In conclusion, S.aureus and their SEs were found to be present in sheep cheese and dairy desserts in this study. It is emphasized that the presence of S. aureus and their SEs genes in sheep cheese and dairy desserts may be regarded as a potential risk for human health. PMID- 20573417 TI - Development and evaluation of multilocus variable number tandem repeat analysis for fine typing and phylogenetic analysis of Salmonella enterica serovar Typhimurium. AB - We identified 16 variable number tandem repeat (VNTR) loci for Salmonella enterica serovar Typhimurium. These VNTRs were evaluated with panels of 183 diverse isolates, 203 closely related isolates and 54 isolates from seven outbreaks. The evaluations revealed that five of the 16 VNTRs had diversity values greater than 0.5, and three (STTR5, STTR6 and STTR10) were hypervariable. The results obtained from the outbreak isolates suggested that the 16 VNTRs were considerably stable in isolates recovered during a normal outbreak time course. Multilocus VNTR analysis (MLVA) based on four most variable VNTRs (MLVA4), exhibited a better resolving power over pulsed-field gel electrophoresis (PFGE) in discriminating among isolates, in particular among the closely-related isolates. An MLVA5, which is based on five VNTRs and has been widely used in many European laboratories, displayed a level of discrimination close to MLVA4. The phylogenetic tree established using the MLVA16 profiles presented four distinct clusters, which were associated with four different phage types. Therefore, MLVA based on four or five highly variable VNTRs is sufficiently powerful to supplement or replace PFGE for outbreak investigation and surveillance of S. Typhimurium infections, and MLVA data based on 16 VNTRs can be useful in establishing clonal structures among isolates. PMID- 20573418 TI - Microglia in the healthy and degenerating retina: insights from novel mouse models. AB - In contrast to the tremendous amount of research data from the central nervous system, relatively little is known about microglial homeostasis in the retina. This may be explained by a strong research bias towards important brain pathologies including Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. In addition, there are specific technical limitations which hampered the analysis of retinal microglia, including their relatively small number in ocular tissue. The lack of experimental tools also prevented direct visualization and molecular analysis of this specialized neuronal macrophage population. Over the last few years, this situation has changed considerably as more and more retinal disorders have come into focus. Many rare monogenic forms as well as more prevalent complex disorders, in particular the age-related macular degeneration involves innate immune mechanisms. As a consequence, new genetic and experimental mouse models have been developed that mimic various forms of human retinal degeneration. In conjunction with these disease models, novel macrophage/microglia-specific reporter mice were established that allow the monitoring of retinal microglia in situ and in vivo. This review summarizes recent findings from these mouse models and thereby provides an overview of microglial homeostasis in the healthy and degenerating retina. Based on this knowledge, microglia-targeted therapies are envisioned which could delay or attenuate degenerative retinal disease. PMID- 20573419 TI - Trichostatin A blocks type I interferon production by activated plasmacytoid dendritic cells. AB - Plasmacytoid dendritic cells (PDC) represent the main type I interferon (IFN-I) producing cells. Emerging evidence supports a role for IFN-I in autoimmune diseases. Given the central role of PDC in the pathogenesis of systemic lupus erythematosus (SLE), we investigated the effect of Trichostatin A (TSA), a prototypic histone deacetylase inhibitor, on PDC activation. TSA inhibited the production of IFN-I, TRAIL and of the pro-inflammatory cytokines TNFalpha and IL 6 by CpG-activated PDC. These effects were associated with the inhibition of IFN Regulatory Factor (IRF)-7 nuclear translocation. Furthermore, TSA was also effective in inhibiting the production of IFNalpha by PDC cultured in vitro in the presence of serum obtained from SLE patients. This study describes a new level of regulation of immune responses by histone deacetylase inhibitors and defines the molecular basis for new strategies to be exploited in the treatment of autoimmune diseases. PMID- 20573420 TI - Plk1-mediated mitotic phosphorylation of PinX1 regulates its stability. AB - PinX1 was originally identified as a Pin2/TRF1-interacting protein that suppresses telomerase activity via its telomerase inhibitor domain (TID) and regulates the nucleolar localization of TRF1 in telomerase-positive cells. In addition to its telomeric localization, PinX1 can be found in the nucleoli of human cells. Our recent studies have shown that PinX1 localizes to the chromosome periphery and kinetochores in mitosis. Depletion of PinX1 results in lagging chromosomes in mitosis and micronuclei in interphase. However, less is known about the post-translational modification of PinX1 in mitosis. Here, we show that Polo-like kinase 1 (Plk1) is a novel interacting protein of PinX1. Plk1 interacts with and phosphorylates PinX1 in vivo and in vitro. Overexpression of Plk1 promotes protein turnover of PinX1, a process that depends on ubiquitin associated proteasomal degradation. Depletion of Plk1 using siRNA increases the stability of PinX1 at protein level in mitosis. Moreover, Plk1-mediated phosphorylation of PinX1 at five phosphorylation sites is essential for its Plk1 induced degradation. These findings suggest that Plk1 may negatively regulate the stability of PinX1 by mitotic phosphorylation. PMID- 20573421 TI - Podosome regulation by Rho GTPases in myeloid cells. AB - Myeloid cells form a first line of defense against infections. They migrate from the circulation to the infected tissues by adhering to and subsequently crossing the vascular wall. This process requires precise control and proper regulation of these interactions with the environment is therefore crucial. Podosomes are the most prominent adhesion structures in myeloid cells. Podosomes control both the adhesive and migratory properties of myeloid cells and the regulation of podosomes is key to the proper functioning of these cells. Here we discuss the regulation of podosomes by Rho GTPases, well known regulators of adhesion and migration, focusing on myeloid cells. In addition, the regulation of podosomes by GTPase regulators such as GEFs and GAPs, as well as the effects of some Rho GTPase effector pathways, will be discussed. PMID- 20573422 TI - [What are the pharmacological costs of a well-controlled diabetic?]. AB - OBJECTIVE: To evaluate the cost of glucose lowering treatment (GLT) in our diabetic patients (DP). DESIGN: Cross-sectional descriptive study. SETTING: Urban primary health care centre. PARTICIPANTS: Random sample of 294 DP with HPT. MEASUREMENTS: Principal variable: annual cost of GLT. Secondary Variables: age, sex, type of diabetes (DM), prescribing doctor, level of control, number of glucose lowering drugs, cardiovascular risk factors and complications. RESULTS: A total of 294 diabetic patients were included, with a mean age 71.7+/-13.3 years; 52.7% women; 93.2% DM2; Annual cost of GLT: 82.979 ?,(281.9 ?/patient/year). General practitioner (GP) originated 32.3% of the treatments (17.7% of the costs). Annual average expenditure was significantly higher in DM1 patients, patients on treatment with triple therapy and patients controlled by an endocrinologist in a reference hospital. In the multiple linear regression the variables that explained the variation in the cost were the type of Diabetes mellitus (P<0.0001), prescription by hospital endocrinologist (p=0,002), number of glucose lowering drugs(P<0.0001), diabetic retinopathy(P: 0.019) and chronic renal failure (P: 0.027). These variables explained 44.5% of the annual cost variation of the GLT (R(2):0.445). CONCLUSIONS: There is a wide variation in the costs arising from GLT of our diabetic patients. We conclude, it is essential to improve coordination between levels of care, encourage the design and use of clinical guidelines to achieve more efficient control of our patients. PMID- 20573423 TI - N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hydrazides: synthesis and anticonvulsant activity. AB - A series of N'-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4 substituted hydrazides were synthesized using appropriate synthetic route and characterized by elemental analysis and spectral data. The anticonvulsant activity of some of the synthesized compounds were evaluated against maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) induced seizure models in mice. The neurotoxicity were assessed using the rotorod method. All the test compounds were administered at doses of 30, 100, and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. Among the compound tested, all except 5 g showed protection from seizures in both the animal models. Some titled compounds exhibited lesser CNS depression and neurotoxicity compared to phenytoin. PMID- 20573424 TI - Design & synthesis of 2-(substituted aryloxy)-5-(substituted benzylidene)-3 phenyl-2,5-dihydro-1H-[1,2,4] triazin-6-one as potential anticonvulsant agents. AB - A series of 2-(substituted aryloxy)-5-(substituted benzylidene)-3-phenyl-2,5 dihydro-1H-[1,2,4] triazin-6-one were designed & synthesized using appropriate synthetic route keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and CNS activities. After intraperitoneal injection to mice, some synthesized derivatives were examined in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ) induced seizure and neurotoxicity screens. Those found potent were also evaluated for behavioural impairment and depression activity. Among the compound tested, 5 eIX showed protection from seizures in both the animal models at dose level of 30 mg/kg while 5 bII &5 cII showed protection against scPTZ model at same dose level. Some titled compounds exhibited lesser CNS depression and neurotoxicity compared to clinically effective drug. PMID- 20573426 TI - Synthesis and preliminary bioactivity assays of 3,4-dichloro-5-(omega hydroxyalkylamino)-2(5H)-furanones. AB - 5-(Omega-hydroxyalkylamino) derivatives of mucochloric acids were synthesized through a facile substitution reaction of 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid) acetate or 5-methylcarbonate with an appropriate amino alcohol or aminodiol. The obtained products were characterized and screened for their antibacterial and antiprotozoal activities. PMID- 20573425 TI - Design, synthesis and anti-ulcerogenic effect of some of furo-salicylic acid derivatives on acetic acid-induced ulcerative colitis. AB - Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present work describes design and synthesis of 3 aminofurosalicylic acid 4, azo-conjugates with aniline 2a, 4-ASA 2b or sulphapyridine 2c as well as N-arylsulphonamido 5, chlorosulphonyl 6, aminosulphonyl 7 and N-arylaminosulphonyl derivatives 8 (positional isosters of 5). All the synthesized compounds were evaluated for their anti-ulcerogenic effect on acetic acid-induced ulcerative colitis in rats. It was noticed that oral treatment with sulphasalazine (a reference drug) and the tested compounds 2a, 2c, 4 and 5c in equimolar doses significantly reduced the intensity of lesion score, ulcer area, ulcer index and wet weight/length ratio compared to the control group. On the other hand, compounds 2b, 5a, 5b and 7 had a lower anti ulcerogenic efficacy. Also, the antimicrobial activity of the synthesized compounds was screened in vitro using the agar diffusion assay technique. In addition, docking of the tested compounds into cycloxygenase II using molecular operating environment (MOE) was performed in order to rationalize the obtained biological results and their mechanism of action. PMID- 20573428 TI - The effectiveness of high fidelity simulation on medical-surgical registered nurses' ability to recognise and respond to clinical emergencies. AB - BACKGROUND: There is a paucity of evidence regarding the efficacy in preparing medical-surgical nurses to respond to patients with acutely deteriorating conditions. STUDY AIM: The aim of this study was to evaluate registered nurses' ability to respond to the deteriorating patient in clinical practise following training using immersive simulation and use of a high fidelity simulator. METHODS: This study was a follow-up survey of medical-surgical graduate nurses following immersive high fidelity simulation training. Thirty eight registered nurses practising in medical-surgical areas completed the simulation as part of university graduate study. A follow-up survey of the graduate medical-surgical registered nurses conducted three months following completion of a high fidelity simulation-based learning experience. Outcomes consisted of the number of times skills were used in practise and the usefulness of simulation in preparing for actual emergency events. RESULTS: Participants reported a total of 164 clinical patient emergencies in the follow-up time period including: 46% cardiac, 32% respiratory, 10% neurological, 7% cardiac arrest and 5% related to electrolyte disturbances. The ability to respond in a systematic way, handover to the emergency team and airway management were identified as the skills most improved during patient emergencies following simulation. The most useful aspects of the simulation experience identified were scenario debriefing and assertiveness training. Participants with less years of clinical experience were more likely to report practising the team leader role and debriefing as the most useful aspects of simulation. CONCLUSIONS: The skills practised in simulation were highly relevant to participants practise in medical-surgical areas. Non-technical skills, including assertiveness skills should be considered in future emergency training courses for nurses. PMID- 20573427 TI - Best Practice Guidelines for use of OSCEs: Maximising value for student learning. AB - Objective structured clinical examinations (OSCEs) are a regular component of Bachelor of Nursing (BN) programs within Australia and internationally. OSCEs are a valuable strategy to assess 'fitness to practice' at the students' expected level of clinical practice within a nursing context where the importance of accurate patient assessment is paramount. This report discusses the integration of seven proposed 'Best Practice Guidelines' (BPG) into an undergraduate BN program in Queensland, Australia. A range of learning and assessment strategies was introduced in accordance with the adoption of these guidelines to maximise student engagement. There is some evidence that these strategies have directly assisted in enhanced student confidence around clinical practice and provide preliminary evidence of the effectiveness of BPG for OSCEs within nursing programs internationally. PMID- 20573429 TI - Movement of a tritium plume in shallow groundwater at a legacy low-level radioactive waste disposal site in eastern Australia. AB - Between 1960 and 1968 low-level radioactive waste was buried in a series of shallow trenches near the Lucas Heights facility, south of Sydney, Australia. Groundwater monitoring carried out since the mid 1970s indicates that with the exception of tritium, no radioactivity above typical background levels has been detected outside the immediate vicinity of the trenches. The maximum tritium level detected in ground water was 390 kBq/L and the median value was 5400 Bq/L, decay corrected to the time of disposal. Since 1968, a plume of tritiated water has migrated from the disposal trenches and extends at least 100 m from the source area. Tritium in rainfall is negligible, however leachate from an adjacent and fill represents a significant additional tritium source. Study data indicate variation in concentration levels and plume distribution in response to wet and dry climatic periods and have been used to determine pathways for tritium migration through the subsurface. PMID- 20573430 TI - Metabolic cost and mechanical work during walking after tibiotalar arthrodesis and the influence of footwear. AB - BACKGROUND: This study examined metabolic energy cost and external mechanical work for step-to-step transitions after tibiotalar arthrodesis, and the effect of MBT rocker bottom shoes. METHODS: Oxygen uptake, forceplate and kinematic data were recorded in 18 controls and 15 patients while walking at a fixed speed of 1.25 m/s in three walking conditions: barefoot, normal walking shoes and MBT rocker bottom shoes. Metabolic energy cost, external mechanical work, and the roll-over shape of the ankle-foot complex were analyzed. FINDINGS: Tibiotalar arthrodesis leads to higher metabolic energy cost during walking. During step-to step transitions positive work during push-off with the impaired ankle was decreased but negative work during collision was not affected. The roll-over shape of the ankle-foot complex did not differ between groups and shoe conditions. However, both in patients and controls rocker bottom shoes did lead to decreased positive work at push-off and increased negative work at collision and consequently higher metabolic energy cost of walking. INTERPRETATION: External mechanical work for step-to-step transitions is not different between patients and controls and could not account for the higher metabolic energy cost in patients. Apparently, patients adopt a different walking strategy that limits step-to-step transition cost but nevertheless induces a higher metabolic energy cost. Despite restricted ankle movement, patients retain a normal roll-over shape of the ankle-foot complex. MBT shoes do not affect roll-over shape and appear to have a counterproductive effect on step-to-step transition cost and walking economy. PMID- 20573432 TI - Politics, public health and pessimism: should we take studies on welfare states and public health further? A commentary on Tapia Granados. PMID- 20573431 TI - Brominated flame retardants and perfluorinated chemicals, two groups of persistent contaminants in Belgian human blood and milk. AB - We assessed the exposure of the Flemish population to brominated flame retardants (BFRs) and perfluorinated compounds (PFCs) by analysis of pooled cord blood, adolescent and adult serum, and human milk. Levels of polybrominated diphenyl ethers (PBDEs) in blood (range 1.6-6.5 ng/g lipid weight, lw) and milk (range 2.0 6.4 ng/g lw) agreed with European data. Hexabromocyclododecane ranged between <2.1-5.7 ng/g lw in milk. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) dominated in blood and ranged between 1 and 171 ng/mL and <0.9-9.5 ng/mL, respectively. Total PFC levels in milk ranged between <0.5-29 ng/mL. A significant increase in PBDE concentrations was detected from newborns (median 2.1) to the adolescents and adults (medians 3.8 and 4.6 ng/g lw, respectively). An identical trend was observed for PFOS, but not for PFOA. We estimated that newborn exposure to BFRs and PFCs occurs predominantly post natally, whereas placental transfer has a minor impact on the body burden. PMID- 20573433 TI - Seasonality in suicide--a review and search of new concepts for explaining the heterogeneous phenomena. AB - Seasonality is one of the oldest and most resistant-to-elucidation issues in suicide research. However, in recent years epidemiological research has yielded new results, which provide new perspectives on the matter. This qualitative review summarizes research published since the 1990 s. In particular, the focus is on studies dealing with the historical change of seasonality, cross-sectional comparisons including method-specific diversity, and the association with weather variables and other putative covariates. Recent research has shown that in Western countries the seasonality of suicide is tending to diminish and may, eventually, disappear. It can no longer be considered a universal and homogeneous phenomenon. In addition, different major seasonal cycles have now been determined which mainly depend on different suicide methods. Just as in the epidemiology of suicide methods, the (seasonal) availability and perceived adequacy of methods emerge as the major driving force beyond the seasonal phenomena in suicide. PMID- 20573434 TI - Masculinity, moralities and being cared for: an exploration of experiences of living and dying in a hospice. AB - Hospices are playing an increasingly important role in end of life care in Australia and internationally and the in-patient hospice experience has not been well documented by social scientists. This paper explores some important facets of the contemporary hospice experience through an examination of the perspectives of 11 male and 9 female Australian in-patients in the last few weeks of their lives. Through a series of qualitative in-depth interviews, we explore their conceptions of death and dying and their experiences of being cared for. The results illustrate a range of important themes including: tensions around what constitutes 'the good death'; dying and caring as moral practice; and, the centrality of gender identity and relations in shaping experiences of dying and caring. We argue for a sociological approach to death and dying that better elucidates the interplay of identity, morality and relationality at the end of life. PMID- 20573435 TI - Mapping self-reports of working memory deficits to executive dysfunction in Fragile X Mental Retardation 1 (FMR1) gene premutation carriers asymptomatic for FXTAS. AB - Fragile X Syndrome is a neurodevelopmental disorder that is caused by the silencing of a single gene on the X chromosome, the Fragile X Mental Retardation 1 (FMR1) gene. In recent years, the premutation ("carrier") status has received considerable attention and there is now an emerging consensus that despite intellectual functioning being within the average range premutation males present with subtle executive function impairments that include poor inhibitory control, working memory deficits, and poor planning skills. The ranges of these skills, although not nearly as severe as seen in the full mutation, nonetheless serve to differentiate males with the premutation from males in the unaffected population. In the present study we extend these findings to suggest that behavioral markers, specifically self-report on the Brown Attention-Deficit Disorder Rating Scales, may serve as a clinically useful indicator or "signature" of the Fragile X Premutation status. We discuss the possibility that this measure provides a means to identify those at greatest risk for developing the newly identified neurodegenerative disorder that affects some premutation males - Fragile X Tremor/Ataxia Syndrome (FXTAS). PMID- 20573436 TI - [Hibernoma of the thigh]. AB - Hibernoma is a rare benign tumour of brown fat. It presents as a voluminous slow growing mass in the regions where remnants of brown fat can remain in adults. We report a case of a hibernoma on the thigh and present the diagnostic and therapeutic elements of this type of tumour, whose differential diagnosis of liposarcoma. PMID- 20573437 TI - [Time trends of Th1 and th2 cytokines in induced sputum of asthmatic subjects during acute upper respiratory viral infections]. AB - FUNDAMENTALS: Many asthma exacerbations are caused by respiratory viral infections that induce the interplay between Th1 and Th2 immune responses. However, the time trends for Th1 and Th2 immune responses during these phenomena have not been well studied. OBJECTIVE: To identify possible mechanisms underlying the link between respiratory viral infections and asthma exacerbations. PATIENTS AND METHODS: We recruited 40 adults aged 21-58 years for 4 groups. A. Healthy, B. Healthy with viral infection, C. Mild to moderate asthma and D. Same as C, but with viral infection. Th1 and Th2 cytokines in induced sputum samples during the course of acute upper respiratory viral infections in otherwise healthy and asthmatic subjects were monitored. IL-4, IL-5 and IFN-gamma were assayed by ELISA. Viral infection symptoms and asthma severity scores were monitored. Time trends were analyzed using linear mixed models. RESULTS: IL-4 and IL-5 levels in groups C and D were higher than in groups A and B. IFN-gamma levels and viral infection symptoms scores in group B spiked by day 2 and rapidly declined by day 7, while in group D, IFN-gamma and symptoms scores for viral infection and asthma peaked much later (days 3-5) and slowly declined. The ratios of IL-4 and IL-5 to IFN-gamma in group D were significantly higher than in group C. CONCLUSIONS: Infection-induced asthma exacerbations may be due to impaired anti-viral Th1 immune responses. There appears to be a critical window of 3-5 days for therapeutic intervention. PMID- 20573438 TI - Fresh-frozen plasma transfusion strategy in trauma with massive and ongoing bleeding. Common (sense) and sensibility. AB - During trauma resuscitation involving massive transfusion, the best fresh-frozen plasma to packed red blood cells ratio is unknown. No randomised controlled trial (RCT) is available on this subject, although there are plenty of observational studies suggesting that the ratio should be about 1:1. This ratio also makes more physiological sense, and we suggest that in patients with massive and ongoing bleeding, it is a sensible strategy with which to start resuscitation. PMID- 20573440 TI - Non-typeable Haemophilus influenzae and tubo-ovarian abscesses: case report and brief review. PMID- 20573441 TI - Free-energy landscape of glycerol permeation through aquaglyceroporin GlpF determined from steered molecular dynamics simulations. AB - The free-energy landscape of glycerol permeation through the aquaglyceroporin GlpF has been estimated in the literature by the nonequilibrium method of steered molecular dynamics (SMD) simulations and by the equilibrium method of adaptive biasing force (ABF) simulations. However, the ABF results qualitatively disagree with the SMD results that were based on the Jarzynski equality (JE) relating the equilibrium free-energy difference to the nonequilibrium work of the irreversible pulling experiments. In this paper, I present a new SMD study of the glycerol permeation through GlpF to explore the free-energy profile of glycerol along the permeation channel. Instead of the JE in terms of thermodynamic work, I use the fluctuation-dissipation theorem (FDT) of Brownian dynamics (BD), in terms of mechanical work, for extracting the free-energy difference from the nonequilibrium work of irreversible pulling experiments. The results of this new SMD-BD-FDT study are in agreement with the experimental data and with the ABF results. PMID- 20573442 TI - Sorption isotherm studies of Cd(II) ions using living cells of the marine microalga Tetraselmis suecica (Kylin) Butch. AB - The present work reports the use of living cells of the marine microalga Tetraselmis suecica for the biosorption of cadmium ions. For a better understanding of the biosorption characteristics, three fractions of removed cadmium (total, bioadsorbed and intracellular) were measured in the cells after 24 and 72 h of exposure to different initial cadmium concentrations (0.6-45 mg L( 1)). Both the Langmuir and Freundlich models were suitable for describing the sorption of cadmium ions by this microalga. The maximum sorption capacity was estimated to be 40.22 mg Cd g(-1) after 72 h using the Langmuir sorption model. In the lower cadmium concentrations, metal removed intracellularly was higher than that removed on the microalgal cell surface. Therefore, the intracellular fraction contributed more to the total removed cadmium than the fraction bioadsorbed to the cellular surface. The results showed that the cadmium removal capacity using living biomass could be much more effective than with non-living biomass due to the intracellular bioaccumulation. According to the microorganism selected and its tolerance to the toxic effect of the metal, the cadmium content in the intracellular fraction can become very significant, just like it happened with Tetraselmis. PMID- 20573443 TI - Dynamic progression of overactive bladder and urinary incontinence symptoms: a systematic review. AB - CONTEXT: Overactive bladder (OAB) and urinary incontinence (UI) are worldwide public health problems. Longitudinal epidemiologic studies that assess the natural history of OAB and UI are valuable in making accurate prognoses, determining causes and consequences, and predicting resource utilization. OBJECTIVE: Our aim was to assess whether the severity of OAB and UI symptoms progress dynamically over time, with the secondary aim of assessing factors that may be associated with symptom progression and regression. EVIDENCE ACQUISITION: A systematic review of English articles published between January 1, 1990, and September 20, 2009, was conducted using PubMed and Embase. Search terms included longitudinal, natural history, overactive bladder, incontinence, progression, remission, and regression. Eligibility was assessed by Dr. Irwin with editorial assistance. Studies were required to be longitudinal and population based; meeting abstracts and conference proceedings were excluded. Results were assessed qualitatively. EVIDENCE SYNTHESIS: Overall, the 7 longitudinal studies of OAB and 14 longitudinal studies of UI reviewed reported an increase in the incidence and remission/regression of both OAB and UI symptoms over time that varied across studies (eg, OAB incidence, 3.7-8.8%; UI incidence, 0.8-19%). The studies provide evidence for a dynamic progression of OAB and UI symptoms (eg, among women with OAB without urge urinary incontinence [UUI], 28% reported OAB with UUI 16 yr later) and also show that although symptom severity progresses dynamically, for many individuals symptoms also persist over long time periods. CONCLUSIONS: The results support the hypothesis that OAB and UI symptom severity progress dynamically and are also sustained over time. However, the variations in symptom definitions and methods used across studies prevent statistical determinations of overall incidence rates. The recognition of OAB and UI as progressive conditions allows for a shift from the current treatment paradigm of symptom control alone to one of symptom management. PMID- 20573444 TI - Hypoxia and retinoic acid-inducible NDRG1 expression is responsible for doxorubicin and retinoic acid resistance in hepatocellular carcinoma cells. AB - Hypoxia may activate survival signals in cancer cells. Moreover, hypoxic cells are less sensitive than normoxic cells to doxorubicin cytotoxicity, a potent activator of the p53 tumor suppressor gene. N-myc downstream-regulated gene-1 (NDRG1) is a hypoxia- and retinoic acid-inducible protein, and has been previously implicated in carcinogenesis. As this protein is also a downstream target of p53 and hepatocellular carcinoma (HCC) cells frequently evidence resistance to retinoic acid (RA) cytotoxicity, we attempted to determine whether the suppression of NDRG1 expression may sensitize HCC cells to doxorubicin and/or RA cytotoxicity. HCC cells expressed NDRG1 protein, and the expression of this protein was hypoxia- and RA-inducible. Doxorubicin treatment induced HCC cell cytotoxicity via the activation of mitochondrial apoptotic signals, including caspase-9 activation. Hypoxic HCC cells are less sensitive to doxorubicin-induced apoptosis. The suppression of NDRG1 expression either by siRNA or flavopiridol sensitized hypoxic HCC cells to doxorubicin cytotoxicity, and this was attributed to more profound augmentation of JNK and caspase-9 activation. The suppression of NDRG1 expression also sensitized RA-resistant HCC cells to RA-induced apoptosis, and this sensitization was more apparent in hypoxic HCC cells than in normoxic cells. Glutaredoxin2 expression was down-regulated in NDRG1-suppressed HCC cells. These results show that hypoxia- and RA-inducible NDRG1 expression is responsible for doxorubicin and RA resistance in HCC cells. Thus, the selective interruption of NDRG1 signaling may prove to be therapeutically useful in HCCs, particularly in the advanced infiltrative type of tumors exposed to hypoxic environments. PMID- 20573445 TI - Agro-industrial waste 'wheat bran' for the biosorptive remediation of selenium through continuous up-flow fixed-bed column. AB - Present study deals with the utilization of an agro-industrial waste wheat bran for the remediation of selenium species, Se(IV) and Se(VI) by continuous up-flow fixed-bed column system. Laboratory-scale column tests were performed to determine potentiality of wheat bran at various bed height, flow rates and initial metal ion concentration and it was found to be very potential biosorbent as it showed good sorption capacities of 72.54 microg/g and 62.51 microg/g for Se(IV) and Se(VI) respectively. Different models like Bed Depth Service Time (BDST), Thomas and Yoon-Nelson were applied to the experimental sorption data. The data showed very good fit to BDST model and sorption capacities (N(o)) computed using BDST model were 26,664 microg/L and 26,400 microg/L for Se(IV) and Se(VI) respectively. Also Yoon-Nelson model was found to show good agreement with the experimental kinetic results as compared to the Thomas model. Wheat bran was amenable to efficient regeneration with 10% NaOH. The biosorbent retained most of its original uptake capacity over three cycles of use. The excellent reusability of the biosorbent could lead to development of a viable metal remediation technology. Life factor calculation revealed that biosorbent bed will have sufficient capacity to avoid breakthrough at time t=0 up to 12.17 cycles for Se(IV) and 6.28 cycles for Se(VI) and bed would be completely exhausted after 56.89 cycles for Se(IV) and 18.73 cycles for Se(VI). PMID- 20573446 TI - Mesoporous silica functionalized with 1-furoyl thiourea urea for Hg(II) adsorption from aqueous media. AB - New organic-inorganic hybrid materials were prepared by covalently anchoring 1 furoyl thiourea on mesoporous silica (SBA-15). By means of various characterization techniques (X-ray diffraction, nitrogen adsorption-desorption, thermogravimetric analysis, and FTIR spectroscopy) it has been established that the organic groups were successfully anchored on the SBA-15 surfaces and the ordering of the inorganic support was preserved during the chemical modifications. The hybrid sorbents exhibited good ability to remove Hg(II) from aqueous solution. Thus, at pH 6, the adsorption capacity of mercury ions reached 0.61 mmol g(-1). PMID- 20573447 TI - Effective utilization of waste cathode ray tube glass--crystalline silicotitanate synthesis. AB - A novel process for crystalline silicotitanate (CST) synthesis was developed using waste cathode ray tube (CRT) panel glass as silicon source. The key trait of the process was to extract most of the silicon out of the glass for CST preparation, but leave Ba and Sr in the residue which had the potential to be employed as raw material for metallic Ba and Sr metallurgy. In the synthesis process, waste CRT panel glass was firstly treated by supercritical water (SCW) NaOH solution for Si extraction, then sol-gel and hydrothermal treatments were used for CST preparation. 80% of Si in the glass could be extracted into the solution, while Sr and Ba were enriched in the residue in the form of Sr(2)SiO(4) and Ba(2)Si(3)O(8), respectively. Sr and Ba contents in the residue were 2-3 times higher than those in the raw glass. SEM, XRD and TEM results indicated that CST was successfully synthesized. Ion exchanging experiments showed that the batch distribution coefficient of the synthesized CST to Cs(+) was up to 1.2x10(4) mL/g at pH 0.26. PMID- 20573449 TI - Fatigue in primary care: longitudinal associations with pain. AB - So far, most studies on the association between pain and fatigue have used cross sectional data. We analysed the possibilities for a temporal relationship between pain and fatigue in a cohort study of patients presenting with fatigue in primary care. Of 856 recruited patients, 642 (75%) completed postal questionnaires after the consultation, and at one, four, eight and 12 months follow-up, with completion rates ranging from 82% to 88%. Pain was measured using the Short-Form health survey (SF-36) and fatigue using the severity scale of the Checklist Individual Strength (CIS). Longitudinal associations were analysed using generalised estimated equations (GEE). We used three different models assessing possible relationships between the symptoms in time, either in the same intervals or with a time-lag, suggesting either a synchronous or temporal association. The regression coefficients were strongest in the model assessing synchronous change, indicating that a one-point improvement in pain was associated with a 0.25 improvement in fatigue in the same time interval (adjusted for potential confounding). Baseline duration of fatigue and expectations of its future course significantly modified the association in this model, with stronger associations between changes in pain and fatigue found in patients with a shorter duration of fatigue or more positive expectations. The models using a time lag showed a significant but inverse association between changes in pain and subsequent changes in fatigue. The results indicate that changes in pain and fatigue are directly related in time, rather than showing temporal associations. PMID- 20573448 TI - A multicenter, randomized, triple-masked, placebo-controlled trial of the effect of ambulatory continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on general orthopaedic wards. AB - A continuous femoral nerve block (cFNB) involves the percutaneous insertion of a catheter adjacent to the femoral nerve, followed by a local anesthetic infusion, improving analgesia following total knee arthroplasty (TKA). Portable infusion pumps allow infusion continuation following hospital discharge, raising the possibility of decreasing hospitalization duration. We therefore used a multicenter, randomized, triple-masked, placebo-controlled study design to test the primary hypothesis that a 4-day ambulatory cFNB decreases the time until each of three predefined readiness-for-discharge criteria (adequate analgesia, independence from intravenous opioids, and ambulation 30m) are met following TKA compared with an overnight inpatient-only cFNB. Preoperatively, all patients received a cFNB with perineural ropivacaine 0.2% from surgery until the following morning, at which time they were randomized to either continue perineural ropivacaine (n=39) or switch to normal saline (n=38). Patients were discharged with their cFNB and portable infusion pump as early as postoperative day 3. Patients who were given 4 days of perineural ropivacaine attained all three criteria in a median (25th-75th percentiles) of 47 (29-69)h, compared with 62 (45 79)h for those of the control group (Estimated ratio=0.80, 95% confidence interval: 0.66-1.00; p=0.028). Compared with controls, patients randomized to ropivacaine met the discharge criterion for analgesia in 20 (0-38) versus 38 (15 64)h (p=0.009), and intravenous opioid independence in 21 (0-37) versus 33 (11 50)h (p=0.061). We conclude that a 4-day ambulatory cFNB decreases the time to reach three important discharge criteria by an estimated 20% following TKA compared with an overnight cFNB, primarily by improving analgesia. PMID- 20573451 TI - Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia. AB - Chronic stressful events induce biochemical, physiological and psychological changes, resulting in stress-related neuropsychiatric disorders, such as anxiety or depression. Using repeated social defeat as a stressful event model, we show that this preclinical paradigm induces a transient increase in the expression of the genes encoding the pro-inflammatory molecules iNOS and COX-2. We provide the first demonstration that chronic stress affects spinal plasticity through a mechanism involving local neuroinflammation. The functional consequences of such neuroinflammation are associated with a transient decrease in the mechanical nociceptive threshold. Administration of the cholecystokinin(CCK)-2 receptor antagonist, CI-988, directly into the Rostral Ventromedial Medulla reverses the chronic stress-induced decrease in the nociceptive threshold. These data strongly suggest that chronic stress induces a spinal neuroinflammation associated with transient sensory hypersensitivity involving the activation of CCK-dependent nociceptive descending facilitatory pathways. Pharmacological data show that chronic social stress-induced long-lasting state of anxiety is not responsible for maintaining the spinal neuroinflammation and, therefore, for the associated sensory hypersensitivity. Conversely, an evaluation of pain-related behavior in the formalin model indicates that anxiety is directly related to prolonged hyperalgesia prevented by systemic benzodiazepine or CCK-2 receptor antagonist treatments. The present study highlights the adverse effects of chronic stress on spinal neuroinflammation triggering sensory hypersensitivity. Exploration of this phenomenon points out the divergence between pain sensitivity and anxiety-induced hyperalgesia, which is in agreement with clinical observations. Altogether, these data open up new perspectives for clinical research devoted to the evaluation and treatment of pain in anxio-depressive patients. PMID- 20573452 TI - A precession electron diffraction study of alpha, beta phases and Dauphine twin in quartz. AB - Precession electron diffraction is used to distinguish between the hexagonal beta high-temperature and the trigonal alpha low-temperature phases of SiO2 quartz. The structures just differ by a kink of the SiO4 tetrahedra arranged along spiraling chains, which induces a loss of the two-fold axis and subsequent twinning in the low-temperature phase. Conventional selected-area electron diffraction (SAED) does not enable the phases distinction since only the intensity of reflections is different. It becomes possible with precession that reduces the dynamical interactions between reflections and makes their intensity very sensitive to small variations of the electron structure factors. Distinction between the twinned individuals in the low-temperature phase is then easily made and the twin law is characterized using stereographic projections. The actual symmetry of precessed zone axis patterns is also examined in detail. Using dynamical intensity simulations, it is shown that under certain thickness conditions, the diffraction class symmetry can be observed on selected area patterns that are to be used in the case of beam sensitive materials such as quartz. PMID- 20573450 TI - Inhibition of microglial P2X4 receptors attenuates morphine tolerance, Iba1, GFAP and mu opioid receptor protein expression while enhancing perivascular microglial ED2. AB - Anti-nociceptive tolerance to opioids is a well-described phenomenon, which severely limits the clinical efficacy of opioids for the treatment of chronic pain syndromes. The mechanisms that drive anti-nociceptive tolerance, however, are less well understood. We have previously shown that glia have a central role in the development of morphine tolerance and that administration of a glial modulating agent attenuated tolerance formation. Recently, we have demonstrated that morphine enhances microglial Iba1 expression and P2X4 receptor-mediated microglial migration via direct mu opioid receptor signaling in in vitro microglial cultures. We hypothesize that P2X4 receptors drive morphine tolerance and modulate morphine-induced spinal glial reactivity. Additionally, we hypothesize that perivascular microglia play a role in morphine tolerance and that P2X4 receptor expression regulates perivascular microglia ED2 expression. To test these hypotheses, rats were implanted with osmotic minipumps releasing morphine or saline subcutaneously for seven days. Beginning three days prior to morphine treatment, P2X4 receptor antisense oligonucleotide (asODN) was injected intrathecally daily, to selectively inhibit P2X4 receptor expression. P2X4 receptor asODN treatment inhibited morphine-induced P2X4 receptor expression and blocked anti-nociceptive tolerance to systemically administered morphine. P2X4 receptor asODN treatment also attenuated the morphine-dependent increase of spinal ionized calcium binding protein (Iba1), glial fibrillary acidic protein (GFAP) and mu opioid receptor protein expression. Chronic morphine also decreased perivascular microglial ED2 expression, which was reversed by P2X4 receptor asODN. Together, these data suggest that the modulation of P2X4 receptor expression on microglia and perivascular microglia may prove an attractive target for adjuvant therapy to attenuate opioid-induced anti-nociceptive tolerance. PMID- 20573453 TI - Protective effects of pentoxifylline on the brain following remote burn injury. AB - INTRODUCTION: Brains are often subject to injurious effect following remote burn injury and increased productions of inflammatory cytokines are involved. It is also known that pentoxifylline (PTX) exerts multiple beneficial effects on the inflammatory cascade. Therefore, we investigated whether a single dose of PTX given immediately following severe remote burn would protect the brain from the injurious effects. METHODS: Rats were divided randomly into the sham burn group, burn placebo-treated group and burn PTX-treated group. Single dose of PTX was injected 15 min following initial burn injury. We measured the levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 in the brain tissue at 0.5, 1, 2, 4, 8 and 16 h after burn. Other measures included the level of nuclear factor-kappaB (NF-kappaB) activation, glial activation and apoptosis of cortical cells. RESULTS: PTX substantially suppressed the burn-induced surge in the levels of TNF-alpha, IL-1beta, and IL-6 in the rat-brain tissues. PTX reduced the level of burn-induced apoptosis. PTX also significantly reduced the activation of nuclear transcription factor NF-kappaB and reduced the activation of glial cells in the brain tissue. CONCLUSION: An early, single dose of PTX dramatically reduced brain inflammation and apoptosis for up to 16 h post-injury. PMID- 20573454 TI - Ultrasound assessed thickness of burn scars in association with laser Doppler imaging determined depth of burns in paediatric patients. AB - This study describes the ultrasound assessment of burn scars in paediatric patients and the association of these scar thickness with laser Doppler imaging (LDI) determined burn depth. A total of 60 ultrasound scar assessments were conducted on 33 scars from 21 paediatric burn patients at 3, 6 and 9 months after burn. The mean of peak scar thickness was 0.39+/-0.032 cm, with the thickest at 6 months (0.40+/-0.036 cm). There were 17 scald burn scars (0.34+/-0.045 cm), 4 contact burn scars (0.61+/-0.092 cm), and 10 flame burn scars (0.42+/-0.058 cm). Each group of scars followed normal distributions. Twenty-three scars had original burns successfully scanned by LDI and various depths of burns were presented by different colours according to blood perfusion units (PU), with dark blue <125, light blue 125-250, and green 250-440 PU. The thickness of these scars was significantly different between the predominant colours of burns, with the thinnest scars for green coloured burns and the thickest for dark blue coloured burns. Within light blue burns, grafted burns healed with significantly thinner scars than non-grafted burns. This study indicates that LDI can be used for predicting the risk of hypertrophic scarring and for guiding burn care. To our knowledge, this is the first study to correlate the thickness of burns scars by ultrasound scan with burn depth determined by LDI. PMID- 20573457 TI - Effects of water extract of Urtica dioica L. and modified atmosphere packaging on the shelf life of ground beef. AB - Effects of lyophilized Urtica dioica L. water extract (LUWE) and modified atmosphere packaging (MAP) on the quality and shelf life of ground beef were investigated. Ground beef was stored as aerobic control, MAP (80%O(2)+20% CO(2)), MAP+250 ppm LUWE and MAP and 500 ppm LUWE at 2+/-0.5 degrees C for 14 days. MAP and LUWE had significant effects on mesophilic, psychrotrophic and lactic acid bacteria and Pseudomonas counts. Depending on the level of LUWE, Pseudomonas and psychrotrophic counts decreased. Treatment with 500 ppm LUWE+MAP showed the lowest TBARS values compared to other groups during storage. 80% O(2)-MAP increased TBARS values. Treatment had no significant effect on L* and b* values of the exterior of the ground beef, but had significant effects on the color of interior sections. PMID- 20573456 TI - Evaluation of hygiene practices and microbiological quality of cooked meat products during slicing and handling at retail. AB - Cooked meat ready-to-eat products are recognized to be contaminated during slicing which, in the last years, has been associated with several outbreaks. This work aimed to find out possible relation between the hygiene practice taking place at retail point during slicing of cooked meat products in small and medium sized establishments (SMEs) and large-sized establishments (LEs) and the microbiological quality of sliced cooked meat products. For that, a checklist was drawn up and filled in based on scoring handling practice during slicing in different establishments in Cordoba (Southern Spain). In addition, sliced cooked meats were analyzed for different microbiological indicators and investigated for the presence of Listeria spp. and Listeria monocytogenes. Results indicated that SMEs showed a more deficient handling practices compared to LEs. In spite of these differences, microbiological counts indicated similar microbiological quality in cooked meat samples for both types of establishments. On the other hand, Listeria monocytogenes and Listeria inocua were isolated from 7.35% (5/68) and 8.82% (6/68) of analyzed samples, respectively. Positive samples for Listeria spp. were found in establishments which showed acceptable hygiene levels, though contamination could be associated to the lack of exclusiveness of slicers at retail points. Moreover, Listeria spp presence could not be statistically linked to any microbiological parameters; however, it was observed that seasonality influenced significantly (P<0.05) L. monocytogenes presence, being all samples found during warm season (5/5). As a conclusion, results suggested that more effort should be made to adequately educate handlers in food hygiene practices, focused specially on SMEs. PMID- 20573458 TI - Global comparison of gene expression profiles between intramuscular and subcutaneous adipocytes of neonatal landrace pig using microarray. AB - The objective of this study was to compare the differences of gene expression profiles between intramuscular and subcutaneous adipocytes originated from the isolated preadipocytes in vitro. Cytosolic triglyceride determination indicated that subcutaneous adipocytes accumulated more lipid than intramuscular adipocytes did at the late stage of differentiation. Microarray assay revealed that 172 probes representing 133 genes were differentially expressed, among which 46 genes were highly expressed in intramuscular adipocytes and the other 87 genes were highly expressed in subcutaneous adipocytes. Real-time PCR confirmed that genes related to lipid metabolism, such as LPL, FABP4, FABP5 and OSBPL10, were predominantly expressed in subcutaneous adipocytes, whereas BMP4 and BMP7 were highly expressed in intramuscular adipocytes. The results indicated that the accumulation of lipid mass in subcutaneous adipocytes might be due to the highly expressed genes related to lipid metabolism, and the high levels of BMP4 and BMP7 in intramuscular adipocytes suggested that BMPs might be involved in the differentiation of intramuscular adipocytes. PMID- 20573459 TI - Primary cutaneous blastic plasmacytoid dendritic cell neoplasm without extracutaneous manifestation: case report and review of the literature. AB - Blastic plasmacytoid dendritic cell (BPDC) neoplasm is a rare, highly aggressive hematopoietic malignancy with involvement of bone marrow and peripheral blood. We present 2 cases of primary cutaneous BPDC neoplasm without extracutaneous manifestation during the course of disease. A 36-year-old and a 51-year-old male presented with erythematous patches, purple plaques, and nodules on the head, trunk, and extremities. Skin biopsies revealed that the lesions of both cases were composed of diffusely medium-sized monomorphic blastoid cells infiltrating into the dermis and subcutis. The neoplastic cells were strongly positive for CD4, CD56, CD123, and TdT, whereas other T-cell markers and EBV markers were not expressed. The patients underwent polychemotherapy with hyper-CVAD regimen and obtained a remarkable clinical response with regression of skin lesions. No sign of recurrence and extracutaneous manifestation was found during the period of follow-up. We presume that the favorable prognosis of our cases might result from the presentation only with a skin lesion, diffuse TdT expression in tumor cells, and aggressive chemotherapy with hyper-CVAD regimens. Laboratory examination for blood and bone marrow should be performed every 3-6 months during the first period of follow-up to monitor the progression of disease even if the patients had complete remission at initial chemotherapy. PMID- 20573461 TI - ADHD and genetic syndromes. AB - A high rate of Attention Deficit/Hyperactivity Disorder (ADHD)-like characteristics has been reported in a wide variety of disorders including syndromes with known genetic causes. In this article, we review the genetic and the neurobiological links between ADHD symptoms and some genetic syndromes such as: Fragile X Syndrome, Neurofibromatosis 1, DiGeorge Syndrome, Tuberous Sclerosis Complex, Turner Syndrome, Williams Syndrome and Klinefelter Syndrome. Although each syndrome may arise from different genetic abnormalities with multiple molecular functions, the effects of these abnormalities may give rise to common effects downstream in the biological pathways or neural circuits, resulting in the presentation of ADHD symptoms. Early diagnosis of ADHD allows for earlier treatment, and has the potential for a better outcome in children with genetic syndromes. PMID- 20573460 TI - Capacitation status of stored boar spermatozoa is related to litter size of sows. AB - Semen parameters can be considered useful predictors of sperm fertility. The objective of this study was to address the question of whether differences in in vivo fertility after the use of different ejaculates could be predicted using sperm kinematics, capacitation status, and sperm penetration ability under commercial pig production conditions. The percentage of capacitated sperm, as assessed by chlortetracycline (CTC) staining, was positively correlated with litter size (p<0.01). Our data suggest that litter size increases in proportion to the number of capacitated spermatozoa. When all semen parameters (kinematics, sperm capacitation status, and sperm penetration ability) and litter size were included in a multiple linear regression analysis, significant associations were found between the percentage of capacitated sperm (B-type), the sperm fertility index as assessed by a sperm penetration assay (SPA), and litter size. This relationship between capacitated sperm and litter size, however, was more predictive for smaller litter groups than larger ones. We found that the percentage of B-type sperm was significantly correlated with historic average litter size. However, there was no significant correlation between the percentage of B-type sperm and historic farrowing rates. To determine the normal range for B type sperm, the lower limits were established as 30% for small litters (<8 piglets) and 35% for large litters. The overall accuracy of the assay was 92% and 83% for small and large litters, respectively. These results indicate that capacitation status as measured by CTC staining is a useful predictor of sperm fertility, equivalent to SPA. Moreover, original capacitation status exhibited better predictive ability for small litters than for large ones. Therefore, subfertile boars can be identified primarily by capacitation status. PMID- 20573462 TI - Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation. AB - Demonstrations of the possibility of obtaining functional information from the spinal cord in humans using functional magnetic resonance imaging (fMRI) have been growing in number and sophistication, but the technique and the results that it provides are still perceived by the scientific community with a greater degree of scepticism than fMRI investigations of brain function. Here we review the literature on spinal fMRI in humans during voluntary movements and somatosensory stimulation. Particular attention is given to study design, acquisition and statistical analysis of the images, and to the agreement between the obtained results and existing knowledge regarding spinal cord anatomy and physiology. A striking weakness of many spinal fMRI studies is the use of small numbers of subjects and of time-points in the acquired functional image series. In addition, spinal fMRI is characterised by large physiological noise, while the recorded functional responses are poorly characterised. For all these reasons, spinal fMRI experiments risk having low statistical power, and few spinal fMRI studies have yielded physiologically relevant information. Thus, while available evidence indicates that spinal fMRI is feasible, we are only approaching the stage at which the technique can be considered to have been rigorously established as a viable means of noninvasively investigating spinal cord functioning in humans. PMID- 20573463 TI - Assessment of spatial BOLD sensitivity variations in fMRI using gradient-echo field maps. AB - Clinical blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is becoming increasingly valuable in, e.g., presurgical planning, but the commonly used gradient-echo echo-planar imaging (GE-EPI) technique is sometimes hampered by macroscopic field inhomogeneities. This can affect the degree of signal change that will occur in the GE-EPI images as a response to neural activation and the subsequent blood oxygenation changes, i.e., the BOLD sensitivity (BS). In this study, quantitative BS maps were calculated directly from gradient-echo field maps obtainable on most clinical scanners. In order to validate the accuracy of the calculated BS-maps, known shim gradients were applied and field maps and GE-EPI images of a phantom were acquired. Measured GE EPI image intensity was then compared with the calculated (predicted) image intensity (pII) which was obtained from the field maps using theoretical expressions for image-intensity loss. The validated expressions for pII were used to calculate the corresponding predicted BOLD sensitivity (pBS) maps in healthy volunteers. Since the field map is assumed to be valid throughout an entire fMRI experiment, the influence of subject motion on the pBS maps was also assessed. To demonstrate the usefulness of such maps, pBS was investigated for clinically important functional areas including hippocampus, Broca's area and primary motor cortex. A systematic left/right pBS difference was observed in Broca's area and in the hippocampus, most likely due to magnetic field inhomogeneity of the particular MRI-system used in this study. For all subjects, the hippocampus showed pBS values above unity with a clear anterior-posterior gradient and with an abrupt drop to zero pBS in the anterior parts of hippocampus. It is concluded that GE field maps can be used to accurately predict BOLD sensitivity and that this parameter is useful to assess spatial variations which will influence fMRI experiments. PMID- 20573464 TI - Reliability and reproducibility of perfusion MRI in cognitively normal subjects. AB - Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is becoming a popular method for measuring perfusion due to its ability of generating perfusion maps noninvasively. This allows for frequent repeat scanning, which is especially useful for follow-up studies. However, limited information is available regarding the reliability and reproducibility of ASL perfusion measurements. Here, the reliability and reproducibility of pulsed ASL was investigated in an elderly population to determine the variation in perfusion among cognitively normal individuals in different brain structures. Intraclass correlation coefficients (ICC) and within-subject variation coefficients (wsCV) were used to estimate reliability and reproducibility over a period of 1 year. Twelve cognitively normal subjects (75.5 +/- 5.3 years old, six male and six female) were scanned four times (at 0, 3, 6 and 12 months). No significant difference in cerebral blood flow (CBF) was found over this period. CBF values ranged from 46 to 53 ml/100 g per minute in the medial frontal gyrus (MFG) and from 40 to 44 ml/100 g per minute over all gray matter regions in the superior part of the brain. Data obtained from the first two scans were processed by two readers and showed high reliability (ICC >0.97) and reproducibility (wsCV <6%). However, over the total period of 1 year, reliability reduced to a moderate level (ICC=0.63-0.74) with wsCVs of gray matter, left MFG, right MFG of 13.5%, 12.3%, and 15.4%, respectively. In conclusion, measurement of CBF with pulsed ASL provided good agreement between inter-raters. A moderate level of reliability was obtained over a 1-year period, which was attributed to variance in slice positioning and coregistration. As such pulsed ASL has the potential to be used for CBF comparison in longitudinal studies. PMID- 20573465 TI - Adaptive smoothing of high angular resolution diffusion-weighted imaging data by generalized cross-validation improves Q-ball orientation distribution function reconstruction. AB - Q-ball imaging (QBI) is a high angular resolution diffusion-weighted imaging (HARDI) technique for reconstructing the orientation distribution function (ODF). Some form of smoothing or regularization is typically required in the ODF reconstruction from low signal-to-noise ratio HARDI data. The amount of smoothing or regularization is usually set a priori at the discretion of the investigator. In this article, we apply an adaptive and objective means of smoothing the raw HARDI data using the smoothing splines on the sphere method with generalized cross-validation (GCV) to estimate the diffusivity profile in each voxel. Subsequently, we reconstruct the ODF, from the smoothed data, based on the Funk Radon transform (FRT) used in QBI. The spline method was applied to both simulated data and in vivo human brain data. Simulated data show that the smoothing splines on the sphere method with GCV smoothing reduces the mean squared error in estimates of the ODF as compared with the standard analytical QBI approach. The human data demonstrate the utility of the method for estimating smooth ODFs. PMID- 20573466 TI - Size exclusion chromatography with evaporative light scattering detection as a method for speciation analysis of polydimethylsiloxanes. I: Influence of selected factors on the signal intensity of the detector. AB - Evaporative light scattering detector (ELSD) is widely recognized as a universal tool in chromatography. In this paper, the characteristics of the ELSD detector response and the influence of different factors on the signal intensity are described. Further, results are presented on the influence of some selected factors on the signal intensity and repeatability of results for linear structure polydimethylosiloxanes (PDMS), differing in molecular weight and viscosity. The following factors were studied: (i) the flow velocity of the nebulising gas, (ii) the temperature of the drift tube and the detection cell, and (iii) the flow velocity of the mobile phase, as they all constitute important parameters of the detector. Based on such studies, the optimal parameters of detector indications can be selected for a specific analysis. The results confirmed the possibility to select one set of values for those parameters that allow for analysis of linear PDMS molecules with viscosities ranging from 10 to 60,000 cSt. The following optimal and common parameter values were specified: temperature drift tube 50 degrees C, carrier gas pressure (for nebulisation) 140 kPa, and mobile phase flow rate 0.7 ml/min. A high repeatability of the results was demonstrated as the relative standard deviation was less than 2.5%. This type of tests for polydimethylosiloxanes has not been presented in any previous publication. PMID- 20573467 TI - A new computer-based counselling system for the promotion of physical activity in patients with chronic diseases--results from a pilot study. AB - OBJECTIVE: To develop a computer-based counselling system (CBCS) for the improvement of attitudes towards physical activity in chronically ill patients and to pilot its efficacy and acceptance in primary care. METHODS: The system is tailored to patients' disease and motivational stage. During a pilot study in five German general practices, patients answered questions before, directly and 6 weeks after using the CBCS. Outcome criteria were attitudes and self-efficacy. Qualitative interviews were performed to identify acceptance indicators. RESULTS: Seventy-nine patients participated (mean age: 64.5 years, 53% males; 38% without previous computer experience). Patients' affective and cognitive attitudes changed significantly, self-efficacy showed only minor changes. Patients mentioned no difficulties in interacting with the CBCS. However, perception of the system's usefulness was inconsistent. CONCLUSION: Computer-based counselling for physical activity related attitudes in patients with chronic diseases is feasible, but the circumstances of use with respect to the target group and its integration into the management process have to be clarified in future studies. PRACTICE IMPLICATION: This study adds to the understanding of computer-based counselling in primary health care. Acceptance indicators identified in this study will be validated as part of a questionnaire on technology acceptability in a subsequent study. PMID- 20573468 TI - Cognitive-emotional decision making (CEDM): a framework of patient medical decision making. AB - OBJECTIVE: Assistance for patients faced with medical decisions has largely focussed on the clarification of information and personal values. Our aim is to draw on the decision research describing the role of emotion in combination with health behaviour models to provide a framework for conceptualizing patient decisions. METHODS: A review of the psychological and medical decision making literature concerned with the role of emotion/affect in decision making and health behaviours. RESULTS: Emotion plays an influential role in decision making. Both current and anticipated emotions play a motivational role in choice. Amalgamating these findings with that of Leventhal's (1970) SRM provide a framework for thinking about the influence of emotion on a patient medical decision. CONCLUSION: Our framework suggests that a patient must cope with four sets of elements. The first two relate to the need to manage the cognitive and emotional aspects of the health threat. The second set relate to the management of the cognitive and emotional elements of the decision, itself. PRACTICE IMPLICATIONS: The framework provides a way for practitioners and researchers to frame thinking about a patient medical decision in order to assist the patient in clarifying decisional priorities. PMID- 20573469 TI - Desmuslin gene knockdown causes altered expression of phenotype markers and differentiation of saphenous vein smooth muscle cells. AB - OBJECTIVE: Phenotypic alterations of vascular smooth muscle cells (VSMCs) appear critical to the development of primary varicose veins. Previous study indicated desmuslin, an intermediate filament protein, was differentially expressed in smooth muscle cells (SMCs) isolated from varicose veins; thus, it was naturally hypothesized that altered desmuslin expression might in turn affect the functioning of VSMCs, leading to the phenotypic alterations and varicose vein development. METHODS: In this study, expression of desmuslin in normal human saphenous vein SMCs was knocked down using small interfering RNA (siRNA), and control cells were treated with a scrambled siRNA sequence. The levels of several phenotypic markers including smooth muscle (SM) alpha-actin and smooth muscle myosin heavy chain (SM-MHC) were assessed. Collagen formation, matrix metalloproteinase expression (MMP-2), and cytoskeletal and morphological changes were also examined. RESULTS: SMCs treated with desmuslin siRNA exhibited significantly increased levels of collagen synthesis and MMP-2 expression and decreased expression levels of SM alpha-actin, SM-MHC, and smoothelin and exhibited disassembly of actin stress fibers when compared with the control cells. Changes in cell morphology and actin fiber networks in VSMCs treated with desmuslin siRNA were consistent with a lower degree of differentiation. CONCLUSIONS: These results indicated desmuslin expression is required for the maintenance of VSMC phenotype. Decreased desmuslin expression may affect differentiation of VSMCs and ultimately contribute to the development of varicose veins. PMID- 20573470 TI - Oxidized LDL in human carotid plaques is related to symptomatic carotid disease and lesion instability. AB - BACKGROUND: Oxidative stress is an important determinant in atherosclerosis development. Various markers of oxidative stress, such as oxidation of low density lipoprotein (LDL), nitrosative stress, lipid peroxidation, and protein oxidation, have been implicated in the initiation and/or progression of atherosclerosis, but their association with plaque erosion and symptomatic carotid disease has not been fully defined. In addition, certain oxidative markers have been shown in various models to promote plaque remodeling through matrix metalloproteinase (MMP) activation. OBJECTIVE: To perform a global investigation of various oxidative stress markers and assess for potential relationships with destabilization and symptomatic development in human carotid plaques. METHODS: Thirty-six patients undergoing endarterectomy were evaluated and compared with 20 control specimens obtained at the time of autopsy. Differences between stable and unstable plaques, symptomatic and asymptomatic patients, and >or=90% and <90% stenosis were evaluated. Oxidized LDL (ox-LDL), nitrotyrosine (NT), malondialdehyde (MDA), and protein carbonyls (PCs) levels were determined in atheromatic plaques homogenates by corresponding biochemical assays. Immunohistochemical (IHC) analysis was also employed to determine the percentage and topological distribution of cells expressing NT and metalloproteinase-9 (MMP-9) in serial sections from corresponding atheromatic plaques. MMP-9 expression was further verified using Western blot analysis. RESULTS: Ox-LDL was increased in symptomatic patients (P < .05). Also, ox-LDL and NT levels were significantly higher in unstable versus stable carotid plaques (P < .05, respectively). Furthermore, IHC serial section analysis, corroborated by statistical analysis, showed a topological and expressional correlation between NT and MMP-9 (P < .05). MDA and PCs levels, although increased in carotid plaques, did not distinguish stable from unstable carotid plaques as well as symptomatic from asymptomatic patients with various degrees of stenosis. CONCLUSION: All types of investigated oxidative stress markers were significantly increased in human carotid plaques, but only ox-LDL levels were associated with clinical symptoms, while peroxynitrite products and MMP-9 were specifically related to plaque instability. PMID- 20573471 TI - Nanoparticle-mediated endothelial cell-selective delivery of pitavastatin induces functional collateral arteries (therapeutic arteriogenesis) in a rabbit model of chronic hind limb ischemia. AB - OBJECTIVES: We recently demonstrated in a murine model that nanoparticle-mediated delivery of pitavastatin into vascular endothelial cells effectively increased therapeutic neovascularization. For the development of a clinically applicable approach, further investigations are necessary to assess whether this novel system can induce the development of collateral arteries (arteriogenesis) in a chronic ischemia setting in larger animals. METHODS: Chronic hind limb ischemia was induced in rabbits. They were administered single injections of nanoparticles loaded with pitavastatin (0.05, 0.15, and 0.5 mg/kg) into ischemic muscle. RESULTS: Treatment with pitavastatin nanoparticles (0.5 mg/kg), but not other nanoparticles, induced angiographically visible arteriogenesis. The effects of intramuscular injections of phosphate-buffered saline, fluorescein isothiocyanate (FITC)-loaded nanoparticles, pitavastatin (0.5 mg/kg), or pitavastatin (0.5 mg/kg) nanoparticles were examined. FITC nanoparticles were detected mainly in endothelial cells of the ischemic muscles for up to 4 weeks. Treatment with pitavastatin nanoparticles, but not other treatments, induced therapeutic arteriogenesis and ameliorated exercise-induced ischemia, suggesting the development of functional collateral arteries. Pretreatment with nanoparticles loaded with vatalanib, a vascular endothelial growth factor receptor (VEGF) tyrosine kinase inhibitor, abrogated the therapeutic effects of pitavastatin nanoparticles. Separate experiments with mice deficient for VEGF receptor tyrosine kinase demonstrated a crucial role of VEGF receptor signals in the therapeutic angiogenic effects. CONCLUSIONS: The nanotechnology platform assessed in this study (nanoparticle-mediated endothelial cell-selective delivery of pitavastatin) may be developed as a clinically feasible and promising strategy for therapeutic arteriogenesis in patients. PMID- 20573472 TI - The influence of Dominique Jean Larrey on the art and science of amputations. PMID- 20573473 TI - Mechanisms of gender-related outcome differences after carotid endarterectomy. AB - OBJECTIVE: Large randomized trials have confirmed a difference in outcome after carotid endarterectomy (CEA) between men and women. In this review, we aimed to provide an overview of the gender-specific characteristics causing these perioperative and long-term outcome differences between men and women after CEA. METHODS: A systematic search strategy with the synonyms of 'gender' and 'carotid endarterectomy' was conducted from PubMed and EMBASE databases. Only 11 relevant studies specifically discussing gender-specific related characteristics and their influence on outcome after CEA could be identified. RESULTS: Due to the limited number of included studies, pooling of findings was impossible, and results are presented in a descriptive manner. Each included study described only one possible gender-specific factor. Differences in carotid artery diameter, sex hormones, sensitivity for antiplatelet therapy, plaque morphology, occurrence of microembolic signals, and restenosis rate have all been suggested as gender specific characteristics influencing outcome after CEA. CONCLUSION: Higher embolic potential in women and relatively stable female plaque morphology are the best-described factors influencing the difference in outcomes between men and women. However, the overall evidence for outcome differences by gender-specific characteristics in the literature is limited. PMID- 20573474 TI - Long-term outcomes of surgical aortic fenestration for complicated acute type B aortic dissections. AB - INTRODUCTION: Surgical aortic fenestration has been used for treating ischemic complications of acute type B aortic dissection (ABAD). In the current endovascular era, surgical aortic fenestration may serve as an alternative for these patients after percutaneous failure. The purpose of this study is to describe our surgical suprarenal and infrarenal aortic fenestration technique, and to report the long-term outcomes of this approach in the management of complicated ABAD. METHODS: We retrospectively analyzed the in-hospital and long term outcomes of 18 patients treated with either suprarenal (n = 10) or infrarenal surgical fenestration (n = 8) for complicated ABAD between 1988 and 2002. Suprarenal fenestration was performed through a thoracoabdominal incision in the 10th intercostal space, whereas patients treated with infrarenal fenestration underwent a midline laparotomy. A longitudinal aortotomy was performed and the true and false lumens were identified, followed by a wide resection of the intimal membrane. RESULTS: Median age was 60 years (range, 48-82 years) and 89% (n = 16) were male. The in-hospital mortality was 22% (n = 4), which included two deaths after suprarenal fenestration and two deaths after infrarenal fenestration. In the remaining patients, full visceral, renal, and lower extremity function was recovered, except for 1 patient with paraplegia at admission in which the neurologic deficit was permanent. Median follow-up of the surviving patients was 10.0 years (interquartile range, 12.5; range, 0.5-20 years). During follow-up, none of the patients developed renal or visceral ischemia, or ischemic complications to the lower extremities, and no significant dilatations of the treated aortic segments were noted. Three of 14 patients with ABAD who were discharged alive expired during the follow-up period due to causes unrelated to the surgical procedure. CONCLUSION: Surgical aortic fenestration represents an effective and durable option for treating ischemic complications of ABAD. Actually, this conservative surgical technique may serve as the alternative treatment in case of contraindications or failure of endovascular management of complicated ABAD. PMID- 20573475 TI - An elevated neutrophil-lymphocyte ratio independently predicts mortality in chronic critical limb ischemia. AB - BACKGROUND: Atherogenesis represents an active inflammatory process with leucocytes playing a major role. An elevated white blood cell count has been shown to be predictive of death in coronary artery disease patients. The aim of this study was to examine the predictive ability of neutrophil count and neutrophil/lymphocyte ratio for predicting survival in patients with critical lower limb ischemia (CLI). METHODS: All patients admitted to a single vascular unit with CCLI were identified prospectively over a 2-year period starting from January 2005. Patient demographics, clinical history, comorbidity, and risk factors for peripheral vascular disease were documented. The white blood count and differential cell count at admission was recorded. Overall, patient mortality was studied as the primary outcome. RESULTS: One hundred forty-nine patients were identified, with a median age of 72 years (Interquartile range [IQR], 65.7-81). A neutrophil-lymphocyte ratio (NLR) of >or=5.25 was taken as the cutoff, based upon the receiver-operating-characteristic.The median follow up was 8.7 months (IQR, 3.1-16). During the follow-up period, there have been 62 deaths (43.4%). An elevated neutrophil/lymphocyte ratio and a high troponin level (>0.1) were found to be the only two factors independently associated with shorter survival on multivariate analysis using the Cox proportional hazards model. CONCLUSIONS: This study suggests that an elevated NLR can identify a poor-risk subset of patients among those being treated for critical limb ischemia. This simple, inexpensive test may, therefore, add to risk stratification of these high-risk patients. PMID- 20573476 TI - Mid-term clinical outcome and predictors of vessel patency after femoropopliteal stenting with self-expandable nitinol stent. AB - BACKGROUND: Long-term clinical outcomes after femoropopliteal (FP) stenting with nitinol stents have not yet been clear. We investigated the mid-term efficacy of FP stenting with nitinol stents. METHODS: This study was a multicenter retrospective study. From April 2004 to December 2008, 511 consecutive patients (639 limbs; mean age 71 +/- 7 years; 71% male) who underwent successful FP stenting with nitinol stents for de novo lesions were retrospectively selected and analyzed in this multicenter study. All patients had a minimum follow-up of 6 months. Restenosis was defined as >2.4 of peak systolic velocity ratio by duplex or >50% stenosis by angiogram. Primary patency was defined as treated vessels without restenosis and repeat revascularization. Secondary patency was defined as target vessels that become totally occluded and are reopened by repeat revascularization. RESULTS: Sixty-one percent of the patients had diabetes, 76% were claudicant, and 20% were on hemodialysis. Mean lesion length was 151 +/- 75 mm. Mean follow-up period was 22 +/- 11 months. Primary patency was 79.8%, 66.7%, and 63.1%, and secondary patency was 90.4%, 87.3%, and 86.2% at 1, 3, and 5 years, respectively. During the follow-up period, 53 patients (10%) died. Of them, cardiovascular death was 38% and stent fracture had occurred in 14%. On multivariate analysis by Cox proportional hazard ratio, cilostazol administration (hazard ratio [HR], 0.52;P < .0001), stent fracture (HR, 1.6; P = .03), hemodialysis (HR, 1.7; P = .01), and Trans Atlantic Inter-Society Consensus (TASC) II class C/D (HR, 2.4; P < .0001) were the independent predictors of primary patency after successful FP stenting. CONCLUSION: Clinical efficacy of nitinol stent implantation for FP disease was favorable for up to 5 years. PMID- 20573478 TI - Practical use of duplex echo-guided recanalization of chronic total occlusion in the iliac artery. AB - Although endovascular therapy for peripheral arterial disease has undergone tremendous changes, chronic total occlusion (CTO) remains a significant challenge for interventionalists. Failed CTO recanalization is predominately due to unsuccessful guidewire crossing. In particular, the unique characteristics of tortuous and deeply located large vessels in the retroperitoneal cavity create challenging endovascular procedures. Real-time guidance based on external direct vessel visualization might be a promising tool for successful recanalization of noncalcific CTO. Here, we describe the practical use of duplex echo-guidance during the procedural course of iliac CTO recanalization. PMID- 20573477 TI - Rationale and practical techniques for mouse models of early vein graft adaptations. AB - Mouse models serve as relatively new yet powerful research tools to study intimal hyperplasia and wall remodeling of vein bypass graft failure. Several model variations have been reported in the past decade. However, the approach demands thoughtful preparation, selected sophisticated equipment, microsurgical technical expertise, advanced tissue processing, and data acquisition. This review compares several described models and aims (building on our personal experiences) to practically aid the investigators who want to utilize mouse models of vein graft failure. PMID- 20573479 TI - CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients. PMID- 20573480 TI - [Thrombosis valvular prosthesis of Starr treated successfully by tenecteplase during pregnancy]. PMID- 20573481 TI - Expectations, validity, and reality in omics. AB - Diverse methods of large-scale measurements of biological processes have emerged in the last 15 years and their list is growing rapidly. Almost invariably, these advances in omics have been associated with major expectations of transforming not only biological knowledge but also medicine and health. However, practical applications of omics in biomedicine have often suffered from poor attention to issues of validity. As a consequence, major promises of personalized medicine have not yet materialized in improving patient or population outcomes. Several omics fields increasingly realize the need to safeguard the validity of their efforts, make reporting more transparent, and improve the translational potential of their studies. Many discoveries point indeed toward a highly individualized profile of health and disease, where each case is different, but this is currently difficult to translate into more effective personalized treatment or prevention. Given the exponential growth of collected data, understanding is often drowning in the sea of measurements. PMID- 20573482 TI - Assessing the impact of attrition in randomized controlled trials. AB - OBJECTIVES: A survey of randomized controlled trials found that almost a quarter of trials had more than 10% of responses missing for the primary outcome. There are a number of ways in which data could be missing: the subject is unable to provide it, or they withdraw, or become lost to follow-up. Such attrition means that balance in baseline characteristics for those randomized may not be maintained in the subsample who has outcome data. For individual trials, if the attrition is systematic and linked to outcome, then this will result in biased estimates of the overall effect. It then follows that if such trials are combined in a meta-analysis, it will result in a biased estimate of the overall effect and be misleading. The aim of this study was to investigate the impact of attrition on baseline imbalance within individual trials and across multiple trials. STUDY DESIGN AND SETTING: In this article, we used individual patient data from a convenience sample of 10 trials evaluating interventions for the treatment of musculoskeletal disorders. Meta-analyses using the mean difference at baseline between the trial arms were carried out using individual patient data from these trials. The analyses were first carried out using all randomized participants and secondly only including participants with outcome data on the quality-of-life score. Meta-regression was carried out to evaluate whether the level of baseline imbalance was associated with the level of attrition. RESULTS: The overall attrition rates for the quality-of-life score ranged between 4% and 28% of the total randomized patients. All trials showed some level of differential attrition between the treatment arms, ranging from 1% to 14%. Attrition within the control group ranged from 3% to 25% and within the intervention group, it ranged from 0% to 31%. For individual trials, there was no indication that attrition altered the results in favor of either the treatment or the control. Forest plots highlighted that the attrition had some impact on the baseline imbalance for the primary outcome score as more heterogeneity was introduced (I-squared value of 0.4% for the initial data set vs. I-squared value of 16.9% for the analyzed data set). However, the standardized mean difference increased only slightly (from 0.01 to 0.03 with 95% confidence interval [CI]: -0.05, 0.10). Meta-regression showed little or no evidence of a significant dose-response relationship between the level of attrition and the baseline imbalance (coefficient 0.73, 95% CI: -0.81, 2.28). CONCLUSION: Although, in theory, attrition can introduce selection bias in randomized trials, we did not find sufficient evidence to support this claim in our convenience sample of trials. However, the number of trials included was relatively small, which may have led to small but important differences in outcomes being missed. In addition, only 2 of 10 trials included had attrition levels greater than 15% suggesting a low level of potential bias. Meta-analyses and systematic reviews should always consider the impact of attrition on baseline imbalances and where possible any baseline imbalances in the analyzed data set and their impact on the outcomes reported. PMID- 20573483 TI - Empirical assessment suggests that existing evidence could be used more fully in designing randomized controlled trials. AB - BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) provide the highest level of evidence regarding the effectiveness of interventions. Less is known about how they are used to inform the design and reporting of RCTs. METHODS: A sample of RCTs published in leading medical journals in 2007 was assessed to establish whether authors considered previous trials in the design of their trial. An approach to calculate the sample size required for a significant pooled effect in an updated meta-analysis was applied to a subsample of the RCTs to illustrate the ways in which the results of an existing meta-analysis can be incorporated into the planning and reporting of new RCTs. RESULTS: Six of the 27 trials assessed (22%) reported the use of previous trial(s) for sample size calculations. Meta-analyses relating the results of the trial to previous research were cited in 37% (10 out of 27) of the report discussion sections. Previous evidence is formally incorporated into retrospective sample size calculations for three of the trials. DISCUSSION/CONCLUSION: Consulting previous research before embarking on a new trial and basing decisions about future research on the impact on an updated meta-analysis will make the reporting of research more coherent and the design of new RCTs more efficient. PMID- 20573485 TI - Learning from the past: refining the way we study treatments. PMID- 20573484 TI - A simple method for calculating power based on a prior trial. AB - OBJECTIVE: When an investigator wants to base the power of a planned clinical trial on the outcome of another trial, the latter study may not have been reported in sufficient detail to allow this. For example, when the outcome is a change from baseline, the power calculation requires the standard deviation of the difference, and it frequently happens that only the standard deviations of the baseline and the follow-up measurements are reported. Also when a complex analysis or an analysis with covariates is planned, the power calculation may be difficult or impossible. The objective was to develop a method to determine the power of a trial, based on minimal information from a previous (reference) trial. STUDY DESIGN AND SETTING: We investigated the power calculation for a range of statistical methods, including the t-test, analysis of covariance, analysis of variance, linear regression, logistic regression, Poisson regression, the Wilcoxon test, and the logrank test. RESULTS: A method to calculate the power of a trial solely based on the P-value or the confidence interval of the outcome of the reference study. CONCLUSION: A power calculation based on an earlier similar trial only requires its P-value. PMID- 20573487 TI - Microchimerism in psoriasis vulgaris: A preliminary report. PMID- 20573486 TI - Clinical manifestations and effects of primary percutaneous coronary intervention for patients with delayed pre-hospital time in acute myocardial infarction. AB - BACKGROUND: Prolonged pre-hospital time for acute myocardial infarction (AMI) is associated with decreased indication for primary percutaneous coronary intervention (PCI). However, the efficacy of primary PCI in AMI patients with prolonged pre-hospital time has not been fully investigated in Japan. METHODS AND RESULTS: A total of 3010 consecutive AMI patients admitted to AMI-Kyoto Multi Center Risk Study Group hospitals were retrospectively analyzed, and the clinical characteristics and in-hospital prognosis of these patients were reviewed. Patients with pre-hospital delay [elapsed time (ET)>12 h] had a lower frequency of Killip>=3 (9.3%) and less frequently received primary PCI (77.7%) compared with patients with ET<=12 h. In the ET>12 h group, older patients or patients with MI history tended to be complicated by heart failure. Primary PCI was performed for patients with ET>12 h, irrespective of the severity of heart failure [Killip 1 (78.7%) vs Killip>=2 (74.0%); p=0.3827]. On multivariate logistic regression analysis, age [odds ratio (OR) 1.053], MI history (OR 2.860), Killip>=2 (OR 10.235), and multi-vessels or left main coronary artery as culprit (OR 11.712) were significant independent positive predictors of in-hospital mortality for patients with ET>12 h. Practice of primary PCI was not a significant negative predictor for patients with ET>12 h (OR 0.812), but it was for patients with ET<=12 h (OR 0.425). CONCLUSIONS: These findings indicate that patients with ET>12 h have a less severe condition and less frequently receive primary PCI compared with patients with ET<=12 h. Although primary PCI is often performed for these patients irrespective of the severity of heart failure, no preferable effect of primary PCI on the in-hospital mortality is demonstrated. In contrary, practice of primary PCI is a significant negative predictor of in hospital mortality for patients with ET<=12 h. PMID- 20573488 TI - Operator-based Floquet theory in solid-state NMR. AB - This article reviews the application of operator-based Floquet theory in solid state NMR. Basic expressions for calculating effective Hamiltonians based on van Vleck perturbation theory are reviewed for problems with a single frequency or multiple incommensurate frequencies. Such a treatment allows calculation of effective Hamiltonians for resonant and non-resonant problems. Examples from literature are given for single-mode to triple-mode Floquet problems, covering a wide range of applications in solid-state NMR under magic-angle spinning and radio-frequency irradiation of a single nucleus or multiple nuclei. PMID- 20573489 TI - [Borrelia-associated lymphocytoma cutis]. AB - We describe a 6-year-old boy who developed Borrelia burgdorferi-associated lymphocytoma cutis on the ear. Lymphocytoma is a benign polyclonal B-cell lymphoproliferative process; it is defined as a subacute manifestation of early disseminated borrelial infection. Clinical history, physical examination, and serodiagnosis tests are often sufficient to establish diagnosis, but sometimes, histopathologic analysis is needed to exclude malignant cutaneous lymphomas. The outcome is always favorable but after antibiotic therapy, the lesion disappears promptly. PMID- 20573491 TI - A 'natural' way to provide innate mucosal immunity. AB - The mucosal barrier comprises a layered defense system including physio-chemical and immunological strategies to contain commensal microflora while protecting the host against potential pathogens. In contrast to the clearly established and well characterized role for the adaptive immune system in intestinal defense, our knowledge on innate immune mechanisms that operate in the gut is much less defined. The recent identification of novel innate lymphoid cells (ILC), including 'NK-like' cells that naturally produce IL-22 and appear to play a role in intestinal defense, demonstrates an unexpected and increasing complexity in mucosal innate immunity. PMID- 20573490 TI - Omega-3 long chain fatty acid synthesis is regulated more by substrate levels than gene expression. AB - The conversion of linoleic acid (LA) and alpha-linolenic acid (ALA) to long chain polyunsaturated fatty acids (LCPUFA) is known to involve desaturation and elongation steps. Although there is evidence that genes for these steps can be regulated by extremes of dietary PUFA, the degree to which there is meaningful regulation of LCPUFA levels in tissues by diet as a result of changes in expression of desaturase and elongase genes is unclear. In this study, we tested the effect of increasing ALA levels in diets of rats from 0.2% to 2.9% energy (en) against a constant LA level (1%en) on plasma and liver phospholipid LCPUFA content together with the expression of hepatic genes involved in PUFA metabolism, the desaturases FADS1 and FADS2, the elongases ELOV2 and ELOV5, and the transcription factors sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARalpha). The levels of plasma and liver eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) increased in proportion to dietary ALA whereas docosahexaenoic acid (DHA) increased only up to 1%en ALA. A low PUFA (0.4%en) reference diet stimulated the expression of delta 6 desaturase (FADS2) and elongase 2 (ELOVL2) when compared to higher PUFA diets. There was, however, no difference in the expression of any of the genes in rats, which were fed diets containing between 0.2%en and 2.9%en ALA and mRNA expression was unrelated to tissue/plasma LCPUFA content. These data suggest that the endogenous synthesis of n-3 LCPUFA from the precursor ALA is regulated independently of changes in the expression of the synthetic enzymes or regulatory transcription factor, and provides evidence that n-3 LCPUFA synthesis is regulated more by substrate competition for existing enzymes than by an increase in their mRNA expression. PMID- 20573492 TI - Chinese herbs in treatment of influenza: a randomized, double-blind, placebo controlled trial. AB - OBJECTIVE: To investigate the efficacy and safety of Antiwei, a traditional Chinese prescription, in the treatment of influenza. METHODS: In a multi-center, randomized, double-blind, placebo-controlled trial, we recruited 480 adults aged 18 to 65 years within 36 h of onset of influenza-like symptoms. There were 225 patients with confirmed influenza. Eligible patients were randomly assigned 6 g of Antiwei (n = 360) or placebo (n = 120) twice daily for three days. All patients recorded their temperature and symptoms on diary cards during treatment. Analyses were performed in both the influenza-like population and the influenza confirmed population. RESULTS: Antiwei increased patients' recovery by 17% (P < 0.001), and reduced the severity of illness measured by the median symptom score by 50% (P < 0.001) in both the influenza-like and the influenza-confirmed populations, compared to placebo. The influenza-confirmed patients reported reductions in the severity of fever (P = 0.002), cough (P = 0.023) and expectoration (P = 0.004) after one-day of treatment with Antiwei, compared to placebo. The adverse event profiles were similar for Antiwei and placebo. CONCLUSION: Antiwei was effective and well tolerated in treatment of natural influenza infection in adults. Antiwei represents a clinically valuable intervention in the management of influenza. PMID- 20573493 TI - Docosahexaenoic acid attenuates VCAM-1 expression and NF-kappaB activation in TNF alpha-treated human aortic endothelial cells. AB - This study was conducted to test the hypothesis that n-3 polyunsaturated fatty acids are able to down-regulate expression of adhesion molecules and nuclear factor-kappaB (NF-kappaB) activation in vascular endothelial cells, in addition to reducing atherosclerotic lesions in vivo. We report here that docosahexaenoic acid (DHA) reduces atherosclerotic lesions in the aortic arteries of apolipoprotein E knockout (apoE(-/-)) mice. Consistent with the observation in animal study, DHA inhibited THP-1 cell adhesion to tumor necrosis factor alpha (TNF-alpha)-activated human aortic endothelial cells (HAECs). Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) on the cell surface of HAECs was determined by cell-surface enzyme linked immunosorbent assay. DHA and eicosapentaenoic acid decreased VCAM-1 expression in a dose-dependent manner in TNF-alpha treated HAECs, while cis linoleic acid and arachidonic acid did not have any significant effect on either VCAM-1 or ICAM-1 expression. Moreover, DHA significantly reduced VCAM-1 protein expression in the cell lysates of TNF-alpha-treated HAECs, as determined by Western blot analysis. In line with NF-kappaB signaling pathway, DHA suppressed the TNF-alpha-activated IkappaBalpha phosphorylation and degradation as well as IkappaB kinase-beta phosphorylation. Subsequently, translocation of the NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun) subunits was down-regulated by DHA in the nucleus of HAECs. These results suggest that DHA negatively regulates TNF-alpha induced VCAM-1 expression through attenuation of NF-kappaB signaling pathway and AP-1 activation. This study provides evidence that DHA may contribute to the prevention of atherosclerosis and inflammatory diseases in vivo. PMID- 20573494 TI - Effects of glutamine administration on inflammatory responses in chronic ethanol fed rats. AB - The purpose of this study was to investigate the effects of glutamine supplementation on inflammatory responses in chronic ethanol-fed rats. Male Wistar rats weighing about 160 g were divided into five groups. Two groups were fed a normal liquid diet and three groups were fed a glutamine-containing liquid diet. After 1 week, one of the normal liquid diet groups was fed an ethanol containing liquid diet (CE), and the other group served as the control (CC) group. At the same time, one of the glutamine-containing liquid diet groups was continually fed the same diet (GCG), but the other two groups were fed ethanol containing diet supplemented with glutamine (GEG) or without glutamine (GE). The following items were analyzed: (1) liver function, (2) cytokine contents, and (3) hepatic oxidative stress. The activities of aspartate transaminase (AST) and alanine transaminase (ALT) and levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in the CE group had significantly increased. In addition, hepatic cytochrome P450 2E1 (CYP2E1) expression had significantly increased in the CE, GE and GEG groups. However, the activities of AST and ALT and levels of TNF-alpha and IL-1beta in the GE group were significantly lower than those of the CE group. The results suggest that the plasma inflammatory responses of rats fed an ethanol-containing liquid diet for 7 weeks significantly increased. However, pretreatment with glutamine improved the plasma inflammatory responses induced by ethanol. PMID- 20573495 TI - Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-kappaB nuclear binding and increase in PPARgamma expression. AB - It is now well accepted that oxysterols play important roles in the formation of atherosclerotic plaque, involving cytotoxic, pro-oxidant and proinflammatory processes. It has been recently suggested that tomato lycopene may act as a preventive agent in atherosclerosis, although the exact mechanism of such a protection is not clarified. The main aim of this study was to investigate whether lycopene is able to counteract oxysterol-induced proinflammatory cytokines cascade in human macrophages, limiting the formation of atherosclerotic plaque. Therefore, THP-1 macrophages were exposed to two different oxysterols, such as 7-keto-cholesterol (4-16 MUM) and 25-hydroxycholesterol (2-4 MUM), alone and in combination with lycopene (0.5-2 MUM). Both oxysterols enhanced pro inflammatory cytokine [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha) secretion and mRNA levels in a dose-dependent manner, although at different extent. These effects were associated with an increased reactive oxygen species (ROS) production through an enhanced expression of NAD(P)H oxidase. Moreover, a net increment of phosphorylation of extracellular regulated kinase 1/2, p-38 and Jun N-terminal kinase and of nuclear factor kB (NF-kappaB) nuclear binding was observed. Lycopene prevented oxysterol-induced increase in pro inflammatory cytokine secretion and expression. Such an effect was accompanied by an inhibition of oxysterol-induced ROS production, mitogen-activated protein kinase phosphorylation and NF-kappaB activation. The inhibition of oxysterol induced cytokine stimulation was also mimicked by the specific NF-kappaB inhibitor pyrrolidine dithiocarbamate. Moreover, the carotenoid increased peroxisome proliferator-activated receptor gamma levels in THP-1 macrophages. Taken all together, these data bring new information on the anti-atherogenic properties of lycopene, and on its mechanisms of action in atherosclerosis prevention. PMID- 20573496 TI - Anti-obesity effect of carboxymethyl chitin by AMPK and aquaporin-7 pathways in 3T3-L1 adipocytes. AB - The aim of this study was to investigate the anti-obesity effect of carboxymethyl chitin (CM-chitin), a water-soluble derivative of chitin, by measuring lipid accumulation and adipogenesis related factors in 3T3-L1 adipocytes. CM-chitin was synthesized by means of carboxymethylation reaction. Its inhibitory effect on lipid accumulation was investigated by measuring triglyceride content and glycerol release level. The gene and protein levels associated with adipogenesis were determined using reverse transcriptase-polymerase chain reaction and Western blot analysis. Treatment with CM-chitin reduced triglyceride content and enhanced glycerol secretion in a dose-dependent manner. CM-chitin induced the down regulation of adipogenesis related transcriptional factors and adipocyte specific gene promoters. Moreover, the specific mechanism by CM-chitin was confirmed by transcriptional activations of the phosphorylated adenosine monophosphate activated protein kinase (AMPK) and aquaporin-7. These results suggest that CM chitin exerts anti-adipogenic effect on lipid accumulation through modulations of AMPK and aquaporin-7 signal pathways. PMID- 20573497 TI - DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer's disease models. AB - Late-onset Alzheimer's disease seems to be a multi-factorial disease with both genetic and non-genetic, environmental, possible causes. Recently, epigenomics is achieving a major role in Alzheimer's research due to its involvement in different molecular pathways leading to neurodegeneration. Among the different epigenetic modifications, DNA methylation is one of the most relevant to the disease. We previously demonstrated that presenilin1 (PSEN1), a gene involved in amyloidogenesis, is modulated by DNA methylation in neuroblastoma cells and Alzheimer's mice in an experimental model of nutritionally altered one-carbon metabolism. This alteration, obtained by nutritional deficiency of B vitamins (folate, B12 and B6) hampered S-adenosylmethionine (SAM)-dependent methylation reactions. The aim of the present paper was to investigate the regulation of DNA methylation machinery in response to hypomethylating (B vitamin deficiency) and hypermethylating (SAM supplementation) alterations of the one-carbon metabolism. We found that DNA methylases (DNMT1, 3a and 3b) and a putative demethylase (MBD2) were differently modulated, in line with the previously observed changes of PSEN1 methylation pattern in the same experimental conditions. PMID- 20573498 TI - Environmental impacts of post-consumer material managements: recycling, biological treatments, incineration. AB - The environmental impacts of recycling, mechanical biological treatments (MBT) and waste-to-energy incineration, the main management strategies to respond to the increasing production of post-consumer materials are reviewed and compared. Several studies carried out according to life-cycle assessment (LCA) confirm that the lowest environmental impact, on a global scale, is obtained by recycling and by biological treatments (composting and anaerobic fermentations) if compost is used in agriculture. The available air emission factors suggest that, on a local scale, mechanical biological treatments with energy recovery of biogas, may be intrinsically safer than waste-to-energy incinerators. Several studies confirm the capability of biological treatments to degrade many toxic xenobiotic contaminating urban wastes such as dioxins and polycyclic aromatic hydrocarbons, an important property to be improved, for safe agricultural use of compost. Further LCA studies to compare the environmental impact of MBTs and of waste-to energy incinerators are recommended. PMID- 20573499 TI - Plant stomata: a checkpoint of host immunity and pathogen virulence. AB - Stomata are microscopic pores formed by pairs of guard cells in the epidermis of terrestrial plants; they are essential for gas exchange with the environment and controlling water loss. Accordingly, plants regulate stomatal aperture in response to environmental conditions, such as relative humidity, CO(2) concentration, and light intensity. Stomatal openings are also a major route of pathogen entry into the plant and plants have evolved mechanisms to regulate stomatal aperture as an immune response against bacterial invasion. In this review, we highlight studies that begin to elucidate signaling events involved in bacterium-triggered stomatal closure and discuss how pathogens may have exploited environmental conditions or, in some cases, have evolved virulence factors to actively counter stomatal closure to facilitate invasion. PMID- 20573500 TI - Post-traumatic acute hallux valgus: a case report. AB - Hallux valgus and tibial fractures are common conditions in trauma and orthopaedics. To date, there has been no report of acute hallux valgus developing secondary to a tibial fracture. We report the case of acute post-traumatic hallux valgus due to compression of the medial plantar nerve in the tarsal tunnel. PMID- 20573501 TI - Enhancement of Candida parapsilosis catalyzing deracemization of (R,S)-1-phenyl 1,2-ethanediol to its (S)-enantiomer by a highly productive "two-in-one" resin based in situ product removal strategy. AB - In this study, a highly efficient process for Candida parapsilosis-catalyzed deracemization of racemic 1-phenyl-1,2-ethanediol (PED) was described, based on a resin-based in situ substrate feeding and product removal (ISSFPR) methodology. The resin H103 was selected and used to keep the combined concentration of (R) PED and (S)-PED at about 15g/l in aqueous phase. In the presence of 143g/l H103 resin, 50g/l of racemic substrate was converted to (S)-PED with 99.3% enantiomeric excess (ee) in 92% yield, while the initial reaction could afford an ee>99% only when the substrate concentration was 15g/l or lower. To our knowledge, this was the first report on the application of a resin-based ISSFPR technique for enhancing the efficiency of microbial stereoinversion. PMID- 20573502 TI - Effect of glycidyl methacrylate (GMA) on the thermal, mechanical and morphological property of biodegradable PLA/PBAT blend and its nanocomposites. AB - Poly(lactic acid) (PLA)/Polybutylene adipate co-terephthalate (PBAT) blend and its nanocomposites were prepared using melt blending technique. Glycidyl methacrylate (GMA) has been used as a reactive compatibilizer to improve the interface between PLA and PBAT. Mechanical studies indicated an increase in impact strength and tensile modulus of PLA matrix with the increase in PBAT loading. PLA/PBAT blend prepared at ratio of 75:25 exhibited optimum impact strength. Further, incorporation of GMA to the tune of 5wt.% and nanoclay shows an increase of impact strength. Morphological interpretations through SEM reveals improved interfacial adhesion between the PLA/PBAT blend in presence of GMA and nanoclay. XRD studies indicated an increase in d-spacing in PLA/PBAT/C20A blend nanocomposite thus revealing intercalated morphology. DSC and TGA thermograms also showed improved thermal properties as compared with virgin PLA. DMA tests revealed an increase in damping factor, confirming strong influence between PLA/PBAT blend in presence of GMA and nanoclay. PMID- 20573503 TI - Characterization and biotechnological potential of petroleum-degrading bacteria isolated from oil-contaminated soils. AB - A collection of 38 bacteria was obtained by enrichment cultivation from oil contaminated soils of an oil field in Daqing, China. Twenty-two strains could utilize diesel oil as the sole source of carbon and energy, and 11 strains could degrade the total petroleum hydrocarbons (TPHs) of diesel oil by more than 70% in 7d. Phylogenetically, 19 of the bacteria related to Bacillus species. About 87.5% TPHs of crude oil were degraded by a consortium of seven strains. Denaturing gradient gel electrophoresis analysis suggested that five of the strains persisted throughout the degradation process. The collection of isolated bacteria might be a useful resource for bioremediation of oil-contaminated soils and biotreatment of oil wastewater. PMID- 20573504 TI - Modelling biodegradation of nonylphenol ethoxylate in acclimated and non acclimated microbial cultures. AB - The biodegradation and inhibition kinetics of a commercial nonylphenol ethoxylate formulation were modelled for an activated sludge system fed with a synthetic substrate and nonylphenol ethoxylate mixture. Kinetic and stoichiometric coefficients of the proposed activated sludge model were obtained by employing on line respirometry. Experimental as well as model results confirmed that nonylphenol ethoxylate exhibited non-competitive inhibition on the hydrolysis process with a coefficient of 150mg/L on the basis of COD and negatively influenced biomass growth through a competitive inhibition mechanism with a coefficient of 500mg/L on the basis of COD, when the biomass was not acclimated. Upon acclimation of the activated sludge system, the inhibition concentration for non-competitive inhibition on hydrolysis was increased to 5000mg/L, practically showing no inhibition, and the coefficient of competitive inhibition increased to 450mg/L, corresponding to a significant decrease in the inhibitory effects of NPEO on growth. PMID- 20573505 TI - Synthesis of polyhalo acridones as pH-sensitive fluorescence probes. AB - Polyhalo isophthalonitriles were reacted with substituted anilines and subsequently cyclocondensed in the presence of sulfuric acid to give polyhalo acridones. These polyhalo acridones were proven to be useful as pH-sensitive fluorescent probes for a wide range of acidic and basic conditions. PMID- 20573506 TI - A specific and direct comparison of the trifluoromethyl and pentafluoro sulfanyl groups on the selective dopamine D(3) antagonist 3-(3-{[4-methyl-5-(4-methyl-1,3 oxazol-5-yl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-phenyl-3 azabicyclo[3.1.0]hexane template. AB - A direct and specific comparison of a trifluoromethyl group with the corresponding pentafluorosulfanyl group is made in terms of primary affinity and pharmacokinetic properties. PMID- 20573507 TI - Synthesis and evaluation of novel antifungal agents-quinoline and pyridine amide derivatives. AB - Quinoline amide, azaindole amide and pyridine amides were synthesized and tested for in vitro antifungal activity against fungi. These synthesized amides have potent antifungal activity against Candida albicans and Aspergillus fumigatus. Our results suggest that hetero ring amides may be potent antifungal agents that operate by inhibiting the function of Gwt1 protein in the GPI biosynthetic pathway. PMID- 20573508 TI - Aryl sulfonamides containing tetralin allylic amines as potent and selective bradykinin B1 receptor antagonists. AB - The bradykinin B1 receptor has been shown to mediate pain response and is rapidly induced upon injury. Blocking this receptor may provide a promising treatment for inflammation and pain. We previously reported tetralin benzyl amines as potent B1 antagonists. Here we describe the synthesis and SAR of B1 receptor antagonists with homobenzylic amines. The SAR of different linkers led to the discovery of tetralin allylic amines as potent and selective B1 receptor antagonists (hB1 IC(50)=1.3 nM for compound 16). Some of these compounds showed modest oral bioavailability in rats. PMID- 20573509 TI - 3-Cyano-6-(5-methyl-3-pyrazoloamino)pyridines: selective Aurora A kinase inhibitors. AB - A new class of Aurora A kinase inhibitor was created by transforming 4-(5-methyl 3-pyrazoloamino)pyrimidine moiety of VX-680 to 3-cyano-6-(5-methyl 3pyrazoloamino)pyridine. Compound 6 exhibited a potent Aurora A kinase inhibitory activity, excellent selectivity to Aurora B kinase and other 60 kinases, good cell permeability and good PK profile. Therefore compound 6 was effective in antitumor mice model at a dose of 30 mg/kg po qd without decrease of body weight. PMID- 20573510 TI - Energy expenditure of stroke patients during postural control tasks. AB - Two common impairments in patients after stroke are loss of balance control and fatigue. We propose that both could be inter-related. The purpose of this study was to investigate the metabolic energy demand for balance control in patients after stroke during upright standing. Ten stroke patients and 12 able-bodied controls performed four 5-min upright standing tasks on a force plate; unperturbed (SU), blindfolded (SUB), on foam surface (SUF) and with feet parallel against each other (SUP). Metabolic energy expenditure, posturography measures and muscle activity (EMG) of lower leg muscles were measured. Patients required on average 125% (33Jkg(-1)s(-1)) more metabolic energy for upright standing under the various conditions than controls. In addition, balance manipulation significantly (p<0.05) affected energy expenditure (21% higher in SUB, 52% in SUF, 40% in SUP compared to SU). Although the increase in energy expenditure was on average twice as high in patients than controls no significant group by condition interaction effect was found. Overall correlations between posturography measures, EMG and energy expenditure (r=0.33-0.60) were significant (p<0.001). We conclude that impaired balance control puts an extra demand on the energy expenditure during motor activities in stroke patients. This should be considered when prescribing interventions aimed at reducing physiological strain. PMID- 20573511 TI - Sagittal and frontal plane joint mechanics throughout the stance phase of walking in adolescents who are obese. AB - The incidence of obesity has increased dramatically in children and adolescents, and with this comes health risks typically associated with adult obesity. Among those health consequences are musculoskeletal damage and pain. Previous studies have demonstrated inconsistent effects of increased body mass on movement patterns in adults and children who are obese. The purpose of this study was to investigate frontal and sagittal plane mechanics during walking in adolescents who were obese. Adolescents (12-17 years) who were obese were recruited from a weight management program, and healthy weight peers (matched for age, race and gender) were recruited from the community. Three-dimensional motion analysis of the lower extremities was performed during walking. Analysis of kinematic and kinetic data from 36 adolescents who were obese and healthy weight revealed significant differences in mechanics at all lower extremity joints in both sagittal and frontal planes. Subjects who were obese seemed to use movement strategies that minimized joint moments, especially at the hip and knee during walking. The lower extremity mechanics during walking in the subjects who were obese raise concerns about maintenance of structural integrity of the lower extremity joints over time, given the repeated high stresses across the joints even with walking. Neither the long term consequences of these atypical movement patterns, nor the ability to alter these patterns through therapeutic activities or weight loss has been investigated in adolescents who are obese. PMID- 20573512 TI - Gillette Gait Index in adults. AB - Gillette Gait Index (GGI) is a very useful tool to assess gait abnormalities. However, it seems that it has only been validated in children with cerebral palsy. Nevertheless, the parameters used to compute GGI are not specific to children population. Our aim is to demonstrate that GGI could also be used to evaluate adults gait abnormalities. 44 adults (25 healthy and 19 pathological) participated to this study. Pathological subjects had a diagnosis of central nervous system pathology (6 with spinal cord injury and 13 with brain injury). We first, compared the kinematic parameter values of our healthy adult group to healthy children group in previous studies. It appears that those parameters' variability is a bit lower in adults, which makes the GGI more sensitive. Moreover, the GGI in adults is too much dependent on one parameter among the 16 proposed by Schutte et al. (2000), the "Time of Peak Flexion". Finally, the Edinburgh Visual Gait Score (EVGS) is correlated to GGI in children. To emphasize the relevance of GGI in adults, we have evaluated the correlation between EVGS and GGI in our pathological group. Those two parameters are indeed highly correlated. All these results allow us to conclude that the GGI computed with the 15 remaining parameters is a useful tool to assess gait abnormalities in adults. PMID- 20573513 TI - What's in a name? The semantics of quorum sensing. AB - The expression of many bacterial phenotypes is regulated according to the concentration of chemical cues that they or other bacteria produce, a process often termed quorum sensing (QS). Many aspects of the environment can affect cue concentration. Thus these molecules might be indirect proxies for any one or combination of environmental factors. Recent research suggests that the adaptive significance of QS varies depending on its evolutionary and ecological context. Consequently, some researchers have proposed new terms, each emphasizing different adaptive functions, for the QS process. However, these new terms generate potential for a semantic quagmire and perpetuate the questionable notion that we can identify a single, dominant environmental feature to which the microbes respond. In fact, the ecological context of QS regulation, like the process itself, is complex and impacted by multiple aspects of natural environments. PMID- 20573515 TI - Development of landmine detection system based on the measurement of radiation from landmines. AB - For the detection of landmines, a new gamma-ray detector system, a neutron source, and control and measurement devices were developed. A prototype system has newly been developed by combining these devices. The usefulness of capture gamma-ray and backscattering neutron methods is examined with real explosives in several conditions and the performance of the prototype landmine detection system is demonstrated experimentally in this study. The combination of the methods is confirmed to be sufficiently effective for application to actual landmine detection. PMID- 20573514 TI - Identification of novel bacterial histidine biosynthesis inhibitors using docking, ensemble rescoring, and whole-cell assays. AB - The rapid spread on multidrug-resistant strains of Staphylococcus aureus requires not just novel treatment options, but the development of faster methods for the identification of new hits for drug development. The exponentially increasing speed of computational methods makes a more extensive use in the early stages of drug discovery attractive if sufficient accuracy can be achieved. Computational target identification using systems-level methods suggested the histidine biosynthesis pathway as an attractive target against S. aureus. Potential inhibitors for the pathway were identified through docking, followed by ensemble rescoring, that is sufficiently accurate to justify immediate testing of the identified compounds by whole-cell assays, avoiding the need for time-consuming and often difficult intermediary enzyme assays. This novel strategy is demonstrated for three key enzymes of the S. aureus histidine biosynthesis pathway, which is predicted to be essential for bacterial biomass productions. Virtual screening of a library of approximately 10(6) compounds identified 49 potential inhibitors of three enzymes of this pathway. Eighteen representative compounds were directly tested on three S. aureus- and two Escherichia coli strains in standard disk inhibition assays. Thirteen compounds are inhibitors of some or all of the S. aureus strains, while 14 compounds weakly inhibit growth in one or both E. coli strains. The high hit rate obtained from a fast virtual screen demonstrates the applicability of this novel strategy to the histidine biosynthesis pathway. PMID- 20573516 TI - UV-A enhanced growth and UV-B induced positive effects in the recovery of photochemical yield in Gracilaria lemaneiformis (Rhodophyta). AB - The effects of solar UV radiation (280-400 nm) on growth, quantum yield and pigmentation in Gracilaria lemaneiformis were investigated when the thalli were cultured under solar radiation with or without UV for a period of 15 days. Presence of UV-A (315-400 nm) enhanced the relative growth rate, while UV-B (218 315 nm) inhibited it. The positive effect of UV-A and negative effect of UV-B counteracted to result in an insignificant impact of UVR on growth. During the noon period, both UV-A and UV-B resulted in the decrease of maximum quantum yield (Fv/Fm), but UV-B aided in the recovery of the yield in the late afternoon, reflecting that UV-B might be used as a signal in photorepair processes. UV induced the accumulation of UV-absorbing compounds (UVAC) to defend against the harmful UVR. However, the accumulation of UVAC took a much longer time compared to that previously reported, which was probably due to the lower levels of solar radiation and water temperature in the early spring period. Unknown UV-absorbing compounds (UVAC), which peaked at 265 nm, probably the precursor of MAAs (UVAC(325)), accumulated under moderate levels of solar radiation and were transformed to MAAs under higher solar radiation. PMID- 20573517 TI - Interaction between a potent corticosteroid drug - dexamethasone with bovine serum albumin and human serum albumin: a fluorescence quenching and fourier transformation infrared spectroscopy study. AB - This study was designed to examine the interaction of dexamethasone (DEX) with bovine serum albumin (BSA) and human serum albumin (HSA) under physiological conditions with drug concentrations in the range of 2.5-20 microM and BSA/HSA was fixed at 5.0 microM. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of serum albumin by dexamethasone is static quenching mechanism. The binding sites number, n and binding constant, K were obtained at various temperatures. The distance r between dexamethasone and the protein was evaluated according to the theory of Foster energy transfer. The result of fluorescence spectra UV-vis absorption spectra and FT-IR spectra showed that the conformation of bovine serum albumin and human serum albumin has been changed in the presence of dexamethasone. The thermodynamic parameters, free energy change (DeltaG(0)), enthalpy change (DeltaH(0)) and entropy change (DeltaS(0)) for BSA-DEX and HSA-DEX were calculated according to van't Hoff equation and discussed. PMID- 20573518 TI - Host-pathogen interactions in the development of metabolic disturbances and atherosclerosis in HIV infection: the role of CCL2 genetic variants. AB - BACKGROUND: Circulating CCL2 concentration has been implicated in promoting atherosclerosis in patients infected with HIV. We evaluated whether CCL2 gene variants are associated with metabolic disturbances and plasma CCL2 levels in HIV infected patients. METHODS AND RESULTS: CCL2 genotypes and estimated haplotypes, plasma CCL2 levels and indicators of metabolic status in HIV-infected patients were compared with a representative group of the general population. We also performed a carotid/femoral artery ultrasonography to detect sub-clinical atherosclerosis in these patients. Six haplotypes were estimated in more than the 5% of individuals, and accounted for more than 98% of the population. In HIV infected patients, carriers of H1, H2 and H5 haplotypes had higher CCL2 concentration than carriers of H3, H4 and H6 haplotypes. However, only carriers of H1 and H5 haplotypes presented higher insulin resistance as well as higher proportion of patients affected with sub-clinical. Conversely, carriers of H2 haplotype, which also showed high plasma CCL2 concentration, were associated with less deleterious metabolic disturbances. CONCLUSIONS: Our data are consistent with the hypothesis that the genetic background of the host is involved in CCL2 production and that this chemokine is implicated in promoting metabolic disturbances and sub-clinical atherosclerosis in HIV-infected patients. PMID- 20573519 TI - Avulsion of a bronchial blocker cuff in the trachea when using a Parker Flex-Tip endotracheal tube. PMID- 20573520 TI - Low cardiac output after surgical correction of tetralogy of Fallot: hidden culprits. PMID- 20573521 TI - Left atrial mass during a minimally invasive thoracic mitral valve replacement. PMID- 20573523 TI - Improvement in bedtime plasma glucose level serves as a predictor of long-term blood glucose control in patients with Type 2 diabetes: a study with monotherapy of 50/50 premixed insulin analogue three times daily injection. AB - AIM: To examine which timing of blood glucose level is more important to achieve adequate blood glucose control with insulin lispro mixture-50 (Mix 50) three times daily (TID) monotherapy. METHODS: The study enrolled 35 Type 2 diabetic patients. Blood glucose levels before each meal and at bedtime were measured 2 weeks after the start of the study and were analyzed in relation to improvement in hemoglobin A1c (HbA1c) at 6-8 weeks and 6 months. RESULTS: HbA1c improved significantly (10.1+/-1.6 % at baseline, 7.8+/-1.1 % at 6-8 weeks and 6.8+/-1.1 % at 6 months). Only the blood glucose level measured at bedtime correlated with improvement in HbA1c at 6-8 weeks. For the insulin-naive patients, only bedtime plasma glucose level also had a significant correlation with improvement in HbA1c at 6 months. CONCLUSIONS: Bedtime plasma glucose level can serve as a predictor of the outcome of long-term blood glucose control during Mix 50 TID monotherapy and that bedtime plasma glucose level needs to be reduced sufficiently to achieve adequate blood glucose control. PMID- 20573526 TI - An update of the role of endovascular repair in blunt carotid artery trauma. AB - Blunt carotid injury (BCAI) is an increasingly recognised entity in trauma patients. Without a prompt diagnosis and a proper treatment, they can result in devastating consequences with cerebral ischaemia rate of 40-80% and mortality rate of 25-60%. Several applied screening protocols and continuously improving diagnostic modalities have been developed to identify patients with BCAI. The appropriate treatment of BCAI still remains controversial and strictly individualised. Besides anti-thrombotic/anticoagulation therapy and surgical intervention, continuously evolving endovascular techniques emerge as an additional treatment option for patients with BCAI. We provide an update on blunt carotid trauma, emphasising the role of endovascular approaches. PMID- 20573524 TI - A computational study of the magnitude and direction of migration forces in patient-specific abdominal aortic aneurysm stent-grafts. AB - OBJECTIVES: Endovascular aneurysm repair for abdominal aortic aneurysm (AAA) is now a widely adopted treatment. Several complications remain to be fully resolved and perhaps the most significant of these is graft migration. Haemodynamic drag forces are believed to be partly responsible for migration of the device. The objective of this work was to investigate the drag forces in patient-specific AAA stent-grafts. METHODS: CT scan data was obtained from 10 post-operative AAA patients treated with stent-grafts. 3D models of the aneurysm, intraluminal thrombus and stent-graft were created. The drag forces were determined by fluid structure interaction simulations. A worst case scenario was investigated by altering the aortic waveforms. RESULTS: The median resultant drag force was 5.46 N (range: 2.53-10.84). An increase in proximal neck angulation resulted in an increase in the resultant drag force (p = 0.009). The primary force vector was found to act in an anterior caudal direction for most patients. The worst case scenario simulation resulted in a greatest drag force of 16 N. CONCLUSIONS: Numerical methods can be used to determine patient-specific drag forces which may help determine the likelihood of stent-graft migration. Anterior-posterior neck angulation appears to be the greatest determinant of drag force magnitude. Graft dislodgement may occur anteriorally as well as caudally. PMID- 20573527 TI - Cigarette smoke inhalation modulates gene expression in sites of bone healing: a study in rats. AB - OBJECTIVE: The aim of this study was to assess the effect of cigarette smoke inhalation (CSI) on gene expression in alveolar bone healing sites. STUDY DESIGN: Wistar rats were randomly assigned to the groups: control [animals not exposed to CSI (n = 20)] and test [animals exposed to CSI, starting 3 days before teeth extraction and maintained until killing them (n = 20)]. First mandibular molars were bilaterally extracted, and the expression of alkaline phosphatase, bone morphogenetic protein (BMP) 2 and 7, receptor activator of nuclear factor kappaB ligand, osteoprotegerin, and d2 isoform of vacuolar adenosine triphosphatase V(0) domain were assessed by quantitative polymerase chain reaction in the newly formed tissue in the sockets. RESULTS: Overall, data analysis demonstrated that CSI significantly affected the expression pattern of all of the studied genes except BMP-7. CONCLUSION: The expression of key genes for bone healing may be affected by CSI in tooth extraction sites. PMID- 20573528 TI - An in vitro evaluation of apicoectomies and retropreparations using different methods. AB - OBJECTIVES: The aim of this study was to evaluate: 1) the apical root surface, gutta-percha interface, and preparation time of root-end resections made with burs, ultrasound, or laser; and 2) the thickness of surrounding dentin after laser or ultrasonic root-end cavity preparation. STUDY DESIGN: 1) Thirty root filled teeth were resected as follows: Zekrya bur in group I, Chemical Vapor Deposition (CVD) ultrasonic tip (9.5107-8) in group II, and ErCr:YSGG (Waterlase) in group III. The preparation time was recorded. Replicas of the resected root ends were examined under a scanning electron microscope (SEM). 2) Thirty root filled teeth were submitted to apicectomies and root-end cavities were prepared by using: CVD (6.1107-6) ultrasonic retrotips (group IV), EMS (DT-060) ultrasonic retrotips (group V), and ErCr:YSGG laser tips (group VI). Replicas of the root apices were examined under a SEM. RESULTS: There were no fissures or fractures on root-end surfaces. The bur produced the smoothest surface (P < .05). Group I had the lowest preparation time (P < .05). The best adaptation between the filling and the root canals walls was observed in group III, but it was not significantly different from group II (P < .05). No resected root-ends had cracks after preparation. Group VI showed the least minimum dentin thickness (P < .05). CONCLUSIONS: The 3 methods evaluated did not cause any injury to the root-end surface, but they harmed the apical adaptation. Laser tips removed more dentin than ultrasonic retrotips and should be used with care to avoid overpreparation. PMID- 20573529 TI - Long-term success and survival rates of autogenously transplanted canines. AB - OBJECTIVES: The objectives of this study were to determine the long-term survival and success rates of autotransplanted canines and to investigate the influence of various parameters on the long-term success rate. STUDY DESIGN: Fifty-nine patients (73 transplanted canines) volunteered to participate in this study. The mean follow-up time was 11 years. Different parameters that could influence the outcome of transplantation were examined in the patient files. Each transplanted canine was clinically and radiologically evaluated. Logistic regression analyses were performed. RESULTS: The survival rate was 75.3%, because 18 transplanted teeth were lost before examination. The success rate for all transplanted teeth was 57.5%, because 42 transplanted teeth were evaluated as clinically successful. The most significant parameter in determining the success rate of autotransplantation was age at transplantation (P = .0429). CONCLUSION: Autotransplantation of impacted canines may have a successful outcome 11 years after transplantation. The success rate increases when performing the transplantation at a younger age. PMID- 20573530 TI - Evaluation of smear layer removal after use of a canal brush: an SEM study. AB - OBJECTIVE: The objective of this study was to evaluate smear layer removal after using the new CanalBrush (Coltene/Whaledent GmbH+Co. KG, Germany). STUDY DESIGN: Twenty extracted maxillary anterior teeth were randomly divided into 2 equal groups. The canals of the teeth in each group were instrumented with ProTaper Universal rotary files (Dentsply Maillefer, Switzerland). Following each file use, the root canals in both groups were irrigated with 5.25% NaOCl and 15% EDTA. At the end of instrumentation, the canals in group 2 were flushed with 15% EDTA, then a CanalBrush was used for 30 seconds, and a final irrigation was conducted with 5.25% NaOCl. All teeth were processed for scanning electron microscopy (SEM), and the removal of the smear layer was examined in the apical, middle, and coronal thirds. Analyses of SEM images were performed by 2 independent evaluators in a blinded manner and using a 4-point scoring system. RESULTS: The middle and apical thirds of the root canals in group 2 showed lower average scores than those in group 1, but the difference was not statistically significant. There was no significant difference in the coronal score between the groups (P > .05). CONCLUSIONS: Irrigating with brushing tended to produce cleaner canal walls, but irrigating brushing was not significantly better than irrigation alone in removing the smear layer on the canal walls. PMID- 20573531 TI - An ex vivo comparison of root canal length determination by three electronic apex locators at positions short of the apical foramen. AB - OBJECTIVE: The aim of this study was to evaluate the precision of working length determination of 3 electronic apex locators (EALs): Root ZX, RomiApex D-30, and Ipex at 0.0 mm, at the apical foramen (AF), and at 1.0 mm short of the AF. METHODOLOGY: Thirty-eight mandibular premolars had their real lengths previously determined. Electronic measurements were determined at 1.0 mm, followed by measurements at 0.0 mm, performed in triplicate. RESULTS: Precision of devices at 1.0 mm and 0.0 mm were: 94.7% and 97.4%, respectively (Root ZX); 78.9% and 97.4% (RomiApex D-30); and 76.3% and 97.4% (Ipex). Although no statistical differences were observed between the EALs at 0.0, at 1.0 mm Root ZX performed significantly better than the others. CONCLUSION: The EALs had acceptable precision when measuring the working length at the AF. However, when used at levels short of the AF, only Root ZX did not suffer a significant negative effect on precision. PMID- 20573532 TI - Homogeneity of root canal fillings performed by undergraduate students with warm vertical and cold lateral techniques. AB - OBJECTIVES: The aim of this study was to determine radiographic and microscopic appearances of root canal fillings performed by undergraduate students using vertical and lateral compaction techniques. STUDY DESIGN: Thirty dental students were instructed how to fill curved simulated canals with gutta-percha and sealer using lateral and vertical compaction. Digital radiographs were taken in buccolingual and mesio-distal projections; radiographs were evaluated for homogeneity and root canal wall contact. Plastic blocks with simulated canals were sectioned and cross sections were assessed under a light microscope for voids. Probabilities were expressed as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Radiographs showed that the chances of obtaining a homogeneous root canal filling by using a vertical compaction technique were 3 times higher in the coronal canal third (OR 3.2; CI: 1.9, 5.3), the same in the middle third, and 2 times higher in the apical third (CI: 1.1, 2.4) than when using lateral compaction. Microscopic evaluation of the same canals revealed that the chances of obtaining a homogeneous root canal filling by vertical compaction were 3 times higher in the coronal canal third (CI: 1.6, 5.8), almost 3 times higher in the middle canal third (CI: 1.6, 4.7), and about 10 times higher in the apical canal third (OR 9.8; CI: 2.2, 43.4) than by lateral compaction. The chances of transporting filling material beyond the apex were almost 5 times higher (OR 4.6; CI: 2.8, 7.6) when using vertical rather than lateral compaction. CONCLUSION: Inexperienced students obtained more homogeneous root canal fillings with the vertical compaction method; however, the probability of overextruding filling material with this method was high. PMID- 20573533 TI - An experimental study of use of absorbable plate in combination with self-setting alpha-tricalcium phosphate for orthognathic surgery. AB - OBJECTIVE: The purpose of this study was to histologically and immunohistochemically evaluate bone formation using both self-setting alpha tricalcium phosphate (alpha-TCP; Biopex) and absorbable plate (Super Fixsorb-MX) in rabbit cranium bone. STUDY DESIGN: Twelve adult male Japanese white rabbits (12-16 wk, 2.5-3.0 kg) were used. The surgical defects were made in the nasal bone of a rabbit, and Biopex was implanted in the left side and no material in the right side. Two-hole absorbable plate and 2 screws (Super Fixsorb-MX) were fixed across the defect in each side. The rabbits were killed at 1, 4, 12, and 24 weeks after surgery, and formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with hematoxylin and eosin. For immunohistochemical analysis, the specimens were treated with bone morphogenetic protein 2 (BMP-2) antibodies. Finally, these were evaluated microscopically. RESULTS: New bone formation was observed in the region of absorbable plate and nasal membrane after >4 weeks. The area of new bone with Biopex was significantly larger than that of the control side after 1, 4, and 12 weeks (P < .05). The number of BMP-2-stained cells in the experimental side was significantly larger than in the control side after 4 and 12 weeks (P < .05). CONCLUSION: This study suggests that the use of absorbable plate (Super Fixsorb-MX) in combination with Biopex could be useful and that both of Super Fixsorb-MX and Biopex could provide adequate bone regeneration. PMID- 20573534 TI - Odontogenic dysplasia in the molar teeth of Steppe lemmings (Lagurus lagurus). AB - In a colony of Steppe lemmings (Lagurus lagurus), of the rodent sub-family Arvicolinae, 8.6% of animals exhibited dysplastic growth of the molar teeth. Clinical findings included nodular swellings of the mandible, hypersalivation, malocclusion and emaciation. To investigate the underlying cause, two control and 10 affected animals, aged between 6 and 18 months, were examined using radiography and computed tomography and at post mortem examination. Bilaterally symmetrical masses were identified in the molar regions of the left and right mandible and maxillae. Histologically, the masses were characterised by dysplastic odontogenic epithelium, dentin, cementum, enamel and dental pulp formation that resembled odontogenic dysplasia. This tumour-like proliferative lesion has been reported in the continuously-growing incisor teeth of ageing rodents and lagomorphs but this is the first description of the clinico pathological features of such odontogenic dysplasia of the molar teeth of Steppe lemmings. PMID- 20573535 TI - Effect of resonance frequency, power input, and saturation gas type on the oxidation efficiency of an ultrasound horn. AB - The sonochemical oxidation efficiency (eta(ox)) of a commercial titanium alloy ultrasound horn has been measured using potassium iodide as a dosimeter at its main resonance frequency (20 kHz) and two higher resonance frequencies (41 and 62 kHz). Narrow power and frequency ranges have been chosen to minimise secondary effects such as changing bubble stability, and time available for radical diffusion from the bubble to the liquid. The oxidation efficiency, eta(ox), is proportional to the frequency and to the power transmitted to the liquid (275 mL) in the applied power range (1-6 W) under argon. Luminol radical visualisation measurements show that the radical generation rate increases and a redistribution of radical producing zones is achieved at increasing frequency. Argon, helium, air, nitrogen, oxygen, and carbon dioxide have been used as saturation gases in potassium iodide oxidation experiments. The highest eta(ox) has been observed at 5 W under air at 62 kHz. The presence of carbon dioxide in air gives enhanced nucleation at 41 and 62 kHz and has a strong influence on eta(ox). This is supported by the luminol images, the measured dependence of eta(ox) on input power, and bubble images recorded under carbon dioxide. The results give insight into the interplay between saturation gas and frequency, nucleation, and their effect on eta(ox). PMID- 20573536 TI - Acoustical analysis of mechanical heart valve sounds for early detection of malfunction. AB - Mechanical heart valves carry the disadvantage of lifelong antithrombotic therapy, due to the high risk of thrombus formation on the valve surface. Current diagnostic methods are incapable of detecting thrombus formation in an early stage. This article investigates a new diagnostic method, based on the analysis of the acoustic signal produced by the valve. This method should be capable of early detection of malfunction, thus permitting targeted medication and reducing valve-related complications and mortality. A measurement setup assuring optimal signal quality was developed, and a signal analysis program was implemented and validated on an in vitro mock circulatory loop. Next, four sheep were implanted with a bileaflet mechanical valve. The signals of their valves developing thrombosis were assessed on a weekly basis before explantation. Three sheep were sacrificed shortly after detection of malfunction according to the newly developed method. In each case, thrombus or membrane formation was detected on the leaflets upon explantation. In one sheep, no malfunction was found in the analysis, which was also confirmed by the condition of the valve upon explantation. These preliminary results indicate that acoustical analysis of mechanical heart valves permits early detection of valvular malfunction. Further research with more in vitro and animal testing is required to statistically validate these findings. PMID- 20573537 TI - Diffusion tensor imaging of the corpus callosum differentiates corticobasal syndrome from Parkinson's disease. AB - Differential diagnosis between patients with Corticobasal syndrome (CBS) and Parkinson's disease (PD) may be confusing, particularly in early disease stages. However, in contrast to PD, CBS shows a widespread cortical atrophy that suggests an involvement of the corpus callosum (CC). To test this hypothesis, we used diffusion tensor imaging (DTI) with a 1.5T scanner to compare 14 CBS patients, 14 PD patients, and an age-matched control group. The mean diffusivity (MD) and fractional anisotropy (FA) were determined in the whole CC and in five subdivisions. Group comparisons were performed using the Mann-Whitney U-test. We found a significantly increased MD and decreased FA in CBS patients compared to PD, particularly in the posterior truncus. No differences were found between PD patients and controls. A receiver-operating characteristics (ROC) analysis shows that the MD is particularly useful for discriminating between the two neurodegenerative diseases. Our data suggest that abnormal CC diffusivity in CBS reflects an atrophy and degraded transcallosal connectivity, making the CC a potential target to differentiate CBS from PD patients. PMID- 20573538 TI - Comparing and combining algorithms for computer-aided detection of pulmonary nodules in computed tomography scans: The ANODE09 study. AB - Numerous publications and commercial systems are available that deal with automatic detection of pulmonary nodules in thoracic computed tomography scans, but a comparative study where many systems are applied to the same data set has not yet been performed. This paper introduces ANODE09 ( http://anode09.isi.uu.nl), a database of 55 scans from a lung cancer screening program and a web-based framework for objective evaluation of nodule detection algorithms. Any team can upload results to facilitate benchmarking. The performance of six algorithms for which results are available are compared; five from academic groups and one commercially available system. A method to combine the output of multiple systems is proposed. Results show a substantial performance difference between algorithms, and demonstrate that combining the output of algorithms leads to marked performance improvements. PMID- 20573539 TI - Interventional 4D motion estimation and reconstruction of cardiac vasculature without motion periodicity assumption. AB - Anatomical and functional information of cardiac vasculature is a key component in the field of interventional cardiology. With the technology of C-arm CT it is possible to reconstruct static intraprocedural 3D images from angiographic projection data. Current approaches attempt to add the temporal dimension (4D). In the assumption of periodic heart motion, ECG-gating techniques can be used. However, arrhythmic heart signals and slight breathing motion are degrading image quality frequently. To overcome those problems, we present a reconstruction method based on a 4D time-continuous B-spline motion field. The temporal component of the motion field is parameterized by the acquisition time and does not assume a periodic heart motion. The analytic dynamic FDK-reconstruction formula is used directly for the motion estimation and image reconstruction. In a physical phantom experiment two vessels of size 3.1mm and 2.3mm were reconstructed using the proposed method and an algorithm with periodicity assumption. For a periodic motion both methods obtained an error of 0.1mm. For a non-periodic motion the proposed method was superior, obtaining an error of 0.3mm/0.2mm in comparison to 1.2mm/1.0mm for the algorithm with periodicity assumption. For a clinical test case of a left coronary artery it could be further shown that the method is capable to produce diameter measurements with an absolute error of 0.1mm compared to state-of-the-art measurement tools from orthogonal coronary angiography. Further, it is shown for three different clinical cases (left/right coronary artery, coronary sinus) that the proposed method is able to handle a large variability of vascular structures and motion patterns. The complete algorithm is hardware-accelerated using the GPU requiring a computation time of less than 3min for typical clinical scenarios. PMID- 20573540 TI - Approaches to cognitive modeling. PMID- 20573541 TI - Spectroscopic and physicochemical studies on organic crystal of brucine hydrogen maleate pentahydrate. AB - Salt of brucine hydrogen maleate pentahydrate was synthesized and grown as a single crystal by slow evaporation solution growth technique. The cell parameters of the grown crystal were calculated from powder XRD. The presence of the functional groups and the nature of the vibrations were identified in vibrational studies. The decomposition character of the title material was studied by recording TGA/DTA. The way of promotion of electron from ground state to higher energy state was premeditated by recording UV-VIS-NIR spectrum also the mechanical behaviour was deliberated in hardness measurement. PMID- 20573542 TI - Customized stimulation enhances performance of independent binary SSVEP-BCIs. AB - OBJECTIVE: Brain-computer interfaces based on steady-state visual evoked potentials (SSVEP-BCIs) achieve the highest performance, due to their multiclass nature, in paradigms in which different visual stimuli are shown. Studies of independent binary SSVEP-BCIs have been previously presented in which it was not necessary to gaze at the stimuli at the cost of performance. Despite that, the energy of the SSVEPs is largely affected by the temporal and spatial frequencies of the stimulus, there are no studies in the BCI literature about its combined impact on the final performance of SSVEP-BCIs. The objective of this study is to present an experiment that evaluates the best configuration of the visual stimulus for each subject, thus minimizing the decline in performance of independent binary SSVEP-BCIs. METHODS: The participants attended and ignored a single structured stimulus configured with a combination of spatial and temporal frequencies at a time. They were instructed to gaze at a central point during the whole experiment. The best combination of spatial and temporal frequencies achieved for each subject, in terms of signal-to-noise ratio (SNR), was subsequently determined. RESULTS: The SNR showed a significant dependency on the combination of frequencies, in such a way that only a reduced set of these combinations was applicable for obtaining an optimum SNR. The selection of an inappropriate stimulus configuration may cause a degradation of the information transmission rate (ITR) as it does the SNR. CONCLUSIONS: The appropriate selection of the optimal spatial and temporal frequencies determines the performance of independent binary SSVEP-BCIs. This fact is critical to enhance its low performance; hence, they should be adjusted independently for each subject. SIGNIFICANCE: Independent binary SSVEP-BCIs can be used in patients who are unable to control their gaze sufficiently. The correct selection of the spatial and temporal frequencies has a considerable benefit on their low ITR that must be taken into account. In order to find the most suitable frequencies, a test similar to the presented in this study should be performed beforehand for each SSVEP-BCI user. This regard is not documented in studies conducted in the BCI literature. PMID- 20573545 TI - Transcatheter aortic valve implantation complicated by acute structural valve failure requiring immediate valve in valve implantation. AB - The first percutaneous transcatheter aortic valve implantation (TAVI) was performed in 2002 by Alain Cribier with over 10,000 valve implants since. Despite this, as with all new technologies we remain on a learning curve and continue to encounter new challenges and complications. We report a case of acute structural valve failure treated successfully with a second valve in valve implantation of transcatheter aortic valve in a patient who had severe aortic stenosis (AS) complicated by a severely unfolded aorta. PMID- 20573544 TI - Ammonia accumulation in culture broth by the novel nitrogen-fixing bacterium, Lysobacter sp. E4. AB - This is the first report that Lysobacter fixes nitrogen under free-living conditions, as shown by its ability to grow on nitrogen-free medium and accumulate relatively high amounts of ammonia in the culture broth. Growth of the E4 Lysobacter strain, isolated in a screen for nitrogen-fixing and ammonia producing bacteria, resulted in higher ammonia accumulation (0.53 mM ammonium ion concentration) in media containing glucose rather than other tested carbon sources. The optimum glucose concentration was 0.30% at an initial medium pH of 7.0 and incubation temperature of 30 degrees C. From time-course experiments, when the glucose in the culture was exhausted, ammonia began to be accumulated, and maximum ammonia accumulation (~1.60 mM) was reached after 8 days of incubation. Ammonia accumulation by this strain required molybdenum, manganese, and iron. PMID- 20573543 TI - Subdural electrodes. AB - Subdural electrodes are frequently used to aid in the neurophysiological assessment of patients with intractable seizures. We review the indications for these, their uses for localizing epileptogenic regions and for localizing cortical regions supporting movement, sensation, and language. PMID- 20573546 TI - Fistula from aneurysmal saphenous vein graft to right atrium treated with covered stents. AB - Rarely aneurysmal dilatation of saphenous vein grafts following coronary artery bypass surgery may be complicated by fistulae which communicate with cardiac chambers. We describe our attempt to close a fistula which entered the right atrium by deploying covered stents within the graft. PMID- 20573548 TI - Regulation of trophoblast migration and survival by a novel neural regeneration peptide. AB - Although placental trophoblast migration is tightly controlled in an autocrine/paracrine manner, the nature of chemoattractive factors facilitating and directing this biological activity remains largely elusive. Neural regeneration peptides (NRP), a recently discovered peptide family, stimulate neuronal migration, differentiation and survival of post-natal neurons within the murine central nervous system. Based on the neural-repair related activities of these peptides and parallels between neuronal and placental cell behaviour patterns, this study postulated that they play a role in placental development, in particular trophoblast migration and survival and investigated the role of a newly discovered NRP motif (NNZ-4920), which exhibits about 70% homology to the mouse NRP motif sequence and is homologous to a 13-mer fragment within the N terminus of human CAPS2, in trophoblast migration and survival regulation. NNZ 4920 significantly enhanced trophoblast migration by 51% (P<0.01) compared with controls and protected against stress induced by serum withdrawal and tumour necrosis factor-alpha/interferon-gamma treatment, at femtomolar concentrations, with efficacy similar to epidermal growth factor. CAPS2 expression was detected in purified term trophoblast and decidual cells. In conclusion, the placenta may be a source of NRP-related gene expression. Its encoded peptide products exert biological effects on term trophoblast migration and survival in vitro. PMID- 20573549 TI - The male partners' experiences of the intimate relationships after a first myocardial infarction. AB - BACKGROUND: Stress in the intimate relationship is found to worsen the prognosis in women suffering from myocardial infarction (MI). Little is known about how male spouses experience the intimate relationship. AIM: This study aimed to explore and describe the experience of men's intimate relationships in connection to and after their female partner's first MI. METHODS: An explorative and qualitative design was used. Interviews were conducted with 16 men having a partner who the year before had suffered a first MI. The data were analysed with qualitative content analysis. RESULTS: Three themes emerged: masculine image challenged; life takes another direction; and life remains unchanged. The men were forced to deal with an altered image of themselves as men, and as sexual beings. They were hesitant to approach their spouse in the same way as before the MI because they viewed her to be more fragile. The event also caused them to consider their own lifestyle, changing towards healthier dietary and exercise habits. CONCLUSIONS: After their spouse's MI, men experienced a challenge to their masculine image. They viewed their spouse as being more fragile, which led the men to be gentler in sexual intimacy and more hesitant to invite sexual activity. This knowledge about how male spouses experience the intimate relationship could be helpful for health personnel in hospitals and primary care when they interact with couples where the woman suffers from cardiac disease or other chronic disorders. PMID- 20573547 TI - Immunotherapy for allergies and asthma: present and future. AB - Allergen immunotherapy (IT) is a proven approach for treating allergic rhinitis and allergic asthma that has been practiced since 1911 and has undergone significant development in the past two decades. As currently practiced, IT involves subcutaneous or sublingual administration of allergens, both methods of which have been extensively investigated. In addition to allergen IT, a number of additional nonspecific IT approaches are being used or are in phase II/phase III clinical trials, which may be available in clinics within the next one to three years. Such therapies include anti-IgE antibodies and the soluble IL-4 receptor. Other experimental IT approaches are at the preclinical research stage and may proceed to clinical trials and the clinic within the next five to ten years. This review discusses the pros and cons of recent developments in both currently practiced and experimental IT approaches. PMID- 20573550 TI - Low-frequency oscillations in R-R interval and blood pressure across the continuum of cardiovascular risk. AB - The purpose of this study was to assess the power and the frequency of low frequency (LF; 0.04-<0.15 Hz) oscillations in systolic blood pressure (SBP) and R R interval (RRi) across the continuum of risk of cardiovascular disease, including age. A potential confound in such determinations is low spontaneous breathing frequency in some individuals. We measured beat-to-beat SBP, RRi and respiration in healthy YOUNG (33+/-3 years) and OLDER subjects (62+/-5 years) and older patients with hypertension (HT, 61+/-5 years), coronary artery disease without (CAD, 62+/-5 years) and with type 2 diabetes (CAD+DM, 62+/-4 years, n=28 for all groups) during spontaneous breathing at supine rest. Power (Power(LF)) and median frequency (Med(LF)) of LF oscillations were calculated by power spectral analysis after removing respiratory effects by least-mean-square adaptive filtering. OLDER had higher Power(LF-SBP) (5.5+/-3.0 vs. 3.4+/-2.5 mmHg(2), p=0.002) and lower Power(LF-RRi) than YOUNG (339+/-460 vs. 575+/-422 ms(2), p=0.001) whereas neither variable differed between OLDER and patient groups. Med(LF-SBP) (0.072+/-0.009 vs. 0.080+/-0.011 Hz, p=0.005) and Med(LF-RRi) (0.072+/-0.010 vs. 0.079+/-0.013 Hz, p=0.027) were lower in OLDER compared with YOUNG. Compared with OLDER, Med(LF-RRi) was lower in CAD (0.065+/-0.006 Hz, p=0.015) and CAD +DM (0.066+/-0.008 Hz, p=0.012); whereas CAD+DM had also lower Med(LF-SBP) (0.065+/-0.006 Hz, p=0.012). No differences were observed between OLDER and HT and between CAD and CAD+DM in these variables. We concluded that age is major determinant of the power of LF oscillations in SBP and RRi at rest, whereas the median frequency of these oscillations is altered also by coronary artery disease. PMID- 20573552 TI - Development and validation of an HPLC-FLD method for milbemectin quantification in dog plasma. AB - Milbemectin is a widely used veterinary antiparasitic agent. A high-performance liquid chromatography with fluorescent detection (HPLC-FLD) method is described for the determination of milbemectin in dog plasma. The derivative procedure included mixing 1-methylimizole [MI, MI-ACN (1:1, v/v), 100 microL], trifluoroacetic anhydride [TFAA, TFAA-ACN (1:2, v/v), 150 microL] with a subsequent incubation for 3s at the room temperature to obtain a fluorescent derivative, which is reproducible in different blood samples and the derivatives proved to be stable for at least 80 h at room temperature. HPLC method was developed on C18 column with FLD detection at an excitation wavelength of 365 nm and emission wavelength of 475 nm, with the mobile phase consisting of methanol and water in the ratio of 98:2 (v/v). The assay lower limit of quantification was 1 ng/mL. The calibration curve was linear over concentration range of 1-200 ng/mL. The intra- and inter-day accuracy was >94% and precision expressed as % coefficient of variation was <5%. This method is specific, simple, accurate, precise and easily adaptable to measure milbemycin in blood of other animals. PMID- 20573553 TI - Magazine exposure, tanned women stereotypes, and tanning attitudes. AB - This study investigated whether magazine exposure is related to stereotypical beliefs about tanned women. A survey of White college women (n=205) assessed their exposure to beauty/fashion and health/fitness magazines. Outcome variables were the beliefs that tanned women are fashionable, fit, and shallow. Attention to the tanned women's images in health magazines positively predicted the belief that tanned women are fit and that tanned women are shallow; in contrast, attention to the images in beauty magazine negatively predicted the belief that tanned women are fit. Number of beauty magazines women read negatively predicted the belief that tanned women are shallow. The belief that tanned women are fit was unrelated, but the belief that tanned women are shallow was negatively related, with tanning attitudes. PMID- 20573555 TI - Clavicular pseudoarthrosis, anomalous coronary artery and extra crease of the fifth finger-previously unreported features in individuals with class II 1q21.1 microdeletions. AB - Submicroscopic deletions of two adjacent regions within chromosomal band 1q21.1 were recently associated with two distinct phenotypes: A deleted region of 200 500 kb was found in individuals with Thrombocytopenia Absent Radius syndrome (TAR). Deletion in another region of about 1.25 Mb that is located just telomeric of the TAR region, referred to as distal 1q21.1 region, was found to be associated with a phenotype of cognitive impairment, congenital heart defects and other variable manifestations. A significant proportion of individuals with either of the two deletions did not have phenotypic abnormalities. More than 40 individuals with distal 1q21.1 deletions have been reported to-date. A proportion of them (9 reported individuals) had larger (>2 Mb) deletions involving both the TAR and the distal 1q21.1 regions, referred to as class II deletions. We describe here four additional individuals from two families with such class II deletions, who presented with previously unreported manifestations: clavicular pseudoarthrosis and anomalous origin of the coronary artery in the proband of the first family; an extra transverse crease of the fifth finger, segregating in two of the three deletion carriers in the second family. Previously reported features, associated with such microdeletions - absolute or relative microcephaly, cognitive impairment and short stature, were variably observed in the reported individuals. This report expands the phenotypic spectrum associated with class II 1q21.1 deletions, and demonstrates striking phenotypic variability even within the same family. PMID- 20573551 TI - Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks. AB - The combination of poly(ADP-ribose)polymerase (PARP) inhibitors and alkylating agents is currently being investigated in cancer therapy clinical trials. However, the DNA lesions producing the synergistic cell killing effect in tumors are not fully understood. Treatment of human and mouse fibroblasts with the monofunctional DNA methylating agent methyl methanesulfonate (MMS) in the presence of a PARP inhibitor has been shown to trigger a cell cycle checkpoint response. Among other changes, this DNA damage response to combination treatment includes activation of ATM/Chk2 and phosphorylation of histone H2A.X. These changes are consistent with DNA double-strand break (DSB) formation during the response, but the measurement of DSBs has not been addressed. Such DSB evaluation is important in understanding this DNA damage response because events other than DSB formation are known to lead to ATM/Chk2 activation and H2A.X phosphorylation. Here, we examined the structural integrity of genomic DNA after the combined treatment of cells with MMS and a PARP inhibitor, i.e., exposure to a sub-lethal dose of MMS in the presence of the PARP inhibitor 4-amino-1,8-napthalimide (4 AN). We used pulsed field gel electrophoresis (PFGE) for measurement of DSBs in both human and mouse embryonic fibroblasts, and flow cytometry to follow the phosphorylated form of H2A.X (gamma-H2A.X). The results indicate that DSBs are formed with the combination treatment, but not following treatment with either agent alone. Our data also show that formation of gamma-H2A.X correlates with PARP-1-expressing cells in S-phase of the cell cycle. The observations support the model that persistence of PARP-1 at base excision repair intermediates, as cells move into S-phase, leads to DSBs and the attendant checkpoint responses. PMID- 20573557 TI - Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? AB - Dysfunctional mitochondria are thought to play a cardinal role in the pathogenesis of various neurological disorders, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and stroke. In addition, neuroinflammation is a common denominator of these diseases. Both mitochondrial dysfunction and neuroinflammatory processes lead to increased production of reactive oxygen species (ROS) which are detrimental to neurons. Therefore, neuroinflammation is increasingly recognized to contribute to processes underlying neurodegeneration. Here we describe the involvement of mitochondrial (dys)function in various neurological disorders and discuss the putative link between mitochondrial function and neuroinflammation. PMID- 20573556 TI - Effects of Staphylococcus epidermidis on osteoblast cell adhesion and viability on a Ti alloy surface in a microfluidic co-culture environment. AB - A microfluidic device was used for real time imaging of MC3T3-E1 murine calvarial pre-osteoblasts (osteoblasts) in response to very small numbers of Staphylococcus epidermidis inoculated on the surface of a polished TiAl6V4 alloy in a serum based medium. The Ti alloy surface was integrated to a poly(dimethylsiloxane) fluidic housing with eight 10 MUl channels for high-throughput, cross contamination-free co-culture. In the absence of S. epidermidis osteoblasts were able to adhere, spread, proliferate and remain viable on the Ti alloy surface during a 25 h culture period. With 10(2) or 10(5) colony forming units (cfu) ml( 1) S. epidermidis inoculated on the alloy surface osteoblast adhesion, spreading and proliferation were not adversely affected during the early stages of culture. However, osteoblasts became damaged by the end of culture, as S. epidermidis actively proliferated in the co-culture channels and formed small clusters on the alloy surface. These observations suggest that the small numbers of S. epidermidis did not necessarily compete with osteoblasts for the alloy surface during initial host cell development, but rapid proliferation of the bacteria might have changed the microenvironment, making it unfavorable to sustain the viability of osteoblasts. The results provide a new insight in projecting the potential utility of the microfluidic co-culture approach to developing physiologically and clinically relevant in vitro models of orthopedic implant associated bacterial infection. PMID- 20573558 TI - Depressive behaviour in children diagnosed with a mitochondrial disorder. AB - A higher incidence of depression has been described in adults with primary oxidative phosphorylation disease. We evaluated the psychological characteristics of eighteen non-retarded pediatric patients diagnosed with a disorder of the oxidative phosphorylation. We found significantly higher rate of withdrawn, depressive behaviour compared to population norm scores, to children with other types of inborn errors of metabolism and also in comparison to patients with Sotos syndrome. The occurrence of depressive behaviour showed no correlation with the degree of mitochondrial dysfunction. These findings support the hypothesis that mood disorders could be associated to abnormal cerebral energy metabolism. PMID- 20573559 TI - Pulmonary capillary blood volume and membrane conductance in Andeans and lowlanders at high altitude: a cross-sectional study. AB - Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis. Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied. The latter were studied both at sea level and after acclimatisation to high altitude. Membrane conductance (Dm(CO)) and Vc, corrected for the haemoglobin concentration (Vc(cor)), were calculated using the NO/CO transfer technique. Pulmonary arterial pressure and left atrial pressures were estimated using echocardiography. Highlanders exhibited significantly higher NO and CO transfer than acclimatised lowlanders, with Vc(cor)/VA and Dm(CO)/VA being 49 and 17% greater (VA: alveolar volume) in highlanders, respectively. In acclimatised lowlanders, Dm(CO) and Dm(CO)/VA values were lower at high altitudes than at sea level. Echocardiographic estimates of cardiac output and pulmonary arterial pressure were significantly elevated at high altitudes as compared to sea level. The decrease in Dm(CO) in lowlanders might be due to altered gas transport in the airways due to the low density of air at high altitudes. The disproportionate increase in Vc in Andeans compared to the change in Dm(CO) suggests that the recruitment of capillaries is associated with a thickening of the blood capillary sheet. Since there was no correlation between the increase in Vc and the slight alterations in haemodynamics, this data suggests that chronic hypoxia might stimulate pulmonary angiogenesis in Andeans who live at high altitudes. PMID- 20573560 TI - Spotlight on Aspergillus nidulans photosensory systems. AB - Aspergilli are ubiquitous soil-borne fungi growing within or on the surface of numerous organic substrates. Growth within a substrate or growth on the surface correlates to different growth conditions for the hyphae due to significant changes in oxygen or reactive oxygen species levels and variations in humidity or temperature. The production of air-borne spores is supported by the substrate-air interphase and also requires a sensing system to adapt appropriately. Here we focus on light as important parameter for the mycelium to discriminate between different habitats. The fungal 'eye' includes several light sensors which react to a broad plethora of wavelengths. Aspergillus nidulans light receptors comprise a phytochrome for red-light sensing, white collar-like blue-light signaling proteins, a putative green-light sensing opsin and a cryptochrome/photolyase as distinct sensory systems. Red- and blue-light receptors are assembled into a light-sensing protein complex. Light receptors transmit their signal to a number of other regulatory proteins including a bridging protein, VeA, as part of a trimeric complex. VeA plays a central role in the balance of asexual and sexual development and in the coordination of morphogenesis and secondary metabolism. PMID- 20573561 TI - Hippocampal-cortical structural connectivity disruptions in schizophrenia: an integrated perspective from hippocampal shape, cortical thickness, and integrity of white matter bundles. AB - Disruptions in the hippocampal-cortical functional connectivities have been implicated in schizophrenia but less is known about their anatomical disconnectivities and association with clinical symptoms. We assessed the anatomical relationships between hippocampal shape, cortical thickness, and integrity of white matter bundles interconnecting them in this study. A brain mapping technique, large deformation diffeomorphic metric mapping, was used to analyze structural magnetic resonance imaging and diffusion tensor imaging scans of 126 schizophrenia patients and 77 matched healthy controls. We found that schizophrenia patients had surface inward-deformation in bilateral anterior hippocampi and cortical thinning in the regions of bilateral prefrontal, temporal, and occipital cortices compared with healthy controls. Anterior hippocampal shape deformity was associated with cortical thinning in the brain regions involved in visuo-spatial and verbal memory pathways. Canonical analysis revealed that greater disruptions in the hippocampal-cortical connectivity were associated with more severe negative symptoms in schizophrenia. Furthermore, fractional anisotropy in the fornix and cingulum bundles were reduced indicating abnormal integration of white matter between hippocampus and cortex in schizophrenia. Our findings suggested that aberrant structural hippocampal cortical connectivities may serve as a marker of the illness and provide further structural evidence to support the notion of schizophrenia as a disorder of brain connectivity. PMID- 20573562 TI - Molecular characterization and expression analysis of cathepsin L1 cysteine protease from pearl oyster Pinctada fucata. AB - Cathepsin L is one of the crucial enzyme superfamilies and involved in the immune responses. In this study, a cDNA encoding cathepsin L cysteine protease was identified and characterized from pearl oyster Pinctada fucata (designated as poCL1). The poCL1 cDNA was 1160 bp long and consisted of a 5'-untranslated region (UTR) of 15 bp, a 3'-UTR of 149 bp with a polyadenylation signal (AATAAA) at 11 nucleotides upstream of the poly(A) tail, and an open reading frame (ORF) of 996 bp encoding a polypeptide of 331 amino acids, which contained a typical signal peptide sequence (Met(1)-Ala(16)), a prodomain (Thr(17)-Asp(113)), and a mature domain (Leu(114)-Val(331)). The preproprotein contained the oxyanion hole (Gln), the active triad formed by Cys, His and Asn, and the conserved ERFNIN, GNFD motifs, which is characteristic for cathepsin L proteases. Homology analysis revealed that the poCL1 shared 62.5-72.5% similarity and 42.9-56.0% identity to other known cathepsin L sequences. The phylogenetic tree showed that the poCL1 clustered with the invertebrate cathepsin L cysteine proteases and was closely related to Stichopus japonicus CL, Strongylocentrotus salar CL1 and Radix peregra CL. The mRNA expression of the poCL1 in blank group and bacterial challenge group could be detected in all studied tissues with the higher level in digestive gland. The expression level of poCL1 mRNA was significantly up-regulated at 4 h and 8 h, and then significantly down-regulated at 12 h and 24 h in digestive gland after Vibrio alginolyticus stimulation. These results provided important information for further exploring the roles of pearl oyster cathepsin L in the immune responses. PMID- 20573563 TI - Expression and purification of two different antimicrobial peptides, PR-39 and Protegrin-1 in Escherichia coli. AB - To implement coexpression of antimicrobial peptides PR-39 and Protegrin-1 (PG-1) in prokaryotic expression system, a tandem gene fragment encoding PR-39 and PG-1 has been synthesized chemically. The cleavage site (Asn-Gly) of hydroxylamine hydrochloride was introduced between PR-39 and PG-1. The fragment was inserted into vector pGEX-4T-1 and expressed in Escherichia coli. The fusions of single peptides to GST were created at the same time. The fusion protein GST-PR-39-PG-1, purified by affinity chromatography, was cleaved first by hydroxylamine hydrochloride to release recombinant PG-1 and then by enterokinase to release PR 39. Purification of recombinant PR-39 and PG-1 was achieved. About 1.9 mg/l recombinant PR-39 and 1.1 mg/l PG-1 were obtained. The recombinant antimicrobial peptides showed antibacterial activities that were similar to those released from fusions of single peptides to GST. PMID- 20573565 TI - Wild-type human SOD1 overexpression does not accelerate motor neuron disease in mice expressing murine Sod1 G86R. AB - Approximately 10% of the cases of amyotrophic lateral sclerosis (ALS) are inherited, with the majority of identified linkages in the gene encoding Cu/Zn superoxide dismutase (SOD1). Recent studies showed that human wild-type SOD1 (SOD1(WT)) overexpression accelerated disease in mice expressing human SOD1 mutants linked to ALS. However, there is a controversy whether the exacerbation mechanism occurs through coaggregation of human SOD1(WT) with SOD1 mutants, stabilization by SOD1(WT) of toxic soluble SOD1 species, or conversion of SOD1(WT) into toxic species through oxidative damage. To further address whether the exacerbation of disease requires misfolding, modifications, and/or interaction of SOD1(WT) with pathogenic forms of SOD1 species, we have studied the effect of human SOD1(WT) overexpression in mice expressing the murine mutant Sod1(G86R). Surprisingly, unlike a previous report with SOD1(G85R) mice, SOD1(WT) overexpression did not affect the life span of Sod1(G86R) mice. Our analysis of spinal cord extracts revealed a lack of heterodimerization or aggregation between human SOD1(WT) and mouse Sod1(G86R) proteins. Moreover, there was no evidence of conversion of SOD1(WT) into misfolded or abnormal SOD1 isoforms based on immunoreactivity with monoclonal antibodies specific to misfolded forms of SOD1 mutants and on analysis of SOD1 isoforms after two-dimensional gel electrophoresis. We conclude that a direct interaction between wild type and mutant forms of SOD1 is required for exacerbation of ALS disease by SOD1(WT) protein. PMID- 20573564 TI - A transient kinetic approach to investigate nucleoside inhibitors of mitochondrial DNA polymerase gamma. AB - Nucleoside analogs play an essential role in treating human immunodeficiency virus (HIV) infection since the beginning of the AIDS epidemic and work by inhibition of HIV-1 reverse transcriptase (RT), a viral polymerase essential for DNA replication. Today, over 90% of all regimens for HIV treatment contain at least one nucleoside. Long-term use of nucleoside analogs has been associated with adverse effects including mitochondrial toxicity due to inhibition of the mitochondrial polymerase, DNA polymerase gamma (mtDNA pol gamma). In this review, we describe our efforts to delineate the molecular mechanism of nucleoside inhibition of HIV-1 RT and mtDNA pol gamma based upon a transient kinetic approach using rapid chemical quench methodology. Using transient kinetic methods, the maximum rate of polymerization (k(pol)), the dissociation constant for the ground state binding (K(d)), and the incorporation efficiency (k(pol)/K(d)) can be determined for the nucleoside analogs and their natural substrates. This analysis allowed us to develop an understanding of the structure activity relationships that allow correlation between the structural and stereochemical features of the nucleoside analog drugs with their mechanistic behavior toward the viral polymerase, RT, and the host cell polymerase, mtDNA pol gamma. An in-depth understanding of the mechanisms of inhibition of these enzymes is imperative in overcoming problems associated with toxicity. PMID- 20573566 TI - Anti-inflammatory effects of methanol extract of Patrinia scabiosaefolia in mice with ulcerative colitis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Patrinia scabiosaefolia Fisch is used in folk medicines to treat intestinal abscesses, acute appendicitis, and dysentery in Asia. Although recent reports indicate that Patrinia scabiosaefolia has sedative and anti-tumor effects, its effects on ulcerative colitis have not been previously explored. AIM OF THE STUDY: To determine the effects and the mode of action of the methanol extract of the roots of Patrinia scabiosaefolia (PME) on a model of colitis in mice induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: We induced colitis using DSS in 5-week-ICR mice over 7 days and estimated disease activity index (DAI), which took into account body weight, stool consistency, gross bleeding, and tissue myeloperoxidase (MPO) accumulation. Colon lengths and spleen weights were measured. Histological changes were observed by H&E staining. Pro-inflammatory mediators, namely, nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), were determined using Griess assays, immunoassays, and by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR), respectively. RESULTS: PME significantly attenuated DSS-induced DAI scores and tissue MPO accumulation, which implied that it suppressed weight loss, diarrhea, gross bleeding, and the infiltrations of immune cells. PME administration also effectively and dose-dependently prevented shortening of colon length and enlargement of spleen size. Histological examinations indicated that PME suppressed edema, mucosal damage, and the loss of crypts induced by DSS. Furthermore, PME inhibited the abnormal secretions and mRNA expressions of pro inflammatory cytokines, such as, TNF-alpha, IL-1beta, and IL-6. CONCLUSION: These results suggest that PME has an anti-inflammatory effect at colorectal sites that is due to the down-regulations of the productions and expressions of inflammatory mediators, and that it may have therapeutic value in the setting of inflammatory bowel disease (IBD). PMID- 20573567 TI - Effects of ephedra on autonomic nervous modulation in healthy young adults. AB - AIM OF THE STUDY: Given the popularity of the use of ephedra in traditional Chinese medicine around the world, a greater understanding of its actions is required. This study aims to assess the effects of ephedra on autonomic nervous modulation using power spectral analysis of heart rate variability (HRV). METHODS: This was a randomized, double-blind, placebo-controlled, crossover study. Twenty healthy subjects were given 1g of ephedra dry extract or placebo once per day for 14 days in a crossover fashion with a 7-day washout period between treatments. Sequential HRV measures at baseline and at 30, 60, 120, and 180 min after taking ephedra or the placebo on days 1 and 14 were obtained and compared. In addition, the baseline HRV measurements on days 1, 3, 7, 10, and 14 were also obtained and compared. RESULTS: The normalized low-frequency component (LF%) and the low/high-frequency component ratio (LF/HF) of the HRV were significantly increased, whereas the high-frequency component (HF) and normalized HF (HF%) were significantly decreased at 120 and 180 min after taking ephedra on days 1 and 14. In addition, the baseline LF% and LF/HF were significantly increased, whereas the baseline HF% was significantly decreased on days 10 and 14, as compared to day 1. CONCLUSIONS: By power spectral analysis of the HRV of healthy young adults, it is suggested that ingestion of ephedra dry extract acutely and chronically affects autonomic nervous activity by tilting the sympathovagal balance toward increased sympathetic activity, whereas parasympathetic activity was impaired. PMID- 20573568 TI - Ethnoveterinary knowledge in Navarra (Iberian Peninsula). AB - AIM OF THE STUDY: To collect, analyze and evaluate the ethnoveterinary knowledge about medicinal plants in a northern Iberian region (Navarra, 10,421 km(2), 620,377 inhabitants). METHODOLOGY: Field work was conducted between 2003 and 2007, using semi-structured questionnaire and participant observation as well as transects walks in wild herbal plant collection areas. We performed semi structured interviews with 667 informants (mean age 72; 55.47% women, 44.53% men) in 265 locations, identified the plant reported and analyzed the results, comparing them with those from other territories. RESULTS: Out of 287 species reported to be used in the health field (human and veterinary medicine), 36 are linked to veterinary medicine. 69.4% of these species are new or rarely reported in veterinarian uses. The most frequently used plants were Malva sylvestris, Juglans regia and Verbena officinalis. All different plant parts were used; aerial part was exploited more frequently than other plant parts. Most remedies listed used a single ingredient, typically soaked in water. The route of administration was primarily oral followed by topical applications. These remedies are mostly for cows, calves, sheep, pigs and horses, but cover almost all domestic animal species. The main ailments treated are digestive troubles, wounds and dermatological problems, and respiratory affections. CONCLUSIONS: The folk knowledge about medicinal plant use is still alive in the studied region, and a number of scarcely reported plant uses has been detected, some of them with promising phytotherapeutical applications. PMID- 20573569 TI - Rheological characterization and in vivo evaluation of thermosensitive poloxamer based hydrogel for intramuscular injection of piroxicam. AB - To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel. However, sodium chloride did the opposite. The thermosensitive injectable gel composed of 2.5% piroxicam, 15% P 407, 17% P 188, 0.01% sodium hydroxide and 1.6% sodium chloride was instantly applied to practical industrial product, since it was easy to administer intramuscularly and gelled quickly in the body. The drug was dissolved out of the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. Sodium chloride barely affected the dissolution mechanism or dissolution rate of the drug from the injectable gels. Furthermore, it maintained the plasma concentrations of drug for 4 days and gave a 150-fold higher AUC compared to piroxicam solution. Thus, it would be practically useful for delivering piroxicam in a pattern that allows sustained release for a long time, leading to better bioavailability. PMID- 20573570 TI - Interaction of gatifloxacin with efflux transporters: a possible mechanism for drug resistance. AB - The purpose of the study is to screen the interactions of fourth generation fluoroquinolone-gatifloxacin with efflux pumps, i.e., P-gp, MRP2 and BCRP. Mechanism of gatifloxacin interaction with efflux transporters may explain its acquired resistance. Such clarification may lead to the development of strategies to overcome efflux and enhance its bioavailability at target site. This process will aid in the reduction of dose volume, further eliminating the chances of systemic toxicity from topical gatifloxacin eye drops. MDCK cell lines transfected with the targeted efflux transporters were used for this study. [(14)C] Erythromycin was selected as a model substrate for P-gp and MRP2 whereas Hoechst 33342 was employed as a substrate for BCRP. Uptake and transport studies of these substrates were performed in the presence of gatifloxacin to delineate its interaction with efflux transporters. Further the efflux ratio in the presence of gatifloxacin was calculated from bidirectional transport studies. The concentration of [(14)C] erythromycin and Hoechst 33342 was measured using scintillation counter and fluorescence plate reader, respectively. A concentration dependent inhibition effect in the presence of gatifloxacin was revealed on [(14)C] erythromycin uptake. The efflux ratio (BL-AP/AP-BL) of substrates was found to approach unity at higher gatifloxacin concentrations. Increased concentration of gatifloxacin did not elevate uptake of Hoechst 33342. All these studies were validated with known inhibitors as positive control. Uptake and transport studies support the hypothesis that gatifloxacin is a substrate for P-gp, MRP2 but not for BCRP. Possible interactions of gatifloxacin with P-gp and MRP2 may be a possible mechanism for acquired resistance of gatifloxacin. This information can be further extended to design prodrugs or formulations in order to prevent development of acquired resistance and improve therapeutic efficacy with its reduction in side effects. PMID- 20573571 TI - Uptake and intracellular release kinetics of liposome formulations in glioma cells. AB - Glioblastoma (GBM) is the most malignant primary brain tumor in adults, and its prognosis remains very limited despite decades of research. Enhanced drug delivery to GBM using liposomes represents a promising therapeutic strategy. In this study, we describe a novel cationic and pH-sensitive liposome formulation composed of DPPC:DC-Chol:DOPE:DHPE Oregon Green producing efficient internalization and intracellular delivery to F98 and U-118 GBM cells. With a series of derived modifications of the lipid composition, we investigated the impact of membrane fluidity, steric stabilization and loss of both cationic and pH-sensitive components on cellular uptake and intracellular release kinetics by flow cytometry and confocal microscopy, respectively. DPPC:DC-Chol:DOPE:DHPE Oregon Green liposomes were strongly internalized in both cell lines within 6h. Following cellular uptake, liposomes traveled towards the nucleus (12h) and gradually released their cargo in the cytosol (over 24h). Modifications in liposomal composition of our original formulation had detrimental consequences on both the uptake and intracellular release kinetics in the two tested cell lines. Thus, we report a novel potent liposomal formulation for efficient cytosolic delivery of intracellular therapeutics such as chemotherapy agents and siRNAs to GBM cells. PMID- 20573573 TI - The different performance among motor tasks during the increasing current intensity of deep brain stimulation of the subthalamic nucleus in rats with different degrees of the unilateral striatal lesion. AB - Of all the parameters in the deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the Parkinson disease (PD) animal models, the selection of the stimulation current intensity is alterable and argumentative to affect the stimulation charge or charge density. In order to observe the different performances among several motor tasks during the STN-DBS in rats, we observed the behavioral performance during the stimulation with 0, 100, 150 and 200microA currents. We found that the DBS efficacy reached the climax during the 200microA stimulation at the methamphetamine-induced rotational behavioral test, however at the stepping test and rotarod test, the critical current were 150microA to reach the best improvements. Such findings suggest that the stimulation parameters to reach the climax efficacy among the different symptoms are different during the STN-DBS experiments in rats. The appropriate stimulation parameters should be selected by the symptoms separately according to the aim of each study. PMID- 20573572 TI - Oxytocin and vasopressin immunoreactive staining in the brains of Brandt's voles (Lasiopodomys brandtii) and greater long-tailed hamsters (Tscherskia triton). AB - Immunoreactive (ir) staining of the neuropeptides oxytocin (OT) and vasopressin (AVP) was performed in the brains of Brandt's voles (Lasiopodomys brandtii) and greater long-tailed hamsters (Tscherskia triton)-two species that differ remarkably in social behaviors. Social Brandt's voles had higher densities of OT ir cells in the medial preoptic area (MPOA) and medial amygdala (MeA) as well as higher densities of AVP-ir cells in the lateral hypothalamus (LH) compared to solitary greater long-tailed hamsters. In contrast, the hamsters had higher densities of OT-ir cells in the anterior hypothalamus (AH) and LH and higher densities of AVP-ir cells in the MPOA than the voles. OT-ir and AVP-ir fibers were also found in many forebrain areas with subtle species differences. Given the roles of OT and AVP in the regulation of social behaviors in other rodent species, our data support the hypothesis that species-specific patterns of central OT and AVP pathways may underlie species differences in social behaviors. However, despite a higher density of OT-ir cells in the paraventricular nucleus of the hypothalamus (PVN) in females than in males in both species, no other sex differences were found in OT-ir or AVP-ir staining. These data failed to support our prediction that a sexually dimorphic pattern of neuropeptide staining in the brain is more apparent in Brandt's voles than in greater long-tailed hamsters. PMID- 20573575 TI - The hybrid GLM-ICA investigation on the neural mechanism of acupoint ST36: an fMRI study. AB - Ample clinical reports and neuroimaging studies have demonstrated that the acupuncture has sustained effects after manipulation. However, most previous fMRI studies of acupuncture have paid little attention to this issue, only investigating on the manipulation effects. In the current study, we attempted to explore both acupuncture effects, which have positive influence to therapeutic efficiency, to reveal the neural mechanism of acupuncture. This paper combined the conventional general linear model (GLM) and independent component analysis (ICA) to study the topography and the temporal feature of brain activity to detect the brain responses to stimulation at ST36 (Zusanli) and a sham acupoint. The results showed that the manipulation-related effects and the sustained acupuncture effects separately induced statistically significant increases/decreases in the cortical-subcortical areas, including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) primary/secondary somatosensory cortex (SI/SII), occipital cortices and midbrain. Our findings suggested that the analgesia effects of ST36 integrated sophisticated physiological and psychological procedures. In addition, our results have shed light on methodology in acupuncture research. PMID- 20573574 TI - Cortical thickness is associated with different apolipoprotein E genotypes in healthy elderly adults. AB - Previous studies have consistently suggested that the varepsilon4 allele of apolipoprotein E (APOE) gene is a major risk factor for Alzheimer's disease (AD). However, whether the varepsilon2 allele, a possible protective factor for AD, will express its protective effect in terms of cortical thickness in healthy elderly carriers is unclear. The goal of this study is to clarify the effects of APOE genotypes on cortical thickness in nondemented elderly subjects. We used 164 healthy, cognitively normal, elderly subjects, who were grouped into varepsilon2 carriers, varepsilon3 homozygotes, and varepsilon4 carriers respectively. The APOE varepsilon2 carriers had a significant thicker (corrected p<0.05) cortical thickness in the superior temporal cortex compared with the varepsilon3 homozygotes. In addition to this area, the APOE varepsilon2 carriers had a significantly thicker region in the dorsolateral prefrontal cortex (corrected p<0.05) than did the varepsilon4 carriers. These findings suggest that the different alleles of the APOE gene have distinct neuroanatomic effects in elderly healthy subjects and may play specific roles in the development of AD. PMID- 20573576 TI - Glucocorticoid receptor in the rat epididymis: expression, cellular distribution and regulation by steroid hormones. AB - Glucocorticoids regulate several physiological functions, including reproduction, in mammals. Curiously, little is known about glucocorticoid-induced effects on the epididymis, an androgen-dependent tissue with vital role on sperm maturation. Here, RT-PCR, Western blot and immunohistochemical studies were performed to evaluate expression, cellular distribution and hormonal regulation of glucocorticoid receptor (GR) along rat epididymis. The rat orthologue of human GRalpha (mRNA and protein) was detected in caput, corpus and cauda epididymis and immunolocalized in the nucleus and cytoplasm of different epididymal cells (epithelial, smooth muscle and interstitial cells) and nerve fibers. Changes in plasma glucocorticoid and androgen levels differentially regulated GR expression in caput and cauda epididymis by homologous and heterologous mechanisms. In vivo treatment with dexamethasone significantly changed the expression of glucocorticoid-responsive genes and induced ligand-dependent GR nuclear translocation in epithelial cells from epididymis, indicating that GR is fully active in this tissue. Heterologous regulation of androgen receptor expression by glucocorticoids was also demonstrated in cauda epididymis. Our results demonstrate that the epididymis is under glucocorticoid regulation, opening new insights into the roles of this hormone in male fertility. PMID- 20573577 TI - Anti-atherogenic property of ferulic acid in apolipoprotein E-deficient mice fed Western diet: comparison with clofibrate. AB - Anti-atherogenic effect of ferulic acid (0.02%, w/w) was investigated in comparison with the clofibrate (0.02%, w/w) in apolipoprotein E-deficient (apo E( /-)) mice fed Western diet. Concentrations of total cholesterol (total-C), apolipoprotein B (apo B) in the plasma and epididymal adipose tissue weight were significantly lower in the ferulic acid and clofibrate supplemented groups compared to the control group. The ratio of apo B to apo A-I was also significantly lower in those groups than in the control group. Activities of hepatic ACAT and HMG-CoA reductase were only significantly lower in the ferulic acid and clofibrate groups, respectively than in the control group. The numbers of mice that exhibited aortic fatty plaque were 8/10 in control groups vs. 0/10 in the ferulic acid or clofibrate group. The activities of anti-oxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and paraoxonase) in the hepatocyte and erythrocyte were significantly higher in the ferulic acid group than in the control group. In contrast, hepatic TBARS level was only markedly lower in the ferulic acid group. These results provide a new insight into the anti-atherogenic property of ferulic acid in the apo E(-/-) mice fed a Western diet. PMID- 20573578 TI - Cytoprotective effects of DL-alpha-lipoic acid or squalene on cyclophosphamide induced oxidative injury: an experimental study on rat myocardium, testicles and urinary bladder. AB - The present study aimed to evaluate the role of DL-alpha-lipoic acid (LA) and squalene (SQ) on oxidative cardiac, testicular and urotoxic damage induced by cyclophosphamide (CP). Male Wistar rats were divided into four groups; three groups received a single intraperitoneal injection of CP (200mg/kg BW) to induce toxicity, and two of these groups received either LA (35 mg/kg BW) or SQ (0.4 ml/rat) orally 7 days before and 7 days after CP injection. A vehicle-treated control group was also included. Oxidative damage was observed by decreased serum total antioxidant capacity (TAC) level and abnormal alterations in glutathione peroxidase (GPx) and glutathione reductase (GR) activities, levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and calcium (Ca(+2)) in the heart, testes and urinary bladder of CP-administered rats. Cardiac marker enzyme activities; creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate transaminase (AST) showed severe declines whereas testicular markers; sorbitol dehydrogenase (SDH), gamma-glutamyl transferase (gamma-GT), acid and alkaline phosphatases (ACP and ALP), serum testosterone (T) level and haemoglobin (Hb) absorbance were abnormal. Histopathological observations were also altered. These CP-induced pathological alterations were attenuated by treatment with LA or SQ. These findings highlight the efficacy of LA and SQ as cytoprotectants in CP induced toxicity. PMID- 20573579 TI - 5-HTTLPR moderates effects of current life events on neuroticism: differential susceptibility to environmental influences. AB - Research chronicling links between a polymorphism in the serotonin-transporter gene (5-HTTLPR) and neuroticism has yielded inconsistent results. One possible explanation for this inconsistency is that any gene-phenotype association is obscured by a gene-X-environment (GXE) interaction. We studied a healthy non clinical sample (N=118) to determine whether the 5-HTTLPR interacts with current life events in predicting neuroticism. The differential-susceptibility hypothesis led to the prediction of such an interaction, reflecting the fact that individuals with short alleles would be affected more by both negative and positive life events than those homozygous for long alleles. Participants completed questionnaires concerning recent life events and neuroticism. The 5 HTTLPR was genotyped using a standard protocol with DNA extracted from oral fluid. For those homozygous for the short allele, more negative life events proved related to greater neuroticism, whereas more positive life events proved related to less neuroticism. No such association emerged in the case of those homozygous for the long allele. Whereas neuroticism is likely to be an especially stable trait in individuals homozygous for the long allele, this may be less so the case for those carrying short alleles. PMID- 20573580 TI - Understanding differences in predictions of HPV vaccine effectiveness: A comparative model-based analysis. AB - Mathematical models of HPV vaccine effectiveness and cost-effectiveness have produced conflicting results. The aim of this study was to use mathematical models to compare and isolate the impact of the assumptions most commonly made when modeling the effectiveness of HPV vaccines. Our results clearly show that differences in how we model natural immunity, herd immunity, partnership duration, HPV types, and waning of vaccine protection lead to important differences in the predicted effectiveness of HPV vaccines. These results are important and useful to assist modelers/health economists in choosing the appropriate level of complexity to include in their models, provide epidemiologists with insight on key data necessary to increase the robustness of model predictions, and help decision makers better understand the reasons underlying conflicting results from HPV models. PMID- 20573581 TI - Immunogenic characterization and protection against Streptococcus mutans infection induced by intranasal DNA prime-protein boost immunization. AB - Mucosal immune responses act as the first line of defense against dental caries. In this study, an optimal vaccination strategy was developed to enhance anti caries mucosal immune responses. Mice and rats were vaccinated intranasally firstly with plasmid pCIA-P encoding PAc antigen of Streptococcus mutans and then with rPAc, or with pCIA-P for twice, or with rPAc protein for twice, respectively. The potential of inducing mucosal and systemic immune responses to special antigens was measured by ELISA. In addition, antibody type, cytokine production and protection effectiveness against dental caries were also evaluated. Although all immunized groups developed immune responses, the antibody responses in the DNA prime-protein boost group were stronger compared with those elicited by either the DNA vaccine or the protein vaccine. In particular, the Th1 biased response that was established by the DNA immunization was diverted to Th1/Th2-mixed response following the rPAc protein boost. Moreover, protection against S. mutans challenge was obtained in the rats treated with the DNA prime protein boost regimen, as shown by a significant reduction in dental caries lesion, compared with the control groups immunized with the DNA or protein only. All these findings may provide useful information about effective mucosal vaccines against dental caries. PMID- 20573582 TI - Regulation of human dendritic cells by a novel specific nuclear factor-kappaB inhibitor, dehydroxymethylepoxyquinomicin. AB - Regulation of antigen-presenting cells (APC) is crucial in controlling allograft rejection. Dendritic cells (DC) are the most potent APC and must mature to present antigens to T-cell receptors. During DC maturation, nuclear factor-kappaB (NF-kappaB) is a key transcriptional factor. We synthesized dehydroxymethylepoxyquinomicin (DHMEQ), which specifically inhibits the final step of nuclear translocation of activated NF-kappaB proteins and examined its immunoregulatory effects on human monocyte-derived DC (Mo-DC). Regulatory Mo-DC were generated by pretreatment with DHMEQ before LPS stimulation, which were termed dl-DC. DHMEQ pretreatment (5 microg/ml) completely inhibited nuclear translocation of activated NF-kappaB. DHMEQ significantly inhibited DC production of proinflammatory cytokines (IL-6, TNF-alpha, and IL-12 p70) in a dose-dependent manner. IL-12 was most potently inhibited. However, IL-10 production by dl-DC was only moderately affected by DHMEQ. Although CD40 and the expression of HLA-DR (HLA-DR) expression on dl-DC was downregulated, CD80 and CD86 expression was moderately upregulated. Induction of T helper 1 cell responses was efficiently impaired by dl-DC. This confirmed that DHMEQ-treated Mo-DC exhibited immunoregulatory effects. These findings suggest that DHMEQ has potential as an immunosuppressive drug for human immune cells. PMID- 20573583 TI - Functional changes, increased apoptosis, and diminished nuclear factor-kappaB activity of myeloid dendritic cells during chronic hepatitis C infection. AB - Approximately 70% of patients infected with hepatitis C virus (HCV) develop chronic infections, which have been reported to be caused by impaired specific T cell responses. Myeloid dendritic cells (mDCs) are important antigen-presenting cells that regulate T-cell responses, however their role during chronic hepatitis C (CHC) is not fully understood. In this study, we found that the ability of mDCs to stimulate T-cell responses was impaired in CHC patients. Furthermore, mDCs from CHC patients underwent apoptosis at a higher rate than mDCs from healthy donors. Nuclear factor-kappaB activity, which is critical for mDC function and apoptosis prevention, was diminished in mDCs from CHC patients. In conclusion, mDCs from CHC patients demonstrated functional changes with increased apoptosis, and diminished nuclear factor-kappaB activity. These changes may contribute to the impaired specific T-cell responses in CHC patients. PMID- 20573584 TI - Impaired anticipatory event-related potentials in schizophrenia. AB - Deficits in anticipation are implicated across a variety of cognitive and emotional processes in schizophrenia. Although diminished anticipatory event related potentials (ERPs) have been detected during tasks requiring motor response preparation in schizophrenia, no prior ERP study has examined non-motor related anticipatory processes or used motivationally engaging stimuli. Thirty four schizophrenia outpatients and 36 healthy controls completed a cued, reaction time contingent picture viewing task to assess two types of anticipatory ERPs, one involving motor response preparation (Contingent Negative Variation [CNV]) and one not involving motor preparation (Stimulus Preceding Negativity [SPN]). The ERP paradigm included emotional and non-emotional pictures, and participants also completed trait anhedonia questionnaires. Patients and controls demonstrated similar patterns of reaction time and self-reported emotional responses to the pictures. However, patients demonstrated generally lower CNV and SPN across pleasant, neutral, and unpleasant picture conditions. Patients also reported lower anticipatory pleasure than controls on a trait questionnaire. Schizophrenia patients demonstrate diminished motor- and non-motor-related anticipatory processing, which may have wide-ranging adverse functional consequences. PMID- 20573586 TI - Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis. AB - AIMS: To examine plasma glucagon responses to oral and intravenous (iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM). METHODS: Eleven patients with CP and NGT, 6 patients with CP and secondary IGT, 7 patients with CP and secondary non-insulin requiring DM, and 8 healthy subjects were examined with an oral glucose tolerance test (OGTT) and an iv glucose tolerance test (IVGTT). RESULTS: In the CP groups, significant differences (increasing with the degree of glucose intolerance) in glucagon responses during the first hour of OGTT compared to IVGTT were observed (CP+NGT: 13 + or - 22 vs. -88 + or - 17, p = 0.02; CP+IGT: 3 + or - 17 vs. -87 + or - 19, p = 0.01; CP+DM: 94 + or - 27 vs. -78 + or - 16 1 h x pmol/l (mean + or - SEM), p<0.001). Glucagon was suppressed equally following OGTT and IVGTT in the healthy subjects (-103 + or - 22 vs. -131 + or - 19 1 h x pmol/l; p=NS). IVGTT suppressed glucagon similarly in all groups except for a slightly impaired suppression in the CP+DM-group compared to healthy subjects. CONCLUSIONS: These results suggest that along with the development of secondary glucose intolerance in patients with CP, the suppression of glucagon by oral glucose is gradually lost and substituted by a paradoxical stimulation of secretion, while the suppression by iv glucose is maintained. This might indicate a glucagon stimulatory mechanism of gastrointestinal origin in CP patients. PMID- 20573585 TI - Determining the genetic diversity of lactobacilli from the oral cavity. AB - Several methods for determining the diversity of Lactobacillus spp were evaluated with the purpose of developing a realistic approach for further studies. The patient population was comprised of young children with an oral disease called severe early childhood caries. The ultimate goal of these studies was to ascertain the role of lactobacilli in the caries process. To accomplish that goal, we evaluated several methods and approaches for determining diversity including AP-PCR, chromosomal DNA fingerprinting, denaturing gradient gel electrophoresis, and 16S rRNA gene sequencing. Central to these methods was the gathering and screening of isolates from cultivation medium. Using various estimates of diversity, we addressed the question as to how many isolates represent the overall diversity and how cultivation compares to non-cultivation techniques. Finally, we proposed a working approach for achieving the goals outlined framed by both practical constraints in terms of time, effort and efficacy while yielding a reliable outcome. PMID- 20573587 TI - Training-induced plasticity in rats with cervical spinal cord injury: effects and side effects. AB - We investigated the contribution of corticospinal tract (CST) plasticity to training-induced recovery and side effects following spinal cord injury (SCI). Rats were divided into three lesion groups: a unilateral lesion of the dorsal funiculus, the lateral funiculus or a lesion of the entire dorsolateral quadrant (DLQ). Following surgery, rats were distributed into a training group and an untrained group. Trained rats received rehabilitative training in skilled reaching 6 days a week, starting 4 days post-lesion. Following 6 weeks, all rats were tested in reaching (trained task) and crossing a horizontal ladder (untrained task). We found that trained rats with a lesion involving the dorsal column were significantly better in reaching compared to untrained animals. However, when crossing the horizontal ladder, trained rats made significantly more mistakes than untrained animals. Interestingly, rats with a lateral funiculus lesion did not show either effect. A subsequent ablation of the pyramidal tract (pyramidotomy) in rats with a DLQ-lesion significantly reduced but did not eliminate the reaching success. This spared function suggests that other descending systems contributed to the training-induced recovery. In addition, motor-evoked potentials (MEP) from cortical stimulation could still be evoked after pyramidotomy. Further, blocking synaptic transmission passing through the red nucleus using muscimol did not influence the occurrence of MEP's, suggesting that other descending pathways, like the reticulospinal tract, were involved in functional recovery. In summary, this study demonstrates that training-induced CST plasticity may contribute to recovery of motor function, but may also negatively affect untrained tasks as previously reported. PMID- 20573588 TI - Elevated corticosterone in the amygdala leads to persistent increases in anxiety like behavior and pain sensitivity. AB - Corticosterone (CORT) localized to the amygdala induces anxiety-like behavior coupled with increased behavioral responses to visceral and somatic stimuli. In the current study, we investigated the long-term consequences of briefly exposing the amygdala to elevated levels of CORT with the hypothesis that modulation of the amygdala with CORT results in persistent increases in anxiety-like behavior and viscerosomatic sensitivity. PMID- 20573589 TI - The functional origins of speech-related hand gestures. AB - Many theories of language posit its recent evolution, perhaps contemporaneous with the evolution of Homo sapiens. The embodied language theory, however, in proposing that language includes gestures, provides an avenue for tracing language origins to phylogenetically earlier ancestral species. Here, evidence is presented that the structure of functional hand movements (e.g., reaching for food, climbing a ladder, or crawling), in rats and humans is similar. The structure of these functional hand movements is then compared to speech-related hand gestures in humans. The sequence of language-related gestures are also found to be characteristic of functional hand movements. It is suggested that these findings show that the arm and hand gestures that accompany human speech are derived from the same neural substrates that produce functional movements. Additionally, evidence is reviewed that supports the idea that speech-related gestures resemble the movements elicited by long-train stimulation of the primate motor cortex. Together, this evidence suggests that speech-related hand gestures have their evolutionary origins in functional hand movements of ancestral non primate and primate species and may be constrained by the neural substrate for those movements. These findings are further discussed in relation to the idea that speech-related gestures reflect forelimb motor cortex contributions to embodied language. PMID- 20573590 TI - Augmentation of the behavioural effects of desipramine by repeated immobilization stress. AB - The present report provides evidence that repeated immobilization stress (RIS) induced a noradrenergic-dependent depressive-like behaviour and an augmented behavioural response to desipramine (DMI), a noradrenaline reuptake inhibitor (NRI), in the forced swimming test (FST). The present results show that RIS decreased the baseline of climbing behaviour in the FST. Whereas subchronic administration of DMI (10mg/kg, three times in a 24h period) induced a significantly higher increase in climbing behaviour on repeatedly stressed rats compared to controls. The results also show that the concomitant administration of the low dose of DMI (3mg/Kg) during the RIS fully prevented the decrease of climbing behaviour induced by RIS, without exerting behavioural effects in control rats, further supporting an augmented response to the DMI antidepressant effects in the repeatedly stressed rats. In conclusion, our data indicate that RIS not only changes the behavioural responses in the FST but also increases the antidepressant effects of DMI. PMID- 20573591 TI - Hypothalamic paraventricular 5-hydroxytryptamine inhibits the effects of ghrelin on eating and energy substrate utilization. AB - Ghrelin microinjections into discrete regions of the hypothalamus, including the paraventricular nucleus (PVN), stimulate eating and promote carbohydrate oxidation, effects similar to PVN microinjection of neuropeptide Y (NPY). We have also reported that NPY's orexigenic and metabolic effects are antagonized by pretreatment with 5-hydroxytryptamine (5-HT) or 5-HT receptor agonists. In order to determine whether 5-HT also inhibits ghrelin's orexigenic and metabolic actions, the present study examined the effects of 5-HT pretreatment on ghrelin induced alterations in eating and energy substrate utilization following direct injections into the hypothalamic PVN. Both 5-HT (5-20 nmol) and ghrelin (100 pmol) were administered at the onset of the dark cycle. Food intake was measured 2h postinjection. A separate group of rats (n=8) was injected with 5-HT paired with ghrelin and respiratory quotient (RQ; VCO(2)/VO(2)) was measured over 2h using an open circuit calorimeter. PVN injections of ghrelin increased food intake and increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. 5-HT effectively blocked the effects of ghrelin on both food intake and RQ. We then administered the 5-HT(2A/2C), receptor agonist, DOI, immediately prior to ghrelin. Similar to 5-HT, PVN DOI blocked ghrelin-induced eating and inhibited the peptide's effect on substrate utilization. These data are in agreement with other evidence suggesting that ghrelin functions as a gut-brain peptide in the control of food intake and energy metabolism, and indicate that 5-HT acts within the PVN to modulate ghrelin's orexigenic and metabolic signaling. PMID- 20573592 TI - Binocularity during reading fixations: Properties of the minimum fixation disparity. AB - The present study was based on the physiologically reasonable assumption that the binocular system aims for a reduction of fixation disparity during fixation and that the minimum amount of fixation disparity reflects the optimal binocular status. We measured eye movements (EyeLink II) of 18 participants, while they read 60 sentences from the Potsdam-Sentence-Corpus (PSC) at a viewing distance of 60cm. The minimum fixation disparity was frequently reached directly after the post-saccadic drift, sometimes at the end of fixation and sometimes somewhere in between. Minimum fixation disparity was strongly influenced only by fixation position (within the sentence) while the amplitude of incoming saccade had a negligible effect. Moreover, the effect of fixation position on minimum fixation disparity was correlated with the individual ability to compensate for binocular disconjugacy (due to saccades) while fixating during reading. Generally, we found fixation disparity to be correlated between conditions of reading and fixating single targets, while the reading fixation disparity tended to be more crossed (eso). PMID- 20573593 TI - Sustained eye closure slows saccades. AB - Saccadic eye movements rapidly orient the line of sight towards the object of interest. Pre-motor burst neurons (BNs) controlling saccades receive excitation from superior colliculus and cerebellum, but inhibition by omnipause neurons (OPNs) prevents saccades. When the OPNs pause, BNs begin to fire. It has been presumed that part of the BN burst comes from post-inhibitory rebound (PIR). We hypothesized that in the absence of prior inhibition from OPNs there would be no PIR, and thus the increase in initial firing rate of BNs would be reduced. Consequently, saccade acceleration would be reduced. We measured eye movements and showed that sustained eye closure, which inhibits the activity of OPNs and thus hypothetically should weaken PIR, reduced the peak velocity, acceleration, and deceleration of saccades in healthy human subjects. Saccades under closed eyelids also had irregular trajectories; the frequency of the oscillations underlying this irregularity was similar to that of high-frequency ocular flutter (back-to-back saccades) often seen in normal subjects during attempted fixation at straight ahead while eyes are closed. Saccades and quick phases of nystagmus are generated by the same pre-motor neurons, and we found that the quick-phase velocity of nystagmus was also reduced by lid closure. These changes were not due to a mechanical hindrance to the eyes, because lid closure did not affect the peak velocities or accelerations of the eyes in the "slow-phase" response to rapid head movements of comparable speeds to those of saccades. These results indicate a role for OPNs in generating the abrupt onset and high velocities of saccades. We hypothesize that the mechanism involved is PIR in pre-motor burst neurons. PMID- 20573594 TI - Brown spider venom toxins interact with cell surface and are endocytosed by rabbit endothelial cells. AB - Bites from the Loxosceles genus (brown spiders) cause severe clinical symptoms, including dermonecrotic injury, hemorrhage, hemolysis, platelet aggregation and renal failure. Histological findings of dermonecrotic lesions in animals exposed to Loxosceles intermedia venom show numerous vascular alterations. Study of the hemorrhagic consequences of the venom in endothelial cells has demonstrated that the degeneration of blood vessels results not only from degradation of the extracellular matrix molecule or massive leukocyte infiltration, but also from a direct and primary activity of the venom on endothelial cells. Exposure of an endothelial cell line in vitro to L. intermedia venom induce morphological alterations, such as cell retraction and disadhesion to the extracellular matrix. The aim of the present study was to investigate the interaction between the venom toxins and the endothelial cell surface and their possible internalization, in order to illuminate the information about the deleterious effect triggered by venom. After treating endothelial cells with venom toxins, we observed that the venom interacts with cell surface. Venom treatment also can cause a reduction of cell surface glycoconjugates. When cells were permeabilized, it was possible to verify that some venom toxins were internalized by the endothelial cells. The venom internalization involves endocytic vesicles and the venom was detected in the lysosomes. However, no damage to lysosomal integrity was observed, suggesting that the cytotoxic effect evoked by L. intermedia venom on endothelial cells is not mediated by venom internalization. PMID- 20573595 TI - Sufficiency of the number of segregating sites in the limit under finite-sites mutation. AB - We show that the number of segregating sites is a sufficient statistic for the scaled mutation parameter (theta) in the limit as the number of sites tends to infinity and there is free recombination between sites. We assume that the mutation parameter at each site tends to zero such than the total mutation parameter (theta) is constant in the limit. Our results show that Watterson's estimator is the maximum likelihood estimator in this case, but that it estimates a composite parameter which is different for different mutation models. Some of our results hold when recombination is limited, because Watterson's estimator is an unbiased, method-of-moments estimator regardless of the recombination rate. The quantity it estimates depends on the details of how mutations occur at each site. PMID- 20573597 TI - The synthesis of a major alpha'-mycolic acid of Mycobacterium smegmatis. AB - The synthesis of (2R,3R,Z)-2-docosyl-3-hydroxytetracont-21-enoic acid, a significant alpha'-mycolic acid of Mycobacterium smegmatis and other mycobacteria is reported. PMID- 20573596 TI - Post-treatment circulating plasma BMP6 mRNA and H3K27 methylation levels discriminate metastatic prostate cancer from localized disease. AB - BACKGROUND: We evaluated the utility of post-treatment plasma levels of the circulating bone-morphogenetic protein-6-specific mRNA (cBMP6 mRNA), cell-free DNA (cf-DNA), apoptotic nucleosomes and Histone H3 lysine 27 trimethylation (H3K27me3), in discriminating metastatic prostate cancer (PCa) from organ confined, locally controlled disease. METHODS: Peripheral blood was taken from the patients at the end of therapy, and quantitative PCR was performed to amplify cBMP6 mRNA or cf-DNA from plasma while apoptotic nucleosomes and H3K27me3 were determined by ELISA-based approaches. Following blinded measurements, the markers were compared between the patients with local (n=22), local advanced (n=11) or metastatic disease (n=28). RESULTS: Of the four markers investigated, the cBMP6 mRNA and H3K27me3 levels revealed significant differences between the three subgroups. We found higher levels of cBMP6 mRNA in the patients with metastases than in those with localized (p=0.001) or local advanced disease (p=0.05). When compared to cBMP6, H3K27me3 displayed an inverse distribution and was significantly lower in the patients with metastatic disease than in those with localized (p=0.05) or local advanced disease (p=0.024). There was no correlation between the different markers and total PSA levels or Gleason score at diagnosis. CONCLUSION: Our study provides evidence that post-treatment analysis of cBMP6 mRNA and H3K27me3 may be used to distinguish metastatic PCa from organ confined, locally controlled disease. PMID- 20573598 TI - Neuroprotective effects of emodin in rat cortical neurons against beta-amyloid induced neurotoxicity. AB - Accumulation of beta-amyloid protein (Abeta) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). In this study, the neuroprotective effect of emodin extracted from the traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc against Abeta(25-35)-induced cell death in cultured cortical neurons was investigated. We found that pre-treatment with emodin prevented the cultured cortical neurons from beta-amyloid-induced toxicity. The preventive effect of emodin was blocked by pre-treatment with a phosphatidylinositol-3-kinase (PI3K) pathway inhibitor LY294002 or an estrogen receptor (ER) specific antagonist ICI182780, but not by pre-treatment with an extracellular signal-related kinases (ERK) inhibitor U0126. Furthermore, we found that emodin exposure induced the activation of the Akt serine/threonine kinase and increased the level of Bcl-2 expression. Moreover, the application of emodin for 24h was able to induce the activation of Abeta(25-35)-suppressed Akt and decrease the activation of the Jun-N-terminal kinases (JNK), but not of ERK. Interestingly, the up-regulation of Akt and Bcl-2 did not occur in the presence of LY294002 or ICI182780, suggesting that emodin-up-regulated Bcl-2 is mediated via the ER and PI3K/Akt pathway. Taken together, our results suggest that emodin is an effective neuroprotective drug and is a viable candidate for treating AD. PMID- 20573599 TI - Effect of neurotrophic factors on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose. AB - The purpose of this study was to investigate the effect of brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), and citicoline on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose (HG). The retinas of six adult Sprague-Dawley rats were studied. After the rats were euthanized, the retinas were isolated and cultured in serum-free medium. One group of explants was cultured in normal glucose (NG) and another group in HG medium (HGM). BDNF, NT-4, or citicoline were added to the HGM. After 7 days, the number of regenerating neurites was counted. Then, the explants were fixed, cryosectioned, and stained by TdT-dUTP terminal nick-end labeling (TUNEL), and also immunostained for the active-forms of caspase-3 and -9. The numbers of TUNEL-positive and caspase-3 and -9-immunopositive cells in the ganglion cell layer (GCL) were significantly higher, and the number of regenerating neurites was significantly lower in retinas cultured in HGM than in NG medium. Retinas incubated in HGM supplemented with BDNF, NT-4, or citicoline had significantly lower numbers of TUNEL-positive and caspase-3 and -9-immunopositive cells in the GCL, and the numbers of regenerating neurites were significantly higher than in HGM without these factors. We conclude that the increase in the number of apoptotic cells and decrease the number of regenerating neurites in the HGM indicate that HG is toxic to RGCs. The decrease in the number of apoptotic cells in the HGM containing BDNF, NT-4, or citicoline is correlated with the suppression of the caspase-9 and -3 activities. PMID- 20573600 TI - An ERP investigation of task switching using a flanker paradigm. AB - To investigate whether a task rule carried over from the preceding trial modifies an early portion of the stimulus-locked lateralized readiness potential (sLRP), participants were asked to perform two different flanker tasks that were switched. One task required a left-hand response for a central letter "H" in a five-letter array, and a right-hand response for "S." The stimulus-response rule was reversed for the other task. Reaction times (RTs) were prolonged for switch trials as compared to repeat trials, irrespective of whether stimuli in the five letter array were congruent or incongruent flankers. For the incongruent stimuli, the onset latency of the sLRP was shorter on switch trials compared to repeat trials although the onset for congruent stimuli was delayed on the switch trials. These different sLRP effects as a function of congruent versus incongruent stimuli were interpreted as a manifestation that automatic response activation, dependent on a task rule carried over from a preceding trial, was induced by the early transmission of flanker-related information from stimulus evaluation processes. The finding that the earlier sLRP onset for incongruent stimuli on switch trials did not shorten RTs suggests that RT switch costs are not attributable simply to passive processes. PMID- 20573601 TI - PCBOST: Protein classification based on structural trees. AB - In this paper, we present the protein classification based on structural trees (PCBOST). This is a novel hierarchical classification of proteins that is primarily based on similarity of overall folds of proteins as well as on the modeled folding pathways of proteins. Amino acid sequences, functions of proteins and their evolutionary relationship are not taken into account in this classification. To date the database includes 3847 proteins and domains grouped into six categories having structural similarity and forming six structural trees (total 10,547 PDB-entries). The work on extension of the database and construction of novel structural trees is in progress. The service is free for all users and available at the URL . PMID- 20573602 TI - Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet. AB - A high carbohydrate-high fat (HC-HF) diet-associated with hyperinsulinemia has been previously reported to induce accelerated growth of prostate cancer in a xenograft model. High energy supply and insulin/insulin growth factor-1 axis are two of the mechanisms proposed. We hypothesize that metformin may have a protective effect against prostate cancer progression by affecting metabolisms associated with high energy intake. In the present study, animals were randomized into five groups, receiving a HC-HF diet with 50, 100, or 250mg/kg body weight (mg/kg) metformin in drinking water, a standard diet or HC-HF diet alone. Animals on the HC-HF diet developed obesity and insulin resistance. They had significantly higher body weight, fasting blood glucose at an upper level of normal range, higher insulin secretion and utilization, and fatty degeneration of the liver. Metformin at the doses employed significantly reduced food and water consumption; however, only a dose of 250mg/kg showed a significant reduction in body weight gain and suppression of gluconeogenesis as well remarkably reduced insulin secretion. There was no observed metformin-related hepato-toxicity in any of the groups. In summary, metformin at various doses exhibits protective effects on the metabolic disorder caused by the HC-HF diet with the most effective protection at a dose of 250mg/kg. These effects may explain its translational role relating to its anti-neoplastic potential. PMID- 20573603 TI - Gap junction-mediated spontaneous Ca(2+) waves in differentiated cholinergic SN56 cells. AB - Neuronal gap junctions are receiving increasing attention as a physiological means of intercellular communication, yet our understanding of them is poorly developed when compared to synaptic communication. Using microfluorimetry, we demonstrate that differentiation of SN56 cells (hybridoma cells derived from murine septal neurones) leads to the spontaneous generation of Ca(2+) waves. These waves were unaffected by tetrodotoxin (1microM), but blocked by removal of extracellular Ca(2+), or addition of non-specific Ca(2+) channel inhibitors (Cd(2+) (0.1mM) or Ni(2+) (1mM)). Combined application of antagonists of NMDA receptors (AP5; 100microM), AMPA/kainate receptors (NBQX; 20microM), nicotinic AChR receptors (hexamethonium; 100microM) or inotropic purinoceptors (brilliant blue; 100nM) was also without effect. However, Ca(2+) waves were fully prevented by carbenoxolone (200microM), halothane (3mM) or niflumic acid (100microM), three structurally diverse inhibitors of gap junctions, and mRNA for connexin 36 was detected by PCR. Whole-cell patch-clamp recordings revealed spontaneous inward currents in voltage-clamped cells which we inhibited by Cd(2+), Ni(2+) or niflumic acid. Our data suggest that differentiated SN56 cells generated spontaneous Ca(2+) waves which are propagated by intercellular gap junctions. We propose that this system can be exploited conveniently for the development of neuronal gap junction modulators. PMID- 20573604 TI - Child suicide, family environment, and economic crisis. PMID- 20573606 TI - Sexual behavior, depressive feelings, and suicidality among Estonian school children aged 13 to 15 years. AB - BACKGROUND: The present paper is based on a WHO Collaborative Cross-National Study "Health Behavior in School-Aged Children (HBSC)." AIMS: It aimed at describing and analyzing how the sexual behaviors of 13- to 15-year-old Estonian school children were associated with self-reported depressive feelings and suicidality. Distinctive behavioral traits in relation to age of first sexual intercourse were also investigated. METHODS: Self-reported questionnaires from school children (n = 3,055) were analyzed. RESULTS: In total, 15.2% of school children reported being nonvirgin. Among 13-year-olds, 2.9% of girls and 6.8% of boys were nonvirgins. Approximately 25% of the 15-year-old girls and boys were nonvirgins. The likelihood of depressive feelings and suicidal ideation increased significantly in both genders with loss of virginity. Boys who had lost their virginity at 13 years or younger were 4.2 times more likely to have suicidal thoughts; comparable girls were 7.8 times more likely to have suicidal thoughts. Compared to virgins, youths who had lost their virginity reported poor self assessed health and more risk behaviors in themselves and their peers. CONCLUSION: Experiences of sexual intercourse increased the odds ratios for depressive feelings and suicidality. The earlier sexual intercourse was initiated, the greater were the odds of lower mental well-being. Risk behaviors emerged as a complex phenomenon requiring complex prevention. PMID- 20573607 TI - Validity of proxy-based reports of impulsivity and aggression in Chinese research on suicidal behavior. AB - BACKGROUND: In studies about the risk factors for suicidal behavior, the assessment of impulsiveness and aggression often depend on information from proxy informants. AIMS: To assess the validity of proxy informants' reports on impulsiveness and aggression in China. METHODS: Modified Chinese versions of the Barratt Impulsiveness Scale (BIS-CV) and the Buss-Perry Aggression Questionnaire (AQ-CV) were administered to 131 suicide attempters treated at a hospital in rural China, to coresident relatives about the attempters, to 131 matched community controls, and to coresident relatives about the controls. RESULTS: BIS CV and AQ-CV total scores and subscale scores were all significantly higher for suicide attempters than for matched controls. Proxy informants considered subjects slightly more impulsive and aggressive than the subjects reported themselves. Subject-proxy concordance for total BIS-CV and AQ-CV scores were excellent for both attempters and controls (ICCs = 0.76-0.83). Concordance for the three BIS-CV subscales was 0.74-0.81 for attempters and 0.74-0.83 for controls. Concordance for the five AQ-CV subscales was 0.66-0.85 for attempters and 0.56-0.82 for controls. LIMITATIONS: Results are based on respondents from a single location in rural China. CONCLUSIONS: The results support the validity of the BIS-CV and AQ-CV and of research on suicidal behavior in China that uses proxy-based reports of impulsiveness and aggression. PMID- 20573605 TI - Body investment, depression, and alcohol use as risk factors for suicide proneness in college students. AB - BACKGROUND: Individuals who are less invested in their bodies, experiencing symptoms of depression, and consuming alcohol are at increased risk for engaging in suicidal behaviors. AIMS: This study examined the relationships among three risk factors - body investment, depression, and alcohol use - and suicide proneness as measured by the Life Attitudes Schedule - Short Form (LAS-SF) in college students (N = 318). METHODS: Path analysis was used to construct a causal model of suicide proneness. The Body Investment Scale (BIS) subscales were assumed to be causally prior to depression, which was in turn modeled as occurring prior to alcohol use, which was in turn modeled as prior to suicide proneness. RESULTS: As expected, suicide proneness was positively predicted by alcohol use, alcohol use was positively predicted by depression, and depression was negatively predicted by the body image component of the BIS. Additionally, the body image-suicide proneness link was significantly mediated by depression and its direct effect on suicide proneness as well as by the two-mediator path of body image on depression on drinking on suicide proneness. CONCLUSIONS: Implications are offered for the improved identification and treatment of young adults at risk for suicidal and health-diminishing behaviors. PMID- 20573608 TI - Participant roles in bullying behavior and their association with thoughts of ending one's life. AB - BACKGROUND: Studies have shown that students who are bullied at school are at an increased risk of poor mental health and suicide. Little is known, however, about those who have other participant roles in bullying interactions (e.g., bystanders). AIMS: To better understand the implications exposure to bullying has upon thoughts of ending life among students who have multiple participant roles. METHODS: This study was a cross-sectional survey of a representative sample of 2,002 students (55% boys, 45% girls) aged 12 to 16 years (M = 13.60, SD = 1.06) attending 14 schools in the North of England. RESULTS: The majority of students in this study were involved in bullying behavior at school as victims, bullies, bystanders, or a combination of all three. Those with multiple roles (victim, bully, and bystander) were significantly more likely to report having had thoughts of ending their life. CONCLUSIONS: The findings from this study have significant implications for clinicians, educational, and school psychologists working with students involved in bullying behavior. Whole school antibullying initiatives are necessary to reduce the psychological distress and thoughts of ending life found among members of the school population. Further studies exploring covictimization among bystanders and revictimization among former victims of bullying are recommended. PMID- 20573609 TI - Does a brief suicide prevention gatekeeper training program enhance observed skills? AB - BACKGROUND: Suicide is a significant public health problem worldwide that requires evidence-based prevention efforts. One approach to prevention is gatekeeper training. Gatekeeper training programs for community members have demonstrated positive changes in knowledge and attitudes about suicide. Changes in gatekeeper skills have not been well established. AIMS: To assess and to predict the impact of a brief, gatekeeper training on community members' observed skills. METHODS: Participants in a community gatekeeper training were employees at US universities. 50 participants were randomly selected for skills assessment and videotaped interacting with a standardized actor prior to and following training. Tapes were reliably rated for general and suicide-specific skills. RESULTS: Gatekeeper skills increased from pre- to posttest: 10% of participants met criteria for acceptable gatekeeper skills before training, while 54% met criteria after training. Pretraining variables did not predict increased skills. LIMITATIONS: Results do not provide conclusions about the relationship between observed gatekeeper skills and actual use of those skills in the future. CONCLUSIONS: Gatekeeper training enhances suicide-specific skills for the majority of participants. Other strategies, such as behavioral rehearsal, may be necessary to enhance skills in the remaining participants. PMID- 20573610 TI - Child and adolescent suicides in Bosnia and Herzegovina before and after the war (1992-1995). AB - BACKGROUND: Evidence on youth suicides from Southeastern Europe is scarce. We are not aware of previous reports from Bosnia and Herzegovina, which experienced war from 1992 to 1995. Durkheim's theory of suicide predicts decreased suicide rates in wartime and increased rates afterward. AIMS: To compare child and adolescent suicides in Bosnia and Herzegovina before and after the war. METHODS: Data on youth suicide for prewar (1986-90) and postwar (2002-06) periods were analyzed with respect to prevalence, sex and age differences, and suicide methods. Suicide data from 1991 through 2001 were not available. RESULTS: Overall youth suicide rates were one-third lower in the postwar than in the prewar period. This effect was most pronounced for girls, whose postwar suicide rates almost halved, and for 15-19-year-old boys, whose rates decreased by about a one-fourth. Suicides increased among boys aged 14 or younger. Firearm suicides almost doubled proportionally and were the predominant postwar method, while the most common prewar method had been hanging. CONCLUSIONS: The findings from this study indicate the need for public education in Bosnia and Herzegovina on the role of firearm accessibility in youth suicide and for instructions on safe storage in households. Moreover, raising societal awareness about suicide risk factors and suicide prevention is needed. PMID- 20573613 TI - Neurological picture. Vertebral sarcoidosis mimicking metastases. PMID- 20573614 TI - Hormonal correlates of individual quality in a long-lived bird: a test of the 'corticosterone-fitness hypothesis'. AB - Measuring individual quality in vertebrates is difficult. Focusing on allostasis mechanisms may be useful because they are functionally involved in the ability of an individual to survive and reproduce in its environment. Thus, a rise in stress hormones levels (corticosterone) occurs when an organism has to cope with challenging environmental conditions. This has recently led to the proposal of the 'cort-fitness hypothesis', which suggests that elevated baseline corticosterone levels should be found in individuals of poor quality that have difficulty coping with their environment. We tested this hypothesis by comparing an integrative measure of individual quality to baseline corticosterone in black browed albatrosses (Thalassarche melanophrys). We found that individual baseline corticosterone levels were related to individual quality and highly repeatable from one breeding season to the next. Importantly, this relationship was found in males, but not in females. Therefore, we suggest that the relationship between quality and baseline corticosterone levels may depend on the environmental and energetic constraints that individuals have to cope with. PMID- 20573615 TI - Qualitative assessment of the diet of European eel larvae in the Sargasso Sea resolved by DNA barcoding. AB - European eels (Anguilla anguilla) undertake spawning migrations of more than 5000 km from continental Europe and North Africa to frontal zones in the Sargasso Sea. Subsequently, the larval offspring are advected by large-scale eastward ocean currents towards continental waters. However, the Sargasso Sea is oligotrophic, with generally low plankton biomass, and the feeding biology of eel larvae has so far remained a mystery, hampering understanding of this peculiar life history. DNA barcoding of gut contents of 61 genetically identified A. anguilla larvae caught in the Sargasso Sea showed that even the smallest larvae feed on a striking variety of plankton organisms, and that gelatinous zooplankton is of fundamental dietary importance. Hence, the specific plankton composition seems essential for eel larval feeding and growth, suggesting a linkage between eel survival and regional plankton productivity. These novel insights into the prey of Atlantic eels may furthermore facilitate eel larval rearing in aquaculture, which ultimately may replace the unsustainable use of wild-caught glass eels. PMID- 20573616 TI - Favouritism in the motor system: social interaction modulates action simulation. AB - The ability to anticipate others' actions is crucial for social interaction. It has been shown that this ability relies on motor areas of the human brain that are not only active during action execution and action observation, but also during anticipation of another person's action. Recording electroencephalograms during a triadic social interaction, we assessed whether activation of motor areas pertaining to the human mirror-neuron system prior to action observation depends on the social relationship between the actor and the observer. Anticipatory motor activation was stronger when participants expected an interaction partner to perform a particular action than when they anticipated that the same action would be performed by a third person they did not interact with. These results demonstrate that social interaction modulates action simulation. PMID- 20573617 TI - Brevity is not always a virtue in primate communication. AB - Semple et al. (Semple et al. in press, Biol. Lett. (doi:10.1098/rsbl.2009.1062)) argued that the 'law of brevity' (an inverse relationship between word length and frequency of use) applies not only to human language but also to vocal signalling in non-human primates, because coding efficiency is paramount in both situations. We analysed the frequency of use of signals of different duration in the vocal repertoires of two Neotropical primate species studied in the wild-the common marmoset (Callithrix jacchus) and the golden-backed uakari (Cacajao melanocephalus). The key prediction of the law of brevity was not supported in either species: although the most frequently emitted calls were relatively brief, they were not the shortest signals in the repertoire. The costs and benefits associated with signals of different duration must be appreciated to understand properly their frequency of use. Although relatively brief vocal signals may be favoured by natural selection in order to minimize energetic costs, the very briefest signals may be ambiguous, contain reduced information or be difficult to detect or locate, and may therefore be selected against. Analogies between human language and vocal communication in animals can be misleading as a basis for understanding frequency of use, because coding efficiency is not the only factor of importance in animal communication, and the costs and benefits associated with different signal durations will vary in a species-specific manner. PMID- 20573618 TI - Kin recognition and adjustment of reproductive effort in zebra finches. AB - The differential allocation theory predicts that females should invest more in offspring produced with attractive partners, and a number of studies support this prediction in birds. Females have been shown to increase reproductive investment when mated to males showing elaborated sexual traits. However, mate attractiveness might also depend on the interaction between male and female genotypes. Accordingly, females should invest more in offspring sired by individuals that are genetically dissimilar or carry superior alleles. Here, we show in zebra finches (Taeniopygia guttata) that pairs of unfamiliar genetic brothers and sisters are less likely to reproduce in comparison with randomly mated pairs. Among the brother-sister pairs, those that attempted to breed laid smaller clutches and of lower total clutch mass. Our results provide the first experimental evidence that females adjust their reproductive effort in response to the genetic similarity of their partners. Importantly, these results imply a female ability to assess relatedness of a social mate without prior association. PMID- 20573619 TI - Sea turtle nesting distributions and oceanographic constraints on hatchling migration. AB - Patterns of abundance across a species's reproductive range are influenced by ecological and environmental factors that affect the survival of offspring. For marine animals whose offspring must migrate long distances, natural selection may favour reproduction in areas near ocean currents that facilitate migratory movements. Similarly, selection may act against the use of potential reproductive areas from which offspring have difficulty emigrating. As a first step towards investigating this conceptual framework, we analysed loggerhead sea turtle (Caretta caretta) nest abundance along the southeastern US coast as a function of distance to the Gulf Stream System (GSS), the ocean current to which hatchlings in this region migrate. Results indicate that nest density increases as distance to the GSS decreases. Distance to the GSS can account for at least 90 per cent of spatial variation in regional nest density. Even at smaller spatial scales, where local beach conditions presumably exert strong effects, at least 38 per cent of the variance is explained by distance from the GSS. These findings suggest that proximity to favourable ocean currents strongly influences sea turtle nesting distributions. Similar factors may influence patterns of abundance across the reproductive ranges of diverse marine animals, such as penguins, eels, salmon and seals. PMID- 20573620 TI - Female and male genetic contributions to post-mating immune defence in female Drosophila melanogaster. AB - Post-mating reduction in immune defence is common in female insects, and a trade off between mating and immunity could affect the evolution of immunity. In this work, we tested the capacity of virgin and mated female Drosophila melanogaster to defend against infection by four bacterial pathogens. We found that female D. melanogaster suffer post-mating immunosuppression in a pathogen-dependent manner. The effect of mating was seen after infection with two bacterial pathogens (Providencia rettgeri and Providencia alcalifaciens), though not after infection with two other bacteria (Enterococcus faecalis and Pseudomonas aeruginosa). We then asked whether the evolution of post-mating immunosuppression is primarily a 'female' or 'male' trait by assaying for genetic variation among females for the degree of post-mating immune suppression they experience and among males for the level of post-mating immunosuppression they elicit in their mates. We also assayed for an interaction between male and female genotypes to test the specific hypothesis that the evolution of a trade-off between mating and immune defence in females might be being driven by sexual conflict. We found that females, but not males, harbour significant genetic variation for post-mating immunosuppression, and we did not detect an interaction between female and male genotypes. We thus conclude that post-mating immune depression is predominantly a 'female' trait, and find no evidence that it is evolving under sexual conflict. PMID- 20573621 TI - A comparison between coral colonies of the genus Madracis and simulated forms. AB - In addition to experimental studies, computational models provide valuable information about colony development in scleractinian corals. Using our simulation model, we show how environmental factors such as nutrient distribution and light availability affect growth patterns of coral colonies. To compare the simulated coral growth forms with those of real coral colonies, we quantitatively compared our modelling results with coral colonies of the morphologically variable Caribbean coral genus Madracis. Madracis species encompass a relatively large morphological variation in colony morphology and hence represent a suitable genus to compare, for the first time, simulated and real coral growth forms in three dimensions using a quantitative approach. This quantitative analysis of three-dimensional growth forms is based on a number of morphometric parameters (such as branch thickness, branch spacing, etc.). Our results show that simulated coral morphologies share several morphological features with real coral colonies (M. mirabilis, M. decactis, M. formosa and M. carmabi). A significant correlation was found between branch thickness and branch spacing for both real and simulated growth forms. Our present model is able to partly capture the morphological variation in closely related and morphologically variable coral species of the genus Madracis. PMID- 20573622 TI - Condition-dependent ejaculate size and composition in a ladybird beetle. AB - Sexually selected male ejaculate traits are expected to depend on the resource state of males. Theory predicts that males in good condition will produce larger ejaculates, but that ejaculate composition will depend on the relative production costs of ejaculate components and the risk of sperm competition experienced by low- and high-condition males. Under some conditions, when low condition leads to poorer performance in sperm competition, males in low condition may produce ejaculates with higher sperm content relative to their total ejaculate and may even transfer more sperm than high-condition males in an absolute sense. Previous studies in insects have shown that males in good condition transfer larger ejaculates or more sperm, but it has not been clear whether increased sperm content represents a shift in allocation or simply a larger ejaculate, and thus the condition dependence of ejaculate composition has been largely untested. We examined condition dependence in ejaculate by manipulating adult male condition in a ladybird beetle (Adalia bipunctata) in which males transfer three distinct ejaculate components during mating: sperm, non-sperm ejaculate retained within the female reproductive tract, and a spermatophore capsule that females eject and ingest following mating. We found that high condition males indeed transferred larger ejaculates, potentially achieved by an increased rate of ejaculate transfer, and allocated less to sperm compared with low-condition males. Low condition males transferred ejaculates with absolutely and proportionally more sperm. This study provides the first experimental evidence for a condition dependent shift in ejaculate composition. PMID- 20573623 TI - Learning in a game context: strategy choice by some keeps learning from evolving in others. AB - Behavioural decisions in a social context commonly have frequency-dependent outcomes and so require analysis using evolutionary game theory. Learning provides a mechanism for tracking changing conditions and it has frequently been predicted to supplant fixed behaviour in shifting environments; yet few studies have examined the evolution of learning specifically in a game-theoretic context. We present a model that examines the evolution of learning in a frequency dependent context created by a producer-scrounger game, where producers search for their own resources and scroungers usurp the discoveries of producers. We ask whether a learning mutant that can optimize its use of producer and scrounger to local conditions can invade a population of non-learning individuals that play producer and scrounger with fixed probabilities. We find that learning provides an initial advantage but never evolves to fixation. Once a stable equilibrium is attained, the population is always made up of a majority of fixed players and a minority of learning individuals. This result is robust to variation in the initial proportion of fixed individuals, the rate of within- and between generation environmental change, and population size. Such learning polymorphisms will manifest themselves in a wide range of contexts, providing an important element leading to behavioural syndromes. PMID- 20573625 TI - Oceanic fronts in the Sargasso Sea control the early life and drift of Atlantic eels. AB - Anguillid freshwater eels show remarkable life histories. In the Atlantic, the European eel (Anguilla anguilla) and American eel (Anguilla rostrata) undertake extensive migrations to spawn in the oceanic Sargasso Sea, and subsequently the offspring drift to foraging areas in Europe and North America, first as leaf-like leptocephali larvae that later metamorphose into glass eels. Since recruitment of European and American glass eels has declined drastically during past decades, there is a strong demand for further understanding of the early, oceanic phase of their life cycle. Consequently, during a field expedition to the eel spawning sites in the Sargasso Sea, we carried out a wide range of dedicated bio-physical studies across areas of eel larval distribution. Our findings suggest a key role of oceanic frontal processes, retaining eel larvae within a zone of enhanced feeding conditions and steering their drift. The majority of the more westerly distributed American eel larvae are likely to follow a westerly/northerly drift route entrained in the Antilles/Florida Currents. European eel larvae are generally believed to initially follow the same route, but their more easterly distribution close to the eastward flowing Subtropical Counter Current indicates that these larvae could follow a shorter, eastward route towards the Azores and Europe. The findings emphasize the significance of oceanic physical-biological linkages in the life-cycle completion of Atlantic eels. PMID- 20573624 TI - Evolutionary bet-hedging in the real world: empirical evidence and challenges revealed by plants. AB - Understanding the adaptations that allow species to live in temporally variable environments is essential for predicting how they may respond to future environmental change. Variation at the intergenerational scale can allow the evolution of bet-hedging strategies: a novel genotype may be favoured over an alternative with higher arithmetic mean fitness if the new genotype experiences a sufficiently large reduction in temporal fitness variation; the successful genotype is said to have traded off its mean and variance in fitness in order to 'hedge its evolutionary bets'. We review the evidence for bet-hedging in a range of simple plant systems that have proved particularly tractable for studying bet hedging under natural conditions. We begin by outlining the essential theory, reiterating the important distinction between conservative and diversified bet hedging strategies. We then examine the theory and empirical evidence for the canonical example of bet-hedging: diversification via dormant seeds in annual plants. We discuss the complications that arise when moving beyond this simple case to consider more complex life-history traits, such as flowering size in semelparous perennial plants. Finally, we outline a framework for accommodating these complications, emphasizing the central role that model-based approaches can play. PMID- 20573626 TI - Crime and punishment in a roaming cleanerfish. AB - Cheating is common in cooperative interactions, but its occurrence can be controlled by various means ranging from rewarding cooperators to active punishment of cheaters. Punishment occurs in the mutualism involving the cleanerfish Labroides dimidiatus and its reef fish clients. When L. dimidiatus cheats, by taking scales and mucus rather than ectoparasites, wronged clients either chase or withhold further visits to the dishonest cleaner, which leads to more cooperative future interactions. Punishment of cheating L. dimidiatus may be effective largely because these cleaners are strictly site-attached, increasing the potential for repeated interactions between individual cleaners and clients. Here, we contrast the patterns of cheating and punishment in L. dimidiatus with its close relative, the less site-attached Labroides bicolor. Overall, L. bicolor had larger home ranges, cheated more often and, contrary to our prediction, were punished by cheated clients as frequently as, and not less often than, L. dimidiatus. However, adult L. bicolor, which had the largest home ranges, did not cheat more than younger conspecifics, suggesting that roaming, and hence the frequency of repeated interactions, has little influence on cheating and retaliation in cleaner-client relationships. We suggest that roaming cleaners offer the only option available to many site-attached reef fish seeking a cleaning service. This asymmetry in scope for partner choice encourages dishonesty by the partner with more options (i.e. L. bicolor), but to be cleaned by a cleaner that sometimes cheats may be a better option than not to be cleaned at all. PMID- 20573627 TI - Diet and hormonal manipulation reveal cryptic genetic variation: implications for the evolution of novel feeding strategies. AB - When experiencing resource competition or abrupt environmental change, animals often must transition rapidly from an ancestral diet to a novel, derived diet. Yet, little is known about the proximate mechanisms that mediate such rapid evolutionary transitions. Here, we investigated the role of diet-induced, cryptic genetic variation in facilitating the evolution of novel resource-use traits that are associated with a new feeding strategy--carnivory--in tadpoles of spadefoot toads (genus Spea). We specifically asked whether such variation in trophic morphology and fitness is present in Scaphiopus couchii, a species that serves as a proxy for ancestral Spea. We also asked whether corticosterone, a vertebrate hormone produced in response to environmental signals, mediates the expression of this variation. Specifically, we compared broad-sense heritabilities of tadpoles fed different diets or treated with exogenous corticosterone, and found that novel diets can expose cryptic genetic variation to selection, and that diet induced hormones may play a role in revealing this variation. Our results therefore suggest that cryptic genetic variation may have enabled the evolutionary transition to carnivory in Spea tadpoles, and that such variation might generally facilitate rapid evolutionary transitions to novel diets. PMID- 20573628 TI - Optimal viral strategies for bypassing RNA silencing. AB - The RNA silencing pathway constitutes a defence mechanism highly conserved in eukaryotes, especially in plants, where the underlying working principle relies on the repressive action triggered by the intracellular presence of double stranded RNAs. This immune system performs a post-transcriptional suppression of aberrant mRNAs or viral RNAs by small interfering RNAs (siRNAs) that are directed towards their target in a sequence-specific manner. However, viruses have evolved strategies to escape from silencing surveillance while promoting their own replication. Several viruses encode suppressor proteins that interact with different elements of the RNA silencing pathway and block it. The different suppressors are not phylogenetically nor structurally related and also differ in their mechanism of action. Here, we adopt a model-driven forward-engineering approach to understand the evolution of suppressor proteins and, in particular, why viral suppressors preferentially target some components of the silencing pathway. We analysed three strategies characterized by different design principles: replication in the absence of a suppressor, suppressors targeting the first protein component of the pathway and suppressors targeting the siRNAs. Our results shed light on the question of whether a virus must opt for devoting more time into transcription or into translation and on which would be the optimal step of the silencing pathway to be targeted by suppressors. In addition, we discussed the evolutionary implications of such designing principles. PMID- 20573629 TI - Optimization of the sintering atmosphere for high-density hydroxyapatite-carbon nanotube composites. AB - Hydroxyapatite-carbon nanotube (HA-CNT) composites have the potential for improved mechanical properties over HA for use in bone graft applications. Finding an appropriate sintering atmosphere for this composite presents a dilemma, as HA requires water in the sintering atmosphere to remain phase pure and well hydroxylated, yet CNTs oxidize at the high temperatures required for sintering. The purpose of this study was to optimize the atmosphere for sintering these composites. While the reaction between carbon and water to form carbon monoxide and hydrogen at high temperatures (known as the 'water-gas reaction') would seem to present a problem for sintering these composites, Le Chatelier's principle suggests this reaction can be suppressed by increasing the concentration of carbon monoxide and hydrogen relative to the concentration of carbon and water, so as to retain the CNTs and keep the HA's structure intact. Eight sintering atmospheres were investigated, including standard atmospheres (such as air and wet Ar), as well as atmospheres based on the water-gas reaction. It was found that sintering in an atmosphere of carbon monoxide and hydrogen, with a small amount of water added, resulted in an optimal combination of phase purity, hydroxylation, CNT retention and density. PMID- 20573630 TI - Spatial dynamics of the 1918 influenza pandemic in England, Wales and the United States. AB - There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale. To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries. For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty. PMID- 20573631 TI - Effect of neuraxial anaesthesia on tumour progression in cervical cancer patients treated with brachytherapy: a retrospective cohort study. AB - BACKGROUND: Recent evidence suggests that neuraxial and regional anaesthesia may influence the progression of the underlying malignant disease after surgery. METHODS: This retrospective cohort study assessed whether neuraxial anaesthesia would affect the progression of cervical cancer in 132 consecutive patients who were treated with brachytherapy in a tertiary cancer centre in Australia. RESULTS: Age, American Society of Anesthesiologists status, International Federation of Gynecologists and Obstetricians (FIGO) cancer staging, invasion into the uterus, tumour volume, and tumour cell types were not significantly different between patients who received neuraxial and general anaesthesia during their first brachytherapy treatment. The use of neuraxial anaesthesia during the first brachytherapy was not associated with a reduced risk of local or systemic recurrence [hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.54-1.67; P=0.863], long-term mortality from tumour recurrence (HR 1.46, 95% CI 0.75-2.84; P=0.265), or all-cause mortality (HR 1.46, 95% CI 0.81-2.61; P=0.209), after adjusting for other prognostic factors. Tumour recurrence and long-term survival were only significantly associated with the tumour cell type, tumour volume, and FIGO tumour staging. Sensitivity analyses using proportions of all brachytherapy sessions performed under neuraxial anaesthesia also did not show any beneficial effects of neuraxial anaesthesia on tumour recurrence and long-term survival. CONCLUSIONS: Using neuraxial anaesthesia during brachytherapy for patients with cervical cancer was not associated with a reduced risk of tumour recurrence and mortality when compared with general anaesthesia. PMID- 20573632 TI - Surgical stress index in response to pacemaker stimulation or atropine. AB - BACKGROUND: The surgical stress index (SSI) is a new monitoring tool for the assessment of nociception during general anaesthesia. It is calculated based on the heart beat interval and the pulse wave amplitude. Correlation of SSI with nociceptive stimuli and opioid effect-site concentrations has been demonstrated, but the influence of isolated modulation of heart rate (HR) on SSI is still unclear. The aim of this study was to evaluate the effect on SSI of atropine administration and cardiac pacing. METHODS: In 18 anaesthetized ASA III ICU patients, either repetitive cardiac pacemaker stimulation or administration of atropine (10 microg kg(-1)) was performed, and the effect on SSI, arterial pressure, spectral entropy, and bispectral index was analysed. RESULTS: Cardiac pacing at 100 beats min(-1) was followed by an increase in SSI from 26 [17-35 (10 41)] to 59 [53-72 (48-78)] {median [inter-quartile range (range)]} (P=0.0006), whereas other variables remained unaffected. Also, atropine administration increased SSI from 27 [20-34 (16-39)] to 58 [48-70 (41-81)] (P=0.007) without significant effect on other variables except HR. A recalibration of SSI during cardiac pacing leads to a significant decrease in SSI to 49 [40-52 (36-57)] (P=0.03), whereas recalibration after atropine administration had no effect. CONCLUSIONS: SSI values measured in patients receiving atropine or in patients with pacemakers should be interpreted cautiously. PMID- 20573633 TI - Influence of propofol-opioid vs isoflurane-opioid anaesthesia on postoperative troponin release in patients undergoing coronary artery bypass grafting. AB - BACKGROUND: In experimental and clinical studies, volatile anaesthesia has proven to possess cardioprotective properties. However, no randomized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available. We therefore compared isoflurane-sufentanil vs propofol-sufentanil anaesthesia in patients undergoing coronary artery bypass grafting. METHODS: One hundred patients were randomly assigned to receive isoflurane-sufentanil (I) (n = 51) or propofol-sufentanil (P) (n = 49) anaesthesia, aimed at the same hypnotic depth. Postoperative concentrations of cardiac troponin I (cTnI) were followed for 72 h. Secondary outcome variables were length of stay (LOS) in the intensive care unit (ICU) and in hospital, and 30 day and 1 yr mortality and morbidity, defined as acute myocardial infarction, arrhythmias, and cardiac dysfunction. Groups were compared by an on-treatment analysis, using linear mixed models for repeated measures. RESULTS: Eighty-four patients completed the protocol (I: 41 vs P: 43). Postoperative cTnI concentrations increased to a maximum of I: 2.72 ng ml(-1) (1.78-5.85) and P: 2.64 ng ml(-1) (1.67-4.83), but did not differ between groups (P=0.11). LOS in the ICU and in hospital was similar [ICU I: 18 (17.0 21.5) vs P: 19 (17.0-22.0) h; hospital I: 9 (6.5-8.0) vs P: 8 (6.0-9.0) days]. Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups. One year after surgery, two patients had died of non cardiac causes. No between-group differences in cardiac morbidity were found. CONCLUSIONS: In this study, the use of isoflurane-sufentanil in comparison with propofol-sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels. PMID- 20573634 TI - Impaired functional capacity is associated with all-cause mortality after major elective intra-abdominal surgery. AB - BACKGROUND: Studies of preoperative cardiopulmonary exercise testing (CPET) have shown that a reduced oxygen uptake at anaerobic threshold (AT) and elevated ventilatory equivalent for carbon dioxide (VE/VCO(2)) were associated with reduced short- and medium-term survival after major surgery. The aim of this study was to determine the relative values of these, and also clinical risk factors, in identifying patients at risk of death after major intra-abdominal, non-vascular surgery. METHODS: Patients aged >55 yr, undergoing elective colorectal resection, radical nephrectomy, or cystectomy between June 2004 and May 2009 had CPET during their routine pre-assessment clinic visit. We performed a retrospective analysis of known clinical risk factors and data from CPET to assess their relationship to all-cause mortality after surgery. RESULTS: Eight hundred and forty-seven patients underwent surgery, of whom 18 (2.1%) died. A clinical history of ischaemic heart disease (RR 3.1, 95% CI 1.3-7.7), a VE/VCO(2) >34 (RR 4.6, 95% CI 1.4-14.8), and an AT < or =10.9 ml kg(-1) min(-1) (RR 6.8, 95% CI 1.6-29.5) were all significant predictors of all-cause hospital and 90 day mortality. The effect of reduced AT was most pronounced in patients with no history of cardiac risk factors (RR 10.0, 95% CI 1.7-61.0). CONCLUSIONS: The routine measurement of AT and VE/VCO(2) using CPET for patients undergoing high risk surgery can accurately identify the majority of high-risk patients, while the use of clinical risk factors alone will only identify a relatively small proportion of at-risk patients. PMID- 20573635 TI - Duloxetine reduces morphine requirements after knee replacement surgery. AB - BACKGROUND: Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, has demonstrated efficacy in chronic pain conditions such as painful diabetic neuropathy and post-herpetic neuralgia. The objective of the study was to evaluate the efficacy of duloxetine in reducing morphine requirements in patients after knee replacement surgery. METHODS: Fifty patients received either two doses of oral duloxetine 60 mg (2 h before surgery and on first postoperative day) or placebo. All patients received patient-controlled analgesia with morphine for 48 h after operation. Pain and adverse effects were assessed at 0.5, 1, 2, 6, 12, 24, and 48 h after surgery on an 11-point numeric rating scale. RESULTS: Twenty-three patients in the duloxetine group and 24 patients in the placebo group completed the study. Morphine requirements during the 48 h after surgery were significantly lower in the duloxetine group [19.5 mg, standard deviation (sd) 14.5 mg] compared with the placebo group (30.3 mg, sd 18.1 mg) (P=0.017). There were no statistically significant differences between the groups in pain scores (at rest and on movement) or in adverse effects. CONCLUSIONS: Perioperative administration of duloxetine reduced postoperative morphine requirements during the first 48 h after knee replacement surgery, without significant adverse effects. PMID- 20573637 TI - Contemporary practices in postcardiac arrest syndrome: the role of mild therapeutic hypothermia. AB - Out-of-hospital cardiac arrest remains a major cause of mortality and morbidity despite progress in resuscitative practices. The number of survivors with severe neurological impairment at hospital discharge is similarly dismal. Recently, much attention has been directed toward the use of mild therapeutic hypothermia in the care of comatose survivors with postcardiac arrest syndrome. Recent research suggests mild hypothermia lowers mortality and improves neurological outcome after successful treatment of cardiac arrest. The current 2005 updated guidelines of International Liaison Committee on Resuscitation and European Resuscitation Council recommend the utilization of mild induced hypothermia in postresuscitation treatment. Hypothermia induction in order to avoid the pathophysiological mechanisms of euthermia and hyperthermia and subsequent complications are briefly discussed. Cooling methods, potential side effects and questions regarding implementation of therapeutic hypothermia recommendations in every day clinical practice and future investigation are also addressed. PMID- 20573636 TI - Efficacy of catheter ablation and surgical CryoMaze procedure in patients with long-lasting persistent atrial fibrillation and rheumatic heart disease: a randomized trial. AB - AIMS: Catheter ablation and surgical Maze procedure are effective in treating atrial fibrillation (AF) patients. However, there is no study that compares the effect of circumferential pulmonary vein isolation (CPVI) combined with substrate ablation after valvular surgery and the concomitant Maze procedure for the treatment of AF in patients with rheumatic heart disease (RHD). The aim of this study was to compare the effectiveness of CPVI combined with substrate modification and surgical Maze procedure using Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) system for the treatment of long-lasting persistent AF in patients with RHD. METHODS AND RESULTS: Between January 2006 and June 2008, 99 patients with long-lasting persistent AF and RHD were randomly assigned to undergo valvular operation and CPVI combined with substrate modification 6 months after the surgery (Group A, 49 patients) or valvualr operation and concomitant Maze procedure (Group B, 50 patients). The mean follow up periods were 15 +/- 5 and 20 +/- 8 months in Groups A and B, respectively. After one procedure, Group B had a significantly higher freedom from artial arrhythmias compared with Group A (82% in Group B vs. 55.2% in Group A, P < 0.001). Fifteen patients in Group A underwent a redo procedure. Six patients in Group B underwent catheter ablation and four were treated successfully. The cumulative rates of sinus rhythm were 71% in Group A and 88% in Group B (P < 0.001). CONCLUSION: The concomitant Cox Maze procedure using SICTRA is more effective than subsequent CPVI combined with substrate modification in treating patients with long-lasting persistent AF and RHD. PMID- 20573638 TI - Calculating sample size in trials using historical controls. AB - BACKGROUND: Makuch and Simon [Sample size considerations for non-randomised comparative studies. J Chronic Dis 1980; 33: 175-81.] developed a sample size formula for historical control trials. When assessing power, they assumed the true control treatment effect to be equal to the observed effect from the historical control group. Many researchers have pointed out that the Makuch-Simon approach does not preserve the nominal power and type I error when considering the uncertainty in the true historical control treatment effect. PURPOSE: To develop a sample size formula that properly accounts for the underlying randomness in the observations from the historical control group. METHODS: We reveal the extremely skewed nature in the distributions of power and type I error, obtained over all the random realizations of the historical control data. The skewness motivates us to derive a sample size formula that controls the percentiles, instead of the means, of the power and type I error. RESULTS: A closed-form sample size formula is developed to control arbitrary percentiles of power and type I error for historical control trials. A simulation study further demonstrates that this approach preserves the operational characteristics in a more realistic scenario where the population variances are unknown and replaced by sample variances. LIMITATIONS: The closed-form sample size formula is derived for continuous outcomes. The formula is more complicated for binary or survival time outcomes. CONCLUSIONS: We have derived a closed-form sample size formula that controls the percentiles instead of means of power and type I error in historical control trials, which have extremely skewed distributions over all the possible realizations of historical control data. PMID- 20573639 TI - Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group. AB - BACKGROUND: The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' PURPOSE: We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. METHODS: The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. RESULTS: The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. LIMITATIONS: The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. PMID- 20573640 TI - Early diffuse demyelinating lesion in the cervical spinal cord predicts a worse prognosis in relapsing-remitting multiple sclerosis. AB - OBJECTIVE: To study the long-term outcome and persistence of two patterns of cervical spinal cord abnormality in early relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients with a spinal cord MRI performed during the first 3 years of the disease, a control MRI 5 years later and who have been followed up at least 10 years were included. Patients were grouped according the T2 spinal cord MRI into: (A) nodular pattern, if one or more focal lesions were present; and (B) diffuse pattern, defined as a poorly demarcated high signal area. The end point was defined as the time to reach an Expanded Disability Status Score (EDSS) of 4.0. RESULTS: Twenty-five patients were included; 12 in group A and 13 in group B. Three patients in group A and 9 in group B reached EDSS 4, in a mean time of 11 years in group A and 7 years in group B (log rank 10.3, p = 0.001). Multivariate Cox regression analysis assessing the risk of EDSS 4.0 including sex, age, number of relapses in the first 2 years, number of T2 brain lesions and spinal cord pattern showed higher risk for the diffuse pattern (hazard ratio 7.2, 95% confidence interval 1.4-36.4). Control MRI showed the persistence of the diffuse pattern in all patients, and the development of diffuse pattern in two patients with basal nodular lesions. CONCLUSIONS: The diffuse abnormality in cervical spinal cord at the beginning of the disease is persistent and predicts a worse prognosis in RRMS patients. PMID- 20573641 TI - Double vision: an exploration of radiologists' and general practitioners' views on using picture archiving and communication systems (PACS). AB - This article explores the perspectives of two user groups, general practitioners (GPs) and consultant radiologists (CRs), on the rollout of picture archiving and communications systems (PACS) within acute trusts and eventually to primary care as part of the electronic patient record. Qualitative interviews were conducted with 16 CRs and 31 GPs. Analysis was carried out using a grounded theory approach. Radiologists expressed positive views about the implementation of PACS in secondary care, but were wary of GPs accessing radiological images. GPs expressed concerns about the added burdens that PACS might bring to primary care, but most felt that sharing images with patients could benefit doctor-patient communication and increase patient satisfaction. This study highlights both impediments and pathways to the implementation of PACS in primary care, and illustrates the importance of regarding PACS as socially embedded and users as culturally disparate. PMID- 20573642 TI - Understanding the work of medical transcriptionists in the production of medical records. AB - Efforts to improve healthcare by reducing medical errors often center on the accuracy of medical records. At the same time, the impact of new technologies such as speech recognition technology on the process of producing medical records has not been sufficiently examined. In this article we analyzed interview data from medical transcriptionists (MTs) describing how they do the work of transcription to produce accurate medical records from doctors' dictation. We found that medical transcriptionists rely on several types of skills that current speech recognition technology lacks. We conclude with a discussion of the implications of these findings for the design and implementation of SRT systems for the production of medical records and for how the work of MTs can help reduce medical errors. PMID- 20573643 TI - Chart documentation quality and its relationship to the validity of administrative data discharge records. AB - The validity of administrative data may be vulnerable to how well physicians document medical charts. The objective of this study is to determine the relationship between chart documentation quality and the validity of administrative data. The charts for patients who underwent carotid endarterectomy were re-abstracted and rated for the quality of documentation. Poorly and well documented charts were compared by patient, physician, and hospital variables, as well as on agreement between the administrative and re-abstracted data. Of the 2061 charts reviewed, 42.6 per cent were rated well documented. The proportion of charts well documented varied from 14.6 to 87.5 per cent across 17 hospitals, but did not vary significantly by patient characteristics. The kappa statistic was generally higher for well-documented charts than for poorly documented charts, but varied across comorbidities. In conclusion, poorly documented hospital charts tend to be translated into invalid administrative data, which reduces the communication of clinical information among healthcare providers. PMID- 20573644 TI - Agreement between structured checklists and Medicaid claims for preventive dental visits in primary care medical offices. AB - For program evaluation purposes, the feasibility of matching Medicaid claims with physician-completed structured checklists (encounter forms, EFs) was assessed in a pediatric office-based preventive dental program. We examined agreement on visits (weighted kappa) and predictors of a match between EFs and claims (multinomial logit model with practice-level clustering). In total, 34,171 matches occurred between 41,252 EFs and 40,909 claims, representing 82.8 per cent of EFs and 83.5 per cent of claims. Agreement on visits was 56 per cent (weighted kappa = 0.66). Pediatric practices provided the majority of visits (82.4%) and matches. Increasing age of child and residence in same county as the medical practice increased the likelihood of a match. Structured checklists can be combined with claims to better assess provision of preventive dental services in pediatric primary care. However, future research should examine strategies to improve the completion of structured checklists by primary care providers if data beyond claims are to be used for program evaluation. PMID- 20573645 TI - Facilitating stroke care planning through simulation modelling. AB - Stroke is a leading cause of death and long-term severe disability. A major difficulty facing stroke care provision in the UK is the lack of service integration between the many authorities, professionals and stakeholders involved in the process. The objective of this article is to describe a prototype model to support integrative planning for local stroke care services.The model maps the flow of care in the acute and community segments of the care pathway for stroke patients and allows exploring alternatives for care provision. Simulation modelling can help to develop an understanding of the systemic impact of service change and improve the design and targeting of future services. PMID- 20573646 TI - The public and the Internet: multifaceted drives for seeking health information. AB - The aim of this study was to gain insight into people's drives, or motives, for seeking health information on the Internet. A systematic literature review, restricted to handbooks and reviews, was conducted by searching the databases of various disciplines. Each drive was translated into the context of health information. Five drives were retrieved from the fields of psychology, mass communication, library and information science, and medical science: drives regarding the retrieval of knowledge, social contact or support, tempering uncertainty, entertainment, and self-actualization. Based on these results, three hypotheses were generated for future research: (1) drives are interconnected and may be present simultaneously in the process of seeking information; (2) they not only serve as antecedents for the need for information, but are present throughout the entire information-seeking process; (3) they are subject to change throughout the information-seeking process. Various drives play a role in the health information-seeking process. PMID- 20573647 TI - Telomere lengths in human oocytes, cleavage stage embryos and blastocysts. AB - Telomeres are repeated sequences that protect the ends of chromosomes and harbour DNA repair proteins. Telomeres shorten during each cell division in the absence of telomerase. When telomere length becomes critically short, cell senescence occurs. Telomere length therefore reflects both cellular ageing and capacity for division. We have measured telomere length in human germinal vesicle (GV) oocytes and preimplantation embryos, by quantitative fluorescence in situ hybridization (Q-FISH), providing baseline data towards our hypothesis that telomere length is a marker of embryo quality. The numbers of fluorescent foci suggest that extensive clustering of telomeres occurs in mature GV stage oocytes, and in preimplantation embryos. When calculating average telomere length by assuming that each signal presents one telomere, the calculated telomere length decreased from the oocyte to the cleavage stages, and increased between the cleavage stages and the blastocyst (11.12 versus 8.43 versus 12.22 kb, respectively, P < 0.001). Other methods of calculation, based upon expected maximum and minimum numbers of telomeres, confirm that telomere length in blastocysts is significantly longer than cleavage stages. Individual blastomeres within an embryo showed substantial variation in calculated average telomere length. This study implies that telomere length changes according to the stage of preimplantation embryo development. PMID- 20573648 TI - Repair of quadricuspid aortic valve by bicuspidization: a novel technique. AB - Quadricuspid aortic valve (QAV) is a rare congenital lesion, generally manifesting with valve regurgitation. Standard treatment involves valve replacement, though anecdotal cases of successful repair by means of valve tricuspidization have been reported. Here, the successful application of a repair technique previously unreported in the setting of QAV is described. PMID- 20573649 TI - Infectious erosion of aorta ascendens during vacuum-assisted therapy of mediastinitis. AB - Sternal wound infection is a potentially life-threatening complication after cardiac surgery. With the vacuum-assisted closure (VAC) system a relatively new treatment option is available, with encouraging results and few complications. However, fatal right ventricular rupture for mechanical reasons has been reported. We report the case of a 34-year-old patient with life-threatening bleeding due to infectious erosion of the aorta ascendens during VAC therapy of mediastinitis after cardiac surgery. To the best of our knowledge, this is the first reported case of infectious erosion (i.e. not VAC-related) of cardiovascular structures during running vacuum-assisted therapy. PMID- 20573650 TI - Prognostic classifications of lymph node involvement in lung cancer and current International Association for the Study of Lung Cancer descriptive classification in zones. AB - The lymphatic drainage of solid organ tumors crosses through the lymph nodes (LNs) whose tumoral involvement may still be considered as local disease. Concerning lung cancer, LN involvement may be intrapulmonary (N1), and mediastinal and/or extra-thoracic. More than 30 years ago, mediastinal involved LNs were all considered as N2, and outside the scope of surgery. In 1978, Naruke presented an original article entitled 'Lymph node mapping and curability at various levels of metastasis in resected lung cancer', demonstrating that N2 was not a contraindication to surgery in all patients. The map permitted to localize the favorable N2 on the lung cancer ipsilateral side of the mediastinum. Several maps ensued aiming to discriminate between right and left involvement (1983), and to distinguish N2 (ipsilateral) and N3 (contralateral) mediastinal LN involvement (1983, 1986). The last map (1997 regional LN classification) was recently replaced by a descriptive classification in anatomical zones. This new LN map of the TNM classification for lung cancer is a step toward using anatomical view points which might be the best way to better understand lung cancer lymphatic spread. Nowadays, the LNs are easily identified by current radiological imaging, and their resectability may be anticipated. Each LN chain may be removed by en bloc lymphadenectomy performed during radical lung resection, a safe procedure which seems to be more oncological based than sampling, and which avoids the source of discrepancies pointed out during the labeling of LN stations by surgeons. PMID- 20573651 TI - Perioperative outcomes in hybrid versus conventional surgical coronary artery revascularisation. AB - A best evidence topic was written on perioperative outcomes in hybrid coronary revascularisation according to a structured protocol. The question addressed was 'In patients with stable multivessel coronary artery disease, does the use of hybrid coronary revascularisation compared to conventional and off-pump coronary artery bypass grafting (CABG) reduce perioperative morbidity and mortality?' Six hundred and twenty-three papers were found in the literature search. From these results, six comparative studies and one review paper appeared to be relevant. The authors, journal, date and country of publication, patient group studied, study type, relevant results and weaknesses of these papers were compiled and tabulated. Critical appraisal ruled out three of the six comparative studies identified by the search. Therefore, the following papers constituted best evidence. de Canniere et al. reported a non-randomised retrospective comparison of staged hybrid revascularisation with conventional CABG, showing an association with shorter intensive care unit and total hospital stays, as well as shorter time to return to work. Kon et al. reported a non-randomised retrospective comparison of simultaneous hybrid revascularisation with off-pump CABG, showing that fewer blood transfusions were required in addition to shorter intensive care and hospital stays. Vassiliades et al. reported a non-randomised retrospective comparison of staged hybrid revascularisation with off-pump CABG, which failed to show a difference between 30-day major adverse cardiac events in the two patient groups. DeRose reviewed 13 published series of hybrid revascularisation cases, concluding that experienced centres should consider hybrid revascularisation as an appropriate alternative to conventional CABG for selected patients. In summary, these papers provide limited evidence of improved perioperative outcomes in both staged and simultaneous hybrid revascularisation compared to CABG. Weaknesses of the comparative studies include the lack of mid-term and long-term follow-up and the difficulty of generalising results from specialist units to general cardiac surgical practice. A large randomised control trial comparing hybrid revascularisation and coronary artery bypass with mid-term follow-up will be required to establish the clinical effectiveness of this procedure. PMID- 20573652 TI - Experimental extracorporeal membrane oxygenation reduces central venous pressure: an adjunct to control of venous hemorrhage? AB - BACKGROUND: Venoarterial ECMO has been utilized in trauma patients to improve oxygenation, particularly in the setting of pulmonary contusions and ARDS. We hypothesized that venoarterial ECMO could reduce the central venous pressure in the trauma scenario, thus, alleviating major venous hemorrhage. METHODS: Ten swine were cannulated for venoarterial ECMO. Central venous pressure, mean arterial pressure, portal vein pressure and portal vein flow were recorded at three different flow rates in both a hemodynamic normal state and a setting of increased central venous pressure and right ventricular load, mimicking acute lung injury. RESULTS: Venoarterial ECMO reduced the central venous pressure (CVP( sup)) from 9.4+/-0.8 to 7.3+/-0.7 mmHg (p<0.01) and increased the mean arterial pressure from 103+/-8 to 119+/-10 mmHg (p<0.01) in the normal hemodynamic state. In the state of increased right ventricular load, the CVP(sup) declined from 14.3+/-0.4 to 11.0+/-0.7mmHg (p<0.01) and the mean arterial pressure (MAP) increased from 66+/-6 to 113 +/-5 mmHg (p<0.01). CONCLUSION: Venoarterial ECMO reduces systemic venous pressure while maintaining or improving systemic perfusion in both a normal circulatory state and in the setting of increased right ventricular load associated with acute lung injury. ECMO may be a useful tool in reducing blood loss during major venous hemorrhage in both trauma and selected elective surgery. PMID- 20573653 TI - Superior venous drainage in the "LifeBox": a portable extracorporeal oxygenator with a self-expanding venous cannula. AB - BACKGROUND: In an experimental setting, the performance of the LifeBox, a new portable extracorporeal membrane oxygenator (ECMO) system suitable for patient transport, is presented. Standard rectilinear percutaneous cannulae are normally employed for this purpose, but have limited flow and pressure delivery due to their rigid structure. Therefore, we aimed to determine the potential for flow increase by using self-expanding venous cannulae. METHODS: Veno-arterial bypass was established in three pigs (40.6+/-5.1 kg). The venous line of the cardiopulmonary bypass was established by cannulation of the external jugular vein. The arterial side of the circulation was secured by cannulation of the common carotid artery. Two different venous cannulae (SmartCanula 18/36F 430mm and Biomedicus 19F) were examined for their functional integrity when used in conjunction with the centrifugal pump (500-3000 RPM) of the LifeBox system. RESULTS: At 1500, 2000, 2500, and 3000 RPM, the blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 19F rectilinear cannula achieved a blood flow of 0.93+/-0.14, 1.47+/-0.37, 1.9+/ 0.68, and 1.5+/-0.9 l/min, respectively, and the 18/36F self-expanding cannula achieved 1.1+/-0.1, 1.9+/-0.33, 2.8+/-0.39 and 3.66+/-0.52 l/min. However, when tested for venous line pressure, the standard venous cannula achieved -29+/ 10.7mmHg while the self-expanding cannula achieved -13.6 +/-4.3mmHg at 1500 RMP. As the RPM increased from 2500 to 3000, the venous line pressure accounted for 141.9+/-20 and -98+/-7.3mmHg for the 19F rectilinear cannula and -30.6+/-6.4 and 45+/-11.6mmHg for the self-expanding cannula. CONCLUSION: The self-expanding cannula exhibited superior venous drainage ability when compared to the performance of the standard rectilinear cannula with the use of the LifeBox. The flow rate achieved was approximately 40% greater than the standard drainage device, with a maximal pump flow recorded at 4.3l/min. PMID- 20573654 TI - Non-pulsatile circulation with axial-flow left ventricular assist device preserves neurocognitive function. AB - Concerns about the potential impact of the non-pulsatile circulation pattern generated by the new generation axial-flow left ventricular assist devices on neurocognitive function led us to evaluate a patient in whom a Jarvik 2000 pump was implanted. We assessed the patient's baseline neurocognitive function preoperatively as well as at 1-month and 6-month follow-up, using a comprehensive battery of neuropsychological tests. A slight improvement in circumscribed neurocognitive domains was noted, with no evidence of further decline at the end of a 6-month follow-up period. PMID- 20573655 TI - Benefit effect of naloxone in benzodiazepines intoxication: findings of a preliminary study. AB - BACKGROUND: Naloxone, as a low-priced and available drug, may be useful in improvement of signs and symptoms of benzodiazepines intoxication. The aim of this study was assessment of its effect on benzodiazepines poisoning. METHODS: In this clinical-trial study, patients with typical signs and symptoms of benzodiazepines poisoning, who were referred to a poisoning center in Tehran in 2008, were selected. After recording of patients' characteristics, supportive treatment was initiated and patients were randomly assigned to the case group with intravenous (IV) injection of two 0.4 mg naloxone ampules or to the control group. Their signs and symptoms were evaluated again 0.5 hour later. Each of diazepam, clonazepam and alperazolam drug group had 30 patients and lorazepam drug group had 26 patients, half of which patients in each drug group received naloxone. RESULTS: Most of the participants were female and the mean age was 28 years. There were no significant differences between case and control groups in age, sex, time of drug consumption, tablet counts, signs and symptoms and level of consciousness at the admission time in each drug types. After naloxone injection in case groups, all signs and symptoms significantly improved in all drug types in comparison to control groups except nystagmus. In addition, level of consciousness significantly improved in case groups in all drug types except lorazepam. CONCLUSION: Findings of the study showed that naloxone is effective in management of benzodiazepines poisoning. However, future clinical trials with greater sample size are recommended. PMID- 20573656 TI - Soft drinks and obesity in Latvia: a stakeholder analysis. AB - BACKGROUND: Childhood obesity is now firmly on the political agenda in western Europe but has received rather less attention in the eastern region of the European Union. This is a situation that cannot continue forever, especially in the light of evidence of the future social and economic cost of failure to act. METHODS: Semi-structured interviews with key stakeholders in Latvia were conducted in October 2004 to understand the Latvian response to childhood obesity and, specifically, to soft drink consumption as one of its key risk factors. Analysis was undertaken using the established principles of stakeholder analysis to assess the position and influence of the stakeholders on consumption of soft drink consumption within broader efforts to curb obesity in children. RESULTS: Twenty interviews were conducted and no one refused to be interviewed. Most stakeholders were concerned or convinced of the importance of restricting soft drinks consumption as part of initiatives to prevent childhood obesity. The most influential and supportive stakeholders were high school and primary school directors and parent groups. CONCLUSION: These findings help elucidate the actions of the Latvian government in November 2006 when it moved to ban certain foods and drinks from schools based on a concern for the adverse impact of additives on child health. The rapidity with which this poorly evidenced decision took place may have been supported by the unique context of an unstable government, nutrition leadership in dissolution, relatively weak industry influence and a surprisingly strong movement of teachers and parents. PMID- 20573657 TI - The 2009 Garrod lecture: the evolution of antimicrobial resistance: a Darwinian perspective. AB - Microbes have evolved over 3.5 billion years and are arguably the most adaptable organisms on earth. Restricted genetically by their inability to reproduce sexually, bacteria have acquired several additional mechanisms by which to exchange genetic material horizontally. Such mechanisms have allowed bacteria to inhabit some of the most inhospitable environments on earth. It is thus hardly surprising that when faced with a barrage of inimical chemicals (antibiotics) they have responded with an equal and opposite force. This article compares and contrasts the evolution of antimicrobial resistance to beta-lactam antibiotics over the last 70 years in two bacterial species, namely Staphylococcus aureus, a highly evolved human pathogen, and Pseudomonas aeruginosa, an opportunistic nosocomial pathogen. PMID- 20573659 TI - fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. AB - OBJECTIVES: To elucidate the pharmacokinetic/pharmacodynamic (PK/PD) index that predicts colistin efficacy against Acinetobacter baumannii in neutropenic murine thigh and lung infection models, and to determine the extent of the emergence of resistance in vivo to colistin. METHODS: PK/PD of colistin was studied in thigh and lung infection models against A. baumannii ATCC 19606 and two multidrug resistant clinical isolates (two of the three strains were colistin heteroresistant). Dose fractionation studies were conducted over a daily dose range of 1-160 mg/kg colistin sulphate. Bacterial burden in tissues was measured at 24 h. Non-linear least squares regression analyses were employed to determine the PK/PD index (fAUC/MIC, fC(max)/MIC or fT(>MIC)) best correlating with the efficacy of colistin in each model. Real-time population analysis profiles were conducted for tissue samples to monitor the emergence of resistance. RESULTS: The fAUC/MIC was the PK/PD index that correlated best with efficacy in both thigh (R(2) = 0.90) and lung (R(2) = 0.80) infection models. The fAUC/MIC targets required to achieve stasis and 1 log kill against the three strains were 1.89 7.41 and 6.98-13.6 in the thigh infection model, respectively, while the corresponding values were 1.57-6.52 and 8.18-42.1 in the lung infection model. Amplification of colistin-resistant subpopulations was revealed for all strains in both models after 24 h colistin treatment. CONCLUSIONS: This study indicates the importance of achieving adequate time-averaged exposure to colistin and defined target fAUC/MIC values for various magnitudes of kill. Amplification of resistant subpopulations indicates the importance of investigating rational combinations with colistin. The results will facilitate efforts to optimize colistin use in humans. PMID- 20573660 TI - Is peritoneal fluid a sanctuary site for HIV? PMID- 20573661 TI - Molecular and functional characterization of a novel efflux pump, AmvA, mediating antimicrobial and disinfectant resistance in Acinetobacter baumannii. AB - OBJECTIVES: Acinetobacter baumannii has emerged as an important nosocomial pathogen in hospitalized patients, and causes a multitude of infections with significant morbidity and mortality. The aim of this study was to elucidate the role of a novel efflux pump in A. baumannii. METHODS: The open reading frame ABAYE1518, annotated as a putative Methyl Viologen resistance protein in the genome of strain A. baumannii AYE, exhibits >50% similarity with members of the major facilitator superfamily (MFS) multidrug efflux pumps. The antimicrobial susceptibility profiles of Escherichia coli KAM32 cells carrying the putative efflux pump were monitored by broth dilution method. Different efflux pump inhibitors were used for fluorimetric efflux assays. The functions of the putative efflux pump were confirmed in A. baumannii by insertional inactivation and complementation. Its expression in clinical isolates was analysed by reverse transcriptase-PCR. RESULTS: E. coli cells carrying the pump had decreased susceptibility to some antibiotics, disinfectants, dyes and detergents, with enhanced efflux activity. The pump was inactivated in a clinical isolate of A. baumannii AC0037 and further characterization confirmed its role in antimicrobial resistance by active efflux. We found increased expression of the pump in clinical isolates that also exhibited elevated tolerance to antibacterial agents. CONCLUSIONS: This report describes the functions of a novel resistance determinant, a member of the MFS efflux pumps, for the first time in A. baumannii. PMID- 20573662 TI - The 23rd RSM Symposium on Cystic Fibrosis in Children and Adults. PMID- 20573663 TI - Development of a modern adult cystic fibrosis centre in Manchester. PMID- 20573665 TI - Patients with cystic fibrosis should not be intubated and ventilated. PMID- 20573664 TI - Patients with cystic fibrosis should be intubated and ventilated. PMID- 20573666 TI - Manifesting carriage of a Duchenne muscular dystrophy mutation: an unusual cause of impaired lung function in CF. PMID- 20573667 TI - Minimizing the toxicity of aminoglycosides in cystic fibrosis. PMID- 20573668 TI - Cystic fibrosis presenting with corneal perforation and crystalline lens extrusion. PMID- 20573669 TI - Multiple strains of non-tuberculous mycobacteria in a patient with cystic fibrosis. PMID- 20573670 TI - Ischaemic heart disease--a new issue in cystic fibrosis? PMID- 20573671 TI - Highlights of the North American Cystic Fibrosis Conference 2009. PMID- 20573672 TI - Cystic fibrosis papers of the year 2009. PMID- 20573673 TI - Predictive factors of difficult implantation procedure in cardiac resynchronization therapy. AB - AIMS: The usefulness of cardiac resynchronization therapy (CRT) in patients with congestive heart failure is offset by its long, user-dependent, and technical procedure. No studies have been published regarding factors related to CRT implantation procedure duration and X-ray exposure. Additionally, only a few studies have investigated the predictive factors of primary left ventricular (LV) lead implant failure. The aim of this prospective study was two-fold: (i) to evaluate the prevalence and predictive factors of prolonged CRT implantation procedure and (ii) to identify the predictive factors of primary LV lead implantation failure. METHODS AND RESULTS: Between November 2008 and September 2009, 128 consecutive patients underwent CRT implantation; of these, 22 patients (17.2%) were excluded because of CRT generator replacement. Population characteristics were a mean age of 69 +/- 10 years, 28.3% female, New York Heart Association class 3.2 +/- 0.3, LV ejection fraction (LVEF; 29 +/- 6%), and QRS width 146 +/- 23 ms. Cardiac resynchronization therapy implantation was attempted in 106 patients, and first LV lead implantation was obtained in 96 of 106 patients (90.5% primary success). Ten primary implantations failed (9.5%), due to unsuccessful LV lead implants. A second procedure was successfully attempted in six patients with a second more experienced operator (5.7%). Among the remaining four patients, one patient required a surgical epicardial LV lead implantation, and the implantation was not reattempted in the other three patients. The overall success rate of CRT system implantation was 96.2% (102 of 106 patients). Procedure parameters were as follows: LV threshold (1.4 +/- 0.9 V); LV wave amplitude (15 +/- 8 mV); LV impedance (874 +/- 215 ohm); median procedure time (skin to skin), 55 min (45-80); and median of procedure fluoroscopy time, 11 min (6.2-29). In 24 patients (22.6%), difficult procedures requiring >or=85 min of implantation duration occurred. By univariate analysis, predictive factors of difficult implantation were LV ejection fraction (25.6 +/- 6 vs. 30.2 +/- 8%; P = 0.02), LV end-diastolic diameter (72.4 +/- 11 vs. 66 +/- 11 mm; P = 0.01), LV end systolic diameter (LVESD; 62 +/- 12 vs. 56 +/- 12 mm, P = 0.04), and the operator's experience (very experienced operator vs. less experienced operator, P = 0.006). By multivariate analysis, only primary LV lead implantation failure, LVESD, and operator's experience were independently associated with difficult procedures. In this patient subset with primary LV lead implant failure (n = 10), the only independent predictive factor was the LV end-systolic volume (P = 0.03). CONCLUSION: In this study, the rate of difficult CRT device implantation procedures approached 25%. Both the degree of LV dysfunction and the operator's experience were independent predictors of surgical difficulties. Left ventricular end-systolic volume was the only independent predictor of primary LV lead implant failure. PMID- 20573674 TI - Rupture of an abdominal aortic aneurysm post EVAR: a rare presentation of retroperitoneal liposarcoma. AB - Endoleak is the classical cause of rupture of aneurysms previously treated by endovascular means. We report a rare case of a retroperitoneal liposarcoma (LIS) invading an abdominal aortic aneurysm (AAA), previously treated by endovascular repair (EVAR), causing rupture. Furthermore, a brief discussion of the diagnostic challenges posed by retroperitoneal tumors is presented with a closing note on their management. PMID- 20573675 TI - Gender differences and factors associated with treatment-seeking behaviour for infertility in Rwanda. AB - BACKGROUND: This study examines perceptions of infertility causes, treatment seeking behaviour and factors associated with seeking medical care in an urban infertile population in Rwanda, as well as the response of health providers. METHODS: Between November 2007 and May 2009 a hospital based survey was conducted among 312 women and 254 male partners in an infertile relationship. RESULTS: Infertility causes based on a medical diagnosis were mentioned by 24% of women and 17% of men. Male infertility awareness was low in both sexes with 28% of men and 10% of women reporting male-related causes. Seventy-four per cent of women and 22% of men had sought care for their infertility in the past. Seeking treatment in the formal medical sector was associated with higher income, being married and infertility duration of more than 5 years in both sexes. In women, higher education and being nulliparous and in men blaming oneself for the infertility was also associated with seeking formal medical care. Participants reported a wide array of treatments they received in the past, often including ineffective or even harmful interventions. CONCLUSION: Health authorities should invest in improving information, education and counselling on issues pertaining to causes and treatments of infertility, and in drawing up guidelines for the management of infertility at all levels of health care. PMID- 20573676 TI - Disclosure patterns of mode of conception among mothers and fathers-5-year follow up of the Copenhagen Multi-centre Psychosocial Infertility (COMPI) cohort. AB - BACKGROUND: Most studies on disclosure of mode of conception after fertility treatment have focused on donor insemination. We present a large, longitudinal cohort study of fertility patients who conceived through a variety of fertility treatments, including both non-donor and donor techniques. METHODS: A cohort of 2812 women and men (n = 1406 couples) received questionnaires when initiating fertility treatment and at 1-year and 5-year follow-ups. At the 5-year follow up, the response rate was 69.4% and 1036 of the responding participants had at least one child born after fertility treatment. Around 66% of the children were conceived with in vitro fertilization or intrauterine insemination with partners semen, 26% with intracytoplasmic sperm injection, 7% with donor gametes and <1% with other treatments. The parents were asked whether they already had or intended to disclose the conception method to the child and to others. We used logistic regression to identify determinants among women and men for disclosure. RESULTS: Most of the parents had disclosed or intended to disclose the mode of conception to the child, and almost everyone had disclosed to someone else. Not having used donor gametes was a significant determinant of disclosure both to the child and to other people among women and men. Having disclosed to other people was a significant predictor for having disclosed or intending to disclose to the child. Among women, low social class was a significant determinant of disclosure to the child. Among men, satisfaction with the medical treatment was a significant determinant of disclosure to other people. CONCLUSIONS: We found a large majority who had or intended to disclose to the child how he/she was conceived. Non-disclosure was significantly related to the use of donor gametes. PMID- 20573677 TI - A conditionally replicative adenovirus, CRAd-S-pK7, can target endometriosis with a cell-killing effect. AB - BACKGROUND: Novel therapeutic approaches for endometriosis based on molecular strategies may prove to be useful. Conditionally replicative adenoviruses (CRAds) are designed to exploit key differences between target and normal cells. The wild type adenovirus (Adwt) promoter can be replaced by tissue-specific promoters, allowing viral replication only in target cells. Viral infectivity can be enhanced by altering Ad tropism via fiber modification. We investigated whether CRAds can be used to target endometriosis and determined the most efficient transcriptional- and transductional-targeting strategy. METHODS: An in vitro study was carried out using human endometriotic cell lines, 11Z (epithelial) and 22B (stromal), normal human ovarian surface epithelial cell line (NOSE006) and primary human endometriosis cells. A total of 9 promoters and 12 Ad tropism modifications were screened by means of a luciferase reporter assay. From this screening data, three CRAds (CRAd-S-pK7, CRAd-S-RGD, CRAd-S-F5/3sigma1, all incorporating the survivin promoter but with different fiber modifications) were selected to perform experiments using Adwt and a replication-deficient virus as controls. CRAds were constructed using a plasmid recombination system. Viral binding capacity, rates of entry and DNA replication were evaluated by quantitative real-time PCR of viral genome copy. Cell-killing effects were determined by crystal violet staining and a cell viability assay for different concentrations of viral particles per cell. RESULTS: Comparison of promoters demonstrated that the survivin promoter exhibited the highest induction in both endometriotic cell lines. Among the fiber-modified viruses, the polylysine modification (pK7) showed the best infection enhancement. CRAd-S-pK7 was validated as the optimal CRAd to target endometriosis in terms of binding ability, entry kinetics, DNA replication and cell-killing effect. CRAd-S-pK7 also exhibited a high level of DNA replication in primary endometriosis cells. CONCLUSIONS: CRAd-S-pK7 has the best infection and cell-killing effect in the context of endometriosis. It could prove to be a useful novel method to target refractory cases of endometriosis. PMID- 20573679 TI - Ultra-conservative fertility-sparing strategy for bilateral borderline ovarian tumours: an 11-year follow-up. AB - BACKGROUND: This is a prospective long-term extension study of a randomized controlled trial aimed to assess the risk-benefit ratio of an ultra-conservative fertility-sparing approach in patients with bilateral borderline ovarian tumours (BOTs). METHODS: The experimental group (n = 15) was treated with an ultra conservative surgical approach consisting of bilateral cystectomy, whereas the control group (n = 17) received a less conservative surgery consisting of oophorectomy plus controlateral cystectomy alone. All patients received a complete laparoscopic staging followed by a fertility enhancement programme. Patients who completed childbearing were treated with a non-conservative standard treatment at the first recurrence. RESULTS: After a follow-up period of 128 (9 interquartile range (IQR); 115-150 range) and 132 (7 IQR; 117-152 range) months for the experimental and control groups, respectively (P = 0.25), the time to first baby-in-arm (P < 0.02) and the relative rate (RR) of baby-in-arm (8.05 [95% confidence interval (CI), 1.20-9.66; P < 0.01]) were significantly lower and higher, respectively, for the experimental compared with the control group. Although the time to first recurrence was significently (P < 0.01) shorter for the experimental group, in the regression analysis the difference did not reach the statistic significance (P = 0.14), and the RR of recurrence (1.23 [95% CI, 0.62-3.17; P = 0.41]) was not significant. Finally the number needed to treat for pregnancy was three, the number needed to harm for radical surgery was only two. CONCLUSIONS: The ultra-conservative fertility-sparing approach is more effective than the standard approach in terms of reproductive outcomes, but presents a higher oncological risk. PMID- 20573678 TI - Epidermal growth factor effects on marmoset monkey (Callithrix jacchus) oocyte in vitro maturation, IVF and embryo development are altered by gonadotrophin concentration during oocyte maturation. AB - BACKGROUND: This is the first study of the effect of epidermal growth factor (EGF) on marmoset monkey oocytes matured in vitro. METHODS: We have evaluated the effects of 10 ng/ml EGF in combination with 1 or 10 IU/ml of gonadotrophins (FSH/hCG 1:1 ratio) during in vitro maturation (IVM) of marmoset oocytes. Immature cumulus-oocyte complexes (COCs) were retrieved from ovarian antral follicles of unprimed monkeys. COCs from six animals (n= 268) used in this study were randomly distributed among four experimental groups: (A) 1 FSH +1 hCG; (B) 10 FSH +10 hCG; (C) 1 FSH +1 hCG + EGF; and (D) 10 FSH +10 hCG + EGF (where 1 and 10 are concentrations, IU/ml). After IVM, oocytes were fertilized in vitro and embryos were allowed to progress up to 87-88 h. RESULTS: the highest rate of total and radial cumulus expansion was observed in Group A, with the lowest in Group B (P < 0.05). Neither maturation nor fertilization rate were affected by gonadotrophin concentration or presence of EGF. Addition of EGF increased degeneration and decreased first cleavage rate, which was significantly lower in Group C than Group A (P < 0.005). Interestingly, in the EGF groups some embryos cleaved faster than without EGF. CONCLUSIONS: The effects of EGF are highly dependent on concentration of gonadotrophins present in IVM medium. EGF has a negative effect on oocytes in the presence of low gonadotrophins, but contrastingly partially protects oocytes from the negative effects of high gonadotrophins. We propose that these observed negative effects of EGF may suggest use of an inappropriate dose of growth factor. PMID- 20573680 TI - High prevalence of polycystic ovary syndrome in women born small for gestational age. AB - BACKGROUND: There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). METHODS: This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirao Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. RESULTS: The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. CONCLUSIONS: The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population. PMID- 20573681 TI - Seven novel DAX1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia. AB - CONTEXT: DAX1 (for dosage-sensitive sex reversal, adrenal hypoplasia congenital critical region on the X chromosome, gene 1; also called NROB1) mutations are responsible for adrenal failure and hypogonadotropic hypogonadism in patients with adrenal hypoplasia congenita (AHC), through a loss of trans-repression of SF 1 (for steroidogenic factor-1)-mediated StAR (for steroidogenic acute regulatory protein) and LHbeta transcriptional activities and a reduction of GnRH expression. The correlation of clinical features with genetic and functional alterations of the gene was investigated in detail in AHC patients. OBJECTIVE: The present study aimed at identifying DAX1 mutations in Chinese AHC patients and investigating the functional defects of detected novel mutations. PATIENTS AND METHODS: Nine patients with AHC were recruited from eight families. DAX1 mutations were screened, and the transcriptional activities of the identified mutations were assessed in vitro. RESULTS: DAX1 mutations were detected in all nine patients enrolled in the study, with eight different mutations. Among the latter, seven are novel mutations, including two missense (L262P and C368F), one nonsense (Q222X), and four frame-shift (637delC, 652_653delAC, 973delC, and 774_775insCC) mutations. The functional studies showed that the mutant DAX1 was impaired by nuclear localization, loss of trans-repression of StAR and LHbeta transcriptional activities, and reduction of GnRH expression. CONCLUSION: These findings provide insight into the molecular events by which DAX1 mutations influence the hypothalamus-pituitary-gonadal and hypothalamus-pituitary-adrenal axis and lead to AHC and hypogonadotropic hypogonadism. PMID- 20573682 TI - Evaluation of temperature rise and bonding strength in cements used for permanent head attachments in rats and mice. AB - In animal models, devices such as indwelling catheters and intracranial cannulae are often fixed on the skull to allow sampling or injection in the freely moving animal. The most commonly used method to fixate these devices is by embedding them in a 'helmet' of cement which is fixed to the skull with screws. Methylmethacrylate cement is commonly used for this purpose. The disadvantages of this cement are the high polymerization temperature, poor bonding to the bone and long hardening time. We have evaluated the use of glass ionomer cement, carboxylat cement and cyanoacrylic glue as alternative for methylmethacrylate cement. Temperature increase during polymerization of methylmethacrylate cement and glass ionomer cement was measured in the cement on the skull and in the brain of 14 rats in an acute model. In a chronic model, 52 rats and 91 mice were equipped with a 'helmet' of one of the cements. The glass ionomer 'helmets' were applied without or with pretreatment of the skull. The attachment of the cement to the skull was checked every day. After four weeks the bonding strengths of the cements were measured. The glass ionomer cement had less temperature increase during polymerization and good bonding capabilities when compared with methylmethacrylate cement. Mechanical pretreatment of the skull resulted in a significant increase in bonding strength of glass ionomer cement in mice and rats as compared with chemical pretreatment. Furthermore, glass ionomer cement had a shorter hardening time than methylmethacrylate cement, and when the glass ionomer cement was used in prepacked capsules, it was possible to apply the cement sterilely and easily. Cyanoacrylic glue had good bonding capabilities to the skull of mice and is also a good substitute for methylmethacrylate cement. PMID- 20573683 TI - Method comparison for 241Am emergency urine bioassay. AB - 241Am is one of the high-risk radionuclides that might be used in a terrorist attack. 241Am in urine bioassay can identify the contaminated individuals who need immediate medical intervention and decontamination. This paper compares three methods for the measurement of 241Am in urine, namely liquid scintillation counting (LSC), inductively coupled plasma mass spectrometry (ICP-MS) and gamma spectrometry (GS), at two levels, 20 and 2 Bq l(-1). All three methods satisfied the ANSI N13.30 radio-bioassay criteria for accuracy and repeatability. ICP-MS offered the best sensitivity and fastest sample turnaround; however, the ICP-MS system used in this work may not be available in many bioassay laboratories. LSC and GS are more commonly available instruments. GS requires minimal or no sample preparation, which makes it a good candidate method. Moreover, the sample throughput can be significantly improved if the GS and LSC methods are automated. PMID- 20573684 TI - Evaluation of H*(10) using the developed spherical type neutron dose monitor. AB - An instrument for evaluating the neutron ambient dose equivalent has been developed. It has the characteristic of uniform response to wide energy of neutrons. The monitor is four-layered spherically shaped, based on moderation and absorption of neutrons. Neutron dose can be evaluated from the linear combination of three specific responses of thermoluminescent dosimeters (TLDs), which are located at three depths in the moderator. TLDs were arranged between layers of two consecutive depths on 12 radial axes at even intervals so that the monitor is equally sensitive to all directions of neutrons. In order to verify the usefulness of dose evaluation by the monitor, irradiation experiments were conducted at the FRS, JAEA. The D2O-moderated 252Cf was used for the calibration of the monitor. Experiments were also conducted by using two neutron sources of 252Cf bare and 241Am-Be. As a result, the evaluated dose for each irradiation was obtained close to the actual irradiated dose. It was confirmed that the method of dose evaluation by the developed monitor can be applied to practical neutron fields where the distance of neutron source is unknown. PMID- 20573685 TI - Activation of the farnesoid X receptor provides protection against acetaminophen induced hepatic toxicity. AB - The nuclear receptor, farnesoid X receptor (FXR, NR1H4), is known to regulate cholesterol, bile acid, lipoprotein, and glucose metabolism. In the current study, we provide evidence to support a role for FXR in hepatoprotection from acetaminophen (APAP)-induced toxicity. Pharmacological activation of FXR induces the expression of several genes involved in phase II and phase III xenobiotic metabolism in wild-type, but not Fxr(-/-) mice. We used chromatin immunoprecipitation-based genome-wide response element analyses coupled with luciferase reporter assays to identify functional FXR response elements within promoters, introns, or intragenic regions of these genes. Consistent with the observed transcriptional changes, FXR gene dosage is positively correlated with the degree of protection from APAP-induced hepatotoxicity in vivo. Further, we demonstrate that pretreatment of wild-type mice with an FXR-specific agonist provides significant protection from APAP-induced hepatotoxicity. Based on these findings, we propose that FXR plays a role in hepatic xenobiotic metabolism and, when activated, provides hepatoprotection against toxins such as APAP. PMID- 20573686 TI - WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappaB pathways. AB - Although genetic evidence demonstrated a requirement for Wnt5a during cartilage development, little is known about the mechanisms underlying Wnt5a-regulated chondrocyte growth and differentiation. We therefore investigated the signaling pathways by which Wnt5a influences chondrogenesis and differentiation to hypertrophy. Wnt5a treatment of chondroprogenitor cells increased chondrocyte hypertrophy and was associated with an increase in nuclear factor of activated T cells (NFAT) and a decrease in nuclear factor-kappaB (NF-kappaB) activation. In contrast, Wnt5a inhibited chondrocyte hypertrophy. This inhibition of hypertrophy occurred with the reciprocal signaling activation, in that a decrease in NFAT and an increase in NF-kappaB activation was observed. Furthermore, the increase in chondroprogenitor cell differentiation with Wnt5a treatment was blocked by calmodulin kinase or NFAT loss of function. In addition, the repression of chondrocyte hypertrophy observed was abrogated by NF-kappaB loss of function. Activation of the NFAT pathway downstream of Wnt5a also negatively regulated NF kappaB activity, providing evidence of antagonism between these two pathways. Mechanistically, Wnt5a acts to increase chondrocyte differentiation at an early stage through calmodulin kinase /NFAT-dependent induction of Sox9. Conversely, Wnt5a represses chondrocyte hypertrophy via NF-kappaB-dependent inhibition of Runx2 expression. These data indicate that Wnt5a regulates chondrogenesis and chondrocyte hypertrophy in a stage-dependent manner through differential utilization of NFAT- and NF-kappaB-dependent signal transduction. PMID- 20573687 TI - Signaling from the secretory granule to the nucleus: Uhmk1 and PAM. AB - Neurons and endocrine cells package peptides in secretory granules (large dense core vesicles) for storage and stimulated release. Studies of peptidylglycine alpha-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain (CD) of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by U2AF homology motif kinase 1 (Uhmk1) and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble CD fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously overexpressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wild-type mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent. PMID- 20573688 TI - A novel isoform of microphthalmia-associated transcription factor inhibits IL-8 gene expression in human cervical stromal cells. AB - Cervical ripening during pregnancy is a profound change in cervix structure and function characterized by increases in the proinflammatory cytokine IL-8 and dissolution of the cervical extracellular matrix. Relatively little is known about the molecular mechanisms that underlie these events. Here, we report identification of a novel isoform of micropthalmia-associated transcription factor in human cervical stromal cells (MiTF-CX) that is down-regulated 12-fold during cervical ripening and that represses expression of IL-8. Ectopic expression of MiTF-CX in human cervical stromal cells resulted in substantial suppression of endogenous IL-8 mRNA and protein expression, whereas expression of dominant negative MiTF-CX mutants with impaired DNA binding resulted in dramatic increases in IL-8 production. Gel shift, reporter gene, and chromatin immunoprecipitation assays revealed one strong binding site (E-box (-397) CACATG( 391)) in the human IL-8 promoter that was crucial for mediating transcriptional repression by MiTF-CX. Moreover, we show that MiTF-CX expression in the cervix was itself positively autoregulated via two E-box motifs within a 2.1-kb promoter fragment. We therefore propose that maintenance of cervical competency during pregnancy is an active process maintained through suppression of IL-8 by the transcription factor MiTF-CX. During cervical ripening, loss of MiTF-CX would result in significant up-regulation of IL-8 mRNA and protein synthesis, thereby leading to recruitment and activation of leukocytes within the cervix and dissolution of the extracellular matrix. PMID- 20573691 TI - Meeting the needs of children who have parents with chronic inflammatory musculoskeletal diseases. PMID- 20573690 TI - Disease activity and severity in early inflammatory arthritis predict hand cortical bone loss. AB - OBJECTIVES: To determine the influence of disease-related variables on hand cortical bone loss in women with early inflammatory arthritis (IA), and whether hand cortical bone mass predicts subsequent joint damage. METHOD: Adults aged >= 16 years with recent onset of IA were recruited to the Norfolk Arthritis Register between 1990 and 1998, and followed prospectively. At baseline, patients had their joints examined for swelling and tenderness and had CRP and disease activity 28-joint assessment score (DAS-28) measured. Radiographs of the hands were performed in a subgroup of patients at Year 1 and at follow-up, which were assessed using digital X-ray radiogrammetry (DXR). They were also evaluated for the presence of erosions using Larsen's method. Linear mixed models were used to investigate whether disease-related factors predicted change in DXR-areal bone mineral density (BMD(a)). We also evaluated whether DXR-BMD(a) predicted the subsequent occurrence of erosive disease. RESULTS: Two hundred and four women, mean (s.d.) age 55.1 (14.0) years, were included. Median follow-up between radiographs was 4 years. The mean within-subject change in BMD(a) was 0.024 g/cm(2) equivalent to 1% decline per year. After adjustment for age, height and weight, compared with those within the lower tertile for CRP, those in the upper tertile had greater subsequent loss of bone. This was true also for DAS-28 and Larsen score. Among those without erosions on the initial radiograph (121), DXR BMD(a) at baseline did not predict the new occurrence of erosions. CONCLUSION: Increased disease activity and severity are associated with accelerated bone loss. However, lower BMD(a) did not predict the new occurrence of erosive disease. PMID- 20573692 TI - Women's experience of SLE-related fatigue: a focus group interview study. AB - OBJECTIVE: The aim of this study was to describe women's experience of SLE related fatigue, how they express the feeling of fatigue, impact on life and strategies developed to manage fatigue in daily living. METHOD: Seven, semi structured focus group discussions with 33 women were audio-taped, transcribed verbatim and analysed according to qualitative content analysis. RESULTS: Perceptions of SLE-related fatigue were sorted into four themes. Nature of Fatigue, involved the sensation, occurrence and character. Aspects Affected by Fatigue described emotions that arose together with fatigue as well as aspects of work, family life, social contacts and leisure activities that were affected by fatigue. Striving Towards Power and Control concluded the array of ways used to manage daily life and were categorized into the mental struggle, structure, restrict and provide. Factors Influencing the Perception of Fatigue described understanding from their surroundings and pain as strongly influencing the experience and perception of fatigue. CONCLUSION: SLE-related fatigue was portrayed as an overwhelming phenomenon with an unpredictable character, resulting in the feeling that fatigue dominates and controls most situations in life. The choice of strategies was described as a balance with implications for how fatigue limited a person's life. Health care professionals are advised to take a more active role to empower people with SLE to find their own balance as a way to achieve a feeling of being in control. PMID- 20573693 TI - Association between endothelial dysfunction and hyperuricaemia. AB - OBJECTIVE: We used high-resolution peripheral vascular ultrasound imaging to assess endothelial function in hyperuricaemic patients. METHODS: Hyperuricaemia was defined as a serum uric acid concentration of > 7.7 mg/dl in men or > 6.6 mg/dl in women. Measurements of endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation were performed in 46 hyperuricaemic patients and an equal number of healthy age- and gender-matched normal controls by high-resolution two-dimensional ultrasonographic imaging of the brachial artery. The serum levels of glucose, creatinine, alanine aminotransferase (ALT), lipid profiles and high-sensitivity CRP were measured for both the study groups. RESULTS: The serum uric acid levels averaged 9.24 (1.16) and 6.18 (0.99) mg/dl in the hyperuricaemic and control groups, respectively. Body weight and BMI were significantly higher in the hyperuricaemic group than in the control group. The serum levels of creatinine, ALT, triglyceride and high-sensitivity CRP were significantly different between the two groups. The FMD values were significantly lower in the hyperuricaemic patients than in the controls [4.45% (3.13%) vs 7.10% (2.48%); P < 0.001]. The FMD values were negatively associated with serum uric acid levels (r = -0.273; P = 0.009). Multivariate regression analysis showed that the presence of hyperuricaemia (beta = -0.384; P < 0.001) and body weight (beta = 0.215; P = 0.017) were independent determinants of low FMD values. CONCLUSION: Hyperuricaemia is associated with endothelial dysfunction. Decreased nitric oxide bioavailability may be the main reason. PMID- 20573695 TI - Opposite roles of DMRT1 and its W-linked paralogue, DM-W, in sexual dimorphism of Xenopus laevis: implications of a ZZ/ZW-type sex-determining system. AB - A Y-linked gene, DMY/dmrt1bY, in teleost fish medka and a Z-linked gene, DMRT1, in chicken are both required for male sex determination. We recently isolated a W linked gene, DM-W, as a paralogue of DMRT1 in Xenopus laevis, which has a ZZ/ZW type sex-determining system. The DNA-binding domain of DM-W shows high sequence identity with that of DMRT1, but DM-W has no significant sequence similarity with the transactivation domain of DMRT1. Here, we first show colocalization of DM-W and DMRT1 in the somatic cells surrounding primordial germ cells in ZW gonad during sex determination. We next examined characteristics of DM-W and DMRT1 as a transcription factor in vitro. DM-W and DMRT1 shared a DNA-binding sequence. Importantly, DM-W dose-dependently antagonized the transcriptional activity of DMRT1 on a DMRT1-driven luciferase reporter system in 293 cells. We also examined roles of DM-W or DMRT1 in gonadal formation. Some transgenic ZW tadpoles bearing a DM-W knockdown vector had gonads with a testicular structure, and two developed into frogs with testicular gonads. Ectopic DMRT1 induced primary testicular development in some ZW individuals. These observations indicated that DM-W and DMRT1 could have opposite functions in the sex determination. Our findings support a novel model for a ZZ/ZW-type system in which DM-W directs female sex as a sex-determining gene, by antagonizing DMRT1. Additionally, they suggest that DM W diverged from DMRT1 as a dominant-negative type gene, i.e. as a ;neofunctionalization' gene for the ZZ/ZW-type system. Finally, we discuss a conserved role of DMRT1 in testis formation during vertebrate evolution. PMID- 20573694 TI - Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium. AB - Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes - olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic precursors that express high levels of Sox2 and Ascl1. Precursors expressing high levels of Meis genes primarily reside in the lateral OE, whereas precursors expressing high levels of Sox2 and Ascl1 primarily reside in the medial OE. Fgf8 maintains these expression signatures and proliferative identities. Using electroporation in the wild-type embryonic OE in vitro as well as Fgf8, Sox2 and Ascl1 mutant mice in vivo, we found that Sox2 dose and Meis1 - independent of Pbx co-factors - regulate Ascl1 expression and the transition from lateral to medial precursor state. Thus, we have identified proliferative characteristics and a dose-dependent transcriptional network that define distinct OE precursors: medial precursors that are most probably transit amplifying neurogenic progenitors for ORNs, VRNs and GnRH neurons, and lateral precursors that include multi-potent self-renewing OE neural stem cells. PMID- 20573696 TI - hand2 and Dlx genes specify dorsal, intermediate and ventral domains within zebrafish pharyngeal arches. AB - The ventrally expressed secreted polypeptide endothelin1 (Edn1) patterns the skeleton derived from the first two pharyngeal arches into dorsal, intermediate and ventral domains. Edn1 activates expression of many genes, including hand2 and Dlx genes. We wanted to know how hand2/Dlx genes might generate distinct domain identities. Here, we show that differential expression of hand2 and Dlx genes delineates domain boundaries before and during cartilage morphogenesis. Knockdown of the broadly expressed genes dlx1a and dlx2a results in both dorsal and intermediate defects, whereas knockdown of three intermediate-domain restricted genes dlx3b, dlx4b and dlx5a results in intermediate-domain-specific defects. The ventrally expressed gene hand2 patterns ventral identity, in part by repressing dlx3b/4b/5a. The jaw joint is an intermediate-domain structure that expresses nkx3.2 and a more general joint marker, trps1. The jaw joint expression of trps1 and nkx3.2 requires dlx3b/4b/5a function, and expands in hand2 mutants. Both hand2 and dlx3b/4b/5a repress dorsal patterning markers. Collectively, our work indicates that the expression and function of hand2 and Dlx genes specify major patterning domains along the dorsoventral axis of zebrafish pharyngeal arches. PMID- 20573698 TI - Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. AB - A long noncoding RNA, Kcnq1ot1, regulates the expression of both ubiquitously and tissue-specific imprinted genes within the Kcnq1 domain. However, the functional sequences of the Kcnq1ot1 RNA that mediate lineage-specific imprinting are unknown. Here, we have generated a knockout mouse with a deletion encompassing an 890-bp silencing domain (Delta890) downstream of the Kcnq1ot1 promoter. Maternal transmission of the Delta890 allele has no effect on imprinting, whereas paternal inheritance of the deletion leads to selective relaxation of the imprinting of ubiquitously imprinted genes to a variable extent in a tissue-specific manner. Interestingly, the deletion affects DNA methylation at somatically acquired differentially methylated regions (DMRs), but does not affect the histone modifications of the ubiquitously imprinted genes. Importantly, we found that Kcnq1ot1 recruits Dnmt1 to somatic DMRs by interacting with Dnmt1, and that this interaction was significantly reduced in the Delta890 mice. Thus, the ubiquitous and placental-specific imprinting of genes within the Kcnq1 domain might be mediated by distinct mechanisms, and Kcnq1ot1 RNA might mediate the silencing of ubiquitously imprinted genes by maintaining allele-specific methylation through its interactions with Dnmt1. PMID- 20573699 TI - Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system. AB - Wiring of the nervous system is a multi-step process involving complex interactions of the growing fibre with its tissue environment and with neighbouring fibres. Nogo-A is a membrane protein enriched in the adult central nervous system (CNS) myelin, where it restricts the capacity of axons to grow and regenerate after injury. During development, Nogo-A is also expressed by neurons but its function in this cell type is poorly known. Here, we show that neutralization of neuronal Nogo-A or Nogo-A gene ablation (KO) leads to longer neurites, increased fasciculation, and decreased branching of cultured dorsal root ganglion neurons. The same effects are seen with antibodies against the Nogo receptor complex components NgR and Lingo1, or by blocking the downstream effector Rho kinase (ROCK). In the chicken embryo, in ovo injection of anti-Nogo A antibodies leads to aberrant innervation of the hindlimb. Genetic ablation of Nogo-A causes increased fasciculation and reduced branching of peripheral nerves in Nogo-A KO mouse embryos. Thus, Nogo-A is a developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. PMID- 20573697 TI - Negative control of Smad activity by ectodermin/Tif1gamma patterns the mammalian embryo. AB - The definition of embryonic potency and induction of specific cell fates are intimately linked to the tight control over TGFbeta signaling. Although extracellular regulation of ligand availability has received considerable attention in recent years, surprisingly little is known about the intracellular factors that negatively control Smad activity in mammalian tissues. By means of genetic ablation, we show that the Smad4 inhibitor ectodermin (Ecto, also known as Trim33 or Tif1gamma) is required to limit Nodal responsiveness in vivo. New phenotypes, which are linked to excessive Nodal activity, emerge from such a modified landscape of Smad responsiveness in both embryonic and extra-embryonic territories. In extra-embryonic endoderm, Ecto is required to confine expression of Nodal antagonists to the anterior visceral endoderm. In trophoblast cells, Ecto precisely doses Nodal activity, balancing stem cell self-renewal and differentiation. Epiblast-specific Ecto deficiency shifts mesoderm fates towards node/organizer fates, revealing the requirement of Smad inhibition for the precise allocation of cells along the primitive streak. This study unveils that intracellular negative control of Smad function by ectodermin/Tif1gamma is a crucial element in the cellular response to TGFbeta signals in mammalian tissues. PMID- 20573701 TI - PAR-1 promotes primary neurogenesis and asymmetric cell divisions via control of spindle orientation. AB - In both invertebrate and vertebrate embryonic central nervous systems, deep cells differentiate while superficial (ventricular) epithelial cells remain in a proliferative, stem cell state. The conserved polarity protein PAR-1, which is basolaterally localised in epithelia, promotes and is required for differentiating deep layer cell types, including ciliated cells and neurons. It has recently been shown that atypical protein kinase C (aPKC), which is apically enriched, inhibits neurogenesis and acts as a nuclear determinant, raising the question of how PAR-1 antagonises aPKC activity to promote neurogenesis. Here we show that PAR-1 stimulates the generation of deep cell progeny from the superficial epithelium of the neural plate and that these deep cells have a corresponding (i.e. deep cell) neuronal phenotype. We further show that gain- and loss-of-function of PAR-1 increase and decrease, respectively, the proportion of epithelial mitotic spindles with a vertical orientation, thereby respectively increasing and decreasing the number of cleavages that generate deep daughter cells. PAR-1 is therefore a crucial regulator of the balance between symmetric (two superficial daughters) and asymmetric (one superficial and one deep daughter) cell divisions. Vertebrate PAR-1 thus antagonises the anti-neurogenic influence of apical aPKC by physically partitioning cells away from it in vivo. PMID- 20573700 TI - Mib-Jag1-Notch signalling regulates patterning and structural roles of the notochord by controlling cell-fate decisions. AB - In the developing embryo, cell-cell signalling is necessary for tissue patterning and structural organization. During midline development, the notochord plays roles in the patterning of its surrounding tissues while forming the axial structure; however, how these patterning and structural roles are coordinated remains elusive. Here, we identify a mechanism by which Notch signalling regulates the patterning activities and structural integrity of the notochord. We found that Mind bomb (Mib) ubiquitylates Jagged 1 (Jag1) and is essential in the signal-emitting cells for Jag1 to activate Notch signalling. In zebrafish, loss- and gain-of-function analyses showed that Mib-Jag1-Notch signalling favours the development of non-vacuolated cells at the expense of vacuolated cells in the notochord. This leads to changes in the peri-notochordal basement membrane formation and patterning surrounding the muscle pioneer cells. These data reveal a previously unrecognized mechanism regulating the patterning and structural roles of the notochord by Mib-Jag1-Notch signalling-mediated cell-fate determination. PMID- 20573702 TI - Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. AB - Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, the trophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst derived stem cells and in vivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development. PMID- 20573703 TI - TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation. AB - Tuberous sclerosis complex human disease gene products TSC1 and TSC2 form a functional complex that negatively regulates target of rapamycin (TOR), an evolutionarily conserved kinase that plays a central role in cell growth and metabolism. Here, we describe a novel role of TSC1/2 in controlling stem cell maintenance. We show that in the Drosophila ovary, disruption of either the Tsc1 or Tsc2 gene in germline stem cells (GSCs) leads to precocious GSC differentiation and loss. The GSC loss can be rescued by treatment with TORC1 inhibitor rapamycin, or by eliminating S6K, a TORC1 downstream effecter, suggesting that precocious differentiation of Tsc1/2 mutant GSC is due to hyperactivation of TORC1. One well-studied mechanism for GSC maintenance is that BMP signals from the niche directly repress the expression of a differentiation promoting gene bag of marbles (bam) in GSCs. In Tsc1/2 mutant GSCs, BMP signalling activity is downregulated, but bam expression is still repressed. Moreover, Tsc1 bam double mutant GSCs could differentiate into early cystocytes, suggesting that TSC1/2 controls GSC differentiation via both BMP-Bam-dependent and -independent pathways. Taken together, these results suggest that TSC prevents precocious GSC differentiation by inhibiting TORC1 activity and subsequently differentiation-promoting programs. As TSC1/2-TORC1 signalling is highly conserved from Drosophila to mammals, it could have a similar role in controlling stem cell behaviour in mammals, including humans. PMID- 20573704 TI - The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons. AB - Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease. Here, we demonstrate elevated expression of the transcription factor orthodenticle homeobox 2 in A10 dopaminergic neurons of embryonic and adult mouse, primate and human midbrain. Overexpression of orthodenticle homeobox 2 using lentivirus increased levels of known A10 elevated genes, including neuropilin 1, neuropilin 2, slit2 and adenylyl cyclase activating peptide in both MN9D cells and ventral mesencephalic cultures, whereas knockdown of endogenous orthodenticle homeobox 2 levels via short hairpin RNA reduced expression of these genes in ventral mesencephalic cultures. Lack of orthodenticle homeobox 2 in the ventral mesencephalon of orthodenticle homeobox 2 conditional knockout mice caused a reduction of midbrain dopaminergic neurons and selective loss of A10 dopaminergic projections. Orthodenticle homeobox 2 overexpression protected dopaminergic neurons in ventral mesencephalic cultures from Parkinson's disease-relevant toxin, 1-methyl-4-phenylpyridinium, whereas downregulation of orthodenticle homeobox 2 using short hairpin RNA increased their susceptibility. These results show that orthodenticle homeobox 2 is important for establishing subgroup phenotypes of post-mitotic midbrain dopaminergic neurons and may alter neuronal vulnerability. PMID- 20573705 TI - Arabidopsis putative deacetylase AtSRT2 regulates basal defense by suppressing PAD4, EDS5 and SID2 expression. AB - The silent information regulator protein (Sir2) and its homologs are NAD(+) dependent deacetylase enzymes that play important roles in a variety of physiological processes. However, the functions of the Sir2 family in plants are poorly understood. Here, we report that Arabidopsis AtSRT2, a homolog of yeast Sir2, negatively regulates plant basal defense against the pathogen Pseudomonas syringae pv. tomato DC3000 (PstDC3000). In response to PstDC3000 infection, the expression of AtSRT2 was down-regulated in a salicylic acid (SA)-independent manner. In addition, knock-out of AtSRT2 (srt2) enhanced resistance against PstDC3000 and increased expression of pathogenesis-related gene 1 (PR1). Conversely, overexpression of AtSRT2 resulted in hypersusceptibility to PstDC3000 and impaired PR1 induction. Consistent with this phenotype, expression of PAD4, EDS5 and SID2, three essential genes in the SA biosynthesis pathway, were increased in the srt2 mutant and decreased in AtSRT2-overexpressing plants. Taken together, these results demonstrate that AtSRT2 is a negative regulator of basal defense, possibly by suppressing SA biosynthesis. PMID- 20573710 TI - Polio outbreak in Tajikistan is cause for alarm. PMID- 20573711 TI - Evaluation of evidence-based literature and formulation of recommendations for the clinical preventive guidelines for immigrants and refugees in Canada. AB - BACKGROUND: This article describes the evidence review and guideline development method developed for the Clinical Preventive Guidelines for Immigrants and Refugees in Canada by the Canadian Collaboration for Immigrant and Refugee Health Guideline Committee. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) best-practice framework was combined with the recently developed Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to produce evidence-based clinical guidelines for immigrants and refugees in Canada. RESULTS: A systematic approach was designed to produce the evidence reviews and apply the GRADE approach, including building on evidence from previous systematic reviews, searching for and comparing evidence between general and specific immigrant populations, and applying the GRADE criteria for making recommendations. This method was used for priority health conditions that had been selected by practitioners caring for immigrants and refugees in Canada. INTERPRETATION: This article outlines the 14-step method that was defined to standardize the guideline development process for each priority health condition. PMID- 20573712 TI - Shear bond strength of fibre-reinforced composite nets using two different adhesive systems. AB - The purpose of this study was to evaluate the effect of two different adhesive systems (Tetric Flow and Transbond XT) in combination with fibre-reinforced composites (FRC) net (Ever Stick) on the shear bond strength (SBS) of orthodontic brackets. Eighty bovine permanent mandibular incisors were randomly divided into four equal groups. Stainless steel maxillary central incisor brackets with a 0.018 inch slot (DB Leone) were bonded to the teeth using the two different adhesive systems. Fifty per cent of the brackets were bonded without and 50 per cent with a FRC net under the bracket base. After bonding, all samples were stored in distilled water at room temperature for 24 hours and subsequently tested for SBS. Analysis of variance indicated significant differences among the various groups. Brackets bonded with FRC nets under the base showed a significantly lower SBS than those bonded without nets (P < 0.05). Moreover, teeth bonded with Transbond XT showed a significantly higher SBS than the other groups. Additionally, significant differences in debond locations [adhesive remnant index (ARI) score] were found among the various groups. Transbond XT can successfully be used for direct bonding of FRC nets, thus improving their SBS values. PMID- 20573713 TI - Earth's earliest atmospheres. AB - Earth is the one known example of an inhabited planet and to current knowledge the likeliest site of the one known origin of life. Here we discuss the origin of Earth's atmosphere and ocean and some of the environmental conditions of the early Earth as they may relate to the origin of life. A key punctuating event in the narrative is the Moon-forming impact, partly because it made Earth for a short time absolutely uninhabitable, and partly because it sets the boundary conditions for Earth's subsequent evolution. If life began on Earth, as opposed to having migrated here, it would have done so after the Moon-forming impact. What took place before the Moon formed determined the bulk properties of the Earth and probably determined the overall compositions and sizes of its atmospheres and oceans. What took place afterward animated these materials. One interesting consequence of the Moon-forming impact is that the mantle is devolatized, so that the volatiles subsequently fell out in a kind of condensation sequence. This ensures that the volatiles were concentrated toward the surface so that, for example, the oceans were likely salty from the start. We also point out that an atmosphere generated by impact degassing would tend to have a composition reflective of the impacting bodies (rather than the mantle), and these are almost without exception strongly reducing and volatile-rich. A consequence is that, although CO- or methane-rich atmospheres are not necessarily stable as steady states, they are quite likely to have existed as long-lived transients, many times. With CO comes abundant chemical energy in a metastable package, and with methane comes hydrogen cyanide and ammonia as important albeit less abundant gases. PMID- 20573714 TI - The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. AB - A major surprise arising from genome-wide analyses has been the observation that the majority of the genome is transcribed, generating noncoding RNAs (ncRNAs). It is still an open question whether some or all of these ncRNAs constitute functional networks regulating gene transcriptional programs. However, in light of recent discoveries and given the diversity and flexibility of long ncRNAs and their abilities to nucleate molecular complexes and to form spatially compact arrays of complexes, it becomes likely that many or most ncRNAs act as sensors and integrators of a wide variety of regulated transcriptional responses and probably epigenetic events. Because many RNA-binding proteins, on binding RNAs, show distinct allosteric conformational alterations, we suggest that a ncRNA/RNA binding protein-based strategy, perhaps in concert with several other mechanistic strategies, serves to integrate transcriptional, as well as RNA processing, regulatory programs. PMID- 20573715 TI - Membrane-associated DNA transport machines. AB - DNA pumps play important roles in bacteria during cell division and during the transfer of genetic material by conjugation and transformation. The FtsK/SpoIIIE proteins carry out the translocation of double-stranded DNA to ensure complete chromosome segregation during cell division. In contrast, the complex molecular machines that mediate conjugation and genetic transformation drive the transport of single stranded DNA. The transformation machine also processes this internalized DNA and mediates its recombination with the resident chromosome during and after uptake, whereas the conjugation apparatus processes DNA before transfer. This article reviews these three types of DNA pumps, with attention to what is understood of their molecular mechanisms, their energetics and their cellular localizations. PMID- 20573716 TI - Self-avoidance and tiling: Mechanisms of dendrite and axon spacing. AB - The spatial pattern of branches within axonal or dendritic arbors and the relative arrangement of neighboring arbors with respect to one another impact a neuron's potential connectivity. Although arbors can adopt diverse branching patterns to suit their functions, evenly spread branches that avoid clumping or overlap are a common feature of many axonal and dendritic arbors. The degree of overlap between neighboring arbors innervating a surface is also characteristic within particular neuron types. The arbors of some populations of neurons innervate a target with a comprehensive and nonoverlapping "tiled" arrangement, whereas those of others show substantial territory overlap. This review focuses on cellular and molecular studies that have provided insight into the regulation of spatial arrangements of neurite branches within and between arbors. These studies have revealed principles that govern arbor arrangements in dendrites and axons in both vertebrates and invertebrates. Diverse molecular mechanisms controlling the spatial patterning of sister branches and neighboring arbors have begun to be elucidated. PMID- 20573717 TI - Paraspeckles. AB - Paraspeckles are a relatively new class of subnuclear bodies found in the interchromatin space of mammalian cells. They are RNA-protein structures formed by the interaction between a long nonprotein-coding RNA species, NEAT1/Men epsilon/beta, and members of the DBHS (Drosophila Behavior Human Splicing) family of proteins: P54NRB/NONO, PSPC1, and PSF/SFPQ. Paraspeckles are critical to the control of gene expression through the nuclear retention of RNA containing double stranded RNA regions that have been subject to adenosine-to-inosine editing. Through this mechanism paraspeckles and their components may ultimately have a role in controlling gene expression during many cellular processes including differentiation, viral infection, and stress responses. PMID- 20573718 TI - Constitutive androstane receptor -null mice are sensitive to the toxic effects of parathion: association with reduced cytochrome p450-mediated parathion metabolism [corrected]. AB - Constitutive androstane receptor [corrected](CAR) is activated by several chemicals and in turn regulates multiple detoxification genes. Our research demonstrates that parathion is one of the most potent, environmentally relevant CAR activators with an EC(50) of 1.43 microM. Therefore, animal studies were conducted to determine whether CAR was activated by parathion in vivo. Surprisingly, CAR-null mice, but not wild-type (WT) mice, showed significant parathion-induced toxicity. However, parathion did not induce Cyp2b expression, suggesting that parathion is not a CAR activator in vivo, presumably because of its short half-life. CAR expression is also associated with the expression of several drug-metabolizing cytochromes P450 (P450). CAR-null mice demonstrate lower expression of Cyp2b9, Cyp2b10, Cyp2c29, and Cyp3a11 primarily, but not exclusively in males. Therefore, we incubated microsomes from untreated WT and CAR-null mice with parathion in the presence of esterase inhibitors to determine whether CAR-null mice show perturbed P450-mediated parathion metabolism compared with that in WT mice. The metabolism of parathion to paraoxon and p-nitrophenol (PNP) was reduced in CAR-null mice with male CAR-null mice showing reduced production of both paraoxon and PNP, and female CAR-null mice showing reduced production of only PNP. Overall, the data indicate that CAR-null mice metabolize parathion slower than WT mice. These results provide a potential mechanism for increased sensitivity of individuals with lower CAR activity such as newborns to parathion and potentially other chemicals due to decreased metabolic capacity. PMID- 20573719 TI - AUTO-MUTE: web-based tools for predicting stability changes in proteins due to single amino acid replacements. AB - Utilizing cutting-edge supervised classification and regression algorithms, three web-based tools have been developed for predicting stability changes upon single residue substitutions in proteins with known native structures. Trained models classify independent mutant test sets with accuracies ranging from 87 to 94%. Attributes representing each mutant protein are based on a computational mutagenesis methodology relying on a four-body statistical potential, illustrating a novel integration of both energy-based and machine learning approaches. The servers are written in PHP and hosted on a Linux platform, and they can be freely accessed online along with detailed data sets, documentation and performance results at http://proteins.gmu.edu/automute. PMID- 20573720 TI - Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up. AB - Obesity induced by high-fat (HF) feeding is associated with low-grade inflammation in peripheral tissues that predisposes to insulin resistance. Recent evidence suggests the occurrence of a similar process in the hypothalamus, which favors weight gain through impairment of leptin and insulin signaling. In addition to its implications for obesity pathogenesis, this hypothesis suggests that centrally targeted antiinflammatory therapies may prove effective in prevention and treatment of this disorder. This article highlights molecular and cellular mechanisms by which hypothalamic inflammation predisposes to diet induced obesity. PMID- 20573722 TI - Palmitate affects insulin receptor phosphorylation and intracellular insulin signal in a pancreatic alpha-cell line. AB - This study investigated in a pancreatic alpha-cell line the effects of chronic exposure to palmitate on the insulin and IGF-I receptor (IGF-IR) and intracellular insulin pathways. alpha-TC1-6 cells were cultured in the presence or absence of palmitate (0.5 mmol/liter) up to 48 h. Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. Erk 44/42 and p38 phosphorylation (P) (MAPK pathway markers) were also measured. Because MAPK can regulate Pax6, a transcription factor that controls glucagon expression, paired box gene 6 (Pax6) and glucagon gene and protein expression were also measured. Basal glucagon secretion was increased and the inhibitory effect of acute insulin exposure reduced in alpha-TC1 cells cultured with palmitate. Insulin-stimulated insulin receptor phosphorylation was greatly reduced by exposure to palmitate. Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. In contrast, with IGF-IR and IRS-2-P, the basal levels (i.e. in the absence of insulin stimulation) were higher in cells cultured with palmitate. Similar data were obtained with Erk 44/42-P and p-38-P. Pax6 and glucagon gene and protein expression were higher in cells cultured with palmitate. In these cells cultured, specifics MAPKs inhibitors were able to reduce both Pax6 and glucagon gene and protein expression. These results indicate that alpha-cells exposed to palmitate show insulin resistance of the IRS-1/PI3K/Akt pathway that likely controls glucagon secretion. In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression. Our data support the hypothesis that the chronic elevation of fatty acids contribute to alpha-cell dysregulation frequently observed in type 2 diabetes. PMID- 20573721 TI - Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice and appear after thyroglobulin antibodies. AB - Hashimoto's thyroiditis, a common autoimmune disease, is associated with autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). TPO, unlike abundant and easily purified Tg, is rarely investigated as an autoantigen in animals. We asked whether antibodies (Abs) develop to both TPO and Tg in thyroiditis that is induced (C57BL/6 and DBA/1 mice) or arises spontaneously (NOD.H-2h4 mice). Screening for TPOAbs was performed by flow cytometry using mouse TPO-expressing eukaryotic cells. Sera were also tested for binding to purified mouse Tg and human TPO. The antibody data were compared with the extent of thyroiditis. Immunization with mouse TPO adenovirus broke self-tolerance to this protein in C57BL/6 mice, but thyroiditis was minimal and TgAbs were absent. In DBA/1 mice with extensive granulomatous thyroiditis induced by Tg immunization, TPOAbs were virtually absent despite high levels of TgAbs. In contrast, antibodies to mouse TPO, with minimal cross-reactivity with human TPO, arose spontaneously in older (7-12 months) NOD.H-2h4 mice. Unexpectedly, TgAbs preceded TPOAbs, a time course paralleled in relatives of probands with juvenile Hashimoto's thyroiditis. These findings demonstrate a novel aspect of murine and human thyroid autoimmunity, namely breaking B cell self-tolerance occurs first for Tg and subsequently for TPO. PMID- 20573723 TI - Knockdown of GABA(A) receptor signaling in GnRH neurons has minimal effects upon fertility. AB - The amino acid gamma-aminobutyric acid (GABA) is thought to play a key role in shaping the activity of the GnRH neurons throughout embryonic and postnatal life. However, the physiological roles of direct GABA inputs to GnRH neurons remain unknown. Using a Cre-LoxP strategy, we generated a targeted mouse line, in which all (98 +/- 1%) GnRH neurons had the gamma2-subunit of the GABA(A) receptor deleted. Electrophysiological recordings of GABA(A)-mediated postsynaptic currents from green fluorescent protein-tagged GnRH neurons with the gamma2 subunit knocked out (GnRH gamma2 KO) showed that the amplitude and frequency of GABA(A) postsynaptic currents were reduced by 70% (P < 0.01) and 77% (P < 0.05), respectively, and that the response to exogenous GABA was reduced by 90% (P < 0.01). Evaluation of male and female GnRH gamma2 KO mice revealed completely normal fecundity, estrous cycles, and puberty onset. Further investigation with gonadectomy and different steroid replacement regimens showed normal basal levels of LH in both sexes, and a normal estradiol-evoked positive feedback mechanism in females. However, the increment in LH after gonadectomy in GnRH gamma2 KO female mice was double that of controls (P < 0.05) and also more potently suppressed by 17-beta-estradiol (P < 0.05). A similar but nonsignificant trend was observed in GnRH gamma2 KO male mice. Together, these findings show that 70-90% reductions in the normal levels of GABA(A) receptor activity at the GnRH neuron appear to impact upon the estrogen negative feedback mechanism but are, nevertheless, compatible with normal fertility in mice. PMID- 20573724 TI - Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations. AB - Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T(4)) and triiodothyronine (T(3)), and brain T(3) levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T(3) by 48%, serum total T(4) by 21%, and whole-brain T(3) by 10% at P12. Fe deficiency reduced serum total T(3) by 43%, serum total T(4) by 67%, and whole brain T(3) by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels. PMID- 20573725 TI - Neurokinin B stimulates GnRH release in the male monkey (Macaca mulatta) and is colocalized with kisspeptin in the arcuate nucleus. AB - Human genetics indicate that kisspeptin and neurokinin B (NKB) signaling are necessary for generating pulsatile LH release and therefore for initiation of puberty and maintaining gonadal function. In the present study, male monkeys were employed to examine 1) whether activation of the NKB receptor (NK3R) is associated with GnRH release, and 2) hypothalamic localization of these peptides using immunofluorescence histochemistry. Agonadal juveniles, in which pituitary responsiveness to GnRH was heightened by GnRH priming, were employed to indirectly examine GnRH-releasing actions of NK3R and kisspeptin receptor agonists by tracking LH after their i.v. injection. Castrated adults were used for immunohistochemistry. Single i.v. injections of NKB or senktide (an NK3R agonist) elicited robust LH discharges that were abolished by GnRH receptor antagonism (acyline) confirming the ligands' hypothalamic action. Intermittent infusion of senktide (1-min pulse every hour for 4 h), in contrast to that of kisspeptin, failed to sustain pulsatile GnRH release. Repetitive senktide injections did not compromise the GnRH-releasing action of kisspeptin. NKB and kisspeptin were colocalized in perikarya of the arcuate nucleus and in axonal projections to the median eminence, confirming earlier findings in sheep. These results are consistent with the human genetics, and indicate that although brief activation of NK3R stimulates GnRH release, repetitive stimulation of this pathway, in contrast to that of kisspeptin receptor, fails to sustain pulsatile GnRH release. In addition, the data provide a platform for future elucidation of the interactions between NKB and kisspeptin that are required for generating pulsatile GnRH release in primates. PMID- 20573726 TI - A soluble activin receptor type IIb prevents the effects of androgen deprivation on body composition and bone health. AB - Androgen deprivation, a consequence of hypogonadism, certain cancer treatments, or normal aging in men, leads to loss of muscle mass, increased adiposity, and osteoporosis. In the present study, using a soluble chimeric form of activin receptor type IIB (ActRIIB) we sought to offset the adverse effects of androgen deprivation on muscle, adipose tissue, and bone. Castrated (ORX) or sham-operated (SHAM) mice received either TBS [vehicle-treated (VEH)] or systemic administration of ActRIIB-mFc, a soluble fusion protein comprised of a form of the extracellular domain of ActRIIB fused to a murine IgG2aFc subunit. In vivo body composition imaging demonstrated that ActRIIB-mFc treatment results in increased lean tissue mass of 23% in SHAM mice [19.02 +/- 0.42 g (VEH) versus 23.43 +/- 0.35 g (ActRIIB-mFc), P < 0.00001] and 26% in ORX mice [15.59 +/- 0.26 g (VEH) versus 19.78 +/- 0.26 g (ActRIIB-mFc), P < 0.00001]. Treatment also caused a decrease in adiposity of 30% in SHAM mice [5.03 +/- 0.48 g (VEH) versus 3.53 +/- 0.19 g (ActRIIB-mFc), NS] and 36% in ORX mice [7.12 +/- 0.53 g (VEH) versus 4.57 +/- 0.28 g (ActRIIB-mFc), P < 0.001]. These changes were also accompanied by altered serum levels of leptin, adiponectin, and insulin, as well as by prevention of steatosis (fatty liver) in ActRIIB-mFc-treated ORX mice. Finally, ActRIIB-mFc prevented loss of bone mass in ORX mice as assessed by whole body dual x-ray absorptiometry and micro-computed tomography of proximal tibias. The data demonstrate that treatment with ActRIIB-mFc restored muscle mass, adiposity, and bone quality to normal levels in a mouse model of androgen deprivation, thereby alleviating multiple adverse consequences of such therapy. PMID- 20573728 TI - Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. AB - Maternal food restriction is associated with the development of obesity in offspring. This study examined how maternal undernutrition in sheep affects the fetal hypothalamic glucocorticoid receptor (GR) and the appetite-regulating neuropeptides, proopiomelanocortin (POMC) and neuropeptide Y, which it regulates. In fetuses from ewes undernourished from -60 to +30 d around conception, there was increased histone H3K9 acetylation (1.63-fold) and marked hypomethylation (62% decrease) of the POMC gene promoter but no change in POMC expression. In the same group, acetylation of histone H3K9 associated with the hypothalamic GR gene was increased 1.60-fold and the GR promoter region was hypomethylated (53% decrease). In addition, there was a 4.7-fold increase in hypothalamic GR expression but no change in methylation of GR gene expression in the anterior pituitary or hippocampus. Interestingly, hypomethylation of both POMC and GR promoter markers in fetal hypothalami was also identified after maternal undernutrition from -60 to 0 d and -2 to +30 d. In comparison, the Oct4 gene, was hypermethylated in both control and underfed groups. Periconceptional undernutrition is therefore associated with marked epigenetic changes in hypothalamic genes. Increase in GR expression in the undernourished group may contribute to fetal programming of a predisposition to obesity, via altered GR regulation of POMC and neuropeptide Y. These epigenetic changes in GR and POMC in the hypothalamus may also predispose the offspring to altered regulation of food intake, energy expenditure, and glucose homeostasis later in life. PMID- 20573729 TI - CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells. AB - AIMS: Endothelial progenitor cells (EPCs) play a pivotal role in endothelial repair after artery injury. The chemokine receptor CXCR4 is a key modulator of the homing of EPCs to impaired artery and reendothelialization. In this study, we addressed the hypothesis that CXCR4 gene transfer could enhance the reendothelialization capacity of EPCs. METHODS AND RESULTS: In vitro, human EPCs were expanded and transduced with adenovirus serotype 5 encoding the human CXCR4 gene (Ad5/CXCR4). In vitro, CXCR4 gene transfer augmented EPC migration and enhanced EPC adhesion to endothelial cell monolayers. Adhesion assays under flow conditions showed that CXCR4 gene transfer increased the ability of EPCs to arrest on fibronectin. To determine whether CXCR4 gene transfer facilitated therapeutic reendothelialization, the effect of EPCs on in vivo reendothelialization was examined in nude mice subjected to carotid artery injury. Compared with the vehicle, transplantation of EPCs with or without gene transfer significantly accelerated in vivo reendothelialization; however, transplantation of EPCs transduced with Ad5/CXCR4 had a further enhanced effect compared with control EPCs containing EPCs transduced with an adenovirus encoding enhanced green fluorescent protein gene or non-transduced EPCs. We also found that phosphorylation of Janus kinase-2 (JAK-2), a CXCR4 downstream signalling target, was increased in EPCs transduced with Ad5/CXCR4. The enhanced in vitro function and in vivo reendothelialization capacity of EPCs by CXCR4 gene transfer were abolished by neutralizing antibodies against CXCR4 or/and JAK-2 inhibitor AG490. CONCLUSION: The present study demonstrates that CXCR4 gene transfer contributes to the enhanced in vivo reendothelialization capacity of EPCs. Up regulation of CXCR4 in human EPCs may become a novel therapeutic target for endothelial repair. PMID- 20573727 TI - Diet-induced obesity model: abnormal oocytes and persistent growth abnormalities in the offspring. AB - Associations between maternal obesity and adverse fetal outcomes are well documented, but the mechanisms involved are largely unknown. Most previous work has focused on postconceptional events, however, our laboratory has shown pre- and periconceptional aberrations in maternal glucose metabolism have adverse effects on oocytes and embryos that carry on to the fetus. To demonstrate effects of maternal obesity in the pre- and periconceptional periods, we compared reproductive tissues from diet-induced obese female mice to those of control mice. Ovaries were either stained for follicular apoptosis or dissected and evaluated for oocyte size and meiotic maturation. Mice were also mated and followed for reproductive outcomes including preimplantation embryonic IGF-I receptor (IGF-IR) immunostaining, midgestation fetal growth, and midgestational placental IGF receptor 2 (Igf2r) mRNA. Delivered pups were followed for growth and development of markers of metabolic syndrome. Compared with controls, obese mice had significantly more apoptotic ovarian follicles, smaller and fewer mature oocytes, decreased embryonic IGF-IR staining, smaller fetuses, increased placental Igf2r mRNA, and smaller pups. All weaned pups were fed a regular diet. At 13 wk pups delivered from obese mice were significantly larger, and these pups demonstrated glucose intolerance and increased cholesterol and body fat suggesting early development of a metabolic-type syndrome. Together, our findings suggest maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stage and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception. PMID- 20573730 TI - Altered degradation of extracellular matrix in myocardial remodelling: the growing role of cathepsins and cystatins. PMID- 20573731 TI - Nothing but natural: targeting natural IgM in ischaemia/reperfusion injury. PMID- 20573733 TI - Application of the CHALICE clinical prediction rule for intracranial injury in children outside the UK: impact on head CT rate. AB - OBJECTIVE: The children's head injury algorithm for the prediction of important clinical events (CHALICE) is one of the strongest clinical prediction rules for the management of children with head injuries. The authors set out to determine the impact of this rule on the proportion of head injured patients receiving a CT scan in a major Australian paediatric emergency department. DESIGN: Retrospective cohort study. SETTING: Tertiary paediatric hospital emergency department in Australia (67 000 patients/year). PATIENTS: All head injured patients presenting to the emergency department in 2004. MAIN OUTCOME MEASURES: Actual proportion of head injured patients receiving a CT scan compared with the proportion had the CHALICE algorithm been applied. RESULTS: There were 1091 head injuries of all severities during the study period. 18% of head injured patients had a Glasgow Coma Scale <15, 19% a CT scan and 1.4% neurosurgical intervention. Application of the CHALICE algorithm would result in 46% receiving a CT scan. 303 patients who fit CHALICE criteria did not have a CT scan. These patients were managed with admission for observation or discharge and head injury instructions. Only five of these (1.6% or 0.5% of total head injuries) received a CT scan on representation for ongoing symptoms, four of which showed abnormalities on CT scan. CONCLUSIONS: Application of the CHALICE rule to this non-UK dataset would double the proportion of CT scans, with an apparent small gain in delayed pick-up of CT abnormalities. The role of expectant observation in hospital or at home needs to be defined. PMID- 20573735 TI - Constipation in children: an epidemiological study in Sri Lanka using Rome III criteria. AB - Constipation is a common paediatric problem, but its prevalence in Asia is unknown. A cross-sectional survey using a previously validated, self-administered questionnaire was conducted in randomly selected children aged 10-16 years, in five randomly selected schools in Sri Lanka. Two schools were in Eastern Province, which has been affected by the separatist war. Constipation was defined using Rome III criteria. Of 2694 children included in the analysis, 416 (15.4%) had constipation. Symptoms independently associated with constipation were straining (71.6% vs 28.4% of controls), bleeding per rectum (14.2% vs 2.2%) and abdominal pain (55% vs 35.2%). The prevalence of constipation was significantly higher in those with a family history of constipation (49% vs 14.8%), living in a war affected area (18.1% vs 13.7%) and attending an urban school (16.7% vs 13.3%). In conclusion, chronic constipation is a significant problem affecting 15% of Sri Lankan school children and adolescents. PMID- 20573736 TI - European Medicines Agency withdrawal for sibutramine. PMID- 20573737 TI - The role of Google in children's health. PMID- 20573738 TI - Outcome of goal-directed non-invasive ventilation and mechanical insufflation/exsufflation in spinal muscular atrophy type I. AB - BACKGROUND: There are widely discrepant views on the respiratory management of infants with spinal muscular atrophy (SMA) type I. Typically, management is palliative. DESIGN: A descriptive study of interventions and investigations is reported that were offered to a cohort of 13 children with SMA type I referred to our centre. Interventions and investigations included sleep studies, provision of non-invasive positive pressure ventilation (NIPPV) for ventilatory support/dependency and for physiotherapy and the use of mechanical insufflation/exsufflation (MI-E). RESULTS: NIPPV was provided for the following indications: continuous positive airways pressure flow driver dependency (n=3), nocturnal hypoventilation (n=3), to enable successful extubation (n=2), in anticipation of respiratory decompensation (n=3), and oxygen dependency/decompensation (n=2). NIPPV and MI-E were used for successful protocol led extubations (n=9) but not non protocol-led successes (n=3). NIPPV was essential for discharge home in patients with ventilatory dependency (n=7) and was used for palliation of respiratory symptoms (n=4). Chest wall shape improved with NIPPV. The parents of children who died (n=5) were positive about the use of these techniques. CONCLUSION: NIPPV can be used to facilitate discharge home, and MI-E is helpful in this group. This symptom and goal-directed approach can be used to inform medical decision making and to help parents make informed choices about the appropriateness of respiratory interventions in SMA type I. PMID- 20573739 TI - Attitudes and practices of physicians regarding physician-assisted dying in minors. AB - OBJECTIVE: To investigate attitudes towards physician-assisted death in minors among all physicians involved in the treatment of children dying in Flanders, Belgium over an 18-month period, and how these are related to actual medical end of-life practices. DESIGN: Anonymous population-based postmortem physician survey. SETTING: Flanders, Belgium. PARTICIPANTS: Physicians signing death certificates of all patients aged 1-17 years who died between June 2007 and November 2008. MAIN OUTCOME MEASURES: Attitudes towards physician-assisted death in minors and actual end-of-life practices in the deaths concerned. RESULTS: 124 physicians for 70.5% of eligible cases (N=149) responded. 69% favour an extension of the Belgian law on euthanasia to include minors, 26.6% think this should be done by establishing clear age limits and 61% think parental consent is required before taking life-shortening decisions. Cluster analysis yielded a cluster (67.7% of physicians) accepting of, and a cluster (32.2% of physicians) reluctant towards physician-assisted death in minors. Controlling for physician specialty and patient characteristics, acceptant physicians were more likely to engage in practices with the intention of shortening a patient's life than were reluctant physicians. CONCLUSION: A majority of surveyed Flemish physicians appear to accept physician-assisted dying in children under certain circumstances and favour an amendment to the euthanasia law to include minors. The approach favoured is one of assessing decision-making capacity rather than setting arbitrary age limits. These stances, and their connection with actual end-of-life practices, may encourage policy-makers to develop guidelines for medical end-of life practices in minors that address specific challenges arising in this patient group. PMID- 20573740 TI - Risk of skin cancer after neonatal phototherapy: retrospective cohort study. AB - OBJECTIVE: To assess the risk of skin cancer in persons treated with neonatal phototherapy (NNPT) for jaundice. DESIGN: Retrospective cohort study. SETTING: Grampian Region, Scotland, UK. DATA SOURCE: Aberdeen Maternity and Neonatal Databank. NNPT exposure was abstracted from paper records spanning 1976-1990. Follow-up to 31 December 2006 by linkage to cancer registration and mortality records. MAIN OUTCOME MEASURES: Incidence ratios, standardised for age, sex, calendar period and socio-economic position. RESULTS: After excluding neonatal deaths (n=435), the cohort comprised 77,518 persons. 5868 Received NNPT, providing 138,000 person-years at risk (median follow-up, 24 years). Two cases of melanoma occurred in persons exposed to NNPT versus 16 cases in unexposed persons, yielding a standardised incidence ratio of 1.40 (95% CI, 0.17 to 5.04; p=0.834). No cases of squamous cell or basal cell carcinoma of skin were observed in exposed persons. CONCLUSIONS: Although there is no statistically significant evidence of an excess risk of skin cancer following NNPT, limited statistical power and follow-up duration mean it is not possible categorically to rule out an effect. However, taken in conjunction with the results of the only other study to investigate risk of melanoma following NNPT, evidence available so far does not suggest a major cause for concern. PMID- 20573741 TI - Fatness leads to inactivity, but inactivity does not lead to fatness: a longitudinal study in children (EarlyBird 45). AB - OBJECTIVE: To establish in children whether inactivity is the cause of fatness or fatness the cause of inactivity. DESIGN: A non-intervention prospective cohort study examining children annually from 7 to 10 years. Baseline versus change to follow-up associations were used to examine the direction of causality. SETTING: Plymouth, England. PARTICIPANTS: 202 children (53% boys, 25% overweight/obese) recruited from 40 Plymouth primary schools as part of the EarlyBird study. MAIN OUTCOME MEASURES: Physical activity (PA) was measured using Actigraph accelerometers. The children wore the accelerometers for 7 consecutive days at each annual time point. Two components of PA were analysed: the total volume of PA and the time spent at moderate and vigorous intensities. Body fat per cent (BF%) was measured annually by dual energy x ray absorptiometry. RESULTS: BF% was predictive of changes in PA over the following 3 years, but PA levels were not predictive of subsequent changes in BF% over the same follow-up period. Accordingly, a 10% higher BF% at age 7 years predicted a relative decrease in daily moderate and vigorous intensities of 4 min from age 7 to 10 years (r=-0.17, p=0.02), yet more PA at 7 years did not predict a relative decrease in BF% between 7 and 10 years (r=-0.01, p=0.8). CONCLUSIONS: Physical inactivity appears to be the result of fatness rather than its cause. This reverse causality may explain why attempts to tackle childhood obesity by promoting PA have been largely unsuccessful. PMID- 20573742 TI - What do research ethics committees say about applications to conduct research involving children? AB - OBJECTIVE: To identify issues raised by research ethics committees (RECs) in letters about applications to conduct research involving children. METHODS: Analysis of 80 provisional and unfavourable opinion decision letters written by RECs in response to applications to conduct research involving child participants. RESULTS: RECs were most likely to be concerned about issues relating to consent, recruitment, care and protection of participants, scientific design and confidentiality. RECs focused on children's status as "vulnerable". They sought to ensure that children would be protected, that appropriate written language would be used to communicate with children and that an appropriate person would give consent for children to participate. IMPLICATIONS: Researchers should be attentive to issues of potential vulnerability when preparing applications. REC letters may be improved by giving clear and explicit reasons for their opinions. PMID- 20573743 TI - Does infant gastro-oesophageal reflux really deserve medical attention? PMID- 20573745 TI - STEM image simulation by Bloch-wave method with layer-by-layer representation. AB - In a Bloch-wave-based STEM image simulation, a framework for calculating the cross section for any incoherent scattering process was formulated by Allen et al. [(2003) Lattice-resolution contrast from a focused coherent electron probe. Part I. Ultramicroscopy 96: 47-63; Part II. ibid. 96: 65-81]. They simulated the high-angle annular dark-field, back-scattered electron, electron energy-loss spectroscopy and energy-dispersive X-ray (EDX) STEM images from the inelastic scattering coefficients. Furthermore, a skilful approach for deriving the excitation amplitude and block diagonalization in the eigenvalue equation was employed to reduce computing time and memory. In the present work, I extended their scheme to a layer-by-layer representation for application to inhomogeneous crystals. Calculations for a multi-layer Si sample including a displaced layer were performed by multiplying Allen et al.'s block-diagonalized matrices. Electron intensities within the sample and EDX STEM images were calculated at various conditions. From the calculations, three-dimensional STEM analysis was considered. PMID- 20573744 TI - A stimulatory role for the La-related protein 4B in translation. AB - La-related proteins (LARPs) belong to an evolutionarily conserved family of factors with predicted roles in RNA metabolism. Here, we have analyzed the cellular interactions and function of LARP4B, a thus far uncharacterized member of the LARP family. We show that LARP4B is a cytosolic protein that accumulates upon arsenite treatment in cellular stress granules. Biochemical experiments further uncovered an interaction of LARP4B with the cytosolic poly(A) binding protein 1 (PABPC1) and the receptor for activated C Kinase (RACK1), a component of the 40S ribosomal subunit. Under physiological conditions, LARP4B co sedimented with polysomes in cellular extracts, suggesting a role in translation. In agreement with this notion, overexpression of LARP4B stimulated protein synthesis, whereas knockdown of the factor by RNA interference impaired translation of a large number of cellular mRNAs. In sum, we identified LARP4B as a stimulatory factor of translation. We speculate that LARP4B exerts its function by bridging mRNA factors of the 3' end with initiating ribosomes. PMID- 20573746 TI - Transmission electron microscopic observation of cells cultured on multiwalled carbon nanotube-coated sponges. AB - The cell structure and interface between cultured cells and a multiwalled carbon nanotube (MWCNT)-coated sponge (MWCNT-coated sponge) were observed by transmission electron microscopy (TEM). Moreover, the atomic structure of MWCNTs that entered the cells was also examined by means of high-resolution TEM (HRTEM). MWCNTs were observed in the cytoplasm, and a few MWCNTs were recognized in the cell nuclei. Those MWCNTs maintained their structure there. Subcellular organelles did not appear to be different from those on the collagen sponge despite the cellular uptake of MWCNTs. PMID- 20573747 TI - In-situ TEM studies of the sintering behavior of copper nanoparticles covered by biopolymer nanoskin. AB - Sintering behavior of copper nanoparticles with a protective layer of gelatin synthesized by wet-chemical process with an average diameter of 45 nm has been observed using in-situ transmission electron microscopy (TEM). Copper nanoparticles were sublimated without sintering at about 925 degrees C at 2.0 x 10(-)(5) Pa, and carbonized gelatin remained and retained the shape of the initial layer of nanoparticles. Copper nanoparticles were sintered without sublimation at about 250 degrees C with between 1.0 x 10(-)(4) and 6.0 x 10(-)(4) Pa of oxygen gas flow. It was found that the surface of the sintered copper was covered by a gelatin layer. PMID- 20573748 TI - Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. AB - OBJECTIVE: NEUROD1 is expressed in both developing and mature beta-cells. Studies in mice suggest that this basic helix-loop-helix transcription factor is critical in the development of endocrine cell lineage. Heterozygous mutations have previously been identified as a rare cause of maturity-onset diabetes of the young (MODY). We aimed to explore the potential contribution of NEUROD1 mutations in patients with permanent neonatal diabetes. RESEARCH DESIGN AND METHODS: We sequenced the NEUROD1 gene in 44 unrelated patients with permanent neonatal diabetes of unknown genetic etiology. RESULTS: Two homozygous mutations in NEUROD1 (c.427_ 428del and c.364dupG) were identified in two patients. Both mutations introduced a frameshift that would be predicted to generate a truncated protein completely lacking the activating domain. Both patients had permanent diabetes diagnosed in the first 2 months of life with no evidence of exocrine pancreatic dysfunction and a morphologically normal pancreas on abdominal imaging. In addition to diabetes, they had learning difficulties, severe cerebellar hypoplasia, profound sensorineural deafness, and visual impairment due to severe myopia and retinal dystrophy. CONCLUSIONS: We describe a novel clinical syndrome that results from homozygous loss of function mutations in NEUROD1. It is characterized by permanent neonatal diabetes and a consistent pattern of neurological abnormalities including cerebellar hypoplasia, learning difficulties, sensorineural deafness, and visual impairment. This syndrome highlights the critical role of NEUROD1 in both the development of the endocrine pancreas and the central nervous system in humans. PMID- 20573750 TI - The effects of fenofibric acid alone and with statins on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia. AB - OBJECTIVE: To compare fenofibric acid (FA) + statin to respective monotherapies on the prevalence of metabolic syndrome and its diagnostic components in patients with mixed dyslipidemia. RESEARCH DESIGN AND METHODS: Post hoc analysis of over 2,000 metabolic syndrome patients administered either FA + low- or moderate-dose statin; FA alone; or low-, moderate-, or high-dose statin alone. RESULTS: FA + low- or moderate-dose statin combination therapy reduced the presence of metabolic syndrome (35.7 or 35.9%, respectively) more than low-, moderate-, or high-dose statin monotherapy (15.5, 16.6, or 13.8%, respectively), mostly due to improvements in triglycerides and HDL cholesterol levels. Mean glucose levels slightly decreased with FA monotherapy, slightly increased with statin monotherapy, and were essentially unchanged with FA + statin. FA with or without statin also reduced non-HDL cholesterol, apolipoprotein B, total cholesterol, VLDL cholesterol, and high-sensitivity C-reactive protein. CONCLUSIONS: FA + statin in patients with mixed dyslipidemia reduces the prevalence of metabolic syndrome. PMID- 20573749 TI - Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance. AB - OBJECTIVE: Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS: While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS: Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS: These findings confirm that the insulin-resistant state has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. PMID- 20573751 TI - Maternal glucose tolerance in pregnancy affects fetal insulin sensitivity. AB - OBJECTIVE: Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or beta-cell function. RESEARCH DESIGN AND METHODS: In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin, and proinsulin concentrations in maternal blood at the 50-g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation and in venous cord blood (n = 248). The cord blood glucose-to-insulin ratio and proinsulin concentration were used as indicators of fetal insulin sensitivity and the proinsulin-to-insulin ratio was used as an indicator of fetal beta-cell function. RESULTS: Higher OGTT blood glucose levels were associated with significantly lower cord plasma glucose-to-insulin ratios (r = -0.31, P < 0.001) and higher proinsulin concentrations (r = 0.31, P < 0.001) but not with proinsulin-to-insulin ratios. In a comparison of gestational diabetic (n = 26) versus euglycemic pregnancy, cord blood glucose-to-insulin ratios were substantially lower (geometric mean 10.1 vs. 20.0 mg/dl/microU/ml; P < 0.001), whereas proinsulin concentrations were much higher (24.4 vs. 13.8 pmol/l; P < 0.001), despite similar cord blood glucose concentrations indicating adequate management of diabetes. The differences remained significant after controlling for prepregnancy and fetal adiposity, family history of diabetes, gestational age, and other potential confounders. Significant changes in the glucose-to insulin ratio and proinsulin concentration were also observed in obese (n = 31) mothers, but the differences became not statistically significant after adjustment for maternal glucose tolerance and fetal adiposity. CONCLUSIONS: Maternal glucose intolerance may impair fetal insulin sensitivity (but not beta cell function) and consequently "program" the susceptibility to type 2 diabetes. PMID- 20573752 TI - Postchallenge glucose, A1C, and fasting glucose as predictors of type 2 diabetes and cardiovascular disease: a 10-year prospective cohort study. AB - OBJECTIVE: A1C has been proposed as a new indicator for high risk of type 2 diabetes. The long-term predictive power and comparability of elevated A1C with the currently used high-risk indicators remain unclear. We assessed A1C, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) as predictors of type 2 diabetes and cardiovascular disease (CVD) at 10 years. RESEARCH DESIGN AND METHODS: This prospective population-based study of 593 inhabitants from northern Finland, born in 1935, was conducted between 1996 and 2008. An oral glucose tolerance test (OGTT) was conducted at baseline and follow-up, and A1C was determined at baseline. Those with a history of diabetes were excluded from the study. Elevated A1C was defined as 5.7-6.4%. Incident type 2 diabetes was confirmed by two OGTTs. Cardiovascular outcome was measured as incident CVD or CVD mortality. Multivariate log-binomial regression models were used to predict diabetes, CVD, and CVD mortality at 10 years. Receiver operating characteristic curves compared predictive values of A1C, IGT, and IFG. RESULTS: Incidence of diabetes during the follow-up was 17.1%. Two of three of the cases of newly diagnosed diabetes were predicted by a raise in >or=1 of the markers. Elevated A1C, IGT, or IFG preceded diabetes in 32.8, 40.6, and 21.9%, respectively. CVD was predicted by an intermediate and diabetic range of 2-h glucose but only by diabetic A1C levels in women. CONCLUSIONS: A1C predicted 10-year risk of type 2 diabetes at a range of A1C 5.7-6.4% but CVD only in women at A1C >or=6.5%. PMID- 20573753 TI - Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients. AB - OBJECTIVE: The mean amplitude of glycemic excursions (MAGE) is a significant determinant of overall metabolic control as well as increased risk for diabetes complications. Older individuals with type 2 diabetes are more likely to have moderate cognitive deficits and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for cognitive performance in diabetic patients, we evaluated whether the contributions of MAGE to cognitive status in older patients with type 2 diabetes were independent from the main markers of glycemic control, such as sustained chronic hyperglycemia (A1C), postprandial glycemia (PPG), and fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS: In 121 older patients with type 2 diabetes, 48-h continuous subcutaneous glucose monitoring (CSGM) were assessed. MAGE and PPG were evaluated during CSGM. The relationship of MAGE to performance on cognitive tests was assessed, with adjustment for age, glycemic control markers, and other determinants of cognitive status. The cognitive tests were a composite score of executive and attention functioning and the Mini Mental Status Examination (MMSE). RESULTS: MAGE was significantly correlated with MMSE (r = 0.83; P < 0.001) and with cognition composite score (r = 0.68; P < 0.001). Moreover, MAGE was associated with the MMSE (P < 0.001) and cognition composite score (P < 0.001) independently of age, sex, BMI, waist-to-hip (WHR) ratio, drug intake, physical activity, mean arterial blood pressure, FPG, PPG, and A1C. CONCLUSIONS: MAGE during a daily period was associated with an impairment of cognitive functioning independent of A1C, FPG, and PPG. The present data suggest that interventional trials in older patients with type 2 diabetes should target not only A1C, PPG, and FPG but also daily acute glucose swings. PMID- 20573754 TI - A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS). AB - OBJECTIVE: A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known. RESEARCH DESIGN AND METHODS: A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG). RESULTS: IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7-6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P < 0.01), acute insulin response (r = - 0.20 vs. - 0.09; P < 0.01), and waist circumference (r = 0.43 vs. 0.25; P < 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = - 0.40 vs. - 0.27; P < 0.01) and triglycerides (r = 0.30 vs. 0.08; P < 0.001). CONCLUSIONS: A1C 5.7-6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders. PMID- 20573755 TI - Effects of weight loss among metabolically healthy obese men and women. AB - OBJECTIVE: Weight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults. RESEARCH DESIGN AND METHODS: Participants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed. RESULTS: Body weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05). CONCLUSIONS: Lifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors. PMID- 20573756 TI - The expanding epidemics of HIV type 1 among men who have sex with men in low- and middle-income countries: diversity and consistency. AB - Men who have sex with men (MSM) have borne a disproportionate burden of human immunodeficiency virus (HIV) infection and remain a markedly underresourced population globally. To better describe HIV epidemics among MSM in low- and middle-income countries, the authors conducted a systematic review of published and unpublished literature available after January 1, 2000 (2000-2009). A total of 133 HIV prevalence studies from 50 countries met the search criteria. Data were used to develop an algorithmic approach to categorize these epidemics. The authors found that the HIV epidemic in low- and middle-income countries may be described using the following 4 scenarios: 1) settings where MSM are the predominant contributor to HIV cases; 2) settings where HIV transmission among MSM occurs in the context of epidemics driven by injection drug users; 3) settings where HIV transmission among MSM occurs in the context of well established HIV transmission among heterosexuals; and 4) settings where both sexual and parenteral modes contribute significantly to HIV transmission. The authors focused on Peru, Ukraine, Kenya, and Thailand to describe the diversity across and similarities between proposed epidemic scenarios. This scenario-based categorization of HIV epidemics among MSM may assist public health agencies and civil societies to develop and implement better-targeted HIV prevention programs and interventions. PMID- 20573757 TI - Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries. AB - The sensory neuropeptide calcitonin gene-related peptide (CGRP) plays a role in primary headaches, and CGRP receptor antagonists are effective in migraine treatment. CGRP is a potent vasodilator, raising the possibility that antagonism of its receptor could have cardiovascular effects. We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant (MK-0974) [N [(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2 oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)piperidine-1-carboxamide] on human isolated coronary arteries. Arteries with different internal diameters were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human alphaCGRP were greater in distal coronary arteries (i.d. 600-1000 microm; E(max) = 83 +/- 7%) than proximal coronary arteries (i.d. 2-3 mm; E(max) = 23 +/- 9%), coronary arteries from explanted hearts (i.d. 3-5 mm; E(max) = 11 +/- 3%), and coronary arterioles (i.d. 200-300 microm; E(max) = 15 +/- 7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pretreatment with telcagepant (10 nM to 1 microM) antagonized alphaCGRP-induced relaxation competitively in distal coronary arteries (pA(2) = 8.43 +/- 0.24) and proximal coronary arteries and coronary arterioles (1 microM telcagepant, giving pK(B) = 7.89 +/- 0.13 and 7.78 +/- 0.16, respectively). alphaCGRP significantly increased cAMP levels in distal, but not proximal, coronary arteries, and this was abolished by pretreatment with telcagepant. Immunohistochemistry revealed the expression and colocalization of the CGRP receptor elements calcitonin-like receptor and receptor activity-modifying protein 1 in the smooth muscle cells in the media layer of human coronary arteries. These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions. PMID- 20573758 TI - Nausea with a twist. PMID- 20573759 TI - Sample size calculations II. PMID- 20573761 TI - Endometriosis. PMID- 20573762 TI - Random measurement error and regression dilution bias. PMID- 20573763 TI - Radiosurgery for brain tumours. PMID- 20573764 TI - How to think like an ethicist. PMID- 20573765 TI - G8 leaders must seize their chance to tackle undernutrition. PMID- 20573766 TI - Would action on health inequalities have saved New Labour? PMID- 20573767 TI - Why medicine is overweight. Don't forget inconvenient truth of supplier induced demand. PMID- 20573774 TI - Pre-exposure to context affects learning strategy selection in mice. AB - The multiple memory systems hypothesis proposes that different types of learning strategies are mediated by distinct neural systems in the brain. Male and female mice were tested on a water plus-maze task that could be solved by either a place or response strategy. One group of mice was pre-exposed to the same context as training and testing (PTC) and the other group was pre-exposed to a different context (PDC). Our results show that the PTC condition biased mice to place strategy use in males, but this bias was dependent on the presence of ovarian hormones in females. PMID- 20573775 TI - Transactivation of cytosolic alanine aminotransferase gene promoter by p300 and c Myb. AB - Alanine aminotransferase (Alt) provides a molecular link between carbohydrate and amino acid metabolism. In the cell context, the predominant Alt isozyme is located in the cytosol. To gain insight into the transcriptional regulation of the cytosolic alt gene (calt), we cloned and characterized the calt promoter from gilthead sea bream (Sparus aurata). Transient transfection of sea bass larvae cells with deleted calt promoter constructs and electrophoretic mobility shift assays allowed us to identify p300 and c-Myb as new factors in the transcriptional regulation of calt expression. Transfection studies carried out with an acetylase-deficient mutant p300 (p300DY) revealed that the acetyltransferase activity of p300 is essential for the p300-mediated transcriptional activation of S. aurata calt. We had previously found up regulation of liver cAlt2, an alternatively spliced isoform of calt, under gluconeogenic conditions and in streptozotocin (STZ)-treated S. aurata. Quantitative RT-PCR assays showed that increased p300 and c-Myb mRNA levels in the liver of starved S. aurata contribute to enhancing the transcription of cAlt2. Consistently, the administration of insulin decreased both p300 and c-Myb expression. The mRNA levels of p300 and c-Myb were also analyzed in the liver of STZ-induced diabetic S. aurata. Treatment with STZ increased the expression of p300, whereas it decreased c-Myb. Our findings suggest an involvement of p300 and c-Myb in up-regulation of cAlt2 in the liver of S. aurata under starvation. In addition, these results provide evidence for a role of p300 in diabetes. PMID- 20573776 TI - Pseudogenization of the umami taste receptor gene Tas1r1 in the giant panda coincided with its dietary switch to bamboo. AB - Although it belongs to the order Carnivora, the giant panda is a vegetarian with 99% of its diet being bamboo. The draft genome sequence of the giant panda shows that its umami taste receptor gene Tas1r1 is a pseudogene, prompting the proposal that the loss of the umami perception explains why the giant panda is herbivorous. To test this hypothesis, we sequenced all six exons of Tas1r1 in another individual of the giant panda and five other carnivores. We found that the open reading frame (ORF) of Tas1r1 is intact in all these carnivores except the giant panda. The rate ratio (omega) of nonsynonymous to synonymous substitutions in Tas1r1 is significantly higher for the giant panda lineage than for other carnivore lineages. Based on the omega change and the observed number of ORF-disrupting substitutions, we estimated that the functional constraint on the giant panda Tas1r1 was relaxed ~ 4.2 Ma, with its 95% confidence interval between 1.3 and 10 Ma. Our estimate matches the approximate date of the giant panda's dietary switch inferred from fossil records. It is probable that the giant panda's decreased reliance on meat resulted in the dispensability of the umami taste, leading to Tas1r1 pseudogenization, which in turn reinforced its herbivorous life style because of the diminished attraction of returning to meat eating in the absence of Tas1r1. Nonetheless, additional factors are likely involved because herbivores such as cow and horse still retain an intact Tas1r1. PMID- 20573777 TI - Rapid sequence and expression divergence suggest selection for novel function in primate-specific KRAB-ZNF genes. AB - Recent segmental duplications (SDs), arising from duplication events that occurred within the past 35-40 My, have provided a major resource for the evolution of proteins with primate-specific functions. KRAB zinc finger (KRAB ZNF) transcription factor genes are overrepresented among genes contained within these recent human SDs. Here, we examine the structural and functional diversity of the 70 human KRAB-ZNF genes involved in the most recent primate SD events including genes that arose in the hominid lineage. Despite their recent advent, many parent-daughter KRAB-ZNF gene pairs display significant differences in zinc finger structure and sequence, expression, and splicing patterns, each of which could significantly alter the regulatory functions of the paralogous genes. Paralogs that emerged on the lineage to humans and chimpanzees have undergone more evolutionary changes per unit of time than genes already present in the common ancestor of rhesus macaques and great apes. Taken together, these data indicate that a substantial fraction of the recently evolved primate-specific KRAB-ZNF gene duplicates have acquired novel functions that may possibly define novel regulatory pathways and suggest an active ongoing selection for regulatory diversity in primates. PMID- 20573778 TI - The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET). AB - BACKGROUND: fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications. DESIGN: the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial. SETTING: HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia. SUBJECTS: all participants were > or =80 years of age and hypertensive. METHODS: participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture. RESULTS: there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498). CONCLUSIONS: despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate. PMID- 20573779 TI - Serum C-reactive protein as a biomarker for early detection of bacterial infection in the older patient. AB - BACKGROUND: although C-reactive protein (CRP) is widely used in younger populations, its value for diagnosing bacterial infection in older population is not well established. This study examined the usefulness of serum CRP level in the early detection of bacterial infection in older patients. METHODS: in a prospective cohort study, consecutive patients aged 70 years or over admitted to Aged Care wards were recruited. CRP levels were measured within 24 h of presentation, and their significance in predicting bacterial infections was analysed. The relationship between CRP and other clinical features of diagnosing bacterial infections (e.g. temperature, white cell count, neutrophil count, oxygen saturation, blood pressure and heart rate) was also examined. RESULTS: a total of 232 patients were recruited over a period of 3 months. CRP levels were 21.3 +/- 36.0 and 150.5 +/- 114.1 mg/l (mean +/- SD) in the non-infection and infection groups, respectively (P < 0.001). We found that the CRP cut-off value of 60 mg/l had the best combination of sensitivity and specificity. At this level, the sensitivity of diagnosing bacterial infection was 80.7%, specificity 96.0%, positive predictive value 91.9% and negative predictive value 89.8%. CRP and temperature had higher sensitivity and specificity than white cell count and neutrophil count in the diagnosis of infection. For every 1-mg/l increment in CRP, the risk of bacterial infection increases by 2.9%. CONCLUSION: CRP is a convenient and useful biomarker to predict early bacterial infection in older patients especially when other markers are atypical or not present. PMID- 20573780 TI - Allocation of nitrogen to chemical defence and plant functional traits is constrained by soil N. AB - Plants have evolved a vast array of defence mechanisms to avoid or minimize damage caused by herbivores and pathogens. The costs and benefits of defences are thought to vary with the availability of resources, herbivore pressure and plant functional traits. We investigated the resource (nitrogen) and growth cost of deploying cyanogenic glycosides in seedlings of Eucalyptus cladocalyx (Myrtaceae). To do this, we grew the plants under a range of soil N conditions, from levels that were limiting for growth to those that were saturating for growth, and we measured correlations between foliar chemical and performance attributes. Within each N treatment, we found evidence that, for every N invested in cyanogenic glycosides, additional N is added to the leaf. For the lowest N treatment, the additional N was less than one per cyanogenic glycoside, rising to some two Ns for the other treatments. The interaction between cyanogenic glycosides and both condensed tannins and total phenolic compounds was also examined, but we did not detect correlations between these compounds under constant leaf N concentrations. Finally, we did not detect a correlation between net assimilation rate, relative growth rate and cyanogenic glycoside concentrations under any soil N treatment. We conclude that the growth cost of cyanogenic glycosides was likely too low to detect and that it was offset to some degree by additional N that was allocated alongside the cyanogenic glycosides. PMID- 20573781 TI - Novel cationic lipids with enhanced gene delivery and antimicrobial activity. AB - Cationic lipids facilitate plasmid delivery, and some cationic sterol-based compounds have antimicrobial activity because of their amphiphilic character. These dual functions are relevant in the context of local ongoing infection during intrapulmonary gene transfer for cystic fibrosis. The transfection activities of two cationic lipids, dexamethasone spermine (DS) and disubstituted spermine (D(2)S), were tested as individual components and mixtures in bovine aortic endothelial cells and A549 cells. The results showed a 3- to 7-fold improvement in transgene expression for mixtures of DS with 20 to 40 mol% D(2)S. D(2)S and coformulations with DS, dioleoyl phosphatidylethanolamine, and DNA exhibited potent bactericidal activity against Escherichia coli MG1655, Bacillus subtilis, and Pseudomonas aeruginosa PAO1, which was maintained in bronchoalveolar lavage fluid. Complete bacterial killing was demonstrated at approximately 5 microM, including gene delivery formulations, with 2 orders of magnitude higher tolerance before eukaryotic membrane disruption (erythrocyte hemolysis). D(2)S also exhibited lipopolysaccharide (LPS) scavenging activity resulting in significant inhibition of LPS-mediated activation of human neutrophils with 85 and 65% lower interleukin-8 released at 12 and 24 h, respectively. Mixtures of DS and D(2)S can improve transfection activity over common lipofection reagents, and D(2)S has strong antimicrobial action suited for the suppression of bacterial-mediated inflammation. PMID- 20573782 TI - Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation. AB - The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function. PMID- 20573783 TI - Thyroid function and human reproductive health. AB - Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves' disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function. PMID- 20573784 TI - The vision of toxicity testing in the 21st century: moving from discussion to action. AB - Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of toxicity testing that were not addressed in the original NRC report. Here, we offer a summary of the main points raised by the commentators in tabular form, identify a number of common themes, and finish the series by providing our perspective on several key issues in charting the path forward to move from discussion to action. PMID- 20573785 TI - Differential effects of polychlorinated biphenyl congeners on serum thyroid hormone levels in rats. AB - Polychlorinated biphenyls (PCBs) are known to reduce serum thyroxine (T(4)) in rats, but the relative effects of individual PCB congeners on thyroid hormones are not known. Thus, male Sprague-Dawley rats were administered Aroclor 1254, Aroclor 1242 (4, 8, 16, or 32 mg/kg/day), PCB 95 (2,2',3,5',6 pentachlorobiphenyl), PCB 99 (2,2',4,4',5-pentachlorobiphenyl), PCB 118 (2,3',4,4',5-pentachlorobiphenyl) (2, 4, 8, or 16 mg/kg/day), PCB 126 (3,3'4,4',5 pentachlorobiphenyl) (2.5, 5, 10, 20, or 40 microg/kg/day), TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin) (0.14, 0.43, 1.3, or 3.9 microg/kg/day), or corn oil via oral gavage for 7 days. Rats were necropsied 24 h after the last dose. Serum thyroid hormone levels were evaluated by radioimmunoassay, and induction of hepatic Cyp1a (a TCDD-inducible protein) and Cyp2b (a phenobarbital [PB] inducible protein) activity was determined by ethoxyresorufin-O-deethylase and pentoxyresorufin-O-deethylase assays, respectively. Significant increases in Cyp1a activity occurred in response to PCBs, except PCB 95 and PCB 99. Aroclor 1254, PCB 99, and PCB 118 significantly induced Cyp2b activity. Serum total T(4) and free T(4) were dramatically reduced in response to each of the seven treatments in a dose-dependent manner. The marked T(4) reductions occurred in response to Aroclor 1254, PCB 99 (a PB-type congener), and PCB 118 (a mixed-type congener). In contrast, reductions in serum triiodothyronine (total and free) were variable and mild, and serum thyroid-stimulating hormone was not significantly affected by any of the compounds. These data indicate that the PB and mixed-type PCB congeners are more effective than the TCDD-type PCB congeners at reducing serum T(4). PMID- 20573786 TI - Mitochondrial dysfunction induced by different organochalchogens is mediated by thiol oxidation and is not dependent of the classical mitochondrial permeability transition pore opening. AB - Ebselen (Ebs) and diphenyl diselenide [(PhSe)(2)] readily oxidize thiol groups. Here we studied mitochondrial swelling changes in mitochondrial potential (Deltapsim), NAD(P)H oxidation, reactive oxygen species production, protein aggregate formation, and oxygen consumption as ending points of their in vitro toxicity. Specifically, we tested the hypothesis that organochalchogens toxicity could be associated with mitochondrial dysfunction via oxidation of vicinal thiol groups that are known to be involved in the regulation of mitochondrial permeability (Petronilli et al. J. Biol. Chem., 269; 16638; 1994). Furthermore, we investigated the possible mechanism(s) by which these organochalchogens could disrupt liver mitochondrial function. Ebs and (PhSe)(2) caused mitochondrial depolarization and swelling in a concentration-dependent manner. Furthermore, both organochalchogens caused rapid oxidation of the mitochondrial pyridine nucleotides (NAD(P)H) pool, likely reflecting the consequence and not the cause of increased mitochondrial permeability (Costantini, P., Chernyak, B. V., Petronilli, V., and Bernardi, P. (1996). Modulation of the mitochondrial permeability transition pore (PTP) by pyridine nucleotides and dithiol oxidation at two separate sites. J. Biol. Chem. 271, 6746-6751). The organochalchogens induced mitochondrial dysfunction was prevented by the reducing agent dithiothreitol (DTT). Ebs- and (PhSe)(2)-induced mitochondrial depolarization and swelling were unchanged by ruthenium red (4microM), butylated hydroxytoluene (2.5microM), or cyclosporine A (1microM). N-ethylmaleimide enhanced the organochalchogens-induced mitochondrial depolarization, without affecting the magnitude of the swelling response. In contrast, iodoacetic acid did not modify the effects of Ebs or (PhSe)(2) on the mitochondria. Additionally, Ebs and (PhSe)(2) decreased the basal 2' 7' dichlorofluorescin diacetate (H(2)-DCFDA) oxidation and oxygen consumption rate in state 3 and increased it during the state 4 of oxidative phosphorylation and induced the formation of protein aggregates, which were prevented by DTT. However, DTT failed to reverse the formation of protein aggregates, when it was added after a preincubation of liver mitochondria with Ebs or (PhSe)(2). Similarly, DTT did not reverse the Ebs- or (PhSe)(2)-induced Deltapsim collapse or swelling, when it was added after a preincubation period of mitochondria with chalcogenides. These results show that Ebs and (PhSe)(2) can effectively induce mitochondrial dysfunction and suggest that effects of these compounds are associated with mitochondrial thiol groups oxidation. The inability of cyclosporine A to reverse the Ebs- and (PhSe)(2) induced mitochondrial effects suggests that the redox-regulated mitochondrial permeability transition (MPT) pore was mechanistically regulated in a manner that is distinct from the classical MPT pore. PMID- 20573787 TI - Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. AB - BACKGROUND: The intake of selenium needed for optimal health has not been established. Selenoproteins perform the functions of selenium, and the selenium intake needed for their full expression is not known. OBJECTIVE: This study sought to determine the intake of selenium required to optimize plasma selenoprotein P (SEPP1) and to compare SEPP1 with other plasma selenium biomarkers. DESIGN: A 40-wk placebo-controlled, double-blind study of selenium repletion was carried out in 98 healthy Chinese subjects who had a daily dietary selenium intake of 14 micro g. Fourteen subjects each were assigned randomly to daily dose groups of 0, 21, 35, 55, 79, 102, and 125 micro g Se as l selenomethionine. Plasma glutathione peroxidase (GPX) activity, SEPP1, and selenium were measured. A biomarker was considered to be optimized when its value was not different from the mean value of the subjects receiving larger supplements. RESULTS: The SEPP1 concentration was optimized at 40 wk by the 35- micro g supplement, which indicated that 49 micro g/d could optimize it. GPX activity was optimized by 21 micro g (total ingestion: 35 micro g/d). The selenium concentration showed no tendency to become optimized. CONCLUSIONS: The present results indicate that SEPP1 concentration is the best plasma biomarker studied for assessing optimal expression of all selenoproteins, because its optimization required a larger intake of selenium than did GPX activity. On the basis of the selenium intake needed for SEPP1 optimization with adjustments for body weight and individual variation, ap 75 micro g Se/d as selenomethionine is postulated to allow full expression of selenoproteins in US residents. This trial was registered at clinicaltrials.gov as NCT00428649. PMID- 20573788 TI - Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion. AB - BACKGROUND: Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors. OBJECTIVE: We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences in the distributions of lipoprotein concentrations and sizes were associated with the hepatic fat fraction (HFF), VAT, or both. DESIGN: In a multiethnic group of 33 white, 33 African American, and 33 Hispanic obese adolescents with normal glucose tolerance, we measured VAT and HFF by using magnetic resonance imaging. Fasting lipoprotein particle number and size were measured by using nuclear magnetic resonance spectroscopy. To assess the association between VAT and HFF, we categorized VAT into tertiles. RESULTS: In each ethnic group, HFF values increased between successive tertiles of VAT. After multivariate adjustment and in comparison with the 2 other groups, African Americans showed lower triglyceride (P = 0.001) and higher HDL (P = 0.03) concentrations, lower concentrations of total (P = 0.007), large (P = 0.005), and medium (P lt 0.0001) VLDL, but higher concentrations of large HDL particles (P = 0.01) and larger HDL (P = 0.005). In multivariate linear models, independent of ethnicity, VAT was a significant predictor for large HDL (P = 0.003) and total small LDL (P = 0.001) concentrations, whereas HFF significantly predicted large VLDL (P = 0.03) concentrations. CONCLUSION: Liver fat accretion, independent of VAT, may play a role in the ethnic differences seen in large VLDL particles. This trial was registered at clinicaltrials.gov as NCT00536250. PMID- 20573789 TI - Comparison of leucine and dispensable amino acid kinetics between Indian women with low or normal body mass indexes during pregnancy. AB - BACKGROUND: Evidence suggests that in women with a normal to high body mass index (BMI; in kg/m(2)), the extra amino acids needed during pregnancy are met through reduced oxidation. It is not known whether a woman with a low BMI can make this adaptation successfully. OBJECTIVE: The objective was to measure and compare leucine kinetic parameters and alanine-nitrogen, glutamine amide-nitrogen, and glycine and cysteine fluxes in Indian women with a low and normal BMI in early and midpregnancy. DESIGN: Fasted- and fed-state kinetics were measured by infusing 1-[(13)C]leucine, [(2)H(2)]cysteine, [(2)H(2)]glycine, [5 (15)N]glutamine, and [(15)N]alanine in groups of 10 women with a low BMI (<18.5) and 10 women with a normal BMI (18.5-25) in the first and second trimesters of pregnancy. RESULTS: Leucine, glutamine, glycine, and cysteine fluxes were faster in women with a low BMI in both trimesters, but there was no difference in alanine flux between groups. This difference was explained in the first trimester by a higher proportion of fat-free mass in low-BMI women. Leucine oxidation and percentage of dietary leucine oxidized were higher in low-BMI women in both trimesters, but nonoxidative disposal was not different between groups. CONCLUSIONS: Although they use dietary protein less efficiently, low-BMI women maintain net protein synthesis at the same rate as do normal-BMI women and produce similar quantities of labile nitrogen for the de novo synthesis of other dispensable amino acids such as glycine and cysteine. The extra amino acids required for increased maternal protein synthesis during pregnancy are provided by an overall decrease in amino acid catabolism in women with normal or low BMI. PMID- 20573790 TI - Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States. AB - BACKGROUND: Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer. OBJECTIVE: The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged > or =60 y. DESIGN: Surplus sera were analyzed with the use of data from the National Health and Nutrition Examination Survey (NHANES) 2001 2002, a cross-sectional, nationally representative survey (n = 1121). RESULTS: UMFA was detected in 38% of the population, with a mean concentration of 4.4 +/- 0.6 nmol/L (median: 1.2+/- 0.2 nmol/L). The group with UMFA (UMFA+) had a significantly higher proportion of folic acid supplement users than did the group without UMFA (60% compared with 41%). UMFA+ men and women also had higher supplemental and total (food + supplements) folic acid intakes than did their counterparts without UMFA. Forty percent of the UMFA+ group was in the highest quartile of total folic acid intake, but total folic acid intake was only moderately related to UMFA concentrations (r(2) = 0.07). Serum folate concentrations were significantly higher in the UMFA+ group and were predictive of UMFA concentrations (r(2) = 0.15). Serum 5-methyltetrahydrofolate and vitamin B-12 concentrations were higher in the UMFA+ group, whereas there was no difference between the 2 UMFA groups in red blood cell folate, serum homocysteine, or methylmalonic acid concentrations. CONCLUSIONS: Approximately 40% of older adults in the United States have UMFA that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted. PMID- 20573791 TI - Folate bioavailability from breads and a meal assessed with a human stable isotope area under the curve and ileostomy model. AB - BACKGROUND: Recent data revealed differences in human absorption kinetics and metabolism between food folates and folic acid supplements and fortificant. OBJECTIVE: The objective was to determine folate bioavailability after ingestion of breads or a breakfast meal fortified with either 5-CH(3)-H(4) folate or folic acid by using a stable-isotope area under the curve (AUC) and ileostomy model. DESIGN: In a randomized crossover trial, healthy ileostomists (n = 8) ingested single doses of whole-meal bread that contained ap 450 nmol (200 micro g) of either (6S)-[(13)C(5)]5-CH(3)-H(4) folate or [(13)C(5)]folic acid or a breakfast meal that contained ap 450 nmol (200 micro g) [(13)C(5)]folic acid. We collected blood from the subjects during 12 h postdose for assessment of plasma kinetics. Nonabsorbed folate was assessed from labeled folate contents in stomal effluent 12 and 24 h postdose. RESULTS: The median (range) plasma AUC(0 rarr 12) (AUC from 0 to 12 h after ingested dose) of 66 nmol sdot h/L (34-84 nmol sdot h/L) after ingestion of bread that contained (6S)-[(13)C(5)]5-CH(3)-H(4) folate was significantly greater (P lt 0.001) than that after ingestion of [(13)C(5)]folic acid in fortified bread [28 nmol sdot h/L (15-38 nmol sdot h/L)] and a fortified breakfast meal [26 nmol sdot h/L (15-60 nmol sdot h/L)]. Both labeled doses resulted in increases of plasma [(13)C(5)]5-CH(3)-H(4) folate. However, the kinetic variables C(max) (maximum plasma concentration) and T(max) [time (min) of maximum plasma concentration] varied after ingestion of the different folate forms. The stomal folate content was lt 10% of the ingested dose and did not vary significantly after ingestion of test foods that contained (6S)-[(13)C(5)]5-CH(3) H(4) folate [median (range): 13 nmol (10-31 nmol)] or [(13)C(5)]folic acid [median (range): 25 nmol (8-42 nmol)] (P = 0.33). CONCLUSIONS: Our data confirm differences in plasma absorption kinetics for reduced folates and synthetic folic acid administered with the test foods. Stomal folate contents indicated almost complete bioavailability of labeled folate from the breads or breakfast meal. PMID- 20573792 TI - Delayed onset of lactogenesis among first-time mothers is related to maternal obesity and factors associated with ineffective breastfeeding. AB - BACKGROUND: Delayed onset of lactogenesis (OL) is most common in primiparas and increases the risk of excess neonatal weight loss, formula supplementation, and early weaning. OBJECTIVE: We examined variables associated with delayed OL among first-time mothers who delivered at term and initiated breastfeeding (n = 431). DESIGN: We conducted in-person interviews during pregnancy and at days 0, 3, and 7 postpartum and extracted obstetric and newborn information from medical records. We defined OL as delayed if it occurred after 72 h and used chi-square analysis to examine its association with potential risk factors across 6 dimensions: 1) prenatal characteristics, 2) maternal anthropometric characteristics, 3) labor and delivery experience, 4) newborn characteristics, 5) maternal postpartum factors, and 6) infant feeding variables. We examined independent associations by using multivariable logistic regression analysis. RESULTS: Median OL was 68.9 h postpartum; 44% of mothers experienced delayed OL. We observed significant bivariate associations between delayed OL and variables in all 6 dimensions (P < 0.05). In a multivariate model adjusted for prenatal feeding intentions, independent risk factors for delayed OL were maternal age > or =30 y, body mass index in the overweight or obese range, birth weight >3600 g, absence of nipple discomfort between 0-3 d postpartum, and infant failing to "breastfeed well" > or =2 times in the first 24 h. Postpartum edema was significant in an alternate model excluding body mass index (P < 0.05). CONCLUSIONS: The risk factors for delayed OL are multidimensional. Public health and obstetric and maternity care interventions are needed to address what has become an alarmingly common problem among primiparas. PMID- 20573793 TI - Effect of change in physical activity on body fatness over a 10-y period in the Doetinchem Cohort Study. AB - BACKGROUND: Obesity is related to many adverse health-related outcomes. OBJECTIVE: We investigated whether changes in physical activity were related to less gain in either body weight or waist circumference (WC). DESIGN: The association between prospectively assessed physical activity and either body weight or WC was examined in 4944 participants of the Doetinchem Study (men and women aged between 26 and 66 y at baseline). Information on physical activity (derived from a validated physical activity index), body weight, and WC, measured according to standardized procedures, was collected at baseline and at the 5- and 10-y follow-ups. RESULTS: Random mixed-effects models showed that a single measurement of physical activity was not clearly related to change in body weight and WC over a 5-y period. However, analyses of repeated measures showed that compared with those who maintained their activity level, those who increased their physical activity over a 5-y period had less gain in WC ( minus 0.35 cm; 95% CI: minus 0.65, minus 0.05 cm) and possibly in body weight ( minus 280 g; 95% CI: minus 620, 5 g). Most importantly, these effects were sustained (although not significantly) in the consecutive 5 y for WC ( minus 0.56 cm; 95% CI: minus 108, 0.04 cm) and for body weight ( minus 590 g; 95% CI: minus 1005, minus 130 g), which indicated that physical activity was truly a determinant of body size changes. CONCLUSIONS: An increase in physical activity was associated with a statistically significant lower gain in body weight and in WC, which was maintained during the following 5 y. These findings support the need for public health programs that promote physical activity. PMID- 20573794 TI - Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. AB - BACKGROUND: New food biomarkers are needed to objectively evaluate the effect of diet on health and to check adherence to dietary recommendations and healthy eating patterns. OBJECTIVE: We developed a strategy for food biomarker discovery, which combined nutritional intervention with metabolic phenotyping and biomarker validation in a large-scale epidemiologic study. DESIGN: We administered a standardized diet to 8 individuals and established a putative urinary biomarker of fruit consumption by using (1)H nuclear magnetic resonance (NMR) spectroscopic profiling. The origin of the biomarker was confirmed by using targeted NMR spectroscopy of various fruit. Excretion kinetics of the biomarker were measured. The biomarker was validated by using urinary NMR spectra from UK participants of the INTERMAP (International Collaborative Study of Macronutrients, Micronutrients, and Blood Pressure) (n = 499) in which citrus consumption was ascertained from four 24-h dietary recalls per person. Finally, dietary patterns of citrus consumers (n = 787) and nonconsumers (n = 1211) were compared. RESULTS: We identified proline betaine as a putative biomarker of citrus consumption. High concentrations were observed only in citrus fruit. Most proline betaine was excreted < or =14 h after a first-order excretion profile. Biomarker validation in the epidemiologic data showed a sensitivity of 86.3% for elevated proline betaine excretion in participants who reported citrus consumption and a specificity of 90.6% (P < 0.0001). In comparison with noncitrus consumers, citrus consumers had lower intakes of fats, lower urinary sodium-potassium ratios, and higher intakes of vegetable protein, fiber, and most micronutrients. CONCLUSION: The biomarker identification and validation strategy has the potential to identify biomarkers for healthier eating patterns associated with a reduced risk of major chronic diseases. The trials were registered at clinicaltrials.gov as NCT01102049 and NCT01102062. PMID- 20573795 TI - Gastrointestinal metabolism of a vegetable-oil emulsion in healthy subjects. AB - BACKGROUND: Given the growing prevalence of overweight and obesity, weight management strategies could be developed based on the effect of specific food ingredients on the gastrointestinal system to reduce food intake. OBJECTIVE: The aim of this study was to investigate the mechanisms by which a vegetable-oil emulsion may exert its effect on satiety by applying a multilumen tube to investigate digestion and absorption of lipids in the stomach and proximal jejunum. DESIGN: We gave 16 healthy, normal-weight subjects (in a double-blind, placebo-controlled crossover design) a test product (yogurt with a vegetable-oil emulsion) or an equal-calorie control by intragastric administration on 2 separate occasions. Gastric and intestinal samples were collected from the proximal jejunum during 180 min. RESULTS: We observed almost double amounts (P < 0.05) of total lipids, mainly as free fatty acids, from the test product (450 +/- 119 mg) in the proximal jejunum compared with amounts of total lipids from the control product (230 +/- 50 mg), and an over-time difference of free fatty acid concentrations was observed between the products (P < 0.05). To our knowledge, a novel and unexpected finding was the appearance of needle-shaped crystals in the jejunal samples that originated from the vegetable-oil emulsion and consisted of saturated fatty acids. Crystals were only rarely seen in the control samples. CONCLUSION: The higher amount of lipids in the proximal jejunum and the recovery of crystals in the intestinal samples after test-product infusion provide a plausible physiologic explanation for the ileal brake mechanism that leads to the increased satiety observed for this test product. PMID- 20573796 TI - Combining or not combining published results in the presence of heterogeneity? PMID- 20573797 TI - Carbohydrate nutrition and inflammatory disease mortality in older adults. AB - BACKGROUND: Several studies suggest that carbohydrate nutrition is related to oxidative stress and inflammatory markers. OBJECTIVE: We examined whether dietary glycemic index (GI), dietary fiber, and carbohydrate-containing food groups were associated with the mortality attributable to noncardiovascular, noncancer inflammatory disease in an older Australian cohort. DESIGN: Analysis included 1490 postmenopausal women and 1245 men aged ge 49 y at baseline (1992-1994) from a population-based cohort who completed a validated food-frequency questionnaire. Cox proportional hazards ratios were calculated both for death from diseases in which inflammation or oxidative stress was a predominant contributor and for cardiovascular mortality. RESULTS: Over a 13-y period, 84 women and 86 men died of inflammatory diseases. Women in the highest GI tertile had a 2.9-fold increased risk of inflammatory death compared with women in the lowest GI tertile [multivariate hazard ratio in energy-adjusted tertile 3 (tertile 1 as reference): 2.89; 95% CI: 1.52, 5.51; P for trend: 0.0006, adjusted for age, smoking, diabetes, and alcohol and fiber consumption]. Increasing intakes of foods high in refined sugars or refined starches (P = 0.04) and decreasing intakes of bread and cereals (P = 0.008) or vegetables other than potatoes (P = 0.007) also independently predicted a greater risk, with subjects' GI partly explaining these associations. In men, only an increased consumption of fruit fiber (P = 0.005) and fruit (P = 0.04) conferred an independent decrease in risk of inflammatory death. No associations were observed with cardiovascular mortality. CONCLUSION: These data provide new epidemiologic evidence of a potentially important link between GI and inflammatory disease mortality among older women. PMID- 20573798 TI - Dietary fat intake and subsequent weight change in adults. PMID- 20573800 TI - Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study. AB - BACKGROUND: Information on the micronutrient quality of alternative weight-loss diets is limited, despite the significant public health relevance. OBJECTIVE: Micronutrient intake was compared between overweight or obese women randomly assigned to 4 popular diets that varied primarily in macronutrient distribution. DESIGN: Dietary data were collected from women in the Atkins (n = 73), Zone (n = 73), LEARN (Lifestyle, Exercise, Attitudes, Relationships, Nutrition) (n = 73), and Ornish (n = 72) diet groups by using 3-d, unannounced 24-h recalls at baseline and after 8 wk of instruction. Nutrient intakes were compared between groups at 8 wk and within groups for 8-wk changes in risk of micronutrient inadequacy. RESULTS: At 8 wk, significant differences were observed between groups for all macronutrients and for many micronutrients (P < 0.0001). Energy intake decreased from baseline in all 4 groups but was similar between groups. At 8 wk, a significant proportion of individuals shifted to intakes associated with risk of inadequacy (P < 0.05) in the Atkins group for thiamine, folic acid, vitamin C, iron, and magnesium; in the LEARN group for vitamin E, thiamine, and magnesium; and in the Ornish group for vitamins E and B-12 and zinc. In contrast, for the Zone group, the risk of inadequacy significantly decreased for vitamins A, E, K, and C (P < 0.05), and no significant increases in risk of inadequacy were observed for other micronutrients. CONCLUSIONS: Weight-loss diets that focus on macronutrient composition should attend to the overall quality of the diet, including the adequacy of micronutrient intakes. Concerning calorie-restricted diets, there may be a micronutrient advantage to diets providing moderately low carbohydrate amounts and that contain nutrient-dense foods. PMID- 20573799 TI - Caffeine consumption and incident atrial fibrillation in women. AB - BACKGROUND: It is somewhat controversial whether caffeine consumption is associated with an increased risk of developing atrial fibrillation (AF). OBJECTIVE: We prospectively assessed the relation between caffeine intake and incident AF. DESIGN: A total of 33,638 initially healthy women who participated in the Women's Health Study and who were gt 45 y of age and free of cardiovascular disease and AF at baseline were prospectively followed for incident AF from 1993 to 2 March 2009. All women provided information on caffeine intake via food-frequency questionnaires at baseline and in 2004. RESULTS: During a median follow-up of 14.4 y (interquartile range: 13.8-14.8 y), 945 AF events occurred. Median caffeine intakes across increasing quintiles of caffeine intake were 22, 135, 285, 402, and 656 mg/d, respectively. Age-adjusted incidence rates of AF across increasing quintiles of caffeine intake were 2.15, 1.89, 2.01, 2.24, and 2.04 events, respectively, per 1000 person-years of follow-up. In Cox proportional hazards models updated in 2004 by using time-varying covariates, the corresponding multivariable-adjusted hazard ratios (95% CI) were 1.0, 0.88 (0.72, 1.06), 0.78 (0.64, 0.95), 0.96 (0.79, 1.16), and 0.89 (0.73, 1.09) (P for linear trend: 0.45). None of the individual components of caffeine intake (coffee, tea, cola, and chocolate) were significantly associated with incident AF. CONCLUSIONS: In this large cohort of initially healthy women, elevated caffeine consumption was not associated with an increased risk of incident AF. Therefore, our data suggest that elevated caffeine consumption does not contribute to the increasing burden of AF in the population. This trial was registered at clinicaltrials.gov as NCT00000479. PMID- 20573801 TI - Abrogation of NF-kappaB signaling in human neutrophils induces neutrophil survival through sustained p38-MAPK activation. AB - NF-kappaB, an important transcription factor in the regulation of cellular inflammation, is one of the prime targets for novel anti-inflammatory therapeutics. Nowadays, anti-inflammatory therapies rely mostly on steroids, which among other effects, inhibit NF-kappaB activity. However, steroids have only limited efficacy in the treatment on neutrophil-driven diseases, such as COPD. Human neutrophils play an important role in the pathogenesis of COPD, and clearance of these cells by apoptosis is an effective pathway for resolution of inflammation. In this study, we tested the hypothesis that modulation of the NF kappaB pathway in human neutrophils affects survival. Importantly, the pharmacological NF-kappaB inhibitor Bay 11-7082 inhibited NF-kappaB signaling in human neutrophils as expected. However, we found that complete inhibition of NF kappaB activity with 10 MUM Bay 11-7082 prolonged neutrophil survival significantly, which was not observed with inhibitors for other signaling pathways. Bay 11-7082-induced neutrophil survival was dependent on p38-MAPK kinase activity, as the p38 kinase activity inhibitor SB203580 abrogated this response completely. Bay 11-7082 induced rapid and sustained p38 activation that correlated with inhibited NF-kappaB signaling and prolonged neutrophil survival. The precise role of NF-kappaB in regulation of p38-MAPK activation remains to be established. Under these conditions of survival, the stability of Bcl-xL but not Mcl-1 was enhanced. Although inhibition of NF-kappaB leads to down-regulation of inflammatory genes in many cell types, our results illustrate that interference with basal NF-kappaB signaling in neutrophils as a drug target should be used with caution. PMID- 20573802 TI - NF-kappaB as a central regulator of macrophage function in tumors. AB - TAMs are usually abundant in the tumor microenvironment and are now known to play an essential role in tumor progression. For example, TAMs influence many aspects of tumorigenesis, such as the growth, survival, invasion, and metastasis of tumor cells, tumor angiogenesis, and the suppression of other tumor-infiltrating immune effector cells. The molecular pathways that regulate these tumor-promoting functions of TAMs are currently under intense investigation. Several recent studies about transgenic murine tumor models have shown that the transcription factor NF-kappaB is a key player in tumor progression with distinct roles in regulating the functions of macrophages and tumor cells in malignant tumors. Here, we outline the evidence for classical and noncanonical NF-kappaB signaling pathways driving the tumor-promoting repertoire of TAMs. PMID- 20573803 TI - Histidine-rich glycoprotein functions cooperatively with cell surface heparan sulfate on phagocytes to promote necrotic cell uptake. AB - Dying cells, such as apoptotic and necrotic cells, are cleared rapidly from the site of cell death to prevent the exposure of intracellular antigenic and immunostimulatory molecules that may cause tissue injury or facilitate the development of autoimmune diseases. For the immune system to recognize and remove dying cells efficiently, professional phagocytes use a variety of mechanisms that distinguish healthy cells from dying cells. HRG, a relatively abundant heparin/HS binding protein in human plasma, has been shown recently to tether IgG specifically to necrotic cells and aid the phagocytic uptake of necrotic cells via a FcgammaRI-dependent pathway. In this study, we provide direct evidence that HRG can function cooperatively with cell surface HS on the monocytic cell line THP-1 to promote necrotic cell removal. In addition, we found that the presence of heparin can markedly inhibit HRG-enhanced necrotic cell clearance by THP-1 cells, possibly by blocking the ability of HRG to interact with necrotic cells as well as THP-1 cells. Thus, these data suggest that HRG can aid the phagocytosis of necrotic cells via a HS-dependent pathway, and this process can be regulated by the presence of certain HRG ligands, such as heparin. PMID- 20573805 TI - Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long term renal function deterioration. AB - BACKGROUND: Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. METHODS: Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex matched controls (Group B) having liver transplantation for other indications. RESULTS: All patients received a liver graft from a deceased donor. Median follow up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). CONCLUSIONS: Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end stage renal disease and the need for renal transplantation. PMID- 20573804 TI - Oocyte activation, phospholipase C zeta and human infertility. AB - BACKGROUND: Mammalian oocytes are activated by intracellular calcium (Ca(2+)) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C zeta, PLCzeta, which is introduced into the oocyte following membrane fusion, as the responsible factor. This review summarizes the current understanding of human oocyte activation failure and describes recent discoveries linking certain cases of male infertility with defects in PLCzeta expression and activity. How these latest findings may influence future diagnosis and treatment options are also discussed. METHODS: Systematic literature searches were performed using PubMed, ISI-Web of Knowledge and The Cochrane Library. We also scrutinized material from the United Nations and World Health Organization databases (UNWHO) and the Human Fertilization and Embryology Authority (HFEA). RESULTS AND CONCLUSIONS: Although ICSI results in average fertilization rates of 70%, complete or virtually complete fertilization failure still occurs in 1-5% of ICSI cycles. While oocyte activation failure can, in some cases, be overcome by artificial oocyte activators such as calcium ionophores, a more physiological oocyte activation agent might release Ca(2+) within the oocyte in a more efficient and controlled manner. As PLCzeta is now widely considered to be the physiological agent responsible for activating mammalian oocytes, it represents both a novel diagnostic biomarker of oocyte activation capability and a possible mode of treatment for certain types of male infertility. PMID- 20573806 TI - Tranilast attenuates the up-regulation of thioredoxin-interacting protein and oxidative stress in an experimental model of diabetic nephropathy. AB - BACKGROUND: Diabetic nephropathy is the leading cause of kidney failure in the developed world. Tranilast has been reported to not only act as an anti inflammatory and anti-fibrotic compound, but it also exerts anti-oxidative stress effects in diabetic nephropathy. Thioredoxin-interacting protein (Txnip) is the endogenous inhibitor of the anti-oxidant thioredoxin and is highly up-regulated in diabetic nephropathy, leading to oxidative stress and fibrosis. In this study, we aimed to investigate whether tranilast exerts its anti-oxidant properties through the inhibition of Txnip. METHODS: Heterozygous Ren-2 rats were rendered diabetic with streptozotocin. Another group of rats were injected with citrate buffer alone and treated as non-diabetic controls. After 6 weeks of diabetes, diabetic rats were divided into two groups: one group gavaged with tranilast at 200 mg/kg/day and another group with vehicle. RESULTS: Diabetic rats had a significant increase in albuminuria, tubulointerstitial fibrosis, peritubular collagen IV accumulation, reactive oxygen species (ROS) and macrophage infiltration (all P < 0.05). These changes were associated with an increase in Txnip mRNA and protein expression in the tubules and glomeruli of diabetic kidney. Treatment with tranilast for 4 weeks significantly attenuated Txnip up regulation in diabetic rats and this was associated with a reduction in ROS, fibrosis and macrophage infiltration (all P < 0.05). CONCLUSIONS: This is the first study to demonstrate that tranilast not only has anti-inflammatory and anti fibrotic effects as previously reported but also attenuates the up-regulation of Txnip and oxidative stress in diabetic nephropathy. PMID- 20573807 TI - Behavioural abnormalities in children with nephrotic syndrome--an underappreciated complication of a standard treatment? AB - Behaviour and psychosocial adjustment are impaired in children with steroid sensitive idiopathic nephrotic syndrome (SSNS). Both illness-related variables and family climate play a role. Steroid treatment-both short- and long-term-is an important contributor among other determinants. The exact mechanisms by which steroids lead to behavioural alterations in humans is unclear. Optimizing the benefit/risk ratio of steroid treatment in children with SSNS is a constant goal. PMID- 20573808 TI - Alpha interferon and not gamma interferon inhibits salmonid alphavirus subtype 3 replication in vitro. AB - Salmonid alphavirus (SAV) is an emerging virus in salmonid aquaculture, with SAV 3 being the only subtype found in Norway. Until now, there has been little focus on the alpha interferon (IFN-alpha)-induced antiviral responses during virus infection in vivo or in vitro in fish. The possible involvement of IFN-gamma in the response to SAV-3 is also not known. In this study, the two IFNs were cloned and expressed as recombinant proteins (recombinant IFN-alpha [rIFN-alpha] and rIFN-gamma) and used for in vitro studies. SAV-3 infection in a permissive salmon cell line (TO cells) results in IFN-alpha and IFN-stimulated gene (ISG) mRNA upregulation. Preinfection treatment (4 to 24 h prior to infection) with salmon rIFN-alpha induces an antiviral state that inhibits the replication of SAV-3 and protects the cells against virus-induced cytopathic effects (CPE). The antiviral state coincides with a strong expression of Mx and ISG15 mRNA and Mx protein expression. When rIFN-alpha is administered at the time of infection and up to 24 h postinfection, virus replication is not inhibited, and cells are not protected against virus-induced CPE. By 40 h postinfection, the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) is phosphorylated concomitant with the expression of the E2 protein as assessed by Western blotting. Postinfection treatment with rIFN-alpha results in a moderate reduction in E2 expression levels in accordance with a moderate downregulation of cellular protein synthesis, an approximately 65% reduction by 60 h postinfection. rIFN-gamma has only a minor inhibitory effect on SAV-3 replication in vitro. SAV-3 is sensitive to the preinfection antiviral state induced by rIFN-alpha, while postinfection antiviral responses or postinfection treatment with rIFN-alpha is not able to limit viral replication. PMID- 20573809 TI - Replacement of the replication factors of porcine circovirus (PCV) type 2 with those of PCV type 1 greatly enhances viral replication in vitro. AB - Porcine circovirus type 1 (PCV1), originally isolated as a contaminant of PK-15 cells, is nonpathogenic, whereas porcine circovirus type 2 (PCV2) causes an economically important disease in pigs. To determine the factors affecting virus replication, we constructed chimeric viruses by swapping open reading frame 1 (ORF1) (rep) or the origin of replication (Ori) between PCV1 and PCV2 and compared the replication efficiencies of the chimeric viruses in PK-15 cells. The results showed that the replication factors of PCV1 and PCV2 are fully exchangeable and, most importantly, that both the Ori and rep of PCV1 enhance the virus replication efficiencies of the chimeric viruses with the PCV2 backbone. PMID- 20573810 TI - Identification of cross-reactive norovirus CD4+ T cell epitopes. AB - Immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. Although antibody responses following norovirus infection have been partially characterized, T cell responses in humans remain largely undefined. In contrast, T cells have been shown to be essential for viral clearance of mouse norovirus (MNV) infection. In this paper, we demonstrate that CD4(+) T cells secrete gamma interferon (IFN-gamma) in response to stimulation with MNV virus-like particles (VLPs) after MNV infection, supporting earlier reports for norovirus-infected mice and humans. Utilizing this model, we immunized mice with alphavirus vectors (Venezuelan equine encephalitis [VEE] virus replicon particles [VRPs]) expressing Norwalk virus (NV) or Farmington Hills virus (FH) virus-like particles to evaluate T cell epitopes shared between human norovirus strains. Stimulation of splenocytes from norovirus VRP-immunized mice with overlapping peptides from complete libraries of the NV or FH capsid proteins revealed specific amino acid sequences containing T cell epitopes that were conserved within genoclusters and genogroups. Immunization with heterologous norovirus VRPs resulted in specific cross-reactive IFN-gamma secretion profiles following stimulation with NV and FH peptides in the mouse. Identification of unique strain-specific and cross-reactive epitopes may provide insight into homologous and heterologous T cell-mediated norovirus immunity and provide a platform for the study of norovirus-induced cellular immunity in humans. PMID- 20573811 TI - The triplet repeats of the Sin Nombre hantavirus 5' untranslated region are sufficient in cis for nucleocapsid-mediated translation initiation. AB - Hantavirus nucleocapsid protein (N) can replace the cellular cap-binding complex, eukaryotic initiation factor 4F (eIF4F), to mediate translation initiation. Although N can augment translation initiation of nonviral mRNA, initiation of viral mRNA by N is superior. All members of the Bunyaviridae family, including the species of the hantavirus genus, express either three or four primary mRNAs from their tripartite negative-sense genomes. The 5' ends of the mRNAs contain nonviral heterologous oligonucleotides that originate from endonucleolytic cleavage of cellular mRNA during the process of cap snatching. In the hantaviruses these caps terminate with a 3' G residue followed by nucleotides arising from the viral template. Further, the 5' untranslated region (UTR) of viral mRNA uniformly contains, near the 5' end, either two or three copies of the triplet repeat sequence, UAGUAG or UAGUAGUAG. Through analysis of a panel of mutants with mutations in the viral UTR, we found that the sequence GUAGUAG is sufficient for preferential N-mediated translation initiation and for high affinity binding of N to the UTR. This heptanucleotide sequence is present in viral mRNA containing either two or three copies of the triplet repeat. PMID- 20573812 TI - In vitro assembly of the T=13 procapsid of bacteriophage T5 with its scaffolding domain. AB - The Siphoviridae coliphage T5 differs from other members of this family by the size of its genome (121 kbp) and by its large icosahedral capsid (90 nm), which is organized with T=13 geometry. T5 does not encode a separate scaffolding protein, but its head protein, pb8, contains a 159-residue aminoterminal scaffolding domain (Delta domain) that is the mature capsid. We have deciphered the early events of T5 shell assembly starting from purified pb8 with its Delta domain (pb8p). The self assembly of pb8p is regulated by salt conditions and leads to structures with distinct morphologies. Expanded tubes are formed in the presence of NaCl, whereas Ca(2+) promotes the association of pb8p into contracted tubes and procapsids. Procapsids display an angular organization and 20-nm-long internal radial structures identified as the Delta domain. The T5 head maturation protease pb11 specifically cleaves the Delta domain of contracted and expanded tubes. Ca(2+) is not required for proteolytic activity but for the organization of the Delta domain. Taken together, these data indicate that pb8p carries all of the information in its primary sequence to assemble in vitro without the requirement of the portal and accessory proteins. Furthermore, Ca(2+) plays a key role in introducing the conformational diversity that permits the formation of a stable procapsid. Phage T5 is the first example of a viral capsid consisting of quasi-equivalent hexamers and pentamers whose assembly can be carried out in vitro, starting from the major head protein with its scaffolding domain, and whose endpoint is an icosahedral T=13 particle. PMID- 20573813 TI - Distinct molecular pathways to X4 tropism for a V3-truncated human immunodeficiency virus type 1 lead to differential coreceptor interactions and sensitivity to a CXCR4 antagonist. AB - During the course of infection, transmitted HIV-1 isolates that initially use CCR5 can acquire the ability to use CXCR4, which is associated with an accelerated progression to AIDS. Although this coreceptor switch is often associated with mutations in the stem of the viral envelope (Env) V3 loop, domains outside V3 can also play a role, and the underlying mechanisms and structural basis for how X4 tropism is acquired remain unknown. In this study we used a V3 truncated R5-tropic Env as a starting point to derive two X4-tropic Envs, termed DeltaV3-X4A.c5 and DeltaV3-X4B.c7, which took distinct molecular pathways for this change. The DeltaV3-X4A.c5 Env clone acquired a 7-amino-acid insertion in V3 that included three positively charged residues, reestablishing an interaction with the CXCR4 extracellular loops (ECLs) and rendering it highly susceptible to the CXCR4 antagonist AMD3100. In contrast, the DeltaV3-X4B.c7 Env maintained the V3 truncation but acquired mutations outside V3 that were critical for X4 tropism. In contrast to DeltaV3-X4A.c5, DeltaV3-X4B.c7 showed increased dependence on the CXCR4 N terminus (NT) and was completely resistant to AMD3100. These results indicate that HIV-1 X4 coreceptor switching can involve (i) V3 loop mutations that establish interactions with the CXCR4 ECLs, and/or (ii) mutations outside V3 that enhance interactions with the CXCR4 NT. The cooperative contributions of CXCR4 NT and ECL interactions with gp120 in acquiring X4 tropism likely impart flexibility on pathways for viral evolution and suggest novel approaches to isolate these interactions for drug discovery. PMID- 20573814 TI - Elevated cyclic AMP levels in T lymphocytes transformed by human T-cell lymphotropic virus type 1. AB - Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of adult T-cell leukemia/lymphoma (ATLL), transforms CD4(+) T cells to permanent growth through its transactivator Tax. HTLV-1-transformed cells share phenotypic properties with memory and regulatory T cells (T-reg). Murine T-reg-mediated suppression employs elevated cyclic AMP (cAMP) levels as a key regulator. This led us to determine cAMP levels in HTLV-1-transformed cells. We found elevated cAMP concentrations as a consistent feature of all HTLV-1-transformed cell lines, including in vitro HTLV-1-transformed, Tax-transformed, and patient-derived cells. In transformed cells with conditional Tax expression, high cAMP levels coincided with the presence of Tax but were lost without it. However, transient ectopic expression of Tax alone was not sufficient to induce cAMP. We found specific downregulation of the cAMP-degrading phosphodiesterase 3B (PDE3B) in HTLV-1-transformed cells, which was independent of Tax in transient expression experiments. This is in line with the notion that PDE3B transcripts and cAMP levels are inversely correlated. Overexpression of PDE3B led to a decrease of cAMP in HTLV-1-transformed cells. Decreased expression of PDE3B was associated with inhibitory histone modifications at the PDE3B promoter and the PDE3B locus. In summary, Tax transformation and its continuous expression contribute to elevated cAMP levels, which may be regulated through PDE3B suppression. This shows that HTLV-1 transformed cells assume biological features of long-lived T-cell populations that potentially contribute to viral persistence. PMID- 20573815 TI - Identification of rep-associated factors in herpes simplex virus type 1-induced adeno-associated virus type 2 replication compartments. AB - Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase delta was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, 3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus. PMID- 20573817 TI - Modeling adenovirus latency in human lymphocyte cell lines. AB - Species C adenovirus establishes a latent infection in lymphocytes of the tonsils and adenoids. To understand how this lytic virus is maintained in these cells, four human lymphocytic cell lines that support the entire virus life cycle were examined. The T-cell line Jurkat ceased proliferation and died shortly after virus infection. BJAB, Ramos (B cells), and KE37 (T cells) continued to divide at nearly normal rates while replicating the virus genome. Viral genome numbers peaked and then declined in BJAB cells below one genome per cell at 130 to 150 days postinfection. Ramos and KE37 cells maintained the virus genome at over 100 copies per cell over a comparable period of time. BJAB cells maintained the viral DNA as a monomeric episome. All three persistently infected cells lost expression of the cell surface coxsackie and adenovirus receptor (CAR) within 24 h postinfection, and CAR expression remained low for at least 340 days postinfection. CAR loss proceeded via a two-stage process. First, an initial loss of cell surface staining for CAR required virus late gene expression and a CAR binding fiber protein even while CAR protein and mRNA levels remained high. Second, CAR mRNA disappeared at around 30 days postinfection and remained low even after virus DNA was lost from the cells. At late times postinfection (day 180), BJAB cells could not be reinfected with adenovirus, even when CAR was reintroduced to the cells via retroviral transduction, suggesting that the expression of multiple genes had been stably altered in these cells following infection. PMID- 20573816 TI - Activation of the interferon response by human cytomegalovirus occurs via cytoplasmic double-stranded DNA but not glycoprotein B. AB - In vitro infection of cells with the betaherpesvirus human cytomegalovirus (HCMV) stimulates an innate immune response characterized by phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent expression of IRF3-dependent genes. While previous work suggests that HCMV envelope glycoprotein B is responsible for initiating this reaction, the signaling pathways stimulated by virus infection that lead to IRF3 phosphorylation have largely been uncharacterized. Recently, we identified Z DNA binding protein 1 (ZBP1), a sensor of cytoplasmic DNA, as an essential protein for this response. We now describe a human fibroblast cell line exhibiting a recessive defect that results in the absence of activation of IRF3 following treatment with HCMV but not Sendai virus or double-stranded RNA. In addition, we show that while exposure of these cells to soluble HCMV glycoprotein B is capable of triggering IRF3-dependent gene transcription, transfection of the cells with double-stranded DNA is not. Furthermore, we show that overexpression of ZBP1 in these cells reestablishes their ability to secrete interferon in response to HCMV and that multiple ZBP1 transcriptional variants exist in both wild-type and mutant cells. These results have two major implications for the understanding of innate immune stimulation by HCMV. First, they demonstrate that HCMV glycoprotein B is not the essential molecular pattern that induces an IRF3-dependent innate immune response. Second, IRF3-terminal signaling triggered by HCMV particles closely resembles that which is activated by cytoplasmic double-stranded DNA. PMID- 20573818 TI - Baculovirus GP64 disulfide bonds: the intermolecular disulfide bond of Autographa californica multicapsid nucleopolyhedrovirus GP64 is not essential for membrane fusion and virion budding. AB - The GP64 envelope glycoprotein of the Autographa californica nucleopolyhedrovirus (AcMNPV) is a class III viral membrane fusion protein that is triggered by low pH during entry. Unlike most other viral fusion protein trimers, the monomers of GP64 are covalently linked to each other within the trimer by a single intermolecular disulfide bond (Cys24 Cys372). Single or paired alanine substitutions for Cys24 and Cys372 resulted in lower-efficiency transport of GP64 to the cell surface. Surprisingly, these mutated GP64s induced syncytium formation, and normalized fusion activities were approximately 30% of that from wild-type (WT) GP64. Heat treatment (37 degrees C) did not further reduce fusion activity of GP64 constructs with a disrupted intermolecular disulfide bond, suggesting that the GP64 trimers were relatively thermostable in the absence of the intermolecular disulfide bond. In addition, analysis of binding by a conformation-specific monoclonal antibody (MAb) suggested that the low-pH-induced refolding of those GP64 constructs was generally similar to that of WT GP64. In addition to its critical role in membrane fusion, GP64 is also necessary for efficient budding. When GP64 constructs containing a disrupted intermolecular disulfide bond (Cys24 Cys372) were displayed at the cell surface at levels comparable to those of WT GP64, virion budding efficiency ranged from approximately 39 to 88%, indicating that the intermolecular disulfide bond is not required for virion budding. However, GP64 proteins with a disrupted intermolecular disulfide could not rescue a GP64-null bacmid. We also examined the 6 conserved intramolecular disulfide bonds using single and paired alanine substitution mutations. None of the GP64 constructs with disrupted intramolecular disulfide bonds were capable of mediating pH-triggered membrane fusion, indicating that the intramolecular disulfide bonds are all necessary for membrane fusion. Thus, while the intramolecular disulfide bonds of GP64 appear to serve critical roles in membrane fusion, the unusual intermolecular disulfide bond was not critical for membrane fusion or virion budding yet appears to play an unknown role in viral infectivity. PMID- 20573819 TI - Poly(A)-binding protein 1 partially relocalizes to the nucleus during herpes simplex virus type 1 infection in an ICP27-independent manner and does not inhibit virus replication. AB - Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shutoff whereby mRNAs are degraded and cellular protein synthesis is diminished. However, virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A) binding protein 1 (PABP1), a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalization occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. An examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of JNK and p38 mitogen activated protein (MAP) kinases. Importantly, PABP relocalization in infection was found to be independent of the viral protein ICP27. The depletion of PABP1 by small interfering RNA (siRNA) knockdown had no significant effect on viral replication or the expression of selected virus late proteins, suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection. PMID- 20573820 TI - Mutagenesis of adeno-associated virus type 2 capsid protein VP1 uncovers new roles for basic amino acids in trafficking and cell-specific transduction. AB - The N termini of the capsid proteins VP1 and VP2 of adeno-associated virus (AAV) play important roles in subcellular steps of infection and contain motifs that are highly homologous to a phospholipase A(2) (PLA(2)) domain and nuclear localization signals (NLSs). To more clearly understand how virion components influence infection, we have generated mutations in these regions and examined their effects on subcellular trafficking, capsid stability, transduction, and sensitivity to pharmacological enhancement. All mutants tested assembled into capsids; retained the correct ratio of VP1, VP2, and VP3; packaged DNA similarly to recombinant AAV2 (rAAV2); and displayed similar stability profiles when heat denatured. Confocal microscopy demonstrated that these mutants trafficked through a perinuclear region in the vicinity of the Golgi apparatus, with a subset of mutants displaying more-diffuse localization consistent with an NLS-deficient phenotype. When tested for viral transduction, two mutant classes emerged. Class I (BR1(-), BR2(-), and BR2+K) displayed partial transduction, whereas class II (VP3 only, (75)HD/AN, BR3(-), and BR3+K) were severely defective. Surprisingly, one class II mutant (BR3+K) trafficked identically to rAAV2 and accumulated in the nucleolus, a step recently described by our laboratory that occurs with wild type infection. The BR3+K mutant, containing an alanine-to-lysine substitution in the third basic region of VP1, was 10- to 100-fold-less infectious than rAAV2 in transformed cell lines (such as HEK-293, HeLa, and CV1-T cells), but in contrast, it was indistinguishable from rAAV2 in several nontransformed cell lines, as well as in tissues (liver, brain, and muscle) in vivo. Complementation studies with pharmacological adjuvants or adenovirus coinfection suggested that additional positive charges in NLS regions restrict mobilization in the nucleus and limit transduction in a transformed-cell-specific fashion. Remarkably, besides displaying cell-type-specific transduction, this is the first description of a capsid mutant indicating that nuclear entry is not sufficient for AAV-mediated transduction and suggests that additional steps (i.e., subnuclear mobilization or uncoating) limit successful AAV infection. PMID- 20573821 TI - Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion. AB - Following herpes simplex virus type 1 (HSV-1) ocular infection of C57BL/6 mice, activated CD8(+) T cells specific for an immunodominant epitope on HSV-1 glycoprotein B (gB-CD8 cells) establish a stable memory population in HSV-1 latently infected trigeminal ganglia (TG), whereas non-HSV-specific CD8(+) T cells are lost over time. The retention and activation of gB-CD8 cells appear to be influenced by persistent viral antigenic exposure within the latently infected TG. We hypothesized that the low-level expression of gB from its native promoter before viral DNA synthesis is critical for the retention and activation of gB-CD8 cells in the TG during HSV-1 latency and for their ability to block HSV-1 reactivation from latency. To test this, we created a recombinant HSV-1 in which gB is expressed only after viral DNA synthesis from the true late gC promoter (gCp-gB). Despite minor growth differences compared to its rescuant in infected corneas, gCp-gB was significantly growth impaired in the TG and produced a reduced latent genome load. The gCp-gB- and rescuant-infected mice mounted similar gB-CD8 effector responses, but the size and activation phenotypes of the memory gB-CD8 cells were diminished in gCp-gB latently infected TG, suggesting that the stimulation of gB-CD8 cells requires gB expression before viral DNA synthesis. Surprisingly, late gB expression did not compromise the capacity of gB CD8 cells to inhibit HSV-1 reactivation from latency in ex vivo TG cultures, suggesting that gB-CD8 cells can block HSV-1 reactivation at a very late stage in the viral life cycle. These data have implications for designing better immunogens for vaccines to prevent HSV-1 reactivation. PMID- 20573822 TI - CD25+ natural regulatory T cells are critical in limiting innate and adaptive immunity and resolving disease following respiratory syncytial virus infection. AB - Regulatory CD4(+) T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4(+) Foxp3(+) CD25(+) natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25(+) natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL 6) and gamma interferon (IFN-gamma). CD25(+) natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-gamma and tumor necrosis factor alpha (TNF-alpha) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections. PMID- 20573823 TI - Temporal and spatial resolution of type I and III interferon responses in vivo. AB - Although the action of interferons (IFNs) has been extensively studied in vitro, limited information is available on the spatial and temporal activation pattern of IFN-induced genes in vivo. We created BAC transgenic mice expressing firefly luciferase under transcriptional control of the Mx2 gene promoter. Expression of the reporter with regard to onset and kinetics of induction parallels that of Mx2 and is thus a hallmark for the host response. Substantial constitutive expression of the reporter gene was observed in the liver and most other tissues of transgenic mice, whereas this expression was strongly reduced in animals lacking functional type I IFN receptors. As expected, the reporter gene was induced not only in response to type I (alpha and beta) and type III (lambda) IFNs but also in response to a variety of IFN inducers such as double-stranded RNA, lipopolysaccharide (LPS), and viruses. In vivo IFN subtypes show clear differences with respect to their kinetics of action and to their spatial activation pattern: while the type I IFN response was strong in liver, spleen, and kidney, type III IFN reactivity was most prominent in organs with mucosal surfaces. Infection of reporter mice with virus strains that differ in their pathogenicity shows that the IFN response is significantly altered in the strength of IFN action at sites which are not primarily infected as well as by the onset and duration of gene induction. PMID- 20573824 TI - Visualizing the replication cycle of bunyamwera orthobunyavirus expressing fluorescent protein-tagged Gc glycoprotein. AB - The virion glycoproteins Gn and Gc of Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family and also of the Orthobunyavirus genus, are encoded by the medium (M) RNA genome segment and are involved in both viral attachment and entry. After their synthesis Gn and Gc form a heterodimer in the endoplasmic reticulum (ER) and transit to the Golgi compartment for virus assembly. The N terminal half of the Gc ectodomain was previously shown to be dispensable for virus replication in cell culture (X. Shi, J. Goli, G. Clark, K. Brauburger, and R. M. Elliott, J. Gen. Virol. 90:2483-2492, 2009.). In this study, the coding sequence for a fluorescent protein, either enhanced green fluorescent protein (eGFP) or mCherry fluorescent protein, was fused to the N terminus of truncated Gc, and two recombinant BUNVs (rBUNGc-eGFP and rBUNGc-mCherry) were rescued by reverse genetics. The recombinant viruses showed bright autofluorescence under UV light and were competent for replication in various mammalian cell lines. rBUNGc mCherry was completely stable over 10 passages, whereas internal, in-frame deletions occurred in the chimeric Gc-eGFP protein of rBUNGc-eGFP, resulting in loss of fluorescence between passages 5 and 7. Autofluorescence of the recombinant viruses allowed visualization of different stages of the infection cycle, including virus attachment to the cell surface, budding of virus particles in Golgi membranes, and virus-induced morphological changes to the Golgi compartment at later stages of infection. The fluorescent protein-tagged viruses will be valuable reagents for live-cell imaging studies to investigate virus entry, budding, and morphogenesis in real time. PMID- 20573825 TI - Characterization of the host immune response in human Ganglia after herpes zoster. AB - Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia, from where it reactivates to cause herpes zoster (shingles), which is often followed by postherpetic neuralgia (PHN), causing severe neuropathic pain that can last for years after the rash. Despite the major impact of herpes zoster and PHN on quality of life, the nature and kinetics of the virus immune cell interactions that result in ganglion damage have not been defined. We obtained rare material consisting of seven sensory ganglia from three donors who had suffered from herpes zoster between 1 and 4.5 months before death but who had not died from herpes zoster. We performed immunostaining to investigate the site of VZV infection and to phenotype immune cells in these ganglia. VZV antigen was localized almost exclusively to neurons, and in at least one case it persisted long after resolution of the rash. The large immune infiltrate consisted of noncytolytic CD8(+) T cells, with lesser numbers of CD4(+) T cells, B cells, NK cells, and macrophages and no dendritic cells. VZV antigen-positive neurons did not express detectable major histocompatibility complex (MHC) class I, nor did CD8(+) T cells surround infected neurons, suggesting that mechanisms of immune control may not be dependent on direct contact. This is the first report defining the nature of the immune response in ganglia following herpes zoster and provides evidence for persistence of non-latency-associated viral antigen and inflammation beyond rash resolution. PMID- 20573826 TI - Nucleocytoplasmic shuttling of human cytomegalovirus UL84 is essential for virus growth. AB - Human cytomegalovirus (HCMV) UL84 is a multifunctional protein that is the proposed initiator for lytic viral DNA synthesis. Recently it was shown that UL84 displays nucleocytoplasmic shuttling. The role of shuttling in lytic DNA replication and virus growth is unknown. We now show that expression of the nonshuttling UL84 mutant failed to complement oriLyt-dependent DNA replication in the transient assay under conditions where core replication and ancillary proteins were expressed under the control of their native promoters. However, constitutive expression of the core replication proteins, along with the nonshuttling UL84 mutant, resulted in efficient oriLyt amplification, suggesting that shuttling may contribute to the activity of one of the auxiliary replication proteins. A recombinant HCMV bacterial artificial chromosome plasmid (BACmid) expressing the nonshuttling UL84 mutant (NS84 BAC) was defective for production of infectious virus. Quantitative PCR showed that NS84 BAC had decreased accumulation of viral DNA in both cellular and supernatant samples. Analysis of the accumulation of select viral mRNAs showed no difference in total cellular mRNA accumulation for IE2, IRS1, TRS1, UL102, UL105, and UL75 in cells transfected with the NS84 BAC. However, examination of cytoplasmic RNA and subcellular localization of IRS1 revealed a decrease in IRS1 mRNA accumulation and displaced protein localization, strongly suggesting that UL84 facilitated the localization of IRS1 mRNA to the cytoplasm. RNA pulldown assays showed that UL84 interacted with IRS1 mRNA. These results indicate that nucleocytoplasmic shuttling is essential for virus growth and strongly suggest that UL84 is responsible for localization of at least one virus-encoded transcript, IRS1 mRNA. PMID- 20573827 TI - The cellular RNA helicase DDX1 interacts with coronavirus nonstructural protein 14 and enhances viral replication. AB - The involvement of host proteins in the replication and transcription of viral RNA is a poorly understood area for many RNA viruses. For coronaviruses, it was long speculated that replication of the giant RNA genome and transcription of multiple subgenomic mRNA species by a unique discontinuous transcription mechanism may require host cofactors. To search for such cellular proteins, yeast two-hybrid screening was carried out by using the nonstructural protein 14 (nsp14) from the coronavirus infectious bronchitis virus (IBV) as a bait protein, leading to the identification of DDX1, a cellular RNA helicase in the DExD/H helicase family, as a potential interacting partner. This interaction was subsequently confirmed by coimmunoprecipitation assays with cells coexpressing the two proteins and with IBV-infected cells. Furthermore, the endogenous DDX1 protein was found to be relocated from the nucleus to the cytoplasm in IBV infected cells. In addition to its interaction with IBV nsp14, DDX1 could also interact with the nsp14 protein from severe acute respiratory syndrome coronavirus (SARS-CoV), suggesting that interaction with DDX1 may be a general feature of coronavirus nsp14. The interacting domains were mapped to the C terminal region of DDX1 containing motifs V and VI and to the N-terminal portion of nsp14. Manipulation of DDX1 expression, either by small interfering RNA induced knockdown or by overexpression of a mutant DDX1 protein, confirmed that this interaction may enhance IBV replication. This study reveals that DDX1 contributes to efficient coronavirus replication in cell culture. PMID- 20573828 TI - Association of the influenza virus RNA polymerase subunit PB2 with the host chaperonin CCT. AB - The RNA polymerase of influenza A virus is a host range determinant and virulence factor. In particular, the PB2 subunit of the RNA polymerase has been implicated as a crucial factor that affects cell tropism as well as virulence in animal models. These findings suggest that host factors associating with the PB2 protein may play an important role during viral replication. In order to identify host factors that associate with the PB2 protein, we purified recombinant PB2 from transiently transfected mammalian cells and identified copurifying host proteins by mass spectrometry. We found that the PB2 protein associates with the cytosolic chaperonin containing TCP-1 (CCT), stress-induced phosphoprotein 1 (STIP1), FK506 binding protein 5 (FKBP5), alpha- and beta-tubulin, Hsp60, and mitochondrial protein p32. Some of these binding partners associate with each other, suggesting that PB2 might interact with these proteins in multimeric complexes. More detailed analysis of the interaction of the PB2 protein with CCT revealed that PB2 associates with CCT as a monomer and that the CCT binding site is located in a central region of the PB2 protein. PB2 proteins from various influenza virus subtypes and origins can associate with CCT. Silencing of CCT resulted in reduced viral replication and reduced PB2 protein and viral RNA accumulation in a ribonucleoprotein reconstitution assay, suggesting an important function for CCT during the influenza virus life cycle. We propose that CCT might be acting as a chaperone for PB2 to aid its folding and possibly its incorporation into the trimeric RNA polymerase complex. PMID- 20573829 TI - PDZD8 is a novel Gag-interacting factor that promotes retroviral infection. AB - In a yeast two-hybrid screen for cellular factors that could interact with human immunodeficiency virus type 1 (HIV-1) Gag protein, we identified PDZD8 and confirmed the interaction by coimmunoprecipitation (co-IP). PDZD8 overexpression promoted the initiation of reverse transcription and increased infection by pseudotyped retroviruses independent of the route of viral entry, while transient knockdown of endogenous levels decreased HIV-1 infection. A mutant of PDZD8 lacking a predicted coiled-coil domain in its Gag-interacting region failed to bind Gag and promote HIV-1 infection, identifying the domain of PDZD8 required for mediating these effects. As such, we identify PDZD8 as a novel positive mediator of retroviral infection. PMID- 20573830 TI - The Ig-like v-type domain of paired Ig-like type 2 receptor alpha is critical for herpes simplex virus type 1-mediated membrane fusion. AB - Paired immunoglobulin (Ig)-like type 2 receptor alpha (PILRalpha) and PILRbeta are paired receptors that are highly homologous to each other. When engaged by ligand, PILRalpha is inhibitory whereas PILRbeta is activating. PILRalpha is a newly identified herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) receptor and is associated with membrane fusion and entry activity of HSV-1. PILRalpha is a 303-amino-acid protein with an Ig-like V (variable)-type domain from amino acid 31 to 150, whereas PILRbeta is a 217-amino-acid protein with an Ig-like V-type domain from amino acid 21 to 143. We report that PILRbeta is not a receptor for HSV-1 and HSV-2. Domain swaps between PILRalpha and PILRbeta reveal that the Ig like V-type domain of PILRalpha, but not PILRbeta, plays a critical role in cell membrane fusion activity and the binding of PILRalpha to gB. Individual replacement of 13 amino acids in PILRalpha showed that most of these mutations had no effect on cell fusion activity. However, mutation of the tryptophan residue at amino acid 139 significantly impaired cell fusion activity for HSV-1 and eliminated binding to gB. PMID- 20573831 TI - Myc is required for the maintenance of Kaposi's sarcoma-associated herpesvirus latency. AB - Myc is deregulated by Kaposi's sarcoma-associated herpesvirus (KSHV) latent proteins, but its role in KSHV latency is not clear. We found that Myc knockdown with RNA interference (RNAi) induced KSHV reactivation and increased the protein and mRNA levels of RTA, a key viral regulator of KSHV reactivation. Myc knockdown increased, whereas Myc overexpression inhibited, RTA promoter activity. KSHV reactivation and the activation of the RTA promoter induced by Myc depletion were inhibited by c-Jun N-terminal kinase (JNK) and p38 inhibitors but not by a MEK1 inhibitor. Myc knockdown inhibited primary effusion lymphoma (PEL) cell proliferation through inducing apoptosis and G(1) cell cycle arrest. Thus, Myc may be a key cellular node coupling cellular transformation and KSHV latency. PMID- 20573832 TI - Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles. AB - The cytoplasmic tail of the influenza A virus M2 protein is required for the production of infectious virions. In this study, critical residues in the M2 cytoplasmic tail were identified by single-alanine scanning mutagenesis. The tyrosine residue at position 76, which is conserved in >99% of influenza virus strains sequenced to date, was identified as being critical for the formation of infectious virus particles using both reverse genetics and a protein trans complementation assay. Recombinant viruses encoding M2 with the Y76A mutation demonstrated replication defects in MDCK cells as well as in primary differentiated airway epithelial cell cultures, defects in the formation of filamentous virus particles, and reduced packaging of nucleoprotein into virus particles. These defects could all be overcome by a mutation of serine to tyrosine at position 71 of the M2 cytoplasmic tail, which emerged after blind passage of viruses containing the Y76A mutation. These data confirm and extend our understanding of the significance of the M2 protein for infectious virus particle assembly. PMID- 20573833 TI - The herpes simplex virus type 1 UL20 protein and the amino terminus of glycoprotein K (gK) physically interact with gB. AB - Herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) and the UL20 protein (UL20p) are strictly required for virus-induced cell fusion, and mutations within either the gK or UL20 gene cause extensive cell fusion (syncytium formation). We have shown that gK forms a functional protein complex with UL20p, which is required for all gK and UL20p-associated functions in the HSV-1 life cycle. Recently, we showed that the amino-terminal 82 amino acids (aa) of gK (gKa) were required for the expression of the syncytial phenotype of the mutant virus gBDelta28 lacking the carboxyl-terminal 28 amino acids of gB (V. N. Chouljenko, A. V. Iyer, S. Chowdhury, D. V. Chouljenko, and K. G. Kousoulas, J. Virol. 83:12301-12313, 2009). This work suggested that the amino terminus of gK may directly or indirectly interact with gB and/or other viral glycoproteins. Two-way coimmunoprecipitation experiments revealed that UL20p interacted with gB in infected cells. Furthermore, the gKa peptide was coimmunoprecipitated with gB but not gD. Three recombinant baculoviruses were constructed, expressing the amino terminal 82 aa of gKa together with either the extracellular portion of gB (30 to 748 aa), gD (1 to 340 aa), or gH (1 to 792 aa), respectively. Coimmunoprecipitation experiments revealed that gKa physically interacted with the extracellular portions of gB and gH but not gD. Three additional recombinant baculoviruses expressing gKa and truncated gBs encompassing aa 30 to 154, 30 to 364, and 30 to 500 were constructed. Coimmunoprecipitation experiments showed that gKa physically interacted with all three truncated gBs. Computer-assisted prediction of possible gKa binding sites on gB suggested that gKa may interact predominantly with gB domain I (E. E. Heldwein, H. Lou, F. C. Bender, G. H. Cohen, R. J. Eisenberg, and S. C. Harrison, Science 313:217-220, 2006). These results imply that the gK/UL20p protein complex modulates the fusogenic properties of gB and gH via direct physical interactions. PMID- 20573834 TI - Distinct intracellular trafficking of hepatitis C virus in myeloid and plasmacytoid dendritic cells. AB - Dendritic cells (DCs) are of pivotal importance for the initiation of immune responses to control and eliminate viral infections. The molecular mechanisms of hepatitis C virus (HCV) antigen uptake and processing by blood DCs are poorly defined. Here we show that human blood DC subsets acquire HCV independent of the classical HCV entry factors. Following HCV uptake, human plasmacytoid and myeloid DC subsets deliver HCV antigen into distinct endocytotic compartments, which are dedicated to presentation to CD4(+) or CD8(+) T cells. Our findings support a model of HCV antigen processing and presentation in which DC subsets fulfill distinct functions. PMID- 20573837 TI - Long-term mortality in patients diagnosed with pneumococcal meningitis: a Danish nationwide cohort study. AB - The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through 2006 and alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. The absolute and relative risks of all-cause and cause-specific death were analyzed by using Kaplan-Meier survival curves, Poisson regression analysis, Cox regression analysis, and cumulative incidence functions. The authors identified 2,131 pneumococcal meningitis patients and an age- and gender-matched, population based cohort of 8,524 individuals. Compared with the background population, the pneumococcal meningitis patients had an increased long-term mortality varying from an 8-fold increased mortality in the age category 0-<20 years to a 1.5-fold increased mortality in those aged 60-<80 years. The increased risk of death stemmed from neoplasms, liver diseases, and nervous system diseases. The excess mortality due to neoplasms stemmed mainly from a 5-fold increased risk of death due to hematologic neoplasms. To improve survival in patients surviving the acute phase of pneumococcal meningitis, physicians should meticulously screen this patient population for neurologic sequelae and comorbidity predisposing to the disease. PMID- 20573836 TI - V(alpha)14iNKT cells promote liver pathology during adenovirus infection by inducing CCL5 production: implications for gene therapy. AB - Replication-defective recombinant adenoviruses are the most widely studied replication-defective vectors for the potential treatment of inherited human diseases. However, broad clinical application of replication-defective adenoviruses in gene therapy is being hindered by the induction of vigorous innate and adaptive immune responses against the vector that cause deleterious effects in the liver. V(alpha)14 invariant natural killer T cells (V(alpha)14iNKT cells) are thymus-derived innate T cells at the interface between the two arms of the immune response and provide full engagement of host defense. The pathophysiological role of intrahepatic V(alpha)14iNKT cells during replication defective adenovirus infection is not known and is the main focus of our study. Our data showed that intrahepatic V(alpha)14iNKT cells were activated in response to adenovirus infection to induce significant levels of hepatic chemokine (C-C motif) ligand 5 (CCL5) and subsequent liver toxicity. Moreover, intrahepatic CCL5 production was selectively reduced by V(alpha)14iNKT cell deficiency. In vivo studies utilizing CCL5-deficient mice or V(alpha)14iNKT cell-deficient mice demonstrated that CCL5 deficiency or V(alpha)14iNKT cell deficiency was associated with reduced liver pathology. Similar results were seen after blocking the biological effects of the CCL5 receptors. In conclusion, we have identified an important proinflammatory role for activated intrahepatic V(alpha)14iNKT cells in positively influencing hepatic CCL5 production to promote acute liver inflammation and injury. Therefore, our findings highlight the blockade of CCL5 interaction with a cognate receptor(s) as an important potential strategy to alleviate liver pathology associated with replication-defective adenovirus infection. PMID- 20573838 TI - Regression calibration for classical exposure measurement error in environmental epidemiology studies using multiple local surrogate exposures. AB - Environmental epidemiologic studies are often hierarchical in nature if they estimate individuals' personal exposures using ambient metrics. Local samples are indirect surrogate measures of true local pollutant concentrations which estimate true personal exposures. These ambient metrics include classical-type nondifferential measurement error. The authors simulated subjects' true exposures and their corresponding surrogate exposures as the mean of local samples and assessed the amount of bias attributable to classical and Berkson measurement error on odds ratios, assuming that the logit of risk depends on true individual level exposure. The authors calibrated surrogate exposures using scalar transformation functions based on observed within- and between-locality variances and compared regression-calibrated results with naive results using surrogate exposures. The authors further assessed the performance of regression calibration in the presence of Berkson-type error. Following calibration, bias due to classical-type measurement error, resulting in as much as 50% attenuation in naive regression estimates, was eliminated. Berkson-type error appeared to attenuate logistic regression results less than 1%. This regression calibration method reduces effects of classical measurement error that are typical of epidemiologic studies using multiple local surrogate exposures as indirect surrogate exposures for unobserved individual exposures. Berkson-type error did not alter the performance of regression calibration. This regression calibration method does not require a supplemental validation study to compute an attenuation factor. PMID- 20573835 TI - A single asparagine-linked glycosylation site of the severe acute respiratory syndrome coronavirus spike glycoprotein facilitates inhibition by mannose-binding lectin through multiple mechanisms. AB - Mannose-binding lectin (MBL) is a serum protein that plays an important role in host defenses as an opsonin and through activation of the complement system. The objective of this study was to assess the interactions between MBL and severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein (SARS S). MBL was found to selectively bind to retroviral particles pseudotyped with SARS-S. Unlike several other viral envelopes to which MBL can bind, both recombinant and plasma-derived human MBL directly inhibited SARS-S-mediated viral infection. Moreover, the interaction between MBL and SARS-S blocked viral binding to the C-type lectin, DC-SIGN. Mutagenesis indicated that a single N-linked glycosylation site, N330, was critical for the specific interactions between MBL and SARS-S. Despite the proximity of N330 to the receptor-binding motif of SARS S, MBL did not affect interactions with the ACE2 receptor or cathepsin L-mediated activation of SARS-S-driven membrane fusion. Thus, binding of MBL to SARS-S may interfere with other early pre- or postreceptor-binding events necessary for efficient viral entry. PMID- 20573839 TI - Linking the Iowa Women's Health Study cohort to Medicare data: linkage results and application to hip fracture. AB - This study linked the Iowa Women's Health Study cohort to Medicare administrative data and assessed the value of using Medicare and survey-based sources to study hip fracture incidence. The authors used Social Security number to combine the Iowa Women's Health Study cohort Medicare enrollment and claims data for 1986 2004. Hip fractures were identified from Medicare and follow-up-mail, survey based sources. Estimates of hip fracture incidence after age 65 years and postfracture mortality were compared. The authors were able to match to Medicare 99.2% of the 40,978 Iowa Women's Health Study participants who survived to age 65 years. Although both Medicare and survey-based hip fracture incidence showed the expected positive association with age and negative association with body mass index, hip fracture incidence was considerably underestimated by self-report (2.61 per 1,000 person-years of observation vs. 4.20 per 1,000 person-years of observation from Medicare-based estimates). Similarly, 1-year postfracture mortality was significantly underestimated by survey-based measures (1% vs. 14% for Medicare-based estimates). Medicare data are an outstanding source of health care information to supplement for older cohorts that have identifiers such as Social Security numbers. These data are useful for studying clinically unambiguous and high morbidity and mortality conditions. They enable less-biased collection of health data. PMID- 20573840 TI - A comparative analysis of the Work Ability Index. AB - BACKGROUND: The Work Ability Index (WAI) is a well-established instrument to measure work ability. However, the dimensionality of the WAI remains controversial. AIMS: To identify the dimensionality of the WAI and to investigate dependencies of factors and subscales. METHODS: The sample analysed in this study consisted of 371 subjects of different occupational groups (teachers, office workers, nursery school teachers and managers). The WAI was measured for all subgroups. Psychometric characteristics of the WAI were investigated using factor analyses with different numbers and different patterns of dependency among the factors. Chi-square analysis and the Comparative Fit Index were used to statistically assess fit quality. RESULTS: The group of managers had to be excluded from the analysis as their results were probably overoptimistic due to reporting bias; thus, 324 subjects entered. The one-factor model and an orthogonal two-factor model did not fit the observed correlational structures. A satisfactory fit was obtained using a two-dimensional model with correlated factors. These factors could be interpreted as subjectively estimated work ability and objective health status. Only five of seven items of the WAI could be related unambiguously to one of both factors. CONCLUSIONS: From our study, we conclude that using only the total score of the WAI is not adequate for population analysis of and assessment of work ability to individuals. Instead, the two-dimensional structure of the instrument must be taken into account. PMID- 20573841 TI - Perceptions of occupational injury and illness costs by size of organization. AB - BACKGROUND: Little is known about how organizations perceive and monitor occupational injury and illness costs. AIMS: To explore perceptions of injury and illness costs, the extent to which organizations monitor their impact, attitudes towards this practice and views on using cost information in health and safety campaigns. METHODS: Interviews were conducted with 212 representatives from 49 small- and medium-sized enterprises (SMEs) and 80 large organizations from a range of industry sectors. RESULTS: Health and safety investments were driven by a range of factors, of which cost reduction was only one. Human costs were also considered important. Injuries were perceived to represent a substantial business cost by 10% of respondents from SMEs and 56% of those from large organizations. Most were uncertain about the financial impact of work-related illness. No organizations had attempted to monitor occupational illness costs. Injury costs had been assessed within 3 SMEs and 30 large organizations. Only 12% of SME representatives recognized the benefits of costing health and safety failures and around half were unreceptive to the use of cost information in health and safety promotions. Two-thirds of those from large organizations recognized some benefit in measuring costs, and over three-quarters welcomed the provision of industry specific information. CONCLUSIONS: Provision of information that focuses solely on the economic implications of occupational injury and illness may be of limited value and agencies involved in the promotion of health and safety should incorporate a range of information, taking into account the needs and concerns of different sectors. PMID- 20573842 TI - Fatal occupational injuries in the Arkhangelsk region, Northwest Russia. AB - BACKGROUND: Occupational deaths are used as indicators of occupational safety worldwide. The Arkhangelsk region is among the areas with the highest burden of fatal occupational injuries (FOI) in Russia. AIMS: To describe the occurrence of FOI in the Arkhangelsk region in 1996-2007. METHODS: Data on all FOI reported in the Arkhangelsk region in 1996-2007 were obtained from the State Labour Inspection. Data on the number of employees were collected at the Regional Federal State Statistics Service. The incidence of FOI was calculated by gender, age and economic activity per 100,000 employees. Blood alcohol concentration for all victims was available from the autopsy records. RESULTS: Altogether, there were 734 occupational fatalities during the study period, 94% of them were among men. The incidence of FOI decreased from 18.6 (95% CI 14.6-23.6) in 1996 to 11.7 (95% CI 8.5-16.0) in 2007 among men and from 1.3 (95% CI 0.5-3.2) in 1996 to 0.3 (95% CI 0.1-1.7) in 2006 among women. The agriculture, hunting and forestry sector had the highest incidence of FOI, but they also showed a decrease in FOI from 43.9 (95% CI 32.3-65.3) in 1996 to 20.8 (95% CI 12.0-36.1) in 2007. The highest proportion of FOI occurred on Tuesdays (17%) and Wednesdays (18%). Thirty two of the victims had blood alcohol concentration >0.5 per thousand. CONCLUSIONS: The incidence of FOI in the Arkhangelsk region decreased from 1996 to 2007, but remains high and varies by gender, age and economic activity over time. PMID- 20573843 TI - Accidental poisoning with detomidine and butorphanol. AB - This is a case report concerning a veterinarian who spilled detomidine and butorphanol on dermatitic hands while sedating a horse. This resulted in acute poisoning from which the patient spontaneously recovered with supportive management. Veterinarians often suffer from occupational dermatitis and handle strong sedatives with no gloves while working around unpredictable animals. Thus, this group is at risk of accidental self-poisoning from this method. PMID- 20573844 TI - Bladder cancer risk in painters. PMID- 20573845 TI - Predictors of race-day jockey falls in flat racing in Australia. AB - OBJECTIVES: Riding thoroughbred racehorses is a hazardous occupation. In this study, we investigated risk factors associated with falls by licensed thoroughbred racing jockeys participating in flat races conducted in Australia. METHODS: Data on race-day falls were extracted from stewards' reports. Denominator data were provided by Racing Information Services Australia on races conducted in Australia from August 2002 until July 2006. Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses were stratified by race grade (maiden, class, open/restricted). RESULTS: In multivariable analyses, factors associated with falls were female sex of jockey (IRR 1.11; 95% CI 1.00 to 1.23), being an apprentice jockey (IRR 1.51; 95% CI 1.39 to 1.63), being an amateur jockey (IRR 1.44; 95% CI 1.11 to 1.86), drier tracks (p<0.001), younger horse age (p<0.001), shorter race distance (p<0.001), lower field size (p=0.013) and lower race grade (p<0.001). The IRRs for five factors associated with falls differed by category of race grade: those for apprentice jockey (interaction p=0.003), higher prize money (interaction p<0.001) and shorter race distance (interaction p=0.041) were greater in lower race grades, while those for fewer previous rides this meeting (interaction p=0.027) and drier track rating (interaction p=0.035) were greater in higher race grades. Female jockeys had a significantly higher incidence of falls when riding horses under 4 years of age in open and restricted races (interaction p=0.038), and the effects of lower field size in maiden races, and of shorter races, were more pronounced for falls occurring before the race. CONCLUSIONS: We identified a range of factors associated with falls to thoroughbred racing jockeys riding in flat races that adds to the evidence base for formulating strategies to improve occupational health and safety standards in the thoroughbred racing industry. PMID- 20573846 TI - Work-related mortality in England and Wales, 1979-2000. AB - BACKGROUND: To explore time trends in deaths attributable to work in England and Wales, and identify priorities for prevention, we conducted a proportional analysis of mortality by occupation over a 22-year period. METHODS: Analysis was based on deaths in men aged 20-74 years during 1979-1980 and 1982-2000 with a recorded occupation. Proportional mortality ratios, standardised for age and social class, were calculated for pre-specified combinations of occupation and cause of death, for which excess mortality could reasonably be attributed to work. Differences between observed and expected numbers of deaths by cause and occupation were expressed as annual excess death rates. RESULTS: Mortality attributable to work declined substantially over the period of study, with total excess death rates of 733.2 per year during 1979-1990 and 471.7 per year during 1991-2000. The largest contributing hazards were chronic obstructive pulmonary disease and pneumoconiosis in coal miners, pleural cancer from asbestos, and motor vehicle accidents in lorry drivers. In contrast to most other hazards, there was no clear decline in excess mortality attributable to asbestos, or in deaths from sino-nasal cancer associated with exposure to wood dust. CONCLUSIONS: The overall decline in mortality attributable to work is likely to reflect reduced employment in more hazardous occupations, as well as improvements in working conditions. It is imperative to ensure that occupational exposures to asbestos and wood dust are now adequately controlled. Further research is needed on accidents involving lorries with the aim of developing more effective strategies for the prevention of injury. PMID- 20573847 TI - How valid is a short measure of effort-reward imbalance at work? A replication study from Sweden. AB - OBJECTIVES: There is an urgent need for validated measures of health-adverse psychosocial work environments. We tested the validity of a newly developed short version of the original questionnaire measuring effort-reward imbalance at work (ERI). METHODS: The study sample comprised working men and women (n=4771) participating in the Swedish Longitudinal Occupational Survey of Health (SLOSH), a nationally representative longitudinal cohort study, in 2006 and 2008. Structural equation modelling was applied to test factorial validity, using the ERI scales. Furthermore, criterion validity was explored with two prospectively assessed health indicators, poor self-reported health and depressive symptoms. Results are based on logistic and linear regression analyses, with appropriate confounder control. RESULTS: The short version of the ERI questionnaire (16 items) provides satisfactory psychometric properties (internal consistency of scales, confirmatory factor analysis with a good model fit of the data with the theoretical structure). All scales, and the effort-reward ratio, were prospectively associated with an increased risk of poor general self-rated health and depressive symptoms, indicating satisfactory criterion validity. CONCLUSION: This short version of the ERI questionnaire provides a psychometrically useful tool for epidemiological studies focused on the health-adverse effects of work and employment in the context of a globalised economy. PMID- 20573848 TI - Calculation of the benchmark duration of shift work associated with the development of impaired glucose metabolism: a 14-year cohort study on 7104 male workers. AB - OBJECTIVES: The aim of this study was to calculate the benchmark doses (BMD) and their 95% lower confidence boundary (BMDL) for the threshold number of years of shift work associated with a relative increase in haemoglobin A1c (HbA(1c)), an index of glucose metabolism. METHODS: A 14-year prospective cohort study was conducted in male workers at a Japanese steel company (n=7104) who had received annual health check-ups between 1991 and 2005. The endpoints were either a 10%, 15%, 20%, 25% or 30% increase in HbA(1c) levels during the observation period, compared to HbA(1c) at entry to the study. The associations between years of shift work and increases in HbA(1c) were investigated using pooled logistic regression, adjusted for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habits, smoking habits and habitual exercise. RESULTS: The BMDL/BMD for years of shift work were calculated using benchmark responses (BMRs) of 5% or 10% and parameters for duration of shift work and other covariates. Assuming a mean age of 53 years in workers aged 50 years or older, the BMDL/BMD for years of shift work with a BMR of 5% were 17.8/23.9 (> or = 15%), 15.7/18.7 (> or = 20%), 18.9/22.7 (> or = 25%) and 25.2/31.7 (> or = 30%). With a BMR of 10%, the respective values were 29.5/39.7 (> or = 15%), 24.3/28.9 (> or = 20%), 27.3/32.7 (> or = 25%) and 34.1/42.9 (> or = 30%). CONCLUSION: These results suggest that special attention should be paid to middle-aged workers whose years of shift work exceeds these threshold times. PMID- 20573849 TI - Tinnitus and mobile phone use. AB - OBJECTIVES: The mechanisms that produce tinnitus are not fully understood. While tinnitus can be associated with diseases and disorders of the ear, retrocochlear diseases and vascular pathologies, there are few known risk factors for tinnitus apart from these conditions. There is anecdotal evidence of an link between mobile phone use and tinnitus, but so far there have been no systematic investigations into this possible association. METHODS: 100 consecutive patients presenting with tinnitus were enrolled in an individually matched case-control study. For each case a control subject was randomly selected from visiting outpatients matched for sex and age. The patient's history was obtained and clinical examinations were conducted to exclude patients with known underlying causes of tinnitus. Mobile phone use was assessed based on the Interphone Study protocol. ORs were computed by conditional logistic regression with years of education and living in an urban area as covariates. RESULTS: Mobile phone use up to the index date (onset of tinnitus) on the same side as the tinnitus did not have significantly elevated ORs for regular use and intensity or for cumulative hours of use. The risk estimate was significantly elevated for prolonged use (>=4 years) of a mobile phone (OR 1.95; CI 1.00 to 3.80). CONCLUSIONS: Mobile phone use should be included in future investigations as a potential risk factor for developing tinnitus. PMID- 20573850 TI - Gain, but what, how much and at what cost? PMID- 20573851 TI - Sorafenib-induced erythema multiforme for metastatic renal cell carcinoma. PMID- 20573852 TI - High concordance of BRAF status between primary colorectal tumours and related metastatic sites: implications for clinical practice. PMID- 20573853 TI - Effectiveness of a 'hunter' virus in controlling human immunodeficiency virus type 1 infection. AB - Engineered therapeutic viruses provide an alternative method for treating infectious diseases, and mathematical models can clarify the system's dynamics underlying this type of therapy. In particular, this study developed models to evaluate the potential to contain human immunodeficiency virus type 1 (HIV-1) infection using a genetically engineered 'hunter' virus that kills HIV-1-infected cells. First, we constructed a novel model for understanding the progression of HIV infection that predicted the loss of the immune system's CD4(+) T cells across time. Subsequently, it determined the effects of introducing hunter viruses in restoring cell population. The model implemented direct and indirect mechanisms by which HIV-1 may cause cell depletion and an immune response. Results suggest that the slow progression of HIV infection may result from a slowly decaying CTL immune response, leading to a limited but constant removal of uninfected CD4 resting cells through apoptosis - and from resting cell proliferation that reduces the rate of cell depletion over time. Importantly, results show that the hunter virus does restrain HIV infection and has the potential to allow major cell recovery to 'functional' levels. Further, the hunter virus persisted at a reduced HIV load and was effective either early or late in the infection. This study indicates that hunter viruses may halt the progression of the HIV infection by restoring and sustaining high CD4(+) T-cell levels. PMID- 20573854 TI - Vaccination against a hit-and-run viral cancer. AB - Cancers with viral aetiologies can potentially be prevented by antiviral vaccines. Therefore, it is important to understand how viral infections and cancers might be linked. Some cancers frequently carry gammaherpesvirus genomes. However, they generally express the same viral genes as non-transformed cells, and differ mainly in also carrying oncogenic host mutations. Infection, therefore, seems to play a triggering or accessory role in disease. The hit-and run hypothesis proposes that cumulative host mutations can allow viral genomes to be lost entirely, such that cancers remaining virus-positive represent only a fraction of those to which infection contributes. This would have considerable implications for disease control. However, the hit-and-run hypothesis has so far lacked experimental support. Here, we tested it by using Cre-lox recombination to trigger transforming mutations in virus-infected cells. Thus, 'floxed' oncogene mice were infected with Cre recombinase-positive murid herpesvirus-4 (MuHV-4). The emerging cancers showed the expected genetic changes but, by the time of presentation, almost all lacked viral genomes. Vaccination with a non-persistent MuHV-4 mutant nonetheless conferred complete protection. Equivalent human gammaherpesvirus vaccines could therefore potentially prevent not only viral genome-positive cancers, but possibly also some cancers less suspected of a viral origin because of viral genome loss. PMID- 20573855 TI - Use of a preclinical test in the control of classical scrapie. AB - Scrapie control in Great Britain (GB) was originally based on the National Scrapie Plan's Ram Genotyping scheme aimed at reducing the susceptibility of the national flock. The current official strategy to control scrapie in the national flock involves culling susceptible genotypes in individual, known affected flocks (compulsory scrapie flock scheme or CSFS). However, the recent development of preclinical test candidates means that a strategy based on disease detection may now be feasible. Here, a deterministic within-flock model was used to demonstrate that only large flocks with many home-bred ewes are likely to be a significant risk for flock-to-flock transmission of scrapie. For most other flocks, it was found that the CSFS could be replaced by a strategy using a currently available live test without excessive risk to other farmers, even if the proportion of susceptible genotypes in the flock is unusually large. Even for flocks that represent a high risk of harbouring a high prevalence of infection, there would be limited probability of onward transmission if scrapie is detected soon after disease introduction (typically less than 5 years). However, if detection of disease is delayed, the existing CSFS strategy may be the most appropriate control measure in these cases. PMID- 20573856 TI - Associations between MHC genes and Puumala virus infection in Myodes glareolus are detected in wild populations, but not from experimental infection data. AB - We analysed the influence of MHC class II Dqa and Drb genes on Puumala virus (PUUV) infection in bank voles (Myodes glareolus). We considered voles sampled in five European localities or derived from a previous experiment that showed variable infection success of PUUV. The genetic variation observed in the Dqa and Drb genes was assessed by using single-strand conformation polymorphism and pyrosequencing methods, respectively. Patterns were compared with those obtained from 13 microsatellites. We revealed significant genetic differentiation between PUUV-seronegative and -seropositive bank voles sampled in wild populations, at the Drb gene only. The absence of genetic differentiation observed at neutral microsatellites confirmed the important role of selective pressures in shaping these Drb patterns. Also, we found no significant associations between infection success and MHC alleles among laboratory-colonized bank voles, which is explained by a loss of genetic variability that occurred during the captivity of these voles. PMID- 20573857 TI - Genomic expression profiling in lymph nodes with lymphoid depletion from porcine circovirus 2-infected pigs. AB - Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated disease, such as post-weaning multisystemic wasting syndrome, which involves lymphocyte depletion. However, little is known about the molecular mechanisms of lymphoid depletion. To gain insight into the interaction between virus and host cells, microarrays were used to analyse changes in genomic expression in lymph nodes following PCV2 infection of pigs, together with negative controls. Total RNA was subjected to microarray analysis with an Affymetrix Porcine Genome Array GeneChip. Of the 23,256 pig genes arrayed on a chip, 160 genes showed altered expression after infection (upregulated, 64; downregulated, 96). The altered genomic expression of 18 selected genes was confirmed by quantitative real-time PCR. The expression changes of numerous genes involved in innate immune defence (TLR1, CD14 and CD180), immunosuppressed responses (FGL2 and GPNMB), pro-inflammatory signals (galectin-3) and fasting processes (ANGPTL-4) indicate that PCV2 has developed an intricate mechanism to cause immunosuppression, inflammatory cell infiltration and weight loss in pigs. The results of this study provide a basis for understanding the molecular pathogenesis of PCV2 infection. PMID- 20573858 TI - A functional calcium-transporting ATPase encoded by chlorella viruses. AB - Calcium-transporting ATPases (Ca(2+) pumps) are major players in maintaining calcium homeostasis in the cell and have been detected in all cellular organisms. Here, we report the identification of two putative Ca(2+) pumps, M535L and C785L, encoded by chlorella viruses MT325 and AR158, respectively, and the functional characterization of M535L. Phylogenetic and sequence analyses place the viral proteins in group IIB of P-type ATPases even though they lack a typical feature of this class, a calmodulin-binding domain. A Ca(2+) pump gene is present in 45 of 47 viruses tested and is transcribed during virus infection. Complementation analysis of the triple yeast mutant K616 confirmed that M535L transports calcium ions and, unusually for group IIB pumps, also manganese ions. In vitro assays show basal ATPase activity. This activity is inhibited by vanadate, but, unlike that of other Ca(2+) pumps, is not significantly stimulated by either calcium or manganese. The enzyme forms a (32)P-phosphorylated intermediate, which is inhibited by vanadate and not stimulated by the transported substrate Ca(2+), thus confirming the peculiar properties of this viral pump. To our knowledge this is the first report of a functional P-type Ca(2+)-transporting ATPase encoded by a virus. PMID- 20573859 TI - Prevalence and genetic diversity of adeno-associated viruses in bats from China. AB - Bats are increasingly being recognized as important natural reservoirs of different viruses. Adeno-associated viruses (AAVs) are widely distributed in primates and their distribution in bats is unknown. In this study, a total of 370 faecal swab samples from 19 bat species were collected from various provinces of China and examined for the presence of AAVs. The mean prevalence rate was 22.4% (83 positives out of 370 samples), ranging from 10 to 38.9% among different bat species. The genome sequence spanning the entire rep-cap ORFs was determined from one chosen AAV-positive sample (designated BtAAV-YNM). Phylogenetic analysis of the entire rep-cap ORF coding sequences suggested that BtAAV-YNM is relatively distant to known primate AAVs, but phylogenetically closer to porcine AAV strain Po3. Further analysis of the partial cap ORF sequences of bat AAV samples (n=49) revealed a remarkably large genetic diversity, with an average pairwise nucleotide identity of only 84.3%. Co-presence of multiple distinctive genotypes of bat AAV within an individual sample was also observed. These results demonstrated that diverse AAVs might be widely distributed in bat populations. PMID- 20573860 TI - Human astrovirus infection in a patient with new-onset celiac disease. AB - Many diseases with unknown etiology may be caused by unidentified viruses. Sequence-independent amplification revealed a new astrovirus, similar to VA1, in a 4-year-old male diagnosed with celiac disease. This expands the geographic range of this virus to include Europe and may associate astrovirus infection with the onset of celiac disease. PMID- 20573861 TI - Emergence and characterization of Salmonella enterica serovar Typhimurium phage type DT191a. AB - The emergence of a previously undefined phage type of Salmonella enterica serovar Typhimurium, designated DT191a, occurred in England and Wales in July 2008. The new strain exhibits a number of distinctive phenotypic and genotypic features. This report provides the tools necessary to track S. Typhimurium DT191a globally. PMID- 20573863 TI - Evaluation of the integrated database network system (IDNS) SmartGene software for analysis of 16S rRNA gene sequences for identification of Nocardia species. AB - 16S rRNA gene sequences of 102 Nocardia isolates were analyzed using the Integrated Database Network System (IDNS) SmartGene centroid database. A total of 76% of the isolates were correctly identified. Discordant identifications were due to inadequate centroid length (3 species), inaccurate or insufficient entries in the public databases (5 species), and heterogeneous sequences among members of a species (1 species). PMID- 20573862 TI - Clinical performance of the PreTect HPV-Proofer E6/E7 mRNA assay in comparison with that of the Hybrid Capture 2 test for identification of women at risk of cervical cancer. AB - Human papillomavirus (HPV) DNA testing has a higher clinical sensitivity than cytology for the detection of high-grade cervical intraepithelial neoplasia or worse (CIN 2+). However, an improvement in specificity would be desirable. As malignant transformation is induced by HPV E6/E7 oncogenes, detection of E6/E7 oncogene activity may improve specificity and be more predictive of cervical cancer risk. The PreTect HPV-Proofer assay (Proofer; Norchip) detects E6/E7 mRNA transcripts from HPV types 16, 18, 31, 33, and 45 with simultaneous genotype specific identification. The clinical performance of this assay was assessed in a cross-sectional study of women referred for colposcopy in comparison with the Hybrid Capture 2 (HC2; Qiagen) test, which detects DNA of 13 high-risk oncogenic HPV types collectively. Cervical specimens were collected in PreservCyt, and cytology was performed using the ThinPrep method (Hologic). The samples were processed for HPV detection with Proofer and HC2 and genotyping with the Linear Array method (Roche Molecular Systems). Histology-confirmed CIN 2+ served as the disease endpoint to assess the clinical performance of the tests. A total of 1,551 women were studied, and of these, 402 (25.9%) were diagnosed with CIN 2+ on histology. The Proofer assay showed a sensitivity of 78.1% (95% confidence interval [CI], 74.1 to 82.1) versus 95.8% (95% CI, 93.8 to 97.8) for HC2 (P < 0.05) and a specificity of 75.5% (95% CI, 73.0 to 78.0) versus 39.6% (95% CI, 36.8 to 42.4), respectively (P < 0.05). The lower sensitivity and higher specificity of Proofer for detection of CIN 2+ can be attributed to the fact that this test detects the expression of E6/E7 genes beyond a threshold from a limited number of oncogenic HPV types. In conclusion, Proofer is more specific than HC2 in identifying women with CIN 2+ but has a lower sensitivity. PMID- 20573864 TI - Evaluation of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test and identification of rare polymorphisms potentially affecting assay performance. AB - We evaluated the FDA-approved Roche Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 viral load assay for sensitivity, reproducibility, linearity, HIV-1 subtype detection, and correlation to the Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor). The limit of detection calculated by probit analysis was 23.8 copies/ml using the 2nd International WHO Standard and 30.8 copies/ml using Viral Quality Assurance (VQA) standard material. Serial dilutions of six patient samples were used to determine inter- and intra-assay reproducibility and linearity, which were very good (<8% coefficient of variation [CV]; between approximately 1.7 and 7.0 log(10) copies/ml). Subtype detection was evaluated in the CAP/CTM, Amplicor, and Bayer Versant HIV-1 bDNA 3.0 (Versant) assays using a commercially available panel. Versant averaged 0.829 log(10) copies/ml lower than CAP/CTM and Amplicor averaged 0.427 log(10) copies/ml lower than CAP/CTM for the subtype panel. Correlation with samples previously tested by Amplicor was excellent (R(2) = 0.884; average difference [Amplicor value minus CAP/CTM value], 0.008 log(10) copies/ml). Of the 305 HIV samples tested, 7 samples generated CAP/CTM titers between 1.0 and 2.75 log(10) copies/ml lower than those for Amplicor. Three of these samples revealed primer and probe mismatches that could account for the discrepancies. Otherwise, the CAP/CTM assay exhibits excellent sensitivity, dynamic range, reproducibility, and correlation with Amplicor in an automated format. PMID- 20573865 TI - Pseudomonas aeruginosa outbreak linked to mineral water bottles in a neonatal intensive care unit: fast typing by use of high-resolution melting analysis of a variable-number tandem-repeat locus. AB - Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections in intensive care units. Determining a system of typing that is discriminatory is essential for epidemiological surveillance of P. aeruginosa. We developed a method for the typing of Pseudomonas aeruginosa, namely, multiple locus variable-number tandem-repeat (VNTR) typing with high-resolution melting analysis (HRMA). The technology was used to genotype a collection of 43 environmental and clinical strains isolated during an outbreak in a neonatal intensive care unit (NICU) that we report. Nineteen strains isolated in other departments or outside the hospital were also tested. The genetic diversity of this collection was determined using VNTR-HRMA, with amplified fragment length polymorphism (AFLP) analysis as a reference. Twenty-five and 28 genotypes were identified, respectively, and both techniques produced congruent data. VNTR-HRMA established clonal relationships between the strains of P. aeruginosa isolated during the outbreak in the NICU and proved, for the first time, the role of mineral water as the inoculum source. VNTR typing with one primer pair in association with HRMA is highly reproducible and discriminative, easily portable among laboratories, fast, and inexpensive, and it demonstrated excellent typeability in this study. VNTR-HRMA represents a promising tool for the molecular surveillance of P. aeruginosa and perhaps for molecular epidemiologic analysis of other hospital infections. PMID- 20573866 TI - Cross-reactivity of current serogroup 6 factor sera from Statens Serum Institut with the recently described pneumococcal serotype 6d. PMID- 20573867 TI - Higher prevalence of pharyngeal than nasal Staphylococcus aureus carriage in pediatric intensive care units. AB - Sensitive detection of Staphylococcus aureus colonization is important for epidemiologic studies, infection control, and decolonization measures. We examined the sensitivity of nasal and pharyngeal sampling for S. aureus colonization in 331 children admitted to intensive care units. Pharyngeal screening was more sensitive than nasal screening (92.6% versus 63.1%, P < 0.0001). PMID- 20573868 TI - Evaluation of the MTBDRsl test for detection of second-line-drug resistance in Mycobacterium tuberculosis. AB - The MTBDRsl assay (Hain Lifescience GmbH, Germany) is a new line probe assay for the detection of extensively drug-resistant tuberculosis (XDR TB). The test simultaneously detects resistance to ethambutol, aminoglycosides/cyclic peptides, and fluoroquinolones through detection of mutations in the relevant genes. The assay format is identical to the MTBDR Hain assay. The assay was evaluated for the detection of second-line-drug resistance in Vietnamese isolates using two sample sets from the microbiology department of Pham Ngoc Thach Hospital, Ho Chi Minh City, Viet Nam, with existing conventional phenotypic drug susceptibility results for second-line drugs: 41 consecutive fluoroquinolone-resistant isolates and 21 consecutive multidrug-resistant but fluoroquinolone-sensitive isolates. The sensitivity for detection of fluoroquinolone resistance was 75.6% (31/41) (95% confidence interval [95% CI], 59.7% to 87.6%), and for kanamycin resistance, the sensitivity was 100% (5/5) (95% CI, 47.8% to 100%). The sensitivity of the test for detection of ethambutol resistance was low, consistent with previous reports, at 64.2% (34/53) (95% CI, 49.8% to 76.9%). The specificity of the test was 100% for all three drugs. These data suggest that the MTBDRsl assay is a rapid, specific test for the detection of XDR TB but should not be used exclusively to "rule out" second-line-drug resistance. Further operational evaluation is required and should be integrated with evaluations of the MTBDR test. PMID- 20573869 TI - New assessment of bovine tuberculosis risk factors in Belgium based on nationwide molecular epidemiology. AB - This assessment aimed to elaborate a statistical nationwide model for analyzing the space-time dynamics of bovine tuberculosis in search of potential risk factors that could be used to better target surveillance measures. A database comprising Mycobacterium bovis molecular profiles from all isolates obtained from Belgian outbreaks during the 1995-to-2006 period (n = 415) allowed the identification of a predominant spoligotype (SB0162). Various databases compiling 49 parameters to be tested were queried using a multiple stepwise logistic regression to assess bovine tuberculosis risk factors. Two isolate datasets were analyzed: the first included all Mycobacterium bovis isolates, while the second included only data related to the SB0162 type strain. When all Mycobacterium bovis isolates were included in the model, several risk factors were identified: history of bovine tuberculosis in the herd (P < 0.001), proximity of an outbreak (P < 0.001), cattle density (P < 0.001), and annual amplitude of mean middle infrared temperature (P < 0.001). The approach restricted to the predominant SB0162 type strain additionally highlighted the proportion of movements from an infected area during the current year as a main risk factor (P = 0.009). This study identified several risk factors for bovine tuberculosis in cattle, highlighted the usefulness of molecular typing in the study of bovine tuberculosis epidemiology, and suggests a difference of behavior for the predominant type strain. It also emphasizes the role of animals' movements in the transmission of the disease and supports the importance of controlling trade movements. PMID- 20573870 TI - Molecular identification of Entamoeba spp. in captive nonhuman primates. AB - This study describes the molecular identification of 520 Entamoeba-positive fecal samples from a large and diverse population of captive nonhuman primates (NHP). The results revealed the presence of Entamoeba histolytica (NHP variant only), E. dispar, E. moshkovskii, E. hartmanni, E. coli, and E. polecki-like organisms. PMID- 20573871 TI - Distribution of emm types and genetic characterization of the mgc locus in group G Streptococcus dysgalactiae subsp. equisimilis from a hospital in northern Taiwan. AB - A total of 274 Streptococcus dysgalactiae subsp. equisimilis isolates was analyzed by emm typing and by determining the organization of their mgrC loci. Three of the most frequent emm types were stG485.0 (45/274, 16.4%), stG6.1 (43/274, 15.7%), and stC839.0 (32/274, 11.7%), in decreasing order. The cpdB positive mgrC locus appears to be predominant in some emm types. PMID- 20573872 TI - Improving HIV-2 detection by a combination of serological and nucleic acid amplification test assays. AB - The ability to detect HIV-2 and to discriminate between HIV-1 and HIV-2 infections was evaluated in 46 serum samples from Guinea-Bissau (GB) and Guinea Conakry (GC) using serological tests and commercial (HIV-1) and in-house (HIV-2) real-time PCR assays. Samples were first identified as HIV-2 positive by Genie I/II assay in GB and GC. HIV positivity was detected in 44 of 46 samples by all screening and confirmatory assays. A diagnostic strategy based on Inno-LIA and HIV-1/2 RNA detection assays allowed accurate discrimination between HIV-1 and HIV-2 in 84% of single infections and confirmed 32% of double infections. In samples with double reactivity in the Inno-LIA test and no detection of both genomes, cross-reactivity likely hampered the identification of true double infections. In conclusion, the implementation of a diagnostic strategy, based on multiple specific serological tests and highly sensitive quantitative PCR assays, is recommended to ensure accurate HIV-2 diagnosis and appropriate therapy for individuals from areas in which the virus is endemic. PMID- 20573873 TI - Systematic internal transcribed spacer sequence analysis for identification of clinical mold isolates in diagnostic mycology: a 5-year study. AB - The implementation of internal transcribed spacer (ITS) sequencing for routine identification of molds in the diagnostic mycology laboratory was analyzed in a 5 year study. All mold isolates (n = 6,900) recovered in our laboratory from 2005 to 2009 were included in this study. According to a defined work flow, which in addition to troublesome phenotypic identification takes clinical relevance into account, 233 isolates were subjected to ITS sequence analysis. Sequencing resulted in successful identification for 78.6% of the analyzed isolates (57.1% at species level, 21.5% at genus level). In comparison, extended in-depth phenotypic characterization of the isolates subjected to sequencing achieved taxonomic assignment for 47.6% of these, with a mere 13.3% at species level. Optimization of DNA extraction further improved the efficacy of molecular identification. This study is the first of its kind to testify to the systematic implementation of sequence-based identification procedures in the routine workup of mold isolates in the diagnostic mycology laboratory. PMID- 20573874 TI - Peptide nucleic acid array for detection of point mutations in hepatitis B virus associated with antiviral resistance. AB - The detection of antiviral-resistant hepatitis B virus (HBV) mutations is important for monitoring the response to treatment and for effective treatment decisions. We have developed an array using peptide nucleic acid (PNA) probes to detect point mutations in HBV associated with antiviral resistance. PNA probes were designed to detect mutations associated with resistance to lamivudine, adefovir, and entecavir. The PNA array assay was sensitive enough to detect 10(2) copies/ml. The PNA array assay was able to detect mutants present in more than 5% of the virus population when the total HBV DNA concentration was greater than 10(4) copies/ml. We analyzed a total of 68 clinical samples by this assay and validated its usefulness by comparing results to those of the sequencing method. The PNA array correctly identified viral mutants and has high concordance (98.3%) with direct sequencing in detecting antiviral-resistant mutations. Our results showed that the PNA array is a rapid, sensitive, and easily applicable assay for the detection of antiviral-resistant mutation in HBV. Thus, the PNA array is a useful and powerful diagnostic tool for the detection of point mutations or polymorphisms. PMID- 20573875 TI - First case of postaneurysmal prosthetic vascular infection due to a nonsuperantigenic Yersinia pseudotuberculosis strain. AB - Among Yersinia spp., Y. enterocolitica is the species most frequently isolated from infected aneurysms. This report describes the first case of postaneurysmal prosthetic vascular infection due to a superantigen-negative Yersinia pseudotuberculosis strain, showing a potential affinity of this species for endovascular tissue. PMID- 20573876 TI - Utilization of the QuantiFERON-TB Gold test in a two-step process with the tuberculin skin test to evaluate health care workers for latent tuberculosis. AB - A cost analysis of combining a tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT-GT) to detect latent tuberculosis in newly hired health care workers was performed. An approximately 50% reduction in the cost of additional care was realized when workers with positive TST results were subsequently screened using the QFT-GT. PMID- 20573877 TI - First report of septic arthritis caused by Klebsiella oxytoca. AB - Klebsiella oxytoca is known to be a pathogen in immunodeficient adults and children. Here we report the first case of a K. oxytoca infection associated with spontaneous arthritis of the knee in a child with no history of immunosuppressive therapy or previous bacterial infections. Despite an initial antibiotic treatment failure, a second treatment led to a cure of the infection with no joint sequelae. PMID- 20573878 TI - Low specificities of HIV diagnostic tests caused by Trypanosoma brucei gambiense sleeping sickness. AB - The accuracy of diagnostic tests for HIV in patients with tropical infections is poorly documented. Human African trypanosomiasis (HAT) is characterized by a polyclonal B-cell activation, constituting a risk for false-positive reactions to diagnostic tests, including HIV tests. A retrospective study of the accuracy of HIV diagnostic tests was performed with 360 human African HAT patients infected with Trypanosoma brucei gambiense before treatment and 163 T. b. gambiense infected patients 2 years after successful treatment in Mbuji Mayi, East Kasai, Democratic Republic of the Congo. The sensitivities, specificities, and positive predictive values (PPVs) of individual tests and algorithms consisting of 3 rapid tests were determined. The sensitivity of all tests was 100% (11/11). The low specificity (96.3%, 335/348) and PPV (45.8%, 11/24) of a classical seroconfirmation strategy (Vironostika enzyme-linked immunosorbent assay [ELISA] followed by line immunoassay) complicated the determination of HIV status, which had to be determined by PCR. The specificities of the rapid diagnostic tests were 39.1% for Determine (136/348); 85.3 to 92.8% (297/348 to 323/348) for Vikia, ImmunoFlow, DoubleCheck, and Bioline; and 96.6 to 98.3% (336/348 to 342/348) for Uni-Gold, OraQuick, and Stat-Pak. The specificity of Vironostika was 67.5% (235/348). PPVs ranged between 4.9 and 64.7%. Combining 3 different rapid tests resulted in specificities of 98.3 to 100% (342/348 to 348/348) and PPVs of 64.7 to 100% (11/17 to 11/11). For cured HAT patients, specificities were significantly higher for Vironostika, Determine, Uni-Gold, and ImmunoFlow. T. b. gambiense infection decreases the specificities of antibody detection tests for HIV diagnosis. Unless tests have been validated for interference with HAT, HIV diagnosis using classical algorithms in untreated HAT patients should be avoided. Specific, validated combinations of 3 HIV rapid tests can increase specificity. PMID- 20573879 TI - Evaluation of a commercial SD dengue virus NS1 antigen capture enzyme-linked immunosorbent assay kit for early diagnosis of dengue virus infection. AB - Early definitive diagnosis of dengue virus infection may help in the timely management of dengue virus infection. We evaluated the Standard Diagnostics (SD, South Korea) dengue virus nonstructural protein NS1 antigen enzyme-linked immunosorbent assay (SD dengue NS1 Ag ELISA) for the detection of dengue virus NS1 antigen in patients' sera, using a total of 399 serum samples in a comparison with real-time reverse transcription (RT)-PCR, an in-house IgM capture (MAC) ELISA, and a hemagglutination inhibition (HI) assay. Of the 320 dengue sera, 205 (64%) tested positive for NS1 antigen compared to 300 (93.75%) by either MAC ELISA or RT-PCR, 161 (50.31%) by RT-PCR, and 226 (70.36%) by MAC-ELISA only. The assay was able to detect NS1 antigen in convalescent-phase sera until day 14 of infection. The NS1 detection rate is inversely proportional while the IgM detection rate is directly proportional to the presence of IgG antibodies. The overall sensitivity and specificity of the SD dengue NS1 Ag ELISA in the detection of "confirmed dengue virus" sera are 76.76% and 98.31%, respectively. This suggests that the SD kit is highly specific and sensitive for the detection of NS1 antigen. However, caution is needed when the kit is used as a single assay, as detection in samples that contained the virus was only about 81.97%. Combining this assay with an IgM and/or IgG assay will increase the sensitivity of detection, especially in areas with a higher prevalence of secondary dengue virus infections. PMID- 20573880 TI - Characterization of anti-Salmonella enterica serotype Typhi antibody responses in bacteremic Bangladeshi patients by an immunoaffinity proteomics-based technology. AB - Salmonella enterica serotype Typhi is the cause of typhoid fever and a human restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays. PMID- 20573881 TI - Recombinant diabody-based immunocapture enzyme-linked immunosorbent assay for quantification of rabies virus glycoprotein. AB - The potency of rabies vaccines, determined using the NIH mouse protection test, can be directly correlated to the amount of rabies virus glycoprotein (RV GP) present in the vaccine. In an effort to develop a simple and sensitive enzyme linked immunosorbent assay (ELISA) using recombinant diabody for quantification of RV GP, the variable heavy (V(H)) and light chain (V(L)) domains of an RV GP specific human monoclonal antibody (MAb) secreted by a human x mouse heterohybridoma (human MAb R16E5) was amplified, linked using splicing by overlap extension PCR (SOE PCR), and expressed as a recombinant diabody (D06) in the pET28a bacterial expression system. The diabody D06 was purified by immobilized metal affinity chromatography on a nickel-nitrilotriacetic acid (NTA) agarose column and characterized. The purified diabody was used in combination with a well-characterized RV GP-specific mouse MAb, M5B4, to develop an immunocapture ELISA (IC-ELISA) for the quantification of RV GP in human rabies vaccine preparations. The maximum detection limit of the IC-ELISA using the M5B4-D06 combination was up to 31.25 ng/ml of RV GP. The specificity of the diabody was established by its nonreactivity toward other human viral antigens as determined by ELISA and toward RV GP as determined by immunoblot transfer assay and competitive ELISA with the parent human MAb R16E5 and MAb M5B4. The adjusted r(2) value obtained by the regression through the origin model was 0.902, and the equation for predicted potency values for M5B4-D06-based IC-ELISA and MAb M5B4 IC ELISA were 0.5651x and 0.8044x, respectively, where x is the estimate of RV GP from the IC-ELISA in micrograms. Analysis of variance (ANOVA) results showed the estimates of the two methods differed significantly (P < 0.001), while the predicted potencies by the two tests did not differ significantly (P > 0.05). The IC-ELISA can be readily adapted to measure the RV GP content in purified antigen, and a vaccine can be formulated based on the estimated GP. PMID- 20573882 TI - Aplysia cell adhesion molecule and a novel protein kinase C activity in the postsynaptic neuron are required for presynaptic growth and initial formation of specific synapses. AB - To explore the role of both Aplysia cell adhesion molecule (ApCAM) and activity of specific protein kinase C (PKC) isoforms in the initial formation of sensory neuron synapses with specific postsynaptic targets (L7 but not L11), we examined presynaptic growth, initial synapse formation, and the expression of the presynaptic neuropeptide sensorin following cell-specific reduction of ApCAM or of a novel PKC activity. Synapse formation between sensory neurons and L7 begins by 3 h after plating and is accompanied by a rapid accumulation of a novel PKC to sites of synaptic interaction. Reducing ApCAM expression specifically from the surface of L7 blocks presynaptic growth and initial synapse formation, target induced increase of sensorin in sensory neuron cell bodies and the rapid accumulation of the novel PKC to sites of interaction. Selective blockade of the novel PKC activity in L7, but not in sensory neurons, with injection of a dominant negative construct that interferes with the novel PKC activity, produces the same actions as downregulating ApCAM; blockade of presynaptic growth and initial synapse formation, and the target-induced increase of sensorin in sensory neuron cell bodies. The results indicate that signals initiated by postsynaptic cell adhesion molecule ApCAM coupled with the activation of a novel PKC in the appropriate postsynaptic neuron produce the retrograde signals required for presynaptic growth associated with initial synapse formation, and the target induced expression of a presynaptic neuropeptide critical for synapse maturation. PMID- 20573883 TI - Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels. AB - Ca(2+) influx through postsynaptic Ca(v)1.x L-type voltage-gated channels (LTCCs) is particularly effective in activating neuronal biochemical signaling pathways that might be involved in Hebbian synaptic plasticity (i.e., long-term potentiation and depression) and learning and memory. Here, we demonstrate that Ca(v)1.2 is the functionally relevant LTCC isoform in the thalamus-amygdala pathway of mice. We further show that acute pharmacological block of LTCCs abolishes Hebbian plasticity in the thalamus-amygdala pathway and impairs the acquisition of conditioned fear. On the other hand, chronic genetic loss of Ca(v)1.2 triggers a homeostatic change of the synapse, leading to a fundamental alteration of the mechanism of Hebbian plasticity by synaptic incorporation of Ca(2+)-permeable, GluA2-lacking AMPA receptors. Our results demonstrate for the first time the importance of the Ca(v)1.2 LTCC subtype in synaptic plasticity and fear memory acquisition. PMID- 20573884 TI - Taste preference for fatty acids is mediated by GPR40 and GPR120. AB - The oral perception of fat has traditionally been considered to rely mainly on texture and olfaction, but recent findings suggest that taste may also play a role in the detection of long chain fatty acids. The two G-protein coupled receptors GPR40 (Ffar1) and GPR120 are activated by medium and long chain fatty acids. Here we show that GPR120 and GPR40 are expressed in the taste buds, mainly in type II and type I cells, respectively. Compared with wild-type mice, male and female GPR120 knock-out and GPR40 knock-out mice show a diminished preference for linoleic acid and oleic acid, and diminished taste nerve responses to several fatty acids. These results show that GPR40 and GPR120 mediate the taste of fatty acids. PMID- 20573885 TI - Functional anatomical evidence for respiratory rhythmogenic function of endogenous bursters in rat medulla. AB - Endogenous burster neurons (EBs) have been found at the level of the facial nucleus (VIIn), and 500 mum caudally, within the pre-Botzinger complex (preBotC). They have been proposed as either causal to or playing no role in respiratory rhythmogenesis. Little is known about their broader distribution in ventrolateral medulla. Here, a Ca(2+) indicator was used to record respiratory network activity in ventrolateral medulla, and, following synaptic blockade, to identify EBs active at perfusate K(+) concentrations ([K(+)](o)) of 3, 6, and 9 mm. Recordings were made along the respiratory column, extending 300 mum rostrally, and 1100 mum caudally from the caudal pole of VIIn (VIIc), in the in vitro tilted sagittal slab preparation, isolated from neonate male and female Sprague Dawley rats. Activity under matching [K(+)](o) in the intact respiratory network was subsequently investigated. Respiratory neurons (n = 401) formed statistically significant clusters at the VIIc, within the preBotC, and 100 mum caudal to the preBotC. EBs (n = 693) formed statistically significant clusters that overlapped with respiratory clusters at the VIIc and preBotC. EB activity increased significantly as [K(+)](o) was increased, as did neurons that remained coupled following synaptic blockade. The overlap between respiratory and EB clusters in regions of ventrolateral medulla identified as rhythmogenic supports the hypothesis that EBs are constituents of rhythmogenic networks. In addition, the observation of truncated inspiratory bursts and ectopic bursting in respiratory neurons when [K(+)](o) was elevated in the intact network is consistent with a causal role for EBs in respiratory rhythmogenesis. PMID- 20573886 TI - Nonlinear coupling in the human motor system. AB - The synchronous discharge of neuronal assemblies is thought to facilitate communication between areas within distributed networks in the human brain. This oscillatory activity is especially interesting, given the pathological modulation of specific frequencies in diseases affecting the motor system. Many studies investigating oscillatory activity have focused on same frequency, or linear, coupling between areas of a network. In this study, our aim was to establish a functional architecture in the human motor system responsible for induced responses as measured in normal subjects with magnetoencephalography. Specifically, we looked for evidence for additional nonlinear (between-frequency) coupling among neuronal sources and, in particular, whether nonlinearities were found predominantly in connections within areas (intrinsic), between areas (extrinsic) or both. We modeled the event-related modulation of spectral responses during a simple hand-grip using dynamic casual modeling. We compared models with and without nonlinear connections under conditions of symmetric and asymmetric interhemispheric connectivity. Bayesian model comparison suggested that the task-dependent motor network was asymmetric during right hand movements. Furthermore, it revealed very strong evidence for nonlinear coupling between sources in this distributed network, but interactions among frequencies within a source appeared linear in nature. Our results provide empirical evidence for nonlinear coupling among distributed neuronal sources in the motor system and that these play an important role in modulating spectral responses under normal conditions. PMID- 20573888 TI - Wnt-5a modulates recycling of functional GABAA receptors on hippocampal neurons. AB - GABA(A) receptors (GABA(A)-Rs) play a significant role in mediating fast synaptic inhibition and it is the main inhibitory receptor in the CNS. The role of Wnt signaling in coordinating synapse structure and function in the mature CNS is poorly understood. In previous studies we found that Wnt ligands can modulate excitatory synapses through remodeling both presynaptic and postsynaptic regions. In this current study we provide evidence for the effect of Wnt-5a on postsynaptic GABA(A)-Rs. We observed that Wnt-5a induces surface expression and maintenance of this receptor in the neuronal membrane. The evoked IPSC recordings in rat hippocampal slice indicate that Wnt-5a can regulates postsynaptically the hippocampal inhibitory synapses. We found also that Wnt-5a: (a) induces the insertion and clustering of GABA(A)-Rs in the membrane; (b) increases the amplitude of GABA-currents due exclusively to postsynaptic mechanisms; (c) does not affect the endocytic process, but increases the receptor recycling. Finally, all these effects on the GABA(A)-Rs are mediated by the activation of calcium/calmodulin-dependent kinase II (CaMKII). Therefore, we postulate that Wnt 5a, by activation of CaMKII, induces the recycling of functional GABA(A)-Rs on the mature hippocampal neurons. PMID- 20573887 TI - A reward-modulated hebbian learning rule can explain experimentally observed network reorganization in a brain control task. AB - It has recently been shown in a brain-computer interface experiment that motor cortical neurons change their tuning properties selectively to compensate for errors induced by displaced decoding parameters. In particular, it was shown that the three-dimensional tuning curves of neurons whose decoding parameters were reassigned changed more than those of neurons whose decoding parameters had not been reassigned. In this article, we propose a simple learning rule that can reproduce this effect. Our learning rule uses Hebbian weight updates driven by a global reward signal and neuronal noise. In contrast to most previously proposed learning rules, this approach does not require extrinsic information to separate noise from signal. The learning rule is able to optimize the performance of a model system within biologically realistic periods of time under high noise levels. Furthermore, when the model parameters are matched to data recorded during the brain-computer interface learning experiments described above, the model produces learning effects strikingly similar to those found in the experiments. PMID- 20573889 TI - Predicting persuasion-induced behavior change from the brain. AB - Although persuasive messages often alter people's self-reported attitudes and intentions to perform behaviors, these self-reports do not necessarily predict behavior change. We demonstrate that neural responses to persuasive messages can predict variability in behavior change in the subsequent week. Specifically, an a priori region of interest (ROI) in medial prefrontal cortex (MPFC) was reliably associated with behavior change (r = 0.49, p < 0.05). Additionally, an iterative cross-validation approach using activity in this MPFC ROI predicted an average 23% of the variance in behavior change beyond the variance predicted by self reported attitudes and intentions. Thus, neural signals can predict behavioral changes that are not predicted from self-reported attitudes and intentions alone. Additionally, this is the first functional magnetic resonance imaging study to demonstrate that a neural signal can predict complex real world behavior days in advance. PMID- 20573891 TI - How does learning to read affect speech perception? AB - Behavioral studies have demonstrated that learning to read and write affects the processing of spoken language. The present study investigates the neural mechanism underlying the emergence of such orthographic effects during speech processing. Transcranial magnetic stimulation (TMS) was used to tease apart two competing hypotheses that consider this orthographic influence to be either a consequence of a change in the nature of the phonological representations during literacy acquisition or a consequence of online coactivation of the orthographic and phonological representations during speech processing. Participants performed an auditory lexical decision task in which the orthographic consistency of spoken words was manipulated and repetitive TMS was used to interfere with either phonological or orthographic processing by stimulating left supramarginal gyrus (SMG) or left ventral occipitotemporal cortex (vOTC), respectively. The advantage for consistently spelled words was removed only when the stimulation was delivered to SMG and not to vOTC, providing strong evidence that this effect arises at a phonological, rather than an orthographic, level. We propose a possible mechanistic explanation for the role of SMG in phonological processing and how this is affected by learning to read. PMID- 20573890 TI - Dopamine modulates Ih in a motor axon. AB - We studied the axons of the pyloric dilator neurons in the stomatogastric nervous system of the lobster. The several-centimeters-long portions of these axons in the motor nerves depolarize in response to low concentrations of dopamine (DA) and exhibit peripheral spike initiation in the absence of centrally generated activity. This effect is inhibited by blockers of hyperpolarization-activated inward current (I(h)). We show here that peripheral spike initiation was also elicited by D(1)-type receptor agonists and drugs that increase cAMP. This suggests that DA acts via a D(1)-type receptor mechanism to modulate hyperpolarization-activated cyclic nucleotide-gated channels. We used two electrode voltage clamp of the axon to directly study the effect of DA on I(h). Surprisingly, DA decreased the maximal conductance. However, because of a shift of the activation curve to more depolarized potentials, and a change in the slope, conductance was increased at biologically relevant membrane potentials. These changes were solely caused by modulation of I(h), as DA had no discernible effect when I(h) was blocked. In addition, they were not induced by repeated activation and could be mimicked by application of drugs that increase cAMP concentration. DA modulation of I(h) persisted in the presence of a protein kinase A inhibitor and is therefore potentially mediated by a phosphorylation independent direct effect of cAMP on the ion channel. A computer model of the axon showed that the changes in maximal conductance and voltage dependence were not qualitatively affected by space-clamp problems. PMID- 20573892 TI - Attention to memory and the environment: functional specialization and dynamic competition in human posterior parietal cortex. AB - Posterior parietal cortex has been traditionally associated with perceptual attention and sensory-motor processing, but recent studies also indicate a potential role in episodic memory retrieval. Here, we developed a new paradigm to isolate top-down attention-related activity directed to either memory or perceptual information. We demonstrated a robust topographic separation in human posterior parietal cortex associated with searching for task-relevant information in episodic memory or in the environment. Control analyses confirmed that this difference was not dependent on differences in sensory stimulation or eye movements across tasks. Notably, we observed in memory- and perception-related regions a mechanism of reciprocal dynamic competition that was related to behavioral performance. These results provide the first evidence for a double dissociation between parietal networks involved in top-down attention to memory and the environment and support the idea of neural competition between perception and memory. PMID- 20573893 TI - Cdk5-mediated phosphorylation of delta-catenin regulates its localization and GluR2-mediated synaptic activity. AB - Cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation plays an important role in proper synaptic function and transmission. Loss of Cdk5 activity results in abnormal development of the nervous system accompanied by massive disruptions in cortical migration and lamination, therefore impacting synaptic activity. The Cdk5 activator p35 associates with delta-catenin, the synaptic adherens junction protein that serves as part of the anchorage complex of AMPA receptor at the postsynaptic membrane. However, the implications of Cdk5-mediated phosphorylation of delta-catenin have not been fully elucidated. Here we show that Cdk5-mediated phosphorylation of delta-catenin regulates its subcellular localization accompanied by changes in dendritic morphogenesis and synaptic activity. We identified two Cdk5 phosphorylation sites in mouse delta-catenin, serines 300 and 357, and report that loss of Cdk5 phosphorylation of delta-catenin increased its localization to the membrane. Furthermore, mutations of the serines 300 and 357 to alanines to mimic nonphosphorylated delta-catenin resulted in increased dendritic protrusions accompanied by increased AMPA receptor subunit GluR2 localization at the membrane. Consistent with these observations, loss of Cdk5 phosphorylation of delta-catenin increased the AMPA/NMDA ratio. This study reveals how Cdk5 phosphorylation of the synaptic mediator protein delta-catenin can alter its localization at the synapse to impact neuronal synaptic activity. PMID- 20573894 TI - Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation. AB - Brain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been shown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A(2A) receptor activation, we hypothesized that activation of A(2A) receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A(2A) receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansylcadaverine (100 microm) did not modify the effects of the A(2A) receptor agonists but significantly impaired BDNF effects on TrkB recruitment to lipid rafts. The effect of A(2A) receptor activation in TrkB localization was mimicked by 5 microm forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14-22), and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF on hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts induced by activation of adenosine A(2A) receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity. PMID- 20573895 TI - Social cognitive conflict resolution: contributions of domain-general and domain specific neural systems. AB - Cognitive control mechanisms allow individuals to behave adaptively in the face of complex and sometimes conflicting information. Although the neural bases of these control mechanisms have been examined in many contexts, almost no attention has been paid to their role in resolving conflicts between competing social cues, which is surprising given that cognitive conflicts are part of many social interactions. Evidence about the neural processing of social information suggests that two systems--the mirror neuron system (MNS) and mental state attribution system (MSAS)--are specialized for processing nonverbal and contextual social cues, respectively. This could support a model of social cognitive conflict resolution in which competition between social cues would recruit domain-general cognitive control mechanisms, which in turn would bias processing toward the MNS or MSAS. Such biasing could also alter social behaviors, such as inferences made about the internal states of others. We tested this model by scanning participants using functional magnetic resonance imaging while they drew inferences about the social targets' emotional states based on congruent or incongruent nonverbal and contextual social cues. Conflicts between social cues recruited the anterior cingulate and lateral prefrontal cortex, brain areas associated with domain-general control processes. This activation was accompanied by biasing of neural activity toward areas in the MNS or MSAS, which tracked, respectively, with perceivers' behavioral reliance on nonverbal or contextual cues when drawing inferences about targets' emotions. Together, these data provide evidence about both domain-general and domain-specific mechanisms involved in resolving social cognitive conflicts. PMID- 20573896 TI - Efficacy loss of the anticonvulsant carbamazepine in mice lacking sodium channel beta subunits via paradoxical effects on persistent sodium currents. AB - Neuronal excitability is critically determined by the properties of voltage-gated Na(+) currents. Fast transient Na(+) currents (I(NaT)) mediate the fast upstroke of action potentials, whereas low-voltage-activated persistent Na(+) currents (I(NaP)) contribute to subthreshold excitation. Na(+) channels are composed of a pore-forming alpha subunit and beta subunits, which modify the biophysical properties of alpha subunits. We have examined the idea that the presence of beta subunits also modifies the pharmacological properties of the Na(+) channel complex using mice lacking either the beta(1) (Scn1b) or beta(2) (Scn2b) subunit. Classical effects of the anticonvulsant carbamazepine (CBZ), such as the use dependent reduction of I(NaT) and effects on I(NaT) voltage dependence of inactivation, were unaltered in mice lacking beta subunits. Surprisingly, CBZ induced a small but significant shift of the voltage dependence of activation of I(NaT) and I(NaP) to more hyperpolarized potentials. This novel CBZ effect on I(NaP) was strongly enhanced in Scn1b null mice, leading to a pronounced increase of I(NaP) within the subthreshold potential range, in particular at low CBZ concentrations of 10-30 microm. A combination of current-clamp and computational modeling studies revealed that this effect causes a complete loss of CBZ efficacy in reducing repetitive firing. Thus, beta subunits modify not only the biophysical but also the pharmacological properties of Na(+) channels, in particular with respect to I(NaP). Consequently, altered expression of beta subunits in other neurological disorders may cause altered neuronal sensitivity to drugs targeting Na(+) channels. PMID- 20573897 TI - Neural correlates of active avoidance behavior in superior colliculus. AB - Active avoidance of harmful situations seems highly adaptive, but the underlying neural mechanisms are unknown. Rats can effectively use the superior colliculus during active avoidance to detect a salient whisker conditioned stimulus (WCS) that signals an aversive event. Here, we recorded unit and field potential activity in the intermediate layers of the superior colliculus of rats during active avoidance behavior. During the period preceding the onset of the WCS, avoids are associated with a higher firing rate than escapes (unsuccessful avoids), indicating that a prepared superior colliculus is more likely to detect the WCS and lead to an avoid. Moreover, during the WCS, a robust ramping up of the overall firing rate is observed for trials leading to avoids. The firing rate ramping is not caused by shuttling and may serve to drive downstream circuits to avoid. Therefore, a robust neural correlate of active avoidance behavior is found in the superior colliculus, emphasizing its role in the detection of salient sensory signals that require immediate action. PMID- 20573898 TI - Inhibitory motor control in response stopping and response switching. AB - While much is known about the neural regions recruited in the human brain when a dominant motor response becomes inappropriate and must be stopped, less is known about the regions that support switching to a new, appropriate, response. Using functional magnetic resonance imaging with two variants of the stop-signal paradigm that require either stopping altogether or switching to a different response, we examined the brain systems involved in these two forms of executive control. Both stopping trials and switching trials showed common recruitment of the right inferior frontal gyrus, presupplementary motor area, and midbrain. Contrasting switching trials with stopping trials showed activation similar to that observed on response trials (where the initial response remains appropriate and no control is invoked), whereas there were no regions that showed significantly greater activity for stopping trials compared with switching trials. These results show that response switching can be supported by the same neural systems as response inhibition, and suggest that the same mechanism of rapid, nonselective response inhibition that is thought to support speeded response stopping can also support speeded response switching when paired with execution of the new, appropriate, response. PMID- 20573899 TI - Prefrontal cortex activity during flexible categorization. AB - Items are categorized differently depending on the behavioral context. For instance, a lion can be categorized as an African animal or a type of cat. We recorded lateral prefrontal cortex (PFC) neural activity while monkeys switched between categorizing the same image set along two different category schemes with orthogonal boundaries. We found that each category scheme was largely represented by independent PFC neuronal populations and that activity reflecting a category distinction was weaker, but not absent, when that category was irrelevant. We suggest that the PFC represents competing category representations independently to reduce interference between them. PMID- 20573900 TI - Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during glial-guided neuronal migration. AB - Glial-guided neuronal migration is a key step in the development of laminar architecture of cortical regions of the mammalian brain. We previously reported that neuronal protein astrotactin (ASTN1) functions as a neuron-glial ligand during CNS glial-guided migration. Here, we identify a new Astn family member, Astn2, that is expressed at high levels in migrating, cerebellar granule neurons, along with Astn1, at developmental stages when glial-guided migration is ongoing. Biochemical and flow cytometry experiments show that ASTN2 forms a complex with ASTN1 and regulates surface expression of ASTN1. Live imaging of Venus-tagged ASTN1 in migrating cerebellar granule cells reveals the intracellular trafficking of ASTN1-Venus, with ASTN1-Venus accumulating in the forward aspect of the leading process where new sites of adhesion will form. Treatment of migrating neurons with Dynasore, a soluble noncompetitive inhibitor of Dynamin, rapidly arrests the migration of immature granule cells in a reversible manner, suggesting the critical importance of receptor trafficking to neuronal locomotion along Bergmann glial fibers in the developing cerebellum. Together, these findings suggest that ASTN2 regulates the levels of ASTN1 in the plasma membrane and that the release of neuronal adhesions to the glial fiber during neuronal locomotion involves the intracellular trafficking of ASTN1. PMID- 20573901 TI - Neural mechanisms underlying the impact of visual distraction on retrieval of long-term memory. AB - Filtering information on the basis of what is relevant to accomplish our goals is a critical process supporting optimal cognitive performance. However, it is not known whether exposure to irrelevant environmental stimuli impairs our ability to accurately retrieve long-term memories. We hypothesized that visual processing of irrelevant visual information would interfere with mental visualization engaged during recall of the details of a prior experience, despite goals to direct full attention to the retrieval task. In the current study, we compared performance on a cued-recall test of previously studied visual items when participants' eyes were closed to performance when their eyes were open and irrelevant visual stimuli were presented. A behavioral experiment revealed that recollection of episodic details was diminished in the presence of the irrelevant information. A functional magnetic resonance imaging experiment using the same paradigm replicated the behavioral results and found that diminished recollection was associated with the disruption of functional connectivity in a network involving the left inferior frontal gyrus, hippocampus and visual association cortex. Network connectivity supported recollection of contextual details based on visual imagery when eyes were closed, but declined in the presence of irrelevant visual information. We conclude that bottom-up influences from irrelevant visual information interfere with top-down selection of episodic details mediated by a capacity-limited frontal control region, resulting in impaired recollection. PMID- 20573902 TI - Dipeptidyl peptidase-like protein 6 is required for normal electrophysiological properties of cerebellar granule cells. AB - In cerebellar granule (CG) cells and many other neurons, A-type potassium currents play an important role in regulating neuronal excitability, firing patterns, and activity-dependent plasticity. Protein biochemistry has identified dipeptidyl peptidase-like protein 6 (DPP6) as an auxiliary subunit of Kv4-based A type channels and thus a potentially important regulator of neuronal excitability. In this study, we used an RNA interference (RNAi) strategy to examine the role DPP6 plays in forming and shaping the electrophysiological properties of CG cells. DPP6 RNAi delivered by lentiviral vectors effectively disrupts DPP6 protein expression in CG cells. In response to the loss of DPP6, I(SA) peak conductance amplitude is reduced by >85% in parallel with a dramatic reduction in the level of I(SA) channel protein complex found in CG cells. The I(SA) channels remaining in CG cells after suppression of DPP6 show alterations in gating similar to Kv4 channels expressed in heterologous systems without DPP6. In addition to these effects on A-type current, we find that loss of DPP6 has additional effects on input resistance and Na(+) channel conductance that combine with the effects on I(SA) to produce a global change in excitability. Overall, DPP6 expression seems to be critical for the expression of a high-frequency electrophysiological phenotype in CG cells by increasing leak conductance, A-type current levels and kinetics, and Na(+) current amplitude. PMID- 20573904 TI - Kisspeptin signaling is required for peripheral but not central stimulation of gonadotropin-releasing hormone neurons by NMDA. AB - NMDA and kisspeptins can stimulate gonadotropin-releasing hormone (GnRH) release after peripheral or central administration in mice. To determine whether these agonists act independently or through a common pathway, we have examined their ability to stimulate GnRH/luteinizing hormone (LH) release after peripheral or central administration in Kiss1- or Gpr54 (Kiss1r)-null mutant mice. Peripheral injection of NMDA failed to stimulate GnRH/LH release in prepubertal or gonadally intact mutant male mice. Dual-labeling experiments indicated a direct activation of Kiss1-expressing neurons in the arcuate nucleus. In contrast, central injection of NMDA into the lateral ventricle increased plasma LH levels in both Kiss1 and Gpr54 mutant male mice similar to the responses in wild-type mice. Central injection of NMDA stimulated c-Fos expression throughout the hypothalamus but not in GnRH neurons, suggesting an action at the nerve terminals only. In contrast, kisspeptin-10 stimulated LH release after both central and peripheral injection but induced c-Fos expression in GnRH neurons only after central administration. Finally, central injection of NMDA induces c-Fos expression in catecholamine- and nitric oxide-producing neurons in the hypothalamus of mutant mice, indicating a possible kisspeptin-independent GnRH/LH release by NMDA through activation of these neurons. Thus, NMDA may act at both GnRH cell bodies (kisspeptin-independent) and nerve terminals (kisspeptin-dependent) in a dual way to participate in the GnRH/LH secretion in the male mouse. PMID- 20573903 TI - Role of presenilins in neuronal calcium homeostasis. AB - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca(2+)) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca(2+) leak channels. To directly investigate the role of presenilins in neuronal ER Ca(2+) homeostasis, we here performed a series of Ca(2+) imaging experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L)). Obtained results provided additional support to the hypothesis that presenilins function as ER Ca(2+) leak channels in neurons. Interestingly, we discovered that presenilins play a major role in ER Ca(2+) leak function in hippocampal but not in striatal neurons. We further discovered that, in hippocampal neurons, loss of presenilin-mediated ER Ca(2+) leak function was compensated by an increase in expression and function of ryanodine receptors (RyanRs). Long-term feeding of the RyanR inhibitor dantrolene to amyloid precursor protein-presenilin-1 mice (Thy1-APP(KM670/671NL), Thy1 PS1(L166P)) resulted in an increased amyloid load, loss of synaptic markers, and neuronal atrophy in hippocampal and cortical regions. These results indicate that disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesis. PMID- 20573905 TI - Ventromedial and orbital prefrontal neurons differentially encode internally and externally driven motivational values in monkeys. AB - The value of events that predict future rewards, thereby driving behavior, is sensitive to information arising from external (environmental) and internal factors. The ventral prefrontal cortex, an anatomically heterogeneous area, has information related to this value. We designed experiments to compare the contribution of two distinct subregions, orbital and ventromedial, of the ventral prefrontal cortex to the encoding of internal and external factors controlling the perceived motivational value. We recorded the activity of single neurons in both regions in monkeys while manipulating internal and external factors that should affect the perceived value of task events. Neurons in both regions encoded the value of task events, with orbitofrontal neurons being more sensitive to external factors such as visual cues and ventromedial neurons being more sensitive to internal factors such as satiety. Thus, the orbitofrontal cortex emphasizes signals for evaluating environment-centered, externally driven motivational processes, whereas ventromedial prefrontal cortex emphasizes signals more suited for subject-centered, internally driven motivational processes. PMID- 20573906 TI - Disease-modifying effects of phenobarbital and the NKCC1 inhibitor bumetanide in the pilocarpine model of temporal lobe epilepsy. AB - Accumulating evidence suggests that changes in neuronal chloride homeostasis may be involved in the mechanisms by which brain insults induce the development of epilepsy. A variety of brain insults, including status epilepticus (SE), lead to changes in the expression of the cation-chloride cotransporters KCC2 and NKCC1, resulting in intracellular chloride accumulation and reappearance of immature, depolarizing synaptic responses to GABA(A) receptor activation, which may critically contribute to the neuronal hyperexcitability underlying epileptogenesis. In the present study, it was evaluated whether prolonged administration of the selective NKCC1 inhibitor, bumetanide, after a pilocarpine induced SE modifies the development of epilepsy in adult female rats. The antiepileptic drug phenobarbital, either alone or in combination, was used for comparison. Based on pharmacokinetic studies with bumetanide, which showed extremely rapid elimination and low brain penetration of this drug in rats, bumetanide was administered systemically with different dosing protocols, including continuous intravenous infusion. As shown by immunohistochemistry, neuronal NKCC1 expression was markedly upregulated shortly after SE. Prophylactic treatment with phenobarbital after SE reduced the number of rats developing spontaneous seizures and decreased seizure frequency, indicating a disease modifying effect. Bumetanide did not exert any significant effects on development of spontaneous seizures nor did it enhance the effects of phenobarbital. However, combined treatment with both drugs counteracted several of the behavioral consequences of SE, which was not observed with single drug treatment. These data do not indicate that bumetanide can prevent epilepsy after SE, but the disease modifying effect of this drug warrants further studies with more lipophilic prodrugs of bumetanide. PMID- 20573907 TI - Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy. AB - Adult neurogenesis remains controversial in the cerebral cortex. We have previously shown in monkeys and rats that reactive neurogenesis occurs in the spinal dorsal horn 6-8 weeks after a cervical dorsal rhizotomy. Here, in three monkeys with the same lesion, we asked whether it also occurs coincidentally in the corresponding primary somatosensory and motor cortex, where significant topographic and neuronal reorganization is known to occur. Monkeys (male Macaca fascicularis) were given 5-bromo-2-deoxyuridine (BrdU) injections 2-3 weeks after the rhizotomy, and were perfused 4-6 weeks later. Cells colabeled for BrdU and five different neuronal markers were observed within the primary somatosensory and motor cortex, and their distributions were compared bilaterally. Cells colabeled with BrdU and the astrocytic marker glial fibrillary acidic protein (GFAP) were also quantified for comparison. A significant number of BrdU/NeuN- and BrdU/calbindin-colabeled cells were observed in topographically reorganized cortex. Small numbers of BrdU/GFAP-colabeled cells were also consistently observed bilaterally, but these cells were never colabeled with any of the neuronal markers. Of the cells colabeled with BrdU and a neuronal marker, at least half had an inhibitory phenotype. However, excitatory pyramidal neurons were also identified with classic pyramidal morphology. Cortical neurogenesis was not observed in other cortical regions. It was also not observed in the primary sensorimotor, prefrontal, or posterior parietal cortex in an additional control monkey (male Macaca fascicularis) that had no surgical intervention. Our findings provide evidence for reactive endogenous cortical neurogenesis after a dorsal rhizotomy, which may play a role in functional recovery. PMID- 20573908 TI - Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. AB - Recent studies indicate that persistent pain after tissue or nerve injury is accompanied by an enhanced net descending facilitatory drive that contributes to an amplification and spread of pain. Although 5-HT-containing neurons in the rostral ventromedial medulla (RVM) provide the major descending serotonergic projection to the spinal cord, it is not clear whether the neurotransmitter 5-HT itself released from RVM-spinal neurons contributes to descending pain modulation. In the present study, we determined the role of the descending 5-HT in rat nocifensive behaviors after persistent pain by selectively depleting functional phenotypes of 5-HT in RVM neurons with regional shRNA interference (RNAi) of tryptophan hydroxylase-2 (Tph-2), the rate-limiting enzyme in the synthesis of neuronal 5-HT. Compared to negative control shRNA, Tph-2 shRNA induced significantly prolonged downregulation of Tph-2 in the RVM and 5-HT in spinal dorsal horn. The 5-HT-depleted rats showed normal pain sensitivity in responses to acute noxious stimulation. However, the same RNAi treatment attenuated formalin-induced spontaneous nocifensive responses and tissue or nerve injury-induced allodynia and hyperalgesia. Furthermore, in control shRNA-treated animals, intra-RVM microinjection of brain-derived neurotrophic factor produced a reversible hyperalgesia, which was completely prevented by Tph-2 RNAi pretreatment. Descending inhibition induced by intra-RVM electrical stimulation, but not microinjection of the mu- or kappa-opioid receptor agonists in control shRNA-treated animals was eliminated in 5-HT-depleted rats. These results indicate that the descending 5-HT from the RVM is an important contributor to pain facilitation during the development of persistent pain, and may not mediate opioid-induced descending inhibition in acute pain. PMID- 20573909 TI - Coregulation of ion channel conductances preserves output in a computational model of a crustacean cardiac motor neuron. AB - Similar activity patterns at both neuron and network levels can arise from different combinations of membrane and synaptic conductance values. A strategy by which neurons may preserve their electrical output is via cell type-dependent balances of inward and outward currents. Measurements of mRNA transcripts that encode ion channel proteins within motor neurons in the crustacean cardiac ganglion recently revealed correlations between certain channel types. To determine whether balances of intrinsic currents potentially resulting from such correlations preserve certain electrical cell outputs, we developed a nominal biophysical model of the crustacean cardiac ganglion using biological data. Predictions from the nominal model showed that coregulation of ionic currents may preserve the key characteristics of motor neuron activity. We then developed a methodology of sampling a multidimensional parameter space to select an appropriate model set for meaningful comparison with variations in correlations seen in biological datasets. PMID- 20573911 TI - Actomyosin contraction at the cell rear drives nuclear translocation in migrating cortical interneurons. AB - Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement. The participation of actomyosin driven forces acting at the nucleus rear has been suggested, however its precise contribution has not been directly addressed. By analyzing interneurons migrating in cortical slices of mouse brains, we have found that nucleokinesis is associated with a precise pattern of actin dynamics characterized by the initial formation of a cup-like actin structure at the rear nuclear pole. Time-lapse experiments show that progressive actomyosin contraction drives the nucleus forward. Nucleokinesis concludes with the complete contraction of the cup-like structure, resulting in an actin spot at the base of the retracting trailing process. Our results demonstrate that this actin remodeling requires a threshold calcium level provided by low-frequency spontaneous fast intracellular calcium transients. Microtubule stabilization with taxol treatment prevents actin remodeling and nucleokinesis, whereas cells with a collapsed microtubule cytoskeleton induced by nocodazole treatment, display nearly normal actin dynamics and nucleokinesis. In summary, the results presented here demonstrate that actomyosin forces acting at the rear side of the nucleus drives nucleokinesis in tangentially migrating interneurons in a process that requires calcium and a dynamic cytoskeleton of microtubules. PMID- 20573910 TI - Pulvinar inactivation disrupts selection of movement plans. AB - The coordinated movement of the eyes and hands under visual guidance is an essential part of goal-directed behavior. Several cortical areas known to be involved in this process exchange projections with the dorsal aspect of the thalamic pulvinar nucleus, suggesting that this structure may play a central role in visuomotor behavior. Here, we used reversible inactivation to investigate the role of the dorsal pulvinar in the selection and execution of visually guided manual and saccadic eye movements in macaque monkeys. We found that unilateral pulvinar inactivation resulted in a spatial neglect syndrome accompanied by visuomotor deficits including optic ataxia during visually guided limb movements. Monkeys were severely disrupted in their visually guided behavior regarding space contralateral to the side of the injection in several domains, including the following: (1) target selection in both manual and oculomotor tasks, (2) limb usage in a manual retrieval task, and (3) spontaneous visual exploration. In addition, saccades into the ipsilesional field had abnormally short latencies and tended to overshoot their mark. None of the deficits could be explained by a visual field defect or primary motor deficit. These findings highlight the importance of the dorsal aspect of the pulvinar nucleus as a critical hub for spatial attention and selection of visually guided actions. PMID- 20573912 TI - Direct evidence for wake-related increases and sleep-related decreases in synaptic strength in rodent cortex. AB - Despite evidence that waking is associated with net synaptic potentiation and sleep with depression, direct proof for changes in synaptic currents is lacking in large brain areas such as the cerebral cortex. By recording miniature EPSCs (mEPSCs) from frontal cortex slices of mice and rats that had been awake or asleep, we found that the frequency and amplitude of mEPSCs increased after waking and decreased after sleep, independent of time of day. Recovery sleep after deprivation also decreased mEPSCs, suggesting that sleep favors synaptic homeostasis. Since stronger synapses require more energy, space, and supplies, a generalized renormalization of synapses may be an important function of sleep. PMID- 20573914 TI - On the role of prestimulus alpha rhythms over occipito-parietal areas in visual input regulation: correlation or causation? AB - The posterior alpha rhythm (8-14 Hz), originating in occipito-parietal areas through thalamocortical generation, displays characteristics of visual activity in anticipation of visual events. Posterior alpha power is influenced by visual spatial attention via top-down control from higher order attention areas such as the frontal eye field. It covaries with visual cortex excitability, as tested through transcranial magnetic stimulation (TMS), and predicts the perceptual fate of a forthcoming visual stimulus. Yet, it is still unknown whether the nature of the relationship between this prestimulus alpha oscillation and upcoming perception is causal or only correlative. Here, we tested in the human brain whether the oscillation in the alpha band is causally shaping perception through directly stimulating visual areas via short trains of rhythmic TMS. We compared stimulation at alpha frequency (10 Hz) with two control frequencies in the theta (5 Hz) and beta bands (20 Hz), and assessed immediate perceptual outcomes. Target visibility was significantly modulated by alpha stimulation, relative to both control conditions. Alpha stimulation selectively impaired visual detection in the visual field opposite to the stimulated hemisphere, while enhancing detection ipsilaterally. These frequency-specific effects were observed both for stimulation over occipital and parietal areas of the left and right hemispheres and were short lived: they were observed by the end of the TMS train but were absent 3 s later. This shows that the posterior alpha rhythm is actively involved in shaping forthcoming perception and, hence, constitutes a substrate rather than a mere correlate of visual input regulation. PMID- 20573913 TI - A novel population of myeloid cells responding to coxsackievirus infection assists in the dissemination of virus within the neonatal CNS. AB - Enterovirus infection in newborn infants is a significant cause of aseptic meningitis and encephalitis. Using a neonatal mouse model, we previously determined that coxsackievirus B3 (CVB3) preferentially targets proliferating neural stem cells located in the subventricular zone within 24 h after infection. At later time points, immature neuroblasts, and eventually mature neurons, were infected as determined by expression of high levels of viral protein. Here, we show that blood-derived Mac3(+) mononuclear cells were rapidly recruited to the CNS within 12 h after intracranial infection with CVB3. These cells displayed a myeloid-like morphology, were of a peripheral origin based on green fluorescent protein (GFP)-tagged adoptive cell transplant examination, and were highly susceptible to CVB3 infection during their migration into the CNS. Serial immunofluorescence images suggested that the myeloid cells enter the CNS via the choroid plexus, and that they may be infected during their extravasation and passage through the choroid plexus epithelium; these infected myeloid cells ultimately penetrate into the parenchyma of the brain. Before their migration through the ependymal cell layer, a subset of these infected myeloid cells expressed detectable levels of nestin, a marker for neural stem and progenitor cells. As these nestin(+) myeloid cells infected with CVB3 migrated through the ependymal cell layer, they revealed distinct morphological characteristics typical of type B neural stem cells. The recruitment of these novel myeloid cells may be specifically set in motion by the induction of a unique chemokine profile in the CNS induced very early after CVB3 infection, which includes upregulation of CCL12. We propose that intracranial CVB3 infection may lead to the recruitment of nestin(+) myeloid cells into the CNS which might represent an intrinsic host CNS repair response. In turn, the proliferative and metabolic status of recruited myeloid cells may render them attractive targets for CVB3 infection. Moreover, the migratory ability of these myeloid cells may point to a productive method of virus dissemination within the CNS. PMID- 20573915 TI - Accountability measures--using measurement to promote quality improvement. PMID- 20573916 TI - Limbal stem-cell therapy and long-term corneal regeneration. AB - BACKGROUND: Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease. METHODS: We used autologous limbal stem cells cultivated on fibrin to treat 112 patients with corneal damage, most of whom had burn-dependent limbal stem-cell deficiency. Clinical results were assessed by means of Kaplan Meier, Kruskal-Wallis, and univariate and multivariate logistic-regression analyses. We also assessed the clinical outcome according to the percentage of holoclone-forming stem cells, detected as cells that stain intensely (p63-bright cells) in the cultures. RESULTS: Permanent restoration of a transparent, renewing corneal epithelium was attained in 76.6% of eyes. The failures occurred within the first year. Restored eyes remained stable over time, with up to 10 years of follow-up (mean, 2.91+/-1.99; median, 1.93). In post hoc analyses, success--that is, the generation of normal epithelium on donor stroma--was associated with the percentage of p63-bright holoclone-forming stem cells in culture. Cultures in which p63-bright cells constituted more than 3% of the total number of clonogenic cells were associated with successful transplantation in 78% of patients. In contrast, cultures in which such cells made up 3% or less of the total number of cells were associated with successful transplantation in only 11% of patients. Graft failure was also associated with the type of initial ocular damage and postoperative complications. CONCLUSIONS: Cultures of limbal stem cells represent a source of cells for transplantation in the treatment of destruction of the human cornea due to burns. PMID- 20573917 TI - The new recommendations on duty hours from the ACGME Task Force. PMID- 20573918 TI - Buying health care, the individual mandate, and the Constitution. PMID- 20573920 TI - The uncritical use of high-tech medical imaging. PMID- 20573919 TI - Is computed tomography safe? PMID- 20573921 TI - Images in clinical medicine. Benign paroxysmal positional vertigo. PMID- 20573922 TI - The bumpy road to polio eradication. PMID- 20573923 TI - Fractional doses of inactivated poliovirus vaccine in Oman. AB - BACKGROUND: We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries. METHODS: We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose. RESULTS: A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P=0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups. CONCLUSIONS: These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767.) PMID- 20573924 TI - Implications of a circulating vaccine-derived poliovirus in Nigeria. AB - BACKGROUND: The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV). METHODS: We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared. RESULTS: No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV. CONCLUSIONS: The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge. PMID- 20573925 TI - Early use of TIPS in patients with cirrhosis and variceal bleeding. AB - BACKGROUND: Patients with cirrhosis in Child-Pugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic portosystemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. METHODS: We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapy-EBL group, 31 patients). RESULTS: During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapy-EBL group as compared with 1 patient in the early TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapy-EBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapy-EBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapy-EBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapy-EBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapy-EBL group than in the early-TIPS group. No significant differences were observed between the two treatment groups with respect to serious adverse events. CONCLUSIONS: In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with significant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.) PMID- 20573926 TI - Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. AB - BACKGROUND: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy. METHODS: We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects. RESULTS: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease. CONCLUSIONS: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.) PMID- 20573927 TI - Clinical practice. Endometriosis. PMID- 20573928 TI - Genetic disorders of renal phosphate transport. PMID- 20573929 TI - Images in clinical medicine. Radiologic signs of pneumoperitoneum. PMID- 20573930 TI - Case records of the Massachusetts General Hospital. Case 19-2010. A 35-year-old man with adenocarcinoma of the cecum. PMID- 20573931 TI - Early TIPS to improve survival in acute variceal bleeding. PMID- 20573932 TI - Rifaximin treatment in hepatic encephalopathy. PMID- 20573933 TI - Prevalence of diabetes among men and women in China. PMID- 20573934 TI - Ivermectin versus malathion for head lice. PMID- 20573935 TI - Newborn-care training in developing countries. PMID- 20573936 TI - The ABIM and recertification. PMID- 20573937 TI - Mixed lymphohematopoietic chimerism and response in Wegener's granulomatosis. PMID- 20573938 TI - Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study. AB - OBJECTIVE: Prospective studies show that high C-reactive protein (CRP) levels predict diabetes and cardiovascular disease (CVD), but changes in this marker preceding disease onset are not well characterized. This study describes CRP trajectories prior to type 2 diabetes onset and fatal CVD. METHODS: In a prospective cohort of 7350 British civil servants (70% male, mean age 51 years), 558 incident type 2 diabetes cases (75-g oral glucose tolerance test, doctor's diagnosis, or self-report) and 125 certified fatal cardiovascular events were observed during a median follow-up of >14 years. Trajectories of logarithmically transformed CRP levels prior to incident diabetes or fatal cardiovascular event (cases), or the end of follow-up (controls) were calculated using multilevel modeling. RESULTS: Baseline CRP levels were higher among participants who developed diabetes (median (interquartile range) 1.44 (2.39) vs 0.78 (1.21) mg/l) or fatal CVD (1.49 (2.47) vs 0.84 (1.30) mg/l) compared with controls (both P<0.0001). In models adjusted for age, sex, body mass index, ethnicity, and employment grade, CRP levels increased with time among both incident diabetes cases and controls (P<0.0001), but this increase was less steep for cases group (P<0.05). CRP levels followed increasing linear trajectories in fatal cardiovascular cases and controls (P<0.0001) with no slope difference between the groups. CONCLUSIONS: CRP levels were higher among those who subsequently developed diabetes or died from CVD. For type 2 diabetes, age-related increase in CRP levels was less steep in the cases group than in controls, whereas for fatal CVD these trajectories were parallel. PMID- 20573939 TI - Validation of cross-sectional time series and multivariate adaptive regression splines models for the prediction of energy expenditure in children and adolescents using doubly labeled water. AB - Accurate, nonintrusive, and inexpensive techniques are needed to measure energy expenditure (EE) in free-living populations. Our primary aim in this study was to validate cross-sectional time series (CSTS) and multivariate adaptive regression splines (MARS) models based on observable participant characteristics, heart rate (HR), and accelerometer counts (AC) for prediction of minute-by-minute EE, and hence 24-h total EE (TEE), against a 7-d doubly labeled water (DLW) method in children and adolescents. Our secondary aim was to demonstrate the utility of CSTS and MARS to predict awake EE, sleep EE, and activity EE (AEE) from 7-d HR and AC records, because these shorter periods are not verifiable by DLW, which provides an estimate of the individual's mean TEE over a 7-d interval. CSTS and MARS models were validated in 60 normal-weight and overweight participants (ages 5-18 y). The Actiheart monitor was used to simultaneously measure HR and AC. For prediction of TEE, mean absolute errors were 10.7 +/- 307 kcal/d and 18.7 +/- 252 kcal/d for CSTS and MARS models, respectively, relative to DLW. Corresponding root mean square error values were 305 and 251 kcal/d for CSTS and MARS models, respectively. Bland-Altman plots indicated that the predicted values were in good agreement with the DLW-derived TEE values. Validation of CSTS and MARS models based on participant characteristics, HR monitoring, and accelerometry for the prediction of minute-by-minute EE, and hence 24-h TEE, against the DLW method indicated no systematic bias and acceptable limits of agreement for pediatric groups and individuals under free-living conditions. PMID- 20573940 TI - A population's distribution of Healthy Eating Index-2005 component scores can be estimated when more than one 24-hour recall is available. AB - The USDA's Healthy Eating Index-2005 (HEI-2005) is a tool to quantify the quality of diet consumed by individuals in the U.S. It comprises 12 components expressed as ratios of a food group or nutrient intake to energy intake. Components are scored on a scale from 0 to M, where M is 5, 10, or 20. Ideally, the HEI-2005 is calculated on the basis of the usual, or long-term average, dietary intake of an individual. In recent cycles of the NHANES, intake data have been collected via 24-h recalls for more than 1 d on most participants. We present here a statistical method to estimate a population's distribution of usual HEI-2005 component scores when >or=2 d of dietary information is available for a sample of individuals from the population. Distributions for the total population and for age-gender subgroups may be estimated. The method also yields an estimate of the population's mean total HEI-2005 score. Application of the method to NHANES data for 2001-2004 yielded estimated distributions for all 12 components; those of total vegetables (range 0-5), whole grains (range 0-5), and energy from solid fats, alcoholic beverages, and added sugars (range 0-20) are presented. The total population mean scores for these components were 3.21, 1.00, and 8.41, respectively. An estimated 30% of the total population had a score of <2.5 for total vegetables. This is the first time, to our knowledge, that estimated distributions of usual HEI-2005 component scores have been published. PMID- 20573941 TI - Heat treatment of expressed breast milk is a feasible option for feeding HIV exposed, uninfected children after 6 months of age in rural Zimbabwe. AB - In the context of a prevention of mother to child transmission of HIV program promoting exclusive breast-feeding (EBF) to 6 mo and offering HIV-PCR testing at approximately 6 mo, we ascertained the feasibility of expressing and heat treating (EHT) all breast milk fed to HIV-exposed, uninfected infants following 6 mo of EBF. Twenty mother-baby pairs were enrolled from a hospital in rural Zimbabwe. Research nurses provided lactation, EHT, and complementary feeding counseling through 21 home visits conducted over an 8-wk period and collected quantitative and qualitative data on the mothers' EHT experiences, children's diets, and anthropometric measurements. Mothers kept daily logs of EHT volumes and direct breast-feeding episodes. Mothers successfully initiated and sustained EHT for 4.5 mo (range, 1-11 mo), feeding 426 +/- 227 mL/d (mean +/- SD). By wk 2 of follow-up, children were receiving EHT and Nutributter-enriched complementary foods that satisfied 100% of their energy requirements. During the 8-wk follow-up period, no growth faltering was experienced [changes in weight-for-age, weight for-length, and length-for-age Z scores = +0.03 +/- 0.50; +0.77 +/- 1.59; and +0.02 +/- 0.85 (mean +/- SD), respectively]. Stigma was not a major deterrent, likely due to a social marketing campaign for EBF that promoted EHT as a practice to sustain breast-feeding for all women. This study provides evidence that resource-poor rural women can initiate and sustain EHT given family and health systems support. EHT provides a strategy for improving the diets of HIV-exposed but uninfected children after direct breast-feeding has ceased. PMID- 20573942 TI - Serum homocysteine and folate concentrations are associated with prevalent age related hearing loss. AB - Elevated total serum homocysteine (tHcy) concentrations associated with vitamin B 12 or folate deficiencies may adversely affect blood flow to the cochlea, leading to age-related hearing loss (presbycusis). However, only 2 small cross-sectional studies have assessed the link between folate, vitamin B-12, or tHcy and presbycusis. We aimed to determine both the cross-sectional and longitudinal association between serum concentrations of folate, vitamin B-12, or tHcy and risk of age-related hearing loss. The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss (1997-1999 to 2002-2004). Presbycusis was measured in 2956 participants (aged >or=50 y) and was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz >25 dB hearing level (HL). Serum concentrations of folate, vitamin B-12, and tHcy were determined from blood samples. Participants with elevated tHcy (>20 micromol/L) concentrations had a 64% increased likelihood of prevalent hearing loss (>25 dB HL) [multivariate-adjusted odds ratio (OR) 1.64; 95% CI, 1.06-2.53]. Low serum folate levels (<11 nmol/L) increased the odds of prevalent mild hearing loss (>25 40 dB HL), multivariate-adjusted [OR 1.37 (CI 1.04-1.81)]. Serum vitamin B-12, however, was not significantly associated with prevalent hearing loss. Serum folate, vitamin B-12, and tHcy concentrations were also not significantly associated with an increased risk of incident hearing loss. Serum concentrations of tHcy and folate were associated with age-related hearing loss cross sectionally, but no temporal links were observed, which could be due to insufficient study power. Further, large prospective studies will be required in the future to assess these associations. PMID- 20573943 TI - The use of dysprosium to measure endogenous zinc excretion in feces eliminates the necessity of complete fecal collections. AB - The secretion of endogenous zinc (Zn) into the gut and subsequent excretion in the feces is understood to play a major role in maintaining Zn homeostasis in humans. Therefore, the measurement of endogenous Zn losses in the feces (EFZ) can be an important aspect of the study of Zn metabolism and homeostasis. The methods currently used to measure EFZ have the disadvantage of requiring complete fecal collections over multiple days. We have investigated the use of dysprosium (Dy), a nonabsorbable rare earth metal, in a method of determining EFZ that does not require complete fecal collections and permits the measurement of EFZ from several fecal samples. The method was evaluated using data from a study of free living adult females in which Dy was administered 3-4 times/d over a period of 5 or 6 d to monitor completeness of fecal collections. The results did not differ from those obtained using an established isotope dilution method. We found that the measurement of the sample Dy:Zn ratio was useful for selecting samples for measurement. We conclude that the Dy method of determining EFZ is a valid and less burdensome alternative to current techniques. PMID- 20573944 TI - Individual isomers of conjugated linoleic acid reduce inflammation associated with established collagen-induced arthritis in DBA/1 mice. AB - Previously, dietary conjugated linoleic acid [(CLA), an equal mixture of cis-9, trans-11 (c9t11) and trans-10, cis-12 (t10c12) CLA isomers], was found to reduce inflammation in the murine collagen antibody-induced arthritis model, but less so in the murine collagen-induced arthritis (CIA) model, an arthritic model dependent upon acquired immunity. Because CLA is known to alter the acquired immune response, it was hypothesized that feeding CLA after the establishment of arthritis would reduce paw swelling in the CIA model. In this study, upon the establishment of arthritic symptoms, mice were randomized to the following dietary treatments: corn oil (CO) control (n = 6), 0.5% c9t11-CLA (n = 8), 0.5% t10c12-CLA (n = 6), or 1% combined CLA (1:1 c9t11:t10c12-CLA, n = 6). Paws were scored for severity of arthritis and measured for changes in thickness during an 84-d study period. Dietary c9t11- and combined-CLA similarly decreased the arthritic score (29%, P = 0.036, P = 0.049, respectively, when normalized to initial score) and paw thickness (0.11 mm, P = 0.027, P = 0.035, respectively) compared with CO. Dietary t10c12-CLA reduced the arthritic score (41%, P = 0.007 when normalized) and paw thickness (0.12 mm, P = 0.013) relative to CO. Reduced interleukin-1beta on d 7 and 21 for all CLA treatments (n = 3) relative to CO suggested that antiinflammatory effects of CLA isomers might work by common mechanisms of known pathways involved in chronic inflammation. In conclusion, dietary CLA reduced inflammation associated with CIA, and both c9t11-CLA and t10c12-CLA exhibited antiinflammatory effects. PMID- 20573945 TI - Dietary fiber intake is associated with reduced risk of mortality from cardiovascular disease among Japanese men and women. AB - Dietary fiber protects against coronary heart disease (CHD), but evidence in Asia is limited. We examined the association between dietary fiber intake and mortality from cardiovascular disease (CVD) in a Japanese population in a prospective study of 58,730 Japanese men and women aged 40-79 y in which dietary fiber intake was determined by a self-administered FFQ. The participants were followed up from 1988-1990 to the end of 2003. Hazard ratios (HR) and 95% CI of mortality were calculated per quintile of fiber intake. During the 14-y follow up, a total of 2080 CVD deaths (983 strokes, 422 CHD, and 675 other CVD) were documented. Total, insoluble, and soluble dietary fiber intakes were inversely associated with risk of mortality from CHD and total CVD for both men and women. For men, the multivariable HR (95% CI) for CHD in the highest vs. the lowest quintiles were 0.81 [(95% CI, 0.61-1.09); P-trend = 0.02], 0.48 [(95% CI, 0.27 0.84); P-trend < 0.001], and 0.71 [(95% CI, 0.41-0.97); P-trend = 0.04] for total, insoluble, and soluble fiber, respectively. The respective HR (95% CI) for women were 0.80 [(95% CI, 0.57-0.97); P-trend = 0.01], 0.49 [(95% CI, 0.27-0.86); P-trend = 0.004], and 0.72 [(95% CI, 0.34-0.99); P-trend = 0.03], respectively. For fiber sources, intakes of fruit and cereal fibers but not vegetable fiber were inversely associated with risk of mortality from CHD. In conclusion, dietary intakes of fiber, both insoluble and soluble fibers, and especially fruit and cereal fibers, may reduce risk of mortality from CHD. PMID- 20573947 TI - Automatic effects of alcohol and aggressive cues on aggressive thoughts and behaviors. AB - Numerous studies have shown that alcohol increases aggression. In this article it is proposed that the link between alcohol and aggression is so strong that mere exposure to alcohol-related cues will automatically activate aggressive thoughts and behaviors. Two experiments tested this automaticity theory of alcohol-related aggression. In Experiment 1, participants exposed to alcohol- or weapon-related primes made faster lexical decisions about aggression-related words than did participants exposed to neutral primes. In Experiment 2, participants exposed to alcohol- or aggression-related subliminal primes were more aggressive toward the experimenter than were participants exposed to neutral subliminal primes. In both experiments, the effects of alcohol-related cues were as strong as the effect of aggression-related cues on aggressive thoughts and behaviors. People do not need to drink a drop of alcohol to become aggressive; exposure to alcohol cues is enough to automatically increase aggression. PMID- 20573946 TI - Plasma arginine and ornithine are the main citrulline precursors in mice infused with arginine-free diets. AB - Dietary arginine is the main dietary precursor for citrulline synthesis, but it is not known if other precursors can compensate when arginine is absent in the diet. To address this question, the contributions of plasma and dietary precursors were determined by using multitracer protocols in conscious mice infused i.g. either an arginine-sufficient diet [Arg(+)] or an arginine-free diet [Arg(-)]. The plasma entry rate of citrulline and arginine did not differ between the 2 diet groups (156 +/- 6 and 564 +/- 30 micromol kg(-1) h(-1), respectively); however, the entry rate of ornithine was greater in the mice fed the Arg(+) than the Arg(-) diet (332 +/- 33 vs. 180 +/- 16 micromol kg(-1) h(-1)). There was a greater utilization of plasma ornithine for the synthesis of citrulline (49 +/- 4 vs. 36 +/- 3 micromol kg(-1) h(-1), 30 +/- 3% vs. 24 +/- 2% of citrulline entry rate) in the mice fed the Arg(-) diet than the Arg(+) diet. The utilization of plasma arginine did not differ between the 2 diet groups for citrulline synthesis, either through plasma ornithine (approximately 29 +/- 3 micromol kg( 1) h(-1)) or at the site of citrulline synthesis (approximately 12 +/- 3 micromol kg(-1) h(-1)). The contribution of dietary proline to the synthesis of citrulline was mainly at the site of citrulline production (17 +/- 1 micromol kg(-1) h(-1)), rather than through plasma ornithine (5 +/- 0.4 micromol kg(-1) h(-1)). Dietary glutamine was utilized only at the site of citrulline synthesis (4 +/- 0.2 micromol kg(-1) h(-1)). Dietary glutamine and proline made a greater contribution to the synthesis of citrulline in mice fed the Arg(-) diet but remained minor sources for citrulline production. Plasma arginine and ornithine are able to support citrulline synthesis during arginine-free feeding. PMID- 20573948 TI - A signal detection analysis of chronic attachment anxiety at speed dating: being unpopular is only the first part of the problem. AB - Initiating a romantic relationship invokes an approach-avoidance conflict between the desire for affiliation and the fear of rejection; optimally, people should selectively approach potential partners who reciprocate their interest. This may be difficult for anxiously attached people: They may be unpopular, and their ambivalence could lead to either a fearfully selective approach at the cost of missed opportunities or an unselective, indiscriminate approach at the cost of increasing rejection. Using a speed-dating paradigm, data were collected from 116 participants, and a signal detection framework was applied to examine the outcomes. For anxious participants, speed-dating attendance was motivated by loneliness. At speed dating, they were unpopular and unselective; they missed fewer opportunities but made more failed attempts. Anxious men made fewer matches than nonanxious men, whereas anxious women were buffered by having a response bias toward saying "yes" to potential partners. Attachment anxiety predicted outcomes above and beyond the powerful impact of attractiveness. PMID- 20573949 TI - Predictors of physical activity patterns across adulthood: a growth curve analysis. AB - Activity level is a core but understudied individual difference. Understanding patterns of physical activity over long periods may be key to understanding why some individuals develop healthy lifestyles. The present study transformed qualitative information from the Terman Life Cycle Study to examine patterns of leisure time physical activity across four decades (1936-1972). Activities were converted into metabolic equivalent (MET) ratings, and then activity patterns, individual variation, and child and adult personality predictors of differing trajectories were examined using growth curve modeling. For overall activity, a quadratic model fit best, with decelerating decline as people aged. Males were consistently more active than females. Much individual variation was present, but childhood energy and sociability, and adult extraversion and neuroticism predicted average activity levels and change. Results suggest that physical activity needs to be understood within the context of the individual's personality and long-term trajectory, not merely current motivations. PMID- 20573950 TI - Hepatic FoxO1 ablation exacerbates lipid abnormalities during hyperglycemia. AB - Patients with diabetes suffer disproportionately from impaired lipid metabolism and cardiovascular disease, but the relevant roles of insulin resistance and hyperglycemia in these processes are unclear. Transcription factor FoxO1 is regulated dually by insulin and nutrients. In this study, we addressed the hypothesis that, in addition to its established role to regulate hepatic glucose production, FoxO1 controls aspects of lipid metabolism in the diabetic liver. Mice with a liver-specific deletion of FoxO1 (L-FoxO1) and their control littermates were rendered hyperglycemic by streptozotocin administration. Subsequently, we monitored serum lipids, liver VLDL secretion, and hepatic expression of genes related to lipid metabolism. Hepatic FoxO1 ablation resulted in increased VLDL secretion, increased cholesterol, and increased plasma free fatty acids, three hallmarks of the diabetic state. l-FoxO1 mice expressed increased levels of SREBP-2 and FGF21 without affecting lipogenic genes. We propose that FoxO1 fine tunes lipolysis through its actions on FGF21 and that hepatic FoxO1 ablation increases availability of substrates for hepatic triglyceride and cholesterol synthesis and VLDL secretion. The implications of these findings are that FoxO1 protects against excessive hepatic lipid production during hyperglycemia and that its inhibition by intensive insulin treatment may exacerbate paradoxically the lipid abnormalities of diabetes. PMID- 20573951 TI - Retinoic acid induces expression of the thyroid hormone transporter, monocarboxylate transporter 8 (Mct8). AB - Retinoic acid (RA) and thyroid hormone are critical for differentiation and organogenesis in the embryo. Mct8 (monocarboxylate transporter 8), expressed predominantly in the brain and placenta, mediates thyroid hormone uptake from the circulation and is required for normal neural development. RA induces differentiation of F9 mouse teratocarcinoma cells toward neurons as well as extraembryonal endoderm. We hypothesized that Mct8 is functionally expressed in F9 cells and induced by RA. All-trans-RA (tRA) and other RA receptor (RAR) agonists dramatically (>300-fold) induced Mct8. tRA treatment significantly increased uptake of triiodothyronine and thyroxine (4.1- and 4.3-fold, respectively), which was abolished by a selective Mct8 inhibitor, bromosulfophthalein. Sequence inspection of the Mct8 promoter region and 5'-rapid amplification of cDNA ends PCR analysis in F9 cells identified 11 transcription start sites and a proximal Sp1 site but no TATA box. tRA significantly enhanced Mct8 promoter activity through a consensus RA-responsive element located 6.6 kilobases upstream of the coding region. A chromatin immunoprecipitation assay demonstrated binding of RAR and retinoid X receptor to the RA response element. The promotion of thyroid hormone uptake through the transcriptional up-regulation of Mct8 by RAR is likely to be important for extraembryonic endoderm development and neural differentiation. This finding demonstrates cross-talk between RA signaling and thyroid hormone signaling in early development at the level of the thyroid hormone transporter. PMID- 20573952 TI - Mechanism of concerted inhibition of alpha2beta2-type hetero-oligomeric aspartate kinase from Corynebacterium glutamicum. AB - Aspartate kinase (AK) is the first and committed enzyme of the biosynthetic pathway producing aspartate family amino acids, lysine, threonine, and methionine. AK from Corynebacterium glutamicum (CgAK), a bacterium used for industrial fermentation of amino acids, including glutamate and lysine, is inhibited by lysine and threonine in a concerted manner. To elucidate the mechanism of this unique regulation in CgAK, we determined the crystal structures in several forms: an inhibitory form complexed with both lysine and threonine, an active form complexed with only threonine, and a feedback inhibition-resistant mutant (S301F) complexed with both lysine and threonine. CgAK has a characteristic alpha(2)beta(2)-type heterotetrameric structure made up of two alpha subunits and two beta subunits. Comparison of the crystal structures between inhibitory and active forms revealed that binding inhibitors causes a conformational change to a closed inhibitory form, and the interaction between the catalytic domain in the alpha subunit and beta subunit (regulatory subunit) is a key event for stabilizing the inhibitory form. This study shows not only the first crystal structures of alpha(2)beta(2)-type AK but also the mechanism of concerted inhibition in CgAK. PMID- 20573953 TI - Structure and mutagenesis of neural cell adhesion molecule domains: evidence for flexibility in the placement of polysialic acid attachment sites. AB - The addition of alpha2,8-polysialic acid to the N-glycans of the neural cell adhesion molecule, NCAM, is critical for brain development and plays roles in synaptic plasticity, learning and memory, neuronal regeneration, and the growth and invasiveness of cancer cells. Our previous work indicates that the polysialylation of two N-glycans located on the fifth immunoglobulin domain (Ig5) of NCAM requires the presence of specific sequences in the adjacent fibronectin type III repeat (FN1). To understand the relationship of these two domains, we have solved the crystal structure of the NCAM Ig5-FN1 tandem. Unexpectedly, the structure reveals that the sites of Ig5 polysialylation are on the opposite face from the FN1 residues previously found to be critical for N-glycan polysialylation, suggesting that the Ig5-FN1 domain relationship may be flexible and/or that there is flexibility in the placement of Ig5 glycosylation sites for polysialylation. To test the latter possibility, new Ig5 glycosylation sites were engineered and their polysialylation tested. We observed some flexibility in glycosylation site location for polysialylation and demonstrate that the lack of polysialylation of a glycan attached to Asn-423 may be in part related to a lack of terminal processing. The data also suggest that, although the polysialyltransferases do not require the Ig5 domain for NCAM recognition, their ability to engage with this domain is necessary for polysialylation to occur on Ig5 N-glycans. PMID- 20573954 TI - Structural insights into the catalytic mechanism of bacterial guanosine-diphospho D-mannose pyrophosphorylase and its regulation by divalent ions. AB - GMP catalyzes the formation of GDP-Man, a fundamental precursor for protein glycosylation and bacterial cell wall and capsular polysaccharide biosynthesis. Crystal structures of GMP from the thermophilic bacterium Thermotoga maritima in the apo form, in complex with the substrates mannose-1-phosphate or GTP and bound with the end product GDP-Man in the presence of the essential divalent cation Mg(2+), were solved in the 2.1-2.8 A resolution range. The T. maritima GMP molecule is organized in two separate domains: a N-terminal Rossman fold-like domain and a C-terminal left-handed beta-helix domain. Two molecules associate into a dimer through a tail-to-tail arrangement of the C-terminal domains. Comparative analysis of the structures along with characterization of enzymatic parameters reveals the bases of substrate specificity of this class of sugar nucleotidyltransferases. In particular, substrate and product binding are associated with significant changes in the conformation of loop regions lining the active center and in the relative orientation of the two domains. Involvement of both the N- and C-terminal domains, coupled to the catalytic role of a bivalent metal ion, highlights the catalytic features of bacterial GMPs compared with other members of the pyrophosphorylase superfamily. PMID- 20573955 TI - Crystal structures of a group II chaperonin reveal the open and closed states associated with the protein folding cycle. AB - Chaperonins are large protein complexes consisting of two stacked multisubunit rings, which open and close in an ATP-dependent manner to create a protected environment for protein folding. Here, we describe the first crystal structure of a group II chaperonin in an open conformation. We have obtained structures of the archaeal chaperonin from Methanococcus maripaludis in both a peptide acceptor (open) state and a protein folding (closed) state. In contrast with group I chaperonins, in which the equatorial domains share a similar conformation between the open and closed states and the largest motions occurs at the intermediate and apical domains, the three domains of the archaeal chaperonin subunit reorient as a single rigid body. The large rotation observed from the open state to the closed state results in a 65% decrease of the folding chamber volume and creates a highly hydrophilic surface inside the cage. These results suggest a completely distinct closing mechanism in the group II chaperonins as compared with the group I chaperonins. PMID- 20573956 TI - Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. AB - Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a gamma-glutamylcysteine synthetase (gamma-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for gamma-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and gamma-GCS by simultaneous disruption of gr and gamma-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism. PMID- 20573957 TI - Neurons efficiently repair glutamate-induced oxidative DNA damage by a process involving CREB-mediated up-regulation of apurinic endonuclease 1. AB - Glutamate, the major excitatory neurotransmitter in the brain, activates receptors coupled to membrane depolarization and Ca(2+) influx that mediates functional responses of neurons including processes such as learning and memory. Here we show that reversible nuclear oxidative DNA damage occurs in cerebral cortical neurons in response to transient glutamate receptor activation using non toxic physiological levels of glutamate. This DNA damage was prevented by intracellular Ca(2+) chelation, the mitochondrial superoxide dismutase mimetic MnTMPyP (Mn-5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine chloride tetrakis(methochloride)), and blockade of the permeability transition pore. The repair of glutamate-induced DNA damage was associated with increased DNA repair activity and increased mRNA and protein levels of apurinic endonuclease 1 (APE1). APE1 knockdown induced accumulation of oxidative DNA damage after glutamate treatment, suggesting that APE1 is a key repair protein for glutamate-induced DNA damage. A cAMP-response element-binding protein (CREB) binding sequence is present in the Ape1 gene (encodes APE1 protein) promoter and treatment of neurons with a Ca(2+)/calmodulin-dependent kinase inhibitor (KN-93) blocked the ability of glutamate to induce CREB phosphorylation and APE1 expression. Selective depletion of CREB using RNA interference prevented glutamate-induced up regulation of APE1. Thus, glutamate receptor stimulation triggers Ca(2+)- and mitochondrial reactive oxygen species-mediated DNA damage that is then rapidly repaired by a mechanism involving Ca(2+)-induced, CREB-mediated APE1 expression. Our findings reveal a previously unknown ability of neurons to efficiently repair oxidative DNA lesions after transient activation of glutamate receptors. PMID- 20573958 TI - Serotonergic 5-HT(2B) receptor controls tissue-nonspecific alkaline phosphatase activity in osteoblasts via eicosanoids and phosphatidylinositol-specific phospholipase C. AB - In previous studies, we observed that mice knocked out for the serotonin-2B receptor (5-HT(2B)R) show defects in bone homeostasis. The present work focuses on the downstream targets relaying the anabolic function of this receptor in osteoblasts. A functional link between the 5-HT(2B)R and the activity of the tissue-nonspecific alkaline phosphatase (TNAP) is established using the C1 osteoprogenitor cell line. During C1 osteogenic differentiation, both 5-HT(2B)R and TNAP mRNA translations are delayed with respect to extracellular matrix deposition. Once the receptor is expressed, it constitutively controls TNAP activity at a post-translational level along the overall period of mineral deposition. Indeed, pharmacological inhibition of the 5-HT(2B)R intrinsic activity or shRNA-mediated 5-HT(2B)R knockdown prevents TNAP activation, but not its mRNA translation. In contrast, agonist stimulation of the receptor further increases TNAP activity during the initial mineralization phase. Building upon our previous observations that the 5-HT(2B)R couples with the phospholipase A2 pathway and prostaglandin production at the beginning of mineral deposition, we show that the 5-HT(2B)R controls leukotriene synthesis via phospholipase A2 at the terminal stages of C1 differentiation. These two 5-HT(2B)R-dependent eicosanoid productions delineate distinct time windows of TNAP regulation during the osteogenic program. Finally, prostaglandins or leukotrienes are shown to relay the post-translational activation of TNAP via stimulation of the phosphatidylinositol-specific phospholipase C. In agreement with the above findings, primary calvarial osteoblasts from 5-HT(2B)R-null mice exhibit defects in TNAP activity. PMID- 20573959 TI - Nix is critical to two distinct phases of mitophagy, reactive oxygen species mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. AB - Damaged mitochondria can be eliminated by autophagy, i.e. mitophagy, which is important for cellular homeostasis and cell survival. Despite the fact that a number of factors have been found to be important for mitophagy in mammalian cells, their individual roles in the process had not been clearly defined. Parkin is a ubiquitin-protein isopeptide ligase able to translocate to the mitochondria that are to be removed. We showed here in a chemical hypoxia model of mitophagy induced by an uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP) that Parkin translocation resulted in mitochondrial ubiquitination and p62 recruitment to the mitochondria. Small inhibitory RNA-mediated knockdown of p62 significantly diminished mitochondrial recognition by the autophagy machinery and the subsequent elimination. Thus Parkin, ubiquitin, and p62 function in preparing mitochondria for mitophagy, here referred to as mitochondrial priming. However, these molecules were not required for the induction of autophagy machinery. Neither Parkin nor p62 seemed to affect autophagy induction by CCCP. Instead, we found that Nix was required for the autophagy induction. Nix promoted CCCP induced mitochondrial depolarization and reactive oxygen species generation, which inhibited mTOR signaling and activated autophagy. Nix also contributed to mitochondrial priming by controlling the mitochondrial translocation of Parkin, although reactive oxygen species generation was not involved in this step. Deletion of the C-terminal membrane targeting sequence but not mutations in the BH3 domain disabled Nix for these functions. Our work thus distinguished the molecular events responsible for the different phases of mitophagy and placed Nix upstream of the events. PMID- 20573960 TI - Interruption of cenph causes mitotic failure and embryonic death, and its haploinsufficiency suppresses cancer in zebrafish. AB - Kinetochore proteins associate with centromeric DNA and spindle microtubules and play essential roles in chromosome segregation during mitosis. In this study, we uncovered a zebrafish mutant, stagnant and curly (stac), that carries the Tol2 transposon element inserted at the kinetochore protein H (cenph) locus. Mutant embryos exhibit discernible cell death as early as 20 hours postfertilization, extensive apoptosis, and upward curly tail during the pharyngula period and deform around 5 days postfertilization. The stac mutant phenotype can be rescued by cenph mRNA overexpression and mimicked by cenph knockdown with antisense morpholinos, suggesting the responsibility of cenph deficiency for stac mutants. We demonstrate that the intrinsic apoptosis pathway is hyperactivated in stac mutants and that p53 knockdown partially blocks excess apoptosis in stac mutants. Mitotic cells in stac mutants show chromosome missegregation and are usually arrested in G(2)/M phase. Furthermore, compared with wild type siblings, heterozygous stac fish develop invasive tumors at a dramatically reduced rate, suggesting a reduced cancer risk. Taken together, our findings uncover an essential role of cenph in mitosis and embryonic development and its association with tumor development. PMID- 20573961 TI - Beta,beta-carotene decreases peroxisome proliferator receptor gamma activity and reduces lipid storage capacity of adipocytes in a beta,beta-carotene oxygenase 1 dependent manner. AB - Increasing evidence has been provided for a connection between retinoid metabolism and the activity of peroxisome proliferator receptors (Ppars) in the control of body fat reserves. Two different precursors for retinoids exist in the diet as preformed vitamin A (all-trans-retinol) and provitamin A (beta,beta carotene). For retinoid production, beta,beta-carotene is converted to retinaldehyde by beta,beta-carotene monooxygenase 1 (Bcmo1). Previous analysis showed that Bcmo1 knock-out mice develop dyslipidemia and are more susceptible to diet-induced obesity. However, the role of Bcmo1 for adipocyte retinoid metabolism has yet not been well defined. Here, we showed that Bcmo1 mRNA and protein expression are induced during adipogenesis in NIH 3T3-L1 cells. In mature adipocytes, beta,beta-carotene but not all-trans-retinol was metabolized to retinoic acid (RA). RA decreased the expression of Ppar gamma and CCAAT/enhancer binding protein alpha, key lipogenic transcription factors, and reduced the lipid content of mature adipocytes. This process was inhibited by the retinoic acid receptor antagonist LE450, showing that it involves canonical retinoid signaling. Accordingly, gavage of beta,beta-carotene but not all-trans-retinol induced retinoid signaling and decreased Ppar gamma expression in white adipose tissue of vitamin A-deficient mice. Our study identifies beta,beta-carotene as a critical physiological precursor for RA production in adipocytes and implicates provitamin A as a dietary regulator of body fat reserves. PMID- 20573962 TI - Transcriptional control of the Bradyrhizobium japonicum irr gene requires repression by fur and Antirepression by Irr. AB - Bradyrhizobium japonicum Fur mediates manganese-responsive transcriptional control of the mntH gene independently of iron, but it also has been implicated in iron-dependent regulation of the irr gene. Thus, we sought to address the apparent discrepancy in Fur responsiveness to metals. Irr is a transcriptional regulator found in iron-limited cells. Here, we show that irr gene mRNA was regulated by both iron and manganese, and repression occurred only in the presence of both metals. Under these conditions, Fur occupied the irr promoter in vivo in the parent strain, and irr mRNA expression was derepressed in a fur mutant. Under low iron conditions, the irr promoter was occupied by Irr, but not by Fur, and control by manganese was lost. Fur occupancy of the irr promoter was dependent on manganese, but not iron, in an irr mutant, suggesting that Irr normally interferes with Fur binding. Correspondingly, regulation of irr mRNA was dependent only on manganese in the irr strain. The Irr binding site within the irr promoter partially overlaps the Fur binding site. DNase I footprinting analysis showed that Irr interfered with Fur binding in vitro. In addition, Fur repression of transcription from the irr promoter in vitro was relieved by Irr. We conclude that Fur mediates manganese-dependent repression of irr transcription and that Irr acts as an antirepressor under iron limitation by preventing Fur binding to the promoter. PMID- 20573963 TI - Neurotoxic mutants of the prion protein induce spontaneous ionic currents in cultured cells. AB - The mechanisms by which prions kill neurons and the role of the cellular prion protein in this process are enigmatic. Insight into these questions is provided by the neurodegenerative phenotypes of transgenic mice expressing prion protein (PrP) molecules with deletions of conserved amino acids in the central region. We report here that expression in transfected cells of the most toxic of these PrP deletion mutants (Delta105-125) induces large, spontaneous ionic currents that can be detected by patch-clamping techniques. These currents are produced by relatively non-selective, cation-permeable channels or pores in the cell membrane and can be silenced by overexpression of wild-type PrP, as well as by treatment with a sulfated glycosaminoglycan. Similar currents are induced by PrP molecules carrying several different point mutations in the central region that cause familial prion diseases in humans. The ionic currents described here are distinct from those produced in artificial lipid membranes by synthetic peptides derived from the PrP sequence because they are induced by membrane-anchored forms of PrP that are synthesized by cells and that are found in vivo. Our results indicate that the neurotoxicity of some mutant forms of PrP is attributable to enhanced ion channel activity and that wild-type PrP possesses a channel-silencing activity. Drugs that block PrP-associated channels or pores may therefore represent novel therapeutic agents for treatment of patients with prion diseases. PMID- 20573964 TI - Membrane region M2C2 in subunit KtrB of the K+ uptake system KtrAB from Vibrio alginolyticus forms a flexible gate controlling K+ flux: an electron paramagnetic resonance study. AB - Transmembrane stretch M(2C) from the bacterial K(+)-translocating protein KtrB is unusually long. In its middle part, termed M(2C2), it contains several small and polar amino acids. This region is flanked by the two alpha-helices M(2C1) and M(2C3) and may form a flexible gate at the cytoplasmic side of the membrane controlling K(+) translocation. In this study, we provide experimental evidence for this notion by using continuous wave and pulse EPR measurements of single and double spin-labeled cysteine variants of KtrB. Most of the spin-labeled residues in M(2C2) were shown to be immobile, pointing to a compact structure. However, the high polarity revealed for the microenvironment of residue positions 317, 318, and 327 indicated the existence of a water-accessible cavity. Upon the addition of K(+) ions, M(2C2) residue Thr-318R1 (R1 indicates the bound spin label) moved with respect to M(2B) residue Asp-222R1 and M(2C3) residue Val-331R1 but not with respect to M(2C1) residue Met-311R1. Based on distances determined between spin-labeled residues of double-labeled variants of KtrB in the presence and absence of K(+) ions, structural models of the open and closed conformations were developed. PMID- 20573965 TI - Accessibility of cholesterol in endoplasmic reticulum membranes and activation of SREBP-2 switch abruptly at a common cholesterol threshold. AB - Recent studies have shown that cooperative interactions in endoplasmic reticulum (ER) membranes between Scap, cholesterol, and Insig result in switch-like control over activation of SREBP-2 transcription factors. This allows cells to rapidly adjust rates of cholesterol synthesis and uptake in response to even slight deviations from physiological set-point levels, thereby ensuring cholesterol homeostasis. In the present study we directly probe for the accessibility of cholesterol in purified ER membranes. Using a soluble cholesterol-binding bacterial toxin, perfringolysin O, we show that cholesterol accessibility increases abruptly at ~5 mol % ER cholesterol, the same concentration at which SREBP-2 activation is halted. This switch-like change in cholesterol accessibility is observed not only in purified ER membranes but also in liposomes made from ER lipid extracts. The accessibility of cholesterol in membranes is related to its chemical activity. Complex formation between cholesterol and some ER phospholipids can result in sharp changes in cholesterol chemical activity and its accessibility to perfringolysin O or membrane sensors like Scap. The control of the availability of the cholesterol ligand to participate in cooperative Scap/cholesterol/Insig interactions further sharpens the sensitive switch that exerts precise control over cholesterol levels in cell membranes. PMID- 20573966 TI - Electrophysiological and chemical properties in subclassified acutely dissociated cells of rat trigeminal ganglion by current signatures. AB - In the present study, we subclassified acutely dissociated trigeminal ganglion (TRG) cells of rats using a current signature method in whole cell patch-clamp recordings. Using modified criteria for cell classification for the dorsal root ganglion (DRG), TRG cells were subclassified into nine cell types: 1-5, 7-9, and 13. Types 1, 3, and 7 were in the small cell groups (15-24 MUm); types 4, 5, and 8-13 were in the medium cell groups (25-38 MUm); and type 2 was a mixed group of both cell sizes. Types 1-3, 5, and 7 showed high-input resistance and types 1, 2, and 7 showed more depolarized resting membrane potentials. Types 1, 2, and 5-13 expressed long-duration action potentials (APs), but types 3 and 4 expressed short-duration APs. Sensitivities to capsaicin, protons, and adenosine 5' triphosphate (ATP) in TRG cell types largely corresponded to DRG cell types. However, different from the matched DRG types, half of TRG type 1 cells were capsaicin insensitive, showing desensitizing proton-induced currents, and types 5, 7, and 9 exhibited slow-desensitizing ATP-induced currents. Types 4, 5, and 8 13 had nicotine sensitivity, but the other cell types were insensitive. These results indicate that the "current signatures" classification is a useful means to separate TRG cells into internally homogeneous subpopulations that were distinct from other cell types. Furthermore, the data suggest some specific differences in the chemical responsiveness of some cell types between the TRG and DRG. PMID- 20573967 TI - Modulation of voltage-gated ion channels in rat retinal ganglion cells mediated by somatostatin receptor subtype 4. AB - Somatostatin (somatotropin release-inhibiting factor [SRIF]) is known to modulate the excitability of retinal ganglion cells, but the membrane mechanisms responsible and the extent to which intracellular calcium signaling is affected have not been determined. We show that somatostatin receptor subtype 4 (sst(4)) is expressed specifically in rat ganglion cells and that the generation of repetitive action potentials by isolated ganglion cells is reduced in the presence of L-803,087, a selective sst(4) agonist (10 nM). Under voltage clamp, L 803,087 increased outward K(+) currents by 51.1 +/- 13.1% at 0 mV and suppressed Ca(2+) channel currents by 32.5 +/- 9.4% at -10 mV in whole cell patch-clamped ganglion cells. The N-type Ca(2+) channel blocker omega-conotoxin GVIA (CTX, 1 MUM) reduced L-type Ca(2+) current (I(Ca)) in ganglion cells by 43.5 +/- 7.2% at 10 mV, after which addition of L-803,087 further reduced I(Ca) by 28.0 +/- 16.0% . In contrast, ganglion cells treated first with nifedipine (NIF, 10 MUM), which blocked 46.1 +/- 3.5% of the control current at -10 mV, did not undergo any further reduction in I(Ca) in the presence of L-803,087 (-3.5 +/- 3.8% vs. NIF), showing that stimulation of sst(4) reduces Ca(2+) influx through L-type Ca(2+) channels. To assess the effects of sst(4) stimulation on intracellular Ca(2+) levels ([Ca(2+)](i)) in ganglion cells, fura-2 was used to measure changes in [Ca(2+)](i) in response to depolarization induced by elevated [K(+)](o). [Ca(2+)](i) was increased to a lesser extent (86%) in the presence of L-803,087 compared with recordings made in the absence of the sst(4) agonist and this effect was blocked by NIF (10 MUM). Suppression of spiking and Ca(2+) signaling via sst(4) may contribute to the reported neuroprotective actions of somatostatin and promote ganglion cell survival following ischemia and axonal trauma. PMID- 20573968 TI - Detection of minute temperature transients by thermosensitive neurons in ants. AB - The antennae of leaf-cutting ants are equipped with sensilla coeloconica that house three receptor neurons, one of which is thermosensitive. Using convective heat (air at different temperatures), we investigated the physiological characteristics of the thermosensitive neuron associated with the sensilla coeloconica in the leaf-cutting ant Atta vollenweideri. The thermosensitive neuron very quickly responds to a drop in temperature with a brief phasic increase (50 ms) in spike rate and thus classifies as cold receptor (ambient temperature = 24 degrees C). The short latency and the brief phasic response enable the thermosensitive neuron to follow temperature transients up to an estimated frequency of around 5 Hz. Although the neuron responds as a cold receptor, it is extremely sensitive to warm stimuli. A temperature increase of only 0.005 degrees C already leads to a pronounced decrease in the resting activity of the thermosensitive neuron. Through sensory adaptation, the sensitivity to temperature transients is maintained over a wide range of ambient temperatures (18-30 degrees C). We conclude that the thermosensitive neuron of the sensilla coeloconica is adapted to detect minute temperature transients, providing the ants with thermal information of their microenvironment, which they may use for orientation. PMID- 20573969 TI - Role of intrinsic properties in Drosophila motoneuron recruitment during fictive crawling. AB - Motoneurons in most organisms conserve a division into low-threshold and high threshold types that are responsible for generating powerful and precise movements. Drosophila 1b and 1s motoneurons may be analogous to low-threshold and high-threshold neurons, respectively, based on data obtained at the neuromuscular junction, although there is little information available on intrinsic properties or recruitment during behavior. Therefore in situ whole cell patch-clamp recordings were used to compare parameters of 1b and 1s motoneurons in Drosophila larvae. We find that resting membrane potential, voltage threshold, and delay-to spike distinguish 1b from 1s motoneurons. The longer delay-to-spike in 1s motoneurons is a result of the shal-encoded A-type K(+) current. Functional differences between 1b and 1s motoneurons are behaviorally relevant because a higher threshold and longer delay-to-spike are observed in MNISN-1s in pairwise whole cell recordings of synaptically evoked activity during bouts of fictive locomotion. PMID- 20573970 TI - Feedback and feedforward locomotor adaptations to ankle-foot load in people with incomplete spinal cord injury. AB - Humans with spinal cord injury (SCI) modulate locomotor output in response to limb load. Understanding the neural control mechanisms responsible for locomotor adaptation could provide a framework for selecting effective interventions. We quantified feedback and feedforward locomotor adaptations to limb load modulations in people with incomplete SCI. While subjects airstepped (stepping performed with kinematic assistance and 100% bodyweight support), a powered orthosis created a dorisflexor torque during the "stance phase" of select steps producing highly controlled ankle-load perturbations. When given repetitive, stance phase ankle-load, the increase in hip extension work, 0.27 J/kg above baseline (no ankle-load airstepping), was greater than the response to ankle-load applied during a single step, 0.14 J/kg (P = 0.029). This finding suggests that, at the hip, subjects produced both feedforward and feedback locomotor modulations. We estimate that, at the hip, the locomotor response to repetitive ankle-load was modulated almost equally by ongoing feedback and feedforward adaptations. The majority of subjects also showed after-effects in hip kinetic patterns that lasted 3 min in response to repetitive loading, providing additional evidence of feedforward locomotor adaptations. The magnitude of the after-effect was proportional to the response to repetitive ankle-foot load (R(2) = 0.92). In contrast, increases in soleus EMG amplitude were not different during repetitive and single-step ankle-load exposure, suggesting that ankle locomotor modulations were predominately feedback-based. Although subjects made both feedback and feedforward locomotor adaptations to changes in ankle-load, between subject variations suggest that walking function may be related to the ability to make feedforward adaptations. PMID- 20573971 TI - Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern. AB - The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord. PMID- 20573972 TI - Reliability of long-interval cortical inhibition in healthy human subjects: a TMS EEG study. AB - Cortical inhibition (CI) is measured by transcranial magnetic stimulation (TMS) combined with electromyography (EMG) through long-interval CI (LICI) and cortical silent period (CSP) paradigms. Recently, we illustrated that LICI can be measured from the dorsolateral prefrontal cortex (DLPFC) through combined TMS with electroencephalography (EEG). We further demonstrated that LICI had different effects on cortical oscillations in the DLPFC compared with motor cortex. The purpose of this study was to establish the validity and reliability of TMS-EEG indices of CI and to replicate our previous findings in an extended sample. The validity of TMS-EEG was examined by evaluating its relationship to standard EMG measures of LICI and the CSP in the left motor cortex in 36 and 16 subjects, respectively. Test-retest reliability was examined in 14 subjects who returned for a repeat session within 7 days of the first session. LICI was applied to the left DLPFC in 30 subjects to compare LICI in the DLPFC with that in the motor cortex. In the motor cortex, EEG measures of LICI correlated with EMG measures of LICI and CSP. All indices of LICI showed high test-retest reliability in motor cortex and DLPFC. Gamma and beta oscillations were significantly inhibited in the DLPFC but not in the motor cortex, confirming previous findings in an extended sample. These findings demonstrate that indexing LICI through TMS combined with EEG is a valid and reliable method to evaluate inhibition from motor and prefrontal regions. PMID- 20573973 TI - Sensory learning differentially affects GABAergic tonic currents in excitatory neurons and fast spiking interneurons in layer 4 of mouse barrel cortex. AB - Pairing tactile stimulation of whiskers with a tail shock is known to result in expansion of cortical representation of stimulated vibrissae and in the increase in synaptic GABAergic transmission. However, the impact of such sensory learning in classical conditioning paradigm on GABAergic tonic currents has not been addressed. To this end, we performed whole cell patch-clamp slice recordings of tonic currents from neurons (excitatory regular spiking, regular spiking nonpyramidal, and fast spiking interneurons) of layer 4 of the barrel cortex from naive and trained mice. Interestingly, endogenous tonic GABAergic currents measured from the excitatory neurons in the cortical representation of "trained" vibrissae were larger than in the "naive" or pseudoconditioned ones. On the contrary, sensory learning markedly reduced tonic currents in the fast spiking interneurons but not in regular spiking nonpyramidal neurons. Changes of tonic currents were accompanied by changes in the input resistances-decrease in regular spiking and increase in fast spiking neurons, respectively. Applications of nipecotic acid, a GABA uptake blocker, enhanced the tonic currents, but the impact of the sensory learning remained qualitatively the same as in the case of the tonic currents. Similar to endogenous tonic currents, sensory learning enhanced currents induced by THIP (superagonist for delta subunit-containing GABA(A) receptors) in regular spiking neurons, whereas the opposite was observed for the fast spiking interneurons. In conclusion, our data show that the sensory learning strongly affects the GABAergic tonic currents in a cell-specific manner and suggest that the underlying mechanism involves regulation of expression of delta subunit-containing GABA(A) receptors. PMID- 20573975 TI - Sensorimotor mapping for anticipatory grip force modulation. AB - During object manipulation, predictive grip force modulation allows compensation for inertial forces induced by the object's acceleration. This coupling between grip force (GF) and load force (LF) during voluntary movements has demonstrated high levels of complexity, adaptability, and flexibility under many loading conditions in a broad range of experimental studies. The association between GF and LF indicates the presence of internal models underlying predictive GF control. The present experiment sought to identify the variables taken into account during GF modulation at the initiation of a movement. Twenty subjects performed discrete point-to-point movements under normal and hypergravity conditions induced by parabolic flights. Two control experiments performed under normal gravitational conditions compared the observed effect of the increase in gravity with the effects of a change in movement kinematics and a change in mass. In hypergravity, subjects responded accurately to the increase in weight during stationary holding but overestimated inertial loads. During dynamic phases, the relationship between GF and LF under hypergravity varied in a manner similar to the control test in which object mass was increased, whereas a change in movement kinematics could not reproduce this result. We suggest that the subjects' strategy for anticipatory GF modulation is based on sensorimotor mapping that combines the perception of the weight encoded during stationary holding with an internal representation of the movement kinematics. In particular, such a combination reflects a prior knowledge of the unequivocal relationship linking mass, weight, and loads under the invariant gravitational context experienced on Earth. PMID- 20573974 TI - Dissociating bottom-up and top-down processes in a manual stimulus-response compatibility task. AB - Speed and accuracy of motor responses to lateralized stimuli are influenced by the spatial overlap between stimulus location and required response. Responses showing high spatial overlap with peripheral cues benefit from a bottom-up driven enhancement of attention to the respective location, whereas low overlap requires top-down modulated reorienting of resources. Here we investigated the interaction between these two processes using a spatial stimulus-response compatibility task. Subjects had to react to lateralized visual stimuli with a button press using either the ipsilateral (congruent condition) or the contralateral (incongruent condition) index finger. Stimulus-driven bottom-up processes were associated with significant contralateral activation in V5, the intraparietal sulcus (IPS) and the premotor cortex (PMC). Incongruent versus congruent responses evoked significant activation in bilateral IPS and PMC, highly overlapping with the activations found for stimulus-driven bottom-up processes, as well as additional activation in bilateral anterior insula and right dorsolateral prefrontal cortex (DLPFC) and temporoparietal junction (TPJ). Moreover, a region anterior to the bottom-up driven activation in the IPS was associated with top-down modulated directionality-specific reorienting of motor attention during incongruent motor responses. Based on these results, we propose that stimulus-driven activation of contralateral IPS and PMC represent key neuronal substrates for the behavioral advantage observed when reacting toward a congruently lateralized stimulus. Additional activation in bilateral insula and right DLPFC and TPJ during incongruent responses should reflect top-down control mechanisms mediating contextual (i.e., task) demands. Furthermore, this study provides evidence for both overlapping and disparate substrates of bottom-up and top-down modulated attentional processes in the IPS. PMID- 20573976 TI - External urethral sphincter motoneuron properties in adult female rats studied in vitro. AB - The external urethral sphincter (EUS) muscle plays a crucial role in lower urinary tract function: its activation helps maintain continence, whereas its relaxation contributes to micturition. To determine how the intrinsic properties of its motoneurons contribute to its physiological function, we have obtained intracellular current-clamp recordings from 49 EUS motoneurons in acutely isolated spinal cord slices from adult female rats. In all, 45% of EUS motoneurons fired spontaneously and steadily (average rate = 12-27 pulses/s). EUS motoneurons were highly excitable, having lower rheobase, higher input resistance, and smaller threshold depolarization than those of rat hindlimb motoneurons recorded in vitro. Correlations between these properties and afterhyperpolarization half-decay time are consistent with EUS motoneurons having characteristics of both fast and slow motor unit types. EUS motoneurons with a slow-like spectrum of properties exhibited spontaneous firing more often than those with fast-like characteristics. During triangular current ramp-induced repetitive firing, recruitment typically occurred at lower current levels than those at derecruitment, although the opposite pattern occurred in 10% of EUS motoneurons. This percentage was likely underestimated due to firing rate adaptation. These findings are consistent with the presence of a basal level of persistent inward current (PIC) in at least some EUS motoneurons. The low EUS motoneuron current and voltage thresholds make them readily recruitable, rendering them well suited to their physiological role in continence. The expression of firing behaviors consistent with PIC activation in this highly reduced preparation raises the possibility that in the intact animal, PICs contribute to urinary function not only through neuromodulator-dependent but also through neuromodulator-independent mechanisms. PMID- 20573977 TI - Regulation of exocytosis and fusion pores by synaptotagmin-effector interactions. AB - Synaptotagmin (syt) serves as a Ca(2+) sensor in the release of neurotransmitters and hormones. This function depends on the ability of syt to interact with other molecules. Syt binds to phosphatidylserine (PS)-containing lipid bilayers as well as to soluble N-ethylmaleimide sensitive factor receptors (SNAREs) and promotes SNARE assembly. All these interactions are regulated by Ca(2+), but their specific roles in distinct kinetic steps of exocytosis are not well understood. To explore these questions we used amperometry recording from PC12 cells to investigate the kinetics of exocytosis. Syt isoforms and syt I mutants were overexpressed to perturb syt-PS and syt-SNARE interactions to varying degrees and evaluate the effects on fusion event frequency and the rates of fusion pore transitions. Syt I produced more rapid dilation of fusion pores than syt VII or syt IX, consistent with its role in synchronous synaptic release. Stronger syt-PS interactions were accompanied by a higher frequency of fusion events and more stable fusion pores. By contrast, syt-SNARE interactions and syt-induced SNARE assembly were uncorrelated with rates of exocytosis. This associates the syt-PS interaction with two distinct kinetic steps in Ca(2+) triggered exocytosis and supports a role for the syt-PS interaction in stabilizing open fusion pores. PMID- 20573978 TI - Phosphatidic acid plays a regulatory role in clathrin-mediated endocytosis. AB - Clathrin-mediated endocytosis (CME) is the main route of internalization of receptor-ligand complexes. Relatively little is known about the role of specific lipids in CME, in particular that of phosphatidic acid (PA). We examined the effect of altering cellular PA levels on CME by manipulating the activities and/or levels of either phospholipase D (PLD1 and PLD2) or diacylglycerol kinase (DGK), two enzyme classes involved in PA production. DGK inhibition resulted in a dramatic reduction of cellular PA, measured directly using an enzyme-coupled reaction, which resulted in a decreased rate of EGFR internalization measured biochemically. This corresponded to a decreased rate of clathrin-coated pit (CCP) initiation and increased lifetimes of productive CCPs, as determined by quantitative live-cell total internal reflection fluorescence microscopy. Unexpectedly, PLD inhibition caused an increase in cellular PA, suggesting that PLD activity negatively regulates PA synthesis by other more productive pathways. Consistent with opposite effects on cellular PA levels, PLD inhibition had opposite effects on EGFR internalization and CCP dynamics, compared with DGK inhibition. Importantly, the constitutive internalization of transferrin receptors was unaffected by either treatment. These findings demonstrate that PA plays a regulatory rather than obligatory role in CME and differentially regulates ligand-stimulated CME of EGFR. PMID- 20573979 TI - WASP family proteins: their evolution and its physiological implications. AB - WASP family proteins control actin polymerization by activating the Arp2/3 complex. Several subfamilies exist, but their regulation and physiological roles are not well understood, nor is it even known if all subfamilies have been identified. Our extensive search reveals few novel WASP family proteins. The WASP, WASH, and SCAR/WAVE subfamilies are evolutionarily ancient, with WASH the most universally present, whereas WHAMM/JMY first appears in invertebrates. An unusual Dictyostelium WASP homologue that has lost the WH1 domain has retained its function in clathrin-mediated endocytosis, demonstrating that WASPs can function with a remarkably diverse domain topology. The WASH and SCAR/WAVE regulatory complexes are much more rigidly maintained; their domain topology is highly conserved, and all subunits are present or lost together, showing that the complexes are ancient and functionally interdependent. Finally, each subfamily has a distinctive C motif, indicating that this motif plays a specific role in each subfamily's function, unlike the generic V and A motifs. Our analysis identifies which features are universally conserved, and thus essential, and which are branch-specific modifications. It also shows the WASP family is more widespread and diverse than currently appreciated and unexpectedly biases the physiological role of the Arp2/3 complex toward vesicle traffic. PMID- 20573980 TI - Overlapping roles of Drosophila Drak and Rok kinases in epithelial tissue morphogenesis. AB - Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence suggests that other mechanisms must be involved. Here, we report the identification of a single Drosophila homologue of the Death-associated protein kinase (DAPK) family, called Drak, as a regulator of MRLC phosphorylation. Based on analysis of null mutants, we find that Drak broadly promotes proper morphogenesis of epithelial tissues during development. Drak activity is largely redundant with that of the Drosophila ROCK orthologue, Rok, such that it is essential only when Rok levels are reduced. We demonstrate that these two kinases synergistically promote phosphorylation of Spaghetti squash (Sqh), the Drosophila MRLC orthologue, in vivo. The lethality of drak/rok mutants can be rescued by restoring Sqh activity, indicating that Sqh is the critical common effector of these two kinases. These results provide the first evidence that DAPK family kinases regulate actin dynamics in vivo and identify Drak as a novel component of the signaling networks that shape epithelial tissues. PMID- 20573981 TI - Transgene rescue identifies an essential function for Drosophila beta spectrin in the nervous system and a selective requirement for ankyrin-2-binding activity. AB - The protein spectrin is ubiquitous in animal cells and is believed to play important roles in cell shape and membrane stability, cell polarity, and endomembrane traffic. Experiments here were undertaken to identify sites of essential beta spectrin function in Drosophila and to determine whether spectrin and ankyrin function are strictly linked to one another. The Gal4-UAS system was used to drive tissue-specific overexpression of a beta spectrin transgene or to knock down beta spectrin expression with dsRNA. The results show that 1) overexpression of beta spectrin in most of the cell types studied was lethal; 2) knockdown of beta spectrin in most tissues had no detectable effect on growth or viability of the organism; and 3) nervous system-specific expression of a UAS beta spectrin transgene was sufficient to overcome the lethality of a loss-of function beta spectrin mutation. Thus beta spectrin expression in other cells was not required for development of fertile adult males, although females lacking nonneuronal spectrin were sterile. Previous data indicated that binding of the DAnk1 isoform of ankyrin to spectrin was partially dispensable for viability. Domain swap experiments here uncovered a different requirement for neuronal DAnk2 binding to spectrin and establish that DAnk2-binding is critical for beta spectrin function in vivo. PMID- 20573982 TI - Sequential counteracting kinases restrict an asymmetric gene expression program to early G1. AB - Gene expression is restricted to specific times in cell division and differentiation through close control of both activation and inactivation of transcription. In budding yeast, strict spatiotemporal regulation of the transcription factor Ace2 ensures that it acts only once in a cell's lifetime: at the M-to-G1 transition in newborn daughter cells. The Ndr/LATS family kinase Cbk1, functioning in a system similar to metazoan hippo signaling pathways, activates Ace2 and drives its accumulation in daughter cell nuclei, but the mechanism of this transcription factor's inactivation is unknown. We found that Ace2's nuclear localization is maintained by continuous Cbk1 activity and that inhibition of the kinase leads to immediate loss of phosphorylation and export to the cytoplasm. Once exported, Ace2 cannot re-enter nuclei for the remainder of the cell cycle. Two separate mechanisms enforce Ace2's cytoplasmic sequestration: 1) phosphorylation of CDK consensus sites in Ace2 by the G1 CDKs Pho85 and Cdc28/CDK1 and 2) an unknown mechanism mediated by Pho85 that is independent of its kinase activity. Direct phosphorylation of CDK consensus sites is not necessary for Ace2's cytoplasmic retention, indicating that these mechanisms function redundantly. Overall, these findings show how sequential opposing kinases limit a daughter cell specific transcriptional program to a brief period during the cell cycle and suggest that CDKs may function as cytoplasmic sequestration factors. PMID- 20573983 TI - EHBP-1 functions with RAB-10 during endocytic recycling in Caenorhabditis elegans. AB - Caenorhabditis elegans RAB-10 functions in endocytic recycling in polarized cells, regulating basolateral cargo transport in the intestinal epithelia and postsynaptic cargo transport in interneurons. A similar role was found for mammalian Rab10 in MDCK cells, suggesting that a conserved mechanism regulates these related pathways in metazoans. In a yeast two-hybrid screen for binding partners of RAB-10 we identified EHBP-1, a calponin homology domain (CH) protein, whose mammalian homolog Ehbp1 was previously shown to function during endocytic transport of GLUT4 in adipocytes. In vivo we find that EHBP-1-GFP colocalizes with RFP-RAB-10 on endosomal structures of the intestine and interneurons and that ehbp-1 loss-of-function mutants share with rab-10 mutants specific endosome morphology and cargo localization defects. We also show that loss of EHBP-1 disrupts transport of membrane proteins to the plasma membrane of the nonpolarized germline cells, a defect that can be phenocopied by codepletion of RAB-10 and its closest paralog RAB-8. These results indicate that RAB-10 and EHBP 1 function together in many cell types and suggests that there are differences in the level of redundancy among Rab family members in polarized versus nonpolarized cells. PMID- 20573984 TI - Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271. AB - CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related kinases. Here we found that homeodomain-interacting protein kinase 2 (HIPK2), a DNA-damage responsive nuclear kinase, is a new CREB kinase for phosphorylation at Ser-271 but not Ser-133, and activates CREB transactivation function including brain derived neurotrophic factor (BDNF) mRNA expression. Ser-271 to Glu-271 substitution potentiated the CREB transactivation function. ChIP assays in SH SY5Y neuroblastoma cells demonstrated that CREB Ser-271 phosphorylation by HIPK2 increased recruitment of a transcriptional coactivator CBP (CREB binding protein) without modulation of CREB binding to the BDNF CRE sequence. HIPK2-/- MEF cells were more susceptible to apoptosis induced by etoposide, a DNA-damaging agent, than HIPK2+/+ cells. Etoposide activated CRE-dependent transcription in HIPK2+/+ MEF cells but not in HIPK2-/- cells. HIPK2 knockdown in SH-SY5Y cells decreased etoposide-induced BDNF mRNA expression. These results demonstrate that HIPK2 is a new CREB kinase that regulates CREB-dependent transcription in genotoxic stress. PMID- 20573985 TI - The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression. AB - Nuclear export of mRNA is an essential process for eukaryotic gene expression. The TREX complex couples gene expression from transcription and splicing to mRNA export. Sub2, a core component of the TREX complex in yeast, has diversified in humans to two closely related RNA helicases, UAP56 and URH49. Here, we show that URH49 forms a novel URH49-CIP29 complex, termed the AREX (alternative mRNA export) complex, whereas UAP56 forms the human TREX complex. The mRNAs regulated by these helicases are different at the genome-wide level. The two sets of target mRNAs contain distinct subsets of key mitotic regulators. Consistent with their target mRNAs, depletion of UAP56 causes mitotic delay and sister chromatid cohesion defects, whereas depletion of URH49 causes chromosome arm resolution defects and failure of cytokinesis. In addition, depletion of the other human TREX components or CIP29 causes mitotic defects similar to those observed in UAP56- or URH49-depleted cells, respectively. Taken together, the two closely related RNA helicases have evolved to form distinct mRNA export machineries, which regulate mitosis at different steps. PMID- 20573986 TI - Differential proteomics analysis reveals a role for E2F2 in the regulation of the Ahr pathway in T lymphocytes. AB - E2F transcription factors (E2F1-8) are best known for their role in cell proliferation, although it is clear that they regulate many other biological processes through the transcriptional modulation of distinct target genes. However, the specific set of genes regulated by each E2F remains to be characterized. To gain insight into the molecular pathways regulated by E2F2, we have analyzed the proteome of antigen receptor-activated T cells lacking E2F2. We report that loss of E2F2 results in a deregulated Aryl-hydrocarbon-receptor pathway. Proliferating E2F2(-/-) T lymphocytes expressed significantly higher levels of Aip, Ahr, and Arnt relative to wild-type (WT)(1) controls. The mechanism for increased levels of Aip appears straightforward, involving direct regulation of the Aip gene promoter by E2F2. Although the Ahr and Arnt promoters also bind E2F2, their regulation appears to be more complex. Nevertheless, exposure to the environmental xenobiotic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a well-known exogenous ligand of the Ahr pathway, led to overexpression of the Ahr target gene Cyp1a1, and to increased sensitivity to TCDD-triggered apoptosis in E2F2(-/-) T cells compared with WT controls. These results suggest that E2F2 modulates cellular sensitivity to xenobiotic signals through the negative regulation of the Ahr pathway. PMID- 20573987 TI - Sex differences in acute ANG II-mediated hemodynamic responses in mice. AB - Male sex is associated with higher blood pressure and greater renal injury, perhaps related to greater sensitivity to ANG II. In anesthetized male and female C57BLK/6 mice, we assessed responses of mean arterial pressure (MAP) and renal vascular resistance (RVR; Transonic flow probe) to acute bolus injections of ANG II (0.3-3.0 microg/kg iv) and phenylephrine (PE; 30-300 microg/kg) during low-, normal-, and high-sodium diets. The role of reactive oxygen species was determined by coadministration of tempol. ANG II type 1 and type 2 (AT1 and AT2) receptor and endothelial nitric oxide synthase (NOS3) expression were determined in dissected kidney vessels. While no difference was found on the low-sodium (LS) diet, MAP and RVR responses to ANG II were greater in males during the normal sodium (NS) and high-sodium (HS) diets (e.g., RVR response at ANG II 3.0 microg/kg during NS: +329 +/- 22 vs. +271 +/- 28 mmHg.ml(-1).min, P = 0.029, effect size = 0.75). Tempol had no effect on the sex-dependent responses on any of the diets. On the LS diet, AT1 and AT2 receptor expression was higher in males. No sex differences were found on the NS diet. On the HS diet, AT1 was higher, and NOS3 expression was lower in males. Acute responses to ANG II are greater in male mice during NS and HS diets, which is, in part, related to differences in AT1, AT2, and NOS3 expression in kidney vessels. Mouse models will be useful to study the role of sex differences in ANG II sensitivity for cardiovascular and renal disease. PMID- 20573988 TI - Thujone, a component of medicinal herbs, rescues palmitate-induced insulin resistance in skeletal muscle. AB - Thujone is thought to be the main constituent of medicinal herbs that have antidiabetic properties. Therefore, we examined whether thujone ameliorated palmitate-induced insulin resistance in skeletal muscle. Soleus muscles were incubated for < or =12 h without or with palmitate (2 mM). Thujone (0.01 mg/ml), in the presence of palmitate, was provided in the last 6 h of incubation. Palmitate oxidation, AMPK/acetyl-CoA carboxylase (ACC) phosphorylation and insulin-stimulated glucose transport, plasmalemmal GLUT4, and AS160 phosphorylation were examined at 0, 6, and 12 h. Palmitate treatment for 12 h reduced fatty acid oxidation (-47%), and insulin-stimulated glucose transport ( 71%), GLUT4 translocation (-40%), and AS160 phosphorylation (-26%), but it increased AMPK (+51%) and ACC phosphorylations (+44%). Thujone (6-12 h) fully rescued palmitate oxidation and insulin-stimulated glucose transport, but only partially restored GLUT4 translocation and AS160 phosphorylation, raising the possibility that an increased GLUT4 intrinsic activity may also have contributed to the restoration of glucose transport. Thujone also further increased AMPK phosphorylation but had no further effect on ACC phosphorylation. Inhibition of AMPK phosphorylation with adenine 9-beta-d-arabinofuranoside (Ara) (2.5 mM) or compound C (50 muM) inhibited the thujone-induced improvement in insulin stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation. In contrast, the thujone-induced improvement in palmitate oxidation was only slightly inhibited (< or =20%) by Ara or compound C. Thus, while thujone, a medicinal herb component, rescues palmitate-induced insulin resistance in muscle, the improvement in fatty acid oxidation cannot account for this thujone-mediated effect. Instead, the rescue of palmitate-induced insulin resistance appears to occur via an AMPK-dependent mechanism involving partial restoration of insulin stimulated GLUT4 translocation. PMID- 20573989 TI - Nerve-released acetylcholine contracts urinary bladder smooth muscle by inducing action potentials independently of IP3-mediated calcium release. AB - Nerve-released ACh is the main stimulus for contraction of urinary bladder smooth muscle (UBSM). Here, the mechanisms by which ACh contracts UBSM are explored by determining Ca(2+) and electrical signals induced by nerve-released ACh. Photolysis of caged inositol 1,4,5-trisphosphate (IP(3)) evoked Ca(2+) release from the sarcoplasmic reticulum. Electrical field stimulation (20 Hz) induced Ca(2+) waves within the smooth muscle that were present only during stimulus application. Ca(2+) waves were blocked by inhibition of muscarinic ACh receptors (mAChRs) with atropine and depletion of sarcoplasmic reticulum Ca(2+) stores with cyclopiazonic acid (CPA), and therefore likely reflect activation of IP(3) receptors (IP(3)Rs). Electrical field stimulation also increased excitability to induce action potentials (APs) that were accompanied by Ca(2+) flashes, reflecting Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) during the action potential. The evoked Ca(2+) flashes and APs occurred as a burst with a lag time of approximately 1.5 s after onset of stimulation. They were not inhibited by blocking IP(3)-mediated Ca(2+) waves, but by blockers of mAChRs (atropine) and VDCCs (diltiazem). Nerve-evoked contractions of UBSM strips were greatly reduced by blocking VDCCs, but not by preventing IP(3)-mediated Ca(2+) signaling with cyclopiazonic acid or inhibition of PLC with U73122. These results indicate that ACh released from nerve varicosities induces IP(3)-mediated Ca(2+) waves during stimulation; but contrary to expectations, these signals do not appear to participate in contraction. In addition, our data provide compelling evidence that UBSM contractions evoked by nerve-released ACh depend on increased excitability and the resultant Ca(2+) entry through VDCCs during APs. PMID- 20573990 TI - Race, sex, and the regulation of urine osmolality: observations made during water deprivation. AB - A more concentrated urine is excreted by blacks than whites and by men than women. The purpose of this study was to explore the physiological bases for the race and sex effects during water deprivation when osmoregulation is challenged and differences are amplified. Drinking water was withheld from 17 blacks (10 men) and 19 whites (9 men) for 24 h. Vasopressin (VP) levels and osmolality in plasma (P(osmol)) and urine (U(osmol)) were measured basally and then every 4 h. U(osmol) was higher in blacks at baseline (P = 0.01) and during water deprivation (P = 0.046). Before and during water deprivation, no differences were seen in levels of VP, P(osmol), or the VP-U(osmol) relationship between blacks and whites. Although VP levels were initially higher in men (P < 0.02 for samples collected over the first 12 h), over the last 12 h of water deprivation, U(osmol) was higher (P = 0.027) and more responsive to the level of VP (in terms of slopes, P = 0.0001) in women than men. Our results suggest that, after a period of water deprivation, there develops a sensitivity of the collecting duct to VP that is greater in women. Although U(osmol) is higher in blacks, the race difference in water conservation did not appear to result from differences in the level of VP or the sensitivity of the collecting duct to VP. Upstream effects such as Na(+) uptake in the thick ascending limb, with its ensuing effects on water reabsorption, need to be considered in future studies of the relationship of race to water conservation. PMID- 20573991 TI - Disparate effects of feeding on core body and adipose tissue temperatures in animals selectively bred for Nervous or Calm temperament. AB - In addition to homeostatic regulation of body mass, nonhomeostatic factors impact on energy balance. Herein we describe effects of temperament on adipose and core body temperatures in sheep. Animals were genetically selected for Nervous or Calm traits. We characterized the effects of 1) high- and low-energy intake and maintenance feeding, 2) meal anticipation, and 3) adrenocorticotropin challenge on core body and adipose temperatures. Temperature measurements (5 min) were made using a thermistor inserted into the carotid artery (core body) and a probe in the retroperitoneal fat. An imposed feeding window was used to establish postprandial elevations in temperature. Fat tissue was taken from retroperitoneal and subcutaneous regions for real-time PCR analyses. We demonstrate that innate differences in temperament impact on adipose and core body temperatures in response to various dietary and evocative stimuli. In response to homeostatic cues (low-energy intake and maintenance feeding) core body temperature tended to be higher in Calm compared with Nervous animals. In contrast, in response to nonhomeostatic cues, Nervous animals had higher anticipatory thermogenic responses than Calm animals. Expression of uncoupling protein (UCP)-1 and -2 mRNA were higher in retroperitoneal tissue than in subcutaneous tissue, but UCP3 and leptin mRNA levels were similar at both sites; expression of these genes was similar in Nervous and Calm animals. There were no differences in stress responsiveness. We conclude that temperament differentially influences adipose thermogenesis and the regulation of core body temperature in responses to both homeostatic and nonhomeostatic stimuli. PMID- 20573992 TI - Regulation of circulating progenitor cells in left ventricular dysfunction. AB - BACKGROUND: Reductions in numbers of circulating progenitor cells (CD34+ cell subsets) have been demonstrated in patients at risk for, or in the presence of, cardiovascular disease. The mediators of these reductions remain undefined. To determine whether neurohumoral factors might regulate circulating CD34+ cell subsets in vivo, we studied complementary canine models of left ventricular (LV) dysfunction. METHODS AND RESULTS: A pacing model of severe LV dysfunction and a hypertensive renal wrap model in which dogs were randomized to receive deoxycorticosterone acetate (DOCA) were studied. Circulating CD34+ cell subsets including hematopoietic precursor cells (HPCs: CD34+/CD45(dim)/VEGFR2-) and endothelial progenitor cells (EPCs: CD34+/CD45-/VEGFR2+) were quantified. Additionally, the effect of mineralocorticoid excess on circulating progenitor cells in normal dogs was studied. The majority of circulating CD34+ cells expressed CD45dimly and did not express VEGFR2, consistent with an HPC phenotype. HPCs were decreased in response to pacing, and this decrease correlated with plasma aldosterone levels (Spearman rank correlation=-0.67, P=0.03). In the hypertensive renal wrap model, administration of DOCA resulted in decreased HPCs. No changes were seen in EPCs in either model. Normal dogs treated with DOCA exhibited a decrease in HPCs in peripheral blood but not bone marrow associated with decreased telomerase activity. CONCLUSIONS: This is the first study to demonstrate that mineralocorticoid excess, either endogenous or exogenous, results in reduction in HPCs. These data suggest that mineralocorticoids may induce accelerated senescence of progenitor cells, leading to their reduced survival and decline in numbers. PMID- 20573993 TI - BNP levels predict outcome in pediatric heart failure patients: post hoc analysis of the Pediatric Carvedilol Trial. AB - BACKGROUND: The ability of serum B-type natriuretic peptide levels (BNP) to predict outcomes in children with heart failure (HF) has not been well demonstrated. This study was designed to determine whether BNP levels predict outcomes in patients with moderate symptomatic HF. METHODS AND RESULTS: We investigated whether enrollment BNP levels for the Pediatric Carvedilol Trial were associated with baseline characteristics. Freedom from a composite end point of HF hospitalization, death, or transplantation at 9 months was compared using a threshold BNP level identified using receiver operating curve analysis. Median BNP level was 110 pg/mL (interquartile range, 22.4 to 342.0 pg/mL) in 138 subjects. Median age was 3.4 years (interquartile range, 1.1 to 11.0 years). Diagnoses were cardiomyopathy (60%) and congenital heart disease (40%); 73% had a systemic left ventricle. BNP levels correlated moderately with left ventricular ejection fraction (R=0.39, P<0.001) but did not differ by HF class, age, diagnosis, sex, ventricular morphology, or left ventricular end-diastolic dimension Z-score (R=0.19). Outcome events included 25 HF hospitalizations, 4 deaths, and 2 transplants. Sensitivity was 71% and specificity 63%, for a BNP cutoff value of 140 pg/mL. BNP >=140 pg/mL (hazard ratio, 3.7; 95% confidence interval, 1.62 to 8.4; P=0.002) and age >2 years (hazard ratio, 4.45; 95% confidence interval, 1.68 to 12.04; P=0.003) were independently associated with worse outcomes. CONCLUSIONS: In children with moderately symptomatic HF, BNP >=140 pg/mL and age >2 years identified subjects at higher risk for worse outcome. Further validation is needed to determine the BNP levels necessary to stratify risk in other pediatric cohorts. PMID- 20573994 TI - Positive and negative cis-regulatory elements directing postfertilization maternal mRNA translational control in mouse embryos. AB - Mechanisms providing for temporally complex patterns of maternal mRNA translation after fertilization are poorly understood. We employed bioinformatics analysis to compare populations of mRNAs enriched specifically on polysomes at the metaphase II (MII) stage oocyte and late one-cell stages and a detailed deletion/truncation series to identify elements that regulate translation. We used the Bag4 3' untranslated region (UTR) as a model. Bioinformatics analysis revealed one conserved motif, subsequently confirmed by functional studies to be a key translation repressor element. The deletion/truncation studies revealed additional regulatory motifs, most notably a strong translation activator element of <30 nt. Analysis of mRNA secondary structure suggests that secondary structure plays a key role in translation repression. Additional bioinformatics analysis of the regulated mRNA population revealed a diverse collection of regulatory motifs found in small numbers of mRNAs, highlighting a high degree of sequence diversity and combinatorial complexity in the overall control of the maternal mRNA population. We conclude that translational control after fertilization is driven primarily by negative regulatory mechanisms opposing strong translational activators, with stage-specific release of the inhibitory influences to permit recruitment. The combination of bioinformatics analysis and deletion/truncation studies provides the necessary approach for dissecting postfertilization translation regulatory mechanisms. PMID- 20573995 TI - RNA interference screen for RGS protein specificity at muscarinic and protease activated receptors reveals bidirectional modulation of signaling. AB - Regulator of G protein signaling (RGS) proteins are considered key modulators of G protein-coupled receptor (GPCR)-mediated signal transduction. These proteins act directly on Galpha subunits in vitro to increase their intrinsic rate of GTP hydrolysis; this activity is central to the prevailing view of RGS proteins as negative regulators of agonist-initiated GPCR signaling. However, the specificities of action of particular RGS proteins toward specific GPCRs in an integrated cellular context remain unclear. Here, we developed a medium throughput assay to address this question in a wholly endogenous context using RNA interference. We performed medium-throughput calcium mobilization assays of agonist-stimulated muscarinic acetylcholine and protease-activated receptors in human embryonic kidney 293 (HEK293) cells transfected with individual members of a "pooled duplex" short interfering RNA library targeting all conventional human RGS transcripts. Only knockdown of RGS11 increased both carbachol-mediated calcium mobilization and inositol phosphate accumulation. Surprisingly, we found that knockdown of RGS8 and RGS9, but not other conventional RGS proteins, significantly decreased carbachol-mediated calcium mobilization, whereas only RGS8 knockdown decreased protease-activated receptor-1 (PAR-1)-mediated calcium mobilization. Loss of responsiveness toward carbachol and PAR-1 agonist peptide upon RGS8 knockdown appears due, at least in part, to a loss in respective receptor cell surface expression, although this is not the case for RGS9 knockdown. Our data suggest a cellular role for RGS8 in the stable surface expression of M3 muscarinic acetylcholine receptor and PAR-1, as well as a specific and opposing set of functions for RGS9 and RGS11 in modulating carbachol responsiveness similar to that seen in Caenorhabditis elegans. PMID- 20573996 TI - Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. AB - Hyperglycemia is an indication of poor outcome for heart attack patients, even for nondiabetic patients with stress-induced hyperglycemia. Previous studies showed that inhibition of aldose reductase, the first and rate-limiting enzyme of the polyol pathway, attenuated contractile dysfunction in diabetic animals, but the mechanism is unclear. We therefore wanted to find out whether the polyol pathway also contributes to acute hyperglycemia-induced cardiac contractile dysfunction, and determine the mechanism involved. Rat hearts were isolated and retrogradely perfused with Krebs buffer containing either normal or high concentrations of glucose for 2 h. Short exposure to high-glucose medium led to contractile dysfunction as indicated by decreased -dP/dt(max), as well as elevation in left ventricular end-diastolic pressure. Cardiomyocytes incubated in high-glucose medium showed abnormal Ca2+ signaling, most likely because of decreased activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inactivated by oxidative stress. Inhibition of aldose reductase or sorbitol dehydrogenase, the second enzyme in the polyol pathway, ameliorated contractile dysfunction, attenuated oxidative stress, and normalized Ca2+ signaling and SERCA activity caused by high glucose, indicating that the polyol pathway is the major contributor to acute hyperglycemia-induced oxidative stress leading to the inactivation of SERCA and contractile dysfunction. PMID- 20573998 TI - A novel role for sphingolipid metabolism in oxidant-mediated skeletal muscle fatigue. Focus on "Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue". PMID- 20573997 TI - Lipopolysaccharides directly decrease Ca2+ oscillations and the hyperpolarization activated nonselective cation current If in immortalized HL-1 cardiomyocytes. AB - Lipopolysaccharide (LPS) has been implicated in sepsis-mediated heart failure and chronic cardiac myopathies. We determined that LPS directly and reversibly affects cardiac myocyte function by altering regulation of intracellular Ca2+ concentration ([Ca2+]i) in immortalized cardiomyocytes, HL-1 cells. [Ca2+]i oscillated (<0.4 Hz), displaying slow and transient components. LPS (1 microg/ml), derived either from Escherichia coli or from Salmonella enteritidis, reversibly abolished Ca2+ oscillations and decreased basal [Ca2+]i by 30-40 nM. HL-1 cells expressed Toll-like receptors, i.e., TLR-2 and TLR-4. Thus, we differentiated effects of LPS on [Ca2+]i and Ca2+ oscillations by addition of utlrapure LPS, a TLR-4 ligand. Ultrapure LPS had no effect on basal [Ca2+]i, but it reduced the rate of Ca2+ oscillations. Interestingly, Pam3CSK4, a TLR-2 ligand, affected neither Ca2+ parameter, and the effect of ultrapure LPS and Pam3CSK4 combined was similar to that of utlrapure LPS alone. Thus, unpurified LPS directly inhibits HL-1 calcium metabolism via TLR-4 and non-TLR-4-dependent mechanisms. Since others have shown that endotoxin impairs the hyperpolarization activated, nonselective cationic pacemaker current (I(f)), which is expressed in HL-1 cells, we utilized whole cell voltage-clamp techniques to demonstrate that LPS (1 microg/ml) reduced I(f) in HL-1 cells. This inhibition was marginal at physiologic membrane potentials and significant at very negative potentials (P < 0.05 at -140, -150, and -160 mV). So, we also evaluated effects of LPS on tail currents of fully activated I(f). LPS reduced the slope conductance of the tail currents from 498 +/- 140 pS/pF to 223 +/- 65 pS/pF (P < 0.05) without affecting reversal potential of -11 mV. Ultrapure LPS had similar effect on I(f), whereas Pam3CSK4 had no effect on I(f). We conclude that LPS inhibits activation of I(f), enhances its deactivation, and impairs regulation of [Ca2+]i in HL-1 cardiomyocytes via TLR-4 and other mechanisms. PMID- 20573999 TI - Perceptions of coronary heart disease risk in African American women with type 2 diabetes: a qualitative study. AB - PURPOSE: The purpose of this study was to explore the perceptions of coronary heart disease (CHD) risk in a group of southern African American women with type 2 diabetes (T2DM). METHODS: Semistructured interviews were conducted in participants' homes or setting of choice. The interviews were conducted with 6 participants from a larger study of 48 women who were stratified into levels of low, medium, and high perception of CHD risk, with 2 participants in each group. The interviews were analyzed using NVivo software; both investigators recoded and analyzed the data. RESULTS: African American women with T2DM do not believe they are at risk for CHD unless they are told specifically by their primary health care provider that they have heart disease. The African American women in the study expressed that managing their diabetes to prevent heart disease can be overwhelming. Participants identified faith beliefs called not claiming the illness as a reason they did not perceive themselves at risk for CHD. CONCLUSIONS: Not claiming an illness may influence health and preventive behaviors. Many African American women with T2DM may not claim their illness. Diabetes educators should acknowledge and address women's beliefs to create an appropriate plan of care. PMID- 20574001 TI - Acute hypoxia induces HIF-independent monocyte adhesion to endothelial cells through increased intercellular adhesion molecule-1 expression: the role of hypoxic inhibition of prolyl hydroxylase activity for the induction of NF-kappa B. AB - Myeloid cells recruited to sites of bacterial inflammation are exposed to low oxygen tension, hypoxia, and high concentrations of inflammatory cytokines that significantly affect myeloid cell function. Therefore, we analyzed the direct consequences of acute and severe hypoxia on monocytic adhesion to the endothelium in coculture experiments. Marked upregulation of monocytic ICAM-1, but no other monocytic adhesion molecule, was responsible for an approximately 50-fold increase in adhesion of the monocytic cells THP-1 to human and rat endothelial cells. ICAM-1 expression was rapidly induced after the onset of severe hypoxia, but it decreased after 4 h. Knockdown of ICAM-1 by siRNA in endothelial and monocytic cells abolished the adhesion, indicating that ICAM-1 expression on both cell types was indispensable for hypoxia-induced adhesion of monocytes to the endothelium. siRNA-mediated knockdown of hypoxia inducible factor (HIF)-1alpha, HIF-2alpha, and the NF-kappaB family member p65 revealed that hypoxic upregulation of ICAM-1 resulted from hypoxic NF-kappaB induction but not from activation of HIFs. Within the leukocyte-adhesion cascade, our results provide evidence for prolyl hydroxylase-dependent but HIF-independent activation of hypoxia-induced monocyte-endothelial adhesion and assign a new function to monocytic ICAM-1 under acute hypoxic conditions. PMID- 20574000 TI - GPR17 regulates immune pulmonary inflammation induced by house dust mites. AB - Antagonists of the type 1 cysteinyl leukotriene receptor (CysLT(1)R) are efficacious for bronchoconstriction in humans with bronchial asthma; however, the clinical response to these drugs is heterogeneous. In particular, how CysLT(1)R expression and function are constitutively regulated in vivo is not known. In this study, we show that a seven-transmembrane receptor, GPR17, negatively regulates the CysLT(1)R-mediated inflammatory cell accumulation in the bronchoalveolar lavage fluid and lung, the levels of IgE and specific IgG1 in serum, and Th2/Th17 cytokine expression in the lung after intranasal sensitization and challenge with the house dust mite (extract of Dermatophagoides farinae [Df]) in mice. Sensitization of naive wild-type recipients with Df-pulsed bone marrow-derived dendritic cells of each genotype or sensitization of each genotype with Df-pulsed wild-type bone marrow-derived dendritic cells and Df challenge revealed markedly increased pulmonary inflammatory and serum IgE responses for GPR17-deficient mice as compared with wild-type mice and reduced responses in the genotypes lacking CysLT(1)R. These findings reveal a constitutive negative regulation of CysLT(1)R functions by GPR17 in both the Ag presentation and downstream phases of allergic pulmonary inflammation. PMID- 20574002 TI - Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft versus-host disease. AB - We previously showed that transplantation with IL-21R gene-deficient splenocytes resulted in less severe graft-versus-host disease (GVHD) than was observed with wild type splenocytes. In this study, we sought to find mechanism(s) explaining this observation. Recipients of donor CD4(+) T cells lacking IL-21R exhibited diminished GVHD symptoms, with reduced inflammatory cell infiltration into the liver and intestine, leading to prolonged survival. After transplantation, CD4(+) T cell numbers in the spleen were reduced, and MLR and cytokine production by CD4(+) T cells were impaired. These results suggest that IL-21 might promote GVHD through enhanced production of effector CD4(+) T cells. Moreover, we found that CD25 depletion altered neither the impaired MLR in vitro nor the ameliorated GVHD symptoms in vivo. Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells. PMID- 20574003 TI - CXCL13 blockade disrupts B lymphocyte organization in tertiary lymphoid structures without altering B cell receptor bias or preventing diabetes in nonobese diabetic mice. AB - Lymphocytes that invade nonlymphoid tissues often organize into follicle-like structures known as tertiary lymphoid organs (TLOs). These structures resemble those found in spleen or lymph nodes, but their function is unknown. TLOs are recognized in many autoimmune diseases, including the NOD mouse model of type 1 diabetes. In some cases, TLOs have been associated with the B lymphocyte chemoattractant, CXCL13. Studies presented in this article show that CXCL13 is present in inflamed islets of NOD mice. Ab blockade of this chemokine unraveled B lymphocyte organization in islet TLOs, without reducing their proportion in the islets. These chaotic milieus contained B lymphocytes with the same distinct repertoire of B cell receptors as those found in mice with well-organized structures. Somatic hypermutation, associated with T-B interactions, was not impaired in these disorganized insulitis lesions. Finally, loss of B lymphocyte organization in islets did not provide disease protection. Thus, B lymphocytes infiltrating islets in NOD mice do not require the morphology of secondary lymphoid tissues to support their role in disease. PMID- 20574005 TI - Critical role for TNF in the induction of human antigen-specific regulatory T cells by tolerogenic dendritic cells. AB - TNF is a pleiotropic cytokine with differential effects on immune cells and diseases. Anti-TNF therapy was shown to be effective in rheumatoid arthritis but proved inefficient or even detrimental in other autoimmune diseases. We studied the role of TNF in the induction of Ag-specific regulatory T cells (Tregs) by tolerogenic vitamin D3-modulated human dendritic cells (VD3-DCs), which previously were shown to release high amounts of soluble TNF (sTNF) upon maturation with LPS. First, production of TNF by modulated VD3-DCs was analyzed upon maturation with LPS or CD40L with respect to both secreted (cleaved) TNF (sTNF) and expression of the membrane-bound (uncleaved) form of TNF (mTNF). Next, TNF antagonists were tested for their effect on induction of Ag-specific Tregs by modulated DCs and the subsequent functionality of these Tregs. VD3-DCs expressed greater amounts of mTNF than did control DCs (nontreated DCs), independent of the maturation protocol. Inhibition of TNF with anti-TNF Ab (blocking both sTNF and mTNF) during the priming of Tregs with VD3-DCs prevented generation of Tregs and their suppression of proliferation of CD4(+) T cells. In contrast, sTNF receptor II (sTNFRII), mainly blocking sTNF, did not change the suppressive capacity of Tregs. Blocking of TNFRII by anti-CD120b Ab during Treg induction similarly abrogated their subsequent suppressive function. These data point to a specific role for mTNF on VD3-DCs in the induction of Ag-specific Tregs. Interaction between mTNF and TNFRII instructs the induction of suppressive Tregs by VD3-DCs. Anti-TNF therapy may therefore act adversely in different patients or disease pathways. PMID- 20574004 TI - NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. AB - The interplay between innate and adaptive immunity is important in multiple sclerosis (MS). The inflammasome complex, which activates caspase-1 to process pro-IL-1beta and pro-IL-18, is rapidly emerging as a pivotal regulator of innate immunity, with nucleotide-binding domain, leucine-rich repeat containing protein family, pyrin domain containing 3 (NLRP3) (cryopyrin or NALP3) as a prominent player. Although the role of NLRP3 in host response to pathogen associated molecular patterns and danger associated molecular patterns is well documented, its role in autoimmune diseases is less well studied. To investigate the role of NLRP3 protein in MS, we used a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Nlrp3 expression was elevated in the spinal cords during EAE, and Nlrp3(-/-) mice had a dramatically delayed course and reduced severity of disease. This was accompanied by a significant reduction of the inflammatory infiltrate including macrophages, dendritic cells, CD4, and CD8(+) T cells in the spinal cords of the Nlrp3(-/-) mice, whereas microglial accumulation remained the same. Nlrp3(-/-) mice also displayed improved histology in the spinal cords with reduced destruction of myelin and astrogliosis. Nlrp3(-/-) mice with EAE produced less IL-18, and the disease course was similar to Il18(-/-) mice. Furthermore, Nlrp3(-/-) and Il18(-/-) mice had similarly reduced IFN-gamma and IL-17 production. Thus, NLRP3 plays a critical role in the induction of the EAE, likely through effects on capase-1-dependent cytokines which then influence Th1 and Th17. PMID- 20574006 TI - Distal regions of the human IFNG locus direct cell type-specific expression. AB - Genes, such as IFNG, which are expressed in multiple cell lineages of the immune system, may employ a common set of regulatory elements to direct transcription in multiple cell types or individual regulatory elements to direct expression in individual cell lineages. By employing a bacterial artificial chromosome transgenic system, we demonstrate that IFNG employs unique regulatory elements to achieve lineage-specific transcriptional control. Specifically, a one 1-kb element 30 kb upstream of IFNG activates transcription in T cells and NKT cells but not in NK cells. This distal regulatory element is a Runx3 binding site in Th1 cells and is needed for RNA polymerase II recruitment to IFNG, but it is not absolutely required for histone acetylation of the IFNG locus. These results support a model whereby IFNG uses cis-regulatory elements with cell type restricted function. PMID- 20574007 TI - Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. AB - IFN-gamma plays a central role in antitumor immunity. T cell Ig and mucin domain (Tim-3) is expressed on IFN-gamma-producing Th1 cells; on interaction with its ligand, galectin-9, Th1 immunity is terminated. In this study, we show that transgenic overexpression of Tim-3 on T cells results in an increase in CD11b(+)Ly-6G(+) cells and inhibition of immune responses. Molecular characterization of CD11b(+)Ly-6G(+) cells reveals a phenotype consistent with granulocytic myeloid-derived suppressor cells. Accordingly, we find that modulation of the Tim-3/galectin-9 (Gal-9) pathway impacts on tumor growth. Similarly, overexpression of Tim-3 ligand, Gal-9, results in an increase in CD11b(+)Ly-6G(+) cells and inhibition of immune responses. Loss of Tim-3 restores normal levels of CD11b(+)Ly-6G(+) cells and normal immune responses in Gal-9 transgenic mice. Our data uncover a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses and identifies this pathway as a therapeutic target in diseases where myeloid-derived suppressor cells are disadvantageous. PMID- 20574008 TI - sRAGE induces human monocyte survival and differentiation. AB - The receptor for advanced glycation end products (RAGE) is produced either as a transmembrane or soluble form (sRAGE). Substantial evidence supports a role for RAGE and its ligands in disease. sRAGE is reported to be a competitive, negative regulator of membrane RAGE activation, inhibiting ligand binding. However, some reports indicate that sRAGE is associated with inflammatory disease. We sought to define the biological function of sRAGE on inflammatory cell recruitment, survival, and differentiation in vivo and in vitro. To test the in vivo impact of sRAGE, the recombinant protein was intratracheally administered to mice, which demonstrated monocyte- and neutrophil-mediated lung inflammation. We also observed that sRAGE induced human monocyte and neutrophil migration in vitro. Human monocytes treated with sRAGE produced proinflammatory cytokines and chemokines. Our data demonstrated that sRAGE directly bound human monocytes and monocyte-derived macrophages. Binding of sRAGE to monocytes promoted their survival and differentiation to macrophages. Furthermore, sRAGE binding to cells increased during maturation, which was similar in freshly isolated mouse monocytes compared with mature tissue macrophages. Because sRAGE activated cell survival and differentiation, we examined intracellular pathways that were activated by sRAGE. In primary human monocytes and macrophages, sRAGE treatment activated Akt, Erk, and NF-kappaB, and their activation appeared to be critical for cell survival and differentiation. Our data suggest a novel role for sRAGE in monocyte- and neutrophil-mediated inflammation and mononuclear phagocyte survival and differentiation. PMID- 20574009 TI - Corneal hysteresis and visual field asymmetry in open angle glaucoma. AB - PURPOSE: To investigate the association between corneal biomechanical parameters and asymmetric primary open angle glaucoma (POAG) using the Ocular Response Analyzer (ORA). METHODS: In a prospective cross-sectional study, ORA parameters were measured in 117 POAG patients with asymmetric visual fields (VF). The asymmetry in VF was defined as a five point difference between the eyes using the Advanced Glaucoma Intervention Study (AGIS) scoring system. Subjects with previous intraocular or refractive surgery, ocular comorbidities and diabetes were excluded. RESULTS: In worse eyes, mean AGIS scores were significantly higher (8.1 +/- 4.3 vs. 1.0 +/- 1.6; P < 0.001) and mean corneal hysteresis (CH) was significantly lower (8.2 +/- 1.9 vs. 8.9 +/- 1.9 mm Hg; P < 0.001). Median ORA corrected intraocular pressure was higher in the worse eyes (IOP(cc), 17.4 mm Hg vs. 16.9 mm Hg; P < 0.001). Worse eyes had a slightly lower mean corneal resistance factor (P = 0.04) and more myopic mean spherical equivalent (P = 0.02). No difference was seen in the central corneal thickness (CCT; P = 0.63) and Goldmann applanation tonometry (GAT; P = 0.32). On multivariate analysis, only CH retained an association with the worse eye (odds ratio, 25.9; 95% confidence interval, 10.1-66.5). ROC curves showed that only CH and IOP(cc) had a discriminative ability for the eye with worse VF (AUC, 0.82 and 0.70, respectively). CONCLUSIONS: Asymmetric POAG was associated with asymmetry in ORA parameters but not in CCT and GAT. Lower CH was associated with worse eyes independently of its effect on IOP measurement and had the best discriminability for the eye with the worse VF. PMID- 20574011 TI - Comparison of multiple stereoscopic and monoscopic digital image formats to film for diabetic macular edema evaluation. AB - PURPOSE: To assess agreement between evaluations of monoscopic and stereoscopic digital images versus stereo film photographs in diabetic macular edema (DME). METHODS: A 152-eye group of digital monoscopic macular images (seven-field sets and wide-angle mosaics) were compared with digital stereoscopic images (uncompressed and compressed seven-field sets) and stereo 35-mm film photos (Early Treatment Diabetic Retinopathy Study protocol) for the presence of hard exudates (HE), retinal thickening (RT), clinically significant macular edema (CSME), and RT at the center of the macular (RTCM). RESULTS: Agreement, according to the kappa statistic, was almost perfect in identifying HE and RT between all digital formats and stereo film (HE, kappa = 0.81-0.87; RT, kappa = 0.87-0.92). Distribution in all digital formats was not significantly different from that in film (Bhapkar test: HE, P = 0.20-0.40; RT, P = 0.06-1.0). CSME and RTCM grading differences were either significant or trended toward significance. The readers detected CSME and RTCM in film images more often than in digital formats. In identifying DME features, agreement between evaluations of monoscopic digital formats and film was similar to that between stereo digital formats and film, and the performance of uncompressed images versus film was similar to that of compressed images versus film. Repeatability between readers was similar in evaluations of film and all digital formats. Repeatability in identifying RTCM was lower than that of other DME components in film and all digital formats. CONCLUSIONS: Stereoscopic digital formats are equivalent to monoscopic for DME evaluation, but digital photography is not as sensitive as film in detecting CSME and RTCM. PMID- 20574012 TI - Poly(I:C)-induced adhesion molecule expression mediated by NF-{kappa}B and phosphoinositide 3-kinase-Akt signaling pathways in human corneal fibroblasts. AB - PURPOSE: Viral infection at the ocular surface can lead to the chronic condition of viral stromal keratitis. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, induces the expression of adhesion molecules in cultured corneal fibroblasts. The authors investigated the roles of nuclear factor (NF)-kappaB and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways in the poly(I:C)-induced expression of adhesion molecules in corneal fibroblasts. METHODS: Human corneal fibroblasts were cultured with poly(I:C) in the absence or presence of IkappaB kinase 2 (IKK2) inhibitor (an inhibitor of NF-kappaB activation) or the PI3K inhibitor LY294002. The expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, ICAM-2, and E-selectin, as well as the phosphorylation of the NF-kappaB inhibitory protein IkappaB-alpha and Akt, were examined by immunoblot analysis. The subcellular localization of adhesion molecules was determined by immunofluorescence analysis. RESULTS: Poly(I:C) increased the expression of VCAM-1 and ICAM-1 but not that of ICAM-2 or E-selectin in corneal fibroblasts. Poly(I:C) also induced the phosphorylation of IkappaB-alpha and Akt. The poly(I:C)-induced expression of VCAM-1 and ICAM-1 was attenuated by both IKK2 inhibitor and LY294002. CONCLUSIONS: The NF-kappaB and PI3K-Akt signaling pathways mediate the poly(I:C) induced upregulation of VCAM-1 and ICAM-1 in corneal fibroblasts, with PI3K acting upstream of NF-kappaB activation. These pathways thus likely modulate local immune and inflammatory responses to viral infection in the corneal stroma. PMID- 20574010 TI - Intralysosomal iron induces lysosomal membrane permeabilization and cathepsin D mediated cell death in trabecular meshwork cells exposed to oxidative stress. AB - PURPOSE: To investigate the role of intralysosomal redox-active iron in oxidative stress-induced damage in trabecular meshwork (TM) cells. METHODS: Chronic oxidative stress was applied using the hyperoxic model; acute oxidative stress was applied with H(2)O(2). Microarray analysis was performed using microarrays. mRNA and protein levels were quantified by real-time PCR and Western blot analysis, respectively. Redox-active iron was monitored using calcein-AM. Apoptosis was quantified using double staining. DNA damage was evaluated by single-cell gel electrophoresis assay. Lysosomal permeabilization was monitored using uptake and acridine orange relocation techniques. Intracellular ROS production was quantified using H(2)DCFDA. Cytosolic translocation of cathepsins was visualized with pepstatin-A-BODIPY-FL. Chemical inhibition of cathepsins was achieved with leupeptin and pepstatin A. Silencing of cathepsin expression was accomplished with miRNA sequences. Lysosomal iron chelation was achieved with desferrioxamine. RESULTS: Chronically stressed TM cells showed elevated levels of redox-active iron and altered expression of genes involved in intracellular iron homeostasis. Although iron increased ROS production and lipofuscin levels and sensitized TM cells to H(2)O(2), intralysosomal iron chelation completely protected the cells against H(2)O(2)-induced cell death and apoptosis. The protective effect of desferrioxamine was mediated by the prevention of lysosomal ROS generation and the rupture of lysosomal membrane, with the subsequent release of cathepsin D into the cytosol. CONCLUSIONS: These results indicate that the generation of intralysosomal ROS induces lysosomal membrane permeabilization and the release of cathepsin D into the cytosol, leading to TM cell death. Here, the authors propose a mechanism by which oxidative stress might contribute to the decrease in cellularity reported in the TM tissue with both aging and disease. PMID- 20574013 TI - CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. AB - PURPOSE: To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). METHODS: The three polymorphisms were genotyped in a case-control study of 1351 control subjects and 962 patients with AMD. RESULTS: The three polymorphisms correlated with AMD (Y402H, P = 1.54 * 10(-6); I62V, P =1.94 * 10(-29); and A69S, P = 9.56 * 10(-43)). The I62V and A69S polymorphisms were associated with all three subtypes: tAMD (P = 3.74 * 10(-18) and 1.37 * 10(-35), respectively), PCV (P = 3.18 * 10(-19) and 3.96 * 10(-18), respectively), and RAP (P = 0.034 and 2.49 * 10(-18), respectively). Y402H was associated with tAMD (P = 3.00 * 10(-5)) and with PCV (P = 9.73 * 10(-5)), but no association was found with RAP, possibly because of the small sample size and the rare minor allele. The risk allele contribution of A69S was stronger for RAP than for tAMD or PCV and was stronger for tAMD than for PCV. CONCLUSIONS: CFH Y402H is associated with AMD, tAMD, and PCV, whereas I62V is associated with all three subtypes. ARMS2 A69S has a strong association with all three subtypes, with the association being strongest for RAP and weakest for PCV. PCV and RAP may thus be subtypes of AMD that are genetically distinct from tAMD. PMID- 20574014 TI - Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. AB - PURPOSE: To assess the reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured with Cirrus HD OCT in glaucomatous eyes. METHODS: Fifty-five glaucomatous eyes were included in the study. The optic disc cube 200 * 200 protocol was used to obtain three scans during the same visit to evaluate the intravisit reproducibility. One scan on 4 additional days within a 2-month period of the first session was obtained to assess intervisit reproducibility. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and test-retest SD (TRT SD) were calculated for each RNFL and ONH parameter. The formula 1.645 * ?2 * intervisit TRT SD provides an upper tolerance limit to variability beyond which nonphysiologic change should be considered. RESULTS: All ICCs were excellent, ranging from 83.9% to 99.2% for intravisit measurements and from 80.8% to 99.1% for intervisit measurements. Cup/disc area ratio had the lowest CV (1.1%) in either type of measurement, followed by average RNFL thickness (1.9% and 2.7%). Nasal clock hours and quadrants showed the poorest reproducibility as did the clock hour directly temporally. The intervisit tolerance limit for average RNFL thickness was 3.89 MUm. CONCLUSIONS: Intravisit and intervisit measurements of peripapillary RNFL thickness and ONH parameters with Cirrus HD-OCT showed excellent reproducibility, indicating that this instrument may be useful in monitoring glaucoma progression. When comparing two measurements from the same eye on two different visits, a reproducible decrease in average RNFL thickness of approximately 4 MUm or more may be considered a statistically significant change from baseline. PMID- 20574015 TI - Circadian variations in intracranial pressure and translaminar pressure difference in Sprague-Dawley rats. AB - PURPOSE: To study the circadian (24-hour) change in intracranial pressure (ICP) in conscious, freely moving rats and to project the circadian change in translaminar pressure difference. METHODS: Telemetric pressure transmitters were implanted to monitor ICP in the lateral ventricle in nine light-dark-entrained Sprague-Dawley rats. ICP and locomotor activity data were collected. The mean results for the 12-hour light period and the 12-hour dark period were compared. The light-dark change in ICP was also determined in six rats under an acute 24 hour constant dark condition. The circadian translaminar pressure difference was projected based on the ICP data and the previously established circadian pattern of intraocular pressure (IOP). RESULTS: Under the standard light-dark condition, the hourly average ICP was relatively constant (7.47-10.90 mm Hg). The light-dark ICP difference was -0.11 +/- 1.45 mm Hg (mean +/- SD, P = 0.823), whereas the locomotor activity was significantly higher during the dark period (P < 0.01). Under the acute constant dark condition, the subjective light-dark ICP difference remained small. Compared with a significant light-dark IOP elevation of 5.15 +/- 4.47 mm Hg (P = 0.037) in rats housed under the same laboratory conditions, the light-dark ICP variation was considered minimal. The translaminar pressure difference was projected to be 5.26 mm Hg higher in the dark period (mean, 17.10 mm Hg) than in the light period (mean 11.84 mm Hg). CONCLUSIONS: There is no significant circadian ICP variation in Sprague-Dawley rats. The translaminar pressure difference is projected to be higher during the dark period because of the change in IOP. PMID- 20574016 TI - Antifibrotic activity of bevacizumab on human Tenon's fibroblasts in vitro. AB - PURPOSE: To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenon's capsule fibroblasts (HTFs) in an in vitro model of wound healing. METHODS: Fibroblasts were cultured in RPMI media, and bevacizumab was administered at a concentration ranging from 0.25 to 12.5 mg/mL. Fibroblast viability and cell death were assessed using the MTT colorimetric assay, lactate dehydrogenase assay, BrdU assay, and live/dead assay. Fibroblast contractility was assessed in floating collagen gels. Morphologic changes were assessed by transmission electron microscopy. Antifibrosis activities were compared with 5-fluorouracil. RESULTS: Bevacizumab induced a significant dose related reduction of HTF cell number at 12.5 mg/mL at 72 hours (P < 0.05). Under serum-free conditions, bevacizumab induced significant fibroblast cell death at concentrations greater than 7.5 mg/mL (P < 0.05). Bevacizumab caused a moderate inhibition of fibroblast gel contraction from baseline (P < 0.05). Scanning electron microscopy revealed marked vacuolization in bevacizumab-treated fibroblasts. CONCLUSIONS: Bevacizumab disrupted fibroblast proliferation, inhibited collagen gel contraction ability, and induced fibroblast cell death at concentrations greater than 7.5 mg/mL in serum-free conditions. These results demonstrated that bevacizumab inhibited a number of fibrosis activities in culture. These activities may underpin the antifibrosis effect proposed in vivo. PMID- 20574017 TI - Effect of chondroitin sulfate on intraocular pressure in rats. AB - PURPOSE: To study the effect of intracameral injections of chondroitin sulfate (CS) on intraocular pressure (IOP), retinal function, and histology in rats. METHODS: Acute or chronic injections of CS were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with vehicle. IOP was daily or weekly assessed by a tonometer. Retinal function was assessed by scotopic electroretinography (ERG) and the visual pathway by flash visual evoked potentials (VEPs), whereas the retinal and optic nerve head structure were examined by histologic analysis. RESULTS: A single injection of 8 mg (but not 2 or 4 mg) CS induced a significant increase of IOP. The increase of IOP induced by a single injection of 8 mg CS lasted for 7 days, whereas chronic (weekly) administration during 10 weeks induced a significant and sustained increase in IOP compared with eyes injected with vehicle. A significant decrease of scotopic ERG a- and b- wave amplitude was observed after 6 and 10 weeks of CS administration. Moreover, a significant decrease in scotopic flash VEP N2-P2 component amplitude was observed in eyes treated with CS for 6 and 10 weeks. A significant loss of ganglion cell layer cells and optic nerve axons was observed in eyes receiving CS for 10 weeks. CONCLUSIONS: These results suggest that exogenous CS simulates the accumulation of CS in primary open-angle glaucoma and that increased amounts of CS could play a key role in the IOP dysregulation characteristic of glaucoma. PMID- 20574018 TI - Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. AB - PURPOSE: To investigate the safety and preliminary efficacy of OT-551, a disubstituted hydroxylamine with antioxidant properties, for the treatment of geographic atrophy (GA), the advanced atrophic form of age-related macular degeneration (AMD). METHODS: The study was a single-center, open-label phase II trial, enrolling 10 participants with bilateral GA. Topical 0.45% OT-551 was administered in one randomly assigned eye three times daily for 2 years. Safety measures were assessed by complete ophthalmic examination, fundus photography, and review of symptoms. The primary efficacy outcome measure was the change in best corrected visual acuity at 24 months. Secondary efficacy measures included changes in area of GA, contrast sensitivity, microperimetry measurements, and total drusen area from baseline. RESULTS: Study drug was well tolerated and was associated with few adverse events. The mean change in BCVA at 2 years was +0.2 +/- 13.3 letters in the study eyes and -11.3 +/- 7.6 letters in fellow eyes (P = 0.0259). However, no statistically significant differences were found between the study and fellow eyes for all other secondary outcome measures. CONCLUSIONS: OT 551 was well tolerated by study participants and was not associated with any serious adverse effects. Efficacy measurements in this small study indicate a possible effect in maintaining visual acuity. However, the absence of significant effects on other outcomes measures in this study suggests that OT-551, in the current concentration and mode of delivery, may have limited or no benefit as a treatment for GA (ClinicalTrials.gov number, NCT00306488). PMID- 20574019 TI - Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration. AB - PURPOSE: To observe detailed changes in neurosensory retinal structure after anti VEGF upload in age-related macular degeneration (AMD), by using spectral domain optical coherence tomography (SD-OCT). METHODS: The retinal structure was observed by using SD-OCT in 61 patients, before and 1 month after the third ranibizumab injection (upload phase). The main focus of attention was a subjective determination of the amount and behavior of the numerous small, dense particles (SDPs) frequently observed within the outer and inner neurosensory layers in eyes with neovascular AMD. The Spearman rho correlation was used for statistical analysis. RESULTS: In all eyes, various amounts of SDPs were seen within the neurosensory layer of the foveal and parafoveal area. In 54%, the amount of SDPs became significantly less after ranibizumab therapy (stable, 41%; higher, 5%). SDP reduction correlated positively with the reduction of retinal disease according to OCT (P = 0.000), with central foveal thickness (P = 0.040), and with the improvement in best corrected visual acuity (BCVA; P = 0.006). The baseline amount of SDPs also correlated positively with the increase in BCVA (P = 0.005). CONCLUSIONS: The origin of the SDPs observable in SD-OCT is unknown, but they may represent migrating RPE cells or leukocytes, indicating a certain status of retinal inflammation. The amount of SDPs is substantially reduced after ranibizumab upload therapy and correlates positively with BCVA. Moreover, an initial large number of SDPs may indicate a higher grade of inflammation, but the presence of a high number enhances the effect of ranibizumab therapy. Thus, the amount of SDPs before treatment may be a predictive factor for the therapy's outcome. PMID- 20574021 TI - Association of glutathione S-transferases polymorphisms (GSTM1 and GSTT1) with senile cataract: a meta-analysis. AB - PURPOSE: Glutathione S-transferase (GST) polymorphisms have been considered risk factors for the development of senile cataract. However, the results are not consistent. In this study, the authors conducted a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for senile cataract. METHODS: Published literature from PubMed, EMBASE, and other databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and senile cataract were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. RESULTS: Eleven studies on GSTM1 (1871 cases and 1267 controls) and five studies on GSTT1 (1180 cases, 706 controls) were included. Overall analysis showed that the association between GSTM1 null genotype and risk for senile cataract is not statistically significant (OR, 1.39; 95% CI, 0.99-1.94; P = 0.054) and that the association between GSTT1 null genotype and risk for senile cataract is not significant (OR, 1.09; 95% CI, 0.87-1.36; P = 0.454). Subgroup analysis showed that the association between GSTM1 null genotype and risk for senile cataract is statistically significant in Asians (OR, 1.66; 95% CI, 1.03-2.67; P = 0.039) but not in Caucasians (OR, 1.21; 95% CI, 0.74-1.96; P = 0.443). Similar results were observed for the association between GSTT1 null genotype and risk for senile cataract. CONCLUSIONS: The present meta-analysis suggested that GSTM1 and GSTT1 null genotypes are associated with increased risk for senile cataract in Asian populations but not in Caucasian populations. Given the limited sample size, the finding on GST polymorphisms merits further investigation. PMID- 20574020 TI - In glaucoma the upregulated truncated TrkC.T1 receptor isoform in glia causes increased TNF-alpha production, leading to retinal ganglion cell death. AB - PURPOSE: Glaucoma is a distinct neuropathy characterized by the chronic and progressive death of retinal ganglion cells (RGCs). The etiology of RGC death remains unknown. Risk factors for glaucomatous RGC death are elevated intraocular pressure and glial production of tumor necrosis factor-alpha (TNF-alpha). Previously, the authors showed that glaucoma causes a rapid upregulation of a neurotrophin receptor truncated isoform lacking the kinase domain, TrkC.T1, in retina. Here they examined the biological role of TrkC.T1 during glaucoma progression. METHODS: Rat and mouse models of chronic ocular hypertension were used. Immunofluorescence Western blot analysis and in situ mRNA hybridization were used to identify cells upregulating TrkC.T1. A genetic model of engineered mice lacking TrkC.T1 (TrkC.T1(-/-)) was used to validate a role for this receptor in glaucoma. Pharmacologic studies were conducted to evaluate intravitreal delivery of agonists or antagonists of TrkC.T1, compared with controls, during glaucoma. Surviving RGCs were quantified by retrograde-labeling techniques. Production of neurotoxic TNF-alpha and alpha2 macroglobulin were quantified. RESULTS: TrkC.T1 was upregulated in retinal glia, with a pattern similar to that of TNF-alpha. TrkC.T1(-/-) mice had normal retinas. However, during experimental glaucoma, TrkC.T1(-/-) mice had lower rates of RGC death and produced less TNF alpha than wild-type littermates. In rats with glaucoma, the pharmacologic use of TrkC antagonists delayed RGC death and reduced the production of retinal TNF alpha. CONCLUSIONS: TrkC.T1 is implicated in glaucomatous RGC death through the control of glial TNF-alpha production. Overall, the data point to a paracrine mechanism whereby elevated intraocular pressure upregulated glial TrkC.T1 expression in glia; TrkC.T1 controlled glial TNF-alpha production, and TNF-alpha caused RGC death. PMID- 20574022 TI - Reproducibility of spectral-domain optical coherence tomography total retinal thickness measurements in mice. AB - PURPOSE: To test the reproducibility of spectral-domain optical coherence tomography (SD-OCT) total retinal thickness (TRT) measurements in mice. METHODS: C57Bl/6 mice were anesthetized, and three repeated volumetric images were acquired in both eyes with SD-OCT (250 A-scans * 250 frames * 1024 samplings), centered on the optic nerve head (ONH). The mice were repositioned between scans. TRT was automatically measured within a sampling band of retinal thickness with radii of 55 to 70 pixels, centered on the ONH by using custom segmentation software. The first volumetric image acquired in a given eye was used to register the remaining two SD-OCT images by manually aligning the en face images with respect to rotation and linear translation. Linear mixed-effects models were fitted to global and quadrant thicknesses, taking into account the clustering between eyes, to assess imprecision (measurement reproducibility). RESULTS: Twenty-six eyes of 13 adult mice (age 13 weeks) were imaged. The mean global TRT across all eyes was 298.21 MUm, with a mouse heterogeneity standard deviation (SD) of 4.88 MUm (coefficient of variation [CV] = 0.016), an eye SD of 3.32 MUm (CV = 0.011), and a device-related imprecision SD of 2.33 MUm (CV = 0.008). The superior quadrant had the thickest mean TRT measurement (310.38 MUm) and the highest (worst) imprecision SD (3.13 MUm; CV = 0.010), and the inferior quadrant had the thinnest mean TRT (291.55 MUm). The quadrant with the lowest (best) imprecision SD was in the nasal one (2.06 MUm; CV = 0.007). CONCLUSIONS: Good reproducibility was observed for SD-OCT retinal thickness measurements in mice. SD-OCT may be useful for in vivo longitudinal studies in mice. PMID- 20574023 TI - Effective and sustained delivery of hydrophobic retinoids to photoreceptors. AB - PURPOSE: Delivery of hydrophobic compounds to the retina/RPE has been challenging. The purpose of this study was to develop an effective method for the sustained delivery of retinoids to rod and cone photoreceptors of young mice lacking a normal supply of 11-cis retinal. METHODS: Solubilized basement membrane matrix (Matrigel; BD Biosciences, San Jose, CA) loaded with 9-cis retinal was administered subcutaneously into Rpe65(-/-) mouse pups for assessment of delivery to rods and cones and to Rpe65(-/-)Rho(-/-) mouse pups for assessment of delivery to cones. Intraperitoneal injections of 9-cis retinal were used for comparison. Cone density and opsin localization were evaluated with immunohistochemistry. Cone opsin protein levels were assayed with immunoblots, and cone function was analyzed by electroretinography (ERG) recordings. Retinoid content was determined by high-performance liquid chromatography analysis of retinal extracts. Pigment levels were quantified in homogenized retinas by absorption spectroscopy before and after light exposure. RESULTS: Single administration of Matrigel loaded with 9-cis retinal to Rpe65(-/-) mice increased cone densities in all analyzed regions of the retina compared with mice treated using intraperitoneal delivery. Cone opsin levels increased to near wild-type levels. Similar treatment in Rpe65(-/ )Rho(-/-) mice increased b-wave ERG amplitudes significantly, indicating the maintenance of cone function. Matrigel was shown to continuously release 9-cis retinal for periods up to 1 week. CONCLUSIONS: As a method for sustained drug delivery, subcutaneous administration using Matrigel proved more efficacious than intraperitoneal injection for in vivo delivery of retinoids to cone photoreceptors. These experiments are the first to show a sustained delivery of retinoids in mice and suggest a strategy for potential clinical therapeutic development. PMID- 20574024 TI - Twist2: role in corneal stromal keratocyte proliferation and corneal thickness. AB - PURPOSE: Twist2 is a member of a family of bHLH transcription factors critical for normal mesenchymal proliferation and differentiation. In this study, the authors analyzed the role of Twist2 in the eye and cornea through examination of a Twist2 loss-of-function mouse mutant. METHODS: Twist2 expression during eye development in the mouse was investigated using RT-PCR and mRNA slide in situ hybridization. Lineage tracing was performed using Cre reporter mice. Morphometric analyses were performed, and cell proliferation and cell death were investigated by immunohistochemistry using Ki67 and cleaved caspase 3 antibodies, respectively. RESULTS: In the mouse, Twist2 is expressed first in the periocular mesenchyme and subsequently in the corneal stroma and endothelium of the developing eye. Loss of Twist2 function leads to corneal thinning and a reduced population of stromal keratocytes. The reduction in the stromal cell population can be traced back to embryonic stages during which the proliferation of stromal progenitor cells is impaired and to the reduced number of proliferating cells in the corneal limbus postnatally. Adult Twist2-null mice display enophthalmia and blepharophimosis. Corneal thinning in mutant mice is not accompanied by glaucoma, an association reported in human patients. CONCLUSIONS: Twist2 is required for normal corneal keratocyte proliferation and eyelid morphogenesis in the mouse. Loss of Twist2 function leads to corneal thinning because of the reduction in stromal keratocyte proliferation. PMID- 20574025 TI - Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk. AB - PURPOSE: Anophthalmos, microphthalmos, and typical coloboma (AMC) form an interrelated spectrum of congenital eye anomalies that can cause significant visual loss and cosmetic disfigurement in children. This prospective study of children born in the United Kingdom was undertaken to determine the incidence of AMC diagnosed by ophthalmologists and to explore sociodemographic risks. METHODS: Recruitment was achieved though an established active surveillance system of U.K. ophthalmologists supported by a new research network of interested specialists, the Surveillance of Eye Anomalies (SEA-UK) Special Interest Group. It started October 1, 2006, and continued over 18 months. RESULTS: One hundred thirty-five children were newly diagnosed with AMC. Typical colobomatous defects were the commonest phenotype, and anophthalmos was rare (n = 7). Both eyes were affected in 55.5% of the children. The cumulative incidence of AMC by age 16 years was 11.9 per 100,000 (95% CI, 10.9-15.4). Of the children examined, 41.5% had not seen an ophthalmologist by 3 months of age. The incidence in Scotland was nearly double that in England and Wales. The children of Pakistani ethnicity had a 3.7 (95% CI, 1.9-7.5) times higher risk of AMC than did white children. There was some evidence to suggest a higher incidence in the more socioeconomically deprived. The sibling risk ratio was 210 (95% CI, 25-722). CONCLUSIONS: This is the first prospective study of AMC, and it establishes the frequency across the United Kingdom. Comparisons with data quoted in the literature are difficult because study methodologies differ, but the frequency appears to be lower than that quoted for other developed countries. There are geographic and ethnic variations in incidence that warrant further investigation. PMID- 20574026 TI - Increased hyaluronan synthase-2 mRNA expression and hyaluronan accumulation with choroidal thickening: response during recovery from induced myopia. AB - PURPOSE: Several studies have convincingly shown that in chicks, compensation for imposed focus involves immediate changes in choroid thickness. The molecular events associated with choroidal thickening and the regulation of the choroidal response are largely unknown. METHODS: Form-deprivation myopia was induced in the right eyes of 2-day-old chicks by the application of translucent occluders for 10 days and was followed by unrestricted vision for an additional 1 to 20 days (recovery). Individual choroids were isolated from treated and control eyes and used for reverse transcription-quantitative PCR, hyaluronan (HA) localization with biotinylated hyaluronic acid binding protein (b-HABP), and analyses of HA size and concentration by size exclusion chromatography-multiangle laser light scattering (SEC-MALLS). RESULTS: HAS2 gene expression increased significantly after 6 hours of unrestricted vision (>7-fold) and peaked at 24 hours (>9-fold). In untreated eyes, HA was localized to perivascular sheaths of larger choroidal blood vessels; however, after 4 to 15 days of recovery, intense labeling for HA was detected throughout the thickened choroidal stroma. Analyses of choroidal HA by SEC-MALLS indicated that HA concentration was significantly increased in recovering choroids compared with controls after 4 to 8 days of recovery (~3.5 fold). CONCLUSIONS: Newly synthesized HA accumulates in the choroidal stroma of recovering eyes and is most likely responsible for the stromal swelling observed during recovery from myopia. This HA accumulation is initiated by a rapid increase in choroidal expression of the HAS2 gene in response to myopic defocus. PMID- 20574027 TI - The respective relationships between lipoprotein profile, macular pigment optical density, and serum concentrations of lutein and zeaxanthin. AB - PURPOSE: The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported on lipoproteins in the serum. The mechanism of delivery of L and Z to the macula, where they constitute macular pigment (MP), is poorly understood. This study was an investigation of the respective relationships between serum lipoprotein profile, MP optical density (MPOD), and serum L and Z. METHODS: Three hundred two healthy subjects were recruited; 211 (69.9%) were women. Demographic and health details were recorded. Fasting blood samples were taken for lipoprotein analysis by spectrophotometric assay and L and Z analysis by high-performance liquid chromatography. MPOD was measured by heterochromatic flicker photometry. RESULTS: The mean +/- SD (range) age of all subjects was 48 +/- 11 (21-66) years. There was a statistically significant and positive association between serum L concentration and both serum cholesterol concentration (r = 0.239, P < 0.001) and serum HDL concentration (r = 0.324, P < 0.001), but not with serum LDL concentration (r = 0.095, P = 0.101). There was a statistically significant but inverse association between serum triglyceride concentration and total MPOD (r = 0.118, P = 0.044). There was no significant association between MPOD and serum cholesterol concentration or serum HDL concentration (P > 0.05). CONCLUSIONS: The findings are consistent with the hypothesis that HDL is important for the transport of L in serum. The mechanism(s) whereby L and Z are captured by the macula and whether the serum (apo)lipoprotein profile is important in the transfer of the carotenoids from serum to retina merit further study. PMID- 20574028 TI - Changes of osteopontin in the aqueous humor of the DBA2/J glaucoma model correlated with optic nerve and RGC degenerations. AB - PURPOSE: To identify age-dependent regulated aqueous humor (AH) factors in DBA2/J (D2J) mice and to correlate them with optic nerve degeneration and intraocular pressure (IOP) by population and individual analysis. METHODS: AH samples of D2J mice aged 2 (n = 3), 7 (n = 5), and 10 months (n = 14) were analyzed by mouse cytokine antibody array. Ten-month samples were classified into eyes with (D2J+) or without (D2J-) optic neuropathy. Ten-month-old C57/Bl6 (B6; n = 13) and DBA2/Rj (D2Rj; n = 15) mice served as controls. IOP was recorded from 2 to 10 months. Individual AH osteopontin (OPN) was determined in 31 D2J eyes (10 months) and was correlated with optic neuropathy and IOP. OPN mRNA was detected by in situ hybridization. OPN blood plasma content of D2J and B6 was monitored from 8 to 10 months. Effect of OPN on cell survival in the ganglion cell layer (GCL) or metabolism was tested in ex vivo-cultured D2Rj eyes and murine neuronal precursors. RESULTS: In array analysis, OPN was detected in 10-month-old D2J mice only. They significantly differed between D2J- and D2J+ (P = 0.006). By Western blot analysis, a sevenfold OPN increase in D2J+ was determined compared with B6. Individual analysis confirmed the positive correlation of OPN with optic neuropathy. IOP was not correlated with OPN. OPN blood plasma contents steadily increased with age in D2J. OPN(+) cells were detected within the ciliary body of D2J, and OPN(+) RGCs were ~30% reduced. OPN treatment inhibited cell degeneration within the GCL in ex vivo-cultured D2Rj eyes and increased the metabolic activity of neuronal precursor cells. CONCLUSIONS: OPN is an age-dependent increased AH factor associated with degeneration of the optic nerve in D2J mice. By modulating the metabolism of neuronal cells, deregulated levels of OPN could be involved in degenerative processes affecting RGCs or optic nerve axons in the D2J model. PMID- 20574029 TI - Progressive loss of cones in achromatopsia: an imaging study using spectral domain optical coherence tomography. AB - PURPOSE: Achromatopsia (ACHM) is a congenital autosomal recessive cone disorder with a presumed stationary nature and only a few causative genes. Animal studies suggest that ACHM may be a good candidate for corrective gene therapy. Future implementation of this therapy in humans requires the presence of viable cone cells in the retina. In this study the presence of cone cells in ACHM was determined, as a function of age. METHODS: The appearance and thickness of all retinal layers were evaluated by spectral-domain optical coherence tomography (SD OCT) in 40 ACHM patients (age range, 4-70 years) with known mutations in the CNGB3, CNGA3, and PDE6C genes. A comparison was made with 55 healthy age-matched control subjects. RESULTS: The initial feature of cone cell decay was loss of inner and outer segments with disruption of the ciliary layer on OCT, which was observed as early as 8 years of age. Cone cell loss further progressed with age and occurred in 8 (42%) of 19 patients below 30 years and in 20 (95%) of 21 of those aged 30+ years. Retinal thickness was significantly thinner in the fovea of all patients (126 MUm in ACHM vs. 225 MUm in the control; P < 0.001) and correlated with age (beta = 0.065; P = 0.011). Foveal hypoplasia was present in 24 (80%) of 30 patients and in 1 of 55 control subjects. CONCLUSIONS: ACHM is not a stationary disease. The first signs of cone cell loss occur in early childhood. If intervention becomes available in the future, the present results imply that it should be applied in the first decade. PMID- 20574031 TI - Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells. AB - PURPOSE: To characterize and investigate the mechanism of chloroquine (CQ) retinotoxicity in human retinal pigment epithelium-derived ARPE-19 cells. METHODS: Cultured ARPE-19 cells were exposed to 10 to 250 MUM CQ, and cell death was quantified using a lactate dehydrogenase release assay. Autophagy was studied in ARPE-19 cells transfected with GFP-LC3. Lysosomes in living cells were stained and observed by live-cell confocal microscopy. RESULTS: After exposure to CQ, ARPE-19 cells developed cytosolic vacuoles within 1 hour and underwent cell lysis within 24 hours. The levels of LC3-II, beclin-1 and, p62, as well as the number GFP-LC3- and RPF-LC3-positive autophagic vacuoles (AVs), increased after CQ treatment, indicating that autophagy was activated. However, lysosomal staining revealed that almost all AVs were separate from lysosomes; thus, fusion between AVs and lysosomes was completely blocked. In addition, the levels of ubiquitinated proteins and GFP-mHttp aggregates in ARPE-19 cells were increased by CQ, providing further evidence that autophagic degradation was inhibited. CONCLUSIONS: CQ induces vacuole formation and cell death in ARPE-19 cells. Initially, vacuoles developed from enlarged lysosomes, followed by the activation of upstream steps in the autophagy pathway and the formation of LC3-positive AVs. Because CQ blocked the fusion of AVs with lysosomes, autophagic protein degradation was inhibited, indicating that CQ-induced retinotoxicity may be caused by the accumulation of potentially toxic ubiquitinated proteins. PMID- 20574030 TI - Transcriptional profile analysis of RPGRORF15 frameshift mutation identifies novel genes associated with retinal degeneration. AB - PURPOSE: To identify genes and molecular mechanisms associated with photoreceptor degeneration in a canine model of XLRP caused by an RPGR exon ORF15 microdeletion. Methods. Expression profiles of mutant and normal retinas were compared by using canine retinal custom cDNA microarrays. qRT-PCR, Western blot analysis, and immunohistochemistry (IHC) were applied to selected genes, to confirm and expand the microarray results. RESULTS: At 7 and 16 weeks, respectively, 56 and 18 transcripts were downregulated in the mutant retinas, but none were differentially expressed (DE) at both ages, suggesting the involvement of temporally distinct pathways. Downregulated genes included the known retina relevant genes PAX6, CHML, and RDH11 at 7 weeks and CRX and SAG at 16 weeks. Genes directly or indirectly active in apoptotic processes were altered at 7 weeks (CAMK2G, NTRK2, PRKCB, RALA, RBBP6, RNF41, SMYD3, SPP1, and TUBB2C) and 16 weeks (SLC25A5 and NKAP). Furthermore, the DE genes at 7 weeks (ELOVL6, GLOD4, NDUFS4, and REEP1) and 16 weeks (SLC25A5 and TARS2) are related to mitochondrial functions. qRT-PCR of 18 genes confirmed the microarray results and showed DE of additional genes not on the array. Only GFAP was DE at 3 weeks of age. Western blot and IHC analyses also confirmed the high reliability of the transcriptomic data. CONCLUSIONS: Several DE genes were identified in mutant retinas. At 7 weeks, a combination of nonclassic anti- and proapoptosis genes appear to be involved in photoreceptor degeneration, whereas at both 7 and 16 weeks, the expression of mitochondria-related genes indicates that they may play a relevant role in the disease process. PMID- 20574032 TI - GLUT1-ous maximus epilepticus: the expanding phenotype of GLUT-1 mutations and epilepsy. PMID- 20574033 TI - Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. AB - BACKGROUND: Familial glucose transporter type 1 (GLUT1) deficiency due to autosomal dominant inheritance of SLC2A1 mutations is associated with paroxysmal exertional dyskinesia; epilepsy and intellectual disability occur in some family members. We recently demonstrated that GLUT1 deficiency occurs in over 10% of patients with early-onset absence epilepsy. METHODS: This family study analyses the phenotypes in 2 kindreds segregating SLC2A1 mutations identified through probands with early-onset absence epilepsy. One comprised 9 individuals with mutations over 3 generations; the other had 6 individuals over 2 generations. RESULTS: Of 15 subjects with SLC2A1 mutations, epilepsy occurred in 12. Absence seizures were the most prevalent seizure type (10/12), with onset from 3 to 34 years of age. Epilepsy phenotypes varied widely, including idiopathic generalized epilepsies (IGE) with absence (8/12), myoclonic-astatic epilepsy (2/12), and focal epilepsy (2/12). Paroxysmal exertional dyskinesia occurred in 7, and was subtle and universally undiagnosed prior to molecular diagnosis. There were 2 unaffected mutation carriers. CONCLUSIONS: GLUT1 deficiency is an important monogenic cause of absence epilepsies with onset from early childhood to adult life. Individual cases may be phenotypically indistinguishable from common forms of IGE. Although subtle paroxysmal exertional dyskinesia is a helpful diagnostic clue, it is far from universal. The phenotypic spectrum of GLUT1 deficiency is considerably greater than previously recognized. Diagnosis of GLUT1 deficiency has important treatment and genetic counseling implications. PMID- 20574034 TI - Quality of life declines after first ischemic stroke. The Northern Manhattan Study. AB - OBJECTIVES: Quality of life (QOL) after stroke is poorly characterized. We sought to determine long-term natural history and predictors of QOL among first ischemic stroke survivors without stroke recurrence or myocardial infarction (MI). METHODS: In the population-based, multiethnic Northern Manhattan Study, QOL was prospectively assessed at 6 months and annually for 5 years using the Spitzer QOL index (QLI), a 10-point scale. Functional status was assessed using the Barthel Index (BI) at regular intervals, and cognition using the Mini-Mental State Examination at 1 year. Generalized estimating equations estimated the association between patient characteristics and repeated QOL measures over 5 years. Follow-up was censored at death, recurrent stroke, or MI. RESULTS: There were 525 incident ischemic stroke patients >/=40 years (mean age 68.6 +/- 12.4 years). QLI declined after stroke (annual change -0.10, 95% confidence interval -0.17 to -0.04), after adjusting for age, sex, race-ethnicity, education, insurance, depressed mood, stroke severity, bladder continence, and stroke laterality. This decline remained when BI >/=95 was added to the model as a time-dependent covariate, and functional status also predicted QLI. Changes in QLI over time differed by insurance status (p for interaction = 0.0017), with a decline for those with Medicaid/no insurance (p < 0.0001) but not Medicare/private insurance (p = 0.98). CONCLUSIONS: In this population-based study, QOL declined annually up to 5 years after stroke among survivors free of recurrence or MI and independently of other risk factors. QLI declined more among Medicaid patients and was associated with age, mood, stroke severity, urinary incontinence, functional status, cognition, and stroke laterality. PMID- 20574035 TI - One gene, one or many diseases? Simplifying dysferlinopathy. PMID- 20574036 TI - Surrogate endpoints for EDSS worsening in multiple sclerosis. A meta-analytic approach. AB - OBJECTIVE: To evaluate whether the effects on potential surrogate endpoints, such as MRI markers and relapses, observed in trials of experimental treatments are able to predict the effects of these treatments on disability progression as defined in relapsing-remitting multiple sclerosis (RRMS) trials. METHODS: We used a pooled analysis of all the published randomized controlled clinical trials in RRMS reporting data on Expanded Disability Status Scale (EDSS) worsening and relapses or MRI lesions or both. We extracted data on relapses, MRI lesions, and the proportion of progressing patients. A regression analysis weighted on trial size and duration was performed to study the relationship between the treatment effect observed in each trial on relapses and MRI lesions and the observed treatment effect on EDSS worsening. RESULTS: A set of 19 randomized double-blind controlled trials in RRMS were identified, for a total of 44 arms, 25 contrasts, and 10,009 patients. A significant correlation was found between the effect of treatments on relapses and the effect of treatments on EDSS worsening: the adjusted R(2) value of the weighted regression was 0.71. The correlation between the treatment effect on MRI lesions and EDSS worsening was slightly weaker (R(2) = 0.57) but significant. CONCLUSIONS: These findings support the use of commonly used surrogate markers of EDSS worsening as endpoints in multiple sclerosis clinical trials. Further research is warranted to validate surrogate endpoints at the individual level rather than at the trial level, to draw important conclusions in the management of the individual patient. PMID- 20574037 TI - Redefining dysferlinopathy phenotypes based on clinical findings and muscle imaging studies. AB - BACKGROUND: The most frequent phenotypes of dysferlin myopathy are limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy (MM). Our objective was to find clinical or MRI markers to differentiate phenotypes of dysferlin myopathy regardless of initial symptoms. METHODS: This retrospective study included 29 patients with confirmed mutations in the DYSF gene (14 MM, 12 LGMD2B, 1 asymptomatic hyperCKemia, and 2 symptomatic carriers). All underwent an annual clinical examination (Medical Research Council scale), functional status assessment, and creatine kinase, pulmonary, and cardiac testing. For research purposes, we performed lower limb MRI studies in all 29 patients to identify the pattern of muscle impairment and to quantify involvement. Statistical correlations between MRI findings and phenotype, disease duration, and functional status were determined. RESULTS: The mean clinical follow-up was 6.4 +/- 5.7 years. No significant differences were found in the rate of progression, functional prognosis, or mutations between patients with MM and patients with LGMD2B. The MRI pattern of muscle involvement was the same for patients with MM and patients with LGMD2B. The adductor magnus and gastrocnemius medialis were the first to be impaired in both phenotypes. The progression of muscle involvement correlated with clinical status. CONCLUSIONS: Splitting dysferlin myopathy into separate phenotypes does not reveal significant differences in terms of rate of progression, prognosis, genotype, or MRI pattern. The finding that proximal and distal muscles are already impaired in the MRI at onset in both MM and LGMD2B favors grouping all phenotypes under the term dysferlin myopathy. PMID- 20574038 TI - Predicting falls in Parkinson disease: a step in the right direction. PMID- 20574039 TI - Predictors of future falls in Parkinson disease. AB - BACKGROUND: Falls are a major health and injury problem for people with Parkinson disease (PD). Despite the severe consequences of falls, a major unresolved issue is the identification of factors that predict the risk of falls in individual patients with PD. The primary aim of this study was to prospectively determine an optimal combination of functional and disease-specific tests to predict falls in individuals with PD. METHODS: A total of 101 people with early-stage PD undertook a battery of neurologic and functional tests in their optimally medicated state. The tests included Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk; the latter assessment includes physiologic tests of visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway. Falls were recorded prospectively over 6 months. RESULTS: Forty-eight percent of participants reported a fall and 24% more than 1 fall. In the multivariate model, a combination of the Unified Parkinson's Disease Rating Scale (UPDRS) total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction produced the best sensitivity (78%) and specificity (84%) for predicting falls. From the UPDRS items, only the rapid alternating task category was an independent predictor of falls. Reduced peripheral sensation and knee extension strength in fallers contributed to increased postural instability. CONCLUSIONS: Falls are a significant problem in optimally medicated early-stage PD. A combination of both disease-specific and balance- and mobility-related measures can accurately predict falls in individuals with PD. PMID- 20574040 TI - Race and ethnicity and breast cancer outcomes in an underinsured population. AB - BACKGROUND: The disparity in breast cancer mortality between African American women and non-Hispanic white women has been the subject of increased scrutiny. Few studies have addressed these differences in the setting of equal access to health care. We compared the breast cancer outcomes of underinsured African American and non-Hispanic white patients who were treated at a single institution. METHODS: We conducted a retrospective review of medical records for breast cancer patients who were treated at Wishard Memorial Hospital from January 1, 1997, to February 28, 2006. A total of 574 patients (259 non-Hispanic whites and 315 African Americans) were evaluated. A Cox proportional hazards regression analysis for competing risks was performed. All statistical tests were two-sided. RESULTS: Sociodemographic characteristics were similar in the two groups, and both racial groups were equally unlikely to have undergone screening mammography during the 2 years before diagnosis. Most (84%) of the patients were underinsured. The median time from diagnosis to operation, receipt of adequate surgery, and use of all types of adjuvant therapy were similar in the two groups. Median follow-up was 80.3 months for non-Hispanic whites and 77.9 months for African Americans. After accounting for the effect of comorbidities, African American race was statistically significantly associated with breast cancer specific mortality (African Americans vs non-Hispanic whites: 26.0% vs 17.5%, P = .028; hazard ratio [HR] of death = 1.64, 95% confidence interval [CI] = 1.06 to 2.55). Adjustment for age at diagnosis, clinical stage, and hormone receptor status attenuated the effect, and the effect of race on breast cancer-specific survival was no longer statistically significant (HR of death from breast cancer = 1.43, 95% CI = 0.89 to 2.30). After adjustment for sociodemographic factors, the hazard ratio for race was further attenuated (HR = 1.26; 95% CI = 0.79 to 2.00). CONCLUSIONS: In this underinsured population, African American patients had poorer breast cancer-specific survival than non-Hispanic white patients. After adjustment for clinical and sociodemographic factors, the effect of race on survival was no longer statistically significant. PMID- 20574041 TI - Re-visiting the endogenous capacity for recombinant glycoprotein sialylation by baculovirus-infected Tn-4h and DpN1 cells. AB - It was previously reported that Tn-4h and DpN1 cells have the endogenous capacity to efficiently sialylate secreted alkaline phosphatase (SEAP) when infected with a baculovirus expression vector. In contrast, it has been found that lepidopteran insect cell lines that are more widely used as hosts for baculovirus vectors typically fail to sialylate SEAP and other recombinant glycoproteins. Thus, the N glycan processing capabilities of Tn-4h and DpN1 cells are of potential interest to investigators using the baculovirus expression system for recombinant glycoprotein production. In this study, we experimentally re-assessed the ability of Tn-4h and DpN1 cells to sialylate SEAP with Sf9 and glyco-engineered Sf9 cells (SfSWT-1) as negative and positive controls, respectively. Our results showed that the SEAP purified from SfSWT-1 cells was strongly sialylated and initially indicated that the SEAP purified from Tn-4h cells was weakly sialylated. However, further analyses suggested that the SEAP produced by Tn-4h cells only appeared to be sialylated because it was contaminated with an electrophoretically indistinguishable sialoglycoprotein derived from fetal bovine serum. We subsequently expressed, purified, and analyzed a second recombinant glycoprotein (GST-SfManI) from all four cell lines and found that only the SfSWT-1 cells were able to detectably sialylate this product. Together, these results showed that neither Tn-4h nor DpN1 cells efficiently sialylated SEAP or GST-SfManI when infected by baculovirus expression vectors. Furthermore, they suggested that previous reports of efficient SEAP sialylation by Tn-4h and DpN1 cells probably reflect contamination with a sialylated, co-migrating glycoprotein, perhaps bovine fetuin, derived from the serum used in the insect cell growth medium. PMID- 20574042 TI - Beta4-galactosyltransferase-5 is a lactosylceramide synthase essential for mouse extra-embryonic development. AB - Glycosphingolipids (GSLs) are important for various biological functions in the nervous system, the immune system, embryogenesis and in other tissues and processes. Lactosylceramide (LacCer), which is synthesized from glucosylceramide (GlcCer) by LacCer synthase, is a core structure of GSLs, including gangliosides. LacCer synthase was reported to be synthesized by the beta4-galactosyltransferase 6 (beta4GalT-6) gene in the rat brain. However, the existence of another LacCer synthase gene was shown in cultured cells lacking beta4GalT-6. Here, we report that LacCer synthase is mainly synthesized by the beta4GalT-5 gene during early mouse embryogenesis, and its disruption is embryonic lethal. beta4GalT-5 deficient embryos showed developmental retardation from E7.5 and died by E10.5 as reported previously. LacCer synthase activity was significantly reduced in beta4GalT-5-deficient embryos and extra-embryonic endoderm (XEN) cells derived from blastocysts, and it was recovered when beta4GalT-5 cDNA was introduced into beta4GalT-5-deficient XEN cells. The amounts of LacCer and GM3 ganglioside were drastically reduced, while GlcCer accumulated in the beta4GalT-5-deficient XEN cells. Hematoma and ectopically accumulated trophoblast giant cells were observed in the anti-mesometrial pole of the extra-embryonic tissues, although all three embryonic layers formed. beta4GalT-5-deficient embryos developed until E12.5 as chimeras with wild-type tetraploid cells, which formed the extra-embryonic membranes, indicating that extra-embryonic defects caused the early embryonic lethality. Our results suggest that beta4GalT-5 is essential for extra-embryonic development during early mouse embryogenesis. PMID- 20574043 TI - Glycomimicry: display of the GM3 sugar epitope on Escherichia coli and Salmonella enterica sv Typhimurium. AB - Oligosaccharides present on the surface of pathogenic bacteria play an important role in their interaction with their host. Bacteria with altered cell surface structures can be used to study these interactions, and glycoengineering represents a tool to display a glycoepitope on a different bacterium. Here, we present non-pathogenic Escherichia coli and Salmonella enterica serovar Typhimurium expressing the sialyllactose oligosaccharide epitope of the ganglioside GM3. By expression of the galactosyltransferase LgtE and the sialic acid transferase Lst as well as the CMP-sialic acid synthetase SiaB from Neisseria gonorrhoeae and Neisseria meningitidis in engineered strains devoid of the sialic acid catabolism, the GM3 sugar epitope was displayed on these bacteria as demonstrated by live cell immunostaining and a detailed analysis of their lipooligosaccharides. These strains offer the possibility to investigate the role of sialic acid in the recognition of bacteria by the immune system in a non pathogenic background. PMID- 20574044 TI - Retraction. Sawada S, Ishikawa C, Tanji H, Nakachi S, Senba M, Okudaira T, Uchihara J-N, Taira N, Ohshiro K, Yamada Y, Tanaka Y, Uezato H, Ohshima K, Sasai K, Burgering BMT, Duc Dodon M, Fujii M, Sunakawa H, Mori N. Overexpression of caveolin-1 in adult T-cell leukemia. Blood. 2010; 115(11):2220-2230. PMID- 20574045 TI - Retraction. Tanji H, Ishikawa C, Sawada S, Nakachi S, Takamatsu R, Matsuda T, Okudaira T, Uchihara J-N, Ohshiro K, Tanaka Y, Senba M, Uezato H, Ohshima K, Duc Dodon M, Wu K-J, Mori N. Aberrant expression of the transcription factor Twist in adult T-cell leukemia [published online ahead of print January 13, 2010]. Blood. doi:10.1182/blood-2009-07-232231. PMID- 20574046 TI - Properties of CD34+ CML stem/progenitor cells that correlate with different clinical responses to imatinib mesylate. AB - Imatinib mesylate (IM) induces clinical remissions in chronic-phase chronic myeloid leukemia (CML) patients but IM resistance remains a problem. We recently identified several features of CML CD34(+) stem/progenitor cells expected to confer resistance to BCR-ABL-targeted therapeutics. From a study of 25 initially chronic-phase patients, we now demonstrate that some, but not all, of these parameters correlate with subsequent clinical response to IM therapy. CD34(+) cells from the 14 IM nonresponders demonstrated greater resistance to IM than the 11 IM responders in colony-forming cell assays in vitro (P < .001) and direct sequencing of cloned transcripts from CD34(+) cells further revealed a higher incidence of BCR-ABL kinase domain mutations in the IM nonresponders (10%-40% vs 0%-20% in IM responders, P < .003). In contrast, CD34(+) cells from IM nonresponders and IM responders were not distinguished by differences in BCR-ABL or transporter gene expression. Interestingly, one BCR-ABL mutation (V304D), predicted to destabilize the interaction between p210(BCR-ABL) and IM, was detectable in 14 of 20 patients. T315I mutant CD34(+) cells found before IM treatment in 2 of 20 patients examined were preferentially amplified after IM treatment. Thus, 2 properties of pretreatment CML stem/progenitor cells correlate with subsequent response to IM therapy. Prospective assessment of these properties may allow improved patient management. PMID- 20574047 TI - Crucial roles of B7-H1 and B7-DC expressed on mesenteric lymph node dendritic cells in the generation of antigen-specific CD4+Foxp3+ regulatory T cells in the establishment of oral tolerance. AB - Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to fed antigens. However, the molecular mechanism mediating oral tolerance remains unclear. In this study, we examined the role of the B7 family members of costimulatory molecules in the establishment of oral tolerance. Deficiencies of B7-H1 and B7-DC abrogated the oral tolerance, accompanied by enhanced antigen-specific CD4(+) T-cell response and IgG(1) production. Mesenteric lymph node (MLN) dendritic cells (DCs) displayed higher levels of B7 H1 and B7-DC than systemic DCs, whereas they showed similar levels of CD80, CD86, and B7-H2. MLN DCs enhanced the antigen-specific generation of CD4(+)Foxp3(+) inducible regulatory T cells (iT(regs)) from CD4(+)Foxp3(-) T cells rather than CD4(+) effector T cells (T(eff)) relative to systemic DCs, owing to the dominant expression of B7-H1 and B7-DC. Furthermore, the antigen-specific conversion of CD4(+)Foxp3(-) T cells into CD4(+)Foxp3(+) iT(regs) occurred in MLNs greater than in peripheral organs during oral tolerance under steady-state conditions, and such conversion required B7-H1 and B7-DC more than other B7 family members, whereas it was severely impaired under inflammatory conditions. In conclusion, our findings suggest that B7-H1 and B7-DC expressed on MLN DCs are essential for establishing oral tolerance through the de novo generation of antigen-specific CD4(+)Foxp3(+) iT(regs). PMID- 20574048 TI - Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. AB - Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). The authors of previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy-induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both all trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease. PMID- 20574049 TI - Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells. AB - Chronic lymphocytic leukemia (CLL) is an incurable progressive disease for which new therapies are required. Therapy with monoclonal antibodies (mAbs) has improved the outcome of patients with CLL, making further investigation of novel antibodies directed against alternative and specific targets on B cells an important area of translational research. We now describe functional properties of an antagonistic humanized mAb to CD74, milatuzumab, showing that milatuzumab combined with a crosslinking antibody induces cytotoxicity in vitro in CLL cells in a caspase- and stromal-independent manner associated with aggregation of CD74 on the cell surface. Furthermore, incorporation of milatuzumab into an immunoliposome induces even more of a cytotoxic response than in vitro crosslinking, representing a novel therapeutic formulation for this mAb. Based on these data, future development of the milatuzumab-immunoliposome formulation as a therapeutic agent for CLL is warranted. PMID- 20574050 TI - Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. AB - To identify molecularly defined subgroups in multiple myeloma, gene expression profiling was performed on purified CD138(+) plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/GMMG-HD4 trial. Hierarchical clustering identified 10 subgroups; 6 corresponded to clusters described in the University of Arkansas for Medical Science (UAMS) classification, CD-1 (n = 13, 4.1%), CD-2 (n = 34, 1.6%), MF (n = 32, 1.0%), MS (n = 33, 1.3%), proliferation-associated genes (n = 15, 4.7%), and hyperdiploid (n = 77, 24.1%). Moreover, the UAMS low percentage of bone disease cluster was identified as a subcluster of the MF cluster (n = 15, 4.7%). One subgroup (n = 39, 12.2%) showed a myeloid signature. Three novel subgroups were defined, including a subgroup of 37 patients (11.6%) characterized by high expression of genes involved in the nuclear factor kappa light-chain-enhancer of activated B cells pathway, which include TNFAIP3 and CD40. Another subgroup of 22 patients (6.9%) was characterized by distinct overexpression of cancer testis antigens without overexpression of proliferation genes. The third novel cluster of 9 patients (2.8%) showed up-regulation of protein tyrosine phosphatases PRL-3 and PTPRZ1 as well as SOCS3. To conclude, in addition to 7 clusters described in the UAMS classification, we identified 3 novel subsets of multiple myeloma that may represent unique diagnostic entities. PMID- 20574051 TI - Uterine adenogenesis and pregnancy: multiple roles for Foxa2 in mice. PMID- 20574052 TI - Ovine surgical model of uterine space restriction: interactive effects of uterine anomalies and multifetal gestations on fetal and placental growth. AB - Intrauterine growth restriction (IUGR) is observed in conditions with limitations in uterine space (e.g., uterine anomalies and multifetal gestations). IUGR is associated with reduced fetal weight, organ growth, and a spectrum of adult-onset diseases. To examine the interaction of uterine anomalies and multifetal gestations, we developed a surgical uterine space restriction model with a unilateral uterine horn ligation before breeding (unilateral surgery). Placentas and fetuses were studied on Gestational Day (GD) 120 and GD 130 (term = 147 days). Unilateral surgery decreased placentome numbers in singleton and twin pregnancies (25% and 50%, respectively) but not unilateral triplets. Unilateral surgery decreased total placentome weight in twin pregnancies (decreased 24%). Fetuses categorized as uterine space restricted (unilateral twin and both groups of triplets) had 51% fewer placentomes per fetus and a 31% reduction in placentomal weight per fetus compared to the nonrestricted group (control singleton, unilateral singleton, and control twin). By GD 130, uterine space restricted fetuses exhibited decreased weight, smaller crown-rump, abdominal girth, and thoracic girth as well as decreased fetal heart, kidney, liver, spleen, and thymus weights. Lung and brain weights were unaffected, demonstrating asymmetric IUGR. At GD 130, placental efficiency (fetal weight per total placentomal weight) was elevated in uterine space-restricted fetuses. However, fetal arterial creatinine, blood urea nitrogen, and cholesterol were elevated, suggesting insufficient placental clearance. Maternal-to-fetal glucose and triglycerides ratios were elevated in the uterine space-restricted pregnancies, suggesting placental nutrient transport insufficiency. This model allows for examination of interactive effects of uterine space restriction-induced IUGR on placental adaptation and fetal organ growth. PMID- 20574053 TI - Identification and quantification of dopamine receptor 2 in human eutopic and ectopic endometrium: a novel molecular target for endometriosis therapy. AB - Previous studies in an experimental mouse model of endometriosis have shown that the dopamine agonist (DA) cabergoline (Cb2) reduces angiogenesis and endometriotic lesions, hypothetically binding to the dopamine receptor type-2 (DRD2). To date, this has not been described in human endometrium and/or endometriotic lesions. Thus, we aimed to investigate the presence of DRD2 in said tissues. Endometrium fragments were implanted in nude mice treated with different doses of Cb2. Polymerase chain reaction assays and immunohistochemistry were performed to analyze the gene and protein expressions (respectively) of DRD2, VEGF, and VEGF receptor-2 (KDR). In addition, lesions and endometrium from women with mild and severe endometriosis and endometrium from healthy women were collected to analyze their gene expression profile. In experimental endometriosis, DRD2 was expressed at gene and protein levels in all three groups. VEGF gene and protein expressions were significantly lower in lesions treated with Cb2 than in controls. KDR protein expression was significantly lower in experimental lesions treated with Cb2 than in controls. In eutopic endometria, there was a significant decrease in DRD2 expression and an increase in VEGF in women with mild and severe endometriosis with respect to healthy patients. In endometriosis, KDR expression was significantly higher in red than in white and black lesions. VEGF expression was significantly lower in black than in red lesions. DRD2 is present in the human eutopic and ectopic endometrium and is regulated by DA, which provides the rationale for pilot studies to explore its use in the treatment of endometriosis. PMID- 20574055 TI - Differential contribution of the MTOR and MNK pathways to the regulation of mRNA translation in meiotic and postmeiotic mouse male germ cells. AB - Translation of stored mRNAs accounts for protein synthesis during the transcriptionally inactive stages of spermatogenesis. A key step in mRNA translation is the assembly of the initiation complex EIF4F, which is regulated by the MTOR (mammalian target of rapamycin) and MNK1/2 (MAP kinase-interacting kinase 1 and 2) pathways. We investigated the expression and activity of regulatory proteins of these pathways in male germ cells at different stages of differentiation. All translation factors analyzed were expressed in germ cells throughout spermatogenesis. However, while EIF4G and PABP1 (poly[A]-binding protein 1) were more abundant in postmeiotic cells, MTOR and its target EIF4EBP1 (4E-BP1) decreased steadily during spermatogenesis. In vivo labeling showed that pachytene spermatocytes display higher rates of protein synthesis, which are partially dependent on MTOR and MNK activity. By contrast, haploid spermatids are characterized by lower levels of protein synthesis, which are independent of the activity of these pathways. Accordingly, MTOR and MNK activity enhanced formation of the EIF4F complex in pachytene spermatocytes but not in round spermatids. Moreover, external cues differentially modulated the activity of these pathways in meiotic and haploid cells. Heat shock decreased MTOR and MNK activity in pachytene spermatocytes, whereas round spermatids were much less sensitive. On the other hand, treatment with the phosphatase inhibitor okadaic acid activated MTOR and MNK in both cell types. These results indicate that translational regulation is differentially dependent on the MTOR and MNK pathways in mouse spermatocytes and spermatids and suggest that the late stages of germ cell differentiation display constitutive assembly of the translation initiation complex. PMID- 20574054 TI - Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human primate. AB - Kisspeptin, the product of the KISS1 gene, stimulates gonadotropin-releasing hormone (GnRH) secretion; gonadotropin inhibitory hormone (GnIH), encoded by the RF-amide-related peptide (RFRP) or NPVF gene, inhibits the reproductive axis. In sheep, kisspeptin neurons are found in the lateral preoptic area (POA) and the arcuate nucleus (ARC) and may be important for initiating the preovulatory GnRH/luteinizing hormone (LH) surge. GnIH cells are located in the ovine dorsomedial hypothalamic nucleus (DMN) and paraventricular nucleus (PVN), with similar distribution in the primate. KISS1 cells are found in the primate POA and ARC, but the function that kisspeptin and GnIH play in primates has not been elucidated. We examined KISS1 and NPVF mRNA throughout the menstrual cycle of a female primate, rhesus macaque (Macaca mulatta), using in situ hybridization. KISS1-expressing cells were found in the POA and ARC, and NPVF-expressing cells were located in the PVN/DMN. KISS1 expression in the caudal ARC and POA was higher in the late follicular phase of the cycle (just before the GnRH/LH surge) than in the luteal phase. NPVF expression was also higher in the late follicular phase. We ascertained whether kisspeptin and/or GnIH cells project to GnRH neurons in the primate. Close appositions of kisspeptin and GnIH fibers were found on GnRH neurons, with no change across the menstrual cycle. These data suggest a role for kisspeptin in the stimulation of GnRH cells before the preovulatory GnRH/LH surge in non-human primates. The role of GnIH is less clear, with paradoxical up-regulation of gene expression in the late follicular phase of the menstrual cycle. PMID- 20574056 TI - Effect of lisdexamfetamine dimesylate on sleep in children with ADHD. AB - OBJECTIVE: This study evaluated the potential effects of short-term treatment with lisdexamfetamine dimesylate (LDX) on both subjective and objective sleep characteristics in children aged 6 to 12 years (n = 24) with ADHD. METHOD: Polysomnography (PSG) and actigraph measures as well as assessments of subjective sleep parameters were examined in children before and after treatment with either LDX or placebo in a randomized, double-blind, single-center, parallel-group study. RESULTS: There was no statistically significant increase in the primary endpoint of latency to persistent sleep (LPS) for the LDX-treated group compared to the placebo group. Secondary PSG or actigraph results generally supported primary endpoint results. Subjective sleep measure results indicated the possibility that responses are influenced by sleep hygiene counseling before and throughout the study. CONCLUSIONS: In this pilot sleep study in children with ADHD, LDX did not appear to contribute to any sleep disturbances as measured by both objective and subjective sleep parameters. The sample used in this study was small, and the multifarious nature of findings in this study warranted that the study conclusions be interpreted cautiously and that further study is required focusing on the influence of LDX on sleep in larger samples of ADHD children. PMID- 20574057 TI - Working memory deficits in ADHD: the contribution of age, learning/language difficulties, and task parameters. AB - OBJECTIVE: To further define the nature of working memory (WM) impairments in children with combined-type ADHD. METHOD: A total of 40 Children with ADHD and an age and gender-matched control group (n = 40) completed two measures of visuo spatial WM and two measures of verbal WM. The effects of age and learning/language difficulties on performance were evaluated. RESULTS: Children with ADHD obtained significantly lower scores than controls on measures of both visuo-spatial and verbal WM. The impairments in verbal WM were age related. CONCLUSION: Children with ADHD exhibit impaired visuo-spatial WM performance. Younger (less than 8 years), but not older, children with ADHD demonstrate impairments in verbal WM. This latter result may explain the previously reported inconsistent performance of children with ADHD on verbal WM tasks. The importance of taking a developmental perspective in WM research is stressed. PMID- 20574058 TI - Influence of anxiety on the social functioning of children with and without ADHD. AB - OBJECTIVE: This investigation examined the contribution of anxiety to the social functioning of children with and without ADHD. METHOD: Participants were 62 children with ADHD (ages 6-10 years and 68% boys) and 62 age- and sex-matched comparison children. Children's social functioning was measured through parent and teacher reports, observations of social behaviors during a lab-based playgroup with previously unacquainted peers, and peer nominations during that lab-based playgroup. RESULTS: Anxiety symptoms incrementally predicted adult informant reports of poorer social functioning after controlling for demographic covariates, ADHD status, and oppositional-defiant disorder (ODD) status. However, anxiety was not associated with peer nominations received at the playgroup. There were some indications that anxiety may have greater influence on the functioning of comparison children relative to children with ADHD or ODD. CONCLUSION: Anxiety may contribute to the peer problems of children both with and without ADHD. PMID- 20574059 TI - Comorbidity of asthma with ADHD. AB - OBJECTIVE: To assess how frequently drugs used to treat asthma and ADHD are prescribed to the same patients. METHOD: The authors used data from the Norwegian Prescription Database for 2006, including the total Norwegian population (n = 4,640,219). RESULTS: Anti-asthma drugs were prescribed to 350,894 persons (7.56 % of the population), anti-ADHD drugs to 18,481 persons (0.40 %), and both to 1,730 persons. There was a 65% increased overall risk (OR = 1.65) of being prescribed one of the drugs given a prescription of the other. Women had a markedly higher risk than men. When data for each age group (10 years interval) and each gender were analyzed separately, the strongest associations were found for women between 20 and 49 years of age and men between 30 and 49 years of age. CONCLUSION: These prescription patterns suggested a marked comorbidity between asthma and ADHD. PMID- 20574060 TI - Psychosocial experiences associated with confirmed and self-identified dyslexia: a participant-driven concept map of adult perspectives. AB - Concept mapping (a mixed qualitative-quantitative methodology) was used to describe and understand the psychosocial experiences of adults with confirmed and self-identified dyslexia. Using innovative processes of art and photography, Phase 1 of the study included 15 adults who participated in focus groups and in depth interviews and were asked to elucidate their experiences with dyslexia. On index cards, 75 statements and experiences with dyslexia were recorded. The second phase of the study included 39 participants who sorted these statements into self-defined categories and rated each statement to reflect their personal experiences to produce a visual representation, or concept map, of their experience. The final concept map generated nine distinct cluster themes: Organization Skills for Success; Finding Success; A Good Support System Makes the Difference; On Being Overwhelmed; Emotional Downside; Why Can't They See It?; Pain, Hurt, and Embarrassment From Past to Present; Fear of Disclosure; and Moving Forward. Implications of these findings are discussed. PMID- 20574061 TI - An examination of multiple predictors of orthographic functioning. AB - The purpose of this study was to compare three variables in terms of how well they predict orthographic functioning. To this end, the authors examined the relative contributions of rapid automatic naming, exposure to print, and visual processing to a composite measure of orthographic functioning in a heterogeneous group of 8- to 12-year-old children. Hierarchical regression analyses revealed that rapid naming, exposure to print, and visual processing were each predictive of orthographic functioning when controlling for the other variables as well as vocabulary knowledge and phonological awareness. Thus, it appears that both linguistic and visual abilities are related to orthographic functioning. PMID- 20574062 TI - Social cognition and its relation to psychosocial adjustment in children with nonverbal learning disabilities. AB - The current study examined social cognitive skills in children with nonverbal learning disabilities (NLD) compared to normally achieving (NA) children. The relation between social cognitive skills and psychosocial adjustment was also investigated. There were no group differences on children's ability to represent orally presented social vignettes. Children with NLD were less able to recognize self-generated competent/assertive responses as the best solutions to a problem, expected fewer positive and more negative outcomes for examiner-provided competent responses, and showed a trend toward more frequently judging a story character as being mean. A social problem solving factor predicted unique variance in psychosocial adjustment beyond variance accounted for by nonverbal intelligence and nonverbal social cue interpretation. Results are discussed within a framework for which social cognitive deficits more broadly defined than encoding and interpreting nonverbal social cues contribute to the psychosocial adjustment problems of children with NLD. PMID- 20574063 TI - Patterns of cognitive impairments among heroin and cocaine users: the association with self-reported learning disabilities and infectious disease. AB - This study used data from six neuropsychological measures of executive function (EF) and general intellectual functioning (GIF) administered to 303 regular users of heroin and/or cocaine as indicators in a latent profile analysis (LPA). Results indicated the presence of three profiles: impaired GIF and EF profile (30.8%), intact GIF and EF profile (58.8%), and high GIF/intact EF profile (10.4%). Using a multinomial logistic regression, it was determined that individuals who reported being diagnosed with either a learning disability (LD) and/or attention-deficit/hyperactivity disorder (ADHD) were more likely to be in the impaired GIF and EF profile than other profiles. Results from a logistic regression indicated that the impaired GIF and EF profile was associated with a greater prevalence of past hepatitis B and/or C infection. Implication for harm reduction and treatment programs and the need to take into account individuals with LD and ADHD are discussed. PMID- 20574064 TI - A short report: Word-level phonological and lexical characteristics interact to influence phoneme awareness. AB - In this study, we examined the influence of word-level phonological and lexical characteristics on early phoneme awareness. Typically developing children, ages 61 to 78 months, completed a phoneme-based, odd-one-out task that included consonant-vowel-consonant word sets (e.g., "chair-chain-ship") that varied orthogonally by a phonological characteristic, sound contrast similarity (similar vs. dissimilar), and a lexical characteristic, neighborhood density (dense vs. sparse). In a subsample of the participants-those with the highest vocabularies results were in line with a predicted interactive effect of phonological and lexical characteristics on phoneme awareness performance: word sets contrasting similar sounds were less likely to yield correct responses in words from sparse neighborhoods than words from dense neighborhoods. Word sets contrasting dissimilar sounds were most likely to yield correct responses regardless of the words' neighborhood density. Based on these findings, theories of early phoneme awareness should consider both word-level and child-level influences on performance. Attention to these influences is predicted to result in more sensitive and specific measures of reading risk. PMID- 20574065 TI - Patient-Centered Outcomes Research Institute: the intersection of science and health care. AB - The Patient Protection and Affordable Care Act created the Patient-Centered Outcomes Research Institute (PCORI), a nonprofit corporation that is neither an agency nor an establishment of the U.S. government. PCORI's mission is to support the production of well-validated scientific evidence to assist the nation in making informed decisions about a broad range of health care-related issues. In this Commentary, the directors of the Agency for Healthcare Research and Quality and the National Institutes of Health discuss PCORI's opportunities to contribute to a robust portfolio of scientific inquiry that builds on their agencies' investment in comparative effectiveness research. PMID- 20574066 TI - Multidimensional results reporting to participants in genomic studies: getting it right. AB - Recent surveys about participation in cohort studies reconfirm that participants value and desire the return of research results to a degree that is out of step with the restrictive recommendations of various ethics advisory groups, which have historically limited disclosure based on clinician value judgments and the severity and treatability of the disease in question, among other factors. Rather than framing the current inconclusive ethics discussion as a standstill among competing ethical principles and their potential applicability, we introduce a new element, communicability (that is, those properties of a message that will determine how likely it is that its informational intent will be grasped by the study participant), as the subject of empirical research to align participants' goals with beneficent and responsible results reporting. Structural changes in research design, combined with governance changes in assessing impact, allow us to move beyond a binary construction of report/do not report and to create a structure in which the communicability of the message and the participants' preferences are variables in a function that affects results reporting. Here we illustrate this structure and its principles. PMID- 20574067 TI - Alternative control: what's WASp doing in the nucleus? AB - Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive immunodeficiency disorder of childhood that is caused by mutations in the WAS gene. WAS encodes WASp, a protein that is known to function in the cytoplasm of hematopoietic cells and is required for the induced differentiation of CD4+ T helper type 1 (TH1) lymphocytes. Now, a paper in Science Translational Medicine describes another mechanism for impaired immunity in WAS by showing that WASp localizes in the nucleus and regulates histone modifications and chromatin structure, thereby modulating expression of the TH1 master gene TBX21 (TBET). PMID- 20574070 TI - Cerebral and renal phaeohyphomycosis in a dog infected with Bipolaris species. AB - Mycotic meningoencephalitis in dogs may manifest as a primary disease of the central nervous system or as a part of disseminated infection. Fungi belonging to the genus Bipolaris are saprophytic plant pathogens and can cause disease in humans. The authors report a case of Bipolaris infection in a dog with granulomatous meningoencephalitis, nephritis, and vasculitis. The clinical and histological features resembled those of the more common aspergillosis, thus warranting confirmation by molecular methods. Polymerase chain reaction and sequence analysis identified Bipolaris from the brain lesion, indicating its involvement in the disease. To the authors' knowledge, this is the first reported case of meningoencephalitis caused by this fungus in a domestic animal. PMID- 20574068 TI - Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. AB - The clinical symptomatology in the X-linked Wiskott-Aldrich syndrome (WAS), a combined immunodeficiency and autoimmune disease resulting from WAS protein (WASp) deficiency, reflects the underlying coexistence of an impaired T helper 1 (TH1) immunity alongside intact TH2 immunity. This suggests a role for WASp in patterning T(H) subtype immunity, yet the molecular basis for the TH1-TH2 imbalance in human WAS is unknown. We have discovered a nuclear role for WASp in the transcriptional regulation of the TH1 regulator gene TBX21 at the chromatin level. In primary TH1-differentiating cells, a fraction of WASp is found in the nucleus, where it is recruited to the proximal promoter locus of the TBX21 gene, but not to the core promoter of GATA3 (a TH2 regulator gene) or RORc (a TH17 regulator gene). Genome-wide mapping demonstrates association of WASp in vivo with the gene-regulatory network that orchestrates TH1 cell fate choice in the human TH cell genome. Functionally, nuclear WASp associates with H3K4 trimethyltransferase [RBBP5 (retinoblastoma-binding protein 5)] and H3K9/H3K36 tridemethylase [JMJD2A (Jumonji domain-containing protein 2A)] proteins, and their enzymatic activity in vitro and in vivo is required for achieving transcription-permissive chromatin dynamics at the TBX21 proximal promoter in primary differentiating TH1 cells. During TH1 differentiation, the loss of WASp accompanies decreased enrichment of RBBP5 and, in a subset of WAS patients, also of filamentous actin at the TBX21 proximal promoter locus. Accordingly, human WASp-deficient TH cells, from natural mutation or RNA interference-mediated depletion, demonstrate repressed TBX21 promoter dynamics when driven under TH1 differentiating conditions. These chromatin derangements accompany deficient T BET messenger RNA and protein expression and impaired TH1 function, defects that are ameliorated by reintroducing WASp. Our findings reveal a previously unappreciated role of WASp in the epigenetic control of T-BET transcription and provide a new mechanism for the pathogenesis of WAS by linking aberrant histone methylation at the TBX21 promoter to dysregulated adaptive immunity. PMID- 20574071 TI - Diagnostic exercise: chronic vomiting in a dog. AB - An approximately one-and-a-half-year-old, neutered male, mixed-breed dog was presented for a chronic history of vomiting. Profuse diarrhea was also noted during examination. An exploratory laparotomy was performed, bone chips were removed from the stomach, and a raised, circular area of gastric mucosa was biopsied. Histologically, there was severe gastric cryptosporidiosis as well as numerous spiral bacteria, consistent with Helicobacter spp. Polymerase chain reaction revealed visible bands for the 18S ribosomal RNA gene for Cryptosporidium spp. The polymerase chain reaction product was sequenced and was found to be most similar to Cryptosporidium muris. Both the gastric location and the species of Cryptosporidium are unusual in a dog. PMID- 20574069 TI - Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates. AB - Most heart attacks and strokes are caused by blood clots (thrombi) that block the vasculature. Because disease-causing arterial thrombosis depends on blood platelets, platelet inhibitors such as aspirin and clopidogrel effectively decrease the risk of thrombosis; however, they also impair platelet-dependent hemostasis that staunches bleeding from wounds and can therefore produce excessive bleeding. Experimental studies show that a reduction in the number of platelets also inhibits thrombosis, but these treatments also interfere with platelet function. Because normal hemostasis requires that the platelet concentration remain within a physiological range in the circulation, we evaluated whether lowering the number of circulating platelets--but only to a value still within the normal range--by inhibiting platelet formation in the bone marrow inhibits acute thrombogenesis in baboons. We reduced the platelet count with an inhibitor against the megakaryocyte-promoting hormone thrombopoietin and then showed that experimental occlusive thrombogenesis on collagen-coated vascular grafts was reduced, without impairment of primary hemostasis. These results suggest that suppressing platelet production without interfering with the hemostatic function of platelets may offer a safe alternative to current therapies for prevention of stroke and heart attack triggered by blood clotting. PMID- 20574072 TI - Cardiac angioleiomyoma in 44 cattle in Japan (1982-2009). AB - A retrospective study was performed on primary cardiac tumors found in 44 cattle during meat inspection in Japan, using histology, immunohistochemistry, and electron microscopy. The age of affected cattle ranged from 10 to 129 months; 82% were less than 3 years old. In 38 hearts, the tumor was solitary; the remaining 6 hearts had multiple masses. All tumors were subendocardial and involved the papillary muscles and/or cardiac valves. Two histologic patterns were recognized; both included giant cells. Pattern 1 was characterized by interlacing fascicles of spindle-shaped cells; pattern 2 resembled cavernous hemangioma. The 2 patterns coexisted and were linked by transitional zones. Given the immunohistochemical reactivity and ultrastructure, the spindle-shaped cells were identified as smooth muscle cells and the giant cells as endothelial cells. Single cell and multicellular angiogenesis by giant cells was observed. The tumors were classified as cardiac angioleiomyoma. Subendocardial multipotential mesenchymal cells, persistent tissue of the endocardial cushion, or valvular interstitial cells were suspected as the origin. PMID- 20574073 TI - Study on the infectivity of equine herpesvirus 9 (EHV-9) by different routes of inoculation in hamsters. AB - The infectivity and pathology of equine herpesvirus 9 (EHV-9), a new neurotropic equine herpesvirus isolated from gazelles, was studied in hamsters experimentally infected via nasal, ocular, oral, intravenous (IV), or peritoneal routes. Clinically, all animals inoculated by the nasal route and ~25% inoculated by the oral and peritoneal routes showed neurological signs on days 3, 6, and 9 postinoculation (PI), respectively. Neurological signs were not observed in animals administered EHV-9 by the IV and ocular routes. With the exception of animals administered EHV-9 by the IV route, all infected animals had lymphocytic meningoencephalitis. Although there were a number of differences in the severity and distribution of the lesions depending on the route of inoculation, the basic features of lymphocytic meningoencephalitis caused by EHV-9 were common. Lesions consisted of neuronal necrosis, perivascular aggregates of lymphocytes, plasma cells, and neutrophils, gliosis, intranuclear inclusion bodies, and diffuse lymphocytic infiltrates in the meninges. Viral antigen was detected in degenerated neurons in infected animals inoculated by the nasal, ocular, oral, and peritoneal routes. The distribution of EHV-9 antigen was somewhat dependent on inoculation route. There were no microscopic abnormalities or viral antigen in animals treated by the IV route. This study provides new data about experimental EHV-9 infection in hamsters through routes other than the IV route. These results suggest that in the animals infected by the oral, ocular, and peritoneal routes, EHV-9 might travel to the brain through nerves, other than by the olfactory route, after initial propagation at the site of viral entry. PMID- 20574074 TI - Evaluation of diuron (3-[3,4-dichlorophenyl]-1,1-dimethyl urea) in a two-stage mouse skin carcinogenesis assay. AB - Diuron (3-[3,4-dichlorophenyl]-1,1-dimethyl urea) is an herbicide with carcinogenic activity in rats and mice, which have developed respectively urothelial and mammary gland tumors in long-term studies. Accordingly, diuron has been categorized as a "likely human carcinogen" by the U.S. Environmental Protection Agency. Although the carcinogenesis-initiating activity of diuron has been reported in an early initiation-promotion mouse skin study, its genotoxic potential has been disputed. It is necessary to clarify the mode of action through which it has caused rodent neoplasia and verify its relevance to humans. Herein, two experiments were developed to verify the initiating and promoting potentials of diuron in a twenty-three- and a twenty-one-week-long mouse skin carcinogenesis protocol. In one, dimethylsulfoxide (DMSO) was the solvent for the herbicide; in the other, acetone was the alternative solvent in order to verify whether DMSO had inhibitory influence on a potential cutaneous carcinogenic activity. The adopted schedule for the tumor-promoting agent 12-O tetradecanoylphorbol 13-acetate (TPA) resulted in skin ulcers, which demonstrates the need for careful selection of TPA dose levels and frequency of application in this model. In both studies, diuron did not exert any influence on the skin carcinogenesis process, in contrast with results already reported in the literature. PMID- 20574075 TI - Time management for preclinical safety professionals. AB - A survey about time management in the workplace was distributed to obtain a sense of the level of job satisfaction among preclinical safety professionals in the current economic climate, and to encourage reflection upon how we manage time in our work environment. Roughly equal numbers of respondents (approximately 32%) identified themselves as management or staff, and approximately 27% indicated that they are consultants. Though 45.2% of respondents indicated that time management is very challenging for the profession in general, only 36.7% find it very challenging for themselves. Ten percent of respondents view time management to be exceedingly challenging for themselves. Approximately 34% of respondents indicated that prioritization of tasks was the most challenging aspect of time management for them. Focusing on an individual task was the second most challenging aspect (26%), followed equally by procrastination and delegation of tasks (12.4%). Almost equal numbers of respondents said that they would (35.2%) or might (33.3%) undertake training to improve their time management skills. Almost equal numbers of participants responded "perhaps" (44.6%) or "yes" (44.2%) to the question of whether management personnel should be trained in time management. PMID- 20574076 TI - Subcellular organelle lipidomics in TLR-4-activated macrophages. AB - Lipids orchestrate biological processes by acting remotely as signaling molecules or locally as membrane components that modulate protein function. Detailed insight into lipid function requires knowledge of the subcellular localization of individual lipids. We report an analysis of the subcellular lipidome of the mammalian macrophage, a cell type that plays key roles in inflammation, immune responses, and phagocytosis. Nuclei, mitochondria, endoplasmic reticulum (ER), plasmalemma, and cytoplasm were isolated from RAW 264.7 macrophages in basal and activated states. Subsequent lipidomic analyses of major membrane lipid categories identified 229 individual/isobaric species, including 163 glycerophospholipids, 48 sphingolipids, 13 sterols, and 5 prenols. Major subcellular compartments exhibited substantially divergent glycerophospholipid profiles. Activation of macrophages by the Toll-like receptor 4-specific lipopolysaccharide Kdo(2)-lipid A caused significant remodeling of the subcellular lipidome. Some changes in lipid composition occurred in all compartments (e.g., increases in the levels of ceramides and the cholesterol precursors desmosterol and lanosterol). Other changes were manifest in specific organelles. For example, oxidized sterols increased and unsaturated cardiolipins decreased in mitochondria, whereas unsaturated ether-linked phosphatidylethanolamines decreased in the ER. We speculate that these changes may reflect mitochondrial oxidative stress and the release of arachidonic acid from the ER in response to cell activation. PMID- 20574077 TI - Science to practice: photoacoustic imaging--can it let us see color and function deep inside the body? AB - Photoacoustic imaging imparts the ability to distinguish materials according to their differences in optical absorption (ie, their colors) with the high spatial and temporal resolution of ultrasonography (US). Experiments in rats demonstrate the advantages this approach would have in the clinically important application of percutaneous sentinel node biopsy. The incorporation of the technique in a conventional US imaging system gives promise of rapid translation to clinical use. PMID- 20574079 TI - Conflict of interest disclosure in RSNA journals: adoption of the International Council of Medical Journal Editors Uniform Format. PMID- 20574080 TI - Breast cancer screening: from science to recommendation. PMID- 20574081 TI - The 2009 U.S. Preventive Services Task Force guidelines ignore important scientific evidence and should be revised or withdrawn. PMID- 20574082 TI - Intravenous contrast medium-induced nephrotoxicity: is the medical risk really as great as we have come to believe? PMID- 20574083 TI - BI-RADS data should not be used to estimate ROC curves. PMID- 20574084 TI - Intravenous contrast medium administration and scan timing at CT: considerations and approaches. AB - The continuing advances in computed tomographic (CT) technology in the past decades have provided ongoing opportunities to improve CT image quality and clinical practice and discover new clinical CT imaging applications. New CT technology, however, has introduced new challenges in clinical radiology practice. One of the challenges is with intravenous contrast medium administration and scan timing. In this article, contrast medium pharmacokinetics and patient, contrast medium, and CT scanning factors associated with contrast enhancement and scan timing are presented and discussed. Published data from clinical studies of contrast medium and physiology are reviewed and interpreted. Computer simulation data are analyzed to provide an in-depth analysis of various factors associated with contrast enhancement and scan timing. On the basis of basic principles and analysis of the factors, clinical considerations and modifications to protocol design that are necessary to optimize contrast enhancement for common clinical CT applications are proposed. PMID- 20574085 TI - Diffusion-weighted imaging improves the diagnostic accuracy of conventional 3.0-T breast MR imaging. AB - PURPOSE: To evaluate the incremental value of diffusion-weighted (DW) imaging and apparent diffusion coefficient (ADC) mapping in relation to conventional breast magnetic resonance (MR) imaging in the characterization of benign versus malignant breast lesions at 3.0 T. MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by the institutional review board, with the requirement for informed patient consent waived. Of 550 consecutive patients who underwent bilateral breast MR imaging over a 10-month period, 93 women with 101 lesions met the following study inclusion criteria: They had undergone three dimensional (3D) high-spatial-resolution T1-weighted contrast material-enhanced MR imaging, dynamic contrast-enhanced MR imaging, and DW imaging examinations at 3.0 T and either had received a pathologic analysis-proven diagnosis (96 lesions) or had lesion stability confirmed at more than 2 years of follow-up (five lesions). DW images were acquired with b values of 0 and 600 sec/mm(2). Regions of interest were drawn on ADC maps of breast lesions and normal glandular tissue. Morphologic features (margin, enhancement pattern), dynamic contrast-enhanced MR results (semiquantitative kinetic curve data), absolute ADCs, and glandular tissue-normalized ADCs were included in multivariate models to predict a diagnosis of benign versus malignant lesion. RESULTS: Forty-one (44%) of the 93 patients were premenopausal, and 52 (56%) were postmenopausal. Thirty-three (32.7%) of the 101 lesions were benign, and 68 (67.3%) were malignant. Normalized ADCs were significantly different between the benign (mean ADC, 1.1 x 10(-3) mm(2)/sec +/- 0.4 [standard deviation]) and malignant (mean ADC, 0.55 x 10(-3) mm(2)/sec +/- 0.16) lesions (P < .001). Adding normalized ADCs to the 3D T1 weighted and dynamic contrast-enhanced MR data improved the diagnostic performance of MR imaging: The area under the receiver operating characteristic curve improved from 0.89 to 0.98, and the false-positive rate decreased from 36% (nine of 25 lesions) to 24% (six of 25 lesions). CONCLUSION: DW imaging with glandular tissue-normalized ADC assessment improves the characterization of breast lesions beyond the characterization achieved with conventional 3D T1 weighted and dynamic contrast-enhanced MR imaging at 3.0 T. PMID- 20574086 TI - Diabetes: prognostic value of CT coronary angiography--comparison with a nondiabetic population. AB - PURPOSE: To evaluate the prognostic value of multidetector computed tomographic (CT) coronary angiography in a diabetic population known to have or suspected of having coronary artery disease (CAD) compared with that in nondiabetic individuals. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. Three hundred thirteen patients with type 2 diabetes mellitus (DM) and 303 patients without DM underwent unenhanced 64 detector row CT, at which a calcium score was obtained, followed by CT angiography. Multidetector CT coronary angiograms were retrospectively classified as normal, showing nonobstructive CAD (50% luminal narrowing). During follow-up after CT angiography, major events (cardiac death, nonfatal myocardial infarction, and unstable angina requiring hospitalization) and total events (major events plus coronary revascularizations) were recorded for each patient. Cox proportional hazards analysis and Kaplan-Meier analysis were used to compare survival rates. RESULTS: In the group of 313 patients with DM, there were 213 men, and the mean age was 62 years +/- 11 (standard deviation). In the group of 303 patients without DM, there were 203 men, and the mean age was 63 years +/- 11. The mean number of diseased segments (5.6 vs 4.4, P = .001) and the rate of obstructive CAD (51% vs 37%, P < .001) were higher in patients with DM. Patients were followed up for a mean of 20 months +/- 5.4 (range, 6-44 months). At multivariate analysis, DM (P < .001) and evidence of obstructive CAD (P < .001) were independent predictors of outcome. Obstructive CAD remained a significant multivariate predictor for both patients with DM and patients without DM. In both patients with DM and patients without DM with absence of disease, the event rate was 0%. The event rate increased to 36% in patients without DM but with obstructive CAD and was highest (47%) in patients with DM and obstructive CAD. CONCLUSION: In both patients with DM and patients without DM, multidetector CT coronary angiography provides incremental prognostic information over baseline clinical variables, and the absence of atherosclerosis at CT coronary angiography is associated with an excellent prognosis. Multidetector CT coronary angiography might be a clinically useful tool for improving risk stratification in both patients with DM and patients without DM. PMID- 20574087 TI - Diagnostic accuracy of multidetector CT in acute mesenteric ischemia: systematic review and meta-analysis. AB - PURPOSE: To use meta-analysis to determine the diagnostic accuracy of contrast agent-enhanced multidetector computed tomography (CT) in primary acute mesenteric ischemia (AMI). MATERIALS AND METHODS: The PubMed search engine and five other electronic databases were searched for "mesenteric ischemia," "computed tomography," and related terms in articles published between January 1996 and September 2009, without language restrictions. Reference lists of retrieved articles were also searched. Two reviewers independently selected six studies that reported 2 x 2 contingency data on the diagnostic accuracy of multidetector CT in primary AMI in at least 10 patients with disease and 10 patients without disease and that used surgery or clinical outcome as the reference standard. Study data were independently extracted by the two reviewers, and disagreement was resolved by consensus. The study quality was assessed by using items from the Quality Assessment of Diagnostic Accuracy Studies tool. The primary 2 x 2 count data were investigated with a bivariate random-effects meta-analysis of sensitivity and specificity. RESULTS: Three studies were prospective, and three were retrospective. All studies were of high quality. The CT scanners used in the included studies had between four and 40 rows. The between-study heterogeneity was low to moderate. Overall, AMI was found in 142 of 619 studied cases. The meta analysis showed a pooled sensitivity of 93.3% (95% confidence interval: 82.8%, 97.6%) and a pooled specificity of 95.9% (95% confidence interval: 91.2%, 98.2%). CONCLUSION: On the basis of a thorough clinical examination, contrast-enhanced multidetector CT allows the diagnosis of primary AMI with high sensitivity and specificity. Thus, it may be used as the first-line imaging method. PMID- 20574088 TI - Sentinel lymph nodes in the rat: noninvasive photoacoustic and US imaging with a clinical US system. AB - PURPOSE: To evaluate in vivo sentinel lymph node (SLN) mapping by using photoacoustic and ultrasonographic (US) imaging with a modified clinical US imaging system. MATERIALS AND METHODS: Animal protocols were approved by the Animal Studies Committee. Methylene blue dye accumulation in axillary lymph nodes of seven healthy Sprague-Dawley rats was imaged by using a photoacoustic imaging system adapted from a clinical US imaging system. To investigate clinical translation, the imaging depth was extended up to 2.5 cm by adding chicken or turkey breast on top of the rat skin surface. Three-dimensional photoacoustic images were acquired by mechanically scanning the US transducer and light delivery fiber bundle along the elevational direction. RESULTS: Photoacoustic images of rat SLNs clearly help visualization of methylene blue accumulation, whereas coregistered photoacoustic/US images depict lymph node positions relative to surrounding anatomy. Twenty minutes following methylene blue injection, photoacoustic signals from SLN regions increased nearly 33-fold from baseline signals in preinjection images, and mean contrast between SLNs and background tissue was 76.0 +/- 23.7 (standard deviation). Methylene blue accumulation in SLNs was confirmed photoacoustically by using the optical absorption spectrum of the dye. Three-dimensional photoacoustic images demonstrate dynamic accumulation of methylene blue in SLNs after traveling through lymph vessels. CONCLUSION: In vivo photoacoustic and US mapping of SLNs was successfully demonstrated with a modified clinical US scanner. These results raise confidence that photoacoustic and US imaging can be used clinically for accurate, noninvasive imaging of SLNs for axillary lymph node staging in breast cancer patients. PMID- 20574089 TI - Characterization and correction of beam-hardening artifacts during dynamic volume CT assessment of myocardial perfusion. AB - PURPOSE: To fully characterize beam-hardening effects caused by iodinated contrast medium in the left ventricular (LV) cavity and aorta in the assessment of myocardial perfusion at computed tomography (CT) and to validate a beam hardening artifact correction algorithm that considers fluid-filled vessels and chambers important sources of beam hardening. MATERIALS AND METHODS: The Johns Hopkins University animal care and use committee approved all procedures. An anatomically correct LV and myocardial phantom to characterize beam-hardening artifacts was designed. Following validation in the phantom, the beam-hardening correction (BHC) algorithm was applied to 256-detector row dynamic volume CT images in a canine ischemia model (n = 5) during adenosine stress, and the effect of beam hardening was determined by comparing regional dynamic volume CT perfusion metrics (myocardial upslope normalized by maximum LV blood pool attenuation) with microsphere-derived myocardial blood flow (MBF). A paired Student t test was used to compare continuous variables from the same subject but under different conditions, while linear regression analysis was performed to estimate the slope and statistical significance of the relationship between CT derived perfusion metrics and microsphere-derived MBF. RESULTS: Beam-hardening artifacts were successfully reproduced in phantom studies and were eliminated with the BHC algorithm. The correlation coefficient of CT-derived perfusion metrics and microsphere-derived MBF improved from 0.60 to 0.74 (P > .05) following correction in the animal model. CONCLUSION: Beam-hardening artifacts confound dynamic volume CT assessment of myocardial perfusion. Application of the BHC algorithm is helpful for improving accuracy of myocardial perfusion at dynamic volume CT. PMID- 20574090 TI - Liver fibrosis in chronic hepatitis C virus infection: differentiating minimal from intermediate fibrosis with perfusion CT. AB - PURPOSE: To prospectively assess the utility of perfusion computed tomography (CT) for differentiating minimal from intermediate fibrosis in treatment-naive patients with chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS: This study was approved by the Institutional Review Board, and informed consent was obtained. Fifty-two patients with treatment-naive HCV infection underwent perfusion CT and percutaneous liver biopsy on the same day. Portal vein, arterial, and total liver perfusion; mean transit time; and distribution volumes for the right and left liver lobes were measured. Liver samples were scored for fibrosis, and fibrosis area was determined. Differences in quantitative perfusion parameters between patients with minimal fibrosis (score of F1) and those with intermediate fibrosis (score of F2 or F3) were tested. RESULTS: In patients with intermediate fibrosis (F2 and F3) compared with those with minimal fibrosis (F1), the portal venous perfusion (87 mL min(-1) 100 mL(-1) +/- 27 [standard deviation] vs 138 mL min(-1) 100 mL(-1) +/- 112, P = .042) and total liver perfusion (107 mL min(-1) 100 mL(-1) +/- 31 vs 169 mL min(-1) 100 mL(-1) +/- 137, P = .02) were significantly decreased, and the mean transit time was significantly increased (16 seconds +/- 4 vs 13 seconds +/- 5, P = .025). At multivariate analysis, only the mean transit time was an independent factor (odds ratio, 1.18; 95% confidence interval: 1.02, 1.37; P = .030). Receiver operating characteristic curve analysis showed that a mean transit time threshold of 13.4 seconds allowed discrimination between minimal and intermediate fibrosis with a sensitivity of 71% and a specificity of 65%. CONCLUSION: The results of this study show that perfusion changes occur early during fibrosis in chronic HCV infection and can be detected with perfusion CT. Perfusion CT may help to discriminate minimal from intermediate fibrosis. Mean transit time appears to be the most promising perfusion parameter for differentiating between fibrosis stages, although the large amount of overlap in the measured parameters limits the clinical utility of this test at present. PMID- 20574091 TI - Absence of tumor invasion into pelvic structures in locally recurrent rectal cancer: prediction with preoperative MR imaging. AB - PURPOSE: To retrospectively assess the accuracy of preoperative magnetic resonance (MR) imaging for identification of tumor invasion into pelvic structures in patients with locally recurrent rectal cancer scheduled to undergo curative resection. MATERIALS AND METHODS: The institutional review board approved this study, and informed consent was waived because of the retrospective nature of the study. Preoperative MR images in 40 consecutive patients with locally recurrent rectal cancer scheduled to undergo curative treatment between October 2003 and November 2006 were analyzed retrospectively. Four observers with different levels of experience in reading pelvic MR images assessed tumor invasion into the following structures: bladder, uterus or seminal vesicles, vagina or prostate, left and right pelvic walls, and sacrum. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and a receiver operating characteristic curve was constructed. Surgical and/or histopathologic findings were used as the reference standard. Interobserver agreement was measured by using kappa statistics. RESULTS: Preoperative MR imaging was accurate for the prediction of tumor invasion into structures with negative predictive values of 93%-100% and areas under receiver operating characteristic curves of 0.79-1.00 for all structures and observers. Positive predictive values were 53%-100%. Disease was overstaged in 11 (observer 1), 22 (observer 2), 10 (observer 3), and nine (observer 4) structures and was understaged in nine (observer 3) and two (observer 4) structures. Assessment failures were mainly because of misinterpretation of diffuse fibrosis, especially at the pelvic side walls. Interobserver agreement ranged between 0.64 and 0.99 for experienced observers. CONCLUSION: Preoperative MR imaging is accurate for the prediction of absence of tumor invasion into pelvic structures. MR imaging may be useful as a preoperative road map for surgical procedure and may thus increase chances of complete resection. Interpretation of diffuse fibrosis remains difficult. PMID- 20574092 TI - Distinguishing hypervascular pseudolesions of the liver from hypervascular hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging. AB - PURPOSE: To retrospectively determine findings at gadoxetic acid-enhanced magnetic resonance (MR) imaging in hypervascular pseudolesions that were observed at computed tomography (CT) during hepatic arteriography, with special focus on distinguishing these pseudolesions from hypervascular hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: The institute ethics committee deemed study approval unnecessary. The study population comprised 80 patients (55 men, 25 women) with chronic liver disease who underwent CT during hepatic arteriography and arterial portography, gadoxetic acid-enhanced MR imaging, and follow-up dynamic contrast material-enhanced CT. The diagnosis of 104 pseudolesions and 123 HCCs was confirmed by means of histopathologic or multimodality evaluation. Two radiologists assessed the MR imaging findings of HCCs and pseudolesions in consensus, including the signal intensities (SIs) of the lesions on T2-weighted, diffusion-weighted (DW), and contrast-enhanced hepatocyte-phase images. The findings of nodular pseudolesions and HCCs were compared with the Fisher exact test. Additionally, the hepatocyte-phase SI ratio (ratio of lesion SI to liver SI) for HCCs and pseudolesions was compared by means of the Mann-Whitney U test. RESULTS: There were 62 wedge-shaped, 32 nodular, and 10 linear pseudolesions. On gadoxetic acid-enhanced hepatocyte-phase MR images, 15% of pseudolesions (16 of 104) were hypointense compared with surrounding liver tissue. The mean hepatocyte phase SI ratio of HCCs (0.65 +/- 0.14 [standard deviation]) was significantly lower (P < .01) than that of the nodular pseudolesions (0.95 +/- 0.11). The optimal cutoff value of hepatocyte-phase SI ratio for distinguishing between HCC and nodular pseudolesion was 0.84. No nodular pseudolesions were visible on DW images. CONCLUSION: Gadoxetic acid-enhanced hepatocyte-phase MR imaging and DW imaging could be used to distinguish hypervascular pseudolesions from hypervascular HCCs; a hepatocyte-phase SI ratio below 0.84 and visibility on DW images were findings specific for HCCs rather than pseudolesions. PMID- 20574093 TI - Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. AB - PURPOSE: To compare the diagnostic performance of ultrasonography (US), computed tomography (CT), T1-weighted dual-echo magnetic resonance (MR) imaging, and point resolved proton (hydrogen 1[(1)H]) MR spectroscopy in the assessment of hepatic steatosis in patients undergoing liver resection. MATERIALS AND METHODS: This prospective study was approved by the institutional review board, and patients gave written informed consent. US, CT, T1-weighted MR imaging, and (1)H MR spectroscopy were performed preoperatively in 46 patients. Imaging results were correlated (Spearman correlation coefficient) with histopathologic analysis of results of intraoperative liver biopsies. To assess differences between groups, one-way analysis of variance was used. Sensitivity and specificity were calculated for each imaging modality by using receiver operating characteristic curve analysis, with a histopathologic cut-off value of 5% macrovesicular steatosis. Differences in sensitivity and specificity were assessed by means of McNemar analysis. RESULTS: At histopathologic examination, 23 patients had no (0% 5%) macrovesicular steatosis, 11 had mild (5%-33%), nine had moderate (33%-66%), and three had severe (>66%). MR imaging and (1)H MR spectroscopic measurements of hepatic fat had stronger correlation with histopathologic steatosis assessment (r = 0.85, P < .001 and r = 0.86, P < .001, respectively) than did US (r = 0.66, P < .001) and CT (r = -0.55, P < .001). Only T1-weighted MR imaging and (1)H MR spectroscopy showed differences across steatosis grades: none versus mild (P = .001 for both), mild versus moderate (P < .001 for both), and moderate versus severe (P = .04 and .01, respectively). Sensitivity of US, CT, T1-weighted MR imaging, and (1)H MR spectroscopy was 65% (13 of 20), 74% (17 of 23), 90% (19 of 21), and 91% (21 of 23), respectively, and specificity was 77% (17 of 23), 70% (14 of 20), 91% (20 of 22), and 87% (20 of 23), respectively. CONCLUSION: In contrast to US and CT, T1-weighted MR imaging and (1)H MR spectroscopy strongly correlate with histopathologic steatosis assessment and are able to demonstrate differences across steatosis grades. T1-weighted dual-echo MR imaging and (1)H MR spectroscopy had the best diagnostic accuracy in depicting hepatic steatosis. PMID- 20574094 TI - Findings of cecal volvulus at CT. AB - PURPOSE: To assess the diagnostic performance of computed tomographic (CT) and radiographic (as seen on CT topograms) signs of cecal volvulus. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant retrospective study, the CT and CT topogram findings in 11 patients (one man, 10 women; age range, 26-100 years) with surgically confirmed cecal volvulus and 12 control patients were reviewed. The control subjects had suspicious radiographs, had undergone CT within 24 hours of radiography, and had received a clinical diagnosis other than cecal volvulus. Three radiologists independently evaluated the CT topograms for cecal distention, the coffee bean sign, cecal apex location, and distal colon decompression. CT images were analyzed for cecal distention, cecal apex location, distal colon decompression, and presence or absence of the whirl, ileocecal twist, transition point(s), the X-marks-the-spot, and the split wall. Sensitivity, specificity, and predictive values were computed. Baseline statistical values for the cecal volvulus and control groups were analyzed by using a two-tailed Z test to compare proportions with a threshold confidence interval of 95%. CT findings of bowel ischemia (free air or fluid, pneumatosis intestinalis, portal venous gas, mesenteric stranding) were correlated with pathology report findings. RESULTS: On CT topograms, greater than 10-cm cecal distention, coffee bean sign, and left upper quadrant cecal apex had sensitivities of 45% (five of 11 patients), 27% (three of 11 patients), and 45% (five of 11 patients), respectively, and specificities of 100% (12 of 12 control subjects), 92% (11 of 12 control subjects), and 100% (12 of 12 control subjects), respectively. Distal colon decompression had sensitivities and specificities of 91% (10 of 11 patients) and 83% (10 of 12 control subject), respectively, on topograms and of 91% (10 of 11 patients) and 92% (11 of 12 patients), respectively, on CT images. On cross-sectional CT images, greater than 10-cm cecal distention, left upper quadrant cecal apex, whirl, ileocecal twist, transition point(s), X-marks-the-spot, and split wall had sensitivities of 45% (five of 11 patients), 36% (four of 11 patients), 73% (eight of 11 patients), 54% (six of 11 patients), 82% (nine of 11 patients), 27% (three of 11 patients), and 54% (six of 11 patients), respectively; each had 100% specificity. Pneumatosis intestinalis and free air had 100% (four of four control subjects) specificity. Overall, CT signs of bowel ischemia correlated poorly with pathology report findings. CONCLUSION: When cecal volvulus is suspected, the absence of distal colonic decompression on CT topograms makes the diagnosis very unlikely. Whirl, ileocecal twist, transition points, X-marks-the-spot, and split wall have high specificity for cecal volvulus. PMID- 20574096 TI - Temporomandibular joint findings in adults with long-standing juvenile idiopathic arthritis: CT and MR imaging assessment. AB - PURPOSE: To assess the long-term temporomandibular joint (TMJ) manifestations of juvenile idiopathic arthritis (JIA), as depicted at computed tomography (CT) and magnetic resonance (MR) imaging, in 47 adult patients. MATERIALS AND METHODS: The study was approved by a regional committee for medical research ethics, and informed consent was obtained from all patients. Forty-seven patients with JIA (32 women, 15 men; mean age, 35 years) were examined, on average, 30 years after the initial diagnosis. The findings of TMJ imaging, including CT and MR imaging, were evaluated by three observers. Bone and disk abnormalities, joint effusion, bone marrow abnormalities, and contrast enhancement were analyzed. RESULTS: The TMJs were involved in 33 (70%) of the 47 patients with JIA, with bilateral involvement in 29 patients. Slight to moderate contrast enhancement was observed on the images obtained in 14 (42%) of the 33 patients with TMJ JIA abnormalities. All main joint components were abnormal in 28 of the 33 patients, mainly showing flat deformed condyles, wide flat fossae, and thin or perforated disks in the normal position, or absent disks. Condylar concavity or bifidity, and secondary osteoarthritis were found in approximately half of the abnormal joints. CONCLUSION: Long-term JIA manifestations in the TMJs, as demonstrated at CT and MR imaging, were frequent, usually bilateral, and characterized by mandibular condyle and temporal bone deformities, abnormal disk morphology, and, rather frequently, osteoarthritis and mild synovitis. PMID- 20574095 TI - Detectability of urinary stones on virtual nonenhanced images generated at pyelographic-phase dual-energy CT. AB - PURPOSE: To evaluate the detectability of urinary stones on virtual nonenhanced images generated at pyelographic-phase dual-energy computed tomography (CT). MATERIALS AND METHODS: This retrospective HIPAA-compliant study was institutional review board approved. All included patients had previously consented to the use of their medical records for research. Sixty-two patients (38 men, 24 women; age range, 35-91 years) had undergone CT urography, which consisted of nonenhanced and pyelographic-phase dual-energy CT performed by using a dual-source scanner. Commercial software was used to create virtual nonenhanced images by suppressing the iodine signal from the pyelographic-phase dual-energy CT scans. Two radiologists, in consensus, evaluated the virtual nonenhanced images for the presence of stones. Sensitivity for detecting stones was calculated on a per stone basis. Sensitivity, specificity, and accuracy were also calculated on a per renal unit (defined as the intrarenal collecting system and ureter of one kidney) basis. The true nonenhanced scan was considered the reference standard. A jackknife method was used because any patient may have multiple stones. RESULTS: Of 62 patients with 122 renal units, 21 patients with 25 renal units had a total of 43 stones (maximal transverse diameter range, 1-24 mm; median, 3 mm). The overall sensitivity for detecting stones was 63% (27 of 43 stones) per stone. Sensitivities were 29% (four of 14 stones) for 1-2-mm stones, 64% (nine of 14 stones) for 3-4-mm stones, 83% (five of six stones) for 5-6-mm stones, and 100% (nine of nine stones) for 7-mm or larger (7, 7, 7, 8, 8, 9, 11, 15, and 24 mm) stones. All three ureteral stones (3, 4, and 8 mm) were correctly identified. The sensitivity, specificity, and accuracy for detecting stones on a per-renal unit basis were 65% (17 of 26 renal units), 92% (88 of 96 renal units), and 86% (105 of 122 renal units), respectively. CONCLUSION: Virtual nonenhanced images generated at pyelographic-phase dual-energy CT enabled the detection of urinary stones with moderate accuracy. The detection of small (1-2-mm) stones was limited. PMID- 20574097 TI - Symptomatic carotid artery stenosis: impairment of cerebral autoregulation measured at the brain tissue level with arterial spin-labeling MR imaging. AB - PURPOSE: To measure the cerebral autoregulatory status of the brain tissue supplied by the individual brain-feeding arteries in patients with symptomatic stenosis of the internal carotid artery (ICA) by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging and to compare this status with that in healthy controls. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-three patients (mean age, 69.3 years +/- 8.0 [standard deviation]) with unilateral symptomatic stenosis of the ICA and 20 healthy controls (mean age, 66.8 years +/- 6.3 [standard deviation]) underwent perfusion and flow territory-selective ASL MR imaging before and after intravenous administration of acetazolamide. Cerebrovascular reactivity was measured throughout the brain in the gray matter that is supplied by the individual ICAs and the basilar artery. Data were analyzed with paired and unpaired t tests. RESULTS: In patients with symptomatic stenosis of the ICA, the flow territory of the symptomatic ICA was smaller than that of the asymptomatic ICA. After administration of acetazolamide, a significant increase in cerebral blood flow at the brain tissue level was measured in both control subjects and patients in all perfusion territories. Mean cerebrovascular reactivity values were 35.9% +/- 3.0% (standard error) and 44.6% +/- 3.5% (standard error) in the flow territories of the patients with symptomatic ICAs and those with asymptomatic ICAs, respectively, and 47.9% +/- 3.1% (standard error) in the control subjects. Cerebrovascular reactivity was lower in the flow territory of the symptomatic ICA than in the arteries of control participants (mean difference, -12.0%; 95% confidence interval: -20.7%, -3.3%). CONCLUSION: In patients with symptomatic stenosis of the ICA, vasodilatory capacity in the flow territories of the major cerebral arteries can be visualized and quantified at the brain tissue level with ASL MR imaging. PMID- 20574098 TI - Intracranial dural arteriovenous fistulas: diagnosis and evaluation with 64 detector row CT angiography. AB - PURPOSE: To analyze the diagnostic effectiveness and application of computed tomographic (CT) angiography by using a new algorithm (hybrid CT angiography) in dural arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Institutional review board approval was obtained for retrospectively postprocessing the raw data from CT angiography by using hybrid CT, which is a mixture of a bone subtraction and masking method for bone removal. The study included 22 patients with 24 dural AVFs and 14 control subjects. The grades in patients with dural AVF determined with hybrid CT angiography and digital subtraction angiography (DSA) were compared, and hybrid CT angiography was applied as a tool for planning endovascular treatment. The adjusted Wald method was used to estimate confidence intervals (CIs), and the Cohen kappa statistic was used to assess interobserver agreement. RESULTS: Hybrid CT angiography in the 24 dural AVFs revealed asymmetric sinus enhancement in 22 lesions (92%), engorged arteries in 19 (79%), transosseous enhanced vessels in 19 (79%), engorged extracranial veins in 13 (54%), engorged cortical veins in seven (29%), and sinus thrombosis in four (17%). In all 24 lesions, at least two of six imaging signs for diagnosis of dural AVFs were present. The kappa test analysis revealed a high level of interobserver agreement (kappa, 0.56-1.00) in reading the diagnostic imaging signs. The observed agreement between DSA and readers was 100% in the cavernous sinus region and in hypoglossal and clival lesions and 78%-89% in the transverse sigmoid sinus. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 0.93 (95% CI: 0.85, 0.97), 0.98 (95% CI: 0.93, 1.00), 0.97 (95% CI: 0.90, 0.99), and 0.95 (95% CI: 0.90, 0.98), respectively. CONCLUSION: Hybrid CT angiography is a promising tool for the diagnosis of dural AVF. It can provide key information necessary for treatment planning. PMID- 20574099 TI - Diffuse lung disease: CT of the chest with adaptive statistical iterative reconstruction technique. AB - PURPOSE: To compare visualization of subtle normal and abnormal findings at computed tomography (CT) of the chest for diffuse lung disease with images reconstructed with filtered back projection and adaptive statistical iterative reconstruction (ASIR) techniques. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board-approved study, 24 patients underwent 64-section multi detector row CT of the chest for evaluation of diffuse lung disease. Scanning parameters included a pitch of 0.984:1 and 120 kVp in thin-section mode, with 2496 views per rotation compared with 984 views acquired for normal mode. The 0.625-mm-thick images were reconstructed with filtered back projection, ASIR, and ASIR high-definition (ASIR-HD) kernels. Two thoracic radiologists independently assessed the filtered back projection, ASIR, and ASIR-HD images for small anatomic details (interlobular septa, centrilobular region, and small bronchi and bronchioles), abnormal findings (reticulation, tiny nodules, altered attenuation, bronchiectasis), image quality (graded by using a six-point scale, where 1 = excellent image quality, and 5 = interpretation impossible), image noise, and artifacts. Data were tabulated for statistical testing. RESULTS: For visualization of normal and pathologic structures, CT image series reconstructed with ASIR-HD were rated substantially better than those reconstructed with filtered back projection and ASIR (P < .001). ASIR-HD images were superior to filtered back projection images in 15 of 24 (62%) patients for visualization of normal structures and in 24 of 24 (100%) patients for pathologic findings. ASIR HD was superior to ASIR in three of 24 (12%) images for normal anatomic findings and in seven of 24 (29%) images for pathologic evaluation. None of the images in the three groups were rated as unacceptable for noise (P < .001). CONCLUSION: ASIR-HD reconstruction results in superior visualization of subtle and tiny anatomic structures and lesions in diffuse lung disease compared with ASIR and filtered back projection reconstructions. PMID- 20574101 TI - Chronic obstructive pulmonary disease: longitudinal hyperpolarized (3)He MR imaging. AB - PURPOSE: To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. MATERIALS AND METHODS: All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and age range) at baseline and 26 months +/- 2 (standard deviation) later. Apparent diffusion coefficients (ADCs) derived from (3)He MR imaging were calculated from diffusion-weighted (3)He MR images, and (3)He ventilation defect volume (VDV) and ventilation defect percentage (VDP) were generated after manual segmentation of (3)He MR spin-density images. RESULTS: For subjects with COPD, significant increases in (3)He MR imaging-derived VDV (P = .03), VDP (P = .006), and ADC (P = .02) were detected, whereas there was no significant change in forced expiratory volume in 1 second (FEV(1)) (P = .97). For healthy never-smokers, there was no significant change in imaging or pulmonary function measurements at follow-up. There was a significant correlation between changes in FEV(1) and changes in VDV (r = -0.70, P = .02) and VDP (r = -0.70, P = .03). CONCLUSION: For this small pilot group of ex-smokers with COPD, (3)He MR imaging-derived VDV, VDP, and ADC measurements worsened significantly, but there was no significant change in FEV(1), suggesting increased sensitivity of hyperpolarized (3)He MR imaging for depicting COPD changes during short time periods. PMID- 20574100 TI - Unenhanced dynamic MR angiography: high spatial and temporal resolution by using true FISP-based spin tagging with alternating radiofrequency. AB - PURPOSE: To present an unenhanced four-dimensional time-resolved dynamic magnetic resonance (MR) angiography technique with true fast imaging with steady-state precession-based spin tagging with alternating radiofrequency (STAR), also called TrueSTAR. MATERIALS AND METHODS: This study received Institutional Review Board approval and was HIPAA compliant. Informed consent was obtained from all study subjects. In eight healthy volunteers, the spatial and temporal resolution of the TrueSTAR technique were optimized. In another six healthy volunteers, the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) of the TrueSTAR dynamic MR angiography images were compared with those acquired by using a standard Look-Locker echo-planar technique by using the Wilcoxon signed rank test. Finally, one patient with an arteriovenous malformation (AVM) was studied by using this technique. RESULTS: The SNR and CNR of the TrueSTAR dynamic MR angiography images were 29% and 39% higher, respectively, compared with those acquired by using a standard Look-Locker echo-planar imaging sequence (both P = .028). In the AVM patient, TrueSTAR dynamic MR angiography delineated the dynamic course of labeled blood flowing through feeding arteries into the nidus and draining veins. CONCLUSION: The results suggest that TrueSTAR is a promising unenhanced dynamic MR angiography technique for clinical evaluation of cerebrovascular disorders such as AVM, steno-occlusive disease, and aneurysm. PMID- 20574102 TI - US-guided renal transplant biopsy: efficacy of a cortical tangential approach. AB - PURPOSE: To describe the cortical tangential approach to ultrasonographically (US) guided renal transplant biopsy and evaluate its efficacy in obtaining sufficient cortical tissue. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was exempted from review by the institutional review board. Informed consent was not required. The number of core biopsy samples, glomeruli, and small arteries obtained during 294 consecutive US-guided renal transplant biopsies in 254 patients (134 men, 120 women; age range, 19-79 years; mean age, 52.2 years) in one department between June 1 and December 31, 2008, were recorded, along with any ensuing complications. Procedural success was assessed according to Banff 97 criteria. RESULTS: There were 1.2 +/- 0.4 (standard deviation) biopsy core samples taken per case by 11 radiologists using the cortical tangential approach. In 290 cases, biopsy results showed 21.7 +/- 10.1 glomeruli and 5.0 +/- 2.8 small arteries. Two hundred seventy-six (95%) cases were adequate or minimal according to Banff 97 assessment criteria. Of the 14 inadequate cases (5%), six were lacking only one glomerulus to achieve minimal status. Only one biopsy core sample was taken in all 14 inadequate cases and in 233 successful cases (success rate, 85%). None of the 43 cases with two or more biopsy core samples taken were inadequate (success rate, 100%). Two patients (0.7%) had a hemorrhagic complication requiring transfusion, and another four patients (1.4%) experienced a minor self-limiting complication. CONCLUSION: The cortical tangential approach can be used by a cohort of radiologists to achieve 95% or higher collective success in obtaining cortical tissue during renal transplant biopsy, with few complications. The success rate is higher, without increased complications, when more than one core specimen is taken. PMID- 20574103 TI - Abdominal masses sampled at PET/CT-guided percutaneous biopsy: initial experience with registration of prior PET/CT images. AB - PURPOSE: To establish the feasibility of performing combined positron emission tomography (PET)/computed tomography (CT)-guided biopsy of abdominal masses by using previously acquired PET/CT images registered with intraprocedural CT images. MATERIALS AND METHODS: In this HIPAA-compliant institutional review board approved study, 14 patients underwent clinically indicated percutaneous biopsy of abdominal masses (mean size, 3.3 cm; range, 1.2-5.0 cm) in the liver (n = 6), presacral soft tissue (n = 3), retroperitoneal lymph nodes (n = 2), spleen (n = 2), and pancreas (n = 1). PET/CT images obtained no more than 62 days (mean, 18.3 days) before the biopsy procedure were registered with intraprocedural CT images by using image registration software. The registered images were used to plan the procedure and help target the masses. RESULTS: The image registrations were technically successful in all but one patient, who had severe scoliosis. The remaining 13 biopsy procedures yielded diagnostic results, which were positive for malignancy in 10 cases and negative in three cases. CONCLUSION: PET/CT-guided abdominal biopsy with use of prior PET/CT images registered with intraprocedural CT scans is feasible and may be helpful when fluorine 18 fluorodeoxyglucose-avid masses that are not seen sufficiently with nonenhanced CT are sampled at biopsy. PMID- 20574104 TI - Triple-lumen peripherally inserted central catheter in patients in the critical care unit: prospective evaluation. AB - PURPOSE: To prospectively evaluate outcomes associated with use of a triple-lumen (TL) peripherally inserted central catheter (PICC) in the intensive care unit (ICU) setting. MATERIALS AND METHODS: Patients were prospectively enrolled in this HIPAA-compliant, institutional review board-approved study. Informed consent was obtained. All patients were in one hospital's ICUs and needed intermediate term central venous access requiring three lumina. A 6-F tapered TL PICC was placed by a bedside nursing-based team with backup from the Interventional Radiology department. Placement complications, as well as long-term complications, were recorded. At catheter removal, ultrasonography (US) of the veins containing the TL PICC was performed to detect occult venous thrombosis. Regardless of indication for removal, catheters were sent for culture to detect colonization. RESULTS: The study was stopped prematurely after 50 of a planned 167 patients were enrolled when a scheduled interim analysis detected a venous thrombosis rate that was considered unacceptably high by the study oversight committee (thrombosis was symptomatic in 20% of patients [10 of 50]). Venous thrombosis (symptomatic or asymptomatic) was detected in 26 of 45 patients (58%; 95% confidence interval [CI]: 43%, 72%) examined with US. Documented catheter related bloodstream infection did not occur (0%; 95% CI: 0%, 7%); colonization was detected in three of 29 catheter tips sent for culture (10%; 95% CI: 2%, 27%). Catheter malfunction and dislodgment occurred in one patient each. CONCLUSION: The TL PICC design used in this study resulted in unacceptably high venous thrombosis rates. Even when used in a high-risk setting for infection (ie, the ICU), rates of clinically evident infection and colonization were absent and low, respectively. PMID- 20574106 TI - Case 159: cerebral amyloid angiopathy-related inflammation. PMID- 20574107 TI - Claustrophobia preventing MR imaging of the breast. PMID- 20574108 TI - Improved language performance in Alzheimer disease following brain stimulation. AB - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for the cognitive deficits associated with Alzheimer disease (AD). The aim of this study was to assess the long-term effects, on cognitive performance, of rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) in AD patients. METHODS: Ten AD patients were randomly assigned to one of two study groups. Multiple-baseline design was used.The first group underwent a 4 week real rTMS stimulation protocol, while the second underwent a 2-week placebo treatment, followed by 2 weeks of real rTMS stimulation. Each session consisted of the application of rhythmic high-frequency rTMS over the DLPFC for 25 min. Sessions occurred once daily, 5 days/week. The main analysed outcome was the change in cognitive test performance at 2 and 4 weeks after rTMS treatment initiation, with a follow-up performed 8 weeks after the end of rTMS, in comparison with baseline performance. RESULTS: A significant difference was found between groups over sessions in terms of the percentage of correct responses of auditory sentence comprehension. Only real treatment induced an improvement in performance with respect to baseline or placebo. Moreover, both groups showed a lasting effect on the improved performance 8 weeks after the end of treatment. CONCLUSION: The findings provide initial evidence for the persistent beneficial effects of rTMS on sentence comprehension in AD patients. Rhythmic rTMS, in conjunction with other therapeutic interventions, may represent a novel approach to the treatment of language dysfunction in AD patients. PMID- 20574109 TI - Paternal smoking and breastfeeding in Xinjiang, PR China. AB - A cohort of 1088 couples in Xinjiang, PR China, were recruited to study infant feeding practices and paternal smoking. Mothers were interviewed in hospital and at 0.5, 1.5, 2.5, 3.5, 4.5, and 6 months. Survival analysis was used to calculate breastfeeding rates in smokers and nonsmokers. The paternal smoking rate was 64.8% and maternal smoking rate 1.7% (P < .01). The rates for any breastfeeding in the smoking group were significantly lower than in the nonsmoking group from 3.5 months to 6 months (P < .05). The rates for exclusive breastfeeding in the paternal smoking group were lower than in the nonsmoking group from discharge to 6 months (P < .05). The median duration of exclusive breastfeeding in the paternal smoking group was shorter than in the nonsmoking group. Paternal smoking was a risk factor for stopping any breastfeeding (hazard risk, 1.84; 95% confidence interval, 1.11-3.04) and exclusive breastfeeding (hazard risk, 1.33; 95% CI, 1.09-1.64) compared with nonsmokers. PMID- 20574119 TI - Medicinal plants as immunosuppressive agents in traditional Iranian medicine. AB - Immunomodulation using medicinal plants provides an alternative to conventional chemotherapy for several diseases, especially when suppression of inflammation is desired. The "Canon of Medicine", the epochal work of Avicenna, the great Persian scientist of the middle ages, provides comprehensive information about medicinal plants which used to cure inflammatory illnesses in traditional Iranian medicine. Taking into consideration that the mechanisms of damage in these illnesses are mediated by immune responses, it is reasonable to assume that the plants used for such diseases may suppress the immune responses and the resultant inflammation. In Iran, because of great diversity of climate and geographical conditions, numerous varieties of plants grow and at least 1000 species are recorded as medicinal plants. Many of these plants such as Punica granatum, Glycyrrhiza glabra, Foeniculum vulgare and Polygonum species prescribed by ancient Iranian physicians have been shown to possess anti-inflammatory and immunomodulatory effects. In recent literature, different species of native medicinal plants such as Stachys obtusicrena, Salvia mirzayanii, Echium amoenum, Dracocephalum kotschyi and Linum persicum have been shown to have appreciable anti-inflammatory and immunomodulatory effects including inhibitory effects on lymphocyte activation, suppression of cellular and humoral immunity and induction of apoptosis. This review focuses on plants that are used in Iranian traditional medicine and have been reported to act as immunoinhibitory agents. PMID- 20574110 TI - SR proteins and galectins: what's in a name? AB - Although members of the serine (S)- and arginine (R)-rich splicing factor family (SR proteins) were initially purified on the basis of their splicing activity in the nucleus, there is recent documentation that they exhibit carbohydrate-binding activity at the cell surface. In contrast, galectins were isolated on the basis of their saccharide-binding activity and cell surface localization. Surprisingly, however, two members (galectin-1 and galectin-3) can be found in association with nuclear ribonucleoprotein complexes including the spliceosome and, using a cell free assay, have been shown to be required splicing factors. Thus, despite the difference in terms of their original points of interest, it now appears that members of the two protein families share four key properties: (a) nuclear and cytoplasmic distribution; (b) pre-mRNA splicing activity; (c) carbohydrate binding activity; and (d) cell surface localization in specific cells. These findings provoke stimulating questions regarding the relationship between splicing factors in the nucleus and carbohydrate-binding proteins at the cell surface. PMID- 20574120 TI - In vivo effects of calcitriol on phenotypic and functional properties of dendritic cells. AB - BACKGROUND: Dendritic cells (DCs) play a central role in the initiation and expansion of T cell mediated immune responses with potential immunotherapy application. The compounds which have the ability to induce immunomodulatory effects on DCs may be employed for the treatment of immunopathologic conditions such as autoimmune diseases. OBJECTIVE: The aim of this study was to investigate the in vivo effects of calcitriol (active form of vitamin D3) on DCs. METHODS: 0.1 microgram calcitriol was injected intra-peritoneally into C57BL/6 mice every other day within 3 weeks, and spleen DCs were extracted by magnetic beads. The phenotypic and functional properties of DCs were studied by flow cytometry and mixed lymphocyte reaction (MLR), respectively. RESULTS: The expression of CD86 and MHC II, as maturation markers and costimulatory molecules were significantly decreased (p=0.028 and p=0.047, respectively) while CD11b expression, as a marker of mice myeloid DCs which mostly induces Th2 cytokine profile, was significantly increased (p=0.011). Allogeneic T cell stimulation in MLR was also significantly inhibited in comparison with the control groups (p<0.05). CONCLUSION: Our data indicate that in vivo calcitriol administration inhibits maturation and activation of DCs in the same manner as in vitro conditions. PMID- 20574121 TI - Comparison of several maturation inducing factors in dendritic cell differentiation. AB - BACKGROUND: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. OBJECTIVE: In this study, we compared tumor necrosis factor-alpha, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. METHODS: We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-alpha, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. RESULTS: Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells generated by TNF-alpha, CpG, Poly I:C, and LPS treatment of the immature dendritic cells. However, a significantly poorer proliferation of lymphocytes cocultured with the Poly I:C-treated DCs was observed compared to the CpG-treated DCs in mixed leukocyte reaction (p=0.026). Conversely, a significantly stronger proliferation of lymphocytes was observed when cocultured with TNF-alpha-treated DCs compared to the LPS-treated DCs (p=0.025). CONCLUSION: Our results indicated that all of studied maturation inducing factors can be used in DC maturation but TNF-alpha and CpG were the preferred in vitro maturation factors. It is concluded that maturation of dendritic cells by CpG motif and TNF-alpha can be used to regulate immune responses. PMID- 20574122 TI - Inhibitory killer cell immunoglobulin-like receptor KIR3DL1 in combination with HLA-B Bw4iso protect against ankylosing spondylitis. AB - BACKGROUND: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). OBJECTIVE: We investigated the HLA-C and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing Spondylitis (AS) susceptibility, alone or in combination. METHODS: We typed 40 AS patients and 40 normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-B Bw4(thero), HLA-B Bw4(iso) and HLA-A Bw4 alleles by PCR SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis. RESULTS: The frequency of HLA-B Bw4(iso) but not HLA-B Bw4(thero) and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-B(iso) gene was reduced in patients with AS compared to healthy controls (p<0.009). CONCLUSION: We conclude that HLA-B Bw4(iso), the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease. PMID- 20574123 TI - IL-1beta (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms in H. pylori mediated gastric disorders. AB - BACKGROUND: Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection. OBJECTIVE: The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population. METHODS: One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori (control group) were studied for the association between IL-1beta (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylori-mediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP PCR. RESULTS: Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H. pylori(+) non ulcerative gastritis(+), H. pylori(+) ulcerative gastritis(+) and H. pylori(-) non-ulcerative gastritis(+). A significantly higher frequency of TT genotype (p=0.02) in IL-1beta +3953 in H. pylori(+) ulcerative gastritis(+) was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 (-251A/T) were found among the patients. CONCLUSION: The data suggest that TT genotype in IL-1beta +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations. PMID- 20574124 TI - Association of interleukin-4 and IgE levels with LDL oxidation in atherosclerosis. AB - BACKGROUND: Atherosclerosis is an inflammatory and multifactorial disease, with a high prevalence rate in Pakistan. OBJECTIVE: To find a relation between serum IL 4 and IgE levels with oxidized LDL in atherosclerosis. METHODS: In this observational, cross sectional study 99 male patients, between forty and sixty years of age, with a history of ischemic heart disease (IHD) and established atherosclerotic plaques on angiography were recruited. The study was completed within three years (Jan 2007 to Jan 2009). One hundred and one age and gender matched healthy subjects with no known history of IHD were also recruited. All the study participants were non-diabetics. Serum IL-4, IgE and oxidized LDL (ox LDL) levels were measured by quantitative ELISA technique. RESULTS: Serum IL-4 levels were generally undetectable or very low, but were higher in the patient group compared to the control subjects. Similarly, oxidized LDL and serum IgE levels were also increased in the patient group compared to the control, but the differences were not statistically significant. CONCLUSION: Our study could not detect any relationship between IL-4 and IgE levels with LDL oxidation in atherosclerosis. PMID- 20574125 TI - Comparison of immunoblotting and ELISA for detection of anti-ganglioside antibodies in children with Guillain-Barre syndrome. AB - BACKGROUND: Anti-ganglioside antibody assays are widely used for diagnosis of autoimmune peripheral neuropathies. OBJECTIVE: This study aimed to determine serum levels of anti-ganglioside antibodies in children with Guillain-Barre syndrome by immunoblotting technique and compare the results with those obtained by ELISA method. METHOD: In this investigation, 50 children with Guillain-Barre syndrome (GBS) who were admitted from July 2006 to July 2008, to Tabriz Children's Hospital in the northwest of Iran were studied. 30 children admitted for various other reasons than GBS were randomly selected as a control group. The levels of anti-ganglioside antibodies in serum were measured by ELISA and immunoblotting methods using commercial kits. RESULTS: Anti-ganglioside antibodies (IgG) were detected in 16 (32%) GBS patients and in 1 (3.3%) control using ELISA assay. However, by employing immunoblotting technique, antibodies against seven gangliosides were found positive in 28 (56%) of GBS patients and none in the control group. The sensitivities of immunoblotting and ELISA methods were 56% and 32% and their specificities were 100% and 97%, respectively (p<0.001). CONCLUSION: According to the clinical criteria of GBS, the specificity and sensitivity of immunoblotting was better than those of ELISA. It is important to notice that the immunoblotting method is able to measure the seven types of antibodies (GM1, GM2, GM3, GD1a, GD1b, GT1b, and GQ1b) simultaneously and it is an easy, routine method with a lower cost. PMID- 20574126 TI - Pro-inflammatory cytokines in Omani type 2 diabetic patients presenting anxiety and depression. AB - BACKGROUND: The relationship of inflammatory cytokines with anxiety and depression has been reported, but their role in diabetic patients has not been fully elucidated. OBJECTIVE: We examined whether an association between prevalence of anxiety and depression in Omani type-2 diabetic patients (n=30) and the levels of inflammatory markers such as IL-1beta, TNF-alpha, IFN-gamma and C reactive protein (CRP) exists. METHODS: Symptoms of anxiety and depression were screened using the Hospital Anxiety and Depression Scale (HADS) through self rated questionnaires. IL-1beta, TNF-alpha, IFN-gamma, CRP, anti-TPO and anti GAD65 antibodies were measured in patients' sera using commercially available ELISA assays. RESULTS: In Omani type-2 diabetic patients, high prevalence of anxiety and depression along with high levels of inflammatory markers were detected. However, no correlation was observed between inflammatory markers and anxiety or depression. CONCLUSION: These results indicate that Omani type-2 diabetic patients are at great risk for developing anxiety and depression. Therefore, these complications need more care and attention. There was no association between scores of anxiety and depression with the levels of inflammatory cytokines. This may need to be elucidated in a larger cohort of patients. PMID- 20574127 TI - 2009 H1N1 influenza virus seroepidemiology. PMID- 20574128 TI - Three-dimensional observation of decrease in pulp cavity volume using micro-CT: age-related change. AB - We investigated three-dimensional decrease in the volume of the pulp chamber caused by age-related secondary dentin formation using micro-CT and evaluated the applicability of the results to evaluation of age taking into account sex, age and tooth type. Decrease was slightly higher in females than in males, and a higher correlation between decrease and aging was observed in females. A comparison between age-groups revealed that decrease progressed between the fifties and sixties in males, and the forties and fifties in females. A stronger correlation between aging and decrease was observed in the mandibular central incisors than in the mandibular second premolars. This correlation was higher than other correlations between sexes and age-groups. PMID- 20574129 TI - Corrosion properties of Ag-Au-Cu-Pd system alloys containing indium. AB - In this study, the corrosion resistance of Ag-Au-Cu-Pd system alloys consisting of 5 or 10 mass% indium was evaluated. Levels of element release and tarnish were determined and electrochemical measurements performed. Results were compared with those for commercial silver-palladium-gold alloy. In terms of electrochemical behavior, the transpassive potential of these experimental alloys was 168-248mV. Experimental alloys with 25 mass% Au showed similar corrosion resistance to control gold-silver-palladium alloy. Amount of released elements was 14 130microg/cm(2) at 7 days, which is in the allowable range for dental alloys. Addition of indium to Ag-Au-Cu-10mass%Pd system alloys was effective in increasing resistance to tarnish and alloys containing 10 mass% of indium showed a minimal decrease in L(*) values after immersion. These findings indicate that 25Au-37.5Ag-15Cu-10Pd-2Zn-10In-0.5Ir alloy is applicable in dental practice. PMID- 20574130 TI - Dental-care utilization patterns and factors associated with regular dental check ups in elderly. AB - The purpose of this study was to investigate dental care utilization patterns in the elderly and to evaluate factors associated with regular dental check-ups in this age group. A total of 211 elderly people (50 men, 161 women) aged between 60 and 98 years were investigated. A cross-sectional survey by questionnaire was carried out on visitors to the Mihama Ikiiki Plaza (an institution for the elderly) in the city of Chiba, Japan between July and September, 2008. Items on the questionnaire included self-reported oral status, use of dentures, use of regular medication, oral problems, cleaning of teeth/dentures and dental care utilization patterns. The results showed that 135 (64.0%) of the responders had visited a dentist in the past year, 185 (87.7%) had visited the same dentist and 85 (40.3%) had had regular dental check-ups. A stepwise multiple logistic regression analysis adjusting for age and sex revealed that the factors associated with regular dental check-ups were significantly higher ADLs (odds ratio (OR)=0.439 in the partially insured and 0.192 in the fully insured in comparison with healthy subjects, p=0.0012), visiting the same dentist (OR=11.978 in comparison with not visiting the same dentist, p=0.0183) and cleaning teeth/dentures three or more times per day (OR=1.962 in comparison with cleaning them two or fewer times per day, p=0.0368). In this study, a higher ADL, visiting the same dentist and cleaning teeth/dentures three or more times per day were associated with having regular dental check-ups in the elderly. The best predictive factor for regular dental check-ups was a high ADL in the elderly. PMID- 20574131 TI - Factors associated with root surface caries in elderly. AB - The purpose of this study was to determine the risk factors for root surface caries in the elderly and to evaluate the factors associated with gingival recession, one of the main risk factors for root surface caries. A total of 153 elderly people (35 men, 118 women) aged between 60 and 94 years (73.5+/-7.5 years) were surveyed. All participants were relatively healthy elderly who did not need special care in their daily lives. The survey was conducted in Chiba prefecture, Japan, and oral examinations and a questionnaire with face-to-face interviews were also carried out. Correlation analysis revealed that number of present teeth (p<0.001), gingival recession (p<0.001), bleeding on probing (p<0.001) and presence or absence of dentures (p<0.05) were significantly correlated with number of root surface caries. Stepwise multiple linear regression analysis for root surface caries revealed that the risk factors for increasing numbers of teeth with root surface caries were number of teeth with gingival recession (p<0.0001), bleeding on probing (p=0.0017) and self-reported dry mouth (p=0.0454). Sex (p<0.05), number of present teeth (p<0.001), bleeding on probing (p<0.01), the presence or absence of systemic disease (p<0.01), dentures (p<0.01), drinking alcohol (p<0.01) and smoking (p<0.01) were significantly correlated with amount of gingival recession by correlation analysis. Moreover, the risk factors for increasing number of teeth with gingival recession were living in an institution (p=0.0244), number of present teeth (p<0.0001) and smoking (p=0.0037), as determined by stepwise multiple linear regression analysis for gingival recession. PMID- 20574132 TI - A case of congenital midline fistula of the upper lip. AB - Congenital fistulas of the lip are commonly found in the lower lip and accompany cleft lip. They are seen as a symptom of Van der Woude syndrome, which is predominantly hereditary. In contrast, congenital fistulas of the upper lip are rare. A number of hypotheses have been proposed to explain the pathogenesis of fistulas of the upper lip, including fusion failure of facial prominences and absence of mesoblasts, suggesting a relationship between this condition and the development of cleft lip. The pathogenesis of this disorder has been attracting attention. We report the case of a 5-year-old girl with congenital fistula of the upper lip. PMID- 20574133 TI - Oral and maxillofacial surgery with computer-assisted navigation system. AB - Intraoperative computer-assisted navigation has gained acceptance in maxillofacial surgery with applications in an increasing number of indications. We adapted a commercially available wireless passive marker system which allows calibration and tracking of virtually every instrument in maxillofacial surgery. Virtual computer-generated anatomical structures are displayed intraoperatively in a semi-immersive head-up display. Continuous observation of the operating field facilitated by computer assistance enables surgical navigation in accordance with the physician's preoperative plans. This case report documents the potential for augmented visualization concepts in surgical resection of tumors in the oral and maxillofacial region. We report a case of T3N2bM0 carcinoma of the maxillary gingival which was surgically resected with the assistance of the Stryker Navigation Cart System. This system was found to be useful in assisting preoperative planning and intraoperative monitoring. PMID- 20574134 TI - Effect of prodromal angina pectoris on the infarct progression in patients with first ST-elevation acute myocardial infarction. AB - BACKGROUND: Prodromal angina pectoris (AP) has a cardioprotective effect by the mechanism of ischemic preconditioning, and the QRS score on the admission electrocardiogram (ECG) reflects myocardial damage at presentation. This study was undertaken to investigate the effect of prodromal AP on infarct progression after the onset of acute myocardial infarction (AMI). METHODS AND RESULTS: The study group comprised 291 patients with a first ST-elevation AMI who underwent coronary angiography within 24 h of symptom onset. QRS score was calculated from the admission ECG. Patients were divided into 3 groups according to elapsed time from onset of AMI to angiography: early group (<2 h), intermediate group (2-6 h) and late group (6-24 h). Prodromal AP was defined as angina occurring 24 h before the onset of AMI. Patients with prodromal AP (n=101; 35%) had a significantly lower QRS score than those without (2.4+/-2.4 vs 3.2+/-3.0, P=0.02). In patients without prodromal AP, the QRS score linearly increased as elapsed time increased: 2.6+/-2.8, 3.0+/-3.0 and 5.5+/-2.9 in the early, intermediate and late groups, respectively. In patients with prodromal AP, the QRS score remained low until 6 h after onset and then increased: 2.0+/-1.8, 2.0+/-2.1, and 4.1+/-3.3, respectively. CONCLUSIONS: The findings suggested that prodromal AP might delay infarct progression during the early hours after the onset of AMI and extend the window of time for reperfusion therapy. PMID- 20574135 TI - Coadministration of carvedilol attenuates nitrate tolerance by preventing cytochrome p450 depletion. AB - BACKGROUND: Long-term administration of nitroglycerin (NTG) causes tolerance secondary to increased vascular formation of reactive oxygen species. Carvedilol, which has potent antioxidant activity in addition to functioning as an adrenergic blocker, prevents nitrate tolerance by a still to be elucidated mechanism. The present study investigated how carvedilol attenuates nitrate tolerance, particularly with reference to cytochrome P450 (CYP), an enzyme involved in the development of tolerance. METHODS AND RESULTS: Male Wistar rats were subjected to 48-h continuous infusion of NTG alone (0.5 mg/h) or NTG with concomitant carvedilol (20 or 100 microg/h), and then compared with vehicle-treated rats (4 groups; n=6 in each group). Following the continuous administration, nitrate tolerance, assessed by bolus NTG injections, was hemodynamically prevented by coadministration of carvedilol. Levels of CYP1A1/1A2, superoxide production, and phosphorylated vasodilator-stimulated phosphoprotein at serine 239 (P-VASP) were examined in the aortic wall and heart tissue. When NTG alone was continuously administered, vascular superoxide was produced, there was a decrease in the cardiac CYP1A1/1A2 level, and depletion of P-VASP. However, each of these changes induced by continuous NTG administration was significantly attenuated by coadministration of carvedilol and the extent of attenuation was more pronounced at the higher dose (100 microg/h). CONCLUSIONS: Coadministration of carvedilol attenuates nitrate tolerance through maintenance of NO/cGMP pathway activity by preventing free radical generation and CYP depletion. PMID- 20574136 TI - Comparative study of bezafibrate and pravastatin in patients with coronary artery disease and high levels of remnant lipoprotein. AB - BACKGROUND: Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. METHODS AND RESULTS: Remnant lipoprotein levels were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (>or=5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. CONCLUSIONS: Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels. PMID- 20574137 TI - Long-term clinical outcome after endovascular treatment in patients with intermittent claudication due to iliofemoral artery disease. AB - BACKGROUND: The natural history of patients with intermittent claudication (IC) has been reported, but little is known about that of claudicant patients after endovascular therapy (EVT). METHODS AND RESULTS: A total of 271 consecutive patients (mean age, 68+/-6 years, 82% men) with IC were treated with EVT for a de novo iliofemoral lesion. Primary patency was defined as treated vessel without re stenosis and repeat revascularization. Major adverse cardiovascular event (MACE) included death, myocardial infarction and stroke. Median follow-up interval was 11.7+/-2.9 years. During the follow-up period, 132 patients died (cardiovascular death; 66%). Major amputation was performed in 4 patients. Primary patency rate was 82%, 79%, and 78% at 5, 10 and 15 years, respectively. Freedom from all-cause death (MACE) was 73% (69%), 58% (49%), and 43% (34%) at 5, 10 and 15 years. On multivariate Cox regression, Trans-Atlantic Inter-society Consensus grade C/D, and involvement of femoropopliteal lesion were independent predictors of primary patency. Independent predictors for overall survival were age, left ventricular dysfunction (ejection fraction <40%), coronary artery disease, diabetes, chronic kidney disease and below-the-knee disease. CONCLUSIONS: Regardless of good clinical patency of treated vessel in patients with IC, survival was poor. Independent predictors were different between long-term patency and late mortality. PMID- 20574138 TI - Maternal nutrition and long-term consequences of the offspring. PMID- 20574139 TI - Clinical features of primary hyperthyroidism caused by Graves' disease admixed with resistance to thyroid hormone (P453T). AB - A 34-year-old Japanese woman was referred to the hospital because of general fatigue and palpitations. She was diagnosed as having resistance to thyroid hormone (RTH) and Hashimoto's thyroiditis at the age of 28. She felt general fatigue, palpitations, heat intolerance, and sweating for 6 months. Thyroid function tests demonstrated elevated levels of free triidothyronine (T3) and free thyroxine (T4) that were above detectable ranges and a completely suppressed level of TSH that was below the detectable range. Titers of anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) were positive. A 20 minute Technetium-m99 pertechnetate thyroid uptake imaging study showed an elevated value of 39.53% and a normal-shaped thyroid gland. These results indicated that Graves' disease (GD) caused primary hyperthyroidism. Pituitary and peripheral tissues responded to the presence of excess thyroid hormone in the patient. Oral administration of methimazole was started and continued for 1 year 10 months, after which it was ceased. Two years after the cessation of methimazole treatment, level of free T4 was elevated compared to reference range, but levels of TSH and free T3 were within normal reference ranges. Titers of TRAb and TSAb remained negative for 2 years. These findings indicated that the patient's GD was in remission. In conclusion, it is difficult to make a differential diagnosis between GD with RTH and GD alone if RTH is not diagnosed before the onset of GD. An antithyroid drug is able to cause the remission of GD with RTH. PMID- 20574141 TI - [What the patients want in allergy treatment]. PMID- 20574140 TI - Seroprevalence of Bartonella vinsonii subsp. berkhoffii in urban and rural dogs in Turkey. AB - The seroprevalence of Bartonella vinsonii subsp. berkhoffii was investigated in stray urban dogs and shepherd and farm guard dogs from rural areas sampled from 10 provinces of Turkey. Sera from 855 dogs were examined for the presence of anti B. vinsonii subsp. berkhoffii antibodies by indirect fluorescent antibody test. Overall, 56 (6.6%) of the 855 dogs examined, including 16 (3%) of the 522 stray dogs and 40 (12%) of the 333 rural dogs, were seropositive. This is the first report on prevalence of antibodies to B. vinsonii subsp. berkhoffii in dogs in Turkey. PMID- 20574142 TI - [Lung tissue stem cells]. PMID- 20574143 TI - [Laryngeal allergy]. PMID- 20574144 TI - [Clinical survey to understand real asthma life for patients-I]. AB - BACKGROUND: Although several studies investigate the level of asthma control, real asthma life for patients, factors that influence on patients satisfaction, and reasons for irregular visit have not been studied in Japan. METHODS: One thousand and two hundreds patients with adult asthma were studied by internet based questionnaire from March 25th to 31st in 2009. Satisfaction for asthma management was scored from 0 to 10 and then divided into three groups, such as high (10-8), middle (7-4), and low (3-0) groups. Major questions for these patients were precise explanations on diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Furthermore, factors that might have influences on non-adherence and irregular visit by patients were investigated. RESULTS: Severity of the patients enrolled into this study was 34.8% in mild asthma, 19.2% in moderate asthma, and 7.8% in severe asthma. 81.6% of patients were treated with inhaled corticosteroids or combination of inhaled corticosteroid and long acting inhaled beta(2)-agonist. The average score for satisfaction of patients was 6.83 and satisfaction of patients was 43.2% in high, 48.9% in middle, and 7.9% in low group. Patients with low satisfaction group had not been precisely explained the diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Less non-adherence and low number of irregular visits were observed in patients with high satisfaction group. CONCLUSION: Although this study was performed by internet-based questionnaire and might not reflect the real management of asthma in Japan, the lower the satisfaction, the less patients received explanations on the diagnosis of asthma, goal of the treatment, and treatment with medications by the doctors. Therefore, explanations for these factors may have great influences on non-adherence and irregular visits in patients with asthma. PMID- 20574145 TI - [Questionnaire for determining relationship between nasal and asthma symptoms]. AB - BACKGROUND: The interaction between allergic rhinitis and bronchial asthma is well known. However, there is little epidemiological data on the relationship between nasal diseases and asthma, especially in Japan. METHODS: We administered a questionnaire to 126 patients to examine the frequency of associations between nasal and asthma symptoms in patients with both nasal disease and asthma. We also investigated in which type of patients the asthma symptoms were affected by changes in nasal symptoms. RESULTS: Thirty-eight patients (30%) were aware that their asthma was worsened by exacerbated nasal disease, and nasal treatment improved asthma in 28 patients (22%). The influence of changes in nasal symptoms on asthma symptoms was stronger in patients lacking good asthma control. The relationship between nasal and asthma symptoms tended to be stronger in patients with sinusitis. CONCLUSION: About 30% of patients with nasal disease and asthma reported an association between their nasal and asthma symptoms. Nasal treatment is considered to be important for asthma control, especially in patients with asthma symptoms. These results suggested the important role of comprehensive allergy care in controlling both nasal disease and asthma. PMID- 20574146 TI - [Risk factors for persistent and relapsed childhood-onset asthma]. AB - BACKGROUND: The aim of this study was to identify factors responsible for childhood-onset persistent asthma and childhood-onset asthma relapsing in adulthood. METHODS: We compared a number of potential risk factors for asthma among 608 patients with childhood-onset persistent asthma (onset at 15 years of age or younger) and 286 patients with childhood-onset asthma (onset at 20 years or younger) that had relapsed after a period of remission longer than 2 years. RESULTS: Multiple linear regression analysis revealed that the factors associated with childhood-onset persistent asthma were a past or present history of allergic rhinitis (p=0.001) and high serum total IgE concentration (> or =300 IU/ml; p=0.007). The factors associated with relapse of childhood-onset asthma were female sex (p=0.001), younger onset age (p=0.036), and smoking (current or former; p<0.001). CONCLUSION: Our findings indicate that a past or present history of allergic rhinitis and high serum IgE level are significant risk factors for childhood-onset persistent asthma, and that female sex and a history of smoking are risk factors for relapse of childhood-onset asthma. Fortunately, exposure to tobacco smoke is a controllable risk factor. PMID- 20574147 TI - [Actigraphy for the assessment of sleep quality in pediatric atopic dermatitis patients]. AB - BACKGROUND: Good sleep is essential for the growth and the development of children. However, sleep is often impaired in patients with atopic dermatitis (AD). It is important to assess the sleep quality in pediatric AD patients. For that purpose, we utilized actigraphy as an objective method for the assessment of sleep quality. METHODS: Childhood patients with AD (16 cases) and 8 non-allergic volunteers were recruited. Actiwatch (AW-64) was attached to each subject's wrist for 11 days at maximum. Sleep parameters were calculated with Actiware and compared among various patient groups. RESULTS: Results demonstrate that sleep was significantly compromised in patients with AD, according to the severity. Subjective scoring of the sleep quality by parents showed limited correlation with actigraphy. CONCLUSION: Actigraphy is an objective and unobtrusive method to measure the sleep quality in childhood AD patients and can provide useful outcome in clinical trial. PMID- 20574148 TI - JimMY on the stage: Linking DNA damage with cell adhesion and motility. AB - Cellular DNA undergoes constant assault from a wide range of genotoxic stress. In order to maintain genome integrity, cells develop a repertoire of sophisticated systems to detect DNA damage and mediate cellular responses to DNA damage. Defects in the DNA damage response have been implicated in a variety of disorders including aging and cancer. Tumor suppressor p53 is a key intermediate in DNA damage response by inducing cell cycle arrest to allow repair or promoting apoptosis to eliminate irreparably damaged cells. A recent study described a novel layer of p53-mediated cellular response to DNA damage, i.e., modulation of cell adhesion and motility. JMY, a p53 co-factor, was demonstrated to be a multifunctional protein that coordinates cell adhesion and motility with nuclear p53 response. These results suggest that abnormal JMY activity and/or localization could contribute to tumor invasion and reveal JMY as a potential therapeutic target. PMID- 20574149 TI - Neuronal cell adhesion genes: Key players in risk for schizophrenia, bipolar disorder and other neurodevelopmental brain disorders? AB - The major mental disorders, schizophrenia and bipolar disorder are substantially heritable. Recent genomic studies have identified a small number of common and rare risk genes contributing to both disorders and support epidemiological evidence that genetic susceptibility overlaps between them. Prompted by the question of whether risk genes cluster in specific molecular pathways or implicate discrete mechanisms we and others have developed hypothesis-free methods of investigating genome-wide association datasets at a pathway-level. The application of our method to the 212 experimentally-derived pathways in the Kyoto Encycolpaedia of Genes and Genomes (KEGG) database identified significant association between the cell adhesion molecule (CAM) pathway and both schizophrenia and bipolar disorder susceptibility across three GWAS datasets. Interestingly, a similar approach applied to an autistic spectrum disorders (ASDs) sample identified a similar pathway and involved many of the same genes. Disruption of a number of these genes (including NRXN1, CNTNAP2 and CASK) are known to cause diverse neurodevelopmental brain disorder phenotypes including schizophenia, autism, learning disability and specific language disorder. Taken together these studies bring the CAM pathway sharply into focus for more comprehensive DNA sequencing to identify the critical genes, and investigate their relationships and interaction with environmental risk factors in the expression of many seemingly different neurodevelopmental disorders. PMID- 20574150 TI - The antitumor efficacy of IL-24 mediated by E1A and E1B triple regulated oncolytic adenovirus. AB - BACKGROUND: IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus, Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24. in which E1A was engineered to target Rb (retinoblastoma) deficient or dysfunctional tumors. The survivin promoter (sp), was used to drive expression of IL-24, thereby allowing it to target most tumors. Finally, the 55 KDa gene of E1B was also deleted, thereby preventing replication in normal cells. RESULTS: Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 showed enhanced antitumor effects over the E1, singly regulated oncolytic adenovirus, ONYX-015, in in vitro experiments. Furthermore, Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 could effectively inhibit the progression of NCI-H460 lung carcinoma xenografts in nude mice. METHODS: The antitumor effect of Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 was assessed by MTT assay and crystal violet staining in a panel of tumor cells. Cell staining and western blotting for caspase activation were used to assess apoptosis. We assessed the antitumor effects of Ad.sp.E1A((Delta24)).E1B((Delta55)).IL-24 in a xenograft model. CONCLUSION: This is the first study to use an E1A and E1B triple regulated oncolytic adenovirus vector carrying IL-24 to treat large tumors. We attained efficient antitumor effects both in vitro and in vivo, which provides an experimental foundation for clinical cancer therapy. PMID- 20574151 TI - miRNA-520b and miR-520e sensitize breast cancer cells to complement attack via directly targeting 3'UTR of CD46. AB - MicroRNAs (miRNAs), non-coding RNAs that function as post-transcriptional gene regulators, play a pivotal role in cancer development. In the present study, we elucidated the roles of miR-520b and miR-520e in breast cancer cells. We examined the expression levels of miR-520b and miR-520e in the immortalized breast cell line, HBL-100, and in three breast cancer cell lines: MCF-7, LM-MCF-7 and MDA-MB 231. We show the expression levels of miR-520b and miR-520e in the breast cancer cell lines were lower than that in the HBL-100 cells. Furthermore, the breast cancer cell lines showed less sensitivity to complement-dependent cytotoxicity (CDC). We found that overexpression of miR-520b and miR-520e increases the sensitivity of the breast cancer cells to CDC, whereas further suppression of miR 520b and miR-520e decreases the sensitivity of the breast cancer cells to CDC. We then demonstrate that miR-520b and miR-520e are able to directly target the 3'untranslated regions (3'UTR) of the membrane-bound complement regulatory protein CD46; suggesting that miR-520b and miR-520e down-regulate CD46 at post transcriptional level. Enzyme-linked immunosorbent assay (ELISA) showed that overexpression of miR-520b and miR-520e results in the increased expression of C3b, which is mediated by downregulated CD46. These results suggest that miRNA 520b and miR-520e mediated down-regulation of CD46 induces opsonization of cancer cells via an alternative pathway resulting in complement activation. Thus, we conclude that miR-520b and miR-520e contribute to CDC in breast cancer cells via directly targeting the 3'UTR of CD46. PMID- 20574152 TI - Molecular therapy for melanoma: useful and not useful targets. PMID- 20574153 TI - The use of 5-alpha reductase inhibitors for the prevention of prostate cancer. AB - The use of 5-alpha-reductase inhibitors has been studied not only in benign prostatic hyperplasia, but as a chemopreventive strategy in prostate cancer. Both finasteride and dutasteride, 5 alpha-reductase inhibitors (5ARI), have been shown to decrease the risk of prostate cancer. The results of the REDUCE trial using the dual alpha-reductase isoenzyme inhibitor dutasteride, has recently been published by Andriole et al. in the New England Journal of Medicine. Certain considerations regarding its use and applicability to men with high risk of developing prostate cancer are herein discussed. PMID- 20574154 TI - Overexpressed Id-1 is associated with patient prognosis and HBx expression in hepatitis B virus-related hepatocellular carcinoma. AB - Id-1 is a member of the helix-loop-helix protein family and is involved in multiple biological processes, including development, proliferation, angiogenesis and carcinogenesis. However, the role of Id-1 in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still unclear. In this study, Id-1 expression in 96 tumor specimens of HBV-related HCC was detected by immunohistochemical (IHC) staining. The relationship between the Id-1 expression grade and patient clinicopathological features was studied. In addition, the relationship between Id-1 expression and disease-free and overall survival times was analyzed. Colocalization of Id-1 and HBx was investigated by confocal laser scanning microscopy. The effect of HBx on Id-1 expression was studied in vitro using the HepG2 HCC cell line. Overexpression of Id-1 was found in 64.6% (62/96) of tumor specimens and was correlated with the histological grade, portal vein invasion, lymph node metastasis, HBsAg and Child-Pugh classification. Patients with Id-1 overexpression had both shorter disease-free and overall survival times. Besides, colocalization of Id-1 and HBx was found by paired IHC and confocal study. The expression of Id-1 was positively correlated to that of HBx. In vitro ectopic expression of HBx in HepG2 cells significantly increased Id-1 mRNA and protein expression. To our knowledge, this is the first report suggesting that Id-1 expression is at least partially regulated by HBx and may serve as a potential prognostic marker for HBV-related HCC. PMID- 20574155 TI - VMY-1-103, a dansylated analog of purvalanol B, induces caspase-3-dependent apoptosis in LNCaP prostate cancer cells. AB - The 2,6,9-trisubstituted purine group of cyclin dependent kinase inhibitors have the potential to be clinically relevant inhibitors of cancer cell proliferation. We have recently designed and synthesized a novel dansylated analog of purvalanol B, termed VMY-1-103, that inhibited cell cycle progression in breast cancer cell lines more effectively than did purvalanol B and allowed for uptake analyses by fluorescence microscopy. ErbB-2 plays an important role in the regulation of signal transduction cascades in a number of epithelial tumors, including prostate cancer (PCa). Our previous studies demonstrated that transgenic expression of activated ErbB-2 in the mouse prostate initiated PCa and either the overexpression of ErbB-2 or the addition of the ErbB-2/ErbB-3 ligand, heregulin (HRG), induced cell cycle progression in the androgen-responsive prostate cancer cell line, LNCaP. In the present study, we tested the efficacy of VMY-1-103 in inhibiting HRG-induced cell proliferation in LNCaP prostate cancer cells. At concentrations as low as 1 MUM, VMY-1-103 increased both the proportion of cells in G(1) and p21(CIP1) protein levels. At higher concentrations (5 MUM or 10 MUM), VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity and induction of p53 phosphorylation, caspase-3 activity and PARP cleavage. Treatment with 10 MUM Purvalanol B failed to either influence proliferation or induce apoptosis. Our results demonstrate that VMY-1-103 was more effective in inducing apoptosis in PCa cells than its parent compound, purvalanol B, and support the testing of VMY-1-103 as a potential small molecule inhibitor of prostate cancer in vivo. PMID- 20574156 TI - Stromal CD10 and SPARC expression in ductal carcinoma in situ (DCIS) patients predicts disease recurrence. AB - The current classification of ductal carcinoma in situ (DCIS) is based on nuclear grade, architectural differentiation and the presence of necrosis that does not adequately predict the likelihood of recurrence after breast conserving therapy; therefore, there is a critical need to identify novel predictors of DCIS progression. Ninety seven cases of DCIS were included in the study. CD10 and SPARC expression in tumor stroma was assessed by standard immunoperoxidase method with ani-CD 10 and anti-SPARC antibodies. The staining was scored semi quantitatively as negative, weak or strong. Statistical analysis was performed using the Fisher's exact test. Multivariable analysis was conducted utilizing Exact Logistic Regression software (SAS 9.1 and LogExact). A significant association was observed between the recurrence status and time to recurrence with expression of CD10 (p < 0.001) and SPARC (p < 0.001). When combining both SPARC and CD10 expression there was a strong correlation with the shortest time to recurrence. Stromal CD10 and SPARC expression are new markers of an increased risk for DCIS recurrence, independent of commonly assessed clinical parameters. Thus, stromal CD10 and SPARC expression levels are promising markers of DCIS recurrence and warrant evaluation in larger prospective studies. PMID- 20574157 TI - Finding a fitting shoe for Cinderella: searching for an autophagy inhibitor. AB - Vps34 is the ancestral phosphatidylinositol 3-kinase (PtdIns3K) isoform and is essential for endosomal trafficking of proteins to the vacuole/lysosome, autophagy and phagocytosis. Vps34-containing complexes associate with specific cellular compartments to produce PtdIns(3)P. Understanding the roles of Vps34 has been hampered by the lack of potent, specific inhibitors. To boost development of Vps34 inhibitors, we determined the crystal structures of Vps34 alone and in complexes with multitargeted PtdIns3K inhibitors. These structures provided a first glimpse into the uniquely constricted ATP-binding site of Vps34 and enabled us to model Vps34 regulation. We showed that the substrate-binding "activation" loop and the flexibly attached amphipathic C-terminal helix are crucial for catalysis on membranes. The C-terminal helix also suppresses ATP hydrolysis in the absence of membranes. We propose that membrane binding shifts the C-terminal helix to orient the enzyme for catalysis, and the Vps15 regulatory subunit, which binds to this and the preceding helix, may facilitate this process. This C terminal region may also represent a target for specific, non-ATP-competitive PtdIns3K inhibitors. PMID- 20574158 TI - Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia. AB - The present study evaluated autophagy activation in astrocytes and its contribution to astrocyte injury induced by cerebral ischemia and hypoxia. Focal cerebral ischemia was induced by permanent middle cerebral artery occlusion (pMCAO) in rats. In vitro hypoxia in cultured primary astrocytes was induced by the oxygen-glucose deprivation (OGD). Alterations of astrocytes were evaluated with astroglia markers glial fibrillary acidic protein (GFAP). The formation of autophagosomes in astrocytes was examined with transmission electron microscopy (TEM). The expression of autophagy-related proteins were examined with immunoblotting. The role of autophagy in OGD or focal cerebral ischemia-induced death of astrocytes was assessed by pharmacological inhibition of autophagy with 3-methyladenine (3-MA) or bafilomycin A(1) (Baf). The results showed that GFAP staining was reduced in the infarct brain areas 3-12 h following pMCAO. Cerebral ischemia or OGD induced activation of autophagy in astrocytes as evidenced by the increased formation of autophagosomes and autolysosomes and monodansylcadaverine (MDC)-labeled vesicles; the increased production of microtubule-associated protein 1 light chain 3 (LC3-II ); the upregulation of Beclin 1, lysosome associated membrane protein 2 (LAMP2) and lysosomal cathepsin B expression; and the decreased levels of cytoprotective Bcl-2 protein in primary astrocytes. 3-MA inhibited OGD-induced the increase in LC3-II and the decline in Bcl-2. Furthermore, 3-MA and Baf slightly but significantly attenuated OGD-induced death of astrocytes. 3-MA also significantly increased the number of GFAP-positive cells and the protein levels of GFAP in the ischemic cortex core 12 h following pMCAO. These results suggest that ischemia or hypoxia-induced autophagic/lysosomal pathway activation may at least partly contribute to ischemic injury of astrocytes. PMID- 20574159 TI - Proteolytic pathways involved in modulation of CD20 levels. AB - Recent observations indicate that rituximab-resistant lymphoma cells exhibit upregulation of components of the ubiquitin-proteasome system (UPS). Therefore, proteasome inhibitors including the clinically approved bortezomib might influence the levels of CD20, a rituximab target antigen. We observed that incubation of tumor cells with rituximab leads to increased levels of ubiquitinated CD20. However, inhibition of the UPS is not associated with upregulation, but rather with a counterintuitive downregulation of surface CD20 levels that increases resistance of tumor cells to rituximab-mediated cytotoxicity. Although preliminary observations indicate that CD20 might be a substrate for two proteolytic systems, the mechanisms as well as significance of these findings require further studies. PMID- 20574160 TI - The Arabidopsis thaliana ACBP3 regulates leaf senescence by modulating phospholipid metabolism and ATG8 stability. AB - Bulk degradation and nutrient recycling are events associated with autophagy. The core components of the autophagy machinery have been elucidated recently using molecular and genetic approaches. In particular, two ubiquitin-like proteins, ATG8 and ATG12, which conjugate with phosphatidylethanolamine (PE) and ATG5, respectively, forming ATG8-PE and ATG12-ATG5 complexes, were shown to be essential in autophagosome formation. Our recent findings reveal that the Arabidopsis thaliana acyl-CoA-binding protein ACBP3 binds the phospholipid PE in vitro and that ACBP3 overexpression and downregulation correlate with PE composition in rosettes. Furthermore, ACBP3-overexpressors (ACBP3-OEs) display accelerated salicylic acid-dependent leaf senescence resembling the phenotype of Arabidopsis knockout (KO) mutants defective in autophagy-related (ATG) proteins. Consistently, downregulation of ACBP3 (ACBP3-KOs) delays dark-induced leaf senescence. By analysis of transgenic Arabidopsis expressing GFP-ATG8e as well as those co-expressing ACBP3-OE and GFP-ATG8e, we showed that ACBP3-overexpression disrupts autophagosome formation and enhanced degradation of ATG8 under starvation conditions, suggesting that ACBP3 is an important regulator of the ATG8-PE complex via its interaction with PE. Here, a working model for the role of ACBP3 in the regulation of autophagy-mediated leaf senescence is presented. PMID- 20574161 TI - The road not taken: a systems level strategy for analyzing the cell death network. AB - Three main cell death phenotypes have been identified in mammalian systems: apoptosis, autophagy and programmed necrosis. Currently, the field lacks systems level approaches to assess how the intricate crosstalk and interconnectivity between the different death functional modules affect the cell's final outcome. In order to dissect the cell death network's architecture, we developed a platform that measures the outcome of single and double RNAi-mediated perturbations of different apoptotic and autophagic genes on both the final cell death performance, and the pattern of protein connectivity. We applied this platform on cells exposed to a DNA damaging drug, and identified several levels of connectivity between apoptosis and autophagy. In addition, using computational methods we suggested a novel biochemical pathway providing a connection between ATG5 and caspase-3. Scaling up this platform into hundreds of perturbations will reveal novel principles of the organization of the cell death network, and will provide the basis for future computational modeling. PMID- 20574163 TI - Programming differentiation potential in mesenchymal stem cells. AB - Cell fate decisions are largely programmed by interactions between multiple layers of regulation of gene expression. Among these, epigenetic states have been extensively examined, mostly in the context of embryonic stem cell differentiation. Recent studies however have focused on understanding chromatin based mechanisms of differentiation of adult progenitor cells into specific lineages but not others. The results point to the view that promoter DNA methylation patterns are not the primary determinant of gene activation potential and differentiation capacity of mesenchymal stem cells. Post-translational histone modifications on promoters contribute to establishing a permissive state of differentiation, but cannot either, based on current knowledge, predict transcriptional activation outcome. Additional regulatory layers need to be examined to be able to explain cell fate commitment and ultimately predict cell fate. PMID- 20574164 TI - Low dynamin 2 expression is associated with tumor invasion and metastasis in invasive squamous cell carcinoma of cervix. AB - Dynamin 2 is known as a protein involved in cell migration and endocytosis. We aimed to investigate the association between dynamin 2 expressions and tumor progression in early cervical carcinoma (IB1-IIA). Dynamin 2 expression was evaluated at protein level in thirty seven paraffin-embedded, formalin-fixed tissues including four normal cervix tissues and compared with pathologic risk factors for recurrence after surgery in thirty three patients with squamous cell carcinoma of the cervix. The expression of dynamin 2 was not different according to clinical stage and lympho-vascular space invasion. However, there were inverse correlations between dynamin 2 expression and the depth of invasion in cervix (p = 0.003) and lymph node (LN) metastasis (p = 0.001). To evaluate the mechanism of dynamin 2 in tumor invasion and metastasis, we performed an in vitro experiment with dynamin 2 siRNA using several cervical carcinoma cell lines such as HeLa, MS751 and SiHa cells. We found the inhibition of dynamin 2 using specific siRNA enhanced the expression of matrix metalloproteinase-2. These results suggested that dynamin 2 might be involved in preventing tumor invasion and LN metastasis, possibly in relation with extracellular matrix degradation, and may be a prognostic marker for these risk factors in early squamous cell carcinoma of the cervix. PMID- 20574162 TI - Mechanistic and biological aspects of helicase action on damaged DNA. AB - Helicases catalytically unwind structured nucleic acids in a nucleoside triphosphate-dependent and directionally specific manner, and are essential for virtually all aspects of nucleic acid metabolism. ATPase-driven helicases which translocate along nucleic acids play a role in damage recognition or unwinding of a DNA tract containing the lesion. Although classical biochemical experiments provided evidence that bulky covalent adducts inhibit DNA unwinding catalyzed by certain DNA helicases in a strand-specific manner (i.e., block to DNA unwinding restricted to adduct residence in the strand the helicase translocates), recent studies suggest more complex arrangements that may depend on the helicase under study, its assembly in a protein complex, and the type of structural DNA perturbation. Moreover, base and sugar phosphate backbone modifications exert effects on DNA helicases that suggest specialized tracking mechanisms. As a component of the replication stress response, the single-stranded DNA binding protein Replication Protein A (RPA) may serve to enable eukaryotic DNA helicases to overcome certain base lesions. Helicases play important roles in DNA damage signaling which also involve their partnership with RPA. In this review, we will discuss our current understanding of mechanistic and biological aspects of helicase action on damaged DNA. PMID- 20574165 TI - Frequent hyperphosphorylation of AS160 in breast cancer. AB - Enhanced cellular glucose uptake is a frequent characteristic of malignant cells. The Akt substrate of 160 kDa (AS160) is a newly discovered substrate for the protein kinase AKT and phosphorylation of AS160 (p-AS160) was recently recognized to play an important role in glucose transport. However, studies on AS160 in cancer do not yet exist. The aim of the present study was to investigate the p AS160 level and its correlation with clinicopathological parameters and various biological markers in breast cancer. Results showed that in breast cancer, phosphorylation of AS160 at the key residue T642 was significantly (p < 0.001) higher than that in normal adjacent tissues. P-AS160 staining was positive in 75 of 81 cases (92.6%), including 32 with weak-(score 1), 31 with moderate-(score 2) and 12 with strong immunoreactivity (score 3). P-AS160 was inversely correlated with patient age (p = 0.041) and positively correlated with tumor size (p = 0.013) and the cell proliferation marker Ki-67 (MIB-1) (p < 0.001). This is the first study of AS160 in cancer. Our results show that AS160 phosphorylation level is frequently increased in breast cancer. These results implicate a possible role of AS160 in human breast tumorigenesis and suggest that p-AS160 might be useful as a marker and a potential novel treatment target for breast cancer. PMID- 20574166 TI - BZL101, a phytochemical extract from the Scutellaria barbata plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype. AB - BZL101 is an aqueous extract from the Scutellaria barbata plant shown to have anticancer properties in a variety of human cancers. In order to determine its efficacy on human reproductive cancers, we assessed the responses of two human breast cancer cell lines, estrogen sensitive MCF7 and estrogen insensitive MDA-MB 231, and of two human prostate cancer cell lines, androgen sensitive LNCaP and androgen insensitive PC3 which are human cell lines that represent early and late stage reproductive cancers. BZL101 inhibited reproductive cancer growth in all cell lines by regulating expression levels of key cell cycle components that differ with respect to the cancer cell phenotypes. In early stage estrogen sensitive MCF7 cells, BZL101 induced a G1 cell cycle arrest and ablated expression of key G1 cell cycle regulators Cyclin D1, CDK2 and CDK4, as well as growth factor stimulatory pathways and estrogen receptor-alpha expression. Transfection of luciferase reporter plasmids revealed that the loss of CDK2, CDK4 and estrogen receptor-alpha transcript expression resulted from the BZL-dependent ablation of promoter activities. BZL101 growth arrests early stage androgen sensitive LNCaP cells in the G2/M phase with corresponding decreases in Cyclin B1, CDK1 and androgen receptor expression. In late stage hormone insensitive breast (MDA-MB-231) and prostate (PC3) cancer cells, BZL101 induced an S phase arrest with corresponding ablations in Cyclin A2 and CDK2 expression. Our results demonstrate that BZL101 exerts phenotype specific anti-proliferative gene expression responses in human breast and prostate cancer cells, which will be valuable in the potential development of BZL-based therapeutic strategies for human reproductive cancers. PMID- 20574167 TI - The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes. AB - Adipose tissue lipoatrophy caused by caveolin gene deletion in mice is not linked to defective adipocyte differentiation. We show that adipose tissue development cannot be rescued by endothelial specific caveolin-1 re-expression, indicating primordial role of caveolin in mature adipocytes. Partial or total caveolin deficiency in adipocytes induced broad protein expression defects, including but not limited to previously described downregulation of insulin receptor. Global alterations in protein turnover, and accelerated degradation of long-lived proteins were found in caveolin-deficient adipocytes. Lipidation of endogenous LC3 autophagy marker and distribution of GFP-LC3 into aggregates demonstrated activated autophagy in the absence of caveolin-1 in adipocytes. Furthermore, electron microscopy revealed autophagic vacuoles in caveolin-1 deficient but not control adipocytes. Surprisingly, significant levels of lipidated LC3-II were found around lipid droplets of normal adipocytes, maintained in nutrient-rich conditions or isolated from fed mice, which do not display autophagy. Altogether, these data indicate that caveolin deficiency induce autophagy in adipocytes, a feature that is not a physiological response to fasting in normal fat cells. This likely resulted from defective insulin and lipolytic responses that converge in chronic nutrient shortage in adipocytes lacking caveolin-1. This is the first report of a pathological situation with autophagy as an adaptative response to adipocyte failure. PMID- 20574168 TI - A reporter cell system to monitor autophagy based on p62/SQSTM1. AB - Macroautophagy (hereafter referred to as autophagy) is a catabolic pathway to isolate and transport cytosolic components to the lysosome for degradation. Recently, autophagy receptors, like p62/SQSTM1 and NBR1, which physically link autophagic cargo to ATG8/MAP1-LC3/GABARAP family members located on the forming autophagic membranes, have been identified. To identify conditions or compounds that affect autophagy, cell systems that efficiently report on autophagic flux are required. Here we describe reporter cell systems based on induced expression of GFPp62, GFP-NBR1 or GFP-LC3B. The degradation of the fusion proteins was followed after promoter shut-off by flow cytometry of live cells. All three fusion proteins were degraded at a basal rate by autophagy. Surprisingly, the basal degradation rate varied for the three reporter fusion proteins. GFP-LC3B was the most stable protein. GFP-NBR1 was most efficiently degraded under basal conditions while degradation of GFP-p62 displayed the strongest response to amino acid starvation. GFP-p62 was found to perform the best of the tested reporters. Single cell analysis of autophagic flux by flow cytometry allows estimates of heterogeneous cell populations. The feasibility of this approach was demonstrated using transient overexpression of a dominant negative ULK1 kinase and siRNA mediated knockdown of LC3B to inhibit autophagic degradation of GFP-p62. The inducible GFP-p62 cell system allows quantification by several approaches and will be useful in screening for compounds or conditions that affect the rate of autophagy. Inducers of autophagy can be identified using rich medium whereas inhibitors are identified under starvation conditions. PMID- 20574169 TI - The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important? AB - Surgical nephrectomy is a procedure that has been performed for nearly 100 years. In the presence of a normal contralateral kidney, such as in a renal transplant donor or child with Wilms tumor, it is a benign procedure without deleterious consequences on the remaining kidney. However, many adults and some children postnephrectomy will develop chronic kidney disease. The non-neoplastic kidney in tumor resections may harbor a large number of developmental and acquired diseases predictive of this outcome or that convey other medically significant information. Examination of the non-neoplastic kidney is a fertile opportunity to identify these unsuspected conditions that may ultimately dictate the subsequent clinical course and influence the medical care provided. This review discusses the consequences of unilateral and partial nephrectomy, and illustrates many conditions that may be encountered in the non-neoplastic cortex with a discussion of their clinical implications. PMID- 20574170 TI - Ocular adnexal lymphomas: a review. AB - Ocular adnexal lymphomas comprise 1% to 2% of all non-Hodgkin lymphomas and about 8% of extranodal lymphomas. They are a heterogeneous group of malignancies, the majority of which are primary extranodal lymphoma with most (up to 80%) of the marginal zone of mucosa associated lymphoid tissue type (MALT lymphoma). This review will encompass the incidence, histology, immunophenotyping, recent advances in molecular and cytogenetics, clinical features including outcome, and prognostic factors. The association with Chlamydia psittaci and the very recently recognized occurrence in the context of IgG4-related sclerosing disease will be discussed. Finally, traditional (surgery, radiotherapy, chemotherapy) and newer forms of therapy (immunotherapy and radioimmunotherapy) will be reviewed. PMID- 20574171 TI - Adenocarcinoma of the upper aerodigestive tract. AB - Although squamous cell carcinoma is the most frequent malignant diagnosis made with upper aerodigestive tract specimens, a myriad of neoplasms can occur throughout the area. Very uncommonly, one encounters adenocarcinomas that cannot be better classified as salivary gland-type neoplasia. This manuscript reviews these tumors, including sinonasal intestinal-type adenocarcinomas, sinonasal low grade and high-grade nonintestinal adenocarcinomas and nasopharyngeal papillary adenocarcinomas. Clinical, histologic, and immunohistochemical features and differential diagnoses are discussed. PMID- 20574172 TI - Smoking-related Small airway disease--a review and update. AB - The term "small airway disease" has been used in reference to abnormalities occurring secondary to cigarette smoking in the context of chronic obstructive pulmonary disease (COPD), and the small airways are the major site of obstruction in patients with COPD. The histologic features associated with smoking-related small airway disease are largely nonspecific and overlap with those of other bronchiolitides. The pathogenesis of smoking-related small airway disease is poorly understood; however, insights into the development of airway remodeling and matrix production continue to evolve. The aim of this article will be to review the histologic findings and pathogenesis of smoking-related small airway disease in the context of COPD, and review other small airway disorders affecting cigarette smokers, namely respiratory bronchiolitis and Langerhans cell histiocytosis, and a newly described entity of respiratory bronchiolitis with fibrosis and associated issues with this entity. PMID- 20574173 TI - Artifacts and organism mimickers in pathology: case examples and review of literature. AB - Despite the impressive advances in pathology and microbiology of recent years, the morphologic recognition of an organism remains a major component in rendering a specific diagnosis of an infectious process, or at minimum, a trigger in the process of identifying an infectious agent. Artifacts and mimickers may pose difficulty to the unwary, and may cause a potential "wild goose chase" that can result in wasted valuable time and resources. Fibrin, collagen exogenous fibers, and bacteria may mimic fungal hyphae. Morphologically altered or treated bacteria and Russel bodies may be mistaken for fungal yeasts, etc. Examples of artifacts and mimickers that may simulate infectious organisms are presented in this article. In addition, a review of literature on the subject, demonstrating a surprising dearth of published articles, despite the frequent encounters of this issue in the daily practice. PMID- 20574174 TI - Mixed Medullary-follicular-derived carcinomas of the thyroid gland. AB - Tumors of the thyroid are subclassified based on the cell of origin and commonly include follicular-derived tumors and C-cell-derived tumors. The most common follicular-derived tumors are papillary carcinoma and follicular carcinoma, whereas the malignant C-cell-derived tumor is medullary thyroid carcinoma. Rare cases in the literature describe patients who have follicular-derived and C-cell derived tumors in the same thyroid gland. These can be synchronous but anatomically separate carcinomas, or they can show some mixing of the 2 components. The mixture may be at an interface, as in collision tumors, or can be throughout the entire lesion, as in true mixed medullary-follicular-derived carcinomas. The clinical, histologic, and molecular features of these mixed tumors and the classification guidelines are reviewed. PMID- 20574176 TI - Osteoclast-rich undifferentiated carcinoma of the urinary bladder: is it really an entity? PMID- 20574177 TI - Urothelial carcinoma in situ of the urinary bladder with columnar cell pattern. PMID- 20574179 TI - Creating healthier lives for our patients and ourselves. PMID- 20574180 TI - Palliative care isn't just for the dying. AB - A nurse wishes her son and family had received it after his cancer diagnosis. PMID- 20574185 TI - The jury's in--staffing laws work. Interview by Carol Potera. PMID- 20574186 TI - Alarm fatigue linked to patient's death. Interview by Laura Wallis. PMID- 20574192 TI - The war on tuberculosis. Interview by Sibyl Shalo. PMID- 20574195 TI - Health care reform: what's in it for nursing? PMID- 20574199 TI - Interventions to promote physical activity in chronically ill adults. AB - OVERVIEW: The importance of promoting physical activity in adults with chronic illness cannot be overstated. Although numerous studies have evaluated interventions developed to increase physical activity in this population, it can be difficult to interpret the results without the benefit of a statistical analysis across studies. A 2008 meta-analysis synthesized the findings of 163 reports on such studies. This article discusses the implications of those findings, describing the strategies and practices commonly used to promote physical activity in chronic illness and identifying those that are most effective. PMID- 20574200 TI - Looking AHEAD for health. Interview by Patrice O'Shaughnessy. PMID- 20574202 TI - Cultivating quality: an evidence-based protocol for managing hypoglycemia. PMID- 20574204 TI - Evidence-based practice step by step: Critical appraisal of the evidence: part I. AB - This is the fifth article in a series from the Arizona State University College of Nursing and Health Innovation's Center for the Advancement of Evidence-Based Practice. Evidence-based practice (EBP) is a problem-solving approach to the delivery of health care that integrates the best evidence from studies and patient care data with clinician expertise and patient preferences and values. When delivered in a context of caring and in a supportive organizational culture, the highest quality of care and best patient outcomes can be achieved.The purpose of this series is to give nurses the knowledge and skills they need to implement EBP consistently, one step at a time. Articles will appear every two months to allow you time to incorporate information as you work toward implementing EBP at your institution. Also, we've scheduled "Chat with the Authors" calls every few months to provide a direct line to the experts to help you resolve questions. Details about how to participate in the next call will be published with September's Evidence-Based Practice, Step by Step. PMID- 20574205 TI - Putting patients first: Partnering with patients' families. AB - This is the sixth in a series of articles from Planetree, an international nonprofit organization founded in 1978 that's "committed to improving medical care from the patient's perspective." For more information, go to www.planetree.org. PMID- 20574206 TI - Uniting States, sharing strategies: Mississippi addresses the nursing shortage. PMID- 20574207 TI - Diabetes under control: Meter, meds, meals, move, and more. AB - A simple bedside approach to teaching diabetes self-management. PMID- 20574213 TI - Using the glycemic index in diabetes management. AB - Consider carbohydrate quality to achieve blood glucose control. PMID- 20574214 TI - Two nurses-one old, one new. AB - A mother's example counts for a lot when the tables are turned. PMID- 20574215 TI - Robert M. Goldwyn, MD: A memorial in his own words. PMID- 20574218 TI - Versatility of free SCIA/SIEA flaps in head and neck defects. AB - Reconstruction of head and neck defects may require replacement of the bony structures, external soft tissue, and intraoral mucosa. Most cases, including maxillary defects, often require repair using only soft tissue flaps. Recently, the authors used free superficial circumflex iliac artery/superficial inferior epigastric (SCIA/SIEA) flaps for head and neck reconstruction. This was their first choice over other free flaps due to its versatile advantages. Fifteen patients underwent head and neck reconstruction with free SCIA/SIEA flaps (n = 16). No flap loss was observed; however, emergency vascular reanastomosis was performed in 3 cases to restore the blood supply in compromised flaps. Flap thinning and secondary debulking procedures were performed in 4 cases. The functional and aesthetic results were deemed as acceptable in all patients. Based on our results, we believe that the free SCIA/SIEA flap is useful for soft tissue defect reconstruction in the head and neck. It has the following advantages: (1) Large flap elevation is possible for reaching distant recipient vessels, (2) Two surgical teams may work at the same time preparing the donor and recipient regions, and (3) The flap design uses an abdominoplasty incision, which has minimal donor site morbidity. PMID- 20574219 TI - Anatomic study of the nostril sill: classification and histologic findings. AB - To define and investigate the normal nostril sill anatomy and classify the different forms.Photographs of the nose of 95 Korean adults and 26 preserved cadavers were studied. Classification of the different forms and cadaveric dissections and histologic studies were performed. Morphologically the noses were studied and classified into 3 types, and histologically the thickness of the soft tissue and muscle layers were measured at the nostril sill.The nostril sill was defined as the soft tissue bulge between 4 borders; medially the foot plate of the columella, laterally the ala, cephalically the vestibule, and caudally the upper lip, and classified into 3 forms. Type I: full nostril sill (55.7%), type II: point nostril sill (31.9%), and type III: flat nostril sill (12.1%). On histologic analysis, in type I, the sill consisted of fibro fatty tissue composed of a mixture of dermal collagen and gland which were thicker at the area of the sill. Also the muscle fibers beneath the sill were more protuberant in this area. The thickness of the soft tissue and muscle layers were significantly thicker at the sill area than the upper lip and vestibule. In types II and III, dermal thickening was not observed and the soft tissue thickness remained unchanged from the upper lip to the nasal vestibule. The muscle fibers showed no protuberance under the sill.This study provides references which will allow more accurate and proper correction and reconstruction of the nose and nostril sill. PMID- 20574220 TI - Modified lateral canthal incision. PMID- 20574223 TI - Hydrogen sulfide in lung injury: therapeutic hope from a toxic gas? PMID- 20574225 TI - Nevius' 1894 discovery of modern anesthesia. PMID- 20574227 TI - Inhaled hydrogen sulfide protects against ventilator-induced lung injury. AB - BACKGROUND: Mechanical ventilation still causes an unacceptably high rate of morbidity and mortality because of ventilator-induced lung injury (VILI). Therefore, new therapeutic strategies are needed to treat VILI. Hydrogen sulfide can induce hypothermia and suspended animation-like states in mice. Hydrogen sulfide can also confer antiinflammatory and antiapoptotic effects. This study investigates the organ-protective effects of inhaled hydrogen sulfide during mechanical ventilation. METHODS: Mice were ventilated with a tidal volume of 12 ml/kg body weight for 6 h with synthetic air in the absence or presence of hydrogen sulfide (80 parts per million) and, in a second series, at either mild hypothermia or normothermia. Staining of lung sections determined the degree of lung damage by VILI score and apoptotic cells. Bronchoalveolar lavage fluid was analyzed for the cytokines interleukin-1beta and macrophage inflammatory protein 1beta and for neutrophil accumulation. Heme oxygenase-1 and heat shock protein 70 expression were assessed in the lung tissue by Western immunoblot analysis. RESULTS: Mechanical ventilation at both hypothermia and normothermia led to a profound development of VILI, characterized by pulmonary edema, increased apoptosis, cytokine release, neutrophil recruitment, and up-regulation of the stress proteins such as heme oxygenase-1 and heat shock protein 70. In contrast, the application of hydrogen sulfide during ventilation at either mild hypothermia or normothermia prevented edema formation, apoptosis, proinflammatory cytokine production, neutrophil accumulation, and inhibited heme oxygenase-1 expression. CONCLUSIONS: Inhalation of hydrogen sulfide during mechanical ventilation protects against VILI by the inhibition of inflammatory and apoptotic responses. Hydrogen sulfide confers lung protection independently of its ability to induce mild hypothermia during ventilation. PMID- 20574231 TI - Don't patients have two knees? PMID- 20574232 TI - Staggered bilateral knee arthroplasty: good or bad? PMID- 20574234 TI - Is GlideScope the best way to intubate? PMID- 20574235 TI - Postoperative opioids remain a serious patient safety threat. PMID- 20574238 TI - Herpetic epithelial keratitis after intravitreal injection of bevacizumab. PMID- 20574240 TI - Update on the pathophysiology of obesity. PMID- 20574241 TI - The enigma of catabolism. PMID- 20574243 TI - Current Opinion in Clinical Nutrition and Metabolic Care. Current world literature. PMID- 20574242 TI - Carbohydrate and exercise performance: the role of multiple transportable carbohydrates. AB - PURPOSE OF REVIEW: Carbohydrate feeding has been shown to be ergogenic, but recently substantial advances have been made in optimizing the guidelines for carbohydrate intake during prolonged exercise. RECENT FINDINGS: It was found that limitations to carbohydrate oxidation were in the absorptive process most likely because of a saturation of carbohydrate transporters. By using a combination of carbohydrates that use different intestinal transporters for absorption it was shown that carbohydrate delivery and oxidation could be increased. Studies demonstrated increases in exogenous carbohydrate oxidation rates of up to 65% of glucose: fructose compared with glucose only. Exogenous carbohydrate oxidation rates reach values of 1.75 g/min whereas previously it was thought that 1 g/min was the absolute maximum. The increased carbohydrate oxidation with multiple transportable carbohydrates was accompanied by increased fluid delivery and improved oxidation efficiency, and thus the likelihood of gastrointestinal distress may be diminished. Studies also demonstrated reduced fatigue and improved exercise performance with multiple transportable carbohydrates compared with a single carbohydrate. SUMMARY: Multiple transportable carbohydrates, ingested at high rates, can be beneficial during endurance sports in which the duration of exercise is 3 h or more. PMID- 20574244 TI - Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials. AB - BACKGROUND: Results of randomized controlled trials are consistent in showing reduced rates of stroke, heart failure and cardiovascular events in very old patients treated with antihypertensive drugs. However, inconsistencies exist with regard to the effect of these drugs on total mortality. METHODS: We performed a meta-analysis of available data on hypertensive patients 80 years and older by selecting total mortality as the main outcome. Secondary outcomes were coronary events, stroke, cardiovascular events, heart failure and cause-specific mortality. The common relative risk (RR) of active treatment versus placebo or no treatment was assessed using a random-effect model. Linear meta-regression was performed to explore the relationship between intensity of antihypertensive therapy and blood pressure (BP) reduction and the log-transformed value of total mortality odds ratios (ORs). RESULTS: The overall RR for total mortality was 1.06 (95% confidence interval 0.89-1.25), with significant heterogeneity between hypertension in the very elderly trial (HYVET) and the other trials. This heterogeneity was not explained by differences in the follow-up duration between trials. The meta-regression suggested that a reduction in mortality was achieved in trials with the least BP reductions and the lowest intensity of therapy. Antihypertensive therapy significantly reduced (P < 0.001) the risk of stroke (35%), cardiovascular events (27%) and heart failure (50%). Cause-specific mortality was not different between treated and untreated patients. CONCLUSION: Treating hypertension in very old patients reduces stroke and heart failure with no effect on total mortality. The most reasonable strategy is the one associated with significant mortality reduction; thiazides as first-line drugs with a maximum of two drugs. PMID- 20574245 TI - Blood pressure lowering in the oldest old. PMID- 20574246 TI - Adiposity and hypertension: the inflammatory link. PMID- 20574247 TI - Antihypertensive treatment in patients with cerebrovascular disease: the lower the better? PMID- 20574248 TI - More complete renin-angiotensin system blockade: better outcomes or smoke and mirrors. PMID- 20574250 TI - Evening administration of antihypertensive drugs: filling a knowledge gap. PMID- 20574249 TI - Reduced cerebrovascular remodeling and functional impairment in spontaneously hypertensive rats following combined treatment with suboptimal doses of telmisartan and ramipril: is less really more? PMID- 20574251 TI - The potential yield of ECG screening of hypertensive patients: the Utrecht Health Project. AB - OBJECTIVE: Several guidelines for hypertension and cardiovascular risk management recommend an ECG in hypertensive patients to improve risk prediction. We estimated the prevalence of clinically relevant ECG abnormalities and the number needed to screen (NNS) with a routine ECG to prevent the occurrence of one death in the next 10 years conditional on adequate treatment and follow-up. METHODS: The study population consisted of 866 hypertensive participants recruited from the Utrecht Health Project (UHP), a dynamic population study in Utrecht. Baseline measurements included an ECG and the risk factors that enable a Systematic COronary Risk Evaluation (SCORE) risk estimation for each participant. ECGs were interpreted using Modular ECG Analysis System for computerized recognition of ECG abnormalities. NNS to prevent one death was computed by the reciprocal of the prevalence of the ECG abnormalities multiplied by number needed to treat to prevent one death when the ECG abnormality is managed according to the prevailing clinical guidelines. RESULTS: The population consisted of 54.2% men with a mean age of 53.2 years (SD 11.5). The prevalence of ECG abnormalities was 17.6 [n = 95% confidence interval (CI) 15.0-20.1]. Prevalence of atrial fibrillation or prior myocardial infarction was 2.1% (95%CI 1.1-3.0) and of other ECG abnormalities related to increased cardiovascular disease risk 15.4% (95%CI 13.1 17.9). NNS to prevent one death from cardiovascular disease within 10 years was estimated at 260 (95%CI 220-308). CONCLUSION: Our findings support the existing recommendations to routinely record an ECG in unselected hypertensive patients as the prevalence of relevant abnormalities is considerable and NNS to prevent one death is lower than that in other widely accepted tests. PMID- 20574252 TI - The effect of crossing legs on blood pressure. PMID- 20574253 TI - Agreement within Europe about antihypertensive treatment and education - results from the European Society of Hypertension questionnaire. PMID- 20574255 TI - Escalators, rubber clogs, and severe foot injuries in children. AB - BACKGROUND: Reports in the media suggest that escalator-related foot injuries are on the rise. Trendy, bright-colored rubber clogs have been implicated in a significant number of these incidents involving children. We review the children who sustained severe foot injuries on escalators, were wearing rubber clogs at the time of injury, and who were admitted to hospital for emergency surgery. METHODS: A list of children who sustained foot injuries on escalators was generated from the hospital database and included for study. From clinical chart review, demographic data, footwear type, and injuries sustained were recorded. Inpatient or outpatient treatment rendered was also recorded for each patient. RESULTS: Between September 2006 and September 2008, we treated 17 children for escalator-related foot injuries. There were 10 boys and 7 girls who were between 2 and 9 years of age (mean: 5.5). Thirteen children (76.5%) from this group were wearing rubber clogs at the time of injury. Nine of these 13 (69.2%) children sustained severe foot injuries that required admission to hospital for emergency surgery and are the focus of this study. One child had an unsalvageable traumatic amputation of the great toe at the level of the interphalangeal joint. Two children sustained crush injuries to the great toe: 1 with severe degloving and the other with an open fracture of the proximal phalanx. One child had an open fracture-dislocation of the second metatarsophalangeal joint with a comminuted fracture of the second metatarsal. Five children sustained multiple deep lacerations in the foot and 2 of them had associated cut tendons that required repair. In the group not wearing rubber clogs, 3 of 4 children had severe foot injuries. In this series, 4 children with rubber clogs and another child with a different footwear sustained minor injuries; they were treated as outpatients. CONCLUSIONS: Escalator-related foot injuries involving rubber clogs can result in severe crushing of the foot and even traumatic amputation. The broad toe-box design may give a false perception of the distance between the foot and the side of the escalator, whereas the 'softness' of these rubber clogs makes them vulnerable to crush by moving escalator steps. This is the first report in the literature describing escalator-related severe foot injuries in children who were wearing rubber clogs. Injuries sustained can be significant and permanent. The potential dangers of escalators and rubber clogs must not be underestimated. LEVEL OF EVIDENCE: Level IV, Case Series. PMID- 20574256 TI - Single bone intramedullary fixation of the ulna in pediatric both bone forearm fractures: analysis of short-term clinical and radiographic results. AB - BACKGROUND: Although single bone intramedullary (IM) fixation has been advocated in the treatment of unstable diaphyseal forearm fractures, some reports have questioned the ability of single bone fixation to maintain adequate reduction. The purpose of this investigation is to report the radiographic and early clinical results of single bone IM fixation for diaphyseal forearm fractures and to identify factors leading to loss of reduction of the radius after ulnar fixation. METHODS: A retrospective analysis of 38 children who underwent single bone IM fixation of the ulna for both bone forearm fractures was performed. Mean age was 9 years (range: 4-14 y). Preoperative, postoperative, and final follow-up radiographs were examined for radiographic alignment. Patient data (including age, fracture type, delay to fixation, open vs. percutaneous reduction and fixation, and time to implant removal) was collected to identify predictors for loss of reduction of the radius. Loss of reduction of the radius was defined as 10 degrees or greater change of angulation in either the frontal or lateral plane from initial postoperative radiographs to final follow-up. Multivariate analysis was used to determine associations between patient factors and loss of reduction. RESULTS: All patients went on to bony union with restoration of forearm rotation. Twenty-five patients (66%) healed with <10 degrees of angulation of the radius, whereas 11 patients (29%) had between 10 and 20 degrees of angulation at final follow-up. Two patients demonstrated greater than 20 degrees of radial angulation requiring additional surgical care. There was no statistically significant association between any patient factors and loss of radial reduction, though there was a trend for increased radial angulation in patients who had sustained open fractures. CONCLUSIONS: Single-bone IM fixation of the ulna is a safe and efficacious option for the treatment of unstable diaphyseal forearm fractures in children. Owing to the increased risk of loss of radial reduction, however, consideration should be made for IM fixation of both bones in older children and cases of open fractures. LEVEL OF EVIDENCE: IV, therapeutic. PMID- 20574257 TI - Clinical and radiographic results of lateral condylar fracture of distal humerus in children. AB - BACKGROUND: The treatment goal in lateral condylar fracture is union without residual deformity. However, growth disturbance may occur despite initial anatomic reduction and secure fixation. The purpose of this study was to evaluate the clinical and functional results, including complications, of lateral condylar fracture treatments in children, and to identify differences between treatment methods. METHODS: One hundred seventy-five patients followed for more than a year with available initial and final follow-up radiographs were included. Carrying angle and range of motion limitations were assessed, and functional results were evaluated using the scoring system devised by Dhillon et al. All complications including varus, valgus, lateral overgrowth, fishtail deformity, nonunion, malunion, and avascular necrosis were investigated statistically. RESULTS: There were 113 male and 62 female of mean age 4 years 9 months. Thirty-nine patients were managed by cast immobilization. Closed reduction and internal fixation (CRIF) was carried out in 33 and open reduction and internal fixation (ORIF) in 103. Kirschner wires were removed at a mean 5.5 weeks. There were 11 superficial infections, 3 valgus, 3 delayed unions. In 135 (77.1%) of the 175 patients, obvious lateral condylar overgrowths were observed at 19.8 (+/-16.8) months (range, 12 to 120) without evidence of a functional abnormality. Development of lateral elbow prominence revealed difference between the 3 treatment methods and it was caused by the difference between cast and ORIF (1 vs. 32, P<0.001). It also showed difference between the 3 fracture types and it was caused by significant difference between type I and II (1 vs. 24) and between I and III (1 vs. 14) (P<0.001, respectively). Mean radiographic carrying angles showed a decrease of 5.0 (+/-4.6) degrees at final follow-ups, but no significant difference was observed between fracture types or treatment method (P=0.832 and 0.850, respectively). Clinically, 17 cases (9.7%) with varus deformities were observed, although there was no need for corrective surgery. At final follow-ups, 116 patients had achieved an excellent result and 59 a good result. CONCLUSION: This study shows that bone union and good clinical results can be achieved in children with a lateral condylar fracture, and that lateral overgrowth and cubitus varus are the most common residual deformities. Furthermore, these residual deformities were not remodeled at a mean 19.8 months after injury. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 20574258 TI - Iatrogenic ulnar nerve injury after the surgical treatment of displaced supracondylar fractures of the humerus: number needed to harm, a systematic review. AB - BACKGROUND: Supracondylar fractures of the humerus are common pediatric elbow injuries. Most displaced or angulated fractures are treated by closed reduction and percutaneous pinning, with either a crossed pin or lateral pin configuration. The purpose of this study was to conduct a systematic review to determine if there is an increased risk of iatrogenic nerve injury associated with the crossed pin configuration. METHODS: Relevant articles were identified by searching electronic databases and hand searching-related journal and conference proceedings. Within each trial, the risk of iatrogenic ulnar nerve injury was calculated for each pinning technique. For studies comparing crossed versus lateral pinning, the resulting trial-based differences in risk estimates were pooled using a random effects meta-analysis. A number needed to harm was determined using the pooled risk difference. RESULTS: Thirty-two trials consisting of 2639 patients were used in the pooled analysis. The pooled risk difference of iatrogenic ulnar nerve injury is 0.035 (95% confidence interval, 0.014-0.056), with a higher incidence of injury in the crossed pinning group. The weighed number needed to harm for the crossed pinning is 28 (95% confidence interval, 17-71). CONCLUSIONS: The results of this review suggest that there is an iatrogenic ulnar nerve injury for every 28 patients treated with the crossed pinning compared with the lateral pinning. Further research is necessary to ensure that the optimal pinning technique is chosen to treat these factors. LEVEL OF EVIDENCE: Level III. PMID- 20574259 TI - Results of Pavlik harness treatment in children with dislocated hips between the age of six and twenty-four months. AB - BACKGROUND: We retrospectively studied the outcome of Pavlik harness treatment in late-diagnosed hip dislocation in infants between 6 and 24 months of age (Graf type 3 and 4 or dislocated hips on radiographs) treated in our hospital between 1984 and 2004. The Pavlik harness was progressively applied to improve both flexion and abduction of the dislocated hip. In case of persistent adduction contracture, an abduction splint was added temporarily to improve the abduction. METHODS: We included 24 patients (26 hips) between 6 and 24 months of age who presented with a dislocated hip and primarily treated by Pavlik harness in our hospital between 1984 and 2004. The mean age at diagnosis was 9 months (range 6 to 23 mo). The average follow-up was 6 years 6 months (2 to 12 y). Ultrasound images and radiographs were assessed at the time of diagnosis, one year after reposition and at last follow-up. RESULTS: Twelve of the twenty-six hips (46%) were successfully reduced with Pavlik harness after an average treatment of 14 weeks (4 to 28 wk). One patient (9%) needed a secondary procedure 1 year 9 months after reposition because of residual dysplasia (Pelvis osteotomy). Seventeen of the 26 hips were primary diagnosed by Ultrasound according to the Graf classification. Ten had a Graf type 3 hip and 7 hips were classified as Graf type 4. The success rate was 60% for the type 3 hips and 0% for the type 4 hips. (P=0.035). None of the hips that were reduced with the Pavlik harness developed an avascular necrosis (AVN). Of the hips that failed the Pavlik harness treatment, three hips showed signs of AVN, 1 after closed reposition and 2 after open reposition. CONCLUSION: The use of a Pavlik harness in the late-diagnosed hip dislocation type Graf 3 can be a successful treatment option in the older infant. We have noticed few complications in these patients maybe due to progressive and gentle increase of abduction and flexion, with or without temporary use of an abduction splint. The treatment should be abandoned if the hips are not reduced after 6 weeks. None of the Graf 4 hips could be reduced successfully by Pavlik harness. This was significantly different from the success rate for the Graf type 3 hips. LEVEL OF EVIDENCE: Therapeutic study, clinical case series: Level IV. PMID- 20574260 TI - Initial stability of the acetabular fragment after periacetabular osteotomy: a biomechanical study. AB - BACKGROUND: Periacetabular osteotomy (PAO) has become the treatment of choice for skeletally mature patients with symptomatic acetabular dysplasia. Coincident with increasing use of PAO worldwide has been the introduction of various techniques for fixation of the acetabular fragment. Owing to the expanding indications for PAO, such as acetabular retroversion and femoroacetabular impingement, there is an increased interest in biomechanical data supporting the use of the varied acetabular fragment fixation techniques. Our study investigated the biomechanical strength of several PAO fixation techniques in vitro, including a novel plating technique. METHODS: PAO was performed on 17 artificial hemi-pelves with standardized biomechanical properties. Specimens were instrumented with the following constructs-3 screws from the iliac crest into the fragment (IS), 3 screws from the iliac crest and 1 transverse screw from the anterior inferior iliac spine into the sciatic buttress (IT), or 1 transverse screw with a contoured 3-hole plate across the iliac osteotomy (PT). The specimens were then loaded cyclically under compression and tension and to failure under tension in an material testing system through the anterior-inferior iliac spine. RESULTS: Data analysis with a single factor analysis of variance yielded mean loads-to failure of 462 N for IS, 714 N for IT, and 817 N for PT (P=0.005). Further analysis using 2-sample t tests revealed that both IT and PT provided significantly higher loads-to-failure than IS (P=0.016 and P=0.0007, respectively). Under cyclic compression loading, the IT construct demonstrated decreased overall displacement when compared with IS (P=0.003). Under cyclic tension loading, PT achieved significantly smaller overall displacement than IS (P=0.007), as did IT when compared with IS (P=0.018). However, no significant difference was found between PT and IT (P=0.165) groups in cyclic loading or failure testing. CONCLUSIONS: Prior results showing improved performance of the IT construct have been replicated in a novel tension model. The novel plating technique provides greater load-to-failure than IS and is not inferior to IT. Both PT and IT allow significantly less displacement than IS in tensile and compressive cyclic loading. This novel technique may be easier to perform by surgeons in training or those new to the procedure. The results suggest a move beyond fixation solely with 3 antegrade screws. LEVEL OF EVIDENCE: Biomechanical study. PMID- 20574261 TI - Surgical decompression for lumbar stenosis in pediatric achondroplasia. AB - BACKGROUND: Spinal stenosis is a common complication of achondroplasia. To our knowledge, no study has evaluated a greater than 2-year outcome after surgical intervention for spinal stenosis in such children or compared decompression with and without instrumentation in relation to revision surgery. Our purpose was to assess the efficacy of lumbar decompression and instrumentation for symptomatic stenosis in children with achondroplasia. METHODS: We retrospectively reviewed our institution's database to identify children (< or =18 y old) with achondroplasia undergoing initial spinal decompression for lumbar stenosis from 1995 through 2003. We identified 18 such patients and reviewed their medical records for demographic data, presenting signs and symptoms, and treatment and outcome data. Mean follow-up was 72.0+/-27.6 months. We determined each patient's symptom score (SS) based on presence of leg weakness, numbness, or pain; abnormal reflexes; incontinence; and walking intolerance (unable to walk > or =5 blocks). Each finding was scored 1 point (6 points maximum). Nine patients requiring revision surgery were assigned a revision postoperative SS. All patients were contacted at the end of data collection and assigned a final follow-up SS. Baseline SS values were compared with postoperative, revision postoperative, and final follow-up scores using a paired t test (alpha=0.05). RESULTS: The mean preoperative and final SS values were significantly different: 4.0+/-0.9 (most common symptoms, leg weakness and incontinence) and 1.6+/-1.7 (most common symptom, leg weakness), respectively. Nine patients underwent decompression with instrumentation initially; 9 did not; 7 of the latter required instrumentation during revision; and 2 of the former also required revision. Those without initial instrumentation were 3.5 times more likely (odds ratio=12.3) to require revision. CONCLUSIONS: Surgical decompression with instrumentation significantly reduced the symptoms of lumbar stenosis and the likelihood of revision surgery in children with achondroplasia. LEVEL OF EVIDENCE: Level III therapeutic study. PMID- 20574263 TI - MRI pathoanatomy study of congenital vertical talus. AB - BACKGROUND: Prior reports regarding the pathologic anatomy for congenital vertical talus have noted some disagreement as to which elements of the pathologic anatomy are consistently present. The purpose of his study is to evaluate the 3-dimensional morphologic changes and pathoanatomy of the congenital vertical talus using magnetic resonance imaging. METHODS: Nine patients with congenital vertical talus (ranging from 5 mo-11 y) underwent magnetic resonance imaging of both feet. A foot and ankle coil was used for the 1.5 T system. The protocol consisted of T1-weighted spin echo sequence image and T2-weighted fast spin echo sequence image in the sagittal, coronal, and axial planes. Slice thickness ranged from 3 to 4 mm with 0 to 1.0 mm interspace thickness. A descriptive analysis was performed based upon the T1-weighted image by physicians. RESULTS: At the level of the talonavicular joint, the navicular was seen significantly subluxed dorsally with associated wedging of the navicular. At the level of the calcaneocuboid joint, often there was a significant dorsal subluxation of the cuboid in relation to the calcaneus. Lateral obliquity of the calcaneocuboid joint could be present to varying degrees. The anterior calcaneus was significantly laterally displaced in relation to the talar head with an element of lateral translation and eversion of the calcaneus at the subtalar joint. Distal cavus at the cuneiform-first metatarsal joint was observed in 5 patients. CONCLUSIONS: This study suggests that there is significant pathology at the level of subtalar joint in congenital vertical talus. In addition to satisfactory reduction of the talonavicular joint, methods to ensure realignment of the calcaneus under the talus may be a crucial component of deformity correction and to prevent recurrence of deformity. LEVEL OF EVIDENCE: A Level III diagnostic study using normal pediatric foot anatomy in magnetic resonance imaging as a reference. PMID- 20574264 TI - All-epiphyseal semitendinosus PCL reconstruction in a 10-year-old child. AB - BACKGROUND: Tears of the posterior cruciate ligament (PCL) in pediatric patients, especially avulsions from its tibial insertion, are not frequently encountered by physicians. However, with an increasing incidence of ligamentous injuries to the knee in skeletally immature patients, orthopaedic surgeons will more frequently need to decide how best to manage a PCL injury in children with open physes. METHODS: A 10-year-old boy sustained an avulsion of the PCL from its tibial insertion site after a bicycle motocross racing accident. He required a PCL reconstruction after failed conservative treatment and an unsuccessful attempt at primary repair. This successful physeal sparing reconstruction was accomplished using a modified method of femoral tunnel placement in combination with the tibial inlay technique. RESULTS: A magnetic resonance imaging was acquired 2 years postoperatively when physical examination demonstrated both legs of equal length, no varus or valgus deformity, and a normal posterior drawer examination. Four years after the reconstruction, he continues to bicycle motocross race while experiencing no further symptoms and complete restoration to his prior quality of life. CONCLUSIONS: The use of the tibial inlay technique together with the modified femoral tunnel location prevented transphyseal drilling while attaining a favorable anatomic placement of the graft while avoiding the "killer" turn associated with the transtibial approach. LEVEL OF EVIDENCE: Level IV (Therapeutic Study). PMID- 20574262 TI - Epidural pneumatosis of the cervicothoracic spine associated with transient upper motor neuron findings complicating Haemophilus influenzae pharyngitis, bronchitis, and mediastinitis. AB - BACKGROUND: Epidural pneumatosis and pneumomediastinum are rare findings. Reports in children are exceedingly rare. Abnormal neurologic findings have yet to be reported. METHODS: We report on the case of a 7-year-old girl who was diagnosed with epidural pneumatosis with signs of neurologic compression in the setting of Haemophilus influenzae upper and lower respiratory infection. After urgent direct laryngoscopy, bronchoscopy, esophagoscopy, and pharyngeal biopsy was carried out, CT scan of the chest revealed extensive pneumomediastinum tracking along vessels throughout the neck and chest in addition to epidural pneumatosis from C6 to T5. Upper motor neuron findings were present. Broad spectrum antibiotics were administered, and interval neurologic examination and repeat CT scans showed resolution of abnormal neurologic exam in addition to epidural pneumatosis dissipation. RESULTS: Rapid clinical improvement was noted on broad spectrum intravenous antibiotics with extubation on postoperative day one. She was discharged home on oral augmentin on postoperative day 4 with intact neurologic examination. At 11 month follow-up, she remained symptom-free with normal neurologic examination and unremarkable cervical and thoracic spine radiographs. CONCLUSION: Resolution of clinical and radiographic findings is possible with conservative treatment. LEVEL OF EVIDENCE: IV. PMID- 20574265 TI - Shoulder function after medial approach and derotational humeral osteotomy in patients with brachial plexus birth palsy. AB - BACKGROUND: The purpose of this study was to assess outcome after rotational humeral osteotomies, using a medial approach, in children with brachial plexus birth palsy. METHODS: A retrospective review of children with brachial plexus birth palsy who underwent external rotational humeral osteotomies, using a medial approach, for the treatment of internal rotation contractures was performed. Presurgical and postsurgical range of motion, standard Mallet, and modified Mallet scores were recorded. The traditional Mallet score was modified to include a sixth subscale that further evaluated internal rotation. This was assessed by having the patients' attempts to place their palm flat on their naval. RESULTS: Twenty-three children underwent external rotational humeral osteotomies. The mean rotational correction achieved during the procedure was 43.2+/-11.6 degrees (range: 20-70 degrees). The mean preoperative standard aggregate Mallet score was 13.8+/-2.8 and the mean postoperative score was 16.1+/-2.5 (P=0.002). When the additional internal rotation scale was added into the score, the mean preoperative aggregate score was 18.0+/-2.1 and the mean postoperative score was 19.5+/-2.8 (P=0.032). Further analysis revealed a statistically significant improvement (P<0.05) in external rotation, hand to neck, and hand to mouth functions. Internal rotation was decreased as represented by statistically significant decreases in hand to spine and hand to belly (P<0.05). CONCLUSIONS: Rotational humeral osteotomies can be performed safely and effectively using a medial approach. These osteotomies significantly improve activities associated with external rotation. However, the degree of external rotation must be carefully balanced against the loss of internal rotation, which would impede midline function. The addition of a sixth subscale to the Mallet score that assesses hand to belly provides more clinically relevant information regarding midline function than hand to spine. LEVEL OF EVIDENCE: This is a Level IV study. PMID- 20574267 TI - Achilles tendon length and medial gastrocnemius architecture in children with cerebral palsy and equinus gait. AB - BACKGROUND: The aim of this study was to examine both the tendon and muscle components of the medial gastrocnemius muscle-tendon unit in children with cerebral palsy (CP) and equinus gait, with or without contracture. We also examined a small number of children who had undergone prior surgical lengthening of the triceps surae to address equinus contracture. METHODS: Ultrasound was used to measure Achilles tendon length and muscle-tendon architectural parameters in children of ages 5 to 12 years. Muscle and tendon parameters were compared among 4 groups: Control group (N=40 limbs from 21 typically developing children), Static Equinus group (N=23 limbs from 15 children with CP and equinus contracture), Dynamic Equinus group (N=12 limbs from 7 children with CP and equinus gait without contracture), and Prior Surgery group (N=10 limbs from 6 children with CP who had prior gastrocnemius recession or tendo-achilles lengthening). The groups were compared using analysis of variance and Scheffe post hoc tests. RESULTS: The CP groups had longer Achilles tendons and shorter muscle bellies than the Control group (P<0.001). Normalized tendon length was also longer in the Prior Surgery group compared with the Static Equinus group (P<0.001). The Prior Surgery group had larger pennation angles than the CP groups (P< or =0.009) and tended to have shorter muscle fascicle lengths (P< or =0.005 compared with Control and Static Equinus, P=0.08 compared with Dynamic Equinus). Similar results were observed for pennation angles and normalized muscle fascicle lengths throughout the range of motion. CONCLUSIONS: Children with spastic CP and equinus gait have longer-than-normal Achilles tendons and shorter-than-normal muscle bellies. These characteristics are observed even in children with dynamic equinus, before contracture has developed. Surgery further lengthens the tendon, restoring dorsiflexion but not normal muscle-tendon architecture. These architectural features likely affect function, possibly contributing to functional deficits such as plantarflexor weakness after surgery. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 20574266 TI - Dynamic displacement of the femoral head by hamstring stretching in children with cerebral palsy. AB - BACKGROUND: Hamstring stretching is an integral component in the treatment for knee flexion contracture in cerebral palsy (CP). As hamstrings span across hip and knee joints, passive stretching of hamstrings applies force to the hip that is often dysplasia in CP. The purpose of this study is to measure the dynamic displacement of femoral head produced by passive stretching of hamstrings and to determine the factors associated with the phenomenon. METHODS: Children with spastic CP were studied using computerized tomography (CT) of the pelvis. Two sets of CT studies were carried out, one with the knee flexed and the hip flexed (resting) and the other with the knee extended and the hip flexed to simulate manual hamstrings stretching. The distance from pelvic baseline to the posterior margin of femoral epiphysis was measured on the CT images and compared between resting and stretching for dynamic displacement. The dynamic displacement of the femoral head was expressed by a ratio to femoral epiphysis diameter. RESULTS: Twenty-seven CP children had CT studies at a mean age of 6.8 years (range: 4.5 to 9.6 y). Ten children were ambulators with or without devices and the other 17 children were nonambulators. On plain radiographs of the pelvis, the mean Reimer's migration percentage was 39% (range: 13% to 92%). On CT scan, dynamic displacement by stretching was 4.7% (range: -3.8% to 16.1%) of femoral epiphysis diameter (P<0.001 by paired t test). The displacement in the 33 hips with migration percentage of greater than 30% was significantly greater than the displacement in the other 21 hips with migration percentage of less than 30% (7.4% vs. 0.5%, P=0.001). CONCLUSIONS: Passive stretching of spastic hamstrings in the hip flexion position resulted in dynamic posterior displacement of the femoral head. Medical professionals should be aware of this fact, especially in spastic CP children with a higher migration percentage on radiograph. LEVEL OF EVIDENCE: Diagnostic II. PMID- 20574269 TI - Issues of concern before single event multilevel surgery in patients with cerebral palsy. AB - BACKGROUND: This study was performed to identify the issues of concern of parents of patients with cerebral palsy before single event multilevel surgery (SEMS). METHODS: The parental concerns of 64 patients [34 males, 30 females, mean age 15 y and 5 mo (SD 8 y and 10 mo)] with cerebral palsy were obtained using a questionnaire preoperatively. The issues of parental concern were evaluated using 59 items specifically designed for this study. The individual items were scored using a 5-point Likert scale (1 to 5). RESULTS: The top 5 issues of concern were as follows: postoperative rehabilitation, duration of rehabilitation, immediate postoperative pain, general anesthesia, and medical cost. Sporting activities and poor compliance to wearing orthosis were included in the top 5 issues of parental concern in patients with unilateral involvement. The overall parental concern in patients with unilateral involvement was lower than that in bilateral involvement (P=0.054). Parents of younger patients showed significantly higher concern score than those of older patients (P=0.020). There was no significant difference in the overall concern score between the parents of patients scheduled for bony procedures and those of patients scheduled for soft tissue procedures (P=0.298). Multiple regression analysis revealed the patient's age (P=0.018) and responding parent (father vs. mother, P=0.025) to be the factors that significantly affected the overall concern score (adjusted R(2)=0.281). CONCLUSIONS: An understanding of the issues of concern will enhance communication between physicians and parents, which would assist in preoperative discussion. LEVEL OF EVIDENCE: Diagnostic level II. PMID- 20574268 TI - Is percutaneous adductor tenotomy as effective and safe as the open procedure? AB - BACKGROUND: Percutaneous adductor longus tenotomy (PAT) is a frequently used procedure, yet no study has ever compared its effectiveness and safety with those of open adductor longus tenotomy (OAT). We conducted this prospective study to describe the effects of PAT and to compare them with those of OAT. METHODS: This consisted of a cross-over randomized controlled trial including 50 consecutive hips from 27 patients with cerebral palsy scheduled for adductor tenotomy in the setting of multilevel tendon lengthening/release procedures or hip surgery (femoral or Dega osteotomy) in a university hospital. A pediatric orthopaedic surgeon conducted a PAT. Another surgeon extended the wound to explore what had been cut during the PAT, and completed the tenotomy if necessary. Hip abduction (HA) was assessed by a third surgeon immediately before PAT, after PAT, and then after OAT, using a goniometer, in a standardized reproducible manner. All 3 surgeons were blinded to the others' findings. Primary end-points included the percentage of tendon/muscle portion sectioned percutaneously, and the HA measure. Comparison between HA after PAT and OAT was done using a paired t-test with a 95% confidence interval. The influence of anatomic variants of adductor longus origin was also assessed. RESULTS: Mean HA (hips flexed) measured 40.36 degrees preoperatively and increased to 50.04 degrees after PAT (P<0.0001). After OAT, HA averaged 53.32 degrees with no statistical gain compared with that observed after PAT (P=0.2). The tendinous portion of adductor longus was cut to an average of 98% by PAT (completely in 46 cases and more than 75% in only 4 cases). The muscular portion of adductor longus origin was cut to an average of 83.7% (completely in only 15 cases, cut to more than 75% in 26 cases, and approximately 50% in 9 cases). The gain in HA positively correlated with the extent of the tendinous portion divided (P=0.03) but not with the extent of muscular portion divided. Results were independent of the anatomic variants of adductor longus origin. Partial section of adductor brevis after PAT was encountered in 6 cases. No major iatrogenic lesion was observed (obturator nerve, major vessels). CONCLUSIONS: This is the only prospective study concerning the effects of PAT. The anatomic factor associated with gain in HA seems to be the extent of the section of the tendinous portion of adductor longus origin, which was found to be cut to more than 90% in all cases after PAT. The extent of muscular portion section does not seem to influence the gain in HA. The researchers detail the technique of percutaneous adductor tenotomy and show that when done correctly, PAT is a fast and simple procedure, as reliable and effective as the open release and without any major risks. LEVEL OF EVIDENCE: Level II therapeutic study prospective comparative study. PMID- 20574270 TI - Evaluation of high-risk patients undergoing spinal surgery: a matched case series. AB - BACKGROUND: Neuromuscular (NM) spinal deformities necessitating surgical intervention present a difficult challenge to the medical community. Underlying comorbidities lead to extended hospital stays, significant complications, and social challenges in the extensive perioperative period. In response to this problem, a therapeutic algorithm, the Care Pathway for Spinal Surgery (CAPSS) has been developed at our institution to address this complex medical issue. METHODS: In 1999, a multidisciplinary team developed a treatment protocol, CAPSS, that emphasized perioperative work up and operative scheduling under the direction of a dedicated care coordinator. A case series analysis was conducted to compare the surgical outcomes from before and after CAPSS implementation. Statistical analyses were performed on a carefully paired subset of NM patients (N=9). Outcome measures were hospital length of stay (LOS), pediatric intensive care unit LOS, number of days intubated, surgical estimated blood loss, postoperative curve magnitude, percent curve correction, and perioperative complications. RESULTS: Statistical analyses indicated that the use of CAPSS provided significant reduction in overall LOS, pediatric intensive care unit LOS, and perioperative complication rate within this patient group. CONCLUSIONS: CAPSS is an effective method to improve perisurgical care within the NM patients with spinal deformity necessitating operative stabilization. LEVEL OF EVIDENCE: III Retrospective comparative study. PMID- 20574271 TI - Analysis of the pediatric orthopedic surgery questions on the Orthopaedic In Training Examination, 2002 through 2006. AB - BACKGROUND: Pediatric orthopedics has been a frequently tested topic on the Orthopaedic In-Training Examination (OITE). Our goal was to provide direction for resident education efforts by: (1) analyzing the exam's number, topics, and types of pediatric orthopedic surgery questions; (2) examining references cited in the postexam answer packet supplied by the American Academy of Orthopaedic Surgeons; and (3) examining the efficacy of the Orthopaedic Knowledge Update (OKU): Pediatrics 3 book as a source for answers to the pediatric orthopedic questions. METHODS: We reviewed 5 years (2002 through 2006) of OITEs and the associated American Academy of Orthopaedic Surgeons' answer packets and assessed the OKU: Pediatrics 3 book for topic relativity. Each question was classified into 1 of 6 categories and labeled with a cognitive taxonomy level: 1 (simple recall), 2 (interpretation of data), or 3 (advanced problem-solving). The 6 categories included: (1) pediatric orthopedic knowledge; (2) knowledge of treatment modalities; (3) diagnosis; (4) diagnosis with recognition of associated conditions; (5) diagnosis with further studies; and (6) diagnosis with treatment. RESULTS: The overall percentage of pediatric questions was 14.1%. The most commonly addressed were pediatric elbow fractures, osteomyelitis, and scoliosis. The most common question types were categories 1 (pediatric orthopedic knowledge) and 6 (diagnosis with treatment). The most frequently referenced textbooks were Lovell and Winter's Pediatric Orthopaedics (31%) and Tachdjian's Pediatric Orthopaedics (16%). The most frequently referenced journals were the Journal of Pediatric Orthopaedics (American) (29%) and the Journal of Bone and Joint Surgery (American) (19%). Using only the OKU: Pediatrics 3 review textbook, 65% of the questions could be answered. CONCLUSIONS: Knowledge of the topics more likely to be tested may help the orthopedic educator direct a didactic curriculum geared toward the OITE and American Board of Surgery examinations. Although the OKU: Pediatrics 3 book seems to be a good, concise resource for studying for the board examination and OITE, residents should be encouraged to supplement their studying with primary sources. LEVEL OF EVIDENCE: Not applicable. PMID- 20574272 TI - Chronic osteomyelitis in children: treatment by intramedullary reaming and antibiotic-impregnated cement rods. AB - BACKGROUND: Chronic osteomyelitis (CO) is rarely encountered in developed countries and is especially rare in children and adolescents. However, on occurrence, it can pose a difficult therapeutic challenge necessitating a combination of aggressive surgical treatment and prolonged antibiotic administration. METHODS: Four patients were treated for CO in the Pediatric Orthopaedic Unit at Schneider Children's Medical Center between June 2005 and December 2006 and were reviewed retrospectively. Surgical treatment consisted of debridement and lavage, reaming of the intramedullary canal and insertion of gentamycin-impregnated polymetamethacrylate rods into the canal and beads around the infection site. At rod removal reaming and lavage were repeated. Antibiotic treatment was initiated with intravenous cephalothin, followed by prolonged oral treatment according to bacterial sensitivity. RESULTS: Cement rods and beads were removed 16 to 62 days after insertion. Intravenous antibiotics were continued for 6 weeks (3-13) and total antibiotic treatment length was 16 weeks (10-37). Total treatment time from presentation to full resolution averaged 8 months (2-18). One patient sustained a fracture requiring osteotomy and correction. At mean follow up of 41 months from rod removal (36-46), all patients are asymptomatic and fully functional with no clinical signs of infection. C-reactive protein is within normal limits in all 4 patients. CONCLUSIONS: The method presented combining reaming, lavage and local and systemic antibiotic treatment was found to be safe and effective in the treatment of CO, eradicating the infection and preventing further tissue loss. LEVEL OF EVIDENCE: Therapeutic study, clinical case series: level IV. PMID- 20574273 TI - Bone mineral density and functional measures in patients with arthrogryposis. AB - BACKGROUND: Patients with arthrogryposis often report decreased ambulation and physical activity. Given that skeletal mineralisation is responsive to force, we identified the need to characterize bone mineral density and functional measures in this population, and conducted a cross-sectional study to establish a reference for future investigations. METHODS: Thirty consecutive patients aged 5 to 18 years with either the diagnosis of amyoplasia or nonsyndromic arthrogryposis with predominantly lower extremity involvement underwent bone densitometry testing, and lumbar spine Z-scores were calculated against an age and sex-matched control population as is customary in children. Pediatric outcomes data collection instrument (PODCI) and functional independence measure for Children (WeeFIM) assessment forms were completed. Mean Z-scores, PODCI, and WeeFIM scores were calculated. Statistical analysis was performed to compare lumbar spine Z-scores between patients divided by ambulatory status and to correlate WeeFIM and PODCI scores. RESULTS: Mean lumbar spine Z-score was -0.47, with 73% of Z-scores being <0. Mean Z-score among nonambulators or home ambulators was -1.05, as compared to a mean Z-score among limited and unlimited community ambulators of -0.14 with a trend toward significance (P=0.10), and a dose-response relationship between higher bone density and increasing ambulatory function. Mean WeeFIM self-care and mobility quotient scores were 67.5/100 and 70.9/100, respectively. PODCI normative scores were decreased for upper extremity (10/50), transfer/basic mobility (-17/50), and sports/physical function (4/50), but normal in pain/comfort (45/50) and happiness (49/50). A linear relationship was noted between functional ambulation level and WeeFIM quotient and PODCI normative scores. There was good correlation between WeeFIM mobility and PODCI transfers and basic mobility standardised scores (R=0.86). CONCLUSIONS: This is the first study to measure bone mineral density in children with arthrogryposis, and shows it to be lower than age-matched means, especially in patients with limited ambulation. Objective measures of functional ability (WeeFIM and PODCI) are decreased and demonstrate a linear relationship with ambulatory level. Further investigation is needed to quantify long-term effects of entering adulthood with below average bone mineral density in patients with arthrogryposis. LEVEL OF EVIDENCE: Level II. PMID- 20574275 TI - Locking plate fixation for paediatric femur fractures. PMID- 20574277 TI - Abstracts of the 6th Congress of the European Association of Dermatologic Oncology. June 16-19, 2010. Athens, Greece. PMID- 20574276 TI - Re: a method for precise determination of the length of a segment of the spine, fused, or unfused. PMID- 20574403 TI - Management of infections caused by vancomycin-resistant gram-positive bacteria. PMID- 20574404 TI - Cytomegalovirus and transmission via breast milk: how to support breast milk to premature infants and prevent severe infection? PMID- 20574405 TI - Chemotherapy and surgery in children with cystic echinococcosis. PMID- 20574406 TI - Update on meningococcal disease mortality in the United States since 2002. PMID- 20574407 TI - Prevalence of scabies and head lice among students of secondary boarding schools in Kuching, Sarawak, Malaysia. PMID- 20574408 TI - Lack of sensitivity of QuantiFERON-TB gold test in tube in a child with tuberculous meningitis. PMID- 20574409 TI - Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases. AB - Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid hormone, secreted from the enteroendocrine K cells, which has insulin-releasing and extra pancreatic actions. GIP and its receptor present a widespread distribution in the mammalian brain where they have been implicated with synaptic plasticity, neurogenesis, neuroprotection and behavioral alterations. This review attempts to provide a comprehensive picture of the role of GIP in the central nervous system and to highlight recent findings from our group showing its potential involvement in neurological illnesses including epilepsies, Parkinson's disease and Alzheimer's disease. PMID- 20574410 TI - Performance of abdominal ultrasound for diagnosis of tuberculosis in HIV-infected persons living in Cambodia. AB - BACKGROUND: In resource-limited settings, abdominal ultrasound is often used to assist the diagnosis of tuberculosis (TB) in people with HIV (PLHIV), although data on performance characteristics are missing. METHODS: Cross-sectional study of PLHIV in Cambodia receiving a standardized TB diagnostic evaluation, including history, physical examination, chest radiography, microscopy and culture of various specimens, and abdominal ultrasound. Patients with at least one specimen culture positive for Mycobacterium tuberculosis were classified as having TB. RESULTS: TB was diagnosed in 37 (18%) of 212 PLHIV. Abdominal ultrasound was abnormal in 15 of 37 (41%) patients with TB compared with 14 of 175 (8%) without TB (P < 0.01). Predictors of TB disease included multiple enlarged (1.2 cm or greater) abdominal lymph nodes on ultrasound (adjusted odds ratio [OR], 6.4; 95% confidence interval [CI], 1.8-22.4), abnormal chest radiography (OR, 6.8; CI, 2.7 17.0), anorexia (OR, 4.6; CI, 1.8-11.7), and CD4 less than 200 cells/mm (OR, 3.3; CI, 1.2-9.1). Having multiple enlarged abdominal lymph nodes on ultrasound was 97.1% (CI, 93.5%-99.1%) specific for TB with a positive likelihood ratio of 11.4 (CI, 4.3-30.3). CONCLUSIONS: Abdominal ultrasound is a useful diagnostic test for TB disease in PLHIV, increasing the posttest probability of TB when multiple enlarged abdominal lymph nodes are visualized. Its wider use may accelerate access to TB treatment, potentially reducing mortality in PLHIV. PMID- 20574411 TI - Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. Hydroxyethyl cellulose-based universal placebo gel. AB - Dapivirine, a nonnucleoside reverse transcriptase inhibitor, is in development as a microbicide for the protection of women against HIV infection. A randomized, double-blind, phase 1 trial was conducted in 36 healthy HIV-negative women to compare the pharmacokinetics of 2 dapivirine vaginal gel formulations (0.05% each) and their safety with the hydroxyethyl cellulose-based universal placebo gel. Gel was self-administered once daily for a total of 11 days. Blood and vaginal fluid samples were collected sequentially over 24 days for pharmacokinetic analysis. Safety was evaluated by pelvic examination, colposcopy, adverse events, and clinical laboratory assessments. Adverse event profiles were similar for the 3 gels. Most events were mild and not related to study gel. Headache and vaginal hemorrhage (any vaginal bleeding) were most common. Plasma concentrations of dapivirine did not exceed 1.1 ng/mL. Steady-state conditions were reached within approximately 10 days. Dapivirine concentrations in vaginal fluids were slightly higher for Gel 4789, but Cmax values on days 1 and 14 were not significantly different. Terminal half-life was 72-73 hours in plasma and 15 17 hours in vaginal fluids. Both formulations of dapivirine gel were safe and well tolerated. Dapivirine was delivered to the lower genital tract at concentrations at least 5 logs greater than in vitro inhibitory concentrations. PMID- 20574413 TI - Comparative effect of interval and continuous training programs on serum uric acid in management of hypertension: a randomized controlled trial. AB - The purpose of the study was to investigate the effect of interval and continuous training program on blood pressure and serum uric acid (SUA) levels in subjects with hypertension. Three hundred and fifty-seven male patients with mild to moderate systolic blood pressure (SBP) between 140 and 179 and diastolic blood pressure (DBP) between 90 and 109 mm Hg essential hypertension were age-matched and grouped into interval, continuous, and control groups. The interval (work:rest ratio of 1:1) and continuous groups were involved in an 8-week interval and continuous training program of 45-60 minutes, at intensities of 60 79% of heart rate maximum, whereas the control group remained sedentary during this period. SBP, DBP, maximum oxygen uptake (VO2max) and SUA concentration were assessed. One-way analysis of variance and Scheffe and Pearson correlation tests were used in data analysis. Findings of the study revealed significant effect of exercise training program on VO2max, SBP, DBP, and SUA. However, there was no significant difference between the interval and continuous groups. Changes in VO2max negatively correlated with changes in SUA (r = -0.220) at p < 0.05. It was concluded that both moderate-intensity interval and continuous training programs are effective and neither seems superior to the other in the nonpharmacological management of hypertension and may prevent cardiovascular events through the downregulation of SUA in hypertension. Findings of the study support the recommendations of moderate-intensity interval and continuous training programs as adjuncts for nonpharmacological management of essential hypertension. PMID- 20574414 TI - ERPs reveal sensitivity to hypothetical contexts in spoken discourse. AB - We used event-related potentials to examine the interaction between two dimensions of discourse comprehension: (i) referential dependencies across sentences (e.g. between the pronoun 'it' and its antecedent 'a novel' in: 'John is reading a novel. It ends quite abruptly'), and (ii) the distinction between reference to events/situations and entities/individuals in the real/actual world versus in hypothetical possible worlds. Cross-sentential referential dependencies are disrupted when the antecedent for a pronoun is embedded in a sentence introducing hypothetical entities (e.g. 'John is considering writing a novel. It ends quite abruptly'). An earlier event-related potential reading study showed such disruptions yielded a P600-like frontal positivity. Here we replicate this effect using auditorily presented sentences and discuss the implications for our understanding of discourse-level language processing. PMID- 20574415 TI - Lessons for pharmacogenomics studies: association study between CYP2D6 genotype and tamoxifen response. AB - We earlier reported a significant association between the cytochrome P450 2D6 (CYP2D6) genotype and the clinical outcome in 282 Japanese breast cancer patients receiving tamoxifen monotherapy. Although many research groups have provided evidence indicating the CYP2D6 genotype as one of the strongest predictors of tamoxifen response, the results still remain controversial. We hypothesized that concomitant treatment was one of the causes of these controversial results. We then studied 167 breast cancer patients who received tamoxifen-combined therapy to evaluate the effects of concomitant treatment on the association analysis and observed no significant association between CYP2D6 genotype and recurrence-free survival (P=0.44, hazard ratio: 0.64, 95% confidential interval: 0.20-1.99 in patients with two variant alleles vs. patients without a variant allele). When we carried out two subgroup analyses for nodal status and tumor size, we observed a positive association between the CYP2D6 genotype and the clinical outcome only in patients who received tamoxifen monotherapy. This study explained a part of the discrepancies among the reported results. PMID- 20574412 TI - Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old. AB - BACKGROUND: Quadrivalent human papillomavirus vaccine (QHPV) is > 95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children. METHODS: HIV infected children (N = 126)-age > 7 to < 12 years, with a CD4% >= 15-and on stable antiretroviral therapy if CD4% was < 25-were blindly assigned to receive a dose of QHPV or placebo (3:1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose. RESULTS: The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in > 96% of QHPV recipients and in no placebo recipients. Geometric mean titer was > 27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls. CONCLUSIONS: QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted. PMID- 20574416 TI - Safety testing of indocyanine green with different surgical light sources and the protective effect of optical filters. AB - PURPOSE: The purpose of this study was to assess the light-induced cytotoxicity of indocyanine green (ICG) using different light sources commonly used in macular surgery and to assess the effect of optical filters. METHODS: Primary cultures of porcine retinal pigment epithelium cells were incubated with 0.5 mg/mL ICG solution dissolved in 5% glucose and illuminated with a surgical light fiber for 3 or 15 minutes. Halogen, mercury vapor, xenon, and metal halide light sources were used. Cell viability was assessed using the MTT assay. Retinal pigment epithelium cells without illumination served as controls. The decomposition of ICG after illumination was analyzed by high-performance liquid chromatography. RESULTS: Illumination of retinal pigment epithelium cells with all light sources with or without previous incubation with ICG did not affect cell viability compared with controls. Cell viability was significantly reduced when the cells were not rinsed immediately after incubation. The cytotoxic effect was abolished by a 475-nm long-pass filter. The high-performance liquid chromatography analysis of the illuminated ICG solution identified six cytotoxic ICG decomposition products. CONCLUSION: Optical filters that narrow the emission spectrum of the light sources reduce the light-induced cytotoxicity of ICG. Optical filters applied in ICG-assisted macular surgery may reduce the risk of intraoperative cell damage. PMID- 20574417 TI - MicroRNAs: small RNAs with big effects. AB - MicroRNAs (miRNAs) are evolutionarily conserved, small ( approximately 20-25 nucleotides), single-stranded molecules that suppress the expression of protein coding genes by translational repression, messenger RNA degradation, or both. More than 700 miRNAs have been identified in the human genome. Amazingly, a single miRNA can regulate the expression of hundreds of mRNAs or proteins within a cell. The small RNAs are fast emerging as master regulators of innate and adaptive immunity and likely to play a pivotal role in transplantation. The clinical application of RNA sequencing ("next-generation sequencing") should facilitate transcriptome profiling at an unprecedented resolution. We provide an overview of miRNA biology and their hypothesized roles in transplantation. PMID- 20574418 TI - Neurologic problems after pediatric liver transplantation and combined liver and bowel transplantations: a single tertiary centre experience. AB - BACKGROUND: Neurologic problems postpediatric liver transplant have been reported in up to 46% of cases, and mortality is higher in the pediatric age group compared with adults. METHODS: An internal audit was performed in all children undergoing solid organ transplant in the Liver unit at Birmingham Children's Hospital to identify children with neurologic complications. RESULTS: One hundred seventeen children underwent 127 pediatric liver transplant and combined liver and small bowel transplant episodes over a 4-year period. Neurologic problems were present after 31 of 127 (24.4%) transplant episodes involving 29 children. Seizures were the most common presentation (n=17; 54.8%), followed by encephalopathy (n=11; 35.4%) and posterior reversible leukoencephalopathy syndrome (n=6; 19.3%). Other complications noted were central nervous system infection (n=4; 12.9%), cerebrovascular accident (n=3; 9.6%), peripheral neuropathy (n=2; 6.4%) and tremor, transient blurring of vision, auditory hallucinations and choreoathetosis (n=1; 3.2%) each. There were 27 deaths (23%) in 117 children after transplantation, and the mortality rate in the group with neurologic problem was 13.3% (n=4) compared with 26.7% (n=23) in children without neurologic problem (odds ratio 0.45, 95% confidence interval 0.142-1.439). In contrast to other studies, our study showed that the mortality rate was not higher in children with neurologic problems. CONCLUSION: Neurologic problems were relatively common after pediatric liver transplantation and combined liver and bowel transplantations; however, the mortality was lower when compared with previously reported studies. PMID- 20574419 TI - A systematic review on steroid withdrawal between 3 and 6 months after kidney transplantation. AB - BACKGROUND: Steroid withdrawal (SW) after the first posttransplant months in patients receiving a kidney transplant has been recently discouraged in clinical guidelines. METHODS: A systematic review and meta-analysis of randomized controlled trials assessing SW (beyond the second week after kidney transplantation) was performed. Only trials using a calcineurin inhibitor plus mycophenolic acid were included. RESULTS: The nine trials (1820 participants) randomly withdrew steroids between 3 and 6 months after transplantation. Death and graft loss were similar in SW and control patients. Including all trials, acute rejection was not more frequent after SW, but stratifying by the drug used, cyclosporine A (CsA) was associated with an increased incidence of overall acute rejection (risk ratio 1.42, 95% confidence interval 1.08-1.87) or biopsy-proven acute rejection (risk ratio 1.61 95% confidence interval 1.20-2.17). Contrarily, tacrolimus allowed SW without increased biopsy-proven acute rejection (P interaction=0.005). Serum cholesterol level was lower after SW than in controls using CsA or tacrolimus. Serum creatinine, blood pressure, serum triglycerides, new-onset diabetes mellitus, infections, or malignancies were similar in SW and control patients. CONCLUSIONS: SW after 3 to 6 months of kidney transplantation is associated with increased rates of acute rejection only if CsA is used but not with tacrolimus. Graft function and survival remain stable up to 3 years after transplantation, the longest follow-up reported. The interest for late SW has decreased during the past years in the literature. More trials with carefully designed outcome measures are needed in patients treated with low-exposure tacrolimus and mycophenolic acid derivatives. PMID- 20574420 TI - Structure of the gating ring from the human large-conductance Ca(2+)-gated K(+) channel. AB - Large-conductance Ca(2+)-gated K(+) (BK) channels are essential for many biological processes such as smooth muscle contraction and neurotransmitter release. This group of channels can be activated synergistically by both voltage and intracellular Ca(2+), with the large carboxy-terminal intracellular portion being responsible for Ca(2+) sensing. Here we present the crystal structure of the entire cytoplasmic region of the human BK channel in a Ca(2+)-free state. The structure reveals four intracellular subunits, each comprising two tandem RCK domains, assembled into a gating ring similar to that seen in the MthK channel and probably representing its physiological assembly. Three Ca(2+) binding sites including the Ca(2+) bowl are mapped onto the structure based on mutagenesis data. The Ca(2+) bowl, located within the second RCK domain, forms an EF-hand like motif and is strategically positioned close to the assembly interface between two subunits. The other two Ca(2+) (or Mg(2+)) binding sites, Asp 367 and Glu 374/Glu 399, are located on the first RCK domain. The Asp 367 site has high Ca(2+) sensitivity and is positioned in the groove between the amino- and carboxy terminal subdomains of RCK1, whereas the low-affinity Mg(2+)-binding Glu 374/Glu 399 site is positioned on the upper plateau of the gating ring and close to the membrane. Our structure also contains the linker connecting the transmembrane and intracellular domains, allowing us to dock a voltage-gated K(+) channel pore of known structure onto the gating ring with reasonable accuracy and generate a structural model for the full BK channel. PMID- 20574421 TI - Loss of fish actinotrichia proteins and the fin-to-limb transition. AB - The early development of teleost paired fins is strikingly similar to that of tetrapod limb buds and is controlled by similar mechanisms. One early morphological divergence between pectoral fins and limbs is in the fate of the apical ectodermal ridge (AER), the distal epidermis that rims the bud. Whereas the AER of tetrapods regresses after specification of the skeletal progenitors, the AER of teleost fishes forms a fold that elongates. Formation of the fin fold is accompanied by the synthesis of two rows of rigid, unmineralized fibrils called actinotrichia, which keep the fold straight and guide the migration of mesenchymal cells within the fold. The actinotrichia are made of elastoidin, the components of which, apart from collagen, are unknown. Here we show that two zebrafish proteins, which we name actinodin 1 and 2 (And1 and And2), are essential structural components of elastoidin. The presence of actinodin sequences in several teleost fishes and in the elephant shark (Callorhinchus milii, which occupies a basal phylogenetic position), but not in tetrapods, suggests that these genes have been lost during tetrapod species evolution. Double gene knockdown of and1 and and2 in zebrafish embryos results in the absence of actinotrichia and impaired fin folds. Gene expression profiles in embryos lacking and1 and and2 function are consistent with pectoral fin truncation and may offer a potential explanation for the polydactyly observed in early tetrapod fossils. We propose that the loss of both actinodins and actinotrichia during evolution may have led to the loss of lepidotrichia and may have contributed to the fin-to-limb transition. PMID- 20574422 TI - Blindsight depends on the lateral geniculate nucleus. AB - Injury to the primary visual cortex (V1) leads to the loss of visual experience. Nonetheless, careful testing shows that certain visually guided behaviours can persist even in the absence of visual awareness. The neural circuits supporting this phenomenon, which is often termed blindsight, remain uncertain. Here we demonstrate that the thalamic lateral geniculate nucleus (LGN) has a causal role in V1-independent processing of visual information. By comparing functional magnetic resonance imaging (fMRI) and behavioural measures with and without temporary LGN inactivation, we assessed the contribution of the LGN to visual functions of macaque monkeys (Macaca mulatta) with chronic V1 lesions. Before LGN inactivation, high-contrast stimuli presented to the lesion-affected visual field (scotoma) produced significant V1-independent fMRI activation in the extrastriate cortical areas V2, V3, V4, V5/middle temporal (MT), fundus of the superior temporal sulcus (FST) and lateral intraparietal area (LIP) and the animals correctly located the stimuli in a detection task. However, following reversible inactivation of the LGN in the V1-lesioned hemisphere, fMRI responses and behavioural detection were abolished. These results demonstrate that direct LGN projections to the extrastriate cortex have a critical functional contribution to blindsight. They suggest a viable pathway to mediate fast detection during normal vision. PMID- 20574423 TI - Effects of long-term treatment for obstructive sleep apnea on pulse wave velocity. AB - Continuous positive airway pressure (CPAP) treatment improves endothelial function and sympathetic activity in patients with obstructive sleep apnea (OSA). However, the long-term effects of CPAP on pulse wave velocity (PWV), which reflects arterial stiffness that is associated with cardiovascular events, have not been evaluated in OSA patients with or without hypertension (HT). In this study, 212 male OSA patients who had been receiving CPAP treatment for 2 years and were divided into two groups, those with HT (n=114) and those without (n=98), were studied. In both HT and normotensive (NT) patients, PWV decreased significantly over the first 6 months of treatment (P=0.005 and 0.010, respectively), before increasing gradually from 6 to 24 months. Body mass index (BMI), body weight, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels decreased significantly in the HT group over the 2 years of CPAP treatment (P<0.001 for all). In contrast, only HR decreased significantly in the NT group over the 2 years of treatment (P<0.001). Multivariate regression analysis revealed that age (P=0.008), decreases in DBP (P<0.001) and HR (P<0.001) and higher initial levels of serum high-density lipoprotein-cholesterol (P=0.040) were independent factors related to changes in PWV over the 2 years of CPAP treatment in all patients. In conclusion, we found a significant decrease in PWV in both NT and HT patients after 6 months of CPAP treatment. In HT patients, long-term CPAP treatment significantly decreases blood pressure, which may contribute to explain the PWV improvement. PMID- 20574424 TI - Early physical activity promotes lower prevalence of chronic diseases in adulthood. AB - Epidemiological studies have shown high rates of occurrence of arterial hypertension and type 2 diabetes mellitus among adults, and early preventive actions are extremely relevant for public policy strategies. The purpose of this study was to analyze the relationship between the prevalence of arterial hypertension and type 2 diabetes in adulthood and physical activity (currently and in childhood/adolescence). A retrospective study was carried out from March to November of 2009. Data were collected through interviews, and both diseases were assessed through self-report and confirmed by previous medical diagnosis. Current physical activity and that performed in childhood (7-10 years old) and adolescence (11-17 years old) were analyzed. Of the 1436 adults analyzed in this survey, approximately 61% were women (n=881). Respondents' ages ranged from 18 to 94.8 years, and 20.2% of the total participants were >/=65 years old. Our results show that men (18%) were more physically active than women (9.4%), whereas younger respondents and those with more formal education exhibited greater physical activity levels (P<0.001). Obese subjects presented lower physical activity levels (P=0.027). Physical activity in youth was associated with lower rates of occurrence of arterial hypertension (odds ratio (OR)=0.42 (95% confidence interval (CI)=0.29-0.62)) and type 2 diabetes mellitus (OR=0.29 (95% CI=0.15-0.56)) in adulthood, but current physical activity was not related to these outcomes. Our study reveals a positive relationship between early physical activity in both childhood and adolescence and lower rates of occurrence of endocrine and cardiovascular diseases in adulthood. PMID- 20574425 TI - Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype. AB - Chromosomal translocations and inversions are present in ~0.6-1% of individuals. Although the majority are inherited, and the familial transmission across generations is well reported, reports of homozygosity are relatively rare, with most data in the form of individual case reports. A systematic review of all published cases was performed with particular attention to origin, ascertainment and phenotype of the reported homozygosity. A total of 10 cases of Robertsonian translocation (RBT), 6 reciprocal translocation and 19 cases of inversion homozygosity were identified. In RBT homozygosity, the majority of individuals are phenotypically normal, arise from inbreeding within a family that carries a familial translocation, and are ascertained following identification of an existing familial rearrangement rather than any feature specific to the homozygosity. In addition, they are fertile and as expected, their offspring are heterozygous for the translocation. For reciprocal translocations, homozygosity arises in individuals born to related parents from a family who harbor a unique familial translocation. Ascertainment is following investigation of phenotypic abnormalities resulting from consanguinity per se and/or the unmasking of a specific gene mutation. For chromosomal inversions, homozygosity may originate from either related or non-consanguinous parentage. Although many cases are ascertained because of an associated phenotypic abnormality, a high proportion of cases are of normal phenotype and a direct causal relationship is uncertain. There are fewer reports of both Robertsonian and inversion homozygosity than may be expected from the relative frequencies of each class within the population. PMID- 20574426 TI - The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population. AB - It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in Japanese subjects by analyzing 488 cases and 398 controls. A meta-analysis was performed involving two previous association studies. We also analyzed the association between the single nucleotide polymorphism and clinical parameters in the general Japanese population (n=1854). In the case-control study, the A allele of GCKR rs780094 was associated with a reduced risk of T2DM (odds ratio=0.711 (95% confidence interval=0.589-0.859), P=4.2 * 10(-4)). A meta-analysis confirmed the association of GCKR rs780094 with T2DM susceptibility. In the general Japanese population, subjects with the A/A genotype had lower levels of FPG, fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the G/G genotype. Conversely, subjects with the A/A genotype had higher levels of TG than those with the G/G genotype. We replicated GCKR rs780094 as a marker of T2DM susceptibility in Japanese subjects. This suggests that GCKR rs780094 is a common variant for T2DM susceptibility in various ethnic groups. PMID- 20574427 TI - Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup I. AB - We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted. PMID- 20574428 TI - Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations. AB - Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) and transmitted as an autosomal recessive trait. This is the first systematic mutation screen in Chinese MPS IVA patients. Mutation detections in 24 unrelated Chinese MPS IVA patients were performed by PCR and direct sequencing of exons or the mRNA of GALNS. A total of 42 mutant alleles were identified, belonging to 27 different mutations. Out of the 27 mutations, 16 were novel, including 2 splicing mutations (c.567-1G>T and c.634-1G>A), 2 nonsense mutations (p.W325X and p.Q422X) and 12 missense mutations (p.T88I, p.H142R, p.P163H, p.G168L, p.H236D, p.N289S, p.T312A, p.G316V, p.A324E, p.L366P, p.Q422K and p.F452L). p.G340D was found to be a common mutation in the Chinese MPS IVA patients, accounting for 16.7% of the total number of mutant alleles. The results show that the mutations in Chinese MPS IVA patients are also family specific but have a different mutation spectrum as compared to those of other populations. PMID- 20574429 TI - Tetraploid cancer cell precursors. PMID- 20574430 TI - Testosterone and chronic sildenafil/tadalafil anti-apoptotic role in aged diabetic rats. AB - This work aimed to assess the cavernous anti-apoptotic role of using chronic low dose sildenafil/tadalafil with and without testosterone (T) in aged diabetic rats. In all, 140 Sprague-Dawley aged rats were divided into the following groups: controls; induced diabetic rats; diabetic rats that received intramuscular depot T once every 4 weeks; diabetic rats on sildenafil 2 mg kg(-1) orally daily; diabetic rats on T and daily sildenafil; diabetic rats on tadalafil 0.45 mg kg(-1) orally every other day; diabetic rats on every-other-day tadalafil and T; diabetic rats on alternate sildenafil and tadalafil; and diabetic rats on alternate sildenafil, tadalafil and T. After 12 weeks, Bax (apoptotic factor), Bcl(2) (B-cell lymphoma 2; anti-apoptotic factor), cGMP (cyclic guanosine monophosphate) were estimated in their cavernous tissues. Compared with the controls, aged diabetic rats showed significant increased cavernous tissue Bax and significant decreased Bcl(2), in which diabetic rats injected with T showed the reverse compared with the diabetic rats. Diabetic rats on sildenafil or tadalafil showed significant increased cavernous Bcl(2) and decreased Bax with upgraded Bcl(2)/Bax ratio that was improved being on T. Diabetic rats on alternate sildenafil/tadalafil with or without T showed further significant increased cavernous tissue Bcl(2) with upgraded Bcl(2)/Bax ratio. It is concluded that frequent low-dose use of sildenafil and/or tadalafil combined with T would be predicted to have a pronounced anti-apoptotic cavernous tissue effect on the cavernous tissues of aged diabetic rats. PMID- 20574431 TI - Insight on pathogenesis of lifelong premature ejaculation: inverse relationship between lifelong premature ejaculation and obesity. AB - Although both biological and psychological factors are important in the etiology, the exact pathogenesis of lifelong premature ejaculation (PE) remains to be clarified. Obesity is a worldwide epidemic that contributes to many chronic diseases. Obesity is associated with erectile dysfunction, but the relationship between obesity and PE has not yet been specifically investigated. The aim of this study was to evaluate the relationships of these two conditions. Between January 2008 and December 2009, we evaluated consecutive patients with lifelong PE in the urology outpatient clinic. Control cases without lifelong PE were selected randomly among cases attending the department of internal medicine for a checkup procedure. The age and sex of control group were matched with that of the study group. Body mass index (BMI) of each case was calculated using the World Health Organization criteria by the measurements of the physician instead of relying on verbal expressions. The mean (+/-s.d.) age of the premature ejaculators was 31.7+/-5.7 (range 21-51) years and in the control cases it was 32.3+/-6.7 (range 22-54) years. The comparison of the mean (+/-s.d.) weight between the study (74.1+/-11.2 kg) and control groups (81.9+/-6.4 kg) revealed a significant difference (P<0.001). The mean BMI of premature ejaculators (24.9+/ 3.4 kg m(-2)) was lower than the mean BMI of control (27.5+/-3.6 kg m(-2); P<0.001). As the BMI increased, the number of patients decreased in the PE group. The number of the obese cases in the control group (n=26, 24.1%) was three times greater than the obese premature ejaculators (P<0.005), and the number of PE patients were approximately two times greater than the control cases in the normal-weight class (P<0.001). This is the first prospective study that investigated the relationship between lifelong PE and obesity, and we found that patients with lifelong PE were leaner than the healthy control cases. PMID- 20574432 TI - Sexual functions and quality of life in women with tubal sterilization. AB - The aim of this study was to evaluate the sexual functions and quality of life of women who have undergone tubal sterilization after tubal surgery. In all, 90 active premenopausal women, who had undergone tubal sterilization at least 1 year ago and been admitted to four different hospitals, were included in the study group. A total of 100 women at a similar age range, admitted to the same four hospitals for routine health controls, were included in the control group. To obtain sexual function assessments, the patients were asked to fill out Female Sexual Function Index (FSFI) questionnaire. The participants were also asked to fill out Medical Outcomes Study Short Form (SF-36) questionnaire. All values were found to be lower in the tubal sterilization (TS) group and the differences between groups were statistically significant in domain except for pain and lubrication. Similarly, in the analysis of SF-36 scores, there were differences in comparison with the TS group in all domains. In the evaluation of the relationship of FSFI with educational level in the TS group, it was found that, while the educational level increased, all domain scores also increased, and this increase was statistically significant in all domains except pain. The termination of fertility, which is one of the important abilities of women, with tubal sterilization, may be a risk factor for female sexual dysfunction in people with low educational levels. PMID- 20574433 TI - Outcomes of lateral retroperitoneal reservoir placement of three-piece penile prosthesis in patients following radical prostatectomy. AB - While placement of a three-piece inflatable penile prosthesis (IPP) with a midline reservoir can be performed with favorable outcomes after radical prostatectomy (RP), postoperative fascial scarring can introduce surgical complexity, increase intra-operative complications and/or potential obstacles for future inguinal and/or perineal surgeries. We describe the implantation of the IPP with lateral reservoir placement through a separate incision to avoid surgical complications. We obtained clinical characteristics of all patients (1998-2009) who underwent RP before IPP placement with lateral reservoir placement (cases). For comparison, patients who underwent IPP placement with midline reservoir placement were also identified (controls). Thirty-one patients with a history of RP underwent IPP placement using the lateral placement technique without intra-operative or post-operative complications. There were no significant differences in the intra-operative complication rate among 31 control patients. However, at a median follow-up of >2 years, there was a significantly higher rate of post-operative complications in controls, likely reflecting the increased co-morbidities in this group. The results of this study suggest that three-piece IPP with lateral retroperitoneal reservoir implantation is associated with comparable long-term outcomes and can be performed safely in patients who have previously undergone RP. PMID- 20574434 TI - Gene regulation by 1,25-dihydroxyvitamin D3 in CD4+CD25+ cells is enabled by IL 2. AB - Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) enhances the immunoregulatory ability of CD4+CD25+ T cells residing in the skin-draining lymph nodes (SDLNs) of mice. The mechanisms responsible were investigated by examining the expression of 84 cytokine and cytokine-related genes in a 96-well gene array. CD4+CD25+ cells isolated from the SDLNs of BALB/c mice, 24 and 96 hours after topical treatment with 1,25(OH)(2)D(3), consistently expressed increased IL-2 mRNA levels and also secreted enhanced quantities of IL-2 after ex vivo stimulation with phorbol 12 myristate 13-acetate and ionomycin. CD4+CD25+ cells from the lymph nodes of naive mice constitutively express the vitamin D receptor, allowing direct modulation by 1,25(OH)(2)D(3). However, in vitro treatment with 1,25(OH)(2)D(3) did not modify the expression of 84 tested cytokine and cytokine-related mRNAs. It was only in the presence of IL-2 that 1,25(OH)(2)D(3) increased the expression of genes including IL-2 and TLR4. Further, 1,25(OH)(2)D(3) enhanced the ability of IL-2 to stimulate CD4+CD25+ cells to proliferate in vitro and also regulate contact hypersensitivity responses on adoptive transfer into naive mice. Therefore, 1,25(OH)(2)D(3) enabled by IL-2 can directly enhance the regulatory potential of CD4+CD25+ T cells to control immune disease. PMID- 20574435 TI - CD44-deficient mice do not exhibit impairment of epidermal Langerhans cell migration to lymph nodes after epicutaneous sensitization with protein. PMID- 20574436 TI - Squamous cell carcinoma of the skin shows a distinct microRNA profile modulated by UV radiation. PMID- 20574437 TI - Mutations in sterol O-acyltransferase 1 (Soat1) result in hair interior defects in AKR/J mice. PMID- 20574438 TI - Changes in the ceramide profile of atopic dermatitis patients. PMID- 20574439 TI - XPA gene mutations resulting in subtle truncation of protein in xeroderma pigmentosum group A patients with mild skin symptoms. AB - Comparisons of the clinical manifestations with gene mutations in patients with xeroderma pigmentosum group A (XPA) have suggested that those with mutations closer to the C-terminal coding region of the XPA gene have milder neurological and cutaneous symptoms. Here we report on four middle-aged, newly diagnosed Japanese XPA patients whose unusually mild symptoms, especially those affecting the skin, implicate a reduced association of a subtle defect in the C-terminus of XPA protein with skin lesions. All patients had a heterozygous G -> C transversion at the splice acceptor site of XPA intron 3. We identified previously unreported heterozygous mutations in exon 6: a single-base insertion (690insT) in one patient and a four-base insertion (779insTT and 780insTT) in the other patients. These mutations led to the frameshift that created new premature termination codons, resulting in the production of truncated XPA proteins. They were longer than any previously reported truncated XPA protein, suggesting that the minimal cutaneous symptoms in these patients are due to a higher residual level of XPA protein activity and that the subtle defect in the C-terminus of XPA protein is more closely related to neurological impairment than to cutaneous abnormalities. PMID- 20574440 TI - The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid photosensitizes the formation of oxidized guanines in cellulo after UV-A or UV-B exposure. AB - The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) is water soluble and is widely used in the cosmetic industry because it absorbs strongly at UV-B wavelengths. Previous studies have shown that PBSA, photoexcited by UV-B, oxidizes guanine bases in vitro. Because of its potential phototoxic effect, it is important to determine whether PBSA photosensitizes in cellulo the formation of oxidatively generated DNA damage on UV exposure. For this purpose, we investigated, in vitro and in cellulo, the effect of PBSA on DNA bases after UV-A or UV-B irradiation. To monitor the formation of oxidized bases and cyclobutane pyrimidine dimers (CPDs), DNA was digested either with FaPy-DNA glycosylase and endonuclease III or with T4 endonuclease V and photolyase, then analyzed by means of neutral- and glyoxal-agarose gel electrophoresis and ligation-mediated PCR. In cellulo, we found that PBSA provided good protection against CPD formation after UV-B exposure. However, PBSA also photosensitized oxidized guanines on UV-A and UV-B irradiation. Our results indicate that PBSA has the potential to function as a double-edged sword toward DNA and question its suitability for sunscreen applications. PMID- 20574441 TI - The wrath of RAFs: rogue behavior of B-RAF kinase inhibitors. PMID- 20574442 TI - Vaccination with TAT-antigen fusion protein induces protective, CD8(+) T cell mediated immunity against Leishmania major. AB - In murine leishmaniasis, healing is mediated by IFN-gamma-producing CD4(+) and CD8(+) T cells. Thus, an efficacious vaccine should induce Th1 and Tc1 cells. Dendritic cells (DCs) pulsed with exogenous proteins primarily induce strong CD4 dependent immunity; induction of CD8 responses has proven to be difficult. We evaluated the immunogenicity of fusion proteins comprising the protein transduction domain of HIV-1 TAT and the Leishmania antigen LACK (Leishmania homolog of receptors for activated C kinase), as TAT-fusion proteins facilitate major histocompatibility complex class I-dependent antigen presentation. In vitro, TAT-LACK-pulsed DCs induced stronger proliferation of Leishmania-specific CD8(+) T cells compared with DCs incubated with LACK alone. Vaccination with TAT LACK-pulsed DCs or fusion proteins plus adjuvant in vivo significantly improved disease outcome in Leishmania major-infected mice and was superior to vaccination with DCs treated with LACK alone. Vaccination with DC+TAT-LACK resulted in stronger proliferation of CD8(+) T cells when compared with immunization with DC+LACK. Upon depletion of CD4(+) or CD8(+) T cells, TAT-LACK-mediated protection was lost. TAT-LACK-pulsed IL-12p40-deficient DCs did not promote protection in vivo. In summary, these data show that TAT-fusion proteins are superior in activating Leishmania-specific Tc1 cells when compared with antigen alone and suggest that IL-12-dependent preferential induction of antigen-specific CD8(+) cells promotes significant protection against this important human pathogen. PMID- 20574443 TI - Revertant mosaicism due to a second-site mutation in COL7A1 in a patient with recessive dystrophic epidermolysis bullosa. AB - Despite the high incidence of revertant mosaicism (35%) in patients with the genetic skin disease epidermolysis bullosa (EB) due to correcting mutations in the genes COL17A1 and LAMB3, revertant mosaicism has not been described for COL7A1 until recently. Mutations in COL7A1 are responsible for the most devastating form of EB in adults, which is characterized by cocooned "mitten" deformities of the hands. This report shows in vivo reversion of an inherited COL7A1 mutation in a patient with recessive dystrophic EB who was homozygous for the frameshift mutation COL7A1:c.6527insC,p.2176FsX337. The patient exhibited a patch of clinically healthy revertant skin on her left forearm. The second-site mutation c.6528delT, which is present in revertant keratinocytes, resulted in correction of the reading frame. As the new CCC codon codes for the same amino acid proline as the wild-type codon CCT, the revertant cells expressed wild-type type VII collagen polypeptide, leading to restoration of skin function. We hypothesize that, on careful examination, revertant mosaicism might be found to be more common in patients with type VII collagen-deficient EB. Furthermore, the revertant keratinocytes might offer the possibility to explore cell-based therapeutic strategies, by culturing in vitro and subsequently grafting as part of bioengineered dermo-epidermal substitutes on affected skin. PMID- 20574444 TI - De novo production of dermal papilla cells during the anagen phase of the hair cycle. PMID- 20574445 TI - A non-synonymous SNP within membrane metalloendopeptidase-like 1 (MMEL1) is associated with multiple sclerosis. AB - Several single-nucleotide polymorphism (SNP) genome-wide association studies (GWASs) have been completed in multiple sclerosis (MS). Follow-up studies of the variants with the most promising rankings, especially when supplemented by informed candidate gene selection, have proven to be extremely successful. In this study we report the results of a multi-stage replication analysis of the putatively associated SNPs identified in the Wellcome Trust Case Control Consortium non-synonymous SNP (nsSNP) screen. In total, the replication sample consisted of 3444 patients and 2595 controls. A combined analysis of the nsSNP screen and replication data provides evidence implicating a novel additional locus, rs3748816 in membrane metalloendopeptidase-like 1 (MMEL1; odds ratio=1.16, P=3.54 * 10-6) in MS susceptibility. PMID- 20574446 TI - Indication-specific 6-h systolic blood pressure thresholds can approximate 24-h determination of blood pressure control. AB - Ambulatory blood pressure monitoring (ABPM) is an accurate method for evaluating hypertension, yet its use in clinical practice may be limited by availability, cost and patient inconvenience. The objective of this study was to investigate the ability of a 6-h ABPM window to predict blood pressure control, judging by that of the full 24-h ABPM session across several clinical indications in a cohort of 486 patients referred for ABPM. Sensitivities and specificities of the 6-h systolic blood pressure mean to accurately classify patients as hypertensive were determined using a fixed reference point of 130 mm Hg for the 24-h mean. For four common indications, in which ABPM was ordered, prediction tables were constructed varying the thresholds for the 6-h mean to find the optimal value that best predicted the 24-h hypertensive status as determined from the full 24-h interval. Using a threshold of 137 mm Hg for the indications of borderline hypertension, evaluation of current antihypertensive regimen and suspected white coat hypertension, sensitivity and specificity ranged from 0.83-0.88 to 0.80 0.88, respectively, for the ability of 6-h ABPM to correctly categorize hypertensive status. Using 133 mm Hg as the threshold for treatment resistance resulted in a sensitivity and specificity of 0.93 and 0.83, respectively. We conclude that a shortened ABPM session of 6 h can be used to accurately classify blood pressure as controlled or not, based on the results of a 24-h session. The optimal 6-h threshold for comparison depends upon indication for referral. PMID- 20574447 TI - The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism. AB - Metabolic syndrome (MS) is frequent clinical condition in patients with hypertension. Primary aldosteronism (PA) is a common form of secondary hypertension. This study was aimed at investigating the prevalence of the MS and its components in the two major forms of PA, in unilateral aldosterone-producing adenoma (APA) and bilateral aldosterone overproduction because of idiopathic hyperaldosteronism (IHA). The diagnosis of the particular form of PA was based on adrenal venous sampling and/or successful surgery confirmed by histopathological examination. We analyzed clinical and laboratory data from 100 patients with PA (50 patients with IHA and 50 patients with APA) and from 90 patients with essential hypertension (EH). Metabolic profiles of patients with bilateral form of PA (because of IHA) were similar to EH, but differed from those in patients with unilateral form of PA (APA). The prevalence of the MS (62% in IHA, 34% in APA and 56% in EH), the body mass index value (30+/-4 kg m(-2) in IHA, 27+/-5 kg m(-2) in APA and 29+/-5 kg m(-2) in EH) and triglycerides levels (1.9+/-0.9 mmol l(-1) in IHA,1.4+/-0.8 mmol l(-1) in APA and 2.01+/-1.39 mmol l(-1) in EH) were all significantly (P<0.05) higher in IHA compared with APA patients. Metabolic profile of patients with bilateral form of PA (because of IHA) is similar to EH in contrast to unilateral form of PA (APA). PMID- 20574448 TI - Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. AB - Post-translational modification of histones provides an important regulatory platform for processes such as gene transcription and DNA damage repair. It has become increasingly apparent that the misregulation of histone modification, which is caused by the deregulation of factors that mediate the modification installation, removal and/or interpretation, actively contributes to human cancer. In this Review, we summarize recent advances in understanding the interpretation of certain histone methylations by plant homeodomain finger containing proteins, and how misreading, miswriting and mis-erasing of histone methylation marks can be associated with oncogenesis and progression. These observations provide us with a greater mechanistic understanding of epigenetic alterations in human cancers and might also help direct new therapeutic interventions in the future. PMID- 20574449 TI - Non-germline genetically engineered mouse models for translational cancer research. AB - Genetically engineered mouse models (GEMMs) of cancer have affected virtually all areas of cancer research. However, the accelerated discovery of new cancer genes emerging from large-scale cancer genomics and new chemical entities pouring from the drug discovery pipeline have strained the capacity of traditional germline mouse models to provide crucial insights. This Review introduces new approaches to modelling cancer, with emphasis on a growing collection of non-germline GEMMs (nGEMMs). These offer flexibility, speed and uniformity at reduced costs, thus paving the way for much needed throughput and practical preclinical therapeutic testing models. PMID- 20574451 TI - Breast and prostate cancer: familial associations. PMID- 20574450 TI - Targeting the tumour vasculature: insights from physiological angiogenesis. AB - The cardiovascular system ensures the delivery of nutrients, oxygen, and blood and immune cells to all organs and tissues: it is also responsible for the removal of waste metabolites. The vascular system develops and matures through two tightly regulated processes: vasculogenesis and angiogenesis. Angiogenesis is active only under specific physiological conditions in healthy adults but the vasculature can be aberrantly activated to generate new blood vessels during pathological conditions such as cancer and chronic inflammation. In this Opinion article we discuss the parallels and differences in the angiogenic process under either a physiological or a pathological state, especially tumorigenesis. PMID- 20574453 TI - Correction of B-cell development in Btk-deficient mice using lentiviral vectors with codon-optimized human BTK. AB - X-linked agammaglobulinemia (XLA) is the most common primary immunodeficiency (PID) in man and caused by mutations in the Bruton's tyrosine kinase (BTK) gene. XLA is characterized by a B-cell differentiation arrest in bone marrow, absence of mature B cells and immunoglobulins (Igs), and recurrent bacterial infections. We used self-inactivating lentiviral vectors expressing codon-optimized human BTK under the control of three different ubiquitous or B cell-specific promoters. Btk /- mice engrafted with transduced cells showed correction of both precursor B cell and peripheral B-cell development. Lentiviral vectors containing the wildtype BTK sequence did not correct the phenotype. All treated mice with codon optimized BTK exhibited the recovery of B1 cells in the peritoneal cavity, and of serum IgM and IgG3 levels. Calcium mobilization responses upon B-cell receptor stimulation as well as in vivo responses to T cell-independent antigens were restored. Viral promoters overexpressing BTK >100-fold above normal resulted in erythro-myeloid proliferations independent of insertional mutagenesis. However, transplantation into secondary Btk-/- recipients using cellular promoters resulted in functional restoration of peripheral B cells and IgM levels, without any adverse effects. In conclusion, transduction of human BTK corrects B-cell development and antigen-specific antibody responses in Btk-/- mice, thus indicating the feasibility of lentiviral gene therapy for XLA, provided that BTK expression does not vastly exceed normal levels. PMID- 20574452 TI - Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells. AB - The HOX genes encode a family of transcription factors that are dysregulated in several malignancies and have been implicated in oncogenesis and cancer cell survival. Disruption of HOX protein function using the peptide HXR9 has shown anti-tumor effects against melanoma, lung cancer and renal cancer. In this report, we evaluated the expression of all 39 HOX genes in a panel of six malignant B-cell lines, including multiple myeloma cells and found different levels of expression of HOX family members suggesting that they also have a role in malignant B-cell survival. We show that disrupting HOX function using the peptide HXR9 induces significant cytotoxicity in the entire panel of cell lines. Importantly, we found that the cytotoxic effects of HXR9 can be enhanced by combining it with ch128.1Av, an antibody-avidin fusion protein specific for the human transferrin receptor 1 (CD71). Iron starvation induced by the fusion protein contributes to the enhanced effect and involves, at least in part, the induction of a caspase-independent pathway. These results show the relevance of HOX proteins in malignant B-cell survival and suggest that our therapeutic strategy may be effective in the treatment of incurable B-cell malignancies such as multiple myeloma. PMID- 20574454 TI - Polymorphisms in the base excision repair pathway and graft-versus-host disease. AB - Graft-versus-host disease (GVHD) is a frequent complication after hematopoietic cell transplant (HCT). Tissue damage as a result of chemoradiation injury is the initiating event in the pathogenesis of acute GVHD. Variations in DNA repair can influence the amount of tissue damage in response to alkylating agents and ionizing radiation used as conditioning during HCT. As DNA damage caused by these agents is repaired by the base excision repair (BER) pathway, we hypothesized that single-nucleotide polymorphisms (SNPs) in BER pathway will be associated with GVHD after HCT. Hence, we analyzed 179 SNPs in BER pathway in 470 recipients of allogeneic HCT for association with acute and chronic GVHD. In multivariate analysis, one SNP (rs6844176) in RFC1 (replication factor C (activator 1)) gene was independently associated with a higher risk of grade II-IV acute GVHD (relative risk (RR): 1.39, 95% confidence interval (CI): 1.14-1.70, P=0.001), and showed a trend toward higher risk of grade III-IV acute GVHD (RR: 1.33, 95% CI: 0.95-1.85, P=0.09). One SNP in PARP1 gene (rs1805410) was associated with a higher risk of chronic GVHD (RR: 1.81, 95% CI: 1.29-2.54, P=0.001). These results show that SNPs in the BER pathway can be used as genetic biomarkers to predict those at high risk for GVHD toward whom novel prophylactic strategies could be targeted. PMID- 20574455 TI - Critical molecular pathways in cancer stem cells of chronic myeloid leukemia. AB - Inhibition of BCR-ABL with kinase inhibitors in the treatment of Philadelphia positive (Ph(+)) chronic myeloid leukemia (CML) is highly effective in controlling but not curing the disease. This is largely due to the inability of these kinase inhibitors to kill leukemia stem cells (LSCs) responsible for disease relapse. This stem cell resistance is not associated with the BCR-ABL kinase domain mutations resistant to kinase inhibitors. Development of curative therapies for CML requires the identification of crucial molecular pathways responsible for the survival and self-renewal of LSCs. In this review, we will discuss our current understanding of these crucial molecular pathways in LSCs and the available therapeutic strategies for targeting these stem cells in CML. PMID- 20574457 TI - Retraction. Predicting the site of origin of tumors by a gene expression signature derived from normal tissues. PMID- 20574456 TI - The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling. AB - De-ubiquitinating enzymes (DUBs) can reverse the modifications catalyzed by ubiquitin ligases and as such are believed to be important regulators of a variety of cellular processes. Several members of this protein family have been associated with human cancers; however, there is little evidence for a direct link between deregulated de-ubiquitination and neoplastic transformation. Ubiquitin C-terminal hydrolase (UCH)-L1 is a DUB of unknown function that is overexpressed in several human cancers, but whether it has oncogenic properties has not been established. To address this issue, we generated mice that overexpress UCH-L1 under the control of a ubiquitous promoter. Here, we show that UCH-L1 transgenic mice are prone to malignancy, primarily lymphomas and lung tumors. Furthermore, UCH-L1 overexpression strongly accelerated lymphomagenesis in Emu-myc transgenic mice. Aberrantly expressed UCH-L1 boosts signaling through the Akt pathway by downregulating the antagonistic phosphatase PHLPP1, an event that requires its de-ubiquitinase activity. These data provide the first in vivo evidence for DUB-driven oncogenesis and suggest that UCH-L1 hyperactivity deregulates normal Akt signaling. PMID- 20574459 TI - Succession of methanotrophs in oxygen-methane counter-gradients of flooded rice paddies. AB - Little is known about population dynamics and contribution of specific taxa to methane oxidation in flooded rice paddies. In this article we investigate the succession of methanotrophs in oxygen-methane counter-gradients. We used a gradient microcosm system that simulates oxic-anoxic interfaces of a water saturated paddy soils, and measured pmoA-based (gene encoding particulate methane monooxygenase) terminal restriction fragment length polymorphism (T-RFLP) profiles at both the transcription (mRNA) and the population (DNA) levels. The DNA T-RFLP profiles indicated that the methanotrophic community present clearly differed from the active methanotrophic community. We observed a succession of the methanotrophic community over time without any direct effect of pore water chemistry on the community structure. Both the total population and the active subpopulation changed with time, whereas methane oxidation rates remained nearly constant. Hence, we suggest that a diverse microbial seed bank of methanotrophs is important in maintaining the function in a dynamic ecosystem. PMID- 20574458 TI - Survival of Escherichia coli in the environment: fundamental and public health aspects. AB - In this review, our current understanding of the species Escherichia coli and its persistence in the open environment is examined. E. coli consists of six different subgroups, which are separable by genomic analyses. Strains within each subgroup occupy various ecological niches, and can be broadly characterized by either commensalistic or different pathogenic behaviour. In relevant cases, genomic islands can be pinpointed that underpin the behaviour. Thus, genomic islands of, on the one hand, broad environmental significance, and, on the other hand, virulence, are highlighted in the context of E. coli survival in its niches. A focus is further placed on experimental studies on the survival of the different types of E. coli in soil, manure and water. Overall, the data suggest that E. coli can persist, for varying periods of time, in such terrestrial and aquatic habitats. In particular, the considerable persistence of the pathogenic E. coli O157:H7 is of importance, as its acid tolerance may be expected to confer a fitness asset in the more acidic environments. In this context, the extent to which E. coli interacts with its human/animal host and the organism's survivability in natural environments are compared. In addition, the effect of the diversity and community structure of the indigenous microbiota on the fate of invading E. coli populations in the open environment is discussed. Such a relationship is of importance to our knowledge of both public and environmental health. PMID- 20574460 TI - Vertical structure of small eukaryotes in three lakes that differ by their trophic status: a quantitative approach. AB - In lakes, the diversity of eukaryotic picoplankton has been recently studied by the analysis of 18S ribosomal RNA gene sequences; however, quantitative data are rare. In this study, the vertical structure and abundance of the small eukaryotic size fraction (0.2-5 MUm) were investigated in three lakes by tyramide signal amplification-fluorescent in situ hybridization targeting six phylogenetic groups: Chlorophyta, Haptophyta, Cercozoa, LKM11, Perkinsozoa and fungi. The groups targeted in this study are found in all lakes; however, both the abundance and structure of small eukaryotes are dependent on the system's productivity and depth. These data highlighted the presence of Chlorophyta contributing on an average to 19.3%, 14.7% and 41.2% of total small eukaryotes in lakes Bourget, Aydat and Pavin, respectively. This study also revealed the unexpected importance of Haptophyta, reaching 62.8% of eukaryotes in the euphotic zone of Lake Bourget. The high proportions of these pigmented cells highlight the underestimation of these groups by PCR-based methods. The presence of pigmented Chlorophyta in the deepest zones of the lakes suggests a mixotrophic behaviour of these taxa. We also confirmed the presence of putative parasites such as Perkinsozoa (5.1% of small eukaryotes in Lake Pavin and Bourget) and, with lower abundances, fungi (targeted by the MY1574 probe). Cells targeted by LKM11 probes represented the second group of abundance within heterotrophs. Open questions regarding the functional roles of the targeted groups arise from this study, especially regarding parasitism and mixotrophy, which are interactions poorly taken into account in planktonic food web models. PMID- 20574463 TI - Susan e. Mackinnon, m.d., f.a.C.s. PMID- 20574464 TI - Facial paralysis. PMID- 20574465 TI - A review of facial nerve anatomy. AB - An intimate knowledge of facial nerve anatomy is critical to avoid its inadvertent injury during rhytidectomy, parotidectomy, maxillofacial fracture reduction, and almost any surgery of the head and neck. Injury to the frontal and marginal mandibular branches of the facial nerve in particular can lead to obvious clinical deficits, and areas where these nerves are particularly susceptible to injury have been designated danger zones by previous authors. Assessment of facial nerve function is not limited to its extratemporal anatomy, however, as many clinical deficits originate within its intratemporal and intracranial components. Similarly, the facial nerve cannot be considered an exclusively motor nerve given its contributions to taste, auricular sensation, sympathetic input to the middle meningeal artery, and parasympathetic innervation to the lacrimal, submandibular, and sublingual glands. The constellation of deficits resulting from facial nerve injury is correlated with its complex anatomy to help establish the level of injury, predict recovery, and guide surgical management. PMID- 20574466 TI - Approaches to grading facial nerve function. AB - Systematic evaluation of facial nerve paralysis allows the clinician to determine objectively the severity of disability, record and communicate this information to colleagues, and evaluate response to therapy. An ideal grading system would be precisely calibrated-at once accurate, reliable, and conducive to use in both the clinic and the research laboratory. Developing such a system has proved difficult, however. The complexity of facial nerve anatomy allows tremendous variation in clinical presentation, and assessments of facial expression are inherently subjective in nature. Carefully defined parameters are therefore crucial in performing objective and quantitative analyses. This article reviews the clinical considerations involved in grading facial function and traces the evolution of current approaches. Emphasis is placed upon advances in computer based facial nerve grading. PMID- 20574467 TI - The surgical management of facial nerve injury. AB - The surgical management of facial nerve injuries is dependent upon a thorough understanding of facial nerve anatomy, nerve physiology, and microsurgical techniques. When possible, primary neurorrhaphy is the "gold standard" repair technique. Injuries resulting in long nerve gaps or a significant delay between the time of injury and repair requires alterative techniques, such as nerve grafts, nerve transfers, regional muscle transfers, free tissue transfers, and static procedures. Scrupulous technique, selection of the appropriate surgical management, and aggressive physiotherapy with motor reeducation are all critical to obtaining a functionally and aesthetically acceptable result while minimizing synkinesis and facial asymmetry. This review of the literature provides an overview of current concepts in the surgical management of facial nerve injuries. PMID- 20574468 TI - Ophthalmic management of the facial palsy patient. AB - The management of the ocular sequelae of facial palsy should be individualized for each patient. The patient's age, ocular motility, tear production, and corneal sensation are considered when developing a treatment plan. Individuals with transient weakness often require only therapy with topical lubricants. Permanent or chronic facial paralysis is usually associated with lagophthalmos, ectropion, and exposure keratitis. Both "static" and "dynamic" procedures can be performed to improve these conditions. Combined eyelid surgery and suspension of the midface often provides the best result. However, patients with permanent facial palsy usually suffer chronic ocular symptoms, requiring long-term follow up and continued topical therapy. PMID- 20574469 TI - Mobius syndrome. AB - Mobius syndrome is classically defined as combined congenital bilateral facial and abducens nerve palsies, although it may also be associated with a myriad of other craniofacial, musculoskeletal, cardiothoracic, endocrinologic, and developmental disorders. The problem that most patients complain about, however, is the inability to smile and close their lips while eating. Although the etiology of this syndrome is still unknown, scientific support has been growing for the hypothesis that it is due to an embryological disruption of subclavian artery development. The treatment of choice for facial reanimation in these patients is a neurovascular free muscle transfer, ideally using the gracilis muscle with direct repair of the gracilis muscle's motor nerve to the masseteric branch of the trigeminal nerve. If the masseteric nerve is unavailable, a partial hypoglossal or accessory nerve may be used. These operations, enhanced by the effects of cerebral plasticity, may allow Mobius patients to reach their goals of satisfactory spontaneous smiles. PMID- 20574470 TI - Rehabilitation strategies for facial nerve injuries. AB - Many treatment techniques, including exercise, electrical stimulation, biofeedback, and neuromuscular retraining, have been described for the treatment of patients with facial paresis. The degree of nerve injury determines the recovery of the facial muscles. Patients with a Sunderland third-degree injury benefit most from therapy to maximize facial nerve function. Following a facial nerve palsy, many patients present with facial muscle weakness in addition to aberrant synkinetic movements. Therefore therapy must be directed toward control of voluntary movement and decreasing synkinesis. Neuromuscular reeducation involves selective muscle control to decrease synkinesis and increase muscle excursion. Muscle reeducation using surface electromyographic (EMG) biofeedback and home exercises has been shown to be efficacious in the treatment of facial palsies. Neuromuscular retraining can be beneficial in maximizing facial recovery by initially decreasing aberrant synkinetic muscle activity and then increasing voluntary movement and excursion. PMID- 20574472 TI - Scott L. Spear, m.d., f.a.C.s. And steven p. Davison, m.d., d.d.s., f.a.C.s. PMID- 20574471 TI - Donor nerve selection in facial reanimation surgery. AB - The motor components of local cranial nerves provide a series of options for the surgical rehabilitation of the paralyzed face. Nerve donor sites vary with respect to their motor power, functional deficit, and synergy with facial expression. A thorough understanding of each donor nerve's strengths and weaknesses facilitates the selection process. Technical modifications to reduce donor site morbidity and the emerging role of the masseter nerve are examined. PMID- 20574473 TI - Advances in breast reduction and mastopexy. PMID- 20574474 TI - Breast reshaping after massive weight loss. AB - After massive weight loss, breasts have poor shape, projection, and skin elasticity. The nipples are distorted and ptotic. Mastopexy is difficult and historically includes the use of excess nearby tissues. The senior author reviews his experience with 24 patients over the past 4 years. Body contouring is offered after the weight loss is stable. Breasts may be reshaped by mastopexy and/or augmentation; three examples are presented. More often the breasts are reshaped during an upper body lift. This lift is a reverse abdominoplasty that ends along the inframammary fold scar of the Wise-pattern mastopexy and extends laterally along the back roll. When the breasts need enlargement, nearby discard tissue is used for augmentation. The spiral flap has been devised for that purpose. When more tissue is needed, silicone implants are used. The long inframammary scar of the McKissock vertical bipedicle mastopexy forms the junction between the breast and reverse abdominoplasty. Proper inframammary fold construction is pivotal to the upper body lift. We have successfully combine breast reshaping with upper body lift for this difficult deformity after massive weight loss and present two demonstrative examples. Breast reshaping is best performed during an upper body lift. PMID- 20574475 TI - Simultaneous breast augmentation with periareolar mastopexy. AB - Augmentation mammaplasty is frequently used to fill out the soft tissue envelope of the breast. This is most successful with minimal skin laxity or when there is no need for significant nipple movement. The addition of a periareolar mastopexy can reduce the skin envelope; however, its value is limited to those with no more than mild second-degree ptosis. Although this is a valuable technique, the risks involved with the operation are additive, and, accordingly, patient selection and surgical technique is important. PMID- 20574476 TI - Superomedial pedicle reduction with short scar. AB - Reduction mammaplasty combining a superomedial pedicle with a circumareolar/vertical pattern skin excision avoids an inferior pedicle that can interfere with vertical scar technique, yet it is flexible enough to allow for a short transverse skin excision. This technique is suitable for small to moderate size reductions. PMID- 20574477 TI - Vertical breast reduction. AB - The vertical approach to breast reduction surgery has achieved increasing popularity. The learning curve can be a problem for surgeons starting to incorporate vertical techniques into their practices; the medial pedicle approach is outlined in detail. Designing and creating the medial pedicle is straightforward and rotating it into position is easy. An elegant curve to the lower pole of the reduced breast can thus be created. Current concepts related to the skin brassiere, breast sutures, and the longevity of results are reviewed. It is important for the surgeon to understand that the skin resection pattern and the pedicle design are separate issues when discussing breast reduction surgery. PMID- 20574478 TI - Breast reduction using liposuction alone. AB - Liposuction alone as a treatment of breast hypertrophy has been mentioned in the literature for the past decade but has been limited in its application. Our experience in over 350 cases has shown that liposuction breast reduction is an excellent method of breast reduction when applied to the proper patient. The techniques involved in liposuction breast reduction mirror those used in standard liposuction cases, so most plastic surgeons will find the learning curve for this procedure to be very easy. Complications are infrequent and the recovery is rapid and easy. Liposuction breast reduction affords a rapid procedure with minimal complications and easy recovery and can provide a useful alternative to traditional breast reduction surgery in many patients. PMID- 20574479 TI - The Short Scar Periareolar Inferior Pedicle Reduction (SPAIR) Mammaplasty. AB - Although generally effective, the inverted T inferior pedicle breast reduction technique is associated with continuing concerns over cutaneous scar as well as shape distortion, which can to worsen over time. This article will outline a technique of breast reduction that is also based on an inferior pedicle but manages the skin envelope with a combined periareolar and vertical skin excision. By combining these elements, an effective method of breast reduction is created that reduces the amount of cutaneous scar by half and yet results in an improved and long-lasting breast shape that is stable over time. This method, called the "short scar periareolar inferior pedicle reduction" (or "SPAIR" mammaplasty) is applicable to a wide variety of breast problems ranging from simple ptosis to extremes of macromastia. Aesthetically pleasing results are consistently and reliably obtained with few complications. It is offered as an effective method of reduced scar breast reduction. PMID- 20574480 TI - TRAM Revisions and Contralateral Mammaplasties: The Role of "Mirror Image" Skin Patterns. AB - Symmetry is the sine qua non of breast reconstruction. A symmetrical result offers peace of mind, a healthy body image, and improved self-esteem to the patient and presents a sometimes elusive goal to the plastic surgeon. When symmetry comes with modest effort we are pleased, but more often the effort is prolonged through several operations over a period of time. This article addresses the management of both the reconstructed breast mound(s) as well as the contralateral breast at different stages of the reconstruction process. By approaching the reconstructed breast mound(s) and a remaining native breast as similar soft tissue structures with similar soft tissue envelopes, it may be possible to maximize the symmetry of the final result. PMID- 20574481 TI - Reduction mammaplasty in conjunction with breast conservation. AB - Breast conservation therapy, consisting of lumpectomy or segmental mastectomy with negative margins followed by breast irradiation, has become a standard and safe alternative to mastectomy in selected patients with early-stage breast cancer. As the inclusion criteria for breast conservation therapy have continued to evolve to include lower quadrant tumors, very large breasts, and central tumors, the potential for significant disfigurement after breast conservation therapy has increased. Bilateral reduction mammaplasty in conjunction with tumor directed partial mastectomy is a surgical approach that can benefit these patients by creating symmetric, aesthetically pleasing breasts in a single-stage operation. PMID- 20574482 TI - Geoffrey L. Robb, m.d., f.a.C.s. And Michael j. Miller, m.d., f.a.C.s. PMID- 20574483 TI - A new decade in breast reconstruction. PMID- 20574484 TI - History of breast reconstruction. AB - The treatment of breast cancer has evolved significantly from the original surgical technique described by Halsted. The reconstruction of the breast has also been a large interest among surgeons and patients. The history of breast reconstruction dates back to the 1800s with an attempt to transplant a lipoma to a mastectomy site. Several techniques ranging from the "walking flap" of Gilles to the free perforator flap using autogenous tissue for recreation of a breast "mound" have been established and refined. The use of tissue expanders for breast reconstruction has also been perfected over the last three decades. Breast reconstruction, which was once admonished in the early part of the 20th century, has now become a routine choice for women undergoing breast cancer surgery. PMID- 20574485 TI - Breast reconstruction with tissue expanders and implants: a practical guide to immediate and delayed reconstruction. AB - Breast reconstruction with tissue expanders and implants offers patients satisfying aesthetic results with no donor site morbidity. This article provides a practical guide for successful reconstruction using current techniques and available devices. Preoperative planning is discussed, emphasizing close collaboration with medicial and surgical oncology colleagues. Special concerns regarding adjuvant radiation are also addressed. Intraoperative techniques that optimize the final result are presented, along with a reliable and reasoned approach to the management of complications. Following these guidelines, aesthetically pleasing results with few complications can be obtained consistently. PMID- 20574486 TI - Trends in autologous breast reconstruction. AB - Several trends have influenced autologous breast reconstruction in the last decade. The development of the skin-sparing mastectomy has markedly improved the aesthetic results of autologous breast reconstruction. Modifications have included purse-stringing periareolar incisions and vertical reduction pattern incisions. The increasing use of postmastectomy has had a negative impact on transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction. Delayed reconstruction may be the best option when adjuvant radiation is planned. Careful anatomic studies of the blood supply to the abdominal wall and critical outcome analyses have resulted in many refinements in TRAM flap breast reconstruction. Careful patient selection is critical to avoid complications. Obesity, tobacco smoking, a history of chest wall radiation, and abdominal scars are known risk factors for wound complications. TRAM flap reconstruction should be considered a two-stage procedure regardless of nipple reconstruction. The first stage is building the foundation and framework of the breast. The second stage is essential for final adjustments to the volume, contour, and position of the breast mound. PMID- 20574487 TI - Reconstruction of the breast conservation deformity. AB - The era of breast conserving treatment of early-stage breast carcinoma has created reconstructive challenges for the plastic surgeon. Although good to excellent cosmetic outcomes occur in the majority of patients, a significant number could benefit from additional reconstructive measures. Because of the need for continuing surveillance following breast-conserving therapy, estimated at 5 10% after fifteen years, plastic surgeons should choose techniques that do not interfere with the detection of recurrent breast carcinoma. Myocutaneous flaps-in particular, the latissimus dorsi and transverse rectus abdominis-have fulfilled the reconstructive needs of these patients by providing well-vascularized soft tissue. Postoperative radiological evaluation has demonstrated that these flaps are radiolucent, unlike breast implants that can obscure accurate mammographic interpretation.Myocutaneous flaps have been used for both immediate and delayed reconstruction of post-breast conservation deformities. The delayed approach offers the benefit of an established contour deformity that usually involves cutaneous, parenchymal, and nipple-areolar components. Moderate overcorrection of the defect has been advocated in anticipation of ongoing postradiation wound contraction and fibrosis. Immediate reconstruction of lumpectomy and partial mastectomy defects permits wider initial excision of the breast lesion, but can be compromised by positive histological margins. Long-term results suggest stability of the aesthetic outcome following reconstruction of delayed deformities. PMID- 20574488 TI - Update on Breast Reconstruction Using Free TRAM, DIEP, and SIEA Flaps. AB - Breast reconstruction using autologous tissue is commonly accomplished using the transverse rectus abdominis myocutaneous (TRAM) flap. The establishment of microvascular surgery led to the development of the free TRAM flap because of its increased vascularity and decreased rectus abdominis sacrifice. The muscle sparing free TRAM, DIEP, and SIEA flap techniques followed in an effort to decrease abdominal donor site morbidity by decreasing injury to the rectus abdominis muscle and fascia. Data have accumulated over the past decade that show that muscle- and fascia-sparing techniques, such as the use of DIEP flaps, result in measurably better postoperative abdominal strength. However, muscle-sparing techniques do not appear to decrease the risk of abdominal bulging or hernia, and there are no significant differences in patient-reported abdominal weakness or functional impairments. The SIEA flap is presented as a reemerging method that can virtually eliminate abdominal donor site morbidity. Sensory nerve coaptation to improve reconstructed breast sensation is also reviewed. PMID- 20574489 TI - Breast reconstruction and adjuvant therapies. AB - Recent developments in the management of breast cancer have increased the complexity of planning for immediate breast reconstruction. Two recent trials have demonstrated superior locoregional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of postmastectomy radiation therapy (XRT) to mastectomy and chemotherapy. On the basis of these results, the use of postmastectomy XRT in patients with early stage breast cancer is increasing. Unfortunately, it is difficult to predict the presence or extent of axillary lymph node involvement-a major determinant of the need for postmastectomy XRT-before mastectomy. There are two potential problems with performing an immediate breast reconstruction in a patient who will require postmastectomy XRT. First, postmastectomy XRT can adversely affect the aesthetic outcome of an immediate breast reconstruction. Second, an immediate breast reconstruction can interfere with the delivery of postmastectomy XRT. Chemotherapy before or after reconstruction does not significantly increase the occurrence of wound-healing problems and breast reconstruction does not appear to delay the initiation or resumption of chemotherapy. The increasing use of postmastectomy XRT and chemotherapy in patients with early-stage breast cancer necessitates increased communication between the medical oncologist, radiation oncologist, breast surgeon, and plastic surgeon during treatment planning for these patients. PMID- 20574490 TI - Chest wall reconstruction and advanced disease. AB - Clinical experience supports a role for palliative procedures in patients with locally advanced or recurrent breast cancer, yet numerous challenges are entailed in both the extirpation and reconstruction of the chest wall in these cases. The defects may be profound and complicated by prior surgery, radiation therapy, or patient-related variables. The reconstructive techniques employed must neither encumber nor delay any necessary postoperative therapy and must not result in unacceptable morbidity or compromise quality of life. Our surgical approach to these cases incorporates a team of specialists from a broad spectrum of medical and surgical disciplines. Each operative plan is tailored to the specific needs and requirements of the individual patient. PMID- 20574491 TI - Breast reconstruction and psychosocial adjustment: what have we learned and where do we go from here? AB - For women with breast cancer, there are many treatment options, with surgery often the primary treatment for early-stage disease. An increasing number of women are choosing to have reconstruction following their mastectomies. Both surgical and medical treatments for breast cancer are increasingly evaluated not only on the basis of their safety and medical outcomes but also their impact on women's psychosocial and quality of life (QOL). The objective of this article is to describe current knowledge regarding the psychosocial adjustment of women undergoing reconstruction, identify limitations in the existing literature, and offer suggestions for the direction of future work in this area. Though most studies have found comparable general QOL in women who have different surgical treatments for breast cancer, some research suggests that reconstruction may provide benefits in terms of body image and sexuality, especially compared with women who have mastectomies only. Most of the existing studies have failed to consider the potential importance of demographic- and treatment-related variables on women's psychosocial adjustment. As reconstruction procedures continue to be developed and refined, the impact of these procedures on women's short- and long term psychosocial adjustment and QOL is needed. PMID- 20574492 TI - Patient education and decision making in breast reconstruction. AB - A well-informed patient who actively participates in decision making is an essential ingredient of successful outcome in breast reconstruction. The plastic surgeon must be prepared to answer all the patient's questions in a clear and concise manner. All women considering breast reconstruction need to understand the rationale for reconstruction and have realistic expectations for what can be accomplished. They need to consider the optimal timing and the advantages and disadvantages of each technical option. The patient education process can be enhanced by the thoughtful inclusion of growing set of educational tools and decision aids. This article reviews each of these issues and suggests a way to organize and present the essential material in a way that has proven effective with women in our practice. PMID- 20574493 TI - Breast reconstruction practices in north america: current trends and future priorities. AB - The Women's Health and Cancer Rights Act (WHCRA) became federal law on January 1, 1999, mandating health care payer coverage for postmastectomy breast reconstruction. Despite passage of this legislation, breast reconstruction rates in the United States remain low. The Surveillance, Epidemiology and End Results (SEER) database for mastectomy patients in 11 regions across the United States show overall rates for immediate and early delayed reconstruction (performed within 4 months of mastectomy) of 15.4% for 1998 and 18.0% for 2000. Reconstruction rates vary significantly by region as well as by patient age, race, and income. The paper examines potential etiologies for low utilization of breast reconstruction and outlines possible remedies. PMID- 20574495 TI - Advances in GERD: Current Developments in the Management of Acid-Related GI Disorders. PMID- 20574494 TI - Breast reconstruction in private practice. AB - Comprehensive breast reconstruction can be performed in private practice. Our practice philosophy is that autogenous tissue provides the best substrate for breast reconstruction; the deep inferior epigastric perforator flap is our primary method of breast reconstruction. Microsurgical training and a group practice model permit routine use of all autogenous tissue techniques. Office, operating room, and hospital teams must be assembled; these teams follow clinical pathways, which make the execution of reconstructive procedures consistent and efficient. The practice must implement a plan for physician and patient education. The practice must review clinical outcomes, making adjustments in operative techniques and pre- and postoperative clinical pathways so that the best results can be achieved with a low complication rate. Breast reconstruction is a core service of our practice. We have accrued an economy of scale including these features: intraoperative and clinical efficiency, low practice overhead costs, and a high patient satisfaction rate. PMID- 20574496 TI - Advances in endoscopy: current developments in diagnostic and therapeutic endoscopy. PMID- 20574497 TI - Advances in IBD: Current Developments in the Treatment of Inflammatory Bowel Diseases. PMID- 20574498 TI - Gastro-hep news: recent clinical findings. PMID- 20574499 TI - Advances in hepatology: current developments in the treatment of hepatitis and hepatobiliary disease. PMID- 20574501 TI - Collagenous sprue: a distinctive and heterogeneous clinicopathologic disorder. PMID- 20574500 TI - Collagenous sprue: a case report and literature review. PMID- 20574502 TI - Ulcerative colitis presenting as acute pancreatitis in a 6-year-old patient. PMID- 20574503 TI - Acute pancreatitis: an emerging presentation for autoimmune pancreatitis in patients with inflammatory bowel disease. PMID- 20574504 TI - Low-dose nocturnal tegaserod or erythromycin delays symptom recurrence after treatment of irritable bowel syndrome based on presumed bacterial overgrowth. AB - Our group previously demonstrated a deficiency of migrating motor complexes in irritable bowel syndrome (IBS) patients with small intestinal bacterial overgrowth (SIBO). Based on disturbed fasting motility, we tested whether low dose nocturnal erythromycin or tegaserod can prevent the recurrence of IBS symptoms after successful antibiotic treatment. METHODS: 203 patient charts were reviewed to find IBS patients with SIBO, and treatment cycles were assessed to identify subjects with clinical and breath test resolution. The charts of those who met the inclusion criteria were reviewed to determine the method of prevention of symptom recurrence and the length of remission. The two preventive agents used were erythromycin (50 mg) or tegaserod (2-6 mg) orally at bedtime. RESULTS: 64 patients met the inclusion criteria. Subjects receiving no prevention (n=6) after successful antibiotic treatment experienced symptom recurrence after 59.7+/-47.4 days. Prevention using erythromycin (n=42) demonstrated 138.5+/-132.2 symptom-free days (P=.08 vs no prevention) compared to 241.6+/-162.2 days with tegaserod (n=16; P=.003 vs no prevention; P=.004 vs erythromycin). Switching from erythromycin to tegaserod (n=20) extended resolution from 105.8+/-73.3 days to 199.7+/-162.9 days (P=.04). Changing from no therapy to erythromycin or tegaserod (n=6) extended recurrence from 41.0+/-44.8 days to 195.6+/-153.5 days (P=.06). CONCLUSION: Tegaserod significantly prevents the recurrence of IBS symptoms after antibiotic treatment compared to erythromycin or no prevention. PMID- 20574505 TI - Recent advances in liver transplantation for the practicing gastroenterologist. AB - Liver transplantation is the definitive therapy for end-stage liver disease of various etiologies as well as acute liver failure and early-stage hepatocellular carcinoma. The Model for End-Stage Liver Disease (MELD) score is essential for organ allocation in the United States. Addition of the serum sodium level to the MELD score is a recent development that helps prognosticate cirrhotic patients with hyponatremia, a commonly seen manifestation of end-stage liver disease. The currently used Milan criteria for hepatocellular carcinoma have been expanded with some success at certain transplant centers, and tumor downstaging prior to transplant is being used more frequently. The tremendous shortage of donor organs continues to be the major limitation of this life-saving therapy. This has led to the use of extended-criteria donors, donation after cardiac death, split liver grafts, and live donor liver transplants. Renal dysfunction following liver transplant requires close monitoring and dose adjustments of immunosuppressive medications. Although most liver transplants in the United States are for chronic hepatitis C infection and its sequelae, hepatitis C virus recurrence is a common problem that is challenging to treat in the post-transplant population. PMID- 20574506 TI - Emerging issues in ulcerative colitis and ulcerative proctitis: individualizing treatment to maximize outcomes. PMID- 20574511 TI - Smooth pursuit eye movements improve temporal resolution for color perception. AB - Human observers see a single mixed color (yellow) when different colors (red and green) rapidly alternate. Accumulating evidence suggests that the critical temporal frequency beyond which chromatic fusion occurs does not simply reflect the temporal limit of peripheral encoding. However, it remains poorly understood how the central processing controls the fusion frequency. Here we show that the fusion frequency can be elevated by extra-retinal signals during smooth pursuit. This eye movement can keep the image of a moving target in the fovea, but it also introduces a backward retinal sweep of the stationary background pattern. We found that the fusion frequency was higher when retinal color changes were generated by pursuit-induced background motions than when the same retinal color changes were generated by object motions during eye fixation. This temporal improvement cannot be ascribed to a general increase in contrast gain of specific neural mechanisms during pursuit, since the improvement was not observed with a pattern flickering without changing position on the retina or with a pattern moving in the direction opposite to the background motion during pursuit. Our findings indicate that chromatic fusion is controlled by a cortical mechanism that suppresses motion blur. A plausible mechanism is that eye-movement signals change spatiotemporal trajectories along which color signals are integrated so as to reduce chromatic integration at the same locations (i.e., along stationary trajectories) on the retina that normally causes retinal blur during fixation. PMID- 20574512 TI - Concurrent helminthic infection protects schoolchildren with Plasmodium vivax from anemia. AB - BACKGROUND: Plasmodium vivax is responsible for a significant portion of malaria cases worldwide, especially in Asia and Latin America, where geo-helminthiasis have a high prevalence. Impact of the interaction between vivax malaria and intestinal helminthes has been poorly explored. The objective of this study was to evaluate the influence of intestinal helminthiasis on the concentration of hemoglobin in children with Plasmodium vivax malaria in rural areas in the municipality of Careiro, in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: A cohort study was conducted from April to November 2008, enrolling children from 5 to 14 years old in two rural areas endemic for malaria. A cross sectional evaluation was performed in April to actively detect cases of malaria and document baseline hemoglobin and nutritional status. Children were followed up for six months through passive case detection of malaria based on light microscopy. Throughout the follow-up interval, hemoglobin value and stool examination (three samples on alternate days) were performed on children who developed P. vivax malaria. For 54 schoolchildren with a single infection by P. vivax, hemoglobin during the malaria episode was similar to the baseline hemoglobin for children co-infected with Ascaris lumbricoides (n = 18), hookworm (n = 11) and Trichuris trichiura (n = 9). In children without intestinal helminthes, a significant decrease in the hemoglobin during the malarial attack was seen as compared to the baseline concentration. In the survival analysis, no difference was seen in the time (in days) from the baseline cross-sectional to the first malarial infection, between parasitized and non-parasitized children. CONCLUSION/SIGNIFICANCE: For the first time, a cohort study showed that intestinal helminthes protect against hemoglobin decrease during an acute malarial attack by P. vivax. PMID- 20574513 TI - Systematic analysis of cis-elements in unstable mRNAs demonstrates that CUGBP1 is a key regulator of mRNA decay in muscle cells. AB - BACKGROUND: Dramatic changes in gene expression occur in response to extracellular stimuli and during differentiation. Although transcriptional effects are important, alterations in mRNA decay also play a major role in achieving rapid and massive changes in mRNA abundance. Moreover, just as transcription factor activity varies between different cell types, the factors influencing mRNA decay are also cell-type specific. PRINCIPAL FINDINGS: We have established the rates of decay for over 7000 transcripts expressed in mouse C2C12 myoblasts. We found that GU-rich (GRE) and AU-rich (ARE) elements are over represented in the 3'UTRs of short-lived mRNAs and that these mRNAs tend to encode factors involved in cell cycle and transcription regulation. Stabilizing elements were also identified. By comparing mRNA decay rates in C2C12 cells with those previously measured for pluripotent and differentiating embryonic stem (ES) cells, we identified several groups of transcripts that exhibit cell-type specific decay rates. Further, whereas in C2C12 cells the impact of GREs on mRNA decay appears to be greater than that of AREs, AREs are more significant in ES cells, supporting the idea that cis elements make a cell-specific contribution to mRNA stability. GREs are recognized by CUGBP1, an RNA-binding protein and instability factor whose function is affected in several neuromuscular diseases. We therefore utilized RNA immunoprecipitation followed by microarray (RIP-Chip) to identify CUGBP1-associated transcripts. These mRNAs also showed dramatic enrichment of GREs in their 3'UTRs and encode proteins linked with cell cycle, and intracellular transport. Interestingly several CUGBP1 substrate mRNAs, including those encoding the myogenic transcription factors Myod1 and Myog, are also bound by the stabilizing factor HuR in C2C12 cells. Finally, we show that several CUGBP1-associated mRNAs containing 3'UTR GREs, including Myod1, are stabilized in cells depleted of CUGBP1, consistent with the role of CUGBP1 as a destabilizing factor. CONCLUSIONS: Taken together, our results systematically establish cis-acting determinants of mRNA decay rates in C2C12 myoblast cells and demonstrate that CUGBP1 associates with GREs to regulate decay of a wide range of mRNAs including several that are critical for muscle development. PMID- 20574514 TI - Deathly drool: evolutionary and ecological basis of septic bacteria in Komodo dragon mouths. AB - Komodo dragons, the world's largest lizard, dispatch their large ungulate prey by biting and tearing flesh. If a prey escapes, oral bacteria inoculated into the wound reputedly induce a sepsis that augments later prey capture by the same or other lizards. However, the ecological and evolutionary basis of sepsis in Komodo prey acquisition is controversial. Two models have been proposed. The "bacteria as venom" model postulates that the oral flora directly benefits the lizard in prey capture irrespective of any benefit to the bacteria. The "passive acquisition" model is that the oral flora of lizards reflects the bacteria found in carrion and sick prey, with no relevance to the ability to induce sepsis in subsequent prey. A third model is proposed and analyzed here, the "lizard-lizard epidemic" model. In this model, bacteria are spread indirectly from one lizard mouth to another. Prey escaping an initial attack act as vectors in infecting new lizards. This model requires specific life history characteristics and ways to refute the model based on these characteristics are proposed and tested. Dragon life histories (some details of which are reported here) prove remarkably consistent with the model, especially that multiple, unrelated lizards feed communally on large carcasses and that escaping, wounded prey are ultimately fed on by other lizards. The identities and evolutionary histories of bacteria in the oral flora may yield the most useful additional insights for further testing the epidemic model and can now be obtained with new technologies. PMID- 20574516 TI - A low molecular weight heparin inhibits experimental metastasis in mice independently of the endothelial glycocalyx. AB - BACKGROUND: Some low molecular weight heparins (LMWHs) prolong survival of cancer patients and inhibit experimental metastasis. The underlying mechanisms are still not clear but it has been suggested that LMWHs (at least in part) limit metastasis by preventing cancer cell-induced destruction of the endothelial glycocalyx. METHODOLOGY/PRINCIPAL FINDINGS: To prove or refute this hypothesis, we determined the net effects of the endothelial glycocalyx in cancer cell extravasation and we assessed the anti-metastatic effect of a clinically used LMWH in the presence and absence of an intact endothelial glycocalyx. We show that both exogenous enzymatic degradation as well as endogenous genetic modification of the endothelial glycocalyx decreased pulmonary tumor formation in a murine experimental metastasis model. Moreover, LMWH administration significantly reduced the number of pulmonary tumor foci and thus experimental metastasis both in the presence or absence of an intact endothelial glycocalyx. CONCLUSIONS: In summary, this paper shows that the net effect of the endothelial glycocalyx enhances experimental metastasis and that a LMWH does not limit experimental metastasis by a process involving the endothelial glycocalyx. PMID- 20574515 TI - Sub-Saharan Africa's mothers, newborns, and children: how many lives could be saved with targeted health interventions? PMID- 20574517 TI - MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. AB - BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate cell homeostasis by inhibiting translation or degrading mRNA of target genes, and thereby can act as tumor suppressor genes or oncogenes. The role of microRNAs in medulloblastoma has only recently been addressed. We hypothesized that microRNAs differentially expressed during normal CNS development might be abnormally regulated in medulloblastoma and are functionally important for medulloblastoma cell growth. METHODOLOGY AND PRINCIPAL FINDINGS: We examined the expression of microRNAs in medulloblastoma and then investigated the functional role of one specific one, miR-128a, in regulating medulloblastoma cell growth. We found that many microRNAs associated with normal neuronal differentiation are significantly down regulated in medulloblastoma. One of these, miR-128a, inhibits growth of medulloblastoma cells by targeting the Bmi-1 oncogene. In addition, miR-128a alters the intracellular redox state of the tumor cells and promotes cellular senescence. CONCLUSIONS AND SIGNIFICANCE: Here we report the novel regulation of reactive oxygen species (ROS) by microRNA 128a via the specific inhibition of the Bmi-1 oncogene. We demonstrate that miR-128a has growth suppressive activity in medulloblastoma and that this activity is partially mediated by targeting Bmi-1. This data has implications for the modulation of redox states in cancer stem cells, which are thought to be resistant to therapy due to their low ROS states. PMID- 20574518 TI - Receptor specificity and transmission of H2N2 subtype viruses isolated from the pandemic of 1957. AB - Influenza viruses of the H2N2 subtype have not circulated among humans in over 40 years. The occasional isolation of avian H2 strains from swine and avian species coupled with waning population immunity to H2 hemagglutinin (HA) warrants investigation of this subtype due to its pandemic potential. In this study we examined the transmissibility of representative human H2N2 viruses, A/Albany/6/58 (Alb/58) and A/El Salvador/2/57 (ElSalv/57), isolated during the 1957/58 pandemic, in the ferret model. The receptor binding properties of these H2N2 viruses was analyzed using dose-dependent direct glycan array-binding assays. Alb/58 virus, which contains the 226L/228S amino acid combination in the HA and displayed dual binding to both alpha 2,6 and alpha 2,3 glycan receptors, transmitted efficiently to naive ferrets by respiratory droplets. Inefficient transmission was observed with ElSalv/57 virus, which contains the 226Q/228G amino acid combination and preferentially binds alpha 2,3 over alpha 2,6 glycan receptors. However, a unique transmission event with the ElSalv/57 virus occurred which produced a 226L/228G H2N2 natural variant virus that displayed an increase in binding specificity to alpha 2,6 glycan receptors and enhanced respiratory droplet transmissibility. Our studies provide a correlation between binding affinity to glycan receptors with terminal alpha 2,6-linked sialic acid and the efficiency of respiratory droplet transmission for pandemic H2N2 influenza viruses. PMID- 20574519 TI - The early nutritional environment of mice determines the capacity for adipose tissue expansion by modulating genes of caveolae structure. AB - While the phenomenon linking the early nutritional environment to disease susceptibility exists in many mammalian species, the underlying mechanisms are unknown. We hypothesized that nutritional programming is a variable quantitative state of gene expression, fixed by the state of energy balance in the neonate, that waxes and wanes in the adult animal in response to changes in energy balance. We tested this hypothesis with an experiment, based upon global gene expression, to identify networks of genes in which expression patterns in inguinal fat of mice have been altered by the nutritional environment during early post-natal development. The effects of over- and under-nutrition on adiposity and gene expression phenotypes were assessed at 5, 10, 21 days of age and in adult C57Bl/6J mice fed chow followed by high fat diet for 8 weeks. Under nutrition severely suppressed plasma insulin and leptin during lactation and diet induced obesity in adult mice, whereas over-nourished mice were phenotypically indistinguishable from those on a control diet. Food intake was not affected by under- or over-nutrition. Microarray gene expression data revealed a major class of genes encoding proteins of the caveolae and cytoskeleton, including Cav1, Cav2, Ptrf (Cavin1), Ldlr, Vldlr and Mest, that were highly associated with adipose tissue expansion in 10 day-old mice during the dynamic phase of inguinal fat development and in adult animals exposed to an obesogenic environment. In conclusion gene expression profiles, fat mass and adipocyte size in 10 day old mice predicted similar phenotypes in adult mice with variable diet-induced obesity. These results are supported by phenotypes of KO mice and suggest that when an animal enters a state of positive energy balance adipose tissue expansion is initiated by coordinate changes in mRNA levels for proteins required for modulating the structure of the caveolae to maximize the capacity of the adipocyte for lipid storage. PMID- 20574520 TI - Maternal health: time to deliver. PMID- 20574521 TI - Conformational determinants of phosphotyrosine peptides complexed with the Src SH2 domain. AB - The inhibition of specific SH2 domain mediated protein-protein interactions as an effective chemotherapeutic approach in the treatment of diseases remains a challenge. That different conformations of peptide-ligands are preferred by different SH2 domains is an underappreciated observation from the structural analysis of phosphotyrosine peptide binding to SH2 domains that may aid in future drug design. To explore the nature of ligand binding, we use simulated annealing (SA) to sample the conformational space of phosphotyrosine-containing peptides complexed with the Src SH2 domain. While in good agreement with the crystallographic and NMR studies of high-affinity phosphopeptide-SH2 domain complexes, the results suggest that the structural basis for phopsphopeptide- Src SH2 interactions is more complex than the "two-pronged plug two-hole socket" model. A systematic study of peptides of type pYEEX, where pY is phosphotyrosine and X is a hydrophobic residue, indicates that these peptides can assume two conformations, one extended and one helical, representing the balance between the interaction of residue X with the hydrophobic hole on the surface of the Src SH2 domain, and its contribution to the inherent tendency of the two glutamic acids to form an alpha-helix. In contrast, a beta-turn conformation, almost identical to that observed in the crystal structure of pYVNV bound to the Grb2 SH2 domain, predominates for pYXNX peptides, even in the presence of isoleucine at the third position. While peptide binding affinities, as measured by fluorescence polarization, correlate with the relative proportion of extended peptide conformation, these results suggest a model where all three residues C-terminal to the phosphotyrosine determine the conformation of the bound phosphopeptide. The information obtained in this work can be used in the design of specific SH2 domain inhibitors. PMID- 20574522 TI - Linear and branched glyco-lipopeptide vaccines follow distinct cross-presentation pathways and generate different magnitudes of antitumor immunity. AB - BACKGROUND: Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined. METHODS/PRINCIPAL FINDINGS: We have constructed two structural analogues of HER-2 glyco-lipopeptide (HER-GLP) by synthesizing a chimeric peptide made of one universal CD4(+) epitope (PADRE) and one HER-2 CD8(+) T-cell epitope (HER(420 429)). The C-terminal end of the resulting CD4-CD8 chimeric peptide was coupled to a tumor carbohydrate B-cell epitope, based on a regioselectively addressable functionalized templates (RAFT), made of four alpha-GalNAc molecules. The resulting HER glyco-peptide (HER-GP) was then linked to a palmitic acid moiety, attached either at the N-terminal end (linear HER-GLP-1) or in the middle between the CD4+ and CD8+ T cell epitopes (branched HER-GLP-2). We have investigated the uptake, processing and cross-presentation pathways of the two HER-GLP vaccine constructs, and assessed whether the position of linkage of the lipid moiety would affect the B- and T-cell immunogenicity and protective efficacy. Immunization of mice revealed that the linear HER-GLP-1 induced a stronger and longer lasting HER(420-429)-specific IFN-gamma producing CD8(+) T cell response, while the branched HER-GLP-2 induced a stronger tumor-specific IgG response. The linear HER-GLP-1 was taken up easily by dendritic cells (DCs), induced stronger DCs maturation and produced a potent TLR- 2-dependent T-cell activation. The linear and branched HER-GLP molecules appeared to follow two different cross presentation pathways. While regression of established tumors was induced by both linear HER-GLP-1 and branched HER-GLP-2, the inhibition of tumor growth was significantly higher in HER-GLP-1 immunized mice (p<0.005). SIGNIFICANCE: These findings have important implications for the development of effective GLP based immunotherapeutic strategies against cancers. PMID- 20574523 TI - Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing. AB - Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in non-coding regions, such as 3'UTRs, 5'UTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain. It was shown that editing levels within protein-coding regions are increased during embryogenesis and after birth and that RNA editing is crucial for organism viability as well as for normal development. In this study we characterized the A-to-I RNA editing phenomenon during neuronal and spontaneous differentiation of human embryonic stem cells (hESCs). We identified high editing levels of Alu repetitive elements in hESCs and demonstrated a global decrease in editing levels of non-coding Alu sites when hESCs are differentiating, particularly into the neural lineage. Using RNA interference, we showed that the elevated editing levels of Alu elements in undifferentiated hESCs are highly dependent on ADAR1. DNA microarray analysis showed that ADAR1 knockdown has a global effect on gene expression in hESCs and leads to a significant increase in RNA expression levels of genes involved in differentiation and development processes, including neurogenesis. Taken together, we speculate that A-to-I editing of Alu sequences plays a role in the regulation of hESC early differentiation decisions. PMID- 20574525 TI - Proteomics-based systems biology modeling of bovine germinal vesicle stage oocyte and cumulus cell interaction. AB - BACKGROUND: Oocytes are the female gametes which establish the program of life after fertilization. Interactions between oocyte and the surrounding cumulus cells at germinal vesicle (GV) stage are considered essential for proper maturation or 'programming' of oocytes, which is crucial for normal fertilization and embryonic development. However, despite its importance, little is known about the molecular events and pathways involved in this bidirectional communication. METHODOLOGY/PRINCIPAL FINDINGS: We used differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) on bovine GV oocyte and cumulus cells and identified 811 and 1247 proteins in GV oocyte and cumulus cells, respectively; 371 proteins were significantly differentially expressed between each cell type. Systems biology modeling, which included Gene Ontology (GO) and canonical genetic pathway analysis, showed that cumulus cells have higher expression of proteins involved in cell communication, generation of precursor metabolites and energy, as well as transport than GV oocytes. Our data also suggests a hypothesis that oocytes may depend on the presence of cumulus cells to generate specific cellular signals to coordinate their growth and maturation. CONCLUSIONS/SIGNIFICANCE: Systems biology modeling of bovine oocytes and cumulus cells in the context of GO and protein interaction networks identified the signaling pathways associated with the proteins involved in cell to-cell signaling biological process that may have implications in oocyte competence and maturation. This first comprehensive systems biology modeling of bovine oocytes and cumulus cell proteomes not only provides a foundation for signaling and cell physiology at the GV stage of oocyte development, but are also valuable for comparative studies of other stages of oocyte development at the molecular level. PMID- 20574524 TI - Sub-Saharan Africa's mothers, newborns, and children: where and why do they die? PMID- 20574526 TI - The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development. AB - Epithelia often show, in addition to the ubiquitous apico-basal (A/B) axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP) is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost) all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus) were first identified in mammals and bind to the Galphai GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s) of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development. PMID- 20574528 TI - Face coding is bilateral in the female brain. AB - BACKGROUND: It is currently believed that face processing predominantly activates the right hemisphere in humans, but available literature is very inconsistent. METHODOLOGY/PRINCIPAL FINDINGS: In this study, ERPs were recorded in 50 right handed women and men in response to 390 faces (of different age and sex), and 130 technological objects. Results showed no sex difference in the amplitude of N170 to objects; a much larger face-specific response over the right hemisphere in men, and a bilateral response in women; a lack of face-age coding effect over the left hemisphere in men, with no differences in N170 to faces as a function of age; a significant bilateral face-age coding effect in women. CONCLUSIONS/SIGNIFICANCE: LORETA reconstruction showed a significant left and right asymmetry in the activation of the fusiform gyrus (BA19), in women and men, respectively. The present data reveal a lesser degree of lateralization of brain functions related to face coding in women than men. In this light, they may provide an explanation of the inconsistencies in the available literature concerning the asymmetric activity of left and right occipito-temporal cortices devoted to face perception during processing of face identity, structure, familiarity or affective content. PMID- 20574527 TI - Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells. AB - BACKGROUND: The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF) 1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation. PRINCIPAL FINDINGS: Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels. CONCLUSIONS: In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF 1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability. PMID- 20574529 TI - The potential involvement of E-cadherin and beta-catenins in meningioma. AB - OBJECTIVE: To investigate the potential involvements of E-cadherin and beta catenin in meningioma. METHODS: Immunohistochemistry staining was performed on samples from patients with meningioma. The results were graded according to the positive ratio and intensity of tissue immunoreactivity. The expression of E cadherin and beta-catenin in meningioma was analyzed by its relationship with WHO2007 grading, invasion, peritumoral edema and postoperative recurrence. RESULTS: The positive rates of E-cadherin in meningioma WHO I, II, III were 92.69%, 33.33% and 0, respectively, (P<0.05); while the positive rates of beta catenin in meningioma WHO I, II, III were 82.93%, 33.33% and 20.00%, respectively, (P<0.05). The positive rate of E-cadherin in meningioma without invasion (94.12%) was higher than that with invasion (46.67%) (P<0.05). The difference in the positive rate of beta-catenin between meningioma without invasion (88.24%) and meningioma with invasion (33.33%, P<0.05) was also statically significant. The positive rates of E-cadherin in meningioma with peritumoral edema 0, 1, 2, 3 were 93.75%, 85.71%, 60.00% and 0 respectively, (P<0.05); the positive rates of beta-catenin in meningioma with peritumoral edema 0, 1, 2, 3 were 87.50%, 85.71%, 30.00% and 0 respectively, (P<0.01). The positive rates of E- cadherin in meningioma with postoperative recurrence were 33.33%, and the positive rate with postoperative non-recurrence was 90.00% (P<0.01). The positive rates of beta-catenin in meningioma with postoperative recurrence and non-recurrence were 11.11%, 85.00%, respectively (P<0.01). CONCLUSION: The expression levels of E- cadherin and beta-catenin correlated closely to the WHO 2007 grading criteria for meningioma. In atypical or malignant meningioma, the expression levels of E-cadherin and beta-catenin were significantly lower. The expression levels of E- cadherin and beta-catenin were also closely correlated with the invasion status of meningioma, the size of the peritumoral edema and the recurrent probabilities of the meningioma, all in an inverse correlationship. Taken together, the present study provided novel molecular targets in clinical treatments to meningioma. PMID- 20574530 TI - Functional and molecular effects of arginine butyrate and prednisone on muscle and heart in the mdx mouse model of Duchenne Muscular Dystrophy. AB - BACKGROUND: The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD) is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated) mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy. CONCLUSIONS/SIGNIFICANCE: These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity. PMID- 20574531 TI - The tetraspanins CD9 and CD81 regulate CD9P1-induced effects on cell migration. AB - CD9P-1 is a cell surface protein with immunoglobulin domains and an unknown function that specifically associates with tetraspanins CD9 and CD81. Overexpression of CD9P-1 in HEK-293 cells induces dramatic changes in cell spreading and migration on various matrices. Experiments using time-lapse videomicroscopy revealed that CD9P-1 expression has led to higher cell motility on collagen I but lower motility on fibronectin through a beta1-integrins dependent mechanism. On collagen I, the increase in cell motility induced by CD9P 1 expression was found to involve integrin alpha2beta1 and CD9P-1 was observed to associate with this collagen receptor. The generation of CD9P-1 mutants demonstrated that the transmembrane and the cytoplasmic domains are necessary for inducing effects on cell motility. On the other hand, expression of tetraspanins CD9 or CD81 was shown to reverse the effects of CD9P-1 on cell motility on collagen I or fibronectin with a concomitant association with CD9P-1. Thus, the ratio of expression levels between CD9P-1 and its tetraspanin partners can regulate cell motility. PMID- 20574532 TI - Intermediate phenotypes identify divergent pathways to Alzheimer's disease. AB - BACKGROUND: Recent genetic studies have identified a growing number of loci with suggestive evidence of association with susceptibility to Alzheimer's disease (AD). However, little is known of the role of these candidate genes in influencing intermediate phenotypes associated with a diagnosis of AD, including cognitive decline or AD neuropathologic burden. METHODS/PRINCIPAL FINDINGS: Thirty-two single nucleotide polymorphisms (SNPs) previously implicated in AD susceptibility were genotyped in 414 subjects with both annual clinical evaluation and completed brain autopsies from the Religious Orders Study and the Rush Memory and Aging Project. Regression analyses evaluated the relation of SNP genotypes to continuous measures of AD neuropathology and cognitive function proximate to death. A SNP in the zinc finger protein 224 gene (ZNF224, rs3746319) was associated with both global AD neuropathology (p = 0.009) and global cognition (p = 0.002); whereas, a SNP at the phosphoenolpyruvate carboxykinase locus (PCK1, rs8192708) was selectively associated with global cognition (p = 3.57 x 10(-4)). The association of ZNF224 with cognitive impairment was mediated by neurofibrillary tangles, whereas PCK1 largely influenced cognition independent of AD pathology, as well as Lewy bodies and infarcts. CONCLUSIONS/SIGNIFICANCE: The findings support the association of several loci with AD, and suggest how intermediate phenotypes can enhance analysis of susceptibility loci in this complex genetic disorder. PMID- 20574533 TI - Caffeine prevents transcription inhibition and P-TEFb/7SK dissociation following UV-induced DNA damage. AB - BACKGROUND: The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing. METHODOLOGY/PRINCIPAL FINDINGS: We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3 kinase-related protein kinases, because inhibition of phosphatidylinositol 3 kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage. CONCLUSION/SIGNIFICANCE: Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated. PMID- 20574534 TI - Relationships of the location and content of rounds to specialty, institution, patient-census, and team size. AB - OBJECTIVE: Existing observational data describing rounds in teaching hospitals are 15 years old, predate duty-hour regulations, are limited to one institution, and do not include pediatrics. We sought to evaluate the effect of medical specialty, institution, patient-census, and team participants upon time at the bedside and education occurring on rounds. METHODS AND PARTICIPANTS: Between December of 2007 and October of 2008 we performed 51 observations at Lucile Packard Children's Hospital, Seattle Children's Hospital, Stanford University Hospital, and the University of Washington Medical Center of 35 attending physicians. We recorded minutes spent on rounds in three location and seven activity categories, members of the care team, and patient-census. RESULTS: Results presented are means. Pediatric rounds had more participants (8.2 vs. 4.1 physicians, p<.001; 11.9 vs. 2.4 non-physicians, p<.001) who spent more minutes in hallways (96.9 min vs. 35.2 min, p<.001), fewer minutes at the bedside (14.6 vs. 38.2 min, p = .01) than internal medicine rounds. Multivariate regression modeling revealed that minutes at the bedside per patient was negatively associated with pediatrics (-2.77 adjusted bedside minutes; 95% CI -4.61 to 0.93; p<.001) but positively associated with the number of non-physician participants (0.12 adjusted bedside minutes per non physician participant; 95% CI 0.07 to 0.17; p = <.001). Education minutes on rounds was positively associated with the presence of an attending physician (2.70 adjusted education minutes; 95% CI 1.27 to 4.12; p<.001) and with one institution (1.39 adjusted education minutes; 95% CI 0.26 to 2.53; p = .02). CONCLUSIONS: Pediatricians spent less time at the bedside on rounds than internal medicine physicians due to reasons other than patient-census or the number of participants in rounds. Compared to historical data, internal medicine rounds were spent more at the bedside engaged in patient care and communication, and less upon educational activities. PMID- 20574535 TI - Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis. AB - Radiotherapy is a widely used treatment option in cancer. However, recent evidence suggests that doses of ionizing radiation (IR) delivered inside the tumor target volume, during fractionated radiotherapy, can promote tumor invasion and metastasis. Furthermore, the tissues that surround the tumor area are also exposed to low doses of IR that are lower than those delivered inside the tumor mass, because external radiotherapy is delivered to the tumor through multiple radiation beams, in order to prevent damage of organs at risk. The biological effects of these low doses of IR on the healthy tissue surrounding the tumor area, and in particular on the vasculature remain largely to be determined. We found that doses of IR lower or equal to 0.8 Gy enhance endothelial cell migration without impinging on cell proliferation or survival. Moreover, we show that low-dose IR induces a rapid phosphorylation of several endothelial cell proteins, including the Vascular Endothelial Growth Factor (VEGF) Receptor-2 and induces VEGF production in hypoxia mimicking conditions. By activating the VEGF Receptor-2, low-dose IR enhances endothelial cell migration and prevents endothelial cell death promoted by an anti-angiogenic drug, bevacizumab. In addition, we observed that low-dose IR accelerates embryonic angiogenic sprouting during zebrafish development and promotes adult angiogenesis during zebrafish fin regeneration and in the murine Matrigel assay. Using murine experimental models of leukemia and orthotopic breast cancer, we show that low-dose IR promotes tumor growth and metastasis and that these effects were prevented by the administration of a VEGF receptor-tyrosine kinase inhibitor immediately before IR exposure. These findings demonstrate a new mechanism to the understanding of the potential pro-metastatic effect of IR and may provide a new rationale basis to the improvement of current radiotherapy protocols. PMID- 20574536 TI - A novel mouse c-fos intronic promoter that responds to CREB and AP-1 is developmentally regulated in vivo. AB - BACKGROUND: The c-fos proto-oncogene is an archetype for rapid and integrative transcriptional activation. Innumerable studies have focused on the canonical promoter, located upstream from the transcriptional start site. However, several regulatory sequences have been found in the first intron. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe an extremely conserved region in c-fos first intron that contains a putative TATA box, and functional TRE and CRE sites. This fragment drives reporter gene activation in fibroblasts, which is enhanced by increasing intracellular calcium and cAMP and by cotransfection of CREB or c Fos/c-Jun expression vectors. We produced transgenic mice expressing a lacZ reporter controlled by the intronic promoter. Lac Z expression of this promoter is restricted to the developing central nervous system (CNS) and the mesenchyme of developing mammary buds in embryos 12.5 days post-conception, and to brain tissue in adults. RT-QPCR analysis of tissue mRNA, including the anlage of the mammary gland and the CNS, confirms the existence of a novel, nested mRNA initiated in the first intron. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a novel, developmentally regulated promoter in the first intron of the c-fos gene. PMID- 20574538 TI - A randomised trial to compare the safety, tolerability and efficacy of three drug combinations for intermittent preventive treatment in children. AB - BACKGROUND: Results from trials of intermittent preventive treatment (IPT) in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP) given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ) and dihydroartemisinin (DHA) plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission. METHODS: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ), SP plus piperaquine (PQ) or dihydroartemisinin (DHA) plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season. RESULTS: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22), 0.06 (95% CI: 0.022, 0.16) and 0.06 (95% CI: 0.02, 0.15) respectively. The incidence of malaria in the control group was 0.79 cases per child year (0.58, 1.08). CONCLUSION: All the three regimens of IPT in children were safe and highly efficacious TRIAL REGISTRATION: ClinicalTrials.gov NCT00561899. PMID- 20574537 TI - Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning. AB - In vertebrate models of synaptic plasticity, signaling via the putative "retrograde messenger" nitric oxide (NO) has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. In the present study, we show that auditory Pavlovian fear conditioning is associated with significant and long-lasting increases in the expression of the postsynaptically-localized protein GluR1 and the presynaptically-localized proteins synaptophysin and synapsin in the lateral amygdala (LA) within 24 hrs following training. Further, we show that rats given intra-LA infusion of either the NR2B-selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibit significant decreases in training-induced expression of GluR1, synaptophysin, and synapsin immunoreactivity in the LA, while those rats infused with the PKG activator 8-Br cGMP exhibit a significant increase in these proteins in the LA. In contrast, rats given intra-LA infusion of the NO scavenger c-PTIO exhibit a significant decrease in synapsin and synaptophysin expression in the LA, but no significant impairment in the expression of GluR1. Finally, we show that intra-LA infusions of the ROCK inhibitor Y-27632 or the CaMKII inhibitor KN-93 impair training induced expression of GluR1, synapsin, and synaptophysin in the LA. These findings suggest that the NO-cGMP-PKG, Rho/ROCK, and CaMKII signaling pathways regulate fear memory consolidation, in part, by promoting both pre- and post synaptic alterations at LA synapses. They further suggest that synaptic plasticity in the LA during auditory fear conditioning promotes alterations at presynaptic sites via NO-driven "retrograde signaling". PMID- 20574539 TI - Increased hepatic insulin action in diet-induced obese mice following inhibition of glucosylceramide synthase. AB - BACKGROUND: Obesity is characterized by the accumulation of fat in the liver and other tissues, leading to insulin resistance. We have previously shown that a specific inhibitor of glucosylceramide synthase, which inhibits the initial step in the synthesis of glycosphingolipids (GSLs), improved glucose metabolism and decreased hepatic steatosis in both ob/ob and diet-induced obese (DIO) mice. Here we have determined in the DIO mouse model the efficacy of a related small molecule compound, Genz-112638, which is currently being evaluated clinically for the treatment of Gaucher disease, a lysosomal storage disorder. METHODOLOGY/PRINCIPAL FINDINGS: DIO mice were treated with the Genz-112638 for 12 to 16 weeks by daily oral gavage. Genz-112638 lowered HbA1c levels and increased glucose tolerance. Whole body adiposity was not affected in normal mice, but decreased in drug-treated obese mice. Drug treatment also significantly lowered liver triglyceride levels and reduced the development of hepatic steatosis. We performed hyperinsulinemic-euglycemic clamps on the DIO mice treated with Genz 112638 and showed that insulin-mediated suppression of hepatic glucose production increased significantly compared to the placebo treated mice, indicating a marked improvement in hepatic insulin sensitivity. CONCLUSIONS/SIGNIFICANCE: These results indicate that GSL inhibition in obese mice primarily results in an increase in insulin action in the liver, and suggests that GSLs may have an important role in hepatic insulin resistance in conditions of obesity. PMID- 20574540 TI - Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment. AB - BACKGROUND: T cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. Subjects with active disease had a greater proportion of polyfunctional cells responding to ESAT-6/CFP-10 stimulation than their infected but non-diseased household contacts (HHC). We therefore wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy. METHODS: We performed a cross-sectional study using PBMC from TB cases (pre- and post-treatment) and HHC. Samples were stimulated overnight with TB antigens (ESAT 6/CFP-10 and PPD) and their CD4+ and CD8+ T cells were assessed for production of CD107a, IFN-gamma, IL-2 and TNF-alpha and the complexity of the responses was determined using SPICE and PESTLE software. RESULTS AND CONCLUSIONS: We found that an increase in complexity (i.e., production of more than 1 factor simultaneously) of the T cell profile was associated with TB disease and that this was significantly reduced following TB treatment. This implies that T cells are able to respond adequately to TB antigens with active disease (at least initially) but the ability of this response to protect the host from disease progression is hampered, presumably due to immune evasion strategies by the bacteria. These findings have implications for the development of new diagnostics and vaccine strategies. PMID- 20574541 TI - Prevention of the recurrence of anaemia in Gambian children following discharge from hospital. AB - BACKGROUND: In malaria endemic countries, children who have experienced an episode of severe anaemia are at increased risk of a recurrence of anaemia. There is a need to find ways of protecting these at risk children from malaria and chemoprevention offers a potential way of achieving this objective. METHODS: During the 2003 and 2004 malaria transmission seasons, 1200 Gambian children with moderate or severe anaemia (Hb concentration <7 g/dL) were randomised to receive either monthly sulfadoxine-pyrimethamine (SP) or placebo until the end of the malaria transmission season in which they were enrolled, in a double-blind trial. All study subjects were treated with oral iron for 28 days and morbidity was monitored through surveillance at health centres. The primary endpoint was the proportion of children with moderate or severe anaemia at the end of the transmission season. Secondary endpoints included the incidence of clinical episodes of malaria during the surveillance period, outpatient attendances, the prevalence of parasitaemia and splenomegaly, nutritional status at the end of the malaria transmission season and compliance with the treatment regimen. RESULTS: The proportions of children with a Hb concentration of <7 g/dL at the end of the malaria transmission season were similar in the two study groups, 14/464 (3.0%) in children who received at least one dose of SP and 16/471 (3.4%) in those who received placebo, prevalence ratio 0.89 (0.44,1.8) P = 0.742. The protective efficacy of SP against episodes of clinical malaria was 53% (95% CI 37%, 65%). Treatment with SP was safe and well tolerated; no serious adverse events related to SP administration were observed. Mortality following discharge from hospital was low among children who received SP or placebo (6 in the SP group and 9 in the placebo group respectively). CONCLUSIONS: Intermittent treatment with SP did not reduce the proportion of previously anaemic children with moderate or severe anaemia at the end of the malaria season, although it prevented malaria. The combination of appropriate antimalarial treatment plus one month of iron supplementation and good access to healthcare during follow-up proved effective in restoring haemoglobin to an acceptable level in the Gambian setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00131716. PMID- 20574542 TI - Nanog variability and pluripotency regulation of embryonic stem cells--insights from a mathematical model analysis. AB - The expression of the transcription factors Oct4, Sox2, and Nanog is commonly associated with pluripotency of mouse embryonic stem (ES) cells. However, recent observations suggest that ES cell populations are heterogeneous with respect to the expression of Nanog and that individual ES cells reversibly change their Nanog expression level. Furthermore, it has been shown that cells exhibiting a low Nanog level are more likely to undergo differentiation. Applying a novel mathematical transcription factor network model we explore mechanisms and feedback regulations to describe the observed variation of the Nanog levels in mouse ES cells. In particular we show that these variations can occur under different assumptions yielding similar experimental characteristics. Based on model predictions we propose experimental strategies to distinguish between these explanations. Concluding from our results we argue that the heterogeneity with respect to the Nanog concentrations is most likely a functional element to control the differentiation propensity of an ES cell population. Furthermore, we provide a conceptual framework that consistently explains Nanog variability and a potential "gate-keeper" function of Nanog expression with respect to the control of ES cell differentiation. PMID- 20574543 TI - Use of Antifungal Combination Therapy: Agents, Order, and Timing. AB - Given the substantial morbidity and mortality related to invasive fungal infections, treatment with a combination of antifungal agents is often considered. A growing body of literature from in vitro studies, animal models, and clinical experience provides data evaluating this approach. This review describes combination antifungal strategies for the management of cryptococcal meningitis, invasive candidiasis, invasive aspergillosis, and rare mold infections. The potential effects that sequencing and timing have on the efficacy of such approaches are discussed, with a focus on recent clinical data in this arena. PMID- 20574544 TI - The Path through Math: Course Sequences and Academic Performance at the Intersection of Race-Ethnicity and Gender. AB - Using new national data from Adolescent Health and Academic Achievement (AHAA), this article examines high school math patterns for students of different race ethnicity and gender. Compared with white males, African American and Latino males receive lower returns from taking Algebra I during their freshman year, reaching lower levels of the math course sequence when they begin in the same position. This pattern is not explained by academic performance, and, furthermore, African American males receive less benefit from high math grades. Lower returns are not observed for minority female students, suggesting that more attention to racial-ethnic inequality in math among male students is needed. PMID- 20574546 TI - Adapting Interpersonal Psychotherapy for Older Adults at Risk for Suicide: Preliminary Findings. AB - We report preliminary findings of the first ever study testing a 16-week course of Interpersonal Psychotherapy (IPT) modified for older outpatients at elevated risk for suicide. Participants were referred from inpatient and outpatient medicine and mental health services. Psychotherapy sessions took place in a therapist's office in a teaching hospital. Twelve adults 60 years or older (M=70.5, SD=6.1) with current thoughts of suicide (suicide ideation) or a wish to die (death ideation) or with recent self-injurious behavior were recruited into weekly sessions of IPT; one was subsequently excluded due to severe cognitive impairment. Participants completed measures of suicide ideation, death ideation, and depressive symptom severity at pre-treatment, mid-treatment, post-treatment, and at 3-month follow-up periods, and measures of therapeutic process variables. Preliminary findings of this uncontrolled pre-post-treatment study support the feasibility of recruiting and retaining older adults at-risk for suicide into psychotherapy research and suggest that adapted IPT is tolerable and safe. Findings indicate a substantial reduction in participant suicide ideation, death ideation, and depressive symptoms; controlled trials are needed to further evaluate these findings. We discuss implications for clinical care with at-risk older adults. PMID- 20574547 TI - On Brownian Distance Covariance and High Dimensional Data. AB - We discuss briefly the very interesting concept of Brownian distance covariance developed by Szekely and Rizzo (2009) and describe two possible extensions. The first extension is for high dimensional data that can be coerced into a Hilbert space, including certain high throughput screening and functional data settings. The second extension involves very simple modifications that may yield increased power in some settings. We commend Szekely and Rizzo for their very interesting work and recognize that this general idea has potential to have a large impact on the way in which statisticians evaluate dependency in data. PMID- 20574545 TI - Biomarkers in Osteosarcoma. AB - Osteosarcoma is the most common primary tumor of bone and accounts for approximately 19% of all malignant tumors of bone. It is the third most common malignant tumor in teenagers. More than twenty years ago, the advent of a multidisciplinary approach that combined multi-agent chemotherapy and limb sparing surgery greatly improved the survival rate of patients with osteosarcoma. Unfortunately, since that time, survival rates have not dramatically improved. To date, the most powerful predictors of outcome have remained the ability to detect metastatic disease at diagnosis and the histopathologic response of the tumor to preoperative chemotherapy. Presently, 80% of patients who do not have distant metastases at initial diagnosis will become long-term survivors. Unfortunately, this means that approximately 20% of patients who do not present with metastases at diagnosis will not survive. This group of patients appears to be resistant to current treatment as attempts to intensify therapy after surgery for patients with a poor histopathologic response has not significantly improved survival rates. It is these patients that are in the greatest need of additional clinically relevant markers for prognosis and who can be most helped by molecular analysis. While steady progress has been made in the identification of genetic alterations in osteosarcoma, no individual molecular marker has thus far been demonstrated to have a better prognostic significance in the treatment of osteosarcomas than the current clinical markers. Thus there is clearly a need to employ new comprehensive analysis technologies to develop significantly more informative classification systems and to identify new therapeutic targets. PMID- 20574548 TI - Changing Structures in Midstream: Learning Along the Statistical Garden Path. AB - Previous studies of auditory statistical learning have typically presented learners with sequential structural information that is uniformly distributed across the entire exposure corpus. Here we present learners with nonuniform distributions of structural information by altering the organization of trisyllabic nonsense words at midstream. When this structural change was unmarked by low-level acoustic cues, or even when cued by a pitch change, only the first of the two structures was learned. However, both structures were learned when there was an explicit cue to the midstream change or when exposure to the second structure was tripled in duration. These results demonstrate that successful extraction of the structure in an auditory statistical learning task reduces the ability to learn subsequent structures, unless the presence of two structures is marked explicitly or the exposure to the second is quite lengthy. The mechanisms by which learners detect and use changes in distributional information to maintain sensitivity to multiple structures are discussed from both behavioral and computational perspectives. PMID- 20574550 TI - Weight Gain After Quitting: Attitudes, Beliefs and Counselling Strategies of Cessation Counsellors. AB - Postcessation weight gain is common and a frequent cause of relapse. Although interventions to address weight gain and weight gain concerns exist, the experience of telephone cessation coun- sellors in addressing weight concerns is unknown. We surveyed 134 cessation counsellors providing quitlines for 30 states regarding their experiences and attitudes about how to address weight gain concerns among smokers trying to quit. Counsellors estimated they discuss weight in 40% of their calls, primarily discussing concerns about gaining weight. Counsellors estimated that smokers gain about 4.1 kg after quitting and about 48% gain more than 2.3 kg. Most counsellors believed that exercise, education about weight gain and preparing smokers for weight gain would help people quit, which is consistent with current science. A total of 51% of counsellors believed that dieting while quitting would reduce weight gain and only 35% correctly identified that dieting reduces a smokers' ability to quit. Some counsellors believed they needed more training in weight management and may need to be reassured that they are currently following treatment guidelines when confronted with smokers who have concerns about postcessation weight gain. PMID- 20574549 TI - Microbubble Compositions, Properties and Biomedical Applications. AB - Over the last decade, there has been significant progress towards the development of microbubbles as theranostics for a wide variety of biomedical applications. The unique ability of microbubbles to respond to ultrasound makes them useful agents for contrast ultrasound imaging, molecular imaging, and targeted drug and gene delivery. The general composition of a microbubble is a gas core stabilized by a shell comprised of proteins, lipids or polymers. Each type of microbubble has its own unique advantages and can be tailored for specialized functions. In this review, different microbubbles compositions and physiochemical properties are discussed in the context of current progress towards developing novel constructs for biomedical applications, with specific emphasis on molecular imaging and targeted drug/gene delivery. PMID- 20574551 TI - Prefrontal Cortex, Emotion, and Approach/Withdrawal Motivation. AB - This article provides a selective review of the literature and current theories regarding the role of prefrontal cortex, along with some other critical brain regions, in emotion and motivation. Seemingly contradictory findings have often appeared in this literature. Research attempting to resolve these contradictions has been the basis of new areas of growth and has led to more sophisticated understandings of emotional and motivational processes as well as neural networks associated with these processes. Progress has, in part, depended on methodological advances that allow for increased resolution in brain imaging. A number of issues are currently in play, among them the role of prefrontal cortex in emotional or motivational processes. This debate fosters research that will likely lead to further refinement of conceptualizations of emotion, motivation, and the neural processes associated with them. PMID- 20574553 TI - The uses and limitations of whole-body magnetic resonance imaging. AB - BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) is a modern imaging method, free of ionizing radiation, which provides high-resolution display of individual organ systems and of the anatomy of the entire body. METHODS: Selective literature review RESULTS: Multi-channel WB-MRI scanners enable both the high-resolution imaging of the entire body and focused studies of individual organs, through the use of various sequence techniques and contrast modes. The initial application of combined cardiovascular and oncological imaging protocols for the screening of asymptomatic persons has already revealed many cases of cardiovascular disease and of tumors with serious clinical implications. The diagnostic accuracy of M staging with WB-MRI lies in the range of 93% to 97%. WB MRI provides good contrast of the bone marrow, and has thus been used for the diagnosis of malignant bone marrow disease as well: in particular, it is especially sensitive for multiple myeloma and plays an important role in prognostication and therapeutic decision-making in this disorder. To date, WB-MRI has not been shown to be superior to other diagnostic techniques with respect to hard endpoints, such as prolongation of survival. It also carries the risk of false positive findings. CONCLUSION: Despite these encouraging results, undirected screening by WB-MRI without an appropriate indication, as is currently being practiced in many institutions, is decidedly inadvisable in view of its predicted diagnostic yield below 2% and the lack of evidence for its cost effectiveness. PMID- 20574552 TI - NMDA Receptors and Colitis: Basic Science and Clinical Implications. AB - During the last decade, research focusing primarily on alterations in the peripheral and central nervous system has improved our understanding of the pathophysiological mechanisms of chronic visceral pain. These studies have demonstrated significant physiological changes following injury to the viscera in the firing patterns of both primary afferent neurons that transmit nociceptive information from the viscera and in central neurons that process the nociceptive information. A number of receptors, neurotransmitters, cytokines, and second messenger systems in these neurons have been implicated in the enhancement of visceral nociception. N-methyl-d-aspartic acid (NMDA) receptors play an important role in chronic visceral pain and hypersensitivity that is present in the setting of colonic inflammation. NMDA receptors are found in the peripheral nervous system as well as the central terminal of primary afferent neurons and have been shown to play an important role in regulating the release of nociceptive neurotransmitters. Recent work has demonstrated the presence of NMDA receptors in the enteric nervous system. In this article, we will discuss more recent evidence of the role of NMDA receptors in visceral pain associated with colitis. PMID- 20574554 TI - Small gifts sustain sales. PMID- 20574557 TI - Resistance tests were not mentioned. PMID- 20574555 TI - A survey of german physicians in private practice about contacts with pharmaceutical sales representatives. AB - BACKGROUND: Physicians and pharmaceutical sales representatives (PSR) are in regular contact. The goal of the present study is systematically to assess the kind of contacts that take place and their quality with a survey of physicians in private practice. A further goal is to determine whether alternatives to current practices can be envisioned. METHODS: 100 physicians in each of three specialties (neurology/psychiatry, general medicine, and cardiology) were surveyed with a questionnaire containing 37 questions. 208 (69.3%) questionnaires were anonymously filled out and returned. RESULTS: 77% (n = 160) of all physicians were visited by PSR at least once a week, and 19% (n = 39) every day. Pharmaceutical samples, items of office stationery and free lunches were the most commonly received gifts. 49% (n = 102) stated that they only occasionally, rarely, or never receive adequate information from PSR, and 76% (n = 158) stated that PSR often or always wanted to influence their prescribing patterns. Only 6% (n = 13) considered themselves to be often or always influenced, while 21% (n = 44) believed this of their colleagues. The physicians generally did not believe that PSR visits and drug company-sponsored educational events delivered objective information, in contrast to medical texts and non-sponsored educational events. Nonetheless, 52% (n = 108) of the physicians would regret the cessation of PSR visits, because PSRs give practical prescribing information, offer support for continuing medical education, and provide pharmaceutical samples. CONCLUSION: PSR visits and attempts to influence physicians' prescribing behavior are a part of everyday life in private medical practice, yet only a few physicians consider themselves to be susceptible to this kind of influence. A more critical attitude among physicians, and the creation of alternative educational events without drug company sponsoring, might lead to more independence and perhaps to more rational and less costly drug-prescribing practices. PMID- 20574558 TI - First-principles study of the ferroelectric and nonlinear optical properties of the LiNbO3-type ZnSnO3. AB - Electronic structures, spontaneous polarization, dynamical and nonlinear optical (NLO) properties of polar oxide ZnSnO(3) with LiNbO(3) (LN)-type structure have been investigated in the framework of density functional theory. By analyzing the Born effectives of LN-type ZnSnO(3), we find that Z* of Zn atoms show relatively large anomalous behavior. The spontaneous polarization is attributed to the large displacement of Zn atoms because of the mixed ionic-covalent character between the Zn-O bonds. The optical dielectric tensor is nearly the same; however the static dielectric tensor shows strongly anisotropy. Furthermore, the nonlinear optical properties are calculated by using 2n + 1 theorem applied to an electric field dependent energy functional. The large dielectric constants and NLO susceptibilities indicate that the LN-type ZnSnO(3) would be a candidate as a high-performance dielectric and nonlinear optical material. PMID- 20574559 TI - A novel and efficient methodology for the construction of quinazolines based on supported copper oxide nanoparticles. AB - A series of quinazolines were synthesized from 2-aminobenzophenones and benzylic amines in good to excellent yields by employing a new heterogeneous catalyst based on the copper oxide nanoparticles supported on kaolin. PMID- 20574560 TI - Enhanced photodegradation of dyes on titania-based photocatalysts by adding commercial GeO2 in aqueous suspension. AB - Adding a small amount of commercial GeO(2) into aqueous suspension significantly enhanced the photocatalytic activity of titania-based photocatalysts for the degradation of dyes. PMID- 20574561 TI - Amido-stabilized rare-earth metal mixed methyl methylidene complexes. AB - Donor(thf)-induced tetramethylaluminate cleavage of Ln(AlMe(4))(2)(NSiMe(3)Ar(iPr)) as well as the reaction of (LnMe(3))(n) (Ln = Y, Ho, Lu) with HNSiMe(3)Ar(iPr) in tetrahydrofuran affords unprecedented trinuclear rare-earth metal tetramethyl methylidene complexes which act as Schrock-type nucleophilic carbenes and methyl transfer agents. PMID- 20574562 TI - Computational and experimental study of the interactions between ionic liquids and volatile organic compounds. AB - Computational chemistry calculations were performed to investigate the interactions of ionic liquids with different classes of volatile organic compounds (VOCs), including alcohols, aldehydes, ketones, alkanes, alkenes, alkynes and aromatic compounds. At least one VOC was studied to represent each class. Initially, 1-butyl-3-methylimindazolium chloride (abbreviated as C(4)mimCl) was used as the test ionic liquid compound. Calculated interaction lengths between atoms in the ionic liquid and the VOC tested as well as thermodynamic data suggest that C(4)mimCl preferentially interacts with alcohols as compared to other classes of volatile organic compounds. The interactions of methanol with different kinds of ionic liquids, specifically 1-butyl-3 methylimidazolium bromine (C(4)mimBr) and 1-butyl-3-methylimidazolium tetrafluoroborate (C(4)mimBF(4)) were also studied. In comparing C(4)mimCl, C(4)mimBr, and C(4)mimBF(4), the computational results suggest that C(4)mimCl is more likely to interact with methanol. Laboratory experiments were performed to provide further evidence for the interaction between C(4)mimCl and different classes of VOCs. Fourier transform infrared spectroscopy was used to probe the ionic liquid surface before and after exposure to the VOCs that were tested. New spectral features were detected after exposure of C(4)mimCl to various alcohols. The new features are characteristic of the alcohols tested. No new IR features were detected after exposure of the C(4)mimCl to the aldehyde, ketone, alkane, alkene, alkyne or aromatic compounds studied. In addition, after exposing the C(4)mimCl to a multi-component mixture of various classes of compounds (including an alcohol), the only new peaks that were detected were characteristic of the alcohol that was tested. These experimental results demonstrated that C(4)mimCl is selective to alcohols, even in complex mixtures. The findings in this work provide information for future gas-phase alcohol sensor design. PMID- 20574563 TI - Biocatalytic preparation and absolute configuration of enantiomerically pure fungistatic anti-2-benzylindane derivatives. Study of the detoxification mechanism by Botrytis cinerea. AB - Enantiomerically pure 2-benzylindane derivatives were prepared using biocatalytic methods and their absolute configuration determined. (1R,2S)-2-Benzylindan-1-ol ((1R,2S)-2) and (S)-2-benzylindan-1-one ((S)-3) were produced by fermenting baker's yeast. Lipase-mediated esterifications and hydrolysis of the corresponding racemic substrates gave rise to the enantiopure compounds (1S,2R)-2 benzylindan-1-ol ((1S,2R)-2) and (1R,2S)-2-benzylindan-1-ol ((1R,2S)-2), respectively. The antifungal activity of these products against two strains of the plant pathogen Botrytis cinerea was tested. The metabolism of anti-(+/-)-2 benzylindan-1-ol (anti-(+/-)-2) by B. cinerea as part of the fungal detoxification mechanism is also described and revealed interesting differences in the genome of both strains. PMID- 20574564 TI - Population distribution of flexible molecules from maximum entropy analysis using different priors as background information: application to the Phi, Psi conformational space of the alpha-(1-->2)-linked mannose disaccharide present in N- and O-linked glycoproteins. AB - The conformational space available to the flexible molecule alpha-D-Manp-(1-->2) alpha-D-Manp-OMe, a model for the alpha-(1-->2)-linked mannose disaccharide in N- or O-linked glycoproteins, is determined using experimental data and molecular simulation combined with a maximum entropy approach that leads to a converged population distribution utilizing different input information. A database survey of the Protein Data Bank where structures having the constituent disaccharide were retrieved resulted in an ensemble with >200 structures. Subsequent filtering removed erroneous structures and gave the database (DB) ensemble having three classes of mannose-containing compounds, viz., N- and O-linked structures, and ligands to proteins. A molecular dynamics (MD) simulation of the disaccharide revealed a two-state equilibrium with a major and a minor conformational state, i.e., the MD ensemble. These two different conformation ensembles of the disaccharide were compared to measured experimental spectroscopic data for the molecule in water solution. However, neither of the two populations were compatible with experimental data from optical rotation, NMR (1)H,(1)H cross relaxation rates as well as homo- and heteronuclear (3)J couplings. The conformational distributions were subsequently used as background information to generate priors that were used in a maximum entropy analysis. The resulting posteriors, i.e., the population distributions after the application of the maximum entropy analysis, still showed notable deviations that were not anticipated based on the prior information. Therefore, reparameterization of homo and heteronuclear Karplus relationships for the glycosidic torsion angles Phi and Psi were carried out in which the importance of electronegative substituents on the coupling pathway was deemed essential resulting in four derived equations, two (3)J(COCC) and two (3)J(COCH) being different for the Phi and Psi torsions, respectively. These Karplus relationships are denoted JCX/SU09. Reapplication of the maximum entropy analysis gave excellent agreement between the MD- and DB posteriors. The information entropies show that the current reparametrization of the Karplus relationships constitutes a significant improvement. The Phi(H) torsion angle of the disaccharide is governed by the exo-anomeric effect and for the dominating conformation Phi(H) = -40 degrees and Psi(H) = 33 degrees. The minor conformational state has a negative Psi(H) torsion angle; the relative populations of the major and the minor states are approximately 3 : 1. It is anticipated that application of the methodology will be useful to flexible molecules ranging from small organic molecules to large biomolecules. PMID- 20574565 TI - BODIPY-functionalized gold nanoparticles as a selective fluoro-chromogenic chemosensor for imaging Cu2+ in living cells. AB - A new fluoro-chromogenic chemosensor based on BODIPY-functionalized gold nanoparticles 1 is prepared. Addition of Cu(2+) ions to aqueous solutions of 1 gave an instantaneous color change along with a blue-shift of the absorption band and quenching of the emission spectrum at room temperature. The chemosensor 1 exhibits a high affinity and selectivity for Cu(2+) over competing metal ions tested. Moreover, confocal microscopy experiments establish that 1 can be used for detecting Cu(2+) levels within living cells. PMID- 20574566 TI - Asymmetric total synthesis of ent-heliespirones A & C. AB - A concise 8-step synthetic route toward ent-heliespirones A & C is described. This synthetic strategy features a highly diastereoselective palladium-catalyzed Michael addition to form 3,5-trans lactone and a final biomimetic intramolecular oxa-spirocyclization. PMID- 20574567 TI - Rational design of efficient rhodium catalysts for the anti-Markovnikov oxidative amination of styrene. AB - Cationic rhodium(I) complexes containing the flexible hemilabile phosphine ligand (3-ethoxypropyl)diphenylphosphine efficiently catalyzed the anti-Markovnikov oxidative amination of styrene in tetrahydrofurane at 80 degrees C to produce (E) 1-styrylpiperidine with turnover frequencies up to 75 h(-1) with excellent enamine selectivity (96%). PMID- 20574568 TI - Introduction of cavities up to 4 nm into a hierarchically-assembled metal-organic framework using an angular, tetratopic ligand. AB - Cavities up to 4 nm have been introduced into a hierarchically-assembled metal organic framework by adopting an angular, semi-flexible tetratopic ligand. The resulting MOF possesses permanent porosity and exhibits stepwise sorption isotherms for O(2) and N(2) gases. PMID- 20574569 TI - Standardized microbial fuel cell anodes of silica-immobilized Shewanella oneidensis. AB - Populations of metabolically active bacteria were associated at an electrode surface via vapor-deposition of silica to facilitate in situ characterization of bacterial physiology and bio-electrocatalytic activity in microbial fuel cells. PMID- 20574570 TI - Bow-tie metallo-cryptophanes from a carboxylate derived cavitand. AB - A new carboxylic acid functionalised cavitand forms [Cu(3)L(2)] metallo cryptophanes with Cu(OAc)(2) that can be linked together into dimers with the bridging ligand 1,2-bis(4-pyridyl)ethylene. Reaction of the cavitand with Co(OAc)(2) gives a metallo-cryptophane with a central Co(7) cluster. PMID- 20574572 TI - Design, synthesis and DNA/RNA binding studies of nucleic acids comprising stereoregular and acyclic polycarbamate backbone: polycarbamate nucleic acids (PCNA). AB - The designed, chiral, acyclic polycarbamate nucleic acids (PCNA) exhibited sequence and orientation specific binding to nucleic acids. Complexes of PCNA with DNA were as stable as PNA:DNA complexes and those with RNA were as stable as natural DNA:RNA complexes. PMID- 20574573 TI - Unusual radical addition on a heteroaromatic nitrogen. A convenient access to new pyrimidine derivatives. AB - A radical generated on the side-chain of a 2- or 4-N-alkylamino-4,6- or 2,6 dichloropyrimidine can cyclise on the nitrogen or on the carbon of the pyrimidine ring depending on its position and on whether an acetyl or a Boc group is present on the extra-nuclear nitrogen. PMID- 20574571 TI - The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building. AB - Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed. PMID- 20574574 TI - A nucleic acid-directed, red light-induced chemical reaction. AB - The first nucleic acid-directed catalytic photochemical reaction that is induced by nontoxic red light was developed. This reaction is fast, high yielding, sequence specific, and enables one to functionalize an oligonucleotide. PMID- 20574575 TI - Investigating metal size effects in the Ln/As/Se/amine (Ln = lanthanide excluding Pm, amine = en, dien, en+trien) systems: solvothermal syntheses and characterizations of lanthanide selenidoarsenates. AB - Three solvothermal systems Ln/As/Se/en, Ln/As/Se/dien and Ln/As/Se/(en+trien) (Ln = lanthanide excluding Pm, en = ethylenediamine, dien = diethylenetriamine, trien = triethylenetetramine) were investigated in detail across the lanthanide series, and ternary lanthanide selenidoarsenates [Ln(en)(3)(H(2)O)(mu-eta(1),eta(1) AsSe(4))] (Ln = La(1a), Ce(1b), Nd(1c)), [Ln(en)(4)]AsSe(4) x 0.5 en (Ln = Sm(1d), Gd(1e), Dy(1f)), [Ln(dien)(2)(mu-eta(1),eta(2)-AsSe(4))] (Ln = La(2a), Ce(2b), Pr(2c)), [Ln(en)(trien)(mu-eta(1),eta(2)-AsSe(4))] (Ln = La(3a), Nd(3b)) and [Sm(en)(trien)(eta(2)-AsSe(4))] (3c) were prepared. Systematic investigations of the three systems clarify the relationship between the molecular structures of the synthetic lanthanide selenidoarsenates and the metal size evolution of the lanthanide series. Meanwhile, the coordination modes of the [AsSe(4)](3-) tetrahedral anion to the same lanthanide ion are dependent on the denticity of ethylene polyamine as the second ligand. The lanthanide selenidoarsenates exhibit semiconducting properties with E(g) between 2.15 and 2.31 eV. PMID- 20574576 TI - High aspect ratio nanoscale multifunctional materials derived from hollow carbon nanofiber by polymer insertion and metal decoration. AB - A novel high aspect ratio material which can simultaneously display multiple functions such as proton and electron conductivity and electrocatalytic activity has been developed by incorporating both platinum nanoparticles and phosphoric acid doped polybenzimidazole along the inner and outer surfaces of a hollow carbon nanofiber. PMID- 20574577 TI - Soil monitoring of pentachlorophenol by bioavailability and ecotoxicity measurements. AB - Several approaches to monitor the bioavailability and ecotoxicity of pentachlorophenol (PCP) in sterile and non sterile soils as a function of aging are reported. Porapak resins and water were used to assess the bioaccessibility and the bioavailability of PCP in soil. Aging effects were observed mainly after 240 d of aging. Actual bioavailability, measured as PCP bioaccumulation in earthworms, decreased more markedly with time. The ecotoxicological biomarker neutral red retention time (NRRT) displayed a dose dependent effect but no aging effects after exposing the earthworms to polluted soils. Nevertheless, mortality of earthworms increased after 240 d at 150 mg kg(-1) contamination. In contrast, the luminescent biosensor Pseudomonas fluorescens pUCD607 evidenced in non sterilized samples a slight reduction of ecotoxicity in time related to the degradation of the molecule. Once again, results highlight the necessity to study the fate of soil pollutants with different chemical and biological approaches. Different PCP degradation pathways and/or the different sensitivity of earthworms and bacteria could explain the different behaviours observed. PMID- 20574578 TI - Room-temperature synthesis of enantioenriched non-protected cyanohydrins using vanadium(salalen) catalyst. AB - Room-temperature synthesis of enantioenriched non-protected cyanohydrins using acetone cyanohydrin as the cyanide source was achieved by V(salalen) catalyst. Aliphatic aldehydes underwent the cyanation with 89-95% ee in the presence of only 0.2-0.4 mol% catalyst. Aromatic cyanohydrins were also obtained in high enantiomeric excesses under modified conditions. PMID- 20574579 TI - Enantioselective synthesis of highly functionalised amides by copper-catalysed vinylogous Mukaiyama aldol reaction. AB - Amides with quaternary stereogenic centers have been synthesised by catalytic asymmetric vinylogous Mukaiyama aldol reactions. The chiral copper-sulfoximine catalyst gives rise to products with moderate to good yields and up to 92% ee. PMID- 20574583 TI - Valence bond all the way: from the degenerate H-exchange to cytochrome P450. AB - This is a personalized Perspective on the development of a valence bond (VB) view of chemical reactivity (J. Am. Chem. Soc., 1981, 103, 3692) as a LEGO process whereby one constructs "reactivity objects", such as barriers, transition states, and reaction intermediates from VB building blocks, and thereby understands and predicts chemical reactivity in a unified manner. In so doing, I have tried to give the reader a panoramic set of applications, from the simple H-exchange reaction all the way to alkane hydroxylation by cytochrome P450 (Prog. Phys. Org. Chem. 1985, 15, 197; Angew. Chem., Int. Ed., 1999, 38, 586). PMID- 20574584 TI - A small molecule that mimics the metabolic activity of copper-containing amine oxidases (CuAOs) toward physiological mono- and polyamines. AB - Primary aliphatic biogenic amines have been successfully oxidized using a quinonoid species that mimics the metabolic activity of copper-containing amine oxidase (CuAO) enzymes. Especially, high catalytic performances were observed with aminoacetone, a threonine catabolite, and methylamine, a metabolite of adrenaline, and with the primary amino groups of putrescine and spermidine which are both decarboxylation products of ornithine and S-adenosyl-methionine. Furthermore, contrary to flavine adenine dinucleotide (FAD)-dependent amine oxidase enzymes, no activity was found toward secondary and tertiary amines. PMID- 20574585 TI - Calcium binding environments probed by (43)Ca NMR spectroscopy. AB - Calcium is an important component of materials, metalloproteins, minerals, glasses, and small inorganic and organic complexes. However, NMR spectroscopy of the quadrupolar (43)Ca nuclide remains difficult primarily due to its low natural abundance and low resonance frequency. In this Perspective, experimental challenges and recent successes in the field are highlighted, with a focus on solid-state (43)Ca NMR spectroscopy. Solution (43)Ca NMR studies of calcium binding biomolecules are also presented. The structural insights afforded from quadrupolar and chemical shift parameters are examined. For example: isotropic chemical shifts have been shown to correlate with the mean Ca-O distance and also with calcium coordination number; quadrupolar coupling constants and chemical shift tensor spans have been shown to be useful probes of polymorphism; and, distance measurements involving (43)Ca have been recently demonstrated. Lastly, challenges and opportunities for the future are considered. PMID- 20574586 TI - Towards molecular diversity: dealkylation of tert-butyl amine in Ugi-type multicomponent reaction product establishes tert-butyl isocyanide as a useful convertible isonitrile. AB - With the development of a novel microwave-assisted one-pot tandem de-tert butylation of tert-butyl amine in an Ugi-type multicomponent reaction product, tert-butyl isocyanide as a useful convertible isonitrile has been explored for the first time affording access to molecular diversity of pharmaceutically important polycyclic N-fused imidazo-heterocycles. PMID- 20574587 TI - Fourier transform mass spectrometry for metabolome analysis. AB - The metabolome is characterized by a large number of molecules exhibiting a high diversity of chemical structures and abundances, requiring complementary analytical platforms for extensive coverage. Of these analytical platforms, atmospheric pressure ionization Fourier transform mass spectrometry (FT/MS) instruments are popular because they provide accurate mass measurements with ppm and even sub-ppm errors, and also high and ultra-high resolving power. In this article, we evaluate the improvements provided for metabolomics by different types of FT/MS instruments, together with the ability of these platforms to cover the various analytical requirements: global metabolite profiling, absolute quantification and also structural characterization, of metabolomics. The specificities of FT/MS in terms of data pre-processing and the input of accurate mass measurements for biological interpretation and for highlighting metabolic networks are also addressed. PMID- 20574588 TI - A kinetic study of the decomposition of the cubic perovskite-type oxide Ba(x)Sr(1 x)Co(0.8)Fe(0.2)O(3-delta) (BSCF) (x = 0.1 and 0.5). AB - The decomposition of the cubic perovskite-type oxide Ba(x)Sr(1 x)Co(0.8)Fe(0.2)O(3-delta) (BSCF) into hexagonal and cubic perovskite-type phases has been examined by means of Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED) and X-Ray Diffraction (XRD). SEM and TEM measurements reveal that the new hexagonal phase grows predominantly at the grain boundaries of BSCF ceramics and that the cation composition of the newly formed hexagonal phase differs from that of the starting material. An orientational relationship between the hexagonal and the parent cubic phase was also observed. By means of ex situ XRD the phase fraction of the hexagonal phase was determined as a function of annealing time. A kinetic analysis of the data, based on Avrami-type kinetics, indicates that the decomposition is independent of the initial A-site composition, and the obtained reaction order supports the conclusion that the hexagonal phase grows at the grain boundaries in dense ceramic samples. PMID- 20574589 TI - NIR-laser-induced selective rotamerization of hydroxy conformers of cytosine. AB - The relative populations of two amino-hydroxy conformers of cytosine, differing in rotation of the OH group by approximately 180 degrees , were selectively and repeatedly manipulated with narrowband, near-infrared laser light. For cytosine monomers isolated in a low-temperature Ar matrix, laser irradiations at 7013 cm( 1) and at 7034 cm(-1) were found to induce effective transformations of the two conformers into each other. PMID- 20574590 TI - Functional magnetic nanoparticle-based label free fluorescence detection of phosphorylated species. AB - A label free fluorescence method for rapid detection of the presence of phosphorylated peptides/proteins in sample solutions using functional magnetic nanoparticles (MNPs) as the detection probes is demonstrated. PMID- 20574591 TI - Chemoenzymatic synthesis of glycosylphosphatidylinositol-anchored glycopeptides. AB - MUC1 glycopeptide was efficiently coupled to glycosylphosphatidylinositol (GPI) derivatives by sortase A (SrtA), verifying that SrtA can accept sterically hindered glycopeptide as substrate for ligation with GPIs. This work has established a practical method for the chemoenzymatic synthesis of GPI-linked glycopeptides. PMID- 20574592 TI - Self-assembly of hydrogen-bonded chains of molecular landers. AB - One-dimensional chains of a specially designed lander molecule with di-carboxyl imide functional moieties, enabling complementary intermolecular hydrogen bonding, have been self-assembled under ultra high vacuum conditions on a Au(111) surface and characterized by scanning tunneling microscopy. PMID- 20574593 TI - Interfacial Cu/ZnO contact by selective photodeposition of copper onto the surface of small ZnO nanoparticles in non-aqueous colloidal solution. AB - Nanoscale copper was selectively photodeposited onto the surface of hexadecylamine (HDA) stabilized (monodispersed not agglomerated) ZnO nanoparticles (NPs) of a diameter of 2-5 nm, which leads to HDA-stabilized Cu/ZnO NPs of varied Cu loading. The particles are soluble in non-polar organic solvents. The line broadening and the red shift of the surface plasmon band of Cu/ZnO NPs relative to HDA-stabilized Cu NPs, the profound decrease of the Cu/ZnO NPs visible photoluminescence at 525 nm, the increase of the UV emission intensity at 365 nm and the enhancement of the Raman scattering (RS) intensity in comparison to the parent ZnO NPs confirmed the interfacial contact between the Cu and ZnO phase. PMID- 20574594 TI - Oxidative addition across Zr/Co multiple bonds in early/late heterobimetallic complexes. AB - The reactivity of heterobimetallic Zr/Co complexes linked by phosphinoamide ligands towards the oxidative addition of I(2) and alkyl halides is reported. These reactions are accompanied by dissociation of one phosphine ligand from Co and eta(2)-coordination to Zr. Addition of H(2) leads to both oxidative addition across the M-M bond and P-N bond cleavage. PMID- 20574595 TI - In this issue: to expose or not to expose? PMID- 20574597 TI - Systemic combination treatment for psoriasis: a review. AB - Psoriasis is a chronic inflammatory skin disease, which affects approximately 2.6% of the population in Northern Europe and Scandinavia. In order to achieve disease control, combinations of systemic treatments are sometimes needed for variable time periods. However, no evidence-based guidelines exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination treatments. The most thoroughly investigated combination was retinoid and phototherapy. Further controlled research is needed to define the safest and most effective combination regimens. PMID- 20574598 TI - Ceramides and barrier function in healthy skin. AB - Lipids in the stratum corneum are key components in the barrier function of the skin. Changes in lipid composition related to eczematous diseases are well known, but limited data are available on variations within healthy skin. The objective of the present study was to compare ceramide subgroups and ceramide/cholesterol ratios in young, old, male and female healthy skin. A total of 55 participants with healthy skin was included in the study. Lipid profiles were correlated with transepidermal water loss and with information on dry skin from a questionnaire including 16 people. No statistically significant differences were found between young and old skin for ceramide subgroups or ceramide/cholesterol ratios, and there was no statistically significant correlation between answers about dry skin and ceramide levels. Interestingly, a statistically significant higher ceramide/cholesterol ratio was found for men than for women (p = 0.02). PMID- 20574599 TI - Effect of itch, scratching and mental stress on autonomic nervous system function in atopic dermatitis. AB - Atopic dermatitis is a stress-responsive disorder that involves the autonomic nervous system. The current study used heart rate variability to examine the effect of itch, scratching and mental stress in atopic patients with moderate to severe disease. Twenty-one patients with active disease and 24 healthy volunteers participated in the study. Heart rate variability measurements were taken at 5 min intervals at rest and after each of 3 acute stress tests, which included histamine-induced itch at the forearm, scratching around the itch site, and the Trier Social Stress Test. Atopic patients displayed a higher heart rate than healthy controls in all 4 experimental settings, which was statistically significant using Cohen's delta analysis. The very low frequency component of the power spectrum, indicative of sympathetic activity, showed a 200% increase after scratching in patients with atopic dermatitis. The high frequency component, reflecting parasympathetic tone, responded swiftly to itch and scratching in healthy controls, but displayed a limited adaptability in atopic dermatitis. This study supports the concept that atopic dermatitis is a stress-responsive disorder and involves autonomic nervous system dysfunction. Atopic subjects exhibited an overactive sympathetic response to itch and scratching, while the parasympathetic tone was persistently and rigidly elevated, showing a lack of adaptability in response to stress. PMID- 20574600 TI - Non-melanoma skin cancer and ten-year all-cause mortality: a population-based cohort study. AB - Confounding from comorbidity and socioeconomic status may have biased earlier findings of all-cause mortality among patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We therefore examined all-cause mortality among 72,295 Danish patients with BCC, 11,601 with SCC, and 383,714 age- and gender-matched population control cohort subjects with extensive control for comorbidity and socioeconomic status. Data on cancer, death, and socioeconomic status were obtained from medical databases and Statistics Denmark. We analysed data using Cox regression analysis, with estimation of 10-year mortality rate ratios (MRRs) and 95% confidence intervals (CI). Mortality was reduced among patients with BCC (10-year MRR = 0.91 (95% CI: 0.89-0.92) and did not vary by age, comorbidity, or socioeconomic status. Mortality among patients with SCC was increased and varied by age, selected chronic diseases, but not socioeconomic status. The reduced mortality observed among patients with BCC and the increased mortality among patients with SCC persisted even after extensive control for comorbidity and socioeconomic status. PMID- 20574601 TI - Variation in epidermal morphology in human skin at different body sites as measured by reflectance confocal microscopy. AB - Two methods of estimating stratum corneum thickness using reflectance confocal microscopy were examined, and epidermal thickness measurements at multiple body sites were compared. Measurements of stratum corneum thickness were made using the derivative method, which is based on the rate of change of image intensity as a proxy for keratin concentration, and simple visual analysis of confocal images. To compare epidermal thickness we collected 1491 z-axis stacks of confocal images from 10 body sites in 39 subjects. An artefact associated with the imaging process interfered with the derivative method for stratum corneum thickness, and simple visual analysis is to be preferred. Although some epidermal properties varied by site, the most striking finding was the degree of within-site variation, which accounted for between 50% and 74% of the total variation observed. The majority of this variation was not due to measurement error, and represents genuine topographical irregularity. This fine-scale variation limits the ease of use of reflectance confocal microscopy for quantitative studies of the epidermis and stratum corneum. PMID- 20574602 TI - Ethosome formulations of known contact allergens can increase their sensitizing capacity. AB - Vesicular systems, such as liposomes and ethosomes, are used in cosmetic and pharmaceutical products to encapsulate ingredients, to protect ingredients from degradation, to increase bioavailability, and to improve cosmetic performance. Some reports have suggested that formulation of cosmetic ingredients in vesicular carrier systems may increase their contact allergy elicitation potential in humans. However, no sensitization studies have been published. We formulated two model contact allergens (isoeugenol and dinitrochlorobenzene) in ethosomes and investigated the sensitization response using a modified local lymph node assay (LLNA). The results were compared with those for the same allergens in similar concentrations and vehicles without ethosomes. Both allergens encapsulated in 200 300 nm ethosomes showed increased sensitizing potency in the murine assay compared with the allergens in solution without ethosomes. Empty ethosomes were non-sensitizing according to LLNA. The clinical implications are so far uncertain, but increased allergenicity from ethosome-encapsulated topical product ingredients cannot be excluded. PMID- 20574603 TI - Differences in the peritumoural inflammatory skin infiltrate between squamous cell carcinomas in organ transplant recipients and immunocompetent patients. AB - Organ transplant recipients (OTR) have a greatly increased risk (up to 100 times) of developing squamous cell carcinomas (SCC) in the skin. This is attributed specifically to chronic immunosuppression, causing dysfunctional viral defence and tumour protection. To investigate the possible link between increasing risk of SCCs and type of inflammation in these tumour-prone patients, we analysed the peritumoural infiltrates with regard to cell types and densities. Seven SCCs from immunosuppressed OTR and 14 SCCs from immunocompetent patients were immun histochemically stained for CD3, CD4, CD8, CD56, CD20, CD138, CD14, CD68, CD1a. Cell counts were performed with the aid of computer-based image analysis of > 100,000 cells. When comparing the percentage distributions, significant differences were detected (outlined as median values (min-max)): T cells (CD3+): OTR 57% (35-78), controls 68% (48-80), p = 0.036; plasma cells (CD138+): OTR 2% (0.7-7), controls 0.2% (0-1.2), p = 0.001; mono-cytes (CD14+): OTR 3.2% (1.1 5.6), controls 9.3% (2.2-17.2), p = 0.014. Surprisingly, no differences in cell densities, i.e. cells/mm2 tumour section area, were detected between the 2 groups. In conclusion, we found that the peritumoural infiltrates in immunosuppressed compared with immunocompetent patients differ in cellular composition, inferring a more tumour-submissive environment in OTR. However, cellular densities were equal, suggesting deviating cellular functionality in OTR. PMID- 20574604 TI - A database analysis of cutaneous lupus erythematosus with the EUSCLE Core Set Questionnaire. AB - The aim of this study was to determine whether the Core Set Questionnaire developed recently by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) is a useful tool to evaluate clinical features and therapeutic strategies in cutaneous lupus erythematosus. Disease characteristics were analysed in 50 patients with different subtypes of cutaneous lupus erythematosus from two European centres (Germany and Sweden). Mean age at onset of disease was 42.0 +/- 13.3 years (range: 7-69 years) and this differed significantly between the cutaneous lupus erythematosus subtypes. Moreover, 22 (44.0%) of the patients with cutaneous lupus erythematosus fulfilled four or more of the American College of Rheumatology (ACR) criteria; however, only 7 (14.0%) had severe systemic organ manifestations, such as kidney involvement. The analysis of serological features, such as antinuclear antibodies, revealed further significant differences between the cutaneous lupus erythematosus subtypes. In conclusion, the EUSCLE Core Set Questionnaire provides a useful tool for standardized collection and statistical analysis of data on cutaneous lupus erythematosus in clinical practice. PMID- 20574605 TI - Somatic and psychiatric comorbidity in patients with chronic pruritus. AB - It has been reported that 10-50% of patients with pruritus but no skin rash have an underlying systemic disease and up to 70% a psychiatric one. The aim of this retrospective study was to review the records of a large number of patients with chronic pruritus for concomitant diseases and treatment options. Medical records of 139 patients (52 males, 87 females) with chronic pruritus who visited the outpatient dermatological clinic during a 17-month period were reviewed. Itch was the presenting symptom in 6 of 47 patients with systemic disease and in 17 of 31 patients with psychiatric disease. Twenty-four patients had neuropathic itch and 37 patients had pruritus of unknown origin. The most severe and long-lasting itch was found in patients with multiple systemic diseases and in those with pruritus of unknown origin. Pruritus of the scalp and face was most common in psychogenic pruritus. Phototherapy was found to be a useful therapeutic option. In conclusion, systemic diseases are unlikely to cause chronic pruritus in patients consulting a dermatology department. PMID- 20574606 TI - Correlation of immunological profile with phenotype and disease outcome in pemphigus. AB - There has been no previous clinical-immunological study of pemphigus in Spain. The aim of this study was to perform a retrospective analysis of pemphigus patients who had been followed for a period of 18 years in our centre. We characterized the autoantibody response, compared diagnostic assays and correlated the immunobiological data with phenotype and prognosis. Clinical, epidemiological and immunopathological data were collected from 40 patients. Patients sera were characterized by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Epidemiological and clinical findings were comparable to other series. Mortality during follow-up was 0% and 6% in pemphigus foliaceus and vulgaris, respectively. Importantly, higher indirect immunofluorescence titres and anti-desmoglein 3 ELISA values of samples from untreated patients correlated significantly with a potentially worse clinical course. Moreover, there was a positive correlation between indirect immunofluorescence titres and anti-desmoglein 3 ELISA levels in pemphigus vulgaris patients. Based on our findings, initial high anti-desmoglein 3 antibodies in pemphigus patients correlate with a more adverse prognosis, which raises the question as to whether a more aggressive initial therapy is indicated in patients with this immunological pattern. PMID- 20574607 TI - Ultrastructural demonstration of a relationship between acquired cutis laxa and monoclonal gammopathy. AB - Acquired cutis laxa is an uncommon disorder sometimes associated with monoclonal gammopathy and multiple myeloma, although the mechanism of this link is unclear. We report here a case of a 34-year-old man with generalized acquired cutis laxa and monoclonal light chain disease with renal and neurological involvement. Electron microscopy examination of a skin sample revealed shortened and fragmented elastic fibres in the reticular dermis and normal collagen bundles. Immunogold labelling revealed anti-lambda antibodies closely bound to the microfibrillar component of elastic fibres, thus supporting a causal relationship between monoclonal gammopathy and the changes in skin elasticity. PMID- 20574608 TI - Treatment of extrafacial rosacea with low-dose isotretinoin. PMID- 20574609 TI - Simvastatin in psoriasis: ambiguous effects. PMID- 20574610 TI - Dermochondrocorneal dystrophy (Francois' syndrome). PMID- 20574612 TI - Solitary glomus tumour on the nostril of a child: unusual clinical presentation. PMID- 20574611 TI - Aspirin-intolerant chronic urticaria exacerbated by cutaneous application of a ketoprofen poultice. PMID- 20574613 TI - Imiquimod for the treatment of classical Kaposi's sarcoma. PMID- 20574615 TI - A case of primary idiopathic cutaneous pustular vasculitis. PMID- 20574614 TI - Cutaneous lymphoid hyperplasia associated with Leishmania panamensis infection. PMID- 20574616 TI - Leukaemia cutis at the site of striae distensae: an isotopic response? PMID- 20574617 TI - Painful Buruli ulcer in a Malian visitor to France. PMID- 20574618 TI - Refractory chronic urticaria treated effectively with the protease inhibitors, nafamostat mesilate and camostat mesilate. PMID- 20574619 TI - Bullous amyloidosis mimicking bullous pemphigoid: usefulness of electron microscopic examination. PMID- 20574620 TI - Possible acceleration of regression by antibiotic treatment in benign cephalic histiocytosis with infiltration of CD11a/CD11c+ macrophages. PMID- 20574621 TI - Necrotizing soft tissue infection of the glans penis due to atypical Candida species complicated with Fournier's gangrene. PMID- 20574622 TI - Skin necrosis revealing antiphospholipid syndrome during immunotherapy for melanoma. PMID- 20574623 TI - Trichoblastoma-like tumour with follicular, matrical and sebaceous differentiation: involvement of hair follicle stem cells? PMID- 20574624 TI - CK7+/CK20- Merkel cell carcinoma presenting as inguinal subcutaneous nodules with subsequent epidermotropic metastasis. PMID- 20574625 TI - Diagnostic pitfalls of using dermoscopic features to differentiate between malignant melanoma and pigmented seborrhoeic keratosis. PMID- 20574626 TI - Procalcitonin as a biomarker for toxic shock syndrome. PMID- 20574627 TI - Two cases of severe refractory chronic idiopathic urticaria treated with omalizumab. PMID- 20574628 TI - Cystic nodules affecting sexual activity: a quiz. Steatocystoma multiplex. PMID- 20574629 TI - White papules around the ears: a quiz. Milia en plaque. PMID- 20574630 TI - Comparison of a new whole-body continuous-table-movement protocol versus a standard whole-body MR protocol for the assessment of multiple myeloma. AB - OBJECTIVES: To evaluate a whole body (WB) continuous-table-movement (CTM) MR protocol for the assessment of multiple myeloma (MM) in comparison to a step-by step WB protocol. METHODS: Eighteen patients with MM were examined at 1.5T using a WB CTM protocol (axial T2-w fs BLADE, T1-w GRE sequence) and a step-by-step WB protocol including coronal/sagittal T1-w SE and STIR sequences as reference. Protocol time was assessed. Image quality, artefacts, liver/spleen assessability, and the ability to depict bone marrow lesions less than or greater than 1 cm as well as diffuse infiltration and soft tissue lesions were rated. Potential changes in the Durie and Salmon Plus stage and the detectability of complications were assessed. RESULTS: Mean protocol time was 6:38 min (CTM) compared to 24:32 min (standard). Image quality was comparable. Artefacts were more prominent using the CTM protocol (P = 0.0039). Organ assessability was better using the CTM protocol (P < 0.001). Depiction of bone marrow and soft tissue lesions was identical without a staging shift. Vertebral fractures were not detected using the CTM protocol. CONCLUSIONS: The new protocol allows a higher patient throughput and facilitates the depiction of extramedullary lesions. However, as long as vertebral fractures are not detectable, the protocol cannot be safely used for clinical routine without the acquisition of an additional sagittal sequence. PMID- 20574631 TI - The culprit lesion and its consequences: combined visualization of the coronary arteries and delayed myocardial enhancement in dual-source CT: a pilot study. AB - OBJECTIVE: To assess combined analysis of coronary arteries and delayed myocardial contrast enhancement based on co-registration of coronary CT angiography and late-phase CT and automatic segmentation. MATERIALS AND METHODS: Co-registration and late enhancement segmentation were applied to coronary CT angiography and late-phase CT images from six pigs with acute myocardial infarction (MI) and six patients with chronic MI. MI size was quantified by manual delineation, the established 3SD method, and a new mixture model approach. Correspondence between coronary artery lesions and MI was assessed visually from fused segmentation results. RESULTS: Co-registration was successful in all cases. There was substantial agreement in the number of segments diagnosed with MI, comparing manual delineation and the mixture model for animal (kappa = 0.839) and patient studies (kappa = 0.770). There were no significant differences between the two methods (P > 0.05). In patients there was a discrepancy between the segmental distribution of MI and empirical coronary artery perfusion in 10/96 segments when compared with the true coronary branching pattern. CONCLUSION: The mixture model approach is well suited for automated assessment of MI size from late-phase cardiac CT. Fusion imaging eliminates the need for empirical knowledge of the anatomical relationship between the coronary artery lesion and the area of myocardial ischaemia. PMID- 20574632 TI - Longitudinal study of a mouse model of chronic pulmonary inflammation using breath hold gated micro-CT. AB - OBJECTIVES: To evaluate the feasibility of using automatic quantitative analysis of breath hold gated micro-CT images to detect and monitor disease in a mouse model of chronic pulmonary inflammation, and to compare image-based measurements with pulmonary function tests and histomorphometry. MATERIAL AND METHODS: Forty nine A/J mice were used, divided into control and inflammation groups. Chronic inflammation was induced by silica aspiration. Fourteen animals were imaged at baseline, and 4, 14, and 34 weeks after silica aspiration, using micro-CT synchronized with ventilator-induced breath holds. Lung input impedance was measured as well using forced oscillation techniques. Five additional animals from each group were killed after micro-CT for comparison with histomorphometry. RESULTS: At all time points, micro-CT measurements show statistically significant differences between the two groups, while first differences in functional test parameters appear at 14 weeks. Micro-CT measurements correlate well with histomorphometry and discriminate diseased and healthy groups better than functional tests. CONCLUSION: Longitudinal studies using breath hold gated micro CT are feasible on the silica-induced model of chronic pulmonary inflammation, and automatic measurements from micro-CT images correlate well with histomorphometry, being more sensitive than functional tests to detect lung damage in this model. PMID- 20574633 TI - Embolization of pulmonary arteriovenous malformations using the Amplatzer vascular plug: successful treatment of 69 consecutive patients. AB - OBJECTIVE: The technique of embolization of pulmonary arteriovenous malformations (PAVMs) with the Amplatzer vascular plug (AVP) has been reported, but no large series has evaluated the effectiveness of this relatively new embolic device. The purpose of this study is to assess the role of AVPs in the treatment of PAVMs. MATERIALS AND METHODS: Sixty-nine consecutive patients underwent embolization of pulmonary arteriovenous malformations between September 2006 and December 2008. Clinical, procedural, and physiological data were reviewed retrospectively. RESULTS: Of 161 PAVMs, 120 (75%) were successfully embolized with Amplatzer vascular plugs alone. Complete and rapid occlusion of feeding vessels was easily achieved at the site of arteriovenous communication without complication. Particularly small or tortuous feeding arteries supplying 27 complex and 14 simple PAVMs were occluded with coils. There have been no documented instances of recanalization on follow-up. CONCLUSION: Amplatzer vascular plugs allow the rapid and safe distal occlusion of the majority of PAVMs. PMID- 20574634 TI - Alcohol and sexual risk behavior among migrant female sex workers and male workers in districts with high in-migration from four high HIV prevalence states in India. AB - This paper examines the association between alcohol use and sexual risk in two critical migrant populations living within the same geographical areas--migrant men and female sex-workers (FSWs). Data are drawn from two independent surveys of migrant FSWs and male workers in 14 districts of four high HIV prevalent Indian states. In the paper we have examined the independent effects of degree of mobility and alcohol use prior to sex on HIV risk behaviors. Nearly two-thirds of FSWs and a similar proportion of male migrant workers, as well as nine out of ten clients of FSWs consume alcohol. More than half of the FSWs and their clients consumed alcohol prior to sex. The practice of alcohol use prior to sex among both FSWs and their clients has a significant association with inconsistent condom use during paid as well as unpaid sex, and these effects are independent of degree of mobility. The results suggest a need for developing an in-depth understanding of the role of alcohol in accentuating HIV risk particularly among migrant populations who move frequently from one place another. PMID- 20574635 TI - Ethnographic mapping of alcohol use and risk behaviors in Delhi. AB - This paper examines mapping and related data-gathering at geographical locations of vulnerable urban groups with regard to risky sexual behaviors and alcohol/drug use in the capital city of Delhi. The aim is to describe the situations of special geographic locations and sub-groups in relation to alcohol/drug use and risks of HIV/STI infections. The study was part of a community program for alcohol and drug users in slum communities in West and East Delhi carried out by the National Drug Dependence Treatment Centre (NDDTC) of the All India Institute of Medical Science (AIIMS), New Delhi, India. As part of a WHO multi-centered qualitative study among selected groups, mapping was done at different sites concerning alcohol use, social contexts, involvement in sexual risk behavior, availability of sex partners and related factors. Easy access to alcohol and drugs, accompanied by availability of sex workers appeared as compound risk factors in the study sites. Reported risky sexual behaviors included nonuse or irregular use of condoms, multiple sex partners, group sex, and anal sex with hijras (eunuchs). PMID- 20574636 TI - Feasibility and effectiveness of HIV prevention among wives of heavy drinkers in Bangalore, India. AB - Few studies have examined the effectiveness of community based HIV interventions for monogamous married women. We examined prevalence of risky behaviors and effectiveness of a Western intervention on increased knowledge and reductions in risky behaviors among wives of heavy drinkers in an urban slum in Bangalore, India. Household enumeration was conducted on 509 households; wives of the youngest married man 18-50 years of age who scored 8+ on the Alcohol Use Disorder Identification Test (AUDIT) were selected (N = 100) and assessed with Indian adaptations of the Substance Abuse Module (SAM), the Washington University Risk Behavior Assessment for Women (WU-RBA-W), the Violence Exposure Questionnaire (VEQ), the CES-D, the Diagnostic Interview Schedule (DIS-IV), and a Proxy AUDIT. After random assignment to either the Standard (Pre-post HIV counseling; N = 50) or the Enhanced Intervention (Standard + Body Wise Intervention; N = 50), women were re-assessed at 2 months; a 100% follow-up rate was achieved. Though no major intervention effects were found, at follow-up women were less likely to report victimization and perpetrated violence, more likely to feel empowered to make decisions about birth control, and were more knowledgeable about how to protect themselves from STDs and HIV. The findings have implications for HIV prevention among at risk monogamous women in community settings. PMID- 20574637 TI - Alcohol use, sexual risk behavior and STIs among married men in Mumbai, India. AB - This paper examines the relationship of frequency, type of alcohol use, sexual risk behaviors and sexually transmitted infections (STIs) among married men living in economically marginal communities in Mumbai, India. The findings indicate that men who consume alcohol daily were four times more likely to have had extramarital sex in the past 12 months. In terms of sexually transmitted infections, men who were daily drinkers were four times more likely than those not consuming alcohol in the last month to have gonorrhea (NG) and Chlamydia (CT) infection and three times more likely to have had a past history of exposure to herpes simplex virus-2 (HSV-2) and/or syphilis as determined by biological testing. These results demonstrate that men with daily alcohol use are at greatest risk for STIs and need to be targeted for community outreach, de addiction services and sex risk reduction education program in India and elsewhere. PMID- 20574638 TI - Oral disease-modifying therapies for multiple sclerosis: are we there yet? PMID- 20574639 TI - Fatal acute pancreatitis occurring outside of the hospital: clinical and social characteristics. AB - BACKGROUND: Mortality caused by acute pancreatitis in patients admitted to the hospital has been thoroughly investigated, but knowledge regarding outpatient fatalities is far from complete. The purpose of this study was to assess the incidence and clinical characteristics of patients who have died due to acute pancreatitis occurring outside the hospital. METHODS: Deaths caused by acute pancreatitis in the southern part of Sweden during 1994-2008 were identified at the Department of Forensic Medicine, Lund. A retrospective review of all cases was performed. RESULTS: A total of 50 patients were included, representing approximately 50 of 292 (17%) of all deaths due to acute pancreatitis in the region during this period of time. Median age was 54 (47-69) years and the majority-37 (74%)-were men. The main etiology was alcohol, seen in at least 35 (70%) patients. Twelve (24%) patients were obese. The duration of abdominal pain, in evaluable cases, was 3.0 (1.6-6.2) days. Profound signs of pancreatitis were seen in all patients; 35 (70%) had a necrotising disease according to histopathological examination. Pulmonary changes were common, e.g., bronchopneumonia, pleural effusion, or edema, and all but four had fatty liver. Massive intra-abdominal bleeding was seen in one patient. At least eight patients had a mental disorder, and three were homeless. CONCLUSIONS: Fatal acute pancreatitis occurring outside the hospital accounts for a substantial part of all deaths due to the disease. The incidence seems to decline, and no variation in season was seen. Alcohol was the predominant etiology. Many of the patients lived alone and in poor social conditions. PMID- 20574640 TI - The impending severe shortage of trauma/critical care surgeons in the USA. PMID- 20574641 TI - Analysis of two VP60 capsid protein genes of rabbit hemorrhagic disease virus from viruses obtained from the same farm. AB - Two distinct clones of the VP60 capsid protein gene of rabbit hemorrhagic disease virus were amplified from mixed liver tissue of rabbits collected from the same farm in the Xinjiang Uygur Autonomous Region of China in 2002. The results of DNA sequence analysis showed that the length of the VP60 gene in the first clone was 1,740 bp, similar to other VP60 genes. The length of the VP60 gene in the second clone was only 1,536 bp. The two clones were predicted to encode 579 and 511 amino acids, respectively. PMID- 20574642 TI - Evidence for recombination between vaccine and wild-type mumps virus strains. AB - Recombination of mumps virus (MuV) has rarely been reported. In this study, phylogenetic and recombination analyses were performed on 30 complete MuV genomes, including 17 vaccine and 13 wild-type strains. One potentially significant recombination event was found to have occurred between the lineage represented by the vaccine strain L3/Russia/Vector (AY508995) as the minor parent and wild MuV strain Drag94 (AY669145) as the major parent, and this led to a recombinant, 9218/Zg98 (EU370206), a wild-type MuV strain isolated from a 3-year old boy with parotitis. In summary, we found a recombinant of MuV derived from vaccine and wild-type MuV strains. PMID- 20574643 TI - Naturally occurring recombination between distant strains of infectious bronchitis virus. AB - New variants of infectious bronchitis virus (IBV) have emerged in Australia despite its geographical isolation and intensive vaccination programs. In the present study, the 3' terminal 7.2 kb of the genome of a recently isolated variant of IBV (N1/03) was sequenced and compared with the sequences of classical and novel strains of IBV, the two main groups of these viruses in Australia. The comparison revealed that recombination between classical and novel IBVs was responsible for the emergence of the new variant. It was concluded that novel IBVs, which have not been detected since 1993, and which are phylogenically more distant from classical IBVs than turkey coronaviruses, might still be circulating and contributing to the evolution of IBV in Australia. PMID- 20574644 TI - Characterization of Rhynchosia yellow mosaic Yucatan virus, a new recombinant begomovirus associated with two fabaceous weeds in Yucatan, Mexico. AB - Rhynchosia minima (L.) DC. (Fabaceae) plants exhibiting bright golden mosaic symptoms were previously associated with begomovirus infection in Yucatan, Mexico [1]. To characterize the begomovirus infecting these plants, the complete bipartite genome was cloned and sequenced. Sequence comparisons indicated that the virus was distinct from all other begomoviruses known to date, including those previously identified from symptomatic R. minima, and the name Rhynchosia yellow mosaic Yucatan virus (RhYMYuV) is proposed. Pairwise comparisons indicated that RhYMYuV DNA-A [2,597 nt, (EU021216)] and DNA-B [2,542 nt, (FJ792608)] components shared the highest nt sequence identity with Cabbage leaf curl virus (CaLCuV), 87% for component A and 71% for component B. Phylogenetic analysis indicated that both components of RhYMYuV are most closely related to other New World begomoviruses, having as closest relatives immediate outliers to the major Squash leaf curl virus (SLCV) clade. Recombination analysis of the RhYMYuV genome indicated that the DNA-A component has arisen through intermolecular recombination. R. minima plants inoculated with the monomeric clones developed a bright yellow mosaic similar to symptoms observed in naturally infected plants, confirming that the clones were infectious. Nicotiana benthamiana plants biolistically inoculated with monomeric clones developed curling and chlorosis in the newly emerging leaves. RhYMYuV was also detected in symptomatic Desmodium sect. Scorpiurus Benth. (Fabaceae) that were collected near the RhYMYuV-infected plants. PMID- 20574645 TI - Molecular and enzymatic characterization of a subfamily I.4 lipase from an edible oil-degrader Bacillus sp. HH-01. AB - An edible-oil degrading bacterial strain HH-01 was isolated from oil plant gummy matter and was classified as a member of the genus Bacillus on the basis of the nucleotide sequence of the 16S rRNA gene. A putative lipase gene and its flanking regions were cloned from the strain based on its similarity to lipase genes from other Bacillus spp. The deduced product was composed of 214 amino acids and the putative mature protein, consisting of 182 amino acids, exhibited 82% amino acid sequence identity with the subfamily I.4 lipase LipA of Bacillus subtilis 168. The recombinant product was successfully overproduced as a soluble form in Escherichia coli and showed lipase activity. The gene was, therefore, designated as lipA of HH-01. HH-01 LipA was stable at pH 4-11 and up to 30 degrees C, and its optimum pH and temperature were 8-9 and 30 degrees C, respectively. The enzyme showed preferential hydrolysis of the 1(3)-position ester bond in trilinolein. The activity was, interestingly, enhanced by supplementing with 1 mM CoCl(2), in contrast to other Bacillus lipases. The lipA gene seemed to be constitutively transcribed during the exponential growth phase, regardless of the presence of edible oil. PMID- 20574646 TI - Marinimicrobium haloxylanilyticum sp. nov., a new moderately halophilic, polysaccharide-degrading bacterium isolated from Great Salt Lake, Utah. AB - A new moderately halophilic, strictly aerobic, Gram-negative bacterium, strain SX15(T), was isolated from hypersaline surface sediment of the southern arm of Great Salt Lake (Utah, USA). The strain grew on a number of carbohydrates and carbohydrate polymers such as xylan, starch, carboxymethyl cellulose and galactomannan. The strain grew at salinities ranging from 2 to 22% NaCl (w/v). Optimal growth occurred in the presence of 7-11% NaCl (w/v) at a temperature of 35 degrees C and a pH of 6.7-8.2. Major whole-cell fatty acids were C16:0 (30.5%), C18:0 (14.8%), C18:1omega7c (13.1%) and C12:0 (7.8%). The G+C content of the DNA was 60 +/- 0.5 mol%. By 16S rRNA gene sequence analysis, strain SX15(T) was shown to be affiliated to members of the gammaproteobacterial genus Marinimicrobium with pair wise identity values of 92.9-94.6%. The pheno- and genotypic properties suggest that strain SX15(T) represents a novel species of the genus Marinimicrobium for which the name Marinimicrobium haloxylanilyticum is proposed. The type strain is SX15(T) (= DSM 23100(T) = CCUG 59572(T)). PMID- 20574647 TI - Substance abuse treatment programs' data management capacity: an exploratory study. AB - Despite treatment improvement and performance management imperatives, little research describes the data management capacity of substance abuse treatment programs, and useful metrics are not available to gauge capacity. This exploratory study evaluates clinical and administrative data management at eight substance abuse treatment programs in four US states to identify factors for developing an appropriate metric. Findings indicate that programs tend to manage data inefficiently and have few protocols guiding information management. Barriers to better data management included lack of integrated information technology (IT) systems; limited funding, time, and staff for developing and implementing IT-related changes; and divergent staff skills in and attitudes toward IT. This snapshot of substance abuse treatment programs' data management capabilities suggests a need for a metric to examine data management capability in these settings. Infusion of expertise, training, and funding are needed to improve substance abuse treatment programs' IT-related systems and data management processes. PMID- 20574648 TI - Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study. AB - Our aim was to assess the ability of tocilizumab monotherapy to reduce progressive structural joint damage in rheumatoid arthritis patients at high risk of progression. This study was a subanalysis from a prospective 1-year, multicenter, X-ray-reader-blinded, randomized controlled trial of tocilizumab [Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 Inhibitor (SAMURAI) trial]. All patients were categorized into two or three groups according to four independent predictive markers for progressive joint damage [urinary C-terminal crosslinking telopeptide (uCTX-II), urinary pyridinoline/deoxypyridinoline (uPYD/DPD) ratio, body mass index (BMI), and joint space narrowing (JSN) score at baseline]. One-year progression of joint destruction was assessed in high-risk versus low-risk groups receiving tocilizumab monotherapy and compared with patients receiving conventional disease modifying antirheumatic drugs (DMARDs) (n = 157 and 145, respectively). In patients at high risk of progression of erosion as estimated by high uCTX-II, uPYD/DPD, or low BMI, and at high risk of progression of JSN as estimated by low BMI or high JSN score, the 52-week changes in radiological erosion and JSN, respectively, were significantly less in patients treated with tocilizumab monotherapy compared with those receiving DMARDs for each type of risk factor. In patients at low risk, those receiving tocilizumab also progressed less than those on DMARDs, although the difference did not reach statistical significance. Tocilizumab monotherapy is more effective in reducing radiological progression in patients presenting with risk factors for rapid progression than in low-risk patients. Patients at high risk for progression may benefit more from tocilizumab treatment. PMID- 20574649 TI - Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. AB - The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naive patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX. PMID- 20574650 TI - Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis. AB - Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients >= 50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08-5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine. PMID- 20574652 TI - Meconium pseudocyst. PMID- 20574651 TI - ADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity. AB - ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ADAMTS-2 is also able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillary-like structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2. PMID- 20574653 TI - Melanotic neuroectodermal tumor of the calvarium. PMID- 20574654 TI - The use of cryoplasty in a benign ureteric stricture. AB - Ureteral stricture is one of the most common complications following renal transplant. Current treatment options are limited to mainly surgery or balloon dilation, but mixed results and refractory cases present the opportunity for alternative treatments. Anterograde balloon cryoplasty of a benign ureteric stricture was performed in a renal transplant patient, after attempts with ballooning and stenting had failed. A 2-year follow-up demonstrates normal creatinine and no hydronephrosis on US images. PMID- 20574655 TI - Generalized cystic lymphangiomatosis. PMID- 20574656 TI - Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk. AB - Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells. PMID- 20574657 TI - Leisure-time physical activity, cardiovascular risk factors and mortality during a 34-year follow-up in men. AB - The inverse relationship between physical activity and mortality may be confounded by socioeconomic factors, cardiovascular risk factors and inverse causality. We investigated long-term association between self-reported regular physical activity and mortality in a socioeconomically homogeneous, initially healthy middle-aged (mean age 47) male cohort (the Helsinki Businessmen Study). In 1974, the men were assessed with questionnaires, clinical and laboratory examinations. Cardiovascular disease (CVD) risk factors (including body mass index [BMI], age, cholesterol, glucose, systolic blood pressure and smoking) and details of physical activity of 782 men were available. Leisure time physical activity was collapsed into 3 categories: low (n = 148), moderate (n = 398) and high activity (n = 236). Physical activity was also briefly assessed in questionnaire surveys in 1985-1986 and in 2000. Total mortality up to 2007 was retrieved from the Central Population Register. Altogether 295 men (37.7%) died during the 34-year follow-up, and leisure-time physical activity was significantly related to mortality in a step-wise manner: 45.9% (n = 68), 37.7% (n = 150), and 32.6% (n = 77) died in the low, moderate, and high activity groups, respectively (P < 0.001). With high activity group as referent and adjusted for midlife CVD risk, perceived health and fitness at baseline, hazard ratio for total mortality was 1.21 (95% confidence interval: 0.90, 1.62), and 1.61 (95% confidence interval: 1.13, 2.30) in the moderate and low activity groups, respectively. CONCLUSION: During the 34-year follow-up, leisure-time physical activity in initially healthy middle-aged men had a graded association with reduced mortality that was independent of CVD risk, glucose and BMI. PMID- 20574658 TI - Determination of five phthalate monoesters in human urine using gas chromatography-mass spectrometry. AB - We have developed a gas chromatography-mass spectrometry (GC-MS) method to determine five phthalate monoesters (monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), monoisononyl phthalate (MINP) and monobenzyl phthalate (MBz)) in human urine. Human urine samples were subjected to enzymatic deconjugation of the glucuronides followed by extraction with hexane. The extracted phthalate monoesters were methylated with diazomethane, purified on a Florisil column and then subjected to GC-MS analysis. The recoveries from urine spiked with five phthalate monoesters were 86.3%-119% with coefficients of variation of 0.6%-6.1%. We measured phthalate monoester levels in human urine by analyzing 36 samples from volunteers. MBP and MEP were detected in all samples, and their median concentrations were 60.0 and 10.7 ng/mL, respectively. MBzP and MEHP were found in 75% and 56% of samples, and their median concentrations were 10.9 and 5.75 ng/mL, respectively. MINPs were not detected in most samples (6% detectable). Women had significantly (p < 0.05) higher mean concentrations of MBP and MEP than men. The estimated daily exposure levels for the four parent phthalates excluding diisononyl phthalate ranged from 0.27 to 5.69 mug/kg/day (median). PMID- 20574659 TI - Impact of positron emission tomography/computed tomography in the management of patients with epithelial ovarian carcinoma after treatment. AB - PURPOSE: The aims of this study were to compare the usefulness and reliability of integrated whole-body positron emission tomography/computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) with those of contrast-enhanced multidetector CT during regular follow-up in patients after initial treatment of ovarian cancer, to assess the impact of FDG-PET/CT on the confirmation of recurrence, restaging, and clinical management of patients, and to determine the incremental information provided by PET/CT. METHODS: A retrospective review was performed on 19 ovarian cancer patients who underwent a total of 30 FDG-PET/CT and contrast-enhanced multidetector CT scans. The following information was obtained: the clinical information of the patients; the results of FDG-PET/CT and contrast-enhanced multidetector CT, particularly with regard to the impact on the diagnosis of recurrence; information on the localization and number of diseases; and the impact on subsequent clinical management. RESULTS: Both FDG-PET/CT and contrast-enhanced multidetector CT had very high sensitivity and specificity for the detection of recurrent ovarian cancer. Contrast-enhanced multidetector CT was considered the more accurate imaging modality for detecting recurrence, whereas FDG-PET/CT was proven more effective for detecting large numbers of small lesions. When comparing the impact on the choice of a management plan, both FDG PET/CT and contrast-enhanced multidetector CT were found to be significantly effective at predicting the locations of recurrence. CONCLUSIONS: Both integrated FDG-PET/CT and contrast-enhanced multidetector CT are sensitive surveillance modalities for the detection of recurrent ovarian cancer; the use of both modalities aids decisions on treatment plans and may ultimately have a favorable impact on prognosis. However, contrast-enhanced multidetector CT is recommended for the regular follow-up for ovarian cancer patients after initial treatment. PMID- 20574660 TI - Engineering of a wheat germ expression system to provide compatibility with a high throughput pET-based cloning platform. AB - Wheat germ cell-free methods provide an important approach for the production of eukaryotic proteins. We have developed a protein expression vector for the TNT((R)) SP6 High-Yield Wheat Germ Cell-Free (TNT WGCF) expression system (Promega) that is also compatible with our T7-based Escherichia coli intracellular expression vector pET15_NESG. This allows cloning of the same PCR product into either one of several pET_NESG vectors and this modified WGCF vector (pWGHisAmp) by In-Fusion LIC cloning (Zhu et al. in Biotechniques 43:354-359, 2007). Integration of these two vector systems allowed us to explore the efficacy of the TNT WGCF system by comparing the expression and solubility characteristics of 59 human protein constructs in both WGCF and pET15_NESG E. coli intracellular expression. While only 30% of these human proteins could be produced in soluble form using the pET15_NESG based system, some 70% could be produced in soluble form using the TNT WGCF system. This high success rate underscores the importance of eukaryotic expression host systems like the TNT WGCF system for eukaryotic protein production in a structural genomics sample production pipeline. To further demonstrate the value of this WGCF system in producing protein suitable for structural studies, we scaled up, purified, and analyzed by 2D NMR two (15)N , (13)C-enriched human proteins. The results of this study indicate that the TNT WGCF system is a successful salvage pathway for producing samples of difficult-to express small human proteins for NMR studies, providing an important complementary pathway for eukaryotic sample production in the NESG NMR structure production pipeline. PMID- 20574662 TI - Learning expressive percussion performance under different visual feedback conditions. AB - A study was conducted to test the effect of two different forms of real-time visual feedback on expressive percussion performance. Conservatory percussion students performed imitations of recorded teacher performances while receiving either high-level feedback on the expressive style of their performances, low level feedback on the timing and dynamics of the performed notes, or no feedback. The high-level feedback was based on a Bayesian analysis of the performances, while the low-level feedback was based on the raw participant timing and dynamics data. Results indicated that neither form of feedback led to significantly smaller timing and dynamics errors. However, high-level feedback did lead to a higher proficiency in imitating the expressive style of the target performances, as indicated by a probabilistic measure of expressive style. We conclude that, while potentially disruptive to timing processes involved in music performance due to extraneous cognitive load, high-level visual feedback can improve participant imitations of expressive performance features. PMID- 20574661 TI - Decomposing rhythm processing: electroencephalography of perceived and self imposed rhythmic patterns. AB - Perceiving musical rhythms can be considered a process of attentional chunking over time, driven by accent patterns. A rhythmic structure can also be generated internally, by placing a subjective accent pattern on an isochronous stimulus train. Here, we investigate the event-related potential (ERP) signature of actual and subjective accents, thus disentangling low-level perceptual processes from the cognitive aspects of rhythm processing. The results show differences between accented and unaccented events, but also show that different types of unaccented events can be distinguished, revealing additional structure within the rhythmic pattern. This structure is further investigated by decomposing the ERP into subcomponents, using principal component analysis. In this way, the processes that are common for perceiving a pattern and self-generating it are isolated, and can be visualized for the tasks separately. The results suggest that top-down processes have a substantial role in the cerebral mechanisms of rhythm processing, independent of an externally presented stimulus. PMID- 20574663 TI - Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. AB - PURPOSE: A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens. METHODS: This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25 mg intravenously) and dexamethasone (8 mg intravenously) before chemotherapy, while the other was administered the same regimen on day 1 followed by dexamethasone 8 mg orally on days 2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days 1-5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint. RESULTS: Of 332 chemotherapy-naive patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day 1 (n = 166), and 71.1% for those also administered dexamethasone on days 2 and 3 (n = 166; difference -3.6% (95% confidence interval, -13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0-24 h post chemotherapy; 88.6% versus 84.3%; P = 0.262) and delayed phases (days 2-5; 68.7% versus 77.7%; P = 0.116). CONCLUSIONS: Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3 days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens. PMID- 20574664 TI - The development and validation of a quality-of-life questionnaire for head and neck cancer patients with enteral feeding tubes: the QOL-EF. AB - PURPOSE: To develop a questionnaire that measures the impact of enteral feeding tubes (EFTs) on the quality of life (QOL) of head and neck cancer (HNC) patients METHODS: The development of the questionnaire (QOL-EF) was done in four phases. Phase 1-3 included: (1) literature review and consultation with an expert focus group (item generation), (2) pilot-testing in 12 patients and, (3) judgmental item reduction. In phase 4, the QOL-EF, FACT-H&N, and UW-QOL were administered to a cross-sectional group of HNC patients on active EFT feeding to test the reliability and validity of the QOL-EF. RESULTS: A 20-item QOL-EF was developed. In phase 4, 72 patients were accrued over 2.5 years, 31 of which were part of the test-retest subgroup. Cronbach's alpha for the QOL-EF was 0.73, and test-retest reliability was 0.83. Moderate correlations were observed between scores for the QOL-EF and both the FACT-H&N (-0.58) and the UW-QOL (-0.42). CONCLUSIONS: The QOL EF is a treatment-specific QOL instrument developed and validated for use in HNC patients with EFTs. It may become an important tool in evaluating treatment outcomes and complications in these patients. PMID- 20574665 TI - The initial development of an instrument to assess the psychosocial needs and unmet needs of young people who have a parent with cancer: piloting the offspring cancer needs instrument (OCNI). AB - PURPOSE: This study aimed to identify the psychosocial needs of young people (12 24 years) who have a parent with cancer and to assess whether these needs are being met. This paper also presented the initial steps in the development of a need-based measure-the Offspring Cancer Needs Instrument (OCNI). METHODS: Study 1 used qualitative methods to identify the needs of the target population, including a focus group (n = 6), telephone interviews (n = 8) and staff survey (n = 26). In study 2, a quantitative survey design was employed where 116 young people completed the 67-item OCNI and either the total difficulties score of the Strengths and Difficulties Questionnaire (SDQ-TD; 12-17-year-old) or Depression, Anxiety, Stress Scale-21 (DASS-21) (18-24-year-old). Tests of reliability (Cronbach's alpha) were used to assess the properties of each domain, where a level of 0.70 was deemed satisfactory as per scale guidelines. Construct validity was assessed by testing the proposed relationship between unmet needs and functioning where a coefficient of 0.03 was deemed satisfactory. RESULTS: The qualitative data yielded eight need domains (information, peer support, feelings, carer support, family, school/work environment, access to support and respite and recreation), which were subsequently used to inform the item content of the OCNI. The survey data revealed that 90% of young people endorsed 10 or more needs, and nearly a quarter indicated >50 needs. It was also found that these needs often go unmet: 87% of the participants had at least one unmet need, 43% reported >10 and just under a quarter had >20 unmet needs. The two highest reported unmet needs related to understanding from friends and assistance with concentrating and staying on task. The OCNI exhibited face and content validity and acceptable reliability for most of the domains. Cronbach's alpha ranged from 0.64 (access to support) to 0.92 (information). Preliminary construct validity was assessed through the hypothesised positive relationship between unmet needs and the SDQ-TD for 12-17-year-old participants (r = 0.33, p<0.001) and the DASS-21 for 18-24 year-old participants (depression, r = 0.77, p < 0.001; anxiety, r = 0.66, p < 0.001; stress: r = 0.56, p < 0.05). CONCLUSION: Young people (aged 12-24 years) who have a parent with cancer report a complex array of needs, many of which go unmet. The preliminary findings reported may be used to inform service providers in the development and evaluation of need-based programs to redress these unmet needs and thus ameliorate the effects of parental cancer. Services addressing information and school-based interventions are particularly pertinent given these current results. PMID- 20574666 TI - Use of antiemetics in the management of chemotherapy-related nausea and vomiting in current UK practice. AB - PURPOSE: The main aim of the present study was to assess antiemetic prescriptions used during chemotherapy and identify if these are in agreement with internationally agreed consensus guidelines (MASCC/ASCO). METHODS: A web-based survey in the UK was carried out collecting data through a 32-item questionnaire using a snowball sampling technique and the email lists of two large oncology societies in the country. RESULTS: The participants were 154 oncologists and oncology nurse prescribers. Data showed a great variability in antiemetic prescriptions used, most not been in accordance with MASCC/ASCO consensus guidelines. The variability was also reflected in the doses of antiemetics used. Overall, clinicians undertreated patients receiving highly emetogenic chemotherapy and overtreated patients receiving low and minimally emetogenic chemotherapy. Eight of ten clinicians, however, prescribed antiemetics in accordance with consensus guidelines in moderately emetogenic chemotherapy. There was more agreement between clinicians and guidelines for acute nausea/vomiting and less for delayed symptoms. The uptake of MASCC/ASCO guidelines was minimal. CONCLUSIONS: The low level of agreement between actual clinical practice and evidence-based consensus guidelines may be one of the reasons for the considerable incidence of chemotherapy-related nausea and vomiting. There is a need to utilise consensus guidelines more widely and educate clinicians on this aspect of supportive care. PMID- 20574667 TI - Expression of ethylene response factor JERF1 in rice improves tolerance to drought. AB - Ethylene response factor (ERF) proteins regulate a variety of stress responses in plant. JERF1, a tomato ERF protein, can be induced by abscisic acid (ABA). Overexpression of JERF1 enhanced the tolerance of transgenic tobacco to high salt concentration, osmotic stress, and low temperature by regulating the expression of stress-responsive genes by binding to DRE/CRT and GCC-box cis-elements. In this research, we further report that overexpression of JERF1 significantly enhanced drought tolerance of transgenic rice. The overexpression activated the expression of stress-responsive genes and increased the synthesis of the osmolyte proline by regulating the expression of OsP5CS, encoding the proline biosynthesis key enzyme deltal-pyrroline-5-carboxylate synthetase. JERF1 also activated the expression of two ABA biosynthesis key enzyme genes, OsABA2 and Os03g0810800, and increased the synthesis of ABA in rice. Analysis of cis-elements of JERF1 targeted genes pointed to the existence of DRE/CRT and/or GCC box in their promoters, indicating that JERF1 could activate the expression of related genes in rice by binding to these cis-elements. Unlike some other ERF proteins, constructive overexpression of JERF1 did not change the growth and development of transgenic rice, which makes JEFR1 a potentially useful source in breeding for greater tolerance to abiotic stress. PMID- 20574668 TI - Are specific allergen sensitivities inherited? AB - A family history of an allergic condition is a well-accepted risk factor for the development of an allergic condition in an individual, particularly for allergic disorders such as asthma, eczema, and allergic rhinitis. However, the question of whether specific allergen sensitization is inherited requires a complicated answer, as environmental exposure plays an important role in the development of allergen-specific IgE. This article summarizes the findings of recent studies in the literature regarding what is known about the inheritance of specific allergens. Overall, properly collected and analyzed data appear to both support and refute the hypothesis that specific allergen sensitization is inherited, even when attempting to account for the complexities of varying study methodologies and the evaluation of diverse populations and communities. PMID- 20574669 TI - The rate and magnitude of atmospheric pressure change that aggravate pain-related behavior of nerve injured rats. AB - Complaints of patients with chronic pain may increase when the weather changes. The exact mechanism for weather change-induced pain has not been clarified. We have previously demonstrated that artificially lowering barometric pressure (LP) intensifies pain-related behaviors in rats with neuropathic pain [chronic constriction injury (CCI) and spinal nerve ligation (SNL)]. In the present study, we examined the rate and magnitude of LP that aggravates neuropathic pain. We measured pain-related behaviors [number of paw lifts to von Frey hair (VFH) stimulation] in awake rats after SNL or CCI surgery, and found that rates of decompression >=5 hPa/h and >=10 hPa/h and magnitudes of decompression >=5 hPa and >=10 hPa augmented pain-related behaviors in SNL and CCI rats, respectively. These results indicate that LP within the range of natural weather patterns augments neuropathic pain in rats, and that SNL rats are more sensitive to LP than CCI rats. PMID- 20574670 TI - Phenological observations of grass curing in Germany. AB - The degree of grass curing, i.e. the proportion of dehydrated dead grass per unit grassland area, is one of the most important parameters affecting grassland fire risk and fire behaviour. The objective of the present study was to develop a simple relationship between grass moisture and grass curing to use as an input into the next-generation fire-danger rating models of the Deutscher Wetterdienst. Seasonal changes in yellow and green portions of grass plots were estimated visually at weekly intervals. At the same time, the grass-moisture content was measured gravimetrically after destructive sampling. Regression analysis revealed an exponential relationship between decreasing leaf moisture and increasing yellowing level, in rough agreement with findings reported from Australia and North America. PMID- 20574672 TI - Prognostic factors for skeletal complications from metastatic bone disease in breast cancer. AB - Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P < 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy. In conclusion, this model identified several prognostic factors that may be useful in routine clinical care. Validation of these factors in a separate dataset and generation of a prognostic risk score are recommended next steps. PMID- 20574673 TI - Targeted treatment and new agents in follicular lymphoma. AB - Follicular lymphomas are indolent diseases, which, while highly responsive to chemotherapy, remain incurable. Various combinations of standard chemotherapy drugs have not improved the outcome. The availability of effective and well tolerated monoclonal antibodies (MoAbs), such as rituximab, provided the first evidence that new agents could prolong the survival of these patients. An increasing number of effective drugs are now being evaluated either as single agents or in combinations. These include chemotherapy drugs, bendamustine and bortezomib, MoAbs, other agents that inhibit various cellular pathways including spleen tyrosine kinase, mammalian target of rapamycin, PI3-kinase and apoptosis, and drugs that target the tumor microenvironment, such as the immunomodulatory agent lenalidomide. Rational development of combination strategies, including correlative studies to enhance our understanding of the mechanisms of action and resistance of the drugs, and the biology of the tumor, will continue to improve the outcome of patients with follicular lymphoma. PMID- 20574674 TI - Down-regulation of HSP60 expression by RNAi increases lipopolysaccharide- and cerulein-induced damages on isolated rat pancreatic tissues. AB - The objective of this study was to investigate the function of heat shock protein 60 (HSP60) on pancreatic tissues by applying HSP60 small interfering RNA (siRNA) to reduce HSP60 expression. Rat pancreas was isolated and pancreatic tissue snips were prepared, cultured, and stimulated with low and high concentrations of cerulein (10(-11) and 10(-5) mol/L) or lipopolysaccharide (LPS, 10 and 20 MUg/mL). Before the stimulation and 1 and 4 h after the stimulation, the viability and the level of trypsinogen activation peptide (TAP) in the tissue fragments were determined and the levels of tumor necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6) in the culture supernatants were measured. Real time PCR and Western blotting were used to evaluate the HSP60 mRNA and protein expression. After the administration of siRNA to inhibit HSP60 expression in the isolated tissues, these injury parameters were measured and compared. The pancreatic tissues in the control (mock-interfering) group showed a decreased viability to varying degrees after being stimulated with cerulein or LPS, and the levels of TAP, TNF-alpha, and IL-6 increased significantly (p < 0.05) in the tissues and/or in the culture supernatant. The expressions of HSP60 mRNA and protein were raised moderately after stimulating 1 h with low concentrations of cerulein or LPS, but decreased with high concentrations of the toxicants. In particular, the expression of HSP60 protein was reduced significantly (p < 0.05) when the tissues were stimulated by the two toxicants for 4 h. In contrast, the tissue fragments in which HSP60 siRNA was applied showed much lower tissue viability (p < 0.01) and higher levels of TNF-a, IL-6, and TAP (p < 0.01) in the tissues or culture supernatant after stimulating with the toxicants at the same dose and for the same time duration as compared with those of the control groups (p < 0.05). The results indicated that both cerulein and LPS can induce injuries on isolated pancreatic tissues, but the induction effects are dependent on the duration of the stimulation and on the concentrations of the toxicants. HSP60 siRNA reduces HSP60 expression and worsens the cerulein- or LPS-induced injuries on isolated pancreatic tissues, suggesting that HSP60 has a protective effect on pancreatic tissues against these toxicants. PMID- 20574671 TI - Triple negative breast cancer in Korea-distinct biology with different impact of prognostic factors on survival. AB - We analyzed breast cancer subtypes using Korean Breast Cancer Society Registration Program data to compare clinical features and prognosis for triple negative breast cancer (TNBC). A cohort of 26,767 breast cancer patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), HER2+ (ER-, PR-, HER2+), and triple-negative (ER-, PR-, HER2-). Clinicopathologic factors were evaluated. The luminal A (14,437 patients, 53.9%) subtype was the largest in our study. Compared with luminal A subtype, TNBC correlated with younger age, more aggressive characteristics and poor overall survival and breast cancer-specific survival. The hazard rate showed a peak at 24 months for the TNBC subtype, but after 60 months, risk was similar to that of the luminal A subtype. Higher T, N stage and histologic grade, and lymphatic and vascular invasion showed poor prognosis in TNBC patients, but on multivariate analysis only histologic grade and ki-67 status were related. Young age was related to poor prognosis in the luminal A subtype, however, age was not related to prognosis in the TNBC subtype. Of the 5,586 TNBC patients, 282 patients (7.11%) expired within 3 years of diagnosis. T and N stage and grade were significantly associated with prognosis on multivariate analysis. TNBC subtype is characterized by younger age with poorer outcome. However, younger age is not related to prognosis, and mortality risk decreases to that of the luminal A subtype, which is known to have the best prognosis after a few years. PMID- 20574675 TI - Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions. AB - Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 +/- 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans. PMID- 20574676 TI - The reliability of the IL-6, sIL-6R and sgp130 response to a preloaded time trial. AB - Interleukin-6 (IL-6) is a cytokine that can mediate numerous biological actions including fatigue. Circulating IL-6 increases during prolonged exercise, and furthermore, the signalling receptors sIL-6R and sgp130 are also increased. The variability of the response of these markers to exercise is unknown; therefore, we examined the changes in these markers to a preloaded time trial bout of running. Nine males performed three identical trials where participants ran at 60% vVO2max for 2 h interspersed with 30 s at 90% vVO2max every 10 min, followed by a 5-km time trial. Blood samples were drawn at baseline, following the 2-h bout, post time trial, 1 h post time trial and the following morning. Results showed that between-subject variability (CVg) was greater than within-subject variation (CVi) for the three markers. IL-6, sIL-6R and sgp130 demonstrated a CVi of 15.3-25.5%, 15.0-17.6% and 6.2-9.4% variation, respectively, across the time points. When the data from the second and third trials were analysed independently, CVi was reduced which is supported by the time trial results for which CVi improve (4.7-2.4%). In conclusion, the results indicate that a large variation in response to exercise can be reduced following a habituation trial. PMID- 20574677 TI - The influence of menthol on thermoregulation and perception during exercise in warm, humid conditions. AB - Menthol has recently been added to various cooling products that claim to enhance athletic performance. This study assessed the effect of two such solutions during exercise in warm, humid conditions. Twelve participants (22 +/- 2.9 years; VO2peak 47.4 +/- 6.2 mL kg(-1) min(-1)) completed a peak power (PO(peak)) test and three separate exercise bouts in 30 degrees C and 70% relative humidity after being sprayed with 100 mL of water containing either 0.05 or 0.2% l-menthol, or a control spray. During each trial, participants underwent 15 min of rest, spraying, 15 min of rest and 45 min of exercise at 45% of PO(peak). The following variables were measured: rectal temperature (T (re)), sweat rate (SR), skin blood flow (SBF), heart rate (HR), thermal comfort (TC) and sensation (TS) votes, irritation (IRR) and rating of perceived exertion (RPE). Mean skin (MST) and body temperatures (Tbody) were calculated. There was no significant difference in MST, Tbody SR, SBF, HR, TC or RPE between conditions. Spraying with 0.2% menthol significantly (P < 0.05) elevated T (re) by 0.2 degrees C compared to the other conditions. Both menthol sprays caused participants to feel significantly cooler than control spraying (P = 0.001), but 0.2% spraying induced significantly cooler sensations (P = 0.01) than 0.05% spraying. Both menthol sprays induced greater irritation (P < 0.001) than control spraying. These findings suggest that 0.05% menthol spraying induced cooler upper body sensations without measurable thermoregulatory impairment. T (re) was significantly elevated with 0.2% spraying. Irritation persisted with both menthol sprays while TC remained unchanged, suggesting a causal relationship. The use in sport of a spray similar to those tested here remains equivocal. PMID- 20574678 TI - Faster oxygen uptake kinetics during recovery is related to better repeated sprinting ability. AB - This study was designed to test the hypothesis that subjects having faster oxygen uptake (VO(2)) kinetics during off-transients to exercises of severe intensity would obtain the smallest decrement score during a repeated sprint test. Twelve male soccer players completed a graded test, two severe-intensity exercises, followed by 6 min of passive recovery, and a repeated sprint test, consisting of seven 30-m sprints alternating with 20 s of active recovery. The relative decrease in score during the repeated sprint test was positively correlated with time constants of the primary phase for the VO(2) off-kinetics (r = 0.85; p < 0.001) and negatively correlated with the VO(2) peak (r = -0.83; p < 0.001). These results strengthen the link found between VO(2) kinetics and the ability to maintain sprint performance during repeated sprints. PMID- 20574679 TI - Patterns of photoassimilate translocation to reproductive shoots from adjacent shoots in Camellia sasanqua by manipulation of sink-source balance between the shoots. AB - To know to what extent reproductive shoots are autonomous in Camellia sasanqua, we manipulated the sink-source balance between the reproductive shoots and their adjacent shoots by selecting vegetative or reproductive adjacent shoots, or defoliating the reproductive shoots, and photosynthetically labeled adjacent shoots with (13)C. The atom% of (13)C did not increase in the unlabeled shoots that had leaves, whereas that in the defoliated, unlabeled shoot was significantly increased. These results indicated that the pattern of translocation of photoassimilates to adjacent reproductive shoots occurs depending on the sink-source balance between shoots. PMID- 20574680 TI - Wind tunnel and field assessment of pollen dispersal in soybean [Glycine max (L.) Merr.]. AB - Although genetically modified (GM) soybean has never been cultivated commercially in Japan, it is essential to set up the isolation distance required to prevent out-crossing between GM and conventional soybean in preparation for any future possibility of pollen transfer. The airborne soybean pollen was sampled using some Durham pollen samplers located in the range of 20 m from the field edge. In addition, the dispersal distance was assessed in a wind tunnel under constant air flow and then it was compared with the anticipated distances based on the pollen diameter. In the field, the maximum pollen density per day observed was 1.235 grains cm(-2) day(-1) at three observation points within 2.5 m from the field and inside the field the mean density did not reach the rate of 1 grain cm(-2 )day( 1) during 19 flowering days. The results of the wind tunnel experiment also showed that the plants had almost no airborne release of pollen and the dispersal distance was shorter than theoretical value due to clustered dispersal. This study showed little airborne pollen in and around the soybean field and the dispersal is restricted to a small area. Therefore, wind-mediated pollination appears to be negligible. PMID- 20574681 TI - Is selenium deficiency really the cause of Keshan disease? AB - Keshan disease (KD) is a dilated cardiomyopathy closely related with a diet deficient in the mineral selenium. It is named for the northeastern Chinese county Keshan, where the disease prevalence is high because of selenium-deficient soil. KD is a gene-environment interaction disease. Here, we used stepwise multiple regression analysis to analyze the risk factors of the disease and the main clinical features in 71 KD patients and 290 controls. The variables analyzed included age, sex, family history of KD, blood selenium level, glutathione peroxidase-1 (GPx-1) activity, variance at codon198 in GPx-1 gene, residence in an endemic area, abnormal electrocardiography (ECG) findings, and cardiothoracic (CT) ratio. The main risk factors found were low GPx-1 activity, family history of KD and living in an endemic area. The main clinical features were increased cardiac load on ECG and increased CT ratio and Tei index. Public health and clinical prevention efforts could focus on increasing GPx-1 activity to address KD. Is selenium deficiency really the certain cause of KD? This is not at all a settled question. And further study is promptly required to investigate the etiology of KD. PMID- 20574682 TI - Age-dependent expression of apolipoprotein E in mouse cerebral cortex. AB - Apolipoprotein E (apoE) is predominantly a lipid transport protein involved in membrane repair and synaptic plasticity in brain. Its genotype is associated with late-onset sporadic and familial Alzheimer's disease (AD). Its expression increases when any injury takes place in the nervous system and in age-related disorders including AD. However, it is not clearly understood how the level of apoE changes in the normal aging brain. Therefore, we have analyzed the effect of age on apoE protein and mRNA level in the cerebral cortex of young, adult, and old male AKR strain mice. Western, northern, and RT-PCR results reveal that the level of apoE protein and mRNA is higher in young as compared to adult and then remains unchanged in old mouse cerebral cortex. This indicates that during normal aging, apoE level is maintained in old similar to adult and suggests involvement of other factors in maintaining apoE-mediated brain functions in old. PMID- 20574683 TI - Plasticity of opioid receptors in the female periaqueductal gray: multiparity induced increase in the activity of genes encoding for mu and kappa receptors and a post-translational decrease in delta receptor expression. AB - The periaqueductal gray (PAG) has been reported as a potential site for opioid regulation of behavioral selection. Opioid-mediated behavioral and physiological responses differ between nulliparous and multiparous females. This study addresses the effects of multiple reproductive experiences on MU-, kappa- and delta-opioid receptor (Oprm1, Oprk1, and Oprd1 respectively) gene activity and MU, kappa and delta protein expression (MOR, KOR and DOR respectively) in the PAG of the female rats. This was done by evaluating the opioid gene expression using real-time (RT-PCR) and quantification of each protein receptor by Western blot analysis. The RT-PCR results show that multiple reproductive experiences increase Oprm1 and Oprk1 gene expression. Western blot analysis revealed increased MOR and KOR while DOR protein was decreased in multiparous animals. Taken together, these data suggest that multiple reproductive experiences influence both gene activity and opioid receptor expression in the PAG. Post-translational mechanisms seem particularly relevant for DOR expression. Thus, opioid transmission in the PAG might be modulated by different mechanisms of multiparity-induced plasticity according to the opioid receptor type. PMID- 20574684 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalamus. Recently, we have shown that the PACAP receptor (PAC1-R) is expressed in reactive astrocytes following an in vivo stub wound brain injury. However, the functional role of PACAP has not yet been clarified. In order to investigate the effect of PACAP on the proliferation of reactive astrocytes, a scratch wound paradigm was applied to astrocytic monolayers. Following injury, there was an increase in PAC1-R and glial fibrillary acidic protein (GFAP) immunoreactivity in the astrocytes surrounding the scratch line. PACAP at concentrations of 10(-15) to 10(-7) M was applied immediately after scratching, and the proliferating astrocytes were visualized by multiple immunofluorescence labeling. The percentage of cells that colabeled for Ki67 (a marker of proliferating cells) and GFAP increased in the 10(-11)- and 10( 13)-M PACAP-treated groups. The proliferating astrocytes induced by PACAP treatment mainly occurred in the proximal wound area where many reactive astrocytes were observed. Pretreatment with the PACAP receptor antagonist PACAP6 38 significantly suppressed the PACAP-induced effects. These results strongly suggest that PACAP plays an important role in the proliferation of reactive astrocytes following nerve injury. PMID- 20574685 TI - Hemispheric differences in use-dependent corticomotor plasticity in young and old adults. AB - The aim of this study was to examine corticomotor excitability and plasticity following repetitive thumb abduction training in left and right hands of young and old adults. Electromyographic recordings were obtained from the abductor pollicis brevis (APB) muscle of 12 young (aged 18-27 years) and 14 old (aged 63 75 years) adults. Motor training consisted of 300 ballistic abductions of the thumb to maximize peak abduction acceleration, with each hand tested in a separate session. Transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) was used to assess changes in contralateral APB motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) before and after training. For young and old adults, APB MEP amplitude increased for both hands after training, which is indicative of use-dependent plasticity. However, the increase in MEP amplitude was 21% (P = 0.04) greater in the left (non dominant) hand compared with the right (dominant) hand. This occurred despite a 40% greater improvement in peak thumb abduction acceleration (motor learning) for the right hand in young subjects compared with the left hand in young subjects (P < 0.04) and the right hand in old subjects (P < 0.01). Furthermore, no difference in use-dependent plasticity was observed between young and old adults, and SICI remained unchanged following ballistic training for both hands in all subjects. These findings suggest that there is greater strengthening of corticomotor circuits for control of the left compared with the right hand during simple ballistic thumb training and that an age-related decline in motor learning was observed only in the dominant hand. In contrast to previous studies, these data also indicate that young and old adults can demonstrate similar use-dependent corticomotor plasticity during this simple thumb-training task. PMID- 20574686 TI - Specific vermal complex spike responses build up during the course of smooth pursuit adaptation, paralleling the decrease of performance error. AB - Contemporary theories of the cerebellum hold that the complex spike (CS) fired by cerebellar Purkinje cells (PCs) reports the error signal essential for motor adaptation, i.e., the CS serves as a teacher reducing the performance error. This hypothesis suggests a monotonic relationship between CS modulation and performance error: the modulation of CS responses should be maximal at adaptation onset and turn back to its pre-adaptation state when the error is nulled. An alternative viewpoint based on studies of saccades suggests that the modulation of the CS discharge builds up as performance error decreases, and maximum and stable CS modulation is found after adaptation has been completed (Catz et al. 2005). We wanted to know whether this pattern can be generalized to other forms of motor adaptation. We resorted to smooth-pursuit adaptation (SPA) as an example of cerebellar-dependent adaptation. SPA is induced by increasing or decreasing target velocity during pursuit initiation that leads to a gradual increase or decrease in eye velocity. We trained 2 rhesus monkeys and recorded CS from PC in vermal lobuli VI and VII during SPA. We find that SPA is accompanied by a pattern of CS firing, which at the onset of adaptation, i.e., when the error is large, is not modulated significantly. On the other hand, when initial eye velocity is stably increased or decreased by adaptation, the probability of CS occurrence during pursuit initiation decreases or increases, respectively. Overall, our results deviate from the predictions made by the classical error-coding concept. PMID- 20574687 TI - A body-centred frame of reference drives spatial priming in visual search. AB - Spatial priming in visual search is a well-documented phenomenon. If the target of a visual search is presented at the same location in subsequent trials, the time taken to find the target at this repeated target location is significantly reduced. Previous studies did not determine which spatial reference frame is used to code the location. At least two reference frames can be distinguished: an observer-related frame of reference (egocentric) or a scene-based frame of reference (allocentric). While past studies suggest that an allocentric reference frame is more effective, we found that an egocentric reference frame is at least as effective as an allocentric one (Ball et al. Neuropsychologia 47(6):1585-1591, 2009). Our previous study did not identify which specific egocentric reference frame was used for the priming: participants could have used a retinotopic or a body-centred frame of reference. Here, we disentangled the retinotopic and body centred reference frames. In the retinotopic condition, the position of the target stimulus, when repeated, changed with the fixation position, whereas in the body-centred condition, the position of the target stimulus remained the same relative to the display, and thus to the body-midline, but was different relative to the fixation position. We used a conjunction search task to assess the generality of our previous findings. We found that participants relied on body centred information and not retinotopic cues. Thus, we provide further evidence that egocentric information, and specifically body-centred information, can persist for several seconds, and that these effects are not specific to either a feature or a conjunction search paradigm. PMID- 20574688 TI - Gesture imitation in musicians and non-musicians. AB - Imitation plays a crucial role in the learning of many complex motor skills. Recent behavioral and neuroimaging evidence suggests that the ability to imitate is influenced by past experience, such as musical training. To investigate the impact of musical training on motor imitation, musicians and non-musicians were tested on their ability to imitate videoclips of simple and complex two-handed gestures taken from American Sign Language. Participants viewed a set of 30 gestures, one at a time, and imitated them immediately after presentation. Participants' imitations were videotaped and scored off-line by raters blind to participant group. Imitation performance was assessed by a rating of performance accuracy, where the arm, hand, and finger components of the gestures were rated separately on a 5-point scale (1 = unrecognizable; 5 = exact imitation). A global accuracy score (PAglobal) was calculated by summing the three components. Response duration compared to the model (%MTdiff), and reaction time (RT) were also assessed. Results indicated that musicians were able to imitate more accurately than non-musicians, reflected by significantly higher PAglobal and lower %MTdiff scores. Furthermore, the greatest difference in performance was for the fine-motor (finger) gesture component. These findings support the view that the ability to imitate is influenced by experience. This is consistent with generalist theories of motor imitation, which explain imitation in terms of links between perceptual and motor action representations that become strengthened through experience. It is also likely that musical training contributed to the ability to imitate manual gestures by influencing the personal action repertoire of musicians. PMID- 20574689 TI - Crossing the hands is more confusing for females than males. AB - A conflict between an egocentric and an external reference frame can be highlighted by examining the marked deficit observed with tactile temporal order judgments (TOJ) when the hands are crossed. The anecdotally-reported large individual differences in the magnitude of this crossed-hands deficit were explored here by testing a large group of participants (48; 24 female). Given that females have been shown to be more visually dependent than males in the potentially related rod-and-frame test (RFT), we hypothesized that females would show a larger influence of the external reference frame (i.e., a larger crossed hands deficit). As predicted, female participants produced larger tactile TOJ deficits compared to our male participants. We also administered the RFT in these participants with hands crossed and uncrossed. Crossing the hands increased the effect of the frame in the RFT, more so for females than males, further highlighting the potential difference in the way that each sex accommodates reference frame conflicts. Finally, examining the relation between the two tasks revealed a significant correlation, with larger frame effects associated with larger crossed-hands TOJ deficits, but this only held for males. We speculate that sex-specific differences in multisensory processing and spatial ability may explain why females are less able to disambiguate a crossed-hands posture than are males. PMID- 20574690 TI - Association between the angiotensin I-converting enzyme gene insertion/deletion polymorphism and endurance running speed in Japanese runners. AB - We investigated the association between the angiotensin I-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and endurance running performance in Japanese elite runners, including several Olympic athletes. The frequency of the I/I genotype was not significantly higher and the frequency of the D/D genotype was not significantly lower in elite runners compared with non-athletes. However, the frequency of the I/D genotype tended to be lower in elite runners than in non athletes. The best performance was significantly higher for runners with the D/D genotype than for those with the I/I genotype, and the average running speed was significantly higher for those with the combined D/D + I/D genotypes than for those with the I/I genotype. There were no I/I genotypes among the five fastest marathon runners. These results suggest that the D allele of the ACE gene I/D polymorphism is associated with a high level of human endurance. PMID- 20574692 TI - Human monoclonal antibodies to the insulin-like growth factor 1 receptor inhibit receptor activation and tumor growth in preclinical studies. AB - INTRODUCTION: The insulin-like growth factor type 1 (IGF-1) receptor contributes importantly to transformation and survival of tumor cells both in vitro and in vivo, and selective antagonists of the IGF-1 receptor (IGF-1R) activity represent an attractive experimental approach for human cancer therapy. METHODS: Using a phage display library, we identified several high-affinity fully human monoclonal antibodies with inhibitory activity against both human and rodent IGF.1Rs. RESULTS: These candidate therapeutic antibodies recognized several distinct epitopes and effectively blocked ligand-mediated receptor signal transduction and cellular proliferation in vitro. They also induced IGF-1R downregulation and catabolism following antibody-mediated endocytosis. These antibodies exhibited activity against human, primate, and rodent IGF-1Rs, and dose-dependently inhibited the growth of established human tumors in nude mice. CONCLUSION: These fully human antibodies therefore have the potential to provide an effective anti tumor biological therapy in the human clinical setting. PMID- 20574691 TI - Cardiovascular events in chronic dialysis patients: emphasizing the importance of vascular disease prevention. AB - Cardiovascular disease is the leading cause of death in both chronic kidney disease and peritoneal dialysis/hemodialysis patients. Vascular disease prevention in these patients is therefore important to reduce the incidence of cardiovascular events and the high morbidity and mortality. This Editorial discusses the traditional, (1) smoking, (2) dyslipidemia, (3) body mass index, (4) glycemic control and (5) blood pressure, and non-traditional, (1) anemia, (2) vitamin D/hyperparathyroidism, (3) calcium/phosphorus metabolism and (4) magnesium, risk factors in renal patients. Current evidence does not support routine statin use and antiplatelet medication to dialysis patients. Patient compliance and adherence to proposed measures could be essential to reduce cardiovascular events and mortality rates in this high-risk population. PMID- 20574693 TI - Epiflex((r)) a new decellularised human skin tissue transplant: manufacture and properties. AB - The manufacture and initial testing of a new human tissue transplant is described. Epiflex((r)) is a human acellular dermis transplant that is manufactured from skin recovered from screened consenting donors according to validated and approved methods. The transplant is approved as a drug in Germany. The safety, stability and usability of the transplant are discussed with respect to the results of sterility, residual moisture content and rehydration tests. Histological and confocal laser scanning microscopy experiments and analysis of oxygen and water vapour permeability demonstrate that the native extracellular matrix structure and transport properties of human connective tissue are retained in the transplant. Results from initial clinical investigations suggest that Epiflex((r)) can be used successfully in the treatment of burns, hypertrophic scars and as a transplant seeded with autologous dermal fibroblasts for soft tissue regeneration in settings with wound healing problems following multi-modal treatments for sarcomas of the extremities. PMID- 20574694 TI - Mapping of quantitative trait loci and development of allele-specific markers for seed weight in Brassica napus. AB - Seed weight is an important component of grain yield in oilseed rape (Brassica napus L.), but the genetic basis for the important quantitative trait is still not clear. In order to identify the genes for seed weight in oilseed rape, QTL mapping for thousand seed weight (TSW) was conducted with a doubled haploid (DH) population and an F(2) population. A complete linkage map of the DH population was constructed using 297 simple sequence repeat (SSR) markers. Among nine TSW QTLs detected, two major QTLs, TSWA7a and TSWA7b, were stably identified across years and collectively explained 27.6-37.9% of the trait variation in the DH population. No significant epistatic interactions for TSW detected in the DH population indicate that the seed weight variation may be primarily attributed to additive effects. The stability and significance of TSWA7a and TSWA7b were further validated in the F(2) population with different genetic backgrounds. By cloning BnMINI3a and BnTTG2a, two B. napus homologous genes to Arabidopsis thaliana, allele-specific markers were developed for TSWA5b and TSWA5c, two TSW QTLs on A5, respectively. The importance of the major and minor QTLs identified was further demonstrated by analysis of the allelic effects on TSW in the DH population. PMID- 20574695 TI - Plant volatile-induced aphid resistance in barley cultivars is related to cultivar age. AB - Recent studies have shown that volatile chemical interaction between certain barley (Hordeum vulgare) cultivars can cause reduced host plant acceptance by the aphid Rhopalosiphum padi, and that certain cultivars can induce this effect while others can respond. In this study, we tested whether inducing and responding capabilities are linked to year of release in Swedish two-rowed spring barley. Eighteen cultivars released between 1897 and 1992 were tested in randomly selected subsets with pairwise combinations of volatile emitters and receivers. Significantly reduced aphid acceptance as a result of exposure to volatiles from plants of a different cultivar were found in 24% of the cultivar combinations. In general, older cultivars had a higher degree of aphid resistance after barley volatile treatment than did younger cultivars. The inducing effect of the emitter was also related to date of emitter cultivar release but the time relationship was reversed. Combinations with a younger volatile emitter and an older volatile receiver gave the strongest reduction in aphid acceptance of treated plants. Linear relationships between microsatellite diversity of emitting cultivars and their efficiency as inducers indicated that younger cultivars might have a more unique odour, whereas older cultivars may be more sensitive to induction. PMID- 20574696 TI - Computational design of a lipase for catalysis of the Diels-Alder reaction. AB - Combined molecular docking, molecular dynamics (MD) and density functional theory (DFT) studies have been employed to study catalysis of the Diels-Alder reaction by a modified lipase. Six variants of the versatile enzyme Candida Antarctica lipase B (CALB) have been rationally engineered in silico based on the specific characteristics of the pericyclic addition. A kinetic analysis reveals that hydrogen bond stabilization of the transition state and substrate binding are key components of the catalytic process. In the case of substrate binding, which has the greater potential for optimization, both binding strength and positioning of the substrates are important for catalytic efficiency. The binding strength is determined by hydrophobic interactions and can be tuned by careful selection of solvent and substrates. The MD simulations show that substrate positioning is sensitive to cavity shape and size, and can be controlled by a few rational mutations. The well-documented S105A mutation is essential to enable sufficient space in the vicinity of the oxyanion hole. Moreover, bulky residues on the edge of the active site hinders the formation of a sandwich-like nearattack conformer (NAC), and the I189A mutation is needed to obtain enough space above the face of the alpha,beta-double bond on the dienophile. The double mutant S105A/I189A performs quite well for two of three dienophiles. Based on binding constants and NAC energies obtained from MD simulations combined with activation energies from DFT computations, relative catalytic rates (v(cat)/v(uncat)) of up to 103 are predicted. PMID- 20574697 TI - Management for males whose female partners are diagnosed with genital chlamydial infection. AB - The purpose of this study was to investigate the infection rate of asymptomatic men whose female sexual partners were diagnosed as having genital chlamydial infection and discuss the management for them. The subjects were asymptomatic men whose female sexual partners were diagnosed with genital chlamydial infection at other obstetric and gynecological clinics. Microscopic findings of urinary sediment and the results of a nucleic acid amplification test of the first-voided urine specimen were retrospectively examined in those men who visited our clinics. A total of 267 men were included and analyzed. The infection rate for urinary Chlamydia trachomatis in asymptomatic men was 36.3% (97 of 267). In the analysis of urinary sediment, 35 of the 267 (13.1%) had pyuria and 82.9% (29 of 35) in the men with pyuria were positive for urinary C. trachomatis in. Even in men without pyuria, the urinary C. trachomatis-positive rate was 29.3% (68 of 232). When such men have pyuria in the clinic, prompt treatment is the appropriate approach. If the men are without pyuria, testing for urinary C. trachomatis should be performed. Prompt treatment before doing any clinical evaluation can be an option in couples with trouble. PMID- 20574698 TI - Dissolved and particulate metals in water from Sonora Coast: a pristine zone of Gulf of California: metals in water from Sonora Coast. AB - The purpose of this study was to investigate the distribution of metals (Cd, Pb, Hg, Cu, Fe, Mn, and Zn) in dissolved and particulate fractions in seawater from Bacochibampo Bay, Northern part of Mexico. Water samples were collected from November 2004 to October 2005. Metal analysis was done by graphite furnace atomic absorption spectroscopy. Results indicated highest concentrations of dissolved Cd and Zn in the sites localized at the mouth and center of the bay. During summer and spring, the highest levels of Cd, Mn, and Fe were detected, Zn in fall, and Pb and Cu in winter and spring. Mercury was the only metal that was not found in this fraction. In particulate fraction, Fe, Hg, and Mn were the most abundant elements in all the sampling sites, followed by Zn, Cu, Pb, and Cd. The highest levels of the majority of the metals were observed in the coastline, suggesting a continental and/or urban source for these chemicals. The highest level of Cd was detected during the summer and the rest of the metals in the fall. Statistically significant correlations were observed between dissolved and particulate forms of Pb:Mn, Cu:Fe, and Cu:Mn. The mean partition coefficient values were as follows: Fe>Mn>Cu>Pb>Cd>Zn. All dissolved metal concentrations found, except Pb, were lower than EPA-recommended water quality values. The levels of dissolved metals in this study reveal low bioavailability and toxic potential. However, further toxicological and sediment chemistry studies in this area are needed for a full risk assessment. PMID- 20574699 TI - 64-Slice CT urography: 30 months of clinical experience. AB - PURPOSE: This study sought to assess the diagnostic accuracy of 64-slice computed tomography urography (CTU) in evaluation of the urinary tract. MATERIALS AND METHODS: A total of 322 CTU procedures were carried out in 317 consecutive patients (mean age 64.4 years). The findings were compared with previous and subsequent patient workup considering both laboratory and imaging studies, such as urine cytology, abdominal ultrasound and CT, cystoscopy, retrograde pyelography, surgery and pathology. RESULTS: Out of 322 CTU examinations, 169 showed significant urinary tract changes, whereas 153 revealed no urinary disease, in good agreement with the follow-up. In particular, in bladder evaluation, for which we have a direct comparison with cystoscopy in 125 patients, we calculated a CTU sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 85%, 94%, 92%, 89% and 90%, respectively. CONCLUSIONS: CTU was accurate for urinary tract evaluation, but it cannot replace cystoscopy in patients in whom a malignant bladder disease is suspected. PMID- 20574700 TI - Low dose CT of the heart: a quantum leap into a new era of cardiovascular imaging. AB - In 10 years, computed tomography coronary angiography (CTCA) has shifted from an investigational tool to clinical reality. Even though CT technologies are very advanced and widely available, a large body of evidence supporting the clinical role of CTCA is missing. The reason is that the speed of technological development has outpaced the ability of the scientific community to demonstrate the clinical utility of the technique. In addition, with each new CT generation, there is a further broadening of actual and potential applications. In this review we examine the state of the art on CTCA. In particular, we focus on issues concerning technological development, radiation dose, implementation, training and organisation. PMID- 20574702 TI - Utility of second-look ultrasound in the management of incidental enhancing lesions detected by breast MR imaging. AB - PURPOSE: To assess the utility of second-look ultrasound (US) for identifying and characterising incidental enhancing lesions detected by breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: From among 655 consecutive breast MRI studies, 62 lesions (MRI visible, nonpalpable, occult at first-look US and mammography) were recommended for second-look US. MRI enhancement of lesions was mass-like in 59 cases (95%) and non-mass-like in three (5%). Forty-two lesions (68%) were <=10 mm; only three lesions (5%) were >20 mm. Of all lesions, the Breast Imaging Reporting and Data System (BI-RADS) MRI category was highly suggestive of malignancy in six cases (10%), suspicious abnormality in 33 (53%) and probably benign in 23 (37%). The correlation between MRI lesion appearance, lesion size, histopathology findings and detection rate at second-look US were analysed. The reference standard was histopathology and/or follow-up (range 18-24 months). Statistical analysis was performed with the Fisher exact test. RESULTS: Second-look US identified 44 out of 62 (71%) lesions depicted at MRI. The detection rate at second-look US was higher for mass-like MRI lesions (75%) than non-mass-like lesions (0%), for lesion size >10mm (90%) and for BI-RADS 4 lesions (88%). Second-look US-guided biopsy detected 12 out of 17 (71%) malignant lesions. There was no correlation between the likelihood of carcinoma and the presence of a sonographic correlate. CONCLUSIONS: Second-look US is a reliable problem-solving tool in identifying and characterising most incidental MRI findings. It contributes to accurately selecting the cases in which MRI-guided biopsy is required. PMID- 20574701 TI - Multidetector computed tomography in the diagnosis and management of renal trauma. AB - Renal injuries fall within the broad and complex subject of retroperitoneal trauma. Although their computed tomography (CT) features have been known for a while, the timing, diagnostic approach and management are still debated. In addition, some areas of uncertainty remain regarding timing, indications and imaging modalities to be used in the follow-up of these patients. The purpose of this paper is to review the impact of CT on the management of renal trauma, stressing the importance of this technique and the role of the radiologist in the timing of decisions. Finally, we discuss the diagnostic approach to the follow-up of renal trauma. PMID- 20574703 TI - Assessment of liver metastases from colorectal adenocarcinoma following chemotherapy: SPIO-MRI versus FDG-PET/CT. AB - PURPOSE: This study compared superparamagnetic iron-oxide-enhanced magnetic resonance imaging (SPIO-MRI) and combined fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy. MATERIALS AND METHODS: Nineteen patients were included in this retrospective study. SPIO-MRI and PET/CT results were compared with surgery, intraoperative ultrasound and pathology results in 11 patients and with the follow-up in eight patients. RESULTS: SPIO MRI and PET/CT identified 125 and 71 metastases, respectively. False negative lesions were 11 for SPIO-MRI and 65 for PET/CT. In the whole study population, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 92% and 52% (p<0.001) and the per-segment analysis a sensitivity of 99% and 79% (p<0.001), respectively. In patients who underwent surgery, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 85% and 58% (p<0.05) and the per-segment analysis a sensitivity of 97% and 63% (p<0.05), respectively. In patients who underwent follow-up, the per-lesion analysis of SPIO-MRI and PET/CT showed a sensitivity of 97% and 47% (p<0.001) and the per-segment analysis a sensitivity of 100% and 63% (p<0.007), respectively. For lesions >=15 and <30 mm and for lesions <15 mm, SPIO-MRI demonstrated a higher sensitivity than PET/CT (p<0.001). CONCLUSIONS: SPIO-MRI appears superior to PET/CT in evaluating liver metastases from colorectal adenocarcinoma following chemotherapy. PMID- 20574704 TI - CT-guided needle biopsy performed with modified coaxial technique in the diagnosis of malignant lymphomas. AB - PURPOSE: The aim of was study was to evaluate the accuracy of computed tomography (CT)-guided core needle biopsy (CNB) performed by modified coaxial technique as an alternative tool to surgical biopsy in patients with suspected malignant lymphoma. MATERIALS AND METHODS: Between May 2005 and December 2008, 67 CT-guided CNB of deep lesions were performed on 64 patients with suspected malignant lymphoma. In 19 out of 64 patients (29.7%), recurrent lymphoma was suspected. A modified coaxial technique was used in all cases, and multiple samples were obtained for histological and immunohistochemical studies. RESULTS: A diagnosis of malignant lymphomas with specification of subtype according to the World Health Organization (WHO) classification was established in 41/67 cases. Other malignant neoplasms were found in 13/67, lymphoma without subtype specification was diagnosed in 7/67, whereas no conclusive diagnosis could be established in 6/67 cases. Overall diagnostic accuracy was 80.1%. In patients with a final diagnosis of malignant lymphoma, accuracy was 75.9%. No complications occurred. CONCLUSIONS: Percutaneous CT-guided CNB is a safe, effective and reliable tool in the management of lymphomas in patients without superficial lymphadenopathy and can be considered an alternative approach to surgical sampling. The modified coaxial technique represents an effective tool that has a good diagnostic accuracy value with a low complication rate. PMID- 20574705 TI - Contrast-enhanced MRI and PET-CT in the evaluation of patients with suspected local recurrence of rectal carcinoma. AB - PURPOSE: This study aimed to evaluate the role of contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET CT) in the assessment of local recurrence of rectal cancer. MATERIALS AND METHODS: Among 200 patients scheduled for CT follow-up, 60 (48 low risk; 12 high risk) were selected due to CT findings suspicious for or suggestive of local recurrence. Patients underwent contrast-enhanced MRI and PET-CT within 2 weeks. Biopsy was considered the gold standard in 39 cases and follow-up at 6 and 12 months in the remaining 21. RESULTS: Local recurrence was confirmed by histology in 15 cases (7 low risk; 8 high risk) and was excluded in 21 cases by long-term follow-up and in 24 by histology. Sensitivity, specificity, positive and negative predictive value and accuracy were 86.7%, 68.9%, 48.1%, 93.9% and 73.3% for contrast-enhanced MRI and 93.3%, 68.9%, 50%, 96.9% and 75% for PET-CT. CONCLUSIONS: Contrast-enhanced MRI and PET-CT can help in the detection of local recurrence of rectal cancer, even though their roles in early detection remains debatable, as the value of these techniques in current surveillance protocols is still to be defined. PMID- 20574706 TI - Prevalence of extravascular collateral findings during 64-slice CT angiography of the abdominal aorta and lower limbs. AB - PURPOSE: The aim of this study was to assess the prevalence of extravascular collateral findings during 64-slice CT angiography of the abdominal aorta (AA CTA) and lower limbs (LL-CTA). MATERIALS AND METHODS: The images of 536 AA-CTA and LL-CTA examinations performed for suspected aortic and peripheral vascular disease in 500 patients were retrospectively reviewed. Two radiologists evaluated the 5-mm axial images independently using appropriate window settings for the area under investigation. Collateral findings were divided according to their clinical significance into significant, nonsignificant and meriting further investigation. RESULTS: No collateral findings were identified in 97/500 patients (19.4%). In the remaining patients, 821 collateral findings were detected, of which 43 (5.24%) were classified as significant, 135 (16.44%) as meriting further investigation and 643 (78.32%) as nonsignificant. The findings indicative of the presence of a malignant lesion totalled 36 (4.5%). CONCLUSIONS: AA-CTA and LL-CTA demonstrate a nonnegligible prevalence of collateral findings, many of them major. It therefore appears that the evaluation should focus not only on the image reconstructions to identify vascular disease, but also on the native axial images to detect incidental findings. PMID- 20574707 TI - Evaluation of a method of computer-aided detection (CAD) of pulmonary nodules with computed tomography. AB - PURPOSE: The authors sought to compare the sensitivity and reading time obtained using computer-aided detection (CAD) software as second reader (SR) or concurrent reader (CR) in the identification of pulmonary nodules. MATERIALS AND METHODS: Unenhanced CT scans of 100 consecutive cancer patients were retrospectively reviewed by four readers to identify all solid, noncalcified pulmonary nodules ranging from 3 to 30 mm in diameter. The sensitivity and reading time of each reader and of CAD alone were calculated at 3-mm and 5-mm thresholds with respect to the reference standard, consisting of a consensus reading by the four radiologists involved in the study. The McNemar test was used to compare the sensitivities obtained by reading without CAD (readers 1 and 2), with CAD as SR (readers 1 and 2 with a 2-month delay), and with CAD as CR (readers 3 and 4). The paired Student's t test was used to compare reading times. A value of p<0.05 was considered statistically significant. RESULTS: A total of 258 and 224 nodules were identified at 3-mm and 5-mm thresholds, respectively. The sensitivity of CAD alone was 62.79% and 67.41% at the 3-mm and 5-mm threshold values respectively, with 4.15 and 2.96 false-positive findings per examination. CAD as SR produced a significant increase in sensitivity (p<0.001) in nodule detection with respect to reading without CAD both at 3 mm (12.01%) and 5 mm (10.04%); the average increase in sensitivity obtained when comparing CAD as SR to CAD as CR was statistically significant (p<0.025) both at the 3-mm (5.35%) and 5-mm (4.68%) thresholds. CAD as CR produced a nonsignificant increase in sensitivity compared with reading without CAD (p>0.05). Mean reading time using CAD as SR (330 s) was significantly longer than reading without CAD (135 s, p<0.001) and reading with CAD as CR (195 s, p<0.025). CONCLUSIONS: The use of CAD as CR, without any significant increase in reading time, produces no significant increase in sensitivity in pulmonary nodule detection when compared with reading without CAD (p>0.05); CAD as SR, at the cost of longer reading times, increases sensitivity when compared with reading without CAD (p<0.001) or with CAD as CR (p<0.025). PMID- 20574708 TI - Lower-lobe shrinkage relative to total lung volume in collagen vascular diseases. AB - PURPOSE: It has been reported that the prognosis differs between patients who have collagen vascular diseaseassociated interstitial pneumonia (CVD-IP) and those with idiopathic IP (IIP). In this study, chest computed tomography (CT) findings were compared between patients with CVD-IP and IIP. MATERIALS AND METHODS: A retrospective analysis was performed of 47 consecutive patients (23 with CVD-IP and 24 with IIP). The lower-lobe volume (LLV), total lung volume (TLV), and their ratio (LLV/TLV) were determined by volumetry using three dimensional computed tomography (CT). RESULTS: There was no significant difference of the LLV/TLV ratio between the CVD-IP and IIP groups. However, the LLV/TLV ratio was <0.33 in 9/23 patients with CVD-IP versus 2/24 patients with IIP, and there was a significant difference in the percentage of patients with a ratio<0.33 between the CVD-IP and IIP groups (p = 0.01). The LLV/TLV ratio was not influenced by the severity of lung disease. CONCLUSIONS: Measuring the LLV/TLV ratio by threedimensional CT can help distinguish between CVD-IP and IIP at initial diagnosis, especially in patients with CVD-IP who have pulmonary involvement before other organ diseases and symptoms caused by CVD. PMID- 20574709 TI - Chromatin modifications that support acetylcholine receptor gene activation are established during muscle cell determination and differentiation. AB - Localization of acetylcholine receptors (AChRs) to the postsynaptic region of muscle is mediated in part by transcriptional mechanisms. An important way of regulating transcription is through targeting histone modifications on chromatin to distinct gene loci. Using chromatin immunoprecipitation, we examined the developmental regulation of certain histone modifications at the AChR epsilon subunit locus, including methylations at lysine residues K4 and K27 and acetylations at K9 and K14. We modeled various stages of muscle development in cell culture, including pre-determined cells, committed but undifferentiated myoblasts, and differentiated myotubes, and modeled synaptic myotube nuclei by stimulating myotubes with neuregulin (NRG) 1. We found that a pattern of histone modifications associated with transcriptional activation is targeted to the AChR epsilon subunit locus in myotubes prior to stimulation with NRG1 and does not change upon addition of NRG1. Instead, we found that during muscle cell determination and differentiation, specific histone modifications are targeted to the AChR epsilon subunit locus. Within the gene, at K4, dimethylation is induced during muscle cell determination, while trimethylation is induced during differentiation. At K27, loss of trimethylation and appearance of monomethylation occurs during determination and differentiation. In addition, in a region upstream of the gene, K4 di- and trimethylation, and K9/14 acetylation are induced in a distinct developmental pattern, which may reflect a functional regulatory element. These results suggest synaptic signaling does not directly target histone modifications but rather the histone modification pattern necessary for transcriptional activation is previously established in a series of steps during muscle development. PMID- 20574710 TI - Targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell. AB - Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Studies in recent years indicated that survivin(sur) expression was associated with the biological behaviors of gastric carcinoma. In the present study, targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell were investigated, the recombinant pSCT vector containing CD and TK genes driven by sur promoter was constructed and transfected into SGC-7901 cells. After adding the CCV and 5-FC, the effects of double suicide genes on cell growth, cell cycle and proliferation were determined by MTT assay and flow cytometry (FCM). The results showed that sur promoter could specifically drive the expression of double CD/TK gene in SGC 7901 cells, whereas not in the normal GES-1 cell. After using CCV and 5-FC, the growth of SGC-7901 cells was inhibited. G1 phase proportion was significantly higher in SGC-7901 cells transfected with double suicide genes than the untransfected cells. These results suggest that CD and TK double suicide genes driven by sur promoter could provide a new approach for enhancing selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma. PMID- 20574711 TI - On the origin of Solanum nigrum: can networks help? AB - Black nightshades are a group of species best known for their 'poisonous' or noxious weedy reputation. It is not so well known that species of this group serve as emerging food source in many countries worldwide especially in the African continent. Despite the fact that the section has recently been studied extensively, taxonomy is still unsettled and debated because of inter- and intraspecific hybridization, phenotypic plasticity and polyploidization. In this study we analyze the genetic relationships among diploid, tetraploid and hexaploid species of sect. Solanum, which have possibly taken part in the formation of Solanum nigrum, utilizing multi-locus (SCoT, ISSR) markers combined with chloroplast trnL-F sequence data and morphological characters. We scored 51 morphological characters united with SCoT (171), ISSR (224) and trnL-F (1042), for simultaneous analysis of 49 terminals and 1488 characters. The topology of the tree is concordant with the results of the network analysis. In the phylogenetic networks, all the accessions of the diploid species shared a split with all of the polyploid species. This reflected a high portion of shared ISSR and SCoT bands between diploids and polyploids. In addition, a strong split divided the diploid species. The history of S. nigrum might be reticulate with hybrid speciation playing an important rule. Genetically differentiated diploids in few combinations have created a series of genetically distinct polyploid populations. The insufficient isolation that permitted further recombination between ancient polyploids and diploids have resulted in high level of genotypic and phenotypic polymorphism. This high level of novel genomic variability obviously enabled species to succeed in their new environment. PMID- 20574712 TI - Species delineation in Pampus (Perciformes) and the phylogenetic status of the Stromateoidei based on mitogenomics. AB - Recent studies on the mitochondrial genome have suggested that the duplications of tRNA and tandem repeats in the control region are important changes that are related to species diversity. This paper reports the study of mitogenomes from five Pampus (Perciformes, Stromateidae) species with very similar morphology. A duplicated tRNA(Met) gene in the tRNA-IQM region is present in Pampus sp. and P. punctatissimus. In the conserved sequence blocks of the control region, a duplicated CSB3 and promoter are found in Pampus sp. but are absent in P. minor. Moreover, a duplicated TAS is found in P. punctatissimus and P. chinensis. Based on the complete mitogenome sequence of Pampus sp., the first sequence reported from Stromateidae and the longest (17,694 bp) among the Perciformes mitogenomes, we conducted phylogenetic analysis to show that Stromateoidei and Scombroidei are more closely related to each other than to other Perciformes suborders. However, we reject the reciprocal monophyly of these two suborders. PMID- 20574713 TI - Regulation of expression of antioxidant enzymes by vitamin E and curcumin in L thyroxine-induced oxidative stress in rat renal cortex. AB - The present study investigates the antioxidative effects of vitamin E and curcumin against L-thyroxine (T(4))-induced oxidative stress in renal cortex of adult male rats. Rats were made hyperthyroid by administration of L-thyroxine (0.0012%) in their drinking water for 30 days. Vitamin E (200 mg/kg body weight/day) and curcumin (30 mg/kg body weight/day) were supplemented singly or in combination orally for 30 days along with L-thyroxine treatment. The elevated level of oxidative stress parameters (lipid peroxidation and protein carbonylation) and decline level of small antioxidant molecules (reduced glutathione and ascorbic acid) in renal cortex of T(4)-treated rats were restored back by supplementation of vitamin E or/and curcumin. Increased superoxide dismutase and catalase activities in kidney cortex of T(4)-treated rats were ameliorated in response to vitamin E or/and curcumin treatment. The elevated translated product of Cu/Zn-SOD, Mn-SOD and catalase in T(4)-treated rats were differentially reduced by the administration of vitamin E and curcumin independently or in combination. Cu/Zn-SOD expression was ameliorated by both vitamin E and curcumin independently or in combination, whereas Mn-SOD expression was ameliorated by the supplementation of vitamin E or curcumin independently. However, the expression of catalase was alleviated by only supplementation of vitamin E to T(4)-treated rats. The results suggest that both vitamin E and curcumin may play an important role in protecting T(4)-induced oxidative stress in rat renal cortex by differentially modulating the activities of antioxidant enzymes and oxidative stress parameters. PMID- 20574714 TI - Novel RBPJ transcripts identified in human amniotic fluid cells. AB - The NOTCH signaling pathway plays important roles in stem cell maintenance, cell fate determination and differentiation during development. Following ligand binding, the cleaved NOTCH intracellular domain (NICD) interacts directly with the recombinant signal binding protein for immunoglobulin kappa J region (RBPJ) transcription factor and the resulting complex targets gene expression in the nucleus. To date, four human RBPJ isoforms have been described in Entrez Gene, varying in the first 5'coding exons. Using an improved protocol, we were able to further identify all four known and five novel RBPJ transcript variants in human amniotic fluid (AF) cells, a cell type known for its stem cell characteristics. In addition, we used human embryonal carcinoma (EC) NTera2/D1 (NT2) cells and NT2 derived neuron and astrocytes to compare the expression pattern of RBPJ transcripts. Further examination of RBPJ transcripts showed that the novel splice variants contain open reading frames in-frame with the known isoforms, suggesting that they can putatively generate similar function proteins. All known and novel RBPJ transcripts contain the putative nuclear localization signal (NLS), an important component of RBPJ-mediated gene regulation. PMID- 20574715 TI - Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylketonuria shows a higher body fat percentage. AB - BACKGROUND: Phenylketonuria (PKU) causes irreversible central nervous system damage unless a phenylalanine (PHE) restricted diet with amino acid supplementation is maintained. To prevent growth retardation, a protein/amino acid intake beyond the recommended dietary protein allowance is mandatory. However, data regarding disease and/or diet related changes in body composition are inconclusive and retarded growth and/or adiposity is still reported. The BodPod whole body air-displacement plethysmography method is a fast, safe and accurate technique to measure body composition. AIM: To gain more insight into the body composition of children with PKU. METHODS: Patients diagnosed with PKU born between 1991 and 2001 were included. Patients were identified by neonatal screening and treated in our centre. Body composition was measured using the BodPod system (Life Measurement Incorporation(c)). Blood PHE values determined every 1-3 months in the year preceding BodPod analysis were collected. Patients were matched for gender and age with data of healthy control subjects. Independent samples t tests, Mann-Whitney and linear regression were used for statistical analysis. RESULTS: The mean body fat percentage in patients with PKU (n = 20) was significantly higher compared to healthy controls (n = 20) (25.2% vs 18.4%; p = 0.002), especially in girls above 11 years of age (30.1% vs 21.5%; p = 0.027). Body fat percentage increased with rising body weight in patients with PKU only (R = 0.693, p = 0.001), but did not correlate with mean blood PHE level (R = 0.079, p = 0.740). CONCLUSION: Our data show a higher body fat percentage in patients with PKU, especially in girls above 11 years of age. PMID- 20574716 TI - Diagnosis and high incidence of hyperornithinemia-hyperammonemia homocitrullinemia (HHH) syndrome in northern Saskatchewan. AB - Mutations in the SLC25A15 gene, encoding the human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition. HHH syndrome has been detected in several small, isolated communities in northern Saskatchewan (SK). To determine the incidence of HHH syndrome in these communities, a PCR method was set up to detect F188Delta, the common French Canadian mutation. Neonatal blood spots collected from all newborns from the high risk area were genotyped for the F188Delta mutation for seven consecutive years. Using DNA analysis, we estimated that the heterozygote frequency for the mutant allele for HHH syndrome to be about 1 in 19 individuals, predicting one affected child with HHH syndrome for approximately every 1,500 individuals (1 in 1,550 live births; 1 child every 12 years) in this isolated population. The frequency for the mutant allele for HHH syndrome in this isolated community is probably the highest in the world for this rare disorder. We determined that ornithine levels, by tandem mass spectrometry, were not abnormal in newborns with F188Delta mutation, carriers and normals. Ornithine rises to abnormally high levels at some time after birth well past the time that the newborn screening blood spot is collected. The timing or the reasons for the delayed rise of ornithine in affected children with HHH syndrome have not been determined. Newborn screening for HHH Syndrome in this high risk population is only possible by detection of the mutant allele using DNA analysis. PMID- 20574718 TI - Deltoid contracture mimicking shoulder dislocation in a 7-year-old boy. AB - Contracture of the deltoid muscle, a relatively uncommon disorder in children, can be caused by repeated intramuscular injection, trauma, or congenital disease. The typical clinical manifestations of deltoid contracture (i.e., a palpable fibrous cord within the deltoid muscle, abduction contracture of the shoulder, winged scapula, and skin dimpling over the fibrous bands), however, may be atypical or even lacking, thus, leading to misdiagnosis. The procedure going from misdiagnosis to recognition of the correct diagnosis is reviewed in a 7-year-old boy with deltoid contracture. PMID- 20574717 TI - Trichophyton erinacei infection from a hedgehog: a case report from Taiwan. AB - Trichophyton erinacei is a fungus affecting hedgehogs. As these animals have become popular as exotic pets, human infections with this organism have been documented in many countries. In Taiwan, a 36-year-old woman developed tinea lesions at multiple sites after carrying a sick hedgehog. The animal subsequently lost its quills and died. On culture of the patient's skin scrapings, the pathogen was identified mycologically as Trichophyton erinacei, which was confirmed by sequencing of the internal transcribed spacers of the fungal nuclear ribosomal DNA. The same fungus was isolated from the sawdust bed previously used by the diseased hedgehog. A careful contact history is important for identifying this emerging zoonosis. PMID- 20574719 TI - [Vertebroplasty: an update: value of percutaneous cement augmentation after randomized, placebo-controlled trials]. AB - Percutaneous cement augmentation (kyphoplasty and vertebroplasty) has become established as a procedure for treatment of painful osteoporotic vertebral fractures and certain neoplastic changes. The injection of cement ensures rapid stabilization of the vertebra and prevents further sintering. This also results in pain improvement. Nonetheless, based on two placebo-controlled trials, this treatment approach has been called into question. However, these studies did not take the technical aspects of the treatment into consideration, and it appears probable that the amount of filler material chosen was too small so that the treatment group also received placebo. Furthermore, it is likely that mostly older fractures were treated so that the effect can no longer be expected to be as pronounced. A randomized, controlled trial comparing kyphoplasty to conservative management provided good evidence that cement augmentation is of benefit within the first year. Newer procedures for kyphoplasty are very promising, but their clinical significance still needs verification. PMID- 20574720 TI - Novel parvovirus sublineage in the family of Parvoviridae. AB - Parvoviridae, which are classified into two subfamilies Parvovirinae and Densovirinae, can infect both vertebrate and insects and are related to a wide range of diseases in insects, animals, and humans. In this report, several new parvoviruses were identified in swine sera collected in southeastern China. The sequence analyses showed that the parvoviruses detected in southeastern China formed a distinct sublineage within the subfamily Parvovirinae. Based on these results, we propose a novel parvovirus sublineage, Cnvirus, to describe these parvoviruses. PMID- 20574721 TI - Improved detection of fluorescently labeled microspheres and vessel architecture with an imaging cryomicrotome. AB - Due to spectral overlap, the number of fluorescent labels for imaging cryomicrotome detection was limited to 4. The aim of this study was to increase the separation of fluorescent labels. In the new imaging cryomicrotome, the sample is cut in slices of 40 microm. Six images are taken for each cutting plane. Correction for spectral overlap is based on linear combinations of fluorescent images. Locations of microspheres are determined by using the system point spread function. Five differently colored microspheres were injected in vivo distributed over two major coronaries, the left anterior descending and left circumflex artery. Under absence of collateral flow, microspheres outside of target perfusion territories were not found and the procedure did not generate false positive detection when spectral overlap was relevant. In silico-generated microspheres were used to test the effect of background image, transparency correction, and color separation. The percentage of microspheres undetected was 2.3 +/- 0.8% in the presence and 1.5 +/- 0.4% in the absence of background structures with a density of 900 microspheres per color per cm(3). The image analysis method presented here, allows for an increased number of experimental conditions that can be investigated in studies of regional myocardial perfusion. PMID- 20574722 TI - Enhancement of the ultrasound images by modified anisotropic diffusion method. AB - Speckle is a primary factor which degrades the contrast resolution and masks the meaningful texture information present in an ultrasound image. Its presence severely hampers the interpretation and analysis of ultrasound images. When speckle reduction technique is applied for visual enhancement of ultrasound images, it is to be kept in mind that blurring associated with speckle reduction should be less and fine details are properly enhanced. With these points in consideration, the modified speckle reduction anisotropic diffusion (MSRAD) method is proposed in the present study to improve the visual quality of the ultrasound images. In the proposed MSRAD method, the four neighboring pixel template in speckle reduction anisotropic diffusion (SRAD) method of Yu and Acton (IEEE Trans Image Process 11:1260-1270, 2002) have been replaced by a new template of larger number of neighboring pixels to calculate the diffusion term. To enhance visual quality of ultrasound images, nonquadratic regularization (Yu and Yadegar, Proceedings of the IEEE international conference on image processing, 2006) is incorporated with MSRAD method and accordingly changes in parameter settings have been made. The performance of MSRAD method was evaluated using clinical ultrasound images, interpretation by the medical experts and results of MSRAD method by subjective and objective criteria. PMID- 20574723 TI - Magnetic biosensor technologies for medical applications: a review. AB - In this review we discuss conventional methods of performing biological assays and molecular identification and highlight their advantages and limitations. An alternative approach based on magnetic nanotechnology is then presented. Firstly, magnetic carriers are introduced and their biocompatibility and functionalisation discussed, with spotlights on functionalisation via self assembled monolayers and on methods of reducing nonspecific binding. In addition an introduction is provided to the basic physical concepts behind the various types of sensors used to detect magnetic labels. Finally, progress in the field of magnetic biosensors and the outlook for the future are discussed. PMID- 20574724 TI - Automatic video detection of body movement during sleep based on optical flow in pediatric patients with epilepsy. AB - The aim of our work is to investigate whether the optical flow algorithm applied to video recordings can be used to detect movement during sleep in pediatric patients with epilepsy. The optical flow algorithm allocates intensities to pixels proportional to their involvement in movement of an object. The average of a percentage of the highest movement vectors was plotted as a function of time (R(t)). The used dataset contains video data acquired at the University Hospital of Leuven consisting of normal sleep movement and seizure movement. We investigated R(t), to make a distinction between movement and non-movement. We used the acquisition parameters (320 x 240 at 12.5 fps), derived from a previous study (Cuppens et al., Proceedings of the 4th European congress of the international federation for medical and biological engineering (MBEC 2008), ECIFBME 2008, Antwerp, Belgium, IFMBE Proceedings, vol 22, pp 784-789, 2008). Two experiments were concluded, one with global thresholds of R(t) in all datasets and one with a variable threshold in each dataset. The latter is obtained by inspecting a non-movement epoch and calculating the mean and standard deviations of R(t) over time. The variable threshold on R(t) was then obtained for each dataset by adding to the mean a fixed multiple of the standard deviation. Optimal thresholds were derived based on a three-fold cross-validation. The best result was achieved when using a variable threshold, which resulted in a sensitivity of one in all the test sets and a PPV of 1, 0.821, and 1, respectively, for the three test sets. PMID- 20574725 TI - Automated detection of obstructive sleep apnoea syndrome from oxygen saturation recordings using linear discriminant analysis. AB - Nocturnal polysomnography (PSG) is the gold-standard to diagnose obstructive sleep apnoea syndrome (OSAS). However, it is complex, expensive, and time consuming. We present an automatic OSAS detection algorithm based on classification of nocturnal oxygen saturation (SaO(2)) recordings. The algorithm makes use of spectral and nonlinear analysis for feature extraction, principal component analysis (PCA) for preprocessing and linear discriminant analysis (LDA) for classification. We conducted a study to characterize and prospectively validate our OSAS detection algorithm. The population under study was composed of subjects suspected of suffering from OSAS. A total of 214 SaO(2) signals were available. These signals were randomly divided into a training set (85 signals) and a test set (129 signals) to prospectively validate the proposed method. The OSAS detection algorithm achieved a diagnostic accuracy of 93.02% (97.00% sensitivity and 79.31% specificity) on the test set. It outperformed other alternative implementations that either use spectral and nonlinear features separately or are based on logistic regression (LR). The proposed method could be a useful tool to assist in early OSAS diagnosis, contributing to overcome the difficulties of conventional PSG. PMID- 20574726 TI - Evolution of linear mitochondrial DNA in three known lineages of Polytomella. AB - Although DNA sequences of linear mitochondrial genomes are available for a wide variety of species, sequence and conformational data from the extreme ends of these molecules (i.e., the telomeres) are limited. Data on the telomeres is important because it can provide insights into how linear genomes overcome the end-replication problem. This study explores the evolution of linear mitochondrial DNAs (mtDNAs) in the green-algal genus Polytomella (Chlorophyceae, Chlorophyta), the members of which are non-photosynthetic. Earlier works analyzed the linear and linear-fragmented mitochondrial genomes of Polytomella capuana and Polytomella parva. Here we present the mtDNA sequence for Polytomella strain SAG 63-10 [also known as Polytomella piriformis (Pringsheim 1963)], which is the only known representative of a mostly unexplored Polytomella lineage. We show that the P. piriformis mtDNA is made up of two linear fragments of 13 and 3 kb. The telomeric sequences of the large and small fragments are terminally inverted, and appear to end in vitro with either closed (hairpin-loop) or open (nicked-loop) structures as also shown here for P. parva and shown earlier for P. capuana. The structure of the P. piriformis mtDNA is more similar to that of P. parva, which is also fragmented, than to that of P. capuana, which is contained in a single chromosome. Phylogenetic analyses reveal high substitution rates in the mtDNA of all three Polytomella species relative to other chlamydomonadalean algae. These elevated rates could be the result of a greater number of vegetative cell divisions and/or small population sizes in Polytomella species as compared with other chlamydomonadalean algae. PMID- 20574728 TI - Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance. AB - Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress. PMID- 20574727 TI - Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases. AB - PURPOSE: Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. METHODS: Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). RESULTS: By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15-0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083-0.86, P = 0.026) than 5-FU/LV-based. CONCLUSIONS: Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy. PMID- 20574729 TI - Three new aromatic glycosides from the ripe fruit of cherry tomato. AB - Three new aromatic glycosides were isolated from the ripe fruit of cherry tomato [Lycopersicon esculentum var. cerasiforme (Dunal) Alef. (Solanaceae)] along with six known aromatic glycosides and one known steroidal alkaloid glycoside. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence. PMID- 20574730 TI - Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer? AB - BACKGROUND: Patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have favorable disease-free survival rates. A few studies have suggested that lymphovascular invasion degree may play an important role in predicting pCR. This study aims to confirm the role of lymphatic invasion degree in predicting pCR in breast cancer patients after NAC. METHODS: We retrospectively analyzed 120 patients treated with NAC and surgery. The following pathological features were evaluated on surgical specimens after NAC: histological grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), lymphovascular invasion degree, intratumoral necrosis positivity, and axillary lymph node positivity. RESULTS: pCR and marked response were achieved in 12% (14/120) and 35% (42/120), respectively, of 120 breast cancers in 120 women. Breast cancers with pCR or marked response were classified as chemosensitive. The remaining 64 breast cancers (53%) were classified as chemoresistant. Severe lymphovascular invasion (P = .003), large tumor size (P = .029), ER positivity (P = .001), and PR positivity (P = .006) were significantly associated with chemoresistant breast cancer. Invasive ductal carcinoma (P = .028) and HER-2 positivity (P < .0001) were significantly associated with chemosensitive breast cancer. On multivariate analysis, HER-2 positivity (P < .0001), invasive ductal carcinoma (P = .047), and marked/moderate lymphovascular invasion (P = .023) were the three factors that remained statistically significant in the model to predict histological therapeutic effect. CONCLUSION: Lymphovascular invasion degree is one of the important factors to predict NAC efficacy for breast cancer. PMID- 20574731 TI - Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer's perspective. AB - No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no study in cost of MDS exists in Germany, the objective of this study was to assess and analyze costs of transfusion-dependent low/intermediate-1-risk MDS in Germany from a payers' perspective. From seven centers, 116 low/intermediate-1-risk transfusion dependent MDS patients with and without isolated 5q-deletion were identified. Claims data and patient records of the previous 5 years were used to collect health care utilization data retrospectively. Publicly available tariff books and remuneration schemes were applied to evaluate mean costs per year in Euro with 2007 as base year. The annual cost of MDS patients was estimated at 14,883. Subgroup analyses showed differences in patient's characteristics and outcomes among patients treated at a hospital-based vs. an office-based setting. Patients treated at the hospital-based registry show higher cost, whereas the reasons for that still need to be detected. Overall, per annum direct costs range from 12,543 (SD 12,967) to 24,957 (SD 36,399) in different subgroups of patients. In both groups, patients with 5q-deletion use more medication than those without deletion. Mean costs for medication in the office-based setting are 5,902 for patients with isolated 5q-deletion vs. 3,932 for patients with no deletion, respectively. MDS leads to a high health care utilization and resulting costs for the health care system which requires a detailed analysis of underlying services. PMID- 20574732 TI - Hemoglobin O(Indonesia) in India: a rare observation. PMID- 20574733 TI - Outcome of attempted Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia. AB - There are limited data on outcomes of Hickman catheter salvage associated with Staphylococcus aureus bacteremia (SAB) in neutropenic cancer patients. We evaluated the outcome of attempted Hickman catheter salvage in these patients who were not given antibiotic lock therapy. Outcomes were retrospectively analyzed in all neutropenic cancer patients with Hickman catheter-related SAB over a 12-year period (56 episodes in 54 patients). Salvage attempts were defined as cases where the catheter was still in place 3 days after initial bacteremia. Salvage attempts were considered successful if catheter was still in place 12 weeks later without recurrent SAB or death. Of the 56 episodes, catheters were immediately removed in eight (14%), and catheter salvage was attempted in 48 (86%). Of these 48 episodes, attempted salvage was successful in 29 (60%) and failed in 14 (29%). Outcome of attempted salvage was indeterminate in five (11%) episodes. In univariate analysis, presence of external signs of catheter infection (p = 0.03), positive follow-up blood culture (p = 0.03), and methicillin resistance (p = 0.04) were significantly associated with catheter salvage failure. In multivariate analysis, presence of external signs of catheter infection (OR 12.0; p = 0.04) and methicillin resistance (OR 5.1; p = 0.04) were independently associated with catheter savage failure. In conclusion, attempted catheter salvage without antibiotic lock therapy was successful in 60% of the patients with Hickman catheter-related SAB. External signs of catheter infection and methicillin resistance were independent risk factors for catheter salvage failure. PMID- 20574734 TI - Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting. AB - Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (EliteTM XL, AscensiaTM ContourTM and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance. PMID- 20574735 TI - Endovascular coil embolization of very small intracranial aneurysms. AB - INTRODUCTION: Endovascular coil embolization of very small (maximum dome diameter <=3 mm) aneurysms is controversial because of a high risk for procedural rupture and technical difficulty. We report clinical and angiographic results of coil embolization of these aneurysms. METHODS: From August 2005 through July 2009, 43 very small aneurysms (23 ruptured, 20 unruptured) in 38 patients (12 males, 26 females; mean age, 53 years) were embolized with detachable coils. Of those 38 patients, 24 (63%) presented with subarachnoid hemorrhage (SAH) from a very small aneurysm (n = 23) or another aneurysm (n = 1). We assessed initial angiographic results, procedural complications, and clinical condition with initial Hunt and Hess grade (HH) and Glasgow outcome scale (GOS) at discharge. Follow-up results were evaluated with conventional angiography and/or magnetic resonance angiography (MRA). RESULTS: Initial aneurysmal occlusion was total in 16 (37%), subtotal in 22 (51%), and partial in five (12%) aneurysms. There were five incidents of thrombosis (12%) and one procedural rupture (2%), but there was no definite adverse effect on clinical outcome. Of 24 patients with SAH, ten patients (42%) were in poor condition (HH 3 or 4) at admission. Seventeen of 24 patients (71%) had good or excellent outcome (GOS >=4) at discharge. A 6-month or more follow-up angiography and/or MRA was available in 33 (11 total and 20 subtotal and 2 partial in initial occlusion) aneurysms (77%) in 28 patients and revealed stable occlusion in 20 aneurysms (61%), progressive total occlusion in 10 (30%), minor recanalization in 2 (6%), and major recanalization in 1 (3%). CONCLUSIONS: Coil embolization of very small aneurysms may be technically feasible with favorable clinical/angiographic outcomes and relatively low recanalization rate during 6 months or more follow-up period. PMID- 20574737 TI - William Markesbery, M.D.: some personal recollections. PMID- 20574736 TI - Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity. AB - Photoparoxysmal response (PPR) is characterized by abnormal visual sensitivity of the brain to photic stimulation. Frequently associated with idiopathic generalized epilepsies (IGEs), it might be an endophenotype for cortical excitability. Transient receptor potential cation (TRPC) channels are involved in the generation of epileptiform discharges, and TRPC4 constitutes the main TRPC channel in the central nervous system. The present study investigated an association of PPR with sequence variations of the TRPC4 gene. Thirty-five single nucleotide polymorphisms (SNP) within TRPC4 were genotyped in 273 PPR probands and 599 population controls. Association analyses were performed for the broad PPR endophenotype (PPR types I-IV; n = 273), a narrow model of affectedness (PPR types III and IV; n = 214) and PPR associated with IGE (PPR/IGE; n = 106) for each SNP and for corresponding haplotypes. Association was found between the intron 5 SNP rs10507456 and PPR/IGE both for single markers (P = 0.005) and haplotype level (P = 0.01). Three additional SNPs (rs1535775, rs10161932 and rs7338118) within the same haplotype block were associated with PPR/IGE at P < 0.05 (uncorrected) as well as two more markers (rs10507457, rs7329459) located in intron 3. Again, the corresponding haplotype also showed association with PPR/IGE. Results were not significant following correction for multiple comparisons by permutation analysis for single markers and Bonferroni-Holm for haplotypes. No association was found between variants in TRPC4 and other phenotypes. Our results showed a trend toward association of TRPC4 variants and PPR/IGE. Further studies including larger samples of photosensitive probands are required to clarify the relevance of TRPC4 for PPR and IGE. PMID- 20574738 TI - The role of surface charge and hydrophobicity in the attachment of Anoxybacillus flavithermus isolated from milk powder. AB - The aim of the present study was to investigate the attachment mechanisms that enable the thermophile Anoxybacillus flavithermus (B12) to attach to stainless steel surfaces. Passing a B12 culture through a column of stainless-steel chips, collecting the first cells to pass through, re-culturing, and repeating the process six times, resulted in the isolation of a mutant, labeled X7, with tenfold reduced ability to attach to stainless steel as well as a reduced ability to attach to plastic. A comparison of bacterial cell-surface properties indicated that X7 was less hydrophobic than its parental strain B12. Cell-surface charge measurements also suggest that X7 had a lower net-negative surface charge. Disruption of extracellular polysaccharides and DNA appeared to have no effect on the attachment process. Removal of surface proteins caused a reduction in attachment of both B12 and X7, suggesting surface protein involvement in attachment. PMID- 20574739 TI - [Cardiac effects of obstructive sleep apnea]. AB - Sleep disordered breathing, especially obstructive sleep apnea, are common in cardiovascular disease. Negative hemodynamic effects are mediated by nocturnal ischemia and intrathoracal pressure swings. Therefore "therapy resistant" arterial hypertension and congestive heart failure, as well as atrial fibrillation or sleep associated bradycardia are suggestive of sleep disordered breathing. Further on, clinical course of coronary artery disease seems to be influenced by nocturnal breathing disorders. Application of continuous positive airway pressure (CPAP) is effective in most of the patients and attenuates cardiodepressive hemodynamic effects of obstructive sleep apnea. PMID- 20574740 TI - Depressed skull fracture by a three-pin head holder: a case illustration. AB - BACKGROUND AND CASE REPORT: Many surgical procedures require a rigid immobilization of the patients' head, which is usually achieved by using a pin type head holder. We briefly illustrate the case of a 4-year-old girl who sustained a depressed skull fracture by penetration of a pin of the head holder. The fracture was noted at the end of the surgery performed for treatment of a cerebellar astrocytoma and was managed conservatively. DISCUSSION: Several factors seem to be involved in the production of this complication as are faulty application of the pins, excessive pin pressure, skull thinning, young patient's age, and pathological conditions that evolve with long-standing raised intracranial pressure. Prevention and management measures are briefly discussed. PMID- 20574741 TI - Comment to the paper "Surgical outcome of patients considered to have 'inoperable' tumors by specialized pediatric neurooncological multi-disciplinary teams". "Surgical outcome of patients considered to have 'inoperable' tumors by specialized pediatric neurooncological multi-disciplinary teams: should we caution against multidisciplinary decisions?". PMID- 20574742 TI - CO2 laser-assisted microsurgery for intracordal cysts: technique and results of 49 patients. AB - Microsurgery for intracordal cysts is a challenging procedure, because cysts are close to the vocal ligament and the risk of inducing a scar is high. In this retrospective study, our experience with the CO(2)-laser scanning system (Acublade((r))) is reported on 49 patients. There were 41% epidermoid cysts and 59% mucous retention cysts. A quarter of the patients presented with bilateral cystic lesions and 59% had a contralateral lesion other than a cyst. The cyst was removed after a minimicroflap. It was dissected away from the lamina propria and the epithelium. Collagen was injected intraoperatively if the glottal gap was considered important. The epithelium was redraped using Tissucol (Baxter, Vienna, Austria). The mean follow-up time was 160 days. We noted a statistically significant improvement in the grade of the dysphonia according to Hirano's perceptual scale (G pre = 2, G post = 1, p = 0.002); the Vocal Handicap Index (VHI pre = 51, VHI post = 28, p = 0.001) and the maximal phonation time in milliseconds (MPT pre = 11, 1 MPT post = 12.7, p = 0.033) in all the patients. In the professional voice subgroup (20/49 patients), there was a significant improvement in the frequency range (FR pre = 310 Hz, FR post = 434 Hz, p = 0.001). The CO(2)-laser scanning system is reliable in the treatment of intracordal cysts. PMID- 20574743 TI - Efficacy of topical halofuginone in myringotomy patency. AB - The objective of the study is to determine whether topical halofuginone (HF) application has an impact on prolonging the time for healing of myringotomy incision, and to investigate histopathologic effects of HF on tympanic membrane (TM) in rat model. Forty rats with normal eardrums were involved in this study. The study group and control group consisted of 30 and 10 rats, respectively. A posterior incision 1 mm in diameter was made on healthy eardrums of the rats. Following incision, gelfoam soaked with HF hydrobromide of 30 mg/dl was applied on the perforation in study group, whereas gelfoam soaked with isotonic saline was applied on the perforation in control group. On days 1, 3, 7, 10, 14, 18, 21, 24, 27, and 30, otoendoscopic evaluation of eardrums under general anesthesia was conducted and perforations were screened. A rat of each group was killed in control days and TMs were dissected to evaluate histopathological changes. The average times for patency of perforation in study and control groups were 21.43 and 7.50 days, respectively. The difference was found to be statistically significant (p < 0.05). Histopathological evaluation revealed that HF reduces hyalinisation and fibrosis in eardrum, when compared with the control group. In conclusion, HF significantly delays closure time of myringotomies in rat model. However, this delay may not be enough for recovery of otitis media with effusion. PMID- 20574744 TI - Genetic association of NALP1 with generalized vitiligo in Jordanian Arabs. AB - Generalized vitiligo is an autoimmune disorder characterized by patchy loss of pigmentation due to autoimmune destruction of melanocytes in the involved areas. Vitiligo is a polygenic, multifactorial disorder involving multiple genes and unknown environmental triggers. Recently, genetic variation in NALP1 (also called NLRP1), encoding a key regulator of the innate immune response, has been associated with generalized vitiligo in Caucasians of northern European origin. Here, we have investigated whether NALP1 is also associated with generalized vitiligo in Jordanian Arab patients. We genotyped 8 NALP1 single-nucleotide polymorphisms (SNPs) in 26 generalized vitiligo patients and 61 matched controls unaffected by vitiligo or any other autoimmune disorder. We found that two SNPs in the NALP1 extended promoter region, rs1008588 and rs2670660 were significantly associated with generalized vitiligo in our cohort of Arab vitiligo patients, and several other SNPs in the NALP1 region were at the margin of significant association. These results indicate that NALP1 is associated with susceptibility to generalized vitiligo in Arabs, as in Caucasians. Whether the casual variants are the same of not is yet to be identified by functional analysis. PMID- 20574745 TI - Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients. AB - The aim of this study was to evaluate pharmacokinetic parameters of fumaric acid esters (FAE) in psoriasis patients for the first time. For this prupose new HPLC assays were developed. Additionally, physicochemical parameters of FAE were determined, allowing a better interpretation of the in vivo data. In vivo, monomethylfumarate (MMF) and monoethylfumarate (MEF) were detected after t (lag) = 120 min. T (max) and c (max) of MMF were 210 min and 11.2 microM, respectively, 210 min and 5.2 microM for MEF. The half-life of MMF was 38.7 min, and 25.4 min of MEF. The AUC(0-infinity) of MMF was 172 min microg ml(-1) and 63.6 min microg ml(-1) of MEF. Data display median of three subjects. No plasma levels of dimethylfumarate (DMF) or fumaric acid (FA) were detected. The evaluation of physicochemical parameters of FAE showed that only DMF fulfils the criteria of Lipinski's rule of five. The pKa of MMF was determined as 3.63. The data of this study provide evidence that DMF is most likely absorbed out of the duodenum into the presystemic circulation and is not completely hydrolysed to MMF before uptake as assumed by others. PMID- 20574746 TI - Usher syndrome associated with Fuchs' heterochromic uveitis. AB - BACKGROUND: The purpose of this study is to report two new cases of Usher syndrome associated with Fuchs' heterochromic uveitis (FHU), to confirm our previous observation of the association between FHU and retinitis pigmentosa (RP), and to evaluate if FHU is particularly associated with Usher syndrome. METHODS: Retrospective medical record review of all new RP cases at Hadassah Medical Center between the years 2000 and 2007, review of our previously published data, and a meta-analysis of published relevant articles in peer reviewed journals. RESULTS: During the time frame of the study we diagnosed 58 new cases of RP, of whom one male and one female had the typical findings of FHU, and both had Usher syndrome type II. The difference in the occurrence of FHU between the 616 controls and the patients with RP was significant (p = 0.0073, Fisher's exact test). In our combined data, FHU occurred only in two types of RP; RP simplex with an incidence of 0.57%, and Usher syndrome with an incidence of 13.5%. This difference between the incidence of FHU in patients with Usher syndrome and other types of RP was significant (p < 0.0001, Fisher's exact test). Adding up these two cases with what is already published in the literature makes up a total of 17 RP patients with coexisting FHU. CONCLUSIONS: This study confirms the association between FHU and RP; and a particularly stronger association with Usher syndrome type II. Although infectious agents seem to play a role, the cause for this significant correlation is still unclear. PMID- 20574747 TI - Influence of combined treatment of low dose rapamycin and cyclosporin A on corneal allograft survival. AB - PURPOSE: To analyze the immune modulatory effect of low-dose systemic treatment with rapamycin (Rapa) alone or in combination with cyclosporin A (CsA) in a high responder corneal allograft model. METHODS: A total of 80 C57BL/6 mice received corneal grafts from BALB/c donors. Recipients were treated with either CsA 3 mg/kg/day or Rapa 0.5 mg/kg/day monotherapy or received combined treatment. Immunomodulatory treatment was started on the day of surgery, and continued for 14 days. The frequency of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Treg) in secondary lymphoid organs was measured by flow cytometry. Development of IFN gamma producing alloreactive T cells was estimated by Elispot. In addition, corneal samples were subjected to real-time RT-PCR analysis for cytokine transcription. RESULTS: Monotherapy with Rapa significantly delayed allograft rejection (13.4 +/- 1.34 days, p = 0.03). However, the combination of both, low dose Rapa and CsA prolonged corneal allograft survival at a significantly higher level (MST = 17.1 +/- 1.37 days, p = 0.0001) than in the control group (MST = 11.2 +/- 1.91 days). Rapa monotherapy increased the frequency of CD4(+)CD25(+)Foxp3(+)Treg in draining lymph nodes, whereas addition of CsA reduced Tregs. Monotherapy with Rapa as well as combined treatment prevented development of IFN-gamma producing alloreactive T cells in spleen. Combined treatment resulted in down-regulation of intragraft CD3, IL-2, IFN-gamma and IL 10 transcription (p = 0.028, p = 0.027, p = 0.028 and p = 0.027 respectively). CONCLUSIONS: Combined treatment with low-dose CsA and Rapa resulted in superior graft survival, and effectively modulated mRNA expression of inflammation and infiltration markers. PMID- 20574748 TI - Menorrhagia and ecchymoses in an adolescent girl treated with sertaline. PMID- 20574749 TI - Using the Edinburgh postnatal depression scale to screen for perinatal anxiety. AB - We replicated the factor structure of the anxiety subscale of the Edinburgh Postnatal Depression Scale (EPDS) in a large convenience sample of Western Australian women who participated in the beyondblue National Postnatal Depression Program. In addition, we determined an appropriate cut-off score for the anxiety subscale. Factor analyses conducted on the EPDS responses yielded depression and anxiety factors as identified in previous research. Two-factor solutions accounted for over 50% of the variance at two time frames: antenatally (N=4,706) and at postnatal follow-up (N=3,853). The anxiety and depression factors had similar factor structures antenatally and postnatally and were consistent with previous published findings. The concurrent validity of the anxiety subscale was demonstrated by its significant relationship to anxiety-related items on a psychosocial risk factors questionnaire. Anxiety dropped significantly from the antenatal to the postnatal time period. These findings confirm the anxiety subscale of the EPDS and point to its utility in screening for anxiety symptoms using a cut-off score >=4 which captured the top quartile of the antenatal sample. PMID- 20574750 TI - Absorbance changes accompanying the fast fluorescence induction in the purple bacterium Rhodobacter sphaeroides. AB - The authors present a study of the fluorescence and absorbance transients occurring in whole cells of purple nonsulfur bacterium Rhodobacter sphaeroides on the millisecond timescale under pulsed actinic illumination. The fluorescence induction curve is interpreted in terms of combination of effects of redox changes in the reaction center and the membrane potential. The results of this study support the view that the membrane potential act predominantly to increase the fluorescence yield. Advantages of the pulsed actinic illumination for study of the operation of the electron transport chain in vivo are discussed. PMID- 20574751 TI - [Bilateral injuries of the internal mammary artery following blunt thoracic trauma]. AB - Injuries of the internal mammary artery after blunt thoracic trauma are rare but potentially fatal. A specific characteristic of these injuries is that they can become symptomatic even after a delay of several weeks. This article reports on the diagnosis and treatment of a 41-year-old motorcycle rider who suffered bilateral injuries of the internal mammary artery after a motorcycle accident without any additional bony lesions. PMID- 20574752 TI - [Evaluation and management of enuresis. An update]. AB - Enuresis is defined as nocturnal bed wetting for at least 2 nights per month in children older than 5 years. At this age the prevalence of enuresis is about 15 20%. More than 50% of these children show day time symptoms, such as frequency, urgency and incontinence (non-monosymptomatic enuresis). The other children are asymptomatic during day time and wet the bed during the night time (monosymptomatic enuresis). The main pathogenetic factors are nycturia, detrusor overactivity and reduced arousability. Psychological and psychiatric aspects, genetics and obstipation play an additional role in the etiology. Basic diagnostic investigations are mandatory before treatment. Clinical history, physical examination, sonography of the urinary tract, urinalysis and bladder diary are prerequisites before any therapeutic steps are taken. The cornerstones of primary enuresis therapy are general lifestyle advice, pharmacotherapy and alarm devices. Therapy-resistant children deserve further evaluation and a multidisciplinary therapy approach. After careful evaluation specific therapy is efficient in approximately 80% of patients. PMID- 20574753 TI - Subcutaneous immunoglobulin therapy for the treatment of multifocal motor neuropathy: a case report. AB - Multifocal motor neuropathy (MMN) is a rare immune-mediated disease characterized by slowly progressive, asymmetric, predominantly distal weakness of one or more limbs without sensory loss. The first line of treatment is high-dose intravenous immunoglobulins (IVIg). Subcutaneous immunoglobulins (SCIg)already approved for the treatment of primary immune deficiency have recently been proposed also for the treatment of disimmune peripheral neuropathies such as MMN, and a few trials were performed to see if patients receiving immunomodulatory doses of IVIg could be treated equally well with SCIg. We describe a patient affected by MMN who was included in a protocol of treatment with SCIg for a period of 6 months. He successfully responded to treatment with a stabilization of strength. The patient is still treated with SCIg even after the end of the protocol. This is the first description of an Italian case of a patient affected by MMN successfully treated with SCIg. PMID- 20574754 TI - Fertility after cesarean delivery among Somali-born women resident in the USA. AB - We evaluated the reproductive impact of cesarean versus vaginal delivery in Somali immigrants. Data were extracted for 106 Somali women delivering vaginally (64%) or by cesarean section (36%) between 1994 and 2006. Index delivery (vaginal versus cesarean) was compared to the cumulative incidence rate of subsequent deliveries. The incidence rate of a delivery after a vaginal delivery was 3.3% (CI:0-7.8%), 55.4% (CI:40.1-66.8%) and 74.4% (CI:59.0-84.0%) at 1, 2 and 3 years. Cesarean delivery lead to a second delivery incidence rate of 2.9%(95%CI:0-8.2%), 25.9%(95%CI:9.8-39.2%) and 58.1% (95%CI:27.0-72.2%) at 1, 2 and 3 years. Somali women delivering vaginally were 1.56 times (95% CI:0.94-2.57; P = 0.084) more likely to have a subsequent delivery. The likelihood of Somali women having a second child after cesarean section is lower at 2 and 3 year follow-up. PMID- 20574755 TI - Extracellular accumulation of recombinant protein by Escherichia coli in a defined medium. AB - Extracellular accumulation of recombinant proteins in the culture medium of Escherichia coli is desirable but difficult to obtain. The inner or cytoplasmic membrane and the outer membrane of E. coli are two barriers for releasing recombinant proteins expressed in the cytoplasm into the culture medium. Even if recombinant proteins have been exported into the periplasm, a space between the outer membrane and the inner membrane, the outer membrane remains the last barrier for their extracellular release. However, when E. coli was cultured in a particular defined medium, recombinant proteins exported into the periplasm could diffuse into the culture medium automatically. If a nonionic detergent, Triton X 100, was added in the medium, recombinant proteins expressed in the cytoplasm could also be released into the culture medium. It was then that extracellular accumulation of recombinant proteins could be obtained by exporting them into the periplasm or releasing them from the cytoplasm with Triton X-100 addition. The tactics described herein provided simple and valuable methods for achieving extracellular production of recombinant proteins in E. coli. PMID- 20574756 TI - Combined oral anticoagulant and antiplatelet treatment: need for an evidence based approach. PMID- 20574757 TI - Oughtonomy in healthcare. A deconstructive reading of Kantian autonomy. AB - For years now, autonomy has been discussed as one of the central values in health care. Understood as self-realization, it is opposed to paternalism which is conceived as an intolerable occurrence of heteronomy. Although different concepts have been developed to nuance this opposition, when it comes to health care discourse, heteronomy is still the enemy of autonomy. In our article, we defend the thesis that autonomy is only achievable as heteronomy. We are not arguing for an expansion of the meaning of autonomy, but are attempting to conduct an analysis which lays bare the 'disrupting' attendance of heteronomy within the principle of autonomy. Autonomy does not begin where heteronomy ends, but can only begin if heteronomy is already involved. To emphasize this, we prefer to elaborate a new concept: 'oughtonomy'. This concept is inspired by Jacques Derrida's distinction between 'difference' and 'differance'. We will develop the concept of oughtonomy from a deconstructive reading of Kant's idea of autonomy, inspired by philosophers such as Jacob Rogozinski, Jean-Luc Nancy and others. In addition to a first exploration of this concept, this article also discusses the possible consequences of oughtonomy for current debates concerning health care. Our quest for a new understanding of autonomy is motivated by the concern that, although the accent on autonomy as self-realization and independence has many advantages, we should also bear in mind the countless disadvantages. PMID- 20574758 TI - The efficacy of serial serum amyloid A measurements for diagnosis and follow-up of necrotizing enterocolitis in premature infants. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of serial serum amyloid A (SAA) measurements in diagnosis and follow-up of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A total of 144 infants were enrolled in this observational study. The infants were classified into three groups: group 1 (infants with NEC and sepsis), group 2 (infants with sepsis), and group 3 (no sepsis and NEC, control group). Data including serial whole blood count (WBC), SAA measurements that were obtained at the initial work-up of NEC and/or sepsis episode (0 day), at 24, 48 h, 7, and 10 day were evaluated. In addition, initial and serial follow-up abdominal radiographies were obtained. RESULTS: A total of 50 infants were diagnosed NEC. Mean SAA values (43.2 +/- 47.5 mg/dl) of infants in group 1 at 0 h were significantly higher than those in group 2 and group 3. The percentage of infants with abnormal SAA levels was significantly higher in group 1 compared with that in group 2 at 24 h. In addition, the percentage of infants with abnormal SAA levels was slightly but not statistically higher in stage 2 and stage 3 NEC group compared with that stage 1 NEC at 0, 24, 48 h. SAA levels started to decline at 48 h of onset through day 10. The cut-off value for SAA for differentiating NEC from sepsis was 23.2 mg/dl. CONCLUSION: SAA may be recognized as an accurate laboratory marker in addition to clinical and radiographic findings for NEC diagnosis. It can also be used for determining the severity of NEC and response to therapy in infants with NEC. PMID- 20574759 TI - The autocrine motility factor receptor is overexpressed on the surface of B cells in Binet C chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a clinical spectrum reaching from discrete lymphocytosis to extensive enlargement of lymph nodes, spleen and liver, and bone marrow failure. The aim of this study was to identify genes that differentiate between patients with disease stage A vs. C according to Binet in order to better understand the disease. To achieve this, we performed DNA microarray analysis on B cells from CLL patients with stage A and C according to Binet and matched controls. Between CLL patients and controls, there were 1,528 differentially expressed genes and 360 genes were differentially expressed between Binet A and C patients. Due to the sheer number of regulated genes, we focused on the autocrine motility factor receptor (AMFR). AMFR has not previously been investigated in hematological disorders, but high expression of AMFR correlates with a more advanced stage and invasive potential in several human tumors. AMFR mRNA expression was higher in Binet A compared with Binet C patients (P=0.0053) and healthy controls (P=0.0051). Total AMFR protein was higher in Binet A patients compared to Binet C as analyzed by intracellular flow cytometry. However, AMFR exist both in the ER involved in protein degradation and on the cell surface involved in metastasis and cell motility. Cell surface AMFR was increased in Binet C compared with Binet A+B (P=0.016). In conclusion, the mRNA levels reflect the total amount of AMFR, whereas cell surface expression is associated with progression in CLL. PMID- 20574760 TI - [Cleft in carbon dioxide absorber. Intraoperative problems with ventilation due to a leak in the breathing circuit]. AB - In the case presented problems with mechanical and manual ventilation of a patient occurred during the operation. Prior to this endotracheal intubation had been performed without difficulty and the respirator had passed all system checks. A leakage in the recently changed carbon dioxide absorber could be detected which had been accidentally dropped and damaged internally. PMID- 20574762 TI - [Intrathecal opioid medication for perioperative analgesia in severely handicapped children undergoing spinal operations]. AB - PURPOSE OF THE STUDY: Intrathecal opioids have been shown to be safe and effective for postoperative analgesia in healthy children for spinal surgery. The aim of this study was to evaluate the applicability of intrathecal opioids in severely handicapped children scheduled for spinal surgery. METHODS: With hospital ethical committee approval, patients with physical states III and IV of the ASA classification requiring spinal surgery were retrospectively studied. In addition to inhalational anesthesia with sevoflurane or intravenous anesthesia using propofol, morphine 20 microg/kgBW and sufentanil 1.5 microg/kgBW were administered intrathecally before surgery. After surgery an infusion of nalbuphine was started. Need for additional intraoperative and postoperative analgesics, time of extubation, postoperative pain scores and p(a)CO2 values as well as adverse effects were recorded. RESULTS: A total of 28 patients aged from 2.8 to 18.5 years (median 11.6 years) were studied. Immediate tracheal extubation in the operating room was possible in 17 patients and for 11 patients delayed extubation was elected. All patients were extubated within 24 h except for 1 patient who received massive postoperative transfusions. In 26 out of 28 patients (93%) the combination of intrathecal opioids with postoperative nalbuphine provided adequate analgesia. Observed side effects were post-operative nausea and vomiting (PONV), pruritus and moderate hypoventilation. In two patients a change to intravenous morphine therapy was necessary. CONCLUSION: The use of intrathecal opioids for perioperative pain control from spinal fusion in severely handicapped children is feasible. Intrathecal opioids provide adequate postoperative analgesia and allow early extubation without persisting relevant respiratory compromise in most of these patients. PMID- 20574763 TI - Vesicular glutamate transporter 2 is associated with the cochlear nucleus commissural pathway. AB - The cochlear nucleus (CN) is the first auditory structure to receive binaural information via CN-commissural connections. In spite of an abundance of evidence that CN-commissural neurons are glycinergic and thus inhibitory, physiological, and anatomical evidence suggests that a small group of CN-commissural neurons are excitatory. In this study, we examined the excitatory portion of the CN commissural pathway by combining anterograde tract tracing with immunohistochemistry of vesicular glutamate transporters (VGLUTs) and retrograde tract tracing with immunohistochemistry of glycine and GABA. VGLUTs accumulate glutamate in synaptic vesicles and are prime markers for glutamatergic neurons. The terminal endings of CN-commissural projections were typically en passant or small terminal boutons, but large, irregular swellings were also observed, confined to the granule cell domain (GCD). Both small and large terminal endings in the GCD colabeled with VGLUT2, but not VGLUT1. In addition, some CN commissural cells themselves received VGLUT2-positive puncta on their somata. After large injections into the CN, 37% of the total number of retrogradely labeled commissural neurons was immunonegative to glycine or GABA. Retrograde labeling after a restricted GCD injection revealed a majority of putative excitatory CN-commissural neurons as multipolar, in the marginal regions of the ventral CN, medially as well as in the small cell cap region and deep dorsal CN. These results provide direct anatomical evidence that an excitatory commissural projection is present, and VGLUT2 is associated with this pathway both as its source and as a recipient. PMID- 20574764 TI - Decrease in propagation of interictal epileptiform activity after introduction of levetiracetam visualized with electric source imaging. AB - Different neuroimaging techniques (fMRI, spectroscopy, PET) are being used to evaluate candidate drugs in pharmacological development. In patients with epilepsy fast propagation of the epileptiform activity between different brain areas occurs. Electric Source Imaging (ESI), in contrast to the aforementioned techniques, has a millisecond time resolution, allowing visualization of this fast propagation. The purpose of the current project was to use ESI to investigate whether introduction of an antiepileptic drug (levetiracetam, LEV) would change the propagation patterns of the interictal epileptiform activity. Thirty patients with epilepsy were subject to an EEG recording before (pre-LEV) and after (in-LEV) introduction of LEV. Interictal spikes with similar topographic distribution were averaged within each subject, and a distributed source model was used to localize the EEG sources of the epileptiform activity. The temporal development of the activity within 20 regions of interest (ROIs) was determined, and source propagation between different regions was compared between the pre-LEV and in-LEV recordings. Patients with epileptic seizures showed propagation in 22/24 identified spike types in the pre-LEV recordings. In the in LEV recordings only 7/15 spike types showed propagation, and six of these seven propagating spikes were recorded in patients with poor effect of treatment. Also in patients without seizures LEV tended to suppress propagation. We conclude that the observed suppression of source propagation can be considered as an indicator of effective antiepileptic treatment. ESI might thus become a useful tool in the early clinical evaluation of new candidate drugs in pharmacological development. PMID- 20574765 TI - Ageing and health care expenditure in EU-15. AB - The purpose of this paper is to investigate the relationship between ageing and the evolution of health care expenditure per capita in the EU-15 countries. A secondary purpose is to produce estimates that can be used in projections of future health care costs. Explanatory variables include economic, social, demographic and institutional variables as well as variables related to capacity and production technology in the health care sector. The study applies a co integrated panel data regression approach to derive short-run relationships and furthermore reports long-run relationships between health care expenditure and the explanatory variables. Our findings suggest that there is a positive short run effect of ageing on health care expenditure, but that the long-run effect of ageing is approximately zero. We find life expectancy to be a more important driver. Although the short-run effect of life expectancy on expenditure is approximately zero, we find that the long-run effect is positive, so that increasing life expectancy leads to a more than proportional, i.e. exponential, increase in health care expenditure. PMID- 20574766 TI - Optoelectronic stimulation of the brain using carbon nanotubes. AB - This paper presents the simulation results of a novel technique to stimulate the brain using a carbon nanotubes (CNT) based optically activated stimulator. This technique could be a promising alternative solution to overcome the limitations occurring in the conventional electrical stimulation of the brain and the newly developed opto-genetic stimulation. In this technique, the CNT stimulator, which generated an electrical current when exposed to light, was implanted in the brain. This current stimulated the nearby neurons to generate an action potential. The simulation results illustrated that a single-wall carbon nanotube of 50 nm2 size could stimulate a 40 MUm2 area of the brain, whereas a multiwall carbon nanotube could cover a 12 MUm2 area of the brain. Additionally, simulations were also performed to determine the optimal shape and appropriate coating material for commercial optical stimulators to maximize the stimulation efficacy in the brain. PMID- 20574767 TI - Multi-scale regularization approaches of non-parametric deformable registrations. AB - Most deformation algorithms use a single-value smoother during optimization. We investigate multi-scale regularizations (smoothers) during the multi-resolution iteration of two non-parametric deformable registrations (demons and diffeomorphic algorithms) and compare them to a conventional single-value smoother. Our results show that as smoothers increase, their convergence rate decreases; however, smaller smoothers also have a large negative value of the Jacobian determinant suggesting that the one-to-one mapping has been lost; i.e., image morphology is not preserved. A better one-to-one mapping of the multi-scale scheme has also been established by the residual vector field measures. In the demons method, the multi-scale smoother calculates faster than the large single value smoother (Gaussian kernel width larger than 0.5) and is equivalent to the smallest single-value smoother (Gaussian kernel width equals to 0.5 in this study). For the diffeomorphic algorithm, since our multi-scale smoothers were implemented at the deformation field and the update field, calculation times are longer. For the deformed images in this study, the similarity measured by mean square error, normal correlation, and visual comparisons show that the multi scale implementation has better results than large single-value smoothers, and better or equivalent for smallest single-value smoother. Between the two deformable registrations, diffeormophic method constructs better coherence space of the deformation field while the deformation is large between images. PMID- 20574768 TI - The role of noninvasive imaging in promoting cardiovascular health. AB - Cardiovascular disease (CVD) is the leading cause of death worldwide, and its prevalence is likely to increase in the near future. The morbidity and mortality associated with CVD causes an enormous economic burden, which has become a major problem for many societies across the globe. The current prevention strategies are aimed at identifying and reducing established risk factors for atherosclerosis including hypertension, hypercholesterolemia, diabetes, obesity, smoking, and sedentary lifestyle. However, some of our prevention goals, such as reducing LDL cholesterol, change dramatically once a subject has been diagnosed with coronary atherosclerosis. At the present time, atherosclerosis is frequently diagnosed relatively late in the course of the disease, when a patient develops symptoms or presents with acute events such as an acute coronary syndrome or a stroke. Several studies have demonstrated that novel noninvasive imaging techniques have the potential to identify subclinical atherosclerosis and high risk plaques. Early detection of subclinical atherosclerosis may enable clinicians to improve the control of cardiovascular risk factors in affected patients earlier, thereby helping to prevent some of the manifestations of CVD. PMID- 20574769 TI - Central and peripheral anti-inflammatory effects of maprotiline on carrageenan induced paw edema in rats. AB - OBJECTIVE: To explore the site of action of maprotiline, as an atypical antidepressant, on carrageenan-induced paw edema. SUBJECTS: Male Wistar rats were used. METHODS: Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg(-1)) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg( 1)), prazosin (4 mg kg(-1)), yohimbine (10 mg kg(-1)), naloxone (4 mg kg(-1)) and mifepristone (5 mg kg(-1)). RESULTS: Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline. CONCLUSION: These results demonstrate that maprotiline has a potent anti inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug. PMID- 20574770 TI - Generation of polyclonal antibodies against recombinant human glucocerebrosidase produced in Escherichia coli. AB - Deficiency of the lysosomal glucocerebrosidase (GCR) enzyme results in Gaucher's disease, the most common inherited storage disorder. Treatment consists of enzyme replacement therapy by the administration of recombinant GCR produced in Chinese hamster ovary cells. The production of anti-GCR antibodies has already been described with placenta-derived human GCR that requires successive chromatographic procedures. Here, we report a practical and efficient method to obtain anti-GCR polyclonal antibodies against recombinant GCR produced in Escherichia coli and further purified by a single step through nickel affinity chromatography. The purified GCR was used to immunize BALB/c mice and the induction of anti-GCR antibodies was evaluated by enzyme-linked immunosorbent assay. The specificity of the antiserum was also evaluated by western blot analysis against recombinant GCR produced by COS-7 cells or against endogenous GCR of human cell lines. GCR was strongly recognized by the produced antibodies, either as cell-associated or as secreted forms. The detected molecular masses of 59-66 kDa are in accordance to the expected size for glycosylated GCR. The GCR produced in E. coli would facilitate the production of polyclonal (shown here) and monoclonal antibodies and their use in the characterization of new biosimilar recombinant GCRs coming in the near future. PMID- 20574771 TI - Enhanced extracellular production of heterologous proteins in Bacillus subtilis by deleting the C-terminal region of the SecA secretory machinery. AB - In this study, we examined the effects of modifying the C-terminal region of the SecA protein on the production of heterologous proteins in Bacillus subtilis. SecA was selected as a candidate among the components of the Sec system due to its ability to interact directly with both the precursors and membrane translocases. A phylogenetic comparison demonstrated that the C-terminal region is not well conserved among eubacterial SecA proteins. The deletion of the 61 amino acids at the C-terminal region led to an 83% increase in extracellular alkaliphilic Bacillus sp. thermostable alkaline cellulase (Egl-237) activity. Moreover, the productivity of human interferon alpha (hIFN-alpha2b) was increased by 2.2-fold compared to the wild-type SecA, by deletion of these 61 amino acids. We indicated that the deletion of the C-terminal domain (CTD) of SecA enhanced the secretion of two different heterologous protein, Egl-237 and hIFN-alpha2b. This study provides a useful method to enhance the extracellular production of heterologous proteins in B. subtilis. PMID- 20574772 TI - The short peritoneal equilibration test in pediatric peritoneal dialysis. AB - The peritoneal equilibration test (PET) is the gold standard method for defining peritoneal membrane permeability and for prescribing peritoneal dialysis (PD) therapy on an individual basis. However, it is laborious, consumes nursing time, and requires many hours to be performed. Therefore, several authors have attempted to validate a short PET protocol, with controversial results. To evaluate the concordance between the 2-h (short) and 4-h (classical) peritoneal equilibrium test, a prospective observational protocol was applied in three PD centers (Mexico, Chile, and Uruguay) between July 1, 2008 and July 31 2009. PET protocol: the night prior to the test, each patient received five exchanges, 1 h each, at the same glucose concentration as previously used. Afterwards, a 2.5% glucose dialysis solution was used for a dwell time of 4 h. Exchange fill volume was 1,100 ml/m2 body surface area. The next morning, the 4-h dwell was drained, and Dianeal 2.5% was infused. Three dialysate samples at 0, 2, and 4 h were obtained. A single blood sample was obtained at 120 min. Creatinine D/P and glucose D/D0 ratios were calculated at hours 0, 2, and 4. Patients were categorized as low, low average, high average, or high transporters according creat D/P and gluc D/D0 results. Pearson and Kappa test were used for numerical and categorical correlations, respectively, and p<0.05 was considered significant. Eighty-seven PET studies were evaluated in 74 patients, 33 males, age 11.1+/-5.05 years old. A positive linear correlation of 92% between 2 and 4-h creat D/P and 80% between 2 and 4-h gluc D/D0 (p<0.001) was founded. The Kappa test showed a significant concordance between creat D/P and gluc D/D0 categories at 2 and 4 h (p<0.001). When analyzing cut-off-value categories, creat D/P was founded to be lower and gluc D/D0 higher than other experiences. This multicentric prospective study strongly suggests that PET obtained at 2 h and 4 h, based on either creatinine or glucose transport, provides identical characterization of peritoneal membrane transport capacity in PD children. PMID- 20574773 TI - Radiosurgery of liver tumors: value of robotic radiosurgical device to treat liver tumors. AB - BACKGROUND: The treatment of isolated liver metastases has become a rapidly developing field with many new, technically advanced methods. Here we present the therapeutic efficacy of a robotic radiosurgery for local control of liver metastases from solid tumors. METHODS: Patients with tumorous lesions to the liver, not qualifying for surgery, were treated with single-session radiosurgery (24 Gy) that used robotic image-guided real-time tumor tracking. All detectable lesions had to be irradiated. In a prospective analysis, follow-up was performed by magnetic resonance imaging scanning 2 months after the treatment, and subsequently at 3-month intervals to evaluate local control. For inclusion into the radiosurgery treatment protocol, tumor volumes had to be <90 ml. RESULTS: Thirty-six patients (median age, 65 years) with a total of 54 target lesions were evaluated. Single lesions were treated in 23 patients and multiple targets in 13 patients. Metastases originated from colon cancer (n = 19), ovarian cancer (n = 3), pancreatic cancer (n = 2), breast cancer (n = 2), and others (n = 6). Four lesions were of primary liver origin (hepatocellular carcinoma and cholangiocellular carcinoma). Median tumor volume was 18 ml (range, 2.2-90 ml). The median follow-up was 21.3 months. The disease of 25 patients (69.4%) showed complete or partial local response, 6 patients (16.7%) had stable lesions, and 5 patients (14%) experienced local recurrence. Grade 2-4 adverse events due to radiation treatment were not observed. CONCLUSIONS: Robotic radiosurgery with image-guided real-time tumor tracking of liver neoplasm is a new and promising approach for patients with disease that is not eligible for surgical resection and might enhance the possibilities of multidisciplinary oncological treatment concepts. PMID- 20574774 TI - Morbidity of sentinel node biopsy in breast cancer: the relationship between the number of excised lymph nodes and lymphedema. AB - BACKGROUND: Despite the reduced morbidity associated with sentinel lymph node biopsy (SLNB), lymphedema remains a clinically relevant complication. We hypothesized that a higher number of lymph nodes (LNs) removed during SLNB is associated with a higher risk of lymphedema. METHODS: Six hundred patients with clinically node-negative breast cancer who underwent SLNB were prospectively studied. Circumferential bilateral upper extremity measurements were performed preoperatively and at 3-8 years after surgery. Association of lymphedema with total number of LNs excised and other clinicopathologic variables was analyzed by the Spearman rank correlation coefficient, Fisher's exact test, Wilcoxon rank sum test, and logistic regression. RESULTS: At a median follow-up of 5 years, 5% of patients had developed lymphedema. Factors associated with lymphedema included weight and body mass index. There was no association between the number of LNs removed and the change in upper extremity measurements or in the incidence of lymphedema. Among patients with lymphedema (n = 31) compared to those without, the mean (3.9 vs. 4.2), median (4 vs. 3), and range (1-9 vs. 1-17) of number of LNs removed were similar (P = 0.93). Among the 33 women with >= 10 LNs removed, none developed lymphedema. CONCLUSIONS: In this population of 600 women who underwent SLNB, there is no correlation between number of LNs removed and change in upper extremity circumference or incidence of lymphedema. These data suggest that other factors, such as the global disruption of the lymphatic channels during axillary lymph node dissection, play a larger role in development of lymphedema than does the number of LNs removed. PMID- 20574775 TI - Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort. AB - PURPOSE: Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population. METHODS: Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity matched controls. RESULTS: Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P < 0.001; OR, 2.62; 95%CI, 1.71-4.03) and PR + RR (P < 0.001; OR, 2.59; 95%CI, 1.72-3.91) genotypes, and in R allele (P < 0.001; OR, 2.05; 95%CI, 1.47-2.85). Furthermore, significant association between MMP-9 Q279R, P574R polymorphism and smoking was observed in BC risk. Haplotype analysis too revealed significant association with 5A-A-G of MMP-3 haplotype (P = 0.022; OR, 1.99; 95%CI, 1.11-3.60) and with R-R (P = 0.001; OR, 2.00; 95%CI, 1.35-2.97) and Q-R (P < 0.001; OR, 2.97; 95%CI, 1.65-5.37) of MMP-9 haplotype. Genotype 5A/6A of MMP-3 1171 showed borderline risk and high recurrence-free survival in Bacillus Calmette-Guerin (BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025). CONCLUSION: Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC. PMID- 20574776 TI - High HIV prevalence and diagnosis rates in New York City black men. AB - We sought to identify population and subpopulation disparities in rates of HIV diagnosis and prevalence among black males 13 years and older in New York City. We used population-based data from the New York City HIV/AIDS surveillance registry and US Census 2000 to calculate HIV prevalence in 2006 and HIV diagnosis rates in 2007. Black males were the largest demographic group of new HIV diagnoses (n = 1,161, 33%) and persons living with HIV/AIDS in New York City (n = 24,294, 29%) and had the highest diagnosis rates (1.7 per 1,000 population) and prevalence (3.7%). Prevalence and diagnosis rates among black males were higher in higher-poverty neighborhoods than in lower-poverty neighborhoods (p < 0.01). However, very high prevalence (19.3%) was found among black males in three adjacent Manhattan neighborhoods with relatively low poverty rates, and where overall diagnosis rates among black males (7.4 per 1,000) and proportions attributable to men who have sex with men (60.0%) were high. HIV-related disparities exist not only between black males and other groups but also within black males. Success addressing the citywide HIV epidemic will be linked to success in the various portions of this highly affected, heterogeneous population. PMID- 20574777 TI - Social determinants of physical inactivity in the Northern Manhattan Study (NOMAS). AB - Physical inactivity is an important and modifiable cardiovascular disease risk factor. Little is known about the social determinants of physical inactivity in older, urban-dwelling populations. We collected socio-demographic and medical risk factor information and physical activity questionnaires in the Northern Manhattan Study. Logistic regression models were constructed to examine whether measures of social isolation, race-ethnicity, and sex were associated with physical inactivity. Physical inactivity was present in 40.5% of the cohort. In multivariable models adjusted for medical comorbidities, Hispanic race-ethnicity (compared to non-Hispanic white) was associated with higher odds of physical inactivity (OR 2.18, 95% CI 1.78, 2.67), while women were more likely to be inactive than men (OR 1.33, 95% CI 1.15, 1.54). Having Medicaid/being uninsured (OR 1.20, 95% CI 1.02, 1.42), and having fewer than 3 friends (1.41, 95% CI 1.15, 1.72) were also associated with physical inactivity. Physical inactivity is common, particularly in Hispanics, women, and those who are socially isolated. Public health interventions aimed at increasing physical activity in these more sedentary groups are required. PMID- 20574778 TI - Electronegative low-density lipoprotein is associated with dense low-density lipoprotein in subjects with different levels of cardiovascular risk. AB - Dyslipidemias and physicochemical changes in low-density lipoprotein (LDL) are very important factors for the development of coronary artery disease (CAD). However, pathophysiological properties of electronegative low-density lipoprotein [LDL(-)] remain a controversial issue. Our objective was to investigate LDL(-) content in LDL and its subfractions (phenotypes A and B) of subjects with different cardiovascular risk. Seventy-three subjects were randomized into three groups: normolipidemic (N; n = 30) and hypercholesterolemic (HC; n = 33) subjects and patients with CAD (n = 10). After fasting, blood samples were collected and total, dense and light LDL were isolated. LDL(-) content in total LDL and its subfractions was determined by ELISA. LDL(-) content in total LDL was lower in the N group as compared to the HC (P < 0.001) and CAD (P = 0.006) groups. In the total sample and in those of the N, HC, and CAD groups, LDL(-) content in dense LDL was higher than in light LDL (P = 0.001, 0.001, 0.001, and 0.033, respectively) The impact of LDL(-) on cardiovascular risk was reinforced when LDL(-) content in LDL showed itself to have a positive association with total cholesterol (beta = 0.003; P < 0.001), LDL-C (beta = 0.003; p < 0.001), and non HDL-C (beta = 0.003; P < 0.001) and a negative association with HDL-C (beta = 0.32; P = 0.04). Therefore, LDL(-) is an important biomarker that showed association with the lipid profile and the level of cardiovascular risk. PMID- 20574779 TI - Serum polyunsaturated fatty acids are not associated with the risk of severe depression in middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study. AB - PURPOSE: The aim of this study is to investigate whether serum n - 3 polyunsaturated fatty acids (PUFAs) or n - 6 to n - 3 ratio is associated with risk of severe depression in middle-aged Finnish men. METHODS: The association between the serum concentrations of fatty acids and depression was investigated in 2077 men aged 42-60 years at baseline in a prospective follow-up setting. The population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study cohort was recruited between 1984 and 1989 and followed until the end of 2007. The baseline levels of serum total n - 3 PUFAs, n - 6 PUFAs and individual fatty acids were determined. Data on hospital treatments due to major depressive disorder were derived from the national hospital discharge register. RESULTS: During the average follow-up time of 18 years, 46 men received a discharge diagnosis of depression. When the Cox proportional hazards model was adjusted for age, examination year, baseline socioeconomic status, alcohol consumption, smoking, maximal oxygen uptake and body mass index, there was no association between serum total n - 3 PUFAs and the risk of depression [relative risk (RR) in the highest compared to the lowest tertile 0.71, 95% confidence interval (CI): 0.38; 1.43]. Serum concentrations of n - 6 PUFAs, n6/n3 PUFA ratio, or individual fatty acids were not associated with the risk of severe depression, either. CONCLUSIONS: We did not find evidence that serum n - 3 PUFA concentration or n - 6/n - 3 ratio would be associated with risk of severe depression in middle-aged Finnish men. PMID- 20574780 TI - Persistent aryl hydrocarbon receptor inducers increase with altitude, and estrogen-like disrupters are low in soils of the Alps. AB - BACKGROUND: Soil samples from remote Alpine areas were analyzed for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans and polychlorinated biphenyls by high-resolution gas chromatography/high-resolution gas spectrometry. Additionally, the EROD micro-assay and a genetically modified yeast estrogen bioassay were carried out to determine persistent aryl hydrocarbon receptors (AhR) and estrogen receptors (ER) agonists, respectively. Regarding the AhR agonists, the toxicity equivalents of analytical and EROD determined values were compared, targeting both altitude of samples and their soil organic content. The ratio between bioassay derived equivalents and analytical determinations suggested no significant contribution of unknown AhR inducers in these sampling sites and some antagonism in soils with relatively high PCB loading. More CYP1A1 expression was induced at the highest sites or about 1400-1500 m a.s.l. along the altitude profiles. Surprisingly, no clear tendencies with the soil organic content were found for dioxin-like compounds. Mean values obtained in the present study were for ER agonists, 2: 0.37+/-0.12ng 17beta-estradiol EQ g-1 dry soil [corrected] and 6.1 +/- 4.2 pg TCDD-EQ g-1 dry soil for AhR agonists. CONCLUSION: Low bioassay responses with a higher relative amount of ER disrupters than AhR inducers were detected,indicating the higher abundance of estrogen-like than persistent dioxin-like compounds in these forested areas [corrected]. PMID- 20574781 TI - Effects of acetaminophen in Brassica juncea L. Czern.: investigation of uptake, translocation, detoxification, and the induced defense pathways. AB - PURPOSE: Besides classical organic pollutants and pesticides, pharmaceuticals and their residues have nowadays become recognized as relevant environmental contaminants. The risks of these chemicals for aquatic ecosystems are well known, but information about the pharmaca-plant interactions and metabolic pathways is scarce. Therefore, we investigate the process of uptake of acetaminophen (N Acetyl-4-aminophenol) by Brassica juncea, drug-induced defense responses and detoxification mechanisms in different plant parts. MATERIAL AND METHODS: Hydroponically grown Indian mustard (Brassica juncea L. Czern.) plants were treated with acetaminophen and root and leaf samples were collected after 24, 72, and 168 h of treatment. The uptake of acetaminophen and the formation of its metabolites were analyzed using LC-MS/MS technique and enzyme activities including glutathione S-transferases (GSTs) as well as several plant defense enzymes like catalase, ascorbat peroxidase, peroxidase, and glutathione reductase were assayed spectrophotometrically. RESULTS: We determined the uptake and the translocation of acetaminophen, and we tried to identify the steps of the detoxification process by assaying typical enzymes, supposing the involvement of the same- or similar enzymes and reactions as in the mammalian detoxification process. After 24-h exposure, effective uptake and translocation were observed to the upper part of plants followed by two independent conjugative detoxification pathways. Changes in antioxidant defense enzyme activities connected to the defense pathway towards reactive oxygen species indicate an additional oxidative stress response in the plants. CONCLUSIONS: The major metabolic pathways in mammals are conjugation with activated sulfate and glucuronic acid, while a small amount of acetaminophen forms a chemically reactive and highly toxic, hydroxylated metabolite. We identified a glutathionyl and a glycoside conjugate, which refer to the similarities to mammalian detoxification. Increased GST activities in leaf tissues were observed correlated with the appearance of the acetaminophen-glutathione conjugate which shows the involvement of this enzyme group in the metabolism of acetaminophen in plants to organic pollutants and xenobiotics. High acetaminophen concentrations lead to oxidative stress and irreversible damages in the plants, which necessitates further investigations using lower drug concentrations for the deeper understanding of the induced detoxification-and defense processes. PMID- 20574782 TI - Temporal resolution of protein-protein interactions in the live-cell plasma membrane. AB - We have recently devised a method to quantify interactions between a membrane protein ("bait") and a fluorophore-labeled protein ("prey") directly in the live cell plasma membrane (Schwarzenbacher et al. Nature Methods 5:1053-1060 2008). The idea is to seed cells on surfaces containing micro-patterned antibodies against the exoplasmic domain of the bait, and monitor the co-patterning of the fluorescent prey via fluorescence microscopy. Here, we characterized the time course of bait and prey micropattern formation upon seeding the cells onto the micro-biochip. Patterns were formed immediately after contact of the cells with the surface. Cells were able to migrate over the chip surface without affecting the micropattern contrast, which remained constant over hours. On single cells, bait contrast may be subject to fluctuations, indicating that the bait can be released from and recaptured on the micropatterns. We conclude that interaction studies can be performed at any time-point ranging from 5 min to several hours post seeding. Monitoring interactions with time opens up the possibility for new assays, which are briefly sketched in the discussion section. PMID- 20574783 TI - Investigation of the interaction of Mercurochrome constituents with proteins using liquid chromatography/mass spectrometry. AB - The interaction of Mercurochrome, a medical preparation based on the mercury organic compound merbromin, with free thiols in low molecular weight peptides and in proteins has been investigated by means of liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS). Beta-lactoglobulin A (beta-LGA) from bovine milk (18.4 kDa) has been used as the model protein. It was found that, in contrast to assumptions in literature, the commercial product itself is a heterogeneous mixture of moderate chemical stability, which may contain precipitated Hg salts depending on storage time and conditions. Further variability results from different degrees of bromination of the fluorescein backbone of the compound. The formation of mercury compound-protein adducts was detected. The peptide sequence T13 containing a free thiol residue was identified as the binding site for mercury species after tryptic digestion of beta lactoglobulin A. While fresh Mercurochrome tends to the formation of a Hg(II) beta-LGA adducts due to excess Hg(2+) in solution, investigations after precipitation of Hg salts yield Hg(merbromin)(beta-LGA) as the major product. PMID- 20574784 TI - Purine bases oxidation and repair following permethrin insecticide treatment in rat heart cells. AB - Pollutants including insecticides have been recently reported to be a risk factor involved in various diseases. Permethrin, a member of the family of synthetic pyrethroids, is widely used as insecticide in agriculture and other domestic applications. To investigate possible cardiotoxicity, we had examined different concentrations of permethrin on the freshly isolated rat heart cells using the alkaline comet assay. A significant difference in % tail DNA between all concentrations of permethrin (5, 10, 20 microM) and vehicle (control) without enzymes and with Fpg-treated cells were measured. The results indicated that permethrin induced oxidative damage to purine bases in the heart cells. Pyrimidines oxidation was evaluated using Endonuclease III (Endo III), but the results did not reveal any significant changes. After permethrin exposure, cells were studied to evaluate their DNA repair capacity. A complete DNA repair at 10 and 20 microM was measured after 30 and 60 min of repair intervals. Significant change in plasma membrane fluidity at different depths of bilayer was measured following permethrin treatment. Membrane fluidity in the hydrophilic-hydrophobic region was reduced, while the hydrophobic inner resulted more fluid following permethrin treatment of heart cells. This work points to standardize conditions applicable to ex vivo cells following in vivo treatment in order to study the cardiotoxicity of insecticide. PMID- 20574785 TI - Response of predatory mites to a herbivore-induced plant volatile: genetic variation for context-dependent behaviour. AB - Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators' responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles. PMID- 20574786 TI - EGFL6 is increasingly expressed in human obesity and promotes proliferation of adipose tissue-derived stromal vascular cells. AB - With increasing rates of obesity driving the incidence of type 2 diabetes and cardiovascular diseases to epidemic levels, understanding of the biology of adipose tissue expansion is a focus of current research. Identification and characterization of secreted proteins of the adipose tissue could provide further insights into the function of adipose tissue and might help to therapeutically influence the development of obesity and associated metabolic disorders. In the present study, we identified human epidermal growth factor-like domain multiple-6 (EGFL6) as an adipose tissue-secreted protein. EGFL6 expression in human subcutaneous adipose tissue significantly increased with obesity and decreased after weight loss. Further, expression and secretion of EGFL6 increased with in vitro differentiation of human preadipocytes, suggesting that mature adipocytes are the main source of EGFL6. Containing epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) integrin binding motif and a mephrin, A5 protein and receptor protein-tyrosine phosphatase mu (MAM) domain, EGFL6 was suggested to be an extra-cellular matrix protein. Recombinant human EGFL6 protein mediated cell adhesion of human adipose tissue-derived stromal vascular cells (AD-SVC) in an RGD-dependent manner. FACS analyses revealed specific binding of the protein to the cell surface of AD-SVC with the binding being predominantly mediated by the EGF-like repeats. Recombinant EGFL6 enhanced proliferation of human AD-SVC as measured by MTS assay and [(14)C]-thymidine incorporation. These results indicate that human EGFL6 is a paracrine/autocrine growth factor of adipose tissue up regulated in obesity and potentially involved in the process of adipose tissue expansion and the development of obesity. PMID- 20574787 TI - Gastric leak after laparoscopic sleeve gastrectomy. AB - Sleeve gastrectomy is a recently developed technique for treating morbid obesity. Since it is a simple procedure, the number of surgeons using it has grown in recent years. The patients who present fistulas after surgery often undergo a harrowing postoperative period as well as increased morbidity and mortality. Our aim was to assess the incidence, causes, diagnosis, management, and prevention of leaks after sleeve gastrectomy. PMID- 20574788 TI - The role of exercise in the treatment of osteoporosis. AB - The objective of exercise in the treatment of osteoporosis is to improve axial stability through improvement of muscle strength. Therefore, a back extension exercise program specific to one's musculoskeletal competence and pain can be performed in a sitting position and later advanced to the prone position. When fragility is resolved, back extension is performed against resistance applied to the upper back. To decrease pain and immobility in acute vertebral fracture, use of spinal orthoses become inevitable. Therapeutic exercise should address osteoporosis-related deformities of axial posture, which can increase risk of fall and fracture. Strengthening of the major appendicular muscles decreases fragility. The effect of strengthening exercise is augmented by proper intake of cholecalciferol and calcium. Thus, the role of a therapeutic exercise program is to increase muscle strength safely, decrease immobility-related complications, and prevent fall and fracture. As with pharmacotherapy, therapeutic exercises are individualized. PMID- 20574789 TI - A phase I study of topotecan and gemcitabine in advanced solid tumors. AB - PURPOSE: Gemcitabine and topotecan are commonly used anti-tumor agents with a wide spectrum of activity in vitro and in vivo. A phase I trial of a combination of these two agents was initiated based on the premise that both gemcitabine and topotecan cause DNA damage and interfere with DNA repair by different mechanisms. Synergism has been demonstrated in vitro when gemcitabine and other topoisomerase I inhibitors have been combined. PATIENTS AND METHODS: Seventeen patients with advanced solid tumors signed consent and were treated on this study with at least one cycle. Treatment consisted of gemcitabine at doses of 400 to 625 mg/m(2) days 1 and 5 in combination with topotecan at doses of 0.8 to 1 mg/m(2) given on days 2 through 5 every 21 days. RESULTS: The dose limiting toxicities of granulocytopenia and thrombocytopenia were reached at the highest dose level of gemcitabine 625 mg/m(2) and topotecan 1 mg/m(2). A diffuse skin rash was also seen in four treated patients and responded well to treatment with steroids. One partial response and seven stable disease were seen as best response in 16 evaluable patients. CONCLUSION: The combination of gemcitabine and topotecan was found to be tolerable with interesting preliminary activity. The recommended phase II dose for this combination is gemcitabine at 500 mg/m(2) on days 1 and 5 with topotecan at 0.8 mg/m(2) on days 2 to 5. PMID- 20574790 TI - A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. AB - PURPOSE: The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. EXPERIMENTAL DESIGN: We performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative >=15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1. RESULTS: We enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced >= grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB. CONCLUSIONS: Single agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach. PMID- 20574791 TI - Endometriosis and infertility. AB - Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments. PMID- 20574792 TI - [Current medicinal treatment of metastasized colorectal carcinoma]. AB - Medical treatment of metastatic colorectal carcinoma has become more effective in recent years. In addition to an increasing number of cytotoxic drugs (e.g. fluoropyrimidines, irinotecan, oxaliplatin), monoclonal antibodies against VEGF or the EGF receptor have become available. These developments, combined with an increasing number of metastasectomies, have improved the prognosis of patients with metastatic colorectal cancer to a median survival of 24-30 months.Starting with the determination of K-RAS mutations the first molecular markers have found a place in the routine diagnostics i. e. to predict which patients have a higher chance (K-RAS wild type) or very low chance (K-RAS mutation) to respond to EGFR antibody treatment. This information complements important clinical factors for the choice of the therapeutic regimen, such as the treatment target (e.g. neoadjuvant treatment of non-resectable liver metastases), tumor symptoms which urgently require a tumor response and comorbidities. PMID- 20574793 TI - [Value of laparoscopic liver resection]. AB - Whereas in other fields of surgery minimally invasive techniques have replaced the open surgery approach, liver resection is still a domain of conventional surgery. However, it is internationally emerging that laparoscopic hepatic surgery will become more important by conceptional improvements. This article describes the technical aspects of laparoscopic liver resection, in particular the procedure with respect to the individual liver segments. The advantages and disadvantages of the minimally invasive technique and also the indications for laparoscopic liver resection will be discussed. PMID- 20574794 TI - Superior mesenteric artery embolism treated with percutaneous mechanical thrombectomy. AB - A case of acute superior mesenteric artery embolism treated with percutaneous thrombus aspiration is described. A 63-year-old man with chronic atrial fibrillation was admitted to the hospital with progressive abdominal pain. Computed tomography angiography revealed an occlusion of the distal part of the superior mesenteric artery. The patient was effectively treated using transaxillary percutaneous mechanical thrombectomy using a 6F Aspirex thrombectomy catheter. PMID- 20574795 TI - Initial experience of uterine fibroid embolization using porous gelatin sponge particles. AB - The purpose of this study was to prospectively assess the safety and effectiveness of uterine artery embolization (UAE) using porous gelatin particle (PGP; Gelpart; Asuterasu, Tokyo, Japan) for symptomatic uterine fibroids. Twenty five consecutive premenopausal women underwent UAE with PGP. The angiographic end point of embolization was near stasis of the ascending uterine artery. Pelvic magnetic resonance imaging (MRI) was obtained before and after the procedure. Complications were assessed. The outcomes of technique, infarction rates of all fibroid tissue after UAE with contrast-enhanced MRI, change in symptoms and quality of life using serial Uterine Fibroid Symptom and Quality of Life (UFS QOL) questionnaires, and additional interventions were evaluated. Bilateral UAE was successfully performed in all patients. Enhanced MRI 1 week after UAE showed that 100% infarction of all fibroid tissue was achieved in 65% (15 of 23) of patients; 90-99% infarction was achieved in 35% (8 of 23) of patients. Mean follow-up was 12 months (range 1-20). Symptom and QOL scores at baseline were 47.2 and 61.7, respectively. Both scores significantly improved to 26.3 (P<0.001) and 82.4 (P<0.001) at 4 months and to 20.4 (P<0.001) and 77.6 (P<0.001) at 1 year, respectively. No additional gynecologic interventions were performed in any patient. There were no major complications. Minor complications occurred in two patients. UAE using PGP is a safe and effective procedure and shows that outcomes after UAE, as measured with enhanced MRI and UFS-QOL questionnaires, seem comparable with those of UAE using other embolic agents. PGP is a promising embolic agent used for UAE to treat symptomatic uterine fibroids. Further comparative study between PGP and other established embolic agents is required. PMID- 20574796 TI - Cryoplasty versus conventional balloon angioplasty of the femoropopliteal artery in diabetic patients: long-term results from a prospective randomized single center controlled trial. AB - The purpose of this study was to investigate the immediate and long-term results of cryoplasty versus conventional balloon angioplasty in the femoropopliteal artery of diabetic patients. Fifty diabetic patients (41 men, mean age 68 years) were randomized to cryoplasty (group CRYO; 24 patients with 31 lesions) or conventional balloon angioplasty (group COBA; 26 patients with 34 lesions) of the femoropopliteal artery. Technical success was defined as <30% residual stenosis without any adjunctive stenting. Primary end points included technical success, primary patency, binary in-lesion restenosis (>50%), and freedom from target lesion recanalization. Cox proportional hazards regression analysis was performed to adjust for confounding factors of heterogeneity. In total, 61.3% (19 of 31) in group CRYO and 52.9% (18 of 34) in group COBA were de novo lesions. More than 70% of the lesions were Transatlantic Inter-Society Consensus (TASC) B and C in both groups, and 41.4% of the patients in group CRYO and 38.7% in group COBA suffered from critical limb ischemia. Immediate technical success rate was 58.0% in group CRYO versus 64.0% in group COBA (p = 0.29). According to 3-year Kaplan-Meier estimates, there were no significant differences with regard to patient survival (86.8% in group CRYO vs. 87.0% in group COBA, p = 0.54) and limb salvage (95.8 vs. 92.1% in groups CRYO and COBA, respectively, p = 0.60). There was a nonsignificant trend of increased binary restenosis in group CRYO (hazard ratio [HR] 1.3; 95% CI 0.6-2.6, p = 0.45). Primary patency was significantly lower in group CRYO compared with group COBA (HR 2.2; 95% CI 1.1-4.3, p = 0.02). Significantly more repeat intervention events because of recurrent symptoms were required in group CRYO (HR 2.5; 95% CI 1.2-5.3, p = 0.01). Cryoplasty was associated with lower primary patency and more clinically driven repeat procedures after long-term follow-up compared with conventional balloon angioplasty. PMID- 20574797 TI - Principal component vector rotation of the tongue color spectrum to predict "Mibyou" (disease-oriented state). AB - PURPOSE: Kampo medicine (Japanese traditional herbal medicine) contains concepts useful for preventive medicine. For example, "Mibyou" (disease-oriented state) aims to prevent illness by early recognition. Kampo diagnosis is based on subjective examinations, such as tongue inspection, by trained specialist physicians. An objective metric of the tongue color spectrum was developed as a surrogate for subjective visual inspection. METHODS: Tongue images were acquired with a hyperspectral imaging system, and the uncoated tongue region was segmented automatically. The spectral information of the uncoated tongue area was analyzed by principal component analysis (PCA). The component vector most representative of each clinical symptom was found by rotating the vector on a plane spanned by two arbitrary principal component vectors. RESULTS: The system was tested in human volunteers. Forty-four hyperspectral images were acquired from 30 healthy male subjects for initial testing. The Oketsu (blood stagnation) score was determined by an experienced clinician in Kampo medicine from 27 of 30 subjects. The correlation between respective principal components and Oketsu score was 0.67 at maximum, and increased to 0.73 by linear combination, while it was -0.75 by vector rotation. Significant correlations for many disorders were demonstrated, and vector rotation showed better correlation than linear combination. CONCLUSIONS: A PCA-based algorithm was developed to objectively evaluate patients using color images of the tongue surface. Testing showed that this method was a feasible surrogate for expert visual tongue analysis. This tool should help non trained people identify "Mibyou" health status for individuals. The algorithm is free of empirical criteria, and it may be it applicable to many hyperspectral image types. PMID- 20574798 TI - An algorithm for calculi segmentation on ureteroscopic images. AB - PURPOSE: The purpose of the study is to develop an algorithm for the segmentation of renal calculi on ureteroscopic images. In fact, renal calculi are common source of urological obstruction, and laser lithotripsy during ureteroscopy is a possible therapy. A laser-based system to sweep the calculus surface and vaporize it was developed to automate a very tedious manual task. The distal tip of the ureteroscope is directed using image guidance, and this operation is not possible without an efficient segmentation of renal calculi on the ureteroscopic images. METHODS: We proposed and developed a region growing algorithm to segment renal calculi on ureteroscopic images. Using real video images to compute ground truth and compare our segmentation with a reference segmentation, we computed statistics on different image metrics, such as Precision, Recall, and Yasnoff Measure, for comparison with ground truth. RESULTS: The algorithm and its parameters were established for the most likely clinical scenarii. The segmentation results are encouraging: the developed algorithm was able to correctly detect more than 90% of the surface of the calculi, according to an expert observer. CONCLUSION: Implementation of an algorithm for the segmentation of calculi on ureteroscopic images is feasible. The next step is the integration of our algorithm in the command scheme of a motorized system to build a complete operating prototype. PMID- 20574799 TI - Liver tumors segmentation from CTA images using voxels classification and affinity constraint propagation. AB - OBJECTIVE: We present a method and a validation study for the nearly automatic segmentation of liver tumors in CTA scans. MATERIALS AND METHODS: Our method inputs a liver CTA scan and a small number of user-defined seeds. It first classifies the liver voxels into tumor and healthy tissue classes with an SVM classification engine from which a new set of high- quality seeds is generated. Next, an energy function describing the propagation of these seeds is defined over the 3D image. The functional consists of a set of linear equations that are optimized with the conjugate gradients method. The result is a continuous segmentation map that is thresholded to obtain a binary segmentation. RESULTS: A retrospective study on a validated clinical dataset consisting of 20 tumors from nine patients' CTA scans from the MICCAI'08 3D Liver Tumors Segmentation Challenge Workshop yielded an average aggregate score of 67, an average symmetric surface distance of 1.76 mm (SD = 0.61 mm) which is better than the 2.0 mm of other methods on the same database, and a comparable volumetric overlap error (33.8 vs. 32.6%). The advantage of our method is that it requires less user interaction compared to other methods. CONCLUSION: Our results indicate that our method is accurate, efficient, and robust to wide variety of tumor types and is comparable or superior to other semi-automatic segmentation methods, with much less user interaction. PMID- 20574800 TI - Comparison of different grid of tags detection methods in tagged cardiac MR imaging. AB - PURPOSE: Non-invasive imaging assessment of cardiac function is important in cardiovascular disease diagnosis, especially for evaluation of local cardiac motion. Tagged cardiac MRI has been developed for this purpose, but evaluation of the results requires quantification and automation. METHODS: Two methods utilizing active contour modeling for wall motion extraction based on tagged cardiac MRI scans were evaluated based on properties of tracking methods in the image domain and frequency domain. Three criteria were used: accuracy, inter subject and intra-subject sensitivity. The tracking results were evaluated by a medical expert. The evaluation methodology and its possible generalization to other diagnostic methods were considered. RESULTS: Image domain and frequency domain analysis of tagged cardiac MRI data sets were evaluated demonstrating that the image domain method provides better results. The image domain method method is much more resistant to changes in the data, this time, due to a different subject being scanned. The frequency domain approach is not suitable for clinical applications, as the global error is significantly increased (more than 20%). CONCLUSION: The image domain method was found most effective, and it can generate a set of clearly identified parameters. The evaluation approach can be an interesting alternative to classical psychovisual studies which are time consuming and often fastidious for clinicians. PMID- 20574801 TI - Curettage and cryosurgery for low-grade cartilage tumors is associated with low recurrence and high function. AB - BACKGROUND: Chondrosarcomas of bone traditionally have been treated by wide or radical excision, procedures that may result in considerable lifelong disability. Grade 1 chondrosarcomas have little or no metastatic potential and are often difficult to distinguish from painful benign enchondromas. Curettage with adjuvant cryosurgery has been proposed as an alternative therapy for Grade 1 chondrosarcomas given the generally better function after the procedure. However, because it is an intralesional procedure, curettage and cryosurgery may be associated with higher rates of recurrence. QUESTIONS/PURPOSES: We asked whether Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery are associated with low recurrence rates and high functional scores. PATIENTS AND METHODS: We retrospectively reviewed the records of 46 patients with Grade 1 chondrosarcomas and enchondromas of uncertain malignant potential treated by curettage and cryosurgery. Forty-one patients had tumors of the long bones. Patients were followed a minimum of 18 months (average, 47.2. months; range, 18-134 months) for evidence of recurrence and for assessment of Musculoskeletal Tumor Society (MSTS) functional score. RESULTS: Two of the 46 patients had recurrences in the original tumor site (4.3% recurrence rate), which subsequently were removed by wide excision, and both patients were confirmed to be disease-free 36 and 30 months, respectively, after the second surgery. The mean MSTS score was 27.2 of 30 points (median, 29 points). CONCLUSIONS: Our observations show curettage with cryosurgery is associated with low recurrence of Grade 1 chondrosarcoma and high functional scores. Curettage with cryosurgery is a reasonable alternative to wide or radical excision as the treatment for Grade 1 chondrosarcomas, and allows for more radical surgery in the event of local recurrence. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 20574802 TI - Tranexamic acid reduces allogenic transfusion in revision hip arthroplasty. AB - BACKGROUND: Revision THA is associated with high blood loss and a high probability of blood transfusion in the perioperative period. In November 2003, government legislation established the Blood Utilization Program at our center to reduce the rate and risks associated with allogenic transfusion. QUESTIONS/PURPOSES: The purposes of this study were to (1) determine whether the allogenic transfusion rate in patients undergoing revision THA decreased in those who were reviewed preoperatively by the Blood Utilization Program versus those who were not; (2) determine whether tranexamic acid reduced the rate of transfusion; and (3) identify potential perioperative clinical parameters that are associated with an increased risk of blood transfusion. METHODS: We included all 159 patients who underwent revision THA from January 2006 to October 2008 having either a socket and/or femoral stem revision except those having only a liner exchange. One hundred and one patients attended the Blood Utilization Program preoperatively and 58 patients did not (ie, they required urgent/emergency surgery). RESULTS: The Blood Utilization Program referral made no difference in transfusion rate or transfusion amount; however, the transfusion rates and amount were decreased by 8% and one unit, respectively. In patients referred to the Blood Utilization Program, the intraoperative use of tranexamic acid (an antifibrinolytic) was associated with reduced transfusions, regardless of dosage; preoperative erythropoietin tended to reduce transfusions while preoperative oral iron supplements did not. CONCLUSIONS: To further increase the relevance of the blood utilization program, the guidelines for patients undergoing revision hip arthroplasty need to be redefined. LEVEL OF EVIDENCE: Level III, therapeutic study. See the guidelines online for a complete description of level of evidence. PMID- 20574803 TI - The internet and the physician-patient relationship. AB - BACKGROUND: Since the emergence of the public Internet in the early 1990s, the healthcare industry has been struggling to understand how best to utilize this resource. During the last decade there has been an increase in both the interest and participation by healthcare providers in the Internet space, but many observers continue to push for more development of healthcare resources to better support the provider-patient relationship. QUESTIONS/PURPOSES: This paper will review the historical development of the Internet, the core concepts that have driven the emergence and evolution of the Internet as a mass medium of information exchange, and how the healthcare industry can harness the Internet to improve the provider patient relationship. WHERE ARE WE NOW?: The healthcare industry continues to lag behind other industries that have been transformed by the Internet. Numerous industries including travel, real estate, retail sales, and banking have migrated both comprehensive information resources and transactions to the Internet in order to improve efficiency and customer satisfaction. That same process is occurring now in the healthcare industry. Credible and comprehensive Information resources are beginning to mature. Transactions are still in their infancy, reflecting a continued concern about privacy and security. WHERE DO WE NEED TO GO?: We need to improve information resources to educate and inform patients. Improving the availability and credibility of information resources will empower patients to make better healthcare decisions and I contend will ultimately reduce the cost of delivering care. HOW DO WE GET THERE?: Orthopaedists must first recognize the value of information resources to the patient. Effective communication with patients is a critical component of providing healthcare services. All healthcare providers should reflect on the importance of developing an effective communications strategy for their own practice and consider the benefits of participating in efforts by professional organizations to improve existing information resources. PMID- 20574804 TI - What is the midterm survivorship and function after hip resurfacing? AB - BACKGROUND: Hip resurfacing arthroplasty is a common procedure that improves functional scores and has a reported survivorship between 95% and 98% at 5 years. However, most studies are reported from the pioneering rather than independent centers or have relatively small patient numbers or less than five years followup. Various factors have been implicated in early failure. QUESTIONS/PURPOSES: Our purposes were to determine: (1) the midterm survival of the BHR; (2) the function in patients treated with hip resurfacing; and (3) whether age, gender, BMI, or size of components related to failure. METHODS: We reviewed the first 302 patients (329 hips) on whom we performed resurfacing arthroplasty. We assessed the survivorship, change in functional hip scores (HHS, OHS, WOMAC, UCLA), and analyzed potential risk factors (age, gender, BMI, component size) for failure. The mean age at the time of surgery was 56.0 years (range, 28.2-75.5 years). The minimum followup was 5 years (mean, 6.6 years; range, 5-9.2 years). RESULTS: Kaplan-Meier analysis showed survival of 96.5% (95% CI, 94.7-98.4) at 9 years taking revision for any cause as the endpoint. All functional hip scores (HHS, OHS, WOMAC, UCLA) improved. Survivorship was higher in men compared with women. The component sizes and body mass index were smaller in the revised group compared with the nonrevised group. CONCLUSIONS: Medium-term survivorship and functional scores of hip resurfacing are comparable to those from the pioneering center. Hip resurfacing remains a good alternative to THA, particularly in the younger male population with relatively large femoral head sizes. PMID- 20574805 TI - The peel in total knee revision: exposure in the difficult knee. AB - BACKGROUND: The femoral peel to expose a difficult knee was first described by Windsor and Insall in the mid-1980s. This surgical exposure consists of a complete soft tissue subperiosteal peel of the femur. It includes the detachment of the origin of the medial and lateral collateral ligaments. QUESTIONS/PURPOSES: We investigated the utility of a surgical exposure, the modified femoral peel, for total knee revision. METHODS: We retrospectively reviewed all 101 patients who had revision TKA (132 revisions) with the femoral peel technique from January 2000 to September 2007. Of the 101 patients, three patients died, eight patients were excluded, and three patients were lost to followup. Eighty-seven patients (116 procedures) met the inclusion criteria. Outcome measures assessed included Knee Society knee score, Knee Society function score, Hospital for Special Surgery knee score, complications, and number of reoperations. The minimum followup was 2 years (mean, 3.5 years; range, 2-9 years). RESULTS: Mean Knee Society knee scores improved from 47 to 85. Hospital for Special Surgery knee scores improved from 56 to 80. Quality of Well-Being and WOMAC all dimensions improved. Overall orthopaedic complication rate was 17%. Flexion contracture was improved. CONCLUSIONS: This surgical approach, which results in a complete soft tissue degloving of the distal femur and proximal tibia, allowed satisfactory exposure in all cases and the complication rate related to this exposure method was comparable with other series using diverse methods of knee exposure. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20574806 TI - Treatment based on the type of infected TKA improves infection control. AB - BACKGROUND: A classification system with four types of infected TKAs has been commonly used to determine treatment, especially with regard to whether the prosthesis should be removed or retained. QUESTIONS/PURPOSES: We asked whether (1) the classification-dictated treatment of the four types of infection after TKA would control infection and maintain functional TKA; (2) repeated debridement and two-stage TKA would further improve the infection control rate after initial treatment; and (3) fixation of TKA prosthesis to the host bone was achieved. METHODS: We retrospectively reviewed 114 patients with 116 infected TKAs. We determined the infection control rate after initial treatment, repeated debridement and two-stage TKA. We evaluated the functional and radiographic results using the Knee Society and Hospital for Special Surgery knee scoring systems. The minimum followup was 2 years (mean, 5.6 years; range, 2-8 years). RESULTS: The overall infection control rate was 100% in all patients. All patients with early superficial postoperative infection, 94% of patients with early deep postoperative infection, 96% of patients with late chronic infection, and 86% of patients with acute hematogenous infection maintained functioning knee prosthesis at the final followup. One hundred nine of the 114 patients could walk with no or only slight pain and maintained functioning knee prostheses. These 109 patients had stable fixation of the TKA prosthesis to host bone. CONCLUSIONS: The techniques proposed by the classification effectively controlled infection and maintained functional TKA with firm fixation of the TKA prosthesis in most patients. Repeated debridement and two-stage TKA further improved the control of infection and functional TKA after initial treatment. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 20574807 TI - Complex role of the HIF system in cardiovascular biology. AB - The hypoxia-inducible factor (HIF) system was discovered as an oxygen-sensitive regulatory pathway that confers adaptive responses to hypoxia. Novel aspects of this growing network indicate that there is a significant, nonhypoxic contribution to regulation. Multiple lines of evidence suggest that components of the HIF pathway are intimately involved in the pathogenesis of cardiovascular disorders. This review highlights the functional context of the HIF system in cardiovascular pathobiology with possible therapeutic implications. PMID- 20574808 TI - Mouse models of cancers: opportunities to address heterogeneity of human cancer and evaluate therapeutic strategies. AB - The heterogeneity of human breast cancer has been well described at the morphological, molecular, and genomic levels. This heterogeneity presents one of the greatest obstacles in the effective treatment of breast cancer since the distinct forms of breast cancer that reflect distinct mechanisms of disease will require distinct therapies. Although mouse models of cancer have traditionally been used to simplify the study of human disease, we suggest that there are opportunities to also model the complexity and heterogeneity of human cancer. Here, we illustrate the similarities of mouse models to the human condition in the heterogeneity of both pathologies and gene expression. We then provide an illustration of the potential of gene expression analysis methods when used in conjunction with current treatment options to model individualized therapeutic regimes. PMID- 20574809 TI - MIR152, MIR200B, and MIR338, human positional and functional neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis. AB - MicroRNAs (MIRs) perform critical regulatory functions within cell networks, both in physiology as well as in pathology. Through the positional gene candidate approach, we have identified three MIRs (MIR152, MIR200B, and MIR338) that are located in regions frequently altered in neuroblastoma (NB) and target mRNAs encoding proteins involved in cell proliferation, neuroblast differentiation, neuroblast migration, and apoptosis. Expression analysis in NB biopsies and NB cell lines showed that these MIRs are dysregulated. We have characterized a CpG island, close to the gene encoding MIR200B and hypermethylated in NB samples, that explains its negative regulation. Expression of MIR152, MIR200B, and MIR338 is specifically modulated in NB cell lines during differentiation and apoptosis. Functional genomic experiments through enforced expression of MIR200B and knockdown of MIR152 resulted in a significant decrease of the invasion activity of SH-SY5Y cells. Reconstruction of a NB network comprising MIR152, MIR200B, and MIR338 allowed us to confirm their role in the control of NB cell stemness and apoptosis: This suggests that altered regulation of these MIRs could have a role in NB pathogenesis by interfering with the molecular mechanisms, which physiologically control differentiation and death of neuroblasts. Accordingly, they could be considered as new NB biomarkers and potential targets of antagomirs or epigenetic therapies. PMID- 20574810 TI - Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. AB - The forkhead-box protein P3 (Foxp3) is a key transcription factor for the development and suppressive activity of regulatory T cells (Tregs), a T cell subset critically involved in the maintenance of self-tolerance and prevention of over-shooting immune responses. However, the transcriptional regulation of Foxp3 expression remains incompletely understood. We have previously shown that epigenetic modifications in the CpG-rich Treg-specific demethylated region (TSDR) in the Foxp3 locus are associated with stable Foxp3 expression. We now demonstrate that the methylation state of the CpG motifs within the TSDR controls its transcriptional activity rather than a Treg-specific transcription factor network. By systematically mutating every CpG motif within the TSDR, we could identify four CpG motifs, which are critically determining the transcriptional activity of the TSDR and which serve as binding sites for essential transcription factors, such as CREB/ATF and NF-kappaB, which have previously been shown to bind to this element. The transcription factor Ets-1 was here identified as an additional molecular player that specifically binds to the TSDR in a demethylation-dependent manner in vitro. Disruption of the Ets-1 binding sites within the TSDR drastically reduced its transcriptional enhancer activity. In addition, we found Ets-1 bound to the demethylated TSDR in ex vivo isolated Tregs, but not to the methylated TSDR in conventional CD4(+) T cells. We therefore propose that Ets-1 is part of a larger protein complex, which binds to the TSDR only in its demethylated state, thereby restricting stable Foxp3 expression to the Treg lineage. PMID- 20574811 TI - Vocational, social, and cognitive rehabilitation for individuals diagnosed with schizophrenia: a review of recent research and trends. AB - A growing body of evidence suggests that social and vocational interventions effectively enhance social and vocational functioning for individuals with schizophrenia. In this review, we first consider recent advances in vocational and social rehabilitation, then examine current findings on neurocognition, social cognition, and motivation with regard to the impact these elements have on rehabilitation interventions and outcomes. A critical evaluation of recent studies examining standalone treatment approaches and hybrid approaches that integrate components such as cognitive remediation and skills training reveals several ongoing challenges within the field. Greater understanding of the differential impact of various approaches, methods that may increase the magnitude of treatment effects, and the generalization of treatment effects to community functioning are among crucial areas for future research. Overall, these treatments hold promise in improving psychosocial functioning and helping individuals with schizophrenia acquire important life skills. PMID- 20574812 TI - Preoperative CT staging in sigmoid diverticulitis--does it correlate with intraoperative and histological findings? AB - PURPOSE: This study was designed to evaluate whether the computed tomography (CT) reflects the extent of the inflammation in sigmoid diverticulitis (SD) in order to draw conclusions for selecting the appropriate treatment. METHODS: Two hundred four patients who underwent resection for SD from January 2003 to December 2008 were included. The preoperative CT stage was compared with intraoperative and histological findings. Patients were classified into phlegmonous (Hansen-Stock IIa), abscess-forming (HS IIb), and free perforated (HS IIc) forms of SD. Patients with a recurrent type of diverticulitis were excluded. RESULTS: In the phlegmonous type (HS IIa; n = 75), we found a correlation with the preoperative stage in 52% (intraoperative) and 56% (histological), an understaging in 12% (intraoperative) and 11% (histological), and an overstaging in 36% (intraoperative) and 33% (histological). In the abscess-forming type (HS IIb, Hinchey I/II; n = 87), we found conformity in 92% (intraoperative) and 90% (histological), understaging in 3% (intraoperative) and 0% (histological), and overstaging in 5% (intraoperative) and 10% (histological). In the presence of a free perforation (HS IIc, Hinchey III/IV; n = 42), we saw conformity in 100% (intraoperative and histological). The positive predictive value for correctly diagnosing of phlegmonous type (HS IIa), abscess-forming type (HS IIb), and free perforation (HS IIc) by CT was intraoperatively (histologically) 52% (56), 92% (90), and 100% (100), respectively. CONCLUSIONS: The CT is one of the most accurate methods for staging in SD. However, in the phlegmonous type (HS IIa), it leads to an overestimation of the findings in every third patient. It must be clarified whether this pronounced low inflammation should really be regarded as a complicated form of SD. In contrast, the abscess-forming (HS IIb) and free perforated (HS IIc) type of complicated SD is very well reflected by CT. PMID- 20574813 TI - Significantly improved expression and biochemical properties of recombinant Serratia marcescens lipase as robust biocatalyst for kinetic resolution of chiral ester. AB - A lipase gene from Serratia marcescens ECU1010 was cloned into expression vector pET28a, sequenced, and overexpressed as an N terminus His-tag fusion protein in Escherichia coli. Through the optimization of culture conditions in shake flask, the lipase activity was improved up to 1.09 x 105 U/l, which is a great improvement compared to our previous reports. It was purified to homogeneity by Ni-NTA affinity chromatography with an overall yield of 59.4% and a purification factor of 2.4-fold. This recombinant lipase displayed excellent stability below 30 degrees C and within the pH range of 5.0-6.8, giving temperature and pH optima at 40 degrees C and pH 9.0, respectively. The lipase activity was found to increase in the presence of metal ions such as Ca2+, Cu2+, and some nonionic surfactants such as PEG series. In addition, among p-nitrophenyl esters of fatty acids with varied chain length, the recombinant lipase showed the maximum activity on p-nitrophenyl laurate (C12). Using racemic trans-3-(4'-methoxy phenyl)-glycidyl methyl ester [(+/-)-MPGM] as substrate, which is a key chiral synthon for production of diltiazem, a 50% conversion yield was achieved after 4 h in toluene-water (100 mM KPB phosphate buffer, pH 7.5) biphasic system (5:5 ml) at 30 degrees C under shaking condition (160 rpm), affording (-)-MPGM in nearly 100% ee. The K(m) and V(max) values of the lipase for (+/-)-MPGM were 222 mM and 1.24 mmol min-1 mg-1, respectively. The above-mentioned features make the highly enantioselective lipase from Serratia marcescens ECU1010 a robust biocatalyst for practical use in large-scale production of diltiazem intermediate. PMID- 20574814 TI - Structure determination of proteins in 2H2O solution aided by a deuterium decoupled 3D HCA(N)CO experiment. AB - We developed an NMR pulse sequence, 3D HCA(N)CO, to correlate the chemical shifts of protein backbone (1)Halpha and (13)Calpha to those of (13)C' in the preceding residue. By applying (2)H decoupling, the experiment was accomplished with high sensitivity comparable to that of HCA(CO)N. When combined with HCACO, HCAN and HCA(CO)N, the HCA(N)CO sequence allows the sequential assignment using backbone (13)C' and amide (15)N chemical shifts without resort to backbone amide protons. This assignment strategy was demonstrated for (13)C/(15)N-labeled GB1 dissolved in (2)H(2)O. The quality of the GB1 structure determined in (2)H(2)O was similar to that determined in H(2)O in spite of significantly smaller number of NOE correlations. Thus this strategy enables the determination of protein structures in (2)H(2)O or H(2)O at high pH values. PMID- 20574815 TI - A controlled study of risk factors for disease and current problems in long-term testicular cancer survivors. AB - INTRODUCTION: To compare risk factors for disease and current problems in long term testicular cancer survivors (TCSs) and age-matched population-based controls (NORMs). METHODS: The study was cross-sectional and concerned 1,291 Norwegian TCSs followed up after a mean of 11 years, and 6,455 NORMs. Both TCSs and NORMs completed questionnaires and had a clinical examination. Indices for risk factors and current problems were calculated. Outcome measures were: visits to general practitioners last year, poor self-rated health, and poor quality of life (QoL). RESULTS: The mean risk score was significantly lower and the mean current problem score significantly higher in TCSs compared to NORMs without reaching clinical significance. The risk for future fatal cardiac events did not differ between the groups. TCSs had a higher risk for visiting a general practitioner than NORMs (OR 3.58, 95% CI 3.09-4.15), while no significant difference was observed for self rated health. Poor QoL in TCSs was significantly associated with more current problems than risk factors. Previous treatment for mental problems, presence of severe somatic disease and musculo-skeletal problems were significantly associated with all three outcome measures. Musculo-skeletal problems were most strongly associated with visits to general practitioners among TCSs. CONCLUSIONS: Several risk factors for preventive clinical interventions and current problems that eventually should be treated were identified in TCSs. IMPLICATIONS FOR CANCER SURVIVORS: TCSs show several risk factors and current problems that are relevant for visits to general practitioners, poorer self-rated health, and poorer QoL. These should get attention from health personnel caring for TCSs. PMID- 20574816 TI - Fish oil and antipsychotic drug risperidone modulate oxidative stress in PC12 cell membranes through regulation of cytosolic calcium ion release and antioxidant system. AB - Oxidative stress is a critical route of damage in various psychological disorders such as schizophrenia, although fish oil and risperidone (RISP) induce antioxidant effects in the human body. However, the mechanisms behind these effects remain elusive. We investigated the effects of fish oil and RISP in the PC12 cell line by evaluating Ca(2+) mobilization, lipid peroxidation (LP) and antioxidant levels. PC12 cells were divided into eight flasks: control, fish oil, RISP, H(2)O(2), fish oil + H(2)O(2), RISP + H(2)O(2), fish oil + RISP and fish oil + RISP + H(2)O(2). Cells were incubated with fish oil and RISP for 24 and 48 h, respectively. Then, cells were exposed to H(2)O(2) for 15 min before analysis. Ca(2+) release and LP levels were higher in the H(2)O(2) group than in the control, RISP and fish oil groups, although their levels were decreased by incubation of cells in fish oil and RISP. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in the H(2)O(2) group than in the control, RISP and fish oil groups, although levels were higher in cells incubated with fish oil and RISP than in those in the H(2)O(2) groups. In conclusion, these results indicate that RISP and fish oil induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) release and antioxidant levels. PMID- 20574817 TI - Effects of breed type and age at first calving on length of productive life in a cow-calf system in Southeastern Mexico. AB - The effect of age at first calving (AFC) and breed type (BG) on cow length of productive life in the herd (LPL) and cumulative kilograms of calves weaned per cow (KWC) was studied. Data on 313 Brahman, 183 Nellore, and 269 crossbred cows (undefined crosses of European * Zebu cattle) born from 1986 to 2002 were used. Three hundred and ninety-one out of the 765 cows had non-censored data. LPL curves by BG and AFC (<2.5, 2.5 to <3, 3 to <3.5, and >= 3.5 years of age) were obtained using life table procedures. The magnitude of the effect of AFC and BG on LPL was determined using Cox proportional hazard regression procedures. KWC data (n=359) were analyzed by a linear model that included the effects of period of birth of the cow (in years), BG, and AFC. There was no difference in the survival curves between BG (p>0.05), but there was for the hazard ratio of culling (p<0.05). Brahman and Nellore cows produced more kilograms of calves (p<0.05) than crossbred cows. AFC influenced LPL (p=0.014) and KWC (p=0.012). Cows with AFC <3 years of age stayed longer in the herd and weaned more KWC than those with a higher AFC (p<0.05). PMID- 20574818 TI - Determinants of choice of market-oriented indigenous Horo cattle production in Dano district of western Showa, Ethiopia. AB - Based on a survey data collected from 150 farming households in Dano district of western Showa of Ethiopia, this paper analyzes determinants of smallholders' choice for market oriented indigenous Horo cattle production and tries to suggest policy alternatives for sustainable use of animal genetic resource in the study area. Descriptive statistics and binary logistic model were employed to analyze the data. Eight explanatory variables including age of the household head, size of the grazing land, total size of cultivated land, farmer's experience in indigenous cattle production, farmer's attitude towards productivity of local breed, off-farm income, fattening practice, and availability of information and training of the head of the household regarding conservation, management and sustainable use indigenous cattle were found to be statistically significant variables to explain farmers' choice for market oriented indigenous cattle production activities. Besides, possible policy implications were made in order to improve conservation, management and sustainable use of market oriented indigenous cattle genetic resources. PMID- 20574819 TI - Coprological prevalence and intensity of helminth infection in working horses in Lesotho. AB - This study aimed to (1) estimate infection prevalence of strongyle, Oxyuris equi and Parascaris equorum species and the intensity of infection with strongyles in working horses in lowland Lesotho and (2) investigate associations between infection and horse age, sex and owner-reported use of anthelmintics. In a cross sectional survey, fresh faecal samples were obtained from 305 randomly selected horses and worm egg counts performed using a validated field laboratory kit. Details of anthelmintic use were collected using a standardised face-to-face owner questionnaire. Infection prevalence estimates for each species were calculated, as were infection intensity estimates for strongyle species. Logistic regression was used to investigate associations between exposure variables and infection status/intensity. Prevalence of strongyle infection was 88.2%; 11.8% of horses were not infected and infection intensity was low (1-500 eggs per gram (epg)) in 19.7%, medium (501-1,000 epg) in 19.7%) and high (>1,001 epg) in 48.8%. Decreasing strongyle infection intensity was associated with the use of proprietary equine anthelmintic products (OR 0.18, 95%CI 0.11-0.30, p<0.0001). Prevalence of O. equi infection was 6.2%; the odds of infection with this parasite decreased with increasing horse age (OR 0.84, 95%CI 0.72-0.97, p = 0.02). P. equorum infection prevalence was 21.6%; no statistically significant associations with the investigated exposure variables were found. In conclusion, strongyle infection is endemic in working horses in lowland Lesotho, but proprietary equine anthelmintics assist in managing infection. The apparent lack of age-acquired immunity to P. equorum infection may deserve further investigation. Although O. equi infection is less widespread, measures to protect younger animals may be appropriate. PMID- 20574820 TI - A high throughput microelectroporation device to introduce a chimeric antigen receptor to redirect the specificity of human T cells. AB - It has been demonstrated that a chimeric antigen receptor (CAR) can directly recognize the CD19 molecule expressed on the cell surface of B-cell malignancies independent of major histocompatibility complex (MHC). Although T-cell therapy of tumors using CD19-specific CAR is promising, this approach relies on using expression vectors that stably integrate the CAR into T-cell chromosomes. To circumvent the potential genotoxicity that may occur from expressing integrating transgenes, we have expressed the CD19-specific CAR transgene from mRNA using a high throughput microelectroporation device. This research was accomplished using a microelectroporator to achieve efficient and high throughput non-viral gene transfer of in vitro transcribed CAR mRNA into human T cells that had been numerically expanded ex vivo. Electro-transfer of mRNA avoids the potential genotoxicity associated with vector and transgene integration and the high throughput capacity overcomes the expected transient CAR expression, as repeated rounds of electroporation can replace T cells that have lost transgene expression. We fabricated and tested a high throughput microelectroporator that can electroporate a stream of 2 x 10(8) primary T cells within 10 min. After electroporation, up to 80% of the passaged T cells expressed the CD19-specific CAR. Video time-lapse microscopy (VTLM) demonstrated the redirected effector function of the genetically manipulated T cells to specifically lyse CD19+ tumor cells. Our biomedical microdevice, in which T cells are transiently and safely modified to be tumor-specific and then can be re-infused, offers a method for redirecting T-cell specificity, that has implications for the development of adoptive immunotherapy. PMID- 20574822 TI - Multiple copies of SRY on the large Y chromosome of the Okinawa spiny rat, Tokudaia muenninki. AB - The Okinawa spiny rat, Tokudaia muenninki, is the only species with a Y chromosome in the genus Tokudaia. Its phylogenic relationship with two XO/XO species, Tokudaia osimensis and Tokudaia tokunoshimensis, lacking a Y chromosome and the mammalian sex-determining gene SRY, is unknown. Furthermore, there has been little cytogenetic analysis of the sex chromosomes in T. muenninki. Therefore, we constructed molecular phylogenetic trees with nucleotide sequences of cyt b, RAG1, and IRBP. All trees strongly supported that T. muenninki was the first to diverge from the Tokudaia ancestor, indicating that loss of the Y chromosome and SRY occurred in the common ancestor of the two XO/XO species after T. muenninki diverged. We found that the X and Y chromosomes of T. muenninki consisted of large euchromatic and heterochromatic regions by conducting G- and C banding analyses. PCR, Southern blotting, and FISH revealed that T. muenninki males had multiple SRY copies on the long arm of the Y chromosome. At least three of 24 SRY sequences contained a complete open reading frame (ORF). A species specific substitution from alanine to serine was found in all copies at the DNA binding surface within the HMG-box, suggesting that it occurred in an original SRY. PMID- 20574821 TI - Role of ERG1 isoforms in modulation of ERG1 channel trafficking and function. AB - The 'ether-a-go-go-related' gene type 1 (ERG1 or Kv11.1) protein is the product of the KCNH2 gene. Currents generated by ERG1 channels are important in a range of tissues including neuronal, smooth muscle, and cardiac tissues, as well as in cancer cells. There are five known isoforms of the ERG1 protein. Overlapping patterns of endogenous expression of ERG1 isoforms have been described in several tissue types. Abnormal changes in the relative abundance of ERG1 isoforms may result in disease. Recent studies have suggested that the different isoforms play a prominent role in expression and trafficking of ERG1 channels as well as in modulating the electrophysiological properties of the channels. This review focuses on the differences between the ERG1 isoforms and describes the physiological implications thereof. It is described how changes in the relative expression level of the isoforms may have significant physiological consequences by modulation of tissue excitability. Additionally, the review proposes a standardized nomenclature of ERG1 isoforms based on their structural features. PMID- 20574823 TI - Characterisation of the chromosome fusions in Oreochromis karongae. AB - Oreochromis karongae, one of the "chambo" tilapia species from Lake Malawi, has a karyotype of 2n = 38, making it one of the few species investigated to differ from the typical tilapia karyotype (2n = 44). The O. karongae karyotype consists of one large subtelocentric pair of chromosomes, four medium-sized pairs (three subtelocentric and one submetacentric) and 14 small pairs. The five largest pairs could be distinguished from each other on the basis of size, morphology and a series of fluorescence in situ hybridisation (FISH) probes. The largest pair is easily distinguished on the basis of size and a chromosome 1 (linkage group 3) bacterial artificial chromosome (BAC) FISH probe from Oreochromis niloticus. BAC clones from O. niloticus chromosome 2 (linkage group 7) hybridised to one of the medium-sized subtelocentric chromosome pairs (no. 5) of O. karongae, distinguishing the ancestral medium-sized pair from the three other medium-sized chromosome pairs (nos. 2, 3 and 4) that appear to have resulted from fusions. SATA repetitive DNA hybridised to the centromeres of all 19 chromosome pairs and also revealed the locations of the relic centromeres in the three fused pairs. Telomeric (TTAGGG)(n) repeats were identified in the telomeres of all chromosomes, and an interstitial telomeric site (ITS) was identified in three chromosomal pairs (no. 2, 3 and 4). Additionally, two ITS sites were identified in the largest chromosome pair (pair 1), confirming the origin of this chromosome from three ancestral chromosomes. SATA and ITS sites allowed the orientation of the fusions in pairs 2, 3 and 4, which all appear to have been in different orientations (q-q, p-q and p-p, respectively). One of these fusions (O. karongae chromosome pair no. 2) involves a small chromosome (equivalent to linkage group 1), which in O. niloticus carries the main sex-determining gene. 4',6-Diamidino-2 phenyloindole staining of the synaptonemal complex in male O. karongae revealed the presumptive positions of the kinetochores, which correspond well to the centromeric positions observed in the mitotic karyotype. PMID- 20574824 TI - Occurrence and identification of yeast species in fermented liquid feed for piglets. AB - The major objective of the present study was to investigate the occurrence and identity of yeast species in fermented liquid feed (FLF) used for feeding piglets. In total, 40 different Danish farms were included in the analysis. The preparation and composition of FLF was found to be very heterogeneous with high variations in both yeast counts and yeast species composition. The yeast population varied between 6.0 * 10(3) and 4.2 * 10(7) cfug(-1) with an average yeast count of 8.7 * 10(6) +/- 1.1 * 10(7) cfug(-1). A total of 766 yeasts were isolated and identified by conventional and/or molecular typing techniques. The predominant yeast species in the FLF samples were found to be Candida milleri (58.4%), Kazachstania exigua (17.5%), Candida pararugosa (6.40%) and Kazachstania bulderi (5.09%). No clear separation between isolates of C. milleri and Candida humilis could be obtained based on sequencing of the D1/D2 region of the 26S rRNA gene. The combined use of ITS-RFLP analysis and phenotypic criteria did meanwhile suggest a closer relationship with C. milleri than C. humilis. PMID- 20574825 TI - Prediction of plausible bacterial composition based on terminal restriction fragment length polymorphisms using a Monte Carlo method. AB - We have developed a new approach for the estimation of bacterial proportional compositions in microbiota based on terminal restriction length polymorphism (T RFLP) data and a Monte Carlo algorithm. This program estimates proportional compositions by minimizing distances between peak values and the relative abundance of each group, containing several species, estimated from peak areas of capillary electrophoresis for T-RFLP analysis. Oral bacteria in 36 saliva samples obtained from three individuals were analyzed using the program. Upon comparison, the estimated proportional composition obtained from one of the samples matched that from a clone library. Additionally, comparisons among the bacterial proportional compositions of saliva samples obtained from three individuals four times per day for 3 days revealed that the types of microbiota present in each individual did not change within each 24-h time period and were distinguishable from those in other individuals. PMID- 20574826 TI - Amazonian anthrosols support similar microbial communities that differ distinctly from those extant in adjacent, unmodified soils of the same mineralogy. AB - We compared the microbial community composition in soils from the Brazilian Amazon with two contrasting histories; anthrosols and their adjacent non anthrosol soils of the same mineralogy. The anthrosols, also known as the Amazonian Dark Earths or terra preta, were managed by the indigenous pre Colombian Indians between 500 and 8,700 years before present and are characterized by unusually high cation exchange capacity, phosphorus (P), and calcium (Ca) contents, and soil carbon pools that contain a high proportion of incompletely combusted biomass as biochar or black carbon (BC). We sampled paired anthrosol and unmodified soils from four locations in the Manaus, Brazil, region that differed in their current land use and soil type. Community DNA was extracted from sampled soils and characterized by use of denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism. DNA bands of interest from Bacteria and Archaea DGGE gels were cloned and sequenced. In cluster analyses of the DNA fingerprints, microbial communities from the anthrosols grouped together regardless of current land use or soil type and were distinct from those in their respective, paired adjacent soils. For the Archaea, the anthrosol communities diverged from the adjacent soils by over 90%. A greater overall richness was observed for Bacteria sequences as compared with those of the Archaea. Most of the sequences obtained were novel and matched those in databases at less than 98% similarity. Several sequences obtained only from the anthrosols grouped at 93% similarity with the Verrucomicrobia, a genus commonly found in rice paddies in the tropics. Sequences closely related to Proteobacteria and Cyanobacteria sp. were recovered only from adjacent soil samples. Sequences related to Pseudomonas, Acidobacteria, and Flexibacter sp. were recovered from both anthrosols and adjacent soils. The strong similarities among the microbial communities present in the anthrosols for both the Bacteria and Archaea suggests that the microbial community composition in these soils is controlled more strongly by their historical soil management than by soil type or current land use. The anthrosols had consistently higher concentrations of incompletely combusted organic black carbon material (BC), higher soil pH, and higher concentrations of P and Ca compared to their respective adjacent soils. Such characteristics may help to explain the longevity and distinctiveness of the anthrosols in the Amazonian landscape and guide us in recreating soils with sustained high fertility in otherwise nutrient-poor soils in modern times. PMID- 20574827 TI - Battling in the trenches: case managers' ability to combat the effects of mental illness stigma on consumers' perceived quality of life. AB - Intervention effectiveness research requires that investigators include "real world" variables in the design of studies to develop an understanding of how interventions perform in the "real world." Two areas that have been neglected in effectiveness research on mental health case management are mental illness self stigma and the effects of different case managers. Self-stigma is a reality for many consumers that negatively impacts their lives. Case managers, themselves, are a potential source of autocorrelation and likely provide services differently. This study explores the relationship between self-stigma and quality of life for consumers receiving services from different case managers. Cross sectional data were collected from 160 consumers of an urban case management agency. Self-stigma was negatively associated with quality of life. Case managers did not account for a significant amount of variance in quality of life scores. However, the interaction between case manager and self-stigma was significant. Some case managers were able to mitigate the negative effects of self-stigma on quality of life. Future effectiveness research in community mental health case management needs to account for the effects of self-stigma, case managers, and the interaction between the two in the research design. PMID- 20574829 TI - Expression and single-step purification of mercury transporter (merT) from Cupriavidus metallidurans in E. coli. AB - The mercury transporter, merT, from Cupriavidus metallidurans was cloned into pRSET-C and expressed in various E. coli hosts. Expression of merT gene failed in common expression hosts like E. coli BL21(DE3), E. coli BL21(DE3)pLysS and E. coli GJ1158 due to expression induced toxicity. The protein was successfully expressed in E. coli C43(DE3) as inclusion bodies. The inclusion bodies were solubilized with Triton X-100 detergent. The detergent solubilized protein with N terminal His-tag was purified in a single-step by immobilized metal affinity chromatography with a yield of 8 mg l(-1). PMID- 20574828 TI - A pheromone to behave, a pheromone to learn: the rabbit mammary pheromone. AB - Birth is part of a continuum and is a major developmental change. Newborns need to adapt rapidly to the environment in terms of physiology and behaviour, and ability to locate the maternal source of milk is vital. Mechanisms have evolved resulting in the emission of olfactory cues by the mother and the processing of these cues by the young. Here, we focus on some sensory, cognitive and behavioural strategies developed by the European rabbit (Oryctolagus cuniculus) that optimize the early development of offspring. In this species, chemosensory communication between the mother and young plays a critical role in eliciting adaptive neonatal responses. In particular, lactating females release a molecule, the mammary pheromone, which has several functional impacts. It triggers orocephalic responses involved in the quick localization of nipples and sucking. Moreover, this unconditioned signal promotes rapid appetitive learning of novel odorants, acting as a potent organizer of neonatal cognition. The mammary pheromone-induced odour memory requires consolidation/reconsolidation processes to be maintained in the long term. Finally, as this mode of conditioning also promotes learning of mixtures of odorants, it supports investigations related to the capacity of neonatal olfaction to extract biological value from the complex environment. PMID- 20574830 TI - Use of the pyrG gene as a food-grade selection marker in Monascus. AB - Ma-pyrG was cloned from Monascus aurantiacus AS3.4384 using degenerate PCR with primers designed with an algorithm called CODEHOP, and its complete sequence was obtained by a PCR-based strategy for screening a Monascus fosmid library. Ma-pyrG encodes orotidine-5'-phosphate decarboxylase (OMPdecase), a 283-aminoacid protein with 81% sequence identity to that from Aspergillus flavus NRRL 3357. A pyrG mutant strain from M. aurantiacus AS3.4384, named UM28, was isolated by resistance to 5-fluoroorotic acid after UV mutagenesis. Sequence analysis of this mutated gene revealed that it contained a point mutation at nucleotide position +220. Plasmid pGFP-pyrG, bearing the green fluorescent protein gene (GFP) as a model gene and Ma-pyrG as a selection marker, were constructed. pGFP-pyrG were successfully transformed into UM28 by using the PEG method. PMID- 20574831 TI - Functional expression and magnetic nanoparticle-based Immobilization of a protein engineered marine fish epoxide hydrolase of Mugil cephalus for enantioselective hydrolysis of racemic styrene oxide. AB - A triple-point mutated fish microsomal epoxide hydrolase (mEH) gene from Mugil cephalus was expressed in Escherichia coli in the presence of various chaperones to prevent protein aggregations. The enantioselective hydrolytic activity was more than doubled by co-expressing the EH mutant gene with pGro7 plasmid. The highly active EH mutant with a his-tag was immobilized onto magnetic silica assembled with NiO nanoparticles. The immobilized mEH mutant was re-used more than 10 times with less than 10% activity loss. (S)-Styrene oxide with 98% enantiopurity was repeatedly obtained with over 50% of the theoretical yield by the magnetically separable high-performance mEH mutant. PMID- 20574832 TI - Efficient synthesis of 6-O-palmitoyl-1,2-O-isopropylidene-alpha-D-glucofuranose in an organic solvent system by lipase-catalyzed esterification. AB - In order to synthesize a sugar ester at high concentration, 1,2-O-isopropylidene alpha-D-glucofuranose (IpGlc), which is one of the sugar acetals and is more hydrophobic than unmodified glucose, was esterified with palmitic acid at 40 degrees C using immobilized lipase from Candida antarctica in some organic solvents or their mixtures. Acetone + t-butyl alcohol (3:1 v/v) improved both the initial reaction rate and yield after 80 h: the product reached its maximum value (240 mmol/kg solvent; ca. 110 g/kg solvent) when 400 mmol IpGlc/kg solvent and 1,200 mmol palmitic acid/kg solvent were used in this solvent mixture. PMID- 20574833 TI - Applicability of Penicillium chrysogenum rheological correlations to broths of other fungal strains. AB - Existing correlations of Power law consistency index with Penicillium chrysogenum biomass concentration and morphology were revised using a microscope magnification of 50 times to characterize the latter, rather than the 80 times used previously. This allowed tests of the correlations on broths of Aspergillus oryzae and Aspergillus niger, which have such large mycelial sizes that a lower magnification is required for accurate morphological analysis. The new correlations were successful at predicting the rheology of A. oryzae broths but not A. niger broths, which may be because of a change in the exponent on the biomass concentration in the correlations for the latter. Because the mean maximum dimension of clumps is magnification independent, the preferred correlation was K = C2m x [4 x 10-5D - 9 x 10-4] where K is the consistency index (Pa s(n)), C(m) is the biomass concentration as dry cell weight (g l(-1)) and D is the mean maximum dimension (MUm). PMID- 20574834 TI - Linear dynamic range for signal detection in fluorescent differential display. AB - We have determined the linear dynamic range in signal detection by Fluorescent Differential Display (FDD) using conditionally induced mRNA expression of the p53 tumor-suppressor gene as a control. By serial spiking of p53-induced RNA into that of non-induced RNA, we were able to quantitatively measure up to 100-fold change in p53 mRNA expression level. The linear dynamic range of signal detection per mRNA message was determined to be from 1000 up to 20,000 in fluorescence signal, in which the signals for the majority of mRNAs reside. Thus, FDD can be used to accurately quantify differences in mRNA expression among eukaryotic cells. PMID- 20574835 TI - Hyperosmolarity enhances transient recombinant protein yield in Chinese hamster ovary cells. AB - The effect of hyperosmolarity on transient recombinant protein production in Chinese hamster ovary (CHO) cells was investigated. Addition of 90 mM NaCl to the production medium ProCHO5 increased the volumetric yield of recombinant antibody up to 4-fold relative to transfection in ProCHO5 alone. Volumetric yields up to 50 mg l(-1) were achieved in a 6 day batch culture of 3 l. In addition, hyperosmolarity reduced cell growth and increased cell size. The addition of salt to cultures of transiently transfected CHO cells is a simple and cost-effective method to increase TGE yields in this host. PMID- 20574836 TI - Selection of Saccharomyces cerevisiae strains for efficient very high gravity bio ethanol fermentation processes. AB - An optimized very high gravity (VHG) glucose medium supplemented with low cost nutrient sources was used to evaluate bio-ethanol production by 11 Saccharomyces cerevisiae strains. The industrial strains PE-2 and CA1185 exhibited the best overall fermentation performance, producing an ethanol titre of 19.2% (v/v) corresponding to a batch productivity of 2.5 g l(-1) h(-1), while the best laboratory strain (CEN.PK 113-7D) produced 17.5% (v/v) ethanol with a productivity of 1.7 g l(-1) h(-1). The results presented here emphasize the biodiversity found within S. cerevisiae species and that naturally adapted strains, such as PE-2 and CA1185, are likely to play a key role in facilitating the transition from laboratory technological breakthroughs to industrial-scale bio-ethanol fermentations. PMID- 20574837 TI - The DNA-induced protective immunity with chicken interferon gamma against poultry coccidiosis. AB - The immunogenicity of Eimeria acervulina cSZ-2 and chicken interferon gamma was observed against Eimeria tenella challenge. The chickens were randomly divided into six groups of 24 chicks each. Three groups of chickens were injected with DNA vaccines pVAX1-cSZ2, pVAX1-chIFN-gamma and pVAX1-cSZ2-chIFN-gamma two times (at days 14 and 21) at a dose of 100 microg intramuscularly. Three other groups were kept as control and injected with TE buffer (10 mM Tris-HCl pH 7.6 and 1 mM EDTA). One week following the booster dose, all chickens except the non-infected, non-vaccinated control group were inoculated orally with 5 x 10(4) sporulated oocysts of E. tenella. Seven days post challenge, all chickens were weighted and slaughtered for cecal lesion scoring and oocyst counts. The results demonstrated that cSZ-2 in combination with interferon gamma can protect chickens from coccidiosis by significantly decreasing body weight loss and oocyst excretion reflecting partial protection against E. tenella infection, and further studies are necessary to test for protection against other Eimeria species. PMID- 20574838 TI - Wnt4, the first member of the Wnt family identified in Schistosoma japonicum, regulates worm development by the canonical pathway. AB - The Wnt signaling pathway is an evolutionarily conserved signal transduction pathway used extensively during animal development. We aim, by increasing our understanding of the Wnt signaling pathway, to find a key gene or protein present in schistosomes that can be developed into vaccine candidate or drug target. We therefore isolated the Wnt4 gene from Schistosoma japonicum. Wnt4 encodes a putative protein of 558 amino acids which contains the conserved functional domain of the Wnt gene family. We suppressed the expression of Wnt4 mRNA in 10 day schistosomulae by RNA interference. Quantitative PCR analysis showed that Wnt4 displayed a 73% reduction in the transcript level. And GSK-3beta and beta catenin, which are involved in Wnt canonical pathway, showed a 45% and 39% reduction in mRNA levels, respectively. PLC, CaMKII, DVL, and JNK, which are involved in Wnt non-canonical pathway, showed no reduction. These results suggest that the Wnt4 signal protein in S. japonicum regulates downstream genes by a canonical pathway. Wnt4 is the first member of the Wnt family to be identified in S. japonicum. An increased understanding of the Wnt signal transduction pathway will allow us to elucidate further the molecular mechanism of development in schistosomes. PMID- 20574839 TI - Identity concept learning in matching-to-sample tasks by tufted capuchin monkeys (Cebus apella). AB - The abstract concept of equivalence is considered one of the bases of higher order cognition, and it has been the subject of considerable research in comparative cognition. This study examined the conditions under which tufted capuchin monkeys (Cebus apella) are able to acquire an identity concept. Six capuchin monkeys were trained to solve a visual matching-to-sample (MTS) task on the basis of perceptual identity. The acquisition of the identity rule was inferred from the subject's ability to solve transfer tests with novel stimuli. We evaluated the ability of the capuchin monkeys to match the shape of novel stimuli after training with both several small stimulus sets (Experiment 1) and a large stimulus set (Experiment 2). Moreover, we examined the ability of capuchins to transfer the concept to novel visual dimensions, such as colour and size and to transfer to novel spatial arrangements of the stimuli (Experiment 2). We demonstrated that the ability of capuchins to match novel stimuli was improved by increasing the number of stimuli used during training (Experiments 1 and 2) and that after a widely applicable identity concept based on the stimulus shape was acquired, the capuchins were able to match stimuli according to an identity rule based on both the colour and size of the stimuli and when the spatial arrangement of the stimuli was varied (Experiment 2). This study is the first to demonstrate that the size of the training set affects the acquisition of an abstract identity concept in an MTS task in non-human primates. PMID- 20574840 TI - Histological examination of experimentally infected root canals after preparation by Er:YAG laser irradiation. AB - The influence of Er:YAG laser irradiation on periodontal tissues along the root surface and apical region during root canal preparation was histologically evaluated using experimentally infected root canals of rats. Eighty experimentally mesial infected root canals of mandibular first molars in rats were divided into four groups. In three groups, root canals were irradiated using an Er:YAG laser at 2 Hz with 34, 68, or 102 mJ/pulse for 30 s. Non-irradiated canals served as controls. The influence of laser irradiation on periodontal tissues along the root surface and apical area was evaluated histologically under light microscopy at 0 (immediately after), 1, 2, 4, and 8 weeks after irradiation. At all periods, no inflammation or resorption on the root surfaces caused by laser irradiation was observed in any cases in the control or 34 mJ/pulse-irradiated groups. However, mild to severe inflammation with resorption of root surfaces was observed in some cases in the 68- and 102-mJ/pulse irradiated groups. No significant difference was apparent between control and laser-irradiated groups at the apical area for all experimental periods (p > 0.05). These results suggest that thermal influences on periodontal tissues of experimentally infected root canals during root canal preparation by Er:YAG laser irradiation are minimal if appropriate parameters are selected. Er:YAG laser irradiation is thus a potential therapy for human infected root canals. PMID- 20574841 TI - Effects of radiation quality on interactions between oxidative stress, protein and DNA damage in Deinococcus radiodurans. AB - Ionizing radiation damages DNA and also induces oxidative stress, which can affect the function of proteins involved in DNA repair, thereby causing repair of DNA damage to become less efficient. We previously developed a mathematical model of this potentially synergistic relationship and applied it to gamma-ray exposure data on the radiation-resistant prokaryote Deinococcus radiodurans. Here, we investigate the effects of radiation quality on these processes by applying the model to data on exposures of D. radiodurans to heavy ions with linear energy transfer (LET) of 18.5-11,300 keV/MUm. The model adequately describes these data using three parameters combinations: radiogenic DNA damage induction, repair protein inactivation and cellular repair capacity. Although statistical uncertainties around best-fit parameter estimates are substantial, the behaviors of model parameters are consistent with current knowledge of LET effects: inactivation cross-sections for both DNA and proteins increase with increasing LET; DNA damage yield per unit of radiation dose also increases with LET; protein damage per unit dose tends to decrease with LET; DNA and especially protein damage yields are reduced when cells are irradiated in the dry state. These results suggest that synergism between oxidative stress and DNA damage may play an important role not only during gamma-ray exposure, but during high-LET radiation exposure as well. PMID- 20574842 TI - Constitutive expression of a fungal glucose oxidase gene in transgenic tobacco confers chilling tolerance through the activation of antioxidative defence system. AB - Scientific evidences in the literature have shown that plants treated exogenously with micromole concentration of hydrogen peroxide (H(2)O(2)) acquire abiotic stress tolerance potential, without substantial disturbances in the endogenous H(2)O(2) pool. In this study, we enhanced the endogenous H(2)O(2) content of tobacco (Nicotiana tabaccum L. cv. SR1) plants by the constitutive expression of a glucose oxidase (GO; EC 1.1.3.4) gene of Aspergillus niger and studied their cold tolerance level. Stable integration and expression of GO gene in the transgenic (T(0)-T(2)) tobacco lines were ascertained by molecular and biochemical tests. Production of functionally competent GO in transgenic plants was confirmed by the elevated levels of H(2)O(2) in the transformed tissues. When three homozygous transgenic lines were exposed to different chilling temperatures for 12 h, the electrolyte conductivity was significantly lower in GO-expressing tobacco plants than the control plants; in particular, chilling protection was more prominent at -1 degree C. In addition, most transgenic lines recovered within a week when returned to normal culture conditions after -1 degree C-12 h cold stress. However, control plants displayed symptoms of chilling injuries such as necrosis of shoot tip, shoots and leaves, consequently plant death. The protective effect realized in the transgenic plants was comparable to cold acclimatized wild tobacco. The chilling tolerance of transgenic lines was found associated, at least in part, with elevated levels of total antioxidant content, CAT and APX activities. Based on our findings, we predict that the transgenic expression of GO may be deployed to improve cold tolerance potential of higher plants. PMID- 20574843 TI - Associations of 9p21 variants with cutaneous malignant melanoma, nevi, and pigmentation phenotypes in melanoma-prone families with and without CDKN2A mutations. AB - Chromosome 9p21 has been implicated in the pathogenesis of cutaneous malignant melanoma (CMM). In addition to CDKN2A, the major known high-risk susceptibility gene for CMM, recent studies suggest that other 9p21 genes may be involved in melanoma/nevi development. To identify 9p21 variants that influence susceptibility to CMM and number of nevi in CMM-prone families with and without CDKN2A mutations, we analyzed 562 individuals (183 CMM) from 53 families (23 CDKN2A+, 30 CDKN2A-) for 233 tagging SNPs in 21 genes at 9p21. Single SNP- and gene-based regression analyses were used to assess the risk of CMM, nevi count, skin complexion, and tanning ability associated with these SNPs and genes. We found that SNP rs7023329 in the MTAP gene was associated with number of nevi (P (trend) = 0.003) confirming a recent finding by a genome-wide association study. In addition, three SNPs in the ACO1 gene, rs7855483 (P (trend) = 0.002), rs17288067 (P (trend) = 0.0009), and rs10813813 (P (trend) = 0.005), showed the strongest associations with CMM risk. None of the examined 9p21 SNPs was associated with skin complexion, whereas two SNPs, rs10964862 in IFNW1 (P (trend) = 0.003), and rs13290968 in TUSC1 (P (trend) = 0.0006), were associated with tanning ability. Gene-based analyses suggested that the ACO1 gene was significantly associated with CMM (P = 0.0004); genes IFNW1 (P = 0.002) and ACO1 (P = 0.0002) were significantly associated with tanning ability. Our findings are consistent with recent proposals that additional 9p21 genes may contribute to CMM susceptibility in CMM-prone families. These genetic variants may, at least partially, exert their effects through nevi and tanning ability. PMID- 20574844 TI - Depression following marital problems: different impacts on mothers and their children? A 21-year prospective study. AB - PURPOSE: With increased rates of marital breakdown it is important to identify the long-term mental health outcomes of marital problems and marital change for mothers and their children. Of particular interest is the possibility that mothers may benefit from leaving a relationship, but their children may not. This study examines the effects of marital quality and marital change on symptoms of depression in mothers and their children over 21 years. METHOD: Data (3,512 mothers and 3,334 children) were from Mater-University of Queensland Study of Pregnancy (MUSP), a population-based birth cohort study, which commenced in Brisbane, Australia, in 1981. Mothers and children were followed up at birth, 6 months and 5, 14 and 21 years after the initial interview. Marital status and marital quality were assessed at 5 and 14 years. Symptoms of depression were assessed in mothers and children at the 21-year follow-up. RESULTS: A poor quality marital relationship at the 14-year follow-up was associated with increased symptoms of depression in both mothers (+3.3 symptoms) and children (+1.1 symptoms) 7 years later. Symptoms of depression in the mother improved if she changed to unpartnered status (-1.31 symptoms); however, children experienced an increase in depression (+1.30 symptoms). There was a substantial increase in mothers' depression (+3.9 symptoms) associated with a poor reconstructed relationship but no change for children (0.68). CONCLUSION: Marital transitions may improve symptoms of depression in the mothers but not in their children. Clinical decisions for families living in some difficult marital relationships need to take into account the association between maternal and child mental health particularly evidence from clinical samples that remission of depression in the mother improves outcomes for the child. PMID- 20574845 TI - The contribution of charcoal burning to the rise and decline of suicides in Hong Kong from 1997-2007. AB - BACKGROUND: There has been scant research exploring the relationship between choice of method (means) of self-inflicted death, and broader social or contextual factors. The recent emergence and growth of suicide using carbon monoxide poisoning resulting from burning charcoal in an enclosed space (hereafter, "charcoal burning") was related to an increase in the overall suicide rate in Hong Kong. The growth of this method coincided with changing economic conditions. This paper expands upon previous work to explore possible relationships further. PURPOSE: This study aims to discern the role of charcoal burning in overall suicide rate transition during times of both economic recession and expansion, as captured in the unemployment rate of Hong Kong, and to examine whether there was evidence of an effect from means-substitution. METHODS: Age and gender specific suicide rates in Hong Kong by suicide methods from 1997 to 2007 were calculated. To model the transition of suicide rate by different methods, Poisson regression analyses were employed. RESULTS: Charcoal burning constituted 18.3% of all suicides, 88% of which involved individuals drawn from the middle years (25-59) of life. During both periods of rising and declining unemployment, charcoal burning played an important role in the changing suicide rates, and this effect was most prominent among for those in their middle years. Means-substitution was found among the married women during the period of rate advancement (1997-2003). CONCLUSIONS: Compared to others, working-age adults preferentially selected carbon monoxide poisoning from charcoal burning. PMID- 20574846 TI - Patterns of depression in cancer patients: an indirect test of gender-specific vulnerabilities to depression. AB - BACKGROUND: Higher rates of depression in women compared to men have been attributed to intrinsic biological or psychological vulnerabilities, to their disproportionate exposure to stressful events and circumstances, or to the combined contributions of these factors. PURPOSE: This study aimed to determine if there is a gender disparity in depression rates in patients with advanced cancer, a circumstance associated with multiple stressors and a high prevalence of depression. METHOD: Data were collected from 569 patients, assessing demographic characteristics, depressive symptoms, physical symptoms, and social support. RESULTS: Clinically significant symptoms of depression (BDI-II scores >=16) were reported by more than 20% of the sample, with no significant gender differences in depression. There were no significant gender differences in potentially confounding factors such as social support or physical symptom burden. CONCLUSION: The results indicated that men and women may be equally likely to develop depression when faced with a highly stressful circumstance. PMID- 20574847 TI - Complementary effect of natural and sexual selection against immigrants maintains differentiation between locally adapted fish. AB - Adaptation to ecologically heterogeneous environments can drive speciation. But what mechanisms maintain reproductive isolation among locally adapted populations? Using poeciliid fishes in a system with naturally occurring toxic hydrogen sulfide, we show that (a) fish from non-sulfidic sites (Poecilia mexicana) show high mortality (95 %) after 24 h when exposed to the toxicant, while locally adapted fish from sulfidic sites (Poecilia sulphuraria) experience low mortality (13 %) when transferred to non-sulfidic water. (b) Mate choice tests revealed that P. mexicana females exhibit a preference for conspecific males in non-sulfidic water, but not in sulfidic water, whereas P. sulphuraria females never showed a preference. Increased costs of mate choice in sulfidic, hypoxic water, and the lack of selection for reinforcement due to the low survival of P. mexicana may explain the absence of a preference in P. sulphuraria females. Taken together, our study may be the first to demonstrate independent but complementary-effects of natural and sexual selection against immigrants maintaining differentiation between locally adapted fish populations. PMID- 20574848 TI - On the structure-bounded growth processes in plant populations. AB - If growing cells in plants are considered to be composed of increments (ICs) an extended version of the law of mass action can be formulated. It evidences that growth of plants runs optimal if the reaction-entropy term (entropy times the absolute temperature) matches the contact energy of ICs. Since these energies are small, thermal molecular movements facilitate via relaxation the removal of structure disturbances. Stem diameter distributions exhibit extra fluctuations likely to be caused by permanent constraints. Since the signal-response system enables in principle perfect optimization only within finite-sized cell ensembles, plants comprising relatively large cell numbers form a network of size limited subsystems. The maximal number of these constituents depends both on genetic and environmental factors. Accounting for logistical structure-dynamics interrelations, equations can be formulated to describe the bimodal growth curves of very different plants. The reproduction of the S-bended growth curves verifies that the relaxation modes with a broad structure-controlled distribution freeze successively until finally growth is fully blocked thus bringing about "continuous solidification". PMID- 20574849 TI - Clinical utility of positron emission tomography/computed tomography in inflammatory bowel disease. AB - PURPOSE: The clinical utility of positron emission tomography/computed tomography (PET/CT) in comparison to standard workup in patients with known or suspected inflammatory bowel disease (IBD) is unknown. PROCEDURES: Clinical data were collected on seven patients with known or suspected IBD undergoing PET/CT. Standard workup included history, physical exam, laboratory tests, colonoscopy and/or cross-sectional imaging. We divided the intestine into five regions [small bowel and four colon (ascending, transverse, descending and rectosigmoid)] and graded relative standard uptake values 0, 1, 2 or 3 by comparison to the liver, using a region-of-interest analysis (0 = no activity, 1 = liver, 2 and 3 = significant inflammation). RESULTS: In patients 1 and 2, PET/CT demonstrated more activity than we thought clinically present. The other patients avoided unnecessary escalation or initiation of IBD therapy based on PET/CT results. Compared with standard workup, all seven patients had superior results when therapeutic decisions were based on PET/CT. CONCLUSIONS: We found PET/CT to be very useful in diagnosis and management in patients with known or suspected IBD. PMID- 20574850 TI - Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers. AB - Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by (1)H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents. PMID- 20574853 TI - [S3 guidelines on dementia. Symptomatic therapy of dementia]. AB - Current treatment of Alzheimer's disease comprises pharmacological therapy and psychosocial interventions for patients and caregivers in the context of a symptom and severity dependent management concept. Treatment is targeted towards the core symptoms of dementia (cognitive and functional deficits) and if necessary, towards the behavioral symptoms of dementia. The treatment of Alzheimer's dementia with acetylcholine esterase inhibitors (AChE-I; donepezil, galantamine, rivastigmine) and memantine is evidence-based and recommended. For all drugs, the highest tolerable dose should be given. The choice of AChE-I depends on the side-effects and interaction profile, as there is no convincing evidence of a relevant superiority of one of the drugs over another. Mixed dementia should be treated as Alzheimer's dementia. Treatment of vascular dementia with AChE-I or memantine is off-label and without convincing evidence. There is no convincing evidence for the treatment of frontotemporal dementia or Lewy body dementia. Rivastigmine is effective for the treatment of dementia with Parkinson's disease. PMID- 20574851 TI - Protein-based MRI contrast agents for molecular imaging of prostate cancer. AB - PURPOSE: The purpose of this study was to demonstrate a novel protein-based magnetic resonance imaging (MRI) contrast agent that has the capability of targeting prostate cancer and which provides high-sensitivity MR imaging in tumor cells and mouse models. PROCEDURE: A fragment of gastrin-releasing peptide (GRP) was fused into a protein-based MRI contrast agent (ProCA1) at different regions. MR imaging was obtained in both tumor cells (PC3 and H441) and a tumor mouse model administrated with ProCA1.GRP. RESULTS: PC3 and DU145 cells treated with ProCA1.GRPs exhibited enhanced signal in MRI. Intratumoral injection of ProCA1.GRP in a PC3 tumor model displayed enhanced MRI signal. The contrast agent was retained in the PC3 tumor up to 48 h post-injection. CONCLUSIONS: Protein based MRI contrast agent with tumor targeting modality can specifically target GRPR-positive prostate cancer. Intratumoral injection of the ProCA1 agent in the prostate cancer mouse model verified the targeting capability of ProCA1.GRP and showed a prolonged retention time in tumors. PMID- 20574854 TI - Health-related quality of life in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome. AB - OBJECTIVE: To examine the health-related quality of life (HRQoL) and factors associated with HRQoL in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using two generic preference-based HRQoL instruments, EQ 5D (plus EQ-VAS) and SF-6D, with the results compared with general population. METHOD: CP/CPPS patients were recruited from two tertiary referral hospitals, and the general populations were randomly approached. After informed consent, subjects were interviewed using EQ-5D, EQ-VAS and SF-6D, and their socio demographic and medical information was solicited. RESULTS: Compared to the general population (n = 364), CP/CPPS patients (n = 268) reported significantly worse HRQoL with median score of the EQ-5D utility index (0.73 vs. 0.85), SF-6D utility index (0.76 vs. 0.81), and EQ-VAS (70.0 vs. 85.0). Multiple linear regression analyses showed pain symptom had the strongest predictive power for HRQoL, compared to symptom duration and urinary symptom. Socio-demographic factors and comorbidities did not significantly contribute to poorer HRQoL. CONCLUSION: CP/CPPS patients experienced deteriorated HRQoL with lower health related utility scores compared to general population, and pain severity was the main physical symptom predicting decreased health-related utility. Further studies are needed to provide the reference utility index for the comparison and better characterizing the influence of geographic and cultural factors on variation of health-related utility of CP/CPPS patients. PMID- 20574855 TI - The effectiveness of adjustable gastric banding: a retrospective 6-year U.S. follow-up study. AB - BACKGROUND: This study aimed to assess the efficacy of laparoscopic adjustable gastric banding (LAGB) during a 6-year follow-up period. METHODS: A retrospective database analysis of patients who underwent LAGB at New York University Medical Center between 1 January 2000 and 29 February 2008 was conducted. Patients were included for the efficacy analysis if they were 18 years old or older at the surgery date and had one or more visits with a recorded weight after surgery. Efficacy was assessed using percentage of excess weight loss (%EWL) at 1-year intervals after surgery. Missing weight values were interpolated using a cubic spline function. Linear regression models were used to assess the characteristics that affected the last available %EWL. All patients had implantation of the LAP BAND system. RESULTS: The inclusion criteria for the efficacy analysis were met by 2,909 patients. The majority of the patients were white (83.3%) and female (68.4%). The mean patient age was 44.6 years, and the mean baseline body mass index (BMI) was 45.3 kg/m2. The %EWL 3 years after surgery was 52.9%, which was sustained thereafter. In multivariate models, increased number of office visits, younger age, female gender, and Caucasian race were significantly associated with a higher maximum %EWL. CONCLUSIONS: The LAP-BAND patients achieved a substantial and sustainable weight loss of approximately 50% at 6 years after surgery. PMID- 20574856 TI - European consensus on a competency-based virtual reality training program for basic endoscopic surgical psychomotor skills. AB - BACKGROUND: Virtual reality (VR) simulators have been demonstrated to improve basic psychomotor skills in endoscopic surgery. The exercise configuration settings used for validation in studies published so far are default settings or are based on the personal choice of the tutors. The purpose of this study was to establish consensus on exercise configurations and on a validated training program for a virtual reality simulator, based on the experience of international experts to set criterion levels to construct a proficiency-based training program. METHODS: A consensus meeting was held with eight European teams, all extensively experienced in using the VR simulator. Construct validity of the training program was tested by 20 experts and 60 novices. The data were analyzed by using the t test for equality of means. RESULTS: Consensus was achieved on training designs, exercise configuration, and examination. Almost all exercises (7/8) showed construct validity. In total, 50 of 94 parameters (53%) showed significant difference. CONCLUSIONS: A European, multicenter, validated, training program was constructed according to the general consensus of a large international team with extended experience in virtual reality simulation. Therefore, a proficiency-based training program can be offered to training centers that use this simulator for training in basic psychomotor skills in endoscopic surgery. PMID- 20574857 TI - Video. Chopstick surgery: a novel technique enables use of the Da Vinci Robot to perform single-incision laparoscopic surgery. AB - INTRODUCTION: Single-incision laparoscopic surgery (SILS) is limited by the coaxial arrangement of the instruments. A surgical robot with "wristed" instruments could overcome this limitation but the "arms" collide when working coaxially. This video demonstrates a new technique of "chopstick surgery," which enables use of the robotic arms through a single incision without collision. METHODS: Experiments were conducted utilizing the da Vinci S(r) robot (Sunnyvale, CA) in a porcine model with three laparoscopic ports (12 mm, 2-5 mm) introduced through a single "incision." Pilot work conducted while performing Fundamentals of Laparoscopic Surgery (FLS) tasks determined the optimal setup for SILS to be a triangular port arrangement with 2-cm trocar distance and remote center at the abdominal wall. Using this setup, an experienced robotic surgeon performed a cholecystectomy and nephrectomy in a porcine model utilizing the "chopstick" technique. The chopstick arrangement crosses the instruments at the abdominal wall so that the right instrument is on the left side of the target and the left instrument on the right. This arrangement prevents collision of the external robotic arms. To correct for the change in handedness, the robotic console is instructed to drive the "left" instrument with the right hand effector and the "right" instrument with the left. RESULTS: Both procedures were satisfactorily completed with no external collision of the robotic arms, in acceptable times and with no technical complications. This is consistent with results obtained in the box trainer where the chopstick configuration enabled significantly improved times in all tasks and decreased number of errors and eliminated instrument collisions. CONCLUSION: Chopstick surgery significantly enhances the functionality of the surgical robot when working through a small single incision. This technique will enable surgeons to utilize the robot for SILS and possibly for intraluminal or transluminal surgery. PMID- 20574859 TI - Editorial: Fuchs' uveitis: from Imperial Vienna to global appraisal. PMID- 20574858 TI - EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992. AB - Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer and is associated with significant mortality and morbidity worldwide. Despite improvements in conventional treatment for NSCLC, survival remains poor and improvements in patient outcome are warranted. Over recent years, basic scientific research has dramatically increased our knowledge of the pathogenesis of lung cancer and allowed us to uncover and understand the cellular pathways involved in this process. This has led to the development of therapies to selectively target these pathways. Among these, the epidermal growth factor receptor (EGFR) tyrosine kinase family and related downstream pathways play a critical role in cancer development and over recent years have become a validated target in NSCLC. The development of monoclonal antibodies and first-generation tyrosine kinase inhibitors (TKIs) targeted towards EGFR has had a considerable impact on patient outcomes. However, despite dramatic and sustained responses and the discovery of specific patient subgroups that may derive clinical benefit, resistance to first-generation EGFR TKIs inevitably develops. A new generation of agents have been developed to provide superior potency of target inhibition and further individualize the treatment of NSCLC. This article reviews EGFR-targeted therapies currently available for use and undergoing clinical development for the treatment of NSCLC, specifically focusing on next generation agents including BIBW 2992, an irreversible dual inhibitor of EGFR and HER2 kinases. PMID- 20574861 TI - A green version of Haeckel's rule. PMID- 20574862 TI - Spatial working memory in aging and mild cognitive impairment: effects of task load and contextual cueing. AB - Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression. PMID- 20574860 TI - Hijacking the endocytic machinery by microbial pathogens. AB - Understanding the mechanisms that microbes exploit to invade host cells and cause disease is crucial if we are to eliminate their threat. Although pathogens use a variety of microbial factors to trigger entry into non-phagocytic cells, their targeting of the host cell process of endocytosis has emerged as a common theme. To accomplish this, microbes often rewire the normal course of particle internalization, frequently usurping theoretical maximal sizes to permit entry and reconfiguring molecular components that were once thought to be required for vesicle formation. Here, we discuss recent advances in our understanding of how toxins, viruses, bacteria, and fungi manipulate the host cell endocytic machinery to generate diseases. Additionally, we will reveal the advantages of using these organisms to expand our general knowledge of endocytic mechanisms in eukaryotic cells. PMID- 20574863 TI - Self-reported non-adherence to ART and virological outcome in a multiclinic UK study. AB - Adherence is of fundamental importance to ART success. We examined the association of self-reported non-adherence with demographic factors, health and behaviour issues, and virological outcome, in a multi-clinic study. Seven hundred and seventy-eight HIV patients in five clinics in London and Brighton completed a questionnaire on adherence and HIV/health issues at baseline in 2005/6. For 486 subjects taking ART, non-adherence in the past week was defined as: (A)>or=1 dose missed or taken incorrectly (wrong time/circumstances); (B)>or=1 dose missed; (C)>or=2 doses missed. Questionnaire data were matched with routine treatment and virology data for consenting subjects (61.4%). We assessed four virological outcomes in 307 of 486 patients: (i) VL>50c/mL using latest VL at the questionnaire and excluding patients starting HAART<24 weeks ago; (ii) VL>50c/mL using the first VL from 6 to 12 months post-questionnaire; (iii) any VL>50c/mL from 6 to 12 months post-questionnaire; (iv) among patients with VL<50c/mL at questionnaire, time to first subsequent VL>50c/mL over two years follow up. Non adherence was reported by 278 (57.2%), 102 (21.0%) and 49 (10.1%) of 486 patients, for definitions A, B and C, respectively. Non-adherence declined markedly with older age, and tended to be more commonly reported by Black patients, those born outside the UK, those with greater psychological symptoms and those with suicidal thoughts. There was a weaker association with physical symptoms and no association with gender/sexuality, education, unemployment, or risk behaviour (p>0.1). In logistic regression analyses, younger age, non-UK birth and psychological variables were independent predictors of non-adherence [e.g., for non-adherence B: odds ratios (95% CI) were 0.95 (0.92, 0.98) for every year older age; 1.6 (1.0, 2.5) for non-UK born; 2.3 (1.5, 3.7) for suicidal thoughts]. Non-adherence was associated with poorer virological outcome; the most consistent association was for definition C. Among 255 patients with VL<50c/mL at baseline, non-adherence definition C was independently associated with subsequent VL>50c/mL [adjusted hazard ratio (95% CI) 3.2 (1.5, 7.2)]. Non-UK birth and psychological symptoms predicted non-adherence, but the most striking association was with younger age. Age should be an important consideration in clinical strategies to minimise non-adherence and in decisions regarding ART initiation. A simple measure of non-adherence can identify patients at risk of poorer virological outcome. PMID- 20574864 TI - The nature of the automatization deficit in Chinese children with dyslexia. AB - Clarifying whether automatization deficits constitute the primary causes or symptoms of developmental dyslexia, we focused on three critical issues of the dyslexic automatization deficit, namely universality, domain specificity, and severity. Thirty Chinese dyslexic children (mean age 10 years and 5 months), 30 chronological-age-, and 30 reading-level-matched children were tested in 4 areas of automaticity: motor, visual search, Stroop facilitation effects, and automatic word recognition. The results showed that the dyslexic children performed significantly worse than the CA-controls but not the RL-controls in all the tasks except for Stroop congruent-color words, on which they performed worse than children in both control groups. The deficits reflect a lag in reading experiences rather than a persistent cognitive deficit. PMID- 20574865 TI - Attention, response inhibition, and face-information processing in children: the role of task characteristics, age, and gender. AB - The aim of the study was to assess: (a) developmental changes in attention, response inhibition, and face-information processing using the new Balloons task and (b) to evaluate the association between measures derived from the task with reported behavior problems. One hundred and thirty-four typically developing children (53 boys and 81 girls) were tested with the Balloons. Their parents and teachers completed the Child Behavior Checklist. Our results validate the Balloons as a reliable task with significant effects of manipulations in difficulty level (speed, processing load, and processing type). The results suggest that face-information processing undergoes significant changes during the age period between 7 and 13 years with significant gender differences. Modest but significant correlations were found between the Balloons' measures and behavior problems. PMID- 20574866 TI - DSM-IV-defined inattention and sluggish cognitive tempo: independent and interactive relations to neuropsychological factors and comorbidity. AB - The aim of the present study was to investigate the independent relations of DSM IV-defined inattention and behaviors characteristic of sluggish cognitive tempo (SCT) to neuropsychological factors and problem behaviors often comorbid with attention deficit/hyperactivity disorder (ADHD). By controlling for symptoms of DSM-IV-defined inattention, unique relations to SCT could be ascertained. Additionally, interactive relations of DSM-IV-defined inattention and SCT were of interest. A community-based sample of school children (N = 209; the higher end of the ADHD-symptom range was oversampled) completed neuropsychological tasks designed to measure executive function (EF), sustained attention, and state regulation. Behavioral symptoms were measured using parental and teacher ratings of the DSM-IV criteria for ADHD and Oppositional Defiant Disorder (ODD). The results showed that these two domains of inattention, DSM-IV-defined inattention and SCT, have neuropsychological processes and comorbid behavioral problems in common. However, when controlling for the overlap, DSM-IV-defined inattention was uniquely related to EF and state regulation, while SCT was uniquely related to sustained attention. In addition, the results showed an interactive relation of DSM-IV-defined inattention and SCT to ODD. Findings from the present study support the notion that DSM-IV-defined inattention constitutes a somewhat heterogeneous condition. Such results can further our theoretical understanding of the neuropsychological impairments and comorbid behavioral problems associated with ADHD symptoms. PMID- 20574867 TI - Visual perception and memory impairments in children at risk of nonverbal learning disabilities. AB - Visuospatial working memory (VSWM) and visual perception were examined in two groups aged 11-13, one with children displaying symptoms of nonverbal learning disability (NLD) (n = 18) and the other a control group without learning disabilities (n = 18). The two groups were matched for general verbal abilities, age, gender, and socioeconomic level. The children were presented with VSWM tests involving visual and spatial-simultaneous processes, and also with a classical visual illusion, a classical ambiguous figure, as well as visual perception tests specifically devised for the present study. Results revealed that performance of children at risk of NLD was worse than controls in some VSWM and in visual perception tests without memory involvement; these latter required comparisons of visual stimuli and locations in space with distractors. Moreover, the two groups differed in perceiving the classical ambiguous figure. Findings are discussed in the light of both theoretical and clinical implications. PMID- 20574868 TI - Behavior of zinc, nickel, copper and cadmium during the electrokinetic remediation of sediment from the Great Backa Canal (Serbia). AB - This paper describes a bench-scale study dealing with the removal of heavy metals by electrokinetic (EK) remediation from sediment of the Great Backa Canal (Vojvodina, Republic of Serbia), with an emphasis on the dependence of removal efficacies on the physicochemical states of the heavy metals and sediment chemistry. Sediment samples were spiked with the following heavy metals (mg kg( 1)): Zn 4400, Ni 900, Cu 1140 and Cd 57. In addition to determining the pseudo total metal content in the contaminated sediment before and after EK treatment, BCR sequential extraction was also performed to examine the distribution of the contaminants in the sediment. Conventional EK remediation (EXP I) was ineffective in removing the heavy metals investigated, so two enhanced processes were developed. In both these processes, the mass of treated sediment was reduced to avoid the presence of inactive electric field areas in the sediment and increase current density. The first enhanced experiment (EXP II) used acetic acid (HAc) solution (pH 2.9) as an anolyte. Combined with the smaller sediment mass, this resulted in an increase in overall removal efficacies (9% for Zn, 15% for Ni, 10% for Cu and 15% for Cd). The second enhanced experiment (EXP III), as well as using HAc solution as an anolyte, made use of a cation exchange membrane in the cathodic chamber to minimize pH changes in the region adjacent to the cathode, which negatively influenced the removal of some heavy metals. However, no improvement in removal efficacy was achieved in EXP III. Since the redox potential of the sediment drops during the EK process, metals removal is limited by the formation of their sulfides. In conclusion, the removal of heavy metals by EK remediation is governed by a complex interplay of the complexation, precipitation and reduction processes, and the difficulties encountered in their optimization can explain the unsatisfactory effectiveness achieved by the described remediation procedure. Improved understanding of the behavior of metal ions during EK treatment can be useful in predicting and enhancing the efficacy of the process. PMID- 20574869 TI - Minor crops for export: a case study of boscalid, pyraclostrobin, lufenuron and lambda-cyhalothrin residue levels on green beans and spring onions in Egypt. AB - Dissipation rates of boscalid [2-chloro-N-(4' -chlorobiphenyl-2-yl)nicotinamide], pyraclostrobin [methyl 2-[1-(4-chlorophenyl) pyrazol-3-yloxymethyl]-N methoxycarbanilate], lufenuron [(RS)-1-[2,5-dichloro-4-(1,1,2,3,3,3 hexafluoropropoxy)phenyl]-3-(2,6-difluorobenzoyl)urea] and lambda-cyhalothrin [(R)-cyano(3-phenoxyphenyl)methyl (1S,3S)-rel-3-[(1Z)-2-chloro-3,3,3-trifluoro-1 propenyl]-2,2-dimethylcyclopropanecarboxylate] in green beans and spring onions under Egyptian field conditions were studied. Field trials were carried out in 2008 in a Blue Nile farm, located at 70 kilometer (km) from Cairo (Egypt). The pesticides were sprayed at the recommended rate and samples were collected at pre determined intervals. After treatment (T(0)) the pesticide residues in green beans were 7 times lower than in spring onions. This is due to a different structure of vegetable plant in the two crops. In spring onions, half-life (t(1/2)) of pyraclostrobin and lufenuron was 3.1 days and 9.8 days respectively. At day 14th (T(14)) after treatment boscalid residues were below the Maximum Residue Limit (MRL) (0.34 versus 0.5 mg/kg), pyraclostrobin and lambda cyhalothrin residues were not detectable (ND), while lufenuron residues were above the MRL (0.06 versus 0.02 mg/kg). In green beans, at T(0), levels of boscalid, lufenuron and lambda -cyhalothrin were below the MRL (0.28 versus 2 mg/kg; ND versus 0.02 mg/kg; 0.06 versus 0.2 mg/kg, respectively) while, after 7 days treatment (T(7)) pyraclostrobin residues were above the MRL (0.03 versus 0.02 mg/kg). However, after 14 days the residue level could go below the MRL (0.02 mg/kg), as observed in spring onions. PMID- 20574870 TI - Biodegradation of chlorimuron-ethyl by the bacterium Klebsiella jilinsis 2N3. AB - Enrichment culturing of sludge taken from an industrial wastewater treatment pond led to the identification of a bacterium (Klebsiella jilinsis H. Zhang) that degrades chlorimuron-ethyl with high efficiency. Klebsiella jilinsis strain 2N3 grows with chlorimuron-ethyl as the sole nitrogen source at the optimal temperature range of 30-35 degrees C and pH values between 6.0-7.0. In liquid medium, the degradation activity was further induced by chlorimuron-ethyl. Degradation rates followed the pesticide degradation kinetic equation at concentrations between 20 and 200 mg L(-1). Using initial concentrations of 20 and 100 mg L(-1), the degradation rates of chlorimuron-ethyl were 83.5 % and 92.5 % in 12 hours, respectively. At an initial concentration higher than 200 mg L( 1), the degradation rate decreased slightly as the concentration increased. The 2N3 strain also degraded the sulfonylurea herbicides ethametsulfuron, metsulfuron methyl, nicosulfuron, rimsulfuron, and tribenuron-methyl. This study provides scientific evidence and support for the application of K. jilinsis in bioremediation to reduce environmental pollution. PMID- 20574871 TI - A rapid and sensitive fluoroimmunoassay based on quantum dot for the detection of chlorpyrifos residue in drinking water. AB - A rapid and sensitive indirect competitive fluorescence-linked immunosorbent assay (cFLISA) method based on quantum dots as the fluorescence label coupled with secondary antibody (Ab(2)) for the detection of chlorpyrifos in drinking water has been developed. The cFLISA method allowed for chlorpyrifos determination in a liner working range of 15.2-205.5 ng mL(-1). The 50 % inhibition value (IC(50)) and the limit of detection (LOD) of the cFLISA were 50.2 ng mL(-1) and 8.4 ng mL(-1), while the IC(50) and the LOD of the conventional enzyme linked immunosorbent assay (ELISA) were 95.3 ng- mL(-1) and 16.2 ng mL(-1), respectively. When the concentrations of chlorpyrifos were 200, 100 and 50 ng mL(-1), the recoveries ranged from 90.8 % to 108.2 % with a coefficient of variation (CV) of 7.5 %-15.2 %. In water sample analysis, the results of cFLISA were similar to those obtained from a cELISA and a high performance liquid chromatography (HPLC) method, while the detection time by cFLISA was reduced 0.5 h compared with ELISA. It showed that cFLISA could be used as a new screening method for the detection of pesticide residue. PMID- 20574872 TI - Application of a permethrin immunosorbent assay method to residential soil and dust samples. AB - A low-cost, high throughput bioanalytical screening method was developed for monitoring cis/trans-permethrin in dust and soil samples. The method consisted of a simple sample preparation procedure [sonication with dichloromethane followed by a solvent exchange into methanol:water (1:1)] with bioanalytical detection using a magnetic particle enzyme-linked immunosorbent assay (ELISA). Quantitative recoveries (83-126%) of cis/trans-permethrin were obtained for spiked soil and dust samples. The percent difference of duplicate ELISA analyses was within +/- 20% for standards and +/- 35% for samples. Similar sample preparation procedures were used for the conventional gas chromatography/mass spectrometry (GC/MS) analysis except that additional cleanup steps were required. Recoveries of cis/trans-permethrin ranged from 81 to 108% for spiked soil and dust samples by GC/MS. The ELISA-derived permethrin concentrations were highly correlated with the GC/MS-derived sum of cis/trans-permethrin concentrations with a correlation coefficient (r) of 0.986. The ELISA method provided a rapid qualitative screen for cis/trans-permethrin in soil and dust while providing a higher sample throughput with a lower cost as compared to the GC/MS method. The ELISA can be applied as a complementary, low-cost screening tool to prioritize and rank samples prior to instrumental analysis for exposure studies. PMID- 20574873 TI - Microwave synthesis and antifungal evaluations of some chalcones and their derived diaryl-cyclohexenones. AB - Microwave irradiation (MWI) of acetophenones and substituted benzaldehydes in water resulted in a "green-chemistry" procedure for the preparation of chalcones (1-14), through base catalyzed Claisen-Schmidt condensation reaction, in good yields. Further 3,5-diaryl-6-carbethoxy-2-cyclohexen-1-ones (1a-14a) were prepared through base catalyzed cyclocondensation of above chalcones with ethylacetoacetate using MWI as the energy source and silica as support. Out of fourteen cyclohexenones, ten (1a, 4a, 5a, 6a, 7a, 9a, 10a, 11a, 12a and 13a) are reported for the first time in literature. The synthesized compounds were characterized using various spectroscopic techniques, viz. ((1)H NMR and IR) and screened for their antifungal activity in vitro against Sclerotium rolfsii and Rhizoctonia solani by poisoned food technique. The compounds tested were found to be active against R. solani whereas against S. rolfsii, moderate activity was observed, as evident from LC(50) values. The most potent compounds against R. solani were 1-(4-Fluoro-phenyl)-3-phenyl-propenone (13) and 1,3-Diphenyl propenone (14) having LC(50) values of 2.36 and 2.49 mg L(- 1) respectively (LC(50) of Hexaconazole = 1.12 mg L(- 1)) and against S. rolfsii 3-(4-Fluoro phenyl)-5-(3-nitro-phenyl)-6-carbethoxy-2-cyclohexen-1-one (12a) was most active having LC(50) value of 285 mg L(- 1)compared to Hexaconazole (LC(50) = 1.27 mg L( 1)). PMID- 20574874 TI - A call to action: the global effort on women's and children's health. PMID- 20574875 TI - Sports celebrities and public health: Diego Maradona's influence on drug use prevention. AB - Exposure to a sports celebrity through media and sporting events can have important influences on a public health issue associated with that celebrity. The battle against drug use by Argentinean soccer icon Diego Maradona has provoked concerns about drug abuse and prevention in Argentina, particularly among young people. The present study analyzes how two forms of involvement with Maradona affected the public's concern and perceptions of drug use after Maradona's drug related health crisis in 2004. Results indicate that those who had a greater degree of parasocial interaction with Maradona were more likely to have an increased awareness of drug abuse, a greater personal concern about drug abuse, abstained from drug use, and more strongly support drug abuse prevention programs. In contrast, identification with Maradona had a mitigating effect on drug use prevention. Implications of these findings regarding the influence of sports celebrities on substance abuse are discussed. PMID- 20574876 TI - A mass mediated intervention on Hispanic live kidney donation. AB - This research examines the impact of a Spanish language mass media campaign on living organ donation attitudes and behavioral intentions among Spanish dominant Hispanics in Tucson, Arizona. Impact was assessed via a pretest/posttest control group quasiexperimental design with Tucson, Arizona, as the intervention community and Phoenix, Arizona, as the control. Preintervention focus groups provided qualitative data to guide intervention development, while telephone surveys in both communities provided quantitative data to assess campaign impact. Analyses reveal pretest/posttest differences in the intervention community such that posttest intentions regarding living organ donation behaviors increased from pretest. No such differences were observed in the control community. Subsequent analyses revealed differences between respondents in the intervention community exposed to the campaign vs. those in the same community not exposed to the campaign. Exposed respondents reported more positive living organ donation behavioral intentions than nonexposed respondents. Implications for research and practice are discussed. PMID- 20574877 TI - HIV/AIDS stigma and religiosity among African American women. AB - African American women are disproportionately affected by HIV/AIDS compared with other ethnicities, accounting for two-thirds (67%) of all women diagnosed with HIV. Despite their increased risk of HIV infection, few studies have been conducted to understand culture-specific factors leading to their vulnerability. Given the central role of religious organizations in African American communities, this study explored whether and to what extent religiosity plays a role in stigma toward HIV/AIDS. Results of hierarchical regression showed that after controlling for key factors, religiosity was a significant factor predicting the level of religious stigma. Those with high religiosity displayed significantly higher stigma, associating HIV/AIDS with a curse or punishment from God. Verbatim responses to an open-ended question also revealed seemingly ingrained prejudice against HIV/AIDS from a religious perspective. The findings point to the important role of faith-based organizations (FBOs) in addressing HIV/AIDS issues within African American communities. PMID- 20574878 TI - Patients' perceptions of screening for health literacy: reactions to the newest vital sign. AB - Difficulties in caring for patients with limited health literacy have prompted interest in health literacy screening. Several prior studies, however, have suggested that health literacy testing can lead to feelings of shame and stigmatization. In this study, we examine patient reaction to the Newest Vital Sign (NVS), a screening instrument developed specifically for use in primary care. Data were collected in 2008 in the Morehouse School of Medicine, Department of Family Medicine Primary Care Clinics, where health literacy screening was implemented as part of routine intake procedures. Following the visit, patients completed a series of questions assessing their screening experiences. A total of 179 patients completed both the NVS and the reaction survey. Nearly all (> 99%) patients reported that the screening did not cause them to feel shameful. There were also no differences in the reported prevalence of shame (p 14 msec). The type I intraplaque hemorrhage size estimated by 3D SHINE was significantly and positively correlated with the size estimated manually by an expert reviewer using the histology-validated multicontrast MRI technique (r = 0.836 +/- 0.080, p < 0.001). With only one fast sequence, 3D SHINE can detect and characterize intraplaque hemorrhage that has previously required a multicontrast approach using a combination of black-blood T(1)-weighted, black-blood T(2) weighted, and time-of-flight imaging techniques. PMID- 20574967 TI - Imaging three-dimensional myocardial mechanics using navigator-gated volumetric spiral cine DENSE MRI. AB - A navigator-gated 3D spiral cine displacement encoding with stimulated echoes (DENSE) pulse sequence for imaging 3D myocardial mechanics was developed. In addition, previously described 2D postprocessing algorithms including phase unwrapping, tissue tracking, and strain tensor calculation for the left ventricle (LV) were extended to 3D. These 3D methods were evaluated in five healthy volunteers, using 2D cine DENSE and historical 3D myocardial tagging as reference standards. With an average scan time of 20.5 +/- 5.7 min, 3D data sets with a matrix size of 128 * 128 * 22, voxel size of 2.8 * 2.8 * 5.0 mm(3), and temporal resolution of 32 msec were obtained with displacement encoding in three orthogonal directions. Mean values for end-systolic mid-ventricular mid-wall radial, circumferential, and longitudinal strain were 0.33 +/- 0.10, -0.17 +/- 0.02, and -0.16 +/- 0.02, respectively. Transmural strain gradients were detected in the radial and circumferential directions, reflecting high spatial resolution. Good agreement by linear correlation and Bland-Altman analysis was achieved when comparing normal strains measured by 2D and 3D cine DENSE. Also, the 3D strains, twist, and torsion results obtained by 3D cine DENSE were in good agreement with historical values measured by 3D myocardial tagging. PMID- 20574969 TI - Conformational dynamics of active site loop in Escherichia coli phytase. AB - Phytases catalyze the release of phosphate by stepwise hydrolysis of phytate, a major source of phosphate in cereal grains, legumes, and oilseeds. Phytase improves, as a feed supplement, the nutritional quality of phytate rich diets and eventually reduce environmental pollution. Recently, phytases from enterobacteriaceae family have attracted industrial interest due to their high specific activity (2500-4000 U/mg). However, only limited information is available concerning structural dynamics of this class of enzymes. In this study, 50 nanosecond molecular dynamics simulation was performed on two Escherichia coli phytase structures (closed and open active site loop) to investigate conformational dynamics of the active site loop. Cluster analysis and principal component analysis (PCA) reveal significant difference in the conformational dynamics of active site compared to reported crystal structure. Molecular dynamic studies indicated that the movement in the active site of E. coli phytase is mainly confined by the active site loop resulted in wider opening of the loop in absence of phytate. The molecular dynamics studies highlight the possible role of loop residues as prerequisite for highly active phytases. PMID- 20574970 TI - Impact of fluorescent probes on albumin sorption profiles to ophthalmic biomaterials. AB - Bovine serum albumin (BSA) was conjugated to three organic fluorescent probes, 5 (4,6-dichloro-s-triazin-2-ylamino)fluorescein hydrochloride (DTAF), Rhodamine B isothiocyanate (RITC), and Lucifer yellow VS (LY). The protein sorption profile to one pHEMA-based (etafilcon A) and three silicone hydrogel (SH) contact lens types (lotrafilcon B, balafilcon A and senofilcon A) was determined using confocal laser scanning microscopy. In addition, all lenses were incubated in dye solutions containing the fluorescent probe alone; and in a separate experiment BSA accumulation was quantified using radiolabeling. The different fluorescent conjugates showed similar sorption profiles for the pHEMA-based lens, but marked differences for all SH lenses. Lotrafilcon B accumulated more protein on the surface as compared to the matrix, independent of the fluorescent probe used for conjugation. Protein sorption varied for senofilcon A, with DTAF-BSA sorbing primarily to the surface region, while the other conjugates penetrated in equal amounts into the matrix. Balafilcon A exhibited smaller differences between conjugates, with LY-BSA allowing the protein to fully penetrate the matrix, while the other conjugates showed minor surface adsorption. Sorption curves of unbound dyes were often similar compared to the conjugated results. BSA profiles to pHEMA based and silicone hydrogel lenses were highly dependent on the fluorescent probe used and none of the probes accurately reflected quantitative protein levels for the lens materials investigated. PMID- 20574971 TI - Evaluation of human osteoblastic cell response to plasma-sprayed silicon substituted hydroxyapatite coatings over titanium substrates. AB - Silicon-substituted hydroxyapatite (Si-HA) coatings have been plasma sprayed over titanium substrates (Ti-6Al-4V) aiming to improve the bioactivity of the constructs for bone tissue repair/regeneration. X-ray diffraction analysis of the coatings has shown that, previous to the thermal deposition, no secondary phases were formed due to the incorporation of 0.8 wt % Si into HA crystal lattice. Partial decomposition of hydroxyapatite, which lead to the formation of the more soluble phases of alpha- and beta-tricalcium phosphate and calcium oxide, and increase of amorphization level only occurred following plasma spraying. Human bone marrow-derived osteoblastic cells were used to assess the in vitro biocompatibility of the constructs. Cells attached and grew well on the Si-HA coatings, putting in evidence an increased metabolic activity and alkaline phosphatase expression comparing to control, i.e., titanium substrates plasma sprayed with hydroxyapatite. Further, a trend for increased differentiation was also verified by the upregulation of osteogenesis-related genes, as well as by the augmented deposition of globular mineral deposits within established cell layers. Based on the present findings, plasma spraying of Si-HA coatings over titanium substrates demonstrates improved biological properties regarding cell proliferation and differentiation, comparing to HA coatings. This suggests that incorporation of Si into the HA lattice could enhance the biological behavior of the plasma-sprayed coating. PMID- 20574973 TI - Histomorphology of thrombus organization, neointima formation, and foreign body response in retrieved human aneurysms treated with hydrocoil devices. AB - Biological processes, such as thrombus organization, endothelialization, and foreign body response, that occur following embolization of intracranial aneurysms are poorly understood. We examined 13 human aneurysms (retrieved at autopsy 1-74 days postembolization) treated with hybrid hydrogel-platinum coil devices and platinum coils. The specimens were embedded in methyl methacrylate and ground sections were surface stained. Using light microscopy, thrombus organization in the sac, endothelialization of the neck, and foreign body response to the embolic devices were determined. The area percentages of the sac occupied by embolic devices and unorganized thrombus were quantified using image analysis. Thrombus organization increased over time, but was incomplete up to 74 days post-treatment. Neointima formation had started at 5 days upon dense fibrin depositions and progressed to form a new vessel wall at 74 days. The foreign body response to the hydrogel was characterized by mononuclear macrophages, while platinum coils were surrounded by multinuclear foreign body giant cells. Histometric aneurysm occlusion ranged from 89 to 100% and embolic devices occupied 31-64% of the aneurysm sac. These findings showed that the hydrogel based devices occupied a large percentage of the aneurysm sac, provided a framework for thrombus organization to occur, and elicited less severe foreign body response than platinum coils. PMID- 20574972 TI - Improved biocompatibility of hydroxyapatite thin film prepared by aerosol deposition. AB - Technical development for an efficient coating of bioactive materials improves the characteristics of a fully functional implant. The aim of this study was to investigate the osteoinductive effect of a newly developed hydroxyapatite (HA) coating technique using aerosol deposition without post-heat treatment [room temperature (RT) group] on the titanium (Ti) dental implant in vitro and in vivo, compared with that of HA coating with post-heat treatment (HT-400 group) or machined surface (control group). Cell proliferation or attachment on the HA coated Ti surface was assessed using tetrazolium salt, WST-8 or scanning electron microscopy (SEM). Human osteoblasts (HOB) on RT group were well attached and grew alike in the control or HT-400 group. The alkaline phosphatase activity of HOB cultured on RT and HT-400 group was significantly higher than the control group (p < 0.05). Evaluation by SEM, TEM, and XRD demonstrated that aerosol deposition facilitated HA particles to form a dense and uniform HA layer in the RT group despite no post-heating. In a rabbit tibia model (n = 3), the ratios of bone implant contact and bone area in the RT group (49.88%, 86.05%) were greater than in the HT-400 group (38.82%, 77.34%) or the control (28.31%, 73.86%). The finding of this study showed that the HA coating using aerosol deposition without post heat treatment has a good biocompatibility, and provide a promoting strategy to enhance osseointegration in the application of the dental implant. PMID- 20574974 TI - Tungsten-rhenium suture needles with improved properties for coronary artery bypass graft surgery. AB - Suture needles are essential instruments for performing blood vessel anastomosis in coronary artery bypass graft (CABG) surgeries. Exceptional needle performance is needed now as never before because of the increasing prevalence of elderly patients with advanced stages of coronary disease and calcified tissue. The various properties that affect the performance of suture needles used in CABG surgery are reviewed and recent progress towards improving needle performance through the use of tungsten-rhenium alloys and novel lubricous needle coatings is presented. Substantial enhancement of properties beyond those exhibited by commercially available stainless steel suture needles has been made, including an approximate 40% increase in strength, 100% increase in stiffness, and superior multiple pass penetration performance in both synthetic rubber media and human cadaver carotid arteries (p < 0.01). PMID- 20574975 TI - Composite nanofiber mats consisting of hydroxyapatite and titania for biomedical applications. AB - Composite nanofiber mats (HA/TiO2) consisting of hydroxyapatite (HA) and titania (TiO2) were fabricated via an electrospinning technique and then collagen (type I) was immobilized on the surface of the HA/TiO2 composite nanofiber mat to improve tissue compatibility. The structure and morphology of the collagen immobilized composite nanofiber mat (HA/TiO2-col) was investigated using an X-ray diffractometer, electron spectroscopy for chemical analysis, and scanning electron microscope. The potential of the HA/TiO2-col composite nanofiber mat for use as a bone scaffold was assessed by an experiment with osteoblastic cells (MC3T3-E1) in terms of cell adhesion, proliferation, and differentiation. The results showed that the HA/TiO2-col composite nanofiber mats possess better cell adhesion and significantly higher proliferation and differentiation than untreated HA/TiO2 composite nanofiber mats. This result suggests that the HA/TiO2 col composite nanofiber mat has a high-potential for use in the field of bone regeneration and tissue engineering. PMID- 20574976 TI - Preparation, microstructures, mechanical properties, and cytocompatibility of TiMn alloys for biomedical applications. AB - The titanium-manganese (TiMn) alloys have been extensively used in aerospace and hydrogen storage. In this study, the TiMn alloys with various manganese contents ranging from 2 to 12 wt % were prepared by using mechanical alloying and spark plasma sintering (SPS) techniques. The microstructures, mechanical properties including hardness, elastic modulus and ductility, cytotoxicity and cell proliferation properties of the TiMn alloys were investigated to explore their biomedical applications. The addition of manganese to the titanium reduced the alpha to beta transformation temperature and was confirmed as a beta stabilizer element. The manganese increased the relative density of the alloy and thus high density TiMn alloys with alpha+beta structure were prepared by using SPS at 700 degrees C. The hardness increased significantly ranging from 2.4 GPa (Ti2Mn) to 5.28 GPa (Ti12Mn) and the elastic modulus ranging from 83.3 GPa (Ti2Mn) to 122 GPa (Ti12Mn), the ductility decreased ranging from 21.3% (Ti2Mn) to 11.7% (Ti12Mn) with increasing manganese content in the Ti. Concentrations of Mn below 8 wt % in titanium reveal negligible effects on the metabolic activity and the cell proliferation of human osteoblasts. The Mn could be used in lower concentrations as an alloying element for biomedical titanium. The Ti2Mn, Ti5Mn, and Ti8Mn alloys with supervisor mechanical properties and acceptable cytocompatibility have a potential for use as bone substitutes and dental implants. PMID- 20574977 TI - In vitro performance assessment of new brushite-forming Zn- and ZnSr-substituted beta-TCP bone cements. AB - The present study investigated the in vitro performance of brushite-forming Zn- and ZnSr-substituted beta-TCP bone cements in terms of wet mechanical strength and biological response. Quantitative phase analysis and structural refinement of the powdered samples were performed by X-ray powder diffraction and Rietveld refinement technique. Initial and final setting times of the cement pastes, measured using Gilmore needles technique, showed that ZnSrCPC sets faster than ZnCPC. The measured values of the wet strength after 48 h of immersion in PBS solution at 37 degrees C showed that ZnSrCPC cements are stronger than ZnCPC cements. Human osteosarcoma-derived MG63 cell line proved the nontoxicity of the cement powders, using the resazurin metabolic assay. PMID- 20574980 TI - Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization. AB - Tissue engineering and regenerative medicine have furnished a vast range of modalities to treat either damaged tissue or loss of soft tissue or its function. In most approaches, a temporary porous scaffold is required to support tissue regeneration. The scaffold should be designed such that the turnover synchronizes with tissue remodeling and regeneration at the implant site. Segmented polyester urethanes (PUs) used in this study were based on epsilon-caprolactone (CL) and co monomers D,L-lactide (D,L-L) and gamma-butyrolactone (BL), and 1,4 butanediisocyanate (BDI). In vitro, the PUs were nontoxic and haemocompatible. To test in vivo biocompatibility, the PUs were further processed into porous structures and subcutaneously implanted in rats for a period up to 21 days. Tissue remodeling and scaffold turnover was associated with a mild tissue response. The tissue response was characterized by extensive vascularization through the interconnected pores, with low numbers of macrophages on the edges and stroma formation inside the pores of the implants. The tissue ingrowth appeared to be related to the extent of microphase separation of the PUs and foam morphology. By day 21, all of the PU implants were highly vascularized, confirming the pores were interconnected. Degradation of P(CL/D,L-L)-PU was observed at this time, whereas the other two PU types remained intact. The robust method reported here of manufacturing and processing, good mechanical properties, and in vivo tissue response of the porous P(CL/D,L-L)-PU and PBCL-PU makes them excellent candidates as biomaterials with an application for soft tissue remodeling, for example, for cardiovascular regeneration. PMID- 20574978 TI - Biological and mechanical properties of novel composites based on supramolecular polycaprolactone and functionalized hydroxyapatite. AB - Supramolecular polymers based on quadruple hydrogen-bonding ureido-pyrimidinone (UPy) moieties hold promise as dynamic/stimuli-responsive materials in applications such as tissue engineering. Here, a new class of materials is introduced: supramolecular polymer composites. We show that despite the highly ordered structure and tacticity-dependent nature of hydrogen-bonded supramolecular polymers, the bioactivity of these polymers can be tuned through composite preparation with bioceramics. These novel supramolecular composites combine the superior processability of supramolecular polymers with the excellent bioactivity and mechanical characteristics of bioceramics. In particular, the bioactive composites prepared from supramolecular polycaprolactone and UPy grafted hydroxyapatite (HApUPy) are described that can be easily formed into microporous biomaterials. The compression moduli increased about 40 and 90% upon composite preparation with HAp and HApUPy, respectively, as an indication to improved mechanical properties. These new materials show excellent potential as microporous composite scaffolds for the adhesion and proliferation of rat mesenchymal stem cells (rMSCs) as a first step toward bone regeneration studies; rMSCs proliferate about 2 and 2.7 times faster on the conventional composite with HAp and the supramolecular composite with (HApUPy) than on the neat PCL1250(UPy)(2). PMID- 20574981 TI - Electrospun micro/nanofibrous conduits composed of poly(epsilon-caprolactone) and small intestine submucosa powder for nerve tissue regeneration. AB - Three-dimensional biocompatible and biodegradable scaffolds play important roles in tissue engineering. In this study, fibrous mats composed of electrospun poly(epsilon-caprolactone) (PCL)/small intestine submucosa (SIS) tubes were fabricated with a high degree of longitudinal alignment as a conduit for peripheral nerves. Fourier transform infrared analyses of electrospun PCL/SIS mats with various amounts of SIS showed that the SIS was well embedded within the PCL matrix. The diameter of the PCL/SIS fibers with the 3 wt % of SIS in the PCL solution decreased 40% relative to that of pure PCL fibers due to increased electrical conductivity and decreased surface tension. PCL/SIS (3 wt %) electrospun mats exhibited various synergistic effects, including stronger mechanical properties (Young's modulus = more than 80%) and enhanced hydrophilicity (water contact angle at 30 min = 54 degrees ) relative to pure PCL (water contact angle at 30 min = 142 degrees ). Cell attachment and proliferation experiments demonstrated that the interactions between nerve cells (PC-12) and the PCL/SIS conduits were more favorable than those between PC-12 cells and a pure PCL conduit. This study contributes to the understanding of the effects of including SIS in electrospun composite mats. The ability to fabricate highly aligned tubes of PCL/SIS with appropriate mechanical properties and cellular interactions shows great potential for the design of nerve regeneration conduits. PMID- 20574982 TI - In vivo biodegradation and biocompatibility of PEG/sebacic acid-based hydrogels using a cage implant system. AB - Comprehensive in vivo biodegradability and biocompatibility of unmodified and Arg Gly-Asp (RGD) peptide-modified PEG/sebacic acid-based hydrogels were evaluated and compared to the control material poly(lactide-co-glycolide) (PLGA) using a cage implantation system, as well as direct subcutaneous implantation for up to 12 weeks. The total weight loss after 12 weeks of implantation for unmodified PEGSDA and RGD-modified PEGSDA in the cage was approximately 42% and 52%, respectively, with no statistical difference (p > 0.05). The exudate analysis showed that PEGSDA hydrogels induced minimal inflammatory response up to 21 days following implantation, similar to the controls (empty cage and the cage containing PLGA discs). Histology analysis from direct subcutaneous implantation of the hydrogels and PLGA scaffold showed statistically similar resolution of the acute and chronic inflammatory responses with development of the fibrous capsule between the PEGSDA hydrogels and the control (PLGA). The cage system, as well as the histology analysis, demonstrated that the degradation products of both hydrogels, with or without RGD peptide modification, are biocompatible without statistically significant differences in the inflammatory responses, as compared to PLGA. PMID- 20574983 TI - In vivo evaluation of 13-93 bioactive glass scaffolds with trabecular and oriented microstructures in a subcutaneous rat implantation model. AB - The ability of two groups of 13-93 bioactive glass scaffolds to support tissue ingrowth was evaluated after implantation for 4 weeks into subcutaneous pockets in the dorsum of Fisher 344 rats. One group of scaffolds (porosity = 85%; pore size = 100-500 microm) had a "trabecular" microstructure similar to that of dry human trabecular bone, whereas the other group had a "columnar" microstructure of oriented pores (porosity = 65%; pore width = 90-110 microm). Despite the lower porosity and pore width, the columnar scaffolds supported abundant soft tissue ingrowth (glycosaminoglycan and fibrillar stroma), whereas the trabecular scaffolds showed only limited tissue ingrowth. When seeded with mesenchymal stem cells (MSCs), both groups of scaffolds supported abundant tissue infiltration. Bone-like tissue was formed in both groups of scaffolds seeded with MSCs, but not in the scaffolds without MSCs. The new tissues integrated with the hydroxyapatite like surface layer of the scaffolds which resulted from the conversion of the bioactive glass in the body fluids. The results indicate that the trabecular bioactive glass scaffolds seeded with MSCs, as well as the columnar bioactive glass scaffolds, seeded with MSCs or unseeded, could serve as substrates for bone repair and regeneration. PMID- 20574984 TI - Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering. AB - Current bone tissue engineering strategies aim to grow a tissue similar to native bone by combining cells and biologically active molecules with a scaffold material. In this study, a macroporous scaffold made from the seaweed-derived polymer alginate was synthesized and mineralized for cell-based bone tissue engineering applications. Nucleation of a bone-like hydroxyapatite mineral was achieved by incubating the scaffold in modified simulated body fluids (mSBF) for 4 weeks. Analysis using scanning electron microscopy and energy dispersive x-ray analysis indicated growth of a continuous layer of mineral primarily composed of calcium and phosphorous. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue. In addition to the mineral characterization, the ability to control nucleation on the surface, into the bulk of the material, or on the inner pore surfaces of scaffolds was demonstrated. Finally, human MSCs attached and proliferated on the mineralized scaffolds and cell attachment improved when seeding cells on mineral coated alginate scaffolds. This novel alginate- HAP composite material could be used in bone tissue engineering as a scaffold material to deliver cells, and perhaps also biologically active molecules. PMID- 20574985 TI - Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. AB - Systemic primary carnitine deficiency (CDSP) is caused by recessive mutations in the SLC22A5 (OCTN2) gene encoding the plasmalemmal carnitine transporter and characterized by hypoketotic hypoglycemia, and skeletal and cardiac myopathy. The entire coding regions of the OCTN2 gene were sequenced in 143 unrelated subjects suspected of having CDSP. In 70 unrelated infants evaluated because of abnormal newborn screening (NBS) results, 48 were found to have at least 1 mutation/unclassified missense variant. Twenty-eight of 33 mothers whose infants had abnormal NBS results were found to carry at least 1 mutation/unclassified missense variant, including 11 asymptomatic mothers who had 2 mutations. Therefore, sequencing of the OCTN2 gene is recommended for infants with abnormal NBS results and for their mothers. Conversely, 52 unrelated subjects were tested due to clinical indications other than abnormal NBS and only 14 of them were found to have at least one mutation/unclassified variant. Custom designed oligonucleotide array CGH analysis revealed a heterozygous approximately 1.6 Mb deletion encompassing the entire OCTN2 gene in one subject who was apparently homozygous for the c.680G>A (p.R227H) mutation. Thus, copy number abnormalities at the OCTN2 locus should be considered if by sequencing, an apparently homozygous mutation or only one mutant allele is identified. PMID- 20574986 TI - The Alport syndrome COL4A5 variant database. AB - Alport Syndrome is a progressive renal disease with cochlear and ocular involvement. The most common form ( approximately 80%) is inherited in an X linked pattern. X-linked Alport Syndrome (XLAS) is caused by mutations in the type IV collagen alpha chain 5 (COL4A5). We have developed a curated disease specific database containing reported sequence variants in COL4A5. Currently the database archives a total of 520 sequence variants, verified for their position within the COL4A5 gene and named following standard nomenclature. Sequence variants are reported with accompanying information on protein effect, classification of mutation vs. polymorphism, mutation type based on the first description in the literature, and links to pertinent publications. In addition, features of this database include disease information, relevant links for Alport syndrome literature, reference sequence information, and ability to query by various criteria. On-line submission for novel gene variants or updating information on existing database entries is also possible. This free online scientific resource was developed with the clinical laboratory in mind to serve as a reference and repository for COL4A5 variants. PMID- 20574987 TI - A simple low-SAR technique for chemical-shift selection with high-field spin-echo imaging. AB - We have discovered a simple and highly robust method for removal of chemical shift artifact in spin-echo MR images, which simultaneously decreases the radiofrequency power deposition (specific absorption rate). The method is demonstrated in spin-echo echo-planar imaging brain images acquired at 7 T, with complete suppression of scalp fat signal. When excitation and refocusing pulses are sufficiently different in duration, and thus also different in the amplitude of their slice-select gradients, a spatial mismatch is produced between the fat slices excited and refocused, with no overlap. Because no additional radiofrequency pulse is used to suppress fat, the specific absorption rate is significantly reduced compared with conventional approaches. This enables greater volume coverage per unit time, well suited for functional and diffusion studies using spin-echo echo-planar imaging. Moreover, the method can be generally applied to any sequence involving slice-selective excitation and at least one slice-selective refocusing pulse at high magnetic field strengths. The method is more efficient than gradient reversal methods and more robust against inhomogeneities of the static (polarizing) field (B(0)). PMID- 20574988 TI - Ultrashort echo time (UTE) MRI of the lung: assessment of tissue density in the lung parenchyma. AB - Nonuniform disruption of lung architecture is usually assessed by CT, which carries potential radiation risk. Here we report our use of a three-dimensional ultrashort echo time MR method to image the lungs of normal mice at different positive end-expiratory pressures in a 3-T clinical MR system. The ultrashort echo time sequence in conjunction with a projection acquisition of the free induction decay could reduce the echo time to 100 MUsec and provide a more inherent MR signal intensity from the lung parenchyma, which is usually invisible due to its short T*(2) in conventional MRI methods. The signal intensity and T*(2) was reduced as the positive end-expiratory pressure became higher. Further, these parameters were highly correlated to the changes in lung volume (% lung expansion). The results indicated that the MR signal acquired at ultrashort echo time in the lung parenchyma represents interstitial tissue density including blood. The capability of acquiring sufficient MR signal would have implications for the direct assessment of parenchymal architecture in the lung. Therefore, ultrashort echo time imaging may have the potential to assist detection of early and localized pathological destruction of lung tissue architecture observed in various pulmonary disorders such as emphysema without incurring the risks of radiation exposure. PMID- 20574989 TI - Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart. AB - Hyperpolarization of spins via dynamic nuclear polarization (DNP) has been explored as a method to non-invasively study real-time metabolic processes occurring in vivo using (13)C-labeled substrates. Recently, hyperpolarized (13)C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig. Conventional 3D spectroscopic imaging methods require in excess of 100 excitations, making it challenging to acquire a full cardiac-gated, breath-held, whole-heart volume. In this article, the development of a rapid multislice cardiac-gated spiral (13)C imaging pulse sequence consisting of a large flip angle spectral-spatial excitation RF pulse combined with a single-shot spiral k space trajectory for rapid imaging of cardiac metabolism is described. This sequence permits whole-heart coverage (6 slices, 8.8-mm in-plane resolution) in any plane, allowing imaging of the metabolites of interest, [1-(13)C] pyruvate, [1-(13)C] lactate, and (13)C bicarbonate, within a single breathhold. Pyruvate and bicarbonate cardiac volumes were acquired, while lactate images were not acquired due to low lactate levels in the animal model studied. The sequence was demonstrated with phantom experiments and in vivo testing in a pig model. PMID- 20574990 TI - Flow cytometric analysis of genetic FRET detectors containing variable substrate sequences. AB - A genetic Fluorescence Resonance Energy Transfer (FRET) detector undergoes a post translational modification (PTM)-induced conformational change that results in increased FRET. To test if the PTM-dependent FRET change can be quantified by flow cytometry, we purified and immobilized a genetic detector on microbeads and used flow cytometry to measure its FRET efficiency before and after Erk-2 mediated phosphorylation. The fluorescence ratio R between the acceptor and donor fluorescence, which was obtained by fitting a straight line through the data points in linear space, increases following phosphorylation, thus demonstrating that flow cytometry is capable of detecting a PTM-dependent FRET response. Furthermore, when Erk-2 and a genetic detector are coexpressed in bacteria, the measured R value changes with the substrate sequence with near single residue resolution. Similarly, the cells coexpressing the glycosylating enzyme O-GlcNAc transferase (OGT) and a genetic detector specific for OGT exhibit a PTM-induced change in FRET efficiency. Therefore, the combination of flow cytometry and a genetic detector may be useful to characterize the substrate specificity of a PTM enzyme and identify the sequences that are preferentially targeted for PTM in vivo. PMID- 20574991 TI - RF excitation using time interleaved acquisition of modes (TIAMO) to address B1 inhomogeneity in high-field MRI. AB - As the field strength and, therefore, the operational frequency in MRI is increased, the wavelength approaches the size of the human head/body, resulting in wave effects, which cause signal decreases and dropouts. Several multichannel approaches have been proposed to try to tackle these problems, including RF shimming, where each element in an array is driven by its own amplifier and modulated with a certain (constant) amplitude and phase relative to the other elements, and Transmit SENSE, where spatially tailored RF pulses are used. In this article, a relatively inexpensive and easy to use imaging scheme for 7 Tesla imaging is proposed to mitigate signal voids due to B(1)(+) field inhomogeneity. Two time-interleaved images are acquired using a different excitation mode for each. By forming virtual receive elements, both images are reconstructed together using GRAPPA to achieve a more homogeneous image, with only small SNR and SAR penalty in head and body imaging at 7 Tesla. PMID- 20574992 TI - N-isopropylacrylamide-based thermoresponsive polyelectrolyte multilayer films for human mesenchymal stem cell expansion. AB - Human mesenchymal stem cells (hMSCs) are colony-forming unit fibroblasts (CFU-F) derived from adult bone marrow and have significant potential for many cell-based tissue-engineering applications. Their therapeutic potential, however, is restricted by their diminishing plasticity as they are expanded in culture. In this study, we used N-isopropylacrylamide (NIPAM)-based thermoresponsive polyelectrolyte multilayer (N-PEMU) films as culture substrates to support hMSC expansion and evaluated their effects on cell properties. The N-PEMU films were made via layer-by-layer adsorption of thermoresponsive monomers copolymerized with charged monomers, positively charged allylamine hydrochloride (PAH), or negatively charged styrene sulfonic acid (PSS) and compared to fetal bovine serum (FBS) coated surfaces. Surface charges were shown to alter the extracellular matrix (ECM) structure and subsequently regulate hMSC responses including adhesion, proliferation, integrin expression, detachment, and colony forming ability. The positively charged thermal responsive surfaces improved cell adhesion and growth in a range comparable to control surfaces while maintaining significantly higher CFU-F forming ability. Immunostaining and Western blot results indicate that the improved cell adhesion and growth on the positively charged surfaces resulted from the elevated adhesion of ECM proteins such as fibronectin on the positively charge surfaces. These results demonstrate that the layer-by-layer approach is an efficient way to form PNIPAM-based thermal responsive surfaces for hMSC growth and removal without enzymatic treatment. The results also show that surface charge regulates ECM adhesion, which in turn influences not only cell adhesion but also CFU-forming ability and their multi lineage differentiation potential. PMID- 20574994 TI - Synthesis, characterization, and molecular modeling of a pharmaceutical co crystal: (2-chloro-4-nitrobenzoic acid):(nicotinamide). AB - The active pharmaceutical ingredient 2-chloro-4-nitrobenzoic acid (2c4n) is a potentially novel therapy for immunodeficiency diseases as an anti-viral and anti cancer agent, and exists as a dimorph in the solid state. The Kofler hot stage contact method was employed to investigate the potential of preparing a co crystal with nicotinamide (nic), a GRAS compound. The 1:1 co-crystal 1 was made using liquid-assisted grinding and solution crystallization experiments. The crystal structure determination of 1 reveals that the two molecules are associated via a carboxylic acid-pyridine hydrogen bond, while the nic forms a centrosymmetric R2(2)(8) dimer to ultimately form a ribbon architecture which is compared to other known co-crystals of nic. The melting point of the co-crystal is higher than the melting points of either of the pure components, indicating that the pharmaceutical co-crystal is thermally more stable than the pure pharmaceutical compound. The relative stability of the interactions in the co crystal over the pure compounds is further supported by molecular modeling calculations. PMID- 20574993 TI - Serum starvation improves transient transfection efficiency in differentiating embryonic stem cells. AB - Control of genetic expression is a critical issue in the field of stem cell biology, where determining a cell fate or reprogramming adult somatic cells into pluripotent cells has become a common experimental practice. In turn, for these cells to have therapeutic clinical potential, techniques for controlling gene expression are needed that minimizes or eliminates the risk of oncogenesis and mutagenesis. Possible routes for achieving this outcome could come in the form of a transient nonviral gene delivery system. In this study, we improved the efficiency of transient gene delivery to differentiating murine embryonic stem (ES) cells via serum starvation for 3 days before transfection. The transient expression of a constitutively-controlled plasmid increased from ~50% (replated control) to ~83% when transfected after 3 days of serum starvation but decreased to ~28% when transfected after 3 days in normal high serum-containing media. When probed with a liver-specific reporter, Cyp7A1, expression increased from ~1.4% (replated control) to ~3.7% when transfected after 3 days of serum starvation but decreased to ~0.7% when transfected after 3 days in high serum-containing media. Cy3-tagged oligonucleotides were used to rapidly quantify DNA uptake and predict ultimate transfection efficiency. This study suggests that modifications in media serum levels before transfection can have a profound effect on improving nonviral gene delivery. PMID- 20574995 TI - Ivermectin interacts with human ABCG2. AB - Ivermectin is an antiparasitic drug frequently administered to humans. It has a limited brain exposure that is attributed to the efflux activity of ABCB1/Abcb1. ABCG2/Abcg2 is also a major transporter present in most pharmacologically important barriers. However, interaction of ivermectin with Abcg2 shows species specificity and in many studies was confounded by the masking effect of ABCB1/Abcb1. In this study using cellular and membrane assays we show that ivermectin displays a high-affinity interaction with human ABCG2 with IC(50) values in the 1-1.5 uM range. This interaction may have implications in human ABCG2-mediated drug-drug interactions of ivermectin. PMID- 20574996 TI - A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance. AB - The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. PMID- 20574997 TI - Precipitation of a poorly soluble model drug during in vitro lipolysis: characterization and dissolution of the precipitate. AB - Precipitation of cinnarizine during in vitro lipolysis of a self-microemulsifying drug delivery system (SMEDDS) was characterized to gain a better understanding of the mechanisms behind the precipitation. During in vitro lipolysis of the SMEDDS with or without cinnarizine, samples were taken at several timepoints and ultracentrifuged. Cinnarizine content in the pellet increased from 4% to 59% during lipolysis. The precipitation of cinnarizine during in vitro lipolysis correlated well with the degree of lipid digestion, determined by sodium hydroxide addition. The pellet from the endpoint of lipolysis was isolated and subjected to dissolution in biorelevant media. Dissolution rate of cinnarizine from pellets containing precipitated cinnarizine was initially 10-fold higher than dissolution from blank pellet spiked with crystalline cinnarizine, reaching more than 50% drug dissolved in the first minute. Pellets were further characterized by X-ray powder diffraction (XRPD) and polarized light microscopy (PLM). Both methods indicated the presence of liquid crystalline phases of calcium fatty acid soaps, but no presence of crystalline cinnarizine in the pellet. Overall, dissolution studies along with XRPD and PLM analysis indicate that cinnarizine precipitating during in vitro lipolysis of this SMEDDS is not crystalline, suggesting an either amorphous form or a molecular dispersion. PMID- 20574998 TI - A red zwitterionic co-crystal of acetaminophen and 2,4-pyridinedicarboxylic acid. AB - We report on a co-crystal of acetaminophen (APAP) and 2,4-pyridinedicarboxylic acid (PDA). The co-crystal was discovered by screening using the solution mediated phase transformation (SMPT) technique. Despite the bulk solids of each component being white in color, the new co-crystal phase exhibited a red color. The new phase was analyzed using single-crystal X-ray diffraction and identified as (APAP).(PDA).(1). Structural analysis revealed PDA to exist in a hitherto unreported zwitterionic form in the co-crystal. A structural analysis of pure PDA revealed the presence of the zwitterion form in (PDA).(H(2)O) (2), as well. The components of 1 self-assemble as a three-dimensional (3D) hydrogen-bonded network with a pronounced 2D structure. The origin of the red color was investigated using density functional theory calculations, which demonstrate a decreasing pi pi(*) separation involving the components of the solid. PMID- 20574999 TI - Water sorption induced transformations in crystalline solid surfaces: characterization by atomic force microscopy. AB - The effect of water sorption on the mobility of molecules on the surface of a crystalline anhydrous solid was investigated to understand the mechanism of its transformation to the corresponding hydrate. Theophylline was chosen as the model compound. The transition water activity for anhydrate to hydrate transformation, RH(T), and the deliquescence RH, RH(0), was determined to be 62% and 99%, respectively (25 degrees C). Atomic force microscopy (AFM) was used to study the surface changes of theophylline above and below the transition water activity. Contact-mode AFM showed that the jump-to-contact distance increased appreciably above RH(T), suggesting formation of solution on the surface. At RH(T) < RH < RH(0), using dynamic (AC/"tapping" mode) AFM, the movements of surface steps were visualized. These results from AFM indicated that, below RH(0), the formation of a thin solution film significantly increased surface mobility. Furthermore, when the anhydrate crystal surface was seeded with the hydrate, the propagation of a new hydrate phase was observed by polarized light microscopy. In conclusion, atomic force microscopy provided direct evidence that the phase transformation of anhydrous theophylline to theophylline monohydrate in the solid-state is mediated by a surface solution as a result of water adsorption. PMID- 20575000 TI - Development of a targeted polymorph screening approach for a complex polymorphic and highly solvating API. AB - Elucidation of the most stable form of an active pharmaceutical ingredient (API) is a critical step in the development process. Polymorph screening for an API with a complex polymorphic profile can present a significant challenge. The presented case illustrates an extensively polymorphic compound with an additional propensity for forming stable solvates. In all, 5 anhydrous forms and 66 solvated forms have been discovered. After early polymorph screening using common techniques yielded mostly solvates and failed to uncover several key anhydrous forms, it became necessary to devise new approaches based on an advanced understanding of crystal structure and conformational relationships between forms. With the aid of this analysis, two screening approaches were devised which targeted high-temperature desolvation as a means to increase conformational populations and enhance overall probability of anhydrous form production. Application of these targeted approaches, comprising over 100 experiments, produced only the known anhydrous forms, without appearance of any new forms. The development of these screens was a critical and alternative approach to circumvent solvation issues associated with more conventional screening methods. The results provided confidence that the current development form was the most stable polymorph, with a low likelihood for the existence of a more-stable anhydrous form. PMID- 20575001 TI - Enantiomeric 3-chloromandelic acid system: binary melting point phase diagram, ternary solubility phase diagrams and polymorphism. AB - A systematic study of binary melting point and ternary solubility phase diagrams of the enantiomeric 3-chloromandelic acid (3-ClMA) system was performed under consideration of polymorphism. The melting point phase diagram was measured by means of thermal analysis, that is, using heat-flux differential scanning calorimetry (DSC). The results reveal that 3-ClMA belongs to the racemic compound forming systems. Polymorphism was found for both the enantiomer and the racemate as confirmed by X-ray powder diffraction analysis. The ternary solubility phase diagram of 3-ClMA in water was determined between 5 and 50 degrees C by the classical isothermal technique. The solubilities of the pure enantiomers are extremely temperature-dependent. The solid-liquid equilibria of racemic 3-ClMA are not trivial due to the existence of polymorphism. The eutectic composition in the chiral system changes as a function of temperature. Further, solubility data in the alternative solvent toluene are also presented. PMID- 20575002 TI - Investigation of solution and vapor phase mediated phase transformation in thiamine hydrochloride. AB - Thiamine hydrochloride (THCl) can exist as an anhydrate (AH), a hemihydrate (HH) and as a nonstoichiometric hydrate (NSH) where the water content can range between 0 and approximately 1 mole of water per mole of THCl. We have investigated the NSH --> HH phase transformation, in the presence of microcrystalline cellulose (MCC), following (i) wet massing, (ii) fluid-bed granulation, and (iii) exposure to water vapor (40 degrees C/75% RH). Based on Raman spectroscopy (40 degrees C), wet massing of NSH alone caused near complete transformation to HH in <100 min. In the presence of MCC, the transformation rate was decelerated. During fluid-bed granulation, approximately 20% of NSH was transformed to HH and the deceleratory effect of MCC was much less pronounced. Exposure to water vapor, of both NSH-MCC powder blends and granules (prepared by fluid-bed) resulted in complete HH formation within 6 days. Presence of MCC in the powder blend did not affect HH formation kinetics, but facilitated phase transformation in the granules. NSH --> HH conversion appeared to follow two dimensional nucleation and growth model in powder blends, whereas the granules showed either three-dimensional diffusion controlled or a first-order kinetics. In a wet mass, polyvinyl pyrrolidone, a widely used binder, was much more effective than MCC in inhibiting HH formation during wet massing. PMID- 20575004 TI - Comminution of carbohydrate and protein microparticles on firing in a ballistic powder injector. AB - The comminution of various powders produced by either spray-freeze-drying (SFD) or spray-drying (SD) on firing in a Ballistic powder injector could be evaluated quantitatively using light microscopic particle imaging. SFD lactose was damaged much less than SFD mannitol and was caused by greater mechanical strength and lower acceleration. SD lactose or mannitol showed much reduced comminution because of their low porosity. SFD lactose/mannitol/dextran 10 kDa formulations also showed less low comminution. The inclusion of catalase further reduced damage on firing. The extent of comminution on firing was found to be related to microparticle surface structure and porosity which influences both mechanical strength and acceleration. PMID- 20575005 TI - Physicochemical properties of the amorphous drug, cast films, and spray dried powders to predict formulation probability of success for solid dispersions: etravirine. AB - Solid dispersion technology represents an enabling approach to formulate poorly water-soluble drugs. While providing for a potentially increased oral bioavailability secondary to an increased drug dissolution rate, amorphous dispersions can be limited by their physical stability. The ability to assess formulation risk in this regard early in development programs can not only help in guiding development strategies but can also point to critical design elements in the configuration of the dosage form. Based on experience with a recently approved solid dispersion-based product, Intelence(r) (etravirine), a three part strategy is suggested to predict early formulate-ability of these systems. The components include an assessment of the amorphous form, a study of binary drug/carrier cast films and the evaluation of a powder of the drug and polymer processed in a manner relevant to the intended final dosage form. A variety of thermoanalytical, spectroscopic, and spectrophotometric approaches were applied to study the prepared materials. The data suggest a correlation between the glass forming ability and stability of the amorphous drug and the nature of the final formulation. Cast films can provide early information on miscibility and stabilization and assessment of processed powders can help define requirements and identify issues with potential final formulations. PMID- 20575006 TI - Activity-dependent intracellular chloride accumulation and diffusion controls GABA(A) receptor-mediated synaptic transmission. AB - In the CNS, prolonged activation of GABA(A) receptors (GABA(A)Rs) has been shown to evoke biphasic postsynaptic responses, consisting of an initial hyperpolarization followed by a depolarization. A potential mechanism underlying the depolarization is an acute chloride (Cl(-)) accumulation resulting in a shift of the GABA(A) reversal potential (E(GABA)). The amount of GABA-evoked Cl(-) accumulation and accompanying depolarization depends on presynaptic and postsynaptic properties of GABAergic transmission, as well as on cellular morphology and regulation of Cl(-) intracellular concentration ([Cl(-)](i)). To analyze the influence of these factors on the Cl(-) and voltage behavior, we studied spatiotemporal dynamics of activity-dependent [Cl(-)](i) changes in multicompartmental models of hippocampal cells based on realistic morphological data. Simulated Cl(-) influx through GABA(A) Rs was able to exceed physiological Cl(-) extrusion rates thereby evoking HCO(3)(-) -dependent E(GABA) shift and depolarizing responses. Depolarizations were observed in spite of GABA(A) receptor desensitization. The amplitude of the depolarization was frequency dependent and determined by intracellular Cl(-) accumulation. Changes in the dendritic diameter and in the speed of GABA clearance in the synaptic cleft were significant sources of depolarization variability. In morphologically reconstructed granule cells subjected to an intense GABAergic background activity, dendritic inhibition was more affected by accumulation of intracellular Cl(-) than somatic inhibition. Interestingly, E(GABA) changes induced by activation of a single dendritic synapse propagated beyond the site of Cl(-) influx and affected neighboring synapses. The simulations suggest that E(GABA) may differ even along a single dendrite supporting the idea that it is necessary to assign E(GABA) to a given GABAergic input and not to a given neuron. PMID- 20575003 TI - Drug delivery trends in clinical trials and translational medicine: challenges and opportunities in the delivery of nucleic acid-based therapeutics. AB - The ability to deliver nucleic acids (e.g., plasmid DNA, antisense oligonucleotides, siRNA) offers the potential to develop potent vaccines and novel therapeutics. However, nucleic acid-based therapeutics are still in their early stages as a new category of biologics. The efficacy of nucleic acids requires that these molecules be delivered to the interior of the target cell, which greatly complicates delivery strategies and compromises efficiency. Due to the safety concerns of viral vectors, synthetic vectors such as liposomes and polymers are preferred for the delivery of nucleic acid-based therapeutics. Yet, delivery efficiencies of synthetic vectors in the clinic are still too low to obtain therapeutic levels of gene expression. In this review, we focus on some key issues in the field of nucleic acid delivery such as PEGylation, encapsulation and targeted delivery and provide some perspectives for consideration in the development of improved synthetic vectors. PMID- 20575007 TI - GSK3beta overexpression induces neuronal death and a depletion of the neurogenic niches in the dentate gyrus. AB - Overexpression of GSK3beta in transgenic mice induces learning deficits and some features associated with Alzheimer's disease (AD), including dentate gyrus (DG) atrophy. Here, we assessed whether these mice also recapitulate DG atrophy as well as impaired neurogenesis reported in AD. Ultrastructural analysis revealed that there were fewer and more disorganized neurogenic niches in these animals, coupled with an increase in the proportion of immature neurons. Indeed, the maturation of granule cells is delayed as witnessed by the alterations to the length and patterning of their dendritic trees and to the mossy fiber terminals. Together with an increase in neuronal death, these phenomena lead to a marked decrease in the number and disorganization of granule cells of the DG. Our results suggest that GSK3beta overexpression perturbs proliferation and maturation, resulting in the loss of immature neurons. In turn, the activation of microglia is stimulated in conjunction with a decrease in the birth of new functional neurons, leading to the deterioration of this structure. These data support the idea that by inducing degeneration of the DG, GSK3beta could be involved in the pathogenesis of AD. PMID- 20575009 TI - De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature. AB - The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype. PMID- 20575008 TI - Projections to the anterodorsal thalamus and lateral mammillary nuclei arise from different cell populations within the postsubiculum: implications for the control of head direction cells. AB - The neural representation of directional heading is encoded by a population of cells located in a circuit that includes the postsubiculum (PoS), anterodorsal thalamus (ADN), and lateral mammillary nuclei (LMN). Throughout this circuit, many cells rely on both movement- and landmark-related information to discharge as a function of the animal's directional heading. The PoS projects to both the ADN and LMN, and these connections may convey critical spatial information about landmarks, because lesions of the PoS disrupt landmark control in head direction (HD) cells and hippocampal place cells [Goodridge and Taube (1997) J Neurosci 17:9315-9330; Calton et al. (2003) J Neurosci 23:9719-9731]. The PoS -> ADN projection originates in the deep layers of PoS, but no studies have determined whether the PoS -> LMN projection originates from the same cells that project to ADN. To address this issue, two distinct cholera toxin-subunit B (CTB) fluorophore conjugates (Alexa Fluor 488 and Alexa Fluor 594) were injected into the LMN and ADN of the same rats, and PoS sections were examined for cell bodies containing either or both CTB conjugates. Results indicated that the PoS -> LMN projection originates exclusively from a thin layer of cells located superficial to the layer(s) of PoS -> ADN projection cells, with no overlap. To verify the laminar distribution and morphological characteristics of PoS -> LMN and PoS -> ADN cells, biotinylated dextran amine was injected into LMN or ADN of different rats, and tissue sections were counterstained with thionin. Results indicated that the PoS -> LMN projection arises from large pyramidal cells in layer IV, whereas the PoS -> ADN projection arises from a heterogeneous cell population in layers V/VI. This study provides the first evidence that the PoS -> ADN and PoS > LMN projections arise from distinct, nonoverlapping cell layers in PoS. Functionally, the PoS may provide landmark information to HD cells in LMN. PMID- 20575010 TI - Computational studies on the mechanism and kinetics of Cl reaction with C2H5I. AB - The dual-level direct kinetics method has been used to investigate the multichannel reactions of C(2)H(5)I + Cl. Three hydrogen abstraction channels and one displacement process are found for the title reaction. The calculation indicates that the hydrogen abstraction from -CH(2)- group is the dominant reaction channel, and the displacement process may be negligible because of the high barrier. The rate constants for individual reaction channels are calculated by the improved canonical variational transition-state theory with small curvature tunneling correction over the temperature range of 220-1500 K. Our results show that the tunneling correction plays an important role in the rate constant calculation in the low-temperature range. Agreement between the calculated and experimental data available is good. The Arrhenius expression k(T) = 2.33 x 10(-16) T(1.83) exp(-185.01/T) over a wide temperature range is obtained. Furthermore, the kinetic isotope effects for the reaction C(2)H(5)I + Cl are estimated so as to provide theoretical estimation for future laboratory investigation. PMID- 20575011 TI - A theoretical study on the catalytic mechanism of Mus musculus adenosine deaminase. AB - The catalytic mechanism of Mus musculus adenosine deaminase (ADA) has been studied by quantum mechanics and two-layered ONIOM calculations. Our calculations show that the previously proposed mechanism, involving His238 as the general base to activate the Zn-bound water, has a high activation barrier of about 28 kcal/mol at the proposed rate-determining nucleophilic addition step, and the corresponding calculated kinetic isotope effects are significantly different from the recent experimental observations. We propose a revised mechanism based on calculations, in which Glu217 serves as the general base to abstract the proton of the Zn-bound water, and the protonated Glu217 then activates the substrate for the subsequent nucleophilic addition. The rate-determining step is the proton transfer from Zn-OH to 6-NH(2) of the tetrahedral intermediate, in which His238 serves as a proton shuttle for the proton transfer. The calculated kinetic isotope effects agree well with the experimental data, and calculated activation energy is also consistent with the experimental reaction rate. PMID- 20575012 TI - Theoretical investigation of an energetic fullerene derivative. AB - A self-consistent estimation method for the thermochemical properties of N-methyl 3-(2',4',6'-trinitrobenzene)-fulleropyrrolidine (MTNBFP) is presented. This method is based on enthalpy of formation (Delta(f)H(m)(minus sign in circle)) and enthalpy of combustion obtained from BLYP/DNP calculations of the total energies and frequencies for MTNBFP. The enthalpy of formation was calculated by an optimized set of isodesmic reactions given the available experimental Delta(f)H(m)(minus sign in circle) of relative compounds. MTNBFP has a high enthalpy of formation, 2782.2 kJ/mol. Detonation velocity and detonation pressure were also presented in terms of Kamlet and Jacobs equations. Drop hammer impact sensitivity tests and blasting point per 5 s tests indicate MTNBFP may be a potential candidate primary explosive. To understand the test results well, we proposed a series of chemical reaction mechanisms and interpreted the relationship between impact sensitivity and electronic structures from the viewpoint of nitro group charge, electrostatic potential, and vibrational modes. PMID- 20575013 TI - Multidimensionality of delocalization indices and nucleus-independent chemical shifts in polycyclic aromatic hydrocarbons II: proof of further nonlocality. AB - In a recent contribution, we examined the effect of 10- and 14-center circuits on the nucleus-independent chemical shifts NICSs using multicenter bond indices (MCBIs) (Fias et al., J Comput Chem 2008, 29, 358). In this study, the nonlocal contributions to the NICS are further investigated for a larger set of polycyclic aromatic hydrocarbons (PAHs). To achieve this, the NICSs are predicted using the MCBI and compared with ab initio results. The NICSs of the central ring of perylene- and benzo-[ghi]perylene-like fragments and of coronene appear to have other nonlocal contributions than the ones previously studied. It is shown that a model based on the MCBI-ring current maps and the inclusion of new circuits proves the existence and shows the nature of these new nonlocal effects on the NICS. This new model leads to a better understanding of the differences between the NICSs and delocalization indices. The results show that the NICS value is not only significantly influenced by the higher order circuits encircling the ring at which it is evaluated but also by the local aromaticity of the surrounding rings, and occasionally, like in the case of coronene, the NICSs are even influenced by currents farther away in the molecule. PMID- 20575014 TI - Branch migration of Holliday junction in RuvA tetramer complex studied by umbrella sampling simulation using a path-search algorithm. AB - Branch migration of the Holliday junction takes place at the center of the RuvA tetramer. To elucidate how branch migration occurs, umbrella sampling simulations were performed for complexes of the RuvA tetramer and Holliday junction DNA. Although conventional umbrella sampling simulations set sampling points a priori, the umbrella sampling simulation in this study set the sampling points one by one in order to search for a realistic path of the branch migration during the simulations. Starting from the X-ray structure of the complex, in which the hydrogen bonds between two base-pairs were unformed, the hydrogen bonds between the next base-pairs of the shrinking stems were observed to start to disconnect. At the intermediate stage, three or four of the eight unpaired bases interacted closely with the acidic pins from RuvA. During the final stage, these bases moved away from the pins and formed the hydrogen bonds of the new base-pairs of the growing stems. The free-energy profile along this reaction path showed that the intermediate stage was a meta-stable state between two free-energy barriers of about 10 to 15 kcal/mol. These results imply that the pins play an important role in stabilizing the interactions between the pins and the unpaired base-pairs. PMID- 20575015 TI - Polarizable empirical force field for sulfur-containing compounds based on the classical Drude oscillator model. AB - Condensed-phase computational studies of molecules using molecular mechanics approaches require the use of force fields to describe the energetics of the systems as a function of structure. The advantage of polarizable force fields over nonpolarizable (or additive) models lies in their ability to vary their electronic distribution as a function of the environment. Toward development of a polarizable force field for biological molecules, parameters for a series of sulfur-containing molecules are presented. Parameter optimization was performed to reproduce quantum mechanical and experimental data for gas phase properties including geometries, conformational energies, vibrational spectra, and dipole moments as well as for condensed phase properties such as heats of vaporization, molecular volumes, and free energies of hydration. Compounds in the training set include methanethiol, ethanethiol, propanethiol, ethyl methyl sulfide, and dimethyl disulfide. The molecular volumes and heats of vaporization are in good accordance with experimental values, with the polarizable model performing better than the CHARMM22 nonpolarizable force field. Improvements with the polarizable model were also obtained for molecular dipole moments and in the treatment of intermolecular interactions as a function of orientation, in part due to the presence of lone pairs and anisotropic atomic polarizability on the sulfur atoms. Significant advantage of the polarizable model was reflected in calculation of the dielectric constants, a property that CHARMM22 systematically underestimates. The ability of this polarizable model to accurately describe a range of gas and condensed phase properties paves the way for more accurate simulation studies of sulfur-containing molecules including cysteine and methionine residues in proteins. PMID- 20575016 TI - Application of ant colony optimization in development of models for prediction of anti-HIV-1 activity of HEPT derivatives. AB - Quantitative structure-activity relationship models were derived for 107 analogs of 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine, a potent inhibitor of the HIV-1 reverse transcriptase. The activities of these compounds were investigated by means of multiple linear regression (MLR) technique. An ant colony optimization algorithm, called Memorized_ACS, was applied for selecting relevant descriptors and detecting outliers. This algorithm uses an external memory based upon knowledge incorporation from previous iterations. At first, the memory is empty, and then it is filled by running several ACS algorithms. In this respect, after each ACS run, the elite ant is stored in the memory and the process is continued to fill the memory. Here, pheromone updating is performed by all elite ants collected in the memory; this results in improvements in both exploration and exploitation behaviors of the ACS algorithm. The memory is then made empty and is filled again by performing several ACS algorithms using updated pheromone trails. This process is repeated for several iterations. At the end, the memory contains several top solutions for the problem. Number of appearance of each descriptor in the external memory is a good criterion for its importance. Finally, prediction is performed by the elitist ant, and interpretation is carried out by considering the importance of each descriptor. The best MLR model has a training error of 0.47 log (1/EC(50)) units (R(2) = 0.90) and a prediction error of 0.76 log (1/EC(50)) units (R(2) = 0.88). PMID- 20575017 TI - Multiple myeloma with lacrimal gland amyloidosis and sarcoidosis. PMID- 20575018 TI - Multiple intra-abdominal masses. PMID- 20575019 TI - Peripheral blood and bone marrow morphology in adult T-cell leukaemia/lymphoma. PMID- 20575021 TI - Primary pulmonary non-Hodgkin's lymphoma: a retrospective analysis of 29 cases in a Chinese population. PMID- 20575022 TI - The outcome of IgD myeloma after autologous hematopoietic stem cell transplantation is similar to other Ig subtypes. AB - IgD myeloma is a rare subtype of myeloma that is associated with an aggressive course, resistance to chemotherapy, and a poor outcome. We identified 17 patients with IgD myeloma, who received a hematopoietic stem cell transplantation (HCT) at our institution between August 1988 and June 2008. Fifteen of these 17 patients underwent an autologous (auto) HCT. Complete responses (CRs) were seen in 6 of 15 (40%) patients; three converted from partial response to CR, two from minimal response to CR, and one from very good partial response to CR. The overall response rate after auto HCT was 86% (13 of 15). Kaplan-Meiers estimates of 3 year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median PFS and OS were 18 and 45 months, respectively. These results were comparable with patients receiving autologous HCT for other Ig subtypes of myeloma. PMID- 20575023 TI - Clinical manifestations of combined factor V and VIII deficiency: a series of 37 cases from a single center in India. PMID- 20575024 TI - Analysis of the REL, BCL11A, and MYCN proto-oncogenes belonging to the 2p amplicon in chronic lymphocytic leukemia. PMID- 20575025 TI - Pulmonary embolism in Black Americans. PMID- 20575027 TI - An unusual nodal marginal zone lymphoma with bright CD10 expression: a potential diagnostic pitfall. PMID- 20575028 TI - Polycythemia vera-associated acquired von Willebrand syndrome despite near-normal platelet count. PMID- 20575029 TI - Expression of CD1d and presence of invariant NKT cells in classical Hodgkin lymphoma. PMID- 20575031 TI - ZAP-70 expression is associated with increased risk of autoimmune cytopenias in CLL patients. AB - Autoimmune cytopenias (AIC) are frequent in chronic lymphocytic leukemia (CLL) patients, but risk factors and prognostic relevance of these events are controversial. Data about the influence on AIC of biological prognostic markers, as ZAP-70, are scanty. We retrospectively evaluated AIC in 290 CLL patients tested for ZAP-70 expression by immunohistochemistry on bone marrow biopsy at presentation. They were 185 men, median age 63 years, 77.9% Binet stage A, 17.6% B and 4.5% C. AIC occurred in 46 patients (16%): 31 autoimmune hemolytic anemias, 10 autoimmune thrombocytopenias, four Evans syndromes, and one pure red cell aplasia. Of the 46 cases of AIC, 37 (80%) occurred in ZAP-70 positive patients and nine (20%) in ZAP-70 negatives. ZAP-70 expression [Hazard Ratio (HR) = 7.42; 95% confidence interval (CI): 2.49-22.05] and age >65 years (HR = 5.41; 95% CI: 1.67-17.49) resulted independent risk factors for AIC. Among the 136 patients evaluated both for ZAP-70 expression and IGHV status, the occurrence of AIC was higher in ZAP-70 positive/IGHV unmutated cases (35%) than in patients ZAP-70 negative/IGHV mutated (6%) or discordant for the two parameters (4%; P < 0.0001). In ZAP-70 positive patients, occurrence of AIC negatively influenced survival (HR = 1.75; 95% CI: 1.06-2.86). The high risk of developing AIC in ZAP-70 positive CLL, particularly when IGHV unmutated, should be considered in the clinical management. PMID- 20575032 TI - A specific linkage between the incidence of TP53 mutations and type of chromosomal translocations in B-precursor acute lymphoblastic leukemia cell lines. PMID- 20575033 TI - Analysis of von Willebrand factor structure by multimer analysis. AB - Analysis of von Willebrand factor (VWF) structure is achieved by performing a highly specialized procedure, VWF multimer analysis. The test is reserved for the reference or specialized laboratory environment. The assay is qualitative (though under some circumstances multimers may be quantified) in that it assesses the overall size distribution of VWF multimers as well as their individual internal structure. The test is used predominantly to type or subtype von Willebrand disease. The analysis of VWF multimers generally consists of four steps: (1) electrophoresis of plasma in an agarose gel, (2) either gel fixation or transfer of the electrophoretic protein product to a membrane, (3) immunodetection of the protein, and (4) evaluation of the protein in the gel or membrane. The assay is complex, time consuming, requires specialized equipment and technical expertise, and is not standardized. PMID- 20575034 TI - Pain rate and social circumstances rather than cumulative organ damage determine the quality of life in adults with sickle cell disease. PMID- 20575035 TI - Normal ranges of angiogenesis regulatory proteins in human platelets. AB - Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 +/- 0.37 pg/10(6) platelets); PDGF (23 +/- 6 pg/10(6)); PF4 (12 +/- 5 ng/10(6)); TSP-1 (31 +/- 12 ng/10(6)); bFGF (0.44 +/- 0.15 pg/10(6)); and endostatin (5.6 +/- 3.0 pg/10(6)). There was an excellent correlation (R(2) = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF 4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability. PMID- 20575036 TI - Bortezomib plus intermediate-dose dexamethasone and thalidomide in elderly untreated patients with multiple myeloma: a Chinese experience. AB - Bortezomib has proven to be active in patients with multiple myeloma (MM), including elderly patients. The aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with intermediate-dose dexamethasone (Dex) and thalidomide in untreated MM patients aged > or =65 years in a Chinese single center. In this study, 18 patients were treated with bortezomib at 1.3 mg/m(2) IV on Days 1, 4, 8, and 11 and Dex at 20 mg/day IV on Days 1-4 and 8-11 simultaneously. Thalidomide at dose of 100 mg/day was given everyday. The mean number of cycles of bortezomib treatment was 2.06. Three patients (17%) achieved a complete response (CR), four (22%) a very good partial response (VGPR), and nine (50%) a PR, resulting in an overall response rate of 89%. The median time to response was 22 days (range 14-50 days). The duration of response was significantly longer in patients achieving a CR/VGPR with respect to those achieving only a PR (8.5 vs. 4.2 months, P = 0.03). Grade 3-4 toxicities occurring in patients comprised weakness, thrombocytopenia, diarrhea, infection, and neuropathy. Only one patient suffered from deep vein thrombosis. This preliminary experience in Chinese patients indicated that bortezomib-Dex thalidomide is highly effective in elderly untreated patients with MM, even in patients with poor prognostic features. PMID- 20575037 TI - Comparison of characteristics from White- and Black-Americans with venous thromboembolism: a cross-sectional study. AB - When compared with Whites, Black-Americans may have a 40% higher incidence venous thromboembolism (VTE) incidence. However, whether other VTE characteristics and risk factors vary by race is uncertain. To compare demographic and baseline characteristics among White- and Black-Americans with VTE, we used data prospectively collected from consecutive consenting adults enrolled in seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Centers from August 2003 to March 2009. These characteristics were compared among Whites (n = 2002) and Blacks (n = 395) with objectively diagnosed VTE, both overall, and by age and gender. When compared with Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks were women. Blacks had a significantly higher mean BMI and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE, and documented thrombophilia (solely from reduced factor V Leiden and prothrombin G20210A prevalence). Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV, and sickle cell disease. When compared with White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy. We conclude that Whites and Blacks differ significantly regarding demographic and baseline characteristics that may be risk factors for VTE. The prevalence of transient VTE risk factors and idiopathic VTE among Blacks appears to be lower and higher, respectively, suggesting that heritability may be important in the etiology of VTE among Black Americans. PMID- 20575038 TI - Informational needs assessment of non-Hodgkin lymphoma survivors and their physicians. PMID- 20575039 TI - XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is driven by the BCR-ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR-ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polymorphisms (SNPs) on the nucleotide excision repair (NER) genes (ERCC2-ERCC8, RPA1-RPA3, LIG1, RAD23B, XPA, XPC) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild-type haplotype (499C-939A) was associated with a better response to imatinib. Moreover, the 5-year failure free survival for CA carriers was significantly better than that of the non-CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb < or =11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5-16.1) or a non-CA XPC haplotype (OR = 4.1, 95% CI = 1.6-10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML. PMID- 20575040 TI - A comment on laboratory monitoring of new anticoagulants. PMID- 20575041 TI - Hyperferritinemia and iron overload in type 1 Gaucher disease. AB - Hyperferritinemia occurs in Gaucher disease but its clinical spectrum or its association with systemic iron overload and HFE mutations are not known. In 114 patients with Type 1 Gaucher disease, we determined serum ferritin, transferrin saturation and HFE genotype. The results were correlated with the extent of hepatosplenomegaly, overall Gaucher disease severity score index, and response to enzyme replacement therapy. In a subset of patients with radiological and/or laboratory evidence of systemic iron overload, liver biopsy was performed. There was a mean 3.7-fold elevation of serum ferritin over the upper limit of normal (ULN). Prior splenectomy was associated with most severe hyperferritinemia compared to patients with intact spleen (6.53 x ULN vs. 2.69 x ULN, P = 0.003). HFE genotyping revealed two patients homozygous for H63D mutation and 30% of patients heterozygote carriers of H63D mutation; no patients harbored C282Y mutation; there was no correlation of ferritin with HFE genotype. Ferritin level correlated with liver volume (Pearson correlation coefficient = 0.254, P = 0.035) and it was negatively correlated with hemoglobin (r = -0.315, P = 0.004); there was no relationship with other indicators of Gaucher disease activity. Enzyme replacement therapy (ERT) resulted in amelioration of hyperferritinemia: 707 +/- 898 ng/ml vs. 301 +/- 310 ng/ml (P = 0.001), transferrin saturation remained normal. Three patients were suspected of clinical iron overload, confirmed on liver biopsy. Iron accumulation was variably noted in hepatocytes and Kupffer cells. There is a high prevalence of hyperferritinemia in Type 1 Gaucher disease that is associated with indicators of disease severity, reversed by ERT and is not related to HFE mutations. PMID- 20575042 TI - The assessment of human organic cation transporter 1 (hOCT1) mRNA expression in patients with chronic myelogenous leukemia is affected by the proportion of different cells types in the analyzed cell population. PMID- 20575043 TI - Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML). AB - In older patients suffering from acute myelogenous leukemia (AML), aggressive chemotherapy is accompanied with high treatment-related morbidity and mortality. Gemtuzumab ozogamicin (GO), a humanized monoclonal anti-CD33 antibody, represents a well tolerated treatment option, but optimal treatment schedules are still unknown. Additionally, Suppressor of cytokine signaling 3 (SOCS3) inhibits the CD33-induced block on cytokine-induced proliferation. Consequently, a variable response of AML cells to anti-CD33-targeted therapy may be caused by modulation of SOCS3 expression. Twenty-four patients with refractory or relapsed CD33 positive AML received GO as a single agent before or after conventional chemotherapy. The methylation status of the SOCS3 CpG island was assessed by methylation-specific polymerase chain reaction. Response (RR) and overall survival (OS) were significantly higher in 16 patients receiving chemotherapy before GO (RR 81%, OS 14.8 months) compared to three patients who received GO single agent therapy (RR 33%, OS 7.2 months) or 16 with GO before chemotherapy (RR 0% OS 2.2 months, P = 0.01 for RR and P < 0.001 for OS). Methylation of the SOCS3 CpG island was found in 8/24 patients. There was a trend towards a higher RR and longer OS in patients with SOCS3 hypermethylation (RR 86%, OS 25.1 months) compared to unmethylated SOCS3 (RR 56%, OS 10.3 months, P = 0.09). Administration of GO a few days after chemotherapy seems to provide better response and survival compared to administration of GO directly before chemotherapy. The potential role of SOCS3 hypermethylation as a biomarker should be further investigated in patients undergoing GO containing therapies. PMID- 20575044 TI - Caring for nonhuman primates in biomedical research facilities: scientific, moral and emotional considerations. AB - Animal care for nonhuman primates (NHPs) in biomedical facilities has undergone major changes in the past few decades. Today, most primate facilities have dedicated and highly trained animal care technicians who go to great efforts to ensure the physiological and psychological well being of the primates in their charge. These caretakers work closely with the animals and, as a result, often develop strong relationships with them. Once discouraged and considered a potential threat to scientific objectivity, such positive relationships are now seen as important components to animal care. Positive interactions between caretakers and primates can benefit the primates by reducing their stress and improving their overall well being which can, in turn, help the scientific endeavor. Further, providing the best possible care is our moral responsibility. However, there can also be emotional costs associated with caring for NHPs in research facilities, particularly when animals become ill or have to be euthanized. Facilities can do much to help ease this conflict. High-quality and conscientious animal care is good for the animals, science, and public perception of research facilities. PMID- 20575045 TI - The ontogeny of handling hard-to-process food in wild brown capuchins (Cebus apella apella): evidence from foraging on the fruit of Maximiliana maripa. AB - We examined age-related differences in wild brown capuchins' foraging efficiency and the food-processing behaviors directed toward maripa palm fruit (Maximiliana maripa). A detailed comparison of the different foraging techniques showed that plucking the fruit from the infructescence constituted the main difficulty of this task. Foraging efficiency tended to increase with age, with a threshold at which sufficient strength allowed immatures by the age of three to reach adult level efficiency. Youngsters spent more time than older individuals browsing the infructescence and pulling the fruit in an attempt to harvest it. Infants tried to compensate for their inability to pluck fruit by adopting alternative strategies but with low payback, such as gnawing unplucked fruit and opportunistically scrounging others' partially processed food. Although around 2 years of age, young capuchins exhibited all of the behaviors used by adults, they did not reach adult-level proficiency at feeding on maripa until about 3 years (older juveniles). We compared this developmental pattern with that of extractive foraging on beetle larvae (Myelobia sp.) hidden in bamboo stalks, a more difficult food for these monkeys [Gunst N, Boinski S, Fragaszy DM. Behaviour 145:195-229, 2008]. For maripa, the challenge was mainly physical (plucking the fruit) once a tree was encountered, whereas for larvae, the challenge was primarily perceptual (locating the hidden larvae). For both foods, capuchins practice for years before achieving adult-level foraging competence, and the timeline is extended for larvae foraging (until 6 years) compared with maripa (3 years). The differing combinations of opportunities and challenges for learning to forage on these different foods illustrate how young generalist foragers (i.e. exploiting a large number of animal and plant species) may compensate for their low efficiency in extractive foraging tasks by showing earlier competence in processing less difficult but nutritious foods, such as maripa fruit. PMID- 20575047 TI - Joint Bayesian analysis of birthweight and censored gestational age using finite mixture models. AB - Birthweight and gestational age are closely related and represent important indicators of a healthy pregnancy. Customary modeling for birthweight is conditional on gestational age. However, joint modeling directly addresses the relationship between gestational age and birthweight, and provides increased flexibility and interpretation as well as a strategy to avoid using gestational age as an intermediate variable. Previous proposals have utilized finite mixtures of bivariate regression models to incorporate well-established risk factors into analysis (e.g. sex and birth order of the baby, maternal age, race, and tobacco use) while examining the non-Gaussian shape of the joint birthweight and gestational age distribution. We build on this approach by demonstrating the inferential (prognostic) benefits of joint modeling (e.g. investigation of 'age inappropriate' outcomes like small for gestational age) and hence re-emphasize the importance of capturing the non-Gaussian distributional shapes. We additionally extend current models through a latent specification which admits interval-censored gestational age. We work within a Bayesian framework which enables inference beyond customary parameter estimation and prediction as well as exact uncertainty assessment. The model is applied to a portion of the 2003-2006 North Carolina Detailed Birth Record data (n=336129) available through the Children's Environmental Health Initiative and is fitted using the Bayesian methodology and Markov chain Monte Carlo approaches. PMID- 20575048 TI - A Bayesian approach to competing risks analysis with masked cause of death. AB - Cause-specific analyses under a competing risks framework have received considerable attention in the statistical literature. Such analyses are useful for comparing mortality patterns across racial and/or age groups. Earlier work in the statistical literature focused on the situation when the cause of death is known. A challenging twist to the problem arises when the cause of death is not known exactly, but can be narrowed down to a set of potential causes that do not necessarily act independently. This phenomenon, referred to as masking, is often the result of incomplete or partial information on death certificates and/or lack of routine autopsy on every patient. In this article we propose a semiparametric Bayesian approach for analyzing competing risks survival data with masked cause of death. The models proposed do not assume independence among the causes, and are valid for an arbitrary number of causes. Further, the Bayesian approach is flexible in allowing a general pattern of missingness for the cause of death. We illustrate our methodology using breast cancer data from the Detroit Surveillance, Epidemiology, and End Results registry. PMID- 20575049 TI - Construction of confidence limits about effect measures: a general approach, by G. Y. Zou and A. Donner, Statistics in Medicine 2008; 27:1693-1702. PMID- 20575050 TI - Prediction of onset of crystallization in amorphous pharmaceutical systems: phenobarbital, nifedipine/PVP, and phenobarbital/PVP. AB - The aim of this work is to determine if a stability testing protocol based on the correlations between crystallization onset and relaxation time above the glass transition temperature (T(g)) can be used to predict the crystallization onsets in amorphous pharmaceutical systems well below their T(g). This procedure assumes that the coupling between crystallization onset and molecular mobility is the same above and below T(g). The stability testing protocol has been applied to phenobarbital, phenobarbital/polyvinylpyrrolidone (PVP) (95/5, w/w), and nifedipine/PVP (95/5, w/w). Crystallization onsets have been detected by polarized light microscopy examination of amorphous films; molecular mobility has been determined by dielectric relaxation spectroscopy above T(g) and by both isothermal calorimetry and modulated differential scanning calorimetry below T(g). We find that small amounts of PVP significantly retard re-crystallization. This dramatic effect of PVP is not related to mobility, so this approach applies, at best, to extrapolation of high temperature data on a given formulation to low temperatures. Variation in molecular mobility at these concentrations of PVP is not the dominant factor in determining variation in propensity for re crystallization from glassy systems; we suggest surface interactions between PVP and nuclei and/or small crystals slowing growth control variation in crystallization kinetics between formulations. PMID- 20575051 TI - Oxidized recombinant human growth hormone that maintains conformational integrity. AB - Chemical degradations often induce changes in protein conformation and thus influence protein activity and protein stability in solutions. One difficulty in studying of chemical degradations on protein aqueous properties is to obtain sufficient amount of chemically degraded protein which is well characterized. Chemical degradation protocols that are often used may induce also conformation changes and aggregation of the protein. In this article we studied the effect of methionine oxidation on the conformation of recombinant human growth hormone (r hGH). In literature it is reported that oxidation of methionine residues induces conformation changes on r-hGH. In our study, oxidation of r-hGH was performed by incubation with hydrogen peroxide under mild conditions. Mass spectrometry and chromatographic analysis revealed that oxidation with hydrogen peroxide resulted in more than 90% of oxidized r-hGH. By extensive spectroscopic characterizations no detectable change in conformation and aggregation of r-hGH after oxidation was found. In conclusion, mild oxidation conditions led to selective oxidation of the two more accessible methionine residues of r-hGH (Met(14) and Met(125)) and did not results in any conformation change of the protein. These findings prove that oxidation of human growth hormone does not influence protein conformation and demonstrate the importance of employing mild conditions during production of oxidized protein. PMID- 20575052 TI - Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen. AB - The potential use of nanostructured lipid carriers (NLC) composed of a fatty acid [stearic acid (SA)] or a triglyceride (glyceryl behenate) as solid lipids, and a mixture of medium chain triglycerides and castor oil as liquid lipids, for skin administration of flurbiprofen (FB), has been explored. Two different optimized NLC formulations (FB-SANLC based on SA vs. FB-C888NLC based on glyceryl behenate), with respect to the morphometrical properties (particle size and polydispersity index) and the entrapment efficiency, were used in this study. The ex vivo permeation profiles of FB-C888NLC, FB-SANLC and conventional FB solution were evaluated using human skin. An improved FB permeation was observed when the drug was delivered by skin application of FB-C888NLC, attributed to the particle size and matrix crystallinity. The differential scanning calorimetry and X-ray diffraction studies suggested major polymorphic transitions in the lipid matrix of FB-C888NLC. A good correlation between polymorphic transitions and increased drug permeation was observed. However, both NLC dispersions showed a penetration enhancing ratio (ER) higher than conventional FB solution. The in vitro and in vivo irritancy and local tolerability were assessed by running, respectively, the SKINTEXTM and Draize test. Both FB-C888NLC and FB-SANLC were classified as nonirritant. PMID- 20575053 TI - On the use of mathematical models to build the design space for the primary drying phase of a pharmaceutical lyophilization process. AB - The aim of this article is to show a procedure to build the design space for the primary drying of a pharmaceuticals lyophilization process. Mathematical simulation of the process is used to identify the operating conditions that allow preserving product quality and meeting operating constraints posed by the equipment. In fact, product temperature has to be maintained below a limit value throughout the operation, and the sublimation flux has to be lower than the maximum value allowed by the capacity of the condenser, besides avoiding choking flow in the duct connecting the drying chamber to the condenser. Few experimental runs are required to get the values of the parameters of the model: the dynamic parameters estimation algorithm, an advanced tool based on the pressure rise test, is used to this purpose. A simple procedure is proposed to take into account parameters uncertainty and, thus, it is possible to find the recipes that allow fulfilling the process constraints within the required uncertainty range. The same approach can be effective to take into account the heterogeneity of the batch when designing the freeze-drying recipe. PMID- 20575054 TI - Integrated approach to study the dehydration kinetics of nitrofurantoin monohydrate. AB - There is a need for thorough knowledge of solid-state transformations in order to implement quality by design (QbD) methodology in drug development. The present study was aimed at gaining a mechanistic understanding of the dehydration of nitrofurantoin monohydrate II (NF-MH). The dehydration was studied using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), hot stage microscopy (HSM), and variable temperature X-ray powder diffraction (VT XRPD). Isothermal TGA data were used to study dehydration kinetics using model fitting and model-free approaches. Model-fitting analysis indicated a good fit for several models derived from nucleation-growth and/or geometric contraction mechanisms. However, based on visual observations during HSM, Avrami-Erofeyev equations A3 and A4, indicating nucleation-growth phenomenon, were found to be the most suitable kinetic models. HSM showed initiation of dehydration with random nucleation, and nuclei coalesced with the progress of dehydration reaction. VT-XRPD revealed formation of anhydrate beta form on dehydration of NF MH. The phenomenon of random nucleation is justified based on the crystal structure of NF-MH, which showed presence of water molecules in an isolated manner, prohibiting directional dehydration. It was found that supplementary information from HSM and VT-XRPD can be valuable to gain a better understanding of dehydration from formal solid-state kinetics analysis. PMID- 20575055 TI - Nonhomogeneous distribution of filamentous actin in the presynaptic terminals on the spinal motoneurons. AB - Although actin is known to play important roles in synapses, immunocytochemical and structural studies on synaptic actin have resulted in conflicting data, and the presence and precise localization of filamentous actin (F-actin) in the synapses have still not been well clarified. We recently described a phalloidin based antifluorescein isothiocyanate system, which has been successfully developed for ultrastructural investigations of F-actin in the ependymal microvilli. By this technique, the present study has demonstrated the presence of F-actin in both the pre- and the postsynaptic regions in the synapses of spinal motoneurons. In the presynaptic terminal, F-actin was localized predominantly in the active zones and the adjacent synaptic vesicle clusters, including the vesicles docked at the active zones and a population of recycling vesicles. By contrast, the proximally located vesicle pool was much less intensely stained. In the postsynaptic region, F-actin was concentrated at the postsynaptic densities and stretched some way into the surrounding cytoplasm. Insofar as the axonal terminals analyzed in this study touched on either the cell body or the dendritic shaft, where the postsynaptic regions did not form spine-like specializations, our results cannot shed any light on the distribution of F-actin within spines. However, the present study has provided a hitherto unreported ultrastructural view of the subcellular distribution of F-actin in the synapse, which is thought to be helpful for understanding the roles of the synaptic actin cytoskeleton. PMID- 20575056 TI - Quantitative analysis of spinothalamic tract neurons in adult and developing mouse. AB - Understanding the development of nociceptive circuits is important for the proper treatment of pain and administration of anesthesia to prenatal, newborn, and infant organisms. The spinothalamic tract (STT) is an integral pathway in the transmission of nociceptive information to the brain, yet the stage of development when axons from cells in the spinal cord reach the thalamus is unknown. Therefore, the retrograde tracer Fluoro-Gold was used to characterize the STT at several stages of development in the mouse, a species in which the STT was previously unexamined. One-week-old, 2-day-old and embryonic-day-18 mice did not differ from adults in the number or distribution of retrogradely labeled STT neurons. Approximately 3,500 neurons were retrogradely labeled from one side of the thalamus in each age group. Eighty percent of the labeled cells were located on the side of the spinal cord contralateral to the injection site. Sixty-three percent of all labeled cells were located within the cervical cord, 18% in thoracic cord, and 19% in the lumbosacral spinal cord. Retrogradely labeled cells significantly increased in diameter over the first postnatal week. Arborizations and boutons within the ventrobasal complex of the thalamus were observed after the anterograde tracer biotinylated dextran amine was injected into the neonatal spinal cord. These data indicate that, whereas neurons of the STT continue to increase in size during the postnatal period, their axons reach the thalamus before birth and possess some of the morphological features required for functionality. PMID- 20575057 TI - Organization of amyloid-beta protein precursor intracellular domain-associated protein-1 in the rat brain. AB - Sustained activity-dependent synaptic modifications require protein synthesis. Although proteins can be synthesized locally in dendrites, long-term changes also require nuclear signaling. Amyloid-beta protein precursor intracellular domain associated protein-1 (AIDA-1), an abundant component of the biochemical postsynaptic density fraction, contains a nuclear localization sequence, making it a plausible candidate for synapse-to-nucleus signaling. We used immunohistochemistry to study the regional, cellular, and subcellular distribution of AIDA-1. Immunostaining was prominent in the hippocampus, cerebral cortex, and neostriatum. Along with diffuse staining of neuropil, fluorescence microscopy revealed immunostaining of excitatory synapses throughout the forebrain, and immunoreactive puncta within and directly outside the nucleus. Presynaptic staining was conspicuous in hippocampal mossy fibers. Electron microscopic analysis of material processed for postembedding immunogold revealed AIDA-1 label within postsynaptic densities in both hippocampus and cortex. Together with previous work, these data suggest that AIDA-1 serves as a direct signaling link between synapses and the nucleus in adult rat brain. PMID- 20575058 TI - Unmyelinated auditory type I spiral ganglion neurons in congenic Ly5.1 mice. AB - With the exception of humans, the somata of type I spiral ganglion neurons (SGNs) of most mammalian species are heavily myelinated. In an earlier study, we used Ly5.1 congenic mice as transplant recipients to investigate the role of hematopoietic stem cells in the adult mouse inner ear. An unanticipated finding was that a large percentage of the SGNs in this strain were unmyelinated. Further characterization of the auditory phenotype of young adult Ly5.1 mice in the present study revealed several unusual characteristics, including 1) large aggregates of unmyelinated SGNs in the apical and middle turns, 2) symmetrical junction-like contacts between the unmyelinated neurons, 3) abnormal expression patterns for CNPase and connexin 29 in the SGN clusters, 4) reduced SGN density in the basal cochlea without a corresponding loss of sensory hair cells, 5) significantly delayed auditory brainstem response (ABR) wave I latencies at low and middle frequencies compared with control mice with similar ABR threshold, and 6) elevated ABR thresholds and deceased wave I amplitudes at high frequencies. Taken together, these data suggest a defect in Schwann cells that leads to incomplete myelinization of SGNs during cochlear development. The Ly5.1 mouse strain appears to be the only rodent model so far identified with a high degree of the "human-like" feature of unmyelinated SGNs that aggregate into neural clusters. Thus, this strain may provide a suitable animal platform for modeling human auditory information processing such as synchronous neural activity and other auditory response properties. PMID- 20575060 TI - Lingual and palatal gustatory afferents each depend on both BDNF and NT-4, but the dependence is greater for lingual than palatal afferents. AB - Neurons of the geniculate ganglion innervate taste buds located in two spatially distinct targets, the tongue and palate. About 50% of these neurons die in Bdnf( /-) mice and Ntf4/5(-/-) mice. Bdnf(-/-)/Ntf4/5(-/-) double mutants lose 90-95% of geniculate ganglion neurons. To determine whether different subpopulations are differentially influenced by neurotrophins, we quantified neurons from two ganglion subpopulations separately and remaining taste buds at birth within each target field in wild-type, Bdnf(-/-), Ntf4/5(-/-), and Bdnf(-/-)/Ntf4/5(-/-) mice. In wild-type mice the same number of neurons innervated the anterior tongue and soft palate and each target contained the same number of taste buds. Compared to wild-type mice, Bdnf(-/-) mice showed a 50% reduction in geniculate neurons innervating the tongue and a 28% loss in neurons innervating the soft palate. Ntf4/5(-/-) mice lost 58% of the neurons innervating the tongue and 41% of the neurons innervating the soft palate. Taste bud loss was not as profound in the NT 4 null mice compared to BDNF-null mice. Tongues of Bdnf(-/-)/Ntf4/5(-/-) mice were innervated by 0 to 4 gustatory neurons and contained 3 to 16 taste buds at birth, indicating that some taste buds remain even when all innervation is lost. Thus, gustatory neurons are equally dependent on BDNF and NT-4 expression for survival, regardless of what peripheral target they innervate. However, taste buds are more sensitive to BDNF than NT-4 removal. PMID- 20575061 TI - Distribution of sex steroid hormone receptors in the brain of an African cichlid fish, Astatotilapia burtoni. AB - Sex steroid hormones released from the gonads play an important role in mediating social behavior across all vertebrates. Many effects of these gonadal hormones are mediated by nuclear steroid hormone receptors, which are crucial for integration in the brain of external (e.g., social) signals with internal physiological cues to produce an appropriate behavioral output. The African cichlid fish Astatotilapia burtoni presents an attractive model system for the study of how internal cues and external social signals are integrated in the brain as males display robust plasticity in the form of two distinct, yet reversible, behavioral and physiological phenotypes depending on the social environment. In order to better understand where sex steroid hormones act to regulate social behavior in this species, we have determined the distribution of the androgen receptor, estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA and protein throughout the telencephalon and diencephalon and some mesencephalic structures of A. burtoni. All steroid hormone receptors were found in key brain regions known to modulate social behavior in other vertebrates including the proposed teleost homologs of the mammalian amygdalar complex, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area. Overall, there is high concordance of mRNA and protein labeling. Our results significantly extend our understanding of sex steroid pathways in the cichlid brain and support the important role of nuclear sex steroid hormone receptors in modulating social behaviors in teleosts and across vertebrates. PMID- 20575059 TI - Molecular analysis of neocortical layer structure in the ferret. AB - Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. PMID- 20575062 TI - The effect of the physical states of binders on high-shear wet granulation and granule properties: a mechanistic approach toward understanding high-shear wet granulation process. Part II. Granulation and granule properties. AB - The objective is to provide mechanistic understanding of a preferred wet granulation process that a binder is added in a dry state. Blends of CaCO(3) and binders were prepared and used as model systems, and they were exposed to either 96% RH (rubbery/solution state) or 60% RH (glassy state) at room temperature to control the physical state of the binders, followed by high-shear granulation and particle size measurement. The blends of PVP K12, PVP K29/32, and HPC showed a significant increase in particle size after exposure to 96% RH. An increase of aspect ratio was also observed for the blend of HPC. In contrast, the blends being exposed to 60% RH did not exhibit any increase in particle size or aspect ratio. Regarding the effect of binder molecular weight on the mechanical strength of granules, granules of PVP K29/32 had higher strength than granules of PVP K12. This can be explained using polymer entanglement theory, in which the degree of polymerization (DP) of (N ~ 440-540) of PVP K29/32 is above the critical value (N(c) ~ 300-600) for entanglement; while DP of PVP K12 (N ~ 20-30) is below it. Finally, a water sorption-phase transition-diffusion induced granule growth model for granulation has been suggested. PMID- 20575063 TI - Acceptable levels of endotoxin in vaccine formulations during preclinical research. AB - This brief commentary reviews endotoxin levels of commercial vaccines and puts them into context for the preclinical researcher working in vaccines. Vaccines are not required to adhere to endotoxin levels as outlined in the United States Pharmacopoeia. Vaccine manufacturers have to show that the vaccine is safe and efficacious in clinical trials. Endotoxin limits are typically lot release specifications for most vaccines, but these values are not available to most researchers designing preclinical experiments. The limits outlined are calculated from endotoxin levels found in a variety of vaccine types such as gene vectors, recombinant subunits, polysaccharide, live attenuated, inactivated and toxoid vaccines. It is clear that certain families of vaccines such as toxoids contain much higher levels of endotoxin, where others such as purified recombinant subunits and gene vectors may contain very low levels. PMID- 20575064 TI - Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications: studies on curcumin and curcuminoides XLII. AB - Curcumin loaded alginate foams are proposed for application in antimicrobial photodynamic therapy of infected wounds. The drug loaded foams were formulated to provide a burst release of the photosensitizer when hydrated. The foams remained intact after hydration and would be possible to remove from the wound prior to irradiation without causing any tissue damage. The characterization of the prepared foams showed that both curcumin loaded and unloaded foams hydrated within 1 min and absorbed from 12 to 16 times their dry weight of a model physiological fluid. Curcumin, the model photosensitizer, has an extremely low solubility in water and may aggregate in aqueous environment. Cyclodextrins (CDs) and polyethylene glycol 400 (PEG 400) were therefore selected as solubilizers of curcumin in the foams to provide a burst release of the photosensitizer. Exposure to the prepared foams in combination with visible light irradiation (~9.7 J/cm(2)) resulted in >6 log reduction of Entrococcus faecalis cells. However, curcumin mediated photokilling of Escherichia coli was ineffective when CDs were selected as solubilizer of curcumin in the foams. An 81% reduction in viable E. coli cells was detected after treatment with the foam containing PEG 400 as the only solubilizer of curcumin combined with visible light irradiation (~29 J/cm(2)). PMID- 20575065 TI - The effect of the physical states of binders on high-shear wet granulation and granule properties: a mechanistic approach towards understanding high-shear wet granulation process. Part I. Physical characterization of binders. AB - In this study, the objective is to investigate the effect of the physical state of a binder on wet granulation and granule properties using a binary model system (CaCO(3)-binder), which is essential for understanding the mechanism of wet granulation when binder is added in a dry state. Part I focus on studying the phase behavior or the physical state change of four binders: PVP K12, K29/32, HPC, and HPMC, after exposure to either moisture or liquid water. Their interaction with water was studied by measuring the water sorption of binders and the binary blends of CaCO(3)-binder. Changes in the physical states of the binders at room temperature as a function of water content was monitored via dialysis experiments, and characterized by determining the glass transition temperatures (T(g)) of the binders with water. The results suggest that the PVP binders can absorb more water than the cellulosic binders which is same for binder alone and in the binary blends. PVP K12 undergoes a phase transition from the glassy state to the rubbery/solution state at much lower water content than PVP K29/32 (10% vs. 20%) at room temperature. The phase transition for HPC occurs with 10-15% water based on rheological measurements. PMID- 20575068 TI - Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons. AB - Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. We have examined the cellular and subcellular localization of Kv1.3 in the medial nucleus of the trapezoid body (MNTB) in the auditory brainstem, a nucleus in which neurons fire at high rates with high temporal precision. A clear gradient of Kv1.3 immunostaining along the lateral to medial tonotopic axis of the MNTB was detected. Highest levels were found in the lateral region of the MNTB, which corresponds to neurons that respond selectively to low-frequency auditory stimuli. Previous studies have demonstrated that MNTB neurons and their afferent inputs from the cochlear nucleus express three other members of the Kv1 family, Kv1.1, Kv1.2, and Kv1.6. Nevertheless, confocal microscopy of MNTB sections coimmunostained for Kv1.3 with these subunits revealed that the distribution of Kv1.3 differed significantly from other Kv1 family subunits. In particular, no axonal staining of Kv1.3 was detected, and most prominent labeling was in structures surrounding the somata of the principal neurons, suggesting specific localization to the large calyx of Held presynaptic endings that envelop the principal cells. The presence of Kv1.3 in presynaptic terminals was confirmed by coimmunolocalization with the synaptic markers synaptophysin, syntaxin, and synaptotagmin and by immunogold electron microscopy. Kv1.3 immunogold particles in the terminals were arrayed along the plasma membrane and on internal vesicular structures. To confirm these patterns of staining, we carried out immunolabeling on sections from Kv1.3(-/-) mice. No immunoreactivity could be detected in Kv1.3( /-) mice either at the light level or in immunogold experiments. The finding of a tonotopic gradient in presynaptic terminals suggests that Kv1.3 may regulate neurotransmitter release differentially in neurons that respond to different frequencies of sound. PMID- 20575069 TI - Characterization of the netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain. AB - In the adult rodent forebrain, astrocyte-like neural stem cells reside within the subventricular zone (SVZ) and give rise to progenitors and neuroblasts, which then undergo chain migration along the rostral migratory stream (RMS) to the olfactory bulb, where they mature into fully functional interneurons. Neurogenesis also occurs in the adult human SVZ, where neural precursors similar to the rodent astrocyte-like stem cell and neuroblast have been identified. A migratory pathway equivalent to the rodent RMS has also recently been described for the human forebrain. In the embryo, the guidance receptor neogenin and its ligands netrin-1 and RGMa regulate important neurogenic processes, including differentiation and migration. We show in this study that neogenin is expressed on neural stem cells (B cells), progenitor cells (C cells), and neuroblasts (A cells) in the adult mouse SVZ and RMS. We also show that netrin-1 and RGMa are ideally placed within the neurogenic niche to activate neogenin function. Moreover, we find that neogenin and RGMa are also present in the neurogenic regions of the human adult forebrain. We show that neogenin is localized to cells displaying stem cell (B cell)-like characteristics within the adult human SVZ and RMS and that RGMa is expressed by the same or a closely apposed cell population. This study supports the hypothesis that, as in the embryo, neogenin regulates fundamental signalling pathways important for neurogenesis in the adult mouse and human forebrain. PMID- 20575071 TI - Evidence regarding the integrity of the posterior medial lateral suprasylvian visual area in the cat. AB - Among the areas of lateral suprasylvian visual cortex in cats defined by Palmer et al. (J Comp Neurol [1978] 177:237-256), PMLS (posterior lateral suprasylvian area) has been the most studied. Although PMLS has strong and well-documented connections with area 17, it is unclear whether these connections extend to its upper visual field representation. We asked what cortical areas send input to the upper field representation in PMLS by making tracer injections in areas 17, 19, and posterior suprasylvian cortex. Tracer injections made in area 17's upper field representation in 15 cats failed to label the corresponding region in PMLS. Instead, they showed that area 17 is strongly connected with the posterior bank of the posterior suprasylvian sulcus (pSS), a region attributed by Palmer et al. to area 21a. Injections in area 19 had the same outcome. We consider this posterior upper field representation plus the lower field representation in PMLS to belong to a single area, LS (lateral suprasylvian visual area). Our data suggest that the upper field representation in PMLS belongs to a different area, most likely AMLS (anterior medial lateral suprasylvian area). PMID- 20575070 TI - Identification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain. AB - Previous studies showed that Tctex-1 immunoreactivity is selectively enriched in the germinal zones of adult brain. In this report we identify a regulatory region of the Tctex-1 gene that is capable of directing transgenic expression of green fluorescent protein (GFP) reporter that recapitulates the spatial and temporal expression pattern of endogenous Tctex-1. This construct specifically targeted expression to the nestin(+)/Pax6(+)/GLAST(+) radial glial cells and Tbr2(+) intermediate progenitors when the reporter construct was delivered to developing mouse neocortex via in utero electroporation. Characterization of mice transgenically expressing GFP under the same regulatory element showed that the GFP expression is faithful to endogenous Tctex-1 at the subgranular zone (SGZ) of dentate gyrus, ventricular/subventricular zone of lateral ventricles, and ependymal layer of 3rd ventricle of adult brains. Immunolocalization and bromodeoxyuridine incorporation studies of adult SGZ in four independent mouse lines showed that Tctex-1:GFP reporter selectively marks nestin(+)/GFAP(+)/Sox2(+) neural stem-like cells in two mouse lines (4 and 13). In two other mouse lines (17 and 18), Tctex-1:GFP is selectively expressed in Type-2 and Type-3 transient amplifying progenitors and a small subset of young neuronal progeny. The P/E-Tctex-1 reporter mouse studies independently confirmed the specific enrichment of Tctex-1 at adult SGZ stem/progenitor cells. Furthermore, these studies supported the notion that an analogous transcriptional program may be used to regulate neurogenesis in embryonic cerebral cortex and adult hippocampus. Finally, the genomic sequences and the reporter mouse lines described here provide useful experimental tools to advance adult neural stem cell research. PMID- 20575072 TI - Multiple neuropeptides in the Drosophila antennal lobe suggest complex modulatory circuits. AB - The fruitfly, Drosophila, is dependent on its olfactory sense in food search and reproduction. Processing of odorant information takes place in the antennal lobes, the primary olfactory center in the insect brain. Besides classical neurotransmitters, earlier studies have indicated the presence of a few neuropeptides in the olfactory system. In the present study we made an extensive analysis of the expression of neuropeptides in the Drosophila antennal lobes by direct profiling using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and immunocytochemistry. Neuropeptides from seven different precursor genes were unambiguously identified and their localization in neurons was subsequently revealed by immunocytochemistry. These were short neuropeptide F, tachykinin related peptide, allatostatin A, myoinhibitory peptide, SIFamide, IPNamide, and myosuppressin. The neuropeptides were expressed in subsets of olfactory sensory cells and different populations of local interneurons and extrinsic (centrifugal) neurons. In some neuron types neuropeptides were colocalized with classical neurotransmitters. Our findings suggest a huge complexity in peptidergic signaling in different circuits of the antennal lobe. PMID- 20575073 TI - Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single "cryptic" episode of focal hippocampal excitation in awake rats. AB - In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called "classic hippocampal sclerosis." No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive "endstage" pathology resulting from years of spontaneous seizures. We posed the alternative hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16-25 days postinjury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically "cryptic" excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID- 20575074 TI - Cellular and subcellular localization of the neuron-specific plasma membrane calcium ATPase PMCA1a in the rat brain. AB - Regulation of intracellular calcium is crucial both for proper neuronal function and survival. By coupling ATP hydrolysis with Ca(2+) extrusion from the cell, the plasma membrane calcium-dependent ATPases (PMCAs) play an essential role in controlling intracellular calcium levels in neurons. In contrast to PMCA2 and PMCA3, which are expressed in significant levels only in the brain and a few other tissues, PMCA1 is ubiquitously distributed, and is thus widely believed to play a "housekeeping" function in mammalian cells. Whereas the PMCA1b splice variant is predominant in most tissues, an alternative variant, PMCA1a, is the major form of PMCA1 in the adult brain. Here, we use immunohistochemistry to analyze the cellular and subcellular distribution of PMCA1a in the brain. We show that PMCA1a is not ubiquitously expressed, but rather is confined to neurons, where it concentrates in the plasma membrane of somata, dendrites, and spines. Thus, rather than serving a general housekeeping function, our data suggest that PMCA1a is a calcium pump specialized for neurons, where it may contribute to the modulation of somatic and dendritic Ca(2+) transients. PMID- 20575075 TI - Adsorption of monoclonal antibodies to glass microparticles. AB - Microparticulate glass represents a potential contamination to protein formulations that may occur as a result of processing conditions or glass types. The effect of added microparticulate glass to formulations of three humanized antibodies was tested. Under the three formulation conditions tested, all three antibodies adsorbed irreversibly at near monolayer surface coverages to the glass microparticles. Analysis of the secondary structure of the adsorbed antibodies by infrared spectroscopy reveal only minor perturbations as a result of adsorption. Likewise, front-face fluorescence quenching measurements reflected minimal tertiary structural changes upon adsorption. In contrast to the minimal effects on protein structure, adsorption of protein to suspensions of glass microparticles induced significant colloidal destabilization and flocculation of the suspension. PMID- 20575076 TI - Predicting and monitoring cancer treatment response with diffusion-weighted MRI. AB - An imaging biomarker that would provide for an early quantitative metric of clinical treatment response in cancer patients would provide for a paradigm shift in cancer care. Currently, nonimage based clinical outcome metrics include morphology, clinical, and laboratory parameters, however, these are obtained relatively late following treatment. Diffusion-weighted MRI (DW-MRI) holds promise for use as a cancer treatment response biomarker as it is sensitive to macromolecular and microstructural changes which can occur at the cellular level earlier than anatomical changes during therapy. Studies have shown that successful treatment of many tumor types can be detected using DW-MRI as an early increase in the apparent diffusion coefficient (ADC) values. Additionally, low pretreatment ADC values of various tumors are often predictive of better outcome. These capabilities, once validated, could provide for an important opportunity to individualize therapy thereby minimizing unnecessary systemic toxicity associated with ineffective therapies with the additional advantage of improving overall patient health care and associated costs. In this report, we provide a brief technical overview of DW-MRI acquisition protocols, quantitative image analysis approaches and review studies which have implemented DW-MRI for the purpose of early prediction of cancer treatment response. PMID- 20575078 TI - Adipose tissue distribution in children: automated quantification using water and fat MRI. AB - PURPOSE: To develop and validate a method for rapid acquisition and automated processing of magnetic resonance (MR) images for analysis of abdominal adipose tissue distribution in children. MATERIALS AND METHODS: The study included 21 (10 girls, 11 boys) healthy 5-year-old children. Rapid water and fat MR imaging (6 sec) was performed using a 2-point-Dixon technique on a 1.5T MR scanner using an 8-channel cardiac coil. An automated image processing algorithm was developed for automated segmentation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), respectively. The results from the fully automated analysis were compared to those from a semiautomated analysis, performed by three operators, from the same images. RESULTS: The automated analysis was seen to give results with strong correlation to the reference measurements (r >or= 0.997); however, the SAT volume was underestimated by 9.4 +/- 3.8%. The accuracy of the automated segmentation of VAT and SAT (TP: true positive, FP: false positive, mean +/- SD, %) was TP: 83.6 +/- 8.5, FP: 12.7 +/- 6.8; and TP: 89.9 +/- 3.6, FP: 0.7 +/- 0.3, respectively. CONCLUSION: A method for rapid imaging and fully automated postprocessing of abdominal adipose tissue distribution is presented. The method allows robust and time-efficient measurement of adipose tissue distribution in young children. PMID- 20575077 TI - Freehand MRI-guided preoperative needle localization of breast lesions after MRI guided vacuum-assisted core needle biopsy without marker placement. AB - PURPOSE: To evaluate the feasibility of magnetic resonance imaging (MRI)-guided preoperative needle localization (PNL) of breast lesions previously sampled by MRI-guided vacuum-assisted core needle biopsy (VACNB) without marker placement. MATERIALS AND METHODS: We reviewed 15 women with 16 breast lesions undergoing MRI guided VACNB without marker placement who subsequently underwent MRI-guided PNL, both on an open 0.5T magnet using freehand techniques. Mammograms and specimen radiographs were rated for lesion visibility; MRI images were rated for lesion visibility and hematoma formation. Imaging findings were correlated with pathology. RESULTS: The average prebiopsy lesion size was 16 mm (range 4-50 mm) with 13/16 lesions located in mammographically dense breasts. Eight hematomas formed during VACNB (average size 13 mm, range 8-19 mm). PNL was performed for VACNB pathologies of cancer (5), high-risk lesions (5), or benign but discordant findings (6) at 2-78 days following VACNB. PNL targeted the lesion (2), hematoma (4), or surrounding breast architecture (10). Wire placement was successful in all 16 lesions. Final pathology showed six cancers, five high-risk lesions, and five benign findings. CONCLUSION: MRI-guided PNL is successful in removing lesions that have previously undergone VACNB without marker placement by targeting the residual lesion, hematoma, or surrounding breast architecture, even in mammographically dense breasts. PMID- 20575079 TI - Dynamic visualization of arachnoid adhesions in a patient with idiopathic syringomyelia using high-resolution cine magnetic resonance imaging at 3T. AB - A 39-year-old female patient with thoracic syringomyelia underwent routine magnetic resonance imaging (MRI) and 3 T MRI to investigate the value of retrospectively cardiac-gated cine steady-state free precession (SSFP) MRI in the preoperative and postoperative diagnosis of arachnoid membranes in the spinal subarachnoid space. Therefore, 3T MRI included sagittal and transverse retrospectively cardiac-gated cine balanced fast-field echo (balanced-FFE) sequences both preoperatively and after microsurgical lysis of arachnoid adhesions and expansive duraplasty. Arachnoid membranes were detected and this result was correlated with intraoperative findings and the results of routine cardiac-gated phase-contrast cerebrospinal fluid (CSF) flow MRI. Retrospectively cardiac-gated cine SSFP MRI enabled imaging of arachnoid membranes with high spatial resolution and sufficient contrast to delineate them from hyperintense CSF preoperatively and postoperatively. The images were largely unaffected by artifacts. Surgery confirmed the presence of arachnoid adhesions in the upper thoracic spine. Not all arachnoid membranes that were seen on cine balanced-FFE sequences caused significant spinal CSF flow blockages in cardiac-gated phase contrast CSF flow studies. In conclusion, retrospectively cardiac-gated cine SSFP MRI may become a valuable tool for the preoperative detection of arachnoid adhesions and the postoperative evaluation of microsurgical adhesiolysis in patients with idiopathic syringomyelia. PMID- 20575080 TI - Reducing the impact of white matter lesions on automated measures of brain gray and white matter volumes. AB - PURPOSE: To develop an automated lesion-filling technique (LEAP; LEsion Automated Preprocessing) that would reduce lesion-associated brain tissue segmentation bias (which is known to affect automated brain gray [GM] and white matter [WM] tissue segmentations in people who have multiple sclerosis), and a WM lesion simulation tool with which to test it. MATERIALS AND METHODS: Simulated lesions with differing volumes and signal intensities were added to volumetric brain images from three healthy subjects and then automatically filled with values approximating normal WM. We tested the effects of simulated lesions and lesion filling correction with LEAP on SPM-derived tissue volume estimates. RESULTS: GM and WM tissue volume estimates were affected by the presence of WM lesions. With simulated lesion volumes of 15 mL at 70% of normal WM intensity, the effect was to increase GM fractional (relative to intracranial) volumes by approximately 2.3%, and reduce WM fractions by approximately 3.6%. Lesion filling reduced these errors to approximately 0.1%. CONCLUSION: The effect of WM lesions on automated GM and WM volume measures may be considerable and thereby obscure real disease mediated volume changes. Lesion filling with values approximating normal WM enables more accurate GM and WM volume measures and should be applicable to structural scans independently of the software used for the segmentation. PMID- 20575081 TI - DNA damage in brain cells and behavioral deficits in mice after treatment with high doses of amantadine. AB - Amantadine (AMA) is an uncompetitive antagonist of the N-methyl-d-aspartate receptor, with clinical application, acting on treatment of influenza A virus and Parkinson's disease. It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic/mutagenic activities. Adult male CF-1 mice were treated with a systemic injection of AMA (15, 30 or 60 mg kg(-1) ) 20 min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60 mg kg(-1) AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3-day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity. PMID- 20575082 TI - Statin use and depressive symptoms in a prospective study of community-living older persons. AB - PURPOSE: The association between statin use and depression is complex, and research findings have been mixed. The present study aimed to investigate the association of statin use with depressive symptoms among community-living older persons, and its effect modifications by gender and medical co-morbidity. METHOD: Prospective observational study of 1803 participants aged 55 and above in the Singapore Longitudinal Ageing Studies cohort, with data of statin use and other risk factors for depression at baseline, and Geriatric Depression Scale (GDS) symptom scores at follow-up (1.5 years). RESULTS: Controlling for baseline demographics, cholesterol level and medical co-morbidities, statin use was not associated with depressive symptom scores in the whole sample overall (regression coefficient = -0.12 (SE 0.10), F([1,1782]) = 1.44, p = 0.23). Post hoc analyses suggested that statin use may be associated with fewer depressive symptoms in women (p = 0.02), and more depressive symptoms in men, particularly those with more medical co-morbidities (p = 0.04) and multiple drug use (p = 0.02). CONCLUSION: This study provided no strong evidence that support an overall association of statin use and depressive symptoms. The post hoc findings in this study are suggestive but may also be spurious and should be replicated in other studies. PMID- 20575083 TI - In vitro derivation of germ cells from embryonic stem cells in mammals. AB - Previous reports have shown that embryonic stem (ES) cells, derived from the inner cell mass of mouse or human blastocysts, could differentiate in vitro into female and male germ cells as well as into the cell types of all three germ layers. While in one case, the ES cell-derived germ cells have been reported to give birth to live offspring in the mouse, these cells differ in fertilization capacity from the sperm and oocytes produced in vivo as they cannot complete meiosis under in vitro conditions. The efficiency of functional germ cell isolation from ES cells is also low. According to published reports, factors such as the proper selection of feeder cells, including ovarian granulosa cells and those which could secrete bone morphogenic protein-4 (BMP4), and the addition of retinoic acid into culture medium, could to some extent establish and improve the microenvironment ES cells rely on for differentiation into germ cells. This review briefly describes the progress of deriving germ cells from ES cells and discusses possible factors that could improve in vitro gamete production. PMID- 20575084 TI - Effect of maternal age on the developmental competence and progression of nuclear maturation in bovine oocytes. AB - Progression of meiotic division in oocytes and early embryonic development are affected by oocytes quality. In most mammals, oocyte quality declines with increase in maternal age. The main aim of the present study is to investigate the effect of maternal age on developmental competence, progression of meiotic division, and associated kinetics of maturation promoting factor (MPF) activity in bovine oocytes. Oocytes were collected from the ovaries of young and old cows (here after referred to as young cow oocytes and old cow oocytes, respectively). When old cow oocytes were matured and fertilized in vitro, the rate of abnormal fertilization was greater than that in young cow oocytes. Moreover, progression of nuclear maturation and activation of MPF during oocyte maturation (or inactivation of MPF and formation of pronucleus after insemination) were faster in old cow oocytes than in young cow oocytes. Relative expression of cyclin B, cyclin-dependent kinase 1 and MAD2 transcripts in either immature or mature oocytes did not differ between the two groups. When cumulus cells (CC) were removed and denuded oocytes were cultured, there was no difference in the progression of nuclear maturation between the two age groups. Moreover gap junctions between oocytes and CC disappeared more rapidly during maturation of old cow oocytes than of young cow oocytes. These results suggest that the fertilization ability of old cow oocytes is low and that premature progression of meiotic division in these oocytes is partly due to impaired oocyte-CC gap junctions communication. PMID- 20575085 TI - Synchronous behaviors of CBP and acetylations of lysine 18 and lysine 23 on histone H3 during porcine oocyte first meiotic division. AB - As a transcriptional coactivator and acetyltransferase, CREB-binding protein (CBP) is widely characterized due to its functions in cell proliferation and development. However, the activities of CBP in oocyte meiosis are not completely clear. Here we showed that the localization and expression of CBP changed regularly with the progression of porcine oocyte meiosis. The emergence of CBP in chromosomal domains is temporally coincident with the establishments of acetylated lysine 18 (AcH3/K18), lysine 23 (AcH3/K23) and dimethylated arginine 17 (dime-H3/R17) of histone H3 at meiotic stages from germinal vesicle breakdown (GVBD) to metaphase I (MI). Both CBP expression and these three histone modifications persisted to telophase I (TI). When trichostatin A (TSA) was used to enhance histone acetylations in porcine oocytes, we found that hyperacetylations of H3K18 and H3K23 occurred at meiotic stage from GVBD to TI, together with advanced and enhanced expression of CBP in the nucleus. In addition, disturbance of CBP activity by treatment with 2-Naphthol-AS-Ephosphate (KG-501, a drug targeting the KIX domain of CBP that disrupts the formation of CBP functional complex) led to synchronous decreases of CBP expression, AcH3/K18 and AcH3/K23 in chromosomal domains during oocyte meiosis. Therefore, these results indicate that the synchronous changes of CBP expression, AcH3/K18 and AcH3/K23 occur during porcine oocyte meiosis. PMID- 20575086 TI - Resolution of extensive severe bronchiectasis in an infant. AB - Bronchiectasis is, by definition, an irreversible condition. Following recent reports of reversible bronchiectasis in children, it has been suggested that the definition be broadened to include pre-bronchiectasis and transitional reversible states. We describe the case of a young infant who had extensive, severe bronchiectasis of unknown etiology that resolved following prolonged treatment with antibiotics and a tapering course of oral steroids. We suggest that the prolonged treatment may have played a role, perhaps by eradicating infection and thus enabling regeneration of bronchial anatomy. PMID- 20575087 TI - Pressure-rate product and phase angle as measures of acute inspiratory upper airway obstruction in rhesus monkeys. AB - RATIONALE: There are limited validated, objective, and minimally invasive techniques for the bedside evaluation of upper airway obstruction (UAO) in sick infants, despite its frequency in pediatric medicine. Prior techniques include pressure-rate product (PRP), a product of esophageal pressure and respiratory rate and phase angles (PAs), a measure of asynchrony between ribcage and abdominal respiratory movements in infants with UAO. The purpose of this study is to validate the PRP and compare it to a previously validated PA in rhesus monkeys. METHODS: Calibrated resistors were applied to the inspiratory limb of 10 anesthetized, intubated, and spontaneously breathing rhesus monkeys (weight 8.7 +/- 2.5 kg). Airway pressure, respiratory rate, PAs, heart rate, and oxygen saturation were recorded. Obstruction was applied in random order as 0, 5, 20, 200, 500, and 1,000 cmH(2)O/L/sec for 2-min periods, the last 15 sec (10-20 breaths) were analyzed for each timeframe. RESULTS: PA increased significantly at the 200 cmH(2)O/L/sec level but it reached a plateau above 500 cmH(2)O/L/sec. PRP rose progressively and was significantly different at all levels of obstruction. Esophageal pressure change was progressively and statistically significantly different from baseline and each other at 200, 500, and 1,000 cmH(2)O/L/sec (P < 0.001). CONCLUSIONS: In this model of UAO, PRP tracks increasing inspiratory load better than PA. PRP continued to be linear up through the highest inspiratory resistance where the change in PA reached a plateau before the highest load. The assessment of esophageal pressure changes may offer the simplest objective measure of UAO. PMID- 20575088 TI - Children with corrected or palliated congenital heart disease on home mechanical ventilation. AB - Infants and children with surgically corrected or palliated congenital heart disease (CHD) are at risk for chronic respiratory failure, necessitating home mechanical ventilation (HMV) via tracheostomy. However, very little data exists on this population or their outcomes. We conducted a retrospective chart review of all children with CHD enrolled in the Childrens Hospital Los Angeles HMV program between 1994 and 2009. Data were collected on type of heart lesion, surgeries performed, number of failed extubations, timing of tracheostomy, mortality, length of time on HMV, weaning status, associated co-morbidities, and Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) category. Thirty-five children were identified; six with single ventricle anatomy, who received palliative procedures. Twenty-three (66%) patients are alive; 8 (23%) living patients have been weaned off HMV. Twelve (34%) patients are deceased. The incidence of mortality for single ventricle patients was 50%, and only one of the surviving children has received final palliation and weaned off HMV. Eight of nine patients (89%) with a RACHS score > or =4 died, and none have been weaned off of HMV. The 5-year survival for all CHD HMV patients was 68%; 90% for patients with RACHS < or =3; and 12% for patients with score > or =4. Children with more complex lesions, as demonstrated by single ventricle physiology or greater RACHS scores, had higher mortality rates and less success weaning off HMV. This case series suggests that caregivers should give serious consideration to the type of heart defect as they advise families considering HMV in children with CHD. PMID- 20575089 TI - Pseudomonas aeruginosa in children with cystic fibrosis diagnosed through newborn screening: assessment of clinic exposures and microbial genotypes. AB - BACKGROUND: Chronic pulmonary infection with Pseudomonas aeruginosa (PA) is responsible for significant morbidity and mortality in cystic fibrosis (CF). Because of the limited studies evaluating early exposure and the progression of genetic variability of PA, our goal was to assess PA in young children with CF followed in two clinic types. METHODS: A total of 39 infants with CF diagnosed through newborn screening were randomly assigned to either a segregated (PA-free) or mixed (PA-positive) clinic at two different CF centers, one of which replaced an older, mixed clinic where nosocomial acquisition was suspected. Oropharyngeal (OP) swab cultures were examined with subsequent genotyping to characterize the strains of PA isolated. RESULTS: We found that 13/21 segregated clinic patients and 14/18 mixed clinic patients showed positive PA, with median acquisition ages of 3.3 and 2.2 years, respectively (P = 0.57). The median time to PA acquisition, however, was significantly longer in the new clinic with proper hygiene precautions compared to an old site (5.0 years vs. 1.7 years, P < 0.001). The majority of subjects isolated a single genotype of PA or AP-PCR types during the study period with eight subjects clearing the isolate after only one positive culture. The development of chronic colonization yielded the predominance of a single major genotype or AP-PCR type. CONCLUSIONS: Segregation of infants and young children with CF in PA-negative or PA-positive clinics did not alter the time to first PA isolation in this randomized assessment of facilities with hygienic precautions. During the early infection period where PA is first isolated in young children with CF, patients cleared different PA strains until a predominant strain established permanent colonization. PMID- 20575090 TI - Intracellular bimodal nanoparticles based on quantum dots for high-field MRI at 21.1 T. AB - Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. PMID- 20575091 TI - Balloon dilatation in management of postoperative airway obstruction due to tracheal bronchus associated with right main bronchial stenosis: emphasizing the role of three-dimensional computed tomography on preoperative evaluation. AB - Three-dimensional computed tomography (3D-CT) not only allows accurate preoperative delineation of the lesions but also provides precise pathomechanic diagnosis for planning the most effective treatment to avoid respiratory compromise. In a 10-month-old baby girl, who was ventilator-dependent after successful correction of double outlet right ventricle (DORV), flexible fiberoptic bronchoscopy (FFB) revealed the new formation of postoperative airway obstruction over the right main bronchus (RMB) and obstructed right tracheal bronchus (RTB). 3D-CT demonstrated tracheobronchial obstruction (TBO) was caused by the dilated ascending aorta (AAo) and right pulmonary artery (RPA). Sequential treatments including artery pexy of AAo and RPA and balloon dilatation (BD) of the stenotic RTB and RMB had successfully restored the airway patency. The patient was successfully weaned from ventilator 2 days after treatments and has shown no respiratory difficulty thus far. Thus, the impact of preoperative 3D-CT on planning treatment cannot be emphasized. PMID- 20575092 TI - Community-acquired Moraxella catarrhalis pneumonia in previously healthy children. AB - BACKGROUND: The aim of this study was to determine if Moraxella catarrhalis is a common cause of community acquired pneumonia in children with no chronic medical problems. A secondary goal was to describe the clinical features of children with M. catarrhalis pneumonia. METHODS: A systematic literature search was conducted for (i) case series of pediatric community-acquired pneumonia (CAP) where one or more diagnostic tests for M. catarrhalis were applied to all cases and (ii) case reports of previously healthy children with proven M. catarrhalis pneumonia. RESULTS: There were nine case series describing a total of 1,500 children with CAP. The number of children tested and yield was as follows: blood cultures 0/402 (0%); sputum cultures 15/157 (10%); nasopharyngeal, or postnasal cultures 129/521 (25%); sputum or nasopharyngeal cultures 0/74 (0%) (one study allowed either); nucleic acid amplification testing 2/100 (2%); serology 30/976 (3%). There were eight case reports of CAP with M. catarrhalis in previously well children. Children were ages 3 weeks to 7 years of age (median 14 months). Six of 8 (75%) children required mechanical ventilation. All survived. CONCLUSION: It is common to detect M. catarrhalis in upper respiratory secretions in children with pneumonia, but bacteremia or seroconversion is rare. There are only eight well documented case reports CAP due to M. catarrhalis in previously well children, with there being no distinctive features in the eight cases described to date. This organism is likely a rare cause of CAP in previously healthy children. PMID- 20575093 TI - An unusual cause of fever in a neonate: influenza A (H1N1) virus pneumonia. AB - The 2009 flu outbreak in humans, known as H1N1 influenza A, refers to influenza A due to a new H1N1 strain called swine-origin influenza virus A. The signs and symptoms of novel influenza A (H1N1) virus infection are similar to those of seasonal influenza, and specific diagnostic testing is required to distinguish novel influenza A (H1N1) virus from seasonal influenza virus. It results in various degrees of infection, ranging from mild to severe to fatal. For the treatment of swine-origin influenza virus A oseltamivir and zanamivir are effective in most cases. Influenza A (H1N1) pneumonia in the newborn has not been yet reported in the literature. To our knowledge, this is the first report of a neonate of pneumonia in which influenza A (H1N1) virus was isolated. PMID- 20575094 TI - Skeletal dysplasias: evaluation with impulse oscillometry and thoracoabdominal motion analysis. AB - BACKGROUND: Children with skeletal dysplasia (SD) often have pulmonary disease, which can be life threatening. In clinical practice, chest wall and formal respiratory function tests are difficult to perform owing to the small size and cooperation. The objective of this study was to demonstrate distinct thoracopulmonary function patterns in children with SD. METHODS: We conducted a retrospective study reviewing pulmonary function tests from 17 patients with the diagnosis of SD. Three subgroups were studied: Morquio syndrome (MS), metatropic spondylocostal dysplasia (MSD), and unspecified skeletal dysplasias (SDU). Rib cage contribution to tidal volume excursions (%RC), phase angle (Phtheta), phase relation during total breath (PhRTB), respiratory resistance (Rrs(5-35) Hz), respiratory reactance (Xrs(5-35) Hz), resonant frequency, and their frequency dependency were analyzed. Values were age-matched and height-matched to reference values of healthy subjects. RESULTS: There was a decrease in %RC and an increase in PhRTB (P < 0.05) in the SD group. %RC differed between subgroups [MS: 46.4 +/- 1.8% SE, MSD: 18.4 +/- 2.6% SE, SDU: 27.5 +/- 5.2% SE (P < 0.05)]; Phtheta was within reference values only in MS, which exhibited a decrease in Xrs at 5 Hz (P < 0.05) and an increase in Rrs independent of the frequency. SDU showed a decrease in Xrs at 35 Hz (P < 0.05), no differences were found in Rrs. In MS, a correlation was found between RC and Rrs at all frequencies (r = -0.98, P < 0.01) and between Xrs(5-10) and Phtheta (r = -0.93, P < 0.05). CONCLUSIONS: Thoracoabdominal dysfunction was associated with altered chest wall reactance at high frequencies in a subgroup of SD patients with abnormal lung reactance and central airway involvement in MS. PMID- 20575095 TI - Voriconazole inhibition of vitamin A metabolism: are adverse events increased in cystic fibrosis patients? AB - BACKGROUND: As Voriconazole is being used more frequently in cystic fibrosis (CF) patients, we aimed to describe the adverse events associated with voriconazole treatment in this population. METHODS: We performed a retrospective cohort study of all children with CF who received voriconazole between September 2006 and August 2008. RESULTS: Five of six CF patients receiving treatment developed photosensitivity, whereas all six patients reported visual disturbances. We report two clinical cases of particular interest: a 7-year-old boy developed striking erythema in the face and upper thorax; a 16-year-old girl who reported unexpected visual disturbances, including scotomas and tunneling vision. CONCLUSION: Significant adverse effects of voriconazole were noted in all treated CF patients. We speculate that this may be due to suppression of activity of hepatic enzymes involved in all transretinonic acid metabolism coupled with vitamin A supplementation in CF. Consideration should be given to reducing vitamin A supplementation during voriconazole treatment. PMID- 20575096 TI - "Atypical steroid response" in a pulmonary inflammatory myofibroblastic tumor. AB - A 6-year-old girl was evaluated for the presence of a paratracheal mass with right upper lobe atelectasis due to an endobronchial mass. Bronchoscopic biopsy established a diagnosis of inflammatory myofibroblastic tumor (IMT) and prednisone initially led to a significant reduction of the endobronchial lesion. However, 8 weeks later, when still on prednisone, the mediastinal mass enlarged dramatically. At thoracotomy, a well-circumscribed, multilobulated mass was partially resected and a diagnosis of IMT confirmed. Immunosuppression by corticosteroids may have favored the rapid progression of this apparently benign, indolent tumor. PMID- 20575097 TI - Diffuse chondroid malformation of the lung: cases series of a hitherto undescribed congenital lung disease. AB - Congenital chondroid lesions of the lung are rare pathological findings. They are a constant feature of lung malformations such as giant cystic pulmonary chondroid hamartoma, chondroid cystic malformation, and in the "cartilaginous variant" of congenital adenomatoid malformation. All of these present as a large single thoracic mass.We present the cases of three males and two females with hitherto undescribed diffuse chondroid lung disease, all but one of whom had neonatal respiratory distress syndrome with interstitial syndrome on chest radiograph. The pathological findings were similar in all patients, showing large areas of disorganized lung parenchyma containing diffusely distributed mature cartilage islands. With a mean follow-up of 6 years, all patients had a favorable outcome. This diffuse chondroid lung disease appears to be a new entity whose initial presentation mimicked interstitial lung disease without the usual clinical, radiological, and histological features. We speculate that it could be part of a clinical spectrum between malformative chondroid lung cyst and congenital pulmonary airway malformation. PMID- 20575098 TI - CMV pneumonia in HIV-infected ventilated infants. AB - BACKGROUND: The contributing role of cytomegalovirus (CMV) in infants treated for Pneumocystis jiroveci pneumonia (PJP) is unknown. High dose steroids used in the treatment of PJP may further immunocompromise these infants contributing to the development of CMV pneumonia. AIM: The aim of this study was to determine the role of CMV pneumonia in infants being ventilated for suspected PJP. METHODS: In this prospective study HIV infected infants being treated with trimethoprim sulfamethoxazole (TMP/SMX) and ventilated for suspected PJP were included if they had not responded to treatment. Open lung biopsy was performed if there was no improvement in ventilatory requirements. RESULTS: Twenty-five HIV positive infants with a mean age of 3.3 months were included. Lung biopsy was performed in 17 (68%) and post-mortem lung tissue was obtained in 8 (32%). After evaluation of the histology, immunohistochemistry, and viral cultures from lung tissue, the most likely causes of pneumonia were: CMV and PJP dual infection 36% (n = 9), CMV pneumonia 36% (n = 9), and PJP 24% (n = 6). The pp65 test for CMV antigen was falsely negative in 24%. The mean blood CD4 count was 287/microl. There was an association between the CD4 lymphocyte status and the final diagnosis, with the CMV and PJP group (CD4 110/microl) having the lowest CD4 status (P = 0.0128). Pediatric Intensive Care Unit (PICU) mortality was 72% (n = 18) and in hospital mortality 88%. CONCLUSION: Of the ventilated infants failing to respond to treatment, 72% had histologically confirmed CMV pneumonia, probably accounting for the high mortality in this cohort. The incidence of CMV disease in HIV infected infants being ventilated for severe pneumonia warrants that ganciclovir is used empirically until CMV disease is excluded. The role of lung biopsy in these circumstances needs to be researched. PMID- 20575099 TI - Toll-like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics. AB - The respiratory syncytial virus (RSV) antigen serves as ligand for Toll-like receptor (TLR) 4 that is a transmembrane signaling receptor in macrophages and dendritic cells. According to current evidence single nucleotide polymorphism involving amino acid 299 influences the susceptibility to severe RSV infections. The Asp299Gly allele has been shown to influence the TLR4-mediated signaling causing conformational change in the extracellular domain that recognizes pathogen-associated molecular patterns. The aim was to study the association between the TLR4 Asp299Gly polymorphism and the susceptibility to severe RSV bronchiolitis in infants. Altogether 312 cases and 356 controls, selected on the basis place of residence, date of birth, gender, and gestation at birth, were studied. When adjusted for multiple dependent variables, no allele or genotype frequency difference was found between the cases and the controls. Post hoc analysis revealed that during the year 2000 epidemics, the Gly299Gly genotype associated with protection against severe RSV and during 2004 epidemics Gly299Gly genotype and 299Gly allele associated with severe RSV. To conclude, we could not confirm the association of the Gly299 allele with severe RSV. This is consistent with the evidence that the susceptibility to severe RSV infection is principally dependent on environmental and constitutional factors. We propose that the risk of severe RSV infection may additionally depend on the interaction between individual TLR4 genotype and the particular RSV group causing bronchiolitis. PMID- 20575100 TI - Adiposity and low-grade systemic inflammation modulate matrix metalloproteinase-9 levels in Greek children with sleep apnea. AB - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children. METHODS: Consecutive children with snoring who underwent polysomnography and were found to have OSA (obstructive apnea-hypopnea index-OAHI > or = 1 episode/hr) were recruited. Subjects without OSA (OAHI < 1 episode/hr) were included for comparison. Morning plasma MMP-9 and CRP were measured. RESULTS: Twenty-nine children with moderate-to-severe OSA (age 5.4 +/- 1.5 years; OAHI 13.9 +/- 13.0 episodes/hr), 55 participants with mild OSA (6.4 +/- 2.6 years; OAHI 2.4 +/- 1.1 episodes/hr) and 22 subjects without OSA (6.8 +/- 2.6 years; OAHI 0.6 +/- 0.2 episodes/hr) were studied. Children with moderate-to-severe OSA were similar to those with mild OSA or without OSA regarding ln-transformed MMP-9 values (5.87 +/ 0.60 vs. 5.84 +/- 0.55 vs. 5.80 +/- 0.46; P > 0.05) and CRP concentrations (0.22 +/- 0.29 mg/dl vs. 0.21 +/- 0.36 vs. 0.13 +/- 0.16 mg/dl; P > 0.05). In multiple linear regression, body mass index (P = 0.027) and CRP levels (P = 0.008), but not OAHI or SpO(2) nadir (P > 0.05), were significantly related to MMP-9 values. CONCLUSIONS: Adiposity and systemic inflammation unrelated to OSA severity, modulate MMP-9 levels in Greek children. PMID- 20575101 TI - Assessment and validation of bronchodilation using the interrupter technique in preschool children. AB - OBJECTIVE: To determine and validate a cut-off value for bronchodilation using the interrupter resistance (Rint) in preschool children. PATIENTS AND METHODS: Rint was measured in 60 healthy children (age range 2.7-6.4 years) before and after salbutamol inhalation (200 microg). Four potential methods for assessing BDR were evaluated: percent change from baseline, percent change of predicted values, absolute change in Rint, and change in Z-score. These cut-off values, determined as the fifth percentile of the healthy group, were applied to children referred for the assessment of recurrent wheezing, classified on the basis of acute symptoms and/or abnormal chest examination into symptomatic (n = 60, age range 2.9-6.1 years) and asymptomatic (n = 60, age range 2.5-5.7 years) groups. RESULTS: The cut-off values for bronchodilation calculated in healthy children were: -32% baseline; -33% predicted; -0.26 kPa L(-1) sec; and -1.25 Z-scores. Assessing BDR in children with a history of wheezing by either a decrease in absolute Rint or a decrease in Z-score gave sensitivity, specificity, negative predictive value, and positive predictive value all >80% for detecting children with current respiratory symptoms. CONCLUSIONS: Both a decrease in Rint > or =0.26 kPa L(-1) sec and a decrease in Z-score of > or =1.25 are appropriate for assessing BDR in preschool children with a history of recurrent wheezing. As Z score is a more general solution, we recommend using a change in Z-score to determine BDR in preschool children. Further longitudinal studies will be required to determine the clinical utility of measuring BDR in managing lung disease in such children. PMID- 20575102 TI - Pulmonary hypertension secondary to partial pulmonary venous obstruction in a child with Cantu syndrome. AB - We report on an African-American male with Cantu syndrome who required a pericardial window for a significant pericardial effusion in infancy and was subsequently found to have partial pulmonary venous obstruction (PVO) leading to pulmonary hypertension. Measurement of bilateral pulmonary capillary wedge pressures is important to uncover partial PVO. PMID- 20575103 TI - Current status of Oriental medicine in treating Korean allergy patients. AB - PURPOSE: To evaluate the prevalence, compliance, pattern of use, and economic cost of OM in Korean allergy patients. METHODS: A total of 647 allergy patients were enrolled from 10 general hospitals, and were surveyed by the questionnaire. It consisted of 12 items and regarded the prescription rates, reasons for referring, their opinions for the efficacy of OM, and economic costs. RESULTS: A total of 259 (40.5%) patients had used OM, and 35.5% of these patients experienced two or more kinds of these practices. A patients' income or education level did not affect the prescription rates of OM. Of the patients that used OM, 34.6% of them were satisfied with the effect of OM treatment, and 40.9% of them were inclined to continue with their OM treatments. The most frequent reasons for choosing OM were the patient's belief that OM can predispose 'allergic constitution to normal' (30.2%), worries about the possible adverse reactions of the long-term administration of the proven drugs (20.2%), and the safety of OM (15.6%). However, 18.9% of these patients experienced perceived adverse events to their OM treatment such as skin rashes, gastrointestinal discomfort, and hepatitis. The patients that have used OM spent on average $915 US dollars annually for OM treatment. CONCLUSIONS: Many Korean allergy patients are cliental to OM. Some patients experienced a satisfactory treatment effect from OM, however, others had no treatment effect, even adverse event. Therefore, it is important to educate people to use OM appropriately to make harmony with modern medicine. PMID- 20575104 TI - FT-IR spectroscopy in diagnosis of diabetes in rat animal model. AB - In recent years, Fourier Transform Infrared (FT-IR) spectroscopy has had an increasingly important role in the field of pathology and diagnosis of disease states. In the current study, FT-IR spectroscopy together with cluster analysis were used as a diagnostic tool in the discrimination of diabetic samples from control ones in rat kidney plasma membrane apical sides (brush-border membranes), liver microsomal membranes and Extensor digitorum longus (EDL) and Soleus (SOL) skeletal muscle tissues. A variety of alterations in the spectral parameters, such as frequency and signal intensity/area was observed in diabetic tissues and membranes compared to the control samples. Based on these spectral variations, using cluster analysis successful differentiation between diabetic and control groups was obtained in different spectral regions. The results of this current study further revealed the power and sensitivity of FT-IR spectroscopy in precise and automated diagnosis of diabetes. PMID- 20575105 TI - Image enhancement in ultramicroscopy by improved laser light sheets. AB - In the majority of implementations of light sheet microscopy, such as ultramicroscopy, the laser beam illuminating the specimen is truncated by a slit aperture before it is focused to a light sheet by a single cylindrical lens. A light sheet generated in this way can be made very thin near to the focal point, but unfortunately its Rayleigh range is severely limited. This problem can be partially solved by using a smaller slit aperture. However, this also causes a major loss in power, a severe broadening of the beam waist, and thus a significant loss of resolution along the detection axis. We developed improved light-sheet-generation optics, which provide longer Raleigh ranges, whilst retaining beam waists comparable to our standard system with one cylindrical lens. Using the modified system we achieved a marked improvement in the resolution of ultramicroscopy reconstructions of representative biological specimens. PMID- 20575106 TI - A fibre optic catheter for simultaneous measurement of longitudinal and circumferential muscular activity in the gastrointestinal tract. AB - Diagnostic catheters based on fibre Bragg gratings (FBG's) are proving to be highly effective for measurement of the muscular activity associated with motility in the human gut. While the primary muscular contractions that generate peristalsis are circumferential in nature, it has long been known that there is also a component of longitudinal contractility present, acting in harmony with the circumferential component to improve the overall efficiency of material movement. We report the detection of longitudinal motion in mammalian intestine using an FBG technique that should be viable for similar detection in humans. The longitudinal sensors have been combined with our previously reported FBG pressure sensing elements to form a composite catheter that allows the relative phase between the two components to be detected. The catheter output has been validated using video mapping in an ex-vivo rabbit ileum preparation. PMID- 20575107 TI - Chemometric analysis of urine fingerprints acquired by liquid chromatography-mass spectrometry and capillary electrophoresis: application to the schistosomiasis mouse model. AB - Urine fingerprints from Schistosoma mansoni infected and control animals were acquired with ultra performance liquid chromatography-MS (UPLC-MS) and compared with the urine fingerprints obtained by CE by applying the same set of multivariate analysis tools. Principal component analysis of the aligned data provided a time trajectory where the infection was observed after 30 days with UPLC-MS and CE. Two main markers describing infected and control, respectively - phenyl acetyl glycine (PAG) and hippurate - were selected to illustrate the use of orthogonal partial least-square discriminant analysis in determining the discriminatory confidence. PAG was found to be significantly related to the disease (high covariance and correlation), whereas hippurate was found to be nonsignificant as an indicator. Orthogonal partial least-square discriminant analysis models were validated for sensitivity and specificity. Multivariate data analysis derived from two different detection systems showed that CE-UV and UPLC MS found equivalent results. This work gives additional mechanistic insight into the progress of the S. mansoni infection; the biochemical role and specificity of PAG as a biomarker is yet to be determined. PMID- 20575108 TI - Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma. AB - The use of lectin affinity chromatography prior to 2-DE separation forms an alternative method to unmask the expression of targeted glycoproteins of lower abundance in serum samples. Reduced expression of alpha-2 macroglobulin (AMG) and complement factor B (CFB) was detected in sera of patients with nasopharyngeal carcinoma (NPC) when pooled serum samples of the patients and those of healthy individuals were subjected to affinity isolation using immobilized champedak mannose-binding lectin and analyzed by 2-DE and densitometry. The AMG and CFB spots were not detected in the 2-DE protein profiles when the same pooled serum samples were subjected to albumin and IgG depletion and neither were they detected when the depleted samples were analyzed by western blotting and lectin detection. Together with other acute-phase response proteins that were previously reported to be altered in expression in NPC patients, AMG and CFB may serve as useful complementary biomarkers for NPC. PMID- 20575109 TI - Externalizing and internalizing behaviors in ASD. AB - The current study investigated the relationships between internalizing and externalizing (I-E) behaviors and family variables, including both parenting stress and quality of attachment relations, in children aged 8-12 with high functioning autism spectrum disorder (ASD) or with typical development. Compared to the group with typical development, children with ASD exhibited significantly greater levels of psychopathology as assessed by the Child Behavior Checklist [Achenbach, 1991], and parents of children with ASD exhibited higher parenting stress as assessed by the Parenting Stress Index [Abidin, 1995]. In a hierarchical multiple regression analysis, parenting stress emerged as the most important predictor of children's I-E problems. Results are discussed in light of the two groups' similar relationships between parenting stress and child psychopathology. PMID- 20575110 TI - Susceptibility to the Shepard illusion in participants with autism: reduced top down influences within perception? AB - Previous research [Ropar & Mitchell, 2002] has shown that autistic individuals are somewhat immune to biases induced by top-down processes, particularly the influence of previous knowledge on perception. In order to test this hypothesis within perception, 18 participants with autism who had measured intelligence in the normal range were compared against 18 matched controls in their susceptibility to the Shepard illusion. The illusion consists in misperceiving the shape of a parallelogram in the presence of depth cues. It is attributed [Mitchell, Ropar, Ackroyd, & Rajendran, 2005] to the effect of top-down constraints within perception. The task involved adjusting a stimulus to the dimensions of a template on a computer screen. Both groups were susceptible to the illusion and the illusion effect was stronger when three-dimensional perspective cues were prominent. Notably, participants with autism were less susceptible to the illusion than typically developing individuals. The findings raise the possibility that in some instances top-down influences are attenuated in individuals with autism. PMID- 20575111 TI - Randomized clinical trial of short-term outcomes following purse-string versus conventional closure of ileostomy wounds. AB - BACKGROUND: Ileostomy closure is an operation with an underappreciated morbidity, including surgical-site infection, small bowel obstruction and anastomotic leakage. Surgical-site infections, in particular, are a frequent occurrence following closure of contaminated wounds. This randomized controlled trial compared a purse-string closure technique with conventional linear closure. METHODS: Sixty-one patients were randomized to conventional or purse-string closure of ileostomy wounds. The primary endpoint was the incidence of surgical site infection, including infections requiring hospital or community treatment. RESULTS: Purse-string closure resulted in fewer surgical-site infections than conventional closure: two of 30 versus 12 of 31 respectively (P = 0.005). CONCLUSION: The purse-string method results in a clinically relevant reduction in surgical-site infections after ileostomy closure. REGISTRATION NUMBER: ACTRN12609000021279 (Australian New Zealand Clinical Trials Registry: http://www.anzctr.org.au/). PMID- 20575113 TI - Laparoscopic aortic surgery. PMID- 20575114 TI - The nickel-catalyzed carbonylative cycloaddition of allyl halides and acetylenes: an efficient tool for cyclopentane annelation. AB - From a practical synthetic point of view, the nickel-mediated carbonylative cycloaddition of alkynes and allyl halides is a straightforward method for obtaining the cyclopentane skeleton in high yields and with controlled stereochemistry, especially when considering the efficiency of the intermolecular version of the reaction. The efforts to make the previously stoichiometric process catalytic in nickel, after experimental mechanistic observations, are reported herein. The unexpected intervention of iron as a reductant and the isolation of a final dimeric species that exhibits interesting tautomeric behavior are also presented. An extension of the reaction to new substrates has led to the conclusion that, although the steric and electronic effects of the alkyne substituents are generally irrelevant in relation to the adducts and their yields, those of the allylic counterpart may have a significant influence on the outcome of the reaction. However, the presence of the amine moiety in the alkyne completely inhibited the reaction. The feasibility of a multicentered reaction was verified with a triacetylene in which up to 12 bonds were created at once and in good yield. PMID- 20575115 TI - Synthesis of hierarchical macro-/mesoporous solid-solution photocatalysts by a polymerization-carbonization-oxidation route: the case of Ce(0.49)Zr(0.37)Bi(0.14)O(1.93). AB - A hierarchical macro-/mesoporous Ce(0.49)Zr(0.37)Bi(0.14)O(1.93) solid-solution network has been synthesized on a large scale by means of a simple and general polymerization-carbonization-oxidation synthetic route. The as-prepared product has been characterized by SEM, XRD, TEM, BET surface area measurement, UV/Vis diffuse-reflectance spectroscopy, energy-dispersive X-ray spectroscopy (EDS), and photoelectrochemistry measurements. The photocatalytic activity of the product has been demonstrated through the photocatalytic degradation of methyl orange. Structural characterization has indicated that the hierarchical macro-/mesoporous solid-solution network not only contains numerous macropores, but also possesses an interior mesoporous structure. The mesopore size and BET surface area of the network have been measured as 2-25 nm and 140.5 m(2) g(-1), respectively. The hierarchical macro-/mesoporous solid-solution network with open and accessible pores was found to be well-preserved after calcination at 800 degrees C, indicating especially high thermal stability. Due to its high specific surface area, the synergistic effect of the coupling of macropores and mesopores, and its high crystallinity, the Ce(0.49)Zr(0.37)Bi(0.14)O(1.93) solid-solution material shows a strong structure-induced enhancement of visible-light harvest and exhibits significantly improved visible-light photocatalytic activity in the photodegradation of methyl orange compared with those of its other forms, such as mesoporous hollow spheres and bulk particles. PMID- 20575116 TI - Cobalt-mediated linear 2:1 co-oligomerization of alkynes with enol ethers to give 1-alkoxy-1,3,5-trienes: a missing mode of reactivity. AB - A variety of 1,6-heptadiynes and certain borylalkynes co-oligomerize with enol ethers in the presence of [CpCo(C(2)H(4))(2)] (Cp=cyclopentadienyl) to furnish the hitherto elusive acyclic 2:1 products, 1,3,5-trien-1-ol ethers, in preference to or in competition with the alternative pathway that leads to the standard [2+2+2] cycloadducts, 5-alkoxy-1,3-cyclohexadienes. Minor variations, such as lengthening the diyne tether, cause reversion to the standard mechanism. The trienes, including synthetically potent borylated derivatives, are generated with excellent levels of chemo-, regio-, and diastereoselectivity, and are obtained directly by decomplexation of the crude mixtures during chromatography. The cyclohexadienes are isolated as the corresponding dehydroalkoxylated arenes. In one example, even ethene functions as a linear cotrimerization partner. The alkoxytrienes are thermally labile with respect to 6pi-electrocyclization elimination to give the same arenes that are the products of cycloaddition. The latter, regardless of the mechanism of their formation, can be viewed as the result of a formal [2+2+2] cyclization of the starting alkynes with acetylene. One-pot conditions for the exclusive formation of arenes are developed. DFT computations indicate that cyclohexadiene and triene formation share a common intermediate, a cobaltacycloheptadiene, from which reductive elimination and beta hydride elimination compete. PMID- 20575117 TI - Design of phase-vanishing reactions. AB - Phase-vanishing reactions utilize a perfluorinated solvent as a liquid membrane to separate a substrate and a reagent. Since their introduction less than ten years ago, phase-vanishing reactions have become a valuable alternative to reactions that require a slow addition of a reagent. A variety of experimental designs allow reactions to be carried out under anhydrous conditions, under photolytic conditions, under solvent-free conditions, with a gas as a reagent, and under reflux. PMID- 20575118 TI - Hydrolysis of organophosphate esters: phosphotriesterase activity of metallo-beta lactamase and its functional mimics. AB - The phosphotriesterase (PTE) activity of a series of binuclear and mononuclear zinc(II) complexes and metallo-beta-lactamase (mbetal) from Bacillus cereus was studied. The binuclear complex 1, which exhibits good mbetal activity, shows poor PTE activity. In contrast, complex 2, a poor mimic of mbetal, exhibits much higher activity than 1. The replacement of Cl(-) ligands by OH(-) is important for the high PTE activity of complex 2 because this complex does not show any catalytic activity in methanol. The natural enzyme mbetal from B. cereus is also found to be an inefficient catalyst in the hydrolysis of phosphotriesters. These observations indicate that the binding of beta-lactam substrates at the binuclear zinc(II) center is different from that of phosphotriesters. Furthermore, phosphodiesters, the products from the hydrolysis of triesters, significantly inhibit the PTE activity of mbetal and its functional mimics. Although the mononuclear complexes 3 and 4 exhibited significant mbetal activity, these complexes are found to be almost inactive in the hydrolysis of phosphotriesters. These observations indicate that the elimination of phosphodiesters from the reaction site is important for the PTE activity of zinc(II) complexes. PMID- 20575119 TI - Vectorial photoinduced energy transfer between boron-dipyrromethene (Bodipy) chromophores across a fluorene bridge. AB - A series of novel multichromophoric, luminescent compounds has been prepared, and their absorption spectra, luminescence properties (both at 77 K in rigid matrix and at 298 K in fluid solution), and photoinduced intercomponent energy-transfer processes have been studied. The series contains two new multichromophoric systems 1 and 2, each one containing two different boron-dipyrromethene (Bodipy) subunits and one bridging fluorene species, and two fluorene-Bodipy bichromophoric species, 6 and 7. Three monochromophoric compounds, 3, 4, and 5, used as precursors in the synthetic process, were also fully characterized. The absorption spectra of the multichromophoric compounds are roughly the summation of the absorption spectra of their individual components, thus demonstrating the supramolecular nature of the assemblies. Luminescence studies show that quantitative energy transfer occurs in 6 and 7 from the fluorene chromophore to the Bodipy dyes. Luminescence studies, complemented by transient-absorption spectroscopy studies, also indicate that efficient inter-Bodipy energy transfer across the rigid fluorene spacer takes place in 1 and 2, with rate constants, evaluated by several experimental methods, between 2.0 and 7.0 x 10(9) s(-1). Such an inter-Bodipy energy transfer appears to be governed by the Forster mechanism. By taking advantage of the presence of various protonable sites in the substituents of the lower-energy Bodipy subunit of 1 and 2, the effect of protonation on the energy-transfer rates has also been investigated. The results suggest that control of energy-transfer rate and efficiency of inter-Bodipy energy transfer in this type of systems can be achieved by an external, reversible input. PMID- 20575120 TI - Polyelectrolyte-assisted formation of molecular nanoparticles exhibiting strongly enhanced fluorescence. AB - A polyelectrolyte-assisted reprecipitation method is developed to fabricate nanoparticles of highly soluble molecules. The approach is demonstrated by using a zwitterionic diaminodicyanoquinodimethane molecule bearing remote ammonium functionalities with high solubility in water as well as organic solvents. Nanoparticles are prepared by injecting aqueous solutions of this compound containing an optimum concentration of sodium poly(styrenesulfonate) into methanol. The strong fluorescence exhibited by the compound in the aggregated state is reflected in the enhanced fluorescence of the polyelectrolyte complex in water. The nanoparticles formed in the colloidal state manifest even stronger fluorescence, which leads to an overall enhancement by about 90 times relative to aqueous solutions of the pure compound. The conditions for achieving the emission enhancement are optimized and a model for the molecular-level interactions and aggregation effects is developed through a range of spectroscopy, microscopy, and calorimetry investigations and control experiments. PMID- 20575121 TI - The cobalt way to angucyclinones: asymmetric total synthesis of the antibiotics (+)-rubiginone B2, (-)-tetrangomycin, and (-)-8-O-methyltetrangomycin. AB - A cobalt(I)-mediated convergent and asymmetric total synthesis of angucyclinones with an aromatic B ring has been developed. In the course of our research, we synthesized three naturally occurring anguclinone derivatives, namely, (+) rubiginone B(2) (1), (-)-8-O-methyltetrangomycin (2), and (-)-tetrangomycin (3). By combining 3-hydroxybenzoic acid, 3-methoxybenzoic acid, citronellal, and geraniol as starting materials in a convergent way, we were able to synthesize chiral triyne chains, which were cyclized with [CpCo(C(2)H(4))(2)] (Cp=cyclopentadienyl) by means of an intramolecular [2+2+2] cycloaddition to their corresponding tetrahydrobenzo[a]anthracenes. Successive oxidation and deprotection steps led to the above-mentioned natural products 1-3. PMID- 20575122 TI - In vivo double and triple labeling of proteins using synthetic amino acids. PMID- 20575123 TI - [An(H2O)9](CF3SO3)3 (An=U-Cm, Cf): exploring their stability, structural chemistry, and magnetic behavior by experiment and theory. PMID- 20575124 TI - Robust generation of lead compounds for protein-protein interactions by computational and MCR chemistry: p53/Hdm2 antagonists. PMID- 20575125 TI - Assessment of tumor metastasis by the direct determination of cell-membrane sialic acid expression. PMID- 20575126 TI - Facile synthesis of isomerically pure fullerenols and formation of spherical aggregates from C60(OH)8. PMID- 20575127 TI - Highly stereoselective synthesis of substituted prolyl peptides using a combination of biocatalytic desymmetrization and multicomponent reactions. PMID- 20575128 TI - Bis(1,3-trimethylsilylallyl)beryllium. PMID- 20575129 TI - Monolithic and flexible polyimide film microreactors for organic microchemical applications fabricated by laser ablation. PMID- 20575130 TI - Facile synthesis of five-fold twinned, starfish-like rhodium nanocrystals by eliminating oxidative etching with a chloride-free precursor. PMID- 20575131 TI - Unusual eta2-allene osmacycle with apoptotic properties. AB - Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in HeLa cells led to the discovery of a highly cytotoxic eta2-allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a sigma-bond to a carbon in combination with coordination to an allene moiety. The osmacycle strongly induces apoptosis in Burkitt-like lymphoma cells at submicromolar concentrations. The reduction of the mitochondrial membrane potential, the induction of DNA fragmentation, and the activation of caspases-9 and -3 reveal that programmed cell death occurs through the intrinsic mitochondrial pathway. From the lipophilic and cationic nature of the osmacycle, in addition to a low oxidation potential (E1/2=+0.27 V vs. Fc/Fc+, Fc=ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis. PMID- 20575132 TI - Delivery of oligonucleotides and analogues: the oligonucleotide conjugate-based approach. PMID- 20575133 TI - A novel cyanobacterial nostocyclopeptide is a potent antitoxin against microcystins. AB - Cyanobacterial hepatotoxins (microcystins and nodularins) cause numerous animal poisonings worldwide each year and are threats to human health. However, we found that extracts from several cyanobacteria isolates failed to induce hepatotoxicity even if they contained high concentrations of the liver toxin microcystin. The antitoxic activity abolishes all morphological hallmarks of microcystin-induced apoptosis, and therefore invalidates cell-based assays of the microcystin content of bloom-forming cyanobacteria. The antitoxin was purified from a cyanobacterial isolate (Nostoc sp. XSPORK 13A) from the Baltic Sea, and the activity was shown to reside in a novel cyclic peptide of the nostocyclopeptide family (nostocyclopeptide M1, Ncp-M1) that consists of seven amino acids (Tyr1-Tyr2-D HSe3-L-Pro4-L-Val5-(2S,4S)-4-MPr6-Tyr7; MW=881) with an imino linkage between Tyr1 and Tyr7. Ncp-M1 did not compete with labelled microcystin for binding to protein phosphatase 2A; this explains why the antitoxin did not interfere with phosphatase-based microcystin assays. Currently used agents that interfere with microcystin action, such as inhibitors of ROS formation, microcystin uptake and Cam-kinase activity, are themselves inherently toxic. Since Ncp-M1 is potent and nontoxic it promises to become a useful mechanistic tool as soon as its exact cellular target is elucidated. PMID- 20575134 TI - Cross-linked peptoid-based dimerization inhibitors of HIV-1 protease. PMID- 20575135 TI - First heterologous reconstruction of a complete functional fungal biosynthetic multigene cluster. PMID- 20575136 TI - Characterizing single-molecule FRET dynamics with probability distribution analysis. AB - Probability distribution analysis (PDA) is a recently developed statistical tool for predicting the shapes of single-molecule fluorescence resonance energy transfer (smFRET) histograms, which allows the identification of single or multiple static molecular species within a single histogram. We used a generalized PDA method to predict the shapes of FRET histograms for molecules interconverting dynamically between multiple states. This method is tested on a series of model systems, including both static DNA fragments and dynamic DNA hairpins. By fitting the shape of this expected distribution to experimental data, the timescale of hairpin conformational fluctuations can be recovered, in good agreement with earlier published results obtained using different techniques. This method is also applied to studying the conformational fluctuations in the unliganded Klenow fragment (KF) of Escherichia coli DNA polymerase I, which allows both confirmation of the consistency of a simple, two state kinetic model with the observed smFRET distribution of unliganded KF and extraction of a millisecond fluctuation timescale, in good agreement with rates reported elsewhere. We expect this method to be useful in extracting rates from processes exhibiting dynamic FRET, and in hypothesis-testing models of conformational dynamics against experimental data. PMID- 20575137 TI - Chemistry of O- and H-containing species on the (001) surface of anatase TiO2: a DFT study. AB - The chemistry of oxygen, hydrogen, water, and other species containing both oxygen and hydrogen atoms on the anatase TiO(2) (001) surface is investigated by DFT. The adsorption energy of atoms and radicals depends appreciably on the position and mode of adsorption, and on the coverage. Molecular hydrogen and oxygen interact weakly with the clean surface. However, H(2)O dissociates spontaneously to give two nonidentical hydroxyl groups, and this provides a model for hydroxylation of TiO(2) surfaces by water. The mobility of the hydroxyl groups created by water splitting is initially impeded by a diffusion barrier close to 1 eV. The O(2) adsorption energy increases significantly in the presence of H atoms. Hydroperoxy (OOH) formation is feasible if at least two H atoms are present in the direct vicinity of O(2). In the adsorbed OOH, the O-O bond is considerably lengthened and thus weakened. PMID- 20575138 TI - Stability of gold and platinum nanowires on graphite edges. AB - The stability of coinage and noble metal nanowires supported on graphite steps is examined by density functional theory. In particular, we study the stability of supported gold and platinum wires and compare their chemical properties with those of surfaces and bare wires. A substantially stronger bond with graphite was found for platinum wires due to unfilled antibonding states, which are occupied in the case of gold. This difference has direct consequences for the adsorption of hydrogen. This reaction can occur either on the wire or directly on graphite steps. In the case of gold, the reaction is favoured on steps, while on platinum wires, it has no thermodynamical preferences. Our results suggest that, in early stages of wire formation, hydrogen could desorb gold from graphite, but not platinum. PMID- 20575140 TI - Synthesis of bioactive 2-aza-analogues of ipecac and alangium alkaloids. PMID- 20575141 TI - Logic information communication in a fluorescent molecular switch. AB - Based on the chemical-sensitive fluorescence emission behaviors of the molecular switch 4-bromo-5-methoxy-2-(2-pyridyl)thiazole (2-BMPT), the communication of logic information between two functional units has been realized. With the rational control of the protonation and coordination reaction of 2-BMPT, an upstream switching unit (a 1:2 demultiplexer) and two downstream data-processing units are involved and interconnected in the communication. The two output states of the 1:2 demultiplexer serve as the initial input states of the two parallel downstream data-processing units, which execute the information communication between the two circuit layers. Furthermore, in the parallel data-processing layer, the logic gates of INHIBIT and YES accomplish their specific logic functions. Therefore, a molecular cascade circuit composed of an upstream switch and two downstream processing units has been constructed based on the chemical modulated fluorescence properties of 2-BMPT. PMID- 20575139 TI - Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds. AB - Apicomplexan parasites encompass several human- and animal-pathogenic protozoans such as Plasmodium falciparum, Toxoplasma gondii, and Eimeria tenella. E. tenella causes coccidiosis, a disease that afflicts chickens, leading to tremendous economic losses to the global poultry industry. The considerable increase in drug resistance makes it necessary to develop new therapeutic strategies against this parasite. Cyclin-dependent kinases (CDKs) are key molecules in cell-cycle regulation and are therefore prominent target proteins in parasitic diseases. Bioinformatics analysis revealed four potential CDK-like proteins, of which one E. tenella CDK-related kinase 2 (EtCRK2)-has already been characterized by gene cloning and expression.1 By using the CDK-specific inhibitor flavopiridol in EtCRK2 enzyme assays and schizont maturation assays (SMA), we could chemically validate CDK-like proteins as potential drug targets. An X-ray crystal structure of human CDK2 (HsCDK2) served as a template to build protein models of EtCRK2 by comparative homology modeling. Structural differences in the ATP binding site between EtCRK2 and HsCDK2, as well as chicken CDK3, were addressed for the optimization of selective ATP-competitive inhibitors. Virtual screening and "wet bench" high-throughput screening campaigns on large compound libraries resulted in an initial set of hit compounds. These compounds were further analyzed and characterized, leading to a set of four promising lead compounds for development as EtCRK2 inhibitors. PMID- 20575142 TI - Carbon dioxide capture on amine-rich carbonaceous materials derived from glucose. AB - The synthesis of carbonaceous materials with a high surface density of amino functions for CO(2) sorption and sequestration is reported. The amino-rich carbonaceous materials are characterized by elemental analysis, N(2) sorption, scanning and transmission electron microscopy, zeta potential, TGA and FTIR measurements. A detailed discussion on the use of these materials in CO(2) capture is provided. The materials show significant sorption capabilities for CO(2) (4.3 mmol g(-1)at -20 degrees C and 1 bar). Furthermore, they show a high apparent selectivity for CO(2) over N(2) at both low and high temperatures. PMID- 20575143 TI - Steam-stripping for regeneration of supported amine-based CO(2) adsorbents. PMID- 20575146 TI - Prenatal sonographic findings associated with fibroepithelial stromal polyp of the vulva. PMID- 20575144 TI - Coordination of a complex welfare system case: rehabilitation entity in Finland. AB - The main purpose of this article is to analyse the institutional and political structures of the Finnish rehabilitation entity and the governmental efforts to improve the governance of the rehabilitation policy. Rehabilitation in Finland is a complex welfare system which has undergone several coordination attempts during the last two decades. The centrality of the coordination of this welfare system is obvious. Based on the content analysis of three Government's rehabilitation reports from 1994 to 2002 and their background papers, this article provides two main findings. First, the rehabilitation entity seems to be based on different funding strategies, different governing and different coordination models between the rehabilitation subsystems. Second, the governance discourse in the reports seems to be unchanging with a predominantly hierarchical mode. The article concludes with a discussion on the challenges to coordinate this kind of a complex welfare system as an entity and also how to overcome those challenges. PMID- 20575147 TI - Preparation of defined human embryonic stem cell populations for transcriptional profiling. AB - This unit describes a useful approach to preparing highly reproducible samples of human embryonic stem cell (hESC) total RNA suitable for transcriptional profiling from heterogeneous mixtures of cells containing undifferentiated hESC and differentiated cell types. In this unit, fluorescence-activated cell sorting (FACS) is used to sub-fractionate hESC populations on the basis of their levels of co-expression of two previously published hESC surface markers, CD9(TG30) and GCTM-2. This sub-fractionation allows for the separation of undifferentiated hESC (CD9hi, GCTM-2hi) from the early stages in hESC differentiation (CD9neg or low, GCTM-2neg or low). PMID- 20575148 TI - Down syndrome screening using first-trimester combined tests and contingent use of femur length at routine anomaly scan. AB - OBJECTIVE: The objective of this study was to evaluate the performance of the contingent use of femur length (FL) at routine mid-trimester scan in screening for Down syndrome (DS) in women having previously undergone first-trimester screening with disclosure of risk estimates. METHODS: Data from a prospective screening trial for DS in a population of 21 492 women with 80 observed DS were used. The performance of a contingent screening strategy based on adding short FL (FL < 5th percentile) as a soft marker in women at intermediate first-trimester risks was evaluated through simulated data. RESULTS: In our population, the median (25th-75th percentile) maternal age was 30.7 years (28.0-33.9; range: 18.0 46.3). The median (25th-75th percentile) gestational age at ultrasound examination was 12 weeks 3 days (12 weeks and 12 weeks 6 days; range: 11 weeks to 13 weeks 6 days). Contingent screening allowed an improvement in screening performance. For example, using a first-trimester risk cut-off of 1/100 and an intermediate-risk population within (1/1000, 1/100) for the search of FL, a sensitivity (Se) of 88.4% at a 3% false-positive rate (FPR) was reached. With a cut-off of 1/200 and an intermediate-risk population within (1/1000, 1/200), screening would allow an Se of 92.3% at a 4% FPR. CONCLUSIONS: Contingent screening could be used following first-trimester combined screening followed by second-trimester ultrasound soft markers. This could identify indications for early invasive testing in the highest risk cases and would allow efficient and simple ultrasound-based screening in the second trimester. This would provide an 88.4% Se for a 3% FPR, at no additional cost as compared to first-trimester combined screening and routine mid-trimester scan. PMID- 20575149 TI - Saving lives versus life-years in rural Bangladesh: an ethical preferences approach. AB - Using a random sample of individuals in rural Bangladesh, this paper investigates people's ethical preferences regarding relative values of lives when it comes to saving lives of individuals of different ages. By assuming that an individual has preferences concerning different states of the world, and that these preferences can be described by an individual social welfare function, the individuals' preferences for life-saving programs are elicited using a pair-wise choice experiment involving different life-saving programs. In the analyses, we calculate the social marginal rates of substitution between saved lives of people of different ages. We also test whether people have preferences for saving more life-years rather than only saving lives. In particular, we test and compare the two hypotheses that only lives matter and that only life-years matter. The results indicate that the value of a saved life decreases rapidly with age and that people have strong preferences for saving life-years rather than lives per se. Overall, the results clearly show the importance of the number of life-years saved in the valuation of life. PMID- 20575150 TI - Ultrasound screening for fetal aneuploidy using soft markers in the overweight and obese gravida. AB - OBJECTIVE: To determine the completion rate of ultrasound surveys for aneuploidy markers by maternal body mass index (BMI). METHODS: A retrospective review of ultrasounds on midtrimester singleton pregnancies was performed. Subjects were grouped as normal, overweight (BMI 25-29.9 kg/m(2)), and obese: class I (30-34.9 kg/m(2)), class II (35-39.9 kg/m(2)), and class III (>or= 40 kg/m(2)). Examinations with visualization of at least seven of eight markers were considered complete. RESULTS: Of 14 353 ultrasounds reviewed, 5690 patients were eligible: 43% normal, 29% overweight, 27% obese. Completion rates differed significantly between groups (64% normal, 64% overweight, 61% class I, 55% class II, 47% class III, p < 0.001). The screen positive rates (>or=1 marker) differed significantly overall (16% normal, 13% overweight, 15% class I, 12% class II, 10% class III, p < 0.02), but not for complete examinations (p = 0.42). CONCLUSIONS: Since completion rates for ultrasound aneuploidy screening are inversely related to maternal obesity, obese women are underscreened. PMID- 20575151 TI - The efficiency frontier approach to economic evaluation of health-care interventions. AB - BACKGROUND: IQWiG commissioned an international panel of experts to develop methods for the assessment of the relation of benefits to costs in the German statutory health-care system. PROPOSED METHODS: The panel recommended that IQWiG inform German decision makers of the net costs and value of additional benefits of an intervention in the context of relevant other interventions in that indication. To facilitate guidance regarding maximum reimbursement, this information is presented in an efficiency plot with costs on the horizontal axis and value of benefits on the vertical. The efficiency frontier links the interventions that are not dominated and provides guidance. A technology that places on the frontier or to the left is reasonably efficient, while one falling to the right requires further justification for reimbursement at that price. This information does not automatically give the maximum reimbursement, as other considerations may be relevant. Given that the estimates are for a specific indication, they do not address priority setting across the health-care system. CONCLUSION: This approach informs decision makers about efficiency of interventions, conforms to the mandate and is consistent with basic economic principles. Empirical testing of its feasibility and usefulness is required. PMID- 20575152 TI - Health aid and governance in developing countries. AB - Despite anecdotal evidence that the quality of governance in recipient countries affects the allocation of international health aid, there is no quantitative evidence on the magnitude of this effect, or on which dimensions of governance influence donor decisions. We measure health-aid flows over 1995-2006 for 109 aid recipients, matching aid data with measures of different dimensions of governance and a range of country-specific economic and health characteristics. Everything else being equal, countries with more political rights receive significantly more aid, but so do countries with higher corruption levels. The dependence of aid on political rights, even when we control for other governance indicators, suggests that health aid is sometimes used as an incentive to reward political reforms. PMID- 20575153 TI - Effectiveness of crosstrimester test in selecting high-risk pregnant women to undergo invasive prenatal diagnosis. PMID- 20575154 TI - I'm lactose intolerant. Are there any dairy products that won't make me feel sick? PMID- 20575155 TI - Bright, non-blinking, and less-cytotoxic SiO2 beads with multiple CdSe/ZnS nanocrystals. AB - A method including surface silanization, phase transfer and self-assembly, and SiO2 shell growth has been developed to incorporate multiple hydrophobic CdSe/ZnS nanocrystals into SiO2 beads where they are well suited for bio-application due to their high brightness, less-cytotoxic, and non-blinking nature. PMID- 20575156 TI - Cytokine levels increase risk for non-Hodgkin lymphoma. PMID- 20575157 TI - Once-daily dosing of lopinavir/ritonavir (Kaletra) receives FDA approval. PMID- 20575158 TI - Bioequivalent formulation for the fixed-dose regimen of Truvada and TMC278 finalized. PMID- 20575160 TI - HIV places burden on primary care physicians. PMID- 20575159 TI - Rates of HIV infection in gay and bisexual men hit alarming levels in Asia. PMID- 20575162 TI - [What is Marshall Protocol--and how can we use it?]. PMID- 20575163 TI - The intestinal fatty acid binding protein diagnosing gut dysfunction in acute pancreatitis: a pilot study. AB - OBJECTIVES: To study the use of intestinal fatty acid binding protein (I-FABP) in diagnosing gut dysfunction in patients with acute pancreatitis (AP). METHODS: Thirty-two patients with AP onset within 7 days were enrolled in our study. The severity of disease and the gut dysfunction were evaluated as follows: on admission, on the seventh day of disease attack, and on the third day after enteral nutrition. Serum levels of I-FABP, citrulline, and C-reactive protein (CRP) and the lactulose and mannitol absorption ratio in urine were measured in parallel. RESULTS: The serum level of I-FABP increased on admission, and it was more pronounced in severe attacks. All patients had increased gut dysfunction score, serum level of CRP, and urine level of lactulose and mannitol absorption ratio with decreased serum level of citrulline. A positive correlation was found between the following pairs of measurement on admission: serum level of I-FABP and gut dysfunction score, serum level of I-FABP and Acute Physiology and Chronic Health Evaluation II score, I-FABP and serum level of CRP, and serum level of I FABP and the length of ICU stay. A reverse correlation between the serum level of I-FABP and the serum level of citrulline was found. CONCLUSIONS: The serum level of I-FABP can be used for assessing the gut dysfunction and disease severity of AP. PMID- 20575164 TI - Frequently discordant results from therapeutic drug monitoring for digoxin: clinical confusion for the prescriber. AB - BACKGROUND: Digoxin remains a commonly prescribed medication for the treatment of congestive cardiac failure or atrial tachyarrhythmias. Its utility is offset by its narrow therapeutic index requiring regular blood concentration monitoring. Recent evidence suggests that a lower therapeutic range (0.5- 0.8 mg/L, or 0.6 1.0 nmol/L) is associated with reduced mortality in patients with congestive cardiac failure. Therapeutic drug monitoring for digoxin is carried out by immunoassays that are well established in routine clinical practice. Laboratories using different immunoassays may be involved in monitoring individual patients throughout the protracted course of therapy. These results should be concordant to ensure consistent dose individualization and optimum clinical management. We have investigated the discordance in digoxin measurements involving five different laboratories across the Adelaide metropolitan area. METHODS: Aliquots from routine digoxin samples (n = 261) were analysed by accredited laboratories using commercially available immunoassays. RESULTS: The results showed that 119 (46%) of 261 samples were so varied that a different clinical outcome was indicated when reviewed by the treating physician. The differences between the highest and lowest readings from any one sample were also substantial, with 45% of the measurements exceeding 0.3 microg/L. CONCLUSIONS: Our study shows the considerable variation in the routine monitoring of digoxin. This makes therapeutic drug monitoring difficult to interpret and complicates clinical management when treating physicians are endeavouring to avoid toxicity and optimize dosing. These results raise a significant concern for the quality of therapeutic drug monitoring of digoxin and have direct repercussions on patient care. PMID- 20575165 TI - Daily exercise prescription on the basis of HR variability among men and women. AB - PURPOSE: To test the utility of HR variability (HRV) in daily exercise prescription in moderately active (approximately two exercises per week) men and women. METHODS: A total of 21 men and 32 women were divided into standard training (ST: males = 7 and females = 7), HRV-guided training (HRV-I: males = 7 and females = 7; HRV-II: females = 10), and control (males = 7 and females = 8) groups. The 8-wk aerobic training period included 40-min exercises at moderate and vigorous intensities (70% and 85% of maximal HR). The ST group was instructed to perform two or more sessions at moderate and three or more sessions at vigorous intensity weekly. HRV-I and HRV-II groups trained on the basis of changes in HRV, measured every morning. In the HRV-I group, an increase or no change in HRV resulted in vigorous-intensity training on that day. Moderate intensity exercise or rest was prescribed if HRV had decreased. The HRV-II group performed a vigorous-intensity exercise only when HRV had increased. Peak oxygen consumption (VO2peak) and maximal workload (Loadmax) were measured by a maximal bicycle ergometer test before and after the intervention. RESULTS: The changes in VO2peak did not differ between the training groups either in men or in women. In men, the change in Loadmax was higher in the HRV-I group than in the ST group (30 +/- 8 vs 18 +/- 10 W, P = 0.033). In women, no differences were found in the changes in Loadmax between the training groups (18 +/- 10, 15 +/- 11, and 18 +/- 5 W for ST, HRV-I, and HRV-II, respectively). The HRV-II group performed fewer vigorous-intensity exercises than the ST and HRV-I groups (1.8 +/- 0.3 vs 2.8 +/- 0.6 and 3.3 +/- 0.2 times per week, respectively, P < 0.01 for both). CONCLUSIONS: HRV measurements are beneficial in exercise training prescription in moderately active men and women. Women benefit from HRV guidance by achieving significant improvement in fitness with a lower training load. PMID- 20575166 TI - Deaf culture meets nursing culture. PMID- 20575170 TI - A diagnosis of Asperger's syndrome. PMID- 20575175 TI - The state of midwifery in Iceland. PMID- 20575176 TI - Acknowledging maternal mortality in Uganda. PMID- 20575177 TI - Oxidative dimerization of N-protected and free indole derivatives toward 3,3 biindoles via Pd-catalyzed direct C-H transformations. AB - An oxidative homo dimerization of N-protected and free indole derivatives toward bioactive 3,3-linked biindolyl scaffolds via Pd-catalyzed direct C-H transformations was first successfully demonstrated. PMID- 20575178 TI - [Mercury speciation in aquatic products analyzed by liquid chromatography cold vapor atomic fluorescence spectrometry]. AB - OBJECTIVE: To establish a method for the detection of mercury species in aquatic products by liquid chromatography online coupled with cold vapor atomic fluorescence spectrometry(LC-CV-AFS) and to participate in the international proficiency tests to verify the method. METHODS: Mercury species were extracted from aquatic samples by using ultrasonication-assisted acid extraction, separated by reversed phase liquid chromatography, decomposed into inorganic mercury ion with on line UV digestion system, and then determined by cold vapor atomic fluorescence spectrometry. RESULTS: Methylmercury, ethylmercury and inorganic mercury were baseline separated within 20 minutes. The linear range was 1-20 microg/L for the three species and the correlation coefficient r > or = 0.999. The detection limits for methylmercury, ethylmercury and inorganic mercury were 1 microg/kg, 2 microg/kg and 1 microg/kg respectively. The recovery of samples for three spiked levels (10, 50 and 500 microg/kg) was in the range of 89%-106%. The relative standard deviations (RSDs) were less than 10%. The determined methylmercury contents of certified reference materials (CRMs) were agreed well with the certified values. The results of determined methylmercury values were satisfied (Z <2) in two international proficiency tests, i.e., Food Analysis Performance Assessment Scheme (FAPAS, UK)-07115 test and International Atomic Energy Agency (IAEA)-452 test. CONCLUSION: The LC-CV-AFS method is simple, sensitive and accurate and could meet the demand for mercury speciation in aquatic products. PMID- 20575179 TI - Sidelined for safety: new laws keep student athletes with concussions benched. PMID- 20575180 TI - Overhaul Rx: lawmakers have plenty of work ahead to comply with the new federal health care law. PMID- 20575181 TI - Services for mental illness. PMID- 20575182 TI - Special report: vaccines for the treatment of prostate cancer. PMID- 20575183 TI - Percutaneous vertebroplasty or kyphoplasty for vertebral fractures caused by osteoporosis. PMID- 20575184 TI - Establishment of the temporary certification program for health information technology. Final rule. AB - This final rule establishes a temporary certification program for the purposes of testing and certifying health information technology. This final rule is established under the authority granted to the National Coordinator for Health Information Technology (the National Coordinator) by section 3001(c)(5) of the Public Health Service Act (PHSA), as added by the Health Information Technology for Economic and Clinical Health (HITECH) Act. The National Coordinator will utilize the temporary certification program to authorize organizations to test and certify Complete Electronic Health Records (EHRs) and/or EHR Modules, thereby making Certified EHR Technology available prior to the date on which health care providers seeking incentive payments available under the Medicare and Medicaid EHR Incentive Programs may begin demonstrating meaningful use of Certified EHR Technology. PMID- 20575185 TI - Cardiac resynchronization therapy for mild congestive heart failure. PMID- 20575186 TI - Accelerated radiotherapy after breast-conserving surgery for early stage breast cancer. PMID- 20575187 TI - Special report: laboratory testing to allow area under the curve (AUC)-targeted 5 fluorouracil dosing for patients administered chemotherapy for cancer. PMID- 20575188 TI - Parenteral nutrition: future directions. PMID- 20575189 TI - Better is the enemy of good. PMID- 20575190 TI - The baby with the bathwater. PMID- 20575191 TI - Finding the problems before fixing them: the culture of perioperative safety. PMID- 20575192 TI - The dimensions of the roots of the human permanent dentition as a guide to the selection of optimal orthodontic forces. AB - BACKGROUND: The dimensions of the roots of the teeth are important in the assessment of orthodontic anchorage and to estimate the forces to be used during orthodontic tooth movement. AIMS: To investigate the relations between the lengths, widths and projected areas of the roots of the permanent teeth. METHODS: Intact, extracted human permanent teeth were photographed and the lengths, widths and projected areas of selected surfaces measured. Descriptive statistics and associations between selected linear dimensions and root areas were calculated. RESULTS: The data showed significant kurtosis and skewness. Neither exponential nor polynomial transformations improved the goodness of fit, and there was no a priori reason to use other than linear regression. When the lengths of all teeth were multiplied by the respective widths of the mesial, distal and lingual surfaces, the correlations between the product of length and width and area improved in 28 out of 30 surfaces. In the lower arch the correlation coefficients ranged from r = .343 (mesial surface first premolar) to r = .845 (mesial surface of the canine). The correlations in the upper arch ranged from r = .201 (mesial surface of the second molar) to r = .847 (mesial surface lateral incisor). CONCLUSIONS: For clinical purposes, root length may be an acceptable indicator of root area. Low correlations were attributed to variations in root shape. PMID- 20575193 TI - Amorphous calcium phosphate-containing orthodontic composites. Do they prevent demineralisation around orthodontic brackets? AB - BACKGROUND: A preliminary study using laser fluorescence suggested that amorphous phosphate-containing orthodontic composites may prevent demineralisation around bonded orthodontic brackets. OBJECTIVE: To compare the microhardness of the enamel around brackets bonded with an amorphous calcium phosphate-containing orthodontic composite (ACP-containing) with the microhardness of the enamel around brackets bonded with a conventional composite resin. METHODS: Forty extracted upper premolars were used. Orthodontic brackets were bonded to the teeth with either an ACP-containing composite resin (N = 20) or a conventional composite resin (N = 20). The latter were used as the control. The crowns of all teeth were painted with an acid resistant varnish, leaving a 2 mm ring of exposed enamel around the brackets. The teeth were then subjected to a daily cycle of demineralisation for 6 hours and remineralisation for 18 hours for 21 days. Each tooth was sectioned and the microhardness of the enamel determined 25, 50, 75, 100 and 150 microm from the surface. RESULTS: The enamel was significantly harder 25 microm (p = 0.000) and 50 microm (p = 0.001) from the enamel surface in the teeth with brackets bonded with the ACP-containing composite resin as compared with the control teeth. CONCLUSION: ACP-containing orthodontic composite resins may reduce the enamel decalcification found in patients with poor oral hygiene. PMID- 20575194 TI - Cytotoxicity of orthodontic separating elastics. AB - BACKGROUND: Separating elastics may be cytotoxic to the interdental gingival tissues. Both latex and non-latex separating elastics are widely used and both types should be biocompatible. OBJECTIVE: To determine if latex and non-latex orthodontic separating elastics are cytotoxic. METHODS: The cytotoxicity of natural latex (Groups A, D and O) and non-latex (Group M) orthodontic separating elastics were determined by incubating 15 elastics of each type in Eagle's essential medium (MEM), removing the supernatant after 24, 48, 72 and 168 hours and adding it to cultures of L-929 mouse fibroblasts in growth medium (MEM plus glutamine, garamicine, fungizone, sodium bicarbonate, buffered saline and foetal calf serum). To verify the cell response in extreme situations, three additional groups were included: Group CC (cell control), consisting of L-929 cells not exposed to supernatants from the maintenance medium with the elastics; Group C+ (positive control), consisting of Tween 80; Group C- (negative control), consisting of phosphate buffered saline solution. The positive and negative controls were incubated in MEM maintenance medium for 24, 48, 72 and 168 hours and the extracted elutes were added to L-929 line cells incubated in the growth medium. The viability of the cells was determined with neutral red (dye-uptake method) at 24, 48, 72 and 168 hours. The data were analysed with the analysis of variance (ANOVA) and Tukey's multiple comparison test. The significance level was p < or = 0.05. RESULTS: The elastics in Groups A, D and O induced greater cell lysis at 72 hours compared to the other experimental times. There were statistically significant differences between the cytotoxicity of the elastics in Groups A, D and O in relation to Group CC for experimental times of 24, 48, 72 and 168 hours (p > 0.05). There was not, however, a statistically significant difference between Groups D and CC at 24 hours. CONCLUSION: The latex and non latex orthodontic separating elastics tested were considered to be biocompatible. PMID- 20575195 TI - Porcelain brackets during initial alignment: are self-ligating cosmetic brackets more efficient? AB - OBJECTIVE: To compare the effectiveness of a self-ligating (SL) porcelain bracket with a conventional porcelain (CP) bracket tied with ligatures for initial alignment in the upper arch, to compare the discomfort of both bracket - archwire combinations and to compare the times taken (both assisted and unassisted) to untie and ligate both bracket - archwire combinations. METHODS: Sixty nonextraction patients were randomly assigned to either a group with CP brackets on the upper six anterior teeth and conventional metal brackets on the premolars and first molars, or a group with SL porcelain brackets on the anterior teeth and SL metal brackets on the posterior teeth. The CP brackets were tied with coated ligatures. The irregularity index was measured at the start of treatment and at the first recall 10.7 weeks later. Discomfort was recorded over the first week with a Likert scale and the times to untie and ligate the six anterior porcelain brackets (assisted and unassisted) were recorded. RESULTS: There were no differences in irregularities at the start of treatment (p = 0.91) or 10.7 weeks later (p = 0.12). No significant difference in discomfort was found between the bracket types (p = 0.90). The porcelain SL brackets were significantly faster (p < 0.001) to untie and ligate than the CP brackets with ligatures. CONCLUSION: Porcelain SL brackets were faster to untie and ligate by 22 seconds per bracket, but there were no significant differences in the alignment achieved or discomfort experienced. PMID- 20575196 TI - Display of the incisors as functions of age and gender. AB - BACKGROUND: Older subjects usually show less of their upper incisors and more of their lower incisors than younger subjects. OBJECTIVES: To determine how much of the upper and lower central incisor crowns are visible in Brazilian subjects with their lips at rest. METHODS: The subjects were 240 white Brazilian subjects divided into four age groups: Group 1, 12 to 15 years of age; Group 2, 20 to 30 years of age; Group 3, 31 to 50 years of age and Group 4, 51 years of age and older. Each group contained 30 males and 30 females. The vertical display of the incisors was measured in millimetres from the midpoints of the incisal edges of the upper and lower central incisors to the borders of the upper and lower lips. RESULTS: In females, the mean upper central incisor display reduced from 4.45 mm in Group 1 to 1.32 mm in Group 4, and in males it reduced from 3.35 mm in Group 1 to 0.57 mm in Group 4. Less of the lower central incisor crowns were displayed in Group 1 females (Mean: 0.47 mm) than in Group 4 females (Mean: 2.22 mm), and in Group 1 males (Mean: 0.61 mm) than in Group 4 males (Mean: 3.05 mm). Brazilian women showed significantly more of their upper incisor crowns than Brazilian men in Groups 1, 2 and 4, whereas Brazilian men showed significantly more of their lower central incisors than Brazilian women in Group 4. CONCLUSIONS: With the lips at rest, older Brazilians display less of their upper central incisors and more of their lower central incisors than young Brazilians. Women show more of their upper incisors than men, while men display more of their lower central incisors than women. PMID- 20575197 TI - McNamara norms for Turkish adolescents with balanced faces and normal occlusion. AB - BACKGROUND: There are no norms for the McNamara analysis for Turkish adolescents. OBJECTIVE: To obtain cephalometric standards for the McNamara analysis for Turkish adolescents with balanced faces and Class I occlusions, and to compare the standards with published data. METHODS: The cephalometric radiographs of 116 children (83 female, 33 male) between 11 and 16 years of age with Turkish grandparents and Class I occlusion, well-aligned upper and lower dental arches, no anterior and/or posterior crossbites and normal dentofacial structures were used. The eight linear and two angular measurements in the McNamara analysis were measured on images of the scanned radiographs. Measurements of the male and female subjects were compared with each other and with published norms for North American adolescents and adults. RESULTS: The Co-Gn, Co-A, ANS-Me and Ui-A were larger in the male subjects. Comparisons between the present study and McNamara's original study revealed that Anatolian Turkish adolescents, particularly girls, have smaller midfacial and mandibular lengths and longer and more retrusive faces than North American adolescents and adults. CONCLUSIONS: The small, but statistically significant, gender differences in mandibular and midfacial lengths and lower anterior face height may not be clinically significant. A single set of Turkish norms for the McNamara analysis may be appropriate. PMID- 20575198 TI - Assessment of slot sizes in self-ligating brackets using electron microscopy. AB - OBJECTIVE: To measure the slot dimensions of 0.022 inch self-ligating upper central incisor brackets from six manufacturers using electron microscopy, to compare the measured dimensions with the manufacturers' published dimensions, and to determine if the walls of the slots were parallel. MATERIALS: Six self ligating upper central incisor brackets from four manufacturers (SmartClip and Clarity SL, 3M Unitek, Monrovia, CA, USA; Speed, Strite Industries Ontario, Canada; Damon MX, Ormco, Orange, CA, USA; In-Ovation R and In-Ovation C, Dentsply GAC, Bohemia NY, USA) were imaged with a scanning electron microscope and the slots heights measured. Intra-operator repeatability and accuracy were determined. RESULTS: All brackets had slot sizes that were significantly larger (p < 0.05) than the stated 0.022 inch. Speed brackets were 5.1 per cent larger (0.02311 inch) and the closest to the published dimension. The SmartClip brackets were 14.8 per cent larger (0.02526 inch) than the quoted slot size of 0.022 inch. In most brackets the distances between the slot walls was generally greater further from the bracket bases. CONCLUSIONS: The actual measurements of upper central incisor self-ligating brackets from six manufacturers were larger than the manufacturers' stated dimension, and the walls of the slots diverged from the bracket bases. PMID- 20575199 TI - Space planning sensitivity and specificity: Royal London Space Planning and Korkhaus Analyses. AB - OBJECTIVES: To establish the sensitivity and specificity of the Korkhaus and Royal London Space Planning Analyses. METHODS: The sample consisted of 30 cases with two sets of study models and lateral cephalometric radiographs taken at least three years apart. These were then further subdivided into Class I (N = 10), Class II division 1 (N = 10) and Class II division 2 cases (N = 10). The Royal London Space Planning Analysis and the Korkhaus Analysis were applied on these cases at both times. RESULTS: Study model analysis: The Royal London Planning Analysis revealed that in Class I malocclusions, upper and lower arch crowding and spacing changed significantly with time. The total space required and tooth size reduction for the lower arch had also changed significantly. Additionally, in the Class II division 1 malocclusions, lower arch crowding and spacing, total space required and the need for tooth size reduction had significantly increased, while in Class II division 2 malocclusions, a statistically significant increase was observed in the upper and lower arch crowding and spacing. The Korkhaus Analysis showed that in Class I malocclusions, a significant decrease was observed in the lower arch length and the lower anterior arch width. The upper posterior (inter-molar) arch width had significantly increased. In Class II division 1 malocclusions the lower right posterior space available had decreased significantly. The upper posterior arch width and the lower posterior arch width also significantly increased. In Class II division 2 malocclusions, a statistically significant decrease was observed in the lower anterior arch length. There were no significant changes in all angular and the two linear measurements for all classes. CONCLUSIONS: The Royal London Space Planning Analysis and the Korkhause Analysis are clinically sensitive analyses. The Royal London Space Planning Analysis lacks specificity to be a robust model for treatment planning; modification may be required before this technique is accepted. PMID- 20575200 TI - Response of the expanded inter-premaxillary suture to intermittent compression. Early bone changes. AB - OBJECTIVE: To determine the response of the expanded premaxillary suture in the rat to an externally applied force. Specifically, to investigate early bone changes in the expanded suture to intermittent loading and unloading. METHODS: Twenty-four 50 to 60 day-old Wistar rats were assigned to three groups. The inter premaxillary sutures in all animals were expanded with a 50 g force applied to the upper incisors. Group I served as the control, whereas in Groups II and III the incisors were subjected to intermittent loading and unloading after five days of expansion. The intermittent forces were produced by a cam (0.416 mm, 100 cycles per minute) applied to the disto-gingival margins of the upper incisors. The mechanical stimuli were applied daily over nine days for six seconds in Group II (30 grams force, 10 cycles/day) and 10 minutes in Group III (30 grams force, 1000 cycles/day). Bone regeneration in the suture was evaluated histomorphometrically. The area of new bone (microm2), the perimeter around the new bone (microm), Feret's diameter (microm) and the percentage of new bone to non-ossified tissue (%) were measured and compared. RESULTS: Statistically significant differences were found between the groups for all histomorphometric parameters. New bone area (p < 0.001), bone perimeter (p < 0.001), Feret's diameter (p < 0.001) and percentage of new bone (p < 0.001) were significantly larger in the experimental groups as compared with the Control group. The histomorphometric measurements confirmed that more new bone was deposited in the sutures subjected to intermittent loading and unloading. CONCLUSION: The application of cyclic loading and unloading to the orthopaedically expanded inter premaxillary suture during the early retention phase stimulated the formation of new bone. PMID- 20575201 TI - Associations between upper lip activity and incisor position. AB - BACKGROUND: Muscle activity in the upper lip may influence the positions of the upper and lower incisors. OBJECTIVE: To determine the associations between muscle activity in the upper lip and the inclinations of the incisors, overjet and overbite. METHODS: Forty-five subjects (29 girls, 16 boys), between 11 and 15 years of age with predominantly Class I malocclusion, were used. The inclinations of the incisors, overjet and overbite were measured on lateral cephalometric radiographs. Bipolar electrodes were placed on the upper lip to record the activity in orbicularis oris muscle at rest, during maximal clenching, chewing hazelnuts and swallowing. Correlation coefficients between the cephalometric variables and the electromyographic (EMG) activity in the upper lip were calculated. RESULTS: There was no gender difference in the EMG activity in the upper lip. There were no statistically significant associations between the EMG activities in the upper lip and the inclinations of the incisors, overjet and overbite. CONCLUSIONS: The positions of the incisors do not appear to be influenced by muscle activity in the upper lip. PMID- 20575202 TI - Effects of levelling of the curve of Spee on the proclination of mandibular incisors and expansion of dental arches: a prospective clinical trial. AB - OBJECTIVES: To investigate the effects of levelling the curve of Spee (COS) on the inclination of the mandibular incisors and the width of the mandibular arch. METHODS: Fifty patients, 10-18 years of age, were selected using the following inclusion criteria: nonextraction treatment in the mandibular arch; eruption of all mandibular teeth; no spaces in the mandibular arch; no crowding in the posterior mandibular segments; a mandibular irregularity index greater than 2.5. The depth of the COS, the amount of crowding of the mandibular anterior dentition and the intercanine and intermolar widths were measured on standardised photographs of the casts. The inclinations of the mandibular incisors were measured on cephalometric radiographs. The paired t-test was used to analyse changes in the intercanine and intermolar widths and incisor inclinations before and after treatment, whilst the Wilcoxon signed ranks test was used to examine changes in the COS with treatment. The data were further analysed with a regression analysis to determine the measurements that predicted a reduction of the curve of Spee at the 5 per cent level of significance. RESULTS: The COS showed a median decrease of 0.9 mm, with 50 per cent of the cases ranging between 0.4 mm and 1.4 mm. The sole predictor of curve flattening was the lower incisor to mandibular plane angle. CONCLUSIONS: The COS is mainly 'flattened' by proclining the mandibular incisors. For 1 mm of levelling the mandibular incisors were proclined 4 degrees, without increasing arch width. PMID- 20575203 TI - A comparison of dental changes produced by mandibular advancement splints in the management of obstructive sleep apnoea. AB - BACKGROUND: Mandibular advancement splints (MAS) are a recognised and popular treatment option for obstructive sleep apnoea (OSA) due to their simplicity, tolerance and non-invasiveness. OBJECTIVES: To investigate and compare the dental changes associated with the use of monoblock and duoblock appliances. METHODS: Fifty-two pretreatment and follow-up study models of patients from a public hospital and private dental clinic were assessed. Seventeen subjects used a soft elastomeric monoblock appliance (MB), 29 subjects used a hard acrylic duoblock (DB) and six subjects wore a monoblock followed by a duoblock appliance (MB-DB). Measurements of dental and arch changes were obtained and analysed on study models and standardised bitewing radiographs. RESULTS: A statistically significant reduction was observed in the maxillary intercanine distance in all splint categories, with DB users showing the greatest decrease (p < 0.05). The change in the mandibular intercanine distances differed according to splint categories (p < 0.05). MB and MB-DB patients demonstrated a decrease in this measurement variable, whereas an increase was seen in DB users. A statistically significant increase in the mandibular intermolar distance was also observed in all splint categories (p < 0.05), with DB users showing the greatest increase. CONCLUSIONS: Both MB and DB appliance systems produced similar, but mild dental effects. No particular appliance can be recommended and the choice of appliance should be considered on a case-by-case basis. PMID- 20575204 TI - Does ozone water affect the bond strengths of orthodontic brackets? AB - BACKGROUND: Ozone water can be used to eliminate micro-organisms from the water systems in dental offices. OBJECTIVES: To determine if ozone water diminishes the bond strength of orthodontic adhesives. METHODS: One hundred and twenty bovine mandibular incisors were randomly divided into four equal groups. The teeth were cleaned with pumice and washed either with tap water (Groups 1 and 3) or with ozone water Groups (2 and 4) before bonding stainless steel orthodontics brackets to the teeth with either a composite resin (Groups 1 and 2; Transbond XT, 3M Unitek, Monrovia, CA, USA) or a resin-modified glass ionomer cement (Groups 3 and 4; Fuji Ortho LC, GC America Corporation, Tokyo, Japan). The manufacturers' recommendations for bonding were followed. All samples were subjected to thermal cycling and the shear bond strengths were determined with a universal testing machine. The Adhesive Remnant Index (ARI) was used to score the amount of resin remaining on the teeth after debonding the brackets. RESULTS: There were no statistical differences in the shear bond strengths of the brackets debonded from enamel washed with either ozone water or tap water or between the groups bonded with the two adhesive resins (p = 0.595). The ARIs in Groups 2 and 3 were significantly different from the ARIs in Groups 3 and 4 (p = 0.030). CONCLUSION: Ozone water did not alter the bond strength of brackets bonded with composite resins, but it did alter the sites of resin fracture when Fuji Ortho LC was used. PMID- 20575205 TI - Incremental effects of facemask therapy associated with intermaxillary mechanics. AB - OBJECTIVES: To determine the dentofacial changes in children with skeletal Class III malocclusions treated with maxillary expansion, external maxillary protraction and intermaxillary traction. METHODS: Fifteen Class III patients in either the deciduous or the mixed dentition (Mean age: 7.6 years; SD: 1.9 years) were used. The children were treated with a modified Haas expander, a modified lingual arch, intermaxillary elastics and facemask for nine months. Lateral cephalometric radiographs were taken at the beginning of treatment (T1) and at 3 month intervals (T2, T3, T4). RESULTS: Most significant sagittal skeletal modifications occurred in the first three months of treatment. During the first three months of treatment the upper and lower incisors tipped lingually and the face height increased. Towards the end of treatment the upper incisors proclined and the upper lip became more protrusive. CONCLUSION: The therapy corrected the horizontal skeletal and arch discrepancies and improved the positions of the lips. PMID- 20575207 TI - Multidisciplinary treatment of a fractured root: a case report. AB - AIM: To describe the orthodontic, periodontal and prosthetic management of a case with a 3 mm root fracture below the crest of the alveolar bone. METHODS: The root was extruded and periodontal surgery carried out to improve aesthetics and dental function. CONCLUSION: A multidisciplinary approach to the management of dental root fractures is necessary for successful treatment. PMID- 20575208 TI - Can an optimal force be estimated? PMID- 20575206 TI - Bond strengths of different orthodontic adhesives after enamel conditioning with the same self-etching primer. AB - AIM: To determine the shear bond strengths (SBS) of stainless steel brackets bonded with seven light-cured orthodontic adhesives after the enamel was conditioned with the same self-etching primer. METHODS: A total of 140 extracted human molars were randomly divided into seven groups (N = 20). In all the groups, the enamel was conditioned with Transbond Plus SEP (TPSEP). Stainless steel brackets were bonded with the following orthodontic adhesives: Group I, Transbond XT; Group II, Blugloo; Group III, BeautyOrtho Bond; Group IV, Enlight; Group V, Light Bond; Group VI, Transbond CC; Group VII, Xeno Ortho. The teeth were stored in distilled water at 37 degrees C for 24 hours and debonded with a universal testing machine. The modified adhesive remnant index (ARI) was also recorded. RESULTS: There were no significant differences in the SBS values among the groups: I (18.0 +/- 7.4 MPa); II (18.3 +/- 5.1 MPa); III (14.8 +/- 4.3 MPa); IV (18.3 +/- 7.0 MPa); V (16.4 +/- 4.3 MPa); VI (20.3 +/- 5.3 MPa); VII (15.9 +/- 6.4 MPa), but significant differences in ARI were found. CONCLUSIONS: The seven orthodontic adhesives evaluated in this study can be successfully used for bonding stainless steel brackets when the enamel is conditioned with TPSEP, however, the differences among some groups might influence the clinical bond strengths. In addition, the amount of residual adhesive remaining on the teeth after debonding differed among the adhesives. Further studies are required to better understand the differences in SBS and ARI. PMID- 20575210 TI - Breaking the silence barrier: opportunities to address breast cancer in African born women. AB - Women from Africa are a fast-growing population group in the United States; however, little is known about their breast cancer outcomes. There is minimal empirical data that describe the cancer practices, beliefs, and needs of African born women. We conducted 2 focus groups with 20 African women to: (1) explore their knowledge and attitudes about breast cancer practices and (2) identify potential intervention targets. Women were primarily from the western region of Africa (e.g., Nigeria, Ivory Coast), but there were representatives from the southern (e.g., Zimbabwe) and eastern (e.g., Ethiopia) regions as well. Their ages ranged from 21 to 60 years. Insurance coverage varied; 5 were uninsured. Findings indicated that women's knowledge and exposure to breast cancer prevention and screening were limited, and common explanations for breast cancer were that it is a boil or is a punishment from God. Barriers included limited knowledge, lack of insurance, spiritual beliefs, and secrecy. Suggestions for promoting breast health in this community included using culturally relevant materials and involving African men. Findings from this descriptive study provide useful insight to begin to understand the breast health experiences of African immigrant women. Additional research will be useful in developing culturally tailored breast cancer interventions. PMID- 20575209 TI - Mammography screening trends: the perspective of African American women born pre/post World War II. AB - Researchers have traditionally combined aging women (aged > or =50 years) when reporting their mammography use. This may inadvertently mask important cohort effects in mammography use, which are likely to result from distinct personal life experiences and generational differences. Using the Health and Retirement Study samples of 1998, 2000, and 2004, we examined cohort differences in mammography use between African American women born before 1946 (non-baby boomers) and those born in 1946 to 1953 (baby boomers). Between 1998 and 2004, screening rates for non-baby boomers declined, while those for baby boomers remained relatively steady. Hierarchical linear modeling (HLM) analyses suggest that while screening rates decreased with age (OR, 0.957; 95% CI, 0.947-0.968) cohort effects may have partially reversed the age effect, with non-baby boomers having an increased likelihood of receiving a mammogram compared to baby boomers (OR, 1.697; 95% CI, 1.278-2.254). Because African American women are diagnosed at later stages of breast cancer, documentation of cohort differences in mammography use among older African American women is important as health care professionals design intervention programs that are maximally effective for women from different cohorts. This is particularly critical as more African American women in the baby boomer cohort become part of the aging population. PMID- 20575211 TI - Self-reported weight loss practices among African American and Hispanic adults in the United States. AB - OBJECTIVE: To describe weight loss methods used and interactions with health care professionals on the issue of weight among African Americans and Hispanics. METHODS: Five hundred thirty-seven African American and 526 Hispanic adults who self-described as being overweight participated in a telephone interview. RESULTS: Exercise and healthy eating were the 2 most commonly used weight loss methods among both groups; prescription medications were the least-utilized weight loss aid. Forty-one percent of African Americans and 35% of Hispanics reported having been advised to lose weight by a health care professional. CONCLUSIONS: Do-it-yourself approaches to weight loss predominate among African Americans and Hispanics; formal assistance is rarely used. Physician advice on weight loss is suboptimal. PMID- 20575212 TI - Preferences for labor and delivery practices between pregnant immigrants and U.S. born patients: a comparative prospective antenatal survey study. AB - OBJECTIVE: To compare preferences in pregnant Somali and Sudanese immigrants with US-born women for different labor and delivery procedures and practices. STUDY DESIGN: Pregnant women who received prenatal care services at the Jericho Road Family Practice were surveyed. Ninety-three consecutive patients agreed to participate. A translator-facilitated questionnaire was administered to Somali-, Sudanese-, and U.S.-born women during antenatal visits. RESULTS: For pain relief in labor, 66.7% of U.S.-born, 64.0% of Somali, and 12.5% of Sudanese women preferred epidural analgesia (p = .002). More U.S.-born women preferred for the umbilical cord to be cut by their partners (76.2%) vs. Somali (6.7%) and Sudanese (0%) (p < .001). For infant feeding, more U.S.-born women (47%) preferred only formula feeding (Somali, 3.4%; Sudanese, 0%; p < .001). Responses were not statistically different for other preference questions, such as mobility/position in labor, attendants in labor, and duration of hospital stay. CONCLUSIONS: This prospective survey quantifies the differences in preferences for labor and delivery practices from two foreign populations and from U.S.-born women. This information is useful for all physicians who wish to better meet the needs of individual patients, especially those who are from different cultures and backgrounds. PMID- 20575213 TI - Vitamin D status of seminomadic Fulani men and women. AB - The purpose of this study was to assess the vitamin D status of Fulani men and women in northern Nigeria. The Fulani are seminomadic pastoralists whose culture, economy, and diet are centered on cattle. Most of the foods consumed by the Fulani are not good sources of vitamin D. Also being Muslim, the women do not derive much benefit from the vitamin D-generating effects of sunlight due to their dress habits. Furthermore, childhood rickets is common in the region. Serum was collected from 22 Fulani men (age, 47.6 +/- 8.3 years; body mass index [BMI], 21.1 +/- 3.2 kg/m2) and 29 women (age, 55.5 +/- 13.5 years; BMI, 21.6 +/- 3.1 kg/m2) in rural northern Nigeria and analyzed for 25-hydroxyvitamin D2 and D3 using ultraperformance liquid chromatography coupled with mass spectrometry Eighty-three percent of the women and 45% of the men had serum 25-hydroxyvitamin D levels in the hypovitaminosis D range (10-30 ng/mL). In the males, there was a strong negative correlation between serum vitamin D and BMI (r = -0.49, p = .022) and percent body fat (r = -0.51, p = .015). No such correlations were observed in the Fulani women. Our main conclusion is that about half the men and most of the women in the Fulani community where this study was conducted are inadequately nourished with respect to vitamin D. A high prevalence of hypovitaminosis D indicates an elevated risk for rickets in children and bone fractures in adults. PMID- 20575214 TI - Healthy competition: getting the best hospital care for patients. PMID- 20575215 TI - Race and HIV clinical trial participation. AB - PURPOSE: This study was designed to examine at the role race/ethnicity plays in human immunodeficiency virus (HIV) clinical trial enrollment. BACKGROUND: HIV clinical trials are vitally important for improving knowledge about medications and their impact on the pathogenesis of HIV/AIDS. African Americans are disproportionately underrepresented in HIV clinical trials. METHODS: A 49-item survey was administered to 145 patients at an urban HIV clinic to explore race and HIV clinical trial participation. RESULTS: Study participants were 56% Caucasian, 19% other, 16% African American, and 13% Hispanic. Fewer African Americans had been asked to participate in a trial compared to other groups (8% vs. 24%) (p < .05). African Americans were less likely to volunteer for a trial compared to Hispanics and Caucasians, but African Americans did not differ significantly in their willingness participate in clinical trials vs. other racial groups. In a regression model age, past trial participation, monetary gain, and comfort with the clinical setting predicted willingness to participate in a trial across racial groups (p < .05). DISCUSSION: There is a strong need to identify strategies to increase African American enrollment in trials. Such strategies need to begin with trial recruiters actively seeking out African Americans for clinical trial enrollment. PMID- 20575216 TI - A review of low-dose-rate prostate brachytherapy--techniques and outcomes. AB - Prostate cancer is the most common male cancer in the United States and the second leading cause of male cancer death. The main therapeutic modalities for the treatment of prostate cancer are surgery, external beam radiation therapy, hormonal therapy, and brachytherapy. In recent years, brachytherapy has been increasingly utilized for the treatment of early-stage prostate cancer. Technological advances, including improvements in imaging, planning, and postimplant quality assessment by dosimetry have led to widespread use of brachytherapy. Outcomes for prostate brachytherapy have been shown to be equivalent, in selected patients, to those of other treatment modalities for prostate cancer, including radical prostatectomy and external beam radiation therapy. Further, prostate brachytherapy has quality-of-life benefits in comparison to these other treatment modalities, particularly in the domain of sexual function. This paper describes the history of low-dose rate brachytherapy; current techniques for brachytherapy implantation and postoperative dosimetric evaluation; recent outcomes studies; recent quality-of-life analyses; and current and future prostate brachytherapy developments, including open clinical trials. As research in prostate brachytherapy continues, it is likely that this modality will play an increasingly important role in the treatment of early-stage prostate cancer patients in the future. PMID- 20575217 TI - Can therapies that target the incretin system improve our ability to treat type 2 diabetes? AB - Type 2 diabetes poses a major health challenge among African Americans. Older therapies are associated with shortcomings such as hypoglycemia and/or weight gain. In recent years the "incretin system" has become understood as offering great promise for drug development. Two drug classes-namely, the injectable glucagon-like peptide 1 (GLP-1) receptor agonists, which produce pharmacological GLP receptor activity, and the oral dipeptidyl peptidase-4 (DPP-4) inhibitors, which raise levels of endogenously produced GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) by preventing enzymatic degradation--have been available for several years. These drugs can be given as monotherapy or added to other antidiabetic drugs to lower blood glucose with very low risk of hypoglycemia without weight gain. In fact, GLP-1 receptor agonists may induce clinically significant reductions in weight and systolic blood pressure, as well as improve indices of beta-cell function. Although transient nausea occurs in some patients with GLP-1 receptor agonists, these agents are generally well tolerated, and the available clinical data are encouraging. Clinical experience shows that these treatments are acceptable to patients. PMID- 20575218 TI - A woman post mastectomy and radiation therapy with chest pain. PMID- 20575219 TI - ACE inhibitor-induced angioedema in elderly African American females requiring tracheostomy. AB - Angioedema is a well-demarcated localized edema involving the deeper layers of the skin, subcutaneous tissue, mucosa, and submucosa. It is a well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitor therapy. Prolonged angioedema is rare. In most cases, the angioedema is self-limited and responds to cessation of ACE inhibitor therapy. ACE inhibitor-related angioedema occurs more commonly in African American patients and tends to be particularly severe in elderly African American women. We report 2 cases of extremely severe angioedema of prolonged duration that required tracheostomy to stabilize the airway. PMID- 20575221 TI - Innovation expedition. As the CMS gears up its new laboratory for payment and quality control, excitement is mixed with anxiety. AB - As the CMS prepares to launch its center for innovation, there's both excitement and apprehension. The center holds the promise of crafting bold improvements for payment systems and quality of care. "As long as there is the promise of long term cost savings and quality improvement, they have the authority to say, 'We found something that works and we want to do it more broadly,' "says Stuart Guterman, left, of the Commonwealth Fund. PMID- 20575220 TI - Gone (from the Physicians' desk reference) but not forgotten: propylthiouracil associated hepatic failure: a call for liver test monitoring. AB - A 19-year-old female diagnosed with Graves' disease had treatment initiated with propylthiouracil (PTU). Pretreatment complete blood count and liver-associated enzymes (LAEs) were normal, but no further LAEs were obtained, reflecting U.S. guidelines written in 1995. Three months later, she presented with nausea, vomiting, abdominal pain, and jaundice. LAEs were markedly elevated with: total bilirubin, 6.5 mg/dl; aspartate aminotransferase (AST), 1747 IU/L; and alanine aminotransferase (ALT) 1589 UL/L. After 6 days at an outside hospital, she was transferred to our tertiary care center in acute liver failure with coagulopathy and stage II encephalopathy. Liver transplant evaluation was promptly initiated and she was listed as status 1. PTU was the only medication she had taken; and all serologic, autoimmune, and metabolic studies were negative. She demonstrated rapid clinical deterioration, and on hospital day 7 she underwent orthotopic liver transplant but succumbed to tonsillar herniation immediately after surgery. Pathology from her explanted liver revealed marked necrosis and collapse, consistent with her acute liver failure. PTU-associated hepatotoxicity and myelotoxicity have been well-recognized serious adverse effects for more than 50 years. However, as deaths related to hepatic injury from PTU are rare, American Thyroid Association guidelines do not call for routine monitoring of LAEs, although monitoring of white blood cell count levels is advised. Given the wide spectrum of PTU-related liver injury, ranging from asymptomatic elevations in ALT to fatal acute liver failure, we urge consideration of an LAE monitoring program to prevent irreversible liver damage and call for a reappraisal of monitoring guidelines in the United States. PMID- 20575222 TI - Checking the levels. Providers applaud safety checks in radiation equipment, hope for more. PMID- 20575223 TI - Prescription for invention. Product incubators help physician entrepreneurs bring their innovative ideas to market. PMID- 20575224 TI - Extending a hand. Regional centers to offer guidance on IT issues. PMID- 20575225 TI - Pharmaceutical markets and insurance worldwide. Overview. PMID- 20575226 TI - Pharmaceutical policies in European countries. AB - PURPOSE: Pharmaceutical expenditures have an important role in Europe. The attempts to control expenditure have used a wide range of policy measures. We reviewed the main measures adopted by the European Union countries, especially in countries where governments are the largest third-party payers. METHODOLOGY: To complement a literature review on the topic, data was gathered from national reviews of health systems and direct inquiries to several government bodies. FINDINGS: Almost all countries regulate prices of pharmaceutical products. Popular policy measures include international referencing to set prices (using as benchmark countries that have set lower prices), internal reference pricing systems to promote price competition in domestic markets, and positive lists for reimbursement to promote consumption of generics (including in some cases substitution by pharmacists of drugs prescribed by physicians). Despite the wide range of policy measures, it is not possible to identify a "silver bullet" to control pharmaceutical expenditures. We also identified two main policy challenges: policy coordination among countries within the European Union to maintain incentives for R&D at the global level, and the development of new relationships with the pharmaceutical industry; namely, the so-called risk sharing agreements between the pharmaceutical industry and governments/regulators (or large third-party payers). PMID- 20575227 TI - International experience with comparative effectiveness research: case studies from England/Wales and Germany. AB - PURPOSE: Although the US has lagged behind international developments in health technology assessment (HTA), renewed interest in HTA in the US has been fueled by the appropriation of $1.1 billion comparative effectiveness research (CER) in 2009 and the debate over health care reform. APPROACH: To inform CER practices in the US, we present case studies of HTA from England/Wales and Germany: contrasting methods; relevance to the US; and impact on innovation. FINDINGS: The National Institute of Health and Clinical Excellence (NICE) was established in 1999 to inform trusts within the National Health Service of England and Wales. It uses cost-effectiveness analysis to guide the allocation resource across preventative and curative interventions. In Germany, the Institut fur Qualitat und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) was established in 2004 to inform reimbursement and pricing policies for the statutory sickness funds set by the Gemeinsamer Bundesaursschuss (G-BA). IQWiG evaluates competing technologies within specific therapeutic areas, placing more weight on clinical evidence and the relative efficiency of competing therapies. PRACTICAL IMPLICATIONS: Although having deep political and cultural antecedents, differences between NICE and IQWiG can be explained by perspective: the former guiding resource allocation across an entire system (macro-evaluation), the latter focusing on efficiency within the bounds of a particular therapeutic area (micro-evaluation). Given the decentralized nature of the US health care system, and the relative powers of different medical specialties, the IQWiG model presents a more suitable case study to guided CER efforts in the US. PMID- 20575228 TI - Pharmaceutical policy in the Netherlands: from price regulation towards managed competition. AB - PURPOSE: To analyse the development of pharmaceutical policy in the Dutch market for outpatient prescription drugs since the early 1990s. METHODOLOGY: A literature review and document analysis is performed to examine the effects of pharmaceutical policy on the performance of the Dutch market for outpatient prescription drugs since the early 1990s. FINDINGS: Government efforts to control prices of pharmaceuticals were effective in constraining prices of in-patent drugs, but had an opposite effect on the prices of generic drugs. The gradual transition towards managed competition--that particularly gained momentum after the introduction of the new universal health insurance scheme in 2006--appears to be more effective in constraining prices of generic drugs than earlier government efforts to control these prices. ORIGINALITY: Comparative analysis of the impact of price regulation and managed competition on generic drug prices in the Netherlands. IMPLICATIONS: Implications of the changing role of health insurers are discussed for the future market for prescription drugs and role of pharmacies in the Netherlands. PMID- 20575229 TI - Impact of pharmaceutical regulation and policies on health system performance goals in Israel. AB - PURPOSE: There is a particular need for health policy evaluations in terms of achievement of goals, which may help inform policy-making not only locally but for the wider international policy community. In this chapter, we review the impact of pharmaceutical regulation and policies in Israel on a range of health system performance goals that, in the pharmaceutical context, are mainly related to ensuring the availability, accessibility and affordability of medicines. APPROACH: We assess pharmaceutical policies and their impact, within the Israeli National Health Insurance (NHI) system enacted in 1995, on the degree to which the following main policy goals are being achieved: containment of drug expenditures; sustainability and equity of financing for pharmaceuticals; efficiency of expenditure in the pharmaceutical sector; and availability and accessibility of pharmaceuticals. FINDINGS: The findings point to a number of accomplishments as well as outstanding challenges. The main accomplishment is successful cost containment of (public) expenditure on medicines. Government price regulation operates as a mechanism responsible for sickness funds' (SFs) savings, over which the state has no information or monitoring. Although the package of publicly financed drugs is comprehensive, delays in reimbursement decisions and high level of cost sharing mean that medicines have become increasingly unaffordable for many patients, especially for low-income persons with chronic diseases. IMPLICATIONS: Regulation of the pharmaceutical sector should focus on two aspects: decreasing the information gap between the SFs and the regulator and reforming the cost-sharing policy to increase affordability and equity. PMID- 20575230 TI - Global budgets and provider incentives: hospitals' drug expenditures in Taiwan. AB - PURPOSE: This chapter examines how drug prescribing behavior in Taiwanese hospitals changed after the government changed reimbursement systems. In 2002, Taiwan instituted a system in which hospitals are reimbursed for drug expenditures at full price from a fixed global budget before the remaining budget is allocated to reimburse all other expenditures, often at discounted prices. Providers are thus given a financial incentive to increase prescriptions. METHODOLOGY: We isolate the effect of this system from that of other confounding factors by estimating a difference-in-difference model to analyze monthly drug expenditures of hospital departments for outpatients during the years 1999-2006. FINDINGS: Our results suggest that hospital departments which use drugs more heavily as part of their regular medical care increased their drug prescription expenditures after the implementation of the global budget system. In addition, we find that the response was stronger among for-profit than not-for-profit and public hospitals. IMPLICATIONS: Hospital doctors responded to the financial incentive created by the particular global budgeting system adopted in Taiwan by increasing expenditures on drug treatments for outpatients. PMID- 20575231 TI - Medicare Part D turns four: trends in plan design, enrollment, and the impact of the program on beneficiaries. AB - PURPOSE: As Medicare Part D enters its fifth year, we assess how the supply side of the market has evolved and what research has shown about how Medicare drug coverage has affected consumers. METHODS: We conduct descriptive data analyses to explore the varied nature of Medicare standalone prescription drug plans (in terms of both price and non-price features), examine features associated with high enrollment, and show trends over time in both plan design and enrollment patterns from 2006 to 2010. We also review existing evidence about Part D's effects on drug access for beneficiaries and conclude with a discussion of current policy concerns. FINDINGS: Medicare Part D has been successful in certain ways, but several areas of concern remain. Although it is a measure of success that 90% of Medicare beneficiaries now have drug coverage, efforts continue to reach the vulnerable populations who are not yet signed up. Use of medications (and relative use of generics) has increased under the program, while out of pocket costs have fallen. Policymakers continue to question government's role in areas such as negotiating prices directly with pharmaceutical manufacturers and limiting the number of plans offered. Results from data analysis indicate, among other things, high growth in premiums, whereas plans have become less generous by certain measures. ORIGINALITY: This chapter brings together data on all plans offered in Medicare Part D standalone drug coverage market and shows new evidence on the landscape's rapid evolution. PMID- 20575232 TI - Does prescription drug adherence reduce hospitalizations and costs? The case of diabetes. AB - PURPOSE: To estimate the impact of diabetic drug adherence on hospitalizations, emergency room (ER) visits, and hospital costs. METHODS: It is often difficult to measure the impact of drug adherence on hospitalizations since both adherence and hospitalizations may be correlated with unobservable patient severity. We control for such unobservables using propensity score methods and instrumental variables for adherence such as drug coinsurance levels and direct-to-consumer advertising. FINDINGS: We find a significant bias due to unobservable severity in that patients with more severe health are more apt to comply with medications. Thus, the relationship between adherence and hospitalization will be underestimated if one does not control for unobservable severity. Overall, we find that increasing diabetic drug adherence from 50% to 100% reduces the hospitalization rate by 23.3% from 15% to 11.5%. ER visits reduce by 46.2% from 17.3% to 9.3%. Although such an increase in adherence increases diabetic drug spending by $776 a year per diabetic, the cost savings for averted hospitalizations and ER visits are $886 per diabetic, a cost offset of $1.14 per $1.00 spent on diabetic drugs. ORIGINALITY: Most of the drug cost-offset literature focuses only on the impact of cost-sharing and drug spending on cost-offsets, making it impossible to back out the empirical impact of actual drug adherence on cost-offsets. In this chapter, we estimate the direct impact of adherence on hospitalizations and costs. PMID- 20575233 TI - Cost sharing, benefit design, and adherence: the case of multiple sclerosis. AB - PURPOSE: The authors focus on understanding the relationship between costs and cost sharing on medication adherence for individuals who initiated a disease modifying therapy (DMT) for the treatment of multiple sclerosis (MS). DMTs reduce the risk of relapse and are an essential component of MS treatment. Furthermore, the authors compare monthly payment levels for copayments versus coinsurance and estimate the effects on adherence. METHODS: Using the MarketScan Commercial Claims and Encounters database evidence from July 1 2005 to March 31 2008, the authors employ a multivariate two-stage least-squares model (2SLS) to examine the impact of copayments or coinsurance on the medication possession ratio (MPR). FINDINGS: Descriptive results show that the mean out-of-pocket (OOP) costs of DMT per month were higher for patients with coinsurance than for patients with copayments. For the cohort of patients with copayment there was little difference in monthly copayments across adherence thresholds. Regression analysis shows that an increase in cost sharing reduces adherence overall, but this effect was small and insignificant in the copayment cohort. In contrast, in the coinsurance cohort increased cost sharing was significantly associated with decreased adherence to DMT medication; with a 10% increase in cost sharing leading to an 8.6% decline in adherence. IMPLICATIONS: Employers increasingly rely on coinsurance, despite evidence that reliance on coinsurance results in lower adherence. Our research findings suggest that coinsurance appears to be a greater obstacle to compliance, confirming predictions found in the theoretical literature. ORIGINALITY: This research converted counts of injectable treatments into a continuous adherence measure. Previous literature on cost sharing did not examine MS. PMID- 20575234 TI - Generic utilization and cost-sharing for prescription drugs. AB - PURPOSE: The purpose of this study is to estimate the own- and cross-price elasticity of brand-name outpatient prescription drug cost-sharing for maintenance medications and to estimate the effects of changes in the price differential between generic and brand-name prescription drugs. METHODOLOGY/APPROACH: We first review the literature on the effects of an increase in brand-name drug patient cost-sharing. In addition, we analyze two examples of utilization patterns in filling behavior associated with an increase in brand-name cost-sharing for patients in employer-sponsored health plans with chronic illness. FINDINGS: We found that the own-price elasticity of demand for brand-name prescription drugs was inelastic. However, the cross-price elasticity was not consistent in sign, and utilization patterns for generic prescription fills did not always increase after a rise in brand-name cost-sharing. RESEARCH LIMITATIONS: The empirical examples are limited to the experience of patients with employer-sponsored health insurance. PRACTICAL IMPLICATIONS: The common practice of increasing brand-name prescription drug patient cost-sharing to increase consumption of generic drugs may not always result in higher generic medication use. Higher brand-name drug cost-sharing levels may result in discontinuation of chronic therapies, instead of therapeutic switching. ORIGINALITY/VALUE OF CHAPTER: The value of this chapter is its singular focus on the effects of higher brand-name drug cost-sharing through a synthesis of the literature examining the own- and cross-price elasticity of demand for brand-name medications and two empirical examples of the effects of changes in brand-name cost-sharing. PMID- 20575235 TI - Drug prices, out-of-pocket payments, and insurer costs: how do payers vary? AB - PURPOSE: To examine how drug prices for specific diseases vary across payers in the United States and how insurer and patient out-of-pocket (OOP) costs vary by payer type. METHODOLOGY: This study uses data from the Medical Expenditure Panel Survey (MEPS) from 1996 to 2006. We estimate multivariate price regressions for four major drug product classes (antihypertensive, antidepressant, antiasthma drugs, and non-steroidal anti-inflammatory drugs (NSAIDs)). Separate models are estimated for brand and generic drugs within each of these drug product classes. In addition to estimating overall transaction price equations for brands and generics, the study estimates patient OOP payments and insurer payments for drugs. FINDINGS: We find relatively modest differences among payers in terms of total prices (e.g., insurer plus OOP). The main difference is in terms of how prices were shared between insurers and patients. Medicaid paid significantly more than other payers for each drug class, while Medicaid beneficiaries paid significantly less. RESEARCH IMPLICATIONS: Our results shed light on how drug prices vary by different payers and how drug prices are shared by third party payers and patients. The relatively modest differences in total drug prices across payer type suggest that these payers do not differ greatly in terms of their ability to negotiate price concessions from their suppliers. Instead, larger differences emerge in terms of how total costs are shared among the payer and their patients. Understanding the reasons for these variations, and their implications for health outcomes, are important directions for further research. PMID- 20575236 TI - Adverse selection and the effect of health insurance on utilization of prescribed medicine among patients with chronic conditions. AB - PURPOSE: To examine the effects of health insurance types on the use of prescribed medication that treat patients with hypertension, diabetes, and asthma. The study distinguishes between individuals with private health maintenance organization (HMO) plans and private non-HMO plans. The study also distinguishes between people with health insurance and drug coverage and people with health insurance and no drug coverage. METHODS: Joint discrete factor models are estimated to control for endogeneity of each type of coverage. FINDINGS: The main findings suggest that the effect of health insurance varies across patients with different conditions. The strongest and most significant effect is evident among patients with hypertension while the weakest and least significant is among patients with asthma. These findings suggest that patients with asymptomatic conditions are more likely to exhibit moral hazard than patients with conditions that impose immediate impairment. Additional results suggest that, relative to the uninsured and people with health insurance but no drug coverage, patients with drug coverage are more likely to initiate drug therapy and to consume more medications. ORIGINALITY: The results of the study indicate that moral hazard of drug utilization is condition specific. The variation in "silence" of conditions' symptoms could be a key reason for difference in insurance effects among patients with hypertension, diabetes, and asthma. PMID- 20575237 TI - The effect of drug vintage on survival: micro evidence from Puerto Rico's Medicaid program. AB - Using micro data on virtually all of the drugs and diseases of over 500,000 people enrolled in Puerto Rico's Medicaid program, the impact of the vintage (original FDA approval year) of drugs used to treat a patient on the patient's three-year probability of survival, controlling for demographic characteristics (age, sex, and region), utilization of medical services, and the nature and complexity of illness are examined. It is found that people using newer drugs during January-June, 2000, were less likely to die by the end of 2002, conditional on the covariates. The estimated mortality rates are strictly declining with respect to drug vintage. For pre-1970 drugs, the estimated mortality rate is 4.4%. The mortality rates for 1970s, 1980s, and 1990s drugs are 3.6%, 3.0%, and 2.5%, respectively. The actual mortality rate is about 16% (3.7% vs. 4.4%) lower than it would have been if all of the drugs utilized in 2000 had been pre-1970 drugs. Estimates for subgroups of people with specific diseases display the same general pattern. PMID- 20575238 TI - Retail pharmacy market structure and insurer-independent pharmacy bargaining in the Medicare Part D era. AB - OBJECTIVE: To examine whether local area pharmacy market structure influences contract terms between prescription drug plans (PDPs) and pharmacies under Part D. DATA: Data were collected and compiled from four sources: a national mail survey to independent pharmacies, National Councilfor Prescription Drug Programs (NCPDP) Pharmacy database, 2000 U.S. Census data, and 2006 Economic Census data. RESULTS: Reimbursements varied substantially across pharmacies. Reimbursement for 20mg Lipitor (30 tablets) ranged from $62.40 to $154.80, and for 10mg Lisinopril (30 tablets), it ranged from $1.05 to $18. For brand-name drug Lipitor, local area pharmacy ownership concentration had a consistent positive effect on pharmacy bargaining power across model specifications (estimates between 0.084 and 0.097), while local area per capita income had a consistent negative effect on pharmacy bargaining power across specifications(-0.149 to -0.153). Few statistically significant relationships were found for generic drug Lisinopril. CONCLUSION: Significant variation exists in PDP reimbursement and pharmacy bargaining power with PDPs. Pharmacy bargaining power is negatively related to the competition level and the income level in the area. These relationships are stronger for brand name than for generics. As contract offers tend to be non negotiable, variation in reimbursements and pharmacy bargaining power reflect differences in initial insurer contract offerings. Such observations fit Rubinstein's subgame perfect equilibrium model. IMPLICATION: Our results suggest pharmacies at the most risk of closing due to low reimbursements are in areas with many competing pharmacies. This implies that closures related to Part D changes will have limited effect on Medicare beneficiaries' access to pharmacies. PMID- 20575239 TI - Patents, innovation, and the welfare effects of Medicare Part D. AB - PURPOSE: To evaluate the efficiency consequences of the Medicare Part D program. METHODS: We develop and empirically calibrate a simple theoretical model to examine the static and the dynamic welfare effects of Medicare Part D. FINDINGS: We show that Medicare Part D can simultaneously reduce static deadweight loss from monopoly pricing of drugs and improve incentives for innovation. We estimate that even after excluding the insurance value of the program, the welfare gain of Medicare Part D roughly equals its social costs. The program generates $5.11 billion of annual static deadweight loss reduction and at least $3.0 billion of annual value from extra innovation. IMPLICATIONS: Medicare Part D and other public prescription drug programs can be welfare-improving, even for risk-neutral and purely self-interested consumers. Furthermore, negotiation for lower branded drug prices may further increase the social return to the program. ORIGINALITY: This study demonstrates that pure efficiency motives, which do not even surface in the policy debate over Medicare Part D, can nearly justify the program on their own merits. PMID- 20575240 TI - [The patient must be at the center]. PMID- 20575241 TI - [Confused persons. In a nursing home at 30 years? ]. PMID- 20575242 TI - [Concerning confused persons. The burden should not become and abandonment]. PMID- 20575243 TI - ["Brain-injured people deserve place where the rhythms are applied"]. PMID- 20575244 TI - ["Overture." First communal meeting in the health professions]. PMID- 20575245 TI - [New competencies in health professions. Attractiveness rises with the value of the professions]. PMID- 20575246 TI - [Personnel recruitment. "Regional emergency" nursing]. PMID- 20575247 TI - ["Nurse Glaser certainly is not long-winded"]. PMID- 20575248 TI - [For the future more specializing and competence]. PMID- 20575249 TI - ["I have absolutely lost confidence in justice"]. PMID- 20575250 TI - [Consultation of patients with heart insufficiency. Self-management increases quality of life]. PMID- 20575251 TI - [A project concerning management of health promotion. Let the auxiliary nursing personnel be evaluated]. PMID- 20575252 TI - [Quarrels with interns. Retirement in anger against a new employment contract]. PMID- 20575253 TI - [State of emergency]. PMID- 20575254 TI - [Mission at the university hospital at Port-au-Prince. About nurses in the midst of distress]. PMID- 20575255 TI - [Endoscopy in nursing. I am here, I shall remain here!]. PMID- 20575256 TI - [Mobbing: painful and expensive]. PMID- 20575257 TI - [Individuality]. PMID- 20575258 TI - [Safety and immunogenicity of the diphtheria, tetanus, accellular pertussis plus hemophilus influenza type b combined vaccine (DTaP-Hib) to Chinese infants]. AB - OBJECTIVE: To evaluate the safety and immunogenicity of combined diphtheria, tetanus, accellular pertussis Plus hemophilus influenza type b vaccine (DTaP Hib)to Chinese infants. METHODS: Safety study (study A), and immunogenicity and safety study (study B) were conducted in infants aged 3, 4 and 5 months. The immune response and safety of the DTaP-Hib vaccine were compared after administered DTaP and Hib separately based on specified criteria. RESULTS: A total of 690 healthy infants received primary vaccination with combined DTaP-Hib or administered DTaP and Hib(DTaP+Hib) separately. Immunogenicity was assessed before and one month after vaccination in a subjet. The tolerance of DTaP-Hib vaccine was at least as same as administered DTaP+Hib separately. The differences of local and general adverse events following immunigation (AEFI) between groups had no difference statisticaly significantly. At least 97.5% of DTaP-Hib recipients had seroprotection against diphtheria, tetanus and Hib, and response to acellular pertussis antigens one month after primary vaccination. The immune response of the DTaP-Hib vaccine was comparable to administered DTaP+Hib based on specified criteria separately. CONCLUSION: The combined DTaP-Hib vaccine gets expected safety and immunogenicity. PMID- 20575259 TI - [Evaluation of real time fluorescent quantitative reverse transcription polymerase chain reaction for detection of poliovirus]. AB - OBJECTIVE: Application of Real Time Fluorescent quantitative reverse transcription polymerase chani reaction (rRT-PCR)to poliovirus identification in Chinese Poliomyelitis Laboratory Network and evaluation of the assay. METHODS: According to Real-time RT-PCR recommended by WHO and developed by USA Centers for Disease Control and Prevention, 10 poliovirus isolates from laboratories of Chinese poliomyelitis network were tested for intratypic differentiation (ITD) and vaccine derived polioviruses (VDPVs) screening. The results of Real-time RT PCR for 10 isolates were compared with those of VP, region sequencing. RESULT: The Real-time RT-PCR results for 10 isolates did not completely consist with those of VP1 region sequencing. 5 Pre-VDPVs can not be identified by Real-time RT PCR and type IVDPV from Shanxi province in 2009 was missed by the assay. CONCLUSION: The Real-time RT-PCR retrospective and prospective researches for large scale of polioviruses well be conducted to determine if the assay is applicable to Chinese Poliomyelitis Laboratory Network. PMID- 20575260 TI - [Evaluation on running status of Chinese Polio Laboratories Network in 2008]. AB - OBJECTIVE: In order to evaluate the running status and provide the laboratory data for maintaining polio-free status in China, the virology surveillance database of Chinese Polio Laboratories Network (not include Hong Kong, Macao, and Taiwan)in 2008 were analyzed. METHODS: The case investigation data of Acute Flaccid Paralysis(AFP)cases reported by 31 provinces (municipal, autonomous regions) through EPI surveillance information management system and the database of National Polio Laboratory (NPL) were analyzed, and the indicators of running status of Chinese Polio Laboratories Network were evaluated. RESULTS: 10,116 stool samples were collected from 5116 AFP cases by Chinese Polio Laboratories Network in 2008, and viral isolation and identification of all stool samples were done according to 4th World Health Organization (WHO) Polio Laboratory Manual. The rate of viral isolation and identification performed within 28d was 94.9%. 189 polioviruses (PV) and 597 of non-polio enteroviruses (NPEV) were isolated from AFP cases, the isolatien rates were 3.72% and 11.74% respectively. 251 polio positive isolates were sent to NPL from 31 provincial polio laboratories. There were 318 single serotype PVs were performed VPI sequencing. And no wild polioviruses and Vaccine-derived Polioviruses (VDPVs) were found in 2008. NPL passed the proficiency test and got full accreditation for on-site review by WHO experts in 2008. All 31 provincial Polio laboratories passed the proficiency test with the same panel as NPL, and 13 provincial Polio laboratories joined and passed the on-site review by WHO experts. CONCLUSION: The running status of Chinese Polio Laboratories Network was good, polio-free status was maintained in China in 2008. The Chinese polio laboratories network running is normaly, the laboratory surveillance system was sensitive and laboratory data were provided for maintaining the polio-free status in China. PMID- 20575261 TI - [Analysis on genetic characteristic of type I poliovirus in China in 2009]. AB - OBJECTIVE: To study the molecular characteristics of type 1 poliovirus isolated from the acute flaccid paralysis (AFP)surveillance system in China in 2009, to provide a scientific basis for maintaining polio-free status for China. METHOD: Polymerase chain reaction (RT-PCR) method was used to amplify the VP1 code region of all the type I poliovirus, and the VP1 coding region of the isolated stains was sequenced and analyzed, the hot-spots and nuerovirulence determinant were analyzed. The phylogenetic tree was constructed based on VP1 region to analyze the evolutionary relationship between the strains. RESULT: The results of VP1 sequencing showed that no wild strains or vaccine-derived poliovirus (VDPVs) were detected. However, five pre-VDPVs were found. And nucleotide sequences of two isolates were in high degree of similarity (100%). Sequence alignment showed that two nucleotides in the VP1 region. nt2747 and nt2749 were two mutation hot spots. CONCLUSION: According to the epidemiological and laboratory test results of two high variation strains, the short-term circulation may occur probably, and further research are needed. Meanwhile, the existence of mutation hot spots indicated that strains are easy to reverse into wild-type substitutions, and lead to a series changes of neurological and other virulence when the strains are under selective pressure. PMID- 20575262 TI - [Analysis on vaccine-derived poliovirus found from acute flaccid paralysis cases and effectiveness for emergency response in Binzhou in 2007]. AB - OBJECTIVE: To analyze VDPV found from acute flaccid paralysis cases and effectiveness for emergency response in Binzhou, Shandong in 2007. METHODS: Outbreak investigation, rapid evaluation for oral poliomyelitis attenuate live vaccine (OPV) coverage rate, active searched for acute flaccid paralysis (AFP)cases, supervision for VDPV case, virology and serology surveillance, mopping-up of OPV were used for this emergency response to prevent the possible VDPV spread. RESULTS: The case was reported from the AFP surveillance system. The poliovirus type I was isolated from stool specimen, which was identified as VDPV by gene sequencing. This AFP case was diagnosed as Guillain-barre syndrome (GBS) with 11 doses of OPV and normal self-immunity function test. The investigation results showed that the OPV coverage rates and the neutralization antibody to poliovirus type 1-3 were at high level among the local children, no similar VDPV was isolated from stools of healthy children around the case. The quality of AFP surveillance system was good, and had not found additional similar case in Bizhou city. Additional VDPV was not found in continuous stool specimen from this case. The case was diagnosed as VDPV infected vector but not VDPV case by the national and provincial expert group. CONCLUSION: This VDPV was found in the area with high coverage rate OPV, There was no evidence for the VDPV circulation. The emergency response for the VDPV was rapid and effective. The VDPV surveillance and research related should be strengthened. PMID- 20575263 TI - [Analysis of 4 clustered high risk acute flaccid paralysis cases in Shanxi Province in 2006]. AB - OBJECTIVE: Analysis of epidemiology of 4 clustered high risk acute flaccid paralysis(AFP) cases reported by Shanxi province in 2006 and VP1 gene characteristic for type III poliovirus isolated from the four AFP cases. METHODS: Virus isolation and identification were conducted according to the 4th edition of WHO polio laboratory manual. The sequence of VP1 region were amplified and sequenced. The phylogenetic trees based on VP1 region were constructed. RESULT: Three of four high risk AFP cases were suspected as vaccine associated paralysis poliomyelitis (VAPP), the onset date of them were close. VP1 sequencing of the four type III isolates revealed that the identity were 99.7%, 99.9%, 99.4% and 99.9% respectively compared with vaccine reference strain-BJOPV3. According to WHO criteria, the four isolates were identified as type III vaccine-related poliovirus. Phylogenetic analysis based on VP1 coding sequence showed that the four type III poliovirus were not related significantly. The type III poliovirus isolated from 3 suspected VAPP cases shared one nucleotide mutation at 2637 (C- >U), which result in the amino acid mutation from Val into Ala. CONCLUSION: The improvement of laboratory surveillance for clustered high risk AFP cases should be strengthened so as to detect and prevent poliovirus circulation timely. PMID- 20575264 TI - [Norovirus infection in adults with sporadic gastroenteritis during 2007-2008 in Nanning Municipal]. AB - OBJECTIVE: To investigate the epidemiological characteristic and genotype distribution of norovirus infection among adult patients with sporadic gastroenteritis in Nanning Municipal. METHODS: The epidemiological data of adult diarrhea patients in outpatient clinics of a hospital in Nanning City between January 2007 and December 2008 were analyzed. A total of 696 fecal specimens were collected from the patients and were screened for the presence of norovirus RNA by real-time reverse transcription-polymerase chain reaction. Some positive specimens were selected randomly and subjected for sequencing and phylogenetic analysis to identify genotypes. RESULTS: The sporadic norovirus infection in adults occurred preferentially during the cold season, and there was no statistical difference in the detection rate between age groups. 183 (26.30%) of 696 specimens were positive for norovirus RNA. Among them, 180 (98.36%) belonged to genogroup II (G II) and the other 3 (1.64%) belonged to genogroup I (G I). The sequence analysis showed that all 10 G II strains selected randomly belonged to genotype G II4, while 3 GI strains were classified into three different genotypes: G I2, G I4 and G I8. CONCLUSION: The study showed that norovirus was an important etiologic agent of sporadic gastroenteritis among adults in Nanning City. Genotype G II4 was the predominant genotype, and genotype GI existed sporadically. PMID- 20575265 TI - [Analysis on the effects of hepatitis B vaccine to prevent mother-to-children transmission of hepatitis B virus in Shunyi District of Beijing Municipal]. AB - OBJECTIVE: To evaluate the effects of immunization strategy about Hepatitis B vaccine preventing mother-to-children transmission (MTCT)of Hepatitis B virus (HBV) in Shun Yi District of Beijing. METHODS: The supervision data of blood serum of the children born from mothers who HBsAg carrier or HBsAg and HBeAg carrier were collected during the years of 2005-2008. The positive rate of HBsAg, anti-HBs, anti-HBc and the protective rate were analyzed. RESULTS: 223 children born from mothers of HBsAg and HBeAg carrier or HBsAg carrier were vaccinated according to the Hepatitis B vaccine immunigation strategy of Beijing. The infective rate of HBV was 1.18%, and protective rate of HepB was 98.61%. The infective rate of HBV of the children born from mothers of HBsAg and HBeAg carrier was higher than the rate of the children born from mothers of HBsAg carrier. The positive rate of anti-HBs was 84.71%. There were statistics significance in different years. The GMC of anti-HBs was 139.32 mIU per mL. The anti-HBs GMC of 2007 and 2008 were higher than those of 2005 and 2006. The anti HBs GMC of the children who HBIG adopted was higher than that of the children who HBIG did not adopted. CONCLUSION: The Hepatitis B vaccine immunization strategy of Shun Yi District had good immunological and protective effects to prevent HBV perinatal transmission. PMID- 20575266 TI - [Serum antibody response to different doses of hepatitis B vaccine made by recombinant DNA techniques in yeast and Hansenula polymorpha yeast]. AB - OBJECTIVE: To observe the serum antibody response of the population, whose hepatitis B virus surface antigen(HBsAg), antibody to hepatitis B virus surface antigen (Anti-HBs), antibody to hepatitis B virus core antigen (Anti-HBc) are all negative to the different doses of Hepatitis B vaccine made by recombinant DNA techniques in Yeast and Hansenula Polymorpha Yeast. METHODS: Collecting the blood of population vaccinated after 28 to 45 days, the serological method was used to detect Anti-HBs. RESULTS: The Anti-HBs positive rate and GMC of 5 microg HepB-Y in the population <16 years old whose HBsAg, Anti-HBs, Anti-HBc negative are 97.23% and 199.26 mlU/ml, the Anti-HBs positive rate and GMC of 10 microg HepB HPY are 100.00% and 270.71 mlU/ml, the Anti-HBs positive rate and GMC both have significant difference. The Anti-HBs positive rate and GMC of 10 microg HepB-Y in the population > or =16 years old whose HBsAg, Anti-HBs, Anti-HBc negative are 88.72% and 101.19 mlU/ml. Anti-HBs positive rate and GMC of 10 microg HepB-HPY are 94.20% and 162.17 mlU/ml, the Anti-HBs positive rate and GMC both have significant difference. CONCLUSIONS: The population whose HBsAg, Anti-HBs, Anti HBc negative vaccinated by HepB-Y, HepB-HPY can get better Anti-HBs response. The population younger than sixteen years old vaccinated by 10 microg HepB-HPY can get Anti-HBs positive rate and GMC higher than vaccinated by 5 microg HepB-Y. The Anti-HBs response of HepB-HPY is better than HepB-Y in the population > or =16 years old. PMID- 20575267 TI - [Analysis on effect of health promotion project for pupils in Wushan County]. AB - OBJECTIVE: To evaluate the effect of health promotion project ahout hepatitis for pupils, and provide strategies for health promotion. METHODS: Health promotion program was implemented through health education classes, along with many entertainments and lively activities. RESULTS: 213 teachers, pupils and parents from schools in the county were surveyed. The awareness of them were 100%, and the inoculating rates of hepatitis A vaccine and hepatitis B vaccine were hoth improved to 93%. CONCLUSIONS: Health promotion program plays an important role to promote the healthy knowledge of pupils. PMID- 20575268 TI - [Measles antibody level of productive women in Hongkou District of Shanghai Municipal]. AB - OBJECTIVE: To understand the level of measles antibody in productive women in Hongkou district in Shanghai, to provide evidence for immunization strategy. METHODS: Using quantitative enzyme-linked immunosorbent assay (ELISA) method to test the level of measles antibody IgG. RESULTS: Positive rate of measles antibody in productive women in Shanghai was 88.68%. The measles antibody's geometric mean concentration (GMC) was 814.73 IU/ml. Positive rate of measles antibody in floating productive women was 91.81%, and GMC was 1376.24 IU/ml. The positive rate of measles antibody decreased with age. CONCLUSION: The productive women should be vaccinated against measles vaccine before pregnancy so as to improve the antibody level. PMID- 20575269 TI - [Running and surveillance status of measles laboratory network in Gansu province in 2008]. AB - OBJECTIVE: To analysis the running status of measles laboratory network (MLN), and to provide the experience for measles surveillance. METHODS: The results of the confirmation data for measles specimen were analysed in 2008. RESULT: 4597 suspected measles cases were reported from MLN in Gansu in 2008, and 3762 sera samples were collected. The collection rate was 81.8%, 1879 of them were IgM positive for measles, and the positive rate was 49.9%. 1343 rubella sera specimen were detected, 611 of them were IgM positive for rubella, and the positive rate was 45.5%. According to the dentification from Chinese CDC, H1a genotype was only type of 3 measles strains found in Gansu by RT-PCR and nucleotide sequencing analysis. CONCLUSION: The laboratory network were running well in 2008. PMID- 20575270 TI - [Phylogenetic analysis based on hemagglutinin and neuraminidase genes between swine influenza virus and human influenza A/H3N2 virus strains isolated in Zhejiang province]. AB - OBJECTIVES: To investigate the phylogenetic relationship between swine influenza A/H3N2 virus and the representative strains of human influenza A/H3N2 virus isolated in two epidemics in recent years through comparing the sequences within HA and NA genes. METHODS: HA and NA gene of the human representative strains were sequenced, and then phylogenetic tree with the swine and human strains isolated in the corresponding period of time were constructed. RESULTS: The homologies on the HA1 domain between human representative strains (A/Zhejiang/10/98, A/Zhejiang/6/99 and A/Zhejiang/8/02)and the swine strains (A/SW/Ontario/130/97, A/SW/Hongkong/4361/99 and A/SW/Hongkong/74/02) were 99.1%, 99.4% and 99.4% respectively. Based on the NA gene, the homologies between human strains (A/Zhejiang/10/98, _A/Zhejiang/6/99 and A/Zhejiang/8/02)and the swine strains (A/SW/Ontario/130/97, A/SW/Hongkong/4361/99 and A/SW/Hongkong/74/02) were 98.2%, 99.3% and 99.3% respectively. The results showed that the two types of influenza viruses were highly homologue, and even some of their homologies were higher than that amongst the contemporary human influenza A/H3N2 strains. The same results shown in the phylogenetic tree. CONCLUSIONS: The human influenza A/H3N2 virus isolates in the two epidemic closely associated with some of the swine influenza virus strains, and their relationship should be further studied. PMID- 20575271 TI - [A prospective cohort study on community children vaccinated with Haemophilus influenzae type b]. AB - OBJECTIVE: To evaluate the epidemiological effect of Haemophilus influenzae type b conjugate vaccine (Hib). METHODS: Prospective Cohort Study was conducted to detect carrier rate of Hi in unvaccinated and vaccinated children by bacteria culture and Nest-PCR. Carrier rate of Hi and the incidence of lower respiratory tract infection in two groups children were analysed. RESULTS: The carrier rate of Hib in two groups children was very lower. The positive rate of NTHi in unvaccinated children was higher than vaccinated children significantly, which was mainly happened in the Children of 2-3 years old. The incidence of lower respiratory tract infection in unvaccinated children was higher than vaccinated children obviously. The protective effect of Hib vaccine against bronchitis was over 90%. The incidence of bronchitis of Hi culture positive was higher than that of Hi culture negative significantly. CONCLUSION: Children's bronchitis is related to the Hi carrier rate. To inoculate Hib vaccine can reduce the carrier rate of Hi and the incidence of bronchitis. PMID- 20575272 TI - [Surveillance of 494 viral encephalitis cases in Baoji Municipal during 2005 2007]. AB - OBJECTIVE: To understand the impact of surveillance system of viral encephalitis during 2005-2007 in Baoji city of Shaanxi province, to find epidemiological characteristic, control strategies and measurement to Japanese Encephalitis (JE). METHODS: Establishing the monitoring system of viral encephalitis, special monitoring of viral encephalitis cases was analyzed statistically by Epi data and Excel software. RESULTS: The seasonal trend of viral encephalitis was identical with that of JE, but the age of the incidence was different. Rate of missed diagnosis was 23.76%, squcalac cases was 5.5 times of the regular reported cases. The actual mortality was 7 times of the reported cases after 90 days and 180 days follow-up visit. CONCLUSIONS: Viral encephalitis monitoring and JE follow-up should be conducted in epidemic season so as to improve the accuracy of report and diagnosis of JE. PMID- 20575273 TI - [Epidemiological investigation and analysis on the death cases after vaccination in Shanghai, 2006-2008]. AB - OBJECTIVE: To evaluate the safety of vaccine by analyzing the death cases after vaccination. METHODS: To collect and analyze infomation of death cases related after vaccination in Shanghai during 2006-2008. RESULTS: In the 6 death cases reported after vaccination, 1 case was rare serious adverse events following immunization (AEFI), respiratory and circulatory failure caused by allergic disease. Other 5 cases were not related to vaccination. CONCLUSIONS: Coincidental event is common type in death after vaccination. Monitoring adverse events following immunization is the key measure to deal with the death cases following immunization. PMID- 20575274 TI - [Analysis on children timely vaccination coverage and influencing factors of 5 kinds of expanded program for immunization (EPI) vaccine in Dinghai District of Zhoushan Municipal]. AB - OBJECTIVE: To understand the timely coverage of 5 kinds of EPI vaccine in Dinghai District, including hepatitis B vaccine (HepB), bacillus calmette guerin vaccine (BCG), oral poliomyelitis attenuated live vaccine (OPV), diphtheria-pertussis tetanus combined vaccine (DPT), measles attenuated live vaccine (MV), and to analyze the influence factors so as to formulate measures to improve the coverage. METHODS: Analyzing the immunization data and related information of 4258 resident children and 394 floating population born during 2005-2007. RESULTS: Timely coverage rate of BCG, HepB, OPV, DPT, MV were 22.26%, 95.020, 90.82%, 91.40%, 95.40% respectively and 48.73%, 74.37%, 76.40%, 80.46%, 84.52%, for floating population. Except for the timely BCG coverage rate was low for resident and floating populations, the timely vaccination rates for other 4 kinds of NIP vaccines in the resident were significantly higher than those in the floating population. The logistic regression analysis showed that inappropriate timing of vaccination, long time waiting for inoculation, lacking of time for the families, long distance from the vaccination sites were four factors that affected the timely immunization of NIP vaccines. CONCLUSION: Implementing the strategy of midwife being responsible for BCG and HepB vaccination can improve the timely coverage of the first dose HepB and BCG: Shorten running inteval of vaccination and available service from the supplier, improve immunization awareness and initiative of the recipients (especially for the floating children's parent/guardian) will be useful to increase the timely NIP vaccine coverage rates. PMID- 20575275 TI - [Hepatitis B and hepatocellular carcinoma]. AB - Hepatitis B virus (HBV) is one of the most dangerous risk factors of hepatocellular carcinoma (HCC). How HBV infection leads to the occurrence and development of HCC is complicated. It is not only related with physical condition of HBV infection host, environment, HBV genotype, HBV viral load and gene mutation, but also related with age of HBV infection host, types of infection, and host chromosome integration site. PMID- 20575276 TI - [Development on timely first dose of hepatitis B vaccine for infants]. AB - The study on timely birth dose of hepatitis B vaccine for infants were reviewed in the article. The authors recommend that some relevant researches are necessary to be implemented in the areas which the coverage of HepB timely birth dose is at a low level in order to find out the influencing factors and intervention strategies to protect more children against hepatitis B virus infection as soon as possible. PMID- 20575277 TI - [Research progress on DNA tumor vaccine]. AB - DNA vaccine is one of the most attractive project in the research of vaccine now. DNA tumor vaccines mainly include tumor-associated-antigens-based completed, epitope, idiotope determinants DNA vaccine, fusion DNA vaccines, RNA self replicating vaccines, dendritic cell-based tumor vaccines etc. The recent developments are discussed in the article. PMID- 20575278 TI - Impact of improved air quality during the 1996 Summer Olympic Games in Atlanta on multiple cardiovascular and respiratory outcomes. AB - Substantial evidence supports an association between ambient air pollution, especially particulate matter (PM*) and ozone (O3), and acute cardiovascular and respiratory morbidity. There is increasing interest in accountability research to evaluate whether actions taken to reduce air pollution will result in reduced morbidity. This study capitalized on a unique opportunity to evaluate the impact of a local, short-term intervention effort to reduce traffic in Atlanta during the 1996 Summer Olympic Games (July 19-August 4). Air pollutant concentrations both inside and outside of Atlanta were examined during the Olympic period and surrounding periods. Emergency department (ED) visits were examined to evaluate changes in usage patterns. ED visits for respiratory and cardiovascular conditions were examined in relation to the Olympic period using Poisson time series analysis with adjustment for time trends and meteorologic conditions. O3 concentrations were approximately 30% lower during the Olympic Games compared with the four weeks before and after the Olympic Games (baseline periods); however, we observed similar reductions in O3 concentrations in several other cities in the Southeastern United States. We observed little or no evidence of reduced ED visits during the Olympic Games; the estimates were sensitive to choice of analytic model and to method of adjusting for temporal trends. The meteorologic conditions during the Olympic Games, along with the reductions in O3 observed in various cities not impacted by the Olympic Games, suggest that both meteorologic conditions-and reduced traffic may have played a role in the observed reduction in O3 concentration in Atlanta. Additionally, it is likely that this particular intervention strategy would not be sustainable as a pollution-reduction strategy. This study demonstrates some limitations of conducting retrospective accountability research. PMID- 20575279 TI - [Correct operation and reasonable choice of implant for intertrochanteric fracture of femoral]. PMID- 20575280 TI - [Complications of bipolar hemiarthroplasty for the treatment of unstable intertrochanteric fractures in the elderly]. AB - OBJECTIVE: To analyze the complications of bipolar hemiarthroplasty for the treatment of intertrochanteric fractures. METHODS: From Jan. 2004 to Dec. 2007, 62 patients over 80 years old with unstable interthochanteric fracture were treated with bipolar hemiarthroplasty, included 34 males and 28 females with an average age of 86.3 years ranging from 81 to 97 years. According to the Evans classification, there were 29 cases of Evans III, 26 of Evans IV and 7 of Evans V. The systemic and operation related complications were investigated. RESULTS: Among all the cases, 59 were followed up in outpatient department for 24 to 70 months (33 months on average). Systemic complications were found in 19 cases with no death during preoperative period and 5 deaths after leaving hospital. Operation related complications were found in 9 cases, included 3 cases of thigh pain, 1 iatrogenic fracture of proximal femur, 2 hip dislocations, 2 delayed union of fractures and 1 superficial infection. There were no aseptic loosening, peri-prosthetic infections,ectopic ossification or injuries of nerves and vessels. CONCLUSION: Bipolar hemiarthroplasty is indicated for patients over 80 years old with intertrochanteric fracture, thus the organic or systemic malfunctions should be corrected during perioperative period. Meanwhile, retaining of lesser trochanter and reconstruction of calcar femorale are important for improving periprosthetic biomechanics and reducing local complications. PMID- 20575281 TI - [Application of the anatomic plate and trapezoid plate in comminuted intertrochanteric fracture combined with trochanteric coronal position fracture: a controlled clinical trial]. AB - OBJECTIVE: To investigate the therapeutic effect and operative characteristic of the anatomic plate and trapezoid plate for treament of the comminuted intertrochanteric fracture combined with trochanteric coronal position fracture. METHODS: From Jan. 1998 to Mar. 2007, 57 patients suffered from comminuted intertrochanteric fracture combined with trochanteric coronal position fracture were randomly divided into two groups, 21 patients in trapezoid plate group were treated with the trapezoid compression plate, included 11 males and 10 females with an average age of 41.8 years; and 36 patients in anatomic plate group were treated with the anatomic plate, included 17 males and 19 females with an average age of 42.1 years. All of the 57 fractures were A3 type according to AO classification. The functions of hip joints were evaluated according to the Harris hip functional standard score. RESULTS: All 57 patients were followed-up for 5 months to 9 years and 3 months with an average of 4.8 years. The healing time of the fractures was from 8 to 20 weeks with an average of 12.8 weeks. The results of Harris scoring showed the pain scores of the anatomic plate group were higher than that of the trapezoid plate group (P < 0.05). The function scores of the anatomic plate group were higher than that of the trapezoid plate group (P < 0.01). There were no statistically significant different in the deformity and ranges of joint scores between two groups (P > 0.05). CONCLUSION: In unstable comminuted intertrochanteric fracture combined with trochanteric coronal position fracture, the lateral wall of trochanteric is often destroyed. The anatomic plate and the trapeziod compression plate can provide effective internal fixation, while many othere internal fixation methods were limited in this kind of fracture. As compared with the anatomic plate fixation, the trapezoid compression plate fixation of comminuted intertrochanteric fracture combined with trochanteric coronal position fracture have several advantages, such as fewer complications, faster union of fracture and earlier recovery of joint functions. PMID- 20575282 TI - [A report of diffuse giant cell tumor of the tendon sheath in total elbow]. PMID- 20575283 TI - [Minimally invasive treatment of intertrochanteric fractures with locking compression plate in the elderly]. AB - OBJECTIVE: To study the effect of minimally invasive treatment with the locking compression plate (LCP) in the treatment of intertrochanteric fractures in the elderly age. METHODS: Twenty-eight cases of intertrochanteric fracture were retrospective studied from August 2007 to January 2009, included 13 males and 15 females with an average age of 78.6 years ranging from 70 to 102 years. All the 28 patients were treated with minimally invasive operations with locking compression plates. The time from injury to operation was ranged from 3 to 8 days (with an average of 4.5 days). RESULTS: The operation time was from 40 to 90 minutes (with an average of 55 minutes). The average bleeding volume during the operation was 70 ml (from 50 to 150 ml). One patient died during hospital stay. Twenty-five patients were followed up from 6 months to 2 years with an average of 15 months after operation. The fracture healing time was from 10 to 12 weeks (10.4 weeks in average). According to an evaluation standard of HUANG Gong-yi, the results were excellent in 20 cases,good in 4 cases, poor in 1 case. CONCLUSION: Minimally invasive approaches with LCP could treat the elder intertrochanteric fractures with the advantages such as minimal invasive, stable fixation and less blood loss. PMID- 20575284 TI - [Analysis of the treatment failures for intertrochanteric fractures with dynamic hip screw (DHS)]. AB - OBJECTIVE: To analyze the reasons and related factors of failures in the treatment of intertrochanteric fracture with dynamic hip screw (DHS) and to increase the therapeutic level of intertrochanteric fracture. METHODS: All the 78 cases of intertrochanteric fractures were treated with dynamic hip screws from Dec. 1998 to Dec. 2007 included 42 males and 36 females with an average age of 62 years old ranging from 26 to 85 years. The disease course was from 1 to 49 hours (means 4 hours). According to Evans-Jensen classification of intertrochanteric fracture, 4 cases were type IA, 24 cases were type IB, 13 cases were type IIA, 22 cases were type IIB, 11 cases were type III, 4 cases were type IV. The fracture were fixed with dynamic hip screws following AO operative standard. To analyze the reasons and related factors of the 12 failed cases involving femur head and neck cut-off, tail pin exit, coxa vara, screw loosening, compress screw slip out of the tube, fracture displacement, respectively. RESULTS: All the cases were followed up for 13 months to 7 years with an average of 36 months, 12 cases were failed including 4 cases of femur head and neck cut-off, 1 case of coax vara, 2 cases of compress screw slip out of the plate tube, 2 cases of screws loosening, 2 cases of tail pin displacement 1 case of great trochanter fracture displacement. CONCLUSION: For intertrochanteric fracture, to interfix with dynamic hip screw is an effective method, the choice of indication, the type of fracture, the bone mineral density and the manipulative technique affect the results. PMID- 20575285 TI - [Experience of 21 mini-open for the treatment of fracture of tibial intercondylar]. PMID- 20575286 TI - [Radiographic imaging feature and differential diagnosis of early femoral head necrosis]. AB - OBJECTIVE: To study early femoral head necrosis radiographic imaging features to provide objective basis for the clinical differential diagnosis and therapeutic schedule's choice. METHODS: Ninty-one patients with femur head necrosis of ARCO stage I and II whom were diagnosed by clinic and MRI and treated from March 2007 to June 2008 were analyzed retrospectively. There were 32 males and 59 females with an average age of (34.83 +/- 9.57) years ranging from 21 to 60 years. The course of disease were from 2 to 12 months. There were 17 cases of unilateral and 74 of bilateral; 48 cases caused by steroid, 35 cases by alcohol and 8 cases for unknown reasons. The images of X-ray, CT and MRI of femoral head were analyzed to summarize the characteristic and to distinguish with the imaging of similar osteonecrosis. RESULTS: Ninety-one cases had linear low signal on T1WI in weight bearing area of femoral head and high signal of the "dual taxation" on T2WI. But the shapes had different characteristics. There were 36 cases (39.56%) of line type shapes, 28 cases (30.77%) of oval shapes, 14 cases (15.38%) of map-like shapes, 13 cases (14.29%) of wedge shapes. The X-rays of the disease similar to bone necrosis including primary hip osteoarthritis, developmental dysplasia of hip arthritis, femoral head epiphysitis (coxa plana), rheumatoid hip arthritis, hip arthritis of ankylosing spondylitis, transitional synovitis of hip joint, femoral head bone marrow edema etc, had the similar performance to femur head necrosis like cystic changes, joint space narrowing, femoral head deformation. MRI performance had their own characteristics. CONCLUSION: Mastering the image features of the early femoral head necrosis will help the early diagnosis and treatment of hip joint necrosis disease. PMID- 20575287 TI - [Rehabilitation treatment of spinal small joint disorder by manipulation]. PMID- 20575288 TI - [Clinical research of electroacupuncture combined with acupoint-injection of botulinum toxin A in treating the muscle spasticity by spinal cord injury]. AB - OBJECTIVE: To explore clinical safety and efficiency of electroacupuncture combined with acupoint-injection of botulinum toxin A for the treatment of muscle spasticity by spinal cord injury. METHODS: Thirty-eight patients with muscle spasticity by spinal cord injury were treated from December 2006 to December 2009 including 26 males and 12 females, with an average age of 45.4 years old ranging from 21 to 68 years. The patients were randomly divided into 3 groups according to admission time, 13 patients in group A were treated with electroacupuncture combined with acupoint-injection of botulinum toxin A, and 13 patients in group B were treated with acupoint-injection botulinum toxin A and 12 patients in group C were treated with electroacupuncture. After 6 months these patients were evaluated by improved muscle Ashworth scoring (MAS) and clinical spasticity index (SCI). RESULTS: Thirty-eight patients were followed-up at 6 months after the treatment. The result showed that the MAS scores of group A, B, C before treatment were (3.10 +/- 0.14), (3.20 +/- 0.17), (3.10 +/- 0.16) respectively and the CSI scores were (14.10 +/- 0.14), (14.30 +/- 0.11), (14.20 +/- 0.12) respectively; there were no statistical different among the three groups (P > 0.05). After 6 months of treatment, the MAS scores were (1.10 +/- 0.16), (2.10 +/ 0.13), (2.00 +/- 0.14) respectively and the CSI scores were (9.10 +/- 0.11), (12.10 +/- 0.14), (13.10 +/- 0.12) respectively. The MAS scores and CSI scores of group A were better than the other two groups (P < 0.05). CONCLUSION: The combination of Chinese hydropower needles and acupoints with BTX-A injection can achieve a comprehensive treatment and reduce pain and improve life quality quickly. The electroacupuncture combined with acupoint-inject botulinum toxin A is a noval safe and effective technique for the treatment of muscle spasticity by spinal cord injury. PMID- 20575289 TI - [Application of autotransfusion in the orthopaedic operations]. PMID- 20575290 TI - [Effect of ulinastatin on post-operative cognition disorders in elderly patients undergoing hip joint replacement]. AB - OBJECTIVE: To evaluate the effect of ulinastatin on post-operative Cognition disorders in elderly patients undergoing hip joint replacement. METHODS: Forty ASA I or II elderly patients undergoing selective hip joint replacement, aged > or = 65 years, were randomly divided into 2 groups (n = 40 each): control group and ulinastatin group. Ulinastatin group received iv infusion of ulinastatin (10,000 u/kg) after skin incision, (5,000 U/kg) after operation 1, 2, 3 d respectively, included 21 males and 19 females with an average age of (75.00 +/- 7.81) years old. Control group received the same volume of normal saline instead of ulinastatin, included 20 males and 20 females with an average age of (72.80 +/ 7.25) years old. Neuroeognitive testing was performed on the preoperative day and on the 3th postoperative day and post-operative cognition disorders was defined as 1 SD decline from baseline on neurocognitive assessment. Serum S100beta protein were measured before operation, at the end of surgery, 3, 24 h and 3 d after operation. RESULTS: The incidence rate of postoperative cognition disorders was 2.5% in ulinastatin group, there were lower than those of patients in the control group (25%) (P < 0.05); In control group, the scales for MMSE before and after operation were (25.2 +/- 2.1), (22.6 +/-2.5) scores and the level of serum S100beta protein at T0-4 were (0.041 +/- 0.012), (0.125 +/- 0.031), (0.178 +/- 0.036), (0.142 +/- 0.038), (0.048 +/- 0.015) microg/L. As well in ulinastatin group, above date were (25.9 +/- 2.4), (24.8 +/- 2.1), (0.040 +/- 0.013), (0.095 +/- 0.021), (0.116 +/- 0.017), (0.087 +/- 0.019) and (0.043 +/- 0.012) respectively. Compared with preoperative, MMSE evaluation scale was decreased on the 3th postoperative day and the S100beta was increased markedly at T1-3 in control group (P < 0.05); Compared with control group, MMSE evaluation scale was increased and the S100beta was decreased markedly at T1-3 in ulinastatin group (P < 0.05 ). CONCLUSION: Intravenous infusion of ulinastatin during operation can prevent the occurrence of POCD in elderly patients. PMID- 20575291 TI - [Clinical study of treatment of longitudinal fracture of patella with shape memory alloy patellar concentrator and lag]. PMID- 20575292 TI - [Preliminary evaluation and clinical application of unilateral decompression, interbody fusion and pedicle screw fixation under endoscopic system]. AB - OBJECTIVE: To explore the feasibility and efficiency of treatment of lumbar degenerative disease with unilateral decompression, interbody fusion and percutaneous pedicle screw fixation assisted by X-Tube systerm for the management of degenerative lumbar disease. METHODS: A total of 29 patients with degenerative lumbar,disease including 12 males and 17 females with an average age of 52.4 years ranging from 27 to 68 years, underwent minimally invasive posterior lumbar interbody fusion (PLIF) or TLIF assisted by the X-Tube system. The index diagnosis was discogenic low back pain in 11 cases, intervertebral space stenosis with unilateral herniated nucleus pulposus in 15 cases, recurrence after operation of lumbar intervertebral disc herniation in 3 cases. The diseased segment was in L4,5 in 18 cases, L5S1 in 11. RESULTS: The operative duration were 138 to 190 min (means 145 min); the blood loss was 230 to 560 ml (means 350 ml). Total 29 patients were followed-up from 5 to 19 months (means 9.8 months). The changes the clinical functional outcomes were evaluated according to the VAS pain score and the Oswestry Disability Index questionnaire. The VAS pain score decreased from (7.3 +/- 6.7) preoperatively to (2.3 +/- 0.8) at postoperative one month and (1.3 +/- 0.5) at final follow-up; The average ODI scores decreased from (44.8 +/- 7.1) preoperatively to (16.3 +/- 5.7) at postoperative one month and (2.6 +/- 4.5) at final follow-up. According to the Macnab criteria,the clinical effects were excellent in 19 cases, good in 7 cases and fair in 3 cases. Twenty five patients were followed-up more than 9 months, 23 cases of them had showed remarkale bony interbody fusion on the X-rays and CT. The outcomes of operation was satisfied. CONCLUSION: Minimally invasive PLIF assisted by X-Tube system minimize blood loss and tissue trauma, shorten the operative, recovery and bony union time, the short-term outcomes are excellent which make it a valuable alternative to conventional surgical procedures and suitable to segments from L2 to S1. The shortcomings are confined operating space and field of X-Tube system. PMID- 20575293 TI - [Supine posture reduction and mould combined with 8-shaped bandage fixation for the treatment of clavicular fracture]. PMID- 20575294 TI - [Study on the method of construct the three-dimensional finite element model of cervical vertebrae semidislocation]. AB - OBJECTIVE: Cervical vertebra semidislocation was one of major pathological aspects of cervical spondylosis, and it was also the target of manipulation to treat cervical spondylosis. The aim of this study was to combine the technology of three dimensional finite element analysis to investigate the method to construct the cervical vertebra semidislocation model. METHODS: A cervical spondylosis patient (male, 28 years old,176 cm tall, weight 69 kg) was randomly chosen, who was diagnosed cervical vertebra semidislocation by dynamic and static palpation and X-ray,and CT scanned from C1 to C7 by 0.75 mm slice thickness. Based on the CT data, the software was used to construct the three dimensional finite element model of cervical vertebra semidislocation (C4-C6). RESULTS: The model showed the three dimensional changes of vertebra semidislocation clearly. C5 had a three-dimensional abnormal position, which was downward translation for 0.9 mm and clockwise rotation for 4.5 degrees around X-axis. So C5 was diagnosed as hypokinesis-type semidislocation. CONCLUSION: The method to construct the three dimensional finite element model of cervical vertebra semidislocation is reliable, which provide a base study to analyse the mechanism of manipulation to treat vertebra semidislocation. PMID- 20575295 TI - [A study of a rat lumbar disc herniation model and the mechanism spontaneous of resorption]. AB - OBJECTIVE: To establish a new animal model of resorption of lumbar disc herniation. METHODS: Twenty 3-month-old Sprague Dawley (SD) male rats were randomly divided into experimental group and control group. The caudal discs of the experimental rats were surgically removed and were implanted in the epidural. The animals were killed at 30 days, and the implanted nucleus pulposus were took out for HE staining,flow cytometry and immunohistochemistry. In the control group, coils were implanted in the back muscles, and the animals were killed at 30 days after the operation for the above test. RESULTS: In the experimental group, immunohistochemical staining of TNF-alpha, VEGF were positive at 30 days. The Th cells and B cells in the experimental group were more than that in the control group with statistically significant differences. CONCLUSION: The model can well reveal the re-absorption process the of the ruptured disc, and provide a new re-absorption disc animal model for the further study. PMID- 20575296 TI - [Imaging diagnosis of synovial tuberculosis of sheath of wrist]. AB - OBJECTIVE: To investigate the imaging features of synovial tuberculosis of sheath of wrist. METHODS: Three patients of synovial tuberculosis of sheath of wrist underwent surgical operation from Oct. 2002 to Oct. 2009 included 2 males and 1 female, the age of 48, 67, 76 years respectivly. X-rays of 3 patients, CTs of 2 patients and MRI of 1 patient were retrospectively analyzed and the relevant literature were reviewed. RESULTS: There were 3 cases with the soft tissue mass in the palm side of wrist, the section was unclear. There were no osteoporosis and no changes of bone destruction. There was 1 case with the punctate calcification in the soft tissue. MRI showed the embedded cystic mass of flexor tendon and "8" shape in carpal tunnel pressure, and showed abnormal signal (T1 low-signal, T2 slightly higher signal), a small part of the internal point showed high signal. CT showed the synovial membrane were obvious thickening and enhanced, corpus liberum in tendon sheath were no obvious strengthening. CONCLUSION: Synovial tuberculosis of sheath of wrist has certain characteristics on radiographic image. The MRI has more clinical value than X-ray and CT. PMID- 20575297 TI - [The application of external fixation for the treatment of supracondylar femoral fracture after total knee replacement]. AB - OBJECTIVE: To explore the external fixation for treatment of supracondylar femoral fractures after total knee replacement. METHODS: From June 2005 to July 2007, 7 cases of supracondylar femoral fracture after total knee replacement were treated with external fixation included 4 males and 3 females with an average age of 71 years ranging from 55 to 85 years. The fracture healing were observed and the knee function were evaluated by the HSS scoring. RESULTS: All patients were followed-up for 6 to 23 months with an average of 12.5 months. The fracture healing time was from 6 to 12 weeks after operation (averaged 8.5 weeks). During the followed-up period, there were no infection and loosening, only one case occurred nail crossing delayed healing of skin. The HSS knee score was (60.6 +/- 16.0) before treatment and (77.6 +/- 11.6) after treatment according to HSS knee score criteria, the results were excellent in 2 cases, good in 4, and fair in 1. CONCLUSION: Application of external fixation for treatment of supracondylar femoral fracture after total knee replacement, especially in poor physical condition, high age patients is a more appropriate treatment. PMID- 20575298 TI - [X-ray analysis on 114 patients with moderate endemic skeletal fluorosis by treatment of Guo's Chinese herbal]. AB - OBJECTIVE: To observe the X-ray features of bone damage in patients with moderate endemic skeletal fluorosis and the changes of X-ray after treatment with herbal therapy. METHODS: From 2007.12 to 2009.8,114 patients with moderate endemic skeletal fluorosis were randomly divided into treatment group and control group by central randomization system. There were 60 patients in treatment group including 26 males and 34 females,aged from 39 to 60 years with an average of (51.68 +/- 4.98) years; There were 54 patients in control group included 30 males and 24 females, aged from 39 to 60 years with an average of (52.15 +/- 4.86) years. Both treatment and control groups were treated with basic treatment including calcium supplementation and preparation stage with herb decoction. Patients were orally given 600 mg Caltrate everyday for calcium suptrointestinal function and promoting the digestion and absorption of herb decoction for 3 days. Patients in treatment group were rally given Guo's Maqian decoction(200 ml,twice daily) for 8 weeks. Eight weeks later,Guo 's Maqian decoction was replaced y Guokangning capsule (0.44 g per cansule,2 capsules,three times daily) for 4 weeks. The treatment course lasted 12 weeks. The time for followed-up after treatment was 24 weeks. When the treatment finished, 7 experts on orthopaedics and radiology evaluated and statistically analyzed the X-ray features pre and post treatment,using expert evaluation scale (including the appearance and changes of osteosclerosis,osteoporosis softening,joint changes close to the bone and mixed changes) designed referring endemic skeletal fluorosis X-ray findings and sub-degree standard(WS192-2008). RESULTS: All X-ray features of endemic skeletal fluorosis appeared in the X-ray of the 114 patients with moderate endemic skeletal fluorosis. Osteosclerosis: 4 cases in forearm, 7 in calf,4 in pelvis,4 in lumbar vertebrae ;Osteoporosis and bone softening: 23 cases in forearm patients, 23 in calf, 5 in pelvis, 8 in lumbar vertebrae; Mixed changes: 6 cases in forearm, 9 in calf, 10 in pelvis, 1 in lumbar vertebrae patients; oint changes: 107 cases in forearm, 47 in calf, 28 in pelvis, 19 in lumbar vertebrae. There were X-ray no changes before and after the treatment in all of parts in control group. In treatment group, there were only 2 patients showed extraperiostealin and joint changes after the treatment, in which one showed better ossification of interosseous membrane of leg and another one showed disappearance of the lateral hyperplasia of the left pelvic acetabulum. There were no changes between before and after treatment in X-ray of all parts in the rest patiens of the treatment group. There was no significant difference between before and after treatment in both groups (P > 0.05). CONCLUSION: There is no obvious improvement in radiology of patients with skeletal fluorosis treated by Guo's therapy. PMID- 20575299 TI - [Effective analysis of continous perfusion with Dandshen and heparin for treatment of femoral head necrosis]. AB - OBJECTIVE: To investigate the effect of continous perfusion with Danshen and heparin for treatment of femoral head necrosis. METHODS: From April 2004 to June 2007,42 patients of femoral head necrosis were treated by contious perfusing with Dandshen and heparin, included 24 males and 18 females with an average age of 39.2 years ranging from 13 to 61 years. There were 18 patients on stage II, 13 patients on stage III, 11 patients on stage IV according to Ficat standard. The venous duct were inserted into femoral head then perfused Danshen and heparin into femoral head for 15 days. Every patient was carried out opacification before treatment and 1 month after operation. Every patient was evaluated according to Harris standard before treatment and 3, 6, 12 months after treatment. RESULTS: All patients were followed-up for 32 to 68 months (means 42.7 months). The average scores of 18 patients on stage II on 3, 6, 12 months after treatment were (88.43 +/- 3.41), (94.37 +/- 3.47), (92.84 +/-4.29), respectively, and the scores after treatment were higher than the score (78.23 +/- 3.47) after treatment. The average scores of 13 cases on stage III on 3, 6, 12 after treatment were (82.94 +/- 3.31), (88.60 +/- 2.31), (86.09 +/- 3.17) respectivly, and the scores after treatment were higher than the score (66.11 +/- 4.50) before treatment. The average scores of 11 cases on stage IV on 3, 6, 12 months after treatment were (61.31 +/- 4.06), (59.2 +/- 7.31), (54.62 +/- 8.20) respectivly,and the scores on 3, 6 months after treatment were higher than the score (50.16 +/- 2.35) before treatment,but there was no obvious difference between before treatment and 12 months after treatment. The rank of phlebography of 18 cases on stage II and 13 cases on stage IlI were improved obvi ously 1 month after treatment,but there was no obvious difference in 11 cases of stage IV. CONCLUSION: The method of contious perfusing with Danshen and heparin into femoral head has the advantage of little damage and good effect. It refers to patients in early stage (II and II ). PMID- 20575300 TI - [Operative treatment of old acetabular fractures]. AB - OBJECTIVE: To explore the operative methods and effects of treatment of old acetabular fractures. METHODS: From October 2001 to October 2007, 26 patients with old acetabular fractures were treated with operation including 21 males and 5 females with an average age of 34 years ranging from 18 to 65 years. On the basis of the three-dimensional computed tomography, all cases were diagnosed and classified according to Letourne-Judet classification, 9 cases were posterior wall fracture, 3 cases were lateropulsition fracture, 7 cases were lateropulsition and posterior wall fracture, 2 cases were posterior column and posterior wall fracture, 2 were T-shape fracture, 3 were dual column fracture. These patients were treated through the anterior,posterior, combined anterior posterior approaches. The time from injured to operation was 33 to 141 days (averaged 36.4 days). All the fractures were fixed with screws and AO reconstruction plates. RESULTS: All patients were followed up for 6 to 96 months, with an average time of 32.4 months. Evaluated according to Matta criteria, the results of scores was (5.04 +/- 1.04) on pain, (5.23 +/- 0.76) on range of motion, (4.92 +/- 1.16) on walking,and tatal (5.06 +/- 0.99) on average; The functional results of hip joints were excellent in 6 cases, good in 10 cases, fair in 6 cases, and poor in 4 cases. Sciatic nerve injury was found in 2 patients,lateral femoral cutaneus nerve injury in 3 patients, necrosis of femoral head in 1 patient,infection in 1 patient, and ectopic bone formation in 6 patients. CONCLUSION: Good clinical results can be obtained by careful selection of operative indications of old acetabular fractures in combination with proper operative approach and correct reduction and fixation. PMID- 20575301 TI - [Congenital insensitivity to pain with anhidrosis combined with habituation hip joint dislocation: a case report]. PMID- 20575302 TI - [Treatment of tarsometatarsal joint injury combined with metatarsal fracture by open reduction and internal fixation]. AB - OBJECTIVE: To evaluate the therapy and the key points of the tarsometatarsal joint injury combined with metatarsal fracture. METHODS: From Jan. 2006 to Jul. 2008,19 patients with tarsometatarsal joint injury combined with metatarsal fracture were treated with opened reduction and internal fixation of Kirschner wire or screws, included 13 males and 6 females with an average age of 38.1 years ranging from 21 to 56 years. The classification of tarsometatarsal joint injury showed that there were 2 cases of inner column injury, 5 cases of inner and medial column injury, 3 cases of lateral and medial column injury, 9 cases of tri column injury. There were 8 cases of shaft fracture, 7 of neck fracture, 19 of foundation fracture. RESULTS: All the incisions were first stage healed without skin necrosis. The healing time of fracture was 11.2 weeks on average. All the patients were followed-up for 6 to 17 months with an average of 12.8 months. According to the standard of AOFAS, the average score was (84.500 +/- 8.553), the results were excellent in 4 cases, good in 9 cases, fair in 3, and poor in 3. The regular daily life was recovered after 6.4 months, 3 patients suffer from mild osteoarthritis. CONCLUSION: No matter which fixed mode was used, the anatomical reduction was the most important to rebuild arches of the foot and recover medial longitudinal and lateral arch. Rebuilding arches of the foot guaranteed the integrity of the stress point scaffold and avoided the pain and limp. The anatomical reduction of tarsometatarsal joint and metatarsal was also important to rebuild the function of foot. PMID- 20575303 TI - [Operative treatment of nerve compression syndrome in ulnar nerve of elbow]. PMID- 20575304 TI - [Percutaneous locking plate combined with Sizhi-Xifang for treatment of the distal tibial fracture]. AB - OBJECTIVE: To observe the clinical effect of Sizhi-Xifang in the improvement of postoperative ankle function. METHODS: From Jan. 2006 to Mar. 2008,49 patients were divided randomly into treatment group and control group. The treatment group included 16 males and 8 females with an average age of (41.3 +/- 13.2) years, involving 13 cases of tye A, 9 of type B and 2 of type C based on AO classification. The control group included 15 males and 10 females with an average age of (38.2 +/- 10.9) years, involving 12 cases of type A, 10 of type B, 3 of type C. Minimal invasive percutaneous plate were used in each group. In treatment group 24 cases were treated with Sizhi-Xifang after the incisions were healed. RESULTS: There were no incision infections, flaps necrosis, bone and plate exposure after treatment in two groups. All patients were followed-up for 4 to 16 months with an average of 8.6 months. According to Johner-Wruhs evaluation standard, there were 7 cases in excellent, 12 good, 5 in fair in treatment group and in control group there were 5 cases in excellent, 7 in good, 10 in fair and 3 in poor. The comparison of effect between two groups had significant difference (P < 0.05). CONCLUSION: Sizhi-Xifang is helpful to improve the ankle postoperative function. PMID- 20575305 TI - [Clinical observation of the treatment of calcaneus fractures with Kirschner wire and absorbed screws fixation]. PMID- 20575306 TI - [Diagnosis and treatment for traumatic peroneal tendons dislocation]. PMID- 20575307 TI - [Application and progress of the finite element analysis model of cervical vertebrae]. AB - Finite element analysis (FEA) is broadly used in engineering, it was initially applied to simulate and solve a variety of engineering mechanics, thermal, electromagnetics, and other physical problems. The principle is a collective to be composed by an infinite number of particles, and an unlimited number of degrees of freedom from the continuum approximation. Brekelmas and Ryblcki firstly applied the finite element method to orthopedic biomechanics research in 1972. The first cervical vertebra finite element model was established in 1982 by Hosey. With the computer and software technology advances in the past 20 years, finite element method in cervical spine biomechanics studies is increased and widespread. PMID- 20575308 TI - Hepatitis E virus. PMID- 20575309 TI - Hepatitis E virus infection among pig handlers in Accra, Ghana. AB - OBJECTIVE: To determine the correlates of hepatitis E virus infection (HEV) in a sample of persons who work with pigs. DESIGN: Cross-sectional study. SETTING: Three pig farms in the Greater Accra Region of Ghana. SUBJECTS: Persons who work with pigs seen at the selected pig farms between the months of January and May 2008. RESULTS: One hundred and five persons who work with pigs voluntarily completed a risk-factor questionnaire and provided blood samples for unlinked anonymous testing for the presence of antibodies to HEV. The median age of participants was 36.5 +/- 15.0 years (range 12-65 years). Of the 105 subjects tested, HEV seroprevelance was 38.1%. On multivariate analysis, the independent determinants of HEV infection were being employed on the farm for less than six months (odds ratio (OR) 9.1; 95% confidence interval (95% CI) 1.0-81.4 and having piped water in the household and/or on the farm (OR 3.9; 95% CI 0.4-90.8). CONCLUSION: Consistent with similar studies worldwide, the results of our studies revealed a high prevalence of HEV infection in persons who work with pigs. Further studies need to be done to isolate, characterise the virus and define the clinical and epidemiological significance of HEV infection in this population. PMID- 20575310 TI - Characteristics of HIV-infected children seen in Western Kenya. AB - OBJECTIVES: To describe the characteristics and outcomes of children registered for care in a large HIV care programme in Western Kenya. DESIGN: A retrospective descriptive study. SETTING: USAID-AMPATH HIV clinics in health centres; district and sub-district hospitals; Moi Teaching and Referral Hospital in Western Kenya. SUBJECTS: HIV-infected children below age of 15 years seen in a network of 18 clinics in Western Kenya. INTERVENTIONS: Paediatric HIV diagnosis and care including treatment and prevention of opportunistic infections and provision of combination antiretroviral therapy (CART). MAIN OUTCOME MEASURES: Diagnosis, clinical stage and immune status at enrollment and follow-up; hospitalisation and death. Descriptive statistical analyses and chi square tests were performed. RESULTS: Four thousand and seventeen HIV-infected children seen between June 2002 and April 2008. Median age at enrollment was four years (0-14.2 years), 51% girls, 25% paternal orphans, 10% total orphans and 13% maternal orphans. At enrollment, 25% had weight-for-Age Z scores (WAZ) > or = -1 and 21% had WAZ scores < or = 3. Orphaned children had worse WAZ scores (p=0.0001). Twenty five per cent of children were classified as WHO clinical stage 3 and 4, 56% were WHO clinical stages 1 and 2 with 19% missing clinical staging at enrollment. Cough (25%), gastroenteritis (21%), fever (15%), pneumonia (10%) were the commonest presenting features. Twenty six per cent had been diagnosed with tuberculosis and only 25% started on cotrimoxazole preventive therapy (CPT). Median CD4% at enrollment was 16% (0-64%); latest recorded values were 22% (0-64). Sixty four per cent were on cART (cART+), median age at start was 5.4 (014.4 years). The median initial CD4% among cART+ was 13 (0-62) compared to 24 (0-64) for those not on ART (cART-). Median CD4% for cART+ improved to 22% (0-59); whereas cART- was 23% (0-64) at last appointment. During the period of follow-up, one fifth (19%) of children on cART were lost to follow-up compared to slightly over one third (37%) for those not on cART. Thirty four percent were hospitalised; 41% diagnosed with pneumonia. Six per cent of 4017 were confirmed dead. CONCLUSIONS: HIV infected children were enrolled in care early in childhood. Orphanhood was prevalent in these children as were gastroenteritis, fever, pneumonia and advanced immuno-suppression. Orphans were more likely to be severely malnourished. Only a quarter of children were put on cotrimoxazole preventive therapy. Children commenced on cART late but responded well to treatment. Loss to follow-up was less prevalent among those on cART. PMID- 20575311 TI - The contribution of very low birth weight deaths to infant mortality. AB - BACKGROUND: Infant mortality remains high in many developing countries in which the contribution of deaths among infants born very low birth weight (VLBW) may be considerable. This contribution has however not been quantified in most such countries. This paper explores a model that can be used in this respect. OBJECTIVE: To determine the contribution of very low birth weight infants towards the overall infants deaths in Kenya. DESIGN: Prospective cohort study. SETTING: Kenyatta National Hospital, Pumwani Maternity Hospital and Kilifi District Hospital. SUBJECTS: Very low birth weight infants followed up for a period of one year. RESULTS: The neonatal, post-neonatal and infant mortalities for the cohort were 442, 139 and 581/1000 respectively. These were thirteen, three and seven times higher than the national averages respectively. Of the national birth cohort of 1,300,000 during that year, it was estimated that between 15,600 (1.2%) and 24,700 (1.9%) were born VLBW. Given this VLBW infant burden and extrapolating the infant mortality observed in this study to the general population, between 9,064 (8.9%) and 14,351(14.2%) of the 101,400 (78/1000) infants who die during infancy in the country are born VLBW. CONCLUSION: The cohort reports very high infant mortality for VLBW infants when compared to the general population. Despite constituting less than 2% of the birth cohort, these infants contribute between 8.9% and 14.2% of all infant deaths. PMID- 20575312 TI - Intermittent presumptive treatment of malaria to prevent low birth weight in newborns in a cohort of pregnant women from a malaria endemic area. AB - OBJECTIVE: To determine and describe the patterns of low birth weight in newborns of a cohort of mothers given intermittent presumptive treatment (IPT) for malaria prevention in a malaria endemic area of Kenya. DESIGN: A longitudinal prospective cohort study. SETTING: Got Agulu Health Centre in Usigu Division, Bondo District, Nyanza Province. SUBJECTS: Pregnant women of all parities attending antenatal care services. Only women who gave informed consent for themselves and their newborns after birth were eligible to participate in the study. RESULTS: Parity was highly predictive of birth weight in the study subjects. Primigravidae and secondigravidae had a significantly lower mean birth weight (2952g) than women of higher gravidity (3214g) p-value <0.0001. Regardless of IPT administration, women who became positive for malaria infection at any point during pregnancy delivered 73.7% of the LBW infants. There was no significant difference in mean birth weights between primigravidae and multigravidae who had parasitaemia at baseline and at delivery (means 2906g and 3062g respectively, p=0.11). However, there was a significant difference between the parasitaemia negative primigravidae and multigravidae at baseline and at delivery (means 2952g and 3204g respectively, p=0.006). Infection with helminths did not have an effect on birth weight. Overall, low birth weight was observed in 9% of the newborns and was most commonly found in primigravidae and secondigravidae (14.8% and 13.1% respectively). CONCLUSION: Although many factors have been known to play a role in the causation of low birth weight (LBW <2500g), parity status and malaria infection in malaria endemic areas still play a major role regardless of IPT administration. PMID- 20575313 TI - Sporadic paediatric diarrhoeal illness in urban and rural sites in Nyanza Province, Kenya. AB - OBJECTIVE: Investigate differences in the infectious aetiology, health seeking behaviour, and provider practices with regard to diarrhoeal illness among children presenting to urban versus rural clinics in Western Kenya. DESIGN: Laboratory-based, passive surveillance. SETTING: The urban portion of the study was conducted at the paediatric outpatient clinic of Nyanza Provincial Hospital in Kisumu. The rural portion of the study was conducted at four outpatient clinics in the Asembo Bay community approximately 20 kilometers west of Kisumu. SUBJECTS: Children aged less than five years presenting to medical facilities for the treatment of diarrhoea from October 2001-October 2003 at the urban site and May 1997-April 2003 for the rural sites. RESULTS: Among the 1303 urban and 1247 rural specimens collected, 24% of specimens yielded a bacterial pathogen (24% urban, 25% rural). Campylobacter was the predominant bacterial pathogen (17% urban, 15% rural), followed by Shigella and nontyphoidal Salmonella (both 4% urban and 5% rural). In both communities, susceptibilities of these pathogens to the most commonly prescribed antibiotics was low (< or = 50%); 70% of all episodes of diarrhoea were prescribed antibiotic treatment. Urban health practitioners prescribed fewer antibiotics, chose drugs more likely to be effective, and were more likely to prescribe oral rehydration therapy for bloody diarrhoea. CONCLUSION: Most characteristics of diarrhoeal disease and their causes were similar in paediatric patients presenting to urban and rural clinics. Urban providers were more compliant with WHO recommendations. PMID- 20575314 TI - Factors related to attrition in a cohort study of HIV in Malawi. AB - BACKGROUND: Longitudinal studies face power reduction due to loss to follow up (LTFU). Bias may also arise because of differences between those who stay in the study and those who are LTFU. We studied factors associated with LTFU in a cohort of HIV seronegative and sera-positive mothers in urban Malawi. OBJECTIVE: To bridge the existing gaps by examining the factors associated with attrition. DESIGN: Longitudinal study. SETTING: Queen Elizabeth Central Hospital (QECH) and the Kamuzu Central Hospital in Blantyre, Malawi. SUBJECTS: One thousand three hundred and fifty three women who attended the prenatal clinic, between October 1989 and October 1990 were recruited as part of a study to determine rates and risk factors of sero-prevalence and sera-conversion of HIV-1 among this cohort. RESULTS: In this cohort study, 1353 women were enrolled at delivery and 1188 (88%) returned for the first follow-up visit at three months post-partum. Of those who returned, 177 (15%) were subsequently lost during the remaining months of follow-up. The main predictors of LTFU were younger maternal age, lower educational level of the father, HIV infection of the mother, lower birth weight of the index child and mother not being married. CONCLUSIONS: Researchers planning studies in developing countries should consider the impact of lower education and poorer infant health on study retention in developing countries. PMID- 20575315 TI - Trends and characteristics of home and other out-of-hospital births in the United States, 1990-2006. AB - OBJECTIVES: This report examines trends and characteristics of out-of-hospital and home births in the United States. METHODS: Descriptive tabulations of data are presented and interpreted. RESULTS: In 2006, there were 38,568 out-of hospital births in the United States, including 24,970 home births and 10,781 births occurring in a freestanding birthing center. After a gradual decline from 1990 to 2004, the percentage of out-of-hospital births increased by 3% from 0.87% in 2004 to 0.90% in 2005 and 2006. A similar pattern was found for home births. After a gradual decline from 1990 to 2004, the percentage of home births increased by 5% to 0.59% in 2005 and remained steady in 2006. Compared with the U.S. average, home birth rates were higher for non-Hispanic white women, married women, women aged 25 and over, and women with several previous children. Home births were less likely than hospital births to be preterm, low birthweight, or multiple deliveries. The percentage of home births was 74% higher in rural counties of less than 100,000 population than in counties with a population size of 100,000 or more. The percentage of home births also varied widely by state; in Vermont and Montana more than 2% of births in 2005-2006 were home births, compared with less than 0.2% in Louisiana and Nebraska. About 61% of home births were delivered by midwives. Among midwife-delivered home births, one-fourth (27%) were delivered by certified nurse midwives, and nearly three-fourths (73%) were delivered by other midwives. DISCUSSION: Women may choose home birth for a variety of reasons, including a desire for a low-intervention birth in a familiar environment surrounded by family and friends and cultural or religious concerns. Lack of transportation in rural areas and cost factors may also play a role. PMID- 20575316 TI - The challenge of presurgical orthodontics. PMID- 20575317 TI - Simultaneous reduction in vertical dimension and gummy smile using miniscrew anchorage. PMID- 20575318 TI - A simple method for aligning retroclined or ectopic teeth. PMID- 20575319 TI - The Smile Questionnaire. PMID- 20575320 TI - A simplified lingual technique. PMID- 20575321 TI - An improved version of the integrated Herbst appliance. PMID- 20575322 TI - Esthetic treatment planning for orthognathic surgery. PMID- 20575324 TI - Frugal cooking meatless meals. PMID- 20575323 TI - Coping with diabetes over time. PMID- 20575325 TI - Home cooking. Eat healthy, save money! PMID- 20575326 TI - Amylin. Insulin's super sidekick. PMID- 20575327 TI - Natural ways to lower your cholesterol. PMID- 20575328 TI - What your doctor is reading. PMID- 20575330 TI - Catch of the day. PMID- 20575329 TI - Chips and dips. PMID- 20575331 TI - Diabetes definitions. PMID- 20575332 TI - Acts of kindness and acts of novelty affect life satisfaction. AB - The present experiment was designed to establish the effects of acts of kindness and acts of novelty on life satisfaction. Participants aged 18-60 took part on a voluntary basis. They were randomly assigned to perform either acts of kindness, acts of novelty, or no acts on a daily basis for 10 days. Their life satisfaction was measured before and after the 10-day experiment. As expected, performing acts of kindness or acts of novelty resulted in an increase in life satisfaction. PMID- 20575333 TI - Perceived organizational support and turnover intention: the mediating effects of personal sacrifice and job fit. AB - This study examines the mediating role of job fit on the relationship between perceived supervisor support (PSS) and perceived organizational support (POS), and the mediating role of personal sacrifice on the relationship between POS and turnover intention. We use structural equation modeling (SEM) with a data set consisting of a sample of 346 individuals in a manufacturing firm to test our proposed model of PSS, POS, and turnover intention. Consistent with prior literature, our hypothesized model confirms that PSS is a predictor of POS and that POS is a predictor of turnover intention. By testing two additional competing and theoretically derived nested models, our findings indicate that job fit partially mediates the relationship between PSS and POS, and that personal sacrifice partially mediates the relationship between POS and turnover intention. Our study is among the first to examine job fit and personal sacrifice as mediators within the POS-turnover intention model. PMID- 20575334 TI - Perceiving racism in ambiguous situations: who relies on easy-to-use information? AB - In situations that are ambiguous with regard to the presence of discrimination, how do people arrive at their conclusions that discrimination has (or has not) taken place? This question was examined from a motivated social cognition perspective via the interaction of two factors: the prototype effect--the notion that ambiguously discriminatory behavior is more likely to be perceived as discriminatory when the executor is prototypical and the need for cognitive closure--the tendency to jump hastily to and seize on an answer. Results provided replicating evidence of the prototype effect among European American participants but not among African American participants. Specifically, European Americans were likely to perceive ambiguously racist behavior enacted by a prototypical executor (i.e., a White person) as more discriminatory than the same behavior exhibited by a non-prototypical executor (i.e., a Black person). African American participants, on the other hand, showed no reliance on this simple cognitive heuristic. Furthermore, results showed that European Americans with a higher need for cognitive closure were more likely to rely on the easy-to-use information offered by prototypes. These findings are discussed from a motivated social cognition perspective. PMID- 20575335 TI - The role of background behavior in televised debates: does displaying nonverbal agreement and/or disagreement benefit either debater? AB - This study examined the effects of background nonverbal behavior displayed with the purpose of undermining one's opponent in televised debates. Students watched one of four versions of a televised debate. In each, while the speaking debater appeared on the main screen, subscreens displayed her nonspeaking opponent's background nonverbal behavior. In one version, the non-speaking debater remained "stone faced" during her opponent's speech, while in the other three she nonverbally displayed occasional disagreement, nearly constant disagreement, or both agreement and disagreement. After viewing the debates, students rated the debaters' credibility, appropriateness, objectivity, and debate skills, in addition to judging who won the debate. Analysis indicated that background nonverbal behavior influenced audience perceptions of debaters' credibility, appropriateness, objectivity, debate skill, and the extent to which the debate was won. These results suggest that adding nonverbal agreement to expressions of nonverbal disagreement do not reduce the negative impacts of communicating disagreement nonverbally during an opponent's speech and may in fact further decrease the audiences' perception of a debater's credibility and overall performance. PMID- 20575336 TI - Physical attractiveness biases in ratings of employment suitability: tracking down the "beauty is beastly" effect. AB - The "what is beautiful is good" heuristic suggests that physically attractive persons benefit from their attractiveness in a large range of situations, including perceptions of employment suitability. Conversely, the "beauty is beastly" effect suggests that attractiveness can be detrimental to women in certain employment contexts, although these findings have been less consistent than those for the "what is beautiful is good" effect. The current research seeks to uncover situations in which beauty might be detrimental for female applicants. In two studies, we found that attractiveness can be detrimental for women applying for masculine sex-typed jobs for which physical appearance is perceived as unimportant. PMID- 20575337 TI - Step by step to integration. PMID- 20575338 TI - CMIOs should report to CEO. PMID- 20575340 TI - Staffing. Hospital hirings expected to rise. PMID- 20575339 TI - Physicians. Revising medical staff bylaws should be a three-way process, experts say. PMID- 20575341 TI - 'I'm always willing to help'. Interview by Laura Putre. PMID- 20575342 TI - Nursing. How are your nurses spending their time? PMID- 20575343 TI - Meaningful use. Hospitals advised to be thorough when deploying clinical decision support tools. PMID- 20575344 TI - When life gives you lemons. It is amazing what a 4-and-a-half-year-old can teach us about responding to adversity. PMID- 20575345 TI - Clinical integration. Fast forward to clinical integration. AB - Clinical integration has vaulted from idea to imperative, thanks in part to the new health reform law. This first installment of H&HN's series on the implications of the law looks at two health systems at very different points on the path to clinical integration. PMID- 20575346 TI - Umbdenstock: one big step, and many more to come. Interview by Bill Santamour. PMID- 20575347 TI - The ABCs of ACOs. What are they and how does your hospital fit in? PMID- 20575348 TI - Liability labs. Local experiments to resolve malpractice claims aims to be fairer to all sides. PMID- 20575349 TI - Integration: linking infection control and EMRs. PMID- 20575350 TI - Reforms hit home. Hospitals take charge of transforming health care. PMID- 20575351 TI - Denver Health. Transforming care across the continuum. PMID- 20575352 TI - Real reform begins nside the organization. PMID- 20575353 TI - Walking down the yellow brick road. PMID- 20575354 TI - Advocate Health Care. Embracing reform for the benefit of all. PMID- 20575355 TI - Trinity Health. Changing health care from the inside out. PMID- 20575356 TI - Weathering the storm. PMID- 20575357 TI - People process and technology: optimizing the IT benefits. PMID- 20575358 TI - Will you comply or optimize? Either way will require careful, coordinated planning and time is of the essence. PMID- 20575359 TI - Susceptibility of three stocks of pacific herring to viral hemorrhagic septicemia. AB - Laboratory challenges using specific-pathogen-free Pacific herring Clupea pallasii from three distinct populations indicated that stock origin had no effect on susceptibility to viral hemorrhagic septicemia (VHS). All of the populations were highly susceptible to the disease upon initial exposure, with significantly greater cumulative mortalities occurring in the exposed treatment groups (56.3-64.3%) than in the unexposed control groups (0.8-9.0%). Interstock differences in cumulative mortality were not significant. The virus loads in the tissues of fish experiencing mortality were 10-10,000 times higher during the acute phase of the epizootics (day 13 postexposure) than during the recovery phase (days 30-42). Survivors of the epizootics were refractory to subsequent VHS, with reexposure of VHS survivors resulting in significantly less cumulative mortality (1.2-4.0%) than among positive controls (38.1-64.4%); interstock differences in susceptibility did not occur after reexposure. These results indicate that data from experiments designed to understand the ecology of VHS virus in a given stock of Pacific herring are broadly applicable to stocks throughout the northeastern Pacific. PMID- 20575360 TI - Detection and prevalence of the nonsyncytial American grass carp reovirus Aquareovirus G by quantitative reverse transcriptase polymerase chain reaction. AB - The American grass carp reovirus (AGCRV) Aquareovirus G is not strongly associated with disease in fish, but it is often detected by cell culture during routine inspections of healthy fish. The cytopathic effect of AGCRV does not involve the typical syncytia associated with most aquareoviruses. Instead, the AGCRV produces a pattern of cell rounding that is very similar to that produced by rhabdoviruses, including those that are highly regulated. We have developed a quantitative polymerase chain reaction assay that can be used to identify AGCRV in cell cultures or directly on fish tissues. The assay detects as few as two copies of the plasmid template, has a coefficient of variation of 15% among assays performed on different days, and does not cross-react with any other aquareoviruses tested. Assays performed on tissues of cultured golden shiners Notemigonus crysoleucas and fathead minnow Pimephales promelas revealed a high prevalence of infection among healthy fish but no association with disease. PMID- 20575361 TI - Use of asiatic pennywort Centella asiatica aqueous extract as a bath treatment to control columnaris in Nile tilapia. AB - To develop antibiotic-free and chemical-free aquaculture, it is necessary to have natural substances to control diseases of aquatic animals. The aim of this study was to find an herb having therapeutic effect against columnaris, a fish disease caused by the bacterium Flavobacterium columnare. Of all tested herbs (including kalmegh Andrographis paniculata, candle bush Cassia alata, Asiatic pennywort Centella asiatica, mangosteen Garcinia mangostana, pomegranate Punica granatum, and guava Psidium guajava), the aqueous extract of Asiatic pennywort exhibited the strongest antimicrobial activity against F. columnare; the minimal inhibitory concentration was 31.25 lg/mL. It was also found to have a bactericidal effect on F. columnare. When experimental bath exposures of Nile tilapia Oreochromis niloticus to F. columnare were performed, the median lethal dose was determined to be 2.37 x 10(5) colony forming units/mL. For in vivo trials, six different concentrations (0, 20, 40, 60, 80, and 100 mg/L) of Asiatic pennywort aqueous extract were used as bath treatments to control experimentally induced columnaris in Nile tilapia. The decrease in fish mortality was dose dependent, and at a concentration of 100 mg/L no mortality or adverse effects were noted in the infected fish. This study suggests that Asiatic pennywort aqueous extract has the potential to control disease caused by F. columnare. PMID- 20575362 TI - Variation in susceptibility to Henneguya ictaluri infection by two species of catfish and their hybrid cross. AB - Proliferative gill disease (PGD) in channel catfish Ictalurus punctatus is caused by the myxozoan parasite Henneguya ictaluri. There is no effective treatment for PGD, and mortalities can exceed 50% in severe outbreaks. One approach to controlling losses would be to utilize a less susceptible ictalurid species in pond culture; alternatively, one could identify the traits that convey resistance and exploit them in a selective breeding program. Challenge studies have found less severe inflammatory responses in the gill tissue of blue catfish I. furcatus and fewer mortalities than in channel catfish. However, it remains unclear whether infection and subsequent plasmodial development progress the same way in the two species. To investigate this, we compared the dynamics of H. ictaluri infection in blue catfish, channel catfish, and channel catfish x blue catfish hybrids in continuous long-term (5-7-d) and short-term (24-h) pond challenges. After long-term challenge, 66.2% of the channel catfish and 63.6% of the hybrid catfish developed characteristic PGD lesions, compared with 3.7% of the blue catfish. Quantitative polymerase chain reaction analysis detected H. ictaluri in larger percentages of channel and hybrid catfish than blue catfish (98.7% and 95.7% versus 45.9%), with significantly greater parasite DNA equivalents in channel and hybrid catfish than blue catfish. Similar findings were obtained in the short-term exposures. Histologically, channel and hybrid catfish developed severe PGD accompanied by large numbers of developing plasmodia. While mild PGD was observed in some blue catfish, the progression of lesions lagged behind that in channel and hybrid catfish. Most importantly, developing plasmodia were not observed in blue catfish, and parasite DNA was not detected 14 d after removal from the source of infection. Our findings indicate that the resistance of blue catfish to H. ictaluri infection can be overcome by large numbers of infective actinospores but that infection appears to be eliminated before plasmodial development occurs. PMID- 20575363 TI - First record of a Polypodium sp. parasitizing eggs of shovelnose sturgeon from the Wabash River, Indiana. AB - This article reports the presence of an endocellular parasite, Polypodium sp., in the eggs of shovelnose sturgeon Scaphirhynchus platorynchus from the Wabash River, Indiana. The parasite was detected in 18% (2/11) of adult female sturgeon necropsied in April 2008. This constitutes the first record of this parasite in this host and in Indiana. The implications for the quality of the caviar remain unknown at this time. PMID- 20575364 TI - Antimicrobial susceptibility of Flavobacterium psychrophilum isolates from Ontario. AB - Flavobacterium psychrophilum is the etiological agent of bacterial coldwater disease (BCWD), an important disease in the Ontario fish farming industry and in finfish aquaculture in temperate waters worldwide. The development of antimicrobial resistance by F. psychrophilum is a concern because management of outbreaks of BCWD often requires the use of antibiotics. Seventy-two isolates of F. psychrophilum collected over a 16-year period from farmed salmonids with clinical signs of BCWD were tested for susceptibility to 10 antimicrobial agents using cation-adjusted Mueller-Hinton broth in custom Trek Sensititre susceptibility plates for aquaculture. The minimum inhibitory concentrations (MICs) for the isolates were determined by means of a broth microdilution antimicrobial susceptibility testing method established by the Clinical and Laboratory Standards Institute. Most of the F. psychrophilum isolates had decreased susceptibility to two of the four antibiotics licensed for use in Ontario (i.e., ormetoprim-sulfadimethoxine [> or =0.5/9.5 .tg/mL for 93% of isolates] and trimethoprim-sulfamethoxazole [> or = 0.25/4.8 microg/mL for 89% of isolates]). High MIC values (> or =2 microg/mL) were obtained for florfenicol and oxytetracycline in 53% and 61% of the isolates, respectively, and 83% of the isolates were relatively susceptible (< or =16 microg/mL) to erythromycin. The MIC values were also high for ampicillin, oxolinic acid, and gentamicin. PMID- 20575365 TI - Comparison of quantitative RT-PCR with cell culture to detect viral hemorrhagic septicemia virus (VHSV) IVb infections in the Great Lakes. AB - Viral hemorrhagic septicemia virus (VHSV) is an important pathogen of cultured and wild fish in marine and freshwater environments. A new genotype, VHSV IVb, was isolated from a fish collected from the Great Lakes in 2003. Since the first isolation, VHSV IVb has been confirmed in 28 species, signaling the early invasion and continued spread of this Office International des Epizooties reportable agent. For surveillance of this virus in both wild and experimental settings, we have developed a rapid and sensitive one-step quantitative real-time polymerase chain reaction (qRT-PCR) assay that amplifies a 100-base-pair conserved segment from both the genomic negative strand and the mRNA positive strand of the nucleoprotein (N) gene of VHSV IVb. This assay is linear over seven orders of magnitude, with an analytical capability of detecting a single copy of viral RNA and reproducibility at 100 copies. The assay is approximately linear with RNA input from 50 to 1000 ng per assay and works equally well with RNA prepared from a column-based or phenol-chloroform-based method. In wild-caught fish, 97% of the cases were found to be more than three orders of magnitude more sensitive using qRT-PCR than using cell culture. Of the 1,428 fish from the Great Lakes region tested in 2006 and 2007, 24% were positive by qRT-PCR whereas only 5% were positive by cell culture. All of the fish that were positive by cell culture were also positive by qRT-PCR. Importantly, qRT-PCR sensitivity is comparable to that of cell culture detection when comparing VHSV viral RNA levels with viral titer stocks, confirming that the high qRT-PCR signals obtained with diagnostic samples are due to the accumulation of N gene mRNA by transcriptional attenuation. The qRT-PCR assay is particularly valuable for rapid and high throughput prescreening of fish before confirmatory testing by cell culture or sequencing tissue-derived amplicons and especially in detecting infection in fish that do not show clinical signs of VHS. PMID- 20575366 TI - Firing an employee. Set the stage at time of hire. PMID- 20575367 TI - Testosterone deficiency. Common in midlife and beyond. PMID- 20575368 TI - Emotional overdrive. Understanding nonepileptic events. PMID- 20575369 TI - Pressure ulcer prevention. An update on strategies and terms. PMID- 20575370 TI - Status asthmaticus. Overview of treatment options. PMID- 20575371 TI - Hidradenitis suppurativa. Chipping away at causes and cures. PMID- 20575372 TI - Acute conjunctivitis in convenient care. PMID- 20575373 TI - Are men from Mars? When it comes to healthcare, maybe. PMID- 20575374 TI - Care of the bariatric patient. Health concerns after surgery. PMID- 20575375 TI - [Correlation analysis between single nucleotide polymorphism of beta-amyrin synthase and content of glycyrrhizic acid in Glycyrrhiza uralensis]. AB - OBJECTIVE: To analyze the correlation between content of glycyrrhizic acid and the single nucleotide polymorphism of beta-amyrin synthase (bAS) in Glycyrrhiza uralensis. METHOD: glycyrrhizic acid content in 80 samples of the cultivated G. uralensis were determined by HPLC; According to the very significant level (P < 0.000 1), 80 samples in accordance with glycyrrhizic acid will be grouped by SAS 9.0; Using RT-PCR strategy to amplification the Open Reading Frame of beta-amyrin synthase with the template of total RNA extracted from roots of G. uralensis and then using DNAman to analyze the relationship between glycyrrhizic acid content and the single nucleotide polymorphism of beta-amyrin synthase (bAS). RESULT: There exited two mutation sites 94 bp and 254 bp, G/A conversion occurred at 94 bp site, which belonged to a missense mutation. G/A conversion led to the corresponding amino acid conversion (Gly --> Asp); C/T conversion occurred at 254 bp site, which belonged to a synonymous mutation. According to sequence variation, the samples were divided into four genotypes: G-T genotype, A-T genotype, G/A-C genotype and G-T genotype. CONCLUSION: A-T genotype, G/A-C genotype and G-T genotype are correlated with the high content of glycyrrhizic acid. PMID- 20575376 TI - [Distribution and morphological variation of germplasm resource of Sophora alopecuroides]. AB - OBJECTIVE: To analyze the genetic difference of biological characters on germplasm resources of Sophora alopecuroides. METHOD: Twenty-three populations of S. alopecuroides from Ningxia, Gansu, Qinghai, Xinjiang and Inner Mongolian were used to analyze the seed size, 1 000-grain weight, and germination characteristics and so on. RESULT: It showed that there were significant differences in seed size, 1 000-grain weight and the vitality of seeds. The biggest seed of S. alopecuroides was 4.7 mm x 3.5 mm, and the smallest was 3.8 mm x 2.9 mm, and the 1 000-grain weight was 15-26 g. Results of seeds vitality in 8 populations indicated that the highest vitality of seeds were No. 103 and No. 122. The germination index was 36.51 and 36.24 respectively, and the vitality index was 1 323.49 and 1 274.56. The coefficient of variation in seed traits exceeded 10% except the seed size. CONCLUSION: There are some differences and different heredity background in various S. alopecuroides germplasm resources. PMID- 20575377 TI - [Influence of harvest times and processing methods on contents of total flavonoids and total saponins in roots of Ophiopogon japonicus]. AB - OBJECTIVE: To study the patterns of dynamic accumulation of total flavonoids and total saponins in the roots of Ophiopogon japonicus collected from different harvest times, and compare the contents of total flavonoids and total saponins in roots of O. japonicus which were processed with different methods. METHOD: The total flavonoids and total saponins contents in O. japonicus were determined by ultraviolet spectrophotometry. RESULT AND CONCLUSION: From December to January, the total contents of flavonoids and saponins in the roots of O. japonicus gradually decreased, and gradually increased from February to March, and kept stable in April. The contents of total flavonoids and total saponins in the O. japonicus were influenced by different processing methods. PMID- 20575378 TI - [Correlation of main physiological characteristics and active components in cultivars of medicinal Chrysanthemum morifolium]. AB - OBJECTIVE: To investigate the dynamic changes of main physiological indexes, active constituent of Chrysanthemum morifolium and their correlation during the whole growing period and provided a reference basis for the field production. METHOD: Take Ch. morifolium cv. Xiaobaiju, Ch. morifolium cv. Hongxinju and Ch. morifolium cv. Changbanju were taken as the research objects, the main physiological and biochemical indexes were determined, the correlation among them was analyzed. RESULT: The trend of each main physiological index and active component were different during the whole growing period. Agronomic characters, physiological and biochemical indexes and economic characters had correlation in different degree. CONCLUSION: Varieties with higher plant height, more branch and cephaloid numbers may be used for breeding for high yield, and varieties with higher chlorophyll content and POD activity, lower GSH content and SOD activity may be used for breeding for high content of the active components. PMID- 20575379 TI - [Research on callus induction and plantlet regeneration of Prunella vulgaris]. AB - OBJECTIVE: To study the conditions of callus induction and plantlet regeneration of Prunella vulgaris. METHOD: By using the orthogonal experiment design, different explants, sucrose, plant growth substances and their ratio for callus induction and differentiation were optimized. RESULT AND CONCLUSION: The inductivity of leaves was the highest, followed by stems, but callus of the leafstalks could not be induced. The main factor of affecting the formation of callus was 6-BA. The optimal medium for callus induction was MS + 6-BA 3.0 mg x L(-1) + NAA 0.1 mg x L(-1) + 2,4-D 0.5 mg x L(-1) + sucrose 3%. The optimal medium for callus differentiation was 1/2 MS + 6-BA 3.25 mg x L(-1) + NAA 1.25 mg x L(-1) + sucrose 2%. The optimal medium for rooting was MS + IBA 1.0 mg x L(-1) + sucrose 3%. PMID- 20575380 TI - [Determination of tractylodinol in different populations of Atractylodes lancea]. AB - OBJECTIVE: To establish an RP-HPLC method for determination of atractylodinol in Ateractylodes lancea and compare the contents of atractylodinol in the herbs of different origins. METHOD: The samples were separated on an Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) column with the mobile phase of acetonitrile-water (49:51). Flow rate was 1.0 mL x min(-1). The detection wave length was set at 337 nm. Column temperature was 30 degrees C. RESULT: The linear range of atractylodinol was 9.12 x 10(-2) -9.12 mg x L(-1) (r = 0.999 9), the average recovery was 97.15%, RSD was 1.5% (n = 5). The contents of atractylodinol were in the range of 0.268-1.213 mg x g(-1) in the samples from different orgins. The contents of atractylodinol in samples growing in Dabieshan mountain were higher than those in Jiangsu province (P < 0.001). CONCLUSION: The established method for determination of atractylodinol is accurate and reliable, which can be used to evaluate the quality of A. lancea, the contents of atractylodinol in the sample was related with its morphological characteristic and geographic orgin. PMID- 20575381 TI - [Pathogen identification of Pinellia ternata tuber disease and selection of fungicide]. AB - The rotten tuber of Pinellia ternata was found as an important disease during the growing season in Tianshui production area. The isolated pathogens were tested following Koch's postulates and identified as Fusarium oxysporum. The suitable growth conditions for the F. oxysporum were 15-30 degrees C, pH 6-8, the optimal condition was 21.9 degrees C and pH 7.2. Some fungicides were demonstrated to be effective to inhibit the pathogen growth. 70% thiophanate-methyl and 58% metalaxyl MZ were most effective to inhibit the pathogen. The EC50 were 0.002 7, 0.066 2 g x L(-1), respectively. PMID- 20575382 TI - [Preparation and study in vitro of 20 (S)-protopanaxadiol pharmacosomes]. AB - To prepare and evaluate in vitro the 20 (S) -Protopanaxadiol (Ppd) pharmacosome. The Ppd pharmacosome was successfully prepared by thin film-dispersion and its stability in vitro was studied. The particle size of pharmacosome was evaluated by dynamic scattering (DLS) and the encapsulation efficiency was determined by using centrifugal ultra-filtration. The encapsulation efficiency of Ppd pharmacosome was (80.84 +/- 0.53)% with the diameter of 100. 1 nm; While the encapsulation efficiency of Ppd pharmacosome that added Brij 78 added was (72.76 +/- 0.63)% with the diameter of 117. 3 nm. In addition, the effect of some factors on the encapsulation efficiency and the particles size, such as temperature, alcohol, pH and artificial gastrointestinal fluids, were investigated respectively. The selected formulation and technology are simple and practical to prepare Ppd pharmacosome and preparation properties are more stable. PMID- 20575383 TI - [Study on moisture sorption process model and application traditional Chinese medicine extract powder]. AB - OBJECTIVE: Study on the moisture sorption process characteristics of traditional Chinese medicine extract powder, to establish a mathematical model, provide a new method for in-depth study for moisture sorption behavior of traditional Chinese medicine extract powder and a reference for determine the production cycle, and predict product stability. METHOD: Analyzed moisture absorption process of traditional Chinese medicine extract powder by utilized the law of conservation of mass and Fick's first law to establish the double exponential absorption model, fitted the moisture absorption data and compared with other commonly used five kinds of model to estimate the double-exponential absorption model. RESULT: The statistical analysis showed that the coefficient of determination (R2) of double exponential model, Weibull distribution model and first order kinetics model were large, but the residues sum of squares (RSS) and AIC values were small. Synthesized the practical application meaning, we consided that the double exponential model was more suitable for simulating the process of Chinese medicine extract powder moisture absorption. CONCLUSION: The double exponential is suitable for characterization the process of traditional Chinese medicine extract moisture absorption. PMID- 20575384 TI - [Variation and regularity of volatile oil constituents in fruits of national medicine Cinnamomum migao]. AB - OBJECTIVE: To compare the constituents of the volatile oil in Cinnamomum migao from different regions of southwest in China in order to evaluate the quality of C. migao. METHOD: GC-MS was employed to analyze the constituents of the volatile oil in C. migao. RESULT: The volatile oil compositions of C. migao collected from 27 of cultivation regions were obviously different. Based on the chemical differences of the volatile oil compositions, C. migao was divided into four chemotype, they were eucalyptol, eucalyptol -cyclohexene, eucalyptol -alpha terpineol, and eucalyptol -sabinene. The eucalyptol-type was cultivated in Luodian, guizhou province and Funing regions, Yunan province. The eucalyptol cyclohexene-type was cultivated in Zhengfeng and Wangmo regions, Guizhou province. The type of eucalyptol, eucalyptol -sabinene and eucalyptol -alpha terpineol were cultivated in Ceheng and Libo regions, Guizhou province. CONCLUSION: Combined with the geographical distribution, It is indicated that the volatile oil compositions in fruit of C. migao may have some relations to the specie itself characteristics and different elevations environment. PMID- 20575385 TI - [Study on preparation of icaritin by enzymolysis of icariin with snail hydrolase]. AB - OBJECTIVE: To optimize the conditions for enzymolysis of Icariin by snail hydrolase. METHOD: Take conversion rate as index, the effects of pH, temperature, reaction time, dosage of enzyme, concentration of Icariin and metal ion on hydrolysis were studied by single-factor designs and a L9 (3(4)) orthogonal design. The product was characterized through MS, 1H-NMR and 13C-NMR methods. RESULT: The optimum enzymolysis conversion rate was achieved at 37 degrees C, pH 6.0 acetic acid-sodium acetate buffer solution and 48 h. The Ca2+, Mg2+ and Zn2+ had activation on helicase slightly but the Fe2+ inhibited enzymolysis significantly. The production was presumed as icaritin on the basis of spectral evidences. CONCLUSION: Snail hydrolase can be used for preparing of icaritin. The condition is mildness and suitable for industrialization. PMID- 20575386 TI - [Chemical constituents from fruits of Ligustrum lucidum]. AB - OBJECTIVE: To study the chemical constituents from the fruits of Ligustrum lucidum. METHOD: The chemical constituents from the ethanol extract of L. lucidum were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatographic methods. Their structures were identified on the basis of spectroscopic data and physico-chemical properties. RESULT: Twenty compounds were isolated and identified as oleanolic acid (1), crategolic acid (2), acetyl oleanolic acid (3), lupeol (4), betulin (5), dammarenediol-II (6), 3beta-acetyl 20, 25-epoxydammarane-24alpha-ol (7), 25-epoxydammarane-3beta, 24alpha-diol (8), dammar-24-ene-3beta-acetyl-20S-ol) (9), 20S, 24R-dammarane-25-ene-24-hydroperoxy 3beta, 20-diol (10), fouquierol (11), oliganthas A (12), dammarenediol II 3-O palmitate (13), ocotillol II 3-O-palmitate (14), (E) -25-hydroperoxydammar-23-ene 3beta,20-diol (15), verbascoside (16), cimidahurinine (17), 2-(3,4 dihydroxyphenyl)-ethyl-O-beta-D-glucopyranoside (18), osmanthuside H (19), 2-(3,4 dihydroxyphenyl) ethanol (20). CONCLUSION: Compounds 4, 16,17, 19 were isolated from this plant for the first time, andcompounds 12-15 were isolated from this genus for the first time. PMID- 20575387 TI - [Chemical constituents from Myricaria alopecuroides]. AB - OBJECTIVE: To investigate the chemical constituents in the leaves and branches of Myricaria alopecuroides. METHOD: Solvent extraction method was employed to extract and partition. The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20, highly porous resin HP-20. The structures of the compounds were elucidated on the basis of physiochemical properties and spectral analysis. RESULT: Eleven compounds were isolated from this plant and identified as ellagic acid 3,3',4-trimethylether (1), ellagic acid 3,3'-dimethylether (2), isorhamnetin (3), kaempferol (4), 3, 5-dihydroxy-4 methoxybenzoic acid (5), daucosterol (6), 6,7,10-trihydroxy-8-octadecenoic acid (7), quercetin (8), gallic acid (9), palmitic acid (10), hexadecanoic acid, 2,3 dihydroxypropyl ester (11). CONCLUSION: Except 8 and 9, all compounds were isolated from M. alopecuroides for the first time. Compound 1, 2, 5, 7, 10, 11 were obtained from the genus Myricaria for the frist time. PMID- 20575388 TI - [Chemical constituents from Lagotis brevituba]. AB - OBJECTIVE: To study on the chemical consitituents of Lagotis brevituba. METHOD: The chemical consitituents were isolated by silica gel column chromatography, polyamide column chromatography and semi-preparative HPLC, and their structures were identified by spectroscopic methods. RESULT: Eight compounds were isolated and they were identified as beta-sitosterol (1), succinic acid (2), luteolin-7-O beta-D-glucoside (3), uracil (4), apigenin (5), chrysoeriol (6), chrysoeriol-7-O beta-D-glucoside (7), and apigenin-7-O-beta-D-glucoside (8). CONCLUSION: Compound 4-8 were isolated from L. brevituba for the first time, and among them, compound 7 and 8 were isolated from genus Lagotis for the first time. PMID- 20575389 TI - [Microbiological transformation of paeoniflorin and albiflorin]. AB - OBJECTIVE: To investigate the microbiological transformation of paeoniflorin and albiflorin. METHOD: The bacteria strains able to transform paeoniflorin and albiflorin were screened from 18 strains of microorganisms. The products were isolated by chromatography method and their structures were elucidated by spectral technology. RESULT: It was found that Cunninghamella blakesleana (AS 3.970) and Syncephalastrum racemosum (AS 3.264) could convert paeoniflorin and albiflorin efficiently, respectively. C. blakesleana could convert paeoniflorin to produce albiflorin, while S. racemosum could convert albiflorin to produce paeoniflorin. CONCLUSION: Paeoniflorin and albiflorin could be converted each other in definited condition. PMID- 20575390 TI - [Comparison of volatile oils of cultivated Houttaynia cordata populations with wild]. AB - OBJECTIVE: To provide scientific proofs for the exploitation, utilization, and normalized cultivation of Houttuynia cordata. METHOD: The underground parts of 17 wild H. cordata populations from different valleys and altitudes of mountain. Emei were transplanted to the same growth conditions. After one year's cultivation, volatile oil was obtained by steam distillation from the aerial part of the materials. The chemical constituents were separated and identified by GC MS, and the relative content of each constituent was determined by area normalization. RESULT: Totally, 31 chemical components were identified, 19 components could be detected in all materials. The t-test results indicated that the contents of alpha-pinene and D-limonene were extremely significantly higher than that in the wild populations, and the contents of camphene and 2-undecanone were also significantly higher than that in the wild populations. And the reverse was found in the content of trans-beta-ocimene. All these 31 components could be divided into 9 chemical compositions, and 7 chemical compositions could be detected in the wild and cultivated. RSD values of 5 chemical compositions in wild populations were higher than that in the cultivated, except for the contents of diterpenyl alcohols and diterpenyl aldehydes. These five chemical compositions accounted for 84.05% and 90.12% of the whole volatile oils in the wild and cultivated conditions, respectively. CONCLUSION: The components and contents of the volatile oils between wild and cultivated were different. The volatile oils polymorphism decrease distinctively as all the wild populations of H. cordata were transplanted to the uniform environmental conditions. PMID- 20575391 TI - [Determination of tomatine in Solanum cathayanum by RP-HPLC]. AB - OBJECTIVE: To develop an HPLC method for determination of tomatine in the dried Solanum cathayanum of China Hubei Enshi. METHOD: The analysis was performed on a YMC-Pack ODS-AA column (4. 6 mm x 150 mm, 5 microm) eluted with acetonitrile and water in gradient mode. The concentration of acetonitrile in the mobile phase changes from 20% to 100% within 60 minutes. The detection wavelength was set 203 nm. The flow rate was 1.0 mL x min(-1) and column temperature was set at 30 degrees C. RESULT: The linear relationship of tomatine was determined within the range from 0.1-0.6 g x L(-1) (r = 0.999 7). The average recovery as 98.93% with RSD 1.2%. CONCLUSION: A convenient and reliable method was developed to determine the content of tomatine in the dried S. cathayanum. PMID- 20575392 TI - [HPLC determination of chikusetsusaponin IVa in Rhizoma Panacis Majoris from different producing areas]. AB - To determinate the chikusetsusaponin IVa in Rhizoma Panacis Majoris from different producing areas. The HPLC separation was performed on a Inertsil ODS-sp column (4.6 mm x 150 mm, 5 microm). A mixture of acetonitrile and 0.2% phosphoric acid solution (35:65) as the mobile phase the column. Temperature was set in 30 degrees C. The flow rate was 1.0 mL x min(-1), and the wave length of the detector is 203 nm. The content of the chikusetsusaponin IVa in Rhizoma Panacis Majoris from Meixian, Shaanxi is the highest and the lowest is from Enshi, Hubei. There have most differerence among the content of the chikusetsusaponin IVa in Rhizoma Panacis Majoris from different producing areas. PMID- 20575393 TI - [Effects of triptolide on cell proliferation and regulation of Ras-MAPKs pathway in synoviocytes induced by tumor necrosis factor]. AB - OBJECTIVE: To investigate the effects of triptolide on proliferation and regulation of ras-MAPKs pathway in human fibroblast-like synoviocytes of rheumatoid arthritis (RA-HFLS) treated with tumor necrosis factor (TNF-alpha). METHOD: RA-HFLS were cultured with TNF-alpha in the presence or absence of variable doses of triptolide (0.28, 2.8, 28, 140 nmol x L(-1)) in vitro. Cell proliferation was evaluated by MTS assay. The phosphorylation status of Ras-MAPKs associated proteins (Ras, p-P38, p-ERK and p-JNK) were detected by Western blot analysis. RESULT: Triptolide could obviously decrease the RA-HFLS viability in a dose-dependent manner and the inhibition ratio was 0.28%, 5.05%, 30.83% and 43.77% respectively. In addition, triptolide could also suppressed the expression of Ras, p-P38, p-ERK and p-JNK. CONCLUSION: Triptolide has an notable inhibiting effect on proliferation of RA-HFLS and the molecule mechanism is due in part to the direct suppression of abnormal activation of Ras-MAPKs pathway. PMID- 20575394 TI - [Antidysmenorrheic effects of Radix angelica and Rhizoma Chuanxiong with different proportions and preparation methods on dysmenorrhea model mice]. AB - OBJECTIVE: To study the effect of Radix Angelica and Rhizoma Chuanxiong with different proportions (1 : 0, 2 : 1, 1.5 : 1, 1 : 1, 1 : 1.5, 1 : 2, 0 : 1), different extraction in order (by water, by ethanol, firstly by alcohol then by water) on dysmenorrhea model mice in order to observe their compatibility rules and material foundation. METHOD: The mice model of primary dysmenorrhea was used to study the effect of Radix Angelica and Rhizoma Chuanxiong with different proportions and preparation methods on writhing response and the levels of nitric oxide and calcium ion in mice uterine tissue. RESULT: Danggui-Chuanxiong (1. 5 : 1) and solution extracted firstly by alcohol then by water showed the strongest effect on primary dysmenorrhea by reducing the writhing times, increasing nitric oxide (NO) concentration and reducing calcium ion (Ca2+) concentration in uterine tissue. CONCLUSION: Radix Angelica and Rhizoma Chuanxiong with different proportions and preparation methods showed different antidysmenorrheic trend on dysmenorrhea model mice, which was related with the containing constituents. PMID- 20575395 TI - [Effect of Jimaitong tablet combined with nifedipine on blood-pressure and mechanisms investigation in spontaneously hypertensive rats]. AB - OBJECTIVE: To study the effect and its mechanism of antihypertensive of drug combination of Jimaitong tablt and nifedipine on spontaneously hypertensive rats. METHOD: The spontaneously hypertensive rats (SHR) were treated by intragastric administration (ig) with Jimaitong (450 mg x kg(-1)), Jimaitong (300 mg x kg(-1)) combined with the nifedipine (0.5 mg x kg(-1)), nifedipine (5 mg x kg(-1)) for 8 weeks. Blood pressure and heart rate was measured. The level of oxidation indicators, lipid indicators, as well as hormones related to blood pressure was detected. RESULTS: Compared with that in the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure of SHR decreased significantly in all the three administration groups (P < 0.01). Heart rates of nifedipine group was faster than other groups (P < 0.05). In combination group, contents of URE, MDA, ET and Ang II were decreased significantly (P < 0.05, P < 0.05, P < 0.05, P < 0.01), the contents of NO and CAMP, SOD and NOS were significantly enhanced (P < 0.05). CONCLUSION: Combination use of Jimaitong and nifedipine has synergistic effects on anti-hypertension in spontaneously hypertensive rats. It indicates the potential applications of combination of traditional Chinese medicine and western medicine for the hypertension treatment. PMID- 20575396 TI - [Comparative study on pharmacokinetics of tetramethylpyrazine, ferulic acid and their compatibility]. AB - OBJECTIVE: To study the pharmacokinetics of tetramethylpyrazine (TMP), ferulic acid and their compatibility. METHOD: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: TMP 20 mg x kg(-1), ferulic acid 20 mg x kg(-1) and TMP 20 mg x kg(-1) + ferulic acid 20 mg x kg(-1). All the rats were given intragastric administration then blood samples were obtained from fossa orbitalis at several time points. All the plasmas concentrations were analyzed by HPLC method and the data were treated by DAS 2.0 program. RESULT: The main pharmacokinetics parameters of TMP 20 mg x kg(-1) group, ferulic acid 20 mg x kg( 1) and TMP 20 mg x kg(-1) + ferulic acid 20 mg x kg(-1) were as follows: t(max) 0.5 h, t1/2 0.856 h,MRT 1.321 h, AUC 5.112 microg x h(-1) x L(-1), C(max) 2.834 microg x L(-1); t(max) 0.083 h, t1/2 1.024 h, MRT 1.324 h, AUC 1.581 microg x h( 1) x L(-1), C(max) 1.492 microg x L(-1); t(max) 0.583 h, t1/2 37.901 h, MRT 3.798 h, AUC 4.097 microg x h(-1) x L(-1), C(max)1.571 microg x L(-1); t(max) 0.6 h, t1/2 7.860 h, MRT 2.894 h, AUC 1.984 microg x h(-1) x L(-1), C(max) 1.03 microg x L(-1), respectively. CONCLUSION: The experiments suggested that the compatibility of TMP and ferulic acid had interaction in pharmacokinetics; all the t1/2 and MRT were prolonged and had the effect of lente liberates. PMID- 20575397 TI - [Single and combining effects of Calculus Bovis and zolpidem on inhibitive neurotransmitter of rat striatum corpora]. AB - OBJECTIVE: To investigate the correlation effects between single or combined administration of Calculus Bovis or zolpidem and changes of inhibitive neurotransmitter in rat striatum corpora. METHOD: Sampling from rat striatum corpora was carried out through microdialysis. The content of two inhibitive neurotransmitters in rat corpus striatum- glycine (Gly) and gama aminobutyric acid (GABA), was determined by HPLC, which involved pre-column derivation with orthophthaladehyde, reversed-phase gradient elution and fluorescence detection. RESULT: GABA content of rat striatum corpora in Calculus Bovis group was significantly increased compared with saline group (P < 0.01). GABA content of zolpidem group and Calculus Boris plus zolpidem group were increased largely compared with saline group as well (P < 0.05). GABA content of Calculus Bovis group was higher than combination group (P < 0.05). GABA content of zolpidem group was not significantly different from combination group. Gly content of Calculus Bovis or zolpidem group was markedly increased compared with saline group or combination group (P < 0.05). CONCLUSION: Contents of two inhibitive neurotransmitters in rat striatum corpora were all significantly increased in Calculus Bovis group, zolpidem group and combination group. The magnitude of increase was lower in combination group than in Calculus Bovis group and Zolpidem group, suggesting that Calculus Bovis promoted encephalon inhibition is more powerful than zolpidem. The increase in two inhibitive neurotransmitters did not show reinforcing effect in combination group, suggesting that Calculus Bovis and zolpidem may compete the same receptors. Therefore, combination of Calculus Bovis containing drugs and zolpidem has no clinical significance. Calculus Bovis shouldn't as an aperture-opening drugs be used for resuscitation therapy. PMID- 20575398 TI - [Effect of emodin on P-gp expression in intrahepatic cholestatic rats]. AB - OBJECTIVE: To investigate the effect and mechanism of emodin on acute intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT) in rats. METHOD: Acute cholestatic model in rats was induced by ANIT. Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treatment were set up. Liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transport protein genes mdr1a (multidrug resistance protein 1a), mdr1b (multidrug resistance protein 1b) mdr2 (multidrug resistance protein 2), The expression of P-gp were determined by Western blotting analysis. RESULT: Compared to the model group, Emodin treatment resulted in significant reductions in serum total bilirubin (TBiL), direct bilirubin (DBiL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bile acid (TBA) (P < 0.01 or P < 0.05). By examining the liver pathology, it was found that hepatic cellular change and necrosis, inflammatory cell infiltration and bile duct proliferation were notably alleviated in emodin model with ANIT treatment. Analysis of gene expression in livers from emodin-treated cholestatic rats revealed that mdr1a, mdr1b and mdr2 could be up-regulated (P < 0.01 or P < 0.05), expression of P-gp was increased in accordance with its mRNA (P < 0.05). CONCLUSION: Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile-metabolism-related transporter P-gp in the liver to prevent bile acids and other toxic compounds overaccumulation in hepatocytes and hepatic toxicity. PMID- 20575399 TI - [Clinical study on effect of Shenfu injection treating cancer-related fatigue of patients with advanced carcinoma]. AB - OBJECTIVE: To study the effect of Shenfu injection (SF) treating cancer-related fatigue (CRF) of the patients with advanced carcinoma. METHOD: From September 2005 to June 2009, 113 patients with advanced carcinoma who was treated in our department were selected, and were divided into test group and control group. The test group was treated with SF and common method, while the control group only was treated with common method. Three weeks later, CRF, hemoglobin (Hb), immune function, cardiac function and blood viscosity were compared between the two groups. Meanwhile, the correlations between CRF and the other indicators were analyzed. RESULT: The test group was treated more effectively than the control group in some ways, such as relieving CRF, improving hemoglobin, some immune indicators, and cardiac function, and reducing blood viscosity. Moreover, CRF had negative correlation with Hb and cell-mediated immune, and had positive correlation with cardiac disfunction degree. CONCLUSION: SF could relieve CRF of the patients with advanced carcinoma effectively by treating anemia and improving cell-mediated immune and cardiac function. PMID- 20575400 TI - [Sheshiliuhuang decoction on cytokines in patients with urinary tract infection]. AB - OBJECTIVE: To investigate the therapeutic effects of Sheshiliuhuang decoction on clinical outcomes and cytokines in patients with urinary tract infection (UTI). METHOD: Ninety-two (92) patients were selected and randomly divided into 2 groups, the treatment group (n = 47) administered with Sheshiliuhuang decoction, one prescription, 2 times a day, while patients in the control group (n = 45) were given Sanjin pills, 3 pills a time, 3 times a day. The treatment lasted for 7 days. Clinical outcomes and serum levels of TNF-alpha, IL-6, IL-8 in both groups were examined before and after the treatment. RESULT: The clinical effective rate was 93.62% in the treatment group and 88.22% the control group, indicating a significant difference of P < 0.05. Before the treatment, the serum levels of TNF-alpha, IL-6, IL-8 of treatment group were significantly higher than those in the control group (P < 0.05). At the end of the treatment, serum levels of IL-6 and TNF-alpha in the treatment group were significantly decreased compared with the before treatment (P < 0.01) and those did in the control group (P < 0.01). CONCLUSION: Serum cytokines of IL-6, IL-8, and TNF-alpha were significantly increased in patients with UTI. Sheshiliuhuang decoction, with the mechanisms of regulating IL-6, IL-8, TNF-alpha, is an effective agent in patients with UTI. PMID- 20575401 TI - [Formation and development of toxicity theory of traditional Chinese medicine]. AB - The basic situation of formation and development of toxicity theory of traditional Chinese medicine in China was systematically summarized in this paper. A new "Network regulation theory" hypothesis about of toxicity of traditional Chinese medicine was firstly proposed and provided scientific bases for the clinic application of toxic traditional Chinese medicine. PMID- 20575402 TI - [Study on mechanism of precursors transforming into indigo and indirubin in blue genera plants]. AB - Accessed to literatures at home and abroad, we introduced the process of indigo naturalis transforming from dyestuff industry into pharmaceutical industry. It is affirmed that the precursors of indigo and indirubin are isatan A, isatan B, isatan C and indicant. Meanwhile, author clarified the mechanism of transformation for these precursors transforming into indigo and indirubin. And we summarized methods of determination for these precursors. In summary, these references provide us accordance of study on processing principle of Indigo naturalis, and lay the foundation for technics of making indigo and indirubin entering into modern industry. PMID- 20575403 TI - [Discussion about traditional Chinese medicine pharmacokinetics study based on first botanical drug approved by FDA]. AB - Pharmacokinetics study is one of main components of pharmaceuticals development. Food and Drug Administration (FDA) approved Veregen as the first botanical drug in 2006. This article introduced FDA's requirement on pharmacokinetics study of botanical drug and pharmacokinetics studies of Veregen, summarized current requirement and status quo of pharmacokinetics study on traditional Chinese medicine (TCM) and natural medicine in China, and discussed about pharmacokinetics study strategy for TCM and natural medicine. PMID- 20575404 TI - [Studies on phonological phases of cultivated Polygonatum]. AB - OBJECTIVE: To determine the phonological phases of cultivated Polygonatum by investigating the dynamic pattern of its growth and development, which would provide the guides for normal planting in the field. METHODS: Fix-point and real time observation combining with comprehensive survey were used in the field. RESULT: Cultivated Polygonatum had obvious processes of development including emergence of seedlings, extension of leaves, growth of stems and leaves, floral initiation, flowering, seed setting, death of plant-germinating-in-spring, plant shoot regeneration and hibernating shoot emergence, and hibernation with dead aerial part of plant. There were small differences in these processes of development among species and sites, but the whole phonological pattern hold relatively constant. CONCLUSION: The phonological phases of Polygonatum with eight stages, including seedlings emergence stage, plant extension stage, leaves extension stage, anthesis stage, seed stage, aerial part death stage, germination in-autumn stage, and hibernation stage, were finally determined. PMID- 20575405 TI - [Karyotype analysis of Gentiana straminea]. AB - OBJECTIVE: Study on chromosome number, karyotype of Gentiana straminea for the first time. Compare karyotypes of Gentiana straminea, Gentiana macrophylla and Gentiana dahurica. Provide cytological evidence for further studies on genetics and evolution. METHODS: Soak the root tip in 0.002 mol/L 8-oxychinolin solution for 5.7 h. Decomposed in 2.5% mixed enzyme solution for 1.6 h at 25 degrees C and use Hypotonic treatment for 3 h in refrigerator. At last, make specimen slides by the Air-drying technique. Sections combined with micrograph were used to analyze chromosome. RESULTS: The karyotypes formula of Gentiana straminea is K(2n) = 26 = 2M + 24 m, the AS. K was 52.68%, which belong to "1A" type. CONCLUSION: Compare karyotypes of Gentiana straminea, Gentiana macrophylla and Gentiana dahurica, the result showed that Gentiana macrophylla lives in highest stage of evolution. Gentiana straminea is intermediate between Gentiana macrophylla and Gentiana dahurica. PMID- 20575406 TI - [Study on the contents of flavonoids in Citrus reticulata 'Chachi' from various habitats and different collecting periods]. AB - OBJECTIVE: To determine the contents of hesperidin, nobiletin and tangeretin in Citrus reticulata 'Chachi' from various habitats and different collecting periods (from October to December) and study the dynamic change of three flavonoids constituents. METHODS: The HPLC method was used for analysis the contents of flavonoids in Citrus reticulata 'Chachi'. The system used a Diamonsil C18 column (250 mm x 4.6 mm, 5 microm) with gradient mobile phase of acetonitrile-methanol (80:20)-2% acetic acid. The monitoring wavelength was at 283 nm and 330 nm and the column temperature was at 25 degrees C with the flow rate of 1.0 ml/min. RESULTS: The contents of hesperidin, nobiletin and tangeretin in Citrus reticulata 'Chachi' collecting from various habitats descended gradually with the mature of fruit, especially in nobiletin and tangeretin. CONCLUSION: The method was simple, convenient and can be used to provide some foundation for the quality control of Citrus reticulata 'Chachi'. PMID- 20575407 TI - [Extraction and antihypertensive activity analysis of chondroitin sulfate from different animals]. AB - OBJECTIVE: Chondroitin Sulfate (CS) from different animals were extracted, which antihypertensive activities were compared. METHODS: CS from the bovine and chicken cartilages were extracted by diluted alkali-enzyme hydrolysis method, with removed free protein by Sevag method, separated and purified by quaternary ammonium complex. Their antihypertensive activities were tested by the modal of SPF rat. RESULTS: The extracted CS didn't have peptide, amino acid or other acid mucopolysaccharides determined by electrophoresis and chromatography, the results of IR was consisted with that of chondroitin sulfate supplied by Sigma Both BCCS and CCCS indicated the antihypertensive activities in the low dosage. Besides, BCCS had faster efficacy but shorter duration than that of CCCS. CONCLUSION: Both BCCS and CCCS had high purity. Animal experiments showed that BCCS and CCCS have the effect of the antihypertensive, which activity of CCCS was more significant than that of BCCS. PMID- 20575408 TI - [RAPD analysis on the germplasm resources of Baphicacanthus cusia]. AB - OBJECTIVE: To explore the genetic diversity of germplasm resources of Baphicacanthus cusia on molecular leve. METHODS: The molecular biological technique-random amplified polymorphic DNA (RAPD) were used. RESULTS: 104 random decamer primers were screened for RAPD fragments of Baphicacanthus cusia. 422 DNA bands were amplified by 12 primers, 55.69% products were found to be polymorphic. Base on UPGMA cluster analysis, a DNA molecular dendrogram was established to discuss the genetic diversity of the germplasm resources of Baphicacanthus cusia. The genetic differences are related to morphological differences on a certain extant, but not to geographic regions. CONCLUSION: There actually existed much genetic diversity on molecular level among different natural populations of Baphicacanthus cusia. PMID- 20575409 TI - [Studies on chemistry component and the biological activity of petroleum ether extraction from pre-and post-processed of Cornus officinalis]. AB - OBJECTIVE: To investigate substance basis for improving pharmacodynamics by comparing the chemical constituents of petroleum ether extraction from crude and processed Cornus officinalis and the effects on the immunologic function of mice with immunosuppression induced. METHODS: The volatile components in petroleum ether extraction were analyses by GC-MS. Non-specific immune function was determined by cleaning carbon particle index K, Swallow index a, spleen index and thymus index. The specific humoral immune function was evaluated by detecting the content of serum hemolysin. RESULTS: The chemical constituents of petroleum ether extraction of Cornus officinalis before and after being processed had significant changes. After being processed, Vitamin E increased by 46.6%, linoleic acid increased by 18.3% and methyl linen increased by 30.9%. The extraction increased clearance rate of charcoal carbon particles index K, swallow index alpha, spleen index, thymus index and the level of serum hemolysin. CONCLUSION: The extraction can markedly improve non-specific immune function and the specific humoral immune function which are active sites of improving immunologic function and post processed is better. Substance basis could be Vitamin E, Linoleic acid, methyl linen and so on. PMID- 20575410 TI - [Studies on HPCE fingerprint of Folium Apocyni Veneti]. AB - OBJECTIVE: To establish the analytical method for the fingerprint of Folium Apocyni Veneti by HPCE and estimate the quality of Folium Apocyni Veneti from different habitats. METHODS: Folium Apocyni Veneti from different habitats were analyzed and the chromatographic fingerprint were determined by HPCE. The data were analysed by Fuzzy Cluster and Fingerprint Similarity Evaluation Software to compare the similarity of samples. RESULTS: HPCE fingerprint of 7 main peaks was established preliminarily. It was discovered that a small number of samples differed from others. CONCLUSION: The method is reliable, accurate and can be used for quality control of Folium Apocyni Veneti. PMID- 20575411 TI - [Studies on the alkaloids from roots of Corydalis impatiens]. AB - OBJECTIVE: To study the alkaloids from Corydalis impatiens. METHODS: The alkaloids were isolated and purified by chromatography and their structures were identified by spectral data and others methods. RESULTS: Seven alkaloids were isolated and identified as bicuculline(1), ochotensine(2), ochotensimine(3), ochrobirine(4), tetrahydrothalifendine(5), norochotensimine(6), N methylactinodaphnine(7). CONCLUSION: All these compounds are isolated from this plant for the first time. PMID- 20575412 TI - [Isolation and identification of antineoplastic cyclic peptide]. AB - OBJECTIVE: To isolate and identify the antineoplastic constituents of the marine algae Galaxaura filamentosa. METHODS: The constituents were isolated and purified by low-pressure silica gel column chromatography, thin layer chromatography and recrystallization, and their structures were elucidated by spectroscopic analysis. RESULTS: Isolated a new antineoplastic cyclic peptide, cyclo-N-methyl Leucine-Leucine-N-methyl-Leucine-Leucine-Leucine. CONCLUSION: This new compound was remarkably active against the human renal cell carcinoma GRC-1 and human hepatocellular carcinoma HepG2 cell lines with corresponding IC50 values of 4.26 microg/mL and 4.63 microg/mL. PMID- 20575413 TI - [Study on the chemical constituents from pine needles of Cedrus deodara]. AB - OBJECTIVE: To study the chemical constituents from pine needles of Cedrus deodara. METHODS: Chemical constituents were isolated by silica gel and Sephadex LH-20 column chromatography. The structures of the isolated compounds were elucidated through spectroscopic analysis. RESULTS: The compounds were identified as 9-hydroxy-dodecanoic acid (I), ethyl laurate (II), ethyl stearate (III), 3beta hydroxy-oleanolic acid methyl ester (IV), beta-sitosterol (V), shikimic acid (VI), methylconiferin (VII), ferulic acid beta-glucoside (VIII). CONCLUSION: Compounds I-IV, VI-VIII are isolated and identified from this genus for the first time, compound V is isolated from pine needles of this genus for the first time. PMID- 20575414 TI - [Study on the flavonoids from Mosla chinensis 'jiangxiangru']. AB - OBJECTIVE: To study the chemical constituents of Mosla chinensis 'jiangxiangru'. METHODS: The chemical components were isolated and purified by silica gel and Sephadex LH-20 column chromatography. The chemical structures were elucidated on the basis of physic chemical properties and spectral data. RESULTS: Five compounds have been isolated from Mosla chinensis 'jiangxiangru'. On the basis of spectral analysis and physicochemical properties, the compounds were identified as negletein (I), luteolin (II), quercetin (III), chrysoeriol (IV) and apigenin (V). CONCLUSION: Compounds I-V are obtained from the genus for the first time. PMID- 20575415 TI - [Studies on the chemical constituents of extract with water from Forsythia suspensa]. AB - OBJECTIVE: To study the chemical constituents of the extract with water from Forsythia suspensa. METHODS: The compounds were isolated and repeatedly purified on TLC, silica gel column chromatograph, gel column chromatography, and preparative HPLC, and the structures were elucidated by physico-chemical properties and NMR. RESULTS: Eight compounds were obtained and elucidated as stearic acid(I), ursolic acid(II),p-hydroxyphenyl acetic acid(III),3-(4-ehtoxoy-3 hydroxyphenyl)acrylic acid(IV),isolariciresinol(V), epipinoresinol-4-O-beta-D glucoside(VI),(+)-epipinoresionl(VII),(+)-pinoresinol(VIII). CONCLUSION: Compound III is isolated from this genus for the first time. PMID- 20575416 TI - [GC-MS analysis of volatile constituents from Chinese eaglewood produced by artificial methods]. AB - OBJECTIVE: To study the volatile constituents from Chinese eaglewood samples produced by three different methods. METHODS: Essential oils of the three Chinese eaglewood samples were extracted with aether at room temperature. The chemical constituents and relative contents of the volatile oils were analyzed by GC-MS. RESULTS: The results showed that all the three volatile oils were mainly composed of sesquiterpenes, aromatic constituents, and fatty acids. CONCLUSION: The quality of the three Chinese eaglewood samples was evaluated by comparison of the characteristic constituents and their contents, of them, the quality of the Chinese eaglewood samples produced by methods of nail insetting and holing was better. PMID- 20575417 TI - [Analysis the chemical constituents of volatile oils in Medinilla arboricola by SPME-GC-MS]. AB - OBJECTIVE: To analyze the chemical constituents of the volatile oils in Medinilla arboricala. METHODS: The chemical constituents was extracted from Medinilla arboricola by SPME. The components of chemical constituents of volatile oil separated and identified by GC-MS. The relative content of each component was determined by area normalization. RESULTS: 60 kinds of components were separated and identified, accounting about 100% of the total chemical constituents. CONCLUSION: The main chemical constituents of Medinilla arboricola are D-Limonene (9.47%), [3R-(3a, 3aa,7a, 8aa]-octahydro-3,8, 8-trimethyl-6-methylene-1H-3a, 7 Metha noazulene (9.10%),3,4,5,6,7,8-hexahydro-4a, 8a-dimethyl-1 H-Naphthalen-2 one (6.15%), 1,4-Methano-1H-indene, octahydro-4-methyl-8-methylene-7-(1 methylethyl)-,[ 1S-(1a,3aa,4a,7a,7aa)] (5.58%), 1H-3a,7 Methanoazulene,2,3,4,7,8,8a-hexahydro-3,6,8,8-tetramethyl-[3R, (3a,3aa,7a,8aa)] (5.30%), 1H-3a,7-Methanoazulene,octahydro-3,8,8-trimethyl-6-methylene-[3R-(3a, 3aa,7a,8a)] (5.33%), Cyclohexene, 1-methyl-4-(5-methyl-1-methylene-4-hexenyl) ,(S)-(5.19%), Acetone (5.08%) etc. PMID- 20575418 TI - [Effects of Valeriana amurensis on the expressions of beta-APP, Abeta(1-40) and caspase-3 in Alzheimer's disease model rat's brain]. AB - OBJECTIVE: To investigate the effects of Valeriana amurensis on the expressions of P-APP,A4,1 and Caspase-3 of cortical neurons and hippocampus neurons in in Alzheimer's disease model rats' brain. METHODS: Established the model with multiple factors, observed the expressions of beta-APP, Abeta(1-40) and Caspase-3 of cortical neurons and Hippocampus neurons in in Alzheimer's disease model rats' brain by electron lens using immunohistochemistry method. RESULTS: The extracts of the roots and rhizomes of Valeriana amurensis decreased the expressions of beta-APP, Abeta(1-40) and Caspase-3 of cortical neurons and hippocampus neurons in in a dose-dependent manner. The effects of high dose of 50% ethanol extract of macroporous resin group were more significant than the other groups'. CONCLUSION: The 50% ethanol extracts of macroporous resin group from the roots and rhizomes of Valeriana amurensis can decrease the expressions of beta-APP, Abeta(1-40), and Caspase-3, to inhibit the formation of senile plaques and neurofibrillary tangles in Alzheimer's disease model rats' brain, and decrease cell fate of cortical neurons and hippocampus neurons in in Alzheimer's disease model rats' brain. PMID- 20575419 TI - [Effects of herba ephedrae, honey-fried herba ephedrae and maxingshigan decoction on autonomic activities of mice]. AB - OBJECTIVE: To discuss the significance of processing and complex prescription with Herba Ephedrae, the effects of Herba Ephedrae, Honey-fried Herba Ephedrae and Maxingshigan decoction on autonomic activities in mice were compared. METHODS: 110 female Kunming mice were divided into 11 groups, namely normal saline group (NS), ephedrine group (E), high dose Herba Ephedrae group (MH-H), moderate dose Herba Ephedrae group (MH-M), low dose Herba Ephedrae group (MH-L) ,high dose Honey-fried Herba Ephedrae group (ZMH-H), moderate dose Honey-fried Herba Ephedrae group (ZMH-M),low dose Honey-fried Herba Ephedrae group (ZMH-L), high dose Maxingshigan decoction group (MX-H), moderate dose Maxingshigan decoction group (MX-M) and low dose Maxingshigan decoction group (MX-L). The numbers of autonomic activity in 15 minutes before intragastric administration (ig), and after ig 0.5, 1, 2, 3, 4 h were determined. RESULTS: There was interaction between time and groups. There were very significant differences between before ig and all time-points after ig (P < 0.01). 30 minutes after ig,there were significant differences between E and NS,E and ZMH-L,E and MX-L (P < 0.05). 1 h after ig, there were significant differences between MX-M and NS (P < 0.05). 3 h after ig, there were significant differences between MX-M and MH-L (P < 0.05). 30 minutes after ig, both ZMH-L and MX-L could reduce the number of autonomic activity in some extent compare with MH-L. 1 h or 2 h after ig, ZMH-L could reduce the number of autonomic activity in some extent compare with MH-L 4 h after ig, MX-L could reduce the number of autonomic activity in some extent compare with MH-L. CONCLUSION: Under the condition of this study, regarding autonomic activity as index, both ZMH-L and MX-L can reduce center stimulation in some extent. PMID- 20575420 TI - [Hypoglycemic effect of extracts of cactus pear fruit polysaccharide in rats]. AB - OBJECTIVE: To study the hypoglycemic effect and mechanism of the extracts of cactus pear fruit polysaccharide (CPFP) in diabetic rats induced by streptozotocin (STZ). METHODS: The diabetic rats were induced by STZ in SD rats, and randomly divided into model group, insulin group,cactus pear juice group, high dose CPFP group,low dose CPFP group. The experimental rats were administrated for 8 weeks. During the experiment, the contents of blood glucose and blood limit of the rats were detected and body weight were recorded. The pathology of beta cell and alpha cell in pancreas of experimental rats were observed by immunohistochemistry. RESULTS: Compared with model group, the contents of blood glucose, total cholesterol and triglyceride were remarkably decreased in high and low dose CPFP groups. At the same time the body weight was significantly increased in high dose and low dose CPFP groups. The results of immunohistochemical stain demonstrated that the number of islet beta cells was increased and that of islet alpha cells was unchanged in the treatment groups. CONCLUSION: CPFP can markedly decrease blood glucose and blood limit in STZ induced diabetic rats. Its mechanism may be related to stimulating the secretion of insulin from beta cells. PMID- 20575421 TI - [Effect of formula for reinforcing kidney and activating blood on follicular development by rectal administration]. AB - OBJECTIVE: To study the effect of the Zichong Granules (ZG) on follicular development by rectal administration. METHODS: Underage rats and ovariectomized mice were administered with ZG by clyster perfusion. Diethylstilbestrol and Nvjindan (NJD) were taken as control. Ovarian follicle, corpus luteum of rats were counted. Uterus index and histomorphology of uterus of rats and mice were observed. In addition, E2 in blood of mice were determined by enzyme immunoassay (EIA). RESULTS: The effects of ZG, Diethylstilbestrol and NJD were similar. They all increased ovarian preantral follicles and total follicles of the rats (P < 0.01 or P < 0.05), uterus index and the thickness of endometrium of the rats (P < 0.05), and increased uterus index (P < 0.01),the thickness of endometrium (P < 0.05) and E2 level in blood (P < 0.05) of the mice. CONCLUSION: ZG administered by clyster perfusion can improve follicular development of underage rats, increase E2 level of ovariectomized mice, and present the estrogen-like effect. The effect of ZG for improving follicular development may be related to improving the level of E2. Rectal administration may be one of the effective ways to stimulate the follicular development. PMID- 20575422 TI - [Comparison of pharmacokinetics about ermiao capsules and ermiao pellet]. AB - OBJECTIVE: To compare the pharmacokinetics about Ermiao capsules and ermiao pellet, and observe the changes in plasma concentration with different formulations in animals from the perspective of pharmacokinetics. METHODS: After the rabbits were administered with Ermiao capsules and ermiao pellet through ig. HPLC was used to determine berberine in blood plasma at different times, DAS 2.0 procedure was used to process concentration-time data. RESULTS: In the rabbit plasma samples,the linear range of berberine was 0.00427-0.427 microg/mL, it has a high extract recovery rate,and day-day precision RSD was less than 10%. The whole blood concentration-time course of berberine in Ermiao capsules was fitted to be a two-compartment model, and berberine in Ermiao pellet was fitted to be a one-compartment model. CONCLUSION: This essay establishes a method for determine berberine in rabbit plasma, provided the pharma cokinetic parameters for rational administration of ermiao capsules, and also provided the pharmacokinetic study method of compounds. PMID- 20575423 TI - [Human osteoblast-like cells OS-732 intervened with alcohol and treated with liuweidihuang pill medicated serum]. AB - OBJECTIVE: To investigate the mechanism of osteonecrosis of the femoral head caused by alcohol and the therapeutic effects of the method of invigorating the kidney. METHODS: The osteoblast-like cells were intervened with 0.3, 0.9, 1.5 mol/L alcohol and observed by flow cytometry and light microscopy and electro microscopy. The cells intervened by 0.15 mol/L alcohol were treated with liuweidihuang pill medicated serum and observed by flow cytometry and light microscopy and electro microscopy. RESULTS: Apoptosis rate and the degree of cell necrosis had positive correlation with the concentration and the acting time of alcohol. The polymorphism of cells wer turned into roundness, and the cellular ecphyma was shortened and thinning, ribosome and endocytoplasmic reticulum were diminished. Part of the ruffle in mitochondria was disappeared. After treatment, the cellular ecphyma was recovered and the endoplasmic reticulum and golgi apparatus were visible. CONCLUSION: The osteoblast-like cells could be necrosis and apoptosis by the alcohol and were positive correlation with the intervened concentration and acting time. Chinese medicine with method of invigorating the kidney has effect on rehabilitating the cellular activity. PMID- 20575424 TI - [Investigation on the process of sapindus saponin purified with macroporous adsorption resin and screening of its bacteriostasis]. AB - OBJECTIVE: To study the technological parameters of the purification process of saponins with macroporous adsorption resin. METHODS: The adsorptive characteristics and elutive parameters of the process were studied by taking the elutive and purified ratio of saponins as markers. Bacteriostasis activity of each parts eluted was evaluated by the mean of cup-plate method. RESULTS: 13.6 mL of the extraction of sapindus saponin (crude drugs 0.01 g/mL) was purified with a column of macroporous adsorption resin (phi15 mm x H90 mm, dry weight 2.5 g) and washed with 3BV of distilled water, then eluted with 3BV of 30% ethanol and 3BV of 70% ethanol, most of saponins were collected in the 70% ethanol. CONCLUSION: With macroporous adsorption resin adsorbing and purifying, the elutive ratio of saponins was 93.8% and the purity reached 250.1%. So this process of applying macroporous adsorption resin to adsorb and purify saponins is feasible, and supplies reference to the purification of other types of saponin. PMID- 20575425 TI - [Process comparison of fingerprints of different extracts of Plumbago zeylanica by high performance liquid chromatography]. AB - OBJECTIVE: To optimize the separation conditions of fingerprints of Plumbago zeylanica by high performance liquid chromatography, on this basis, to choose the best way for extracting Plumbago zeylanica by high performance liquid chromatography. METHODS: The investigation of HPLC-FPs of the different extraction samples was by the retention time and the relative area of common peaks in fingerprints. RESULTS: We established the optimum separation conditions of HPLC-FPs for Plumbago zeylanica and there were 4 common peaks in fingerprints. According to the contrast research, the HPLC-FPs of the 90% ethanol extraction and SBE extraction of Plumbago zeylanica were quite similar, and they both had 9 common peaks in fingerprints, It was better to use SBE rather than WE in the extraction of Plumbago zeylanica. CONCLUSION: The SBE may replace the WE and ethanol extraction of Plumbago zeylanica. PMID- 20575426 TI - [Study on extraction of anti-diabetes active constituents from Potentilla chinesis]. AB - OBJECTIVE: To study the extraction technology of anti-diabetes active constituents from Potentilla chinesis. METHODS: Through single factor test, the effects of factors such as concentration of ethanol, temperature, ratio of liquid solid, extraction time and times of extraction were investigated. Through orthogonal experiment, the optimal conditions of extraction were obtained on the basis of single factor test. RESULTS: The optimum extraction conditions of Potentilla flavone from P. chinesis were determined as follows: refluxing for 3 times, 1.5 hours each time, and 8-6-6 for the multiple of 60% EtOH and material. CONCLUSION: The extraction process is stable and suitable for industry. PMID- 20575427 TI - [Comparison of flavonoids content in huangqi gnizhi wuwu tang of different dosages by uniform design method]. AB - OBJECTIVE: To determine the content of flavonoids in huangqi guizhi wuwu tang (HQGZWWT) of different dosages by uniform design method and analyze their difference for clinical application. METHODS: The uniform design set five factors and 11 levels to explore the content of flavonoids. The results were analyzed by computer with the method of multiple regression analysis. RESULTS: The contribution of each medicinal material to the content of total flavonoids was Radix Astragali (51.8%), Rhizoma Zingiberis (0.967%), Rhizoma Zingiberis (0.689%), Ramulus Cinnamomi (0.381%) and Raidix Paenoiae alba (0.185%), respectively. CONCLUSION: The extraction rate of flavonoids is not directly relative to the total amount of medicines, instead, there is an optimum dosage matching for it. PMID- 20575428 TI - [Induction and characterization of induced pluripotent stem (iPS) cells: a review]. AB - The somatic cells can be induced into ES-like stem cells when retrovirally infected the defined transcription factors including Oct4, Sox2, Klf4 and c-Myc. These ES-like cells are named induced pluripotent stem (iPS) cells and this method is called iPS technology. Until the end of 2009, iPS cell lines have been generated in various animal species, such as mouse, human, rhesus monkey, rat and pig. Mouse iPS cells are also used to generate chimera mice and viable mice through the tetraploid complementation. Although iPS cells are extremely similar to ES cells in both morphology and growth features, to generate iPS cells do need the defined culture procedures. Based on the update global iPS technology development and the iPS studies in our laboratory, this paper focused on the establishment of iPS cell lines and improvement of iPS cell culture condition. PMID- 20575429 TI - [Hepatitis B virus core protein as an epitope vaccine carrier: a review]. AB - Hepatitis B virus core (HBc) proteins have been used as carrier for foreign epitopes since the 1980s. They could self-assemble into icosahedral particles. Foreign epitopes could be inserted into HBc protein in various protein regions, including the N- or C-terminal and the major immunodominant region (MIR). The factors relevant in the design of HBc particles for vaccine purpose are summarized in this review. PMID- 20575430 TI - [Expression of porcine interferon-gamma and its safe antiviral assay]. AB - In order to ensure the biosafety of the IFN-gamma antiviral activity assay, we used a replication-deficient VSV carrying GFP as an interferon sensitive indicator virus (VSVdeltaG*G). The antiviral activities of porcine IFN-gamma expressed in Escherichia coli and in baculovirus on MDBK cells were assessed. The results showed that the antiviral activity of porcine IFN-gamma expressed in baculovirus could reach 10(5) IU/mL, while the porcine IFN-gamma expressed in E. coli showed some antiviral activity (32 IU/mL) after refolding. The results of the VSVdeltaG*G-based antiviral assay were almost identical to that of the VSV*GFP-based assay, suggesting it is highly feasible to use VSVdeltaG*G as a substitute for VSV*GFP, making assays for IFN-gamma antiviral activity safer and more accurate. PMID- 20575431 TI - [Construction and identification of recombinant retroviral vector of human ngn3 gene and its packaging cell line]. AB - In order to construct the recombinant retrovirus vector of human ngn3 gene and its packaging cell line, we successfully amplified the open reading frame (ORF) of ngn3 gene from human fetal pancreatic tissue by RT-PCR. The PCR products of human ngn3 gene was subcloned into pMD18-T vectors and sequenced. Results showed that its sequence was fully consistent with the ngn3 gene published in GenBank(GenBank Accession No. BC126468). The correct fragment was digested by EcoR I and Hpa I from recombinant pMD18-T vector and inserted into the same restriction enzyme sites of retroviral vector pMSCV-neo. We got recombinant retrovirus vector pMSCV-ngn3, which was identified by double restriction enzyme digestion and then transfected into PT67 cells by lipofectamine 2000. We established the PT67-ngn3 packaging cell line by G418 selection, which was detected by RT-PCR and immunohistochemistry staining. The detection results showed that the Ngn3 expressed at the mRNA and protein level in the packaging cell line. RT-PCR detection and electronic microscope analysis showed that the recombinant retroviral vector pMSCV-ngn3 was packaged into infectious virus particles and released into the supernatant of the cells. These results demonstrated that a PT67-ngn3 packaging cell line was successfully established, and this could facilitate the study of differentiation of the human fetal pancreatic progenitor cells into insulin-producing cells by using the ngn3 gene. PMID- 20575432 TI - [Fusion expression of Asia I type FMDV neutralizing epitope with heavy chain constant region of sheep IgG and the assessment of its immunogenicity]. AB - VP1 is a major antigenic protein of foot-and-mouth disease virus(FMDV), which induces the immune response against FMDV infection, and contains several epitopes of the virus. We designed and chemically synthesized a DNA fragment which encoding a tandem repeat protein of 136-160aa and 198-211aa of a strain of type Asia I FMDV, and cloned the gene of heavy chain constant region of sheep IgG. By using the BamH I, EcoR I and Xho I sites, both genes were cloned into pPROExHTb vector in turn to form a recombinant plasmid pPRO-FshIgG A chimeric protein, named FshIgG, was obtained after transforming the pPRO-FshIgG into Escherichia coli BL21 (DE3) host cell and induced by IPTG. Inoculation with 100 microg FsIgG induced strong neutralizing antibody response in guinea pigs, and FshIgG inoculated guinea pigs were also protected against 200 ID50 FMDV challenge. Our study indicated that the heavy chain constant region of sheep IgG can act as the carrier protein for FMDV peptide epitopes, and FshIgG is a potential multiepitope peptide vaccine candidate to prevent FMDV infection. PMID- 20575433 TI - [Construction of SOCS3 recombinant adenovirus and its expression in porcine primary adipocytes]. AB - In order to construct recombinant adenovirus vector expressing Suppressor of cytokine signaling 3 (SOCS3) and obtain infectious adenoviral particles, SOCS3 gene was amplified from plasmid pcDNA3-SOCS3 and subcloned into the adenovirus shuttle plasmid pAdTrack-CMV. After sequence confirmation, the recombinant shuttle plasmid pAdTrack-CMV-SOCS3 was linearized by Pme I, and then transformed into BJ5183 competent cell, the recombinant plasmid pAd-SOCS3 was obtained by homologous recombination between pAdTrack-CMV-SOCS3 and the adenoviral backbone plasmid pAdEasy-1 in BJ5183. The pAd-SOCS3 was linearized by Pac I and transfected into HEK293 cells via liposome. The recombinant adenovirus was packaged and amplified in HEK293 cells. After purifying, virus titer was determined by tissue culture infectious dose 50 (TCID50). Using the recombinant adenoviruses to infect porcine primary adipocytes, the expression of green fluorescent protein (GFP) was observed by fluorescent microscopy, and SOCS3 gene was identified by RT-PCR and Western blotting. Restriction enzyme and PCR analysis demonstrated that the recombinant adenovirus vector was constructed correctly, and the virus titer reached 1.2x10(9) PFU/mL. The result of RT-PCR and Western blotting showed that SOCS3 mRNA and protein expression was remarkably increased in porcine primary adipocytes infected with recombinant adenovirus. In conclusion, this study successfully constructed the recombinant adenovirus containing SOCS3 gene, and can be helpful for further research on the function of SOCS3. PMID- 20575434 TI - [Expression and biological function analysis of chicken aminopeptidase N]. AB - To clone and express the gene encoding chicken aminopeptidase N (chAPN), and analysis the biological function of chAPN expressed in Escherichia coli (E. coli). The chAPN gene was amplified by RT-PCR from the kidney cells of chicken embryo and then cloned into the prokaryotic expression vector pCOLD-TF. Recombinant expression plasmid of pCOLD-TF-chAPN was constructed and then transformed into the competent E. coli BL21(DE3) cells for expression under different conditions such as induction time and inductor concentrations. Purified soluble recombinant chAPN was obtained by Ni-NTA His Bind Resin affinity chromatography and identified by SDS-PAGE gel and Western blotting assay. Its biological function was detected by its reaction with Leu-PNA and Enzyme-Linked Immunosorbent Assay (ELISA). The results showed that the expression product of chAPN gene in E. coli was soluble. It was able to bind infectious bronchitis virus (IBV) dose-dependently. In conclusion, chAPN gene has been successfully cloned and expressed in E. coli, which will establish a basis for further research the enzymatic activity and antiviral function. PMID- 20575435 TI - [Influence of fusion protein of IBDV VP2 and chicken interleukin-2 on immune response in chicken]. AB - In order to research immunogenicity of the recombinant rVP2-IL-2 fusion protein, we obtained the rVP2-IL-2 fusion protein using Pichia pastoris expression system, and then evaluated its potential to induce immune responses in chicken. The effect was determined in the form of protective anti-IBDV VP2 titers, antibodies (IgG1 and IgG2a), lymphocyte proliferation, the levels of interferon-gamma and interleukin-4 cytokines, and challenge experiment. Antibody titers and proliferation lymphocyte level suggested that the fusion protein could elicit specific humoral immune and cellular immune responses, antibody sub-type results indicated that the rVP2-IL-2 fusion protein induced secretion both of IgG1 and IgG2a. The seem result elicited from cytokines ELISA test, secretion of both of Th1 (gamma-IFN) and Th2 (IL-4) were induced by the rVP2-IL-2 fusion protein. Challenge experiment result shown that chicken immunized the rVP2-IL-2 fusion protein obtained 85% protection. These results confirm that the fusion protein enhances the protection against IBDV through both humoral and cell-mediated immunity, and thus could serve as a candidate for the development of IBDV subunit vaccine. PMID- 20575436 TI - [Analysis of microbial diversity of nitrifying bacteria by terminal restriction fragment length polymorphism]. AB - We analyzed the microbial diversity and quantity of nitrifying bacteria in the enrichment reactor by Terminal Restriction Fragment Length Polymorphism (T_RFLP), a cultured-independent molecular technique. The result indicated that nitrobacteria enriched the best, and the diversity index decreased 62.80% compared with the initial data. Nitrobacteria were predominant in the reactor. Meanwhile, we studied the microbial diversity before and after adding Nitrobacteria into shrimp ponds, and analyzed several major bacterial species that existed stably in the pond. According to the analysis by T_RFLP program, species including Brevibacillus brevis, Microbacterium lactium, Azoarcus indigens and Bordetella holmesii were the dominant bacteria in the ponds. PMID- 20575437 TI - [Effects of nitrogen, manganese, and sulfur deprivation on photo-hydrogen evolution and growth of Chlorella pyrenoidosa]. AB - We studied the hydrogen evolution (HE) of green alga Chlorella pyrenoidosa grown in normal (nutrients sufficient) media and nitrogen, manganese or sulfur deprived medium. The results showed that photo-hydrogen evolution could occur under all conditions herein before, but the efficiency of HE was maximum under nitrogen deprivation, and the total hydrogen yield was 88.613 microL H2/mg Chla, which was 4.61, 1.92, 3.63 times of control, manganese deprivation, sulfur deprivation groups, respectively. We also measured the growth, the photosynthesis and respiration of the alga. The data demonstrated that manganese deprivation had less influence than nitrogen and sulfur deprivation on the growth, the photosynthesis and respiration of C. pyrenoidosa. Compared with the normal (nutrients sufficient), manganese and sulfur deprivation inhibited the photosynthesis and growth of the alga while bringing small impact on respiration. Nitrogen deprivation, however, greatly restrained the photosynthesis and growth while enhancing the respiration. Those data provide clues for the further study on both the conditions optimization and mechanism of hydrogen evolution. PMID- 20575438 TI - [Cloning, expression, purification of spinach carboxyl-terminal processing protease of D1 protein with hydrolysis activity and preparation of polyclonal antibody]. AB - Carboxyl-terminal processing protease of D1 protein (CtpA) catalyzes carboxyl terminal processing of the D1 protein of photosystem II, which is essential for the assembly of a manganese cluster and consequent light-mediated water oxidation. It is a target for the discovery of wide-spectrum herbicide. We amplified the CtpA gene from spinach cDNA with standard PCR method and constructed it into pET-28a vector to generate a recombinant expression plasmid. Recombinant CtpA fusion protein with His-tag was expressed as soluble protein in Escherichia coli BL21(DE3) after induction with 0.1 mmol/L IPTG at 8 degrees C for 72 h. We purified the CtpA protein with the Ni-NTA affinity chromatography and Superdex 75 gel filtration chromatography respectively, and verified the protein by SDS-PAGE and Western blotting with anti-his antibody. Hydrolysis activity of CtpA was assayed by HPLC method with a synthetic 24-mer oligopeptide corresponding to carboxyl terminal of precursor D1 protein, and gave a total activity of 1.10 nmol/(mg x min). We used the purified CtpA protein as antigen to immune rabbit for the production of polyclonal antibody, and prepared antibody with high specificity and sensitivity. The results obtained in this paper provided the feasibility of high-throughput screening of lead compounds for the protease as inhibitors and mechanism analysis of CtpA enzyme. PMID- 20575439 TI - [Kinetics of bioconversion of linoleic acid to conjugated linoleic acid by permeabilized Lactobacillus acidophilus cells]. AB - In this study, we analyzed the kinetics of bioconversion of conjugated linoleic acid (CLA) by permeabilized Lactobacillus acidophilus cells. The effects of cell mass, linoleic acid (LA) concentration, reaction pH and temperature on the bioconversion of CLA by permeabilized cells were investigated and the model system of bioconversion of CLA was established. The results showed that the production of CLA was increased by permeabilized cells. The optimal cell mass, pH and temperature of bioconversion of CLA were 10 x 10(10) ufc/mL, 4.5 and 45 degrees C, respectively. A marked LA inhibition phenomenon existed, and the early reaction rate of producing CLA reached the maximum (17.8 microg/mL x min) when LA concentration was 0.6 mg/mL. Michaelis constant was obtained by double-reciprocal plot and Hanes-Woolf plot. The reaction rate equation followed the classic Michaelis-Mentent equation at the low LA concentration, while there was a marked LA inhibition phenomenon at the high LA concentration. With the evaluated model parameters, the model system appeared to provide a description for the bioconversion of CLA by permeabilized Lactobacillus acidophilus cells. PMID- 20575440 TI - [Cloning, expression and characterization of a gene encoding alpha2 subunit of the proteasome in Schistosoma japonicum]. AB - The 26S proteasome is a proteolytic complex responsible for the degradation of the vast majority of eukaryotic proteins. Regulated proteolysis by the proteasome is thought to influence cell cycle progression, transcriptional control, and other critical cellular processes. A novel Schistosoma japonicum gene (GenBank Accession No. AY813725) proteasome alpha2 subunit (SjPSMA2) was cloned. Sequence analysis revealed that the ORF of SjPSMA2 gene contains 708 nucleotides encoding 235 amino acids, and the molecular weight was estimated to be 25.84 kDa. Real time PCR analysis showed that this gene expressed in 7 d, 13 d, 18 d, 23 d, 32 d and 42 d schistosoma. The mRNA level of SjPSMA2 was lower in 7 d and 23 d schistosomulum than that in other stages. The SjPSMA2 cDNA fragment was subcloned into an expression vector pET28a(+) and transformed into E. coli BL21 (DE3) cells. After induction with IPTCQ the 30 kDa fusion protein was produced as included bodies. Western-blotting revealed that the fusion protein could be recognized by the rabbit serum anti-Schistosoma japonicum adult worm antigen preparation, and the protein in native could be detected. After immunization of BALB/c mice with the fusion protein, the reduction rates of worm counts and liver egg counts were 12.33% and 35.23%. ELISA results revealed that the vaccinated group showed a significant increase in the level of IgG antibody. This study provided an important basis for investigating the regulation mechanism of the proteasome during the development of Schistosoma japonicum. PMID- 20575441 TI - [Expression and purification of lysin B in mycobacteriophage D29 and analysis of its enzymatic properties]. AB - LysinB (LysB) in mycobacteriophage D29 was cloned and expressed and its enzymatic properties were analysed. The lysB gene was amplified by PCR from mycobacteriophage D29 genomic DNA and inserted into pET22b vector. The constructed recombinant plasmid was transformed into Escherichia coli BL21(DE3) to express fusion protein, which was purified by Ni-NTA column and enzymatic activity detected. The results showed that expression plasmid pET22b-lysB was constructed successfully. Highly purified recombination protein (His-LysB) was obtained 33.2 mg from 1 L LB culture medium. A screening for His-LysB activity on esterase and lipase substrates confirmed the lipolytic activity. With p nitrophenyl butyrate as substrate, the thermal stability of the enzyme was poor when the temperature was above 30 degrees C. The enzyme exhibited higher stability at pH 5.0-9.5. The optimum temperature and pH for the lipolytic activity of His-LysB were 23 degrees C and 7.5 respectively. Under the optimum conditions, the specific activity of His-LysB was 1.3 U/mg. Zn2+, CU2+, Mg2+, Mn2+ and phenylmethane sulfonyl fruoride severely inhibited the lipolytic activity of His-LysB. The result provides a new option for tuberculosis drug research and development. PMID- 20575442 TI - [High-level expression and antimicrobial activity of recombinant N-terminal porcine lactoferrin]. AB - Lactoferrin in milk is a multifunctional protein. In addition, lactoferrin has antiviral, antifungal and antiparasitic activity. In this study, the N-terminus from porcine lactoferrin (PLF-N) was designed to express the antimicrobial action of recombinant porcine lactoferrin. We cloned a 1077 bp fragment of the PLF gene from mammary gland tissue of the lactating sow at the third day. Comparing nucleotide sequence with four strains of PLF gene published on GenBank, the homology was more than 99%. With the reference template of the cloned fragment of PLF-N and optimizing codon bias, we synthesized the gene of N-terminus encoding porcine lactoferrin (PLF-NS). The high expression gene of PLF-NS was cloned into the fusion expression vector pET30b and expressed in E. coli BL21 (DE3). After induced with Isopropyl beta-D-1-Thiogalactopyranoside (IPTG), the target fusion protein was successfully expressed and identified in inclusion bodies by SDS-PAGE and Western blotting. The protein had a molecular weight of 42 kDa and accounted for 32% of the total cellular protein. After purification and renaturation, the purity of the expressed protein was 98%. The expressed PLF-NS protein showed obviously antibacterial activity. This method provides an excellent way for high expression of antimicrobial proteins when optimizing codon bias. PMID- 20575443 TI - [Differentiated expression of VvSUC12 and VvSUC27 in embryogenic and non embryogenic calli of Vitis vinifera L]. AB - We induced embryogenic calli (EC) and non-embryogenic calli (NEC) from flower filaments of Vitis vinifera L. cv. Chardonnay about 10 days before full bloom. The callus were sub-cultured, observed and verified by somatic embryo induction. PCR primers for VvSUC12 and VvSCU27 were designed according to the corresponding sequences in GenBank. After RNA extraction with RNAplant for EC and NEC cell lines, we synthesized the 1st strand DNA for semi quantitative RT-PCR, and normalized the density of the bands against house-keeping gene Actin. The results of 31 cycles semi-quantitative RT-PCR showed that VvSUC12 was highly expressed in both EC and NEC, with higher expression intensity in NEC than in EC, but not reached the significant level; while the expression of VvSUC27 was only detected in EC, and the expression level was significantly lower than that of VvSUC12. We increased the semi-quantitative RT-PCR cycle number to 35 and found that VvSUC27 gene was weakly expressed in NEC, in EC the intensity of the band was increased comparing with 31 cycles, and the expression level was higher than that of NEC. The paper discussed the differential expression of the two sucrose transporters and their relationship with the sucrose in the tissue culture medium. PMID- 20575444 TI - [Expression, purification and activity determination of cyanovirin-N]. AB - Cyanovirin-N (CVN) is an 11 kDa anti-HIV protein originally isolated from extracts of a cyanobacterium, Nostoc ellipsosporum. The protein binds with high affinity to the viral envelope glycoprotein gp120 and irreversibly inactivates diverse HIV strains. A fusion gene consisting of cvn, sumo and 6xHis tag was synthesized by PCR according to the codon bias of Escherichia coli. The fusion protein is expressed in the cytoplasm of E. coli in a soluble form and up to 28% of the total protein. The recombinant CVN was purified to homogeneity by 2 rounds of Ni-NTA affinity chromatography and one round of SUMO protease cleavage. Bioactivity assay demonstrated that SUMO-CVN and CVN bound to gp120 with nanomolar concentration. In addition, CVN showed potent anti-HSV-1 and anti-HIV-1 activities in in vitro cellular assays. Therefore, the 6xHis SUMO fusion expression and purification system provides a better approach for large scale production of CVN for further microbicide development. PMID- 20575445 TI - [Preparation and properties of SiO2 tubes immobilized antibody for HCAg detection]. AB - In order to optimize the fabrication of SiO2 tubes immobilized with antibody for hepatitis C virus antigen (HCAg) detection, we formed the activated amino on the surface of SiO2 tubes by using the activation of aminosilane. Then we immobilized the hepatitis C virus (HCV) monoclonal antibody on the surface of SiO2 tubes by using glutaraldehyde as a chemical cross-linker, followed by detecting HCAg. Sequence tests showed that when the SiO2 tubes were treated in 10% (V/V) aminosilane solution and 3% (V/V) glutaraldehyde solution for 3 hours and 2 hours, respectively, the HCV monoclonal antibody had high immobilization efficiency and low nonspecificity, and the HCAg was detected to 1 ng/mL. This experiment can provide principle and experimental data for establishment of HCAg magnetic immunoassay system. PMID- 20575446 TI - [Designation, solid-phase synthesis and antimicrobial activity of Mytilin derived peptides based on Mytilin-1 from Mytilus coruscus]. AB - As a key role in mussel defense system, Mytilin is an important antibacterial peptide isolated from the mussel serum. The structural and functional researches on Mytilin showed that the fragment connecting two beta-sheets in a stable beta hairpin structure was probably required for antimicrobial activity. To elucidate the structural features and the antimicrobial activity of this fragment, we re designed and synthesized two peptides corresponding to the main mimic structures of Mytilin-1 from Mytilus coruscus, we named these two peptides Mytilin Derived Peptide-1 and Mytilin Derived Peptide-2, respectively. Using a liquid growth inhibition assay, we evaluated their activity towards Gram-positive, Gram negative bacteria and fungus. The results showed that both peptides can inhibit the growth of Gram-positive, Gram-negative bacteria and fungus. Besides, these two peptides showed high stability in heat water and human serum. These works laid the foundation for further research on the molecular mechanism of Mytilin and for further exploitation of antibacterial peptides with lower molecular mass and more stable structure. PMID- 20575447 TI - Human resources. Responsibilities of redundancy. PMID- 20575448 TI - Technology. Access some online ingenuity. PMID- 20575449 TI - No prospects for MSD column. PMID- 20575450 TI - No fear safety leadership. PMID- 20575451 TI - Safe harbor. PMID- 20575452 TI - Different domains. PMID- 20575453 TI - The folly of safety training: a fable about influence. PMID- 20575454 TI - Climbing the cognitive learning ladder. PMID- 20575455 TI - Grainger gets serious about services. PMID- 20575456 TI - Trends in glove manufacturing. PMID- 20575457 TI - Z87.1-2010 takes a new approach. PMID- 20575458 TI - Make it possible to save every employee. PMID- 20575459 TI - Choosing the right manikin for the job. PMID- 20575460 TI - [Guidelines, 1, 2,3]. PMID- 20575461 TI - [Treatment of patients with unipolar depression. Summary of the S3 guidelines/National Care Guidelines "Unipolar Depression"]. PMID- 20575462 TI - [Epilepsies and their medical treatment]. AB - During the last decade, medical treatment of epilepsies has not progressed a lot regarding its efficacy, but options have widened considerably. Second generation antiepileptic drugs (AED) have advantages in pharmacokinetics, show an overall better tolerability as compared to old AED, and use new mechanisms of action. This offers the opportunity to invidualization of patient treatment. Whereas several drugs released since 2000 have already established their role in differential treatment of epilepsies, the role of new substances like lacosamide, eslicarbazepine, and retigabine will become clear during the years to come. Presently, new antiepileptic drugs play a key role in the initial treatment of epilepsies, in difficult-to-treat epilepsy syndromes, and recently also in intravenous epilepsy treatment. These treatment options have emerged not only in monotherapy, but also in combination therapy, where the lower tendency of interactions in new antiepileptic drugs like lacosamide, levetiracetam, pregabalin, and zonisamide offers particular advantages. PMID- 20575463 TI - [SSRI-associated bleeding risk]. AB - Secondary to their antidepressive effect, selective serotonin reuptake inhibitors (SSRI) also lead to a diminished platelet aggregation, which results in an increased risk of bleeding. This adverse effect is added to the therapeutic effects of antiplatelet drugs. Furthermore, combination with nonsteroidal antirheumatic drugs (NSAID) increases the risk of bleeding, particularly in the gastrointestinal tract. Given the widespread use of SSRI, antiplatelet drugs and NSAID, pharmacists and doctors should turn their attention to bleeding as adverse effect and interaction, respectively. PMID- 20575464 TI - Comparison of two different screening methods for the KRAS mutation in colorectal cancer. AB - BACKGROUND: To compare high resolution melting (HRM) and primer extension (PE) for mutation screening of KRAS codons 12 and 13. METHODS: DNA samples were isolated from 60 colorectal cancer (CRC) patients. HRM and primer extension analyses were used for mutation screening of KRAS codons 12 and 13. RESULTS: Both methods can detect KRAS mutations in a DNA mixture containing as little as 5% mutant DNA. The concordant rate between the two methods was 100%. HRM analysis is able to distinguish mutant from wild type, however, it is unable to detect the actual base change. PE analysis needs more procedures, is time-consuming and slightly more expensive but it is able to detect the precise mutation. CONCLUSIONS: This study showed that HRM is a reliable screening method to identify mutations in the KRAS gene, and the PE can be used as a diagnostic method to accurately pinpoint the nature of mutations. PMID- 20575465 TI - Type 2 diabetes mellitus without vascular complications and ischemia modified albumin. AB - Ischemia modified albumin (IMA) is a proven cardiac marker but its role in type 2 diabetes mellitus without vascular complications has not been reported yet. Therefore, IMA was estimated in 60 newly diagnosed patients of type 2 diabetes mellitus and 30 healthy controls along with HbA1c and other investigations (to rule out vascular complications). There was no significant change in IMA levels in type 2 diabetic patients as compared to controls. No correlation could be found between IMA levels and HbA1c. We conclude that IMA levels are not affected in type 2 diabetes mellitus before the onset of vascular complications. PMID- 20575466 TI - Serum fetuin A concentrations in patients with acute pancreatitis. AB - BACKGROUND: Acute pancreatitis (AP) is a mild and self-limiting disease in most patients, but necrotizing pancreatitis develops in up to 20 - 30% of the cases. Early recognition of severe AP has been considered as a key determinant of successful therapy. The aim of this study was to evaluate the clinical value of fetuin A as the new predictor of complications and fatal outcome during acute pancreatitis (AP). METHODS: The study included 40 patients with AP of diverse severity (28 mild, 12 severe), assessed during the early phase of AP (1st - 7th day of hospitalization). Fetuin A level was measured by ELISA kit (BioVendor). RESULTS: Median serum fetuin A concentrations had a tendency to decrease during examination from 0,371 g/L at admission to 0,288 g/L on the 7th day of hospitalization. In each of 7 days of observation, correlation between the increase in fetuin A and the absolute number of RBC was found (R = 0,34: 1st day R = 0,35: 3rd day, p < 0,05; R = 0,57: 5th day, p < 0,001; R = 0,65: 7th day, p < 0,01). Additionally, we observed the reverse relationship between the decrease in fetuin A and the increase in some inflammatory markers (IL-6: R = -0,61, p < 0,0001; SAA: R = -0,58, p < 0,001; HGF: R = -0,60, p < 0,01; PCT: R = -0,475, p < 0,01). The strongest positive correlation was noticed on the 5th day of hospitalization between decreased levels of fetuin A and albumin (R = 0,83; p < 0,0001). CONCLUSIONS: Fetuin A level monitoring is potentially a new marker for non-invasive and accurate prediction status for the hospitalization of patients with AP similar to other negative acute phase proteins like albumin. PMID- 20575467 TI - Evaluation of two immunoassays for the measurement of human chorionic gonadotropin in urine for anti-doping purposes. AB - BACKGROUND: Urinary human chorionic gonadotropin (hCG) concentration is routinely measured in all anti-doping laboratories to exclude the misuse of recombinant or urinary hCG preparations. In this study, extended validation of two commercial immunoassays for hCG measurements in urine was performed. Both tests were initially designed for hCG determination in human serum/plasma. METHODS: Access and Elecsys 1010 are two automated immunoanalysers for central laboratories. The limits of detection and quantification, as well as intra-laboratory and inter technique correlation, precision, and accuracy, were determined. Stability studies of hCG in urine following freezing and thawing cycles (n = 3) as well as storage conditions at room temperature, 4 degrees C and -20 degrees C, were performed. RESULTS: Statistical evaluation of hCG concentrations in male urine samples (n = 2429) measured with the Elecsys 1010 system enabled us to draw a skewed frequency histogram and establish a far outside value equal to 2.3 IU/L. This decision limit corresponds to the concentration at which a sportsman will be considered positive for hCG. Intra-assay precision for the Access analyser was less than 4.0%, whereas the inter-assay precision was closer to 4.5% (concentrations of the official external controls contained between 5.5 and 195.0 IU/L). Intra and interassay precision for the Elecsys 1010 analyser was slightly better. A good inter-technique correlation was obtained when measuring various urine samples (male and female). No urinary hCG loss was observed after two freeze/thaw cycles. On the other hand, time and inappropriate storage conditions, such as temperatures above 10 degrees C for more than 5 days, can deteriorate urinary hCG. CONCLUSIONS: Both analysers showed acceptable performances and are suitable for screening urine for anti-doping analyses. Each laboratory should validate and establish its own reference values because hCG concentrations measured in urine can be different from one immunoassay to another. The time delay between urine collection and analysis should be reduced as much as possible, and urine samples should be transported in optimal conditions to avoid a loss of hCG immunoreactivity. PMID- 20575469 TI - Utility of placental growth factor for prediction of 30-day adverse event in emergency department population with non-ST elevation acute coronary syndrome. AB - BACKGROUND: Placental growth factor (PIGF) belongs to the vascular endothelial growth factor family and seems to be an independent biomarker for plaque disruption, ischemia, and thrombosis. Plasma PIGF is rapidly produced in infarcted myocardial tissue during the acute phase of myocardial infarction. In this study, the relevance of PIGF was analyzed at the admission of patients with acute coronary syndrome (ACS) without ST elevation for the prognosis of fatal outcome after 30 days. METHODS: We collected blood samples from 102 ACS patients admitted to the coronary unit with manifesting acute chest pain within the previous 12 hours and measured the levels of PIGF, high-sensitivity C-reactive protein (hsCRP), and cardiac markers: troponin T (cTnT), B-type natriuretic peptide, creatine kinase-MB (CKMB) and CK activity. RESULTS: PIGF, troponin T, and hsCRP levels were significantly higher in non-survivors than in survivors. ROC analysis showed that PIGF had the highest area under ROC curve (AUC, 0.713), but it was not significantly different from AUCs for cTnT and hsCRP. Higher values of PIGF (>13.2 ng/L) pointed towards a higher risk of fatal outcome (HR 2.28; 95 % CI 1.21-4.76; P=0.0125). The multivariable proportional hazards analysis, which had involved other statistically significant markers of relative risk (age and gender), showed that PIGF was an independent prognostic marker (adjusted HR 2.14; 95 % CI 1.08-4.22). CONCLUSIONS: These results confirmed that PIGF is an independent biomarker of short-term adverse outcome in patients with ACS without ST elevation and that plaque instability, represented by PIGF elevation, has an important role in the pathogenesis of future coronary events. PMID- 20575468 TI - Antioxidant defense in patients with chronic viral hepatitis B and C type. AB - BACKGROUND: The aim of the present study was to determine erythrocyte glutathione, superoxide dismutase, catalase, glutathione peroxidase, and serum total antioxidant response levels in a large chronic viral hepatitis group who had no antiviral treatment, and also the relationship of these parameters with viral load, fibrosis score, and necro-inflammation of the liver. METHODS: 200 patients who were diagnosed with chronic viral hepatitis and 107 healthy subjects were included in this study. Antioxidant parameters were measured spectrophotometrically. The viral load was assayed using a polymerase chain reaction technique. Histopathologic findings in the liver were scored as necro inflammatory activity and fibrosis according to Ishak-Knodell score. RESULTS: Erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, glutathione, and serum total antioxidant response levels were significantly lower in patients than in controls (p < 0,001). Additionally, no significant correlation was found between these markers and viral load, necro-inflammation, and fibrosis of the liver in patients with chronic viral hepatitis. CONCLUSIONS: Our data suggest the insufficiency of an antioxidant barrier in patients with chronic viral hepatitis, but the decrease in antioxidant systems was not correlated with viral load, necro-inflammatory activity, and fibrosis score in the liver. PMID- 20575470 TI - Nonspecific biochemical changes under different health statuses and a quantitative model based on biological markers to evaluate systemic function in humans. AB - BACKGROUND: To investigate the markers of systemic function by using laboratory parameters as life parameters. METHODS: Lymphocyte count, albumin, and creatinine levels were measured using automatic analyzers in young, healthy individuals (20 39 years) and senior individuals (80-95 years) as well as in terminally ill patients. We developed a mathematic model and scoring system (indexes of systemic function, ISF) based on the above mentioned biological markers. RESULTS: ISF scores were significantly lower in the senior group (P < 0.05) than those in the young, healthy group. A significant decrease was observed in the ISF of the terminally ill group and that of the senior group (P < 0.05). CONCLUSIONS: Our results suggest that the ISF scoring system of systemic function can be used to objectively evaluate the systemic function in individuals with different health statuses. PMID- 20575471 TI - Serum glucose- and C-reactive protein-based assessment of stress status in a healthy population. AB - BACKGROUND: The purpose of the present study is to develop a quantitative system that will allow objective assessment of a stress gradient and to examine the relationship between stress and health. METHODS: The stress group consisted of patients with fractures. The low stress group consisted of strong manual workers, mental workers, and those who had experienced stressful social events. The subjects in the control group were healthy. We measured the levels of 2 laboratory parameters--high sensitive C-reactive protein and fasting plasma glucose--using automated analyzers. The above-mentioned two indicators were transformed into quailtative indicators based on the median value derived from the healthy population (values above and below the median value were designated as positive and negative, respectively). Apart from one person who was positive for both indicators and was thus considered positive for stress, the remaining individuals were all negative for stress. RESULTS: The positive rates of stress were 82.4% and 39.8% in the stress group and low stress group respectively. These values were significantly different from control group (P <0.05). CONCLUSIONS: We have successfully developed a simple, precise, and sensitive method for the quantification of stress. PMID- 20575472 TI - The study of the Golgi apparatus in blood--basic science and clinical applications. AB - The Golgi apparatus (GA) is a cytoplasmic organelle that is of great interest to all scientists for its key role in the biosynthesis, transporting and sorting of both lipids and proteins located at the intersection of the secretory and endocytic pathways. Recently, more and more evidence shows that changes in the Golgi apparatus play an important role in the clinical progression and pathological development of many diseases. In this review, we will summarize the alteration of the Golgi apparatus in blood cells and anti-Golgi complex antibodies in blood serum under different conditions and further clarify the contribution of the Golgi apparatus dysfunction to the course of these diseases and its pathophysiological basis, which will significantly improve our understanding and impact our ability to develop more effective therapies for these diseases. PMID- 20575473 TI - Thromboembolic risk assessment in a phenotypically cured factor-V-Leiden carrier after orthotopic liver transplantation. AB - BACKGROUND: The factor V Leiden mutation is a common genetic risk factor for thromboembolism. After liver transplantation, patients may present with an acquired factor V phenotype - genotype discrepancy. CASE REPORT: We present the history of a heterozygous carrier of the factor V Leiden mutation who needed liver transplantation because of coumarin-induced acute liver failure. This led to a phenotype - genotype discrepancy with apparent cure from the factor V Leiden carrier status. CONCLUSIONS: To date the thromboembolic risk assessment regarding the need for postoperative prophylactic anticoagulation in such patients has remained controversial with respect to the intracellular fraction of factor V in platelets. However, recent observations have shown that platelet factor V Leiden is endocytosed by megacaryocytes from plasma. Therefore, former assessments of an ongoing risk for thromboembolic events despite apparent cure of the factor V Leiden carrier status after liver transplantation should be corrected. PMID- 20575474 TI - [2010 Cape Town ICLAM retrospect]. PMID- 20575475 TI - [Evidence based risk assessment of coronary heart disease]. AB - Coronary heart disease (CHD) poses a special challenge for risk assessments. Various kinds of diagnostic or therapeutic procedures, concomitant diseases, risk factors and symptoms need to be connected logically in order to assess the risk of each individual applicant. "Reinsurance manuals" are available to risk assessors in life insurance for this purpose. Using these manuals, the risk assessor can calculate the risk loadings for applicants with specific pre existing conditions, e.g., CHD. Various tasks thus fall to the reinsurer, which must be able to give grounds for the increased risk loadings, provide the manuals with a process-oriented structure and simultaneously support the primary insurer's business objectives via an intelligent risk assessment. Taking CHD as an example, the following article explains how these tasks can be solved with the aid of medical and mathematical approaches, and how the insurability of applicants with CHD can be extended via the re-evaluation of risks. PMID- 20575476 TI - [Return to work after heart transplantation]. AB - Heart transplantation is the most effective treatment option for patients with end-stage heart failure to improve exercise tolerance and quality of life. This increase in quality of life may assume that heart transplant recipients are also able to return to their work. In general, there are no medical reasons to oppose a return to work. Despite enormous advances in medical rehabilitation after heart transplantation, the rate of working people among heart transplant recipients is very low. According to a survey at the Heidelberg Heart Transplant Center, only 37% of the heart transplant recipients return to work. This may be caused by tranplant-related problems as well as factors independent of heart transplantation. Furthermore, the psychological burden due to heart transplantation might hamper professional rehabilitation. Thus, psychotherapeutical support during transplant process appears to be appropriate. As a major issue for a return to work appears to be the patient's will, the voluntary nature of return to work step by step has to be limited. Programmes with close collaboration between physicians, health insurance companies, retirement insurance companies, employers, and especially the patients are necessary to increase the rate of professional rehabilitation and to underscore the health economic justification of heart transplant programmes. PMID- 20575477 TI - ["Liver enzymes"--interpretation of laboratory values]. AB - Measurement of the alanine aminotransferrase-(ALT) and aspartate aminotransferase (AST) activity in the serum has been used to identify patients with liver disease for more than 50 years. While isolated moderate to strong elevations of ALT and AST typically indicate specific liver disease, mild elevations of aminotransferases can be observed in widespread diseases, e.g., metabolic syndrome. Various studies were able to show an association between elevated liver enzymes and liver associated mortality as well as overall mortality. Aminotransferase values in the general population vary with gender, age and ethnicity and studies show that current broadly applied upper limits of normal for ALT and AST are unreliable for sensitively detecting or excluding significant liver disease. However, the measurement of these liver enzymes remains an important tool in the official diagnostic & treatment decision process. PMID- 20575478 TI - [Risk factors for invalidity in psychiatric disorders--development of an empirically based assessment tool]. AB - The staggering amount of health-related disability associated with psychiatric disorders is increasing medical claim costs. Government-run health systems and social health insurances are under pressure in almost every developed country. The complex interrelationship of these disorders and disability pensioning poses a number of challenges and emphasises the need for specialists in psychiatric medicine. In the past, physicians did not favour standardised expert testimonies because it often limits a physician's freedom to decide. In this study an empirically based assessment instrument was developed to predict the final outcome, with respect to future disability. Further prospective clinical research should aim to differentiate subjects with "high risks" from those with a better prognosis. PMID- 20575479 TI - [Indication criteria for stationary psychosomatic treatment]. AB - In consideration of the existing possibilities in Germany, the author discusses the indication criteria and the duration of stationary psychosomatic treatment. Aside from the general criteria for hospitalisation, the traditional bio-psycho social model of illness is emphasized as an important basic principle, to include social factors in the indication criteria for stationary psychosomatic treatment. Adjacent, backgrounds for the decision between a regional and a regionally distant treatment are proposed. PMID- 20575480 TI - [The "sunshine" state--a utopia? (II). Historical welfare plans between dream and reality in the present time]. PMID- 20575482 TI - [Alternative medicine treatment of periodontitis in a naturopathy center]. PMID- 20575483 TI - [Implant acupuncture]. PMID- 20575484 TI - Data-driven. HHS unleashes wave of public health data so software developers can create tools to raise awareness, spur action. AB - Guided by how weather data from the National Oceanic and Atmospheric Administration fuels all kinds of weather reports, maps and forecasts, HHS officials saw parallels on how to distribute health data so software developers could create tools to be used by patients and providers. "We thought that was inspiring," said Todd Park, left, HHS' chief technology officer. PMID- 20575485 TI - Deal talk hurts Tenet. Healthscope in Australia gets three competing offers. PMID- 20575486 TI - Prevention defense. Service providers must pitch in to help cash-strapped local health departments. PMID- 20575487 TI - It's all relative. New RRU measures to help assess health plan value. PMID- 20575488 TI - Organisms in their milieu: Alfred Giard, his pupils, and early ethology, 1870 1930. AB - This essay tells the story of early French ethology--"the science dealing with the habits of living beings and their relations, both with each other and with the cosmic environment." The driving force behind this "ethological movement" was the biologist Alfred Giard (1846-1908). The essay discusses how the ethological viewpoint of Giard and his pupils developed in a period in which the current disciplines of field biology were not yet crystallized. It also shows how concepts and research interests could travel within Giard's network from one working context to another, even from one discipline to another. By studying this traveling process, the essay reveals that, unlike the modern ethology of Konrad Lorenz and Niko Tinbergen, Giard's ethology was not a discipline at all but, rather, a scientific attitude. This scientific attitude triggered a reappraisal of fieldwork, but at the same time Giard's ethology was never limited to the field alone. It also found its way to the laboratory, the museum, and the zoo. PMID- 20575489 TI - History without time: Buffon's natural history as a nonmathematical physique. AB - While "natural history" is practically synonymous with the name of Buffon, the term itself has been otherwise overlooked by historians of science. This essay attempts to address this omission by investigating the meanings of "physique," "natural philosophy," and "history," among other terms, with the purpose of understanding Buffon's actual objectives. It also shows that Buffon never claimed to be a Newtonian and should not be considered as such; the goal is to provide a historical analysis that resituates Buffon's thought within his own era. This is done, primarily, by eschewing the often-studied question of time in Buffon. Instead, this study examines the nontemporal meanings of the word "history" within the naturalist's theory and method. The title of his Natural History is examined both as an indicator of the kind of science that Buffon was hoping to achieve and as a source of great misinterpretation among his peers. Unlike Buffon, many of his contemporaries actually envisioned the study of nature from a Baconian perspective where history was restricted to the mere collection of facts and where philosophy, which was the implicit and ultimate goal of studying nature, was seen, at least for the present, as unrealizable. Buffon confronts this tendency insofar as his Histoire naturelle claims to be the real physique that, along with describing nature, also sought to identify general laws and provide clear insight into what true knowledge of nature is or should be. According to Buffon, history (both natural and civil) is not analogous to mathematics; it is a nonmathematical method whose scope encompasses both nature and society. This methodological stance gives rise to the "physicization" of certain moral concepts--a gesture that was interpreted by his contemporaries as Epicurean and atheist. In addition, Buffon reduces a number of metaphysically tainted historical concepts (e.g., antediluvian monuments) to objects of physical analysis, thereby confronting the very foundation of natural theology. In Buffon, as this essay makes clear, natural history is paving the way for a new physique (science of natural beings), independent from mathematics and from God, that treats naturalia in a philosophical and "historical" manner that is not necessarily "temporal." PMID- 20575491 TI - Focus: Global histories of science. Introduction. AB - An interest in global histories of science is not new. Yet the project envisioned by this Focus section is different from that pursued by natural historians and natural philosophers in the early modern age. Instead of tracing universal patterns, there is value in attending to the connections and disconnections of science on the global stage. Instead of assuming the precision of science's boundaries, historians might consider the categories of "science" and "indigenous knowledge" to have emerged from globalization. New global histories of science will be characterized by critical reflection on the limits of generalization, as well as a creative adoption of new sources, methods, and chronologies, in an attempt to decenter the European history of science. Such a project holds the promise of opening up new conversations between historians, anthropologists, philosophers, and sociologists of science. It is of critical importance if the discipline is not to fragment into regional and national subfields or become dominated by structural frameworks such as imperialism. PMID- 20575490 TI - A brave new animal for a brave new world: The British Laboratory Animals Bureau and the constitution of international standards of laboratory animal production and use, circa 1947-1968. AB - In 1947 the Medical Research Council of Britain established the Laboratory Animals Bureau in order to develop national standards of animal production that would enable commercial producers better to provide for the needs of laboratory animal users. Under the directorship of William Lane-Petter, the bureau expanded well beyond this remit, pioneering a new discipline of "laboratory animal science" and becoming internationally known as a producer of pathogenically and genetically standardized laboratory animals. The work of this organization, later renamed the Laboratory Animals Centre, and of Lane-Petter did much to systematize worldwide standards for laboratory animal production and provision--for example, by prompting the formation of the International Committee on Laboratory Animals. This essay reconstructs how the bureau became an internationally recognized center of expertise and argues that standardization discourses within science are inherently internationalizing. It traces the dynamic co-constitution of standard laboratory animals alongside that of the identities of the users, producers, and regulators of laboratory animals. This process is shown to have brought into being a transnational community with shared conceptual understandings and material practices grounded in the materiality of the laboratory animal, conceived as an instrumental technology. PMID- 20575492 TI - When science became Western: historiographical reflections. AB - While thinking about the notion of the "global" in the history of the history of science, this essay examines a related but equally basic concept: the idea of "Western science." Tracing its rise in the nineteenth century, it shows how it developed as much outside the Western world as within it. Ironically, while the idea itself was crucial for the disciplinary formation of the history of science, the global history behind this story has not been much attended to. Drawing on examples from nineteenth-century Egypt and China, the essay begins by looking at how international vectors of knowledge production (viz., missionaries and technocrats) created new global histories of science through the construction of novel genealogies and through a process of conceptual syncretism. Turning next to the work of early professional historians of science, it shows how Arabic and Chinese knowledge traditions were similarly reinterpreted in light of the modern sciences, now viewed as part of a diachronic and universalist teleology ending in "Western science." It concludes by arguing that examining the global emergence of the idea of Western science in this way highlights key questions pertaining to the relation of the history of science to knowledge traditions across the world and the continuing search for global histories of science. PMID- 20575493 TI - Global histories, vernacular science, and African genealogies; or, Is the history of science ready for the world? AB - Scholars in imperial and science studies have recently begun to examine more systematically the different ways knowledge systems around the world have intersected. This essay concentrates on one aspect of this process, the codification of research into "primitive" or "indigenous" knowledge, especially knowledge that was transmitted orally, and argues that such investigations were a by-product of four interrelated phenomena: the globalization of the sciences themselves, particularly those fields that took the earth and its inhabitants as their object of analysis; the professionalization of anthropology and its growing emphasis on studying other cultures' medical, technical, and natural knowledge; the European push, in the late nineteenth century, toward "global colonialism" and the ethnographic research that accompanied colonial state building; and, finally, colonized and marginalized peoples' challenges to scientific epistemologies and their paradoxical call that scientists study their knowledge systems more carefully. These phenomena came together on a global scale in the decades surrounding the turn of the twentieth century to produce a subgenre of research within the sciences, here labeled "vernacular science," focused explicitly on "native" knowledge. PMID- 20575494 TI - The enchantment of science in India. AB - In critiquing methodologies of the "global" as a spatial unit of analysis or a receptacle for influence across the planet, this essay positions India so as to assess the role and forms of science in the modern world. By taking the mid nineteenth century as a moment of departure, it asks why, under what conditions, and to what effects Indians accepted science, but not biomedicine, in the high noon of colonialism. Existing imperial histories of science that are primarily fixated on the eighteenth century cast science as a site of exchange and dialogue, thus replicating the narrative of European expansion overseas. Instead, the power of science is here understood in the context of the politics of religion and rationality. In a synoptic overview, the essay assesses the archaeology of science and the blurred practices between religion and science, described here as "insurgent." It argues that science in India was a form of enchantment, while religion had become a form of disenchanted but rational knowledge. Unlike in Europe, and contrary to orientalist positions, science in India neither declared the death of God nor became "spiritualized" via religion. Instead, science inflected religion; and religion, in turn, facilitated a rational mediation between science and man. This specific relationship accounts for the "soft landing" of science in India and its usurpation in the service of an unapologetic national modernity. PMID- 20575495 TI - Global knowledge on the move: itineraries, Amerindian narratives, and deep histories of science. AB - Since Bruno Latour's discussion of a Sakhalin island map used by La Perouse as part of a global network of "immutable mobiles," the commensurability of European and non-European knowledge has become an important issue for historians of science. But recent studies have challenged these dichotomous categories as reductive and inadequate for understanding the fluid nature of identities, their relational origins, and their historically constituted character. Itineraries of knowledge transfer, traced in the wake of objects and individuals, offer a powerful heuristic alternative, bypassing artificial epistemological divides and avoiding the limited scale of national or monolingual frames. Approaches that place undue emphasis either on the omnipotence of the imperial center or the centrality of the colonial periphery see only half the picture. Instead, practices of knowledge collection, codification, elaboration, and dissemination- in European, indigenous, and mixed or hybrid contexts--can be better understood by following their moveable parts, with a keen sensitivity toward non-normative epistemologies and more profound temporal frameworks. PMID- 20575496 TI - Sciences and the global: on methods, questions, and theory. AB - This essay explores the mechanics of researching and writing globally oriented histories of science. Thinking about how to approach sources is vital, especially given how often historians of science use the excuse of a lack of sources for constraining their projects to European topics. The first section suggests a method of cross-contextualization, where scarce and unorthodox sources are read within and alongside more plentiful and traditional ones. The next section considers historiography, critiquing the continuing hold of the terms "colonial" and "national" in current work that aspires to be more global. The final section considers practice and network theory, asking whether the way we utilize these tools in fact returns us, instinctively, to European and Eurocentric ways of conceiving how science works. PMID- 20575498 TI - Meaningful use of HIT saves lives. PMID- 20575499 TI - Meaningful users. Beyond EHRs: with kiosks, mobile access, and e-visits, this group practice is taking things to the next level of tech. PMID- 20575500 TI - How to find an attorney who's right for you--and your practice. Certain types of legal issues call for specific types of specialists. PMID- 20575501 TI - RAC program increases government scrutiny, risks. PMID- 20575502 TI - Another perspective on EHRs. Is typing during a patient exam akin to texting while driving? PMID- 20575503 TI - Extraordinarily high efficiency improvement for OLEDs with high surface-charge polymeric nanodots. AB - The efficiency of highly efficient blue, green, red, and white organic light emitting diodes (OLEDs) has been substantially advanced through the use of high surface-charge nanodots embedded in a nonemissive layer. For example, the blue OLED's markedly high initial power efficiency of 18.0 lm W(-1) at 100 cd m(-2) was doubled to 35.8 lm W(-1) when an amino-functionalized polymeric nanodot was employed. At high luminance, such as 1000 cd m(-2) used for illumination applications, the efficiency was improved from 12.4 to 21.2 lm W(-1), showing a significant enhancement of 71%. The incorporated highly charged nanodots are capable of effectively modulating the transportation of holes via a blocking or trapping mechanism, preventing excessive holes from entering the emissive layer and the resulting carrier-injection imbalance. Furthermore, in the presence of a high-repelling or dragging field arising from the highly charged nanodots, only those holes with sufficient energy are able to overcome the included barriers, causing them to penetrate deeper into the emissive layer. This penetration leads to carrier recombination over a wider region and results in a brighter emission and, therefore, higher efficiency. PMID- 20575504 TI - ZT enhancement in solution-grown Sb(2-x)BixTe3 nanoplatelets. AB - We report a solution-processed, ligand-supported synthesis of 15-20 nm thick Sb(2 x)BixTe3 nanoplatelets. After complete ligand removal by a facile NH3-based etching procedure, the platelets are spark plasma sintered to a p-type nanostructured bulk material with preserved crystal grain sizes. Due to this nanostructure, the total thermal conductivity is reduced by 60% in combination with a reduction in electric conductivity of as low as 20% as compared to the bulk material demonstrating the feasibility of the phonon-glass electron-crystal concept. An enhancement in the dimensionless thermoelectric figure of merit of up to 15% over state-of-the-art bulk materials is achieved, meanwhile, shifting the maximum to significantly higher temperatures. PMID- 20575506 TI - Oxygen-induced surface reconstruction of SrRuO3 and its effect on the BaTiO3 interface. AB - Atomically engineered oxide multilayers and superlattices display unique properties responsive to the electronic and atomic structures of the interfaces. We have followed the growth of ferroelectric BaTiO3 on SrRuO3 electrode with in situ atomic scale analysis of the surface structure at each stage. An oxygen induced surface reconstruction of SrRuO3 leads to formation of SrO rows spaced at twice the bulk periodicity. This reconstruction modifies the structure of the first BaTiO3 layers grown subsequently, including intermixing observed with cross section spectroscopy. These observations reveal that this common oxide interface is much more interesting than previously reported and provide a paradigm for oxygen engineering of oxide structure at an interface. PMID- 20575505 TI - Role of surface charge density in nanoparticle-templated assembly of bromovirus protein cages. AB - Self-assembling icosahedral protein cages have potentially useful physical and chemical characteristics for a variety of nanotechnology applications, ranging from therapeutic or diagnostic vectors to building blocks for hierarchical materials. For application-specific functional control of protein cage assemblies, a deeper understanding of the interaction between the protein cage and its payload is necessary. Protein-cage encapsulated nanoparticles, with their well-defined surface chemistry, allow for systematic control over key parameters of encapsulation such as the surface charge, hydrophobicity, and size. Independent control over these variables allows experimental testing of different assembly mechanism models. Previous studies done with Brome mosaic virus capsids and negatively charged gold nanoparticles indicated that the result of the self assembly process depends on the diameter of the particle. However, in these experiments, the surface-ligand density was maintained at saturation levels, while the total charge and the radius of curvature remained coupled variables, making the interpretation of the observed dependence on the core size difficult. The current work furnishes evidence of a critical surface charge density for assembly through an analysis aimed at decoupling the surface charge and the core size. PMID- 20575507 TI - Simple screening method for autoantigen proteins using the N-terminal biotinylated protein library produced by wheat cell-free synthesis. AB - Autoimmune diseases are a heterogeneous group of diseases characterized by immune reactions against either a major or a limited number of the bodies own autoantigens, causing inflammation and damage to tissues and organs. Thus, identification of autoantigens is an important first step to understanding autoimmune diseases. Here we demonstrate a simple screening method for identification of autoantigens reacting with patient serum antibodies by combination of an N-terminal biotinylated protein library (BPL), produced using a wheat cell-free protein production system, and a commercially available luminescence system. Optimization studies using well-characterized autoantigens showed specific interactions between N-terminal biotinylated proteins and antibody that were sensitively detected under homogeneous reaction conditions. In this optimized assay, 1 microL of the translation mixture expressing the biotinylated proteins produced significant luminescence signal by addition of diluted serum between 1:500 and 1:10 000 in 25 microL of reaction volume. For the BPL construction, 214 mouse genes, consisting of 103 well-known autoantigens and 111 genes in the mouse autoimmune susceptibility loci, and the sera of MRL/lpr mouse were used as an autoimmune model. By this screening method, 25 well-known autoantigens and 71 proteins in the loci were identified as autoantigen proteins specifically reacting with sera antibodies. Cross-referencing with the Gene Ontology Database, 26 and 38 of autoantigen proteins were predicted to have nuclear localization and identified as membrane and/or extracellular proteins. The immune reaction of six randomly selected proteins was confirmed by immunoprecipitation and/or immunoblot analyses. Interestingly, three autoantigen proteins were recognized by immunoprecipitation but not by immunoblot analysis. These results suggest that the BPL-based method could provide a simple system for screening of autoantigen proteins and would help with identification of autoantigen proteins reacting with antibodies that recognize folded proteins, rather than denatured or unfolded forms. PMID- 20575508 TI - Mechanism and branching ratios of hydroxy ethers + (*)OH gas phase reactions: relevance of h bond interactions. AB - A theoretical study on the mechanism and branching ratios of the gas phase reactions of hydroxyl radicals with a series of hydroxy ethers is presented. This is the first report on branching ratios for these reactions. The studied hydroxy ethers are: methoxy-methanol (MM), ethoxy-methanol (EM), 1-methoxy-ethanol (1ME), 2-methoxy-ethanol (2ME), and 2-ethoxy-ethanol (2EE). All the possible H abstraction channels have been modeled, involving the rupture of C-H and O-H bonds. The H abstractions from the alcohol group were found to be almost negligible for all the studied systems. The role of H bond interactions in the transition states (TS) is discussed, as well as the importance of the location of the reaction site with respect to the alcohol and the ether functional groups. TSs with seven-member ring-like structures were found to lead to stronger H bond interactions than TSs with six- and five-member ring-like structures, with the latter leading to the weakest interactions. Kinetic calculations have been performed within the 250-440 K temperature range. Rate coefficients for the reactions of (*)OH with MM, EM, and 1ME are reported here for the first time. Nonlinear Arrhenius plots were found for all the overall reactions. Negative activation energies at room temperature are proposed for the (*)OH reactions with EM, 2ME, and 2EE. The excellent agreement with the scarce experimental data available supports the reliability of the data reported here for the first time. PMID- 20575511 TI - New mu(4)-oxido-bridged copper benzoate quasi-tetrahedron and bis-mu(3)-hydroxido bridged copper azide and copper thiocyanate stepped cubanes: core conversion, structural diversity, and magnetic properties. AB - [Cu(2)(mu(4)-O)Cu(2)] and [Cu(2)(mu(3)-OH)(2)Cu(2)] geometrical arrangements are found in a new family of tetranuclear complexes: [Cu(4)(mu(4)-O)(mu-bip)(2)(mu O(2)CPh)(4)].0.5CH(2)Cl(2) (1.0.5CH(2)Cl(2)), [Cu(4)(mu(3)-OH)(2)(mu bip)(2)(N(3))(4)] (2), and [Cu(4)(mu(3)-OH)(2)(mu-bip)(2)(NCS)(4)(DMF)(2)] (3.2DMF) [Hbip = 2,6-bis(benzyliminomethyl)-4-methylphenol; DMF = dimethylformamide]. These complexes have been characterized by X-ray crystallography, and their magnetic properties have been studied. Complex 1 reacts with azide and thiocyanate anions, leading to 2 and 3 with a change of the [Cu(4)(mu(4)-O)] core into [Cu(4)(mu(3)-OH)(2)] units. These compounds are new examples of [Cu(4)] complexes where Cu(II) ions are connected by two types of water-derived ligands: oxide and hydroxide. Formation of these [Cu(4)] complexes can be controlled by changing the bridging ligands, which allows an effective tuning of the self-assembly. The study of the magnetic properties reveals that these complexes exhibit strong intramolecular antiferromagnetic interactions to yield a S(T) = 0 ground state. For the three complexes, the temperature dependence of the magnetic susceptibility was fitted using a model with two isolated S = 1/2 dimers based on the H = -2J{S(Cu,1).S(Cu,2)} spin Hamiltonian with J/k(B) = -289 K for 1; J/k(B) = -464 and -405 K for 2 and 3, respectively (where J is the exchange constant through the oxido-phenoxido or hydroxido phenoxido bridges, respectively). PMID- 20575510 TI - Purification of gold nanoplates grown directly on surfaces for enhanced localized surface plasmon resonance biosensing. AB - Here we describe the synthesis and purification of Au nanoplates grown directly on surfaces by a chemical seed-mediated growth method. The synthesis involves the attachment of 3-5 nm diameter Au nanoparticle (NP) seeds onto glass and Si/SiOx surfaces and their subsequent growth into larger Au nanostructures by the chemical reduction of AuCl4- with ascorbic acid in the presence of cetyltrimethylammonium bromide (CTAB). We used two different growth solutions. Growth solution 1 (GS1) led to a sample with 74% Au nanospheres and 26% Au nanoplates, while growth solution 2 (GS2), with lower CTAB and higher ascorbic acid concentration, led to 56% nanospheres and 44% nanoplates. The average wavelength of maximum extinction (lambdamax) of the localized surface plasmon resonance (LSPR) band of these samples was 549 and 627 nm, respectively. The use of adhesive tape or sonication enables the preferential removal of spherical Au nanostructures in both cases, leaving samples with >90% Au nanoplates. The average lambdamax increased to 672 nm (GS1) and 664 nm (GS2) for taped samples and 780 nm (GS1) and 720 nm (GS2) for sonicated samples, consistent with a higher purity of Au nanoplates on the surface. In all cases, the purified nanoplates vary in size and shape, including triangular, circular, or hexagonal structures, leading to broad spectra or the appearance of multiple peaks. We tuned the average lambdamax of the LSPR band of the Au nanoplate samples from 540 to 780 nm by varying the sonication time from 0 to 135 s. The change in lambdamax upon binding of anti-IgG to the edges of the purified nanoplates increases with an increasing number of anti-IgG on the edges, is 4-8 times larger compared to that of spherical nanoparticles, and is larger for samples purified by sonication compared to taping because the former has a larger initial lambdamax. A sample of Au nanoplates purified by taping and functionalized with anti-IgG at the edge sites displayed a shift in lambdamax as large as 45 nm for a 10 pg/mL solution of IgG (<1 pM). PMID- 20575512 TI - Isolation, characterization, and bioactivity of cyclotides from the Micronesian plant Psychotria leptothyrsa. AB - Cyclotides, the largest known family of head-to-tail cyclic peptides, have approximately 30 amino acid residues with a complex structure containing a circular peptide backbone and a cystine knot. They are found in plants from the Violaceae and Rubiaceae families and are speculated to function in plant protection. In addition to their insecticidal properties, cyclotides display cytotoxic, anti-HIV, antimicrobial, and inhibition of neurotensin binding activities. Although cyclotides are present in all violaceous species hitherto screened, their distribution and expression in Rubiaceae are not fully understood. In this study, we show that Psychotria leptothyrsa var. longicarpa (Rubiaceae) contains a suite of different cyclotides. The cyclotide fractions were isolated by RP-HPLC, and sequences of six new peptides, named psyles A-F, were determined by MS/MS sequencing. One of these, psyle C, is the first rubiaceous linear variant known. Psyles A, C, and E were analyzed in a fluorometric microculture assay to determine cytotoxicity toward the human lymphoma cell line U937-GTB. The IC(50) values of psyles A, C, and E were 26, 3.50, and 0.76 muM, respectively. This study expands the number of known rubiaceous cyclotides and shows that the linear cyclotide maintains cytotoxicity. PMID- 20575513 TI - Accurate spectroscopic calibration for noninvasive glucose monitoring by modeling the physiological glucose dynamics. AB - The physiological lag between blood and interstitial fluid (ISF) glucose is a major challenge for noninvasive glucose concentration measurements. This is a particular problem for spectroscopic techniques, which predominantly probe ISF glucose, creating inconsistencies in calibration, where blood glucose measurements are used as a reference. To overcome this problem, we present a dynamic concentration correction (DCC) scheme, based on the mass transfer of glucose between blood and ISF, to ensure consistency with the spectral measurements. The proposed formalism allows the transformation of glucose in the concentration domain, ensuring consistency with the acquired spectra in the calibration model. Taking Raman spectroscopy as a specific example, we demonstrate that the predicted glucose concentrations using the DCC-based calibration model closely match the measured glucose concentrations, while those generated with the conventional calibration methods show significantly larger deviations from the measured values. In addition, we provide an analytical formula for a previously unidentified source of limiting uncertainty arising in spectroscopic glucose monitoring from a lack of knowledge of glucose kinetics in prediction samples. A study with human volunteers undergoing glucose tolerance tests indicates that this lag uncertainty, which is comparable in magnitude to the uncertainty arising from noise and nonorthogonality in the spectral data set, can be reduced substantially by employing the DCC scheme in spectroscopic calibration. PMID- 20575514 TI - Exploring the effects of H-bonding in synthetic analogues of nickel superoxide dismutase (Ni-SOD): experimental and theoretical implications for protection of the Ni-SCys bond. AB - Nickel superoxide dismutase (Ni-SOD) is a recently discovered SOD obtained from soil microbes and cyanobacteria that shares no structural or spectroscopic similarities with other isoforms of SOD. The enzyme is found in both the Ni(II) (Ni-SOD(red)) and Ni(III) (Ni-SOD(ox)) oxidation states in "as isolated" preparations of the enzyme from two separate and independently crystallized Streptomyces strains. Ni-SOD contains an unusual and unprecedented biological coordination sphere comprised of Cys-S and peptido-N donors. To understand the role of these donors, we have previously synthesized the monomeric Ni(II)N(2)S(2) complexes, (Et(4)N)[Ni(nmp)(SC(6)H(4)-p-Cl)] (2) and (Et(4)N)[Ni(nmp)(S(t)Bu)] (3) as Ni-SOD(red) models arising from the S,S-bridged precursor molecule, [Ni(2)(nmp)(2)] (1) (where nmp(2-) = doubly deprotonated form of N-2 (mercaptoethyl)picolinamide). In addition to 2 and 3, we report here three new complexes, (Et(4)N)[Ni(nmp)(S-o-babt)] (4), (Et(4)N)[Ni(nmp)(S-meb)] (5), and K[Ni(nmp)(S-NAc)] (6) (where (-)S-o-babt = thiolate of o-benzoylaminobenzene thiol; (-)S-meb = thiolate of N-(2-mercaptoethyl)benzamide; and (-)S-NAc = thiolate of N-acetyl-L-cysteine methyl ester), that provide a unique comparison as to the structural and reactivity effects imparted by H-bonding in square planar asymmetrically coordinated Ni(II)N(2)S(2) complexes. X-ray structural analysis in combination with cyclic voltammetry (CV), spectroscopic measurements, density functional theory (DFT) calculations, and reactivity studies with O(2) and various ROS were employed to gain insight into the role that H-bonding plays in NiN(2)S(2) complexes related to Ni-SOD. The experimental results coupled with theoretical analysis demonstrate that H-bonding to coordinated thiolates stabilizes S-based molecular orbitals relative to those arising from Ni(II), allowing for enhanced Ni contribution to the highest occupied molecular orbital (HOMO), which is predominantly of S-Ni pi* character. These studies provide a unique perspective on the role played by electronically different thiolates regarding the intimately coupled interplay and delicate balance of Ni- versus S based reactivity in Ni-SOD model complexes. The reported results have offered new insight into the chemistry that H-bonding/thiolate protonation imparts upon the Ni-SOD active site during catalysis, in particular, as a protective mechanism against oxidative modification/degradation. PMID- 20575515 TI - Synthesis and immune response of non-native isomers of vascular endothelial growth factor. AB - Native proteins often lack immunogenicity and thus limit vaccine and mAb development. We described here a unique method to enhance the immunogenicity of native proteins. This is achieved by creating non-native isomers of disulfide proteins (X-isomers) using the method of disulfide scrambling. X-isomers have the potential to be developed as vaccines and effective immunogens, as they are capable of breaking the immune tolerance and eliciting antibodies that cross react with the native protein. In this report, we describe production of X isomers of vascular endothelial growth factor (X-VEGF). The aim is to develop X VEGF for cancer immunotherapy targeting reduction of VEGF. The production of mouse X-VEGF is achieved by expressing the short version of VEGF (1-110) commonly shared by all VEGF isoforms, with two Cys --> Ala mutations at Cys(51) and Cys(60) to generate R-VEGF(110) (R stands for fully reduced). R-VEGF(110) was then allowed to undergo oxidative folding in the absence of denaturant to form N VEGF(110) (N stands for native) or in the presence of denaturant to generate five fractions of X-VEGF(110) isomers. While N-VEGF(110) exhibits only marginal immunogenicity in mice, all five fractions of X-VEGF(110) isomers were shown to elicit high titers of antibodies that cross-react with N-VEGF(110). In sera of immunized mice, the amounts of anti-N-VEGF antibodies elicited by X-VEGF(110) isomers range from 54 to 186 mug/mL, which are compatible with or greater than the concentration required for effective therapy using anti-VEGF MAbs. The underlying mechanism of enhanced immunogenicity of X-VEGF(110) is investigated and elaborated. These data suggest that X-VEGF(110) isomers are potential compounds in developing active immunotherapy for treatment of VEGFR bearing tumors and the wet form of age-related macular degeneration. PMID- 20575516 TI - Probing the arenium-ion (protontransfer) versus the cation-radical (electron transfer) mechanism of Scholl reaction using DDQ as oxidant. AB - DDQ/H(+) system readily oxidizes a variety of electron donors with oxidation potential as high as approximately 1.7 V to the corresponding cation radicals. A re-examination of the controversial arenium-ion versus cation-radical mechanisms for Scholl reaction using DDQ/H(+) together with commonly utilized FeCl(3) as oxidants led us to demonstrate that the reaction proceeds largely via a cation radical mechanism. The critical experimental evidence in support of a cation radical pathway for the Scholl reaction includes the following: (i) There is no reaction in Scholl precursors in a mixture of dichloromethane and various acids (10% v/v). (ii) The necessity to use powerful oxidants such as ferric chloride (FeCl(3)) or DDQ/H(+) for Scholl reactions is inconsistent with the arenium-ion mechanism in light of the fact that aromatization of the dihydro intermediates (formed via arenium-ion mechanism) can be easily accomplished with rather weak oxidants such as iodine or air. (iii) Various Scholl precursors with oxidation potentials 1.7 V vs SCE do not react. (iv) Finally, the feasibility of the dicationic intermediate, formed by loss of two electrons, has been demonstrated by its generation from a tetraphenylene derivative using DDQ/H(+) as an oxidant. PMID- 20575518 TI - Isothermal target and signaling probe amplification method, based on a combination of an isothermal chain amplification technique and a fluorescence resonance energy transfer cycling probe technology. AB - An iTPA (isothermal target and signaling probe amplification) method for the quantitative detection of nucleic acids, based on a combination of novel ICA (isothermal chain amplification) and fluorescence resonance energy transfer cycling probe technology (FRET CPT), is described. In the new ICA method, which relies on the strand displacement activity of DNA polymerase and the RNA degrading activity of RNase H, two displacement events occur in the presence of four specially designed primers. This phenomenon leads to powerful amplification of target DNA. Since the amplification is initiated only after hybridization of the four primers, the ICA method leads to high specificity for the target sequence. As part of the new ICA method, iTPA is achieved by incorporating FRET CPT to generate multiple fluorescence signals from a single target molecule. Using the resulting dual target and signaling probe amplification system, even a single copy level of a target gene can be successfully detected and quantified under isothermal conditions. PMID- 20575519 TI - Bimodal polarons and hole transport in poly(3-hexylthiophene):fullerene blend films. AB - The bimolecular recombination dynamics in blend films of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) has been studied by transient absorption spectroscopy. On a microsecond time scale, two polaron bands were observed at 700 and 1000 nm and exhibited different bimolecular recombination dynamics. The 700-nm band decayed with a time-independent bimolecular recombination rate of 10(-12) cm(3) s(-1). The activation energy was as small as approximately 0.078 eV independently of the carrier density. On the other hand, the 1000-nm band decayed with a time-dependent bimolecular recombination rate, which varied from 10(-12) to 10(-13) cm(3) s(-1), depending on time or carrier density. The activation energy decreased exponentially from 0.178 to 0.097 eV with the increase in the carrier density. Therefore, we assigned the 700-nm band to freely mobile delocalized polarons in crystalline P3HT domains and the 1000-nm band to localized polarons trapped in relatively disordered P3HT domains. At a charge density of 10(17) cm(-3), which corresponds to 1 sun open-circuit condition, some localized polarons exhibited trap-free bimolecular recombination due to trap-filling. These findings suggest that not only delocalized polarons but also some localized polarons play a crucial role in the efficient hole transport in P3HT:PCBM solar cells. PMID- 20575521 TI - Development plus kinetic and mechanistic studies of a prototype supported nanoparticle heterogeneous catalyst formation system in contact with solution: Ir(1,5-COD)Cl/gamma-Al2O3 and its reduction by H2 to Ir(0)n/gamma-Al2O3. AB - An important question and hence goal in catalysis is how best to transfer the synthetic and mechanistic insights gained from the modern revolution in nanoparticle synthesis, characterization, and catalysis to prepare the next generation of improved, supported-nanoparticle heterogeneous catalysts. It is precisely this question and to-date somewhat elusive goal which are addressed by the present work. More specifically, the global hypothesis investigated herein is that the use of speciation-controlled, well-characterized, solid oxide supported organometallic precatalysts in contact with solution will lead to the next generation of better composition, size- and shape-controlled, as well as highly active and reproducible, supported-nanoparticle heterogeneous catalysts-ones that can also be understood kinetically and mechanistically. Developed herein are eight criteria defining a prototype system for supported-nanoparticle heterogeneous catalyst formation in contact with solution. The initial prototype system explored is the precatalyst, Ir(1,5-COD)Cl/gamma-Al(2)O(3) (characterized via ICP, CO adsorption, IR, and XAFS spectroscopies), and the well-defined product, Ir(0)(n)/gamma-Al(2)O(3) (characterized by reaction stoichiometry, TEM, and XAFS). The Ir(0)(n)/gamma-Al(2)O(3) system proved to be a highly active and long-lived catalyst in the simple test reaction of cyclohexene hydrogenation and in comparison to two literature Ir(0)(n)/Al(2)O(3) heterogeneous catalysts examined under identical conditions. High activity (2.2-4.8-fold higher than that of the literature Ir(0)(n)/Al(2)O(3) catalysts tested under the same conditions) and good lifetime (> or = 220,000 total turnovers of cyclohexene hydrogenation) are observed, in part by design since only acetone solvent, cyclohexene, and H(2) are possible ligands in the resultant "weakly ligated/labile-ligand" supported nanoclusters. Significantly, the Ir(1,5-COD)Cl/gamma-Al(2)O(3) + H(2) --> Ir(0)(n)/gamma-Al(2)O(3) heterogeneous catalyst formation kinetics were also successfully monitored using the cyclohexene hydrogenation reporter reaction method previously developed and applied to solution-nanoparticle formation. The observed sigmoidal supported-nanoparticle heterogeneous catalyst formation kinetics, starting from the Ir(1,5-COD)Cl/gamma-Al(2)O(3) precatalyst, are closely fit by the two-step mechanism of slow continuous nucleation (A --> B, rate constant k(1) = 1.5(1.1) x 10(-3) h(-1)) followed by fast autocatalytic surface growth (A + B --> 2B, rate constant k(2) = 1.6(2) x 10(4) h(-1) M(-1)), where A is the Ir(1,5-COD)Cl/gamma-Al(2)O(3) precatalyst and B is the resultant Ir(0)(n)/gamma-Al(2)O(3) catalyst. The kinetics are significant in establishing the ability to monitor the formation of supported-nanoparticle heterogeneous catalysts in contact with solution. They also suggest that the nine synthetic and mechanistic insights from the two-step mechanism of nanoparticle formation in solution should now apply also to the formation of supported-nanoparticle heterogeneous catalysts in contact with solution. The results open the door for new syntheses of supported-nanoparticle heterogeneous catalysts under nontraditional, mild, and flexible conditions where supported organometallics and other precursors are in contact with solution, so that additional variables such as the solvent choice, added ligands, solution temperature, and so on can be used to control the catalyst formation steps and, ideally, the resultant supported nanoparticle heterogeneous catalyst composition, size, and shape. PMID- 20575520 TI - High yield sample preconcentration using a highly ion-conductive charge-selective polymer. AB - The development and analysis of a microfluidic sample preconcentration system using a highly ion-conductive charge-selective polymer [poly-AMPS (2-acrylamido-2 methyl-1-propanesulfonic acid)] is reported. The preconcentration is based on the phenomenon of concentration polarization which develops at the boundaries of the poly-AMPS with buffer solutions. A negatively charged polymer, poly-AMPS, positioned between two microchannels efficiently extracts cations through its large cross section, resulting in efficient anion sample preconcentration. The present work includes the development of a robust polymer that is stable over a wide range of buffers with varying chemical compositions. The sample preconcentration effect remains linear to over 3 mM (0.15 pmol) and 500 microM (15 fmol) for fluorescein and TRITC-tagged albumin solutions, respectively. The system can potentially be used for concentrating proteins on microfluidic devices with subsequent analysis for proteomic applications. PMID- 20575522 TI - First ultraperformance liquid chromatography based strategy for profiling intact proteins in complex matrices: application to the evaluation of the performance of olive ( Olea europaea L.) stone proteins for cultivar fingerprinting. AB - There is a clear need for accelerating protein separations by HPLC. Different proposals have been developed including the use of perfusion and monolithic stationary phases. Nevertheless, these stationary phases, in some occasions, do not provide enough efficiency to resolve these large molecules when they are present in complex matrices. Although ultraperformance liquid chromatography (UPLC) columns have been successfully used for the efficient and rapid separation of small molecules, this is the first time these columns were proposed for the separation of intact proteins in a real complex matrix: the olive stone. Two different strategies were employed for the extraction of olive proteins: enzymatic assisted extraction and buffered extraction. Five different columns traditionally employed for the separation of proteins were used, and results were compared with those obtained when using different sub-2 microm particle columns. Separations obtained with sub-2 mum particle columns significantly improved the separations obtained with the other columns. This paper also demonstrates the applicability of protein profiles obtained from the olive stone for the discrimination among olive varieties. PMID- 20575523 TI - Effect of electrostatic interactions and dynamic disorder on the distance dependence of charge transfer in donor-bridge-acceptor systems. AB - Using a tight-binding model of charge transport in systems with static and dynamic disorder, we present a theoretical study of the positive charge transfer in molecular assemblies that involve a hole donor and an acceptor connected by fluorene and phenyl bridges. Two parameters that determine the rate of charge transfer within the proposed model are the charge transfer integral between neighboring units and the site energies. Fluctuations in the values of the charge transfer integral and the energy landscape for hole transport were calculated by taking into account variations of the dihedral angle between neighboring units and electrostatic interaction of positive charge moving along the bridge and the negative charge that remains on the hole donor. Analysis of the dynamics of hole transfer and the distribution of the positive charge during this process allows the conclusion that the rapid fall of the hole transfer rate coefficient observed in experiments with short bridges (three and four structural units for systems with fluorene and phenyl bridges, respectively) can be attributed to the electrostatic interaction. This interaction is responsible for the formation of the effective barrier between donor and acceptor with the height that increases as the number of structural bridge units remains less than 3 (fluorene bridge) or 4 (phenyl bridge). For longer bridges, however, the effective barrier changes only weakly and now the charge transport is mostly dominated by the fluctuation assisted incoherent hole migration along the bridge. The latter mechanism exhibits much weaker dependence of the rate coefficient on the bridge length in agreement with the available experimental results. PMID- 20575524 TI - Bronsted analysis of an enzyme-catalyzed pseudo-deglycosylation reaction: mechanism of desialylation in sialidases. AB - The Micromonospora viridifaciens Y370G inverting mutant sialidase has been found to possess beta-sialidase activity with various fluoro-substituted phenyl beta sialosides. A reagent panel of seven mono- and difluorophenyl beta-d-sialosides was synthesized, and these compounds were used, in conjunction with the parent phenyl beta-d-sialoside, to probe the mechanism of M. viridifaciens Y370G mutant sialidase-catalyzed hydrolyses. These hydrolysis reactions mimic the deglycosylation reaction step of the crucial tyrosinyl enzyme-bound intermediate that is formed during the corresponding wild-type sialidase reactions. The derived Bronsted parameter (beta(lg)) on k(cat)/K(m) is -0.46 +/- 0.02 for the four substrates that display significant activity, and these span a range of leaving group abilities (as judged by the pK(a) of their conjugate acids being between 7.09 and 9.87). The 4-fluoro, 2,3- and 2,5-difluorosubstrates display a diminished activity, whereas the 3,5-difluoro compound undergoes catalyzed hydrolysis exceedingly slowly. These observations, taken with solvent deuterium kinetic isotope effects (k(H(2))(O)/k(D(2))(O)) on the catalyzed hydrolysis of the 2-fluorophenyl substrate of 0.88 +/- 0.24 (k(cat)/K(m)) and 1.16 +/- 0.12 (k(cat)) and the poor inhibition shown by phenol (IC(50) > 1 mM), are consistent with glycosidic C-O cleavage being rate determining for both k(cat)/K(m) and k(cat) with little or no protonation of the departing aryloxide leaving group. The kinetic data reported herein are consistent with rate-limiting glycoside hydrolysis occurring via two distinct transition states that incorporates a nonproductive binding component for the tighter binding substrates. PMID- 20575525 TI - Organocatalytic enantioselective hydroxymethylation of oxindoles with paraformaldehyde as C1 unit. AB - A bifunctional thiourea-tertiary amine-catalyzed asymmetric hydroxymethylation of 3-substituted oxindoles using paraformaldehyde as the C1 unit was developed. A wide scope of oxindoles, bearing C3 sterically congested quaternary carbon centers, were smoothly obtained in good to excellent yields (up to 99%) and high enantioselectivities (up to 91% ee) under mild reaction conditions. A more significant feature of this approach employs cheap and readily available paraformaldehyde as a hydroxymethylation C1 unit, which is activated by chiral bifunctional thiourea organocatalysts. PMID- 20575526 TI - Enhanced stability of PEG-block-poly(N-hexyl stearate l-aspartamide) micelles in the presence of serum proteins. AB - Polyethylene glycol-phospholipid micelles form a major class of nanocarriers in pharmacy and medicine due to proven capability in drug solubilization, sustained drug release, and evidence for targeted drug delivery in vivo. In this report, we have prepared micelles composed of PEG-block-poly(N-hexyl stearate l-aspartamide) (PEG-b-PHSA), having nine stearic acid side chains, and have studied their stability in the presence of serum proteins by Forster resonance energy transfer (FRET) experiments. In the presence of serum albumin, alpha and beta globulins, or gamma globulins, there are minimal changes in FRET over two hours in vitro, indicating integrity of PEG-b-PHSA micelles. In contrast, 1,2-distearoyl-sn glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (PEG-DSPE) micelles lose FRET over two hours in vitro, especially in the presence of alpha and beta globulins, indicating the disruption of PEG-DSPE micelles and leakage of fluorescent probes. Owing to the aliphatic nature of DSPE and PHSA, both PEG-b PHSA and PEG-DSPE micelles efficiently solubilize amphotericin B (AmB), a poorly water-soluble antifungal agent used to combat systemic mycoses. However, only PEG b-PHSA micelles gradually liberate AmB in the presence of alpha and beta globulins, based on time-dependent changes in the self-aggregation state of AmB, monitored by UV/vis spectroscopy. PEG-b-PHSA micelles are remarkably stable in the presence of serum proteins and a more stable alternative for poorly water soluble drugs, which have been solubilized by PEG-DSPE micelles. PMID- 20575527 TI - Iodinated NanoClusters as an inhaled computed tomography contrast agent for lung visualization. AB - Improvements to contrast media formulations may be an effective way to increase the accuracy and effectiveness of thoracic computed tomography (CT) imaging in disease evaluation. To achieve contrast enhancement in the lungs, a relatively large localized concentration of contrast media must be delivered. Inhalation offers a noninvasive alternative to intrapleural injections for local lung delivery, but effective aerosolization may deter successful imaging strategies. Here, NanoCluster technology was applied to N1177, a diatrizoic acid derivative, to formulate low density nanoparticle agglomerates with aerodynamic diameters 50%, resolution of (13)C(2) and (34)S fine structure peaks was achieved with the peptide MMMMG (approximately 330,000 RP) on a 3 T system, and the limit of detection was significantly reduced. PMID- 20575530 TI - Heterogeneous reaction of NO(2) on fresh and coated soot surfaces. AB - The heterogeneous reaction of nitrogen dioxide (NO(2)) on fresh and coated soot surfaces has been investigated to assess its role in night-time formation of nitrous acid (HONO) in the atmosphere. Soot surfaces were prepared by incomplete combustion of propane and kerosene fuels under lean and rich flame conditions and then processed by heating to evaporate semivolatile species or by coating with pyrene, sulfuric acid, or glutaric acid. Uptake kinetics and HONO yield measurements were performed in a low-pressure fast-flow reactor coupled to a chemical ionization mass spectrometer (CIMS), using atmospheric-level NO(2) concentrations. The uptake coefficient and the HONO yield upon interaction of NO(2) with nascent soot depend on the type of fuel and combustion regime and are the highest for samples prepared using fuel rich flame. Heating the nascent soot samples before exposure to NO(2) removes the organic material from the soot backbone, leading to a significant increase in NO(2) uptake coefficient and HONO yield. Continuous exposure to NO(2) reduces the reactivity of soot because of irreversible deactivation of the surface sites. Our results support the oxidation reduction mechanism involving adsorptive and reactive centers on soot surface where NO(2) is converted to HONO and other products. Coating of the soot surface by different materials to simulate atmospheric aging has a strong impact on its reactivity toward NO(2) and the resulting HONO production. Coating of pyrene has little effect on either reaction rate or HONO yield. Sulfuric acid coating does not alter the uptake coefficient, but significantly reduces the amount of HONO formed. Coating of glutaric acid significantly increases NO(2) uptake coefficient and HONO yield. The results of our study indicate that the reactivity and HONO generating capacity of internally mixed soot aerosol will depend on the chemical composition of the coating material and hence will vary considerably in different polluted environments. PMID- 20575531 TI - Combined electrochemical surface plasmon resonance for angle spread imaging of multielement electrode arrays. AB - A surface plasmon resonance imaging system combined with a multielement electrode array is described. An optical system with shaping optics is used to direct a wedge of light onto a gold-coated sample. The reflected light is detected in the form of an angle-spread image of the surface, with one direction denoting a variable incident angle and the other showing a span of locations along one lateral direction of the sample surface. At the proper incident angle, the angle spread image shows the complete surface plasmon resonance curve over a span of locations on the surface. This imaging system is combined with a sample configuration consisting of a series of gold microelectrode bands, each with independent electrochemical control. In solution, this system can be used to perform high-throughput and dynamic electrochemical experiments. Simultaneous measurement of electrochemical and surface plasmon resonance can be quantitatively performed on each of the electrode surfaces either by holding each electrode at a different potential value or by scanning the applied potential. The sensitivity of this configuration is demonstrated by monitoring oxide formation and removal at a gold electrode in an aqueous electrolyte. A second example, with the use of a thin poly(aniline) coating, illustrates the ability to monitor film changes, including thickness, dielectric properties, and associated electrochemically induced polymer oxidation/reduction on multiple electrodes. This represents a simple and compact method for combining the sensitivity of surface plasmon resonance into an array-based, high-throughput electrochemical system. PMID- 20575533 TI - Rational approaches toward the design and synthesis of zeolitic inorganic open framework materials. AB - Since the first synthesis of zeolites in 1940s, these materials and related inorganic open-framework materials with regular nanoporous space have attracted considerable interest. Zeolites are important for catalysis, adsorption, and ion exchange, and researchers are finding new applications for these materials in optics, electronics, sensors, and medicine. In particular, the petrochemical industry is interested in the synthesis of new zeolite catalysts with high catalytic activity and selectivity. Using hydrothermal, solvothermal, and the recently-developed ionothermal methods, researchers have prepared 194 types of zeolites and thousands of zeolite-related inorganic open-framework materials. However, their syntheses are based primarily on an empirical "trial-and-error" method. The rational synthesis of zeolitic inorganic open-framework materials, while targeting novel structures and functions, remains a formidable task. The challenge in rational synthesis lies in the unknown mechanism for their formation: the relationship between the synthetic parameters and structural characteristics of the products is not clear. In an effort to overcome these challenges, our group has built up a ZEOBANK, a database of zeolite structures and a database for their synthesis. ZEOBANK allows us to use data mining to find new methods for guiding the synthesis of zeolitic materials. In this Account, we describe our efforts to rationally synthesize zeolitic inorganic open-framework materials with desired structures and present computational methods for the design of these structures. In particular, we focus on the design of zeolites with desired pore geometries through constrained assembly of atoms around the predefined channels in the unit cell. Our approaches toward rational synthesis include the use of template to direct the structure, the use of heteroatoms as a framework substituent, and the use of computational data mining. Employing these strategies, we have developed innovative methods toward the synthesis of target structures with specific channel structures, such as extra-large pores and chiral channels. We expect that further data mining will increase the synthetic control for researchers interested in designing functional zeolitic materials. PMID- 20575532 TI - Functional and structural impact of target uridine substitutions on the H/ACA ribonucleoprotein particle pseudouridine synthase. AB - Box H/ACA ribonucleoprotein protein particles catalyze the majority of pseudouridylation in functional RNA. Different from stand alone pseudouridine synthases, the RNP pseudouridine synthase comprises multiple protein subunits and an RNA subunit. Previous studies showed that each subunit, regardless its location, is sensitive to the step of subunit placement at the catalytic center and potentially to the reaction status of the substrate. Here we describe the impact of chemical substitutions of target uridine on enzyme activity and structure. We found that 3-methyluridine in place of uridine inhibited its isomerization while 2'-deoxyuridine or 4-thiouridine did not. Significantly, crystal structures of an archaeal box H/ACA RNP bound with the nonreactive and the two postreactive substrate analogues showed only subtle structural changes throughout the assembly except for a conserved tyrosine and a substrate anchoring loop of Cbf5. Our results suggest a potential role of these elements and the subunit that contacts them in substrate binding and product release. PMID- 20575535 TI - Real time in situ detection of organic nitrates in atmospheric aerosols. AB - A novel instrument is described that quantifies total particle-phase organic nitrates in real time with a detection limit of 0.11 microg m(-3) min(-1), 45 ppt min(-1) (-ONO(2)). Aerosol nitrates are separated from gas-phase nitrates with a short residence time activated carbon denuder. Detection of organic molecules containing -ONO(2) subunits is accomplished using thermal dissociation coupled to laser induced fluorescence detection of NO(2). This instrument is capable of high time resolution (seconds) measurements of particle-phase organic nitrates, without interference from inorganic nitrate. Here we use it to quantify organic nitrates in secondary organic aerosol generated from high-NO(x) photooxidation of limonene, alpha-pinene, Delta-3-carene, and tridecane. In these experiments the organic nitrate moiety is observed to be 6-15% of the total SOA mass. PMID- 20575536 TI - Trophodynamics of hexabromocyclododecanes and several other non-PBDE brominated flame retardants in a freshwater food web. AB - Several currently used non-polybrominated diphenyl ether (PBDE) brominated flame retardants (BFRs), including hexabromocyclododecanes (HBCDs), 1,2-bis(2,4,6 tribromophenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), hexabromobenzene (HBB), pentabromoethylbenzene (PBEB), and pentabromotoluene (PBT), are examined in the components of a freshwater food web from an electronic waste recycling site, South China. All these BFRs are detectable in the food web, with average concentrations of 13.9-868, 1.71-518, < 3.8-338, 197-3099, 3.98 25.6, and 1.20-3.60 ng/g lipid wt for HBCDs, BTBPE, DBDPE, HBB, PBEB, and PBT, respectively. Food web magnification is observed for (+)-alpha-, (-)-alpha-, (+/ )-alpha-, and total HBCDs, and HBB, with trophic magnification factors (TMFs) of 2.22, 2.18, 2.19, 1.82, and 1.46, respectively; whereas there is trophic dilution of BTBPE and PBT through the food web. The TMFs for (+)-alpha-, (-)-alpha-, and (+/-)-alpha-HBCDs are comparable to those of PBDEs detected previously in the same food web. Biota samples show a shift from gamma- toward alpha-HBCD compared with the suspended particles, sediment, and HBCD technical mixtures, with a significant increase of alpha-HBCD on ascending trophic levels. Except for alpha HBCD in suspended particles and sediment, all the HBCD enantiomers detected are nonracemic in the environmental matrix. In biota, nonracemic residues of alpha HBCD were observed in mud carp and crucian carp; beta-HBCD in prawn, mud carp, and crucian carp; and gamma-HBCD in water snake, with preferences for (+)-alpha-, (-)-beta-, and (+)-gamma-HBCDs. PMID- 20575534 TI - Characterization of membrane protein non-native states. 1. Extent of unfolding and aggregation of rhodopsin in the presence of chemical denaturants. AB - Little is known about the general folding mechanisms of helical membrane proteins. Unfolded, i.e., non-native states, in particular, have not yet been characterized in detail. Here, we establish conditions under which denatured states of the mammalian membrane protein rhodopsin, a prototypic G protein coupled receptor with primary function in vision, can be studied. We investigated the effects of the chemical denaturants sodium dodecyl sulfate (SDS), urea, guanidine hydrochloride (GuHCl), and trifluoroacetic acid (TFA) on rhodopsin's secondary structure and propensity for aggregation. Ellipticity at 222 nm decreases in the presence of maximum concentrations of denaturants in the order TFA > GuHCl > urea > SDS + urea > SDS. Interpretation of these changes in ellipticity in terms of helix loss is challenged because the addition of some denaturants leads to aggregation. Through a combination of SDS-PAGE, dependence of ellipticity on protein concentration, and 1D (1)H NMR we show that aggregates form in the presence of GuHCl, TFA, and urea but not in any concentration of SDS, added over a range of 0.05%-30%. Mixed denaturant conditions consisting of 3% SDS and 8 M urea, added in this order, also did not result in aggregation. We conclude that SDS is able to prevent the exposure of large hydrophobic regions present in membrane proteins which otherwise leads to aggregation. Thus, 30% SDS and 3% SDS + 8 M urea are the denaturing conditions of choice to study maximally unfolded rhodopsin without aggregation. PMID- 20575537 TI - Toxicological relevance of pharmaceuticals in drinking water. AB - Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected. PMID- 20575538 TI - In situ identification of intermediates of benzyl chloride reduction at a silver electrode by SERS coupled with DFT calculations. AB - Aiming to deeply understand the electrocatalytic mechanism of silver on reduction of benzyl chloride, we carried out an in situ electrochemical surface-enhanced Raman spectroscopic study to characterize various surface species in different electrode potential regions. A further analysis with DFT calculation reveals that the benzyl radical and its anionic derivate bonded on a silver electrode are the key intermediates, implying that the pathway could drastically differ from the outer sphere concerted electron reduction at inert electrodes. PMID- 20575539 TI - Fullerene-like colloidal nanocrystal of nickel hydroxychloride. AB - In this work, we successfully fabricated near-monodisperse colloids of a new type of inorganic fullerene-like structure (IF) of nickel hydroxychloride as the first example of the application of colloidal synthetic routes to the synthesis of IFs. The formation mechanism and interesting magnetic properties are briefly discussed. PMID- 20575540 TI - Production of volatile metabolites by grape-associated microorganisms. AB - Plant-associated microorganisms fulfill important functions for their hosts. Whereas promotion of plant growth and health is well-studied, little is known about the impact of microorganisms on plant or fruit flavor. To analyze the production of volatiles of grape-associated microorganisms, samples of grapes of the red cultivar 'Blaufraenkisch' were taken during harvest time from four different vineyards in Burgenland (Austria). The production of volatiles was analyzed for the total culturable microbial communities (bacteria, yeasts, fungi) found on and in the grapes as well as for single isolates. The microbial communities produced clearly distinct aroma profiles for each vineyard and phylogenetic group. Furthermore, half of the grape-associated microorganisms produced a broad spectrum of volatile organic compounds. Exemplary, the spectrum was analyzed more in detail for three single isolates of Paenibacillus sp., Sporobolomyces roseus , and Aureobasidium pullulans . Well-known and typical flavor components of red wine were detected as being produced by microbes, for example, 2-methylbutanoic acid, 3-methyl-1-butanol, and ethyl octanoate. PMID- 20575542 TI - Interfacially controlled synthesis of hollow mesoporous silica spheres with radially oriented pore structures. AB - This paper reports an alternative process to prepare hollow mesoporous silica spheres (HMS) using a single cationic surfactant with a tunable wall thickness and radially oriented pore structures. Using N,N-dimethylformide (DMF) as the intermediate solvent bridging the organic and aqueous phase, hollow mesoporous silica spheres were synthesized with interfacial hydrolysis reactions at the surface of liquid droplets. These spheres have an ordered pore structure aligned along the radial direction, and the wall thickness and sphere sizes can be tuned by adjusting the experimental conditions. Transmission electron microscopy and nitrogen absorption techniques were used to characterize HMS and its formation procedure. A hypothetic formation mechanism was proposed on the basis of a morphology transformation with the correct amount of DMF and a careful observation of the early hydrolysis stages. Au and magnetic Fe(3)O(4) nanoparticles have been encapsulated in the HMS hollow core for potential applications. PMID- 20575541 TI - Thymidylate synthase catalyzed H-transfers: two chapters in one tale. AB - Examination of the nature of different bond activations along the same catalytic path is of general interest in chemistry and biology. In this report, we compare the physical nature of two sequential H-transfers in the same enzymatic reaction. Thymidylate synthase (TSase) catalyzes a complex reaction that involves many chemical transformations including two different C-H bond cleavages, a rate limiting C-H-C hydride transfer and a non-rate-limiting C-H-O proton transfer. Although the large kinetic complexity imposes difficulties in studying the proton transfer catalyzed by TSase, we are able to experimentally extract the intrinsic kinetic isotope effects (KIEs) on both steps. In contrast with the hydride transfer, the intrinsic KIEs of the proton transfer are temperature dependent. The results are interpreted within the framework of the Marcus-like model. This interpretation suggests that TSase optimizes the donor-acceptor geometries for the slower and overall rate-limiting hydride transfer but not for the faster proton transfer. PMID- 20575543 TI - Kinetics of fibrinogen adsorption on hydrophilic substrates. AB - Irreversible side-on adsorption of fibrinogen, modeled as a linear chain of touching beads of various size, was studied theoretically using the random sequential adsorption (RSA) model. Numerical simulation of the Monte Carlo type enabled one to determine the dependence of the surface blocking function (available surface function) on the protein coverage. These numerical results were interpolated using analytical functions based on a polynomial expansion. The dependence of the jamming coverage on the size of the simulation area was also determined. By an extrapolation of these results to the infinite area size, the maximum surface concentration of fibrinogen for the side-on adsorption was determined to be 2.26 x 10(3) microm(-2). This corresponds to a jamming coverage theta(infinity) of 0.29. It was shown that the blocking function can well be approximated in the limit of high coverage by the dependence C(theta(infinity) - theta)(4). Using this interpolating expression, the kinetics of fibrinogen adsorption under convection and diffusion transport conditions were evaluated for various bulk concentrations of the protein. These kinetic curves were derived by numerically solving the mass transport equation in the bulk with the blocking function used as a nonlinear boundary condition at the interface. It was shown that our theoretical results are in agreement with experimental kinetic data obtained by AFM, ellipsometry, and other techniques for hydrophilic surfaces in the limit of low bulk fibrinogen concentration. PMID- 20575544 TI - Effect of matrix molecular weight on the coarsening mechanism of polymer-grafted gold nanocrystals. AB - A systematic evaluation of the effect of polymer matrix molecular weight on the coarsening kinetics of uniformly dispersed polystyrene-grafted gold nanoparticles is presented. Particle coarsening is found to proceed via three stages (i.e., atomic-diffusion-based Ostwald ripening (OR), particle-migration-based collision coalescence, and the subsequent reshaping of particle assemblies). The relative significance of each stage and hence the evolution of particle size and shape have been found to depend sensitively upon time, temperature, and the molecular weight of the host polymer. At temperatures close to the matrix glass-transition temperature, Ostwald ripening has been observed to be dominant on all experimental timescales. With increasing annealing temperature, collision coalescence becomes the dominant mode of coarsening, leading to rapid particle growth. The onset of the latter process is found to be increasingly delayed with increasing molecular weight of the polymer host. Particle coalescence is observed to proceed via two fundamental modes (i.e., diffusion-limited aggregation and growth resulting in the formation of fractal particle clusters and the subsequent recrystallization into more spherical monolithic aggregate structures). Interestingly, particle coarsening in high-molecular-weight matrix polymers is found to proceed significantly faster than predicted on the basis of the bulk polymer viscosity; this acceleration is interpreted to be a consequence of the network characteristics of high-molecular-weight polymers by analogy to the phenomenon of nanoviscosity that has been reported in the context of nanoparticle diffusion within high-molecular-weight polymers. PMID- 20575545 TI - Effect of O2, CO, and NO on surface segregation in a Rh0.5Pd0.5 bulk crystal and comparison to Rh0.5Pd0.5 nanoparticles. AB - We present an in situ study of the interaction of a bimetallic Rh(0.5)Pd(0.5) bulk crystal with O(2), CO, and NO using ambient pressure X-ray photoelectron spectroscopy (APXPS) and compare it to results for 15 nm nanoparticles with the same overall composition. The bulk crystal surface has less Rh present under both oxidizing and reducing conditions than the surface of nanoparticles under identical conditions. Segregation and oxidation/reduction proceeds faster and at lower temperature for nanoparticles than for the bulk crystal. The near surface of the Rh(0.5)Pd(0.5) bulk crystal after high temperature vacuum annealing is ca. 9% Rh measured by APXPS. Heating in 0.1 Torr O(2) to 350 degrees C increases the Rh surface composition to ca. 40%. The surface can then be reduced by heating in H(2) at 150 degrees C, leading to a chemically reduced surface with 30% Rh. Titration of CO by gas-phase O(2) from this Rh-rich surface proceeds at a much lower pressure than that on the Rh-deficient starting surface. PMID- 20575546 TI - Controlling gold nanoparticle stability with triggerable microgels. AB - The interaction of a photodegradable surfactant (PS, 4-hexylphenylazosulfonate, C(6)PAS) with microgels (MGs) of poly(2-vinyl pyridine) (MGA) in the protonated state (pH 3) has been investigated. Electrophoretic mobility measurements confirm that negatively charged PS interacts with positively charged MGA to form mixed PS MG complexes. This was sensed by a decrease in the effective PS-MGA charge and a switch in sign of electrophoretic mobility, from positive to negative, with increasing PS concentration. After the addition of extra positive microgels (MGB), the system undergoes coflocculation. Incident UV irradiation was used to photolyze the anionic PS, effectively eliminating the headgroups, thereby lowering the electrostatic interactions between PS and MGA microgel networks. Consequently, a reversal of MGA charge occurred, leading to electrostatic repulsions and causing the MGs to reswell and redisperse, with both MGA and MGB now being positively charged and hence stabilized against coflocculation. Extending this approach, negatively charged gold nanoparticles (AuMES) have been incorporated into the PS-MGA complexes. Atomic absorption spectroscopy (AAS) showed that 100% of the AuMES particles were recovered after coflocculation of (PS-MGA)-AuMES complexes with MGB. Furthermore, approximately 75% of the AuMES could be redispersed after UV irradiation to restabilize the dispersion. This system provides an interesting method for phase separation and gold nanoparticle recovery for reuse and recycling. PMID- 20575547 TI - Novel carboxyl-amine bonding methods for poly(dimethylsiloxane)-based devices. AB - We present a novel bonding technique for poly(dimethylsiloxane) (PDMS)-based devices employing chemical surface modifications at room temperature. PDMS surfaces were functionalized to present primary amine groups, and glass or gold substrates were functionalized to present carboxylic acid groups. Irreversible bonding was achieved by bringing the two surfaces in contact and reacting at room temperature to form peptide bonds between the substrates. Shear tests reveal the bond strengths achieved to be comparable to values obtained using conventional bonding methods. We also describe the use of carboxyl-terminated silanes on gold surfaces to bond amine-modified PDMS devices. Water contact angle measurements and X-ray photoelectron spectroscopy (XPS) confirmed the conjugation, a novel result that expands the variety of surface chemistries available for such bonding. PMID- 20575548 TI - Dead-end filling of SlipChip evaluated theoretically and experimentally as a function of the surface chemistry and the gap size between the plates for lubricated and dry SlipChips. AB - In this paper, we describe a method to load a microfluidic device, the SlipChip, via dead-end filling. In dead-end filling, the lubricating fluid that fills the SlipChip after assembly is dissipated through the gap between the two plates of the SlipChip instead of flowing through an outlet at the end of the fluidic path. We describe a theoretical model and associated predictions of dead-end filling that takes into consideration the interfacial properties and the gap size between plates of SlipChips. In this method, filling is controlled by the balance of pressures: for filling to occur without leaking, the inlet pressure must be greater than the capillary pressure but less than the maximum sealing pressure. We evaluated our prediction with experiments, and our empirical results agreed well with theory. Internal reservoirs were designed to prevent evaporation during loading of multiple solutions. Solutions were first loaded one at a time into inlet reservoirs; by applying a single pressure source to the device, we were able to fill multiple fluidic paths simultaneously. We used this method to fill both lubricated and dry SlipChips. Dry-loaded SlipChips were fabricated from fluorinated ethylene propylene (FEP) by using hot embossing techniques, and were successfully filled and slipped to perform a simple chemical reaction. The SlipChip design was also modified to enable ease of filling by using multiple access holes to the inlet reservoir. PMID- 20575549 TI - Mean square displacements from elastic incoherent neutron scattering evaluated by spectrometers working with different energy resolution on dry and hydrated (H2O and D2O) lysozyme. AB - The main aim of the present paper is the evaluation of the effects of the instrumental energy resolution on the mean square displacement (MSD) obtained by elastic incoherent neutron scattering (EINS). In particular, this study is performed in the time domain, through the time-Fourier transform of the elastically scattered neutron intensity, and is mainly focused on the connection between the system MSD and the measured MSD. It is shown how in the case of EINS, the instrumental energy resolution gives rise to the time integration of the time dependent system MSD function weighted in time by the resolution function. The formulated approach is applied to the data collected on dry and hydrated (H(2)O and D(2)O with h = 0.4) lysozyme samples by two spectrometers working with a different instrumental resolution (the IN10 and IN13 spectrometers of the Institute Laue-Langevin). As a result, the procedure furnishes an excellent agreement for the system MSD evaluated in the low temperature range up to T = 40 K. PMID- 20575550 TI - Analysis of the binding of mixed lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the design of inhibitors of the MLL1-WDR5 interaction. AB - MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methyltransferase activity of MLL1 and targeting this interaction using small molecules may represent an attractive therapeutic strategy. In this study, we have defined the essential elements in MLL1 required for its high-affinity binding to WDR5. Our data showed that the minimal elements crucial for high affinity binding of MLL1 to WDR5 are -CO-ARA-NH- motif and two intramolecular hydrogen bonds that stabilize the conformation of this motif. Two 3-mer peptides, Ac-ARA-NH(2) and Ac-ART-NH(2), were designed based upon MLL1 and H3 sequences and achieved K(i) values of 120 and 20 nM to WDR5, respectively. Our study provides a concrete basis for the design of potent peptidomimetics and nonpeptidic compounds to inhibit MLL1 activity by targeting the MLL1 and WDR5 interaction. PMID- 20575551 TI - Copolymerization behavior of N-(2-hydroxypropyl)methacrylamide and a methacrylated coiled-coil peptide derivative. PMID- 20575552 TI - Thermally responsive injectable hydrogel incorporating methacrylate-polylactide for hydrolytic lability. AB - Injectable thermoresponsive hydrogels are of interest for a variety of biomedical applications, including regional tissue mechanical support as well as drug and cell delivery. Within this class of materials there is a need to provide options for gels with stronger mechanical properties as well as variable degradation profiles. To address this need, the hydrolytically labile monomer, methacrylate polylactide (MAPLA), with an average 2.8 lactic acid units, was synthesized and copolymerized with N-isopropylacrylamide (NIPAAm) and 2-hydroxyethyl methacrylate (HEMA) to obtain bioabsorbable thermally responsive hydrogels. Poly(NIPAAm-co HEMA-co-MAPLA) with three monomer feed ratios (84/10/6, 82/10/8, and 80/10/10) was synthesized and characterized with NMR, FTIR, and GPC. The copolymers were soluble in saline at reduced temperature (<10 degrees C), forming clear solutions that increased in viscosity with the MAPLA feed ratio. The copolymers underwent sol-gel transition at lower critical solution temperatures of 12.4, 14.0, and 16.2 degrees C, respectively, and solidified immediately upon being placed in a 37 degrees C water bath. The warmed hydrogels gradually excluded water to reach final water contents of approximately 45%. The hydrogels as formed were mechanically strong, with tensile strengths as high as 100 kPa and shear moduli of 60 kPa. All three hydrogels were completely degraded (solubilized) in PBS over a 6-7 month period at 37 degrees C, with a higher MAPLA feed ratio resulting in a faster degradation period. Culture of primary vascular smooth muscle cells with degradation solutions demonstrated a lack of cytotoxicity. The synthesized hydrogels provide new options for biomaterial injection therapy where increased mechanical strength and relatively slow resorption rates would be attractive. PMID- 20575553 TI - The pthaladyns: GTP competitive inhibitors of dynamin I and II GTPase derived from virtual screening. AB - We report the development of a homology model for the GTP binding domain of human dynamin I based on the corresponding crystal structure of Dictyostelium discoidum dynamin A. Virtual screening identified 2-[(2-biphenyl-2-yl-1,3-dioxo-2,3-dihydro 1H-isoindole-5-carbonyl)amino]-4-chlorobenzoic acid (1) as a approximately 170 microM potent inhibitor. Homology modeling- and focused library-led synthesis resulted in development of a series of active compounds (the "pthaladyns") with 4 chloro-2-(2-(4-(hydroxymethyl)phenyl)-1,3-dioxoisoindoline-5-carboxamido)benzoic acid (29), a 4.58 +/- 0.06 microM dynamin I GTPase inhibitor. Pthaladyn-29 displays borderline selectivity for dynamin I relative to dynamin II ( approximately 5-10 fold). Only pthaladyn-23 (dynamin I IC(50) 17.4 +/- 5.8 microM) was an effective inhibitor of dynamin I mediated synaptic vesicle endocytosis in brain synaptosomes with an IC(50) of 12.9 +/- 5.9 microM. This compound was also competitive with respect to Mg(2+).GTP. Thus the pthaladyns are the first GTP competitive inhibitors of dynamin I and II GTPase and may be effective new tools for the study of neuronal endocytosis. PMID- 20575554 TI - Ligand specificity in fragment-based drug design. AB - Fragment-based drug design consists of identifying low-molecular weight compounds that weakly bind to a target macromolecule and will then be modified or linked to yield potent inhibitors. The specificity of these low-complexity and low-affinity molecules has rarely been discussed in the literature. To address this question, NMR spectroscopy was used to investigate the interactions of 150 fragments with five proteins: three proteins from the Bcl-2 family (Bcl-x(L), Bcl-w, and Mcl-1), human peroxiredoxin 5, for which very few ligands have been reported, and human serum albumin, which is known to bind a large number of ligands. Our results show that the fragments are rather versatile binders and able to identify binding hot spots in very different targets. Despite the different hit rates observed related to the druggability of the proteins, two scaffolds appear as preferred binders for all proteins. Low specificity was observed between homologous proteins or unrelated poorly druggable proteins, while higher specificity could be achieved with highly druggable targets. PMID- 20575556 TI - Modulation of the excited state intramolecular electron transfer reaction and dual fluorescence of crystal violet lactone in room temperature ionic liquids. AB - The influence of polarity, viscosity, and hydrogen bond donating ability of the medium on the fluorescence behavior of crystal violet lactone (CVL), which undergoes excited state electron transfer reaction and exhibits dual fluorescence from two different electronic states, termed as CT(A) and CT(B), has been studied in six different room temperature ionic liquids (ILs) using steady state and time resolved emission techniques. It is shown that the excited state CT(A) --> CT(B) transformation and dual fluorescence of CVL can be controlled by appropriate choice of the ILs. While dual fluorescence of CVL is clearly observed in pyrrolidinium IL, the molecule exhibits a single fluorescence band in ammonium IL. While the second emission from the CT(B) state can barely be seen in 1,3 dialkylimidazolium ILs, dual fluorescence is quite prominent in 1-butyl-2,3 dimethylimidazolium IL, [bmMim][Tf(2)N]. These contrasting results have been explained taking into account the hydrogen bonding interactions of the 1,3 dialkylimidazolium ions (mediated through the C(2)-hydrogen) with CVL and the viscosity of the ILs. The excited state CT(A) --> CT(B) reaction kinetics has been studied in IL by monitoring the time-evolution of the CT(B) emission in [bmMim][Tf(2)N]. The solvation dynamics in this IL has been studied by following the dynamic fluorescence Stokes shift of C153, which is used as a probe molecule. A comparison of the excited state reaction time and solvation time suggests that the rate of the CT(A) --> CT(B) reaction in moderately viscous ILs is primarily dictated by the rate of solvation. Very little or negligible excitation wavelength dependence of the emission behavior of CVL can be observed in these ILs. PMID- 20575555 TI - Synthesis, inhibitory activity of cholinesterases, and neuroprotective profile of novel 1,8-naphthyridine derivatives. AB - 1,8-Naphthyridine derivatives related to 17 (ITH4012), a neuroprotective compound reported by our research group, have been synthesized. In general, they have shown better inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) than most tacrine derivatives previously synthesized in our laboratory. The compounds presented an interesting neuroprotective profile in SH-SY5Y neuroblastoma cells stressed with rotenone/oligomycin A. Moreover, compound 14 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3 carboxylate) also caused protection in cells stressed with okadaic acid (OA) or amyloid beta 1-42 peptide (Abeta(1-42)). Interestingly, compound 14 prevented the OA-induced PP2A inhibition, one of the enzymes implicated in tau dephosphorylation. This compound also exhibited neuroprotection against neurotoxicity elicited by oxygen and glucose deprivation in hippocampal slices. Because these stressors caused neuronal damage related to physiopathological hallmarks found in the brain of Alzheimer's disease (AD) patients, we conclude that compound 14 deserves further in vivo studies in AD models to test its therapeutic potential in this disease. PMID- 20575560 TI - Three-dimensional atom probe tomography of oxide, anion, and alkanethiolate coatings on gold. AB - We have used three-dimensional atom probe tomography to analyze several nanometer thick and monomolecular films on gold surfaces. High-purity gold wire was etched by electropolishing to create a sharp tip suitable for field evaporation with a radius of curvature of <100 nm. The near-surface region of a freshly etched gold tip was examined with the atom probe at subnanometer spatial resolution and with atom-level composition accuracy. A thin contaminant layer, primarily consisting of water and atmospheric gases, was observed on a fresh tip. This sample exhibited crystalline lattice spacings consistent with the interlayer spacing of {200} lattice planes of bulk gold. A thin oxide layer was created on the gold surface via plasma oxidation, and the thickness and composition of this layer was measured. Clear evidence of a nanometer-thick oxide layer was seen coating the gold tip, and the atomic composition of the oxide layer was consistent with the expected stoichiometry for gold oxide. Monomolecular anions layers of Br(-) and I(-) were created via adsorption from aqueous solutions onto the gold. Atom probe data verified the presence of the monomolecular anion layers on the gold surface, with ion density values consistent with literature values. A hexanethiolate monolayer was coated onto the gold tip, and atom probe analysis revealed a thin film whose ion fragments were consistent with the molecular composition of the monolayer and a surface coverage similar to that expected from literature. Details of the various coating compositions and structures are presented, along with discussion of the reconstruction issues associated with properly analyzing these thin-film systems. PMID- 20575557 TI - Formation of aminyl radicals on electron attachment to AZT: abstraction from the sugar phosphate backbone versus one-electron oxidation of guanine. AB - Employing electron spin resonance (ESR) spectroscopy, we have characterized the radicals formed in 3'-azido-3'-deoxythymidine (3'-AZT) and in its 5'-analog 5' azido-5'-deoxythymidine (5'-AZT) after electron attachment in gamma-irradiated aqueous (H(2)O or D(2)O) glassy (7.5 M LiCl) systems. ESR spectral studies and theoretical calculations show that the predominant site of electron capture in 3' AZT and in 5'-AZT is at the azide group and not at the thymine moiety. The azide group in AZT is therefore more electron affinic than the most electron affinic DNA base, thymine. Electron attachment to 3'-AZT and 5'-AZT results in an unstable azide anion radical intermediate (RN(3)*(-)) that is too short-lived to be observed in our work even at 77 K. At 77 K, we observe the neutral aminyl radical (RNH*) after loss of N(2) from RN(3)*(-) followed by protonation of nitrene anion radical (RN*(-)) to give RNH*. The expected RN*(-) intermediate is not observed as protonation from water is complete at 77 K even under highly basic conditions. Formation of RND* in D(2)O solutions confirms water as the source of the NH proton in the RNH*. Our assignments to these radicals are aided by DFT calculations for hyperfine coupling constants that closely match the experimental values. On annealing to higher temperatures (ca. 160-170 K), RNH* undergoes bimolecular hydrogen abstraction reactions from the thymine methyl group and the sugar moiety resulting in the formation of the thymine allyl radical (UCH(2)*) and two sugar radicals, C3'* and C5'*. RNH* also results in one electron oxidation of the guanine base in 3'-AZG. This work provides a potential mechanism for the reported radiosensitization effects of AZT. PMID- 20575563 TI - One-pot synthesis and optical property of copper(I) sulfide nanodisks. AB - Copper(I) sulfide (Cu(2)S) nanodisks with controllable size and aspect ratio have been synthesized by using a one-pot colloidal process, in which no pre-prepared organometallic precursors are required. The reaction involves the injection of dodecanethiol into a hot solution containing copper salt, surfactants, and a high boiling-point organic solvent. Copper thiolate forms at the beginning of the reaction which effectively acts as a precursor whose decomposition leads to further nucleation and growth of Cu(2)S nanocrystals. The nanocrystals begin as small nanodots in the early stages of the reaction, gradually turning into nanodisks with aspect ratios (average disk diameter divided by thickness) up to 2.0, while the band gap of the nanocrystals decreases accordingly. As the growth of nanocrystals follows the monomer addition mechanism, the diameter, thickness, aspect ratio, and optical property of the Cu(2)S nanodisks can be tuned systematically by changing the reaction time, the amount of surfactants, and the concentration of the precursors. This synthesis provides a simple and highly reproducible method for the preparation of Cu(2)S nanocrystals that may find potential applications in the fabrication of photovoltaic devices. PMID- 20575562 TI - Characterization of membrane protein non-native states. 2. The SDS-unfolded states of rhodopsin. AB - Little is known about the molecular nature of residual structure in unfolded states of membrane proteins. A screen of chemical denaturants to maximally unfold the mammalian membrane protein and prototypic G protein coupled receptor rhodopsin, without interference from aggregation, described in an accompanying paper (DOI 10.1021/bi100338e ), identified sodium dodecyl sulfate (SDS), alone or in combination with other chemicals, as the most suitable denaturant. Here, we initiate the biophysical characterization of SDS-denatured states of rhodopsin. Using absorption, steady-state and time-resolved fluorescence spectroscopy, dynamic light scattering, and cysteine accessibility studies, tertiary structure of denatured states was characterized. In agreement with the pattern of secondary structure changes detected by circular dichroism described in the accompanying paper (DOI 10.1021/bi100338e ), tertiary structure changes are distinct over four SDS concentration ranges based on the expected predominant micellar structures. Dodecyl maltoside (DM)/SDS mixed micelle spheres (0.05-0.3% SDS) turn into SDS spheres (0.3-3% SDS) that gradually (3-15% SDS) become cylindrical (above 15% SDS). Denatured states in SDS spheres and cylinders show a relatively greater burial of cysteine and tryptophan residues and are more compact as compared to the states observed in mixed micellar structures. Protein structural changes at the membrane/water interface region are most prominent at very low SDS concentrations but reach transient stability in the compact conformations in SDS spheres. This is the first experimental evidence for the formation of a compact unfolding intermediate state with flexible surface elements in a membrane protein. PMID- 20575565 TI - Method for characterizing nanoscale wear of atomic force microscope tips. AB - Atomic force microscopy (AFM) is a powerful tool for studying tribology (adhesion, friction, and lubrication) at the nanoscale and is emerging as a critical tool for nanomanufacturing. However, nanoscale wear is a key limitation of conventional AFM probes that are made of silicon and silicon nitride (SiNx). Here we present a method for systematically quantifying tip wear, which consists of sequential contact-mode AFM scans on ultrananocrystalline diamond surfaces with intermittent measurements of the tip properties using blind reconstruction, adhesion force measurements, and transmission electron microscopy (TEM). We demonstrate direct measurement of volume loss over the wear test and agreement between blind reconstruction and TEM imaging. The geometries of various types of tips were monitored over a scanning distance of approximately 100 mm. The results show multiple failure mechanisms for different materials, including nanoscale fracture of a monolithic Si tip upon initial engagement with the surface, film failure of a SiNx-coated Si tip, and gradual, progressive wear of monolithic SiNx tips consistent with atom-by-atom attrition. Overall, the method provides a quantitative and systematic process for examining tip degradation and nanoscale wear, and the experimental results illustrate the multiple mechanisms that may lead to tip failure. PMID- 20575564 TI - Nanoglycan complex formulation extends VEGF retention time in the lung. AB - To extend the retention time of aerosol-delivered growth factors in the lung for stem cell homing/activation purposes, we examined a formulation of vascular endothelial growth factor (VEGF) complexed to dextran sulfate (DS) and chitosan (CS) polyelectrolytes. Optimal incorporation of VEGF was found at a VEGF/DS/CS ratio of 0.12:1:0.33, which resulted in nanoparticle complexes with diameters of 612+/-79 nm and zeta potentials of -31+/-1 mV. The complexes collapsed in physiological solution, and released VEGF in a biphasic time course in vitro. In rat lungs, however, VEGF delivered in the complex was cleared at a constant exponential decay rate, 8-fold slower than that delivered in free form. The extended VEGF retention was likely due to equilibrium binding of VEGF to DS and to endogenous glycosaminoglycans. A similar retention effect is expected with other glycosaminoglycans-binding proteins (including many growth factors) when complexed with these glycans. Owing to its unique application, this type of complex is, perhaps, better described as a nanoglycan complex. PMID- 20575566 TI - Selection of a multi-stage system for biosolids management applying genetic algorithm. AB - An economic analysis and feasibility study of a sequential biosolids management process was developed and tested using Genetic Algorithm (GA). The algorithm was used to identify trends and behaviors of the "Biosolids Process Train". This heuristic method of analysis is robust in that it will not only simulate different design scenarios, its analysis will also suggest possible solutions which meet predetermined requirements. This concept was adopted because GA's biggest advantage is the capability to analyze multiple objective functions, design variables, and constraints. The range of "good approximations" provided by the GA solutions could be useful for municipal wastewater planners who need to search for potential alternatives and evaluate new technologies for managing biosolids. The unit processes in the model were arranged sequentially so the effect modifications to thickening and dewatering parameters could easily be observed further along in the process. The model was extended to examine the supernatant return flow quality and the potential impact on the wastewater treatment plant. Results from a sensitivity analysis on operating expenses reveals the impact that fluctuations in fuel, electricity, and labor costs can have on the total biosolids management cost as well as the selection of the appropriate treatment sequence. PMID- 20575567 TI - Linear dsDNA partitions spontaneously into the inverse hexagonal lyotropic liquid crystalline phases of phospholipids. AB - Recently, we reported that DNA associated with inverse hexagonal (H(II)) lyotropic liquid crystal phases of the lipid 1,2-dioleoyl-sn-glycero-3 phosphoethanolamine (DOPE) was actively transcribed by T7 RNA polymerase. Our findings suggested that key components of the transcription process, probably the T7 RNA polymerase and the DNA, remained associated with the monolithic H(II) phase throughout transcription. Here, we investigate the partitioning of DNA between an H(II) lyotropic liquid crystal phase and an isotropic supernatant phase in order to develop insights into the localization of DNA in liquid crystalline environments. Our results show that linear double stranded DNA (dsDNA) molecules partition spontaneously into monolithic preformed H(II) liquid crystal phases of DOPE. We propose that this process is driven by the increase in entropy due to the release of counterions from the DNA when it inserts into the aqueous pores of the H(II) phase. PMID- 20575569 TI - Neutron and beta/gamma radiolysis of water up to supercritical conditions. 2. SF(6) as a scavenger for hydrated electron. AB - SF(6) has been used as a specific scavenger to investigate the beta/gamma radiolysis yield of hydrated electrons in pressurized high temperature sub- and supercritical water. SF(6) is thermally stable in supercritical water, and each scavenging reaction is known to produce six fluoride ions, which can be readily measured using a fluoride-selective electrode. Problems in the application of this method are described, including buildup of acid product and chain reduction of SF(6) in the presence of organic (*)H and (*)OH radical scavengers. Ultimately we find that the combination of SF(6) and phenol in neutral solution gives reliable results in supercritical water, because the protons and fluoride ions remain associated as HF molecules. The beta/gamma yields in supercritical water are similar to previous measurements using N(2)O scavenger. PMID- 20575568 TI - Selenium speciation in whole sediment using X-ray absorption spectroscopy and micro X-ray fluorescence imaging. AB - A field survey was conducted in a freshwater lake system in the Athabasca Basin, northern Saskatchewan, Canada that receives treated metal mining and milling process effluent containing elevated levels of selenium. Whole sediment, pore water, surface water, and chironomid larvae were analyzed in an attempt to link whole sediment selenium speciation to various environmental factors, including selenium availability to benthic macro-invertebrates, a trophic level through which selenium can enter the diet of higher trophic level organisms. Speciation was measured using synchrotron-based selenium K-edge X-ray absorption spectroscopy (XAS). All lake averages of sediment samples (reference or exposure sites) contained a significant proportion (approximately 50%) of elemental selenium which is relatively insoluble in water, immobile, and not considered to be bioavailable. The presence of elemental selenium was confirmed by extended X ray absorption fine structure (EXAFS) analysis of select samples. Inorganic metal selenides were also found in whole sediment samples and confirmed using micro X ray fluorescence imaging. Dissolved selenium concentrations in pore water were correlated to the amount of selenite in whole sediments provided that the sites were classified according to whole sediment sand content. Sand content itself is likely inversely correlated to sediment organic matter content, adsorption sites, and redox potential. PMID- 20575570 TI - Stoichiometry, vibrational modes, and structure of niobium(V) oxosulfato complexes in the molten Nb(2)O(5)-K(2)S(2)O(7)-K(2)SO(4) system studied by Raman spectroscopy. AB - The structural and vibrational properties of NbV oxosulfato complexes formed in Nb2O5-K2S2O7 and Nb2O5-K2S2O7-K2SO4 molten mixtures with 0 C2n-; a simple formalism exploiting the relative Raman band intensities is used for determining the stoichiometric coefficient, n, pointing to n = 3 and to the following reaction: Nb2O5 + 3S2O72- --> 2NbO(SO4)33 , which is consistent with the Raman spectra of the molten mixtures. Nb2O5 could be dissolved much easier when K2SO4 was present in an equimolar (1:1) SO42-/Nb ratio; the incremental presence of K2SO4 in Nb2O5-K2S2O7 melts induces composition effects in the Raman spectra that terminate when n(SO42-)/n(Nb) = 1. The composition effects and the temperature-dependent features of the Raman spectra obtained for Nb2O5-K2S2O7-K2SO4 molten mixtures together with the spectral changes occurring upon freezing are accounted for by a Nb2O5.3K2S2O7.2K2SO4 stoichiometry for the complete reaction taking place: Nb2O5 + 3S2O72- + 2SO42- --> NbO(SO4)4S2O77- + NbO2(SO4)23-. The spectral data are discussed in terms of the most plausible structural models, for which consistent band assignments are made. The most characteristic Raman bands for the NbV oxosulfato complexes pertain to Nb=O modes: (i) at 937 cm-1 for the mono-oxo Nb=O mode of NbO(SO4)33-; (ii) at 958 cm-1 for the mono-oxo Nb=O mode of NbO(SO4)4S2O77-; and (iii) at 926 cm-1 for the symmetric dioxo Nb(=O)2 mode of NbO2(SO4)23-. PMID- 20575571 TI - Quantum chemistry of C(3)H(6)O molecules: structure and stability, isomerization pathways, and chirality changing mechanisms. AB - Electronic structure calculations were carried out to study the various isomers of formula C(3)H(6)O, as a part of our current quantum chemical and dynamical approaches to intra- and intermolecular kinetics for the C(n)H(2n)O (n = 1, 2, 3) molecules. The usefulness of the GRRM (global reaction route mapping) program developed by Ohno and Maeda in predicting the structure of all isomers and of the transition states connecting them is fully exploited. All the isomers are identified as local minima on the MP2/CC-PVDZ potential energy surface. Acetone is the most stable isomer. In increasing order of stability the others are propanal, 2-propenol, 1-propenol, allyl alcohol, methyl vinyl ether, cyclopropanol, propylene oxide, and oxetane. Various isomerization paths connecting them are identified. All the transition states are fully characterized using intrinsic reaction coordinate calculations. The isomerization reactions may proceed through a single step or involve an intermediate species which is either a carbene or a diradical. Special attention is devoted to propylene oxide, a favorite molecule in current photochemical and stereodynamical studies because of its chiral nature. It is a rigid molecule, and chirality switching is found to be supported by its isomers. Two different chirality switching mechanisms which are assisted by propanal and allyl alcohol are presented. PMID- 20575572 TI - Labdanes and sucrose esters from Physalis sordida. AB - Eight new compounds, labdanes 2-4, homoergostane 10, and sucrose esters 12-15, were isolated from aerial parts of Physalis sordida together with several known compounds. Structures of the new compounds were elucidated using spectroscopic evidence and chemical transformations. The structure of 10 was confirmed by X-ray crystallographic analysis of its methyl ester. Anti-inflammatory activity of compounds 1, 2, 4, 5, and 12-15 was evaluated using the TPA-induced mouse ear edema test. Compounds 12 (IC(50) 0.26 mumol/ear) and 15 (IC(50) 0.24 mumol/ear) showed anti-inflammatory activity similar to that of indomethacin (IC(50) 0.24 mumol/ear). PMID- 20575573 TI - Triplet States and electronic relaxation in photoexcited graphene quantum dots. AB - Electronic relaxation in photoexcited graphenes is central to their photoreactivity and their optoelectrical applications such as photodetectors and solar cells. Herein we report on the first ensemble studies of electronic energy relaxation pathways in colloidal graphene quantum dots with uniform size. We show that the photoexcited graphene quantum dots have a significant probability of relaxing into triplet states and emit both phosphorescence and fluorescence at room temperature, with relative intensities depending on the excitation energy. Because of the long lifetime and reactivity of triplet electronic states, our results could have significant implications for applications of graphenes. PMID- 20575575 TI - Hydrolysis of TiCl(4): initial steps in the production of TiO(2). AB - The hydrolysis of titanium tetrachloride (TiCl(4)) to produce titanium dioxide (TiO(2)) nanoparticles has been studied to provide insight into the mechanism for forming these nanoparticles. We provide calculations of the potential energy surfaces, the thermochemistry of the intermediates, and the reaction paths for the initial steps in the hydrolysis of TiCl(4). We assess the role of the titanium oxychlorides (Ti(x)O(y)Cl(z); x = 2-4, y = 1, 3-6, and z = 2, 4, 6) and their viable reaction paths. Using transition-state theory and RRKM theory, we predicted rate constants including the effect of tunneling. Heats of formation at 0 and 298 K are predicted for TiCl(4), TiCl(3)OH, TiOCl(2), TiOClOH, TiCl(2)(OH)(2), TiCl(OH)(3), Ti(OH)(4), and TiO(2) using the CCSD(T) method with correlation consistent basis sets extrapolated to the complete basis set limit and compared with the available experimental data. Clustering energies and heats of formation are calculated for neutral clusters. The calculated heats of formation were used to study condensation reactions that eliminate HCl or H(2)O. The reaction energy is substantially endothermic if more than two HCl molecules are eliminated. The results show that the mechanisms leading to formation of TiO(2) nanoparticles and larger ones are complicated and will have a strong dependence on the experimental conditions. PMID- 20575574 TI - Immobilization and one-dimensional arrangement of virus capsids with nanoscale precision using DNA origami. AB - DNA origami was used as a scaffold to arrange spherical virus capsids into one dimensional arrays with precise nanoscale positioning. To do this, we first modified the interior surface of bacteriophage MS2 capsids with fluorescent dyes as a model cargo. An unnatural amino acid on the external surface was then coupled to DNA strands that were complementary to those extending from origami tiles. Two different geometries of DNA tiles (rectangular and triangular) were used. The capsids associated with tiles of both geometries with virtually 100% efficiency under mild annealing conditions, and the location of capsid immobilization on the tile could be controlled by the position of the probe strands. The rectangular tiles and capsids could then be arranged into one dimensional arrays by adding DNA strands linking the corners of the tiles. The resulting structures consisted of multiple capsids with even spacing (approximately 100 nm). We also used a second set of tiles that had probe strands at both ends, resulting in a one-dimensional array of alternating capsids and tiles. This hierarchical self-assembly allows us to position the virus particles with unprecedented control and allows the future construction of integrated multicomponent systems from biological scaffolds using the power of rationally engineered DNA nanostructures. PMID- 20575576 TI - Organocatalytic enantioselective olefin aminofluorination. AB - Chiral beta-fluoroamines are increasingly prevalent in medicinal compounds, but there are few efficient methods to access them from achiral starting materials. To address this, a multicomponent organocascade reaction was developed in which chiral alpha-fluoro-beta-amino aldehydes were generated in a single flask from achiral alpha,beta-unsaturated aldehydes (2), using catalyst 12a. Conversions up to 85%, dr's up to 98:2 and ee's up to 99% of the corresponding alcohol (9) were achieved in this reaction. PMID- 20575577 TI - Self-assembly of block copolymer micelles: synthesis via reversible addition fragmentation chain transfer polymerization and aqueous solution properties. AB - Poly(hexafluorobutyl methacrylate) (PHFBMA) homopolymer was synthesized by reversible addition-fragmentation chain transfer (RAFT)-mediated living radical polymerization in the presence of cyano-2-propyl dithiobenzoate (CPDB) RAFT agent. A block copolymer of PHFBMA-poly(propylene glycol acrylate) (PHFBMA-b PPGA) with dangling poly(propylene glycol) (PPG) side chains was then synthesized by using CPDB-terminated PHFBMA as a macro-RAFT agent. The amphiphilic properties and self-assembly of PHFBMA-b-PPGA block copolymer in aqueous solution were investigated by dynamic and static light scattering (DLS and SLS) studies, in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). Although PPG shows moderately hydrophilic character, the formation of nanosize polymeric micelles was confirmed by fluorescence and TEM studies. The low value of the critical aggregation concentration exhibited that the tendency for the formation of copolymer aggregates in aqueous solution was very high due to the strong hydrophobicity of the PHFBMA(145)-b-PPGA(33) block copolymer. The combination of DLS and SLS measurements revealed the existence of micellar aggregates in aqueous solution with an association number of approximately 40 +/- 7 for block copolymer micelles. It was also found in TEM observation that there are 40-50 micelles accumulated into one aggregate and these micelles are loosely packed inside the aggregate. PMID- 20575578 TI - Effects of methylation at the 2 position of the cation ring on phase behaviors and conformational structures of imidazolium-based ionic liquids. AB - The proton at the 2 position of the cation ring in imidazolium-based ionic liquids (ILs) strongly interacts with anions; therefore, the methylation at this position (C(2) methylation) causes significant changes in the physicochemical properties of these liquids. We investigated the C(2) methylation effects on the phase behaviors and cation conformations of ILs by calorimetric and Raman spectroscopic measurements, focusing on the pairs of 1-butyl-3-methylimidazolium salt ([C(4)mim]X) and 1-butyl-2,3-dimethylimidazolium salt ([C(4)C(1)mim]X), where X(-) is Cl(-), Br(-), I(-), BF(4)(-), and PF(6)(-). The melting and freezing points of all pairs increased after the C(2) methylation, as reported previously, and the reason for the increase was the overcompensation of the DeltaS(trans) decrease for the DeltaH(trans) decrease. The C(2) methylation also affected the phase behaviors of the ILs. With Raman spectroscopic measurements, all cation conformations in crystalline phases were assigned to trans-trans (TT), gauche-trans (GT), or gauche'-trans (G'T) conformers of the butyl group. Except in [C(4)C(1)mim]BF(4), all crystal-crystal phase transitions of the present samples occurred accompanied by conformational changes among TT, GT, and G'T. For the gas states of [C(4)mim](+) and [C(4)C(1)mim](+), DFT calculations showed that there were hardly any differences in the structures of the butyl group for each set of paired conformers or in the energetic orders among the conformers. On the other hand, the conformer adopted in the crystalline phase differed between [C(4)mim]X and [C(4)C(1)mim]X. In addition, the population of the conformers in the liquid state also differed in each pair. The data from higher frequency Raman spectra suggested that the difference in cation conformation in each pair, for the crystalline and liquid states, was due to the shift in the position of the anion relative to that of the cation. By C(2) methylation, the relative distance between the anion and cation decreased for Cl(-), Br(-), and I(-) salts, but it increased for BF(4)(-) and PF(6)(-) salts. PMID- 20575579 TI - H-bonding-assisted substituent effect. AB - In this paper we investigate the influence of intramolecular noncovalent interaction, i.e., H-bonding and Li-bonding, on the properties of substituents communicating through the resonance (mesomeric) effect in such molecular systems as salicylaldehyde, o-hydroxy Schiff base, o-nitrosophenol, and their lithium analogues. The investigated systems are usually considered as molecular patterns of intramolecular resonance-assisted hydrogen bonds (or its analogues in the case of Li-bonded systems). We show that the relation between intramolecular noncovalent interactions, A-H...B and A-Li...B, and the pi-electron delocalization in the sequence of pi-conjugated covalent bonds linking A and B can be considered in terms of the Hammett-like substituent effect in which electron-donating and electron-withdrawing properties of substituents are affected by the noncovalent interaction. PMID- 20575580 TI - "One-step" detection of matrix metalloproteinase activity using a fluorogenic peptide probe-immobilized diagnostic kit. AB - Matrix metalloproteinases (MMPs) have been shown to be abundant in pathological conditions such as cancer, osteoarthritis (OA), and rheumatoid arthritis (RA). The extent of MMPs detected in biological samples provides important clinical information for diagnosis, prognosis, and therapeutic monitoring of various diseases relating with MMPs. Herein, we developed a new high-throughput MMP diagnostic kit (MMP-D-KIT) based on a 96-well plate by immobilizing MMP-13 specific fluorogenic peptide probes (MMP peptide probe), which is a pair consisting of a near-infrared (NIR) fluorophore (Cy5.5) and a quencher (BHQ-3), onto the biocompatible glycol chitosan (GC) polymer anchored 96-well plate. When MMP enzymes were simply added and incubated in a MMP-D-KIT, the fluorescence of each well was recovered and the fluorescence intensity showed distinct difference within minutes through NIR fluorescence imaging system. The fluorescence was recovered not only by MMP-13 activity, but also by other MMPs activity. Furthermore, recovery of NIR fluorescent signals in MMP-D-KIT was proportional to concentrations of immobilized MMP peptide probe-GC conjugates and, importantly, MMP concentration. The MMP-D-KIT is most specific for target MMP, compared with other enzymes including caspase-3 and 20s proteasome. Additionally, the MMP-D-KIT was used to detect MMP activity in biological samples such as synovial fluid from 12 OA patients (grades 1-4 based on the Kellgren-Lawrence grading scale). It was found that the fluorescence intensity measured using MMP-D-KIT decidedly correlates with the progression of OA. The MMP-D-KIT could be applicable in detecting MMP activities in various biological samples and evaluating the effects of MMP inhibitors in a rapid and easy fashion. PMID- 20575581 TI - Feedback regulated drug delivery vehicles: carbon dioxide responsive cationic hydrogels for antidote release. AB - A possible approach to handling the harmful side effects of an analgesic overdose, without losing its therapeutic potential, involves feedback regulated delivery of an antidote. For example, overdose of morphine causes hypoventilation, an inadequate ventilation to perform gas exchanges in lungs leading to increased CO2 concentration in the blood. Taking advantage of CO2 as a toxicity marker, a hydrogel-based delivery vehicle containing dimethylamino groups [poly(N,N-dimethylaminoethyl methacrylate) cross-linked by trimethylolpropane trimethacrylate] was designed. Stimulus controlled swelling of these hydrogels in naloxone delivery is discussed. A remarkable control over naloxone release was achieved against the concentration of the biomarker. The overall stimuli response of the gel could be enhanced further by encapsulating carbonic anhydrase, a metalloenzyme known to catalyze the reversible hydration of CO2. Thus, a feedback regulated drug delivery vehicle based on toxicity biomarker strategy was modeled successfully, which has the potential to mitigate risks associated with drug overdose. PMID- 20575582 TI - Methyl cation affinities of neutral and anionic maingroup-element hydrides: trends across the periodic table and correlation with proton affinities. AB - We have computed the methyl cation affinities in the gas phase of archetypal anionic and neutral bases across the periodic table using ZORA-relativistic density functional theory (DFT) at BP86/QZ4P//BP86/TZ2P. The main purpose of this work is to provide the methyl cation affinities (and corresponding entropies) at 298 K of all anionic (XH(n-1)(-)) and neutral bases (XH(n)) constituted by maingroup-element hydrides of groups 14-17 and the noble gases (i.e., group 18) along the periods 2-6. The cation affinity of the bases decreases from H(+) to CH(3)(+). To understand this trend, we have carried out quantitative bond energy decomposition analyses (EDA). Quantitative correlations are established between the MCA and PA values. PMID- 20575583 TI - Influence of linker geometry on uranyl complexation by rigidly linked bis(3 hydroxy-N-methyl-pyridin-2-one). AB - A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long (alpha,alpha'-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular N(amide)-O(phenolate) distances and (1)H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding. PMID- 20575584 TI - Pincer phosphine complexes of ruthenium: formation of Ru(P-O-P)(PPh3)HCl (P-O-P = xantphos, DPEphos, (Ph2PCH2CH2)2O) and Ru(dppf)(PPh3)HCl and characterization of cationic dioxygen, dihydrogen, dinitrogen, and arene coordinated phosphine products. AB - Treatment of Ru(PPh(3))(3)HCl with the pincer phosphines 9,9-dimethyl-4,5 bis(diphenylphosphino)xanthene (xantphos), bis(2-diphenylphosphinophenyl)ether (DPEphos), or (Ph(2)PCH(2)CH(2))(2)O affords Ru(P-O-P)(PPh(3))HCl (xantphos, 1a; DPEphos, 1b; (Ph(2)PCH(2)CH(2))(2)O, 1c). The X-ray crystal structures of 1a-c show that all three P-O-P ligands coordinate in a tridentate manner through phosphorus and oxygen. Abstraction of the chloride ligand from 1a-c by NaBAr(4)(F) (BAr(4)(F) = B(3,5-C(6)H(3)(CF(3))(2))(4)) gives the cationic aqua complexes [Ru(P-O-P)(PPh(3))(H(2)O)H]BAr(4)(F) (3a-c). Removal of chloride from 1a by AgOTf yields Ru(xantphos)(PPh(3))H(OTf) (2a), which reacts with water to form [Ru(xantphos)(PPh(3))(H(2)O)H](OTf). The aqua complexes 3a-b react with O(2) to generate [Ru(xantphos)(PPh(3))(eta(2)-O(2))H]BAr(4)(F) (5a) and [Ru(DPEphos)(PPh(3))(eta(2)-O(2))H]BAr(4)(F) (5b). Addition of H(2) or N(2) to 3a c yields the thermally unstable dihydrogen and dinitrogen species [Ru(P-O P)(PPh(3))(eta(2)-H(2))H]BAr(4)(F) (6a-c) and [Ru(P-O-P)(PPh(3))(N(2))H]BAr(4)(F) (7a-c), which have been characterized by multinuclear NMR spectroscopy at low temperature. Ru(PPh(3))(3)HCl reacts with 1,1'-bis(diphenylphosphino)ferrocene (dppf) to give the 16-electron complex Ru(dppf)(PPh(3))HCl (1d), which upon treatment with NaBAr(4)(F), affords [Ru(dppf){(eta(6)-C(6)H(5))PPh(2)}H]BAr(4)(F) (8), in which the PPh(3) ligand binds eta(6) through one of the PPh(3) phenyl rings. Reaction of 8 with CO or PMe(3) at elevated temperatures yields the 18 electron products [Ru(dppf)(PPh(3))(CO)(2)H]BAr(F)(4) (9) and [Ru(PMe(3))(5)H]BAr(4)(F) (10). PMID- 20575585 TI - Spontaneous symmetry breaking during self-assembly of a double stranded biphenolate-based Ti(IV)-helicate. AB - A binuclear Ti(IV)-based helicate synthesized from a symmetric tetrahydroxyheptaphenylene strand was self-assembled in solution and shown to undergo a spontaneous head-to-tail differentiation according to single-crystal X ray diffraction. PMID- 20575586 TI - A highly convergent synthesis of tricyclic N-heterocycles coupling an Ugi reaction with a tandem S(N)2'-Heck double cyclization. AB - A small library of natural product-like compounds has been assembled by coupling an Ugi multicomponent reaction with two postcondensation transformations, carried out in one-pot fashion: a S(N)2' cyclization followed by an intramolecular Heck reaction. PMID- 20575587 TI - Conformational studies on the Delta8(E,Z)-sphingolipid desaturase from Helianthus annuus with chiral fluoropalmitic acids as mechanistic probes. AB - The Delta(8)-sphingolipid desaturase from sunflower (Helianthus annuus) converts phytosphinganine into a mixture of Delta(8)-(E)- and -(Z)-phytosphingenines by removal of two syn-hydrogen atoms from anti-, and gauche-conformations of the substrate. With chiral (R)-6-, (S)-6-, (R)-7-, and (S)-7-fluoropalmitic acids the importance of conformations for the formation of (E)- and (Z)-isomers was investigated by using growing yeast cells expressing the desaturase from H. annuus. The fluoropalmitic acids were readily incorporated into a series of fluorinated phytosphinganines. The desaturation products of the major C(18) fluorophytosphinganine demonstrate that different conformations of the relevant aliphatic segment of the sphingolipids can be exposed to the active center of the enzyme resulting in (E)- or (Z)-fluoroalkenes. The presence of a fluorine atom at the position of the initial hydrogen removal C8-H(R) led to a complete suppression of the desaturation reaction, while replacement of C8-H(S) with fluorine generated a mixture of mainly (Z)- and trace amounts of (E) fluoroolefine. Fluorine at C9 of the phytosphinganine precursors did not interfere with the initial C-H activation step and produced (E)- and (Z) fluoroalkenes in the same ratio as observed for the nonfluorinated precursors. Hydroxylated byproducts of the desaturation process were not observed. These results strongly support the importance of conformations of the transition states during desaturation as the relevant criterion for the relative ratio of (E)- and (Z)-alkenes. PMID- 20575588 TI - Stability of spherical vesicles in electric fields. AB - The stability of spherical vesicles in alternating (ac) electric fields is studied theoretically for asymmetric conductivity conditions across their membranes. The vesicle deformation is obtained from a balance between the curvature elastic energies and the work done by the Maxwell stresses. The present theory describes and clarifies the mechanisms for the four types of morphological transitions observed experimentally on vesicles exposed to ac fields in the frequency range from 500 to 2 x 10(7) Hz. The displacement currents across the membranes redirect the electric fields toward the membrane normal to accumulate electric charges by the Maxwell-Wagner mechanism. These accumulated electric charges provide the underlying molecular mechanism for the morphological transitions of vesicles as observed on the micrometer scale. PMID- 20575590 TI - Controlled synthesis of linear alpha-cyclodextrin oligomers using copper catalyzed Huisgen 1,3-dipolar cycloaddition. AB - The design and efficient synthesis of a novel class of linear oligomers based on cyclodextrins are described. These supramolecules have relatively rigid structures with well-defined topology and sizes, which could provide them with the ability to be used as scaffolds to present bioactive molecules to their receptors as well as host molecules. PMID- 20575589 TI - A bastadin with potent and selective delta-opioid receptor binding affinity from the Australian sponge Ianthella flabelliformis. AB - Three new bastadins, bastadin 25 (1), 15-O-sulfonatobastadin 11 (2), and bastadin 26 (3), were isolated from a MeOH extract of the Australian marine sponge Ianthella flabelliformis. Their structures were determined by interpretation of 1D and 2D NMR spectra and mass spectrometry. Bastadin 26 (3) showed potent affinity for the guinea pig delta-opioid receptors with a K(i) value of 100 nM. The other two bastadins had a 100-fold lower affinity. The three compounds were also tested for their affinity to guinea pig micro- and kappa-opioid receptors and shown to have either no affinity or only very weak affinity toward both of these opioid receptors. PMID- 20575591 TI - An acyclic trialkylamine virtually planar at nitrogen. Some chemical consequences of nitrogen planarity. AB - The synthesis of the exceedingly congested amine tris(1,3-dihydroxy-2 propyl)amine, 9, was achieved in 47- 51% overall yield. The nitrogen atom of 9 is virtually planar; it is 0.082 A out of the plane defined by the three attached carbons. The corresponding out-of-plane measurement is 0.282 A for triisopropylamine and ca. 0.4 A for uncongested trialkylamines. The N-C bonds of 9 are quite short, despite the steric congestion. The conjugate acid of 9 (viz., 9H(+)) is very strong: pK(a) = 3.08 (cf. Et(3)NH(+) pK(a) = 10.7). Comparison with suitable model compounds suggests 9 is less basic than predicted by ca. 1.5 pK(a) units. The structure of 9H(+)Cl(-) was determined by X-ray crystallography. Here too, the nitrogen is severely flattened relative to ordinary ammonium cations. In 9H(+)Cl(-), the proton on the nitrogen of 9H(+) forms three intramolecular hydrogen bonds to hydroxyl groups, i.e., a so-called trifurcated hydrogen bond. The NH...O lengths in 9H(+) are slightly shorter than comparable trifurcated hydrogen bonds. Cyclic voltammetry (CV) on 9 finds E(1/2)(ox) is 0.88 V, which is consistent with the inductive effect of the 1,3-dihydroxy-2-propyl groups attached to nitrogen. It is also observed that the electrochemical oxidation of 9 is reversible on the CV time scale. The (15)N NMR chemical shift of the essentially planar nitrogen atom of 9 is discussed. PMID- 20575593 TI - Hepatocyte growth factor (HGF): a predictor of outcome and response to therapy in hepatitis C? PMID- 20575592 TI - Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV. AB - BACKGROUND: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. OBJECTIVE: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency. METHODS: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. RESULTS: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. CONCLUSIONS: Our results suggest that prospective HLA B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care. PMID- 20575594 TI - Serum oxidative stress is increased in patients with post cholecystectomy bile duct injury. AB - BACKGROUND: Post-cholecystectomy bile duct injuries are identified by the onset of jaundice as well as elevated bilirubin and alkaline phosphatase levels during the peri-operative period. It is unknown how serum oxidative stress markers are modified in patients with post-cholecystectomy bile duct injuries. OBJECTIVE: To determine serum oxidative stress marker levels (lipid peroxidation by-products, nitrites/nitrates and total antioxidant capacity) in patients with post cholecystectomy bile duct injuries. PATIENTS AND METHODS: A prospective, transversal and analytical study was designed with two groups. Group 1: 5 healthy volunteer subjects. Group 2: 52 patients with post-cholecystectomy bile duct injuries (43 female and 9 male). An elective bilio-digestive reconstruction was performed at week 8. The serum oxidative stress marker levels were quantified by colorimetric method. RESULTS: Patients with bile duct injuries had a significant increased serum lipid peroxides (malondialdehyde and 4-hydroxy-alkenals) and nitric oxide metabolites (nitrites/nitrates) levels compared to the control group. In contrast, total antioxidant capacity in patients with bile duct injuries remained similar compared to healthy controls. CONCLUSIONS: The results show that oxidative stress is usually associated to bile duct injury. PMID- 20575595 TI - Minilaparoscopic-assisted transvaginal approach in benign liver lesions. AB - OBJECTIVE: To report two benign liver lesions treatment under minilaparoscopic assisted transvaginal approach. PATIENTS AND METHODS: Females, 44 and 45 years old, respectively, were treated. Patient 1 showed a 1,2 cm O tumor located in the left liver lobe. In preoperative studies was not possible to discern the etiology, for what was decided surgical treatment. The patient 2 showed a symptomatic liver simple cyst, 8 cm O, located in the subsegment VI. She refused percutaneous treatment, it was recommended surgical treatment under general anesthesia. The surgical intervention offered was either the laparoscopic or the transvaginal approach, but this latter was accepted. Pneumoperitoneum with 15 mmHg was used. Two small trocars were inserted into the abdomen. The first one (5 mm O) at the umbilical region, the second one (3 mm O) near the lesion. One trocar 11 mm O, was placed in the posterior cul-de-sac. In patient 1 a large dissector was introduced adjacent to the trocar. In the patient 2, one second trocar 5 mm O was introduced in vagina for operative instruments. Both specimens were extracted through the vagina, protected in extractor bags. VARIABLES STUDIED: operating room time; analgesia required and post-operative complications. RESULTS: The operating room times were 51 and 73 min, respectively. Only the patient with hepatic liver cyst required post-operative analgesia for pain at the right upper quadrant. Both patients were discharged before 24 hours. No postsurgical complications were found in the 6 months follow up. CONCLUSIONS: Using transvaginal approach assisted with minilaparoscopy was possible to carry out surgical treatment in benign and non complex liver lesions located in outlying subsegments. It is a safe method with better aesthetic result than laparoscopic surgery. Nevertheless, will be necessary future studies that demonstrate the advantages of this approach in the hepatic lesions. PMID- 20575596 TI - Hepatocyte growth factor and chronic hepatitis C. AB - OBJECTIVE: The hepatocyte growth factor (HGF) is a pleiotropic cytokine produced by hepatic stellate cells and implicated in liver regeneration and fibrosis. Serum levels of HGF vary in liver diseases, reflecting hepatic damage and hepatocellular dysfunction. In this study, serum levels of HGF and the relationship between HGF and biochemical, histological and virological data, have been analysed in patients suffering from chronic hepatitis C (CHC). PATIENTS AND METHODS: Serum HGF concentration was measured by ELISA in sandwich in 45 patients with CHC. Correlation between HGF levels and histological (necroinflammatory activity and fibrosis score) and biochemical (transaminases, prothrombin activity, albumin, bilirubin), or virological (hepatitis C virus load) parameters was analyzed. Serum HGF concentration was also studied in a subgroup of the original sample treated with interferon and ribavirin. RESULTS: Sserum HGF concentrations of patients with CHC were significantly higher than those detected in healthy controls. Patients with significant fibrosis (F > or = 2) had a significantly older age, lower count of platelets and higher values of AST, GGT and HGF, than those patients with a fibrosis score F < 2. HGF concentration was identified by multivariate analysis as the only independent factor associated with significant fibrosis. Moreover, area under receiver operating curve, using HCG levels, showed similar values to those of previously validated non-invasive indexes of fibrosis. However, levels of HGF did not show a significant decrease in patients with a sustained response to anti-virus C therapy. CONCLUSION: Serum HGF concentration correlates with fibrosis score in patients with CHC, but is insensitive to monitor changes induced by anti-virus C therapy. PMID- 20575597 TI - Low serological positivity in patients with histology compatible with celiac disease in Peru. AB - OBJECTIVE: To study the frequency of positive serology for celiac disease (CD) in patients with duodenal biopsies suggestive of this disease. MATERIAL AND METHODS: Cross sectional study. We included patients with duodenal biopsies histologically compatible with CD and antigliadin, antiendomysial and IgA antitransglutaminase antibodies. We defined a "case" of CD if there was a positive biopsy and either antiendomisial or antitransglutaminase positive antibodies. RESULTS: Thirty one patients were included in our study. Six were antiendomysial positive and 5 antitransglutaminase positive while the antigliadin was positive in 14 cases. Therefore, out of 31 patients only 10 had a serology compatible with CD and only one had positive both antibodies, antiendomysial and antitransglutaminase. CONCLUSIONS: a) We have found that most of the duodenal biopsies compatible with CD are not diagnosed with positive serology; and b) we found a low correlation between serological diagnostic tests. PMID- 20575598 TI - Corelation among clinical, biochemical and tomographic criteria in order to evaluate the severity in acute pancreatitis. AB - BACKGROUND: The acute pancreatitis is an inflammatory process that may involve peripancreatic tissue and distant organs. According to the Atlanta criteria, in 10 to 20% of the patients the disease is severe. Nowadays there are different clinical and biochemical severity scales such as the Ranson, APACHE-II (Acute Physiology and Chronic Health Evaluation) and hematocrit, which have discrepancies when being compared to tomographic scales such as the Balthazar. There exist few studies that correlate these parameters. OBJECTIVE: To evaluate the severity of the acute pancreatitis according to the Ranson, APACHE-II and serous hematocrit criteria at the moment of admission of the patient and correlate these scales with the local pancreatic complications according to the Balthazar classification. PATIENTS AND METHOD: Retrospective, observational and analytic study. There were included patients of any gender above the age of 18, with diagnosis of acute pancreatitis of any etiology, who had performed an abdominal tomography 72 hours after the beginning of the clinical condition in order to stage the pancreatic damage. The diagnosis of acute pancreatitis was established with 2 of the 3 following criteria: a) characteristic abdominal pain; b) uprising of the amylase and/or lipase more than 3 times above the superior normal limit; and c) characteristic finds of acute pancreatitis in the computed tomography. In order to make the correlation, the Pearson or the Spearman tests were used according to the distribution of the variables. RESULTS: There were included 28 patients (21 masculine, 75%). The most frequent etiology was due to alcohol (53.6%, bile (21.4%) and hypertriglyceridemia (17.9%). The age average was 38.1 years old. Fifty per cent of the patients had acute severe pancreatitis according to the Atlanta criteria. Of the patients with APACHE-II less than 8 points, 62.5% were classified according to the Balthazar tomographic scale as D or E degree. Ninety-two point nine per cent of the patients had less than 3 Ranson criteria of which 57.6% got D or E degree. Fifty-seven per cent of the patients with hematocrit value lower than 44% got D and E Balthazar degree, and 64.2% of the patients with hematocrit above 44% got D and E degree.The Pearson correlation (PC) for APACHE-II and Ranson p = 0.013 of 0.476 PC for APACHE-II and Balthazar p = 0.367 of 0.476 and Spearman s correlation p = 0.460 PC for APACHE II and hematocrit p = 1.32 of 0.476. CONCLUSIONS: There does not exist a good correlation between the seriousness scale of Ranson and APACHE-II with the tomographic Balthazar degrees, therefore it is more likely to find very ill patients with an A or B Balthazar and on the other hand patients with acute low pancreatitis with a D or E Balthazar. PMID- 20575599 TI - A retrospective study on a cohort of patients with lymphocytic colitis. AB - OBJECTIVE: The term "microscopic colitis" includes lymphocytic colitis (LC) and collagenous colitis, bearing common clinical presentation distinguishable only by histopathological examination of colonic biopsies. This study reports on demographic and clinical characteristics, and outcome of a cohort of patients with LC. METHODS: Demographic, clinical and histopathological data were reviewed. Every patient underwent total colonoscopy with multiple biopsies examined by an expert pathologist. Diagnosis of LC was confirmed if histopathological criteria were present. Routine laboratory tests were collected to rule out other diagnosis. RESULTS: We included 80 patients (28 males; mean age: 46.4 years). At diagnosis, 71 patients (88%) reported diarrhea, 46 (58%) abdominal pain, 21 (36%) weight loss, 10 (13%) nausea. Regarding autoimmune or inflammatory diseases accompanying LC, thyroid disorders and celiac disease (CD) ranked first. Moreover, in over 10% of patients who underwent esophagogastroduodenoscopy, duodenal biopsies showed villi alterations classified as Marsh I damage, without clinical and serological data for diagnosis of CD. Mesalazine and oral topical steroids (budesonide or beclomethasone) were used to treat LC in 34 (43%) and 32 (39%) of patients, respectively, with similar percentages of clinical response (approximately 80%). CONCLUSIONS: The need for total colonoscopy with multiple biopsies in all patients with chronic watery diarrhea was confirmed. Since the association between CD and LC exists, additional tests should be performed in patients not responding to gluten-free diet or to LC specific therapy to exclude the other condition. Mesalazine obtained a similar outcome than oral steroids in this cohort. PMID- 20575600 TI - Clipping of a post-sphincterotomy bleeding. PMID- 20575601 TI - Hemobilia after pseudoaneurysm of a right hepatic artery branch. PMID- 20575602 TI - Gastrointestinal stromal tumors (GISTs) of the colon. AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Although they may arise anywhere of GI tract, colonic presentation is infrequent. We report 2 new cases of colonic GISTs localized at descending and sigmoid colon. Endoscopic biopsies were diagnostic for GISTs and no distant metastasis were observed. Both cases underwent resective surgery as the only treatment. No recurrence was observed during the follow-up period. In this clinical note we review the diagnosis, management and therapeutical options in colonic GISTs, according to literature. KIT immunoreactivity is the base for diagnosis. Risk of malignancy is based on the primary tumor diameter and the mitotic count. Anatomic localization is not an independent prognostic factor. Surgery is the standard treatment for localized primary disease and imatinib is indicated if metastatic or unresectable GISTs. PMID- 20575603 TI - [Patient's information. Extra-gastrointestinal manifestation of the gastroesophageal reflux]. PMID- 20575604 TI - [Primary esophageal malignant melanoma]. PMID- 20575605 TI - [Mantle cell lymphoma involving the gatrointestinal tract: endoscopic features]. PMID- 20575606 TI - Sengstaken-Blakemore tube related esophageal rupture. PMID- 20575607 TI - Dieulafoy's lesion in a duodenal diverticulum successfully treated with N-butyl-2 cyanoacrylate. PMID- 20575608 TI - Gastric lipoma--an unusual cause of upper gastrointestinal bleeding. PMID- 20575609 TI - [Idiopathic thrombocytopenic purpura induced by PEG interferon]. PMID- 20575610 TI - The role of the internet on patient knowledge management, education, and decision making. AB - E-health encompasses a broad range of health disciplines that use the Internet and associated technologies to deliver information and health services. Traditionally, patients have relied on the healthcare professional to provide relevant medical information to inform decision making on diagnosis and therapy. Patient education in the past has consisted of independently collated health information, disseminated predominantly in written and video formats. Greater accessibility to the Internet has provides a novel method for patients to access health information and play a greater role in decisions ultimately affecting their health. However, patients' ability to access, understand, and integrate this knowledge with their healthcare professional influences the extent to which such technologies are effective. This article provides an overview of the impact of the Internet on patient knowledge management, education, and its subsequent impact upon the medical decision-making process between the patient and clinician. PMID- 20575611 TI - Influence of outdoor activity and indoor activity on cognition decline: use of an infrared sensor to measure activity. AB - OBJECTIVE: The increasing number of dementia patients causes serious social problems. Previously, we reported that elderly individuals with cognitive impairment show a low frequency of activity. This study was designed to investigate the correlation of daily activity to the decline in cognitive function. METHODS: The study enrolled 53 elderly who live alone. The cognitive function of subjects was assessed by the mini-mental state examination (MMSE) before the investigation. Passive infrared sensors were installed in the subjects' houses. The subjects' in-house movements were recorded by the sensors for approximately 1 year. The activities of daily life were assessed, based on these records. The subjects' cognitive function was assessed again after the investigation and categorized into two groups: the cognition decline group (MMSE score: <24, n=6) and the normal group (MMSE score: over 24, n=44). The activity parameters were compared between the two groups. RESULTS: The subjects in the cognition decline group had a significantly lower number of outings (8.8 vs. 17.3, p<0.01) and there was no cognition decline in patients in the frequent outings group (over 20 outings per month). In addition, the indoor movement decreased in the cognition decline group during the study period and the indoor movement of the normal group was maintained at the baseline level. CONCLUSIONS: This study objectively evaluated the behavior of elderly individuals with infrared sensors and revealed that elderly people who have few occasions to go out tend to show a decrease in cognitive function. PMID- 20575612 TI - Influence of plasticizer type and level on the properties of Eudragit S100 matrix pellets prepared by hot-melt extrusion. AB - Matrix-type pellets with controlled-release properties may be prepared by hot melt extrusion applying a single-step, continuous process. However, the manufacture of gastric-resistant pellets is challenging due to the high glass transition temperature of most enteric polymers and an unacceptably high, diffusion-controlled drug release from the matrix during the acidic phase. The objective was to investigate the influence of three plasticizers (triethyl citrate, methylparaben and polyethylene glycol 8000) at two levels (10% or 20%) on the properties of hot-melt extruded Eudragit S100 matrix pellets. Extrusion experiments showed that all plasticizers produced similar reductions in polymer melt viscosity. Differential scanning calorimetry and powder X-ray diffraction demonstrated that the solid state plasticizers were present in the amorphous state. The drug release in acidic medium was influenced by the aqueous solubility of the plasticizer. Less than 10% drug was released after 2 h at pH 1.2 when triethyl citrate or methylparaben was used, independent of the plasticizer level. Drug release at pH 7.4 resulted from polymer dissolution and was not influenced by low levels of plasticizer, but increased significantly at the 20% level. Mechanical testing by diametral compression demonstrated the high tensile strength of the hot-melt extruded pellets that decreased when plasticizers were present. PMID- 20575613 TI - Electronic therapeutic contact for adolescent weight management: the Loozit study. AB - OBJECTIVE: To examine adolescent and facilitator participation in the first 10 months of an obesity management intervention including electronic contact (e contact) via e-mail and short message service (SMS) communication. MATERIALS AND METHODS: Participants (n=49) were overweight and obese (13-16 year olds) and were randomized to receive e-contact in the Loozit trial. Adolescents were sent brief, semipersonalized health messages approximately monthly, from 2 to 12 months. We analyzed adolescents' response patterns, reply content, satisfaction with e contact intervention, and facilitator responsiveness. Two coding systems described the general attributes and content of adolescent replies and facilitator responses. RESULTS: Adolescents' overall reply rate was 22%. There was no difference in age, sex, socioeconomic status, body mass index z-score, or initial group program attendance between the 27 adolescents who replied to 0-2 messages and the 22 who replied to >or=3 messages. Adolescent SMS replies had less characters and a quicker response time compared with e-mail replies. Adolescent responses were largely relevant to initial health messages sent (91%), with few using "SMS language" (17%) or emoticons (7%). Most adolescents rated e contact as "somewhat helpful." Facilitators responded to 93% of adolescent replies, and most responses were personalized (93%), encouraging (88%), and educational (75%). CONCLUSIONS: Although adolescent engagement was modest, SMS and e-mail communication is a feasible and acceptable adjunct to group lifestyle intervention and telephone coaching in overweight and obese adolescents. Healthy eating messages and those concluding with "please reply" elicited the highest reply rates, and thus these message types should be included in future adolescent e-contact interventions. PMID- 20575614 TI - Remote monitoring of health status of the elderly at home in Taiwan. AB - This case involves a B2B2C model (service provider to community to the elderly) of innovative tele-care services. The service provider under study is Chu-Shan Show-Chwan Hospital, a district hospital in Nantou County, Taiwan. The community comprises social welfare institutions such as temples, community care centers, and nursing homes. Finally, the elderly individuals who are the ultimate targets of the service are either community residents or residents of nursing homes. The community, as a service promoter, contributes to the increased acceptance of the newly introduced tele-care service compared with the traditional B2C model. Numerous communities under study and some social welfare organizations are extremely interested in providing healthcare services to the elderly and will support future operations provided satisfactory results are achieved. This project can help district hospitals extend their primary care function to communities, build trust, and improve relationships between physicians and patients. PMID- 20575615 TI - Telepsychiatry assessments of child or adolescent behavior disorders: a review of evidence and issues. AB - BACKGROUND: The limited number of mental health specialists for children has led to an increased need for child and adolescent psychiatrists to provide primary care consultations and treatment recommendations. Psychiatric assessments and treatments provided via two-way videoconferencing (telepsychiatry) have been used to increase the availability of child psychiatrists. This article reviews the literature on telepsychiatry assessment of children and adolescents. METHODS: Research on telepsychiatry has focused on the comparability of telepsychiatric treatments to in-person treatment for adult patients. Relatively little research has addressed the ability of telepsychiatric assessments to facilitate favorable treatment outcomes, particularly for child or adolescent patients. This was a literature search using Medline via Ovid. It focused on English-language material published between 1996 and 2009. A range of search terms relating to assessment, mental health, telemedicine, and children was used. Any studies focusing on child and adolescent psychiatric assessment were included. RESULTS: The limited literature on children is usually related to project descriptions or case reports. The studies tend to find acceptance and the diagnoses and recommendations are not seen as different from in-person assessments. Practical considerations that arise in giving telepsychiatric assessments are discussed. CONCLUSION: Although there are significant weaknesses in the research justifying telepsychiatric assessments in children and adolescents, there are no data that suggest that this process contributes to negative outcomes. Details on the setting for telepsychiatry assessments and camera view have not been studied. PMID- 20575616 TI - Comparing face-to-face and telehealth-mediated delivery of a psychoeducational intervention: a case comparison study in hospice. AB - This case study compared the delivery of a psychoeducational intervention with hospice caregivers, delivered in person and via videophone. This study demonstrates the feasibility of using telehealth tools to deliver interventions in hospice and identified ways or protocols that can be adapted for telehealth delivery. The caregiver expressed satisfaction with the telehealth experience, supporting the value of video communication. The results have laid the framework for further implementation of an ongoing, randomized clinical trial examining the use of telehealth tools for delivery of psychoeducational interventions with hospice caregivers. PMID- 20575617 TI - Longer 19-base pair short interfering RNA duplexes rather than shorter duplexes trigger RNA interference. AB - Short interfering RNAs (siRNAs) are valuable reagents for sequence-specific inhibition of gene expression via the RNA interference (RNAi) pathway. Recently, it was suggested that 16-bp siRNAs are effective RNAi triggers and superior to "classical" 19-bp siRNAs. This contradiction with generally accepted knowledge prompted us to reinvestigate this issue. Here, in a series of experiments performed with siRNA duplexes of various lengths (from 19 to 15 bp) designed to silence either overexpressed enhanced green fluorescent protein or endogenously expressed CDK9, we demonstrate that 19-bp siRNAs are more active silencers than shorter corresponding duplexes. The discrepancy between our results and those questioned appears to be due to different modes of shortening the duplex (either at the 3'-end or at the 5'-end, with respect to polarity of the guide strand). Importantly, duplexes with intact 5'-ends but shortened at their 3'-ends retain target site specificity, whereas those shortened at the 5'-end are complementary to different target sites located upstream. PMID- 20575618 TI - Determinants of weight gain in young women: a review of the literature. AB - BACKGROUND: Young adult women (18-36 years) are gaining weight at rates higher than women in other age groups. Given its long-term deleterious health effects, it is important to know the determinants of this weight gain. However, other than in relation to pregnancy, little is known about the determinants of weight gain in this population group. MATERIALS AND METHODS: Papers examining nonpregnancy weight gain in young women were identified through a literature search in PubMed in August 2008. Subsequently, reference lists of included papers were checked for additional eligible papers. RESULTS: A total of 29 papers were included in this review. They were grouped into five categories on the basis of the main identified determinants of weight gain: contraception (4); dietary behaviors (3); quitting smoking (1); physical activity (PA) (1); and university transition (20 papers). Study duration ranged from 13 days to 15 years. Weight was objectively measured in 25 studies and self-reported in 4 studies. Twenty-seven papers reported weight gain; the highest rates were observed with initial exposure to contraceptive use and the first semester of attending a university. CONCLUSIONS: Even though young adulthood is a vulnerable time for weight gain in women, the number of studies examining specific determinants of weight gain was small. Those located identified five social and behavioral determinants, with most of the research focusing on the transition to and through a university, and few studies in nonuniversity populations. More studies are needed to assess the concurrent contributions of multiple determinants of weight gain at this life stage, so that appropriate interventions to prevent excess weight gain can be developed. PMID- 20575619 TI - Interventions to increase mammography rates among U.S. Latinas: a systematic review. AB - BACKGROUND: In the United States, health disparities exist in mammography rates for Latinas compared with other ethnic groups. Additionally, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths among Latina women. Increased mammography rates and earlier breast cancer diagnosis can decrease breast cancer fatality rates among Latina women. METHODS: The purpose of this systematic review was to contribute to the knowledge basis on breast cancer prevention for U.S. Latinas by determining the effectiveness of interventions designed to increase mammography rates among this population. Both experimental and quasi-experimental studies were included in the systematic review, and nine were located that met inclusion criteria. RESULTS: Odds ratios were calculated, and the overall effect indicated a low level of effectiveness. CONCLUSIONS: Implications of findings for practice and research are discussed. PMID- 20575620 TI - Knowledge, preventive action, and barriers to cardiovascular disease prevention by race and ethnicity in women: an American Heart Association national survey. AB - BACKGROUND: Racial and ethnic disparities in cardiovascular disease (CVD) outcomes and risk factors are well documented, but few data have evaluated population differences in CVD knowledge, preventive action, and barriers to prevention. METHODS: A nationally representative sample of 1008 women (17% Hispanic, 22% black, 61% white/other) selected through random digit dialing were given a standardized questionnaire about knowledge of healthy risk factor levels, recent preventive actions, and barriers to prevention. Analysis focused on predictors of knowledge and preventive action in the past year and proportion reporting select barriers to prevention. Logistic regression was used to determine if race/ethnicity was independently associated with knowledge and preventive action after adjustment. RESULTS: No racial/ethnic differences in risk factor knowledge were identified except Hispanic women were 44% less likely than white/others to know the optimal high-density lipoprotein cholesterol (HDL-C) level (odds ratio [OR] 0.56,95% confidence interval [CI] 0.35-0.91). Knowledge of blood pressure goal was lower among those with less than a college education (OR 0.59,95% CI 0.44-0.79). Hispanics were twice as likely as white/others to help someone else lose weight (OR 1.78,95% CI 1.17-2.71) or add physical activity (OR 1.95,95% CI 1.18-3.22) in the past year. Blacks were more likely than whites/others to report decreased unhealthy food consumption (OR 1.77,95% CI 1.08 2.93), trying to lose weight (OR 1.62,95% CI 1.06-2.47), and taking action when they experienced CVD symptoms (30% vs. 23%,p = 0.03). Physician encouragement was cited as the reason for taking preventive action more often by black (59%,p = 0.002) and Hispanic (54%,p = 0.03) women than whites/others (43%). CONCLUSIONS: Continued initiatives to improve and translate knowledge into preventive action are needed, especially among less educated and Hispanic women who may activate others to reduce risk. PMID- 20575621 TI - Time to significant pain reduction following DETP application vs placebo for acute soft tissue injuries. AB - OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) provide fast and effective acute pain relief, but systemic administration has increased risk for some adverse reactions. The diclofenac epolamine 1.3% topical patch (DETP) is a topical NSAID with demonstrated safety and efficacy in treatment of acute pain from minor soft tissue injuries. Significant pain reduction has been observed in clinical trials within several hours following DETP application, suggesting rapid pain relief; however, this has not been extensively studied for topical NSAIDs in general. This retrospective post-hoc analysis examined time to onset of significant pain reduction after DETP application compared to a placebo patch for patients with mild-to-moderate acute ankle sprain, evaluating the primary efficacy endpoint from two nearly identical studies. RESEARCH DESIGN AND METHODS: Data from two double-blind, randomized, parallel-group, placebo-controlled studies (N = 274) of safety and efficacy of the DETP applied once daily for 7 days for acute ankle sprain were evaluated post-hoc using statistical modeling to estimate time to onset of significant pain reduction following DETP application. MAIN OUTCOME MEASURES: Pain on active movement on a 100 mm Visual Analog Scale (VAS) recorded in patient diaries; physician- and patient-assessed tolerability; and adverse events. RESULTS: DETP treatment resulted in significant pain reduction within approximately 3 hours compared to placebo. Within-treatment post hoc analysis based on a statistical model suggested significant pain reduction occurred as early as 1.27 hours for the DETP group. The study may have been limited by the retrospective nature of the analyses. In both studies, the DETP was well tolerated with few adverse events, limited primarily to application site skin reactions. CONCLUSION: The DETP is an effective treatment for acute minor soft tissue injury, providing pain relief as rapidly as 1.27 hours post treatment. Statistical modeling may be useful in estimating time to onset of pain relief for comparison of topical and oral NSAIDs. PMID- 20575622 TI - Drug repurposing for drug development in stroke. AB - The development of new treatments for acute stroke has been fraught with costly and spectacularly disappointing failures. Repurposing of drugs already known to be safe provides a lower risk alternative. Investigators are using drug repurposing, in which marketed drugs are exploited for their secondary activity, to pursue agents that have multiple mechanisms of action, including vascular protection. Protecting the ischemic vasculature is likely to promote neuronal recovery and have long-lasting benefits for patients with stroke. Currently, reperfusion with drugs or devices and acute aspirin therapy are used clinically to reduce disability due to ischemic stroke. In the future, drugs such as statins, angiotensin II receptor blockers, minocycline, and growth factors such as erythropoietin may be used. In fact, vascular protection with the angiotensin II receptor blocker candesartan has already been demonstrated in a clinical trial of acute ischemic stroke. PMID- 20575624 TI - Targeting the brain: neuroprotection and neurorestoration in ischemic stroke. AB - Many treatments for acute ischemic stroke are vessel and blood based, but brain based therapies also hold great promise. Acute neuroprotective therapies block the molecular elaboration of injury in hypoxic environments. Prehospital trials of magnesium sulfate are demonstrating the feasibility of delivering potentially brain-protective agents in the first minutes after stroke onset. Subacute neurorestoration therapies enhance neuroplasticity and brain reorganization after stroke. The greatest clinical experience with agents that can potentiate brain repair has been gained with choline precursors. Therapies that target the brain in patients with stroke will increasingly complement and enhance traditional vasotherapeutics. PMID- 20575623 TI - Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: minocycline. AB - Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned. PMID- 20575626 TI - Opioid harm reduction strategies: focus on expanded access to intranasal naloxone. PMID- 20575627 TI - Efflux pump contribution to multidrug resistance in clinical isolates of Pseudomonas aeruginosa. AB - STUDY OBJECTIVE: To determine if increased expression of efflux pumps, mutations in the genes encoding regulatory proteins for efflux pumps, or the combination is associated with multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. DESIGN: Microbiologic evaluation of prospectively collected Pseudomonas aeruginosa isolates. SETTING: University teaching hospital. ISOLATES: One hundred eight unique P. aeruginosa isolates-50 non-MDR and 58 MDR isolates-obtained from pulmonary or blood sources from patients admitted to the intensive care unit between January 1, 1999, and December 31, 2004. MEASUREMENTS AND MAIN RESULTS: Isolates were considered MDR if they were resistant to at least three of the following four drugs: ciprofloxacin, tobramycin, ceftazidime, or imipenem. Possible mutations in efflux regulatory genes mexR, nfxB, and mexZ were analyzed by using polymerase chain reaction amplification and DNA sequencing. Determination of the expression of outer membrane proteins OprM and OprJ was performed by using sodium dodecyl sulfate- polyacrylamide gel electrophoresis immunoblotting. Differences in regulatory gene mutations and outer membrane protein expression were compared between non-MDR and MDR isolates. Among the 108 P. aeruginosa isolates, the MDR isolates were more likely to overexpress OprM compared with non-MDR isolates (64% vs 2%, p<0.001). Mutations in mexR and mexZ were present in 64% and 26% of MDR strains, respectively, but were not associated with OprM overexpression or multidrug resistance. Expression of OprJ was not associated with MDR isolates (odds ratio [OR] 3.7, 95% confidence interval [CI] 0.7-18.5, p=0.11). Mutations in nfxB (12% of MDR strains) were also not associated with multidrug resistance (OR 3.5, 95% CI 0.7-17.8, p=0.13). Eight (100%) of 8 isolates with OprJ expression plus OprM overexpression, 12 (92%) of 13 isolates with combined mexR and mexZ mutations, 5 (100%) of 5 isolates with nfxB plus mexZ mutations, and 16 (100%) of 16 isolates with OprM overexpression plus mexZ mutations were MDR isolates. CONCLUSION: The presence of one regulatory gene mutation or simple expression of a single outer membrane protein was not linked to multidrug resistance. However, OprM overexpression and multiple efflux regulatory gene mutations or efflux protein expression were associated with MDR P. aeruginosa isolates. PMID- 20575628 TI - Impact of enhanced external counterpulsation on Canadian Cardiovascular Society angina class in patients with chronic stable angina: a meta-analysis. AB - STUDY OBJECTIVE: To evaluate the true magnitude of benefit from enhanced external counterpulsation (EECP) by determining the effect of EECP on Canadian Cardiovascular Society (CCS) angina class in patients with chronic stable angina. DESIGN: Meta-analysis of 13 prospective studies that evaluated patients with stable angina and reported adequate data on CCS angina class. PATIENTS: A total of 949 adult patients with stable angina who underwent EECP treatment. MEASUREMENTS AND MAIN RESULTS: A systematic literature search of studies published between 1950 and February 2009 was performed. Studies were included for meta-analysis if they were reported in the English language, included human subjects, had a prospective study design, and reported adequate data on CCS angina class. The EECP treatment consisted of 35 sessions-1 hour/day, 5 days/week, for 7 weeks. Improvement in angina class was reported as the weighted proportion of patients improving by at least one CCS class from before to after EECP treatment. Heterogeneity was assessed by performing subgroup analyses and using the Cochran Q statistic. Publication bias was assessed by inspection of funnel plots and the Egger bias statistic. Among the 13 studies incorporating 949 patients, angina class was reduced by at least one CCS score in 86% of the patients (95% confidence interval 82-90%, Q statistic p=0.008]. Inspection of funnel plots showed some asymmetry, but the Egger bias statistic showed no publication bias (p=0.97). CONCLUSION: The results of our meta-analysis call for further long-term studies to determine the place of EECP therapy in the management of chronic stable angina. Currently, EECP therapy should be considered for patients with stable angina who are refractory to or not suitable for invasive therapy and/or medical management. PMID- 20575629 TI - Factors associated with increased hospital utilization in patients with heart failure and preserved ejection fraction. AB - STUDY OBJECTIVE: To determine whether controlling systolic blood pressure (SBP), pulse pressure, and heart rate in the outpatient setting is associated with decreased hospital utilization in patients with heart failure and preserved ejection fraction (PEF). DESIGN: Retrospective medical record review. SETTING: University-affiliated medical center and outpatient clinics. PATIENTS: One hundred forty adults admitted between January 1, 2003, and October 31, 2005, for an exacerbation of heart failure with PEF and followed for 2 years after their index admission. MEASUREMENTS AND MAIN RESULTS: Outpatient SBP, pulse pressure, and heart rate, and the percentage of clinic visits for which patients had each vital sign at a certain level were used for correlations and comparisons. These vital signs and percentages of clinic visits were varied until maximum significant differences were observed in total hospital utilization for each parameter. These values were then analyzed for differences based on age, race ethnicity, and sex. When comparing patients whose vital signs were in control for at least 80% of clinic visits versus those whose were in control for less than 80% of clinic visits, significantly lower hospital utilization was associated with clinic SBP less than 140 mm Hg (median hospital utilization 3 vs 5 visits, p=0.0252), pulse pressure less than 65 mm Hg (3 vs 5 visits, p=0.0113), and heart rate of 55-70 beats/minute (2 vs 4 visits, p=0.0311). Among the 140 patients, 78 (56%) were Caucasian, 48 (34%) were Hispanic, and 14 (10%) were African-American. The African-American patients were significantly younger (p=0.0218) and had significantly poorer SBP control (< 140 mm Hg for >/= 80% of clinic visits: 14.3% vs 43.8%, p=0.0446) and higher hospital utilization (> 4 visits: 78.6% vs 43.8%, p=0.0218) than the Hispanic patients, despite similar percentages of missed clinic appointments (25% for each group). CONCLUSION: Controlling SBP at less than 140 mm Hg, pulse pressure at less than 65 mm Hg, and heart rate at 55-70 beats/minute for at least 80% of clinic visits were factors associated with decreased hospital utilization. African-American patients with heart failure and PEF were younger, had more poorly controlled SBP, and had higher hospital utilization despite similar percentage of missed clinic visits as their Hispanic counterparts. PMID- 20575630 TI - Aminoglycoside pharmacokinetic parameters in neurocritical care patients undergoing induced hypothermia. AB - STUDY OBJECTIVE: To determine the effects of mild-to-moderate induced hypothermia a neuroprotectant and/or therapeutic strategy for the management of intracranial hypertension in neurologically injured patients-on the pharmacokinetics of aminoglycoside therapy. DESIGN: Pharmacokinetic analysis. SETTING: Critical care unit at a university-affiliated hospital. PATIENTS: Three patients, aged 22, 24, and 47 years, who received tobramycin and had documented tobramycin levels while undergoing induced hypothermia for more than 24 hours for intracranial hypertension. MEASUREMENTS AND MAIN RESULTS: For each of the three patients, predicted pharmacokinetic parameters (volume of distribution, first-order elimination rate constant, half-life, and renal drug clearance) based on population data were compared with their actual pharmacokinetic parameters that were calculated based on observed tobramycin serum levels. All three patients had a normal creatinine clearance, estimated according to established methods. When pharmacokinetic parameters were calculated after the first tobramycin dose using a one-compartment method, all patients had a slower first-order elimination rate and a larger volume of distribution compared with predicted population estimates. CONCLUSION: These findings suggest that induced hypothermia may result in impaired elimination of aminoglycosides. Caution should be exercised when attempting to use predicted pharmacokinetic parameters to dose aminoglycosides in this patient population, and first-dose pharmacokinetics should be considered to optimize the dose and dosing interval early in the course of therapy. Further investigation of this phenomenon with greater numbers of patients are needed to confirm these findings and to determine optimal dosing strategies of aminoglycosides in patients undergoing induced hypothermia. PMID- 20575631 TI - Drug interaction between itraconazole and bortezomib: exacerbation of peripheral neuropathy and thrombocytopenia induced by bortezomib. AB - STUDY OBJECTIVE: To investigate whether a drug interaction exists between bortezomib and the cytochrome P450 (CYP) 3A4 inhibitor itraconazole and/or the CYP2C19 inhibitor lansoprazole that results in increased severity of bortezomib induced peripheral neuropathy and thrombocytopenia. DESIGN: Retrospective medical record review. SETTING: Hematology-oncology ward of a university-affiliated hospital in Japan. PATIENTS: Six adults with relapsed multiple myeloma who received intravenous bortezomib plus oral dexamethasone as the first course of a 21-day cycle between July 2007 and December 2008. Four of the six patients were treated concomitantly with itraconazole or lansoprazole: two with itraconazole, one with lansoprazole, and one with both itraconazole and lansoprazole. MEASUREMENTS AND MAIN RESULTS: Using the National Cancer Institute's Common Terminology Criteria for Adverse Events, we identified the presence and graded the severity of peripheral neuropathy and thrombocytopenia before and during each patient's first 21-day course of bortezomib plus dexamethasone therapy. All three patients who received itraconazole experienced new or worsening peripheral neuropathy; they also experienced grade 4 thrombocytopenia. The patient who received lansoprazole alone, as well as the two patients who did not receive itraconazole or lansoprazole, had no changes in either adverse effect. We also evaluated the relationship between peripheral neuropathy and bortezomib plus dexamethasone therapy by using the Naranjo adverse drug reaction probability scale, and a probable relationship was found. We further assessed whether a drug interaction between bortezomib and itraconazole and/or lansoprazole had occurred involving the CYP3A4 and/or the CYP2C19 pathways, respectively-resulting in increased severity of the bortezomib-induced peripheral neuropathy and thrombocytopenia-by using the Horn drug interaction probability scale. We found that the occurrence of this drug interaction was strongly supported. CONCLUSIONS: Itraconazole appears to exacerbate peripheral neuropathy and thrombocytopenia induced by bortezomib; however, the mechanism of this drug interaction is unknown. Clinicians should closely monitor for bortezomib-induced adverse effects when itraconazole, or any other potent CYP3A4 inhibitor, is administered concomitantly with bortezomib. PMID- 20575632 TI - Treatment options for chronic refractory idiopathic thrombocytopenic purpura in adults: focus on romiplostim and eltrombopag. AB - Idiopathic thrombocytopenic purpura (ITP) is a platelet disorder that affects approximately 1 in 10,000 people. In adults, the rate of spontaneous remission is only 5%, and generally, it is a chronic disease persisting for more than 6 months. Chronic refractory ITP may be defined as the failure of any modality to keep the platelet count above 20 x 10(3)/mm(3) for an appreciable time without unacceptable toxicity. Many pharmacologic treatments have been used to manage chronic refractory ITP by attempting to increase platelet counts by decreasing the rate of destruction of these cells. They include, but are not limited to, azathioprine, danazol, dapsone, combination chemotherapy, cyclosporine, and rituximab. However, these therapies offer modest response rates and can cause adverse events that necessitate drug discontinuation. The recent United States Food and Drug Administration approval of the thrombopoietin mimetics, romiplostim and eltrombopag, has provided clinicians with a novel approach for treating chronic refractory ITP. By stimulating platelet production, these drugs offer patients with this disease an alternative to the other agents. The preapproval phase III study with subcutaneous romiplostim showed significantly higher overall response rates versus placebo in both splenectomized and nonsplenectomized patients (83% for romiplostim vs 7% for placebo, p<0.0001). Twenty-five percent of patients receiving romiplostim achieved a platelet count greater than 50 x 10(3)/mm(3) after 1 week, and 50% achieved this platelet count within 2-3 weeks. The preapproval phase III study with oral eltrombopag demonstrated that 70% of patients receiving 50 mg/day and 81% of patients receiving 75 mg/day achieved a platelet count of at least 50 x 10(3)/mm(3) by day 43 (p<0.001 vs placebo for both 50 and 75 mg). Forty-four percent and 62% of patients achieved a platelet count of at least 50 x 10(3)/mm(3) by day 8 with eltrombopag 50 and 75 mg/day, respectively. When deciding which of these agents to prescribe, considerations include oral versus injectable dosage form, adverse-event profiles, and patient adherence with both taking the drug and keeping clinic appointments for monitoring of platelet counts. Several studies are under way to evaluate these drugs in chronic refractory ITP as well as other disease states. Long-term data will also be needed to assess the safety and efficacy of these agents. PMID- 20575633 TI - Drug-induced QT-interval prolongation: considerations for clinicians. AB - Drug-induced proarrhythmia is a frequently encountered clinical problem and a leading cause for withdrawal or relabeling of prescription drugs. Suppression of the rapid component of the delayed rectifier potassium current, I(Kr), represents the principal pharmacodynamic mechanism leading to heterogeneous prolongation of the ventricular action potential and prolongation of the QT interval clinically. However, the risk of proarrhythmia by QT-interval-prolonging drugs is variable and critically dependent on several factors leading to multiple reductions in the cardiac repolarization reserve. As antiarrhythmic drugs that prolong the QT interval are usually aggressively managed with continuous electrocardiogram monitoring and screening for drug interactions when administered to patients who have a high risk of sudden cardiac death, their risk of mortality is not increased. However, noncardiovascular QT-interval-prolonging drugs, which often produce less QT-interval prolongation compared with antiarrhythmic drugs, are found to be associated with increased rates of death in patients who have a markedly lower de novo risk of sudden cardiac death. Thus, it is important for clinicians, particularly pharmacists, to be cognizant of the levels of risk associated with varying degrees of QT-interval prolongation caused by drugs so that they can develop strategies to either prevent or reduce the risk of proarrhythmias. PMID- 20575634 TI - Methylene blue for the treatment of septic shock. AB - Septic shock is a major cause of morbidity and mortality in the intensive care unit, and effective therapies are limited. Methylene blue is a selective inhibitor of guanylate cyclase, a second messenger involved in nitric oxide mediated vasodilation. The use of methylene blue in the treatment of septic shock has been repeatedly evaluated over the past 20 years, but data remain scarce. To evaluate the safety and efficacy of methylene blue for the treatment of septic shock, we conducted a literature search of the EMBASE (1974-June 2009), MEDLINE (1966-June 2009), and International Pharmaceutical Abstracts (1970-June 2009) databases. All available studies published in English were reviewed. Observational studies with methylene blue have demonstrated beneficial effects on hemodynamic parameters and oxygen delivery, but use of methylene blue may be limited by adverse pulmonary effects. Methylene blue administration is associated with increases in mean arterial pressure while reducing catecholamine requirements in patients experiencing septic shock; however, its effects on morbidity and mortality remain unknown. Well-designed, prospective evaluations are needed to define the role of methylene blue as treatment of septic shock. PMID- 20575635 TI - Bone loss and fracture risk associated with thiazolidinedione therapy. AB - The increasing use of thiazolidinediones for the treatment of type 2 diabetes mellitus, coupled with the potential for fractures in the aging population, poses a significant concern for health care providers. This concern is based on many reports of postapproval adverse musculoskeletal effects, particularly bone changes and fractures. To better understand the effects of thiazolidinediones on bone health, we conducted a PubMed search of articles published from January 1966 June 2009. We reviewed the hypothesized mechanisms for thiazolidinedione-induced adverse effects on bone, studies that evaluated thiazolidinedione use and fracture risk, potential treatment options for fracture minimization, and future directions for research. Thiazolidinedione-induced bone changes may stem from the ability of these drugs to reduce the activity of osteoblasts without an appreciable effect on osteoclasts, shifting the balance of bone homeostasis to favor bone loss. Clinical data suggest that treating patients who have type 2 diabetes with thiazolidinediones has detrimental effects on bone health, as measured by reduced bone mineral density and increased fracture rates, notably distal extremity fractures in female patients. Thiazolidinediones are selective peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists; thus, continued pursuit of PPAR system selectivity and investigation of other PPAR agonists are crucial to understanding and avoiding these detrimental effects. Clinicians, particularly pharmacists, must take an active role in educating colleagues on the importance of screening thiazolidinedione-treated patients for fracture risk, counseling patients on adequate calcium and vitamin D intake and fall prevention, and appropriately selecting therapy for secondary prevention of fracture. PMID- 20575636 TI - Inhaled epoprostenol for the treatment of pulmonary arterial hypertension in critically ill adults. AB - Pulmonary arterial hypertension (PAH) is a progressive disease without a cure. The primary treatment goal for patients with this disease is improving pulmonary blood flow through vasodilation of the pulmonary arteries. Several drugs are available that ameliorate walk distance and hemodynamics, but their maximum tolerated doses are limited in critically ill patients with PAH because of systemic vasodilation resulting in hypotension. The ideal vasodilator would be cost-effective, safe, and selective to the pulmonary vasculature; no such agent currently exists. Inhaled nitric oxide selectively reduces pulmonary pressures without systemic hypotension. However, it is expensive, potentially toxic, and requires complex technology for monitoring and administration. Inhaled epoprostenol may be an alternative therapy to minimize systemic hypotension, which often accompanies rapid intravenous titration. To evaluate the safety and efficacy of inhaled epoprostenol in critically ill patients with PAH, we conducted a literature search by using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases (1966-August 2009) for relevant studies. Case reports and in vitro studies were excluded. Overall, 11 studies met the inclusion criteria. The PAH population included patients requiring cardiac surgery, lung or heart transplantation, or nonspecific intensive care. All trials showed that inhaled epoprostenol significantly decreased pulmonary pressures without lowering systemic blood pressure. The duration of therapy in most studies was 10-15 minutes, with one study evaluating its effects up to an average of 45.6 hours. Pulmonary pressures returned to baseline soon after drug discontinuation. Minimal adverse events were reported. Thus, inhaled epoprostenol in various subgroups of critically ill patients was effective in reducing pulmonary pressures. However, the significance of these effects on improving clinical outcomes remains unknown. Further studies are needed to determine the role of inhaled epoprostenol in critically ill patients with PAH. PMID- 20575637 TI - Evaluation of morbidity and mortality data related to cardiovascular calcification from calcium-containing phosphate binder use in patients undergoing hemodialysis. AB - Cardiovascular disease is the leading cause of death among patients with stage 5 chronic kidney disease. Several mechanisms are thought to contribute to vascular calcification and subsequent cardiovascular disease in patients who require hemodialysis. One of these mechanisms is the use of calcium-containing phosphate binders to treat hyperphosphatemia. Although most phosphate binding occurs in the gastrointestinal tract, some calcium is inevitably absorbed and has the potential to perpetuate the calcium-phosphorus product and the development of vascular and soft tissue calcification. Some phosphate binders such as sevelamer hydrochloride do not contain calcium and therefore may not carry the same risks. We examined the cardiovascular calcification effect and morbidity and mortality data with calcium-containing phosphate binders compared with sevelamer hydrochloride when given to patients with stage 5 chronic kidney disease for the treatment of hyperphosphatemia. A literature search using the MEDLINE and PubMed databases identified relevant articles from 1989-2009; nine studies compared vascular calcification between a calcium-containing phosphate binder and sevelamer hydrochloride. Three mortality studies were also identified. Seven of the nine studies reported a statistically significant increase in vascular calcification in patients taking calcium-containing phosphate binders as measured by coronary artery calcification scores and aortic calcification scores. In two trials, lower mortality rates were observed in the patients receiving sevelamer hydrochloride compared with calcium-containing phosphate binders. No significant difference in the mortality rate was observed in the third trial. Based on the current literature, it appears that calcium-containing phosphate binders promote the progression of vascular calcification to a greater extent than does sevelamer hydrochloride. In addition, some evidence suggests that sevelamer hydrochloride may reduce all-cause mortality rates in patients undergoing hemodialysis, particularly those aged 65 years or older. Thus, although sevelamer hydrochloride appears to be the more appropriate choice of phosphate binder for patients undergoing hemodialysis in whom cardiovascular calcification is a concern, more clinical trials are needed to further guide practitioners on the selection of phosphate binders. PMID- 20575638 TI - Pharmacologic prophylaxis of postoperative atrial fibrillation in patients undergoing cardiac surgery: beyond beta-blockers. AB - Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery that increases patient morbidity, length of stay, and hospital costs. A substantial body of evidence exists evaluating various pharmacologic and nonpharmacologic methods to decrease the occurrence of POAF in an effort to decrease its burden on the health care system. Evidence-based guidelines support the use of beta-blockers as standard prophylaxis of POAF in patients undergoing cardiac surgery. Traditional prophylactic therapy for POAF targets the sympathetic nervous system, refractory period, and atrial conduction. However, associations between the development of POAF and the inflammatory process, oxidative stress, and atrial remodeling have prompted the investigation of novel therapies targeting these processes. To evaluate the role of pharmacologic strategies beyond beta-blockers in the prevention of POAF, we conducted a search of the PubMed database to identify studies published from 1950-February 2009. Emphasis was placed on how these therapies could be used in patients intolerant to beta-blockers or as additive therapy in high-risk patients. We found that sufficient evidence exists to recommend the use of amiodarone, sotalol, and possibly magnesium as monotherapy in patients unable to take beta-blockers or as add-on therapy for the prevention of POAF. Currently, available evidence does not support the use of propafenone, procainamide, digoxin, thiazolidinediones, triiodothyronine, or calcium channel blockers in the prevention of POAF. Preliminary evidence suggests that dofetilide, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), nonsteroidal antiinflammatory drugs, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, and sodium nitroprusside may be effective in preventing POAF. Additional large-scale, adequately powered clinical studies are needed to determine the benefit of these agents before they can be considered for routine use. PMID- 20575639 TI - CCL4/MIP-1beta levels in tear fluid and serum of patients with cystic fibrosis. AB - Cystic fibrosis (CF) is an autosomal recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to assess the potential role of MIP-1beta in the pathogenesis of dry eye syndrome in patients with CF. We assayed MIP-1beta levels in tear fluid and serum of 28 patients with CF and 27 controls by ELISA. The ophthalmic examinations including the tests for dry eye were used to study the ocular surface. The tear levels of MIP-1beta in the CF patients were significantly higher than those in the controls. Dry eye syndrome was observed in 10 (36%) CF patients. The tear fluid levels of MIP-1beta were significantly raised in CF patients with dry eye syndrome compared with CF patients without dry eye symptoms. Our results suggest a crucial role of CCL4/MIP-1beta in the development of dry eye syndrome in CF patients and immunopathogenesis of ocular surface changes in this disease. Clarification of the role of CCL4/MIP-1beta in the pathogenesis of ocular findings in CF patients will be useful in establishing immunotherapeutic strategies for this disease. PMID- 20575641 TI - Seroepidemiology of nine zoonoses in Viljujsk, Republic of Sakha (Northeastern Siberia, Russian Federation). AB - A seroepidemiology survey of nine zoonoses was carried out in 2007 on 90 healthy adult volunteers in Viljujsk, a northern city in the Republic of Sakha (Eastern Siberia). The seroprevalence of Lyme borreliosis was 3.3% by immunofluorescence. None of the subjects displayed a positive enzyme-linked immunosorbent assay/Western blot result for alveolar or cystic echinococcosis. The seroprevalence of toxocariasis by Western blot was 4.4%, and 8.9% of the subjects had anti-Toxoplasma IgG. By enzyme-linked immunosorbent assay, the seroprevalence of trichinellosis was 4.4%. Three subjects were simultaneously positive for tick borne encephalitis and West Nile infection, so no clear diagnostic conclusion could be reached for these flavivirus diseases. Interestingly, Crimea-Congo hemorrhagic fever had an 11.1% seroprevalence rate, indicating that Viljujsk is the most northern focus of this infection. Additionally, this finding suggests a potential involvement of Crimea-Congo hemorrhagic fever agent, or of another member of the Bunyaviridae family, in the genesis of the so-called Viljujsk encephalomyelitis. PMID- 20575642 TI - The utility of animal surveillance in the detection of West Nile virus activity in Puerto Rico, 2007. AB - After the isolation of West Nile virus (WNV) from humans, mosquitoes, and chickens in 2007, an analysis of animal surveillance involving multiple species (horses, monkeys, sheep, dogs, and birds) used to track WNV transmission from 2006 to 2008 was performed. During this period 13.4% of all the animal samples collected were seropositive by blocking ELISA for WNV. The most complete island wide sampling was obtained from horses of which 22% were serologically positive and 96% were confirmed as WNV infections by plaque-reduction neutralization test. Our conclusion from this 3-year study is that animal surveillance is an early indicator of WNV activity before the identification of human cases. Additionally, the results indicated that horses have a greater geographical range and should be continued to be used as sentinels for passive surveillance in the tropics. PMID- 20575640 TI - Human stem/progenitor cells from bone marrow enhance glial differentiation of rat neural stem cells: a role for transforming growth factor beta and Notch signaling. AB - Multipotent stem/progenitor cells from bone marrow stroma (mesenchymal stromal cells or MSCs) were previously shown to enhance proliferation and differentiation of neural stem cells (NSCs) in vivo, but the molecular basis of the effect was not defined. Here coculturing human MSCs (hMSCs) with rat NSCs (rNSCs) was found to stimulate astrocyte and oligodendrocyte differentiation of the rNSCs. To survey the signaling pathways involved, RNA from the cocultures was analyzed by species-specific microarrays. In the hMSCs, there was an upregulation of transcripts for several secreted factors linked to differentiation: bone morphogenetic protein 1 (BMP1), hepatocyte growth factor (HGF), and transforming growth factor isoforms (TGFbeta1 and TGFbeta3). In both the hMSCs and the rNSCs, there was an upregulation of transcripts for Notch signaling. The role of TGFbeta1 was verified by the demonstration that hMSCs in coculture increased secretion of TGFbeta1, the rNSCs expressed the receptor, and an inhibitor of TGFbeta signaling blocked differentiation. The role of Notch signaling was verified by the demonstration that in the cocultures hMSCs expressed a Notch ligand at sites of cell contact with rNSCs, and the rNSCs expressed the receptor, Notch 1. Increased Notch signaling in both cell types was then demonstrated by assays of transcript expression and by a reporter construct for downstream targets of Notch signaling. The results demonstrated that glial differentiation of the rNSCs in the cocultures was driven by increased secretion of soluble factors such as TGFbeta1 by the hMSCs and probably through increased cell contact signaling between the hMSCs and rNSCs through the Notch pathway. PMID- 20575643 TI - Phlebovirus meningoencephalis complicated by Pseudomonas aeruginosa pneumonia: a case report. AB - In June 2004 an 8-year-old boy was admitted to a hospital in Thessaloniki, Greece, because of high fever, tachypnea, hypotonia, diarrhea, and tonoclonic convulsions. Phlebovirus infection was diagnosed by IgG seroconversion to Toscana virus. As IgM antibodies were not detected, it is suggested that this was an acute infection caused by a phlebovirus virus distinct from Toscana virus. Complication by a hospital-acquired Pseudomonas aeruginosa pneumonia resulted in 2 months of hospitalization. Slight ataxia was still present on discharge. PMID- 20575644 TI - Prevalence of Dirofilaria immitis infection in dogs from Celestun, Mexico, using polymerase chain reaction test. AB - The aim of this study was to determine the prevalence of Dirofilaria immitis in dogs and to analyze risk factors associated with infection at Celestun, a coastal locality in southeast Mexico. Blood samples were collected from 279 asymptomatic individuals between August 2007 and March 2008 and analyzed by polymerase chain reaction technique. The association between D. immitis infection and sex, age group, and distance of residence from a wetland of dogs was statistically analyzed. Prevalence of D. immitis infection was of 59.8%. Age of individuals (>2 years) was a risk factor for infection with D. immitis (odds ratio 2.49, confidence interval 1.47-4.23, p=0.001). In conclusion, Celestun can be considered a focus of D. immitis infection with high levels of transmission among the local dog population, as confirmed by the high prevalence reported and the association of age (dogs >2 years) as a risk associated with infection. PMID- 20575645 TI - Francisella-like endosymbiont in Dermacentor reticulatus collected in Portugal. AB - In Portugal, recent studies have confirmed the presence of Francisella tularensis in Dermacentor reticulatus. Bacterial endosymbionts with significant homology to F. tularensis have been described in several species of ticks. In this work we identified Francisella-like endosymbionts in D. reticulatus ticks (39%), confirming the presence of these bacteria in Portugal. This finding should be considered in future studies using molecular approaches to detect Francisella prevalence in ticks and environmental samples. PMID- 20575646 TI - Molecular detection of Leishmania infection due to Leishmania major and Leishmania turanica in the vectors and reservoir host in Iran. AB - An epidemiological study was carried out on the vectors and reservoirs of cutaneous leishmaniasis in rural areas of Damghan district, Semnan province, central Iran, during 2008-2009. Totally, 6110 sand flies were collected using sticky papers and were subjected to molecular methods for detection of Leishmania parasite. Phlebotomus papatasi Scopoli was the common species in outdoor and indoor resting places. Polymerase chain reaction technique showed that 24 out of 218 P. papatasi (11%) and 4 out of 62 Phlebotomus caucasicus Marzinovskyi (6.5%) were positive for parasites Leishmania major Yakimoff and Schokhor. Twenty-one rodent reservoir hosts captured using Sherman traps were identified as Rhombomys opimus Lichtenstein (95%) and Meriones libycus Lichtenstein (5%). Microscopic investigation on blood smear of the animals for amastigote parasites revealed 8 (40%) rodents infected with R. opimus. L. major infection in these animals was then confirmed by polymerase chain reaction against internal transcribed spacer ribosomal DNA (rDNA) loci of the parasite followed by restriction fragment length polymorphism. Further, sequence analysis of 297 bp of ITS1-rDNA loci revealed the presence of L. major and Leishmania turanica in P. papatasi, and L. major in R. opimus. This is the first molecular report of L. major infection in both vectors (P. papatasi and P. caucasicus) and reservoir host (R. opimus) in this region. The results indicated that P. papatas was the primary vector of the disease and circulating the parasite between human and reservoirs, and P. caucasicus could be considered as a secondary vector. Further, our study showed that R. opimus is the most important host reservoir for maintenance of the parasite source in the area. PMID- 20575647 TI - First molecular evidence of potentially zoonotic Babesia microti and Babesia sp. EU1 in Ixodes ricinus ticks in Belgium. AB - We report the first molecular evidence of the presence of Babesia sp. EU1 and Babesia microti in Ixodes ricinus ticks in Belgium. A 1-year national survey collected 1005 ticks from cats and dogs. A polymerase chain reaction technique amplifying a part of the 18S rRNA gene detected Babesia spp. in 11 out of 841 selected and validated tick extracts. Subsequent sequencing identified Ba. microti (n=3) and Babesia sp. EU1 (n=6). This study has demonstrated a low infection rate (1.31% with 95% CI: 0.65-2.33) of Babesia spp. carriage in I. ricinus ticks in Belgium but, for the first time, reports two potentially zoonotic species belonging to this genus. Coinfection with Ba. microti and Borrelia burgdorferi sensu stricto also was demonstrated. In addition, this study clearly demonstrates that inhibitors of polymerase chain reaction amplification are present in engorged ticks. PMID- 20575648 TI - Prevalence of Trypanosoma cruzi in dogs (Canis familiaris) and triatomines during 2008 in a sanitary region of the State of Mexico, Mexico. AB - American trypanosomiasis is a public health problem in Latin America and southern parts of the United States. Infection in triatomines (vector) and domestic dogs (reservoir host) is a good indicator of Trypanosoma cruzi circulation and human risk of infection. The State of Mexico, Mexico, has been considered free of T. cruzi, and no detailed epidemiologic study has been conducted to assess the intricacies of the transmission cycle of the parasite in the region. Such studies would enhance our understanding of the epidemiology of T. cruzi infection in this geographic region and provide regional sanitary authorities with stronger fundamental knowledge for making decisions and allocating funds for Chagas disease control programs in the State of Mexico. The objective of this study was to determine the prevalence of T. cruzi infection in dogs (seroprevalence) and triatomines (fecal parasites) in a previously identified, discrete endemic region of parasite circulation and to widen our studies in the Tejupilco Sanitary Region located in the southern part of the State of Mexico. Dog blood samples (n=102) were analyzed for the presence of anti-T. cruzi antibodies by two assays, namely indirect hemagglutination assay and enzyme-linked immunosorbent assay. Triatomines (n=88) were collected and fecal aliquots were analyzed for the presence of parasites by light microscopy. Average seroprevalence in dogs in the Tejupilco Sanitary region was 24.5%, and the overall triatomine infection rate was 34.01%. Triatoma pallidipennis was the only triatomine species found in this region. Our data demonstrate that T. cruzi is actively circulating in the Tejupilco Sanitary Region and emphasize the requirement for epidemiologic surveillance programs throughout the putative endemic areas of the State of Mexico. PMID- 20575649 TI - Contacts related to mental illness and substance abuse in primary health care: a cross-sectional study comparing patients' use of daytime versus out-of-hours primary care in Norway. AB - OBJECTIVE: To investigate prevalence, diagnostic patterns, and parallel use of daytime versus out-of-hours primary health care in a defined population (n = 23,607) in relation to mental illness including substance misuse. DESIGN: Cross sectional observational study. SETTING: A Norwegian rural general practice cooperative providing out-of-hours care (i.e. casualty clinic) and regular general practitioners' daytime practices (i.e. rGP surgeries) in the same catchment area. SUBJECTS: Patients seeking medical care during daytime and out-of hours in 2006. MAIN OUTCOME MEASURES: Patients' diagnoses, age, gender, time of contact, and parallel use of the two services. RESULTS: Diagnoses related to mental illness were given in 2.2% (n = 265) of encounters at the casualty clinic and in 8.9% (n = 5799) of encounters at rGP surgeries. Proportions of diagnoses related to suicidal behaviour, substance misuse, or psychosis were twice as large at the casualty clinic than at rGP surgeries. More visits to the casualty clinic occurred in months with fewer visits to rGP surgeries. Most patients with a diagnosis related to mental illness at the casualty clinic had been in contact with their rGP during the study period. CONCLUSION: Psychiatric illness and substance misuse have lower presentation rates at casualty clinics than at rGP surgeries. The distribution of psychiatric diagnoses differs between the services, and more serious mental illness is presented out-of-hours. The casualty clinic seems to be an important complement to other medical services for some patients with recognized mental problems. PMID- 20575650 TI - Kleptomania: clinical characteristics and relationship to substance use disorders. AB - BACKGROUND: Although categorized as an impulse control disorder, kleptomania has many features in common with substance use disorders. OBJECTIVES: This paper sought to examine the mounting evidence supporting the phenomenological, clinical, epidemiological, and biological links between kleptomania and substance addictions. METHODS: A review of the literature examining family history, genetics, comorbid psychiatric conditions, neuroimaging, and phenomenology was utilized to examine the relationship of kleptomania to substance addiction. RESULTS: Kleptomania and substance addiction share common core qualities, including similar treatment successes, as well as etiologic and phenomenological similarities. CONCLUSIONS: Future research investigating the relationship between kleptomania and substance use disorders holds significant promise in advancing prevention and treatment strategies for addiction in general. SCIENTIFIC SIGNIFICANCE: Research investigating kleptomania (and other behavioral addictions) and its relationship to substance addiction holds significant promise in advancing prevention and treatment strategies for addiction in general. PMID- 20575651 TI - Pathological gambling and substance use disorders. AB - BACKGROUND: Pathological gambling (CPG) has been considered as a behavioral addiction having similarities with substance use disorders (SUDs). OBJECTIVES AND METHODS: Current conceptualizations of addiction, as well as experimental studies of PG and SUDs, are reviewed in order to provide a perspective on tbe areas of convergence between addictive behaviors in PG and SUDs. RESULTS: Shared features exist in diagnostic, clinical, physiological, and behavioral domains. CONCLUSIONS AND SCIELLTIFIC SIGNIFICANCE: Similarities between PG and SUDs have important implicatiol1s for categorizing, assessing, preventing and treating both PO and SUDs. PMID- 20575652 TI - Pathologic skin picking. AB - BACKGROUND: Pathologic skin picking (PSP) is characterized by the repetitive and compulsive picking of skin which results in tissue damage. OBJECTIVES: This article sought to examine the evidence supporting the phenomenological, and biological links between PSP and substance use disorders. METHODS: A review of the literature examining clinical presentation, comorbid psychiatric conditions, and treatment studies was used to examine the relationship of PSP and substance use disorders. RESULTS: Prevalence rates of PSP range from 1.4-5.4% in the general population, with a much higher preponderance in females and in psychiatric patients. Significant medical complications are common, including scarring and infection. Although some pharmacologic agents (selective serotonin reuptake inhibitors, opioid antagonists, and glutamatergic agents) and non pharmacologic treatments (habit-reversal therapy, Internet-based treatments, and acceptance-enhanced behavior therapy) have shown early promise in treating this often disabling disorder, evidence-based treatment options are still limited. CONCLUSIONS: PSP shares several clinical similarities with substance use disorders including the failure to stop the behavior despite knowledge of the consequences and an associated pleasurable quality while engaging in the activity. SCIENTIFIC SIGNIFICANCE: The consideration of some other impulse control disorders (e.g., pathological gambling) as addictions has helped advance treatment strategies. Conceptualizing PSP as an addiction, in some individuals, may lead to more effective treatment approaches. PMID- 20575653 TI - N-terminal pro brain natriuretic peptide reflects long-term complications in type 1 diabetes. AB - PURPOSE: To evaluate N-terminal pro brain natriuretic peptide (NT-proBNP) as a marker of long-term micro- and macrovascular complications in type 1 diabetes. METHODS: This was a cross-sectional study of 208 long-term surviving type 1 diabetic patients from a population-based cohort from Fyn County, Denmark. In a clinical examination in 2007-2008, NT-proBNP was measured and related to proliferative diabetic retinopathy (PDR), nephropathy, neuropathy and macrovascular disease. RESULTS: Median age and duration of diabetes was 58.7 and 43 years, respectively. Median NT-proBNP concentration was 78 pg/ml (10th-90th percentile 25-653 pg/ml). The NT-proBNP level (89 vs. 71 pg/ml, p = 0.02) was higher in women. In univariate analyses, NT-proBNP was associated with age, duration of diabetes, diastolic blood pressure (inversely), nephropathy, neuropathy and macrovascular disease. For instance, median NT-proBNP concentrations were 70, 91 and 486 pg/ml for patients with normo-, micro- and macroalbuminuria, respectively (p < 0.01). When adjusted for age, sex, duration of diabetes, high sensitivity CRP, HbA(1c), diastolic blood pressure and smoking, higher NT-proBNP concentrations (4th vs. 1st quartile) were related to nephropathy (odds ratio [OR] 5.03; 95% confidence interval [CI] 1.77-14.25), neuropathy (OR 4.08; 95% CI 1.52-10.97) and macrovascular disease (OR 5.84; 95% CI 1.65-20.74). There was no association with PDR. CONCLUSIONS: NT-proBNP has traditionally been described as a marker of heart failure and left ventricular dysfunction. In this study of long-term surviving type 1 diabetic patients, we found NT-proBNP associated with nephropathy, neuropathy and macrovascular disease. If confirmed by prospective studies, NT-proBNP might be a useful prognostic marker of diabetes-related complications. PMID- 20575654 TI - Transdermal estradiol and oral or vaginal natural progesterone: bleeding patterns. AB - OBJECTIVE: To evaluate the effects on bleeding pattern of two different doses of natural progesterone (NP) administered per os or per vagina in association with transdermal estradiol in a continuous, sequential estrogen-progestin therapy. METHODS: A prospective, randomized trial was conducted on 100 patients randomized into four groups. Each group received transdermal 17beta-estradiol treatment at the dose of 50 microg/day. Groups A and B received NP per os at the dose of 100 mg/day and 200 mg/day, respectively. Groups C and D received NP per vagina at the dose of 100 mg/day and 200 mg/day, respectively. RESULTS: After 12 cycles of treatment, no significant differences were observed in endometrial thickness between groups, suggesting that all treatments are effective in balancing the effects of estradiol on endometrium. Regarding bleeding control, patients in Groups C and D showed a higher number of episodes of regular bleeding than patients in Groups A and B and fewer episodes of spotting. The better control of bleeding was associated with a higher treatment compliance in patients who received vaginal NP, with a larger percentage of women completing the study. CONCLUSION: Transdermal estrogen replacement therapy combined with 100 mg of micronized NP administered per vagina from the 14th day to the 25th day of each 28-day cycle leads to good cycle control and provides excellent patient satisfaction without serious side-effects. This therapy could be a treatment of first choice in early postmenopausal patients. PMID- 20575655 TI - Premature ovarian failure with FMR1 premutation, X chromosome mosaicism and blood lymphocyte microchimerism. AB - Genetic causes of premature ovarian failure (POF) comprise less than one-third of all cases, among them X chromosome abnormalities, mutations and polymorphisms in some genes. The frequency of X-chromosome mosaicism in women with sporadic POF has been found to range between 3 and 10%, whereas the prevalence of POF in carriers of the FMR1 premutation is estimated to range between 13 and 25%. We report two successful pregnancy outcomes after in vitro fertilization-embryo transfer with donated oocytes in a woman with severe POF of a complex genetic origin. Chromosome analysis, fluorescence in situ hybridization on cultured peripheral blood lymphocytes and buccal mucosal cells, and molecular genetic studies, using autosomal, Y-chromosomal polymorphic microsatellite or short tandem repeat markers and CGG repeats in the FMR1 gene, were performed. FMR1 premutation, sex chromosome mosaicism and blood lymphocyte microchimerism were found. Assisted reproduction techniques can be safely used in POF women after a thorough clinical evaluation and genetic counselling. PMID- 20575656 TI - Luciferase labeling for multipotent stromal cell tracking in spinal fusion versus ectopic bone tissue engineering in mice and rats. AB - Tissue engineering of bone, by combining multipotent stromal cells (MSCs) with osteoconductive scaffolds, has not yet yielded any clinically useful applications so far. The fate and contribution of the seeded cells are not sufficiently clarified, especially at clinically relevant locations. Therefore, we investigated cell proliferation around the spine and at ectopic sites using noninvasive in vivo bioluminescence imaging (BLI) in relation to new bone formation. Goat MSCs were lentivirally transduced to express luciferase. After showing both correlation between MSC viability and BLI signal as well as survival and osteogenic capacity of these cells ectopically in mice, they were seeded on ceramic scaffolds and implanted in immunodeficient rats at two levels in the spine for spinal fusion as well as subcutaneously. Nontransduced MSCs were used as a control group. All rats were monitored at day 1 and after that weekly until termination at week 7. In mice a BLI signal was observed during the whole observation period, indicating survival of the seeded MSCs, which was accompanied by osteogenic differentiation in vivo. However, these same MSCs showed a different response in the rat model, where the BLI signal was present until day 14, both in the spine and ectopically, indicating that MSCs were able to survive at least 2 weeks of implantation. Only when the signal was still present after the total implantation period ectopically, which only occurred in one rat, new bone was formed extensively and the implanted MSCs were responsible for this bone formation. Ectopically, neither a reduced proliferative group (irradiated) nor a group in which the cells were devitalized by liquid nitrogen and the produced extracellular matrix remained (matrix group) resulted in bone formation. This suggests that the release of soluble factors or the presence of an extracellular matrix is not enough to induce bone formation. For the spinal location, the question remains whether the implanted MSCs contribute to the bone regeneration or that the principal mechanism of MSC activity is through the release of soluble mediators. PMID- 20575657 TI - Platform switching for marginal bone preservation around dental implants: a systematic review and meta-analysis. AB - BACKGROUND: Platform switching for maintaining peri-implant bone levels has gained popularity among implant manufacturers over the last few years. However, the assumption that the inward shifting of the implant-abutment junction may preserve crestal bone was primarily based on serendipitous finding rather than scientific evidence. The objectives of the present study were to systematically review radiographic marginal bone-level changes and the survival of platform switched implants compared to conventional platform-matched implants. METHODS: A literature search of electronic databases (MEDLINE, EMBASE, The Cochrane Oral Health Group's Trials Register, The Cochrane Central Register of Controlled Trials, the U.K. National Research Register, the Australian New Zealand Clinical Trials Registry, the Database of Abstracts of Reviews of Effectiveness, and Conference Proceedings Citation Index) was performed up to March 15, 2010. Hand searches included several dental journals, and authors were contacted for missing information. Controlled trials that compared marginal bone-level changes around platform-switched dental implants with those restored with platform-matched prostheses were selected. The review and meta-analysis were done according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. Data were analyzed using two meta-analytic statistical packages. Mean differences (MDs) were calculated for analyzing continuous data, and risk ratios (RRs) were used for dichotomous data with 95% confidence intervals (CIs). RESULTS: Ten studies with 1,239 implants were included. The marginal bone loss around platform-switched implants was significantly less than around platform-matched implants (MD: -0.37; 95% CI: -0.55 to -0.20; P <0.0001). No statistically significant difference was detected for implant failures between the two groups (RR: 0.93; 95% CI: 0.34 to 2.95; P = 0.89). Subgroup analyses showed that an implant-abutment diameter difference > or= 0.4 was associated with a more favorable bone response. CONCLUSIONS: The review and meta-analysis show that platform switching may preserve interimplant bone height and soft tissue levels. The degree of marginal bone resorption is inversely related to the extent of the implant-abutment mismatch. Further long-term, well-conducted, randomized controlled studies are needed to confirm the validity of this concept. PMID- 20575658 TI - New evidence suggests Southern China as a common source of multiple clusters of highly pathogenic H5N1 avian influenza virus. AB - Highly pathogenic H5N1 avian influenza is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A global effort is underway to control or eradicate the highly pathogenic H5N1 avian influenza virus in poultry and prevent human exposure, both of which may also reduce the risk of pandemic emergence. Hemagglutinin gene sequences from 215 human H5N1 influenza viruses were used to trace the source and dispersal pattern of human H5N1 influenza viruses on a global scale. A mutation network and phylogenetic analyses of the hemagglutinin gene show that human H5N1 influenza viruses can be clearly divided among 4 clusters across geographic space. On the basis of analysis of the N-glycosylation sites at positions 100 and 170 in the hemagglutinin protein, human H5N1 influenza viruses were also divided into 3 types. When we combined these analyses with geographic information system data analyses, we found that Southern China is often a common source of multiple clusters of H5N1 influenza viruses and that each cluster has different dispersal patterns and individual evolutionary features. In summary, the genetic evidence presented here provides clear evidence for multiple clusters of human H5N1 influenza viruses that initially originated in Southern China. PMID- 20575659 TI - Increased level of arginase activity correlates with disease severity in HIV seropositive patients. AB - Infection with human immunodeficiency virus (HIV) results in a chronic infection that progressively impairs the immune system. Although depletion of CD4(+) T cells is frequently used to explain immunosuppression, chronicity of infection and progressive loss of CD4(+) T cells are not sufficient to fully account for immune dysregulation. Arginase-induced l-arginine deprivation is emerging as a key mechanism for the down-regulation of immune responses. Here, we hypothesized that the level of arginase activity increases with disease severity in HIV seropositive patients. We determined the levels of arginase activity in peripheral blood mononuclear cells from HIV-seropositive patients and uninfected control participants. Our results show that peripheral blood mononuclear cells from HIV-seropositive patients with low CD4(+) T cell counts expressed statistically significantly higher levels of arginase activity, compared with patients with high CD4(+) T cell counts or uninfected control participants. Furthermore, we found a statistically significant correlation between high level of arginase activity and high viral load in HIV-seropositive patients. PMID- 20575660 TI - Toll-like receptor agonists allow generation of long-lasting antipneumococcal humoral immunity in response to a plain polysaccharidic vaccine. AB - Toll-like receptors (TLRs) are considered as potential targets for vaccine adjuvants. Here, we explored the impact of TLR agonists on the B cell response to a prototypic thymus-independent (TI) antigen: a Streptococcus pneumoniae capsular polysaccharide (PS). In adult mice, all TLR agonists (and CpG oligodeoxynucleotides [ODN] in particular) enhance the PS antibody response, provided that their administration is delayed until the second day after PS vaccination. In infant mice, CpG ODN not only potentiated the PS3 antibody response but also restored responsiveness to PS3 vaccination. Moreover, the immune protection induced by the plain PS3 vaccine adjuvanted by CpG ODN was comparable to that conferred by the conjugate vaccine in terms of efficiency and longevity. CpG ODN exert their adjuvant effect by increasing the survival rate of antigen-stimulated B cells as well as the output of plasmablasts. Our results provide a rationale for broader application of polysaccharidic vaccines. PMID- 20575661 TI - Interleukin 17 receptor signaling is deleterious during Toxoplasma gondii infection in susceptible BL6 mice. AB - Th17 cells are involved in host defense against several pathogens. Using interleukin (IL) 17RA-deficient mice, we demonstrated reduced ileitis with diminished neutrophil recruitment and inflammatory lesions in the ileum, in the regional lymph node, in the spleen, and in the liver at day 7 and prolonged survival after Toxoplasma gondii infection. In addition, IL-17A antibody neutralization reduced inflammation and enhanced survival in BL6 mice. Diminished inflammation is associated with augmented interferon (IFN) gamma serum levels and enhanced production of IL-10 and IFN-gamma in cultured splenocytes upon antigen restimulation. Finally, cyst load and inflammation in the brain at 40 days are greater in surviving BL6 mice than in IL-17RA-deficient mice. In conclusion, oral T. gondii infection increases IL-17 expression and contributes to the inflammatory response, and IL-17 neutralization has a partial protective effect against fatal T. gondii-associated inflammation. PMID- 20575662 TI - Chronic norovirus infection after kidney transplantation: molecular evidence for immune-driven viral evolution. AB - BACKGROUND: Norovirus infection is the most common cause of acute self-limiting gastroenteritis. Only 3 cases of chronic norovirus infection in adult solid organ transplant recipients have been reported thus far. METHODS: This case series describes 9 consecutive kidney allograft recipients with chronic norovirus infection with persistent virus shedding and intermittent diarrhea for a duration of 97-898 days. The follow-up includes clinical course, type of immunosuppression, and polymerase chain reaction for norovirus. Detailed molecular analyses of virus isolates from stool specimens over time were performed. RESULTS: The intensity of immunosuppression correlated with the diarrheal symptoms but not with viral shedding. Molecular analysis of virus strains from each patient revealed infection with different variants of GII.4 strains in 7 of 9 patients. Another 2 patients were infected with either the GII.7 or GII.17 strain. No molecular evidence for nosocomial transmission in our outpatient clinic was found. Capsid sequence alignments from follow-up specimens of 4 patients showed accumulation of mutations over time, resulting in amino acid changes predominantly in the P2 and P1-2 region. Up to 25 amino acids mutations were accumulated over a 683-day period in the patient with an 898-day shedding history. CONCLUSION: Norovirus infection may persist in adult renal allograft recipients with or without clinical symptoms. No evidence for nosocomial transmission in adult renal allograft recipients was found in our study. Molecular analysis suggests continuous viral evolution in immunocompromised patients who are unable to clear this infection. PMID- 20575663 TI - Hepatitis C virus infections from unsafe injection practices at an endoscopy clinic in Las Vegas, Nevada, 2007-2008. AB - BACKGROUND: In January 2008, 3 persons with acute hepatitis C who all underwent endoscopy at a single facility in Nevada were identified. METHOD: We reviewed clinical and laboratory data from initially detected cases of acute hepatitis C and reviewed infection control practices at the clinic where case patients underwent endoscopy. Persons who underwent procedures on days when the case patients underwent endoscopy were tested for hepatitis C virus (HCV) infection and other bloodborne pathogens. Quasispecies analysis determined the relatedness of HCV in persons infected. RESULTS: In addition to the 3 initial cases, 5 additional cases of clinic-acquired HCV infection were identified from 2 procedure dates included in this initial field investigation. Quasispecies analysis revealed 2 distinct clusters of clinic-acquired HCV infections and a source patient related to each cluster, suggesting separate transmission events. Of 49 HCV-susceptible persons whose procedures followed that of the source patient on 25 July 2007, 1 (2%) was HCV infected. Among 38 HCV-susceptible persons whose procedures followed that of another source patient on 21 September 2007, 7 (18%) were HCV infected. Reuse of syringes on single patients in conjunction with use of single-use propofol vials for multiple patients was observed during normal clinic operations. CONCLUSIONS: Patient-to-patient transmission of HCV likely resulted from contamination of single-use medication vials that were used for multiple patients during anesthesia administration. The resulting public health notification of approximately 50,000 persons was the largest of its kind in United States health care. This investigation highlighted breaches in aseptic technique, deficiencies in oversight of outpatient settings, and difficulties in detecting and investigating such outbreaks. PMID- 20575664 TI - Effect of clinical and virological parameters on the level of neutralizing antibody against pandemic influenza A virus H1N1 2009. AB - BACKGROUND: Little is known about the antibody response in natural infection by the novel 2009 influenza A (H1N1) virus and its relationship with clinical and virological parameters. The relative lack of background neutralizing antibody against this novel virus provides a unique opportunity for understanding this issue. METHODS: Case patients presenting with influenza-like illness who were positive for the pandemic H1 gene by reverse transcription polymerase chain reaction were identified. The serum antibody response was assayed by neutralizing antibody titer (NAT) against the virus in 881 convalescent donors. We retrospectively analyzed clinical parameters and viral load. RESULTS: Ninety percent of the 881 convalescent donors had seroprotective titer of 1:40 or greater. The geometric mean titer of donors with convalescent NAT measured between day 21 and 42 was 1:101.1. Multivariate analysis by ordinal regression showed that pneumonia (odds ratio, 3.39; 95% confidence interval, 1.49-7.61; P = .004) and sputum production (odds ratio, 1.75; 95% CI, 1.01-3.01; P = .046) were the 2 independent factors associated with a higher level of convalescent NAT. Being afebrile on influenza presentation was associated with subsequent poor NAT (<1:40) response (P = .04). A positive correlation between the nasopharyngeal viral load on presentation and the convalescent NAT was demonstrated (Spearman correlation rho, 0.238; P = .026). CONCLUSIONS: About 10% of these convalescent patients do not have a seroprotective NAT and may benefit from vaccination to prevent reinfection. The convalescent NAT correlated well with the initial viral load and was independently associated with severity of the viral illness, including pneumonia. The findings provide both the clinical and virological markers for identifying potential convalescent plasma donors with high serum NAT, which can be used to produce hyperimmune intravenous immunoglobulin in a randomized treatment trial for patients with severe pandemic H1N1 infection. PMID- 20575665 TI - Brain abscess as a complication of intranasal ethmoidectomy for sinonasal polyposis. PMID- 20575666 TI - Phlegmonous gastritis and group A streptococcal toxic shock syndrome in a patient following functional endoscopic sinus surgery. AB - BACKGROUND: Phlegmonous gastritis is a rare and often fatal condition that can affect healthy individuals in 50% of cases. The condition has been described in accounts dating back to the pre-antibiotic era, during which time mortality was nearly 100%. Over the past century, case reports average about one per year. The etiology remains unclear, although Streptococcus species is isolated frequently. The optimum treatment has not been delineated clearly but likely involves a combination of antibiotics with or without surgical resection. METHODS: A case report was presented and the pertinent literature was reviewed. CASE REPORT: A 45 year-old man with a history of recent paranasal sinus surgery presented with acute abdominal pain and criteria consistent with toxic shock syndrome. Computed tomography scan showed diffuse thickening of the gastric wall and free intraperitoneal fluid. Exploratory laparotomy revealed a thickened stomach wall with outer fibrinous exudate and murky peritoneal fluid, which grew Streptococcus pyogenes. Intraoperative esophagogastroduodenoscopy revealed thickened gastric folds with a "cobblestone" appearance and no evidence of perforation. He was treated with antibiotics intravenously and sustained a difficult intensive care unit course complicated by ventilator-dependent respiratory failure, renal failure, and coagulopathy, but survived without major disability. CONCLUSIONS: This is an unusual case presentation of a rare but potentially lethal condition, whose optimal treatment is unclear. Phlegmonous gastritis should be considered when isolated gastric wall thickening is encountered in the clinical setting of toxic shock syndrome. PMID- 20575667 TI - Adaptive distance measures for resolving K2P quartets: metric separation versus stochastic noise. AB - Distance-based phylogenetic reconstruction methods use the evolutionary distances between species in order to reconstruct the tree spanning them. The evolutionary distance between two species, which is computed from their DNA (or protein) sequences, is typically considered as a fixed function of these sequences, predetermined by the assumed model of evolution. This article continues the line of research that attempts to adjust to each given set of input sequences a distance function which maximizes the expected accuracy of the reconstructed tree. Specifically, we present methods for selecting distance functions that considerably improve the accuracy of quartets constructed by the four-point method in Kimura's 2-parameter model, where special emphasis is given to the case of non-homogenous quartets. PMID- 20575668 TI - Modeling algae growth in an open-channel raceway. AB - Cost-effective implementation of microalgae as a solar-to-chemical energy conversion platform requires extensive system optimization; computer modeling can bring this to bear. This work uses modified versions of the U.S. Environmental Protection Agency's (EPA's) Environmental Fluid Dynamics Code (EFDC) in conjunction with the U.S. Army Corp of Engineers' water-quality code (CE-QUAL) to simulate hydrodynamics coupled to growth kinetics of algae (Phaeodactylum tricornutum) in open-channel raceways. The model allows the flexibility to manipulate a host of variables associated with raceway-design, algal-growth, water-quality, hydrodynamic, and atmospheric conditions. The model provides realistic results wherein growth rates follow the diurnal fluctuation of solar irradiation and temperature. The greatest benefit that numerical simulation of the flow system offers is the ability to design the raceway before construction, saving considerable cost and time. Moreover, experiment operators can evaluate the impacts of various changes to system conditions (e.g., depth, temperature, flow speeds) without risking the algal biomass under study. PMID- 20575669 TI - A pilot study to assess lung deposition of HFA-beclomethasone and CFC beclomethasone from a pressurized metered dose inhaler with and without add-on spacers and using varying breathhold times. AB - BACKGROUND: The study objective of this pilot study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP; QVARTM) and CFC beclomethasone dipropionate (CFC-BDP; BecloforteTM) with and without the add-on spacers, AerochamberTM, and VolumaticTM. The smaller particles of HFA-BDP were presumed to produce greater lung deposition using spacers, with and without a delay [i.e., metered dose inhaler (MDI) actuation into the spacer and subsequent inhalation 0 and 2 sec later], compared with the larger particles of CFC-BDP. The study included a comparison of breathhold effects (i.e., 1 and 10-sec breatholds) on lung deposition. METHODS: The study was an open-label design and utilized healthy subjects (n = 12 males). Each arm of the study contained three subjects; thus, outcomes were not powered to assess statistical significance. HFA-BDP and CFC-BDP were radiolabeled with technetium-99m and delivered to subjects. RESULTS: Results showed that the small particle HFA-BDP lung deposition averaged 52% and was not affected by the use of Aerochamber with or without a spacer delay. The oropharyngeal deposition of HFA-BDP was reduced from approximately 28% to 4% with the Aerochamber. Lung deposition with the large particle CFC-BDP was 3-7% and generally decreased with Aerochamber or Volumatic. A 2-sec time delay between actuation and breath plus the spacer reduced lung deposition slightly but reduced oropharygeal deposition substantially (84% down to 3-20%) using the Aerochamber or Volumatic with and without a spacer delay. HFA-BDP lung deposition was dependent on the breathhold. Lung deposition with HFA-BDP was reduced by 16% with a 1-sec versus 10-sec breathhold. The difference was measured in the increased exhaled fraction, confirming that smaller particles need time to deposit and are exhaled if there is a reduced breathhold. The large particle CFC-BDP lung deposition was not affected by breathhold. CONCLUSIONS: The use of Aerochamber or Volumatic spacers with HFA-BDP did not alter lung deposition but it did reduce oropharyngeal deposition. However, HFA-BDP displayed reduced oropharyngeal deposition without a spacer. PMID- 20575670 TI - Cardiac effects of "mad honey": a case series. AB - BACKGROUND: Grayanotoxins (GTX), also known as andromedotoxins, are produced by plants of the Ericacae family. This toxin is responsible for "mad honey" intoxication, which can present with fatal cardiac bradyarrhythmias and circulatory collapse. GTXs lead to cardiac toxicity because they increase sodium channel permeability and activate the vagus nerve. OBJECTIVE: We evaluated 42 patients (33 males) prospectively who had been hospitalized with diagnosis of "mad honey" intoxication in a state hospital setting. METHODS AND RESULTS: The median age of patients was 48.5 years and all patients were admitted with complaints of nausea, vomiting, dizziness, fainting, and sweating. Five of the patients had syncope before admission. On admission, the mean systolic blood pressure was 73.1 +/- 12.7 mmHg, the mean diastolic blood pressure was 52.1 +/- 11.3 mmHg, mean heart rate was 38 +/- 7 bpm. On initial electrocardiograms, 18 patients had sinus bradycardia, 15 patients had complete atrioventricular block, and 9 patients had nodal rhythm. All patients were monitored in a coronary care unit and treated symptomatically with atropine, intravenous fluids, and dopamine. None of the patients needed temporary pacing and all were discharged without complications. CONCLUSION: "Mad honey," which is produced widely in northern parts of Turkey can be toxic. This intoxication should be considered in patients admitted to emergency department with bradycardia and hypotension especially in regions where this honey is produced. PMID- 20575671 TI - Hydrogen peroxide ingestion associated with portal venous gas and treatment with hyperbaric oxygen: a case series and review of the literature. AB - INTRODUCTION: Ingestion of concentrated hydrogen peroxide (H(2)O(2)) has been associated with venous and arterial gas embolic events, hemorrhagic gastritis, gastrointestinal bleeding, shock, and death. Although H(2)O(2) is generally considered a benign ingestion in low concentrations, case reports have described serious toxicity following high concentration exposures. Hyperbaric oxygen (HBO) has been used with success in managing patients suffering from gas embolism with and without manifestations of ischemia. METHODS: Poison center records were searched from July 1999 to January 2010 for patients with H(2)O(2) exposure and HBO treatment. Cases were reviewed for the concentration of H(2)O(2), symptoms, CT scan findings of portal gas embolism, HBO treatment, and outcome. RESULTS; Eleven cases of portal gas embolism were found. Ages ranged from 4 to 89 years. All but one ingestion was accidental in nature. In 10 cases 35% H(2)O(2) was ingested and in 1 case 12% H(2)O(2) was ingested. All abdominal CT scans demonstrated portal venous gas embolism in all cases. Hyperbaric treatment was successful in completely resolving all portal venous gas bubbles in nine patients (80%) and nearly resolving them in two others. Ten patients were able to be discharged home within 1 day, and one patient had a 3.5-day length of stay. CONCLUSIONS: HBO was successful in resolving portal venous gas embolism from accidental concentrated H(2)O(2) ingestions. PMID- 20575672 TI - New approach to study the mechanism of antimicrobial protection of an active packaging. AB - This article reports on the antimicrobial efficiency of a new active packaging concept based on the use of two essential oils (cinnamon and oregano) and their chemical descriptors (cinnamaldehyde, thymol, and carvacrol) against the Gram positive bacterium Listeria monocytogenes, the Gram-negative bacterium Salmonella choleraesuis, the yeast Candida albicans, and the mold Aspergillus flavus. Complete inhibition of these microorganisms with either bactericidal or bacteriostatic effect has been demonstrated. It has been proven that the inhibition provided by these solutions is related not to the total amount of the active chemical released but to the amount of active compounds that reach the agar surface at a critical time. This critical time is notably related with the duration of the lag phase, as demonstrated for the bacteria, and shows that kinetic behavior has a critical role in the antimicrobial properties of the active packaging. Two different active films, polypropylene and the complex polyethylene-ethylenvynil alcohol, have been studied and a higher efficiency was found for polypropylene, mainly because of the mentioned kinetic reasons. These results can be used to understand the mechanism of action of the chemicals and provide valuable data for the development of the active packaging concept. PMID- 20575673 TI - Enteric bacterial pathogens with zoonotic potential isolated from farm-raised deer. AB - The raising of captive white-tailed deer (Odocoileus virginianus) is a growing agricultural industry in Ohio as it is in several other areas of the United States and around the world. Pooled fecal samples were collected from 30 white tailed deer confinement facilities. Samples were cultured for five enteric bacterial pathogens. Premise prevalence rates were as follows: Escherichia coli O157, 3.3%; Listeria monocytogenes, 3.3%; Salmonella enterica, 0%; Yersinia enterocolitica, 30%; and Clostridium difficile, 36.7%. The ail virulence gene could not be amplified from any of the Y. enterocolitica isolates recovered. Toxigenic strains of C. difficile polymerase chain reaction ribotype 078, an emerging C. difficile genotype of humans and food animals, were recovered from 4 of 11 (36.4%) C. difficile-positive deer farms. Venison from farm-raised deer might become contaminated with foodborne pathogens, deer farmers may have occupational exposure to these zoonotic agents, and farm-raised deer could be a reservoir from which the environment and other livestock may become contaminated with a number of potentially zoonotic bacteria. PMID- 20575674 TI - Inactivation of human enteric virus surrogates by high-intensity ultrasound. AB - Foodborne viruses, especially human noroviruses, are recognized as leading causes of nonbacterial gastroenteritis worldwide. Development of effective inactivation methods is of great importance to control their spread. In this study, the effect of high-intensity ultrasound (HIUS) on the infectivity of three foodborne virus surrogates was investigated. The three surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), and MS2 bacteriophage, were diluted in phosphate buffered saline (PBS) or orange juice to a titer of approximately 6 log(10) PFU/mL or approximately 4 log(10) PFU/mL. The ultrasound treatment was performed in duplicate by immersing the HIUS probe in virus-containing solution that was cooled in ice-water and sonicated at 20 kHz for 2, 5, 10, 15, 20, and 30 min with 30 sec on and 30 sec off. The infectivity of the recovered viruses after each ultrasound treatment was evaluated in duplicate using standardized plaque assays and compared to untreated controls. The results show that HIUS effectiveness depended on the virus type, the initial titer of the viruses, and the virus suspension solution. At titers of approximately 4 log(10) PFU/mL in PBS, feline calicivirus (FCV)-F9, MS2, and murine norovirus (MNV)-1 required 5-, 10-, and 30 min treatment, respectively, for complete inactivation. At initial titers of approximately 4 log(10) PFU/mL in orange juice, FCV-F9 required a 15-min treatment for complete inactivation and only a 1.55 log(10) PFU/mL reduction was achieved for MNV-1 in orange juice after 30-min treatment. Thus, inactivation by HIUS in orange juice was much lower than in PBS. Experiments using titers of approximately 6 log(10) PFU/mL showed decreased effects compared to those using titers of approximately 4 log(10) PFU/mL. These results indicate that HIUS alone is not sufficient to inactivate virus in food. Hurdle technologies that combine HIUS with antimicrobials, heat, or pressure should be explored for viral inactivation. PMID- 20575675 TI - Comparison of percutaneous and laparoscopic renal cryoablation for small (<3.0 cm) renal masses. AB - PURPOSE: We reviewed our experience with laparoscopic cryoablation (LCA) and percutaneous cryoablation (PCA) in the management of small renal tumors and compared clinical outcomes, short-term oncologic results, and patient complications. PATIENTS AND METHODS: A retrospective comparison of two prospectively collected oncologic databases was performed. Ninety patients underwent PCA for 99 lesions and 81 patients underwent an LCA for 97 lesions. Patient characteristics, perioperative data, and tumor characteristics were recorded including age, estimated blood loss, complication rate, tumor size, and tumor pathology. RESULTS: Patients in both the PCA and LCA groups had similar demographic and tumor characteristics. The PCA group had two major complications (2%), and the LCA group had three major complications (3.7%) (P = 0.374). In the LCA group, estimated blood loss was associated with tumor location with hilar tumor demonstrating a significantly higher mean blood loss (191 mL) compared with endophytic, mesophytic, and exophytic tumors (70 mL, 71 mL, 73.5 mL), respectively (P = 0.05). Malignancies rated in the PCA and LCA groups were 50.5% and 60.0%, respectively (P < 0.05). In the PCA group, nine (9.1%) patients demonstrated treatment failure with a persistent enhancement in the ablation bed. All nine were treated with a subsequent PCA. One patient had subsequent tumor bed enhancement and underwent an open radical nephrectomy. Treatment failed in three (3.1%) patients in the LCA cohort (incomplete ablation or recurrence). CONCLUSIONS: With short-term follow-up, both LCA and PCA are safe and effective treatments for small renal masses. Patients undergoing PCA had a reduced hospital stay and a lower surgical complication rate, albeit with an elevated re-treatment rate. Long-term data is needed to establish long-term oncologic efficacy. Renal function did not significantly change in patients after cryoablation, including patients with a solitary kidney. PMID- 20575676 TI - The osteoconductivity of biomaterials is regulated by bone morphogenetic protein 2 autocrine loop involving alpha2beta1 integrin and mitogen-activated protein kinase/extracellular related kinase signaling pathways. AB - It is critical to understand the complex interactions between cells and scaffolds for a successful tissue engineering approach for bone regeneration. Beyond providing structural support for the cells, synthetic scaffolds act together with some soluble biofactors through intracellular signaling pathways to provide the appropriate clues for cells to form bone tissue. The aim of this study was to investigate the mechanism by which beta-tricalcium phosphate (beta-TCP), a clinically used bone graft substitute, exerts its osteoconductivity on primary human osteoblasts. Culturing human osteoblasts on beta-TCP scaffold for 1 and 7 days induced gene expression of bone morphogenetic protein 2 (BMP2) and its receptors and activated its downstream Smad1/5 signaling pathway, which were orchastrated with induced osteoblastic differentiation. Blocking BMP2 activity by its inhibitor (Noggin) led to the abrogation of osteoblastic differentiation and partially inhibited Smad1/5 signaling pathway. Finally, blocking alpha2beta1 integrin or inhibiting mitogen-activated protein kinase/extracellular related kinase signaling pathway attenuated the induction of gene expression of BMP2 and its receptors and the activation of Smad1/5 signaling pathway. We concluded that beta-TCP scaffold promotes osteoblastic differentiation by a BMP2 autocrine loop, a process involving alpha2beta1 integrin and mitogen-activated protein kinase/extracellular related kinase signaling pathways. The findings of this study might provide a useful principle for fabricating or designing an ideal scaffold for bone tissue engineering. PMID- 20575677 TI - Developing a public health research agenda for women with blood disorders. AB - Bleeding and clotting in women is an issue that directly affects the life of every woman, child, and family worldwide. This article summarizes recent activities undertaken by the Division of Blood Disorders (DBD) at the Centers for Disease Control and Prevention (CDC) to identify risk factors through evidence based research and surveillance to prevent complications of blood disorders in women. Specific focus is given to our efforts to improve early identification and diagnosis of blood disorders among women, improve our understanding of maternal and infant outcomes, and develop surveillance systems to monitor the prevalence and incidence of these events. PMID- 20575678 TI - Perspectives on evidence-based healthcare for women. PMID- 20575680 TI - Examining the diverse perspectives of nurse practitioners regarding obstacles to diaphragm prescription: a latent class analysis. AB - BACKGROUND: The diaphragm is receiving renewed attention not only for its dual method potential but also because of improved design. To facilitate method re introduction, we examined what providers think about this female-controlled barrier contraceptive. METHODS: A questionnaire administered to 450 women's health nurse practitioners (NPs) asked about their practice experience and issues concerning diaphragm use. Latent class analysis (LCA) was used to identify different groups of providers, based on patterns of perceptions regarding various potential obstacles to diaphragm use. Provider profiles were further described in terms of individual and practice characteristics. RESULTS: The survey achieved a 47% response rate (n = 214). Respondents saw, on average, 31 family planning patients/week; 87% had fitted a diaphragm, although only 40% had done so in the previous year. Three groups holding significantly different perceptions of obstacles to diaphragm prescription were identified. Group 1 (13% of respondents), with more practice experience in delivering women's healthcare and fitting diaphragms, considered all obstacles relatively inconsequential. Group 2 (40%) had comparatively minor concerns, whereas Group 3 (47%) perceived all issues as major obstacles. All groups stressed the diaphragm's limited promotion, and for 87% of the respondents, concerns about effectiveness and nonfamiliarity with the method also assumed more salience. CONCLUSIONS: Emerging statistical modeling approaches that go beyond standard aggregate analyses helped identify three groups of women's health nurse practitioners. By considering their diverse perceptions of potential obstacles to diaphragm use, strategies aimed at changing provider behaviors may be developed to reverse declining prescribing rates and retain the diaphragm as a viable reproductive healthcare option for women. PMID- 20575681 TI - Using cancer registry data for recruitment of sexual minority women: successes and limitations. AB - OBJECTIVE: To identify and recruit an unknown and presumably small subgroup of survivors, that is, lesbian or bisexual women with breast cancer. METHODS: This report describes our multistep approach to recruit a representative sample of heterosexual and sexual minority breast cancer survivors. We used census data to identify geographic areas with a greater prevalence of sexual minority women (SMW), that is, lesbian and bisexual women. We then obtained the breast cancer cases from a cancer registry for these geographic areas. In the absence of sexual orientation data in cancer registries, all potentially eligible women with breast cancer needed to be contacted by telephone to determine their sexual orientation. RESULTS: Among the 1341 women screened who answered the question about sexual orientation, 6.3% were SMW. Overall, we processed 4143 cases to obtain completed data on 69 SMW and 257 heterosexual women with breast cancer. CONCLUSIONS: Our findings suggest that it is resource intensive but feasible to recruit a representative sample of breast cancer survivors of different sexual orientations. Our findings can inform future studies that seek to recruit sexual minority populations from cancer registries about some of the limitations to this approach. PMID- 20575682 TI - A question of balance. PMID- 20575683 TI - Cardioprotective effect of periodontal therapy in metabolic syndrome: a pilot study in Indian subjects. AB - BACKGROUND: Obesity, metabolic syndrome, and atherosclerosis are linked with an increased acute-phase response. Severe periodontal disease is associated with cardiovascular disease as sequelae of a systemic inflammatory response. OBJECTIVE: The aim of this study was to assess changes in measures of systemic inflammation induced by periodontal therapy in periodontally diseased individuals with metabolic syndrome, compared to those induced in a systemically healthy group. METHODS: A total of 31 subjects with chronic generalized periodontitis, including 16 subjects with metabolic syndrome (group A) and 15 systemically healthy subjects (group B), underwent nonsurgical periodontal therapy. Serum high sensitivity C-reactive protein (hsCRP), total leukocyte count, and measures of lipid metabolism were measured at baseline and at 2 months after periodontal therapy. Baseline data for comparison was also obtained from 15 systemically and periodontally healthy individuals (group C). RESULTS: Baseline periodontal parameters and serum CRP were significantly higher in group A than in group B. In group A, following periodontal therapy, a significant decrease was noted in mean serum CRP (3.28 +/- 1.4 mg/L to 2.6 +/- 1.5 mg/L), total leukocyte counts (8,322 +/- 1,888 cells/mm(3) to 6,361 +/- 1,426 cells/mm(3)), serum triglycerides (153.3 +/- 38 mg/dL to 121.0 +/- 28.57 mg/dL), along with a significant rise in serum high-density lipoprotein (HDL) (41.1 +/- 5.2 mg/dL to 44.37 +/- 6.7 mg/dL). In group B, changes in these parameters were not statistically significant. Mean serum low-density lipoprotein (LDL) and mean cholesterol levels did not change significantly in either group. CONCLUSIONS: Periodontal therapy produced significant modulation of serum hsCRP, total leukocytes, serum triglycerides, and HDL, and thus may benefit individuals affected with both metabolic syndrome and advanced periodontal disease. PMID- 20575684 TI - Drilling through impacted ureteral stones: use of the atherectomy rotablator device for urolithiasis. AB - BACKGROUND AND PURPOSE: The Rotablator is an angioplasty device that is passed over a wire. It uses a high-speed rotational "burr" (2 mm in diameter) that is coated with microscopic diamond particles and cooled by saline. It rotates at high speed (approximately 200,000 rpm) breaking up endovascular blockage into minute (smaller than red blood cells) fragments. We investigated, in vitro and ex vivo, the possible use of the Rotablator for urinary stone disease. MATERIALS AND METHODS: Human stones of different sizes and composition were used for the experiment. Stone impaction in vitro was modeled by wedging the stones into the proximal part of a 16F silicone Foley catheter. Likewise, an ex-vivo study was performed on stones placed into a freshly harvested swine ureter using a nitinol basket. Data regarding the drill time, remaining stone size, and ureteral damage were collected. RESULTS: Overall, 15 stones were treated (10 in vitro and 5 ex vivo). The device successfully drilled through all the stones, along the path of the guidewire, allowing complete passage of the burr. The pretreatment mean stone size for the silicone and ureteral testing was 65 mm(3) and 34 mm(3), respectively (both P < 0.01). The post-treatment size was 54 mm(3) and 24 mm(3), respectively. Average treatment time was 100 seconds. No visual macroscopic ureteral damage or perforation was observed. CONCLUSIONS: In vitro, the Rotablator is capable of drilling through stones with minimal damage. Drilling, however, occurred alongside the stone in which the guidewire was located and, thus, stone fragmentation appears to be minimal. Further studies are necessary to investigate other burr configurations and the use of the Rotablator for the fluoroscopic-guided passage of ureteral impaction in difficult clinical settings. PMID- 20575685 TI - Do patients benefit from miniaturized tubeless percutaneous nephrolithotomy? A comparative prospective study. AB - BACKGROUND AND PURPOSE: A benefit of miniaturized percutaneous nephrolithotomy (MPCNL) compared with conventional percutaneous nephrolithotomy (PCNL) has not been demonstrated as yet. Thus, the aim of this study was to evaluate the outcome of conventional vs MPCNL and to determine if MPCNL offers an advantage for the patient. PATIENTS AND METHODS: A prospective, nonrandomized series of 50 consecutive patients with solitary calculi (lower pole or the renal pelvis) were treated either by conventional PCNL (26F) or MPCNL (18F). Ultrasound or holmium laser were used for lithotripsy. Patients were treated tubeless after uncomplicated MPCNL, with thrombin-matrix tract closure and antegrade Double-J catheter placement. After PCNL, all patients received 22F nephrostomies. Demographic data, stone characteristics, perioperative course, and complication rates were assessed. RESULTS: Patients characteristics were comparable in both groups, except for stone size, which was 18 +/- 8 mm (MPCNL) and 23 +/- 9 (PCNL; P = 0.042). Operative time was comparable in both groups (48 +/- 17 vs 57 +/- 22 min, not significant [NS]). After MPCNL, 96% were stone free at day 1 vs 92% after PCNL (NS). Significant complications did not occur in both groups. Minor complications were: Fever, 12% (MPCNL) vs 20% (PCNL; NS); bleeding, 4% vs 8%; perforations, 0% vs 4% (all NS). Overall outcome was not influenced by body mass index. Calcium oxalate stones were predominant with 75%. Patients after tubeless MPCNL had less pain (visual analogue score, 3 +/- 3 vs 4 +/- 3; P = 0.048.) and needed slightly less additional pain medication (25 +/- 12 mg/d vs 37 +/- 10 mg/d piritramid; NS). Hospital stay was significantly shorter after MPCNL (3.8 +/- 28 vs 6.9 +/- 3.5 d; P = 0.021.). CONCLUSIONS: Both techniques were safe and effective for the management of renal calculi. While stone-free rates were comparable in our series, MPCNL showed advantages in terms of shorter hospital stay and postoperative pain. The lower stone burden and the tubeless fashion of MPCNL, however, might have influenced these results. PMID- 20575686 TI - Predicting effectiveness of extracorporeal shockwave lithotripsy by stone attenuation value. AB - PURPOSE: The aim of this study was to evaluate the effect of stone attenuation value on the effectiveness of extracorporeal shockwave lithotripsy (SWL) for upper urinary tract stones. METHODS: In this prospective study, 99 patients underwent SWL for solitary renal and upper ureteral stones from January 2007 to March 2009. All patients underwent CT scan before SWL. The mean attenuation value of stones in our study was 1213.3 +/- 314.5 Hounsfield units (HU). Group A consisted of 42 patients with stones of attenuation value <1200 HU and group B had 57 patients with stones of attenuation value >1200 HU. Stone size, location, requirement of number of shockwaves, shock intensities (power), retreatment rate, complication rate, auxiliary procedure rate, and effectiveness quotient (EQ) ratio were studied. RESULTS: The mean total number of shocks required to fragment the stones in groups A and B were 1317.1 +/- 345.3 and 1646.5 +/- 610.8, respectively (p = 0.001), with a mean shock intensity of 12.2 +/- 0.7 and 12.4 +/ 0.5 kV, respectively (p = 0.03). Retreatment was not required in patients of group A, but 14.03% patients in group B required retreatment (p < 0.0001). Clearance rate in group A was 88.1%, whereas in group B it was 82.5% (p = 0.35). Auxiliary procedure rates were 9.5% and 10.5% in groups A and B (p = 0.22), respectively. EQ was 80.4% and 66.2% in groups A and B (p = 0.03), respectively. Complication rates were similar with 2.4% and 3.5% in groups A and B, respectively (p = 0.37). Significant correlation was recorded for total number and intensity of shocks with stone attenuation value. CONCLUSIONS: The EQ of SWL for upper urinary tract stones was significantly better for stones with lower attenuation value. The number and intensity of shocks required to fragment these stones with lower attenuation value were also significantly lower. PMID- 20575687 TI - Long-term cancer-specific and overall survival for men followed more than 10 years after primary and salvage cryoablation of the prostate. AB - INTRODUCTION: Ten-year disease-specific survival for clinically localized prostate cancer after radiation is 93%, 88%, and 80% for low-, medium-, and high risk groups, respectively. The objective of this study was to report long-term cancer survival outcomes for patients who had undergone prostate cryotherapy at our institution more than 10 years ago. To date, this is the longest reported follow-up after cryotherapy. MATERIALS AND METHODS: A retrospective patient chart review, conducted of an Institutional Review Board (IRB)- approved cryotherapy database, identified 76 men who had undergone prostate cryotherapy before January 1999. Pre-, intra-, and posttreatment data were collected. Primary study endpoints were overall mortality and prostate-cancer-specific death. Secondary endpoints were disease recurrence and clinical progression. RESULTS: Mean patient age was 69.2 (47.4-86.3) years; median preoperative prostate-specific antigen was 5.3 (0.2-208.0); mean Gleason score was 7. Forty of 76 (52.6%) were confirmed D'Amico high risk. Median follow-up was 10.1 (0.2-14.9) years; 25 patients underwent primary treatment; 51 postradiation. After 10 years of follow-up, 43 of 76 men (56.6%) were still alive; 33 men (43.4%) had died-10 (13.2%) from prostate cancer, 18 (22.4%) from noncancerous causes, and 5 (6.6%) unknown. CONCLUSIONS: The long-term results of prostate cryotherapy in our series indicate an 87% overall 10-year prostate-cancer-specific survival, despite early cryotherapy technology and the majority of patients being D'Amico high risk. PMID- 20575688 TI - Synchronous bilateral laparoendoscopic single-site adrenalectomy. AB - Abstract We present the first report of simultaneous laparoendoscopic single-site surgery (LESS) for bilateral primary aldosterone-producing adrenal adenomas. A 40 year-old man with hypertension that was resistant to pharmacotherapy was shown to have bilateral aldosterone-producing adrenal adenomas. A right partial and a left total adrenalectomy were performed at the same time via a single umbilical incision. The surgery and recovery were uncomplicated. This is the first report of synchronous bilateral LESS. PMID- 20575689 TI - Conversion to hand assistance may prevent conversion to an open procedure in standard laparoscopic nephrectomy. AB - BACKGROUND AND PURPOSE: Laparoscopic surgery has received wide acceptance within the urologic community. Conversion from standard laparoscopy to the open technique may sometimes be necessary. Conversion to an open procedure may have negative implications for both the surgeon and the patient. Conversion to hand assisted laparoscopy under these circumstances, however, may obviate open surgery. We intended to review our results and emphasize the efficacy and safety of conversion to hand assistance during standard laparoscopy when necessary. PATIENTS AND METHODS: We retrospectively reviewed the results of laparoscopic nephrectomies performed by one surgeon. Demographic and perioperative data were noted. Conversions from standard laparoscopy were analyzed in detail. RESULTS: A total of 161 laparoscopic nephrectomies were performed. Conversion was deemed appropriate in 6 of 150 standard laparoscopies. Surgery was successfully completed in five with hand assistance. The reason to convert was failure to progress in three patients and control of hemostasis in two patients. Open surgery was performed in a patient who could not tolerate pneumoperitoneum. CONCLUSION: Conversion to hand-assisted laparoscopy is safe and effective when the surgeon decides to convert from standard laparoscopy. Conversion to hand assistance may prevent conversion to an open procedure in these situations. PMID- 20575690 TI - Automatic quantitative micro-computed tomography evaluation of angiogenesis in an axially vascularized tissue-engineered bone construct. AB - INTRODUCTION: We invented an automatic observer-independent quantitative method to analyze vascularization using micro-computed tomography (CT) along with three dimensional (3D) reconstruction in a tissue engineering model. MATERIALS AND METHODS: An arteriovenous loop was created in the medial thigh of 30 rats and was placed in a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix, filled with fibrin (10 mg/mL fibrinogen and 2 IU/mL thrombin) without (group A) or with (group B) application of fibrin-gel-immobilized angiogenetic growth factors vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF). The explantation intervals were 2, 4, and 8 weeks. Specimens were investigated by means of micro-CT followed by an automatic 3D analysis, which was correlated to histomorphometrical findings. RESULTS: In both groups, the arteriovenous loop led to generation of dense vascularized connective tissue with differentiated and functional vessels inside the matrix. Quantitative analysis of vascularization using micro-CT showed to be superior to histological analysis. The micro-CT analysis also allows the assessment of different other, more complex vascularization parameters within 3D constructs, demonstrating an early improvement of vascularization by application of fibrin-gel-immobilized VEGF165 and bFGF. CONCLUSIONS: In this study quantitative analysis of vascularization using micro-CT along with 3D reconstruction and automatic analysis exhibit to be a powerful method superior to histological evaluation of cross sections. PMID- 20575692 TI - Cyclin D1 G870A polymorphism is associated with risk and clinicopathologic characteristics of bladder cancer. AB - Cyclin D1 (CCND1) is a key protein in regulation of cell cycle at the G1-to-S transition phase and is essential for regulation of cell proliferation, differentiation, and transcriptional control. We hypothesized that the CCND1 G870A polymorphism is associated with risk of bladder cancer. The CCND1 G870A polymorphism was genotyped in a hospital-based case-control study of 402 bladder cancer cases and 402 control subjects using the polymerase chain reaction restriction fragment length polymorphism method. Unconditional univariate and multivariate logistic regression analyses were used to evaluate the associations between the CCND1 G870A polymorphism and bladder cancer risk. A significantly increased risk of bladder cancer was associated with the combined variant CCND1 870GA/AA genotypes (adjusted odds ratio, 1.54; 95% confidence interval, 1.08 2.20) compared with the GG genotype, particularly among subgroups of age >=65 years (1.74; 1.06-2.88), men (1.67; 1.15-2.44), and smokers (1.82; 1.12-2.93). Further, the G870A polymorphism was significantly associated with risk of developing superficial bladder cancer (grade 1). In addition, a meta-analysis of the G870A polymorphism and bladder cancer risk showed that the variant 870GA/AA genotypes were associated with an increased risk of bladder cancer in Asians, but not in Caucasians, which was consistent with the results of our study. The CCND1 G870A polymorphism may be a marker for the development of bladder cancer in Chinese populations. Larger studies are required to validate these findings in diverse populations. PMID- 20575691 TI - Adipose-derived mesenchymal stem cells treated with growth differentiation factor 5 express tendon-specific markers. AB - OBJECTIVES: Adipose-derived mesenchymal stem cells (ADMSCs) are a unique population of stem cells with therapeutic potential in the treatment of connective tissue injuries. Growth differentiation factor-5 (GDF)-5 is known to play a role in tendon repair and maintenance. The aim of this study was to investigate the effects of GDF-5 on proliferation and tendonogenic gene expression of rat ADMSCs. METHODS: ADMSCs were treated in culture with different concentrations of GDF-5 (0-1000 ng/mL) for 12 days. Biochemical, temporal, and concentration kinetic studies were done. Extracellular matrix (ECM) synthesis, tendonogenic differentiation, and matrix remodeling gene and protein expression were analyzed. RESULTS: GDF-5 led to increased ADMSC proliferation in a dose- and time-dependent manner. ADMSCs demonstrated enhanced ECM (collagen type I, decorin, and aggrecan) and tendonogenic marker (scleraxis, tenomodulin, and tenascin-C) gene expression with 100 ng/mL of GDF-5 (p < 0.05). ECM and tendon specific markers showed time-dependent increases at various time points (p < 0.05), although decorin decreased at day 9 (p < 0.05). GDF-5 did alter expression of matrix remodeling genes, with no specific trends observed. Western blot analysis confirmed dose- and time-dependent increases in protein expression of tenomodulin, tenascin-C, Smad-8, and matrix metalloproteinase-13. CONCLUSION: In vitro GDF-5 treatment can induce cellular events leading to the tendonogenic differentiation of ADMSCs. The use of combined GDF-5 and ADMSCs tissue-engineered therapies may have a role in the future of tendon repair. PMID- 20575694 TI - Intrarenal pressures generated during deployment of various antiretropulsion devices in an ex vivo porcine model. AB - INTRODUCTION: Pressurized saline irrigation is commonly used during ureteroscopy, which can cause an increase in intrarenal pressure leading to postoperative pain, sepsis, and renal injury due to pyelovenous and pyelolymphatic backflow. To prevent retrograde stone migration during ureteroscopic lithotripsy, antiretropulsion devices can be deployed, which may or may not protect the kidney against high intrarenal pressures. This study compares the intrarenal pressures generated during the use of two antiretropulsion devices in an ex vivo porcine model. MATERIALS AND METHODS: Using an ex vivo porcine model of the urinary system, flexible ureteroscopy was performed at the proximal, mid, and distal ureter. Intrarenal pressures were measured in the absence and presence of a coil based antiretropulsion device and a multifold film-based device. Intrarenal pressure measurements were obtained while using saline irrigation at a gravity of 84 cm H(2)O and pressures of 150 and 300 mm Hg. RESULTS: The deployment of a coil device resulted in a significant increase in intrarenal pressures during ureteroscopy with pressurized irrigation when compared with intrarenal pressures without a device. The use of a multifold film device that occluded the ureter during ureteroscopy resulted in a decrease in intrarenal pressures at an irrigation pressure of 300 mm Hg when compared with pressures without a device. In the remaining configurations, the intrarenal pressures were only minimally elevated. When comparing the two devices to each other, the multifold film device had significantly lower intrarenal pressures at each configuration. This has potential implications in preventing renal injury and/or sepsis during ureteroscopy. CONCLUSION: The use of a multifold film antiretropulsion device during ureteroscopy with high-pressure irrigation can potentially protect the kidney from elevated intrarenal pressures. PMID- 20575693 TI - Identification of PKHD1 multiexon deletions using multiplex ligation-dependent probe amplification and quantitative polymerase chain reaction. AB - INTRODUCTION: Mutations in the PKHD1 gene are responsible for autosomal recessive polycystic kidney disease (ARPKD). Using exon scanning by denaturing high performance liquid chromatography (dHPLC) or bidirectional sequencing of all exons constituting the longest open reading frame, the mutation detection rate reaches approximately 82% and minor lesion mutations include truncating, splice, and missense mutations. AIM: The main aim of this study was to screen ARPKD patients in whom only one pathogenic PKHD1 mutation was identified after bidirectional sequencing of the longest open reading frame, for gene copy number alterations by employing multiplex ligation-dependent probe amplification complemented with quantitative real-time polymerase chain reaction. RESULTS: Sixteen ARPKD probands were studied in whom only one clearly pathogenic mutation was previously identified. One patient with a suspected homozygous deletion of the exons 1-37 was also included in this cohort. Three distinct PKHD1 germ-line deletions were identified. Two of these deletions encompassed multiple exons of PKHD1 extending far beyond the 5' and 3' untranslated regions of the gene, and spanning at least 170 and 470 kb, respectively. The third 3.7 kb intragenic deletion affected only exons 20-21 of the PKHD1 gene. Thus, this is the first report presenting analysis of the entire PKHD1 longest open reading frame for gene deletions/duplications in a select cohort of ARPKD patients, in whom previously only one mutation was identified after bidirectional sequencing of the entire longest open reading frame. CONCLUSIONS: The data indicate that multiplex ligation-dependent probe amplification is a sensitive and rapid method to identify PKHD1 deletions. Our study demonstrates that dosage analysis will increase the PKHD1 mutation detection rate and should be performed as a complementary assay in patients suspected to have ARPKD in the absence of two clear pathogenic mutations. PMID- 20575695 TI - Multicenter experience with metallic ureteral stents for malignant and chronic benign ureteral obstruction. AB - BACKGROUND AND PURPOSE: A new coil-based metallic ureteral stent offers greater radial strength with longer indwelling time compared with plastic stents. This multicenter retrospective study reviews the clinical experience with this stent for malignant or benign chronic ureteral obstruction. PATIENTS AND METHODS: Patients had stent placement in a retrograde fashion. We analyzed preplacement and postplacement renal imaging to determine degree of hydronephrosis. Stent encrustation was determined by either visual inspection at the time of stent change or plain abdominal radiography. Preoperative and follow-up serum creatinine values were compared for each patient. RESULTS: A total of 76 stents in 59 renal units (40 patients) were successfully placed. Creatinine value follow up on 54 renal units showed 20 (37%) units to have stable, 15 (28%) improved, and 19 (35%) with worsening values. No stent showed encrustation on plain radiography despite it being seen on two during direct visualization. Three stents needed operative removal with either percutaneous nephrolithotomy or cystolitholapaxy. Fifteen of 41 (37%) metallic stents placed because of an obstructed plastic stent also became obstructed. At last follow-up, 6 of 40 patients were kept from nephrostomy tubes because of the metallic stent. CONCLUSIONS: Metallic stents are a viable alternative to nephrostomy tubes in patients in whom conventional stents fail because of malignant obstruction, but patients need to be followed closely. Stent encrustation that resulted in retained stents was poorly visualized on plain radiography. Patients still remain at risk for obstruction, urinary tract infections, and lower urinary tract symptoms from the metallic stent. PMID- 20575696 TI - Histotripsy of VX-2 tumor implanted in a renal rabbit model. AB - INTRODUCTION: Histotripsy is an extracorporeal focused ultrasound (US) technology that uses controlled cavitation to induce nonthermal mechanical tissue fractionation. Feasibility of histotripsy ablation of normal renal tissue in an in vivo rabbit model has previously been demonstrated. Our specific objective in this study was to characterize the histologic effects of histotripsy on VX-2 tumor implanted in the kidneys of an in vivo rabbit model. METHODS: VX-2 tumor was implanted below the renal capsule in 15 New Zealand white rabbits. Two weeks after implantation, tumors were localized with diagnostic US imaging. Targeted volumes within the observed tumor were treated with short (3 micros) pulses of 1 MHz acoustic energy at a repetition frequency of 300 Hz. Twenty tumors were treated with histotripsy and 7 served as tumor controls. Three normal kidneys were also treated with histotripsy. Kidneys and lungs were harvested, grossly inspected, and processed for histopathologic analysis. RESULTS: Real-time US imaging confirmed presence of cavitation during all histotripsy treatments. Examination of tumor and kidney specimens revealed 100% tumor growth with an average tumor diameter of 7 mm (range 2-12). In 16 of 20 tumors treated with histotripsy, acellular zones of debris and finely disrupted cellular architecture were present on histology. Kidneys harvested 24 hours after treatment revealed an extensive inflammatory reaction. CONCLUSIONS: Transcutaneous application of histotripsy to implanted VX-2 tumor in rabbit kidney produced fractionation of malignant tissue. These findings support the further study and development of histotripsy for potential oncologic application. PMID- 20575697 TI - Assessment of lymph node yield after pelvic lymph node dissection in men with prostate cancer: a comparison between robot-assisted radical prostatectomy and open radical prostatectomy in the modern era. AB - BACKGROUND AND PURPOSE: Studies of radical prostatectomy (RP) suggest that higher lymph node yield (LNY) improves tumor staging. Robot-assisted radical prostatectomy (RARP) is becoming increasingly popular, yet LNY data are not well reported. We compare LNY from contemporary open RP (ORP) with RARP at an academic center. PATIENTS AND METHODS: A retrospective study was conducted of an Urologic Oncology Database. Between January 2005 and November 2009, 217 men underwent ORP with pelvic lymph node dissection (PLND); 99 underwent RARP with PLND by a single surgeon during the same period. Men were stratified according to the D'Amico risk criteria. For intermediate and high-risk disease, an extended PLND was performed. Patient demographic, operative, and pathologic variables were measured, and LNY was compared across groups. RESULTS: No significant differences were seen between groups for race, body mass index, preoperative prostate-specific antigen level or biopsy Gleason score. Patients were younger for RARP vs ORP (P = 0.003) and had higher clinical tumor stage (P = 0.02). Operative time was longer (P = 0.03) and estimated blood loss was greater (P < 0.001) in the ORP group. Overall, only a borderline significant difference was seen in LNY between ORP and RARP (7.49 vs 6.35 nodes, respectively, P = 0.06). No difference was seen for intermediate and high-risk patients, with 7.7 vs 6.8 nodes for ORP and RARP, respectively (P = 0.27). The lymph node metastasis rate was 6.3%, with more positive nodes detected during ORP vs RARP: 19/217 (8.8%) vs 1/99 (1.0%), P = 0.009. CONCLUSIONS: No significant differences were seen in LNY during RARP and ORP for intermediate and high-risk men. For experienced surgeons, RARP can achieve equivalent LNY as ORP. A future study with a larger sample size is necessary to make a definitive statement of equivalence. PMID- 20575698 TI - Use of a flexible carbon dioxide laser fiber for precise dissection of the neurovascular bundle during robot-assisted laparoscopic prostatectomy. AB - INTRODUCTION: Carbon dioxide (CO(2)) lasers deliver energy with minimal thermal spread to tissues during dissection. Excess thermal spread during dissection of the neurovascular bundle (NVB) can affect potency in men after robot-assisted radical prostatectomy (RARP). We report on a novel delivery mechanism for CO(2) laser energy through a flexible fiber to enhance accuracy of NVB dissection during RARP. MATERIALS: A feasibility study of the OmniGuide BeamPath URO-LG CO(2) laser fiber for NVB dissection was performed on 10 patients with primary Gleason 3 T1c prostate cancer during RARP. Bilateral lateral fascial antegrade nerve sparing was performed. We evaluated fiber performance, safety, and efficacy. RESULTS: The fiber was inserted through the 12-mm assistant's port and easily manipulated by robotic instruments. Once pedicles were clipped and dissected, the laser fiber was effective in establishing planes of dissection between prostatic capsule and NVB. The endoscopically discernable thermal laser footprint was small, with minimal thermal spread during nerve sparing, meticulous dissection of NVB, and fascial layer identification. Although the laser did provide extremely accurate dissection, it was unable to serve as an adequate means of larger vessel coagulation. CONCLUSIONS: The flexible CO(2) laser fiber was easily manipulated. Identification of fascial layers during nerve sparing was facilitated with the fiber. Long-term follow-up is necessary to determine efficacy of this technology versus conventional techniques on the NVB. Larger studies are currently in progress to determine if use of the flexible CO(2) laser fiber results in improvements in functional outcomes with regard to return of sexual potency after RARP. PMID- 20575699 TI - The PolyScope: a modular design, semidisposable flexible ureterorenoscope system. AB - PURPOSE: To characterize the mechanical and optical properties of the PolyScope endoscope system and to examine the clinical outcome in patients who were undergoing ureteronephroscopy. MATERIALS AND METHODS: Mechanical assessment involved measurement of the deflection angle and irrigation flow rate. Optical resolution and distortion, field and angle of view, and light transmission and output formed the optical assessment. Clinical assessment was made in a series of consecutive ureteronephroscopy procedures. The optical cord was disconnected after each procedure, and the image fiber was assessed for damage. RESULTS: The mean value for the angle of maximum active tip deflection with an empty working channel was 265 degrees (261-275 degrees). Deflection was impaired most with insertion of the 3.0 F basket (10% decrease) and least with an indwelling 220 microm laser fiber (2% decrease). Irrigation flow rate was 57 mL/min with an empty working channel. Flow was reduced by 50% and 68%, with the insertion of a 200 microm or 365 microm laser probe, respectively, and by 92.5% with a 3.2F basket. No damage to the image fiber occurred. The PolyScope optics system could identify a target of about 0.125 mm at a distance of 2 to 4 mm, based on 3 line pairs/mm needed for clear identification. Lithotripsy of renal calculi was performed for 40 stone burdens in 32 patients; the resulting stone-free rate was 87.5%. CONCLUSION: The novel semidisposable ureteroscope system PolyScope was simple to use, effective, and reliable in this preliminary clinical evaluation. It overcomes the inherent fragility of comparable devices, which renders the need for maintenance unnecessary. PMID- 20575700 TI - Effect of pulse energy, frequency and length on holmium:yttrium-aluminum-garnet laser fragmentation efficiency in non-floating artificial urinary calculi. AB - BACKGROUND AND PURPOSE: Holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy is the standard lithotrite in ureteroscopy. We investigated the influence of pulse frequency, energy and length on the fragmentation efficiency of Ho:YAG laser lithotripsy in non-floating artificial stones in vitro. MATERIALS AND METHODS: Stone fragmentation efficiency of three different Ho:YAG laser devices were evaluated in vitro at different pulse energy (1.0 and 2.0 J) and frequency settings (5 and 10 Hz), resulting in a standardized output power of 10W, respectively. Where possible, pulse length was modified (350 vs 700 microsec). Each setting was performed with a 273 microm and a 365 microm fiber. Lithotripsy was conducted using non-repulsive stones consisting of soft stone (plaster of Paris) and hard stone composition (Fujirock type 4). RESULTS: Our results showed an increased stone disintegration efficiency at higher pulse energy (2.0 J/5 Hz vs 1.0 J/10 Hz) independently of two fiber diameters and stone types applied in this study (P < 0.05 in 18 of 20 groups). Similarly, reduction of the pulse length from 700 to 350 microsec resulted in a higher stone disintegration (P < 0.05 in 13 of 16 groups). This effect was most prominent when applied to soft stones. Higher fiber diameter was not constantly associated with an increase in stone disintegration. CONCLUSION: We demonstrate that an increase of pulse energy and a reduction of pulse length at a standardized output power of 10W can improve Ho:YAG laser fragmentation efficiency in vitro in nonfloating stones. These results may potentially affect clinical practice of Ho:YAG laser lithotripsy in impacted or large stones, when retropulsion is excluded. PMID- 20575701 TI - Prospects in percutaneous ablative targeting: comparison of a computer-assisted navigation system and the AcuBot Robotic System. AB - AIM: Precise targeting is essential for adequate treatment of lesions during image-guided therapy. The aim of this study was to compare the performance of two emerging image-guided targeting technologies in a phantom model. MATERIALS AND METHODS: A computer-assisted navigation system and AcuBot were tested using three operators: an interventional radiologist and two endourologists. Fiducials were placed in an anatomic gelatin phantom and targeted by both systems. The images were reconstructed and analyzed using a specialized software package (Amira; Visage Imaging, Carlsbad, CA). Accuracy was assessed by measuring proximity of the tip of the needle to the fiducial on computed-tomography-guided imaging. Accuracy and time to target were quantified and compared. RESULTS: The mean distance from the desired target for AcuBot was 1.2 mm (range: 0.39-2.82). The mean distance from the desired target for the navigation system was 5.8 mm (range: 1.8-11.9). The AcuBot was significantly more accurate than the navigation system (p < 0.0001). The mean time from target acquisition to needle placement was 37 seconds (range: 15-75) for the AcuBot and 108 seconds (range: 45-315) for the navigation system (p = 0.001). CONCLUSION: Emerging technologies hold promise for increased accuracy during percutaneous targeted procedures. Both the AcuBot and the computer-assisted navigation system were accurate and efficient in a phantom targeting model. AcuBot was significantly more accurate, faster, and less user dependent than the navigation system. Further studies in animal and clinical studies are warranted to further advance this promising technology. PMID- 20575702 TI - Acupuncture treatment for persistent hiccups in patients with cancer. AB - OBJECTIVE: The objective of this study was to investigate the effects of acupuncture treatment for persistent hiccups in cancer patients. DESIGN: The study design was a retrospective case series. SETTINGS/LOCATION: The study setting was the Clinical Research Center of the National Institutes of Health. SUBJECTS: The subjects were 16 adult male patients ages 27-71 with cancer, with persistent hiccups. INTERVENTIONS: There were one to three acupuncture sessions over a 1-7-day period. OUTCOME MEASURES: Treatment efficacy was measured using a hiccup assessment instrument pre- and post-treatment. The effects of acupuncture on common symptoms reported by all patients were also evaluated. RESULTS: Thirteen (13) patients experienced complete remission of persistent hiccups (p < 0.0001); 3 patients experienced decreased hiccups severity. Significant improvement was observed in discomfort (p < 0.0001), distress (p < 0.0001), and fatigue (p = 0.0078). CONCLUSIONS: This case series demonstrates that acupuncture may be a clinically useful, safe, and low-cost therapy for persistent hiccups in patients with cancer. PMID- 20575703 TI - Provider support in complementary and alternative medicine: exploring the role of patient empowerment. AB - BACKGROUND: The quality of the patient-provider relationship is well-recognized as having a key role in therapeutic outcomes irrespective of treatment effects. Yet there is a lack of scales to assess aspects of complementary and alternative medicine (CAM) provider support. OBJECTIVES: The objectives of this study were to develop and psychometrically evaluate scales to measure patients' perceptions of provider support, patient-centered care, and empowerment as predictors of health outcomes. METHODS: Based on five focus groups with CAM clients, we developed the following three scales: Perceived Provider Support, Patient-Centered Care (PCC), and Empowerment. The scales were cognitively tested with 6 CAM users and then pilot-tested with 216 respondents. Confirmatory factor analyses, item response theory analyses, and Cronbach's alphas were conducted to evaluate their psychometric properties. Bootstrapping techniques and structural equation modeling were used to evaluate Empowerment as a mediator of the relationship of Perceived Provider Support and PCC with symptom relief. RESULTS: All three scales demonstrated high internal consistency with Cronbach's alphas of 0.85 to 0.90 and confirmatory factor analyses supported a one-factor solution for each scale. Controlling for demographics, presenting problem, and main CAM provider used in the past 12 months, each of the scales had a positive and significant relationship with overall symptom relief for the patient's primary presenting problem (p < .01). Bootstrapped Sobel tests were significant (p < .01), supporting the role of empowerment as a mediator of the impact of PCC and provider support on symptom relief. A structural equation model combining PCC and provider support into a single latent variable representing quality of patient provider interactions and including empowerment as a mediator fit well. CONCLUSIONS: From a holistic perspective, CAM treatment effects can arise in part from sources related to the therapeutic relationship, as well as the philosophy of healing and specific techniques designed to reduce symptoms. This analysis provides conceptual support for this perspective, a means to evaluate aspects of the therapeutic relationship and to measure its impact on outcomes of CAM treatment across conditions and therapies. PMID- 20575704 TI - Role of prophylactic antibiotics in laparoscopic cholecystectomy and risk factors for surgical site infection: a randomized controlled trial. AB - BACKGROUND: The aim of this clinical trial was to determine whether prophylactic antibiotics could prevent surgical site infection (SSI) after laparoscopic cholecystectomy and to identify any risk factors for infection. METHODS: The study included 100 patients undergoing laparoscopic cholecystectomy. They were randomized to receive either a single dose of ceftriaxone (Group A; n = 50) or physiologic saline as placebo (Group B; n = 50) after the induction of anesthesia. Patient demographics and clinical and surgical outcomes were recorded. RESULTS: The incidence of SSI was similar in the two groups: 2 patients in group A and 4 patients in group B (chi(2) = 0.71; p = 0.40). None of the factors studied was associated with surgical site infection statistically, as shown by binary logistic regression analysis. CONCLUSION: A single dose of prophylactic antibiotic failed to decrease the likelihood of SSI after laparoscopic cholecystectomy. PMID- 20575707 TI - Identifying specific cues and contexts related to smoking craving for the development of effective virtual environments. AB - Craving is considered the main variable associated with relapse after smoking cessation. Cue Exposure Therapy (CET) consists of controlled and repeated exposure to drug-related cues with the aim of extinguishing craving responses. Some virtual reality (VR) environments, such as virtual bars or parties, have previously shown their efficacy as tools for eliciting smoking craving. However, in order to adapt this technology to smoking cessation interventions, there is a need for more diverse environments that enhance the probability of generalization of extinction in real life. The main objective of this study was to identify frequent situations that produce smoking craving, as well as detecting specific craving cues in those contexts. Participants were 154 smokers who responded to an ad hoc self-administered inventory for assessing craving level in 12 different situations. Results showed that having a drink in a bar/pub at night, after having lunch/dinner in a restaurant and having a coffee in a cafe or after lunch/dinner at home were reported as the most craving-inducing scenarios. Some differences were found with regard to participants' gender, age, and number of cigarettes smoked per day. Females, younger people, and heavier smokers reported higher levels of craving in most situations. In general, the most widely cited specific cues across the contexts were people smoking, having a coffee, being with friends, and having finished eating. These results are discussed with a view to their consideration in the design of valid and reliable VR environments that could be used in the treatment of nicotine addicts who wish to give up smoking. PMID- 20575708 TI - Commonalities in the psychological factors associated with problem gambling and Internet dependence. AB - The most commonly applied conceptual approach for excessive Internet use has been as a behavioral addiction, similar to pathological or problem gambling. In order to contribute to the understanding of Internet dependence as a disorder resembling problem gambling, the current study aimed to examine the relationship between problem gambling and Internet dependence and the degree to which psychological factors associated with problem gambling are relevant to the study of Internet dependence. The factors of depression, anxiety, student stressors, loneliness, and social support were examined in a sample of university students from several Australian universities. The findings revealed that there is no overlap between the populations reporting problem gambling and Internet dependence, but that individuals with these disorders report similar psychological profiles. Although requiring replication with larger community samples and longitudinal designs, these preliminary findings suggest that problem gambling and Internet dependence may be separate disorders with common underlying etiologies or consequences. The implications of the findings in relation to the conceptualization and management of these disorders are briefly discussed. PMID- 20575710 TI - Effects of intimate partner violence on pregnancy trauma and placental abruption. AB - AIMS: Intimate partner violence (IPV) during pregnancy increases women's risk of pregnancy complications and adverse birth outcomes. The goal of this study was to examine the association between IPV and prenatal trauma and placental abruption during pregnancy. METHODS: Prenatal and hospital obstetrical charts were reviewed for 2873 women who gave birth between January 2000 and March 2002 in a Northeastern city. We examined associations among sociodemographic characteristics, health-related variables, IPV, and pregnancy trauma and placental abruption using univariate and multivariate logistic regression. RESULTS: Of the 2873 women in the analyses, 105 (3.7%) reported IPV during prenatal care. After controlling for sociodemographic variables; tobacco, alcohol, and drug use; preeclampsia; and gestational diabetes during pregnancy, women who reported IPV also had higher odds of pregnancy trauma and placental abruption (adjusted odds ratio [OR] 32.08, 95% confidence interval [CI] 14.33 71.80, p < 0.01, and OR 5.17, 95% CI 1.37-19.51, p < 0.05, respectively). CONCLUSIONS: This study found that IPV is a significant and independent risk factor for pregnancy trauma and placental abruption after controlling for factors typically associated with these outcomes. This study has implications for partner violence screening and intervention policies among pregnant women and highlights the importance of making distinctions about the type of IPV that women experience. PMID- 20575712 TI - Carraguard acceptability among men and women in a couples study in Thailand. AB - OBJECTIVE: The aim of this study is to evaluate the use and acceptability of Carraguard among men and women enrolled as couples in a microbicide trial. MATERIALS AND METHODS: Focus groups were conducted with participants in a 6-month randomized, placebo-controlled trial that enrolled sexually active, low-risk couples in Thailand. Participants were blinded as to which gel they had received at the time of the discussions. RESULTS: Most men and women liked the gel and found it acceptable. The majority of men and women thought that using the gel increased sexual pleasure, although participants disagreed about whether using the gel increased sexual frequency. Drawbacks of gel use included that it was too wet or messy, and nearly all respondents thought that the applicator was too hard. Most men and women questioned the utility of using the gel among married couples since gel use was tied to perception of HIV/STI risk. However, those who perceived themselves to be at risk expressed interest in using the product as an alternative to condoms. Many women were particularly interested in a product that also had contraceptive properties. Gel use also raised issues of trust and fidelity among couples and questions about men's ability to detect women's use of the product. CONCLUSION: Men and women in this study found the gel acceptable and thought that it should be made available if it is found to be safe and effective. Strategies for marketing a potential microbicide product must take the target population into consideration. For married couples, key considerations may be partner dynamics and trust issues, whereas messages focusing on sexual pleasure or disease prevention may resonate more strongly with sex workers or other populations. PMID- 20575711 TI - Mammographic breast density and tolerance for short-term postmenopausal hormone therapy suspension. AB - BACKGROUND: Breast density tends to decrease when women stop taking hormone therapy (HT). Some women find HT cessation difficult to tolerate, possibly because of fluctuations in endogenous hormone levels and vasomotor symptoms. We hypothesized that women with dense breasts might have lower tolerance for short term HT suspension than do women with fatty breasts. METHODS: As part of the Radiologic Evaluation And breast Density (READ) trial, we randomly assigned 881 women aged 45-80 with a prior screening (index) mammogram to suspend HT for 1 or 2 months before their next screening (study) mammogram. We measured continuous breast density on index mammograms using computer-assisted thresholding. At study mammograms, women indicated tolerance for stopping HT from 1 (extremely difficult) to 7 (very easy). Using linear regression, we evaluated the association between index breast density and tolerance after cessation, adjusting for age, body mass index (BMI), HT type, randomization group, and vasomotor symptoms. RESULTS: A higher percentage of breast density was associated with lower unadjusted mean tolerance scores (tolerance 4.27, 95% confidence interval [CI] 3.77-4.77 for women with > or =50% density, and 4.73, 95% CI 4.45-5.01 for women with <10% density, not a statistically significant difference). In adjusted analyses, neither percent breast density nor dense breast area was associated with tolerance for HT suspension. CONCLUSIONS: Although HT use affects breast density, tolerance for suspending HT is not associated with breast density. Women with dense breasts have the greatest potential for decreases in density after HT cessation; they should tolerate stopping HT as well as women with fatty breasts. PMID- 20575713 TI - Do breastfeeding intentions of pregnant inner-city teens and adult women differ? AB - OBJECTIVE: This study compared the breastfeeding intentions and attitudes of pregnant low-income inner-city teens (age <=19 years) and non-teens (age >=20) to determine if age is a significant determinant of intent to breastfeed in this population. PATIENTS AND METHODS: We used structured interviews to examine the feeding intentions and attitudes of consecutive healthy pregnant women receiving obstetrical care at the Women's Health Center, MacDonald Women's Hospital, Cleveland, OH (June 1-July 31, 2007). The primary outcome measure was rate of intent to breastfeed among teen versus non-teen participants. Attitudes and self assessed knowledge regarding breastfeeding were compared between teens and non teens, and multiple logistic regression analysis was used to examine the effect of age on breastfeeding intent. RESULTS: We interviewed 176 pregnant women (95% African-American, 94% single marital status, median age 22 years [range, 15-41 years], 46 [26%] teens) at a median of 27 weeks of pregnancy. There were no significant differences between teens and non-teens in race, marital status, or timing of first prenatal visit or interview. Rate of intent to breastfeed and planned duration and exclusivity of breastfeeding, as well as most measured attitudes about breastfeeding including "back to work" plans, were not significantly different between groups. Significant determinants of feeding intent included primiparity, good self-assessed knowledge about breastfeeding, and having support from the father of the baby. CONCLUSIONS: In a population at high risk for choosing not to breastfeed, we found no significant explanatory effect of age on breastfeeding intention, implying that an inclusive targeted breastfeeding intervention program may be effective for both teens and non-teens in a low-income inner-city population. We also found that the support of the father of the baby significantly influenced breastfeeding intent among our participants, suggesting that paternal involvement will be integral to the success of breastfeeding. PMID- 20575714 TI - Breastfeeding intentions of female physicians. AB - BACKGROUND: It is known that physician mothers' breastfeeding behavior impacts their anticipatory guidance to their patients, which in turn influences patients' breastfeeding initiation and continuation. Therefore, studying physician mothers' breastfeeding behavior is important, as it impacts not only the well-being of themselves and their families, but eventually the well-being of their patients and patients' families. However, previous studies of breastfeeding among physician mothers in the United States have not explored their breastfeeding intentions. We therefore sought to explore infant feeding intentions of physician mothers. METHODS: We report data gathered from 50 physician volunteers, mainly affiliated with Johns Hopkins University (Baltimore, MD), using a questionnaire. RESULTS: Consistent with previous physician studies, we found high breastfeeding initiation rates among our participants. However, the breastfeeding continuation rates of mothers in our study at 6 and 12 months were higher than those reported in previous physician studies. Our data showed that while physician mothers intended to breastfeed 64% of the infants for at least 12 months and while 97% of infants were breastfed at birth, only 41% continued to receive breastmilk at 12 months. This discrepancy suggests that work-related factors may influence physician mothers' breastfeeding behavior and might have a larger impact than these mothers' education and intentions on breastfeeding duration. CONCLUSION: This finding supports implementing workplace strategies and programs to promote breastfeeding duration among physician mothers returning to work. PMID- 20575715 TI - Torun. PMID- 20575716 TI - What a transformation-ATA at fifteen! PMID- 20575718 TI - MassGeneral Hospital for Children: connecting at-home attending physicians to pediatric patients. PMID- 20575719 TI - NASA, telemedicine, and endotronix: how NASA's research led to the creation of a cutting-edge telemedicine company. PMID- 20575720 TI - Telemedicine in urban and suburban childcare and elementary schools lightens family burdens. AB - BACKGROUND: Acute illness challenges all families with young children. The Health e-Access Telemedicine Network in Rochester, NY, has enabled >7,000 telemedicine visits since 2001 among children in childcare or elementary schools, predominantly from Rochester's inner city. Large reductions in illness-related absence and emergency department use among Health-e-Access participants have occurred. OBJECTIVE: The study was aimed to assess parent perception of telemedicine as a means to reduce burdens associated with childhood illness. DESIGN/METHODS: A total of 800 parents were surveyed before (578) or after (318) a child had at least one Health-e-Access visit. Queries addressed access to healthcare, conflicts between work/school and child's care during illness, and concerns and likes about telemedicine. Perceptions were elicited through open ended and direct queries. RESULTS: Among all respondents, 16% had high-school education and 25% had a college education. Race/ethnicity of the respondents included black (43.6%), Hispanic (22.9%), white (30.0%), and other (3.5%). All identified a primary care practice as a source for well childcare. Most (58%) had given antipyretics to their child to avoid being called by childcare or elementary school staff about illness. Likert scale interview items addressing quality of care elicited low levels of worry or concern. Worry scores trended lower after experience. Among 532 comments about Health-e-Access elicited through open-ended probes, positive ones (likes) predominated (84.6%). Likes most commonly included convenience/time saved (33.6% of all comments), parent stayed at work (13.5%), drug delivered to child site (7.1%) or called ahead to pharmacy (4.9%), and confidence in care (2.3%). Negative responses (concerns) totaled 15.4% of comments and most commonly included reliability of diagnosis (2.6%), technical problems (1.3%), and preference for in-person care (0.8%). CONCLUSIONS: Health-e-Access was well accepted by a substantial, diverse group of parents despite unfamiliarity with this approach to care. Convenience and convenience related experience dominated perceptions. This model enables service beyond that mandated by payers and beyond that generally provided by medical practices. PMID- 20575722 TI - The impact of telehealth on wait time for ENT specialty care. AB - Audiology in rural Alaska has changed dramatically in the past 6 years by integrating store and forward telemedicine into routine practice. The Audiology Department at the Norton Sound Health Corporation in rural Nome Alaska has used store-and-forward telemedicine since 2002. Between 2002 and 2007, over 3,000 direct audiology consultations with the Ear, Nose, and Throat (ENT) Department at the Alaska Native Medical Center in Anchorage were completed. This study is a 16 year retrospective analysis of ENT specialty clinic wait times on all new patient referrals made by the Norton Sound Health Corporation providers before (1992 2001) and after the initiation of telemedicine (2002-2007). Prior to use of telemedicine by audiology and ENT, 47% of new patient referrals would wait 5 months or longer to obtain an in-person ENT appointment; this dropped to 8% of all patients in the first 3 years with telemedicine and then less than 3% of all patients in next 3 years using telemedicine. The average wait time during the first 3 years using telemedicine was 2.9 months, a 31% drop compared with the average wait time of 4.2 months for the preceding years without telemedicine. The wait time then dropped to an average of 2.1 months during the next 3 years of telemedicine, a further drop of 28% compared with the first 3 years of telemedicine usage. PMID- 20575721 TI - Telephone-based psychiatric referral-care management intervention health outcomes. AB - OBJECTIVE: This study examined the effectiveness of a telephone-based referral care management (TBR-CM) intervention on psychiatric health outcomes. MATERIALS AND METHODS: Between September 2005 and May 2006, primary care patients (n = 169) at the Philadelphia Veterans Affairs Medical Center completed a psychiatric interview over the telephone, of which 113 gave consent and were randomized into the TBR-CM usual care or intervention groups (n = 40 [39%] depression, n = 40 [39%] substance abuse, and n = 33 [22%] comorbid condition: depression and substance abuse). Usual care consisted of participants receiving a psychiatric appointment, followed up with standard institutional reminders. The intervention care group received the same, with the addition of brief motivational telephone sessions. Baseline and 6-month interviews were used to obtain study data. RESULTS: Results indicated that there was improvement in mental health functioning (p < 0.0001), depression (p < 0.0001), and binge (p < 0.0332) outcomes over the 6-month interview (78% retention). However, there was no change observed for physical health functioning and drinks per week outcomes. For mental health functioning, depression, and binge rates there were no randomization group assignment effects, indicating that the intervention care group did not show better health outcomes despite showing higher levels of psychiatric appointment attendance. CONCLUSIONS: Patients who are exposed to the intervention have similar health outcomes as patients in usual care. In conclusion, the TBR-CM intervention does not lead to relatively improved psychiatric health outcomes. Further research is necessary to examine the efforts needed to extend increased treatment engagement into improved health outcomes for intervention recipients. PMID- 20575723 TI - Hearing assessment-reliability, accuracy, and efficiency of automated audiometry. AB - OBJECTIVE: This study investigated the reliability, accuracy, and time efficiency of automated hearing assessment using a computer-based telemedicine-compliant audiometer. MATERIALS AND METHODS: Thirty normal-hearing subjects and eight hearing-impaired subjects were tested with pure-tone air conduction audiometry (125-8,000 Hz) in a manual and automated configuration in a counterbalanced manner. For the normal-hearing group each test was repeated to determine test retest reliability and recording time, and preference for threshold-seeking method (manual vs. automated) was documented. RESULTS: Test-retest thresholds were not significantly different for manual and automated testing. Manual audiometry test-retest correspondence was 5 dB or less in 88% of thresholds compared to 91% for automated audiometry. Thresholds for automated audiometry did not differ significantly from manual audiometry with 87% of thresholds in the normal-hearing group and 97% in the hearing-impaired group, corresponding within 5 dB or less of each other. The largest overall average absolute difference across frequencies was 3.6 +/- 3.9 dB for the normal-hearing group and 3.3 +/- 2.4 for the hearing-impaired group. Both techniques were equally time efficient in the normal-hearing population, and 63% of subjects preferred the automated threshold-seeking method. CONCLUSIONS: Automated audiometry provides reliable, accurate, and time-efficient hearing assessments for normal-hearing and hearing impaired adults. Combined with an asynchronous telehealth model it holds significant potential for reaching underserved areas where hearing health professionals are unavailable. PMID- 20575724 TI - Assessment of children's literacy via an Internet-based telehealth system. AB - OBJECTIVE: Interactive telehealth applications have potential for the assessment of reading disability in school-aged children. However, there is currently a lack of research on the validity of such applications. The aim of this study was to investigate the validity and reliability of an Internet-based videoconferencing system for the assessment of children's literacy on a battery of standardized assessments. MATERIALS AND METHODS: Twenty children aged 8-13 years were simultaneously assessed in real-time both face-to-face and over a 128-Kbps Internet link. The assessments included eight subtests of the Queensland University Inventory of Literacy (QUIL), the South Australian Spelling Test, and the Neale Analysis of Reading Ability, 3rd edition (Neale-3). RESULTS: The limits of agreement for the majority of raw scores fell within predetermined clinical criteria, with the exception of the QUIL nonword reading and nonword spelling measures and the rate score of the Neale-3. Weighted kappa analyses on the tests' scaled scores indicated very good agreement for all parameters (kappa 0.92-1.00). Percentage levels of agreement were adequate (above 80%) for most measures except for the nonword reading raw score of the QUIL and the reading error classification component of the Neale-3. Very good intra- and interrater reliability was determined for all online parameters (intraclass correlation coefficient 0.98-1.00). CONCLUSIONS: As issues with audio latency, break-up, and echo were observed, some modifications to the technology may improve system effectiveness and usability. However, the overall positive results of this study support the validity and reliability of the assessment of children's literacy skills via telehealth. PMID- 20575725 TI - Exploring the translational impact of a home telemonitoring intervention using time-motion study. AB - OBJECTIVE: Home telemonitoring improves clinical outcomes but can generate large amounts of data. Automating data surveillance with clinical decision support could reduce the impact of translating these systems to clinical settings. We utilized time-motion methodology to measure the time spent on activities monitoring subjects in the two groups of a home spirometry telemonitoring randomized controlled trial: the manual nurse review (control) group and the automated review (intervention) group. These results are examined for potential workflow effects that could occur when the intervention translates to a clinical setting. MATERIALS AND METHODS: Time motion is an established industrial engineering technique used to evaluate workflow by measuring the time of predefined, discrete tasks. Data were collected via direct observation of two research nurses by a single observer using the repetitive or snap-back timing method. All observed tasks were coded using a list of work activities defined and validated in an earlier study. Reliability data were collected during a 2-h session with a secondary observer. RESULTS: Reliability of the primary observer was established. During 35 h of data collection, a sample of 938 task observations were recorded and coded using 46 previously defined and 5 newly defined work activities. Between-group comparisons of activity time for subjects in the two study groups showed significantly more time spent on data review activities for the automated review group. Reclassification of the 51 observed activities identified 15 activities that would translate to a clinical setting, of which 5 represent potentially new activities. CONCLUSIONS: Implementing an intervention into a clinical setting could add work activities to the clinical workflow. Time-motion study of research personnel working with new clinical interventions provides a template for evaluating the workflow impact of these interventions prior to translation from a research to a clinical setting. PMID- 20575726 TI - The diagnostic accuracy of telerehabilitation for nonarticular lower-limb musculoskeletal disorders. AB - OBJECTIVE: Musculoskeletal conditions are highly prevalent and disabling, particularly in rural and remote areas. In these areas, access to rehabilitation services is limited by the availability of physical therapists. Telerehabilitation may be a feasible solution to the issue of rural physical therapy service access; however, there is little existing evidence for clinical efficacy. The aim of this study was to establish the criterion validity and reliability of remote physical assessment and diagnosis of nonarticular lower limb musculoskeletal conditions via telerehabilitation. MATERIALS AND METHODS: Nineteen participants with existing nonarticular lower limb musculoskeletal conditions were assessed by a face-to-face therapist and a remote therapist to establish criterion validity of telerehabilitation. Video recordings from the telerehabilitation session were reviewed after 1 month by the remote therapist to establish intrarater reliability and by a second remote therapist to establish interrater reliability. Patho-anatomical diagnoses, system diagnoses, and the findings of the physical examination were compared statistically. RESULTS: There was 79% or higher primary diagnosis agreement (same or similar diagnoses) and 79% or higher exact system diagnosis agreement for validity, intrarater reliability, and interrater reliability studies. The physical examination findings showed substantial agreement (0.61 < kappa < 0.80) in the validity study and almost perfect agreement (0.81 < kappa < 1.00) in the intrarater and interrater reliability studies. CONCLUSIONS: Using telerehabilitation for musculoskeletal physical therapy assessment of nonarticular lower limb conditions was found to be valid and reliable. Existing diagnostic reasoning can be applied; however, new methods of patient self-examination are needed to enable differential diagnosis. PMID- 20575727 TI - Do diabetic veterans use the Internet? Self-reported usage, skills, and interest in using My HealtheVet Web portal. AB - OBJECTIVE: The Veterans Health Administration has developed My HealtheVet (MHV), a Web-based portal that links veterans to their care in the veteran affairs (VA) system. The objective of this study was to measure diabetic veterans' access to and use of the Internet, and their interest in using MHV to help manage their diabetes. MATERIALS AND METHODS: Cross-sectional mailed survey of 201 patients with type 2 diabetes and hemoglobin A(1c) > 8.0% receiving primary care at any of five primary care clinic sites affiliated with a VA tertiary care facility. Main measures included Internet usage, access, and attitudes; computer skills; interest in using the Internet; awareness of and attitudes toward MHV; demographics; and socioeconomic status. RESULTS: A majority of respondents reported having access to the Internet at home. Nearly half of all respondents had searched online for information about diabetes, including some who did not have home Internet access. More than a third obtained "some" or "a lot" of their health-related information online. Forty-one percent reported being "very interested" in using MHV to help track their home blood glucose readings, a third of whom did not have home Internet access. Factors associated with being "very interested" were as follows: having access to the Internet at home (p < 0.001), "a lot/some" trust in the Internet as a source of health information (p = 0.002), lower age (p = 0.03), and some college (p = 0.04). Neither race (p = 0.44) nor income (p = 0.25) was significantly associated with interest in MHV. CONCLUSIONS: This study found that a diverse sample of older VA patients with sub-optimally controlled diabetes had a level of familiarity with and access to the Internet comparable to an age-matched national sample. In addition, there was a high degree of interest in using the Internet to help manage their diabetes. PMID- 20575728 TI - Remote health monitoring using mobile phones and Web services. AB - Diabetes and hypertension have become very common perhaps because of increasingly busy lifestyles, unhealthy eating habits, and a highly competitive workplace. The rapid advancement of mobile communication technologies offers innumerable opportunities for the development of software and hardware applications for remote monitoring of such chronic diseases. This study describes a remote health monitoring service that provides an end-to-end solution, that is, (1) it collects blood pressure readings from the patient through a mobile phone; (2) it provides these data to doctors through a Web interface; and (3) it enables doctors to manage the chronic condition by providing feedback to the patients remotely. This article also aims at understanding the requirements and expectations of doctors and hospitals from such a remote health-monitoring service. PMID- 20575729 TI - Attitudes and reactions to a healthcare robot. AB - OBJECTIVE: The use of robots in healthcare is a new concept. The public's perception and acceptance is not well understood. The objective was to investigate the perceptions and emotions toward the utilization of healthcare robots among individuals over 40 years of age, investigate factors contributing to acceptance, and evaluate differences in blood pressure checks taken by a robot and a medical student. MATERIALS AND METHODS: Fifty-seven (n = 57) adults aged over 40 years and recruited from local general practitioner or gerontology group lists participated in two cross-sectional studies. The first was an open-ended questionnaire assessing perceptions of robots. In the second study, participants had their blood pressure taken by a medical student and by a robot. Patient comfort with each encounter, perceived accuracy of each measurement, and the quality of the patient interaction were studied in each case. Readings were compared by independent t-tests and regression analyses were conducted to predict quality ratings. RESULTS: Participants' perceptions about robots were influenced by their prior exposure to robots in literature or entertainment media. Participants saw many benefits and applications for healthcare robots, including simple medical procedures and physical assistance, but had some concerns about reliability, safety, and the loss of personal care. Blood pressure readings did not differ between the medical student and robot, but participants felt more comfortable with the medical student and saw the robot as less accurate. Although age and sex were not significant predictors, individuals who held more positive initial attitudes and emotions toward robots rated the robot interaction more favorably. CONCLUSIONS: Many people see robots as having benefits and applications in healthcare but some have concerns. Individual attitudes and emotions regarding robots in general are likely to influence future acceptance of their introduction into healthcare processes. PMID- 20575730 TI - Exploring perceptions of healthcare professionals in the implementation of a new professional role of clinical telehealth coordinator within a university integrated healthcare network. AB - OBJECTIVE: As telehealth networks develop across Canada, new professional roles start to emerge. A university healthcare center part of an integrated health network has identified the need to introduce a clinical coordinator for specialized telehealth programs. However, very little is found in the current literature about the description or core competencies that such a professional should possess as well as the ways to implement this role. The objective of this study was to explore how healthcare professionals (HCPs) involved in a specialized teleoncology program perceive a new clinical telehealth coordinator (CTC) role within a university integrated healthcare network (UIHN) in a metropolitan area in Quebec, Canada. MATERIALS AND METHODS: A descriptive qualitative design was used and a purposive sample of nine HCPs, including physicians, nurses, and pharmacists who were members of a UIHN teleoncology committee, was recruited. RESULTS: The HCPs identified that the CTC was a multifaceted role. The core competencies identified by the HCPs included knowledge, expertise, and experience. Participants identified three key factors in the implementation of this role, namely, the structural support, having a common language, and making the implementation of this role relevant. CONCLUSIONS: The results suggest that this CTC role may be more complex than originally expected and that the diverse competencies suggest an expanded nature to this role. This has important implications for administrative strategies when addressing the key factors in the implementation of this role. PMID- 20575731 TI - Efficiency in the transmission of information through digital imaging and communications in medicine using security mechanisms: tests with DISCUS. AB - This article describes our experience in using a Picture Archiving and Communications System, known as Secure Medical Image Information System, based on the Digital Imaging and Communications in Medicine standard that supports the use of secure transmissions, from the point of view of how the use of secure sending methods has an effect on the efficiency in the transmission according to the network employed, to quantify productivity loss due to the encryption, the secure transmission, and the subsequent decryption. To test the Secure Medical Image Information System, a series of medical data transmission were conducted from A Coruna (Spain) to the Virgen de las Nieves Hospital, situated 1,000 km away, in Granada (Spain). Once we studied the networking infrastructure of the hospital and its available image generation devices, we subsequently carried out a series of measurements during the transmissions, which allowed us to analyze the behavior of the system with different network schemes and connection speeds. The results obtained from these investigations demonstrate that the impact of secure data-sending methods on the productivity of the system is higher in networks whose capacities are higher and it is not affected by sending data during different periods in the day. In this regard, the presented approach may serve as a model for other small, and possibly mid-sized, medical centers. PMID- 20575732 TI - University of Texas Medical Branch telemedicine disaster response and recovery: lessons learned from hurricane Ike. AB - Despite previous efforts and expenditure of tremendous resources on creating and simulating disaster response scenarios, true disaster response, specifically for healthcare, has been inadequate. In addition, none of the >200 local and statewide telemedicine programs in the United States has ever responded to a large-scale disaster, let alone, experienced one directly. Based on its experience with hurricanes Rita and, most recently, Ike, the University of Texas Medical Branch (UTMB) experienced its most challenging trials. Although there were significant disruptions to a majority of UTMB's physical and operational infrastructures, its telemedicine services were able to resume near normal activities within the first week of the post-Ike recovery period, an unimaginable feat in the face of such remarkable devastation. This was primarily due in part to the flexibility of its data network, the rapid response, and plasticity of its telemedicine program. UTMB's experiences in providing rapid and effective medical services in the face of such a disaster offer valuable lessons for local, state, and national disaster preparations, policy, and remote medical delivery models and programs. PMID- 20575733 TI - Development and recent achievements of telemedicine in china. AB - Although China started to study and implement telemedicine much later than other advanced countries, telemedicine is developing very fast in this country. Research on telemedicine is also getting popular, and more and more teleconsultant systems are being carried out. For the purpose of assessing the development of telemedicine in China over these past 50 years, we conducted a study of three elements, namely (1) teleconsultations, (2) academic activities, and (3) education. We carried out our study from three perspectives: the teleconsultant, telemedicine academic activities, and telemedicine education. In this article, we also show our recent achievement in telemedicine based on the Regional Collaborative Medical Service. PMID- 20575734 TI - Planning for Internet connectivity in remote patient monitoring. AB - It is important for healthcare organizations to understand the requirements and challenges of logistics when deploying remote patient monitoring (RPM) technologies in patient homes. Although most organizations prepare thoroughly for the clinical and work flow aspect of RPM solutions, they neglect to consider the logistical resources necessary to successfully manage a broad deployment. The term "logistics" in this context refers to the processes and infrastructure required to enable the use of RPM technologies in the patient's home. This article has been generated from the findings and observations of several studies where logistical objectives were included in the protocol in addition to the conventional metrics of clinical outcome, satisfaction, and economic measures. These studies implemented several high-speed Internet connectivity models with the use of wired broadband, 3G wireless, or a combination. The organizations that utilized 3G to provide Internet connectivity experienced significantly fewer logistical issues and patient frustration. It was also observed that regardless of the model, each of the clinical partners in these studies were not adequately prepared to manage Internet connectivity. Because of this, all experienced some level of difficulty installing and supporting RPM devices in the home. PMID- 20575736 TI - Reflections on providing sport science support for athletes with learning difficulties. AB - PURPOSE: To highlight the benefits and the need for sport science support for athletes with learning difficulties, and to reflect on our experience of working with the GB squad for athletes with learning difficulties. METHODS: A review of key and relevant literature is presented, followed by a discussion of the sport science support provision and the issues that emerged in working with athletes with learning difficulties. Pre- and post- physiological tests along with evaluations of athletes' potential to benefit from sport psychology support were conducted. The aim of these tests was to provide information for the athletes and the coaches on fitness levels, to use this information to plan future training, and to identify how well the performance could be enhanced. RESULTS: A case study is presented for one athlete, who had competed in distance events. The focus is the psychological support that was provided. CONCLUSIONS: It is clear that athletes with learning difficulties require the same type of sports science support as their mainstream peers. However, sport scientists will need to consider ways to extend their practice in order to provide the appropriate level of support. PMID- 20575737 TI - Foot morphology and substrate adhesion in the Madagascan hissing cockroach, Gromphadorhina portentosa. AB - Insects are successful terrestrial organisms able to locomote over a wide range of obstacles and substrates. This study investigated how foot morphology (tarsal structure) correlates with substrate adhesion and ecological niche in the Madagascan hissing cockroach, Gromphadorhina portentosa Schaum (Blattaria: Blaberidae). Using light and scanning electron microscopy, the morphology of the different structures of the tarsus of G. portentosa was analysed. Using an Instron universal testing machine, a series of peak force experiments were then conducted to record the force required to lift the cockroaches off different substrates. G. portentosa was pulled off 10 different substrates, which consisted of smooth Perspex; Perspex scored at 1cm intervals; Perspex hatched at 1 cm, 0.5 cm, and 1 mm intervals; Perspex abraded with fine grade sandpaper; Perspex abraded with coarse grade sandpaper; wood; glass; and Teflon. A clear relationship was seen where an increase in scoring on the Perspex caused a decrease in adhesive ability of G. portentosa. This may be due to there being adequate contact area for the attachment of the pads and to allow the claws to engage. The results obtained suggest that to achieve the greatest adhesion to substrates, G. portentosa uses a combined effect of both adhesive pads and pretarsal claws. Adhesion to a wide range of substrates appears to be an adaptation to life as a wingless forest floor dweller. PMID- 20575738 TI - Parachuting behavior and predation by ants in the nettle caterpillar, Scopelodes contracta. AB - This paper documents the bizarre descending behavior from the tree crown to the ground of the larvae of the moth, Scopelodes contracta Walker (Lepidoptera: Limacodidae) and the interaction of the larva with predatory ants. S. contracta larvae infest leaves of many tree species in urban areas and orchards in Japan. Mature larvae and leaves without basal leaf parts were found under trees of four species infested with S. contracta larvae in Osaka, Japan. Individual larvae riding on leaves were observed falling from tree crowns to the ground. Many S. contracta cocoons were found in the soil below the trees two weeks after the observed parachuting. These observations indicate that S. contracta larvae parachuted to the ground where they spin their cocoons in the soil. When a larva that had just parachuted down was returned to an arboreal twig, the larva repeated the parachuting behavior. This parachuting behavior appears to be adaptive, because larvae can descend to the ground safely and with low energy cost. Worker ants of Tetramorium tsushimae Emery (Hymenoptera: Formicidae) and Pristomyrmex punctatus Mayr (Hymenoptera: Formicidae) occasionally attacked larvae on the ground before they had a chance to burrow in the soil. PMID- 20575739 TI - Characterization of the earwig, Doru lineare, as a predator of larvae of the fall armyworm, Spodoptera frugiperda: a functional response study. AB - Spodoptera frugiperda Smith (Lepidoptera: Noctuidae) is considered as the most important pest of maize in almost all tropical America. In Argentina, the earwig Doru lineare Eschscholtz (Dermaptera: Forficulidae) has been observed preying on S. frugiperda egg masses in corn crops, but no data about its potential role as a biocontrol agent of this pest have been provided. The predation efficiency of D. lineare on newly emerged S. frugiperda larva was evaluated through a laboratory functional response study. D. lineare showed type II functional response to S. frugiperda larval density, and disc equation estimations of searching efficiency and handling time were (a) = 0.374 and (t) = 182.9 s, respectively. Earwig satiation occurred at 39.4 S. frugiperda larvae. PMID- 20575740 TI - Succession of ground-dwelling beetle assemblages after fire in three habitat types in the Andean forest of NW Patagonia, Argentina. AB - Wildfires are one of the major disturbances in the dynamics of forests and shrublands. However, little is known about their effects on insect communities that contribute to faunal biodiversity and play key roles in the ecosystem's dynamics. An intense and widespread fire occurred in 1999 in the Nahuel Huapi National Park in the Andean forest in northern Patagonia, Argentina. This fire affected adjacent, but different, habitat types. After the fire, beetle abundance, species richness and assemblage composition were compared among three habitats that were structurally different before the fire. These habitats were: 1) evergreen forest dominated by Nothofagus dombeyi (Mirb.) Oerst. (Fagales: Nothofagaceae), 2) a mixed forest of the evergreen conifer Austrocedrus chilensis (D. Don) Pic. Serm. and Bizzarri (Pinales: Cupressaceae) and N. dombeyi and 3) a shrubland with a diverse community of shrub species. The relationship between beetle diversity and vegetation structure was investigated over three consecutive years. Ground beetles were collected by pitfall traps, and plant species richness, vegetation cover, and height were measured. Beetle communities varied more over years between habitats during the early regeneration after fire. There was a shift in beetle assemblage composition with time after the fire in all habitat types, probably due to similar colonization rates and microclimatic conditions. Therefore, beetle succession was more influenced by recolonization and survivorship, accompanied by climatic conditions and recovery rate of plant communities over time, than it was influenced by pre-fire habitat conditions. These results suggest that in NW Patagonia, wildfire can have a substantial, short-term impact on beetle abundance and species composition. The pre-fire conditions of each habitat type determined the structure of post-fire communities of plants but not beetle assemblages. Wildfires produce simplification and homogenization of habitat types, and this was reflected by beetle diversity. PMID- 20575741 TI - Niches and interspecific competitive relationships of the parasitoids, Microplitis prodeniae and Campoletis chlorldeae, of the Oriental leafworm moth, Spodoptera litura, in tobacco. AB - Both Microplitis prodeniae Rao and Chandry (Hymenoptera: Bracondidae) and Campoletis chlorideae Uchida (Hymenoptera: Ichnumonidae) are major parasitoids of Spodoptera litura (Fabricious) (Lepidoptera: Noctuidae) in tobacco, Nicotiana tabacum L. (Solanales: Solanaceae) at Nanxiong, Guangdong Province, South China. The niches and interspecific competition relationships of the two species were studied. The results show that the competition between the two species for spatial and food resources was very intense, and C. chlorideae was always dominant when the two species compete for spatial and food resources in different periods. Thus C. chlorideae may drive M. prodeniae away when they occupy the same spatial or food resource. The adaptability of C. chlorideae to the environment in the tobacco fields may be greater than that of M. prodeniae, so C. chlorideae can maintain a higher population compared to that of M. prodeniae. PMID- 20575742 TI - A review of the natural history and laboratory culture methods for the yellow dung fly, Scathophaga stercoraria. AB - The yellow dung fly Scathophaga stercoraria (L.) (Diptera: Scathophagidae) is a widespread and locally abundant fly associated with the dung of large mammals, especially farm animals. This species has recently become a standard test organism for evaluating toxic effects of veterinary pharmaceuticals in livestock dung. In this context, a review of its natural history and a general description of the field and laboratory rearing methods of this species are provided here to benefit the scientific community as well as government regulators and applicants of eco-toxicological studies. For guidance, means and ranges are included for all relevant standard life history traits stemming from previously published data on Swiss populations. PMID- 20575743 TI - Quantification and evidence for mechanically metered release of pygidial secretions in formic acid-producing carabid beetles. AB - This study is the first to measure the quantity of pygidial gland secretions released defensively by carabid beetles (Coleoptera: Carabidae) and to accurately measure the relative quantity of formic acid contained in their pygidial gland reservoirs and spray emissions. Individuals of three typical formic acid producing species were induced to repeatedly spray, ultimately exhausting their chemical compound reserves. Beetles were subjected to faux attacks using forceps and weighed before and after each ejection of chemicals. Platynus brunneomarginatus (Mannerheim) (Platynini), P. ovipennis (Mannerheim) (Platynini) and Calathus ruficollis Dejean (Sphodrini), sprayed average quantities with standard error of 0.313 +/- 0.172 mg, 0.337 +/- 0.230 mg, and 0.197 +/- 0.117 mg per spray event, respectively. The quantity an individual beetle released when induced to spray tended to decrease with each subsequent spray event. The quantity emitted in a single spray was correlated to the quantity held in the reservoirs at the time of spraying for beetles whose reserves are greater than the average amount emitted in a spray event. For beetles with a quantity less than the average amount sprayed in reserve there was no significant correlation. For beetles comparable in terms of size, physiological condition and gland reservoir fullness, the shape of the gland reservoirs and musculature determined that a similar effort at each spray event would mechanically meter out the release so that a greater amount was emitted when more was available in the reservoir. The average percentage of formic acid was established for these species as 34.2%, 73.5% and 34.1% for for P. brunneomarginatus, P. ovipennis and C. ruficollis, respectively. The average quantities of formic acid released by individuals of these species was less than two-thirds the amount shown to be lethal to ants in previously published experiments. However, the total quantity from multiple spray events from a single individual could aggregate to quantities at or above the lethal level, and lesser quantities are known to act as ant alarm pheromones. Using a model, one directed spray of the formic acid and hydrocarbon mix could spread to an area of 5-8 cm diameter and persisted for 9-22 seconds at a threshold level known to induce alarm behaviors in ants. These results show that carabid defensive secretions may act as a potent and relatively prolonged defense against ants or similar predators even at a sub-lethal dose. PMID- 20575744 TI - Dietary effects of four phytoecdysteroids on growth and development of the Indian meal moth, Plodia interpunctella. AB - Using pure phytoecdysteroids isolated from Ajuga iva (L.) Schreber (Lamiales: Lamiaceae) and Silene nutans L. (Caryophyllales: Caryophyllaceae), plants known for their high ecdysteroid content, a study was carried out on the effects of ingestion of four different phytoecdysteroids (20-hydroxyecdysone, polypodine B, ponasterone A and makisterone A) on the growth and development of the Indian meal moth, Plodia interpunctella Hubner (Lepidoptera: Pyralidae) larvae when added at a concentration of 200 ppm in their diet. The experiments clearly showed the susceptibility of P. interpunctella to phytoecdysteroid ingestion. The toxicity of phytoecdysteroids manifested itself by a decrease in larval weight, induction of cannibalism and an increase of mortality, together with disruption of development. The severity of the phytoecdysteroid effect on P. interpunctella depended on the structure of the molecule. The results demonstrate that the minimal structural differences existing between these four phytoecdysteroids significantly affected their toxicity toward P. interpunctella. Makisterone A was the most toxic of the four compounds towards P. interpunctella larvae. In conclusion, phytoecdysteroids ingestion evokes disruptive growth effects on P. interpunctella. This work supports a role for phytoecdysteroids in plant defence against phytophagous insects. PMID- 20575746 TI - Morphological description of the immatures of the ant, Monomorium floricola. AB - Some ant species of the genus Monomorium Mayr occur worldwide and are considered important urban pests. The larvae of only a few species of this genus have been described, and these descriptions are either superficial or incomplete. This study aimed to determine the number of larval instars and describe the immature stages of the ant Monomorium floricola Jerdon (Formicidae: Myrmicinae). Specimens were analyzed and measured using light and scanning electron microscopy. Three larval instars were found, and all larvae had pheidoloid bodies with ectatommoid mandibles, consistent with other Monomorium species described previously. Five types of body hairs were described, and their distribution was instar-specific. Body and mandible dimensions of the larvae also were constant for each instar. Like other Myrmicinae, the larvae did not create a cocoon. Some of differences among the hair types and sensilla were observed by comparing the samples with larvae of other species in the genus, and these differences may have taxonomic utility. PMID- 20575745 TI - Alkaline phosphatase from venom of the endoparasitoid wasp, Pteromalus puparum. AB - Using chromogenic substrates 5-bromo-4-chloro-3'-indolyl phosphate and nitro blue tetrazolium, alkaline phosphatase (ALPase) was histochemically detected in the venom apparatus of an endoparasitoid wasp, Pteromalus puparum L. (Hymenoptera: Pteromalidae). Ultrastructural observations demonstrated its presence in the secretory vesicles and nuclei of the venom gland secretory cells. Using p nitrophenyl phosphate as substrate to measure enzyme activity, the venom ALPase was found to be temperature dependent with bivalent cation effects. The full length cDNA sequence of ALPase was amplified from the cDNA library of the venom apparatus of P. puparum, providing the first molecular characterization of ALPase in the venom of a parasitoid wasp. The cDNA consisted of 2645 bp with a 1623 bp open reading frame coding for 541 deduced amino acids with a predicted molecular mass of 59.83 kDa and pI of 6.98. Using multiple sequence alignment, the deduced amino acid sequence shared high identity to its counterparts from other insects. A signal peptide and a long conserved ALPase gene family signature sequence were observed. The amino acid sequence of this venom protein was characterized with different potential glycosylation, myristoylation, phosphorylation sites and metal ligand sites. The transcript of the ALPase gene was detected by RT-PCR in the venom apparatus with development related expression after adult wasp emergence, suggesting a possible correlation with the oviposition process. PMID- 20575748 TI - Widespread use of point-of-care testing is irreconcilable with the present-day quest for safety. PMID- 20575747 TI - Evaluation of a multiplex assay for adipokine concentrations in obese children. AB - BACKGROUND: Multiplexed bead immunoassays allow simultaneous measurement of adipokines and other hormones in small serum samples, although a validation of this technique with classical methods has not been fully established. The purpose of this pilot study was to compare the characteristics of a multiplexed bead immunoassay obesity panel for insulin and various adipokines with classical methods. METHODS: A multiplexed bead immunoassay was performed using serum from 20 obese children at baseline and after reducing their body mass index, and in 25 controls. Insulin, adiponectin, leptin, resistin, tumor necrosis factor-alpha and interleukin-6 measured by multiplexed bead immunoassay were compared with results obtained from commercial immunoassays. Correlation, sensitivity, recovery, linearity, performance and imprecision were established for each analyte. RESULTS: The correlation between methods was acceptable for adiponectin, leptin, and insulin with coefficients of 0.75-0.89 (p<0.001). Correlation was weak for resistin (0.54, p<0.001) and poor (r<0.30) for tumor necrosis factor-alpha and interleukin-6. However, Bland-Altman analysis indicated agreement for insulin methods (bias=-0.07), avoiding direct comparison with other analytes (bias>1.25). The imprecision was similar for both methods (<13%). Multiplexed immunoassay had a broader dynamic range than classical methods (4.94 times). The magnitude of the changes in serum concentrations after weight loss was comparable with both methods for adiponectin, leptin, insulin and resistin, resulting in similar statistical significance. Changes in tumor necrosis factor-alpha and interleukin 6 were detected by classical immunoassays only (p<0.05). CONCLUSIONS: This study demonstrates that multiplexed bead immunoassay is more cost effective for measurement of adipokines present in relatively large amounts, diminishing inter assay variations and reducing the sample volume. PMID- 20575749 TI - VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of hepatocellular carcinoma. AB - BACKGROUND: PIVKAII (protein induced by vitamin K absence), used for screening for hepatocellular carcinoma (HCC), is influenced by vitamin K epoxide reductase complex subunit 1 (VKORC1). VKORC1 haplotype frequency is significantly different in ethnic groups. We evaluated whether VKORC1 haplotypes could influence the performance characteristics of PIVKAII in screening for HCC. METHODS: A total 228 HCC patients and 258 patients with hepatitis B were recruited. Tumor size was measured in 76 patients with HCC. Serum PIVKAII concentrations and VKORC1 haplotype were determined in the cohort. Youden's index and ROC curves were used to compare the performance characteristics of PIVKAII in screening for HCC. RESULTS: In the HCC group and in patients with hepatitis B, serum PIVKAII concentrations were higher in VKORC1 rs2395612 TT carriers than in CC/CT carriers (50.34+/-72.18 vs. 11.98+/-27.45, p<0.05 in HCC group and 1.92+/-0.52 vs. 1.48+/ 0.36, p<0.01). The estimated optimal cut-off value of PIVKAII for screening HCC was 2.0 and 3.0 ng/mL in CC/CT carriers and TT carriers, respectively. Furthermore, VKORC1 haplotypes also influenced the association of serum PIVKAII concentrations with HCC tumor size in patients with HCC. CONCLUSIONS: VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of HCC. Thus, measurement could be complementary for PIVKAII in HCC screening. PMID- 20575750 TI - Exercise has a role in the rehabilitation process. PMID- 20575751 TI - Physical activity in young children with cerebral palsy. AB - PURPOSE: The aim of this study was to describe the physical activity levels of 5- and 7-year-old children with cerebral palsy (CP, n = 97), to compare their physical activity levels with those of typically developing peers (TD, n = 57) and the Dutch recommendation for physical activity, and to investigate the associated factors. METHOD: The level of physical activity (hours spent on sports and physical activity per week) and contextual factors were assessed with standardised questionnaires. RESULTS: Mean duration of self-reported physical activity for children with CP was 3.4 (+/- 1.9) h/week, which was significantly less than the 5.8 (+/- 2.3) h/week for TD-peers. Ninety-three percent of the children with CP were insufficiently physically active according to the Dutch recommendation for physical activity. Multiple regression analyses showed that younger age and lower educational level of the mother were significantly associated with lower levels of physical activity for children with CP, while severity of CP was not associated with physical activity levels. Twenty-two percent of the parents reported that more facilities in sport and games are required for children with CP. CONCLUSION: Physical activity is low in young children with CP and needs to be promoted at an early stage. PMID- 20575752 TI - Implicit and explicit learning: applications from basic research to sports for individuals with impaired movement dynamics. AB - PURPOSE: Motor skills can be learned in an explicit or an implicit manner. Explicit learning places high demands on working memory capacity, but engagement of working memory is largely circumvented when skills are learned implicitly. We propose that individuals with impaired movement dynamics may benefit from implicit learning methods when acquiring sports-related motor skills. METHOD: We discuss converging evidence that individuals with cerebral palsy and children born prematurely have compromised working memory capacity. This may in part explain the difficulties they encounter when learning motor and other skills. We also review tentative evidence that older people, whose movement dynamics deteriorate, can implicitly learn sports-related motor skills and that this results in more durable performance gains than explicit learning. RESULTS: Individuals with altered movement dynamics and compromised working memory can benefit from implicit motor learning. CONCLUSION: We conclude with an appeal for more extensive evaluation of the merits of implicit motor learning in individuals with impaired movement dynamics. PMID- 20575753 TI - A 'visual-centred' mapping approach for improving access to Web 2.0 for people with visual impairments. AB - On simple Web pages, the text to speech translation provided by a screen reader works relatively well. This is not the case for more sophisticated 'Web 2.0' pages, in which many interactive visual features, such as tickers, tabs, auto suggest lists, calendars and slideshows currently remain inaccessible. Determining how to present these in audio is challenging in general, but may be particularly so for certain groups, such as people with congenital or early-onset blindness, as they are not necessarily familiar with the visual interaction metaphors that are involved. This article describes an evaluation of an audio Web browser designed using a novel approach, whereby visual content is translated to audio using algorithms derived from observing how sighted users interact with it. Both quantitative and qualitative measures showed that all participants, irrespective of the onset of their visual impairment, preferred the visual interaction-based audio mappings. Participants liked the fact that the mappings made the dynamic content truly accessible, rather than merely available to those who could find it, as is presently the case. The results indicate that this 'visual-centred' mapping approach may prove to be a suitable technique for translating complex visual content to audio, even for users with early-onset visual disabilities. PMID- 20575758 TI - Enzyme stereospecificity as a powerful tool in searching for new enzymes. AB - Chirality is a ubiquitous feature present in all biological systems that plays a very important role in many processes. Drug metabolism is one of these and is the subject of this review. Chiral drugs can be metabolized without changes in their chiral characteristics, but also their biotransformation may give rise to a new chiral center. On the other hand, prochiral drugs are always metabolized to chiral metabolites. The ratio of formed enantiomers/diastereoisomers is the constant known as enzyme stereospecificity, and this is as important a characteristic for each enzyme-substrate pair as is the Michaelis constant. Drugs are often substrates for multiple biotransformation enzymes, and all enzymes involved may metabolize a chiral or prochiral drug with different stereospecificity so that variant enantiomer ratios are achieved. Enzyme stereospecificity of whole cell fraction is the sum of the stereospecificities of all enzymes participating in metabolism of a substrate. Differing stereospecificities in the metabolism of a drug between whole cell fraction and enzymes point to the contribution of other enzymes. Using several drugs as examples, this review shows that enzyme stereospecificity can serve as a powerful tool in searching for new biotransformation enzymes. Although it is not often used in this way, it is clear that this is possible. There are today drugs with well-known chiral metabolism, but, inasmuch as many xenobiotics are poorly characterized in terms of chiral metabolism, enzyme stereospecificity could be widely utilized in researching such substances. PMID- 20575759 TI - Direct analysis of glucuronides with liquid chromatography-mass spectrometric techniques and methods. AB - Glucuronidation is one of the main phase II metabolic reactions in humans and animals. A variety of analytical techniques and methods have been used for the detection and quantification of glucuronides of both endogenous and xenobiotic compounds from different biological samples of humans and animals. Drug metabolism has been extensively studied with both in vitro and in vivo experiments under various conditions. The purpose of this review is to explore in detail the benefits and drawbacks of different liquid chromatography-mass spectrometric (LC/MS) methods and techniques in detection and identification of all forms of glucuronide conjugates from in vitro, biological, and environmental samples. The entire analytical procedure is covered, from sample treatment, separation, and ionization to qualitative and quantitative analyses. The aim of this review is not to cover every published paper where glucuronides are identified and/or quantified, but rather to focus on special cases where a new analytical approach or technical development has led to a better, more specific, or more comprehensive detection, identification, or quantitation of glucuronide conjugates. PMID- 20575760 TI - Biphasic regulation of H2O2 on angiogenesis implicated NADPH oxidase. AB - ROS (reactive oxygen species) take an important signalling role in angiogenesis. Although there are several ways to produce ROS in cells, multicomponent non phagocytic NADPH oxidase is an important source of ROS that contribute to angiogenesis. In the present work, we examined the effects of H2O2 on angiogenesis including proliferation and migration in HUVECs (human umbilical vein endothelial cells), new vessel formation in chicken embryo CAM (chorioallantoic membrane) and endothelial cell apoptosis, which is closely related to anti-angiogenesis. Our results showed that H2O2 dose-dependently increased the generation of O2- (superoxide anion) in HUVECs, which was suppressed by DPI (diphenylene iodonium) and APO (apocynin), two inhibitors of NADPH oxidase. H2O2 at low concentrations (10 microM) stimulated cell proliferation and migration, but at higher concentrations, inhibited both. Similarly, H2O2 at 4 nmol/cm2 strongly induced new vessel formation in CAM, while it suppressed at high concentrations (higher than 4 nmol/cm2). Also, H2O2 (200 approximately 500 microM) could stimulate apoptosis in HUVECs. All the effects of H2O2 on angiogenesis could be suppressed by NADPH oxidase inhibitors, which suggests that NADPH oxidase acts downstream of H2O2 to produce O2- and then to regulate angiogenesis. In summary, our results suggest that H2O2 as well as O2- mediated by NADPH oxidase have biphasic effects on angiogenesis in vitro and in vivo. PMID- 20575761 TI - Sterol-regulatory-element-binding protein 1c mediates the effect of insulin on the expression of Cidea in mouse hepatocytes. AB - Members of the Cide [cell death-inducing DFFA (DNA fragmentation factor-alpha) like effector] gene family have been reported to be associated with lipid metabolism. In the present study, we show that Cidea mRNA levels are markedly reduced by fasting and are restored upon refeeding in mouse livers. To elucidate the molecular mechanism, the promoter region of the mouse Cidea gene was analysed and a putative SRE (sterol-regulatory element) was identified. Studies using luciferase reporter constructs together with electrophoretic mobility-shift assays and chromatin immunoprecipitation confirmed the binding of SREBP-1c (SRE binding protein 1c) to the putative SRE. Furthermore, adenovirus-mediated overexpression of SREBP-1c led to a dramatic increase in Cidea mRNA. In contrast with the induction of Cidea expression by insulin and TO901317 in wild-type mouse hepatocytes, the stimulatory effects were lost in hepatocytes prepared from SREBP 1c-null mice. Adenovirus-mediated overexpression of Cidea in hepatocytes promoted lipid accumulation and triacylglycerol (triglyceride) storage; however, knockdown of Cidea compromised the ability of SREBP-1c to stimulate lipid accumulation. Taken together, these results suggest that SREBP-1c directly mediates the effect of insulin on Cidea in hepatocytes and that Cidea, at least in part, mediates SREBP-1c-dependent lipid accumulation. PMID- 20575762 TI - Intermolecular phosphotransfer is crucial for efficient catalytic activity of nucleoside diphosphate kinase. AB - NDK (nucleoside diphosphate kinase) is primarily involved in maintaining cellular nucleotide pools in both prokaryotes and eukaryotes. We cloned ndk from Salmonella typhimurium and expressed it in Escherichia coli as a histidine-tagged protein. The Ni-NTA (Ni(2+)-nitrilotriacetate)-purified protein (sNDK) was found to be tetrameric with a monomeric unit molecular mass of approximately 18 kDa. The sNDK exhibited bivalent-cation-dependent autophosphorylation at a wide range of pH values and the phosphorylation withstands acid or alkali treatment. Surprisingly, nucleoside diphosphates did not behave as 'true inhibitors' of autophosphorylation activity. The sNDK displayed phosphotransfer activity from nucleoside triphosphates to nucleoside diphosphates; however, it was Mg(2+)/Mn(2+)-dependent. Mutational analysis established His(117) as the predominantly phosphorylating residue in sNDK. Although it is a histidine kinase, we found that substitution of Ser(119) with alanine/glutamate significantly affected the autophosphorylation, as well as the NTP-synthesizing ability of sNDK. Interestingly, the mixture of inactive (H117A) and partially active (S119A) proteins was found to be catalytically more efficient than the presence of corresponding amounts of active population, advocating transfer of phosphate from phospho-His(117) to Ser(119). Consistent with this observation, the Ni-NTA purified H117A protein, obtained following co-expression of both of the mutant constructs [His-tagged H117A and GST (glutathione transferase)-tagged S119A] in E. coli, exhibited autophosphorylation, thereby alluding to intermolecular phosphotransfer between His(117) and Ser(119). Although this housekeeping enzyme has long been discovered and characterized from different sources, the results of the present study portray how Ser(119) in sNDK is phosphorylated. Furthermore, our findings illustrate for the first time that the intermolecular phosphotransfer is mandatory for the efficient NTP synthesis in any NDK. PMID- 20575764 TI - Mutagenicity, developmental toxicity and carcinogenicity of cannabis. AB - Data on the mutagenicity, developmental toxicity and carcinogenicity of cannabis are reviewed in this article. The available evidence on the possible mutagenic effects of cannabinoids is still inconclusive. There is no consensus on the induction of point mutations, while some experimental results suggest that cannabinoids may cause chromosomal damage. Concerning the developmental effects of cannabis, an increased embryolethality and somatic growth retardation have been observed in animals, as well as changes in motor behaviour, after perinatal exposure to cannabinoids. An elevated risk for infertility has been suggested for women smoking marijuana. On the other hand, intrauterine exposure to cannabinoids may be followed by changes of behaviour later in childhood. Finally, the experimental work concerning the possible carcinogenic action of cannabinoids has shown that cannabis acts as a tumour promotor in animals. Epidemiological studies have incriminated cannabis smoking for the development of head and neck carcinomas and for carcinomas of the respiratory tract in humans, but several confounding factors have rendered this evidence inconclusive. At least part of the great popularity of cannabis smoking is due to the widespread belief that it is harmless. However, the studies presented in this review show that, despite their low acute toxicity profile, cannabinoids represent several risks in terms of chronic toxicity. PMID- 20575763 TI - Prevalence and prognostic implications of active cytomegalovirus infection in patients with acute heart failure. AB - AHF (acute heart failure) causes significant morbidity and mortality. Recent studies have postulated that the expression of inflammatory mediators, such as cytokines and chemokines, plays an important role in the development and progression of heart failure. A pro-inflammatory state has been postulated as a key factor in triggering CMV (cytomegalovirus) reactivation. Therefore we sought to determine the prevalence of active CMV infection in immunocompetent patients admitted for AHF and to quantify the association with the risk of the combined end point of death or AHF readmission. A total of 132 consecutive patients admitted for AHF were enrolled in the present study. Plasma CMV DNAaemia was assessed by qRT-PCR (quantitative real-time PCR), and cytokine measurements in plasma were performed by ELISA. Clinical data were evaluated by personnel blinded to CMV results. The independent association between active CMV infection and the end point was determined by Cox regression analysis. During a median follow-up of 120 [IQR (interquartile range), 60-240] days, 23 (17.4%) deaths, 34 (24.2%) readmissions for AHF and 45 (34.1%) deaths/readmissions for AHF were identified. Plasma CMV DNAaemia occurred in 11 (8.3%) patients, albeit at a low level (<100 copies/ml). The cumulative rate of the composite end point was higher in patients with CMV DNAaemia (81.8 compared with 29.8%; P<0.001). After adjusting for established risk factors, the occurrence of CMV DNAaemia was strongly associated with the clinical end point [hazard ratio = 4.39 (95% confidence interval, 2.02 9.52); P<0.001]. In conclusion, active CMV infection occurs, although uncommonly, in patients with AHF, and may be a marker of disease severity. PMID- 20575765 TI - Pancreatitis-associated proteins: experimental and clinical studies. AB - Various novel biochemical markers indicate pancreatic cellular injury more accurately than serum amylase or lipase. One of these is a non-enzymatic secretory protein called pancreatitis-associated protein (PAP).The main function of PAP is unclear at present but it may be an acute phase protein in the defence reactions of pancreatic cells. The protein was characterized in 1984 as a serum marker of pancreatitis. The serum PAP is expressed 6 hours after the induction of pancreatitis, and it increases to maximal levels within 2-4 days: PAP is not sufficiently sensitive for the diagnosis of acute pancreatitis in the emergency room. The sensitivity and specificity of PAP in the differentiation of severe from mild pancreatitis is between 60-70%. This is not superior to serum CRP assays or CT scans. PAP increases in pancreatic cellular injury without pancreatitis (subclinical cell damage, graft rejection) where PAP may have a diagnostic role. PMID- 20575766 TI - Alcohol, smoking and lung disease. AB - Alcohol and smoking are two well-known health hazards. Alcohol and tobacco consumption are strongly correlated and heavy drinkers have more trouble quitting smoking than do light drinkers. Death from tobacco-related causes was more common than alcohol-related death in a follow-up study on patients admitted to an addiction programme for treatment of alcoholism and non-nicotine drug dependence. In British male doctors in the middle and elderly age group, a protective effect of light and moderate alcohol consumption (1-3 British units of alcohol per day) compared with abstinence has been shown in one large survey. This protective effect was shown in overall mortality as well as in mortality from respiratory disease. Higher alcohol intakes were associated with an increase in mortality. This characteristic U-formed, or J-formed, dose-response curve has been found in most studies with an apparent beneficial effect of modest alcohol intake and a harmful effect of high intakes. The anti-inflammatory effect of alcohol has been considered to be responsible for its limited protective effect on smoking-related lung function decline. Recently, a hitherto unconfirmed report suggests that the beneficial effect of alcohol on lung function in men is restricted to subjects with Lewis-negative blood group (10% of the Caucasian population). On the other hand, the protective effect in those individuals is large enough to be clinically relevant. Prospective investigations including both men and women are needed to elucidate which individuals have a protective effect of light and moderate alcohol intake. The major deleterious effect of smoking, including passive smoking, must be kept in mind-drinking alcohol surrounded by cigarette smoke might not be beneficial for respiratory health. PMID- 20575767 TI - Alcohol problems in a general hospital. AB - Alcohol is a ubiquitous drug which is responsible for a substantial amount of ill health and approximately 20% of patients in a general hospital will have alcohol related problems, although only 4% will be admitted with alcohol-caused conditions. Eight per cent of patients, however, can be expected to have sufficient neuroadaptation to be at risk of withdrawal. This level of prevalence of alcoholism in general hospital patients requires that hospitals must become expert at providing good quality care for alcohol-related problems in all areas including obstetrics, but particularly in the management of intoxication, withdrawal and the various alcohol-related diseases. This paper provides some suggested benchmarks for acceptable standards of care for alcohol problems in the acute hospital. PMID- 20575768 TI - Concurrent chronic administration of a CCK(B) antagonist can decrease tolerance to the ataxic effects of ethanol. AB - The effects of chronic administration of a CCK(B) antagonist, CAM1028, were examined on the development of tolerance to ethanol and the appearance of withdrawal signs. Ethanol was given chronically by liquid diet, and none of the dose schedules of CAM1028 affected the amount of ethanol taken in during the chronic treatment. Brain ethanol concentrations were not altered by the administration of CAM1028.The ataxic effects of ethanol were tested on a rotorod, 3 hours after cessation of the ethanol administration, and the last injections of CAM1028 were given 8 hours before withdrawal from the ethanol treatment. When administered at 0.03, 0.1 or 0.3 mg/kg, CAM1028 decreased the extent of tolerance development. Higher doses, 1 and 3 mg/kg, did not alter the tolerance development. Chronic administration of CAM1028 had a small effect in protecting against the effects of ethanol withdrawal that, in contrast to the effects on the tolerance, was seen only at the highest dose, 10 mg/kg, of CAM1028. PMID- 20575769 TI - Ethanol induces taurine release in the amygdala: an in vivo microdialysis study. AB - The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with total brain ethanol. Each acute intraperitoneal injection of ethanol, 0.5, 1.0, 2.0 and 3.0 g/kg body weight, induced an immediate increase in microdialysate taurine; both 0.5 and 1.0 g/kg ethanol evoked an increase during the first 20 minutes following injection which returned to baseline value by 40 minutes, despite the fact that ethanol was detectable in the brain until 60 or 120 minutes, respectively. After either 2.0 or 3.0 g/kg ethanol there was an increase in taurine of gradual intensity which gradually declined to reach baseline values by 100 minutes. In contrast, the ethanol concentration for 2.0 g/kg remained elevated at the end of the 120 minutes; approximately 25 mg ethanol/mg protein. The stimulated release of taurine within the amygdala could participate in the regulation of ethanoli nduced changes in osmolarity, since taurine is postulated to act as an osmoregulator in the brain. Taurine could also mediate or interact with ethanol induced central nervous system effects, as it exerts a modulatory action on cell excitability and neurotransmitter processes. PMID- 20575770 TI - Oxidation of acetaldehyde by isolated aortic rings of UChA and UChB rats. AB - The rate of acetaldehyde metabolism was measured in aortic rings from rat strains genetically bred for high (UChB) and low (UChA) voluntary ethanol consumption. The results show that in aortic rings from naive UChB rats, acetaldehyde oxidation rates were significantly greater than the rates observed in aortic rings from naive UChA rats. These strain differences are explained by different activity of vascular low-Km aldehyde dehydrogenase (ALDH). Chronic feeding of ethanol to UChA rats did not alter their aortic ALDH activity. The results of the present study provides additional evidence that the activity variation for the low-Km ALDH between both rat strains exists in various organs and tissues. PMID- 20575772 TI - Effect of diazepam on growth hormone secretion in abstinent alcoholic men. AB - The present study was performed in order to establish, with a simple and safe neuroendocrinological test, whether alcoholism is associated with alterations in sensitivity to benzodiazepines. For this purpose, we tested the stimulatory effects of diazepam on GH secretion. An intravenous bolus of 10 mg diazepam was injected in 51 (33-51-year-old) alcoholic men after at least 5 weeks of abstinence and in 20 age- and weight-matched normal controls. On a different occasion, a control test with placebo (physiological saline) was performed in the same subjects. Diazepam but not placebo administration induced a striking increase of GH secretion in the normal controls. In contrast, neither diazepam nor placebo treatment significantly changed the basal serum GH levels in alcoholic men. These data show that alcoholism is associated with disrupted benzodiazepine activity on the hypothalamic-pituitary control of GH secretion. The simplicity of the diazepam GH-releasing test makes the drug suitable for clinical research in alcoholism. PMID- 20575771 TI - The DRD2A1allele: a behavioural genetic risk factor in hepatitis C infection of persistent drug abusers. AB - Hepatitis C is highly prevalent among intravenous drug abusers, but to date research has not widely explicated behavioural risk factors regarding acquisition of infection. The A1allele of the D2 dopamine receptor (DRD2) gene is a hypothesized risk factor in the development of severe drug dependence and alcoholism. The present study compares the frequency of the A1 allele of the DRD2 gene among 37 patients presenting to a hepatitis clinic for treatment of hepatitis C, 23 hepatitis C-negative drug-abusing patients maintained on methadone and 33 non-drug-abusing controls. The results indicated that hepatitis C-positive patients were significantly more likely to display the A1 allele than hepatitis C-negative patients, who were in turn more likely to have the A1 allele than controls. Furthermore, the hepatitis C subjects manifested more persistent drug-seeking behaviour than the other drug-abusing group. The implications of this finding in terms of drug-related reward are discussed. Future research should attempt to evaluate host risk factors, in order to enable more precisely targeted attempts at harm minimization. PMID- 20575773 TI - The urinary MHPG/creatinine ratio and its relationship to platelet monoamine oxidase activity in abstinent alcoholics. AB - This study was designed to assess the baseline noradrenergic turnover of subgroups of postwithdrawal abstinent alcoholics and healthy controls. The method chosen was an overnight fasting urine sample of the breakdown product of norepinephrine, MHPG, related to urinary creatinine. A comparison was made with platelet monoamine oxidase activity and also within subgroups of the study population. This study found no difference between alcoholics and controls, nor between subgroups of postwithdrawal alcoholics in their level of urinary MHPG corrected for creatinine, and no significant correlation with major subject characteristics or with platelet monoamine oxidase. There was a trend, however, towards a significant correlation with duration of abstinence from alcohol, and there was a correlation with a history of fighting when drinking alcohol, but not with sociopathic traits overall. Within the type 2 alcoholics there was a significant correlation with a history of fighting when drinking and a negative correlation with behavioral tolerance to alcohol. It is possible that only the subset of type 2 alcoholics with certain antisocial characteristics have noradrenergic abnormalities. Although no statistical difference was found between the different groups under study, the information is helpful in increasing understanding of the noradrenergic system in abstinent alcoholics. PMID- 20575774 TI - A comparison of five commercial immunoassays for the detection of flunitrazepam and other benzodiazepines in urine. AB - Five commercially available immunoassay test kits (SYVA EMIT(R) d.a.u(TM), SYVA EMIT(R) II assay, Abbott FPIA, Cozart Auto-Lyte(R) and Roche Abuscreen(R) Online(TM), all used for the benzodiazepine group of drugs) were evaluated for their ability to detect flunitrazepam, its major urinary metabolite, 7 aminoflunitrazepam, and several other benzodiazepines at serial dilutions (final concentration 25-1000 ng/ml) in drug-free urine and in urines following oral administration of flunitrazepam (1-3 mg). For comparison, gas chromatography/mass spectrometry was used to measure urinary levels of 7-aminoflunitrazepam. Levels of drug detected in the study were compared with the cross-reactivities presented by the manufacturers for each individual kit. One to three mg doses of flunitrazepam were taken by volunteers and levels excreted in urine analysed over several hours. A positive response was obtained in several samples from volunteers who had taken 2 mg or 3 mg doses, but not a 1 mg dose. Thirty-five clinical samples from the individuals suspected of benzodiazepine abuse were also examined. The results were not consistent among the kits evaluated.We conclude that the test kits evaluated in this study do not detect flunitrazepam reliably, due primarily to their poor sensitivities. PMID- 20575775 TI - The corticosteroid synthesis inhibitor metyrapone markedly enhances the behavioural effects of d-amphetamine. AB - The clinically utilized corticosteroid synthesis inhibitor metyrapone attenuates the behavioural effects of cocaine in the rat. Given the potential therapeutic implications of this interaction, we felt it important to determine if metyrapone's action would generalize to another widely abused psychostimulant, namely d-amphetamine. However, rather than producing attenuation, metyrapone preadministration (3 x 100 mg/kg) markedly enhanced both the locomotor activating and stereotypy-inducing actions of d-amphetamine (dose equivalent to 2.5 mg/kg free base). The fact that the corticosteroid synthesis inhibitor trilostane did not affect the behavioural action of d-amphetamine suggests that inhibition of corticoid synthesis does not underlie the action of metyrapone. Instead, it is argued that inhibition of debrisoquine hydroxylase (cytochrome p450 2D1), an enzyme involved in the metabolism of d-amphetamine, represents the critical mechanism of action. PMID- 20575777 TI - Impact factors: believe them or not. PMID- 20575778 TI - Biomedical benefits of cannabinoids? AB - Cannabinoids appear to be of therapeutic value as antiemetics, antispasmodics, analgesics and appetite stimulants and may have potential uses in epilepsy, glaucoma and asthma. Scientific evidence for any of these indications, except for antiemetic effects, is extremely sparse and claims for clinical utility are largely based on anecdotal reports. Furthermore, the mechanisms of action of any of the therapeutic effects are unknown. This paper reviews the clinical trials which have been carried out with cannabinoids including Delta9 tetrahydrocannabinol (THC) and synthetic cannabinoids such as nabilone and levonantradol, and discusses the advantages and adverse effects of cannabinoids in clinical use. The place of cannabinoids in modern medicine remains to be properly evaluated, but present evidence suggests that they could be valuable, particularly as adjuvants, for symptom control in a range of conditions for which standard drugs are not fully satisfactory. PMID- 20575779 TI - Cocaethylene: effects on brain systems and behavior. AB - Cocaethylene is a psychoactive metabolite formed during the combined consumption of cocaine and ethanol. In this brief review, we discuss several well characterized effects of this metabolite with an emphasis on the neurobiological and behavioral correlates of polydrug addiction. Included herein are the descriptions of some of the changes in trans-synaptic transmission and their relationship to pathological behaviors associated with a chronic, drug-dependent state that may be altered by the spatial or temporal dynamics of cocaethylene. PMID- 20575780 TI - Glutamate-dopamine interactions mediate the effects of psychostimulant drugs. AB - The striatum, a major central nervous system structure modulating movement, is enriched with glutamatergic and dopaminergic innervation. By altering activities of both glutamatergic and dopaminergic transmissions the psychostimulants, amphetamine and cocaine, induce behavioral changes in experimental animals. Activation of the two systems is also essential in the mediation of drug stimulated gene expression in striatal neurons, which is considered to be an important component of the neuroplasticity underlying long-term profiles of stimulant use. Interactions between the two systems occur at multiple levels that determine the final outcome of drug stimulation. Emerging studies on the detailed transsynaptic and intracellular mechanisms of glutamatedopamine interactions in response to stimulant exposure are providing cellular and molecular insight into the pathophysiology of stimulant abuse. PMID- 20575781 TI - Carbohydrate-deficient transferrin in the assessment of harmful alcohol consumption: diagnostic performance and clinical significance. AB - The last decade saw the emergence of carbohydrate-deficient transferrin (CDT) as the most promising marker for the diagnosis of alcohol abuse. Daily alcohol consumption of four beers, four glasses of wine or three standard drinks causes increased concentrations of CDT in serum. CDT is serum transferrin with a reduced content of oligosaccharides due to the detrimental effects of alcohol metabolism on the glycosylation pathway of hepatocytes and/or the increased activity of circulating glycosidases in serum. Most current CDT procedures entail separation of normal transferrin from CDT in a charged matrix-like isoelectric focusing and ion exchange chromatography, followed by detection/quantitation of CDT by a myriad of immunoassays: immunoblotting, radioimmunoassay, enzyme immunoassay and nephelometry. New CDT procedures present the advantages of improved performance, inexpensive automation and CDT results expressed as a percentage of total serum transferrin. CDT's major asset is its high specificity in well-defined populations i.e. individuals ingesting 60 g alcohol daily for at least a week.The sensitivity rates, which vary between 22% and 81%, depend on the amount of alcohol ingested, time of sample collection after the cessation of drinking, age, gender and the cut-off point chosen for analysis of tests' results. Regarding clinical applications, best outcome is achieved when the test is used to confirm a suspicion of alcohol abuse and when monitoring abstinence and relapses.The low prevalence of alcohol abuse in the general population challenges its use as a screening test.With the advent of inexpensive automation and the constant emergence of innovative, improved tests, we are seeing the rise of a new era in alcohol abuse diagnosis as affordability and education allows widespread use of CDT in a variety of settings. PMID- 20575782 TI - Chronic effects of ethanol on muscarinic acetylcholine receptors are modulated by protein kinase C. AB - We have previously demonstrated that long-term ethanol treatment increased the number and function of muscarinic acetylcholine receptors (mAChRs) in human neuroblastoma cells, but the molecular mechanisms involved in these changes are unknown. In the present study, the effect of protein kinase C (PKC) on these events was investigated in human neuroblastoma SH-SY5Y cells. Following exposure to 100 mM ethanol for 2 days, both [3H]N-methylscopolamine binding and carbachol stimulated I(1,4,5)P3formation were increased. When cells were cultured in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent activator of PKC, the effects of ethanol on mAChR number were totally inhibited but ethanol still potentiated carbacholstimulated I(1,4,5)P3 formation in TPA treated cells. TPA dose-dependently inhibited carbochol-stimulated I(1,4,5)P3 formation and this effect appeared to be independent of PKC phosphorylating activity. On the other hand, PKC inhibitors mimicked ethanol effects on mAChR number and function. Selective inhibition of classical PKC isozymes with 1 MUMU Go 6976 for 2 days caused an increase in mAChR number and function, suggesting a role for these isozymes in ethanol-induced upregulation of mAChRs. These data indicate that longterm ethanol treatment may upregulate the number of mAChRs by counteracting PKC-mediated phosphorylation. The effects of ethanol on receptor-coupled phosphoinositide hydrolysis appear to be independent of PKC activity. PMID- 20575783 TI - Chronic alcohol administration in the rat pup: effects upon later consumption of alcohol and other palatable solutions. AB - Previous studies indicate that in rats, chronic alcohol exposure during the first weeks of life markedly affect subsequent ethanol consumption patterns. The present study examined the impact of different alcohol doses (0.5-3.0 g/kg), administered between postnatal days 6-12, upon subsequent infantile consumption of an ethanol solution as well as upon intake of various non-ethanol solutions (water, sucrose, quinine or sucrose mixed with quinine). Alcohol administration did not strongly affect consumption scores of water, sucrose or quinine. In contrast, 15-day-old pups pretreated with 2.0 and 3.0 g/kg alcohol doses showed significant increases in terms of alcohol consumption when compared to saline controls. Furthermore, a positive significant correlation was observed between alcohol intake patterns and alcohol dose administered during early ontogeny. Intake of sucrose mixed with quinine was also significantly and positively correlated with pretreatment ethanol dosage. Interestingly, this taste configuration has been shown to mimic psychophysical properties of ethanol in the rat. The results appear not to be explained by teratological effects of the drug upon sensory processing of distinctive tastants. It appears that chronic alcohol exposure during early ontogeny provides specific sensory-related alcohol information that later modulates alcohol intake patterns. PMID- 20575784 TI - The quantitative determination of R- and S-salsolinol in the striatum and adrenal gland of rats selectively bred for disparate alcohol drinking. AB - To explore the hypothesis that endogenous 1-methyl-6,7-dihydroxy-1,2,3,4 tetrahydroisoquinoline (salsolinol) might be involved in the etiology of alcoholism, its concentration was determined in the striatum and adrenal gland of rats bred selectively for disparate alcohol drinking. The alcohol-naive alcohol preferring (P) and the high-alcohol-drinking (HAD) lines of rats demonstrated significantly lower striatal and adrenal salsolinol content when compared with the alcohol-non-preferring (NP) and the low-alcohol-drinking (LAD) lines. In the P-line of rats, 4 weeks of free-choice alcohol drinking had no significant effect on striatal salsolinol levels, although adrenal levels of salsolinol were significantly higher. The salsolinol assayed in the striatum of all lines of rats occurred as a racemic mixture of enantiomers that was unchanged following 4 weeks of alcohol exposure. Unlike striatal tissue, the adrenals of alcohol naive P-rats contained significantly more S- than R-salsolinol (ratio S/R = 83/17) and alcohol consumption resulted in the formation of a nearly racemic mixture of enantiomers. These results suggest a role for genetic factors in the formation of endogenous salsolinol and its potential regulation by short-term alcohol intake. PMID- 20575785 TI - Effect of nicotinamide administration on ethanol consumption and on liver and brain acetaldehyde oxidation rate, by UChB rats. AB - The activities of liver and brain aldehyde dehydrogenase, an NAD(+) dependent enzyme, which controls acetaldehyde oxidation have been reported to play a role in voluntary ethanol consumption. It has been reported that nicotinamide administration to rats increases NAD(+) levels, that may increase acetaldehyde oxidation rates if basal NAD(+) levels are not saturating for the enzyme. In the present paper the effect of nicotinamide administration on voluntary ethanol consumption by genetically high ethanol consumer UChB rats and brain and liver mitochondrial acetaldehyde oxidation were studied. Administration of nicotinamide 250 or 500 mg/kg i.p. to UChB rats, produced a significant reduction in their voluntary ethanol consumption and increased brain acetaldehyde oxidation in brain but not liver homogenates.These results suggest that basal NAD(+) levels are not saturating for brain aldehyde dehydrogenase and that the reduction of ethanol consumption by UChB rats may be the consequence of a change in the brain redox state, rather than the local level of acetaldehyde. PMID- 20575786 TI - Relationship between HIV-1 viral load and continued drug use in untreated infected injection drug users. AB - The role of continued drug use in development of AIDS has been investigated, using mainly CD4(+) cells as outcome variable. The objective of this study was to verify whether continued drug use can influence HIV-1 plasma viral load.We used cross-sectional enrolment data of the HIV-infected IDUs cohort study Manif 2000 (October 1995-October 1996), recruiting patients in hospital departments of Marseilles, Nice and Paris suburbs. To minimize biases due to differential access to health care, only patients receiving outpatient care for at least 2 years but with no antiretroviral treatment were selected for analysis (n = 108). Available information regarding clinical and laboratory information from medical records and clinical examination as well as drug use and HIV-related risk practices were obtained by a face-to-face and a self-administered questionnaire. Patients denying recent heroin injection were cross-validated by a serological assay to detect morphine. Forty-two patients (39%) reported recent heroin injection; among those denying recent use (n=66), eight (positive for serum morphine assay) were re-classified as IDUs. A difference of 0.35 log in viral load was observed between active and ex-IDUs which increases (0.6 log, p=0.03) in those who have been using drugs for 10 years or more.This result persisted when adjusted for CD4(+) counts, clinical stage or years since diagnosis. Continued drug use may have a significant but limited impact on HIV viral load only in patients with a longer history of drug use. Consequences of persisting drug use on long-term progression to AIDS has to be investigated further. PMID- 20575787 TI - Lack of association of the dopamine D4 receptor gene polymorphism with alcoholism in a Brazilian population. AB - The dopaminergic system has been implicated in alcoholism, but most of the past investigations concentrated on the dopamine D2 receptor (DRD2), with conflicting results. The dopamine D4 receptor gene (DRD4) is in the same class as DRD2, but presents different pharmacological properties. This gene has an expressed highly variable 48 base pair (bp) tandem repeat polymorphism (VNTR), which could be of functional relevance.We screened 100 Caucasians and 100 Afro-Brazilians to determine the allele distribution of this polymorphism in a southern Brazilian population. The allele frequencies observed are significantly different from those described in the literature except when Afro-Brazilians and African Bantus are compared. A group of 136 male alcoholics, classified according to DSM-III-R criteria for alcohol dependence, was also ascertained. The results of the association study were negative for comparisons between white and black alcoholics and controls, and no association was disclosed when either subtypes of alcoholics and different aspects of this condition were considered. These results, together with those available in the literature for other ethnic groups, suggest a minor role, if any, of the DRD4 gene in the susceptibility to alcoholism. PMID- 20575788 TI - Biological markers as indicators for relapse in alcohol-dependent patients. AB - Although biological markers such as carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT) and mean corpuscular volume (MCV) have been used as indicators for heavy alcohol consumption and alcoholism little information is available on the utitlity of these markers in detecting relapses. In this study the value of the biological markers CDT, GGT and MCV was examined in monitoring an outpatient treatment programme for alcohol-dependent patients. In 163 male alcoholic patients CDT, GGT and mean corpuscular volume (MCV) were assayed at the beginning and after 6 months during the outpatient programme. All markers distingushed between relapsers and abstainers (p<0.01). The sensitivity for relapses was 55% for CDT, 50% for GGT and 20% for MCV. Combining all markers the sensitivity could be enhanced to 85%, with only a little loss of specificity (85%). The highest positive predictive value was 73% for CDT used as a single marker. The negative predictive value (CDT 93%, GGT 92%, MCV 88%) and the diagnostic efficiency (CDT 91%, GGT 87%, MCV 85%) of all markers were very high. These results indicate that CDT is the most efficient marker for alcohol relapses, followed by GGT. MCV seems to be a marker of second choice. PMID- 20575789 TI - Catalase as a regulator of the propensity to ingest alcohol in genetically determined acatalasemic individuals from Israel. AB - Direct descendants of an individual residing in Israel, who was diagnosed in the 1960s with a genetic deficiency in catalase, were examined for their propensity to consume alcohol.These individuals were found to possess a lower level of catalase activity compared to that of a group of matched controls with the same ethnic background.While no differences were observed in the propensity to drink alcohol between the two groups, the catalase deficient individuals did show a significant positive correlation between catalase activity and alcohol drinking behaviour as measured by Q-value. No such relationship was observed in the matched controls.The findings suggest that the apparent acatalasemia in the experimental subjects may act as a limiting factor for these individuals and that catalase may play an important role in regulating alcohol drinking behaviour. These results are consistent with previous animal and human studies which suggest that catalase, via its ability to produce acetaldehyde through the metabolism of ethanol, may have a regulatory role in the propensity to drink alcohol. PMID- 20575791 TI - Society for the study of addiction. PMID- 20575790 TI - Effects of alcohol on respiratory variables in normal humans. AB - The study is designed to clarify the effect of low doses of alcohol on respiratory variables in air breathing normal subjects. Each subject was given an initial loading dose of alcohol (0.270 g/kg) followed, half an hour later, by a second dose (0.135 g/kg). Blood alcohol increased to a mean value of 52.0 +/- 3.0 (SEM) mg/100 ml at 1 hour. Resting ventilation increased significantly from a mean value of 6.25 +/- 0.41 litres min(-1) to 7.20 +/- 0.31 litres min(-1) 1 hour after alcohol (p= 0.025). Mean inspiratory flow was also increased (p= 0.045). End-tidal PCO2 (PET CO2) showed a highly significant fall (1.87 +/- 0.35 mm Hg; p < 0.001) without a significant change in CO2 production rate (p > 0.05). PET CO2 variability (100 x SD/mean) was low (mean 2.4%) and unaffected by alcohol. The longest end-expiratory pauses (apnoeas) observed for each subject were shortened significantly by alcohol (1.030 +/- 0.194 s and 0.690 +/- 0.138 s; p = 0.01). Moderate doses of alcohol in normal subjects, therefore lower PET CO2 and shorten end-expiratory pauses (apnoeic periods) but do not affect PET CO2 variability. PMID- 20575793 TI - Alcohol-thiamine interactions: an update on the pathogenesis of Wernicke encephalopathy. AB - Wernicke encephalopathy is a neurological disorder commonly observed in chronic alcohol abuse, in patients with AIDS, and in other conditions of compromised nutritional status. The underlying cause of the disorder is thiamine deficiency. The present review highlights data focusing on alcohol-thiamine interactions and their relationship to the pathogenesis of Wernicke encephalopathy. Recent findings on the effects of alcohol on thiamine absorption and storage and on thiamine phosphorylation to the enzyme co-factor form (thiamine diphosphate) are discussed with regard to the postulated "biochemical lesion" of Wernicke encephalopathy. Also discussed are new findings on the molecular genetics of the thiamine-dependent enzyme transketolase in patients with Wernicke encephalopathy. A discussion of the hypotheses regarding the mechanisms underlying the phenomenon of selective neuronal cell death observed in this disorder including cerebral energy deficit, focal lactic acidosis, glutamate excitotoxicity, increased expression of immediate-early genes, free radicals and perturbations of the blood brain barrier are presented. Finally, the possible role of thiamine deficiency in alcoholic peripheral neuropathy is reviewed. PMID- 20575794 TI - Involvement of the corticostriatal glutamatergic pathway in ethanol-induced ascorbic acid release in rat striatum. AB - The mechanism of ethanol-induced ascorbic acid (AA) release in striatum is not well understood. In the present work, the possible involvement of NMDA receptors in the corticostriatal pathway was studied by microdialysis coupled to high performance liquid chromatography with electrochemical detection. Ethanol (3.0 g/kg i.p.) stimulated significant striatal AA release to more than 200% above the baseline. This effect of ethanol could be partially antagonized by amantadine, a non-selective NMDA receptor antagonist and dopamine releaser, at a dose of 200 mg/kg i.p. and significantly antagonized by MK-801, a non-competitive NMDA receptor antagonist, at the doses of 0.5 and 1.0 mg/kg i.p. Furthermore, deafferentation of the glutamatergic projection from cortex to striatum by undercutting the prefrontal cortex completely eliminated ethanol-induced AA release in rat striatum. The basal level of AA in striatum could only be reduced by high doses of MK-801, but not by low doses of MK-801, amantadine or decortication. The results further confirm that NMDA receptors are involved in ethanol-induced AA release and provide the first evidence for the necessity of the activation of corticostriatal glutamatergic pathway in ethanol-induced AA release in rat striatum. PMID- 20575795 TI - Metabolism of drugs of abuse by cytochromes P450. AB - Studies of most drugs of abuse utilize in vivo animal experimentation so that the responses measured reflect the pharmacokinetics of the administered drug as well as its pharmacodynamics. These drugs are generally lipid soluble chemicals and their elimination is dependent on metabolism, so an understanding of this process is critical to the interpretation of responses. This review summarizes the interaction between drugs of abuse and cytochromes P450, the oxidative enzymes that catalyze the first step of the metabolic process. Although they process their substrates by a common chemical mechanism, these enzymes differ markedly in their regulation, i.e. induction and inhibition, their substrate selectivities, the metabolites they generate and their relative concentration in different species. The activity of an enzyme catalyzing a specific metabolic reaction can be altered by prior xenobiotic exposure, by its genetics and by a co-administered drug, so that the pharmacokinetics of the drug under study can vary with the history of the individual subject. These issues are obviously important in human studies so, when possible, the relevant human enzymes involved in the processes described have been identified. PMID- 20575796 TI - Preventing disulfiram hepatitis in alcohol abusers: inappropriate guidelines and the significance of nickel allergy. AB - Disulfiram hepatitis, although sometimes fatal, is a very rare complication of alcoholism treatment. A disproportionate number of cases are associated with disulfiram treatment for nickel allergy and unrecognized nickel sensitivity may partly explain the surprisingly high proportion of female victims- about 60%. US guidelines formulated in 1988 suggest that alcoholic patients should not be started on disulfiram unless liver toxicity tests have been done and, if elevated, returned to normal. This advice is unsound and contrasts with medical attitudes to the prevention of other rare side effects. It has led to significant delays in starting treatment which are probably much more hazardous than the very slight risks of hepatotoxicity. We recommend that the guidelines be modified in favour of an approach which emphasizes the education of patients and their carers and clinical rather than laboratory monitoring. PMID- 20575797 TI - Differences in propensity for drinking alcohol are reflected in subunit- and region-specific GABA(A) receptor levels. AB - Enhancement of GABA(A) receptor activity within certain discrete brain areas can elicit increased ethanol consumption, supporting a regionally specific role for GABAergic mechanisms in modulating ethanol reinforcement. The present study investigated if rats, which were in the highest (HES) or lowest (LES) 15th percentile of ethanol self-administration, had different GABA(A) receptor levels. MaleWistar rats (n=30) were trained to self-administer ethanol for 8 weeks followed by assessment of GABA(A) receptor mRNAs. In the last operant session the HES rats (4/group) were consuming significantly more ethanol than the LES rats (1.31+/--0.31 g/kg versus 0.02+/-0.02 g/kg; p<0.001). Significant GABA(A) receptor mRNA differences were found between the groups, which were subunit- and brain region-specific, with higher mRNA levels in the HES rats in the dorsal raphe (alpha2, alpha3, gamma1), medial raphe (alpha3, alpha, beta1, beta3, gamma1), cerebellum (alpha1, alpha6, beta3, gamma2long) and hippocampus (beta1, beta3, gamma1 and gamma2long). The elevated cerebellum alpha1 mRNA level in the HES rats was confirmed using Western blotting (mean density units +/-SEM; LES rats 0.460 +/-0.005 versus HES rats 0.610 +/- 0.006, p=0.03). These data suggest that the differences in GABA receptors were due either to the different propensities of the groups to consume ethanol or were caused by their differing ethanol exposure. PMID- 20575798 TI - Effect of bromocriptine on acute ethanol tolerance in UChB rats. AB - It has been suggested that a higher capacity to develop acute tolerance during a single dose of ethanol may promote higher ethanol consumption in alcohol preferring rodents. Several studies have shown that the dopaminergic system may be involved in voluntary ethanol consumption. In the present paper we studied the effect of bromocriptine, a dopaminergic agonist drug, that is known to reduce voluntary consumption of ethanol, on acute tolerance in high (UChB) ethanol consumer rats. Acute tolerance was evaluated in bromocriptine and saline-treated rats by motor impairment induced by a subnarcotic dose of ethanol of 2.3 g/kg IP using a modified tilting plane test. Results showed a highly significant positive correlation between acute tolerance and the voluntary ethanol consumption by the rat. Bromocriptine treatment decreased ethanol consumption and also decreased acute tolerance development. This adds further support to the postulate that the acquisition of acute tolerance to ethanol may promote increased alcohol consumption. Moreover, these results also suggest that dopaminergic receptors involved in ethanol voluntary consumption may also be in acute tolerance development. PMID- 20575799 TI - Association analysis of a PAX-6 gene promoter-associated polymorphic repeat with alcohol dependence. AB - The human paired box-containing gene PAX-6 participates in the development and plasticity of the brain including the limbic system, the neural system that plays a crucial role in reward processes. We have reported recently a polymorphic dinucleotide repeat sequence with the structure (AC)m(AG)n, which is located approximately 1 kb upstream of the transcription initiation site associated with promoter B and confers allelic variation of PAX-6 expression in the human brain. In the present association study we tested whether length variation of PAX-6 gene linked polymorphic region (PAX-6 LPR) influences susceptibility to alcohol dependence.The repeat length of the PAX-6 LPR was assessed in 354 control subjects and 328 alcohol-dependent patients, including four subgroups with a presumed substantial genetic predisposition: (a) with a history of withdrawal complications (n=100); (b) with a history of parental alcoholism (n=115); (c) with early onset (n=67) and (d) with dissocial personality disorders (n=54). Allelic distribution of the PAX-6 LPR did not differ significantly between the controls and the entire group of alcohol-dependent patients chi2=0.015, df 1, p=0.904), or any of the subgroups of patients with severe alcoholism. Our results do not provide evidence that length variation of the PAX-6 LPR contributes to the pathogenesis of alcohol dependence. PMID- 20575800 TI - The FAS Screen: a rapid screening tool for fetal alcohol syndrome. AB - Fetal alcohol syndrome (FAS) is an important cause of mental retardation and developmental disabilities. A population based screening tool would allow for early diagnosis and entry into intervention programs. The aim of the study was to develop a brief screening tool for use in population-based settings to improve the identification of children with FAS. The FAS Screen was developed and tested in six sites. These were sites that served children and all were located in North Dakota. Screening was completed on 1013 children, 65 were found to have a positive screening score and were referred for further investigation. Forty were seen for evaluation by a medical geneticist and six were diagnosed with FAS. The estimated values for the screening tool were: specificity 94.1%, sensitivity 100%, positive predictive value 9.1% and negative predictive value 100%. The cost of screening was $13.00 per child and the cost per case identified was $4,100. The FAS Screen is a brief screening test with acceptable performance characteristics and is cost effective. PMID- 20575801 TI - Electrocardiographic abnormalities during recovery from ultra-short opiate detoxification. AB - The aim of this study was to detect electrocardiographic abnormalities during recovery from ultra-short opiate detoxification, using a retrospective study design conducted at a university hospital. Twenty-two consecutive patients (mean+/-SD, age 30.0+/-6.3 years) receiving daily oral methadone underwent ultrashort opiate detoxification under general anaesthesia. In the post anaesthetic stages they received oral clonidine and naltrexone, and in some cases trimipramine was dispensed. Heart rate, rate-corrected QT interval (msec) and repolarization abnormalities of 12-lead electrocardiographic recordings before and after detoxification were examined. The serum electrolyte concentrations (mmol/l) including Na+, K+ and Ca2+ were assessed. Eighty-one ECGs were evaluated in total. Compared to the initial values, heart rate was significantly lowered in the first two tracings after detoxification (median values 60.0/min. vs. 52,5/min; p=0.0006). The lowest heart rate measured after detoxification was 44/min. The cQT interval was significantly lengthened (median value 420 msec vs. 453 msec after detoxification). In 16 tracings (20%) taken from 10 patients (45%) cQT rose above 460 msec and in two tracings (2%) it topped 500 msec. Modest hypokalaemia (2.9-3.5 mmol/l) was linked to cQT prolongation (460 msec) in 10 ECG tracings. Spearman's correlation coefficient indicated that prolonged cQT intervals correlated with decreased potassium values. Twelve tracings (15%) taken from 10 patients (45%) after detoxification showed T-wave inversion and in two cases sinus rhythm was turned into a rhythm arising from the atrioventricular node. Serum potassium was significantly lowered (median values 4.3 v.s 3.8 mmol/l, p=0.0001). The Ca2+ concentration fell significantly (2.4 vs. 2.2 mmol/l, p=0.0001) but not below the normal range. It was concluded that ultra-short opiate detoxification carries the risk of QT prolongation and bradycardia. These side effects are reversible and can be explained by hypokalaemia and clonidine medication, the effects of which might reinforce each other. To avoid arrhythmic complications, ECG tracings should be carried out regularly during recovery, i.e. at least daily, for a span of 3 days after discharge from the intensive care unit. PMID- 20575802 TI - Central pontine myelinolysis in a normonatraemic alcoholic patient. AB - Central pontine myelinolysis (CPM) is a rare disease which has been associated with hyponatraemia and its rapid correction. We describe a malnourished 32-year old alcohol-dependent woman suffering from an infection who had developed CPM without any known prior derangement in serum electrolytes or its iatrogenic correction. Computerized tomography (CT) and magnetic resonance imaging (MRI) played an important role in the diagnosis. Even when an electrolyte derangement is absent, alcoholism, malnourishment and infection should be considered as important possible aetiological factors of CPM. PMID- 20575804 TI - Erratum. PMID- 20575805 TI - Alcohol usage in sport and exercise. AB - In this review we consider some of the acute and chronic effects of alcohol on human exercise and sport performance. The 1982 position stand of the American College of Sport Medicine on the use of alcohol in sport emphasized that there was little benefit for an athlete. Subsequent literature continues to demonstrate that there are adverse effects on performance. However, the literature is often confusing and disparate. We will attempt to explain the effects and speculate on the possible mechanisms. We divide the review into acute and chronic metabolic and physiological effects of alcohol on exercise performance, primarily in humans. We also review the epidemiological evidence of the associations between alcohol use and problem alcohol behaviors in various athletic groups. Finally, we review the limited data on the effectiveness of exercise therapy in the treatment of alcohol dependent patients. In spite of scientific evidence that alcohol use is, in general, detrimental (or of no benefit) to sport (exercise) performance, alcohol continues to be used by athletes both on a chronic basis and even immediately prior to sports participation. There is some encouraging but limited evidence that student-athlete alcohol use is decreasing and exercise can be effective as part of alcohol rehabilitation. PMID- 20575806 TI - Allocating livers to substance and alcohol misusers. AB - The success of liver transplantation for the treatment of patients with end-stage liver disease has resulted in a widening gap between the number of potential recipients and the numbers of grafts available. Allocation of these scarce resources to people who have developed liver failure as a consequence of their own and often illegal behaviour has attracted much controversy. For patients with alcoholic liver disease, there is relatively little evidence that many patients return to a damaging pattern of alcohol consumption and, at least in the short term, the outcome is no different compared with patients grafted for other causes of cirrhosis. There are well-validated markers which predict abstinence. For abusers of other substances, there is relatively little experience. Of concern is the variation between the priority-setting by the medical profession and the general public. The latter, who, in the UK, can be considered as providers of the donated organs and pay for the costs of the procedure, tend to rate patients with alcoholic liver disease and who have drug or substance abuse at a lower priority than those who develop liver failure from other causes. These differences need further debate and resolution. PMID- 20575807 TI - Regulation of opioid receptors by opioid antagonists: implications for rapid opioid detoxification. AB - Opioid receptor antagonists have long been used in the diagnosis of opioid dependence and in the treatment of both opioid overdose and addiction. More recently they have been used in rapid opioid detoxification, a technique which has generated much ethical and scientific controversy. Because of this, the present review aims to integrate and summarize the current state of knowledge on adaptational changes to opioid systems as a result of antagonist administration. It is generally accepted that chronic treatment with an opioid antagonist results in opioid receptor upregulation. However, the mechanism(s) underlying this resultant opioid supersensitivity remain unresolved. In addition, there is not yet consensus regarding whether changes in opioid receptor number are directly responsible for the functional changes observed after chronic opioid antagonist treatment. Moreover, changes in opioid receptor number and sensitivity to opioid agonists and antagonists after chronic opioid antagonist treatment are dependent on dosing regimes as well as the kinetic properties of the antagonist itself. The role of these variables is appraised critically given the implication that an opioid antagonist can enhance functional responses. For example, such responses are an important consideration in the use of opioids because of possible adverse outcomes, such as overdose, after cessation of administration. Based on the literature discussed in this review it is concluded that caution is essential in the use of opioid antagonists for rapid opioid detoxification. PMID- 20575808 TI - Polymorphism of dopamine D2 and D4 receptor genes and Slavic-surnamed alcoholic patients. AB - The association between alcoholism and the Taq1 "A" and "B" polymorphic alleles at the DRD2 gene and 48-bp tandem repeat in exon 3 of dopamine D4 receptor (DRD4) gene in 42 unrelated Slavic-surnamed patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (chi2= 3.45, p < 0.001 and chi2)= 3.97, p < 0.001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (chi2= 3.33, p < 0.001).The results of association analysis for both the Taq1 "B" and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7-repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (chi2= 3.42, p < 0.01).The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general.The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism. PMID- 20575809 TI - Cortical metabolite alterations in abstinent cocaine and cocaine/alcohol dependent subjects: proton magnetic resonance spectroscopic imaging. AB - Chronic abuse of cocaine or alcohol is associated with structural, neuropathological and cognitive impairments that have been documented extensively. Little is known, however, about neurobiochemical changes in chronic substance abusers.We performed MRI and multi-slice brain proton magnetic resonance spectroscopic imaging (MRSI) to assess neuronal viability (via N acetylaspartate (NAA)) and white matter metabolite status in 22 4-months abstinent individuals dependent on crack cocaine only and on both crack cocaine and alcohol. Compared to 11 non-dependent controls we found (1) significantly lower NAA measures in the dorsolateral prefrontal cortex of the combined cocaine dependent groups; (2) comparable spatial distribution and magnitude of these NAA effects for both cocaine-dependent groups; (3) higher choline-containing metabolites in frontal white matter of individuals dependent on both cocaine and alcohol; (4) absence of brain atrophy in both abstinent cocaine-dependent samples; and (5) partial recovery from prefrontal cortical NAA loss, primarily with abstinence from alcohol. The MRSI findings suggest preferential neuronal damage to the frontal cortex of both cocaine-dependent samples and gliosis in frontal white matter of individuals dependent on both alcohol and cocaine, conditions that persist for more than 4 months of abstinence. PMID- 20575810 TI - Analysis of opiates and cocaine by RIA and GC-MS: distribution of their metabolites in urine and hair from drug addicts. AB - Two analytical techniques (RIA and GC-MS) were used for the simultaneous identification and determination of heroin, cocaine and their metabolites in the urine and hair of 200 drug addicts. Opiates tests were positive in 182 hair samples and 145 urine samples, whereas cocaine tests were positive in 173 hair samples and in 63 urine samples. Drug content of hair, as determined by RIA, varied over the ranges of 0-30 ng/mg (opiates) and 0-924 ng/mg (cocaine). Metabolite distribution was studied by GC-MS in samples taken from 50 individuals. Tests revealed 6-monoacetylmorphine to be ubiquitous in hair and morphine to be the major component in urine. Cocaine was found to invariably occur at higher concentrations than its metabolites in hair with the opposite result in urine. PMID- 20575811 TI - Effects of oral ethanol on end-tidal CO2tension in patients misusing alcohol. AB - This study examines the effect of oral ethanol ingestion on P(et)CO2 and other respiratory variables in alcohol-misusing subjects. Twelve patients were given a loading dose of alcohol (0.270 g/kg) followed by a second dose (0.135 g/kg) half an hour later, increasing blood alcohol to a mean of 82.0 +/- 10.3 (SEM) mg/100 ml at 1 hour. Five patients were classified as hazardous drinkers with evidence of mild alcohol dependence but no toxicity (Severity of Alcohol Dependency (SADQ) score < 15/60; serum carbohydrate-deficient transferrin < 6%). These patients showed a significant fall in mean end-tidal PCO2 (P(et)CO2) on alcohol (2.08 +/- 0.61 mm Hg; p = 0.027) with slightly increased ventilation (1.76 +/- 0.94 1 min( 1), p = 0.14); responses similar to those previously reported for normal subjects. Seven patients had evidence of moderate alcohol dependency and/or recent use (SADQ > 15/60; CDT > 6%). In these patients P et CO2 did not fall after alcohol challenge (mean change + 0.61 mm Hg; p > 0.30). There were significant correlations between the changes in P et CO2 and CDT (n = 12; r(s)= 0.66, p = 0.019) and SADQ (n = 11; r(s)= 0.688, p = 0.019). The results show that P(et)CO2 control is abnormal in the alcohol dependency syndrome. PMID- 20575812 TI - Encounters with aggressive conspecifics enhance the locomotor-activating effects of cocaine in the rat. AB - Evidence suggests that stress enhances the behavioural actions of cocaine in the rat. Paradoxically, however, encounters with aggressive conspecifics lead to a pattern of cocaine self-administration indicative of a reduced functional impact of the drug. Hence, we examined the effects of aggressive encounters on another behavioural measure-locomotor activity. Encounters between Lister Hooded rats and rats of the aggressive Tryon Maze Dull strain significantly enhanced the locomotor-activating effects of cocaine (20 mg/kg) in the Lister Hooded rats. The results suggest that the discrepant findings derived from self-administration studies are a property of the paradigm rather than a property of the stressor. PMID- 20575813 TI - Effect of low doses of ethanol on spontaneous locomotor activity in UChB and UChA rats. AB - The effects of low to moderate doses of ethanol on spontaneous locomotor activity were studied in the selectively bred high-ethanol drinking (UChB) and the low ethanol drinking (UChA) strain of rats. Alcohol-naive rats had food and water available ad libitum, although food was removed 24 hours before and during activity testing. After an injection of c.15 M NaCl or ethanol (0.25-1.0 g/kg), spontaneous locomotor activity was monitored every 5 minutes for 20 minutes in an open field apparatus. The UChB rats exhibited increased locomotor activity after doses of 0.25 and 0.50 g/kg of ethanol, while UChA rats failed to show increased locomotor activity at any ethanol dose. Moreover, the UChA rats appeared to be more sensitive to the sedating effects of 1.0 g/kg of ethanol than the UChB rats. These differences were not the result of different brain-blood alcohol levels. Ethanol intakes by the UChB and UChA rats determined at the conclusion of activity testing averaged 5.0 +/- 0.5 and 1.9 +/- 0.4 g/kg/day, respectively. The data suggest that ethanol-induced locomotor stimulation may be associated with ethanol preference and that hyperactivity may be an expression of the positive reinforcing effect of ethanol in UChB rats. PMID- 20575814 TI - Phagocytosis of the protozoon Tetrahymena pyriformis as an endpoint in the estimation of cocaine salt and cocaine freebase toxicity. AB - Cells of the ciliated protozoon Tetrahymena pyriformis strain W, grown in a peptone-yeast medium, usually contain many phagocytic vacuoles. The phagocytic activity of this protozoon was studied in vivo using heat-inactivated yeast stained with carmine after exposing the cultures for 1 hour to different doses of cocaine hydrochloride or cocaine freebase (crack) (0.5, 1 or 2 mg/100 ml of protozoan culture).The number of vacuoles formed indicated the phagocytic activity. Cocaine hydrochloride and crack caused a decrease of the phagocytic activity of the protozoon (p < 0.05) when compared to the control cultures. Furthermore, the two chemical forms of cocaine, salt and free-base respectively, caused quantitatively different effects on the phagocytic activity. Crack produced an extensive decrease in phagocytosis, compared to equal concentrations of cocaine hydrochloride. These results suggest a possible relationship between cocaine abuse and the suppression of phagocytosis that may contribute to the impairment of immunity in drug misusers. PMID- 20575816 TI - Biological phenotypes associated with individuals at high risk for developing alcohol-related disorders: Part 1. AB - This article reviews the results of studies concerning particular classes of biological phenotypes that may have relevance for alcohol dependence. Broadly defined, these classes include brain neurotransmitter systems and neuroelectric potentials. Evidence is presented concerning genotypic variation in alcoholics and high-risk relatives suggesting that the etiology of alcoholism and other addictive diseases is mediated in part through suboptimal neurotransmitter functioning. Research opportunities are offered with respect to specific candidate genes that have been cloned from these neurotransmitter systems that could be most fully utilized in family-based genetic analyses. Additional evidence is offered, suggesting that characteristics of particular neuroelectric potentials (e.g. the amplitude of the P300 component of the event-related potential) may provide another dimension of potential markers that could be used to identify children at risk. Finally, methodological considerations specific to high risk studies are discussed. Among these are the need to include a plan for studying more severe cases of alcohol dependence that are relatively uncomplicated by other major psychiatric disorders. Plans for long-term follow-up of children at highest risk for developing the disorder should also be included. Multiple domains of inquiry should not be viewed as "unfocused" but rather as an economical means for utilizing highly characterized samples of individuals meeting rigorous research criteria. PMID- 20575817 TI - Biological phenotypes associated with individuals at high risk for developing alcohol-related disorders. Part 2. AB - This paper reviews comparisons of populations at higher and lower risk for alcoholism on biological phenotypes. The results of studies must be considered in the context of the research methods used including the need for large, carefully defined samples and longitudinal designs. Comparisons of children of alcoholics and controls have revealed potentially important differences on level of response to alcohol, cognitive attributes and differences in alcohol-metabolizing and other enzyme systems responsible for various aspects of the body's reaction to alcohol. Many opportunities for future research in this area exist, including large-scale, longitudinal studies that simultaneously evaluate multiple domains of influence, and searches for candidate genes or other biological material that will simplify procedures and increase the accuracy of measurement. PMID- 20575818 TI - Neuropharmacology and therapeutic potential of cannabinoids. AB - Mammalian tissues contain at least two types of cannabinoid receptor, CB1, found mainly on neurones and CB2, found mainly in immune cells. Endogenous ligands for these receptors have also been identified. These endocannabinoids and their receptors constitute the endogenous cannabinoid system. Two cannabinoid receptor agonists, Delta9-tetrahydrocannabinol and nabilone, are used clinically as anti emetics or to boost appetite. Additional therapeutic uses of cannabinoids may include the suppression of some multiple sclerosis and spinal injury symptoms, the management of pain, bronchial asthma and glaucoma, and the prevention of neurotoxicity. There are also potential clinical applications for CB1 receptor antagonists, in the management of acute schizophrenia and cognitive/memory dysfunctions and as appetite suppressants. Future research is likely to be directed at characterizing the endogenous cannabinoid system more completely, at obtaining more conclusive clinical data about cannabinoids with regard to both beneficial and adverse effects, at developing improved cannabinoid formulations and modes of administration for use in the clinic and at devising clinical strategies for separating out the sought-after effects of CB1 receptor agonists from their psychotropic and other unwanted effects. PMID- 20575819 TI - Background genotype modulates the effects of gamma-PKC on the development of rapid tolerance to ethanol-induced hypothermia. AB - The role of gamma-PKC in initial sensitivity and in the development of rapid tolerance to the hypothermic effects of ethanol were investigated in gamma-PKC null mutant mice. Effects of the single gene mutation were evaluated on three different genetic backgrounds. Null mutants from a C57BL/6J X 129/SvJ mixed genetic background failed to develop rapid tolerance after 4 days of i.p. ethanol injections. However, when the null mutation was introgressed onto a C57BL/6J background for six generations to create a congenic line, the expression of rapid tolerance unexpectedly reoccurred in the null mutant mice. Subsequent outcrossing of the gamma-PKC null mutation to a C57BL/6J X 129/SvEvTac mixed background did not restore the no tolerance phenotype. These observations, taken together with similar results reported previously concerning the development of chronic tolerance to ethanol in these same genotypes, 1 indicate that the gene coding for gamma-PKC has pleiotropic effects in the expression of both rapid and chronic tolerance to ethanol-induced hypothermia. However, the impact of gamma-PKC is modulated by the background genotype. These results stress the necessity of understanding interactions with genetic background when interpreting the effects of single gene mutations on complex behavioral traits. PMID- 20575820 TI - Buprenorphine and carbamazepine as a treatment for detoxification of opiate addicts with multiple drug misuse: a pilot study. AB - The growing tendency of opioid addicts to misuse multiple other drugs leads to the investigation of new pharmacostrategies to prevent patients from suffering life-threatening complications and minimize the withdrawal symptoms. The short term efficacy of a 10-day low-dose buprenorphine/19-day carbamazepine regime (n = 15) to a 14-day oxazepam/19-day carbamazepine regime (n = 12) in an open-labelled 21-day inpatient detoxification treatment was compared. Twenty-seven men and women dependent on opioids and misusing other drugs admitted to a detoxification unit were included in this protocol. Eighteen of 27 patients (67%) completed the study. Four non-completers (27%) received buprenorphine/carbamazepine (four of 15) and five non-completers (42%) were treated with oxazepam/carbamzepine (five of 12), but the difference in the dropout rate between the two treatment strategies was not significant.The buprenorphine/carbamazepine regime provided significantly more effective relief of withdrawal symptoms during the first week of treatment. No severe side effects occurred during treatment in both groups. The present study supports the hypothesis that buprenorphine/carbamazepine is more effective than oxazepam/carbamazepine in rapid opioid detoxification in patients with additional multiple drug misuse and both regimens were safe with no unexpected side effects. PMID- 20575821 TI - Reduced sensory and motor nerve conduction velocities in moderate drinkers. AB - The mechanism responsible for peripheral nerve dysfunction in chronic alcoholism has not been fully elucidated either in terms of its relationship to the quantity of alcohol consumed or to nutritional status. As part of a series of studies to address these issues, the effects of moderate drinking (60-90 g ethanol per day) or heavy drinking (> 100 g ethanol per day) on peripheral nervous function and thiamine status was measured in 73 patients admitted to a detoxification unit. Electromyographic evaluation revealed significant reductions in median and ulnar sensory and motor nerve conduction velocities in both moderate drinkers (n = 30) and heavy drinkers (n = 43) compared to age-matched controls. Twelve moderate drinkers and 25 heavy drinkers manifested clinical neurological signs of peripheral neuropathy. Thiamine deficiency, as revealed by erythrocyte transketolase activation assay, was detected in two moderate drinkers and seven heavy drinkers but was not significantly correlated with electromyographic alterations with the exception of ulnar nerves. These findings provide evidence for significant early peripheral nerve dysfunction in moderate drinkers and a possible contributory role of thiamine deficiency to the ulnar nerve conduction deficits. Whether deficits in other water-soluble vitamins or a direct neurotoxic effect of ethanol are implicated in alcoholic peripheral neuropathy awaits further studies. PMID- 20575822 TI - Osmotic effects of ethanol on lymphocytes. AB - The alterations in the immune system caused by ethanol appear to be a complex combination of direct and indirect effects. The role of ethanol as an osmolyte has previously been studied in this laboratory with rat splenocytes. In the present study the osmotic effects of ethanol were investigated in lymphocytes from human normal subjects and alcohol abusers. Mitogen-stimulated lymphocytes were cultured in vitro with ethanol in hyperosmotic isotonic or iso-osmotic hypotonic conditions. The former conditions mimic the physiological situation where ethanol increases osmolality in an electrolyte-balanced environment. Under these conditions, lymphocyte proliferation was unaffected. Ethanol addition in iso-osmotic hypotonic conditions, where there is electrolyte imbalance, was associated with inhibition of T-lymphocyte proliferation. Hyperosmotic hypertonic solutions in the absence of ethanol also resulted in inhibition of T-lymphocyte proliferation. Electron microscopy and measurement of cell viability and metabolic activity (lactate and ATP levels) indicated that the decreased proliferation associated with NaCl-induced hyperosmotic hypertonic conditions was at least partially attributable to cell death together with, and possibly caused by, detrimental effects on mitochondria. Conversely, decreased T-lymphocyte proliferation in iso-osmotic hypotonic high ethanol solutions, appeared not to be due to changes in cell viability, nor alterations to energy metabolism. It is proposed that ion fluxes involved in the maintenance of cell volume, in particular K + movement, may be important in facilitating normal lymphocyte proliferation in the presence of ethanol in pathological conditions associated with electrolyte imbalance. PMID- 20575823 TI - Cardiovascular and hormonal responses to hyperthermic stress in cocaine addicts after a long period of abstinence. AB - In order to study the effects of exposure to heat, cardiovascular and hormonal responses were measured in 10 male cocaine addicts (after 4 weeks and 1 year of abstinence) and in 10 normal men. Subjects sat for 30 minutes in a sauna room. Hormonal (ACTH, beta endorphin, (beta EP) met enkephalin (met-enk), prolactin (PRL), cortisol) and cardiovascular parameters (heart rate, systolic and diastolic blood pressure) were measured before and after heat exposure. Basal levels of ACTH, beta EP, Met-Enk and cortisol were similar in normal and in cocaine addicts, whereas plasma PRL values were higher in drug abusers after long term abstinence. All the examined hormones, with the exception of Met-Enk, were significantly raised in normal control subjects at the end of sauna. In contrast, no significant hormonal response to hyperthermia was observed in cocaine addicts either after 4 weeks and 1 year of abstinence. No changes were detected in heart rate and blood pressure in each group, indicating that the cardiovascular adaptive responses to hyperthermia in cocaine addicts was unaltered. The results of the present study provide evidence of an impairment of the hormonal response to hyperthermia in cocaine abusers. In conclusion, cocaine abuse produces alteration in the hypothalamic-pituitary function which persists after a long period of abstinence. PMID- 20575824 TI - Reduced [11C]flumazenil radioligand binding in the thalamus in alcoholics. AB - Positron emission tomography (PET) provides in vivo quantitative measurement of radioligand binding to central neuroreceptors. In this report we present the history and PET findings of the thalamic region in two patients with diagnosis of alcohol dependence using the radioligand [11C]flumazenil (Ro 15-1788), a benzodiazepine receptor antagonist. This abnormality in the thalamus may reflect an early alcohol-induced brain lesion or contribute to the development of alcoholism in some subjects. PMID- 20575826 TI - Alcohol-related diarrhea. AB - Abstract Alcohol generates a large caloric yield without supplying any essential nutrients; alcoholics may thus maintain body weight while suffering from malnutrition. In addition, diarrhea is a common complaint of both acute and chronic alcoholics. Here, we review the effects of alcohol on gastrointestinal morphology, function, its nervous system and motility. Acute morphological changes such as erosions, inflammatory cell infiltrations and microvascular changes are seen in the stomach and small intestine in acute alcoholics. In addition, atrophic gastritis, reduced villous height and decreased mucosal surface area of the small intestine have been described in chronic alcoholics. Acute administration of alcohol inhibits absorption of nutrients and fluids, and can stimulate secretion of water and electrolytes. Bacterial overgrowth in the proximal small intestine and decreased pancreatic secretions have been also described in chronic alcoholics. The well-known deleterious effects of alcohol on the central nervous system raise the possibility of similar acute and chronic effects of the enteric nervous system. Such effects could alter motility and transit. Indeed, esophageal dysmotility and delayed gastric emptying have been observed with high concentrations of alcohol in experimental studies and in chronic alcoholics. Small bowel motility and transit may be abnormal in both acute and chronic alcoholics, and colonic propulsive motility is increased after acute administration of alcohol. Any, or all, of these changes in gastrointestinal functions may contribute to diarrhea in acute binge drinkers and chronic alcoholics. Unfortunately, there is a lack of systematic studies of the pathophysiology of alcohol abuse, and an integrating concept of the diarrhea of alcoholics is still not possible. PMID- 20575827 TI - Screening for fetal alcohol syndrome: is it feasible and necessary? AB - The potential to utilize screening strategies to improve the identification and outcome of persons with fetal alcohol syndrome (FAS) is reviewed. FAS is a condition where screening and surveillance activities would be appropriate. Development of FAS screening and surveillance programs is encouraged because the disorder is expensive. People with FAS have poor outcomes as adults with less than 10% living independently. Several useful tools and models are available. Screening would improve ascertainment and prevalence estimates. Early identification could improve access to services and long term outcome, secondary disabilities and, by extension, excess disability in affected children could be decreased. Lastly, mothers who are at the highest risk to have additional children with FAS could be identified and offered treatment. While both screening and surveillance activities are discussed, the principle focus of this article is a review of the screening process. Two screening tools and several screening methodologies for FAS are available. Since no test will be appropriate in all settings, screening tests need to be selected depending on the setting and population of interest. Screening for FAS should be conducted in a variety of settings and in populations of both high and moderate risk. The results would also provide important data to influence public policy development and resource allocation. Appropriate evaluation of the efficacy, efficiency and effectiveness of FAS screening tools and methodologies would be important before utilization in screening programs. PMID- 20575828 TI - Autoantibodies in alcoholic liver disease. AB - Despite many decades of research, the reasons why only a relatively small proportion of individuals who consume excessive quantities of alcohol develop clinically significant liver disease remain unknown. The association with features of autoimmune diseases, including hypergammaglobulinaemia, circulating autoantibodies, inheritance of certain immunogenetic (HLA) markers and response to corticosteroid therapy in some patients has led to a persistent impression that altered immune regulation with a relative loss of self-tolerance underlies susceptibility to the development of the more severe forms of alcoholic liver disease (alcoholic hepatitis and/or cirrhosis). However, review of the data from the numerous studies that have been conducted over the past 30 years fails to reveal sufficiently convincing evidence that autoimmunity plays a primary role in alcohol-related liver damage. In particular, most of the wide range of circulating autoantibodies that have been reported in patients are found mainly at low titres, are not confined to those with severe liver injury, and are probably more likely to be a response to the hepatic insult than causally related to liver damage. Additionally, an association with various HLA phenotypes has not been confirmed by meta-analysis. Interpretation is complicated by evidence that alcohol may have direct effects on some components of the immune system but, if there is an immunogenetic basis for alcoholic liver disease, the present evidence suggests that this might be related more to cytokine gene polymorphisms than to a predisposition to autoimmunity per se. PMID- 20575829 TI - The inhibition of [3H] inositol 1,4,5-trisphosphate binding by Ca2+ is modified after long-term ethanol treatment and ethanol withdrawal. AB - We have analysed the influence of long-term ethanol exposure on the effect exerted by Ca2+ on the binding of tritiated inositol 1,4,5-trisphosphate to its receptors in rat cerebellar membranes. After 21 days of ethanol treatment the binding of the agonist was reduced in the absence of Ca2+. The decrease was due to reduction in B max without any alteration of K d. In membranes from control animals Ca2+ inhibited the binding of InsP3 in a dose-dependent manner by altering the affinity of the protein for the ligand. However, the inhibitory effect of Ca2+ was abolished following chronic ethanol exposure. Five days after withdrawing ethanol, the B max recovered to control values, but the inhibitory effect of Ca2+ was recovered at only 10 days after withdrawal. The results indicate that long-term ethanol exposure may have differential effects on the InsP3binding site and on the Ca2+ binding site, or alternatively on a Ca2+ related regulatory cycle. PMID- 20575830 TI - Apoptosis induction by phencyclidine in the brains of rats of different ages. AB - We examined whether acute administration of phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor-channel complex, can cause neuronal toxicity that is associated with apoptosis. Three- and 24-month-old rats were placed in locomotor activity chambers. PCP (50 mg/kg) or saline (0.15 M NaCl) were simultaneously administered to the treated and age-matched controls. After observing changes of locomotor activities, the animals were killed 24 h after treatment. The brains were processed for in situ analysis of apoptosis either by propidium iodide (PI) staining, or for the terminal dUTP nick-end labelling (TUNEL) method. The regional distribution of apoptotic nuclei was established using PI staining. Apoptosis was additionally confirmed and quantified by the TUNEL technique. PI and TUNEL staining revealed that PCP-mediated neurotoxicity in the prefrontal and enthorhinal cortices, the striatum and hippocampus was associated with a significant number of neurons exhibiting apoptotic morphology. We found that the total number of apoptotic cells was higher in the brains of 24 month-old rats. Compared to the respective controls the number of apoptotic cells was 3.8-fold greater in the cortex of old rats, followed by the striatum (three fold), and hippocampus (1.4-fold). Accordingly, we concluded that ageing was accompanied by DNA-damage that was most pronounced in the prefrontal cortical neurones. The most prominent elevation in the degree of apoptosis in the young treated compared to young-untreated rats was detected in the striatum. Comparison of the number of TUNEL-positive cells in treated-aged versus treated-young rats revealed that in all the examined regions of the brain PCP exerted a stronger apoptotic effect in younger animals. PMID- 20575831 TI - Evaluation of an allelic association of the serotonin 5-HT1B G681C polymorphism with antisocial alcoholism in the German population. AB - Our study tested whether an association of the 861C allele of the serotonin 5 HT1B gene (HTR1B) with antisocial alcoholism exists in the German population. The HTR1B G861C polymorphism was genotyped in 588 subjects of German descent, comprising 250 non-alcoholic controls and 338 alcohol-dependent subjects, of whom 56 exhibited a dissocial personality disorder (DSPD). The Tridimensional Personality Questionnaire was assessed in 109 alcohol-dependent males to explore an effect of the 861C allele to risk-taking behaviour. Our results revealed no evidence for an association of the 861C allele with antisocial alcoholism (p > 0.63). There were no significant differences in the personality traits, novelty seeking, harm avoidance and reward dependence between 46 male alcoholics carrying the 861C allele compared to those 63 alcoholics lacking it (p > 0.52). Our results do not provide evidence that the 861C allele contributes a substantial vulnerability effect to antisocial behavior in German alcohol-dependent subjects. PMID- 20575832 TI - A dependency syndrome related to areca nut use: some medical and psychological aspects among areca nut users in the Gujarat community in the UK. AB - Use of betel nut (areca nut) and its products is widespread, particularly in the Indo-Chinese continents, being the fourth most widely used substance after tobacco, alcohol and caffeine, affecting approximately 20% of the world's population. Betel nut, with or without admixed tobacco, is widely used among UK Indo-Asian immigrants, particularly Gujurate speakers. To date most research has concentrated on oral submucous fibrosis and malignancy. This paper reports detailed socio-demographic, clinical, laboratory and psychological studies in 11 current and former heavy betel nut users, referred by an Oral Medicine Unit in NW London. The patients, nine males, two females, had a high incidence of cardiovascular disease and truncal obesity. Laboratory investigations showed a high incidence of reduced serum B12 levels (4/9) and raised urinary cotinine levels (6/11), although none were current cigarette smokers. These findings are consistent with heavy usage of tobacco-areca combinations by this group. Routine biochemical and haematological investigations and clinical examination revealed no consistent abnormalities. Subjects had used areca for an average of 35 years with the mean age of first use being 13 years. Most subjects reported beneficial psychosocial effects. Ten subjects reported cessation withdrawal effects with the mean Severity of Dependence Score of 7.3. These findings are consistent with the existence of a dependency syndrome among those who use areca nut products. Further research is required to delineate the relative contributions of areca nut and tobacco to this clinical picture. Use of the areca nut, especially with tobacco, represents an area of health prevention among the UK minority populations that has, to date, been overlooked. PMID- 20575833 TI - Association analysis of polymorphisms in the MU opioid gene and heroin abuse in Chinese subjects. AB - We examined four polymorphisms in the MU opioid receptor gene in 282 Chinese heroin addicts from Sichuan Province, Southwest China and compared the allele and genotype frequencies to those in 258 normal controls from the same geographic region. Two of these polymorphisms (Ala6Val and Ser147Cys) were not polymorphic in the Chinese, with only Ala6 and Ser147 observed. The frequencies of the two other polymorphisms were significantly different from those observed in Caucasians, African Americans and Native Americans. The Asn40Asp and IVS2 + 691G/C polymorphisms did not differ significantly for allele (p= 0.16; p = 0.21), genotype (p= 0.32; p = 0.09) or haplotype frequencies (p= 0.24) between the Chinese heroin-addicted cases and normal controls. Similarly, we did not detect any association when the population was stratified by gender, route of administration (nasal inhalation and/or injection) and age-at-onset (above or below 25 years). This indicates that the MU opioid receptor is not likely to be a major genetic risk factor for heroin abuse in this population. PMID- 20575834 TI - Ascertainment of families for a linkage study of alcoholism. AB - Traditionally, researchers working in the field of genetics and alcoholism have used treatment centres and clinics to try and recruit suitable subjects for research purposes. The current study considered a diverse range of possible sources to recruit suitable families for a linkage study of alcoholism. These sources included the press, personal contacts and circular letters to alcohol treatment centres and members of the Substance Misuse Section of the Royal College of Psychiatrists. Only 9-14% of families contacted from any source were suitable for inclusion in the study, due to the strict selection criteria. Press contacts were found to be the most productive source of suitable families willing to participate in the study, accounting for over 50% of contacts and eventual subjects recruited. There appeared to be no bias in the affection status of subjects recruited from the different sources. For future genetic studies of alcoholism it might be worthwhile to utilize this source more fully. Reasons for exclusion from the study are also considered, with the most common reasons being non-co-operation and no family history. PMID- 20575835 TI - The acute influence of tobacco smoking on adhesion molecule expression on monocytes and neutrophils and on circulating adhesion molecule levels in vivo. AB - Soluble adhesion molecules have been reported as risk markers of a wide range of human diseases and specific adhesion molecules may play a direct role in pathological processes. Serum soluble intercellular adhesion molecule-1 (sICAM-1) is known to be significantly elevated in smokers compared to non-smokers. We examined the acute effects of smoking a standard 2R1 research cigarette on the serum concentration of sICAM-1 and other circulating adhesion molecules (sP selectin, sE-selectin, sL-selectin, sVCAM-1 and sPECAM-1) in heavy smokers (serum cotinine >/= 100 ng/ml), light smokers (serum cotinine 300 parent-offspring trios) to definitely corroborate or reject the findings from our case-control sample. PMID- 20575844 TI - Possible association between loudness dependence of auditory evoked potentials and tryptophan hydroxylase-alleles in alcoholics. AB - Abstract The serotonergic neurotransmission was suggested to play an important role in the aetiology of alcoholism. This study explores the association between tryptophan hydroxylase (TPH)-alleles and Loudness Dependence of Auditory Evoked N1/P2 Potentials (LDAEP). The TPH is the rate-limiting biosynthetic enzyme in serotonergic pathway. The LDAEP is one of the best validated non-invasive indicators for serotonergic neurotransmission. A sample of 54 alcoholics was recruited. N1/P2 potentials were evoked by five different sound intensities. A dipole source analysis using BESA (brain electric signal topography) was performed and intensity dependence was computed. The TPH intron 7 polymorphism was determined by using PCR in DNA samples. There was a weak but significant association between low LDAEP and the L-TPH allele. No influence from an individual's history of alcohol dependence or a positive family history of alcohol dependence on LDAEP was found. The weak but significant relationship found between L-TPH-allele and high serotonergic neurotransmission may contribute to a more detailed neurobiological characterization of alcohol dependents using functional and genetic parameters. PMID- 20575845 TI - Characteristics of Japanese alcoholics with inactive aldehyde dehydrogenase: clinical features of alcoholics with ALDH2*2. AB - Abstract In a person with inactive ALDH2 (ALDH2*2) the blood aldehyde concentration tends to rise faster and higher and there are flushing responses which are considered to be a restraint against excessive alcohol drinking. The subjects in this study comprised 71 Japanese alcoholics. Psychiatrists interviewed the patients concerning the clinical features. Alcoholics homozygous (n = 59) for ALDH2*1/ALDH2*1 (Group I) and those heterozygous (n = 12) for ALDH2*1/ALDH2*2 (Group II) were compared. Group II alcoholics included significantly more cases of guilt or personality disorder. These findings indicate that alcoholics with the ALDH2*2 genotype showed generally typical clinical features. PMID- 20575846 TI - Relevance of urinalysis monitoring of methadone maintenance patients: a clinical biological agreement on 41 patients. AB - Abstract This study evaluated the concordance of concomitant urinalysis and clinical assessments of drug abusers included in a methadone maintenance programme. The agreement between a clinical subjective score and an objective biological score, both measuring the evolution of illicit substance consumption over 12 months, was analysed. The clinical score, established by physicians and applied during patient interviews, was determined at entry into the programme and re-evaluated after 6 and 12 months. Forty-one patients were evaluated. The urinalysis score was based on regular screening of urine samples with the EMIT method. Agreement between the two scores was determined by using the kappa coefficient for each substance (opiates, benzodiazepines and cocaine) for each time-point. The calculated kappa coefficients showed poor agreement between the two scores, but could indicate the complementarity of these clinical and biological appraisals. Indeed, the urinalysis objectively detected change in drug use before the clinician. Thus, urinalysis monitoring should be considered as an additional and complementary biological procedure for patient follow-up by physicians. PMID- 20575847 TI - Ofloxacin causes false-positive immunoassay results for urine opiates. AB - Abstract Immunoassay drug screening tests are usually used as a control during methadone maintenance programmes, to check cleanliness of drugs during detoxification treatment and abstinence programmes. False-positive results can have catastrophic consequences for the patient, as shown in the case report. False-positive results were reported for opioids following ofloxacin or rifampicin and for LSD following mucolytic. Since inpatient and outpatient units usually employ an urine quick test (immunoassay), positive results should be checked with gas chromatography/mass spectroscopy (GC-MS) or high pressure liquid chromatography (HPLC) before conclusions from the positive urine screening results can be drawn. PMID- 20575848 TI - Preface: Recent advances of neurobiological basis of stimulant-induced sensitization. PMID- 20575849 TI - A role for glutamate transmission in addiction to psychostimulants. AB - Abstract Psychostimulant addiction results in the emergence of undesirable behaviors such as drug craving and paranoia. Using animal models of addiction the neurobiological substrates mediating these behaviors have been examined. Studies have focused on cellular adaptations within the motive circuit that contains the nucleus accumbens, ventral tegmental area, ventral pallidum and prefrontal cortex. While long-term alterations in dopamine transmission have been clearly characterized, more recent studies reveal that important neuroadaptations are also produced in glutamate transmission.This short review provides a description of these neuroadaptations and a discussion of how these psychostimulant-induced changes may synergize to elicit addiction-related behaviors. PMID- 20575850 TI - Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice. AB - Abstract Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to be associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn) superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male SwissWebster mice were treated with or without 7-nitroindazole (7-NI) along with METH (5 mg/kg,ip,q 3h x 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH-treated animals. 7-NI completely protected against the depletion of DA, and DAT in striatum. In follow-up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6JSV129) mice were treated with METH (5 mg/kg,ip, q 3h x 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10-20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT binding sites in the wild-type animals. Pre-exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH-induced neurotoxicity and behavioral sensitization. PMID- 20575851 TI - Increased sensitivity to stress associated with noradrenergic hyperactivity, involving dopaminergic hyperactivity in spontaneous recurrences in methamphetamine psychosis. AB - Abstract The study examined the significance of increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes in spontaneous recurrences of methamphetamine (MAP) psychosis (flashbacks). Plasma monoamine metabolite levels were assayed in the subjects: 19 flashbackers, 18 non flashbackers with a history of MAP psychosis and 37 controls. Monoaminergic values underwent a square-root transformation. All flashbackers had been exposed to stressful events plus MAP-induced fear-related psychotic symptoms (n = 11) or fear-related symptoms alone (n = 8). Factors triggering flashbacks met the DSM III-R criteria for mild psychosocial stressors. During flashbacks norepinephrine levels increased markedly and 3-methoxytyramine, which is indicative of dopaminergic activity, increased to a lesser extent. Among the flashbackers, 11 with a history of stressful events plus fear-related symptoms displayed further a small increase in 3-methoxytyramine levels. Thus, stressful events plus fear related symptoms, together with MAP use, may induce noradrenergic hyperactivity and some degree of dopaminergic hyperactivity in response to mild stressors. Increased sensitivity to stress associated with a predominance of noradrenergic over dopaminergic hyperactivity may be a precipitating factor in flashbacks. PMID- 20575852 TI - Molecular and regional targets of cocaine in primate brain: liberation from prosaic views. AB - Abstract The neurochemical processes underlying initial exposure to and reinforcing effects of cocaine are not fully understood. An enduring hypothesis of cocaine addiction is based on an underlying premise that dopamine is the acute mediator of the rewarding effects of cocaine and this nefarious role extends through each phase of addiction. Cocaine is an effective inhibitor of the dopamine transporter, thereby increasing extracellular dopamine levels. Euphoria is attributed to the cocaine-induced inundation of extracellular dopamine and the withdrawal and craving for cocaine after cessation of drug use are attributed to neuroadaptive processes to dampen dopaminergic transmission. Nevertheless, our understanding of the role of dopamine transporter blockade in cocaine addiction is not fully understood. The objectives of this laboratory are to investigate the primary targets of cocaine in the brain, those associated with the initial phase of cocaine use and that can provide leads for investigating neuroadaptive processes that may trigger addiction. Two prosaic views of the neurobiology of cocaine addiction are examined in this review. The first is based on the assumption that the dopamine transporter contributes significantly to the stimulant and reinforcing effects of cocaine, and focuses on how stimulant drugs of abuse such as cocaine bind to the dopamine transporter. We present evidence that the widespread assumption that dopamine transporter blockers require an amine nitrogen in their structure is incorrect as non-amines are effective blockers of transporters. The second prosaic view, based on the assumption that the dopamine transporter fulfills a paramount role in cocaine addiction, is assessed in view of mounting evidence that the transporter may not account for the full spectrum of cocaine's effects. Other targets of cocaine, which may be relevant to the acute and chronic effects of cocaine, are presented. PMID- 20575853 TI - Prior exposure to a behaviorally sensitizing regimen of d-methamphetamine does not alter the striatal dopaminergic damage induced by a neurotoxic regimen. AB - Abstract Repeated exposure to psychostimulant drugs such as d-methamphetamine (d METH) and cocaine can be associated with extremely long-lived changes in dopamine systems at the behavioral, cellular and molecular level. Sensitization or an enhanced response to drug exposure is one such change. Investigations of these phenomena at the cellular and molecular levels are being conducted in the hope that this will aid in understanding how such adaptations might contribute to drug addition. Repeated exposure to certain amphetamines can also result in damage to dopaminergic pathways. Although some of the same molecular adaptations and mechanisms are suspected to occur or play a role in the neurotoxic sequelae associated with psychostimulant exposure, there has been little attempt to examine the relationship among these phenomena. Here we utilized C57BL/6J female mice to examine whether exposure to a sensitizing regimen of d-METH would impact the degree of neural injury induced by a subsequent exposure to a neurotoxic regimen of the same psychostimulant. Every other day exposure to d-METH (1.0 or 2.0 mg/kg) for 11 days produced a behavioral sensitization, as evidenced by a significant increase in the degree of locomotor activity induced by each subsequent exposure to d-METH. Following a 5-day period of no drug exposure sensitized mice were given a neurotoxic regiment of d-METH (a total of four injections of 10.0 mg/kg, one every 2 hours) and striatal tissue examined 72 hours later. All groups, whether drug-naive or sensitized previously to d-METH, showed exactly the same degree of dopaminergic striatal damage induced by a neurotoxic regimen. This was evidenced by equivalent reductions in dopamine and elevations in GFAP protein, a marker of astrocytic response to injury, GFAP. The inability of a sensitizing regimen to either exacerbate or lessen the neurotoxic actions of the same compound suggests that the molecular and cellular control of these two aspects of psychostimulant exposure may differ. PMID- 20575854 TI - Chronic dopaminergic signaling in the basal ganglia: a damage perspective on kinases and fos-related antigens. AB - Abstract Specific protein phosphorylation pathways have been shown to play a role in cellular adaptation responses underlying addiction to psychostimulants such as methamphetamine and cocaine. Transcriptional regulation through fos-related antigens constitutes one element through which these dopaminergic agonists exert their persistent actions. In addition to their addictive properties, amphetamines are known to damage dopaminergic nerve terminals. Although not widely appreciated, protein phosphorylation cascades and fos-related antigens also may play a role in the neurotoxic actions of substituted amphetamines such as methamphetamine. Here we document the involvement of the dopaminoceptive phosphoprotein, DARPP-32, the fos-related antigen, FRA-2, and the growth associated protein kinase, MAP kinase, in the neurotoxic action of known dopaminergic neurotoxicants, including methamphetamine. The addictive and neurotoxic properties of psychostimulants may share some molecular signaling mechanisms. PMID- 20575856 TI - Gamma-hydroxybutyric acid in alcohol preference, dependence and withdrawal. AB - Gamma-hydroxybutyric acid (GHB) is an endogenous constituent of the mammalian brain, where it likely functions as a neurotransmitter or a neuromodulator. Its exogenous administration exerts a number of pharmacological effects, including reduction of intensity of alcohol withdrawal syndrome and alcohol consumption in both laboratory animals and human alcoholics.The clinical studies conducted to date, although often testing samples of limited size, feature GHB as an effective, well-tolerated and safe drug for the treatment of alcohol dependence. Behavioural data in rats suggest that GHB may produce alcohol-like effects. This similarity may explain why GHB produces positively reinforcing properties, being subsequently self-administered by rodents and sometimes abused by humans (although episodes of self-directed intake of GHB appear to be a limited phenomenon in alcoholics); in addition it provides support to the hypothesis that GHB constitutes for alcoholism a replacement therapy similar to methadone in heroin addiction. PMID- 20575857 TI - Alcohol genetics: will the promise be fulfilled? AB - Genetic research into alcohol-related problems has a long history, but only with the recent advent of molecular biological techniques does it seem poised to fulfill its promise. While such research might be thought to reinforce views of the inevitability and immutability of drinking problems, there have been bold promises of important developments in our understanding of the aetiology of alcohol misuse, as well as promises of innovations in prevention and treatment. A brief consideration of recent research, and of the possibilities that are now before us, reveals that the promise of increased understanding of the aetiology of alcohol misuse is already being fulfilled. Promises of new preventive and therapeutic interventions, if they also are to be fulfilled, require that a number of practical and ethical issues be addressed. Clinicians, researchers and others in the addictions field need to begin to address the ethical issues that are raised. PMID- 20575858 TI - NAALADase inhibition reduces alcohol consumption in the alcohol-preferring (P) line of rats. AB - N-acetyl-aspartyl-glutamate (NAAG) is a major peptide component of the brain, with millimolar tissue levels of 0.1-5 nmol/mg wet weight. NAAG is hydrolyzed by the enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase; glutamate carboxypeptidase II; EC no. 3.4.17.21) to N-acetyl-aspartate (NAA) and glutamate. Recently, a potent and selective NAALADase inhibitor termed 2 (phosphonomethyl)pentanedioic acid (2-PMPA) was identified that has a 300 pM Ki for NAALADase inhibition. Given the accumulating evidence indicating an important role of the glutamate system in alcoholism and dependence, the objective of this study was to evaluate the effects of systemic administration of 2-PMPA (50, 100 and 200 mg/kg; i.p.) upon the ethanol intakes of alcohol-preferring (P) rats. Female P rats (n = 8) received daily 1-hour scheduled access to a 10% (v/v) ethanol. In a within-subjects design, 2-PMPA treatments were tested once a week. Baseline ethanol drinking consisted of the mean of the 3 days prior to testing in which saline injections were given. Results indicated that, whereas the 200 mg/kg dose of 2-PMPA had no effect on ethanol intake, both the 50 and 100 mg/kg doses significantly reduced ethanol consumption by approximately 25% (p < 0.05) during the 1-hour access period. Body weights and 24-hour water intakes were not altered at any of the doses. These data suggest that the NAAG/NAALADase system may be involved in neuronal systems regulating alcohol-drinking behavior. PMID- 20575859 TI - The effects of acute cocaine administration in paradoxical sleep-deprived rats. AB - Recent studies demonstrate the action of cocaine on reward pathways, which are activated by pleasant stimuli. Cocaine's mechanism of action involves the blockade of dopamine and norepinephrine reuptake by the presynaptic terminal. Paradoxical sleep (PS) deprivation is known to induce several behavioural alterations most of which suggest the occurrence of supersensitivity of D2 and a subsensitivity of beta1and beta2receptors.The present study sought to examine the effects of PS deprivation on the actions of cocaine on the erection and ejaculation behaviours in rats. Four different doses of cocaine (3.5, 7.0, 15.0 and 30.0 mg/kg) were acutely administered to Wistar male rats, at the end of a 4 day period of PS deprivation or at the equivalent time-point to control animals. Moreover, 15 mg/kg of cocaine were administered in animals submitted to immobilization, footshock and forced swimming. The data were analysed by the Chi square test, and revealed that only PS-deprived animals exhibited penile erections and ejaculation behaviours, which were absent in control animals. PS deprivation increases the sexual behaviour of male rats, probably due to its action on dopaminergic systems. However, further studies need to be carried out in order to clarify the mechanisms involved between PS deprivation and cocaine. PMID- 20575860 TI - Experimental heart muscle damage in alcohol feeding is associated with increased amounts of reduced- and unreduced-acetaldehyde and malondialdehyde-acetaldehyde protein adducts. AB - Chronic and excessive alcohol consumption induces defined myocardial lesions characterized by impaired structural, mechanical and biochemical features. The pathogenic mechanisms are unknown, although it is possible that protein adduct formation by reactive metabolites of ethanol may be a contributory process. Hitherto, this has only been tested with respect to antibodies against reduced acetaldehyde protein adducts in clinical studies, despite the fact that during alcohol toxicity the formation of reduced-acetaldehyde, unreduced-acetaldehyde, malondialdehyde, malondialdehyde-acetaldehyde and hydroxyethyl protein adducts have been reported in non-cardiac tissues. It was our hypothesis that the heart is particularly sensitive to the formation of protein adducts in alcohol toxicity.To test this hypothesis, we analysed hearts from rats fed nutritionally complete liquid diets containing ethanol as 35% of total calories for 6 weeks, using the Lieber-DeCarli pair-feeding protocol. Control rats were treated identically and fed the same diet in which ethanol was replaced by isocaloric glucose. At the end of the feeding period, the hearts were dissected and ventricular muscle analysed. After 6 weeks' ethanol feeding, ELISA analysis showed increased amounts of reduced-acetaldehyde protein adducts (p < 0.01) unreduced-acetaldehyde (p < 0.01) and malondialdehyde-acetaldehyde (p= 0.01) protein adducts. However, malondialdehyde and alpha-hydroxyethyl-protein adducts were not significantly increased in hearts of ethanol-fed rats compared to pair fed control (p > 0.1 in both instances). This is the first report of acetaldehyde adduct formation in alcoholic cardiomyopathy. This suggests that either immune process may develop or functional impairment of affected proteins may occur. PMID- 20575861 TI - The dopamine D2 receptor (DRD2) gene-a genetic risk factor in heavy smoking? AB - Indications of a genetic predisposition to nicotine dependence have been derived from numerous epidemiological data and from individual genetic studies suggesting the involvement of the dopaminergic D2 receptor. Previous association studies defined the TaqlA polymorphism as a risk factor for addiction, in particular for alcoholism and tobacco dependence. Results of investigations into this polymorphism in 110 severely addicted smokers and a control group of 60 population-matched German non-smokers did not support these findings. However, our results indicate an association between the DRD2-Fokl-1 allele and the onset and intensity of smoking. PMID- 20575862 TI - Harman and norharman plasma levels in weaned alcoholics: correlations with depression and tobacco smoking. AB - Based on the hypothesis that beta-carbolines are involved in the pathogenesis of alcohol-related mood disturbance, harman and norharman levels were assayed in the blood plasma of alcoholics and correlated to the Hamilton Depression (HAM-D) scores after 3 and 5 weeks post-admission. Tobacco smoking was co-evaluated since it is known to influence beta-carboline levels. After a 3-week period, plasma harman but not norharman was increased in depressed alcoholics and positively related to the HAM-D sum-score (r = 0.47; p < 0.04) and to tobacco smoking (r = 0.56; p < 0.02). Since no correlation between depression and smoking was found, these data could account for the higher incidence of depressive symptoms in withdrawn alcoholics with increased harman levels. The partial correlations support this hypothesis. PMID- 20575863 TI - Changes in cigarette smoking among alcohol and drug misusers during inpatient detoxification. AB - Smoking prevalence and changes during inpatient detoxification were examined among 135 admissions to an inpatient alcohol and drug detoxification unit, of whom 83 (61.5%) were re-interviewed one week later. Ninety-two per cent of the initial sample were currently smokers; 87% of alcohol misusers, 97% of drug misusers and 100% of drug/alcohol misusers. Smokers consumed a daily mean of 27 cigarettes before admission. Those classified as heavy smokers (smoking 40 or more cigarettes prior to admission) decreased their smoking levels by an average of 10.5 cigarettes during detoxification. Light smokers (1-19 cigarettes per day) increased by a daily average of 8.6 cigarettes and intermediate smokers (20-39 cigarettes) by 4.9 cigarettes. The findings suggest a dose-dependent relationship between cigarette smoking and inpatient detoxification that requires further study. Over three-quarters of the sample expressed a desire to change their smoking behaviour, many of whom felt they would like help to tackle this change. Given the high smoking prevalence and reported interest in smoking cessation/reduction, there is an opportunity to address the smoking behaviour of drug and alcohol misusers entering inpatient care, whether during or after their detoxification. PMID- 20575864 TI - A compressed opiate detoxification regime with naltrexone maintenance: patient tolerance, risk assessment and abstinence rates. AB - Opiate detoxification using methadone programmes are inefficient and expensive. Rapid and ultra-rapid detoxification using precipitated withdrawal under heavy sedation or anaesthesia provide increased efficiency and speed, but are limited by the requirement for high-dependency facilities and are perceived as high-risk procedures. Procedures using precipitated withdrawal over longer periods with lower sedation are safer, but 20% of patients fail to tolerate these. Here we evaluate a naltrexone compressed opiate detoxification (NCOD) protocol. We investigated patient acceptance, organ function and abstinence rates on 504 consecutive patients undergoing treatment at the Harrogate Detox5 centre between February 1996 and January 1999. Ninety-eight per cent of patients completed the procedure; 81% of patients reported withdrawal was "better than expected". Only 3% of patients reported any pain. Laboratory investigations demonstrated no organ dysfunction. Abstinence rates post-detox were high with 71%, 61% and 51% of patients free of opiates 3, 6 and 12 months post-detox, respectively. Compliance with the naltrexone maintenance in abstinent patients was 66%, 68% and 30% at these time points. This NCOD protocol provides an efficient method of detoxifying opiate abusers with little patient discomfort or risk to health. Abstinence rates are better than those in comparable studies using other programmes. PMID- 20575865 TI - Chronic ethanol treatment and GABA(A) receptor alpha6 subunit gene expression: a study using alpha6 subunit-deficient mice. AB - Chronic alcohol administration increases the expression of cerebellum-specific GABA A receptor alpha6 subunit mRNA, protein and selective autoradiographical fingerprint on rat and mouse brain sections. We have tested whether the alpha6 gene is activated by chronic alcohol administration (daily p.o. injection of 2 g/kg during the first 3 days and 2.5 g/kg during the next 17 days) that produced tolerance in the rotarod test to motor impairment by acute challenge of ethanol (2 g/kg, i.p.). We utilized a mouse line engineered to express E. coli beta galactosidase enzyme and an unfunctional truncated alpha6 subunit under the control of the alpha6 gene promoter. Chronic ethanol treatment failed to alter the cerebellar beta-galactosidase activity when compared with no treatment and isocaloric sucrose treatment in groups of alpha6 subunit-deficient mice. The results suggest that tolerance to motor-impairing effects of ethanol can be achieved in the absence of alpha6 subunit-containing GABA(A) receptors, but that the reported upregulation of alpha6 gene transcription by ethanol treatment requires functional alpha6 subunits. PMID- 20575866 TI - Dopamine D4 receptor gene and severity of dependence. AB - Family, twin and adoption studies demonstrate that substance dependence is determined partially by genes. Recent studies in opiate-dependent subjects have found a significant excess of the long-long (LL) allele of the 48bp repeat in the coding sequence of the DRD4 gene. This study examined this association further in a sample of 60 opiate dependent, 51 alcohol-dependent and 64 normal, healthy control subjects. No significant association between the polymorphism at DRD4 and opiate or alcohol abuse was found. However, results yielded a significant main effect on severity of dependence, demonstrating that individuals with the LL allele rated their severity of dependence significantly higher than those who had the short-short (SS) allele :[F(2, 101) = 5.0, p < 0.01]. This study suggests that the DRD4 gene does not directly influence vulnerability to substance dependence, but that possession of the LL genotype significantly increases severity of dependence. PMID- 20575868 TI - A surgical safety checklist for Australia and New Zealand. PMID- 20575869 TI - Patient safety in medicine: are surgeons ready for checklists? PMID- 20575870 TI - Traditional undergraduate anatomy education--a contemporary taboo? PMID- 20575871 TI - Commentary on a procedure, a personal perspective: taking blood for haematological estimations. PMID- 20575872 TI - International medical graduate surgeons progress towards full specialist certification in Australia--barriers or facilitation? PMID- 20575873 TI - 25, 50 & 75 years ago. PMID- 20575874 TI - An academy of surgical educators: sustaining education--enhancing innovation and scholarship. AB - CONTEXT: The aims of surgical education, training and professional development programmes are to ensure surgeons will provide high quality health care throughout their professional lives. Development and delivery of these programmes requires a mixture of surgeons with a different but complimentary range of competencies in medical education, all eager to facilitate learning and support educational scholarship. METHODS: The Royal Australasian College of Surgeons has undertaken a major review of the challenges, risks and opportunities surrounding the development and delivery of its education and continuing professional development programmes. RESULTS: Conflicting demands on surgeons' time have compromised their availability for educational activities. At the same time, a decline has occurred in the recognition and value of teaching and educational scholarship as a consequence of financial rewards and prestige now coming principally from patient care and biomedical research. New educational methods have been introduced which have added to the complexities involved and the level of commitments required. In response, the College and its surgical specialty partners have established an Academy of Surgical Educators as a resource for the nine specialties of surgery. It will promote high quality patient care by providing expert educational leadership, guidance and advice and through the advancement and application of educational scholarship. CONCLUSION: The establishment of the Academy serves as a powerful symbol of the importance the College places on its core responsibility as an educational body. Working in association with the University Departments of Surgery throughout Australia and New Zealand, the Academy will better equip the College and its partner Specialist Societies and Associations to meet and sustain the increasingly sophisticated requirements involved in higher education. PMID- 20575875 TI - When can I drive doc? What vascular surgeons should know about fitness to drive. PMID- 20575876 TI - Radical prostatectomy: a systematic review of the impact of hospital and surgeon volume on patient outcome. AB - BACKGROUND: To assess the impact of hospital and surgeon volume on mortality, morbidity, length of hospital stay and costs of radical prostatectomy (RP). METHODS: This systematic review identified relevant studies published between 1997 and June 2007. Inclusion of papers was established through application of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. RESULTS: Compared with low volume hospitals, the included studies showed high volume hospitals demonstrated lower rates of mortality, postoperative complications and readmissions, and lower overall hospital costs. High volume surgeons similarly showed lower rates of postoperative complications and shorter length of stay compared with low volume surgeons, but no difference in mortality. CONCLUSIONS: From the literature obtained, patients undergoing RP performed by high volume providers may have better outcomes compared to low volume providers; however, any move to centralize RP must be further evaluated. PMID- 20575877 TI - Single-port laparoscopic right colonic resection. AB - BACKGROUND: The laparoscopic approach is a recognized treatment option for colonic resection. We present the first single-port operation for colonic resection using standard laparoscopic equipment and techniques. METHODS: A single port laparoscopic right colonic resection was successfully performed using GelPort (Applied Medical, Orange County, CA, USA) and a standard laparoscopic approach. RESULTS: The procedure was completed in 105 min through a single periumbilical incision. There was minimal blood loss and no post-operative problems. CONCLUSION: Single-port laparoscopic techniques can be applied to colonic surgery. It negates morbidity associated with trochar insertion and port sites. It should be performed by surgeons familiar with laparoscopic colorectal techniques. PMID- 20575878 TI - Review of the genetics of thyroid tumours: diagnostic and prognostic implications. AB - BACKGROUND: Thyroid nodules are common, but only a small proportion harbour malignancy. Despite this, the frequency of thyroid cancer is on the increase and thyroid malignancy is the most common endocrine malignancy. Preoperative diagnosis is based on ultrasound and radionucleotide imaging as well as the fine needle aspiration biopsy (FNAB). These biopsies yield a large proportion of indeterminate results due to inadequate material for cytological diagnosis, or due to the cytological similarity of FAs and follicular carcinomas. Recent advances in the understanding of the molecular pathogenesis of thyroid malignancy have led to the detection of characteristic genetic alterations in FNABs. This technology has the potential to increase the specificity of this test, combining cytological with genetic testing to reduce the number of indeterminate results, thereby reducing the number of thyroidectomies performed for benign disease. METHODS: This review examines the evidence for the presence of the common genetic alterations in thyroid cancer and outlines the pathological and clinical correlations of these mutations. The practicality and utility of measuring these genetic alterations in FNAB specimens is also outlined as well as the potential for these tests to alter primary management and follow-up of patients with nodular thyroid disease. CONCLUSION: It is likely that a combination of molecular testing and cytological examination of FNAB specimens will prove to be the most efficient and specific method of diagnosing thyroid cancer preoperatively. PMID- 20575879 TI - The safety and efficacy of ablative techniques adjacent to the hepatic vasculature and biliary system. AB - Ablative techniques may provide an alternative to resection in treating awkwardly placed hepatic malignancy adjacent to major vascular and biliary structures. The heat-sink effect may reduce efficacy adjacent to major vascular structures. Vascular occlusion improves efficacy but is associated with increased vascular and biliary complications. The safety and efficacy of ablation in these situations remain to be defined. Further studies comparing both safety and efficacy are needed. PMID- 20575880 TI - Can the outcome of open carpal tunnel release be predicted?: a review of the literature. AB - Carpal tunnel syndrome is a common condition affecting 1% of the population. Open carpal tunnel release is the most commonly performed procedure for this condition. About 70-90% of patients have good to excellent long-term outcomes with open carpal tunnel release. The remainder have poor outcomes. An understanding of factors which predict a poor outcome following open carpal tunnel release would be of benefit during preoperative counselling, and provides more accurate expectations of outcomes after surgery. We reviewed the published literature in the English language over the last 20 years in an attempt to ascertain predictors of poor outcomes following open carpal tunnel release. Patient factors such as age, sex and weight were not found to be predictors of a poor outcome following open carpal tunnel release. Similarly, physical examination had little usefulness, save for abductor pollicis wasting, for predicting post-surgical functional limitations, symptoms or satisfaction. Co morbid conditions such as diabetes, poor health status, thoracic outlet syndrome, double crush, alcohol and smoking have a worse prognosis. Normal nerve conduction studies preoperatively, direct nerve surgery such as neurolysis, abductor pollicis brevis muscle wasting and workers' compensation cases which involve lawyers preoperatively are all associated with worse outcomes. Postoperative physiotherapy may accelerate recovery but neither modifies functional recovery or reduces symptom occurrence. PMID- 20575881 TI - Emergency laparoscopic splenectomy for haemoperitoneum because of ruptured primary splenic pregnancy: a case report and review of literature. AB - BACKGROUND: Primary abdominal pregnancies are potentially life-threatening, particularly without an accurate preoperative diagnosis. CASE: A 41-year-old woman presented to the emergency room with 2 days-lasting left upper quadrant abdominal pain, irradiated to the left shoulder. An urine beta-human chorionic gonadotropin test was positive. Transvaginal sonography raised a suspicion of ectopic pregnancy. The patient was then submitted to abdominal laparoscopy that revealed no sign of active bleeding or ectopic pregnancy. Because of worsening of abdominal pain and progressive anaemia, the patient underwent abdominal ultrasound and multislice computerized tomography scan (TC) that showed the presence of a mass at the superior splenic pole with haemoperitoneum. The patient was taken to the operating room and submitted to a laparoscopic total splenectomy. The post-operative course was uneventful, and the patient was discharged 8 days after intervention. CONCLUSION: Abdominal pregnancy should be considered in the differential diagnosis of acute abdomen in women of reproductive age. Abdominal ultrasound and computerized tomography studies must be performed before operative treatment if an ectopic pregnancy is suspected and no intrauterine gestational sac could be showed on transvaginal sonography. PMID- 20575882 TI - Infected pancreatic necrosis: minimizing the cut. AB - The challenge for the pancreatologist managing patients with infected pancreatic necrosis is to devise a treatment algorithm that enables recovery but at the same time limits the morbidity and mortality. The current gold standard remains open necrosectomy. Recent literature contains scattered reports of endoscopic, radiologic, laparoscopic, percutaneous and lumbotomy approaches to managing patients with this condition. This literature review addresses the role of techniques that aim to minimize the physiological insult to the patient with infected pancreatic necrosis. PMID- 20575883 TI - Seat belt injury to the female breast: review and discussion of its surgical management. AB - With the use of the three-point lap-diagonal seat belt restraint, there has been a reduction in the number of deaths caused by automobile trauma. However, a new pattern of injury has emerged, the 'seat-belt syndrome', which comprises a constellation of injuries including soft tissue injury to the breast. Given that seat belt legislation is becoming more widespread, it is likely that the incidence and reporting of these injuries will become more common. In this paper, we provide an overview of the varied clinical and radiological presentations, and suggested management of seat belt injury to the female breast. The consequences of such injury can be severe in their functional, psychosocial and aesthetic impact, and thus, using an index case as an example, the previously unreported area of breast reconstruction in a breast deformed as a result of blunt trauma is discussed, highlighting some of its challenges. PMID- 20575885 TI - Review of imaging of scaphoid fractures. AB - Scaphoid fractures are the most common fractures of the carpus, accounting for 79% of all carpal fractures. Early diagnosis of scaphoid fractures is imperative owing to potential complications following the fracture, including non-union, avascular necrosis, carpal instability and osteoarthritis. Plain radiography remains the initial imaging modality to assess scaphoid fractures. Magnetic resonance imaging (MRI) is excellent in the detection of clinically suspected, but initially radiographically negative, scaphoid fractures. Cost-effectiveness analysis studies have demonstrated MRI is effective in this setting. Gadolinium enhanced MRI has been shown to be superior to unenhanced MRI in the detection of avascular necrosis. Computerized tomography scan is the preferred modality to assess the intricacies of scaphoid fracture, including fracture location and deformity, as well as union status. This review paper explores the recent advances in imaging of the scaphoid, with reference also to avascular necrosis and non-union following a scaphoid fracture. PMID- 20575884 TI - Management of bile duct injury after laparoscopic cholecystectomy: a review. AB - BACKGROUND: Bile duct injury following cholecystectomy is an iatrogenic catastrophe which is associated with significant perioperative morbidity and mortality, reduced long-term survival and quality of life, and high rates of subsequent litigation. The aim of this article was to review the management of bile duct injury after cholecystectomy. METHODS: Medline and PubMed database search was undertaken to identify articles in English from 1970 to 2008 using the key words 'bile duct injury', 'cholecystectomy' and 'classification'. Additional papers were identified by a manual search of the references from the key articles. Case report was excluded. RESULTS: Early recognition of bile duct injury is of paramount importance. Only 25%-32.4% of injuries are recognized during operation. The majority of patients present initially with non-specific symptoms. Management depends on the timing of recognition, the type, extent and level of the injury. Immediate recognition and repair are associated with improved outcome, and the minimum standard of care after recognition of bile duct injury is immediate referral to a surgeon experienced in bile duct injury repair. There is a growing body of literature supporting the importance of early referral to a tertiary care hospital which can provide a multidisciplinary approach to treat bile duct injury. Inadequate management may lead to severe complications. CONCLUSIONS: None of the classification system is universally accepted as each has its own limitation. The optimal management depends on the timing of recognition of injury, the extent of bile duct injury, the patient's condition and the availability of experienced hepatobiliary surgeons. PMID- 20575886 TI - Intramural oesophageal dissection. AB - Intramural oesophageal dissection is an uncommon but important clinical condition. It often occurs in patients who are anticoagulated, and the clinical presentation may include chest pain, dysphagia and haematemesis. The aim of this review was to determine an appropriate treatment algorithm for patients with suspected intramural oesophageal dissection. We conducted a literature review using PubMed and MedLine up until December 2008. We also reported on our own case series of three patients with intramural oesophageal dissection presenting at two Adelaide hospitals over the past 5 years. Recognition of the risk factors and clinical symptoms associated with this condition is imperative to avoid unnecessary and potentially harmful investigations and therapy. Intramural oesophageal dissection usually follows a benign course requiring conservative therapy only. PMID- 20575887 TI - Nonsteroidal anti-inflammatory drugs-associated colopathy. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used worldwide, and their complications in the upper gastrointestinal tract are well described in the literature and well known to clinicians. However, complications in the large bowel are being increasingly recognized and reported. This review aims to address the different aspects of NSAIDs-associated colopathy. METHODS: This is a review article addressing NSAIDs colopathy. A Medline-based search was performed for articles published between 1950 and 2008 on this condition. Keywords detailed were colonic disease, ulcers, strictures and/or diaphragm strictures. Only articles in the English language were considered. RESULTS: The articles identified included letters to the editors, case reports, case series, review articles and few original research papers. The review was structured in a narrative style in different sections addressing pathophysiology, clinical presentation and management. CONCLUSIONS: NSAIDs colopathy is a rare benign condition. Current evidence only suggests an association with prolonged use of the NSAIDs, however, there are no studies to support the direct causation. The presentation is non-specific, and the commonest findings on endoscopy are ulceration and diaphragm-like strictures. The importance of identifying this condition is to prevent complications and also to be able to differentiate it from other conditions such as inflammatory bowel disease (IBD) and malignancy. PMID- 20575888 TI - Merkel cell carcinoma metastatic to the stomach. PMID- 20575889 TI - Salmonella enteritidis-infected intra-abdominal lymphangioma. PMID- 20575890 TI - Calcified giant intracranial aneurysms. PMID- 20575897 TI - Thromboprophylaxis. PMID- 20575896 TI - Chronic pain following a Lichtenstein inguinal hernia repair: a clinical and legal dilemma (ANZ J. Surg. 2009; 79: 517-20). PMID- 20575898 TI - Re: Surgical harassment. PMID- 20575899 TI - Use of ultrasonic shears in thyroidectomy--a note of caution. PMID- 20575900 TI - Skin grafts a rural general surgical perspective (ANZ J. Surg. 2009; 79: 362-8). PMID- 20575901 TI - Decompressive surgery for large territory anterior circulation cerebral infarction: the earlier, the better? PMID- 20575902 TI - Gall bladder cancer and Mirizzi syndrome: alternative explanation to the common belief. PMID- 20575903 TI - Left paraduodenal hernia diagnosed preoperatively. PMID- 20575904 TI - Toxic nodular goiter with thyroid papillary microcarcinoma. PMID- 20575906 TI - Traumatology in Australia: provision of clinical care and trauma system development. PMID- 20575907 TI - The use of statistics in the ANZ Journal of Surgery. PMID- 20575908 TI - Seeking optimal trauma care in Victoria. PMID- 20575909 TI - Endoscopic surveillance in colitis in 2010: time for a change? PMID- 20575910 TI - The role of prophylactic antibiotics in thoracostomy. PMID- 20575911 TI - Keratoacanthoma: is it really a variant of squamous cell carcinoma? PMID- 20575912 TI - 25, 50 & 75 years ago. PMID- 20575913 TI - Surgical history of ancient China: Part 2. AB - In this second part of ancient Chinese surgical history, the practice of bone setting in China began around 3000 years ago. Throughout this period, significant progress was made, some highlights of which are cited. These methods, comparable with Western orthopaedic technique, are still being practised today. In conclusion, the possible reasons for the lack of advancement in operative surgery are discussed, within context of the cultural, social and religious background of ancient China. PMID- 20575914 TI - Making sense of emergency surgery in New South Wales: a position statement. AB - BACKGROUND: Emergency surgery is a major component of the provision of surgical services and makes up a substantial volume of the workload of surgeons in many hospitals. It is often more complex and surgically challenging than elective surgery. However, little attention has been concentrated on the management or resource requirements of emergency surgery. METHOD: This article identifies principles for models of emergency surgery care and describes how they can be incorporated into a redesign of emergency surgery. They have been developed and are endorsed by experienced surgical staff routinely coping with the challenges of emergency surgery. RESULTS: The benefits of redesigning emergency surgery will be realized by an active partnership between managers, surgeons and surgical teams. The anticipated clinical benefits include improved patient outcomes, enhanced patient and surgical team satisfaction, and increased trainee supervision in emergency surgery. Significant management benefits will ensue from high rates of emergency operating theatre utilization, reduced patient cancellations and reduction in after-hours costs. This unplanned but predictable workload will be managed in a planned and predictable fashion. CONCLUSION: Reform of emergency surgery services is a necessity and not a choice. The development of the emergency surgery guidelines for New South Wales is a step in the right direction. The principles identified in the guidelines should be adapted and implemented across Australia if sustainable, safe and efficient emergency surgery services are to be provided. Patients will expect nothing less. PMID- 20575916 TI - Clinical practice guidelines for the management of acute limb compartment syndrome following trauma. AB - BACKGROUND: Acute compartment syndrome is a serious and not uncommon complication of limb trauma. The condition is a surgical emergency, and is associated with significant morbidity if not managed appropriately. There is variation in management of acute limb compartment syndrome in Australia. METHODS: Clinical practice guidelines for the management of acute limb compartment syndrome following trauma were developed in accordance with Australian National Health and Medical Research Council recommendations. The guidelines were based on critically appraised literature evidence and the consensus opinion of a multidisciplinary team involved in trauma management who met in a nominal panel process. RESULTS: Recommendations were developed for key decision nodes in the patient care pathway, including methods of diagnosis in alert and unconscious patients, appropriate assessment of compartment pressure, timing and technique of fasciotomy, fasciotomy wound management, and prevention of compartment syndrome in patients with limb injuries. The recommendations were largely consensus based in the absence of well-designed clinical trial evidence. CONCLUSIONS: Clinical practice guidelines for the management of acute limb compartment syndrome following trauma have been developed that will support consistency in management and optimize patient health outcomes. PMID- 20575915 TI - A comparison of severely injured trauma patients admitted to level 1 trauma centres in Queensland and Germany. AB - BACKGROUND: The allocation of a trauma network in Queensland is still in the developmental phase. In a search for indicators to improve trauma care both locally as state-wide, a study was carried out comparing trauma patients in Queensland to trauma patients in Germany, a country with 82.4 million inhabitants and a well-established trauma system. METHODS: Trauma patients > or =15 years of age, with an Injury Severity Score (ISS) > or = 16 admitted to the Princess Alexandra Hospital (PAH) and to the 59 German hospitals participating in the Trauma Registry of the German Society for Trauma Surgery (DGU-G) during the year 2005 were retrospectively identified and analysed. RESULTS: Both cohorts are comparable when it comes to demographics and injury mechanism, but differ significantly in other important aspects. Striking is the low number of primary admitted patients in the PAH cohort: 58% versus 83% in the DGU-G cohort. PAH patients were less physiologically deranged and less severely injured: ISS 25.2 +/- 9.9 versus 29.9 +/- 13.1 (P < 0.001). Subsequently, they less often needed surgery (61% versus 79%), ICU admission (49% versus 92%) and had a lower mortality: 9.8% versus 17.9% of the DGU-G cohort. CONCLUSIONS: Relevant differences were the low number of primary admissions, the lesser severity of injuries, and the low mortality of the patients treated at the PAH. These differences are likely to be interrelated and Queensland's size and suboptimal organization of trauma care may have played an important role. PMID- 20575917 TI - Management of spleen injuries: the current profile. AB - BACKGROUND: There has been a shift from operative to conservative management of splenic injuries in the last two decades, but the current practice in Australia is not known. This study aims to determine the profile of splenic injury in major trauma victims and the approach to treatment in Victoria for the last 2 years. METHODS: A review of prospectively collected data from the Victorian State Trauma Registry (VSTR) from July 2005 to June 2007 was conducted. Demographic data, details of the event, clinical observations, management and associated outcomes were extracted from the database. The patients were categorized into four groups according to management (conservative, splenectomy, embolization and repair) and were compared accordingly. Multivariate binary logistic regression was performed to identify predictors of treatment (conservative versus splenectomy) on arrival. RESULTS: Of the 318 major trauma patients with splenic injuries, 186 (59%) were treated conservatively, 103 (32%) with splenectomy, 17 (5%) with arterial embolization and 12 (4%) with repair. Of these, 14 (14%) splenectomy cases and 2 (12%) embolization cases did not receive their respective treatments within 24 h. The severity of the spleen injury (as measured by the Abbreviated Injury Scale (AIS)) and age were identified as significant independent predictors of the form of treatment provided. CONCLUSION: In Victoria, conservative management is the preferred approach in patients with minor (AIS = 2) to moderate (AIS = 3) splenic injuries. The low rates of embolization warrant further research into whether splenectomy is overused. PMID- 20575918 TI - Prospective randomized comparison of endobutton versus cross-pin femoral fixation in hamstring anterior cruciate ligament reconstruction with 2-year follow-up. AB - BACKGROUND: To determine if there is a different clinical outcome after TransFix versus endobutton femoral fixation in hamstring anterior cruciate ligament (ACL) reconstruction. METHODS: Twenty-nine patients were randomized into either Endobutton (Smith & Nephew, Andover, MA, USA) (n= 13) or TransFix (Arthrex, Naples, FL, USA) (n= 16) femoral fixation in hamstring ACL reconstruction. The distal fixation was with a bioabsorbable interference screw. The evaluation methods were clinical history and examination, KT1000 arthrometry for laxity as well as the International Knee Documentation Committee (IKDC) scores over a 2 year time frame. RESULTS: There were no significant differences between the study groups preoperatively. For the 2-year follow-up, 11 patients in the Endobutton group and 13 patients in the TransFix group were available (greater than 80%). No statistical differences between the two groups were found at the 1- or 2-year follow-up examinations. At the 2-year follow-up, 72.7% of the Endobutton and 84.6% of the TransFix group patients were in the IKDC A or B categories. Additional procedures postoperatively occurred more frequently in the TransFix group. CONCLUSIONS: There were no significant differences in the results for either technique of femoral fixation. PMID- 20575919 TI - Diagnosis of blunt traumatic ruptured diaphragm: is it still a difficult problem? AB - BACKGROUND: Blunt traumatic rupture of the diaphragm (BTRD) is uncommon. The diagnosis can be easily overlooked, and radiological findings misinterpreted. In a 15-year experience at the two major trauma hospitals in Brisbane reported in 1991, 85 patients with BTRD were treated, and the diagnosis not always made expeditiously. With the introduction of mandatory Early Management of Severe Trauma course training in the 90s and newer diagnostic tools, it might be expected that BTRD would be a less problematic diagnosis. The aim of this study was to review the incidence, diagnosis and outcome of BTRD at Auckland City Hospital over the last 10 years. METHODS: Retrospective review of Auckland City hospital trauma registry between 1996 and 2005. Demographics include age, gender, injury severity score (ISS), length of stay, ICU admission days, methods of diagnosis and patient outcomes were reviewed. RESULTS: Twenty-eight patients had TRD as result of blunt injury. Median ISS was 28.5. Most of the patients were diagnosed at the time of laparotomy for other associated injuries. Road traffic crash was the most common cause. Twenty-one out of 28 patients were discharged alive. CONCLUSION: Diagnosis of BTRD remains difficult. It is rarely isolated. It requires a high index of suspicion. If suspected, chest X-ray (CXR) and other more advanced imaging modalities can be used as confirmatory tools. PMID- 20575920 TI - Use of face masks by non-scrubbed operating room staff: a randomized controlled trial. AB - BACKGROUND: Ambiguity remains about the effectiveness of wearing surgical face masks. The purpose of this study was to assess the impact on surgical site infections (SSIs) when non-scrubbed operating room staff did not wear surgical face masks. METHODS: Eight hundred twenty-seven participants undergoing elective or emergency obstetric, gynecological, general, orthopaedic, breast or urological surgery in an Australian tertiary hospital were enrolled. Complete follow-up data were available for 811 patients (98.1%). Operating room lists were randomly allocated to a 'Mask group' (all non-scrubbed staff wore a mask) or 'No Mask group' (none of the non-scrubbed staff wore masks). The primary end point, SSI was identified using in-patient surveillance; post discharge follow-up and chart reviews. The patient was followed for up to six weeks. RESULTS: Overall, 83 (10.2%) surgical site infections were recorded; 46/401 (11.5%) in the Masked group and 37/410 (9.0%) in the No Mask group; odds ratio (OR) 0.77 (95% confidence interval (CI) 0.49 to 1.21), p = 0.151. Independent risk factors for surgical site infection included: any pre-operative stay (adjusted odds ratio [aOR], 0.43 (95% CI, 0.20; 0.95), high BMI aOR, 0.38 (95% CI, 0.17; 0.87), and any previous surgical site infection aOR, 0.40 (95% CI, 0.17; 0.89). CONCLUSION: Surgical site infection rates did not increase when non-scrubbed operating room personnel did not wear a face mask. PMID- 20575921 TI - Comparison of open and closed staff-assisted glove donning on the nature of surgical glove cuff contamination. AB - BACKGROUND: We have observed that surgical glove cuffs commonly fold over during an operation, exposing the inside of the glove cuff to the sterile field and wound, a potential source of contamination if the inside of the glove cuff has been in contact with the fingers during glove donning. We hypothesize that open staff-assisted gloving results in more inside-glove cuff contamination than a closed staff-assisted technique. METHOD: We performed a blinded, randomized study comparing open and closed staff-assisted glove donning. Two surgeons were gloved 20 times after covering their fingers and hands with GlitterBug powder. The gloves were turned inside out and the distance of GlitterBug powder from the free edge of the cuff was measured. RESULTS: Staff-assisted open glove donning was associated with significantly more glove cuff contamination than closed staff assisted glove donning (P= 0.001). CONCLUSION: Given glove cuff 'turn down' intra operatively, we strongly recommend closed staff-assisted gloving. PMID- 20575922 TI - Enterocutaneous fistula: a single-centre experience. AB - BACKGROUND: Enterocutaneous fistulae (ECFs) present a difficult management problem and can cause significant morbidity. The aim of the study was to assess the outcome of these patients. METHODS: A retrospective chart review of all patients with ECF managed at a tertiary centre between 1996 and 2006 was performed. Demographic, management and outcome data including ECF closure, morbidity and mortality were recorded. RESULTS: A total of 33 patients (17 male) were identified with ECF (median age: 63 years, range: 27-84). The primary aetiology was Crohn's (30%), anastomotic leak (24%), iatrogenic (18%), mesh (6%), neoplasia (6%) and other (16%). Definitive surgery was undertaken in 21 (64%) at a median of 6.4 months (0.4-72 range) following presentation. Twenty percent of patients required emergency surgical intervention and 5 patients required preoperative total parenteral nutrition (TPN). Surgical management was formal resection and reanastomosis in all patients, with a mean operative time of 4.75 h (standard deviation = 1.8). The median hospital stay for the operative group was 19 days (7-85). Four patients required post-operative TPN with one patient requiring home TPN. Fistula closure rate was 97% (operative group: 21 out of 21; non-operative group: 11 out of 12). Mean follow-up was 37.3 months (0.5-217). Six (19%) operative patients developed fistula recurrence. There were two deaths at 2 and 5 months (fistula aetiology malignant colonic fistula and radiation enteritis, respectively). CONCLUSION: Patients with ECF can be treated with low morbidity and low recurrence rate in a multidisciplinary setting. We believe that patients with ECF should be referred to specialist units for management. PMID- 20575924 TI - Benign multicystic mesothelioma. PMID- 20575923 TI - Gyrus PlasmaKinetic bipolar coagulation device for liver resection. AB - BACKGROUND: Liver parenchymal transection can be associated with significant blood loss and morbidity. We present our initial experience with the Gyrus PlasmaKinetic coagulation device in liver parenchymal resection in both cirrhotic and non-cirrhotic patients. METHODS: Liver resections were performed in 51 consecutive patients, from 20 July 2005 to 31 August 2007, using the Gyrus PlasmaKinetic coagulator. Requirement for blood transfusions, operating time, duration of hospital stay and major complications were evaluated initially for the group as a whole. Subsequently, the 11 patients with histologically confirmed cirrhosis (nine men, two women, median age 54 years, range 24-74 years) were compared with 40 patients without cirrhosis (25 men, 15 women, median age 57 years, range 24-87 years). RESULTS: There were 34 men and 17 women. The median age was 56 (range 24-87 years). There were 48 open procedures and 3 laparoscopic procedures. There were 30 major resections (>2 segments) and 21 minor resections (one to two segments). The overall median operating time was 260 min (range 90 690). Length of stay had a median of 9 days, range 4-50 days. Twenty-one patients (41%) required a blood transfusion. Two biliary leaks were observed in non cirrhotic patients initially before the settings of the Gyrus device were optimized. CONCLUSIONS: The Gyrus PlasmaKinetic coagulation device is a novel instrument for hepatic parenchymal transection in liver resection, which can be safely used in cirrhotic and non-cirrhotic patients. PMID- 20575925 TI - Osteoid osteoma of the proximal phalanx of the finger. PMID- 20575926 TI - A case of massive gastrointestinal haemorrhage: an important consideration in travellers. PMID- 20575931 TI - An unrecognized contributor towards the introduction of surgical skills training. PMID- 20575932 TI - Reducing the length of stay for patients undergoing colorectal surgery. PMID- 20575933 TI - Hepatic portal venous gas. PMID- 20575934 TI - Congenital unilateral absence of the vas deferens. PMID- 20575935 TI - Splenosis and accessory spleens. PMID- 20575936 TI - A useful instrument for parotidectomy. PMID- 20575937 TI - Hiatal hernia detected by iodine-131 scan for ablation of thyroid carcinoma. PMID- 20575938 TI - Mesenteric panniculitis: a diagnosis of exclusion. PMID- 20575939 TI - An update on pseudoaneurysm of superficial temporal artery. PMID- 20575940 TI - Idiopathic granulomatous appendicitis: a report of three consecutive cases. PMID- 20575941 TI - Tumour banking as part of routine clinical practice. PMID- 20575942 TI - Paradigm shifts in the management of faecal incontinence. PMID- 20575943 TI - Ethical dilemma for surgical educators. PMID- 20575945 TI - Review of anatomy education in Australian and New Zealand medical schools. AB - Anatomy instruction at Australian and New Zealand medical schools has been the subject of considerable debate recently. Many commentators have lamented the gradual devaluation of anatomy as core knowledge in medical courses. To date, much of this debate has been speculative or anecdotal and lacking reliable supporting data. To provide a basis for better understanding and more informed discussion, this study analyses how anatomy is currently taught and assessed in Australian and New Zealand medical schools. A mailed questionnaire survey was sent to each of the 19 Australian and 2 New Zealand medical schools, examining the time allocation, content, delivery and assessment of anatomy for the 2008 academic year. Nineteen of the 21 (90.5%) universities invited to participate completed the survey. There was considerable variability in the time allocation, content, delivery and assessment of anatomy in Australasian medical schools. The average total hours of anatomy teaching for all courses was 171 h (SD +/- 116.7, range 56/560). Historical data indicate a major decline in anatomy teaching hours within medical courses in Australia and New Zealand. Our results reveal that as there is no national curriculum for anatomy instruction, the curriculum content, instruction methodology and assessment is highly variable between individual institutions. Such variability in anatomy teaching and assessment raises an important question: is there also variable depth of understanding of anatomy between graduates of different medical courses? PMID- 20575946 TI - Audit of the utilization of time in an orthopaedic trauma theatre. AB - BACKGROUND: The efficient use of operating theatres is important to ensure optimum cost-benefit for the hospital and to clear waiting lists. This audit uses the orthopaedic trauma theatre as a model to assess the theatre efficiency at our institution. METHODS: We performed a retrospective audit using data gathered from the operating theatre database at our institution. We considered each component of the operating theatre process and integrated them to give a combined value for surgical and anaesthetic time (end utilization) and total theatre efficiency (operating theatre utilization). RESULTS: Results showed that relative to the standards set, changeover time and start times were sub-standard, with consistently prolonged changeovers and late starts. End utilization and operating theatre utilization were 78.8 and 81%, against a standard of 77 and 85-90%, respectively. However, these figures may be misleading due to sub-standard performance in changeover time and other variables. CONCLUSIONS: We have highlighted inefficiency in the orthopaedic trauma theatre at our institution and suggest various strategies to improve this that may be applied universally. PMID- 20575947 TI - The need for patellar resurfacing in total knee arthroplasty: a literature review. AB - The controversy over whether or not to routinely resurface the patella during a total knee arthroplasty has persisted despite three decades of successful joint replacement procedures. Advocates for routine patellar resurfacing admit the occasional need for secondary patellar resurfacing and declare increased incidence of anterior knee pain in patients with non-resurfaced patellae as a cause for worry. Surgeons that leave the patella unresurfaced cite avoidance of complications that include patellar fracture, avascular necrosis, patellar tendon injury and instability. This review discusses the available literature on patellar resurfacing through an evidence-based analysis of randomized and pseudo randomized controlled trials and published meta-analyses to date. The published literature seems to favour resurfacing the patellar routinely. Selective patellar resurfacing would be the ideal solution if sound pre-operative criteria could be established. So far, a method for accurately predicting which patients can avoid patellar resurfacing has not been found. Future research looking at patellar resurfacing should concentrate on developing criteria for selecting those patients that would benefit from patellar resurfacing and those that would do as well without resurfacing, and thus, limiting potential surgical complications. PMID- 20575948 TI - Centralization and the relationship between volume and outcome in knee arthroplasty procedures. AB - BACKGROUND: Centralization aims to reduce adverse patient outcomes by concentrating complex surgical procedures in specified hospitals. OBJECTIVES: This review assessed the efficacy of centralization for knee arthroplasty by examining the relationship between hospital and surgeon volume and patient outcomes. DATA SOURCES AND REVIEW METHODS: The systematic review identified studies using multiple databases, including Medline and Embase. Two independent researchers ensured studies met the inclusion criteria. Morbidity, mortality, length of stay, financial outcomes and statistical rigour were examined. Correlations between volume and outcome were reported. RESULTS: Twelve primary knee arthroplasty studies examined hospital volume, which was significantly associated with decreased morbidity (five of seven studies), mortality (two of five studies) and length of stay (two of three studies). Three primary knee arthroplasty studies examined surgeon volume, which was significantly associated with decreased morbidity (two of three studies), mortality (zero of two studies) and length of stay (one of one study). Two revision knee arthroplasty studies examined hospital volume. One study examined but did not test for significance between hospital volume and patient morbidity; both studies examined volume and patient mortality reporting inconclusive results; and one study reported no significant association between volume and length of stay. None of the revision knee arthroplasty studies examined surgeon volume. CONCLUSIONS: Significant associations between increased hospital and surgeon volume and improved patient outcomes were reported. However, when these results were separated by arthroplasty type, the association appeared tenuous. Judgements regarding centralization of knee arthroplasty should be made with caution until further evidence is published. PMID- 20575949 TI - Roentgen stereophotogrammetric analysis and clinical assessment of unipolar versus bipolar hemiarthroplasty for subcapital femur fracture: a randomized prospective study. AB - BACKGROUND: Hemiarthroplasty is a well-established treatment for displaced subcapital fracture, but controversy exists about the optimal implant type. Bipolar hemiarthroplasty has proposed advantages over unipolar hemiarthroplasty in terms of better clinical results and decreased wear of acetabular cartilage. METHODS: This study is a randomized prospective study of 51 patients (52 hips) receiving either bipolar or unipolar hemiarthroplasty for displaced subcapital fractures. The outcome measurements were clinical scores and Roentgen stereophotogrammetric analysis (RSA) analysis to determine the rate of acetabular wear. RESULTS: Twenty-three patients completed 2-year follow-up. The RSA data demonstrated that there was slightly less acetabular wear by bipolar prostheses than by unipolar. The combined mean three-dimensional wear of the bipolar prostheses was 0.6 mm compared with 1.5 mm for the unipolar prostheses (P= 0.04). The bipolar group generally achieved higher scores in terms of the Harris Hip Score, Western Ontario and McMaster University Index of Osteoarthritis (WOMAC) questionnaire and 6-min walk test. These results were statistically significant at 3 months but not at 12 and 24 months. CONCLUSION: This study suggests that while the bipolar prosthesis performs slightly better than the unipolar in terms of acetabular cartilage wear and clinical outcomes, it remains debatable whether the benefits are worth the increased cost of the prosthesis. PMID- 20575950 TI - Therapeutic embolization in the treatment of recurrent haemarthrosis following knee arthroplasty. AB - Recurrent spontaneous haemarthrosis after knee arthroplasty occurs in less than 1% of cases, commonly thought to be the result of impingement of hypertrophic vascular synovium or fat pads, and exacerbated by anti-coagulation or anti platelet therapy. Traditional treatment comprises an initial period of rest followed by open or arthroscopic washout, and by synovectomy if bleeding recurs or fails to settle. We present three cases of recurrent haemarthrosis following knee arthroplasty, which were successfully treated by angiography and feeding vessel coil embolization. An injury to one of the genicular arteries was identified as the cause of bleeding in all three cases; one manifest as a traumatic arteriovenous fistula. Bleeding ceased in all cases without recurrence (follow-up period 6 months-5 years, median of 2 years). Endovascular treatment offers a minimally invasive treatment option in selected cases of recurrent post operative haemarthrosis. PMID- 20575951 TI - Study of botulinum toxin A in neurogenic bladder due to spina bifida in children. AB - BACKGROUND: We report results of a pilot study investigating the safety and efficacy of Botulinum A toxin on urinary incontinence and bladder function in children with neurogenic bladder. METHODS: This was a prospective, non-randomized clinical trial. Seven children with median age of 16 years with spina bifida who had high storage pressures, poor bladder compliance and had failed treatment with anticholinergic medications were offered a single intra-detrusor injection of Botulinum A toxin. All subjects were on clean intermittent catheterization before and during the study. Follow-up videourodynamic studies were performed at 1 month, between 3 and 6 months, and at 9 months. Data were collected on safety and on subjective outcomes through validated questionnaires filled out by patients at each visit. RESULTS: In majority of the patients (5/7), the injection produced an increase in bladder compliance (P < 0.05) and an improvement in incontinence (P < 0.05) at 1-month follow-up. However, in two patients whose baseline bladder capacity was markedly reduced (<200 mL), the improvement was very minimal. The beneficial effects in bladder compliance and incontinence dissipated by 9 months. The changes in subjective outcomes (incontinence and satisfaction scores) did not parallel the changes in urodynamics through the study period. No side effects of Botulinum toxin were seen. CONCLUSION: Botulinum A toxin injection produces beneficial urodynamics and clinical effects. These beneficial effects last for approximately 9 months. There is a poor correlation between improvement in the urodynamics and the subjective outcomes. Botulinum A toxin injection is a safe alternative treatment for patients with spina bifida and a neurogenic bladder. PMID- 20575952 TI - Nasopharyngeal carcinoma: differences in presentation between different ethnicities in the New Zealand setting. AB - INTRODUCTION: There is an elevated incidence of nasopharyngeal carcinoma (NPC) in the Maori and Pacific Island (MPI) population as well as the Asian population in New Zealand; however, no studies have been conducted to evaluate how the two populations differ in their clinical presentation according to the TNM stage. METHODS: A retrospective review was conducted of all patients presenting to the Auckland City Hospital ENT department with a newly diagnosed NPC between the years 1995 and 2007 inclusive. The patient's radiological and biopsy results were reviewed, and each patient was staged according to the TNM stage at presentation as per the revised 2002 American Joint Committee on Cancer staging criteria. The Fisher's exact test was used to compare the differences between ethnicities in the T and N stages of the disease at presentation; the Cochran-Armitage Trend test was used to look for statistically significant trends. RESULTS: There was a statistically significant difference in T stage at presentation between MPIs and Asians (P < 0.0001), with a positive, statistically significant (P < 0.0001) trend indicating that MPIs present with greater T stage. A statistically significant difference in the N stage at diagnosis between MPIs and Asians, independent of the T stage, was found at stages T2 (P = 0.046) and T4 (P = 0.0083), with a statistically significant trend (T2 -P = 0.009; T4 -P = 0.026). CONCLUSIONS: These results show that MPIs have a more advanced local NPC disease than Asians at presentation, and that for specific T stages, the nodal disease is also more advanced than that found in Asians. PMID- 20575953 TI - Risk factors of mortality in non-trauma exsanguinating patients that require damage control laparotomy. AB - BACKGROUND: Since introduction of damage control (DC) approach to non-trauma setting is relatively late, the risk factors associated with this procedure remain undefined. This study was aimed at identifying factors responsible for the mortality. METHODS: Over a 5-year period (from February 2002 to February 2007), consecutive non-trauma patients who required DC laparotomy (DCL) with gauze packing for control of indomitable abdominal haemorrhage in our institute were included. Clinical, laboratorial and operative factors influencing in-hospital or 30-day mortality were analysed. RESULTS: A total of 26 patients underwent DCL with packing in an attempt to control severe abdominal haemorrhage. There were seven (26.9%) deaths in hospital or within 30 days of DCL. Increase in age, higher initial physiological score and operative severity score assessed by the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity scoring system, lower initial body temperature, lower initial platelet (PLT) counts, greater intra-operative blood loss, presence of perioperative multiple organ dysfunction syndrome were all associated with increased risk of mortality on univariate analysis (P < 0.05). On multivariate analysis, only decrease in PLT counts (P = 0.042, OR = 0.969, 95% CI = 0.940-0.999) and increase in age (P = 0.035, OR = 1.152, 95% CI = 1.010-1.313) were significant independent factors affecting mortality. CONCLUSIONS: Decrease in PLT counts and increase in age are the independent risk factors related to death in non-trauma series that require DCL with packing. DCL should be performed early as for patients with these risk factors. PMID- 20575954 TI - Protective role of coenzyme Q10 in two models of rat lung injury. AB - BACKGROUND: Ischaemia-reperfusion injury is a life-threatening complication of lung transplantation. Attempts to ameliorate this injury have included optimization of donor management and improving techniques of lung preservation. However, few investigators have sought to pretreat potential recipients. Coenzyme Q(10) (CoQ(10)) is a potent antioxidant and cellular energizer that has been shown to protect the heart against injury. However, its protective effect in the lung is unknown. We therefore set out to study the impact of Coenzyme Q(10) pretreatment in a model of mild and severe lung injury. METHODS: We evaluated the impact of CoQ(10) in a two-stage laboratory study. In the first stage, in order to measure the magnitude of increase in tissue and plasma CoQ(10) following oral therapy we administered high-dose oral CoQ(10) to rats (n = 6). In the second stage we evaluated the impact of CoQ(10) in the rat lung (n = 10) that was subjected to 230 min of normoxic lung injury or 90 min of warm ischaemia and 120 min of reperfusion in a model of lung transplantation. RESULTS: High-dose oral CoQ(10) for 7 days produced a 15-fold increase in plasma and a 3-fold increase in lung CoQ(10). In the normoxic lung, the injury-induced rise in peak airway pressure was reduced by CoQ(10) treatment at 90 min (P = 0.037) and at 120 min (P = 0.005) without any change in arterial oxygen. In the lung subjected to severe ischaemia-reperfusion injury, CoQ(10) did not reduce the injury-induced increase in peak airway pressure (P = 0.599) nor the decrease in arterial oxygen (P = 0.844). However, CoQ(10) markedly reduced the increase in tumour necrosis factor alpha in ischaemic compared with normoxic lung (P = 0.027). CONCLUSIONS: The effect of CoQ(10) pretreatment is insufficient to protect the lung against severe ischaemia-reperfusion as may occur in lung transplantation. However, in the setting of less severe pulmonary injury as in anaesthesia and non-transplant surgery, CoQ(10) may have a protective role. PMID- 20575955 TI - Accuracy of preoperative ultrasound and ultrasound-guided fine needle aspiration cytology for axillary staging in breast cancer. AB - BACKGROUND: The aims of this study were to evaluate the accuracy of preoperative ultrasound and ultrasound-guided fine needle aspiration (FNA) cytology (US-FNAC) for detecting axillary metastases, and to assess how often sentinel node biopsy could be avoided. METHODS: Axillary ultrasound, as a part of routine preoperative staging, was performed in 189 patients with histologically proven breast cancer. US-FNAC was performed on all lymph nodes (LNs) with features suggestive of metastatic disease on ultrasound characteristics and LNs larger than 1 cm regardless of whether the nodes appear normal or abnormal. The cytologic results were compared with the final histological diagnosis. RESULTS: The sensitivity, specificity and positive and negative predictive values of the ultrasound alone of axillary LNs for metastatic breast cancer were 54, 91, 75 and 81%, retrospectively. For the US-FNAC, the respective values were 80, 98, 97 and 84%. CONCLUSIONS: Preoperative axillary ultrasound in combination with US-FNAC provides a simple, minimally invasive and reliable approach to the initial determination of the axillary LN status. Those who are US-FNAC positive can be referred for axillary LN dissection without sentinel LN biopsy. PMID- 20575956 TI - Missed lesions in synchronous multiple gastric cancer. AB - BACKGROUND: The aims of this study were to define differences between synchronous multiple gastric cancer (MGC) and solitary gastric cancer (SGC) and to evaluate the characteristics of missed lesions in MGC so as to improve the detection rate of missed lesions during perioperative procedure. METHODS: The authors retrospectively analysed data on 9157 gastric cancer patients who underwent gastrectomy for gastric cancer in a single hospital. The characteristics of 8893 SGC and 264 MGC patients were evaluated. The characteristics of missed lesions in MGC were compared with those of diagnosed lesions found in preoperative endoscopy. RESULTS: Of the 9157 gastric patients, 264 patients with MGC showed a total of 565 cancer lesions, 70 of which were missed at endoscopy. The patients with MGC demonstrated different characteristics compared with those with SGC in terms of sex, age, type of operation, depth of tumour, lymph node metastasis, tumour size, tumour location and curability (P < 0.05). The characteristics of the missed lesions (n = 70) were a small size (P < 0.05), a middle one-third location (P < 0.001) and a flat type by macroscopic examination (P < 0.05) as compared with detected lesions (n = 495). No survival difference was detected between patients with and without missed lesions over a mean follow-up of 36.0 +/ 22.7 month. CONCLUSIONS: Preoperative gastroscopy should be performed meticulously in the entire stomach, especially in older men, in order to identify the presence and locations of cancer lesions that might otherwise be missed. PMID- 20575957 TI - Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis. AB - AIM: To assess the efficacy and safety of percutaneous transhepatic cholecystostomy (PTC) in treatment for acute cholecystitis in high surgical risk patients. PATIENTS AND METHODS: A retrospective review was carried out from January 1999 to June 2007 on 23 patients, 11 males and 12 females, who underwent PTC for the management of acute cholecystitis at the Department of Surgery, Queen Mary Hospital, Hong Kong, China. The mean age of the patients was 83. They all had either clinical or radiological evidence of acute cholecystitis and had significant pre-morbid diseases. The median follow-up period on them was 35 months. RESULTS: All the PTCs performed were technically successful. One patient died from procedure-related haemoperitoneum, while 87% (n = 20) of all the patients had clinical resolution of sepsis by 20 h after PTC. Eight patients underwent elective cholecystectomy afterwards (62.5% with the laparoscopic approach). Eight patients had dislodgement of the PTC catheter and one of them developed recurrent acute cholecystitis 3 months after PTC. That patient was treated conservatively. Four patients died from their pre-morbid conditions during the follow-up period. CONCLUSION: PTC was a safe and effective alternative for treating acute cholecystitis in this group of patients. Thirteen of them without elective cholecystectomy performed did not have recurrent acute cholecystitis after a single session of PTC. It may be considered as a definitive treatment for this group of patients. PMID- 20575958 TI - Salmonella aortitis--a case of mistaken identity. PMID- 20575959 TI - A case of gastric bronchogenic cyst in Singapore with multiple intrigues. PMID- 20575963 TI - Re: Abdominal giant cystic lymphangioma. PMID- 20575964 TI - Care of admitted trauma patients. PMID- 20575965 TI - Repeat hepatic resection in HCC. PMID- 20575966 TI - Giant gastrointestinal stromal tumour of the oesophagus presenting with atypic symptom. PMID- 20575967 TI - Intussuscepted mucocoele of the appendix secondary to mucinous cystadenoma. PMID- 20575968 TI - Synchronous papillary thyroid carcinoma and right colon cancer. PMID- 20575969 TI - Mesenteric cyst with small bowel volvulus. PMID- 20575970 TI - Ureteral scrotal herniations after renal transplants. PMID- 20575971 TI - Bladder exstrophy. PMID- 20575972 TI - Pancreatic neuroendocrine tumour occurring with Guillian-Barre syndrome. PMID- 20575973 TI - Paediatric Dupuytren's disease. PMID- 20575974 TI - Managing suspicious cervical lymph nodes after thyroidectomy: the utility of hook wire needle localization. PMID- 20575975 TI - Lymphadenectomy at the time of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. AB - OBJECTIVE: To evaluate the incidence of, and predictors for, lymphadenectomy in patients undergoing robot-assisted radical cystectomy (RARC) for bladder cancer. PATIENTS AND METHODS: Utilizing the International Robotic Cystectomy Consortium (IRCC) database, 527 patients were identified who underwent RARC at 15 institutions from 2003 to 2009. After stratification by age group, sex, pathological T stage, nodal status, sequential case number, institutional volume and surgeon volume, logistic regression was used to correlate variables to the likelihood of undergoing lymphadenectomy (defined as >= 10 nodes removed). RESULTS: Of the 527 patients, 437 (82.9%) underwent lymphadenectomy. A mean of 17.8 (range 0-68) lymph nodes were examined. Tumour stage, sequential case number, institution volume and surgeon volume were significantly associated with the likelihood of undergoing lymphadenectomy. Surgeon volume was most significantly associated with lymphadenectomy on multivariate analysis. High volume surgeons (> 20 cases) were almost three times more likely to perform lymphadenectomy than lower-volume surgeons, all other variables being constant [odds ratio (OR) = 2.37; 95% confidence interval (CI) = 1.39-4.05; P = 0.002]. CONCLUSION: The rates of lymphadenectomy at RARC for advanced bladder cancer are similar to those of open cystectomy series using a large, multi-institutional cohort. There does, however, appear to be a learning curve associated with the performance of lymphadenectomy at RARC. PMID- 20575976 TI - Expression of human beta-defensin-2 in the prostate. AB - OBJECTIVE: To investigate the expression and regulation of human beta-defensin-2 (HBD-2) in the prostate. PATIENTS AND METHODS: Normal human prostate epithelial cell line (RWPE-1), human prostate cancer cell lines (DU-145, PC-3), and paraffin embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT-PCR and immunohistochemical staining. HBD-2 expression was also analysed by RT-PCR and ELISA in RWPE-1 cells treated with lipopolysaccharide (LPS). Nuclear factor-kappaB (NF-kappaB) activation was assessed by IkappaBalpha immunoblotting and electrophoretic mobility shift assay (EMSA). RESULTS: BPH tissue and all of the tested prostate cell lines other than PC-3 constitutively express HBD-2 mRNA. HBD-2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages. Exposure to LPS induced HBD-2 upregulation and NF-kappaB activation, as assessed by IkappaBalpha phosphorylation and degradation in RWPE-1 cells. Bay11-7082, an NF-kappaB inhibitor prevented LPS-induced HBD-2 production in RWPE-1 cells. CONCLUSIONS: Prostate epithelial cells may constitutively express HBD-2, and its expression was upregulated by LPS. Our data indicate that HBD-2 may be an important immunomodulatory factor in prostate function. Expression of HBD-2 in normal prostates and the potential role of HBD-2 in prostatitis and BPH should be addressed in the future. PMID- 20575977 TI - Superficial dorsal penile vein thrombosis: a little-known complication of subinguinal varicocelectomy. AB - OBJECTIVE: To describe the symptomatology, diagnosis and treatment of superficial thrombosis of the dorsal penile vein - the most common complication of subinguinal varicocelectomy - and analyse the possible mechanisms involved in the development of the condition. PATIENTS AND METHODS: The clinical records of 326 patients who underwent varicocele repair during the last 10 years was reviewed. The technique used was subinguinal varicocelectomy with arterial preservation. A mini-Doppler probe was used during surgery for artery identification. We report on the postoperative complications of varicocelectomy, with special attention to superficial dorsal penile vein thrombosis, and provide a detailed description of the anatomy of the superficial venous system of the penis. RESULTS: Complications usually associated with varicocele surgery occurred in less than 1% of patients. However, the most common complication in our series was superficial dorsal penile vein thrombosis, which occurred in 2.1% of patients. The use of the mini-Doppler probe allowed us to identify and preserve the arteries in all 326 patients. CONCLUSION: Subinguinal varicocelectomy with intra-operative use of a mini Doppler probe is a rapid and safe technique. The outcomes and complications are similar to those reported for subinguinal microscopic varicocelectomy. Superficial dorsal penile vein thrombosis is a benign self-limited condition whose association with subinguinal varicocelectomy has not been previously reported. PMID- 20575978 TI - Prospective evaluation of combined oncological and functional outcomes after laparoscopic radical prostatectomy: trifecta rate of achieving continence, potency and cancer control at 2 years. AB - OBJECTIVE: To determine the proportion of patients who are continent, potent and cancer-free (trifecta rate) 2 years after extraperitoneal laparoscopic radical prostatectomy (ELRP). PATIENTS AND METHODS: We included patients who underwent an ELRP at our department and who were followed for at least 2 years. Those who were impotent or incontinent before the surgery were excluded from the analysis. Overall, 911 men were included. All patients prospectively completed objective, self-administered questionnaires before the medical visit, concerning their voiding and sexual disorders, before surgery and 12 and 24 months after ELRP. Biochemical recurrence was defined as any detectable serum PSA (>= 0.2 ng/mL). Potency was defined as the ability to achieve an erection sufficient for penetration with or without the use of phosphodiesterase-5 enzyme inhibitor. Urinary continence was defined as absence, or occasional use, of a pad for anticipated vigorous activity. The primary study endpoint was the trifecta rate (cancer control, continence and potency) at 2 years after the surgery. Factors associated with the trifecta outcome were assessed in univariate analysis. RESULTS: Median age and PSA level were 62.2 years and 9.9 ng/mL, respectively. A trifecta outcome was achieved in 29.7 and 54.4% of patients at 12 and 24 months, respectively. The 2-year trifecta rate reached 63.5% in patients undergoing bilateral nerve-sparing surgery and 73.5% in men aged < 60 years. Age < 60 years, PSA level < 10 ng/mL, organ-confined disease and bilateral nerve-sparing procedure were significantly associated with the 2-year trifecta outcome. A total of 84.8% of patients were both cancer-free and continent at 24 months, regardless of erectile function. CONCLUSIONS: Two years after ELRP, the trifecta outcome is achieved in 54.4% of patients who remained potent and continent. This rate reaches 63.5% in patients undergoing a bilateral nerve-sparing procedure. Combined results of good cancer control and continence recovery are reported in 84.8% of patients, regardless of erectile function. PMID- 20575979 TI - Nicorandil-induced penile ulcerations: a case series. AB - OBJECTIVE: To report on the largest series to date of ulceration of the external genitalia, related to treatment with nicorandil - a vasodilator for the prevention and long-term treatment of angina - and to review the literature on the subject, focusing on the clinical features and the pathogenesis of this rare, yet marked, side-effect. PATIENTS AND METHODS: Three patients (aged 71-83 years) were referred for severe ulceration of the penis. A complete work-up was performed to exclude potential underlying causes, including malignancy and sexually transmitted diseases. After a careful review of the patients' medical history, a potentially causal relationship was noted; all patients had been taking nicorandil for at least 2 years before the development of penile ulceration. RESULTS: Penile ulcers associated with nicorandil are characteristically large, deep, painful and have punched-out edges. They usually involve the prepuce or the penile shaft skin. Higher doses of nicorandil (at least 40 mg daily) and surgical procedures seem to increase the risk for nicorandil-related ulceration. Response to topical steroids is poor, but complete healing is achieved by discontinuation of nicorandil, while surgical treatment should be discouraged. CONCLUSION: The growing body of literature showing the link between treatment with nicorandil and ulceration at multiple sites has led to the recognition of this side-effect by the World Health Organization. Nicorandil-related ulcers rarely involve the penile skin and constitute a diagnostic and therapeutic challenge. The pathogenesis of this rare side-effect is largely unknown, but mechanisms such as the 'vascular steal phenomenon' and the direct toxic effect of the drug or its metabolites have been implicated. PMID- 20575980 TI - Early oncological outcomes of robot-assisted radical prostatectomy for high-grade prostate cancer. AB - OBJECTIVE: To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence-free survival (BCRFS) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of >=0.2 ng/mL with a second rising value. The Kaplan-Meier method and log-rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling. RESULTS: The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow-up was 23 (10-46) months and 19 (7-37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS. CONCLUSIONS: Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours. PMID- 20575981 TI - Protective effect of sivelestat, a neutrophil elastase inhibitor, on ipsilateral and contralateral testes after unilateral testicular ischaemia-reperfusion injury in rats. AB - OBJECTIVE: To investigate the effect of a neutrophil elastase inhibitor, sivelestat sodium hydrate, on testicular ischaemia-reperfusion (IR)-injury. MATERIAL AND METHODS: Eight-week-old male Sprague-Dawley rats were divided into four groups: sham-operated control rats; IR rats (group IR); and IR rats that received intra-abdominal administration of 15 mg/kg or 60 mg/kg sivelestat (group IR15 and group IR60, respectively). Right testicular vessels were clamped for 90 min in groups IR, IR15 and IR60. Sivelestat had been administered 45 min after the induction of the ischaemia in groups IR15 and IR60. In subpopulations of IR, IR15 and IR60 rats, reperfusion was performed after ischaemia for 2 h (groups IR A, IR15-A and IR60-A, respectively) or 48 h (groups IR-B, IR15-B and IR60-B, respectively). At the end of the reperfusion period, blood samples were aspirated from both spermatic veins of each rat and testosterone was evaluated. Then both testes from all rats were collected and tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), and heat-shock protein-70(HSP-70) were evaluated. Testicular tissue samples were also processed for histological evaluation and TUNEL staining. RESULTS: MDA, MPO and HSP-70 levels in the ischemic testis were significantly higher in the IR group compared with the control group. MDA and HSP 70 in the contralateral testis were significantly higher in the IR group compared with the control group. Bilateral testosterone levels were lower in all rat groups in comparison with the control group. Bilateral testicular samples in group IR showed extensive histopathologic degenerative alterations and increased percentage of apoptotic cells. Sivelestat treatment lowered the MDA concentration and the percentage of apoptotic cells bilaterally and ameliorated the testicular histological pattern bilaterally. CONCLUSIONS: Unilateral testicular ischaemia causes significant contralateral testicular damage. Sivelestat may be a novel adjunct tool for reducing oxidative stress and partially preventing bilateral testicular damage. PMID- 20575982 TI - Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia. AB - OBJECTIVES: To investigate a possible association between the severity of lower urinary tract symptoms (LUTS) and the serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia (BPH) that underwent surgery for severe benign prostatic obstruction. PATIENTS AND METHODS: In all, 127 selected men with symptomatic BPH attending our urology clinic were recruited. The clinical conditions of BPH were assessed by digital rectal examination, serum prostate specific antigen (PSA) determination, International Prostate Symptom Score (IPSS), transrectal ultrasonography and maximum urinary flow rate (Q(max) ) value at uroflussimetry. Before surgery, we measured the serum concentrations of total testosterone (TT) and free testosterone (FT), oestradiol, prolactin, luteinizing hormone and follicle-stimulating hormone. We excluded men with endocrine diseases, those with prostate disease who were receiving antiandrogen therapy and those with psychological diseases. The relationships between the IPSS score and serum sex hormone levels were determined. RESULTS: The final study population consisted of 122 men (mean age of 70.66 years), as five were excluded (three due to incomplete evaluation and two who were diagnosed with prostate cancer). On statistical analysis, the total IPSS was significantly associated with age (r= 0.405, P < 0.001) and TT (r= 0.298, P= 0.020) but not with FT or the serum levels of the other sex hormones. The serum levels of testosterone and IPSS did not correlate with prostate volume and Q(max) . PSA level and age correlated with prostate volume (r= 0.394, P < 0.001; r = 0.374, P < 0.001, respectively). We distinguished two subgroups of patients: the first group of 40 men with an IPSS of <19 and the second group of 82 with an IPSS of >19, and we evaluated the median levels of TT in each group. There was an increased risk of LUTS in men with a greater serum concentration of TT (P= 0.042), although the mean TT level was in the normal range. CONCLUSIONS: In the present study, the severity of LUTS was associated with age and serum levels of TT but only age correlated with the measures of BPH, especially prostate volume. The potential effects of testosterone on LUTS may well be indirect. Additional large studies are needed to confirm these preliminary results. PMID- 20575983 TI - Urinary incontinence in persons with Prader-Willi Syndrome. AB - OBJECTIVE: To assess and identify the frequency and type of urinary incontinence (UI), as well as associated symptoms in persons with Prader-Willi syndrome (PWS). PWS is characterized by mental retardation, short stature, obesity and hypogonadism. The behavioural phenotype includes eating problems, temper outbursts, affective disorders, stereotypies and speech abnormalities. UI is common in children with mental retardation in general, but has not been reported systematically in children with PWS so far. MATERIALS AND METHODS: The Dutch version of the 'Parental Questionnaire: Enuresis/Urinary Incontinence' was completed by 118 parents of children with PWS. This questionnaire includes items referring to day- and night-time wetting, toilet habits, observable voiding behaviours and reactions, urinary tract infections, stool habits and behavioural symptoms. RESULTS: The rate of nocturnal enuresis in persons with PWS was 13.6% (16) at a mean age of 15.1 years. 3.8% (5) had additional daytime urinary incontinence, and 3.3% (4) had faecal incontinence. Lower urinary tract symptoms were commonly indicative of overactive bladder, dysfunctional voiding and postponement. Also, the rate of internalizing and externalizing behavioural problems was high. CONCLUSION: Urinary incontinence is more common in persons with PWS than in typically developing children, adolescents and adults. As lower urinary tract symptoms are common, detailed assessment and specific treatment of UI should be part of the care of all persons with PWS. PMID- 20575984 TI - Optimizing the detection of subclinical inguinal hernias in men undergoing open radical retropubic prostatectomy. AB - OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and up standing ultrasonography (USUS) for the detection of inguinal hernias (IHs) before open radical retropubic prostatectomy (ORRP) and to assess factors associated with the presence of IHs in these men. PATIENTS AND METHODS: From 1 July 2007 to 1 February 2009, 164 men underwent preoperative evaluation for ORRP by one surgeon. Of these men 113 (69%) were evaluated for IHs by physical examination (PE), USUS and MRI. In all 226 groins were examined. Any IH diagnosed by any method was considered a true positive. The sensitivity, negative predictive value (NPV), and concordance were calculated for the three diagnostic methods. Possible predictive factors of IHs were evaluated. RESULTS: Of the 226 groins evaluated, 72 (32%) IHs were diagnosed. USUS had the greatest sensitivity (69.4%) and the highest NPV (87.5%). MRI had fair agreement with PE and USUS, while USUS and PE had moderate agreement with each other. No factor was associated with an increased likelihood of preoperative diagnosis of IH. CONCLUSIONS: This study was limited by the lack of a reference standard to diagnose IH. USUS was the most sensitive method for the detection of IH. We recommend that all men undergoing ORRP should be evaluated for IHs by PE and at least one imaging method and that IHs be repaired at the time of ORRP, obviating the need for a second surgical procedure. PMID- 20575985 TI - Compromises in data selection in a meta-analysis of biodiversity in managed and unmanaged forests: response to Halme et al. PMID- 20575986 TI - Flawed meta-analysis of biodiversity effects of forest management. PMID- 20575987 TI - Using expert opinion surveys to rank threats to endangered species: a case study with sea turtles. AB - Little is known about how specific anthropogenic hazards affect the biology of organisms. Quantifying the effect of regional hazards is particularly challenging for species such as sea turtles because they are migratory, difficult to study, long lived, and face multiple anthropogenic threats. Expert elicitation, a technique used to synthesize opinions of experts while assessing uncertainty around those views, has been in use for several decades in the social science and risk assessment sectors. We conducted an internet-based survey to quantify expert opinion on the relative magnitude of anthropogenic hazards to sea turtle populations at the regional level. Fisheries bycatch and coastal development were most often ranked as the top hazards to sea turtle species in a geographic region. Nest predation and direct take followed as the second and third greatest threats, respectively. Survey results suggest most experts believe sea turtles are threatened by multiple factors, including substantial at-sea threats such as fisheries bycatch. Resources invested by the sea turtle community, however, appear biased toward terrestrial-based impacts. Results from the survey are useful for conservation planning because they provide estimates of relative impacts of hazards on sea turtles and a measure of consensus on the magnitude of those impacts among researchers and practitioners. Our survey results also revealed patterns of expert bias, which we controlled for in our analysis. Respondents with no experience with respect to a sea turtle species tended to rank hazards affecting that sea turtle species higher than respondents with experience. A more-striking pattern was with hazard-based expertise: the more experience a respondent had with a specific hazard, the higher the respondent scored the impact of that hazard on sea turtle populations. Bias-controlled expert opinion surveys focused on threatened species and their hazards can help guide and expedite species recovery plans. PMID- 20575988 TI - Consequences of buffelgrass pasture development for primary productivity, perennial plant richness, and vegetation structure in the drylands of Sonora, Mexico. AB - In large parts of northern Mexico native plant communities are being converted to non-native buffelgrass (Pennisetum ciliare) pastures, and this conversion could fundamentally alter primary productivity and species richness. In Sonora, Mexico land conversion is occurring at a regional scale along a rainfall-driven gradient of primary productivity, across which native plant communities transition from desert scrub to thorn scrub. We used a paired sampling design to compare a satellite-derived index of primary productivity, richness of perennial plant species, and canopy-height profiles of native plant communities with buffelgrass pastures. We sampled species richness across a gradient of primary productivity in desert scrub and thorn scrub vegetation to examine the influence of site productivity on the outcomes of land conversion. We also examined the influence of pasture age on species richness of perennial plants. Index values of primary productivity were lower in buffelgrass pastures than in native vegetation, which suggests a reduction in primary productivity. Land conversion reduced species richness by approximately 50% at local and regional scales, reduced tree and shrub cover by 78%, and reduced canopy height. Land conversion disproportionately reduced shrub species richness, which reflects the common practice among Sonoran ranchers of conserving certain tree and cactus species. Site productivity did not affect the outcomes of land conversion. The age of a buffelgrass pasture was unrelated to species richness within the pasture, which suggests that passive recovery of species richness to preconversion levels is unlikely. Our findings demonstrate that land conversion can result in large losses of plant species richness at local and regional scales and in substantial changes to primary productivity and vegetation structure, which casts doubt on the feasibility of restoring native plant communities without active intervention on the part of land managers. PMID- 20575989 TI - Costs of integrating economics and conservation planning. AB - Recent literature on systematic conservation planning has focused strongly on economics. It is a necessary component of efficient conservation planning because the question is about effective resource allocation. Nevertheless, there is an increasing tendency toward economic factors overriding biological considerations. Focusing too narrowly on economic cost may lead us back toward solutions resembling those obtained by opportunistic choice of areas, the avoidance of which was the motivation for development of systematic approaches. Moreover, there are many overlooked difficulties in incorporating economic considerations reliably into conservation planning because available economic data and the free market are complex. For instance, economies based on free markets tend to be shortsighted, whereas biodiversity conservation aims far into the future. Although economic data are necessary, they should not be relied on too heavily or considered separately from other sociopolitical factors. We suggest focusing on development of more-comprehensive ecological-economic modeling, while not forgetting the importance of purely biological analyses that are needed as a point of reference for evaluating conservation outcomes. PMID- 20575991 TI - Ethical issues associated with gifts provided to physicians by the pharmaceutical industry. PMID- 20575990 TI - Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa. AB - Salmonella enterica serovar Typhimurium (S. typhimurium) causes a localized enteric infection and its elimination is dependent on a T helper type 1 immune response. However, the mechanism of the protective immune response against the pathogen in gut-associated lymphoid tissue (GALT) at an early stage of the infection is not yet clarified. Here, we show that interleukin-17A (IL-17A) was constitutively expressed in GALT; it was also detected on crypt and epithelial cells of the small intestine. Neutralization of the IL-17A in the intestinal lumen exacerbated epithelial damage induced by intestinal S. typhimurium infection at an early stage of the infection. The result suggests that IL-17A has a pivotal role in the immediate early stage of protection against bacterial infection at the intestinal mucosa. As IL-17A neutralization also suppressed the constitutive localization of beta-defensin 3 (BD3), an IL-17A-induced antimicrobial peptide, at the apical site of the intestinal mucosa, it is estimated that IL-17A constitutively induces the expression of the antimicrobial peptide to kill invading pathogens at the epithelial surface immediately after the infection. In contrast, interferon-gamma is induced around 3 days after S. typhimurium infection, and its expression level increases thereafter. Taken together, the findings lead to the hypothesis that IL-17A participates in the immediate early stage of protection against S. typhimurium intestinal infection whereas interferon-gamma is important at a later stage of the infection. PMID- 20575992 TI - Acute chest syndrome in sickle cell disease. AB - Acute chest syndrome is a common cause of death among patients with sickle cell disease, and an unfamiliar condition to most Australian medical practitioners. We present a case of acute chest syndrome successfully treated with inhaled nitric oxide and exchange transfusion. In the discussion we review current and future management options of acute chest syndrome. PMID- 20575993 TI - Leucocytoclastic and renal vasculitis in a patient with autoimmune pancreatitis: new associations. AB - Autoimmune pancreatitis (AIP) is an uncommon condition which comprises diffuse or discrete pancreatic enlargement and irregular pancreatic duct strictures of autoimmune origin leading to pain or obstructive jaundice associated with extra pancreatic manifestations. It is characterized by an elevated IgG, especially IgG4, level. We illustrate the first described case of a patient with AIP in association with leucocytoclastic and renal vasculitis. PMID- 20575994 TI - Lasthenie de Ferjol syndrome: a rare disease with fascinating history. AB - In our paper, we present the fascinating story of Lasthenie de Ferjol syndrome. A rare self-induced iron deficiency anaemia caused by surreptitious blood-letting. The French haematologist Jean Bernard first described the syndrome and named it after the heroine of Barbey d' Aurevilly's novel The Story without a Name. This factitious anaemia presents a great challenge for physicians even today, both in diagnosis and in therapy. PMID- 20575995 TI - Anaplastic thyroid carcinoma. PMID- 20575996 TI - Giant renal angiomyolipomatosis in association with pulmonary lymphangiomyomatosis. PMID- 20575997 TI - Ventriculo-atrial shunt induced severe pulmonary arterial hypertension: a time for routine screening? PMID- 20575998 TI - Successful rituximab therapy in the treatment of refractory cold haemagglutinin disease with long-term disease control. PMID- 20576002 TI - Abstracts of the 40th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine. April, 232-6, 2010. Auckland, New Zealand. PMID- 20575999 TI - Evaluation and clinical improvement requires responsiveness, scientific method, audit and due process applicable to all. PMID- 20576003 TI - Abstracts of the Australian Rheumatology Association in conjunction with Rheumatology Health Professionals Association 51st Annual Scientific Meeting. Melbourne, Australia. May 22-25, 2010. PMID- 20576004 TI - Interventions for the prevention of overweight and obesity in preschool children: a systematic review of randomized controlled trials. AB - The objective of this study was to analyse interventions for the prevention of overweight and obesity in children under 5 years of age. We carried out a systematic review focusing exclusively on randomized controlled trials (RCTs). Data sources include Medline, Cochrane Library, EMBASE, CINHAL, PsychInfo and Web of Science. Data were extracted from seventeen articles describing seven RCTs identified through electronic search, screening of references in systematic reviews, own files and contact with authors. RCTs were assessed with the Jadad scale. Four trials were carried out in preschool settings, one with an exclusive educational component, two with an exclusive physical activity component and one with both. Two trials were family-based, with education and counselling for parents and children. The remaining trial was carried out in maternity hospitals, with a training intervention on breastfeeding. None of the interventions had an effect in preventing overweight and obesity. The failure to show an effect may be due to the choice of outcomes, the quality of the RCTs, the suboptimal implementation of the interventions, the lack of focus on social and environmental determinants. More rigorous research is needed on interventions and on social and environmental factors that could impact on lifestyle. PMID- 20576005 TI - Melanin and melanogenesis in adipose tissue: possible mechanisms for abating oxidative stress and inflammation? AB - Obesity has become a worldwide epidemic and can lead to multiple chronic diseases. Adipose tissue is increasingly thought to play an active role in obesity-related pathologies such as insulin resistance and non-alcoholic fatty liver disease. Obesity has been strongly associated with systemic inflammation and, to a lesser degree, with oxidative stress, although the causal relationships among these factors are unclear. A recent study demonstrating an expression of the components of the melanogenic pathway and the presence of melanin in visceral adipose has raised questions regarding the possible role of melanogenesis in adipose tissue. As this study also found larger amounts of melanin in the adipose tissue of obese patients relative to lean ones, we hypothesize that melanin, a pigment known for its antioxidant and anti-inflammatory properties, may scavenge reactive oxygen species and abate oxidative stress and inflammation in adipose tissue. This review considers the evidence to support such a hypothesis, and speculates on the role of melanin within adipocytes. Furthermore, we consider whether the alpha-melanocyte-stimulating hormone or its synthetic analogues could be used to stimulate melanin production in adipocytes, should the hypothesis be supported in future experiments. PMID- 20576006 TI - Modern sedentary activities promote overconsumption of food in our current obesogenic environment. AB - Achieving body-weight stability is certainly challenging in today's obesogenic environment. Every day we are surrounded and affected by stimuli that act on our behaviour. A common feature of these stimuli is that they increase our comfort and well-being, but unfortunately they promote a positive caloric balance. Intriguingly, the preponderance of sedentary lifestyles is not only a matter of the amount of calories expended. A careful examination of modern sedentary activities reveals that they also promote overconsumption of food. This is particularly the case with television viewing, video game playing, cognitive working, music listening and short sleeping. Moreover, the increased food intake in the absence of hunger observed with the practice of these modern-life activities emphasizes that the hedonic value of food intake plays an important role. These observations suggest that our quest for reward and pleasure is not fine tuned to our biology, and the development of coping strategies is needed. PMID- 20576007 TI - Abstracts of the Thoracic Society of Australia & New Zealand (TSANZ) and the Australian & New Zealand Society of Respiratory Science (ANZSRS) 2010 Annual Scientific Meetings. Brisbane, Australia. March 19-24, 2010. PMID- 20576008 TI - Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders. AB - BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. STUDY DESIGN AND METHODS: Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through thromboelastometry. RESULTS: Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss. PMID- 20576009 TI - Delayed recovery after autologous peripheral hematopoietic cell transplantation: potential effect of a high number of total nucleated cells in the graft. AB - BACKGROUND: Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored. STUDY DESIGN AND METHODS: A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean+1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time. RESULTS: Sixteen patients, who received at least 3 * 10(6) CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p=0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1beta, and IL-6 involved in stem cell homing. CONCLUSION: Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation. PMID- 20576010 TI - Expanded evaluation of blood donors in the United States for human immunodeficiency virus type 1 non-B subtypes and antiretroviral drug-resistant strains: 2005 through 2007. AB - BACKGROUND: In a previous study of 66 human immunodeficiency virus (HIV)-infected US blood donors from 1999 to 2005, HIV-1 non-B and antiretroviral drug-resistant strains accounted for 4.7 and 6.5% of HIV infections, respectively. This study was expanded to include an additional 11 recently acquired infections and 197 established infections collected from January 2005 through December 2007. STUDY DESIGN AND METHODS: HIV-infected donors were detected using FDA-licensed assays. Drug resistance profiles for protease and reverse transcriptase (RT) genes were determined using a genotyping system (ViroSeq, Celera Diagnostics); genetic subtype was determined by phylogenetic analysis of these sequences. RESULTS: Drug resistance profiles were obtained for 203 of 208 specimens; 9.9% had mutations that confer drug resistance. Ten showed resistance to a single drug class: nine to nonnucleoside RT inhibitors (NNRTIs) and one to nucleoside RT inhibitors (NRTIs). Eight showed two drug class resistance: five NRTI plus NNRTI, two NRTI plus protease inhibitor (PI), and one NNRTI plus PI. Two showed three drug class resistance. Non-B strains were identified in 2.5% of donors and consisted of subtypes A1 and D, CRF02_AG, CRF43-02G, and URF_BF. CONCLUSIONS: Data from this and the previous study show that antiretroviral drug-resistant HIV-1 is present in 9.1% of HIV-infected donors from 1999 through 2007; 9.3% of established infections and 6.9% of recent infections. Diverse HIV-1 non-B strains presently account for 3.0% of HIV infections in US donors. PMID- 20576011 TI - Misleading hepatitis B test results due to intravenous immunoglobulin administration: implications for a clinical trial of rituximab in immune thrombocytopenia. AB - BACKGROUND: Rituximab may cause reactivation of hepatitis B virus (HBV) even in patients with remote HBV infection. Thus, the presence of hepatitis B core antibodies (anti-HBc) was an exclusion criterion for a randomized trial of rituximab for patients with immune thrombocytopenia. A high seroprevalence of anti-HBc observed among patients screened for the trial prompted this substudy to investigate for an association between anti-HBc seropositivity and exposure to intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: This was a retrospective case-control study that was a substudy of a randomized controlled trial. RESULTS: Of 24 trial participants screened at one center, 11 (45.8%) were anti-HBc positive and of those, 10 (90.0%) had received IVIG in the preceding 4 weeks. Of 13 seronegative patients screened, five (38.5%) had received IVIG (odds ratio, 16; 95% confidence interval, 1.5-166.1). Seven (70%) of 10 seropositive participants subsequently reverted to negative upon repeat testing. Serial testing before and after IVIG (n = 2) demonstrated transient anti-HBc that lasted for up to 11 weeks after the last dose of IVIG. Samples from three of five different IVIG products were found to contain anti-HBc. CONCLUSIONS: Passive transfer of anti-HBc from certain IVIG products may lead to misinterpretation of hepatitis test results with implications for treatment and clinical trial eligibility. To avoid misleading test results, anti-HBc should be measured before or 3 months after IVIG administration; alternatively an IVIG product known to be free of anti-HBc should be used. PMID- 20576012 TI - A novel RHCE*ce 48C, 733G allele with Nucleotide 941C in Exon 7 encodes an altered red blood cell e antigen. AB - BACKGROUND: Several RHCE*ce alleles have in common a 733C>G (Leu245Val) change. Some encode an altered expression of e on red blood cells (RBCs) and individuals with such RBCs can make e-like alloantibodies. The identification of an apparent anti-hr(B) in the serum of an E-e+ African American patient prompted us to analyze her DNA, which revealed a novel RHCE*ce allele. We also screened blood samples from African Americans to determine the frequency of the novel allele. STUDY DESIGN AND METHODS: Hemagglutination tests and molecular analyses were performed by standard procedures. RESULTS: Analysis of the proband's DNA revealed RHCE*ce 48C/C, 733G/G, 941T/C, and 1006G/T. Of 272 samples from African Americans, 257 were RHCE*941T/T (wild type), and 15 (6%) were RHCE*941T/C. Of these 15, 14 were RHCE*ce/ce, 10 with 733C/G and four with 733G/G, and one was RHCE*ce/cE, 733C/G. Cloning experiments confirmed the Nucleotide 941 change and showed that 48C, 733G, 941C, and 1006T were carried on the same allele. RBCs from the 15 samples carrying the RHCE*941C variant typed V/VS+ and hrB+W. CONCLUSION: This study identifies a novel allele, RHCE*ce 48C, 733G, 941C, 1006T which is predicted to encode 16Cys, 245Val, 314Ala, and 336CyS and was shown to encode c, V/VS, and an altered expression of e and hrB antigens. The clinical significance of the antibody found in the proband is not established because E+e- RBC components were transfused to the patient. The novel RHCE*ce 48C, 733G, 941C, 1006T allele was present in 5.5% of samples from African Americans and thus, in this small cohort, it had a frequency of 0.028. PMID- 20576013 TI - Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab. AB - Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS. This review of the literature focuses on the role of rituximab, a chimeric monoclonal antibody directed against CD20 antigen expressed by B lymphocytes, in patients with relapsing or refractory TTP-HUS with or without ADAMTS-13 deficiency, suggesting that rituximab may produce clinical remission in a significant proportion of patients. Rituximab therapy reduces plasma requirement and avoids complications related to salvage immunosuppressive therapy. In conclusion, rituximab provides an effective, well tolerated, and safe treatment option for patients with idiopathic TTP-HUS, thus giving an alternative approach to the current treatment based on PE. PMID- 20576014 TI - Granulocyte antibody screening: evaluation of a bead-based assay in comparison with classical methods. AB - BACKGROUND: Granulocyte antibodies have been implicated in allo- and autoimmune neutropenia and in transfusion reactions. STUDY DESIGN AND METHODS: Fifty-one sera from suspected alloimmune neutropenia or transfusion-related acute lung injury (TRALI) and 40 sera from suspected autoimmune neutropenia were tested for granulocyte antibodies using LABScreen MULTI (One Lambda, Inc.), compared with classical tests (flow cytometry [FC] and granulocyte agglutination [GAT] followed by monoclonal antibody-specific immobilization of granulocyte antigens [MAIGA]). RESULTS: In alloimmune situations, 48 sera were concordant (94%), two sera positive for HNA with LABScreen MULTI were negative by FC/GAT and/or MAIGA, and one serum sample negative for HNA with LABScreen MULTI was positive by classical tests. In autoimmune neutropenia, 30 sera were concordant (75%), four sera positive for HNA with LABScreen MULTI were negative by FC/GAT and/or MAIGA, and six sera negative for HNA with LABScreen MULTI were positive by FC/GAT and/or MAIGA. For detection of autoantibodies, the LABScreen MULTI was less concordant. However, with the exception of one case, the discrepancies were observed in sera that did not show a clear specificity. CONCLUSIONS: LABScreen MULTI correlated well with our classical methods for HNA-1 and HNA-2a antibody screening. It can be used for screening blood donors or patients suspected of TRALI, but GAT is still needed for HNA-3a antibody screening. PMID- 20576015 TI - A practical strategy to reduce the risk of passive hemolysis by screening plateletpheresis donors for high-titer ABO antibodies. AB - BACKGROUND: Hemolytic transfusion reactions (HTRs) can occur from ABO incompatible platelet (PLT) transfusions. After a series of cases at our institution, a procedure to screen all plateletpheresis donors for high-titer ABO antibodies was implemented. STUDY DESIGN AND METHODS: Plasma samples from plateletpheresis donors were screened using pooled 0.8% A1 and 0.8% B red blood cells (RBCs) in buffered gel. Dilutions of 1 in 150, 1 in 200, and 1 in 250 were sequentially evaluated. A component testing positive for high-titer ABO antibodies was restricted to ABO-identical or group O recipients or washed. RESULTS: At the initial dilution of 1 in 150, half of group O components were labeled as high titer. At the current dilution of 1 in 250, 25% of group O components are labeled as high titer. No PLT-associated HTR has been reported since screening began. CONCLUSION: Universal screening for high-titer ABO antibodies in plateletpheresis donors can be implemented efficiently to reduce the risk of HTRs. The cutoff for classifying a unit as high titer depends on the serologic method used and may be customized by the individual facility. Our screening method uses one gel test per donation regardless of blood group and a plasma dilution of 1 in 250 with pooled A1/B RBCs in buffered gel. PMID- 20576016 TI - The appropriateness and physician compliance of platelet usage by a computerized transfusion decision support system in a medical center. AB - BACKGROUND: The prescribing of inappropriate platelet (PLT) transfusions is always a significant problem. A computerized transfusion decision support system (CTDSS) has been used in Kaohsiung Medical University Hospital since September 2004. In this study, the physician compliance and appropriateness of PLT usage after using the CTDSS were investigated. STUDY DESIGN AND METHODS: A total of 5887 PLT transfusion episodes between January and December 2008 were reviewed including the demographic data and the "true reason" for each transfusion practice. The pre- and posttransfusion PLT counts were retrieved. The physician compliance, the appropriateness of PLT usage, and the PLT increments after transfusion were investigated. RESULTS: Physician compliance was 85.4%, and the appropriateness of PLT usage was 69.6%. The most commonly chosen indication from the CTDSS was "prophylactic use, PLT count <=20*10(9) /L." The highest inappropriate order rate was from the emergency department. More than half of the inappropriate episodes were from the surgery unit. The inappropriate rates were significant in terms of both different order sources and functional units (p<0.0001). The posttransfusion PLT counts increased in two-thirds of the episodes, and most of them were with the pretransfusion PLT counts of less than 50*10(9) /L. CONCLUSIONS: In Taiwan, the PLT concentration is too low-priced and this might cause the overuse of blood components. Under the global budget of National Health Insurance, preventing the overuse of blood components might serve as one of the mechanism to improve medical quality. The CTDSS should be more powerful and effective to intervene in the appropriateness of transfusion practice. PMID- 20576017 TI - Enhanced classification of Chagas serologic results and epidemiologic characteristics of seropositive donors at three large blood centers in Brazil. AB - BACKGROUND: A major problem in Chagas disease donor screening is the high frequency of samples with inconclusive results. The objective of this study was to describe patterns of serologic results among donors to the three Brazilian REDS-II blood centers and correlate with epidemiologic characteristics. STUDY DESIGN AND METHODS: The centers screened donor samples with one Trypanosoma cruzi lysate enzyme immunoassay (EIA). EIA-reactive samples were tested with a second lysate EIA, a recombinant-antigen based EIA, and an immunfluorescence assay. Based on the serologic results, samples were classified as confirmed positive (CP), probable positive (PP), possible other parasitic infection (POPI), and false positive (FP). RESULTS: In 2007 to 2008, a total of 877 of 615,433 donations were discarded due to Chagas assay reactivity. The prevalences (95% confidence intervals [CIs]) among first-time donors for CP, PP, POPI, and FP patterns were 114 (99-129), 26 (19-34), 10 (5-14), and 96 (82-110) per 100,000 donations, respectively. CP and PP had similar patterns of prevalence when analyzed by age, sex, education, and location, suggesting that PP cases represent true T. cruzi infections; in contrast the demographics of donors with POPI were distinct and likely unrelated to Chagas disease. No CP cases were detected among 218,514 repeat donors followed for a total of 718,187 person-years. CONCLUSION: We have proposed a classification algorithm that may have practical importance for donor counseling and epidemiologic analyses of T. cruzi-seroreactive donors. The absence of incident T. cruzi infections is reassuring with respect to risk of window phase infections within Brazil and travel-related infections in nonendemic countries such as the United States. PMID- 20576018 TI - Platelet quality after washing: the effect of storage time before washing. AB - BACKGROUND: Patients who have experienced anaphylactic transfusion reactions receive washed platelet (PLT) concentrates (PCs) where the plasma has been substituted with a PLT additive solution. This study compares the in vitro quality of PCs washed at the beginning of the storage period (Day 1) to PCs washed at the end of storage (Day 7). STUDY DESIGN AND METHODS: PLTs were prepared by the buffy coat procedure. Two concentrates were pooled and then split to obtain an identical pair of PCs. One of the PCs was washed with T-Sol on Day 1 and the other on Day 7 of storage. Swirling, blood gases, and metabolic variables were analyzed before washing. Analyses of surface expression of CD62P and coagulation by free oscillation rheometry (FOR) were performed before and after washing. RESULTS: pH was acceptable in all PCs. Washing on Days 1 and 7 increased the CD62P surface expression. The FOR variables clotting time and clot retraction were not influenced by washing on either day. Washing resulted in a decrease in the number of PLTs and the decrease was larger on Day 7 compared to Day 1. CONCLUSIONS: PLTs washed on Days 1 and 7 of storage are effected by washing in a similar manner. However, a larger loss of PLTs occurred during washing on Day 7. PMID- 20576020 TI - Incidence and clinical significance of bacterial and fungal contamination of the preservation solution in liver transplantation. AB - A perfusion fluid used in the preservation of the grafted liver represents a medium suitable for microorganism growth. In this observational study, a sample of 232 transplanted livers was collected. Perfusion fluid samples were stored for microbiological analysis from harvested donors. Bacteria were isolated in 91 out of 232 samples, post-operative infections related to contaminated perfusion solution occurred in 13 cases. The contamination rate of the preservation medium appears to be high, but postoperative infections occurs rarely. We suggest periodic detection and a protocol in place designed for antibiotic use for transplanted patients exposed to contaminated perfusion solution. PMID- 20576019 TI - Choice of induction regimens on the risk of cytomegalovirus infection in donor positive and recipient-negative kidney transplant recipients. AB - BACKGROUND: Late occurrence of cytomegalovirus (CMV) infection remains a concern in CMV-seronegative kidney and/or pancreas transplant recipients of CMV seropositive organs (donor positive/recipient negative, D+/R-) despite the use of prophylaxis. We investigated the impact of various antibody induction regimens on CMV infection in this group of patients. METHODS: A total of 254 consecutive D+/R kidney and/or pancreas transplant patients were studied. The induction agents rabbit anti-thymocyte globulin (rATG) or basiliximab were used according to the center practice. All patients received prophylaxis with valganciclovir (VGCV) for either 3 or 6 months. The occurrence of CMV infection was confirmed by positive DNA viremia. Multivariate Cox regression analyses were performed to determine risk factors for CMV infection. RESULTS: The cumulative incidence of CMV infection was 58, 112, and 59 cases per 1000 patient-years for patients who received no antibody induction, induction with rATG, or basiliximab induction, respectively (P=0.02). The use of rATG but not basiliximab was associated with an increased risk for CMV infection (adjusted hazard ratio [AHR] 2.13, 95% confidence interval [CI] 1.24-3.54, P=0.006). Acute rejection and its treatment with rATG were not associated with an increased risk for CMV infection when an additional course of VGCV was given following the treatment. Longer duration of prophylaxis was associated with a reduced risk for CMV infection (AHR 0.54, 95% CI 0.33-0.87, P=0.011). CONCLUSIONS: Induction with rATG is associated with increased risk of CMV infection. Longer duration of prophylaxis is beneficial. PMID- 20576021 TI - Seronegative naturally acquired West Nile virus encephalitis in a renal and pancreas transplant recipient. AB - West Nile virus (WNV), a single-stranded RNA flavivirus, has spread across the United States since arriving in 1999. While asymptomatic or self-limited in a majority of patients, WNV can cause a severe neuroinvasive disease, which occurs more often in transplant recipients with chronic immunosuppression. Diagnosis of acute WNV infection usually relies on serologic identification of immunoglobulin M (IgM) specific for the virus. We report a fatal case of naturally acquired WNV encephalitis in a renal and pancreas transplant recipient who was seronegative for WNV-specific IgM but had detectable WNV RNA by nucleic acid amplification testing (NAAT) several weeks after the onset of symptoms. This case demonstrates the importance of using both serologic assays and NAAT for WNV in transplant recipients with the clinical suspicion of encephalitis. PMID- 20576022 TI - A nationwide survey for prevalence of hepatitis E virus antibody in qualified blood donors in Japan. AB - BACKGROUND AND OBJECTIVES: In previous studies, we reported the transmission of hepatitis E virus (HEV) by transfusion, and the frequent detection of HEV markers in Japanese blood donors with elevated ALT levels. For the current study, we carried out a nationwide survey of the prevalence of IgG anti-HEV in qualified blood donors throughout Japan. MATERIALS AND METHODS: The 12,600 samples from qualified blood donors were collected from seven blood centres (1800 per centre) representing nearly all regions of Japan. Samples were from age- and sex-matched blood donors who tested negative for all the current blood screening tests. The samples were screened using the in-house IgG anti-HEV ELISA. Sequentially, the positive samples were tested by the commercial IgG anti-HEV ELISA. RESULTS: Of 12,600 samples, 431 (3.4%) were regarded as positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in eastern Japan (5.6%) than in western Japan (1.8%) (P<0.001), and was also age-dependent and higher in men (3.9%) than in women (2.9%) (P=0.002). CONCLUSION: The spread of the domestic infection of HEV was observed in qualified blood donors in Japan. A higher prevalence of IgG anti-HEV was observed in male donors, older donors and in donors residing in eastern Japan. Further studies are necessary to clarify the potential risk of transfusion-transmission of HEV in Japan. PMID- 20576023 TI - Payment, compensation and replacement--the ethics and motivation of blood and plasma donation. AB - The supply of blood and plasma to produce haemotherapies varies around the world, but all environments need donors to furnish the raw material. Many countries still lack adequate supply, and the question of what amounts of blood and plasma are required for optimal treatment is still unresolved. The issue of compensating donors has been a controversial and emotive one in blood transfusion for many decades. Donors are conventionally classified as paid, voluntary or replacement, and a level of stigma, based on safety and ethical considerations, has been attached to paid donation. This review points to evidence which renders many of these concerns redundant. Purist arguments against compensated donation have little basis in evidence and would lead to many of today's voluntary donors being designated as paid, because of the large range of incentives used to recruit and retain them. Misplaced application of 'Titmussian' volunteerism has precipitated its own safety and supply problems. Current systems of compensation and replacement are needed to maintain supplies of essential products and lead to safe products in controlled environments. We propose that a plurality of routes towards donation is an appropriate paradigm in the heterogeneous landscape of blood and plasma product supply. PMID- 20576024 TI - The epidemiology of red cell transfusion. AB - BACKGROUND AND OBJECTIVES: Understanding of the clinical usage of red cells is limited despite its importance in transfusion practice improvement and planning for blood supply requirements. Previous studies have described red cell use based upon ICD and hospital discharge codes; however, such approaches are open to misclassification. This study addresses this limitation by undertaking an epidemiological analysis of red cell use using case note review. MATERIALS AND METHODS: Patient, disease and contextual factors were extracted from the medical records of a randomly selected sample of hospital patients in Northern Ireland who received a red cell transfusion during 2005 (n=1474). RESULTS: Transfused patients received a total of 3804 units (median of two units per transfusion episode). Most transfusions occurred in a medical setting (71%). Patients undergoing treatment for gastrointestinal conditions were responsible for the majority of the demand (29% of transfusion episodes; 34% of red cell units). The presence of bleeding and abnormal tests of coagulation were associated with receiving larger transfusions (>= 3 units), while patients undergoing orthopaedic surgery and those with a haemoglobin level over 7 g/dl had the lowest risk of receiving >= 3 units in any one transfusion episode. CONCLUSION: The majority of red cells are now prescribed in a medical setting. With an ageing population and increasing therapeutic interventions, the demand for blood is likely to increase despite efforts to reduce usage by eliminating inappropriate transfusions through education and behaviour change. The post-transfusion target (and therefore the number of units to transfuse) for any given clinical situation as well as guidance on a 'safe' transfusion threshold should be considered in future guidelines. PMID- 20576025 TI - Storage of Buffy-coat-derived platelets in additive solutions: in vitro effects on platelets prepared by the novel TACSI system and stored in plastic containers with different gas permeability. AB - BACKGROUND: The novel TACSI system is designed for automated preparation of platelets (PLTs) from pooled buffy coats (BCs). One TACSI device will handle 6 units at the same time. The aim of our in vitro study is to investigate the effects of using this automated equipment with subsequent storage in two different plastic containers and to compare these results with PLTs prepared by the OrbiSac system. STUDY DESIGN AND METHODS: Buffy-coat-derived PLTs (n=8) were prepared by using the TACSI system, including storage in polyvinyl chloride (PVC) based plastic containers with di, n-decyl phthalate (DnDP) (TACSI R) and BTHC (TACSI T)-based plasticizers. As a reference, the OrbiSac System was used to prepare PLTs (n=8) with subsequent storage in a PVC plastic container with a citrate-based plasticizer (BTHC). In total, 16 TACSI and eight reference units, supplied by approximately 30% plasma and 70% SSP+, were analysed for various in vitro variables during the 7-day storage period. RESULTS: No significant difference in PLT counts, LDH, mean platelet volume (MPV) and adenosine triphosphate between the groups was detected. Glucose was lower (P<0.05) and lactate was higher (P<0.05) in TACSI R vs. OrbiSac. With exception of day 7 (P<0.05 TACSI R vs. OrbiSac), HSR reactivity were not different between groups. Extent of shape change was lower and CD62P higher in TACSI T when compared with TACSI R and OrbiSac units (P<0.05). pH was maintained at >6.8 (day 7) and swirling remained at the highest level (score=2) for all units throughout storage. CONCLUSION: Platelets prepared by the TACSI system with subsequent storage in two different PVC-based plastic containers were equivalent to reference PLTs with regard to in vitro characteristics during 7 days of storage. PMID- 20576026 TI - The application of the National Institute of Clinical Excellence guidelines for treatment of metastatic renal cell carcinoma in the United Kingdom: friend or foe? PMID- 20576027 TI - WT1 is not a reliable marker to distinguish reactive from neoplastic astrocyte populations in the central nervous system. AB - A diagnostic difficulty in neuropathology practice is distinguishing reactive from neoplastic astrocyte populations. This is particularly true in small biopsy samples that lack evidence of increased cellularity or mitotic activity, microvascular proliferation, or necrosis. We performed the current study to validate the previously reported finding that in the central nervous system, the expression of WT1 is limited to neoplastic astrocytes. We retrospectively studied WT1 protein expression by immunohistochemistry (IHC) in 100 formalin-fixed, paraffin-embedded brain tissue samples consisting of 3 normal control tissues, 44 cases of reactive gliosis, 49 gliomas and 4 lesions suspicious for glioma. In normal human cortex, WT1 staining was restricted to vascular endothelium. Most cases of reactive gliosis (82%) showed at least focal WT1 positivity, and analysis of specimens with electrode monitoring lesions showed an inverse relationship between WT1 expression intensity and the number of days from electrode placement to tissue resection. All glioma samples (100%) and all cases suspicious for glioma (100%) showed at least focal WT1 positivity. Our results likely differ from those in the prior report because of differences in tissue fixation and IHC methodology. Thus, our findings indicate that WT1 expression alone is not a reliable feature to distinguish reactive from neoplastic astrocytes. PMID- 20576028 TI - Are invaders different? A conceptual framework of comparative approaches for assessing determinants of invasiveness. AB - What determines invasiveness of alien organisms is among the most interesting and urgent questions in ecology. In attempts to answer this question, researchers compare invasive alien species either to native species or to non-invasive alien species, and this is done in either the introduced or native ranges. However, inferences that can be drawn from these comparisons differ considerably, and failure to recognize this could hamper the search for determinants of invasiveness. To increase awareness about this issue, we present a framework of the various comparisons that can be used to test for determinants of invasiveness, and the specific questions each comparison can address. Moreover, we discuss how different comparisons complement each other, and therefore should be used in concert. For progress in invasion biology, it is crucial to realize that different comparisons address different biological questions and that some questions can only be answered unambiguously by combining them. PMID- 20576030 TI - Opposing effects of competitive exclusion on the phylogenetic structure of communities. AB - Though many processes are involved in determining which species coexist and assemble into communities, competition is among the best studied. One hypothesis about competition's contribution to community assembly is that more closely related species are less likely to coexist. Though empirical evidence for this hypothesis is mixed, it remains a common assumption in certain phylogenetic approaches for inferring the effects of environmental filtering and competitive exclusion. Here, we relate modern coexistence theory to phylogenetic community assembly approaches to refine expectations for how species relatedness influences the outcome of competition. We argue that two types of species differences determine competitive exclusion with opposing effects on relatedness patterns. Importantly, this means that competition can sometimes eliminate more different and less related taxa, even when the traits underlying the relevant species differences are phylogenetically conserved. Our argument leads to a reinterpretation of the assembly processes inferred from community phylogenetic structure. PMID- 20576029 TI - An integrative approach to understanding microbial diversity: from intracellular mechanisms to community structure. AB - Trade-offs have been put forward as essential to the generation and maintenance of diversity. However, variation in trade-offs is often determined at the molecular level, outside the scope of conventional ecological inquiry. In this study, we propose that understanding the intracellular basis for trade-offs in microbial systems can aid in predicting and interpreting patterns of diversity. First, we show how laboratory experiments and mathematical models have unveiled the hidden intracellular mechanisms underlying trade-offs key to microbial diversity: (i) metabolic and regulatory trade-offs in bacteria and yeast; (ii) life-history trade-offs in bacterial viruses. Next, we examine recent studies of marine microbes that have taken steps toward reconciling the molecular and the ecological views of trade-offs, despite the challenges in doing so in natural settings. Finally, we suggest avenues for research where mathematical modelling, experiments and studies of natural microbial communities provide a unique opportunity to integrate studies of diversity across multiple scales. PMID- 20576031 TI - A neuronal substrate for a state-dependent modulation of sensory inputs in the brainstem. AB - Central networks modulate sensory transmission during motor behavior. Sensory inputs may thus have distinct impacts according to the state of activity of the central networks. Using an in-vitro isolated lamprey brainstem preparation, we investigated whether a brainstem locomotor center, the mesencephalic locomotor region (MLR), modulates sensory transmission. The synaptic responses of brainstem reticulospinal (RS) cells to electrical stimulation of the sensory trigeminal nerve were recorded before and after electrical stimulation of the MLR. The RS cell synaptic responses were significantly reduced by MLR stimulation and the reduction of the response increased with the stimulation intensity of the MLR. Bath perfusion of atropine prevented the depression of sensory transmission, indicating that muscarinic receptor activation is involved. Previous studies have shown that, upon stimulation of the MLR, behavioral activity switches from a resting state to an active-locomotor state. Therefore, our results suggest that a state-dependent modulation of sensory transmission to RS cells occurs in the behavioral context of locomotion and that muscarinic inputs from the MLR are involved. PMID- 20576032 TI - Serotonin fibre sprouting and increase in serotonin transporter immunoreactivity in the CA1 area of hippocampus in a triple transgenic mouse model of Alzheimer's disease. AB - Alzheimer's disease (AD) is a neurodegenerative disease that deteriorates cognitive functions and associated brain regions such as the hippocampus, being the primary cause of dementia. Serotonin (5-HT) is widely present in the hippocampus, being an important neurotransmitter involved in learning and memory. Although recent evidence suggests alterations in 5-HT neurotransmission in AD, it is not clear how hippocampal 5-HT innervation is modified. Here, we studied hippocampal 5-HT innervation by analysing: (i) the expression, density and distribution of 5-HT transporter (SERT)-immunoreactive fibres; (ii) the specific morphological characteristics of serotonergic fibres and their relation to amyloid plaques; and (iii) the total number of 5-HT neurons within the raphe nuclei in triple transgenic mouse model of AD. We used quantitative light microscopy immunohistochemistry comparing transgenic and non-transgenic animals of different ages (3, 6, 9, 12 and 18 months). The transgenic animals showed a significant increase in SERT fibres in the hippocampus in a subfield-, strata- and age-specific manner. The increase in SERT fibres was specific to the CA1 stratum lacunosum-moleculare. An increase in SERT fibres in transgenic animals was observed at 3 months (by 61%) and at 18 months (by 74%). No changes, however, were found in the total number of raphe 5-HT neurons at any age. Our results indicate that triple transgenic mice display changes in the expression of SERT and increased SERT fibres sprouting, which may account for imbalanced serotonergic neurotransmission associated with (or linked to) AD cognitive impairment. PMID- 20576033 TI - RapGAPs in brain: multipurpose players in neuronal Rap signalling. AB - Small Rap guanosine-tri-phosphate (GTP)ases are crucially involved in many cellular processes, including cell proliferation, differentiation, survival, adhesion and movement. In line, it has been shown that Rap signalling is involved in various aspects of neuronal differentiation, like the establishment of neuronal polarity or axonal growth cone movement. Rap GTPases can be activated by a wide variety of external stimuli, and this is mediated by specific guanine nucleotide exchange factors (RapGEFs). Inactivation of RapGTP can be achieved with the aid of specific GTPase-activating proteins (RapGAPs). In the brain, the most prominent RapGAPs are Rap1GAP and those of the spine-associated RapGAP (SPAR) family. This latter family consists of three members (SPAR1-3), from which two of them, namely SPAR1 and 2, have been investigated in more detail. As such, the localization of RapGAPs is crucially important in regulating Rap signalling at various sites in the cell and, for both SPAR1 and 2, enrichment at synaptic sites has been demonstrated. In recent years particularly the role of SPAR1 in shaping dendritic spine morphology has attracted considerable interest. In this review we will summarize the described actions of different RapGAPs expressed in the brain, and we will focus in particular on the SPAR family members. PMID- 20576034 TI - HPC-1/syntaxin 1A gene knockout mice show abnormal behavior possibly related to a disruption in 5-HTergic systems. AB - HPC-1/syntaxin 1A (STX1A) is thought to regulate the exocytosis of synaptic vesicles in neurons. In recent human genetic studies, STX1A has been implicated in neuropsychological disorders. To examine whether STX1A gene ablation is responsible for abnormal neuropsychological profiles observed in human psychiatric patients, we analysed the behavioral phenotype of STX1A knockout mice. Abnormal behavior was observed in both homozygotes (STX1A(-/-)) and heterozygotes (STX1A(+/-)) in a social interaction test, a novel object exploring test and a latent inhibition (LI) test, but not in a pre-pulse inhibition test. Interestingly, attenuation of LI, which is closely related to human schizotypic symptoms, was restored by administration of the selective serotonin reuptake inhibitor, fluoxetine, but not by the dopamine reuptake inhibitor, GBR12935, or the noradrenalin reuptake inhibitor, desipramine. We also observed that LI attenuation was restored by DOI (a 5-HT(2A) receptor agonist), but not by 8-OH DPAT (a 5-HT(1A) receptor agonist), mCPP (a 5-HT(2C) receptor agonist), SKF 38393 (a D(1) receptor agonist), quinpirole (a D(2)/D(3) receptor agonist) or haloperidol (a D(2)/D(3) receptor antagonist). Thus, attenuation of LI is mainly caused by disruption of 5-HT-ergic systems via 5-HT(2A) receptors. In addition, 5 HT release from hippocampal and hypothalamic slices was significantly reduced. Therefore, ablation of STX1A may cause disruption of 5-HT-ergic transmission and induce abnormal behavior. PMID- 20576035 TI - Narcoleptic orexin receptor knockout mice express enhanced cholinergic properties in laterodorsal tegmental neurons. AB - Pharmacological studies of narcoleptic canines indicate that exaggerated pontine cholinergic transmission promotes cataplexy. As disruption of orexin (hypocretin) signaling is a primary defect in narcolepsy with cataplexy, we investigated whether markers of cholinergic synaptic transmission might be altered in mice constitutively lacking orexin receptors (double receptor knockout; DKO). mRNA for Choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and the high-affinity choline transporter (CHT1) but not acetylcholinesterase (AChE) was significantly higher in samples from DKO than wild-type (WT) mice. This was region-specific; levels were elevated in samples from the laterodorsal tegmental nucleus (LDT) and the fifth motor nucleus (Mo5) but not in whole brainstem samples. Consistent with region-specific changes, we were unable to detect significant differences in Western blots for ChAT and CHT1 in isolates from brainstem, thalamus and cortex or in ChAT enzymatic activity in the pons. However, using ChAT immunocytochemistry, we found that while the number of cholinergic neurons in the LDT and Mo5 were not different, the intensity of somatic ChAT immunostaining was significantly greater in the LDT, but not Mo5, from DKO than from WT mice. We also found that ChAT activity was significantly reduced in cortical samples from DKO compared with WT mice. Collectively, these findings suggest that the orexins can regulate neurotransmitter expression and that the constitutive absence of orexin signaling results in an up-regulation of the machinery necessary for cholinergic neurotransmission in a mesopontine population of neurons that have been associated with both normal rapid eye movement sleep and cataplexy. PMID- 20576037 TI - Congenital heart disease--a journal for young investigators, fellows, and residents. PMID- 20576036 TI - Adenosine A1 and A2A receptors are not upstream of caffeine's dopamine D2 receptor-dependent aversive effects and dopamine-independent rewarding effects. AB - Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade-induced conditioned place preferences. These aversive effects are mediated by the dopamine D(2) receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A(2A) receptor is important for caffeine's physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A(2A) receptor knockout mice showed stronger dopamine-dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine-independent and A(2A) receptor-independent preferences. Additionally, the A(1) receptor, alone or in combination with the A(2A) receptor, does not seem to be important for caffeine's rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade-induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine's appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning. PMID- 20576038 TI - The long road to better ACHD care. AB - The care of adult patients with congenital heart defects in the United States is spotty at best, and needs to improve greatly if the needs of these patients are to be met. The care of American children with congenital heart defects is generally excellent. Pediatric cardiac services are well established and well supported. The care of adults with congenital heart disease (CHD) is well established in only a few American centers. While there are an increasing number of clinics, they are generally poorly resourced with relatively few patients. If located in adult cardiology programs, they are usually minor players. If located in pediatric cardiac programs, they are usually minor players as well. Training programs for adult CHD (ACHD) caregivers are few, informal, and poorly funded. To improve the situation, we need perhaps 25 well-resourced and well-established regional ACHD centers in the United States. We need to stop the loss to care of CHD patients at risk of poor outcomes. We need to educate patients and families about the need for lifelong and skilled surveillance and care. We need to effect an orderly transfer from pediatric to adult care. We need to strengthen the human resource infrastructure of ACHD care through the training and hiring of healthcare professionals of a quality equivalent to those working in the pediatric care environment. We need to demonstrate that adult care is high quality care. We need more high-quality ACHD research. The ACHD community needs to establish its credibility with pediatric cardiac providers, adult cardiology groups, with governments, with professional organizations, and with research funding agencies. Accordingly, there is a need for strong political action on behalf of American ACHD patients. This must be led by patients and families. These efforts should be supported by pediatric cardiologists and children's hospitals, as well as by national professional organizations, governments, and health insurance companies. The goal of this political action should be to see that ACHD patients can receive high-quality lifelong surveillance, that we lose fewer patients to care, and that the staff and other services needed are available nationwide. PMID- 20576039 TI - The long road--a destination not yet reached. PMID- 20576041 TI - Evaluating the safety of high-altitude travel in patients with adult congenital heart disease. AB - As medical management and surgical techniques continue to improve, patients with congenital heart disease are surviving further into adulthood and seeking to participate in multiple activities. Given the increasing popularity of adventure recreation, it is likely that many of these individuals will express interest in travel to and activities at high altitude. At first glance, the hypoxia associated with acute altitude exposure would appear to pose high risks for patients with underlying cardiopulmonary disease, but few studies have systematically addressed these concerns in the adult congenital heart disease population. In this review, we consider the safety of high-altitude travel in these patients. After reviewing the primary cardiopulmonary responses to acute hypoxia and the risks of high altitude in all individuals regardless of their underlying health status, we consider the risks in adult congenital heart disease patients, in particular. We focus on broad concerns that should be considered in all patients such as whether they have underlying pulmonary hypertension, the adequacy of their ventilatory responses, and their ability to compensate for hypoxemia and right-to-left shunting. We then conclude by providing basic recommendations for pretravel assessment in patients with congenital heart disease of moderate or great complexity. PMID- 20576040 TI - Update on tetralogy of Fallot for the adult cardiologist including a brief historical and surgical perspective. AB - There has been a steady rise in the prevalence of severe congenital heart disease (CHD) in adults because of improved treatment and survival during childhood. This has resulted in a shift in CHD morbidity and mortality beyond 18 years of age. The healthcare community must be prepared to meet this new challenge. Adult cardiologists need to be aware of common CHD, such as tetralogy of Fallot (TOF), as they will encounter adults with this CHD in their practice. With routine monitoring, cardiac imaging, early intervention, and treatment as highlighted in this report, continued improvement in the long-term fitness and avoidance of late complications for adult TOF patient is anticipated. PMID- 20576042 TI - Hybrid procedures: adverse events and procedural characteristics--results of a multi-institutional registry. AB - INTRODUCTION: Procedural cooperation between cardiac surgeon and interventional cardiologist to facilitate interventions such as device delivery or angioplasty (hybrid procedure) has become increasingly common in the management of patients with congenital heart disease. DESIGN: Data were prospectively collected using a multicenter registry (C3PO). Between February 2007 and December 2008, seven institutions submitted data regarding 7019 cardiac catheterization procedures. Procedural data and adverse events (AEs) of 128 hybrid procedures were evaluated. RESULTS: There was significant variability in the number of hybrid procedures per center, ranging from one to 89 with a median of eight. A total of 60% of interventional (vs. strictly diagnostic) hybrid procedures were performed by one center. The median weight was 3.7 kg (0.7-86 kg). Single-ventricle circulation was present in 60% of the procedures. Hybrid procedures included: patent ductus arteriosus (PDA) stent placement (n = 55), vascular rehabilitation (n = 25), ventricular septal defect (VSD) device closure (n = 7), valvotomy (n = 3), and diagnostic hybrid procedures (n = 38). Sixteen AEs occurred in 15/128 (12%) procedures. These included minor or trivial AEs (n = 9), moderate AEs (n = 5), major AEs (n = 1), and catastrophic AEs (n = 1). The type of AE documented included arrhythmias (n = 6), hypoxia or hypotension (n = 3), vessel or cardiac trauma (n = 2), and other events (n = 5). Of documented AEs, 9/16 (56%) were classified as not preventable, 6/16 (38%) as possibly preventable, and 1/16 (6%) as preventable. The incidence of AE related to PDA stent placement with surgical exposure (5/50, 10%) was significantly lower when compared with PDA stent placement performed percutaneously (4/5, 80%, P= .002). CONCLUSION: Hybrid procedures appear to have a low incidence of associated major AEs. PDA stent placement performed as a palliation of hypoplastic left heart syndrome (HLHS) or complex single/two ventricle patients may have a lower incidence of AEs if performed using a direct approach with surgical exposure rather than a percutaneous approach. Accurate definitions of these innovative procedures are required to facilitate prospective data collection. PMID- 20576043 TI - B-type natriuretic peptide: perioperative patterns in congenital heart disease. AB - OBJECTIVE: B-type natriuretic peptide (BNP) has diagnostic, prognostic, and therapeutic roles in adults with heart failure. BNP levels in children undergoing surgical repair of congenital heart disease (CHD) were characterized broadly, and distinguishable subgroup patterns delineated. DESIGN: Prospective, blinded, observational case series. SETTING: Academic, tertiary care, free-standing pediatric hospital. PATIENTS: Children with CHD; controls without cardiopulmonary disease. Interventions. None. MEASUREMENTS: Preoperative cardiac medications/doses, CHD lesion types, perioperative BNP levels, intraoperative variables (lengths of surgery, bypass, cross-clamp), postoperative outcomes (lengths of ventilation, hospitalization, open chest; averages of inotropic support, central venous pressure, perfusion, urine output; death, low cardiac output syndrome (LCOS), cardiac arrest; readmission; and discharge medications). RESULTS: Median BNP levels for 102 neonatal and non-neonatal controls were 27 and 7 pg/mL, respectively. Serial BNP measures from 105 patients undergoing CHD repair demonstrated a median postoperative peak at 12 hours. The median and interquartile postoperative 24-hour average BNP levels for neonates were 1506 (782-3784) pg/mL vs. 286 (169-578) pg/mL for non-neonates (P < 0.001). Postoperative BNP correlated with inotropic requirement, durations of open chest, ventilation, intensive care unit stay, and hospitalization (r = 0.33-0.65, all P < 0.001). Compared with biventricular CHD, Fontan palliations demonstrated lower postoperative BNP (median 150 vs. 306 pg/mL, P < 0.001), a 3-fold higher incidence of LCOS (P < 0.01), and longer length of hospitalization (median 6.0 vs. 4.5 days, P= 0.01). CONCLUSIONS: Perioperative BNP correlates to severity of illness and lengths of therapy in the CHD population, overall. Substantial variation in BNP across time as well as within and between CHD lesions limits its practical utility as an isolated point-of-care measure. BNP commonly peaks 6-12 hours postoperatively, but the timing and magnitude of BNP elevation demonstrates notable age-dependency, peaking earlier and rising an order of magnitude higher in neonates. In spite of higher clinical acuity, non-neonatal univentricular CHD paradoxically demonstrates lower BNP levels compared with biventricular physiologies. PMID- 20576044 TI - Early pleural effusions related to the myocardial injury after open-heart surgery for congenital heart disease. AB - OBJECTIVES: The degree of effusion immediately after cardiopulmonary bypass (CPB) can vary and may reflect several factors including the degree of myocardial injury. We compared the degree of pleural effusions after CPB to the overall myocardial injury as determined by serum cardiac troponin I (cTnI) levels after elective repair of a variety of congenital heart defects, including univentricular surgeries via cavopulmonary shunts. METHODS: Serum was collected pre-CPB, post-CPB, and daily after that and cTnI level measured. The postoperative pleural effusion was measured each day until the chest tube was removed. Results. The 21 study patients were of average age of 5.5 years (+/ 5.6). The duration of chest-tube drainage after open-heart surgery was 4.3 days (+/-3.5) and the amount was 2.4 mL/kg/hour (+/-2.9). For the biventricular repairs, cTnI levels on the postoperative day (POD) 1 best correlated with amount of effusion (n = 16, r = 0.5, P = 0.02) and the average (POD 0-3) cTnI levels with the total duration (n = 16, r = 0.4, P = 0.01) and also the amount (n = 16, r = 0.5, P = 0.02) of effusions. For the cavopulmonary shunts, the post-CBP cTnI level best correlated with the duration (n = 5, r = 0.8, P = 0.02) and amount (n = 5, r = 0.9, P = 0.02) of effusions. A cTnI level on the first postoperative day >or=15 microg/L was associated with effusions >2 days (sensitivity of 81% and specificity of 80%). CONCLUSION: We found that higher the cTnI released, especially >or=15 microg/L, longer the duration and greater the amount of early pleural effusions for a variety of congenital heart surgeries including cavopulmonary shunts. A number of factors may lead to excessive pleural effusions and the degree of myocardial injury may be one of them. PMID- 20576045 TI - Early and midterm results of an alternative procedure to homografts in primary repair of truncus arteriosus communis. AB - BACKGROUND: Repair of truncus arteriosus communis (TAC) in the neonatal and early infant period has become a standard practice. We report our experience on primary repair of TAC with a bovine pericardial-valved woven Dacron conduit as an alternative procedure to homografts, with a focus on early and midterm results. METHODS: From January 2001 to December 2007, 15 patients with mean age 1.5 years (range 3 months to 8 years), underwent primary repair of simple TAC. Cases with cardiogenic shock, complex-associated cardiac lesions, or adverse anatomy of the truncal valve were excluded. The Collett and Edwards anatomical type classification of TAC was as follows: type I, 13 (87%); and type II, 2 (13%). Right ventricular outflow tract was reconstructed in all the cases with a bovine pericardial-valved woven Dacron conduit. RESULTS: Overall mortality was 6.6% (1 death due to severe pulmonary hypertension). At a mean follow-up of 31 months (range 6-51), there were no deaths (5-year actuarial survival 93.4%). Out of the 14 midterm survivors, three developed stenosis of the pericardial-valved woven Dacron conduit, but only one underwent interventional procedure including percutaneous balloon dilation with stenting for associated left pulmonary artery hypoplasia. The rate of patients with no surgical or percutaneous reinterventions performed because of obstruction of the right ventricular outflow tract reconstruction in the midterm (5 years) was 86%. CONCLUSIONS: Truncus arteriosus communis repair with a bovine pericardial-valved woven Dacron conduit can be performed with a very low perioperative mortality and satisfactory midterm morbidity, favorably compared with that reported for the use of homografts. Interventional cardiac catheterization may delay the time of reoperation for inevitable conduit replacement due to stenosis. PMID- 20576046 TI - Right ventricular function in congenital heart defects assessed by regional wall motion. AB - OBJECTIVES: To develop a simple method to assess right ventricular function by angiography. BACKGROUND: Conventional methods of evaluating right ventricular function are inaccurate, cumbersome, and expensive. METHODS: We analyzed biplane right ventricular angiograms taken in the posterior-anterior and lateral projections using software to measure right ventricular volumes and regional wall motion in 78 patients with normal hearts (n = 29), atrial septal defects (ASD n = 13), pulmonary valve stenosis (PVS n = 21), and postoperative atrial switch patients (n = 15). We also measured the shortening fraction (SF) from the midtricuspid annulus to the septum and correlated various angiographic measurements with the right ventricular (RV) ejection fraction. RESULTS: The volume-overloaded patients (ASD) had larger end diastolic volumes and increased SF compared with normal patients, while the pressure-loaded patients (PVS) had normal volumes and SF. The postoperative atrial switch patients had decreased systolic function and increased end diastolic volume. The SF for all of the patients correlated with the ejection fraction (r= 0.785, Por= 250 during the 90 days preceding the event compared to 32.4% of those who did not (odds ratio: 23.13, p < 0.01). A log fold increase in the BNP value compared to the baseline median BNP is a risk for cardiac death in the subsequent 90-day period (OR: 6.82, 95% confidence interval: 1.25-37.11, p = 0.03). CONCLUSION: Routine BNP monitoring in the post-cardiac transplant pediatric patient allows for the determination of a median BNP, which can be used as a baseline. A log fold increase from the median BNP, or a BNP value >or= 250, increases the risk of death or re-transplant and suggests a 90-day period of heightened clinical surveillance, perhaps necessitating increased medication or re-listing for repeat transplant. PMID- 20576051 TI - Development of factor V and thrombin inhibitors in children following bovine thrombin exposure during cardiac surgery: a report of three cases. AB - Factor V and thrombin inhibitors may develop following exposure to bovine thrombin preparations. In patient populations where exposure to bovine thrombin is common, such as children undergoing cardiovascular surgery, the development of such inhibitors should be considered in the evaluation of prolonged prothrombin times. We present three cases of children developing factor V and thrombin inhibitors following repeated exposure during cardiac surgical procedures. PMID- 20576052 TI - Atresia of the superior vena cava causing cyanosis and increasing head circumference in an infant. AB - We report a case of congenital atresia of the superior vena cava (SVC) with stenotic anastomoses between systemic and pulmonary veins, resulting in cyanosis and symptoms consistent with SVC syndrome in an infant. PMID- 20576053 TI - Induction of left ventricular fascicular tachycardia with transesophageal pacing in a toddler. AB - J.V. is a 3(1/2)-year-old patient with left ventricular fascicular ventricular tachycardia that had been well controlled on verapamil for 3 years. He was taken for a transesophageal electrophysiology study prior to discontinuing medication in an attempt to induce his tachycardia. We report the use of transesophageal electrophysiology study as a noninvasive method to induce left ventricular fascicular ventricular tachycardia in a toddler. PMID- 20576054 TI - Double aortic arch with aortic atresia and left-sided type B interruption. AB - Aortic valve atresia with interruption of the aortic arch is an extremely rare anomaly; only eleven cases of this anomaly have been reported to date. In the absence of additional sources of blood flow to the ascending aorta, aortic valve atresia with interruption of the aortic arch is fatal. We present, to the best of our knowledge, the first case of a live birth with aortic valve atresia and interrupted left aortic arch (type B) without evidence of an aorticopulmonary communication or ductal supply to the native ascending aorta. Instead, blood flow to the native aortic root was derived from a persistent right embryonic dorsal aorta. PMID- 20576055 TI - Refractory progression of coronary aneurysms, a case of delayed onset Kawasaki disease as depicted by cardiac computed tomography angiography. AB - BACKGROUND: Kawasaki disease (KD) is an immune-mediated vasculitis of unknown etiology with self-limited clinical course that was first described in 1967 by Dr. Tomisaku Kawasaki. It is a disease of early childhood and rare past late adulthood but one that can have detrimental consequences when there is a delay in diagnosis and treatment. Cardiovascular complications causing increased morbidity and mortality may include coronary artery aneurysms, myocardial infarction, heart failure, arrhythmias, and peripheral artery occlusion. CASE PRESENTATION: Here, we present an atypical case of delayed onset KD in a young teenager. DS had visited three different emergency departments during the course of 2 weeks for unrelenting fevers. Despite multiple treatment protocols including immunoglobulin, steroids, and tumor necrosis factor-alpha antagonists, he continued to have progression of cardiovascular complications. While echocardiographic findings were suspicious for cardiac complications, a cardiac computed tomography (CT) angiography was able to clearly distinguish giant coronary aneurysms. CONCLUSION: Without prompt therapy, fever and manifestations of acute inflammation can last for several weeks to months with increased risk toward complications. The incidence of coronary artery aneurysms has been noted to be 25% in untreated patients with a mortality rate of up to 2%. Using low-dose protocols along with high spatial and temporal resolution of cardiac CT angiography may provide a useful and complimentary imaging modality in accurate diagnosis and follow-up of patients with KD. PMID- 20576056 TI - Anomalous origin of the left coronary artery from the right pulmonary artery presenting following relief of left heart obstruction: a distinct and predictable clinico-pathological syndrome. AB - INTRODUCTION: Pre-operative recognition of significant abnormalities of the coronary arteries is important in a variety of congenital cardiac conditions. Failure to diagnose anomalous origin of the coronary artery from the pulmonary artery during repair of other anomalies is important because reduction in pulmonary artery pressure will reduce myocardial perfusion pressure. PATIENTS: We report two cases of the rare association of anomalous origin of the left coronary artery from the right pulmonary artery, aortic coarctation, and mitral stenosis. CONCLUSIONS: Definitive imaging of coronary artery anatomy by echocardiography or other modalities should form a routine part of diagnostic assessment in all congenital heart disease patients but particularly those with left heart obstruction. PMID- 20576060 TI - Health checks in primary care for adults with intellectual disabilities: how extensive should they be? AB - BACKGROUND: Routine health checks have gained prominence as a way of detecting unmet need in primary care for adults with intellectual disabilities (ID) and general practitioners are being incentivised in the UK to carry out health checks for many conditions through an incentivisation scheme known as the Quality and Outcomes Framework (QOF). However, little is known about the data being routinely recorded in such health checks in relation to people with ID as practices are currently only incentivised to keep a register of people with ID. The aim of this study was to explore the additional value of a health check for people with ID compared with standard care provided through the current QOF structure. METHODS: Representative practices were recruited using a stratified sampling approach in four primary care trusts to carry out health checks over a 6-month period. The extracted data were divided into two aggregated informational domains for the purpose of multilevel regression analysis: 'ID-specific' (containing data on visual assessment, hearing assessment, behaviour assessment, bladder function, bowel function and feeding assessment) and financially incentivised QOF targets (blood pressure, smoking status, ethnicity, body mass index, urine analysis and carer details) which are incentivised processes. RESULTS: A total of 651 patients with ID were identified in 27 practices. Only nine practices undertook a health check on 92 of their patients with ID. Significant differences were found in the recorded information, between those who underwent a health check and those who did not (P < 0.001, chi(2) = 56.3). In the group that had health check, recorded information was on average higher for the 'QOF targets' domain, compared with the 'ID-specific' domain, by 58.7% (95% CI: 54.1, 63.3, P < 0.001). CONCLUSIONS: If incentives are to be used as a method for improving care for people with ID through health checks a more targeted approach focused on ID-specific health issues might be more appropriate than an extensive health check. PMID- 20576061 TI - Humour appreciation and comprehension in children with intellectual disability. AB - BACKGROUND: Data on typically developing children show that humour development starts from an early age. Studies investigating humour in children with intellectual disability (ID) are few and have generally focused on identifying differences between this population and other groups of children. This study focuses on children with ID as a heterogeneous group and seeks to answer the following questions: (1) what kinds of humour do children with ID appreciate most in a video cartoon? (2) How does the mode of presentation of jokes influence humour comprehension? METHOD: This study examines humour appreciation and comprehension in school-aged children (n = 9; chronological age: 7-11 years) with mild/moderate ID. Specific tools were developed to explore each aspect. Participants rated short scenes from a video cartoon to show their appreciation for different kinds of humour. A set of video-recorded jokes, with different modes of presentation, were used in the comprehension task. RESULTS: The greatest appreciation was expressed for physical and visual humour. Non-specific scenes (i.e. scenes with no particularly funny elements) were also rated highly. Jokes presented with gesture were understood more than jokes told without supports. These differences in comprehension, arising from supported/unsupported jokes, were statistically significant within the group studied. CONCLUSIONS: The context of humour (e.g. being part of a video cartoon) is important in determining what children with ID find funny. The significant difference in comprehension brought about by a change in mode of presentation (i.e. supported/unsupported joke telling) suggests that humour comprehension can be facilitated. PMID- 20576062 TI - Placement, relocation and end of life issues in aging adults with and without Down's syndrome: a retrospective study. AB - BACKGROUND: Aging adults with Down's syndrome (DS) experience more relocations and other life events than adults with intellectual disabilities aged 50 and older without DS. Age-related functional decline and the higher incidence of dementia were implicated as the contributing factors that led to relocation and nursing home placement. METHOD: A retrospective study of adults with intellectual disabilities who were born prior to the year 1946 was conducted to analyse the number of relocations experienced over a 5- and 10-year period. The cohort consisted of 140 individuals (61 with DS between ages 50-71 years, and 79 without DS between ages 57-89 years) who had been referred to a diagnostic and research clinic. RESULTS: Analyses revealed the number of relocations over a 5- and 10 year period were significantly greater in the DS group. Placement in a nursing home for end of life care was significantly higher in the DS group whereas the majority (90%) in the non-DS group remained in a group home setting. Mortality was significantly earlier in the DS group with the mean age at death to be 61.4 years compared with 73.2 years in the non-DS group. CONCLUSIONS: The present results suggest that aging adults with DS encounter more relocations, and are more likely to have their final placement for end of life care in a nursing home. In contrast, the adults without DS were subjected to less relocation and remained in the same group home setting. PMID- 20576063 TI - Loss of response to melatonin treatment is associated with slow melatonin metabolism. AB - BACKGROUND: In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this loss of response is associated with slow melatonin metabolism. METHOD: In this study, we determined melatonin clearance in two female (aged 61 and 6 years) and one male (aged 3 years) patients who had chronic insomnia, late melatonin onset and mild ID, and whose sleep quality worsened a few weeks after initial good response to melatonin treatment, suggesting melatonin tolerance. After a 3-week washout period, patients received melatonin 1.0, 0.5 or 0.1 mg, respectively. Salivary melatonin level was measured just before melatonin administration, and 2 and 4 h thereafter. After this melatonin clearance test, melatonin treatment was resumed with a considerably lower dose. RESULTS: In all patients melatonin concentrations remained >50 pg/mL at 2 and 4 h after melatonin administration. After resuming melatonin treatment sleep problems disappeared. The same procedure was followed in three patients who did not show loss of response to melatonin after 6 months of treatment. In all patients in the control group melatonin concentrations decreased between 2 and 4 h after melatonin administration with a mean of 83%. CONCLUSION: We hypothesise that loss of response to melatonin treatment can be caused by slow metabolisation of exogenous melatonin. As melatonin is metabolised in the liver almost exclusively by cytochrome P450 enzyme CYP1A2, this slow melatonin metabolism is probably due to decreased activity/inducibility of CYP1A2. In patients with loss of response to melatonin, a melatonin clearance test should be considered and a considerably dose reduction is advised. PMID- 20576064 TI - A parent training model for toilet training children with autism. AB - BACKGROUND: Azrin & Foxx pioneered an intensive toilet training protocol for individuals with intellectual disability living in a residential setting. Since the development of the Rapid Toilet Training (RTT) protocol, many have replicated the efficacy, most notably in educational and outpatient treatment settings, but often training over longer periods of time. This study presents data from a parent training model that replicates Azrin and Foxx's results and training time. METHOD: This multiple baseline across subjects design study employs an ABA design where two boys diagnosed with autism were toilet trained using a modified Azrin & Foxx intensive teaching protocol. The first subject, a 4-year-old boy, did not have a history of attempted toilet training. The second subject, a 6-year-old boy, demonstrated a history of failed toilet training attempts in both the home and school settings. The trainings were conducted in the home setting where a novel parent-training approach was implemented. RESULTS: Participant 1 was continent at the end of the second day of training, and completely toilet trained (including initiation and communication) by day 10 of the intervention. Participant 2 was continent after day 1 and completely toilet trained by day 5 of the intervention. CONCLUSIONS: Long-term follow-up demonstrates maintenance of skills 3 years post training. Social validity via parent satisfaction was assessed. Limitations to the current study and recommendations for future research were discussed. PMID- 20576065 TI - A comparison of intellectual assessments over video conferencing and in-person for individuals with ID: preliminary data. AB - BACKGROUND: Video conferencing (VC) technology has great potential to increase accessibility to healthcare services for those living in rural or underserved communities. Previous studies have had some success in validating a small number of psychological tests for VC administration; however, VC has not been investigated for use with persons with intellectual disabilities (ID). A comparison of test results for two well known and widely used assessment instruments was undertaken to establish if scores for VC administration would differ significantly from in-person assessments. METHOD: Nineteen individuals with ID aged 23-63 were assessed once in-person and once over VC using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Beery-Buktenica Test of Visual-Motor Integration (VMI). RESULTS: Highly similar results were found for test scores. Full-scale IQ on the WASI and standard scores for the VMI were found to be very stable across the two administration conditions, with a mean difference of less than one IQ point/standard score. CONCLUSION: Video conferencing administration does not appear to alter test results significantly for overall score on a brief intelligence test or a test of visual-motor integration. PMID- 20576066 TI - Transforming maternity care. PMID- 20576067 TI - Human papillomavirus and cervical cancer knowledge, health beliefs, and preventative practices in older women. AB - OBJECTIVE: To explore knowledge of Human Papillomavirus (HPV) and cervical cancer, health beliefs, and preventative practices in women 40 to 70 years. DESIGN: Cross-sectional descriptive. SETTING: Three urban ambulatory Obstetrics and Gynecology offices connected with a teaching hospital's Department of Obstetrics and Gynecology in the Mid-Atlantic section of the United States. PARTICIPANTS: A convenience sample of 149 women age 40 to 70. METHODS: To assess HPV and cervical cancer knowledge, health beliefs, and preventative practices a self-administered survey, the Awareness of HPV and Cervical Cancer Questionnaire was distributed to women as they waited for their well-woman gynecologic exam. RESULTS: The mean knowledge score was 7.39 (SD=3.42) out of 15. One third of the questions about the relationship of HPV and risks for cervical cancer were answered incorrectly by more than 75% of these women. Although most appreciate the seriousness of cervical cancer, they believed themselves not particularly susceptible. CONCLUSION: There is a need for HPV and cervical cancer awareness and education for women older than age 40. Women's health care professionals are well positioned to act as a catalyst to improve HPV and cervical cancer knowledge, health beliefs, and preventative practice to ensure optimum health promotion for all women. PMID- 20576068 TI - Predictors of crying problems in the early postpartum period. AB - OBJECTIVE: To investigate maternal and infant factors associated with midwife reported crying problems in the early postpartum period. DESIGN: Case control study. SETTING: Postnatal home care in Switzerland. PARTICIPANTS: Seven thousand seven hundred and sixty-five mother/child dyads who received postnatal homecare by midwives (n=1,636 cases of midwife-reported crying problems, n=6,129 controls). METHODS: We investigated factors associated with infant crying problems during the postpartum period as documented in the Statistical Database of Independent Midwives' Services in Switzerland (2007). Using case control methodology, we matched all identified cases of crying problems with controls who had been cared for by the same midwife. A conditional logistic regression model was used to analyze the associations of reported crying problems with maternal and infant factors. RESULTS: Maternal health and mood problems in the immediate postpartum period were significantly associated with reported crying problems. Maternal health and mood problems included physical complications after birth, psychological decompensation, and depression. Further risk factors for infant crying problems were planned resumption of paid work directly after paid maternity leave (at 15-16 weeks postpartum) and immigrant status. A protective effect was observed for higher parity. CONCLUSIONS: Crying problems in the early postpartum period are associated with mothers' physical, psychological, and social conditions. Care practices that promote new mothers' physical and psychological recovery after birth could be a promising strategy to prevent early crying problems. Specific support is important for mothers with early signs of depression or decompensation, intention to return early to paid work, immigrant background, and for first-time mothers. PMID- 20576069 TI - Health behavior in adolescent women reporting and not reporting intimate partner violence. AB - OBJECTIVE: To determine similarities and differences between adolescent women reporting intimate partner violence (IPV) and/or forced sexual intercourse (FSI) and those not reporting these experiences on a series of health-enhancing and health-compromising behaviors. DESIGN AND SETTING: Secondary analysis of the 2001 Youth Risk Behavior Survey conducted in high schools throughout the United States. PARTICIPANTS: One thousand six hundred and eight female students among whom 450 reported no IPV or FSI, 457 reported IPV, 473 reported FSI, and 228 reported experiencing IPV and FSI. METHODS: Descriptive statistics and discriminant function analysis. RESULTS: Statistical analyses revealed that the groups of adolescent women experiencing IPV and FSI were more alike than disparate, so groups were combined for further analysis. Results reveal that adolescent women reporting IPV and FSI are more likely to participate in health compromising behaviors and less likely to participate in health-enhancing behaviors. CONCLUSION: Adolescent women reporting either IPV or forced sex are more likely to be engaging in risky behaviors and less likely to be engaged in health-enhancing behaviors. These findings have important implications for health care professionals who care for adolescent women. PMID- 20576070 TI - Are race and ethnicity risk factors for breech presentation? AB - OBJECTIVE: To investigate race and ethnicity as risk factors for breech presentation. DESIGN: Case-control study using a population-based birth certificate registry that included linkage to Medicaid/Women, Infants, & Children (WIC) eligibility data for a socioeconomic proxy variable. SETTING: Florida, USA. PARTICIPANTS: 912,107 mothers of singletons born in Florida 1999 to 2003. METHODS: Maternal race and ethnicity were evaluated as risk factors for breech presentation using logistic regression. The dependent variable was birth presentation. Covariates were variable measures that have been repeatedly identified as risk factors for breech presentation in the literature and are known to be highly accurate birth certificate variable measures. RESULTS: White women were 69% more likely to have a breech baby (adjusted odds ratio [OR]=1.69, 95% confidence interval [CI] 1.63, 1.76) than Black women. Higher socioeconomic status was a risk factor in the bivariate analyses, but not in the adjusted analysis. Prematurity, nulliparity, female infant, and advancing maternal age were risk factors in the final model. The final model accounted for <5% of the total variance (Max Rescaled R(2)=4.18%), and thus was poorly fit (Hosmer and Lemeshow goodness of fit <0.0001). CONCLUSIONS: White women were at increased risk of having a breech baby. However, important variables appear to be missing from the model. PMID- 20576071 TI - Prediction of perineal trauma during childbirth by assessment of striae gravidarum score. AB - OBJECTIVE: To explore the association between striae gravidarum (SG) and the risk for perineal trauma (PT) in childbirth. DESIGN: A cross-sectional study. SETTING: Maternity ward in 5 university medical centers. PARTICIPANTS: Three hundred and eighty-five women (28.9+/-5.3 years old) who delivered vaginally. METHODS: Striae gravidarum score was assessed using the Atwal numerical scoring system. The association was examined between PT as the outcome measure, defined by tears or laceration, and the total striae scores (TSS) obtained at the abdomen, hips, buttocks, and breast. RESULTS: Significantly higher TSS scores were found in women with PT compared with women without PT (3.60+/-0.39 vs. 2.31+/-0.23, p=.003). Specifically, striae scores at the breast and hips were significantly higher among women who had PT. Logistic regression analysis revealed that TSS (OR=0.079; 95% CI 1.012, 1.151; p=.021), as well as a rise in body mass index (BMI) during pregnancy (OR=1.025; 95% CI 1.001, 1.049; p=.043) are significant predictors of PT. CONCLUSIONS: This study demonstrates a significant relation between SG and PT. The findings suggest that SG assessment may be used in the clinical setting by midwives and nurses as a simple and noninvasive tool to better define women at risk for PT. PMID- 20576072 TI - Previous birth experience in women with intense fear of childbirth. AB - OBJECTIVE: To describe the meaning of previous experiences of childbirth in pregnant women who have exhibited intense fear of childbirth such that it has an impact on their daily lives. DESIGN: A descriptive phenomenological study. SETTING: A maternity clinic for women with fear of childbirth in the western part of Sweden. PARTICIPANTS: Nine women with intense fear of childbirth who were pregnant with their second child and considered their previous birth experiences negative. METHODS: Interviews that were transcribed verbatim and analyzed with a reflective life-world approach. RESULTS: The essential meanings that emerged were a sense of not being present in the delivery room and an incomplete childbirth experience. The women felt as if they had no place there, that they were unable to take their place, and that even if the midwife was present, she did not provide support. The experience remained etched in the women's minds and gave rise to feelings of fear, loneliness, and lack of faith in their ability to give birth and diminished trust in maternity care. These experiences contrasted with brief moments that made sense. CONCLUSIONS: Previous childbirth experiences for pregnant women with intense fear of childbirth have a deep influence and can be related to suffering and birth trauma. The implication is to provide maternity care where the nurse/midwife is present and supports women during birth in a way that enables them to be present and take their place during birth. PMID- 20576073 TI - The effects of Qi exercise on maternal/fetal interaction and maternal well-being during pregnancy. AB - OBJECTIVE: To investigate the effects of Qi exercise on maternal outcomes during pregnancy. DESIGN: A prospective, two-group, quasi-experimental, pretest/post test design was used. SETTING: A convenience sample was recruited from one women's wellness center and one women's health clinic in Seoul, Korea. PARTICIPANTS: Participants were healthy pregnant women at more than 18 weeks gestation. A total of 70 women were included in the final analysis. METHODS: Qi exercise was carried out for 90 minutes, twice a week for 12 weeks. Study outcomes were measured by the Intrapersonal Communication Questionnaire (Talking to Your Baby), Zung's Self-rating Depression Scale (ZSDS), the State Trait Anxiety Inventory (STAI), and the Pregnancy Mild Discomfort Index. Analysis of covariance was used to compare outcomes between groups, after adjusting for baseline scores. RESULTS: The Qi exercise group had higher post test maternal/fetal interaction and lower maternal depressive symptoms and physical discomfort scores than the control group. There was no difference in anxiety. CONCLUSION: The findings suggest that the holistic approach of Qi exercise may positively influence maternal/fetal interaction and mother's health. Whether these beneficial effects can be sustained throughout pregnancy requites additional research. PMID- 20576074 TI - Social justice in maternal/infant care. PMID- 20576075 TI - Foundations for social justice-based actions in maternal/infant nursing. AB - The purpose of this article is to discuss health disparities and inequities and their most significant effects on maternal/infant health. A literature background on the social context of justice and distinct ethical theories is provided. Different ethical approaches to guide interventions that can improve the health of mothers and infants are presented. By adopting an ethical framework of social justice, nurses can better understand and thus influence outcomes and ameliorate health disparities and inequalities. PMID- 20576076 TI - Identifying health disparities and social inequities affecting childbearing women and infants. AB - This article presents health disparities and social inequities that may underlie adverse outcomes for childbearing women and infants in the United States. It also presents Internet-accessible databases that nurses can use to assess maternal and infant health disparities at a national or state level. Such assessments are basic to planning programs to address gaps in health care and advocating for practice and policy changes to improve the health care of childbearing women and infants. PMID- 20576077 TI - Social justice as a wider lens of support for childbearing women. AB - The ecological model is used as a framework for applying social justice concepts to the care of childbearing women and families. In this model, the environment of childbearing women has 3 distinct levels: macrosystem, mesosystem, and microsystem. Two scenarios are described and examples of nursing actions to promote social justice at each level are provided. This article demonstrates how maternal/infant nursing practice can be expanded to promote health equities, social justice, and support. PMID- 20576082 TI - The need for development of methodologies and methods. PMID- 20576078 TI - Social justice considerations in neonatal care for nurse managers and executives. AB - This article presents the struggle between social justice and market justice within the current health care system, specifically issues affecting neonatal care. Community benefit is described and discussed as an aspect of social justice demonstrated by hospitals. The federal and state Children's Health Insurance Program also is discussed in relation to social justice and health care costs. Implications for managers and executives overseeing neonatal care are presented in relation to the economic and social issues. PMID- 20576083 TI - Children's experiences of attitudes and rules for going to the toilet in school. AB - INTRODUCTION: School children often base their toilet habits on behavioural and social reasons. Bladder emptying problems, urinary tract infections and constipation are common health problems which are also associated with irregular toilet habits. School rules for going to the toilet have been shown to create difficulties for school children with bladder dysfunction. Aim of this study was to describe children's experiences of school rules for going to the toilet and their significance for the children. METHODS: Individual open-ended questions with 19 schoolchildren aged 9-16 in elementary schools. RESULTS: To manage the children's toilet needs, teachers used rules designed for maintaining order in the classroom. The children saw their toilets needs as a private matter and experienced it complicated to go to the toilet during recess as time was short and the risk for violation of their integrity was at its highest. The most frustrating when to comply with rules during lessons was to be forced to, in front of all their classmates, make public the need to go to the toilet: i.e the most private was exposed to the disclosure. CONCLUSION: The rules for going to the toilet came from the teachers' need for maintaining order in the classroom and were not adapted to the children's physical and developmental needs. To violate the integrity of children can affect their willingness to go to the school toilet which in turn affects their wellbeing during school time. PMID- 20576085 TI - Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study. AB - BACKGROUND: The use of honey as a natural product of Apis spp. for burn treatment has been widely applied for centuries. Tualang honey has been reported to have antibacterial properties against various microorganisms, including those from burn-related diagnoses, and is cheaper and easier to be absorbed by Aquacel dressing. The aim of this study is to evaluate the potential antibacterial properties of tualang honey dressing and to determine its effectiveness as a partial thickness burn wound dressing. METHODS: In order to quantitate the bioburden of the swabs, pour plates were performed to obtain the colony count (CFU/ml). Swabs obtained from burn wounds were streaked on blood agar and MacConkey agar for bacterial isolation and identification. Later, antibacterial activity of Aquacel-tualang honey, Aquacel-Manuka honey, Aquacel-Ag and Aquacel- plain dressings against bacteria isolated from patients were tested (in-vitro) to see the effectiveness of those dressings by zone of inhibition assays. RESULTS: Seven organisms were isolated. Four types of Gram-negative bacteria, namely Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas spp. and Acinetobacter spp., and three Gram-positive bacteria, namely Staphylococcus aureus, coagulase negative Staphylococcus aureus (CONS) and Streptococcus spp., were isolated. Total bacterial count decreased on day 6 and onwards. In the in-vitro antibacterial study, Aquacel-Ag and Aquacel-Manuka honey dressings gave better zone of inhibition for Gram positive bacteria compared to Aquacel-Tualang honey dressing. However, comparable results were obtained against Gram negative bacteria tested with Aquacel-Manuka honey and Aquacel-Tualang honey dressing. CONCLUSIONS: Tualang honey has a bactericidal as well as bacteriostatic effect. It is useful as a dressing, as it is easier to apply and is less sticky compared to Manuka honey. However, for Gram positive bacteria, tualang honey is not as effective as usual care products such as silver-based dressing or medical grade honey dressing. PMID- 20576086 TI - Validation of the historical adulthood physical activity questionnaire (HAPAQ) against objective measurements of physical activity. AB - BACKGROUND: Lifetime physical activity energy expenditure (PAEE) is an important determinant of risk for many chronic diseases but remains challenging to measure. Previously reported historical physical activity (PA) questionnaires appear to be reliable, but their validity is less well established. METHODS: We sought to design and validate an historical adulthood PA questionnaire (HAPAQ) against objective PA measurements from the same individuals. We recruited from a population-based cohort in Cambridgeshire, UK, (Medical Research Council Ely Study) in whom PA measurements, using individually calibrated heart rate monitoring, had been obtained in the past, once between 1994 and 1996 and once between 2000 and 2002. 100 individuals from this cohort attended for interview. Historical PA within the domains of home, work, transport, sport and exercise was recalled using the questionnaire by asking closed questions repeated for several discrete time periods from the age of 20 years old to their current age. The average PAEE from the 2 periods of objective measurements was compared to the self-reported data from the corresponding time periods in the questionnaire. RESULTS: Significant correlations were observed between HAPAQ-derived and objectively measured total PAEE for both time periods (Spearman r = 0.44; P < 0.001). Similarly, self-reported time spent in vigorous PA was significantly correlated with objective measurements of vigorous PA (Spearman r = 0.40; P < 0.001). CONCLUSIONS: HAPAQ demonstrates convergent validity for total PAEE and vigorous PA. This instrument will be useful for ranking individuals according to their past PA in studies of chronic disease aetiology, where activity may be an important underlying factor contributing to disease pathogenesis. PMID- 20576087 TI - Study of the nitric oxide system in the rat cerebellum during aging. AB - BACKGROUND: The cerebellum is the neural structure with the highest levels of nitric oxide, a neurotransmitter that has been proposed to play a key role in the brain aging, although knowledge concerning its contribution to cerebellar senescence is still unclear, due mainly to absence of integrative studies that jointly evaluate the main factors involved in its cell production and function. Consequently, in the present study, we investigate the expression, location, and activity of nitric oxide synthase isoenzymes; the protein nitration; and the production of nitric oxide in the cerebellum of adult and old rats. RESULTS: Our results show no variation in the expression of nitric oxide synthase isoforms with aging, although, we have detected some changes in the cellular distribution pattern of the inducible isoform particularly in the cerebellar nuclei. There is also an increase in nitric oxide synthase activity, as well as greater protein nitration levels, and maintenance of nitrogen oxides (NOx) levels in the senescent cerebellum. CONCLUSIONS: The nitric oxide/nitric oxide synthases system suffers from a number of changes, mainly in the inducible nitric oxide synthase distribution and in overall nitric oxide synthases activity in the senescent cerebellum, which result in an increase of the protein nitration. These changes might be related to the oxidative damage detected with aging in the cerebellum. PMID- 20576089 TI - Media response to colon cancer campaigns in Switzerland 2005-2007: regional newspapers are the most reliable among the printed media. AB - BACKGROUND: Health campaigns are frequently covered by printed media, but coverage is not homogeneous across different types of newspapers. Switzerland as a multilinguistic country with many newspapers offers a good field for study. A better understanding of how printed media report on national campaigns against colon cancer in the three main linguistic regions may help to improve future public health interventions. Therefore, we analyzed articles published between 2005 and 2007 during the campaigns "Darmkrebs-nie?" and "Self-Care" in the German, French and Italian regions of Switzerland. FINDINGS: Some 65% of articles reporting on colon cancer were in German, 23% and 12% were in French and Italian respectively. During the campaign, topics linked to colon cancer were increasingly covered by the media. Regional newspapers (66%) reported significantly more about colon cancer and produced the most detailed articles.Both gain- and loss-framed messages have been used by journalists, whereas the campaigns used merely gain-framed messages. Latin (French and Italian) newspapers mixed gain- and loss-framed messages in the same articles, while German articles mainly used a single frame throughout. CONCLUSIONS: Swiss German papers reported more about the topic and the reporting was quantitatively and qualitatively more prominent in regional papers. The press followed the campaigns closely only during the period of campaigning, with high coverage. We propose to consider the regional press as an important vehicle of health information. Moreover, slight differences in framing can be observed between German and Latin articles. PMID- 20576090 TI - Testis transcriptome analysis in male infertility: new insight on the pathogenesis of oligo-azoospermia in cases with and without AZFc microdeletion. AB - BACKGROUND: About 10% of cases of male infertility are due to the presence of microdeletions within the long arm of the Y chromosome (Yq). Despite the large literature covering this critical issue, very little is known about the pathogenic mechanism leading to spermatogenesis disruption in patients carrying these microdeletions. In order to identify the presence of specific molecular pathways leading to spermatogenic damage, testicular gene expression profiling was carried out by employing a microarray assay in 16 patients carrying an AZFc microdeletion or affected by idiopathic infertility. Hierarchical clustering was performed pooling the data set from 26 experiments (16 patients, 10 replicates). RESULTS: An intriguing and unexpected finding is that all the samples showing the AZFc deletion cluster together irrespectively of their testicular phenotypes. This cluster, including also four patients affected by idiopathic infertility, showed a downregulation of several genes related to spermatogenesis that are mainly involved in testicular mRNA storage. Interestingly, the four idiopathic patients present in the cluster showed no testicular expression of DAZ despite the absence of AZFc deletion in the peripheral blood. CONCLUSIONS: Our expression profiles analysis indicates that several forms of infertility can be triggered by a common pathogenic mechanism that is likely related to alterations in testicular mRNA storage. Our data suggest that a lack of testicular DAZ gene expression may be the trigger of such mechanism. Furthermore, the presence of AZFc deletions in mosaic or the loss of function of AZFc genes in absence of Yq deletion can perhaps explain these findings. Finally, based on our data, it is intriguing to hypothesize that DAZ gene dysfunctions can account for a larger number of previously thought "idiopathic" infertility cases and investigation of such testicular gene dysfunction can be important to reveal the molecular determinant of infertility than are undetected when only testing Yq deletions in peripheral blood. PMID- 20576088 TI - RNA interference (RNAi) screening approach identifies agents that enhance paclitaxel activity in breast cancer cells. AB - INTRODUCTION: Paclitaxel is a widely used drug in the treatment of patients with locally advanced and metastatic breast cancer. However, only a small portion of patients have a complete response to paclitaxel-based chemotherapy, and many patients are resistant. Strategies that increase sensitivity and limit resistance to paclitaxel would be of clinical use, especially for patients with triple negative breast cancer (TNBC). METHODS: We generated a gene set from overlay of the druggable genome and a collection of genomically deregulated gene transcripts in breast cancer. We used loss-of-function RNA interference (RNAi) to identify gene products in this set that, when targeted, increase paclitaxel sensitivity. Pharmacological agents that targeted the top scoring hits/genes from our RNAi screens were used in combination with paclitaxel, and the effects on the growth of various breast cancer cell lines were determined. RESULTS: RNAi screens performed herein were validated by identification of genes in pathways that, when previously targeted, enhanced paclitaxel sensitivity in the pre-clinical and clinical settings. When chemical inhibitors, CCT007093 and mithramycin, against two top hits in our screen, PPMID and SP1, respectively, were used in combination with paclitaxel, we observed synergistic growth inhibition in both 2D and 3D breast cancer cell cultures. The transforming growth factor beta (TGFbeta) receptor inhibitor, LY2109761, that targets the signaling pathway of another top scoring hit, TGFbeta1, was synergistic with paclitaxel when used in combination on select breast cancer cell lines grown in 3D culture. We also determined the relative paclitaxel sensitivity of 22 TNBC cell lines and identified 18 drug sensitive and four drug-resistant cell lines. Of significance, we found that both CCT007093 and mithramycin, when used in combination with paclitaxel, resulted in synergistic inhibition of the four paclitaxel-resistant TNBC cell lines. CONCLUSIONS: RNAi screening can identify druggable targets and novel drug combinations that can sensitize breast cancer cells to paclitaxel. This genomic based approach can be applied to a multitude of tumor-derived cell lines and drug treatments to generate requisite pre-clinical data for new drug combination therapies to pursue in clinical investigations. PMID- 20576091 TI - Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. AB - BACKGROUND: Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace environment. METHODS: After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2 week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms. RESULTS: Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX. CONCLUSIONS: LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1. PMID- 20576092 TI - Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial. AB - INTRODUCTION: Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years. RESULTS: Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P=0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years. CONCLUSIONS: Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18445519. PMID- 20576093 TI - Vascular health, diabetes, APOE and dementia: the Aging, Demographics, and Memory Study. AB - INTRODUCTION: Evidence from clinical samples and geographically limited population studies suggests that vascular health, diabetes and apolipoprotein epsilon4 (APOE) are associated with dementia. METHODS: A population-based sample of 856 individuals aged 71 years or older from all contiguous regions of the United States received an extensive in-home clinical and neuropsychological assessment in 2001-2003. The relation of hypertension, diabetes, heart disease, stroke, medication usage, and APOE epsilon4 to dementia was modelled using adjusted multivariable logistic regression. RESULTS: Treated stroke (odds ratio [OR] 3.8, 95% confidence interval [CI] 2.0, 7.2), untreated stroke (OR 3.5, 95% CI 1.7, 7.3), and APOE epsilon4 (OR 2.8, 95% CI 1.7, 4.5) all increased the odds of dementia. Treated hypertension was associated with lower odds of dementia (OR 0.5, 95% CI 0.3, 1.0). Diabetes and heart disease were not significantly associated with dementia. A significant interaction was observed between APOE epsilon4 and stroke (P = 0.001). CONCLUSIONS: Data from the first dementia study that is representative of the United States population suggest that stroke, the APOE epsilon4 allele and their interaction are strongly associated with dementia. PMID- 20576094 TI - Bistability in the actin cortex. AB - Multi-color fluorescence imaging experiments of wave forming Dictyostelium cells have revealed that actin waves separate two domains of the cell cortex that differ in their actin structure and phosphoinositide composition. We propose a bistable model of actin dynamics to account for these experimental observation. The model is based on the simplifying assumption that the actin cytoskeleton is composed of two distinct network types, a dendritic and a bundled network. The two structurally different states that were observed in experiments correspond to the stable fixed points in the bistable regime of this model. Each fixed point is dominated by one of the two network types. The experimentally observed actin waves can be considered as trigger waves that propagate transitions between the two stable fixed points.PACS Codes: 87.16.Ln, 87.17.Aa, 89.75.Fb. PMID- 20576095 TI - Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. AB - INTRODUCTION: Breast cancer is a profoundly heterogeneous disease with respect to biologic and clinical behavior. Gene-expression profiling has been used to dissect this complexity and to stratify tumors into intrinsic gene-expression subtypes, associated with distinct biology, patient outcome, and genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. METHODS: We applied global DNA copy number and gene-expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene-expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy-number aberrations and genomic subgroups of breast cancer. RESULTS: We identified 31 genomic regions that were highly amplified in > 1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions revealed six genomic subtypes, termed 17q12, basal-complex, luminal-simple, luminal-complex, amplifier, and mixed subtypes. Four of them had striking similarity to intrinsic gene-expression subtypes and showed associations to conventional tumor biomarkers and clinical outcome. However, luminal A classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having a better prognosis, whereas the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2 amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene-expression subtypes, the former being enriched for 8p12-amplified cases, whereas the mixed subtype included many tumors with predominantly DNA copy-number losses and poor prognosis. CONCLUSIONS: Global DNA copy-number analysis integrated with gene expression data can be used to dissect the complexity of breast cancer. This revealed six genomic subtypes with different clinical behavior and a striking concordance to the intrinsic subtypes. These genomic subtypes may prove useful for understanding the mechanisms of tumor development and for prognostic and treatment prediction purposes. PMID- 20576096 TI - A novel chemiluminescence assay of organophosphorous pesticide quinalphos residue in vegetable with luminol detection. AB - BACKGROUND: Organophosphorous pesticides are the most popular pesticides used in agriculture. As acetylcholinesterase inhibitors, organophosphorous pesticides are toxic organic chemicals. The control and detection of organophosphorous pesticide residue in food, water, and environment therefore plays a very important role in maintaining physical health. A sensitive, rapid, simple chemiluminescence(CL) method has been developed for the determination of quinalphos based on the reaction of quinalphos with luminol-H2O2 in an alkaline medium. The method has been applied to detection of quinalphos in vegetable samples with satisfactory results. RESULTS: The CL method for the determination of organophosphorous pesticide quinalphos is based on the phenomenon that quinalphos can apparently enhance the CL intensity of the luminol-H2O2 system. The optimal conditions were: luminol concentration 5.0 x 10-4 mol/L, H2O2 concentration 0.05 mol/L.pH value 13. In order to restrain the interference from metal ions, 1.0 x 10-3 mol/L of EDTA was added to the luminol solution. The possible mechanism was proposed. CONCLUSION: Under the optimum reaction conditions, CL was linear with the concentration of quinalphos in the range of 0.02 mug/mL -1.0 mug/mL and the detection limit was 0.0055 mug/mL (3sigma). This method has been successfully applied to the detection of quinalphos in vegetable samples. According to the experimental data, the average recoveries for quinalphos in cherry tomato and green pepper 97.20% and 90.13%. Meanwhile, the possible mechanism was proposed. PMID- 20576097 TI - The mitochondrial gene orfH79 plays a critical role in impairing both male gametophyte development and root growth in CMS-Honglian rice. AB - BACKGROUND: Cytoplasmic male sterility (CMS) has often been associated with abnormal mitochondrial open reading frames. The mitochondrial gene orfH79 is a candidate gene for causing the CMS trait in CMS-Honglian (CMS-HL) rice. However, whether the orfH79 expression can actually induce CMS in rice remains unclear. RESULTS: Western blot analysis revealed that the ORFH79 protein is mainly present in mitochondria of CMS-HL rice and is absent in the fertile line. To investigate the function of ORFH79 protein in mitochondria, this gene was fused to a mitochondrial transit peptide sequence and used to transform wild type rice, where its expression induced the gametophytic male sterile phenotype. In addition, excessive accumulation of reactive oxygen species (ROS) in the microspore, a reduced ATP/ADP ratio, decreased mitochondrial membrane potential and a lower respiration rate in the transgenic plants were found to be similar to those in CMS-HL rice. Moreover, retarded growth of primary and lateral roots accompanied by abnormal accumulation of ROS in the root tip was observed in both transgenic rice and CMS-HL rice (YTA). CONCLUSION: These results suggest that the expression of orfH79 in mitochondria impairs mitochondrial function, which affects the development of both male gametophytes and the roots of CMS-HL rice. PMID- 20576098 TI - An integrated web medicinal materials DNA database: MMDBD (Medicinal Materials DNA Barcode Database). AB - BACKGROUND: Thousands of plants and animals possess pharmacological properties and there is an increased interest in using these materials for therapy and health maintenance. Efficacies of the application is critically dependent on the use of genuine materials. For time to time, life-threatening poisoning is found because toxic adulterant or substitute is administered. DNA barcoding provides a definitive means of authentication and for conducting molecular systematics studies. Owing to the reduced cost in DNA authentication, the volume of the DNA barcodes produced for medicinal materials is on the rise and necessitates the development of an integrated DNA database. DESCRIPTION: We have developed an integrated DNA barcode multimedia information platform- Medicinal Materials DNA Barcode Database (MMDBD) for data retrieval and similarity search. MMDBD contains over 1000 species of medicinal materials listed in the Chinese Pharmacopoeia and American Herbal Pharmacopoeia. MMDBD also contains useful information of the medicinal material, including resources, adulterant information, medical parts, photographs, primers used for obtaining the barcodes and key references. MMDBD can be accessed at http://www.cuhk.edu.hk/icm/mmdbd.htm. CONCLUSIONS: This work provides a centralized medicinal materials DNA barcode database and bioinformatics tools for data storage, analysis and exchange for promoting the identification of medicinal materials. MMDBD has the largest collection of DNA barcodes of medicinal materials and is a useful resource for researchers in conservation, systematic study, forensic and herbal industry. PMID- 20576099 TI - Pulse pressure variation and volume responsiveness during acutely increased pulmonary artery pressure: an experimental study. AB - INTRODUCTION: We found that pulse pressure variation (PPV) did not predict volume responsiveness in patients with increased pulmonary artery pressure. This study tests the hypothesis that PPV does not predict fluid responsiveness during an endotoxin-induced acute increase in pulmonary artery pressure and right ventricular loading. METHODS: Pigs were subjected to endotoxemia (0.4 microg/kg/hour lipopolysaccharide), followed by volume expansion, subsequent hemorrhage (20% of estimated blood volume), retransfusion, and additional stepwise volume loading until cardiac output did not increase further (n = 5). A separate control group (n = 7) was subjected to bleeding, retransfusion, and volume expansion without endotoxemia. Systemic hemodynamics were measured at baseline and after each intervention, and PPV was calculated offline. Prediction of fluid-challenge-induced stroke volume increase by PPV was analyzed using receiver operating characteristic (ROC) curves. RESULTS: Sixty-eight volume challenges were performed in endotoxemic animals (22 before and 46 after hemorrhage), and 51 volume challenges in the controls. Endotoxin infusion resulted in an acute increase in pulmonary artery and central venous pressure and a decrease in stroke volume (all P < 0.05). In endotoxemia, 68% of volume challenges before hemorrhage increased the stroke volume by > 10%, but PPV did not predict fluid responsiveness (area under the ROC curve = 0.604, P = 0.461). After hemorrhage in endotoxemia, stroke volume increased in 48% and the predictive value of PPV improved (area under the ROC curve for PPV = 0.699, P = 0.021). In controls after hemorrhage, stroke volume increased in 67% of volume challenges and PPV was a predictor of fluid responsiveness (area under the ROC curve = 0.790, P = 0.001). CONCLUSIONS: Fluid responsiveness cannot be predicted with PPV during acute pulmonary hypertension in porcine endotoxemia. Even following severe hemorrhage during endotoxemia, the predictive value of PPV is marginal. PMID- 20576100 TI - "Does replication groups scoring reduce false positive rate in SNP interaction discovery? Response". AB - BACKGROUND: The genomewide evaluation of genetic epistasis is a computationally demanding task, and a current challenge in Genetics. HFCC (Hypothesis-Free Clinical Cloning) is one of the methods that have been suggested for genomewide epistasis analysis. In order to perform an exhaustive search of epistasis, HFCC has implemented several tools and data filters, such as the use of multiple replication groups, and direction of effect and control filters. A recent article has claimed that the use of multiple replication groups (as implemented in HFCC) does not reduce the false positive rate, and we hereby try to clarify these issues. RESULTS/DISCUSSION: HFCC uses, as an analysis strategy, the possibility of replicating findings in multiple replication groups, in order to select a liberal subset of preliminary results that are above a statistical criterion and consistent in direction of effect. We show that the use of replication groups and the direction filter reduces the false positive rate of a study, although at the expense of lowering the overall power of the study. A post-hoc analysis of these selected signals in the combined sample could then be performed to select the most promising results. CONCLUSION: Replication of results in independent samples is generally used in scientific studies to establish credibility in a finding. Nonetheless, the combined analysis of several datasets is known to be a preferable and more powerful strategy for the selection of top signals. HFCC is a flexible and complete analysis tool, and one of its analysis options combines these two strategies: a preliminary multiple replication group analysis to eliminate inconsistent false positive results, and a post-hoc combined-group analysis to select the top signals. PMID- 20576101 TI - Sequence and phylogenetic analysis of H7N3 avian influenza viruses isolated from poultry in Pakistan 1995-2004. AB - BACKGROUND: Avian influenza virus (AIV) infections have caused heavy economic losses to the poultry industry in Pakistan as well as numerous other regions worldwide. The first introduction of H7N3 AIV to Pakistan occurred during 1995, since then H7N3, H9N2 and H5N1 AIVs have each been sporadically isolated. This report evaluates the genetic origin of the H7N3 viruses from Pakistan collected 1995-2004 and how they disseminated within the country. To accomplish this we produced whole genome sequences for 6 H7N3 viruses and data for the HA and NA genes of an additional 7 isolates. All available sequence from H7N3 AIV from Pakistan was included in the analysis. RESULTS: Phylogenetic analysis revealed that there were two introductions of H7 into Pakistan and one N3 introduction. Only one of the H7 introductions appears to have become established in poultry in Pakistan, while the other was isolated from two separate outbreaks 6 years apart. The data also shows that reassortment has occurred between H7N3 and H9N2 viruses in the field, likely during co-infection of poultry. Also, with the exception of these few reassortant isolates, all 8 genes in the predominant H7N3 virus lineage have evolved to be phylogenetically distinct. CONCLUSIONS: Although rigorous control measures have been implemented in commercial poultry in Pakistan, AIV is sporadically transmitted to poultry and among the different poultry industry compartments (broilers, broiler breeders, table egg layers). Since there is one primary H7 lineage which persists and that has reassorted with the H9N2 AIV in poultry, it suggests that there is a reservoir with some link commercial poultry. On a general level, this offers insight into the molecular ecology of AIV in poultry where the virus has persisted despite vaccination and biosecurity. This data also illustrates the importance of sustained surveillance for AIVs in poultry. PMID- 20576102 TI - Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis. AB - BACKGROUND: The development of an effective vaccine against visceral leishmaniasis (VL) caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome associated L. donovani promastigote antigens (LAg) against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG) and Monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) with cationic liposomes, in combination with LAg, to confer protection against murine VL. RESULTS: All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-gamma and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-gamma but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-gamma and IL-4 response. Elicitation of moderate levels of prechallenge IFN-gamma along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. CONCLUSION: This comparative study reveals greater effectiveness of the liposomal vaccine for protection against progressive VL in BALB/c. Again, evaluation of the immune responses by vaccination emphasizes the need of stimulation of potent cellular immunity based on both Th1 and Th2 cell responses to confer protection against VL. PMID- 20576103 TI - Identification of viral infections in the prostate and evaluation of their association with cancer. AB - BACKGROUND: Several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses BKV, JCV, and SV40; human papillomaviruses (HPVs), and human cytomegalovirus (HCMV) infections. Recently, the Xenotropic Murine Leukemia Virus-related gammaretrovirus (XMRV) was identified in prostate tissue with a high prevalence observed in prostate cancer (PC) patients homozygous for the glutamine variant of the RNASEL protein (462Q/Q). Association studies with the R462Q allele and non-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. METHODS: 130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. RESULTS: R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. CONCLUSIONS: We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated. PMID- 20576104 TI - Mental health policy and development in Egypt - integrating mental health into health sector reforms 2001-9. AB - BACKGROUND: Following a situation appraisal in 2001, a six year mental health reform programme (Egymen) 2002-7 was initiated by an Egyptian-Finnish bilateral aid project at the request of a former Egyptian minister of health, and the work was incorporated directly into the Ministry of Health and Population from 2007 onwards. This paper describes the aims, methodology and implementation of the mental health reforms and mental health policy in Egypt 2002-2009. METHODS: A multi-faceted and comprehensive programme which combined situation appraisal to inform planning; establishment of a health sector system for coordination, supervision and training of each level (national, governorate, district and primary care); development workshops; production of toolkits, development of guidelines and standards; encouragement of intersectoral liaison at each level; integration of mental health into health management systems; and dedicated efforts to improve forensic services, rehabilitation services, and child psychiatry services. RESULTS: The project has achieved detailed situation appraisal, epidemiological needs assessment, inclusion of mental health into the health sector reform plans, and into the National Package of Essential Health Interventions, mental health masterplan (policy guidelines) to accompany the general health policy, updated Egyptian mental health legislation, Code of Practice, adaptation of the WHO primary care guidelines, primary care training, construction of a quality system of roles and responsibilities, availability of medicines at primary care level, public education about mental health, and a research programme to inform future developments. Intersectoral liaison with education, social welfare, police and prisons at national level is underway, but has not yet been established for governorate and district levels, nor mental health training for police, prison staff and teachers. CONCLUSIONS: The bilateral collaboration programme initiated a reform programme which has been sustained beyond the end of the funding. The project has demonstrated the importance of using a multi-faceted and comprehensive programme to promote sustainable system change, key elements of which include a focus on the use of rapid appropriate treatment at primary care level, strengthening the referral system, interministerial and intersectoral liaison, rehabilitation, and media work to mobilize community engagement. PMID- 20576105 TI - Calculation of partial isotope incorporation into peptides measured by mass spectrometry. AB - BACKGROUND: Stable isotope probing (SIP) technique was developed to link function, structure and activity of microbial cultures metabolizing carbon and nitrogen containing substrates to synthesize their biomass. Currently, available methods are restricted solely to the estimation of fully saturated heavy stable isotope incorporation and convenient methods with sufficient accuracy are still missing. However in order to track carbon fluxes in microbial communities new methods are required that allow the calculation of partial incorporation into biomolecules. RESULTS: In this study, we use the characteristics of the so-called 'half decimal place rule' (HDPR) in order to accurately calculate the partial13C incorporation in peptides from enzymatic digested proteins. Due to the clade crossing universality of proteins within bacteria, any available high-resolution mass spectrometry generated dataset consisting of tryptically-digested peptides can be used as reference.We used a freely available peptide mass dataset from Mycobacterium tuberculosis consisting of 315,579 entries. From this the error of estimated versus known heavy stable isotope incorporation from an increasing number of randomly drawn peptide sub-samples (100 times each; no repetition) was calculated. To acquire an estimated incorporation error of less than 5 atom %, about 100 peptide masses were needed. Finally, for testing the general applicability of our method, peptide masses of tryptically digested proteins from Pseudomonas putida ML2 grown on labeled substrate of various known concentrations were used and13C isotopic incorporation was successfully predicted. An easy-to use script 1 was further developed to guide users through the calculation procedure for their own data series. CONCLUSION: Our method is valuable for estimating13C incorporation into peptides/proteins accurately and with high sensitivity. Generally, our method holds promise for wider applications in qualitative and especially quantitative proteomics. PMID- 20576106 TI - Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis. AB - BACKGROUND: There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies. METHODOLOGY: A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA). RESULTS: Thirty six patients (mean age 59.8 +/- 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6%) with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50%) patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 +/- 1.6 vs 26.3 +/- 3.5 kg/m2, p < 0.0001; MAMC 19.4 +/- 1.5 vs 24.5 +/- 3.6 cm, p = 0.002) and females (BMI 19.4 +/- 2.7 vs 28.9 +/- 4.3, p = 0.001; MAMC 18.0 +/- 0.9 vs 28.1 +/- 3.6, p < 0.0001), but not with visceral proteins. The SGA demonstrated a trend towards more malnutrition in Child-Pugh C compared to Child Pugh B liver cirrhosis (40% grade C vs 25% grade C, p = 0.48). Alcoholic cirrhosis had a higher proportion of SGA grade C (41.7%) compared to viral (26.7%) and cryptogenic (28.6%) cirrhosis, but this was not statistically significant. CONCLUSION: Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis. PMID- 20576107 TI - Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1. AB - BACKGROUND: Human renal cell carcinoma (RCC) is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models. RESULTS: We here report a strong over-additive pro-apoptotic effect of ABT-737 and etoposide, vinblastine or paclitaxel but not 5-fluorouracil in cell lines from human RCC. ABT-737 showed very little activity as a single agent but killed RCC cells potently when anti apoptotic Mcl-1 or, unexpectedly, A1 was targeted by RNAi. This potent augmentation required endogenous Noxa protein since RNAi directed against Noxa but not against Bim or Puma reduced apoptosis induction by the combination of ABT 737 and etoposide or vinblastine. At the level of mitochondria, etoposide treatment had a similar sensitizing activity and allowed for ABT-737-induced release of cytochrome c. CONCLUSIONS: Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in RCC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC. Strikingly, A1 emerged in RCC cell lines as a protein of similar importance as the well-established Mcl-1 in protection against apoptosis in these cells. PMID- 20576108 TI - Helical tomotherapy for single and multiple liver tumours. AB - PURPOSE: Dosimetric evaluations of single and multiple liver tumours performed using intensity-modulated helical tomotherapy (HT) were quantitatively investigated. Step-and-shoot intensity-modulated radiotherapy (SaS-IMRT) was used as a benchmark. METHODS: Sixteen patients separated into two groups with primary hepatocellular carcinomas or metastatic liver tumours previously treated using SaS-IMRT were examined and re-planned by HT. The dosimetric indices used included the conformity index (CI) and homogeneity index (HI) for the planned target volume (PTV), max/mean dose, quality index (QI), normal tissue complication probability (NTCP), V(30 Gy), and V(50%) for the specified organs at risk (OARs). The monitor units per fraction (MU/fr) and delivery time were also analysed. RESULTS: For the single tumour group, both planning systems satisfied the required PTV prescription, but no statistical significance was shown by the indexes checking. A shorter delivery time and lower MU/fr value were achieved by the SaS-IMRT. For the group of multiple tumours, the average improvement in CI and HI was 14% and 4% for HT versus SaS-IMRT, respectively. Lower V(50%), V(30 Gy) and QI values were found, indicating a significant dosimetric gain in HT. The NTCP value of the normal liver was 20.27 +/- 13.29% for SaS-IMRT and 2.38 +/- 2.25% for HT, indicating fewer tissue complications following HT. The latter also required a shorter delivery time. CONCLUSIONS: Our study suggests dosimetric benefits of HT over SaS-IMRT plans in the case of multiple liver tumours, especially with regards sparing of OARs. No significant dosimetric difference was revealed in the case of single liver tumour, but SaS-IMRT showed better efficiency in terms of MU/fr and delivery time. PMID- 20576109 TI - Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease. AB - INTRODUCTION: Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease. METHODS: CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, beta-amyloid1 42 (Abeta42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants. RESULTS: AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP 1 levels compared to cognitively healthy individuals. In AD patients, the MMP 9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Abeta42 or the presence of the APOE epsilon4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels. CONCLUSIONS: This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction. PMID- 20576110 TI - Robustness from flexibility in the fungal circadian clock. AB - BACKGROUND: Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. RESULTS: The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq) gene inhibits its transcriptional activator white collar-1 (wc-1), interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on the circuit by the interlocking loop structure. CONCLUSIONS: Our model shows that the behaviour of the fungal clock in light-dark cycles can be accounted for by a transcription-translation feedback model of the central FRQ-WC oscillator. More generally, we provide an example of a biological circuit in which greater flexibility yields improved robustness, while also introducing novel sensitivity analysis techniques applicable to a broader range of cellular oscillators. PMID- 20576111 TI - Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Cote d'Ivoire. AB - BACKGROUND: In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women. METHODS: All HIV-infected women who initiated nevirapine-containing regimen in the MTCT Plus operational program in Abidjan, Cote d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs. RESULTS: From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm3 (IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm3 and women with a CD4 cell count 250 cells/mm3 at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs. CONCLUSION: CD4 cell count >250 cells/mm3 was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity. PMID- 20576112 TI - Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest. AB - BACKGROUND: Histone deacetylase inhibitors have been proposed as potential enhancers of the cytotoxic effect of cisplatin and other anticancer drugs. Their application would permit the use of lower therapeutic doses and reduction of the adverse side effects of the drugs. However, the molecular mechanisms by which they sensitize the cells towards anticancer drugs are not known in details, which is an obstacle in developing effective therapeutic protocols. RESULTS: In the present work, we studied the molecular mechanisms by which sodium butyrate sensitizes cancer cells towards cisplatin. HeLa cells were treated with 5 mM butyrate, with 8 microM cis-diaminedichloroplatinum II (cisplatin), or with both. Cells treated with both agents showed approximately two-fold increase of the mortality rate in comparison with cells treated with cisplatin only. Accordingly, the life span of albino mice transfected with Ehrlich ascites tumor was prolonged almost two-fold by treatment with cisplatin and butyrate in comparison with cisplatin alone. This showed that the observed synergism of cisplatin and butyrate was not limited to specific cell lines or in vitro protocols, but was also expressed in vivo during the process of tumor development. DNA labeling and fluorescence activated cell sorting experiments showed that cisplatin treatment inhibited DNA synthesis and arrested HeLa cells at the G1/S transition and early S phase of the cell cycle. Western blotting and chromatin immunoprecipitation revealed that this effect was accompanied with a decrease of histone H4 acetylation levels. Butyrate treatment initially reversed the effect of cisplatin by increasing the levels of histone H4 acetylation in euchromatin regions responsible for the G1/S phase transition and initiation of DNA synthesis. This abrogated the cisplatin imposed cell cycle arrest and the cells traversed S phase with damaged DNA. However, this effect was transient and continued only a few hours. The long-term effect of butyrate was a massive histone acetylation in both eu- and heterochromatin, inhibition of DNA replication and apoptosis. CONCLUSION: The study presents evidence that cell sensitization towards cisplatin by sodium butyrate is due to hyperacetylation of histone H4 in specific chromatin regions, which temporarily abrogates the cisplatin imposed cell cycle arrest. PMID- 20576113 TI - Remarkable features of ovarian morphology and reproductive hormones in insulin resistant Zucker fatty (fa/fa) rats. AB - BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats. PMID- 20576114 TI - WHO policy development processes for a new vaccine: case study of malaria vaccines. AB - BACKGROUND: Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. METHODS: The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. CASE DESCRIPTION: WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. DISCUSSION AND EVALUATION: Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. CONCLUSIONS: Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions. PMID- 20576115 TI - Coverage of Jade Goody's cervical cancer in UK newspapers: a missed opportunity for health promotion? AB - BACKGROUND: It has been claimed that publicity surrounding popular celebrity Jade Goody's experience of cervical cancer will raise awareness about the disease. This study examines the content of newspaper articles covering her illness to consider whether 'mobilising information' which could encourage women to adopt risk-reducing and health promoting behaviours has been included. METHODS: Content analysis of 15 national newspapers published between August 2008 and April 2009 FINDINGS: In the extensive coverage of Goody's illness (527 articles in the 7 months of study) few newspaper articles included information that might make women more aware of the signs and symptoms or risk factors for the disease, or discussed the role of the human papilloma virus (HPV) and the recently introduced HPV vaccination programme to reduce the future incidence of cervical cancer. For example, less than 5% of articles mentioned well-known risk-factors for cervical cancer and less than 8% gave any information about HPV. The 'human interest' aspects of Goody's illness (her treatment, the spread of her disease in later months, her wedding, and her preparations for her children's future) were more extensively covered. CONCLUSIONS: Newspaper coverage of Goody's illness has tended not to include factual or educational information that could mobilise or inform women, or help them to recognise early symptoms. However, the focus on personal tragedy may encourage women to be receptive to HPV vaccination or screening if her story acts as a reminder that cervical cancer can be a devastating and fatal disease in the longer term. PMID- 20576116 TI - Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community. AB - BACKGROUND: Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Rio Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. RESULTS: Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. CONCLUSIONS: Our results indicate that the acidophilic filaments are dynamic structures in which different mechanisms for biofilm formation/dispersion are operating. Specific transcriptomic fingerprints can be inferred for both planktonic and sessile cells, having the former a more active TCA cycle, while the mixed acid fermentation process dominate in the latter. The excretion of acetate may play a relevant ecological role as a source of electron donor for heterotrophic Fe3+ reducers like some Alphaproteobacteria, Acidobacterium spp. and Sulfobacillus spp., also present in the biofilm. Additionally, acetate may have a negative effect on bioleaching by inhibiting the growth of chemolithotrophic bacteria. PMID- 20576117 TI - The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis. AB - BACKGROUND: Arginine is an amino acid that serves as a substrate for the enzymes nitric oxide synthase (NOS) and arginase, leading to synthesis of NO and ornithine, respectively. As such, arginine has the potential to influence diverse fundamental processes in the lung. METHODS: We used mice deficient in cationic amino acid transporter (CAT) 2 in models of allergic airway inflammation and pulmonary fibrosis. RESULTS: We report that the arginine transport protein CAT2 was over-expressed in the lung during the induction of allergic airway inflammation. Furthermore, CAT2 mRNA was strongly induced by transgenically over expressed IL-4, and allergen-induced expression was dependent upon signal transducer-and-activator-of-transcription (STAT) 6. In situ mRNA hybridization demonstrated marked staining of CAT2, predominantly in scattered mononuclear cells. Analysis of allergic airway inflammation and bleomycin-induced inflammation in CAT2-deficient mice revealed that while inflammation was independent of CAT2 expression, bleomycin-induced fibrosis was dependent upon CAT2. Mechanistic analysis revealed that arginase activity in macrophages was partly dependent on CAT2. CONCLUSION: Taken together, these results identify CAT2 as a regulator of fibrotic responses in the lung. PMID- 20576118 TI - Poly(I:C) induces intense expression of c-IAP2 and cooperates with an IAP inhibitor in induction of apoptosis in cancer cells. AB - BACKGROUND: There is increasing evidence that the toll-like receptor 3 (TLR3) is an interesting target for anti-cancer therapy. Unfortunately, most laboratory investigations about the impact of TLR3 stimulation on human malignant cells have been performed with very high concentrations--5 to 100 microg/ml--of the prototype TLR3 ligand, poly(I:C). In a previous study focused on a specific type of human carcinoma - nasopharyngeal carcinoma - we have shown that concentrations of poly(I:C) as low as 100 ng/ml are sufficient to induce apoptosis of malignant cells when combined to a pharmacological antagonist of the IAP family based on Smac mimicry. METHODS: This observation prompted us to investigate the contribution of the IAP family in cell response to poly(I:C) in a variety of human malignant cell types. RESULTS: We report a rapid, intense and selective increase in c-IAP2 protein expression observed under stimulation by poly(I:C)(500 ng/ml) in all types of human malignant cells. In most cell types, this change in protein expression is underlain by an increase in c-IAP2 transcripts and dependent on the TLR3/TRIF pathway. When poly(I:C) is combined to the IAP inhibitor RMT 5265, a cooperative effect in apoptosis induction and/or inhibition of clonogenic growth is obtained in a large fraction of carcinoma and melanoma cell lines. CONCLUSIONS: Currently, IAP inhibitors like RMT 5265 and poly(I:C) are the subject of separate therapeutic trials. In light of our observations, combined use of both types of compounds should be considered for treatment of human malignancies including carcinomas and melanomas. PMID- 20576120 TI - Error, reproducibility and sensitivity: a pipeline for data processing of Agilent oligonucleotide expression arrays. AB - BACKGROUND: Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. RESULTS: We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that interarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log(2) units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. CONCLUSIONS: This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells. PMID- 20576121 TI - Cumulative exposure to air pollution and long term outcomes after first acute myocardial infarction: a population-based cohort study. Objectives and methodology. AB - BACKGROUND: Cardiovascular disease is a leading cause of morbidity and mortality worldwide and epidemiological studies have consistently shown an increased risk for cardiovascular events in relation to exposure to air pollution. The Israel Study of First Acute Myocardial Infarction was designed to longitudinally assess clinical outcomes, psychosocial adjustment and quality of life in patients hospitalized with myocardial infarction. The current study, by introducing retrospective air pollution data, will examine the association between exposure to air pollution and outcome in myocardial infarction survivors. This report will describe the methods implemented and measures employed. The study specifically aims to examine the relationship between residential exposure to air pollution and long-term risk of recurrent coronary event, heart failure, stroke, cardiac and all-cause death in a geographically defined cohort of patients with myocardial infarction. METHODS/DESIGN: All 1521 patients aged < or =65 years, admitted with first myocardial infarction between February 1992 and February 1993 to the 8 hospitals serving the population of central Israel, were followed for a median of 13 years. Data were collected on sociodemographic, clinical and environmental factors. Data from air quality monitoring stations will be incorporated retrospectively. Daily measures of air pollution will be summarised, allowing detailed maps to be developed in order to reflect chronic exposure for each participant. DISCUSSION: This study addresses some of the gaps in understanding of the prognostic importance of air pollution exposure after myocardial infarction, by allowing a sufficient follow-up period, using a well defined community cohort, adequately controlling for multiple and multilevel confounding factors and providing extensive data on various outcomes. PMID- 20576123 TI - The delivery of stop smoking support to people with mental health conditions: a survey of NHS stop smoking services. AB - BACKGROUND: People with mental health problems exhibit smoking rates up to three times that of the general population. Metabolic interactions between hydrocarbon agents in tobacco smoke and some antipsychotic drugs account for a change in medication metabolism on stopping smoking, and potentially for increased blood levels. Nicotine withdrawal can mimic or exacerbate symptoms of mental illness. Therefore, appropriate screening for mental health problems and liaison with local mental health care providers should be a priority for NHS Stop Smoking Services. The present study aimed to examine this issue through surveys with NHS Stop Smoking Service staff in London. METHODS: Semi-structured telephone interviews were conducted with one senior staff member from 27 of the 29 NHS Stop Smoking Services in London. RESULTS: It was found that only a minority of services routinely check the mental health status or mental health service use of their clients. In addition, most services do not routinely implement special checks or actions when mental health problems are revealed. It was notable that respondents reported a lack of strategic drivers supporting work with mental health patients (such as targets relating to successful quits) as well as a low level of partnership working with local mental health care providers. CONCLUSIONS: NHS Stop Smoking Services may not be operating appropriate procedures for supporting people with mental health problems. There is a need for local protocols to be implemented that include routine screening for mental health issues and liaison with mental health care providers. PMID- 20576122 TI - Complex life forms may arise from electrical processes. AB - There is still not an appealing and testable model to explain how single-celled organisms, usually following fusion of male and female gametes, proceed to grow and evolve into multi-cellular, complexly differentiated systems, a particular species following virtually an invariant and unique growth pattern. An intrinsic electrical oscillator, resembling the cardiac pacemaker, may explain the process. Highly auto-correlated, it could live independently of ordinary thermodynamic processes which mandate increasing disorder, and could coordinate growth and differentiation of organ anlage. PMID- 20576125 TI - Medical student attitudes toward video games and related new media technologies in medical education. AB - BACKGROUND: Studies in K-12 and college students show that their learning preferences have been strongly shaped by new media technologies like video games, virtual reality environments, the Internet, and social networks. However, there is no known research on medical students' game experiences or attitudes towards new media technologies in medical education. This investigation seeks to elucidate medical student experiences and attitudes, to see whether they warrant the development of new media teaching methods in medicine. METHODS: Medical students from two American universities participated. An anonymous, 30-item, cross-sectional survey addressed demographics, game play experience and attitudes on using new media technologies in medical education. Statistical analysis identified: 1) demographic characteristics; 2) differences between the two universities; 3) how video game play differs across gender, age, degree program and familiarity with computers; and 4) characteristics of students who play most frequently. RESULTS: 217 medical students participated. About half were female (53%). Respondents liked the idea of using technology to enhance healthcare education (98%), felt that education should make better use of new media technologies (96%), and believed that video games can have educational value (80%). A majority (77%) would use a multiplayer online healthcare simulation on their own time, provided that it helped them to accomplish an important goal. Men and women agreed that they were most inclined to use multiplayer simulations if they were fun (97%), and if they helped to develop skill in patient interactions (90%). However, there was significant gender dissonance over types of favorite games, the educational value of video games, and the desire to participate in games that realistically replicated the experience of clinical practice. CONCLUSIONS: Overall, medical student respondents, including many who do not play video games, held highly favorable views about the use of video games and related new media technology in medical education. Significant gender differences in game play experience and attitudes may represent male video game design bias that stresses male cognitive aptitudes; medical educators hoping to create serious games that will appeal to both men and women must avoid this. PMID- 20576124 TI - Mast cell repopulation of the peritoneal cavity: contribution of mast cell progenitors versus bone marrow derived committed mast cell precursors. AB - BACKGROUND: Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats. RESULTS: Two mast cell specific antibodies, mAb AA4 and mAb BGD6, were used to distinguish the committed mast cell precursor from more mature mast cells. The peritoneal cavity was depleted of mast cells using distilled water. Twelve hours after distilled water injection, very immature mast cells could be isolated from the blood and by 48 hours were present in the peritoneal cavity. At this same time the percentage of mast cells in mitosis increased fourfold. Mast cell depletion of the peritoneal cavity also reduced the total number of mast cells in the bone marrow, but increased the number of mast cell committed precursors. CONCLUSIONS: In response to mast cell depletion of the peritoneal cavity, a mast cell progenitor is released into the circulation and participates in repopulation of the peritoneal cavity, while the committed mast cell precursor is retained in the bone marrow. PMID- 20576126 TI - Application of a target array comparative genomic hybridization to prenatal diagnosis. AB - BACKGROUND: While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies. METHODS: We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping. RESULTS: In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis. CONCLUSIONS: We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically uncertain genomic regions. PMID- 20576127 TI - Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis. AB - BACKGROUND: Left ventricular (LV) hypertrophy is common among patients on hemodialysis. While a relationship between blood pressure (BP) and LV hypertrophy has been established, it is unclear which BP measurement method is the strongest correlate of LV hypertrophy. We sought to determine agreement between various blood pressure measurement methods, as well as identify which method was the strongest correlate of LV hypertrophy among patients on hemodialysis. METHODS: This was a post-hoc analysis of data from a randomized controlled trial. We evaluated the agreement between seven BP measurement methods: standardized measurement at baseline; single pre- and post-dialysis, as well as mean intra dialytic measurement at baseline; and cumulative pre-, intra- and post-dialysis readings (an average of 12 monthly readings based on a single day per month). Agreement was assessed using Lin's concordance correlation coefficient (CCC) and the Bland Altman method. Association between BP measurement method and LV hypertrophy on baseline cardiac MRI was determined using receiver operating characteristic curves and area under the curve (AUC). RESULTS: Agreement between BP measurement methods in the 39 patients on hemodialysis varied considerably, from a CCC of 0.35 to 0.94, with overlapping 95% confidence intervals. Pre dialysis measurements were the weakest predictors of LV hypertrophy while standardized, post- and inter-dialytic measurements had similar and strong (AUC 0.79 to 0.80) predictive power for LV hypertrophy. CONCLUSIONS: A single standardized BP has strong predictive power for LV hypertrophy and performs just as well as more resource intensive cumulative measurements, whereas pre-dialysis blood pressure measurements have the weakest predictive power for LV hypertrophy. Current guidelines, which recommend using pre-dialysis measurements, should be revisited to confirm these results. PMID- 20576129 TI - Isolation of deoxynivalenol-transforming bacteria from the chicken intestines using the approach of PCR-DGGE guided microbial selection. AB - BACKGROUND: Contamination of grains with trichothecene mycotoxins, especially deoxynivalenol (DON), has been an ongoing problem for Canada and many other countries. Mycotoxin contamination creates food safety risks, reduces grain market values, threatens livestock industries, and limits agricultural produce exports. DON is a secondary metabolite produced by some Fusarium species of fungi. To date, there is a lack of effective and economical methods to significantly reduce the levels of trichothecene mycotoxins in food and feed, including the efforts to breed Fusarium pathogen-resistant crops and chemical/physical treatments to remove the mycotoxins. Biological approaches, such as the use of microorganisms to convert the toxins to non- or less toxic compounds, have become a preferred choice recently due to their high specificity, efficacy, and environmental soundness. However, such approaches are often limited by the availability of microbial agents with the ability to detoxify the mycotoxins. In the present study, an approach with PCR-DGGE guided microbial selection was developed and used to isolate DON -transforming bacteria from chicken intestines, which resulted in the successful isolation of several bacterial isolates that demonstrated the function to transform DON to its de epoxy form, deepoxy-4-deoxynivalenol (DOM-1), a product much less toxic than DON. RESULTS: The use of conventional microbiological selection strategies guided by PCR-DGGE (denaturing gradient gel electrophoresis) bacterial profiles for isolating DON-transforming bacteria has significantly increased the efficiency of the bacterial selection. Ten isolates were identified and isolated from chicken intestines. They were all able to transform DON to DOM-1. Most isolates were potent in transforming DON and the activity was stable during subculturing. Sequence data of partial 16S rRNA genes indicate that the ten isolates belong to four different bacterial groups, Clostridiales, Anaerofilum, Collinsella, and Bacillus. CONCLUSIONS: The approach with PCR-DGGE guided microbial selection was effective in isolating DON-transforming bacteria and the obtained bacterial isolates were able to transform DON. PMID- 20576128 TI - Bicyclic triterpenoid Iripallidal induces apoptosis and inhibits Akt/mTOR pathway in glioma cells. AB - BACKGROUND: The highly resistant nature of glioblastoma multiforme (GBM) to chemotherapy prompted us to evaluate the efficacy of bicyclic triterpenoid Iripallidal against GBM in vitro. METHODS: The effect of Iripallidal on proliferation and apoptosis in glioma cell lines was evaluated by MTS, colony formation and caspase-3 activity. The effect of iripallidal to regulate (i) Akt/mTOR and STAT3 signaling (ii) molecules associated with cell cycle and DNA damage was evaluated by Western blot analysis. The effect of Iripallidal on telomerase activity was also determined. RESULTS: Iripallidal (i) induced apoptosis, (ii) inhibited Akt/mTOR and STAT3 signaling, (iii) altered molecules associated with cell cycle and DNA damage, (iv) inhibited telomerase activity and colony forming efficiency of glioma cells. In addition, Iripallidal displayed anti-proliferative activity against non-glioma cancer cell lines of diverse origin. CONCLUSION: The ability of Iripallidal to serve as a dual-inhibitor of Akt/mTOR and STAT3 signaling warrants further investigation into its role as a therapeutic strategy against GBM. PMID- 20576130 TI - Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium. AB - OBJECTIVES: It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The major objective of this study was to explore and determine whether platelet activating factor (PAF) and receptor associated networking pathways might significantly induce malignant potential in BRCA1-mutant at-risk epithelial cells. METHODS: BRCA1-mutant ovarian epithelial cell lines including (HOSE-636, HOSE-642), BRCA1-mutant ovarian cancer cell (UWB1.289), wild type normal ovarian epithelial cell (HOSE-E6E7) and cancerous cell line (OVCA429), and the non-malignant BRCA1-mutant distal fallopian tube (fimbria) tissue specimens were used in this study. Mutation analysis, kinase microarray, western blot, immune staining, co-immune precipitation, cell cycle, apoptosis, proliferation and bioinformatic pathway analysis were applied. RESULTS: We found that PAF, as a potent pro-inflammatory mediator, induced significant anti-apoptotic effect in BRCA1-mutant ovarian surface epithelial cells, but not in wild type HOSE cells. With kinase microarray technology and the specific immune approaches, we found that phosphor-STAT1 was activated by 100 nM PAF treatment only in BRCA1-mutant associated at-risk ovarian epithelial cells and ovarian cancer cells, but not in BRCA1-wild type normal (HOSE-E6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that elevated PAFR expression is associated with protein-protein interactions of PAFR-FAK and FAK-STAT1 in BRCA1-mutant ovarian epithelial cells, but not in the wild-type control cells. CONCLUSION: Previous studies showed that potent inflammatory lipid mediators such as PAF and its receptor (PAFR) significantly contribute to cancer progression and metastasis. Our findings suggest that these potent inflammatory lipids and receptor pathways are significantly involved in the early malignant transformation through PAFR-FAK-STAT1 networking and to block apoptosis pathway in BRCA1 dysfunctional at-risk ovarian epithelium. PMID- 20576131 TI - Applying an extended theoretical framework for data collection mode to health services research. AB - BACKGROUND: Over the last 30 years options for collecting self-reported data in health surveys and questionnaires have increased with technological advances. However, mode of data collection such as face-to-face interview or telephone interview can affect how individuals respond to questionnaires. This paper adapts a framework for understanding mode effects on response quality and applies it to a health research context. DISCUSSION: Data collection modes are distinguished by key features (whether the survey is self- or interviewer-administered, whether or not it is conducted by telephone, whether or not it is computerised, whether it is presented visually or aurally). Psychological appraisal of the survey request will initially entail factors such as the cognitive burden upon the respondent as well as more general considerations about participation. Subsequent psychological response processes will further determine how features of the data collection mode impact upon the quality of response provided. Additional antecedent factors which may further interact with the response generation process are also discussed. These include features of the construct being measured such as sensitivity, and of the respondent themselves (e.g. their socio-demographic characteristics). How features of this framework relate to health research is illustrated by example. SUMMARY: Mode features can affect response quality. Much existing evidence has a broad social sciences research base but is of importance to health research. Approaches to managing mode feature effects are discussed. Greater consideration must be given to how features of different data collection approaches affect response from participants in studies. Study reports should better clarify such features rather than rely upon global descriptions of data collection mode. PMID- 20576132 TI - A phylogenetic survey of myotubularin genes of eukaryotes: distribution, protein structure, evolution, and gene expression. AB - BACKGROUND: Phosphorylated phosphatidylinositol (PtdIns) lipids, produced and modified by PtdIns kinases and phosphatases, are critical to the regulation of diverse cellular functions. The myotubularin PtdIns-phosphate phosphatases have been well characterized in yeast and especially animals, where multiple isoforms, both catalytically active and inactive, occur. Myotubularin mutations bring about disruption of cellular membrane trafficking, and in humans, disease. Previous studies have suggested that myotubularins are widely distributed amongst eukaryotes, but key evolutionary questions concerning the origin of different myotubularin isoforms remain unanswered, and little is known about the function of these proteins in most organisms. RESULTS: We have identified 80 myotubularin homologues amidst the completely sequenced genomes of 30 organisms spanning four eukaryotic supergroups. We have mapped domain architecture, and inferred evolutionary histories. We have documented an expansion in the Amoebozoa of a family of inactive myotubularins with a novel domain architecture, which we dub "IMLRK" (inactive myotubularin/LRR/ROCO/kinase). There is an especially large myotubularin gene family in the pathogen Entamoeba histolytica, the majority of them IMLRK proteins. We have analyzed published patterns of gene expression in this organism which indicate that myotubularins may be important to critical life cycle stage transitions and host infection. CONCLUSIONS: This study presents an overall framework of eukaryotic myotubularin gene evolution. Inactive myotubularin homologues with distinct domain architectures appear to have arisen on three separate occasions in different eukaryotic lineages. The large and distinctive set of myotubularin genes found in an important pathogen species suggest that in this organism myotubularins might present important new targets for basic research and perhaps novel therapeutic strategies. PMID- 20576133 TI - Different levels of overnutrition and weight gain during pregnancy have differential effects on fetal growth and organ development. AB - BACKGROUND: Nearly 50% of U.S. women of child-bearing age are overweight or obese, conditions linked to offspring obesity and diabetes. METHODS: Utilizing the sheep, females were fed a highly palatable diet at two levels of overfeeding designed to induce different levels of maternal body weight increase and adiposity at conception, and from conception to midgestation. Fetal growth and organ development were then evaluated at midgestation in response to these two different levels of overfeeding. Ewes were fed to achieve: 1) normal weight gain (control, C), 2) overweight (125% of National Research Council [NRC] recommendations, OW125) or 3) obesity (150% of NRC recommendations, OB150) beginning 10 wks prior to breeding and through midgestation. Body fat % and insulin sensitivity were assessed at three points during the study: 1) diet initiation, 2) conception and 3) mid-gestation. Ewes were necropsied and fetuses recovered at mid-gestation (day 78). RESULTS: OB150 ewes had a higher % body fat than OW125 ewes prior to breeding (P = 0.03), but not at mid-gestation (P = 0.37). Insulin sensitivity decreased from diet initiation to mid-gestation (P = 0.04), and acute insulin response to glucose tended to be greater in OB150 ewes than C ewes (P = 0.09) and was greater than in OW125 ewes (P = 0.02). Fetal crown rump length, thoracic and abdominal girths, and fetal perirenal fat were increased in the OW125 and OB150 versus C ewes at mid-gestation. However, only fetal heart, pancreas, and liver weights, as well as lipid content of fetal liver, were increased (P < 0.05) in OB150 ewes versus both C and OW125 ewes at midgestation. CONCLUSIONS: These data demonstrate that different levels of overfeeding, resulting in differing levels of maternal weight gain and adiposity prior to and during pregnancy, lead to differential effects on fetal overgrowth and organ development. PMID- 20576134 TI - The heparan sulfate co-receptor and the concentration of fibroblast growth factor 2 independently elicit different signalling patterns from the fibroblast growth factor receptor. AB - BACKGROUND: The fibroblast growth factor receptor (FGFR) interprets concentration gradients of FGF ligands and structural changes in the heparan sulfate (HS) co receptor to generate different cellular responses. However, whether the FGFR generates different signals is not known. RESULTS: We have previously shown in rat mammary fibroblasts that in cells deficient in sulfation, and so in HS co receptor, FGF-2 can only stimulate a transient phosphorylation of p42/44 MAPK and so cannot stimulate DNA synthesis. Here we demonstrate that this is because in the absence of HS, FGF-2 fails to stimulate the phosphorylation of the adaptor FGFR substrate 2 (FRS2). In cells possessing the HS co-receptor, FGF-2 elicits a bell-shaped dose response: optimal concentrations stimulate DNA synthesis, but supramaximal concentrations (>/= 100 ng/mL) have little effect. At optimal concentrations (300 pg/mL) FGF-2 stimulates a sustained dual phosphorylation of p42/44 MAPK and tyrosine phosphorylation of FRS2. In contrast, 100 ng/mL FGF-2 only stimulates a transient early peak of p42/44 MAPK phosphorylation and fails to stimulate appreciably the phosphorylation of FRS2 on tyrosine. CONCLUSIONS: These results suggest that the nature of the FGFR signal produced is determined by a combination of the HS co-receptor and the concentration of FGF ligand. Both the phosphorylation of the adaptor FRS2, the kinetics (sustained or transient) of phosphorylation of p42/44(MAPK) are varied, and so differing cellular responses are produced. PMID- 20576135 TI - Combination therapy in hypertension: An update. AB - Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females. PMID- 20576136 TI - SOPRA: Scaffolding algorithm for paired reads via statistical optimization. AB - BACKGROUND: High throughput sequencing (HTS) platforms produce gigabases of short read (<100 bp) data per run. While these short reads are adequate for resequencing applications, de novo assembly of moderate size genomes from such reads remains a significant challenge. These limitations could be partially overcome by utilizing mate pair technology, which provides pairs of short reads separated by a known distance along the genome. RESULTS: We have developed SOPRA, a tool designed to exploit the mate pair/paired-end information for assembly of short reads. The main focus of the algorithm is selecting a sufficiently large subset of simultaneously satisfiable mate pair constraints to achieve a balance between the size and the quality of the output scaffolds. Scaffold assembly is presented as an optimization problem for variables associated with vertices and with edges of the contig connectivity graph. Vertices of this graph are individual contigs with edges drawn between contigs connected by mate pairs. Similar graph problems have been invoked in the context of shotgun sequencing and scaffold building for previous generation of sequencing projects. However, given the error-prone nature of HTS data and the fundamental limitations from the shortness of the reads, the ad hoc greedy algorithms used in the earlier studies are likely to lead to poor quality results in the current context. SOPRA circumvents this problem by treating all the constraints on equal footing for solving the optimization problem, the solution itself indicating the problematic constraints (chimeric/repetitive contigs, etc.) to be removed. The process of solving and removing of constraints is iterated till one reaches a core set of consistent constraints. For SOLiD sequencer data, SOPRA uses a dynamic programming approach to robustly translate the color-space assembly to base space. For assessing the quality of an assembly, we report the no-match/mismatch error rate as well as the rates of various rearrangement errors. CONCLUSIONS: Applying SOPRA to real data from bacterial genomes, we were able to assemble contigs into scaffolds of significant length (N50 up to 200 Kb) with very few errors introduced in the process. In general, the methodology presented here will allow better scaffold assemblies of any type of mate pair sequencing data. PMID- 20576137 TI - Mental health first aid training for the Chinese community in Melbourne, Australia: effects on knowledge about and attitudes toward people with mental illness. AB - BACKGROUND: The aim of this study was to investigate in members of the Chinese community in Melbourne the impact of Mental Health First Aid (MHFA) training on knowledge about mental disorders and on attitudes to people with mental illness. The hypotheses were that at the end of the training participants would have increased knowledge of mental disorders and related treatments, and decreased negative attitudes towards people with mental disorders. METHODS: Respondents were 108 participants of three MHFA training workshops for the Chinese community in Melbourne conducted by a qualified MHFA trainer. Participants completed the research questionnaire prior to the commencement of the training (pre-test) and at its completion (post-test). The questionnaires assessed participants' ability to recognize a mental disorder (depression and schizophrenia) described in the vignettes, knowledge about the professional help and treatment, and negative attitudes towards people with mental illness. RESULTS: Between pre- and post-test there was significant improvement in the recognition of mental disorders, beliefs about treatment became more concordant with health professionals, and negative attitudes reduced. CONCLUSION: The MHFA training course for general members of the Chinese community in Melbourne produced significant positive change in the level of mental health literacy and reductions in stigmatizing attitudes. The evidence from this study, together with the accumulated evidence of the benefits of MHFA training in the general Australian community, suggests that this approach should be scaled up to a level where it can have an impact on the whole of the Chinese community in Australia. PMID- 20576139 TI - Examining smoking-induced differential gene expression changes in buccal mucosa. AB - BACKGROUND: Gene expression changes resulting from conditions such as disease, environmental stimuli, and drug use, can be monitored in the blood. However, a less invasive method of sample collection is of interest because of the discomfort and specialized personnel necessary for blood sampling especially if multiple samples are being collected. Buccal mucosa cells are easily collected and may be an alternative sample material for biomarker testing. A limited number of studies, primarily in the smoker/oral cancer literature, address this tissue's efficacy as an RNA source for expression analysis. The current study was undertaken to determine if total RNA isolated from buccal mucosa could be used as an alternative tissue source to assay relative gene expression. METHODS: Total RNA was isolated from swabs, reverse transcribed and amplified. The amplified cDNA was used in RT-qPCR and microarray analyses to evaluate gene expression in buccal cells. Initially, RT-qPCR was used to assess relative transcript levels of four genes from whole blood and buccal cells collected from the same seven individuals, concurrently. Second, buccal cell RNA was used for microarray-based differential gene expression studies by comparing gene expression between a group of female smokers and nonsmokers. RESULTS: An amplification protocol allowed use of less buccal cell total RNA (50 ng) than had been reported previously with human microarrays. Total RNA isolated from buccal cells was degraded but was of sufficient quality to be used with RT-qPCR to detect expression of specific genes. We report here the finding of a small number of statistically significant differentially expressed genes between smokers and nonsmokers, using buccal cells as starting material. Gene Set Enrichment Analysis confirmed that these genes had a similar expression pattern to results from another study. CONCLUSIONS: Our results suggest that despite a high degree of degradation, RNA from buccal cells from cheek mucosa could be used to detect differential gene expression between smokers and nonsmokers. However the RNA degradation, increase in sample variability and microarray failure rate show that buccal samples should be used with caution as source material in expression studies. PMID- 20576138 TI - Genome-wide identification and expression analysis of serine proteases and homologs in the silkworm Bombyx mori. AB - BACKGROUND: Serine proteases (SPs) and serine proteases homologs (SPHs) are a large group of proteolytic enzymes, with important roles in a variety of physiological processes, such as cell signalling, defense and development. Genome wide identification and expression analysis of serine proteases and their homologs in the silkworm might provide valuable information about their biological functions. RESULTS: In this study, 51 SP genes and 92 SPH genes were systematically identified in the genome of the silkworm Bombyx mori. Phylogenetic analysis indicated that six gene families have been amplified species specifically in the silkworm, and the members of them showed chromosomal distribution of tandem repeats. Microarray analysis suggests that many silkworm specific genes, such as members of SP_fam12, 13, 14 and 15, show expression patterns that are specific to tissues or developmental stages. The roles of SPs and SPHs in resisting pathogens were investigated in silkworms when they were infected by Escherichia coli, Bacillus bombysepticus, Batrytis bassiana and B. mori nucleopolyhedrovirus, respectively. Microarray experiment and real-time quantitative RT-PCR showed that 18 SP or SPH genes were significantly up regulated after pathogen induction, suggesting that SP and SPH genes might participate in pathogenic microorganism resistance in B. mori. CONCLUSION: Silkworm SP and SPH genes were identified. Comparative genomics showed that SP and SPH genes belong to a large family, whose members are generated mainly by tandem repeat evolution. We found that silkworm has species-specific SP and SPH genes. Phylogenetic and microarray analyses provide an overview of the silkworm SP and SPHs, and facilitate future functional studies on these enzymes. PMID- 20576140 TI - Predicting nucleosome positioning using a duration Hidden Markov Model. AB - BACKGROUND: The nucleosome is the fundamental packing unit of DNAs in eukaryotic cells. Its detailed positioning on the genome is closely related to chromosome functions. Increasing evidence has shown that genomic DNA sequence itself is highly predictive of nucleosome positioning genome-wide. Therefore a fast software tool for predicting nucleosome positioning can help understanding how a genome's nucleosome organization may facilitate genome function. RESULTS: We present a duration Hidden Markov model for nucleosome positioning prediction by explicitly modeling the linker DNA length. The nucleosome and linker models trained from yeast data are re-scaled when making predictions for other species to adjust for differences in base composition. A software tool named NuPoP is developed in three formats for free download. CONCLUSIONS: Simulation studies show that modeling the linker length distribution and utilizing a base composition re-scaling method both improve the prediction of nucleosome positioning regarding sensitivity and false discovery rate. NuPoP provides a user friendly software tool for predicting the nucleosome occupancy and the most probable nucleosome positioning map for genomic sequences of any size. When compared with two existing methods, NuPoP shows improved performance in sensitivity. PMID- 20576141 TI - Changing clinical needs of people living with AIDS and receiving home based care in Malawi--the Bangwe Home Based Care Project 2003-2008--a descriptive study. AB - BACKGROUND: Home based care (HBC) has been an important component of the response to the AIDS epidemic in Africa, and particularly so before antiretroviral therapy (ART) became available. Has HBC become unnecessary now that ART is available in many African countries? One way to investigate this is to assess the changing need for comprehensive HBC as an ART programme becomes available. The Bangwe HBC programme in Malawi has been collecting data since 2003 before ART became available in 2005/6. Has the introduction of ART changed the clinical needs for HBC? METHODS: Information obtained at initial assessment and follow up visits of patients receiving HBC were combined to assess case severity, survival and the response to treatment. This information was used to assess trends in mortality and the incidence, duration and severity of common symptoms over a six year period in a defined urban population in Malawi. RESULTS: 1266 patients, of whom 1190 were followed up and of whom 652 (55%) died, were studied. 282 (25%) patients died within two months of being first seen with an improvement between 2003-2005 and 2006-2008 of reduced mortality from 28% to 20%. 341 (27%) patients were unable to care for themselves on first assessment and 675 (53%) had stage 4 AIDS disease. Most patients had a mix of symptoms at presentation. Self care increased somewhat over the six years although case severity as measured by WHO staging and nutritional status did not.350 patients were on ART either started before or after initial assessment. There were significant barriers to accessing ART with 156 (51%) of 304 stage 3 or 4 patients first assessed in 2007 or 2008 not receiving ART.Over the six year period new HBC cases reduced by 8% and follow up visits increased by 9% a year. Between 4 and 5 people sought HBC for the first time each week from an urban health centre catchment of 100,000, which required 37.3 follow up visits each week. CONCLUSIONS: Since the availability of ART in the local health facilities and despite strenuous efforts to persuade people to seek HIV testing and ART, in practice barriers existed and half the eligible HBC patients did not have access to ART. This is one reason why the clinical need for HBC services had not changed much. In terms of quantity of care the number of new patients seeking HBC reduced by 8% a year. In terms of content of care, while there had been a marginal increase in self care the severity of illness had not changed and the survival of a significant proportion of patients generated the need for repeat visits, which increased by 9% a year. In conclusion, although the content has changed the need for HBC has not diminished despite the availability of ART. PMID- 20576142 TI - Light whole genome sequence for SNP discovery across domestic cat breeds. AB - BACKGROUND: The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus--FeLV, feline coronavirus--FECV, feline immunodeficiency virus--FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. DESCRIPTION: To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. CONCLUSIONS: These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases. PMID- 20576143 TI - Molecular analysis of type 3 fimbrial genes from Escherichia coli, Klebsiella and Citrobacter species. AB - BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in the United States and is caused by a range of uropathogens. Biofilm formation by uropathogens that cause CAUTI is often mediated by cell surface structures such as fimbriae. In this study, we characterised the genes encoding type 3 fimbriae from CAUTI strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri and Citrobacter freundii. RESULTS: Phylogenetic analysis of the type 3 fimbrial genes (mrkABCD) from 39 strains revealed they clustered into five distinct clades (A-E) ranging from one to twenty-three members. The majority of sequences grouped in clade A, which was represented by the mrk gene cluster from the genome sequenced K. pneumoniae MGH78578. The E. coli and K. pneumoniae mrkABCD gene sequences clustered together in two distinct clades, supporting previous evidence for the occurrence of inter-genera lateral gene transfer. All of the strains examined caused type 3 fimbriae mediated agglutination of tannic acid treated human erythrocytes despite sequence variation in the mrkD-encoding adhesin gene. Type 3 fimbriae deletion mutants were constructed in 13 representative strains and were used to demonstrate a direct role for type 3 fimbriae in biofilm formation. CONCLUSIONS: The expression of functional type 3 fimbriae is common to many Gram-negative pathogens that cause CAUTI and is strongly associated with biofilm growth. Our data provides additional evidence for the spread of type 3 fimbrial genes by lateral gene transfer. Further work is now required to substantiate the clade structure reported here by examining more strains as well as other bacterial genera that make type 3 fimbriae and cause CAUTI. PMID- 20576144 TI - Coordination of the maize transcriptome by a conserved circadian clock. AB - BACKGROUND: The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. RESULTS: Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. CONCLUSIONS: Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species. PMID- 20576145 TI - Bed net ownership in Kenya: the impact of 3.4 million free bed nets. AB - BACKGROUND: In July and September 2006, 3.4 million long-lasting insecticide treated bed nets (LLINs) were distributed free in a campaign targeting children 0 59 months old (CU5s) in the 46 districts with malaria in Kenya. A survey was conducted one month after the distribution to evaluate who received campaign LLINs, who owned insecticide-treated bed nets and other bed nets received through other channels, and how these nets were being used. The feasibility of a distribution strategy aimed at a high-risk target group to meet bed net ownership and usage targets is evaluated. METHODS: A stratified, two-stage cluster survey sampled districts and enumeration areas with probability proportional to size. Handheld computers (PDAs) with attached global positioning systems (GPS) were used to develop the sampling frame, guide interviewers back to chosen households, and collect survey data. RESULTS: In targeted areas, 67.5% (95% CI: 64.6, 70.3%) of all households with CU5s received campaign LLINs. Including previously owned nets, 74.4% (95% CI: 71.8, 77.0%) of all households with CU5s had an ITN. Over half of CU5s (51.7%, 95% CI: 48.8, 54.7%) slept under an ITN during the previous evening. Nearly forty percent (39.1%) of all households received a campaign net, elevating overall household ownership of ITNs to 50.7% (95% CI: 48.4, 52.9%). CONCLUSIONS: The campaign was successful in reaching the target population, families with CU5s, the risk group most vulnerable to malaria. Targeted distribution strategies will help Kenya approach indicator targets, but will need to be combined with other strategies to achieve desired population coverage levels. PMID- 20576146 TI - Larval trematode communities in Radix auricularia and Lymnaea stagnalis in a reservoir system of the Ruhr River. AB - BACKGROUND: Analysis of the data available from traditional faunistic approaches to mollusc-trematode systems covering large spatial and/or temporal scales in Europe convinced us that a parasite community approach in well-defined aquatic ecosystems is essential for the substantial advancement of our understanding of the parasite response to anthropogenic pressures in urbanised areas which are typical on a European scale. Here we describe communities of larval trematodes in two lymnaeid species, Radix auricularia and Lymnaea stagnalis in four man-made interconnected reservoirs of the Ruhr River (Germany) focusing on among- and within-reservoir variations in parasite prevalence and component community composition and structure. RESULTS: The mature reservoir system on the Ruhr River provides an excellent environment for the development of species-rich and abundant trematode communities in Radix auricularia (12 species) and Lymnaea stagnalis (6 species). The lake-adapted R. auricularia dominated numerically over L. stagnalis and played a major role in the trematode transmission in the reservoir system. Both host-parasite systems were dominated by bird parasites (13 out of 15 species) characteristic for eutrophic water bodies. In addition to snail size, two environmental variables, the oxygen content and pH of the water, were identified as important determinants of the probability of infection. Between-reservoir comparisons indicated an advanced eutrophication at Baldeneysee and Hengsteysee and the small-scale within-reservoir variations of component communities provided evidence that larval trematodes may have reflected spatial bird aggregations (infection 'hot spots'). Two life history groupings of dominant species, the 'cyprinid' and 'anatid' parasites, that depict two aspects of progressive eutrophication in this mature reservoir system, were identified. CONCLUSIONS: We conclude that trematode communities in the lake-adapted R. auricularia are better suited for monitoring the effect of environmental change on host-parasite associations in the reservoir system on the Ruhr River and other similar systems due to the important role of this host in trematode transmission in lakes. Whereas variations in trematode community diversity and abundance may indicate the degree of eutrophication on a larger scale (among reservoirs), the infection rates of the two life history groups of dominant species, the 'cyprinid' and 'anatid' assemblages, may be particularly useful in depicting environmental variability, eutrophication effects and infection 'hot spots' on smaller spatial scales. PMID- 20576147 TI - Excavated pulmonary nodules: an unusual clinical presentation of lung metastasis in two cases. AB - BACKGROUND: Excavated pulmonary metastasis are rare. We present two cases of excavated pulmonary nodules proved to be metastases from osteosarcoma and gallblader lymphoma. CASE PRESENTATION: The first one is 39-year-old man in whom cholecystectomy made the diagnosis of primary non-Hodgkin's lymphoma of the gallbladder. He presented in chest CT scan excavated nodules that had been biopsied and confirmed the diagnosis of non hodgkin lymphoma. He underwent 8 courses of chemotherapy CHOP 21 with complete remission. The second one is an 21 years old man who presented a right leg osteoblastic osteosarcoma with only excavated pulmonary nodules in extension assessment. He had 3 courses of polychemotherapy API (doxorubicin, platinum, and ifosfamide) with partial response. Unfortunately, he died following a septic shock.Review of the literature shows that excavated pulmonary nodules as metastasis are rare but we should consider this diagnosis every time we are in front of a cancer. Chest computed tomography is the best diagnosis imaging that could make this diagnosis. Differential diagnosis between benign and malignant bullous lesions is important because surgical excision affects survival in some malignancies. CONCLUSIONS: Although pulmonary nodules are the most common cancer metastasis, a differential diagnosis of a concurrent primary malignancy should always be considered every time we have excavated lesions, even in patients with known malignant disease. Thorough chest evaluation is important, as multiple primary malignancies may occur concomitantly. PMID- 20576148 TI - Efficient cell-free expression with the endogenous E. Coli RNA polymerase and sigma factor 70. AB - BACKGROUND: Escherichia coli cell-free expression systems use bacteriophage RNA polymerases, such as T7, to synthesize large amounts of recombinant proteins. These systems are used for many applications in biotechnology, such as proteomics. Recently, informational processes have been reconstituted in vitro with cell-free systems. These synthetic approaches, however, have been seriously limited by a lack of transcription modularity. The current available cell-free systems have been optimized to work with bacteriophage RNA polymerases, which put significant restrictions to engineer processes related to biological information. The development of efficient cell-free systems with broader transcription capabilities is required to study complex informational processes in vitro. RESULTS: In this work, an efficient cell-free expression system that uses the endogenous E. coli RNA polymerase only and sigma factor 70 for transcription was prepared. Approximately 0.75 mg/ml of Firefly luciferase and enhanced green fluorescent protein were produced in batch mode. A plasmid was optimized with different regulatory parts to increase the expression. In addition, a new eGFP was engineered that is more translatable in cell-free systems than the original eGFP. The protein production was characterized with three different adenosine triphosphate (ATP) regeneration systems: creatine phosphate (CP), phosphoenolpyruvate (PEP), and 3-phosphoglyceric acid (3-PGA). The maximum protein production was obtained with 3-PGA. Preparation of the crude extract was streamlined to a simple routine procedure that takes 12 hours including cell culture. CONCLUSIONS: Although it uses the endogenous E. coli transcription machinery, this cell-free system can produce active proteins in quantities comparable to bacteriophage systems. The E. coli transcription provides much more possibilities to engineer informational processes in vitro. Many E. coli promoters/operators specific to sigma factor 70 are available that form a broad library of regulatory parts. In this work, cell-free expression is developed as a toolbox to design and to study synthetic gene circuits in vitro. PMID- 20576149 TI - Fenoldopam use in a burn intensive care unit: a retrospective study. AB - BACKGROUND: Fenoldopam mesylate is a highly selective dopamine-1 receptor agonist approved for the treatment of hypertensive emergencies that may have a role at low doses in preserving renal function in those at high risk for or with acute kidney injury (AKI). There is no data on low-dose fenoldopam in the burn population. The purpose of our study was to describe our use of low-dose fenoldopam (0.03-0.09 mug/kg/min) infusion in critically ill burn patients with AKI. METHODS: We performed a retrospective analysis of consecutive patients admitted to our burn intensive care unit (BICU) with severe burns from November 2005 through September 2008 who received low-dose fenoldopam. Data obtained included systolic blood pressure, serum creatinine, vasoactive medication use, urine output, and intravenous fluid. Patients on concomitant continuous renal replacement therapy were excluded. Modified inotrope score and vasopressor dependency index were calculated. One-way analysis of variance with repeated measures, Wilcoxson signed rank, and chi-square tests were used. Differences were deemed significant at p < 0.05. RESULTS: Seventy-seven patients were treated with low-dose fenoldopam out of 758 BICU admissions (10%). Twenty (26%) were AKI network (AKIN) stage 1, 14 (18%) were AKIN stage 2, 42 (55%) were AKIN stage 3, and 1 (1%) was AKIN stage 0. Serum creatinine improved over the first 24 hours and continued to improve through 48 hours (p < 0.05). There was an increase in systolic blood pressure in the first 24 hours that was sustained through 48 hours after initiation of fenoldopam (p < 0.05). Urine output increased after initiation of fenoldopam without an increase in intravenous fluid requirement (p < 0.05; p = NS). Modified inotrope score and vasopressor dependency index both decreased over 48 hours (p < 0.0001; p = 0.0012). CONCLUSIONS: These findings suggest that renal function was preserved and that urine output improved without a decrease in systolic blood pressure, increase in vasoactive medication use, or an increase in resuscitation requirement in patients treated with low-dose fenoldopam. A randomized controlled trial is required to establish the efficacy of low-dose fenoldopam in critically ill burn patients with AKI. PMID- 20576150 TI - The state of pediatric asthma in Chicago's Humboldt Park: a community-based study in two local elementary schools. AB - BACKGROUND: Pediatric asthma is a serious public health problem in Chicago and has been designated a high priority concern by residents of Chicago's Humboldt Park, a diverse community area with a large number of Puerto Rican, African American, and Mexican American families. METHODS: In May 2009, following the principles of community-based participatory research, a cross-sectional asthma screening survey was administered to adult caregivers of children attending two Humboldt Park elementary schools. Data were analyzed to determine the prevalence of diagnosed and probable asthma as well as the degree of asthma control among affected children; associations between asthma outcomes and mutable triggers were evaluated. RESULTS: Surveys from 494 children were evaluated. Physician-diagnosed asthma was reported for 24.9% of children and probable asthma identified in an additional 16.2% of children. Asthma was poorly or moderately controlled in 60.0% of diagnosed children. Smoking occurred inside 25.0% of households and 75.0% of caregivers reported idling of vehicles in their community. Report of general stress among caregivers, stress due to community crime, and/or an inability to cope with everyday life were significantly and positively associated with poor asthma morbidity and control among affected children. CONCLUSIONS: Despite high prevalence rates and poor asthma morbidity and control in Humboldt Park, the association of these measures with mutable variables is promising. A community based asthma intervention to address the issues identified in this study is needed to affect positive change. PMID- 20576152 TI - Extracting samples of high diversity from thematic collections of large gene banks using a genetic-distance based approach. AB - BACKGROUND: Breeding programs are usually reluctant to evaluate and use germplasm accessions other than the elite materials belonging to their advanced populations. The concept of core collections has been proposed to facilitate the access of potential users to samples of small sizes, representative of the genetic variability contained within the gene pool of a specific crop. The eventual large size of a core collection perpetuates the problem it was originally proposed to solve. The present study suggests that, in addition to the classic core collection concept, thematic core collections should be also developed for a specific crop, composed of a limited number of accessions, with a manageable size. RESULTS: The thematic core collection obtained meets the minimum requirements for a core sample - maintenance of at least 80% of the allelic richness of the thematic collection, with, approximately, 15% of its size. The method was compared with other methodologies based on the M strategy, and also with a core collection generated by random sampling. Higher proportions of retained alleles (in a core collection of equal size) or similar proportions of retained alleles (in a core collection of smaller size) were detected in the two methods based on the M strategy compared to the proposed methodology. Core sub collections constructed by different methods were compared regarding the increase or maintenance of phenotypic diversity. No change on phenotypic diversity was detected by measuring the trait "Weight of 100 Seeds", for the tested sampling methods. Effects on linkage disequilibrium between unlinked microsatellite loci, due to sampling, are discussed. CONCLUSIONS: Building of a thematic core collection was here defined by prior selection of accessions which are diverse for the trait of interest, and then by pairwise genetic distances, estimated by DNA polymorphism analysis at molecular marker loci. The resulting thematic core collection potentially reflects the maximum allele richness with the smallest sample size from a larger thematic collection. As an example, we used the development of a thematic core collection for drought tolerance in rice. It is expected that such thematic collections increase the use of germplasm by breeding programs and facilitate the study of the traits under consideration. The definition of a core collection to study drought resistance is a valuable contribution towards the understanding of the genetic control and the physiological mechanisms involved in water use efficiency in plants. PMID- 20576151 TI - The effect of abductor muscle and anterior-posterior hip contact load simulation on the in-vitro primary stability of a cementless hip stem. AB - BACKGROUND: In-vitro mechanical tests are commonly performed to assess pre clinically the effect of implant design on the stability of hip endoprostheses. There is no standard protocol for these tests, and the forces applied vary between studies. This study examines the effect of the abductor force with and without application of the anterior-posterior hip contact force in the in-vitro assessment of cementless hip implant stability. METHODS: Cementless stems (VerSys Fiber Metal) were implanted in twelve composite femurs which were divided into two groups: group 1 (N = 6) was loaded with the hip contact force only, whereas group 2 (N = 6) was additionally subjected to an abductor force. Both groups were subjected to the same cranial-caudal hip contact force component, 2.3 times body weight (BW) and each specimen was subjected to three levels of anterior-posterior hip contact load: 0, -0.1 to 0.3 BW (walking), and -0.1 to 0.6 BW (stair climbing). The implant migration and micromotion relative to the femur was measured using a custom-built system comprised of 6 LVDT sensors. RESULTS: Substantially higher implant motion was observed when the anterior-posterior force was 0.6BW compared to the lower anterior-posterior load levels, particularly distally and in retroversion. The abductor load had little effect on implant motion when simulating walking, but resulted in significantly less motion than the hip contact force alone when simulating stair climbing. CONCLUSIONS: The anterior-posterior component of the hip contact load has a significant effect on the axial motion of the stem relative to the bone. Inclusion of the abductor force had a stabilizing effect on the implant motion when simulating stair climbing. PMID- 20576153 TI - Reversible bone pain and symmetric bone scan uptake in a dialysis patient treated with cinacalcet: a case report. AB - INTRODUCTION: The medical management of secondary hyperparathyroidism in patients with end-stage renal disease involves a combination of dietary restrictions, phosphate binders, active vitamin D analogs, and calcimimetics. CASE PRESENTATION: We report the case of a 36-year-old Hispanic dialysis patient, originally from Cuba and now residing in the USA, who developed severe bone pain and muscle twitching after starting low dose cinacalcet, despite normal pre dialysis ionized calcium and elevated parathyroid hormone. The clinical symptoms correlated with increased symmetrical uptake on bone scan that resolved rapidly upon discontinuation of cinacalcet. CONCLUSION: Cinacalcet may induce severe bone pain and a unique bone scan uptake pattern in hemodialysis patients. PMID- 20576154 TI - Can egg donor selection be improved?--A pilot study. AB - BACKGROUND: Accurate assessments of ovarian reserve (OR) in egg donor candidates are crucial for maximal donor selection. This study assesses whether recently reported new methods of OR assessment by age-specific (as-), rather than non-as (nas-) hormones, follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and triple nucleotide (CGG) repeats on the FMR1 (fragile X) gene have the potential of improving egg donor selection. METHODS: Seventy-three consecutive egg donor candidates (candidates), amongst those 21 who reached egg retrieval (donors), were prospectively investigated for as-FSH, as-AMH and number of CGG repeats. Abnormal findings were assessed in candidates and donors and oocyte yields in the latter were statistically associated with abnormal FSH and AMH (>or< 95% CI of as-levels) and with normal/abnormal numbers of CGG repeats (normal range 26-32). RESULTS: Amongst candidates mean as-AMH was 3.8 +/- 2.8 ng/mL (37.0% normal, 3.0 +/- 0.7 ng/mL; 26.6% low, 1.5 +/- 0.5 ng/mL; and 37.0% high, 5.8 +/- 2.2 ng/mL). AMH among donors was 4.2 +/- 1.7 ng/mL (33.3% normal, 14.3% low, and 52.4% high), yielding 17.8 +/- 7.2 oocytes, 42.9% in normal range (10-15), 9.5% in low (less than or equal to 9) and 47.6.% in high range (16-32). Candidates in 41.9% and donors in 38.1% demonstrated normal CGG counts; the remained were mostly heterozygous abnormal. DISCUSSION: Prospective assessment of even carefully prescreened candidates and donors still demonstrates shortcomings on both ends of the OR spectrum. Utilization of ovarian reserve testing methods, like as-hormones and CGG repeats on the FMR1 gene have potential of improving candidate selections. PMID- 20576155 TI - Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. AB - INTRODUCTION: Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared with related conditions. METHODS: The 199 patients with JIA (23 sJIA and 176 non-sJIA) and 38 controls were studied. PBMCs were isolated and analyzed for multiple surface antigens with flow cytometry and for gene-expression profiles. The proportions of different PBMC subpopulations were compared among sJIA, non-sJIA patients, and controls and subsequently correlated with the strength of the erythropoiesis signature. Additional gene expression data from patients with familial hemophagocytic lymphohistiocytosis (FHLH) and from a published sJIA cohort were analyzed to determine whether the erythropoiesis signature was present. RESULTS: Patients with sJIA had significantly increased proportions of immature cell populations, including CD34+ cells, correlating highly with the strength of the erythropoiesis signature. The erythropoiesis signature strongly overlapped with the gene-expression pattern in purified immature erythroid precursors. The expansion of immature cells was most prominently seen in patients with sJIA and anemia, even in the absence of reticulocytosis. Patients with non-sJIA and anemia did not exhibit the erythropoiesis signature. The erythropoiesis signature was found to be prominent in patients with FHLH and in a published cohort of patients with active sJIA, but not in patients with inactive sJIA. CONCLUSIONS: An erythropoiesis signature in active sJIA is associated with the expansion of CD34+ cells, also is seen in some patients with FHLH and infection, and may be an indicator of ineffective erythropoiesis and hemophagocytosis due to hypercytokinemia. PMID- 20576156 TI - Hyperinsulinemia improves ischemic LV function in insulin resistant subjects. AB - BACKGROUND: Glucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR. METHODS: 24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC. RESULTS: HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR. CONCLUSIONS: Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy. PMID- 20576157 TI - Local alignment of generalized k-base encoded DNA sequence. AB - BACKGROUND: DNA sequence comparison is a well-studied problem, in which two DNA sequences are compared using a weighted edit distance. Recent DNA sequencing technologies however observe an encoded form of the sequence, rather than each DNA base individually. The encoded DNA sequence may contain technical errors, and therefore encoded sequencing errors must be incorporated when comparing an encoded DNA sequence to a reference DNA sequence. RESULTS: Although two-base encoding is currently used in practice, many other encoding schemes are possible, whereby two ore more bases are encoded at a time. A generalized k-base encoding scheme is presented, whereby feasible higher order encodings are better able to differentiate errors in the encoded sequence from true DNA sequence variants. A generalized version of the previous two-base encoding DNA sequence comparison algorithm is used to compare a k-base encoded sequence to a DNA reference sequence. Finally, simulations are performed to evaluate the power, the false positive and false negative SNP discovery rates, and the performance time of k base encoding compared to previous methods as well as to the standard DNA sequence comparison algorithm. CONCLUSIONS: The novel generalized k-base encoding scheme and resulting local alignment algorithm permits the development of higher fidelity ligation-based next generation sequencing technology. This bioinformatic solution affords greater robustness to errors, as well as lower false SNP discovery rates, only at the cost of computational time. PMID- 20576158 TI - Mental health first aid training for high school teachers: a cluster randomized trial. AB - BACKGROUND: Mental disorders often have their first onset during adolescence. For this reason, high school teachers are in a good position to provide initial assistance to students who are developing mental health problems. To improve the skills of teachers in this area, a Mental Health First Aid training course was modified to be suitable for high school teachers and evaluated in a cluster randomized trial. METHODS: The trial was carried out with teachers in South Australian high schools. Teachers at 7 schools received training and those at another 7 were wait-listed for future training. The effects of the training on teachers were evaluated using questionnaires pre- and post-training and at 6 months follow-up. The questionnaires assessed mental health knowledge, stigmatizing attitudes, confidence in providing help to others, help actually provided, school policy and procedures, and teacher mental health. The indirect effects on students were evaluated using questionnaires at pre-training and at follow-up which assessed any mental health help and information received from school staff, and also the mental health of the student. RESULTS: The training increased teachers' knowledge, changed beliefs about treatment to be more like those of mental health professionals, reduced some aspects of stigma, and increased confidence in providing help to students and colleagues. There was an indirect effect on students, who reported receiving more mental health information from school staff. Most of the changes found were sustained 6 months after training. However, no effects were found on teachers' individual support towards students with mental health problems or on student mental health. CONCLUSIONS: Mental Health First Aid training has positive effects on teachers' mental health knowledge, attitudes, confidence and some aspects of their behaviour. TRIAL REGISTRATION: ACTRN12608000561381. PMID- 20576160 TI - Representations of cycling in metropolitan newspapers--changes over time and differences between Sydney and Melbourne, Australia. AB - BACKGROUND: Cycling is important for health, transport, environmental and economic reasons. Newspaper reporting of cycling reflects and can influence public and policy maker attitudes towards resource allocation for cycling and cycling infrastructure, yet such coverage has not been systematically examined. METHODS: The Factiva electronic news archive was searched for articles referring to cycling published in four major metropolitan newspapers--two in Sydney and two in Melbourne, Australia, in the years from 1998 until 2008. After excluding articles not about cycling, there were 61 articles published in 1998, 45 in 1999, 51 in 2003, 82 in 2007 and 87 in 2008. Each article was coded for positive or negative orientation, and for framing of cyclists and cycling. Inter-rater reliability was calculated on a sample of 30 articles. RESULTS: Over the past decade there has been an increase in the reporting of cycling in the major newspapers in Sydney and Melbourne (from 106 in 1998/99 to 169 stories in 2007/08), with a significant increase in reporting of cycling in Melbourne, from 49 to 103 stories (p = 0.04). Recent reporting of cycling was generally positive (47% of articles, compared with 30% of articles which were negative) and focused on benefits such as health and the environment. Three quarters of negative stories involved injury or death of a cyclist. The Sydney based The Daily Telegraph reported the most negative stories (n = 60). We found positive framing of 'cycling' was more widespread than negative, whereas framing of 'cyclists' was more negative than positive. CONCLUSIONS: Quantity of reporting of cycling varies over time and by newspaper, and even between newspapers in different cities owned by the same media company. News coverage appears to reflect developments in the different cities, with increases in positive reporting of cycling in Melbourne following increases in cycling in that city. Negative cycling newspaper stories may deter people from considering cycling as a transport option, but real physical or political improvements to the cycling environment may be necessary before coverage becomes more positive. PMID- 20576159 TI - Interpretation of response categories in patient-reported rating scales: a controlled study among people with Parkinson's disease. AB - BACKGROUND: Unambiguous interpretation of ordered rating scale response categories requires distinct meanings of category labels. Also, summation of item responses into total scores assumes equal intervals between categories. While studies have identified problems with rating scale response category functioning there is a paucity of empirical studies regarding how respondents interpret response categories. We investigated the interpretation of commonly used rating scale response categories and attempted to identify distinct and roughly equally spaced response categories for patient-reported rating scales in Parkinson's disease (PD) and age-matched control subjects. METHODS: Twenty-one rating scale response categories representing frequency, intensity and level of agreement were presented in random order to 51 people with PD (36 men; mean age, 66 years) and 36 age-matched controls (14 men; mean age, 66). Respondents indicated their interpretation of each category on 100-mm visual analog scales (VAS) anchored by Never--Always, Not at all--Extremely, and Totally disagree--Completely agree. VAS values were compared between groups, and response categories with mean values and non-overlapping 95% CIs corresponding to equally spaced locations on the VAS line were sought to identify the best options for three-, four-, five-, and six category scales. RESULTS: VAS values did not differ between the PD and control samples (P = 0.286) or according to educational level (P = 0.220), age (P = 0.220), self-reported physical functioning (P = 0.501) and mental health (P = 0.238), or (for the PD sample) PD duration (P = 0.213) or presence of dyskinesias (P = 0.212). Attempts to identify roughly equally spaced response categories for three-, four-, five-, and six-category scales were unsuccessful, as the 95% CIs of one or several of the identified response categories failed to include the criterion values for equal distances. CONCLUSIONS: This study offers an evidence base for selecting more interpretable patient-reported rating scale response categories. However, problems associated with raw rating scale data, primarily related to their ordinal structure also became apparent. This argues for the application of methodologies such as Rasch measurement. Rating scale response categories need to be treated with rigour in the construction and analysis of rating scales. PMID- 20576161 TI - Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report. AB - A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74 year-old Japanese male. The cystic lesion, measuring 3.5 x 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 x 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum. PMID- 20576162 TI - The design and protocol of heat-sensitive moxibustion for knee osteoarthritis: a multicenter randomized controlled trial on the rules of selecting moxibustion location. AB - BACKGROUND: Knee osteoarthritis is a major cause of pain and functional limitation. Complementary and alternative medical approaches have been employed to relieve symptoms and to avoid the side effects of conventional medication. Moxibustion has been widely used to treat patients with knee osteoarthritis. Our past researches suggested heat-sensitive moxibustion might be superior to the conventional moxibustion. Our objective is to investigate the effectiveness of heat-sensitive moxibustion compared with conventional moxibustion or conventional drug treatment. METHODS: This study consists of a multi-centre (four centers in China), randomised, controlled trial with three parallel arms (A: heat-sensitive moxibustion; B: conventional moxibustion; C: conventional drug group). The moxibustion locations are different from A and B. Group A selects heat sensitization acupoint from the region consisting of Yin Lingquan(SP9), Yang Lingquan(GB34), Liang Qiu(ST34), and Xue Hai (SP10). Meanwhile, fixed acupoints are used in group B, that is Xi Yan (EX-LE5) and He Ding (EX-LE2). The conventional drug group treats with intra-articular Sodium Hyaluronate injection. The outcome measures above will be assessed before the treatment, the 30 days of the last moxibustion session and 6 months after the last moxibustion session. DISCUSSION: This trial will utilize high quality trial methodologies in accordance with CONSORT guidelines. It will provide evidence for the effectiveness of moxibustion as a treatment for moderate and severe knee osteoarthritis. Moreover, the result will clarify the rules of heat-sensitive moxibustion location to improve the therapeutic effect with suspended moxibustion, and propose a new concept and a new theory of moxibustion to guide clinical practices. TRIAL REGISTRATION: The trial is registered at Controlled Clinical Trials: ChiCTR-TRC-00000600. PMID- 20576163 TI - Total smoking bans in psychiatric inpatient services: a survey of perceived benefits, barriers and support among staff. AB - BACKGROUND: The introduction of total smoking bans represents an important step in addressing the smoking and physical health of people with mental illness. Despite evidence indicating the importance of staff support in the successful implementation of smoking bans, limited research has examined levels of staff support prior to the implementation of a ban in psychiatric settings, or factors that are associated with such support. This study aimed to examine the views of psychiatric inpatient hospital staff regarding the perceived benefits of and barriers to implementation of a successful total smoking ban in mental health services. Secondly, to examine the level of support among clinical and non clinical staff for a total smoking ban. Thirdly, to examine the association between the benefits and barriers perceived by clinicians and their support for a total smoking ban in their unit. METHODS: Cross-sectional survey of both clinical and non-clinical staff in a large inpatient psychiatric hospital immediately prior to the implementation of a total smoking ban. RESULTS: Of the 300 staff, 183 (61%) responded. Seventy-three (41%) of total respondents were clinical staff, and 110 (92%) were non-clinical staff. More than two-thirds of staff agreed that a smoking ban would improve their work environment and conditions, help staff to stop smoking and improve patients' physical health. The most prevalent clinician perceived barriers to a successful total smoking ban related to fear of patient aggression (89%) and patient non-compliance (72%). Two thirds (67%) of all staff indicated support for a total smoking ban in mental health facilities generally, and a majority (54%) of clinical staff expressed support for a ban within their unit. Clinical staff who believed a smoking ban would help patients to stop smoking were more likely to support a smoking ban in their unit. CONCLUSIONS: There is a clear need to more effectively communicate to staff the evidence that consistently applied smoking bans do not increase patient aggression. There is also a need to communicate the benefits of smoking bans in aiding the delivery of smoking cessation care, and the benefits of both smoking bans and such care in aiding patients to stop smoking. PMID- 20576164 TI - The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity. AB - BACKGROUND: We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. RESULTS: FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures as determined by annexin V/propidium iodide staining and immunoblot analysis. FLLL32 treatment reduced expression of STAT3-target genes, induced caspase-dependent apoptosis, and reduced mitochondrial membrane potential. FLLL32 displayed specificity for STAT3 over other homologous STAT proteins. In contrast to other STAT3 pathway inhibitors (WP1066, JSI-124, Stattic), FLLL32 did not abrogate IFN gamma-induced pSTAT1 or downstream STAT1-mediated gene expression as determined by Real Time PCR. In addition, FLLL32 did not adversely affect the function or viability of immune cells from normal donors. In peripheral blood mononuclear cells (PBMCs), FLLL32 inhibited IL-6-induced pSTAT3 but did not reduce signaling in response to immunostimulatory cytokines (IFN-gamma, IL 2). Treatment of PBMCs or natural killer (NK) cells with FLLL32 also did not decrease viability or granzyme b and IFN-gamma production when cultured with K562 targets as compared to vehicle (DMSO). CONCLUSIONS: These data suggest that FLLL32 represents a lead compound that could serve as a platform for further optimization to develop improved STAT3 specific inhibitors for melanoma therapy. PMID- 20576165 TI - Geographical origin of Plasmodium vivax in the Republic of Korea: haplotype network analysis based on the parasite's mitochondrial genome. AB - BACKGROUND: The Republic of Korea (South Korea) is one of the countries where vivax malaria had been successfully eradicated by the late 1970s. However, re emergence of vivax malaria in South Korea was reported in 1993. Several epidemiological studies and some genetic studies using antigenic molecules of Plasmodium vivax in the country have been reported, but the evolutionary history of P. vivax has not been fully understood. In this study, the origin of the South Korean P. vivax population was estimated by molecular phylogeographic analysis. METHODS: A haplotype network analysis based on P. vivax mitochondrial (mt) DNA sequences was conducted on 11 P. vivax isolates from South Korea and another 282 P. vivax isolates collected worldwide. RESULTS: The network analysis of P. vivax mtDNA sequences showed that the coexistence of two different groups (A and B) in South Korea. Groups A and B were identical or close to two different populations in southern China. CONCLUSIONS: Although the direct introduction of the two P. vivax populations in South Korea were thought to have been from North Korea, the results of this analysis suggest the genealogical origin to be the two different populations in southern China. PMID- 20576166 TI - Serum glutamine, set-shifting ability and anorexia nervosa. AB - BACKGROUND: Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine) are associated with set shifting ability in people with acute AN and those after recovery. METHODS: Serum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Serum glutamine concentrations in the AN group (1,310.2 +/- 265.6 muM, mean +/- SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 +/- 152.7 muM, mean +/- SD) (F(2, 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4). Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI) and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting. CONCLUSIONS: Serum concentrations of glutamine may be a biomarker of illness severity in people with AN. It does not appear to be directly associated with changes in executive function. PMID- 20576167 TI - Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells. AB - BACKGROUND: The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein. METHODS: To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns. RESULTS: Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-kappaB target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells. CONCLUSIONS: We conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas. PMID- 20576170 TI - Isolation of lactoperoxidase using different cation exchange resins by batch and column procedures. AB - Lactoperoxidase (LP) was isolated from whey protein by cation-exchange using Carboxymethyl resin (CM-25C) and Sulphopropyl Toyopearl resin (SP-650C). Both batch and column procedures were employed and the adsorption capacities and extraction efficiencies were compared. The resin bed volume to whey volume ratios were 0.96:1.0 for CM-25C and 0.64:1.0 for SP-650 indicating higher adsorption capacity of SP-650 compared with CM-25C. The effluent LP activity depended on both the enzyme activity in the whey and the amount of whey loaded on the column within the saturation limits of the resin. The percentage recovery was high below the saturation point and fell off rapidly with over-saturation. While effective recovery was achieved with column extraction procedures, the recovery was poor in batch procedures. The whey-resin contact time had little impact on the enzyme adsorption. SDS PAGE and HPLC analyses were also carried out, the purity was examined and the proteins characterised in terms of molecular weights. Reversed phase HPLC provided clear distinction of the LP and lactoferrin (LF) peaks. The enzyme purity was higher in column effluents compared with batch effluents, judged on the basis of the clarity of the gel bands and the resolved peaks in HPLC chromatograms. PMID- 20576169 TI - Blood and milk immune and inflammatory profiles in periparturient dairy cows showing a different liver activity index. AB - This paper reports the results of a study that aimed to assess whether liver functionality defined by liver activity index (LAI) is associated with inflammatory and immune parameters in blood and milk. LAI is an index including the average blood levels of albumin, lipoproteins and retinol-binding protein measured three times in the first month of lactation (at 5, 15 and 30 days in milk). The aim was to assess the relationship of this index with blood and udder immune and inflammatory status as a means of identifying as early as possible cows at risk of disease. The research was carried out using 10 multiparous Italian-Friesian dairy cows of average genetic merit. Cows were retrospectively ranked in three groups according the LAI level. Blood samplings were performed at different intervals before and after calving; quarter milk samples were taken only after calving with the same schedule as blood samples. Leucocytes, oxidative burst, blood lysozyme and N-acetyl-beta-d-glucosaminidase (NAGase) curves showed large overlapping among the three LAI group curves during the follow-up period. Four blood (complement, sialic acid, haptoglobin and reactive oxygen metabolites) and three milk (somatic cell count, lysozyme and NAGase) parameters showed larger and more consistent differences among LAI groups. Complement showed higher values and sialic acid showed lower values in high LAI group when compared with the other two LAI groups. Two other markers of inflammatory status (haptoglobin and reactive oxygen metabolites) showed the lowest values in high LAI cows. A consistent and significant reduction of milk NAGase and milk lysozyme in high LAI group was observed. The results suggest that cows with the highest liver functionality index have also the highest levels of some immune markers and the lowest levels for inflammatory markers at blood (already before calving) and mammary levels. Finally, cows with low LAI index, being more susceptible to metabolic and infectious diseases, should be carefully monitored to identify as early as possible the development of a disease. PMID- 20576168 TI - Non-additive effects of RBP4, ESR1 and IGF2 polymorphisms on litter size at different parities in a Chinese-European porcine line. AB - BACKGROUND: The aim of this work was to study the effects on litter size of variants of the porcine genes RBP4, ESR1 and IGF2, currently used in genetic tests for different purposes. Moreover, we investigated a possible effect of the interaction between RBP4-MspI and ESR1-PvuII polymorphisms. The IGF2-intron3 G3072A polymorphism is actually used to select lean growth, but other possible effects of this polymorphism on reproductive traits need to be evaluated. METHODS: Detection of polymorphisms in the genomic and cDNA sequences of RBP4 gene was carried out. RBP4-MspI and IGF2-intron3-G3072A were genotyped in a hyperprolific Chinese-European line (Tai-Zumu) and three new RBP4 polymorphisms were genotyped in different pig breeds. A bivariate animal model was implemented in association analyses considering the number of piglets born alive at early (NBA12) and later parities (NBA3+ ) as different traits. A joint analysis of RBP4 MspI and ESR1-PvuII was performed to test their possible interaction. In the IGF2 analysis, paternal or maternal imprinting effects were also considered. RESULTS: Four different RBP4 haplotypes were detected (TGAC, GGAG, GAAG and GATG) in different pig breeds and wild boars. A significant interaction effect between RBP4-MspI and ESR1-PvuII polymorphisms of 0.61 +/- 0.29 piglets was detected on NBA3+. The IGF2 analysis revealed a significant increase on NBA3+ of 0.74 +/- 0.37 piglets for the paternally inherited allele A. CONCLUSIONS: All the analyzed pig and wild boar populations shared one of the four detected RBP4 haplotypes. This suggests an ancestral origin of the quoted haplotype. The joint use of RBP4 MspI and ESR1-PvuII polymorphisms could be implemented to select for higher prolificacy in the Tai-Zumu line. In this population, the paternal allele IGF2 intron3-3072A increased litter size from the third parity. The non-additive effects on litter size reported here should be tested before implementation in other pig breeding schemes. PMID- 20576171 TI - Systematics and molecular phylogeny of two African stem borer genera, Sciomesa Tams & Bowden and Carelis Bowden (Lepidoptera: Noctuidae). AB - Currently, the systematics of the African noctuid stem borers of the subtribe Sesamiina, which include major pests of cereals, is confused. In addition, their ecology is poorly known, as are the factors influencing their evolution. In this paper, we address these shortcomings for two genera of the Sesamiina, Sciomesa Tams & Bowden and Carelis Bowden. Mixed Bayesian phylogenetic analysis, which included their host plants and two mitochondrial genes, showed the genus Sciomesa to be polyphyletic. Two new genera were created, Pirateolea and Feraxinia. The genus Carelis proved to be paraphyletic and was subdivided into two sub-genera. The genera Sciomesa, Carelis and Pirateolea (named the 'Sciomesa genus group') share morphological traits, and the phylogenetic analysis showed that they had a common ancestor living on Cyperaceae and that they were distant from the genus Feraxinia belonging to another clade which had an ancestor living on Poaceae. Seven new species were described: Sciomesa gnosia sp. n., Sciomesia bua sp. n., Pirateolea nola gen. n, sp. n., Feraxinia serena gen. n., sp. n., Carelis australis sp. n., Carelis transversa sp. n. and Carelis agnae sp. n. Ten species were sunk as synonyms: Sciomesa mesoscia (Hampson) syn. n., Sciomesa mirifica Laporte syn. n., Sciomesa constantini Laporte syn. n. and Sciomesa etchecopari Laporte syn. n. are synonyms of Sciomesa mesophaea (Aurivillius); Acrapex sparsipucta Laporte syn. n. is a synonym of Sciomesa excelsa (Laporte) comb. n.; Acrapex congitae Laporte syn. n., Sesamia minuta Laporte syn. n. and Sesamia minuscula Laporte syn. n. are synonyms of Sciomesa boulardi (Laporte) comb. n.; Acrapex bryae Laporte syn. n. and Acrapex fayei Laporte syn. n. are synonyms of Feraxinia jemjemensis (Laporte) comb. n. Eleven new combinations were created: Sciomesa excelsa (Laporte) comb. n., Sciomesa boulardi (Laporte) comb. n., Sciomesa punctipennis (Kruger) comb. n., Pirateolea piscator (Fletcher) comb. n., Pirateolea argocyma (Fletcher) comb. n., Pirateolea cyclophora (Fletcher) comb. n., Pirateolea ochroneura (Fletcher) comb. n., Pirateolea funebris (Kruger) comb. n., Feraxinia nyei (Fletcher) comb. n., Feraxinia jemjemensis (Laporte) comb. n. and Carelis biluma (Nye) comb. n. PMID- 20576172 TI - The Linguistic Affiliation Constraint and phoneme recognition in diglossic Arabic. AB - This study tested the effect of the phoneme's linguistic affiliation (Standard Arabic versus Spoken Arabic) on phoneme recognition among five-year-old Arabic native speaking kindergarteners (N=60). Using a picture selection task of words beginning with the same phoneme, and through careful manipulation of the phonological properties of target phonemes and distractors, the study showed that children's recognition of Standard phonemes was poorer than that of Spoken phonemes. This finding was interpreted as indicating a deficiency in the phonological representations of Standard words. Next, the study tested two hypotheses regarding the specific consequences of under-specified phonological representations: phonological encoding versus phonological processing. These hypotheses were addressed through an analysis of the relative power of distractors. The findings revealed that children's difficulty in accessing Standard Arabic phonemes was due to a difficulty in the phonological encoding of Standard words. We discuss the implications of the findings for language and literacy development in diglossic Arabic. PMID- 20576173 TI - Developmental cascades. PMID- 20576174 TI - Systems theory and cascades in developmental psychopathology. AB - In the wake of prominent theoreticians in developmental science, whose contributions we review in this article, many developmental psychologists came to endorse a systems approach to understanding how the individual, as it develops, establishes functional relationships to social ecological contexts that from birth to school entry rapidly increase in complexity. The concept of developmental cascade has been introduced in this context to describe lawful processes by which antecedent conditions may be related with varying probabilities to specified outcomes. These are understood as processes by which function at one level or in one domain of behavior affect the organization of competency in later developing domains of general adaptation. Here we propose a developmental sequence by which the developing child acquires regulative capacities that are key to adjustment to a society that demands considerable control of emotional and cognitive functions early in life. We report empirical evidence showing that the acquisition of regulative capacities may be understood as a cascade of shifts in control parameters induced by the progressive integration of biological, transactional, and socioaffective systems over development. We conclude by suggesting how the developmental process may be accessed for effective intervention in populations deemed "at risk" for later problems of psychosocial adjustment. PMID- 20576177 TI - Transactional relations across contextual strain, parenting quality, and early childhood regulation and adaptation in a high-risk sample. AB - This investigation examined transactional relations across contextual strain, parenting quality, and child adjustment in 209 mothers and children at 24, 42, and 72 months of age. Independent ratings of mothers' stressful life events, social support, and relationship quality provided an objective measure of maternal contextual strain. Observers evaluated parenting quality during parent child interactions at each time point. Child regulatory functioning during laboratory tasks at 24 and 42 months was evaluated by independent observers based on both behavioral (e.g., noncompliance, distractibility) and emotional (e.g., frustration, anger) indices. At 72 months, teachers reported on children's externalizing behaviors, and children completed objective measures of academic achievement. Nested path analyses were used to evaluate increasingly complex models of influence, including transactional relations between child and parent, effects from contextual strain to parenting and child adaptation, and reciprocal effects from child and parent behavior to contextual strain. Over and above stability within each domain and cross-sectional cross-domain covariation, significant paths emerged from maternal contextual strain to subsequent child adjustment. Bidirectional relations between parenting and child adjustment were especially prominent among boys. These findings counter unidirectional models of parent-mediated contextual effects by highlighting the direct influences of contextual strain and parent-child transactions on early childhood behavioral and academic adjustment, respectively. PMID- 20576175 TI - Relations among maternal socialization, effortful control, and maladjustment in early childhood. AB - In a sample of 18-, 30-, and 42-month-olds, the relations among parenting, effortful control (EC), and maladjustment were examined. Parenting was assessed with mothers' reports and observations; EC was measured with mothers' and caregivers' reports, as well as a behavioral task; and externalizing and internalizing symptoms were assessed with parents' and caregivers' reports. Although 18-month unsupportive (vs. supportive) parenting negatively predicted EC at 30 months, when the stability of these variables was taken into account, there was no evidence of additional potentially causal relations between these two constructs. Although EC was negatively related to both internalizing and externalizing problems within all three ages as well as across 1 year, EC did not predict maladjustment once the stability of the constructs and within time covariation between the constructs were taken into account. In addition, externalizing problems at 30 months negatively predicted EC at 42 months, and internalizing problems at 30 months positively predicted EC at 42 months, but only when the effects of externalizing on EC were controlled. The findings are discussed in terms of the reasons for the lack of causal relations over time. PMID- 20576178 TI - Competence and psychopathology: cascade effects in the NICHD Study of Early Child Care and Youth Development. AB - Existing longitudinal research on the interplay between externalizing problems, internalizing problems, and academic and social competence has documented "cascading" effects from early aggressive/disruptive behavior through impairments in competence, leading to symptoms of depression and anxiety. The primary aim of the current study was to replicate such work using the NICHD Study of Early Child Care and Youth Development while also extending the developmental window of investigation of cascades back into early childhood. Participating families (N = 1,160) completed questionnaire measures of externalizing, internalizing, and social competence (maternal report), as well as individual assessment of academic achievement, spanning five time points from age 54 months through age 15 years. A series of nested structural equation models tested predicted links across various domains of competence and psychopathology. Results were consistent with prior research, demonstrating cross-domain effects from early externalizing problems through effects on both academic and social competence into later internalizing problems. Effects held across gender and were largely unaffected by inclusion of socioeconomic status, early caregiving, and early cognitive ability as covariates in the model. PMID- 20576176 TI - Early trajectories of interparental conflict and externalizing problems as predictors of social competence in preadolescence. AB - Consistent with developmental cascade notions, the present study investigated (a) associations between trajectories of interparental conflict and early externalizing problems during childhood and (b) early trajectories of externalizing problems as a pathway by which interparental conflict impacts children's social competence in preadolescence. Participants were 235 children and their parents and teachers. Children were assessed annually for 3 years, beginning when they were in kindergarten. Parents provided reports of interparental conflict and child externalizing problems. Children's social competence (prosocial behavior, social problems) was assessed approximately 5 years later via parent and teacher reports. Results from parallel process models indicated that changes in interparental conflict were positively associated with changes in externalizing problems during childhood. Further, demonstrating pathways consistent with notions of developmental cascades, early trajectories of externalizing problems accounted for the longitudinal link between early trajectories of interparental conflict and children's social problems in preadolescence. PMID- 20576179 TI - Developmental cascades of peer relations and symptoms of externalizing and internalizing problems from kindergarten to fourth-grade elementary school. AB - A developmental cascade model linking symptoms of externalizing and internalizing psychopathology through three indices of peer relational difficulty (peer rejection, peer victimization, friendedness) was tested in a general population sample of 653 children followed annually from kindergarten to fourth grade. Rejection and victimization linked kindergarten externalizing problems with fourth-grade internalizing problems. Transactional links between rejection and victimization were found. In addition, peer rejection added to the development of externalizing problems. Friendedness did not add to the development of externalizing or internalizing problems. Cascade paths were similar for boys and girls. Over the period of kindergarten to fourth grade, psychopathology and peer relations become entangled, and the dynamic interplay between multiple manifestations of poor peer relations ultimately adds to the development of both externalizing and internalizing problems and their cross-time relation. Implications for research and prevention are discussed. PMID- 20576180 TI - Aggression, social competence, and academic achievement in Chinese children: a 5 year longitudinal study. AB - The primary purpose of this longitudinal study was to examine, in a sample of Chinese children (initial M age = 8 years, N = 1,140), contributions of aggression to the development of social competence and academic achievement. Five waves of panel data on aggression and social and school performance were collected from peer evaluations, teacher ratings, and school records in Grades 2 to 5. Structural equation modeling revealed that aggression had unique effects on later social competence and academic achievement after their stabilities were controlled, particularly in the junior grades. Aggression also had significant indirect effects on social and academic outcomes through multiple pathways. Social competence and academic achievement contributed to the development of each other, but not aggression. The results indicate cascade effects of aggression in Chinese children from a developmental perspective. PMID- 20576181 TI - Developmental cascades of peer rejection, social information processing biases, and aggression during middle childhood. AB - This study tested a developmental cascade model of peer rejection, social information processing (SIP), and aggression using data from 585 children assessed at 12 time points from kindergarten through Grade 3. Peer rejection had direct effects on subsequent SIP problems and aggression. SIP had direct effects on subsequent peer rejection and aggression. Aggression had direct effects on subsequent peer rejection. Each construct also had indirect effects on each of the other constructs. These findings advance the literature beyond a simple mediation approach by demonstrating how each construct effects changes in the others in a snowballing cycle over time. The progressions of SIP problems and aggression cascaded through lower liking, and both better SIP skills and lower aggression facilitated the progress of social preference. Findings are discussed in terms of the dynamic, developmental relations among social environments, cognitions, and behavioral adjustment. PMID- 20576182 TI - Cascading peer dynamics underlying the progression from problem behavior to violence in early to late adolescence. AB - This study examined the peer dynamics linking early adolescent problem behavior, school marginalization, and low academic performance to multiple indices of late adolescent violence (arrests, parent report, and youth report) in an ethnically diverse sample of 998 males and females. A cascade model was proposed in which early adolescent risk factors assessed at age 11 to 12 predict gang involvement at age 13 to 14, which in turn, predicts deviancy training with friends at age 16 to 17, which then predicts violence by age 18 to 19. Each construct in the model was assessed with multiple measures and methods. Structural equation modeling revealed that the cascade model fit the data well, with problem behavior, school marginalization, and low academic performance significantly predicting gang involvement 2 years later. Gang involvement, in turn, predicted deviancy training with a friend, which predicted violence. The best fitting model included an indirect and direct path between early adolescent gang involvement and later violence. These findings suggest the need to carefully consider peer clustering into gangs in efforts to prevent individual and aggregate levels of violence, especially in youths who may be disengaged, marginalized, or academically unsuccessful in the public school context. PMID- 20576183 TI - Psychopathology and social competence during the transition to adolescence: the role of family adversity and pubertal development. AB - This study examined developmental processes linking competence and psychopathology in an urban sample of girls during their transition to adolescence. Longitudinal associations among indices of externalizing symptoms, social competence, and internalizing symptoms were also tested within contexts of family adversity and girls' pubertal status. Child, parent, and teacher report were employed to assess core constructs across six annual assessment waves, starting at age 9. Results revealed the significant effect of prior levels of externalizing symptoms on changes in social competence and internalizing symptoms, as well as reciprocal relations between social competence and internalizing symptoms. In addition, girl's maladaptive functioning predicted increases in family adversity exposure over time. Last, more mature pubertal status in early assessment waves was linked to an increase in internalizing symptoms; however, this association was reversed by the last assessment, when most girls had reached advance stages of puberty. The timing of these effects reveals important targets for future interventions aimed at promoting the successful adaptation of girls in adolescence. PMID- 20576184 TI - Developmental cascades: externalizing, internalizing, and academic competence from middle childhood to early adolescence. AB - The current study was initiated to increase understanding of developmental cascades in childhood in a sample of at-risk boys (N = 291; 52% White). Mothers, teachers, and boys reported on boys' externalizing problems, internalizing difficulties, and academic competence. Consistent with hypotheses regarding school-related transitions, high levels of externalizing problems were associated with both low levels of academic competence and high levels of internalizing problems during the early school-age period, and with elevations in internalizing problems during the transition to adolescence. Low levels of academic competence were associated with high levels of internalizing problems in middle childhood, and with high levels of externalizing problems during the transition from elementary school to middle school. Shared risk factors played a minimal role in these developmental cascades. Results suggest that there are cascading effects of externalizing problems and academic competence in childhood and early adolescence, and that some cascading effects are more likely to occur during periods of school-related transitions. Implications of developmental cascade effects for research and intervention are discussed. PMID- 20576185 TI - Effects of childhood conduct problems and family adversity on health, health behaviors, and service use in early adulthood: tests of developmental pathways involving adolescent risk taking and depression. AB - This study examined a developmental, cascade model that includes childhood risks of conduct problems and family adversity at age 10-12; conduct problems, risk taking, and internalizing during adolescence; and adult outcomes of conduct problems, poor health, health risks, depression, and service use at ages 27 and 30. Analyses showed that childhood conduct problems predicted adolescent conduct problems and risk taking, which in turn, predicted adult conduct problems, health risks, depression, and service use. Childhood family adversity predicted adolescent internalizing, a predictor itself of poor health, depression, and service use at age 27. There was considerable continuity in the same adult outcomes measured over a 3-year period, as well as some cross-domain prediction from variables at age 27 to measures at age 30. Developmental patterns found in these data offer implications for future research and prevention. PMID- 20576186 TI - A cascade model connecting life stress to risk behavior among rural African American emerging adults. AB - A three-wave cascade model linking life stress to increases in risk behavior was tested with 347 African American emerging adults living in the rural South. Data analyses using structural equation modeling and latent growth curve modeling demonstrated that life stress was linked to increases in risk behavior as African Americans transitioned out of secondary school. The cascade model indicated that life stress fostered increases in negative emotions. Negative emotions, in turn, were linked to increases in affiliations with deviant peers and romantic partners; this forecast increases in risk behavior. The findings supported a stress proliferation framework, in which primary stressors affect increases in secondary stressors that carry forward to influence changes in risk behaviors that can potentially compromise mental health. PMID- 20576187 TI - The significance of childhood competence and problems for adult success in work: a developmental cascade analysis. AB - Success in the domain of work is a salient developmental task of adulthood and a key indicator of adaptive function in the evaluation of health and psychopathology. Yet few studies have examined pathways to work competence, especially with strategies testing for cumulative cascade effects over time. Cascade models spanning 20 years were tested via structural equation modeling, linking work competence in early adulthood to antecedent competence in work and other domains of competence in childhood and emerging adulthood. Data were drawn from the Project Competence longitudinal study of 205 school children followed for 20 years. Relative fit of alternative models was evaluated by the Bayesian information criterion. As hypothesized, the effectiveness of adaptive behavior in earlier age-salient developmental task domains forecasted later work competence, which also showed strong concurrent links to competence in other domains. Results suggest there are numerous pathways by which success or failure in major developmental task domains in childhood and adolescence may influence adaptation in other domains and eventually work competence, both concurrently and cumulatively over time. Cascade effects highlight the potential significance for later work competence of childhood conduct (antisocial vs. rule-abiding behavior) and social competence with peers, in addition to the ongoing role that academic attainment may have for work success. Work competence also showed considerable stability over a 10-year period during early adulthood. Implications and applications for future research and intervention are discussed. PMID- 20576189 TI - Extra-oral approach to removal of parotid duct stones. AB - There are many different management strategies for salivary calculi within the parotid ducts. Commonly, the stones can be extracted via an intra-oral approach. Stones that are farther from the papillae require more complex management. This article describes a technique for extra-oral excision of palpable salivary calculi using known external facial landmarks and dissection. Two cases are discussed and illustrations shown, and a brief discussion of other techniques for the management of salivary stones is included. PMID- 20576190 TI - Cooperation and conflict between very similar occupations: the case of anesthesia. AB - This article examines the features of a labor market in which there are two professional groups that both cooperate and directly compete with each other: certified registered nurse anesthetists (CRNAs) and anesthesiologists (MDAs). We examine how the relative numbers of these two types of anesthesia providers, and differences in regulation, affect the earnings of CRNAs, and the extent of supervision of CRNAs by MDAs. We find that both the earnings, and the likelihood of medical supervision of CRNAs, are closely determined by their market share. As the market share of CRNAs increases from 0% to 50%, the gains to MDAs from restricting competition increase; over this range the likelihood that CRNAs are supervised increases and their expected earnings decline. However, as the CRNAs' market share increases beyond 50%, the costs to MDAs of anticompetitive measures become too large, therefore, the probability of supervision declines, and the earnings of CRNAs increase. PMID- 20576188 TI - Evaluation of the interactionist model of socioeconomic status and problem behavior: a developmental cascade across generations. AB - The current multigenerational study evaluates the utility of the interactionist model of socioeconomic influence on human development (IMSI) in explaining problem behaviors across generations. The IMSI proposes that the association between socioeconomic status (SES) and human development involves a dynamic interplay that includes both social causation (SES influences human development) and social selection (individual characteristics affect SES). As part of the developmental cascade proposed by the IMSI, the findings from this investigation showed that Generation 1 (G1) adolescent problem behavior predicted later G1 SES, family stress, and parental emotional investments, as well as the next generation of children's problem behavior. These results are consistent with a social selection view. Consistent with the social causation perspective, we found a significant relation between G1 SES and family stress, and in turn, family stress predicted Generation 2 (G2) problem behavior. Finally, G1 adult SES predicted both material and emotional investments in the G2 child. In turn, emotional investments predicted G2 problem behavior, as did material investments. Some of the predicted pathways varied by G1 parent gender. The results are consistent with the view that processes of both social selection and social causation account for the association between SES and human development. PMID- 20576191 TI - Prevalence of anaemia among pregnant women in South-East China, 1993-2005. AB - OBJECTIVE: To report the prevalence of anaemia by demographic characteristics and its secular trend over 13 years for south-east Chinese pregnant women, and to determine the focus of anaemia prevention in Chinese pregnant women. DESIGN: Prospective study of the data on Hb concentration and other demographic information from a large-scale population-based perinatal health surveillance system in south-east China. SETTING: Fourteen cities or counties in Jiangsu and Zhejiang provinces. SUBJECTS: A total of 467 057 prenatal women who had participated in the perinatal health-care surveillance system and delivered babies from 1 January 1993 to 31 December 2005 and had a record of Hb in all three pregnancy trimesters. RESULTS: The overall prevalence of anaemia among pregnant women was 39.6 % from 1993 to 2005. Anaemia prevalence increased from the first (29.6 %) to the second (33.0 %) and third (56.2 %) trimesters. The prevalence of anaemia was higher in villagers, in women with less education and in women with higher gravidity or parity. The prevalence of anaemia in all of the trimesters was higher in the spring, summer and autumn and lower in the winter. The prevalence decreased from 1993 to 2005, from 53.3 % to 11.4 % for the first trimester, 45.6 % to 22.8 % for the second trimester and 64.6 % to 44.6 % for the third trimester. CONCLUSIONS: The prevalence of anaemia among pregnant women in Jiangsu and Zhejiang provinces decreased substantially from 1993 to 2005. However, anaemia in the third trimester is still a severe public health problem among pregnant women in these areas. PMID- 20576192 TI - Evaluating regional differences in breast-feeding in French maternity units: a multi-level approach. AB - OBJECTIVES: To study how individual and regional characteristics might explain regional variations in breast-feeding rates in maternity units and to identify outlier regions with very low or high breast-feeding rates. DESIGN: Individual characteristics (mother and infant) were collected during hospital stay. All newborns fed entirely or partly on breast milk were considered breast-fed. Regional characteristics were extracted from census data. Statistical analysis included multi-level models and estimation of empirical Bayes residuals to identify outlier regions. SETTING: All births in all administrative regions in France in 2003. SUBJECTS: A national representative sample of 13 186 live births. RESULTS: Breast-feeding rates in maternity units varied from 43 % to 80 % across regions. Differences in the distribution of individual characteristics accounted for 55 % of these variations. We identified two groups of regions with the lowest and highest breast-feeding rates, after adjusting for individual-level characteristics. In addition to maternal occupation and nationality, the social characteristics of regions, particularly the population's educational level and the percentage of non-French residents, were significantly associated with breast feeding rates. CONCLUSIONS: Social characteristics at both the individual and regional levels influence breast-feeding rates in maternity units. Promotion policies should be directed at specific regions, groups within the community and categories of mothers to reduce the gaps and increase the overall breast-feeding rate. PMID- 20576193 TI - Sociodemographic and lifestyle characteristics in relation to dietary patterns among young Brazilian adults. AB - OBJECTIVE: To identify dietary patterns among young adults and the relationships with socio-economic, demographic and lifestyle characteristics. DESIGN: Population-based, cross-sectional analysis of a cohort study. Food intake was assessed by a frequency questionnaire, and dietary patterns were identified using principal components analysis. SETTING: Southern Brazil. SUBJECTS: A total of 4202 men and women aged 23 years, who participated in the 1982 Pelotas Birth Cohort Study. RESULTS: Five dietary patterns were identified: common Brazilian, processed food, vegetable/fruit, dairy/dessert and tubers/pasta. Subjects who had low own or maternal educational levels, low social position or who were always poor throughout life had high adherence to the common Brazilian dietary pattern. In contrast, the processed food pattern was more likely to be followed by those belonging to middle and high social position and who were never poor. Men and smokers showed high adherence to the processed food and common Brazilian dietary patterns. Vegetable/fruit pattern was more likely to be followed by women and subjects engaged in physical activity. Women also showed high adherence to the dairy/dessert pattern. CONCLUSIONS: Our study among young Brazilian adults has identified distinct dietary patterns that are clearly influenced by socio economic and lifestyle characteristics, which have important policy implications in a country with marked social and economic inequalities. PMID- 20576194 TI - Fruit and vegetables should be targeted separately in health promotion programmes: differences in consumption levels, barriers, knowledge and stages of readiness for change. AB - OBJECTIVE: The aim of the present study was to investigate whether fruit and vegetables should be treated as separate groups in health promotion programmes by examining consumption levels, barriers, knowledge and the association between stage of change and potential predictors of fruit and vegetable intake. DESIGN: Computer-assisted telephone interview survey of the target population. SETTING: Hunter and New England regions of New South Wales, Australia. SUBJECTS: A total of 1403 parents and carers of primary-school-aged children. RESULTS: Consumption levels and knowledge of recommended intakes and serving size were greater for fruit than for vegetables. There were some differences in the main barriers to the consumption of fruit compared with those cited for vegetables. There was little congruence between the stages of change for fruit consumption and those for vegetable consumption. For fruit, knowledge of serving size and recommended intake, perceptions of adequate consumption, changes made to family intake and educational attainment were all correlated with stage of change categorisation. For vegetables, knowledge of recommended intake, perceptions of adequate consumption and changes made to family intake were correlated with stage of change categorisation. CONCLUSIONS: Significant differences in consumption levels, barriers, knowledge and stages of readiness for change can be shown when fruit and vegetables are treated as separate groups. Health promotion planners may need to consider interventions that focus on improving vegetable consumption in preference to fruit consumption. Messages about the recommended number of servings and serving size must be simplified and this may be achieved by targeting messages towards vegetable consumption. PMID- 20576195 TI - Development and evaluation of a method for calculating the Healthy Eating Index 2005 using the Nutrition Data System for Research. AB - OBJECTIVE: To develop and evaluate a method for calculating the Healthy Eating Index-2005 (HEI-2005) with the widely used Nutrition Data System for Research (NDSR) based on the method developed for use with the US Department of Agriculture's (USDA) Food and Nutrient Dietary Data System (FNDDS) and MyPyramid Equivalents Database (MPED). DESIGN: Cross-sectional. SETTING: Non institutionalized, community-dwelling adults aged 70 years and above. SUBJECTS: Two hundred and seventy-one adults participating in the Geisinger Rural Aging Study (GRAS) and 620 age- and race-matched adults from the National Health and Nutrition Examination Survey 2001-2002 (NHANES) were included in the analysis. The HEI-2005 scores were generated using NDSR in GRAS and compared to scores generated using FNDDS and MPED in NHANES. RESULTS: Similar total HEI-2005 scores (mean 62.0 (se 0.75) in GRAS v. 57.4 (se 0.55) in NHANES) were estimated, and the individual components most strongly correlated with total score in both samples were compared. Cronbach's coefficient alpha values of HEI-2005 were 0.52 in GRAS and 0.43 in NHANES. CONCLUSIONS: Since NDSR is commonly used for educational purposes, in clinical settings and in nutrition research, it is important to develop methodology for assessing diet quality through the use of HEI-2005 with this dietary analysis software application and its accompanying food and nutrient database. Results from the present study show that HEI-2005 scores can be generated with NDSR using the method described in the present study and the detailed USDA Center for Nutrition Policy and Promotion technical report as guidance. PMID- 20576196 TI - Breast-feeding in a complex emergency: four linked cross-sectional studies during the Bosnian conflict. AB - OBJECTIVE: To examine changes in breast-feeding and impacts on child health during the Bosnian conflict. DESIGN: Four linked representative cross-sectional household surveys, 1994 to 1997. SETTING: The countries of former Yugoslavia largely missed the international wave of enthusiasm for breast-feeding of the 1980s and early 1990s. The concern is that breast-feeding deteriorates during humanitarian emergencies, when children need it most. SUBJECTS: The four surveys visited a random sample of clusters from population registers in the Federation of Bosnia and Herzegovina (BiH) and the Republica Srpska (RS). Interviewers asked about breast-feeding and other factors related to child health, and measured mid upper-arm circumference in 1123 infants aged 1-12 months. RESULTS: One-fifth of infants were not breast-fed at all (220/1087). Muslim and displaced children were less likely to breast-feed; 59 % of Muslim displaced children never breast-fed. Among infants in sites visited by all four surveys, there was no change in the proportion ever breast-fed and a significant increase in duration of breast feeding and exclusive breast-feeding between 1994 and 1997. Children were breast fed for shorter durations in male absent households, in frontline communities, the RS, and households that did not receive remittances from abroad. Non-breast fed children and those who breast-fed for less than 4 months were more likely to be malnourished, as were those with complementary foods added either before or after their sixth month of life. CONCLUSIONS: If relief agencies had promoted and supported breast-feeding, this might have avoided some of the increased malnutrition that occurred during the conflict. PMID- 20576197 TI - Association between socio-economic status and childhood undernutrition in Bangladesh; a comparison of possession score and poverty index. AB - OBJECTIVE: To determine how much of the variation in nutritional status of Bangladeshi children under 5 years old can be attributed to the socio-economic status of the family. DESIGN: Nutritional status used reference Z-scores of weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height (WHZ). A 'possession score' was generated based on ownership of a radio, television, bicycle, motorcycle and telephone, and the availability of electricity, with categories of 0 to 4+ possessions. A five-point (quintile) 'poverty index' was created using principal component analysis. SETTING: The Bangladesh Demographic and Health Survey 2004 was the source of data. SUBJECTS: A sample of 4891 children aged <5 years was obtained. RESULTS: Some 57.8 % of the sample was either stunted, wasted or underweight (7.7 % were stunted, wasted and underweight). Of those stunted (48.4 %), 25.7 % were also underweight. Underweight and wasting prevalences were 40.7 % and 14.3 %, respectively. Mean WAZ, HAZ and WHZ did not differ by sex. Children of mothers with no education or no possessions were, on average, about 1 sd more underweight and stunted than those with higher educated mothers or with 4+ possessions. The possession score provided much greater discrimination of undernutrition than the poverty index. Nearly 50 % of children from households with no possessions were stunted, wasted or underweight (only 27 % in the poorest quintile), compared with only 3-6 % of children from households with 4+ possessions (over 13 % in the richest quintile). CONCLUSIONS: Maternal education and possession score were the main predictors of a child's nutritional status. Possession score was a much better indicator of undernutrition than the poverty index. PMID- 20576198 TI - Overall glycaemic index and glycaemic load of habitual diet and risk of heart disease. AB - OBJECTIVE: To test the hypothesis that diets with high glycaemic index (GI) and glycaemic load (GL) increase the risk of heart disease. DESIGN: Overall GI and GL were assessed from 7 d diet records or diet history interviews. SETTING: Information on hospitalization and death due to CVD and CHD was obtained from the National Register of Cause of Death and the National Register of Patients. SUBJECTS: In total 3959 adult Danes were - depending on time of entry - followed for 6-25 years until 31 December 1999. RESULTS: Overall GI was inversely associated with heart disease in men. The hazard ratios (95 % CI) for the 10th and 90th GI percentiles compared with the median were 1.38 (1.13, 1.68) and 0.90 (0.76, 1.07) for CVD morbidity, 1.45 (1.05, 1.99) and 0.81 (0.62, 1.06) for CVD mortality, and 1.31 (0.97, 1.76) and 0.65 (0.51, 0.84) for CHD morbidity. In male subjects GL was not associated with either outcome. In women no clear association between overall GI and heart disease was found, whereas positive non-linear associations were found for GL: at very high levels of GL, increase in GL was associated with increasing CVD and CHD morbidity. CONCLUSIONS: In men low-GI diets were associated increased risk of heart disease and GL was not associated with heart disease. In women there was no clear association between GI and heart disease, but to some extent a positive association between GL and heart disease was observed as hypothesized. PMID- 20576199 TI - Prevalence of breast-feeding in the Norwegian Mother and Child Cohort Study and health service-related correlates of cessation of full breast-feeding. AB - OBJECTIVE: First, to describe the prevalence of both full and partial breast feeding during the first 6 months; second, to study the associations between selected health service-related factors and cessation of full breast-feeding at three time intervals. DESIGN: Retrospective questionnaires, 6 months after birth. SETTING: The Norwegian Mother and Child Cohort Study (MoBa). SUBJECTS: In total, 29 621 women. RESULTS: While 96.6 %, 94.0 %, 90.8 %, 86.9 %, 83.8 % and 80.0 % of the infants were breast-fed at 1, 2, 3, 4, 5 and 6 months, respectively, the corresponding proportions for full breast-feeding were 84.6 %, 79.1 %, 70.9 %, 44.0 %, 16.7 % and 2.1 %. An increased risk of cessation of full breast-feeding during the first month was associated with supplementation during the first week of life with water (relative risk (RR) 1.77; 95 % CI 1.52, 2.06), sugar water (RR 1.73; 95 % CI 1.49, 2.00) or formula (RR 5.99; 95 % CI 5.58, 6.42). An increased risk was also associated with Caesarean delivery (RR 1.08; 95 % CI 1.00, 1.16) and breast-feeding problems (RR 1.56; 95 % CI 1.45, 1.67). Between months 1 and 3, the risk of cessation of full breast-feeding remained elevated in the case of supplementation during the first week of life with water (RR 1.29; 95 % CI 1.14, 1.45), sugar water (RR 1.48; 95 % CI 1.34, 1.64) or formula (RR 1.18; 95 % CI 1.07, 1.29). The same applied to Caesarean delivery (RR 1.15; 95 % CI 1.06, 1.25). CONCLUSIONS: Supplementation during the first week, breast-feeding problems and Caesarean delivery are associated with early cessation of full breast-feeding. The results support a cautious approach to supplementation during the first week of life. PMID- 20576200 TI - Serial cross-sectional analysis of prevalence of overweight and obese children between 1998 and 2003 in Leeds, UK, using routinely measured data. AB - OBJECTIVE: To monitor growth trends in young children in order to ascertain success (or otherwise) in halting the rapid rise in childhood obesity prevalence, and to assess the suitability of using routinely measured data for this purpose. DESIGN: Retrospective serial cross-sectional analyses of the proportion of obese children (logistic regression) and BMI standard deviation score (linear regression/maps) were undertaken. BMI coverage was calculated as percentage of sample with data ('usual'), percentage of total births and percentage of census values. BMI was standardised for age and sex (British reference data set). SETTING: Metropolitan Leeds, UK. SUBJECTS: Children aged 3 to 6 years. Weight, height, sex, age and postcode data were collected from Primary Care Trust records. RESULTS: Data were collected on 42 396 children, of whom 13 020 (31 %) were excluded due to missing data/data problems. Seventy-two per cent of 3-year olds and 92 % of 5-year-olds had data recorded ('usual' coverage). From 1998 to 2003 there was a significant increase in the proportion of obese children (4.5 % to 6.6 %; P < 0.001); children were 1.5 times more likely to be obese in 2003 than in 1998. CONCLUSIONS: Childhood obesity rose significantly between 1998 and 2003. Routinely measured data are an important means of monitoring population level obesity trends, although more effort is required to reduce the quantity of data-entry errors, for relatively low marginal cost. PMID- 20576201 TI - Socio-economic differences in eating-related attitudes, behaviours and environments of adolescents. AB - OBJECTIVE: The aim of the present study was to investigate the relationship between area-level socio-economic status and healthy and less healthy eating behaviours among adolescents and to determine whether the relationship between area-level socio-economic status and dietary behaviours was related to the relevant attitudes and environments. DESIGN: Data were collected as part of Youth'07, a nationally representative survey of the health and well-being of New Zealand youth. SETTING: New Zealand secondary schools, 2007. SUBJECTS: A total of 9107 secondary-school students in New Zealand. RESULTS: Students from more deprived areas perceived more supportive school environments and cared as much about healthy eating as students in more affluent areas. However, these students were significantly more likely to report consuming fast food, soft drinks and chocolates. CONCLUSIONS: Addressing area-level socio-economic disparities in healthy eating requires addressing the availability, affordability and marketing of unhealthy snack foods, particularly in economically deprived areas. PMID- 20576202 TI - Twenty-four-hour urinary water-soluble vitamin levels correlate with their intakes in free-living Japanese schoolchildren. AB - OBJECTIVE: To examine the association between 24 h urinary water-soluble vitamin levels and their intakes in free-living Japanese schoolchildren. DESIGN: All foods consumed for four consecutive days were recorded accurately by a weighed food record. A single 24 h urine sample was collected on the fourth day, and the urinary levels of water-soluble vitamins were measured. SETTING: An elementary school in Inazawa City, Japan. SUBJECTS: A total of 114 healthy, free-living, Japanese elementary-school children aged 10-12 years. RESULTS: The urinary level of each water-soluble vitamin was correlated positively to its mean intake in the past 2-4 d (vitamin B1: r = 0.42, P < 0.001; vitamin B2: r = 0.43, P < 0.001; vitamin B6: r = 0.49, P < 0.001; niacin: r = 0.32, P < 0.001; niacin equivalents: r = 0.32, P < 0.001; pantothenic acid: r = 0.32, P < 0.001; folic acid: r = 0.27, P < 0.01; vitamin C: r = 0.39, P < 0.001), except for vitamin B12 (r = 0.10, P = NS). Estimated mean intakes of water-soluble vitamins calculated using urinary levels and recovery rates were 97-102 % of their 3 d mean intake, except for vitamin B12 (79 %). CONCLUSIONS: The results show that urinary levels of water soluble vitamins, except for vitamin B12, reflected their recent intakes in free living Japanese schoolchildren and could be used as a potential biomarker to estimate mean vitamin intake. PMID- 20576203 TI - Role of selenium-containing proteins in T-cell and macrophage function. AB - Selenium (Se) has been known for many years to have played a role in boosting the immune function, but the manner in which this element acts at the molecular level in host defence and inflammatory diseases is poorly understood. To elucidate the role of Se-containing proteins in the immune function, we knocked out the expression of this protein class in T-cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T-cells manifested reduced pools of mature and functional T cells in lymphoid tissues and an impairment in T-cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T-cells led to an inability of these cells to suppress reactive oxygen species production, which in turn affected their ability to proliferate in response to T-cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in the immune function and tissue homeostasis. PMID- 20576204 TI - A rat model of mild intestinal inflammation induced by Staphylococcus aureus enterotoxin B. AB - The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration of Staphylococcus aureus enterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines. PMID- 20576205 TI - Immunology of pregnancy. AB - The conceptual framework for reproductive immunology was put in place over 50 years ago when the survival of the fetal semi-allograft within an immunocompetent mother was first considered. During this time, a number of paradigms have emerged and the mechanisms receiving current attention are those related to immune tolerance, such as regulatory T-cells and indoleamine 2,3,-dioxygenase, and innate immunity, such as natural killer cells, trophoblast debris and inflammation. A key consideration is the temporal and spatial variation in any of these pathways (e.g. implantation v. parturition). As fetally derived trophoblasts are the semi-allogeneic cells with which the maternal immune system comes into contact, understanding the immune response to these cells is critical. There is much interest in the immunological pathways that support a healthy pregnancy and how they might be perturbed in adverse pregnancy outcomes. Additionally, there is increasing awareness that antenatal determinants of the immune function of pregnant women and their offspring have consequences for health and disease in childhood and beyond. Changes in maternal diet over recent decades coincide with the increasing prevalence of allergic and other immune mediated diseases, and the modification of maternal diet has emerged as a strategy for disease prevention. Approaches undergoing trial at numerous sites around the world include dietary supplementation with fish oil and/or probiotics. Understanding the underlying mechanisms of any positive effect on disease outcomes should reveal further novel strategies for disease prevention. PMID- 20576206 TI - Ultrastructure of in vitro oocyte maturation in buffalo (Bubalus bubalis). AB - The objective of the present study was to describe ultrastructural changes in the nucleus and cytoplasmic organelles during in vitro maturation (IVM) of buffalo cumulus-oocyte complexes (COCs). The structures were collected by ovum pick-up (OPU). Some COCs, removed from maturation medium at 0, 6, 12, 18 and 24 h, were processed for transmission electron microscopy. The average number of COCs collected by OPU/animal/session was 6.4, and 44% of them were viable. Immature oocytes had a peripherally located nucleus, Golgi complex and mitochondrial clusters, as well as a large number of coalescent lipid vacuoles. After 6 h of IVM, the oocyte nucleus morphology changed from round to a flatter shape, and the granulosa cells (GC) lost most of their contact with zona pellucida (ZP). At 12 h the first polar body was extruded and the aspect of lipid droplet changed to dark, probably denoting lipid oxidation. Cortical granules were clearly visible at 18 h of maturation, always located along the oocyte periphery. At 24 h of IVM the number of cortical granules increased. Ultrastructure studies revealed that: (1) immature oocytes have a high lipid content; (2) the perivitelline space (PS) increases during IVM; (3) Golgi complexes and mitochondrial clusters migrate to oocyte periphery during IVM; (4) 6 h of IVM are enough to lose contact between GC and ZP; (5) the oocyte lipid droplets' appearance changes between 6 and 12 h of IVM. PMID- 20576207 TI - What can we learn from negative clinical trials in systemic sclerosis? PMID- 20576209 TI - Plasma endogenous enkephalin levels in early systemic sclerosis: clinical and laboratory associations. AB - OBJECTIVE: Met- and leu-enkephalins are endogenous opioid neuropeptides with potent analgesic, vasoactive, immunomodulatory and anti-apoptotic properties. We hypothesised that clinical or immunological variables of early systemic sclerosis (SSc) might be correlated to plasma enkephalin levels. METHODS: Plasma samples were collected at study entry of the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort (early SSc, n=116). Plasma met-enkephalin and leu enkephalin levels (microg/ml) were measured by high performance liquid chromatography (HPLC) and correlated to clinical and laboratory parameters in the GENISOS database. Statistical analyses were performed by nonparametric Wilcoxon rank sum tests and Pearson correlation coefficients. RESULTS: Significantly lower plasma met-enkephalin levels were associated with anti-topoisomerase-I seropositivity (6+8.3 vs. 14.9+22.8 microg/ml, p=0.02). Plasma leu-enkephalin levels were significantly higher in SSc patients with digital pulp loss (95.6+130 vs. 64.9+101 microg/ml, p=0.02). Lower mean plasma met-enkephalin levels and inversely higher leu-enkephalin levels were noted in SSc patients with Raynaud's phenomena (p=NS). CONCLUSION: The associations of plasma enkephalin levels to immunologic or clinical pathologies may underscore their vasogenic or fibrogenic significance and potential as therapeutic targets in early SSc. PMID- 20576210 TI - E/E' ratio is more sensitive than E/A ratio for detection of left ventricular diastolic dysfunction in patients with systemic sclerosis. AB - OBJECTIVES: To investigate the efficiency of early filling (E) and early diastolic mitral annular velocity (E') ratio (E/E' ratio) assessed by tissue Doppler imaging (TDI) on early detection of diastolic left ventricular (LV) dysfunction in systemic sclerosis (SSc) patients without congestive heart failure (CHF) symptoms. METHODS: Thirty-five Korean SSc patients without CHF symptoms and 35 healthy, age-sex matched controls were studied. Two-dimensional and M-mode echocardiography including conventional and tissue Doppler imaging was performed and pulmonary function test with diffusing capacity of lung for carbon monoxide was assessed. RESULTS: Mean E and late filling (A) ratio (E/A ratio) showed no significant difference between the two groups, while TDI showed that SSc patients had significantly elevated E/E' ratio (10.6+/-4.2 vs. 8.8+/-2.2, p=0.032), in comparison with controls. SSc patients who had taken angiotensin converting enzyme inhibitor or angiotensin II receptor blocker had significantly lower E/E' than those who had not (8.0+/-2.4 vs. 11.9+/-4.3, p=0.01). CONCLUSIONS: E/E' ratio is more sensitive than E/A ratio for identifying LV diastolic dysfunction in SSc patients without CHF symptoms. Furthermore, SSc patients who had received ACEI or ARB treatment showed significantly better preservation of LV diastolic function than those who had not received these medications. PMID- 20576211 TI - Reliability and validity of the delta finger-to-palm (FTP), a new measure of finger range of motion in systemic sclerosis. AB - OBJECTIVES: To determine the reliability and validity of a new measure of finger motion in patients with systemic sclerosis (SSc), the 'delta finger-topalm' (delta FTP) and compare its psychometric properties to the traditional measure of finger motion, the finger-topalm (FTP). METHODS: Phase 1: The reliability of the delta FTP and FTP were examined in 39 patients with SSc. Phase 2: Criterion and convergent construct validity of both measures were examined in 17 patients with SSc by comparing them to other clinical measures: Total Active Range of Motion (TAROM), Hand Mobility in Scleroderma (HAMIS), the Duruoz Hand Index (DHI), Health Assessment Questionnaire (HAQ), and modified Rodnan skin score (mRSS). Phase 3: Sensitivity to change of the delta FTP was investigated in 24 patients with early diffuse cutaneous SSc. RESULTS: Both measures had excellent intra rater and inter-rater reliability (ICC 0.92 to 0.99). Fair to strong correlations (rs=0.49-0.94) were observed between the delta FTP and TAROM, HAMIS, and DHI. Fair to moderate correlations were observed between delta FTP and HAQ components related to hand function and upper extremity mRSS. Correlations of the traditional FTP with these measures were fair to strong, but most often the delta FTP outperformed the FTP. The effect size and standardised response mean for the mean delta FTP were 0.50 and 1.10 respectively, over a 2-8 month period. CONCLUSIONS: The delta FTP is a valid and reliable measure of finger motion in patients with SSc which outperforms the FTP. PMID- 20576212 TI - Repeated teaching courses of the modified Rodnan skin score in systemic sclerosis. AB - OBJECTIVES: To evaluate the efficacy of a repeated teaching process of the modified Rodnan skin score (MRSS) in systemic sclerosis (SSc). The question is whether a repeated teaching course is required to maintain good results after a first, successful teaching process. METHODS: Two consecutive teaching courses were organised by two Romanian EUSTAR centres for the same rheumatologists, to evaluate and compare the inter-observer variability. Coefficients of variation, the intra-class correlation coefficients (ICC) and the within patient standard deviations were calculated. RESULTS: The ICC showed good agreement between 12 participants of both the first teaching course (0.639) and of the course seven months later (0.684). CONCLUSIONS: For rheumatologists, a good ICC that is close to 0.7 can be achieved, and these results remain stable without the need for another, repeated teaching cycle. The high inter-rater variations seen in some patients demand that, in clinical studies, the same investigator should assess the same patient at each visit. PMID- 20576213 TI - Screening and therapy for malnutrition and related gastro-intestinal disorders in systemic sclerosis: recommendations of a North American expert panel. AB - OBJECTIVES: To develop a set of recommendations for clinicians caring for patients with systemic sclerosis (SSc) to guide their approach to the patient with malnutrition and possible malabsorption. METHODS: The Canadian Scleroderma Research Group convened a meeting of experts in the areas of nutrition, speech pathology, oral health in SSc, SSc and gastroenterology to discuss the nutrition GI paradigm in SSc. This meeting generated a set of recommendations based on expert opinion. RESULTS: Physicians should screen ALL patients with SSc for malnutrition. The physician should ask a series of questions that pertain to GI involvement. Patients who screen positive for malnutrition should be referred to a dietitian and gastroenterologist. Referral to a patient support group should be considered and if screening reveals oral health problems, referral to a dentist, preferably with expertise in treating patients with SSc, should be done. All SSc patients should weigh themselves monthly and report any sudden significant changes in weight. They should be assessed by a rheumatologist once a year for signs of malnutrition. CONCLUSIONS: Malnutrition may be common in SSc and a multidisciplinary approach is important. PMID- 20576214 TI - Interactions between rheumatologists and cardio-/pulmonologists in the assessment and use of outcome measures in pulmonary arterial hypertension related to systemic sclerosis. AB - OBJECTIVES: Pulmonary arterial hypertension in patients with systemic sclerosis is a disease involving multiple organ systems. We investigated the differences in perceptions of how to measure PAH-SSc among cardiologists, pulmonologists and rheumatologists. We also examined how a Delphi exercise can improve agreement among these subspecialties. METHODS: The outcome measures derived from the recent Delphi survey were used for a detailed analysis of the contribution of the various specialties contributing to it. We compared rheumatologists and cardiologist/pulmonologists with regards to preferences and ratings of various endpoints and the actual use of tools to measure these outcomes. We also examined the effects of the Delphi process among these groups. RESULTS: We could show that the different expert groups each tended to contribute differently to the development of the core set of measures and that interactions in the Delphi process resulted in convergence of rankings. Despite agreement on the high importance of the domains in the Delphi, the use of tools within those domains was sometimes divergent and dependent on specialty. CONCLUSIONS: Based on these results, use of differing tools in the diagnosis and treatment of PAH-SSc can be anticipated. Further, the convergence of results provides evidence, for the first time, for the ability of various approaches in these disciplines to reach harmonious endpoints of care for PAHSSc patients. A collaborative, interdisciplinary approach is advantageous for PAH-SSc patients. PMID- 20576215 TI - Pulmonary arterial hypertension occurrence after liver transplant in systemic sclerosis: a report of 2 cases sustainably treated by sildenafil. AB - We present the unusual cases of 2 systemic sclerosis patients with a history of liver transplant, who developed pulmonary hypertension in the course of their diseases. Sildenafil was the preferred pulmonary arterial hypertension drug because of its safety within this context. Clinical and functional responses were good, with a follow-up of more than 2 years. PMID- 20576216 TI - Systemic sclerosis-associated interstitial lung disease-proposed recommendations for future randomized clinical trials. AB - Pulmonary disease is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). Recent well-designed trials in SSc-associated interstitial lung disease (SSc-ILD) have provided important insights regarding outcome measures and trial design. Recent investigations into the pathogenesis of SSc-ILD have led to a renewed interest in assessing targeted therapies in SSc ILD. With this in mind, we propose recommendations for the design of future SSc ILD studies in this review. PMID- 20576217 TI - Reversible posterior leukoencephalopathy in diffuse scleroderma. PMID- 20576218 TI - Biologic agents in rheumatology: act II. PMID- 20576219 TI - Development of TNF inhibitor therapies for the treatment of rheumatoid arthritis. AB - The recognition of tumor necrosis factor-alpha (TNF-alpha) as an important mediator of pathogenesis in rheumatoid arthritis (RA) led to the development of TNF inhibitors (TNFIs), which are a significant advance in the treatment of this debilitating disease. TNFIs revolutionized RA clinical practice, providing broader treatment options and establishing low disease activity and remission as achievable goals for many patients. Numerous clinical trials have shown that TNFIs are very effective, either as combination therapy or as monotherapy, in reducing the signs and symptoms of disease and slowing or inhibiting radiographic joint damage progression. Despite some adverse effects relating most frequently to infections and skin reactions, TNFIs are generally well tolerated in most patients and are widely recommended in clinical practice, in combination with good clinical judgment and individualized patient care. PMID- 20576220 TI - Impact of dosing on treatment with TNF inhibitors: managing dose adjustment. AB - The introduction of tumor necrosis factor (TNF) inhibitors for the treatment of rheumatoid arthritis (RA) represented a significant advance in the treatment of this debilitating disease, and led to dramatic changes in overall treatment goals and guidelines. Despite these advances, best practice use of TNF inhibitors in the clinical setting still needs to be determined. In particular, although all TNF inhibitors have standard, recommended doses that were determined in clinical trials, dose adjustments are often necessary in clinical practice to optimize therapeutic outcomes for individual patients. Dose escalation may be necessary in patients who experience disease flares, or because of insufficient initial efficacy or loss of efficacy over time, while dose tapering can be a response to adverse events, or if a patient achieves remission of disease. The amount of available evidence for managing dose adjustments for the currently available TNF inhibitors varies, and thus the strategies used with each are different. At present, although dose adjustments are common, data are insufficient for consensus guidelines to be recommended. PMID- 20576221 TI - The assessment of disease activity in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of diathrodial joints, with variable extra-articular manifestations. Joint damage begins early in the course of the disease as a consequence of the active inflammation, and can lead to progressive and irreversible disability. Successful treatment relies on patients attaining low disease activity or a state of remission, which have become achievable goals since the improved use of methotrexate (MTX) and the introduction of biological agents, especially tumor necrosis factor (TNF) inhibitors. To allow physicians to evaluate the indication and effect of particular therapies, accurate assessment of disease activity is necessary. Disease states in RA can be evaluated by a number of measures. These include signs and symptoms, such as counts of tender and swollen joints; laboratory measures like the acute phase response, which is a direct reflection of the underlying inflammatory activity; and patient-focused variables to measure pain and global assessment of disease activity. Some of these (and additional) measures are used in composite indices to assess disease activity or a disease activity state at any point in time and can inform the physician (and patient) about improvement (or deterioration) in disease activity from or states at a particular level at baseline, to that seen at any specific time point. The accurate assessment of disease is, therefore, an important part of the care of patients with RA. However, it can be complex to perform in the clinical setting, so new and simplified measures have evolved. Next to disease activity, the disease outcome is of utmost importance, in particular disability and quality of life, which are assessed using patient reported questionnaires. Radiographic assessment of structural changes is also an important outcome of RA and mirrors joint damage. The latest developments in the field are discussed and will help to identify patients who can benefit most from today's opportunities of pharmacotherapy, allowing optimization of patient care. PMID- 20576222 TI - The importance of the patients' experience of RA compared with clinical measures of disease activity. AB - Improvements in rheumatoid arthritis (RA) treatment have led to an increased focus on specialized and validated outcome measures, resulting in a decrease in the use of subjective assessments such as patient perceptions. However, to achieve optimal outcomes in the treatment of RA, there is a need to balance clinical goals with those that may be more important to patients. Although the treatment goals of physicians and patients are generally aligned, the framework in which these goals are expressed differs widely, and there are pronounced differences in how patients and physicians view their interactions regarding the decision-making process about treatment and information sharing. Detailed discussion between the physician and the patient regarding the patient's perspectives can lead to valuable insights into the patient's unmet needs from treatment as well as enhancement of the physician-patient relationship and an overall improvement in patients' quality of life. PMID- 20576223 TI - The impact of rheumatoid arthritis and treatment on patients' lives. AB - Rheumatoid arthritis (RA) is a chronic, debilitating disease that significantly impacts patients' quality of life and socioeconomic productivity. On a personal level, RA has a significant socioeconomic impact on patients' lives, being ranked among the highest of all chronic diseases for its effect on health-related quality of life (HRQoL), and limitations in physical function as well as increased pain and fatigue affect patients' attendance at paid work, their work performance within and outside the home, and their participation in family, social, and leisure activities. Additional paid or unpaid support, as well as increased flexibility and job modifications from employers, are often required so that patients can meet their role obligations. Disease-related reductions in work and household productivity are not just due to the physical limitations posed by RA; mental/emotional limitations also play a key role in reducing patients' HRQoL and productivity. Newer, effective treatments, such as tumor necrosis factor (TNF) inhibitors, improve the signs and symptoms of disease, inhibit progression of joint damage, and improve physical function and HRQoL. A recently available TNF inhibitor for RA, certolizumab pegol, has been shown to increase productivity outside and within the home and participation in family, social, and leisure activities as well as rapidly improve physical function, fatigue, and pain. Due to the importance of these parameters to patients, new therapies are increasingly assessed based on their ability to improve HRQoL, productivity, and participation. These extend the more traditional measures of efficacy into outcomes that are more central to patients' daily lives. PMID- 20576224 TI - Ultrasound Imaging for the rheumatologist XXVII. Sonographic assessment of the knee in patients with rheumatoid arthritis. AB - The aims of our study were to investigate the prevalence of ultrasound (US) pathologic abnormalities and to compare them with the clinical findings in the knee of rheumatoid arthritis (RA) patients. One hundred RA patients were enrolled in the study. Bilateral US examination of the knee was performed to visualise the presence of effusion, synovial proliferation, bone erosions, femoral cartilage abnormalities, quadricipital and/or patellar enthesopathy. The popliteal fossa and the calf region were also evacuate to detect popliteal cyst. We observed joint effusion in 140 out of 200 (70%) knees. Synovial hypertrophy was present in 115 out of 140 (82%) knees associated with effusion and in 22 out of 115 (19%) knees intra-articular power Doppler (PD) signal was found. Hyperechoic spots within the cartilage layer, suggestive of pyrophosphate crystals deposit, were detected in the knees of 3 patients. US signs of quadricipital and/or patellar enthesopathy were detected in 53 out 200 (26%) knees. Bone erosions were visualised in 16 out 200 (8%) knees. Popliteal cyst was found in 66 out of 200 (33%) joints. US examination of the knee is more sensitive than clinical examination in the detection of joint inflammation and allows for the identification of different patterns of pathologic changes at knee level, including morphostructural changes at both cartilage and tendon level. PMID- 20576225 TI - Clinical application of the CASPAR criteria for psoriatic arthritis compared to other existing criteria. AB - OBJECTIVES: Psoriatic arthritis (PsA) has been defined as a systemic, chronic, inflammatory arthritis, usually seronegative for rheumatoid factor (RF), associated with cutaneous psoriasis. The exact prevalence of PsA is unknown and its estimation has been difficult, partly due to the lack of a widely accepted classification criteria. Agreed and validated criteria will facilitate comparison between centres and different countries in the areas of epidemiology, outcome studies and therapeutic trials. A number of classification criteria have been published by Moll & Wright (M & W), Bennett's, Vasey and Espinoza (V & E), Fournie's, European Spondyloarthropathy Study Group (ESSG), McGonagle, Gladman and most recently, the CASPAR Study Group. In this paper, we present an audit aiming to assess which of these criteria performs better in clinical practice. METHODS: Sixty-nine (69) patients with evidence of PsA were seen in the clinic as regular outpatients and were assessed as to whether they fulfil any of the 6 existing criteria for PsA: M & W, Bennett's, V & E, Fournie's, ESSG and CASPAR criteria. All items included in the 6 sets of criteria were recorded for each patient based on interview, clinical examination and scrutiny of clinical medical records. By comparing the criteria between themselves as well as the items used in each one of them we tried to assess which one of the criteria was performing best. RESULTS: A total of 69 patients (M/F=24/45; mean age 46.4 years (+/-20.3), and delay in diagnosis of 3.4 years (+/-4.1) was assessed. From those, 9 patients did not fulfil any criteria and excluded from the analysis. From the remaining 60 patients [M/F=21/39; (age 48+/-15.3)], 21 patients (35%) fulfilled all 6 sets of criteria. The remaining 39 patients (M/F=41/59 %; age 47+/-14.9) were further analysed with regards to the feature that did not enable concordance. From those 39 patients, Bennett's criteria were positive in only 4/39 (10.2%), M & W criteria were positive in 12/39 (30.7%), ESSG criteria in 17/39 (43.5%), V & E criteria were positive in 18/39 (46.1%), Fournie's criteria were positive in 31/39 (79.4%) and CASPAR criteria in 35/39 (89.7%). By including family history of psoriasis in the criteria, 11/39 patients (28.2%), who did not fulfil M & W or V & E due to lack of family history of psoriasis as item, met the CASPAR criteria. In addition, some patients who did not fulfil the M & W criteria, since RF positive (7/39; 17.9%), were able to satisfy the CASPAR criteria. CONCLUSIONS: Family history of psoriasis is the main advantage of the new CASPAR Criteria over M & W and V & E. In addition, using the CASPAR criteria, it is possible to make a diagnosis of PsA in a patient who develops inflammatory articular disease even if with RF positive and polyarticular symmetrical arthritis. It is also important to have these classification criteria for the development of recommendations for the optimal treatment of patients with PsA. We believe that the CASPAR criteria, which are simple and easy to use, have high potential to be introduced as the universal classification criteria for PsA. However, further study of the validation of these new criteria is required. PMID- 20576226 TI - IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. AB - OBJECTIVES: The genetic control of Interleukin-10 (IL-10) and Tumour necrosis factor-alpha (TNF-alpha) production and the possible interaction between the two cytokines in influencing SLE susceptibility as well as clinical features has not been completely evaluated in the Taiwanese population. METHODS: We investigated the association of IL-10 and TNF-alpha promoter polymorphisms (-1082, -819 and 592 for IL-10 gene; -308 for TNF-alpha gene) with SLE in a total of 172 Taiwanese patients and 215 controls. RESULTS: Our results indicate that IL-10 A/T/A-A/T/A genotype was associated with Taiwanese SLE, whereas no significance was observed between TNF-alpha genotype and SLE. Furthermore, the TNF-alpha G allele frequency of the polymorphism at -308 was significantly decreased in patients with oral ulcers. The combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly increased in SLE patients. In addition, the combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly decreased in patients with oral ulcers. CONCLUSIONS: These results suggest a significant correlation of the combined IL-10 and TNF-alpha genetic polymorphisms contribute to SLE susceptibility and clinical features in the Taiwanese population. PMID- 20576227 TI - Exacerbation of psoriatic skin lesions in patients with psoriatic arthritis receiving anti-tumour necrosis factor-alpha therapy: description of 3 cases and review of the literature. AB - The use of tumour necrosis factor alpha (TNF-alpha) blockade to treat patients with both psoriasis and psoriatic arthritis (PsA) is now well established. However, paradoxical case reports of new-onset or exacerbation of psoriasis during all TNF-alpha blockers therapy have been published. We now review the literature and add a description of three PsA patients whose arthritis had responded well to TNF blockade but in whom major exacerbation of their psoriatic skin lesions occurred. PMID- 20576228 TI - Pseudo-septic hip arthritis as the presenting symptom of ankylosing spondylitis: a case series and review of the literature. AB - INTRODUCTION: Ankylosing spondylitis (AS) typically presents with inflammatory back pain and stiffness, but severe hip involvement may also be present. In this study, we evaluated the frequency of severe hip arthritis mimicking septic arthritis as initial presenting symptom of AS. METHODS: Utilising billing records, we retrospectively studied all AS patients seen from the years 2006 to 2009 at our institution. The primary endpoint was severe hip arthritis mimicking septic arthritis as the initial presenting symptom of AS. RESULTS: A total of 121 AS patients were identified from billing records, of whom 3 had severe hip arthritis mimicking septic arthritis as the initial presenting symptom of ankylosing spondylitis. CONCLUSIONS: Our study highlights the importance of including AS in the differential diagnosis of severe acute inflammatory hip arthritis in young adults, even when the onset appears to be abrupt. PMID- 20576229 TI - Sicca syndrome and salivary gland infiltration in children with autoimmune disorders: when can we diagnose Sjogren syndrome? AB - OBJECTIVES: To analyse the initial presentation and outcome of children with a diagnosis of childhood-onset Sjogren's syndrome (SS) in a paediatric referral care center. To study whether the diagnosis was made in accordance with the most recent criteria of paediatric SS and to compare our patients to those reported in the literature. METHODS: We retrospectively analysed the clinical, histological and laboratory features of patients seen over a period of 15 years and diagnosed with SS before the age of 16. RESULTS: Eight patients had a diagnosis of SS in childhood and were followed for up to 14 years. Diagnosis of SS was based on histological evidence of salivary gland involvement in all patients with or without presence of specific autoantibodies (anti-SSA and -SSB). Sicca syndrome as a presenting symptom occurred in only 2/8 of children, recurrent parotid swelling in 3/8; whereas anti-SSA/SSB antibodies and typical salivary-gland histology were found in 6/8 patients. Five children fulfilled the proposed paediatric criteria for SS. Three patients did not fulfill the paediatric criteria but disclosed typical histology findings. Two patients developed overlapping lupus nephritis or autoimmune hepatitis years following diagnosis of SS. CONCLUSIONS: Childhood-onset SS is an heterogeneous disease in its presentation and outcome. The diagnosis may be discussed in some patients who do not fulfill the proposed diagnosis criteria, even though they disclose sicca syndrome and typical immunologic and histological findings. Some patients with typical SS may develop overlapping lupus disease over time. PMID- 20576230 TI - Infliximab in a patient with ankylosing spondylitis and secondary IgA nephropathy requiring haemodialysis. PMID- 20576231 TI - Gonad evaluation in male dermatomyositis. A pilot study. PMID- 20576233 TI - Acute renal failure after intravenous immunoglobulin therapy. PMID- 20576232 TI - Successful adalimumab treatment of HLA B27 negative heel enthesitis documented with MRI and US. PMID- 20576234 TI - Prompt efficacy of plasmapheresis in a patient with systemic lupus erythematosus and diffuse alveolar haemorrhage. PMID- 20576236 TI - Transmissibility of 2009 pandemic influenza A(H1N1) in New Zealand: effective reproduction number and influence of age, ethnicity and importations. AB - The first wave of pandemic influenza A(H1N1) has subsided in New Zealand as in other southern hemisphere countries. This study aimed to estimate the effective reproduction number (R) of 2009 pandemic influenza A(H1N1) taking into account imported cases. It also aimed to show the temporal variation of R throughout the New Zealand epidemic, changes in age- and ethnicity-specific cumulative incidence, and the effect of school holidays. Using a new modelling method to account for imported cases, we have calculated the peak R during the containment phase of the pandemic as 1.55 (95% confidence interval: 1.16 to 1.86). This value is less than previously estimated in the country early in the pandemic but in line with more recent estimates in other parts of the world. Results also indicated an increase in the proportion of notifications among school-age children after the school holiday (3-19 July 2009). This finding provides support for the potential effectiveness of timely school closures, although such disruptive interventions need to be balanced against the severity of the pandemic. PMID- 20576237 TI - 2009 pandemic influenza A(H1N1) virus in Scotland: geographically variable immunity in Spring 2010, following the winter outbreak. AB - We determined the age- and location-specific seroprevalence of antibodies against 2009 pandemic influenza A(H1N1) virus in Scotland following the first two waves of infection. Serum samples collected following the winter outbreak were analysed by microneutralisation assay. The proportion of positive sera varied significantly between cities and, in the case of Inverness, between age groups (with younger adults more likely to be positive than older individuals). This study demonstrates that older people are no longer more likely to have antibodies against the virus than younger adults. PMID- 20576235 TI - Using tests for recent infection to estimate incidence: problems and prospects for HIV. AB - Tests for recent infection (TRIs), such as the BED assay, provide a convenient way to estimate HIV incidence rates from cross-sectional survey data. Controversy has arisen over how the imperfect performance of a TRI should be characterised and taken into account. Recent theoretical work is providing a unified framework within which to work with a variety of TRI- and epidemic-specific assumptions in order to estimate incidence using imperfect TRIs, but suggests that larger survey sample sizes will be required than previously thought. This paper reviews the framework qualitatively and provides examples of estimator performance, identifying the characteristics required by a TRI to estimate incidence reliably that should guide the future development of TRIs. PMID- 20576238 TI - Nationwide outbreak of Salmonella enterica serotype 4,12:i:- infections in France, linked to dried pork sausage, March-May 2010. AB - In May 2010, a nationwide excess of infections with the specific monophasic variant Salmonella enterica serotype 4,12:i:- was investigated in France. Subtyping with multilocus variable number of tandem repeats analysis revealed a distinct epidemic strain within this excess. Epidemiological investigations identified a dried pork sausage sold by a particular chain of supermarkets as the likely vehicle of transmission. The suspected batches have been withdrawn and recalled. PMID- 20576243 TI - Healthy home/healthy life. PMID- 20576244 TI - Optical coherence tomography is a viable instrument to quantitatively and qualitatively distinguish optic disc edema from optic nerve drusen. PMID- 20576245 TI - How do visual and cognitive impairments affect health-related quality of life in nursing home residents? PMID- 20576247 TI - Nutrition counseling in the optometric practice. AB - The AOA Optometric Clinical Practice Guidelines on Care of the Patient with Age Related Macular Degeneration now recommend optometrists counsel patients on the importance of proper nutrition,in line with the findings of the Age-Related Eye Disease Study (AREDS).Here is how optometrists can effectively counsel patients on the benefits of good nutrition for eye health. PMID- 20576248 TI - What eye care patients should know about nutrition. AB - Research has identified 6 nutrients that promote healthy vision and may reduce the risk of eye diseases. Sufficient quantities of these nutrients are generally not obtained through a normal diet.Nutritional supplements are an easy way to obtain the recommended levels. PMID- 20576249 TI - Macular pigment and healthy vision. AB - A growing body of evidence has established a link between lutein and zeaxanthin,higher levels of MPOD, increased visual performance, and decreased risk for AMD and other age-related eye diseases.A number of findings suggest that MPOD measurement may be a reliable tool to identify individuals at risk for or experiencing early-stage AMD. Devices are commercially available to measure MPOD and new objective technologies are emerging. PMID- 20576250 TI - Information on nutrition and eye health. AB - New American Optometric Association materials can assist optometrists in helping patients understand the importance of good nutrition. A growing number of Web based services offers nutrition information that may be interesting to both patients and practitioners. PMID- 20576251 TI - Positioning the optometric practice in the eye care market. AB - Appropriate marketing is essential as optometric practices continue to grow as providers of eye and vision care. PMID- 20576252 TI - [Sarcoidosis in the nasopharynx, a rare location]. AB - Sarcoidosis is a systemic granulomatous disease that usually has a pulmonary presentation. The extrapulmonary organs most frequently affected are lymph nodes, eyes and skin. Rhinopharyngeal involvement is extremely rare. We describe a case of sarcoidosis which was diagnosed through its location in the nasopharynx. PMID- 20576254 TI - Complex atypical hyperplasia of the uterus: characteristics and prediction of underlying carcinoma risk. AB - OBJECTIVE: The objective of the study was to identify additional factors that may improve the ability to predict underlying carcinoma risk in patients with complex atypical hyperplasia (CAH) of the uterus. STUDY DESIGN: All subjects diagnosed with CAH of the uterus on endometrial sampling from March 1994 to May 2008 were identified. CAH was classified as CAH suspicious, CAH polypoid, CAH focal, or CAH not otherwise specified (NOS). Subjects were then exclusively assigned to 1 of 3 categories: CAH suspicious, CAH NOS, or CAH focal and/or polypoid. RESULTS: We identified 197 cases of CAH diagnosed on preoperative endometrial sampling. Carcinoma was subsequently diagnosed in the hysterectomy specimen in 67 subjects (34%). The risk of underlying carcinoma if assigning subjects as CAH suspicious, CAH NOS, or CAH polypoid and/or focal was 56%, 36%, and 20%, respectively (P < .001). CONCLUSION: The risk of underlying carcinoma in patients with CAH on preoperative endometrial sampling is associated with the method of sampling and age and can be significantly modified by the nature of pathologic assessment. PMID- 20576255 TI - Estimation of the cortical functional connectivity by directed transfer function during mental fatigue. AB - In this paper, the directed transfer function (DTF) method is used to characterize changes in the functional coupling of EEG rhythms in different brain cortical areas due to the mental fatigue caused by long-term cognitive tasks. There is a parietal-to-frontal functional coupling of the total (0.5-30 Hz) EEG frequency band in the right and middle brain cortical areas during the pre-task period, and an inversion of that direction, even a significant prevalence of the frontal-to-parietal direction, after the completion of the task. When mental fatigue levels increase, the parietal-to-frontal functional coupling of the alpha (8-12 Hz) frequency band is weakened, and the beta (13-30 Hz) frequency band changes from a balanced directionality of the functional cortical coupling to frontal-to-parietal functional coupling, whereas the frontal-to-center functional coupling of the total frequency band is enhanced in the right hemisphere, and the frontal-to-center functional coupling of the beta frequency band is heightened in the left hemisphere. Meanwhile, in the central cortical area, the middle-to-left functional coupling of the total, beta and alpha frequency bands increases significantly and the middle-to-right functional coupling of the total and beta frequency bands increases significantly after the task as compared to the pre task period. These findings suggest that the functional coupling of the frontal, central and parietal brain cortical areas is strongly correlated with a change in mental fatigue levels in the wake-fatigue transition. The experimental results indicate that the DTF method can effectively explore the change of the direction and strength of the information flow underlying cortical-to-cortical functional coupling when mental fatigue is increased by long-term cognitive work. The DTF method may open a promising way to study mental fatigue. PMID- 20576253 TI - Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis. AB - OBJECTIVE: To assess the accuracy of transvaginal sonographic cervical length (CL) in predicting spontaneous preterm birth in women with twin pregnancies. STUDY DESIGN: Systematic review and metaanalysis of predictive test accuracy. RESULTS: Twenty-one studies (16 in asymptomatic women and 5 in symptomatic women) with a total of 3523 women met the inclusion criteria. Among asymptomatic women, a CL n)-linked disaccharides with n=1, 2, 3, or 4) or by two stable (comparably populated and differing in the third glycosidic dihedral angle omega ; gg or gt) states with a low interconversion barrier ((1- >6)-linked disaccharides). Metastable (anti-phi or anti-psi) states are also identified with relative free energies in the range of 8-22 kJ mol(-1). The 11 compounds can be classified into four families: (i) the alpha(1-->1)alpha-linked disaccharide trehalose (axial-axial linkage) presents no metastable state, the lowest configurational entropy, and no intramolecular H-bonds; (ii) the four alpha(1-->n)-linked disaccharides (n=1, 2, 3, or 4; axial-equatorial linkage) present one metastable (anti-psi) state, an intermediate configurational entropy, and two alternative intramolecular H-bonds; (iii) the four beta(1-->n)-linked disaccharides (n=1, 2, 3, or 4; equatorial-equatorial linkage) present two metastable (anti-phi and anti-psi) states, an intermediate configurational entropy, and one intramolecular H-bond; (iv) the two (1-->6)-linked disaccharides (additional glycosidic dihedral angle) present no (isomaltose) or a pair of (gentiobiose) metastable (anti-phi) states, the highest configurational entropy, and no intramolecular H-bonds. The observed conformational preferences appear to be dictated by four main driving forces (ring conformational preferences, exo anomeric effect, steric constraints, and possible presence of a third glycosidic dihedral angle), leaving a secondary role to intramolecular H-bonding and specific solvation effects. In spite of the weak conformational driving force attributed to solvent-exposed H-bonds in water (highly polar protic solvent), intramolecular H-bonds may still have a significant influence on the physico chemical properties of the disaccharide by decreasing its hydrophilicity. Along with previous work, the results also complete the suggestion of a spectrum of approximate transition timescales for carbohydrates up to the disaccharide level, namely: approximately 30 ps (hydroxyl groups), approximately 1 ns (free lactol group, free hydroxymethyl groups, glycosidic dihedral angleomega in (1-->6) linked disaccharides), approximately 10 ns to 2 micros (ring conformation, glycosidic dihedral angles phi and psi). The calculated average values of the glycosidic torsional angles agree well with the available experimental data, providing validation for the force-field and simulation methodology employed. PMID- 20576259 TI - Time series analysis on the health effects of temperature: advancements and limitations. AB - The association between extreme temperatures and health outcomes has been frequently investigated during the last few years. This assessment is usually based on a time series design, a framework which has gained a substantial development in the last two decades. In this contribution we offer an overview of the recent methodological advancements which provide new statistical tools to examine the health effects of temperature in a time series setting, highlighting at the same time the main limitations that still affect this research area. PMID- 20576258 TI - Frontal lobe damage impairs process and content in semantic memory: evidence from category-specific effects in progressive non-fluent aphasia. AB - Portions of left inferior frontal cortex have been linked to semantic memory both in terms of the content of conceptual representation (e.g., motor aspects in an embodied semantics framework) and the cognitive processes used to access these representations (e.g., response selection). Progressive non-fluent aphasia (PNFA) is a neurodegenerative condition characterized by progressive atrophy of left inferior frontal cortex. PNFA can, therefore, provide a lesion model for examining the impact of frontal lobe damage on semantic processing and content. In the current study we examined picture naming in a cohort of PNFA patients across a variety of semantic categories. An embodied approach to semantic memory holds that sensorimotor features such as self-initiated action may assume differential importance for the representation of manufactured artifacts (e.g., naming hand tools). Embodiment theories might therefore predict that patients with frontal damage would be differentially impaired on manufactured artifacts relative to natural kinds, and this prediction was borne out. We also examined patterns of naming errors across a wide range of semantic categories and found that naming error distributions were heterogeneous. Although PNFA patients performed worse overall on naming manufactured artifacts, there was no reliable relationship between anomia and manipulability across semantic categories. These results add to a growing body of research arguing against a purely sensorimotor account of semantic memory, suggesting instead a more nuanced balance of process and content in how the brain represents conceptual knowledge. PMID- 20576260 TI - The recurrence interval of forest fires in Cabeco da Vaca (Cabreira Mountain- northwest of Portugal). AB - The recurrence of forest fires is degrading an important part of the Portuguese natural heritage namely its forest and soils. In this paper we present the case study of Cabeco da Vaca (Cabreira Mountain-northwest Portugal), where in recent decades, particularly in the 70s, there was a significant increase in the number of forest fires and in the areas scorched annually. There is thus a turning point between a period when fire was an integral part of the ecosystems and when fire has become a serious threat to woodland management and development (Bento Goncalves, 2006). Starting with a thorough characterization of forest fires and based on the mapping of scorched areas between 1990 and 2006, we have proceeded to identify the annual pattern of maximum recurrence and the definition of the return interval in Cabeco da Vaca, producing thus a valuable document to support management and forestry development in general. PMID- 20576261 TI - No relationship between the type of pituitary suppression for IVF and chromosomal abnormality rates of blastomeres: an observational study. AB - OBJECTIVE: To investigate whether the incidence of chromosomally abnormal blastomeres is related to the type of pituitary suppression used in ovarian stimulation. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENT(S): The study involved 694 consecutive cycles; 320 belonged to agonist group and 374 to antagonist group, of patients' <= 37 years of age who underwent preimplantation genetic screening between October 1, 1992 until December 31, 2006. All of them (and their partners) had normal karyotyping results. Only the data of patients who had at least one embryo biopsy were analyzed. INTERVENTION(S): Preimplantation genetic screening (PGS). MAIN OUTCOME MEASURE(S): The primary outcome measure was detection of abnormal blastomeres on the total number of embryos analyzed. RESULT(S): The total abnormal ratio was statistically similar between the embryos of the two study groups (49.9 +/- 28.1 vs. 50.2 +/- 26.6). Likewise, a multivariate (linear regression) analysis indicated that the total abnormality ratio was not influenced by the type of stimulation when simultaneously adjusting for age, rank of trials, indication for preimplantation genetic screening, total gonadotropin amount, number of cumulus oocyte complexes, and number of two pronuclear oocytes embryos. No difference was observed in ongoing pregnancy rates between agonists and antagonists (26.6% vs. 23.3%, respectively). CONCLUSION(S): Based on our findings there is no difference in the proportion of abnormal blastomeres either when using gonadotropin releasing hormone (GnRH) agonist, or antagonist protocol. PMID- 20576262 TI - A systematic review of the effect of the distension medium on pain during outpatient hysteroscopy. AB - OBJECTIVE: To assess the effect of distension medium on pain during outpatient hysteroscopy. DESIGN: Systematic review and meta-analysis. SETTING: Outpatient hysteroscopy clinics. PATIENT(S): Women undergoing outpatient hysteroscopic examination. INTERVENTION(S): Use of normal saline versus carbon dioxide as distension medium for outpatient hysteroscopy. MAIN OUTCOME MEASURE(S): Pain scores. RESULT(S): There was no statistically significant difference in pain scores when carbon dioxide or normal saline were used as the distension medium for outpatient hysteroscopy (standardized mean differences=-0.05; 95% CI, -0.17 to 0.07; I2=92%). CONCLUSION(S): Carbon dioxide and normal saline are both suitable distending media for outpatient hysteroscopy as the procedural pain is comparable and the views obtained are satisfactory. However, normal saline does confer advantages that may make it more suitable for clinical use. PMID- 20576263 TI - Heterotopic pregnancy: it is really a rare event? The importance to exclude it not only after in vitro fertilization but also in case of spontaneous conception. PMID- 20576264 TI - State laws and regulations addressing third-party reimbursement for infertility treatment: implications for cancer survivors. AB - OBJECTIVE: To examine codified state policies related to infertility and assess their implications for cancer patients. Lack of insurance is often identified as a barrier to use of fertility preservation (FP) services. DESIGN: None. SETTING: A keyword search was developed to identify statutes and administrative regulations of insurance coverage for FP in the United States. PATIENT(S): N/A. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Laws addressing the general population but pertaining to FP were compiled using Lexis-Nexis. Data were analyzed by reviewing the "plain meaning" of the text, legislative/administrative history, and annotated case law. Legal reasoning and common rules of statutory construction and legislative interpretation were used. RESULT(S): Fifteen states (29.4%) had laws relating to insurance coverage for infertility or in vitro fertilization (IVF) procedures and two states (CA and IL) specifically excluded IVF from a mandatory offer of coverage. No state laws or regulations addressed insurance coverage for FP methods specific to cancer patients. CONCLUSION(S): There is an argument for policies that require coverage for FP for cancer survivors before treatment. PMID- 20576266 TI - Implanon use lowers plasma concentrations of high-molecular-weight adiponectin. AB - OBJECTIVE: To investigate the effect of the low-dosed etonogestrel-releasing contraceptive implant Implanon on new cardiovascular risk markers, we studied the effect of this implant on adiponectin and its metabolically important isomer high molecular-weight adiponectin (HMW). Low-dosed progestagen-only contraception is preferentially prescribed to females with increased cardiovascular risks. DESIGN: Longitudinal study. SETTING: Family-planning center of a university hospital. PATIENT(S): Forty healthy nonsmoking women with regular cycles (n=20 controls without hormonal contraception; n=20 cases wishing the insertion of Implanon). INTERVENTION(S): Blood samples for the measurements of adiponectin, HMW, C reactive protein (CRP), sex hormone binding globulin, sexual hormones, and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle four. MAIN OUTCOME MEASURE(S): At baseline there was a significant correlation between adiponectin and the parameters hsCRP and high-density lipoprotein. Implanon treatment caused a significant decrease in HMW and the HMW/adiponectin ratio. Additionally plasma lipids (cholesterol, high-density lipoprotein, low-density lipoprotein), sex hormone binding globulin, and testosterone levels decreased significantly. Adiponectin plasma concentrations were not affected. CONCLUSION(S): Short-term Implanon use in healthy premenopausal women was associated with a decrease in the cardioprotective adiponectin isomer HMW. It remains to be investigated if this decrease persists after longer use of the implant. PMID- 20576267 TI - Bone marrow transplantation in mice as a tool for studying the role of hematopoietic cells in metabolic and cardiovascular diseases. AB - Hematopoietic cells have been established as major players in cardiovascular disease, with an important role in the etiology of atherosclerotic plaque. In addition, hematopoietic cells, and in particular the cells of monocyte and macrophage lineages, have recently been unmasked as one of the main causes of metabolic abnormalities leading to insulin resistance and type 2 diabetes. With the availability of transgenic mouse models that reproduce many aspects of these diseases, research in these areas has been able to make exceptional progress. Much of the work exploring the role of hematopoietic cells has been carried out on chimeric mice made by the recipient disease model mice being given donor bone marrow cells from transgenic mice harboring a genetic alteration in a relevant pathway. Here, we will describe the potential of the bone marrow transplantation approach and discuss recent developments, including the use of virally transduced cells. We will explain some of the caveats, their effect on the experimental outcomes, and some possible solutions. Taken as a whole, this technology offers great advantages in efficiency and cost-effectiveness, and it is expected to continue to be a crucial technique in cardiovascular research work. PMID- 20576268 TI - Muscle mass in musculoskeletal models. AB - Most current models of musculoskeletal dynamics lump a muscle's mass with its body segment, and then simulate the dynamics of these body segments connected by joints. As shown here, this popular approach leads to errors in the system's inertia matrix and hence in all aspects of the dynamics. Two simplified mathematical models were created to capture the relevant features of monoarticular and biarticular muscles, and the errors were analyzed. The models were also applied to two physiological examples: the triceps surae muscles that plantar flex the human ankle and the biceps femoris posterior muscle of the rat hind limb. The analysis of errors due to lumping showed that these errors can be large. Although the errors can be reduced in some postures, they cannot be easily eliminated in models that use segment lumping. Some options for addressing these errors are discussed. PMID- 20576269 TI - Monoliths from poly(ethylene glycol) diacrylate and dimethacrylate for capillary hydrophobic interaction chromatography of proteins. AB - Rigid monoliths were synthesized solely from poly(ethylene glycol) diacrylates (PEGDA) or poly(ethylene glycol) dimethacrylates (PEGDMA) containing different ethylene glycol chain lengths by one-step UV-initiated polymerization. Methanol/ethyl ether and cyclohexanol/decanol were used as bi-porogen mixtures for the PEGDA and PEGDMA monoliths, respectively. Effects of PEG chain length, bi porogen ratio and reaction temperature on monolith morphology and back pressure were investigated. For tri- and tetra-ethylene glycol diacrylates (i.e., PEGDA 258 and PEGDA 302), most combinations of methanol and ethyl ether were effective in forming monoliths, while for diacrylates containing longer chain lengths (i.e., PEGDA 575 and PEGDA 700), polymerization became more sensitive to the bi porogen ratio. A similar tendency was also observed for PEGDMA monomers. Polymerization of monoliths was conducted at approximately 0 degrees C and room temperature, which produced significant differences in monolith morphology and permeability. Monoliths prepared from PEGDA 258 were found to provide the best chromatographic performance with respect to peak capacity and resolution in hydrophobic interaction chromatography (HIC). Detailed study of these monoliths demonstrated that chromatographic performance was not affected by changing the ratios of the two porogens, but resulted in almost identical retention times and comparable peak capacities. An optimized PEGDA 258 monolithic column was able to separate proteins using a 20-min elution gradient with a peak capacity of 62. Mass recoveries for test proteins were found to be greater than 90, indicating its excellent biocompatibility. All monoliths demonstrated nearly no swelling or shrinking in different polarity solvents, and most of them could be stored dry, indicating excellent stability due to their highly crosslinked networks. The preparation of these in situ polymerized single-monomer monolithic columns was highly reproducible. The relative standard deviation (RSD) values based on retention times of retained proteins were all within 2.2%, and in most cases, less than 1.2%. The RSD values based on peak areas were within 9.5%, and in most cases, less than 7.0%. The single-monomer synthesis approach clearly improves column-to-column reproducibility. PMID- 20576270 TI - A new anionic exchange stir bar sorptive extraction coating based on monolithic material for the extraction of inorganic anion. AB - A novel anionic exchange stir bar sorptive extraction (SBSE) coating based on poly(2-(methacryloyloxy)ethyltrimethylammonium chloride-co-divinylbenzene) monolithic material for the extraction of inorganic anion was prepared. The effect of preparation conditions such as ratio of functional monomer to cross linker, content of porogenic solvent on the extraction efficiencies were investigated in detailed. The monolithic material was characterized by elemental analysis, scanning electron microscopy and infrared spectroscopy. In order to investigate the extraction capacity of the new coating for inorganic anion, the new SBSE was combined with ionic chromatography with conductivity detection, Br-, NO3-, PO4(3-) and SO4(2-) were selected as detected solutes. Several extractive parameters, including pH value and ionic strength in sample matrix, desorption solvent, extraction and desorption time were optimized. The results showed that strongly ionic strength did not favor the extraction of anlaytes. Under the optimum experimental conditions, low detection limits (S/N=3) and quantification limits (S/N=10) of the proposed method for the target anions were achieved within the range of 0.92-2.62 and 3.03-9.25 microg/L, respectively. The method also showed good linearity, simplicity, practicality and low cost for the extraction inorganic anions. Finally, the proposed method was successfully used to detect the two different trademarks of commercial purified water with satisfactory recovery in the range of 70.0-92.6%. To the best of our knowledge, this is the first to use SBSE to enrich inorganic anions. PMID- 20576271 TI - A comparative study on different ionic liquids used as surfactants: Effect on thermal and mechanical properties of high-density polyethylene nanocomposites. AB - Dialkyl imidazolium and alkyl phosphonium salts were synthesized to be used as new surfactants for cationic exchange of layered silicates, such as montmorillonite (MMT). The synthesized phosphonium (P-MMT) or imidazolium ion (I MMT)-modified montmorillonites display a dramatically improved thermal degradation with respect to commonly used quaternary ammonium salts. This thermal degradation window can still be shifted toward higher temperatures after washing of modified clays. Two kinds of organic species can be identified onto clay: physically adsorbed species versus chemically adsorbed species. To evidence the impact of these thermally resistant ionic liquids, the modified montmorillonites were introduced in a great commodity polymer, i.e., high-density polyethylene. Thermoplastic nanocomposites with a very low amount of nanofillers were processed in melt by twin screw extrusion. If the thermal stability of polyethylene is slightly increased with only 2wt.% of thermostable made clays, the stiffness toughness compromise is well improved since a strong increase in modulus is achieved with both thermostable clays without loss of fracture properties. But these mechanical performances are mainly obtained with unwashed thermostable clays because the physically adsorbed organic species onto clay surfaces behave like a compatibilizer that helps both the dispersion into the PE matrix and improves the clay/matrix interface quality. PMID- 20576272 TI - Equilibrium and kinetic adsorption study of the adsorptive removal of Cr(VI) using modified wheat residue. AB - A new adsorbent modified from wheat residue was synthesized after reaction with epichlorohydrin and triethylamine by using the modifying agents of diethylenetriamine in the presence of organic medium of N,N-dimethylformamide. The performance of the modified wheat straw (MWS) was characterized by Fourier transform infrared spectroscopy and point of zero charge analysis. The adsorption was investigated in a batch adsorption system, including both equilibrium adsorption isotherms and kinetics. Results showed that MWR had great anion adsorbing capacity, due to the existence of a large number of introduced amino groups, and the value of pH(PZC) was around 5.0. Equilibrium data were analyzed using the Langmuir, Freundlich, and Temkin isotherm models and were found to be best represented by the Freundlich isotherm model. Evaluation of the adsorption process identified its endothermic nature. The maximum adsorption capacity of MWS for the removal of Cr(VI) was 322.58mg/g at 328K, indicating that MWS has high chromium removal efficiency, compared to other adsorbents reported. The kinetics of adsorption followed the pseudo-second-order kinetic equation. The mechanism of adsorption was investigated using the intraparticle diffusion model. Thermodynamic parameters (free energy change, enthalpy change, and entropy change) revealed that the adsorption of Cr(VI) onto MWS was endothermic and spontaneous; additionally, the adsorption can be characterized as an ion-exchange process. The results suggest that MWS is an inexpensive and efficient adsorbent for removing Cr(VI) ions from aqueous solution. PMID- 20576273 TI - Self-assembly of a series of random copolymers bearing amphiphilic side chains. AB - A novel series of comb-like random copolymers were prepared by polymerization of amphiphilic macromonomers, 2-(acrylamido)-octane sulfonic acid (AMC(8)S), 2 (acrylamido)-dodecane sulfonic acid (AMC(12)S), and 2-(acrylamido)-hexadecane sulfonic acid (AMC(16)S), with 2-(acrylamido)-2-methylpropanesulfonic acid (AMPS) respectively. The synthesis of the polymers with the same contents of amphiphilic units as side chains, but different chain length, enabled us to study the chain length dependence of their association in salt solution. Steady-state fluorescence measurements with pyrene as a polarity probe, quasielastic light scattering techniques (QELS) and transmission electron micrograph (TEM) were employed to investigate the associative properties of the system. The above investigations showed that all kinds of side chains begin to assemble at certain polymer concentrations and the critical aggregation concentration (CAC) decrease dramatically with the increase in the length and content of alkyl. An interesting phenomenon is that the assembly tends more favorably to occur among different molecules rather than within single molecule when the number of carbon atoms in the alkyl groups or the polymer concentration increases, leading to the formation of larger multimolecular micelle-like aggregate. The aim of the present work is to establish the fundamental preconditions of intramolecular and intermolecular association fashions for the polymers, which is useful for the exploitation of functional groups and contributes to the development of amphiphilic random polymers. PMID- 20576274 TI - The system of carbon tetrachloride and closed carbon nanotubes analyzed by a combination of molecular simulations, analytical modeling, and adsorption calorimetry. AB - Using the combined techniques of molecular simulation, simple analytical modeling, and adsorption calorimetry, we propose new models describing adsorption onto closed carbon nanotubes. The models are capable of describing the adsorption isotherms and calorimetric enthalpy of carbon tetrachloride adsorption measured on three different closed carbon nanotubes. It is shown that the assumption of the presence of two types of surface centers (high- and low-energy centers) on external tube surfaces is sufficient to describe experimental adsorption and calorimetric enthalpy data. PMID- 20576275 TI - The development of memory maintenance: children's use of phonological rehearsal and attentional refreshment in working memory tasks. AB - Past research suggests that children begin to phonologically rehearse at around 7 years of age. Less is known regarding the development of refreshment, an attention-based maintenance mechanism. Therefore, the use of these two maintenance methods by 6- and 8-year-olds was assessed using memory span tasks that varied in their opportunities for maintenance activity. Experiment 1 showed that nonverbal processing impaired both groups' performance to similar extents. Experiment 2 employed phonologically similar or dissimilar memory items and compared the effects of verbal versus nonverbal processing on recall. Both groups showed evidence of phonological maintenance under nonverbal processing but not under verbal processing. Furthermore, nonverbal processing again impaired recall. Verbal processing was also more detrimental to performance in 8-year-olds than in 6-year-olds. Together, the results suggest that nonverbal processing impairs recall by obstructing refreshment and that developmental change in maintenance between 6 and 8 years of age consists primarily of an increase in phonological rehearsal. PMID- 20576276 TI - The relationship between the perception of axes of symmetry and spatial memory during early childhood. AB - Early in development, there is a transition in spatial working memory (SWM). When remembering a location in a homogeneous space (e.g., in a sandbox), young children are biased toward the midline symmetry axis of the space. Over development, a transition occurs that leads to older children being biased away from midline. The dynamic field theory (DFT) explains this transition in biases as being caused by a change in the precision of neural interaction in SWM and improvements in the perception of midline. According to the DFT, young children perceive midline, but there is a quantitative improvement in the perception of midline over development. In the experiment reported here, children and adults needed to determine on which half of a large monitor a target was located. In support of the DFT, even the youngest children performed above chance at most locations, but performance also improved gradually with age. PMID- 20576277 TI - Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease. AB - The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer's disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p=0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p=0.04), and positively correlated with scores on memory tests (r=0.298, p=0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation. PMID- 20576278 TI - [Snoring analysis methods]. AB - Snore is a breathing sound that is originated during sleep, either nocturnal or diurnal. Snoring may be inspiratory, expiratory or it may occupy the whole breathing cycle. It is caused by the vibrations of the different tissues of the upper airway. Many procedures have been used to analyze it, from simple interrogation, to standardized questionnaires, to more sophisticated acoustic methods developed thanks to the advance of biomedical techniques in the last years. The present work describes the current state of the art of snoring analysis procedures. PMID- 20576279 TI - [Mitochondrial DNA depletion and POLG mutations in a patient with sensory ataxia, dysarthria and ophthalmoplegia]. AB - BACKGROUND AND OBJECTIVE: A broad spectrum of clinical disorders is produced by mutations in the DNA polymerase gamma mitochondrial (POLG) gene which are associated with altered mitochondrial DNA (mtDNA) integrity. The majority of disorders characterized by multiple mtDNA deletions present with progressive external ophthalmoplegia, though this feature is not usually found in syndromes caused by mtDNA depletion. We report on a patient having the clinical triad of sensory ataxic neuropathy, dysarthria and ophthalmoplegia (SANDO), POLG mutations and reduced muscle mtDNA content. PATIENT AND METHODS: The patient presented with sensory ataxic neuropathy, dysarthria and ophthalmoplegia. Diagnosis was established by using histological and genetic procedures (nerve biopsy, mtDNA molecular analysis in skeletal muscle and mutation screening in the POLG gene). RESULTS: Sural nerve biopsy showed marked loss of large myelinated fibers. Skeletal muscle analysis revealed multiple mtDNA deletions, a marked decrease in mtDNA copy number and pathogenic mutations in the POLG gene. CONCLUSIONS: POLG mutations must be considered in all patients with the cardinal findings of the SANDO phenotype, without taking into account the type of abnormalities encountered in the mitochondrial genome. PMID- 20576280 TI - Enzymatic preparation of 20(S, R)-protopanaxadiol by transformation of 20(S, R) Rg3 from black ginseng. AB - 20(S)-protopanaxadiol (PPD(S)) and 20(R)-protopanaxadiol (PPD(R)), the main metabolites of ginsenosides Rg3(S) and Rg3(R) in black ginseng, are potential candidates for anti-cancer therapy due to their pharmacological activities such as anti-tumor properties. In the present study, we report the preparation of PPD(S, R) by a combination of steaming and biotransformation treatments from ginseng. Aspergillus niger was isolated from soil and showed a strong ability to transform Rg3(S, R) into PPD(S, R) with 100% conversion. Furthermore, the enzymatic reactions were analyzed by reversed-phase HPLC, showing the biotransformation pathways: Rg3(S)-->Rh2(S)-->PPD(S) and Rg3(R)-->Rh2(R)- >PPD(R), respectively. In addition, 12 ginsenosides including 3 pairs of epimers, namely Rg3(S), Rg3(R), Rh2(S), Rh2(R), PPD(S) and PPD(R), were simultaneously determined by reversed-phase HPLC. Our study may be highly applicable for the preparation of PPD(S) and PPD(R) for medicinal purposes and also for commercial use. PMID- 20576281 TI - Phylogenetic analysis of a new Cetacean morbillivirus from a short-finned pilot whale stranded in the Canary Islands. AB - Cetacean morbillivirus (CeMV) is considered the most pathogenic virus in cetaceans. Three strains have been already described: the dolphin morbillivirus (DMV), the porpoise morbillivirus (PMV) and the tentatively named pilot whale morbillivirus (PWMV). This study describes the molecular characterization of a strain of CeMV detected in the brain of a short-finned pilot whale that had stranded in the Eastern Atlantic Ocean around the Canary Islands and that showed lesions compatible with morbilliviral disease. Sequences for the nucleoprotein, phosphoprotein, fusion protein and haemagglutinin genes were obtained. The phylogenetic study showed high homology (97%) with the PWMV strain previously detected from a long-finned pilot whale stranded in the Western Atlantic Ocean. These results support the existing classification of CeMV into three principal genetic clusters. PMID- 20576282 TI - Adrenal incidentaloma: does an adequate workup rule out surprises? AB - BACKGROUND: Adrenal incidentaloma remains a diagnostic challenge. Despite well established management guidelines, the long-term results of following these guidelines are unknown. We sought to determine how accurately these guidelines identify functioning incidentalomas and how often these guidelines result in adrenalectomy for benign tumors. METHODS: We catalogued adrenal incidentalomas from a retrospective review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation performed, and postoperative histologic diagnosis. RESULTS: Eighty-one of the 500 adrenalectomies performed were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for 42% of all tumors resected. CONCLUSION: Current guidelines accurately predict the functional status of adrenal incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas resected are benign tumors. PMID- 20576283 TI - Micro-RNA-181a regulates osteopontin-dependent metastatic function in hepatocellular cancer cell lines. AB - BACKGROUND: Osteopontin (OPN) is a variably expressed, secreted glycophosphoprotein that mediates the growth and metastases of hepatocellular cancer (HCC). MicroRNAs (miRNAs) may be responsible for variant OPN expression, interrupting translation by binding OPN messenger RNA (mRNA) in 3'-untranslated regions (UTRs). METHODS: A microarray analysis identified miRNAs of interest. Plasmid constructs using a luciferase reporter with variable OPN 3'UTR mutations were transfected into 2 HCC cell lines to determine miRNA regulation of OPN expression. Western blot analyses confirmed variable OPN expression in both cell lines. Invasion, adhesion, and migration evaluated metastatic behavior in Hep G2 and Hep 3B with modified miRNA and OPN expression. RESULTS: Hep 3B produces 36 x miRNA 181a compared with Hep G2. Luciferase activity after transfection with miRNA 181a precursor was decreased in both cell lines (P < .01); luciferase activity increased with miRNA 181a inhibitor transfection in both cell lines (P < .01). Hep 3B transfected with mutated OPN 3'UTR increased luciferase activity 108% (P < .01). Hep G2 transfected with miRNA precursor decreased OPN expression 5 x (P < .01) in Western blot analyses. Hep 3B transfection with miRNA precursor increased OPN expression 3 x (P < .01) in Western blot analyses. In vitro metastatic correlates increased in Hep 3B lines after transfection with siOPN and/or miRNA 181a inhibitor (P < .01). CONCLUSION: MiRNA 181a decreases OPN expression in HCC cell lines. This previously undescribed mechanism may confer metastatic characteristics to HCC. PMID- 20576284 TI - Characterization of elemental and structural composition of corrosion scales and deposits formed in drinking water distribution systems. AB - Corrosion scales and deposits formed within drinking water distribution systems (DWDSs) have the potential to retain inorganic contaminants. The objective of this study was to characterize the elemental and structural composition of extracted pipe solids and hydraulically-mobile deposits originating from representative DWDSs. Goethite (alpha-FeOOH), magnetite (Fe(3)O(4)) and siderite (FeCO(3)) were the primary crystalline phases identified in most of the selected samples. Among the major constituent elements of the deposits, iron was most prevalent followed, in the order of decreasing prevalence, by sulfur, organic carbon, calcium, inorganic carbon, phosphorus, manganese, magnesium, aluminum and zinc. The cumulative occurrence profiles of iron, sulfur, calcium and phosphorus for pipe specimens and flushed solids were similar. Comparison of relative occurrences of these elements indicates that hydraulic disturbances may have relatively less impact on the release of manganese, aluminum and zinc, but more impact on the release of organic carbon, inorganic carbon, and magnesium. PMID- 20576285 TI - Temporal variations in arsenic uptake by rice plants in Bangladesh: the role of iron plaque in paddy fields irrigated with groundwater. AB - The transfer of arsenic to rice grains is a human health issue of growing relevance in regions of southern Asia where shallow groundwater used for irrigation of paddy fields is elevated in As. In the present study, As and Fe concentrations in soil water and in the roots of rice plants, primarily the Fe plaque surrounding the roots, were monitored during the 4-month growing season at two sites irrigated with groundwater containing approximately 130microgl(-1) As and two control sites irrigated with water containing <15microgl(-1) As. At both sites irrigated with contaminated water, As concentrations in soil water increased from <10microgl(-1) to >1000microgl(-1) during the first five weeks of the growth season and then gradually declined to <10microgl(-1) during the last five weeks. At the two control sites, concentrations of As in soil water never exceeded 40microgl(-1). At both contaminated sites, the As content of roots and Fe plaque rose to 1000-1500mgkg(-1) towards the middle of the growth season. It then declined to approximately 300mgkg(-1) towards the end, a level still well above As concentration of approximately 100mgkg(-1) in roots and plaque measured throughout the growing season at the two control sites. These time series, combined with simple mass balance considerations, demonstrate that the formation of Fe plaque on the roots of rice plants by micro-aeration significantly limits the uptake of As by rice plants grown in paddy fields. Large variations in the As and Fe content of plant stems at two of the sites irrigated with contaminated water and one of the control sites were also recorded. The origin of these variations, particularly during the last month of the growth season, needs to be better understood because they are likely to influence the uptake of As in rice grains. PMID- 20576286 TI - SGO future forward: Our greatest challenges are our greatest opportunities. PMID- 20576287 TI - Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer. AB - OBJECTIVES: There is a need for identification of new biomarkers improving our understanding, diagnosis, and follow-up of ovarian cancer. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta superfamily, and GDF-15 overexpression has been found in several cancer forms but has not been explored in ovarian cancer. The aim of the study was to explore preoperative plasma concentration and tissue expression of growth differentiation factor (GDF)-15 in ovarian tumors. METHODS: GDF-15 concentration was measured by immunoradiometric assay in plasma samples from patients with invasive ovarian cancer (n=125), borderline ovarian tumor (BOT, n=43), and benign ovarian tumor (n=144), from healthy women (n=40), as well as in effusion samples (n=44) from women with advanced ovarian cancer. Sections of ovarian carcinoma (n=20), BOT (n=9), and cystadenoma (n=7) were immunostained for GDF-15. RESULTS: Median plasma GDF-15 concentration was elevated in ovarian cancer as compared to healthy controls and women with benign ovarian tumors or BOT (p<0.001). GDF-15 plasma concentration correlated inversely with survival time and was an independent predictor of survival, after correction for FIGO stage and age (p=0.01). GDF-15 protein was cytoplasmatically expressed in serous tumor cells and detectable in high concentrations in effusion samples. CONCLUSION: GDF-15 emerges as a new potential biomarker in ovarian cancer. PMID- 20576288 TI - A nanocapsular combinatorial sequential drug delivery system for antiangiogenesis and anticancer activities. AB - We reported a precise engineered nanocapsule encapsulating a neovasculature disruption agent, combretastatin A4 (CA4) in a matrix that was made up of paclitaxel (PTX) conjugated amphiphilic polyester. The nanocapsule was able to release CA4 and PTX sequentially for temporal antiangiogenesis and anticancer activities. The nanocapsule has a small particle size at 68 nm with narrow size distribution (approximately 0.15). Cellular uptake of the nanocapsule was efficient, and detectable at as early as 20 min, and drugs sequestered in the nanocapsule could exert effective therapeutic effects on tumor neovasculature and cancer cells, respectively. Biodistribution experiments demonstrated the long circulation of nanocapsule in body fluid and the preferential accumulation of nanocapsule in tumor. Both in vivo artificial pro-angiogenesis and tumor xenograft assays demonstrated the promising therapeutic effect of the nanocapsule on tumor vasculature disruption, tumor cell proliferation inhibition and tumor cell apoptosis induction. The intrasplenic liver metastasis experiment also confirmed the liver metastatic prevention capacity of this nanocapsule. In summary, the findings indicated that this dual drug loaded nanocapsule with sequential drug delivery capacity is a promising candidate in combinatorial therapy in fighting against cancer, and may open an avenue for cancer therapy and diagnosis. PMID- 20576290 TI - Reproductive toxic effects of sublethal cadmium on the marine polychaete Perinereis nuntia. AB - To gain insight into the reproductive toxicity of sublethal cadmium on marine polychaetes, Perinereis nuntia sandworms were exposed to cadmium via artificially contaminated seawater. Cadmium influence on sexual maturation, egg laying, fertilization, zygote hatching and vitellogenin expression levels were analyzed. Results indicated that 23.05 and 563.87 microg L(-1) cadmium significantly delayed sexual maturation. Fertilization rate was significantly inhibited by 563.87 microg L(-1) cadmium while lower concentrations showed no significant effect. Zygote hatching was significantly inhibited by cadmium concentrations greater than 1.12 microg L(-1). We identified a vitellogenin gene sequence in P. nuntia and found that mRNA transcription was significantly upregulated by cadmium. These results indicate that sublethal cadmium levels cause dose dependent reproductive toxicity on P. nuntia by inhibiting sexual maturation, fertilization and zygote hatching, and the increased expression of vitellogenin suggesting cadmium has strong feminization effects on polychaetes. PMID- 20576289 TI - The retention of extracellular matrix proteins and angiogenic and mitogenic cytokines in a decellularized porcine dermis. AB - Decellularized dermis materials demonstrate considerable utility in surgical procedures including hernia repair and breast reconstruction. A new decellularized porcine dermis material has been developed that retains many native extracellular matrix (ECM) proteins and cytokines. This material has substantial mechanical strength with maximum tensile strength of 141.7 +/- 85.4 (N/cm) and suture pull through strength of 47.0 +/- 14.0 (N). After processing, many ECM proteins remained in the material including collagen III, collagen IV, collagen VII, laminin and fibronectin. Glycosaminoglycans, including hyaluronic acid, were also preserved. Among several cytokines whose levels were quantified, more vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) were retained within this material than in comparable decellularized dermis materials. The retention of bioactivity was demonstrated in a cell culture assay. Because this decellularized porcine dermis material both retains significant strength and has substantial biological activity, it may promote rapid integration and repair in clinical applications. PMID- 20576291 TI - Leukemia-related mortality in towns lying in the vicinity of metal production and processing installations. AB - BACKGROUND: Releases to the environment of toxic substances stemming from industrial metal production and processing installations can pose a health problem to populations in their vicinity. OBJECTIVES: To investigate whether there might be excess leukemia-related mortality in populations residing in towns in the vicinity of Spanish metal industries included in the European Pollutant Emission Register. METHODS: Ecologic study designed to examine mortality due to leukemia at a municipal level, during the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using Poisson regression models, we analyzed: risk of dying from leukemia in a 5-kilometer zone around installations which had become operational prior to 1990; effect of pollution discharge route and type of industrial activity; and risk gradient within a 50-kilometer radius of such installations. RESULTS: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations (1.07, 1.02-1.13 in men; 1.05, 1.00-1.11 in women), with this being more elevated in the case of installations that released pollution to air versus water. On stratifying by type of industrial activity, statistically significant associations were also observed among women residing in the vicinity of galvanizing installations (1.58, 1.09 2.29) and surface-treatment installations using an electrolytic or chemical process (1.34, 1.10-1.62), which released pollution to air. There was an effect whereby risk increased with proximity to certain installations. CONCLUSIONS: The results suggest an association between risk of dying due to leukemia and proximity to Spanish metal industries. PMID- 20576292 TI - Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample. AB - BACKGROUND: We analyzed the association of previous course-of-illness and other variables of clinical interest with a high frequency of both depressive or (hypo)manic episodes controlling for the effect of socio-demographic characteristics. METHODS: A total of 108 outpatients with a DSM-IV diagnosis of bipolar disorder (BD) were recruited. A retrospective and naturalistic study was conducted to examine the number of affective episodes and their relationship with socio-demographic, clinical and course-of-illness variables, including adherence to medication, type of medication used and the use of addictive substances. The episode frequency was estimated as the number of "major instances" of depression, hypomania and mania during the illness. To classify the patients into two groups (higher and lower-episode frequency), we used the statistical criterion of median split. Results were analyzed with logistic regression models to control for the effects of potential confounders. RESULTS: A high episode frequency (nine or more episodes) was associated with age (36-55years), delay in diagnosis, poor adherence to medication and current use of antipsychotic medication. In addition, a high frequency of manic episodes (four or more) was associated with female sex, age (>36years) and a manic onset of the illness, whereas a high frequency of depressive episodes (five or more) was associated with delay in diagnosis and poor adherence to medication. LIMITATIONS: Cross-sectional study design. CONCLUSIONS: Avoiding delay in diagnosis and enhancing treatment adherence might be important targets for reducing recurrences in BD. PMID- 20576293 TI - Cholesterol and triglycerides in antipsychotic-naive patients with nonaffective psychosis. AB - Patients with psychosis have an increased prevalence of hyperlipidemia. We compared fasting concentrations of lipids in newly diagnosed, antipsychotic-naive patients with nonaffective psychosis (N=87) and control subjects (N=92). After accounting for gender, age, smoking, socioeconomic status, and body mass index, there was no significant difference between the two groups in total cholesterol, high-density lipoproteins, low-density lipoproteins, or triglycerides. PMID- 20576294 TI - A longitudinal study of child mental health and problem behaviours at 14 years of age following unplanned pregnancy. AB - A substantial minority of children are born as a consequence of an unplanned pregnancy. Yet little is known about the impact of unplanned/unwanted pregnancy (UP) on long-term health outcomes for children. This study aimed to examine the association between UP and child mental health and behavioural problems at 14 years, and whether this association is confounded or mediated by other variables. Data were from a pre-birth prospective study that included 4765 mothers and their children (48.4% female and 51.6% male) followed up from pregnancy to 14 years of the child's age in Brisbane, Australia. Child anxiety/depression, aggression, delinquency, attention problems, withdrawal problems, somatic complaints, social problems, thought problems, internalizing, externalizing and total problems were measured using the Achenbach's Youth Self Report at 14 years. Child smoking and alcohol consumption were self-reported at 14 years. UP was prospectively assessed at the first antenatal visit of pregnancy. UP as reported by mothers at first antenatal visit predicted elevated levels of problem behaviours and increased substance use in children at 14 years. The impact of UP on child mental health and problem behaviours is partly due to the confounding effect of other variables, such as maternal socio-demographic status, mental health and substance use during pregnancy. Further research is needed to investigate the mechanism of association between UP and child aggression and early alcohol consumption at 14 years. PMID- 20576295 TI - A selective high affinity ligand (SHAL) designed to bind to an over-expressed human antigen on non-Hodgkin's lymphoma also binds to canine B-cell lymphomas. AB - Therapies using antibodies directed against cell surface proteins have improved survival for human patients with non-Hodgkin's lymphoma (NHL). It is possible that similar immuno-therapeutic approaches may also benefit canine NHL patients. Unfortunately, variability between human and canine epitopes often limits the usefulness of such therapies in pet dogs. The Lym-1 antibody recognizes a unique epitope on HLA-DR10 that is expressed on the majority of human B-cell malignancies. The Lym-1 antibody has now been observed to bind to dog lymphocytes and B-cell NHL. Sequence comparisons and computer modeling of a human and three canine DRB1 proteins identified several orthologs of human HLA-DR10 expressed by dog lymphocytes. Immuno-staining confirmed the presence of proteins containing the Lym-1 epitope on dog lymphocytes and B-cell NHL. In addition, a selective high affinity ligand (SHAL) SH-7139 designed to bind within the Lym-1 epitope of HLA-DR10 was also observed to bind to canine B-cell NHL tissue. This SHAL, which is selectively cytotoxic to cells expressing HLA-DR10 and has been shown to cure mice bearing human B-cell lymphoma xenografts, may prove useful in treating B cell malignancies in pet dogs. PMID- 20576297 TI - Bimodal effect of interferon-beta on astrocyte proliferation and survival: Importance of nuclear factor-kappaB. AB - Accumulating evidence indicates that interferon-beta (IFN-beta) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-beta in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN beta treatment can either promote astrocyte proliferation and survival, or result astrocyte death. These actions depend, at least in part, on the regulation of nuclear factor-kappa B (NF-kappaB), an inducible transcription factor present in neurons and glia. This bimodal effect of IFN-beta adds a new layer of complexity in the actions of IFN-beta within the CNS. PMID- 20576296 TI - Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase-I in children with autism. AB - Autistic children show elevated serum levels of autoantibodies to several proteins essential for the function of normal brains. The voltage-dependent anion channel (VDAC) and hexokinase-I, a VDAC protective ligand, were identified as targets of this autoimmunity in autistic children. These autoantibodies were purified using immunoaffinity chromatographic techniques. Both antibodies induce apoptosis of cultured human neuroblastoma cells. Because VDAC and hexokinase-I are essential for brain protection from ischemic damage, the presence of these autoantibodies suggests a possible causal role in the neurologic pathogenesis of autism. PMID- 20576298 TI - A preliminary investigation of four-dimensional ultrasound for evaluation of middle ear ossicles: an in vitro study. AB - OBJECTIVE: Temporal bone imaging in children has several inherent limitations. Computed tomography has the disadvantage of ionizing radiation, possible sedation, cost and accessibility. Magnetic resonance imaging has most of these disadvantages, with the exception of radiation, and provides bone images of limited resolution. Recent advances in ultrasound have led to its increased application in numerous medical fields. The purpose of this study was to investigate the ability of four-dimensional ultrasound (4DUS) to image middle ear ossicles in vitro and determine if this technology should be adapted for future clinical use. METHODS: Thirty cadaveric ossicles (10 malleus, 10 incus, and 10 stapes) were randomized and measured by two evaluators under a microscope. The ossicles were then immersed in a cold water bath and imaged, randomized, and measured using four-dimensional ultrasound by the same two evaluators. A separate cadaveric temporal bone, modified to allow the ultrasound probe to rest on the tympanic membrane, was imaged to visualize the ossicles in situ and evaluate whether or not the tympanic membrane and malleus would impede visualization of more medial structures. RESULTS: Microscopic measurements were: malleus (h=8.0 mm+/-0.32, w=2.7 mm+/-0.20), incus (h=6.8 mm+/-0.41, w=5.3 mm+/-0.46), stapes (h=3.5 mm+/-0.34, w=2.4 mm+/-0.17). Inter-rater reliability was 0.8. Measurements were in agreement with previously published values. Ultrasound measurements were: malleus (h=8.0 mm+/-0.51, w=2.9 mm+/-0.27), incus (h=6.8 mm+/-0.49, w=5.5 mm+/ 0.42), stapes (h=3.6 mm+/-0.41, w=2.5 mm+/-0.19). Inter-rater reliability was 0.7. Mean intra-class correlation coefficient for microscopic and ultrasound measurements was 0.7. Images of the ossicular chain in continuity in the temporal bone specimen were not as clear as images of individual ossicles that were disarticulated and imaged under water. CONCLUSIONS: 4DUS provides reasonable images of ossicles disarticulated and mounted in underwater medium. However, images of the intact ossicular chain in a modified cadaveric temporal bone were not as clear, making interpretation difficult. Further investigation into the development of a thinner ultrasound probe that can pass through the external auditory canal and into overcoming limitations of air in the middle ear cleft are warranted. This could allow for a clinically relevant, faster, lower cost and lower risk alternative to current imaging techniques. PMID- 20576299 TI - Perturbation of object location during bimanual prehension: the role of visual feedback. AB - In this series of studies on the coordination of the two hands during a bimanual perturbation task, 10 right-handed volunteers were asked to reach to grasp and lift two illuminated cubic objects. Upon initiation of the reach a perturbation could occur by extinguishing one or both objects and illuminating new objects located directly away from the start position in the para-sagittal plane (Experiment 1) or toward the start position in the para-sagittal plane (Experiment 2). In Experiment 2 we also manipulated position of the targets within the visual span by having the targets move toward the midline or away from the midline. Dependent measures included kinematic data for the reach movement as well as the timing of eye movements. Results of both experiments indicated little interference between the hands when one object was perturbed while the other remained stationary. We hypothesize that when visual feedback about limb movement is available, participants can independently reorganize the trajectory of the perturbed limb with minimal interference on the non-perturbed limb. Furthermore, results of Experiment 2 indicated that the position of the targets within the visual span at the final target location dictates the number of eye movements made to acquire both targets and can lead to asynchronies at movement termination in a task-dependent manner. Finally, we found that when targets were perturbed away from the body movement time results indicated a right-hand advantage for dealing with a single perturbation. In contrast, perturbations toward the body abolished the movement time advantage. We suggest that differences in the use of visual feedback when working in the upper versus lower visual fields may influence hand advantages. PMID- 20576300 TI - Bacterial communities associated with the production of artisanal Istrian cheese. AB - In this work we report on the main bacterial microflora typical for fermentation and ripening of traditional Istrian cheese. Samples from milk as well as Istrian cheese were analyzed during the ripening process by using culture independent molecular fingerprinting methods as well as culture based approaches. Our results indicate changes in bacterial diversity pattern during the ripening process. Differences in bacterial diversity at the same ripening stage among different farms investigated were comparably low. Sequence analysis of the most prominent bands of denaturing gradient gel electrophoresis fingerprints revealed dominance of Lactococcus lactis subs. lactis in all samples and a strong presence of Enterococcus spp. which was also confirmed by plate count analysis. PMID- 20576301 TI - Effect of live Lactobacillus plantarum L2 on TNF-alpha-induced MCP-1 production in Caco-2 cells. AB - Lactobacillus plantarum is a commensal bacterium that is known to ameliorate intestinal injury and inflammation caused by a wide variety of enteric pathogens. We hypothesized that L. plantarum may exert its probiotic effects by attenuation of pro-inflammatory signaling induced by TNF-alpha. Caco-2 cells were stimulated with TNF-alpha in the presence of L. plantarum L2 and Lactobacillus acidophilus LA. The protein and mRNA levels of the pro-inflammatory cytokine, MCP-1, were measured by ELISA and RT-PCR, respectively. The effect of Lactobacillus bacteria on IkappaBalpha degradation was further studied by western blotting. L. plantarum L2 and L. acidophilus LA had no effect on mRNA expression and production of MCP-1 in Caco-2 cells. A significant elevation in MCP-1 mRNA and protein expression in Caco-2 cells was detected after a 4h exposure to TNF-alpha. Pre-incubation of Caco-2 cells with L. plantarum L2 for 2h resulted in an attenuation of both MCP-1 protein production and mRNA expression in TNF-alpha-stimulated cells. L. plantarum L2 also prevented IkappaBalpha degradation in TNF-alpha-stimulated Caco 2 cells. L. plantarum L2 inhibited MCP-1 secretion and mRNA expression via a NF kappaB dependent pathway by interfering with IkappaBalpha degradation in TNF alpha-stimulated Caco-2 cells. PMID- 20576302 TI - Resistance of Cronobacter sakazakii in reconstituted powdered infant formula during ultrasound at controlled temperatures: a quantitative approach on microbial responses. AB - Many of the documented outbreaks of Cronobacter sakazakii have been linked to infant formula. The aims of this work are to monitor the inactivation kinetics of C.sakazakii NCTC 08155 and ATCC 11467 and to determine quantitatively the effectiveness of ultrasonic treatments as an alternative to heat processing of reconstituted infant milk formula before feeding of infants at highest risk. Inactivation studies of C. sakazakii inoculated in reconstituted infant formula were performed at the combined conditions of temperature, i.e., 25 degrees C, 35 degrees C, 50 degrees C and amplitude, i.e., 24.4, 30.5, 42.7, 54.9, 61 microm and the kinetics were described by a range of inactivation models. The dependency of the specific inactivation rate with respect to the product of temperature and amplitude was described by a modified Bigelow type model. Ultrasound combined with temperature was efficient to reduce significantly the microbial levels of C. sakazakii. C. sakazakii strain NCTC 08155 was at the same range of temperature and amplitude resistance as strain ATCC 11467. Application of ultrasound is an alternative process for the production of safe reconstituted infant formula. This study contributes on the quantitative assessment of the resistance of C. sakazakii. PMID- 20576303 TI - Ethanol, vinegar and Origanum vulgare oil vapour suppress the development of anthracnose rot in tomato fruit. AB - Anthracnose rot (Colletotrichum coccodes) development in vitro or in tomato (Lycopersicon esculentum L.) fruit was evaluated after treatment with absolute ethyl alcohol (AEA), vinegar (VIN), chlorine (CHL) or origanum oil (ORI) and storage at 12 degrees C and 95% relative humidity during or following exposure to the volatiles. Fruit treated with vapours reduced fungal spore germination/production, but in the case of AEA- and VIN-treated fruits, fungal mycelium development was accelerated. Fruit lesion development was suppressed after fruit exposure to pure (100% v/v) AEA or ORI vapours which were accompanied by increased fruit cracking. Exposure to pure VIN-, CHL- and ORI vapours reduced (up to 92%) spore germination in vitro, but no differences were observed in the AEA treatment. The benefits associated with volatiles-enrichment were maintained in fruit pre-exposed to vapours, resulting in suppression in spore germination and spore production. However, studies performed on fungi grown on Potato Dextrose Agar revealed fewer direct effects of volatiles on fungal colony development and spore germination per se, implying that suppression of pathogen development was due in a large part to the impact of volatiles on fruit-pathogen interactions and/or 'memory' effects on fruit tissue. Work is currently focussing on the mechanisms underlying the impacts of volatiles on fruit quality related attributes. The results of this study indicate that volatiles may be considered as an alternative to the traditional postharvest sanitizing techniques. Each commodity needs to be individually assessed, and the volatile concentration and sanitising technique optimised, before the volatile treatment is used commercially. PMID- 20576304 TI - Hierarchical Bayesian Modelling for Saccharomyces cerevisiae population dynamics. AB - Hierarchical Bayesian Modelling is powerful however under-used to model and evaluate the risks associated with the development of pathogens in food industry, to predict exotic invasions, species extinctions and development of emerging diseases, or to assess chemical risks. Modelling population dynamics of Saccharomyces cerevisiae considering its biodiversity and other sources of variability is crucial for selecting strains meeting industrial needs. Using this approach, we studied the population dynamics of S. cerevisiae, the domesticated yeast, widely encountered in food industry, notably in brewery, vinery, bakery and distillery. We relied on a logistic equation to estimate the key variables of population growth, but we took also into account factors able to affect them, namely environmental effects, genetic diversity and measurement errors. Our probabilistic approach allowed us: (i) to model the dynamical behaviour of strains in a given condition under some uncertainty, (ii) to measure environmental effects and (iii) to evaluate genetic variability of the growth key variables. PMID- 20576305 TI - Caesarean section and macrosomia increase transient tachypnoea of the newborn in type 1 diabetes pregnancies. AB - We determined whether transient tachypnoea of the newborn (TTN) is more common in macrosomic versus normal weight infants and in those delivered by caesarean section versus vaginally, in a retrospective cohort analysis of 212 type 1 diabetes pregnancies. Caesarean section and macrosomia were both associated with higher TTN rates. PMID- 20576306 TI - Breaking self-tolerance toward cytochrome P4502E1 (CYP2E1) in chronic hepatitis C: possible role for molecular mimicry. AB - BACKGROUND & AIMS: Circulating auto-antibodies targeting conformational antigens on cytochrome P4502E1 (CYP2E1) are detectable in patients with chronic hepatitis C (CHC) and are associated with more severe necro-inflammation. This study investigated the antigen specificity and the possible origin of these auto antibodies. METHODS: CYP2E1 site-directed mutagenesis and molecular simulation were used to characterize the epitope specificity of CHC-associated anti-CYP2E1 auto-antibodies. RESULTS: Immunoprecipitation experiments using differently mutated human CYP2E1s revealed that conformational anti-CYP2E1 antibodies targeted two epitopes located on the molecule surface in an area between Lys(324) Glu(346) at J-K'' helices overlapping. Such epitopes were not recognized by the sera targeting linear CYP2E1 antigens. The CYP2E1(324-346) peptide showed good homology with two sequences (NS5b(438-449) and NS5b(456-465)) within the NS5b protein of hepatitis C virus (HCV). Consistently, conformational anti-CYP2E1 IgG bind to GST-conjugated NS5b(438-449) and NS5b(456-465) more efficiently than those recognizing CYP2E1 linear antigens. Competition experiments confirmed the cross-reactivity of conformational anti-CYP2E1 IgG with both NS5b(438-449) and NS5b(456-465). Moreover, mice immunized with GST-conjugated NS5b(438-449) or NS5b(456-465) peptides developed antibodies recognizing human CYP2E1. CONCLUSIONS: In CHC patients cross-reactivity between CYP2E1 and specific sequences in HCV-NS5b protein can promote the development of auto-antibodies targeting conformational epitopes on the CYP2E1 surface that might contribute to hepatic injury. PMID- 20576307 TI - Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients. AB - BACKGROUND & AIMS: A common genetic variation at the IL28 locus has been found to affect the response of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. An allele associated with a favorable response (rs8099917 T), which is the major allele in the majority of Asian, American, and European populations, has also been found to be associated with spontaneous eradication of the virus. METHODS: As no studies have yet analyzed the effect of the polymorphism on biochemical and inflammatory changes in chronic infection, we analyzed a cohort of patients with chronic hepatitis C (n=364) for the effect of the IL28 polymorphism on viral, biochemical, and histological findings. RESULTS: We found that the proportion of HCV wild type core amino acids 70 and 91 was significantly greater (p=1.21 x 10(-4) and 0.034) and levels of gamma-GTP significantly lower (p=0.001) in patients homozygous for the IL28 major allele. We also found that inflammation activity and fibrosis of the liver were significantly more severe in patients homozygous for the IL28 major allele (p=0.025 and 0.036, respectively). Although the higher gamma-GTP levels were also associated with higher inflammatory activity and fibrosis, multivariate analysis showed that only the IL28 allele polymorphism, sex, alcohol consumption, and liver fibrosis were independently associated with gamma-GTP levels (p=0.001, 0.0003, 0.0013, and 0.0348, respectively). CONCLUSIONS: These results suggest that different cytokine profiles induced by the IL28 polymorphism resulted in different biochemical and inflammatory conditions during chronic HCV infection and contribute to the progression of liver diseases. PMID- 20576308 TI - Inequity in a market-based health system: Evidence from Canada's dental sector. AB - We study the extent and drivers of income-related inequity in utilization of dental services in Canada using the concentration-index approach that has been widely applied to study inequity in physician and hospital services. Because dental care is almost wholly privately financed in Canada, our estimates provide a benchmark for income-related inequity of utilization in private health systems. Although a number of studies document a link between income and utilization, our study is one of the few measuring income-related inequity in dental care utilization. A unique feature of our study is that we analyze separately inequity in total dental visits and in preventive visits. This is important because the case for equity is much clearer for preventive dental care. We also examine the impact of controlling for need using a wider variety of need indicators than previous analyses. We confirm that most oral health indicators perform poorly as need adjustors because they reflect past dental care use: individuals with higher levels of utilization also are in better oral health. Our most important finding is that access to preventive care is the most "pro-rich" type of dental care utilization and that income-related inequity in preventive dental care utilization is three times larger than what is measured for specialist services utilization in Canada. PMID- 20576309 TI - Socio-economic inequalities in child survival in India: a decomposition analysis. AB - This paper provides a first time assessment of the decomposed contributions of socio-economic determinants of under2 child mortality in India and its states using the recent National Family Health Survey (NFHS-3, 2005-06) data. In the first stage analysis, concentration indices of under2 mortality were generated as measures of socio-economic inequalities. The concentration indices were then decomposed into their determining factors. Decomposition results reveal that poor household economic status (46%), mother's illiteracy (35%) and rural residence (15%) contribute to 96% of total socio-economic inequalities in child survival at the national level. The contribution of economic status is relatively smaller in 5 states that are advanced in health transition. The varying pattern of evidence across the states from decomposition analysis suggests the need for unique health intervention strategies for different states in accordance with the evidence of major contributions to total child health inequalities arising from poverty, illiteracy and rural residence. PMID- 20576310 TI - Graphical simulation environments for modelling and simulation of integrative physiology. AB - Guyton's original integrative physiology model was a milestone in integrative physiology, combining significant physiological knowledge with an engineering perspective to develop a computational diagrammatic model. It is still used in research and teaching, with a small number of variants on the model also in circulation. However, though new research has added significantly to the knowledge represented by Guyton's model, and significant advances have been made in computing and simulation software, an accepted common platform to integrate this new knowledge has not emerged. This paper discusses the issues in the selection of a suitable platform, together with a number of current possibilities, and suggests a graphical computing environment for modelling and simulation. By way of example, a validated version of Guyton's 1992 model, implemented in the ubiquitous Simulink environment, is presented which provides a hierarchical representation amenable to extension and suitable for teaching and research uses. It is designed to appeal to the biomedical engineer and physiologist alike. PMID- 20576311 TI - Systems engineering principles for the design of biomedical signal processing systems. AB - Systems engineering aims to produce reliable systems which function according to specification. In this paper we follow a systems engineering approach to design a biomedical signal processing system. We discuss requirements capturing, specification definition, implementation and testing of a classification system. These steps are executed as formal as possible. The requirements, which motivate the system design, are based on diabetes research. The main requirement for the classification system is to be a reliable component of a machine which controls diabetes. Reliability is very important, because uncontrolled diabetes may lead to hyperglycaemia (raised blood sugar) and over a period of time may cause serious damage to many of the body systems, especially the nerves and blood vessels. In a second step, these requirements are refined into a formal CSP|| B model. The formal model expresses the system functionality in a clear and semantically strong way. Subsequently, the proven system model was translated into an implementation. This implementation was tested with use cases and failure cases. Formal modeling and automated model checking gave us deep insight in the system functionality. This insight enabled us to create a reliable and trustworthy implementation. With extensive tests we established trust in the reliability of the implementation. PMID- 20576313 TI - Endothelial nitric oxide synthase limits the inflammatory response in mouse cutaneous leishmaniasis. AB - Endothelial nitric oxide synthase (eNOS) was originally discovered in the cardiovascular system, where it contributes to the regulation of blood pressure and the inhibition of platelet adhesion. Considering that the vascular endothelium is critical for the initiation of inflammatory processes and that eNOS has been detected in certain types of immune cells, we investigated the function of eNOS in C57BL/6 mice infected with Leishmania major, a protozoan parasite that causes a chronic, but self-healing skin disease. C57BL/6 eNOS(-/-) mice developed more severe (but ultimately resolving) skin lesions with strikingly higher numbers of parasites compared to wildtype controls. In accordance with our finding that naive T lymphocytes and Th1 cells (as well as Th2 cells) did not express eNOS after stimulation and that eNOS was not required for Th1 differentiation in vitro, lymph node T cells from L. major-infected wildtype and eNOS(-/-) mice released comparable amounts of IFN-gamma and proliferated equally well. Immunohistological analyses revealed that the expression of inducible NO synthase in the skin and draining lymph nodes of infected mice was completely preserved in the absence of eNOS. However, the skin lesions of eNOS(-/-) mice were characterized by massive infiltrates of granulocytes, which in vitro similar to inflammatory macrophages failed to express eNOS. From these data, we conclude that during cutaneous leishmaniasis eNOS-derived NO, presumably released by vascular endothelial cells, counteracts the recruitment of granulocytes, which are known to function as host cells and trojan horses for Leishmania parasites, and thereby limits the severity of the skin lesions. PMID- 20576312 TI - Therapy of small cell lung cancer with emphasis on oral topotecan. AB - Systemic chemotherapy plays the major role in the management of patients with small cell lung cancer. Cisplatin plus etoposide is the most widely used regimen and is considered as standard in patients with limited disease. Cisplatin plus irinotecan improved survival compared to cisplatin plus etoposide in a Japanese trial but failed to do so in two trials in Caucasians. Cisplatin plus topotecan had similar efficacy compared to cisplatin plus etoposide in patients with extensive disease. In the second-line setting, topotecan showed similar efficacy but better tolerability compared to cyclophosphamide, doxorubin plus vincristine. Oral topotecan was as efficacious as its intravenous formulation and was shown to improve survival compared to best supportive care alone in patients previously treated with chemotherapy. Thus topotecan is considered as the standard second line chemotherapy in patients with small cell lung cancer. PMID- 20576314 TI - Eukaryotic expression of functionally active recombinant soluble CD83 from HEK 293T cells. AB - The cell surface protein CD83 belongs to the immunoglobulin super family and is highly expressed on mature dendritic cells (DCs). A membrane bound and a soluble form of CD83 (sCD83) have been described. Previously, the isolation of a purified recombinant sCD83 molecule from bacterial cultures using high pressure liquid chromatography was reported. This recombinant protein reduced DC-mediated T cell proliferation in vitro and displayed an inhibitory effect in the experimental autoimmune encephalomyelitis (EAE) model. When purifying sCD83 from bacteria, however, a lipopolysaccharide fraction is frequently co-isolated with the recombinant sCD83 protein. Moreover, the subsequent separation of sCD83 from contaminating LPS is usually accompanied by a considerable loss of soluble CD83. A further disadvantage of soluble CD83 expression in prokaryotic cells is the lack of functional glycosylation. To overcome these problems, we developed an alternative strategy to express sCD83 in eukaryotic human embryonic kidney (HEK) 293 T cells. Using this system, we showed that recombinant sCD83 was LPS-free and effectively glycosylated with all three asparagine residues at least partially involved. The functionality of the expressed sCD83 protein was examined using the mixed lymphocyte reaction (MLR) assay, demonstrating a reduced DC-mediated T cell proliferation as previously reported for the sCD83 protein purified from E. coli. Thus, a new protocol for efficient eukaryotic expression and purification of sCD83 was established, which might have several advantages compared to prokaryotic expression systems. PMID- 20576315 TI - Potent cryoprotective activity of cold and CO2-regulated cherimoya (Annona cherimola) endochitinase. AB - A cryoprotective chitinase (BChi14) was isolated and purified from the mesocarp of CO(2)-treated cherimoya fruit (Annona cherimola Mill.) stored at chilling temperature by anion exchange and chromatofocusing chromatography. This hydrolase was characterized as an endochitinase with a M(r) of 14.31 kDa and a pI of 8.26, belonging to the family 19 of glycosyl hydrolases (GH19). While it was stable over a wide pH range and active in a broad acidic pH range, it had an optimum pH of 7.0. Its optimum temperature was low, 35 degrees C, and it retained about 30% of its maximum activity at 5 degrees C. Moreover, BChi14 was relatively heat unstable and its activity was progressively lost at temperatures above 50 degrees C. Kinetic studies revealed many similarities with other plant endochitinases. However, BChi14 had high k(cat) (6.93 s(-1)) value for the fluorogenic substrate 4-MU-(GlcNAc)(3), reflecting its great catalytic efficiency. Moreover, a thermodynamic characterization revealed that the purified enzyme displayed a high k(cat) at 37 and 5 degrees C, and a low E(a) (11.32 kJ mol(-1)). In vitro functional studies indicated that BChi14 had no effect on the inhibition of Botrytis cinerea hyphal growth and no antifreeze activity, as shown by the thermal hysteresis analysis using differential scanning calorimetry. However, the purified endochitinase showed very strong cryoprotective activity against freeze thaw inactivation of lactate dehydrogenase. The PD(50) was 12.5 times higher than that of the cryoprotective protein BSA, and 2 or 3 orders of magnitude greater than sucrose, comparable with that of most cryoactive plant dehydrins. These results, together with the consolidated microstructure and the integrity of CO(2) treated mesocarp tissue, indicate that BChi14 is functionally implicated in the mechanisms underlying chilling tolerance activated by high CO(2) concentrations. PMID- 20576316 TI - The ABRE-binding bZIP transcription factor OsABF2 is a positive regulator of abiotic stress and ABA signaling in rice. AB - Abscisic acid (ABA) is an important phytohormone involved in abiotic stress tolerance in plants. The group A bZIP transcription factors play important roles in the ABA signaling pathway in Arabidopsis but little is known about their functions in rice. In our current study, we have isolated and characterized a group A bZIP transcription factor in rice, OsABF2 (Oryza sativa ABA-responsive element binding factor 2). It was found to be expressed in various tissues in rice and induced by different types of abiotic stress treatments such as drought, salinity, cold, oxidative stress, and ABA. Subcellular localization analysis in maize protoplasts using a GFP fusion vector indicated that OsABF2 is a nuclear protein. In yeast experiments, OsABF2 was shown to bind to ABA-responsive elements (ABREs) and its N-terminal region found to be necessary to transactivate a downstream reporter gene. A homozygous T-DNA insertional mutant of OsABF2 is more sensitive to salinity, drought, and oxidative stress compared with wild type plants. In addition, this Osabf2 mutant showed a significantly decreased sensitivity to high levels of ABA at germination and post-germination. Collectively, our present results indicate that OsABF2 functions as a transcriptional regulator that modulates the expression of abiotic stress responsive genes through an ABA-dependent pathway. PMID- 20576317 TI - Characterization of photosystem II photochemistry in transgenic tobacco plants with lowered Rubisco activase content. AB - Rubisco activase plays an important role in the regulation of CO(2) assimilation. However, it is unknown how activase regulates photosystem II (PSII) photochemistry. To investigate the effects of Rubisco activase on PSII photochemistry, we obtained transgenic tobacco (Nicotiana tabacum) plants with 50% (i7), 25% (i28), and 5% (i46) activase levels as compared to wild type plants by using a gene encoding tobacco activase for the RNAi construct. Both CO(2) assimilation and PSII activity were significantly reduced only in transgenic i28 and i46 plants, suggesting that activase deficiency led to decreased PSII activity. Flash-induced fluorescence kinetics indicated that activase deficiency resulted in a slow electron transfer between Q(A) (primary quinine electron acceptor of PSII) and Q(B) (secondary quinone electron acceptor of PSII). Thermoluminescence measurements revealed that activase deficiency induced a shift of S(2)Q(A)(-) and S(2)Q(B)(-) recombinations to higher temperatures in parallel, and a decrease in the intensities of the thermoluminescence emissions. Activase deficiency also dampened the period-four oscillation of the thermoluminescence B band. Protein gel blot analysis showed that activase deficiency resulted in a significant decrease in the content of D1, D2, CP43, CP47, and PsbO proteins. Transmission electron microscopy analysis demonstrated that activase deficiency induced a significant decrease in the number of grana stacks per chloroplast and discs per grana stack. Our results suggest that activase plays an important role in maintaining PSII function and chloroplast development. PMID- 20576318 TI - Identification of three relationships linking cadmium accumulation to cadmium tolerance and zinc and citrate accumulation in lettuce. AB - Lettuce (Lactuca sativa) is a plant species that shows high accumulation of cadmium, a toxic heavy metal. Lettuce is therefore a good model both for identifying determinants controlling cadmium accumulation in plant tissues and for developing breeding strategies aimed at limiting cadmium accumulation in edible tissues. In this work, 14-day-old plants from three lettuce varieties were grown for 8 days on media supplemented with cadmium concentrations ranging from 0 to 50 microM. Growth, as well as Cd(2+), Zn(2+), K(+), Ca(2+), NO(3)(-), SO(4)(2 ), Cl(-), phosphate, malate and citrate root an shoot contents were analyzed. The three lettuce varieties Paris Island Cos, Red Salad Bowl and Kordaat displayed differential abilities to accumulate cadmium in roots and shoots, Paris Island Cos displaying the lowest cadmium content and Kordaat the highest. From the global analysis of the three varieties, three main trends were identified. First, a common negative correlation linked cadmium tissue content and relative dry weight reduction in response to cadmium treatments in the three varieties. Second, increasing cadmium concentration in the culture medium resulted in a parallel increase in zinc tissue content in all lettuce varieties. A common strong positive correlation between cadmium and zinc contents was observed for all varieties. This suggested that systems enabling zinc and cadmium transport were induced by cadmium. Finally, the cadmium treatments had a contrasting effect on anion contents in tissues. Interestingly, citrate content in shoots was correlated with cadmium translocation from roots to shoots, suggesting that citrate might play a role in cadmium transport in the xylem vessels. Altogether, these results shed light on three main strategies developed by lettuce to cope with cadmium, which could help to develop breeding strategies aimed at limiting cadmium accumulation in lettuce. PMID- 20576319 TI - Wound healing in the 21st century. AB - Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing. PMID- 20576320 TI - The canary seems fine: the effects of the economy on job-seeking experiences of recent dermatology training program graduates. PMID- 20576321 TI - Newspaper reporting of meticillin-resistant Staphylococcus aureus and 'the dirty hospital'. AB - A distinctive tone is apparent in UK press coverage of meticillin-resistant Staphylococcus aureus (MRSA), dominated by the metaphor of 'the dirty hospital', which emphasises defects in hospital cleanliness and failures of government and National Health Service management. We found no primary evidence for a linkage between hospital cleanliness and MRSA incidence in publicly available data. We therefore sought the sources of this type of reporting. A textual analysis of all articles (2000-2007) about MRSA in the UK national press was performed to detect a bias towards reporting MRSA in terms of hospital cleanliness over other accepted risk factors for MRSA. This was supplemented by interviews with eight journalists and a detailed chronology of newspaper and other media releases in February 2000, seeking reasons why hospital cleanliness and MRSA have been linked. There is a strong bias in newspaper coverage of MRSA to link this infection with hospital cleanliness. The events around reporting of a National Audit Office publication in February 2000 appear to be particularly important in defining the cause of MRSA as dirty hospitals. The metaphor of 'the dirty hospital' was derived from, and was a distortion of, official reports from government departments. It had a certain evocative power, with public acceptance, and so became used by journalists, on the one side, and by politicians, government officials and ministers on the other, in a cycle of mutual reinforcement. PMID- 20576322 TI - [40 years after the description of the Swan Ganz Catheter]. PMID- 20576323 TI - [Bioethics beyond the dilemmas]. PMID- 20576324 TI - [Sarcoidosis of bone. Findings in the Gallium citrate examination]. AB - Sarcoidosis of bone lesions are rare, with an overall incidence of 3-9% of the cases. When they do occur, they are more frequent in the small bones of hands and feet than in long bones, spine or skull. We report a case of a male patient with sarcoidosis with multiple enlarged lymph nodes, skin and bone lesions, and the scintigraphic findings. PMID- 20576325 TI - [Relationship between publications on non-gastrointestinal bacterial zoonoses and the incidence of the diseases in Spain]. PMID- 20576327 TI - Design, synthesis, and antitubercular evaluation of novel series of 3-benzofuran 5-aryl-1-pyrazolyl-pyridylmethanone and 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4 oxo-naphthyridin analogs. AB - Twenty-eight newer 3-benzofuran-5-aryl-1-pyrazolyl-pyridylmethanone and 3 benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin analogs were synthesized by microwave irradiation method and evaluated for in-vitro and in-vivo antitubercular activity against multidrug-resistant M. tuberculosis stains. Structure-activity relationship study was carried out and found NO(2) (o) substituted 3-benzofuran-5-aryl-1-pyrazolylcarbonyl-4-oxo-naphthyridin was most potent antitubercular agent against M. tuberculosis, even better than standard drug isoniazid and comparable with rifampin. Other synthesized compounds 7j, 7f, 7a, 7e and 5d, 5f were found moderate to good activity in in-vitro model at lower IC(50) values 85 microM, 154 microM, 157 microM, 164 microM, 170 microM and 190 microML respectively. In in-vivo animal model compound 7j was drastically reduced the bacterial load in lung and spleen tissues at the dose of 25 mg/kg body weight. PMID- 20576328 TI - Antimony(III) complexes with 2-benzoylpyridine-derived thiosemicarbazones: cytotoxicity against human leukemia cell lines. AB - The antimony(III) complexes [Sb(2Bz4DH)Cl(2)] (1), [Sb(H2Bz4M)Cl(3)] x 2 H(2)O (2) and [Sb(2Bz4Ph)Cl(2)] (3) were obtained with 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N(4)-methyl (H2Bz4M) and N(4)-phenyl (H2Bz4Ph) derivatives. H2Bz4DH, H2Bz4Ph and complexes (1-3) exhibited high cytotoxic activity against HL-60 and Jurkat human leukemia cell lines. When these compounds were tested against HL-60 cells with ectopic expression of BcrAbl, Bcl 2 or Bcl-X(L), which confer resistance to apoptosis against a variety of death inducing agents, the cytotoxicity was much lower, indicating apoptosis to be part of their mechanism of action. The cytotoxic activity of complexes 2 and 3 against HL-60 and Jurkat cells was significantly higher than that of the corresponding thiosemicarbazones, suggesting coordination to be an interesting strategy of cytotoxic dose reduction. PMID- 20576330 TI - [Birt-Hogg-Dube syndrome and multiple recurrent tumors]. AB - Birt-Hogg-Dube (SBHD) syndrome is a rare autosomal dominant genodermatosis, predisposing to the occurrence of tumors associated with skin manifestations. We report a male patient who presented with a history of recurrent pneumothorax and was treated by nephrectomy for a left kidney carcinoma at 20 years old. Skin examination disclosed numerous fibrofolliculomas of the scalp. During follow-up, surgical resection of parotid oncocytomas and of a parathyroid adenoma were performed. SBHD was confirmed by molecular biology. In the presence of fibrofolliculomas and kidney tumors and recurrent spontaneous pneumothorax, a diagnosis of SHBD syndrome should be discussed, and tests need to be performed on the whole family. PMID- 20576329 TI - 3-Formylchromones: potential antiinflammatory agents. AB - The synthesis and characterization of 3-formylchromone (1) and its derivatives 2 24 and evaluation of their potential antiinflammatory activities is reported here. These compounds were characterized by (1)H NMR, EI MS, IR, and UV spectroscopic techniques and elemental analysis. The synthesized compounds were evaluated by using various in vitro and in vivo assay models for antiinflammatory activity and their effects were compared with known standard drug such as aspirin and indomethacin. Among all tested compounds, 1, 2, 5, 6, 9, 14, 16-19, 21-23, showed promising antiinflammatory activities. The results and SAR has been discussed in this report. PMID- 20576331 TI - [TRAPS: clinical significance of genotype. A report of two cases]. AB - INTRODUCTION: Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) is defined as recurrent attacks of generalized inflammation for which no infectious or auto-immune cause can be identified; it is caused by dominantly inherited mutations in the gene encoding the first TNF receptor. We report two additional cases of patients with TRAPS, suggesting that mutation pattern of TNFRSF 1A gene may influence the TRAPS phenotype. CASE REPORTS: The first patient, with a C30S mutation, exhibited severe digestive clinical manifestations; because the patient required high-dose corticosteroids regimen to improve TRAPS manifestations, he was further given successfully etanercept. The second patient, with a R92Q mutation of TNFRSF 1A gene, presented with moderate symptoms; TRAPS outcome was favourable after corticosteroid therapy initiation. CONCLUSION: Therefore, R92Q may be associated with a mild disease phenotype. On the other hand, C30S mutation appears to be associated with a severe phenotype, leading to an increased risk of amyloidosis. These findings suggest that these latter patients may require a closer follow-up. PMID- 20576332 TI - Therapeutical use of probiotic formulations in clinical practice. AB - BACKGROUND & AIMS: The spreading of gastrointestinal diseases is growing all over the world. Although for some of them an effective therapeutic approach has been found, palliation rather than cure is very frequent due to a partial knowledge of their aetiology and pathogenesis. This review, analyzing the main clinical studies, aims at being a state of the art update of the use of probiotic formulations in daily practice. METHODS: In this review we include all the most significant clinical trials involving the use of probiotic formulations for the treatment of several pathologies. RESULTS: Dysbiosis has been observed in irritable bowel syndrome patients. Probiotics may exert a beneficial effect on Crohn's disease affected patients who have shown gut microbiota antigens and altered wall permeability. Moreover some probiotic formulations seem to enhance the therapy for Helicobacter Pylori reducing its pathogenic potential. Intestinal ecology imbalance has been also linked to cancer induction, allergy, skin and urogenital diseases. In addition probiotics administration seems to be particularly useful to ease post-operative complications. CONCLUSION: Further future clinical trials, involving large numbers of patients, will be mandatory to achieve definite evidence of the preventive and curative role of probiotics in medical practice. PMID- 20576333 TI - An unusual complication of a parotidectomy. PMID- 20576334 TI - Reclaiming direct-entry midwifery training in Brazil: context, challenges and perspectives. PMID- 20576335 TI - Modified flapless dental implant surgery for planning treatment in a maxilla including sinus lift augmentation through use of virtual surgical planning and a 3-dimensional model. AB - PURPOSE: The concept of "prosthetic-driven implantology" may be considered a turning point in the history of modern dental implantology. On the basis of this sophisticated approach, the available bone and the optimal prosthetic position of the future restoration are checked before surgical intervention. However, the major drawback of today's prosthodontic discipline is that it is inherently 2 dimensional in nature, which may prevent the appropriate treatment; this problem can be overcome by the 3-dimensional capability of a computer-assisted approach when performed judiciously. It was proposed that this technique has the potential to provide a high level of safety and accuracy in comparison to traditional surgical procedures. MATERIALS AND METHODS: Using a novel approach, we performed modified flapless implant surgery accompanied by a simultaneous sinus-lifting procedure. The technique used a 3-dimensional life-sized computer-aided design/computer-aided manufacturing (CAD/CAM) model prepared from the computed tomography images for prosthetic/surgical diagnosis and treatment planning. RESULTS: The procedure of implant planning, model surgery, and sinus floor augmentation in this sophisticated flapless surgical approach has the potential to provide substantial benefits for both patients and practitioners. CONCLUSIONS: The versatility of the described technique not only allows more accurate implementation of the treatment plan to the patient's mouth but also may offer many additional significant benefits, including the use of custom surgical guides, life-sized bone model manipulation, and surgical rehearsal, all of which are very difficult to achieve with current traditional procedures. PMID- 20576336 TI - Genial tubercle fracture: a case report and review of the literature. PMID- 20576337 TI - Repair of whole rabbit facial nerve defects using facial nerve allografts. AB - PURPOSE: To investigate the feasibility of repairing whole facial nerve defects with chemically extracted acellular whole facial allografts nerves and its effect on motor conductivity recovery. MATERIALS AND METHODS: Whole nerve defects (branches and trunk) were made in 4 rabbit groups (n = 18), and the nerve defect was bridged using 1) acellular facial nerve allografts, 2) facial nerve isografts, 3) acellular peroneal nerve allografts, and 4) peroneal nerve isografts. Six months later, cell morphology, nerve microbeam distribution, angiogenesis, and collagen were observed in the distal and center of the grafts with special trichrome staining. The regenerated nerve fibers and Schwann cells in the anastomosis site were immunohistochemically stained. Nerve axon numbers and passing rates were analyzed with computer-captured images. The regenerated nerve ultrastructure was analyzed by transmission electron microscopy. RESULTS: Regenerated nerve fibers and vessels were found in the grafts, with no differences between groups A and B. Groups C and D had poor nerve continuity with little vascular regeneration. The distal segments of nerve transplants in groups A and B showed strong positive neurofilament staining, higher than in groups C and D. In groups A and B, many long spindle-shaped Schwann cells proliferated longitudinally in the nerve transplant, but less in groups C and D. Myelinated nerve fibers were found in the distal facial nerve. There were no differences between groups A and B in fiber number and myelin sheath thickness, which were much lower than normal, whereas little myelin sheath regeneration was observed in groups C and D. CONCLUSION: Chemically extracted acellular whole facial nerve allografts are feasible for repairing whole facial nerve defects. PMID- 20576338 TI - Soft tissue reduction during open treatment of intracapsular condylar fracture of the temporomandibular joint: our institution's experience. AB - PURPOSE: To evaluate the effect of soft tissue reduction during open surgery of intracapsular condylar fracture (ICF) of the temporomandibular joint (TMJ). MATERIALS AND METHODS: A total of 129 patients (164 TMJs) with ICF were treated from June 2004 to May 2009. Osteosynthesis was performed by different methods without stripping the lateral pterygoid muscle (LPM). The disc was reduced with or without transecting adhesions, release of the epimysium of the LPM, and anchorage to the condyle. Retrodiscal tissue tear was repaired. The patients were evaluated by computed tomography, magnetic resonance imaging, and clinical signs pre- and postoperatively. RESULTS: Inferomedial displacement of the condylar segment and disc occurred in 97.6% of cases. Adhesion of the superior joint space was found in 37 of 160 TMJs (23.1%). Retrodiscal tissue tear combined with disc displacement was found in 119 of 160 TMJs (74.4%). The condylar stump was found to be superolaterally displaced in 30.6% (49/160) and laterally dislocated out of the fossa in 41.9% (69/160). A lateral capsular tear was observed in 87 of 160 TMJs (54.4%). The condylar fragments and the discs were reduced and fixed completely with preservation of the attachment of the LPM. Coronal CT revealed that 95.6% (130/160 cases) of ICFs were correctly reduced and fixed. Postoperative magnetic resonance imaging showed that the disc was reduced to its normal position in 40 of 42 TMJs. Long-term complications of 45 patients included fibrous ankylosis in 1 case (0.8%), mouth opening limitation (<2.5 cm) in 5 cases, (3.9%), condyle resorption in 3 cases (2.3%) that needed plate removal, facial nerve injury in 3 cases (2.3%), TMJ click in 2 cases (1.6%), mouth open with deviation in 7 cases (5.4%), and malocclusion in 1 case (0.8%). CONCLUSION: Anatomic reduction of soft tissue was of benefit for biomechanical function of the TMJ and decreased the complications of open surgery. PMID- 20576339 TI - Acinic cell carcinoma of minor salivary glands: a clinicopathologic study of 21 cases. AB - PURPOSE: Acinic cell carcinoma (ACC) is an infrequent type of malignant salivary gland tumor. Approximately 16% of all ACCs occur in the mouth according to several small studies. This study was undertaken to 1) report on the clinicopathologic characteristics of 21 intraoral examples, 2) reconfirm the reported indolent behavior of these tumors, and 3) verify the synchronous or metachronous occurrence of other malignancies with ACC. MATERIALS AND METHODS: Twenty-one patients with intraoral ACC were identified in the previous 27 years. Demographic data and histomorphologic characteristics were evaluated and follow up information was sought. RESULTS: Fifteen patients (68%) were male and 6 female. Seven cases (33.3%) occurred in the buccal mucosa, 6 in the palate (28.6%), 5 involved the upper lip (23.8%), 2 the retromolar mucosa (9.5%), and 1 the lower lip (4.8%). The mean age of patients was 50 years, with the youngest being 13 and the oldest 73. The duration was known in 9 patients and varied from 4 months to longer than 15 years. The size of the tumors varied from 0.6 to 1.6 cm. Where reported, lesions were asymptomatic. Histologically, different patterns that included microcystic, papillary cystic, follicular and solid, and combinations of these types characterized the lesions. Follow-up information was obtained in 12 patients. Eleven patients did not report recurrence or metastatic disease. The follow-up extended from 10 months to 17 years. One patient had 2 recurrences due to erroneous diagnosis that led to inappropriate treatment. After properly diagnosed and treated, this patient has been free of tumor for 4 years. Of interest were the metachronous occurrence of lymphoma in 1 patient and the synchronous occurrence of renal cell carcinoma in another. CONCLUSION: This study confirms the indolent behavior of ACC of minor salivary glands and previous reports on the occasional synchronous or metachronous association of malignant salivary gland tumors with other malignancies. PMID- 20576340 TI - [Indications and compliance of home mechanical insufflation-exsufflation in patients with neuromuscular diseases]. AB - INTRODUCTION: Neuromuscular disease (NMD) patients frequently have impaired cough. Mechanical insufflation-exsufflation (MI-E) has proven efficacy in improving airway clearance, however data related to its long-term home use is lacking. The purpose of this study was to describe indications, safety and compliance of home MI-E in NMD patients. METHODS: Four years observational analysis of 21 NMD patients on home MI-E. Diagnosis included bulbar and non bulbar Amyotrophic Lateral Sclerosis (ALS) and other NMD. Median age was 58 years. Only cooperative patients with unassisted baseline Peak Cough Flow (PCF) <270 L/min were included. All patients were under continuous mechanical ventilation (6 by tracheostomy). Pulmonary function before initiation of MI-E (median): FVC=0.81 L, MIP=28cmH(2)O, MEP=22 cmH(2)O and PCF=60 L/min. MI-E was performed by previously trained non-professional caregivers, with an on-call support of a trained health care professional. Patients had pulse oximetry monitorization and applied MI-E whenever SpO(2)<95%. Median follow-up was 12 months (3-41 months). RESULTS: Ten patients (9 ALS) used MI-E daily. Eleven patients used MI-E intermittently, during exacerbations, and in 8 patients early application of MI-E (guided by oximetry feed-back) avoided hospitalization. All tracheostomized patients used MI-E daily and more times a day than patients under NIV. Four patients (3 bulbar ALS), were hospitalized due to secretion encumbrance. MI-E was well-tolerated and there were no complications. In general, caregivers considered MI-E effective. During this period, 4 patients died, related to disease progression. CONCLUSIONS: Home MI-E is well tolerated, effective and safe if used by well trained caregivers. MI-E should be considered as a complement to mechanical ventilation. PMID- 20576341 TI - [External assessment of the GEMA2009 recommendations by a multidisciplinary expert panel on asthma]. AB - OBJECTIVES: To assess the level of agreement on the GEMA 2009 clinical recommendations by a Spanish expert panel on asthma. MATERIALS AND METHODS: The study was divided into four stages: 1) establishment of a 9 member scientific committee (GEMA authors) for selection of GEMA recommendations to use in the survey; 2) formation of a panel of 74 professionals with expertise in this field (pulmonologists, allergists, family doctors, ear, nose and throat and paediatric specialists); 3) Delphi survey in two rounds, sent by mail, with intermediate processing of opinions and a report to the panel members; and 4) analysis and discussion of results for the Scientific Committee. RESULTS: Seventy four participants completed the two rounds of survey. During the first round, a consensus was reached in 49 out of 56 questions analysed. Following discussion by the panel, the consensus was increased to a total of 53 items in the survey. With respect to the remaining questions, Insufficient consensus was obtained on the rest of the questions, due to differing views between sub-specialists, or lack of criteria by most of the experts. CONCLUSIONS: The external analysis by asthma experts from different specialities showed a high level of professional agreement with the GEMA 2009 recommendations in Spain (96.5%). The disagreement shown in three recommendations reflect the lack of a high level evidence. These issues represent areas of interest for future research. PMID- 20576342 TI - Measuring potency of allergenic extracts. PMID- 20576343 TI - The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer. AB - OBJECTIVE: To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery. STUDY DESIGN: The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175mg/m2 on day 2, and IP paclitaxel 60mg/m2 on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period. RESULTS: The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p=0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy. CONCLUSIONS: Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery. PMID- 20576344 TI - Routine evaluation and treatment of unexplained menorrhagia: do we consider haemostatic disorders? AB - OBJECTIVE: Unexplained menorrhagia can be caused by underlying bleeding disorders. The aim of this study was to investigate the current work-up of menorrhagia in routine gynaecological practice, with a special interest in haemostatic evaluation. Secondly, we investigated the outcome of individualized treatment in our centre. STUDY DESIGN: Retrospective medical chart review of 112 consecutive patients referred with menorrhagia to a general gynaecology clinic of a university teaching hospital in the Netherlands between January 2006 and January 2007. In April 2008 we performed a structured telephone interview evaluating the effectiveness of their therapy. RESULTS: We included 112 patients, whose median age was 42 years. Twenty-nine percent were anaemic (hemoglobin <12.0g/dL). Seventy-one (63%) had unexplained menorrhagia. Only two patients had haemostatic evaluation and neither had von Willebrand's disease. Forty percent (29/71) needed two or more different therapies, 17% (12/71) needed three different therapies and two patients needed a total of seven different therapies. Eight patients underwent hysterectomy, six of them after endometrial ablation. Most patients (80%) were successfully treated medically or surgically and were satisfied with their therapy during follow-up. Eleven patients declined therapy and accepted their heavy periods. CONCLUSION: Haemostatic evaluation in women with unexplained menorrhagia is uncommon in gynaecological practice in our centre. Although most of the patients were satisfied with their treatment, a significant number required hysterectomy and another important proportion had to accept their menorrhagia. We hypothesize that the identification of haemostatic disorders might improve care for these women. PMID- 20576345 TI - The protective effect of erythropoietin and dimethylsulfoxide on ischemia reperfusion injury in rat ovary. AB - OBJECTIVES: The aim of this study was to investigate the effects of erythropoietin and dimethylsulfoxide in the recovery from ischemia-reperfusion injury in an experimental rat adnexal torsion model. STUDY DESIGN: Thirty-six Wistar-albino rats were divided into six groups. Except for the sham operation group, all groups were subjected to left unilateral adnexal torsion for 3h. Erythropoietin and dimethylsulfoxide were intraperitoneally administered 30min before the detorsion operation. Malondialdehyde and nitric oxide levels were detected from both the plasma and the tissue samples. The sections of the tissues were evaluated histologically. The results were analyzed by a one-way analysis of the variance (ANOVA) followed by the Duncan test for multiple comparisons using computer software, SPSS Version 15.0 for Windows. RESULTS: This study demonstrated that dimethylsulfoxide and erythropoietin pretreatment attenuated ischemia-reperfusion-induced lipid peroxidation, prevented post-ischemic ovarian injury and helped to maintain the ovarian morphology. Malondialdehyde levels of plasma and ovary were higher in the torsion and detorsion groups than the sham group. This showed that ischemia-reperfusion had caused lipid peroxidation of the ovarian tissue, thus leading to oxidative damage. One of the major findings of this study is that malondialdehyde was significantly decreased in the plasma of rats who were pre-treated with dimethylsulfoxide and erythropoietin before detorsion. This suggests that dimethylsulfoxide and erythropoietin might prevent oxidative damage in ovarian ischemia-reperfusion injury. Histological examination confirmed that reperfusion caused more detrimental effects than only ischemia, which could be at least partially prevented by dimethylsulfoxide and erythropoietin administration prior to detorsion. CONCLUSION: Erythropoietin and dimethylsulfoxide may have beneficial effects in ischemia-reperfusion injury in ovarian torsion. PMID- 20576346 TI - The prevalence of fecal incontinence and urinary incontinence in primiparous postpartum Chinese women. AB - OBJECTIVE: This study investigated the prevalence of fecal incontinence (FI) and urinary incontinence (UI) in primiparous postpartum Chinese women. STUDY DESIGN: Questionnaires about FI and UI symptoms were completed via telephone interviews conducted within 6 months postpartum. RESULTS: A total of 1889 primiparous postpartum women were asked to participate in this investigation. Only 13 (0.69%) of them had FI within 6 months after parturition, including loss of flatus in six women (0.32%), loss of solid stool in one (0.05%), loss of liquid stool in two (0.11%) and fecal urgency in four (0.21%). Bivariate logistic regression analysis showed that FI was significantly associated with forceps delivery OR=37.91 (95% CI 4.20-342.18, P=0.001) and medio-lateral episiotomy OR=11.79 (95% CI 1.47 94.46, P=0.02). The prevalence of UI, stress urinary incontinence (SUI), urge urinary incontinence (UUI) and mixed urinary incontinence (MUI) was 9.9% (186), 8.0% (151), 1.0% (18) and 0.9% (17), respectively. Multinomial logistic regression analysis found that SUI prevalence was related to age OR=1.08 (95% CI 1.04-1.12, P=0.000), maternal weight OR=1.04 (95% CI 1.02-1.06, P=0.001), neonate head circumference OR=1.17 (95% CI 1.01-1.36, P=0.043), spontaneous labor OR=5.42 (95% CI 2.60-11.32, P=0.000), forceps delivery OR=7.0 (95% CI 2.40-20.41, P=0.000), and medio-lateral episiotomy OR=5.24 (95% CI 3.15-8.72, P=0.000). CONCLUSIONS: 1. FI and UI prevalence was lower in our department than reported in previous studies in other areas. 2. Vaginal delivery has a risk impact on women's FI and UI, especially forceps delivery and medio-lateral episiotomy. 3. Maternal age, weight, newborn head circumference, spontaneous vaginal delivery, forceps delivery, and medio-lateral episiotomy increase the risk of UI. PMID- 20576347 TI - Formulating a coastal zone health metric for landuse impact management in urban coastal zones. AB - The need for ICZM arises often due to inadequate or inappropriate landuse planning practices and policies, especially in urban coastal zones which are more complex due to the larger number of components, their critical dimensions, attributes and interactions. A survey of literature shows that there is no holistic metric for assessing the impacts of landuse planning on the health of a coastal zone. Thus there is a need to define such a metric. The proposed metric, CHI (Coastal zone Health Indicator), developed on the basis of coastal system sustainability, attempts to gauge the health status of any coastal zone. It is formulated and modeled through an expert survey and pertains to the characteristic components of coastal zones, their critical dimensions, and relevant attributes. The proposed metric is applied to two urban coastal zones and validated. It can be used for more coast friendly and sustainable landuse planning/masterplan preparation and thereby for the better management of landuse impacts on coastal zones. PMID- 20576348 TI - A critique of visual materials in "Evidence for an occipito-temporal tract underlying visual recognition in picture naming". PMID- 20576350 TI - Microcalorimetric and potentiometric titration studies on the adsorption of copper by P. putida and B. thuringiensis and their composites with minerals. AB - In order to have a better understanding of the interactions of heavy metals with bacteria and minerals in soil and associated environments, isothermal titration calorimetry (ITC), potentiometric titration and equilibrium sorption experiments were conducted to investigate the adsorption behavior of Cu(II) by Bacillus thuringiensis, Pseudomonas putida and their composites with minerals. The interaction of montmorillonite with bacteria increased the reactive sites and resulted in greater adsorption for Cu(II) on their composites, while decreased adsorption sites and capacities for Cu(II) were observed on goethite-bacteria composites. A gram-positive bacterium B. thuringiensis played a more important role than a gram-negative bacterium P. putida in determining the properties of the bacteria-minerals interfaces. The enthalpy changes (DeltaH(ads)) from endothermic (6.14 kJ mol(-1)) to slightly exothermic (-0.78 kJ mol(-1)) suggested that Cu(II) is complexed with the anionic oxygen ligands on the surface of bacteria-mineral composites. Large entropies (32.96-58.89 J mol(-1) K(-1)) of Cu(II) adsorption onto bacteria-mineral composites demonstrated the formation of inner-sphere complexes in the presence of bacteria. The thermodynamic data implied that Cu(II) mainly bound to the carboxyl and phosphoryl groups as inner sphere complexes on bacteria and mineral-bacteria composites. PMID- 20576349 TI - All-trans retinoic acid downregulates ALK in neuroblastoma cell lines and induces apoptosis in neuroblastoma cell lines with activated ALK. AB - Recently, gene amplification and gain-of-function mutations of ALK have been found in some neuroblastoma cell lines and clinical tumor samples. We have previously reported that knockdown of ALK by RNAi induced apoptosis in neuroblastoma cells with gene amplification of ALK. We report that all-trans retinoic acid (ATRA) downregulates ALK in neuroblastoma cell lines. Downregulation of ALK protein by ATRA was accompanied by apoptosis in neuroblastoma cells with gene amplification or gain-of-function mutation of ALK but not in neuroblastoma cells without these genetic alterations. These results suggest that ALK downregulation by ATRA might lead to apoptosis in neuroblastoma cells with activated ALK. PMID- 20576351 TI - Aqueous 4-nitrophenol decomposition and hydrogen peroxide formation induced by contact glow discharge electrolysis. AB - Liquid-phase decomposition of 4-nitrophenol (4-NP) and formation of hydrogen peroxide (H(2)O(2)) induced by contact glow discharge electrolysis (CGDE) were investigated. Experimental results showed that the decays of 4-NP and total organic carbon (TOC) obeyed the first-order and pseudo-first-order reaction kinetics, respectively. The major intermediate products were 4-nitrocatechol, hydroquinone, benzoquinone, hydroxyhydroquinone, organic acids and nitrite ion. The final products were carbon dioxide and nitrate ion. The initial formation rate of H(2)O(2) decreased linearly with increasing initial concentration of 4 NP. Addition of iron ions, especially ferric ion, to the solution significantly enhanced the 4-NP removal due to the additional hydroxyl radical formation through Fenton's reaction. A reaction pathway is proposed based on the degradation kinetics and the distribution of intermediate products. PMID- 20576352 TI - Biodecolorization of Acid Red GR by a newly isolated Dyella ginsengisoli LA-4 using response surface methodology. AB - Decolorization of Acid Red GR by a newly isolated biphenyl-degrading bacterium, Dyella ginsengisoli LA-4 was presented in this paper. The optimal decolorization conditions were determined by response surface methodology (RSM) based on the rotatable central composite design. The results indicated that strain LA-4 possessed the highest decolorizing activity under anaerobic conditions with inoculation amount 6.49%, pH 7.06 and temperature 29 degrees C. Some ions such as Cu(2+), Zn(2+) could inhibit the decolorization, whereas 1 mmol/L of Mg(2+), Ca(2+), Co(2+), Fe(3+), Ni(2+) and Mn(2+) had no effects on the process. It was demonstrated that anthraquinone as a redox mediator could significantly accelerate the reduction process of azo dyes. PMID- 20576353 TI - Synthesis of monoclinic structured BiVO4 spindly microtubes in deep eutectic solvent and their application for dye degradation. AB - Monoclinic structured spindly bismuth vanadate microtubes were fabricated on a large scale by a simple ionothermal treatment in the environment-friendly green solvent of urea/choline chloride. The as-prepared samples were characterized by XRD, SEM, TEM, IR and their photocatalytic activity was evaluated by photocatalytic decolorization of rhodamine B aqueous solution under visible-light irradiation. As-obtained BiVO(4) microtubes exhibit the spindly shape with a side length of ca. 800 nm and a wall thickness of ca. 100 nm. The opening of these microtubes presents a saw-toothed structure, which is seldom in other tube-shaped materials. The formation mechanism of the spindly microtubes is ascribed to the complex cooperation of the reaction-crystallization process controlled by BiOCl and the nucleation-growth process of nanosheets induced by solvent molecules attached on the surface of microtubes. Such spindly microtubes exhibit much higher visible-light photocatalytic activity than that of bulk BiVO(4) prepared by solid-state reaction, possibly resulting from their large surface area and improved crystallinity. PMID- 20576354 TI - MAFRAM- a new fate and risk assessment methodology for non-volatile organic chemicals. AB - The main goal of this paper was to introduce an environmental fate and risk assessment methodology for comparing and establishing the general features of new and existing non-volatile organic chemicals (NVOCs) used in agricultural activities, based on simple and readily available properties. This methodology is a computer program called the multimedia agricultural fate and risk assessment model (MAFRAM). This model is a combination of the EQC-2V model, which describes the fate of NVOCs, with the ecological relative risk (EcoRR) approach, which assesses the ecotoxicological risk to agro-ecosystems. MAFRAM divides the agricultural environment into two main zones, which are the on- and off-farm zones. Each zone is subdivided into six compartments, including the air, water, soil, sediment, aboveground plants, and roots. The required input data are the chemical-physical properties of the pesticide, biota data, and environmental properties. The MAFRAM output includes the inter-compartmental transport and transfer rates, the primary loss mechanisms, chemical concentration, amount, residence time, and the rank of risk in each compartment. In addition, it can provide several secondary results. The MAFRAM application was illustrated using typical homogenous region properties and was run with an illustrative emission rate of 1 kg/h into air, using spinosad as a case study. PMID- 20576355 TI - Active carbons prepared by chemical activation of plum stones and their application in removal of NO2. AB - A technology of obtaining active carbon from plum stones by chemical activation with KOH is described. The effect of carbonisation temperature as well as activation procedure on the textural parameters, acid-base character of the surface and sorption properties of active carbons has been checked. The sorption properties of the activated carbons obtained were characterised by determination of nitrogen dioxide adsorption in dry and wet conditions. The final products were microporous activated carbons of well-developed surface area varying from 2174 to 3228 m(2)/g and pore volume from 1.09 to 1.61 cm(3)/g, showing different acid base character of the surface. The results obtained in our study have proved that a suitable choice of the carbonisation and activation procedure for plum stones can produce activated carbons with high capacity of nitrogen dioxide, reaching to 67 and 42 mg NO(2)/g in dry and wet conditions, respectively. The results of our study have also shown that the adsorption ability of carbonaceous sorbents depends both on the method of preparation as well as on the textural parameters and acid-base properties of their surface. PMID- 20576357 TI - Fluid resuscitation in burns. PMID- 20576358 TI - Ocular burns and related injuries due to fireworks during the Aidil Fitri celebration on the East Coast of the Peninsular Malaysia. AB - This study aims to describe the epidemiology of ocular burns and related injuries due to fireworks during the Aidil Fitri celebration on the East Coast of the Peninsular Malaysia. A prospective analysis of all patients with ocular burns and related injuries due to fireworks attended three tertiary hospitals in East Coast of Peninsular Malaysia during Aidil Fitri, which was from 10 September to 17 October 2008. We observed the demographic and injury characteristics, extent of the injuries and presenting visual symptoms. Thirty patients with 34 eyes with ocular burns and related injuries were identified. Patients ranged between 2 and 43 years of age. 70.00% of the patients were 12 years old and below. Of the 30 patients, 29 (96.67%) were male and the left eye was affected in 14 (46.70%). Thermal injuries accounted for 60.0% of the injuries whereas 40.0% were due to exploding firework. Burns to the eyelid and cornea (35.29%) were the most common injuries noted. Fifteen patients (50%) were bystanders whilst a majority of patients (96.67%) had no eye protection. At presentation, 15 (44.12%) eyes had a visual acuity of 6/6 to 6/9 in the injured eyes, while 3 out of 34 eyes (8.82%) had vision acuity 6/60 or worse. In conclusion, fireworks cause serious preventable ocular burns and related injuries especially in children who are the most affected age group. It affects mainly eyelid and anterior segment structures which result in moderate visual loss on presentation. Health education, public awareness and tighter legislation are essential preventive measures to limit the effect of fireworks to the public. PMID- 20576359 TI - Emotional associations with skin: differences between burned and non-burned individuals. AB - INTRODUCTION: The appearance of skin is crucial for our physical and psychological integrity, and is strongly associated with our emotional self awareness. Burn victims have to cope with negative and even threatening sensations resulting from the changed appearance of their skin after injury and also linked to experiences during the treatment. The aim of this study was to analyse differences regarding the emotional associations with skin in burn victims (burn group) to persons not having subdued any burn (control group). METHODS: In the first instance over 960 volunteers were recruited for the rating of emotional associations with skin in the control group and thereby a representative profile for non-injured individuals. In the second part, 44 burn patients of the Vienna Burn Center answered the same questionnaire. The quantitative rating of emotional associations with skin was performed with a newly designed questionnaire using a semantic differential on eight dimensions with a 5-point scale system. RESULTS: Both groups have positive associations with skin. One significant difference (p=0.0090, Chi-square test for trend) was the overall rating of the item "importance": for burn victims skin is more "important" than for controls. Patients with visible burns tended to put more emphasize on the possible exposure to danger ("threatened") of skin, and patients with >/=20% TBSA rated skin as more "noticeable" and "strong" as compared to small burns (<20% TBSA). Patients with burns to the face, hands and neck ("visible burns") were more likely to judge skin as threatened item. DISCUSSION: Our poll suggests that despite long treatment, rehabilitation and even near-death experiences burn patients continue to have positive associations with skin. This in turn, should encourage all specialists dealing with burns to engage in a continuous follow-up as well as enhance psychological and social support. PMID- 20576360 TI - A role for glucocorticoids in the long-term establishment of a social hierarchy. AB - Stress can affect the establishment and maintenance of social hierarchies. In the present study, we investigated the role of increasing corticosterone levels before or just after a first social encounter between two rats of a dyad in the establishment and the long-term maintenance of a social hierarchy. We show that pre-social encounter corticosterone treatment does not affect the outcome of the hierarchy during a first encounter, but induces a long-term memory for the hierarchy when the corticosterone-injected rat becomes dominant during the encounter, but not when it becomes subordinate. Post-social encounter corticosterone leads to a long-term maintenance of the hierarchy only when the subordinate rat of the dyad is injected with corticosterone. This corticosterone effect mimics previously reported actions of stress on the same model and, hence, implicates glucocorticoids in the consolidation of the memory for a recently established hierarchy. PMID- 20576361 TI - Noradrenergic function and HPA axis dysregulation in suicidal behaviour. AB - Noradrenergic and HPA axis dysregulation may play a role in suicide risk. Studies of suicide risk have not found consistent relationship to the noradrenaline metabolite 3-methoxy-4-hydroxphenylglycol (MHPG) in the cerebrospinal fluid (CSF). Non-suppression in the dexamethasone test (DST) has been associated with increased risk of suicide in depressed patients. The study sample consisted of 51 mood disorder inpatients admitted to the Department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. Patients underwent lumbar punction and DST and were followed up for the cause of death. The hypothesis was that both CSF MHPG and HPA axis dysregulation are associated with suicidal behaviour. Nine suicide victims had significantly lower CSF MHPG and baseline plasma cortisol than survivors. Using both CSF MHPG and baseline cortisol in ROC analysis for suicide prediction, the positive predictive value was 44% and the area under the curve was 0.88. In conclusion, lower CSF MHPG was associated with suicide risk. Furthermore these results suggest that combined measures of noradrenergic system and HPA axis function may offer better prediction of suicide risk. PMID- 20576362 TI - Do thyroid hormones mediate the effects of starvation on mood in adolescent girls with eating disorders? AB - In the eating disorders (ED) comorbid depression is common and clinical experience suggests that it is partly related to starvation. Starvation affects thyroid hormone status and thyroid hypofunction is in turn associated with depressed mood. We have therefore investigated the possibility that thyroid hormones and starvation are associated with mood in ED. Two-hundred and thirty nine adolescent girls were examined at presentation of an ED. Analyses of thyroid hormones, documentation of weight and weight changes, self-reports of depressive symptomatology and clinical diagnoses of ED and depression were used in the analyses. Of the 239 girls 100 were diagnosed with depression. The girls with and without depression did not differ in age, weight, height, body mass index (BMI), weight loss or duration of disease. Plasma free thyroxine concentrations were lower in depressed girls (11.9+/-1.7 versus 12.8+/-1.9 pmol/L; p<0.01). Plasma triodothyronine and thyroid-stimulating hormone concentrations did not differ between groups. In a logistic regression analysis the odds ratio for depression was 41.1 (95% confidence interval 4.18-405; p=0.001) for a 10 pmol/L change of plasma free thyroxine after correction for BMI, weight loss, duration of disease, rate of weight loss, plasma triodothyronine and an interaction between BMI and plasma free thyroxine. BMI did not predict depression. Low circulating thyroxine concentrations may provide a link between starvation and depression in adolescent girls with ED. PMID- 20576363 TI - [Evaluation of a proximity training program of nuchal translucency measurements and of self-scoring]. AB - OBJECTIVE: Improvement in prenatal diagnosis of Down syndrome imposes to sonographers to realize good quality nuchal translucency measurements, which can be used for assessment of combined risk. The aim of our study was to evaluate a training program of 109 sonographers for measuring nuchal translucency and scoring their own image. STUDY DESIGN: After a proximity training program, trainees submitted 20 images scored by themselves with Herman image-scoring method. All images were reviewed by two experts. RESULTS: One hundred and nine sonographers have accomplished the training program (87.3%), collecting 2162 images. After reviewing, the mean score was 6.8+/-1.8. The rate of inacceptable scan (score< or =3) was in 6.0%. On the other hand, 48.1% of scans were excellent (score> or =8). Only 6.5% of scores were discordant for at least three points between self-scoring and reviewing. After the fourth scan, there was no significant scoring difference between self-scoring and reviewing. Finally, 84% of trainees were very satisfied of this program. CONCLUSION: As part of HAS evaluation of practitioners practices, it is possible to realize proximity training program for measuring nuchal translucency. Learning curve seems to be fast. Good handling of Herman scoring method by sonographers allows their accreditation after this kind of training program. PMID- 20576365 TI - Gender and NAS: does sex matter? AB - BACKGROUND: Neonatal abstinence syndrome (NAS) is a constellation of symptoms resulting from in utero exposure to opioids that appears in 30-80% of opioid exposed infants. Variability in NAS symtomatology is not well understood, and recently it has been suggested that the sex of the infant may play a role in predicting NAS severity. The current study examines the relationship of sex to need for NAS treatment, length of NAS treatment, and peak dose of medication required to treat NAS symptoms. METHODS: Retrospective chart review of 308 infants was conducted to determine whether significant differences exist between male and female neonates in need for NAS treatment, length of treatment and peak dose of medication required. Chi-square, multiple ordinary least squares regression, and analysis of variance (ANOVA) analyses were conducted. RESULTS: No significant differences were found in need for NAS treatment, length of treatment or peak dose of medication required between male and female neonates. CONCLUSIONS: Results suggest that no significant differences exist in NAS severity between male and female infants. PMID- 20576367 TI - Gene expression analysis in distinct regions of the central nervous system during the development of SSBP/1 sheep scrapie. AB - Rodent scrapie models have been exploited to define the molecular basis for the progression of neuropathological changes in TSE diseases. We aim to assess whether CNS gene expression changes consistently observed in mouse models are of generic relevance, for example to natural TSE diseases, or are TSE strain, host species or brain region specific. Six genes, representing distinct physiological pathways and showing consistent changes in expression levels with disease progression in murine scrapie models were analysed for expression (RT-qPCR) in defined regions of the sheep brain at various times after SSBP/1 scrapie infection. Gene expression was examined in relation to the development of neuropathological changes including PrP(Sc) deposition and vacuolation. Peripheral infection of sheep with SSBP/1 showed consistent progression of neuropathology as assessed by the temporal course of PrP(Sc) deposition and neuropil vacuolation. The first region affected was the medulla (obex), then the thalamus and finally the cerebellum and frontal cortex. In contrast to mouse scrapie, there were few significant changes in transcript expression for any of the six genes and no consistent changes in patterns of expression in relation to brain region, time after infection or neuropathology in sheep SSBP/1. Gene expression changes in mouse TSE models, even changes consistent with the neuropathology, cannot necessarily be extrapolated to species in which disease naturally occurs. This may represent differences in pathological processes of different scrapie strains or across species; and highlights the difficulties in identifying generic molecular pathways associated to the pathogenesis of TSE disease. PMID- 20576366 TI - Dairy cows with metritis: Coxiella burnetii test results in uterine, blood and bulk milk samples. AB - In cattle, Coxiella burnetii infections are generally asymptomatic but can also be associated with reproductive disorders. Metritis is considered as one of the symptoms of C. burnetii infections, but reliable information is lacking. Therefore, information on the presence of C. burnetii in the uterine content of cows with metritis is important to increase our knowledge on this pathogen. In this study, the uterine content of 45 dairy cows with metritis belonging to 12 herds was tested for C. burnetii with a real-time PCR assay. Only one uterine sample tested PCR (highly) positive, all other samples were PCR negative. The PCR positive cow tested also positive for antibodies. Three other cows from other herds tested antibody positive. The bulk milk (BM) samples of these 12 herds were tested by real-time PCR assay and antibody-ELISA. Six BM samples (50%) were positive in PCR and 10 (83%) were positive in ELISA. Culturing the uterus samples by bacteriology, the most frequently cultured bacteria were arcanobacterium (n=24), E. coli (n=16), other streptococci (n=10), Streptococcus uberis (n=8) and Streptococcus dysgalactiae (n=5). This study indicates that C. burnetii is not an important cause for metritis in dairy herds, although apparently C. burnetii was or had been present in most of these herds. PMID- 20576364 TI - Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults. AB - OBJECTIVE: This study compared the acute phase (12-week) efficacy of fluoxetine versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid major depression (MDD) and a cannabis use disorder (CUD) (cannabis dependence or cannabis abuse). We hypothesized that fluoxetine would demonstrate efficacy versus placebo for the treatment of the depressive symptoms and the cannabis use of adolescents and young adults with comorbid MDD/CUD. METHODS: We conducted the first double-blind placebo-controlled study of fluoxetine in adolescents and young adults with comorbid MDD/CUD. All participants in both treatment groups also received manual based cognitive behavioral therapy (CBT) and motivation enhancement therapy (MET) during the 12-week course of the study. RESULTS: Fluoxetine was well tolerated in this treatment population. No significant group-by-time interactions were noted for any depression-related or cannabis-use related outcome variable over the 12 week study. Subjects in both the fluoxetine group and the placebo group showed significant within-group improvement in depressive symptoms and in number of DSM diagnostic criteria for a CUD. Large magnitude decreases in depressive symptoms were noted in both treatment groups, and end-of-study levels of depressive symptoms were low in both treatment groups. CONCLUSIONS: Fluoxetine did not demonstrate greater efficacy than placebo for treating either the depressive symptoms or the cannabis-related symptoms of our study sample of comorbid adolescents and young adults. The lack of a significant between-group difference in these symptoms may reflect limited medication efficacy, or may result from efficacy of the CBT/MET psychotherapy or from limited sample size. PMID- 20576368 TI - Management of the vulnerable baby on the postnatal ward and transitional care unit. AB - Many guidelines for the prevention and management of neonatal hypoglycaemia focus on the sick infant admitted to the intensive care unit and pay scant attention to what is known about normal neonatal physiology. It is questionable whether treatment guidelines for low blood glucose levels for sick infants can be applied to a population of well infants on the postnatal ward, especially if such guidelines interfere with the establishment of breastfeeding, which has well recognised long and short term health benefits for mother and baby. What then of the baby who is at risk of abnormal postnatal adaptation, but is not unwell? Can the complications which occur in such infants, such as hypoglycaemia, be safely managed without resorting to admission to a baby unit? Can such vulnerable infants be safely managed in an environment that promotes mother and baby bonding and facilitates breastfeeding? PMID- 20576369 TI - Intrauterine growth restriction in a low-income country: Risk factors, adverse perinatal outcomes and correlation with current WHO Multicenter Growth Reference. AB - OBJECTIVE: To determine risk factors and adverse perinatal outcomes including nutritional status in the first week of life for newborns with intrauterine growth restriction-low birth weight (IUGR-LBW) in settings lacking facilities for routine intrauterine growth monitoring. METHODS: A cross-sectional study of all infants in an inner-city hospital in Lagos, Nigeria. IUGR-LBW was defined as full term (gestational age> or =37 weeks) infant with low birth weight (<2500g). Nutritional/growth status at enrolment was determined by z-scores for length-for age (HAZ), head circumference-for-age (HCZ), weight-for-age (WAZ) and weight-for length (WHZ) based on current World Health Organization's Multicentre Growth Reference (WHO-MGR). Factors and adverse outcomes associated with IUGR-LBW were explored with multivariable logistic regression analyses. RESULTS: Some 145 (4.3%) infants were IUGR-LBW out of 2619 eligible singletons enlisted for this study. IUGR-LBW was significantly associated with teenage mothers (OR:2.90, 95% CI:1.22-6.89), lack of antenatal care (OR:1.88, 95% CI:1.33-2.65) and female gender (OR:1.38, 95% CI: 0.98-1.93; p=0.062). The incidence of adverse outcomes across gestational age showed significant linear trend only for low five-minute Apgar scores (p=0.024) and WAZ (p=0.065). IUGR-LBW was associated with poor nutritional status across all four indices (p<0.001) as well as low 5-minute Apgar scores (p=0.095), sepsis (p=0.053), hyperbilirubinemia (p<0.001) and admission into special care baby unit (p=0.009) after multivariable logistic regression analyses. CONCLUSIONS: IUGR-LBW correlates with poor nutritional status in the first week of life based on WHO-MGR and affected infants can be detected early for effective surveillance in resource-poor settings. Improved prenatal care among teenage mothers is necessary for reducing IUGR-LBW burden. PMID- 20576370 TI - Forensic and police identification of "X" bodies. A 6-years French experience. AB - The identification of X bodies is an everyday preoccupation in forensic pathology. This retrospective analysis studied all methods of identification and characteristics of unidentified bodies arrived in the Department of Forensic Medicine and Pathology (University Hospital R. Poincare, Garches, France) during a 6-years period (2003-2009). The aim was to determine the identification methods used during all the forensic investigations, but also to study causes and manner of death in this sample of the population. A total of 9.1% of all autopsies were on X cadavers (217 cases out of 2384). On this total, only 134 of them have been included in our series after exclusion of archaeological and animal samples, but also of unidentified individuals or incomplete data available. Almost 28% of them have been identified with molecular biology (DNA), 23% with odontological examination, 7.5% with fingerprinting and 6.7% with autopsy data. Manner of death was mainly suicide (40.3%) especially by asphyxia following drowning, then accidental death (17.9%) especially consecutive to multiple trauma after traffic accident, acute carbon monoxide intoxication or carbonization in a fire. A total of 11.9% natural deaths were found (50% of them being of cardio-vascular origin) and 11.2% of homicides (with the use of firearm in a third of them). For 18.7% of X cadavers, the mode of death was undetermined. 46.4% of all unidentified bodies in our series were only identified by the police investigations, using physical recognition (direct or with photographs) or personal effects or identity documents in close relationship with the body. Our study highlights the fact that quite half of all unidentified bodies are inhumed with an identity not scientifically proved. Bodies which remained unidentified after all investigations represent 10.2% of X cadavers (if we consider a group of 176 cases composed of our study sample of 134 cases plus 24 subjects identified just before the autopsy and the 18 cases which remained unidentified) and 0.8% of all autopsies performed in the department. PMID- 20576371 TI - Detecting gravesoil with headspace analysis with adsorption on short porous layer open tubular (PLOT) columns. AB - Victims of crimes are often buried in clandestine graves. There are several techniques for finding buried bodies or the scattered remains of a victim; however, none of these methods are very reliable or work in all scenarios. One way to detect gravesoil is to detect the biochemical changes of the surrounding soil due to cadaver decomposition, for example, the release of nitrogenous compounds. A simple and low-cost way to detect these compounds is based on the reaction of alpha amino groups with ninhydrin to form Ruhemann's purple. This test for ninhydrin-reactive nitrogen (NRN) has, to date, only been performed by direct solvent extraction of soil samples. Here, we present a method that detects trace quantities of NRN in the headspace air above gravesoil. Our method is based on an improved purge and trap method developed in our lab for sampling low volatility compounds, as well as volatile compounds at trace quantities, by applying low temperature collection on short alumina-coated porous layer open tubular (PLOT) columns. We modified this method to sample the headspace air above gravesoil with a motorized pipetter and a PLOT column at ambient temperatures. We generated gravesoil using rat cadavers and local soil. Trace quantities of NRN were successfully detected in the headspace air above gravesoil. We report the quantities of NRN recovered for buried rats, rats laid on top of soil, and blank graves (no rats) as a function of time (weeks to months). This work is the first (and thus far, only) example of a method for detecting NRN in the vapor phase, providing another tool for forensic investigators to aid in locating elusive clandestine graves. PMID- 20576372 TI - Predictive factors for the outcome of nasal septal perforation repair. AB - OBJECTIVES: The aim of this study was to determine the important predictive factors for successful repair of nasal septal perforation. MATERIALS AND METHODS: In this study, we examined 35 symptomatic patients (27 males and 8 females, aged from 16 to 76 years) with a nasal septal perforation. In order to correlate pre- and intra-operative factors to the respective results, preoperative symptoms, etiologies, size of the perforation, operation methods and postoperative results from the patients were reviewed and analyzed using logistic regression. RESULTS: Nasal obstruction, crust and epistaxis were common preoperative symptoms. In most cases, perforations were observed to evolve after the patients' trauma caused from their previous nasal surgery experience. The overall reperforation rate was 48% and turned out to be associated with both large perforation size and unilateral mucosal flap coverage. However, we found no strong evidence that other factors such as graft materials and medical conditions were related with surgical failure. The surgical operations for our examinees resulted in complete healing of epistaxis and whistling, whereas nasal obstruction and crusting persisted after the surgeries. In addition, symptom improvement was negatively correlated with large perforation size and nasal trauma history including previous nasal surgeries. CONCLUSION: Precise and complete coverage with bilateral flaps might be the most important factor for successful closure in a septal perforation. Moreover, both trauma history and large perforation size might be at risk for persistent symptoms after septal perforation repair. PMID- 20576373 TI - Auditory function in patients with systemic lupus erythematosus. AB - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) may develop hearing and balance disorders as a result of the immune-mediated inner ear damage due to vasculitis or ototoxicity of drugs used in SLE treatment. The aim of the study was evaluation of the hearing organ disorders in patients with SLE with particular regard to their prevalence and relationship to duration and severity of disease. The severity was assessed from involvement of organs that resulted in poorer SLE outcome, i.e. kidneys and central nervous system (CNS), and from the presence of antibodies associated with unfavourable SLE prognosis. METHODS: Thirty-five unselected, consecutive patients (33 women, two men, mean age 47.8 years) with SLE diagnosed in compliance to the international diagnostic criteria of the American Rheumatism Association (1982) were enrolled into the study. The control group consisted of 30 otologically healthy persons matched to the SLE group for age and sex. Case history was recorded for all patients from questionnaire data and laryngological examinations were performed, followed by pure-tone, speech and impedance audiometry and auditory brainstem response audiometry (ABR). RESULTS: In the anamnesis 71.4% of patients reported vertigo, 62.9% headaches, 40% tinnitus, 25.7% hyperacusis, 17.1% hearing loss and 2.9% ear fullness. It was found that SLE patients had a significantly poorer mean hearing thresholds than the control group for all frequencies, except for 500; 2000 and 4000 Hz. Longer ABR latency averages were observed in the group of SLE patients compared to control. Ten patients (28.6%) developed high-frequency and symmetric sensorineural hearing loss (SNHL). Significant positive correlation between mean air-conduction hearing thresholds and SLE duration (r = 0.46, p < 0.001) was found. After taking age into consideration, hearing acuity in SLE was related to duration of disease in younger patients. Furthermore, no relation was seen between hearing level and severity of disease. CONCLUSIONS: Auditory system involvement ought to be considered as one of elements of the clinical picture of systemic lupus erythematosus while determination of its character, original or secondary, requires further research. PMID- 20576374 TI - Foreign body aspiration, a continuously growing challenge: Tanta University experience in Egypt. AB - OBJECTIVE: To evaluate the different factors that affect the spectrum and frequency of foreign body (FB) aspiration as a growing problem in different ages, and express the experience of our department in managing the problem in the recent two decades. METHODS: The charts of 3600 patients who underwent bronchoscopic evaluation over a period of 20 years for a suspicion of FB inhalation were reviewed. The patients were divided according to the age into group A; up to 10 years, and group B; more than 10 years. Each group was investigated and compared with the other with respect to sex, history of FB aspiration, time elapsed between aspiration and hospital admission, clinical and radiographic findings, and FB location, type, retrieval, and complications. Seasonal, geographic, and socio-cultural factors and frequency of FB aspiration in relation to the study period were also recorded. RESULTS: In group A, boys were affected more than girls (1.3:1), while in group B, females were affected more than males (40.5:1). Among history positive patients in group A (72.8%) and B (96.8%), FB was detected in 88% and 97% respectively, while among history negative patients, FB was found higher in group A (49%) than group B (25%). The time elapsed before admission was longer in group A than group B. Cough was the most prominent symptom, while decreased breath sounds was the commonest sign in both groups. Pneumatic infiltration was the most frequent radiographic finding in group A (33.6%), while radio-opaque FB was higher in group B (94.1%). Peanut (67.3%) and seeds (21.2%) were the commonest FBs detected in group A, whereas, headscarf pins (91.3%) were predominant in group B. Foreign bodies were almost equally distributed in the laryngotracheobronchial tree in group A, while the left bronchial tree was much more affected in group B. Rigid bronchoscopy was used in groups A and B with a success rate of 99.8% and 99.7% respectively, while flexible bronchoscopy was only used in 0.2% in group B. Complications such as laryngotracheal edema (16.6%) and pneumothorax (2.3%) were encountered in group A more than group B (3.1%, 1.2%) and there was no mortality. Most of the aspirated FBs were recorded during summer months and commonly detected in patients of low socio-cultural status in both groups. CONCLUSION: Foreign body aspiration is a continuously growing problem in Lower Egypt affecting all ages with two peaks at 3 and 14 years old. The rate of FB aspiration was affected by age; sex; traditions and believes; and seasonal, geographic, and socio-cultural factors. A high index of suspicion, rapid hospital admission, and bronchoscopic evaluation by experienced specialists were crucial for successful retrieval of the FB with low rate of morbidity. Public awareness through mass media needs attention to decrease the growing rate of this problem. PMID- 20576375 TI - Cochlear implantation in a patient with atypical Cogan's syndrome complicated with hypertrophic cranial pachymeningitis. AB - A 55-year-old woman had bilateral sensorineural hearing loss (SNHL), vertigo, uveitis, and aortitis associated with Cogan's syndrome (CS). She had a history of listeria meningitis and hypertrophic cranial pachymeningitis (HCP), both of which were considered to be related to SNHL progression. She developed bilateral profound deafness within 1 year, despite medical treatment with corticosteroids and methotrexate (MTX). She underwent cochlear implantation (CI) of the left ear. Although the left and right basal turns of the cochleae were ossified, all electrodes were successfully inserted, and subsequently the inferior segment of the basal turn was drilled out. The patient did not have any postoperative complications and showed good speech perception. PMID- 20576376 TI - A spontaneous true aneurysm of the superficial temporal artery treated by surgical resection. AB - An aneurysm of the superficial temporary artery (STA) has a rarer occurrence than intracranial aneurysm. However, traumatic aneurysms of the STA are not unusual and have been reported about more than 400 cases. Most of these were pseudoaneurysms caused by blunt trauma because of the anatomical location of STA. In contrast, spontaneous or non-traumatic aneurysms of the STA are quite rare and only 8 cases of spontaneous true aneurysms in the STA have been reported. Herein, we report a case of a 77-year-old woman, who presented with a preauricular mass showing subacute enlargement over the previous two months. She had no history of head injury. Imaging studies demonstrated that the mass was a saccular type aneurysm accompanied by afferent and efferent vessels. The mass was resected under general anesthesia and there were no symptoms or signs of local circulatory deficiency, nor was there any interference with nerve function after the surgery. Pathological examination showed that the mass was a true aneurysm. The literature is reviewed and the management of the STA aneurysm is discussed. PMID- 20576377 TI - Bile secretion. PMID- 20576378 TI - Hereditary haemorrhagic telangiectasia. PMID- 20576379 TI - Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study. PMID- 20576380 TI - Back to basics for idiosyncratic drug-induced liver injury: dose and metabolism make the poison. AB - Two studies show that the risk of drug-induced liver injury (DILI) is increased when the daily dose of a drug given by oral route is higher than 10mg per day and/or when the drug undergoes a significant hepatic metabolism. If confirmed, these data suggest that developing drugs with high potency and low hepatic metabolism will reduce the risk of idiosyncratic DILI in man. PMID- 20576381 TI - Nutcracker esophagus: an acid related disease or a primary motor disorder? PMID- 20576382 TI - Our perspective on endoscopic resection for colorectal neoplasms. AB - Endoscopic mucosal resection (EMR) is a minimally invasive technique for effective treatment of early stage colorectal lesions with no invasive potential. However, the high frequency of local recurrence after piecemeal EMR for large lesions is considered a serious problem. In contrast, endoscopic submucosal dissection (ESD) allows en-bloc resection, irrespective of the lesion's size. ESD has been established as a standard method for the endoscopic removal of early cancers in the upper gastrointestinal tract in Japan. Although the use of ESD for colorectal lesions has been studied clinically, ESD is not yet established as a standard therapeutic method. We define the indications for en-bloc resection, based on extensive clinicopathological analyses, as a laterally spreading tumor (LST) non-granular type (LST-NG) lesion greater than 20 mm and an LST granular (LST-G) type lesion greater than 40 mm. Both of these lesions had a high submucosal invasion rate. Especially, LST-NG type lesions greater than 20 mm are technically difficult to remove completely even by piecemeal EMR and are considered a "definite indication for en-bloc resection". The ESD procedure is undoubtedly an ideal method to achieve en-bloc resection, however, the prevalences of suitable lesions among all neoplastic lesions and among all early cancers were not high (1.0% and 5.0%, respectively). Therefore, it is crucial to master more fundamental therapeutic techniques and have knowledge of surveillance strategy after endoscopic treatment. PMID- 20576383 TI - Sonographic diagnosis features of Zenker diverticulum. AB - OBJECTIVE: The purpose of this study was to analyze the image of the lesion and give the sonographic diagnosis features of Zenker diverticulum. METHODS: Sonography was performed with a high-frequency linear array probe. The location, size, shape, and echogenicity of the Zenker diverticulum were recorded. To find the lesion whether to be connected with the adjacent esophageal wall. During compressing with a probe, to detect the changes of the lesion shape and echogenicity. As swallowing or drinking water, to detect the fluid whether to enter into the lesions. All patients were given barium swallow test. RESULTS: All nine Zenker diverticulum were all located at the posterolateral aspect of the left lobe. The long diameters of all Zenker diverticulum measured by sonography ranged from 9.6mm to 45 mm (average 16.4+/-11 mm). There were four types of sonogram features of Zenker diverticulum in our study: (1) The lesion was isoechoic mass with boundary hypoechoic rim and internal small, punctuate, echogenic foci. (2) The lesion contained a central hyperechoic area associated with a comet-tail artifact. (3) The lesion was hyperechoic and heterogeneous, with stronger echoes anteriorly, but there was no acoustic shadowing or reverberation artifacts. (4) The lesion was oval-shaped mixed nodule, with unclear border and relatively multiple punctuate strong echoes. During the patient's ingestion of water, an increase in the lesion's size, a reduction in the definition of the margins, and heterogeneous echogenicity of the lesion's contents are observed. Barium-swallow images of the upper esophagus demonstrate an out-pouching at the posterior aspect of the pharyngoesophageal junction. CONCLUSION: The sign of air in the Zenker diverticulum is the most important sonographic feature for differential diagnosis from thyroid nodules. It was useful to diagnosis and prevents patients from invasive procedure such as aspiration and unnecessary operation. PMID- 20576384 TI - Diagnostic value of CT features of the gallbladder in the prediction of gallstone pancreatitis. AB - PURPOSE: The aim of this retrospective study was to evaluate the diagnostic value of CT features of the gallbladder in the prediction of gallstone pancreatitis. MATERIALS AND METHODS: Eighty-six patients who underwent a diagnostic computed tomography (CT) scan for acute pancreatitis were included. The readers assessed the presence of pericholecystic increased attenuation of the liver parenchyma, enhancement of gallbladder (GB) and common bile duct (CBD) wall, pericholecystic fat strands, GB wall thickening, stone in the GB or CBD, and focal or diffuse manifestations of pancreatitis on abdominal CT scans. In addition, the maximal transverse luminal diameters of the GB and CBD were measured. RESULTS: The presence of pericholecystic increased attenuation of the liver parenchyma, GB wall enhancement and thickening, pericholecystic fat strands, stone in the GB or CBD, and diffuse manifestations of pancreatitis achieved statistical significance for differentiation of gallstone induced pancreatitis from non-biliary pancreatitis (p<0.05). The mean values of maximal transverse luminal diameter of GB and CBD were significantly higher in gallstone induced pancreatitis group (39.67+/-7.26 mm, 10.20+/-4.13 mm) than non-biliary pancreatitis group (27.01+/ 6.14 mm, 3.85+/-2.51 mm, p<0.0001). CONCLUSION: Gallbladder features of CT in patients with pancreatitis could be the valuable clues for the diagnosis of gallstone induced pancreatitis. PMID- 20576385 TI - Evolving role of 18F-FDG-PET/CT for the body tumor and metastases in pediatrics. AB - (18)F-FDG-positron emission tomography-computerized tomography ((18)F-FDG-PET/CT) scan is an important imaging tool which may provide both functional and anatomical information in a single diagnostic test. It has the potential to be a valuable tool in the noninvasive evaluation and monitoring of pediatric tumors including the metastases because (18)fluorodeoxyglucose ((18)F-FDG) is a glucose analogue that concentrates in areas of active metabolic activity. This review provides an update on functional and metabolic imaging approaches for assessment and management of the body tumor and metastases in pediatrics using a combined whole body (18)F-FDG-PET/CT scanners. We discuss the benefits include improved pediatric patients' outcome facilitated by staging and monitoring of disease and better treatment planning. It is worth to concern the preparation of children undergoing PET studies and radiation dosimetry and its implications for family and caregivers. It is important to consider the normal distribution of (18)FDG in children, common variations of the normal distribution. We show some of our cases that most tumors in children accumulate and retain FDG, allowing high-quality images of their distribution and pathophysiology either at the primary site as well as in the areas of metastatic disease. PMID- 20576386 TI - Solid non-invasive ovarian masses on MR: histopathology and a diagnostic approach. AB - PURPOSE: The purpose is to clarify the histopathology of the solid, non-invasive ovarian masses and to investigate the MR characteristics that distinguish benign from malignant. MATERIALS AND METHODS: From 1996 to 2008, we identified 38 cases with predominantly solid non-invasive ovarian masses examined by contrast MR. We evaluated the signal intensity on T2WI and degree of contrast enhancement. In 31 of these cases with dynamic contrast study, we classified the enhancing patterns of the masses into gradually increasing and plateau after rapid increase patterns. RESULT: Sixteen cases were benign sex-cord stromal tumors, three were other types of benign tumors, nine cases were diagnosed with primary malignant ovarian tumors, and 10 showed metastatic tumors. Low intensity on T2WI was observed in 15 benign and 2 malignant tumors. The gradually increasing pattern was observed in all 17 benignancies and 5 of the 14 malignancies. In the equilibrium phase, the masses were weakly enhanced in all 19 benignancies and only 4 of 19 malignancies. The diagnostic criteria, that low signal intensity masses with gradual weak enhancement are benign showed 93.3% accuracy and 100% positive predictive value. CONCLUSION: Benign solid ovarian masses tended to show low signal intensity on T2WI and gradual weak enhancement. PMID- 20576387 TI - CT and MR imaging characteristics of infantile hepatic hemangioendothelioma. AB - AIM: This study aims to analyze computed tomography (CT) and magnetic resonance (MR) imaging features of infantile hepatic hemangioendotheliomas before and after treatment. MATERIALS AND METHODS: CT and MR examinations of seven infants with biopsy proven hepatic hemangioendotheliomas were retrospectively analyzed. The distribution, number, size, imaging appearance, enhancement pattern and post treatment changes of the tumors were evaluated. RESULTS: A total of 153 hepatic hemangioendotheliomas were detected on CT (111) and MR (42) imaging. In six infants, 109/111 (98.2%) tumors were hypodense and 2/111 (1.8%) lesions contained calcification on unenhanced CT. On MR imaging, all 42 lesions in one infant were heterogeneously T1-hypointense and T2-hyperintense compared to the normal liver parenchyma. Contrast-enhanced CT and MRI showed peripheral rim (51.6%), uniform (48.4%), fibrillary (33.3%), and nodular (28.8%) contrast enhancement in the hepatic arterial phase. Homogeneous (100%), rim (98.2%) and mixed enhancement patterns were noted in tumors <1.0cm, >2.0cm and 1.0-2.0cm in diameter respectively in the hepatic arterial phase. In three patients who underwent steroid therapy, follow-up CT examination demonstrated tumor size reduction and increased intra-tumoral calcification in two patients. CONCLUSION: Infantile hepatic hemangioendotheliomas show some typical imaging features and size dependent pattern of contrast enhancement on CT and MR imaging, which allow accurate imaging diagnosis and post-treatment evaluation. PMID- 20576388 TI - Neural circuits of disgust induced by sexual stimuli in homosexual and heterosexual men: an fMRI study. AB - Few studies demonstrated neural circuits related to disgust were influenced by internal sexual orientation in male. Here we used fMRI to study the neural responses to disgust in homosexual and heterosexual men to investigate that issue. Thirty-two healthy male volunteers (sixteen homosexual and sixteen heterosexual) were scanned while viewing alternating blocks of three types of erotic film: heterosexual couples (F-M), male homosexual couples (M-M), and female homosexual couples (F-F) engaged in sexual activity. All the participants rated their level of disgust and sexual arousal as well. The F-F and M-M stimuli induced disgust in homosexual and heterosexual men, respectively. The common activations related to disgusting stimuli included: bilateral frontal gyrus and occipital gyrus, right middle temporal gyrus, left superior temporal gyrus, right cerebellum, and right thalamus. Homosexual men had greater neural responses in the left medial frontal gyrus than did heterosexual men to the sexual disgusting stimuli; in contrast, heterosexual men showed significantly greater activation than homosexual men in the left cuneus. ROI analysis showed that negative correlation were found between the magnitude of MRI signals in the left medial frontal gyrus and scores of disgust in homosexual subjects (p<0.05). This study indicated that there were regions in common as well as regions specific for each type of erotic stimuli during disgust of homosexual and heterosexual men. PMID- 20576389 TI - Dysrhythmiartifact. PMID- 20576391 TI - Case report: Emergency department diagnosis of melorheostosis in the upper extremity: a rare disease with an unusual presentation. AB - BACKGROUND: Melorheostosis is a rare disease that affects fewer than 1:1,000,000 persons worldwide and most typically affects the lower extremities. It is a non hereditary disease that may be debilitating due to chronic pain, contractures of the soft tissue, and even shortening of the affected limbs. Although it most commonly occurs in the lower extremities, melorheostosis has been reported in various locations throughout the body. OBJECTIVE: This case report describes a patient who presented to the Emergency Department (ED) with this rare disease in an uncommonly affected bone. CASE REPORT: The patient was a 21-year-old man who presented to the ED with pain in his left upper extremity that he attributed to playing sports 3 days before presentation. Plain films revealed periosteal hyperostosis typical of melorheostosis in several of his carpals, metacarpals, and phalanges, as well as the humerus and ulna. The patient was discharged with orthopedic follow-up and pain medication. CONCLUSION: Melorheostosis is a rare disease that has characteristic radiographic findings likened to the appearance of melting wax flowing down the side of a candle. In certain cases, the disease can be debilitating and may require chronic pain management and even operative intervention. If this diagnosis is made in the ED, the emergency physician should provide adequate pain management and refer the patient to an orthopedic specialist for a work-up to rule out other sclerosing bone dysplasias. PMID- 20576390 TI - Thrombolytic therapy for acute ischemic stroke beyond three hours. AB - BACKGROUND: Ischemic cerebrovascular accidents remain a leading cause of morbidity and mortality. Thrombolytic therapy for acute ischemic stroke within 3h of symptom onset of highly select patients has been advocated by some groups since 1995, but trials have yielded inconsistent outcomes. One recent trial demonstrated significant improvement when the therapeutic window was extended to 4.5h. CLINICAL QUESTION: Does the intravenous systemic administration of tPA within 4.5h to select patients with acute ischemic stroke improve functional outcomes? EVIDENCE REVIEW: All randomized controlled trials enrolling patients within 4.5h were identified, in addition to a meta-analysis of these trial data. RESULTS: The National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) clinical trials demonstrated significantly improved outcomes at 3 months, with increased rates of intracranial hemorrhage, whereas ECASS II and the Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study showed increased hemorrhagic complications without improving outcomes. Meta-analysis of trial data from all ECASS trials, NINDS, and ATLANTIS suggest that thrombolysis within 4.5h improves functional outcomes. CONCLUSION: Ischemic stroke tPA treatment within 4.5h seems to improve functional outcomes and increases symptomatic intracranial hemorrhage rates without significantly increasing mortality. PMID- 20576392 TI - Pediatric vasoocclusive crisis and weather conditions. AB - BACKGROUND: Previous studies have demonstrated associations of frequency of vasoocclusive crisis with weather conditions in adults, although relationships have been inconsistent. OBJECTIVES: Our objective was to determine if there is an association between weather conditions and pediatric emergency department (ED) visits, hospital admissions, and day and severity of pain precipitation for vasoocclusive crisis (VOC). METHODS: A retrospective observational study was performed at a large tertiary care pediatric center. We reviewed health records of all VOC patients under the age of 18 years with a chief complaint of pain and performed correlations between daily and average weekly and monthly weather conditions and frequency of painful crises. RESULTS: A total of 430 visits for VOC to the ED were documented from January 2005 to December 2006. Significant correlations were noted between the daily and weekly number of painful crises and colder temperatures (rho=-0.11, p=0.004 for daily data and r=0.25, p=0.01 weekly) and wind speed (rho=0.13, p<0.001 and r=0.25, p=0.01). The monthly number of painful crises was moderately correlated with temperatures (r=-0.42, p=0.04). The average monthly pain score was higher in more humid months (r=0.44, p=0.03). CONCLUSION: We found significant correlations of VOC with weather conditions where colder temperatures and higher wind speed were associated with a higher incidence of VOC in children. Health care providers as well as parents should be aware of these findings and ensure that preventive measures are instituted in patients at risk. PMID- 20576393 TI - Laparoscopic transposition of the left renal vein into the inferior vena cava for nutcracker syndrome. AB - Reimplantation of the left renal vein into the infrarenal inferior vena cava is the standard surgical procedure for nutcracker syndrome. A 40-year-old woman with a solitary left kidney suffered from left lumbar pain and hematuria. Imaging techniques found a large kidney with nutcracker syndrome. A totally laparoscopic transposition of the left renal vein was performed. Twelve months later, the patient is improved and has no more hematuria. Duplex scan showed no residual stenosis. Laparoscopic transposition of the left renal vein into the inferior vena cava is feasible with short length of stay and good short-term result. PMID- 20576394 TI - Impact of obesity on venous hemodynamics of the lower limbs. AB - BACKGROUND: Obesity is a risk factor for chronic venous insufficiency and venous thromboembolism. The aim of this study was to compare venous flow parameters of the lower limbs assessed by duplex ultrasound scanning in obese and nonobese individuals according to body mass index (BMI). METHODS: Venous hemodynamics were studied in a prospective cohort study in nonobese (BMI <25 kg/m(2)) and obese individuals (BMI >30 kg/m(2)). Diameter, flow volume, peak, mean, and minimum velocities were assessed. RESULTS: The study examined 36 limbs in 23 nonobese individuals and 44 limbs in 22 obese individuals. The diameter of the femoral vein was significantly greater in obese (8.5 +/- 2.2 mm) vs nonobese (7.1 +/- 1.6 mm; P = .0009) limbs. Venous peak and minimum velocities differed between nonobese and obese individuals (14.8 +/- 7.2 vs 10.8 +/- 4.8 cm/s [P = .0071] and 4.0 +/- 3.6 vs 1.7 +/- 6.3 cm/s [P = .056]). Calculation of venous amplitude and shear stress showed significantly higher values in nonobese vs obese (18.8 +/- 9.4 vs 12.5 +/- 9.3 cm/s [P = .003] and 2.13 +/- 2.2 dyn/cm(2) vs 1.6 +/- 2.7 dyn/cm(2) [P = .03]). Spearman rank correlation revealed a significant inverse correlation between waist-to-hip ratios and waist circumference and venous peak velocity, mean velocity, velocities amplitude (peak velocity-minimum velocity), and shear stress. CONCLUSION: Lower limb venous flow parameters differ significantly between healthy obese and nonobese individuals. These findings support the mechanical role of abdominal adipose tissue potentially leading to elevated risk for both venous thromboembolism and chronic venous insufficiency. PMID- 20576395 TI - Deglutition syncope: a manifestation of vagal hyperactivity following carotid endarterectomy. AB - A 61-year-old man with left amaurosis fugax and bilateral >80% internal carotid artery stenoses underwent a left carotid endarterectomy. On the first postoperative day, he developed hypotension, bradycardia, and chest pain with food ingestion. He was diagnosed as having deglutition syncope and was treated with oral anticholinergics. Similar symptoms occurred when he underwent a right carotid endarterectomy. Deglutition syncope is a neurally mediated situational syncope resulting from vagus nerve over-activity. This is the first report of deglutition syncope associated with carotid endarterectomy. It is important to recognize and differentiate these symptoms from other causes of postendarterectomy hemodynamic instability. PMID- 20576396 TI - Upper extremity ischemia treated with tissue repair cells from adult bone marrow. AB - BACKGROUND: Unreconstructable critical ischemia with gangrene of the upper extremity is rarely due to atherosclerosis alone, and few treatment options exist. We describe a patient with gangrene of both hands as a result of unreconstructable atherosclerotic disease of both upper extremities who was successfully treated with tissue repair cells (TRCs) produced from the patient's bone marrow. METHODS: A patient with type 1 diabetes was referred with bilateral upper extremity digital gangrene due to unreconstructable forearm and hand atherosclerosis. He was evaluated for therapeutic angiogenesis using TRCs. RESULTS: Following the intramuscular injection of TRCs produced from autologous bone marrow stem cells, the patient demonstrated improved arterial perfusion and a durable clinical response with healing of all amputation sites and cessation of pain. CONCLUSIONS: The production of TRCs results in the expansion of stem and early progenitor cells, including CD90+ mesenchymal cells and endothelial progenitor cells. This is the first reported case of end-stage upper extremity ischemia treated with TRCs harvested from adult bone marrow. PMID- 20576397 TI - Younger women with symptomatic peripheral arterial disease are at increased risk of depressive symptoms. AB - OBJECTIVES: Gender disparities, particularly among young women with cardiovascular disease, are a growing cause for concern. Depression is a prevalent and prognostically important comorbidity in peripheral arterial disease (PAD), but its prevalence has not been described as a function of gender and age. Therefore, we compared depressive symptoms at the time of PAD diagnosis and 6 months later by gender and age in PAD patients. METHODS: The study enrolled 444 newly diagnosed patients with PAD (32% women) from two Dutch vascular outpatient clinics. Patients' depressive symptoms were assessed with the 10-item Center for Epidemiological Studies Depression Scale (CES-D) at baseline and 6 months later (CES-D scores >or=4 indicate significant depressive symptoms). Logistic regression models were constructed to evaluate the relationship among four gender age groups (women <65 and >or=65 years; men <65 and >or=65 years [reference category]) and baseline and 6-month follow-up depressive symptoms. RESULTS: Initially, 33% of women <65 years had significant depressive symptoms, and 6 months later, significant depressive symptoms had developed in 19% of the other younger women. These rates were much higher than other gender-age groups (range at baseline, 11%-16%; 6-month incidence, 6%-10%; P or=65 years, whereas other gender-age groups were not at risk. Additional adjustment for change in the ankle-brachial index did not explain the increased depression risk in younger women (OR, 3.5; 95% CI, 1.2-10.2). CONCLUSIONS: Significant depressive symptoms are more common in younger women with PAD than in other gender-age groups, both at the time of diagnosis and 6 months later. To eradicate gender-based disparities in PAD, depression screening and monitoring in younger women may be an important direction for future research and intervention. PMID- 20576398 TI - CAPTURE 2 risk-adjusted stroke outcome benchmarks for carotid artery stenting with distal embolic protection. AB - OBJECTIVE: Many medical procedures undergo rapid evolution and process of care improvements after introduction. National outcome standards are useful to help physicians, institutions, and other stakeholders evaluate the quality of their programs and take action when suboptimal outcomes are identified. The purpose of this analysis was to derive contemporary risk-adjusted stroke rates from a large, contemporary, independently assessed outcome database within 30 days after carotid artery stenting (CAS) in the United States. METHODS: The second phase of carotid ACCULINK/ACCUNET post approval trial to uncover rare events (CAPTURE 2) is an ongoing prospective, multicenter, clinical trial conducted to assess CAS outcomes in the general practice setting after device approval for high surgical risk patients (symptomatic with >50% stenosis or asymptomatic with >80% stenosis). A neurologist examined the patients before the procedure, at 1 day and 30 days after CAS. The primary endpoint was a composite of death, any stroke, or myocardial infarction (MI) within the periprocedural period. Strokes and neurologic events suspected to be strokes were adjudicated by an independent clinical events adjudication committee. Logistic regression analysis including stepwise logistic and multivariable modeling was performed to determine clinical predictors of periprocedural stroke outcome and generate a parsimonious model that could be used for a clinical standard. RESULTS: Five thousand two hundred ninety-seven consecutive patients (5297) had CAS performed by 459 physicians at 186 sites before the data cutoff of January 10, 2009. The 30-day rate of stroke was 2.7% (95% confidence interval [CI], 2.3-3.2). Multivariable predictors of periprocedural stroke included age, symptomatic status, and dwell time of embolic protection device. A parsimonious model P(i) = 1/(1+e (-(-3.83 + 0.51 x (symptomatic) + 0.31 x (age >or=80) + 0.62 x (age >or=80 x symptomatic))), including symptomatic and octogenarian status and the term of the interaction of the two, was established based on consideration of clinical predictors, clinical interaction, and practicability. CONCLUSION: CAS outcomes in patients at high surgical risk have comparable periprocedural outcomes to published randomized trials of endarterectomy for patients at standard surgical risk. A model is presented for calculating a contemporary national standard for risk-adjusted stroke rates. Quality improvement measures could be based on relative performance to this benchmark and could improve overall outcomes for patients undergoing CAS. PMID- 20576399 TI - The Quality of Cancer Care initiative in the Netherlands. AB - BACKGROUND: In 2007 the Dutch Cancer Society formed a 'Quality of Cancer Care' taskforce comprising medical specialists, from all disciplines involved in the care for cancer patients. This taskforce was charged with the evaluation of quality of cancer care in the Netherlands and the development of strategies for improvement. OBJECTIVE: The experts first focused on the relation between procedural volume and patient outcome and later aimed to identify other factors associated with high and low quality of the care provided in different regions and (types of) hospitals in the Netherlands. The question if cancer care in the Netherlands could be organized differently to assure high quality of care for all patients, was the main subject of investigation. METHODS: An extensive review of the literature on infrastructure, volume and specialization on the one hand and outcome on the other was performed. In addition, a meta-analysis of the volume outcome relationship for pancreatectomies, bladder, lung, colorectal and breast cancer resections was performed. Finally, variation in quality of cancer care between regions, groups of hospitals and individual hospitals in our country was investigated on data from the Netherlands Cancer Registry. RESULTS: In the Netherlands quality of care varies by hospital and region. These differences are not limited to surgical procedures and postoperative mortality, but are also demonstrated in other parts of the care process. Differences are only partly explained by differences in infrastructure, procedural volume and specialization between hospitals. Essential information on differences in case mix between these hospitals are lacking from the Netherlands Cancer Registry. More detailed clinical data are needed to reveal the mechanisms behind the differences in quality of care between Dutch hospitals. CONCLUSION: On a population level, there is potential for improvement of outcome for cancer patients in the Netherlands by reducing variation in optimal treatment rates between hospitals. Not only treatment of tumours with a low incidence but also other complex or high risk cancer procedures should be provided in a specialized setting, with the right infrastructure, sufficient volume and adequate expertise. In addition, outcomes should be monitored continuously and fed back to individual caregivers. PMID- 20576400 TI - Reproducibility of peripheral quantitative computed tomography measurements at the radius and tibia in healthy pre- and postmenopausal women. AB - PURPOSE: The objectives of this study were to utilise the XCT-2000 pQCT scanner to determine the mean values and the reproducibility of in vivo total, trabecular, and cortical volumetric bone measurements at distal and diaphyseal sites of the radius and the tibia, as well as calf muscle and subcutaneous fat areas, in healthy pre- and postmenopausal women. METHODS: Twenty-nine women (14 premenopausal and 15 postmenopausal) were recruited to participate in this study. Distal and diaphyseal sites of the radius (at 4% and 20% of the length of the radius) and tibia (at 4%, 38%, and 66% of the length of the tibia) were examined. RESULTS: The root mean square coefficient of variation for measurements at the distal tibia gave the most favorable reproducibility values for total (1.5%) and trabecular (1.6%) density, whereas the diaphyseal tibia showed the most favorable reproducibility value for cortical density (0.3%). The root mean square coefficients of variation for measurements of muscle and fat cross-sectional areas at the calf were 0.6% and 0.7%, respectively. At the distal tibia, the mean values for total (P < .05) and trabecular (P < .01) density were significantly lower in postmenopausal women than in premenopausal women. CONCLUSIONS: The data presented here indicate that XCT-2000 pQCT scans at the tibia provide highly reproducible measurements of total, cortical, and trabecular bone as well as muscle and fat cross-sectional areas. Furthermore, significant differences in volumetric bone measurements between healthy pre- and postmenopausal women were evident only at the distal tibia, suggesting that this site warrants further study. PMID- 20576401 TI - Improved antibiotic impregnated cement prosthesis for treating deep hip infection: a novel design using hip compression screw. AB - A 2-stage revision arthroplasty has been suggested as the optimal treatment for deep infections in the hip joint. Improvement of the surgical technique to increase the interim function is subject to investigation. From 2004 to 2007, we collected a cohort of 15 consecutive patients who were treated by a novel design augmented with a modified hip compression screw. No fracture of the cement spacer occurred. We believe the modified hip compression screw is a good alternative for the functional endoskeleton of an antibiotic loaded cement prosthesis in the treatment of deep hip infection. PMID- 20576402 TI - Introduction to the special issue on biomedical image technologies and methods. PMID- 20576403 TI - Static and dynamic periosteal elevation: a pilot study in a pig model. AB - The osteoinductive potential of periosteum and bone can be stimulated by elevating the periosteum in a distraction-like modus, but also by an ad-hoc elevation. This was tested and proved in an experiment in 9 Goettingen mini-pigs with elevation heights of 5, 10 and 15mm. Specially designed and perforated titanium meshes were implanted subperiosteally to compare the dynamic elevation procedure with static shielding. The cumulative results for bone formation underneath the mesh were 66% in dynamic and 67% in non-dynamic elevation. The cumulative results for mineralization of the bone regenerates in comparison with the underlying basal bone of the skull showed independently from the technique applied no difference bigger than 5%. No major difference in bone formation could be observed in this pilot study. The main advantages of dynamic periosteal elevation and static shielding are minimal invasion and morbidity. Periosteal elevation could be applied in cranio-maxillofacial surgery, in preimplantological augmentation and in reconstructive surgery of the skull; applications in other specialties may be possible. PMID- 20576404 TI - Chemokines and cutaneous lymphoma. AB - Chemokines are small molecules of 8-10kDa that induce chemotaxis and activation of certain subsets of leukocytes. It has been recently shown that chemokines have broader function such as inhibition of apoptosis of target cells. The expression patterns of chemokines and chemokine receptors are specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ specific human diseases. Primary cutaneous lymphomas are characterized by proliferation of clonally expanded lymphocytes in skin, but without detectable systemic involvement at the first diagnosis. Many chemokines are reported to be expressed in lesional skin of cutaneous lymphoma. Moreover, tumor cells of a certain group of cutaneous lymphoma express limited numbers of chemokine receptors, suggesting that interactions between chemokines and their receptors may explain skin-tropism of these types of lymphoma. This article focuses on chemokines expressed in lesional skin of cutaneous lymphoma and discusses their possible roles in disease progression. PMID- 20576405 TI - Protein adsorption under electrical stimulation of neural probe coated with polyaniline. AB - Polyaniline (PANI) nanoparticles were successfully polymerized on the surface of Pt electrode to form nanostructured films. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) micrographs showed that the just-synthesized films were compact with diameter of nanoparticles on films about 50 and 30nm for HClO(4) and citric acid doped PANI films, respectively. And the surface of the electrode was coated completely with PANI films. After electrical stimulation for 1 month in 0.9% sodium chloride solution, there were no fissures appearing on PANI films. The compact film would act as a protecting membrane of the Pt surface, and is suitable to be used as the electrode coating for long-time performance. The time frame of human plasma fibronectin (FN) and bovine serum albumin (BSA) adsorption illustrated that electrical stimulation enhanced the amount of protein adsorption on PANI films up to 1.7-fold increase as compared to that without electrical stimulation. The SEM images of BSA adsorption for 120min indicated that electrical stimulation might initiate the aggregation of BSA, and the nanostructure of the PANI films could inhibit the aggregation. We also found that the protein adsorption decreased conductivity of PANI films, which maybe due to the protein barriers formed on them. These results provided a good reference for the use of conducting polymers as neural probe coating. PMID- 20576406 TI - Delivery of brachytherapy for cervical cancer: organisational and technical advice to facilitate high-quality care. AB - AIMS: Brachytherapy is a standard therapy for cervical cancer; it allows for the delivery of a high dose of radiation to the tumour while sparing the surrounding healthy tissues. With this document, the Brachytherapy Cervical Cancer Expert Working Group (BCCEWG) aimed to provide advice on organisational and technical aspects of the delivery of brachytherapy services in Ontario, Canada. MATERIALS AND METHODS: We sought technical documents, practice guidelines and standards through an environmental scan of internet resources, an iterative search of the literature on MEDLINE and EMBASE, and a search of reference lists of included documents. RESULTS: We identified 20 guidance documents authored by 10 organisations; 11 documents were identified through the environmental scan, five through the literature search and four from reference lists. The recommendations included in this document were developed by the BCCEWG through the selection and review of the evidence and informal consensus. CONCLUSIONS: These organisational recommendations aim to set the stage for high-quality delivery of brachytherapy for cervical cancer services in the province of Ontario, Canada. They address the characteristics of the practice setting, including facilities, equipment, delivery suite, imaging technologies, treatment planning and dosimetry; the practice team, including team members, roles, training, team caseload/volumes and qualifications; and the quality assurance domain, including documentation, audit, safety and quality control. PMID- 20576407 TI - The revised American Thyroid Association management guidelines 2009 for patients with differentiated thyroid cancer: an evidence-based risk-adapted approach. PMID- 20576408 TI - Improving survival with thoracic radiotherapy in patients with small cell lung cancer. The CONVERT and the REST Trials. PMID- 20576409 TI - Toxicological evaluation of smokeless tobacco: 90-day rodent feeding studies. AB - This manuscript presents data from 90-day toxicology studies designed to characterize the subchronic effects of a smokeless tobacco blend and an aqueous extract of that blend when administered to rodents in NTP-2000 feed. Positive control (nicotine tartrate) and treatment groups were matched for a range of nicotine levels. The doses evaluated were 0.3, 3, and 6 mg nicotine/kg body weight/day in Wistar Hannover rats and 6, 60, and 120 mg nicotine/kg/day in CD-1 mice. Variables evaluated included plasma nicotine and cotinine, body weights, feed consumption, clinical observations, clinical and anatomic pathology (including organ weights), and histopathology. Plasma nicotine and cotinine levels were dose-responsive. Key effects such as body weight reductions and organ weight changes occurred in rats and mice predominantly at the highest doses of test articles and positive control in the absence of treatment-related gross or histopathological changes. Organ weight changes were attributed mainly to the lower body weights of treated vs. control groups. The blend- and extract-induced effects generally paralleled each other and the nicotine-induced effects. Based on these studies, the doses evaluated spanned the no observable adverse effect level, the lowest observable adverse effect level and the maximum tolerated dose. PMID- 20576410 TI - Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition. AB - The activity of Uncaria tomentosa preparations on cancer cells was studied using in vitro and in vivo models. IC (50) values were calculated for preparations with different quantitative and qualitative oxindole alkaloid composition: B/W(37) - bark extracted in water at 37 degrees C, B/W(b)--bark extracted in boiling water, B/50E(37) --bark extracted in 50% ethanol at 37 degrees C, B/E(b)--bark extracted in boiling 96% ethanol, B/96E(37) --bark extracted in 96% ethanol at 37 degrees C and B/SRT--bark extracted in water and dichloromethane. Generally, the results obtained showed a high correlation between the total oxindole alkaloid content (from 0.43% to 50.40% d.m.) and the antiproliferative activity of the preparations (IC(50) from >1000 MUg/ml to 23.57 MUg/ml). B/96E(37) and B/SRT were the most cytotoxic preparations, whereas the lowest toxicity was observed for B/W(37). B/96E(37) were shown to be active against Lewis lung carcinoma (LL/2) [IC(50) =25.06 MUg/ml], cervical carcinoma (KB) [IC(50) =35.69 MUg/ml] and colon adenocarcinoma (SW707) [IC(50) =49.06 MUg/ml]. B/SRT was especially effective in inhibiting proliferation of cervical carcinoma (KB) [IC(50) =23.57 MUg/ml], breast carcinoma (MCF-7) [IC(50) =29.86 MUg/ml] and lung carcinoma (A-549) [IC(50) =40.03 MUg/ml]. Further animal studies on mice bearing Lewis lung carcinoma showed significant inhibition of tumor growth by B/W(37) administered for 21 days at daily doses of 5 and 0.5 mg (p=0.0009). There were no significant changes in the cell cycles of tumor cells with the exception of cell decrease at the G2/M phase after the administration of B/96E(37) at a daily dose of 0.5 mg and the G(1)/G(0) cells cycle arrest demonstrated after the B/SRT therapy at a daily-dose of 0.05 mg. All tested preparations were non-toxic and well tolerated. PMID- 20576411 TI - Effect of combined administration of ginger (Zingiber officinale Roscoe) and atorvastatin on the liver of rats. AB - Ginger is known to possess hypolipidemic, antioxidant and hepatoprotective properties. Combination therapy often takes advantage of complementary effects of different agents. This study investigated the combined effect of ginger extract (GE) and atorvastatin on lipid profile and on atorvastatin-induced hepatic injury. Rats were randomized into: control; GE (400 mg/kg); atorvastatin (20 mg/kg) alone or with GE or vitamin E, and atorvastatin (80 mg/kg) alone or with GE or vitamin E. Administration of 80 mg/kg atorvastatin for 4 weeks had major hepatotoxic effect whereas the lower dose (20 mg/kg) seems to cause mild liver injury. Besides lowering serum total cholesterol and hepatic superoxide dismutase (SOD) and catalase (CAT), atorvastatin significantly increased serum aminotransferases, hepatic malondialdehyde (MDA) and nitric oxide (NO). Concurrent administration of GE and atorvastatin had the opposite effect. Histopathological study revealed that GE reduced liver lesions induced by atorvastatin. The results indicate that the ability of ginger to lower serum cholesterol and to decrease aminotransferases, MDA and NO is clinically important, because its chronic administration will neither lead to side-effects nor to hepatic changes as occurs with high atorvastatin doses. Therefore, combination regimens containing GE and low dose of statins could be advantageous in treating hypercholesterolemic patients which are susceptible to liver function abnormalities. PMID- 20576412 TI - Chemical composition of the SFE-CO extracts from Cajanus cajan (L.) Huth and their antimicrobial activity in vitro and in vivo. AB - The in vitro and in vivo antimicrobial activities of SFE-CO2(supercritical fluid extraction) extracts and ethanol extracts from Cajanus cajan (L.) Huth were investigated. The flavonoid compounds orientin, vitexin, isovitexin, pinostrobin and the stilbene cajaninstilbene acid were detected in SFE-CO2 extracts by HPLC DAD. In vitro antimicrobial activities of the extracts were evaluated against eight microbial strains (the bacteria Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Pseudomonas aeruginosa, Escherichia coli; and the fungi Aspergillus niger and Candida albicans). A marked inhibitory effect of the SFE extracts was observed against Staphylococcus epidermidis, Staphylococcus aureus and Bacillus subtilis. The IC(50) of SFE-CO2 extracts ranged from 0.0557 mg/ml to 0.0689 mg/ml consisting of cancer (MCF-7 (0.0557 mg/ml)) as well as non-cancer (BHK-21 (0.0641 mg/ml), RAW264.7 (0.0689 mg/ml) and Vero (0.0625 mg/ml)) cells. Flow cytometry (FCM) was used to analyze death rate of the most sensitive strain (Staphylococcus aureus) caused by the SFE extracts. Additionally, the whole cell proteins of Staphylococcus aureus were analyzed by SDS-PAGE to detect if there were changes in protein patterns. In vivo antimicrobial activity was studies in mice that had been inoculated with Staphylococcus aureus. The potential mechanism of antimicrobial activity in vivo was studied by histopathology. PMID- 20576413 TI - Antidiabetic effect of S-allylcysteine: Effect on plasma and tissue glycoproteins in experimental diabetes. AB - The present study was conducted to investigate the effect of S-allylcysteine (SAC) on dearrangement in glycoprotein levels in the streptozotocin induced diabetic model. SAC (150 mg/kg b.w./day) was administered orally for 45 days to normal and diabetic rats. STZ-induced diabetic rats showed significant increase in blood glucose and glycoprotein components such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidneys of diabetic rats. Oral administration of SAC to diabetic rats for a period of 45 days normalized all the above-mentioned biochemical parameters. The antihyperglycemic effect of SAC was compared with glyclazide, a well-known antihyperglycemic drug. The present study indicates that SAC possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect. PMID- 20576414 TI - Anthelmintic activity of steroidal saponins from Paris polyphylla. AB - The present study was undertaken to investigate the anthelmintic activity of crude extracts and pure compounds from the rhizomes of Paris polyphylla. The methanol extract showed a promising anthelmintic activity against Dactylogyrus intermedius (EC(50) value=18.06 mg l(-1). Based on these finding, the methanol extract was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording two known steroidal saponins showing potent activity, dioscin and polyphyllin D. Both dioscin and polyphyllin D exhibited significant activity against D. intermedius with EC(50) values of 0.44 and 0.70 mg l(-1), respectively, which were more effective than the positive control, mebendazole (EC(50) value=1.25 mg l(-1)). The acute toxicities (LC(50)) of dioscin and polyphyllin D for goldfish were 1.37 and 1.08 mg l(-1), respectively. These results indicated that P. polyphylla extract and the isolated compounds are potential natural agents for the control of Dactylogyrus infestation. This is the first report on in vivo anthelmintic investigation for P. polyphylla. PMID- 20576415 TI - S-allylcysteine reduces the MPTP-induced striatal cell damage via inhibition of pro-inflammatory cytokine tumor necrosis factor-alpha and inducible nitric oxide synthase expressions in mice. AB - We have recently demonstrated that S-allylcysteine (SAC) induces protection on neurochemical, biochemical and behavioral markers of striatal damage in different neurotoxic animal models - including a murine model induced by 1-methyl-4-phenyl 1,2,3,6-tetrahydropiridinium (MPTP) injection to mice - indicating that pro oxidant reactions underlie neurotoxicity in these models (Garcia et al. 2008). In this work we investigated whether SAC can protect the striatum of mice from the morphological alterations in the MPTP toxic model, and if this response is correlated with a reduction in pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expressions, and further reduction in astrocyte activation (glial fibrillary acidic protein (GFAP) expression). The striatal tissue from MPTP injected animals (30 mg/kg, i.p., *5 days) showed a significant degree of cell damage and enhanced immunoreactivities to GFAP, TNF-alpha and iNOS, as well as an enhanced number of apoptotic nuclei. Treatment of mice with SAC (120 mg/kg, i.p., *5 days) in parallel to MPTP significantly reduced or prevented all these markers. Our results suggest that MPTP-induced morphological alterations recruit a pro-inflammatory component triggered by cytokine TNF-alpha release and nitric oxide formation, which is sensitive to the antioxidant properties of SAC. This antioxidant is an effective experimental tool to reduce the brain lesions associated with oxidative damage and inflammatory responses. PMID- 20576416 TI - Isolation of adenosine, iso-sinensetin and dimethylguanosine with antioxidant and HIV-1 protease inhibiting activities from fruiting bodies of Cordyceps militaris. AB - According to previous studies, a close relationship between oxidative stress and AIDS suggests that antioxidants might play an important role in the treatment of AIDS. Cordyceps militaris was selected from nine edible mushrooms by assay of inhibition of erythrocyte hemolysis. Macroporous adsorption resin and HPLC were used to purify three micromolecular compounds named L3a, L3b and L3c. L3a was identified to be adenosine with the molecular formula C(10)H(13)N(5)O(4); L3b was 6,7,2',4',5'-pentamethoxyflavone with the molecular formula C(20)H(20)O(7), and L3c was dimethylguanosine with the molecular formula C(12)H(17)N(5)O(5). The compound 6,7,2',4',5'-pentamethoxyflavone was first isolated from C. militaris. The assay of inhibition of HIV-1 protease (HIV-1 PR) was based on the fact that the expression of this enzyme can inhibit the growth of E. coli. This is a new screening system for HIV-1 PR inhibitors. Both L3a and L3b showed high inhibition to HIV-1 PR. These compounds could be new anti-HIV-1 PR drugs. PMID- 20576417 TI - Predictive accuracy of the pneumonia severity index vs CRB-65 for time to clinical stability: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. AB - BACKGROUND: The Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better. METHODS: A secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated. RESULTS: The area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of -0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001-0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02-0.082) were both statistically significant. CONCLUSIONS: This study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome. PMID- 20576418 TI - Respiratory muscle strength in pregnancy. AB - BACKGROUND: Muscle respiratory strength studies during pregnancy are very scarce. The aim of this paper is to describe maximum inspiratory (PImax) and expiratory (PEmax) mean pressure values in women during their first pregnancy and to determine the relationship between the anthropometric, morphologic and physiologic variables of these pressures. METHODS: One hundred and twenty women (120) primigravidas were studied from the 5th to 40th gestational week, ages ranging from 20 to 29 years old, euthrophic and with low risk pregnancies. RESULTS: PImax and PEmax mean values were 88.5 +/- 16.52 cmH(2)O and 99.76 +/- 18.19 cmH(2)O respectively. There was no association between gestational age and PImax (r = -0.06; p = 0.49) or PEmax (r = -0.11; p = 0.22). There was also no difference between PImax and PEmax during pregnancy trimesters and no correlation between pregnancy age and the pressures in each trimester. Height was the only anthropometric variable indicating a significant PImax (r = 0.20; p = 0.02) association. Fundal uterus height and inter-recti abdominis distance were not associated to respiratory pressure values. PEmax is not associated with the group of predictor variables (p = 0.127) and PImax demonstrated an independent association with height and dyspnea during physical exertion reflected by the following equation: PImax = 0.6 + 57.9 height - 1.68 dyspnea under effort. The present study suggests that inspiratory and expiratory maximum pressure values are not altered during different stages of pregnancy, however longitudinal studies are needed to assess changes over time. PMID- 20576419 TI - Beneficial effect of inhaled mannitol and cough in asthmatics with mucociliary dysfunction. AB - Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance (MCC) leading to mucus plugs, and airway obstruction. Inhaled mannitol improves mucus clearance in other hypersecretory diseases. This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction. Seven stable asthmatics, age 52 +/- 20 yr, lifelong non smokers, without the diagnosis of bronchiectasis, with chronic cough and sputum production, treated with inhaled corticosteroids participated in the study. MCC and cough clearance (CC) was measured on 4 visits: at baseline (no cough or mannitol), with mannitol (240 and 480 mg) and cough control (no mannitol) over total 90 min using a radioaerosol technique and imaging with a gamma camera. Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min. Premedication with eformoterol (12 MUg) on all visits protected all subjects from bronchoconstriction (fall in FEV(1) > 15%) in response to mannitol. Mean (+/-SD) clearance over 60 min increased from 5.5 +/- 5.6% at baseline and 7.3 +/- 6.6% with cough control to 19.5 +/- 14.6% and 26.4 +/- 11.5% with 240 mg (p < 0.003) and 480 mg (p < 0.0001) of mannitol respectively. Total clearance (MCC + CC) over 90 min increased from 6.9 +/- 6.5% (baseline) and 12.6 +/- 8.3% without mannitol (cough control) to 34.6 +/- 13.5 and 36.6 +/- 10.4% with 240 and 480 mg mannitol respectively (p < 0.0001). Clearance over 90 min at baseline was not significantly different to cough control (p > 0.05). Mannitol improved clearance in all lung regions (p < 0.005). In conclusion, mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance. Clinical Trial registered with www.anzctr.org.au; Number ACTRN 12609001066279.aspx. PMID- 20576420 TI - Inhibition of IgE production by docosahexaenoic acid is mediated by direct interference with STAT6 and NFkappaB pathway in human B cells. AB - Nutrition can modify the onset or severity of diseases and recent changes in eating habits are supposed to promote immunoglobulin (Ig) E-dependent disorders. The n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) possesses immunomodulatory properties and has been shown to influence chronic and allergic inflammatory disorders in vivo. Here, we examined the impact of DHA on primary human B cells to elucidate its potential role in direct regulation of IgE production and the underlying mechanisms of action. Therefore, cells were stimulated with anti-CD40/interleukin (IL)-4 in the presence of DHA. Subsequently, Ig production, generation of antibody secreting cells, epsilon germline transcript (EGLT) and activation induced desaminase (AID) expression as well as IgE relevant signaling pathways were analyzed. Our results reveal that DHA inhibits IgE production (75+/-14%) and, depending on concentration, the differentiation of IgE secreting cells (59+/-27%). The reduction of IgE is accompanied by a direct inhibition of the switching process indicated by decreased EGLT and AID transcription. DHA causes both a reduced CD40 dependent nuclear factor kappaB-p50 translocation into the nucleus and a decreased IL-4 receptor expression which was associated with a reduction of IL-4 driven signal transducer and activator of transcription 6 phosphorylation. Taken together, DHA inhibits IgE production of human B cells by direct interference with both the CD40 and the IL-4 signaling pathway. The data provide one explanation for the anti-allergic role of DHA at the molecular level. PMID- 20576421 TI - Serum palmitic acid-oleic acid ratio and the risk of coronary artery disease: a case-control study. AB - Serum free fatty acids are risk factors for future coronary artery disease (CAD). We investigated the association between serum palmitic acid (PA)-oleic acid (OA) ratio and CAD risk in a case-control (n=108/129) study. The PA-OA ratio was associated with future CAD events independently of standard lipid values. The PA OA ratio was significantly associated with the risk of fatal CAD [odds ratio (OR): 60.4; 95% confidence interval (CI): 11.5-316.9; P<.001] while inversely associated in nonfatal CAD group (OR: 0.11; 95% CI: 0.02-0.53; P<.01), and no distinct modification by sex was found. Receiver-operating characteristic (ROC) analysis found that PA-OA ratio did as well as triglyceride (TG) and apolipoprotein B (apo B)-high-density lipoprotein cholesterol (HDLC) ratio at discriminating fatal CAD (area under ROC, TG, 0.692; apo B-HDLC, 0.683; PA-OA, 0.768, P<.001), and had similar effect with HDLC at discriminating nonfatal CADs (area under ROC, HDLC, 0.649; PA-OA, 0.659, P<.01).These findings suggested that PA-OA ratio did as well as and even better than traditional risk factors and arteriography examination in discriminating fatal and nonfatal CAD events. Serum PA-OA ratio could be a new factor for CAD risk assessment and prediction. PMID- 20576422 TI - Dietary isoflavone increases insulin-like growth factor-I production, thereby promoting hair growth in mice. AB - Sensory neurons release calcitonin gene-related peptide (CGRP) upon activation. We previously demonstrated that CGRP increases insulin-like growth factor-I (IGF I) production in various tissues of mice including the skin. We demonstrated that isoflavone increases the CGRP synthesis in the dorsal root ganglion (DRG) neurons in rats. Since IGF-I plays a critical role in hair growth, we hypothesized that isoflavones may promote hair growth by increasing the IGF-I production in hair follicles. We examined this hypothesis using wild-type (WT) and CGRP-knockout (CGRP(-/-)) mice. Isoflavone significantly increased the CGRP mRNA levels in DRG neurons isolated from WT mice (P<.01). Administration of isoflavone for 3 weeks increased the dermal levels of CGRP, IGF-I and IGF-I mRNA in WT mice, but not in CGRP(-/-) mice. Isoflavone administration increased the immunohistochemical expression of IGF-I in hair follicle dermal papilla cells in WT mice. Significant enhancements of hair follicle morphogenesis, hair regrowth, and hair pigmentation were also observed in WT mice administered isoflavone. However, none of these effects in WT mice were observed in CGRP(-/-) mice. These observations strongly suggest that isoflavone might increase IGF-I production in the hair follicle dermal papilla cells in mice through increasing CGRP production in the sensory neurons, thereby promoting hair growth associated with melanogenesis in mice. PMID- 20576423 TI - Separation of packaging plastics by froth flotation in a continuous pilot plant. AB - The objective of the research was to apply froth flotation to separate post consumer PET (Polyethylene Terephthalate) from other packaging plastics with similar density, in a continuously operated pilot plant. A representative sample composed of 85% PET, 2.5% PVC (Polyvinyl Chloride) and 11.9% PS (Polystyrene) was subjected to a combination of alkaline treatment and surfactant adsorption followed by froth flotation. A mineral processing pilot plant, owned by a Portuguese mining company, was adapted for this purpose. The experimentation showed that it is possible to produce an almost pure concentrate of PET, containing 83% of the PET in feed, in a single bank of mechanical flotation cells. The concentrate grade attained was 97.2% PET, 1.1% PVC and 1.1% PS. By simulation it was shown that the Portuguese recycling industry specifications can be attained if one cleaning and one scavenger stages are added to the circuit. PMID- 20576424 TI - A strategy for development of electrochemical DNA biosensor based on site specific DNA cleavage of restriction endonuclease. AB - A new strategy for development of electrochemical DNA biosensor based on site specific DNA cleavage of restriction endonuclease and using quantum dots as reporter was reported in this paper. The biosensor was fabricated by immobilizing a capture hairpin probe, thiolated single strand DNA labeled with biotin group, on a gold electrode. BfuCI nuclease, which is able to specifically cleave only double strand DNA but not single strand DNA, was used to reduce background current and improve the sensitivity. We demonstrated that the capture hairpin probe can be cleaved by BfuCI nuclease in the absence of target DNA, but cannot be cleaved in the presence of target DNA. The difference before and after enzymatic cleavage was then monitored by electrochemical method after the quantum dots were dissolved from the hybrids. Our results suggested that the usage of BfuCI nuclease obviously improved the sensitivity and selectivity of the biosensor. We successfully applied this method to the sequence-selective discrimination between perfectly matched and mismatched target DNA including a single-base mismatched target DNA, and detected as low as 3.3 * 10(-14) M of complementary target DNA. Furthermore, our above strategy was also verified with fluorescent method by designing a fluorescent molecular beacon (MB), which combined the capture hairpin probe and a pair of fluorophore (TAMRA) and quencher (DABCYL). The fluorescent results are consistent with that of electroanalysis, further indicating that the proposed new strategy indeed works as we expected. PMID- 20576425 TI - Engineering bacteria to recognize and follow small molecules. AB - The ability to recognize and react to specific environmental cues allows bacteria to localize to environments favorable to their survival and growth. Synthetic biologists have begun to exploit the chemosensory pathways that control cell motility to reprogram how bacteria move in response to novel signals. Reprograming is often accomplished by designing novel protein or RNA parts that respond to specific small molecules not normally recognized by the natural chemosensory pathways. Additionally, cell motility and localization can be coupled to bacterial quorum sensing, potentially allowing consortia of cells to perform complex tasks. PMID- 20576426 TI - Treatment of a BTo-X-contaminated gas stream with a biotrickling filter inoculated with microbes bound to a wheat bran/red wood powder/diatomaceous earth carrier. AB - Microbes bound to a wheat bran/red wood powder/diatomaceous earth carrier were used as inoculants for a biotrickling filter (BTF) for treating gases contaminated with a mixture of benzene, toluene, and o-xylene (BTo-X). An overall removal efficiency of more than 87.9% was achieved after a start-up period of as low as 4days. At BTo-X loading rates (LRs) below 60.0g/m(3)h, the BTF's performance was similar for EBRTs of 90, 60, 45 and 30s with an elimination capacity (EC) almost approaching the LR; stable REs above 91.3% for benzene and toluene and above 82.8% for o-xylene were achieved. A maximum EC of 97.7g/m(3)h was obtained at inlet load of 146.4g/m(3)h. The mass ratio of carbon dioxide produced to the BTo-X removed was approximately 2.62, which confirmed complete degradation of BTo-X. The results demonstrate that microbes bound to a solid carrier can be an alternative to traditional liquid inoculums applied in BTFs and highlight their potential applicability to BTF technologies. PMID- 20576427 TI - Effect of harvesting date on the composition and saccharification of Miscanthus x giganteus. AB - The chemical composition of the whole aerial biomass and isolated organs of Miscanthus x giganteus was examined for saccharification into fermentable sugars at early and late harvesting dates. Delayed harvest was mainly related to increased amounts of cell wall and ester-linked phenolic acids. Addition of an enzyme cocktail (cellulases, beta-glucosidase and xylanase) resulted in similar enzyme digestibilities at the two harvesting dates, ranging from 11-13% and 8-9% of the cellulose and arabinoxylan, respectively. However, the internodes, leaves and sheaths varied in cell wall content and composition and gave rise to different saccharification yields with internodes being the most recalcitrant organs. Non-cell wall fraction was estimated as the amount of material extracted by neutral detergent solution, and accounted for 23% of the whole aerial biomass harvested at an early date. However, saccharification yields from the miscanthus biomass did not change after soluble fraction removal. An ammonia pretreatment improved enzyme efficiency on early-harvested miscanthus, to a greater extent than on late-harvested biomass. This trend was confirmed for two different years of harvesting. PMID- 20576428 TI - Enhanced production of dihydroxyacetone from glycerol by overexpression of glycerol dehydrogenase in an alcohol dehydrogenase-deficient mutant of Gluconobacter oxydans. AB - Gluconobacter oxydans can rapidly and incompletely oxidize glycerol to dihydroxyacetone (DHA), a versatile product extensively used in cosmetic, chemical and pharmaceutical industries. To improve DHA production, the glycerol dehydrogenase (GDH) responsible for DHA formation was overexpressed in G. oxydans M5AM, in which the gene coding for the membrane-bound alcohol dehydrogenase (ADH) was interrupted. Real-time PCR and enzyme activity assay revealed that the absence of ADH together with the overexpression of GDH gene resulted in an increased GDH activity in the resulting strain M5AM/GDH, which led to a substantially enhanced production of DHA in a resting cell system. In a batch biotransformation process, M5AM/GDH exhibited a 2.4-fold increased DHA productivity of 2.4g/g CDW/h from 1.0g/g CDW/h, yielding 96g/L DHA from 100g/L glycerol. When 140g/L glycerol was supplied, a final DHA concentration of 134g/L was accumulated within 14h. In four repeated batch runs, 385g DHA over a time period of 34h was achieved from 400g glycerol with an average productivity of 2.2g/g CDW/h. These results indicated that this newly developed strain G. oxydans M5AM/GDH with high productivity and increased tolerance against product inhibition has potential for DHA production in an industrial bioconversion process. PMID- 20576429 TI - Analysis of biological demulsification process of water-in-oil emulsion by Alcaligenes sp. S-XJ-1. AB - A demulsifying strain (S-XJ-1) was isolated from petroleum-polluted soil and identified as Alcaligenes sp. It showed emulsion breaking ratio of 81.3% for W/O emulsion within 24h when the cell concentration was 500mg/L. Evolution of water droplets during the biological demulsification process was investigated using a Turbiscan stability analyzer and microphotography. Further investigation focused on cell surface hydrophobicity and oil-water interfacial properties. The biological demulsification process began with rapid dispersal of the cells into the oil phase and adsorption onto the oil-water interface. This occurred due to high cell surface hydrophobicity and the presence of amphiphilic compounds in the cell walls. The cells had higher interfacial activity than the emulsifier molecules, and they displaced some of the emulsifier molecules, which effectively reduced the interfacial tension gradient. As a result, the interfacial film strength decreased, the water droplets coalesced and eventually phase separation occurred. PMID- 20576430 TI - Propenylamide and propenylsulfonamide cephalosporins as a novel class of anti MRSA beta-lactams. AB - Novel C(3) propenylamide and propenylsulfonamide cephalosporins have been synthesized and tested for their ability to inhibit the penicillin-binding protein 2' (PBP2') from Staphylococcus epidermidis and the growth of a panel of clinically relevant bacterial species, including methicillin-resistant Staphylococcus aureus (MRSA). The most potent compounds inhibited the growth of MRSA strains with minimum inhibitory concentrations (MIC) as low as 1 microg/mL. The structure-activity relationship revealed the potential for further optimization of this new cephalosporin class. PMID- 20576431 TI - Identification of glycosylated exendin-4 analogue with prolonged blood glucose lowering activity through glycosylation scanning substitution. AB - Exendin-4, a glucagon-like peptide 1 receptor agonist, is a potent therapeutic xenopeptide hormone for the treatment of type 2 diabetes. In order to further improve in vivo activity, we examined the introduction of sialyl N acetyllactosamine (sialyl LacNAc) to exendin-4. The glycosylated analogue having sialyl LacNAc at position 28 was found to have improved in vivo activity with prolonged glucose-lowering activity. PMID- 20576432 TI - Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: synthesis, biological evaluation and nitric oxide release studies. AB - A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O(2)-methyl and O(2) acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O(2)-methyl and O(2)-acetoxyethyl compounds was higher (18.0-37.8% of the theoretical maximal release of one molecule of NO/molecule of the parent compound) upon incubation in the presence of rat serum, relative to incubation with phosphate buffer saline (PBS) at pH 7.4 (3.8-11.6% range). All compounds exhibited weak inhibition of the COX-1 isozyme (IC(50)=5.8-17.0 microM range) in conjunction with weak or modest inhibition of the COX-2 isozyme (IC(50)=1.6-14.4 microM range). The most potent AI agent 5-[4-(O(2)-ammonium diazen-1-ium-1,2 diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole exhibited a potency that was about fourfold and twofold greater than that observed for the respective reference drugs aspirin and ibuprofen. These studies indicate that use of a cupferron template constitutes a plausible drug design approach targeted toward the development of AI drugs that do not cause gastric irritation, or elevate blood pressure and induce platelet aggregation that have been associated with the use of some selective COX-2 inhibitors. PMID- 20576433 TI - Synthesis of novel alpha-pyranochalcones and pyrazoline derivatives as Plasmodium falciparum growth inhibitors. AB - Both the lack of a credible malaria vaccine and the emergence and spread of parasites resistant to most of the clinically used antimalarial drugs and drug combination have aroused an imperative need to develop new drugs against malaria. In present work, alpha-pyranochalcones and pyrazoline analogs were synthesized to discover chemically diverse antimalarial leads. Compounds were tested for antimalarial activity by evaluation of the growth of malaria parasite in culture using the microtiter plate based SYBR-Green-I assay. The (E)-3-(3-(2,3,4 trimethoxyphenyl)-acryloyl)-2H-chromen-2-one (Ga6) turned out to be the most potent analog of the series, showing IC(50) of 3.1 microg/ml against chloroquine sensitive (3D7) strain and IC(50) of 1.1 microg/ml against chloroquine-resistant field isolate (RKL9) of Plasmodium falciparum. Cytotoxicity study of the most potent compounds was also performed against HeLa cell line using the MTT assay. All the tested compounds showed high therapeutic indices suggesting that they were selective in their action against the malaria parasite. Furthermore, docking of Ga6 into active site of falcipain enzyme revealed its predicted interactions with active site residues. This is the first instance wherein chromeno pyrazolines have been found to be active antimalarial agents. Further exploration and optimization of this new lead could provide novel, antimalarial molecules which can ward off issues of cross-resistance to drugs like chloroquine. PMID- 20576434 TI - Differentiating Emery-Dreifuss muscular dystrophy and collagen VI-related myopathies using a specific CT scanner pattern. AB - Bethlem myopathy and Ullrich congenital muscular dystrophy are part of the heterogeneous group of collagen VI-related muscle disorders. They are caused by mutations in collagen VI (ColVI) genes (COL6A1, COL6A2, and COL6A3) while LMNA mutations cause autosomal dominant Emery-Dreifuss muscular dystrophy. A muscular dystrophy pattern and contractures are found in all three conditions, making differential diagnosis difficult especially in young patients when cardiomyopathy is absent. We retrospectively assessed upper and lower limb muscle CT scans in 14 Bethlem/Ullrich patients and 13 Emery-Dreifuss patients with identified mutations. CT was able to differentiate Emery-Dreifuss muscular dystrophy from ColVI-related myopathies in selected thigh muscles and to a lesser extent calves muscles: rectus femoris fatty infiltration was selectively present in Bethlem/Ullrich patients while posterior thigh muscles infiltration was more prominently found in Emery-Dreifuss patients. A more severe fatty infiltration particularly in the leg posterior compartment was found in the Emery-Dreifuss group. PMID- 20576435 TI - Investigation of anaphylactic reaction after patent blue V dye injection. AB - BACKGROUND: Patent blue dye V (PBV) is in widespread use for sentinel node biopsy in breast cancer and melanoma. At present, the best diagnostic approach in investigating possible anaphylaxis due to PBV is not defined. METHOD: We reviewed our experience of patients and the cases reported in the literature that developed an anaphylactic reaction after injection of PBV and suggest a diagnostic protocol. From May 2006 to April 2009 six patients were known to the Cardiff anaesthetics department to have suffered a severe anaphylactic reaction after injection of PBV. We amalgamated the results of the investigations of our patients with those of 42 case reports published in the literature during the last 10 years. RESULTS: Of 40 patients with a documented allergy history 31 patients did not have a past medical history of allergy. The median interval between PBV administration and allergic reaction was 15 min (range 1 min-180 min). Of 20 patients with hypotension 18 received inotropes. 4 patients had a fall in blood pressure as their sole symptom. 23 patients had urticaria or other allergic skin manifestations, 8 had blue wheals. 5 patients had bronchospasm. 2 patients had a cardiac arrest. They were successfully resuscitated. The median dose of PBV was 2 ml (range 0.5 ml-5 ml). Tryptase levels were elevated in 14 of 26 tested patients. Skin prick testing was positive in 24 of 30 tested patients. Intradermal testing was positive in all 13 tested patients. CONCLUSION: Most patients experiencing a severe allergic reaction to PBV have no past medical history of allergy. The value of formal allergy skin testing for PBV-related allergy lies in excluding other agents as the causative factor to avoid their exposure in the future. PMID- 20576436 TI - Ambulatory assessment of 3D ground reaction force using plantar pressure distribution. AB - This study aimed to use the plantar pressure insole for estimating the three dimensional ground reaction force (GRF) as well as the frictional torque (T(F)) during walking. Eleven subjects, six healthy and five patients with ankle disease participated in the study while wearing pressure insoles during several walking trials on a force-plate. The plantar pressure distribution was analyzed and 10 principal components of 24 regional pressure values with the stance time percentage (STP) were considered for GRF and T(F) estimation. Both linear and non linear approximators were used for estimating the GRF and T(F) based on two learning strategies using intra-subject and inter-subjects data. The RMS error and the correlation coefficient between the approximators and the actual patterns obtained from force-plate were calculated. Our results showed better performance for non-linear approximation especially when the STP was considered as input. The least errors were observed for vertical force (4%) and anterior-posterior force (7.3%), while the medial-lateral force (11.3%) and frictional torque (14.7%) had higher errors. The result obtained for the patients showed higher error; nevertheless, when the data of the same patient were used for learning, the results were improved and in general slight differences with healthy subjects were observed. In conclusion, this study showed that ambulatory pressure insole with data normalization, an optimal choice of inputs and a well-trained nonlinear mapping function can estimate efficiently the three-dimensional ground reaction force and frictional torque in consecutive gait cycle without requiring a force plate. PMID- 20576437 TI - Incidence and management of high grade glioma in Maori and non-Maori patients. AB - A retrospective analysis of 301 patients was undertaken between 1993 and 2003 to evaluate the relationship of ethnicity with incidence, treatment and survival in patients undergoing surgery for high grade glioma (HGG) in New Zealand. There was no difference in age standardised incidence of HGG in Maori compared to non-Maori patients; 4.2/100,000 person years (95% confidence interval [CI] 2.6-6.9) versus 4.1 (95% CI 3.6-4.6). Maori were more likely to have complete tumour resection (odds ratio 3.59 (95% CI 1.01-12.76)) but waited 1.32 (95% CI 0.98-1.79) times longer for radiotherapy. Median survival was 29 weeks with poorer survival in Maori compared to non-Maori (hazard ratio 1.55 [95% CI 0.95-2.55]). We concluded that the incidence of HGG in Maori is similar to non-Maori. However, Maori with HGG have higher rates of complete resection but wait longer for radiotherapy and may have poorer overall survival than non-Maori. PMID- 20576438 TI - Spectroscopic characterization of the inclusion complexes of luteolin with native and derivatized beta-cyclodextrin. AB - The inclusion complexes of Luteolin (LU) with cyclodextrins (CDs) including beta cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD) and dimethyl beta-cyclodextrin (DMbetaCD), Scheme 1, have been investigated using the method of steady-state fluorescence. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was obtained in the case of HPbetaCD followed by DMbetaCD and betaCD. Moreover, 1H NMR and 2D NMR were carried out, revealing that LU has different form of inclusion which is in agreement with molecular modeling studies. These models confirm that when LU-betaCD and LU-DMbetaCD complexes are formed, the B-ring is oriented toward the primary rim; however, for LU-HPbetaCD complex this ring is oriented toward the secondary rim. The ESR results showed that the antioxidant activity of luteolin was the order LU-HPbetaCD>LU DMbetaCD>LU-betaCD>LU, hence the LU-complexes behave are better antioxidants than luteolin free. PMID- 20576439 TI - STM of isolated complexes of R-Phycoerythrin: direct observation of the gamma subunit at the centre of the complex. AB - Scanning tunnelling microscopy was used to study the topography of single complexes of the photosynthetic protein R-Phycoerythrin and to determine the location of the gamma-subunit. This study has resolved an ambiguity in the positioning of the gamma-subunit from X-ray crystal structure analysis which arose from the symmetry-related averaging of the X-ray diffraction pattern which led to a loss of resolution. PMID- 20576440 TI - Theoretical ELNES using one-particle and multi-particle calculations. AB - One-, two-, and many-particle calculations for electron-energy-loss near-edge structures (ELNES) are reviewed. The most important point for the ELNES calculation is the proper introduction of the core-hole effect. By introducing the core-hole effect in a sufficiently large supercell, one-particle calculations are applicable to the ELNES of many edges. On the other hand, the two-particle interaction between the excited electron and the core-hole, namely the excitonic effect, is significant in the K edges of very light elements and the L(2,3) edges of Mg and Al. Many-particle interactions, including both electron-electron and electron-hole interactions, are indispensable for the L(2,3) edges of transition metals and the M(4,5) edges of lanthanides, namely white lines. In this review, we present the basics, methodologies, and some applications of one-, two-, and many-particle calculations. In addition, importance of momentum transfer vector in the ELNES calculations for comparison with the experiments is discussed. PMID- 20576441 TI - The effect of temperature changes on electrical performance of the betavoltaic cell. AB - There is a significant relationship between temperature and electrical performance of a betavoltaic cell. Two silicon diodes used as energy conversion devices of betavoltaic cells were irradiated by Ni-63, and the relationships between the temperature and the electrical performance such as V(oc), I(sc), and P(max) were examined. I(sc) increased very little as temperature increased but V(oc) decreased considerably. The changing values of V(oc) were -3.1 and -3.0 mV/K, respectively, in the temperature range 233.15-333.15 K. As a result of this, P(max) and eta also decreased markedly. PMID- 20576442 TI - Mega-aorta with aberrant right subclavian artery: use of a novel hybrid technique. AB - A novel approach to the management of aortic arch aneurysm with an aberrant right subclavian artery (ARSA) is described. Construction of a Dacron graft with side arms adapted to the patient's arch anatomy allows for antegrade cerebral perfusion during circulatory arrest and revascularisation of the arch vessels. A long elephant-trunk graft is lowered into the descending aorta using a snare introduced from the femoral artery. Descending aortic stenting can be performed concomitantly or later. Advantages include antegrade cerebral perfusion during arch repair, diminished extent of stenting due to the long elephant trunk, type II endoleak prevention by ARSA ligation and preservation of antegrade flow in the right vertebral artery. PMID- 20576444 TI - In vitro photosensitization initiated by camphorquinone and phenyl propanedione in dental polymeric materials. AB - Documentation is scarce on the photobiological effects of photoinitiators present in dental light curable materials. The aim of this study was to determine cellular effects of the photoinitiators camphorquinone (CQ) and phenyl propanedione (PPD) and to investigate whether these substances produced reactive oxygen species after low and high doses of optical radiation (between 0 and 17J/cm(2)). Rat salivary gland cells in vitro were exposed to visible blue light and/or UVA. Hematoporphyrin (HP), a photosensitizer used in medicine, and the UVA filter 2-methoxy-4-hydroxy-benzophenone (B-3) were used as reference substances. It was found that PPD produced hydrogen peroxide, but not singlet oxygen, upon light irradiation. CQ produced neither hydrogen peroxide nor singlet oxygen. Cell death by necrosis and apoptosis was induced by irradiation in the presence of CQ, PPD and HP. Doses higher than 6J/cm(2) UVA and blue visible light from a source similar to clinically applied sources, induced apoptosis even in the absence of photosensitizers added. A reciprocity relationship was found between radiant exposure (at constant irradiance) and concentration of photoinitiators. In conclusion, the oral cells under investigation were light sensitive, and the sensitivity increased in presence of photoinitiators. PPD acted by mechanisms that included reactive oxygen species and CQ probably by formation of free radicals. PMID- 20576443 TI - The autologous pleural buttressing of staple lines in surgery for bullous lung disease. AB - OBJECTIVE: Prolonged air leak remains as one of the most common complications after surgery for bullous lung disease. Reinforcement of the staple line with either prosthetic material or bovine pericardial strips has been advocated to avoid this problem. We used the patients' own parietal pleural layer to cover the staple lines to prevent air leak and subsequently assessed the comparative results. METHODS: A total of 22 patients underwent thoracotomy for bullous lung disease, mainly due to lobe-dominance bullae combined with emphysema, between November 2006 and November 2008. A case-control study was set from the surgical data of patients who were operated on using stapling devices without any buttressing material (group I=12) and were compared with the group of patients who were operated on using staplers buttressed with an autologous pleural layer (group II=10). Patient characteristics, chest-tube removal time and length of hospital stay were prospectively recorded in group II. The outcomes of the two groups were analysed based on postoperative complications, chest-tube removal time and postoperative length of hospital stay. RESULTS: There was no statistically significant difference between both the groups in preoperative characteristics including age, sex, co-morbid factors, and respiratory functions, heterogeneity of emphysema, intra-operative adhesion density and length of staple line. However, the chest tube was removed significantly earlier in patients whose bullae were resected by stapling devices buttressed with autologous-parietal pleura (p=0.04). CONCLUSIONS: Autologous pleural reinforcement of the staple line in surgery for bullous lung disease is a safe, effective and cost-free procedure that precipitates the early removal of the chest tube. PMID- 20576445 TI - Determination of body weight and height measurement for critically ill patients admitted to the intensive care unit: A quality improvement project. AB - PURPOSE: Measuring body weight and height of critically ill patients in intensive care often challenge nurses. Estimated weight and height is thought to be inaccurate. This quality improvement project was to determine one effective method of how all patients in intensive care unit (ICU) could be measured and weighed accurately and cost effectively. The determined method also was to be Occupation Health and Safety safe, adhere to infection control standards and minimises risks of patient handling. The focus for this quality improvement was that the measurement methods were to be utilised in conjunction with a baseline patient assessment in the ICU. METHODS: Six different types of weighing scales were compared. Three methods were tested in a workshop for accuracy. The results were compared to a 'standing scale' as the 'gold standard' for body weight. The second stage of the project was to determine the body height of patients in the supine position. The tools were designed by the quality improvement team (QIT) and manufactured by the hospital Departments. The methods were also tested in a workshop for accuracy. The measurements were compared to a wall mounted stadiometer as the 'gold standard'. RESULTS: The two height measurement tools displayed differences of -1.2 to +3cm. The first weighing results of three methods showed variations. The methods displayed differences from 0.8 to 25kg. The aluminium height measurement tools and the Mercury scale conformed to the standard agreed to by the QIT. DISCUSSION: Staff in the ICU required minimal training for the methods used. The uptake of a measured weight and height, in difference to estimation takes some time for staff to accept and use. Case exemplars that demonstrated an error rate with estimation were useful feedback towards the change in practice. CONCLUSION: It was found that critically ill patients could be weighed effectively and accurately with a scale usable for every type of bed available in this ICU. All supine positioned patients can also be measured effectively and accurately with one height measurement method. These methods do not require the patient to be moved. There is no need to disconnect lines or monitoring equipment at any time during the measuring procedures. PMID- 20576446 TI - In-hospital mortality in acute ischemic stroke treated with hemicraniectomy in US hospitals. AB - Hemicraniectomy is a surgical procedure performed to prevent cerebral herniation and death in patients who have sustained a massive ischemic stroke in the anterior circulation territory. Information on in-hospital mortality in patients with large ischemic stroke treated with hemicraniectomy outside randomized trials is lacking. We sought to identify in-hospital mortality associated with hemicraniectomy in a large US sample. We selected our cohort from the National Inpatient Sample database for the years 2000 through 2006 using the clinical classification software codes for acute ischemic stroke (AIS) and arterial occlusion, and identified those patients treated with thrombolysis or hemicraniectomy by the procedure codes. A multivariate logistic regression model was used for adjusted analysis. Among 502,231 patients with AIS, 252 (0.05%) underwent hemicraniectomy, and 7526 (1.5%) were treated with thrombolysis. Compared with the nonsurgical group, patients treated with hemicraniectomy were younger (mean age, 55.6 vs 71.5 years) and had lower Charlson Comorbidity Index scores (92.8% vs 76.0%). The mortality rate was higher in the hemicraniectomy group (32.1% vs 10.8%; adjusted odds ratio [OR] = 3.91; 95% confidence interval [CI] = 2.97-5.16). In patients treated with thrombolysis, mortality was higher in the hemicraniectomy group compared with the nonsurgical group (35.3% vs 13.1%; P = .01). The rate of hospital utilization of hemicraniectomy varied between 0.04% and 0.06% among all stroke admissions; the trend did not change significantly over the 7-year study period (P = .06). The mortality rate in hemicraniectomy treated patients was significantly lower than in historical cohorts however, hemicraniectomy remains associated with high in-hospital mortality. The rate of utilization of hemicraniectomy for AIS in US hospitals has remained essentially unchanged. PMID- 20576447 TI - Periosteal chondrosarcoma of the foot: a case report. AB - A 19-year-old girl presented with painless swelling of the first left toe of 6 years' duration. Magnetic resonance imaging (MRI) of the lesion demonstrated a soft tissue mass adjacent to the surface of the bone with slight erosion of the underlying cortex. Surgical excision was performed and the histopathological diagnosis was low-grade periosteal chondrosarcoma, which is quite uncommon in this location. PMID- 20576448 TI - Hourglass ganglion cyst of the foot: a case report. AB - Ganglion cyst, a common benign soft tissue lesion, is not uncommon in the foot, with the most common location being the dorsal aspect. We describe a case where the ganglion had an unusual radiographic appearance in the form of an hourglass, extending from dorsum into the planter compartments of the foot. A 74-year-old woman presented with longstanding pain in her midfoot. Clinical examination revealed a soft tissue swelling with minimal tenderness in the first webspace of the right foot. The initial radiograph was normal. Ultrasound examination revealed a cystic swelling filled with hemorrhagic fluid with an hourglass appearance. Magnetic resonance imaging examination confirmed the cystic nature of the swelling and depicted the hourglass-shaped ganglion extending from the dorsal to plantar aspect of foot. Complete excision was possible with a combined dorsal and plantar approach. Ganglion cyst can present in the foot in locations other than the dorsum and could have extensions into the plantar aspect. This variation needs to be considered when planning surgical excision, which could be aided by preoperative magnetic resonance imaging. PMID- 20576449 TI - Delayed rupture of the extensor hallucis longus and extensor digitorum communis tendons after breaching the anterior capsule with a radiofrequency probe during ankle arthroscopy: a case report. AB - A 40-year-old man with early arthritis, loose bodies, and anterolateral joint impingement symptoms in his left ankle, which was refractory to noninvasive therapeutic modalities for 1 year, underwent ankle arthroscopy and radiofrequency thermal ablation. The anterior capsule of the ankle joint was breached by the radiofrequency probe while the loose bodies were removed from the anterior recess, exposing the extensor tendons and resulting in a delayed spontaneous rupture of the extensor hallucis longus tendon and extensor tendons to the second and third toes. The extensor hallucis longus tendon was repaired with a semitendinosus tendon graft, and extensor digitorum tendons underwent primary repair. The patient regained full function and was symptom free 1 year after surgery. PMID- 20576450 TI - Automated CT scoring of airway diseases: preliminary results. AB - RATIONALE AND OBJECTIVES: The aim of this study was to retrospectively evaluate an automated global scoring system for evaluating the extent and severity of disease in a known cohort of patients with documented bronchiectasis. On the basis of a combination of validated three-dimensional automated algorithms for bronchial tree extraction and quantitative airway measurements, global scoring combines the evaluation of bronchial lumen-to-artery ratios and bronchial wall-to artery ratios, as well as the detection of mucoid-impacted airways. The result is an automatically generated global computed tomographic (CT) score designed to simplify and standardize the interpretation of scans in patients with chronic airway infections. MATERIALS AND METHODS: Twenty high-resolution CT data sets were used to evaluate an automated CT scoring method that combines algorithms for airway quantitative analysis that have been individually tested and validated. Patients with clinically documented atypical mycobacterial infections with visually assessed CT evidence of bronchiectasis varying from mild to severe were retrospectively selected. These data sets were evaluated by two independent experienced radiologists and by computer scoring, with the results compared statistically, including Spearman's rank correlation. RESULTS: Computer evaluation required 3 to 5 minutes per data set, compared to 12 to 15 minutes for manual scoring. Initial Spearman's rank tests showed positive correlations between automated and readers' global scores (r = 0.609, P = .01), extent of bronchiectasis (r = 0.69, P = .0004), and severity of bronchiectasis (r = 0.61, P = .01), while mucus plug detection showed a lesser extent of positive correlation between the scoring methods (r = 0.42, P = .07) and wall thickness a negative weak correlation (r = -0.10, P = .40). Further retrospective review of 24 lobes in which wall thickness scores showed the highest discrepancy between manual and automated methods was then performed, using electronic calipers and perpendicular cross-sections to reassess airway measurements. This resulted in an improved Spearman's rank correlation to r = 0.62 (P = .009), for a global score of r = 0.67 (P = .001). CONCLUSION: Automated computerized scoring shows considerable promise for providing a standardized, quantitative method, demonstrating overall good correlation with the results of experienced readers' evaluation of the extent and severity of bronchiectasis. It is speculated that this technique may also be applicable to a wide range of other conditions associated with chronic bronchial inflammation, as well as of potential value for monitoring response to therapy in these same populations. PMID- 20576451 TI - Accuracy of FDG-PET-CT in the diagnostic work-up of vascular prosthetic graft infection. AB - OBJECTIVES: To investigate the diagnostic accuracy of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) compared with computed tomography (CT) scanning and added value of fused FDG-PET-CT in diagnosing vascular prosthetic graft infection. DESIGN: Prospective cohort study with retrospective analysis. MATERIALS: Twenty five patients with clinically suspected vascular prosthetic infection underwent CT and FDG-PET scanning. METHODS: Two nuclear medicine physicians assessed the FDG-PET scans; all CT scans were assessed by two radiologists. Fused FDG-PET/CT were judged by the radiologist and the nuclear medicine physician. The concordance between CT and FDG-PET and the inter-observer agreement between the different readers were investigated. RESULTS: Fifteen patients had a proven infection by culture. Single FDG-PET had the best results (sensitivity 93%, specificity 70%, positive predictive value 82% and negative predictive value 88%). For CT, these values were 56%, 57%, 60% and 58%, respectively. Fused CT and FDG-PET imaging also showed high sensitivity and specificity rates and high positive and negative values. Inter-observer agreement for FDG-PET analysis was excellent (kappa = 1.00) and moderate for CT and fused FDG-PET-CT analysis (0.63 and 0.66, respectively). CONCLUSION: FDG-PET scanning showed a better diagnostic accuracy than CT for the detection of vascular prosthetic infection. This study suggests that FDG-PET provides a useful tool in the work-up for diagnosis of vascular prosthetic graft infection. PMID- 20576452 TI - Experimental evaluation of acute molding of the regenerate in mandibular distraction osteogenesis in a rabbit model. AB - OBJECTIVES: The aim of this study was to investigate the possible effect of acute regenerate molding (ARM) on bone healing in mandibular distraction osteogenesis (DO). STUDY DESIGN: Nine white New Zealand rabbits underwent unilateral mandibular lengthening via DO. Three groups were created: The first underwent 15 degrees ARM, the second group underwent 30 degrees ARM after the distraction period, and the third group served as control without molding. After 1 month of consolidation, all of the animals were killed and histomorphometric evaluation was performed. RESULTS: New bone formation was uneventful in all of the groups. In the ARM groups, the amounts of osteoblasts and newly formed bone areas were higher in compressed areas than in stretched ones (P < .05). The regenerates in the control group and stretched regenerate areas of the ARM groups were similar regarding new bone formation (P > .05). CONCLUSION: Acute regenerate molding could be safely applied immediately after the distraction period to correct postdistraction deformities without compromising bone healing. PMID- 20576453 TI - Differences in the outer membrane-related properties of the six classical Brucella species. AB - Outer membrane-related properties (such as auto-agglutination and susceptibility to various compounds) of strains representative of the six classical species of the genus Brucella were assessed. The differences identified could not be fully explained based on the smooth or rough phenotype of the strain. Smooth strains of the closely related species Brucella melitensis and B. abortus exhibited different susceptibility patterns and the rough, virulent B. ovis and B. canis strains were equally or more resistant to conditions such as pH, non-immune serum, hydrogen peroxide and bactericidal cationic peptides than smooth strains. Such heterogeneity in outer membrane characteristics could account for differences in pathogenicity and host tropism. PMID- 20576454 TI - The application of frequency swept pulses for the acquisition of nuclear quadrupole resonance spectra. AB - The acquisition of nuclear quadrupole resonance (NQR) spectra with wideband uniform rate and smooth truncation (WURST) pulses is investigated. (75)As and (35)Cl NQR spectra acquired with the WURST echo sequence are compared to those acquired with standard Hahn-echo sequences and echo sequences which employ composite refocusing pulses. The utility of WURST pulses for locating NQR resonances of unknown frequency is investigated by monitoring the integrated intensity and signal to noise of (35)Cl and (75)As NQR spectra acquired with transmitter offsets of several hundreds kilohertz from the resonance frequencies. The WURST echo sequence is demonstrated to possess superior excitation bandwidths in comparison to the pulse sequences which employ conventional monochromatic rectangular pulses. The superior excitation bandwidths of the WURST pulses allows for differences in the characteristic impedance of the receiving and excitation circuits of the spectrometer to be detected. Impedance mismatches have previously been reported by Marion and Desvaux [D.J.Y. Marion, H. Desvaux, J. Magn. Reson. (2008) 193(1) 153-157] and Muller et al. [M. Nausner, J. Schlagnitweit, V. Smrecki, X. Yang, A. Jerschow, N. Muller, J. Magn. Reson. (2009) 198(1) 73-79]. In this regard, WURST pulse sequences may afford an efficient new method for experimentally detecting impedance mismatches between receiving and excitation circuits, allowing for the optimization of solids and solution NMR and NQR spectrometer systems. The use of the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence for signal enhancement of NQR spectra acquired with WURST pulses and conventional pulses is also investigated. Finally, the utility of WURST pulses for the acquisition of wideline NQR spectra is demonstrated by acquiring part of the (63/65)Cu NQR spectrum of CuCN. PMID- 20576455 TI - Mellin transform of CPMG data. AB - This paper describes a new method for computing moments of the transverse relaxation time T(2) from measured CPMG data. This new method is based on Mellin transform of the measured data and its time-derivatives. The Mellin transform can also be used to compute the cumulant generating function of lnT(2). The moments of relaxation time T(2) and lnT(2) are related to petro-physical and fluid properties of hydrocarbons in porous media. The performance of the new algorithm is demonstrated on simulated data and compared to results from the traditional inverse Laplace transform. Analytical expressions are also derived for uncertainties in these moments in terms of the signal-to-noise ratio of the data. PMID- 20576456 TI - Increased class A scavenger receptor and glomerular lipid precede mesangial matrix expansion in the bGH mouse model. AB - OBJECTIVE: Elevated neutral lipid content and mRNA expression of class A scavenger receptor (SRA) have been found in the renal cortex of the bovine growth hormone (bGH) mouse model of progressive glomerulosclerosis (GS). We hypothesize that the increased expression of SRA precedes glomerular scarring in this model. DESIGN: Real time RT-PCR and immunofluorescence were employed to measure SRA and collagen types I and IV in the bGH transgenic and control mice at 5 and 12 weeks (wk) of age to determine the chronology of change in SRA expression in relation to glomerular scarring. Alternative mechanisms for increasing glomerular lipid were assessed by measuring mRNA expression levels of low-density lipoprotein receptor (LDL-r), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and ATP binding cassette transporter A1 (ABCA1). In addition, the involvement of macrophages in early GS was assessed by CD68 mRNA expression in kidney cortex. RESULTS: Both mRNA and protein levels of SRA were significantly increased in 5-wk bGH compared with control mice, whereas the expression of collagen I and IV was unaltered. Unchanged levels of LDL-r and HMGR mRNA indicate that neither regulated cholesterol uptake via LDL-r nor the cholesterol synthetic pathway played a role in the early lipid increase. The finding of increased ABCA1 expression was an indicator of excess intracellular lipid in the renal cortex of bGH mice at 5 wk. CD68 expression in bGH did not differ significantly from that of controls at 5 wk suggesting that cortical macrophage infiltration was not increased in bGH mice at this time point. CONCLUSION: An early increase in SRA mRNA and protein expression in the bGH kidney precedes glomerular scarring and is independent of macrophage influx. PMID- 20576457 TI - [Preconception care]. AB - The preconception care has been defined as reporting high-risk situations for future pregnancy, and management of those situations. Personal and family history, physical exam, laboratory screening, vaccination, nutrition supplements, and injury prevention should be reviewed in all women. PMID- 20576458 TI - [Recurrent adnexal torsion with normal ovarian, in the second and third trimesters of pregnancy]. AB - We report the only case of recurrent bilateral adnexal torsion during pregnancy with normal ovaries. This rare situation raises diagnostic as well as therapeutic management difficulties. PMID- 20576459 TI - An adaptive Kalman-based Bayes estimation technique to classify locomotor activities in young and elderly adults through accelerometers. AB - An accelerometer-based system able to classify among different locomotor activities during real life conditions is here presented, and its performance evaluated. Epochs of walking at different speeds, and with different slopes, and stair descending and ascending, are detected, segmented, and classified by using an adaptation of a naive 2D-Bayes classifier, which is updated on-line through the history of the estimated activities, in a Kalman-based scheme. The feature pair used for classification is mapped from an ensemble of 16 features extracted from the accelerometer data for each activity epoch. Two different versions of the classifier are presented to combine the multi-dimensional nature of the accelerometer data, and their results are compared in terms of correct recognition rate of the segmented activities, on two population samples of different age. The classification algorithm achieves correct classification rates higher than 90% and higher than 92%, for young and elderly adults, respectively. PMID- 20576460 TI - Smoking in urban outdoor public places: Behaviour, experiences, and implications for public health. AB - This paper identifies factors that influence where people smoke outdoors and examines the impact of smoking on people who use outdoor public places. Direct observations of smoking at 12 outdoor public places and semi-structured interviews with 35 non-smoking and smoking adults were used to gather information in Toronto, Canada, about where people smoke, and smoking related behaviours, perspectives, and experiences. Observation and interview data show that smoking at building entrances was problematic. In total, approximately 37% of smoking observed across the sites was within 9m of building entrances. Shelter, convenience, the social culture of smoking, visibility, and the presence of non smokers were key factors that influenced where people smoked. Clearly defined rules for smoking at building entrances may allow users of public spaces to avoid tobacco smoke when entering and exiting. However, further research is needed regarding the effectiveness of outdoor restrictions and potential unintended consequences. PMID- 20576461 TI - A study to explore the reliability and precision of intra and inter-rater measures of ULNT1 on an asymptomatic population. AB - Upper Limb Neurodynamic Test 1 (ULNT1) is commonly used within clinical practice. However, the existing evidence regarding its reliability is conflicting and raises methodological questions. Therefore, the aim of this study was to investigate how reliable and precise physiotherapists are at recording both intra and inter-rater measurements of ULNT1 on an asymptomatic population. Forty asymptomatic subjects, 29 females and 11 males (18-42 years, mean 23.35), were recruited into this intra (stability) and inter-rater (equivalence) reliability and precision study. ULNT1 was recorded twice using an electrogoniometer by two experienced physiotherapists using a standardised operational description in conditions replicating clinical practice. Reliability was analysed using the Intraclass Correlation Coefficient (ICC2,1), and precision using Standard Error of Measurement (SEM) and Smallest Detectable Difference (SDD). The findings demonstrated excellent intra-rater (ICC2,1 0.98 Rater 1; ICC2,1) 0.96 Rater 2) and good inter-rater (ICC2,1 0.80) reliability. Precision was acceptable for both intra-rater (SEM 2.59 degrees Rater 1; SEM 0.97 degrees Rater 2; SDD 7.16 degrees Rater 1; SDD 2.68 degrees Rater 2), and inter-rater (SEM 3.83 degrees ; SDD 10.58 degrees ) measurements. These findings demonstrate that physiotherapists can use ULNT1 reliably and with precision for intra and inter rater measurements of asymptomatic subjects in conditions that replicate clinical practice. The reproduction of this study on a population of symptomatic subjects is now warranted. PMID- 20576462 TI - A randomised controlled study examining the short-term effects of Strain Counterstrain treatment on quantitative sensory measures at digitally tender points in the low back. AB - Strain-Counterstrain (SCS) intervention has been claimed to elicit immediate and sustained reductions in tenderness at digitally tender points (DTPs), however, there is little experimental evidence to support this. Twenty-eight volunteer participants with low back pain--LBP (17 females and 11 males with mean [SD] age of 39.2 [11.1] and Oswestry disability index of 15.7 [8.6]) participated in this controlled, within-participants study of the immediate and short-term effects of SCS intervention, on pressure pain threshold (PPT) electrical detection threshold (EDT) and electrical pain threshold (EPT) at DTPs in the low back region. Immediate increases in PPT at DTPs were found following all interventions; control intervention: 30.7 kPa [CI 95% - 3.3-64.8] (p = 0.041), sham-SCS intervention: 48.2kPa [CI 95% 14.8-81.7] (p = 0.008) and SCS intervention: 93.4kPa [CI 95% 60.0-126.9] (p<0.0001). Results suggest that SCS intervention does elicit an immediate quantifiable reduction in tenderness at DTPs but that some of this reduction is attributable to the manual-contact component of the treatment. Increases in PPT at DTPs following SCS intervention did not appear to be maintained between 24 and 96 h after treatment. A further finding was that the control intervention elicited significant increases in both EDT (p = 0.044) and EPT (p = 0.026). The explanation for these findings is unclear. PMID- 20576463 TI - Atlas-based whole-body segmentation of mice from low-contrast Micro-CT data. AB - This paper presents a fully automated method for atlas-based whole-body segmentation in non-contrast-enhanced Micro-CT data of mice. The position and posture of mice in such studies may vary to a large extent, complicating data comparison in cross-sectional and follow-up studies. Moreover, Micro-CT typically yields only poor soft-tissue contrast for abdominal organs. To overcome these challenges, we propose a method that divides the problem into an atlas constrained registration based on high-contrast organs in Micro-CT (skeleton, lungs and skin), and a soft tissue approximation step for low-contrast organs. We first present a modification of the MOBY mouse atlas (Segars et al., 2004) by partitioning the skeleton into individual bones, by adding anatomically realistic joint types and by defining a hierarchical atlas tree description. The individual bones as well as the lungs of this adapted MOBY atlas are then registered one by one traversing the model tree hierarchy. To this end, we employ the Iterative Closest Point method and constrain the Degrees of Freedom of the local registration, dependent on the joint type and motion range. This atlas-based strategy renders the method highly robust to exceptionally large postural differences among scans and to moderate pathological bone deformations. The skin of the torso is registered by employing a novel method for matching distributions of geodesic distances locally, constrained by the registered skeleton. Because of the absence of image contrast between abdominal organs, they are interpolated from the atlas to the subject domain using Thin-Plate-Spline approximation, defined by correspondences on the already established registration of high contrast structures (bones, lungs and skin). We extensively evaluate the proposed registration method, using 26 non-contrast-enhanced Micro-CT datasets of mice, and the skin registration and organ interpolation, using contrast-enhanced Micro CT datasets of 15 mice. The posture and shape varied significantly among the animals and the data was acquired in vivo. After registration, the mean Euclidean distance was less than two voxel dimensions for the skeleton and the lungs respectively and less than one voxel dimension for the skin. Dice coefficients of volume overlap between manually segmented and interpolated skeleton and organs vary between 0.47+/-0.08 for the kidneys and 0.73+/-0.04 for the brain. These experiments demonstrate the method's effectiveness for overcoming exceptionally large variations in posture, yielding acceptable approximation accuracy even in the absence of soft-tissue contrast in in vivo Micro-CT data without requiring user initialization. PMID- 20576464 TI - Seeing other minds: attributed mental states influence perception. AB - A current consensus views social perception as a bottom-up process in which the human brain uses social signals to make inferences about another's mental state. Here we propose that, contrary to this model, even the most basic perceptual processing of a social stimulus and closely associated automatic responses are modulated by mental-state attribution. We suggest that social perception is subserved by an interactive bidirectional relationship between the neural mechanisms supporting basic sensory processing of social information and the theory-of-mind system. Consequently, processing of a social stimulus cannot be divorced from its representation in terms of mental states. This hypothesis has far-reaching implications for our understanding of both the healthy social brain and characteristic social failures in psychopathology. PMID- 20576465 TI - Probabilistic models of cognition: exploring representations and inductive biases. AB - Cognitive science aims to reverse-engineer the mind, and many of the engineering challenges the mind faces involve induction. The probabilistic approach to modeling cognition begins by identifying ideal solutions to these inductive problems. Mental processes are then modeled using algorithms for approximating these solutions, and neural processes are viewed as mechanisms for implementing these algorithms, with the result being a top-down analysis of cognition starting with the function of cognitive processes. Typical connectionist models, by contrast, follow a bottom-up approach, beginning with a characterization of neural mechanisms and exploring what macro-level functional phenomena might emerge. We argue that the top-down approach yields greater flexibility for exploring the representations and inductive biases that underlie human cognition. PMID- 20576466 TI - Pilot implementation of health information systems: issues and challenges. AB - OBJECTIVES: This study aims to explore the issues and challenges involved in designing and organizing pilot implementations of health information systems (HIS). Pilot implementations are a widely used approach for identifying design flaws and implementation issues before full-scale deployment of new HIS. However, it is not uncommon for pilot implementations to fail in the sense that little can be learned from them. METHOD: We employed an interpretive case study approach in attempting to throw light on the reasons why pilot implementations sometimes fail. We studied the (failed) pilot implementation of an electronic Pregnancy Record (ePR) in Denmark. Our primary data collection methods comprised participant observations, semi-structured interviews and document analyses. RESULTS: Based on a comprehensive evaluation of the implementation process, we identify three major challenges that complicated the pilot project and eventually led to its failure, namely difficulties in (1) defining an appropriate scope for the pilot implementation, (2) coping with unanticipated technical and practical problems, and (3) ensuring commitment from test users and their managers. CONCLUSION: Pilot implementations are a very useful technique for developing HIS, but also one that is very difficult to do successfully. It is sometimes assumed that pilot implementations are less complicated and risky than regular, full scale implementations. However, pilot implementations are not just small-scale versions of conventional implementations; they are fundamentally different and they have their own complications and issues to deal with that make them hard to design and manage. PMID- 20576467 TI - Combination of cytomegalovirus enhancer with human cellular promoters for gene induced chondrogenesis of human bone marrow mesenchymal stem cells. AB - High-expression plasmid vectors for human mesenchymal stem cells (MSCs) were constructed by combination of cytomegalovirus immediate-early enhancer with cellular promoters. MSCs transfected with the vector showed higher transgene production of a cytokine, which increased the differentiation level to chondrocytes. PMID- 20576468 TI - FADD: a regulator of life and death. AB - FAS-associated protein with death domain (FADD) is the key adaptor protein transmitting apoptotic signals mediated by the main death receptors (DRs). Besides being an essential instrument in cell death, FADD is also implicated in proliferation, cell cycle progression, tumor development, inflammation, innate immunity, and autophagy. Recently, many of these new functions of FADD were shown to be independent of DRs. Moreover, FADD function is dictated by protein localization and phosphorylation state. Thus, FADD is a crucial and unique controller of many essential cellular processes. The full understanding of the networks dictating the ultimate function of FADD may provide a new paradigm for other multifaceted proteins. PMID- 20576470 TI - Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective. AB - OBJECTIVE: To evaluate outcomes of desmopressin treatment in monosymptomatic enuresis (ME) and nonmonosymptomatic enuresis (NME). MATERIALS AND METHODS: PubMed was searched for all studies investigating enuresis, up to July 2009, in which desmopressin was administered alone or combined with other treatments. Each study was graded according to its respective level of evidence. RESULTS: Altogether, 99 studies enrolling 7422 patients were identified as fulfilling the inclusion criteria. In 76 studies, desmopressin was administered as monotherapy; in 29 it was combined with other treatments such as antimuscarinics and enuresis alarm. CONCLUSION: Studies incorporating a minor invasive versus a non-invasive diagnostic approach seem to achieve superior long-term success rates. Primary efficacy outcomes following desmopressin treatment are more favourable in ME than NME. Desmopressin administered with adjunct measures achieves superior outcomes compared to monotherapy, especially in NME. Compared to sudden withdrawal, the structured withdrawal programs show better long-term success and lower relapse rates. So far, no superiority has been shown for either time- or dose-dependent structured withdrawal programs. Most studies incorporated only small case series; only 25 studies with level of evidence 1 or 2 have been conducted. The broad range of mono- and adjunct treatments were evaluated according to the evidence based criteria recommended by the European Association of Urology. PMID- 20576469 TI - Cystic kidney disease: the role of Wnt signaling. AB - Wnt signaling encompasses a variety of signaling cascades that can be activated by secreted Wnt ligands. Two such pathways, the canonical or beta-catenin pathway and the planar cell polarity (PCP) pathway, have recently received attention for their roles in multiple cellular processes within the kidney. Both of these pathways are important for kidney development as well as homeostasis and injury repair. The disruption of either pathway can lead to cystic kidney disease, a class of genetic diseases that includes the most common hereditary life threatening syndrome polycystic kidney disease (PKD). Recent evidence implicates canonical and noncanonical Wnt pathways in cyst formation and points to a remarkable role for developmental processes in the adult kidney. PMID- 20576472 TI - Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions: pilot study. AB - STUDY OBJECTIVE: To estimate the efficacy of fresh and dried amnion graft after hysteroscopic lysis of severe intrauterine adhesions in decreasing its recurrence and encouraging endometrial regeneration. DESIGN: Pilot prospective randomized comparative study (Canadian Task Force classification I). SETTING: Ain Shams Medical School, Cairo, Egypt. PATIENTS: Forty-five patients with severe intrauterine adhesions. Primary symptom was infertility with or without menstrual disorders such as amenorrhea or hypomenorrhea. INTERVENTIONS: Patients were randomized preoperatively using a computer-generated randomization sheet into 3 groups of 15 patients each. Allocation to any group was concealed in an opaque envelope, which was opened at the time of operation. Hysteroscopic lysis of intrauterine adhesions was followed by insertion of an intrauterine balloon only (group 1) or either fresh amnion graft (group 2) or dried amnion graft (group 3) for 2 weeks. Diagnostic hysteroscopy was performed at 2 to 4 months postoperatively. MEASUREMENTS AND MAIN RESULTS: Adhesion grade, menstruation, uterine length, complications, and reproductive outcome were determined. There was significant improvement in adhesion grade with amnion graft vs intrauterine balloon alone (p = .003). Improvement was greater with fresh amnion than with dried amnion (p = .01). Normal menstruation occurred in 4 patients (28.6%) in group 1, 5 (35.7%) in group 2, and 7 (46.7%) in group 3. Of 43 patients, 41 (95.3%) were treated in 2 endoscopic sessions (95.3%), and 2 patients (4.7%) were treated in 3 endoscopic sessions. Uterine perforations occurred in 2 patients (4.7%), and cervical tears in 3 (7.0%). Ten patients (23.3%) achieved pregnancy, 8 (80%) after amnion graft and 2 (20%) without amnion. Six of the 10 patients (60%) miscarried, and 4 (40%) were either still pregnant or delivered at term without complications. CONCLUSION: Hysteroscopic lysis of severe intrauterine adhesions with grafting of either fresh or dried amnion is a promising adjunctive procedure for decreasing recurrence of adhesions and encouraging endometrial regeneration. PMID- 20576473 TI - Single-port laparoscopic myomectomy using a new single-port transumbilical morcellation system: initial clinical study. AB - STUDY OBJECTIVE: To evaluate the feasibility of single-port laparoscopic myomectomy with transumbilical morcellation and suturing. DESIGN: Continuing prospective study (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Fifteen patients who underwent single-port laparoscopic myomectomy between September 2008 and October 2009 to remove single or multiple uterine myomas, at least 1 in each patient measuring greater than 4 cm in diameter. INTERVENTIONS: All single-port laparoscopic myomectomy procedures were performed by a single surgeon (Dr. Y.W. Kim). Myomas were extracted transumbilically by cutting the myomas into smaller pieces with a knife or a conventional electromechanical morcellator. After making a single 1.5- to 2.0-cm umbilical incision, the single-port system, created with a wound retractor and a surgical glove, was inserted. All operations were performed using conventional rigid straight laparoscopic instruments. Laparoscopic suturing was performed in intramural myomas and some subserosal myomas. MEASUREMENTS AND MAIN RESULTS: Patient mean (SD; range) age was 38.3 (5.6; 29-49) years. The number of myomas per patient was 1.6 (1.4; 1-6). The diameter of the largest myomas was 6.1 (1.5; 4.2-9.6) cm. In 4 patients, only a knife was required for transumbilical extraction of myomas, and in 11 patients, transumbilical morcellation with an electromechanical morcellator with or without a knife was used. Transumbilical drainage tubes were inserted into the pelvic cavity in 11 of 15 patients. Operative time was 96.7 (33.8; 35-150) minutes. The decrease in postoperative hemoglobin concentration was 1.8 (1.2; 0.4-3.6) g/dL. During the operations, no patients required blood transfusion. No patients developed postoperative fever. Neither bowel injury nor urinary tract injury occurred in any patient. The postoperative hospital stay was 3.1 (0.8; 2-4) days. CONCLUSION: Single-port transumbilical morcellation using a conventional electromechanical morcellator with or without a knife is feasible. Single-port laparoscopic myomectomy is an alternative method with cosmetic advantage. PMID- 20576474 TI - Optimization and quality assessment of the post-digestion 18O labeling based on urea for protein denaturation by HPLC/ESI-TOF mass spectrometry. AB - The post-digestion (18)O labeling method decouples protein digestion and peptide labeling. This method allows labeling conditions to be optimized separately and increases labeling efficiency. A common method for protein denaturation in proteomics is the use of urea. Though some previous studies have used urea-based protein denaturation before post-digestion (18)O labeling, the optimal (18)O labeling conditions in this case have not been yet reported. Present study investigated the effects of urea concentration and pH on the labeling efficiency and obtained an optimized protocol. It was demonstrated that urea inhibited (18)O incorporation depending on concentration. However, a urea concentration between 1 and 2M had minimal effects on labeling. It was also demonstrated that the use of FA to quench the digestion reaction severely affected the labeling efficiency. This study revealed the reason why previous studies gave different optimal pH for labeling. They neglect the effects of different digestion conditions on the labeling conditions. Excellent labeling quality was obtained at the optimized conditions using urea 1-2 M and pH 4.5, 98.4+/-1.9% for a standard protein mixture and 97.2+/-6.2% for a complex biological sample. For a 1:1 mixture analysis of the (16)O- and (18)O-labeled peptides from the same protein sample, the average abundance ratios reached 1.05+/-0.31, demonstrating a good quantitation quality at the optimized conditions. This work will benefit other researchers who pair urea-based protein denaturation with a post-digestion (18)O labeling method. PMID- 20576475 TI - Predictable and linear scale-up of four phenolic alkaloids separation from the roots of Menispermum dauricum using high-performance counter-current chromatography. AB - This paper describes how distribution ratios were used for prediction of peak elution in analytical high-performance counter-current chromatography (HPCCC) to explore the method for separation and purification of bioactive compounds from the roots of Menispermum dauricum. Then important parameters related to HPCCC separations including solvent systems, sample concentration, sample loading volume and flow rate were optimized on an analytical Mini-DE HPCCC and finally linearly scaled up to a preparative Midi-DE HPCCC with nearly the same resolutions and separation time. Four phenolic alkaloids were for the first time obtained by HPCCC separation with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (1:2:1:2, v/v). This process produced 131.3 mg daurisolin, 197.1 mg dauricine, 32.4 mg daurinoline and 14.7 mg dauricicoline with the purity of 97.6%, 96.4%, 97.2% and 98.3%, respectively from 500 mg crude extract of the roots of M. dauricum in a one-step separation. The purities of compounds were determined by high-performance liquid chromatography (HPLC). Their structures were identified by electrospray ionization mass spectrometer (ESI-MS) and nuclear magnetic resonance (NMR). PMID- 20576477 TI - [Casuistry review of patients undergoing surgery for pituitary adenomas in Getafe University Hospital (Spain)]. AB - OBJECTIVE: To perform a casuistry review of patients diagnosed with pituitary adenomas (PA) who underwent surgery performed by the same neurosurgeon after 1995. MATERIAL AND METHODS: A descriptive and retrospective study was performed in 98 patients with PA undergoing surgery from 1995-2008. Tumor size and data on functionality, pathology and postprocedural complications were analyzed. The study was divided into two periods: 1995-2002 (first period) and 2003-2008 (second period). RESULTS: A total of 110 surgical interventions (59 in the first period and 51 in the second) were performed for 49 non-hormone-producing PA and 61 hormone-producing PA. There were 85 macroadenomas and 25 microadenomas. Cure was achieved in 31 patients (36%) with macroadenomas and in 21 patients (84%) with microadenomas (P=0.05).The number of complications was significantly higher in the first period [32 patients (54 %)] than in the second period [16 patients (31.3%)] (P<0.05). Cure was achieved in 28 patients (47.4%) in the first period compared with 31 (52.1%) in the second (P=0.1). The mortality rate was 0.9%. CONCLUSIONS: As described in previous studies, the cure rate was significantly higher for microadenomas than for macroadenomas. There was a significant reduction in the incidence of surgical complications and a trend toward an increase in the percentage of overall healing in the second period of the study. These results are probably related to the neurosurgeon's greater experience and surgical skill. PMID- 20576478 TI - Questions about 'Posterior perilunate carpal dislocation associated with a multifragmentary distal radius fracture'. PMID- 20576479 TI - A new experimental venous super-drained transmidline abdominal skin flap model in pig. PMID- 20576480 TI - Salvage (tertiary) breast reconstruction after implant failure. AB - BACKGROUND: Salvage breast reconstruction is defined as a complete revision of a previous reconstruction in case of unsatisfactory results or failure of primary or secondary breast reconstruction. We have termed this 'tertiary breast reconstruction'. This article presents our experience with tertiary reconstructions, including the indications, method of reconstruction and outcomes. METHODS: A retrospective note review was performed for all patients who underwent breast reconstruction with autologous tissue under one surgeon between 2002 and 2009 at the University Hospital, Ghent. Out of these 688 patients, 54 patients (7.8%) required tertiary surgery with autologous tissue after failure of implant breast reconstruction. RESULTS: The first reconstructive surgery involved 38 unilateral and 16 bilateral cases with a total of 70 operated breasts. A further 11 breasts were reconstructed following risk-reducing mastectomy or at the patient's request for aesthetic reasons. Out of 81 free-flap reconstructions, the deep inferior epigastric artery perforator (DIEAP) flap was the most harvested at 66 (81%). The mean+/-SD operating time was 7.2+/-1.8 h and the mean hospital stay was 7.2+/-1.9 days. One total flap loss (1.2%) occurred. The mean follow-up was 31 months with a range between 3 months and 6 years. During follow up, 30 patients (55.5%) needed secondary procedures to improve the aesthetic outcome. Donor-site corrections were performed in 18 patients (33%). Revisions of the breast flap were performed in 29 patients (53%). CONCLUSIONS: Restoring the breast envelope and footprint, in addition to excision of scar tissue, is the key step in breast reconstruction. Further corrections are required depending on the amount of the initial damage to the breast or subsequent postoperative complications. PMID- 20576481 TI - Implementation and evaluation of relative and absolute quantification in shotgun proteomics with label-free methods. AB - Tandem mass spectrometry allows for fast protein identification in a complex sample. As mass spectrometers get faster, more sensitive and more accurate, methods were devised by many academic research groups and commercial suppliers that allow protein research also in quantitative respect. Since label-free methods are an attractive alternative to labeling approaches for proteomics researchers seeking for accurate quantitative results we evaluated several open source analysis tools in terms of performance on two reference data sets, explicitly generated for this purpose. In this paper we present an implementation, T3PQ (Top 3 Protein Quantification), of the method suggested by Silva and colleagues for LC-MS(E) applications and we demonstrate its applicability to data generated on FT-ICR instruments acquiring in data dependent acquisition (DDA) mode. In order to validate this method and to show its usefulness also for absolute protein quantification, we generated a reference data set of a sample containing four different proteins with known concentrations. Furthermore, we compare three other label-free quantification methods using a complex biological sample spiked with a standard protein in defined concentrations. We evaluate the applicability of these methods and the quality of the results in terms of robustness and dynamic range of the spiked-in protein as well as other proteins also detected in the mixture. We discuss drawbacks of each method individually and consider crucial points for experimental designs. The source code of our implementation is available under the terms of the GNU GPLv3 and can be downloaded from sourceforge (http://fqms.svn.sourceforge.net/svnroot/fqms). A tarball containing the data used for the evaluation is available on the FGCZ web server (http://fgcz data.uzh.ch/public/T3PQ.tgz). PMID- 20576476 TI - Biophysical characterization of DNA binding from single molecule force measurements. AB - Single molecule force spectroscopy is a powerful method that uses the mechanical properties of DNA to explore DNA interactions. Here we describe how DNA stretching experiments quantitatively characterize the DNA binding of small molecules and proteins. Small molecules exhibit diverse DNA binding modes, including binding into the major and minor grooves and intercalation between base pairs of double-stranded DNA (dsDNA). Histones bind and package dsDNA, while other nuclear proteins such as high mobility group proteins bind to the backbone and bend dsDNA. Single-stranded DNA (ssDNA) binding proteins slide along dsDNA to locate and stabilize ssDNA during replication. Other proteins exhibit binding to both dsDNA and ssDNA. Nucleic acid chaperone proteins can switch rapidly between dsDNA and ssDNA binding modes, while DNA polymerases bind both forms of DNA with high affinity at distinct binding sites at the replication fork. Single molecule force measurements quantitatively characterize these DNA binding mechanisms, elucidating small molecule interactions and protein function. PMID- 20576483 TI - The GEnes in Myopia (GEM) study in understanding the aetiology of refractive errors. AB - Refractive errors represent the leading cause of correctable vision impairment and blindness in the world with an estimated 2 billion people affected. Refractive error refers to a group of refractive conditions including hypermetropia, myopia, astigmatism and presbyopia but relatively little is known about their aetiology. In order to explore the potential role of genetic determinants in refractive error the "GEnes in Myopia (GEM) study" was established in 2004. The findings that have resulted from this study have not only provided greater insight into the role of genes and other factors involved in myopia but have also gone some way to uncovering the aetiology of other refractive errors. This review will describe some of the major findings of the GEM study and their relative contribution to the literature, illuminate where the deficiencies are in our understanding of the development of refractive errors and how we will advance this field in the future. PMID- 20576482 TI - Women in Steady Exercise Research (WISER): study design and methods. AB - PURPOSE: Observational studies have shown that physical activity is inversely associated with breast cancer etiology. WISER is a randomized controlled trial examining the effects of exercise training on oxidative stress, and hormonal and metabolic factors associated with breast cancer risk. METHOD: Subjects were recruited via emails, flyers, and mass media advertising. Inclusion criteria included: sedentary, age 18-30 years, non-smokers, BMI 18-40 kg/m2, not using any hormonal contraceptives. After completion of all baseline measures subjects were randomized into a control group or an exercise intervention for 4 menstrual cycles. The exercise group was asked to complete five 45 min exercise sessions per week. Exercise intensity was set at 65-70% of maximum age- predicted heart rate (max HR) and increased every four weeks. All women provided blood samples four times during the study for measurement of blood F2-isoprostanes, hormones and IGF-axis proteins. In addition, 24-hour urine samples were collected at baseline and follow-up for measurement of estrogen metabolites, as well as 24 hour food records to monitor participants' diets. DISCUSSION: WISER consented 683 women among which 391 enrolled and 319 successfully completed the study. The overall dropout rate was 18.4% (n=72) with a higher number of participants dropping from the exercise group (n=46). No differences were found between dropouts and completers with respect to age, body weight, BMI, and demographic characteristics with the exception of degree of education. Findings from this trial will be useful in understanding the physiologic mechanisms by which exercise possibly contributes to decreased breast cancer risk. PMID- 20576484 TI - Retinoid storage in the egg of reptiles and birds. AB - Storage of retinal has been confirmed in eggs from a range of anamniotic vertebrates (teleosts and amphibians) and an ascidian, but the retinoid-storage state in eggs of oviparous amniotic vertebrates (reptiles and birds) has yet to be clarified in detail. We studied four reptilian and five avian species and found that retinal was commonly stored in their egg yolk. Furthermore, retinal was the major retinoid in reptilian eggs, with only low levels of retinol, whereas significant amounts of retinol as well as retinal were stored in avian eggs. In both reptilian and avian eggs, retinal was commonly bound to proteins, which were assumed to be homologous to the proteins that bind retinal in the eggs of anamniotic vertebrates. Despite the common storage state of retinal, retinol would be bound to different proteins. In the reptilian eggs, retinol was found in the yolk-granule fraction, which also contained retinal. However, retinol in avian eggs was found largely in the yolk-plasma fraction, separate from retinal. These results suggest that retinol storage in avian eggs acquired after the divergence of birds from the reptiles, while retinal storage was acquired before the appearance of the vertebrates, and has subsequently been conserved during evolution of oviparous vertebrates. PMID- 20576485 TI - Salinity-dependent expression of a Na+, K+, 2Cl- cotransporter in gills of the brackish medaka Oryzias dancena: a molecular correlate for hyposmoregulatory endurance. AB - This study used the brackish medaka (Oryzias dancena) to characterize Na+, K+, 2Cl- cotransporter (NKCC) expression from the genetic to cellular level in gills. Using RT-PCR to survey tissue distribution of nkcc1a, 1b, and 2, we report that gills of brackish medaka prominently express Odnkcc1a. The full-length cDNA of Odnkcc1a was cloned from gill tissue. In situ hybridization indicates that Odnkcc1a was localized to mitochondrion-rich (MR) cells. Higher mRNA levels of Odnkcc1a were found in gills from seawater (SW) and brackish water (BW) medaka when compared to freshwater (FW) fish. Furthermore, higher amounts of NKCC1a-like protein were detected by the monoclonal antibody in gills of SW and BW medaka compared to FW medaka. Double immunofluorescence staining revealed that NKCC1a like protein colocalizes with Na+, K+-ATPase on the basolateral membrane of MR cells in BW and SW fish. In addition, transfer of brackish medaka from SW to FW revealed that expression of NKCC1a-like protein in gills was retained until 7days, which is a likely mechanism for maintaining hyposmoregulatory endurance. The study illustrates salinity-dependent expression of NKCC1a in branchial MR cells from brackish medaka and suggests a critical role for NKCC1a in hyposmoregulatory endurance of this fish. PMID- 20576486 TI - The C. elegans hyaluronidase: a developmentally significant enzyme with chondroitin-degrading activity at both acidic and neutral pH. AB - Mammalian hyaluronidases degrade hyaluronan and some structurally related glycosaminoglycans. We generated a deletion mutant in the Caenorhabditis elegans orthologue of mammalian hyaluronidase, hya-1. Mutant animals are viable and grossly normal, but exhibit defects in vulval morphogenesis and egg-laying and showed increased staining with alcian blue, consistent with an accumulation of glycosaminoglycan. A hya-1::GFP reporter was expressed in a restricted pattern in somatic tissues of the animal with strongest expression in the intestine, the PLM sensory neurons and the vulva. Total protein extracts from wild-type animals exhibited chondroitin-degrading but not hyaluronan-degrading activity. Chondroitinase activities were observed at both neutral and acidic pH conditions while both neutral and acidic activities were absent in extracts from hya-1 mutant strains. We also evaluated the function of oga-1, which encodes the C. elegans orthologue of MGEA-5, a protein with hyaluronan-degrading activity in vitro. oga-1 is expressed in muscles, vulval cells and the scavenger-like coelomocytes. An oga-1 mutant strain exhibited egg-laying and vulval defects similar to those of hya-1; chondroitinase activity was unaffected in this mutant. PMID- 20576487 TI - Forecasting in vivo oral absorption and food effect of micronized and nanosized aprepitant formulations in humans. AB - This study coupled results from biorelevant dissolution tests with in silico simulation technology to forecast in vivo oral absorption of micronized and nanosized aprepitant formulations in the pre- and post-prandial states. In vitro dissolution tests of the nanosized aprepitant formulation and micronized drug were performed in biorelevant and compendial media. An in silico physiologically based pharmacokinetic (PBPK) model was developed based on STELLA software using dissolution kinetics, standard gastrointestinal (GI) parameters and post absorptive disposition parameters. GI parameters (gastric emptying rate and GI fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the in vivo oral PK data. Predictions of in vivo performance in each prandial state were evaluated using the AUC and C(max) generated from the simulated PK profiles. To predict oral absorption from the extremely fast dissolving nanosized aprepitant formulation, several variations on a previously published model were evaluated. Although models that assumed that the formulation behaved as an oral solution or that adjusted the dissolution kinetics according to the different numbers of particles per gram between micronized and nanosized aprepitant generated profiles similar to the observed in vivo data in the fed state, simulated profiles for the fasted state showed much faster absorption than that observed in the in vivo data. This appeared to result from the assumption of no absorption restrictions in those models. To better predict in vivo performance in both fasted and fed states, a model that adds permeability restrictions to absorption was applied. This model not only simulated the in vivo profiles for aprepitant well in both prandial states, but also predicted the dependency of the pharmacokinetics on the dose and the particle size of aprepitant. In conclusion, a model based on STELLA software combined with dissolution results in biorelevant media successfully forecasts the in vivo performance of both nanosized and micronized formulations of aprepitant in the fed and fasted states. Although dissolution is the primary limitation to the rate of absorption for micronized aprepitant, some permeability restrictions are revealed for the nanosized formulation. The results also indicate that biorelevant dissolution media have strong advantages over compendial media in forecasting the in vivo behavior of aprepitant. PMID- 20576488 TI - Epac activation induces histone deacetylase nuclear export via a Ras-dependent signalling pathway. AB - Epac (Exchange protein directly activated by cAMP) is a sensor for cAMP and represents a novel mechanism for governing cAMP signalling. Epac is a guanine nucleotide exchange factor (GEF) for the Ras family of small GTPases, Rap. Previous studies demonstrated that, in response to a prolonged beta-adrenergic stimulation Epac induced cardiac myocyte hypertrophy. The aim of our study was to further characterize Epac downstream effectors involved in cardiac myocyte growth. Here, we found that Epac led to the activation of the small G protein H Ras in primary neonatal cardiac myocytes. A Rap GTPase activating protein (RapGAP) partially inhibited Epac-induced H-Ras activation. Interestingly, we found that H-Ras activation involved the GEF domain of Epac. However, Epac did not directly induce exchange activity on this small GTPase protein. Instead, the effect of Epac on H-Ras activation was dependent on a signalling cascade involving phospholipase C (PLC)/inositol 1,3,5 triphosphate receptor (IP3R) and an increase intracellular calcium. In addition, we found that Epac activation induced histone deacetylase type 4 (HDAC4) translocation. Whereas HDAC5 alone was unresponsive to Epac, it became responsive to Epac in the presence of HDAC4 in COS cells. Consistent with its effect on HDAC cytoplasmic shuttle, Epac activation also increased the prohypertrophic transcription factor MEF2 in a CaMKII dependent manner in primary cardiac myocytes. Thus, our data show that Epac activates a prohypertrophic signalling pathway which involves PLC, H-Ras, CaMKII and HDAC nuclear export. PMID- 20576489 TI - Interaction of pneumococcal phase variation, host and pressure/gas composition: virulence expression of NanA, HylA, PspA and CbpA in simulated otitis media. AB - Streptococcus pneumoniae, a leading cause of otitis media (OM), adapts to the host environment and undergoes spontaneous intra-strain phase variations in colony morphology. Transparent (T) phase variants are more efficient in colonizing the nasopharynx while the opaque (O) phase variants exhibit greater virulence during systemic infections. We recently demonstrated that T phase variants exhibited a higher growth rate and greater epithelial adherence and destruction than did O phase variants during interactions with human middle ear (ME) epithelial cells. This study was to delineate the underlying molecular mechanisms. Human ME epithelial cells were preconditioned for 24 h under one of the three simulated ME gas/pressure conditions designed to reflect those for 1) normal ME, 2) ME with Eustachian tube obstruction (ETO) and 3) ME with tympanostomy tube (TT) placement; subsequently exposed to a dose (10(7) CFU/ml) of either T or O phase variants of S. pneumoniae (6A), and then incubated for 1h and 3 h. Gene expressions coding for pneumococcal NanA, HylA, PspA, and CbpA virulence factors in inoculum, epithelium-attached and free-floating bacteria were assayed using real-time PCR. Result showed significantly higher basal expression levels for NanA and HylA in T inoculums than in O inoculum. Furthermore, striking differences between the two phase variants were observed in the forms of the inocula, significantly higher expression levels for PspA in T inoculum, but for CbpA in O inoculum. The TT condition enhanced the molecular activities of NanA, HylA, and PspA virulence factors in epithelium-attached T phase variants and fluid-floating O variants, followed by the ETO condition. Our study suggests that the pneumococcal virulence of the phase variations are modulated by the pathological ME environment and host-pathogen interaction during the pathogenesis of OM. PMID- 20576490 TI - Investigation on the morphological protective effect of 5-hydroxymethylfurfural extracted from wine-processed Fructus corni on human L02 hepatocytes. AB - AIM: To determine the mode of action of 5-hydroxymethylfurfural (5-HMF) extracted from wine-processed Fructus corni on hepatoprotective activities, the effects of 5-HMF on H(2)O(2)-induced human L02 hepatocytes injury was examined. MTHODS: Hepatocytes L02 injured by H(2)O(2) was treated by 5-HMF. The morphological changes of the cells were observed under inverted phase-contrast, fluorescence, and transmission electron microscopy and the activities of caspase-9 and caspase 3 were tested by enzyme-linked immunosorbent detector. RESULTS: It revealed that 5-HMF improved the morphology of H(2)O(2)-treated human L02 hepatocytes, and also inhibited the level of caspase-9 and caspase-3 of them. CONCLUSIONS: These results suggested a morphological hepatocyte protective effect and the anti apoptosis mechanism by 5-HMF. PMID- 20576492 TI - The transit of dosage forms through the colon. AB - Colonic transit is a subject of great relevance when considering in vivo/in vitro relationships for oral controlled release dosage forms. Our knowledge of colonic motility has first come from the clinic, where measurement of the whole gut transit of different excreted markers was used as a method of discriminating pathologies. X-ray contrast, although widely available, was used sparing due to the accumulating dosimetry associated with each exposure. Although such methods were used for swallowing studies, gamma scintigraphy allowed physicians to measure colon function with a more moderate radiation burden. The ability to label meal and dosage form separately and to measure dispersion with more certainty, prompted the use in pharmaceutical sciences; finally, the relationship between blood concentrations and transit of different sized dosage began to be understood. This mini-review considers the development of colon transit measurements and how different designs of clinical assessment assist in elucidating size and shape influence on colon transit in man. PMID- 20576491 TI - Convergence of thalamic and cortical pathways in cat auditory cortex. AB - Cat auditory cortex (AC) receives input from many thalamic nuclei and cortical areas. Previous connectional studies often focused on one connectional system in isolation, limiting perspectives on AC computational processes. Here we review the convergent thalamic, commissural, and corticocortical projections to thirteen AC areas in the cat. Each input differs in strength and may thus serve unique roles. We compared the convergent intrinsic and extrinsic input to each area quantitatively. The intrinsic input was almost half the total. Among extrinsic projections, ipsilateral cortical sources contributed 75%, thalamic input contributed 15%, and contralateral sources contributed 10%. The patterns of distribution support the division of AC areas into families of tonotopic, non tonotopic, multisensory, and limbic-related areas, each with convergent input arising primarily from within its group. The connections within these areal families suggest a form of processing in which convergence of input to an area could enable new forms of integration. In contrast, the lateral connections between families could subserve integration between categorical representations, allowing otherwise independent streams to communicate and thereby coordinating operations over wide spatial and functional scales. These patterns of serial and interfamilial cooperation challenge more classical models of organization that underestimate the diversity and complexity of AC connectivity. PMID- 20576494 TI - Predicting safety toleration of pharmaceutical chemical leads: cytotoxicity correlations to exploratory toxicity studies. AB - The selection and application of appropriate safety screening paradigms could revolutionize the drug discovery process by reducing safety-related attrition. While mechanism specific genotoxicity and safety pharmacology assays are routinely used in screening, the overall value of employing nonspecific cytotoxicity assays remains controversial. A retrospective analysis of safety findings from rat exploratory toxicity studies (4-14 days) utilizing compounds that spanned broad therapeutic targets (protease, transport, G-protein-coupled receptors, and kinase inhibitors, cGMP modulators) demonstrated that safety toleration in vivo could be approximated using cytotoxicity values. A composite safety score was calculated for each compound dose based on findings in each of the following categories: systemic toleration (mortality, food consumption, and adverse clinical signs), clinical chemistry/hematology parameters (deviations from normal ranges), and multiorgan pathology (necrosis or incidence/severity of histologic change). Binning compounds into potent (LC(50)<10 microM) and non potent (LC(50)>100 microM) cytotoxicants in vitro showed that compared to non potent cytotoxicants the exposure to potent cytotoxicants in vivo resulted in higher overall severity scores at lower exposures. Correlating overall toleration for individual compounds was further refined when in vivo exposure was considered. When average plasma exposure (Cp(ave)) for a compound exceeded its mean lethal concentration (LC(50)) in vitro (Cp(ave)/LC(50)>1), higher overall severity scores were achieved compared to lower exposure margins (Cp(ave)/LC(50) <0.01). Based on this analysis, the ability to select lead series and individual compounds with better safety characteristics is presented. In summary, cytotoxicity screening can be used to approximate, not define, the safety characteristics of lead pharmaceutical series early in the drug discovery process. PMID- 20576493 TI - Diesel exhaust particles modulate vascular endothelial cell permeability: implication of ZO-1 expression. AB - Exposure to air pollutants increases the incidence of cardiovascular disease. Recent toxicity studies revealed that ultra-fine particles (UFP, d(p)<100-200 nm), the major portion of particulate matter (PM) by numbers in the atmosphere, induced atherosclerosis. In this study, we posited that variations in chemical composition in diesel exhausted particles (DEP) regulated endothelial cell permeability to a different extent. Human aortic endothelial cells (HAEC) were exposed to well-characterized DEP (d(p)<100 nm) emitted from a diesel engine in either idling mode (DEP1) or in urban dynamometer driving schedule (UDDS) (DEP2). Horse Radish Peroxidase-Streptavidin activity assay showed that DEP2 increased endothelial permeability to a greater extent than DEP1 (control=0.077+/-0.005, DEP1=0.175+/-0.003, DEP2=0.265+/-0.006, n=3, p<0.01). DEP2 also down-regulated tight junction protein, Zonular Occludin-1 (ZO-1), to a greater extent compared to DEP1. LDH and caspase-3 activities revealed that DEP-mediated increase in permeability was not due to direct cytotoxicity, and DEP-mediated ZO-1 down regulation was not due to a decrease in ZO-1 mRNA. Hence, our findings suggest that DEP1 vs. DEP2 differentially influenced the extent of endothelial permeability at the post-translational level. This increase in endothelium permeability is implicated in inflammatory cell transmigration into subendothelial layers with relevance to the initiation of atherosclerosis. PMID- 20576495 TI - Evaluation of mitochondrial respiratory chain in the brain of rats after pneumococcal meningitis. AB - The brain is highly dependent on ATP and most cell energy is obtained through oxidative phosphorylation, a process requiring the action of various respiratory enzyme complexes located in a special structure of the inner mitochondrial membrane. Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensory motor deficits, seizures, and impairments of learning and memory. In this context, we evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats submitted to meningitis by S. pneumoniae inoculation into the cisterna magna. Our results demonstrated that complex I activity was not altered in cerebral cortex after meningitis; complexes II, III and IV were increased 24 and 48h after meningitis. We have also verified that complex I was inhibited in prefrontal cortex 48h after meningitis; complexes II, III and IV were not altered. Our results also demonstrated that complex I activity was inhibited in striatum, hippocampus and cerebellum 24h after meningitis. Moreover, complex II activity was increased in hippocampus and striatum 24 and 48h after meningitis; complexes III and IV activity were increased in striatum, hippocampus and cerebellum 48h after meningitis. Taking together previous reports and our present findings, we speculate that oxidative stress and metabolism impairment might contribute, at least in part, for the pathogenesis of pneumococcal meningitis. PMID- 20576496 TI - Laminae-specific distribution of alpha-subunits of voltage-gated sodium channels in the adult rat spinal cord. AB - While the voltage-gated sodium channels (VGSCs) are the key molecules for neuronal activities, the precise distribution of them in spinal cord is not clear in previous studies. We examined the expression of mRNAs for alpha-subunits of VGSC (Navs) in adult rat spinal cord before and 7 days after L5 spinal nerve ligation (SPNL) or complete Freund's adjuvant (CFA)-induced paw inflammation by in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, and immunohistochemistry. Nav1.1 and Nav1.6 mRNAs were present in all laminae, except for lamina II, including the spinothalamic tract neurons in lamina I identified by retrograde tracing of Fluoro-gold. Nav1.2 mRNA was predominantly observed in the superficial layers (laminae I, II), and Nav1.3 mRNA was more restricted to these layers. All these transcripts were expressed by the neurons characterized by immunostaining for neuron-specific nuclear protein. Nav1.7 mRNA was selectively expressed by a half of motoneurons in lamina IX. No signals for Nav1.8 or Nav1.9 mRNAs were detected. Immunohistochemistry for Nav1.1, Nav1.2, Nav1.6, and Nav1.7 proteins verified some of these neuronal distributions. L5 SPNL decreased Nav1.1 and Nav1.6 mRNAs, and increased Nav1.3 and Nav1.7 mRNAs in the axotomized spinal motoneurons, without any changes in other laminae of L4-6 spinal segments. Intradermal injection of CFA did not cause any transcriptional change. Our findings demonstrate that spinal neurons have different compositions of VGSCs according to their location in laminae. Pathophysiological changes of spinal neuronal activity may due to post transcriptional changes of VGSCs. Comparison with our previous data concerning the subpopulation-specific distribution of Nav transcripts in primary afferent neurons provides potentially specific targets for local analgesics at the peripheral nerve and spinal levels. PMID- 20576497 TI - In vivo modulation of the firing activity of putative slow- and fast-spiking interneurons in the medial prefrontal cortex by 5-HT3 receptors in 6 hydroxydopamine-induced Parkinsonian rats. AB - In the present study, we examined changes in the firing rate and firing pattern of putative slow-spiking (SS) and fast-spiking (FS) interneurons in medial prefrontal cortex (mPFC) and the effect of 5-hydroxytryptamine-3 (5-HT(3)) receptor agonist SR 57227A on the neuronal firing in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) by using extracellular recording. The lesion of the SNc in rats decreased the firing rate of FS interneurons and the firing pattern of both SS and FS interneurons changed towards a more burst-firing. Systemic administration of SR 57227A (40-640 microg/kg, i.v.) increased the firing rate of SS interneurons, and decreased FS interneurons in sham-operated and the lesioned rats, respectively. The doses producing excitation or inhibition in the lesioned rats were higher than sham operated rats. The local application of SR 57227A (0.01 microg) in mPFC excited SS interneurons, and inhibited FS interneurons in sham-operated rats, while having no effects on firing rate in the lesioned rats. Systemic administration of GABA(A) receptor antagonist bicuculline (2 mg/kg, i.v.) excited FS interneurons in sham-operated rats, whereas bicuculline did not change the activity of FS interneurons in the lesioned rats. Our findings indicate that the putative SS and FS interneurons activity is modulated through activation of 5-HT(3) receptor by direct or indirect action, and the lesion of the SNc leads to changes in firing activity of the SS and FS interneurons and decreased response of these interneurons to SR 57227A, suggesting dysfunction and/or down-regulation of 5 HT(3) receptor on interneurons in the 6-hydroxydopamine-lesioned rats. PMID- 20576498 TI - Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice. AB - Changes in brain-derived neurotrophic factor (BDNF) expression have been implicated in the etiology of psychiatric disorders. To investigate pathological mechanisms elicited by perturbed BDNF signaling, we examined mutant mice with central depletion of BDNF (BDNF(2L/2LCk-cre)). A severe impairment specific for the serotonin 2A receptor (5-HT(2A)R) in prefrontal cortex was described previously in these mice. This is of much interest, as 5-HT(2A)Rs have been linked to neuropsychiatric disorders and anxiety-related behavior. Here we further characterized the serotonin receptor alterations triggered by BDNF depletion. 5-HT(2A) ([(3)H]-MDL100907) and 5-HT(1A) ([(3)H]-WAY100635) receptor autoradiography revealed site-specific alterations in BDNF mutant mice. They exhibited lower 5-HT(2A) receptor binding in frontal cortex but increased binding in hippocampus. Additionally, 5-HT(1A) receptor binding was decreased in hippocampus of BDNF mutants, but unchanged in frontal cortex. Molecular analysis indicated corresponding changes in 5-HT(2A) and 5-HT(1A) mRNA expression but normal 5-HT(2C) content in these brain regions in BDNF(2L/2LCk-cre) mice. We investigated whether the reduction in frontal 5-HT(2A)R binding was reflected in reduced functional output in two 5-HT(2A)-receptor mediated behavioral tests, the head-twitch response (HTR) and the ear-scratch response (ESR). BDNF(2L/2LCk-cre) mutants treated with the 5-HT(2A) receptor agonist (+/-)-2,5-dimethoxy-4 iodoamphetamine (DOI) showed a clearly diminished ESR but no differences in HTR compared to wildtypes. These findings illustrate the context-dependent effects of deficient BDNF signaling on the 5-HT receptor system and 5-HT(2A)-receptor functional output. PMID- 20576499 TI - AKT/GSK-3beta/beta-catenin signalling within hippocampus and amygdala reflects genetically determined differences in posttraumatic stress disorder like symptoms. AB - Only a small percentage of individuals develop posttraumatic stress disorder (PTSD) in the aftermath of a trauma. It is still largely unknown to what extent gene-environment interactions contribute to the inter-individual differences in PTSD susceptibility and resilience and what cellular processes may underlie long term maintenance of the disorder. Here we employed a mouse model of PTSD to unravel the contribution of genetic background and maternal influences on long lasting changes in kinase and transcription factor activities in PTSD-susceptible C57BL/6NCrl (B6N) and resilient C57BL/6JOlaHsd (B6JOla) mice. Mice received an inescapable foot shock and were tested for activity changes in the AKT/GSK 3beta/beta-catenin-pathway in specific brain structures 42 days later. To control for prenatal and postnatal environmental (i.e. maternal) factors part of the experiments were performed with animals originating from within-strain and between-strain embryo transfers. In PTSD-susceptible B6N mice, long-term maintenance of contextual and sensitized fear was accompanied by (i) increased levels of phosphorylated AKT within the dorsal hippocampus and (ii) higher levels of phosphorylated AKT and GSK-3beta and increased beta-catenin levels within the basolateral amygdala. In animals originating from embryo transfers, levels of phosphorylated GSK-3beta and of beta-catenin were decreased in the dorsal hippocampus, but increased in the basolateral amygdala of shocked B6N mice compared to shocked B6JOla mice. This was independent of the genotype of the recipient mothers. At the behavioural level, these differences coincided with sustained sensitized and more pronounced contextual fear of B6N compared to B6JOla mice. Taken together our study identifies lasting changes in the AKT/GSK 3beta/beta-catenin cascade within the hippocampus and amygdala as molecular correlates of genetically determined differences in the severity of PTSD-like symptoms. PMID- 20576500 TI - Regulatory role of nitric oxide in the reduced survival of erythrocytes in visceral leishmaniasis. AB - BACKGROUND: Nitric oxide (NO) plays a vital role in maintaining the survivability of circulating erythrocytes. Here we have investigated whether NO depletion associated with visceral leishmaniasis (VL) is responsible for the reduced survival of erythrocytes observed during the disease. METHODS: Infected hamsters were treated with standard anti-leishmanial sodium stibogluconate (SAG) and NO donor isosorbide dinitrate (ISD). Erythrophagocytosis by macrophages was determined by labelling the cells with FITC followed by flow cytometry. Aggregation of band3 was estimated from band3 associated EMA fluorescence. Caspase 3 activity was measured using immunosorbent assay kit. Phosphatidylserine (PS) externalization and cell shrinkage were determined using annexin V. Aminophspholipid translocase and scramblase activities were measured following NBD-PS and NBD-PC internalization, respectively. RESULTS: Impairment of both synthesis and uptake of NO resulted in decreased bioavailability of this signaling molecule in erythrocytes in VL. NO level was replenished after simultaneous treatment with ISD and SAG. Combination treatment decreased red cell apoptosis in infected animals by deactivating caspase 3 through s-nitrosylation. Drug treatment prevented infection-mediated ATP depletion and altered calcium homeostasis in erythrocytes. Improved metabolic environment effectively amended dysregulation of aminophospholipid translocase and scramblase, which in turn reduced cell shrinkage, and exposure of phosphatidylserine on the cell surface under the diseased condition. CONCLUSION AND GENERAL SIGNIFICANCE: In this study, we have identified NO depletion to be an important factor in promoting premature hemolysis with the progress of leishmanial infection. The study implicates NO to be a possible target for future drug development towards the promotion of erythrocyte survival in VL. PMID- 20576501 TI - Psychological factors in immunomodulation induced by cancer surgery: a review. AB - The immune system's efficacy in detecting and destroying cancer cells varies considerably throughout the stages of cancer development and its role may be critical particularly during the surgical period. Although surgery causes tumor cells to shed into the blood, immune cells have the capacity to destroy these tumor cells. However, surgery also suppresses cytotoxic capacity. It is particularly during this surgical period that psychological factors can have a significant dampening or strengthening impact on surgery-related immunomodulation response, thus exerting an effect on survival. This review describes the immune changes during the peri-surgical period and the influences psychological factors have on immune function, including the immune effects caused by psychological interventions in cancer patients. We recommend that future studies exploring the role of psychological factors on immune function and survival focus more on their influence during the peri-surgical period. PMID- 20576502 TI - Neurotrophin-3 gene, intelligence, and selective attention deficit in a Korean sample with attention-deficit/hyperactivity disorder. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Neurotrophin-3 (NTF3), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, has been identified as a factor in the development of ADHD. We investigated the relationships between ADHD and NTF3 gene polymorphism. METHODS: We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 151 trios, and compared the intelligence quotient (IQ) and a continuous performance test (CPT) according to the genotype of two single-nucleotide polymorphisms (SNPs) (rs6332 and rs6489630) in the NTF3 gene. RESULTS: In the case-control and family-based analyses, NTF3 was not significantly associated with ADHD. However, in the ADHD probands, the subjects with AA genotype in the rs6332 SNP had significantly higher mean T-scores for commission errors on the CPT than did those with the AG genotypes (p=0.045). The mean IQ of the ADHD probands who had the CC genotype of the rs6489630 SNP were higher compared with those who had the CT or TT genotype (p=0.035). The mean T-score for response time on the CPT was higher in the subjects with TT genotype in the rs6489630 SNP compared to those with the CC or CT genotype, even after adjusting for the effect of IQ (p=0.021). CONCLUSIONS: These results provide preliminary evidence of an association between NTF3 and the intelligence and selective attention deficit in the Korean population. PMID- 20576503 TI - A new ligand for targeted drug delivery to tumor stromal cells. PMID- 20576504 TI - Accumulation of salicylic acid-induced phenolic compounds and raised activities of secondary metabolic and antioxidative enzymes in Salvia miltiorrhiza cell culture. AB - The present work investigated the effects of salicylic acid (SA) on the accumulation of phenolic compounds and the activities of PAL, TAT, SOD, CAT and POD enzymes in the Salvia miltiorrhiza cell culture. When SA is applied to the cell culture, phenolic compounds will increase and PAL, TAT, SOD, CAT, and POD enzymes will become more active. The accumulations of phenolic compounds and the PAL activity were stimulated 8h after the treatment with SA. The TAT activity was stimulated after 48 h. The resulting antioxidative enzymes' activities were greatly improved. SA elicitation on the phenolic acid accumulation was depended upon the application dosage and the time-duration. The suitable SA concentration for eliciting phenolic compound accumulations was 6.25-22.5mg/L. The elicitation effect of SA on phenolic compound accumulations correlated with the PAL activity, but not with the TAT activity. This indicates that PAL may be the key enzyme for the biosynthesis of salvianolic acid B and caffeic acid. The raised PAL activity leads to the improvement of the quantity of phenolic compounds. This could be of particular significance by using plant cell culture systems for biotechnological production of plant secondary metabolites such as salvianolic acid B and caffeic acid. PMID- 20576505 TI - The psychophysiology of blood-injection-injury phobia: looking beyond the diphasic response paradigm. AB - Blood-injection-injury (BII) phobia is an anxiety disorder that may be accompanied by vasovagal fainting during confrontation with the feared stimuli. The underlying pattern of autonomic regulation has been characterized as a diphasic response, with initial increases in heart rate and blood pressure that are typical of a fight-flight response, and subsequent drops in blood pressure and/or heart rate that may precipitate vasovagal fainting. Tensing skeletal muscles of the arms, legs, and trunk (applied tension) has been proposed as a technique to cope with this dysregulation. This review critically examines the empirical basis for the diphasic response and its treatment by applied tension in BII phobia. An alternative perspective on the psychophysiology of BII phobia and vasovagal fainting is offered by focusing on hypocapnia that leads to cerebral blood flow reductions, a perspective supported by research on neurocardiogenic and orthostatically-induced syncope. The evidence may indicate a role for respiration-focused coping techniques in BII phobia. PMID- 20576506 TI - Long-term conservation of HCV RNA at 4 degrees C using a new RNA stabilizing solution. AB - Protecting RNA from degradation, whilst maintaining its biological activity, is essential in molecular biology. However, RNA is very sensitive to degradation by ribonucleases, especially at temperatures above 0 degrees C. The stability of RNA was examined at 4 degrees C and -20 degrees C, in a new stabilizing solution consisting of a low-molarity mixture of chaotropic agents guanidinium and ammonium thiocyanate, a buffer for pH stabilization, phenol, and yeast RNA. Two substrates were tested for storage: RNA in human plasma positive for hepatitis C virus (HCV) and naked RNA (purified from HCV positive human plasma or transcribed in vitro). Stability was followed by viral load estimation, using an in-house competitive RT-PCR assay. Naked RNA purified from human plasma positive for HCV was stable at 4 degrees C for at least 24 months. An RNA standard transcribed in vitro was still viable after 36 months of storage at 4 degrees C. Human plasma dilutions positive for HCV were stable for at least 5 months in this solution when stored at 4 degrees C. It was concluded that the described stabilizing solution ensures long-term stability on naked RNA at 4 degrees C, and ideal for the storage of RNA controls and standards for molecular diagnosis, the solution may be used for preserving clinical samples prior to transport to a clinical laboratory. PMID- 20576508 TI - Microcapillary specifically designed for pressure microinjections of very low volumes. AB - Tracer micronjections are very widely used in brain mapping research. While administration of small quantities/volumes of tracers can easily be achieved through iontophoresis, in the case of pressure injections the volume of the substances injected are much more difficult to control. Instead of using different variables like hydrodynamic conductance, pressure pulses, pressure temperature-dependent protocols to quantify very small volumes in the nanoliter range out of a higher volume, within the confines of the present study a novel microcapillary design is presented. This microcapillary contains exactly the volume of tracer one intends to inject, therefore the danger of flooding large brain areas or the risk of tracer leakage to neighbouring nuclei are completely eliminated, and in the same time this design assures that very small and circumscribed areas can be labeled and their connections mapped, thus making the experiments more specific. In combination with high precision stereotaxic measurements these small volumes of tracers can yield well targeted and very discrete injection sites that make possible the mapping of individual nuclear subdivisions or delicate nuclei in the brain. PMID- 20576507 TI - Bilateral cochlear implantation in the ferret: a novel animal model for behavioral studies. AB - Bilateral cochlear implantation has recently been introduced with the aim of improving both speech perception in background noise and sound localization. Although evidence suggests that binaural perception is possible with two cochlear implants, results in humans are variable. To explore potential contributing factors to these variable outcomes, we have developed a behavioral animal model of bilateral cochlear implantation in a novel species, the ferret. Although ferrets are ideally suited to psychophysical and physiological assessments of binaural hearing, cochlear implantation has not been previously described in this species. This paper describes the techniques of deafening with aminoglycoside administration, surgical implantation of an intracochlear array and chronic intracochlear electrical stimulation with monitoring for electrode integrity and efficacy of stimulation. Experiments have been presented elsewhere to show that the model can be used to study behavioral and electrophysiological measures of binaural hearing in chronically implanted animals. This paper demonstrates that cochlear implantation and chronic intracochlear electrical stimulation are both safe and effective in ferrets, opening up the possibility of using this model to study potential protective effects of bilateral cochlear implantation on the developing central auditory pathway. Since ferrets can be used to assess psychophysical and physiological aspects of hearing along with the structure of the auditory pathway in the same animals, we anticipate that this model will help develop novel neuroprosthetic therapies for use in humans. PMID- 20576510 TI - Boron stabilizes peroxide mediated changes in the structure of heme proteins. AB - Boron is reported in this study to stabilize the structure of heme proteins exposed to peroxides. The oxidized heme protein (15 microM) was treated with H(2)O(2) (10mM) in 1M glycine-NaOH buffer (pH 9.2) at 25 degrees C in absence/presence of boron, and characterized by visible absorption spectroscopy, gel exclusion chromatography, native PAGE, HPLC and DLS. Spectral analysis of exposed heme proteins revealed a decrease in absorbance in the Soret region, which was stabilized by boron. The native PAGE analysis of exposed heme proteins showed high molecular weight products; the band intensity was lesser in presence of boron. Further, elution profile of the exposed heme proteins on Sephadex G-200 column and HPLC revealed more than one peak (aggregate formation) when compared to the respective untreated proteins. DLS, which measures the hydrodynamic radius (R(H)), was used to ascertain whether the peaks correspond to monomer, dimer or aggregate forms. The R(H) of boron pretreated heme proteins was close to R(H) of the respective heme protein. Non-heme protein RNase did not show any change when exposed to peroxide. Taken together, results conclude that boron stabilizes the structure of heme proteins, which might be due to specific sites on heme proteins that can bind to borate ions. PMID- 20576509 TI - Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study. AB - Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) main cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n=215) from the main cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement. PMID- 20576511 TI - Histamine H(3) receptor modulates nociception in a rat model of cholestasis. AB - Cholestasis is associated with changes including analgesia. The histaminergic system regulates pain perception. The involvement of histamine H(3) receptors in modulation of nociception in a model of elevated endogenous opioid tone, cholestasis, was investigated in this study using immepip and thioperamide as selective H(3) receptor agonist and antagonist respectively. Cholestasis was induced by ligation of main bile duct using two ligatures and transsection the duct between them. Cholestatic rats had increased tail-flick latencies (TFLs) compared to non-cholestatics. Administration of immepip (5 and 30mg/kg) and thioperamide (10 and 20mg/kg) to the cholestatic groups significantly increased and decreased TFLs compared to the saline treated cholestatic group. Immepip antinociception in cholestatic animals was attenuated by co-administration of naloxone. Immepip and thioperamide injections into non-cholestatic animals did not alter TFLs. At the doses used here, none of the drugs impaired motor coordination, as revealed by the rotarod test. The present data show that the histamine H(3) receptor system may be involved in the regulation of nociception during cholestasis in rats. PMID- 20576513 TI - Isolation of a Lysinibacillus fusiformis strain with tetrodotoxin-producing ability from puffer fish Fugu obscurus and the characterization of this strain. AB - Six dominant strains were isolated from the livers of the puffer fish Fugu obscurus and were screened for their TTX production-ability. Electrospray ionization-mass spectrometry (ESI-MS) analyses revealed that strain B-1 produced TTX and related substances; mouse bioassay revealed that 23.9 mouse units (MU) of toxins were present in 200ml of broth medium. On the basis of the physiological and biochemical characteristics of this strain and the results of 16S rRNA analysis, strain B-1 was identified as Lysinibacillus fusiformis. PMID- 20576512 TI - Mitochondrial helicases and mitochondrial genome maintenance. AB - Helicases are essential enzymes that utilize the energy of nucleotide hydrolysis to drive unwinding of nucleic acid duplexes. Helicases play roles in all aspects of DNA metabolism including DNA repair, DNA replication and transcription. The subcellular locations and functions of several helicases have been studied in detail; however, the roles of specific helicases in mitochondrial biology remain poorly characterized. This review presents important recent advances in identifying and characterizing mitochondrial helicases, some of which also operate in the nucleus. PMID- 20576514 TI - Plumbagin-induced apoptosis in lymphocytes is mediated through increased reactive oxygen species production, upregulation of Fas, and activation of the caspase cascade. AB - Extracts from plants containing plumbagin (PLB) continue to be used as a treatment of a number of chronic immunologically-based diseases. However, most of these claims are supported only by anecdotal evidence with few scientific reports describing the mechanism of action or the efficacy of plumbagin in the suppression of the immune response. In the current study, we tested the hypothesis that plumbagin-induced suppression of the immune response was mediated through the induction of apoptosis. Splenocytes from C57BL/6 mice cultured in the presence of 0.5 microM or greater concentrations of PLB significantly reduced proliferative responses to mitogens, including anti-CD3 mAbs, concanavalin A (Con A), lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) in vitro. Exposure of naive and activated splenocytes to PLB led to a significant increase in the levels of apoptosis. In addition, PLB treatment led to a significant increase in the levels of reactive oxygen species (ROS) in naive and activated splenocytes. Furthermore, treatment with the ROS scavenger, N-acetylcysteine (NAC), prevented PLB-induced apoptosis, suggesting a role of ROS in PLB-induced apoptosis. PLB-induced apoptosis led to ROS-mediated activation of both the extrinsic and intrinsic apoptotic pathways. In addition, plumbagin led to increased expression of Fas. Finally, treatment of mice with PLB (5mg/kg) led to thymic and splenic atrophy as well as a significant suppression of the response to SEB and dinitrofluorobenzene (DNFB) in vivo. Together, these results suggest that plumbagin has significant immunosuppressive properties which are mediated by generation of ROS, upregulation of Fas, and the induction of apoptosis. PMID- 20576516 TI - The backward bifurcation in compartmental models for West Nile virus. AB - In all of the West Nile virus (WNV) compartmental models in the literature, the basic reproduction number serves as a crucial control threshold for the eradication of the virus. However, our study suggests that backward bifurcation is a common property shared by the available compartmental models with a logistic type of growth for the population of host birds. There exists a subthreshold condition for the outbreak of the virus due to the existence of backward bifurcation. In this paper, we first review and give a comparison study of the four available compartmental models for the virus, and focus on the analysis of the model proposed by Cruz-Pacheco et al. to explore the backward bifurcation in the model. Our comparison study suggests that the mosquito population dynamics itself cannot explain the occurrence of the backward bifurcation, it is the higher mortality rate of the avian host due to the infection that determines the existence of backward bifurcation. PMID- 20576515 TI - Comparing three novel endpoints for developmental osteotoxicity in the embryonic stem cell test. AB - Birth defects belong to the most serious side effects of pharmaceutical compounds or environmental chemicals. In vivo, teratogens most often affect the normal development of bones, causing growth retardation, limb defects or craniofacial malformations. The embryonic stem cell test (EST) is one of the most promising models that allow the in vitro prediction of embryotoxicity, with one of its endpoints being bone tissue development. The present study was designed to describe three novel inexpensive endpoints to assess developmental osteotoxicity using the model compounds penicillin G (non-teratogenic), 5-fluorouracil (strong teratogen) and all-trans retinoic acid (bone teratogen). These three endpoints were: quantification of matrix incorporated calcium by (1) morphometric analysis and (2) measurement of calcium levels as well as (3) activity of alkaline phosphatase, an enzyme involved in matrix calcification. To evaluate our data, we have compared the concentration curves and resulting ID(50)s of the new endpoints with mRNA expression for osteocalcin. Osteocalcin is an exclusive marker found only in mineralized tissues, is regulated upon compound treatment and reliably predicts the potential of a chemical entity acting as a bone teratogen. By comparing the new endpoints to quantitative expression of osteocalcin, which we previously identified as suitable to detect developmental osteotoxicity, we were ultimately able to illustrate IMAGE analysis and Ca(2+) deposition assays as two reliable novel endpoints for the EST. This is of particular importance for routine industrial assessment of novel compounds as these two new endpoints may substitute previously used molecular read-out methods, which are often costly and time-consuming. PMID- 20576517 TI - Multiple vitellogenins from the Haemaphysalis longicornis tick are crucial for ovarian development. AB - Ovarian development and egg maturation are crucial processes for the success of reproduction in ticks. Three full-length cDNAs encoding the precursor of major yolk protein, vitellogenin, were obtained from cDNA libraries of the Haemaphysalis longicornis tick and designated as HlVg-1, HlVg-2 and HlVg-3. The HlVg mRNAs were found in fed females with major expression sites in the midgut, fat body and ovary. Native PAGE and Western blot demonstrated that HlVgs in the hemolymph, fat body and ovary of fed females consisted of four major polypeptides. RNAi results showed that HlVg dsRNA-injected ticks obtained lower body weight, egg weight and showed higher mortality of engorged females after blood sucking than control groups. Our results indicate that all HlVgs are essential for egg development and oviposition. PMID- 20576518 TI - Modulation of hypothalamic PTP1B in the TNF-alpha-induced insulin and leptin resistance. AB - We have associated functional and molecular studies of insulin and leptin to investigate the effect of TNF-alpha on central insulin and leptin signaling in rats pre-treated with PTP1B-ASO. The icv infusion of TNF-alpha-induced an increase in PTP1B protein expression and activity, and attenuated insulin and leptin sensitivity and signaling in the hypothalamus. However, TNF-alpha was able to completely blunt the leptin and insulin effect in rats treated with PTP1B-ASO, suggesting that TNF-alpha does not require PTP1B to fully attenuate the leptin and insulin effects. In addition, our data also show that other mechanisms of insulin and leptin resistance are activated in the hypothalamus by TNF-alpha. PMID- 20576519 TI - Glutamate synthase, but not GABA shunt enzymes, contributes to nitrogen metabolism of the sheep abomasal nematode parasites Haemonchus contortus and Teladorsagia circumcincta. AB - Glutamate synthase (E.C. 1.4.1.14) (GOGAT) activity was not detectable in L3 Haemonchus contortus, but was present in L3 Teladorsagia circumcincta and adult worms of both species. GOGAT activity was inhibited by 80% by azaserine. Activity (nmol min(-1) mg(-1) protein) was 33-59 in adult H. contortus, 51-91 in adult T. circumcincta and 24-41 in L3 T. circumcincta, probably depending on exposure to ammonia, as incubation with 1mM NH(4)Cl doubled GOGAT activity. The pH optimum was 7.5 in both species. Either NAD or NADP acted as co-factor. The mean apparent K(m) for 2-oxoglutarate was 0.7 (0.5-0.9) mM and for glutamine was 1.0 (0.5-1.7) mM for different homogenates. There was no detectable activity in whole parasite homogenates of glutamate decarboxylase (E.C. 4.1.1.15) or succinic semialdehyde dehydrogenase (E.C. 1.2.1.24), the first and third enzymes of the GABA shunt, respectively, suggesting that the GABA shunt is not important in general metabolism in these species. PMID- 20576520 TI - SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo. AB - SNAIL, a potent repressor of E-cadherin expression, plays a key role in inducing epithelial-to-mesenchymal transition (EMT) in epithelial cells. During EMT, epithelial cells lose cell polarity and adhesion, and undergo drastic morphological changes acquiring highly migratory abilities. Although there is increasing evidence that EMT is involved in the progression of some human cancers, its significance in the progression of pancreatic cancer remains elusive. In Panc-1, a well-known human pancreatic cancer cell line in which EMT is triggered by TGF-beta1 treatment, SNAIL and vimentin are highly expressed, whereas E-cadherin expression is scant. In contrast, another human pancreatic cancer cell line, BxPC3, in which SNAIL expression is not detected, has high levels of E-cadherin expression and does not undergo EMT upon TGF-beta1 treatment. After transfecting the SNAIL gene into BxPC3, however, the cells undergo EMT with remarkable alterations in cell morphology and molecular expression patterns without the addition of any growth factors. Furthermore, in an orthotopic transplantation model using SCID mice, SNAIL-transfected BxPC3 displayed highly metastatic and invasive activities. In the immunohistochemical analysis of the tumor derived from the SNAIL-expressing BxPC3, alterations suggestive of EMT were observed in the invasive tumor front. SNAIL enabled BxPC3 to undergo EMT, endowing it with a highly malignant potential in vivo. These results indicate that SNAIL-mediated EMT may be relevant in the progression of pancreatic cancer, and SNAIL could be a molecular target for a pancreatic cancer intervention. PMID- 20576521 TI - Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer. AB - BACKGROUND: Glutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer. METHODS: We first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs. RESULTS: Among five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR=0.70, P=0.037), intronic SNP 3828599 (OR=0.68, P=0.025), and 3' UTR SNP rs2070593 (OR=0.48, P=0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D'=0.91). CONCLUSIONS: The reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P=0.004), whereas the 3'UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk. PMID- 20576522 TI - Allele specific Taqman-based real-time PCR assay to quantify circulating BRAFV600E mutated DNA in plasma of melanoma patients. AB - BACKGROUND: BRAF is the most frequently mutated oncogene in melanoma with BRAF(V600E) mutation accounting for 92% of all BRAF variants. As this event occurs early in melanoma progression, the quantification of BRAF-mutated alleles in plasma may represent a useful biomarker for noninvasive diagnosis and prediction of response to therapy. METHODS: We propose an assay based on the use of a locked nucleic acid probe and an allele specific primer to measure plasma circulating BRAF(V600E) concentration in patients affected by cutaneous melanoma (n=55) and non-melanoma skin cancers (n=13) as well as 18 healthy subjects. The assay is highly sensitive and accurate in detecting down to 0.3% of mutated allele in plasma. RESULTS: A significant difference between the control group and invasive melanomas (p<0.01) was evidenced in BRAF(V600E) concentration, either as relative percentage or absolute values. ROC curve indicated that BRAF(V600E) absolute concentration has the maximal diagnostic relevance with 97% sensitivity and 83% specificity. Comparison of the results obtained in plasma with those found in the corresponding tissues indicated an 80% concordance. CONCLUSIONS: The allele specific Taqman-based real-time PCR assay allows the sensitive, accurate and reliable measurement of BRAF(V600E) mutated DNA in plasma. PMID- 20576523 TI - Proteomic analysis of the transitional endoplasmic reticulum in hepatocellular carcinoma: an organelle perspective on cancer. AB - The transitional endoplasmic reticulum (tER) is composed of both rough and smooth ER membranes and thus participates in functions attributed to both these two subcellular compartments. In this paper we have compared the protein composition of tER isolated from dissected liver tumor nodules of aflatoxin B1-treated rats with that of tER from control liver. Tandem mass spectrometry (MS), peptide counts and immunoblot validation were used to identify and determine the relative expression level of proteins. Inhibitors of apoptosis (i.e. PGRMC1, tripeptidyl peptidase II), proteins involved in ribosome biogenesis (i.e. nucleophosmin, nucleolin), proteins involved in translation (i.e. eEF-2, and subunits of eIF-3), proteins involved in ubiquitin metabolism (i.e. proteasome subunits, USP10) and proteins involved in membrane traffic (i.e. SEC13-like 1, SEC23B, dynactin 1) were found overexpressed in tumor tER. Transcription factors (i.e. Pur-beta, BTF3) and molecular targets for C-Myc and NF-kappa B were observed overexpressed in tER from tumor nodules. Down-regulated proteins included cytochrome P450 proteins and enzymes involved in fatty acid metabolism and in steroid metabolism. Unexpectedly expression of the protein folding machinery (i.e. calreticulin) and proteins of the MHC class I peptide-loading complex did not change. Proteins of unknown function were detected in association with the tER and the novel proteins showing differential expression are potential new tumor markers. In many cases differential expression of proteins in tumor tER was comparable to that of corresponding genes reported in the Oncomine human database. Thus the molecular profile of tumor tER is different and this may confer survival advantage to tumor cells in cancer. PMID- 20576524 TI - Cytochrome P450- and peroxidase-mediated oxidation of anticancer alkaloid ellipticine dictates its anti-tumor efficiency. AB - An antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological efficiency is dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation in target tissues. The aim of this review was to summarize our knowledge on the molecular mechanisms of ellipticine action in the cancer cells. The CYP-mediated ellipticine metabolites 9-hydroxy- and 7-hydroxyellipticine and the product of ellipticine oxidation by peroxidases, the ellipticine dimer, are the detoxication metabolites of this compound. In contrast, two carbenium ions, ellipticine-13-ylium and ellipticine-12-ylium, derived from two activation ellipticine metabolites, 13-hydroxyellipticine and 12-hydroxyellipticine, generate two major deoxyguanosine adducts in DNA found in the human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR 32, UKF-NB-3, and UKF-NB-4 cells and glioblastoma U87MG cells in vitro and in rat breast carcinoma in vivo. Formation of these covalent DNA adducts by ellipticine is the predominant mechanism of its cytotoxicity and anti-tumor activity to these cancer cell lines. Ellipticine is also an inducer of CYP1A, 1B1, and 3A4 enzymes in the cancer cells and/or in vivo in rats exposed to this compound, thus modulating its own pharmacological efficiencies. The study forms the basis to further predict the susceptibility of human cancers to ellipticine and suggests that this alkaloid for treatment in combination with CYP and/or peroxidase gene transfer increasing the anticancer potential of this prodrug. It also suggests ellipticine reactive metabolites 13-hydroxyellipticine and 12-hydroxyellipticine to be good candidates for targeting to tumors absent from the CYP and peroxidase activation enzymes. PMID- 20576525 TI - Delusional parasitosis in a patient with brain atrophy and renal failure treated with aripiprazole: case report. PMID- 20576526 TI - Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes. AB - In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre adipocytes, LPA instead induced Erk1/2 activation via two distinct non transactivational pathways, one G(i)-protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation. PMID- 20576527 TI - Pungency of TRPV1 agonists is directly correlated with kinetics of receptor activation and lipophilicity. AB - TRPV1 (transient receptor potential vanilloid 1) is a ligand-gated ion channel expressed predominantly in nociceptive primary afferents that plays a key role in pain processing. In vivo activation of TRPV1 receptors by natural agonists like capsaicin is associated with a sharp and burning pain, frequently described as pungency. To elucidate the mechanisms underlying pungency we investigated a series of TRPV1 agonists that included both pungent and non-pungent compounds covering a large range of potencies. Pungency of capsaicin, piperine, arvanil, olvanil, RTX (resiniferatoxin) and SDZ-249665 was evaluated in vivo, by determining the increase in the number of eye wipes caused by direct instillation of agonist solutions into the eye. Agonist-induced calcium fluxes were recorded using the FLIPR technique in a recombinant, TRPV1-expressing cell line. Current clamp recordings were performed in rat DRG (dorsal root ganglia) neurons in order to assess the consequences of TRPV1 activation on neuronal excitability. Using the eye wipe assay the following rank of pungency was obtained: capsaicin>piperine>RTX>arvanil>olvanil>SDZ-249665. We found a strong correlation between kinetics of calcium flux, pungency and lipophilicity of TRPV1 agonists. Current-clamp recordings confirmed that the rate of receptor activation translates in the ability of agonists to generate action potentials in sensory neurons. We have demonstrated that the lipophilicity of the compounds is directly related to the kinetics of TRPV1 activation and that the latter influences their ability to trigger action potentials in sensory neurons and, ultimately, pungency. PMID- 20576528 TI - Mechanism of inhibition by hydrogen sulfide of native and recombinant BKCa channels. AB - Recent evidence suggests that H(2)S contributes to activation of the carotid body by hypoxia by inhibiting K(+) channels. Here, we determine both the molecular identity of the K(+) channel target within the carotid body and the biophysical characteristics of the H(2)S-evoked inhibition by analyzing native rat and human recombinant BK(Ca) channel activity in voltage-clamped, inside-out membrane patches. Rat glomus cells express the enzymes necessary for the endogenous generation of H(2)S, cystathionine-beta-synthase and cystathionine-gamma-lyase. H(2)S inhibits native carotid body and human recombinant BK(Ca) channels with IC(50) values of around 275 microM. Inhibition by H(2)S is rapid and reversible, works by a mechanism which is distinct from that suggested for CO gas regulation of this channel and does not involve an interaction with either the "Ca bowl" or residues distal to this Ca(2+)-sensing domain. These data show that BK(Ca) is a K(+) channel target of H(2)S, and suggest a mechanism to explain the H(2)S dependent component of O(2) sensing in the carotid body. PMID- 20576529 TI - Purification and characterization of Stn1p, a single-stranded telomeric DNA binding protein. AB - In Saccharomyces cerevisiae, Stn1p and Ten1p are required for telomere maintenance. These two proteins and another telomeric single-stranded DNA binding protein, Cdc13p, have been proposed to form a complex to control telomere integrity. In this work, we purified the recombinant Stn1p in Escherichia coli and found that the purified protein could specifically interact with single stranded telomeric DNA in vitro. Co-fractionation of co-overexpressed Stn1p and Ten1p in insect cells revealed their stable association. A Stn1p/Ten1p binary complex was reconstituted with purified recombinant proteins in vitro. These results indicated that Stn1p and Ten1p interact with each other directly, which is important in telomere length regulation and end protection. PMID- 20576530 TI - Efficient production of human Fas receptor extracellular domain-human IgG1 heavy chain Fc domain fusion protein using baculovirus/silkworm expression system. AB - The fusion protein consisting of human Fas receptor extracellular domain and human IgG1 heavy chain Fc domain (hFasRECD-Fc) is a medically important protein that potentially has therapeutic uses. The fusion gene composed of a synthetic human Fas receptor extracellular domain gene and the cDNA encoding human IgG1 heavy chain Fc domain was investigated on the secretory expression using two baculovirus systems which employed either Spodoptera frugiperda 9 (Sf9) cell line or Bombyx mori (silkworm) larvae as the host organism. Both expression systems produced the functional hFasRECD-Fc as a dimer molecule linked by disulfide bridges. The secretion level per unit volume was much higher in the case of silkworm larvae as compared to Sf9 cell line, and was estimated to be more than 150 times. A substantially pure hFasRECD-Fc sample from silkworm larvae was obtained by single step Protein G-agarose affinity column chromatography. The affinity purified sample was further fractionated by anion-exchange chromatography with the final purification yield of 22.5 mg from 26 ml hemolymph. The hFasRECD-Fc from silkworm larvae and the tag-free human Fas ligand extracellular domain derivative from Pichia pastoris formed a stable complex in solution, which was verified by size-exclusion chromatography. This study demonstrated that the baculovirus/silkworm expression system provided the means for efficient production of highly pure hFasRECD-Fc with functional activity. PMID- 20576531 TI - Disruption of Pdia3 gene results in bone abnormality and affects 1alpha,25 dihydroxy-vitamin D3-induced rapid activation of PKC. AB - 1,25-dihydroxy-vitamin D3 [1alpha,25(OH)2D3] is a critical regulator of bone development. Protein disulfide isomerase A3 (Pdia3) is a multifunctional protein that has been associated with rapid membrane-initiated signalling by 1alpha,25(OH)2D3 in several cell types. To identify the physiological roles of Pdia3 in skeletal development, we generated Pdia3-deficient mice. No homozygous mice were observed at birth, indicating that the targeted disruption of the Pdia3 gene resulted in embryonic lethality. Pdia3 deficiency also resulted in skeletal manifestations as revealed by muCT analysis of femurs from 15-week-old heterozygous mice. The Pdia3+/- mice had increased metaphyseal bone volume and trabeculae compared to Pdia3+/+ mice. In contrast, the area and thickness of cortical bone at the femoral mid-diaphysis of Pdia3+/+ mice significantly exceeded that of Pdia3+/- mice. In vitro studies in osteoblast-like MC3T3-E1 cells showed that silencing of Pdia3 abolished 1alpha,25(OH)2D3-induced rapid activation of protein kinase C (PKC) while overexpression of Pdia3 resulted in augmentation of PKC activity by 1alpha,25(OH)2D3. Taken together, these data indicated that Pdia3 plays a crucial role in 1alpha,25(OH)2D3-regulated bone formation and the Pdia3-PKC signalling pathway might be involved in this process. PMID- 20576532 TI - Early pregnancy blood lead levels and the risk of premature rupture of the membranes. AB - To clarify the effects of lead on fetal premature rupture of the membranes (PROM), blood lead concentrations were measured using inductively coupled plasma mass spectrometry in 332 women, aged 16-35 years, during their early pregnancy period (8-12 weeks). Blood lead concentrations were significantly higher in the 36 PROM deliveries than in the 296 non-PROM deliveries (mean +/- SD, 4.61 +/- 2.37 and 3.69 +/- 1.85 MUg/dl, respectively; p<0.05). The logistic regression analysis revealed that a 1-unit increase in the logarithm of the blood lead level led to a several-fold increase in the risk of PROM (unit risk=17.98, 95% CI 1.6 198.6). Thus, it is suggested that lead can increase the risk of PROM in pregnant women with mean blood lead less than 5 MUg/dl. PMID- 20576534 TI - PROKR2 is associated with methamphetamine dependence in the Japanese population. AB - BACKGROUND: Many patients with drug addiction are reported to have comorbid mood disorders. One of the suggested pathophysiological mechanisms for mood disorders is disruption of circadian rhythms. Several animal studies have shown that methamphetamine altered the expression of circadian clock molecules in the brain. Therefore, it is possible that mood disorders and drug addiction have common susceptibility genes. Recently, we reported that the prokineticin 2 receptor gene (PROKR2) was associated with mood disorders including major depressive disorder and bipolar disorder in the Japanese population. In the present study, therefore, we conducted an association analysis of tagging SNPs in PROKR2 with Japanese methamphetamine dependence patients. METHODS: Using five tagging SNPs in PROKR2, we conducted a genetic association analysis of case-control samples (199 methamphetamine dependence patients and 337 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. RESULTS: We detected a significant association between PROKR2 and methamphetamine dependence patients in allele/genotype-wise and haplotype-wise analysis. CONCLUSION: Our results suggest that PROKR2 may play a role in the pathophysiology of methamphetamine dependence in the Japanese population. However, because we did not perform a mutation scan of PROKR2, a replication study using a larger sample may be required for conclusive results. PMID- 20576535 TI - Clinical and economic burden of pneumococcal disease in older US adults. AB - We developed a model characterizing rates and costs of pneumococcal disease in the US to estimate the expected annual clinical and economic burden of this condition among older adults. Among the 91.5 million US adults aged >or=50 years, 29,500 cases of invasive pneumococcal disease, 502,600 cases of nonbacteremic pneumococcal pneumonia, and 25,400 pneumococcal-related deaths are estimated to occur yearly; annual direct and indirect costs are estimated to total $3.7 billion and $1.8 billion, respectively. Pneumococcal disease remains a substantial burden among older US adults, despite increased coverage with PPV23 and indirect benefits afforded by PCV7 vaccination of young children. PMID- 20576536 TI - High costs of influenza: Direct medical costs of influenza disease in young children. AB - This study determined direct medical costs for influenza-associated hospitalizations and emergency department (ED) visits. For 3 influenza seasons, children <5 years of age with laboratory-confirmed influenza were identified through population-based surveillance. The mean direct cost per hospitalized child was $5402, with annual cost burden estimated at $44 to $163 million. Factors associated with high-cost hospitalizations included intensive care unit (ICU) admission and having an underlying high-risk condition. The mean medical cost per ED visit was $512, with annual ED cost burden estimated at $62 to $279 million. Implementation of the current vaccination policies will likely reduce the cost burden. PMID- 20576537 TI - Structure-function relationship of king cobra cathelicidin. AB - King cobra cathelicidin (OH-CATH) is composed of 34 amino acid residues having strong antibacterial and very weak hemolytic activities as reported by us recently. OH-CATH can be served as a valuable template to develop novel therapeutic drugs. In this study, OH-CATH and six of its analogs were synthesized to explore their structure-function relationships based on their bactericidal and hemolytic activities. Experimental results of OH-CATH(3-34) and OH-CATH(5-34) indicated that the N-terminal 4 amino acid residues of OH-CATH played an important role on its hemolytic activity but had weak effects on its bactericidal activity. Among OH-CATH and its analogs, OH-CATH(5-34) had the lowest hemolytic activity while maintained strong antimicrobial activity. To evaluate its potential usage, the biological activities of OH-CATH(5-34) were compared with those of pexiganan. The bactericidal activity of OH-CATH(5-34) against 5 different species (11 laboratory strains) was 2-4 times stronger than that of pexiganan (4-16 microg/ml vs 8-32 microg/ml). Hemolytic activity of OH-CATH(5-34) against human erythrocytes was 0.69% while that of pexiganan was 16.5% at the dosage of 200 microg/ml. OH-CATH(5-34) showed very weak cytotoxic activities against primary rabbit ventricular endothelial cells and four human cancer cell lines whereas pexiganan showed strong cytotoxic activity against these five cell lines (IC(50)=20-90 microg/ml). The intravenous LD(50) value of OH-CATH(5-34) on mice was 7-fold higher than that of pexiganan (175 mg/kg vs 25mg/kg). Taken together, our results suggested that OH-CATH(5-34) should be considered as an excellent candidate for developing therapeutic drugs. PMID- 20576538 TI - Open reading frame 60 of the Bombyx mori nucleopolyhedrovirus plays a role in budded virus production. AB - Open reading frame 60 (bm60) of the Bombyx mori nucleopolyhedrovirus (BmNPV) is a conserved gene among group I and some group II NPVs. bm60 encodes a late expressed protein that localizes to both the cytoplasm and nucleus of infected cells. This paper describes the characterization of a BmNPV mutant (vbm60-Null) lacking functional bm60. It was observed that the production of budded virus (BV) was reduced by nearly an order of magnitude relative to wt virus in vbm60-Null infected BmN cells and B. mori larvae. Quantitative real-time PCR assay showed that the viral DNA replication was affected in infected cells due to disruption of bm60. Larval bioassays showed that the speed of kill of vbm60-Null virus was greatly reduced, as it took approximately 28-36 h longer to kill the fifth instar B. mori larvae. These results suggest that BmNPV bm60 is not essential for viral replication, but required for efficient BV production. PMID- 20576539 TI - Lateralized response of oxytocinase activity in the medial prefrontal cortex of a unilateral rat model of Parkinson's disease. AB - Individuals in the early stage of Parkinson's disease exhibit cognitive impairments as a result of hemisphere damage. The mesocortical dopamine system, particularly the medial prefrontal cortex (mPFC), is implicated in cognitive functions and is characterized by an asymmetric organization. Oxytocinase activity (OX) is also asymmetrically distributed in the mPFC of normal rats and is involved in cognitive functions. OX was measured in the left and right mPFC of rats with left or right hemi-parkinsonism, induced by intrastriatal injections of 6-hydroxydopamine, and compared with sham controls. These results demonstrated that the striking basal left predominance of OX observed in both the left and the right sham controls was radically disrupted in lesioned animals. The bilateral distribution in lesioned animals was altered differently depending on the injured hemisphere. These results may reflect changes in the enzyme substrates and consequently in the functions in which they are involved. These results may account, in part, for the cognitive abnormalities observed in hemi-parkinsonism. PMID- 20576540 TI - Opinions on tobacco control policies in Lausanne, Switzerland, 2003-2006. AB - OBJECTIVE: To assess the determinants of opinions regarding tobacco control policies in the Swiss general population. METHODS: Cross-sectional study conducted between 2003 and 2006 on a random sample of adult residents of Lausanne, Switzerland, aged 35-75 years (2601 women and 2398 men). Nine questions on smoking policies were applied. RESULTS: Ninety-five percent of responders supported policies that would help smokers to quit, 92% no selling of tobacco to subjects aged less than 16 years, 87% a smoking ban in public places and 86% a national campaign against smoking. A further 77% supported a total ban on tobacco advertising, 74% the reimbursement of nicotine replacement therapies and 70% an increase in the price of cigarettes. A lower support was found for two non evidence-based interventions total ban of tobacco sales (35%) and promotion of light cigarettes (22%). Never smokers, women, physically active subjects, teetotallers and subjects with lower educational level were more likely to favour stronger measures while no differences were found between age groups. Reimbursement of nicotine replacement therapies was favoured more by current smokers and inactive subjects. CONCLUSION: The vast majority of responders supported the recommended tobacco control policies. Opinions regarding specific interventions vary according to the policy and subjects' characteristics. PMID- 20576541 TI - Xclaudin 1 is required for the proper gastrulation in Xenopus laevis. AB - Claudin 1 is one of the tight junctional proteins involved in the tight sealing of the cellular sheets and plays a crucial role in the maintenance of cell polarity. Although its structure and physiological function in intercellular adhesion is relatively well understood, we have little information about its possible involvement in early development of vertebrates. We found Xclaudin 1 is expressed maternally in the oocyte of Xenopus laevis and the zygotic expression initiates stage 9 in the animal hemisphere but not in the vegetal hemisphere, limited on the ectoderm and mesoderm until the end of gastrulation. We have investigated a potential role for claudin 1 at gastrulation by gain and loss-of function studies. Over-expression of Xclaudin 1 resulted in gastrulation defect in a dose-dependent manner. Knockdown of Xclaudin 1 by antisense morpholino oligonucleotides (MOs) blocked convergent extension, whereas ectopic expression of Xclaudin 1-myc mRNA rescued these defects. However, altered expression of Xclaudin 1 did not inhibit mesodermal gene expression. Taken together, our results suggest that Xclaudin 1 is required for proper convergent extension movement during Xenopus gastrulation. PMID- 20576542 TI - Safety of assessment of patients with potential ischemic chest pain in an emergency department waiting room: a prospective comparative cohort study. AB - STUDY OBJECTIVE: Emergency department (ED) crowding has been associated with a variety of adverse outcomes. Current guidelines suggest that patients with potentially ischemic chest pain should undergo rapid assessment and treatment in a monitored setting to optimize the diagnosis of acute coronary syndrome. These patients may be at high risk of incorrect diagnosis and adverse events when their evaluation is delayed because of crowding. To mitigate crowding-related delays, we developed processes that enabled emergency physicians to evaluate potentially sick patients in the waiting room when all nurse-staffed stretchers are occupied. The objective of this study was to investigate the safety of waiting room chest pain evaluation. METHODS: This prospective comparative cohort study was conducted in a busy urban, tertiary care ED. Explicit triage and waiting room evaluation processes were introduced. One thousand one hundred seven patients with chest pain of potential cardiac origin were triaged either to a monitored bed or a waiting room chair, depending on bed availability and triage judgment. After diagnostic evaluation, patients were followed for 30 days to identify the proportion of missed cases of acute coronary syndrome (primary outcome) and other prespecified adverse events. Analysis was based on intention to treat. RESULTS: Eight hundred four patients were triaged to monitored bed and 303 to waiting room evaluation. Initial vital signs were similar, but the waiting room group was younger and had lower rates of some cardiovascular risk factors. The rate of acute coronary syndrome, defined as acute myocardial infarction or objective unstable angina, was 11.7% in the monitored bed group and 7.6% in waiting room patients. There were no missed acute coronary syndrome cases in either the monitored bed group (0%; 95% confidence interval [CI] 0% to 0.4%) or the waiting room group (0%; 95% CI 0% to 1.0%). There were 32 adverse events in the monitored bed group (4.0%; 95% CI 2.6% to 5.3%) and 2 in the waiting room group (0.7%; 95% CI 0% to 1.6%). CONCLUSION: Our organized approach to triage and waiting room evaluation for stable chest pain patients was safe and efficient. Although waiting room evaluation is not ideal, it may be a feasible contingency strategy for periods when ED crowding compromises access to monitored, nurse-staffed ED beds. PMID- 20576544 TI - [Reflexions on conflicts of interest]. PMID- 20576543 TI - Proposal for a revised reference concentration (RfC) for mercury vapour in adults. AB - Worldwide, approximately 30-50 millions of people are living in small scale gold mining areas and are primarily burdened by mercury vapour. In the frame of our study, 306 mercury (Hg) vapour burdened adults, working and/ or living in two small scale gold mining areas in Zimbabwe and Tanzania and 58 volunteers from near-by unburdened communities were medically investigated. In addition, blood, urine and hair samples from each participant were analyzed for mercury. Altogether, 26 anamnestic and 24 clinical signs and symptoms, which may be caused by Hg vapour, were evaluated. Multivariate analysis was performed to investigate the influence of the mercury concentration in the bio-monitors on the evaluated anamnestic and clinical signs and symptoms taking into account age, gender, health status, alcohol consumption, use of pesticides and gasoline sniffing. Out of the resulting correlations between concentration and effect, ROC-curves were calculated to determine best estimates of the cut-off-values in the bio monitors. For the parameters ataxia of gait and sadness cut-off-values of 4.7 and 3.6 microg Hg/g crea in urine were calculated. These values were converted to a rounded LOAEL of 3.5 microg Hg vapour/m(3) air. In analogy to the US EPA Report (U.S. Environmental Protection Agency 1997) and the European Position Paper (Pirrone et al. 2001), uncertainty factors of 30 and 50 were applied, resulting in a proposed reference concentration (RfC) in ambient air of 0.1 microg Hg vapour/m(3) and 0.07 microg Hg vapour/m(3), respectively. PMID- 20576545 TI - [Efficacy of systematic information and prescription of vaccine to implement the recommendations to prevent post-partum pertussis: A limited impact]. AB - OBJECTIVES: Despite official recommendations in 2004, antipertussis vaccine coverage in post-partum remains low. Measures used to date to improve the appliance of these recommendations were not implemented. The purpose of this study was to evaluate the effectiveness of a strategy of education and systematic prescription of antipertussis vaccine, on immunization coverage of mothers in the post-partum. PATIENTS AND METHODS: This was an analytical, interventional, monocentric study conducted on delivered patients, hospitalized between July 10th and 31st, 2009 in our establishment. Oral (twice: midwife and doctor) and written information about pertussis and order of vaccine were delivered in post-partum. RESULTS: No patient had reliable information on her vaccination status during hospitalization. According to the patients, information by midwife was provided in 70% of cases. At 6 weeks, the immunization coverage was 16% (10/61 patients), including 8% related to the intervention (vaccinated during postpartum) and 11% for fathers (7/61 fathers) with 7% newly vaccinated. Lack of time, omission in proliferation of information context in puerperium and low socio-economic backgrounds may have influenced the non-vaccination. However medical information is so far still perfectible as evidenced by the rate of patients actually sensitized and postponement vaccination after breastfeeding despite official recommendations. DISCUSSION AND CONCLUSION: Antipertussis vaccination care should also involve physicians before, during and after pregnancy, and pediatricians. PMID- 20576546 TI - [Age at onset of menarche: Results from the French Health Behaviour in School aged Children study]. AB - OBJECTIVE: To describe age at onset of menarche in a large nationally representative sample of French schoolgirls. PATIENTS AND METHODS: Age at onset of menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire. Median age at onset of menarche was estimated using Kaplan-Meier's method from a nationally representative sample of 2323 13 and 15 years old girls in school classrooms. Mean and standard deviation was also reported in the 1059 15 years old girls who had already experienced menarche. RESULTS: Median age at onset of menarche was 12.8 years (interquartile range: 12.0-13.6), as was mean age at onset of menarche (standard deviation 1.2 years). DISCUSSION AND CONCLUSION: Age at onset of menarche and its variability (as measured by standard deviation) have decreased in most developed countries and seems stabilised at 13.0+/-0.5 years: our results are in line with this trend. The age limit of 9 years seems more coherent to define early menarche in French girls. These results may have an important impact on medical management of early pubertal development. PMID- 20576547 TI - [Connective tissue and prolapse genesis]. AB - The pathophysiology of pelvic floor disorders still remains not well understood. Increasing age as well as vaginal multiparity are the main commonly accepted factors. The hypothesis of a defect of connective tissues of the pelvic floor with aging due to collagen deficiency and/or elastic fiber degradation is often highlighted. The issue of a potential protective role of HRT is also discussed although the recent results from the WHI would suggest a negative impact of HRT on urinary incontinence, especially when HRT is initiated in elderly women, far from the menopause. Nevertheless, environmental factors cannot explain the full pathogenesis of pelvic organ prolapse (POP) and the contribution of genetic factors to the development of pelvic floor disorders is widely recognized. Support for a genetic influence on POP derives from reports suggesting that heritability is a strong contributing factor and a familial history of POP is considered as a classical risk factor. However, the characterization of the underlying molecular mechanisms remains limited, since POP may be considered the end result of a multifactorial process leading to destruction of vaginal wall connective tissue. Experimental studies in mice with null mutations in the genes encoding different putative factors involved in elastic fibers remodeling and homeostasis are crucial in the understanding of the pathogenesis of POP. Mice with null mutation in the gene encoding lysyl oxidase-like 1 (LOXL1) or fibulin 5, demonstrate signs of elastinopathy including the development of a POP in the postpartum. Likewise, homeobox genes such as HOXA11, which are essential in the embryonic development of the urogenital tract might also be involved in the pathogenesis of POP. The better understanding of the underlying determinants of pelvic floor disorders with a special focus on genetic factors may offer new therapeutic strategies, in addition to or replacement of surgical procedures. PMID- 20576548 TI - [All about follicles...]. PMID- 20576549 TI - [Polyovular follicles]. AB - Folliculogenesis covers the sequential steps in the development of a follicle, from primordial to preovulatory. Most of the time, one follicle contains a single oocyte, but some follicles are polyovular in that they contain several. These follicles were considered earlier as pathological, but they are, actually, fairly common in several species, from mice to humans. The frequency of polyovular follicles (number of polyovular/total number of follicles) varies among species, <0.1% to 14% in the dog, and with age (more polyovular follicles during the prepubertal period). More than 20 oocytes (and even more than 100 in the marsupials like the opossum) may be present in a single follicle. These follicles may form during the earliest stages of follicle formation, due to an imbalance between somatic and germinal cells, which induces an incomplete germ cell cyst breakdown. In polyovular follicles, the quality (size and maturity) of the various oocytes is often heterogeneous. Numerous authors reported that polyovular follicles are able to reach ovulation and ovulate. Polyovular follicles, naturally found in several species, may also be induced by exposure to therapy or agents in the environment, especially with estrogen activity such as pesticides or diethylstilbestrol/DES. Polyovular follicles are also observed in the ovaries of mutated rodents. PMID- 20576550 TI - [Is neo-oogenesis in the adult ovary, a realistic paradigm?]. AB - It is a central dogma of female reproductive biology that oogenesis ceases around the time of birth in mammalian species. In 2004 and 2005, two studies were published by Johnson et al., in which they claimed that in the adult mouse ovary, neo-oogenesis takes place and originates from female germline stem cells that are present in either the ovarian surface epithelium or bone marrow. Following these publications, experiments showed that non-germinal stem cells could generate oocytes. However, in the mouse, ability of extra-ovarian stem cells to refurbish the ovary in new oocytes competent to ovulate, and subsequent existence of a spontaneous neo-oogenesis in the adult ovary in normal physiologic conditions, have been disputed. Morphologic studies performed in the adult mouse ovary showed that atresia of the immature follicle pool was strongly overestimated by Johnson et al., and that no intermediary stages of meiosis were seen. These observations led to the conclusion that adult female mice do not need neo-oogenesis for maintaining a normal reproductive function. However, a recent study have shown that female germline stem cells might be present in the ovarian surface epithelium in mice and humans. When sampled in GFP transgenic mice, cultured for a long period and transplanted into ovaries of sterilized mice, these cells underwent oogenesis and the mice produced offsprings. These new data support the possibility to experimentally restore fertility in women suffering from a premature ovarian failure. PMID- 20576551 TI - [Follicular fluid in mammals]. AB - Follicular fluid is a complex extracellular fluid, semi-viscous and yellow in colour, which accumulates in the antrum of ovarian follicles during their growing phase. Follicular fluid provides the microenvironment within which the cumulus oocyte complex matures and granulosa cells differentiate. Scientists agree that follicular fluid derives mainly from plasma via the vascular compartment in the follicle wall. However, it also contains factors produced locally by the follicle cells, the production of which varies during different reproductive states. The aim of this paper is to review current knowledge on the formation, composition and roles of follicular fluid. PMID- 20576552 TI - [Polycystic ovary syndrome: A model of follicular excess]. AB - Polycystic ovary syndrome (PCOS) is the most common etiology of menstrual disorders and hyperandrogenism. It is characterized by an excess of ovarian follicles. The mechanisms that underlie folliculogenesis disorder in PCOS appear to arise from primitive ovarian hyperandrogenism. This can be modulated by hormonal factors, such as LH or insulin. Ovarian hyperandrogenism results from a real theca cells dysfunction, whose origin is still poorly understood. It seems that complex genetic factors may be involved, but these have not yet been clearly identified. PCOS also results from granulosa cells dysfunction. For example, intra-ovarian factors, such as anti-mullerian hormone, are possibly involved in ovulation's disorders by blocking the physiological process of follicular recruitment. In turn, the oocyte could also be one of the actors possibly involved in the follicular excess in PCOS. PMID- 20576553 TI - [Screening for gestational diabetes mellitus: Is it time to revise the recommendations?]. AB - Universal screening for gestational diabetes mellitus (GDM) has been a topic of ongoing controversy for many years. In 2005, the French Health Authority concluded that no recommendation could be issued because of insufficient evidence. Recently, several studies have clarified the issues. It is now clearly established that women with GDM, including mild forms, are at increased risk of perinatal complications. Randomized controlled trials demonstrate that treatment to reduce maternal glucose levels improves perinatal outcomes. Today, the rationale for screening appears unquestionable. There are simple screening tests. However, it remains difficult to define threshold values because there is a strong, continuous association of maternal glucose levels with increased risks of adverse pregnancy outcomes. PMID- 20576555 TI - [How I... remove axillary sentinel lymph node under local anesthesia]. PMID- 20576554 TI - [Sentinel node biopsy after multiple breast and axillary surgeries]. AB - Sentinel node (SN) biopsy is considered as a standard of care in the staging of breast cancer. We report SN biopsy in a rare case of second ipsilateral subcutaneous recurrence in patient with previous left breast cancer initially treated by breast radiotherapy followed by mammectomy with axillary dissection and multiple mammoplasty. Lymphoscintigraphy was performed. Two axillary radioactive SNs were identified and removed without lymph node involvement at final histology. To conclude, re-operative axillary dissection by SN biopsy after previous axillary and breast surgeries is technically feasible. PMID- 20576556 TI - [Against the systematic practice of laparoscopy in infertility evaluation]. PMID- 20576558 TI - [A place for clinical research training during residentship]. PMID- 20576557 TI - [Diagnostic laparoscopy in current fertility practice: Pros]. PMID- 20576559 TI - [Experimental research on mechanical behavior of human placenta]. AB - OBJECTIVES: Determination of mechanical properties of human placenta. PATIENTS AND METHODS: Realisation of an experimental study using 80 human placentas and modelisation of this study using a finite element numerical model. Using the inverse analysis method, research of the parameters of placenta's behavior. RESULTS: Hyper-Visco-Elastic law written by Ogden, optimized for placenta with parameters: mu(1)=0.0001881Mpa, mu(2)=-0.000240Mpa, mu(3)=mu(4)=0Mpa and alpha(1)=2, alpha(2)=-8, alpha(3)=alpha(4)=0 in static condition. DISCUSSION AND CONCLUSION: The parameters enable an approach of the mechanical behavior of the placenta. They could be used in numerical modelisation. PMID- 20576560 TI - Influence of alcohol treatments on the activity of lipases immobilized on methyl modified silica aerogels. AB - The effects of alcohol treatment on the activity and loading amount of Candida rugosa lipase (CRL), Candida Antarctica lipase B (CALB) and Porcine Pancreas lipase (PPL) immobilized on methyl-modified silica aerogels were investigated, and the fluorescent analysis was used to explore the change of lipase hydrophobicity in aqueous solution caused by alcohols. It is found that alcohol types and the stages at which alcohol was added significantly influenced the performance of immobilized lipases through changing the hydrophobicity of the molecules. For CRL and PPL, five kinds of alcohol were added in the adsorption process, and n-butanol and isopropanol improved the apparent activity of CRL and PPL up to 2.5 times and 2 times those of the untreated ones, respectively; however, for CALB, it is better to activate the immobilized CALB after the adsorption process, and the apparent activity of CALB increased up to 2.76 times through n-butanol treatment. PMID- 20576561 TI - Enhanced sorption of polycyclic aromatic hydrocarbons from aqueous solution by modified pine bark. AB - To enhance removal efficiency of natural sorbent with polycyclic aromatic hydrocarbons (PAHs), single-solute and bi-solute sorption of phenanthrene and pyrene onto raw and modified pine bark were investigated. Pine bark was modified using Soxhlet extraction, saponification and acid hydrolysis, yielding six bark fractions with different chemical compositions. Raw pine bark exhibited high affinities with PAHs, and sorption was dominated by partitioning. The relatively nonlinear sorption isotherms of modified bark were attributed to the specific interaction between sorbate and aromatic core of sorbent. Comparison with lipid and suberin, lignin was the most powerful sorption medium, but which was almost completely suppressed by coexisting polysaccharide. After consuming polysaccharide by acid hydrolysis, sorption of pine bark fractions was notably increased (4-17 folds); and sorption of pyrene just decreased 16-34% with phenanthrene as a competitor. These observations suggest that pine bark is of great potential for PAHs removal and can be significantly promoted by acid hydrolysis for environmental application. PMID- 20576562 TI - Synthesis of lignin-base cationic flocculant and its application in removing anionic azo-dyes from simulated wastewater. AB - In this paper the Mannich reaction product of dimethylamine, acetone and formaldehyde was grafted onto hydroxymethylated lignin to form a lignin-base cationic polyelectrolyte (L-DAF). L-DAF samples with different cationic strengths and molecular weights were synthesized and characterized. Their performance as a cationic flocculant in removing three anionic azo-dyes (Acid Black, Reactive Red and Direct Red) from simulated dye wastewater was evaluated. The removal of anionic dyes by L-DAF was ascribed to two simultaneous mechanisms, which included coagulation by charge neutralization and flocculation by bridging. There was a different optimum dose of flocculant for each dye wastewater, at which dye removal can reach above 95%. Furthermore, a longer settling time and a lower solution pH increased the efficiency of the decolorization process. During the treatment, more than 89% of chemical oxygen demand (COD) reduction was achieved with sludge production being less than 5.4%. PMID- 20576563 TI - Potential odour emission measurement in organic fraction of municipal solid waste during anaerobic digestion: Relationship with process and biological stability parameters. AB - The aim of the present study is to investigate the correlation between microbial activity, i.e., biological stability measured by aerobic (OD(20) test) and anaerobic tests (ABP test), and odour emissions of organic fraction of municipal solid waste during anaerobic digestion in a full-scale treatment plant considering the three stages of the process (input, digested and post-digested waste). The results obtained indicated that the stabilization of the treated material reduces the odour impact measured by the olfactometric approach. Successive application of gas chromatography mass spectrometry (GC-MS) and electronic nose (EN) allowed the characterization of the different groups of volatile organic compounds (VOCs) responsible of odour impacts determining, also, their concentration. Principal component and partial least squares analyses applied to the EN and GC-MS data sets gave good regression for the OD(20) vs the EN and OD(20) vs the GC-MS data. Therefore, OD(20) reduction could be used as an odour depletion indicator. PMID- 20576564 TI - Investigation into the relationship between the gravity vector and the flow vector to improve performance in two-phase continuous flow biodiesel reactor. AB - The following study analyzes the performance of a continuous flow biodiesel reactor/separator. The reactor achieves high conversion of vegetable oil triglycerides to biodiesel while simultaneously separating co-product glycerol. The influence of the flow direction, relative to the gravity vector, on the reactor performance was measured. Reactor performance was assessed by both the conversion of vegetable oil triglycerides to biodiesel and the separation efficiency of removing the co-product glycerol. At slightly elevated temperatures of 40-50 degrees C, an overall feed of 1.2 L/min, a 6:1 M ratio of methanol to vegetable oil triglycerides, and a 1-1.3 wt.% potassium hydroxide catalyst loading, the reactor converted more than 96% of the pretreated waste vegetable oil to biodiesel. The reactor also separated 36-95% of the glycerol that was produced. Tilting the reactor away from the vertical direction produced a large increase in glycerol separation efficiency and only a small decrease in conversion. PMID- 20576565 TI - Milling pretreatment of sugarcane bagasse and straw for enzymatic hydrolysis and ethanol fermentation. AB - The effectiveness of ball milling (BM) and wet disk milling (WDM) on treating sugarcane bagasse and straw were compared. Pretreated materials were characterized by wide angle X-ray diffraction analysis, particle-size distribution and scanning electron microscopy and the effectiveness of pretreatments was evaluated by enzymatic hydrolysis and fermentation. Glucose and xylose hydrolysis yields at optimum conditions for BM-treated bagasse and straw were 78.7% and 72.1% and 77.6% and 56.8%, respectively. Maximum glucose and xylose yields for bagasse and straw using WDM were 49.3% and 36.7% and 68.0% and 44.9%, respectively. BM improved the enzymatic hydrolysis by decreasing the crystallinity, while the defibrillation effect observed for WDM samples seems to have favored enzymatic conversion. Bagasse and straw BM hydrolysates were fermented by Saccharomyces cerevisiae strains. Ethanol yields from total fermentable sugars using a C6-fermenting strain reached 89.8% and 91.8% for bagasse and straw hydrolysates, respectively, and 82% and 78% when using a C6/C5 fermenting strain. PMID- 20576566 TI - New xylanases to obtain modified eucalypt fibres with high-cellulose content. AB - Modified fibres with high-cellulose content were obtained with two new bacterial xylanases from families 11 and 5. These xylanases were applied separately or simultaneously in a complete ECF (Elemental Chlorine Free) bleaching sequence. Both xylanases improved delignification and bleaching during the sequence and a synergistic effect of the enzymes was observed on several pulp and paper properties. The xylanases boosted the release of xylooligosaccharides branched with hexenuronic acids (HexA), giving rise to fibres with a reduced HexA and xylose content. However, these effects depended on the xylanase used, being the family 11 enzyme more efficient than the family 5 xylanase. Effluent properties such as absorbance spectra UV/Vis, COD and colour were affected by the enzymatic sequences as a consequence of the dissolution of lignin and xylooligosaccharides. Some changes in the fibre morphology were also produced without affecting the final paper strength properties. PMID- 20576567 TI - Production of medium-chain triacylglycerols from corn oil: optimization by response surface methodology. AB - Structured lipids (SLs) having long-chain fatty acids at sn-2 and medium-chain caprylic acid (CA, 8:0) at their sn-1,3-positions from corn oil (CO) were obtained and optimized by response surface methodology (RSM) with a three-level, three-factor face-centered cube design. Compositions of triacylglycerol species (TAGs) in SLs were also investigated by reverse-phase high performance liquid chromatography. Lipozyme TL IM from Thermomyces lanuginosa was used for the acidolysis of CO with CA in n-hexane. The effects of substrate molar ratio, enzyme amount, and reaction time on CA incorporation into CO were optimized. The optimum conditions were 13.2% (wt.) enzyme, 3.9:1 caprylic acid/corn oil molar ratio, and 3.1 h reaction time. At optimum conditions, 21.5 +/- 0.8 mol.% caprylic acid containing SLs was obtained. This product was characterized by 50% of triacylglycerol species with equivalent carbon number (ECN) C30, C32, C36, and C38, and 50% of triacylglycerol species with ECN C42, C44, and C46. PMID- 20576568 TI - Application of response surface methodology and artificial neural networks for optimization of recombinant Oryza sativa non-symbiotic hemoglobin 1 production by Escherichia coli in medium containing byproduct glycerol. AB - Production of recombinant Oryza sativa non-symbiotic hemoglobin 1 (OsHb1) by Escherichia coli was maximized in shake-flask cultures in media containing tryptone, yeast extract, sodium chloride and byproduct glycerol from biodiesel production. Response surface methodology (RSM) and artificial neural networks (ANNs), followed by multiple response optimization through a desirability function were applied to evaluate the amount of OsHb1 produced. The results obtained by the application of ANNs were more reliable since better statistical parameters were obtained. The optimal conditions were (gL(-1)), tryptone, 42.69; yeast extract, 20.11; sodium chloride, 17.77; and byproduct glycerol, 0.33. A maximum recombinant protein concentration of 3.50gL(-1) and a minimum biomass concentration of 18.48gL(-1) were obtained under these conditions. Although the concentrations of tryptone, yeast extract and sodium chloride are relatively high, the increase in the yield with respect to biomass formed (Y(P/X)) overcomes this disadvantage. PMID- 20576569 TI - Using of Rhizopus arrhizus as a sensor modifying component for determination of Pb(II) in aqueous media by voltammetry. AB - For the sensitive determination of Pb(II) from aqueous solutions, a new voltammetric biosensor based on carbon paste electrode modified with Rhizopus arrhizus was developed. The preconcentrated ions at open circuit were reduced by using differential pulse stripping voltammetry technique. The obtained current values were related to the concentration of Pb(II) in the solutions. The best results were achieved at pH 7 with 0.01 M Tris-HCl buffer solution applying a preconcentration time of 12 min. The linear range for the biosensor was found to be within 1.0 x 10(-7)-1.25 x 10(-5) M, with a detection limit of 0.5 x 10(-8) M. The selectivity of the microbial biosensor was explored by adding interfering heavy metals to accumulation medium one by one, and their matrix effects were also investigated in the model metal solutions. Energy dispersive X-ray spectra analysis were applied to show the specific effect of the fungal biomass on the Pb(II) determination. PMID- 20576570 TI - Heavy metal removal and crude bio-oil upgrading from Sedum plumbizincicola harvest using hydrothermal upgrading process. AB - The main aim of this study was to separate heavy metals and yield crude bio-oil from a heavy metals hyperaccumulator harvest, Sedum plumbizincicola, through hydrothermal upgrading process. Parameters such as granularity, temperature, pressure, and duration were examined for their effect on the removal efficiency of heavy metals and upgrading efficacy of crude bio-oil. Maximum heavy metal removal efficiency of >99% and crude bio-oil upgrading efficiency of >63% were attained with an 18 mesh (1mm) granularity, and 22.1MPa at 370 degrees C in the presence of 10mg/L additives for 60s. Under these optimized conditions, an oil phase (mostly composed of phenolic hydrocarbons and derivatives), a water phase raffinate containing Zn(2+) (0.39g/L), Pb(2+) (0.10g/L), Cu(2+) (0.16g/L), and a solid phase (the hydrothermal upgrading residue, which completely satisfies the limit set by China legislation related to biosolids disposal, were obtained). PMID- 20576571 TI - Steam treatment of digested biofibers for increasing biogas production. AB - The aim of this study was to elucidate the effect of steam pretreatment on the biomethane potential of biofibers from digested manure. These biofibers were treated for 15 min with steam in a pressure vessel. The effect of steam treatment temperature, solids content, catalyst concentration and time of pre-soaking on the methane potential of the biofibers was determined. The highest increase of methane production from steam-treated biofibers compared to untreated biofibers was 67% and was achieved at 155 degrees C with addition of 2.1% w/w H2SO4. Also higher treatment temperatures (180 degrees C without addition of acid) improved the methane production, but only by 29% compared to untreated biofibers. Long pre soaking treatment (24 h) and high acid concentration increased the risk of inhibition of the biogas process. The energy from the increased methane production after steam treatment was between 15 and 121 kW h (t WW)(-1) (wet weight of untreated biofibers). PMID- 20576572 TI - New aryldithiolethione derivatives as potent histone deacetylase inhibitors. AB - A series of dithiolethione derivatives was synthesized and the in vitro HDAC inhibitory activity was tested. The most active compounds, 1 and 2, exhibited an IC(50) in nM range with a strong hyperacetylation of histone H4 in A549 cells. The HDAC inhibitory activity comparable to that of SAHA and the inhibition of A549 cell proliferation suggest that these compounds are worthy of further studies as potential anticancer agents. PMID- 20576573 TI - Pharmacophore and structure-activity relationships of integrase inhibition within a dual inhibitor scaffold of HIV reverse transcriptase and integrase. AB - Rational design of dually active inhibitors against human immunodeficiency virus (HIV) reverse transcriptase (RT) and integrase (IN) has proved viable with 1-[(2 hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) type of non-nucleoside RT inhibitors (NNRTIs). To establish the pharmacophore and study the structure activity relationships (SAR) of integrase inhibition within a previously disclosed RT/IN dual inhibitor scaffold, new analogues featuring substitution at different sites of the HEPT ring were designed and synthesized. These studies have revealed an IN inhibition pharmacophore that is merged with the known RT pharmacophore through a shared C-6 benzyl group. Further SAR also demonstrated that optimal IN inhibition within our dual inhibitor scaffold requires a regiospecific (N-1) diketoacid (DKA)-carrying pendant with a certain length. PMID- 20576574 TI - Targeting efflux pumps-In vitro investigations with acridone derivatives and identification of a lead molecule for MDR modulation. AB - To search multi drug resistance modulators, acridones carrying hydroxyl amine substituent at N-10 and COOH/Cl at C-4 were investigated for their interactions with the three components of efflux pump viz. P-gp, ATP, and Mg(2+). Experimental and theoretical results indicated that the compounds with COOH group at C-4 interact with P-gp and Mg(2+) while other set of compounds with Cl at C-4 interact with ATP and Mg(2+). Spot assay and R6G influx/efflux assay of compound 3 using Candida albicans showed decrease in the fungal growth and efflux of R6G, respectively, in presence of compound 3 suggesting the suitability of this compound for MDR modulation. PMID- 20576575 TI - Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating alpha-asarone-based HMG CoA reductase inhibitors. AB - A series of alpha-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of alpha-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity. PMID- 20576576 TI - Design, synthesis, and biological evaluation of novel coxsackievirus B3 inhibitors. AB - The synthesis and SAR study of a novel class of coxsackievirus B3 (CVB3) inhibitors are reported. These compounds could be considered as the 6 chloropurines substituted at position 9 with variously substituted bicyclic scaffolds (bicyclo[2.2.1]heptane/ene-norbornane or norbornene). The synthesis and biological evaluation of 31 target compounds are described. Several of the analogues inhibited CVB3 in the low micromolar range (0.66-2muM). Minimal or no cytotoxicity was observed. PMID- 20576577 TI - Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophora. AB - Eight new indole alkaloids, alpneumines A-H (1-8) were isolated from the Malaysian Alstonia pneumatophora (Apocynaceae) and their structures were determined by MS and 2D NMR spectroscopic methods. Alpneumines E and G (5 and 7), vincamine, and apovincamine showed anti-melanogenesis in B16 mouse melanoma cells. PMID- 20576578 TI - ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium dependent glucose co-transporter 2 (SGLT2) inhibitors. AB - A series of 2-substituted C-aryl glucosides have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of an appropriate ortho substituent at the proximal phenyl ring adjacent to the glycosidic bond was found to improve SGLT2 inhibitory activity and dramatically increase selectivity for hSGLT2 over hSGLT1. Selected compounds were investigated for in vivo efficacy. PMID- 20576579 TI - Imaging applications in multicatheter brachytherapy for soft tissue sarcomas. AB - Multicatheter brachytherapy can be applied as a monotherapy or in combination with external beam radiotherapy as an adjuvant treatment for soft tissue sarcoma. Successful application of brachytherapy in the treatment of soft tissue sarcoma requires implementation of multiple imaging modalities during preoperative and postoperative planning. Preoperative imaging is essential in planning local therapy for soft tissue sarcoma in that it defines the proximity of the tumor to adjacent critical structures, predicts the likelihood of close or positive surgical margins, and aids in defining the target volume for a brachytherapy implant. In the postoperative setting, imaging is utilized to assess the accuracy of target volume coverage and integrity of the implant, as well as in three dimensional treatment planning. PMID- 20576581 TI - Cadmium impairs albumin reabsorption by down-regulating megalin and ClC5 channels in renal proximal tubule cells. AB - BACKGROUND: Cadmium (Cd) is a potent nephrotoxicant that impairs the reabsorptive and secretory functions of the renal proximal tubule, leading to albuminuria. OBJECTIVES: To gain insights into the mechanisms of Cd-induced albuminuria, we investigated effects of Cd on the expression of megalin and chloride channel 5 (ClC5), two key players in albumin-receptor-mediated endocytosis. METHODS: We used quantitative polymerase chain reaction, Western blotting, the albumin endocytosis assay, and confocal microscopy to evaluate effects of Cd on the expression and regulation of megalin and ClC5 in cultured LLC-PK1 cells, a pig proximal tubular cell model. RESULTS: Ten micromolar cadmium chloride (CdCl2) caused a significant time- and dose-dependent decrease in both mRNA and protein levels of megalin and ClC5, whereas no changes resulted from exposure to other divalent metals (zinc chloride, manganese chloride, magnesium chloride, and nickel chloride). After inhibiting protein synthesis using cycloheximide (CHX), we found that levels of both megalin and ClC5 were lower in Cd-challenged cells than in cells treated with Cd or CHX only, which is consistent with reduced translation and/or posttranslational down-regulation. Moreover, Cd-induced degradation of megalin and ClC5 was abolished by the lysosomal pathway inhibitor bafilomycin A-1 but not by the proteasome system blocker MG-132, suggesting that the enhanced proteolysis was occurring via lysosomes. Using confocal microscopy, we observed a remarkable reduction of fluoroisothiocyanate (FITC)-labeled albumin uptake after Cd exposure. CONCLUSIONS: We found that Cd reduced the transcriptional expression of megalin and ClC5 and, at the same time, increased the degradation of megalin and ClC5 proteins via the lysosomal pathway in an in vitro model of renal proximal tubular cells. Overall, these results provide valuable insights into the molecular mechanisms by which Cd impairs luminal protein reabsorption by renal proximal tubules. PMID- 20576580 TI - Potential influence of climate change on vector-borne and zoonotic diseases: a review and proposed research plan. AB - BACKGROUND: Because of complex interactions of climate variables at the levels of the pathogen, vector, and host, the potential influence of climate change on vector-borne and zoonotic diseases (VBZDs) is poorly understood and difficult to predict. Climate effects on the nonvector-borne zoonotic diseases are especially obscure and have received scant treatment. OBJECTIVE: We described known and potential effects of climate change on VBZDs and proposed specific studies to increase our understanding of these effects. The nonvector-borne zoonotic diseases have received scant treatment and are emphasized in this paper. DATA SOURCES AND SYNTHESIS: We used a review of the existing literature and extrapolations from observations of short-term climate variation to suggest potential impacts of climate change on VBZDs. Using public health priorities on climate change, published by the Centers for Disease Control and Prevention, we developed six specific goals for increasing understanding of the interaction between climate and VBZDs and for improving capacity for predicting climate change effects on incidence and distribution of VBZDs. CONCLUSIONS: Climate change may affect the incidence of VBZDs through its effect on four principal characteristics of host and vector populations that relate to pathogen transmission to humans: geographic distribution, population density, prevalence of infection by zoonotic pathogens, and the pathogen load in individual hosts and vectors. These mechanisms may interact with each other and with other factors such as anthropogenic disturbance to produce varying effects on pathogen transmission within host and vector populations and to humans. Because climate change effects on most VBZDs act through wildlife hosts and vectors, understanding these effects will require multidisciplinary teams to conduct and interpret ecosystem-based studies of VBZD pathogens in host and vector populations and to identify the hosts, vectors, and pathogens with the greatest potential to affect human populations under climate change scenarios. PMID- 20576584 TI - [Stereotaxic brain radiosurgery in Hungary 1991-2009]. AB - Stereotaxic brain radiosurgery as a non-invasive type of local treatment appeared as a therapeutic approach of intracranial lesions in the middle of the last century. Originally it was developed for treating functional disorders but with the evolution of their medication the clinical need increasingly turned to treating pathomorphological intracerebral target volumes. A review of the indication's historical changes and the installation, methods, results and perspectives of Hungarian brain radiosurgery are presented. During the above mentioned period 2565 patient have been treated in five institutes of Hungary: 52% for brain metastases, 29.5% for benignomas, 12% for arteriovenous malformations, 6% for primary malignant brain tumors and 0.5% for functional disorders. Local tumor control of 86% and median survivals among patients with metastasis of 24 months in RPA class 1, 8.5 months in RPA 2 and 3.4 months in RPA 3 were reported. These results are comparable with those in the literature. Hopefully with a change in the therapeutic approach and better organization of patients' management, stereotaxic brain radiosurgery will be integrated into everyday routine in Hungary. PMID- 20576582 TI - Urinary porphyrin excretion in neurotypical and autistic children. AB - BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU). OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism. METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism. RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received. CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent. PMID- 20576585 TI - [Surgical treatment of cancer at the beginning of the third millenium--based on the 2004 Krompecher Memorial Lecture of the Society of Hungarian Oncologists]. AB - The author presents a historical overview of cancer surgery of the last century. At the last quarter of the century the main characteristic of this process has been the significant extension of surgical radicality. Three new surgical methods appeared and have been routinely used at the Surgical Clinic of the Szeged University School, to increase surgical radicality, to improve survival rate without impairing the postoperative quality of life. 1.) Subtotal colectomy (STC) involves an extended resection of the colon over the splenic flexure. In a period of 8 years a total of 72 STCs were performed for the treatment of large bowel obstructions or symptomatic stenosis caused by cancer of the left colon. STC offers: a) one stage treatment for colonic obstruction in emergency surgery, b.) removal of the tumor with sufficient oncological radicality, c.) primary reconstruction of the digestive tract, with a safe ileocolic anastomosis even in emergency cases. Based on a study about postoperative quality of life of STC operated patients, it proved to be normal. 2.) The author reports a total of 108 middle and low third rectal cancer cases operated on by total mesorectal excision (TME) by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The author succeeded in 60% of cases to perform an anterior resection with preservation of the anal sphincter, and to decrease the early (within two years after surgery) local recurrence rate from 14.5% to 6.4%, compared to the group of patients operated on by traditional technic. 3.) A total of 154 patients with locally advanced - stage IV - colorectal cancer underwent extended surgery of multivisceral resections as a treatment of cancer process involving adjacent abdominal organs. Surgery was performed to treat advanced cancer of the colon in 112 cases and the one of the rectum in 42 cases. The mortality rate was 7% in the colon cancer group, and 12% in the group of rectal cancer patients. In their tumor-free postoperative period 90% of colon cancer patients and 95% of rectal cancer patients had an improved quality of life. The 5 years survival rate was 40% in the colon group and 22% in the rectal cancer group. In the group of patients having more than 3 simultaneously tumorous organs, in spite of the multiple organ resections, no 5 years survival has been recorded. PMID- 20576587 TI - [Laparoscopic surgery in colorectal tumors]. AB - The minimally invasive technique, by means of the undoubted advantages of the method, has become fully accepted in the surgical treatments of the most benign and functional diseases. Today it has been proven that the laparoscopic technique is safely usable also in the surgical treatment of colorectal tumors. The authors, analyzing their own and the international experiences, present the laparoscopic surgical treatment of colorectal tumors. Seventy-four patients were treated with laparoscopic-assisted colorectal intestinal resection in the Department of Surgery of the University of Szeged between January 1, 2005 and December 31, 2008. The surgical indication was neoplastic colorectal lesion in 40 cases. The average age of them was 64 years (from 36 to 89 years). Four patients belonged to the risk group of ASA I, 11 patients to ASA II, 24 to ASA III, and one to ASA IV. Twenty-six patients underwent rectosigmoideal resection, 2 had rectal exstirpation, 9 had right hemicolectomy and one had left hemicolectomy. There were no surgical or postoperative complications. Four conversions and in one case a reoperation occurred due to adhesion ileus. The startup of the passage (2.4 days, on average) and the possibility of nourishing per os were significantly shortened. The histological processes of specimens justified tumor free oral, aboral and circumferential resection in all cases. Summarizing our own and international experiences it can be stated that the laparoscopic surgeries performed due to colorectal tumors are safe, and are also appropriate with respect to oncosurgery. There are a number of benefits for the patients mainly in the early postoperative period (faster recovery, shorter hospitalization) and their long-term survival results are good as well. PMID- 20576588 TI - [Surgical treatment of liver metastasis in colorectal cancer with simultaneous liver resection]. AB - Metastatic liver disease is a challenging and life-threatening situation often with dismal prognosis. Nearly half of the patients with colorectal cancer develop liver metastasis during the course of their diseases. Hepatic resection is the treatment of choice in patients with colorectal liver metastasis. This study was conducted to compare the results of patients undergoing simultaneous liver and colorectal resection for synchronous liver metastasis and of those for whom a colorectal and liver resection was made separately. A retrospective analysis was performed on 1597 patients who underwent surgery because of colorectal cancer between January 1999 and December 2008. The results of the treatment were separately evaluated in case of the 152 patients who had liver metastasis. The proportion of the liver metastasis was 9.52%. The metastases arose in 40.8% from the rectum and in 31.8% from the sigmoid colon. It proved to be inoperable in 109 (71.7%) of the 152 patients who had liver metastasis. Simultaneous liver resection was performed because of synchronous metastasis in 14 (32.6%) cases (Group 1) and two step resection in 29 (67.4%) cases (Group 2). In case of synchronous operations only minor liver surgery was done. The mean size of the metastasis was 2.6 cm in diameter in Group 1 and 4.6 cm in Group 2 (p<0.005). The transfused blood volume was 0.3 U/patient. Only minor complications could be observed in Group 1. The hospitalization was 13.1 days in Group 1 and 11.7 days in Group 2. The mean survival time was 37.3 and 47.9 months (p<0.005). Simultaneous liver resection seems to be a safe procedure on those patients who develop small metastases with a limited number. However, the optimal timing of the liver resection and the identification of patients who will have the greatest benefit in survival still remain obscure. PMID- 20576589 TI - [Clinical and histopathological results after the neo-adjuvant treatment of advanced rectal tumors]. AB - The role of the surgical intervention is decisive in treating colorectal tumors. The neo-adjuvant radio-chemotherapy has improved the efficacy of the treatment of advanced rectum tumors. In order to decrease the size and stage of advanced rectal carcinoma and to increase the rate of resecability, we introduced neoadjuvant radio-chemotherapy. We carried out neo-adjuvant and surgical treatment in case of 67 patients with rectal adenocarcinoma (T 2-4 N 1-2 M 0 ) between June 1, 2005 and July 31, 2008. The average age of the patients was 61.2 years, the division according to sex was 44 males/23 females. Regarding the local stage of the rectal process or the proximity to the sphincter, we applied radio chemotherapy (radiotherapy 25 times altogether 45 Gy and on the first and last week for 5-5 days they received 350 mg/m 2 /day 5-FU and 20 mg/m 2 /day leucovorin chemotherapy, recently complemented with 3 x 1.8 Gy advanced boost radiation aiming at the macroscopic tumor site with security zone). Patients underwent surgery 8 weeks on average after restaging examinations. Thirty-eight patients underwent anterior rectal resection with double stapler procedure; there were 18 abdominoperineal rectal extirpations, 7 Hartmann operations and 4 per annum excisions. Compared to the preoperative staging, the histological evaluation of the resected specimens showed total remission (pT 0 N 0 ) in 11% and partial remission in 43%. The morbidity necessitating reoperation was 5.9%, without mortality and suture insufficiency. The long-term neo-adjuvant oncological treatment led to down-staging of rectal tumors in most cases and increased the resecability and rate of resection operations. PMID- 20576590 TI - [Changes in the diagnostic and therapeutic strategies of non-small cell lung cancer]. AB - Major advancements have been made in the clinical management of non-small cell lung cancer (NSCLC) in the past decade. This development involved the introduction of pemetrexed and several targeted therapies (bevacizumab, erlotinib, gefitinib) in the first and second line treatments of NSCLC. Novel maintenance therapeutic strategies for NSCLC (erlotinib) and for non-squamous NSCLC (pemetrexed, bevacizumab+erlotinib) have also been developed resulting in a significant improvement in patient's survival. These changes have modified registrations of various drugs and require continuous update of guidelines and reimbursement schemes as well. These advantages are based on refinement of differential diagnosis of NSCLC and on the development of molecular predictive markers. Our aim is to summarize the changes in the diagnosis and therapy of NSCLC and to present the altered therapeutic scheme. PMID- 20576591 TI - [The role of chemotherapy in pediatric medulloblastoma]. AB - Medulloblastoma is one of the most frequent brain tumors in childhood. The mortality of medulloblastoma decreased significantly during the last few decades, which was the result of the better surgical and radiotherapeutic methods and of the development of chemotherapy. The aim of this publication is the critical review of the present chemotherapeutic treatment. The new therapeutic trials based on the molecular genetic mechanism of these tumors are also mentioned. PMID- 20576592 TI - [Role of hypnosis and hypno-suggestions methods in the complex therapy of tumor patients]. AB - Besides more conventional tumor risks, depression and negative life events are significant risk factors in cancer here in Hungary, therefore oncopsychology is increasingly important. We discuss traumatizing effects of the diagnosis and invasive diagnostic and therapeutic procedures from the viewpoint of altered state of consciousness. During stress and hypnosis brain functioning is altered in a similar way, which can be seen both in the patient's symptoms and his/her physiological and neuroimaging findings. In trance state patients part from reality, they no longer communicate conventionally or maturely. Hypnosis is characterized not only by physical and mental changes, but important unique social interactions as well. These interactions affect the endocrine and immune system and the mental state of the patient, they strengthen and synchronize resources and help posttraumatic growth. Since in the stress induced spontaneous altered state of consciousness the susceptibility to suggestions is increased, suggestive communication can be used effectively and it can even result in formal hypnosis induction. Under the strong time and mental pressure characterizing the work of the oncologic departments, it might help the staff to improve the cooperation with the patient if staff members, physicians and nurses as well, are aware of the nature and the neurophysiologic background of the spontaneous trance state induced by the life-threatening diagnosis of cancer. PMID- 20576593 TI - [The status of domestic PET/CT attendance in the light of the waiting list data]. AB - The aim of the study is to demonstrate the diagnostic and geographical distribution of the domestic PET/CT examinations financed by the OEP based on the data from the waiting list of the past 4 years. The analysis of the demonstrated data can support the rational usage of PET/CT examination contingents in the domestic oncological attendance, which has growing importance. PET examinations with oncological aims have started in Debrecen more than 10 years ago. In 2005 already 1500 PET examinations have been carried out. According to the governmental regulation accepted in 2006, OEP ensures the financing of the three PET/CT centers until 2012, which means 12,000 examinations in 2012. However, the number of domestic oncological patients requiring PET/CT examinations can reach the number of 20,000-30,000 patients. The study summarizes the number of patients who applied for PET/CT examinations for the first time and later again between 2006 and 2010, based on the data of the waiting list, and the change of the patient assigning diagnosis and the number of examinations carried out with 18F FDG and with 11C-methionine. The study demonstrates the number of examinations by counties which characterize the population's access to PET/CT. The assigning diagnosis in 2007 was already widespread and focused on problems. After the regulation came in to force in 2008 the possibilities significantly decreased. Clinical cases which were efficiently examined with PET/CT earlier were left out from the indication list. The distribution by county is uneven, although the number of examinations increases year by year. The number of repeated examinations increases as well. As a conclusion, the annual PET/CT examination contingents are constantly exploited. This might seem sufficient, because the method has not become a part of the oncological routine in all counties. Although the current indication list includes the most frequent oncological cases requiring PET/CT, the abandoning of the less frequent ones narrowed the professional latitude, which is disadvantageous for the patients suffering from such diseases. The radiopharmacon supply of PET/CT centers is inadequate thus they cannot provide modern oncological diagnostic attendance in case of frequent types of cancer (such as prostate). In the long run the growing number of repeated PET/CT examinations built in the oncological professional protocol has to be taken into account. PMID- 20576594 TI - [Correlation between microsatellite instability and morphology in colorectal cancer]. AB - Microsatellite instability (MSI) influences the development and clinical course of colorectal cancers (CRCs) and induce specific morphological alterations of such neoplasms, therefore hematoxylin-eosin (H&E) based histology allows to predict the microsatellite status of a given tumor. The aim of this article is to demonstrate clinicopathological features that are useful in recognition of microsatellite-stable and -unstable CRCs on routine histological examination. In the Center of Surgical and Molecular Pathology of National Institute of Oncology, from 384 CRC cases 26 hereditary non-polyposis colorectal cancers (HNPCC), 22 sporadic high-level microsatellite-instable (MSI-H) cancers and 76 microsatellite stable (MSS) or low-level MSI (MSI-L) CRCs were selected on the basis of the localization, clinical stage, microsatellite status, and patient age at the time of the diagnosis. Our results showed that we can recognize MSS/MSI-L carcinomas, HNPCCs and sporadic MSI-H tumors with high probability on the base of clinicopathological features like patient's age, tumor localization, clinical stage and histological characteristics of CRCs, even if the genetic MSI test is not available. The main morphological characteristics related to microsatellite instability are intratumoral or stromal infiltrating lymphocytes/leukocytes, large, vesicular nuclei with prominent nucleoli, and expansive infiltrative edge of the tumors. Careful and detailed morphological analysis of colorectal cancers helps to select the appropriate molecular method to determine the molecular features that influence the clinical care of patients and allow to consider the most appropriate anti-tumor therapy. PMID- 20576595 TI - [Adenomyosis of the common bile duct]. AB - A woman 80 years of age had diffuse adenomyosis in the wall of the choledochus, near to the papilla of Vater. The lesion caused icterus and was operated (partial pancreatoduodenectomy). Adenomyosis should be considered in the differential diagnosis of obstructive jaundice. PMID- 20576596 TI - [Abstracts of the 17th Primary Prevention Forum for the "Prevention of Health Harming Addictions". 20 May 2010 Budapest, Hungary]. PMID- 20576599 TI - A novel glycerophosphodiester phosphodiesterase, GDE5, controls skeletal muscle development via a non-enzymatic mechanism. AB - Mammalian glycerophosphodiester phosphodiesterases (GP-PDEs) have been identified recently and shown to be implicated in several physiological functions. This study isolated a novel GP-PDE, GDE5, and showed that GDE5 selectively hydrolyzes glycerophosphocholine (GroPCho) and controls skeletal muscle development. We show that GDE5 expression was reduced in atrophied skeletal muscles in mice and that decreasing GDE5 abundance promoted myoblastic differentiation, suggesting that decreased GDE5 expression has a counter-regulatory effect on the progression of skeletal muscle atrophy. Forced expression of full-length GDE5 in cultured myoblasts suppressed myogenic differentiation. Unexpectedly, a truncated GDE5 construct (GDE5DeltaC471), which contained a GP-PDE sequence identified in other GP-PDEs but lacked GroPCho phosphodiesterase activity, showed a similar inhibitory effect. Furthermore, transgenic mice specifically expressing GDE5DeltaC471 in skeletal muscle showed less skeletal muscle mass, especially type II fiber-rich muscle. These results indicate that GDE5 negatively regulates skeletal muscle development even without GroPCho phosphodiesterase activity, providing novel insight into the biological significance of mammalian GP-PDE function in a non-enzymatic mechanism. PMID- 20576600 TI - A new allergen from ragweed (Ambrosia artemisiifolia) with homology to art v 1 from mugwort. AB - Art v 1, the major pollen allergen of the composite plant mugwort (Artemisia vulgaris) has been identified recently as a thionin-like protein with a bulky arabinogalactan-protein moiety. A close relative of mugwort, ragweed (Ambrosia artemisiifolia) is an important allergen source in North America, and, since 1990, ragweed has become a growing health concern in Europe as well. Weed pollen sensitized patients demonstrated IgE reactivity to a ragweed pollen protein of apparently 29-31 kDa. This reaction could be inhibited by the mugwort allergen Art v 1. The purified ragweed pollen protein consisted of a 57-amino acid-long defensin-like domain with high homology to Art v 1 and a C-terminal proline-rich domain. This part contained hydroxyproline-linked arabinogalactan chains with one galactose and 5 to 20 and more alpha-arabinofuranosyl residues with some beta arabinoses in terminal positions as revealed by high field NMR. The ragweed protein contained only small amounts of the single hydroxyproline-linked beta arabinosyl residues, which form an important IgE binding determinant in Art v 1. cDNA clones for this protein were obtained from ragweed flowers. Immunological characterization revealed that the recombinant ragweed protein reacted with >30% of the weed pollen allergic patients. Therefore, this protein from ragweed pollen constitutes a novel important ragweed allergen and has been designated Amb a 4. PMID- 20576601 TI - The rapid-onset dystonia parkinsonism mutation D923N of the Na+, K+-ATPase alpha3 isoform disrupts Na+ interaction at the third Na+ site. AB - Rapid-onset dystonia parkinsonism (RDP), a rare neurological disorder, is caused by mutation of the neuron-specific alpha3-isoform of Na(+), K(+)-ATPase. Here, we present the functional consequences of RDP mutation D923N. Relative to the wild type, the mutant exhibits a remarkable approximately 200-fold reduction of Na(+) affinity for activation of phosphorylation from ATP, reflecting a defective interaction of the E(1) form with intracellular Na(+). This is the largest effect on Na(+) affinity reported so far for any Na(+), K(+)-ATPase mutant. D923N also affects the interaction with extracellular Na(+) normally driving the E(1)P to E(2)P conformational transition backward. However, no impairment of K(+) binding was observed for D923N, leading to the conclusion that Asp(923) is specifically associated with the third Na(+) site that is selective toward Na(+). The crystal structure of the Na(+), K(+)-ATPase in E(2) form shows that Asp(923) is located in the cytoplasmic half of transmembrane helix M8 inside a putative transport channel, which is lined by residues from the transmembrane helices M5, M7, M8, and M10 and capped by the C terminus, recently found involved in recognition of the third Na(+) ion. Structural modeling of the E(1) form of Na(+), K(+)-ATPase based on the Ca(2+)-ATPase crystal structure is consistent with the hypothesis that Asp(923) contributes to a site binding the third Na(+) ion. These results in conjunction with our previous findings with other RDP mutants suggest that a selective defect in the handling of Na(+) may be a general feature of the RDP disorder. PMID- 20576602 TI - Regulation of sodium-calcium exchanger activity by creatine kinase under energy compromised conditions. AB - Na(+)/Ca(2+) exchanger (NCX) is one of the major mechanisms for removing Ca(2+) from the cytosol especially in cardiac myocytes and neurons, where their physiological activities are triggered by an influx of Ca(2+). NCX contains a large intracellular loop (NCXIL) that is responsible for regulating NCX activity. Recent evidence has shown that proteins, including kinases and phosphatases, associate with NCX1IL to form a NCX1 macromolecular complex. To search for the molecules that interact with NCX1IL and regulate NCX1 activity, we used the yeast two-hybrid method to screen a human heart cDNA library and found that the C terminal region of sarcomeric mitochondrial creatine kinase (sMiCK) interacted with NCX1IL. Moreover, both sMiCK and the muscle-type creatine kinase (CKM) coimmunoprecipitated with NCX1 using lysates of cardiacmyocytes and HEK293T cells that transiently expressed NCX1 and various creatine kinases. Both sMiCK and CKM were able to produce a recovery in the decreased NCX1 activity that was lost under energy-compromised conditions. This regulation is mediated through a putative PKC phosphorylation site of sMiCK and CKM. The autophosphorylation and the catalytic activity of sMiCK and CKM are not required for their regulation of NCX1 activity. Our results suggest a novel mechanism for the regulation of NCX1 activity. PMID- 20576604 TI - Myosin VI is differentially regulated by DNA damage in p53- and cell type dependent manners. AB - Myosin VI is an unconventional motor protein and functions in a variety of intracellular processes such as cell migration, vesicular trafficking, and homeostasis of the Golgi complex. Previously, we found that myosin VI is up regulated in RKO, LS174T, and H1299 cells by DNA damage in a p53-dependent manner and mediates the pro-survival function of p53. Here, we showed that the levels of myosin VI protein were markedly inhibited in MCF7 and LNCaP cells by topoisomerase I-II inhibitors. However, the levels of myosin VI transcript were decreased only by topoisomerase I inhibitors. We also found that the levels of myosin VI protein were markedly inhibited in MCF7 cells by wild-type p53 but not tumor-derived mutant p53. Surprisingly, we found that the level of myosin VI transcript was slightly increased instead of decreased in MCF7 cells by p53, suggesting that a mechanism other than transcriptional repression is involved. Additionally, we found that on the myosin VI promoter, the level of acetylated histone H3 was markedly decreased, whereas that of p53 and acetylated histone H4 was slightly increased in MCF7 cells upon treatment with topoisomerase I-II inhibitors. Finally, we showed that overexpression of myosin VI enhances, whereas knockdown of myosin VI decreases, DNA damage-induced stabilization of p53, and consequently, knockdown of myosin VI de-sensitizes MCF7 cells to DNA damage induced apoptosis. Taken together, as a mediator of the p53 pro-survival pathway and a marker of malignancy in some tumors, differential regulation of myosin VI in various tumor cells by topoisomerase inhibitors dictates whether knockdown of myosin VI inhibits, rather than enhances, the susceptibility of tumor cells to some therapeutic agents, which might be explored for designing a proper therapeutic strategy. PMID- 20576603 TI - Matrix metalloproteinase 2 (MMP-2) degrades soluble vasculotropic amyloid-beta E22Q and L34V mutants, delaying their toxicity for human brain microvascular endothelial cells. AB - Patients carrying mutations within the amyloid-beta (Abeta) sequence develop severe early-onset cerebral amyloid angiopathy with some of the related variants manifesting primarily with hemorrhagic phenotypes. Matrix metalloproteases (MMPs) are typically associated with blood brain barrier disruption and hemorrhagic transformations after ischemic stroke. However, their contribution to cerebral amyloid angiopathy-related hemorrhage remains unclear. Human brain endothelial cells challenged with Abeta synthetic homologues containing mutations known to be associated in vivo with hemorrhagic manifestations (AbetaE22Q and AbetaL34V) showed enhanced production and activation of MMP-2, evaluated via Multiplex MMP antibody arrays, gel zymography, and Western blot, which in turn proteolytically cleaved in situ the Abeta peptides. Immunoprecipitation followed by mass spectrometry analysis highlighted the generation of specific C-terminal proteolytic fragments, in particular the accumulation of Abeta-(1-16), a result validated in vitro with recombinant MMP-2 and quantitatively evaluated using deuterium-labeled internal standards. Silencing MMP-2 gene expression resulted in reduced Abeta degradation and enhanced apoptosis. Secretion and activation of MMP 2 as well as susceptibility of the Abeta peptides to MMP-2 degradation were dependent on the peptide conformation, with fibrillar elements of AbetaE22Q exhibiting negligible effects. Our results indicate that MMP-2 release and activation differentially degrades Abeta species, delaying their toxicity for endothelial cells. However, taking into consideration MMP ability to degrade basement membrane components, these protective effects might also undesirably compromise blood brain barrier integrity and precipitate a hemorrhagic phenotype. PMID- 20576605 TI - Crotepoxide chemosensitizes tumor cells through inhibition of expression of proliferation, invasion, and angiogenic proteins linked to proinflammatory pathway. AB - Crotepoxide (a substituted cyclohexane diepoxide), isolated from Kaempferia pulchra (peacock ginger), although linked to antitumor and anti-inflammatory activities, the mechanism by which it exhibits these activities, is not yet understood. Because nuclear factor kappaB (NF-kappaB) plays a critical role in these signaling pathways, we investigated the effects of crotepoxide on NF-kappaB mediated cellular responses in human cancer cells. We found that crotepoxide potentiated tumor necrosis factor (TNF), and chemotherapeutic agents induced apoptosis and inhibited the expression of NF-kappaB-regulated gene products involved in anti-apoptosis (Bcl-2, Bcl-xL, IAP1,(2) MCl-1, survivin, and TRAF1), apoptosis (Bax, Bid), inflammation (COX-2), proliferation (cyclin D1 and c-myc), invasion (ICAM-1 and MMP-9), and angiogenesis (VEGF). We also found that crotepoxide inhibited both inducible and constitutive NF-kappaB activation. Crotepoxide inhibition of NF-kappaB was not inducer-specific; it inhibited NF kappaB activation induced by TNF, phorbol 12-myristate 13-acetate, lipopolysaccharide, and cigarette smoke. Crotepoxide suppression of NF-kappaB was not cell type-specific because NF-kappaB activation was inhibited in myeloid, leukemia, and epithelial cells. Furthermore, we found that crotepoxide inhibited TAK1 activation, which led to suppression of IkappaBalpha kinase, abrogation of IkappaBalpha phosphorylation and degradation, nuclear translocation of p65, and suppression of NF-kappaB-dependent reporter gene expression. Overall, our results indicate that crotepoxide sensitizes tumor cells to cytokines and chemotherapeutic agents through inhibition of NF-kappaB and NF-kappaB-regulated gene products, and this may provide the molecular basis for crotepoxide ability to suppress inflammation and carcinogenesis. PMID- 20576606 TI - Molecular characterization of a class I P450 electron transfer system from Novosphingobium aromaticivorans DSM12444. AB - Cytochrome P450 (CYP) enzymes of the CYP101 and CYP111 families from the oligotrophic bacterium Novosphingobium aromaticivorans DSM12444 are heme monooxygenases that receive electrons from NADH via Arx, a [2Fe-2S] ferredoxin, and ArR, a ferredoxin reductase. These systems show fast NADH turnovers (k(cat) = 39-91 s(-1)) that are efficiently coupled to product formation. The three dimensional structures of ArR, Arx, and CYP101D1, which form a physiological class I P450 electron transfer chain, have been resolved by x-ray crystallography. The general structural features of these proteins are similar to their counterparts in other class I systems such as putidaredoxin reductase (PdR), putidaredoxin (Pdx), and CYP101A1 of the camphor hydroxylase system from Pseudomonas putida, and adrenodoxin (Adx) of the mitochondrial steroidogenic CYP11 and CYP24A1 systems. However, significant differences in the proposed protein-protein interaction surfaces of the ferredoxin reductase, ferredoxin, and P450 enzyme are found. There are regions of positive charge on the likely interaction face of ArR and CYP101D1 and a corresponding negatively charged area on the surface of Arx. The [2Fe-2S] cluster binding loop in Arx also has a neutral, hydrophobic patch on the surface. These surface characteristics are more in common with those of Adx than Pdx. The observed structural features are consistent with the ionic strength dependence of the activity. PMID- 20576607 TI - Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity. AB - Heparanase activity is highly implicated in cell dissemination associated with tumor metastasis, angiogenesis, and inflammation. Heparanase expression is induced in many hematological and solid tumors, associated with poor prognosis. Heparanase homolog, termed heparanase 2 (Hpa2), was cloned based on sequence homology. Detailed characterization of Hpa2 at the biochemical, cellular, and clinical levels has not been so far reported, and its role in normal physiology and pathological disorders is obscure. We provide evidence that unlike heparanase, Hpa2 is not subjected to proteolytic processing and exhibits no enzymatic activity typical of heparanase. Notably, the full-length Hpa2c protein inhibits heparanase enzymatic activity, likely due to its high affinity to heparin and heparan sulfate and its ability to associate physically with heparanase. Hpa2 expression was markedly elevated in head and neck carcinoma patients, correlating with prolonged time to disease recurrence (follow-up to failure; p = 0.006) and inversely correlating with tumor cell dissemination to regional lymph nodes (N-stage; p = 0.03). Hpa2 appears to restrain tumor metastasis, likely by attenuating heparanase enzymatic activity, conferring a favorable outcome of head and neck cancer patients. PMID- 20576608 TI - MicroRNA-208 modulates BMP-2-stimulated mouse preosteoblast differentiation by directly targeting V-ets erythroblastosis virus E26 oncogene homolog 1. AB - MicroRNAs (miRs) represent a class of endogenous approximately 18-25 nucleotide RNAs that regulate gene expression through translational repression by binding to a target mRNA. These miRs regulate several biological functions, such as cell growth, cell differentiation, carcinogenesis, and so on. In a previous report, we have indicated that miR-141 and -200a act as preosteoblast differentiation modulators. In the present study, using microRNA array and in silico analyses, we found that miR-208 is closely involved in preosteoblast differentiation by partially regulating the expression of Ets1 (V-ets erythroblastosis virus E26 oncogene homolog 1), which transactivates osteopontin, runt-related transcription factor 2, parathyroid hormone-related protein, and type I procollagen. Furthermore, the enforced expression of mature miR-208 in murine preosteoblast in MC3T3-E1 cells or primary osteoblast cells remarkably attenuated BMP-2-induced preosteoblast differentiation. In addition, we determined that Ets1 is a target gene of miR-208 by using a sensor luciferase reporter assay. Taken together, these results suggest that the down-regulation of miR-208 in BMP-2-stimulated osteoblast differentiation is an important part of the regulatory machinery involved in early osteogenesis. PMID- 20576609 TI - Heparan sulfate domain organization and sulfation modulate FGF-induced cell signaling. AB - Heparan sulfates (HSs) modulate various developmental and homeostatic processes by binding to protein ligands. We have evaluated the structural characteristics of porcine HS in cellular signaling induced by basic fibroblast growth factor (FGF2), using CHO745 cells devoid of endogenous glycosaminoglycans as target. Markedly enhanced stimulation of cell signaling, measured as phosphorylation of ERK1/2 and protein kinase B, was only observed with the shortest HS chains isolated from liver, whereas the longer chains from either liver or intestine essentially prolonged duration of signals induced by FGF2 in the absence of polysaccharide. Structural analysis showed that contiguous sulfated domains were most abundant in the shortest HS chains and were more heavily sulfated in HS from liver than in HS from intestine. Moreover, the shortest chains from either source entered into ternary complexes with FGF2 and FGF receptor-1c more efficiently than the corresponding longer chains. In addition to authentic HSs, decasaccharide libraries generated by chemo-enzymatic modification of heparin were probed for effect on FGF2 signaling. Only the most highly sulfated decamers, previously found most efficient in ternary complex formation (Jastrebova, N., Vanwildemeersch, M., Rapraeger, A. C., Gimenez-Gallego, G., Lindahl, U., and Spillmann, D. (2006) J. Biol. Chem. 281, 26884-26892), promoted FGF2 cellular signaling as efficiently as short HS chains from liver. Together these results suggest that the effects of HS on FGF2 signaling are determined by both the structure of the highly sulfated domains and by the organization/availability of such domains within the HS chain. These findings underpin the need for regulation of HS biosynthesis in relation to control of growth factor-induced signaling pathways. PMID- 20576610 TI - Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. AB - Soluble oligomers of Abeta42 peptide are believed to play a major role in the pathogenesis of Alzheimer disease (AD). It was recently found that at least some of the neurotoxic effects of these oligomers may be mediated by specific binding to the prion protein, PrP(C), on the cell surface (Lauren, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., and Strittmatter, S. M. (2009) Nature 457, 1128 1132). Here we characterized the interaction between synthetic Abeta42 oligomers and the recombinant human prion protein (PrP) using two biophysical techniques: site-directed spin labeling and surface plasmon resonance. Our data indicate that this binding is highly specific for a particular conformation adopted by the peptide in soluble oligomeric species. The binding appears to be essentially identical for the Met(129) and Val(129) polymorphic forms of human PrP, suggesting that the role of PrP codon 129 polymorphism as a risk factor in AD is due to factors unrelated to the interaction with Abeta oligomers. It was also found that in addition to the previously identified approximately 95-110 segment, the second region of critical importance for the interaction with Abeta42 oligomers is a cluster of basic residues at the extreme N terminus of PrP (residues 23-27). The deletion of any of these segments results in a major loss of the binding function, indicating that these two regions likely act in concert to provide a high affinity binding site for Abeta42 oligomers. This insight may help explain the interplay between the postulated protective and pathogenic roles of PrP in AD and may contribute to the development of novel therapeutic strategies as well. PMID- 20576611 TI - Alternative ways to think about cellular internal ribosome entry. AB - Internal ribosome entry sites (IRESs) are specialized mRNA elements that allow recruitment of eukaryotic ribosomes to naturally uncapped mRNAs or to capped mRNAs under conditions in which cap-dependent translation is inhibited. Putative cellular IRESs have been proposed to play crucial roles in stress responses, development, apoptosis, cell cycle control, and neuronal function. However, most of the evidence for cellular IRES activity rests on bicistronic reporter assays, the reliability of which has been questioned. Here, the mechanisms underlying cap independent translation of cellular mRNAs and the contributions of such translation to cellular protein synthesis are discussed. I suggest that the division of cellular mRNAs into mutually exclusive categories of "cap-dependent" and "IRES-dependent" should be reconsidered and that the implications of cellular IRES activity need to be incorporated into our models of cap-dependent initiation. PMID- 20576612 TI - Control of translation initiation through integration of signals generated by hormones, nutrients, and exercise. AB - Control of translation initiation in a tissue of an intact mammalian organism is a highly complex process requiring the continuous integration of multiple positive and negative stimuli. For a tissue such as skeletal muscle, which has the capacity to undergo dramatic changes in size and protein content, translation initiation contributes importantly to the regulation of global rates of protein synthesis and is controlled by numerous stimuli, including those arising from nutrients and hormones in the circulating blood, as well as from contraction induced signaling within the tissue. Many of the pathways conveying signals generated by these stimuli converge on mTORC1, a serine-threonine protein kinase that has been termed the nutrient and energy sensor of the cell and that plays a prominent role in the regulation of cell growth. Control of translation initiation by mTORC1 is mediated through phosphorylation of downstream targets that modulate the binding of mRNA to the 43 S preinitiation complex. Control of translation initiation is also mediated through modulation of binding of initiator methionyl-tRNA to the 40 S ribosomal subunit. Together, modulation of these two regulatory steps in translation initiation accounts in large part for changes in protein synthesis in skeletal muscle produced by the integration of inputs from hormones, nutrients, and exercise. PMID- 20576613 TI - Role of mechanical stress-induced glutamate signaling-associated molecules in cytodifferentiation of periodontal ligament cells. AB - In this study, we analyzed the effects of tensile mechanical stress on the gene expression profile of in vitro-maintained human periodontal ligament (PDL) cells. A DNA chip analysis identified 17 up-regulated genes in human PDL cells under the mechanical stress, including HOMER1 (homer homolog 1) and GRIN3A (glutamate receptor ionotropic N-methyl-d-aspartate 3A), which are related to glutamate signaling. RT-PCR and real-time PCR analyses revealed that human PDL cells constitutively expressed glutamate signaling-associated genes and that mechanical stress increased the expression of these mRNAs, leading to release of glutamate from human PDL cells and intracellular glutamate signal transduction. Interestingly, exogenous glutamate increased the mRNAs of cytodifferentiation and mineralization-related genes as well as the ALP (alkaline phosphatase) activities during the cytodifferentiation of the PDL cells. On the other hand, the glutamate signaling inhibitors riluzole and (+)-MK801 maleate suppressed the alkaline phosphatase activities and mineralized nodule formation during the cytodifferentiation and mineralization. Riluzole inhibited the mechanical stress induced glutamate signaling-associated gene expressions in human PDL cells. Moreover, in situ hybridization analyses showed up-regulation of glutamate signaling-associated gene expressions at tension sites in the PDL under orthodontic tooth movement in a mouse model. The present data demonstrate that the glutamate signaling induced by mechanical stress positively regulates the cytodifferentiation and mineralization of PDL cells. PMID- 20576614 TI - MicroRNA-221 regulates chondrogenic differentiation through promoting proteosomal degradation of slug by targeting Mdm2. AB - MicroRNAs (miRNAs) are small RNAs that fulfill diverse functions by negatively regulating gene expression. Here, we investigated the involvement of miRNAs in the chondrogenic differentiation of chick limb mesenchymal cells and found that the expression of miR-221 increased upon chondrogenic inhibition. Blockade of miR 221 via peanut agglutinin-based antisense oligonucleotides reversed the chondro inhibitory actions of a JNK inhibitor on the proliferation and migration of chondrogenic progenitors as well as the formation of precartilage condensations. We determined that mdm2 is a relevant target of miR-221 during chondrogenesis. miR-221 was necessary and sufficient to down-regulate Mdm2 expression, and this down-modulation of Mdm2 by miR-221 prevented the degradation of (and consequently up-regulated) the Slug protein, which negatively regulates the proliferation of chondroprogenitors. These results indicate that miR-221 contributes to the regulation of cell proliferation by negatively regulating Mdm2 and thereby inhibiting Slug degradation during the chondrogenesis of chick limb mesenchymal cells. PMID- 20576615 TI - Defining specific lipid binding sites for a peripheral membrane protein in situ using subtesla field-cycling NMR. AB - Despite the profound physiological consequences associated with peripheral membrane protein localization, only a rudimentary understanding of the interactions of proteins with membrane surfaces exists because these questions are inaccessible by commonly used structural techniques. Here, we combine high resolution field-cycling (31)P NMR relaxation methods with spin-labeled proteins to delineate specific interactions of a bacterial phospholipase C with phospholipid vesicles. Unexpectedly, discrete binding sites for both a substrate analogue and a different phospholipid (phosphatidylcholine) known to activate the enzyme are observed. The lifetimes for the occupation of these sites (when the protein is anchored transiently to the membrane) are >1-2 micros (but <1 ms), which represents the first estimate of an off-rate for a lipid dissociating from a specific site on the protein and returning to the bilayer. Furthermore, analyses of the spin-label induced NMR relaxation corroborates the presence of a discrete tyrosine-rich phosphatidylcholine binding site whose location is consistent with that suggested by modeling studies. The methodology illustrated here may be extended to a wide range of peripheral membrane proteins. PMID- 20576616 TI - Deciphering the kinetic binding mechanism of dimeric ligands using a potent plasma-stable dimeric inhibitor of postsynaptic density protein-95 as an example. AB - Dimeric ligands can be potent inhibitors of protein-protein or enzyme-substrate interactions. They have increased affinity and specificity toward their targets due to their ability to bind two binding sites simultaneously and are therefore attractive in drug design. However, few studies have addressed the kinetic mechanism of interaction of such bivalent ligands. We have investigated the binding interaction of a recently identified potent plasma-stable dimeric pentapeptide and PDZ1-2 of postsynaptic density protein-95 (PSD-95) using protein engineering in combination with fluorescence polarization, isothermal titration calorimetry, and stopped-flow fluorimetry. We demonstrate that binding occurs via a two-step process, where an initial binding to either one of the two PDZ domains is followed by an intramolecular step, which produces the bidentate complex. We have determined all rate constants involved in the binding reaction and found evidence for a conformational transition of the complex. Our data demonstrate the importance of a slow dissociation for a successful dimeric ligand but also highlight the possibility of optimizing the intramolecular association rate. The results may therefore aid the design of dimeric inhibitors in general. PMID- 20576617 TI - Requirement for lamin B receptor and its regulation by importin {beta} and phosphorylation in nuclear envelope assembly during mitotic exit. AB - Lamin B receptor (LBR), a chromatin and lamin B-binding protein in the inner nuclear membrane, has been proposed to target the membrane precursor vesicles to chromatin mediated by importin beta during the nuclear envelope (NE) assembly. However, the mechanisms for the binding of LBR with importin beta and the membrane targeting by LBR in NE assembly remain largely unknown. In this report, we show that the amino acids (aa) 69-90 of LBR sequences are required to bind with importin beta at aa 45-462, and the binding is essential for the NE membrane precursor vesicle targeting to the chromatin during the NE assembly at the end of mitosis. We also show that this binding is cell cycle-regulated and dependent on the phosphorylation of LBR Ser-71 by p34(cdc2) kinase. RNAi knockdown of LBR causes the NE assembly failure and abnormal chromatin decondensation of the daughter cell nuclei, leading to the daughter cell death at early G(1) phase by apoptosis. Perturbation of the interaction of LBR with importin beta by deleting the LBR N-terminal spanning region or aa 69-73 also induces the NE assembly failure, the abnormal chromatin decondensation, and the daughter cell death. The first transmembrane domain of LBR promotes the NE production and expansion, because overexpressing this domain is sufficient to induce membrane overproduction of the NE. Thus, these results demonstrate that LBR targets the membrane precursor vesicles to chromatin by interacting with importin beta in a LBR phosphorylation-dependent manner during the NE assembly at the end of mitosis and that the first transmembrane domain of LBR promotes the LBR-bearing membrane production and the NE expansion in interphase. PMID- 20576619 TI - Effects of the biological clock gene Bmal1 on tumour growth and anti-cancer drug activity. AB - The Bmal1 gene plays a key role in controlling circadian rhythms. To better understand how the Bmal1 gene affects tumour growth and the response to anti cancer drugs, we examined the effect of knockdown of Bmal1 by RNAi both in vitro and in vivo. Down-regulation of Bmal1 gene expression accelerated cell proliferation in vitro and promoted tumour growth in mice. Suppressing Bmal1 expression in murine colon cancer cells (C26) and fibroblast cells (L929) decreased apoptosis induced by Etoposid, reduced the distribution of cells in the G2/M phases treated by Docetaxel and decreased DNA damage induced by Cisplatin. Loss of Bmal1 reduced the expression of per1, per2, per3, wee1 and p53. The expression of p21 and c-myc was also altered in certain cell lines. However, Bmal1 deficiency increased the protein levels of cdc2, cyclin B1, cyclin D1 and cyclin E. Wee1 and cyclin A expression was minimally altered. Thus, the circadian clock gene Bmal1 plays a role in regulating tumour cell apoptosis, cell-cycle progression and DNA damage response and in homoeostasis regulation. Down regulation of Bmal1 accelerates the development of tumours and may influence the response to anti-cancer drugs. PMID- 20576618 TI - Inactivation of Patched1 in the mouse limb has novel inhibitory effects on the chondrogenic program. AB - The bones of the vertebrate limb form by the process of endochondral ossification, whereby limb mesenchyme condenses to form an intermediate cartilage scaffold that is then replaced by bone. Although Indian hedgehog (IHH) is known to control hypertophic differentiation of chondrocytes during this process, the role of hedgehog signaling in the earlier stages of chondrogenesis is less clear. We have conditionally inactivated the hedgehog receptor Ptc1 in undifferentiated limb mesenchyme of the mouse limb using Prx1-Cre, thus inducing constitutively active ligand-independent hedgehog signaling. In addition to major patterning defects, we observed a marked disruption to the cartilage elements in the limbs of Prx1-Cre:Ptc1(c/c) embryos. Using an in vitro micromass culture system we show that this defect lies downstream of mesenchymal cell condensation and likely upstream of chondrocyte differentiation. Despite early increases in levels of chondrogenic genes, soon after mesenchymal condensation the stromal layer of Prx1 Cre:Ptc1(c/c)-derived micromass cultures is characterized by a loss of cell integrity, which is associated with increased cell death and a striking decrease in Alcian blue staining cartilage nodules. Furthermore, inhibition of the hedgehog pathway activation using cyclopamine was sufficient to essentially overcome this chondrogenic defect in both micromass and ex vivo explant assays of Prx1-Cre:Ptc1(c/c) limbs. These data demonstrate for the first time the inhibitory effect of cell autonomously activated hedgehog signaling on chondrogenesis, and stress the importance of PTC1 in maintaining strict control of signaling levels during this phase of skeletal development. PMID- 20576620 TI - Disulphide cross-linking between the stator and the bearing components in the bacterial flagellar motor. AB - The flagellar motor is composed of the stator and the rotor, and the interaction between the stator and the rotor at the cytoplasmic region is believed to produce mechanical force for the rotation of flagella. The periplasmic region of the stator has been proposed to play an important role in assembly around and incorporation into the motor. In this study, we provide evidence suggesting that the periplasmic region of the stator component MotB interacts with the P-ring component FlgI, which functions as a bearing for the rotor along with the L-ring protein FlgH, from a site-directed disulphide cross-linking approach. First, we prepared four FlgI and three MotB cysteine-substituted mutant proteins and co expressed them in various combinations in Escherichia coli. We detected cross linked combinations of FlgI G11C and MotB S248C when treated with the oxidant Cu phenanthroline or bismaleimide cross-linkers. Furthermore, we performed Cys scanning mutagenesis around these two residues and found additional combinations of cross-linked residues. Treatment with a protonophore CCCP significantly reduced the cross-linking efficiency between FlgI and MotB in flagellated cells, but not in non-flagellated cells. These results suggest a direct contact between MotB and FlgI upon assembly of the stator into a motor. PMID- 20576621 TI - In vitro evaluation of cellular responses induced by stable fullerene C60 medium dispersion. AB - Because of the expansion of the functionalities available for modification of fullerene C60 and its derivatives, their uses are increasing. However, the consequences of fullerene exposure to human health have not been fully studied. In vitro experiments are useful for risk assessment and for understanding potential applications. However, the insolubility of pristine C60 in water makes the in vitro evaluation of cellular responses difficult. To overcome this problem, we prepared a stable and uniform C60-medium dispersion for in vitro examinations. In addition, we examined the effect of the C60-medium dispersion on human keratinocyte HaCaT cells and human lung carcinoma A549 cells to understand the cellular responses induced by exposure to C60. Results indicated that exposure to C60 did not affect cell viability; neither apoptosis nor necrosis were induced, while cell proliferation was inhibited. Furthermore, intracellular oxidative stress was induced by C60 exposure in both HaCaT and A549 cells. Transmission electron microscopy indicated the cellular uptake of C60 aggregates. The results obtained from this study indicate that C60 has oxidative stress induction potential. Further examinations including in vivo studies are necessary for a more accurate evaluation of biological influences by C60. PMID- 20576622 TI - Cassis: detection of genomic rearrangement breakpoints. AB - SUMMARY: Genomes undergo large structural changes that alter their organization. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. Lemaitre et al. presented a new method to precisely delimit rearrangement breakpoints in a genome by comparison with the genome of a related species. Receiving as input a list of one2one orthologous genes found in the genomes of two species, the method builds a set of reliable and non-overlapping synteny blocks and refines the regions that are not contained into them. Through the alignment of each breakpoint sequence against its specific orthologous sequences in the other species, we can look for weak similarities inside the breakpoint, thus extending the synteny blocks and narrowing the breakpoints. The identification of the narrowed breakpoints relies on a segmentation algorithm and is statistically assessed. Here, we present the package Cassis that implements this method of precise detection of genomic rearrangement breakpoints. AVAILABILITY: Perl and R scripts are freely available for download at http://pbil.univ lyon1.fr/software/Cassis/. Documentation with methodological background, technical aspects, download and setup instructions, as well as examples of applications are available together with the package. The package was tested on Linux and Mac OS environments and is distributed under the GNU GPL License. PMID- 20576623 TI - Chromaligner: a web server for chromatogram alignment. AB - Chromaligner is a tool for chromatogram alignment to align retention time for chromatographic methods coupled to spectrophotometers such as high performance liquid chromatography and capillary electrophoresis for metabolomics works. Chromaligner resolves peak shifts by a constrained chromatogram alignment. For a collection of chromatograms and a set of defined peaks, Chromaligner aligns the chromatograms on defined peaks using correlation warping (COW). Chromaligner is faster than the original COW algorithm by k(2) times, where k is the number of defined peaks in a chromatogram. It also provides alignments based on known component peaks to reach the best results for further chemometric analysis. AVAILABILITY: Chromaligner is freely accessible at http://cmdd.csie.ntu.edu.tw/~chromaligner. PMID- 20576624 TI - EpiTOP--a proteochemometric tool for MHC class II binding prediction. AB - MOTIVATION: T-cell epitope identification is a critical immunoinformatic problem within vaccine design. To be an epitope, a peptide must bind an MHC protein. RESULTS: Here, we present EpiTOP, the first server predicting MHC class II binding based on proteochemometrics, a QSAR approach for ligands binding to several related proteins. EpiTOP uses a quantitative matrix to predict binding to 12 HLA-DRB1 alleles. It identifies 89% of known epitopes within the top 20% of predicted binders, reducing laboratory labour, materials and time by 80%. EpiTOP is easy to use, gives comprehensive quantitative predictions and will be expanded and updated with new quantitative matrices over time. AVAILABILITY: EpiTOP is freely accessible at http://www.pharmfac.net/EpiTOP. PMID- 20576625 TI - A probabilistic framework for aligning paired-end RNA-seq data. AB - MOTIVATION: The RNA-seq paired-end read (PER) protocol samples transcript fragments longer than the sequencing capability of today's technology by sequencing just the two ends of each fragment. Deep sampling of the transcriptome using the PER protocol presents the opportunity to reconstruct the unsequenced portion of each transcript fragment using end reads from overlapping PERs, guided by the expected length of the fragment. METHODS: A probabilistic framework is described to predict the alignment to the genome of all PER transcript fragments in a PER dataset. Starting from possible exonic and spliced alignments of all end reads, our method constructs potential splicing paths connecting paired ends. An expectation maximization method assigns likelihood values to all splice junctions and assigns the most probable alignment for each transcript fragment. RESULTS: The method was applied to 2 x 35 bp PER datasets from cancer cell lines MCF-7 and SUM-102. PER fragment alignment increased the coverage 3-fold compared to the alignment of the end reads alone, and increased the accuracy of splice detection. The accuracy of the expectation maximization (EM) algorithm in the presence of alternative paths in the splice graph was validated by qRT-PCR experiments on eight exon skipping alternative splicing events. PER fragment alignment with long range splicing confirmed 8 out of 10 fusion events identified in the MCF-7 cell line in an earlier study by (Maher et al., 2009). AVAILABILITY: Software available at http://www.netlab.uky.edu/p/bioinfo/MapSplice/PER. PMID- 20576626 TI - Single feature polymorphism detection using recombinant inbred line microarray expression data. AB - MOTIVATION: The Affymetrix GeneChip microarray is currently providing a high density and economical platform for discovery of genetic polymorphisms. Microarray data for single feature polymorphism (SFP) detection in recombinant inbred lines (RILs) can capitalize on the high level of replication available for each locus in the RIL population. It was suggested that the binding affinities from all of the RILs would form a multimodal distribution for a SFP. This motivated us to estimate the binding affinities from the robust multi-array analysis (RMA) method and formulate the SFP detection problem as a hypothesis testing problem, i.e. testing whether the underlying distribution of the estimated binding affinity (EBA) values of a probe is unimodal or multimodal. RESULTS: We developed a bootstrap-based hypothesis testing procedure using the 'dip' statistic. Our simulation studies show that the proposed procedure can reach satisfactory detection power with false discovery rate controlled at a desired level and is robust to the unimodal distribution assumption, which facilitates wide application of the proposed procedure. Our analysis of the real data identified more than four times the SFPs compared to the previous studies, covering 96% of their findings. The constructed genetic map using the SFP markers predicted from our procedure shows over 99% concordance of the genetic orders of these markers with their known physical locations on the genome sequence. AVAILABILITY: The R package 'dipSFP' can be downloaded from http://sites.google.com/a/bioinformatics.ucr.edu/xinping-cui/home/software. PMID- 20576627 TI - MSAProbs: multiple sequence alignment based on pair hidden Markov models and partition function posterior probabilities. AB - MOTIVATION: Multiple sequence alignment is of central importance to bioinformatics and computational biology. Although a large number of algorithms for computing a multiple sequence alignment have been designed, the efficient computation of highly accurate multiple alignments is still a challenge. RESULTS: We present MSAProbs, a new and practical multiple alignment algorithm for protein sequences. The design of MSAProbs is based on a combination of pair hidden Markov models and partition functions to calculate posterior probabilities. Furthermore, two critical bioinformatics techniques, namely weighted probabilistic consistency transformation and weighted profile-profile alignment, are incorporated to improve alignment accuracy. Assessed using the popular benchmarks: BAliBASE, PREFAB, SABmark and OXBENCH, MSAProbs achieves statistically significant accuracy improvements over the existing top performing aligners, including ClustalW, MAFFT, MUSCLE, ProbCons and Probalign. Furthermore, MSAProbs is optimized for multi-core CPUs by employing a multi-threaded design, leading to a competitive execution time compared to other aligners. AVAILABILITY: The source code of MSAProbs, written in C++, is freely and publicly available from http://msaprobs.sourceforge.net. PMID- 20576628 TI - Television viewing time independently predicts all-cause and cardiovascular mortality: the EPIC Norfolk study. AB - BACKGROUND: Television viewing (TV), a highly prevalent behaviour, is associated with higher cardiovascular risk independently of physical activity. The relationship with mortality, however, is relatively unknown. METHODS: We examined the prospective relationship between TV time and all-cause, cardiovascular and cancer mortality in a population-based cohort [The European Prospective Investigation into Cancer and Nutrition (EPIC), Norfolk] of 13 197 men and women {age [SD (standard deviation)]: 61.5 +/- 9.0 years}. Participants were free from stroke, myocardial infarction and cancer at baseline in 1998-2000 and were followed up for death ascertainment until 2009 (9.5 +/- 1.6 years). TV time, total physical activity energy expenditure (PAEE), education level, smoking status, alcohol consumption, anti-hypertensive and lipid-lowering medication use, participant and family history of disease and total energy intake were self reported; height and weight were measured by standardized procedures. Hazard ratios (HRs) [95% confidence interval (CI)] for mortality were estimated per 1 h/day increase in TV. RESULTS: Each 1-h/day increase in TV time was associated with increased hazard of all-cause (HR = 1.04, 95% CI = 1.01-1.09; 1270 deaths) and cardiovascular (HR = 1.07, 95% CI = 1.01-1.15; 373 deaths), but not cancer mortality (HR = 1.04, 95% CI = 0.98-1.10; 570 deaths). This was independent of gender, age, education, smoking, alcohol, medication, diabetes history, family history of cardiovascular disease and cancer, body mass index (BMI) and PAEE. They were similar when stratified by gender, age, education, BMI and PAEE. The population-attributable fraction for all-cause mortality comparing the highest TV tertile (>3.6 h/day) with the lowest (<2.5 h/day) was 5.4%. CONCLUSIONS: These findings suggest that public health recommendations should consider advising a reduction in TV time, a predominant leisure activity in modern society, in addition to advocating physical activity. PMID- 20576630 TI - Cardiovascular MRI in patients with ischaemic heart disease: from science to practice? PMID- 20576629 TI - VH/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody. AB - Thrombopoietin receptor agonist humanized VB22B single-chain diabody (hVB22B (scFv)(2)) was found to be expressed as a mixture of two conformational isomers, a single-chain diabody form and a bivalent scFv form, which had different V(H)/V(L) (variable region of the heavy chain/light chain) association patterns. The single-chain diabody form showed significantly higher biological activity than the bivalent scFv form and, when incubated at elevated temperatures, exhibited novel isomerization to the inactive bivalent scFv form. Therefore, therapeutic development of hVB22B (scFv)(2) would require separation of the purified single-chain diabody form from the mixture of the two conformational isomers and also inhibition of isomerization into an inactive bivalent scFv form during storage. Novel V(H)/V(L) interface engineering in hVB22 (scFv)(2), in which hydrogen bonding between H39 and L38 was substituted with electrostatic interaction to enhance the desired V(H)/V(L) association and inhibit the undesired V(H)/V(L) association, enabled selective expression of the desired conformational isomer without any reduction in biological activity or thermal stability. Moreover, V(H)/V(L) interface-engineered hVB22 (scFv)(2) was completely resistant to isomerization. Because the hydrogen bonding interaction between H39 and L38 and the surrounding residues are highly conserved in human antibody sequences, V(H)/V(L) interface engineering could be generally applied to various (scFv)(2) molecules for selective expression and inhibition of the isomerization of conformational isomers. PMID- 20576631 TI - Norepinephrine and ephedrine do not counteract the increase in cutaneous microcirculation induced by spinal anaesthesia. AB - BACKGROUND: Neuraxial anaesthesia improves tissue perfusion and tissue oxygen tension. Vasodilation induced by this technique may result in hypotension requiring the administration of vasoactive drugs. The use of peripheral vasoconstrictors might counteract the improved tissue perfusion and its potentially beneficial effects. We therefore investigated the effect of i.v. norepinephrine and ephedrine on skin perfusion using laser-Doppler flowmetry (LDF) in patients during spinal anaesthesia. METHODS: Skin blood flow expressed in perfusion units (PU) provided by LDF was measured simultaneously at the foot and the manubrium levels in 44 patients during spinal anaesthesia with a sensory level below T5. Norepinephrine infusion was then titrated to normalize mean arterial pressure (MAP) in 23 patients (Group NOR). Ephedrine (max. 10 mg) was administered in 21 patients (Group EPH). Changes in relative PU were compared between the two sites of measurements in each group during drug administration. The same doses of norepinephrine were assessed in 11 normal volunteers to assure comparable vasoreactivity at the foot and manubrium levels. RESULTS: Spinal anaesthesia resulted in a 10% decrease in MAP (P<0.001), an increase in relative PU values at the foot level (P<0.001), and a decrease at the sternum level (P<0.05). Norepinephrine and ephedrine produced a significant increase in relative PU values at the foot level when compared with the sternum level (NOR: P=0.02; EPH: P=0.0035). In volunteers, norepinephrine decreased cutaneous perfusion similarly at the manubrium and foot levels. CONCLUSIONS: Improved skin perfusion induced by spinal anaesthesia was not counteracted by the use of norepinephrine or ephedrine. PMID- 20576632 TI - Postoperative residual curarization from intermediate-acting neuromuscular blocking agents delays recovery room discharge. AB - BACKGROUND: Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that postoperative T4/T1 <0.9 increases PACU length of stay. METHODS: At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation current: 30 mA) in 246 consecutive patients. The potential consequences of PORC induced increases in PACU length of stay on PACU throughput were estimated by application of a validated queuing model taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU plus patients recovering in operation theatre waiting for PACU beds. RESULTS: PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1 <0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed discharge significantly increases the chances of patients having to wait to enter the PACU. The presence of PORC is estimated to be associated with significant delays in recovery room admission. CONCLUSIONS: PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In our system, PORC increases the chances of patients having to wait to enter the PACU. PMID- 20576633 TI - Effects of different inspired oxygen fractions on lipid peroxidation during general anaesthesia for elective Caesarean section. AB - BACKGROUND: During general anaesthesia (GA) for Caesarean section (CS), fetal oxygenation is increased by administering an inspired oxygen fraction (Fi(o(2))) of 1.0. However, it is unclear whether such high Fi(o(2)) will increase oxygen free radical activity. METHODS: We randomized 39 ASA I-II parturients undergoing elective CS under GA to receive 30% (Gp 30), 50% (Gp 50), or 100% (Gp 100) oxygen with nitrous oxide and sevoflurane adjusted to provide equivalent minimum alveolar concentration. Baseline maternal arterial blood before preoxygenation and maternal arterial, umbilical arterial and venous blood at delivery were sampled for assays of the by-product of lipid peroxidation, isoprostane, and for measurement of blood gases and oxygen content. RESULTS: Maternal and umbilical isoprostane concentrations were similar among the three groups at delivery, despite significantly increased maternal and fetal oxygenation in Gp 100. However, paired comparisons of maternal delivery vs baseline concentration of isoprostane showed an increase at delivery for all groups [Gp 30: mean 342 (sd 210) vs 154 (65) pg ml(-1), P=0.016; Gp 50: 284 (129) vs 156 (79) pg ml(-1), P=0.009; Gp 100: 332 (126) vs 158 (68) pg ml(-1), P<0.001]. The magnitude of increase was similar in all three groups and independent of the Fi(o(2)) or duration after induction. CONCLUSIONS: GA for CS is associated with a marked increase in free radical activity in the mother and baby. The mechanism is unclear but it is independent of the inspired oxygen in the anaesthetic mixture. Therefore, when 100% oxygen is administered with sevoflurane for GA, fetal oxygenation can be increased, without inducing an increase in lipid peroxidation. PMID- 20576634 TI - Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model. AB - BACKGROUND: Abnormal placentation is a potential mechanism to explain the increased incidence of low birthweight observed after IVF. This study evaluates, in a mouse model, whether the method of conception and embryo transfer affect placentation and fetal development. METHODS: IVF blastocysts (CF1 x B6D2F1/J) were cultured in Whitten's medium (IVF(WM), n = 55) or K modified simplex optimized medium with amino acids (IVF(KAA), n = 56). Embryos were transferred to the uteri of pseudo-pregnant recipients. Two control groups were created: unmanipulated embryos produced by natural mating (in vivo group, n = 64) and embryos produced by natural mating that were flushed from uterus and immediately transferred to pseudo-pregnant recipients (flushed blastocysts, FB group, n = 57). At gestation age 12.5 days, implantation sites were collected and fixed; fetuses and placentas were weighed and their developmental stage (DS) evaluated. Placental areas and vascular volume fractions were calculated; parametric statistics were applied as appropriate. RESULTS: IVF fetuses showed a modest but significant delay in development compared with FB mice (P < 0.05). In addition, IVF conceptuses were consistently smaller than FB (P < 0.05). Importantly, these differences persisted when analyzing fetuses of similar DS. The placenta/fetus ratio was larger in the IVF group (IVF(WM) 0.95; IVF(KAA) = 0.90) than the FB group (0.72) (P < 0.05 for all comparisons). Gross morphology of the placenta and ratio labyrinth/fetal area were equivalent in the IVF and FB groups, as were percentage of fetal blood vessels, maternal blood spaces and trophoblastic components. CONCLUSIONS: In vitro embryo culture affects fetal and placental development; this could explain the lower birthweight in IVF offspring. PMID- 20576635 TI - OCT4 expression in human uterine myometrial stem/progenitor cells. AB - BACKGROUND: The transcription factor, octamer-binding transcription factor 4 (OCT4)/POU5F1, is expressed in embryonic stem cells, germ cells and some types of adult stem cells. Human OCT4 encodes two isoforms, OCT4A and OCT4B. While OCT4A plays a crucial role in the maintenance of stem cell properties, including pluripotency, whereas OCT4B does not. We previously reported that human myometrium contains side population cells (myoSP) with a Hoechst 33 342 low fluorescent profile. These cells exhibit phenotypic and functional characteristics of myometrial stem cells. The objective of this study was to investigate the comparative expression of OCT4 in the stem/progenitor cell population of the human myometrium. METHODS: Human myometrial tissue samples were collected from 18 consenting patients who underwent hysterectomy because of benign gynecological diseases. The resultant isolated or cultured myometrial cells and isolated myoSP were subjected to semi-quantitative and real-time RT-PCR analyses, immunoblot analyses and immunohistochemistry. RESULTS: RT-PCR and immunoblot analyses revealed that OCT4 mRNA and OCT4 protein were detectable in some (but not all) myometrial samples. Immunohistochemistry showed that OCT4 protein was confined to the nuclei of relatively few cells in myometrial tissues expressing OCT4 mRNA. OCT4 and OCT4A transcripts, but not those of OCT4B, were more abundant in myoSP than in non-myoSP, as determined by real-time and semi quantitative RT-PCR analyses. CONCLUSIONS: Relatively few myometrial cells express OCT4 protein. OCT4 mRNA, in particular OCT4A mRNA, is up-regulated in myoSP that have been reported to exhibit stem cell-like properties. Taken together, the present results indicate that the myoSP population is enriched in OCT4 mRNA. PMID- 20576636 TI - Cytokine and hormonal profile in serum samples of patients undergoing controlled ovarian stimulation: interleukin-1beta predicts ongoing pregnancy. AB - BACKGROUND: Changes in the endometrium are not regulated exclusively by ovarian hormones; the immune system has also been implicated in normal endometrial function, similar to processes taking place during inflammatory and reparative path. Many cytokines are crucially important for reproductive processes, and the role of cytokines in the female reproductive system function has been broadly investigated during controlled ovarian stimulation (COS) for IVF attempts. The aim of this study was to evaluate the levels of serum cytokines and hormones, and the clinical outcomes of women who underwent COS and ICSI procedures. METHODS: The study prospectively included 96 patients (aged 22-43 years, unexplained or male infertility, n = 61; female infertility factors, n = 35) who underwent ICSI cycles. Serum levels of interleukin (IL-8, IL-6, IL-1beta, IL-10, IL-12), tumour necrosis factor and leukaemia-inhibitory factor (LIF) and the hormones FSH, estradiol, progesterone, anti-Mullerian hormone and Inhibin-B were measured on the day of oocyte retrieval. RESULTS: The ongoing pregnancy rate was 25.3%. The presence of serum IL-1beta positively affected the implantation rate (P = 0.004) and increased the chance of becoming pregnant by 15 fold. Furthermore, the percentage of patients with detectable serum IL-1beta levels who conceived (62.5%) was higher than those who failed to conceive (37.5%; P = 0.019). The LIF was undetectable in all serum samples, and no other factors influenced the clinical outcomes of patients undergoing ICSI cycles. CONCLUSIONS: Our findings revealed that detectable serum levels of IL-1beta on the day of oocyte retrieval in patients undergoing COS and ICSI are predictive of successful implantation and ongoing pregnancy. PMID- 20576637 TI - Drug resistance is widespread among children who receive long-term antiretroviral treatment at a rural Tanzanian hospital. AB - OBJECTIVES: To assess long-term virological efficacy and the emergence of drug resistance in children who receive antiretroviral treatment (ART) in rural Tanzania. PATIENTS AND METHODS: Haydom Lutheran Hospital has provided ART to HIV infected individuals since 2003. From February through May 2009, a cross sectional virological efficacy survey was conducted among children (<15 years) who had completed >or=6 months of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Genotypic resistance was determined in those with a viral load of >200 copies/mL. RESULTS: Virological response was measured in 19 of 23 eligible children; 8 of 19 were girls and median age at ART initiation was 5 years (range 2-14 years). Median duration of ART at the time of the survey was 40 months (range 11-61 months). Only 8 children were virologically suppressed (50% harboured drug resistance. Results for children were markedly poorer than for adults attending the same programme, underscoring the need for improved treatment strategies for children in resource-limited settings. PMID- 20576638 TI - Long-term stability of temocillin in elastomeric pumps for outpatient antibiotic therapy in cystic fibrosis patients. PMID- 20576639 TI - Correlation between reduced susceptibility to disinfectants and multidrug resistance among clinical isolates of Acinetobacter species. AB - BACKGROUND: The aim of this study was to investigate the susceptibility profiles to disinfectants and antimicrobial agents of 283 non-repetitive Acinetobacter clinical isolates obtained in 97 Japanese hospitals in March 2002. METHODS: Susceptibility profiles of the above isolates to four disinfectants, six antimicrobial agents and two dyes were investigated. MICs were measured by the agar dilution method recommended by the CLSI (formerly NCCLS). MBC measurements and time-kill assays were performed using a slightly modified quantitative suspension test based on the European Standard EN 1040. RESULTS: No evident resistance to disinfectants was seen among the 283 strains of Acinetobacter spp. isolated in 2002, but the MIC(90)s of chlorhexidine gluconate, benzalkonium chloride and alkyldiaminoethylglycine hydrochloride were 50, 50 and 400 mg/L, respectively. Interestingly, the MICs of alkyldiaminoethylglycine hydrochloride and benzethonium chloride for four and three clinical isolates, respectively, reached 800 mg/L (approximately half the in-use concentration). The MBCs for the 28 disinfectant reduced susceptibility (DRS) isolates, for which the MICs of at least one of the four disinfectants tested were higher than the MIC(90), were comparable to those for susceptible isolates, in general; however, significant differences (P < 0.01) were observed between disinfectant-susceptible and DRS isolates in the time-kill assays of chlorhexidine gluconate, benzalkonium chloride and benzethonium chloride. Furthermore, DRS isolates tended to demonstrate multiresistance profiles to ceftazidime, ciprofloxacin and amikacin (P < 0.05). CONCLUSIONS: Since several Acinetobacter clinical isolates have developed augmented resistance to multiple antimicrobials and disinfectants, it is worth checking the susceptibility to disinfectants if multidrug-resistant Acinetobacter spp. are recurrently isolated clinically. PMID- 20576640 TI - A province-level risk factor analysis of fluoroquinolone consumption patterns in Canada (2000-06). AB - OBJECTIVES: To assess potential risk factors among socioeconomic variables and the rate of influenza for the use of different fluoroquinolone antimicrobials in Canada, and to evaluate modelling fluoroquinolone-use data by two different outcome measures. METHODS: Fluoroquinolone use was described monthly from 2000 to 2006 by two outcome measurements: defined daily doses and prescription counts. Multivariable linear and negative binomial models were produced with socioeconomic and influenza rate data. RESULTS: Significant socioeconomic predictors varied among the individual fluoroquinolone models, which may reflect the range of infections that are treated with fluoroquinolones. However, socioeconomic variables within the ciprofloxacin and levofloxacin models were similar, and indicated that use was highest in advantaged populations, depending on the measures being assessed. The rate of influenza was a significant predictor within models describing levofloxacin use and the defined daily dose model for ciprofloxacin use, after accounting for season. Influenza significantly interacted with the education variable in the levofloxacin defined daily dose model. CONCLUSIONS: Significant associations between levofloxacin use and influenza rates, after accounting for season, may suggest that levofloxacin was used to treat secondary bacterial infections or was prescribed inappropriately for seasonal viral respiratory tract infections. Yearly patterns of ciprofloxacin use show that prescribing practices changed; more ciprofloxacin prescriptions were dispensed towards the end of the study period, but for smaller doses or shorter treatment times. Associations with socioeconomic variables suggest that the fluoroquinolones ciprofloxacin and levofloxacin were more likely to be used in advantaged populations, probably due to the high cost of fluoroquinolone antimicrobials in comparison to the penicillin and macrolide groups. PMID- 20576641 TI - Activity of antiandrogens against juvenile and adult Schistosoma mansoni in mice. AB - OBJECTIVES: The antischistosomal properties of the marketed antiandrogens bicalutamide, flutamide, nilutamide and cyproterone acetate were studied both in vivo and in vitro. METHODS: Schistosoma mansoni-infected mice were treated orally with 50-400 mg/kg of the antiandrogens 3 and 7 weeks post-infection. In addition, three drug combinations of nilutamide and praziquantel (200/100, 100/100 and 100/50 mg/kg) were administered to mice harbouring adult S. mansoni. Drug effects were also monitored in vitro following exposure to antiandrogen concentrations of 1, 10 and 100 microg/mL. RESULTS: Low total worm burden reductions (5%-37%) and low to moderate female worm burden reductions (13%-75%) were achieved with the antiandrogens in the S. mansoni juvenile infection model. While flutamide and cyproterone acetate lacked activity against adult S. mansoni in vivo, low to moderate total and female worm burden reductions (0%-47%) were observed with bicalutamide. The highest total and female worm burden reductions (85% and 71%, respectively) (P < 0.001) were documented following a single 400 mg/kg dose of nilutamide. Statistically significant total (91%) and female (85%) worm burden reductions were achieved with the combination of nilutamide (200 mg/kg) and praziquantel (100 mg/kg). Schistosomes incubated with 100 microg/mL cyproterone acetate in vitro died after 15 h. Incubation with bicalutamide, nilutamide and flutamide at 100 microg/mL resulted in decreased movement of S. mansoni adults. CONCLUSIONS: Our data indicate that the hydantoin derivative nilutamide has interesting antischistosomal properties, confirming previous results of schistosomicidal activities of this drug class. PMID- 20576642 TI - Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population. AB - OBJECTIVE: While many studies have shown an association between the gene coding for adiponectin (ADIPOQ) and adiponectin levels, much more controversy surrounds its association with metabolic traits such as insulin resistance, obesity and type 2 diabetes. Furthermore, very few studies have looked into the relations between ADIPOQ variants and risk of cardiovascular disease. The present study assessed the influence of four common ADIPOQ Single Nucleotide Polymorphisms (SNPs), rs17300539 (-11391G->A), rs266729 (-11377C->G), rs2241766 (+45T->G) and rs1501299 (+276G->T) on the risk of myocardial infarction and type 2 diabetes. METHODS: and RESULTS: A large genetic association case-control study was conducted in 2008 Italians, including patients with myocardial infarction, type 2 diabetes, or both, and a reference group of healthy controls. Homozygotes TT for the rs1501299 (+276) had half the risk of either myocardial infarction alone or in association with type 2 diabetes when compared to the carriers of the G allele (OR = 0.58, p =0.01, and OR = 0.55, p =0.006 respectively). SNPs rs17300539 ( 11391), rs266729 (-11377) and rs2241766 (+45) showed no significant association with any of the three case groups. CONCLUSIONS: These results suggest that homozygotes TT for the adiponectin polymorphism rs1501299 (+276) are protected from the risk of myocardial infarction. PMID- 20576643 TI - Systemic miRNA-195 differentiates breast cancer from other malignancies and is a potential biomarker for detecting noninvasive and early stage disease. AB - PURPOSE: The potential of microRNAs (miRNAs) as novel tumor markers has been the focus of recent scrutiny because of their tissue specificity, stability, and association with clinicopathological parameters. Data have emerged documenting altered systemic miRNA expression across a spectrum of cancers; however, it remains uncertain as to whether circulating miRNAs are tumor specific. Our aim was to assess a panel of cancer-associated miRNAs in the circulation of patients with various malignancies, to determine whether these "oncomirs" were tumor specific, and thus to establish whether systemic miRNA analysis has utility in cancer diagnosis. PATIENTS AND METHODS: Whole blood samples were prospectively collected from preoperative cancer patients (breast, prostate, colon, and renal cancer and melanoma; n = 163) and healthy age- and sex-matched controls (n = 63). Total RNA was isolated, and a panel of seven miRNAs was quantified by real-time quantitative polymerase chain reaction in each sample. RESULTS: Differential expression of the general oncomirs let 7a, miR-10b, and miR-155, was observed in the majority of cancer patients in a nonspecific manner. Significantly, elevated circulating miR-195 was found to be breast cancer specific and could differentiate breast cancer from other cancers and from controls with a sensitivity of 88% at a specificity of 91%. A combination of three circulating miRNAs, including miR-195, further enhanced the discriminative power of this test for breast cancer to 94%. CONCLUSION: These findings suggest that individual cancers display specific systemic miRNA profiles, which could aid in discriminating among cancer types. This finding is of notable clinical consequence because it illustrates the potential of systemic miRNAs as sensitive, specific, noninvasive cancer biomarkers. PMID- 20576644 TI - Underuse of anthracyclines in women with HER-2+ advanced breast cancer. AB - Anthracyclines are among the most active drugs in breast cancer. Because of excessive cardiotoxicity, their use in combination with trastuzumab has been discouraged in patients with human epidermal growth factor receptor (HER)-2(+) metastatic breast cancer. We sought to describe how this treatment paradigm influenced the use of anthracyclines in this patient setting. We analyzed a multi institutional database containing the treatment history of 450 patients who received at least one trastuzumab-based regimen for HER-2(+) metastatic breast cancer. Patients were considered eligible for anthracyclines for metastatic disease if they were never exposed (NE) or had been previously exposed (PE) to an anthracycline in the neoadjuvant or adjuvant setting and had relapsed after 12 months from the last dose. We then assessed the use of anthracycline-based therapy after failure with the first trastuzumab-based regimen in eligible patients. Three-hundred twenty-one patients were considered eligible for anthracyclines. In total, 190 eligible patients developing disease progression during the initial trastuzumab-based therapy were analyzed. An anthracycline was administered as first salvage treatment in 14 NE and two PE patients. Another 15 NE and nine PE patients received an anthracycline as a further line of therapy. Of 119 eligible patients who died from breast cancer, only 30 received an anthracycline for metastatic disease. In conclusion, despite the fact that two thirds of the patients receiving trastuzumab-based therapy for HER-2 metastatic breast cancer are eligible for anthracyclines, these drugs are infrequently used nowadays to treat trastuzumab-refractory disease. A role for these compounds should be redefined in this patient subset. PMID- 20576645 TI - Co-Occurrence of ADHD and high IQ: a case series empirical study. AB - OBJECTIVE: The validity of a diagnosis of ADHD in children with a high intelligence quotient (IQ) remains controversial. Using a multidisciplinary approach, rigorous diagnostic criteria, and worldwide-validated psychometric instruments, we identified a group of children attending public schools in southern Brazil for co-occurrence of high IQ and ADHD. METHOD: Students attending public schools, in the first to fifth grades, were referred to our Research Center for behavioral and/or learning difficulties. These children completed clinical, psychiatric, psychological, and pedagogical evaluations for assessment of IQ, ADHD, learning, and other emotional or behavioral disorders. RESULTS: Fifteen of the participants were identified to have a full-scale IQ >= 120. Data show that 10 of these high-IQ children met the DSM-IV criteria diagnosis for ADHD combined type, 5 met criteria for current oppositional-defiant disorder, 2 had current major depression, and 2 had a learning disorder. Here we present the results as a case series. CONCLUSION: Our data support the hypothesis that ADHD is a valid diagnosis in children with high IQs. PMID- 20576646 TI - ADHD in the college student: is anyone else worried? AB - The illegal, non-prescriptive use of prescription stimulants appears to be growing among college students. Recent analyses using DSM-IV criteria suggest that this group of misusers may actually represent cases of undiagnosed ADHD. Such analyses, however, are limited by a diagnostic system that is neither contextural nor dimensional. The ADHD symptoms of the newly diagnosed college student may be highly context and time specific and represent a normal response to temporarily increased demands on intellect and motivation. Diagnosing college students who are misusing stimulants with ADHD runs the risk of further trivializing the ADHD diagnosis. Also from a historical perspective, legitimizing the use of prescription stimulants in this age group may unintentionally only further increase the likelihood of a greater prescription stimulant abuse epidemic. PMID- 20576647 TI - Stimulant medication and prefrontal functional connectivity during working memory in ADHD: a preliminary report. AB - OBJECTIVE: Recent theoretical and empirical work suggests that while unmedicated, children with ADHD have a deficit in subcortical processing that leads to greater and more varied prefrontal cortical (PFC) activation, compared to (a) age-matched control participants and (b) their own brain activity while on stimulant medication. This pattern has been described elsewhere as inefficient. METHOD: Functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used during a working memory task for five female adolescents with ADHD, aged 11 to 17 years, both on and off their usual dose of stimulant medication. RESULTS: On medication, adolescents with ADHD demonstrated less PFC activation and less functional connectivity between frontal and subcortical regions compared to off medication. CONCLUSIONS: Because of the small sample size, results are presented as preliminary findings which await replication in a larger sample. However, these findings lend support to the idea that remediation of inefficiencies in PFC function for individuals with ADHD by stimulant medication may be related, in part, to frontal-subcortical connectivity. PMID- 20576648 TI - Age-related changes in scavenger receptor-mediated endocytosis in rat liver sinusoidal endothelial cells. AB - Liver sinusoidal endothelial cells (LSECs) play an essential role in systemic waste clearance by effective endocytosis of blood-borne waste macromolecules. We aimed to study LSECs' scavenger function during aging, and whether age-related morphological changes (eg, defenestration) affect this function, in F344/BN F1 rats. Endocytosis of the scavenger receptor ligand formaldehyde-treated serum albumin was significantly reduced in LSECs from old rats. Ligand degradation, LSEC protein expression of the major scavenger receptors for formaldehyde-treated serum albumin endocytosis, stabilin-1 and stabilin-2, and their staining patterns along liver sinusoids, was similar at young and old age, suggesting that other parts of the endocytic machinery are affected by aging. Formaldehyde-treated serum albumin uptake per cell, and cell porosity evaluated by electron microscopy, was not correlated, indicating that LSEC defenestration is not linked to impaired endocytosis. We report a significantly reduced LSEC endocytic capacity at old age, which may be especially important in situations with increased circulatory waste loads. PMID- 20576650 TI - Adipokine profile and insulin sensitivity in formerly obese women subjected to bariatric surgery or diet-induced long-term caloric restriction. AB - To better understand the contribution of the fat mass to the effects of long-term caloric restriction in humans, we compared adipokine profile and insulin sensitivity in long-term calorically restricted formerly obese women (CRW) subjected to different interventions, bariatric surgery, or reducing diet, with age- and BMI-matched obese (OW) and normal-weight women (NW) eating ad libitum. Our key findings are that despite a considerably stronger weight loss induced by bariatric surgery, both long-term caloric restriction interventions improved insulin sensitivity to the same degree and led to significantly lower retinol binding protein-4 and interleukin-6 serum levels than in OW, suggesting that lowering of these two adipokines contributes to the improved insulin sensitivity. Moreover, serum leptin was considerably lower in CRW than in OW as well as in NW, suggesting that CRW develop hypoleptinemia. PMID- 20576651 TI - Skin sparing modified Ravitch repair for pectus excavatum. AB - A 26-year-old woman presented with severe exercise intolerance and pectus excavatum. She had significant sternal depression from ribs 2-6 with rotation to the right and a concomitant saucer deformity of the right anterior chest wall. The patient was evaluated and offered both the Ravitch and the Nuss repair. She chose the Ravitch repair but still had cosmetic concerns. A skin sparing modified Ravitch repair was performed through bilateral infra-mammary incisions with excellent cosmetic results. PMID- 20576652 TI - Azygous vein laceration secondary to blunt thoraco-abdominal trauma. AB - Less than 25 cases of azygous vein lacerations secondary to blunt trauma have been published in the medical literature, most of these injuries were resulting from motor vehicle accidents, but have been described due to falls or assaults. These lesions should be considered as thoracic great vessels injuries and if not recognized promptly carry a high morbidity and mortality. We report a case of a young male involved in a high-speed car collision, admitted to the emergency room in an unstable condition secondary to hypovolemic shock due to azygous vein injury. The patient underwent emergent right antero-lateral thoracotomy followed by sternotomy for surgical control of the vascular injury and resuscitation. Laparotomy and splenectomy were also required, the abdomen was closed. The thoracic cavity was left packed and closure was delayed for 48 h. The patient survived and was transferred to another hospital seven days later. PMID- 20576653 TI - The association of non-invasive cerebral and mixed venous oxygen saturation during cardiopulmonary resuscitation. AB - Mixed venous oxygen saturation (SvO(2)) is an accepted surrogate parameter for the ratio between oxygen delivery and demand and may thus be used to determine the adequacy of the function of the cardiopulmonary system. Cerebral oxygen saturation monitoring by near infrared spectroscopy is a non-invasive method for the determination of the cerebral oxygen delivery to demand ratio that is applicable outside the operating room or the intensive care unit and does not require calibration. The present case highlights the agreement of non-invasive cerebral and SvO(2) in an 87-year-old female cardiac surgery patient with severe aortic stenosis scheduled for transapical aortic valve replacement during prolonged cardiopulmonary resuscitation. PMID- 20576654 TI - Giant cell arteritis presenting as dysarthria and mediastinal mass. AB - Giant cell arteritis, Takayasu arteritis, and Horton disease are rare, idiopathic diseases that cause chronic inflammation and obliteration of large arteries, mainly the aorta and its major branches. Histological examination reveals multinucleated giants cells and clinical presentation is characterized by general symptoms and/or symptoms related to stenosis or occlusion of vessels. A case of a 50-year-old woman with neurological symptoms, cervicothoracic tumour with severe stenosis of the right subclavian artery and complete occlusion of common carotid artery is presented. PMID- 20576649 TI - Mechanisms of vascular aging: new perspectives. AB - This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics. PMID- 20576655 TI - For neonates undergoing cardiac surgery does thymectomy as opposed to thymic preservation have any adverse immunological consequences? AB - A best evidence topic in congenital cardiac surgery was written according to a structured protocol. The question addressed was whether neonatal thymectomy in patients undergoing cardiac surgery has any adverse immunological consequences. Altogether 164 papers were found using the reported search, of which nine papers represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. The thymus is the major production site of T cells, whose stocks are built-up during foetal and early postnatal life. However, its function diminishes after the first years of life, and although thymic output is maintained into adulthood, the thymus mostly degenerates into fatty tissue in elderly adults. To date, there has been no general consensus with regard to the importance of this organ during childhood and adulthood. As a consequence, during cardiac surgery in neonates, partial or total thymectomy is routinely performed to enable better access to the heart and great vessels to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Interestingly, current best available evidence from nine case-control studies suggests that neonatal thymectomy affects peripheral T-cell populations both in the short- as well as long-term and results in premature immunosenescence. However, the impact of these changes on the risk of infectious diseases or malignancy has not been thoroughly evaluated by any of these studies. Maintenance of a registry of patients undergoing neonatal thymectomy and further studies to assess the functional or clinical consequences of this practice would be valuable. PMID- 20576656 TI - Thoracoscopic approach in the treatment of breast cancer relapse in the internal mammary lymph node. AB - Regional recurrence of breast cancer may involve the surgical site of mastectomy, axillary lymph nodes and the internal mammary lymphatic chain. Treatment of regional recurrent mammary cancer rarely requires thoracic surgery intervention, except in some selected cases of recurrence in the chest wall. Concerning lymphatic recurrence in breast cancer, the therapeutic choice rarely includes surgical lymph node excision. Exclusive videothoracoscopic (VTS) resection of recurrence in internal mammary lymph nodes has not as yet been reported in the literature. Due to the rare surgical exploration of this lymphatic chain, the thoracoscopic approach is described only in three published studies involving humans, furthermore, in these three descriptions, the operation was performed only for mere staging but not for the whole resection of the recurrent lymphatic structure. We present a case of recurrence of breast cancer in lymph nodes of the internal mammary chain that was treated with complete resection by pure VTS surgery. PMID- 20576658 TI - Peanut oil and peanut allergy, foes or folks? PMID- 20576657 TI - One-third of the new paediatric patients with sickle cell disease in The Netherlands are immigrants and do not benefit from neonatal screening. AB - OBJECTIVES: To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with diagnoses through neonatal screening To estimate the proportion of children with SCD receiving paediatric care in a comprehensive care setting. DESIGN: Data from two sources, a survey of paediatric practices (n=107) and a laboratory database (n=20), were analysed by the capture recapture method. PARTICIPANTS: Children with SCD aged <18 years, either born before 2003 or newly diagnosed as having SCD between 2003 and 2007. MAIN OUTCOME MEASURES: Prevalence, annual number of children newly diagnosed as having SCD, proportion of children with diagnoses through neonatal screening, proportion of children receiving paediatric care. RESULTS: The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1:5152 (95% CI 1:4513 to 1:6015). In the next 4 years, the annual incidence was 1:2011 (95% CI 1:1743 to 1:2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians. CONCLUSION: The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefit from neonatal screening and are at high risk of life threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered. PMID- 20576659 TI - Thyroid function at diagnosis of type I diabetes. AB - BACKGROUND: National guidelines recommend that thyroid function is assessed at diagnosis of type I diabetes (TIDM) and annually thereafter. This paper reports an audit of thyroid surveillance in accordance with this guideline. PATIENTS: 110 patients (66 males), median age 11.3 (1.2-15.7) years at diagnosis of TIDM, were monitored for 2.3 (0.7-4.2) years. RESULTS: 21/110 (19.0%) patients had abnormal thyroid function at diagnosis of TIDM. Of these, 16 had normal thyroid function on reassessment after 45 (3-540) days. Abnormalities of thyroid function occurred more commonly in children with diabetic ketoacidosis (DKA) than those who did not have DKA (9/29, 31.0% vs 12/81, 14.8%, p<0.025). At the end of the observation period, five (4.5%) patients had minor abnormalities of thyroid function not requiring treatment and three (2.7%) were treated. CONCLUSIONS: Transient abnormalities of thyroid function are common at diagnosis of TIDM, and therefore, thyroid hormones should not be measured at this time. PMID- 20576660 TI - Skeletal morbidity in children receiving chemotherapy for acute lymphoblastic leukaemia. AB - BACKGROUND: Children receiving chemotherapy for acute lymphoblastic leukaemia (ALL) may be susceptible to skeletal morbidity. AIM: To determine the incidence and risk factors for skeletal morbidity in ALL children. PATIENTS AND METHODS: The medical records of all (n=186, boys=110) children presenting to a single centre with ALL between 1997 and 2007 and treated on UKALL97, UKALL97/01 or UKALL2003 were studied. Skeletal morbidity included musculoskeletal pain, fractures and osteonecrosis (ON). Musculoskeletal pain was classified as any event of limb pain, muscle pain, joint symptoms or back pain that required radiological examination. Fractures and ON were confirmed by x-rays and MRI, respectively. RESULTS: Skeletal morbidity, presenting as musculoskeletal pain, fractures or ON were reported in 88 (47%) children of whom 56 (63%) were boys. Of 88 children, 49 (55%), 27 (30%) and 18 (20%) had musculoskeletal pain, fracture(s) or ON, respectively. 6 (7%) had fractures and ON. The median (10th, 90th centiles) age at diagnosis of ALL in those children without skeletal morbidity was 3.9 (1.4-12) years which was lower than in those with skeletal morbidity at 8.2 (2.2-14.3) years (p<0.00001, 95% CI 1.7 to 4.4). Children with ALL diagnosed over 8 years of age were at increased risk of developing fracture(s) (p=0.01, OR=2.9, 95% CI 1.3 to 6.5) whereas the risk of ON was higher in those who were diagnosed after 9 years of age (p<0.0001, OR=15, 95% CI 4.1 to 54.4). There was no sex difference in the incidence of skeletal complications. Children who received Dexamethasone had a higher incidence of skeletal morbidity than those who were treated with Prednisolone (p=0.027, OR=2.6, 95% CI 1.1 to 5.9). CONCLUSION: The occurrence of skeletal morbidity in ALL children may be influenced by age and the type of glucocorticoids. These findings may facilitate the development of effective bone protective intervention. PMID- 20576661 TI - Period problems: disorders of menstruation in adolescents. AB - Adolescence is a time of great psychological and physical change. In the UK, girls enter puberty around the age of 10 years with a median age of menarche of 12.9 years; thereafter, it may be several years before regular menstrual cycles are established. Variations in the type and the frequency of periods may create anxiety regarding ill health or serious underlying disorders. With the increase in childhood obesity and subsequent polycystic ovary syndrome, there is a greater awareness and presentation of girls with disorders of menstruation. This review focuses on normal variations of menses and common pathological causes of menstrual problems, including amenorrhoea, dysmenorrhoea and menorrhagia. Further consideration is given to the variations of presentation of polycystic ovary syndrome. It provides a guide to evaluate the various symptoms, investigations and management options. PMID- 20576662 TI - Doing the right thing. PMID- 20576663 TI - Outcomes of children born very preterm in Europe. PMID- 20576664 TI - Bilateral retinoblastoma presenting at retinopathy of prematurity screening. PMID- 20576665 TI - Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial. AB - OBJECTIVE: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. DESIGN: Single centre double blind randomized placebo controlled trial. SETTING: Cardiac rehabilitation centre. SUBJECTS AND INTERVENTION: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. MAIN MEASURES: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. RESULTS: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. CONCLUSION: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone. PMID- 20576666 TI - Patients' expectations and actual use of custom-made orthopaedic shoes. AB - OBJECTIVE: To investigate the association between patients' expectations and the actual use of custom-made orthopaedic shoes. DESIGN: A prospective cohort study with internal comparison. SETTING: Twelve orthopaedic shoe companies. PATIENTS: During six months, consecutive patients who were provided with their first ever pair of orthopaedic shoes and aged 16 years or older were recruited. A total of 339 patients with different pathologies were included (response 67%). Mean (SD) age of the patients was 63 (15) years, and 129 patients (38%) were male. MAIN MEASURES: A practical and reproducible questionnaire, measuring: frequency of use of orthopaedic shoes, patients' expectations and experiences of aspects of the usability of orthopaedic shoes, and communication about patients' expectations. RESULTS: Patients' expectations were not associated with the use of orthopaedic shoes (P-values range: 0.106 to 0.607), but the difference between expectations and experiences was (P-values range: <0.001 to 0.012). The expectations of patients who frequently used their orthopaedic shoes were in concordance with their experiences, whereas the expectations of patients who did not use their orthopaedic shoes were much higher than their experiences. There was no communication of patients' expectations with the medical specialist or orthopaedic shoe technician in 34% and 25% of the patients respectively. CONCLUSIONS: In relation to the actual use of orthopaedic shoes, it is crucial that patients' expectations are not much higher than their experiences. PMID- 20576667 TI - Effectiveness of motor learning coaching in children with cerebral palsy: a randomized controlled trial. AB - OBJECTIVE: To evaluate effectiveness of motor learning coaching on retention and transfer of gross motor function in children with cerebral palsy. DESIGN: Block randomized trial, matched for age and gross motor function. SETTING: Coordinated, multinational study (Israel, Jordan and Palestinian Authority) in schools and rehabilitation centers. SUBJECTS: 78 children with spastic cerebral palsy, gross motor functional levels II and III, aged 66 to 146 months. INTERVENTIONS: 1 hr/day, 3 days/week for 3 months treatment with motor learning coaching or neurodevelopmental treatment: two groups. MAIN MEASURES: Gross motor function Measure (GMFM-66), stair-climbing mechanical efficiency (ME) and parent questionnaire rating their child's mobility. Immediate treatment effects were assessed after 3 months and retention determined from follow-up measurements 6 months after treatment. RESULTS: GMFM-66, ME and parent questionnaires were obtained from 65, 31 and 64 subjects, respectively. Although both groups increased GMFM-66 score over 3 months, measurements 6 months later indicated retention was significantly superior by 2.7 in the motor learning coaching children of level-II. Similar retention trend was evident for ME, increasing 6 months after motor learning coaching by 1.1% and declining 0.3% after neurodevelopmental treatment. Mobility performance in the outdoors and community environment increased 13% from 3 to 9 months after motor learning coaching and decreased 12% after neurodevelopmental treatment. Minor group differences occurred in children of level-III. CONCLUSIONS: In higher functioning children with cerebral palsy, the motor learning coaching treatment resulted in significantly greater retention of gross motor function and transfer of mobility performance to unstructured environments than neurodevelopmental treatment. PMID- 20576668 TI - Prioritizing patients for Community Rehabilitation Services: do clinicians agree on triage decisions? AB - OBJECTIVE: To evaluate agreement between independent clinician raters using a triage protocol to prioritize referrals for occupational therapy and physiotherapy within a community rehabilitation program. DESIGN: The priority category allocated to consecutive referrals by one of six clinicians in the referral office was compared with a second rating made by an independent occupational therapist, blinded to the initial priority rating. SETTING: A centralized referral office staffed by allied health and nursing professionals designed as a single point of access for sub acute and ambulatory services within a large metropolitan health network. PARTICIPANTS: 214 referrals for adults requiring community based occupational therapy or physiotherapy rehabilitation for orthopaedic, neurological or other conditions (such as falls or cardio respiratory conditions). MAIN MEASURE: Agreement (weighted kappa = kappa(w)) between the two ratings. RESULTS: Overall agreement was moderate (kappa(w) = 0.60), but disagreement occurred in 30% of cases. Professional discipline of the raters did not affect agreement. Agreement varied between diagnostic subgroups, with significantly lower agreement for referrals for rehabilitation following elective orthopaedic surgery (kappa(w) = 0.25) than the other categories combined. Differences in agreement were observed between the four triage categories, with the lowest observed agreement in the most urgent category. CONCLUSIONS: Clinicians in a centralized model of triage showed only moderate agreement when making decisions about client priority for community rehabilitation for occupational therapy and physiotherapy. PMID- 20576669 TI - Experienced emotional burden in caregivers: psychometric properties of the Involvement Evaluation Questionnaire in caregivers of brain injured patients. AB - OBJECTIVE: To examine the psychometric properties (internal consistency, discriminant validity, and responsiveness) of the Involvement Evaluation Questionnaire for Brain Injury measuring emotional burden in caregivers of patients with chronic acquired brain injury. DESIGN: Inception cohort study. SUBJECTS: Caregivers of chronic acquired brain injury patients. MAIN MEASURES: Besides the Involvement Evaluation Questionnaire for Brain Injury, the Family Assessment Device and the General Health Questionnaire were used. METHODS: Ninety eight caregivers filled out all questionnaires, of which 41 caregivers did this twice, before and after the persons they cared for had started a residential community reintegration programme. Cronbach's alpha and Intra class Correlation Coefficient were calculated for internal consistency. Pearson correlation coefficients were used for discriminant validity and Intra class Correlation Coefficient and Cohen's d were calculated to determine responsiveness. RESULTS: The internal consistency of the Involvement Evaluation Questionnaire for Brain Injury was good (alpha = 0.73-0.84; Intra class Correlation Coefficient = 0.69 0.76). As expected, low correlations were found between the Involvement Evaluation Questionnaire for Brain Injury and either the General Health Questionnaire (r = 0.11-0.40) or the Family Assessment Device subscales (r = 0.29-0.19). Regarding responsiveness of the Involvement Evaluation Questionnaire for Brain Injury, a moderate effect size was found (Cohen's d = 0.36) while the Intra class Correlation Coefficient was good (0.80). CONCLUSIONS: The Involvement Evaluation Questionnaire for Brain Injury measures the experienced emotional burden in caregivers of patients with chronic acquired brain injury and seems to be a promising new instrument with good internal consistency, discriminant validity and responsiveness. PMID- 20576670 TI - The impact of fatigue on cognitive functioning in patients with multiple sclerosis. AB - OBJECTIVE: To study the impact of physical and mental fatigue on cognitive complaints and cognitive performance in patients with multiple sclerosis. DESIGN: Cross-sectional study. SETTING: An outpatient neurology clinic. SUBJECTS: Eighty patients diagnosed with clinically definite multiple sclerosis. MEASURES: The subscales physical and mental fatigue of the Multidimensional Fatigue Inventory; the Hospital Anxiety and Depression Scale and the Cognitive Failure Questionnaire. Cognitive performance was assessed by an extensive neuropsychological test battery, including several tasks requiring effortful information processing. RESULTS: Both anxiety and depression and mental fatigue significantly contributed to cognitive complaints, explaining respectively about 9% and 39% of the total variance. The contribution of physical fatigue to cognitive complaints was not significant. Both physical and mental fatigue did not significantly contribute to cognitive performance in terms of mental speed, attention, memory and executive functioning. CONCLUSIONS: To refine interventions for those patients with cognitive complaints, we advise adding measurements of anxiety, depression and fatigue to their neuropsychological assessment. Fatigue permits extensive neuropsychological assessment, which is needed to detect cognitive impairment in multiple sclerosis. PMID- 20576671 TI - Gynecologic Oncology Group quality assurance audits: analysis and initiatives for improvement. AB - BACKGROUND: The Gynecologic Oncology Group (GOG) is a multi-institution, multi discipline Cooperative Group funded by the National Cancer Institute (NCI) to conduct clinical trials which investigate the treatment, prevention, control, quality of survivorship, and translational science of gynecologic malignancies. In 1982, the NCI initiated a program of on-site quality assurance audits of participating institutions. Each is required to be audited at least once every 3 years. In GOG, the audit mandate is the responsibility of the GOG Quality Assurance Audit Committee and it is centralized in the Statistical and Data Center (SDC). Each component (Regulatory, Investigational Drug Pharmacy, Patient Case Review) is classified as Acceptable, Acceptable, follow-up required, or Unacceptable. PURPOSE: To determine frequently occurring deviations and develop focused innovative solutions to address them. METHODS: A database was created to examine the deviations noted at the most recent audit conducted at 57 GOG parent institutions during 2004-2007. Cumulatively, this involved 687 patients and 306 protocols. RESULTS: The results documented commendable performance: Regulatory (39 Acceptable, 17 Acceptable, follow-up, 1 Unacceptable); Pharmacy (41 Acceptable, 3 Acceptable, follow-up, 1 Unacceptable, 12 N/A): Patient Case Review (31 Acceptable, 22 Acceptable, follow-up, 4 Unacceptable). The nature of major and lesser deviations was analyzed to create and enhance initiatives for improvement of the quality of clinical research. As a result, Group-wide proactive initiatives were undertaken, audit training sessions have emphasized recurring issues, and GOG Data Management Subcommittee agendas have provided targeted instruction and training. LIMITATIONS: The analysis was based upon parent institutions only; affiliate institutions and Community Clinical Oncology Program participants were not included, although it is assumed their areas of difficulty are similar. CONCLUSIONS: The coordination of the GOG Quality Assurance Audit program in the SDC has improved data quality by enhancing our ability to identify frequently occurring deviations and develop innovative solutions to avoid or minimize their occurrence in the future. PMID- 20576672 TI - Predicting missing quality of life data that were later recovered: an empirical comparison of approaches. AB - BACKGROUND AND PURPOSE: The aim was to compare simple imputation, multiple imputation, and modeling approaches to deal with 'missing' quality of life data. Data were obtained from five clinical trials, which employed a reminder system for follow-up questionnaires. Previous studies have compared imputation strategies by artificially removing data according to prespecified mechanisms. Our approach differs from previous study as actual collected data are utilized. METHODS: Data obtained by reminder were initially treated as missing. These missing values were imputed using a variety of simple and multiple imputation strategies. The trials were analyzed using the imputed datasets, and the resulting treatment effects compared to analyses using the full dataset including responses following reminders. A repeated measures model was also carried out on the available data and the pattern mixture models were employed. The accuracy of the different strategies was assessed by calculating the bias seen in the calculated treatment difference compared to the actual observed treatment difference. RESULTS: Baseline carried forward or last value carried forward were shown to be the best simple imputation methods in this setting. Multiple imputation using a regression model or predictive mean match model tended to provide treatment difference estimates with the least bias when compared to the actual observed data. Pattern mixture models did not perform well. Overall, the multiple imputation procedures were generally the least biased approaches. LIMITATIONS: A number of imputation and modeling procedures have been investigated but this list is not exhaustive. All the example datasets come from the same data source and perhaps studies from additional disease areas would have been useful. However, we feel the results are generalizable to other quality of life outcomes and clinical areas. CONCLUSIONS: Multiple imputation is recommended for missing quality of life data as it makes the assumption of missing at random which in the quality of life setting is more plausible than the assumption of missing completely at random for which most simple imputation methods are based. Pattern mixture models can be complex and did not perform well in this setting. PMID- 20576673 TI - Part 2: Home-based family caregiving at the end of life: a comprehensive review of published qualitative research (1998-2008). AB - Family caregivers are crucial for supporting home death. We reviewed published qualitative research on home-based family caregiving at end of life (1998-2008), synthesizing key findings and identifying gaps where additional research is needed. Multiple databases were searched and abstracts reviewed for a focus on family caregiving and palliative care; full articles were reviewed to extract data for this review. In total, 105 articles were included. Findings are presented in the following areas: the caregiving experience and contextual features; supporting family caregivers at end of life; caregiving roles and decision-making; and rewards, meaning and coping. We noted a lack of definitional clarity; a reliance on interview methods and descriptive, thematic analyses, and a relative lack of diversity of patient conditions. Research needs are identified in several areas, including the bereavement experience, caregiver ambivalence, access to services, caregiver meaning-making, and relational and contextual influences on family caregiving at end of life. PMID- 20576675 TI - Can evidence-based medicine become counter-productive? PMID- 20576674 TI - Cohort differences in personality in middle-aged women during a 36-year period. Results from the Population Study of Women in Gothenburg. AB - AIM: To investigate secular trends in personality traits in adult female populations. METHODS: Two representative, population-based cohorts of women, 38 (n = 318) and 50 (n = 593) years of age participated in a health examination in 1968 and 2004 in Gothenburg, Sweden. The Eysenck Personality Inventory (EPI) and Cesarec-Marke Personality Schedule (CMPS) were used to measure personality traits. Socioeconomic and lifestyle variables (personal income, education, marital status, children at home, physical activity and smoking) were reported. RESULTS: In both age groups, secular comparisons in psychological profile subscales showed an increase in dominance, exhibition, aggression and achievement. Only small divergences were seen concerning affiliation, guilt feelings, nurturance and succorance. EPI showed a corresponding rise in extroversion. Social data showed a statistically significant increase in percentage of unmarried women, personal income levels, and higher educational achievement. While around 70% of women in 1968-69 had elementary school education only, around 90% had high school or university education in 2004-05. CONCLUSIONS: The results indicate major transitions in the adult Swedish female population in the direction of a more stereotypically ''male'' personality profile, but not at the expense of traditionally socially important female traits, which remained constant. These results are consistent with the hypothesis that society and the environment influence personality. PMID- 20576678 TI - Many fathers visit the child health care centre, but few take part in parents' groups. AB - Fathers are expected to play an increasing part in the care of children, but fathers are not automatically included in studies of early childhood. In this paper we present Swedish fathers' experiences of child health care. In the study, a total of 237 out of 279 (85%) fathers of small children were telephone interviewed using a structured questionnaire. As many as 165 (70%) had visited the child health centre at some time - 91 (38%) regularly or quite often - and we found an association between visits to the child health centre and physician contacts on account of the child's illness. A common feature throughout was the fathers' positive view of the child health centre and its activities, with as many as 77 percent grading it as very good or good. Sixty-seven fathers (28%) had taken part in a parents' group, and here there was a positive association with being a first-time father and knowing about the child's birth weight and vaccinations. We conclude that professionals must find new ways to get fathers to come to child health care, and especially to parents' groups. PMID- 20576679 TI - Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration. AB - The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 +/- 0.1 in dDAVP+losartan (LSDL) vs. 1.1 +/- 0.1 ml.100 g(-1).day(-1) in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 +/- 0.5 in LSDL vs. 6.8 +/- 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 +/- 0.2 vs. 1.8 +/- 0.2 ml.100 g(-1).day(-1), P < 0.05) in association with decreased urine osmolality (2,600 +/ 83 vs. 3,256 +/- 110 mosmol/kgH(2)O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 +/- 6 vs. 176 +/- 10% in LSD, P < 0.01), p-AQP2 (177 +/- 13 vs. 214 +/- 12% in LSD, P < 0.05), and AQP3 (134 +/- 14 vs. 177 +/- 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the alpha(1)- and gamma-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory. PMID- 20576680 TI - Expression patterns of connective tissue growth factor and of TGF-beta isoforms during glomerular injury recapitulate glomerulogenesis. AB - Transforming growth factor (TGF)-beta(1), -beta(2), and -beta(3) are involved in control of wound repair and development of fibrosis. Connective tissue growth factor (CTGF) expression is stimulated by all TGF-beta isoforms and is abundant in glomerulosclerosis and other fibrotic disorders. CTGF is hypothesized to mediate profibrotic effects of TGF-beta(1) or to facilitate interaction of TGF beta(1) with its receptor, but its interactions with TGF-beta isoforms in nonpathological conditions are unexplored so far. Tissue repair and remodeling may recapitulate gene transcription at play in organogenesis. To further delineate the relationship between CTGF and TGF-beta, we compared expression patterns of CTGF and TGF-beta isoforms in rat and human glomerulogenesis and in various human glomerulopathies. CTGF mRNA was present in the immediate precursors of glomerular visceral and parietal epithelial cells in the comma- and S-shaped stages, but not in earlier stages of nephron development. During the capillary loop and maturing glomerular stages and simultaneous with the presence of TGF beta(1), -beta(2), and -beta(3) protein, CTGF mRNA expression was maximal and present only in differentiating glomerular epithelial cells. CTGF protein was also present on precursors of mesangium and glomerular endothelium, suggesting possible paracrine interaction. Concomitant with the presence of TGF-beta(2) and beta(3) protein, and in the absence of TGF-beta(1), CTGF mRNA and protein expression was restricted to podocytes in normal adult glomeruli. However, TGF beta(1) and CTGF were again coexpressed, often with TGF-beta(2) and -beta(3), in particular in podocytes in proliferative glomerulonephritis and also in mesangial cells in diabetic nephropathy and IgA nephropathy (IgA NP). Coordinated expression of TGF-beta isoforms and of CTGF may be involved in normal glomerulogenesis and possibly in maintenance of glomerular structure and function at adult age. Prolonged overexpression of TGF-beta(1) and CTGF is associated with development of severe glomerulonephritis and glomerulosclerosis. PMID- 20576681 TI - Vasopressin increases phosphorylation of Ser84 and Ser486 in Slc14a2 collecting duct urea transporters. AB - Vasopressin-regulated urea transport in the renal inner medullary collecting duct (IMCD) is mediated by two urea channel proteins, UT-A1 and UT-A3, derived from the same gene (Slc14a2) by alternative splicing. The NH(2)-terminal 459 amino acids are the same in both proteins. To study UT-A1/3 phosphorylation, we made phospho-specific antibodies to UT-A sequences targeting phospho-serines at positions 84 and 486, sites identified previously by protein mass spectrometry. Both antibodies proved specific, recognizing only the phosphorylated forms of UT A1 and -A3. Immunoblotting of rat IMCD suspensions or whole inner medullas showed that the V2R-selective vasopressin analog 1-deamino-8-d-arginine vasopressin (dDAVP) increases phosphorylation at Ser84 (in UT-A1 and UT-A3) and Ser486 (in UT A1) by about eightfold. Time course studies in rat IMCD suspensions showed maximum phosphorylation within 1 min of dDAVP exposure, consistent with the time course of vasopressin-stimulated phosphorylation of the vasopressin-sensitive water channel aquaporin-2 at Ser256. Confocal immunofluorescence in Brattleboro rat medullary tissue showed labeling limited to the IMCD, which increased markedly in response to dDAVP. Immuno-electron microscopy studies showed that both phosphorylated forms were present mainly in intracellular compartments in the presence of vasopressin. These studies demonstrate regulated phosphorylation of both UT-A1 and UT-A3 in response to vasopressin in a manner consistent with coordinate regulation of UT-A and aquaporin-2 in the renal IMCD. The findings add to prior evidence for vasopressin-induced phosphorylation of UT-A1, providing evidence that UT-A3 may be regulated by phosphorylation as well. PMID- 20576682 TI - Rab10 associates with primary cilia and the exocyst complex in renal epithelial cells. AB - Rab10, a mammalian homolog of the yeast Sec4p protein, has previously been associated with endocytic recycling and biosynthetic membrane transport in cultured epithelia and with Glut4 translocation in adipocytes. Here, we report that Rab10 associates with primary cilia in renal epithelia in culture and in vivo. In addition, we find that Rab10 also colocalizes with exocyst proteins at the base of nascent cilia, and physically interacts with the exocyst complex, as detected with anti-Sec8 antibodies. These data suggest that membrane transport to the primary cilum may be mediated by interactions between Rab10 and an exocyst complex located at the cilium base. PMID- 20576683 TI - Shear stress-induced volume decrease in C11-MDCK cells by BK-alpha/beta4. AB - Large-conductance, calcium-activated potassium channels (BK) are expressed in principal cells (PC) and intercalated cells (IC) in mammalian nephrons as BK alpha/beta1 and BK-alpha/beta4, respectively. IC, which protrude into the lumens of tubules, express substantially more BK than PC despite lacking sufficient Na-K ATPase to support K secretion. We previously showed in mice that IC exhibit size reduction when experiencing high distal flows induced by a high-K diet. We therefore tested the hypothesis that BK-alpha/beta4 are regulators of IC volume via a shear stress (tau)-induced, calcium-dependent mechanism, resulting in a reduction in intracellular K content. We determined by Western blot and immunocytochemical analysis that C11-Madin-Darby canine kidney cells contained a predominance of BK-alpha/beta4. To determine the role of BK-alpha/beta4 in tau induced volume reduction, we exposed C11 cells to tau and measured K efflux by flame photometry and cell volume by calcein staining, which changes inversely to cell volume. With 10 dynes/cm(2), calcein intensity significantly increased 39% and monovalent cationic content decreased significantly by 37% compared with static conditions. Furthermore, the shear-induced K loss from C11 was abolished by the reduction of extracellular calcium, addition of 5 mM TEA, or BK-beta4 small interfering (si) RNA, but not by addition of nontarget siRNA. These results show that BK-alpha/beta4 plays a role in shear-induced K loss from IC, suggesting that BK-alpha/beta4 regulate IC volume during high-flow conditions. Furthermore, these results support the use of C11 cells as in vitro models for studying BK related functions in IC of the kidney. PMID- 20576684 TI - The diguanylate cyclase YddV controls production of the exopolysaccharide poly-N acetylglucosamine (PNAG) through regulation of the PNAG biosynthetic pgaABCD operon. AB - In Gram-negative bacteria, production of adhesion factors and extracellular polysaccharides (EPS) is promoted by the activity of diguanylate cyclases (DGCs), a class of enzymes able to catalyse the synthesis of the signal molecule bis (3',5')-cyclic di-guanylic acid (c-di-GMP). In this report we show that in Escherichia coli, overexpression of the YddV protein, but not of other DGCs such as AdrA and YcdT, induces the production of the EPS poly-N-acetylglucosamine (PNAG) by stimulating expression of pgaABCD, the PNAG-biosynthetic operon. Stimulation of PNAG production and activation of pgaABCD expression by the YddV protein are abolished by inactivation of its GGDEF motif, responsible for DGC activity. Consistent with the effects of YddV overexpression, inactivation of the yddV gene negatively affects pgaABCD transcription and PNAG-mediated biofilm formation. pgaABCD regulation by the yddV gene also takes place in a mutant carrying a partial deletion of the csrA gene, which encodes the main regulator of pgaABCD expression, suggesting that YddV does not regulate pgaABCD through modulation of CsrA activity. Our results demonstrate that PNAG production does not simply respond to intracellular c-di-GMP concentration, but specifically requires the DGC activity of the YddV protein, thus supporting the notion that in E. coli, c-di-GMP biosynthesis by a given DGC protein triggers regulatory events that lead to activation of specific sets of EPS biosynthetic genes or proteins. PMID- 20576685 TI - Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion. AB - Bistable populations of bacteria give rise to two or more subtypes that exhibit different phenotypes. We have explored whether the periodontal pathogen Porphyromonas gingivalis exhibits bistable invasive phenotypes. Using a modified cell invasion assay, we show for the first time that there are two distinct subtypes within a population of P. gingivalis strains NCTC 11834 and W50 that display differences in their ability to invade oral epithelial cells. The highly invasive subtype invades cells at 10-30-fold higher levels than the poorly invasive subtype and remains highly invasive for approximately 12-16 generations. Analysis of the gingipain activity of these subtypes revealed that the highly invasive type had reduced cell-associated arginine-specific protease activity. The role of Arg-gingipain activity in invasion was verified by enhancement of invasion by rgpAB mutations and by inclusion of an Arg-gingipain inhibitor in invasion assays using wild-type bacteria. In addition, a population of DeltargpAB bacteria did not contain a hyperinvasive subtype. Screening of the protease activity of wild-type populations of both strains identified high and low protease subtypes which also showed a corresponding reduction or enhancement, respectively, of invasive capabilities. Microarray analysis of these bistable populations revealed a putative signature set of genes that includes oxidative stress resistance and iron transport genes, and which might be critical to invasion of or survival within epithelial cells. PMID- 20576686 TI - Essentiality and functional analysis of type I and type III pantothenate kinases of Mycobacterium tuberculosis. AB - Pantothenate kinase, an essential enzyme in bacteria and eukaryotes, is involved in catalysing the first step of conversion of pantothenate to coenzyme A (CoA). Three isoforms (type I, II and III) of this enzyme have been reported from various organisms, which can be differentiated from each other on the basis of their biochemical and structural characteristics. Though most bacteria carry only one of the isoforms of pantothenate kinases, some of them possess two isoforms. The physiological relevance of the presence of two types of isozymes in a single organism is not clear. Mycobacterium tuberculosis, an intracellular pathogen, possesses two isoforms of pantothenate kinases (CoaA and CoaX) belonging to type I and III. In order to determine which pantothenate kinase is essential in mycobacteria, we performed gene inactivation of coaA and coaX of M. tuberculosis individually. It was found that coaA could only be inactivated in the presence of an extra copy of the gene, while coaX could be inactivated in the wild-type cells, proving that CoaA is the essential pantothenate kinase in M. tuberculosis. Additionally, the coaA gene of M. tuberculosis was able to complement a temperature-sensitive coaA mutant of Escherichia coli at a non-permissive temperature while coaX could not. The coaX deletion mutant showed no growth defects in vitro, in macrophages or in mice. Taken together, our data suggest that CoaX, which is essential in Bacillus anthracis and thus had been suggested to be a drug target in this organism, might not be a valid target in M. tuberculosis. We have established that the type I isoform, CoaA, is the essential pantothenate kinase in M. tuberculosis and thus can be explored as a drug target. PMID- 20576687 TI - Identification of a bacterial di-haem cytochrome c peroxidase from Methylomicrobium album BG8. AB - The nucleotide sequence of an open reading frame (corB) downstream of the copper repressible CorA-encoding gene of the methanotrophic bacterium Methylomicrobium album BG8 was obtained by restriction enzyme digestion and inverse PCR. The amino acid sequence deduced from this gene showed significant sequence similarity to the surface-associated di-haem cytochrome c peroxidase (SACCP) previously isolated from Methylococcus capsulatus (Bath), including both c-type haem-binding motifs. Homology analysis placed this protein, phylogenetically, within the subfamily containing the M. capsulatus SACCP of the bacterial di-haem cytochrome c peroxidase (BCCP) family of proteins. Immunospecific recognition confirmed synthesis of the M. album CorB as a protein non-covalently associated with the outer membrane and exposed to the periplasm. corB expression is regulated by the availability of copper ions during growth and the protein is most abundant in M. album when grown at a low copper-to-biomass ratio, indicating an important physiological role of CorB under these growth conditions. corB was co-transcribed with the gene encoding CorA, constituting a copper-responding operon, which appears to be under the control of a sigma(54)-dependent promoter. M. album CorB is the second isolated member of the recently described subfamily of the BCCP family of proteins. So far, these proteins have only been described in methanotrophic bacteria. PMID- 20576689 TI - The type III secretion system of Vibrio alginolyticus induces rapid apoptosis, cell rounding and osmotic lysis of fish cells. AB - Vibrio alginolyticus is a Gram-negative bacterium and has been recognized as an opportunistic pathogen in humans as well as marine animals. However, the virulence mechanisms for this species of Vibrio have not been elucidated. This study characterized multiple mechanisms that induce cell death in fish cells upon infection with a V. alginolyticus strain, ZJO. The bacterium required its type III secretion system (T3SS) to cause rapid death of infected fish cells. Dying cells exhibited some features of apoptotic cells, such as membrane blebbing, nuclear condensation and DNA fragmentation. Further studies showed that caspase-3 was activated by the T3SS of the ZJO strain, confirming that infection with V. alginolyticus rapidly induces T3SS-dependent apoptosis in fish cells. Infection with the ZJO strain also led to membrane pore formation and release of cellular contents from infected fish cells, as evidenced by lactate dehydrogenase release and the uptake of a membrane-impermeable dye. Importantly, inhibition of apoptosis did not prevent ZJO-infected cells from releasing cellular contents and did not block cell rounding. Taken together, these data demonstrate that infection with V. alginolyticus may promote at least three different T3SS dependent events, which lead to the death of fish cells. This study provides an important insight into the mechanism used by Vibrio species to cause host-cell death. PMID- 20576688 TI - Agrobacterium tumefaciens ExoR represses succinoglycan biosynthesis and is required for biofilm formation and motility. AB - The ubiquitous plant pathogen Agrobacterium tumefaciens attaches efficiently to plant tissues and abiotic surfaces and can form complex biofilms. A genetic screen for mutants unable to form biofilms on PVC identified disruptions in a homologue of the exoR gene. ExoR is a predicted periplasmic protein, originally identified in Sinorhizobium meliloti, but widely conserved among alphaproteobacteria. Disruptions in the A. tumefaciens exoR gene result in severely compromised attachment to abiotic surfaces under static and flow conditions, and to plant tissues. These mutants are hypermucoid due to elevated production of the exopolysaccharide succinoglycan, via derepression of the exo genes that direct succinoglycan synthesis. In addition, exoR mutants have lost flagellar motility, do not synthesize detectable flagellin and are diminished in flagellar gene expression. The attachment deficiency is, however, complex and not solely attributable to succinoglycan overproduction or motility disruption. A. tumefaciens ExoR can function independently of the ChvG-ChvI two component system, implicated in ExoR-dependent regulation in S. meliloti. Mutations that suppress the exoR motility defect suggest a branched regulatory pathway controlling succinoglycan synthesis, motility and biofilm formation. PMID- 20576690 TI - The Candida albicans homologue of PIG-P, CaGpi19p: gene dosage and role in growth and filamentation. AB - Glycosylphosphatidyl inositol (GPI)-anchored proteins in Candida albicans are responsible for a vast range of functions, and deletions in certain GPI-anchored proteins severely reduce adhesion and virulence of this organism. In addition, completely modified GPIs are necessary for virulence. GPI anchor biosynthesis is essential for viability and starts with the transfer of N-acetylglucosamine to phosphatidylinositol. This step is catalysed by a multi-subunit complex, GPI-N acetylglucosaminyltransferase (GPI-GnT). In this, the first report to our knowledge on a subunit of the Candida GPI-GnT complex, we show that CaGpi19p is the functional equivalent of the Saccharomyces cerevisiae Gpi19p. An N-terminal truncation mutant of CaGpi19p functionally complements a conditionally lethal S. cerevisiae gpi19 mutant. Further, we constructed a conditional null mutant of CaGPI19 by disrupting one allele and placing the remaining copy under the control of the MET3 promoter. Repression leads to growth defects, cell wall biogenesis aberrations, azole sensitivity and hyperfilamention. In addition, there is a noticeable gene dosage effect, with the heterozygote also displaying intermediate degrees of most phenotypes. The mutants also displayed a reduced susceptibility to the antifungal agent amphotericin B. Collectively, the results suggest that CaGPI19 is required for normal morphology and cell wall architecture. PMID- 20576691 TI - Global transcriptomics analysis of the Desulfovibrio vulgaris change from syntrophic growth with Methanosarcina barkeri to sulfidogenic metabolism. AB - Desulfovibrio vulgaris is a metabolically flexible micro-organism. It can use sulfate as an electron acceptor to catabolize a variety of substrates, or in the absence of sulfate can utilize organic acids and alcohols by forming a syntrophic association with a hydrogen-scavenging partner to relieve inhibition by hydrogen. These alternative metabolic types increase the chance of survival for D. vulgaris in environments where one of the potential external electron acceptors becomes depleted. In this work, whole-genome D. vulgaris microarrays were used to determine relative transcript levels as D. vulgaris shifted its metabolism from syntrophic in a lactate-oxidizing dual-culture with Methanosarcina barkeri to a sulfidogenic metabolism. Syntrophic dual-cultures were grown in two independent chemostats and perturbation was introduced after six volume changes with the addition of sulfate. The results showed that 132 genes were differentially expressed in D. vulgaris 2 h after addition of sulfate. Functional analyses suggested that genes involved in cell envelope and energy metabolism were the most regulated when comparing syntrophic and sulfidogenic metabolism. Upregulation was observed for genes encoding ATPase and the membrane-integrated energy-conserving hydrogenase (Ech) when cells shifted to a sulfidogenic metabolism. A five-gene cluster encoding several lipoproteins and membrane-bound proteins was downregulated when cells were shifted to a sulfidogenic metabolism. Interestingly, this gene cluster has orthologues found only in another syntrophic bacterium, Syntrophobacter fumaroxidans, and four recently sequenced Desulfovibrio strains. This study also identified several novel c-type cytochrome encoding genes, which may be involved in the sulfidogenic metabolism. PMID- 20576692 TI - Cytoplasmic phytochrome action. AB - Phytochrome photoperception is a common mechanism for the detection of red and far-red light in bacteria, cyanobacteria, fungi and plants. However, the responses following phytochrome activation appear to be quite diverse between species. Lower plants, such as mosses, show phytochrome-mediated directional responses, namely phototropism and polarotropism. These cannot be explained by nuclear gene regulation and are thought to be triggered by phytochromes in the cytoplasm or at the plasma membrane. In higher plants, similar directional responses are mediated via phototropin, a blue light receptor, with phytochromes mainly controlling morphogenetic responses through gene regulation. However, cytoplasmic phytochrome responses exist in higher plants too, which appear to be intertwined with directional blue light perception. By summarizing the respective findings, a possible conservation of cytoplasmic phytochrome function in higher and lower plants is addressed here. PMID- 20576693 TI - Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection. AB - Congenital cytomegalovirus (CMV) infection is the leading nongenetic cause of congenital sensorineural hearing loss (SNHL). Hearing loss due to congenital CMV infection either has onset after the newborn period or shows progressive decline in auditory thresholds. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic and developmental sequelae. In symptomatically infected infants, ganciclovir therapy administered in the neonatal period prevents hearing deterioration. However, preventative therapy of asymptomatic congenital CMV disease is controversial. Here in, we reported a male newborn with asymptomatic congenital CMV with bilateral SNHL. Oral treatment with valganciclovir in patient resulted in progressive improvement of SNHL, which effectively reduced the CMV viral load and was well tolerated without apparent adverse effects. PMID- 20576694 TI - The effects of unequal access to health insurance for same-sex couples in California. AB - Inequities in marriage laws and domestic partnership benefits may have implications for who bears the burden of health care costs. We examined a recent period in California to illuminate disparities in health insurance coverage faced by same-sex couples. Partnered gay men are less than half as likely (42 percent) as married heterosexual men to get employer-sponsored dependent coverage, and partnered lesbians have an even slimmer chance (28 percent) of getting dependent coverage compared to married heterosexual women. As a result of these much lower rates of employer-provided coverage, partnered lesbians and gay men are more than twice as likely to be uninsured as married heterosexuals. The exclusion of gay men and women from civil marriage and the failure of domestic partnership benefits to provide insurance parity contribute to unequal access to health coverage, with the probable result that more health spending is pushed onto these individuals and onto the public. PMID- 20576695 TI - Loss and reorganization of calretinin-containing interneurons in the epileptic human hippocampus. AB - Calretinin is expressed mainly in interneurons that specialize to innervate either principal cell dendrites or other interneurons in the human hippocampus. Calretinin-containing cells were shown to be vulnerable in animal models of ischaemia and epilepsy. In the human hippocampus, controversial data were published regarding their sensitivity in epilepsy. Therefore we aimed to reveal the fate of this cell type in human epileptic hippocampi. Surgically removed hippocampi of patients with drug-resistant temporal lobe epileptic (n = 44) were examined and compared to control (n = 8) samples with different post-mortem delays. The samples were immunostained for calretinin and the changes in the distribution, density and synaptic target selectivity of calretinin-positive cells were analysed. Control samples with post-mortem delays longer than 8 h resulted in a reduced number of immunolabelled cells compared to controls with short post-mortem delay. The number of calretinin-positive cells in the epileptic tissue was considerably decreased in correlation with the severity of principal cell loss. Preserved cells had segmented and shortened dendrites. Electron microscopic examination revealed that in controls, 23% of the calretinin-positive interneuronal terminals targeted calretinin-positive dendrites, whereas in the epileptic samples it was reduced to 3-5%. The number of contacts between calretinin-positive dendrites also dropped. The present quantitative data suggest that calretinin-containing cells in the human hippocampus are highly vulnerable, thus inhibition mediated by dendritic inhibitory cells and their synchronization by interneuron-specific interneurons may be impaired in epilepsy. We hypothesize that reorganization of the interneuron-selective cells may be implicated in the occurrence of seizures in non-sclerotic patients, where the majority of principal and non-principal cells are preserved. PMID- 20576696 TI - Lockhart Clarke's contribution to the description of amyotrophic lateral sclerosis. AB - The definition of the clinicopathological entity of amyotrophic lateral sclerosis evolved over half a century. Although the definitive term amyotrophic lateral sclerosis that acknowledged both upper and lower motor neuron involvement was attributed to Jean-Martin Charcot in 1874, his initial case was published nearly a decade earlier; and it is accepted that, from at least the 1830s, several others (including Charles Bell, Francois-Amilcar Aran and Jean Cruveilhier) had already recognized a progressive lower motor neuron-only syndrome within a broader, clinically-defined group of disorders, termed progressive muscular atrophy. Although William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome, the term motor neuron disease, as an over-arching label, was not suggested until nearly a century later by W. Russell Brain. Augustus Jacob Lockhart Clarke (1817-80) is best known for his descriptions of spinal cord anatomy. However, in two detailed case reports from the 1860s, he carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of amyotrophic lateral sclerosis. Furthermore, he recognized the additional involvement of the corticospinal tracts that distinguished this from progressive muscular atrophy. Several aspects of the exquisite clinical histories documented as part of both studies, one by Charles Bland Radcliffe, resonate with contemporary debates concerning the evolution of disease in amyotrophic lateral sclerosis. These 'past masters' still have much to teach us. PMID- 20576698 TI - hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb alpha via IRES-mediated translation. AB - The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb alpha functions as a transcriptional repressor, affecting expression patterns of other clock genes. For the continuous and robust oscillation of the molecular clock system, the levels of Rev-erb alpha protein are expected to be tightly regulated with the correct timing. Here, we demonstrate that Rev-erb alpha has an internal ribosomal entry site (IRES) in its 5' untranslated region. Furthermore, we demonstrate that heterogeneous nuclear ribonucleoprotein Q and polypyrimidine tract-binding protein (PTB) modulate the IRES-mediated translation of Rev-erb alpha. We suggest that the rhythmic binding affinity of hnRNP Q to the Rev-erb alpha IRES and the change in PTB cytosolic levels lead to maintenance of the oscillation profile of the Rev-erb alpha protein. PMID- 20576701 TI - Editorial. Nucleic Acids Research annual Web Server Issue in 2010. PMID- 20576699 TI - Towards computational prediction of microRNA function and activity. AB - While it has been established that microRNAs (miRNAs) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual miRNAs are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human miRNAs. Our approach improves upon standard statistical tools by addressing specific characteristics of miRNA regulation. Our analysis is based on a novel compendium of experimentally verified miRNA-pathway and miRNA-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel miRNA-regulated pathways, refines the annotation of miRNAs for which only crude functions are known, and assigns differential functions to miRNAs with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify miRNAs and genomic miRNA clusters with functional importance in specific stages of early human development. A full list of the predicted mRNA functions is available at http://acgt.cs.tau.ac.il/fame/. PMID- 20576702 TI - BSQA: integrated text mining using entity relation semantics extracted from biological literature of insects. AB - Text mining is one promising way of extracting information automatically from the vast biological literature. To maximize its potential, the knowledge encoded in the text should be translated to some semantic representation such as entities and relations, which could be analyzed by machines. But large-scale practical systems for this purpose are rare. We present BeeSpace question/answering (BSQA) system that performs integrated text mining for insect biology, covering diverse aspects from molecular interactions of genes to insect behavior. BSQA recognizes a number of entities and relations in Medline documents about the model insect, Drosophila melanogaster. For any text query, BSQA exploits entity annotation of retrieved documents to identify important concepts in different categories. By utilizing the extracted relations, BSQA is also able to answer many biologically motivated questions, from simple ones such as, which anatomical part is a gene expressed in, to more complex ones involving multiple types of relations. BSQA is freely available at http://www.beespace.uiuc.edu/QuestionAnswer. PMID- 20576703 TI - The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. AB - GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. PMID- 20576697 TI - Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. AB - This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. In the former, impairment in a single cognitive domain was observed in 40%, with the same number showing impairment in multiple domains, while in the latter the figures were 28.6 and 13.5%, respectively. On the Frontal Assessment Battery, impairment was observed in 62.0% of patients with progressive supranuclear palsy and 31.8% of those with multiple system atrophy. Although the progressive supranuclear palsy group performed worse overall, the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical, with the main impairment of the Initiation and Perseveration subscale. The impaired patients in the two groups were largely indistinguishable, qualitatively and quantitatively. Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages (22% in multiple system atrophy and 50% in progressive supranuclear palsy). Where a pathological diagnosis was available, the original clinical diagnosis was confirmed in the majority of cases, including those with significant cognitive impairment. The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole. These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive profile similar to that previously reported in idiopathic Parkinson's disease. The results indicate a high level of cognitive impairment associated with progressive supranuclear palsy, but also point to comparable dysfunction in a substantial proportion of the patients with multiple system atrophy. Significant cognitive impairment appears consistent with a diagnosis of multiple system atrophy, even early in the disease, with important implications for diagnosis, research and management. PMID- 20576707 TI - Screening for breast cancer--balancing the debate. PMID- 20576708 TI - Rape as a weapon of war in modern conflicts. PMID- 20576709 TI - Budget crises, health, and social welfare programmes. PMID- 20576710 TI - Parenteral nutrition is given inappropriately in almost a third of adult cases, report says. PMID- 20576715 TI - The influence of the therapist-patient relationship on treatment outcome in physical rehabilitation: a systematic review. AB - BACKGROUND: The working alliance, or collaborative bond, between client and psychotherapist has been found to be related to outcome in psychotherapy. PURPOSE: The purpose of this study was to investigate whether the working alliance is related to outcome in physical rehabilitation settings. DATA SOURCES: A sensitive search of 6 databases identified a total of 1,600 titles. STUDY SELECTION: Prospective studies of patients undergoing physical rehabilitation were selected for this systematic review. DATA EXTRACTION: For each included study, descriptive data regarding participants, interventions, and measures of alliance and outcome-as well as correlation data for alliance and outcomes-were extracted. DATA SYNTHESIS: Thirteen studies including patients with brain injury, musculoskeletal conditions, cardiac conditions, or multiple pathologies were retrieved. Various outcomes were measured, including pain, disability, quality of life, depression, adherence, and satisfaction with treatment. The alliance was most commonly measured with the Working Alliance Inventory, which was rated by both patient and therapist during the third or fourth treatment session. The results indicate that the alliance is positively associated with: (1) treatment adherence in patients with brain injury and patients with multiple pathologies seeking physical therapy, (2) depressive symptoms in patients with cardiac conditions and those with brain injury, (3) treatment satisfaction in patients with musculoskeletal conditions, and (4) physical function in geriatric patients and those with chronic low back pain. LIMITATIONS: Among homogenous studies, there were insufficient reported data to allow pooling of results. CONCLUSIONS: From this review, the alliance between therapist and patient appears to have a positive effect on treatment outcome in physical rehabilitation settings; however, more research is needed to determine the strength of this association. PMID- 20576716 TI - Family priorities for activity and participation of children and youth with cerebral palsy. AB - BACKGROUND: Understanding family priorities for children and youth with cerebral palsy is essential for family-centered service. OBJECTIVE: The purposes of this study were: (1) to identify family priorities for activity and participation in children and youth with cerebral palsy and (2) to determine differences based on age and Gross Motor Functional Classification System (GMFCS) level. DESIGN: Five hundred eighty-five children and youth with cerebral palsy and their caregivers participated at regional children's hospitals. The children and youth were 2 to 21 years of age; 56% were male, and 44% were female. Their caregivers, predominantly mothers (80%), had a mean age of 40.3 years (SD=9.3). The Canadian Occupational Performance Measure was administered to caregivers to identify their priorities for their children. The priorities were coded into 3 categories (daily activities, productivity, and leisure) and 13 subcategories. The GMFCS levels were determined by assessors who met the criterion for reliability. Friedman and Kruskal-Wallis one-way analyses of variance were used to examine differences in priorities. RESULTS: Parents of children in all age groups and GMFCS levels II to V identified more priorities for daily activities. Parents of school-aged children and youth had more priorities for productivity than parents of younger children. For parents of children in all age groups and motor function levels, self-care was the most frequent priority subcategory. Sixty-one percent of parents identified at least one priority related to mobility. LIMITATIONS: The study did not include qualitative analysis of priorities of parents. CONCLUSIONS: Parents' priorities for their children and youth with cerebral palsy differed depending on age and gross motor function level; however, the most frequent priority for all age groups was daily activities. Interviews with families are recommended for identifying outcomes for activity and participation and developing an intervention plan. PMID- 20576717 TI - The contribution of cardiovascular risk factors to peripheral arterial disease in South Asians and Blacks: a sub-study to the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study. AB - OBJECTIVE: To determine whether differences exist in prevalence of peripheral arterial disease (PAD) between South Asians (people originating from India, Pakistan and Bangladesh) and Blacks (Black Caribbean and Black African), the two largest minority ethnic groups in the UK. To determine if associations with cardiovascular risk factors and this disease differ between these two ethnic groups. PATIENTS AND METHODS: We recruited 572 patients (356 South Asian and 216 Blacks) > or = 45 years as a sub-study to a community screening project, the Ethnic-Echocardiographic Heart of England Screening (E-ECHOES) study. All subjects completed an interviewer-led questionnaire, anthropometric measurements and blood sampling. Ankle brachial pressure index (ABPI) was calculated and intermittent claudication was assessed using the Edinburgh Claudication Questionnaire. The presence of PAD was defined as ABPI <0.9. RESULTS: The mean age was 62 years overall with no difference between the two ethnic groups. The prevalence of PAD was 13.2% [95% confidence interval (CI) 9.7-16.7] in South Asians and 10.2% (95% CI 6.2-14.2) in Blacks with no significant difference between the two ethnic groups. The prevalence of PAD was higher in South Asian women than Black women (16.3 vs. 6.1%; P = 0.011). No difference in prevalence was found in men (11 vs. 14% P = 0.47, in South Asians and Blacks, respectively). The prevalence of intermittent claudication was 0.9% (95% CI 0.11-1.63). On multivariate logistic regression, mean systolic blood pressure, diabetes, smoking and male sex were independently associated with PAD in South Asians (P = 0.016, 0.022, 0.037 and 0.008, respectively). In Blacks, only age remained independently associated with PAD on multivariate logistic regression (P = 0.003). CONCLUSION: The prevalence of PAD is similar in South Asians and Blacks, and similar to levels reported in pre-dominantly White populations. South Asian women had a higher prevalence of PAD than Black women, which is not explained by traditional cardiovascular risk factors. PMID- 20576718 TI - Inhaled granulocyte-macrophage colony stimulating factor for first pulmonary recurrence of osteosarcoma: effects on disease-free survival and immunomodulation. a report from the Children's Oncology Group. AB - PURPOSE: Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma. EXPERIMENTAL DESIGN: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated. RESULTS: Dose escalation to 1,750 microg twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively. CONCLUSIONS: Inhalation of GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen. PMID- 20576719 TI - BCIRG 001 molecular analysis: prognostic factors in node-positive breast cancer patients receiving adjuvant chemotherapy. AB - PURPOSE: There are currently no validated factors predictive of response to taxanes in patients with breast cancer. We analyzed specimens from patients included in the Breast Cancer International Research Group (BCIRG) 001 trial, a randomized study which showed the superiority of docetaxel/doxorubicin/cyclophosphamide over fluorouracil/doxorubicin/cyclophosphamide as adjuvant therapy for node-positive operable breast cancer in terms of disease-free survival (DFS) and overall survival (OS). EXPERIMENTAL DESIGN: Immunohistochemical assessment of biological markers included histologic grade, tumor size, estrogen and progesterone receptors, lymph node status, HER2, MUC1, Ki-67/MIB-1, p53, Bcl-2, Bax, Bcl-XL, BAG-1, beta-tubulin isotypes II, III and IV, tau protein, and detyrosinated alpha tubulin. Associations between selected parameters and survival were tested through univariate analyses, then completed with multivariate analyses and a bootstrap resampling technique. RESULTS: In univariate analysis histologic grade, tumor size, number of involved nodes, estrogen and progesterone receptor status, p53, Ki-67, tubulin III, and tau protein were associated both with DFS and with OS. In multivariate analysis estrogen and progesterone receptors, tumor size, number of involved nodes, and Ki-67 protein were associated both with DFS and with OS, whereas tau protein levels were correlated with DFS and tubulin III and P53 were correlated with OS. No interaction was observed between Ki-67 and treatment allocation. CONCLUSIONS: We conclude that the expression in primary tumors of Ki-67 and p53 protein, as well as of the microtubule-related parameters tau protein and tubulin III, are independent prognostic factors in patients receiving adjuvant chemotherapy for node-positive breast cancer but are not predictive of benefit from docetaxel-containing adjuvant chemotherapy. PMID- 20576720 TI - Morphology and optical properties of single- and multi-layer InAs quantum dots. AB - An understanding of the structural and optical properties of quantum dots (QDs) is critical for their use in optical communication devices. In this study, single and multi-layer self-organized InAs QDs grown on (001) GaAs substrates by molecular beam epitaxy (MBE) were investigated. High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images show that the lateral size of multi-layer InAs QDs are larger and flatter than single-layer InAs QDs, which are oval-shaped. The change in shape and size may be attributed to the presence of InGaAs spacer layers in multi-layer InAs QDs. Reciprocal spacer mapping and fast Fourier transformation images clearly show that InGaAs spacer layers present in the multi-layer InAs QDs structures help to release the strain originally existing in the QDs. In addition, the photoluminescence peak of the multi-layer InAs QDs is broader than QD in the single-layer one, which implies that the multi-layer InAs QDs size variation is more random than the single-layer one and this corresponds with the HAADF-STEM images. These results prove that spacer layers release strain influencing the morphology and optical properties of the QDs. PMID- 20576721 TI - Effects of icodextrin on the peritoneal membrane. An inaccurate comment. PMID- 20576725 TI - Post-transplant lymphoproliferative disorder in view of the new WHO classification: a more rational approach to a protean disease? AB - Post-transplant lymphoproliferative disorders (PTLDs) are serious, life threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation leading to a high mortality (30-60%). PTLD represents a heterogeneous group of lymphoproliferative diseases. They become clinically relevant because of the expansion of transplantation medicine together with the development of potent immunosuppressive drugs. Although the diagnostic morphological criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not always easy. Because of the limited number of clinical trials, a consensus is lacking on the optimal treatment of PTLD. This review focuses on incidence, risk factors, clinical picture of the disease and diagnostic tools including histopathology relating to the new classification introduced in 2008 by the World Health Organisation (WHO) and treatment of PTLD. PMID- 20576722 TI - Home dialysis is a successful strategy in nonrenal solid organ transplant recipients with end-stage renal disease. AB - BACKGROUND: Chronic kidney disease (CKD) is a common complication of solid organ transplantation with a substantial risk of progression to end-stage renal disease (ESRD). The impact of dialysis modality on morbidity and mortality is unknown in these patients. The aim of the present analysis was to describe our experience with home dialysis [peritoneal dialysis (PD) and home haemodialysis (HHD)] to assess the feasibility of this modality in patients who developed ESRD after nonrenal solid organ transplant (NRSOT). METHODS: A retrospective observational cohort study with consecutive patients initiated on home dialysis after NRSOT from 2000 to 2009 was conducted. We collected data on patient demographics, laboratory parameters and blood pressure as well as clinical adverse events using our electronic clinical database. RESULTS: Between 2000 and 2009, 25 patients [median age, 56 years; interquartile range (IQR), 43-65 years] initiated home dialysis. Ten patients started HHD and 15 patients initiated PD. The types of NRSOT were liver (n = 11), heart (n = 8), lung (n = 5) and heart-lung (n = 1). The median vintage of NRSOT at the time of dialysis initiation was 8.7 years (IQR, 6.3-11.4 years). The median home dialysis follow-up was 24 months (IQR, 15 53 months). The median values of blood pressure, phosphate, calcium, parathyroid hormone and haemoglobin were within the K/DOQI targets. The hospitalization and infection rates were 1 episode every 22 and 29 patient-months, respectively. Three patients switched to in-centre conventional HD during follow-up and eight patients died. CONCLUSIONS: . Home dialysis (PD and HHD) is a feasible and sustainable modality for patients with ESRD after NRSOT. Home dialysis offers several potential benefits, such as improved haemodynamic and metabolic control, which may be important in the NRSOT population. Home dialysis in patients who develop ESRD after NRSOT should be actively considered for this cohort. PMID- 20576726 TI - New insights into angiotensin, reactive oxygen and endothelial function. PMID- 20576727 TI - Specific requirements for bloodless cardiopulmonary bypass in neonates and infants; a review. AB - A miniaturized cardiopulmonary bypass circuit enables the safe performance, in selected pediatric patients, of bloodless open heart surgery. As the latest survival rates in neonatal and infant cardiac surgery have become satisfactory, investigators have concentrated upon the improvement of existing procedures. Institutional guidelines and multidisciplinary efforts undertaken in the pre- and postoperative periods are of great importance, concerning bloodless CPB and should be seriously pursued by all involved caregivers. This review reflects upon the selective, most relevant requirements for success of asanguinous neonatal and infant CPB: acceptable level of hemodilution during the CPB, patient preoperative hematocrit value and volume of CPB circuit. We present an assessment of practical measures that were also adapted in our institution to achieve an asanguinous CPB for neonatal and infant patients. PMID- 20576728 TI - In vitro and in vivo evaluation of Dideco's paediatric cardiopulmonary circuit for neonates weighing less than five kilograms. AB - The neonate cardiopulmonary bypass (CPB) circuit, including a KIDS D100 oxygenator (The Sorin Group, Mirandola, Italy) and a D130 arterial filter (The Sorin Group), was evaluated in vitro with respect to the removal of free micro gas bubbles. No gas bubbles > 40microm were measured after the arterial filter D130 upon manual introduction of 10 ml of air into the venous line or during the use of vacuum-assisted venous drainage (VAVD). The D130 arterial filter removed 88 % of gas bubbles < 40 microm during manual introduction of air into the venous line; however, only 50 % of gas bubbles < 40 microm were removed during the use of VAVD. The same CPB circuit was evaluated in vivo to compare with another CPB circuit, including a D901 oxygenator (The Sorin Group) and arterial filter D736 (The Sorin Group), in 155 neonates weighing < or =5 kg. The D100 circuit required significantly less priming volume than the D901 circuit. Postoperative haemoglobin was significantly higher, artificial ventilation time was significantly shorter and postoperative bleeding was significantly less in the D100 group. This neonate CPB circuit effectively removed the gas bubbles and required up to 37% less priming volume and, thus, decreased the need for blood transfusion. PMID- 20576729 TI - Determining the optimal pneumococcal vaccination strategy for adults: is there a role for the pneumococcal conjugate vaccine? AB - On February 24, 2010, the US Food and Drug Administration approved a 13-valent pneumococcal protein conjugate vaccine (PCV13) for use in children. Currently, the only pneumococcal vaccine approved for use in adults in the United States is the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although PPV23 provides partial protection against invasive pneumococcal disease, it does not appear to impact the risk of pneumonia in elderly patients or younger adults with comorbidities. Experience with PCV7 in children and studies of the immunogenicity of PCV7 in high-risk adults suggest that PCV13 may be effective in adults. However, prior receipt of PPV23 may blunt the antibody response to protein conjugate vaccination; thus, receipt of PPV23 could potentially diminish the benefit of subsequent pneumococcal conjugate vaccination. The approval of PCV13 for children has created a unique dilemma for physicians seeking to provide optimum protection for their high-risk adult patients. Potential options could include use of the PCV13 "off-label," perhaps followed by PPV23; withholding pneumococcal vaccination of adults while awaiting approval of PCV13; or continuing to use the PPV23. Although there are limited data on PCVs in adults, the availability of PCV13 for children will likely cause uncertainty for some physicians until there is updated official guidance regarding the optimum strategies for prevention of pneumococcal infection in adults. PMID- 20576730 TI - An alternative method of acute lung injury classification for use in observational studies. AB - BACKGROUND: In observational studies using acute lung injury (ALI) as an outcome, a spectrum of lung injury and difficult-to-interpret chest radiographs (CXRs) may hamper efforts to uncover risk factor associations. We assessed the impact of excluding patients with difficult-to-classify or equivocal ALI diagnosis on clinical and genetic risk factor associations for ALI after trauma. METHODS: This study was of a prospective cohort of 280 critically ill trauma patients. The primary outcome was the development of ALI. Patients were classified into one of three groups: (1) definite ALI (patients who fulfilled the American-European Consensus Conference [AECC] criteria for ALI), (2)equivocal ALI (patients who had difficult-to-interpret CXRs), and (3) definite non-ALI. We compared clinical and genetic ALI risk factor associations between two classification schemes: AECC classification (definite ALI vs rest) and alternative classification (definite ALI vs definite non-ALI, excluding equivocal ALI). RESULTS: Ninety-three (35%) patients were classified as definite ALI, 67 (25%) as equivocal, and 104 (39%) as definite non-ALI. Estimates of clinical and genetic ALI risk factor associations were farther from the null using the alternative classification. In a multivariable risk factor model, the C statistic of the alternative classification was significantly higher than that derived from the AECC classification (0.82 vs 0.74; P < .01). CONCLUSIONS: The ability to detect ALI risk factors may be improved by excluding patients with equivocal or difficult-to classify ALI. Such analyses may provide improved ability to detect clinical and genetic risk factor associations in future epidemiologic studies of ALI. PMID- 20576731 TI - Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD. AB - BACKGROUND: Rational prescription of antibiotics in acute exacerbations of COPD (AECOPD) requires predictive markers. We aimed to analyze whether markers of systemic inflammation can predict response to antibiotics in AECOPD. METHODS: We used data from 243 exacerbations out of 205 patients from a placebo-controlled trial on doxycycline in addition to systemic corticosteroids for AECOPD. Clinical and microbiologic response, serum C-reactive protein (CRP) level (cutoffs 5 and 50 mg/L), and serum procalcitonin level (PCT) (cutoffs 0.1 and 0.25 MUg) were assessed. RESULTS: Potential bacterial pathogens were identified in the majority of exacerbations (58%). We found a modest positive correlation between PCT and CRP (r = 0.46, P < .001). The majority of patients (75%) had low PCT levels, with mostly elevated CRP levels. Although CRP levels were higher in the presence of bacteria (median, 33.0 mg/L [interquartile range, 9.75-88.25] vs 17 mg/L [interquartile range, 5.0-61.0] [P = .004]), PCT levels were similar. PCT and CRP performed similarly as markers of clinical success, and we found a clinical success rate of 90% in patients with CRP <= 5 mg/L. A significant effect of doxycycline was observed in patients with a PCT level < .1 MUg/L (treatment effect, 18.4%; P = .003). A gradually increasing treatment effect of antibiotics (6%, 10%, and 18%), although not significant, was found for patients with CRP values of <= 5, 6-50, and > 50 mg/L, respectively. CONCLUSIONS: Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics. CRP might be a more valuable marker in these patients. PMID- 20576732 TI - Reported pneumonia in patients with COPD: findings from the INSPIRE study. AB - BACKGROUND: Pneumonia is an important complication of COPD and is reported more often in patients receiving inhaled corticosteroids (ICSs). Little is known about the clinical course and factors predisposing to pneumonia in patients with COPD. We investigated patient characteristics and symptoms occurring before pneumonia reports in the Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) study. METHODS: This was a 2-year, double-blind, double dummy parallel study of 1,323 patients randomized to salmeterol/fluticasone propionate 50/500 MUg bid (SFC) or tiotropium 18 MUg once daily (Tio). Baseline demographics, including serum C-reactive protein (CRP) levels, were measured, and daily record cards (DRCs) were completed. RESULTS: We identified 87 pneumonia reports from adverse event records (SFC=62; Tio=25) in 74 patients (SFC=50; Tio=24), compared with 2,255 exacerbations (SFC=1,185; Tio=1,070). Pneumonia was more common in patients with severe dyspnea and in those with a baseline CRP level>10 mg/L. Numbers of de novo pneumonias (events that were not preceded by symptoms of an exacerbation) were similar between treatment groups, but pneumonia was more likely after either a treated or untreated unresolved exacerbation in patients receiving ICSs (SFC=32; Tio=7). Similar results were seen when analysis was confined to radiologically confirmed events. CONCLUSIONS: Pneumonia is much less frequent than exacerbation in COPD. The excess of events with ICS treatment appears to be associated with protracted symptomatic exacerbations. Earlier identification and treatment of these events to prevent pneumonia merits further investigation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00361959; Study No.: SC040036; URL: clinicaltrials.gov. PMID- 20576733 TI - Efficiency of neural drive during exercise in patients with COPD and healthy subjects. AB - BACKGROUND: It is unknown whether efficiency of neural drive as expressed by a ratio of ventilation to the diaphragm electromyogram (EMGdi) in patients with COPD differs from that of healthy subjects during exercise and whether maximal neural drive is exhibited at the point of exercise termination. METHODS: We studied 12 male patients with COPD (mean +/- SD age, 62.8 +/- 10.3 years; FEV(1), 28.1 +/- 10.2% predicted) and 12 age- and sex-matched healthy subjects (age, 61.1 +/- 7.2 years, FEV(1), 101.5 +/- 11.9% predicted). EMGdi was recorded from a multipair esophageal electrode during a constant work (80% of maximal oxygen consumption derived from a previous incremental exercise test) treadmill exercise. Minute ventilation and oxygen consumption were also measured. RESULTS: Root mean square (RMS) of the EMGdi increased initially and reached a plateau at submaximal drive during constant load exercise in both patients with COPD and healthy subjects. The ratio of ventilation to EMGdi remained stable during exercise in healthy subjects from beginning to the end (100% +/- 70% at the beginning and 100% +/- 39% at the end, P > .05), whereas the ratio decreased gradually during exercise in patients with COPD (from 85% +/- 66% to 42% +/- 13%, P < .05). CONCLUSIONS: Efficiency of neural drive decreases in patients with COPD during treadmill exercise. Neural respiratory drive reached a submaximal plateau during constant load exercise in both healthy subjects and patients with COPD, indicating that it may not be the only factor determining exercise capacity. PMID- 20576734 TI - Effectiveness trial of an intensive communication structure for families of long stay ICU patients. AB - BACKGROUND: Formal family meetings have been recommended as a useful approach to assist in goal setting, facilitate decision making, and reduce use of ineffective resources in the ICU. We examined patient outcomes before and after implementation of an intensive communication system (ICS) to test the effect of regular, structured formal family meetings on patient outcomes among long-stay ICU patients. METHODS: One hundred thirty-five patients receiving usual care and communication were enrolled as the control group, followed by enrollment of intervention patients (n = 346), from five ICUs. The ICS included a family meeting within 5 days of ICU admission and weekly thereafter. Each meeting discussed medical update, values and preferences, and goals of care; treatment plan; and milestones for judging effectiveness of treatment. RESULTS: Using multivariate analysis, there were no significant differences between control and intervention patients in length of stay (LOS), the primary end point. Similarly, there were no significant differences in indicators of aggressiveness of care or treatment limitation decisions (ICU mortality, LOS, duration of ventilation, treatment limitation orders, or use of tracheostomy or percutaneous gastrostomy). Exploratory analysis suggested that in the medical ICUs, the intervention was associated with a lower prevalence of tracheostomy among patients who died or had do-not-attempt-resuscitation orders in place. CONCLUSIONS: The negative findings of the main analysis, in combination with preliminary evidence of differences among types of unit, suggest that further examination of the influence of patient, family, and unit characteristics on the effects of a system of regular family meetings may be warranted. Despite the lack of influence on patient outcomes, structured family meetings may be an effective approach to meeting information and support needs. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01057238 ; URL: www.clinicaltrials.gov. PMID- 20576735 TI - Antiendothelial Cell Antibodies in Patients With COPD. AB - BACKGROUND: Circulating antiendothelial cell antibodies (AECA) bind to endothelial antigens and induce endothelial cell damage. These antibodies have been detected in patients with collagen vascular diseases and systemic vasculitis. Recently, autoimmune mechanisms and vascular involvement have attracted attention in COPD. This study aimed to investigate the expression of AECA in patients with COPD. METHODS: A total of 116 patients with COPD, whose condition was established based on the Global Initiative for Chronic Obstructive Lung Disease criteria, were evaluated. Serum samples were examined for AECA by a cellular enzyme-linked immunosorbent assay using human umbilical vein endothelial cells. In addition, 157 subjects without any clinical or radiologic evidence of COPD or pulmonary disease served as a reference population. RESULTS: The patients with COPD exhibited significantly higher serum AECA concentrations than subjects in the reference population. The expression of AECA was significantly elevated in the patients with COPD, even when compared with that in smokers among the reference population who had similar smoking habits to the patients with COPD but normal spirometry. CONCLUSIONS: These findings suggest that an autoimmune component associated with endothelial cell damage is possibly involved in COPD. PMID- 20576736 TI - Survival following lobectomy and limited resection for the treatment of stage I non-small cell lung cancer<=1 cm in size: a review of SEER data. AB - BACKGROUND: Although lobectomy is the standard treatment for stage I non-small cell lung cancer (NSCLC), recent studies have suggested that limited resection may be a viable alternative for small-sized tumors. The objective of this study was to compare survival after lobectomy and limited resection among patients with stage IA tumors<=1 cm by using a large, US-based cancer registry. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 2,090 patients with stage I NSCLC<=1 cm in size who underwent lobectomy or limited resection (segmentectomy or wedge resection). We used propensity score analysis to adjust for potential differences in the baseline characteristics of patients in the two treatment groups. Overall and lung cancer-specific survival rates of patients undergoing lobectomy vs limited resection were compared in stratified and adjusted analyses, controlling for propensity scores. RESULTS: Overall, 688 (33%) patients underwent limited resection. For the entire cohort, we were not able to identify a difference in outcomes among patients treated with lobectomy vs limited resection, as demonstrated by an adjusted hazard ratio (HR) for overall survival (1.12; 95% CI, 0.93-1.35) and lung cancer-specific survival (HR, 1.24; 95% CI, 0.95-1.61). Similarly, when the cohort was divided into propensity score quintiles, we did not find a difference in survival rate between the two groups. CONCLUSIONS: Limited resection and lobectomy may lead to equivalent survival rates among patients with stage I NSCLC tumors<=1 cm in size. If confirmed in prospective studies, limited resection may be preferable for the treatment of small tumors because it may be associated with fewer complications and better postoperative lung function. PMID- 20576737 TI - Speciation genes in plants. AB - BACKGROUND: Analyses of speciation genes--genes that contribute to the cessation of gene flow between populations--can offer clues regarding the ecological settings, evolutionary forces and molecular mechanisms that drive the divergence of populations and species. This review discusses the identities and attributes of genes that contribute to reproductive isolation (RI) in plants, compares them with animal speciation genes and investigates what these genes can tell us about speciation. SCOPE: Forty-one candidate speciation genes were identified in the plant literature. Of these, seven contributed to pre-pollination RI, one to post pollination, prezygotic RI, eight to hybrid inviability, and 25 to hybrid sterility. Genes, gene families and genetic pathways that were frequently found to underlie the evolution of RI in different plant groups include the anthocyanin pathway and its regulators (pollinator isolation), S RNase-SI genes (unilateral incompatibility), disease resistance genes (hybrid necrosis), chimeric mitochondrial genes (cytoplasmic male sterility), and pentatricopeptide repeat family genes (cytoplasmic male sterility). CONCLUSIONS: The most surprising conclusion from this review is that identities of genes underlying both prezygotic and postzygotic RI are often predictable in a broad sense from the phenotype of the reproductive barrier. Regulatory changes (both cis and trans) dominate the evolution of pre-pollination RI in plants, whereas a mix of regulatory mutations and changes in protein-coding genes underlie intrinsic postzygotic barriers. Also, loss-of-function mutations and copy number variation frequently contribute to RI. Although direct evidence of positive selection on speciation genes is surprisingly scarce in plants, analyses of gene family evolution, along with theoretical considerations, imply an important role for diversifying selection and genetic conflict in the evolution of RI. Unlike in animals, however, most candidate speciation genes in plants exhibit intraspecific polymorphism, consistent with an important role for stochastic forces and/or balancing selection in development of RI in plants. PMID- 20576738 TI - Ancient genome duplications during the evolution of kiwifruit (Actinidia) and related Ericales. AB - BACKGROUND AND AIMS: To assess the number and phylogenetic distribution of large scale genome duplications in the ancestry of Actinidia, publicly available expressed sequenced tags (ESTs) for members of the Actinidiaceae and related Ericales, including tea (Camellia sinensis), were analysed. METHODS: Synonymous divergences (K(s)) were calculated for all duplications within gene families and examined for evidence of large-scale duplication events. Phylogenetic comparisons for a selection of orthologues among several related species in Ericales and two outgroups permitted placement of duplication events in relation to lineage divergences. Gene ontology (GO) categories were analysed for each whole-genome duplication (WGD) and the whole transcriptome. KEY RESULTS: Evidence for three ancient WGDs in Actinidia was found. Analyses of paleologue GO categories indicated a different pattern of retained genes for each genome duplication, but a pattern consistent with the dosage-balance hypothesis among all retained paleologues. CONCLUSIONS: This study provides evidence for one independent WGD in the ancestry of Actinidia (Ad-alpha), a WGD shared by Actinidia and Camellia (Ad beta), and the well-established At-gamma WGD that occurred prior to the divergence of all taxa examined. More ESTs in other taxa are needed to elucidate which groups in Ericales share the Ad-beta or Ad-alpha duplications and their impact on diversification. PMID- 20576739 TI - Patterns of style polymorphism in five species of the South African genus Nivenia (Iridaceae). AB - BACKGROUND AND AIMS: Heterostylous plants have been characterized by the presence of two or three discrete morphs that differ in their sex organ position within populations. This polymorphism is widely distributed among the angiosperms, but detailed studies are limited to few taxonomic groups. Although a small representation, evolutionary meaningful variations of the heterostylous syndrome have been reported when precise measurements of the sexual whorls were taken. A thorough exploration of groups where heterostyly has been reported should offer new opportunities to further testing the evolutionary hypotheses explaining heterostyly. Here, the traits defining heterostyly were explored in half of the species in Nivenia, the only genus of Iridiaceae where heterostyly has been reported. METHODS: Detailed morphometric analysis of the flower sexual whorls and some traits considered as ancillary are supplied to determine for each population (a) the kind of stylar polymorphism, (b) the morph ratio and (c) the degree of reciprocity between sexual whorls. Also the rates of assortative (within morph) versus disassortative (between morphs) pollen transfer were estimated by analysing pollen loads on stigmas. The association between floral phenotypic integration and the reciprocity between sexual whorls was estimated; both characteristics have been quoted as dependent on the accuracy of the fit between pollinators and flowers and therefore related to the efficiency of pollen transfer. KEY RESULTS: Different types of polymorphism, differing in their degree of reciprocity, were found in Nivenia. Effective disassortative mating appears to be common, since (a) all dimorphic populations show equal morph-ratios (isoplethy), and (b) the pollen placed on the stigmas of each morph is likely to be coming from the other (complementary) morph. The most reciprocal populations of the heterostylous species have also the highest values of phenotypical integration. CONCLUSIONS: Stigma height dimorphism, as opposed to distyly, is proven for the first time in Nivenia. The presence of different types of polymorphism within the genus is consistent with hypotheses of the evolution of heterostyly. The role of the pollinators as the leading force of the transition seems to be apparent, since floral integration is related to reciprocity. PMID- 20576740 TI - Differential involvement of insulin-like growth factor-I and estrogen on prolactin cells in the mouse anterior pituitary. AB - Estrogen and insulin-like growth factor-I (IGF-I) stimulate prolactin (PRL) production, release and proliferation of PRL-producing cells (PRL cells) in the anterior pituitary. PRL cells in adult estrogen receptor alpha (ERalpha) knockout (alphaERKO) mice and IGF-I knockout (IGF-IKO) mice are decreased considerably in number. To investigate a correlation between 17beta-estradiol (E2) and IGF-I on PRL production, IGF-I wild-type (WT) or IGF-IKO mice were ovariectomized at day 8 and the number of PRL cells was examined at days 20 and 60. Although PRL cell number at day 20 and WT or IGF-IKO mice ovariectomized at day 8 was similar to that in intact WT or IGF-IKO mice, PRL cells in adult WT or IGF-IKO mice ovariectomized at day 8 were significantly decreased as compared with those in intact WT or IGF-IKO mice. Therefore, estrogen is essential for PRL cell differentiation between days 20 and 60, regardless of IGF-I. While PRL cells in WT ovariectomized mice increased from days 20 to 60, those in IGF-IKO ovariectomized mice did not increase, suggesting that IGF-I modified PRL cell differentiation after day 20. ICI 182,780 (anti-estrogen) treatment canceled an increase of PRL cells in 30-day-old ovariectomized WT mice, indicating that the presence of ERalpha is important. The number of PRL cells in alphaERKO mice was similar to that in WT mice at day 20; however, PRL cells in alphaERKO mice at day 60 were not increased in number from day 20, supporting the idea that estrogen is essential for PRL cell differentiation after day 20. Finally, the percentage of PRL cells in IGF-IKO mice was decreased as compared with that in WT mice at day 20; therefore, IGF-I affects PRL cells before day 20. In conclusion, PRL cell differentiation is differently regulated by E2 and IGF-I depending on the age. PMID- 20576741 TI - Vagal modulation of heart rate variability during atrial fibrillation in pigs. AB - Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia and is associated with an increased risk for sudden cardiac death. The ventricular rhythm is irregular and displays both non-linear and linear patterns; however, it has not been determined whether vagally derived patterns are manifest within the irregular rhythm. Moreover, indices of increased vagal control are associated with reduced risk of sudden cardiac death. In this study, we sought to determine whether the ventricular rhythm pattern during AF is, in part, modulated by vagal activity. Vagal oscillations were forced at 0.15 Hz by neck suction in 12 pigs with sustained AF with and without glycopyrrolate (0.15 microg/kg, intravenously) vagal blockade. Vagal activity was evaluated using time- and frequency-domain heart rate variability measures. The standard deviation of RR intervals (SDRRI) was significantly increased during vagal activation compared with baseline (P = 0.006). Moreover, SDRRI correlated significantly with spectral power at 0.15 Hz during baseline (r = 0.90, P < .001) and vagal activation (r = 0.86, P < 0.05). Glycopyrrolate blocked the increase in SDRRI (P < 0.001) and blunted spectral power at 0.15 Hz (P < 0.05). These results indicate that: (1) power spectral analysis may be used to assess parasympathetic regulation during AF, and (2) vagal oscillations produce an entrainment of the ventricular rhythm during AF in pigs. PMID- 20576742 TI - The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation. AB - In an ovine model of placental insufficiency-induced intrauterine growth retardation (PI-IUGR), characterized by hypoxia, hypoglycemia and a significant reduction in fetal weight, we assessed alterations in fetal and placental polyols. Arterial maternal-fetal concentration differences of glucose and mannose were greater in the PI-IUGR fetus; glucose: C (n = 7), 2.68 +/- 0.14 mmol/L versus PI-IUGR (n = 9), 3.18 +/- 0.16 mmol/L (P < 0.02) and mannose: C, 42.9 +/- 8.1 micromol/L versus PI-IUGR, 68.5 +/- 19.1 micromol/L (P < 0.001). For PI-IUGR fetuses, fetal arterial plasma myo-inositol concentrations were significantly increased (P < 0.001). The concentrations of sorbitol, glucose and fructose were significantly reduced (P < 0.03, 0.01, 0.02, respectively). The cotyledons of IUGR placentas had a significantly increased concentration of myo-inositol (P < 0.003) and decreased concentrations of sorbitol, fructose and glycerol (P < 0.01, 0.02, 0.01, respectively). Fetal hepatic concentrations of sorbitol (P < 0.001) and fructose (P < 0.03) were also significantly reduced. These profound changes in both placental and fetal concentrations of polyols and sugars in sheep PI-IUGR pregnancies support the conclusion that within the PI-IUGR placenta there is an increased flux through the glucose 6-P:inositol 1-P cyclase system and decreased flux through the polyol dehydrogenase system, leading to increased placental myo inositol production and decreased sorbitol production. The decreased placental supply of sorbitol to the fetal liver may lead to decreased fetal hepatic fructose production. These observations highlight that, in association with hypoxic and hypoglycemic PI-IUGR fetuses, there are major placental and fetal alterations in polyol production. The manner in which these alterations in fetoplacental carbohydrate metabolism contribute to the pathophysiology of PI IUGR is currently unknown. PMID- 20576743 TI - Salivary cortisol in a middle-aged community sample: results from 990 men and women of the KORA-F3 Augsburg study. AB - OBJECTIVE: Analysis of salivary cortisol concentrations and derived indices is increasingly used in clinical and scientific medicine. However, comprehensive data on these parameters in the general population are scarce. The aim of this study was to evaluate the concentrations of salivary cortisol in a large middle aged community sample and to identify major factors associated with altered hormone levels. DESIGN: We conducted a cross-sectional study within the Cooperative Health Research in the Region of Augsburg (KORA)-F3 study. A total of 1484 participants aged 50-69 years (52% women) had agreed to provide four saliva samples during a regular weekday. METHODS: We measured salivary cortisol concentrations at wake-up (F0), (1/2) h (F(1/2)), 8 h (F8), and 14 h (F14) after waking. We calculated cortisol awakening response (CAR), slope, and area under the curve (AUC(G)) of the circadian cortisol secretion. Sociodemographic and clinical characteristics were evaluated by interview and questionnaires, sampling conditions by protocol. In total, 1208 participants returned saliva samples, exclusion criteria left 990 subjects for final analyses. RESULTS: Salivary cortisol levels were (means+/-s.d.) F0=13.7+/-7.6, F(1/2)=20.5+/-9.8, F8=5.4+/ 3.3, and F14=2.0+/-1.8 nmol/l. Earlier sampling times were associated with higher CAR and smaller slope. Cortisol secretion was also influenced by gender and smoking habits. Higher perceived social support was associated with lower AUC(G) and smaller slope. CONCLUSIONS: We provide data on salivary cortisol concentrations in a large middle-aged community sample. Gender, sampling time, smoking habits, and perceived social support appeared as determinants of cortisol secretion. PMID- 20576744 TI - The use of text messaging to improve asthma control: a pilot study using the mobile phone short messaging service (SMS). AB - We have evaluated the feasibility of using the mobile phone short message service (SMS) for symptom monitoring in patients with asthma. All consecutive patients admitted to hospital for asthma during an 11-month period were considered for enrollment (n = 497). Those meeting the inclusion criteria were randomized into a control (n = 60) and intervention group (n = 60). Patients in the intervention group received SMS messages according to a structured workflow, while patients in the control group had no SMS support. In the intervention group, the mean response rate to the messages was 82%. There was an improvement in the Asthma Control Test (ACT) scores in 36 subjects in the intervention group compared to 28 subjects in the control group. There were reductions in the number of nebulizations in 54 subjects in the control group compared to 50 subjects in the intervention group, and reductions in emergency department visits in 57 subjects in the control group compared to 51 subjects in the intervention group. However, none of these differences were significant. There was no reduction in admission rates in either group (P = 0.5). The service was accepted by most patients, but its long-term effectiveness on the management of asthma remains to be determined. PMID- 20576745 TI - Feasibility of dynamic cardiac ultrasound transmission via mobile phone for basic emergency teleconsultation. AB - We assessed the feasibility of using a camcorder mobile phone for teleconsulting about cardiac echocardiography. The diagnostic performance of evaluating left ventricle (LV) systolic function was measured by three emergency medicine physicians. A total of 138 short echocardiography video sequences (from 70 subjects) was selected from previous emergency room ultrasound examinations. The measurement of LV ejection fraction based on the transmitted video displayed on a mobile phone was compared with the original video displayed on the LCD monitor of the ultrasound machine. The image quality was evaluated using the double stimulation impairment scale (DSIS). All observers showed high sensitivity. There was an improvement in specificity with the observer's increasing experience of cardiac ultrasound. Although the image quality of video on the mobile phone was lower than that of the original, a receiver operating characteristic (ROC) analysis indicated that there was no significant difference in diagnostic performance. Immediate basic teleconsulting of echocardiography movies is possible using current commercially-available mobile phone systems. PMID- 20576746 TI - Foot ulcer caused by multidrug-resistant Mycobacterium tuberculosis in a diabetic patient. AB - Osteoarticular tuberculosis is the fourth leading type of extrapulmonary tuberculosis. The disease has a progressive course and the diagnosis is often made in the later stages of bone destruction. We describe a case of a foot ulcer caused by drug-resistant Mycobacterium tuberculosis in a patient with known diabetes where the diagnosis was not suspected initially. Although tuberculous foot ulcers are rare, they should be included in the differential diagnosis of unknown foot ulcers. A greater awareness of this rare clinical entity may help in commencing specific evidence-based therapy quickly and preventing undue morbidity and mortality. PMID- 20576747 TI - Bacterial lipopolysaccharides variably modulate in vitro biofilm formation of Candida species. AB - The objective of this study was to evaluate the effect of the bacterial endotoxin LPS on Candida biofilm formation in vitro. The effect of the LPS of Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens and Salmonella typhimurium on six different species of Candida, comprising Candida albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, Candida tropicalis ATCC 13803, Candida parapsilosis ATCC 22019 and Candida dubliniensis MYA 646, was studied using a standard biofilm assay. The metabolic activity of in vitro Candida biofilms treated with LPS at 90 min, 24 h and 48 h was quantified by XTT reduction assay. Viable biofilm-forming cells were qualitatively analysed using confocal laser scanning microscopy (CLSM), while scanning electron microscopy (SEM) was employed to visualize the biofilm structure. Initially, adhesion of C. albicans was significantly stimulated by Pseudomonas and Klebsiella LPS. A significant inhibition of Candida adhesion was noted for the following combinations: C. glabrata with Pseudomonas LPS, C. tropicalis with Serratia LPS, and C. glabrata, C. parapsilosis or C. dubliniensis with Salmonella LPS (P<0.05). After 24 h of incubation, a significant stimulation of initial colonization was noted for the following combinations: C. albicans/C. glabrata with Klebsiella LPS, C. glabrata/C. tropicalis/C. krusei with Salmonella LPS. In contrast, a significant inhibition of biofilm formation was observed in C. glabrata/C. dubliniensis/C. krusei with Pseudomonas LPS, C. krusei with Serratia LPS, C. dubliniensis with Klebsiella LPS and C. parapsilosis/C. dubliniensis /C. krusei with Salmonella LPS (P<0.05). On further incubation for 48 h, a significant enhancement of biofilm maturation was noted for the following combinations: C. glabrata/C. tropicalis with Serratia LPS, C. dubliniensis with Klebsiella LPS and C. glabrata with Salmonella LPS, and a significant retardation was noted for C. parapsilosis/C. dubliniensis/C. krusei with Pseudomonas LPS, C. tropicalis with Serratia LPS, C. glabrata/C. parapsilosis/C. dubliniensis with Klebsiella LPS and C. dubliniensis with Salmonella LPS (P<0.05). These findings were confirmed by SEM and CLSM analyses. In general, the inhibition of the biofilm development of LPS-treated Candida spp. was accompanied by a scanty architecture with a reduced numbers of cells compared with the profuse and densely colonized control biofilms. These data are indicative that bacterial LPSs modulate in vitro Candida biofilm formation in a species-specific and time-dependent manner. The clinical and the biological relevance of these findings have yet to be explored. PMID- 20576748 TI - Phylogeographical particularity of the Mycobacterium tuberculosis Beijing family in South Korea based on international comparison with surrounding countries. AB - To understand the domestic population structure of Mycobacterium tuberculosis clinical isolates in the Republic of Korea, we genotypically analysed 80 isolates obtained from various geographical origins in the country. Of these, 64 (80.0 %) isolates were identified as Beijing family strains. It is particularly interesting that their phylogenetic classification, based on the ancient/modern separation and the presence/absence of the genomic region RD181, revealed a majority of the ancient (RD181+) subfamily in the population. The 15 loci of variable number of tandem repeat(s) of mycobacterial interspersed repetitive units (15-MIRU-VNTR) were also analysed. Combination with the previous VNTR data reported from surrounding countries revealed that the topology of the minimum spanning tree was linked tightly not to the geographical origins of the patients but to the phylogenetic characteristics of the isolates. These results show that the phylogeographical distribution of the M. tuberculosis Beijing family around far-eastern Asia could be estimated using international accumulation and comparison of VNTR genotyping data. PMID- 20576749 TI - Clonal spread of CTX-M-15-producing Klebsiella pneumoniae in a Croatian hospital. AB - This study was conducted to detect and analyse the presence of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae associated with a nosocomial outbreak at a Croatian hospital. During 2007, 162 K. pneumoniae isolates with reduced susceptibility to third-generation cephalosporins were collected from various hospital units and patient specimens. Most of the strains were isolated from urine (61 %), followed by blood cultures (13 %), wound swabs (13 %), tracheal aspirates (5 %), intra-abdominal abscess aspirates (4 %), intravascular catheters (3 %) and cerebrospinal fluid (1 %). Medical wards were the most important source of the isolates (46 %); 21 % of the isolates originated from surgical intensive-care units. All patients had infections acquired during their stay in hospital. No community-acquired infections were reported. Sixty of these isolates were chosen for further analysis. A double-disc synergy test (DDST) was used to detect ESBLs. MICs were determined by the broth microdilution method according to CLSI guidelines. The transferability of ceftazidime resistance was tested by conjugation (broth mating method). PCR was used to detect alleles encoding ESBL enzymes. Plasmids encoding ESBLs were extracted with the Macherey Nagel Mini kit according to the manufacturer's recommendations. The genotypes of the strains were compared by analysis of banding patterns generated by PFGE of XbaI-digested genomic DNA. ESBLs were found by DDST in all isolates. All strains were resistant to cefuroxime, ceftazidime, cefotaxime, ceftriaxone, aztreonam, piperacillin/tazobactam and ciprofloxacin. There was variable susceptibility/resistance to cefepime and gentamicin. No resistance to ceftazidime/clavulanate and carbapenems was observed. Only six strains transferred resistance to an Escherichia coli recipient strain, with low frequency. All isolates yielded an amplicon of 545 bp with consensus MA primers. Multiplex PCR was positive for group 1 CTX-M beta-lactamases. Sequencing of selected amplicons revealed the presence of bla(CTX-M-15), with coding regions containing identical nucleotide sequences. Similarly to isolates from India, our isolates contained the ISEcpI insertion sequence located upstream of the bla(CTX M-15) gene, which has recently been demonstrated to mobilize 3'-adjacent genes to transfer between DNA replicons. The isolates contained a large plasmid of approximately 150 kb. The isolates were assigned to five clusters (>85 % similarity), which contained subclusters. The results of this work provided insights into the molecular epidemiology of the spread of ESBLs in K. pneumoniae involved in an outbreak at a Croatian hospital. The hospital antibiotic policy resulted in ceftriaxone being the most heavily prescribed third-generation cephalosporin, which might be expected to select for cefotaximases such as CTX-M 15. PMID- 20576750 TI - Molecular characterization of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates from hospitals in Lithuania. PMID- 20576751 TI - DnaK and GroEL are induced in response to antibiotic and heat shock in Acinetobacter baumannii. AB - We studied the expression of DnaK and GroEL in Acinetobacter baumannii cells (strains ATCC 19606 and RS4) under stress caused by heat shock or antibiotics. A Western blot assay showed that DnaK and GroEL levels increased transiently more than 2-fold after exposure of bacterial cells to heat shock for 20 min at 50 degrees C. Heat induction of DnaK and GroEL was blocked completely when an inhibitor of transcription, rifampicin, was added 1 min before a temperature upshift to 50 degrees C, suggesting that the induction of these chaperones depends on transcription. A. baumannii cells pretreated at 45 degrees C for 30 min were better able to survive at 50 degrees C for 60 min than cells pretreated at 37 degrees C, indicating that A. baumannii is able to acquire thermotolerance. DnaK and GroEL were successfully induced in cells pre-incubated with a subinhibitory concentration of streptomycin. Moreover, bacterial cells pretreated for 30 min at 45 degrees C were better able to survive streptomycin exposure than cells pretreated at physiological temperatures. DnaK expression was upregulated in a multidrug-resistant strain of A. baumannii (RS4) in the presence of different antimicrobials (ampicillin+sulbactam, cefepime, meropenem and sulphamethoxazole+trimethoprim). This study is to the best of our knowledge the first to show that A. baumannii DnaK and GroEL could play an important role in the stress response induced by antibiotics. PMID- 20576752 TI - Aetiological factors contributing to the development of primary laryngeal aspergillosis in immunocompetent patients. AB - Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as part of a systemic infection involving the respiratory system in immunocompromised people. Two cases of laryngeal aspergillosis with no systemic extension and no generalized immune deficiency are presented here. We report what is to the best of our knowledge only the second case of Aspergillus infection in a vocal cord cyst. Aspergillus species were identified in tissue sections and confirmed by PCR studies. We present a literature review of laryngeal aspergillosis cases and discuss predisposing factors, clinical presentation, histopathology, PCR, diagnosis and treatment of Aspergillus laryngitis. The known aetiological causes of the disease are increasing and include iatrogenic factors, vocal abuse, vocal-fold cysts and occupational factors, and immunocompetent patients are susceptible to these predisposing factors. PMID- 20576753 TI - Urinary tract infection caused by nontypable Haemophilus influenzae in the elderly. PMID- 20576754 TI - How close is close enough? Exploring matching criteria in the estimation of recent transmission of tuberculosis. AB - If Mycobacterium tuberculosis isolates from 2 people have the same genotype, transmission may have occurred between them. Genotyping based on the insertion sequence IS6110 uses identical restriction fragment length polymorphisms ("fingerprints") to infer transmission. However, once transmission has occurred, the genotypes may mutate, resulting in divergent fingerprints. Estimation of the proportion of tuberculosis (TB) cases due to recent transmission includes 3 approaches to determine if genotypes match: exact matching (assumes no fingerprint change); band-addition, band-loss, band-shift matching (ad hoc attempt to account for fingerprint changes); and genetic distance (directly accounts for fingerprint changes). Via simulation study, the authors varied the fingerprint change rate, level of recent transmission, and background genetic heterogeneity and estimated sensitivity, specificity, and bias of the recent transmission index by matching method. For exact matching, specificity was always high, but sensitivity decreased as the change rate increased. For band-addition, band-loss, band-shift matching, specificity decreased as genetic diversity decreased, and sensitivity remained high as the change rate increased. Genetic distance offered a compromise between the 2. Results from this study suggest that interpretation of the recent transmission index and the resulting necessary public health interventions will vary according to how researchers account for spontaneous mutation when estimating transmission from genotyping data. PMID- 20576755 TI - Invited commentary: the socioeconomic causes of adverse birth outcomes. AB - Weathering-the cumulative burden of adverse psychosocial and economic circumstances on the bodies of minority women-has been repeatedly described in epidemiologic studies. The most common application has been the documentation of rapidly increasing risks of adverse birth outcomes as African-American women age. Previous work has been based largely on cross-sectional data that aggregate women across a variety of socioeconomic circumstances. When more specific information about women's life-course socioeconomic status is taken into account, however, heterogeneity in the weathering experience of African-American women becomes more readily apparent. Adverse birth outcome risk trajectories with advancing age for African-American women who reside in wealthier neighborhoods look much more similar to those of white women. The accompanying article by Love et al. (Am J Epidemiol. 2010;172(2):127-134) provides a more nuanced investigation of the social conditions that contribute to the weathering of African-American women and points to the critical role played by social and economic conditions over the life course in producing adverse birth outcome disparities. PMID- 20576756 TI - Effect of teenage parenthood on mental health trajectories: does sex matter? AB - Rates of teenage pregnancy and parenthood in the United States remain high. Although many consequences of teenage parenthood have been well studied, little prospective research has examined its effect on mental health. This study aims to better understand the impact of teenage parenthood on mental health and to determine whether sex modifies this relation. Using data from the National Longitudinal Survey of Youth, 1997 (1997-2006), and a matched cohort design, the authors compared changes in the mental health of parenting teenagers and nonparenting teenagers over 6 years of follow-up with mixed-effects regression. The results indicate that mental health improved for all teenagers over 6 years of follow-up. Furthermore, overall, teenage parenthood was not associated with changes in mental health; however, sex modified this relation. Although the mental health of teenage fathers improved at a faster rate compared with nonparenting teenage males, teenage mothers improved at a slower rate compared with nonparenting teenage females. Psychological health has important implications for both the teenage parent and the child. Future studies should aim to better understand the mechanisms through which teenage parenthood impacts mental health among both males and females, and interventions should be developed to ensure mental health among young parents. PMID- 20576757 TI - Exploring weathering: effects of lifelong economic environment and maternal age on low birth weight, small for gestational age, and preterm birth in African American and white women. AB - White women experience their lowest rate of low birth weight (LBW) in their late 20s; the nadir LBW for African-American women is under 20 years with rates rising monotonically thereafter, hypothesized as due to "weathering" or deteriorating health with cumulative disadvantage. Current residential environment affects birth outcomes for all women, but little is known about the impact of early life environment. The authors linked neighborhood income to a transgenerational birth file containing infant and maternal birth data, allowing assessment of economic effects over a woman's life course. African-American women who were born in poorer neighborhoods and were still poor as mothers showed significant weathering with regard to LBW and small for gestational age (SGA) but not preterm birth (PTB). However, African-American women in upper-income areas at both time points had a steady fall in LBW and SGA rate with age, similar to the pattern seen in white women. No group of white women, even those always living in poorer neighborhoods, exhibited weathering with regard to LBW, SGA, or PTB. In contrast, the degree of weathering among African-American women is related to duration of exposure to low-income areas and disappears for those with a life residence in non-poor neighborhoods. PMID- 20576759 TI - Compensatory mutations restore fitness during the evolution of dihydrofolate reductase. AB - Whether a trade-off exists between robustness and evolvability is an important issue for protein evolution. Although traditional viewpoints have assumed that existing functions must be compromised by the evolution of novel activities, recent research has suggested that existing phenotypes can be robust to the evolution of novel protein functions. Enzymes that are targets of antibiotics that are competitive inhibitors must evolve decreased drug affinity while maintaining their function and sustaining growth. Utilizing a transgenic Saccharomyces cerevisiae model expressing the dihydrofolate reductase (DHFR) enzyme from the malarial parasite Plasmodium falciparum, we examine the robustness of growth rate to drug-resistance mutations. We assay the growth rate and resistance of all 48 combinations of 6 DHFR point mutations associated with increased drug resistance in field isolates of the parasite. We observe no consistent relationship between growth rate and resistance phenotypes among the DHFR alleles. The three evolutionary pathways that dominate DHFR evolution show that mutations with increased resistance can compensate for initial declines in growth rate from previously acquired mutations. In other words, resistance mutations that occur later in evolutionary trajectories can compensate for the fitness consequences of earlier mutations. Our results suggest that high levels of resistance may be selected for without necessarily jeopardizing overall fitness. PMID- 20576760 TI - Phylogenetic and biochemical evidence supports the recruitment of an ADP-glucose translocator for the export of photosynthate during plastid endosymbiosis. AB - The acquisition of photosynthesis by eukaryotic cells through enslavement of a cyanobacterium represents one of the most remarkable turning points in the history of life on Earth. In addition to endosymbiotic gene transfer, the acquisition of a protein import apparatus and the coordination of gene expression between host and endosymbiont genomes, the establishment of a metabolic connection was crucial for a functional endosymbiosis. It was previously hypothesized that the first metabolic connection between both partners of endosymbiosis was achieved through insertion of a host-derived metabolite transporter into the cyanobacterial plasma membrane. Reconstruction of starch metabolism in the common ancestor of photosynthetic eukaryotes suggested that adenosine diphosphoglucose (ADP-Glc), a bacterial-specific metabolite, was likely to be the photosynthate, which was exported from the early cyanobiont. However, extant plastid transporters that have evolved from host-derived endomembrane transporters do not transport ADP-Glc but simple phosphorylated sugars in exchange for orthophosphate. We now show that those eukaryotic nucleotide sugar transporters, which define the closest relatives to the common ancestor of extant plastid envelope carbon translocators, possess an innate ability for transporting ADP-Glc. Such an unexpected ability would have been required to establish plastid endosymbiosis. PMID- 20576761 TI - The phylogenetic position of Myxozoa: exploring conflicting signals in phylogenomic and ribosomal data sets. AB - Myxozoans are a diverse group of microscopic endoparasites that have been the focus of much controversy regarding their phylogenetic position. Two dramatically different hypotheses have been put forward regarding the placement of Myxozoa within Metazoa. One hypothesis, supported by ribosomal DNA (rDNA) data, place Myxozoa as a sister taxon to Bilateria. The alternative hypothesis, supported by phylogenomic data and morphology, place Myxozoa within Cnidaria. Here, we investigate these conflicting hypotheses and explore the effects of missing data, model choice, and inference methods, all of which can have an effect in placing highly divergent taxa. In addition, we identify subsets of the data that most influence the placement of Myxozoa and explore their effects by removing them from the data sets. Assembling the largest taxonomic sampling of myxozoans and cnidarians to date, with a comprehensive sampling of other metazoans for 18S and 28S nuclear rDNA sequences, we recover a well-supported placement of Myxozoa as an early diverging clade of Bilateria. By conducting parametric bootstrapping, we find that the bilaterian placement of Buddenbrockia could not alone be explained by long-branch attraction. After trimming a published phylogenomic data set, to circumvent problems of missing data, we recover the myxozoan Buddenbrockia plumatellae as a medusozoan cnidarian. In further explorations of these data sets, we find that removal of just a few identified sites under a maximum likelihood criterion employing the Whelan and Goldman amino acid substitution model changes the placement of Buddenbrockia from within Cnidaria to the alternative hypothesis at the base of Bilateria. Under a Bayesian criterion employing the CAT model, the cnidarian placement is more resilient to data removal, but under one test, a well-supported early diverging bilaterian position for Buddenbrockia is recovered. Our results confirm the existence of two relatively stable placements for myxozoans and demonstrate that conflicting signal exists not only between the two types of data but also within the phylogenomic data set. These analyses underscore the importance of careful model selection, taxon and data sampling, and in-depth data exploration when investigating the phylogenetic placement of highly divergent taxa. PMID- 20576762 TI - More efficient use of donor corneal tissue with Descemet membrane endothelial keratoplasty (DMEK): two lamellar keratoplasty procedures with one donor cornea. PMID- 20576763 TI - Efficacy of topical ciclosporin A for treatment and prevention of graft rejection in corneal grafts with previous rejection episodes. AB - BACKGROUNDS: To evaluate the efficacy of 2% topical ciclosporin A in treating and preventing graft rejection episodes after penetrating keratoplasty (PKP) in patients with a history of graft rejection episodes. METHODS: In this prospective, randomised, double-blind clinical trial, a group of PKP patients were randomly given 2% topical ciclosporin A (group 1) or a placebo (group 2) in addition to a corticosteroid regimen upon an episode of subepithelial or endothelial graft rejection. The topical ciclosporin and placebo were continued for 6 months. The duration of corticosteroid application and the time to resolution of the rejection episode for which ciclosporin or placebo was started, the number of concurrent and subsequent rejection episodes, and the rate of rejection-free survival were compared between the two groups. RESULTS: 22 eyes of 22 patients (12 men) were in group 1 and 21 eyes of 21 patients (10 men) were in group 2. Mean patient age was 32.48 (11.9 years and 35.48 (11.7 years in groups 1 and 2, respectively (p = 0.42). Mean follow-up period was 16.6 (6.1 months and 16.0 (6.3 months (p = 0.75) and the episode for which 2% topical ciclosporin or placebo was started completely resolved after 25.6 (21.0 days and 33.2 (16.7 days in groups 1 and 2, respectively (p = 0.22). The rejection-free graft survival rate was 34.8% in group 1 and 31.7% in group 2 at month 20 (p = 0.89). Conclusion 2% topical ciclosporin A did not add any advantage to conventional corticosteroid treatment in terms of treating and preventing graft rejection in PKP patients with previous history of rejection episodes. PMID- 20576764 TI - High-resolution spectral domain optical coherence tomography features in adult onset foveomacular vitelliform dystrophy. AB - PURPOSE: To describe the different morphological features in adult onset foveomacular vittelliform dystrophy (AOFVD) using high-resolution spectral domain optical coherence tomography (OCT). DESIGN: Prospective observational case series. METHODS: Complete ophthalmologic examination, including spectral domain OCT, was performed in 49 consecutive AOFVD patients (60 eyes). RESULTS: In 28/60 eyes, spectral domain OCT showed hyper-reflective clumps within the outer plexiform and outer nuclear layers. In 9/60 eyes, the photoreceptor inner segment/outer segment (IS/OS) interface appeared highly reflective like a shell all around the vitelliform material, and appeared irregular and discontinued in 27/60 eyes. The Verhoeff membrane was clearly visible at the border of the lesion, disappeared over the vitelliform lesion in 20/60 eyes, became thickened and less defined on the outer aspect of the lesion in 11/60 eyes, appeared without noticeable alterations in 10/60 eyes and not well defined in 19/60 eyes. The vitelliform material appeared as a highly reflective dome-shaped lesion (homogeneous in 14/60 eyes and heterogeneous in 36/60 eyes) located between the photoreceptor layer and the retinal pigment epithelium (RPE). In 10/60 eyes, the macular lesion appeared as hypo/a-reflective. The RPE appeared irregular in 14/60 eyes, with hyper-reflective mottling on its inner aspect. We observed discrete RPE detachments in 29/60 eyes. CONCLUSIONS: We hypothesise that early changes involve the layer between RPE and the IS/OS interface, first with vitelliform material accumulation beneath the sensory retina, and then with IS/OS alterations, pigments migration towards inner layers and fluid accumulation. These changes come with RPE alterations such as hypertrophy or sub-RPE deposits. PMID- 20576765 TI - Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear: long-term results. AB - BACKGROUND: To determine long-term functional and morphological changes after full macular translocation (FMT) with 360 degrees retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF) modulating therapy. METHODS: We retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent FMT with 360 degrees retinotomy between March 2005 and June 2006. Preoperative and postoperative visual acuity, fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were reviewed. RPE tears occurred spontaneously in three cases and after intravitreal triamcinolone in three cases. Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis. RESULTS: Mean postoperative follow-up was 39 months (range 36-50 months). At 12, 24 and 36 months mean visual acuity increased by 6.00 (5.3), 5.57 (5.54) and 6.67 (4.76) lines, respectively. This improvement was maintained at final examination. FA and OCT revealed pigment epithelium atrophy extending to the new fovea in one case only, which also had longer symptom duration. CONCLUSIONS: Long-term follow-up of FMT showed significant improvement in the majority of patients. FMT may be an option for cases of RPE tears of recent onset. Further investigations are necessary to determine FMT's role in tears developing during the course of anti-VEGF therapy. PMID- 20576766 TI - Unexplained vision loss following removal of epiretinal membrane. AB - PURPOSE: To report unexplained severe central vision loss accompanied by a dense central scotoma as an uncommon complication following epiretinal membrane removal. METHODS: Retrospective, multicentred, case series. RESULTS: Six patients underwent uncomplicated vitrectomy surgery between 2000 and 2007 at four separate retina practices for removal of an epiretinal membrane. Preoperative vision ranged from 20/60 to 20/100, with a median of 20/70. On the first day postoperatively, all patients noted decreased vision ranging from counting fingers to light perception and were found to have a dense central scotoma. Posterior segment examination revealed a white, oedematous macula in all affected eyes. Vision improved minimally during the follow-up period, which ranged from 2 months to 5 years. The final vision ranged from 20/200 to hand movements. No anatomic or physiologic cause for the decreased vision and central scotoma was identified. CONCLUSIONS: While uncommon, severe, permanent, central vision loss accompanied by a dense central scotoma can occur following epiretinal membrane removal and should be considered when assessing the risks and benefits of such surgery. PMID- 20576767 TI - Cytomegalovirus anterior uveitis: outcome of treatment. AB - AIM: To determine the outcome of antiviral treatment of cytomegalovirus (CMV) anterior uveitis. METHODS: A retrospective review of patients from Singapore National Eye Centre with CMV anterior uveitis diagnosed by aqueous polymerase chain reaction. Ganciclovir treatment consisted of systemic, topical, intravitreal injections or intravitreal implant. The main outcome measure was resolution of anterior chamber inflammation. RESULTS: 72 eyes of 70 patients were positive for CMV DNA. 35 eyes were treated (23 eyes with acute recurrent anterior uveitis and 12 eyes with chronic anterior uveitis). Eyes that did not respond or recurred with one treatment may receive another course of treatment. There were 47 treatment episodes, 36 (76.6%) of which resulted in a response. However, there were 27 (75.0%) episodes of recurrences after stopping treatment. Systemic and intravitreal ganciclovir and ganciclovir implant had good response rates but also had very high recurrence rates. Ganciclovir gel had moderate response rates, but its recurrence rates were also lower than those of the other modalities. CONCLUSIONS: Ganciclovir gel had lower recurrence rates than the systemic ganciclovir and the implant and should be considered as an option for treatment of CMV anterior uveitis. PMID- 20576768 TI - Decreased susceptibility to quinolones in methicillin-resistant Staphylococcus aureus isolated from ocular infections at a tertiary eye care centre. PMID- 20576769 TI - Influence of the pupil size on visual quality and spherical aberration after implantation of the Tecnis 1-piece intraocular lens. AB - PURPOSE: To evaluate the influence of the pupil size on clinical results and objective parameters of optical quality of the Tecnis 1-piece (ZCB00) intraocular lens. SETTING: Centre of Ophthalmology, Eberhard-Karls University Tubingen, Germany. METHODS: In this study 51 eyes were implanted with a Tecnis 1-piece IOL. Best corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA) were assessed postoperatively. Total spherical aberration and corneal spherical aberration for optical zones of 3, 4, 5 and 6 mm were measured. Contrast sensitivity and depth of focus were evaluated with a 3 mm and 5 mm pinhole (PH). RESULTS: The mean follow-up time was 3.0 +/- 0.4 months. Mean UCVA and BCVA were 20/25 +/- 8 letters and 20/18 +/- 4 letters, respectively. BCVA with both a 3 and a 5 mm PH was 20/18 +/- 4 letters. The corneal spherical aberration was 0.02 +/- 0.01, 0.06 +/- 0.03, 0.14 +/- 0.09 and 0.27 +/- 0.22 for 3, 4, 5 and 6 mm optical zones. Mean total spherical aberration was -0.01 +/- 0.02, 0.0 +/- 0.03, 0.0 +/- 0.06 and 0.0 +/- 0.08 MUm for 3, 4, 5 and 6 mm optical zones, respectively. Contrast sensitivity was not statistically significant different with a 5 mm or 3 mm PH. In addition, the defocus curves with a 3 mm and a 5 mm PH were not statistically significant different. CONCLUSION: The aspheric profile of the Tecnis 1-piece IOL reduces total spherical aberration to virtually zero at all pupil sizes from 3-6 mm. Thus, visual acuity, contrast sensitivity, refraction and defocus curve show the same good results at large pupil sizes compared with small pupil sizes. PMID- 20576770 TI - MRI of the Ex-PRESS stainless steel glaucoma drainage device. AB - AIM: To evaluate the magnetic properties of the Ex-PRESS stainless steel glaucoma drainage device during MRI. DESIGN: Experimental study. METHODS: The Ex-PRESS glaucoma drainage device (316L stainless steel) was examined for magnetic field interactions under standard 1.5, 3.0, and 4.7 T MRI scanning protocols. Testing included measurements of translational and rotational motion of the device induced by static magnetic fields. In addition, the change in the temperature of the device was measured to assess the presence of radiofrequency heating of the stainless steel device. MAIN OUTCOME MEASURES: Degree of angular deflection, device displacement and rotation, and change in temperature. RESULTS: During induced torque testing, displacement did not occur under 1.5 and 3.0 T conditions, although a significant amount of displacement occurred in the 4.7 T environment. Increasing amounts of angular deflection were demonstrated at all three field strengths. We did not record significant temperature changes during brain MRI sequences at any of the three MRI strengths. CONCLUSIONS: The Ex-PRESS glaucoma drainage device, manufactured from grade 316L stainless steel, does move in the presence of high magnetic fields. The clinical significance of this finding and translation to in vivo conditions are not currently known. Further studies are needed to better understand how patients might be affected by the magnetic properties of this device post implantation and how patients should be counselled in regards to safety of MRI in the early and late postoperative period. PMID- 20576772 TI - Contact lens-related microbial keratitis in deployed British military personnel. AB - AIMS: To quantify the effect of contact lens-related microbial keratitis (CLMK) in the British Defence personnel particularly those in active service in the Arabian Gulf and Afghanistan between June 2001 and January 2007. METHODS: A retrospective review of all British military personnel who developed contact lens related keratitis during deployment. RESULTS: A total of 27 cases (27, eyes, 23, male; median age 26 (range 19-41) years) were identified, of whom 19 cases were evacuated from Iraq alone. Twenty cases were associated with soft contact lens wear. Seven cases were culture positive, of which five grew Pseudomonas aeruginosa. The overall incidence of CLMK in contact lens wearer in the British military in Iraq was 35 per 10,000. There was an increased incidence during the summer months. Seventeen eyes (63%) lost more than one line of visual acuity with a resultant permanent medical downgrading in duty capability in nine cases. CONCLUSIONS: CLMK has a poorer outcome in a deployed military environment when compared to the civilian setting. Increased awareness of the health risks of contact lens wear together with standardised treatment regimens based on improved pathogen detection using molecular diagnostics have improved outcomes. PMID- 20576771 TI - Determination of a gene and environment risk model for age-related macular degeneration. AB - BACKGROUND/AIMS: We have recently identified an association between age-related macular degeneration (AMD) and genetic variants in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene. In the current study we interrogated the genomic region in linkage disequilibrium (LD) with the SERPING1 gene, and modelled the contribution to disease of known genetic and environmental AMD risk factors. METHODS: We analysed genes neighbouring SERPING1 and examined haplotype association with AMD. A stepwise logistic regression model was developed including known genetic and environmental risk factors (age, sex and smoking). Individual risk scores were assessed between groups of cases and controls. RESULTS: In SERPING1 region rs2511989 remains most significantly associated (p=1.77*10(-5), OR 0.67). One haplotype, containing the rs2511989 variant and the majority of SERPING1, exhibits marginally stronger association (p=5.13*10(-6), OR 0.66). Our risk model includes six SNPs in CFH, C3, HTRA1 and SERPING1, showing independent effects, which together account for 45% of risk of developing AMD (p=1.65*10(-50)) with a combined population attributable risk of 87%. CONCLUSION: Results implicate SERPING1, with no convincing evidence for involvement of other genes in the region. We demonstrate a multifactorial model with significant differences in risk scores for cases versus controls (p=9.81*10( 71)) and across Age-Related Eye Disease Study (AREDS) score-stratified cases (p=1.88*10(-11)). PMID- 20576773 TI - Fabry disease in children: correlation between ocular manifestations, genotype and systemic clinical severity. AB - BACKGROUND/AIMS: Fabry disease is an X linked lysosomal disorder associated with severe multiorgan failure and premature death. This study aims to determine the prevalence of ophthalmic manifestations in children with the condition and investigate the correlation with genotype and systemic disease severity. METHODS: The records of 26 children from 18 pedigrees with Fabry disease undergoing regular ophthalmic and systemic examination were reviewed. All pedigrees underwent GLA gene sequencing to determine genotype. Correlations between ocular and systemic phenotype and genotype were investigated. RESULTS: Corneal verticillata occurred in 50% of the children in this study (95% CI, 29% to 79%). Children with ophthalmic manifestations were more likely to have loss-of-function GLA mutations (p=0.003). Retinal vascular tortuosity was seen in seven children (27%), all of whom had systemic symptoms suggestive of autonomic neuropathy, such as diarrhoea and syncope. These symptoms seemed less prevalent in children without retinal vascular changes, although this did not reach statistical significance (p=0.134). CONCLUSION: Ophthalmic manifestations of Fabry disease are common even in young children with loss-of-function GLA gene mutations. Although the limited sample size possibly prevented statistical significance, systemic symptoms of autonomic neuropathy often coexist with retinal vascular changes and may share the same pathogenesis. PMID- 20576774 TI - The growing importance of pharmacoeconomics: the case of age-related macular degeneration. PMID- 20576775 TI - Transscleral diode laser cycloablation in patients with good vision. AB - PURPOSE: To investigate the effect of diode laser cyclophotocoagulation for glaucoma on central visual function in patients with good visual acuity (VA). PATIENTS AND METHODS: Patients with preoperative VA 20/60 or better who had undergone cyclodiode treatment according to a standard protocol were evaluated retrospectively. The primary outcome variable was a recorded loss of two or more Snellen lines of best corrected VA during follow-up. Successful intraocular pressure (IOP) control was defined as being between 6 and 21 mmHg inclusive without oral acetazolamide or other glaucoma surgery. RESULTS: 49 eyes of 43 patients with a median pretreatment acuity of 20/30 were included (range 20/16 20/60). After a mean duration of follow-up of 5.0 years, median VA was 20/60 with a line loss of two or more recorded in 15 eyes (30.6%) (mean survival time 7.7 years). 67.3% (33/49) retained VA 20/60 or better, but VA deteriorated by one Snellen line or more in 31 (63.2%), and in 16.3% (8/49), final VA was <20/200. In cases experiencing a two-line loss in acuity, the main causes were glaucoma progression (nine cases) and macula oedema (four cases). Visual loss was unrelated to total treatment dose (mean 99.7 J), initial acuity or initial IOP level. IOP was controlled at final follow-up in 39/49 (79.6%) with no cases of hypotony. CONCLUSIONS: Most of these eyes with difficult to manage glaucoma retained their good VA over long-term follow-up after undergoing diode laser cyclophotocoagulation. The proportion losing two Snellen lines is in line with that reported after trabeculectomy or tube surgery. These results suggest a possible role for the use of transscleral cyclodiode in selected eyes with significant visual potential. Further controlled prospective studies are required to better define this role. PMID- 20576776 TI - The effect of recent amblyopia research on current practice in the UK. AB - BACKGROUND/AIMS: Several studies have recently provided insights into how amblyopia may be most effectively managed. Despite the new evidence, a US study reported that a recent randomised controlled trial had made little influence on clinical practice. The aims of this research are to assess current practice of amblyopia management in the UK and to determine the comparability with the evidence-based recommendations. METHODS: A questionnaire was constructed to assess current amblyopia management practice, particularly in relation to areas investigated by recent research and emailed to every head orthoptist within the UK. RESULTS: There was a great deal of variability in the amount of occlusion that was prescribed for moderate and severe amblyopia. Sixty per cent of clinicians indicated that the maximum they would prescribe was in excess of the 6 h recommended by research. Atropine was rarely recommended as a first-line treatment, with occlusion generally being considered to be more effective. Despite recommendations regarding education as a means of reducing non compliance, only 39% of clinicians always gave written information, although various other methods of enhancing compliance were used. A period of refractive adaptation was allowed by most clinicians but often far less than recommended. CONCLUSION: The uptake of recent research evidence into clinical practice is sporadic and incomplete with one-third of respondents indicating that following the studies, they had made no changes whatsoever to their practice. This is similar to other areas of medicine; the reasons are likely to be varied, and is an area that would benefit from greater attention. PMID- 20576777 TI - Retinal nerve fibre layer evaluation in ocular hypertensive eyes using optical coherence tomography and scanning laser polarimetry in the diagnosis of early glaucomatous defects. AB - AIMS: To evaluate and compare the accuracy of scanning laser polarimetry with variable corneal compensation (GDx-VCC) and optical coherence tomography (OCT) for detecting glaucomatous damage observed in retinal nerve fibre layer (RNFL) monochromatic photographs from ocular hypertensive (OHT) individuals with normal visual fields. METHODS: A total of 181 eyes from 181 patients with intraocular pressure >22 mm Hg were enrolled in a cross-sectional, hospital clinic-based study. All patients underwent full ophthalmological examination, standard automated perimetry, red-free digital RNFL photographs, and RNFL imaging with Stratus OCT and GDx-VCC. Subjects were divided into two groups according to observations from RNFL photographs: 128 OHT subjects without and 53 OHT subjects with RNFL defects. Receiver operating characteristic (ROC) curves plotted for the RNFL parameters were compared between OCT and GDx-VCC. RESULTS: The OCT parameter with the highest diagnostic accuracy for detecting early RNFL defects was average thickness, and for the GDx-VCC was temporal-superior-nasal-inferior-temporal average, with areas under the ROC curve of 0.785 and 0.758, respectively (all AUCs p<0.001). CONCLUSION: OCT and GDx have similar diagnostic accuracy for identifying early defects detected by RNFL monochromatic photography in OHT patients. PMID- 20576778 TI - Clinical features and visual outcomes of Japanese patients with scleritis. AB - PURPOSE: To analyse clinical features, systemic associations, treatment and visual outcomes in Japanese patients with scleritis. METHODS: Clinical records of 83 patients with scleritis who presented between 1998 and 2008 to the Ocular Inflammation Service of the Kyorin Eye Center, Tokyo, were reviewed. RESULTS: Of the 83 patients, 57 (69%) had diffuse anterior scleritis, 9 (11%) had nodular anterior scleritis, 8 (10%) had necrotising anterior scleritis and 9 (11%) had posterior scleritis. There was a slight predominance of women (55%) and unilateral disease (53%). Mean age at presentation was 51 years (range 12 82 years). Secondary ocular complications were observed in 78% of patients, including anterior uveitis in 25% and increased intraocular pressure in 40%. Investigation revealed a systemic disease association in 24 patients (29%), including six patients (7.2%) with tuberculosis and 18 patients (22%) with rheumatologic disease. Thirty-five patients (42%) received systemic corticosteroid treatment and 19 patients (23%) received immunosuppressive agents. All 17 patients with necrotising anterior scleritis or posterior scleritis were treated with oral corticosteroids and/or immunosuppressive drugs. Visual outcomes were generally good; however, poorer outcomes were observed in eyes with necrotising scleritis, mostly due to corneal ulceration or corneal opacification. CONCLUSIONS: A systemic disease association was identified in 29% of Japanese patients with scleritis. Roughly one-half of patients received oral corticosteroids and/or immunosuppressive drugs to control inflammation, with generally good visual outcomes. PMID- 20576779 TI - Modern cataract surgery for radiation-induced cataracts in retinoblastoma. AB - BACKGROUND: Surgery of radiation-induced cataracts in children with retinoblastoma (RB) is a challenge as early intervention is weighted against the need to delay surgery until complete tumour control is obtained. This study analyses the safety and functional results of such surgery. METHODS: In a retrospective, non-comparative, consecutive case series, we reviewed medical records of RB patients <= 14 y of age who underwent either external beam radiotherapy or plaque treatment and were operated for radiation-induced cataract between 1985 and 2008. RESULTS: In total, 21 eyes of 20 RB patients were included and 18 out of the 21 eyes had Reese-Ellsworth stage V or ABC classification group D/E RB. Median interval between last treatment for RB and cataract surgery was 21.5 months, range 3-164 months. Phacoaspiration was performed in 13 eyes (61%), extra-capsular cataract extraction in 8 (39%) and intraocular lens implantation in 19 eyes (90%). The majority of cases, 11/21 (52%), underwent posterior capsulorhexis or capsulotomy and 6/21 (28%) an anterior vitrectomy. Postoperative visual acuity was >= 20/200 in 13 eyes and < 20/200 in 5 eyes. Intraocular tumour recurrence was noted in three eyes. Mean postoperative follow up was 90 months +/ 69 months. CONCLUSIONS: Modern cataract surgery, including clear cornea approach, lens aspiration with posterior capsulotomy, anterior vitrectomy and IOL implantation is a safe procedure for radiation-induced cataract as long as RB is controlled. The visual prognosis is limited by initial tumour involvement of the macula and by corneal complications of radiotherapy. We recommend a minimal interval of 9 months between completion of treatment of retinoblastoma and cataract surgery. PMID- 20576780 TI - Ocular manifestations of torture: solar retinopathy as a result of forced solar gazing. PMID- 20576781 TI - Cerulean fundus: an unexpected complication of cataract surgery in an eye with aqueous misdirection. PMID- 20576782 TI - Prevalence and causes of decreased visual acuity in Singaporean Chinese preschoolers. AB - AIMS: To describe the prevalence and causes of decreased visual acuity (VA) in Singaporean Chinese children. METHODS: A population-based survey of Singaporean Chinese children aged 6 to 72 months was conducted. Participants underwent an orthoptic evaluation, cycloplegic refraction and biometric measurements. A sub group of children aged 30 to 72 months with presenting logMAR VA were included in this analysis. Retesting was performed on the same day or another day by predefined criteria with best refractive correction. Decreased VA was defined as worse than 20/50 (0.4 logMAR) for ages 30 to 47 months and worse than 20/40 (0.3 logMAR) for ages 48 to 72 months. RESULTS: The study examined 3009 children (participation rate 72.3%) of which 2017 children aged 30 to 72 months were eligible for VA testing and completed in 1684 (83.5%). In children aged 30-47 months, the prevalence of decreased presenting VA was 2.1%, and in children 48-72 months, it was 2.05%, with no significant difference between boys and girls in both age groups (p=0.15 and p=0.85). Causes for decreased presenting VA in those 30-47 months were refractive error (7/11, 63.6%), amblyopia (1/11, 9.1%) and "no explanation" (3/11, 27.3%), and 17/24 (70.8%), 5/24 (20.8%) and 2/24 (8.3%), respectively, for those aged 48-72 months. The types of refractive error were astigmatism (15/24, 62.5%), myopia (6/24, 25.0%), hyperopia (2/24, 8.3%) and hyperopia with astigmatism (1/24, 4.2%). CONCLUSIONS: The prevalence of decreased VA among Singaporean Chinese preschoolers is low, with uncorrected refractive error being the main cause in both children 30-47 and 48-72 months. PMID- 20576783 TI - Eye movement recordings to investigate a supranuclear component in chronic progressive external ophthalmoplegia: a cross-sectional study. AB - BACKGROUND: It has been postulated that eye movement disorders in chronic progressive external ophthalmoplegia (CPEO) have a neurological as well as a myopathic component to them. AIM: To investigate whether there is a supranuclear component to eye movement disorders in CPEO using eye movement recordings. METHODS: Saccade and smooth pursuit (SP) characteristics together with vestibulo ocular reflex (VOR) gain and VOR suppression (VORS) gain in 18 patients with CPEO and 34 normal patients were measured using Eyelink II video-oculography. RESULTS: The asymptotic values of the peak velocity main sequence curves were reduced in the CPEO group compared to those of normal patients, with a mean of 161 degrees/s (95% CI 126 degrees/s to 197 degrees/s) compared with 453 degrees/s (95% CI 430 to 475 degrees/s), respectively. Saccadic latency was longer in CPEO (263 ms; 95% CI 250 to 278), compared to controls (185 ms; 95% CI 181 to 189). Smooth pursuit and VOR gains were impaired in CPEO, although this could be explained by non supranuclear causes. VORS gain was identical in the two groups. CONCLUSIONS: This study does not support a supranuclear component to the ophthalmoplegia of CPEO, although the increased latencies observed may warrant further investigation. PMID- 20576784 TI - Recurrent retinal detachment: does initial treatment matter? AB - BACKGROUND/AIMS: To evaluate the treatment course of patients with primary rhegmatogenous retinal detachment (RRD) that re-detach after initial retinal detachment surgery. METHODS: Patients were divided into three groups based on initial surgical treatment: scleral buckle procedure (SBP) (63 eyes), pars plana vitrectomy (PPV) (88 eyes) and combined SBP/PPV (135 eyes). Charts were reviewed for a mean follow-up of 12 months. RESULTS: Average number of secondary procedures to achieve anatomical success was lowest in the SBP group (1.1), compared with the PPV group (1.47) and the SBP/PPV group (1.5) (p<0.05). Patients that re-detached after initial PPV/SBP, PPV or SBP required silicone oil injection in 83%, 60% and 22% of the cases and had final best-corrected visual acuity better than or equal to 20/50 in 21%, 33% and 45% of the cases, respectively. Phakic patients that re-detached after initial treatment with PPV/SBP, PPV and SBP required pars plana lensectomy (PPL) in 42%, 25% and 12.5% of the cases, respectively. CONCLUSION: Patients with primary RRD that re-detach after initial treatment with SBP require fewer number of secondary operations and silicone oil injections, show a trend for better visual outcomes and are less likely to develop dense cataract or to require PPL compared to patients that re detach after initial PPV or PPV/SBP. PMID- 20576785 TI - Prevalence and risk factors for disrupted circadian rhythmicity in children with optic nerve hypoplasia. AB - BACKGROUND/AIMS: Children with optic nerve hypoplasia (ONH) have visual impairment and may have hypopituitarism and developmental delay. Children with ONH have also been reported to have abnormal sleep-wake cycles. We assessed the incidence and nature of sleep-wake abnormalities in children with ONH. METHODS: Rest-activity patterns were assessed in 23 children with ONH using actigraphy, which is a non-invasive method for continuously monitoring activity. The children also had formal assessment of pituitary function, visual acuity measurements, assessment of papillary responsiveness, MRI scans of the head and assessment of neurocognitive function. RESULTS: Sufficient actigraphy data were obtained on 19 of the children. Analysis of expressed rhythmicity revealed normal rest-activity patterns in 13 children (68%). Of the six children (32%) with abnormal rhythmicity, three had fragmented sleep, one had free-running rest-activity cycles and two were arrhythmic. Of the children with normal rhythmicity, the following were found: hypoplastic corpus callosum in 30%, growth hormone deficiency in 53%, hypothyroidism in 23%, adrenal insufficiency in 30%, diabetes insipidus in 0% and developmental delay in 15%. Of the children with abnormal rhythmicity, the following were found: hypoplastic corpus callosum in 66% (p>0.05), severe visual impairment in 100% (p=0.006), abnormal pupillary responsiveness in 85% (p=0.0084), cognitive impairment in 100% (p=0.04) and multiple hormonal deficiencies in 66% (p=0.03). CONCLUSIONS: Abnormal rest activity rhythmicity patterns are present in 30% of children with ONH. The best predictors of abnormal rhythmicity are severe vision impairment, abnormal pupillary responsiveness, developmental delay and multiple hormonal deficiencies. PMID- 20576786 TI - Delayed adjustable sutures: a multicentred clinical review. AB - PURPOSE: To characterise the results of the largest patient series to date undergoing closed conjunctival delayed adjustable suture techniques. METHODS: A multicentre retrospective review of 440 operations (patients aged 10-91 years) by five surgeons at four centres were evaluated for surgical outcomes associated with the delayed adjustable suture technique. RESULTS: 26% (116 of 440) of all patients required postoperative manipulation, with individual surgeon rates ranging from 13% to 56%. The majority of these patients did not complain of diplopia in target gaze and/or had satisfactory cosmetic improvement as evaluated at the 1-3 months follow-up visit (84%). Transient complications included dellen, poor conjunctival appearance, filamentary keratitis, infection, granuloma, exposed suture and corneal abrasion. Serious complications were rare. CONCLUSIONS: This large multicentred series characterises the closed conjunctival delayed adjustable suture technique for the correction of strabismus. It may present some significant advantages to more traditional adjustable suture techniques. PMID- 20576788 TI - Persistent left superior vena cava connected through the left upper pulmonary vein to the left atrium: an unusual pathway for paradoxical embolization and a rare cause of recurrent transient ischaemic attack. AB - Ischaemic stroke, especially in the younger population, is an important cause of morbidity and mortality. When compared with the older population, the underlying aetiology of stroke in the young includes higher rates of cardioembolic disease and congenital heart anomalies. Paradoxical embolism may be an important cause of ischaemic cerebral events, which has to be ruled out in patients with no other evident stroke aetiology. A persistent left superior vena cava (PLSVC) that drains into the left atrium is a very rare congenital anomaly occurring in postnatal life and may be the cause of embolic events such as ischaemic stroke with potentially devastating consequences. For diagnostic purposes, we recommend the use of contrast transthoracic and transesophageal echocardiography with contrast agent application through the left arm peripheral intravenous line, which makes it possible to ascertain the presence of a right-to-left shunt. Computed tomography of the chest is recommended for a PLSVC with atypical left atrial drainage confirmation. Consequent endovascular occlusion of the PLSVC is feasible and can be performed with minimal procedural risk. If this cause of paradoxical embolism is not taken into consideration, the first manifestation of this clinical entity could be underestimated, increasing the likelihood of ischaemic stroke recurrence with potentially disabling or fatal consequences. We report the diagnosis and successful endovascular repair of this anomaly. This case report also aims to highlight the importance of close collaboration between neurologists, cardiologists and radiologists needed for accurate identification of stroke aetiology in young patients. PMID- 20576787 TI - Nitric oxide functions as a signal and acts upstream of AtCaM3 in thermotolerance in Arabidopsis seedlings. AB - To characterize the role of nitric oxide (NO) in the tolerance of Arabidopsis (Arabidopsis thaliana) to heat shock (HS), we investigated the effects of heat on three types of Arabidopsis seedlings: wild type, noa1(rif1) (for nitric oxide associated1/resistant to inhibition by fosmidomycin1) and nia1nia2 (for nitrate reductase [NR]-defective double mutant), which both exhibit reduced endogenous NO levels, and a rescued line of noa1(rif1). After HS treatment, the survival ratios of the mutant seedlings were lower than those of wild type; however, they were partially restored in the rescued line. Treatment of the seedlings with sodium nitroprusside or S-nitroso-N-acetylpenicillamine revealed that internal NO affects heat sensitivity in a concentration-dependent manner. Calmodulin 3 (CaM3) is a key component of HS signaling in Arabidopsis. Real-time reverse transcription-polymerase chain reaction analysis after HS treatment revealed that the AtCaM3 mRNA level was regulated by the internal NO level. Sodium nitroprusside enhanced the survival of the wild-type and noa1(rif1) seedlings; however, no obvious effects were observed for cam3 single or cam3noa1(rif1) double mutant seedlings, suggesting that AtCaM3 is involved in NO signal transduction as a downstream factor. This point was verified by phenotypic analysis and thermotolerance testing using seedlings of three AtCaM3 overexpressing transgenic lines in an noa1(rif1) background. Electrophoretic mobility-shift and western-blot analyses demonstrated that after HS treatment, NO stimulated the DNA-binding activity of HS transcription factors and the accumulation of heat shock protein 18.2 (HSP18.2) through AtCaM3. These data indicate that NO functions in signaling and acts upstream of AtCaM3 in thermotolerance, which is dependent on increased HS transcription factor DNA binding activity and HSP accumulation. PMID- 20576789 TI - Towards hospital standardization in Europe. AB - QUALITY PROBLEM: There is no simple tool to assess compliance with common national and European directives, guidance and professional advice on the management of healthcare institutions. Despite evidence of unacceptable variations in the protection of patient and staff safety little attention has been given to harmonizing the way services are organized and managed. INITIAL ASSESSMENT: Existing systems which define organizational standards, or assess compliance with them, are not in a position to extend this activity into or across national borders in Europe. Certification, accreditation and licensing programmes are too variable to provide a common basis for consistent assessment. Consensual standards would inevitably be minimal if they were to achieve acceptance by all or a majority of member state governments; they would not be standards for excellence or help the majority of organizations to improve performance. PROPOSED SOLUTION: This paper proposes the development of a framework and measurement tool, initially for hospitals, which could be used for self-assessment or peer review to demonstrate compliance with European legislation, guidance and public expectations without infringing national responsibilities. A common code of management practice could be developed through a process similar to that adopted for clinical practice guidelines by the European commission-funded project on appraisal of guidelines research and evaluation. CONCLUSIONS: In practice, the legal relationships between member states and intergovernmental organizations inhibit the harmonization of management practice across-borders. Faster progress to higher levels of performance would be achieved by voluntary, non-regulatory cooperation of enthusiasts to define, measure and improve the quality of healthcare in European hospitals. PMID- 20576791 TI - Meiosis in flowering plants and other green organisms. AB - Sexual eukaryotes generate gametes using a specialized cell division called meiosis that serves both to halve the number of chromosomes and to reshuffle genetic variation present in the parent. The nature and mechanism of the meiotic cell division in plants and its effect on genetic variation are reviewed here. As flowers are the site of meiosis and fertilization in angiosperms, meiotic control will be considered within this developmental context. Finally, we review what is known about the control of meiosis in green algae and non-flowering land plants and discuss evolutionary transitions relating to meiosis that have occurred in the lineages giving rise to the angiosperms. PMID- 20576790 TI - Temperate flowering phenology. AB - Individuals, families, networks, and botanic gardens have made records of flowering times of a wide range of plant species over many years. These data can highlight year to year changes in seasonal events (phenology) and those datasets covering long periods draw interest for their perspective on plant responses to climate change. Temperate flowering phenology is complex, using environmental cues such as temperature and photoperiod to attune flowering to appropriate seasonal conditions. Here we give an overview of flowering phenological recording, outline different patterns of flowering, and look at the interpretation of datasets in relation to seasonal and climatic change. PMID- 20576792 TI - Why members of the public self-test: an interview study. AB - BACKGROUND: A wide range of self-tests are available where contact with a health professional is not necessary. OBJECTIVE: To investigate factors that influenced members of the public to use self-tests. METHODS: Questionnaires, sent to 2335 adults from two general practices in North Birmingham, asked whether recipients had used self-tests and sought consent for contacting them about taking part in an interview. Twenty-three people were interviewed, 20 of whom had used self tests. The interviews were transcribed verbatim, and a thematic analysis was conducted. RESULTS: The findings were organized around two themes. 'Motivations for self-testing' describes the motivating factors surrounding participants' choices to use self-tests. This appeared to be influenced by a number of factors that were organized into four sub-themes: 'diagnosis or speculation', 'perceived benefits of self-testing', 'general attitudes to and experiences of health care' and 'general attitudes to health'. The second theme called 'experience of self testing' describes participants' access to, and use of self-tests, and is split into three sub-themes: 'opportunistic awareness and access', 'use and application' and 'impact on life'. CONCLUSIONS: Overall, self-testing encompasses a broad variety of beliefs and experiences. Some participants saw self-tests as a serious diagnostic tool, whereas others used them out of simple curiosity. Some were motivated by their generally positive attitude to health, but others may have been motivated by negative health care experiences. Some saw self-testing as an empowering process to be proud of, while others seemed to view it as an illegitimate activity that needed to be hidden from professionals. PMID- 20576793 TI - Genetic variation in RNASEL associated with prostate cancer risk and progression. AB - Variation in genes contributing to the host immune response may mediate the relationship between inflammation and prostate carcinogenesis. RNASEL at chromosome 1q25 encodes ribonuclease L, part of the interferon-mediated immune response to viral infection. We therefore investigated the association between variation in RNASEL and prostate cancer risk and progression in a study of 1286 cases and 1264 controls nested within the prospective Physicians' Health Study. Eleven single-nucleotide polymorphisms (SNPs) were selected using the web-based 'Tagger' in the HapMap CEPH panel (Utah residents of Northern and Western European Ancestry). Unconditional logistic regression models assessed the relationship between each SNP and incident advanced stage (T(3)/T(4), T(0) T(4)/M(1) and lethal disease) and high Gleason grade (>/=7) prostate cancer. Further analyses were stratified by calendar year of diagnosis. Cox proportional hazards models examined the relationship between genotype and prostate cancer specific survival. We also explored associations between genotype and serum inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor-alpha receptor 2 using linear regression. Individuals homozygous for the variant allele of rs12757998 had an increased risk of prostate cancer [AA versus GG; odds ratio (OR): 1.63, 95% confidence interval (CI): 1.18-2.25), and more specifically, high-grade tumors (OR: 1.90, 95% CI: 1.25-2.89). The same genotype was associated with increased CRP (P = 0.02) and IL-6 (P = 0.05) levels. Missense mutations R462Q and D541E were associated with an increased risk of advanced stage disease only in the pre-prostate-specific antigen era. There were no significant associations with survival. The results of this study support a link between RNASEL and prostate cancer and suggest that the association may be mediated through inflammation. These novel findings warrant replication in future studies. PMID- 20576794 TI - Significance of serum concentrations of E-selectin and CA19-9 in the prognosis of colorectal cancer. AB - OBJECTIVE: Interaction of CA19-9 with E-selectin is involved in initiation of hematogenous metastases. We investigated whether serum concentrations of E selectin and CA19-9 are good predictors of hematogenous metastases and prognosis in colorectal cancer. METHODS: Pre-operative serum samples were obtained from 152 patients with colorectal cancer, and from 28 healthy volunteers. Correlation between serum E-selectin and CA19-9 was studied in terms of clinically detected hematogenous metastases and prognosis of patients. RESULTS: Low serum concentration of E-selectin was defined as <50 U/ml in healthy volunteers, and on that basis, 20.4% of all patients belonged to the high E-selectin group. Several distinctive characteristics were observed in the clinical course of patients with high serum concentrations of both CA19-9 and E-selectin. The rate of Dukes' D cancer was significantly higher, and curative surgery was performed less frequently in patients with high serum concentrations of both CA19-9 and E selectin (60 and 40%) than in others. However, there was no significant difference in the frequency of recurrence after curative surgery between patients with high serum concentrations of both CA19-9 and E-selectin (25.0%) and others. Overall the 5-year survival rate was significantly lower in patients with high serum concentrations of both CA19-9 and E-selectin (34.3%) than in other patients. Even if the serum concentration of CA19-9 was high, prognosis was not poor in patients with low serum concentration of E-selectin. CONCLUSIONS: These results suggested that it was useful to measure both CA19-9 and E-selectin as markers of hematogenous metastases and as predictors of prognosis in colorectal cancer. PMID- 20576795 TI - Systemically and topically active antinociceptive neurotensin compounds. AB - Neurotensin is a neurotransmitter/modulator with a wide range of actions. Using a series of 10 stable analogs, we have examined neurotensin antinociception in mice. By incorporating (2S)-2-amino-3-(1H-4-indoyl)propanoic acid (l-neoTrp), a series of neurotensin analogs have been synthesized that are stable in serum and are systemically active in vivo. When administered in mice, they all were antinociceptive in the radiant heat tail-flick assay. Time-action curves revealed a peak effect at 30 min and a duration of action ranging from 2 to 4 h. Dose response curves revealed that two compounds were partial agonists with maximal responses below 75%, whereas all of the remaining compounds displayed a full response. Overall, the compounds were quite potent, with ED(50) values similar to those of opioids. At peak effect, the ED(50) values ranged from 0.91 to 9.7 mg/kg s.c. Two of the analogs were active topically. Together, these studies support the potential of neurotensin analogs as analgesics. They are active systemically and by using them topically, it may be possible to avoid problematic side effects, such as hypothermia and hypotension. PMID- 20576796 TI - Effects of hydroxymetabolites of bupropion on nicotine dependence behavior in mice. AB - Bupropion is an atypical antidepressant that also has utility as a smoking cessation aid. Hydroxybupropions are major metabolites of bupropion and are believed to contribute to antidepressant and perhaps smoking cessation activities. Because bupropion metabolism is more similar in humans and mice than in humans and rats, the present study investigated effects of hydroxybupropion enantiomers in mouse behavioral models measuring various aspects of nicotine dependence. Bupropion and (2S,3S)-hydroxybupropion, but not (2R,3R) hydroxybupropion, significantly decreased the development of nicotine reward as measured in the conditioned place preference and withdrawal paradigm in mice. Bupropion and both of its metabolites reversed affective and somatic withdrawal signs in nicotine-dependent mice, but the (2S,3S)-hydroxymetabolite had higher potency. Bupropion and (2S,3S)-, but not (2R,3R)-hydroxybupropion, produced partial substitution for nicotine in drug discrimination tests. Our findings support the hypothesis that the effects of bupropion on measures of nicotine dependence reflect actions of bupropion itself, its hydroxymetabolites, or a combination and suggest that the (2S,3S)-hydroxy isomer is the most active principle, making it a potentially better drug candidate for smoking cessation than bupropion. PMID- 20576797 TI - Excitatory cholinergic and purinergic signaling in bladder are equally susceptible to botulinum neurotoxin a consistent with co-release of transmitters from efferent fibers. AB - Mediators of neuromuscular transmission in rat bladder strips were dissected pharmacologically to examine their susceptibilities to inhibition by botulinum neurotoxins (BoNTs) and elucidate a basis for the clinical effectiveness of BoNT/A in alleviating smooth muscle spasms associated with overactive bladder. BoNT/A, BoNT/C1, or BoNT/E reduced peak and average force of muscle contractions induced by electric field stimulation (EFS) in dose-dependent manners by acting only on neurogenic, tetrodotoxin-sensitive responses. BoNTs that cleaved vesicle associated membrane protein proved to be much less effective. Acetylcholine (ACh) and ATP were found to provide virtually all excitatory input, because EFS-evoked contractions were abolished by the muscarinic receptor antagonist, atropine, combined with either a desensitizing agonist of P2X(1) and P2X(3) or a nonselective ATP receptor antagonist. Both transmitters were released in the innervated muscle layer and, thus, persisted after removal of urothelium. Atropine or a desensitizer of the P2X(1) or P2X(3) receptors did not alter the rate at which muscle contractions were weakened by BoNT/A. Moreover, although cholinergic and purinergic signaling could be partially delineated by using high frequency EFS (which intensified a transient, largely atropine-resistant spike in muscle contractions that was reduced after P2X receptor desensitization), they proved equally susceptible to BoNT/A. Thus, equi-potent blockade of ATP co released with ACh from muscle efferents probably contributes to the effectiveness of BoNT/A in treating bladder overactivity, including nonresponders to anticholinergic drugs. Because purinergic receptors are known mediators of sensory afferent excitation, inhibition of efferent ATP release by BoNT/A could also help to ameliorate acute pain and urgency sensation reported by some recipients. PMID- 20576799 TI - Intrapersonal and interpersonal determinants of smoking status among Asian American adolescents: findings from a national sample. AB - INTRODUCTION: Asian American youth are one of the fastest growing populations in the United States. This present study examined intrapersonal and interpersonal determinants of smoking status among Asian American adolescents. METHODS: Using data from the 2006 National Youth Tobacco Survey, 1,368 Asian American adolescents in Grades 6 through 12 were selected. RESULTS: Findings revealed that one eighth (12%) experimented with cigarettes, 3% smoked occasionally, and 2% smoked regularly. High school students reported higher rates for experimental, occasional, and regular smoking than middle school students. More male than female youth reported the three types of smoking status. Multivariate analyses showed that, compared with nonsmoking, age, weekly income, family members' smoking, refusal of cigarettes from best friends predicted experimental smoking; and positive images of smoking, perception of safety of smoking for only 1 year, awareness of the harmful effects of secondhand smoking, refusal to smoke, and absence from school predicted occasional smoking. Age interacted with refusal to smoke in predicting occasional smoking. Male gender, awareness of the harmful effects of secondhand smoking, refusal to smoke, absence from school, and receptivity to tobacco marketing were determinants of regular smoking. DISCUSSION: This study uniquely examined how the impacts of multiple intrapersonal and interpersonal predictors differed by various stages of smoking in a nationally representative sample of Asian American adolescents. Our findings underscore that smoking treatment and prevention programs should consider predictors of risk for different stages of adolescent smoking. PMID- 20576798 TI - Altered protein kinase C regulation of pulmonary endothelial store- and receptor operated Ca2+ entry after chronic hypoxia. AB - Chronic hypoxia (CH)-induced pulmonary hypertension is associated with decreased basal pulmonary artery endothelial cell (EC) Ca(2+), which correlates with reduced store-operated Ca(2+) (SOC) entry. Protein kinase C (PKC) attenuates SOC entry in ECs. Therefore, we hypothesized that PKC has a greater inhibitory effect on EC SOC and receptor-operated Ca(2+) entry after CH. To test this hypothesis, we assessed SOC in the presence or absence of the nonselective PKC inhibitor GF109203X [2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3 yl)maleimide] in freshly isolated, Fura-2-loaded ECs obtained from intrapulmonary arteries of control and CH rats (4 weeks at 0.5 atm). We found that SOC entry and 1-oleoyl-2-acetyl-sn-glycerol (OAG)- and ATP-induced Ca(2+) influx were attenuated in ECs from CH rats versus controls, and GF109203X restored SOC and OAG responses to the level of controls. In contrast, nonselective PKC inhibition with GF109203X or the selective PKC(epsilon) inhibitor myristoylated V1-2 attenuated ATP-induced Ca(2+) entry in ECs from control but not CH pulmonary arteries. ATP-induced Ca(2+) entry was also attenuated by the T-type voltage gated Ca(2+) channel (VGCC) inhibitor mibefradil in control cells. Consistent with the presence of endothelial T-type VGCC, we observed depolarization-induced Ca(2+) influx in control cells that was inhibited by mibefradil. This response was largely absent in ECs from CH arteries. We conclude that CH enhances PKC dependent inhibition of SOC- and OAG-induced Ca(2+) entry. Furthermore, these data suggest that CH may reduce the ATP-dependent Ca(2+) entry that is mediated, in part, by PKCepsilon and mibefradil-sensitive Ca(2+) channels in control cells. PMID- 20576800 TI - Smoking motives in movies are important for understanding adolescent smoking: a preliminary investigation. AB - INTRODUCTION: Exposure to smoking in movies is strongly associated with smoking uptake and maintenance among adolescents. However, little is known about what features of movies (e.g., the context for smoking or motives for a character smoking) moderate the association between exposure to movie smoking and adolescent smoking. This laboratory study examined whether exposure to movie smoking that is portrayed as having a clear motive is associated with the desire to smoke differently than smoking that is portrayed as having no clear motive. METHODS: A sample of 77 middle school students (mean age of 12.8 years, 62% male, 60% Caucasian) viewed movie clips that portrayed smoking as helping to facilitate social interaction, to relax, to appear rebellious, or as having no clear motive. After exposure to each clip, participants rated their desire to smoke. RESULTS: Exposure to clips where smoking was portrayed as helping characters to relax was associated with a significantly stronger desire to smoke compared with clips where the motive for smoking was unclear. Desire to smoke was similar for clips where no motive was clear, social smoking clips, and rebellious smoking clips. DISCUSSION: These results suggest that the way that smoking is portrayed in movies is important in determining its effect on adolescent smoking. PMID- 20576801 TI - Extracellular superoxide dismutase is a thyroid differentiation marker down regulated in cancer. AB - Reactive oxygen species, specifically hydrogen peroxide (H(2)O(2)), have a significant role in hormone production in thyroid tissue. Although recent studies have demonstrated that dual oxidases are responsible for the H(2)O(2) synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H(2)O(2)-producing enzyme. According to our results, Sod3 is highly expressed in normal thyroid, and becomes even more abundant in rat goiter models. We showed TSH-stimulated expression of Sod3 via phospholipase C-Ca(2+) and cAMP-protein kinase A, a pathway that might be disrupted in thyroid cancer. In line with this finding, we demonstrated an oncogene-dependent decrease in Sod3 mRNA expression synthesis in thyroid cancer cell models that corresponded to a similar decrease in clinical patient samples, suggesting that SOD3 could be used as a differentiation marker in thyroid cancer. Finally, the functional analysis in thyroid models indicated a moderate role for SOD3 in regulating normal thyroid cell proliferation being in line with our previous observations. PMID- 20576804 TI - Blood pressure control in chronic kidney disease: is less really more? AB - BP control is critical in the treatment of patients with chronic kidney disease. Recent guidelines now recommend a BP goal of <130/80 mmHg. Clinical trials using a randomized, intention-to-treat design have not established the benefits of this goal; rather, observational data and secondary or subgroup analyses drove the development of the new guidelines. A variety of observations suggest potential adverse events associate with achieving too low a BP in patients with chronic kidney disease, and ongoing randomized trials will have to establish the benefits or risks of meeting this goal. PMID- 20576802 TI - Novel targets for prostate cancer chemoprevention. AB - Among many endocrine-related cancers, prostate cancer (PCa) is the most frequent male malignancy, and it is the second most common cause of cancer-related death in men in the United States. Therefore, this review focuses on summarizing the knowledge of molecular signaling pathways in PCa because, in order to better design new preventive strategies for the fight against PCa, documentation of the knowledge on the pathogenesis of PCa at the molecular level is very important. Cancer cells are known to have alterations in multiple cellular signaling pathways; indeed, the development and the progression of PCa are known to be caused by the deregulation of several selective signaling pathways such as the androgen receptor, Akt, nuclear factor-kappaB, Wnt, Hedgehog, and Notch. Therefore, strategies targeting these important pathways and their upstream and downstream signaling could be promising for the prevention of PCa progression. In this review, we summarize the current knowledge regarding the alterations in cell signaling pathways during the development and progression of PCa, and document compelling evidence showing that these are the targets of several natural agents against PCa progression and its metastases. PMID- 20576805 TI - A high-powered view of the filtration barrier. AB - Multiphoton excitation fluorescence microscopy is a powerful noninvasive imaging technique for the deep optical sectioning of living tissues. Its application in several intact tissues is a significant advance in our understanding of organ function, including renal pathophysiological mechanisms. The glomerulus, the filtering unit in the kidney, is one good example of a relatively inaccessible and complex structure, with cell types that are otherwise difficult to study at high resolution in their native environment. In this article, we address the application, advantages, and limitations of this imaging technology for the study of the glomerular filtration barrier and the controversy it recently generated regarding the glomerular filtration of macromolecules. More advanced and accurate multiphoton determinations of the glomerular sieving coefficient that are presented here dismiss previous claims on the filtration of nephrotic levels of albumin. The sieving coefficient of 70-kD dextran was found to be around 0.001. Using a model of focal segmental glomerulosclerosis, increased filtration barrier permeability is restricted only to areas of podocyte damage, consistent with the generally accepted role of podocytes and the glomerular origin of albuminuria. Time-lapse imaging provides new details and important in vivo confirmation of the dynamics of podocyte movement, shedding, replacement, and the role of the parietal epithelial cells and Bowman's capsule in the pathology of glomerulosclerosis. PMID- 20576806 TI - TGF-beta receptor deletion in the renal collecting system exacerbates fibrosis. AB - TGF-beta plays a key role in upregulating matrix production in injury-induced renal fibrosis, but how TGF-beta signaling in distinct compartments of the kidney, such as specific segments of the nephron, affects the response to injury is unknown. In this study, we determined the role of TGF-beta signaling both in development of the renal collecting system and in response to injury by selectively deleting the TGF-beta type II receptor in mice at the initiation of ureteric bud development. These mice developed normally but demonstrated a paradoxic increase in fibrosis associated with enhanced levels of active TGF-beta after unilateral ureteral obstruction. Consistent with this observation, TGF-beta type II receptor deletion in cultured collecting duct cells resulted in excessive integrin alphavbeta6-dependent TGF-beta activation that increased collagen synthesis in co-cultured renal interstitial fibroblasts. These results suggest that inhibiting TGF-beta receptor-mediated function in collecting ducts may exacerbate renal fibrosis by enhancing paracrine TGF-beta signaling between epithelial and interstitial cells. PMID- 20576803 TI - Orphan nuclear receptors in breast cancer pathogenesis and therapeutic response. AB - Nuclear receptors comprise a large family of highly conserved transcription factors that regulate many key processes in normal and neoplastic tissues. Most nuclear receptors share a common, highly conserved domain structure that includes a carboxy-terminal ligand-binding domain. However, a subgroup of this gene family is known as the orphan nuclear receptors because to date there are no known natural ligands that regulate their activity. Many of the 25 nuclear receptors classified as orphan play critical roles in embryonic development, metabolism, and the regulation of circadian rhythm. Here, we review the emerging role(s) of orphan nuclear receptors in breast cancer, with a particular focus on two of the estrogen-related receptors (ERRalpha and ERRgamma) and several others implicated in clinical outcome and response or resistance to cytotoxic or endocrine therapies, including the chicken ovalbumin upstream promoter transcription factors, nerve growth factor-induced B, DAX-1, liver receptor homolog-1, and retinoic acid-related orphan receptor alpha. We also propose that a clearer understanding of the function of orphan nuclear receptors in mammary gland development and normal mammary tissues could significantly improve our ability to diagnose, treat, and prevent breast cancer. PMID- 20576807 TI - Intraflagellar transport proteins are essential for cilia formation and for planar cell polarity. AB - The highly conserved intraflagellar transport (IFT) proteins are essential for cilia formation in multiple organisms, but surprisingly, cilia form in multiple zebrafish ift mutants. Here, we detected maternal deposition of ift gene products in zebrafish and found that ciliary assembly occurs only during early developmental stages, supporting the idea that maternal contribution of ift gene products masks the function of IFT proteins during initial development. In addition, the basal bodies in multiciliated cells of the pronephric duct in ift mutants were disorganized, with a pattern suggestive of defective planar cell polarity (PCP). Depletion of pk1, a core PCP component, similarly led to kidney cyst formation and basal body disorganization. Furthermore, we found that multiple ift genes genetically interact with pk1. Taken together, these data suggest that IFT proteins play a conserved role in cilia formation and planar cell polarity in zebrafish. PMID- 20576808 TI - Digoxin associates with mortality in ESRD. AB - The safety of prescribing digoxin in ESRD is unknown. Hypokalemia, which frequently occurs among dialysis patients, may enhance the toxicity of digoxin. Here, we analyzed the association between digoxin prescription and survival in a retrospective cohort using covariate- and propensity score-adjusted Cox models to minimize the potential for confounding by indication. Among 120,864 incident hemodialysis patients, digoxin use associated with a 28% increased risk for death (hazard ratio [HR] 1.28; 95% confidence interval 1.25 to 1.31). Increasing serum digoxin level was also significantly associated with mortality (HR 1.19 per ng/ml increase; 95% confidence interval 1.05 to 1.35). This increased mortality risk with level was most pronounced in patients with lower predialysis serum potassium (K) levels (HR 2.53 [P = 0.01] for K <4.3 mEq/L versus HR 0.86 [P = 0.35] for K >4.6 mEq/L). In conclusion, digoxin use among patients who are on hemodialysis associates with increased mortality, especially among those with low predialysis K concentrations. PMID- 20576810 TI - Influence of left ventricular hypertrophy and geometry on diagnostic accuracy of wall motion and perfusion magnetic resonance during dobutamine stress. AB - BACKGROUND: The purpose of this study was to determine the influence of left ventricular (LV) hypertrophy and geometry on the diagnostic accuracy of wall motion and additional perfusion imaging during high-dose dobutamine/atropine stress magnetic resonance for the detection of coronary artery disease. METHODS AND RESULTS: Combined dobutamine stress magnetic resonance (DSMR)-wall motion and DSMR-perfusion imaging was performed in a single session in 187 patients scheduled for invasive coronary angiography. Patients were classified into 4 categories on the basis of LV mass (normal, <= 81 g/m(2) in men and <= 62 g/m(2) in women) and relative wall thickness (RWT) (normal, <0.45) as follows: normal geometry (normal mass, normal RWT), concentric remodeling (normal mass, increased RWT), concentric hypertrophy (increased mass, increased RWT), and eccentric hypertrophy (increased mass, normal RWT). Wall motion and perfusion images were interpreted sequentially, with observers blinded to other data. Significant coronary artery disease was defined as >= 70% stenosis. In patients with increased LV concentricity (defined by an RWT >= 0.45), sensitivity and accuracy of DSMR-wall motion were significantly reduced (63% and 73%, respectively; P<0.05) compared with patients without increased LV concentricity (90% and 88%, respectively; P<0.05). Although accuracy of DSMR-perfusion was higher than that of DSMR-wall motion in patients with concentric hypertrophy (82% versus 71%; P < 0.05), accuracy of DSMR-wall motion was superior to DSMR-perfusion (90% versus 85%; P < 0.05) in patients with eccentric hypertrophy. CONCLUSIONS: The accuracy of DSMR-wall motion is influenced by LV geometry. In patients with concentric remodeling and concentric hypertrophy, additional first-pass perfusion imaging during high-dose dobutamine stress improves the diagnostic accuracy for the detection of coronary artery disease. PMID- 20576811 TI - Endothelial shear stress: a critical determinant of arterial remodeling and arterial stiffness in humans--a carotid 3.0-T MRI study. AB - BACKGROUND: Low endothelial shear stress (ESS) elicits endothelial dysfunction. However, the relationship between ESS and arterial remodeling and arterial stiffness is unknown in humans. We developed a 3.0-T MRI protocol to evaluate the contribution of ESS to arterial remodeling and stiffness. METHODS AND RESULTS: Fifteen young (aged 26 +/- 3 years) and 15 older (aged 57 +/- 3 years) healthy volunteers as well as 15 patients with cardiovascular disease (aged 63 +/- 10 years) were enrolled. Phase-contrast MRI of the common carotid arteries was used to derive ESS data from the spatial velocity gradients close to the arterial wall. ESS measurements were performed on 3 occasions and showed excellent reproducibility (intraclass correlation coefficient, 0.79). Multiple linear regression analysis accounting for age and blood pressure revealed that ESS was an independent predictor of the following response variables: carotid wall thickness (regression coefficient [b], -0.19 mm(2) per N/m(2); P=0.02), lumen area (b, -15.5 mm(2) per N/m(2); P<0.001), and vessel size (b, -24.0 mm(2) per N/m(2); P<0.001). Segments of the artery wall exposed to lower ESS were significantly thicker than segments exposed to higher ESS within the same artery (P=0.009). Furthermore, ESS was associated with arterial compliance, accounting for age, blood pressure, and wall thickness (b, -0.003 mm(2)/mm Hg per N/m(2); P=0.04). CONCLUSIONS: Our carotid MRI data show that ESS is an important determinant of arterial remodeling and arterial stiffness in humans. The data warrant further studies to evaluate use of carotid ESS as a noninvasive tool to improve the understanding of individual cardiovascular disease risk and to assess novel drug therapies in cardiovascular disease prevention. PMID- 20576809 TI - Anion exchanger 1 interacts with nephrin in podocytes. AB - The central role of the multifunctional protein nephrin within the macromolecular complex forming the glomerular slit diaphragm is well established, but the mechanisms linking the slit diaphragm to the cytoskeleton and to the signaling pathways involved in maintaining the integrity of the glomerular filter remain incompletely understood. Here, we report that nephrin interacts with the bicarbonate/chloride transporter kidney anion exchanger 1 (kAE1), detected by yeast two-hybrid assay and confirmed by immunoprecipitation and co-localization studies. We confirmed low-level glomerular expression of kAE1 in human and mouse kidneys by immunoblotting and immunofluorescence microscopy. We observed less kAE1 in human glomeruli homozygous for the NPHS1(FinMaj) nephrin mutation, whereas kAE1 expression remained unchanged in the collecting duct. We could not detect endogenous kAE1 expression in NPHS1(FinMaj) podocytes in primary culture, but heterologous re-introduction of wild-type nephrin into these podocytes rescued kAE1 expression. In kidneys of Ae1(-/-) mice, nephrin abundance was normal but its distribution was altered along with the reported kAE1-binding protein integrin-linked kinase (ILK). Ae1(-/-) mice had increased albuminuria with glomerular enlargement, mesangial expansion, mesangiosclerosis, and expansion of the glomerular basement membrane. Glomeruli with ILK-deficient podocytes also demonstrated altered AE1 and nephrin expression, further supporting the functional interdependence of these proteins. These data suggest that the podocyte protein kAE1 interacts with nephrin and ILK to maintain the structure and function of the glomerular basement membrane. PMID- 20576812 TI - Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation. AB - The prevailing idea regarding the mechanism(s) by which therapeutic immunosuppressive dendritic cells (DCs) restrain alloimmunity is based on the concept that they interact directly with antidonor T cells, inducing anergy, deletion, and/or regulation. However, this idea has not been tested in vivo. Using prototypic in vitro-generated maturation-resistant (MR) DCs, we demonstrate that once MR-DCs carrying donor antigen (Ag) are administered intravenously, they decrease the direct and indirect pathway T-cell responses and prolong heart allograft survival but fail to directly regulate T cells in vivo. Rather, injected MR-DCs are short-lived and reprocessed by recipient DCs for presentation to indirect pathway CD4(+) T cells, resulting in abortive activation and deletion without detrimental effect on the number of indirect CD4(+) FoxP3(+) T cells, thus increasing the regulatory to effector T cell relative percentage. The effect on the antidonor response was independent of the method used to generate therapeutic DCs or their viability; and in accordance with the idea that recipient Ag-presenting cells mediate the effects of therapeutic DCs in transplantation, prolongation of allograft survival was achieved using donor apoptotic MR-DCs or those lacking surface major histocompatibility complex molecules. We therefore conclude that therapeutic DCs function as Ag-transporting cells rather than Ag-presenting cells to prolong allograft survival. PMID- 20576814 TI - The role of Vdelta2-negative gammadelta T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation. AB - Reactivation of cytomegalovirus (CMV) remains a serious complication after allogeneic stem cell transplantation, but the role of gammadelta T cells is undefined. We have studied the immune reconstitution of Vdelta2negative (Vdelta2neg) gammadelta T cells, including Vdelta1 and Vdelta3 subsets and Vdelta2positive (Vdelta2pos) gammadelta T cells in 40 patients during the first 24 months after stem cell transplantation. Significant long-term expansions of Vdelta2neg but not Vdelta2pos gammadelta T cells were observed during CMV reactivation early after transplantation, suggesting direct involvement of gammadelta T cells in anti-CMV immune responses. Similarly, significantly higher numbers of Vdelta2neg gammadelta T cells were detected in CMV-seropositive healthy persons compared with seronegative donors; the absolute numbers of Vdelta2pos cells were not significantly different. The expansion of Vdelta2neg gammadelta T cells appeared to be CMV-related because it was absent in CMV negative/Epstein-Barr virus-positive patients. T-cell receptor-delta chain determining region 3 spectratyping of Vdelta2neg gammadelta T cells in healthy subjects and patients showed restricted clonality. Polyclonal Vdelta2neg cell lines generated from CMV-seropositive healthy donors and from a recipient of a graft from a CMV-positive donor lysed CMV-infected targets in all cases. Our study shows new evidence for role of gammadelta T cells in the immune response to CMV reactivation in transplantation recipients. PMID- 20576813 TI - Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3 K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. AB - Evidence suggests that tumor microenvironment is critically involved in supporting survival of chronic lymphocytic leukemia (CLL) cells. However, the molecular mechanisms of this effect and the clinical significance are not fully understood. We applied a microenvironment model to explore the interaction between CLL cells and stromal cells and to elucidate the role of phosphatidylinositol 3 kinase (PI3-K)/Akt/phosphatase and tensin homolog detected on chromosome 10 (PTEN) cascade in this process and its in vivo relevance. Primary human stromal cells from bone marrow, lymph nodes, and spleen significantly inhibited spontaneous apoptosis of CLL cells. Pan-PI3-K inhibitors (LY294002, wortmannin, PI-103), isotype-specific inhibitors of p110alpha, p110beta, p110gamma, and small interfering RNA against PI3-K and Akt1 counteracted the antiapoptotic effect of the stromal cells. Induction of apoptosis was associated with a decrease in phosphatidylinositol-3,4,5 triphosphate, PI3-K-p85, and dephosphorylation of phosphatidylinositol-dependent kinase-1 (PDK-1), Akt1, and PTEN. Freshly isolated peripheral blood mononuclear cells from patients with CLL (n = 44) showed significantly higher levels of phosphorylated Akt1, PDK-1, PTEN, and CK2 than healthy persons (n = 8). CK2 inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole, apigenin, and 5,6-dichloro-1 beta-D-ribofuranosylbenzimidazol) decreased phosphorylation of PTEN and Akt, induced apoptosis in CLL cells, and enhanced the response to fludarabine. In conclusion, bone marrow microenvironment modulates the PI3-K/Akt/PTEN cascade and prevents apoptosis of CLL cells. Combined inhibition of PI3-K/Akt and recovery of PTEN activity may represent a novel therapeutic concept for CLL. PMID- 20576815 TI - Somatic ALPS: a FAScinating condition. PMID- 20576816 TI - HLA-DR meets ERK. PMID- 20576817 TI - Making a better antibody: all is not lost. PMID- 20576818 TI - 3D trumps 2D when studying endothelial cells. PMID- 20576820 TI - Roborovskin, a lipocalin in the urine of the Roborovski hamster, Phodopus roborovskii. AB - Many rodents are now known to exhibit an obligate proteinuria that delivers urine mediated chemosignals. In this paper, we explore the urinary proteins of the Roborovski hamster (Phodopus roborovskii). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of urine from individual male and female Roborovski hamsters revealed 2 proteins, with approximate masses of 6 and 17 kDa, the expression pattern of which showed little variation between individuals or between sexes. Peptide mass fingerprints obtained from these 2 proteins revealed a number of features: 1) the proteins of a given mass were the same in all individuals regardless of sex, 2) the 6 kDa protein was not a fragment of the 21 kDa protein, and 3) neither protein was a fragment of a larger, conserved protein such as serum albumin. Electrospray mass spectrometry of purified protein preparations established the mass of the larger protein as invariant, at 17144 +/ 2 Da in all samples. This protein has been termed roborovskin. The primary structure of roborovskin was determined by tandem mass spectrometry of peptides derived from independent and overlapping digestion with 3 proteases, supported by Edman degradation of the protein N-terminus. Roborovskin shared significant homology with olfactory-binding proteins from Myodes glareolus (bank vole) and with aphrodisin and submandibular protein from the golden hamster Mesocricetus auratus, all of which belong to the lipocalin superfamily. Lower levels of homology were also indicated between a variety of other lipocalins including the major urinary proteins from house mice and Norway rats. A model of the tertiary structure of roborovskin was constructed from the primary sequence by homology modeling. This model structure resembled other 8-stranded beta barrel lipocalins. Thus, the Roborovski hamster may demonstrate another variant of urinary lipocalin expression, as for the animals studied here, there appears to be no polymorphism in expression either between sexes or individuals. PMID- 20576821 TI - Long-term treatment with potassium citrate and renal stones in medullary sponge kidney. AB - BACKGROUND AND OBJECTIVES: Medullary sponge kidney (MSK) is a renal malformation typically associated with nephrocalcinosis and recurrent calcium stones. Incomplete distal renal tubular acidosis, hypocitraturia, and hypercalciuria are common. For stone prevention, patients with MSK generally receive the standard "stone clinic" recommendations and often receive potassium citrate (KC). However, the effect on stone recurrence of citrate treatment in these patients has never been studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The issue was retrospectively analyzed on an outpatient basis in 97 patients with a radiologic diagnosis of MSK: 65 had at least one stone risk factor (SRF; hypercalciuria, hypocitraturia, hyperuricosuria, hyperoxaluria) and received KC [29 +/- 8 (SD) mEq/d]; 10 patients with SRF and 22 without received only general stone clinic suggestions. Follow-up was 78 +/- 13, 72 +/- 15, and 83 +/- 14 months, respectively. The 24-hour urinary excretion of calcium, oxalate, uric acid, citrate, and morning urine pH were investigated at baseline and at the end of follow-up. RESULTS: Parallel to a significant rise in urinary citrate and decreased urinary calcium (all P < 0.001), KC led to a dramatic reduction in the stone event rate (from 0.58 to 0.10 stones/yr per patient). The existence of a group of patients with MSK, those without SRF, with a very low stone rate and no SRF was recognized. CONCLUSIONS: Treatment with KC is effective in preventing renal stones in the typical patient with MSK. It seems that two clinical phenotypes among patients showing typical MSK features during radiologic study exist. PMID- 20576822 TI - Fibroblast growth factor 23 and fetuin A are independent predictors for the coronary artery disease extent in mild chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: Cardiovascular disease in chronic kidney disease (CKD) is explained in part by traditional cardiovascular risk factors; by uremia specific factors; and by abnormalities of mineral metabolism, factors involved in its regulation, and in the vascular calcification process. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In an unselected population of 177 patients with calculated GFR (eGFR) between 90 and 30 ml/min per 1.73 m(2), the link between the mineral metabolism abnormalities (calcium, phosphorus, calcium-phosphorus product), regulatory factors (parathyroid hormone [PTH], intact PTH [iPTH], vitamin D, fibroblast growth factor 23 [FGF 23], and fetuin A), and the severity of coronary artery disease (CAD) assessed by coronary angiography were evaluated in three subgroups defined by tertiles of Gensini lesion severity score. RESULTS: The mean serum values for FGF 23 in the entire study population was 28.1 +/- 17.3 RU/ml and for fetuin A was 473.1 +/- 156.2 MUg/ml. Patients with eGFR < 60 ml/min per 1.73 m(2) had significantly higher values of FGF 23 compared with patients with eGFR > 60 ml/min per 1.73 m(2). The Gensini score values significantly correlated with gender; arterial hypertension; and HDL cholesterol, eGFR, iPTH, FGF 23, and fetuin A levels. After the adjustments for traditional and uremia related cardiovascular risk factors, the FGF 23 and fetuin A remained significant predictors of the Gensini score. CONCLUSIONS: This study suggests that in a relatively young population with mild-to-moderate alteration of kidney function and with less traditional cardiovascular risk factors, anomalies of the serum FGF 23 and fetuin A levels appear early in the course of disease and are independent major predictors for extent of CAD. PMID- 20576823 TI - Risk factors associated with patency loss of hemodialysis vascular access within 6 months. AB - BACKGROUND AND OBJECTIVES: Clinical guidelines support vascular access surveillance to detect access dysfunction and alter the clinical course by radiologic or surgical intervention. The objective of this study was to explore the association between loss of primary functional patency within 6 months of first use and demographic and clinical characteristics of patients receiving chronic renal replacement therapy with arteriovenous fistulas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study of all chronic hemodialysis patients followed by the Southern Alberta Renal Program from January 1, 2005 to June 30, 2008. Demographic and clinical variables and initial intra access blood flow (IABF) were compared between those with and without loss of primary functional patency. To determine the contribution of independent variables to the dependant variable of loss of primary functional patency, a multivariable analysis using logistic regression was performed. RESULTS: The incidence of primary failure was 10% (81 of 831). Multivariable analysis found that older age (>65 years, odds ratio [OR] 3.6, P < 0.001), history of diabetes (OR 2.3, P = 0.007), history of smoking (OR 4.3, P < 0.001), presence of forearm fistulas (OR 4.0, P < 0.001), and low initial IABF (<500 ml/min, OR 29, P < 0.001) were independently associated with loss of primary patency. CONCLUSIONS: The set of patient risk factors identified in this study, particularly initial IABF, can be used to identify patients who are most at risk for developing vascular access failure and to guide a more directed approach for a vascular access screening protocol. PMID- 20576824 TI - The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study: objectives, design, and methodology. AB - BACKGROUND AND OBJECTIVES: Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular morbidity and mortality. A systemic arteriopathy and cardiomyopathy has been characterized in pediatric dialysis patients by the presence of morphologic and functional abnormalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Comorbidity in Children with CKD (4C) Study is a multicenter, prospective, observational study aiming to recruit more than 600 children, aged 6 to 17 years, with initial GFR of 10 to 45 ml/min per 1.73 m(2). The prevalence, degree, and progression of cardiovascular comorbidity as well as its association with CKD progression will be explored through longitudinal follow-up. The morphology and function of the heart and large arteries will be monitored by sensitive noninvasive methods and compared with aged-matched healthy controls. Multiple clinical, anthropometric, biochemical, and pharmacologic risk factors will be monitored prospectively and related to the cardiovascular status. A whole-genome association study will be performed to identify common genetic variants associated with progression of cardiovascular alterations and/or renal failure. Monitoring will be continued as patients reach end-stage renal disease and undergo different renal replacement therapies. RESULTS: While cardiovascular morbidity in adults is related to older age and additional risk factor load (e.g., diabetes), the role of CKD-specific factors in the initiation and progression of cardiac and vascular disease are likely to be characterized with greater sensitivity in the pediatric age group. CONCLUSIONS: The 4C study is expected to provide innovative insight into cardiovascular and renal disease progression in CKD. PMID- 20576825 TI - Prevalence and correlates of cognitive impairment in hemodialysis patients: the Frequent Hemodialysis Network trials. AB - BACKGROUND AND OBJECTIVES: Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional analyses were conducted on baseline data collected from 383 subjects participating in the Frequent Hemodialysis Network trials. Global cognitive impairment was defined as a score <80 on the Modified Mini-Mental State Exam, and impaired executive function was defined as a score >or=300 seconds on the Trailmaking B test. Five main categories of explanatory variables were examined: urea clearance, nutritional markers, hemodynamic measures, anemia, and central nervous system (CNS)-active medications. RESULTS: Subjects had a mean age of 51.6 +/- 13.3 years and a median ESRD vintage of 2.6 years. Sixty-one subjects (16%) had global cognitive impairment, and 110 subjects (29%) had impaired executive function. In addition to several nonmodifiable factors, the use of H1-receptor antagonists and opioids were associated with impaired executive function. No strong association was found between several other potentially modifiable factors associated with ESRD and dialysis therapy, such as urea clearance, proxies of dietary protein intake and other nutritional markers, hemodynamic measures, and anemia with global cognition and executive function after adjustment for case-mix factors. CONCLUSIONS: Cognitive impairment, especially impaired executive function, is common among hemodialysis patients, but with the exception of CNS-active medications, is not strongly associated with several ESRD- and dialysis-associated factors. PMID- 20576826 TI - Factors influencing pediatric nephrology trainee entry into the workforce. AB - BACKGROUND AND OBJECTIVES: Emerging needs in pediatric nephrology (PN) have made the number of nephrologists entering the workforce of critical importance. This study aimed to discern factors that influence PN fellows to choose their career path and decide to enter the PN workforce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A survey was sent to the American Society of Pediatric Nephrology list of PN fellows (n = 103) in 2008. The 57 fellows (55%) who completed the survey were representative of the group. RESULTS: The majority decided on a career in PN as senior residents, most commonly due to their interest in renal physiology and academics. They felt residents chose other fields due to lack of interest/exposure to PN, financial constraints, and perceived PN workload. Fellows identified workload and their perception of faculty dissatisfaction as important concerns with PN. None of the respondents planned to leave fellowship, but 21% have considered this. Twenty-eight percent knew a PN fellow who resigned, thought to be due to workload, personal conflicts, and perceived faculty dissatisfaction. CONCLUSIONS: Exposing residents to PN earlier in training and emphasizing positive features may create greater interest in PN. PN programs should be cognizant of workload and the influence of faculty dissatisfaction. Ongoing evaluation of PN fellow perceptions can assist in efforts to enhance recruitment and retention. PMID- 20576827 TI - Effect of kidney disease on acute coronary syndrome. AB - Chronic kidney disease (CKD) is highly prevalent worldwide and is associated with an increased risk for adverse outcomes in patients hospitalized with acute coronary syndrome (ACS). In studies including thousands of patients admitted with myocardial infarction, CKD consistently determines a poorer prognosis for ACS patients. In contrast with CKD, information about the effect of acute kidney injury (AKI) on clinical outcomes after ACS is limited. Most data come from retrospective registry databank studies of nonconsecutive patients with a significant number of patients excluded from analyses. There are no prospective studies designed to determine whether AKI strictly diagnosed by the new the Acute Kidney Injury Network (AKIN) or RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria is a risk factor for death after ACS, and there are no data comparing the RIFLE and AKIN criteria for AKI diagnosis after myocardial infarction. This article reviews the most important data on CKD and ACS and the available data on AKI and ACS. The importance of obtaining an early serum creatinine level after admission for ACS and the importance of renal function monitoring during hospitalization are stressed. PMID- 20576828 TI - Cystatin C as a marker of acute kidney injury in the emergency department. AB - BACKGROUND AND OBJECTIVES: The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, which is a poor marker of early renal dysfunction. The discriminative and predictive abilities of serum and urinary cystatin C were examined for the prediction of AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective cohort study, serum and urinary cystatin C were serially measured in a heterogeneous group of patients (n = 616) presenting to a tertiary care emergency department. The primary outcome was AKI, classified according to RIFLE and AKIN criteria. The secondary outcome was an adjudication based on clinical criteria to AKI, prerenal azotemia, chronic kidney disease (CKD), and normal kidney function. RESULTS: Patients were adjudicated to have AKI in 21.1%, prerenal azotemia in 25.8%, CKD in 2.4%, and normal kidney function in 50.7%. For the diagnosis of AKI, the discriminatory ability of urinary creatinine and cystatin C was marginal. Both serum cystatin C and serum creatinine (at presentation and 6 hours later) showed high discriminatory ability for the diagnosis of AKI. However, only serum cystatin C attained a significant early predictive power (Hosmer-Lemeshow P value > 0.05). Serum cystatin C could differentiate between AKI and prerenal azotemia, but not between AKI and CKD. CONCLUSIONS: Serum cystatin C is an early, predictive biomarker of AKI, which outperforms serum creatinine in the heterogeneous emergency department setting. However, neither biomarker discriminated between AKI and CKD. Additional biomarkers continue to be needed for improved specificity in the diagnosis of community-acquired AKI. PMID- 20576830 TI - Topics in transplantation medicine for general nephrologists. AB - Before transplantation, the general nephrologist is the primary resource for potential kidney transplantation recipients. After transplantation, the general nephrologist is increasingly managing transplant medications and complications. We provide evidence-based management strategies for common clinical issues. Linking our approach with the data allows the clinician to explore each subject in greater depth to tailor care to individual patients. PMID- 20576829 TI - Recruitment and training for home hemodialysis: experience and lessons from the Nocturnal Dialysis Trial. AB - BACKGROUND AND OBJECTIVES: We assessed perceived barriers and incentives to home hemodialysis and evaluated potential correlates with the duration of home hemodialysis training. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Surveys were sent to the principal investigator and study coordinator for each clinical center in the Frequent Hemodialysis Network Nocturnal Trial. Baseline data were obtained on medical comorbidities, cognitive and physical functioning, sessions required for home hemodialysis training, and costs of home renovations. RESULTS: The most commonly perceived barriers included lack of patient motivation, unwillingness to change from in-center modality, and fear of self-cannulation. The most common incentives were greater scheduling flexibility and reduced travel time. The median costs for home renovations varied between $1191 and $4018. The mean number of home hemodialysis training sessions was 27.7 +/- 10.4 (11-59 days). Average training time was less for patients with experience in either self care or both self-care and cannulation. The number of training sessions was unrelated to the score on the Modified Mini Mental Status or Trailmaking B tests or patient's education level. Training time also did not correlate with the SF-36 Physical Function subscale but did with the modified Charlson comorbidity score and older patient age. CONCLUSIONS: Lack of patient or family motivation and fear of the dialysis process are surmountable barriers for accepting home hemodialysis as a modality for renal replacement therapy. Formal education and scores on cognitive function tests are not predictors of training time. PMID- 20576831 TI - Is the effect of angiotensin receptor blockade in patients with heart failure modified by treatment with aspirin? The answer is not so clear! PMID- 20576832 TI - Stem cells in heart failure. PMID- 20576833 TI - Autoantibodies against cardiac troponin I: friend or foe? PMID- 20576834 TI - Loop diuretic therapy in left ventricular systolic dysfunction: has familiarity bred contempt for a critical but potentially nephrotoxic cardio renal therapy? PMID- 20576835 TI - The acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heARt failure: the STAR-heart study. AB - AIMS: Despite accumulated evidence that intracoronary bone marrow cell (BMC) therapy may be beneficial in acute myocardial infarction, there are only limited data available on the effectiveness of BMC's in chronic heart failure. The aim of this study was to quantitatively investigate ventricular haemodynamics, geometry, and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction (LVEF) due to chronic ischaemic cardiomyopathy. METHODS AND RESULTS: Patients with chronic heart failure (n = 391 LVEF 0.05). Plyometric training enhances the muscular tension transmission mainly through a reduction in energy dissipated by the tendon. The lack of changes in the Achilles tendon CSA indicates that changes in mechanical properties would mainly result from a qualitative change in tendinous tissues rather than from changes in the geometry of the Achilles tendon. PMID- 20576841 TI - Chloroform extract of hog barn dust modulates skeletal muscle ryanodine receptor calcium-release channel (RyR1). AB - Skeletal muscle weakness is a reported ailment in individuals working in commercial hog confinement facilities. To date, specific mechanisms responsible for this symptom remain undefined. The purpose of this study was to assess whether hog barn dust (HBD) contains components that are capable of binding to and modulating the activity of type 1 ryanodine receptor Ca2+-release channel (RyR1), a key regulator of skeletal muscle function. HBD collected from confinement facilities in Nebraska were extracted with chloroform, filtered, and rotary evaporated to dryness. Residues were resuspended in hexane-chloroform (20:1) and precipitates, referred to as HBDorg, were air-dried and studied further. In competition assays, HBDorg dose-dependently displaced [3H]ryanodine from binding sites on RyR1 with an IC50 of 1.5+/-0.1 microg/ml (Ki=0.4+/-0.0 microg/ml). In single-channel assays using RyR1 reconstituted into a lipid bilayer, HBDorg exhibited three distinct dose-dependent effects: first it increased the open probability of RyR1 by increasing its gating frequency and dwell time in the open state, then it induced a state of reduced conductance (55% of maximum) that was more likely to occur and persist at positive holding potentials, and finally it irreversibly closed RyR1. In differentiated C2C12 myotubes, addition of HBD triggered a rise in intracellular Ca2+ that was blocked by pretreatment with ryanodine. Since persistent activation and/or closure of RyR1 results in skeletal muscle weakness, these new data suggest that HBD is responsible, at least in part, for the muscle ailment reported by hog confinement workers. PMID- 20576843 TI - Skeletal muscle structural and energetic characteristics in subjects with sickle cell trait, alpha-thalassemia, or dual hemoglobinopathy. AB - Previous studies have shown that subjects with sickle cell trait (SCT), alpha thalassemia (alpha-t), and the dual hemoglobinopathy (SCT/alpha-t) manifest subtle, albeit significant, differences during exercise. To better understand such differences, we assessed skeletal muscle histomorphological and energetic characteristics in 10 control HbAA subjects (C), 5 subjects with alpha-t (alpha t), 6 SCT carriers (SCT) and 9 SCT carriers with alpha-t (SCT/alpha-t). Subjects underwent a muscle biopsy and also performed an incremental maximal exercise and a time to exhaustion test. There were no observable differences in daily energy expenditure, maximal power output (Pmax), or time to exhaustion at 110% Pmax (Tex) among the groups. Blood lactate concentrations measured at the end of the Tex, muscle fiber type distribution, and mean phosphofructokinase (PFK), lactate dehydrogenase (LDH), beta-hydroxyacyl-CoA-dehydrogenase (HAD), and citrate synthase (CS) activities were all similar among the four groups. However, SCT was associated with a lower cytochrome-c oxidase (COx) activity in type IIa fibers (P<0.05), and similar trends were observed in fiber types I and IIx. Trends toward lower creatine kinase (CK) activity (P=0.0702) and higher surface area of type IIx fibers were observed in SCT (P=0.0925). In summary, these findings support most of the previous observations in SCT, such as 1) similar maximal power output and associated maximal oxygen consumption (VO2max) values and 2) lower exercise performances during prolonged submaximal exercise. Furthermore, performances during short supramaximal exercise were not different in SCT. Finally, the dual hemoglobinopathy condition does not seem to affect muscle characteristics. PMID- 20576845 TI - Delayed recovery of velocity-dependent power loss following eccentric actions of the ankle dorsiflexors. AB - Unaccustomed eccentric exercise has been shown to impair muscle function, although little is known regarding this impairment on muscle power. The purpose of this study was to investigate changes in neuromuscular properties of the ankle dorsiflexors during and after an eccentric contraction task and throughout recovery in 21 (10 men, 11 women) recreationally active young adults (25.8+/-2.3 yr). All subjects performed 5 sets of 30 eccentric contractions at 80% of maximum isometric voluntary contraction (MVC) torque. Data were recorded at baseline, during the fatigue task, and for 30 min of recovery. There were no significant sex differences for all fatigue measures; thus data were pooled. After the fatigue task, MVC torque declined by 28% (P<0.05) and did not recover fully, and voluntary activation of the dorsiflexors, as assessed by the interpolated twitch technique, was near maximal (>99%) during and after the fatigue task (P>0.05). Peak twitch torque was reduced by 21% at 2 min of recovery and progressively decreased to 35% by 30 min (P<0.05). Low-frequency torque depression (10-to-50 Hz ratio) was present at 30 s of recovery, increased to 51% by 10 min, and did not recover fully (P<0.05). Velocity-dependent concentric power was reduced by 8% immediately after task termination and did not recover fully within 30 min (P<0.05). The main findings of an incomplete recovery of MVC torque, low frequency torque depression, and shortening velocity indicate the presence of muscle damage, which may have altered excitation-contraction coupling and cross bridge kinetics and reduced the number of functional sarcomeres in series, ultimately leading to velocity-dependent power loss. PMID- 20576844 TI - Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. AB - Mechanical loading can be used to increase bone mass and thus attenuate pathological bone loss. Because the skeleton's adaptive response to loading is most robust before adulthood, elucidating sex-specific responses during growth may help maximize peak bone mass. This study investigated the effect of sex on the response to controlled, in vivo mechanical loading in growing mice. Ten-week old male and female C57Bl/6 mice underwent noninvasive compression of the left tibia. Peak loads of -11.5 N were applied, corresponding to +1,200 microepsilon at the tibial midshaft in both sexes. Cancellous bone mass, architecture, and dynamic formation in the proximal metaphysis were compared between loaded and control limbs via micro-computed tomography and histomorphometry. The strain environment of the proximal metaphysis during loading was characterized using finite element analysis. Both sexes responded to tibial compression through increased bone mass and altered architecture. Cancellous bone mass and tissue density were enhanced in loaded limbs relative to control limbs in both sexes through trabecular thickening and reduced separation. Changes in mass were due to increased cellular activity in loaded limbs compared with control limbs. Adaptation to loading increased the proportion of load transferred by the cancellous bone in the proximal metaphysis. For all cancellous measures, the response to tibial compression did not differ between male and female mice. When similar strains are engendered in males and females, the adaptive response in cancellous bone to mechanical loading does not depend on sex. PMID- 20576847 TI - Mechanical parameters determining pharyngeal collapsibility in patients with sleep apnea. AB - The relative impact of mechanical factors on pharyngeal patency in patients with obstructive sleep apnea is poorly understood. The present study was designed to evaluate parameters of the "tube law" on pharyngeal pressure-flow relationships and collapsibility in patients with obstructive sleep apnea. We developed a mathematical model that considered the collapsible segment of the pharynx to represent an orifice of varying diameter. The model enabled us to assess the effects of pharyngeal compliance (C), neutral cross-sectional area (A(o)), external peripharyngeal pressure (P(ex)), and the resistance proximal to the site of collapse on flow mechanics and pharyngeal collapsibility [critical pressure (P(crit))]. All parameters were measured in 15 patients with obstructive sleep apnea under propofol anesthesia, both at rest and during mandibular advancement and electrical stimulation of the genioglossus. The data was used both to confirm the validity of the model and to compare expected and actual relationships between the tube-law parameters and the pharyngeal pressure-flow relationship and collapsibility. We found a close correlation between predicted and measured P(crit) (R = 0.98), including changes observed during pharyngeal manipulations. C and A(o) were closely and directly interrelated (R = 0.93) and did not correlate with P(crit). A significant correlation was found between P(ex) and P(crit) (R = 0.77; P < 0.01). We conclude that the pharynx of patients with obstructive sleep apnea can be modeled as an orifice with varying diameter. Pharyngeal compliance and A(o) are closely interrelated. Pharyngeal collapsibility depends primarily on the surrounding pressure. PMID- 20576846 TI - Muscle characteristics and altered myofascial force transmission in tenascin-X deficient mice, a mouse model of Ehlers-Danlos syndrome. AB - The Ehlers-Danlos syndrome is a group of inherited connective tissue disorders caused by defects in collagens or tenascin-X (TNX). Muscle involvement can be expected based on interactions between muscle and extracellular matrix molecules; however, muscle function has not yet been investigated quantitatively. This study aims to investigate effects of TNX deficiency on muscular characteristics in TNX knockout (KO) mice, a mouse model of Ehlers-Danlos syndrome. At lower muscle lengths, maximally dissected medial gastrocnemius muscle-tendon complex of TNX KO mice showed lower active force, lower maximal rate of relaxation, and longer time delay between first stimulation pulse and initial force rise, supporting the hypothesis that relatively more slack needs to be taken up, as well as more elastic length changes occurring. In addition, study of the minimally dissected lower leg muscles shows that TNX deficiency strongly affects the mechanical interaction between antagonistic, as well as synergistic, muscles, which is consistent with the concept of altered myofascial force transmission due to increased compliance of myofascial components. Altered properties of the force transmission pathways of muscle (being either part of the myotendinous or myofascial pathways) due to TNX deficiency directly affect muscle function in TNX KO mice. Such effects are likely to contribute to muscle weakness experienced by patients with Ehlers-Danlos syndrome. PMID- 20576848 TI - Simulated rapid warming of abyssal North Pacific waters. AB - Recent observational surveys have shown significant oceanic bottom-water warming. However, the mechanisms causing such warming remain poorly understood, and their time scales are uncertain. Here, we report computer simulations that reveal a fast teleconnection between changes in the surface air-sea heat flux off the Adelie Coast of Antarctica and the bottom-water warming in the North Pacific. In contrast to conventional estimates of a multicentennial time scale, this link is established over only four decades through the action of internal waves. Changes in the heat content of the deep ocean are thus far more sensitive to the air-sea thermal interchanges than previously considered. Our findings require a reassessment of the role of the Southern Ocean in determining the impact of atmospheric warming on deep oceanic waters. PMID- 20576849 TI - Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. AB - Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy. PMID- 20576850 TI - Tissue-engineered lungs for in vivo implantation. AB - Because adult lung tissue has limited regeneration capacity, lung transplantation is the primary therapy for severely damaged lungs. To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix, and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45 to 120 minutes) the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that repopulation of lung matrix is a viable strategy for lung regeneration. PMID- 20576852 TI - Switched magnetospheric regulation of pulsar spin-down. AB - Pulsars are famed for their rotational clocklike stability and their highly repeatable pulse shapes. However, it has long been known that there are unexplained deviations (often termed timing noise) from the rate at which we predict these clocks should run. We show that timing behavior often results from two different spin-down rates. Pulsars switch abruptly between these states, often quasi-periodically, leading to the observed spin-down patterns. We show that for six pulsars the timing noise is correlated with changes in the pulse shape. Many pulsar phenomena, including mode changing, nulling, intermittency, pulse-shape variability, and timing noise, are therefore linked and are caused by changes in the pulsar's magnetosphere. We consider the possibility that high precision monitoring of pulse profiles could lead to the formation of highly stable pulsar clocks. PMID- 20576851 TI - The structure of cbb3 cytochrome oxidase provides insights into proton pumping. AB - The heme-copper oxidases (HCOs) accomplish the key event of aerobic respiration; they couple O2 reduction and transmembrane proton pumping. To gain new insights into the still enigmatic process, we structurally characterized a C-family HCO- essential for the pathogenicity of many bacteria--that differs from the two other HCO families, A and B, that have been structurally analyzed. The x-ray structure of the C-family cbb3 oxidase from Pseudomonas stutzeri at 3.2 angstrom resolution shows an electron supply system different from families A and B. Like family-B HCOs, C HCOs have only one pathway, which conducts protons via an alternative tyrosine-histidine cross-link. Structural differences around hemes b and b3 suggest a different redox-driven proton-pumping mechanism and provide clues to explain the higher activity of family-C HCOs at low oxygen concentrations. PMID- 20576853 TI - Asymmetric density dependence shapes species abundances in a tropical tree community. AB - The factors determining species commonness and rarity are poorly understood, particularly in highly diverse communities. Theory predicts that interactions with neighbors of the same (conspecific) and other (heterospecific) species can influence a species' relative abundance, but empirical tests are lacking. By using a hierarchical model of survival for more than 30,000 seedlings of 180 tropical tree species on Barro Colorado Island, Panama, we tested whether species' sensitivity to neighboring individuals relates to their relative abundance in the community. We found wide variation among species in the effect of conspecific, but not heterospecific, neighbors on survival, and we found a significant relationship between the strength of conspecific neighbor effects and species abundance. Specifically, rare species suffered more from the presence of conspecific neighbors than common species did, suggesting that conspecific density dependence shapes species abundances in diverse communities. PMID- 20576855 TI - The Royal Society's wider role. PMID- 20576856 TI - Gulf oil disaster. Looking beyond the spill, Obama highlights long-term restoration. PMID- 20576854 TI - Innate immune processes are sufficient for driving silicosis in mice. AB - The lung is constantly exposed to potentially pathogenic particles and microorganisms. It has become evident recently that not only innate but also adaptive immune responses to particulates, such as SiO(2) entering the respiratory tract, are complex and dynamic events. Although the cellular mechanisms and anatomical consequences involved in the development of silicosis have been studied extensively, they still remain poorly understood. Based on their capacity for immune regulation, lymphocytes may play a key role in the respiratory response to environmental challenge by SiO(2). The objective of this study was to characterize the impact of SiO(2) exposure on respiratory immune processes, with particular emphasis on evaluating the importance of lymphocytes in the murine silicosis model. Therefore, lymphopenic mice, including NK deficient, Rag1(-/-), or a combination (Rag1(-/-) NK-depleted), were used and demonstrated that SiO(2)-induced fibrosis and inflammation can occur independently of T, B, NK T, and NK cells. Studies in Rag1(-/-) mice suggest further that lymphocytes may participate in the regulation of SiO(2)-induced inflammation through modulation of the Nalp3 inflammasome. This observation may have clinical relevance in the treatment of inflammatory and fibrotic lung diseases that are refractory or respond suboptimally to current therapeutics. PMID- 20576858 TI - Newsmaker interview. Amid war, appraising the mineral wealth of Afghanistan. Interview by Yudhijit Bhattacharjee. PMID- 20576857 TI - Paleoanthropology. Lucy's 'big brother' reveals new facets of her species. PMID- 20576860 TI - Physics. Invisibility cloaks for visible light must remain tiny, theorists predict. PMID- 20576861 TI - Climate change. Critics are far less prominent than supporters. PMID- 20576864 TI - Energy. Natural gas from shale bursts onto the scene. PMID- 20576862 TI - Mantle dynamics. Another quarry sighted in the great mantle plume hunt? PMID- 20576865 TI - Energy. Not under my backyard, thank you. PMID- 20576866 TI - Psychology. A WEIRD view of human nature skews psychologists' studies. PMID- 20576867 TI - Biodiversity. Pushing DAISY. PMID- 20576868 TI - Paleoclimate. Could East Antarctica be headed for big melt? PMID- 20576869 TI - Consequences of legal ivory trade. PMID- 20576870 TI - Benefits of self-reporting. PMID- 20576871 TI - Time for a sea change in Chinese collaboration. PMID- 20576873 TI - Comment on "30,000-year-old wild flax fibers". AB - Kvavadze et al. (Brevia, 11 September 2009, p. 1359) identified fiber samples as 30,000-year-old flax based on a comparison with modern flax fibers analyzed by compound microscope and on the presence of dislocations/nodes in the fibers. We argue that this evidence is not sufficient to identify the fibers as flax. PMID- 20576875 TI - Ecology. Time to tap Africa's livestock genomes. PMID- 20576874 TI - Agriculture. Increased food and ecosystem security via perennial grains. PMID- 20576877 TI - Climate change. Dry times ahead. PMID- 20576876 TI - Medicine. Tackling two diseases with HDL. PMID- 20576878 TI - Biochemistry. Membrane protein gymnastics. PMID- 20576879 TI - Physics. When does photoemission begin? PMID- 20576880 TI - Immunology. IgA changes the rules of memory. PMID- 20576881 TI - SPORE series winner. Resources for anyone interested in the brain. PMID- 20576882 TI - The last glacial termination. AB - A major puzzle of paleoclimatology is why, after a long interval of cooling climate, each late Quaternary ice age ended with a relatively short warming leg called a termination. We here offer a comprehensive hypothesis of how Earth emerged from the last global ice age. A prerequisite was the growth of very large Northern Hemisphere ice sheets, whose subsequent collapse created stadial conditions that disrupted global patterns of ocean and atmospheric circulation. The Southern Hemisphere westerlies shifted poleward during each northern stadial, producing pulses of ocean upwelling and warming that together accounted for much of the termination in the Southern Ocean and Antarctica. Rising atmospheric CO2 during southern upwelling pulses augmented warming during the last termination in both polar hemispheres. PMID- 20576883 TI - Plants integrate information about nutrients and neighbors. AB - Animals regularly integrate information about the location of resources and the presence of competitors, altering their foraging behavior accordingly. We studied the annual plant Abutilon theophrasti to determine whether a plant can demonstrate a similarly complex response to two conditions: presence of a competitor and heterogeneous resource distributions. Individually grown plants fully explored the pot by using a broad and uniform rooting distribution regardless of soil resource distributions. Plants with competitors and uniform soil nutrient distributions exhibited pronounced reductions in rooting breadth and spatial soil segregation among the competing individuals. In contrast, plants with competitors and heterogeneous soil nutrient distributions reduced their root growth only modestly, indicating that plants integrate information about both neighbor and resource distributions in determining their root behavior. PMID- 20576884 TI - Delay in photoemission. AB - Photoemission from atoms is assumed to occur instantly in response to incident radiation and provides the basis for setting the zero of time in clocking atomic scale electron motion. We used attosecond metrology to reveal a delay of 21 +/- 5 attoseconds in the emission of electrons liberated from the 2p orbitals of neon atoms with respect to those released from the 2s orbital by the same 100-electron volt light pulse. Small differences in the timing of photoemission from different quantum states provide a probe for modeling many-electron dynamics. Theoretical models refined with the help of attosecond timing metrology may provide insight into electron correlations and allow the setting of the zero of time in atomic scale chronoscopy with a precision of a few attoseconds. PMID- 20576885 TI - Reconstituting organ-level lung functions on a chip. AB - Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications. PMID- 20576886 TI - 4D electron tomography. AB - Electron tomography provides three-dimensional (3D) imaging of noncrystalline and crystalline equilibrium structures, as well as elemental volume composition, of materials and biological specimens, including those of viruses and cells. We report the development of 4D electron tomography by integrating the fourth dimension (time resolution) with the 3D spatial resolution obtained from a complete tilt series of 2D projections of an object. The different time frames of tomograms constitute a movie of the object in motion, thus enabling studies of nonequilibrium structures and transient processes. The method was demonstrated using carbon nanotubes of a bracelet-like ring structure for which 4D tomograms display different modes of motion, such as breathing and wiggling, with resonance frequencies up to 30 megahertz. Applications can now make use of the full space time range with the nanometer-femtosecond resolution of ultrafast electron tomography. PMID- 20576887 TI - Glass transition dynamics and surface layer mobility in unentangled polystyrene films. AB - Most polymers solidify into a glassy amorphous state, accompanied by a rapid increase in the viscosity when cooled below the glass transition temperature (T(g)). There is an ongoing debate on whether the T(g) changes with decreasing polymer film thickness and on the origin of the changes. We measured the viscosity of unentangled, short-chain polystyrene films on silicon at different temperatures and found that the transition temperature for the viscosity decreases with decreasing film thickness, consistent with the changes in the T(g) of the films observed before. By applying the hydrodynamic equations to the films, the data can be explained by the presence of a highly mobile surface liquid layer, which follows an Arrhenius dynamic and is able to dominate the flow in the thinnest films studied. PMID- 20576889 TI - Detection of hydrated silicates in crustal outcrops in the northern plains of Mars. AB - The composition of the ancient martian crust is a key ingredient in deciphering the environment and evolution of early Mars. We present an analysis of the composition of large craters in the martian northern plains based on data from spaceborne imaging spectrometers. Nine of the craters have excavated assemblages of phyllosilicates from ancient, Noachian crust buried beneath the plains' cover. The phyllosilicates are indistinguishable from those exposed in widespread locations in the southern highlands, demonstrating that liquid water once altered both hemispheres of Mars. PMID- 20576890 TI - Hydrogen isotopes preclude marine hydrate CH4 emissions at the onset of Dansgaard Oeschger events. AB - The causes of past changes in the global methane cycle and especially the role of marine methane hydrate (clathrate) destabilization events are a matter of debate. Here we present evidence from the North Greenland Ice Core Project ice core based on the hydrogen isotopic composition of methane [deltaD(CH4)] that clathrates did not cause atmospheric methane concentration to rise at the onset of Dansgaard Oeschger (DO) events 7 and 8. Box modeling supports boreal wetland emissions as the most likely explanation for the interstadial increase. Moreover, our data show that deltaD(CH4) dropped 500 years before the onset of DO 8, with CH4 concentration rising only slightly. This can be explained by an early climate response of boreal wetlands, which carry the strongly depleted isotopic signature of high-latitude precipitation at that time. PMID- 20576888 TI - The palladium-catalyzed trifluoromethylation of aryl chlorides. AB - The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Here we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and, therefore, should be applicable to late-stage modifications of advanced intermediates. We have also prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process. PMID- 20576891 TI - A generalization of Hamilton's rule for the evolution of microbial cooperation. AB - Hamilton's rule states that cooperation will evolve if the fitness cost to actors is less than the benefit to recipients multiplied by their genetic relatedness. This rule makes many simplifying assumptions, however, and does not accurately describe social evolution in organisms such as microbes where selection is both strong and nonadditive. We derived a generalization of Hamilton's rule and measured its parameters in Myxococcus xanthus bacteria. Nonadditivity made cooperative sporulation remarkably resistant to exploitation by cheater strains. Selection was driven by higher-order moments of population structure, not relatedness. These results provide an empirically testable cooperation principle applicable to both microbes and multicellular organisms and show how nonlinear interactions among cells insulate bacteria against cheaters. PMID- 20576892 TI - Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. AB - The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content. PMID- 20576893 TI - Transition to addiction is associated with a persistent impairment in synaptic plasticity. AB - Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction. PMID- 20576894 TI - Incidental haptic sensations influence social judgments and decisions. AB - Touch is both the first sense to develop and a critical means of information acquisition and environmental manipulation. Physical touch experiences may create an ontological scaffold for the development of intrapersonal and interpersonal conceptual and metaphorical knowledge, as well as a springboard for the application of this knowledge. In six experiments, holding heavy or light clipboards, solving rough or smooth puzzles, and touching hard or soft objects nonconsciously influenced impressions and decisions formed about unrelated people and situations. Among other effects, heavy objects made job candidates appear more important, rough objects made social interactions appear more difficult, and hard objects increased rigidity in negotiations. Basic tactile sensations are thus shown to influence higher social cognitive processing in dimension-specific and metaphor-specific ways. PMID- 20576897 TI - Kogan and Stewart, "Veterinary Professional Associates: does the profession's foresight include a mid-tier professional similar to physician assistant?". PMID- 20576898 TI - Cuba: "the other Caribbean school". PMID- 20576899 TI - A century of veterinary education in Cuba (1907-2007). AB - The development of veterinary education in Cuba has closely mirrored the political changes the nation has undergone. Veterinary studies in Cuba began in 1907, with an emphasis on clinical (individual-animal) medicine. Over time, the professional curriculum has evolved to meet the needs of the nation. Preventive medicine topics were added to the curriculum in 1959. Food-animal production was taught by a separate college until 1990. In 1991, these topics were incorporated into the professional veterinary medical curriculum, and they continue to be an area of emphasis. All veterinary colleges in Cuba follow a centrally organized, student-centered curriculum. A substantial portion of instruction is delivered at educational units, housed on livestock operations, where students participate in extensive field experiences while receiving didactic instruction. The amount of instructional time devoted to hands-on activities increases as students progress through the five-year curriculum. PMID- 20576900 TI - The role of veterinary medicine in an interdisciplinary family health course. AB - First-year students from five health professions colleges engaged in a team taught interdisciplinary family health course located in a community-based setting. This descriptive account of their experiences describes the implications of interdisciplinary education for student learning with an emphasis on the health care concerns of the volunteer families and their companion animals that participated in the Interdisciplinary Family Health course. The authors underscore the potential of interdisciplinary course work for the enrichment of the educational process, with collaboration between veterinary and other health professions, including the disciplines of medicine, nursing, nutrition, pharmacy, physical therapy, dental, social work, and the larger community, by providing an emphasis on family health and companion-animal care. PMID- 20576901 TI - Telephone communication in emergency cases: a training program for veterinary students. AB - The purpose of this project was to evaluate the incorporation of a telephone communication exercise into the junior surgery laboratory at Washington State University. Subjectively, the communication component seemed to encourage greater student preparedness and participation or ownership of cases in the surgical laboratory. Simulated clients were asked to score students on specific tasks and give any specific feedback. Students evaluated themselves on identical material. Areas of communication most likely to result in disparity of scores between the client's evaluation and the student's self-assessment were related to the patient's aftercare. Student survey results were consistently positive in regard to the value of the telephone communications exercise. Communication training in the veterinary curriculum could benefit from identifying opportunities to further integrate client communication experiences into other courses or laboratory experiences. PMID- 20576902 TI - Development and evaluation of a new educational resource for farm-health planning. AB - Simple Templates for Everyday Planning and Support (STEPS) was created to illustrate the dynamic process of farm-health planning. Farm-health planning, also known as herd health or flock health planning, is a holistic, proactive management approach to animal health and welfare. This resource was used in a teaching seminar held for two groups of fourth-year veterinary students over a two-year period. Students answered a questionnaire before and after the teaching seminar that revealed that most participants believed the new resource had increased their knowledge of and ability to undertake farm-health planning. Students also completed one of four species-specific case examples that were evaluated by the first author. Most students (90.7%) included at least half of the essential farm-health planning factors in their case example submission. Twenty-six of these essential health planning factors were included by at least 80% of study participants. Six essential health planning factors received less than 20% of the student response rate. The traditional veterinary skills, which involve the management of individual animals, such as an assessment of the severity of lesions, were well represented in all of the case examples. However, the monitoring step of farm-health planning, such as the use of intervention levels, was the least well answered by the student population. In conclusion, the research study found that the STEPS seminar was successful in introducing many of the main principles of farm-health planning to two groups of fourth-year veterinary students. PMID- 20576903 TI - The effect of differing Audience Response System question types on student attention in the veterinary medical classroom. AB - The purpose of this study was to evaluate the ability of specific types of multiple-choice questions delivered using an Audience Response System (ARS) to maintain student attention in a professional educational setting. Veterinary students (N=324) enrolled in the first three years of the professional curriculum were presented with four different ARS question types (knowledge base, discussion, polling, and psychological investment) and no ARS questions (control) during five lectures presented by 10 instructors in 10 core courses. Toward the end of the lecture, students were polled to determine the relative effectiveness of specific question types. Student participation was high (76.1%+/-2.0), and most students indicated that the system enhanced the lecture (64.4%). Knowledge base and discussion questions resulted in the highest student-reported attention to lecture content. Questions polling students about their experiences resulted in attention rates similar to those without use of ARS technology. Psychological investment questions, based on upcoming lecture content, detracted from student attention. Faculty preparation time for three ARS questions was shorter for knowledge base questions (22.3 min) compared with discussion and psychological investment questions (38.6 min and 34.7 min, respectively). Polling questions required less time to prepare (22.2 min) than discussion questions but were not different from other types. Faculty stated that the investment in preparation time was justified on the basis of the impact on classroom atmosphere. These findings indicate that audience response systems enhance attention and interest during lectures when used to pose questions that require application of an existing knowledge base and allow for peer interaction. PMID- 20576904 TI - Factors affecting track selection by veterinary professional students admitted to the school of veterinary medicine at the University of California, Davis. AB - Factors affecting track selection before admission to the School of Veterinary Medicine at the University of California, Davis, and factors affecting change of tracks after the first two years of the curriculum were investigated by means of a survey of the 118 students of the graduating class of 2009. The student's background experience before admission to the School of Veterinary Medicine and other personal reasons were significant factors affecting small-animal and mixed animal track choices. The student's background experience before admission to the School of Veterinary Medicine was the only significant factor for choosing the zoological track. The most significant factor for students to change their track from the mixed or zoological track to the small-animal track was background experience before admission to the School of Veterinary Medicine. Anticipated increased employment opportunities after graduation was the most significant factor for students to change their track from the mixed- or small-animal track to the zoological track. Other personal reasons was the significant variable for students to change their track from small-animal or zoological to mixed-animal track. Thus, to increase the number of students interested in tracks with lower enrollment, exposure of potential applicants to experience relevant to that track before admission and Admissions Committee selection criteria are likely to increase the odds of students' choosing that track. PMID- 20576905 TI - Social interactions between veterinary medical students and their teachers in an ambulatory clinic setting in Finland. AB - In this study, the social interactions between students and their teachers in an ambulatory clinic setting were investigated using Bales's interaction process analysis framework. Observational data were collected during five small-group sessions. The observations were quantified, and the behaviors of students and teachers were compared statistically. This study demonstrated that the interaction between students and their teachers was for the most part equal and could be characterized as "positively task oriented." The study has implications for veterinary educators wishing to use social psychology frameworks to assess the quality of learning in small-group clinical setting. PMID- 20576906 TI - The importance of cultivating a preference for complexity in veterinarians for effective lifelong learning. AB - Much attention has been paid to the link between students' approaches to study and the quality of their learning. Less attention has been paid to the lifelong learner. We conceptualized a tripartite relationship between three measures of learning preference: conceptions of knowledge (construction and use vs. intake), need for cognition (high vs. low), and approach to study (deep vs. surface) and hypothesized that an individual's profile on these three measures reconceptualized as a preference for complexity versus simplicity-would affect their attitude toward continuing professional development (CPD). A questionnaire was mailed to 2,000 randomly selected, home-practicing UK veterinarians to quantify their learning preferences, motivation to engage in CPD, and perception of barriers to participation and to assess the relationships between these constructs. Analysis of 775 responses (a 38.8% response rate) confirmed our tripartite model of learning and showed that a preference for complexity was negatively correlated with barriers and positively correlated with intrinsic, social, and extrinsic motivating factors, suggesting that all play a role in the continuing education of this group of professionals. A preference for simplicity was negatively correlated with social motivation and positively correlated with barriers. This study demonstrates that approach not only affects the quality of learning but crucially affects motivation to engage in CPD and perception of barriers to lifelong learning. This should emphasize to veterinary educators the importance of fostering a preference for complexity from an early age, both in terms of its immediate benefits (better understanding) and longer-term benefits (continued engagement with learning). PMID- 20576907 TI - Traditional and nontraditional evaluations of student outcomes in a practical final examination of veterinary radiology. AB - The Faculty of Veterinary Medicine at the University of Helsinki recognized the lack of systems to measure the quality of education. At the department level, this meant lack of systems to measure the quality of students' outcomes. The aim of this article was to compare the quality of outcomes of a final examination in veterinary radiology by calculating the correlations between traditional (quantitative scores traditionally given by veterinary teachers) and nontraditional (qualitative Structure of the Observed Learning Outcome, or SOLO, method) grading results. Evaluation of the quality of the questions is also included. The results indicate that SOLO offers criteria for quality evaluation, especially for questions. A correlation of 0.60 (p<0.01) existed between qualitative and quantitative estimations, and a correlation of 0.79 (p<0.01) existed between evaluators, both using traditional scores. Two suggestions for a better system to evaluate quality in the future: First, development of problem solving skills during the learning process should also be assessed. Second, both the scoring of factual correctness of answers (knowledge) and the grammatical structure of an answer and the quality of presentation should be included in the quality evaluation process. PMID- 20576908 TI - Use of alumni and employer surveys for internal quality assurance of the DVM program at the University of Montreal. AB - Annual alumni and employer surveys, initially designed as outcomes assessment tools, were integrated into a new internal quality assurance strategy to improve the doctor of veterinary medicine program at the University of Montreal's Faculte de Medecine Veterinaire. Data collected annually from the classes of 2004-2007 indicated that alumni and their employers were generally satisfied with their level of preparation after one year of professional activity. Specific weaknesses were found in non-technical skills such as communication and resource management. These data were used in support of other forms of feedback to guide curricular reform. PMID- 20576909 TI - Preparing veterinary students for extramural clinical placement training: issues identified and a possible solution. AB - Extramural clinical placement training is an important part of many veterinary degree programs and provides students with valuable learning experiences in private practice, often focusing on the management of typical first-opinion cases. In the United Kingdom, the Royal College of Veterinary Surgeons (RCVS) has a mandatory requirement that students take 26 weeks of clinical placement or extramural studies (EMS) before graduation. However, if students are to maximize their learning opportunities during these placements, it is important that they be adequately prepared. In response to recent topical issues surrounding EMS in the United Kingdom, the current project undertook an iterative consultation process with key stakeholders, including students and placement providers, to identify key issues associated with students attending placements. These findings then informed the development and content of a computer-aided learning (CAL) package titled "The EMS Driving Licence" that aimed to improve the preparation of students for placements. The CAL package included sections covering the main identified areas of concern: Preparation (including what to take), Working With People (staff and clients), Professionalism (including confidentiality), Frequently Asked Questions (from students), and Top Tips (from practitioners). The CAL package was evaluated by students, and feedback was gathered by means of a questionnaire. Students recognized that the content addressed many of their concerns, and all reported that they would recommend the package to others. The CAL package has been made available to all UK veterinary schools and has received backing from the RCVS as part of their current recommendations on EMS to the UK veterinary profession. PMID- 20576910 TI - The role of undergraduate research experiences in producing veterinary scientists. AB - This study retrospectively examined the influence of a science-based, research oriented degree on the career choices of a group of "early emerger" students who had aspired from an early age to become veterinarians but chose instead to pursue an alternative career in veterinary research. This transformation was in large part because of active participation in research, with supervisors acting as role models and mentors. This finding has important implications for teachers and course designers seeking to influence career decision making in both bioveterinary science and professional veterinary programs. PMID- 20576911 TI - Fulbright scholar international teaching and research opportunities for veterinary faculty. AB - The Fulbright program was established by the US Congress to "enable the government of the United States to increase mutual understanding between the people of the United States and the people of other countries." The Core Fulbright Scholar Program sends more than 800 US faculty and administrators to 125 countries to lecture or conduct research around the world each year. Unfortunately, only 28 faculty members from the US veterinary colleges have used Fulbright Scholar opportunities in the last 20 years (1989-2009). Considering recent worldwide events, such as the global dispersion of the Asian strain of highly pathogenic avian influenza and pandemic H1N1 2009 affecting human and animal species, the importance of awareness and education of veterinarians to such global issues is obviously urgent. Therefore, Fulbright scholarships represent an important opportunity to gain experience and bring this time critical information back to fellow faculty and students. Veterinarians who wish to contribute to internationalization of the curricula and their campuses should consider applying for Fulbright Scholar support to launch their career in this pivotal direction. For details about the Fulbright Scholar Program, eligibility, and application procedures, please visit . PMID- 20576912 TI - Electric-bicycle-related injury: a rising traffic injury burden in China. AB - OBJECTIVE: To examine the rising casualty rate related to electric bicycle usage. DESIGN: Analysis of the Hangzhou Police Bureau's data on electric-bicycle-related injuries and deaths. SETTING: Hangzhou, China, 2004-2008. PATIENTS OR SUBJECTS: Electric-bicycle riders. MAIN OUTCOME MEASURE: Electric-bicycle-related casualty rates in Hangzhou from 2004 to 2008. RESULTS: There was a significant average annual increase in electric-bicycle-related casualty rates of 2.7 per 100,000 population (95% CI 1.5 to 3.9, p=0.005). At the same time, overall road traffic and manual-bicycle-related deaths and injuries decreased. CONCLUSION: As it is difficult to ban the use of electric bicycles in China, laws, rules and regulations need to be reinforced and strengthened. New regulations should be created for the safety of electric bicycle riders and others on the road, and mandatory helmet use should be considered. PMID- 20576913 TI - Congenital syphilis: refining newborn evaluation and management in Shenzhen, southern China. AB - INTRODUCTION: Consistent definitions of congenital syphilis are critical for determining true incidences and setting up targets of elimination. This study aimed to assess the evaluation and management of infants at high risk of congenital syphilis with an antenatal syphilis-screening programme in the Shenzhen SEZ and to develop feasible definitions for the detection of congenital syphilis in China. METHODS: A retrospective study was conducted of all standardised records of pregnant women with positive syphilis between 2003 and 2007. Infants at high risk of congenital syphilis were evaluated by laboratory tests at birth and longitudinal follow-up. A screening test-positive congenital syphilis case was defined based on a positive 19S-IgM-FTA-ABS result at birth. Assuming that 19S-IgM-FTA-ABS was the gold standard, the sensitivity and specificity of the ascertainment methods were calculated. RESULTS: During the study period, 1010 live infants were born to women with active syphilis during pregnancy. 19S-IgM-FTA-ABS detected 42 screening-positive congenital syphilis cases and another nine cases were identified by longitudinal follow-up only. Using 19S-IgM-FTA-ABS as the gold standard, 'fourfold rapid plasma reagin (RPR) titres' had the highest sensitivity and specificity compared with the other two follow-up methods. DISCUSSION: 19S-IgM-FTA-ABS makes congenital syphilis case classification simpler and faster for newborns. In areas where 19S-IgM-FTA-ABS is not available, comparing newborn RPR titres with maternal titres can be an alternative method. Meanwhile, positive follow-up results act as treatment indicators for older infants. As congenital syphilis definitions vary over the country, the Shenzhen programme suggested a practical model for surveillance and treatment in areas with or without available 19S-IgM-FTA-ABS testing. PMID- 20576914 TI - Interpopulation variation in HIV testing promptness may introduce bias in HIV incidence estimates using the serologic testing algorithm for recent HIV seroconversion. AB - OBJECTIVES: The serologic testing algorithm for recent HIV seroconversion (STARHS) calculates incidence using the proportion of testers who produce a level of HIV antibody high enough to be detected by ELISA but low enough to suggest recent infection. The validity of STARHS relies on independence between dates of HIV infection and dates of antibody testing. When subjects choose the time of their own test, testing may be motivated by risky behaviour or symptoms of infection and the criterion may not be met. This analysis was conducted to ascertain whether estimates of incidence derived using STARHS were consistent with estimates derived using a method more robust against motivated testing. METHODS: A cohort-based incidence estimator and two STARHS methods were applied to identical populations (n=3821) tested for HIV antibody at publicly funded sites in Seattle. Overall seroincidence estimates, demographically stratified estimates and incidence rate ratios were compared across methods. The proportion of low-antibody testers among HIV-infected individuals was compared with the proportion expected given their testing histories. RESULTS: STARHS estimates generally exceeded cohort-based estimates. Incidence ratios derived using STARHS between demographic strata were not consistent across methods. The proportion of HIV-infected individuals with lower antibody levels exceeded that which would be expected under independence between infection and testing. CONCLUSIONS: Incidence estimates and incidence rate ratios derived using methods that rely on the changing antibody level over the course of HIV infection may be vulnerable to bias when applied to populations who choose the time of their own testing. PMID- 20576915 TI - Transferrin receptor 2 is crucial for iron sensing in human hepatocytes. AB - Hepcidin expression in vivo is regulated in proportion to iron status (i.e., increased by iron loading and decreased in iron deficiency). However, in vitro studies with hepatoma cell lines often show an inverse relationship between iron status and hepcidin expression. Here, we investigated possible molecular mechanisms responsible for the differences in iron sensing between hepatoma cell lines and human primary hepatocytes. RNA was collected from primary human hepatocytes, and HepG2 and HuH7 hepatoma cells were treated with either transferrin-bound and non-transferrin-bound iron. Expression of hepcidin, transferrin receptor 2, HFE, and hemojuvelin were quantified by real-time PCR. Hepcidin expression was increased in primary human hepatocytes following 24-h exposure to holoferric transferrin. In contrast, hepcidin mRNA levels in hepatoma cells were decreased by transferrin. Hepcidin expression was positively correlated with transferrin receptor 2 mRNA levels in primary human hepatocytes. Compared with primary hepatocytes, transferrin receptor 2 expression was significantly lower in hepatoma cell lines; furthermore, there was no correlation between transferrin receptor 2 and hepcidin mRNA levels in either HepG2 or HuH7 cells. Taken together our data suggest that transferrin receptor 2 is a likely candidate to explain the differences in iron sensing between hepatoma cell lines and primary human hepatocytes. PMID- 20576916 TI - The {omega}-3 fatty acid eicosapentaenoic acid elicits cAMP generation in colonic epithelial cells via a "store-operated" mechanism. AB - Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid abundant in fish oil that exerts a wide spectrum of documented beneficial health effects in humans. Because dietary interventions are relatively inexpensive and are widely assumed to be safe, they have broad public appeal. Their endorsement can potentially have a major impact on human health, but hard mechanistic evidence that specifies how these derivatives work at the cellular level is limited. EPA (50 microM) caused a small elevation of cytoplasmic Ca(2+) concentration ([Ca(2+)]) in intact NCM460 human colonic epithelial cells as measured by fura 2 and a profound drop of [Ca(2+)] within the endoplasmic reticulum (ER) of permeabilized cells as monitored by compartmentalized mag-fura 2. Total internal reflection fluorescence microscopy showed that this loss of ER store [Ca(2+)] led to translocation of the ER-resident transmembrane Ca(2+) sensor STIM1. Using sensitive FRET-based sensors for cAMP in single cells, we further found that EPA caused a substantial increase in cellular cAMP concentration, a large fraction of which was dependent on the drop in ER [Ca(2+)], but independent of cytosolic Ca(2+). An additional component of the EPA-induced cAMP signal was sensitive to the phosphodiesterase inhibitor isobutyl methylxanthine. We conclude that EPA slowly releases ER Ca(2+) stores, resulting in the generation of cAMP. The elevated cAMP is apparently independent of classical G protein-coupled receptor activation and is likely the consequence of a newly described "store-operated" cAMP signaling pathway that is mediated by STIM1. PMID- 20576917 TI - Inactivation of hepatocyte nuclear factor-4{alpha} mediates alcohol-induced downregulation of intestinal tight junction proteins. AB - Chronic alcohol exposure has been shown to increase the gut permeability in the distal intestine, in part, through induction of zinc deficiency. The present study evaluated the molecular mechanisms whereby zinc deficiency mediates alcohol induced intestinal barrier dysfunction. Examination of zinc finger transcription factors in the gastrointestinal tract of mice revealed a prominent distribution of hepatocyte nuclear factor-4alpha (HNF-4alpha). HNF-4alpha exclusively localizes in the epithelial nuclei and exhibited an increased abundance in mRNA and protein levels in the distal intestine. Chronic alcohol exposure to mice repressed the HNF-4alpha gene expression in the ileum and reduced the protein level and DNA binding activity of HNF-4alpha in all of the intestinal segments with the most remarkable changes in the ileum. Chronic alcohol exposure also decreased the mRNA levels of tight junction proteins, particularly in the ileum. Caco-2 cell culture studies were conducted to determine the role of HNF-4alpha in regulation of the epithelial tight junction and barrier function. Knockdown of HNF-4alpha in Caco-2 cells decreased the mRNA and protein levels of tight junction proteins in association with disruption of the epithelial barrier. Alcohol treatment inactivated HNF-4alpha, which was prevented by N-acetyl cysteine or zinc. The link between zinc and HNF-4alpha function was confirmed by zinc deprivation, which inhibited HNF-4alpha DNA binding activity. These results indicate that inactivation of HNF-4alpha due to oxidative stress and zinc deficiency is likely a novel mechanism contributing to the deleterious effects of alcohol on the tight junctions and the intestinal barrier function. PMID- 20576918 TI - Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts. AB - Biliary epithelial cells (BEC) are morphologically and functionally heterogeneous. To investigate the molecular mechanism for their diversities, we test the hypothesis that large and small BEC have disparity in their target gene response to their transcriptional regulator, the biliary cell-enriched hepatocyte nuclear factor HNF6. The expression of the major HNF (HNF6, OC2, HNF1b, HNF1a, HNF4a, C/EBPb, and Foxa2) and representative biliary transport target genes that are HNF dependent were compared between SV40-transformed BEC derived from large (SV40LG) and small (SV40SM) ducts, before and after treatment with recombinant adenoviral vectors expressing HNF6 (AdHNF6) or control LacZ cDNA (AdLacZ). Large and small BEC were isolated from mouse liver treated with growth hormone, a known transcriptional activator of HNF6, and the effects on selected target genes were examined. Constitutive Foxa2, HNF1a, and HNF4a gene expression were 2.3-, 12.4-, and 2.6-fold, respectively, higher in SV40SM cells. This was associated with 2.7- and 4-fold higher baseline expression of HNF1a- and HNF4a-regulated ntcp and oatp1 genes, respectively. Following AdHNF6 infection, HNF6 gene expression was 1.4-fold higher (P = 0.02) in AdHNF6 SV40SM relative to AdHNF6 SV40LG cells, with a corresponding higher Foxa2 (4-fold), HNF1a (15-fold), and HNF4a (6-fold) gene expression in AdHNF6-SV40SM over AdHNF6-SV40LG. The net effects were upregulation of HNF6 target gene glucokinase and of Foxa2, HNF1a, and HNF4a target genes oatp1, ntcp, and mrp2 over AdLacZ control in both cells, but with higher levels in AdH6-SV40SM over AdH6-SV40LG of glucokinase, oatp1, ntcp, and mrp2 (by 1.8-, 3.4-, 2.4-, and 2.5-fold, respectively). In vivo, growth hormone-mediated increase in HNF6 expression was associated with similar higher upregulation of glucokinase and mrp2 in cholangiocytes from small vs. large BEC. Small and large BEC have a distinct profile of hepatocyte transcription factor and cognate target gene expression, as well as differential strength of response to transcriptional regulation, thus providing a potential molecular basis for their divergent function. PMID- 20576919 TI - Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons. AB - This study examined whether bacterial cell products that might gain access to the intestinal interstitium could activate mouse colonic nociceptive dorsal root ganglion (DRG) neurons using molecular and electrophysiological recording techniques. Colonic projecting neurons were identified by using the retrograde tracer fast blue and Toll-like receptor (TLR) 1, 2, 3, 4, 5, 6, 9, adapter proteins Md-1 and Md-2, and MYD88 mRNA expression was observed in laser-captured fast blue-labeled neurons. Ultrapure LPS 1 microg/ml phosphorylated p65 NF-kappaB subunits increased transcript for TNF-alpha and IL-1beta and stimulated secretion of TNF-alpha from acutely dissociated DRG neurons. In current-clamp recordings from colonic DRG neurons, chronic incubation (24 h) of ultrapure LPS significantly increased neuronal excitability. In acute studies, 3-min superfusion of standard-grade LPS (3-30 microg/ml) reduced the rheobase by up to 40% and doubled action potential discharge rate. The LPS effects were not significantly different in TLR4 knockout mice compared with wild-type mice. In contrast to standard-grade LPS, acute application of ultrapure LPS did not increase neuronal excitability in whole cell recordings or afferent nerve recordings from colonic mesenteric nerves. However, acute application of bacterial lysate (Escherichia coli NLM28) increased action potential discharge over 60% compared with control medium. Moreover, lysate also activated afferent discharge from colonic mesenteric nerves, and this was significantly increased in chronic dextran sulfate sodium salt mice. These data demonstrate that bacterial cell products can directly activate colonic DRG neurons leading to production of inflammatory cytokines by neurons and increased excitability. Standard-grade LPS may also have actions independent of TLR signaling. PMID- 20576920 TI - Acid-induced p16 hypermethylation contributes to development of esophageal adenocarcinoma via activation of NADPH oxidase NOX5-S. AB - Inactivation of tumor suppressor gene p16 may play an important role in the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). Hypermethylation of p16 gene promoter is an important mechanism inactivating p16. However, the mechanisms of p16 hypermethylation in EA are not known. Therefore, we examined whether acid increases methylation of p16 gene promoter and whether NADPH oxidase NOX5-S mediates acid-induced p16 hypermethylation in a Barrett's cell line BAR-T and an EA cell line OE33. We found that NOX5-S was present in BAR T and OE33 cells. Acid-induced increase in H(2)O(2) production and cell proliferation was significantly reduced by knockdown of NOX5-S. Exogenous H(2)O(2) remarkably increased p16 promoter methylation and cell proliferation. In addition, acid treatment significantly increased p16 promoter methylation and decreased p16 mRNA level. Knockdown of NOX5-S significantly increased p16 mRNA, inhibited acid-induced downregulation of p16 mRNA, and blocked acid-induced increase in p16 methylation and cell proliferation. Conversely, overexpression of NOX5-S significantly decreased p16 mRNA and increased p16 methylation and cell proliferation. In conclusion, NOX5-S is present in BAR-T cells and OE33 cells and mediates acid-induced H(2)O(2) production and cell proliferation. NOX5-S is also involved in acid-induced hypermethylation of p16 gene promoter and downregulation of p16 mRNA. It is possible that acid reflux present in BE patients may activate NOX5-S and increase production of reactive oxygen species, which in turn increase p16 promoter methylation, downregulate p16 expression, and increase cell proliferation, thereby contributing to the progression from BE to EA. PMID- 20576921 TI - Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury. AB - The liver is susceptible to such oxidative and metabolic stresses as ischemia reperfusion (I/R) and fatty acid accumulation. Probiotics are viable microorganisms that restore the gut microbiota and exert a beneficial effect on the liver by inhibiting bacterial enzymes, stimulating immunity, and protecting intestinal permeability. We evaluated Lactobacillus paracasei F19 (LP-F19), for its potential protective effect, in an experimental model of I/R (30 min ischemia and 60 min reperfusion) in rats fed a standard diet or a steatogen [methionine/choline-deficient (MCD)] diet. Both groups consisted of 7 sham operated rats, 10 rats that underwent I/R, and 10 that underwent I/R plus 8 wk of probiotic dietary supplementation. In rats fed a standard diet, I/R induced a decrease in sinusoid perfusion (P < 0.001), severe liver inflammation, and necrosis besides an increase of tissue levels of malondialdehyde (P < 0.001), tumor necrosis factor-alpha (P < 0.001), interleukin (IL)-1beta (P < 0.001), and IL-6 (P < 0.001) and of serum levels of transaminase (P < 0.001) and lipopolysaccharides (P < 0.001) vs. sham-operated rats. I/R also induced a decrease in Bacterioides, Bifidobacterium, and Lactobacillus spps (P < 0.01, P < 0.001, and P < 0.001, respectively) and an increase in Enterococcus and Enterobacteriaceae (P < 0.01 and P < 0.001, respectively) on intestinal mucosa. The severity of liver and gut microbiota alterations induced by I/R was even greater in rats with liver inflammation and steatosis, i.e., MCD-fed animals. LP F19 supplementation significantly reduced the harmful effects of I/R on the liver and on gut microbiota in both groups of rats, although the effect was slightly less in MCD-fed animals. In conclusion, LP-F19 supplementation, by restoring gut microbiota, attenuated I/R-related liver injury, particularly in the absence of steatosis. PMID- 20576922 TI - Molecular species identification of Astrotoma agassizii from planktonic embryos: further evidence for a cryptic species complex. AB - The phrynophiurid brittle star Astrotoma agassizii is abundant in the cold temperate Magellanic region of South America and has a circumpolar Antarctic distribution. Three genetically distinct lineages were recently identified, with one in Antarctica geographically and genetically isolated from both South American lineages (Hunter R, Halanych KM. 2008. Evaluating connectivity in the brooding brittle star Astrotoma agassizii across the Drake Passage in the Southern Ocean. J Hered. 99:137-148.). Despite being an apparent brooding species, A. agassizii displayed a high genetic homogeneity at 2 mitochondrial markers (16s and COII) across a geographical range of more than 500 km along the Antarctic Peninsula. Here, using 16s ribosomal RNA sequences, we match a variety of early developmental stages (fertilized eggs, embryos; n = 12) collected from plankton samples in the Ross Sea to sequences of A. agassizii from the Antarctic Peninsula. The single 16s haplotype reported here is an identical match to one 16s haplotype found for A. agassizii from the Antarctic Peninsula, more than 5000 km away. Based on the regular occurrence of A. agassizii developmental stages in plankton samples, we propose that the Antarctic lineage of this species has a planktonic dispersive stage, with brooding restricted to the South American lineages. A different developmental mode would provide further evidence for cryptic speciation in this brittle star. PMID- 20576923 TI - The Employment Precariousness Scale (EPRES): psychometric properties of a new tool for epidemiological studies among waged and salaried workers. AB - BACKGROUND: Despite the fact that labour market flexibility has resulted in an expansion of precarious employment in industrialised countries, to date there is limited empirical evidence concerning its health consequences. The Employment Precariousness Scale (EPRES) is a newly developed, theory-based, multidimensional questionnaire specifically devised for epidemiological studies among waged and salaried workers. OBJECTIVE: To assess the acceptability, reliability and construct validity of EPRES in a sample of waged and salaried workers in Spain. METHODS: A sample of 6968 temporary and permanent workers from a population-based survey carried out in 2004-2005 was analysed. The survey questionnaire was interviewer administered and included the six EPRES subscales, and measures of the psychosocial work environment (COPSOQ ISTAS21) and perceived general and mental health (SF-36). RESULTS: A high response rate to all EPRES items indicated good acceptability; Cronbach's alpha coefficients, over 0.70 for all subscales and the global score, demonstrated good internal consistency reliability; exploratory factor analysis using principal axis analysis and varimax rotation confirmed the six-subscale structure and the theoretical allocation of all items. Patterns across known groups and correlation coefficients with psychosocial work environment measures and perceived health demonstrated the expected relations, providing evidence of construct validity. CONCLUSIONS: Our results provide evidence in support of the psychometric properties of EPRES, which appears to be a promising tool for the measurement of employment precariousness in public health research. PMID- 20576924 TI - Pesticide safety training and practices in women working in small-scale agriculture in South Africa. AB - OBJECTIVES: Unregulated use of pesticides continues in developing countries in the presence of illiteracy and limited safety training and practices. This paper describes training and safety practices when mixing and spraying pesticides, and acetylcholinesterase levels among women farmers in KwaZulu-Natal, South Africa. METHODS: A cross-sectional study conducted in women working in small-scale agriculture in rural KwaZulu-Natal, South Africa in 2006 assessed pesticide training and safety practices using a questionnaire survey and measured acetylcholinesterase levels in 803 women. Three components of safety behaviour were identified through principle component analysis and described. RESULTS: The mean age of participants was 41.8 years (range 18-82 years) with a mean of 6.9 years (range 1-12 years) of education among school attendees. Among the 803 women included, 366 (45.6%) were the primary sprayers on their farm. Only 16.4% of the sprayers had ever attended a pesticide training course and only 18.0% reported ever reading pesticide labels. Of the women using some form of protective equipment, 56.7% and 54.9% reported doing so when mixing and spraying pesticides, respectively. The mean acetylcholinesterase level corrected for haemoglobin among study participants was 28.9 U/g Hb (95% CI 28.4 to 29.4). CONCLUSION: Women working in small-scale agriculture in rural KwaZulu-Natal with limited access to pesticide training observe few safety practices when mixing and spraying pesticides. PMID- 20576925 TI - A historical mortality study among bus drivers and bus maintenance workers exposed to urban air pollutants in the city of Genoa, Italy. AB - OBJECTIVE: A historical mortality cohort study was conducted in Genoa, Italy among public transport workers ever employed between 1949 and 1980, to estimate overall and cause-specific mortality from January 1970 to December 2005 and to examine associations between exposure to urban air pollutants and overall and cause-specific mortality. METHODS: Causes of death for 9267 males (6510 bus drivers, 2073 maintenance workers and 601 white collar workers) were coded according to ICD-9. Standardised mortality ratios (SMRs) and 95% CIs were computed by applying Italian and regional male death rates to person-years of observation for the entire cohort and following stratification by longest held job title and length of and time since first employment using the Poisson regression model. RESULTS: There were 2916 deaths and 230,009 person-years of observation; 17 subjects were lost to follow-up. SMRs for all causes, diseases of the circulatory, respiratory, digestive and genitourinary systems, and for accidents were lower than expected. SMRs (95% CI) were increased for lung cancer (1.16, 1.05 to 1.28), non-Hodgkin's lymphoma (1.23, 0.85 to 1.78), Hodgkin's lymphoma (2.14, 1.19 to 3.87) and diabetes mellitus (1.16, 1.05 to 1.28). The SMR for leukaemia was 0.77 (0.51 to 1.16). Hodgkin's lymphoma mortality was significantly increased among bus drivers (1.62, 1.37 to 5.04). Lung cancer risk was significantly increased among all workers after 30 years' employment and among maintenance workers. CONCLUSIONS: The study failed to show any increased risk for leukaemias. The increased mortality from Hodgkin's lymphoma and lung cancer may be associated with long-term exposure to urban air pollution. PMID- 20576926 TI - Immunohistochemical analyses of long-term extinction of conditioned fear in adolescent rats. AB - Adolescence is a period of heightened emotional reactivity and vulnerability to poor outcomes (e.g., suicide, anxiety, and depression). Recent human and animal neuroimaging studies suggest that dramatic changes in prefrontal cortical areas during adolescence are involved in these effects. The present study explored the functional implications of prefrontal cortical changes during adolescence by examining conditioned fear extinction in adolescent rats. Experiment 1 showed that preadolescent (i.e., postnatal day [P] 24), adolescent (P35), and adult (P70) rats express identical extinction acquisition following 3 white-noise conditioned stimulus (CS) and shock pairings. When tested the next day, however, adolescent rats showed almost complete failure to maintain extinction of CS elicited freezing compared with P24 and P70 rats. It was observed in experiment 2 that following extinction, P24 and P70 rats express significantly elevated levels of phosphorylated mitogen-activated protein kinase (pMAPK) in the infralimbic cortex (IL) compared with adolescent rats. Interestingly, adolescent rats successfully exhibited long-term extinction if the amount of extinction training was doubled (experiment 3). More extinction training also led to increased phosphorylation of MAPK in the IL in these rats. These findings suggest that adolescents are less efficient in utilizing prefrontal areas, which may lead to an impairment in the maintenance of extinguished behavior. PMID- 20576929 TI - Oncometabolite? IDH1 discoveries raise possibility of new metabolism targets in brain cancers and leukemia. PMID- 20576927 TI - From coarse to fine? Spatial and temporal dynamics of cortical face processing. AB - Primary vision segregates information along 2 main dimensions: orientation and spatial frequency (SF). An important question is how this primary visual information is integrated to support high-level representations. It is generally assumed that the information carried by different SF is combined following a coarse-to-fine sequence. We directly addressed this assumption by investigating how the network of face-preferring cortical regions processes distinct SF over time. Face stimuli were flashed during 75, 150, or 300 ms and masked. They were filtered to preserve low SF (LSF), middle SF (MSF), or high SF (HSF). Most face preferring regions robustly responded to coarse LSF, face information in early stages of visual processing (i.e., until 75 ms of exposure duration). LSF processing decayed as a function of exposure duration (mostly until 150 ms). In contrast, the processing of fine HSF, face information became more robust over time in the bilateral fusiform face regions and in the right occipital face area. The present evidence suggests the coarse-to-fine strategy as a plausible modus operandi in high-level visual cortex. PMID- 20576928 TI - L1 and CHL1 Cooperate in Thalamocortical Axon Targeting. AB - Neural cell adhesion molecule close homolog of L1 (CHL1) is a regulator of topographic targeting of thalamic axons to the somatosensory cortex (S1) but little is known about its cooperation with other L1 class molecules. To investigate this, CHL1(-/-)/L1(-/y) double mutant mice were generated and analyzed for thalamocortical axon topography. Double mutants exhibited a striking posterior shift of axons from motor thalamic nuclei to the visual cortex (V1), which was not observed in single mutants. In wild-type (WT) embryos, L1 and CHL1 were coexpressed in the dorsal thalamus (DT) and on fibers along the thalamocortical projection in the ventral telencephalon and cortex. L1 and CHL1 colocalized on growth cones and neurites of cortical and thalamic neurons in culture. Growth cone collapse assays with WT and mutant neurons demonstrated a requirement for L1 and CHL1 in repellent responses to EphrinA5, a guidance factor for thalamic axons. L1 coimmunoprecipitated with the principal EphrinA5 receptors expressed in the DT (EphA3, EphA4, and EphA7), whereas CHL1 associated selectively with EphA7. These results implicate a novel mechanism in which L1 and CHL1 interact with individual EphA receptors and cooperate to guide subpopulations of thalamic axons to distinct neocortical areas essential for thalamocortical connectivity. PMID- 20576930 TI - One conclusion emerges from Interphone study: controversy will continue. PMID- 20576931 TI - Making breast cancer risk assessment personal. PMID- 20576932 TI - Genetic architecture underlying variation in extent and remodeling of the collateral circulation. AB - RATIONALE: Collaterals are arteriole-to-arteriole anastomoses that connect adjacent arterial trees. They lessen ischemic tissue injury by serving as endogenous bypass vessels when the trunk of 1 tree becomes narrowed by vascular disease. The number and diameter ("extent") of native (preexisting) collaterals, plus their amount of lumen enlargement (growth/remodeling) in occlusive disease, show remarkably wide variation among inbred mouse strains (eg, C57BL/6 and BALB/c), resulting in large differences in tissue injury in models of occlusive disease. Evidence suggests similar large differences exist among healthy humans. OBJECTIVE: To identify candidate loci responsible for genetic-dependent collateral variation. METHODS AND RESULTS: Cerebral collateral number and diameter were determined in 221 C57BL/6xBALB/c F2 progeny, followed by linkage analysis to identify quantitative trait loci (QTL) for collateral number and diameter. Four QTL were obtained for collateral number, including epistasis between 2 loci. A QTL that was identical to the strongest QTL for collateral number on chromosome 7 (logarithm of the odds [LOD]=29, effect size=37%) was also mapped for collateral diameter (LOD=17, effect size=30%). Chromosome substitution strain analysis confirmed this locus. We also obtained a unique QTL on chromosome 11 for collateral remodeling after middle cerebral artery occlusion. Association mapping within the chromosome 7 QTL interval using collateral traits measured for 15 inbred strains delineated 172-kbp (P=0.00002) and 290-kbp (P=0.0004) regions on chromosome 7 containing 2 and 7 candidate genes, respectively. CONCLUSIONS: We conclude that collateral extent and remodeling are unique, highly heritable complex traits, with 1 QTL predominantly affecting native collateral number and diameter. PMID- 20576933 TI - Elastin haploinsufficiency results in progressive aortic valve malformation and latent valve disease in a mouse model. AB - RATIONALE: Elastin is a ubiquitous extracellular matrix protein that is highly organized in heart valves and arteries. Because elastic fiber abnormalities are a central feature of degenerative valve disease, we hypothesized that elastin insufficient mice would manifest viable heart valve disease. OBJECTIVE: To analyze valve structure and function in elastin-insufficient mice (Eln(+/-)) at neonatal, juvenile, adult, and aged adult stages. METHODS AND RESULTS: At birth, histochemical analysis demonstrated normal extracellular matrix organization in contrast to the aorta. However, at juvenile and adult stages, thin elongated valves with extracellular matrix disorganization, including elastin fragment infiltration of the annulus, were observed. The valve phenotype worsened by the aged adult stage with overgrowth and proteoglycan replacement of the valve annulus. The progressive nature of elastin insufficiency was also shown by aortic mechanical testing that demonstrated incrementally abnormal tensile stiffness from juvenile to adult stages. Eln(+/-) mice demonstrated increased valve interstitial cell proliferation at the neonatal stage and varied valve interstitial cell activation at early and late stages. Gene expression profile analysis identified decreased transforming growth factor-beta-mediated fibrogenesis signaling in Eln(+/-) valve tissue. Juvenile Eln(+/-) mice demonstrated normal valve function, but progressive valve disease (predominantly aortic regurgitation) was identified in 17% of adult and 70% of aged adult Eln(+/ ) mice by echocardiography. CONCLUSIONS: These results identify the Eln(+/-) mouse as a model of latent aortic valve disease and establish a role for elastin dysregulation in valve pathogenesis. PMID- 20576934 TI - Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification. AB - RATIONALE: The bone morphogenetic proteins (BMPs), a family of morphogens, have been implicated as mediators of calcification and inflammation in the vascular wall. OBJECTIVE: To investigate the effect of altered expression of matrix Gla protein (MGP), an inhibitor of BMP, on vascular disease. METHODS AND RESULTS: We used MGP transgenic or MGP-deficient mice bred to apolipoprotein E mice, a model of atherosclerosis. MGP overexpression reduced vascular BMP activity, atherosclerotic lesion size, intimal and medial calcification, and inflammation. It also reduced expression of the activin-like kinase receptor 1 and the vascular endothelial growth factor, part of a BMP-activated pathway that regulates angiogenesis and may enhance lesion formation and calcification. Conversely, MGP deficiency increased BMP activity, which may explain the diffuse calcification of vascular medial cells in MGP deficient aortas and the increase in expression of activin-like kinase receptor 1 and vascular endothelial growth factor. Unexpectedly, atherosclerotic lesion formation was decreased in MGP-deficient mice, which may be explained by a dramatic reduction in expression of endothelial adhesion molecules limiting monocyte infiltration of the artery wall. CONCLUSIONS: Our results indicate that BMP signaling is a key regulator of vascular disease, requiring careful control to maintain normal vascular homeostasis. PMID- 20576935 TI - Small molecule disruption of G beta gamma signaling inhibits the progression of heart failure. AB - RATIONALE: Excess signaling through cardiac Gbetagamma subunits is an important component of heart failure (HF) pathophysiology. They recruit elevated levels of cytosolic G protein-coupled receptor kinase (GRK)2 to agonist-stimulated beta adrenergic receptors (beta-ARs) in HF, leading to chronic beta-AR desensitization and downregulation; these events are all hallmarks of HF. Previous data suggested that inhibiting Gbetagamma signaling and its interaction with GRK2 could be of therapeutic value in HF. OBJECTIVE: We sought to investigate small molecule Gbetagamma inhibition in HF. METHODS AND RESULTS: We recently described novel small molecule Gbetagamma inhibitors that selectively block Gbetagamma-binding interactions, including M119 and its highly related analog, gallein. These compounds blocked interaction of Gbetagamma and GRK2 in vitro and in HL60 cells. Here, we show they reduced beta-AR-mediated membrane recruitment of GRK2 in isolated adult mouse cardiomyocytes. Furthermore, M119 enhanced both adenylyl cyclase activity and cardiomyocyte contractility in response to beta-AR agonist. To evaluate their cardiac-specific effects in vivo, we initially used an acute pharmacological HF model (30 mg/kg per day isoproterenol, 7 days). Concurrent daily injections prevented HF and partially normalized cardiac morphology and GRK2 expression in this acute HF model. To investigate possible efficacy in halting progression of preexisting HF, calsequestrin cardiac transgenic mice (CSQ) with extant HF received daily injections for 28 days. The compound alone halted HF progression and partially normalized heart size, morphology, and cardiac expression of HF marker genes (GRK2, atrial natriuretic factor, and beta myosin heavy chain). CONCLUSIONS: These data suggest a promising therapeutic role for small molecule inhibition of pathological Gbetagamma signaling in the treatment of HF. PMID- 20576936 TI - PHLPP-1 negatively regulates Akt activity and survival in the heart. AB - RATIONALE: The recently discovered PHLPP-1 (PH domain leucine-rich repeat protein phosphatase-1) selectively dephosphorylates Akt at Ser473 and terminates Akt signaling in cancer cells. The regulatory role of PHLPP-1 in the heart has not been considered. OBJECTIVE: To test the hypothesis that blockade/inhibition of PHLPP-1 could constitute a novel way to enhance Akt signals and provide cardioprotection. METHODS AND RESULTS: PHLPP-1 is expressed in neonatal rat ventricular myocytes (NRVMs) and in adult mouse ventricular myocytes (AMVMs). PHLPP-1 knockdown by small interfering RNA significantly enhances phosphorylation of Akt (p-Akt) at Ser473, but not at Thr308, in NRVMs stimulated with leukemia inhibitory factor (LIF). The increased phosphorylation is accompanied by greater Akt catalytic activity. PHLPP-1 knockdown enhances LIF-mediated cardioprotection against doxorubicin and also protects cardiomyocytes against H(2)O(2). Direct Akt effects at mitochondria have been implicated in cardioprotection and mitochondria/cytosol fractionation revealed a significant enrichment of PHLPP-1 at mitochondria. The ability of PHLPP-1 knockdown to potentiate LIF-mediated increases in p-Akt at mitochondria and an accompanying increase in mitochondrial hexokinase-II was demonstrated. We generated PHLPP-1 knockout (KO) mice and demonstrate that AMVMs isolated from KO mice show potentiated p-Akt at Ser473 in response to agonists. When isolated perfused hearts are subjected to ischemia/reperfusion, p-Akt in whole-heart homogenates and in the mitochondrial fraction is significantly increased. Additionally in PHLPP-1 KO hearts, the increase in p-Akt elicited by ischemia/reperfusion is potentiated and, concomitantly, infarct size is significantly reduced. CONCLUSIONS: These results implicate PHLPP-1 as an endogenous negative regulator of Akt activity and cell survival in the heart. PMID- 20576939 TI - Interview with Eugene Braunwald by Ruth Williams: escaping death and prolonging lives [part 2]. PMID- 20576937 TI - T-tubule remodeling during transition from hypertrophy to heart failure. AB - RATIONALE: The transverse tubule (T-tubule) system is the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes; T-tubule disorganization and loss are linked to decreased contractility in end stage heart failure (HF). OBJECTIVE: We sought to examine (1) whether pathological T-tubule remodeling occurs early in compensated hypertrophy and, if so, how it evolves during the transition from hypertrophy to HF; and (2) the role of junctophilin-2 in T-tubule remodeling. METHODS AND RESULTS: We investigated T-tubule remodeling in relation to ventricular function during HF progression using state-of-the-art confocal imaging of T-tubules in intact hearts, using a thoracic aortic banding rat HF model. We developed a quantitative T-tubule power (TT(power)) index to represent the integrity of T-tubule structure. We found that discrete local loss and global reorganization of the T-tubule system (leftward shift of TT(power) histogram) started early in compensated hypertrophy in left ventricular (LV) myocytes, before LV dysfunction, as detected by echocardiography. With progression from compensated hypertrophy to early and late HF, T-tubule remodeling spread from the LV to the right ventricle, and TT(power) histograms of both ventricles gradually shifted leftward. The mean LV TT(power) showed a strong correlation with ejection fraction and heart weight to body weight ratio. Over the progression to HF, we observed a gradual reduction in the expression of a junctophilin protein (JP-2) implicated in the formation of T-tubule/sarcoplasmic reticulum junctions. Furthermore, we found that JP-2 knockdown by gene silencing reduced T-tubule structure integrity in cultured adult ventricular myocytes. CONCLUSIONS: T-tubule remodeling in response to thoracic aortic banding stress begins before echocardiographically detectable LV dysfunction and progresses over the development of overt structural heart disease. LV T-tubule remodeling is closely associated with the severity of cardiac hypertrophy and predicts LV function. Thus, T-tubule remodeling may constitute a key mechanism underlying the transition from compensated hypertrophy to HF. PMID- 20576940 TI - Deciphering the signals specifying the proepicardium. PMID- 20576941 TI - Competing oscillators in cardiac pacemaking: historical background. AB - Interaction between a membrane oscillator generated by voltage-dependent ion channels and an intracellular calcium signal oscillator was present in the earliest models (1984 to 1985) using representations of the sarcoplasmic reticulum. Oscillatory release of calcium is inherent in the calcium-induced calcium release process. Those historical results fully support the synthesis proposed in the articles in this review series. The oscillator mechanisms do not primarily compete with each; they entrain each other. However, there is some asymmetry: the membrane oscillator can continue indefinitely in the absence of the calcium oscillator. The reverse seems to be true only in pathological conditions. Studies from tissue-level work and on the development of the heart also provide valuable insights into the integrative action of the cardiac pacemaker. PMID- 20576942 TI - An updated overview on Wnt signaling pathways: a prelude for more. AB - Growth factor signaling is required for cellular differentiation, tissue morphogenesis, and tissue homeostasis. Misregulation of intracellular signal transduction can lead to developmental defects during embryogenesis or particular diseases in the adult. One family of growth factors important for these aspects is given by the Wnt proteins. In particular, Wnts have important functions in stem cell biology, cardiac development and differentiation, angiogenesis, cardiac hypertrophy, cardiac failure, and aging. Knowledge of growth factor signaling during differentiation will allow for improvement of targeted differentiation of embryonic or adult stem cells toward functional cardiomyocytes or for understanding the basis of diseases. Our major aim here is to provide a state of the art review summarizing our present knowledge of the intracellular Wnt mediated signaling network. In particular, we provide evidence that the subdivision into canonical and noncanonical Wnt signaling pathways solely based on the identity of Wnt ligands or Frizzled receptors is not appropriate anymore. We thereby deliver a solid base for further upcoming articles of a review series focusing on the role of Wnt proteins on different aspects of cardiovascular development and dysfunction. PMID- 20576944 TI - Time-course analysis on the differentiation of bone marrow-derived progenitor cells into smooth muscle cells during neointima formation. AB - OBJECTIVE: Bone marrow-derived progenitor cells have been implicated to contribute to neointima formation, but the time course and extent of their accumulation and differentiation into vascular cells and, most importantly, the long-term contribution of bone marrow-derived progenitor cells to the vascular lesion remain undefined. METHODS AND RESULTS: Wire-induced injury of the femoral artery was performed on chimeric C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein, and vessels were harvested at 3 days, 1, 2, 3, 4, 6, and 16 weeks after dilatation (n=8 animals per time point). Using high-resolution microscopy, we unexpectedly found that the expression of smooth muscle cell or endothelial cell markers in enhanced green fluorescence protein positive cells was a very rare event. Indeed, most of the enhanced green fluorescence protein positive cells that accumulated during the acute inflammatory response were identified as monocytes/macrophages, and their number declined at later time points. In contrast, a substantial fraction of highly proliferative stem cell antigen-1 and CD34(+) but enhanced green fluorescence protein negative and thus locally derived cells were detected in the adventitia. CONCLUSIONS: These data provide evidence that the differentiation of bone marrow-derived progenitor cells into smooth muscle cell or endothelial cell lineages seems to be an exceedingly rare event. Moreover, the contribution of bone marrow-derived cells to the cellular compartment of the neointima is limited to a transient period of the inflammatory response. PMID- 20576943 TI - Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway. AB - OBJECTIVE: Factors released by perivascular adipose tissue (PVAT) disrupt coronary endothelial function via phosphorylation of endothelial NO synthase by protein kinase C (PKC)-beta. However, our understanding of how PVAT potentially contributes to coronary disease as a complication of obesity/metabolic syndrome (MetS) remains limited. The current study investigated whether PVAT-derived leptin impairs coronary vascular function via PKC-beta in MetS. METHODS AND RESULTS: Coronary arteries with and without PVAT were collected from lean or MetS Ossabaw miniature swine for isometric tension studies. Endothelial-dependent vasodilation to bradykinin was significantly reduced in MetS. PVAT did not affect bradykinin-mediated dilation in arteries from lean swine but significantly exacerbated endothelial dysfunction in arteries from MetS swine. PVAT-induced impairment was reversed by inhibition of either PKC-beta with ruboxistaurin (Eli Lilly and Company, Indianapolis, Ind) or leptin receptor signaling with a recombinant, pegylated leptin antagonist. Western blot and immunohistochemical analyses demonstrated increased PVAT-derived leptin and coronary leptin receptor density with MetS. Coronary PKC-beta activity was increased in both MetS arteries exposed to PVAT and lean arteries exposed to leptin. Finally, leptin-induced endothelial dysfunction was reversed by ruboxistaurin. CONCLUSIONS: Increases in epicardial PVAT leptin exacerbate coronary endothelial dysfunction in MetS via a PKC-beta-dependent pathway. These findings implicate PVAT-derived leptin as a potential contributor to coronary atherogenesis in MetS. PMID- 20576945 TI - Pioglitazone versus glimepiride on coronary artery calcium progression in patients with type 2 diabetes mellitus: a secondary end point of the CHICAGO study. AB - OBJECTIVE: To compare coronary artery calcium (CAC) progression between 2 treatment groups, pioglitazone versus glimepiride. METHODS AND RESULTS: The CHICAGO (Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone) study demonstrated that pioglitazone significantly decreased carotid intima-media thickness progression compared with glimepiride in patients with type 2 diabetes mellitus. The CAC level was determined at baseline and at the end of 72 weeks of treatment in the pioglitazone (n=146) and glimepiride (n=153) treatment groups using electron beam computed tomography. There was no difference in CAC progression between the treatment groups. By using backward and forward selection models, age, race/ethnicity, and baseline apolipoprotein B level predicted CAC progression. There was no relationship between carotid intima-media thickness and CAC progression during the study. CONCLUSIONS: There was no difference in CAC progression in patients with type 2 diabetes mellitus treated with pioglitazone or glimepiride. Age, race/ethnicity, and baseline apolipoprotein B level predicted CAC progression in patients with type 2 diabetes mellitus. PMID- 20576946 TI - Perception of weight-bearing distribution during sit-to-stand tasks in hemiparetic and healthy individuals. AB - BACKGROUND AND PURPOSE: It is unknown whether hemiparetic individuals are aware of their weight-bearing asymmetry during sit-to-stand tasks. This study compared the error between hemiparetic and healthy individuals' perception of weight bearing and their actual weight-bearing distribution during the sit-to-stand task and analyzed the association between the knee extensor muscle strength and the weight-bearing distribution and perception. METHODS: Nineteen unilateral hemiparetic subjects and 15 healthy individuals participated in the study. They performed the sit-to-stand transfer on force platforms under different foot placements (spontaneous and symmetrical) and had to rate their perceived weight bearing distribution at the lower limbs on a visual analog scale. The strength of the knee extensors was assessed with a Biodex dynamometer. RESULTS: The hemiparetic individuals presented greater weight-bearing asymmetry and errors of perception than the healthy individuals. Although no significant association was found between strength and weight-bearing perception, moderate associations were found between strength and weight-bearing distribution for both the spontaneous (r=0.75, P<0.01) and symmetrical (r=0.71, P<0.01) foot position conditions. CONCLUSIONS: This study revealed that individuals with hemiparesis after a stroke do not perceive themselves as asymmetrical when executing the sit-to-stand transfer and that the knee extensor strength is a factor linked to their weight bearing asymmetry, not to their perception. PMID- 20576947 TI - Preswing knee flexion assistance is coupled with hip abduction in people with stiff-knee gait after stroke. AB - BACKGROUND AND PURPOSE: Stiff-knee gait is defined as reduced knee flexion during the swing phase. It is accompanied by frontal plane compensatory movements (eg, circumduction and hip hiking) typically thought to result from reduced toe clearance. As such, we examined if knee flexion assistance before foot-off would reduce exaggerated frontal plane movements in people with stiff-knee gait after stroke. METHODS: We used a robotic knee orthosis to assist knee flexion torque during the preswing phase in 9 chronic stroke subjects with stiff-knee gait on a treadmill and compared peak knee flexion, hip abduction, and pelvic obliquity angles with 5 nondisabled control subjects. RESULTS: Maximum knee flexion angle significantly increased in both groups, but instead of reducing gait compensations, hip abduction significantly increased during assistance in stroke subjects by 2.5 degrees , whereas no change was observed in nondisabled control subjects. No change in pelvic obliquity was observed in either group. CONCLUSIONS: Hip abduction increased when stroke subjects received assistive knee flexion torque at foot-off. These findings are in direct contrast to the traditional belief that pelvic obliquity combined with hip abduction is a compensatory mechanism to facilitate foot clearance during swing. Because no evidence suggested a voluntary mechanism for this behavior, we argue that these results were most likely a reflection of an altered motor template occurring after stroke. PMID- 20576948 TI - Outcomes of thrombolysis for acute ischemic stroke in octogenarians versus nonagenarians. AB - BACKGROUND AND PURPOSE: Little is reported on the outcomes of nonagenarians who are treated with intravenous tissue plasminogen activator for acute ischemic stroke. It is uncertain whether nonagenarians have higher mortality and worse functional outcomes than octogenarians. METHODS: All patients who were >or=80 years of age were extracted from the Canadian Activase for Stroke Effectiveness Study national registry, a 60-center Canadian acute ischemic stroke treatment network. Patients were divided into 2 groups: those who were 80 to 89 years of age (octogenarians) and those who were 90 to 99 years of age (nonagenarians), and compared by baseline clinical, demographic, treatment, and outcome-related measures. RESULTS: Twenty-eight nonagenarians and 242 octogenarians were treated with intravenous tissue plasminogen activator for acute ischemic stroke over the 2.5-year observation period. Nonagenarians and octogenarians did not differ on any of the baseline clinical or demographic variables. Both groups were predominantly female (77% nonagenarians and 61% octogenarians), hypertensive (54% and 60%), and predominantly had severe strokes (National Institutes of Health Stroke Scale score >15; 58% and 52%). The rate of symptomatic intracerebral hemorrhage (7% nonagenarians versus 4% octogenarians; P=0.359), 90-day mortality (52% versus 33%; P=0.087), and 30-day favorable functional outcomes ([modified Rankin score or=3 of 10 grades between baseline and follow-up. RESULTS: After adjusting for age, gender, and cardiovascular risk factors, retinopathy and arteriovenous nicking at baseline were associated with 10-year ventricular enlargement (OR and 95% CI: 2.03, 1.20 to 4.42 for retinopathy and 2.19, 1.23 to 3.90 for arteriovenous nicking). Retinal signs were not associated with 10-year sulcal widening. CONCLUSIONS: Retinopathy and arteriovenous nicking are predictive of long-term risk of ventricular enlargement, but not of sulcal widening, independent of cardiovascular risk factors. These data support a microvascular etiology for subcortical but not cortical cerebral atrophy. PMID- 20576952 TI - Minor allele C of chromosome 1p32 single nucleotide polymorphism rs11206510 confers risk of ischemic stroke in the Chinese Han population. AB - BACKGROUND AND PURPOSE: Genome-wide association studies found that the common allele T of single nucleotide polymorphism rs11206510 on chromosome 1p32 was associated with increased low-density lipoprotein-cholesterol levels (LDL-C) and with risk of coronary artery disease (CAD) in white populations. The goals of this study are to determine whether rs11206510 is associated with LDL-C and CAD in a different ethnic population, namely a Chinese cohort, and to investigate whether rs11206510 is associated with ischemic stroke. METHODS: The association of rs11206510 with LDL-C was analyzed in 1415 Chinese Han subjects. The CAD study utilized a GeneID cohort with 1543 CAD patients and 1240 controls. For stroke studies, 2 independent cohorts were used and included the GeneID North cohort, with 1205 cases and 1205 controls, and the GeneID Central cohort, with 692 cases and 882 controls. RESULTS: Different from white populations, the minor allele C of rs11206510 was associated with increased LDL-C levels in the Chinese Han population (adjusted P=0.002) and conferred risk of early-onset CAD (380 cases vs 1240 controls; adjusted P=0.002, odds ratio, 1.89), but not with overall CAD (adjusted P=0.82). The allelic association with ischemic stroke was highly significant in 2 independent cohorts, with adjusted P=1.13x10(-5) (odds ratio,1.71) in the GeneID North cohort and adjusted P=9.32x10(-5) (odds ratio, 1.70) in the GeneID Central cohort. Genotypic association was also significant for both early-onset CAD and ischemic stroke. CONCLUSIONS: Our results indicate that single nucleotide polymorphism rs11206510 is associated with LDL-C levels and early-onset CAD in the Chinese Han population. For the first time to our knowledge, this study also demonstrates that rs11206510 confers a significant risk of ischemic stroke. PMID- 20576953 TI - MicroRNAs induced during ischemic preconditioning. AB - BACKGROUND AND PURPOSE: MicroRNAs (miRNA) are single-stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Although miRNAs control a number of conditions and diseases, few neuroprotective miRNAs have been described. In this study, we investigated neuroprotective miRNAs induced early in ischemic preconditioning. METHODS: Ischemic preconditioning or focal cerebral ischemia was induced in mice by transient occlusion of the middle cerebral artery for 15 or 120 minutes. We prepared RNA samples from the ischemic cortex at 3 or 24 hours after the onset of ischemia. Selective miRNAs then were synthesized and transfected into Neuro-2a cells before oxygen-glucose deprivation. RESULTS: We detected a total of 360 miRNAs. Two miRNA families, miR-200 and miR-182, were selectively upregulated at 3 hours after ischemic preconditioning. Transfections of some of these were neuroprotective in in vitro ischemia. Among them, miR-200b, miR-200c, and miR-429 targeted prolyl hydroxylase 2 and had the best neuroprotective effect. CONCLUSIONS: Two miRNA families, miR-200 and miR-182, were upregulated early after ischemic preconditioning and the miR-200 family was neuroprotective mainly by downregulating prolyl hydroxylase 2 levels. These miRNAs may be useful in future research and therapeutic applications. PMID- 20576954 TI - Impaired cerebrovascular reactivity with steal phenomenon is associated with increased diffusion in white matter of patients with Moyamoya disease. AB - BACKGROUND AND PURPOSE: Reduced cerebrovascular reactivity (CVR) with steal phenomenon is an independent predictor for stroke and may indicate tissue exposed to episodic low-grade ischemia. The apparent diffusion coefficient (ADC) calculated using diffusion-weighted MRI is effective in characterizing focal brain ischemia and subtle structural changes in normal-appearing white matter (WM). We hypothesized that regions of steal phenomenon are associated with increased ADC in normal-appearing WM of patients with Moyamoya disease. METHODS: Twenty-two patients with unilateral CVR impairment secondary to Moyamoya disease and 12 healthy control subjects underwent diffusion-weighted MRI and functional MRI mapping of the cerebrovascular response to hypercapnia. Parametric maps of ADC and CVR were calculated, coregistered, and segmented using automated image processing methods. ADC of normal-appearing WM was compared between hemispheres, and between WM with negative CVR (ie, steal phenomenon) and WM with positive CVR. RESULTS: In patients, ADC of normal-appearing WM was elevated in the hemisphere ipsilateral to the CVR impairment compared with the contralateral hemisphere (P<0.005) and in WM with negative CVR compared with WM with positive CVR (P<0.001). WM in regions of steal phenomenon within the affected hemisphere had higher ADC than homologous contralateral WM (P<0.005). In control subjects, negative CVR in WM was not associated with elevated ADC. CONCLUSIONS: Regions of steal phenomenon are spatially correlated with elevated ADC in normal-appearing WM of patients with Moyamoya disease. This structural abnormality may reflect low grade ischemic injury after exhaustion of the cerebrovascular reserve capacity. PMID- 20576955 TI - Characterization of carotid plaque hemorrhage: a CT angiography and MR intraplaque hemorrhage study. AB - BACKGROUND AND PURPOSE: The main objective of this study was to evaluate CT angiographic (CTA) features that are able to predict the presence of intraplaque hemorrhage (IPH) as defined by MR-IPH. METHODS: One hundred sixty-seven consecutive patients (mean age 69 years, SD 12.8; 58 females) underwent both MR IPH and CTA within 3 weeks. MR-IPH, the gold standard, was performed at 1.5 T using a neurovascular phased-array coil as a coronal T1-weighted 3-dimensional fat-suppressed acquisition. CTA was performed using a 4-slice or a 64-slice CT machine and evaluated, blinded to MR-IPH findings, for carotid stenosis, plaque density, and plaque ulceration. Plaque density was defined as the mean attenuation of plaque at the site of maximum stenosis and 2 sections above and below. Plaque ulceration was defined as outpouching of contrast into the plaque at least 2 mm deep on any single plane. RESULTS: Prevalence of IPH increased at higher degrees of carotid stenosis. Mean CT plaque density was higher for plaques with MRI-defined IPH (47 Hounsfield units) compared with without IPH (43 Hounsfield units; P=0.02). However, significant overlap between distributions of plaque densities limited the value of mean plaque density for prediction of IPH. CTA plaque ulceration had high sensitivity (80.0% to 91.4%), specificity (93.0% to 92.3%), positive predictive value (72.0% to 71.8%), and negative predictive value (95.0% to 97.9%) for prediction of IPH. Interobserver agreement for presence/absence of CTA plaque ulceration was excellent (kappa=0.80). CONCLUSIONS: CTA plaque ulceration, but not mean CTA plaque density, was useful for prediction of IPH as defined by the MR-IPH technique. PMID- 20576956 TI - Stem cell-derived neurons grafted in the striatum are expelled out of the brain after chronic cortical stroke. AB - BACKGROUND AND PURPOSE: In humans and rodents, cortical stroke can lead to cortex atrophy in long-term survivors. In the rodent, fetal brain neural precursors or stem cell-derived neurons grafted in the stroke-lesioned brain integrate successfully and reduce infarct in the short term. We have examined the fate, in the long term, of mouse embryonic stem cell-derived neural precursors grafted after permanent middle cerebral artery occlusion in mice. METHODS: Green fluorescent protein-labeled neural precursors were grafted in the striatum of control and lesioned mice and their fate examined 9 months later. RESULTS: In control mice, the neuronal progeny of mouse embryonic stem cells innervated distant brain structures, in a way remarkably similar between animals, displayed a laterality preference and remained polysialated neural cell adhesion molecule immunoreactive. In lesioned mice, grafted cells were expelled out of the brain. CONCLUSIONS: Stroke-related brain atrophy and reshaping were not prevented by cell grafting and, eventually, led to the expulsion of the graft. PMID- 20576957 TI - Evidence-based management of neuromuscular block. PMID- 20576958 TI - Monitoring and pharmacologic reversal of a nondepolarizing neuromuscular blockade should be routine. PMID- 20576959 TI - Neuromuscular monitoring: what evidence do we need to be convinced? PMID- 20576960 TI - Managing neuromuscular block: where are the guidelines? PMID- 20576961 TI - Neuromuscular block: views from the Western pacific. PMID- 20576962 TI - Out of a cell into this darkened space. PMID- 20576963 TI - The adverse effects of volatile anesthetics: a conundrum. PMID- 20576964 TI - Robots with a social memory. PMID- 20576965 TI - PRO: accumulating evidence for an outrageous claim. PMID- 20576967 TI - Inadequate lung isolation in association with asymmetric inflation of an Arndt bronchial blocker. PMID- 20576966 TI - CON: anesthesia versus analgesia: assessing the analgesic effects of anesthetic drugs. PMID- 20576969 TI - New sensors should improve Masimo SpMet error found by Feiner et al. PMID- 20576972 TI - Importance of serum [Na+] and [Cl-] difference in acid-base status classification. PMID- 20576973 TI - Correction of attribution. PMID- 20576975 TI - Reducing the risks associated with videolaryngoscopy. PMID- 20576976 TI - Fractured small gauge needle during attempted combined spinal-epidural anesthesia for cesarean delivery. PMID- 20576979 TI - Creative solutions to psychiatry's increasing reliance on residents as teachers. PMID- 20576981 TI - The Education Chief Resident in Medical Student Education: indicators of success. AB - OBJECTIVE: Although residents are actively involved in teaching medical students, some students do not feel that they get adequate teaching from residents. The position of Education Chief Resident in Medical Student Education was developed to enhance the educational experience for the students, cultivate the academic skills of the education chief, and liaise between students and residents. METHODS: The education chiefs spend 10-12 hours a week teaching medical students, assisting primarily with clerkships. To determine student satisfaction with the position of education chief, 85 students were surveyed in the 2007-2008 academic year. The education chiefs were also surveyed regarding their perceptions of how this position benefited their academic development. RESULTS: Seventy-six medical students completed the survey for a response rate of 89%. Students rated highly having education chiefs as part of the psychiatry clerkship. The education chief residents felt that their teaching skills and educational development were enhanced and that the position helped prepare them for careers in academic psychiatry. CONCLUSION: The position of education chief was viewed as valuable to the medical student experience in the psychiatry clerkship, and the education chiefs felt that the position enhanced their professional and educational development. PMID- 20576980 TI - Therapy 101: a psychotherapy curriculum for medical students. AB - OBJECTIVE: This pilot project, designed and taught by a resident, created a curriculum to introduce medical students to the practice of psychotherapy. Medical students who are knowledgeable about psychotherapy can become physicians who are able to refer patients to psychotherapeutic treatments. A search of the literature did not identify a curriculum that introduced psychotherapy, its applications, and evidence for its use. METHODS: The authors worked closely with a faculty mentor to create a course that fulfilled a perceived need for more psychotherapy teaching of medical students. "Therapy 101: An Introduction to Psychotherapy" is a 6-hour curriculum that employs creative teaching techniques such as video clips from TV shows, role play, and recordings of therapy sessions. The series was evaluated using a multiple-choice pre/postcourse test with questions on psychotherapy, written feedback, and perceived knowledge of psychotherapy. RESULTS: The scores from the pre/postcourse test measuring the students' knowledge of psychotherapy did not change significantly. However, students' self-rating of knowledge greatly increased after the series. Written feedback showed substantial enthusiasm for the course. CONCLUSION: Students can benefit from a short and engaging curriculum on psychotherapy. "Therapy 101" was very well accepted by students and has been integrated into the curriculum for students in the mental health pathway. Medical students may benefit from more exposure to psychotherapy as taught by a resident. PMID- 20576982 TI - The feasibility and effectiveness of a pilot resident-organized and -led knowledge base review. AB - OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME) requires a sufficient medical knowledge base as one of the six core competencies in residency training. The authors judged that an annual "short-course" review of medical knowledge would be a useful adjunct to standard seminar and rotation teaching, and that a resident-designed course might more closely meet resident identified needs and learning styles. METHODS: Our residency training program designed a formal summer short-course, called the Knowledge Base Review (KBR), with the hypothesis that the course would improve general knowledge as measured by the Psychiatry Resident-in-Training Examination (PRITE) and with the objective that this program would enrich the residents' general knowledge base in psychiatry and neurology. The authors designed the KBR as a weekly curriculum composed of nine 2-hour sessions, each equally didactic- and active learning based. The first hour spotlighted one of the subscales of the PRITE. The second hour used a question and answer test in which four teams of residents competed to answer in game show style. Qualitative and quantitative assessment of the KBR was conducted. RESULTS: Attendance among the PGY-2, -3, and -4 classes was 82%, 73%, and 94%, respectively. Participating residents completed a survey midway through the KBR. Ninety-five percent responded that the course was meeting their own expectations "all" and "most of the time," 100% responded that the didactic component was useful, and 94% felt that the game show component was useful. Among 23 residents who took the PRITE in the year prior to and the year after the KBR, there was a 2.6% increase in PRITE global psychiatry scores (p=0.15) in contrast to a 9.0% decline in global neurology scores (p=0.001), which was not addressed in the KBR. CONCLUSION: The broad participation and acceptability of the course and the performance difference in PRITE scores between the psychiatry topics, the majority of which were reviewed, and neurology, which was not reviewed, suggest the potential for such a resident-organized and -led intervention to impact acquisition of medical knowledge through an enjoyable and effective approach. PMID- 20576983 TI - An assigned teaching resident rotation. AB - OBJECTIVE: The authors' adult psychiatry residency training program identified several educational needs for residents at their institution. Junior residents needed enhanced learning of clinical interviewing skills and learning connected to the inpatient psychiatry ward rotations, and senior residents needed opportunities to prepare for the specialty board exam and to develop teaching skills in preparation for attending positions. Changing the residency program structure and implementing a Teaching Resident rotation addressed these needs simultaneously. METHODS: The authors describe the responsibilities of the teaching resident, the role of the teaching resident in the program, and instruction in educational methods. Residents shared their perceptions of the new teaching resident rotation in an anonymous survey. RESULTS: PGY-1, PGY-2, and the PGY-4 residents found the teaching resident rotation helpful in many areas of their learning. CONCLUSION: Service requirements were not compromised and highly valuable educational objectives were achieved for both the PGY-4 teaching residents and the PGY-1 and PGY-2 residents whom they taught. An intensive teaching rotation for senior residents who teach junior residents and medical students is an effective way to deal with systemic changes in psychiatric education. PMID- 20576984 TI - Clinician-educator tracks for residents: three pilot programs. AB - OBJECTIVE: Over the past 30 years, clinician-educators have become a prominent component of medical school faculties, yet few of these individuals received formal training for this role and their professional development lags behind other faculty. This article reviews three residency tracks designed to build skills in teaching, curriculum development and assessment, education research, and career development to meet this need. METHODS: The residency clinician educator tracks at University of Michigan, Baylor College of Medicine, and University of California Davis are described in detail, with particular attention to their common elements, unique features, resource needs, and graduate outcomes. RESULTS: Common elements in the tracks are faculty mentorship, formal didactics, teaching opportunities, and an expectation of scholarly productivity. Essential resources include motivated faculty, departmental support, and a modest budget. Favorable outcomes include a high percentage of graduates in clinical faculty positions, teaching programs created by the residents, positive effects on recruitment, and enhancement of faculty identity as clinician educators. CONCLUSION: Clinician-educator tracks in residency present a viable means to address the training needs of clinical track faculty. The programs described in this article provide a model to assist other departments in developing similar programs. PMID- 20576985 TI - Teaching to Teach in Toronto. AB - OBJECTIVE: The training objectives for postgraduate education in the United States and Canada both state that teaching skills should be formally developed during training. This article reviews the development of the Teaching-to-Teach program at the University of Toronto Department of Psychiatry, the current curriculum, evaluation, and future directions of the program. The authors highlight some of the challenges encountered and discuss ideas for implementation of similar programs in diverse training settings. METHODS: A Teaching-to-Teach curriculum was developed with separate tracks for junior and senior residents. Topics covered include one-to-one teaching, the one-minute clinical preceptor model, challenging teaching scenarios, and providing effective feedback. RESULTS: In 2007, 100% of residents who responded to an evaluation questionnaire agreed or strongly agreed that the topics covered were relevant, and in 2008, 92% of respondents agreed that topics were relevant. In 2007, all respondents agreed or strongly agreed that they felt more prepared to teach. In 2008, 85% of respondents felt more prepared to teach. In 2007, all respondents felt that the amount of teaching was good or too little, but in 2008, 46% of respondents felt there was too much teaching. CONCLUSION: The large size of the University of Toronto psychiatry program may make this curriculum difficult to generalize to smaller training sites. The use of online modules, collaboration between programs, or individual teaching electives may be other ways of implementing a teaching to teach program. Overall, our curriculum was well-received by trainees and they felt better prepared to take on the role of teacher after participating. PMID- 20576986 TI - A longitudinal "teaching-to-teach" curriculum for psychiatric residents. AB - OBJECTIVE: Psychiatric residents' self-reported confidence levels related to teaching medical students were assessed before and after a five-part teaching seminar series. METHODS: Five 1-hour seminars on teaching medical students in the psychiatry clerkship were presented to second postgraduate year (PGY-2) residents. Topics included how to teach psychiatric interviewing, the mental status exam, case formulation, giving feedback, and evaluating student work. Residents were surveyed before and after the seminar series to assess their levels of confidence to teach specific skills. RESULTS: A greater percentage of PGY-2 residents rated themselves as "very confident" in teaching and providing feedback to medical students after the seminar series than before the series. The greatest increases were seen in confidence to teach interviewing skills, the mental status exam, psychiatric formulation, and to evaluate student work. CONCLUSION: A specific how-to-teach curriculum helped improve PGY-2 resident confidence for teaching medical students during the psychiatry clerkship. PMID- 20576988 TI - Experiential anamnesis and group consensus: an innovative method to teach residents to teach. AB - OBJECTIVE: Using a novel method, residents generated examples and principles of good medical teaching from their experiences of being taught as medical students. This article describes and evaluates this method of teaching preparation, gives the main teaching principles the residents derived, and provides representative examples of their experiences which illustrate each principle. METHODS: In this 2 hour session, postgraduate year two (PGY-2) psychiatric residents shared their most notable experiences of being taught as medical students with their cohort and a faculty facilitator and, from these experiences, articulated principles of medical teaching for their immediate use as psychiatric clerkship teachers. The residents responded to a survey questionnaire to gauge the value of the method. RESULTS: In 2009, 11 PGY-2 residents recollected 18 experiences of peak or poor teaching and derived five major principles of teaching from them in an affectively intense and cognitively engaging group exercise. The survey results indicated that the session caused residents to feel better prepared for medical student teaching. CONCLUSION: This method of peer group processing mobilized residents' memories of being taught and organized them into practical principles of good teaching. PMID- 20576990 TI - Growing Teachers: using electives to teach senior residents how to teach. AB - OBJECTIVE: Many physicians teach but few are taught how to teach, particularly through pedagogical interventions. The authors describe a method for teaching curriculum development and classroom skills to psychiatric residents using an elective in the fourth postgraduate year. METHODS: An elective in pedagogy provided a framework for the planning, teaching, and evaluation phases of developing a new course. RESULTS: The elective resulted in four new, well received courses and encouraged two participants to pursue careers in academic psychiatry. CONCLUSION: The elective helped residents achieve essential teaching skills, foster mentoring relationships with senior teaching faculty, and develop as future junior faculty members. PMID- 20576991 TI - Trainees as teachers in team-based learning. AB - OBJECTIVE: Team-based learning is an active learning modality that is gaining popularity in medical education. The authors studied the effect of using trainees as facilitators of team-based learning sessions. METHODS: Team-based learning modules were developed and implemented by faculty members and trainees for the third-year medical student clerkship in psychiatry in the 2007-2008 academic year. Evaluation forms were used to elicit student opinions about the team-based learning sessions. Scores for trainee and faculty facilitators were compared using Student's t tests. RESULTS: Overall scores were positive, reflecting acceptability of this form of instruction. Eight of nine comparisons showed no difference in students' ratings of faculty versus trainee facilitators. The other comparison showed a modest preference for faculty facilitators. CONCLUSION: Team based learning modules can be led as effectively by trainees as by faculty members to teach medical students in the classroom setting. PMID- 20576992 TI - Toolbox for evaluating residents as teachers. AB - OBJECTIVE: The authors review existing assessment tools related to evaluating residents' teaching skills and teaching effectiveness. METHODS: PubMed and PsycInfo databases were searched using combinations of keywords including "residents," "residents as teachers," "teaching skills," and "assessments" or "rating scales." RESULTS: Eleven evaluation tools that utilized self-reports, learner evaluations, or observed structured teaching evaluations were found. These varied in length from one to 58 items, most of which were both valid and reliable. Additional evaluation tools were found that utilized direct audio- or videotaped recordings of teaching. CONCLUSION: This toolbox should facilitate program directors and others in assessing residents' teaching skills and should promote rigorously conducted research on residents as teachers. PMID- 20576993 TI - The Chief Resident for Psychotherapy: a novel teaching role for senior residents. PMID- 20576994 TI - Psychiatric residents as teachers: development and evaluation of a teaching manual. AB - OBJECTIVE: Psychiatric residents spend much time as teachers and mentors to medical students. Recently, the Canadian Medical Education Directions for Specialists (CanMEDS) roles identified the importance of this role as a scholar. Residents are now expected to develop skills to fulfill this role, one of which involves the ability to teach. However, lack of tools to facilitate the development of resident teaching skills poses a significant problem. METHODS: This article describes the development and evaluation of a resident teaching manual, written by psychiatric residents for use by fellow residents, in their teaching endeavors with medical students at the University of Alberta. RESULTS: Residents appreciated using this manual to enhance their skills in teaching medical students. CONCLUSION: The development of, and the preliminary survey of this psychiatric resident teaching manual, is encouraging in furthering the development of future psychiatrist teachers. PMID- 20576995 TI - Writing multiple-choice questions. PMID- 20576996 TI - One-Minute Preceptor model: brief description and application in psychiatric education. PMID- 20576997 TI - Performance examinations in psychiatry: drawbacks of the long case. PMID- 20576998 TI - Patient empowerment and multimodal hand hygiene promotion: a win-win strategy. AB - Patient empowerment is a new concept in health care that has now been extended to the domain of patient safety. Within the framework of the development of the new World Health Organization (WHO) Guidelines on Hand Hygiene in Health Care, the authors conducted a review of the literature from 1997 to 2008 to identify the evidence supporting programs aimed at encouraging patients to take an active role in their care. Patient empowerment is an integral part of the WHO hand hygiene multimodal strategy. Hand hygiene promotion strategies that have demonstrated evidence of successfully empowering patients include one or all of the following components: educational tools, motivation and reminder tools, and role modeling. What is important is that programs and models to empower patients must be developed with an inbuilt evaluation component that includes both qualitative and quantitative measures to determine not only what works but under what conditions and within which organizational context. PMID- 20576999 TI - Emergency endoscopy cover: cost and benefits? PMID- 20577001 TI - A core questionnaire for the assessment of patient satisfaction in academic hospitals in The Netherlands: development and first results in a nationwide study. AB - BACKGROUND: Patient satisfaction is one of the relevant indicators of quality of care; however, measuring patient satisfaction had been criticised. A major criticism is that many instruments are not reliable and/or valid. The instruments should have enough discriminative power for benchmarking of the results. OBJECTIVE: To develop a "core questionnaire for the assessment of patient satisfaction in academic hospitals" (COPS) that is reliable and appropriate for benchmarking patient satisfaction results. RESEARCH DESIGN: The development of COPS, the testing of its psychometric quality and its use in eight Dutch academic hospitals in three national comparative studies in 2003, 2005 and 2007 are described in this study. Results were reported only if they were significant (p<0.05) and relevant (also Cohen d>0.2). RESULTS: The questionnaire was returned in 2003 by 40,678 patients (77,450 sent, 53%) and by 40,248 patients (75,423 sent, 53%) in 2005. In 2007, the questionnaire was returned by 45,834 patients (87,137, 53%). The six dimensions have good Cronbach alpha's, varying from 0.79 to 0.88.The results of every item were reported to the individual hospital. A benchmark overview showed the overall comparison of all specialties of the eight hospitals for the clinic and outpatient departments. The 2007 measurement showed relevant differences in satisfaction on two dimensions in the clinical setting. CONCLUSIONS: COPS is shown to be a feasible and reliable instrument to measure the satisfaction of patients in Dutch academic hospitals. It allows comparison of hospitals and gives benchmark information on a hospital as well as data on specialty levels and previous measurements, including best practices. PMID- 20577002 TI - SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations. AB - BACKGROUND: Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS). METHODS: The relative contributions of the different mutations to ALS were estimated by systematically screening a cohort of 162 families enrolled in France and 500 controls (1000 chromosomes) using molecular analysis techniques and performing phenotype genotype correlations. RESULTS: 31 pathogenic missense mutations were found in 36 patients (20 SOD1, 1 ANG, 1 VAPB, 7 TARDBP and 7 FUS). Surprisingly two FUS mutation carriers also harboured ANG variants. One family of Japanese origin with the P56S VAPB mutation was identified. Seven novel mutations (three in SOD1, two in TARDBP, two in FUS) were found. None of them was detected in controls. Segregation of detected mutations with the disease was confirmed in 11 families including five pedigrees carrying the novel mutations. Clinical comparison of SOD1, TARDBP, FUS and other familial ALS patients (with no mutation in the screened genes) revealed differences in site of onset (predominantly lower limbs for SOD1 and upper limbs for TARDBP mutations), age of onset (younger with FUS mutations), and in lifespan (shorter for FUS carriers). One third of SOD1 patients survived more than 7 years: these patients had earlier disease onset than those presenting with a more typical course. Differences were also observed among FUS mutations, with the R521H FUS mutation being associated with longer disease duration. CONCLUSIONS: This study identifies new genetic associations with ALS and provides phenotype-genotype correlations with both previously reported and novel mutations. PMID- 20577000 TI - Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy. AB - BACKGROUND: There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). AIM: To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. METHODS: Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. RESULTS: 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with >=2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. CONCLUSION: Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression. PMID- 20577003 TI - Identification of clinically significant, submicroscopic chromosome alterations and UPD in fetuses with ultrasound anomalies using genome-wide 250k SNP array analysis. AB - BACKGROUND: The implementation of microarray analysis in prenatal diagnostics is a topic of discussion, as rare copy number variants with unknown/uncertain clinical consequences are likely to be found. The application of targeted microarrays limits such findings, but the potential disadvantage is that relevant, so far unknown, aberrations might be overlooked. Therefore, we explore the possibilities for the prenatal application of the genome-wide 250k single nucleotide polymorphism array platform. METHODS: Affymetrix 250k NspI single nucleotide polymorphism array analysis (Affymetrix, Inc., Santa Clara, California, USA) was performed on DNA from 38 prenatally karyotyped fetuses with ultrasound anomalies. Analyses were performed after termination of pregnancy, intrauterine fetal death or birth on DNA isolated from fetal or neonatal material. RESULTS: Aberrations were detected in 17 of 38 fetuses, 6 of whom with a previously identified chromosomal abnormality and 11 with previously normal or balanced karyotypes. Of the latter, the detected aberration occurred de novo and was considered of clinical relevance in five cases (16%), inherited from a healthy parent in four cases (12%), and de novo yet with unclear clinical relevance in two cases (6%). The clinically relevant abnormalities either were novel copy number variants (n=3) or concerned a uniparental disomy (n=2). CONCLUSION: In at least 16% of fetuses with ultrasound anomalies and a normal or balanced karyotype, causal (submicroscopic) aberrations were detected, illustrating the importance of the (careful) implementation of microarray analysis in prenatal diagnosis. The fact that the identified, clinically relevant, aberrations would have gone undetected with most targeted approaches underscores the added value of a genome-wide approach. PMID- 20577004 TI - Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huet anomaly. AB - BACKGROUND: Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huet anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huet anomaly (SOPH) syndrome. AIMS: To identify a causative gene for SOPH syndrome. METHODS: Genomewide homozygosity mapping was conducted in 33 patients in 30 families. RESULTS: The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. CONCLUSION: These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huet anomaly. PMID- 20577005 TI - A dominant mesomelic dysplasia associated with a 1.0-Mb microduplication of HOXD gene cluster at 2q31.1. AB - A three-generation family with four patients affected by a novel mesomelic dysplasia was investigated for genome-wide DNA copy number variation profiles. This revealed a microduplication of a 1.0-Mb chromosomal segment at 2q31.1 spanning nine Homeo box D (HOXD) genes that co-segregated with the phenotype. Quantitative PCR analysis of a gene within this duplicated region showed consistent results. Mesomelic dysplasia Kantaputra type (MDK; MIM 156232),which shares some phenotypes with this family, has also been mapped to a chromosomal region comprising 2q31.1, raising the possibility that MDK and the condition observed in this family may be allelic. PMID- 20577006 TI - Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. AB - BACKGROUND: Mutations in TRPV4, a gene that encodes a Ca(2+) permeable non selective cation channel, have recently been found in a spectrum of skeletal dysplasias that includes brachyolmia, spondylometaphyseal dysplasia, Kozlowski type (SMDK) and metatropic dysplasia (MD). Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear. OBJECTIVES AND METHODS: To examine TRPV4 mutation spectrum and phenotype-genotype association, we searched for TRPV4 mutations by PCR-direct sequencing from genomic DNA in 22 MD and 20 SMDK probands. RESULTS: TRPV4 mutations were found in all but one MD subject. In total, 19 different heterozygous mutations were identified in 41 subjects; two were recurrent and 17 were novel. In MD, a recurrent P799L mutation was identified in nine subjects, as well as 10 novel mutations including F471del, the first deletion mutation of TRPV4. In SMDK, a recurrent R594H mutation was identified in 12 subjects and seven novel mutations. An association between the position of mutations and the disease phenotype was also observed. Thus, P799 in exon 15 is a hot codon for MD mutations, as four different amino acid substitutions have been observed at this codon; while R594 in exon 11 is a hotspot for SMDK mutations. CONCLUSION: The TRPV4 mutation spectrum in MD and SMDK, which showed genotype-phenotype correlation and potential functional significance of mutations that are non randomly distributed over the gene, was presented in this study. The results would help diagnostic laboratories establish efficient screening strategies for genetic diagnosis of the TRPV4 dysplasia family diseases. PMID- 20577007 TI - The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor. AB - Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2 has been recently reported as a positive disease modifier. We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotype analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity. PMID- 20577010 TI - Intralipid: having leapt, should we now check the view? PMID- 20577011 TI - Limb loss following intra-arterial drug abuse. PMID- 20577008 TI - Transcobalamin II receptor polymorphisms are associated with increased risk for neural tube defects. AB - OBJECTIVE: Women who have low cobalamin (vitamin B(12)) levels are at increased risk for having children with neural tube defects (NTDs). The transcobalamin II receptor (TCblR) mediates uptake of cobalamin into cells. Inherited variants in the TCblR gene as NTD risk factors were evaluated. METHODS: Case-control and family-based tests of association were used to screen common variation in TCblR as genetic risk factors for NTDs in a large Irish group. A confirmatory group of NTD triads was used to test positive findings. RESULTS: 2 tightly linked variants associated with NTDs in a recessive model were found: TCblR rs2336573 (G220R; p(corr)=0.0080, corrected for multiple hypothesis testing) and TCblR rs9426 (p(corr)=0.0279). These variants were also associated with NTDs in a family-based test before multiple test correction (log-linear analysis of a recessive model: rs2336573 (G220R; RR=6.59, p=0.0037) and rs9426 (RR=6.71, p=0.0035)). A copy number variant distal to TCblR and two previously unreported exonic insertion deletion polymorphisms were described. CONCLUSIONS: TCblR rs2336573 (G220R) and TCblR rs9426 represent a significant risk factor in NTD cases in the Irish population. The homozygous risk genotype was not detected in nearly 1000 controls, indicating that this NTD risk factor may be of low frequency and high penetrance. 9 other variants are in perfect linkage disequilibrium with the associated single nucleotide polymorphisms. Additional work is required to identify the disease-causing variant. Our data suggest that variation in TCblR plays a role in NTD risk and that these variants may modulate cobalamin metabolism. PMID- 20577012 TI - Improved visualisation of a subdural haematoma with the use of reconstructed coronal view images and multi-detector CT. PMID- 20577013 TI - Caecal perforation following apparently minor abdominal blunt trauma. PMID- 20577014 TI - Multiple testing on standardized mortality ratios: a Bayesian hierarchical model for FDR estimation. AB - The analysis of large data sets of standardized mortality ratios (SMRs), obtained by collecting observed and expected disease counts in a map of contiguous regions, is a first step in descriptive epidemiology to detect potential environmental risk factors. A common situation arises when counts are collected in small areas, that is, where the expected count is very low, and disease risks underlying the map are spatially correlated. Traditional p-value-based methods, which control the false discovery rate (FDR) by means of Poisson p-values, might achieve small sensitivity in identifying risk in small areas. This problem is the focus of the present work, where a Bayesian approach which performs a test to evaluate the null hypothesis of no risk over each SMR and controls the posterior FDR is proposed. A Bayesian hierarchical model including spatial random effects to allow for extra-Poisson variability is implemented providing estimates of the posterior probabilities that the null hypothesis of absence of risk is true. By means of such posterior probabilities, an estimate of the posterior FDR conditional on the data can be computed. A conservative estimation is needed to achieve the control which is checked by simulation. The availability of this estimate allows the practitioner to determine nonarbitrary FDR-based selection rules to identify high-risk areas according to a preset FDR level. Sensitivity and specificity of FDR-based rules are studied via simulation and a comparison with p-value-based rules is also shown. A real data set is analyzed using rules based on several FDR levels. PMID- 20577016 TI - Older and swinging; need to identify hidden and emerging risk groups at STI clinics. AB - BACKGROUND: Identification of STI risk groups is essential for optimal prevention and medical care. Until now, swingers--that is, heterosexual couples who are practising mate swapping, group sex, visit sex clubs for couples, are not considered as a specific risk group for STI in healthcare services and prevention. OBJECTIVE: To compare STI prevalence rates in swingers with that in other risk groups. METHODS: At the STI clinic, South Limburg, The Netherlands, whether an attendee is a swinger has been systematically registered since 2007. STI clinic surveillance data were analysed to assess the swingers' share of consultations and STI diagnoses--here Chlamydia trachomatis (CT) and/or Neisseria gonorrhoea (NG). RESULTS: Of 8971 consultations, 12% comprised swingers (median age 43 years, IQR 38-48). Overall, STI prevalence was highest in youth, men who have sex with men (MSM) and swingers. Older swingers had a CT prevalence of 10% and an NG prevalence of 4%. The share in STI diagnoses in the older age group (>45 years) comprised 55% for swingers and 31% for MSM. CONCLUSIONS: Swingers comprise a substantial proportion of STI consultations. They are a mainly older age group and form an important part of STI diagnoses. While other risk groups for STI, such as young heterosexuals and MSM, are systematically identified at STI healthcare facilities and provided with appropriate services, this is generally not the case for swingers. Swingers, like other groups with risk behaviours, need to be identified and treated as a risk group in STI prevention and care. PMID- 20577017 TI - Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener's granulomatosis--a clinical randomized controlled trial. AB - BACKGROUND: The use of plasma exchange (PE) for induction treatment of anti neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV), including Wegener's granulomatosis (WG), is still controversial. The use of PE in AAV is not commonly accepted in patients with a plasma creatinine <500 MUmol/L (5.7 mg/dL) despite experimental support for involvement of ANCA in the pathogenesis of vasculitis. METHODS: In a single-centre study from a tertiary referral centre, 32 patients with ANCA-positive WG were treated with standard immunosuppressive therapy, prednisolone and cyclophosphamide (CYC). In addition, they were randomized to treatment with or without initial PE. After 3 months, they were further randomized in a Latin square design to continue CYC or to change to cyclosporine A (CyA) for 9 months. The renal follow-up was at least 5 years. RESULTS: Renal survival after 1, 3 and 12 months, and 5 years was significantly better in the PE groups. For all groups, the kidney/patient survival was 87.5%/93.7% at 1 year and 72%/56% at 5 years. All patients who were on dialysis when recruited were dialysis dependent 5 years later. There was no difference in morbidity or mortality between PE and control groups. Multivariate analysis demonstrated that PE improved renal survival (P < 0.01) at initial plasma creatinine levels >250 umol/L (2.85 mg/dL). Change from CYC to CyA did not influence rate of relapses or time to relapse. CONCLUSIONS: PE is recommended for induction therapy in WG patients at creatinine levels >250 umol/L (2.85 mg/dL), whereas previous randomized studies have limited PE to patients with creatinine >500 umol/L (5.65 mg/dL). PMID- 20577018 TI - 'Objective Score of Nutrition on Dialysis (OSND) as an alternative for the malnutrition-inflammation score in assessment of nutritional risk of haemodialysis patients'. PMID- 20577019 TI - Translating knowledge into practice and policy: the role of knowledge networks in primary health care. AB - The translation of information into practice is a well-recognised challenge for the health sector. In the primary healthcare sector, the last decade has seen an explosion of information generated by health systems, universities and a range of other sources. Without a system for translating that knowledge into practice and sharing it in a comprehensible form, it will remain meaningless to most practitioners. We propose the establishment of Knowledge Networks as a promising method for supporting the rapid adoption and generation of health information within the primary health care sector to advance health care services. These networks will be particularly important to the implementation of the national reform agenda, responsive decision-making and the translation of new frameworks or competencies into practice. This paper describes how interdisciplinary Knowledge Networks could be established focusing on a number of priority health research areas. Local Knowledge Networks would be used as a platform to support a collaborative web of evidence designed to influence health policy and planning. Our experience with Knowledge Networks indicates that they must be comprised of health professionals from Divisions of General Practice, researchers, policy makers, consumers, government and non-government sectors. This paper will describe these networks and show how they might support the translation of knowledge into practice, thus driving systematic and institutional change. PMID- 20577020 TI - Rethinking health planning: a framework for organising information to underpin collaborative health planning. AB - The field of collaborative health planning faces significant challenges created by the narrow focus of the available information, the absence of a framework to organise that information and the lack of systems to make information accessible and guide decision-making. These challenges have been magnified by the rise of the 'healthy communities movement', resulting in more frequent calls for localised, collaborative and evidence-driven health related decision-making. This paper discusses the role of decision support systems as a mechanism to facilitate collaborative health decision-making. The paper presents a potential information management framework to underpin a health decision support system and describes the participatory process that is currently being used to create an online tool for health planners using geographic information systems. The need for a comprehensive information management framework to guide the process of planning for healthy communities has been emphasised. The paper also underlines the critical importance of the proposed framework not only in forcing planners to engage with the entire range of health determinants, but also in providing sufficient flexibility to allow exploration of the local setting-based determinants of health. PMID- 20577021 TI - Professional practice and innovation: Chronic disease, geographic location and socioeconomic disadvantage as obstacles to equitable access to e-health. AB - Despite recent public attention to e-health as a solution to rising healthcare costs and an ageing population, there have been relatively few studies examining the geographical pattern of e-health usage. This paper argues for an equitable approach to e-health and attention to the way in which e-health initiatives can produce locational health inequalities, particularly in socioeconomically disadvantaged areas. In this paper, we use a case study to demonstrate geographical variation in Internet accessibility, Internet status and prevalence of chronic diseases within a small district. There are significant disparities in access to health information within socioeconomically disadvantaged areas. The most vulnerable people in these areas are likely to have limited availability of, or access to Internet healthcare resources. They are also more likely to have complex chronic diseases and, therefore, be in greatest need of these resources. This case study demonstrates the importance of an equitable approach to e-health information technologies and telecommunications infrastructure. PMID- 20577022 TI - Effects of one-day reperfusion after transient forebrain ischemia on circulatory system in the rat. AB - Although ischemia/reperfusion injury remains incompletely understood, it appears that reactive oxygen species produced mainly during postischemic recirculation play a critical role. The present study examined the impact of forebrain ischemia and subsequent one-day reperfusion on several blood parameters. We determined glutamate concentration in whole blood, measured Cu/Zn- and Mn-SOD (superoxide dismutase) activity in blood cells as well as plasma, and investigated the prevalence of single and double strand breaks of lymphocyte DNA. The results of our experiment showed that the concentration of glutamic acid in whole blood was increased by about 25%. Antioxidant activity of total SOD and Cu/Zn-SOD was reduced in blood cells and plasma. Mn-SOD activity in blood cells was not affected by ischemic insult and one-day reperfusion, but we detected its significantly lower activity in samples of plasma. We observed a weakly reduced level of double and a significantly elevated level of single strand breaks of lymphocyte DNA. In conclusion, one day of recovery after the ischemic attack failed to return peripheral circulatory system to physiological conditions. Reduced antioxidant capacity in the blood and an elevated level of excitotoxic amino acid glutamate may cause lymphocyte DNA damage, and probably contribute to insufficient postischemic recovery of brain tissue. PMID- 20577023 TI - The effect of pH on the activity of soluble peroxidase in needles of Serbian spruce (Picea omorika (Panc.) Purkinye): application of a mathematical model. AB - We studied the dependence of peroxidase (POD) activity on pH in crude extract of Picea omorika (Panc.) Purkinye needles and in its acidic and basic fractions, obtained by ion exchange chromatography. Nonlinear regression was applied on the activity data with pH as the explaining variable, using the Levenberg-Marquardt algorithm. Studying crude extract at three different temperatures, the shape of the simulated activity/pH dependences indicated an existence of two components, which was confirmed by mathematical modeling. The kinetic parameters Act0, KEH and KEOH of both components are presented. The curves and pH optima shifted under increasing temperatures towards lower pH values, which was verified after decomposition. Nonlinear regression detected the presence of two components for both fractions, and there is no considerable difference between their pH optima. Our results show for the first time that the sum of components, each described by the mathematical model employed, can be used to explain the complex pH-related POD activity in the extract with two or more enzyme forms simultaneously active. PMID- 20577024 TI - Analysis of rat papillary muscle transverse deformation by laser diffraction. AB - We use laser diffraction in the analysis of the transversal deformation that the papillary muscle of the female and male Wistar rat may undergo when is subjected to different tension (tension range, 0-30 mN) in the longitudinal plane. Papillary muscles from the right ventricle were illuminated at normal incidence with a He-Ne laser lasing at 594 nm at room temperature. The far-field diffraction pattern projected to a screen was recorded with a digital camera for its analysis. The analysis of the stress-strain curves from the two experimental groups shows that the papillary muscles from male rats exhibit a higher stiffness in the transversal axis compared to the female rats. PMID- 20577025 TI - Effect of selected flavones on cancer and endothelial cells. AB - In our study we used quercetin (3,3 ,4 ,5,7-pentahydroxyflavone) as the reference standard to compare antiproliferative and antiangiogenic effects of chrysin (5,7 dihydroxyflavone) and 3-hydroxyflavone. Our data indicates that chrysin and 3 hydroxyflavone showed significantly higher cytotoxic effect than reference standard quercetin. These tested agents significantly decreased cell survival with the efficacy of 65-85% at the concentration 100 micromol/l for HUVEC, lung carcinoma and leukemic cells being the most sensitive. Cell cycle analysis indicates that quercetin and 3-hydroxyflavone might affect the cell cycle of Jurkat cells by a similar or the same mechanism of action which lead to G2/M arrest as well as to an increase in sub-G0/G1 fraction. Treatment of Jurkat cells with chrysin resulted only increase in the fraction of cells with sub-G0/G1 DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was confirmed by DNA fragmentation and by staining with annexin V. All three tested flavones inhibited endothelial cell migration after 24 h of incubation at a concentration 100 micromol/l. At a lower concentration (10 micromol/l) only quercetin significantly inhibited migration of endothelial cells. Furthermore, in our experiments decreased secretion of matrix metalloproteinases (MMP-2 and MMP 9) was observed after a 72 h treatment with quercetin. No decrease in secretion of MMP-2 and MMP-9 was seen after chrysin and 3-hydroxyflavone treatment. On the other hand, our results showed that none of three flavonoids blocked microcapillary tube formation. Further studies are necessary to investigate the mechanism of action and to find out the relationship between the structure, character and position of substituents of natural substances and their biological activities. PMID- 20577026 TI - Long-term melatonin administration enhances the antioxidant potential of human plasma maintained after discontinuation of the treatment. AB - We investigated the effect of long-term oral melatonin administration on the antioxidant capacity of plasma. The study was performed on healthy volunteers divided into two groups: the control group (without melatonin treatment) and the study group treated with 6 mg of melatonin per day for two weeks, 2 hours before bedtime. Blood samples were drawn: before melatonin administration, on the 7th and 14th day of melatonin treatment and on the 10th day after the last dose of melatonin. It was shown that oral administration of melatonin increases plasma antioxidant ferric reducing ability (FRAP assay) (p<0.05) and DPPH (1,1-diphenyl 2-picrylhydrazyl) radical scavenging (p<0.01), and decreases thiobarbituric acid reactive substances (TBARS) (p<0.05) and DNA damage (p<0.001). This protective effect is maintained for at last 10 days after discontinuation of the treatment. The present work highlights that the antioxidant capacity of plasma was significantly higher on the 10th day after the discontinuation of melatonin treatment than on the 14th day of its administration. Our findings indicated that a long-term oral melatonin administration maintained the increased antioxidant capacity of plasma and prevented oxidative damage to DNA after hormone administration was discontinued. PMID- 20577027 TI - Desmopressin stimulates bile secretion in anesthetized rats. AB - One of the synthetic analogues of antidiuretic hormone-desmopressin is used in patients with central diabetes insipidus and in those with coagulation disorders. However, its effects on bile secretion are not fully defined. We investigated the effect of desmopressin on bile formation and determined the role of V1a vasopressin receptors in the action of desmopressin on choleresis. Rats were injected intraportally with a bolus of desmopressin; the changes of bile flow, the content of free and conjugated cholates were compared with control animal group. Selective antagonist of V1a receptors was injected 10 minutes before desmopressin treatment and the findings were compared with the results after desmopressin injection alone. Desmopressin increased bile flow, secretion of total cholates like amino acids conjugated, while diminished free bile acids content. Secreted bile volume and conjugated bile acids content were reduced in V1a receptors antagonist+desmopressin-treated rats. In contrast, free bile acids content was more than the results in desmopressin-treated rats. Desmopressin at concentrations nearly equal to physiological concentrations of natural hormone in blood shows its choleretic effect. Antagonist of V1a vasopressin receptors modulates desmopressin action. This certifies the role of these receptors in the action of desmopressin on different processes of bile formation. PMID- 20577028 TI - Mouse and human mitochondrial nucleoid--detailed structure in relation to function. AB - The independent mitochondrial genetic information is organized in so-called mitochondrial nucleoids that, in vertebrates, typically contain 5-7 genetic units. The total number of nucleoids per cell is several hundred in cultured cells. Mitochondrial nucleoids, similarly to the whole mitochondrial network, have recently been successfully and extensively visualized using fluorescent and confocal microscopy. In the present work, we show high-resolution micrographs of mouse and human mitochondrial nucleoids obtained by transmission electron microscopy. Position in the mitochondria, size, general appearance and other properties of the human nucleoids appear the same as those of mouse nucleoids, and all observations are also in full agreement with the results obtained in different laboratories using different approaches. Most of nucleoids are located inside mitochondrial tubes. However, we show directly that certain part of the nucleoids close to inner membrane is bound to the complex of molecules that crosscut both, the inner and the outer mitochondrial membranes. Nucleoids in cells starving for serum are mostly more dense than those in dividing cells. We discuss the position, appearance and other properties of the nucleoids in relation to functional stage. Other electron-dense structures inside mitochondria that could be erroneously considered to be mitochondrial nucleoids are also described. PMID- 20577029 TI - The binding affinity of carcinogenic N-nitrosodimethylamine and N nitrosomethylaniline to cytochromes P450 2B4, 2E1 and 3A6 does not dictate the rate of their enzymatic N-demethylation. AB - The interaction of carcinogenic N-nitrosodimethylamine (NDMA) and N nitrosomethylaniline (NMA) with cytochromes P450 (CYP), CYP2B4, CYP2E1 and CYP3A6, and their metabolism by these enzymes reconstituted with NADPH-CYP reductase in liposomes were studied. Using the difference spectroscopy, the lowest values of spectral dissociation constants (KS) of the binary complex of NDMA and NMA with the enzyme were found for CYP2E1. Both N-nitrosamines bind to the heme iron atom as ligands. On the contrary, the binding of NDMA and NMA to CYP2B4 gives the type I spectra. NDMA is bound to CYP3A6 analogously as to CYP2B4, whereas no difference spectra were acquired with NMA and CYP3A6. All tested CYPs oxidize NDMA and NMA. CYP2E1 exhibits the lowest Km values, 7.5 and 5.0 micromol/l for NDMA and NMA, respectively, and for CYP3A6 we found 30.0 and 10.0 micromol/l for NDMA and NMA, respectively, while CYP2B4 exhibits the lowest affinity for both carcinogens. In spite of different binding affinities of NDMA and NMA, the values of Vmax for their oxidation were, however, similar for all tested CYPs. The results demonstrate that investigations utilizing several enzymatic approaches are necessary to properly evaluate the mechanism and efficiency of NDMA and NMA oxidation by CYPs in vitro. PMID- 20577030 TI - May modifications of human plasma proteins stimulated by homocysteine and its thiolactone induce changes of hemostatic function of plasma in vitro? AB - Homocysteine (Hcys) may be implicated in different diseases, especially in cardiovascular illnesses. The most reactive form of Hcys is its cyclic thioester homocysteine thiolactone (HTL), which is formed in plasma and represents up to 0.29% of plasma total Hcys. Recently, it has been observed that Hcys and HTL may modify plasma proteins, including albumin, hemoglobin or fibrinogen, but the role of this process is not yet well known. The aim of our study in vitro was to investigate the modifications of human plasma total proteins after incubation with the reduced form of Hcys in concentrations 10-100 micromol/l, and HTL in concentrations 1-0.1 micromol/l, which correspond to levels found in human plasma during hyperhomocysteinemia in vivo. The aim of our study was also to explain the effects of Hcys and HTL on coagulation activity of human plasma. We showed that in model system in vitro Hcys and HTL change the level of thiol, amino and carbonyl groups in plasma total proteins. Moreover, our studies reported that not only Hcys (10-100 micromol/l), but also HTL (at lower concentrations than Hcys) modulates the coagulation properties of human plasma. PMID- 20577031 TI - Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study. AB - Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal. PMID- 20577032 TI - Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment. AB - Effect of captopril treatment on capability of heart and kidney mitochondria to produce ATP was investigated in spontaneously hypertensive rats (SHR). Heart mitochondria from SHR responded to hypertension with tendency to compensate the elevated energy demands of cardiac cells by moderate increase in mitochondrial Mg2+-ATPase activity, membrane fluidity (MF) and in majority of functional parameters of the mitochondria (p>0.05). Significant increase exhibited only the oxygen consumption (QO2; p<0.01-0.001) and oxidative phosphorylation rate (OPR; p<0.003) with glutamate+malate (GLUT+MAL) as substrates. Lowering the blood pressure (p<0.02) captopril also eliminated the above compensatory response and impaired the oxidative ATP production by decreasing OPR (p<0.001). Kidney mitochondria of SHR experienced serious disarrangement in parameters of oxidative ATP production: increase in Mg2+-ATPase activity (p<0.05) but, also scattered QO2 values (p<0.03-0.01) leading to decrease in OPR and the ADP:O (p<0.05-0.01) values with both GLUT+MAL and succinate as substrates. Captopril treatment does not alleviated but even worsened the above alterations. Mg2+-ATPase became also decreased and the depression of ADP:O became aggravated (p<0.0001). PMID- 20577033 TI - The lipid peroxidation in breast cancer patients. AB - The aim of our study was to estimate oxidative stress (by using different biomarkers of lipid peroxidation--isoprostanes and thiobarbituric acid reactive substances (TBARS)) in patients with invasive breast cancer, patients with benign breast diseases and in a control group. We observed a statistically increased level of TBARS in plasma and isoprostanes in urine of patients with invasive breast cancer in comparison with a control group. The concentration of tested biomarkers in plasma or urine from patients with invasive breast cancer was also higher than in patients with benign breast diseases. Moreover, the levels of tested markers in patients with benign breast diseases and in a control group did not differ. Considering the data presented in this study, we suggest that free radicals induce peroxidation of unsaturated fatty acid in patients with breast cancer. PMID- 20577034 TI - Entropy measurements in paroxysmal and persistent atrial fibrillation. AB - Recent studies on atrial fibrillation (AF) have identified different activation patterns in paroxysmal and persistent AF. In this study, bipolar intra-atrial registers from 28 patients (14 paroxysmal AF and 14 persistent AF) were analyzed in order to find out regional differences in the organization in both types of arrhythmias. The organization of atrial electrical activity was assessed in terms of nonlinear parameters, such as entropy measurements. Results showed differences between the atrial chambers with a higher disorganization in the left atrium in paroxysmal AF patients and a more homogenous behavior along the atria in persistent AF patients. PMID- 20577035 TI - Electrical impedance characterization of normal and cancerous human hepatic tissue. AB - The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m( 1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation. PMID- 20577036 TI - Quantum science and technology at the nanoscale. PMID- 20577038 TI - Enhanced accuracy of the permanent surveillance of IMRT deliveries by iterative deconvolution of DAVID chamber signal profiles. AB - In vivo dosimetry systems, capable of permanently monitoring IMRT treatment deliveries throughout all fractions, are increasingly used in clinical practice. The first of these solutions is the DAVID system, a translucent multiwire ionization chamber placed in the accessory holder of the treatment head below the MLC. Each wire is exactly adjusted along the midline of its associated leaf pair, thereby generating a signal correlated with the aperture of this leaf pair. However, there is some blurring of the profile of the wire signals across the beam due to the lateral transport of scattered secondary electrons in the air gap of the DAVID chamber. This paper deals with a numerical correction by which this effect is eliminated. The true photon fluence profile is calculated from the measured signal profile by an iterative deconvolution algorithm, based upon the convolution kernel formed by the lateral wire signal profile when only one leaf pair is opened. Lateral fluence profiles are thereby obtained with increased resolution, and errors in MLC positioning are revealed with enhanced sensitivity. The needed computational time of less than 1 s has made it feasible to implement the deconvolution algorithm into the daily routine for the accurate surveillance of IMRT deliveries. PMID- 20577037 TI - Coarse-graining RNA nanostructures for molecular dynamics simulations. AB - A series of coarse-grained models have been developed for study of the molecular dynamics of RNA nanostructures. The models in the series have one to three beads per nucleotide and include different amounts of detailed structural information. Such a treatment allows us to reach, for systems of thousands of nucleotides, a time scale of microseconds (i.e. by three orders of magnitude longer than in full atomistic modeling) and thus to enable simulations of large RNA polymers in the context of bionanotechnology. We find that the three-beads-per-nucleotide models, described by a set of just a few universal parameters, are able to describe different RNA conformations and are comparable in structural precision to the models where detailed values of the backbone P-C4' dihedrals taken from a reference structure are included. These findings are discussed in the context of RNA conformation classes. PMID- 20577039 TI - Skin age testing criteria: characterization of human skin structures by 500 MHz MRI multiple contrast and image processing. AB - Ex vivo magnetic resonance microimaging (MRM) image characteristics are reported in human skin samples in different age groups. Human excised skin samples were imaged using a custom coil placed inside a 500 MHz NMR imager for high-resolution microimaging. Skin MRI images were processed for characterization of different skin structures. Contiguous cross-sectional T1-weighted 3D spin echo MRI, T2 weighted 3D spin echo MRI and proton density images were compared with skin histopathology and NMR peaks. In all skin specimens, epidermis and dermis thickening and hair follicle size were measured using MRM. Optimized parameters TE and TR and multicontrast enhancement generated better MRI visibility of different skin components. Within high MR signal regions near to the custom coil, MRI images with short echo time were comparable with digitized histological sections for skin structures of the epidermis, dermis and hair follicles in 6 (67%) of the nine specimens. Skin % tissue composition, measurement of the epidermis, dermis, sebaceous gland and hair follicle size, and skin NMR peaks were signatures of skin type. The image processing determined the dimensionality of skin tissue components and skin typing. The ex vivo MRI images and histopathology of the skin may be used to measure the skin structure and skin NMR peaks with image processing may be a tool for determining skin typing and skin composition. PMID- 20577040 TI - Numerical study of oxygen transport in a carotid bifurcation. AB - This study investigates the oxygen mass transport in the region around the human carotid bifurcation, particularly addressing the effects of bifurcation geometry and pulsatile blood flow on the oxygen transport between the blood flow and artery wall tissue, coupled with the metabolic oxygen consumption and oxygen diffusion in the artery wall tissue. The temporal variations and spatial distributions of the oxygen tension are predicted quantitatively using a geometric model of the human carotid bifurcation and realistic blood flow waveforms. Results reveal that the flow separation at the outside wall of the sinus of the internal carotid artery (ICA) can markedly alter the flow pattern, oxygen tension and the oxygen wall flux. Results also clarify that the flow unsteadiness has a secondary effect on the oxygen tension inside the wall. The non-dimensional oxygen flux, the Sherwood number Sh, at the outside wall of the ICA sinus, takes markedly lower values of about 45 than at other sites because the rates of oxygen transport by the convective flow are reduced at the outside wall of the ICA sinus. The transverse distributions of the oxygen tension inside the artery wall show parabolic profiles having minima in the middle of the wall thickness, with the lowest value of 35 mmHg. These predicted distributions of the oxygen tension inside the wall closely resemble those obtained from experiments. The results demonstrate that hypoxic zones appear inside the artery walls at locations where atherosclerotic lesions are prone to develop. PMID- 20577041 TI - Experimental study on photon-beam peripheral doses, their components and some possibilities for their reduction. AB - The component analysis of the peripheral doses produced at typical accelerators such as the Siemens Primus 6/15 is regarded as an approach enabling technical strategies towards the reduction of second malignancies associated with photon beam radiotherapy. Suitable phantom and detector arrangements have been applied to show that the unavoidable peripheral dose contribution due to photon scattering from the directly irradiated part of the body or phantom does not constitute the entirety of the peripheral doses. Rather, there are peripheral dose contributions due to beam head leakage and to extrafocal radiation which can be regarded as partly avoidable. Simple methods of reducing beam head leakage from the Siemens Primus 6/15 linac are, for the crossplane direction, to install a pair of adjustable shielding blocks in the accessory holder and, for the inplane direction, to close all out-of-field leaf pairs of the multileaf collimator via the treatment planning system software. The relative efficiency of these shielding measures is largest in the case of small unavoidable dose contributions, i.e. for small fields and small depths. Methods of avoiding doses coming from extrafocal radiation are also envisaged for future research. PMID- 20577042 TI - A comprehensive method for optical-emission computed tomography. AB - Optical-computed tomography (CT) and optical-emission computed tomography (ECT) are recent techniques with potential for high-resolution multi-faceted 3D imaging of the structure and function in unsectioned tissue samples up to 1-4 cc. Quantitative imaging of 3D fluorophore distribution (e.g. GFP) using optical-ECT is challenging due to attenuation present within the sample. Uncorrected reconstructed images appear hotter near the edges than at the center. A similar effect is seen in SPECT/PET imaging, although an important difference is attenuation occurs for both emission and excitation photons. This work presents a way to implement not only the emission attenuation correction utilized in SPECT, but also excitation attenuation correction and source strength modeling which are unique to optical-ECT. The performance of the correction methods was investigated by the use of a cylindrical gelatin phantom whose central region was filled with a known distribution of attenuation and fluorophores. Uncorrected and corrected reconstructions were compared to a sectioned slice of the phantom imaged using a fluorescent dissecting microscope. Significant attenuation artifacts were observed in uncorrected images and appeared up to 80% less intense in the central regions due to attenuation and an assumed uniform light source. The corrected reconstruction showed agreement throughout the verification image with only slight variations ( approximately 5%). Final experiments demonstrate the correction in tissue as applied to a tumor with constitutive RFP. PMID- 20577043 TI - Radioprotection: smart games with death. AB - The efficacy of cancer treatment by radiation and chemotherapeutic drugs is often limited by severe side effects that primarily affect the hematopoietic system and the epithelium of the gastrointestinal tract. Progress in understanding differences in the mechanisms involved in the responses of normal and tumor cells to genotoxic stress has led to the development of new rational approaches to selective protection of normal cells, such as suppression of apoptosis by pharmacological inhibition of p53 or activation of NF-kappaB. Another promising approach presented in this issue by Johnson et al. is based on the idea of using pharmacological inhibitors of cyclin-dependent kinases (CDKs) to convert normal cells into a radioresistant state by inducing reversible cell cycle arrest at the G1/S transition. The evidence indicates that this approach is likely to be specific for protection of normal cells and may, therefore, have clinical potential as an adjuvant in anticancer therapies. PMID- 20577044 TI - A balancing act for autophagin. AB - Autophagy is a tightly regulated catabolic process whereby cells degrade their constituents to dispose of unwanted cytoplasmic elements and recycle nutrients for cellular remodeling. Studies of autophagy in mammals have elicited substantial interest because it is linked to a range of physiologic and pathologic states. In this issue of the JCI, Marino et al. uncover a role for autophagy in a balance disorder related to inner ear pathologies. Mice lacking the protease autophagy-related 4B (Atg4b, also known as autophagin-1) exhibited a systemic reduction in autophagy and showed defects in the development of otoconia, organic particles that contain calcium carbonate crystals and proteins and that are essential for balance perception (equilibrioception) in mammals. The intriguing aspect of this work is that an autophagy block impairs the secretion and assembly of otoconial proteins, emphasizing a role for autophagy in functions distinct from macromolecule degradation. PMID- 20577045 TI - Rapid progress for non-nuclear estrogen receptor signaling. AB - Estrogen receptors are best known as ligand-activated transcription factors that regulate vascular cell gene expression. For many years now, a rapid signaling pathway mediated by cell membrane-associated estrogen receptors also has been recognized, but the physiological relevance of this pathway has remained unclear. In this issue of the JCI, Chambliss et al. provide new data to indicate that activation of non-nuclear estrogen receptor signaling regulates processes central to cardiovascular health and disease. These investigators show that an estrogen dendrimer conjugate (EDC), which activates estrogen receptors but remains non nuclear, stimulates vascular EC migration in vitro and protects against vascular injury in vivo. They show further that the vascular benefits of EDC in vivo occur selectively in the vasculature, without stimulating the uterus or enhancing growth of breast cancer xenografts. Taken together, these findings indicate that activation of non-nuclear estrogen receptor signaling regulates vascular events of physiological relevance and suggest that translation of these findings into clinically relevant therapeutic interventions is a logical next goal. PMID- 20577046 TI - An energetic tale of AMPK-independent effects of metformin. AB - Metformin has become a mainstay in the modest therapeutic armamentarium for the treatment of the insulin resistance of type 2 diabetes mellitus. Although metformin functions primarily by reducing hepatic glucose output, the molecular mechanism mediating this effect had remained elusive until recently. Metformin impairs ATP production, activating the conserved sensor of nutritional stress AMP activated protein kinase (AMPK), thus providing a plausible and generally accepted model for suppression of gluconeogenic gene expression and glucose output. In this issue of the JCI, Foretz et al. refute this hypothesis by showing that AMPK is dispensable for the effects of metformin on hepatic glucose output in primary hepatocytes; rather, their data suggest that the antidiabetic effects of metformin in the liver are mediated directly by reducing energy charge. PMID- 20577048 TI - Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-beta signaling in hepatic stellate cells. AB - PDGF-dependent hepatic stellate cell (HSC) recruitment is an essential step in liver fibrosis and the sinusoidal vascular changes that accompany this process. However, the mechanisms that regulate PDGF signaling remain incompletely defined. Here, we found that in two rat models of liver fibrosis, the axonal guidance molecule neuropilin-1 (NRP-1) was upregulated in activated HSCs, which exhibit the highly motile myofibroblast phenotype. Additionally, NRP-1 colocalized with PDGF-receptor beta (PDGFRbeta) in HSCs both in the injury models and in human and rat HSC cell lines. In human HSCs, siRNA-mediated knockdown of NRP-1 attenuated PDGF-induced chemotaxis, while NRP-1 overexpression increased cell motility and TGF-beta-dependent collagen production. Similarly, mouse HSCs genetically modified to lack NRP-1 displayed reduced motility in response to PDGF treatment. Immunoprecipitation and biochemical binding studies revealed that NRP-1 increased PDGF binding affinity for PDGFRbeta-expressing cells and promoted downstream signaling. An NRP-1 neutralizing Ab ameliorated recruitment of HSCs, blocked liver fibrosis in a rat model of liver injury, and also attenuated VEGF responses in cultured liver endothelial cells. In addition, NRP-1 overexpression was observed in human specimens of liver cirrhosis caused by both hepatitis C and steatohepatitis. These studies reveal a role for NRP-1 as a modulator of multiple growth factor targets that regulate liver fibrosis and the vascular changes that accompany it and may have broad implications for liver cirrhosis and myofibroblast biology in a variety of other organ systems and disease conditions. PMID- 20577047 TI - Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice. AB - Steroid hormone receptors function classically in the nucleus as transcription factors. However, recent data indicate that there are also non-nuclear subpopulations of steroid hormone receptors, including estrogen receptors (ERs), that mediate membrane-initiated signaling of unclear basis and significance. Here we have shown that an estrogen-dendrimer conjugate (EDC) that is excluded from the nucleus stimulates endothelial cell proliferation and migration via ERalpha, direct ERalpha-Galphai interaction, and endothelial NOS (eNOS) activation. Analysis of mice carrying an estrogen response element luciferase reporter, ER regulated genes in the mouse uterus, and eNOS enzyme activation further indicated that EDC specifically targets non-nuclear processes in vivo. In mice, estradiol and EDC equally stimulated carotid artery reendothelialization in an ERalpha- and G protein-dependent manner, and both agents attenuated the development of neointimal hyperplasia following endothelial injury. In contrast, endometrial carcinoma cell growth in vitro and uterine enlargement and MCF-7 cell breast cancer xenograft growth in vivo were stimulated by estradiol but not EDC. Thus, EDC is a non-nuclear selective ER modulator (SERM) in vivo, and in mice, non nuclear ER signaling promotes cardiovascular protection. These processes potentially could be harnessed to provide vascular benefit without increasing the risk of uterine or breast cancer. PMID- 20577049 TI - Identification and validation of genes affecting aortic lesions in mice. AB - Atherosclerosis represents the most significant risk factor for coronary artery disease (CAD), the leading cause of death in developed countries. To better understand the pathogenesis of atherosclerosis, we applied a likeli-hood-based model selection method to infer gene-disease causality relationships for the aortic lesion trait in a segregating mouse population demonstrating a spectrum of susceptibility to developing atherosclerotic lesions. We identified 292 genes that tested causal for aortic lesions from liver and adipose tissues of these mice, and we experimentally validated one of these candidate causal genes, complement component 3a receptor 1 (C3ar1), using a knockout mouse model. We also found that genes identified by this method overlapped with genes progressively regulated in the aortic arches of 2 mouse models of atherosclerosis during atherosclerotic lesion development. By comparing our gene set with findings from public human genome-wide association studies (GWAS) of CAD and related traits, we found that 5 genes identified by our study overlapped with published studies in humans in which they were identified as risk factors for multiple atherosclerosis related pathologies, including myocardial infarction, serum uric acid levels, mean platelet volume, aortic root size, and heart failure. Candidate causal genes were also found to be enriched with CAD risk polymorphisms identified by the Wellcome Trust Case Control Consortium (WTCCC). Our findings therefore validate the ability of causality testing procedures to provide insights into the mechanisms underlying atherosclerosis development. PMID- 20577050 TI - Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. AB - Jet lag encompasses a range of psycho- and physiopathological symptoms that arise from temporal misalignment of the endogenous circadian clock with external time. Repeated jet lag exposure, encountered by business travelers and airline personnel as well as shift workers, has been correlated with immune deficiency, mood disorders, elevated cancer risk, and anatomical anomalies of the forebrain. Here, we have characterized the molecular response of the mouse circadian system in an established experimental paradigm for jet lag whereby mice entrained to a 12-hour light/12-hour dark cycle undergo light phase advancement by 6 hours. Unexpectedly, strong heterogeneity of entrainment kinetics was found not only between different organs, but also within the molecular clockwork of each tissue. Manipulation of the adrenal circadian clock, in particular phase-shifting of adrenal glucocorticoid rhythms, regulated the speed of behavioral reentrainment. Blocking adrenal corticosterone either prolonged or shortened jet lag, depending on the time of administration. This key role of adrenal glucocorticoid phasing for resetting of the circadian system provides what we believe to be a novel mechanism-based approach for possible therapies for jet lag and jet lag associated diseases. PMID- 20577051 TI - Myeloperoxidase-rich Ly-6C+ myeloid cells infiltrate allografts and contribute to an imaging signature of organ rejection in mice. AB - Rates of graft rejection are high among recipients of heart transplants. The onset and progression of clinically significant heart transplant rejection are currently monitored by serial biopsy, but this approach is highly invasive and lacks sensitivity. Here, we have developed what we believe to be a new technique to measure organ rejection noninvasively that involves the exploration of tissue infiltrating leukocytes as biomarker sources for diagnostic imaging. Specifically, we profiled the myeloid response in a murine model of heart transplantation with the aim of defining and validating an imaging signature of graft rejection. Ly-6Chi monocytes, which promote inflammation, accumulated progressively in allografts but only transiently in isografts. Ly-6Clo monocytes, which help resolve inflammation, did not accumulate, although they composed the majority of the few remaining monocytes in isografts. The persistence of Ly-6Chi monocytes in allografts prompted us to screen for a Ly-6Chi monocyte-associated imaging marker. Low-density array data revealed that Ly-6Chi monocytes express 10 fold higher levels of myeloperoxidase (MPO) than Ly-6Clo monocytes. Noninvasive magnetic resonance imaging of MPO with an MPO-activatable Gd-chelate revealed a spatially defined T1-weighted signal in rejected allografts but not in isografts or MPO-deficient allograft recipients. Flow cytometry, enzymography, and histology validated the approach by mapping MPO activity to Ly-6Chi monocytes and neutrophils. Thus, MPO imaging represents a potential alternative to the current invasive clinical standard by which transplants are monitored. PMID- 20577052 TI - Autophagy is essential for mouse sense of balance. AB - Autophagy is an evolutionarily conserved process that is essential for cellular homeostasis and organismal viability in eukaryotes. However, the extent of its functions in higher-order processes of organismal physiology and behavior is still unknown. Here, we report that autophagy is essential for the maintenance of balance in mice and that its deficiency leads to severe balance disorders. We generated mice deficient in autophagin-1 protease (Atg4b) and showed that they had substantial systemic reduction of autophagic activity. Autophagy reduction occurred through defective proteolytic processing of the autophagosome component LC3 and its paralogs, which compromised the rate of autophagosome maturation. Despite their viability, Atg4b-null mice showed unusual patterns of behavior that are common features of inner ear pathologies. Consistent with this, Atg4b-null mice showed defects in the development of otoconia, organic calcium carbonate crystals essential for sense of balance (equilibrioception). Furthermore, these abnormalities were exacerbated in Atg5-/- mice, which completely lack the ability to perform autophagy, confirming that autophagic activity is necessary for otoconial biogenesis. Autophagy deficiency also led to impaired secretion and assembly of otoconial core proteins, thus hampering otoconial development. Taken together, these results describe an essential role for autophagy in inner ear development and equilibrioception and open new possibilities for understanding and treating human balance disorders, which are of growing relevance among the elderly population. PMID- 20577053 TI - Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. AB - Metformin is widely used to treat hyperglycemia in individuals with type 2 diabetes. Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis. However, the molecular mechanism by which this pathway operates had remained elusive. Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained. Hepatocytes lacking AMPK displayed normal glucose production and gluconeogenic gene expression compared with wild-type hepatocytes. In contrast, gluconeogenesis was upregulated in LKB1-deficient hepatocytes. Metformin decreased expression of the gene encoding the catalytic subunit of glucose-6-phosphatase (G6Pase), while cytosolic phosphoenolpyruvate carboxykinase (Pepck) gene expression was unaffected in wild-type, AMPK deficient, and LKB1-deficient hepatocytes. Surprisingly, metformin-induced inhibition of glucose production was amplified in both AMPK- and LKB1-deficient compared with wild-type hepatocytes. This inhibition correlated in a dose dependent manner with a reduction in intracellular ATP content, which is crucial for glucose production. Moreover, metformin-induced inhibition of glucose production was preserved under forced expression of gluconeogenic genes through PPARgamma coactivator 1alpha (PGC-1alpha) overexpression, indicating that metformin suppresses gluconeogenesis via a transcription-independent process. In conclusion, we demonstrate that metformin inhibits hepatic gluconeogenesis in an LKB1- and AMPK-independent manner via a decrease in hepatic energy state. PMID- 20577054 TI - Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. AB - Total body irradiation (TBI) can induce lethal myelosuppression, due to the sensitivity of proliferating hematopoietic stem/progenitor cells (HSPCs) to ionizing radiation (IR). No effective therapy exists to mitigate the hematologic toxicities of TBI. Here, using selective and structurally distinct small molecule inhibitors of cyclin-dependent kinase 4 (CDK4) and CDK6, we have demonstrated that selective cellular quiescence increases radioresistance of human cell lines in vitro and mice in vivo. Cell lines dependent on CDK4/6 were resistant to IR and other DNA-damaging agents when treated with CDK4/6 inhibitors. In contrast, CDK4/6 inhibitors did not protect cell lines that proliferated independently of CDK4/6 activity. Treatment of wild-type mice with CDK4/6 inhibitors induced reversible pharmacological quiescence (PQ) of early HSPCs but not most other cycling cells in the bone marrow or other tissues. Selective PQ of HSPCs decreased the hematopoietic toxicity of TBI, even when the CDK4/6 inhibitor was administered several hours after TBI. Moreover, PQ at the time of administration of therapeutic IR to mice harboring autochthonous cancers reduced treatment toxicity without compromising the therapeutic tumor response. These results demonstrate an effective method to mitigate the hematopoietic toxicity of IR in mammals, which may be potentially useful after radiological disaster or as an adjuvant to anticancer therapy. PMID- 20577055 TI - Location, location, location: important for jet-lagged circadian loops. AB - It is now believed that frequent jet lag or shifts of daily rhythms caused by rotating shift work can lead to deleterious health outcomes. Indeed, many serious health problems, including breast cancer, stroke, and cardiovascular disease, have been linked to an occupational history of shift work. This has heightened interest in better understanding the biological responses to jet lag and shift work, with the hope that this will pave the way to developing compounds that can help people avoid their negative health consequences. In this context, a report in this issue of the JCI takes us to a new level of understanding of the molecular control of the resetting of the multitude of internal biological clocks disrupted in a mouse model of jet lag. PMID- 20577056 TI - Medical hazards of prolonged sitting. PMID- 20577057 TI - Why doesn't weight gain blunt appetite and increase movement? Nonhomeostatic responses to energy surplus in humans. PMID- 20577058 TI - Too much sitting: the population health science of sedentary behavior. AB - Even when adults meet physical activity guidelines, sitting for prolonged periods can compromise metabolic health. Television (TV) time and objective measurement studies show deleterious associations, and breaking up sedentary time is beneficial. Sitting time, TV time, and time sitting in automobiles increase premature mortality risk. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required. PMID- 20577059 TI - Nonhomeostatic control of human appetite and physical activity in regulation of energy balance. AB - Ghrelin and leptin, putative controllers of human appetite, have no effect on human meal-to-meal appetite but respond to variations in energy availability. Nonhomeostatic characteristics of appetite and spontaneous activity stem from inhibition by leptin and ghrelin of brain reward circuit that is responsive to energy deficit, but refractory in obesity, and from the operation of a meal timing circadian clock. PMID- 20577061 TI - Epimuscular myofascial force transmission implies novel principles for muscular mechanics. AB - In addition to the myotendinous junctions, muscle fibers also are connected to the extracellular matrix along their full peripheral length. Moreover, within the in vivo context, muscle is not an isolated entity. Instead, myofascial tissues connect muscles mechanically to neighboring muscular and nonmuscular structures, epimuscularly. This paper reviews the key aspects, determinants, and effects of epimuscular myofascial force transmission on muscular mechanics. PMID- 20577060 TI - Postexercise hypotension: central mechanisms. AB - A single bout of exercise can lead to a postexercise decrease in blood pressure in hypertensive individuals, called postexercise hypotension. Compelling evidence suggests that the central baroreflex pathway plays a crucial role in the development of postexercise hypotension. This review focuses on the exercise induced changes in brainstem nuclei involved in blood pressure regulation. PMID- 20577062 TI - Excitation-contraction coupling and minor triadic proteins in low-frequency fatigue. AB - Low-frequency fatigue (LFF) is characterized by a proportionally greater loss of force at low compared with high activation frequencies and a prolonged recovery. Recent work suggests a calcium-induced uncoupling of excitation-contraction coupling underlies LFF. Here, newly characterized triadic proteins are described, and possible mechanisms by which they may contribute to LFF are suggested. PMID- 20577063 TI - Ankle sprains: getting off on the wrong foot. AB - In research on the role of reflexes in ankle sprains, most attention has traditionally gone toward perturbed standing and toward spindle afferents from the peroneal muscles. It is argued that other paradigms are needed that are more closely related to sports. In addition, the role of other afferents (e.g., from skin) and other muscles (from upper leg) should be considered. PMID- 20577064 TI - Acute contaminated open forearm fractures treated with VersaJet Hydrosurgical Debridement. AB - The ideal method of irrigation and debridement for severe extremity wounds has yet to be determined. This report demonstrates the use of hydrosurgical debridement in the treatment of highly contaminated acute forearm fractures in a 22-year-old man ejected during a motor vehicle crash in a farm area. The result was rapid, selective, and effective debridement of deeply embedded material, which allowed for expeditious reconstruction with internal fixation, tendon transfers, and groin flap coverage while avoiding infection and injury to vital structures. The technique is described in detail and the current literature is reviewed. PMID- 20577065 TI - Failure of internal fixation of a humerus fracture resulting from longitudinal fissuring: a case report. AB - We present the case of failure of internal fixation of a humerus fracture resulting from longitudinal fissuring of the far cortex from linearly placed screws. Our case involves a 60-year-old right hand-dominant male who underwent open reduction and internal fixation of a left midshaft humerus fracture (Orthopaedic Trauma Association Type 12-B2) with an ipsilateral Bado Type I Monteggia fracture after being struck by a motor vehicle while crossing the street. Our patient's fixation subsequently failed, which was found intraoperatively to be caused by a stress riser along the far cortex from linearly place screws. PMID- 20577066 TI - "Medial migration of lag screw with intrapelvic dislocation in Gamma nailing--a unique problem? A report of two cases". PMID- 20577067 TI - Is ulnar nerve transposition beneficial during open reduction internal fixation of distal humerus fractures? AB - OBJECTIVES: The purpose of this study was to compare the incidence of ulnar neuritis with and without ulnar nerve transposition during open reduction and internal fixation (ORIF) of distal humerus fractures. DESIGN: Multicenter retrospective cohort series. SETTING: : Two Level I trauma centers. PATIENTS: Two cohorts were identified: 89 patients (mean age, 48.6 years) who had not undergone an ulnar nerve transposition and 48 patients (mean age, 43.2 years) who had undergone a transposition during ORIF of a distal humerus fracture (Orthopaedic Trauma Association 13A or 13C). INTERVENTION: All patients underwent ORIF of a distal humerus fracture with or without anterior subcutaneous ulnar nerve transposition based on surgeon preference. MAIN OUTCOME MEASURE: Presence or absence of ulnar neuritis (ulnar-sided paresthesias, numbness, or intrinsic weakness) or reoperation related to ulnar nerve symptoms. RESULTS: : Average follow up was 9.6 months in the transposition group and 16.0 months in the nontransposition group. Transposition of the ulnar nerve was found to be an independent variable associated with ulnar neuritis (P < 0.001). The incidence of ulnar neuritis was 33% (16 of 48) with transposition and 9% (eight of 89) without transposition (P = 0.0003). Of the patients with ulnar neuritis, one patient in the nontransposition group (1%) and two patients in the transposition group (4%) required additional surgery specifically related to the ulnar nerve. One patient who had undergone transposition developed chronic motor and sensory denervation. CONCLUSION: Patients who underwent ulnar nerve transposition at the time of ORIF of distal humerus fractures had almost four times the incidence of ulnar neuritis than those without transposition. We do not recommend routine transposition of the ulnar nerve at the time of ORIF of distal humerus fractures. PMID- 20577068 TI - Fate of the ulnar nerve after operative fixation of distal humerus fractures. AB - OBJECTIVES: It is well recognized that operative treatment of a fracture of the distal humerus requires handling of the ulnar nerve, which can cause nerve dysfunction; however, the incidence of postoperative ulnar nerve dysfunction is not well studied. Our purpose was to determine the incidence of ulnar nerve dysfunction after open reduction and internal fixation of distal humerus fractures and identify factors associated with its development. DESIGN: Retrospective cohort study from two university-based institutions. PATIENTS: The medical records of 69 patients with a minimum of 12 months follow-up (median, 15 months; range, 12-72 months) after open reduction and plate and screw fixation of a bicolumnar fracture of the distal humerus (Orthopaedic Trauma Association Types 13A and C) that did not have preoperative ulnar nerve dysfunction were reviewed retrospectively. INTERVENTION: Surgical repair of a distal humerus fracture with or without ulnar nerve transposition. MAIN OUTCOMES: Ulnar nerve function was graded immediately postoperatively and at final follow-up according to a modified system of McGowan. Those with and without ulnar neuropathy were analyzed for differences in final position of the nerve (anterior versus in the cubital tunnel), open injury, multiple procedures, ipsilateral injury, and demographic factors. RESULTS: : The incidence of immediately postoperative ulnar nerve dysfunction documented in the medical record was seven of 69 patients (10.1%) (McGowan grades: 1 [57%], 2 [43%], 3 [0%]). The incidence of ulnar nerve dysfunction at final follow-up was 16% (11 of 69 patients) (McGowan grades: 1 [72%], 2 [28%], 3 [0%]). No demographic, injury, or treatment factors were associated with a risk of postoperative ulnar nerve dysfunction. CONCLUSION: There is a substantial incidence of postoperative ulnar nerve dysfunction after open reduction and plate and screw fixation of the distal humerus, which is likely underestimated by this retrospective analysis. Prospective studies using careful preoperative nerve evaluation and systematic postoperative nerve assessment are likely to identify an even higher incident of postoperative ulnar nerve dysfunction. Transposition was not protective in this analysis. PMID- 20577069 TI - Clinical results for minimally invasive locked plating of proximal humerus fractures. AB - OBJECTIVES: To describe the minimally invasive treatment of fractures of the proximal humerus using the Non-Contact-Bridging (NCB) plate. The system allows secondary locking of screws to the plate with a locking cap and polyaxial (30 degrees radius) screw placement. DESIGN: Prospective cohort study. SETTING: University Level I trauma center. PATIENTS: Fifty-four patients with unstable fractures of the proximal humerus. INTERVENTION: Minimal anterolateral acromial approach to the proximal humerus, percutaneous fracture reduction, and minimally invasive application of the NCB plate. MAIN OUTCOME MEASUREMENTS: Constant Score and radiologic follow-up (anteroposterior and transscapular). Visual Analog Scale for subjective evaluation of pain and function. RESULTS: After 17 months, the average Constant Score was 66.8 points (87% of the age- and sex-related normal values). Implant-related complications (plate impingement, screw perforation into the glenohumeral joint, loosening of screws) occurred in nine cases (17%). The rate of avascular necrosis was low (5.5%) and no cases of nonunion were seen. CONCLUSIONS: The effectiveness of the NCB is similar to other published methods of treatment for fractures of the proximal humerus and potentially provides a less invasive option for this problem. Complication rates and functional outcome in this series are comparable to the literature. An important factor in this technique is the process of percutaneous fracture reduction. The NCB plate is suitable for both a minimally invasive technique or standard open reduction and internal fixation through a deltopectoral approach; the surgeon must decide which approach is best for each particular fracture pattern and should be comfortable with both techniques. PMID- 20577070 TI - Closed reduction and minimally invasive percutaneous fixation of proximal humerus fractures using the Humerusblock. AB - OBJECTIVE: To evaluate the results after closed reduction and percutaneous fixation of displaced fractures of the proximal humerus with the Humerusblock system. DESIGN: Prospective case series. SETTING: Level 1 trauma center. PATIENTS AND METHODS: Fifty-eight consecutive patients with displaced proximal humerus fractures were followed over a mean period of 15.2 (12-28) months. INTERVENTION: All patients were treated by closed reduction and percutaneous fixation using the Humerusblock. MAIN OUTCOME MEASUREMENTS: Intra- and postoperative complications, secondary fracture displacement, rate of avascular necrosis, range of motion, pain according to a visual analogue scale, and the Constant-Murley shoulder score. RESULTS: No intra-operative complications occurred. Implant removal was performed 6 to 8 weeks after the initial surgery. In 13 (22%) cases, secondary impaction of the humerus lead to perforation of k-wires through the articular surface requiring premature removal of the entire implant after an average time of 4.9 weeks. Five patients required revision surgery, including open reduction and fixation because of secondary fracture displacement. In five patients, k wires loosened and backed out laterally, requiring revision surgery and retightening of the clamping screws in three cases and premature implant removal in two. Two patients showed radiologic signs of partial avascular necrosis at the final follow-up. The average range of motion of the operated shoulder was flexion 119.2 degrees, extension 33.5 degrees, internal rotation 64.2 degrees, external rotation 41.4 degrees. and abduction 107 degrees. The mean visual analogue scale pain score was 1.1 points, and the mean Constant-Murley score was 73.6 points, representing 88% of the mean Constant-Murley score of the unaffected shoulder. CONCLUSION: The Humerusblock system allows reliable minimally invasive fixation of selected displaced proximal humerus fractures, even in elderly patients with potentially reduced bone mass. In this study, postoperative rates of avascular necrosis were lower than that which has been reported after conservative treatment and open anatomic reduction and internal fixation. The overall unplanned re-operation rate of 40% was high, comparable with what has been reported for conventional percutaneous pinning. However, clinical outcome was good in 77% of the patients, and reduction could be held in 91% successfully, including elderly patients with potentially reduced bone mass. PMID- 20577071 TI - Safety and efficacy of conversion from external fixation to plate fixation in humeral shaft fractures. AB - OBJECTIVE: Immediate external fixation and planned conversion to internal fixation of humeral shaft fractures is an option in the treatment of associated severe soft-tissue injuries and severely injured patients. The purpose of this study was to evaluate the outcome and complications of patients who sustained humeral shaft fractures and were treated with initial unilateral external fixation followed by plate fixation. DESIGN: Retrospective analysis of a prospective database. SETTING: Academic level I trauma center. PATIENT/PARTICIPANTS: We identified 17 patients treated between June 2003 and August 2007 with immediate unilateral external fixation followed by planned conversion to internal plate fixation. All patients were seen for follow-up until bony union occurred, with a minimum follow-up of 6 months. MAIN OUTCOME MEASUREMENTS: Initial patient condition, local and systemic complications, and short-term outcomes were evaluated. RESULTS: The main reason for immediate placement of an external fixator was multiple trauma in nine patients (damage control orthopedics group); six open fractures with massive soft-tissue injury; one temporarily decreased perfusion to the forearm and hand; and one associated compartment syndrome of the upper arm. The average timing of the conversion to internal fixation was 6.2 (range, 2-14) days from the time of external fixation. There were no iatrogenic nerve injuries after either the external fixation or the conversion to internal fixation. Fifteen of 17 fractures united with an average time to healing of 11.1 (range, 8-14) weeks. Two fractures failed to heal after conversion from external to internal fixation. Both were open fractures from the non-damage control orthopedics group that developed a deep infection. There were no systemic complications after conversion from external to internal fixation. CONCLUSIONS: Immediate external fixation with planned conversion to plate fixation within 2 weeks proved to be a safe and effective approach for the management of humeral shaft fractures in selected patients with multiple injuries or severe soft-tissue injuries that preclude early plate fixation. PMID- 20577072 TI - Superior versus anteroinferior plating of the clavicle revisited: a mechanical study. AB - OBJECTIVES: This study was designed to compare bone-implant stiffness of two fixation techniques on a sawbone model of a clavicle fracture. METHODS: Twenty four preosteotomized synthetic left clavicles (Sawbones Worldwide, Vashon, WA) were divided into four groups based on type of fixation: standard 3.5-mm pelvic reconstruction plate in the superior position; standard 3.5-mm pelvic reconstruction plate in an anteroinferior position; 3.5-mm locking pelvic reconstruction plate in a superior position; and a 3.5-mm locking pelvic reconstruction plate in an anteroinferior position. Three nondestructive cyclic mechanical tests were performed in random order: axial, torsion, and four-point bend. RESULTS: No significant difference was found in axial (P = 0.61) or torsional stiffness (internal rotation, P = 0.46 or external rotation, P = 0.49) among all groups. No significant difference occurred in bending rigidity (four point bending test) with type of plate (P = 0.41), but when the plate was placed anteroinferiorly, bending rigidity was significantly higher (P < 0.001) than in the superior position. CONCLUSION: Placing the plate anteroinferiorly on the clavicle provides a more stable construct in terms of bending rigidity with no detriment in axial and torsional stiffness compared with placing the plate superiorly. We believe that anteroinferior plating is preferred as a result of the increase in bending rigidity together with other advantages, including avoidance of neurovascular compromise, the use of longer screws, and decreased hardware prominence. PMID- 20577073 TI - Is surgery for displaced, midshaft clavicle fractures in adults cost-effective? Results based on a multicenter randomized, controlled trial. AB - OBJECTIVES: To determine the cost-effectiveness of open reduction internal fixation (ORIF) of displaced, midshaft clavicle fractures in adults. DESIGN: Formal cost-effectiveness analysis based on a prospective, randomized, controlled trial. SETTING: Eight hospitals in Canada (seven university-affiliated and one community hospital). PATIENTS/PARTICIPANTS: One hundred thirty-two adults with acute, completely displaced, midshaft clavicle fractures. INTERVENTION: Clavicle ORIF versus nonoperative treatment. MAIN OUTCOME MEASUREMENTS: Utilities derived from SF-6D. RESULTS: The base case cost per quality-adjusted life-year (QALY) gained for ORIF was $65,000. Cost-effectiveness improved to $28,150/QALY gained when the functional benefit from ORIF was assumed to be permanent with cost per QALY gained falling below $50,000 when the functional advantage persisted for 9.3 years or more. In other sensitivity analyses, the cost per QALY gained for ORIF fell below $50,000 when ORIF cost less than $10,465 (base case cost $13,668) or the long-term utility difference between nonoperative treatment and ORIF was greater than 0.034 (base case difference 0.014). Short-term disutility associated with fracture healing also affected cost-effectiveness with the cost per QALY gained for ORIF falling below $50,000 when the utility of a fracture treated nonoperatively before union was less than 0.617 (base case utility 0.706) or when nonoperative treatment increased the time to union by 20 weeks (base case difference 12 weeks). CONCLUSIONS: The cost-effectiveness of ORIF after acute clavicle fracture depended on the durability of functional advantage for ORIF compared with nonoperative treatment. When functional benefits persisted for more than 9 years, ORIF had a favorable value compared with many accepted health interventions. PMID- 20577074 TI - Closed reduction and internal fixation of completely displaced and rotated lateral condyle fractures of the humerus in children. AB - OBJECTIVE: To determine the usefulness of closed reduction and internal fixation as the initial treatment for completely displaced and rotated fractures of the lateral condyle of the humerus in children. DESIGN: Prospective. SETTING: Three Level I trauma centers. PATIENTS: We prospectively studied 24 consecutive completely displaced and rotated lateral condylar fractures of the humerus in children (Jakob Stage 3, 20 boys and four girls) that were treated by three different surgeons working at different hospitals during the same period. INTERVENTION: In 21 fractures, we initially attempted closed reduction and internal fixation; in three, we used open reduction and internal fixation and made no attempt at closed reduction. MAIN OUTCOME MEASUREMENT: We assessed the preoperative degree of displacement and postoperative radiographic quality of closed reduction. Clinical results were graded using the criteria suggested by Hardacre et al. RESULTS: Eighteen of 24 (75%) completely displaced and rotated fractures were reduced within 2 mm of residual displacement using the closed method. Three fractures were treated with open reduction and internal fixation initially and internal fixation because of one surgeon's lack of confidence in closed reduction, because of lack of experience with it, early in the study period. Closed reduction to within 2 mm failed in three fractures, so open reduction and internal fixation was then performed. There were no significant complications such as limited range of motion, pain, osteonecrosis of the trochlea or capitellum, nonunion, malunion, or early physeal arrest. CONCLUSION: Closed reduction and internal fixation is an effective treatment for completely displaced and rotated lateral condyle fractures of the humerus in many children. PMID- 20577075 TI - Fractures of the lateral humeral condyle are the second most frequent elbow fracture in children. PMID- 20577076 TI - The treatment of displaced fractures of the lateral humeral condyle in children. PMID- 20577077 TI - Stabilization of adolescent both-bone forearm fractures: a comparison of intramedullary nailing versus open reduction and internal fixation. AB - OBJECTIVES: To compare flexible intramedullary (IM) nailing with open reduction and internal fixation (ORIF) with plates and screws in the treatment of adolescent both-bone forearm fractures. DESIGN: Retrospective comparative study. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Sixty-one skeletally immature adolescents (mean age, 13.9 years; range, 11.5-16.9 years) treated operatively for both-bone forearm fractures from 1997 to 2007. Patients with Monteggia, Galeazzi, intra-articular, and pathologic fractures were excluded. INTERVENTION: Forty-six patients (mean age, 14.1 years) underwent ORIF and 15 patients (mean age, 13.3 years) underwent flexible IM nailing. MAIN OUTCOME MEASURES: Time to fracture union, forearm rotation, magnitude and location of maximal radial bow, and complications. RESULTS: There was no difference in mean time to union between the IM nailing (8.5 weeks) and ORIF (8.9 weeks) groups, although the study did not have sufficient power to detect a difference. Eighty three percent of patients in both groups regained full forearm rotation. Although radial bow magnitude was comparably restored in both groups, the mean location of maximal radial bow was translated distally in the IM nailing group (67.2%) compared with the ORIF group (60.1%, P < 0.001) and a previously reported normal value (60.4%, P < 0.001). There were no major complications in the IM nailing group and five major complications in the ORIF group. CONCLUSIONS: Flexible IM nailing of both-bone form fractures in adolescents was safe and effective in our small series; we had less complications when compared with conventional ORIF. Although flexible IM nailing results in distal translation of the radial bow, forearm rotation is not compromised. PMID- 20577078 TI - Validity of conventional radiography in determining scaphoid waist fracture displacement. AB - OBJECTIVE: This study examines interpreter accuracy and interobserver agreement in evaluating conventional radiographs for scaphoid waist fracture displacement. METHODS: Six fresh-frozen cadaver arms were obtained transected above the elbow. A waist fracture was created in each scaphoid. In a random fashion, three of the fractures were displaced 1 mm in the radial-ulnar plane, whereas the other three were reapproximated to anatomic position before all fractures were stabilized with radiolucent adhesive glue. A three-view conventional radiography series consisting of a posterior-anterior, lateral, and ulnar-deviated elongated scaphoid view was obtained for each wrist. Each radiograph was then presented in the same sequence for interpretation to six independent observers: two hand surgeons, two musculoskeletal radiologists, and two senior orthopaedic surgery residents who were all blinded to the actual fracture pattern. RESULTS: In 14 of the 18 (78%) displaced fracture radiographic series, the interpreters correctly recognized displacement being present. However, displacement was also reported in six of the 18 (33%) nondisplaced fracture series. The estimated overall accuracy of all readings for distinguishing between displaced and nondisplaced fractures was 72%. Of the 90 total possible pairwise agreements between interpreters regarding fracture displacement, there were 54 actual agreements (60%), and kappa was estimated to be 0.31. Taken together, these two measures of agreement can be interpreted as indicating poor to moderate agreement. CONCLUSION: Our results suggest that conventional radiography is not reliable in determining 1-mm scaphoid waist fracture displacement in the radioulnar plane and also indicated a lack of strong interobserver agreement. PMID- 20577079 TI - A novel field-of-view augmentation wand for C-arm computed tomography-like fluoroscopy-based intraoperative navigation new technology. AB - Intraoperative fluoroscopically based computed tomography, integrated with a navigation system, holds great potential for improving visualization and navigation in orthopedic procedures. However, a limited field of view generated by the fluoroscopically based computed tomography has imposed a serious limitation, especially for navigation-based procedures. The device presented in this article enables one to overcome the limitation of the small field of view. The device has been evaluated in vitro by five physicians and has been used successfully in one clinical case. In general, we have developed a simple, low cost in-house device that helps overcome an intrinsic limitation of high-cost systems. PMID- 20577080 TI - Promontory sign in a reactive benign vascular proliferation. AB - The promontory sign was described 27 years ago and it was claimed to be useful in the diagnosis of early stages of Kaposi sarcoma. However, it is not pathognomonic, because it has also been described in angiosarcoma and in benign vascular tumors. Some authors claim that some reactive vascular lesions known as pseudo-Kaposi do not present the promontory sign. We report the case of a vascular cutaneous lesion on the breast of a 75-year-old woman, which had a benign clinical behavior, and presented with the promontory sign. The lesion was made of tortuous dilated lymphatic tissue, and small capillaries with a lobular distribution. It was characterized by CD31 and D240 immunostaining, although no immunostaining for human herpesvirus 8 (HHV8) was found. The lesion spontaneously improved and eventually disappeared. It was thought to be secondary to a chronic trauma to the area due to a prolonged stance in bed in the emergency room. PMID- 20577081 TI - Effective ionic dialysance/blood flow rate ratio: an indicator of access recirculation in arteriovenous fistulae. AB - Effective ionic dialysance (EID) is an online measure of hemodialysis (HD) effective urea clearance that is calculated using changes in dialysate sodium conductivity. Effective ionic dialysance is blood flow (Q(b)) dependent. The presence of significant (> or =5%) access recirculation (sAR) during dialysis lowers EID at a given Q(b), thereby lowering EID/Q(b). We propose using EID/Q(b) as a useful chairside tool for detection of sAR in arteriovenous fistulae (AVF). Data were collected from 47 patients with AVF (72% men, mean age 49 +/- 11.8 years, duration on dialysis 3.78 +/- 3.4 years, duration of fistula use 3.35 +/- 3.42 years) dialyzed with an high-efficiency dialyzer with a mass transfer area coefficient (KoA) of 1714 ml/min. Effective ionic dialysance were measured at regular intervals by the Gambro Phoenix dialysis system during treatments. The access recirculation (AR) and access blood flow (Q(a)) were measured using the reference standard saline dilution technique (Transonic HD-02 monitor). Among the 323 HD sessions where Q(b), EID, AR, and Q(a) were available, we identified 17 instances of sAR. The performance of EID/Q(b) as indicator of sAR was assessed by a receiver operator characteristic (ROC) curve (Stata version 10.1). The area under the ROC curve was 0.935 (95% confidence interval 0.869-1.000), which demonstrated a sensitivity of 76.5% and specificity of 96.4% at an EID/Q(b) < or =50% with a positive likelihood ratio of 21, negative likelihood ratio of 0.24, positive predictive value of 54.2%, and negative predictive value of 98.7%. We found similar test performance in patients who received HD with dialyzers with smaller surface areas and lower KoAs. The high specificity of EID/Q(b) makes it an excellent yet simple and early chairside indicator of AVF recirculation. PMID- 20577083 TI - A family with hereditary congenital facial paresis and a brief review of the literature. AB - Hereditary congenital facial paresis is a rare syndrome of isolated facial nerve palsy causing facial asymmetry and ptosis. Most described cases follow an autosomal dominant pattern of inheritance. It differs from Moebius syndrome, which is usually sporadic and associated with the involvement of other cranial nerves, commonly the abducens nerve in addition to orofacial and limb malformations and defects of the musculoskeletal system. We present three patients from the same family with features of congenital hereditary facial paresis. Facial asymmetry and facial weakness were the most remarkable findings. High-resolution imaging showed both facial nerves to be present but symmetrically and markedly hypoplastic with no other structural abnormality in the brainstem. This syndrome has been previously mapped to chromosome 3q21-22 but no gene has been identified as yet. PMID- 20577082 TI - Different patterns of peripheral versus central blood pressure in hypertensive patients treated with beta-blockers either with or without vasodilator properties or with angiotensin receptor blockers. AB - BACKGROUND: It is unclear whether the assumed inferiority of atenolol to reduce central (aortic) blood pressure (BP) extends to other beta-blockers with vasodilating properties and, within that scope, how these drugs differ from the angiotensin receptor blockers (ARBs). METHODS: In a retrospective study, we compared three groups of hypertensive patients (aged 35-65 years) chronically treated with either ARBs (n=83, group 1), carvedilol/nebivolol (n=75, 25+25 mg/day/5 mg/day, group 2) or atenolol (n=84, 50-100 mg/day, group 3), matched for age (mean 52 years), sex (61% female), brachial BP and concomitant use of diuretics (75-81%)and dihydropyridine calcium antagonists (27-33%). We measured aortic stiffness by pulse wave velocity (Complior), and central BP, central peripheral pulse pressure amplification, wave reflection [augmentation index (AIx) corrected for heart rate] and augmentation pressure (Sphygmocor). RESULTS: For similar age, sex distribution, brachial BP levels (145/85+/-11/10 mmHg) and pulse wave velocity (10+/-2 m/s), the atenolol group showed significantly (P<0.03 analysis of variance) higher central systolic BP (139+/-9 mmHg) versus group 2 (135+/-10 mmHg) and group 1 (132+/-11 mmHg), higher AIx (34+/-12%) versus group 2 (27+/-7%) and group 1 (23.0+/-9%), lower pulse pressure amplification (1.16+/ 0.09) versus group 2 (1.22+/-0.10) and group 1 (1.31+/-0.11) and lower heart rate beats/min (61+/-9) versus group 2 (69+/-11) and group 1 (82+/-11). The differences on these values, between group 2 and group 1, were also significant (P<0.04). After adjustment for the heart rate, AIx became similar in groups 2 and 1, but still lower (P<0.04) than the atenolol group. CONCLUSION: These findings suggest that, for similar brachial BP and aortic stiffness, treatment with either vasodilating beta-blockers or angiotensin receptor blockers associates with lower central systolic BP and wave reflections than treatment with atenolol. These findings may suggest that the vasodilating beta-blockers may exert more favourable central haemodynamic effects, compared with atenolol, which are more alike, although not completely equal, to those of the ARBs. PMID- 20577084 TI - Corneal crosslinking and visual rehabilitation in keratoconus in one session without epithelial debridement: new technique. AB - A new surgical technique for the treatment of keratoconus is presented. This technique combines a new corneal crosslinking method with implantation of a flexible full-ring implant into a "closed" corneal pocket via a narrow incision tunnel in 1 surgical session. Riboflavin is not applied in the form of eyedrops onto a corneal surface after epithelial removal but is instilled into the corneal pocket without the need for epithelial debridement. A case of advanced keratoconus treated in this manner is presented. Uncorrected visual acuity increased by 7 lines from 0.05 to 0.25, and the average central K reading decreased by 11 diopters. The haze seen during the early postoperative period diminished in the first month after surgery. PMID- 20577085 TI - Sjogren syndrome and dry eye: the impact of corneal refractive surgery. PMID- 20577087 TI - Distinct dacryoadenitides autoadoptively transferred to rabbits by different subpopulations of lymphocytes activated ex vivo. AB - PURPOSE: To test whether CD4+ T cells proliferate in mixed cell reactions with autologous lacrimal gland (LG) acinar cells and whether these cells can autoadoptively transfer disease. METHODS: Purified acinar cells were gamma irradiated and cocultured with peripheral blood lymphocytes. Activated CD4+ T cells were sorted by fluorescence-activated cell sorting (FACS). Unfractionated activated peripheral blood lymphocytes (UF), CD4+-enriched and CD4+-depleted T cells from an autologous mixed cell reaction were injected into the donor rabbit's remaining LG. After 4 weeks, ocular examinations were performed, and the rabbits were euthanized; LGs were removed for histopathology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction studies. RESULTS: CD4 T cells increased in the autologous mixed cell reaction from 20% to 80%. Tear production decreased in the induced disease/UF (ID/UF) group and declined even more in the ID/CD4+-enriched group. Tear breakup times decreased and rose bengal staining increased in all groups. All LGs exhibited significant histopathology and increased messenger RNAs for tumor necrosis factor alpha. The ID/UF group exhibited the largest increases of CD4+ and rabbit T-lymphocyte antigen-positive cells. The ID/CD4+-enriched group contained fewer infiltrating CD4 cells but more eosinophils, severely altered acinar morphology, and increased fibrosis. LG of the ID/CD4+-depleted group exhibited large increases of CD18, major histocompatibility complex II, and CD4+ cells. Messenger RNAs for interleukin 2, interleukin 4, and CD4+ increased in the ID/CD4+-enriched group compared with the CD4+-depleted group. CONCLUSIONS: Autoreactive CD4+ effector cells activated ex vivo and autoadoptively transferred, caused what seems to be a distinct dacryoadenitis. The CD4+-depleted cell fraction also contained pathogenic effector cells capable of inducing disease. PMID- 20577088 TI - Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques. AB - PURPOSE: Tear hyperosmolarity is diagnostic of dry eye disease (DED), yet difficulty in measurement has limited its utility; development of new instruments could facilitate its clinical application. This study compares the new OcuSense TearLab osmometer (OcuSense, Inc, San Diego, CA), based on electrical impedance "lab-on-a-chip" nanoliter technology, with the freezing point depression Clifton Osmometer (Clifton Technical Physics, Hartford, NY). METHODS: Thirty-six subjects were recruited: 15 DED (9 women, 6 men age: 41 +/- 16 years) and 21 controls (12 women, 9 men age: 35 +/- 12 years); criteria for DED were noninvasive tear breakup time <10 seconds, Schirmer I test <5 mm, and positive symptoms. Samples were collected from the inferior tear meniscus for testing with both osmometers. RESULTS: Osmolarity values measured with OcuSense TearLab were 308 +/- 6 and 321 +/- 16 mOsm/L for controls and dry eye, respectively, and those measured with Clifton were 310 +/- 7 and 323 +/- 14 mOsm/L for controls and dry eye, respectively; these values were significantly different. Significant correlation was found between OcuSense and Clifton measurements (r = 0.904; P = 0.006). Bland Altman analysis revealed agreement between techniques; the majority of points fell within the 95% confidence limits, and actual values differed by less than 1%. A cutoff value of >316 mOsm/L, derived from the distribution of osmolarity values, was used to diagnose DED with an effectiveness of 73% sensitivity, 90% specificity, and 85% positive predictive value for the OcuSense and 73% sensitivity, 71% specificity, and 65% positive predictive value for the Clifton in the study samples. CONCLUSIONS: Tear film osmolarity measured with the OcuSense TearLab system correlates well with the Clifton Osmometer. The new instrument has the potential to provide clinicians with a readily available clinically applicable measure, which could become the gold standard in DED. PMID- 20577090 TI - IL-8 decreases HIV-1 transcription in peripheral blood lymphocytes and ectocervical tissue explants. AB - IL-8 is enhanced in the peripheral blood and lymphoid tissue of HIV-infected individuals, suggesting that IL-8 is important in the pathogenesis of HIV-1 infection and progression to AIDS. Characterizing the mechanisms of IL-8 regulation of HIV-1 replication may be relevant in addressing the role of IL-8 as a therapeutic target in HIV-1 infection. We evaluated replication of primary R5 tropic HIV-1 in peripheral blood lymphocytes and ectocervical tissue explants infected in vitro in the presence of physiological concentrations of IL-8 found in the serum and genital tract secretions of HIV-infected individuals. To identify the specific stages of the viral life cycle targeted by IL-8, we performed real-time polymerase chain reaction to detect HIV-1 reverse transcription, integration, and transcription. Early during the infection, IL-8 decreased HIV-1 reverse transcription and viral integration. This effect was transient, as on day 4 after infection, we detected no differences on HIV-1 DNA or proviral DNA in peripheral blood lymphocyte. IL-8 decreased HIV-1 transcription in both lymphocytes and ectocervical tissue explants. The decrease in viral RNA expression was associated with reduced HIV-1 replication, as measured by viral p24 release in the culture supernatants. This is the first report to suggest that IL-8 decreases replication of primary R5-tropic HIV-1 by transcriptional mechanisms. PMID- 20577091 TI - Insulin resistance impairs response to interferon plus ribavirin in patients coinfected with HIV and hepatitis C virus. AB - BACKGROUND/AIMS: Controversy exists about whether insulin resistance (IR) affects response to treatment of hepatitis C. We evaluated the effect of IR on sustained virologic response (SVR) in HIV/hepatitis C virus (HCV)-coinfected patients treated with interferon plus ribavirin. METHODS: We reviewed the clinical records of HIV/HCV-coinfected patients who received interferon plus ribavirin at our institution between July 2000 and March 2007. IR was defined as a homeostasis model assessment >= 3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after the end of treatment. Efficacy was evaluated using an on-treatment (OT) analysis. Multivariate logistic regression analysis was used to evaluate factors associated with SVR. RESULTS: During the study period, 218 patients were treated with interferon plus ribavirin; IR at baseline was available for 162 patients, and 134 were included in the OT analysis; HCV genotype (G) 1/4, 67%; F3-F4 fibrosis, 36%; IR 31%. SVR was achieved in 67 patients (50%) (79% in G 2/3 vs. 38% in G 1/4). IR was associated with a lower SVR [odds ratio (OR), 0.33; 95% confidence interval (CI): 0.15-0.72; P = 0.006). The independent variables related to SVR were genotype 2/3 (OR, 6.7; 95% CI: 2.71-16.98; P < 0.001), absence of IR at baseline (OR, 3.3; 95% CI: 1.36-8.26; P = 0.008), and nadir CD4 T-cell count (OR, 1.002; 95% CI: 1.00-1.00; P = 0.047). CONCLUSIONS: Our data suggest that IR is an important determinant of SVR in HIV/HCV-coinfected patients treated with interferon plus ribavirin. Strategies to modify IR should be explored to enhance SVR during anti-HCV therapy. PMID- 20577093 TI - Avascular necrosis of the metacarpals in juvenile dermatomyositis. AB - Avascular necrosis (AVN) of the metacarpal heads is uncommon and has been associated with trauma, systemic lupus erythematosus, and corticosteroid usage. There have been no previous reports of metacarpal AVN described in patients with juvenile dermatomyositis. Descriptions of AVN in juvenile dermatomyositis are rare. We present 2 cases of patients with juvenile dermatomyositis who developed multifocal avascular necrosis after corticosteroid therapy with unusual distribution and review the literature on metacarpal AVN. PMID- 20577094 TI - Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab. AB - Stiff-person syndrome is a rare neurologic disorder characterized by fluctuating and progressive stiffness of axial and limb musculature. The high prevalence of autoantibodies and associated autoimmune diseases in patients with stiff person syndrome suggests that it may have an autoimmune etiology. We report a case of a 62-year-old man with diabetes who developed progressive stiffness of the hips and legs and elevated levels of antibody to glutamic acid decarboxylase. He had a partial response to both baclofen and diazepam, but could not tolerate the treatment because of somnolence. He eventually received 2 infusions of rituximab 1000 mg a week apart. The baclofen was discontinued and the diazepam was tapered. However, 6 months after the rituximab treatment, despite continued clinical improvement the patient had persistently elevated titers of antibody to glutamic acid decarboxylase. We postulate that rituximab was associated with clinical improvement through mechanisms other than antibody depletion. PMID- 20577092 TI - Genetic variation of innate immune genes in HIV-infected african patients with or without oropharyngeal candidiasis. AB - BACKGROUND: The occurrence of oropharyngeal candidiasis (OPC) in combination with HIV disease progression is a very common phenomenon. However, not all HIV infected patients develop OPC, even when they progress to low CD4 T-cell counts. Because T-cell immunity is defective in AIDS, the innate defence mechanisms are likely to have a central role in antifungal immunity in these patients. We investigated whether genetic variations in the innate immune genes DECTIN-1, TLR2, TLR4, TIRAP, and CASPASE-12 are associated with the presence of OPC in HIV infected subjects from East Africa. METHODS: A total of 225 HIV patients were genotyped for several single nucleotide polymorphisms (SNPs), and this was correlated with the occurrence of OPC in these patients. In addition, primary immune cells obtained from individuals with different genotypes were stimulated with Candida albicans, and cytokine production was measured. RESULTS: The analysis revealed that no significant differences in the polymorphism frequencies could be observed, although a tendency toward a protective effect on OPC of the DECTIN-1 I223S SNP was apparent. Furthermore, interferon gamma production capacity was markedly lower in cells bearing the DECTIN-1 SNP I223S. It could also be demonstrated that the 223S mutated form of the DECTIN-1 gene exhibits a lower capacity to bind zymosan. CONCLUSIONS: These data demonstrate that common polymorphisms of TLR2, TLR4, TIRAP, and CASPASE-12 do not influence susceptibility to OPC in HIV-infected patients in East Africa but suggest an immunomodulatory effect of the I223S SNP on dectin-1 function and possibly the susceptibility to OPC in HIV patients. PMID- 20577089 TI - EUROASPIRE III. Management of cardiovascular risk factors in asymptomatic high risk patients in general practice: cross-sectional survey in 12 European countries. AB - OBJECTIVE: To determine whether the 2003 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been followed in general practice. DESIGN: Cross-sectional survey. METHODS: The EUROASPIRE survey was carried out in 2006-2007 in 66 general practices in 12 European countries. Patients without a history of coronary or other atherosclerotic disease either started on antihypertensive and/or lipid-lowering and/or antidiabetes treatments were identified retrospectively, interviewed and examined at least 6 months after the start of medication. RESULTS: Four thousand, three hundred and sixty-six high-risk individuals (57.7% females) were interviewed (participation rate 76.7%). Overall, 16.9% smoked cigarettes, 43.5% had body mass index >=30 kg/m, 70.8% had blood pressure >=140/90 mmHg (>=130/80 in people with diabetes mellitus), 66.4% had total cholesterol >=5.0 mmol/l (>=4.5 mmol/l in people with diabetes) and 30.2% reported a history of diabetes. The risk factor control was very poor, with only 26.3% of patients using antihypertensive medication achieving the blood pressure goal, 30.6% of patients on lipid-lowering medication achieving the total cholesterol goal and 39.9% of patients with self-reported diabetes having haemoglobin A1c <=6.1%. The use of blood pressure-lowering medication in people with hypertension was: beta-blockers 34.1%, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 60.8%, calcium channel blockers 26.3%, diuretics 36.9%. Statins were prescribed in 47.0% of people with hypercholesterolemia. About 22.0% of all patients were on aspirin or other antiplatelet medication. CONCLUSION: The EUROASPIRE III survey in general practice shows that the lifestyle of people being treated as high cardiovascular risk is a major cause of concern with persistent smoking and high prevalence of both obesity and central obesity. Blood pressure, lipid and glucose control are completely inadequate with most patients not achieving the targets defined in the prevention guidelines. Primary prevention needs a systematic, comprehensive, multidisciplinary approach, which addresses lifestyle and risk factor management by general practitioners, nurses and other allied health professionals, and a health care system which invests in prevention. PMID- 20577095 TI - Factors associated with disability in patients with rheumatoid arthritis. AB - OBJECTIVE: Analyze disability determinants in a cohort of Argentine patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Consecutive patients with RA, according to ACR'87 criteria, were recruited from 6 rheumatology centers. Demographic and socioeconomic data, family history, comorbid diseases, extra articular manifestations and information about received treatments were provided. Disease activity was assessed using Disease Activity Score 28 (DAS 28) and the Health Assessment Questionnaire (HAQ)-A was used for the functional capacity. Hand and feet radiographs were assessed using Sharp-van der Heijde score. RESULTS: A total of 640 patients with RA were included, of which 85.2% were females. Mean age was 53 years (interquartile range [IQR], 44-62) and mean disease duration was 8 years (IQR, 4-14). DAS 28 mean was 2.72 (IQR, 1.7-3.7) and HAQ-A mean was 0.62 (IQR, 0.13-1.25). Multiple linear regression showed that the main variables associated with disability were DAS 28, radiologic damage and age. Main predictors of functional disability in the multiple logistic regression using severe HAQ (>2) as dependent variable were DAS 28 (OR, 2; P < 0.0001); age (OR, 1; P = 0.008); and structural damage (OR, 1; P = 0.001). CONCLUSIONS: In this population, the disease activity was the variable that showed the highest impact on the physical function. Radiologic damage affected HAQ as the disease progressed. PMID- 20577096 TI - GDx staging system: a new method for retinal nerve fiber layer damage classification. AB - PURPOSE: To provide a reliable and easy-to-use method for classifying retinal nerve fiber layer (RNFL) damage using the parameters obtained by the scanning laser polarimeter with variable corneal compensator (GDx VCC). METHODS: GDx Staging System is a new method that uses the superior and inferior RNFL thickness values plotted on an x-y diagram to classify GDx VCC results. RNFL defects are classified into 6 stages of increasing severity and 3 classes of defect localization (superior, inferior, or diffuse defect). The diagram was created based on 320 GDx VCC tests from 84 healthy controls and from 236 patients affected by ocular hypertension or chronic open-angle glaucoma. Sensitivity and specificity of the method were assessed in a different cohort that included 161 patients with either ocular hypertension or open-angle glaucoma, and 34 normal participants. The results were correlated with both a clinical classification of the GDx VCC results and with visual field defects classified with the Glaucoma Staging System 2. RESULTS: Sensitivity and specificity of the GDx Staging System were, respectively, 88.2% and 100%. Correlations with the clinical classification and the Glaucoma Staging System 2 results were statistically significant (Spearman correlation coefficient 0.92 and 0.57, respectively; P<0.0001). CONCLUSIONS: The GDx Staging System is an easy and quick method for interpreting GDx VCC results. It can be clinically useful, especially for nonexpert ophthalmologists. PMID- 20577097 TI - Goldmann applanation tonometry and dynamic contour tonometry are not correlated with central corneal thickness in primary open angle glaucoma. AB - PURPOSE: To compare intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) and assess their relationship to central corneal thickness (CCT) in patients with primary open angle glaucoma (OAG). PATIENTS AND METHODS: GAT, DCT, and CCT were assessed in 116 patients with OAG [mean age 65.9 (10.5); 59% female] participating in the Indianapolis Glaucoma Progression Study. GAT and DCT were measured in a randomized order followed by CCT (ultrasonic corneal pachymetry) during a single study visit. Bland-Altman plots were used to evaluate the limits of agreement between tonometery methodologies whereas multivariate regression analysis was used to evaluate the influence of CCT on GAT and DCT IOP measurements. RESULTS: IOP values obtained by DCT and GAT showed a strong positive correlation in patients with OAG (r=0.93; P<0.001). Mean IOP measured with DCT [18.4 (5.1) mm Hg] was significantly higher (P<0.001) than GAT IOP measurements [16.5 (4.5) mmHg]. CCT did not seem to influence either GAT or DCT measurements (r=0.1025, P=0.16; r=0.05, P=0.46), respectively. The Bland-Altman data showed that the amount of disagreement between IOP assessment techniques varied, suggesting a proportional bias. CONCLUSIONS: In this group of patients with OAG, there was a strong correlation between GAT and DCT measurements of IOP. IOP measured with DCT was consistently higher than IOP measured with GAT. Neither GAT nor DCT measurements were correlated with CCT. This data suggests that factors other than CCT may be involved in the tendency of DCT to produce higher measures of IOP than GAT. PMID- 20577098 TI - The relationship between diabetes mellitus and exfoliation syndrome in a United States Veterans Affairs population: a case-control study. AB - PURPOSE: Earlier studies suggest that an inverse relationship exists between diabetes mellitus and exfoliation syndrome (ES). We evaluated the relationship between diabetes mellitus and ES while controlling for important covariates. In addition, we investigated whether glucose control, as measured by glycosylated hemoglobin (HbA1c) levels, differed between the subset of diabetic patients with and without ES. PATIENTS AND METHODS: This retrospective case-control study included outpatients seen in Veterans Affairs Boston Healthcare System eye clinics. Exfoliation cases (n=328) and controls (n=328) were drawn from the same clinic and matched for age. For all participants, we ascertained diabetes status, sex, race, body mass index, and glaucoma status. Among patients with diabetes mellitus, we collected the 5 most recent HbA1c levels and type of diabetes control. RESULTS: Diabetes mellitus was present in 96 (29.2%) cases and in 114 (34.8%) controls. In multivariate analysis, no statistically significant relationship between diabetes mellitus and ES (OR=0.77; 95% CI, 0.55-1.07) was identified. When glaucoma status was added as a covariate, the results were essentially unchanged (OR=0.81, 95% CI, 0.57-1.14). Adjusted mean HbA1c levels were similar in diabetic patients with (6.85%; 95% CI, 6.66-7.04) and without (7.05%; 95% CI, 6.87-7.22) ES (P=0.14). CONCLUSION: In this predominately white male population, we did not observe a statistically significant relationship between diabetes mellitus and ES. In addition, HbA1c levels did not vary among diabetic patient based on exfoliation status. PMID- 20577099 TI - The use of HRT with and without the aid of disc photographs. AB - PURPOSE: To evaluate the measurement of optic disc morphology using Heidelberg Retinal Tomography (HRT) with and without the aid of optic disc photos. METHODS: One hundred three children (aged 11 and 12 y, 52 boys) were selected randomly from the Singapore Cohort study of Risk Factors for Myopia. Optic nerve head topography and retinal nerve fiber layer thickness measurements were assessed using the HRT-II (Heidelberg, Germany) scanning laser ophthalmoscope. All contour lines were drawn by the same researcher on 2 occasions. The first drawing was made without optic disc photographs but using the 3-dimensional rotation assessment. The second drawing was made with the additional aid of digital monoscopic optic disc photographs. RESULTS: There was a high correlation between the measurements taken with and without optic disc photographs. For the global disc area, the difference between the mean readings was 0.67 mm and the intraclass correlation (ICC) was 0.81 [95% confidence interval (CI) 0.73-0.86]. The mean difference for the global cup-to-disc ratio was 0.03 [ICC 0.86 (95% CI 0.80-0.90)]. The ICCs were high across almost all of the readings except rim volume, in which the ICC was 0.57 (95% CI 0.43-0.69). CONCLUSIONS: This study shows minimal differences in HRT measured optic disc parameters when optic disc photos are used to aid in the definition of the scleral ring. Omitting the use of disc photographs in measuring HRT outputs may translate into significant savings in time and logistics in simultaneously obtaining HRT and optic disc photographs in large population-based studies. PMID- 20577100 TI - Sterile single use cover for the G-probe Transscleral Cyclodiode. AB - PURPOSE: Multiuse of the G-probe transscleral cyclophotocoagulation (TSCPC) device can lead to contamination. We evaluated the mechanical stability and clinical efficacy of a disposable sterile barrier for the G-probe footplate. METHODS: We measured diode laser output with and without the G-probe barrier both before and after cadaver TSCPC (18 shots at 2000 mW for 2000mS). Qualitative analyses of the laser aiming beam were made before each trial in the barrier and nonbarrier state. After each trial, the G-probe barrier was examined for microperforations and footplate for debris and/or damage. Microbiology was taken on the cadaver eye and the G-probe before and after 20 cycles. Histologic analysis after TSCPC with and without barrier was carried out on a cadaver eye. RESULTS: Qualitatively, laser focus dispersion was minimized by the G-probe cover. Mean (95% CI) laser output was measured for the nonbarrier, with barrier pre-TSCPC and with barrier post-TSCPC, respectively as 980 mW (899,1061), 1247 mW (1115, 1378), and 1240 mW (1132, 1347). The difference between the nonbarrier and barrier both preTSCPC and postTSCPC was statistically significant (df=2, F=36.26, P<0.01). No perforations in the G-probe barrier were evident and no debris or damage was detected on the G-probe. Pathology was consistent with earlier reports of TSCPC in cadaver eyes. Microbial segregation of the cadaver eye and the G probe footplate was maintained. CONCLUSIONS: The G-probe barrier is an effective and robust method to protect consecutive patients from contamination during TSCPC. Although energy levels were slightly higher in probes with barrier, histologic differences were not evident and the clinical significance of this finding is likely limited. PMID- 20577101 TI - Split-thickness hinged scleral flap in the management of exposed tubing of a glaucoma drainage device. AB - A split-thickness hinged scleral flap technique was devised to aid in tube exposure after glaucoma drainage device implantation. This technique resulted in the successful recovery of the tube without reexposure or serious complications in all 3 observed cases. Split-thickness hinged scleral flaps may be an effective surgical technique for the management of repeated tube exposure after glaucoma drainage device implantation. PMID- 20577102 TI - Rigidity of retinal vessel in untreated eyes of normal tension primary open-angle glaucoma patients. AB - BACKGROUND: To analyze pulse wave propagation in the ocular circulation and vessel stiffness in untreated eyes of normal tension primary open-angle glaucoma (NTG) patients. METHODS: Inferotemporal retinal vessels of 22 NTG eyes and 25 controls were examined with a Retinal Vessel Analyzer. Inferotemporal peripapillary retinal nerve fiber layer thickness was measured by ocular coherence tomography. Phase delay between venous trough and arterial peak was assessed at 3 sites centrifugal from the disc and a choroid-to-retina pulse delay was calculated as an estimation of vessel rigidity. RESULTS: There was choroid-to retina pulse delay of 0.26+/-0.08, 0.30+/-0.11, and 0.33+/-0.11 seconds, respectively, in NTG eyes at proximal, middle, and distal sites; in control eyes, the corresponding values were 0.28+/-0.10, 0.35+/-0.12, and 0.40+/-0.17 seconds. Average choroid-to-retina pulse delay was shorter in NTG eyes (P=0.028). Retinal nerve fiber layer (inferotemporal) showed an opposite correlation with choroid-to retina pulse delay in controls (r=-0.48, P=0.019) and in NTG eyes (r=0.47, P=0.032 ). CONCLUSIONS: Untreated NTG eyes show stiffer retinal vessels. Vessel rigidity correlates with level of glaucomatous damage. PMID- 20577103 TI - The effect of early posttrabeculectomy intraocular pressure spike in the collaborative initial glaucoma treatment study. AB - PURPOSE: To examine effects of early postoperative intraocular pressure (IOP) spike in patients undergoing primary trabeculectomy in the Collaborative Initial Glaucoma Treatment Study. PATIENTS AND METHODS: We identified patients with IOP spike >=5 mm Hg above the baseline IOP on postoperative day 1 and those without IOP increase. The mean deviation (MD), pattern standard deviation (PSD), and corrected PSD of the visual field (VF) were compared at 6 months and years 1, 2, 3, and 5 after surgery, as was the IOP. RESULTS: Seventeen of 300 patients (5.7%) had IOP spike. After controlling for baseline VF severity in a generalized linear regression model that addressed change in MD, PSD, and corrected PSD, or in a logistic regression model for >=3 dB of MD change, comparison between the groups revealed no significant difference at all time points examined (P>0.05). Patients with IOP spike had significantly higher mean IOP at years 3 and 5 of follow-up (P<=0.04). CONCLUSIONS: Among Collaborative Initial Glaucoma Treatment Study patients, early posttrabeculectomy IOP spike >=5 mm Hg above baseline IOP was not associated with subsequent VF loss, but was associated with significantly higher IOP during long-term follow-up. PMID- 20577104 TI - Central corneal thickness and anterior scleral thickness in Korean patients With Open-angle glaucoma: an anterior segment optical coherence tomography study. AB - PURPOSE: To assess the correlation between central corneal thickness (CCT) and anterior scleral thickness (AST) in Korean patients with normal tension glaucoma (NTG) and primary open angle glaucoma (POAG). PATIENTS AND METHODS: Consecutive patients with POAG, NTG, and normal individuals were recruited. Anterior segment optical coherence tomography (AS-OCT, Visante) was used to measure CCT and AST. The AST was measured 2 mm posterior to the scleral spur in the temporal meridian. Statistical analysis of the data included ANOVA and Pearson correlation analysis. RESULTS: One hundred and eight participants (36 with NTG, 35 with POAG, and 37 normal individuals) were enrolled. The CCT (NTG 514.8 1+/- 25.03 MUm; POAG 534.43 +/- 34.79 MUm; controls 536.70 +/- 32.11 MUm) was found to be thinner in patients with NTG compared with POAG and the control eyes (P=0.023; P=0.009). The AST (NTG 738.53 +/- 53.63 MUm; POAG 771.86 +/- 53.75 MUm; controls 783.62 +/- 57.03 MUm) was thinner in the patients with NTG compared with POAG and the normal controls (P=0.032; P=0.002). No significant difference in AST was found among the POAG and control eyes (P=0.636). A correlation between CCT and AST was found only among the patients with NTG (r=0.469, P=0.004). However, no correlation was observed between CCT and AST in patients with POAG and controls. CONCLUSIONS: Anterior scleral thickness was correlated with CCT in the NTG group, but this correlation was not observed among the POAG or control groups. PMID- 20577105 TI - Conjunctival inflammatory cells and their predictive role for deep sclerectomy in primary open-angle glaucoma and exfoliation glaucoma. AB - PURPOSE: To investigate the conjunctival inflammatory alterations of patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and correlate the findings with the success of deep sclerectomy (DS) surgery and with the patients' medical history. METHODS: Altogether 25 POAG and ExG patients of the prospective DS study were divided, based on the diagnosis and success of the operation, into 4 groups, POAG S (success), POAG F (failure), ExG S, and ExG F. Controls were obtained from other ophthalmologic surgery patients who did not have glaucoma, and their conjunctiva was examined to be normal. Inflammatory cell subtypes in the conjunctiva were identified and quantified by using immunohistochemistry and monoclonal antibodies: CD3 (T-lymphocyte marker), CD4 (T helper lymphocyte marker), CD8 (T-cytotoxic lymphocyte marker), CD20 (pan-B cell marker), CD38 (plasma cell marker), CD45RA (naive T-cell marker), and CD68 (macrophage marker). RESULTS: Higher numbers of inflammatory cells were found in the conjunctiva of the glaucoma patients on medical treatment compared with the normal conjunctiva of the controls. Moreover, T-lymphocytes, T-helper lymphocytes, T-cytotoxic lymphocytes, B cells, plasma cells, and macrophages were found in significantly higher numbers in patients in whom DS failed during the follow-up period of 2.5 years than those with surgical success. CONCLUSIONS: High numbers of cytotoxic and helper T-lymphocytes, plasma cells, and macrophages indicate a chronic inflammatory reaction in the conjunctiva of glaucoma patients. The chronic inflammation is most probably owing to the chronic topical treatment of the patients and seems to be a significant risk factor for DS surgery failure. PMID- 20577106 TI - Circumferential viscocanalostomy and suture canal distension (canaloplasty) for whites with open-angle glaucoma. AB - PURPOSE: To assess the safety and efficacy of canaloplasty (360-degree viscodilation and tensioning of the Schlemm canal) in Whites with open-angle glaucoma (OAG). METHODS: In a prospective study, 32 consecutive patients with medically uncontrolled OAG underwent primary canaloplasty with a follow-up time of more than 1 year. Laser goniopuncture was performed if postoperative intraocular pressure (IOP) was above 16 mmHg. IOP, number of antiglaucomatous medications, best-corrected visual acuity, and intraoperative and postoperative complications were recorded. Complete success was defined as an IOP <=21, 18, and 16 mm Hg without medications, and qualified success with or without medications, respectively. RESULTS: The mean IOP dropped from 27.3+/-5.6 mm Hg preoperatively to 12.8+/-1.5 mm Hg at 12 months and 13.1+/-1.2 mm Hg at 18 months (P<0.001). The complete success rate of an IOP <=21, 18, and 16 mm Hg was 93.8% [95% confidence interval (CI) 0.86-1.0], 84.4% (95% CI 0.73-0.98), and 74.9% (95% CI 0.61-0.92), respectively, at 12 months. Laser goniopuncture was performed on 6 eyes (18.1%) 3.3+/-2.1 months postoperatively. The mean IOP was 20.6+/-4.2 mm Hg before and 14.2+/-2.2 mm Hg after goniopuncture. The number of medications dropped from 2.7+/-0.5 before surgery to 0.1+/-0.3 after surgery (P<0.001). The postoperative best-corrected visual acuity at last visit (0.38+/-0.45; range: 0 to 1.8) was comparable with that of preoperative values (0.36+/-SD 0.37; range: 0 to 1.6) (P=0.42). In all but 1 eye, canaloplasty was completed. Minor intraoperative or postoperative complications like Descemet membrane detachment in 2 eyes, elevated IOP in 1 eye, and suprachoroidal passage of the catheter in 4 eyes were encountered. In 1 eye, circumferential cannulation of the Schlemm canal was impossible. CONCLUSIONS: Canaloplasty seems to be a promising and effective surgical procedure in Whites with OAG. Postoperative IOP levels are in the low-to mid-teens. The procedure can be regarded as safe, but has its own profile of complications. PMID- 20577107 TI - Intraoperative mitomycin C for nonpenetrating glaucoma surgery: a systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the efficacy and tolerability between nonpenetrating glaucoma surgery with (NPGS-MMC) and without (NPGS-noMMC) intraoperative mitomycin C application in the treatment of patients with open angle glaucoma. METHODS: Pertinent studies were selected through extensive searches of the Cochrane Library, PubMed, Embase, and Chinese Biomedicine Database. Eight controlled clinical trials meeting the predefined criteria were systematically reviewed by meta-analysis. The main outcome measures were percentage intraocular pressure reduction and complete success rate. The pooled estimates were carried out in RevMan version 5.0 software. RESULTS: The weighted mean differences of the percentage intraocular pressure reduction when comparing NPGS-MMC with NPGS-noMMC were 5.24% (95% confidence intervals: -3.24-13.72) at 6 months, 8.31% (4.33 to 12.30) at 12 months, 9.56% (4.88 to 14.24) at 24 months, and 14.45% (9.03 to 19.88) at 36 months. NPGS-MMC was associated with significant greater complete success rates compared with NPGS-noMMC, with a pooled risk ratio being 1.16 (1.05 to 1.27) at 6 months, 1.20 (1.05 to 1.38) at 12 months, 1.30 (1.05 to 1.61) at 24 months, and 1.36 (1.06 to 1.73) at 36 months. Intraoperative MMC was not associated with any drug-induced complications. CONCLUSIONS: The use of intraoperative MMC is a safe and effective additional step during nonpenetrating filtering surgery. PMID- 20577108 TI - Comparison of the prevalence of plateau iris configurations between angle-closure glaucoma and open-angle glaucoma using ultrasound biomicroscopy. AB - PURPOSE: To determine the prevalence of plateau iris configurations in acute primary angle-closure (APAC), chronic angle-closure glaucoma (CACG), and open angle glaucoma (OAG) eyes using ultrasound biomicroscopy. MATERIALS AND METHODS: The study included fellow eyes of 27 APAC patients, 26 OAG patients, and 26 CACG patients with no history of APAC. Patients with a history of earlier intraocular surgery or argon laser peripheral iridoplasty were excluded from the study. Eyes that had not undergone laser peripheral iridotomy were excluded from APAC and CACG groups. Radial scans were carried out using ultrasound biomicroscopy in all 4 quadrants. A plateau iris configuration within a quadrant was defined by the presence of an anteriorly positioned ciliary process, a narrow ciliary sulcus, a steeply rising peripheral iris, followed by a downward angulation from the corneoscleral wall and the presence of a flat iris plane. Eyes with plateau iris configurations were defined as those having at least 2 quadrants fulfilling these criteria. RESULTS: Plateau iris configurations were found in fellow eyes of 10 of 27 patients with (37.0%) APAC, 9 of 26 (34.6%) patients with CACG, and 5 of 26 (19.2%) patients with OAG. No significant difference in the prevalence of plateau iris configurations was observed among the 3 groups (P=0.314, chi2 test). CONCLUSIONS: Eyes with OAG had a higher rate of plateau iris configurations than expected. Longitudinal studies to evaluate plateau iris height are required to determine its significance in the pathogenesis of angle-closure glaucoma. PMID- 20577109 TI - SLT and adjunctive medical therapy: a prediction rule analysis. AB - PURPOSE: To investigate if specific classes of antiglaucoma medications have an influence on selective laser trabeculoplasty (SLT) success. METHODS: This retrospective prediction rule analysis investigated 120 eyes from 120 patients diagnosed with either open angle glaucoma or ocular hypertension, who underwent SLT treatment. Treatment success was defined as >=20% intraocular pressure (IOP) reduction at 3 and 6 months after the treatment date. Multivariate logistic regression analyses were performed to determine success predictors. RESULTS: Pre SLT IOP (up to 4 wk before SLT therapy) was the only independent predictor for >=20% IOP reduction with an odds ratio of 1.30 when controlling for pre-SLT antiglaucoma drops. The area under receiver operator characteristic curve was 0.777. CONCLUSIONS: Topical medications do not adversely, nor favorably, affect SLT success. SLT efficacy is positively associated with the degree of IOP elevation before SLT treatment. Pigmentation of the anterior chamber angle, class of antiglaucoma medications, diabetes, sex, corneal thickness, pseudophakia, diagnosis, washout of eye drops, and previous argon laser trabeculoplasty treatment are not associated with SLT treatment efficacy. PMID- 20577110 TI - Rasagiline-induced delay of retinal ganglion cell death in experimental glaucoma in rats. AB - PURPOSE: To evaluate the neuroprotective effect of rasagiline (N-propargyl-1 (R) aminoindan), a selective monoamine oxidase inhibitor, on the survival of retinal ganglion cells (RGCs) in glaucomatous rat eyes. Rasagiline is an FDA approved anti-Parkinson disease drug with neuroprotective capabilities that were shown in many models of brain damage. MATERIALS AND METHODS: The neuroprotective effect of daily intraperitoneal (IP) injections of rasagiline (0.5 mg/kg and 3 mg/kg) was evaluated and compared with saline injections using the translimbal photocoagulation model of experimental glaucoma in Wistar rats. Intraocular pressure (IOP) was measured before and immediately after the laser treatment, and then weekly. Seven weeks after the induction of glaucoma, the animals were killed, the eyes were enucleated and the retinas were prepared as whole mounts. Fluoro-gold had been injected into the superior colliculus 10 days before enucleation, and RGC survival was evaluated by counting the surviving labeled RGCs in a masked way. RESULTS: All rats (n=29) displayed significant IOP elevation and RGC damage. Seven weeks after the induction of glaucoma, the mean RGC survival was 43+/-8% in the rasagiline 3 mg/kg-treated group and 43+/-9% in the rasagiline 0.5 mg/kg-treated group compared with 23%+/-4% in the saline treated (control) group (P=0.01 and P=0.02, respectively). CONCLUSION: Systemic treatment with rasagiline significantly enhances the survival of RGCs in experimental glaucoma. PMID- 20577111 TI - A comparison of the intraocular pressure lowering effect of adjustable suture versus laser suture lysis for trabeculectomy. AB - PURPOSE: To compare the intraocular pressure lowering effect of adjustable sutures and laser suture lysis for trabeculectomy in eyes with primary open angle glaucoma. METHODS: Fifty patients with primary open angle glaucoma were studied. Eyes were assigned randomly to either trabeculectomy augmented with mitomycin C with adjustable sutures or with laser suture lysis. Patients were followed up for 12 months and success rate based on intraocular pressure was compared. Adjustable sutures were carried out as reported by Wells et al. RESULTS: Mean baseline intraocular pressure was 27.8+/-2.8 mm Hg in the adjustable suture group and 27.3+/-2.9 mm Hg in the laser suture lysis group (P=0.7). Mean postoperative intraocular pressure was 12.1+/-2.0 mm Hg at 3 months, 12.7+/-3.2 mm Hg at 6 months, and 12.9+/-3.4 mm Hg at 12 months in the adjustable suture group and 12.1+/-2.6 mm Hg at 3 months, 13.1+/-4.7 mm Hg at 6 months, and 13.4+/-3.5 mm Hg at 12 months in the laser suture lysis group. There was no significant difference in the mean intraocular pressure between the groups at any time point. At 12 months, 24 patients (96%) in the adjustable suture group and 23 patients (92%) in the laser suture lysis group achieved an intraocular pressure of >=20 mm Hg without medication and a minimum of 30 percent reduction (P=0.7). Significant anterior chamber reduction was found in no patient (0%) in the adjustable suture group and 6 patients (24%) in the laser suture lysis group after loosening of the adjustable sutures or laser suture lysis. CONCLUSIONS: There was no significant difference in hypotensive efficacy between adjustable suture group and laser suture lysis group. The use of adjustable sutures may reduce the incidence of shallow anterior chamber and hypotony after postoperative intraocular pressure lowering procedures. PMID- 20577112 TI - Perimetric progression in open angle glaucoma and the Visual Field Index (VFI). AB - PURPOSE: To evaluate the changes in the Visual Field Index (VFI) in eyes with perimetric glaucomatous progression, and to compare these against stable glaucoma patients. PATIENTS AND METHODS: Consecutive patients with open angle glaucoma with a minimum of 6 reliable visual fields and 2 years of follow-up were identified. Perimetric progression was assessed by 4 masked glaucoma experts from different units, and classified into 3 categories: "definite progression," "suspected progression," or "no progression." This was compared with the Glaucoma Progression Analysis (GPA) II and VFI linear regression analysis, where progression was defined as a negative slope with significance of <5%. RESULTS: Three hundred ninety-seven visual fields from 51 eyes of 39 patients were assessed. The mean number of visual fields was 7.8 (SD 1.1) per eye, and the mean follow-up duration was 63.7 (SD 13.4) months. The mean VFI linear regression slope showed an overall statistically significant difference (P<0.001, analysis of variance) for each category of progression. Using expert consensus opinion as the reference standard, both VFI analysis and GPA II had high specificity (0.93 and 0.90, respectively), but relatively low sensitivity (0.45 and 0.41, respectively). CONCLUSIONS: The mean VFI regression slope in our cohort of eyes without perimetric progression showed a statistically significant difference compared with those with suspected and definite progression. VFI analysis and GPA II both had similarly high specificity but low sensitivity when compared with expert consensus opinion. PMID- 20577113 TI - Topographic differences in the age-related changes in the retinal nerve fiber layer of normal eyes measured by Stratus optical coherence tomography. AB - PURPOSE: To determine whether there are regional differences in the age-related changes in peripapillary retinal nerve fiber layer (RNFL) thickness as measured by time-domain optical coherence tomography (OCT). METHODS: Fast peripapillary RNFL scans obtained with the Stratus time-domain OCT with nominal diameter of 3.46-mm centered on the optic disc were carried out on 425 normal participants over a wide age range. One eye was randomly selected for scanning or analysis. Average RNFL-, clock hour-, and quadrant-specific rates of RNFL thickness change were calculated and compared. RESULTS: The 425 study participants ranged in age from 18 to 85 years with mean (+/-SD) of 46 (+/-15) years. The mean (+/-SD) average measured RNFL thickness was 104.7 (+/-10.8) micrometers (MUm). The decline in the average RNFL thickness was 2.4 MUm per decade of age. Changes in RNFL thickness per decade of age ranged from -5.4 (P<0.001) at clock hour 1 to 0.9 (P=0.28) at clock hour 6. Similarly, the rate of thickness change per decade of age in the superior quadrant was -4.3 (P<0.001) versus -1.5 (P=0.006) in the inferior quadrant. The slopes of thinning superiorly and inferiorly were highly significantly different (P=0.001). CONCLUSIONS: The age-related decline in normal RNFL measurements does not occur at equal rates around the disc and occurs mainly superiorly. PMID- 20577114 TI - Does the enlargement of retinal nerve fiber layer defects relate to disc hemorrhage or progressive visual field loss in normal-tension glaucoma? AB - PURPOSE: We investigated the difference in clinical characteristics between cases with enlarged retinal nerve fiber layer defects (RNFLD) and stable RNFLDs in normal-tension glaucoma (NTG). PATIENTS AND METHODS: We retrospectively reviewed NTG patients that were diagnosed and followed up for at least 3 years at 1-month to 2-month intervals by the same examiner, and selected eyes with distinct RNFLD borders. Using fundus photographs, for which we extracted only a blue ingredient and processed it into black and white, we measured RNFLD angles and divided NTG cases into 2 groups, enlarged RNFLD and stable RNFLD, and compared the clinical characteristics between both groups. RESULTS: Ninety-three eyes from 93 patients (mean follow-up, 8.2 y) were selected and enlargement of RNFLD was detected in 55 eyes. Disc hemorrhage (DH) was found in 35 of 55 eyes (63.6%) in the enlarged group and in 6 of 38 eyes (15.8%) in the stable group (P<0.0001). Twenty-one eyes (38.2%) from the enlarged group exhibited recurrent DH. In 48 eyes (87.3%) from the enlarged group, the enlargement of RNFLD was toward the fovea. When DHs located apart from RNFLD were excluded, RNFLD enlarged in the direction of DH in 21 of 25 eyes (84.0%). The cumulative probability of non progression in the visual field was significantly lower in the enlarged group (10-year survival rate: 0.52+/-0.11) than in the stable group (10-year survival rate: 0.89+/-0.08) (P=0.0019). CONCLUSIONS: The enlargement of RNFLD in NTG was closely associated with DH occurrence and the deterioration of visual field. PMID- 20577115 TI - Psychometric evaluation of the Glaucoma Symptom Identifier. AB - OBJECTIVE: To evaluate the psychometric properties of the Glaucoma Symptom Identifier (GSI), a tool designed to assess multiple possible glaucoma symptoms and their impact on quality of life in clinical practice. We sought to address the need for better methods to assess visual function related to quality of life of glaucoma patients with a tool to show to both physicians and their patients that glaucoma is not an asymptomatic disease. The development process was to provide comprehensive assessment in 1 page of the impact of glaucoma on patients' quality of life by including an exhaustive list of unique and nonredundant items. DESIGN: Cross-sectional online survey. PARTICIPANTS: Seven hundred and eighteen individuals with a self-reported diagnosis of glaucoma, who were at least 40 years of age. METHODS: The impact of glaucoma was assessed by asking study participants the degree of difficulty they experience on a number of tasks. Item response theory was used to psychometrically evaluate the GSI. Scores on the GSI and the SF-12, a generic quality-of-life instrument, were compared. MAIN OUTCOME MEASURES: Items in the GSI were categorized in terms of their ability to capture glaucoma impact on quality of life across the population range of subjects from mild-to-severe glaucoma severity. RESULTS: The GSI showed good reliability, and convergent and discriminant validity. Items in the GSI captured glaucoma impact on quality of life over an adequate range of disease severity. Potential improvements to the existing questionnaire were identified using item response theory modeling results and respondents' feedback on the survey. CONCLUSIONS: Our findings suggest that the GSI is a psychometrically valid tool, adequate for glaucoma patients' self-administration within a clinician's routine practice to help both the patient and physician assess the patient's current and potential future symptoms of glaucoma. PMID- 20577117 TI - Diagnostic power of optic disc morphology, peripapillary retinal nerve fiber layer thickness, and macular inner retinal layer thickness in glaucoma diagnosis with fourier-domain optical coherence tomography. AB - PURPOSE: To evaluate the capability of the optic disc, peripapillary retinal nerve fiber layer (P-RNFL), macular inner retinal layer (M-IRL) parameters, and their combination obtained by Fourier-domain optical coherent tomography (OCT) in differentiating a glaucoma suspect from perimetric glaucoma. METHODS: Two hundred and twenty eyes from 220 patients were enrolled in this study. The optic disc morphology, P-RNFL, and M-IRL were assessed by the Fourier-domain OCT (RTVue OCT, Model RT100, Optovue, Fremont, CA). A linear discriminant function was generated by stepwise linear discriminant analysis on the basis of OCT parameters and demographic factors. The diagnostic power of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis. The diagnostic power in the clinically relevant range (specificity >= 80%) was presented as the partial area under the ROC curve (partial AROC). RESULTS: The individual OCT parameter with the largest AROC and partial AROC in the high specificity (>= 80%) range were cup/disc vertical ratio (AROC = 0.854 and partial AROC = 0.142) for the optic disc parameters, average thickness (AROC = 0.919 and partial AROC = 0.147) for P-RNFL parameters, inferior hemisphere thickness (AROC = 0.871 and partial AROC = 0.138) for M-IRL parameters, respectively. The linear discriminant function further enhanced the ability in detecting perimetric glaucoma (AROC = 0.970 and partial AROC = 0.172). CONCLUSIONS: Average P-RNFL thickness is the optimal individual OCT parameter to detect perimetric glaucoma. Simultaneous evaluation on disc morphology, P-RNFL, and M-IRL thickness can improve the diagnostic accuracy in diagnosing glaucoma. PMID- 20577116 TI - The influence of topical diclofenac sodium on the ocular hypotensive effect of latanoprost in glaucoma patients. AB - PURPOSE: To evaluate the effect of diclofenac sodium 0.1% on reducing intraocular pressure (IOP) by latanoprost 0.005% in glaucoma patients. PATIENTS AND METHODS: Twenty-two patients with bilateral primary open angle glaucoma were enrolled in this study. All patients had been given only latanoprost for at least 4 weeks. Topical diclofenac sodium was additionally applied to one eye (dicloptin group), whereas hydroxypropyl methyl cellulose was administered into the other eye (control group); both 4 times a day for 2 weeks. IOP measurement was performed before and 2 weeks after the administrations, and also 2 weeks after discontinuing additional ophthalmic solutions. RESULTS: No significant difference was observed in the IOPs before additional administration of ophthalmic solution between the dicloptin group and the control group (P=0.47). Additional administration of diclofenac sodium increased mean IOP from 15.73+/-1.75 to 17.32+/-2.23 mm Hg (P=0.01). This increase was reversed 2 weeks after discontinuing additional solutions (P=0.80); however, no significant difference in mean IOP was observed in the control group after administration and after discontinuing the additional medication (P=0.94 and 0.84, respectively). CONCLUSIONS: Topical diclofenac sodium may interfere with the IOP lowering effect of latanoprost in glaucoma patients; therefore this interference should be noted in coadministration of these drugs. PMID- 20577118 TI - Angiotensin II contributes to the increased baseline leg vascular resistance in spinal cord-injured individuals. AB - OBJECTIVE: Spinal cord-injured (SCI) individuals demonstrate an increased baseline leg vascular resistance (LVR). In addition, despite the lack of sympathetic control, an increase in LVR is observed during orthostatic challenges. On the basis of the vasoconstrictive characteristics of angiotensin II, we examined the hypothesis that angiotensin II contributes to the LVR at baseline and during head-up tilt (HUT) in SCI individuals. METHODS: Supine baseline leg and forearm blood flow were measured using venous occlusion plethysmography and leg blood flow during 30 degrees HUT using duplex ultrasound. Measurements were performed before and 4 h after an angiotensin II antagonist (irbesartan, 150 mg) administered in eight SCI individuals and eight age-matched and sex-matched able-bodied controls. Vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. RESULTS: Angiotensin II blockade significantly decreased baseline LVR in SCI individuals (P = 0.02) but not in controls, whereas no changes in forearm vascular resistance were found in both groups. Angiotensin II blockade did not alter the increase in LVR during HUT in SCI individuals nor in controls. CONCLUSION: Our results indicate that angiotensin II contributes to the increased baseline LVR in SCI individuals. As angiotensin II does not contribute to forearm vascular resistance, the contribution to LVR may relate to the extreme inactivity of the legs in SCI individuals. Angiotensin II does not contribute to the increase in LVR during HUT in SCI individuals nor in controls. PMID- 20577120 TI - Blood pressure reduction and cardiovascular prevention: meta-regression using ordered categorical (ordinal) event data. AB - BACKGROUND: Blood pressure (BP)-lowering trials studying efficacy mostly assesses binary outcome events, for example stroke/no stroke. Analysis of ordered categorical vascular events (e.g. three levels: fatal stroke/nonfatal stroke/no stroke) provides information on severity and is more powerful statistically than analyses using binary data, as used in previous meta-regression analyses of BP lowering. METHODS: Summary data on stroke, myocardial infarction, and combined vascular events were obtained from published BP-lowering trials. Ordinal and binary odds ratios were calculated. The relationship between the difference in BP and treatment odds ratio was assessed using meta-regression. RESULTS: Thirty eight trials involving 180 804 patients were included. A 'U' or 'J'-shaped relationship was found between on-treatment BP difference and three level ordinal stroke, ordinal myocardial infarction, and ordinal combined vascular outcome. Similar relationships were noted for binary stroke, myocardial infarction, and combined vascular outcome. Meta-regression curves for three level ordinal analyses were similar in shape and position to that for binary analyses. CONCLUSIONS: Meta-regression using ordinal outcomes in hypertension trials is practical and gives comparable values for the odds ratio as found in analyses based on binary outcomes. However, trials and meta-analyses reporting ordinal outcomes provide additional information in particular that lowering BP reduces both the severity and frequency of fatal and recurrent stroke. Trials should report data so that ordinal analyses may be performed. PMID- 20577119 TI - Pharmacogenetic association of hypertension candidate genes with fasting glucose in the GenHAT Study. AB - BACKGROUND: Several clinical studies report increased risk of diabetes mellitus with pharmacologic treatment for hypertension (HTN). HTN genes may modify glycemic response to antihypertensive treatment. METHOD: The current study examined the association of 24 single nucleotide polymorphisms (SNPs) in 11 HTN candidate genes with fasting glucose measured at 2, 4, and 6 years after treatment initiation. The study sample included participants free of diabetes at baseline in the Genetics of Hypertension Associated Treatment (GenHAT) study (N = 9309). GenHAT participants were randomized to receive treatment with a diuretic (chlorthalidone), calcium channel blocker (amlodipine), or angiotensin-converting enzyme (ACE) inhibitor (lisinopril). Mixed models for repeated measures were employed to test for gene and pharmacogenetic associations with fasting glucose during follow-up. RESULTS: Fasting glucose at year 2 increased on average 6.8, 4.8 and 3.0 mg/dl from baseline in the chlorthalidone, amlodipine and lisinopril groups, respectively. Carrying the I allele (rs1799752) of the ACE I/D polymorphism was associated with lower fasting glucose levels (P = 0.02). Additionally, an ACE promoter polymorphism (-262, rs4291) was associated with lower fasting glucose for the model AA/AT vs. TT, which remained significant after correction for multiple testing (P = 0.001). Finally, a SNP in the alpha subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A, rs2228576) modified the association of amlodipine vs. chlorthalidone treatment with fasting glucose (P < 0.001). CONCLUSION: Further examination of these genes and their relationships with cardiometabolic disease could foster development of pharmacogenetic guidelines aimed to prevent increases in fasting glucose during antihypertensive treatment. PMID- 20577121 TI - Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials. AB - OBJECTIVE: Reported effects of different soy products on blood pressure vary. This systematic review and meta-analysis was performed to clarify the effects of soy isoflavone extract supplements on systolic and diastolic blood pressure (SBP and DBP) in adult humans. METHODS: PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant randomized placebo-controlled trials. Study data and indicators of methodological validity were independently extracted by two authors using predefined data fields. Meta-analysis was carried out in Review Manager 5.0.22. RESULTS: Searches identified 3740 articles, of which 14 randomized controlled trials (789 participants) were included. Daily ingestion of 25-375 mg soy isoflavones (aglycone equivalents) for 2-24 weeks significantly decreased SBP by 1.92 mmHg (95% confidence interval -3.45 to -0.39; P = 0.01) compared with placebo (heterogeneity P = 0.39, fixed effect model) in adults with normal blood pressure and prehypertension. The effect was not lost on sensitivity analysis. Subgroup analyses suggest greater effects in studies longer than 3 months, in Western populations, at lower doses, and in studies at lower risk of bias. Soy isoflavones did not affect DBP [-0.13 (95% confidence interval -1.03 to 0.78) mmHg, P = 0.78; heterogeneity P = 0.20, fixed effect model]. CONCLUSION: Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans, and no dose-response relationship was observed. Further studies are needed to address factors related to the observed effects of soy isoflavones on SBP and to verify the effect in hypertensive patients. PMID- 20577122 TI - Differential effects of insulin on sympathetic nerve activity in agouti obese mice. AB - OBJECTIVE: Hyperinsulinemia, which often coexists with obesity and type 2 diabetes, is a major risk factor for cardiovascular disease and thought to promote hypertension through the sympathetic effects of insulin. Here, we examined the effect of insulin on regional sympathetic nerve activity (SNA) in obesity. METHODS: Glucose and insulin tolerance tests were performed to examine insulin sensitivity in agouti obese mice. We used also multifiber recording to compare the regional SNA response to intracerebroventricular (ICV) insulin between lean and agouti obese mice. RESULTS: Agouti obese mice have significantly elevated levels of blood glucose and plasma insulin associated with glucose intolerance and insulin resistance. In lean mice, ICV administration of insulin (20 and 100 microU) caused a dose-dependent increase in SNA subserving hindlimb, kidney and brown adipose tissue (BAT). Of note, the regional SNA responses to insulin were differentially altered in agouti obese mice. Whereas lumbar SNA response to insulin was intact in the obese mice, renal and BAT sympathetic activation to insulin were significantly attenuated in these agouti obese mice. Finally, we assessed the role of phosphoinositol-3 kinase (PI3K) signaling pathway in mediating sympathetic activation to insulin in obesity. Notably, ICV pretreatment with a PI3K inhibitor (LY294002) blocked the increase in lumbar SNA induced by ICV insulin in lean and agouti obese mice. CONCLUSIONS: Our data suggest a differential regulation by insulin of sympathetic outflow to peripheral tissues in obesity. Our findings also demonstrate the importance of PI3K in lumbar sympathetic activation to insulin in obesity. PMID- 20577123 TI - Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats. AB - OBJECTIVE: The formation of cerebral aneurysms is associated with endothelial damage and macrophage migration. Hypothesizing that the opening of tight junctions due to the disappearance of the tight junction proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia allows macrophage migration, leading to cerebral aneurysm formation, we investigated the role of tight junction proteins. METHODS: The vascular wall of female rats subjected to hypertension, oophorectomy (OVX), and hemodynamic stress to induce cerebral aneurysms was evaluated morphologically, immunohistochemically, and by quantitative RT-PCR. We also assessed the regulation of tight junction proteins in human brain endothelial cells (HBECs). RESULTS: In the very early stage before aneurysm formation, the expression of occludin and ZO-1 was reduced in injured endothelial cell junctions exhibiting gaps. In the course of aneurysmal progression their reduction progressed and was correlated with macrophage migration. In hypertension along with OVX rats we observed an increase in angiotensin II and the degradation molecules matrix metalloproteinase-9 (MMP-9), nicotinamide-adenine dinucleotide phosphate oxidases and monocyte chemoattractant protein-1. The mineralocorticoid receptor blocker eplerenone increased occludin and ZO-1 expression; this was associated with a reduction in angiotensin II and the degradation molecules and resulted in the inhibition of macrophage exudation and aneurysm formation. In HBECs, occludin and ZO-1 downregulation by angiotensin II and estrogen deficiency was reversed by eplerenone, the MMP inhibitor SB3CT, and apocynin. Our results suggest that macrophage migration is associated with the reduction in tight junction proteins induced by the degradation molecules. CONCLUSION: In rats, the destruction of tight junctions may facilitate macrophage migration and cerebral-aneurysm formation. PMID- 20577124 TI - Is leptin involved in phagocytic NADPH oxidase overactivity in obesity? Potential clinical implications. AB - OBJECTIVES: Hyperleptinemia and oxidative stress play a major role in the development of cardiovascular diseases in obesity. This study aimed to investigate whether there is a relationship between plasma levels of leptin and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and its potential relevance in the vascular remodeling in obese patients. METHODS: The study was performed in 164 obese and 94 normal-weight individuals (controls). NADPH oxidase activity was evaluated by luminescence in phagocytic cells. Levels of leptin were quantified by ELISA in plasma samples. Carotid intima-media thickness (cIMT) was measured by ultrasonography. In addition, we performed in-vitro experiments in human peripheral blood mononuclear cells and murine macrophages. RESULTS: Phagocytic NADPH oxidase activity and leptin levels were enhanced (P < 0.05) in obese patients compared with controls. NADPH oxidase activity positively correlated with leptin in obese patients. This association remained significant in a multivariate analysis. cIMT was higher (P < 0.05) in obese patients compared with controls. In addition, cIMT also correlated positively with leptin and NADPH oxidase activity in obese patients. In-vitro studies showed that leptin induced NADPH oxidase activation. Inhibition of the leptin-induced NADPH oxidase activity by wortmannin and bisindolyl maleimide suggested a direct involvement of the phosphatidylinositol 3-kinase and protein kinase C pathways, respectively. Finally, leptin-induced NADPH oxidase activation promoted macrophage proliferation. CONCLUSIONS: These findings show that phagocytic NADPH oxidase activity is increased in obesity and is related to preclinical atherosclerosis in this condition. We also suggest that hyperleptinemia may contribute to phagocytic NADPH oxidase overactivity in obesity. PMID- 20577125 TI - Structural alterations in subcutaneous small resistance arteries predict changes in the renal function of hypertensive patients. AB - BACKGROUND: We have previously demonstrated that structural alterations in subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen ratio (M/L), are a potent predictor of cardiovascular events, and that a close correlation exists between serum creatinine and M/L. The aim of the present study was to assess whether M/L of subcutaneous small resistance arteries may predict subsequent changes in renal function in hypertensive patients. METHOD: Sixty participants (13 normotensive participants and 47 hypertensive patients) underwent a biopsy of subcutaneous fat. Resistance sized arteries were dissected and mounted on a wire myograph, and M/L was measured. Patients were re-evaluated after a mean follow-up period of 8.6 years. Serum creatinine, blood urea nitrogen, and uric acid were measured; glomerular filtration rate (eGFR) was estimated according to Modification of Diet in Renal Disease formula. RESULTS: At baseline, we observed significant correlations between M/L and serum creatinine, eGFR, blood urea nitrogen, systolic, diastolic, mean, and pulse pressure. In addition, we observed significant correlations between M/L and serum creatinine at follow-up (r = 0.57; P < 0.001), percentage changes in serum creatinine (r = 0.46; P < 0.001), eGFR at follow-up (r = -0.43; P < 0.001); percentage changes in eGFR, yearly changes in eGFR, blood urea nitrogen at follow-up, and uric acid at follow-up. A multivariate analysis in which all common cardiovascular risk factors were included showed that M/L ratio is the most potent predictor of changes in renal function. CONCLUSION: Our data suggest that structural alterations in subcutaneous small arteries may predict the time course of changes in renal function during a follow-up period of about 9 years. PMID- 20577126 TI - The association between fatty liver disease and blood pressure in a population based prospective longitudinal study. AB - OBJECTIVE: The aim of the present study was to investigate the association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population sample with prospective 5-year follow-up examinations. DESIGN AND METHODS: We used data from the Study of Health in Pomerania, conducted in the northeastern part of Germany. The study population comprised 3191 individuals aged 20-79 years. FLD was defined as the presence of a hyperechogenic pattern of the liver and increased serum alanine transferase (ALT) levels. RESULTS: Multivariable analyses revealed that FLD was associated with increased DBP and hypertension at baseline and with increased SBP and hypertension at follow-up. In individuals with FLD, the chance of hypertension at baseline and follow-up was three-fold higher [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.3-6.2 and OR 3.1; 95% CI 1.7-5.8, respectively] compared to individuals without FLD. In the subgroup of individuals not receiving antihypertensive medication, FLD was associated with all BP-related variables at baseline and follow-up. Analyses further suggest that these associations were independent of alcohol consumption and further confounders. CONCLUSION: FLD defined by liver hyperechogenity and increased ALT levels is associated with progression of BP over time and incident hypertension. In individuals with FLD, BP should be checked regularly and interventions addressing behavioural risk factors for FLD and hypertension should be initiated if necessary. Ultrasound should be implemented as a method to detect FLD in individuals with increased ALT levels in routine medical care. PMID- 20577127 TI - Differential effects of acute and sustained cyclosporine and tacrolimus on sympathetic nerve activity. AB - BACKGROUND: We studied the effect of acute and sustained cyclosporine and tacrolimus on muscle sympathetic nerve activity (MSNA) in groups of healthy male volunteers. METHODS AND RESULTS: Acute cyclosporine in normal dose (2.5 mg/kg) increased MSNA from 11 +/- 6 to 19 +/- 8 bursts/min (P < 0.05). Acute cyclosporine in high dose (10 mg/kg) increased MSNA from 13 +/- 6 to 25 +/- 4 bursts/min (P < 0.05) and increased heart rate and mean arterial pressure (heart rate from 64 +/- 8 to 74 +/- 6 b.p.m., MAP from 92 +/- 10 to 105 +/- 8 mmHg; both P < 0.05). Sustained cyclosporine (2.5 mg/kg b.i.d. for 2 weeks) suppressed MSNA from 14 +/- 6 to 8 +/- 7 bursts/min (P < 0.05). Blood pressure increased from 89 +/- 6 to 98 +/- 6 mmHg (P < 0.05). Body weight increased and plasma renin activity was suppressed. Acute tacrolimus in regular dose (0.05 mg/kg) and high dose (0.20 mg/kg) had no effect on MSNA and blood pressure. Sustained tacrolimus (0.05 mg/kg b.i.d. for 2 weeks) had no effect on blood pressure, body weight and plasma renin activity, but decreased MSNA from 14 +/- 6 to 8 +/- 5 bursts/min (P < 0.05). CONCLUSION: Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear. PMID- 20577128 TI - Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. AB - BACKGROUND: Perivascular adipose tissue secretes an adipocyte-derived relaxing factor (ADRF) that opens voltage-dependent K (Kv) channels in peripheral arteries. We studied the role of KCNQ-type Kv channels and tested the hypothesis that hydrogen sulfide (H2S) could be an ADRF. METHODS: We performed isometric contraction studies on systemic arteries of rats and mice. RESULTS: In mesenteric arteries and aortas without perivascular adipose tissue, the KCNQ channel openers retigabine, VRX0530727, VRX0621238, and VRX0621688 produced concentration dependent vasorelaxation; VRX0621688 was the most potent vasodilator. The KCNQ inhibitor XE991 (30 micromol/l) blocked the effects of both the drugs and ADRF. Inhibitors of cystathionine gamma lyase (CSE) beta-cyano-L-alanine (BCA, 5 mmol/l) and 4-propargyl glycine (PPG, 10 mmol/l) also blocked the relaxations. CSE is expressed in perivascular adipose tissue and endogenously generates H2S. The H2S donor NaHS produced concentration-dependent vasorelaxation, which was also blocked by XE991. The vasodilatory capacities of retigabine, VRX0530727, VRX0621238, and VRX0621688 were preserved following inhibition of H2S generation in perivascular fat. CONCLUSION: We suggest that KCNQ channel opening is a powerful mechanism to produce vasorelaxation of systemic arteries in rats and mice. Furthermore, KCNQ channels play a major role in the paracrine control of vascular tone by perivascular adipose tissue, which is at least in part mediated or modulated by H2S. In conditions of reduced H2S release from perivascular adipose tissue, these paracrine effects can be mimicked by synthetic KCNQ channel openers. PMID- 20577129 TI - Increased pulse wave velocity and not reduced ejection fraction is associated with impaired baroreflex control of heart rate in congestive heart failure. AB - BACKGROUND: It is known that baroreflex sensitivity (BRS) is impaired in cardiac patients with myocardial infarction (MI). Nevertheless, it is unknown whether factors other than a reduced ejection fraction play a role in the baroreflex impairment of these patients. METHODS AND RESULTS: Heart failure patients [congestive heart failure (CHF), n = 31, age 63 +/- 1.2 years, mean +/- SEM)], age-matched controls (n = 29) and coronary artery disease (CAD) patients without MI (n = 29) had RR interval and arterial blood pressure (BP) continuously monitored. Baroreflex function was assessed by the slope of the regression of RR interval, and BP responses to graded (-10, -20 and -40 mmHg) neck suction stimulation, the slope of bradycardic or tachycardic responses to spontaneous increases or reductions of SBP (sequence analysis) and the baroreflex efficiency index. Pulse wave velocity (PWV) was also measured.Compared with controls, CHF patients had RR interval and BP reflex responses to neck suction reduced by -36 and -54%, respectively (P < 0.01). By contrast, no differences were found between CHF and CAD patients. Similar reductions were observed for the sequence analysis (P < 0.01) in both CHF and CAD patients. Multiple regression analysis showed that in CHF and CAD patients, PWV and SBP and not ejection fraction were correlated with BRS. CONCLUSION: The baroreflex function is impaired in CHF patients, the extent and the degree of baroreflex impairment being similar to that of CAD patients without MI. In CHF and CAD patients, the baroreflex impairment correlates significantly with the increased PWV and not with ejection fraction. PMID- 20577130 TI - Continuous positive airway pressure treatment in sleep apnea patients with resistant hypertension: a randomized, controlled trial. AB - OBJECTIVES: This controlled trial assessed the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH). METHODS: We evaluated 96 patients with resistant hypertension, defined as clinic BP at least 140/90 mmHg despite treatment with at least three drugs at adequate doses, including a diuretic. Patients underwent a polysomnography and a 24-h ambulatory BP monitoring (ABPM). They were classified as consulting room or ABPM-confirmed resistant hypertension, according to 24-h BP lower or higher than 125/80 mmHg. Patients with an apnea hypopnea index at least 15 events/h (n = 75) were randomized to receive either CPAP added to conventional treatment (n = 38) or conventional medical treatment alone (n = 37). ABPM was repeated at 3 months. The main outcome was the change in systolic and diastolic BP. RESULTS: Sixty-four patients completed the follow-up. Patients with ABPM-confirmed resistant hypertension treated with CPAP (n = 20), unlike those treated with conventional treatment (n = 21), showed a decrease in 24-h diastolic BP (-4.9 +/- 6.4 vs. 0.1 +/- 7.3 mmHg, P = 0.027). Patients who used CPAP > 5.8 h showed a greater reduction in daytime diastolic BP {-6.12 mmHg [confidence interval (CI) -1.45; -10.82], P = 0.004}, 24-h diastolic BP (-6.98 mmHg [CI -1.86; -12.1], P = 0.009) and 24-h systolic BP (-9.71 mmHg [CI -0.20; 19.22], P = 0.046). The number of patients with a dipping pattern significantly increased in the CPAP group (51.7% vs. 24.1%, P = 0.008). CONCLUSION: In patients with resistant hypertension and OSA, CPAP treatment for 3 months achieves reductions in 24-h BP. This effect is seen in patients with ABPM-confirmed resistant hypertension who use CPAP more than 5.8 h. PMID- 20577131 TI - Chiasmal stroke following open-heart surgery. AB - A 62-year-old man awoke from aortic valve replacement surgery with a total loss of vision in his right eye and a temporal visual field defect in his left eye. Automated visual field examination confirmed a right-sided anterior junction syndrome, and a right-sided chiasmal infarct was demonstrated by MRI. Although rare, chiasmal stroke is a potential complication of open-heart surgery. PMID- 20577132 TI - Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction. AB - OBJECTIVE: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. METHODS: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. RESULTS: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 microg/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. CONCLUSIONS: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women. PMID- 20577133 TI - Netrin G-2 ligand mRNA is downregulated in spinal motoneurons after sciatic nerve lesion. AB - Netrin G-2 ligand (NGL-2) and synaptic adhesion like molecules induce synapses in vitro. We investigated the expression of these molecules in a model of CNS synaptic detachment and restoration in vivo. After axotomy of spinal motoneurons, synapses are lost from the somata of lesioned motoneurons. We could not detect any synaptic adhesion like molecule mRNA in the spinal cord, but signal for NGL-2 mRNA was seen in motoneurons. The signal for NGL-2 decreased after sciatic nerve transection and sciatic nerve crush. After regeneration, the levels of NGL-2 mRNA were partially restored after sciatic nerve transection, but completely restored after sciatic nerve crush. We conclude that axotomized motoneurons decrease their NGL-2 expression and that the restoration of NGL-2 expression mirrors the restoration of synaptic inputs. PMID- 20577134 TI - Brain oscillatory 4-30 Hz electroencephalogram responses in adolescents during a visual memory task. AB - Brain oscillatory responses of the 4-30 Hz electroencephalogram frequencies were assessed in 12 adolescents (mean age 14 years) during a visual N-back task with four memory load conditions (0-back, 1-back, 2-back, and 3-back). Theta frequency range (approximately 4-6 Hz) responses were elicited in all memory load conditions. The magnitude and duration of alpha frequency range (approximately 8 12 Hz) responses varied as a function of memory load. Beta frequency range (approximately 15-20 Hz) responses were modulated by both task difficulty and cognitive strategy. The differences between the memory load conditions were most prominent between the 0-back and 1-back conditions in the approximately 10 and 20 Hz electroencephalogram frequencies. Dynamic alpha and beta rhythm brain oscillatory responses are related to the cognitive processes in adolescence. PMID- 20577135 TI - Bilateral orbital bone infarction in sickle-cell disease. AB - This is a case of a 2-year-old boy with sickle cell disease who presented with bilateral eyelid swelling, limited extraocular motility, and lateral subperiosteal fluid collection associated with bilateral lateral orbital wall infarctions on MRI. The patient was managed medically with intravenous fluids, analgesics, broad-spectrum antibiotics, systemic steroids, and clinically improved. Patients with sickle cell disease are susceptible to infarction of the orbital bones during vaso-occlusive crises. Orbital wall infarction can lead to acute proptosis and restricted extraocular motility. Orbital wall infarction should be considered in sickle cell patients with orbital diseases so that appropriate treatment can be instituted promptly to prevent the serious sequelae of orbital compression syndrome. PMID- 20577136 TI - Acyclovir use in sick infants. AB - BACKGROUND: Infantile herpes simplex virus encephalitis (HSVE) infection remains a significant cause of morbidity and mortality. Diagnosis is often difficult in this population, where a specific pattern of clinical and laboratory signs are lacking. This often results in unnecessary treatment of infants with empiric acyclovir. This study evaluates the use of empiric acyclovir at the Kentucky Children's Hospital and attempts to correlate any laboratory or clinical findings that may be highly suggestive of HSVE. METHODS: Medical records of infants younger than 1 year admitted and treated with acyclovir were evaluated for any consistent pattern of clinical findings suggestive of HSVE. Specifically, serum and cerebrospinal fluid (CSF) white blood cell counts, red blood cell counts, cerebrospinal glucose and protein, and clinical neurological findings upon admission were evaluated. RESULTS: Two hundred eighteen infants were identified and included in the study. Three infants were identified with polymerase chain reaction-positive HSVE. Only CSF leukocytosis was consistent among HSVE-positive infants. All infants with HSVE exhibited generalized neurological findings. Neither hemorrhagic CSF nor focal neurological findings were indicative of HSVE infection. DISCUSSION: Herpes simplex virus encephalitis has a very low prevalence within this population. Clinically significant neurological findings as well as specific risk factors must be present to consider treatment with empiric acyclovir. Apnea and focal seizures are not specific risk factors for herpetic meningitis in infants. Lack of a CSF leukocytosis is a strong negative predictor for HSVE, and hemorrhagic fluid is not specific for HSVE. PMID- 20577137 TI - Pediatric mock code curriculum: improving resident resuscitations. AB - OBJECTIVES: Resuscitation of the acutely ill child is a necessary skill for pediatric residents. The effects of a hospital-wide mock code program on involvement, anxiety, and leadership have not been studied. We hypothesized that after 1 year of mock codes, pediatric residents would report (1) increased participation, (2) decreased anxiety and increased comfort with knowledge, and (3) increased likelihood of leading and feeling capable of running a code. METHODS: In this cross-sectional study of pediatric residents, anonymous surveys evaluated involvement, comfort, and leadership in codes before and 1 year after a monthly mock code curriculum was incorporated into the resident educational curriculum. The survey measured residents' involvement in actual and mock codes and levels of anxiety, knowledge, and leadership ability during codes. RESULTS: Approximately 60 residents returned completed survey forms each year. Attendance and participation at actual codes were not significantly changed between years. For mock codes, there was a significant change (P < 0.001) in both observation and participation. After 1 year, residents reported a statistically significant increase in their comfort with knowledge during a code (odds ratio, 2.5; 95% confidence interval, 1.2-5.2). They also reported a decrease in anxiety and felt more capable of running a code, although these numbers were not statistically significant. CONCLUSIONS: One year after starting a mock code program, residents attended more mock codes and reported more comfort with knowledge in codes. A continued monthly mock code program will provide residents with critical skills training and experience and may translate into active participation, increased leadership, and decreased anxiety in actual codes. PMID- 20577138 TI - "Traumatic tap" proportion in pediatric lumbar puncture. AB - OBJECTIVES: To determine the frequency of "traumatic" or "bloody" tap when pediatric lumbar puncture is performed by a physician who has completed training and performs the procedure frequently. METHODS: The author identified 100 sequential patients presenting to a pediatric emergency department requiring lumbar puncture for clinical indications. Demographic information, cerebrospinal cell counts, and other relevant data were later obtained by retrospective chart review. Cell count results were categorized according to several previously used criteria: greater than 400, greater than 1000, and greater than 10,000/unsuccessful. RESULTS: One procedure yielded only a small amount of bloody fluid on which no cell count was performed. The remaining 99 procedures yielded red blood cell counts less than 1000. CONCLUSIONS: The proportion of bloody or traumatic results from pediatric lumbar puncture reported from pediatric training centers is typically in the 20% to 30% range. This represents an overestimation of a more ideal proportion possible when the procedure is performed by a physician who has completed training and performs the procedure frequently. PMID- 20577139 TI - A simulation-based acute care curriculum for pediatric emergency medicine fellowship training programs. AB - OBJECTIVES: Currently, many pediatric hospitals are using simulation technology to teach trainees the skills required to effectively succeed in managing critically ill patients. Unfortunately, no curricula integrating the use of simulation have been described for pediatric emergency medicine (PEM) fellowship programs. Our objective was to outline our experience with the development, integration, and evaluation of a simulation-based, acute care curriculum into our current PEM fellowship training program. METHODS: Using the American Board of Pediatrics and the Royal College of Physicians and Surgeons of Canada learning objectives for PEM as a guide, 12 modules composed of 43 scenarios were developed to address the skill sets required for PEM fellows. Six modules were identified as "core," allocated for completion in year 1 of fellowship, whereas the remaining modules were "subspecialty," designed for completion in year 2 of training. A 12-question survey (5-point Likert scale) was used to evaluate trainee satisfaction with regard to 4 domains: level of realism, utility of debriefing, quality of instruction, and overall satisfaction. RESULTS: A total of 66 surveys were collected between March and July 2007. Twenty-five surveys were completed by PEM fellows. Trainees responded favorably for all 4 domains, reporting that the new simulation curriculum provided realistic scenarios with high-quality debriefing, instruction, and an overall excellent learning experience. CONCLUSIONS: We have successfully integrated a simulation-based acute care curriculum into our PEM fellowship program. Satisfaction ratings were high for this program. Research to assess educational outcomes related to this curriculum is necessary. PMID- 20577140 TI - Occult pneumonia in infants with high fever without source: a prospective multicenter study. AB - BACKGROUND: The prevalence of pneumonia in infants with high fever without source (FWS; temperature, > or =39.0 degrees C) and a white blood cell (WBC) count greater than 20 x 10(9)/L (occult pneumonia) has been reported to be 20% before the introduction of the 7-valent pneumococcal conjugated vaccine (PCV7). This is the main reason for carrying out chest x-ray (CXR) on infants with high FWS. The aims of this study were to establish the prevalence of occult pneumonia in well appearing infants with high FWS (temperature, > or =39.0 degrees C) and a WBC count greater than 20 x 10(9)/L in the era of PCV7 and to analyze the value of WBC, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as predictors of the risk of occult pneumonia in these patients. PATIENTS AND METHODS: We conducted a multicenter prospective study in 4 pediatric emergency departments including children younger than 36 months with FWS (temperature, > or =39.0 degrees C) and a WBC count higher than 20 x 10(9)/L on whom a CXR was performed in the absence of respiratory findings. Physicians completed a questionnaire when observing the infant, and the attending physician or, when in doubt, the radiologist interpreted the CXR. Multivariable binary logistic regression was used to estimate the adjusted relative influences of the aforementioned factors on the prevalence of radiological pneumonia. RESULTS: During an entire year (September 2006 to September 2007), we included 188 infants (aged 1-36 months; 56.2% were males) with high FWS and a WBC count greater than 20 x 10(9)/L (range, 20-44.7 x 10(9)/L) on whom a CXR was performed. Of the 188 chest radiographs obtained, 37 (19.7%) were interpreted by the radiologist. Consolidation in the chest radiographs was detected in 25 (13.3%). The probability of an infant with high FWS and WBC of 20 x 10(9)/L or greater having pneumonia was related to 3 of the studied variables: age, ANC, and serum CRP level. The incidence of pneumonia increased with age (odds ratio [OR] of 2.62 for infants >12 months; 95% confidence interval [95% CI], 1.04-6.60), CRP level greater than 100 mg/L (OR, 3.18; 95% CI, 1.19-8.51), and ANC greater than 20 x 10(9)/L (OR, 3.52; 95% CI, 1.37-9.06). White blood cell count was not predictive of occult pneumonia when ANC was taken into account. CONCLUSIONS: In the era of PCV7, the incidence of pneumonia in infants younger than 36 months with high FWS and WBC count greater than 20 x 10(9)/L seems to be lower than that previously reported. However, this is not a uniform group because the incidence of pneumonia increases in infants older than 12 months and with higher ANC and serum CRP level. PMID- 20577141 TI - Glutathione S-transferase polymorphisms in osteosarcoma patients. AB - BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Multidrug resistance and poor clinical outcome are the problems that still affect osteosarcoma patients. The glutathione S-transferase supergene family includes several genes that encode enzymes involved in the detoxification of many xenobiotic agents, including carcinogens and anticancer drugs. The polymorphisms in these genes have already been associated both with cancer susceptibility and anticancer drugs resistance. OBJECTIVES: This study aims to investigate the genotype frequencies of GSTM1, GSTT1 and GSTM3 genes in 80 osteosarcoma patients and 160 normal control participants, and also the influence of these polymorphisms in the clinical outcome of osteosarcoma patients. METHODS: GSTM1 and GSTT1 deletion polymorphisms were examined through a multiplex-PCR and the GSTM3 polymorphism of three base pair-deletion at intron 6 using PCR restriction fragments length polymorphism method. RESULTS: We found that GSTM1 null genotype is correlated to poor clinical outcome characterized by the increased lung relapse occurrence [odds ratio (OR)=2.71, P=0.036], while the presence of at least one GSTM1 allele is associated with a good response to treatment and better survival (OR=4.28, P=0.020 and hazards ratio=4.09, P=0.0078, respectively). The GSTT1 null genotype was correlated with a better overall survival (hazards ratio=7.15, P=0.0247), whereas GSTM3*B allele was associated with metastasis at diagnosis (OR=2.83, P=0.028). CONCLUSION: The findings of this study suggest that GST polymorphisms may have a role in treatment response and osteosarcoma progression. PMID- 20577142 TI - The ALDH2 and DRD2/ANKK1 genes interacted in bipolar II but not bipolar I disorder. AB - AIM: Clarifying the association between bipolar I and bipolar II, the two most common subtypes of bipolar disorder, at the genetic level is essential for improving our understanding of these disorders. The dopaminergic system has been implicated in the pathogenesis of bipolar disorder. It may be important to investigate genes involved in metabolizing dopamine and encoding dopamine receptors, such as the aldehyde dehydrogenase 2 (ALDH2) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) genes. We examined the association of the ALDH2 and DRD2/ANKK1 Taq IA polymorphisms with bipolar I and II disorders and possible interactions between these genes. METHODS: Seven hundred and fifty participants were recruited: 207 with bipolar I disorder, 277 with bipolar II disorder, and 266 healthy controls. The genotypes of the ALDH2 and DRD2/ANKK1 TaqIA polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Logistic regression analysis showed a statistically significant interaction for the A1/A1 genotype of the DRD2/ANKK1 TaqIA, and the ALDH2*1*1 genotypes (P=0.009) could predict bipolar II patients compared with individuals without bipolar disorder. However, there was no association between the ALDH2 or DRD2/ANKK1 gene with neither bipolar I nor bipolar II disorder. CONCLUSION: Our findings may provide initial evidence that the ALDH2 and DRD2/ANKK1 genes interact in specific subtypes of bipolar disorders. Our findings also suggest a unique genetic distinction between bipolar I and bipolar II disorders. PMID- 20577144 TI - Influence of prophylactic probiotics and selective decontamination on bacterial translocation in patients undergoing pancreatic surgery: a randomized controlled trial. AB - Bacterial translocation (BT) is suspected to play a major role in the development of infections in surgical patients. However, the clinical association between intestinal barrier dysfunction, BT, and septic morbidity has remained unconfirmed. The objective of this study was to study BT in patients undergoing major abdominal surgery and the effects of probiotics, selective decontamination of the digestive tract (SDD), and standard treatment on intestinal barrier function. In a randomized controlled setting, 30 consecutive patients planned for elective pylorus-preserving pancreaticoduodenectomy (PPPD) were allocated to receive perioperatively probiotics, SDD, or standard treatment. To assess intestinal barrier function, intestinal fatty acid-binding protein (mucosal damage) and polyethylene glycol recovery (intestinal permeability) in urine were measured perioperatively. BT was assessed by real-time polymerase chain reaction and multiplex ligation-dependent probe amplification (MLPA) in mesenteric lymph nodes (MLNs) harvested early (baseline control) and at the end of surgery ("end of-surgery" MLNs, after 3h in PPPD patients). Polymerase chain reaction detected bacterial DNA in 18 of 27 end-of-surgery MLNs and in 13 of 23 control MLNs (P = 0.378). Probiotics and SDD had no significant effect on the number of positive MLNs or the change in bacterial DNA during operation. Multiplex ligation dependent probe amplification analysis showed significantly increased expression of only 4 of 30 inflammatory mediator-related genes in end-of-surgery compared with early sampled MLN (P < 0.05). Polyethylene glycol recovery was unaffected by operation, probiotics and SDD as compared with standard treatment. Intestinal fatty acid-binding protein levels were increased shortly postoperatively only in patients treated with SDD (P = 0.02). Probiotics and SDD did not influence BT, intestinal permeability, or inflammatory mediator expression. Bacterial translocation after abdominal surgery may be part of normal antigen-sampling processes of the gut. PMID- 20577143 TI - Systemic inflammation and liver injury following hemorrhagic shock and peripheral tissue trauma involve functional TLR9 signaling on bone marrow-derived cells and parenchymal cells. AB - Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing a nonfunctional, mutant form of TLR9, we identified a role of TLR9 in driving the initial cytokine response and liver damage in a model of hemorrhagic shock and bilateral femur fracture. Circulating DNA levels were found to correlate with the degree of tissue damage. Experiments using chimeric mice show that TLR9 on both bone marrow-derived cells and parenchymal cells are important for the TLR9-mediated liver and tissue damage, as well as systemic inflammation after HS/T. These data suggest that release of DNA may be a driver of the inflammatory response to severe injury as well as a marker of the extent of tissue damage. One of the sensors of DNA in the setting of HS/T seems to be TLR9. PMID- 20577145 TI - Macrophage-produced IL-12p70 mediates hemorrhage-induced damage in a complement dependent manner. AB - Hemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice after hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wild-type mice, CR2-fH attenuated hemorrhage-induced, midjejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, leukotriene B4, IL-12p40, and TNF-[alpha] production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pretreated with clodronate-containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage-induced midjejunal damage and inflammation. PMID- 20577146 TI - Sepsis-induced alterations in protein-protein interactions within mTOR complex 1 and the modulating effect of leucine on muscle protein synthesis. AB - Sepsis-induced muscle atrophy is produced in part by decreased protein synthesis mediated by inhibition of mTOR (mammalian target of rapamycin). The present study tests the hypothesis that alteration of specific protein-protein interactions within the mTORC1 (mTOR complex 1) contributes to the decreased mTOR activity observed after cecal ligation and puncture in rats. Sepsis decreased in vivo translational efficiency in gastrocnemius and reduced the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein (BP) 1, S6 kinase (S6K) 1, and mTOR, compared with time-matched pair-fed controls. Sepsis decreased T246 phosphorylated PRAS40 (proline-rich Akt substrate 40) and reciprocally increased S792-phosphorylated raptor (regulatory associated protein of mTOR). Despite these phosphorylation changes, sepsis did not alter PRAS40 binding to raptor. The amount of the mTOR-raptor complex did not differ between groups. In contrast, the binding and retention of both 4E-BP1 and S6K1 to raptor were increased, and, conversely, the binding of raptor with eIF3 was decreased in sepsis. These changes in mTORC1 in the basal state were associated with enhanced 5'-AMP activated kinase activity. Acute in vivo leucine stimulation increased muscle protein synthesis in control, but not septic rats. This muscle leucine resistance was associated with coordinated changes in raptor-eIF3 binding and 4E-BP1 phosphorylation. Overall, our data suggest the sepsis-induced decrease in muscle protein synthesis may be mediated by the inability of 4E-BP1 and S6K1 to be phosphorylated and released from mTORC1 as well as the decreased recruitment of eIF3 necessary for a functional 48S complex. These data provide additional mechanistic insight into the molecular mechanisms by which sepsis impairs both basal protein synthesis and the anabolic response to the nutrient signal leucine in skeletal muscle. PMID- 20577147 TI - Acute endotoxemia inhibits microvascular nitric oxide-dependent vasodilation in humans. AB - Nitric oxide (NO) is crucial for the microvascular homeostasis, but its role played in the microvascular alterations during sepsis remains controversial. We investigated NO-dependent vasodilation in the skin microcirculation and plasma levels of asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of the NO synthases, in a human model of sepsis. In this double-blind, randomized, crossover study, microvascular NO-dependent (local thermal hyperemia) and NO independent vasodilation (post-occlusive reactive hyperemia) assessed by laser Doppler imaging, plasma levels of ADMA, and l-arginine were measured in seven healthy obese volunteers, immediately before and 4 h after either a i.v. bolus injection of Escherichia coli endotoxin (LPS; 2 ng/kg) or normal saline (placebo) on two different visits at least 2 weeks apart. LPS caused the expected systemic effects, including increases in heart rate (+43%, P < 0.001), cardiac output (+16%, P < 0.01), and rectal temperature (+1.4 degrees C, P < 0.001), without change in arterial blood pressure. LPS affected neither baseline skin blood flow nor post-occlusive reactive hyperemia but decreased the NO-dependent local thermal hyperemia response, l-arginine, and, to a lesser extent, ADMA plasma levels. The changes in NO-dependent vasodilation were not correlated with the corresponding changes in the plasma levels of ADMA, l-arginine, or the l arginine/ADMA ratio. Our results show for the first time that experimental endotoxemia in humans causes a specific decrease in endothelial NO-dependent vasodilation in the microcirculation, which cannot be explained by a change in ADMA levels. Microvascular NO deficiency might be responsible for the heterogeneity of tissue perfusion observed in sepsis and could be a therapeutic target. PMID- 20577148 TI - Actinonin, a meprin A inhibitor, protects the renal microcirculation during sepsis. AB - Sepsis-induced acute kidney injury occurs in 20% to 50% of septic patients and nearly doubles the mortality rate of sepsis. Because treatment in the septic patient is usually begun only after the onset of symptoms, therapy that is effective even when delayed would have the greatest impact on patient survival. The metalloproteinase meprin A, an oligomeric complex made of alpha- and beta subunits, is highly expressed at the brush-border membranes of the kidney and capable of degrading numerous substrates including extracellular matrix proteins and cytokines. The goal of the present study was to compare the therapeutic potential of actinonin, an inhibitor of meprin A, when administered before and after the onset of sepsis. Mice were treated with actinonin at 30 min before or 7 h after induction of sepsis by cecal ligation and puncture (CLP). Intravital videomicroscopy was used to image renal peritubular capillary perfusion and reactive nitrogen species. Actinonin treatment 30 min before CLP reduced IL-1beta levels and prevented the fall in renal capillary perfusion at 7 and 18 h. Actinonin also prevented the fall in renal capillary perfusion even when administered at 7 h after CLP. In addition, even late administration of actinonin preserved renal morphology and lowered blood urea nitrogen and serum creatinine concentrations. These data suggest that agents such as actinonin should be evaluated further as possible therapeutic agents because targeting both the early systemic and later organ-damaging effects of sepsis should have the highest likelihood of success. PMID- 20577149 TI - Identification of haplotype tag SNPs within the entire TLR2 gene and their clinical relevance in patients with major trauma. AB - Toll-like receptor 2 (TLR2) signaling plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire TLR2 gene and to investigate their clinical relevance in patients with major trauma. A total of 410 patients with major trauma were prospectively recruited. The htSNPs of the TLR2 gene was determined using HapMap database and linkage disequilibrium analysis. The htSNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The whole peripheral blood samples obtained immediately after admission were stimulated with bacterial lipoprotein and then determined for production of tumor necrosis factor-alpha, interleukin 8, and interleukin 10. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were accessed. Three SNPs (rs1898830, rs3804099, and rs7656411) were identified as htSNPs for the TLR2 gene. All of them were shown to be high-frequency SNPs in this study cohort. Two of them (rs1898830 and rs3804099) and the haplotype ATT were significantly associated with cytokine production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Only rs3804099, however, was significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma. In addition, the patients with the haplotype ATT had lower sepsis morbidity rate than those without the haplotype ATT. Therefore, three SNPs might act as htSNPs for the entire TLR2 gene in the Chinese population. The rs3804099 and the haplotype ATT might be used as relevant risk estimates for the development of sepsis and MOD in patients with major trauma. PMID- 20577150 TI - The peroxynitrite catalyst WW-85 improves pulmonary function in ovine septic shock. AB - Systemic inflammatory response syndrome is associated with excessive production of nitric oxide (NO.) and superoxide (O2), forming peroxynitrite, which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the peroxynitrite decomposition catalyst, WW 85, in a sheep model of acute lung injury and septic shock. Eighteen sheep were operatively prepared and randomly allocated to the sham, control, or WW-85 group (n = 6 each). After a tracheotomy, acute lung injury was produced in the control and WW-85 groups by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30-mL suspension of live Pseudomonas aeruginosa bacteria (containing 2 - 5 * 1011 colony-forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 h and ventilated with 100% oxygen. WW-85 was administered 1 h after injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg.kg-1.h-1 until the end of the 24-h experimental period. Compared with injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase concentrations, lung malondialdehyde concentrations, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide-peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model. PMID- 20577151 TI - Streptococcal M1 protein-induced lung injury is independent of platelets in mice. AB - Streptococcus pyogenes of the M1 serotype is frequently associated with severe streptococcal infections. M1 protein challenge can cause widespread microthrombosis, suggesting a role of platelets in streptococcal sepsis. Herein, we hypothesized that platelets may play a role in M1 protein-induced lung inflammation and injury. M1 protein was injected intravenously in C57Bl/6 mice. For platelet and neutrophil depletion, an anti-GP1balpha antibody and an anti-Gr 1 antibody, respectively, were administered before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for analysis of neutrophil infiltration, edema, and macrophage inflammatory protein 2 (MIP-2) formation. Blood was collected for analysis of membrane-activated complex 1 (Mac-1) and CD40 ligand (CD40L) expression on neutrophils and platelets as well as soluble CD40L in plasma. M1 protein caused significant pulmonary damage characterized by neutrophil infiltration, increased formation of edema and MIP-2 in the lung, and enhanced Mac-1 expression on neutrophils. However, M1 protein challenge had no effect on platelet surface expression of CD40L or soluble CD40L levels in plasma. Interestingly, platelet depletion had no influence on M1 protein-induced neutrophil recruitment, MIP-2 production, and tissue damage in the lung or Mac-1 expression on neutrophils. Moreover, we observed that M1 protein could bind to neutrophils but not to platelets. On the other hand, neutrophil depletion abolished M1 protein-induced edema formation and tissue damage in the lung. Our data suggest that neutrophils but not platelets are involved in the pathophysiology of M1 protein-provoked pulmonary damage. Thus, neutrophils may constitute a key target in infections caused by S. pyogenes of the M1 serotype. PMID- 20577152 TI - Delayed resuscitation with physostigmine increases end organ damage in alcohol intoxicated rats. AB - Previous studies from our laboratory have identified a role for blunted central sympathetic activation in the acute alcohol intoxication (AAI)-induced impairment of the counterregulatory response to hemorrhagic shock (HS). Immediate fluid resuscitation (FR) with acetylcholinesterase inhibitors restores the neuroendocrine and pressor responses to FR in AAI + HS. We hypothesized this intervention would remain beneficial after delay and that restoration of mean arterial blood pressure (MABP) during FR would attenuate organ damage. Male Sprague-Dawley rats received a primed constant alcohol infusion (2.5 g . kg + 0.3 g . kg . h for 15 h) or isocaloric dextrose (DEX) before HS (40 mmHg for 60 min) and FR with lactated Ringer's (LR) solution +/- physostigmine (PHYS; 100 ug . kg) immediately or after a 60-min delay after HS. Immediate LR solution elevated MABP in DEX + HS. Acute alcohol intoxication delayed the initial MABP recovery. Delayed LR solution did not further increase MABP in DEX- or AAI + HS. LR solution + PHYS increased MABP in DEX- and AAI + HS after immediate and delayed FR. No differences were noted in markers of organ dysfunction (alanine aminotransferase [ALT], aspartate aminotransferase, blood urea nitrogen, creatinine) after DEX + HS, and this was unaltered by immediate or delayed LR solution + PHYS. Acute alcohol intoxication + HS increased ALT, which was attenuated by immediate LR solution + PHYS. In contrast, delayed LR solution + PHYS exacerbated tissue injury in AAI + HS, as reflected by increased ALT, aspartate aminotransferase, blood urea nitrogen, creatinine, and liver protein carbonylation over time-matched LR solution. In conclusion, PHYS enhanced blood pressure recovery independent of time of FR and presence of AAI. However, in AAI + HS, delayed LR solution + PHYS accentuated organ damage and dysfunction. These findings suggest that although enhancing the sympathetic response can improve hemodynamic recovery during AAI, it may compromise tissue perfusion and enhance tissue injury. PMID- 20577153 TI - Echocardiography for hemodynamic evaluation in the intensive care unit. AB - The use of echocardiography in the intensive care unit for patients in shock allows the accurate measurement of several hemodynamic variables in a noninvasive way. By using echocardiography as a hemodynamic monitoring tool, the clinician can evaluate several aspects of shock states, such as cardiac output and fluid responsiveness, myocardial contractility, intracavitary pressures, and biventricular interactions. However, to date, there have been few guidelines suggesting an objective hemodynamic-based examination in the intensive care unit, and most intensivists are usually not familiar with this tool. In this review, we describe some of the most important hemodynamic parameters that can be obtained at the bedside with transthoracic echocardiography. PMID- 20577154 TI - Expanded HIV testing and trends in diagnoses of HIV infection - District of Columbia, 2004-2008. AB - In the District of Columbia (DC), the human immunodeficiency virus (HIV) case rate is nearly 10 times the U.S. rate and higher than comparable U.S. cities, such as Baltimore, Philadelphia, New York City, Detroit, and Chicago. In June 2006, the DC Department of Health (DCDOH) began implementing CDC's 2006 recommendations for routine, voluntary HIV screening in health-care settings. To describe recent trends in HIV disease and testing, CDC and DCDOH analyzed DC HIV case surveillance data, HIV testing data, and data from the Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicated that the rate of newly diagnosed acquired immunodeficiency syndrome (AIDS) cases decreased consistently, from 164 cases per 100,000 in 2004 to 137 in 2007 and 107 in 2008. Among newly diagnosed AIDS cases, the number and rate were higher among blacks/African Americans compared with whites and Hispanics/Latinos. During 2005-2007, BRFSS results showed a significant increase in the proportion of the population that had been tested for HIV within the past 12 months, from 15% to 19%. Although the causes of the improvement in these indicators are unknown and cannot be linked to any specific intervention, they suggest improvements in the delivery of HIV testing and linkage to care services in DC. To address continuing racial disparities, DCDOH has increased HIV education and prevention efforts through enhanced collaborations, working with DC residents as spokespersons for local marketing campaigns and creating toolkits for health-care providers to expand HIV testing and linkage to care. PMID- 20577155 TI - Routine jail-based HIV testing - Rhode Island, 2000-2007. AB - The prevalence of human immunodeficiency virus (HIV) infection among incarcerated persons in the United States (1.5%) is approximately four times greater than the prevalence among persons in community settings (0.4%). In 2006, CDC recommended HIV testing in correctional facilities and elsewhere as part of routine medical evaluation. However, jail-based testing can be difficult logistically because of rapid turnover among detainees. In 2009, the Rhode Island Department of Corrections (RIDOC) reviewed its HIV testing program to assess HIV case identification, characterize HIV risk factors, and estimate the proportion of detainees who might not have been tested if testing had been delayed. RIDOC reviewed records of HIV testing of jail detainees during 2000-2007. During this period, 102,229 HIV tests were administered (representing an estimated 40,000 60,000 unique jail detainees), and HIV infection was newly diagnosed in 169 detainees, including 80 (48%) with unknown HIV risk factors. HIV testing was completed within 24 hours of jail admission. If HIV testing had been delayed for 7 days, 72 detainees (43%) would have been released before they could be tested, resulting in a delay in their HIV diagnosis and care, and continued risk for HIV transmission. To maximize case identification, all detainees should be offered voluntary HIV testing early in their incarceration as part of the first clinical evaluation, regardless of reported risk factors. PMID- 20577156 TI - Sodium intake among adults - United States, 2005-2006. AB - Excessive dietary sodium consumption increases blood pressure, which increases the risk for stroke, coronary heart disease, heart failure, and renal disease. Based on predictive modeling of the health benefits of reduced salt intake on blood pressure, a population-wide reduction in sodium of 1,200 mg/day would reduce the annual number of new cases of coronary heart disease by 60,000-120,000 cases and stroke by 32,000-66,000 cases. Dietary Guidelines for Americans 2005 recommends that specific groups, including persons with hypertension, all middle aged and older adults, and all blacks should limit intake to 1,500 mg/day of sodium. These specific groups include nearly 70% of the U.S. adult population. For all other adults, the recommended limit is <2,300 mg/day of sodium. To estimate the proportion of adults whose sodium consumption was within recommended limits, CDC analyzed data from the National Health and Nutrition Examination Survey (NHANES) for 2005-2006, the most recent data available. Estimated average sodium intake and sources of sodium and calories by food category also were analyzed. This report summarizes the results of that analysis, which determined that only 5.5% of adults in the 2 * 10(6) CD34(+) cells/kg in 1-3 leukaphereses. In all, 5/13 patients have already undergone autograft with plerixafor-mobilized PBSCs, showing a rapid and durable hematological recovery. Our results suggest that the pre-emptive addition of plerixafor to G-CSF after chemotherapy is safe and may allow the rescue of lymphoma and MM patients, who need autologous transplantation but are failing PBSC mobilization. PMID- 20577219 TI - Air-leak syndrome following allo-SCT in adult patients: report from the Kanto Study Group for Cell Therapy in Japan. AB - We retrospectively investigated air-leak syndrome (ALS), including pneumothorax and mediastinal/s.c. emphysema, following allogeneic hematopoietic SCT. Eighteen patients (1.2%) developed ALS among 1515 undergoing SCT between 1994 and 2005 at the nine hospitals participating in the Kanto Study Group on Cell Therapy. The median onset of ALS was at 575 days (range: 105-1766) after SCT and 14 patients (77.8%) had experienced late onset noninfectious pulmonary complications (LONIPC) before ALS. Chronic GVHD (cGVHD) was the strongest risk factor for ALS (odds ratio 13.5, P=0.013 by multivariate analysis). Repeat SCT, male sex and age <38 years at the time of transplantation were also significant risk factors for ALS. Patients with ALS had a significantly worse survival rate than those without ALS (61.5 vs 14.9% at 3 years; P=0.000). The main cause of death was respiratory complications in 8 of the 18 patients. In conclusion, ALS is a rare complication of SCT that is more likely to occur in relatively young male patients with cGVHD and/or LONIPC. It is possible that better understanding and treatment of LONIPC may lead to prevention of ALS. PMID- 20577220 TI - Auto-SCT in severe paraproteinemic neuropathy. PMID- 20577221 TI - Assignment of scores for the hematopoietic cell transplantation comorbidity index: integer vs exact weights. PMID- 20577222 TI - Regulatory T cell expression of CLA or alpha(4)beta(7) and skin or gut acute GVHD outcomes. AB - Regulatory T cells (Tregs) are a suppressive subset of CD4(+) T lymphocytes implicated in the prevention of acute GVHD (aGVHD) after allo-SCT (ASCT). To determine whether increased frequency of Tregs with a skin-homing (cutaneous lymphocyte Ag, CLA(+)) or a gut-homing (alpha(4)beta(7)(+)) phenotype is associated with reduced risk of skin or gut aGVHD, respectively, we quantified circulating CLA(+) or alpha(4)beta(7)(+) on Tregs at the time of neutrophil engraftment in 43 patients undergoing ASCT. Increased CLA(+) Tregs at engraftment was associated with the prevention of skin aGVHD (2.6 vs 1.7%; P=0.038 (no skin aGVHD vs skin aGVHD)), and increased frequencies of CLA(+) and alpha(4)beta(7)(+) Tregs were negatively correlated with severity of skin aGVHD (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.46-0.98; P=0.041) or gut aGVHD (OR, 0.93; 95% CI, 0.88-0.99; P=0.031), respectively. This initial report suggests that Treg tissue-homing subsets help to regulate organ-specific risk and severity of aGVHD after human ASCT. These results need to be validated in a larger, multicenter cohort. PMID- 20577223 TI - Impact of high-dose chemotherapy followed by auto-SCT for positive interim [18F] FDG-PET diffuse large B-cell lymphoma patients. AB - [(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is increasingly used for response assessment in diffuse large B-cell lymphoma (DLBCL). A positive interim FDG-PET was shown to be associated with an unfavorable outcome in high-grade non-Hodgkin's lymphomas. For positive interim FDG-PET patients, the question of increasing the intensity of treatment using high-dose chemotherapy followed by auto-SCT (HDC-ASCT) remains unanswered. We retrospectively analyzed the prognostic value of FDG-PET in 42 DLBCL patients who were systematically evaluated at time of diagnosis, before and after HDC-ASCT. Of note, HDC-ASCT was part of the initial treatment strategy, while FDG-PET results did not influence the treatment approach. Results and outcome were analyzed according to FDG-PET results before and after HDC-ASCT. Patients were classified into three groups according to FDG-PET results before and after HDC-ASCT: those who were negative before and after (-/-; n=25), positive before and negative after (+/-; n=9) or positive before and after (+/+; n=8). The median follow-up was 34.5 (range, 19-74) months. The median EFS was significantly lower for the +/+ group (27.4 months) as compared with other groups (median not reached; P=0.0001). More importantly, there was no difference in term of EFS between the /- group compared with the +/- group. These results suggest that HDC-ASCT can significantly improve the bad prognosis, otherwise indicated by a positive interim FDG-PET. PMID- 20577224 TI - The G protein beta3 subunit C825T polymorphism is associated with microalbuminuria in hypertensive women and cardiovascular disease in hypertensive men. AB - BACKGROUND: The aim of the study was to examine the association between the G protein beta3 subunit C825T polymorphism, associated with cardiovascular risk factors like hypertension (HT) and obesity and microalbuminuria (MA), reflecting the endothelial dysfunction in the atherosclerotic process. Second, we wanted to examine the association between the polymorphism and cardiovascular disease (CVD). METHODS: In the large population-based, cross-sectional Nord-Trondelag Health Study, HUNT 1995-1997, a total of 5,755 treated hypertensive individuals attended the MA substudy. A randomly selected sample of 1,000 of these was genotyped. A total of 402 men and 540 women were included in the final analyses. MA was measured as albumin/creatinine ratio (ACR) in three urine samples. Logistic regression was used to calculate odds ratios (ORs) for the association between MA or CVD and the genotype. RESULTS: The study demonstrated a positive association between the TT genotype and MA in women (OR 3.2, 95% confidence interval (CI): 1.1-8.7, P = 0.03), but not in men. The association became stronger with increasing number of positive urine samples and with increasing cutoff value in women with TT genotype compared to the CC genotype. Additionally, there was a positive association between TT genotype and CVD in men and postmenopausal women without hormone therapy. CONCLUSIONS: Increased MA in TT homozygous women might be explained by other mechanisms of albuminuria or inflammation than the atherosclerotic process. We postulate that the association between CVD and the genotype are mediated through mechanisms other than the classical risk factors and endothelial dysfunction, reflected by MA, which have to be further investigated. PMID- 20577225 TI - Efficacy of alpha-lactalbumin and milk protein on weight loss and body composition during energy restriction. AB - Our objective was to examine whether elevated alpha-lactalbumin (alphalac) protein intake compared to elevated supra sustained milk protein (SSP) and sustained milk protein (SP) intake results into a difference in body weight and body composition over a 6-month energy-restriction intervention. Body weight, body composition, resting energy expenditure (REE), satiety and blood- and urine parameters of 87 subjects (BMI 31 +/- 5 kg/m(2) and fat percentage 40 +/- 8%) were assessed before and after daily energy intakes of 100, 33, and 67% for 1, 1, and 2 months respectively (periods 1, 2, and 3), with protein intake from meal replacements and 2 months of 67% with ad libitum protein intake additional to the meal replacements (period 4). The diets resulted in 0.8 +/- 0.3 g/kg body mass (BM) for SP and significant higher protein intake (24-h nitrogen) of 1.2 +/- 0.3 and 1.0 +/- 0.3 g/kgBM for SSP and alphalac (P < 0.05). Body weight and fat percentage was decreased in all groups after 6 months (SP -7 +/- 5 kg and -5 +/- 3%; SSP -6 +/- 3 kg and -5 +/- 3%; alphalac -6 +/- 4 kg and -4 +/- 4%, P < 0.001; there was no significant group by time difference). Furthermore, sparing of fat free mass (FFM) and preservation of REE in function of FFM during weight loss was not significantly different between the alphalac-group and the SSP- and SP groups. In conclusion, the efficacy of alphalac in reduction of body weight and fat mass (FM), and preservation of FFM does not differ from the efficacy of similar daily intakes of milk protein during 6 months of energy restriction. PMID- 20577226 TI - Research and the axe-factor. PMID- 20577227 TI - Mobile dental care. PMID- 20577228 TI - DCP coalition. PMID- 20577229 TI - AVM management. PMID- 20577230 TI - Putty technique. PMID- 20577231 TI - Oral systemic interfaces. PMID- 20577232 TI - Unfair summary. PMID- 20577234 TI - International dental elite attend John McLean Symposium. PMID- 20577236 TI - NHS Bristol launches free iPhone app. PMID- 20577237 TI - Dental X-rays may increase thyroid cancer risk. PMID- 20577261 TI - Sustained calcium signalling and caspase-3 activation involve NMDA receptors in thymocytes in contact with dendritic cells. AB - L-glutamate, the major excitatory neurotransmitter, also has a role in non neuronal tissues and modulates immune responses. Whether NMDA receptor (NMDAR) signalling is involved in T-cell development is unknown. In this study, we show that mouse thymocytes expressed an array of glutamate receptors, including NMDARs subunits. Sustained calcium (Ca(2+)) signals and caspase-3 activation in thymocytes were induced by interaction with antigen-pulsed dendritic cells (DCs) and were inhibited by NMDAR antagonists MK801 and memantine. NMDARs were transiently activated, triggered the sustained Ca(2+) signal and were corecruited with the PDZ-domain adaptor postsynaptic density (PSD)-95 to thymocyte-DC contact zones. Although T-cell receptor (TCR) activation was sufficient for relocalization of NMDAR and PSD-95 at the contact zone, NMDAR could be activated only in a synaptic context. In these T-DC contacts, thymocyte activation occurred in the absence of exogenous glutamate, indicating that DCs could be a physiological source of glutamate. DCs expressed glutamate, glutamate-specific vesicular glutamate transporters and were capable of fast glutamate release through a Ca(2+)-dependent mechanism. We suggest that glutamate released by DCs could elicit focal responses through NMDAR-signalling in T cells undergoing apoptosis. Thus, synapses between T and DCs could provide a functional platform for coupling TCR activation and NMDAR signalling, which might reflect on T-cell development and modulation of the immune response. PMID- 20577262 TI - A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum. AB - A natural BH3-mimetic, small-molecule inhibitor of Bcl-2, (-)-gossypol, shows promise in ongoing phase II and III clinical trials for human prostate cancer. In this study we show that (-)-gossypol preferentially induces autophagy in androgen independent (AI) prostate cancer cells that have high levels of Bcl-2 and are resistant to apoptosis, both in vitro and in vivo, but not in androgen-dependent (AD) cells with low Bcl-2 and sensitive to apoptosis. The Bcl-2 inhibitor induces autophagy through blocking Bcl-2-Beclin1 interaction, together with downregulating Bcl-2, upregulating Beclin1, and activating the autophagic pathway. The (-)-gossypol-induced autophagy is dependent on Beclin1 and Atg5. Our results show for the first time that (-)-gossypol can also interrupt the interactions between Beclin1 and Bcl-2/Bcl-xL at endoplasmic reticulum, thus releasing the BH3-only pro-autophagic protein Beclin1, which in turn triggers the autophagic cascade. Oral administration of (-)-gossypol significantly inhibited the growth of AI prostate cancer xenografts, representing a promising new regimen for the treatment of human hormone-refractory prostate cancer with Bcl-2 overexpression. Our data provide new insights into the mode of cell death induced by Bcl-2 inhibitors, which will facilitate the rational design of clinical trials by selecting patients who are most likely to benefit from the Bcl-2-targeted molecular therapy. PMID- 20577264 TI - Polo-like kinase 1 phosphorylation of G2 and S-phase-expressed 1 protein is essential for p53 inactivation during G2 checkpoint recovery. AB - In response to G2 DNA damage, the p53 pathway is activated to lead to cell-cycle arrest, but how p53 is eliminated during the subsequent recovery process is poorly understood. It has been established that Polo-like kinase 1 (Plk1) controls G2 DNA-damage recovery. However, whether Plk1 activity contributes to p53 inactivation during this process is unknown. In this study, we show that G2 and S-phase-expressed 1 (GTSE1) protein, a negative regulator of p53, is required for G2 checkpoint recovery and that Plk1 phosphorylation of GTSE1 at Ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery. PMID- 20577263 TI - SIRT1 stabilizes PML promoting its sumoylation. AB - SIRT1, the closest mammalian homolog of yeast Sir2, is an NAD(+)-dependent deacetylase with relevant functions in cancer, aging, and metabolism among other processes. SIRT1 has a diffuse nuclear localization but is recruited to the PML nuclear bodies (PML-NBs) after PML upregulation. However, the functions of SIRT1 in the PML-NBs are unknown. In this study we show that primary mouse embryo fibroblasts lacking SIRT1 contain reduced PML protein levels that are increased after reintroduction of SIRT1. In addition, overexpression of SIRT1 in HEK-293 cells increases the amount of PML protein whereas knockdown of SIRT1 reduces the size and number of PML-NBs and the levels of PML protein in HeLa cells. SIRT1 stimulates PML sumoylation in vitro and in vivo in a deacetylase-independent manner. Importantly, the absence of SIRT1 reduces the apoptotic response of vesicular stomatitis virus-infected cells and favors the extent of this PML sensitive virus replication. These results show a novel function of SIRT1 in the control of PML and PML-NBs. PMID- 20577265 TI - CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells. AB - Telomere shortening limits the proliferation of primary human fibroblasts by the induction of senescence, which is mediated by ataxia telangiectasia mutated dependent activation of p53. Here, we show that CHK2 deletion impairs the induction of senescence in mouse and human fibroblasts. By contrast, CHK2 deletion did not improve the stem-cell function, organ maintenance and lifespan of telomere dysfunctional mice and did not prevent the induction of p53/p21, apoptosis and cell-cycle arrest in telomere dysfunctional progenitor cells. Together, these results indicate that CHK2 mediates the induction of senescence in fibroblasts, but is dispensable for the induction of telomere dysfunction checkpoints at the stem and progenitor cell level in vivo. PMID- 20577266 TI - Agomelatine, the first melatonergic antidepressant: discovery, characterization and development. AB - Current management of major depression, a common and debilitating disorder with a high social and personal cost, is far from satisfactory. All available antidepressants act through monoaminergic mechanisms, so there is considerable interest in novel non-monoaminergic approaches for potentially improved treatment. One such strategy involves targeting melatonergic receptors, as melatonin has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed states. This article describes the discovery and development of agomelatine, which possesses both melatonergic agonist and complementary 5-hydroxytryptamine 2C (5-HT2C) antagonist properties. Following comprehensive pharmacological evaluation and extensive clinical trials, agomelatine (Valdoxan/Thymanax; Servier) was granted marketing authorization in 2009 for the treatment of major depression in Europe, thereby becoming the first approved antidepressant to incorporate a non-monoaminergic mechanism of action. PMID- 20577267 TI - Immune cell crosstalk in type 1 diabetes. AB - The development of type 1 diabetes involves a complex interaction between pancreatic beta-cells and cells of both the innate and adaptive immune systems. Analyses of the interactions between natural killer (NK) cells, NKT cells, different dendritic cell populations and T cells have highlighted how these different cell populations can influence the onset of autoimmunity. There is evidence that infection can have either a potentiating or inhibitory role in the development of type 1 diabetes. Interactions between pathogens and cells of the innate immune system, and how this can influence whether T cell activation or tolerance occurs, have been under close scrutiny in recent years. This Review focuses on the nature of this crosstalk between the innate and the adaptive immune responses and how pathogens influence the process. PMID- 20577270 TI - Screening children with NF1 for optic pathway glioma--No. PMID- 20577268 TI - Immunity and immunopathology to viruses: what decides the outcome? AB - Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and several factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins, as well as the presence of concurrent infections and past exposure to cross-reactive agents. PMID- 20577271 TI - Effect of lyophilization on the in vitro biological activity of bevacizumab. PMID- 20577269 TI - Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design. AB - One of the main challenges of developing an HIV-1 vaccine lies in eliciting immune responses that can overcome the antigenic variability exhibited by HIV. Most HIV-1 vaccine development has focused on inducing immunity to conserved regions of the HIV-1 envelope. However, new studies of the sequence-variable regions of the HIV-1 gp120 envelope glycoprotein have shown that there are conserved immunological and structural features in these regions. Recombinant immunogens that include these features may provide the means to address the antigenic diversity of HIV-1 and induce protective antibodies that can prevent infection with HIV-1. PMID- 20577272 TI - Efficacy of medical therapy in the initial management of acute primary angle closure in Asians. AB - PURPOSE: Recent studies have advocated the use of laser iridoplasty or paracentesis in the initial management of patients with acute primary angle closure (APAC). The aim of this study was to ascertain the effectiveness of medical treatment consisting of topical and systemic intraocular pressure (IOP) lowering agents in the initial management of APAC. METHODS: This was an observational case series of consecutive patients presenting with APAC at a Singapore hospital over 2 years. On diagnosis, all subjects received intravenous acetazolamide followed by oral acetazolamide, topical pilocarpine, timolol, and steroid eye drops. Resolution of APAC was defined as IOP <21 mm Hg with no acute symptoms. RESULTS: In all, 134 consecutive APAC subjects were studied. The majority of subjects were Chinese (96.3%) and female (80%), and the mean age was 63.7+/-9.6 years. The mean presenting IOP was 58+/-12.7 mm Hg and mean duration of symptoms was 2.8+/-3.2 days. With medical therapy, APAC attacks resolved within 3, 6, 12, and 24 h in 28 (21.5%), 58 (44.6%), 99 (76.2%), and 116 (89.2%) subjects, respectively. After resolution of APAC, laser iridotomy was performed in 81.6% of the subjects; 16.2% of the subjects underwent cataract extraction. There was failure of resolution of APAC in only 3 subjects (2.2%). No subject suffered any serious side effects as a result of treatment. CONCLUSIONS: Medical therapy resulted in resolution of APAC within 12 h in 76.2% of the subjects and within 24 h in 89.2% of the subjects, showing the effectiveness of medical therapy in the initial management of APAC. PMID- 20577273 TI - A randomised prospective double-masked exploratory study comparing combination photodynamic treatment and intravitreal ranibizumab vs intravitreal ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration. AB - AIMS: The aim of this study is to evaluate the effect of standard-fluence verteporfin photodynamic therapy (PDT) delivered on the first day of a ranibizumab regimen for choroidal neovascularisation secondary to age-related macular degeneration compared with ranibizumab monotherapy. METHODS: Patients were randomised to sham or standard-fluence verteporfin PDT at baseline. The first of three monthly loading doses of ranibizumab was given on the same day, and thereafter patients received monthly treatment with ranibizumab as required. All patients underwent monthly visual acuity and OCT assessment and 3-monthly fluorescein angiography with follow-up to 1 year. RESULTS: In all, 18 patients were recruited. The PDT group gained a mean of 2.2 ETDRS letters at 1 year and the sham group gained a mean of 4.4 letters (P=0.47). Both groups required a mean of 1.3 injections of ranibizumab following the 3-month loading phase. Fluorescein angiography at 1 month demonstrated marked choroidal hypoperfusion in all patients treated with PDT with reduced choroidal perfusion persisting to month 12. This did not occur in the sham group. CONCLUSION: The addition of standard fluence verteporfin PDT at baseline to a ranibizumab regimen conferred no benefit in terms of visual acuity or number of ranibizumab injections required at 1 year. The combination of these treatments resulted in persistent reduced choroidal perfusion, which raises potential safety concerns. PMID- 20577274 TI - Attitudes of patients and relatives/carers towards genetic testing for inherited retinal disease. PMID- 20577275 TI - Screening children with NF1 for optic pathway glioma--Yes. PMID- 20577277 TI - Periodontal treatment did not prevent complications of pregnancy. Evidence-based Dentistry 2010; 11: 18-19. PMID- 20577278 TI - How long do multirooted teeth with furcation involvement survive with treatment? AB - DATA SOURCES: A Medline search and handsearching of the following journals were carried out: International Journal of Periodontics and Restorative Dentistry, Journal of Clinical Periodontology, Journal of Periodontal Research and Journal of Periodontology as well as reference lists of publications selected. STUDY SELECTION: To be eligible for inclusion in this review, studies had to be longitudinal in nature. Prospective and retrospective cohort studies were considered. Studies were screened and quality assessed independently by two reviewers. Review articles, case reports and studies of fewer than 5-years' duration were excluded, as were those not providing information on tooth survival or furcation involvement. DATA EXTRACTION AND SYNTHESIS: Data was abstracted independently by two reviewers. Owing to the heterogeneity of the data, a meta analysis could not be performed. A qualitative synthesis was conducted grouping the studies into the following areas: nonsurgical furcation therapy; surgical therapy not involving tooth structures; tunnelling surgical resective therapy (eg, root resection and/ or root separation); and guided tissue regeneration (GTR) and grafting procedures. RESULTS: Twenty-two publications met the inclusion criteria. The survival rate of molars treated nonsurgically was >90% after 5-9 years. The corresponding values for the different surgical procedures were: surgical therapy, 43.1-96% (observation period, 5-53 years); tunnelling procedures, 42.9-92.9% (observation period, 5-8 years); surgical resective procedures including amputation(s) and hemisections, 62-100% (observation period, 5-13 years); and GTR, 83.3-100% (observation period, 5-12 years). The most frequent complications included caries in the furcation area after tunnelling procedures and root fractures after root-resective procedures. CONCLUSIONS: Good long-term survival rates (up to 100%) of multirooted teeth with furcation involvement were obtained following various therapeutic approaches. Initial furcation involvement (degree I) could be successfully managed by nonsurgical mechanical debridement. Vertical root fractures and endodontic failures were the most frequent complications observed following resective procedures. PMID- 20577279 TI - Multifaceted strategy needed to improve dentists' adherence to evidence-based guidelines. AB - DESIGN: This was a cluster-randomised clinical trial (RCT) of incomplete block design. INTERVENTION: The interventions comprised an online 'patient-simulated clinical case' assessment, guideline dissemination, an interactive educational meeting, and flow chart reminders. All participants received feedback on individual as well as group scores for the patient-simulated clinical case assessment. Reminders with particular information and guideline-algorithm flow diagrams were provided 2 months before post-intervention measurements. OUTCOME MEASURE: The primary outcome measure was guideline-adherent recall interval assignment, and the secondary outcome measure was guideline-adherent bitewing frequency prescription. RESULTS: For low-risk patients, guideline-adherent recall increased in the intervention group (+8%), which differed from the control group (-6.1%; P 0.01). Guideline-adherent bitewings showed mixed results. CONCLUSIONS: Multifaceted intervention had a moderate but relevant effect on the performance of general dental practitioners, which is consistent with other findings in primary care. PMID- 20577280 TI - Influencing patients' oral hygiene behaviour. AB - DESIGN: A patient-randomised controlled trial (RCT) and a cluster RCT of the same intervention were conducted independently of each other. INTERVENTION: The evidence-based intervention (a powered toothbrush and behavioural advice on timing, method and duration of toothbrushing) was framed to target oral hygiene self-efficacy (Social Cognitive Theory) and action plans (Implementation Intention Theory) to influence oral hygiene behaviour and therefore clinical outcomes. The content and the delivery of the intervention were standardised as a series of steps-altogether taking approximately 5 min. The control groups received routine care, even if that included oral hygiene advice. OUTCOME MEASURE: The primary outcome measures were behavioural (timing, duration and method of toothbrushing) matching the advice given in the intervention. Secondary outcomes were cognitive measures of self-efficacy and planning, and clinical measures of plaque and gingival bleeding. RESULTS: The study included 87 dental practices and 778 patients (patient RCT, 37 dentists and 300 patients; cluster RCT, 50 dentists and 478 patients). Controlled for baseline differences, pooled results showed that trial participants who experienced the intervention had better behavioural (timing, duration, method), cognitive (confidence, planning), and clinical (plaque, gingival bleeding) outcomes. Clinical outcomes were only significantly better in the cluster RCT, however. CONCLUSIONS: A simple, theory based intervention delivered within the constraints of a primary care environment was more effective than routine care in influencing patients' oral hygiene cognitions, behaviour and health. As clinical outcomes were significantly better only in the cluster RCT, the impact of trial design on results needs to be further explored. PMID- 20577281 TI - The best treatment for avulsed permanent teeth. AB - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, Cochrane CENTRAL, Medline and Embase were consulted, along with the websites www.clinicaltrials.gov and www.controlled-trials.com and reference lists of identified articles. There were no language restrictions. STUDY SELECTION: Only randomised controlled trials that included a minimum followup period of 12 months for interventions dealing with avulsed and replanted permanent teeth were considered. DATA EXTRACTION AND SYNTHESIS: Two review authors independently extracted data and assessed trial quality and the risk of bias in studies to be included. RESULTS: Three studies (involving, in total, 162 patients and 231 teeth) were included. Study one (high risk of bias) investigated the effect of extra-oral endodontics. This showed no significant difference in radiographic resorption compared with intra-oral endodontics provided at week 1 for teeth avulsed for longer than 60 min dry time. Study two (moderate risk of bias) investigated a 10-min soaking in thymosin alpha 1 prior to replantation and then its further use as a daily gingival injection for the first 7 days. They reported a strong benefit at 48 months (14% with periodontal healing in the control group versus 77% for the experimental group). Study three (high risk of bias) investigated a 20-min soaking with gentamycin sulphate for both groups prior to replantation and then the use of hyperbaric oxygen daily in the experimental group for 80 min for the first 10 days. They reported a strong benefit at 12 months (43% periodontal healing versus 88% for the experimental group). There was no formal reporting of adverse events. CONCLUSIONS: The available evidence suggests that extra-oral endodontic treatment is not detrimental for teeth replanted after more than 60 min dry time. Studies with moderate/ high risk of bias indicate that soaking in thymosin alpha 1 and gentamycin sulphate followed by hyperbaric oxygen may be advantageous but these strategies have not previously been reported as interventions for avulsed teeth and await further validation. More evidence with low risk of bias is required and, with the low incidence of avulsed teeth, collaborative multicentre trials are indicated. PMID- 20577282 TI - Treatment of ankylosed permanent teeth. AB - DATA SOURCES: The Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase and LILACS . There were no language restrictions. STUDY SELECTION: Randomised controlled trials (RCT) were considered that compared any intervention for treating displaced ankylosed permanent front teeth in individuals of any age. DATA EXTRACTION AND SYNTHESIS: Two independent review authors screened studies in duplicate. Although no studies were ultimately included, the authors had planned to extract data independently and to assess risk of bias following Cochrane Collaboration methods. RESULTS: The search retrieved 77 references to studies. None matched the inclusion criteria and therefore were excluded. CONCLUSIONS: There is no evidence from RCT about the comparative effectiveness of the different treatment options for ankylosed permanent front teeth. The lack of high-level evidence for the management of this health problem emphasises the need for well-designed clinical trials. PMID- 20577283 TI - Enamel matrix derivative for direct pulp capping. AB - DESIGN: A split-mouth randomised controlled trial (RCT) was conducted. INTERVENTION: Standard noncarious pulp exposures were treated with either enamel matrix derivative (EMD) or calcium hydroxide and restored with a preformed metal crown (PMC). Patients were followed up at 1, 6 and 12 months. OUTCOME MEASURE: The appearance of any of the following was considered to signify treatment failure: internal dentin resorption, spontaneous pain, gingival abscess (sinus tract), external root resorption, or pathologic mobility. RESULTS: In total, 90 direct pulp capping (DPC) treatments were performed (45 in the experimental group and 45 in the control group) and followed for 12 months. There were 88 successful treatments at the end of this period, with only two failures (one in each study group). CONCLUSIONS: Both capping materials showed a similar effectiveness in this pulp procedure with a postoperative observation time of 12 months. On the basis of this study, we recommend the use of DCP treatment on primary molars as a standard technique. PMID- 20577284 TI - Predicting successful outcomes of complete denture therapy. AB - DATA SOURCES: Ovid databases searched for relevant material for the review. STUDY SELECTION: Studies were limited to the English language and all identified articles were included. DATA EXTRACTION AND SYNTHESIS: A narrative review was conducted. RESULTS: Three RCT were identified that related directly to conventional dentures. Nineteen clinical experimental studies and seven nonexperimental clinical studies were therefore also included because of the lack of higher ranking studies in this area. All studies that were identified have been included within this review. CONCLUSIONS: There remains a paucity of research in this area. From the best available data, construction of technically correct dentures, a well-formed mandibular ridge and accuracy of jaw relations are positive indicators for success. Patient neuroticism and a poorly formed mandibular ridge are negative indicators for success. Other prognostic indicators have not been shown to be of significant value. There exists a minority of patients who will never adapt to any conventional complete denture. This problem is more acute in the mandible than the maxilla. There is need for further research in this area. PMID- 20577285 TI - Implant-supported cantilevered fixed partial dentures. AB - DATA SOURCES: Medline was used to search for relevant material for the review. STUDY SELECTION: Systematic reviews and longitudinal prospective/ retrospective studies (randomised controlled trials, controlled clinical trials and cohort studies) were chosen that reported outcomes following treatment with implant supported fixed partial denture prostheses (FPDP) with cantilever extensions, after a mean function time of at least 5 years. Two independent reviewers preformed screening and data abstraction. DATA EXTRACTION AND SYNTHESIS: Five year survival and technical complication rates were extracted, which included: loss of prosthesis, loss of implants, complications with supra-construction (fractures or deformations of the framework or veneers, loss of retention and screw or abutment loosening) and marginal bone loss. Data from included studies were pooled and summarised as a weighted mean. Disagreement regarding data extraction was resolved by discussion and consensus. RESULTS: Only three studies met the inclusion criteria for final analysis. Two of the studies had a prospective or retrospective case-control design, whereas the third was a prospective cohort study. The 5-year survival rate of cantilever FPDP varied between 89.9 and 92.7% (weighted mean, 91.9%), with implant fracture as the main cause for failure. The corresponding survival rate for FPDP without cantilever extensions was 95.3 to 96.2% (weighted mean, 95.8%). Technical complications related to the supra-construction in the three included studies were reported to occur at a frequency of 13-26% (weighted mean, 20.3%) for cantilever FPDP, compared with 0-12% (weighted mean, 9.7%) for noncantilever FPDP. The most common complications were minor porcelain fractures and bridge-screw loosening. For cantilever FPDP, the 5-year event-free survival rate varied between 66.7 and 79.2% (weighted mean, 71.7%) and between 83.1 and 96.3% (weighted mean, 85.9%) for noncantilever FPDP. No statistically significant differences were reported with regard to peri-implant bone-level change between the two prosthetic groups, either at the prosthesis or at the implant level. CONCLUSIONS: Data on implant supported FPDP with cantilever extensions are limited and therefore survival and complication rates should be interpreted with caution. The incorporation of cantilevers into implant-borne prostheses may be associated with a higher incidence of minor technical complications. PMID- 20577286 TI - Survival rates of short-span implant-supported cantilever fixed dental prostheses. AB - DATA SOURCES: Publications were sought using Medline, and searches were made by hand of the journals Clinical Oral Implants Research, International Journal of Periodontics and Restorative Dentistry, Journal of Periodontology, Journal of Clinical Periodontology and the International Journal of Oral and Maxillofacial Implants, along with reference lists of identified articles. STUDY SELECTION: Titles and abstracts were initially screened by two independent reviewers to identify prospective or retrospective longitudinal cohort studies or controlled studies reporting on implant-supported cantilever fixed dental prostheses (ICFDP) with a mean followup period of at least 5 years. A clinical examination had to be performed at the end of the followup. For multiple publications reporting on the same population, only the most recent report was included. DATA EXTRACTION AND SYNTHESIS: Data for the meta-analysis were extracted by two independent reviewers. Information regarding survival and complication rates of both implants and ICFDP were extracted. Implant survival was considered if the implant was present at the followup examination; ICFDP survival was considered if the prosthesis was present at the followup visit without any modifications. Peri implantitis and soft tissue complications were included in the category of biological complications. As for technical complications, all the events affecting the implant and/ or the meso- and/ or the suprastructures' integrity were considered. Among them, the following categories were defined: implant fractures, veneer fractures, framework fractures, abutment or screw fractures, loss of retention and screw loosening. RESULTS: The five studies included in the meta-analysis yielded an estimated 5- and 10-year ICFDP cumulative survival rate of 94.3% [95% confidence interval (CI), 84.1-98%] and 88.9% (95% CI, 70.8- 96.1%), respectively. Five-year estimates for peri-implantitis were 5.4% (95% CI, 2.0-14.2%) and 9.4% (95% CI, 3.3-25.4%) at implant and prosthesis levels, respectively. Veneer fracture (5-year estimate; 10.3%; 95% CI, 3.9-26.6%) and screw loosening (5-year estimate, 8.2%; 95% CI, 3.9-17.0%) represented the most common complications, followed by loss of retention (5-year estimate, 5.7%; 95% CI,1.9-16.5%) and abutment/ screw fracture (5-year estimate, 2.1%; 95%CI, 0.9 5.1%). Implant fracture was rare (5-year estimate, 1.3%; 95% CI, 0.2-8.3%); no framework fracture was reported. Radiographic bone level changes did not yield statistically significant differences either at the prosthesis or at the implant levels when comparing ICFDP with short-span implant-supported end-abutment fixed dental prostheses. CONCLUSIONS: ICFDP represent a predictable and reliable treatment for the replacement of posterior missing teeth in partially edentulous patients. The most frequent technical complications included veneer fractures, followed by screw loosening and loss of retention. No detrimental effects on bone levels were observed around implants in the proximity of cantilever extensions. To date, however, evidence is still sparse on the effects of various prosthetic designs (eg, distal or mesial cantilever extension), number of implants supporting ICFDP and occlusal concepts on the incidence of complications in ICFDP. PMID- 20577287 TI - Patients undergoing craniofacial tumour ablation surgery may benefit from having the implants placed simultaneously instead of waiting. AB - DATA SOURCES: Medline, Embase and the Cochrane Library were searched for studies and the reference lists of the full-text articles were checked for any additional studies. STUDY SELECTION: Included studies were randomised clinical trials (RCT) and non-RCT, cohort studies, case-control studies, case reports, or reviews that addressed the placement of dental implants at the same time as primary oncological resection in people suffering from cancer of the head and neck (primary implant insertion); or addressed benign or malignant tumours and the placement of implants into the native maxilla, mandible and zygoma, and grafted tissue. Articles were restricted to those written in English. The title and abstracts were reviewed independently by two reviewers. DATA EXTRACTION AND SYNTHESIS: Data extraction was conducted independently and a qualitative synthesis of the data presented. RESULTS: Three case reports, 13 reviews, and 25 clinical studies were selected. Eight of the clinical studies referred solely to the insertion of dental implants at the time of primary oncological resection, and only two were of a prospective design. CONCLUSIONS: Published studies concerning primary dental implants were concisely summarised, so that the collected evidence base surrounding this approach to oral rehabilitation could inform head and neck cancer teams, particularly oncological surgeons, restorative dentists, and maxillofacial prosthodontists. PMID- 20577288 TI - Surgical or nonsurgical treatment for teeth with existing root filings? AB - DATA SOURCES: Data was sought using Medline and the Cochrane Library, and relevant chapters from three major endodontic texts were consulted: Principles and Practice of Endodontics (4th Edn; editors; Torabinejad and Walton; 2008); Pathways of the Pulp (9th edition; editors, Cohen and Hargreaves; 2006), and Endodontics (6th edition; editors, Ingle, Bakland and Baumgartner; 2008). Every issue was also searched of the most recent 2 years of the following major endodontic journals: International Endodontic Journal; Journal of Endodontics; and Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology along with the reference lists of identified articles. STUDY SELECTION: Articles were included from peer-reviewed journals if they were published in English, and reported clinical and/or radiographic outcome data for nonsurgical endodontic retreatment or for endodontic surgery, with followup data for a minimum of 25 teeth and a minimum 2-year mean followup period. Studies reporting outcomes based on individual roots as opposed to whole teeth, or that did not report clinical or radiographic outcomes, which were animal studies, or studies that reported histological data only, were excluded. DATA EXTRACTION AND SYNTHESIS: When necessary, the reviewers recalculated success and failure rates when they were not directly provided in papers' tables or in the text, or when only particular data subsets met the inclusion criteria. To facilitate meta-analysis, the data were standardised according to a commonly applied classification system used to assess outcomes for nonsurgical retreatment and surgical endodontics: (1) Complete healing; (2) Incomplete healing; (3) Uncertain healing; and (4) Unsatisfactory healing (failures). When uncertainty existed regarding which of the above four categories correlated with those reported in a given article, the data were assigned to the lower healing category. For this review, success was defined as teeth categorised as showing complete healing or incomplete healing. Weighted success rates, pooled success rates, and 95% confidence interval (CI) estimates of outcomes were generated in the metaanalysis from compiled data from the included studies by using the DerSimonian-Laird random effects pooling method. RESULTS: Twenty-six endodontic surgery and eight nonsurgical retreatment articles were included. There were only four randomised controlled trials (one in the nonsurgical retreatment, and three in the endodontic surgery group). A significantly higher success rate was found for endodontic surgery at 2-4 years (77.8%) than for nonsurgical retreatment for the same followup period (70.9%; P <0.05). At 4-6 years, however, this relationship was reversed, with nonsurgical retreatment showing a higher success rate of 83.0%, compared with 71.8% for endodontic surgery (P <0.05). Insufficient numbers of articles were available to make comparisons after 6 years of followup. Endodontic surgery studies showed a statistically significant decrease in success with each increasing followup interval (P <0.05). The weighted success for 2-4 years was 77.8%, which declined at 4-6 years to 71.8% and further declined at >6 years to 62.9% (P <0.05). Conversely, the nonsurgical retreatment success rates demonstrated a statistically significant increase in weighted success at 2-4 years (70.9%) versus 4-6 years (83.0%; P <0.05). CONCLUSIONS: On the basis of these results it appears that endodontic surgery offers more favourable initial success, but nonsurgical retreatment offers a more favourable long-term outcome. PMID- 20577289 TI - Drug treatment for oral submucous fibrosis. AB - DATA SOURCES: Searches were made for relevant data using Medline and the International Poster Journal of Dentistry and Oral Medicine online database (see ipj.quintessenz.de). STUDY SELECTION: Meta-analyses, randomised controlled trials (RCT), clinical trials and other experimental designs were considered. DATA EXTRACTION AND SYNTHESIS: Because of heterogeneity of study designs and drugs used, a qualitative synthesis was conducted. RESULTS: Seventeen publications were identified of which 15 were included. Of these, six were RCT, four were clinical trials/ controlled clinical trials, and five were other types experimental studies. The studies in total involved 1224 patients. The rate of those lost to followup reached 30% in some studies. The drugs used to treat oral submucous fibrosis (OSF) were categorised into steroids, enzymes, cardiovascular drugs, antioxidants, vitamins and microelements. CONCLUSIONS: There are few high-quality studies available and the present drug treatments are in general empirical and treat only symptoms. There is a need for high-quality RCT in this area, especially studies involving combined and sequential therapy. PMID- 20577290 TI - Socioeconomic status and head and neck cancer. AB - DESIGN: This was a population-based case-control study. CASE-CONTROL SELECTION: Eligible patients were aged between 18 and 80 years and had a primary histopathological diagnosis made between April 2002 and December 2004. Diagnosis included malignant cancers of the oral cavity, oropharynx, hypopharynx or larynx. Incident cases were identified through weekly monitoring of head and neck cancer clinics in hospital departments and were confirmed by pathology department records. Controls matched by age (5-year age band) and sex were randomly selected from the lists of general practitioners. DATA ANALYSIS: Information about occupation, education, smoking and alcohol consumption was collected at personal interview. Socioeconomic circumstances were measured at an individual level (education, occupational social class, unemployment), and by area-based measures of deprivation. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed by unconditional logistic regression and were adjusted for age and sex. This model was repeated to assess for potential independent effects of the range of socioeconomic components after adjusting for smoking and alcohol consumption. Interactions between smoking and consumption of alcohol, and between individual and area-based measures for socioeconomic factors were tested by the likelihood ratio test. In addition, the most important behavioural risk factors and socioeconomic variables were entered into a stepwise multivariate logistic regression model. All statistical analyses were carried out using Statistical Analysis System (SAS; Cary, North Carolina, USA) software. RESULTS: The study population included 103 cancer patients (38 women and 65 men), and 91 controls (39 women and 52 men). Individuals living in the most deprived areas (OR, 4.66; 95% CI, 1.79- 12.18) and those who were unemployed (OR, 2.27; 95% CI, 1.21- 4.26) had a significantly higher risk of cancer than people who had high levels of educational attainment (OR, 0.17; 95% CI, 0.05-0.58). Significance was lost for all measures of social class when adjustments were made for smoking and consumption of alcohol. When the most important behavioural and socioeconomic factors were combined in a fully adjusted multivariate analysis, smoking was the only significant risk factor (OR, 15.53; 95% CI, 5.36-44.99) found to be independently associated with head and neck cancers. CONCLUSIONS: A high risk of head and neck cancer was consistently associated with poor socioeconomic circumstances. There were strong links for specific components but smoking dominated the overall profile of risk. More detailed research into the nature of such associations is needed in the future. PMID- 20577291 TI - NHS Evidence - oral health. AB - NHS Evidence - oral health is one of over 30 specialist collections within the NHS Evidence library. Provided by the National Institute for Health and Clinical Excellence (NICE), NHS Evidence was launched in April 2009 with the aim of providing fast and easy access to evidence-based health and social care information. PMID- 20577292 TI - Understanding statistics 1. AB - Understanding the basics of statistics can be quite challenging. One of the problems with statistical analysis is the manner in which it is presented, which is often rather disjointed. This series of articles will attempt to approach statistics by keeping issues in specific categories, to try to facilitate understanding of key concepts. This first article will examine the need for statistical analysis, explore the development of the null hypothesis, and describe what general domains of statistics are used in scientific studies. PMID- 20577293 TI - Valve interventions-a word of caution. PMID- 20577294 TI - Congenital heart conditions: the 'headache' of assessing a link between PFO and migraine. AB - The relationship between patent foramen ovale and migraine is a hotly debated issue. Conflicting data on the association or independence of these conditions have been reported by various study groups around the world. Now, a large-scale case-control study has shown no association between the two entities; however, there were a number of methodological flaws in this study and we are unlikely to see the end of the controversy in the near future. PMID- 20577295 TI - Interventional cardiology: does stent overlap make a difference to clinical outcome? AB - The impact of overlap of drug-eluting stents on clinical and angiographic outcomes is controversial. Individuals with long coronary lesions requiring implantation of multiple stents are an important patient subgroup for whom careful evaluation and decision-making with optimal stent deployment is needed to ensure the best possible short-term and long-term results. PMID- 20577296 TI - Coronary artery disease: revascularization strategies for patients with CAD and diabetes. AB - CABG surgery has been considered the optimal revascularization strategy for patients with diabetes mellitus who have lexft main and/or multivessel coronary artery disease. The results of a new analysis of data from the SYNTAX trial challenge this conventional wisdom and highlight additional coronary revascularization options to physicians and patients. PMID- 20577297 TI - Diabetes: making sense of the rosiglitazone controversy. AB - Whether thiazolidinediones should be used to treat patients with type 2 diabetes mellitus is controversial, as studies on the cardiovascular effects of these drugs have produced conflicting results. A trial in which rosiglitazone and glipizide were compared supports earlier findings that rosiglitazone does not have an adverse effect on the progression of coronary atherosclerosis. PMID- 20577298 TI - Diabetes: glycated hemoglobin is a marker of diabetes and CVD risk. AB - The diagnosis of diabetes mellitus in clinical practice has been mainly based on the measurement of glucose levels in blood. Growing evidence, including results from a new large-scale population study, however, strongly suggests that the assessment of glycated hemoglobin levels has advantages over measurement of glucose levels in predicting the risk of developing diabetes or cardiovascular disease. PMID- 20577300 TI - Nasa patter. PMID- 20577299 TI - Patents. AB - 4,900,116; 4,900,119; 4,906,096; 4,908,832; 4,913,548. PMID- 20577301 TI - Of optics and opticists. PMID- 20577302 TI - Device for reflective dividing of a laser beam with adjustable distance between the two focus spots. AB - For reflective dividing of a laser beam and focusing in two spots with a fixed distance between, a Fresnel biprism is used. When there is a need for a more frequent change of distance between the spots, a new solution is proposed. PMID- 20577303 TI - Stabilization of single frequency internal mirror He-Ne lasers: comment. AB - In the cited article the frequency stability of a singlemode He-Ne laser is concluded from the stability of the laser intensity. We point out that this derivation of frequency stability may show remarkable systematic errors. PMID- 20577304 TI - Optimization of the geometry of a single-pass amplifier. AB - The optimum geometry of a single-pass amplifier containing an active medium through which a light beam propagates is determined to obtain the maximum output power. PMID- 20577305 TI - Technique for enabling prism coupling. AB - An alignment technique has been developed for coupling to optical modes in a waveguide using right angle prisms. PMID- 20577306 TI - Polyimide optical waveguides fabricated with electron beam lithography. AB - Fabrication of PMMA clad polyimide waveguides by electron beam lithography creates very smooth sidewalls allowing production of narrow low loss waveguides on planar substrates. PMID- 20577307 TI - Thermal nonlinear effects in exotic media: application to the study of nonlinear interfaces. AB - Nonlinearities reported as self-focusing in exotic media such as green Chinese tea are identified as thermal selfdefocusing. These large index changes can be used to study hysteresis, power-induced self-switching and cross-switching, the power-induced lensing effect, and other nonlinearities at interfaces. PMID- 20577308 TI - Laser action from 2,6,8-position trisubstituted 1,3,5,7-tetramethylpyrromethene BF(2) complexes: part 1. AB - Of the four new pyrromethene derivatives studied, 1,3,5,7,8-pentamethyl-2,6 diethylpyrromethene-BF(2) complex lased ~3 times more efficiently than rhodamine 560 under flashlamp excitation. PMID- 20577309 TI - Efficient grating coupling to poly-4BCMU optical waveguides. AB - We report measurements of the refractive indices of poly-4BCMU films and the fabrication of an efficient integrated optical distributed coupler. The refractive index measurements were performed in the visible and near IR using blazed-grating couplers. The analysis led to the optimization of an input coupler with a coupling efficiency larger than 45% at 1.064 microm. PMID- 20577310 TI - Scaling rules for nonlinear thin film optical waveguides. AB - A mode power measure is applied to characterize nonlinear thin film optical waveguides in an approach analogous to that of Chelkowski and Chrostowski. Together with the normalized film thickness and the asymmetry coefficient, it allows us to get a concise overview of the waveguiding properties at a given power. For self-focusing film, we discuss the design conditions under which the degree of asymmetry significantly affects the waveguiding properties. PMID- 20577311 TI - Temperature invariance of quantum well modulators using a feedback circuit based on the quantum confined Stark effect. AB - We report the design and performance characteristics of a voltage feedback circuit which can rapidly compensate for the temperature-dependent shift of the excitonic peak energy positions in quantum confined Stark effect modulators. The energy position remains invariant over a temperature shift of 10 degrees . The circuit is simple and can be operated with a single device or an array of modulators. PMID- 20577312 TI - Numerical solution of the exact cavity equations of motion for an unstable optical resonator. AB - We solve numerically, we believe for the first time, the exact cavity equations of motion for a realistic unstable resonator with a simple gain saturation model. The cavity equations of motion, first formulated by Siegman ["Exact Cavity Equations for Lasers with Large Output Coupling," Appl. Phys. Lett. 36, 412-414 (1980)], and which we term the dynamic coupled modes (DCM) method of solution, solve for the full 3-D time dependent electric field inside the optical cavity by expanding the field in terms of the actual diffractive transverse eigenmodes of the bare (gain free) cavity with time varying coefficients. The spatially varying gain serves to couple the bare cavity transverse modes and to scatter power from mode to mode. We show that the DCM method numerically converges with respect to the number of eigenmodes in the basis set. The intracavity intensity in the numerical example shown reaches a steady state, and this steady state distribution is compared with that computed from the traditional Fox and Li approach using a fast Fourier transform propagation algorithm. The output wavefronts from both methods are quite similar, and the computed output powers agree to within 10%. The usefulness and advantages of using this method for predicting the output of a laser, especially pulsed lasers used for coherent detection, are discussed. PMID- 20577313 TI - Material dispersion of graded-index fibers from numerical aperture measurements. AB - The material dispersion of a parabolic graded-index fiber can be completely characterized through numerical aperture measurements. The relation between the dispersion slope and wavelength of zero dispersion is discussed for single-mode fibers, and the corresponding relation for material dispersion in multimode fibers is presented. Then the effective wavelength of zero material dispersion in a multimode fiber is expressed in terms of a quantity that resembles a numerical aperture. Formulas relating that quantity to measured numerical apertures are derived in the Appendix. Starting with just numerical aperture measurements, therefore, one may determine the effective wavelength of zero material dispersion and effective material dispersion slope for a multimode fiber. PMID- 20577314 TI - Enhancement of the nonlinear optical properties of fluorescin doped boric-acid glass through cooling. AB - We examine, both theoretically and experimentally, the temperature dependence of the nonlinear optical response of fluorescein doped boric-acid glass. The third order nonlinear susceptibility is increased by an order of magnitude over its room temperature value to greater than 10 esu by cooling the sample to a temperature below 200 K. PMID- 20577315 TI - Phase and group velocity matching for second harmonic generation of femtosecond pulses. AB - We theoretically analyze a method for matching group velocities of fundamental and second harmonic femtosecond pulses during phase matched frequncy doubling by predispersing the fundamental pulse with a prism. The method permits improved conversion efficiency by allowing crystal lengths of several millimeters without sacrificing second harmonic pulse duration. Second harmonic pulse energy and duration are analyzed for beta-BaB(2)O(4), and limiting experimental factors are discussed. The results show that the method is most advantageous for incident pulses between 0.1- and 1.0-ps duration and microjoule and higher energies and that second harmonic pulse duration and conversion efficiency are not highly sensitive to optical misalignments of the order of 1 degrees . PMID- 20577316 TI - Flat microwave-powered ultraviolet source. AB - A microwave-powered ultraviolet source capable of covering an area as large as a 150-mm Si wafer is developed. Fifteen low pressure mercury discharge lamps are arrayed in a flat microwave cavity. The Hg 254-nm irradiance on the surface 1 cm from the lamps is 120 mW/cm(2) at a microwave power of 1200 W. This UV source is used for photoresist removal. Low pressure cadmium lamps, which have the Cd 229 nm irradiance of 13.9 mW/cm(2) at 1 cm for a 500-W input, are also investigated. PMID- 20577318 TI - Examination of temperature effects on the lasing characteristics of rhodamine cw dye lasers. AB - Experimental investigations on the temperature dependence of fluorescence and lasing characteristics of cw circulating organic dye lasers, excited with the multimode output of an Argon laser, were carried out for Rhodamine B, Rhodamine 6G, and Rhodamine 110 laser solutions in ethylene glycol. Significant improvements in the performance of Rhodamine B were observed as the solvent temperature was reduced below room temperature. These included significant reduction in the threshold pump requirements and a considerable increase in the attainable output power. This is in contrast to the results obtained for Rhodamine 6G and Rhodamine 110. Analysis of the results permit classification of dye lasers into three categories in so far as effects of cooling are concerned. PMID- 20577317 TI - Simple inexpensive method of measuring the temporal spreading of a light pulse propagating in a turbid medium. AB - A simple and inexpensive method of measuring statistical parameters related to the time lengthening arising in the propagation of a light pulse in a turbid medium is presented. The method is based on the repetition of attenuation measurements of a light beam passing through the turbid medium when the absorption coefficient of the medium surrounding the diffusing particles is varied. The measurements are carried out using a cw source and a simple optical receiver with a common photodiode as a detector. The results of two measurements are reported together with the results of numerical simulations carried out using the scattering properties and geometric parameters corresponding to the experimental situation. Numerical results were obtained using a Monte Carlo based method. Good agreement between experimental and numerical results was found. PMID- 20577319 TI - Temperature tuned distributed feedback dye laser with high repetition rate. AB - A pulsed subnanosecond laser system is described which is tunable over the spectral range from 450 to 650 nm with a bandwidth of ~0.006 nm and can be operated with a repetition rate of up to 200 Hz. It consists of a mirror tuned distributed feedback dye laser which is directly pumped by a XeCl excimer laser. Fine tuning and accurate stabilization of the dye laser wavelength are performed by electronically controlling the temperature of the dye liquid. The long-time stability of the laser wavelength is 0.0028 nm; this is achieved by a novel mechanical and electronic arrangement. PMID- 20577320 TI - Scatter matrix algorithm for the transverse Kerr magnetooptic effect in multilayer optical film structures. AB - Multilayer optical structures are considered in which one or more of the layers is magnetotropic. Generalized scattering matrices at the interfaces are derived for the transverse Kerr magnetooptic effect. An algorithm is presented for the calculation of the optical and magnetooptical properties of the structure. PMID- 20577321 TI - Bandwidth and tuning range of an ArF laser measured by 1 + 1 resonantly enhanced multiphoton ionization of NO. AB - The tuning range and bandwidth of an ArF laser were measured using 1 + 1 resonantly enhanced multiphoton ionization of NO. Operated as an injection-seeded oscillator/amplifier combination, the tuning range was 51,560-51,810 cm(-1); operated with single pass amplification of the oscillator, the tuning range was 51,560-51,765 cm(-1). In both cases, the laser bandwidth, determined from the linewidth, was 0.21 +/- 0.06 cm(-1). Rotational lines in the beta(7,0), gamma(3,O), and epsilon(0,1) bands were observed including several previously unreported lines. PMID- 20577322 TI - Absorbing multilayer coatings producing a 90 degrees phase shift. AB - As an example of the great influence the parameters of a multilayer coating have in the absorption, this Technical Note considers five pairs of ThF(4)/ZnS or ThF(4)/CdTe layers on silver at 10.6-microm wavelength at a 45 degrees angle of incidence. PMID- 20577323 TI - Patents. AB - 4,893,003; 4,896,929; 4,907,847; 4,896,928; 4,913,533; 4,913,534; 4,900,134; 4,913,547; 4,914,287; 4,919,501; 4,919,516; 4,919,536; 4,925,261; 4,925,273; 4,925,279; 4,925,281; 4,927,036; 4,927,234; 4,915,463; 4,918,987; 4,920,268; 4,927,254. PMID- 20577324 TI - Of optics and opticists. PMID- 20577326 TI - Topographical measurements of water waves using the projection moire method. AB - The use of projection moire topographical methods to measure water waves is described. The advantages of the optical method are emphasized, and the practical importance of such measurement is discussed. PMID- 20577327 TI - Absorption and scattering of light by small particles: the interference structure. AB - We point out errors in the derivation of the periodicity of the interference structure of the Mie extinction curve, recently published in ABSORPTION AND SCATTERING OFLIGHTBY SMALL PARTICLES, by C. F. Bohren and D. R. Huffman (Wiley, New York, 1983). PMID- 20577328 TI - High dynamic range operation of the Fairchild CCD181 line scan camera. AB - A commerciallya vailables elf-scanningl inears ensora rray has been operated in an unconventional manner to produce an optical dynamic range in excess of 85 dB. PMID- 20577329 TI - Optical differentiation of spectral profiles by a Fabry-Perot etalon. AB - A method is described, which allowsmeasurements with high resolution of spectral profiles superimposed by strong disturbing signals. PMID- 20577331 TI - Second-order imaging properties of circular field spectrographs: erratum. PMID- 20577330 TI - Characterization of some suitable deflecting liquids in photothermal deflection spectroscopy. AB - Generally CCl(4) is used in photothermal deflection spectroscopy as the deflecting medium. We looked for alternative deflecting liquids. This Letter reports the main features of some suitable liquids. PMID- 20577332 TI - Gradient-index optics: introduction by the feature editors. AB - This introduction briefly defines the scope of the feature in this 1 Oct. 1990 issue on gradient-index image systems and discusses where the field is going. The second part of the feature, on microoptics, will appear in an issue later this year. All papers are based on presentations made at the joint symposium MOC/GRIN'89. PMID- 20577333 TI - Current status of aplanatic gradient-index lens systems. AB - A gradient index (GRIN) lens, when processed by a spherical curvature at its endface, yields the equivalent aspheric effect, if the curvature is adequately optimized with refractive index distribution coefficients. Aplanatic lens systems of infinite or finite conjugates can be made by utilizing the new type of GRIN lens. PMID- 20577334 TI - Generalized bending equations for the radial gradient-index optical system. AB - Generalized bending equations and an example of their use for a radial gradient index lens system are described. It is shown that the equations are effective tools in real optical design. PMID- 20577335 TI - Axicon gradient lenses. AB - In a radial gradient, the refractive index profile is normally represented by a polynomial with only even powers of r. If, however, odd powers of r are present in the representation, the effect on aberrations can be serious. A Wood lens serves as an example. PMID- 20577336 TI - Arbitrary single-mode coupling by tapered and nontapered grin fiber lenses. AB - Arbitrary modal field coupling is analyzed and optimized by using tapered and nontapered GRIN fiber lenses as single-mode optical fiber connectors. Conditions for achieving maximum coupling efficiency are derived. PMID- 20577337 TI - Effects of axial and radial gradients on Cooke triplets. AB - This study investigates the role of gradient-index materials in the design of Cooke triplets for use as 35-mm format photographic objectives. Cooke triplet designs are presented with different types of gradient-index profiles. Both linear axial and shallow radial gradients are shown to provide effective control of spherical aberration and astigmatism. In particular, a Cooke triplet with a combination of both linear axial and radial gradients attains performance comparable to a six-element double Gauss lens. In virtually all cases, the use of gradient-index components improves the Cooke triplets' performance significantly. PMID- 20577338 TI - Third-order aberration theory for weak gradient-index lenses. AB - A set of simple analytic expressions has been developed for calculating the third order aberration coefficients in weak or nearly thin axial and radial gradient index lenses. PMID- 20577339 TI - Ray tracing through gradient-index media: recent improvements. AB - A general ray tracing algorithm for gradient-index media that treats various refractive index distributions in a unified manner has been developed by implementing the concept of isoindicial surfaces, position variables, and cubic splines. A novel and simpler algorithm for optical path length calculations is also presented. PMID- 20577340 TI - Design and tolerancing of aspherical and gradient-index germanium singlets of equal performance. AB - Two different aspherical singlets, four types of axial gradient-index singlet, and one radial gradient-index singlet achieving the same performance are toleranced for thickness, curvatures, base index, and special coefficient (aspheric or gradient) sensitivities. The results show that the singlet with the most relaxed tolerances has a linear axial gradient which extends through the lens, followed in order by a singlet with a parabolic radial gradient, a singlet with an aspheric surface on the front, and a singlet with a parabolic axial gradient crossing the first surface. PMID- 20577341 TI - Axial and radial gradient-index titania flint glasses. AB - A series of TiO(2) flint glasses has been developed for producing GRIN glass by ion exchange. Both positive and negative axial and radial gradients were fabricated in high index glasses by exchange of Li(+) for Na(+) and Na(+) for Li(+), respectively. Index changes to 0.05 and depths up to 6 mm were achieved and a wide variety of index profiles are shown. PMID- 20577342 TI - Gradient-index profile control from mixed molten salt baths. AB - The composition of the molten salt bath was shown to exert a strong influence on the gradient-index profile that resulted from the ion exchange of silver for sodium. Two types of additives were used to enhance the ion exchange from a base AgCl melt. Both techniques reduced the profile degradation that normally occurred with long diffusion times, while one technique also increased the refractive index change at 0.6328 microm in a regular fashion from 0.06 to 0.15. PMID- 20577343 TI - Gradient-index silver alumina phosphate glasses by exchange of Na(+) for Ag(+). AB - High index of refraction crown glasses containing silver oxide have been cast from a melt and used for ion exchange experiments. High quality axial and radial gradient-index profiles were fabricated and the interdiffusion coefficient calculated. Index changes up to 0.08 were achieved in a base glass with n(d) = 1.61 and V(d) = 57. PMID- 20577344 TI - Index profile control using Li(+) for Na(+) exchange in aluminosilicate glasses. AB - Two new techniques for altering the gradient-index profile shape are presented using ion exchange of Li(+) for Na(+) in an aluminosilicate glass. By varying the alkali concentration in the base glass and salt melt, the functional form of the index profile is modified to range in shape from convex to concave. The success of these techniques is attributed to the unusual characteristics of the initial system, which are shown to be caused by a nonlinear dependence of refractive index on dopant concentration. PMID- 20577345 TI - Gradient-index doped silica rod lenses produced by a solgel method. AB - Radial-GRIN rod lenses of titanium doped silica have been prepared by a solgel process using metal alkoxides. The obtained rods with parabolic index distribution give high efficiency in coupling with optical fibers as well as good image resolution. Moreover they exhibit good stability in an adverse environment such as high temperature, high humidity, and strong radiation. PMID- 20577346 TI - Multiple imaging and multiple Fourier transformation using planar microlens arrays. AB - A new type of multiple imaging and multiple Fourier transformation system under coherent illumination using microlens arrays has been developed. The optical system is based on geometrical optics instead of convolution or diffraction. As a result, it has the advantage of design flexibility especially in alignment of the duplicate images. The experimental results of the system, which are implemented using planar microlens arrays fabricated by an ion exchange technique, are also discussed. PMID- 20577347 TI - Ion beam assisted deposition of a thin film coating on a gradient-index lens array. AB - A new coating method which employs ion bombardment has been developed for a gradient-index (GRIN) rod lens array using silicone rubber and fiber reinforced plastic plates in its construction. The thin film coatings deposited using this method passed the durability tests on the basis of MIL-M-13508C. The adhesion of the thin film coating was strong and durable enough to allow for use on GRIN rod lens arrays in photocopiers. The effect of ion bombardment has been investigated with thin film analysis data by Fourier transform infrared microspectroscopy and secondary ion mass spectrometry. PMID- 20577348 TI - High numerical aperture planar microlens with swelled structure. AB - The planar microlens is a 2-D integrated microlens fabricated by the selective ion exchange technique. This paper demonstrates a new class of planar microlens which has a high numerical aperture. The new planar microlens uses a swelling structure and index distribution which comes from replacing ions with different ion volumes. Lens diameters from 10 to 400 microm can be fabricated. A numerical aperture larger than 0.5 is achieved when the lens diameter is smaller than 100 microm. Use of this microlens in light coupling between an LD and a single-mode fiber is also evaluated. PMID- 20577349 TI - Pattern edge color difference in a color image sensor with a GRIN rod lens. AB - The color distortion arising around pattern edges of pictures scanned by a color image sensor using a GRIN rod lens is simulated by a model that uses a Gaussian distribution function as the spread function of the lens for two color separation systems. In the time division system, the maximum permissible DeltaH(B) which indicates color aberration is obtained. Although this value depends on some sensor parameters, such as pixel size and pixel period, the method to obtain the maximum permissible DeltaH(B) presented in this paper is suitable in almost all cases. In the space division system, the effect of color aberration on color distortion is clarified, and it is seen that permissible color aberration is larger than that in the time division systems. PMID- 20577350 TI - Multimatched filtering using a microlens array for an optical-neural pattern recognition system. AB - In the optical-neural recognition system proposed for flexible parallel information processing, a planar microlens array is used to form simultaneously many identical Fourier transforms of an input pattern; from each transform the feature extraction of the input pattern is performed in parallel through optical correlations with memorized standard spatial filters. In this paper, it is experimentally shown that the multimatched filtering system, as the optical feature extracting part of the proposed system, can be composed of a planar array of graded index microlenses of 1.05-mm diameter and 2.6-mm focal length. PMID- 20577351 TI - Image multiplexer using a planar microlens array. AB - An image multiplexer (IMX) composed of a planar microlens array is proposed for an input device of an optical parallel processing system. Imaging properties were evaluated experimentally and numerically to find a design rule and the limitations of use of the IMX. As a result, it was found that a planar microlens has a relatively good distortion property and low MTF sensitivity for oblique imaging, even if an image height goes to as high as 60% of the lens radius. Furthermore, a compensation method for image shift nonlinearity is proposed. The effective lens number in an array is estimated. PMID- 20577352 TI - Compound eye systems for nonunity magnification projection. AB - New compound eye systems for nonunity magnification projection are shown. As all the beams of light on the optical axes of erect or inverted real image systems intersect perpendicular to the object and image planes in these systems, it becomes possible to get rid of any local variation in magnification, which deteriorates the image quality of earlier compound eye systems. PMID- 20577353 TI - Adiabatic invariance in GRIN channel waveguides and its use in 3-dB cross couplers. AB - We have extended the local normal mode approach of Burns and Milton to derive the condition for adiabatic invariance in graded-index channel waveguides. The results show that in spite of the index-grading and 2-D confinement, the inequality describing the adiabatic condition is basically the same as that for step-index slab waveguides. To verify the predictions of the theory, we have fabricated, using ion exchange in glass, a cross coupler with two asymmetric input channel waveguides and two symmetric output guides. The experimental results show equal output power (3.0 +/- 0.1 dB) from the two symmetric guides when either of the two unequal guides is excited, demonstrating excellent agreement with the theory. PMID- 20577354 TI - Receiving efficiency of monostatic pulsed coherent lidars. 1: Theory. AB - The receiving efficiency eta as a function of range z is investigated for pulsed coherent lidars using a theory that relates eta(z) to the transmitted laser intensity and the point-source receiving efficiency eta(s)(r,z). The latter can be calculated either by a forward method, or by a backward method that employs the back-propagated local oscillator (BPLO) approach. The BPLO method is efficient and accurate provided that cascaded diffraction effects inside the lidar system are properly taken into account. The theory is applied to the ideal case to examine the optimization of the system when both transmitted and BPLO fields at the antenna are Gaussian, including optimum telescope aperture. PMID- 20577355 TI - Receiving efficiency of monostatic pulsed coherent lidars. 2: Applications. AB - Using the theory developed in Part 1, the receiving efficiency as a function of range, eta(z), is calculated under different conditions for the NOAA/ERL/Wave Propagation Laboratory CO(2) Doppler lidar. Theoretical analyses, numerical calculations, and experimental measurements are carried out to quantify the sensitivity of eta(z) to transmitted laser beam quality, telescope focal setting, telescope power, scanner astigmatism, LO beam divergence, and system misalignment. These results bring insight to the design of practical coherent lidar systems. PMID- 20577356 TI - Doppler lidar atmospheric wind sensor: reevaluation of a 355-nm incoherent Doppler lidar. AB - We reevaluate the performance of an incoherent Doppler lidar system operating at 354.7 nm, based on recent but well-proven Nd:YAG laser technology and currently available optical sensors. For measurements in the lower troposphere, up to ~5 km altitude, and also in the Junge-layer of the lower stratosphere, a wind component accuracy of +/- 2 m/s and a vertical resolution of 1 km should be obtained with a single pulse from a 1-J laser, operating at Polar Platform altitudes (700-850 km) and high scan angles (55 degrees ). For wind measurements in the upper troposphere (above ~5 km altitude) and stratosphere (above and below the Junge layer) the concentration of scatterers is much lower and higher energies would be required to maintain +/-2m/s accuracy and 1 km vertical resolution, using single laser pulses. Except for the region in the vicinity of the tropopause (10 km altitude), a 5-J pulse would be appropriate to make measurements in these regions. The worst case is encountered near 10 km altitude, where we calculate that a 15-J pulse would be required. To reduce this energy requirement, we would propose to degrade the altitude resolution from 1 km to 2-3 km, and also to consider averaging multiple pulses. Degrading the vertical and horizontal resolution could provide an acceptable method of obtaining the required wind accuracy without the penalty of using a laser of higher output power. We believe that a Doppler lidar system, employing a near ultraviolet laser with a pulse energy of 5 J, could achieve the performance objectives required by the major potential users of a global space-borne wind observing system. PMID- 20577357 TI - Optimizing a pulsed Doppler lidar. AB - NOAA's fieldable injection-seeded, pulsed, coherent CO(2) lidar was developed over a 5-yr period. Its performance and reliability are characterized. Techniques for calibration, alignment, collimation, and for improving detector performance and frequency stability are presented. PMID- 20577358 TI - Miniature laser light scattering instrumentation for particle size analysis. AB - We describe the design, construction, and testing of a miniature, all-solid state laser light scattering instrument for determination of particle sizes and distributions using photon correlation spectroscopy techniques (i.e., quasielastic or dynamic light scattering). Detailed comparative tests with standard photon correlation spectroscopy equipment are presented. PMID- 20577359 TI - Multiple scattering corrections for lidar detection of obscured objects. AB - The importance of multiple scattering for lidar detection of a spherical object obscured by an aerosol is assessed using Monte Carlo radiative transfer calculations. Multiple scattering correction factors are significant and depend on the location and size of the object, and the field of view and time resolution of the detector. PMID- 20577360 TI - Small angle bidirectional reflectance distribution function. AB - Small angle scattering in and near the specular direction has recently been measured with a monostatic laser interferometric reflectometer for a laser beam incident normal to the surface. Employing the Ricean statistics of the amplitude distribution for coherent glint with an additive scattered component of speckles, the scattered portion has been partitioned from the total reflected signal at 1.06 and 10.6 mum. Such measurements are basic to surface metrology and useful in assessing the performance of mirrors used in lasers and astronomical telescopes. PMID- 20577361 TI - Mie scattering used to determine spherical bubble oscillations. AB - Linearly polarized laser light is scattered from an oscillating, acoustically levitated bubble, and the scattered intensity is measured with a suitable photodetector. The output photodetector current is converted into a voltage and digitized. For spherical bubbles, the scattered intensity I(rel)(R,theta,t) as a function of radius R and angle theta is calculated theoretically by solving the boundary value problem (Mie theory) for the water-bubble interface. The inverse transfer function R(I) is obtained by integrating over the photodetector solid angle centered at some constant theta. Using R(I) as a look-up table, the radius vs time [R(t)] response is calculated from the measured intensity vs time [I(exp)(R,t)]. PMID- 20577362 TI - Reflection functions for inhomogeneous land surfaces. AB - Bidirectional reflection distribution functions (BRDFs) of inhomogeneous land surfaces that consist of protruding structures on a flat suface are modeled. The components are allowed to have individual reflection properties. Modeling the BRDFs takes into account the simultaneous influence of vertical structure and of different anisotropic BRDFs assigned to the components. A realistic simulation of bare soil and partly or fully vegetated surfaces with a pronounced 3-D structure is possible. A sensitivity study shows to what extent surface reflection is affected by vertical structure and zenith angle of incidence when different BRDFs are assigned to both surface components. The results can be used to decide for which conditions area weighted adding of BRDFs from homogeneous surfaces is sufficient to get an average BRDF for an inhomogeneous surface. It tends to be insufficient when vertical structure, zenith angle of incidence, and the albedo of the ground increase in relation to the albedo of the protrusions. PMID- 20577363 TI - Influence of high altitude clouds on upper tropospheric radiance measurements. AB - Altitude profiles of atmospheric window radiance measured with upward-looking sensors frequently show a rapid decrease in radiance with increasing height over a narrow altitude region in the upper troposphere. This region of rapid decrease is termed a radiometric knee in the altitude profile. The top of this knee defines a radiometric tropopause with a latitudinal height dependence similar to that of the usually defined barometric tropopause. Atmospheric window (10-12 microm) radiance at these altitudes can be associated with the presence of ice particulates. Comparison of the measurements with predicted altitude profiles of atmospheric radiance from the LOWTRAN 7 atmospheric model code shows that a well defined knee occurs when there is a cloud layer (liquid or ice) such as a subvisual cirrus cloud present. The rate and magnitude of the radiance decrease depend on the optical depth and, therefore, the water content of the layer. Atmospheric background radiance values for near horizontal (large zenith angle) viewing with upward-looking sensors can be as much as a factor of 100 lower above the knee than below it. Comparisons between calculated and observed radiance profiles were used to estimate the vertical extent, total optical depth, and water content of the clouds. PMID- 20577364 TI - Astigmatism together with longitudinal focal shift in off-axis optical systems. AB - In many laser applications optical systems are employed to focus off-axis beams that only partially fill the system aperture. In this paper analytical expressions that give the position of the diffraction focus, normalized peak intensity, and tolerance conditions for uniform and Gaussian off-axis beams in an optical system which suffers from astigmatism together with longitudinal focal shift aberration are obtained on the basis of diffraction theory. The results are useful for designing focusing systems for use with laser beams. PMID- 20577365 TI - Temperature dependent nonlinearity effects of a QED-200 detector in the visible. AB - The spectral response of the United Detector Technologies model QED-200 quantum efficiency detector, along with that of other photodiodes, has been measured for two different wavelengths in the visible. The QED shows a strong temperature dependent response at certain power levels. It is shown that the effect comes from an increase in internal quantum efficiency due to a supralinearity effect at power levels of ~1 mW. PMID- 20577366 TI - Michelson interferometer with a rotating retroreflector: a laboratory model for environmental monitoring. AB - Designed for atmospheric pollution monitoring, a breadboard model of a new Michelson interferometer has been developed. It utilizes a nutating retroreflector to generate alterations in the geometrical and optical paths. The forward-backward stop-and-go movement of a reflecting element of conventional Michelson interferometers is thus replaced by a continuous rotation. At this state the instrument employs a 6.3-cm (2.5-in.) diam rotating retroreflector, a ZnSe beam splitter, and a HgCdTe detector at liquid nitrogen temperature, sensitive in the 8-14-microm band. It allows spectral resolutions of up to 2 cm( 1). The device is linked via an analog digital interface to a desktop computer which performs interferometer control, data acquisition, Fourier transform, and display of the spectra. PMID- 20577367 TI - Double exposure hologram of hyperbolic fringes and its use in the measurement of optical coherence. AB - A hologram of hyperbolic fringes generated by double exposure is presented in this paper. The principle and experimental results of using it to measure optical coherence are given as well. PMID- 20577368 TI - Collinear photothermal deflection spectroscopy with light-scattering samples. AB - An analytical model that incorporates effects of light scattering was developed for dual-beam photothermal deflection spectroscopy. Thermal gradients induced by a modulated excitation beam deflect an optical probe beam which was treated as being of finite dimensions. Mechanisms by which thermal gradients produce refractive index gradients are discussed, with an explicit expression for dn/dT being derived. Experimental studies with suspensions of small latex particles in Nd(3+) solutions demonstrated that the model accurately predicts both the shape of the deflection signal and the attenuation of the signal due to light scattering. The absolute magnitude of the observed signal is approximately predicted by theory. PMID- 20577369 TI - Polarized light, the integrating sphere, and target calibration. AB - In this paper the calibration of nonideal diffuse targets is discussed where the targets are irradiated by polarized light. Both measurements of conical hemispherical or directional-hemispherical and bihemispherical reflectance are discussed. The targets do not depolarize the incident light and in some cases the wall of the integrating sphere may not be depolarizing and must be represented by a Mueller reflectance matrix. This means that the usual comparison technique of targets based on the scalar theory does not apply. PMID- 20577370 TI - Photothermal radiometry measurement of thermal diffusivity. AB - A method of measuring the thermal diffusivity of solid material at room temperature with photothermal radiometry is described. By measuring the amplitude and phase frequency characteristics of the photothermal signal, the thermal diffusivity is calculated and compared with the value obtained by the pulsed laser conductometer method. PMID- 20577371 TI - Laser scanning microscope with a differential heterodyne optical probe. AB - A new laser scanning microscope system has been developed to observe the spatial distribution of light scattering particles or defects in a partially transparent object. The present microscope has an optical probe whose intensity is modulated by the interference effect between two crossed laser beams with slightly different frequencies. In this paper, a Zeeman laser combined with a simple polarizing optical system is used to produce two such coherent beams. Experimental results obtained by using a latex sphere and a microscale as the target show qualitatively that high image contrast is obtained by the present method even if some obscuring particles exist in front of the probe volume. Distributions of light scattering particles or defects in a LiNbO(3) and TGS single crystal can be visualized by a computer-controlled scan stage. PMID- 20577372 TI - Grazing incidence Czerny-Turner monochromator utilizing sagittal focusing mirrors. AB - A new soft x-ray monochromator design, especially conceived for high brightness undulator radiation, is discussed. Its aim is to achieve a resolution limited only by grating figuring slope errors, together with a simple grating rotation scanning; thereby operating with fixed entrance and exit slits. Three cylindrical optical surfaces are employed between the slits, including two mirrors focusing in their sagittal planes, and a resolution lambda/Deltalambda up to approximately 14000 at the carbon K-edge is predicted. Its implementation for the planned Trieste synchrotron radiation facility is described in detail. PMID- 20577373 TI - Ray tracing analysis of the image quality of a high collection efficiency mirror system. AB - Recently, a high collection efficiency mirror system was developed by Watson [Cytometry 10, 681-688 (1989)] to increase the sensitivity of low level fluorescence detection. The mirror system consists of an ellipsoidal imaging mirror and spherical backreflecting mirror. The fluorescing sample is located at one focus of the ellipsoid, and its image is formed at the other focus. In this paper we evaluate the image quality of this geometry using a PC-based ray tracing program. The analysis demonstrates high collection efficiency but poor image quality. The effect of poor image quality on single molecule detection is discussed. PMID- 20577374 TI - Single photomask, multilevel kinoforms in quartz and photoresist: manufacture and evaluation. AB - Kinoforms manufactured in photoresist by photolithographic techniques using a single, ten-level, grey scale photomask, exposed in a specially designed laser exposure system, are described. Kinoforms designed for uniform as well as for partial Gaussian beam illumination are discussed. The highest measured diffraction efficiency was 55%. Photoresist kinoforms were transferred into quartz substrates by reactive ion etching. The highest measured diffraction efficiency for the resulting all-quartz kinoforms was 53%. PMID- 20577375 TI - Application of the impedance formalism to diffraction gratings with multiple coating layers. AB - The standard method of matching boundary conditions at the interfaces of a multilayer plane dielectric stack is shown to be numerically unstable for the evanescent orders when a large number of layers is present. For an isolated dielectric stack with an incident propagating beam there is no need to calculate the evanescent orders; however, when a diffraction grating is buried under the stack there is mixing of orders, and it may be important to calculate the evanescent as well as the propagating orders. It is shown that the impedance formalism removes the numerical instability completely. This method may be coupled to either boundary integral or differential equation methods for the grating to provide the complete solution for the grating-stack system. PMID- 20577376 TI - Triangular coordinate graphical presentation of the optical performance of a semitransparent metal film. AB - The optical performance of an ideal thin film can be represented by a single point on a triangular coordinate graph, because the sum of the reflectance, transmittance, and absorption is unity. Several examples are presented to show how the triangular coordinate graph provides a useful perspective to the interplay between the performance and the optical properties of a semitransparent metal film. PMID- 20577377 TI - Measurements of absorption losses in TiO(2) films by a collinear photothermal deflection technique. AB - We review the principle of photothermal deflection for measuring absorption losses in TiO(2)films. A collinear arrangement gives the best sensitivity for the detection of losses in a low absorbing film deposited on a transparent substrate. The nineteen TiO(2) films produced by six different processes (electron beam evaporation, ion assisted deposition, ion beam sputtering, ion plating, ...), discussed at the 1986 Optical Society of America annual meeting, are measured by this technique. The extinction coefficients of the different films do not show obvious correlation with the deposition method. An important fact is that we have detected a variation in absorption as a function of time on some layers. This absorption shift is connected with the illumination conditions of the sample under study (wavelength: 600 nm; incident power: 400 W/cm(2)). Experimental results over time are given. The evolution of the photothermal signal is different from one sample to another. This phenomenon is partially reversible and depends on moisture degree of atmosphere. PMID- 20577378 TI - Vacuum ultraviolet thin films. 1: Optical constants of BaF(2), CaF(2), LaF(3), MgF(2), Al(2)O(3), HfO(2), and SiO(2) thin films. AB - The optical constants of MgF(2) (bulk) and BaF(2), CaF(2), LaF(3), MgF(2), Al(2)O(3), HfO(2), and SiO(2) films deposited on MgF(2) substrates are determined from photometric measurements through an iteration process of matching calculated and measured values of the reflectance and transmittance in the 120-230-nm vacuum ultraviolet wavelength region. The potential use of the listed fluorides and oxides as vacuum ultraviolet coating materials is discussed in part 2 of this paper. PMID- 20577379 TI - Vacuum ultraviolet thin films. 2: Vacuum ultraviolet all-dielectric narrowband filters. AB - We report the design and performance of narrowband transmission filters employing the rapidly changing extinction coefficient that is characteristic of BaF(2) and SiO(2) films within certain wavelength intervals in the vacuum ultraviolet. We demonstrate the design concept for two filters centered at 135 nm for BaF(2) and at 141 nm for SiO(2). It is found that these filters provide excellent narrowband spectral performance when combined with narrowband reflection filters. The filter centered at 135 nm has a peak transmittance of 24% and a bandwidth of 4 nm at full width at half-maximum for collimated incident light. The transmittance for lambda(0) 60% at lambda = 68 A, and>40% at lambda approximately 920 A, for RbBr photocathode layers applied to the surface of microchannel plates (MCPs). The photoelectric threshold is observed at lambda approximately 1560 A, and there is a broad ( approximately 100-A) QDE minimum centered at lambda approximately 775 A which correlates with 2x the band gap energy for RbBr. The QDE is characterized by four peaks centered at lambda approximately 68 A, lambda approximately 400 A, lambda approximately 600 A, and approximately 1050 A. The QDE peaks at lambda approximately 400 A, approximately 600 A, and approximately 1050 A correspond with emission of 3, 2, and 1 photoelectrons, respectively. The QDE at the lambda approximately 68-A peak is associated with a d-f resonant absorption feature of RbBr. QDE contributions of the photocathode material inside the channels, and on the interchannel web, have been determined. Measurements of the angular variation of the QDE from 0 degrees to 35 degrees to the channel axis are also presented. We describe a simple QDE model and show that its predictions are in accord with the QDE measurements. Preliminary assessment of the stability of RbBr indicates that no QDE degradation occurs after limited exposure (20 h) to air at low humidity (<30%). Examination of the photocathode structure with an electron microscope reveals a rough surface with a scale of the order of 0.5 microm. PMID- 20577452 TI - Comparison of two cryogenic radiometers by determining the absolute spectral responsivity of silicon photodiodes with an uncertainty of 0.02%. AB - To substantiate the NPL primary standard cryogenic radiometer as an absolute instrument it has been compared with the cryogenic radiometer which was successfully used to determine the Stefan-Boltzmann constant. The comparison was carried out with an accuracy of better than 0.02% by the independent determination of the spectral responsivity of silicon photodiodes with each radiometer. Only a detector comprising a number of silicon photodiodes (a trap device) had the required stability to achieve the desired accuracy. Four trap devices were found to have near unity internal quantum efficiency, being self consistent to within 0.01%. PMID- 20577453 TI - Surface plasmon immunoassay. AB - The most sensitive existing assays used to determine antibody levels in blood serum samples require a tracer material, e.g., radioisotope, fluorofore, or enzyme, to identify the specific analyte. Surface plasmon spectroscopy has been applied recently as a no-label technique for the assay of specific antibody solutions with the antigen proteins immobilized on a metal surface. It is found that the metal surface configuration originally proposed for the surface plasmon immunoassay (SPI) is unstable and unsuitable for the assay of specific antibodies in a large mixture of proteins such as in a blood serum. Nevertheless, by properly designing the metal surface structure, the SPI can be made an extremely practical device. Preliminary results for the assay of dinitrophenyl (DNP) and keyhole limpet hemocyanin (KLH) antibodies in blood serum samples, indicate that the SPI, in addition to providing a simple and fast measurement, is comparable with existing approaches, such as radioimmunoassy or enzyme-linked immunosorbent assay both in sensitivity and specificity. PMID- 20577454 TI - Use of objective lenses with slit pupil functions in the imaging of line structures. AB - We consider the imaging of line structures in confocal imaging systems and show that some advantages result if we employ a slit pupil function in one of the lenses. As an example it is found that the gradient of the image of a straightedge is 17.8% sharper than in a traditional confocal microscope. Another attraction is that theoretical imaging calculations are often possible in terms of simple analytic functions. Experimental results and images are presented which are compared with traditional confocal systems as well as those employing incoherent slit detectors. PMID- 20577455 TI - Differential phase quadrature surface profiling interferometer. AB - This paper describes an optical surface profiling system based on phase quadrature differential interferometry. The optical path difference between two adjacent optical probe beams is measured. Interference phase calculation and sample scanning is controlled by a PC computer. Height sensitivity is of the order of 1 nm and lateral resolution is ~10 microm. Results are given which demonstrate the reproducibility and stability of the system. PMID- 20577456 TI - Refractive index detector using Zeeman interferometry. AB - We discuss the theory and error analysis for an ultrasensitive refractive index detector based on the two frequency Zeeman effect laser. Experimental measurements on gases agree fairly well with predictions. With a 5-cm pathlength, the typical interferometry stability is Deltan = 8 x 10(-9)/h. Resolution is Deltan = 1 x 10(-9). PMID- 20577457 TI - Influence of the lamp windows in end-on measurements of the refractivity in a pulsed plasma. AB - During measurement of the refractivity of a pulsed plasma, we have detected, with the help of a Jaminlike interferometer, the optical path variation caused by lamp windows. We attribute this variation to two causes: mechanical vibration and the slow cooling that follows the sharp heating. We conclude that neither has any influence on the measurement of plasma refractivity. PMID- 20577459 TI - Nasa patter. PMID- 20577458 TI - Improved sensitivity in sensor fibers by the proper source/coating selection. AB - The dependence of the optical attenuation on the fiber coating has been measured for a sensor fiber subjected to periodic microbending. The dependence on the spectral characteristics of the selected light sources is also addressed and the proper source/coating combination is discussed. Results indicate that the proper selection of this combination is of crucial importance in the design, development, and performance of fiber optic sensors in which intensity modulated microbending transducers are considered. A combination of a short wavelength for the light source and a fiber coated with a hard, elastomeric material seems to be the optimal selection for enhancing the sensitivity in controlled microbending experiments with applications to fiber optic sensors. The highest sensitivity to microbending was obtained for a nylon coated fiber and using a He-Ne laser at 632.8 nm. PMID- 20577460 TI - Holographic sundial. AB - We discuss a method of constructing white light holograms that can serve as sundials and in other applications. Arrangements with both digital and analog readouts are examined. PMID- 20577461 TI - Holographic interferometric microscope on the basis of a Bi(12)TiO(20) crystal. AB - The applicability of cubic photorefractive crystals in which the recording can be fixed to holographic interferometric studies of microobjects is outlined. The possibility of observing the temporal behavior of the object by a method combining double exposure and real time interferometry is experimentally demonstrated. PMID- 20577462 TI - Methylene blue sensitized dichromated gelatin holograms: influence of the moisture on their exposure and diffraction efficiency. AB - Dependence of the moisture of the plate on the hologram characteristics is studied for methylene blue sensitized dichromated gelatin. The maximum diffraction efficiency increases, and the exposure to obtain a certain amount of diffraction efficiency is reduced for the red light when the moisture of the gelatin layer is properly controlled during exposure. The photochemical reaction of the plate is briefly discussed, and the result of the double exposed hologram is also presented. PMID- 20577463 TI - Reconstruction in inclined planes of curved computer generated holograms. AB - The determination of the complex amplitude in the hologram is one major step in the realization of computer generated holograms. Usually the input distribution is assumed to be in a plane parallel to the hologram plane. However, sometimes a more flexible geometry is of interest. Here, in particular an arbitrarily shaped computer generated hologram of a plane input distribution is considered. The calculation of the complex amplitude in the hologram mainly consists of a Fourier transformation and a nonlinear coordinate transformation. The feasibility of this procedure is demonstrated by optical reconstructions of cylindrically shaped computer generated holograms in arbitrarily oriented planes. PMID- 20577464 TI - Acoustooptic analysis of high frequency wideband sound field schlieren imaging. AB - Schlieren imaging of acoustic waves has been used routinely for at least half a century. The nature of the image has conventionally been analyzed by various ray tracing techniques or wavefront corrugation calculations. These are restricted to low sound frequencies or thin sound fields. We present a novel method, based on acoustooptic plane wave interaction theory, that not only is applicable to high frequencies but reveals some unexpected features of schlieren imaging. PMID- 20577465 TI - Phase selection of synthetic discriminant function filters. AB - In this paper, we address the problem of correlation peak phase selection for synthetic discriminant function filters. We show that the minimization of the output variance and the optimization of the correlation peak form are problems of the same complexity (analogous to the determination of the ground state of a magnetic disordered system). We propose a general framework and, with examples, we show that, although the variance reduction by a proper selection of the correlation peak phases can be interesting in some situations, the optimization of the sharpness of the correlation peak is often more fruitful. PMID- 20577466 TI - Amplitude compensated matched filters using circular harmonic expansion and a Mellin transform. AB - The new techniques of amplitude compensated matched filtering using circular harmonic expansion and a Mellin transform are presented. These techniques yield much better discrimination and sharper autocorrelation peaks compared with the classical matched spatial filtering. Aside from these advantages, the amplitude compensated circular harmonic expansion matched filtering can also yield rotation invariance, and the amplitude compensated Mellin transform matched filtering can yield scale invariance. By computer simulation, we have verified the unique advantages of the new methods. We also provide 3-D graphs of autocorrelation and cross correlation. PMID- 20577467 TI - Shift and projection invariant pattern recognition using logarithmic harmonics. AB - Optical correlation schemes based on a matched filter containing a single logarithmic harmonic of an object are described. This correlator can provide shift and projection (tilt) invariant pattern recognition. The logarithmic harmonics, their orthogonality, and their completeness are presented, as well as experimental results using computer simulations and real optical targets. The projection invariance and the discrimination ability of this filter are successfully demonstrated. PMID- 20577468 TI - Parallel distributed processing model with local space-invariant interconnections and its optical architecture. AB - This paper proposes a parallel distributed processing model with local space invariant interconnections, which is more readily implemented by optics and is able to classify patterns correctly, even if they have been shifted or distorted. Error backpropagation is used as a training algorithm. Computer simulation results presented indicate that the processing is effective and the network can deal with the shifted or distorted patterns. Moreover, the optical implementation architecture using matched filters for the model is discussed. PMID- 20577469 TI - Feedback network with space invariant coupling. AB - Processing images by a neural network means performing a repeated sequence of operations on the images. The sequence consists of a general linear transformation and a nonlinear mapping of pixel intensities. The general (shift variant) linear transformation is time consuming for large images if done with a serial computer. A shift invariant linear transformation can be implemented much easier by fast Fourier transform or optically, but the shift invariant transform has fewer degrees of freedom because the coupling matrix is Toeplitz. We present a neural convolution network with shift invariant coupling that nevertheless exhibits autoassociative restoration of distorted images. Besides the simple implementation, the network has one more advantage: associative recall does not depend on object position. PMID- 20577470 TI - Use of electron trapping materials in optical signal processing. 1: Parallel Boolean logic. AB - Novel electron trapping materials capable of performing optical parallel Boolean logic operations are described. An application to binary full addition based on a parallel algorithm is discussed, and experimental results are presented. PMID- 20577472 TI - Toward a fundamental image preprocessor. AB - A general transformation equation is derived and applied to dynamic and static image differences. It uses translation, rotation, scale, and velocity changes as fundamental object features for image segmentation. A linear minimization algorithm is derived based on a spatial smoothness constraint. The transformation and algorithm constitute an automatic target recognition preprocessor architecture. PMID- 20577471 TI - Image enhancement by nonlinear signal processing. AB - We present a nonlinear joint transform processor that can perform image enhancement. Image enhancement results are obtained for different degrees of nonlinearity applied to the joint power spectrum. The first-order harmonic term at the output plane produces the enhanced image which has the exact Fourier phase of the input image and a Fourier magnitude of the input modified by the nonlinearity. For compression types of nonlinearity, the thresholding will redistribute the energy in the Fourier magnitude of the image by increasing the magnitude of the higher spatial frequencies. Thus, the fine details of the image that are contained in the high spatial frequencies of the joint power spectrum are enhanced. We investigate the effects of various types of nonlinearity on the enhanced images. Analytical expressions for the enhanced images obtained by the nonlinear technique will be provided. Computer simulations of the nonlinear processor for image enhancement are presented to study the performance of the system. We show that the nonlinear technique produces reasonably good results and that it provides much better light efficiency when compared with the block spatial filtering technique. PMID- 20577473 TI - Limits of chirped pulse compression with an unchirped Bragg grating filter. AB - It has been suggested that the large value of group velocity dispersion (GVD) found in a Bragg grating filter written in an optical waveguide could be used for pulse compression. Three expressions are derived relating the compression ratio to the value of GVD and to the bandwidth over which GVD is nearly constant. It is shown that the maximum compression ratio that can be achieved with an unchirped grating is severely limited by the small bandwidth of the high dispersion regions in the transmission spectrum of the filter. PMID- 20577474 TI - Patents. AB - 4,880,290; 4,881,791; 4,896,942; 4,900,114; 4,909,583. PMID- 20577476 TI - Investigation of simultaneous two-photon H and single photon OH excitation in flames using a single dye laser. PMID- 20577475 TI - Of optics and opticists. PMID- 20577477 TI - Laser applications to chemical analysis: introduction by the feature editors. AB - This introduction briefly describes the motivation behind this feature issue on laser applications to chemical analysis. PMID- 20577478 TI - Simultaneous multiple species detection in a flame using laser-induced fluorescence: Errata. AB - An approach for simultaneous detection of NO, OH and O in flames using laser induced fluorescence is presented. The technique is based on spectral coincidences using a Nd:YAG-based laser system producing a frequency-doubled and frequency-mixed laser beam at 287 and 226 nm, respectively. The possibility of making spatially resolved measurements using a diode-array detector was also investigated. The use of this technique for studying potential laser-induced disturbances was also demonstrated. PMID- 20577479 TI - Photochemical effects in multiple species fluorescence imaging in hydrogen nitrous oxide flames. AB - We describe photochemical perturbations observed in flame studies using multiple species fluorescence imaging techniques. We model these perturbations using a sequential two-step mechanism that is specific to flames containing significant quantities of nitrous oxide: [equation], followed by O((1)D) + H(2)O ? 2OH. PMID- 20577480 TI - Laser in situ monitoring of combustion processes. AB - Several examples of laser in situ monitoring of combustion processes are presented. Using a frequency modulated (13)CO(2) waveguide laser, in situ concentrations of NH(3) down to 1 ppm were measured at temperatures up to 600 degrees C in waste incinerators and power or chemical plants. Following ignition of CH(3)OH-O(2) mixtures by a TEA CO(2) laser, gas temperature profiles were measured using rapid scanning tunable diode laser spectroscopy of CO molecules. In laminar CH(4)-air counterflow diffusion flames at atmospheric pressure absolute concentrations, temperatures, and collisional lifetimes of OH radicals were determined by 2-D and picosecond LIF and absorption spectroscopy. Two dimensional LIF and Mie scattering were used to observe fuel injection and combustion in a diesel engine. PMID- 20577481 TI - Method for measuring temperatures and densities in hypersonic wind tunnel air flows using laser-induced O(2) fluorescence. AB - Laser-induced fluorescence in oxygen, in combination with Raman scattering, is shown to be an accurate means by which temperature, density, and their fluctuations owing to turbulence can be measured in air flows associated with high speed wind tunnels. For temperatures above 60 K and densities above 0.01 amagat, the uncertainties in the temperature and density measurements can be <2%, if the signal uncertainties are dominated by photon statistical noise. The measurements are unaffected by collisional quenching and can be achieved with laser fluences for which nonlinear effects are insignificant. Temperature measurements using laser-induced fluorescence alone have been demonstrated at known densities in the range of low temperatures and densities which are expected in a hypersonic wind tunnel. PMID- 20577482 TI - Selection of spectral lines for combustion diagnostics. AB - This paper reports part of our effort to develop practical systematic techniques for measurements in high temperature gases using laser absorption spectroscopy. We present a brief summary of the analysis techniques we have developed for line of-sight measurements. We show that the accuracy of the absorption measurement in a given experiment is largely determined by the spectral lines used for the measurement. Thus the selection of spectral lines is critical for the success of a diagnostic measurement. In this paper, we propose a set of criteria for selecting spectral transitions for temperature and concentration measurements at various experimental conditions. They include the requirements for spectral line resolution, absorption strength, sensitivity, and insensitivity to systematic errors. These rules could be implemented in an expert system. A simplified version of the selection criteria was implemented in a PASCAL program. The capabilities of the program are demonstrated by the selection of absorption transitions of CO for simultaneous temperature and species concentration measurements at several experimental conditions. The criteria and program may be readily extended to other spectroscopic techniques such as laser-induced fluorescence. PMID- 20577483 TI - Signal detection efficiency in multiphoton ionization flame measurements. AB - Multiphoton ionization is often the most sensitive method available for detecting radical species in flame environments. To make accurate relative concentration measurements, however, the electron (or ion) detection efficiency as a function of flame position must be known. Two methods are presented for determining this quantity in a laminar CH(4)/air diffusion flame burning at atmospheric pressure: (1) simultaneous detection of ionization and fluorescence in CO, following two photon excitation of the B(1)Sigma(+) state at 230.0 nm; (2) comparison of 3 + 1 multiphoton ionization of the 4' state of argon at 314.4 nm with mass spectrometric measurements. The results show significant variation of the electron detection efficiency in the lean, stoichiometric, and rich flame regions, with the greatest detection sensitivity observed in the high temperature, primary reaction zones (i.e., near stoichiometric conditions). Corrections to multiphoton ionization data obtained for H atoms are discussed in terms of determining relative concentration profiles across the methane/air diffusion flame. PMID- 20577484 TI - Tunable laser flash absorption: a new technique for measuring rates and yields of chemical reactions at high temperatures. AB - The flash absorption technique, whereby light from an excimer laser is used to measure the kinetic behavior of absorbing species in the high temperature region behind a shock front with a linear array detector, has been extended by using tunable light from a high resolution, pulsed dye laser. The use of narrowband, tunable light allows us to access isolated rovibronic transitions and, thereby, obtain state-specific kinetic information. If the oscillator strength of the transition and the absorption line profile are known, the absolute concentration may be determined. We demonstrate the technique by measuring the temporal development of the hydroxyl radical as it is formed after propane has been thermally dissociated in the presence of oxygen. We conclude that accurate kinetic measurements can be made with hydroxyl concentrations of 10(15) cm(-3) This technique may also be applied to study any species which absorbs below 50,000 cm(-1). PMID- 20577485 TI - Infrared detection of liquids on terrestrial surfaces by CO(2) laser heating. AB - The strong mid-infrared bands of contaminant liquids wetting sand and soil can be remotely detected by 0.103-eV laser irradiation with beam intensity well below that which chars the terrain. Emissions from heated nonvolatile interstitial liquid layers and extinction of thermoluminescence by beam-generated vapors of volatile contaminants are spectrally distinct within the infrared contaminant fingerprint spectral region-as measured by a Michelson interferometer based FT-IR radiometer instrument. The contaminant's vibrational resonance intensities change proportionally in magnitude and sign in measured contiguous difference FFT spectra, within a specific beam-to-sample dwell period. The onset irradiation time and period for detecting these bands can differ according to amount and volatility of contaminant, beam intensity and its time of dwell necessary to produce sufficient thermoluminescence flux, and on the quantity of interferogram data acquisitions. PMID- 20577486 TI - Lidar measurements of stratospheric ozone and intercomparisons and validation. AB - A ground-based, high power differential absorption lidar (DIAL) system has been implemented to make long term, precise measurements of stratospheric ozone concentration profiles from ~20- to 50-km altitude. This lidar is located at an elevation of 2300 m in the San Gabriel Mountains, Southern California, and has been in operation since January 1988. Evaluation of the results obtained from this system has been provided through an inter-comparison campaign, carried out during October/November 1988, and through long term comparison with SAGE II satellite measurements. This paper describes the implementation of the system and its operation, including the procedures for data analysis. Examples of ozone profiles measured and inter-comparisons with measurements made by other instruments are presented which show that the lidar is capable of producing high quality ozone measurements up to at least 45-km altitude. PMID- 20577487 TI - Atmospheric ammonia measurement using a VUV/photo-fragmentation laser-induced fluorescence technique. AB - Vacuum ultraviolet/photofragmentation laser-induced fluorescence has been demonstrated to be a highly specific and sensitive method for the quantitative measurement of atmospheric ammonia (NH(3)). The fluorescence detected in this approach results from the two 193-nm photon photofragmentation step NH(3)?NH(2)? NH(b(1)Sigma(+)) followed by the excitation of the NH(b(1)Sigma(+)) NH(c(1)Pi) transition via a 450-nm photon with final emission being observed from the NH(c(1) Pi) NH(a(1)Delta) transition at 325 nm. Limits of detection for the instrumentpresented here are < 10 pptv and < 4 pptv for 1- and 5-min integration periods, respectively, in ambient sampling conditions. The technique is free from interferences and system performance does not significantly degrade in adverse sampling conditions (i.e., rain, fog, clouds, haze, etc.). Spectroscopic selectivity in the NH(b(1)Sigma(+))?NH(c(1)Pi) transition is sufficient to resolve (15)NH(3) and (14)NH(3) contributions for use in atmospheric tracer studies. Average ammonia measurements at Stone Mountain, GA, ranged from approximately 110 pptv for air temperatures <5 degrees C to approximately 240 pptv for air temperatures >/=<5 degrees C over the period from Dec. 1987 to the end of Apr. 1988. PMID- 20577488 TI - Resonance ionization mass spectrometry of AI(x)Ga(1-x)As: depth resolution, sensitivity, and matrix effects. AB - Resonance ionization mass spectrometry (RIMS) of neutral atoms sputtered from III V compound semiconductors such as Al(x)Ga(1-x)As provides information that is complementary to secondary ion mass spectrometry with the added advantages of rejecting mass interferences, retaining good sensitivity, and reducing matrix effects. A GaAs sample, delta doped with Be, is used to measure depth resolution and Be secondary ion and atom yield. Because of the coupling of the pulsed RIMS lasers and continuous sputtering beam, duty cycle factors are used to determine the atom yield. A 3-D model of the geometrical overlap of laser and sputtered atoms is developed to ascertain the same utilization efficiency in RIMS. About 30% of the atoms sputtered in 1 micros are calculated to be in the laser beam. The atom yield was found to be near unity. The time-gated RIMS useful yield is ~2%. RIMS is used to minimize matrix effects in a depth profile of a Be-implanted AlAs/A1(0.2)Ga(0.8)As heterostructure and shows that Be diffuses from higher Al containing layers at concentrations near 10(19) cm(-3). The atomization of As is shown to be affected by the Al content in a GaAs/Al(0.5)Ga(0.5)As structure. PMID- 20577489 TI - Combined optical second harmonic generation/quartz crystal microbalance study of underpotential deposition processes: copper electrodeposition on polycrystalline gold. AB - Optical second harmonic generation and quartz crystal microbalance techniques are used as in situ probes of copper underpotential deposition on polycrystalline gold surfaces in sulfuric acid electrolyte. The second harmonic signal from a polished bulk gold substrate is observed to decrease by >60% as a result of copper underpotential deposition on gold. Also, the mass of an underpotentially deposited copper adlayer is monitored in situ by an oscillating quartz crystal microbalance, yielding an estimated coverage of ~8.0 x 10(-10) mol cm(-2) and an electrosorption valency of 1.5 for a copper adlayer on the surface of vapor deposited polycrystalline gold. PMID- 20577490 TI - Control of excimer laser aided tissue ablation via laser-induced fluorescence monitoring. AB - Human atherosclerotic arterial samples were ablated via a fiber with a XeCl excimer laser. The resulting tissue fluorescence was recorded for each ablating pulse. The pulse-to-pulse evolution of the fluorescence intensity at 430 nm was obtained and compared to the histological findings. The characteristic transition observed in such curves exhibited good correlation with the transition from the atheromatous layer to the normal media, as determined by the histological examination. The establishment of such a relation led to the development of a simple computer algorithm able to detect plaque to normal media transitions. The limitations of this approach are discussed. PMID- 20577491 TI - Noncontact fluorescence thermometry of acoustically levitated waterdrops. AB - Noncontact thermometry based on the fluorescence excitation spectrum of aqueous Eu(3+) (EDTA) near 579 nm allows us to measure the temperature of an evaporating drop of water. The results for drop diameters in the 500-microm-3-mm range confirm theoretical temperature predictions for steady state evaporation. Calibration of the excitation spectrum in a constant temperature cell indicates that +/-1.0 degrees C resolution is possible for temperatures below 20 degrees C. The spectrum depends only on the solution temperature when Eu(3+) (EDTA) concentrations are below 1 x 10(-3) M and when the solution pH is between 4.0 and 10.0. Excitation spectra from levitated waterdrops contain additional noise which degrades the temperature resolution to +/-1.2 degrees C. With this technique we are able to follow the temperature change in an evaporating drop of water as a monolayer of 1-octadecanol forms on the surface and retards the evaporation. PMID- 20577492 TI - Detection of neutral and ionic reaction mechanisms in molecular clusters. AB - Techniques based on picosecond resonance-enhanced multiphoton ionization and mass selective ion photodissociation are described as a means for studying complex reaction mechanisms in molecular clusters. A set of experiments is described that can identify the cluster-size specific reactions that occur by the overlapping processes of neutral dissociation/fragment ionization, parent ionization/dissociation, and parent ion photoexcitation/dissociation. These molecular beam techniques are demonstrated for the case of neutral and ionic photon transfer and evaporation in clusters of phenol in (NH(3))(n), as well for radical chemistry and van der Waals dissociation in (CH(3)I) (n) clusters. PMID- 20577493 TI - Mapping materials properties with Raman spectroscopy utilizing a 2-D detector. AB - An imaging Raman system based on a 2-D detector and capable of collecting simultaneously 1024 spatially resolved spectra has been constructed. Hardware and software are described which allow real time analysis of the spectral data, leading to a large reduction in the data storage requirements. The analysis yields a 1-D profile (1024 points) across the sample of chemical or physical properties that are distinguishable by their Raman spectral features. Sample translations, along with repeated collection and analysis cycles, allow 2-D maps of chemical or physical properties to be generated rapidly. The spatial resolution and spectral precision are 5microm and 0.16 cm(-1) respectively. Applications to the analysis of phase transformed zones in microengineered zirconias and to measurement of an in situ temperature profile of a single carbon fiber are presented. In a typical application, 66,560 Raman spectra from an 8- x 6-mm area on a partially stabilized zirconia sample were collected and analyzed in 5.4 h to produce a 2-D map of the fraction of tetragonal phase transformed to monoclinic phase during crack propagation. PMID- 20577494 TI - Chemical ionization Fourier transform mass spectrometry of chemical warfare agent simulants using laser-produced metal ions. AB - In an initial investigation of the potential utility of chemical ionization (CI) mass spectrometry of selected analogs of chemical warfare agents using metal ions, the reactions of manganese ions with chloroalkyl sulfides and organophosphonates have been followed in a Fourier transform mass spectrometer. Mn(+) ions, produced by UV laser radiation focused on a stainless steel target, react rapidly with each molecule studied to provide characteristic mass spectra. The manganese ion CI mass spectra are compared to mass spectra obtained via electron impact (EI) and methane CI. PMID- 20577495 TI - Ultraviolet laser microplasma-gas chromatography detector: detection of species specific fragment emission. AB - Characteristic laser-produced microplasma emissions from various simple carbon containing vapors entrained in a He carrier gas have been observed and compared. A focused ArF (193-nm) excimer laser is used to induce microplasmas with modest pulse energies (15 mJ or less) in the effluent region of a gas chromatography capillary column. Strong atomic (C, H, O, Cl, and F) as well as molecular (C(2), CH, and CCI) emissions are observed with very high SNRs. A plasma emission survey indicates that different classes of molecule show unique spectra which make it relatively easy to distinguish one chemical class from another. These results suggest that a laser microplasma gas chromatography detector (LM-GCD) should offer additional discrimination/resolution for unknown sample gas mixture analysis. In addition, the LM-GCD exhibits a significant advantage over certain other GC detectors, like the widely used flame ionization detector, by readily detecting nonresponsive gases such as CO, CO(2), CCl(4) and Freons. PMID- 20577496 TI - Two-photon excited LIF determination of H-atom concentrations near a heated filament in a low pressure H(2)environment. AB - With respect to the investigation of low pressure filament-assisted chemical vapor deposition processes for diamond formation, absolute concentrations of atomic hydrogen were determined by two-photon laserinduced fluorescence in the vicinity of a heated filament in an environment containing H(2) or mixtures of H(2)and CH(4). Radial H concentration profiles were obtained for different pressures and filament temperatures, diameters, and materials. The influence of the addition of various amounts of methane on the H atom concentrations was examined. PMID- 20577497 TI - Optical emission spectrometry and laser-induced fluorescence of laser produced sample plumes. AB - The ablation and atomization process of solid samples into a buffer gas by pulsed laser radiation is discussed and the optimum conditions for elemental analysis by optical emission spectrometry and laser-induced fluorescence (LIF) are described. Pulsed tunable dye lasers are used for LIF measurements. Improved LIF detection limits for some elements are reported. The physical processes which limit the detection of elements in the laser produced sample plume are discussed and theoretical estimates of relative detection limits are compared to the experimental results. Calibrations of LIF data by internal standardization are demonstrated with metallic and borax glass matrices. PMID- 20577498 TI - Operating characteristics of a tunable diode laser absorption spectrometer using short-external-cavity and DFB laser diodes. AB - Second harmonic detection at audio frequencies of isolated absorption lines with a laser absorption spectrometer employing AlGaAs and InGaAsP diode lasers, short external cavity (SXC) AlGaAs and InGaAsP diode lasers, and InGaAsP distributed feedback (DFB) diode lasers was investigated and compared. Noise levels equivalent to line center absorptions of ~3 x 10(-6) were achieved with each source. Single mode tuning ranges of 20-50 cm(-1) were obtained with both the SXC and DFB sources. The contamination of absorption spectra by suppressed laser side modes was identified and investigated as it relates to the identification of weak lines in the presence of strong lines. PMID- 20577499 TI - Patents. AB - 4,852,983; 4,861,124; 4,906,095; 4,907,849; 4,871,220; 4,909,628; 4,869,593; 4,898,470; 4,893,910; 4,915,476; 4,919,527; 4,921,335; 4,925,271; 4,929,063; 4,932,762; 4,938,572; 4,940,309; 4,929,077; 4,932,737; 4,946,233; 4,936,653; 4,939,368; 4,943,146; 4,940,305; 4,945,248; 4,941,719; 4,942,299; 4,946,279; 4,947,034; 4,943,144; 4,940,333; 4,929,050; 4,946,231; 4,947,044; 4,947,400. PMID- 20577501 TI - Of optics and opticists. PMID- 20577500 TI - Nasa patter. PMID- 20577502 TI - Optical linewidth measurements using a polarizing microscope with crossed polarizers. PMID- 20577503 TI - Solar interferometry utilizing the visibility of diffraction-free images. PMID- 20577504 TI - Balloon-borne laser spectrometer measurements of NO(2) with gas absorption sensitivities below 10(-5). PMID- 20577505 TI - Multiple scattering lidar. PMID- 20577506 TI - Infrared propagation within a few meters of the sea surface. PMID- 20577507 TI - Microoptics: introduction by the feature editors. AB - This introduction briefly defines the scope of the feature in this 10 Nov. 1990 issue on microoptics. The first part of the feature, on gradient-index imaging systems, has appeared in the 1 Oct. 1990 issue. All feature papers are based on presentations made at the joint conference MOC/GRIN '89. PMID- 20577508 TI - Optical computing and related microoptic devices. AB - We investigate scaling with the cross-sectional area of energy and speed for optical devices and of optical design, speed, and thermal dissipation for device arrays. Theory and experiments clearly point to lower energy and faster speed for smaller devices and to simpler optical design, smaller propagation time delays, and higher thermal dissipation capability for smaller array sizes. We conclude that the development of high speed digital optical processors will depend on small devices interconnected by microoptic systems. PMID- 20577509 TI - All-optical triode device design using a nonlinear etalon and GRIN lenses. AB - Optical triode characteristics of a nonlinear etalon combined with GRIN lenses are investigated. This configuration facilitates adjustment of detuning by a factor of 10-50 and enables a high on-off ratio operation using a double detuning operation. An optical gate and spatial switches are also fabricated using this configuration. PMID- 20577510 TI - New design for geodesic lenses. AB - A new method of designing geodesic lenses is described. The lens shape is expressed with a uniform function. The curvature of the lens shape is restricted within an upper limit to prevent the light leaking from the waveguide. The value of the curvature limit can be specified at the start of design calculation. A comparison with a former design method is also given. The numerical aperture of the lens is found to be improved up to 24%. PMID- 20577511 TI - Beam propagation method analysis of optical waveguide lenses. AB - Focusing characteristics of optical waveguide lenses are analyzed by the beam propagation method (BPM) instead of the ray tracing method. By use of the BPM, we can observe field distributions of a converging or diverging light beam after it passes through a waveguide lens. Variations of the spot width and magnitude of diffraction can immediately be evaluated with this calculation. The BPM calculations are used for a mode-index, Luneburg, and geodesic lenses. For the application of the method to the geodesic lens, the surface deformation is converted into an equivalent index. PMID- 20577512 TI - Simultaneous measurement of refractive index and thickness of thin film by polarized reflectances. AB - A new technique to obtain the refractive index and thickness of a thin film simultaneously is presented. The reflectances of p-polarized light and s polarized light are measured at various angles of incidence, and by a numerical procedure the film index and thickness are extracted from the measured reflectances. The measurements and numerical procedure are simple, and the values obtained are accurate. As an example, we made measurements on a single layer film (SiO(2)/Si) and a double layer film (SiON/SiO(2)/Si) and confirmed that the values obtained were consistent. PMID- 20577513 TI - Ion beam sputtered (SiO(2))(x)(Si(3)N(4))(1-x) antireflection coatings on laser facets produced using O(2)-N(2) discharges. AB - The chemical composition of a (SiO(2))(x)(Si(3)N(4))(1-x) film produced by ion beam sputtering was precisely controlled by the ratio of O(2) and N(2) flow rates under a discharge current kept constant to within an accuracy of +/-0.05 A. The reproducibility of the refractive index was improved to +/-0.01. This film was applied to form antireflection coatings with extremely low reflectivity on facets of 830-nm AlGaAs double heterostructure lasers. The minimum reflectivity was 6.8 x 10(-5), and a reflectivity of 1 x 10(-4) was achieved reproducibly. Experimental studies show that antireflection coatings are effective for suppressing the interferometric light output variation of composite cavity lasers. PMID- 20577514 TI - Effective reflectivity from self-imaging in a Talbot cavity and its effect on the threshold of a finite 2-D surface emitting laser array. AB - Using a self-imaged diffraction coupled model in a Talbot cavity for vertical cavity surface emitting laser arrays, the effect of self-imaged reflections on the lasing threshold of a finite 2-D array was investigated. Array size and the ratio defined by the element diameter/element spacing were found to affect the effective reflectivity as seen from the laser cavities and, ultimately, the device threshold. A general curve showing the dependence of the 2-D coupling coefficient on the array fill factor and array size has been found. Minimum levels of laser facet reflectivities have been obtained as a function of the array fill factor for practical devices with low threshold current densities. KEYWORDS: 2-D coherent arrays, self-imaging, Talbot effect, laser arrays. PMID- 20577515 TI - Experimental demonstration of optical field evolution in waveguide junctions by using a video camera observing system. AB - We have experimentally proved the optical field evolution in waveguide junctions formed by potassium ion exchange in a glass substrate using a microcomputer assisted video camera observing system. The optical field profiles in various waveguide junctions such as Y- and X-junctions have been clearly observed. Most of the results support the predicted operation of the junctions. PMID- 20577516 TI - MgO/Ti bilaterally diffused LiNbO(3) optical switch. AB - A MgO/Ti bilaterally diffused optical waveguide is proposed. It features controlling the waveguide spot size and strengthening the optical confinement. It is experimentally shown that the coupling loss with single-mode fiber is reduced to 0.6 dB/facet. The bending loss is also suppressed from 2.2 dB of the Ti diffused waveguide to 0.2 dB at a 30-mm bending radius. The performance of the switch using this method is demonstrated. Total insertion loss is 2.6 dB. Driving voltage is 5.6 V with no degradation of the EO effect. PMID- 20577517 TI - Practical method of waveguide-to-fiber connection: direct preparation of waveguide endface by cutting machine and reinforcement using ruby beads. AB - We propose and demonstrate new practical methods of waveguide end fabrication and fiber attachment for Ti:LiNbO(3) waveguides. We fabricated waveguide endfaces with a cutting machine, which simplifies the manufacture of waveguide devices and provides a low excess loss of 0.3 dB or less. Our proposed fiber attachment method features fibers that protrude slightly from the reinforcement. It provides easy alignment, low excess loss (<0.1 dB), high strength (>600 gf), and high thermal stability (-10 to 60 degrees C). We also developed an easy way to reduce the backreflection from the joint without using anti-reflection coating. Instead, a tapered hemispherical end fiber and an angled waveguide endface are used. Backreflection is easily reduced to less than -30. PMID- 20577518 TI - Fabrication of aberration-free focusing grating couplers. AB - An almost aberration-free focusing grating coupler with a grating area of 1 x 1 mm(2) and a 2-mm focal length was made by using an electron beam writing system with accurately calibrated electron beam deflection and an accurate parameter setting of the effective refractive index of the waveguide. The smallest focused spot size achieved was 1.2 microm (FWHM), which is 1.06 times the value of the diffraction-limited spot size. PMID- 20577519 TI - ZnS micro-Fresnel lens and its uses. AB - A micro-Fresnel lens replication method by inorganic material deposition has been developed. A ZnS micro-Fresnel lens and a completely flat micro-Fresnel lens have been made by this method. The ZnS microFresnel lens stability characteristics are improved for temperature, humidity, and focusing. Furthermore, higher resolution in electron-beam lithography is made possible by lens thickness reduction. The completely flat micro-Fresnel lens is a new device and improves integration performance. This lens can be applied to stacked planar optics devices for use in the construction of 3-D optical circuits. PMID- 20577520 TI - Fabrication of holographic microlenses using a deep UV lithographed zone plate. AB - Holographic microlens arrays and elliptical zone plates are fabricated on holographic plates and photoresists by interference between the first- and second order diffracted waves from an ion etched Fresnel zone plate, which is made by electron-beam scanning and deep UV lithography. This method of fabrication is simple, and a holographic lens with a large numerical aperture and short focal length is obtained. Experimental results of focusing and imaging by a lens array and an elliptical zone plate are given. Two methods of fabricating holographic zone plates for an IR or UV wavelength are also proposed. PMID- 20577521 TI - Efficient zone plate array accessor for optoelectronic integrated circuits: design and fabrication. AB - A spatially divided beam splitter is designed, by which the laser diode light couples into multiple fibers using a cylindrical lens and a phase type linear zone plate array. Using skew ray tracing, the focusing characteristics of a spatially divided beam splitter are predicted. A three-section linear zone plate array with the linewidth changing from 1.1 to 2.05 microm was fabricated by holographic mask patterning and deep UV printing. In oblique incident conditions close to the Bragg angle, the diffraction efficiency reached 60%. By combining the linear zone plate array with a cylindrical lens, simultaneous focusing and separation of the laser output are achieved. PMID- 20577522 TI - Laser beam lithographed micro-Fresnel lenses. AB - Laser beam lithography for micro-Fresnel lenses (MFLs) with blazed grooves is proposed and demonstrated including the system configuration and characteristics of the resulting lenses. The resolution is even better than that of electron-beam lithography in forming 1-microm deep relief gratings in resist. A laser beam lithographed MFL with a diameter as large as 9.6 mm is described as well as a compact MFL (N.A. 0.21) butt coupled to an optical waveguide. In these two distinct MFLs, nearly diffraction-limited spot sizes have been obtained with diffraction efficiencies of 50% or more. A specific MFL array used for an integrated optic laser Doppler velocimeter is also presented. PMID- 20577523 TI - Holographic optical element for an optical disk head with spot-size detection servo optics. AB - A CGH construction of a holographic optical element (HOE) for an optical disk head with spot-size detection by means of superimposing two Fresnel zone plates is studied. Optimum parameter values for the ratio of segment to grating pitch (duty) and grating height are clarified from the viewpoint of total light power efficiency in the round trip optical system. The influences of higher-order diffracted beams near the first-order diffracted beams used to get signals on signal detection are shown to be small. The HOEs with almost optimum parameter values are fabricated and the desired diffracted spots, the expected total light power efficiency, and the small influence of higher-order diffracted beams are observed. PMID- 20577524 TI - Reflection polarizing holographic optical element for compact magnetooptical disk heads. AB - A reflection polarizing holographic optical element with sinusoidal surface relief has been developed for compact magnetooptical (MO) disk heads. The element has the polarizing beam splitter function as well as the focusing and tracking error signal detection functions. To produce the sinusoidal surface-relief structure with photolithography, a new fabrication process, which includes procedures for converting a rectangular profile into a sinusoidal profile, is introduced. Replicas were also fabricated with high replication fidelity using the photopolymerization method. The developed element was used in an MO disk head. A 57-dB C/N ratio, which is sufficient value for practical use was achieved for a 1-MHz readout signal. PMID- 20577525 TI - Use of heterodyne detection to measure optical transmittance over a wide range. AB - We are developing a heterodyne detection technique to measure optical transmittance with high accuracy over an unprecedented dynamic range. We have measured filters spanning a wide range of transmittances (12 orders of magnitude) and have evaluated the absolute uncertainties and discuss the ultimate accuracies that may be achieved. Our setup uses a two-beam Mach-Zehnder interferometer with acoustooptic frequency shifting to produce a frequency difference between the two light beams. We determine the optical transmittance of a filter by inserting it into one of the interferometer arms and measuring the change in amplitude of the signal at the difference frequency on the interferometer output beam. This method allows direct comparisons between optical and rf attenuators, ultimately tying optical transmittance measurements to rf attenuation standards in an absolute way. PMID- 20577526 TI - Light emission from a titanium vacuum arc using Fizeau interferometry with parallel detection. AB - The lineshape of light emission from a titanium vacuum arc was studied using a Fizeau interferometer coupled with an optical multichannel analyzer (OMA). A viewing geometry normal to the cathode surface was employed. Temperatures of ~3 x 10(5) K and ~3.5 x 10(4) K were obtained for titanium ions and titanium atoms present in the cathode spot, respectively. In light of results from previous work, a case is made for the latter temperature being the actual heavy species temperature in the cathode spot. PMID- 20577527 TI - Testing a zone plate with a grating interferometer. AB - The physical theory, of testing optics by the Ronchi sine grating interferometer is developed. In the experiment a sine grating splits the third-order wavefront of the zone plate under test into three displaced wavefronts, which then interfere with one another to form interference fringes. The intensity distribution of the interference pattern can be recorded for various positions of the sine grating. By subtracting the contribution of the inherent diffractive aberration of the sine grating, the value of the spherical aberration associated with the third-order wavefront of the zone plate under test can be determined. Theory and experiment are compared. PMID- 20577528 TI - Real time interferometric ellipsometry with optical heterodyne and phase lock-in techniques. AB - In this paper, we have combined a Mach-Zehnder interferometer and an optical heterodyne using an AO modulator to set up an interferometric ellipsometer for measuring the optical properties of metal surfaces. Because there is no moving mechanism, e.g., compensators and quarterwave plates, we can eliminate the errors caused by these elements. By using a phase lock-in technique and computer processing, we can measure parameters Psi and Delta in real time and with great accuracy (where Psi is the amplitude ratio of the P- and S-waves, and Delta is the phase difference in the P- and S-waves). PMID- 20577529 TI - Microscopic mapping of subnanometric motion. AB - The sensitivity of a microscope-based holographic system designed for mapping the motion of components of a living cell is calibrated by means of a simple procedure. Bubbles of air are allowed to drift with known velocity in a nearly horizontal, glycerine-filled capillary observed through the microscope. The ultrafine motion of the bubbles is captured interferometrically by subtractive superposition of a pair of holograms recorded a few milliseconds apart. Stationary portions of the field of view are rendered dimly in images reconstructed from the interferogram, while the brightness of moving portions varies monotonically with their displacement. Displacements as small as 1.1 nm were betrayed in the images. Analysis of the experimental conditions suggests that bubble displacements as small as 0.7 nm will become detectable once minor improvements are made in the apparatus. PMID- 20577530 TI - Fiber optic Fourier transform spectrometer with a coherent interferogram averaging scheme. AB - A fiber optic Fourier transform spectrometer capable of coherent interferogram averaging is constructed, for the first time to our knowledge. One fiber arm of the interferometer is periodically stretched, and the amplitudes of the fundamental and second harmonics of the modulation frequency in the photocurrent output are simultaneously detected. Successful operation results from the generation of an external clock for sampling the interferogram from the detected outputs varying in phase quadrature. Even when the moving mirror in the interferometer translates nonlinearly and two fiber arms receive random perturbations independently, sampling can be uniformly performed along the interferogram. From the experiments, variation of sampling start position on each interferogram was limited within 100 nm during one hundred repetitive scans. For 100 coherent averages, therefore, the SNR increased by ~10 without deformation. PMID- 20577531 TI - Impact of atmospheric layering on LOWTRAN 6 radiance calculations. AB - Measurements of 8-12-microm near-horizon sky radiances and meteorological parameters over the ocean near San Diego, CA, were used to evaluate the sky radiance algorithm of LOWTRAN 6. Discrepancies in measured and calculated sky radiances previously attributed to the neglect of multiple scattering effects of aerosols can be overcome by introducing additional low level layers in the calculations of LOWTRAN 6. A comparison between radiance calculations using the single scattering, additive layer approach and those using a multiple scattering version of LOWTRAN raises questions about the applicability of the multiple scattering approach in the far infrared region. PMID- 20577532 TI - Stratosphere temperature measurement using Raman lidar. AB - Temperature measurements using vibrational Raman scattering from molecular nitrogen were performed simultaneously with temperature obtained by Rayleigh scattering in the amplitude range between 12 and 30 km. The downward extension of the Rayleigh temperature described in this paper leads to the possibility of obtaining a continuous temperature profile from 12 to nearly 100 km. The temperature profiles have been obtained using an instrument made up basically as a Rayleigh lidar with an extra channel. The measurements are in close agreement with the CIRA model and simultaneous balloon sounding. PMID- 20577533 TI - Color characteristic design for color scanners. AB - We propose a method of quantitative color characteristic design for color scanners. We used calorimetric simulation with an optical model and a color conversion circuit to match the scanner color characteristic to an objective color standard. A compensation matrix is defined using the least-squares method to minimize the average error for many colors. To determine the matrix, a color space must be selected. We compared the results of conversion using matrices obtained in the CIELAB color space and in the RGB color space. The comparison shows that both conversions are nearly the same. Using computer simulation, we designed a color scanner with excellent conversion performance. The average color difference for 440 colors was ~1.3. PMID- 20577534 TI - Heterodyne polarimetry technique for complete amplitude scattering matrix for radiation. AB - The phases and amplitudes of all the elements of the scattering matrix for radiation scattered by microparticles are shown to be measurable by a technique which was inspired by the phase differential scattering method developed by Johnston et al. of the Experimental Pathology Group at the Los Alamos National Laboratory. The present method synthesizes a laser beam from a superposition of two coherent beams in which a small frequency offset between perpendicular polarization components has been acoustooptically introduced. The heterodyne signal in the scattered radiation is used to detect the polarimetric null obtained by a variable phase compensator and linear polarizer placed in front of the scattered intensity detector. The reciprocity theorem is used to obtain a complementary set of data to completely determine all the elements of the matrix. PMID- 20577535 TI - Holographic optical elements used in spectroscopy: some remarks on image quality. AB - Because of their significant chromatic aberration, holographic optical elements (HOEs) can be used as narrowband optical filters or scanning spectroscopes. Although it is impossible to obtain aberration free imaging over the whole spectrum of light wavelength, by an appropriate choice of HOE recording and imaging geometries, the aberrations can be seriously minimized. As an example, the imaging quality of several different HOEs used in multichannel spectroscopy is analyzed with the aid of numerical evaluation of the respective diffraction integrals. Such computer modeling of imaging gives more adequate results than the geometric ray tracing method. PMID- 20577536 TI - Coherent detection of optically carried microwave signals through two-wave mixing in a BaTiO(3) crystal. PMID- 20577538 TI - Of optics and opticists. PMID- 20577537 TI - Patents. AB - 4,865,449; 4,930,878; 4,902,100; 4,925,260; 4,927,220; 4,930,868; 4,930,847; 4,921,336. PMID- 20577539 TI - Silicon VLSI/ferroelectric liquid crystal technology for micropower optoelectronic computing devices. PMID- 20577540 TI - Compact optical neural network using cascaded liquid crystal television. PMID- 20577542 TI - Two-dimensional optical Clos interconnection network and its uses: comments. PMID- 20577541 TI - Practical realizations of N(4) optical interconnects. PMID- 20577543 TI - Phase-only filters codified with Burckhardt's method. PMID- 20577544 TI - Mapping considerations for optimal binary correlation filters. AB - The optimality of correlation filters is an important issue in applications of pattern recognition. We consider here both binary phase-only filters (BPOFs) and amplitude encoded binary phase-only filters (AE BPOFs) and study the results of optimizing the filters for a real world object (the Space Shuttle). We find that while only small improvements result from optimizing a BPOF, optimization of the AE BPOF is quite important in obtaining a useful correlation function. In the case of an AE BPOF, both signal-to-noise and peak-to-sidelobe measures must be studied. Computer simulation and experimental correlation results are presented. PMID- 20577545 TI - Polarization-encoded optical shadow casting: design of trinary multipliers. AB - The polarization-encoded optical shadow casting (POSC) scheme is used to design a 2-digit by 2-digit trinary multiplier. Three design algorithms for identifying the appropriate source patterns, input patterns, and output mask for both serial and parallel operations are presented. The inclusion of analyzer pattern reduces the number of pixel subcells for the POSC inputs. PMID- 20577546 TI - Alignability of optical interconnects. AB - Successful development, fabrication, and deployment of optical interconnects and computing systems depend on how easily the optical components and light beams can be aligned. An interconnection system difficult or time-consuming to align is costly to develop and may be unreliable. In this paper a probability theoretical framework is developed for analyzing the alignability, that is, the degree of difficulty of aligning the devices and the light beams, of a given optical interconnection system. The alignability measure is related to the other performance measures of an interconnect such as the power transfer efficiency, SNR, and the spatial and temporal bandwidths. The cost of the development and deployment of an optical processor or interconnection system can be estimated from knowledge of the alignability. PMID- 20577547 TI - Distortion-free imaging through inhomogeneities by selective spatial filtering. AB - Distortion-free imaging through a system with aberrations is possible for a certain class of input. The input spatial spectrum must be restricted to spatial frequencies which are equally affected by the aberrations (i.e., which experience identical phase shifts mod2pi). We demonstrate experimentally that if the aberrations can be localized in the pupil plane, an arbitrary input can be prefiltered to produce a distribution which is imaged without distortion by an aberrant system. Equivalently, the output of the system can be postfiltered to select the information which was imaged without distortion. PMID- 20577548 TI - Multistability, chains, and cycles in optical multiwave mixing processes. AB - We exhibit the information processing capabilities of the first few terms that arise in the amplitude expansion for resonant scattering in a medium with a delay nonlinearity (generalized volume hologram). We begin by showing how the physics of intensity dependent charge transport near a two-photon resonance gives both delayed quadratic and quartic nonlinearities. After reviewing the utility for matrix associative memories exhibited by the delayed quadratic nonlinearity (the ordinary Gabor hologram), we examine the role of the quartic nonlinearity, which is a fourth rank tensor. The symmetries of this tensor determine the information processing capabilities (via multilinear correlations) of the medium in an optical computing paradigm. We find multiple basins of stability, Jordan strings, and cycles as possible dynamic behaviors for the medium. We indicate how each corresponds to an information processing task: multiple basins to multiassociative memory, Jordan strings and cycles to chain and sequence memory and to group-invariant pattern recognition. We briefly indicate how branching processes may be implemented by the fourth rank mode-coupling tensor. PMID- 20577549 TI - Particle image fields and partial coherence. AB - The accuracy of Young's fringe method for reducing velocity field data is compromised by a spatially incoherent background field which originates in the random locations of the seeding particles. The probability density function for the spatial frequency cutoff of this background is derived as a function of the particle count, the distribution governing the power in each frequency interval is derived, and conditions are found under which the Van Cittert-Zernike theorem applies. The background field resembles the far field of a partially coherent source in the high particle count limit, but departs significantly at low and moderate counts. PMID- 20577550 TI - Dichromated gelatin holograms: an investigation of their environmental stability. AB - An investigation of the stability of the diffraction efficiency of dichromated gelatin (DCG) holograms has been carried out paying specific attention to coated and baked holograms that are subsequently exposed to high humidity (RH > 60%) environment. The investigation has revealed that (a) the environmental stability of DCG holograms can be considerably improved either by coating or baking; (b) the DCG holograms can be used at temperatures well-above room temperature (for example, as high as 175 degrees C) without showing undue detrimental effects regarding their efficiency; and (c) the diffraction efficiency of uncoated and baked holograms can be restored by reprocessing whereas such a thing becomes impossible in coated holograms. PMID- 20577551 TI - Image processing for laser speckle velocimetry using the 2-D fast Fourier transform. AB - An algorithm is described for the fringe analysis in laser speckle velocimetry. Based on the 2-D fast Fourier transform, the method relies on inherent features in the fringe pattern to remove efficiently the influence of the diffraction halo. A windowing operation is performed to enhance the reliability and reduce the influence of various noise contributions. PMID- 20577552 TI - Of optics and opticists. PMID- 20577553 TI - Analyzing integrated optical waveguides: a comparison of two new methods. AB - We present a comparison of two recently developed methods of analyzing optical waveguides. One of them is numerical, and the other is an approximate analytical method. PMID- 20577554 TI - Transient gratings in dichromated sugar solutions. AB - In this Technical Note we present the results when dichromated sugar solutions were used to record interference patterns. Transient behavior was noticed. PMID- 20577555 TI - Experimental considerations for 2-D acoustooptic spectrum analysis. AB - A 2-D acoustooptic spectrum analyzer with the associated reference function generator and real-time image processor has been constructed. The operation of the analyzer and the experimental considerations for obtaining a high resolution spectrum in real time are described. PMID- 20577557 TI - Single-beam interferometry of a thermal bump. AB - A novel single-beam interferometric measurement of a thermal bump produced by an intensity modulated and focused laser beam is described. The effects of the ac change in optical reflectivity and the displacement of the surface are determined independently by fitting data to a phenomenological theory. This technique is insensitive to sample vibrations and variations in optical path resulting from thermal fluctuations. PMID- 20577556 TI - Effects of beam focusing on the efficiency of planar waveguide grating couplers. AB - Results of a theoretical and experimental investigation into the variation of coupling efficiency with coupling angle are presented for various beam focusing conditions for an integrated optical grating coupler. This investigation shows that the acceptance angle of the grating coupler can be broadened, within a relatively large range and with a relatively small loss of coupling efficiency, by focusing the incident laser beam. PMID- 20577558 TI - Fiber optic dynamic light scattering from concentrated dispersions. 3: Particle sizing in concentrates. AB - We describe measurements of particle size during the course of a latex emulsion polymerization reaction using fiber optic dynamic light scattering (FODLS). These measurements are compared to results from dynamic light scattering (DLS) measurements performed in the usual way on diluted samples. It is shown that the FODLS measurements follow the DLS results and reliably track the growth of the latex particles throughout the reaction. It thus appears that the FODLS technique is useful for the measurement of particle size in highly concentrated samples, such as is found in latex production. PMID- 20577559 TI - Polarization characteristics of double-clad elliptical fibers. AB - A scalar variational analysis based on a Gaussian approximation of the fundamental mode of a double-clad elliptical fiber with a depressed inner cladding is studied. The polarization properties and graphic results are presented; they are given in terms of three parameters: the ratio of the major axis to the minor axis of the core, the ratio of the inner cladding major axis to the core major axis, and the difference between the core index and the inner cladding index. The variations of both the spot size and the field intensity with core ellipticity are examined. It is shown that high birefringence and dispersion free orthogonal polarization modes can be obtained within the single-mode region and that the field intensity distribution may be more confined to the fiber center than in a single-clad elliptical fiber. PMID- 20577560 TI - Dispersion studies of a single-mode triangular-index fiber with a trench by the vector mode analysis. AB - A Runge-Kutta procedure was used for investigating the dispersion characteristics of single-mode triangular-index fibers with a trench in the cladding. Numerical results on the total dispersion, its sensitivities to the core radius, wavelength, index difference variations, and its influence on the fiber's bandwidth-length product are presented. Some interesting features, due to the presence of a trench, are pointed out. One salient feature is the appearance of dispersion flattening over a certain wavelength range near 1.55 microm for b/a = 2 and c/a > 2.7 (a = core radius, b = inner trench radius, c = outer trench radius) where the total dispersion is low, yielding a bandwidth-length product as high as 10(4) GHz . km. The presence of a trench has not been investigated previously. PMID- 20577561 TI - Hardware-compressive 2-D fiber optic delay line architecture for time steering of phased-array antennas. AB - The requirements for true time steering of phased array antennas are reviewed, and the resulting delay line hardware requirements are discussed. Two hardware compressive fiber optic delay line architectures are then briefly described and quantitatively compared. The basics of phased array antenna partition are then presented. Based on these principles a delay-compressive and element-compressive 2-D fiber optic delay line architecture is described, and its basic characteristics and capabilities are discussed. PMID- 20577562 TI - Passive fiber optic gyroscope. AB - A fiber optic gyroscope different from the standard concept is presented. A fused fiber 3 x 3 directional coupler provides a constant phase shift thus enabling the detection of rotation rate at the quadrature point without phase modulation. Bias errors due to birefringent coupling centers in the fiber coil are avoided by using an unpolarized light source. A contrast insensitive signal recovery scheme eliminates the influence of polarization fluctuations on the scale factor. First measurements with a prototype gyroscope (90 mm in diameter and 23 mm in height) show a bias stability of <4.7 degrees /h and scale factor accuracy of <0.1% in the range of +/-200 degrees /s. PMID- 20577563 TI - Diode laser measurements of Kr-broadened linewidths in the nu(1) band of OCS. AB - Kr-broadened halfwidths of twenty-eight lines in the nu(1) band of OC(32)S have been measured from absorption spectra recorded at room temperature with a tunable diode laser spectrometer. The results are compared to values calculated on the basis of the Anderson-Tsao-Curnutte theory and an improved semiclassical impact model developed by Robert and Bonamy. Both theories have been applied from a Smith-Giraud-Cooper intermolecular potential by considering the potential coefficients as adjustable parameters. Moreover, an atom-atom interaction model was used in the latter theory. PMID- 20577564 TI - Pulse compression and traveling wave excitation scheme using a single dispersive element. AB - A single dispersive element is shown to be sufficient for simultaneous pulse compression and tilting of the pulse front, and therefore well-suited for traveling-wave excitation of targets. It is shown that in all the previous arrangements used for traveling wave excitation, spatially dependent group velocity dispersion occurs along the target. A compensated arrangement is proposed that provides pulse compression at the target-plane and exact synchronism between the pump and the generated pulses for various targets. PMID- 20577565 TI - Controlled lens formation with unapertured excimer lasers: use with organic polymers and corneal tissues. AB - A theoretical model is developed which allows for well-defined lenses to be formed with different dioptric properties using lasers that are known to ablate a variety of materials. With the theoretical development as a guide an experimental arrangement is defined for the ArF excimer laser and this arrangement is used to form lenses with highly smooth surfaces in three polymeric materials (polymethyl methacrylate, polycarbonate, and polyvinyl chloride) to test the validity of the theory. As part of the procedure to obtain these lenses, ablation curves (etch depth per pulse vs log of the laser fluence) were measured for each of these polymers and these curves are also reported. The experiments were extended to the rabbit cornea in which the corneal button was reshaped as part of keratomileusis surgery. This preliminary experiment resulted in a clear cornea with a smooth corneal surface and a measured change of 3 diopters in the treated eye. PMID- 20577566 TI - Lasing and stimulated Raman scattering in spherical liquid droplets: time, irradiance, and wavelength dependence. AB - Measurement of lasing from dye doped micron sized ethanol droplets irradiated by a pulsed Nd:YAG laser shows evidence of lifetime broadening and relaxation oscillations. Observations of stimulated Raman scattering (SRS) and lasing generated by the same laser pulse in a dye doped ethanol droplet and coupled to the same morphology dependent resonance exhibit longer delays in the initiation of SRS than for pure ethanol droplets where lasing is absent. SRS emission above the plasma breakdown threshold is not measurably delayed and is quenched by the developing plasma. PMID- 20577567 TI - Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. AB - Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders. PMID- 20577568 TI - Microwave-assisted sequential one-pot protocol to benzothiadiazin-3-one-1,1 dioxides via a copper-catalyzed N-arylation strategy. AB - A microwave-assisted, sequential, one-pot protocol has been developed for the synthesis of a variety of benzothiadiazin-3-one-1,1-dioxides. This protocol utilizes a copper-catalyzed N-arylation of alpha-bromo-benzenesulfonamides with a number of amines to generate the corresponding 2-aminobenzenesulfonamides, which undergo cyclization to the desired sultams using carbonyl diimidazole (CDI). A range of conditions was evaluated for the key C-N bond formation step with tolerance toward functionalized amines. PMID- 20577569 TI - Unraveling human complexity and disease with systems biology and personalized medicine. AB - We are all perplexed that current medical practice often appears maladroit in curing our individual illnesses or disease. However, as is often the case, a lack of understanding, tools and technologies are the root cause of such situations. Human individuality is an often-quoted term but, in the context of human biology, it is poorly understood. This is compounded when there is a need to consider the variability of human populations. In the case of the former, it is possible to quantify human complexity as determined by the 35,000 genes of the human genome, the 1-10 million proteins (including antibodies) and the 2000-3000 metabolites of the human metabolome. Human variability is much more difficult to assess, since many of the variables, such as the definition of race, are not even clearly agreed on. In order to accommodate human complexity, variability and its influence on health and disease, it is necessary to undertake a systematic approach. In the past decade, the emergence of analytical platforms and bioinformatics tools has led to the development of systems biology. Such an approach offers enormous potential in defining key pathways and networks involved in optimal human health, as well as disease onset, progression and treatment. The tools and technologies now available in systems biology analyses offer exciting opportunities to exploit the emerging areas of personalized medicine. In this article, we discuss the current status of human complexity, and how systems biology and personalized medicine can impact at the individual and population level. PMID- 20577570 TI - An Evaluation of Solution Algorithms and Numerical Approximation Methods for Modeling an Ion Exchange Process. AB - The focus of this work is on the modeling of an ion exchange process that occurs in drinking water treatment applications. The model formulation consists of a two scale model in which a set of microscale diffusion equations representing ion exchange resin particles that vary in size and age are coupled through a boundary condition with a macroscopic ordinary differential equation (ODE), which represents the concentration of a species in a well-mixed reactor. We introduce a new age-averaged model (AAM) that averages all ion exchange particle ages for a given size particle to avoid the expensive Monte-Carlo simulation associated with previous modeling applications. We discuss two different numerical schemes to approximate both the original Monte Carlo algorithm and the new AAM for this two scale problem. The first scheme is based on the finite element formulation in space coupled with an existing backward-difference-formula-based ODE solver in time. The second scheme uses an integral equation based Krylov deferred correction (KDC) method and a fast elliptic solver (FES) for the resulting elliptic equations. Numerical results are presented to validate the new AAM algorithm, which is also shown to be more computationally efficient than the original Monte Carlo algorithm. We also demonstrate that the higher order KDC scheme is more efficient than the traditional finite element solution approach and this advantage becomes increasingly important as the desired accuracy of the solution increases. We also discuss issues of smoothness, which affect the efficiency of the KDC-FES approach, and outline additional algorithmic changes that would further improve the efficiency of these developing methods for a wide range of applications. PMID- 20577571 TI - Oxford House Recovery Homes: Characteristics and Effectiveness. AB - One of the largest examples of a community-based, mutual-help residential community for high risk substance abuse individuals is Oxford House. In the U.S., over 9,800 people live in these self-run dwellings where they obtain jobs, pay utility bills, and learn to be responsible citizens. Beginning with one single rented residence in the mid 1970s, Oxford Houses now number over 1,300. These rented homes are helping to deal with drug addiction and community re-entry by providing stable housing without any limits on length of stay, a network of job opportunities, and support for abstinence. An exploration of the research on these unique settings highlights the strengths of such a community-based approach to addressing addiction. New roles for psychologists in working with these types of support systems are identified. PMID- 20577572 TI - Emergency Cardiac Biomarkers and Point-of-Care Testing: Optimizing Acute Coronary Syndrome Care Using Small-World Networks In Rural Settings. PMID- 20577573 TI - Specification and Estimation of Spatial Autoregressive Models with Autoregressive and Heteroskedastic Disturbances. AB - This study develops a methodology of inference for a widely used Cliff-Ord type spatial model containing spatial lags in the dependent variable, exogenous variables, and the disturbance terms, while allowing for unknown heteroskedasticity in the innovations. We first generalize the GMM estimator suggested in Kelejian and Prucha (1998,1999) for the spatial autoregressive parameter in the disturbance process. We also define IV estimators for the regression parameters of the model and give results concerning the joint asymptotic distribution of those estimators and the GMM estimator. Much of the theory is kept general to cover a wide range of settings. PMID- 20577575 TI - Posttranscriptional Regulation of Cyclooxygenase 2 Expression in Colorectal Cancer. AB - Cyclooxygenase (COX)-2 enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states, and overexpression of COX-2 occurs at multiple stages of colon carcinogenesis, allowing elevated prostaglandin synthesis to occur in the tumor microenvironment. In normal cells, COX-2 expression levels are potently regulated at the posttranscriptional level through various RNA sequence elements present within the mRNA 3' untranslated region (3'UTR). A conserved AU rich element functions to target COX-2 mRNA for rapid decay and translational inhibition through association with various RNA-binding proteins to influence the fate of COX-2 mRNA. The 3'UTR contains alternative polyadenylation signals that result in a shortened 3'UTR and loss of regulatory elements. Specific microRNAs have been identified to bind regions within the COX-2 3'UTR and control COX-2 expression. Recent evidence demonstrates the functional significance of the COX-2 3'UTR and how improper recognition of the 3'UTR can contribute to COX-2 overexpression in colorectal cancer. PMID- 20577576 TI - Fast Track intervention effects on youth arrests and delinquency. AB - This paper examines the effects of the Fast Track preventive intervention on youth arrests and self-reported delinquent behavior through age 19. High-risk youth randomly assigned to receive a long-term, comprehensive preventive intervention from 1st grade through 10th grade at four sites were compared to high-risk control youth. Findings indicated that random assignment to Fast Track reduced court-recorded juvenile arrest activity based on a severity weighted sum of juvenile arrests. Supplementary analyses revealed an intervention effect on the reduction in the number of court-recorded moderate-severity juvenile arrests, relative to control children. In addition, among youth with higher initial behavioral risk, the intervention reduced the number of high-severity adult arrests relative to the control youth. Survival analyses examining the onset of arrests and delinquent behavior revealed a similar pattern of findings. Intervention decreased the probability of any juvenile arrest among intervention youth not previously arrested. In addition, intervention decreased the probability of a self-reported high-severity offense among youth with no previous self-reported high-severity offense. Intervention effects were also evident on the onset of high-severity court-recorded adult arrests among participants, but these effects varied by site. The current findings suggest that comprehensive preventive intervention can prevent juvenile arrest rates, although the presence and nature of intervention effects differs by outcome. PMID- 20577574 TI - Advancements in gene transfer-based therapy for hemophilia A. AB - Gene therapy has promised clinical benefit to those suffering with hemophilia A, but this benefit has not yet been realized. However, during the past two decades, basic and applied gene therapy research has progressed and the goal of gene therapy for hemophilia A is once again in our sights. The hemophilia A patient population suffers from a disease that requires invasive, lifelong management, is exorbitantly expensive to treat, has geographically limited treatment access and can become untreatable due to immune reactions to the treatment product. Subsequent to the cloning of the factor VIII gene and cDNA in the early 1980s, academic and commercial research laboratories began to pursue gene transfer-based therapies to supplement or supplant the available protein replacement therapy. However, to date, clinical trials for gene therapy of hemophilia A have been unsuccessful. Three trials have been conducted with each having tested a different gene-transfer strategy and each demonstrating that there is a considerable barrier to achieving sustained expression of therapeutic amounts of factor VIII. Recent progress has been made in gene-transfer technology and, relevant to hemophilia A, towards increasing the biosynthetic efficiency of factor VIII. These advances are now being combined to develop novel strategies to treat and possibly cure hemophilia A. PMID- 20577577 TI - Enhanced Delivery of Erythropoietin Across the Blood-Brain Barrier for Neuroprotection against Ischemic Neuronal Injury. AB - Due to limited penetration of the BBB, many therapeutic agents in clinical use require higher doses in order to reach effective concentrations in brain. In some instances, these high doses elicit severe side effects. In the case of erythropoietin (EPO), an established neuroprotectant against ischemic brain injury, its low BBB permeability requires such a high therapeutic dose that it can induce dangerous complications such as polycythmia and secondary stroke. The purpose of this study is to generate a modified EPO that has increased facility crossing the BBB without losing its neuroprotective element. We have engineered a fusion protein (EPO-TAT) by tagging a protein transduction domain derived from HIV TAT to the EPO protein. This sequence enhanced the capacity of EPO to cross the BBB in animals at least twofold when IP administered and up to five-fold when IV administered. In vitro experiments showed that this EPO fusion protein retained all its protective properties against neuronal death elicited by oxygen glucose deprivation and NMDA insults. The needed therapeutic dose of the EPO-TAT was decreased by ~10-fold compared to that of regular EPO to achieve equivalent neuroprotection in terms of reducing volume of infarction induced by middle cerebral artery occlusion in mice. Our results support the approach of using a protein transduction domain coupled to therapeutic agents. In this way, not only can the therapeutic doses be lowered, but agents without BBB permeability may now be available for clinical applications. PMID- 20577579 TI - A Convenient Synthetic Route to Furan Esters and Lactones by Palladium-Catalyzed Carboalkoxylation or Cyclocarbonylation of Hydroxyl-Substituted 3-Iodofurans. AB - An effective palladium-catalyzed protocol for the intermolecular carboalkoxylation or intramolecular cyclocarbonylation of hydroxyl-substituted 3 iodofurans under carbon monoxide pressure has been developed. The 3-iodofurans are readily prepared by iodocyclization of 2-(1-alkynyl)-2-alken-1-ones in the presence of various diols. PMID- 20577578 TI - Molecular modeling and dynamics studies with explicit inclusion of electronic polarizability. Theory and applications. AB - A current emphasis in empirical force fields is on the development of potential functions that explicitly treat electronic polarizability. In the present article, the commonly used methodologies for modelling electronic polarization are presented along with an overview of selected application studies. Models presented include induced point-dipoles, classical Drude oscillators, and fluctuating charge methods. The theoretical background of each method is followed by an introduction to extended Langrangian integrators required for computationally tractable molecular dynamics simulations using polarizable force fields. The remainder of the review focuses on application studies using these methods. Emphasis is placed on water models, for which numerous examples exist, with a more thorough discussion presented on the recently published models associated with the Drude-based CHARMM and the AMOEBA force fields. The utility of polarizable models for the study of ion solvation is then presented followed by an overview of studies of small molecules (e.g. CCl(4), alkanes, etc) and macromolecule (proteins, nucleic acids and lipid bilayers) application studies. The review is written with the goal of providing a general overview of the current status of the field and to facilitate future application and developments. PMID- 20577580 TI - A GENERAL ASYMPTOTIC THEORY FOR MAXIMUM LIKELIHOOD ESTIMATION IN SEMIPARAMETRIC REGRESSION MODELS WITH CENSORED DATA. AB - We establish a general asymptotic theory for nonparametric maximum likelihood estimation in semiparametric regression models with right censored data. We identify a set of regularity conditions under which the nonparametric maximum likelihood estimators are consistent, asymptotically normal, and asymptotically efficient with a covariance matrix that can be consistently estimated by the inverse information matrix or the profile likelihood method. The general theory allows one to obtain the desired asymptotic properties of the nonparametric maximum likelihood estimators for any specific problem by verifying a set of conditions rather than by proving technical results from first principles. We demonstrate the usefulness of this powerful theory through a variety of examples. PMID- 20577581 TI - Fluorescence Sensing of Zinc and Mercury Ions with Hydrophilic 1,2,3-Triazolyl Fluorene Probes. AB - The ability to rapidly detect biologically and environmentally significant metal ions such as zinc and mercury is important to study a number of important cellular and environmental processes. Hydrophilic bis(1,2,3-triazolyl)fluorene based derivatives, containing a 1,2,3-triazole-based recognition moiety, were synthesized through Click chemistry and characterized by UV-vis absorption, fluorescence emission, and two-photon absorption as new fluorescence sensing probes, selective for Zn(2+) and Hg(2+) ions. The UV-vis absorption and fluorescence emission spectra of the complexes exhibited blue-shifted absorption and emission spectra upon chelation to Zn(2+) and Hg(2+) ions, resulting in ca. two-fold enhancement in fluorescence. Fluorometric titration revealed that 1:2 and 1:3 ligand to metal complexes formed with binding constants of 10(8) and 10(16) for Zn(2+) and Hg(2+), respectively. The two-photon absorption cross sections for the probes and probe-metal ion complexes ranged from 200-350 GM at 800 nm. These novel fluorescent compounds may have potential as new metal ion sensors to probe cellular and biological environments. PMID- 20577582 TI - The ABC's of LGM: An Introductory Guide to Latent Variable Growth Curve Modeling. AB - In recent years, we have witnessed an increase in the complexity of theoretical models that attempt to explain behavior from both contextual and developmental perspectives. This increase in the complexity of our theoretical propositions regarding behavior parallels recent methodological advances for the analysis of change.These new analysis techniques have fundamentally altered how we conceptualize and study change. Researchers have begun to identify larger frameworks to integrate our knowledge regarding the analysis of change. One such framework is latent growth modeling, perhaps the most important and influential statistical revolution to have recently occurred in the social and behavioral sciences. This paper presents a basic introduction to a latent growth modeling approach for analyzing repeated measures data. Included is the specification and interpretation of the growth factors, primary extensions such as the analysis of growth in multiple populations, and structural models including both precursors of growth, and subsequent outcomes hypothesized to be influenced by the growth functions. PMID- 20577583 TI - Middle and Late Latency ERP Components Discriminate between Adults, Typical Children, and Children with Sensory Processing Disorders. AB - This study examined whether combinations of middle latency sensory evoked potential components and late components, possibly indicative of cognitive processing, can discriminate between three sample groups; 18 adults (20-55 years), 25 typical children (5-10 years) and 28 children with sensory processing disorders (SPD) (5-12 years). Electroencephalography (EEG) recordings were made while participants heard random presentations of two auditory stimuli (1 and 3 kHz) each at two intensities (50 and 70 dB). Amplitude and latency measurements were obtained for the N1, P2, N2, and P3 components from the averaged event related potential (ERP) for each of the four auditory stimuli. Discriminant analyses revealed two functions, one which described the relationship of the components on SPD deficit continuum and one which described the relationship of these components on a developmental continuum. Together, these two functions correctly classified 90.5% of the participants as to their group membership. These results are discussed in relation to neurodevelopmental theories. PMID- 20577584 TI - Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature. AB - In this review, we summarize the subjective experiential phenomena and behavioral changes that are caused by electrical stimulation of the cerebral cortex or subcortical nuclei in awake and conscious human subjects. Our comprehensive review contains a detailed summary of the data obtained from electrical brain stimulation (EBS) in humans in the last 100 years. Findings from the EBS studies may provide an additional layer of information about the neural correlates of cognition and behavior in healthy human subjects, or the neuroanatomy of illusions and hallucinations in patients with psychosis and the brain symptomatogenic zones in patients with epilepsy. We discuss some fundamental concepts, issues, and remaining questions that have defined the field of EBS, and review the current state of knowledge about the mechanism of action of EBS suggesting that the modulation of activity within a localized, but distributed, neuroanatomical network might explain the perceptual and behavioral phenomena that are reported during focal electrical stimulation of the human brain. PMID- 20577585 TI - Typical and atypical development of functional human brain networks: insights from resting-state FMRI. AB - Over the past several decades, structural MRI studies have provided remarkable insights into human brain development by revealing the trajectory of gray and white matter maturation from childhood to adolescence and adulthood. In parallel, functional MRI studies have demonstrated changes in brain activation patterns accompanying cognitive development. Despite these advances, studying the maturation of functional brain networks underlying brain development continues to present unique scientific and methodological challenges. Resting-state fMRI (rsfMRI) has emerged as a novel method for investigating the development of large scale functional brain networks in infants and young children. We review existing rsfMRI developmental studies and discuss how this method has begun to make significant contributions to our understanding of maturing brain organization. In particular, rsfMRI has been used to complement studies in other modalities investigating the emergence of functional segregation and integration across short and long-range connections spanning the entire brain. We show that rsfMRI studies help to clarify and reveal important principles of functional brain development, including a shift from diffuse to focal activation patterns, and simultaneous pruning of local connectivity and strengthening of long-range connectivity with age. The insights gained from these studies also shed light on potentially disrupted functional networks underlying atypical cognitive development associated with neurodevelopmental disorders. We conclude by identifying critical gaps in the current literature, discussing methodological issues, and suggesting avenues for future research. PMID- 20577586 TI - High-Pass Filtering and Dynamic Gain Regulation Enhance Vertical Bursts Transmission along the Mossy Fiber Pathway of Cerebellum. AB - Signal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like) appearance of granular to molecular layer transmission. By using voltage-sensitive dye imaging in rat cerebellar slices (Mapelli et al., 2010), we found that mossy fiber bursts optimally excited the granular layer above approximately 50 Hz and the overlaying molecular layer above approximately 100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo. PMID- 20577587 TI - A cortical sparse distributed coding model linking mini- and macrocolumn-scale functionality. AB - No generic function for the minicolumn - i.e., one that would apply equally well to all cortical areas and species - has yet been proposed. I propose that the minicolumn does have a generic functionality, which only becomes clear when seen in the context of the function of the higher-level, subsuming unit, the macrocolumn. I propose that: (a) a macrocolumn's function is to store sparse distributed representations of its inputs and to be a recognizer of those inputs; and (b) the generic function of the minicolumn is to enforce macrocolumnar code sparseness. The minicolumn, defined here as a physically localized pool of approximately 20 L2/3 pyramidals, does this by acting as a winner-take-all (WTA) competitive module, implying that macrocolumnar codes consist of approximately 70 active L2/3 cells, assuming approximately 70 minicolumns per macrocolumn. I describe an algorithm for activating these codes during both learning and retrievals, which causes more similar inputs to map to more highly intersecting codes, a property which yields ultra-fast (immediate, first-shot) storage and retrieval. The algorithm achieves this by adding an amount of randomness (noise) into the code selection process, which is inversely proportional to an input's familiarity. I propose a possible mapping of the algorithm onto cortical circuitry, and adduce evidence for a neuromodulatory implementation of this familiarity-contingent noise mechanism. The model is distinguished from other recent columnar cortical circuit models in proposing a generic minicolumnar function in which a group of cells within the minicolumn, the L2/3 pyramidals, compete (WTA) to be part of the sparse distributed macrocolumnar code. PMID- 20577588 TI - Spatial Point Pattern Analysis of Neurons Using Ripley's K-Function in 3D. AB - The aim of this paper is to apply a non-parametric statistical tool, Ripley's K function, to analyze the 3-dimensional distribution of pyramidal neurons. Ripley's K-function is a widely used tool in spatial point pattern analysis. There are several approaches in 2D domains in which this function is executed and analyzed. Drawing consistent inferences on the underlying 3D point pattern distributions in various applications is of great importance as the acquisition of 3D biological data now poses lesser of a challenge due to technological progress. As of now, most of the applications of Ripley's K-function in 3D domains do not focus on the phenomenon of edge correction, which is discussed thoroughly in this paper. The main goal is to extend the theoretical and practical utilization of Ripley's K-function and corresponding tests based on bootstrap resampling from 2D to 3D domains. PMID- 20577589 TI - Reading as active sensing: a computational model of gaze planning in word recognition. AB - WE OFFER A COMPUTATIONAL MODEL OF GAZE PLANNING DURING READING THAT CONSISTS OF TWO MAIN COMPONENTS: a lexical representation network, acquiring lexical representations from input texts (a subset of the Italian CHILDES database), and a gaze planner, designed to recognize written words by mapping strings of characters onto lexical representations. The model implements an active sensing strategy that selects which characters of the input string are to be fixated, depending on the predictions dynamically made by the lexical representation network. We analyze the developmental trajectory of the system in performing the word recognition task as a function of both increasing lexical competence, and correspondingly increasing lexical prediction ability. We conclude by discussing how our approach can be scaled up in the context of an active sensing strategy applied to a robotic setting. PMID- 20577590 TI - The rewarding nature of social interactions. AB - The objective of this short review is to highlight rewarding aspects of social interactions for humans and discuss their neural basis. Thereby we report recent research findings to illustrate how social stimuli in general are processed in the reward system and highlight the role of Theory of Mind as one mediating process for experiencing social reward during social interactions. In conclusion we discuss clinical implications for psychiatry and psychotherapy. PMID- 20577591 TI - DPARSF: A MATLAB Toolbox for "Pipeline" Data Analysis of Resting-State fMRI. AB - Resting-state functional magnetic resonance imaging (fMRI) has attracted more and more attention because of its effectiveness, simplicity and non-invasiveness in exploration of the intrinsic functional architecture of the human brain. However, user-friendly toolbox for "pipeline" data analysis of resting-state fMRI is still lacking. Based on some functions in Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST), we have developed a MATLAB toolbox called Data Processing Assistant for Resting-State fMRI (DPARSF) for "pipeline" data analysis of resting-state fMRI. After the user arranges the Digital Imaging and Communications in Medicine (DICOM) files and click a few buttons to set parameters, DPARSF will then give all the preprocessed (slice timing, realign, normalize, smooth) data and results for functional connectivity, regional homogeneity, amplitude of low-frequency fluctuation (ALFF), and fractional ALFF. DPARSF can also create a report for excluding subjects with excessive head motion and generate a set of pictures for easily checking the effect of normalization. In addition, users can also use DPARSF to extract time courses from regions of interest. PMID- 20577592 TI - The neural substrate of prior information in perceptual decision making: a model based analysis. AB - PRIOR INFORMATION BIASES THE DECISION PROCESS: actions consistent with prior information are executed swiftly, whereas actions inconsistent with prior information are executed slowly. How is this bias implemented in the brain? To address this question we conducted an experiment in which people had to decide quickly whether a cloud of dots moved coherently to the left or to the right. Cues provided probabilistic information about the upcoming stimulus. Behavioral data were analyzed with the linear ballistic accumulator (LBA) model, confirming that people used the cue to bias their decisions. The functional magnetic resonance imaging (fMRI) data showed that presentation of the cue differentially activated orbitofrontal cortex, hippocampus, and the putamen. Directional cues selectively activated the contralateral putamen. The fMRI analysis yielded results only when the LBA bias parameter was included as a covariate, highlighting the practical benefits of formal modeling. Our results suggest that the human brain uses prior information by increasing cortico-striatal activation to selectively disinhibit preferred responses. PMID- 20577594 TI - Characterization and localization of side population cells in the lens. AB - PURPOSE: Side population (SP) cells were isolated and the possibility whether lens epithelial cells contain stem cells was investigated. METHODS: Mouse lens epithelial cells were stained by Hoechst 33342 and then sorted by fluorescence activated cell sorting (FACS). The expression of stem cell markers in sorted SP cells and the main population of epithelial cells were analyzed by quantitative real-time PCR. Localization of SP cells in the mouse lens was studied by fluorescence microscopy. RESULTS: The sorted cells contained SP cells, which were no longer separable by FACS following treatment with verapamil. The number of SP cells decreased with aging, but the adult mouse lens still contained SP cells. Phase contrast microscopy revealed that SP cells were smaller in size than non-SP cells. SP cells were localized near the equator region in lens epithelial cell layers. SP cells expressed higher levels of the stem cell markers ATP-binding cassette transporter G2 (ABCG2), p75 neurotrophin receptor (p75NTR), nestin (nes), B-cell lymphoma 2 (Bcl2), and cell surface antigen Sca-1 mRNA than the main population cells. These results suggest that SP cells contain a high proportion of stem cells. CONCLUSIONS: The SP cells in the lens contain stem cells, and these stem cells are localized around the germinative zone. PMID- 20577593 TI - Cysteinyl-glycine in the control of glutathione homeostasis in bovine lenses. AB - PURPOSE: To define a possible metabolic and/or signaling role for Cys-Gly in glutathione homeostasis in bovine eye lenses. METHODS: Bovine lenses were cultured up to 24 h in a medium containing 0.5 mM reduced glutathione (GSH) under different conditions. The intracellular and the extracellular contents of thiol compounds were evaluated using a free zone capillary electrophoresis method. RESULTS: Culture of lenses in the presence of GSH and the gamma-glutamyl transferase inhibitor serine-borate demonstrated a 1.5 fold increase in the level of extra-lenticular glutathione with respect to the initial value. Cys-Gly exogenously added impaired the extra-lenticular accumulation of glutathione. Both cysteine and gamma-Glu-Cys were ineffective in reducing extra-lenticular glutathione accumulation. In all conditions no differences in reduced and total intra-lenticular glutathione levels were observed. CONCLUSIONS: The impairment of Cys-Gly generation correlated with inhibition of gamma-glutamyl transferase by serine/borate, resulting in high extra-lenticular concentration of glutathione effluxed from the bovine lens. The possibility that Cys-Gly may intervene either in the replenishment processes for cysteine in the GSH biosynthetic step or in the function of the efflux GSH-transporters is considered. PMID- 20577595 TI - Identification of a novel mutation in the cornea specific keratin 12 gene causing Meesmann's corneal dystrophy in a German family. AB - PURPOSE: To report a novel missense mutation of the cornea specific keratin 12 (KRT12) gene in two generations of a German family diagnosed with Meesmann;s corneal dystrophy. METHODS: Ophthalmologic examination of the proband and sequencing of keratin 3 (KRT3) and KRT12 of the proband and three other family members were performed. Restriction enzyme analysis was used to confirm the detected mutation in affected individuals of the family. RESULTS: Slit-lamp biomicroscopy of the proband revealed multiple intraepithelial microcysts comparable to a Meesmann dystrophy phenotype. A novel heterozygous A-->G transversion at the first nucleotide position of codon 129 (ATG>GTG, M129V) in exon 1 of KRT12 was detected in the proband, her two affected sons but not in her unaffected husband or 50 control individuals. CONCLUSIONS: We have identified a novel missense mutation within the highly conserved helix-initiation motif of KRT12 causing Meesmann;s corneal dystrophy in a German family. PMID- 20577596 TI - Cotylenin A inhibits cell proliferation and induces apoptosis and PAX6 mRNA transcripts in retinoblastoma cell lines. AB - PURPOSE: Retinoblastoma, a childhood cancer of the retina, is caused by inactivation of the tumor suppressor gene retinoblastoma (RB). Cotylenin A (CN A), a novel fusicoccane-diterpene glycoside, accelerates the differentiation of several types of myeloid cell lines and is a candidate for a new type of anticancer therapeutic agent with this effect. However, whether CN-A has the same effect on retinoblastoma cells is unknown. We studied the response of two retinoblastoma cell lines, Y-79 and WERI-Rb-1, to CN-A. METHODS: We studied the response of two retinoblastoma cell lines to CN-A with respect to cell growth, apoptosis, morphology, mRNA, protein expression analysis of specific genes (N myc, cyclin-dependent kinase inhibitor 1A [P21], paired box gene 6 [PAX6], and rhodopsin [RHO]), and activity of three PAX6 promoters (P0, P1, and Palpha). RESULTS: CN-A inhibited cell proliferation and induced apoptosis via caspase activity in the two retinoblastoma cell lines. In addition, CN-A induced mRNA expression of P21, PAX6, and RHO and protein expression of P21. In Y-79 cells, PAX6 P1 promoter was activated by CN-A. In WERI-Rb-1 cells, PAX6 P0, P1, and Palpha promoter were activated by CN-A. CN-A decreased mRNA and protein expression of N-myc in two retinoblastoma cell lines. CONCLUSIONS: The responses of retinoblastoma cells to CN-A include inhibition of cell growth, induction of apoptosis, and the potential to change neuroblastoma characteristics of retinoblastoma cells. PMID- 20577597 TI - The 2M6 antigen is a Muller cell-specific intracellular membrane-associated protein of the sarcolemmal-membrane-associated protein family and is also TopAP. AB - PURPOSE: The differentiation marker 2M6 has been used to identify Muller cells within the developing chick retina for several years, although the molecular identity of 2M6 was not known. This study was aimed at determining the identity of the protein antigen recognized by the 2M6 monoclonal antibody. METHODS: Affinity chromatography and subsequent mass spectrometry were used to determine the molecular identity of the 2M6 antigen. Immunohistochemistry of monolayer preparations and paraffin-embedded sections of chick retina were performed to localize expression of the 2M6 antigen within cells of the chick retina. RESULTS: Mass spectrometry analyses revealed that the 2M6 antigen is identical (with 95% probability) to the protein known as Top(AP), which is a member of the sarcolemmal membrane-associated protein family of proteins. The 2M6 polypeptide is expressed by Muller glial cells as well as boundary cells within the chick retina. Expression localizes to intracellular membrane structures within those cells. CONCLUSIONS: Members of the sarcolemmal membrane-associated protein family of proteins have been implicated in structural and functional roles related to the cytoskeleton and Ca(+2) release from internal stores. It is thought that 2M6 plays a similar role in Muller cells of the vertebrate retina. PMID- 20577599 TI - Quality and Safety in Blood Supply in 2010. AB - The past two decades saw tremendous achievements in blood safety, which are due to the commitment of blood establishments and industry, progress in technology such as the improvement of serological and NAT screening tests, and stringent regulatory control. Milestones in the legislation were the inclusion of plasma derivatives in the pharmaceutical legislation of the European Community (EC) in the year 1989 and special laws for the blood sector in EC and in member states, such as the Transfusionsgesetz (Transfusion Law) in Germany. The legal frame has to be supplemented by scientific and technical guidance, which is provided on the European level by the European Directorate for the Quality of Medicines and Health Care and by the European Medicines Agency. In the member states, guidelines taking into account the national peculiarities can be elaborated, such as the German hemotherapy guidelines issued by the German Medical Association (Bundesarztekammer) in agreement with the Paul-Ehrlich-Institut. The regulatory control of screening tests, and the introduction of NAT testing lead to a remarkably high degree of safety concerning the most relevant viruses HIV, HBV and HCV. Issues needing further attention are bacterial contamination and transfusion-associated acute lung injury (TRALI). Measures aiming at minimizing risks have to be balanced against their impact on supply. In order to ensure the assured supply with safe blood products, sustained efforts and research are needed as well as a continuous dialogue among blood services, industry, physicians, patients and regulatory authorities. PMID- 20577598 TI - Laser injury promotes migration and integration of retinal progenitor cells into host retina. AB - PURPOSE: The migration and integration of grafted cells into diseased host tissue remains a critical challenge, particularly in the field of retinal progenitor cell (RPC) transplantation. It seems that natural physical barriers at the outer retina can impede the migration of grafted RPCs into the host retina. The purpose of this study was to investigate the integration and differentiation of murine RPCs transplanted into the subretinal space of mice with laser-induced damage to the outer retina. METHODS: RPCs were harvested from the neural retinas of postnatal day 1 enhanced green fluorescent protein (GFP) mice. Retinal photocoagulation was performed using a diode laser. Two microl containing approximately 6x10(5) expanded RPCs in suspension were injected into the subretinal space of the recipient animals following laser treatment. Cell morphometry was performed to assess the integration of donor cells. Immunohistochemistry and western blot were performed on recipient retinas. RESULTS: Three weeks after transplantation, 1,158+/-320 cells per eye had migrated into the recipient outer nuclear layer (ONL). Most of these cells resided in the ONL around the retinal laser lesion. A subpopulation of these cells developed morphological features reminiscent of mature photoreceptors, expressed photoreceptor specific proteins including synaptic protein, and appeared to form synaptic connections with bipolar neurons. Retinal photocoagulation resulted in a significantly increased expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and cluster differentiation 44 (CD44s), and a decreased expression of neurocan. CONCLUSIONS: Transplanted RPCs migrate and integrate into the laser-injured ONL where they differentiate into photoreceptors with morphological features reminiscent of mature photoreceptors, express synaptic protein, and appear to form synaptic connections with retinal bipolar neurons. Following retinal photocoagulation, the enhanced level of integration of grafted RPCs is partially associated with increased expression of MMP-2 and, to a lesser extent, MMP-9, together with decreased levels of inhibitory molecules. PMID- 20577600 TI - Quarantine Plasma: Quo vadis? AB - Upon the introduction of mandatory nucleic acid amplification technology (NAT) testing in Germany for HCV, quarantining of fresh frozen plasma (FFP) was reduced in 2002 from 6 to 4 months. In 2004 HIV-1 NAT and in 2005 anti-HBc testing were introduced to further reduce the residual transmission risks for transfusion relevant viruses. After testing more than 40 million donations by HCV NAT it became obvious that NAT testing has a very significant impact on viral blood safety by reducing the residual risk by a factor of 10. Only one documented HCV transmission occurred during more than 10 years of NAT testing in Germany, indicating that the remaining risk is marginal. Similar data were obtained for HIV-1. The question arises whether we could discontinue quarantining of FFP or further reduce the quarantining interval for retesting of the donor. This could facilitate logistics and reduce losses as quarantine FFP can be released earlier after donation and at regular donation intervals. Essential parameters for estimating the remaining infectious risks are the minimal infectious dose and replication kinetics of the viruses involved, the detection limits of the NAT tests applied, and the volume of plasma transfused. In essence it can be assumed that discontinuation of quarantining would only marginally increase the residual risk and that the reduction of the quarantine period to only 4 weeks would add an additional benefit to the viral safety of quarantine FFP. PMID- 20577601 TI - Epidemiological Data - an Important Part of the Hemovigilance System. AB - Epidemiological data are essential for monitoring trends and outbreaks of infectious diseases in the general population. The reporting system pursuant to the Infection Protection Act in Germany results in a very good quality of timely nationwide data on all reportable diseases including those relevant for the blood supply: HIV, hepatitis C, hepatitis B and syphilis. Notifications of acute hepatitis B and first-time diagnosed hepatitis C infections in the general population showed a declining trend in the past years, but the number of reports of HIV and syphilis infections increased until 2007 especially among men who have sex with men. New preventive strategies should also address changes in sexual behavior. The specific surveillance of blood donors is an important part of the hemovigilance system. The highly effective donor selection process results in a small number of confirmed infections among donors in Germany. The surveillance data enable us to identify specific trends that might challenge blood safety like the increase in HIV infections among repeat donors. Specific evaluations are performed when needed. These additional studies can be used to modify guidelines or recommendations and to (re)evaluate the need for or the effect of further testing. PMID- 20577602 TI - Role of pelvic lymphadenectomy in the treatment of bladder cancer: a mini review. AB - Although radical cystectomy with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive bladder cancer, the optimal extent of PLND and the minimum number of nodes that should be examined for pathology remain unclear. However, evidence is growing that extended PLND has additional diagnostic and therapeutic benefits relative to standard PLND. In particular, a more meticulous and extended PLND may improve the disease-free survival of node negative patients because it removes undetected micrometastases. Indeed, some patients with positive nodes can be cured by surgery alone, even those with gross adenopathy. Increasing lines of evidence also suggest that the extent of the primary bladder tumor, the number of lymph nodes that are removed, and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy. Therefore, extended PLND may not only provide improved prognostic information, it may also have a clinically significant therapeutic benefit for both lymph node-positive and node-negative patients undergoing radical cystectomy. Although the absolute limits of PLND remain to be determined, evidence supports the notion that a more extended PLND should include the common iliac vessels and presacral lymph nodes at cystectomy. Such PLND should only be performed in patients who are appropriate surgical candidates. Prospective, randomized trials are needed to properly establish the extent of PLND that is required to generate these benefits. PMID- 20577603 TI - Comparative Analysis between Immunochemotherapy and Target Therapy for Metastatic Renal Cell Carcinoma: Overview of Treatment-Related Adverse Events and the Dropout Rate in Korea. AB - PURPOSE: To comparatively analyze treatment-related adverse events and the treatment dropout rate between immunochemotherapy and target therapy in Korea. MATERIALS AND METHODS: Forty-nine subjects with metastatic renal cell carcinoma (21 target therapy recipients and 28 immunochemotherapy recipients) who underwent either 6-week cycles of sunitinib treatment (50 mg once daily for 4 weeks on and 2 weeks off) or 8-week cycles of immunochemotherapy (combination of interleukin [IL]-2, interferon [IFN]-alpha, and 5-fluorouracil [FU]) were enrolled. Treatment related toxicity was objectively graded and quantitative analysis was performed with a scoring system. Patient compliance was categorized into three classes (1: administration as scheduled, 2: dose modification required, 3: discontinuation required). RESULTS: Compared with those of the immunochemotherapy group, subjects of the sunitinib-treatment group had higher occurrence rates of mucositis stomatitis (43% vs. 10%), hand-foot syndrome (38% vs. 0%), diarrhea (33% vs. 14%), and hypertension (33% vs. 14%). According to the toxicity-grade-based scoring system, the total incidence and severity of toxicities were not significantly different between the two groups (p>0.05), whereas high-grade hematologic toxicities were more frequent in the immunochemotherapy group. The dropout rate of the immunochemotherapy group was significantly higher than that of the sunitinib group (administration as scheduled: 52% vs. 21%, p=0.026; discontinuation required: 19% vs. 50%, p=0.037). CONCLUSIONS: The results of this study are indicative of a comparable treatment-related toxicity profile of sunitinib and greater adherence to the treatment protocol in comparison with immunochemotherapy in patients with metastatic renal cell carcinoma (mRCC). PMID- 20577604 TI - Preoperative Clinical and Pathological Characteristics of pT0 Prostate Cancer in Radical Prostatectomy. AB - PURPOSE: To analyze the preoperative clinical and pathological characteristics of patients with pT0 prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 702 patients who underwent radical prostatectomy (RP) at our institution between January 2004 and July 2008 for clinically localized prostate cancer. If there was no evidence of residual tumor in the pathological specimen of the prostate, a patient was staged as pT0. Patients with pT0 disease were compared with a control group of patients who were operated on during the same period. RESULTS: Overall, 9 (1.3%) patients were staged as pT0 on the pathologic examination. Significant differences were observed between the pT0 group and the control patients in the biopsy Gleason score (p=0.004), the number of positive cores on biopsy (p=0.018), the tumor length of positive cores (p<0.001), and prostate volume (p=0.015). Cutoff values predictive of pT0 tumor status were defined as a biopsy Gleason score sum 30 cm(3). Whereas 8 of the 9 (88.9%) pT0 patients showed all of these characteristics, only 55 of the 693 (7.9%) control patients fulfilled the criteria. The combination suggested above afforded a sensitivity of 88.8% and a specificity of 92.1% for the prediction of pT0 status. CONCLUSIONS: The frequency of pT0 prostate cancer seen on RP was 1.3%. A combination of clinicopathological features, incorporating a biopsy Gleason score, the number of positive biopsy cores, tumor length on biopsy, and prostate volume, was useful to predict pT0 stage on RP. PMID- 20577605 TI - Predictors of PSA Screening Among Men Over 40 Years of Age Who Had Ever Heard about PSA. AB - PURPOSE: The purpose of this study was to investigate social and behavioral factors associated with prostate-specific antigen (PSA) screening in men in California, United States, who were over 40 years of age and had ever heard about PSA screening. MATERIALS AND METHODS: This survey was administered as a random digit-dialing telephone survey to produce reliable estimates of medium-sized counties. It surveyed 42,000 households and interviewed 58,407 people randomly. It considered socioeconomic status and health behavior as affecting PSA screening. Access to health care was measured as having regular health care access. The main outcome measure was self-report of ever having undergone PSA screening at least once in the respondent's lifetime. RESULTS: Of 8,864 respondents, 82.2% were White, 7.7% were Latin, 4.2% were African American, and 5.9% were Asian. The respondents' mean age was 60.13 years. Age was the significant factor for PSA screening. Respondents aged 50-59 years were 3.5 times as likely to have undergone PSA screening as were those aged 40-49 years (OR=3.49, p/=4 at baseline). We investigated the response rate, defined as clinical global impression improvement (CGI-I) /=7%) and the less weight gain (weight gain <7%) groups according to weight change between before and after long-term olanzapine treatment (440+/-288 days). All participants were genotyped for the GST-M1, GST-T1 and GST-P1 genes. Differences in allele frequencies between cohorts with different body weight changes were evaluated by a chi-square analysis and Fisher's exact test. The multifactor dimensionality reduction (MDR) approach was used to analyze gene-gene interactions. RESULTS: Mean body weight gain was 5.42 kg. There was no difference in the null genotype distribution of GST-M1 and -T1 between subjects with body weight gain >/=7% compared to subjects with body weight gain <7% (p>0.05). No significant difference in GST-P1 genotype and allele frequencies were observed between the groups (p>0.05). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to weight gain (p>0.05). CONCLUSION: These findings do not support a relationship between the genetic variants of three GST genes (GST-M1, -T1 and -P1) and weight gain in Korean schizophrenic patients receiving olanzapine treatment. PMID- 20577626 TI - Delirium associated with olanzapine therapy in an elderly male with bipolar affective disorder. AB - Atypical antipsychotic medications are commonly used to treat symptoms of delirium. Olanzapine has been successfully used in the treatment of delirium. However, there have been few case reports of delirium associated with olanzapine. We hereby report a case of delirium associated with olanzapine therapy. Possible risk factors and underlying pathogenesis is discussed. PMID- 20577627 TI - Bayesian inference for generalized linear models for spiking neurons. AB - Generalized Linear Models (GLMs) are commonly used statistical methods for modelling the relationship between neural population activity and presented stimuli. When the dimension of the parameter space is large, strong regularization has to be used in order to fit GLMs to datasets of realistic size without overfitting. By imposing properly chosen priors over parameters, Bayesian inference provides an effective and principled approach for achieving regularization. Here we show how the posterior distribution over model parameters of GLMs can be approximated by a Gaussian using the Expectation Propagation algorithm. In this way, we obtain an estimate of the posterior mean and posterior covariance, allowing us to calculate Bayesian confidence intervals that characterize the uncertainty about the optimal solution. From the posterior we also obtain a different point estimate, namely the posterior mean as opposed to the commonly used maximum a posteriori estimate. We systematically compare the different inference techniques on simulated as well as on multi-electrode recordings of retinal ganglion cells, and explore the effects of the chosen prior and the performance measure used. We find that good performance can be achieved by choosing an Laplace prior together with the posterior mean estimate. PMID- 20577628 TI - Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode. AB - A brush of 64 microwires was chronically implanted in the ventral premotor cortex of a macaque monkey. Contrary to common approaches, the wires were inserted from the white matter side. This approach, by avoiding mechanical pressure on the dura and pia mater during penetration, disturbed only minimally the cortical recording site. With this approach isolated potentials and multiunit activity were recorded for more than 7 years in about one-third of electrodes. The indirect insertion method also provided an excellent stability within each recording session, and in some cases even allowed recording from the same neurons for several years. Histological examination of the implanted brain region shows only a very marginal damage to the recording area. Advantages and problems related to long-term recording are discussed. PMID- 20577629 TI - Linking language with embodied and teleological representations of action for humanoid cognition. AB - The current research extends our framework for embodied language and action comprehension to include a teleological representation that allows goal-based reasoning for novel actions. The objective of this work is to implement and demonstrate the advantages of a hybrid, embodied-teleological approach to action language interaction, both from a theoretical perspective, and via results from human-robot interaction experiments with the iCub robot. We first demonstrate how a framework for embodied language comprehension allows the system to develop a baseline set of representations for processing goal-directed actions such as "take," "cover," and "give." Spoken language and visual perception are input modes for these representations, and the generation of spoken language is the output mode. Moving toward a teleological (goal-based reasoning) approach, a crucial component of the new system is the representation of the subcomponents of these actions, which includes relations between initial enabling states, and final resulting states for these actions. We demonstrate how grammatical categories including causal connectives (e.g., because, if-then) can allow spoken language to enrich the learned set of state-action-state (SAS) representations. We then examine how this enriched SAS inventory enhances the robot's ability to represent perceived actions in which the environment inhibits goal achievement. The paper addresses how language comes to reflect the structure of action, and how it can subsequently be used as an input and output vector for embodied and teleological aspects of action. PMID- 20577630 TI - Early history of glycine receptor biology in Mammalian spinal cord circuits. AB - In this review we provide an overview of key in vivo experiments undertaken in the cat spinal cord in the 1950s and 1960s, and point out their contributions to our present understanding of glycine receptor (GlyR) function. Importantly, some of these discoveries were made well before an inhibitory receptor, or its agonist, was identified. These contributions include the universal acceptance of a chemical mode of synaptic transmission; that GlyRs are chloride channels; are involved in reciprocal and recurrent spinal inhibition; are selectively blocked by strychnine; and can be distinguished from the GABA(A) receptor by their insensitivity to bicuculline. The early in vivo work on inhibitory mechanisms in spinal neurons also contributed to several enduring principles on synaptic function, such as the time associated with synaptic delay, the extension of Dale's hypothesis (regarding the chemical unity of nerve cells and their terminals) to neurons within the central nervous system, and the importance of inhibition for synaptic integration in motor and sensory circuits. We hope the work presented here will encourage those interested in GlyR biology and inhibitory mechanisms to seek out and read some of the "classic" articles that document the above discoveries. PMID- 20577631 TI - Direct visualization of the perforant pathway in the human brain with ex vivo diffusion tensor imaging. AB - Ex vivo magnetic resonance imaging yields high resolution images that reveal detailed cerebral anatomy and explicit cytoarchitecture in the cerebral cortex, subcortical structures, and white matter in the human brain. Our data illustrate neuroanatomical correlates of limbic circuitry with high resolution images at high field. In this report, we have studied ex vivo medial temporal lobe samples in high resolution structural MRI and high resolution diffusion MRI. Structural and diffusion MRIs were registered to each other and to histological sections stained for myelin for validation of the perforant pathway. We demonstrate probability maps and fiber tracking from diffusion tensor data that allows the direct visualization of the perforant pathway. Although it is not possible to validate the DTI data with invasive measures, results described here provide an additional line of evidence of the perforant pathway trajectory in the human brain and that the perforant pathway may cross the hippocampal sulcus. PMID- 20577632 TI - Directed coupling in local field potentials of macaque v4 during visual short term memory revealed by multivariate autoregressive models. AB - Processing and storage of sensory information is based on the interaction between different neural populations rather than the isolated activity of single neurons. In order to characterize the dynamic interaction and transient cooperation of sub circuits within a neural network, multivariate autoregressive (MVAR) models have proven to be an important analysis tool. In this study, we apply directed functional coupling based on MVAR models and describe the temporal and spatial changes of functional coupling between simultaneously recorded local field potentials in extrastriate area V4 during visual memory. Specifically, we compare the strength and directional relations of coupling based on generalized partial directed coherence (GPDC) measures while two rhesus monkeys perform a visual short-term memory task. In both monkeys we find increases in theta power during the memory period that are accompanied by changes in directed coupling. These interactions are most prominent in the low frequency range encompassing the theta band (3-12 Hz) and, more importantly, are asymmetric between pairs of recording sites. Furthermore, we find that the degree of interaction decreases as a function of distance between electrode positions, suggesting that these interactions are a predominantly local phenomenon. Taken together, our results show that directed coupling measures based on MVAR models are able to provide important insights into the spatial and temporal formation of local functionally coupled ensembles during visual memory in V4. Moreover, our findings suggest that visual memory is accompanied not only by a temporary increase of oscillatory activity in the theta band, but by a direction-dependent change in theta coupling, which ultimately represents a change in functional connectivity within the neural circuit. PMID- 20577633 TI - Large Deformation Diffeomorphic Metric Mapping Registration of Reconstructed 3D Histological Section Images and in vivo MR Images. AB - Our current understanding of neuroanatomical abnormalities in neuropsychiatric diseases is based largely on magnetic resonance imaging (MRI) and post mortem histological analyses of the brain. Further advances in elucidating altered brain structure in these human conditions might emerge from combining MRI and histological methods. We propose a multistage method for registering 3D volumes reconstructed from histological sections to corresponding in vivo MRI volumes from the same subjects: (1) manual segmentation of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) compartments in histological sections, (2) alignment of consecutive histological sections using 2D rigid transformation to construct a 3D histological image volume from the aligned sections, (3) registration of reconstructed 3D histological volumes to the corresponding 3D MRI volumes using 3D affine transformation, (4) intensity normalization of images via histogram matching, and (5) registration of the volumes via intensity based large deformation diffeomorphic metric (LDDMM) image matching algorithm. Here we demonstrate the utility of our method in the transfer of cytoarchitectonic information from histological sections to identify regions of interest in MRI scans of nine adult macaque brains for morphometric analyses. LDDMM improved the accuracy of the registration via decreased distances between GM/CSF surfaces after LDDMM (0.39 +/- 0.13 mm) compared to distances after affine registration (0.76 +/- 0.41 mm). Similarly, WM/GM distances decreased to 0.28 +/- 0.16 mm after LDDMM compared to 0.54 +/- 0.39 mm after affine registration. The multistage registration method may find broad application for mapping histologically based information, for example, receptor distributions, gene expression, onto MRI volumes. PMID- 20577634 TI - Biocompatibility of intracortical microelectrodes: current status and future prospects. AB - Rehabilitation of sensory and/or motor functions in patients with neurological diseases is more and more dealing with artificial electrical stimulation and recording from populations of neurons using biocompatible chronic implants. As more and more patients have benefited from these approaches, the interest in neural interfaces has grown significantly. However an important problem reported with all available microelectrodes to date is long-term viability and biocompatibility. Therefore it is essential to understand the signals that lead to neuroglial activation and create a targeted intervention to control the response, reduce the adverse nature of the reactions and maintain an ideal environment for the brain-electrode interface. We discuss some of the exciting opportunities and challenges that lie in this intersection of neuroscience research, bioengineering, neurology and biomaterials. PMID- 20577635 TI - 3-Dimensional Scene Perception during Active Electrolocation in a Weakly Electric Pulse Fish. AB - Weakly electric fish use active electrolocation for object detection and orientation in their environment even in complete darkness. The African mormyrid Gnathonemus petersii can detect object parameters, such as material, size, shape, and distance. Here, we tested whether individuals of this species can learn to identify 3-dimensional objects independently of the training conditions and independently of the object's position in space (rotation-invariance; size constancy). Individual G. petersii were trained in a two-alternative forced choice procedure to electrically discriminate between a 3-dimensional object (S+) and several alternative objects (S-). Fish were then tested whether they could identify the S+ among novel objects and whether single components of S+ were sufficient for recognition. Size-constancy was investigated by presenting the S+ together with a larger version at different distances. Rotation-invariance was tested by rotating S+ and/or S- in 3D. Our results show that electrolocating G. petersii could (1) recognize an object independently of the S- used during training. When only single components of a complex S+ were offered, recognition of S+ was more or less affected depending on which part was used. (2) Object-size was detected independently of object distance, i.e. fish showed size-constancy. (3) The majority of the fishes tested recognized their S+ even if it was rotated in space, i.e. these fishes showed rotation-invariance. (4) Object recognition was restricted to the near field around the fish and failed when objects were moved more than about 4 cm away from the animals. Our results indicate that even in complete darkness our G. petersii were capable of complex 3-dimensional scene perception using active electrolocation. PMID- 20577637 TI - Optogenetically Induced Olfactory Stimulation in Drosophila Larvae Reveals the Neuronal Basis of Odor-Aversion behavior. AB - Olfactory stimulation induces an odor-guided crawling behavior of Drosophila melanogaster larvae characterized by either an attractive or a repellent reaction. In order to understand the underlying processes leading to these orientations we stimulated single olfactory receptor neurons (ORNs) through photo activation within an intact neuronal network. Using the Gal4-UAS system two light inducible proteins, the light-sensitive cation channel channelrhodopsin-2 (ChR-2) or the light-sensitive adenylyl cyclase (Pacalpha) were expressed in all or in individual ORNs of the larval olfactory system. Blue light stimulation caused an activation of these neurons, ultimately producing the illusion of an odor stimulus. Larvae were tested in a phototaxis assay for their orientation toward or away from the light source. Here we show that activation of Pacalpha expressing ORNs bearing the receptors Or33b or Or45a in blind norpA mutant larvae induces a repellent behavior away from the light. Conversely, photo-activation of the majority of ORNs induces attraction towards the light. Interestingly, in wild type larvae two ligands of Or33b and Or45a, octyl acetate and propionic ethylester, respectively, have been found to cause an escape reaction. Therefore, we combined light and odor stimulation to analyze the function of Or33b and Or45a expressing ORNs. We show that the larval olfactory system contains a designated neuronal pathway for repellent odorants and that activation of a specific class of ORNs already determines olfactory avoidance behavior. PMID- 20577636 TI - Arc/Arg3.1 mRNA global expression patterns elicited by memory recall in cerebral cortex differ for remote versus recent spatial memories. AB - The neocortex plays a critical role in the gradual formation and storage of remote declarative memories. Because the circuitry mechanisms of systems-level consolidation are not well understood, the precise cortical sites for memory storage and the nature of enduring memory correlates (mnemonic plasticity) are largely unknown. Detailed maps of neuronal activity underlying recent and remote memory recall highlight brain regions that participate in systems consolidation and constitute putative storage sites, and thus may facilitate detection of mnemonic plasticity. To localize cortical regions involved in the recall of a spatial memory task, we trained rats in a water-maze and then mapped mRNA expression patterns of a neuronal activity marker Arc/Arg3.1 (Arc) upon recall of recent (24 h after training) or remote (1 month after training) memories and compared them with swimming and naive controls. Arc gene expression was significantly more robust 24 h after training compared to 1 month after training. Arc expression diminished in the parietal, cingulate and visual areas, but select segments in the prefrontal, retrosplenial, somatosensory and motor cortical showed similar robust increases in the Arc expression. When Arc expression was compared across select segments of sensory, motor and associative regions within recent and remote memory groups, the overall magnitude and cortical laminar patterns of task-specific Arc expression were similar (stereotypical). Arc mRNA fractions expressed in the upper cortical layers (2/3, 4) increased after both recent and remote recall, while layer 6 fractions decreased only after the recent recall. The data suggest that robust recall of remote memory requires an overall smaller increase in neuronal activity within fewer cortical segments. This activity trend highlights the difficulty in detecting the storage sites and plasticity underlying remote memory. Application of the Arc maps may ameliorate this difficulty. PMID- 20577638 TI - Spatial Relationship between Flavoprotein Fluorescence and the Hemodynamic Response in the Primary Visual Cortex of Alert Macaque Monkeys. AB - Flavoprotein fluorescence imaging (FFI) is a novel intrinsic optical signal that is steadily gaining ground as a valuable imaging tool in neuroscience research due to its closer relationship with local metabolism relative to the more commonly used hemodynamic signals. We have developed a technique for FFI imaging in the primary visual cortex (V1) of alert monkeys. Due to the nature of neurovascular coupling, hemodynamic signals are known to spread beyond the locus of metabolic activity. To determine whether FFI signals could provide a more focal measure of cortical activity in alert animals, we compared FFI and hemodynamic point spreads (i.e. responses to a minimal visual stimulus) and functional mapping signals over V1 in macaques performing simple fixation tasks. FFI responses were biphasic, with an early and focal fluorescence increase followed by a delayed and spatially broader fluorescence decrease. As expected, the early fluorescence increase, indicating increased local oxidative metabolism, was somewhat narrower than the simultaneously observed hemodynamic response. However, the later FFI decrease was broader than the hemodynamic response and started prior to the cessation of visual stimulation suggesting different mechanisms underlying the two phases of the fluorescence signal. FFI mapping signals were free of vascular artifacts and comparable in amplitude to hemodynamic mapping signals. These results indicate that the FFI response may be a more local and direct indicator of cortical metabolism than the hemodynamic response in alert animals. PMID- 20577639 TI - Towards single-cell real-time imaging of energy metabolism in the brain. PMID- 20577641 TI - Microglial activation and neuroinflammation in Alzheimer's disease: a critical examination of recent history. AB - The neurofibrillary degeneration that occurs in Alzheimer's disease (AD) is thought to be the result of a chronic and damaging neuroinflammatory response mediated by neurotoxic substances produced by activated microglial cells. This neuroinflammation hypothesis of AD pathogenesis has led to numerous clinical trials with anti-inflammatory drugs, none of which have shown clear benefits for slowing or preventing disease onset and progression. In this paper, I make the point that AD is not an inflammatory condition, and reconstruct the sequence of events during the 1980s and 1990s that I believe led to the development of this faulty theory. PMID- 20577640 TI - Cross-talk between mitochondria and proteasome in Parkinson's disease pathogenesis. AB - Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder, characterized by the selective loss of nigrostriatal dopaminergic neurons, and the presence of intracellular insoluble proteinaceous inclusions, known as Lewy Bodies. Although PD etiopathogenesis remains elusive, the leading hypothesis for the death of specific groups of neurons establishes that mitochondrial dysfunction, alterations in the ubiquitin-proteasomal system (UPS), and oxidative stress are major events that act synergistically causing this devastating disease. In this review we will focus on mitochondrial impairment and its implications on proteasomal function and alpha-synuclein aggregation. We will address the role of mitochondria and proteasome cross-talk in the neuronal loss that leads to PD and discuss how this knowledge might further improve patient therapy. PMID- 20577642 TI - Cost analysis of Topical Negative Pressure (TNP) Therapy for traumatic acquired wounds. AB - Extended traumatic wounds require extended reconstructive operations and are accompanied by long hospitalizations and risks of infection, thrombosis and flap loss. In particular, the frequently used Topical Negative Pressure (TNP) Therapy is regarded as cost-intensive. The costs of TNP in the context of traumatic wounds is analyzed using the method of health economic evaluation. All patients (n=67: 45 male, 22 female; average age 54 y) with traumatically acquired wounds being treated with TNP at the university hospital of Goettingen in the period 01/01/2005-31/12/2007 comprise the basis for this analysis. The concept of activity-based costing based on clinical pathways according to InEK (National Institute for the Hospital Remuneration System) systematic calculations was chosen for cost accounting. In addition, a special module system adaptable for individual courses of disease was developed. The treated wounds were located on a lower extremity in 83.7% of cases (n=56) and on an upper extremity in 16.3% of cases (n=11). The average time of hospitalization of the patients was 54 days. Twenty-five patients (37.31%) exceeded the "maximum length of stay" of their associated DRG (Diagnosis Related Groups). The total PCCL (patient clinical complexity level = patient severity score) of 2.99 reflects the seriousness of disease. For the treatment of the 67 patients, total costs were $1,729,922.32 (1,249,176.91 euro). The cost calculation showed a financial deficit of $ 210,932.50 (-152,314.36 euro). Within the entire treatment costs of $218,848.07 (158,030.19 euro), 12.65% per case were created by TNP with material costs of $102,528.74 (74,036 euro), representing 5.92% of entire costs. The cost of TNP per patient averaged $3,266.39 (2,358.66 euro). The main portion of the costs was not - as is often expected - due to high material costs of TNP but instead to long-term treatments. Because of their complexity, the cases are insufficiently represented in the lump-sum calculation of the InEK. A differentiated integration of complex TNP-treatment in the DRG system (e.g., as an expanded DRG I98Z) would be a step towards cost recovery. In addition, the refunding of outpatient TNP treatment would lead to enhanced quality of life for the patients and to a reduction of hospital costs and length of stay. PMID- 20577643 TI - S3 guidelines for intensive care in cardiac surgery patients: hemodynamic monitoring and cardiocirculary system. AB - Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft fur Thorax-, Herz- und Gefasschirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft fur Anasthesiologie und lntensivmedizin, DGAI) made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF). PMID- 20577644 TI - Increased mortality in hypernatremic burned patients. AB - INTRODUCTION: In-hospital hypernatremia develops usually iatrogenically from inadequate or inappropriate fluid prescription. In severely burned patient an extensive initial fluid resuscitation is necessary for burn shock survival. After recovering of cellular integrity the circulating volume has to be normalized. Hereby extensive water and electrolyte shifts can provoke hypernatremia. PURPOSE: Is a hypernatremic state associated with increased mortality? METHOD: Retrospective study for the incidence of hypernatremia and survival in 40 patients with a totally burned surface area (TBSA) >10%. Age, sex, TBSA, ABSI Score and fluid resuscitation within the first 24 hours were analyzed. Patients were separated in two groups without (Group A) or with (Group B) hypernatremia. RESULTS: Hypernatremia occurred on day 5+/-1.4. No significant difference for age, sex, TBSA, ABSI-Score and fluid resuscitation within the first 24 hours were calculated. In Group A all patients survived, while 3 of the hypernatremic patient in Group B died during ICU-stay (Odds-ratio = 1.25; 95% CI 0.971-1.61; p=0.046). CONCLUSION: Burned patients with an in-hospital acquired hypernatremia have an increased mortality risk. In case of a hypernatremic state early intervention is obligatory. There is a need of a fluid removal strategy in severely burned patient to avoid water imbalance. PMID- 20577645 TI - Early postoperative alterations of ventilation parameters after tracheostomy in major burn injuries. AB - PURPOSE: In patients with major burn injuries mechanical ventilation is often required for longer periods. Tracheostomy (TS) plays an integral role in airway management. We investigated the effect of TS on ventilation parameters within 8 hours after TS. MATERIALS: A retrospective analysis of severely burned patients admitted to the burn unit of a German University Hospital was performed. Ventilation parameters 8 hours before and after TS were registered. RESULTS: A retrospective analysis of 20 patients which received surgical TS was performed. Mean age was 52+/-19 years. Mean abbreviated burned severity index (ABSI) was 8.3+/-2.2. A mechanical ventilation was required for 14.3+/-4.8 days. TS was performed on day 7+/-4. Inspiratory oxygen concentration (FiO(2)) (p<0.001), peak inspiratory pressure (p<0.001), positive end-expiratory pressure (p=0.003) and pulmonary resistance (p<0.001) were reduced significantly after TS. The arterial partial pressure of oxygen/FiO(2)-ratio increased significantly after TS (p<0.001). CONCLUSIONS: We demonstrate that TS reduces invasiveness of ventilation in severely burned patients and by this can optimize lung protective ventilation strategy. PMID- 20577647 TI - Building an international nursing outcomes research agenda. AB - A program of research begins with a good idea that materializes into a series of studies that carry the same theme. Each study builds upon the last, expanding on the findings to generate new questions, thus building the evidence base. The Center for Health Outcomes and Policy Research has built a 20-year program of research that has made great strides in establishing the evidence base that professional nurse practice models of care positively influence patient outcomes. This paper traces the evolution of the Center's program of research from a one state focus to an international enterprise. PMID- 20577646 TI - Respected Sir(2): magic target for diabetes. AB - The endless quest for the 'fountain of youth' has led to the discovery of a family of molecules known as sirtuins in humans, or silent mating type information regulator 2 (Sir2) in yeast, which are associated with longevity in yeast, nematodes, drosophila and rodents. Although sirtuins have yet to be proven to delay aging and promote longevity in humans, they promise 'healthy aging', an ideal of modern society. This review emphasizes the role of various sirtuins in maintaining glucose homeostasis, the therapeutic potential of sirtuin modulators in the prevention and treatment of diabetes, and the emerging associations of SIRT genetic polymorphisms with human longevity. PMID- 20577648 TI - Ultrasonography of the Anterior Segment. PMID- 20577650 TI - PIP2: a new key player in Alzheimer's disease. AB - Amyloid-beta peptide (Abeta) oligomers are likely to underlie the earliest amnesic changes in Alzheimer's disease through impairment of synaptic function. A recent work from the laboratories of Tae-Wan Kim and Gilbert Di Paolo and colleagues implicates the phosphoinositide signaling pathway in synaptic changes due to elevation of Abeta oligomers. Given that phosphatidylinositol 4,5 bisphosphate (PIP2) is central to many essential processes in neurons including neuronal and synaptic function, reduction in the levels of PIP2 in response to oligomeric Abeta could explain many of the phenotypes that have been observed with oligomeric Abeta. The data open up a new target for protecting neurons from Abeta-induced synaptic impairment. PMID- 20577649 TI - Palladium-Catalyzed Carboetherification and Carboamination Reactions of gamma Hydroxy- and gamma-Aminoalkenes for the Synthesis of Tetrahydrofurans and Pyrrolidines. AB - Substituted tetrahydrofuran and pyrrolidine moieties are displayed in a wide range of interesting biologically active molecules. The Pd-catalyzed carboetherification or carboamination of gamma-hydroxy- and gamma-aminoalkenes is a powerful tool for the construction of these heterocycles, as it is convergent and can allow access to a variety of analogs from a single gamma-hydroxy- or gamma-aminoalkene starting material. This microreview describes the current state of this field. PMID- 20577651 TI - Novel insights into non-image forming visual processing in the retina. AB - A small subset of retinal ganglion cells projecting to the suprachiasmatic nucleus and other brain areas, is implicated in non-image forming visual responses to environmental light such as the pupillary light reflex, seasonal adaptations in physiology, photic inhibition of nocturnal melatonin release, and modulation of sleep, alertness and activity. These cells are intrinsically photosensitive (ipRGCs) and express an opsin-like photopigment called melanopsin. Two recent studies utilizing selective genetic ablation of ipRGCs demonstrate the key role of these inner retinal cells in conveying luminance signals to the brain for non-image forming visual processing. These findings advance our understanding of functional organization of a novel photosensory system in the mammalian retina, demonstrating well-defined roles for ipRGCs in circadian timing and other homeostatic functions related to ambient illumination. PMID- 20577652 TI - Evaluating the Proportion of Treatment Effect Explained by a Continuous Surrogate Marker in Logistic or Probit Regression Models. AB - Using surrogate endpoints in clinical trials is desirable for drug development because the trials can be shortened and therefore more cost-effective. Validating a surrogate for the clinical endpoint is critical in this context. One of the key steps in statistical validation of a surrogate for a single trial is to estimate the proportion of treatment effect explained (PTE or PE) by a surrogate. Often the measure for PTE is estimated from the difference in coefficients of treatment from two models with or without adjusting for the surrogate for clinical endpoint. Inherent problems with the method are: the two models may not be valid simultaneously; and the estimate can often lie outside the interval [0, 1]. In this article, we provide alternative measures for evaluating the proportion of treatment effect explained by a surrogate in logistic or probit regression models. Our measures can be estimated easily with any statistical programs capable of binary linear regression modeling, and the interpretation of the measures can be illustrated using Ordinal Dominance (OD) curves. The concept can be visually understood by any practical user. Simulation shows our alternative measures yield more accurate estimates which are less biased, less variable, and with narrower confidence intervals. A clinical trial example is provided. PMID- 20577653 TI - Candidate genes for chromosomes 6 and 10 quantitative trait loci for age-related retinal degeneration in mice. AB - PURPOSE: In a previous study, several quantitative trait loci (QTL) that influence age-related degeneration (ageRD) were identified in a cross between the albino strains B6(Cg)-Tyr(c-2J)/J (B6a) and BALB/cByJ (C). The Chromosome (Chr) 6 and Chr 10 QTL were the strongest and most highly significant loci and both involved B6a protective alleles. The QTL were responsible for 21% and 9% of the variance in phenotypes, respectively. We focused on these two QTL to identify candidate genes. METHODS: DNA microarrays were used for the two mouse strains at four and eight months of age to identify genes that are differentially regulated and map to either QTL. Gene Ontology (GO) analysis of the differentially expressed genes was performed to identify possible processes and pathways associated with ageRD. To identify additional candidates, database analyses (Positional Medline or PosMed) were used. Based on differential expression, PosMed, and the presence of reported polymorphisms, five genes per QTL were selected for further study by sequencing analysis and qRT-PCR. Tumor necrosis factor, alpha- induced protein 3 (Tnfaip3; on a C57BL/6J (B6) background) was phenotypically tested. Single nucleotide polymorphisms (SNPs) flanking this gene were correlated with outer nuclear layer thickness (ONL), and eight-month-old Tnfaip3(+/-) mice were tested for ageRD. RESULTS: Polymorphisms were found in the coding regions of eight genes. Changes in gene expression were identified by qRT PCR for Hexokinase 2 (Hk2) and Docking protein 1 (Dok1) at four months and for Dok1 and Tnfaip3 at eight months. Tnfaip3 was selected for phenotypic testing due to differential expression and the presence of two nonsynonymous mutations. However, when ONL thickness was compared in eight-month-old congenic Tnfaip3(+/-) and Tnfaip3(+/+) mice, no differences were found, suggesting that Tnfaip3 is not the quantitative trait gene (QTG) for the Chr 10 QTL. The GO analysis revealed that GO terms associated with stress and cell remodeling are overrepresented in the ageRD-sensitive C strain compared with the B6a strain with age (eight months). In the ageRD-resistant B6a strain, compared with the C strain, GO terms associated with antioxidant response and the regulation of blood vessel size are overrepresented with age. CONCLUSIONS: The analyses of differentially expressed genes and the PosMed database yielded candidate genes for the Chr 6 and Chr 10 QTL. HtrA serine peptidase 2 (Htra2), Dok1, and Tnfaip3 were deemed most promising because of their known roles in apoptosis and our finding of nonsynonymous substitutions between B6a and C strains. While Tnfaip3 was excluded as the QTG for the Chr 10 QTL, Dok1 and Htra2 remain good candidates for the Chr 6 QTL. Finally, the GO term analysis further supports the general hypothesis that oxidative stress is involved in ageRD. PMID- 20577654 TI - XRCC1, but not APE1 and hOGG1 gene polymorphisms is a risk factor for pterygium. AB - PURPOSE: Epidemiological evidence suggests that UV irradiation plays an important role in pterygium pathogenesis. UV irradiation can produce a wide range of DNA damage. The base excision repair (BER) pathway is considered the most important pathway involved in the repair of radiation-induced DNA damage. Based on previous studies, single-nucleotide polymorphisms (SNPs) in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP-endonuclease-1 (APE1) genes in the BER pathway have been found to affect the individual sensitivity to radiation exposure and induction of DNA damage. Therefore, we hypothesize that the genetic polymorphisms of these repair genes increase the risk of pterygium. METHODS: XRCC1, APE1, and hOGG1 polymorphisms were studied using fluorescence labeled Taq Man probes on 83 pterygial specimens and 206 normal controls. RESULTS: There was a significant difference between the case and control groups in the XRCC1 genotype (p=0.038) but not in hOGG1 (p=0.383) and APE1 (p=0.898). The odds ratio of the XRCC1 A/G polymorphism was 2.592 (95% CI=1.225-5.484, p=0.013) and the G/G polymorphism was 1.212 (95% CI=0.914-1.607), compared to the A/A wild-type genotype. Moreover, individuals who carried at least one C-allele (A/G and G/G) had a 1.710 fold increased risk of developing pterygium compared to those who carried the A/A wild type genotype (OR=1.710; 95% CI: 1.015-2.882, p=0.044). The hOGG1 and APE1 polymorphisms did not have an increased odds ratio compared with the wild type. CONCLUSIONS: XRCC1 (Arg399 Glu) is correlated with pterygium and might become a potential marker for the prediction of pterygium susceptibility. PMID- 20577656 TI - A missense mutation in CRYBA4 associated with congenital cataract and microcornea. AB - PURPOSE: To identify mutations in a Chinese family with congenital cataract and microcornea. METHODS: Detailed family history and clinical data were recorded. Genomic DNA was extracted from leukocytes of venous blood of the patients and noncarriers in this family along with 100 normal individuals. All six exons of crystallin, beta A4 gene (CRYBA4) were amplified by PCR methods and direct sequencing. RESULTS: We identified a c.225G>T sequence change that led to an amino acid substitution G64W in the CRYBA4-induced protein in two patients of this family; this nucleotide substitution was not detected in the other individuals. CONCLUSIONS: A novel missense mutation in CRYBA4 was identified in our study. It expands the mutation spectrum of CRYBA4 and provides useful information to the study of molecular pathogenesis of cataract and microcornea. PMID- 20577655 TI - Sodium 4-phenylbutyrate ameliorates the effects of cataract-causing mutant gammaD crystallin in cultured cells. AB - PURPOSE: gammaD-Crystallin (CRYGD) is a major structural lens crystallin and its mutations result in congenital cataract formation. In this study, we attempted to correct the altered protein features of G165fsX8 CRYGD protein with small chemical molecules. METHODS: Recombinant FLAG-tagged mutants (R15C, R15S, P24T, R61C, and G165fsX8) of CRYGD were expressed in COS-7 cells and treated with small chemical molecules with reported protein chaperoning properties (sodium 4 phenylbutyrate [4-PBA], trimethylamine N-oxide [TMAO], and glycerol and DMSO [DMSO]). Protein solubility in 0.5% Triton X-100 and subcellular distribution was examined by western blotting and immunofluorescence, respectively. Apoptosis was assayed as the percentage of fragmented nuclei in transfected cells. Expression of heat-shock proteins (Hsp70 and Hsp90) was examined by reverse transcription polymerase chain reaction analysis. RESULTS: Unlike WT and most mutants (R15C, R15S, P24T, and R61C) of CRYGD, G165fsX8 CRYGD was significantly insoluble in 0.5% Triton X-100. This insolubility was alleviated by dose-dependent 4-PBA treatment. The treatment relieved the mislocalization of G165fsX8 CRYGD from the nuclear envelope. Also, 4-PBA treatment reduced cell apoptosis and caused an upregulation of Hsp70. CONCLUSIONS: 4-PBA treatment reduced the defective phenotype of mutant G165fsX8 CRYGD and rescued the affected cells from apoptosis. This could be a potential treatment for lens structural protein and prevent lens opacity in cataract formation. PMID- 20577657 TI - A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain. AB - BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID- 20577658 TI - What do the parents of children who have chronic pain expect from their first visit to a pediatric chronic pain clinic? AB - BACKGROUND: Chronic pain in childhood is increasingly recognized as a significant clinical problem. Best-practice management of pediatric chronic pain in a multidisciplinary pain clinic involves a variety of treatment modalities. It is important that parents of children treated in these settings understand the different treatment options available for their children. By involving parents more effectively, care providers may more efficiently address unmet treatment needs and improve tailoring of treatment programs aimed at increasing function, reducing pain-related disability and improving quality of life. OBJECTIVES: To explore the expectations held by parents for their first visit to a pediatric multidisciplinary pain clinic. METHODS: Fourteen parents completed a paper-based survey exploring their expectations immediately before their first visit to a multidisciplinary pediatric pain clinic in a tertiary care children's hospital. RESULTS: Responses from parents suggest a clear desire for information about the causes of their child's pain, treatment options available at the pain clinic, effective strategies to enhance children's ability to cope with pain, and the effects of pain on both body and mood. Most parents rated the various treatment options as important for their child. All parents indicated it was very important to have the pain team 'be there' for them. CONCLUSIONS: These findings indicate that parents want more information about chronic pain and treatment options. Pediatric chronic pain clinics have the ability to assist children with chronic pain and their families considerably by providing information about chronic pain and the various treatment options available to them. PMID- 20577659 TI - Postoperative self-report of pain in children: interscale agreement, response to analgesic, and preference for a faces scale and a visual analogue scale. AB - OBJECTIVE: To augment available validation data for the Faces Pain Scale - Revised (FPS-R) and to assess interscale agreement and preference in comparison with the Coloured Analogue Scale (CAS) in pediatric acute pain. METHOD: The present prospective, multicentre study included 131 inpatients five to 15 years of age (mean age 8.8 years; 56% male) seen in postoperative recovery. They provided CAS and FPS-R pain scores before and after administration of analgesic medication. Nurses and physicians used the same tools as observational scales. Children and health care providers indicated which scale they preferred. RESULTS: FPS-R scores for the intensity of postoperative pain correlated highly with the corresponding CAS scores in all age groups (0.66 eta(1) allyl isomerisation. Both amide and phenolic protons in 5a-5d were smoothly deprotonated, with base, to give the kappa(4) PNN'O-tetradentate complexes 11a/11b and 11d/11e containing the dianionic ligands 3a(2-)/3d(2-) respectively. The Ni(II) complexes 11c and 11f were synthesised directly from NiCl2 x 6 H2O, 3a x HH (or 3d x HH) and tBuOK in CH3OH. All new compounds were characterised by multinuclear NMR, FT-IR, mass spectrometry and microanalysis. Single crystal X-ray studies have been undertaken on the compounds 3a x HH, 3c x HH, 4a, 7c, 8a, 8b, 8d and 11a-11d. PMID- 20577685 TI - 3',5'-Cyclic diguanylic acid: a small nucleotide that makes big impacts. AB - 3',5'-Cyclic diguanylic acid (c-di-GMP) is a naturally occurring small cyclic dinucleotide found in bacteria. There has been a recent surge of interest in the two-component signalling networks involving this molecule. This tutorial review introduces the biosynthesis of c-di-GMP, particularly the conserved domain features involved in its enzymatic synthesis and degradation, cellular functions and phenotypes regulated by c-di-GMP through c-di-GMP-binding proteins. The chemical synthesis and structural studies of c-di-GMP are also summarized. Two potential applications of c-di-GMP, i.e. bacterial biofilm formation and immunostimulation, are surveyed. Recent observations on c-di-GMP-binding riboswitches are also introduced. PMID- 20577686 TI - Self-promotion mechanism for CO electrooxidation on gold. AB - CO electrooxidation on Au(111), Au(100) and Au(110) electrodes in 0.1 M HClO(4) and 0.1 M NaOH solutions has been studied by means of voltammetric measurements with hanging meniscus rotating bead-type electrodes. It is found that the reaction order in CO concentration is close to unity at potentials close to the onset of CO oxidation, and then it becomes higher than unity at higher potentials for all studied surfaces except for Au(111) in 0.1 M HClO(4). This behavior indicates that CO oxidation on gold takes place through a self-promotion mechanism, in which the presence of CO on the gold surface enhances the adsorption of its own oxidant. Specifically, this mechanism offers a plausible explanation for the higher catalytic activity in alkaline solutions, since CO adsorption is stronger under these conditions, and thus it can lead to a higher enhancement of the adsorption of the oxidant species. PMID- 20577687 TI - Measurement of hetero-nuclear distances using a symmetry-based pulse sequence in solid-state NMR. AB - A Symmetry-based Resonance-Echo DOuble-Resonance (S-REDOR) method is proposed for measuring hetero-nuclear dipolar couplings between two different spin-1/2 nuclei, under fast magic-angle spinning. The hetero-nuclear dipolar couplings are restored by employing the SR4 sequence, which requires the rf-field strength to be only twice the spinning frequency. The S-REDOR experiment is extended to S RESPDOR (Symmetry-based Resonance-Echo Saturation-Pulse DOuble-Resonance) for determining dipolar coupling between a spin-1/2 nucleus (e.g.(13)C) and (14)N. It is demonstrated that S-REDOR and S-RESPDOR methods suppress efficiently the homo nuclear dipolar interaction of the irradiated nucleus and benefit from high robustness to the rf-field inhomogeneity, chemical shielding and dipolar truncation. Therefore, these methods allow the measurement of (13)C/(14,15)N distances, with (13)C observation, in uniformly (13)C-labeled samples. Furthermore, we provide analytical solutions for the S-REDOR and S-RESPDOR dephasing curves. These solutions facilitate the measurement of hetero-nuclear distances from experimental data. PMID- 20577688 TI - Experimental determination of the Onsager coefficients of transport for Ce(0.8)Pr(0.2)O(2-delta). AB - For a mixed oxide-ion and electron conducting oxide, with oxygen vacancies (V(O)) and electrons (e') or holes (h ) as charge carriers, a flux of (V(O)) (J(i)) can in principle be driven, not only directly by its own electrochemical potential gradient (inverted Delta eta(i)), but also indirectly by that of electrons (inverted Delta eta(e)), and vice versa for the flux of electrons (J(e)). It is common practice to assume that electrons and mobile ions migrate independently, despite the lack of experimental evidence in support of this. Here, all the Onsager coefficients, including the cross coefficients, have been measured for Ce(0.8)Pr(0.2)O(2-delta) within the a(O(2)) range 10(-21)-1 at 800 degrees C, using local ionic and electronic probes in a four-probe configuration. The cross coefficients of transport were found to be negligible in comparison to the direct coefficients in the a(O(2)) range 10(-21)-10(-4), but of the same order of magnitude as the direct coefficients for high a(O(2)) values (10(-2)-1). This is in contrast to the commonly used assumption that the two types of carriers migrate independently, i.e. that L(ie) = 0. PMID- 20577689 TI - Impact of changes in nutrient inputs to the water quality of the shallow Haapsalu Bay, the Baltic Sea. AB - This study evaluated the impact of socio-economic and lifestyle changes on nutrient loads and water quality in Haapsalu Bay, the Baltic Sea between 1995 1996 and 2003-2004. Monthly monitoring data of water quality in four rivers discharging to the bay and seawater at five sea stations were used. External input of TN to the bay remained almost unchanged during the study period despite of the somewhat higher riverine load that was explained by intensified agriculture. The TP input decreased by approximately 45% due to the decrease in river and point source loads. Point sources contribute about one-third of the P load to the bay. An overall decreasing gradient from the rivers to the mouth of the bay was observed both for TP and TN concentrations indicating probable removal of these elements from the water column along the east-west transect. In order to keep the TN/TP ratio within the range that suppresses eutrophication in the bay, further efforts must be implemented to reduce point source phosphorus load. PMID- 20577690 TI - Proton mobility through a second order phase transition: theoretical and experimental study of LaNbO4. AB - The gradual change in the crystal structure of the high temperature proton conductor LaNbO(4) through a second order phase transition and its relation to the activation enthalpy of mobility of protons have been studied by means of first principles calculations and conductivity measurements. The computations have revealed that protons diffuse by an inter-tetrahedral mechanism where the activation enthalpies of mobility are 39 and 60 kJ mol(-1) in tetragonal and monoclinic LaNbO(4), respectively. The activation enthalpy of mobility of protons for tetragonal LaNbO(4), determined from the conductivity curve, is 35 kJ mol( 1). Below the transition temperature the conductivity curve bends; initially dropping off steeply, followed by a less steep decrease towards lower temperatures. The bend in the conductivity curve at the onset of the phase transition in LaNbO(4) should not be given the traditional interpretation as an abrupt change in the activation enthalpy of mobility. After application of the proper analysis of the conductivity data, which takes the second order transition into account, the activation enthalpy of mobility of protons is found to continuously increase with increasing monoclinic angle at decreasing temperature, reaching approximately 57 kJ mol(-1) at 205 degrees C for the end monoclinic phase. PMID- 20577691 TI - The interface bonding and orientation of a quinonoid zwitterion. AB - We have investigated the interaction and orientation of a strongly dipolar zwitterionic p-benzoquinonemonoimine-type molecule, with a large intrinsic dipole of 10 Debye, on both conducting and on polar insulating substrates. Specifically, we deposited (6Z)-4-(butylamino)-6-(butyliminio)-3-oxocyclohexa-1,4-dien-1-olate C(6)H(2)([horiz bar, triple dot above]NHR)(2)([horiz bar, triple dot above]O)(2) where R = n-C(4)H(9), on both gold and ferroelectric lithium niobate surfaces. An influence of both transient and static electric dipoles on the zwitterionic adsorbate has been observed. For adsorption on gold, we find that the molecule bonds to the surface through the nitrogen atoms, forming films that remain fairly uniform down to thicknesses in the 1 nm range. Adsorption of this zwitterionic compound from solution on insulating, periodically poled ferroelectric lithium niobate substrates, showed preferential adsorption on one type of ferroelectric domain. For both gold and the lithium niobate substrates, the zwitterion adopts a preferential orientation with the plane of its "C(6) core" along the surface normal. This simplified geometry of strong dipole alignment provides a symmetry simplification allowing better identification of the vibrational modes responsible for Frank-Condon scattering revealed in the fine spectroscopic signature in the photoemission spectrum. PMID- 20577692 TI - Evolution of metallic screening in small metal clusters probed by PCI-Auger spectroscopy. AB - Excitation-energy dependent Auger spectra of small copper clusters supported by a thin silica layer have been measured as function of cluster size. The Auger kinetic energy of the clusters clearly changes with the excess energy of the emitted photoelectron while not for the bulk. The kinetic energy shift is attributed to post-collision interaction (PCI) and exhibits a reduced metallic screening ability of small Cu-clusters. The spectroscopic data reveal an evolution from a long-range Coulomb-like interaction to a short-range "screened" electrostatic interaction within the sub-nm range. The data show that core electron spectroscopy such as PCI-Auger measurements can be used as a general tool to follow the metallic character of supported clusters. PMID- 20577693 TI - Least squares in calibration: dealing with uncertainty in x. AB - The least-squares (LS) analysis of data with error in x and y is generally thought to yield best results when carried out by minimizing the "total variance" (TV), defined as the sum of the properly weighted squared residuals in x and y. Alternative "effective variance" (EV) methods project the uncertainty in x into an effective contribution to that in y, and though easier to employ are considered to be less reliable. In the case of a linear response function with both sigma(x) and sigma(y) constant, the EV solutions are identically those from ordinary LS; and Monte Carlo (MC) simulations reveal that they can actually yield smaller root-mean-square errors than the TV method. Furthermore, the biases can be predicted from theory based on inverse regression--x upon y when x is error free and y is uncertain--which yields a bias factor proportional to the ratio sigma(x)(2)/sigma(xm)(2) of the random-error variance in x to the model variance. The MC simulations confirm that the biases are essentially independent of the error in y, hence correctable. With such bias corrections, the better performance of the EV method in estimating the parameters translates into better performance in estimating the unknown (x(0)) from measurements (y(0)) of its response. The predictability of the EV parameter biases extends also to heteroscedastic y data as long as sigma(x) remains constant, but the estimation of x(0) is not as good in this case. When both x and y are heteroscedastic, there is no known way to predict the biases. However, the MC simulations suggest that for proportional error in x, a geometric x-structure leads to small bias and comparable performance for the EV and TV methods. PMID- 20577694 TI - Efficient energy conversion of nanotube/nanowire-based solar cells. AB - Hybrid photoelectrochemistry and heterojunction solar cells made from carbon nanotubes and silicon nanowires show high energy conversion efficiencies of up to 6%. PMID- 20577695 TI - Colloidal graphene oxide/polyaniline nanocomposite and its electrorheology. AB - A nanocomposite of colloidal graphene oxide (CGO) and polyaniline (PANI) was fabricated via in situ oxidation polymerization in the presence of CGO prepared via a modified Hummers method without a dopant, in which the graphene oxide was individually exfoliated. Its electrorheological properties and other physical characteristics were studied. PMID- 20577696 TI - Intrinsic lifetimes of the Soret bands of the free-base tetraphenylporphine (H(2)TPP) and Cu(ii)TPP in the condensed phase. AB - Soret band lifetimes of the free-base tetraphenylporphine (H(2)TPP) and Cu(ii) tetraphenylporphine (Cu(II)TPP) at 408 nm have been directly measured with femtosecond (fs) resolution using the fluorescence-upconversion technique for the first time, giving tau = 68 +/- 15 and 63 +/- 15 fs, respectively, in benzene solvent. PMID- 20577697 TI - Click-based synthesis and proteomic profiling of lipstatin analogues. AB - Using click chemistry to enable both structural diversity and proteome profiling within a natural product derived library, two out of nineteen lipstatin analogues showed similar activity to Orlistat against fatty acid synthase (FAS), but with an improved ability to induce tumour cell death. PMID- 20577698 TI - Clicked dipicolinic antennae for lanthanide luminescent probes. AB - 4-Triazolyl-dipicolinic acids, prepared efficiently by CuAAC, proved to act as efficient antennae for optical lanthanide probes containing Eu(3+) or Tb(3+), under linear and non linear excitations (one, two and three photons provided by laser induced luminescence). The versatility offered by the substitution of the triazole subunit is, in addition, useful for covalent linkage to slide glass providing luminescent films. PMID- 20577699 TI - Plasma metabolic profiling reveals age-dependency of systemic effects of green tea polyphenols in mice with and without prostate cancer. AB - Green tea polyphenols (GTP) have been widely investigated for their potential to prevent prostate cancer. However, results from epidemiological and clinical studies are equivocal. Studies in the TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) mouse suggest that the chemopreventive efficacy of GTP is higher in young animals with early stages of carcinogenesis than in old ones. Here, effects of GTP on prostate carcinogenesis in TRAMP mice were assessed by comparing pathological changes with (1)H-NMR metabolic profiling of plasma and extracts of prostate tissue. Mice received 0.05% GTP in their drinking water for 4 or 25 weeks after weaning. Age-matched wild-type mice were included in the study in order to establish differences in GTP effects between normal and TRAMP mice. Dietary GTP did not markedly alter prostate carcinogenesis as reflected by pathology and prostate tissue metabolic profile. However, a systemic effect of GTP consumption was observed in young mice, regardless of genotype. Plasma lipid signals were decreased in 8 week old mice which received GTP compared to age matched controls by 19, 61, 27, 34 and 15% (p extracellular > obligate intracellular bacteria. Results further show that the obligate intracellular bacteria that host switch have a higher mobile DNA gene density than the obligate intracellular bacteria that are vertically transmitted. Second, while bacteria from the three ecological niches differ in their average mobile DNA contents, the ranges of mobile DNA found in each category overlap a surprising extent, suggesting bacteria with different lifestyles can tolerate similar amounts of mobile DNA. Third, mobile DNA gene densities increase with genome size across the entire dataset, and the significance of this correlation is dependent on the obligate intracellular bacteria. Further, mobile DNA gene densities do not correlate with evolutionary relationships in a 16S rDNA phylogeny. These findings statistically support a compelling link between mobile element evolution and bacterial ecology. PMID- 20577744 TI - Impact of oral anticoagulation on morbidity of transurethral resection of the prostate. AB - AIM: To assess the impact of oral anticoagulation (OA) on morbidity of transurethral resection of the prostate (TURP). OA included warfarin and platelet aggregation inhibitors (PAI). PATIENTS AND METHOD: Multicenter analysis of patients operated for symptomatic benign prostatic hyperplasia (BPH) by TURP. Patients under OA were compared to those with no OA. RESULTS: Out of 612 patients included in the analysis, 206 (33%) were on OA prior surgery (55 warfarin, 142 PAI, and 9 warfarin and PAI). No patient continued warfarin and clopidogrel during the operating period. Patients under OA were significantly older (75 vs. 71 yo, P < 0.001), had larger prostate volume (56 vs. 49 ml, P = 0.05), and had higher rate of bladder catheter prior surgery (26 vs. 17%, P = 0.02). At 3 months follow-up, patients in the OA group had a higher weight of resected tissue (24 vs. 21.7 g, P < 0.001), a longer duration of hospitalization (6.4 vs. 4.7 days P < 0.001), a higher rate of bladder clots (13 vs. 4.7%, P < 0.001), red cell transfusion (1.9 vs. 1.0%, P = 0.026), late hematuria (15.0 vs. 8.4%, P = 0.004), and thromboembolic events (2.4 vs. 0.7, P = 0.02). In multivariable analysis, OA status was the sole independent parameter associated with bladder clots (P = 0.004) and with late hematuria (P = 0.03). CONCLUSION: OA had a significant and independent impact on TURP outcome in terms of bleeding complications. This data could be used for treatment decision and for patient's information prior BPH surgery. PMID- 20577743 TI - Defective imprint resetting in carriers of Robertsonian translocation Rb (8.12). AB - Meiotic silencing of unsynapsed chromatin (MSUC) occurs in the germ cells of translocation carriers and may cause meiotic arrest and infertility. We hypothesized that if bypassing meiotic checkpoints MSUC may cause epigenetic defects in sperm. We investigated the meiotic behavior of the Robertsonian translocation Rb (8.12) in mice. The unsynapsed 8 and 12 trivalent was associated with the XY body during early and mid-pachynema in heterozygous Rb (8.12) carriers, suggesting possible silencing of pericentromeric genes, such as the Dnmt3a gene. In wild-type mice, DNMT3A protein showed a dramatic accumulation in the nucleus during the mid-pachytene stage and distinct association with the XY body. In translocation carriers, DNMT3A was less abundant in a proportion of pachytene spermatocytes that also had unsynapsed pericentromeric regions of chromosomes 8 and 12. The same mice had incomplete methylation of the imprinted H19 differentially methylated region (DMR) in sperm. We propose that impaired H19 imprint establishment results from lack of synapsis in chromosomes 8 and 12 probably through transient silencing of a chromosome 8 or 12 gene during pachynema. Furthermore, our findings support the notion that imprint establishment at the H19 locus extends into pachynema. PMID- 20577745 TI - [Familial exudative vitreoretinopathy]. AB - Familial exudative vitreoretinopathy (FEVR) is an autosomal dominant inherited disease with a penetrance of nearly 100% and is mostly found in Asia. The most important sign is a temporal avascular retina with pathologically changed vessels combined with a temporal dragging of the disk and a heterotopy of the macula. In contrast to retinopathy of prematurity, only full-term children without oxygen therapy are affected. Clinical severity is highly variable. A stage of an asymptomatic gene carrier with peripheral ischemia only visible on angiography up to a massive deterioration of vision because of a combined tractional and rhegmatogenous retinal detachment is possible. All stages with intra- or subretinal exudates require therapy. First-line therapy is the coagulation of the leaky vessels to reduce the exudation. In addition cryocoagulation is possible. Advanced stages with complex retinal detachments usually require a vitrectomy to prevent further loss of visual function. PMID- 20577746 TI - Stapled anastomosis for anterior resection is safe even after previous stapled haemorrhoidectomy--a report of five cases. AB - INTRODUCTION: Stapled haemorrhoidectomy has become popular for the treatment of symptomatic bleeding or prolapsing piles. There are concerns about the safety of another stapled low colorectal anastomosis after rectal resection if a patient who has had previous stapled haemorrhoidectomy subsequently develops colorectal neoplasia requiring an anterior resection. METHODS: A retrospective review of patients who underwent stapled haemorrhoidectomy and subsequently had anterior resection from 1999 to 2008 was performed. RESULTS: Five patients (all male) were found to have distal sigmoid or rectal tumours on surveillance colonoscopy after stapled haemorrhoidectomy. Median age was 65 years (range 58-71). All underwent anterior resection with stapled end-to-end colorectal anastomosis at median of 29 months (range 18-60 months) after the initial stapled haemorrhoidectomy. Median anastomotic height was 12 cm (range 1-12 cm). A defunctioning ileostomy was created for three out of five patients. All the colorectal anastomoses healed uneventfully. CONCLUSIONS: Stapled colorectal anastomosis may be safely performed after previous stapled haemorrhoidectomy. PMID- 20577747 TI - [Problems associated with treating ocular disease in underlying inflammatory rheumatic disease]. AB - Ocular findings can be very typical for general disorders associated with rheumatological diseases. Of these ocular diseases, scleritis and uveitis are of particular significance. The present article discusses and attempts to solve the problems which can be seen when ocular inflammation is associated with rheumatological disorders. The identification of "uveitis" should not be sufficient to initiate diagnosis and therapy, but rather its localisation and, where possible, also its etiology should be known. These can usually be found with good clinical investigation and careful patient history. Only rarely are ocular and rheumatological inflammation active at the same time, as will be discussed later using HLA-B27-associated uveitis and juvenile idiopathic arthritis-associated uveitis as examples. It is important in the case of ocular inflammation that the indication for treatment be made by an ophthalmologist. Finally, the role of the rheumatologist in the treatment of this patient group will be described in detail. PMID- 20577748 TI - Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. AB - PURPOSE: To compare the effect of letrozole with laparoscopic ovarian diathermy (LOD) for ovulation induction in clomiphene citrate (CC) resistant women with polycystic ovary syndrome (PCOS). METHODS: Two hundred and sixty anovulatory women with CC-resistant PCOS were selected in this randomized controlled trial. Group A (n = 128) received 2.5 mg letrozole daily for 5 days for up to six cycles. Group B (n = 132) underwent LOD with 6 months follow-up. Outcome measures were ovulation rate, midcycle endometrial thickness, pregnancy, miscarriage and live birth rates. RESULTS: Ovulation occurred in 335/512 cycles (65.4%) in letrozole group and 364/525 cycles (69.3%) in LOD group without significant difference between both groups. Resumption of regular menstruation was similar in both treatment groups. A significant increase in midcycle endometrial thickness was observed in letrozole group (8.8 +/- 1.1 mm vs. 7.9 +/- 1.2 mm) (P < 0.05). Pregnancy rate was similar in both groups (15.6 vs. 17.5%). There were no statistical significant differences as regards miscarriage and live birth rates between both groups. No multiple pregnancy or ovarian hyperstimulation occurred in either group. CONCLUSION: Letrozole and LOD are equally effective for inducing ovulation and achieving pregnancy in CC-resistant PCOS patients. PMID- 20577749 TI - Does intercourse during menses increase the risk for sexually transmitted disease? AB - Intercourse during menses is an acceptable sexual behavior that is practiced by 3 30% of sexually active women. This pattern of sexual behavior may contribute to transmission of some sexually transmitted disease. Yet, intercourse during menses is probably not associated with increased risk for pelvic inflammatory disease. The above-mentioned susceptibility for increased risk for sexually transmitted disease in women engaged in sexual intercourse during menses could be explained by the sexual behavior itself and/or by hampered response of innate immune system during menses. Still, while counseling couples about intercourse during menses, its potential advantages should be weighed against possible disadvantages. PMID- 20577750 TI - The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause. AB - PURPOSE: The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA). METHODS: A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 MUg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed. RESULTS: After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI. CONCLUSION: Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies. PMID- 20577751 TI - Pregnancy outcome in women with autoimmune hepatitis. AB - INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic disease of unknown cause, characterized by progressive hepatocellular inflammation and necrosis, frequently leading to cirrhosis. AIH usually affects young women and may influence fertility and pregnancy in them. Nearly 200 pregnancies have been reported so far in the world literature in women with AIH, and no definite guidelines have been established. We hereby report our experience of four pregnancies in women with definite diagnosis of AIH. MATERIALS AND METHODS: We studied the maternal and perinatal outcome of four women with AIH. The medical history was recorded in detail. The pregnancies were allowed to continue with careful fetal and maternal surveillance. Antenatal complications, disease course during pregnancy, intrapartum maternal fetal events, mode of delivery, and perinatal outcome were noted. RESULTS: All four patients had preterm labor: three had vaginal delivery and cesarean was done in one due to breech presentation with preterm rupture of membranes. All the infants were live born with birth weight appropriate for gestational age and were born with good Apgar scores and no congenital malformation. The incidence of post partum hemorrhage was 25% and so was the maternal mortality. CONCLUSION: Successful pregnancy outcome in patients with well-controlled AIH seems to be a realistic expectation with careful monitoring jointly by the Obstetricians and Hepatologists, especially in the post partum period. Steroids seem to be the safe alternative as immunosuppressant therapy although azathioprine has also been seen to be generally safe for mother or baby. PMID- 20577752 TI - Diagnosis and treatment of iron-deficiency anaemia during pregnancy and postpartum. AB - INTRODUCTION: Iron-deficiency anaemia during pregnancy and postpartum occurs frequently and may lead to severe maternal and foetal complications. New treatment regimens include intravenous iron administration in particular clinical situations. The aim of the study was to determine optimal diagnostic and therapeutic approaches to iron-deficiency anaemia during pregnancy and postpartum. METHODS: The evidence from data available from published studies and recommendations regarding diagnosis and treatment were reviewed. As conclusions, recommendations are given by an expert panel. RESULTS: During pregnancy, oral iron therapy is given as first-line treatment. In cases with lack of efficacy, unwarranted side effects or very low haemoglobin values, intravenous iron treatment with iron carboxymaltose is a preferable alternative, although data regarding safety are limited. In the postpartum period, haemoglobin values less than 95 g/L are treated ideally by intravenous carboxymaltose, leading to more rapid haemoglobin recovery. CONCLUSION: New intravenous iron preparations such as iron carboxymaltose have an excellent efficacy, side effect profile and advantages as compared to oral iron preparations for particular clinical indications. PMID- 20577753 TI - Piezosurgery versus microdrill in intact canal wall mastoidectomy. AB - Piezosurgery is a recently developed system for cutting bone with microvibrations. The objectives of the present study were to report our experience with the piezoelectric device in the intact canal mastoidectomy, and to compare the results with traditional method by means of microdrill. A non randomized controlled trial was undertaken on 60 intact canal wall mastoidectomy performed using the piezoelectric device (30 patients) or the microdrill (30 patients). Before 1 month and 1 year after surgery, all the patients underwent the following instrumental examinations: otomicroscopic evaluation of the tympanic membrane and external auditory duct, bone conduction threshold audiometry, tympanometry, transient-evoked otoacoustic emissions with linear click emission, distortion product otoacoustic emissions, auditory brainstem response (ABR) by MK 12-ABR screener with natus-ALGO2e (Amplifon, Milan, Italy), and electronystamographic recording. The piezoelectric device is proved to be effective in sclerotic and pneumatic mastoid, with an excellent control and without side effects on the adjacent structures of the middle and inner ear (lateral sinus, facial nerve, and/or dura mater). The operation time has been the same as compared with microdrill, and the average hospital stay was significantly (p < 0.05) shorter. Postoperatively, all patients had uneventful recovery with no evidence of audiovestibular deficit or side effects. Our experience highlights the safety of the piezoelectric device on the anatomic structures of the middle and inner ear, and demonstrates its efficiency in terms of cutting precision and healing process. PMID- 20577754 TI - Assessing audiological, pathophysiological and psychological variables in tinnitus patients with or without hearing loss. AB - The aim of this work is to study the characteristics of tinnitus both in normal hearing subjects and in patients with hearing loss. The study considered tinnitus sufferers, ranging from 21 to 83 years of age, who were referred to the Audiology Section of Palermo University in the years 2006-2008. The following parameters were considered: age, sex, hearing threshold, tinnitus laterality, tinnitus duration, tinnitus measurements and subjective disturbance caused by tinnitus. The sample was divided into Group1 (G1), 115 subjects with normal hearing, and Group2 (G2), 197 subjects with hearing loss. Especially for G2, there was a predominance of males compared to females (P = 0.011); the highest percentage of tinnitus resulted in the decades 61-70 and >70 with a significant difference for G2 demonstrating that the hearing status and the elderly represent the principal tinnitus-related factors (P < 0.0001). The hearing impairment resulted in most cases of sensorineural hearing loss (SNHL) type and was limited to the high frequencies; the 72.1% of the patients with SNHL had a high-pitched tinnitus, while the 88.4% of the patients with a high-frequency SNHL had a high-pitched tinnitus (P < 0.0001). As to the subjective discomfort, the catastrophic category was the most representative among G1 with a significant difference between the two groups; no correlation was found between the level of tinnitus intensity and the tinnitus annoyance confirming the possibility that tinnitus discomfort is elicited by a certain degree of psychological distress as anxiety, depression, irritability and phobias. PMID- 20577755 TI - Corneal flap assessment with Rondo microkeratome in laser in situ keratomileusis. AB - PURPOSE: To assess the accuracy of flap thickness in laser in situ keratomileusis (LASIK) with Rondo, Wavelight AG microkeratome and to examine factors that can influence flap thickness (FT). SETTING: The study took place at the Laser & Ophthalmos Eye Clinic, Thessaloniki, Greece. MATERIAL AND METHODS: Three hundred and sixty eyes from 180 patients underwent LASIK with Rondo microkeratome. Three surgeons (A, B and C) performed all surgeries with no previous experience of Rondo microkeratome. All patients were treated with the 130 MUm plate. Central corneal thickness (CCT) and stromal bed thickness were measured by Scheimpflug and ultrasound pachymetry. Right eye (OD) was treated first. RESULTS: Mean FT for OD: 120 +/- 19 MUm (range 69-158 MUm); for left eye (OS): 106 +/- 17 MUm (range 70-147 MUm). Flaps in OD were significantly thicker than in OS (p < 0.001). FT was significantly correlated to the keratometric reading (K): r = 0.121; p = 0.02. No correlation was found between FT and CCT or between FT and the attempted refractive correction (SE) (p > 0.14). Mean FT was significantly lower than the manufacturer's 130 MUm specification (Mean FT = 113 +/- 19 MUm; p < 0.001). FT between surgeons A, B and C was significantly different (analysis of variance between surgeons; p < 0.001). Scheimpflug and ultrasound CCT measurements were significantly correlated (r = 0.921; p < 0.001) with ultrasound measuring an average 4.5 MUm higher than Scheimpflug (CCT (Oculyzer) = 553.96 +/- 27 MUm; CCT (Ultrasound) = 558.45 +/- 28 MUm). Mean flap diameter was 9.2 +/- 0.2 mm. CONCLUSIONS: FT with Rondo microkeratome was significantly influenced by the mean preoperative K reading. First treated eye was significantly thicker than the fellow left eye, while both were significantly lower than the recommended 130 MUm thickness. Gaining basic experience of Rondo microkeratome required an average of 90 flaps/surgeon. PMID- 20577756 TI - Comparison between Pascal dynamic contour tonometer and Goldmann applanation tonometer after different types of refractive surgery. AB - BACKGROUND: To evaluate and compare the recorded IOP values of the Pascal dynamic contour tonometer (PDCT) and the Goldmann applanation tonometer (GAT) after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). METHODS: Three groups of 84, 182 and 43 patients each were treated by PRK for myopia, LASIK for myopia and LASIK for hyperopia respectively. Intraocular pressure (IOP) measurements were performed in all eyes 1 day before and 1, 3, 6 and 12 months after treatment with PDCT and GAT. Ultrasound pachymetry was performed in all eyes preoperatively and at 1st month postoperatively. RESULTS: Preoperatively and postoperatively, GAT readings were lower than PDCT in all groups (all p < 0.05). Postoperatively in the PRK group, compared to the preoperative value, the mean differences of IOP recorded with GAT at 1st, 3rd, 6th and 12th month were -1.4 mmHg, -1.7 mmHg, -1.7 mmHg and -1.9 mmHg respectively (all p < 0.05). In the myopic LASIK group; the corresponding values with GAT were -3.6 mmHg, -3.6 mmHg, -3.6 mmHg and -3.5 mmHg (all p < 0.05), while in the hyperopic LASIK group the corresponding values were -1.1 mmHg, -0.7 mmHg, 1.1 mmHg and -0.9 mmHg (all p < 0.05). The mean IOP difference (GAT-PDCT) for myopic PRK, myopic LASIK and hyperopic LASIK were respectively -3.8 mmHg, -4.1 mmHg and -1.5 mmHg at the 12-month follow-up. No statistically significant changes were found for any group with the PDCT. CONCLUSIONS: GAT-determined IOP values were significant lower at all time-points after hyperopic LASIK, as well as myopic PRK or LASIK. The Pascal tonometry values remained unaffected for all groups. PMID- 20577757 TI - Use of heart rate monitoring for an individualized and time-variant decompression model. AB - Individual differences, physiological pre-conditions and in-dive conditions like workload and body temperature have been known to influence bubble formation and risk of decompression sickness in diving. Despite this fact, such effects are currently omitted from the decompression algorithms and tables that are aiding the divers. There is an apparent need to expand the modeling beyond depth and time to increase safety and efficiency of diving. The present paper outlines a mathematical model for how heart rate monitoring in combination with individual parameters can be used to obtain a customized and time-variant decompression model. We suggest that this can cover some of the individual differences and dive conditions that are affecting bubble formation. The model is demonstrated in combination with the previously published Copernicus decompression model, and is suitable for implementation in dive computers and post dive simulation software for more accurate risk analysis. PMID- 20577758 TI - Cell-free plasma DNA and purine nucleotide degradation markers following weightlifting exercise. AB - The present study aimed to investigate the acute effects of a single bout of high intensive strength training on the production of cell-free plasma DNA (cf-DNA), as well as on the degradation of purine nucleotides as assessed by the concentration of xanthine (XA) and hypoxanthine (HX) in urine and serum. Twelve trained weightlifters performed six sets of six lifting exercises with 90-95% of the one repetition maximum. Blood samples and urine were obtained 1 h before training, immediately after finishing the exercise session and following 2 h of recovery. Cf-DNA, HX, and XA (in serum) significantly increased (P < 0.05-P < 0.001) immediately after heavy lifting exercise when compared with baseline levels, and significantly decreased (P < 0.05-P < 0.001) after 2 h of recovery. These results indicate that, cf-DNA and oxypurines might be relevant biomarkers for cellular damage, mechanical, energetic, and/or ischemic stress in context with exercise. PMID- 20577759 TI - Laparoscopic appendectomy using a single polymeric clip to close the appendicular stump. AB - BACKGROUND: The aim of this study was to evaluate the feasibility, morbidity, and cost-effectiveness of the closure of the appendicular stump with a single non absorbable polymeric clip compared with the closure of the appendicular stump with a stapler. METHODS: From January 2009 to December 2009, 82 patients, 31 males and 51 females (mean age of 35.4 years; range of 17 to 79 years), were included in this prospective, non-randomized trial. In 56 patients, the appendicular stump was closed by staplers, and in 26 patients, a single Hem-o-lok MLX polymeric clip was applied. The data collected included age, sex, time of surgery, costs, time of hospitalization, day-time of surgery, complications, and preoperative white blood count (WBC) and c-reactive protein (CRP). RESULTS: There were no differences between the two groups regarding age, sex, WBC, CRP, and time of hospitalization. Time of surgery was longer in the clip group due to the introductory phase. Morbidity did not differ significantly and was highly acceptable in both groups. The costs of one set of Hem-o-lock clips were negligible compared to staplers (19.94 euros versus 356.43 euros). CONCLUSIONS: The use of a single non-absorbable polymeric clip is easy to use even for surgical trainees; it is safe and cost-effective. We suggest the use of a single clip for the closure of the appendicular stump as the standard procedure in laparoscopic appendectomy whenever possible. PMID- 20577760 TI - Fibrodysplasia ossificans progressiva (FOP): watch the great toes! AB - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder and the most disabling condition of heterotopic (extraskeletal) ossification in humans. Extraskeletal bone formation associated with inflammation preceding the osseous conversion usually begins in the first decade, predominantly in the head, neck, and shoulders. All patients have malformed great toes. Most patients have a spontaneous mutation of the ACVR1 gene. We report a 17-year-old girl with malformed great toes who had her first episode of heterotopic ossification and impaired mobility of the left hip at the age of 13 years. No inflammatory fibroproliferative masses preceded the onset of heterotopic ossification. Radiographic studies demonstrated myositis ossificans, but failure to associate the great toe malformation with heterotopic ossification led to a failure to diagnose FOP. She underwent repeated and unnecessary operative procedures to remove a recurrent lesion. FOP was finally suspected when the great toe malformation was correlated with the trauma-induced heterotopic ossification. Genetic analysis confirmed the presence of the classic FOP mutation (ACVR1 c.617G>A; R206H). This case highlights the importance of examining the great toes in anyone with heterotopic ossification. The association of malformations of the great toe with heterotopic ossification in all cases of classic FOP will lead to prompt clinical diagnosis and the prevention of iatrogenic harm. PMID- 20577761 TI - The actin multigene family in Populus: organization, expression and phylogenetic analysis. AB - Despite the significance of actin in plant growth and development, little is known of the structure, expression and evolution of the actin gene family in woody plants. In this study, we systematically examined the diversification of the actin gene family in Populus by integrating genomic organization, expression, and phylogeny data. Genome-wide analysis of the Populus genome indicated that actin is a multigene family consisting of eight members, all predicted to encode 377-amino acid polypeptides that share high sequence homology ranging from 94.2 to 100% identity. Microarray and real-time PCR expression analysis showed that the PtrACT family members are differentially expressed in different tissues, exhibiting overlapping and unique expression patterns. Of particular interest, all PtrACT genes have been found to be preferentially expressed in the stem phloem and xylem, suggesting that poplar PtrACTs are involved in the wood formation. Gene structural and phylogenetic analyses revealed that the PtrACT family is composed of two main subgroups that share an ancient common ancestor. Extremely high intraspecies synonymous nucleotide diversity of pi(syn) = 0.01205 was detected, and the pi(non-syn)/pi(syn) ratio was significantly less than 1; therefore, the PtACT1 appears to be evolving in Populus, primarily under purifying selection. We demonstrated that the actin gene family in Populus is divided into two distinct subgroups, suggesting functional divergence. The results reported here will be useful in conducting future functional genomics studies to understand the detailed function of actin genes in tree growth and development. PMID- 20577762 TI - Trophic ecology of the invasive argentine ant: spatio-temporal variation in resource assimilation and isotopic enrichment. AB - Studies of food webs often employ stable isotopic approaches to infer trophic position and interaction strength without consideration of spatio-temporal variation in resource assimilation by constituent species. Using results from laboratory diet manipulations and monthly sampling of field populations, we illustrate how nitrogen isotopes may be used to quantify spatio-temporal variation in resource assimilation in ants. First, we determined nitrogen enrichment using a controlled laboratory experiment with the invasive Argentine ant (Linepithema humile). After 12 weeks, worker delta(15)N values from colonies fed an animal-based diet had delta(15)N values that were 5.51% greater compared to colonies fed a plant-based diet. The shift in delta(15)N values in response to the experimental diet occurred within 10 weeks. We next reared Argentine ant colonies with or without access to honeydew-producing aphids and found that after 8 weeks workers from colonies without access to aphids had delta(15)N values that were 6.31% larger compared to colonies with access to honeydew. Second, we sampled field populations over a 1-year period to quantify spatio-temporal variability in isotopic ratios of L. humile and those of a common native ant (Solenopsis xyloni). Samples from free-living colonies revealed that fluctuations in delta(15)N were 1.6-2.40/00 for L. humile and 1.8-2.90/00 for S. xyloni. Variation was also detected among L. humile castes: time averaged means of delta(15)N varied from 1.2 to 2.50/00 depending on the site, with delta(15)N values for queens >= workers > brood. The estimated trophic positions of L. humile and S. xyloni were similar within a site; however, trophic position for each species differed significantly at larger spatial scales. While stable isotopes are clearly useful for examining the trophic ecology of arthropod communities, our results suggest that caution is warranted when making ecological interpretations when stable isotope collections come from single time periods or life stages. PMID- 20577763 TI - Carbon dioxide exchange and canopy conductance of two coniferous forests under various sky conditions. AB - Sky conditions play an important role in the Earth's climate system and CO(2) uptake by plants. We used eddy covariance and meteorological data, including global and diffuse photosynthetic photon flux density (PPFD), recorded over the 2008 and 2009 growing season at two Sitka spruce [Picea sitchensis (Bong.) Carr.] forest sites in northern Britain, in order to establish relationships between physiological properties under diverse sky conditions, i.e. (1) sunny, (2) cloudy, and (3) overcast, and several canopy activity-related properties. These properties are: (1) response to PPFD, (2) photosynthetic light use efficiency, and (3) canopy stomatal conductance. We found that Sitka spruce forests utilise PPFD in a more efficient way when solar radiation is dominated by diffuse radiation. Furthermore, our results show that diffuse radiation enhances canopy stomatal conductance, an effect which may be the result of both blue light enrichment within the canopy and the reduction in vapour pressure deficit during cloudy and overcast weather. Diffuse radiation does not only influence short-term (hourly, daily, monthly) canopy activity but also long-term forest growth. PMID- 20577764 TI - Slowed decomposition is biotically mediated in an ectomycorrhizal, tropical rain forest. AB - Bacteria and fungi drive the cycling of plant litter in forests, but little is known about their role in tropical rain forest nutrient cycling, despite the high rates of litter decay observed in these ecosystems. However, litter decay rates are not uniform across tropical rain forests. For example, decomposition can differ dramatically over small spatial scales between low-diversity, monodominant rain forests, and species-rich, mixed forests. Because the climatic patterns and soil parent material are identical in co-occurring mixed and monodominant forests, differences in forest floor accumulation, litter production, and decomposition between these forests may be biotically mediated. To test this hypothesis, we conducted field and laboratory studies in a monodominant rain forest in which the ectomycorrhizal tree Dicymbe corymbosa forms >80% of the canopy, and a diverse, mixed forest dominated by arbuscular mycorrhizal trees. After 2 years, decomposition was significantly slower in the monodominant forest (P < 0.001), but litter production was significantly greater in the mixed forest (P < 0.001). In the laboratory, we found microbial community biomass was greater in the mixed forest (P = 0.02), and the composition of fungal communities was distinct between the two rain forest types (P = 0.001). Sequencing of fungal rDNA revealed a significantly lower richness of saprotrophic fungi in the monodominant forest (19 species) relative to the species-rich forest (84 species); moreover, only 4% percent of fungal sequences occurred in both forests. These results show that nutrient cycling patterns in tropical forests can vary dramatically over small spatial scales, and that changes in microbial community structure likely drive the observed differences in decomposition. PMID- 20577765 TI - Tracheal intubation by paramedics under limited indication criteria may improve the short-term outcome of out-of-hospital cardiac arrests with noncardiac origin. AB - PURPOSE: It is not clear whether advanced airway management (AAM) with an endotracheal tube (ET) by paramedics may improve the outcome of out-of-hospital cardiac arrest (OHCA) compared with the use of a bag-valve-mask device (BVMD) and other AAM devices. METHODS: We analyzed 2,586 adult cases of OHCA without administration of adrenaline, witnessed or recognized by citizens in subjects transported to hospital by paramedics between 1 July 2004 and 31 March 2008 in Ishikawa, Japan, to determine whether AAM with an ET used under limited indication criteria may improve the outcome of OHCA. RESULTS: The airway was managed with an ET in 263 cases, other AAM devices in 660 cases, and a BVMD in 1,539 cases. The AAM failed or was discontinued in 124 cases, which were excluded from the analysis. The incidence of sustained return of spontaneous circulation (ROSC) was significantly higher in cases of AAM with an ET (30%) than in AAM with other devices (20.2%) and in the standard procedure with a BVMD (21.3%). The AAM with an ET did not significantly affect 1-year survival. Multiple regression analysis indicated that tracheal intubation (odds ratio = 1.503, 95% confidence interval 1.081-2078), but not patient management by paramedics qualified for ET use, was an independent factor associated with sustained ROSC. CONCLUSION: When subjects with difficult airway are excluded, tracheal intubation according to the limited indication criteria and well-organized protocol in Japan may improve the short-term outcome of OHCA of noncardiac origin. A large prospective study is needed to determine the general effects of tracheal intubation on the long-term outcome of OHCA with disturbed ventilation. PMID- 20577766 TI - Biomechanical and histological evaluation of an expandable pedicle screw in osteoporotic spine in sheep. AB - Transpedicular fixation can be challenging in the osteoporotic spine as reduced bone mineral density compromises the mechanical stability of the pedicle screw. Here, we sought to investigate the biomechanical and histological properties of stabilization of expandable pedicle screw (EPS) in the osteoporotic spine in sheep. EPSs and standard pedicle screws, SINO screws, were inserted on the vertebral bodies in four female ovariectomized sheep. Pull-out and cyclic bending resistance test were performed to compare the holding strength of these pedicle screws. High-resolution micro-computed tomography (CT) was performed for three dimensional image reconstruction. We found that the EPSs provided a 59.6% increase in the pull-out strength over the SINO screws. Moreover, the EPSs withstood a greater number of cycles or load with less displacement before loosening. Micro-CT image reconstruction showed that the tissue mineral density, bone volume fraction, bone surface/bone volume ratio, trabecular thickness, and trabecular separation were significantly better in the expandable portion of the EPSs than those in the anterior portion of the SINO screws (P < 0.05). Furthermore, the trabecular architecture in the screw-bone interface was denser in the expandable portion of the EPS than that in the anterior portion of the SINO screw. Histologically, newly formed bone tissues grew into the center of EPS and were in close contact with the EPS. Our results show that the EPS demonstrates improved biomechanical and histological properties over the standard screw in the osteoporotic spine. The EPS may be of value in treating patients with osteoporosis and warrants further clinical studies. PMID- 20577768 TI - Balancing resource constraints against quality of care. PMID- 20577769 TI - Surgical mammography reporting in a limited resource environment. AB - BACKGROUND: Lack of resources and dedicated breast radiology has forced professionals other than radiologists to read mammography. We report a series of surgeon-read mammography in a developing country. METHODS: Data were collected prospectively form January 2003 to June 2008 for all mammography performed at a tertiary hospital. The data acquired were demographics, previous treatment for breast pathology, and indication for and outcome of mammography, including diagnostic procedures and their results. The results were benchmarked against standard performance indicators. RESULTS: Of 8,743 mammograms performed, 1,468 were for palpable lumps; the cancer diagnosis rate was 640 per 1,000 investigations (for 885 of these reported as compatible with malignancy, the cancer diagnosis rate was 95%; for 183 reported as indeterminate 60%, for 400 reported as benign/no abnormality 4%). Of 4,998 cancer follow-up mammograms, the cancer diagnosis rate was 15 per 1,000. For 76 of these reported as compatible with malignancy, the cancer diagnosis rate was 67%, for 161 reported as indeterminate, the biopsy rate was 36%, and cancer diagnosis rates of biopsy was 41%. Of 75 cancers diagnosed, 26 were locally recurrent after breast conservation and 49 new contralateral primaries, 84% of these were stage 0-I. Of 2,001 mammograms performed for screening, the biopsy rate was 4.5% and the cancer diagnosis rate of biopsy was 27%; the overall cancer diagnosis rate was 11 per 1,000 examinations; 96% of these were stage 0-1. CONCLUSIONS: Dedicated breast surgeons are equally proficient at mammography interpretation as radiologists. In resource-restricted environments, nonavailability of dedicated breast radiologists should not preclude development of breast units. PMID- 20577770 TI - Pathobiological characterization of low-pathogenicity H5 avian influenza viruses of diverse origins in chickens, ducks and turkeys. AB - We undertook one of the most comprehensive studies on the replication and intraspecies transmission characteristics of low-pathogenicity avian influenza viruses in ducks, chickens and turkeys. Our results indicated that most of these isolates could replicate and be transmitted in poultry without inducing clinical disease. However, differences in transmission to contact control birds were noted, emphasizing the importance of having contact control cage mates in biological characterization experiments. Ducks supported the replication of viruses of wild aquatic bird origin in their respiratory and digestive tracts equally well. The viruses from wild aquatic birds were not effectively transmitted among chickens. In contrast, the wild-bird isolates and viruses of domestic bird origin from live-bird markets and commercial poultry operations replicated and were transmitted more efficiently in turkeys than in chickens or ducks. We also found a lower minimal infectious dose requirement for infection of turkeys compared to chickens and ducks. Our data support an important role of turkeys as being more susceptible hosts for avian influenza viruses than domestic ducks and chickens. These results highlight the role of turkeys as intermediate or bridging hosts in the transmission of influenza viruses from wild birds to land-based domestic poultry or among different land-based bird species. PMID- 20577771 TI - Stress-mediated alteration in V-ATPase and V-PPase of Butea monosperma. AB - The activity and subunit amounts of V-ATPase and V-PPase in various plants of Butea monosperma Taub. (Fabaceae) (ver. Dhak; Palas) growing as a natural inhabitant in varying stress conditions in southeast Rajasthan were studied. Western blot analysis followed by immunological quantification of V-ATPase subunits using specific polyclonal antibodies showed that the subunits A, B, D, E, and c are clearly detectable in all plants, with A, B, and c appearing as intense bands. The other subunits of V-ATPase, viz., C, a, and d, were also detected in majority of the plants. Various subunits exhibited variations in their protein amount in different plants. Besides, a few other clear bands were also detected. Of these, the 30- and 29-kD bands may possibly be Di and Ei. Furthermore, a clear band of V-PPase corresponding to 67-70 kD was also detected. A comparison of the V-ATPase and V-PPase activity revealed that Butea plants in the upper region of the study site showed 70% and 39% higher activity, respectively. Furthermore, the immunological quantification showed that the V ATPase and V-PPase protein amounts are also higher in the upper Butea plants which have drought stress and, moreover, are also exposed to stronger light intensities for relatively longer duration. PMID- 20577772 TI - Amaurosis, ophthalmoplegia, ptosis, mydriasis and periorbital blanching following inferior alveolar nerve anaesthesia. AB - BACKGROUND: Ophthalmic complications following inferior alveolar nerve anaesthesia are rare. They include transient blindness (amaurosis), ophthalmoplegia, ptosis, mydriasis and diplopia. These events may occur following the intravascular administration of anaesthetic solution and are distressing to both patient and operator alike. CASE REPORT: We report the unusual case of a young patient who experienced amaurosis, total ophthalmoplegia, complete upper eyelid ptosis, mydriasis and periorbital blanching following inferior alveolar nerve anaesthesia. Similar but less profound signs were observed in the same patient on a subsequent occasion. This was following general anaesthesia, during which she had received local anaesthetic prior to mandibular wisdom tooth removal. CONCLUSIONS: Ophthalmic complications following inferior alveolar nerve anaesthesia are rare but distressing events. In particular, amaurosis is an extremely rare event and usually heralds a more sinister pathology such as stroke. Clinicians should be aware of these complications to minimise anxiety and reassure their patients appropriately. PMID- 20577773 TI - Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease. AB - The prevalence of Clostridium difficile infection (CDI) in pediatric patients with inflammatory bowel disease (IBD) is still not sufficiently recognized. We assessed the prevalence of CDI and recurrences in outpatients with IBD. In addition, the influence of IBD therapy on CDI and antimicrobial susceptibility of the potentially causative C. difficile strains was assessed. This was a prospective, single-center, observational study. All specimens were obtained between January 2005 and January 2007 from the IBD outpatient service and screened for C. difficile and its toxins. C. difficile isolates were genotyped by PCR ribotyping. Diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was based on Porto criteria. Severity of disease was assessed using the Hyams scale (for Crohn's disease) and the Truelove-Witts scale (for ulcerative colitis). One hundred and forty-three fecal samples from 58 pediatric IBD patients (21 with Crohn's disease and 37 with ulcerative colitis) were screened. The risk of C. difficile infection was 60% and was independent of disease type (CD or UC) (chi2 = 2.5821, df = 3, p = 0.4606). About 17% of pediatric IBD patients experienced a recurrence of CDI. All C. difficile strains were susceptible to metronidazole, vancomycin and rifampin. A high prevalence of C. difficile infection and recurrences in pediatric outpatients with IBD was observed, independent of disease type. There was no significant correlation between C. difficile infection and IBD therapy. PCR ribotyping revealed C. difficile re-infection and relapses during episodes of IBD in pediatric outpatients. PMID- 20577774 TI - Comparison of short-pulsed and long-pulsed 532 nm lasers in the removal of freckles. AB - The purpose of this study was to compare the efficacy and safety of the 532 nm long-pulsed laser (10 ms) with that of the 532 nm short-pulsed laser (10 ns) for freckle removal. Currently, the gold standard for treatment is the short-pulsed laser. Recently, several long-pulsed lasers have been introduced for both hair removal and the treatment of freckles. To our investigative team's knowledge, no controlled experiments have been performed to compare the safety and efficacy of long-pulsed versus short-pulsed lasers for the treatment of freckles. This was a 4-week trial, and all patients had three freckles that were randomly allocated to be treated with short-pulse laser, long-pulse laser, or to receive no treatment (control). All patients had three freckles that were randomly selected to be treated with short-pulse 532 nm Medlite IV laser (10 n, 1 J/cm(2)), or long-pulse 532 nm Aura laser (10 ms, 1 J/cm(2)) or to remain as a control (no treatment). The laser treatment was only performed once, followed by a 1-day and a 1-month follow-up visit. Freckle size was determined by a novel surface area measurement technique that was created by our research staff. The study included 17 sets of freckles (three in each set). All of the lesions which received the short-pulsed laser treatment had immediate whitening of the lesions, which turned into dry scabs the next day. None of the freckles treated in the long-pulsed group or control group developed immediate whitening or scabs. No blisters or ulcers developed. The average pain score in the short-pulsed laser group was 2-3 out of 10, while it was 0 out of 10 in the long-pulsed laser group. All scabs that developed in the short-pulsed laser group fell off between days 6 and 12 (average 8 days). The outcome of this study verified the appropriate treatment of freckles. The study confirmed that when the same energy settings, short-pulsed laser is the more effective laser treatment regimen (when compared with the long pulsed laser), with high tolerability and minimal side effects for patients with skin types I to IV. PMID- 20577775 TI - Drift and diffusion of a confined semiflexible chain. AB - We study the transverse and longitudinal linear response function of rigid chains subjected to an external force. Our main concern are stiff polymers confined in narrow pores with diameter less than their persistence length. We explicitly consider confinement in a transverse harmonic potential and generalize results by scaling arguments. Our results describe the drift of the filament under an external force, time evolution of the filament shape, and filament diffusion. Diffusion of a confined filament resembles the celebrated reptation process for flexible chains, albeit with distinct kinetic exponents. The limiting case of stiff free filaments is also mentioned. PMID- 20577776 TI - Mitochondrial dynamics in cell death and neurodegeneration. AB - Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Abeta peptide and mutant huntingtin protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson's disease-related genes also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. PMID- 20577777 TI - Pax6 localizes to chromatin-rich territories and displays a slow nuclear mobility altered by disease mutations. AB - The transcription factor Pax6 is crucial for the embryogenesis of multiple organs, including the eyes, parts of the brain and the pancreas. Mutations in one allele of PAX6 lead to eye diseases including Peter's anomaly and aniridia. Here, we use fluorescence recovery after photobleaching to show that Pax6 and also other Pax family proteins display a strikingly low nuclear mobility compared to other transcriptional regulators. For Pax6, the slow mobility is largely due to the presence of two DNA-binding domains, but protein-protein interactions also contribute. Consistently, the subnuclear localization of Pax6 suggests that it interacts preferentially with chromatin-rich territories. Some aniridia-causing missense mutations in Pax6 have impaired DNA-binding affinity. Interestingly, when these mutants were analyzed by FRAP, they displayed a pronounced increased mobility compared to wild-type Pax6. Hence, our results support the conclusion that disease mutations result in proteins with impaired function because of altered DNA- and protein-interaction capabilities. PMID- 20577778 TI - An oxygen-consuming phantom simulating perfused tissue to explore oxygen dynamics and (19)F MRI oximetry. AB - OBJECTIVE: This study presents a reproducible phantom which mimics oxygen consuming tissue and can be used for the validation of (19)F MRI oximetry. MATERIALS AND METHODS: The phantom consists of a haemodialysis filter of which the outer compartment is filled with a gelatin matrix containing viable yeast cells. Perfluorocarbon emulsions can be added to the gelatin matrix to simulate sequestered perfluorocarbons. A blood-substituting perfluorocarbon fluid is pumped through the lumen of the fibres in the filter. (19)F relaxometry MRI is performed with a fast 2D Look-Locker imaging sequence on a clinical 3T scanner. RESULTS: Acute and perfusion-related hypoxia were simulated and imaged spatially and temporally using the phantom. CONCLUSIONS: The presented experimental setup can be used to simulate oxygen consumption by somatic cells in vivo and for validating computational biophysical models of hypoxia, as measured with (19)F MRI oximetry. PMID- 20577779 TI - Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors. AB - The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 MUg/10 MUl) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 MUg/MUl/h for 168 h.) beginning at 7 d after tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy * 3) of 6 MV photons to the whole brain beginning on the day after drug administration. Other groups of rats received either carboplatin or X-irradiation alone. The tumor carboplatin concentration following CED of 20 MUg in 10 MUl was 10.4 MUg/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small tumors, treated with carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either oral administration or CED of temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98 glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of carboplatin in patients with recurrent glioblastomas, and ultimately a Phase II trial of carboplatin in combination with radiation therapy. PMID- 20577780 TI - IL-8 is a mediator of NF-kappaB induced invasion by gliomas. AB - Glioblastoma (GBM) is the most common and deadly form of primary brain tumor with a median survival of eleven months, despite use of extensive chemotherapy, radiotherapy and surgery. We have previously shown that nuclear factor-kappa B (NF-kappaB) is aberrantly expressed in GBM tumors and primary cell lines derived from tumor tissue. Here we show that IL-8, a chemokine is also aberrantly expressed by GBM cell lines and expression of IL-8 is in large part, attributable to the aberrant activation of NF-kappaB. We hypothesized that invasiveness of GBM cells is driven at least in part by aberrantly expressed IL-8. In support of the hypothesis we found that treatment of glioma cells with an IL-8 neutralizing antibody markedly decreased their invasiveness compared to cells treated with control IgG or left untreated. Furthermore, downregulation of IL-8 protein production with use of IL-8 targeted siRNA also resulted in decreased invasion in matrigel. We next investigated the presence of IL-8 receptors by FACS analysis and found that GBM cells (U87, U251, D54 and LN229) only express CXCR1 but not CXCR2. Treatment of U87 cells with a blocking CXCR1 antibody reduced their invasion through matrigel. Finally, we found that addition of exogenous IL-8, following downregulation of NF-kappaB which results in loss of endogenous IL-8 production, incompletely restored tumor cell invasion. Our data indicate that IL 8 is necessary but not solely responsible for glioma cell invasion and mediates its effect in an autocrine manner. PMID- 20577781 TI - Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation. AB - Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis. PMID- 20577782 TI - Genome-wide transcriptome analysis of the adaptive response of Enterococcus faecalis to copper exposure. AB - In this work we investigated the adaptive response of E. faecalis to Cu and the role of CopY, a Cu-dependent repressor, in the regulation of Cu metabolism. In doing so, we examined the whole-genome transcriptional response of E. faecalis wild-type (WT) and a DeltacopY strain exposed to non-toxic Cu excess. The results indicated that after Cu exposure, most of the genes that displayed a significant change in their expression levels in the WT strain (135 of the 145 up-regulated genes and 115 of the 142 down-regulated genes) were also differentially expressed in the E. faecalis DeltacopY strain. This extensive overlap in the transcriptional response, suggested that additional transcription factors mediate the response of E. faecalis to Cu. As a first step to analyze this possibility, we selected among the up-regulated genes five genes encoding putative transcriptional regulators and determined their expression levels at different times after Cu exposure. The temporal expression of these regulators was different from that of copY, which reached its maximum at the earliest time measured. Nevertheless, transcription elongation factor GreA, and members of Rrf2, Cro/CI and SorC/DeoR transcription factor families were induced shortly after Cu exposure, suggesting that these proteins are able to complement the role of CopY in the regulatory network activated by Cu. To our knowledge, this is the first report on the global transcriptional response to Cu in a member of this taxonomic group. PMID- 20577783 TI - From GC-rich DNA binding to the repression of survivin gene for quercetin nickel (II) complex: implications for cancer therapy. AB - The DNA binding and cleavage properties of quercetin nickel (II) complex have been studied, but little attention has been devoted to the relationship between antitumor activity of this complex and DNA-binding properties. In the present study, we report that quercetin nickel (II) complex showed significant cytotoxicity against three tumor cell lines (HepG2, SMMC7721 and A549). Hoechst33258 and AO/EB staining showed HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to quercetin nickel (II) complex. We also demonstrate that the levels of survivin and bcl-2 protein expression in HepG2 cells decreased concurrently, and the levels of p53 protein increased significantly after treatment with quercetin nickel (II) complex by immunocytochemistry analysis. The relative activity of caspase-3 and caspase-9 increased significantly after treatment with the complex. Furthermore, fluorescence measurements and molecular modeling were performed to learn that the complex could be preferentially bound to DNA in GC region. These results imply that quercetin nickel (II) complex may intercalate into the GC-rich core promoter region of survivin, down-regulating survivin gene expression and promoting tumor cells apoptosis. So our results suggest that antitumor activity of quercetin nickel (II) complex might be related to its intercalation into DNA and DNA binding selectivity, and that the complex may be a promising agent for cancer therapy. PMID- 20577784 TI - Groundwater contaminations and health perspectives in developing world case study: Gaza Strip. AB - Groundwater is the only source of water in the Gaza Strip. The results of a 10 year monitoring program revealed that more than 90% of the available water is not suitable for drinking purposes as a result of elevated chemical contaminants as well as microbiological organisms. The archives of the local hospitals showed catastrophic records on diseases caused by water directly and indirectly. Methemoglobinemia and dental fluorosis are well-known diseases caused by elevated nitrate and fluoride, respectively. Water-borne diseases are currently high and will increase if water, sanitation, and food-control services are not restored, or are allowed to deteriorate further. Heavy use and misuse of banned and prohibited pesticides may show other hard diseases in the near future. Geography, politics, and war combine to make the Gaza Strip a worst-case scenario for water resource planners. Urgent alternative water resources should be secured and the human health should be given the highest priority. PMID- 20577785 TI - Dual growth factor-releasing nanoparticle/hydrogel system for cartilage tissue engineering. AB - In order to induce the chondrogenesis of mesenchymal stem cells (MSCs) in tissue engineering, a variety of growth factors have been adapted and encouraging results have been demonstrated. In this study, we developed a delivery system for dual growth factors using a gelation rate controllable alginate solution (containing BMP-7) and polyion complex nanoparticles (containing TGF-beta(2)) to be applied for the chondrogenesis of MSCs. The dual growth factors (BMP-7/TGF beta(2))-loaded nanoparticle/hydrogel system showed a controlled release of both growth factors: a faster release of BMP-7 and a slower release of TGF-beta(2), ca., approximately 80 and 30% release at the end of an incubation period (21 days), respectively, which may be highly desirable for chondrogenic differentiation of MSCs. On the contrary, the release of each growth factor from the dual growth factors-loaded hydrogel (without the nanoparticles) was much slower than that of the nanoparticle/hydrogel system, approximately 36% (BMP-7) and 16% (TGF-beta(2)) for 21 days, and this is more than likely attributed to the aggregation between growth factors during the hydrogel fabrication step. The nanoparticle/hydrogel system with separate growth factor loading may provide desirable growth factor delivery kinetics for cartilage regeneration, as well as the chondrogenesis of MSCs. PMID- 20577786 TI - Bisethylnorspermine lipopolyamine as potential delivery vector for combination drug/gene anticancer therapies. AB - PURPOSE: To design novel synthetic gene delivery system in which the carrier molecule functions dually as a carrier and a cytotoxic agent targeting dysregulated polyamine metabolism in cancer. METHODS: Bisethylnorspermine (BENSpm) lipopolyamine was synthesized and its toxicity evaluated by MTS assay in MCF-7 and MCF-10A cells. Transfection activity was determined using luciferase plasmid DNA. RESULTS: Asymmetrical lipid analogue of polyamine anticancer drug BENSpm was synthesized using nucleophilic ring opening of azetidinium ion. The synthesized LipoBENSpm showed cytotoxicity comparable to that of parent BENSpm in human breast cancer cell line MCF-7 but mediated 3-4 orders magnitude higher transfection activity. Importantly, cytostatic activity of BENSpm, typically in a low muM range, falls within a relevant and typical concentration range required for efficient gene delivery. CONCLUSIONS: These findings make gene delivery vectors based on BENSpm promising candidates for combination drug/gene approaches to the treatment of cancer. PMID- 20577789 TI - Lottery promotions at the point-of-sale in Ontario, Canada. AB - We documented the extent of point-of-sale (POS) lottery promotions in Ontario, Canada and the relationship between lottery promotions and store and city characteristics. This is the first quantitative study of POS lottery promotions. A total of 366 stores-independent and chain convenience stores, gas stations and grocery stores-were visited across 20 cities in Ontario. Data collectors unobtrusively observed the type of lottery promotions in each store and completed a data collection checklist. A lottery promotion index was created and hierarchical linear modeling (HLM) was conducted to examine the relationship between extent of lottery promotions and independent variables such as neighbourhood socioeconomic status and city prevalence of lottery ticket purchasing. POS lottery promotions were widespread across Ontario, with the highest level of promotion found in independent convenience stores. In the multivariable HLM model, none of the remaining independent variables remained statistically significant, except for store type. Lottery promotions are extensive at the POS in Ontario. These findings can help initiate discussions around the appropriateness and possible future regulation of this form of advertising. PMID- 20577787 TI - Vehicle composition influence on the microneedle-enhanced transdermal flux of naltrexone hydrochloride. AB - PURPOSE: Transdermal delivery of drugs is often limited by formidable barrier properties of stratum corneum (SC). Microneedles (MN) enable creation of transient microchannels in the SC and bypass this barrier. Many reports have focused on the great effectiveness of MN in improving percutaneous flux values of a variety of drugs over a large molecular size spectrum. The objective of the present study is to evaluate the influence of formulation on MN-enhanced transdermal transport of naltrexone hydrochloride (NTX HCl). METHODS: A series of in vitro experiments employing binary mixtures of propylene glycol (PG) and water as vehicle were used with either MN-treated or untreated skin. A simple model taking into account two parallel flux values through intact skin and microchannels was used to analyze data. RESULTS: Transdermal permeation of NTX HCl from different donor solutions indicated that PG-rich formulations greatly limited MN-enhanced transport but had a much smaller effect on transport through intact skin. CONCLUSIONS: Diffusion through the microchannel pathway seems to be donor viscosity-related and follows the relationship predicted by the Stokes Einstein equation as shown by linear dependence of flux on diffusivity of NTX in donor solutions. PMID- 20577791 TI - Plasma levels of C-telopeptide pyridinoline cross-links of type I collagen and osteocalcin in chronic periodontitis. AB - This study was planned to investigate whether chronic periodontitis patients exhibit different plasma concentrations of C-telopeptide pyridinoline cross-links of type I collagen (ICTP) and osteocalcin (OC) compared to the clinically healthy controls. Before initiation of any periodontal intervention, plasma samples and full-mouth clinical periodontal recordings were obtained from 58 otherwise healthy patients with chronic periodontitis and also from 47 systemically and periodontally healthy control subjects. Plasma ICTP levels were determined by radioimmunoassay and OC levels by enzyme-linked immunosorbent assay. Data were tested statistically using t test and ANOVA. The healthy control group exhibited significantly lower values in all clinical periodontal measurements (P < 0.001). There were no significant differences between the study groups in plasma ICTP and OC levels (P > 0.05). Within the limits of this study, it may be suggested that plasma levels of ICTP and OC may not provide distinguishing data between chronic periodontitis patients and clinically healthy subjects. PMID- 20577790 TI - An exploratory study of clinical measures associated with subsyndromal pathological gambling in patients with binge eating disorder. AB - Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems. PMID- 20577792 TI - An observational registry on efficacy and safety of the right ventricular outflow tract as a site for ICD leads: results of the EFFORT (EFFicacy Of Right ventricular outflow Tract as site for ICD leads) registry. AB - BACKGROUND: Although pacing from the right ventricular outflow tract (RVOT) has been shown to be safe and feasible in terms of sensing and pacing thresholds, its use as a site for implantable cardioverter defibrillator (ICD) leads is not common. This is probably due to physicians' concerns about defibrillation efficacy. To date, only one randomized trial, involving 87 enrolled patients, has evaluated this issue. OBJECTIVE: The aim of this observational study has been to compare safety (primary combined end point: efficacy of a 14-J shock in restoring sinus rhythm, R wave amplitude >4 mV and pacing threshold <1 V at 0.5 ms) and efficacy (in terms of effectiveness of a 14-J shock in restoring sinus rhythm after induction of VF, secondary end point) of two different sites for ICD lead positioning: RVOT and right ventricular apex (RVA). METHODS: The study involved 185 patients (153 males; aged 67 +/- 10 years; range, 28-82 years). Site of implant was left to physician's decision. After implant, VF was induced with a 1 J shock over the T wave or--if this method was ineffective--with a 50-Hz burst, and a 14-J shock was tested in order to restore sinus rhythm. If this energy was ineffective, a second shock at 21 J was administered and--eventually--a 31-J shock followed--in case of inefficacy--by a 360-J biphasic external DC shock. Sensing and pacing thresholds were recorded in the database at implant, together with acute (within 3 days of implant) dislodgement rate. RESULTS: The combined primary end point was reached in 57 patients in the RVOT group (0.70%) and in 81 patients in the RVA group (0.79%). The 14-J shock was effective in 159 patients, 63 in the RVOT group (77%) and 86 in the RVA group (83%). Both the primary and the secondary end points are not statistically different. R wave amplitude was significantly lower in the RVOT group (10.9 +/- 5.2 mV vs. 15.6 +/- 6.4 mV, p < 0.0001), and pacing threshold at 0.5 ms was significantly higher (0.64 +/- 0.25 V vs. 0.52 +/- 0.20 V, p < 0.01), but these differences do not seem to have a clinical meaning, given that the lower values are well above the accepted limits in clinical practice. CONCLUSIONS: Efficacy and safety of ICD lead positioning in RVOT is comparable to RVA. Even if we observed statistically significant differences in sensing and pacing threshold, the clinical meaning of these differences is--in our opinion--irrelevant. PMID- 20577793 TI - Identification of the VP92R gene from infectious spleen and kidney necrosis virus. AB - Megalocytiviruses, which belong to the family Iridoviridae, are among the most harmful viruses to cultured fishes. Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus. The genome of ISKNV was sequenced and annotated by He et al. (Virology 291:126-139, 2001) in 2001 and re annotated by Eaton et al. (Virol. J. 4:11, 2007) in 2007. The ORF092R of ISKNV was identified in the annotations of He et al. but was not reported by Eaton et al. In this study, by using Northern-blot and RACE assays, we identified the ORF092R transcript, indicating that ORF092R was indeed transcribed in the ISKNV infected cells. Immunofluorescence and Western-blot showed that VP92R protein was expressed in the ISKNV-infected cells, and the molecular mass of VP92R is consistent with the theoretical one. Sequence comparison demonstrated that the VP92R orthologous protein is present in large yellow croaker iridovirus (LYCIV), but not in rock bream iridovirus (RBIV) or orange-spotted grouper iridovirus (OSGIV). Therefore, VP92R may have specific functions during ISKNV pathogenesis and could be a subject for studying the differences between megalocytiviruses. PMID- 20577794 TI - A longitudinal investigation of the impact of life stress on HIV treatment adherence. AB - Suboptimal antiretroviral adherence is associated with poorer HIV outcomes. Psychosocial factors, including life stress, depression and coping, may influence adherence behavior. This prospective investigation sought to examine the impact of life stress (acute life events, chronic stress, and perceived stress), depression, and coping style on adherence to HIV treatment regimes over time. Participants were 87 treatment-seeking HIV-infected individuals recruited from an urban HIV clinic. They completed clinician-administered interviews and self report questionnaires at baseline and 3-month follow-up. Acute life events and chronic stress prospectively predicted decreases in treatment adherence more strongly among individuals in a major depressive episode (n = 21) compared to non depressed individuals (n = 66). Coping style did not appear to be the mechanism by which life stress influenced adherence among depressed HIV-infected individuals. These findings demonstrate that life stress has toxic effects for depressed individuals and suggest that treatment adherence interventions with depressed individuals could be enhanced via development of stress management skills. PMID- 20577795 TI - High gamma oscillations of sensorimotor cortex during unilateral movement in the developing brain: a MEG study. AB - Recent studies in adults have found consistent contralateral high gamma activities in the sensorimotor cortex during unilateral finger movement. However, no study has reported on this same phenomenon in children. We hypothesized that contralateral high gamma activities also exist in children during unilateral finger movement. Sixty normal children (6-17 years old) were studied with a 275 channel MEG system combined with synthetic aperture magnetometry (SAM). Sixty participants displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (65-150 Hz) in the primary motor cortices (M1) of both hemispheres. Interestingly, nineteen younger children displayed ipsilateral event-related synchronization (I-ERS) within the high gamma band (65-150 Hz) just during their left finger movement. Both I-ERS and C-ERS were localized in M1. The incidence of I-ERS showed a significant decrease with age. Males had significantly higher odds of having ipsilateral activity compared to females. Noteworthy, high gamma C-ERS appeared consistently, while high gamma I-ERS changed with age. The asymmetrical patterns of neuromagnetic activities in the children's brain might represent the maturational lateralization and/or specialization of motor function. In conclusion, the present results have demonstrated that contralateral high-gamma neuromagnetic activities are potential biomarkers for the accurate localization of the primary motor cortex in children. In addition, the interesting finding of the ipsilateral high-gamma neuromagnetic activities opens a new window for us to understand the developmental changes of the hemispherical functional lateralization in the motor system. PMID- 20577796 TI - Response of algal metrics to nutrients and physical factors and identification of nutrient thresholds in agricultural streams. AB - Many streams within the United States are impaired due to nutrient enrichment, particularly in agricultural settings. The present study examines the response of benthic algal communities in agricultural and minimally disturbed sites from across the western United States to a suite of environmental factors, including nutrients, collected at multiple scales. The first objective was to identify the relative importance of nutrients, habitat and watershed features, and macroinvertebrate trophic structure to explain algal metrics derived from deposition and erosion habitats. The second objective was to determine if thresholds in total nitrogen (TN) and total phosphorus (TP) related to algal metrics could be identified and how these thresholds varied across metrics and habitats. Nutrient concentrations within the agricultural areas were elevated and greater than published threshold values. All algal metrics examined responded to nutrients as hypothesized. Although nutrients typically were the most important variables in explaining the variation in each of the algal metrics, environmental factors operating at multiple scales also were important. Calculated thresholds for TN or TP based on the algal metrics generated from samples collected from erosion and deposition habitats were not significantly different. Little variability in threshold values for each metric for TN and TP was observed. The consistency of the threshold values measured across multiple metrics and habitats suggest that the thresholds identified in this study are ecologically relevant. Additional work to characterize the relationship between algal metrics, physical and chemical features, and nuisance algal growth would be of benefit to the development of nutrient thresholds and criteria. PMID- 20577797 TI - A flounder (Paralichthys olivaceus) gill cell line as in vitro acute assay system of nonylphenol cytotoxicity. AB - A cell line (FG cells) derived from a gill of the flounder, Paralichthys olivaceus were used to determine the cytotoxic effects of nonylphenol (NP). Cytotoxicity was measured by three endpoint systems: neutral red (NR) uptake assay, methyl thiazolyl tetrazolium (MTT) assay and cell protein assay. The result showed that NP was cytotoxic to FG cells at all tested concentrations, and toxicity increased as the concentration of NP was progressively increased. The 24 h-IC50 values of NP were 39.81, 37.76 and 38.22 MUmol/L for NR uptake, MTT assay and cell protein assay, respectively. Moreover, the morphological changes of FG cells were also studied at the concentration of 30 MUmol/L for 24 h. Cells morphology were markedly altered by NP observed under a scanning electron microscopy, as evidenced by swelling cells, two and more nucleolus and an increased number of lipid particles. This would suggest that the FG cell line is a suitable bioindicator for the screening of the acute toxicity of NP. PMID- 20577798 TI - Streamflow variability and hydroclimatic change at the Bear Brook Watershed in Maine (BBWM), USA. AB - Seasonal variations in streamflow and the associated hydrologic extremes impart significant temporal structure to watershed-scale chemical fluxes. Consequently, a careful characterization of the episodic-to-seasonal and longer-term streamflow variations is a first step toward developing a comprehensive view of the temporal dynamics of watershed processes in a changing climate. Here we analyze a nearly two-decade-long streamflow record for the East Bear subwatershed within the Bear Brook Watershed in Maine (BBWM) (USA) to understand the envelope of streamflow variability by season, with a particular focus on the high flow events that have a disproportionately large impact on the biogeochemical processes and fluxes. Interannual and longer-term variations in a number of derived statistical metrics of hydrologic variability are examined. Our analysis shows substantial interannual and longer-term variability in seasonal flow volumes and peak flows. Furthermore, a long, unimpaired streamflow record for the Narraguagus River (a proximate watershed to the BBWM) is examined with a view to understand the relative coherence in hydrologic variability, as well as quantifying the decadal and longer-term hydrologic variations in this region. We find that the streamflow variability in the two watersheds shows similarity in all seasons. A moving window analysis to assess the changing flood potential over time indicates upward trends in the recent decades. Spring season (March-May) flood estimates show a near-monotonic trend over the 1949-2008 record. Finally, empirical relationships between streamflow and large-scale atmospheric circulation patterns highlight the regional and global climatic drivers of hydrologic extremes in this region, including impacts from remnants of Atlantic hurricanes. PMID- 20577799 TI - Proteomic studies on the development of the central nervous system and beyond. AB - Neuroproteomics has become a 'symbol' or even a 'sign' for neuroscientists in the post-genomic era. During the last several decades, a number of proteomic approaches have been used widely to decipher the complexity of the brain, including the study of embryonic stages of human or non-human animal brain development. The use of proteomic techniques has allowed for great scientific advancements, including the quantitative analysis of proteomic data using 2D DIGE, ICAT and iTRAQ. In addition, proteomic studies of the brain have expanded into fields such as subproteomics, synaptoproteomics, neural plasma membrane proteomics and even mitochondrial proteomics. The rapid progress that has been made in this field will not only increase the knowledge based on the neuroproteomics of the developing brain but also help to increase the understanding of human neurological diseases. This paper will focus on proteomic studies in the central nervous system and especially those conducted on the development of the brain in order to summarize the advances in this rapidly developing field. PMID- 20577800 TI - Effects of hypoxia, glucose deprivation and recovery on the expression of nucleoside transporters and adenosine uptake in primary culture of rat cortical astrocytes. AB - The aim of this study was to explore effects of hypoxia, glucose deprivation (HGD) and recovery on expression and activities of equilibrative nucleoside transporters (rENT) and concentrative nucleoside transporters (rCNT) in rat astrocytes in primary culture. Amounts of cellular ATP in the control group (CG, 5% CO(2) in air, medium containing 7 mM D-glucose, 1 mM Na(+)-pyruvate, 1 h), HGD group (2% O(2)/5% CO(2) in N(2), pyruvate-free medium containing 1.5 mM D-glucose and 10 mM 2-deoxy-D-glucose, 1 h) and recovery group (RG, HGD for 1 h, followed by 1 h exposure to the same conditions as the CG) were (nmol/mg protein, n = 4) 18 +/- 1.6, 4.9 +/- 0.6 and 10.1 +/- 0.8, respectively. Extracellular adenosine concentrations increased from (nM, n = 3) 42 +/- 4 in the CG, to 99 +/- 8 in the HGD group and 86 +/- 3 in the RG. Real-time PCR and immunoblotting revealed that in the HGD group and RG, the amounts of rENT1 mRNA and protein were reduced to 40 and 50%, when compared to the CG, respectively. Astrocyte cultures took up [(3)H]adenosine by concentrative and equilibrative transport processes; however, rENT1-mediated uptake was absent in the RG and cultures from the RG took up significantly less [(3)H]adenosine by equilibrative mechanisms than cultures from the CG. PMID- 20577801 TI - Continuous oxidative stress due to activation of polyamine catabolism accelerates aging and protects against hepatotoxic insults. AB - Enhanced polyamine catabolism via polyamine acetylation-oxidation elevates the oxidative stress in an organism due to increased production of reactive oxygen species (ROS). We studied a transgenic mouse line overexpressing the rate limiting enzyme in the polyamine catabolism, spermidine/spermine N (1) acetyltransferase (SSAT) that is characterized by increased putrescine and decreased spermidine and spermine pools. In order to protect the mice from the chronic oxidative stress produced by the activation of polyamine catabolism, the hepatic expression of the transcription factor p53 was found threefold elevated in the transgenic mice. In addition, the prolonged activation of p53 accelerated the aging of transgenic mice and reduced their lifespan (50%). Aging was associated with decreased antioxidant enzyme activities. In the transgenic mice the activities of catalase and Cu, Zn-superoxide dismutase (SOD) were 42 and 23% reduced respectively, while the expression of CYP450 2E1 was 60% decreased and oxidative stress measured as protein carbonyl content was tenfold elevated. In the transgenic mice, the age-related repression of the different antioxidant enzymes served as a protection against the hepatotoxic effects of carbon tetrachloride and thioacetamide. PMID- 20577802 TI - A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter. AB - We have generated a novel transgenic mouse to direct inducible and reversible transgene expression in the melanocytic compartment. The Dopachrome tautomerase (Dct) control sequences we used are active early in the development of melanocytes and so this system was designed to enable the manipulation of transgene expression during development in utero and in the melanocyte stem cells as well as mature melanocytes. We observed inducible lacZ and GFP reporter transgene activity specifically in melanocytes and melanocyte stem cells in mouse skin. This mouse model will be a useful tool for the pigment cell community to investigate the contribution of candidate genes to normal melanocyte and/or melanoma development in vivo. Deregulated expression of the proto-oncogene MYC has been observed in melanoma, however whether MYC is involved in tumorigenesis in pigment cells has yet to be directly investigated in vivo. We have used our system to over-express MYC in the melanocytic compartment and show for the first time that increased MYC expression can indeed promote melanocytic tumor formation. PMID- 20577803 TI - Bovine trypanosomosis and its vectors in two districts of Bench Maji zone, South Western Ethiopia. AB - A cross-sectional study was carried out from November 2008 to February 2009 in Guraferda and Sheko districts of Bench Maji Zone, South Western Ethiopia. The objective of the study was to determine the prevalence of bovine trypanosomosis and the density of its vectors. An overall prevalence of trypanosome infection in the study area was 4.4%. Trypanosoma congolense (36.36%) was the dominant trypanosome species followed by Trypanosoma vivax (18.18%) and Trypanosoma brucei (9.09%). Mean packed cell volume value of parasitemic animals (21.8%) was significantly (P<0.05) lower than that of aparasitemic animals (27.7%). Biconical and NGU traps were deployed for 72 h, and the result indicated Glossina pallidipes followed by Glossina fuscipes as the only tsetse fly species caught in the study area along with other biting flies like Stomoxys and Tabanus. The apparent density of tsetse flies was 2.83 flies trap(-1) day(-1). NGU trap caught more of G. pallidipes while biconical trap caught more G. fuscipes, and the difference was significant (P<0.05). Although the current study indicated low prevalence of trypanosomosis in the study area, the impacts of trypanosomosis on cattle production and productivity should not be neglected. Therefore, attention should be given to control the disease and also the vector. PMID- 20577804 TI - Study on ectoparasitic defects of processed skins at Sheba Tannery, Tigray, Northern Ethiopia. AB - Study on ectoparasitic skin defects and their impact on the tanning industry was carried out from November 2008 to March 2009. The objectives of the study were to identify the type of skin defects due to ectoparasitic skin diseases that caused downgrading and rejection of pickled sheep and wet blue goat skins at Sheba tannery. A cross-sectional study of pickled and wet blue goat skins processed in Sheba tannery was used as subjects of the study. Accordingly, 700 pickled sheep and 700 wet blue goat skins from each stage were randomly examined to identify the type of skin damage in the tannery. Each selected skin was sorted by size and examined for defects in natural light by skin selectors, and defects on each skin were recorded, and skins were graded into seven grades. The study revealed that scratch was the dominant defect with prevalences of 43.86% and 44.84%, respectively. The prevalence of defect observed in wet blue goat skins due to demodectic mange was 7.74%, while in pickled sheep skins, this was 0%. There was a statistically significant difference (P<0.05) in the prevalence of cockle ("ekek") lesions between pickled sheep skin and wet blue goat skin. Although significant association (P<0.05) was observed between cockle and scratch on both skin types, no association (P>0.05) was seen between scratch and scar. PMID- 20577805 TI - Effect of dietary ascorbic acid supplementation level on productivity, mortality, and carcass characteristics of Venda chickens. AB - Two experiments were carried out to determine the effect of dietary ascorbic acid supplementation levels on productivity, carcass characteristics, and mortality of indigenous Venda chickens. The first experiment determined the effect of dietary ascorbic acid supplementation levels on productivity and mortality rate of 175 unsexed Venda chickens between 1 and 6 weeks old. The second experiment determined the effect of dietary ascorbic acid supplementation levels on productivity, carcass characteristics, and mortality rate of 140 female Venda chickens between 8 and 13 weeks old. A completely randomized design was used in both experiments. Supplementation of grower diets with ascorbic acid ranged from 0 to 2,000 mg per kg DM feed in both experiments. Levels of ascorbic acid supplementation for optimum feed intake, feed conversion ratio, growth rate, live weight, and breast meat yield were determined using a quadratic equation. The optimal dietary ascorbic acid supplementation levels for feed conversion ratio, growth rate, and live weight of Venda chickens during the starter phase were 1,050, 1,301, and 1,500 mg/kg DM feed, while, at the grower phase, the optimal supplementation levels for feed conversion ratio, growth rate, live weight, and breast meat yield were 1,000, 1,250, 1,482, and 769 mg/kg DM feed, respectively. Results indicate that different levels of ascorbic acid supplementation optimized feed conversion ratio, growth rate, and live weight of Venda chickens at each growth phase. However, levels of ascorbic acid supplementation for optimum feed conversion ratio, growth rate, and live weight were higher than that for breast meat yield. These findings have implications on ration formulation for Venda chickens. PMID- 20577806 TI - Feed intake and production parameters of lactating crossbred cows fed maize-based diets of stover, silage or quality protein silage. AB - Thirty-six Boran * Friesian dairy cows (392 +/- 12 kg; mean +/- SD) in early parity were used in a randomised complete block design. Cows were blocked by parity into three blocks of 12 animals and offered normal maize (NM) stover (T1), NM silage (T2) or quality protein maize (QPM) silage (T3) basal diets supplemented with a similar concentrate mix. Feed intake, body weight and condition changes and milk yield and composition were assessed. The daily intake of DM, OM, NDF and ADF for cows fed the NM stover-based diet was higher (P<0.05) than for the cows fed the NM silage and QPM silage-based diets. However, the daily intake of DOM (9.3 kg) and ME (140.8 MJ) for cows on QPM silage-based diet was higher (P<0.05) than for cows on NM stover-based diet (8.4 kg and 124.2 MJ) and NM silage-based diet (7.9 kg and 119.1 MJ). Body weight of cows was affected (P<0.05) by the diet, but diet had no effect (P>0.05) on body condition score, milk yield and milk composition. The digestible organic matter in the NM stover based diet (724 g/kg DM) was lower (P<0.05) than that in the NM (770 g/kg DM) and QPM silage-based diet (762 g/kg DM). It was concluded that the performances of the cows on the NM silage and QPM silage diets were similar and were not superior to that of the NM stover-based diet. PMID- 20577807 TI - Calf health and management in smallholder dairy farms in Tanzania. AB - Smallholder farmers' knowledge and practice of dairy calf management on 129 farms with calves less than 10 months of age in Southeastern and Southern Highland areas of Tanzania was assessed. The method of study included both a farm visit and completion of a questionnaire. Most of the farmers were female, with a primary level of education, and majority kept 1-3 milking cows that yielded 6-10 l milk/cow/day. Most of the calves were fed milk using a residual calf suckling system. Weaning age was 3-8 months. Overall, the body condition of the calves was poor, ranged from 1 to 2.5 with a mode of 2. The majority of the farmers believed that helminthosis was the most common disease condition affecting the calves; diarrhea was ranked as the second. Calf death was reported by 20% of the farmers to have occurred in their herd lasting the 2 years prior to the study. Calf body condition score was related to body weight for calves younger than 9 weeks, and older than 23 weeks of age, whereas no such relationship existed in the age group 9 to 23 weeks. The sex distribution was skewed with less male calves being older than 23 weeks. We hypothesize that male calves experience inferior management compared with female calves. This study demonstrates a low level of knowledge on, and poor practices of calf management among the surveyed farmers that suggest the need for educational intervention. PMID- 20577808 TI - Bd oxidase homologue of photosynthetic purple sulfur bacterium Allochromatium vinosum is co-transcribed with a nitrogen fixation related gene. AB - Purple sulfur bacteria, which are known to be the most ancient among anoxygenic phototrophs, play an important role in the global sulfur cycle. Allochromatium vinosum oxidizes reduced sulfur compounds such as hydrogen sulfide, elemental sulfur and thiosulfide. At low oxygen concentrations, A. vinosum can grow chemotrophically using oxygen as the terminal electron acceptor. Being also a nitrogen fixer, A. vinosum is faced with the paradox of co-existence of aerobic metabolism and nitrogen fixation. Due to growth difficulties, only a few studies have dealt with the aerobic metabolism of the organism and, until now, there has been no information about the genes involved in the respiratory metabolism of purple sulfur bacteria. In this article we show the first terminal oxidase gene for A. vinosum. The presence of a Bd type of quinol oxidase is necessary to protect nitrogenases against the inhibitory effects of oxygen. In this case, a nitrogen fixation related gene is part of the cyd operon and this gene is co transcribed with cydAB genes. Bd oxidase of A. vinosum may be the earliest form of oxidase where the function of the enzyme is to scavenge the contaminant oxygen during nitrogen fixation. This may be an important clue about the early evolution of oxygenic photosynthesis, perhaps as a protective mechanism for nitrogen fixation. PMID- 20577809 TI - Factors associated with attributions about child health conditions and social distance preference. AB - In order to better understand factors that account for the emergence and persistence of negative attitudes towards mental health problems, attributions about and stigma towards children's mental and physical illnesses were examined using National Stigma Study-Children data. Parent blame attributions were most strongly associated with attention deficit disorder, environmental causes with depression, and biology with asthma. Parent blame was more frequent for mental than physical health conditions. Child blame was associated with higher preferred social distance from the child, but no clear links were observed between social distance and attributions about genetic/biology, environment, or parent blame. Rurality was not significantly associated with attributions or social distance preference. Higher educational achievement was associated with increased endorsement of environmental stress factors and reduced odds of child blaming. The general public holds complex explanatory models of and nuanced responses to children's mental disorders that need further investigation, including effects on parents' and children's help-seeking. PMID- 20577810 TI - Use of HbA(1c) in screening for Cuban-Americans with undiagnosed type 2 diabetes. AB - This study evaluated the use of HbA(1c) as a screening tool for undiagnosed type 2 diabetes (fasting plasma glucose >=7.0 mmol/l) in a sample of Cuban-Americans aged >= 30 years old. Subjects were randomly recruited from Miami-Dade and Broward counties, FL. Fasting plasma glucose was measured by hexokinase enzymatic method. HbA(1c) was measured by the DCA2000 + system using the monoclonal antibody method. HbA(1c) demonstrated a high predictive value in detecting undiagnosed diabetes. The area under the receiver operating characteristics (ROC) curve was 0.87. Also, HbA(1c) had high sensitivity and specificity when using a cut off value of 6.37 (71 and 86%, respectively). Moderate sensitivity and very high specificity were shown with a cut off value of 6.84 (57 and 96%, respectively). HbA(1c) is a reliable alternative to fasting plasma glucose in screening for undiagnosed diabetes in Cuban-Americans. PMID- 20577811 TI - Osteogenic differentiation of marrow stromal cells on random and aligned electrospun poly(L-lactide) nanofibers. AB - The fibrillar structure and sub-micron diameter of electrospun nanofibers can be used to reproduce the morphology and structure of the natural extracellular matrix (ECM). The objective of this work was to investigate the effect of fiber alignment on osteogenic differentiation of bone marrow stromal (BMS) cells. Random and aligned poly(L-lactide) (PLLA) nanofibers were produced by collecting the spun fibers on a stationary plate and a rotating wheel, respectively, as the ground electrode. Morphology and alignment of the BMS cells seeded on the fibers were characterized by SEM. The effect of fiber orientation on osteogenic differentiation of BMS cells was determined by measuring alkaline phosphatase (ALPase) activity, calcium content, and mRNA expression levels of osteogenic markers. There was a strong correlation between the fiber and cell distributions for the random (p=0.16) and aligned (p=0.81) fibers. Percent deviation from ideal randomness (PDIR) values indicated that cells seeded on the random fibers (PDIR=6.5%) were likely to be distributed randomly in all directions while cells seeded on the aligned fibers (PDIR=86%) were highly likely to be aligned with the direction of fibers. BMS cell seeded on random and aligned fibers had similar cell count and ALPase activity with incubation time, but the calcium content on aligned fibers was significantly higher after 21 days compared to that of random fibers (p=0.003). Osteopontin (OP) and osteocalcin (OC) expression levels of BMS cells on fibers increased with incubation time. However, there was no difference between the expression levels of OP and OC on aligned vs. random fibers. The results indicate that BMS cells aligned in the direction of PLLA fibers to form long cell extensions, and fiber orientation affected the extent of mineralization, but it had no effect on cell proliferation or mRNA expression of osteogenic markers. PMID- 20577812 TI - Synergistic induction of apoptosis and caspase-independent autophagic cell death by a combination of nitroxide Tempo and heat shock in human leukemia U937 cells. AB - We have shown that heat stress or a superoxide dismutase mimic nitroxide, Tempo, induces apoptosis, while their combination causes nonapoptotic cell death; however, the underlying mechanism for this switch remains unclear. Here we identified for the first time that 10 mM Tempo present during heating at 44 degrees C for 30 min rapidly induced autophagy in U937 leukemic cells in spite of Bax activation and mitochondrial outer membrane (MOM) permeabilization. This co treatment inhibited the processing of heat-activated procaspases-2, -8, -9 and -3 into active small subunits, leading to the inhibition of caspase-dependent apoptosis, and instead caused the induction of autophagy. The inactivation of caspases, a key event, could result from oxidation of active-site-CysSH of all caspases by a prooxidant oxo-ammonium cation, an intermediate derived Tempo during dismutation of heat-induced superoxide anion. In addition, the co treatment caused mitochondrial calcium overloads, the mitochondrial inner membrane permeabilization, profound mitochondrial dysfunction, and liberation of Beclin 1 from the Bcl-2/Beclin 1 complex, all of which contributed to induction of autophagy. These autophagic cells underwent propidium iodide-positive necrosis in a delayed fashion, leading to the complete proliferative inhibition. Remarkably, ruthenium red and BAPTA, which interfere with mitochondrial calcium uptake, facilitated autophagic necrotic death. Cyclosporin A, which binds to cyclophilin D, had a similar necrotic effect. 3-Methyladenine facilitated the necrosis of autophagic cells. In contrast, 5 mM Tempo-44 degrees C/10 min or 44 degrees C/30 min induced Bax-mediated MOM permeabilization and caspase-dependent apoptosis more potently than Tempo alone. Thus, Tempo is a unique thermosensitizer to synergistically induce apoptosis and autophagic cell death. PMID- 20577814 TI - Patterned PDMS based cell array system: a novel method for fast cell array fabrication. AB - Cell-cell interaction is important in numerous biological processes, including cell growth, cell differentiation and migration. The ability to generate pre determined cell patterns or cell arrays on a study surface is crucial for cell cell interaction studies. In this paper, we developed a method for fast cell array fabrication using laser sintering and the hydrophobicity of PDMS films. This approach can be easily adopted and is cost-effective. Hydrophobic PDMS films were fabricated into polymeric chips containing hundreds of microwells. The films were then transferred onto tissue culture surfaces to separate cells in the formation of cell arrays (Patterned PDMS based cell array system, PCAS). We used NIH/3T3 fibroblast cells to demonstrate the feasibility of PCAS. The success of fast fabrication of patterned cell arrays was obtained using different initial cell seeding densities. We also used poorly adherent PC-12 cells to demonstrate the cell-cell communication. Results showed that the method is very useful for studying topics such as cell-cell interaction, cell-substrate interaction or cell migration. PMID- 20577813 TI - Non-surgical stem cell delivery strategies and in vivo cell tracking to injured myocardium. AB - Heart failure is a major economic and public health problem. Despite the recent advances in drug therapy and coronary revascularization, the lost cardiomyocytes due to necrosis and apoptosis are not replaced by new myocardial tissue. Cell therapy is an interesting therapeutic option as it potentially improves contractility and restores regional ventricular function. Early clinical data demonstrated that cell transplantation, mainly delivered through non-surgical methods, is safe and feasible. However, several important issues need to be elucidated. This includes, next to determining the best cell type, the optimal delivery strategy, the biodistribution and the survival of implanted stem cells after transplantation. In this view, pre-clinical animal experiments are indispensable. Reporter genes, magnetic or radioactive labeling of stem cells have been developed to observe the fate and the distribution of transplanted cells using non-invasive imaging techniques. Several studies have demonstrated that these direct and non-direct labeling techniques may become an important tool in cell therapy. Integration of cell delivery and cell tracking will probably be a key for the success of cell therapy in patients. This review will provide a comprehensive overview on the various cell tracking and non-surgical cell delivery techniques, which are highly important in view of experimental and clinical studies. PMID- 20577815 TI - Still unhealthy 2009: building community research to identify risk factors and health outcomes in childhood obesity. AB - The goal of the this study was to track and assess children's health status in Nevada and build relationships between researchers and school districts through the collection of mutually beneficial health data at a local level. All elementary schools in Nevada were sent a health survey for parents of kindergarten students to complete. A total of 3,628 surveys were received with usable height and weight needed to calculate Body Mass Index (BMI). African American and Hispanic children had significantly higher BMI scores compared to Caucasian and Asian/Pacific Islander children, regardless of income. Children who had diabetes or mental health concerns also had significantly higher mean BMIs compared to children without these health concerns. Overall staff within the school districts felt that this surveillance system should be continued as data from this study provided important information subsequently used to guide programming and when applying for grants. Our children's welfare depends on community collaboration to create and implement data-driven initiatives to combat childhood obesity. PMID- 20577816 TI - Overexpression of MTERFD1 or MTERFD3 impairs the completion of mitochondrial DNA replication. AB - The physiological roles of the mitochondrial transcription termination factor (mTERF) family are poorly understood. MTERF and its homologues influence transcriptional readthrough in vitro, but the extent to which they regulate mitochondrial RNA levels in vivo is unclear. In addition, MTERF was previously shown to promote replication pausing. To test their roles in mtDNA metabolism, we created cell-lines inducibly expressing epitope-tagged versions of two members of the mTERF family, MTERFD1 and MTERFD3, as well as shRNA constructs targeted at each. We confirmed mitochondrial targeting and lack of sequence-specific DNA binding for both factors. Over-expression of epitope-tagged MTERFD1 or MTERFD3 resulted in modest mtDNA copy-number depletion and an accumulation of specific mtDNA replication intermediates indicating an impairment of the terminal steps of replication. These findings further implicate the mTERF family in restraining replication fork progression and support the idea that they facilitate the orderly passage of replication and transcription machineries, thus contributing to genome stability. PMID- 20577817 TI - A PCR based SNPs marker for specific characterization of English walnut (Juglans regia L.) cultivars. AB - English walnut (Juglans regia L.) is the most economically important species from all the 21 species belonging to the genus Juglans and is an important and healthy food as well as base material for timber industry. The aim of this study was to develop a simple technique for specific characterization of English walnut using DNA method. The first and second internal transcribed spacers (ITS1 and ITS2) as well as the intervening 5.8S coding region of the rRNA gene for 18 cultivars of J. regia L. isolated from different geographic origins were characterized. The size of the spacers sequences ranged from 257 to 263 bases for ITS1 and from 217 to 219 bases for ITS2. Variation of GC contents has also been observed and scored as 55-56.7 and 57.1-58.9% for ITS1 and ITS2, respectively. This data exhibited the presence of polymorphism among cultivars. Alignment of the ITS1-5.8S-ITS2 sequences from 18 walnut cultivars showed that there were 244 single nucleotide polymorphisms (SNPs) and 1 short insertion-deletion (indel) at 5' end ITS1. Amplification refractory mutation system strategy was successfully applied to the SNP markers of the ITS1 and ITS2 sequences for the fingerprinting analysis of 17 on 18 walnut cultivars. The prediction of ITS1 and ITS2 RNA secondary structure from each cultivar was improved by detecting key functional elements shared by all sequences in the alignments. Phylogenetic analysis of the ITS1-5.8S-ITS2 region clearly separated the isolated sequences into two clusters. The results showed that ITS1 and ITS2 region could be used to discriminate these walnut cultivars. PMID- 20577818 TI - Formation of catalytically active cross-species heterodimers of thymidylate synthase from Plasmodium falciparum and Plasmodium vivax. AB - Thymidylate synthase (TS) of Plasmodium dihydrofolate reductase-thymidylate synthase (DHFR-TS) functions as a homodimeric enzyme with two active sites located near the subunit interface. The dimerization is essential for catalysis, since the active site of each subunit contains amino acid residues contributed from the other TS domain. In P. falciparum DHFR-TS, it has been shown that the active sites require Cys-490 from one domain and Arg-470 donated from the other domain. Mutants of these two series can complement one another giving rise to active enzyme. Here, the potential to form cross-species heterodimers between P. falciparum and P. vivax TS has been explored. Formation of cross-species heterodimer was tested by co-transformation of TS-inactive Cys-490 mutants of P. falciparum or P. vivax with corresponding TS-inactive Arg-486 mutants of P. vivax or P. falciparum into thymidine-requiring Escherichia coli. Active heterodimers were detected by subunit complementation and 6-[(3)H]-FdUMP binding assays. All combinations of the mutants tested, except for (Pf)R470A+(Pv)C506Y, were able to form catalytically active cross-species heterodimers. The single active site formed by (Pf)R470D+(Pv)C506Y and (Pv)R486D+(Pf)C490A pairs of cross-species heterodimers has k(cat) and K(m) values similar to those of intra-species heterodimers of P. falciparum and P. vivax. This is the first report to demonstrate that the TS subunit interface between Plasmodium species is sufficiently conserved to allow formation of fully active cross-species heterodimer. PMID- 20577819 TI - Diseases as natural kinds. AB - In this paper, I focus on life-threatening medical conditions and argue that from the point of view of natural properties, induction(s), and participation in laws, at least some of the ill organisms dealt with in somatic medicine form natural kinds in the same sense in which the kinds in the exact sciences are thought of as natural. By way of comparing two 'divisions of nature', viz., a 'classical' exact science kind (gold) and a kind of disease (Graves disease), I show that there is no justifiable 'ontological gap' between disease kinds and exact sciences kinds. We have instead a difference of degree. PMID- 20577820 TI - Disclosing cancer genetic information within families: perspectives of counselees and their at-risk relatives. AB - PURPOSE: The aim of the present descriptive study was to investigate the experience of sharing genetic information among cancer genetic counselees and their at-risk relatives. METHODS: In total, 147 cancer genetic counselees and 81 of their at-risk relatives answered to a study specific questionnaire and/or were interviewed. Counselees' communication of genetic information to at-risk relatives was assessed with regard to who they informed, how they felt, and how they perceived their relatives' reactions. In addition, at-risk relatives' experiences of receiving genetic information were studied. RESULTS: Most of the counselees had shared the genetic information received at the counseling session personally with their at-risk relatives. The majority of the counselees (68%) reported positive or neutral feelings about sharing the genetic information with their relatives while 9% stated negative feelings. Counselees mostly interpreted the relatives' reactions to the information as positive or neutral (62% of responses), and in few cases as negative (14% of responses). About half of relatives reported positive or neutral reactions (54%) to the received information, while about one-fifth reported negative reactions (22%). Nevertheless, most relatives were satisfied with the received information and half of the relatives intended to seek genetic counseling themselves. CONCLUSION: Sharing genetic information to at-risk relatives appears to be accomplished without any major difficulties or negative feelings. However, more assistance may be needed to optimize the communication of the genetic information within at-risk families. PMID- 20577821 TI - The contribution of breast cancer pathology to statistical models to predict mutation risk in BRCA carriers. AB - BRCA1 and BRCA2 associated breast cancer comprises a small but important group of hereditary breast cancer. Testing for BRCA1 and BRCA2 has significant clinical and personal implications for the patients in terms of therapy and follow-up of individual family members. The sequencing of the genes is expensive and since the information derived may have a profound effect on the individual and family members, it is important that testing is done only when the risk of carrying a mutation is thought to be high. Over the last decade, researchers have developed a number of statistical models for predicting risk for harboring mutations in these genes and the risk of subsequently developing breast and ovarian cancer. These models usually take into account the type of tumor and age at occurrence as well as family history. Data from pathological analysis show that although breast tumours are heterogeneous, there are histological characteristics that are seen more frequently in carriers of BRCA1 germ line mutations compared to BRCA2 and sporadic breast cancers. A number of authors have suggested that the addition of pathological data to risk algorithms may improve the predictive power of these models and provide a more accurate way of identifying individuals who may benefit from testing. Here we review the pathology of familial breast cancer and assess the evidence to justify the use of pathology in refining risk assessment models. PMID- 20577822 TI - Update on DCIS outcomes from the American Society of Breast Surgeons accelerated partial breast irradiation registry trial. AB - BACKGROUND: Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS. MATERIALS AND METHODS: From 2002-2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence. RESULTS: Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%. CONCLUSIONS: During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy. PMID- 20577823 TI - Long-term impact of a structured group-based inpatient-education program for intensive insulin therapy in patients with diabetes mellitus. AB - PURPOSE: Structured patient education aiming to improve self-management strategies might be beneficial for insulin-treated diabetic patients. However, in previous studies the extent of the benefit has been inconsistent in different subgroups of patients. The aim of the present study was to assess the potential benefit of a structured inpatient-education program for intensive insulin therapy according to the basal-bolus concept with particular emphasis on self-management strategies. METHODS: We included 81 diabetic patients (59 with type 1, 14 with type 2, eight with other forms) in this retrospective longitudinal study; all had completed the training program on eight consecutive days at a university clinic between 2003 and 2005. Data assessment included HbA1c, LDL-cholesterol, HDL cholesterol and BMI at baseline (0-15 months before the training) and after 0-5, 5-10 and 10-20 months. RESULTS: A transient decrease of HbA1c (0.2%, 95% CI: 0.04 0.37, P = 0.017) and LDL-cholesterol levels (9.95 mg/dl, 95% CI: 2.24-17.76, P = 0.013) between baseline and the first follow-up examination was observed in the group overall. Thereafter, HbA1c and LDL-cholesterol were similar to baseline, whereas a persistent increase in HDL-cholesterol (P = 0.025) was evident in the multivariable analysis. No changes in BMI were observed. A significant type-by time interaction (P = 0.008) in HbA1c suggests a long-term benefit in glycemic control in patients with type 2 diabetes. CONCLUSION: A diabetes training program for intensive insulin therapy with particular emphasis on self-management skills was followed by a moderate and transient improvement of glycemic control and LDL cholesterol and by a persistent increase in HDL-cholesterol. Long-term improvement in glycemic control was observed only in patients with type 2 diabetes. PMID- 20577824 TI - Coagulation factor VIII levels are associated with long-term survival - interactions with gender in a large hospital-based cohort. AB - INTRODUCTION: Elevated coagulation factor VIII activity has been associated with increased risk for both venous and arterial thrombosis. The current study evaluated the influence of Factor VIII levels and interactions with gender on all cause mortality in a large Austrian cohort. PATIENTS AND METHODS: During 1991 and 2003, 11203 individuals, first ever request for laboratory analyses of FVIII: C, age > or =18 years, were included in this study. The median observation period was 5 years covering a total of 46000 person-years. The death rate was 17.1%. RESULTS: Compared to individuals within the reference category (FVIII: C <94%) hazard ratios gradually increased from 1.4 (95% CI: 1.1-1.8) in the 152-170% category (5th decile) to finally 4.4 (95% CI: 3.5-5.5) in the >313% category (highest decile, all p < 0.05). The association between FVIII: C levels and mortality remained essentially unchanged when considering non-cancer mortality, all cause vascular mortality or mortality due to ischemic heart disease. Compared to males females with elevated FVIII: C had a worse outcome resulting in higher hazard ratios reaching 6.8 (95% CI: 4.6-9.9) within the highest decile compared to males (HR: 3.4 (95% CI: 2.6-4.5)). CONCLUSIONS: In our large patient cohort we might be able to demonstrate for the first time that FVIII: C plasma activity is strongly associated with all cause mortality. Additionally, FVIII: C appears to interact with gender. Especially in women FVIII: C might help identifying high risk cohorts, which might benefit from individualized prevention strategies. PMID- 20577825 TI - Study of the chemical constituents of Pruni Cortex and its related parts. AB - The water extract of Pruni Cortex, which is obtained from the bark of Prunus jamasakura, is a major component in Brocin. We investigated the constituents of the water and methanolic extracts of Pruni Cortex. From the water extractive, two flavonoids (sakuranin and neosakuranin; major constituents of this extractive), four known lignans, and six aromatic compounds including one new compound were obtained. In addition, we also investigated the constituents of the flowers and the leaves of Prunus yedoensis. PMID- 20577826 TI - Study of constituents of Veronicastrum villosulum. AB - We investigated the constituents of Veronicastrum villosulum (Miquel) Yamazaki (Scrophulariaceae), an endangered species belonging to the IA group. From the aerial parts of this plant cultivated at the botanical garden of Sojo University, we isolated two new cucurbitacine-type glycosides, 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 3)]-beta-D-glucopyranosides of 3beta,25 dihydroxycucurbit-5,23(E)-diene-7-one-25-methyl ether and 3beta,23 dihydroxycucurbit-5,24-diene-7-one-23-methyl ether. PMID- 20577827 TI - Overlay visualization in endoscopic ENT surgery. AB - PURPOSE: In endoscopic ENT surgery, the identification and localization of target structures is challenging-depth information is missing, relevant tissues could be hidden behind opaque material and image distortion affects the instrument handling. In this paper, a novel overlay visualization is presented that supports the surgeon by superimposing planning and navigation information on the endoscopic image. METHOD: Target regions, which have been identified in preoperative CT data, are superimposed on the endoscopic image, allowing the use of guiding lines for distance visualization. To match the overlay information with the geometrically distorted endoscopic images, a new intraoperative calibration procedure has been developed. RESULTS: The accuracy of this new method has been verified by cadaver studies. Clinical evaluation in three paranasal sinus interventions was performed to show the intraoperative assistance and practicability with promising results. CONCLUSION: The new techniques safely support the surgeon in locating target structures in the paranasal sinuses with little change in the actual workflow. PMID- 20577828 TI - Binding versus conventional pancreaticojejunostomy after pancreaticoduodenectomy: a case-matched study. AB - BACKGROUND: Postoperative morbidity of pancreaticoduodenectomy remains high and is mainly related to postoperative pancreatic fistula. Peng et al. (J Gastrointest Surg 2003;7:898-900; Am J Surg 2002;183:283-285; Ann Surg 2007;245:692-298) recently described binding pancreaticojejunostomy and reported a zero percent rate of pancreatic fistula. The aim of this study was to compare postoperative outcome of binding pancreaticojejunostomy and conventional pancreaticojejunostomy after pancreaticoduodenectomy. METHODS: Between June 2006 and June 2008, a case-control study was conducted, including all patients with binding pancreaticojejunostomy after pancreaticoduodenectomy. These patients were matched with similar patients with conventional pancreaticojejunostomy. Matching criteria were as follows: age, body mass index, pancreatic texture, and pancreatic main duct size. Postoperative mortality and morbidity were analyzed. Postoperative pancreatic fistula was defined according to the International Study Group of Pancreatic Surgery. RESULTS: Twenty-two patients with binding pancreaticojejunostomy and 25 with conventional pancreaticojejunostomy were included. There was no difference concerning the rate of postoperative pancreatic fistula, but median delay for healing of postoperative pancreatic fistula was longer in the binding pancreaticojejunostomy group (29 vs. 9 days, p = 0.003). Postpancreatectomy hemorrhage was more frequent in the binding pancreaticojejunostomy group (6/22 vs. 0/25, p = 0.023). CONCLUSION: Results of this study showed that binding pancreaticojejunostomy after pancreaticoduodenectomy was not associated with lower postoperative pancreatic fistula and moreover seems to increase postpancreatectomy hemorrhage. PMID- 20577829 TI - Development and characterization of a new epithelial cell line PSF from caudal fin of Green chromide, Etroplus suratensis (Bloch, 1790). AB - A new cell line [pearlspot fin (PSF)] has been developed from caudal fin of Etroplus suratensis, a brackish/freshwater fish cultivated in India. The cell line was maintained in Leibovitz's L-15 supplemented with 10% fetal bovine serum (FBS). The PSF cell line consisted predominantly of epithelial-like cells. The cells were able to grow at temperatures between 25 degrees C and 32 degrees C with optimum temperature of 28 degrees C. The growth rate of PSF cells increased as the FBS proportion increased from 2% to 20% at 28 degrees C with optimum growth at the concentration of 10% FBS. One marine fish virus (fish nodavirus) was tested on this cell line and found not susceptible. After confluency, the cells were subcultured with a split ratio of 1:2. The cells showed epithelial like morphology and reached confluency on the third d after subculture. Polymerase chain reaction amplification of mitochondrial 16S rRNA and COI indicated identity of this cell line with those reported from this fish species, confirming that the cell line was of pearlspot origin. The cells were successfully cryopreserved and revived at the tenth, 25th, and 35th passages. The bacterial extracellular products from Vibrio cholerae MTCC 3904 were found to be toxic to PSF. Karyotyping analysis indicated that the modal chromosome number was 48. PMID- 20577830 TI - Revisional vs. primary Roux-en-Y gastric bypass--a case-matched analysis: less weight loss in revisions. AB - With the increase in bariatric procedures performed, revisional surgery is now required more frequently. Roux-en-Y gastric bypass (RYGB) is considered to be the gold standard revision procedure. However, data comparing revisional vs. primary RYGB is scarce, and no study has compared non-resectional primary and revisional RYGB in a matched control setting. Analysis of 61 revisional RYGB that were matched one to one with 61 primary RYGB was done. Matching criteria were preoperative body mass index, age, gender, comorbidities and choice of technique (laparoscopic vs. open). After matching, the groups did not differ significantly. Previous bariatric procedures were 13 gastric bands, 36 vertical banded gastroplasties, 10 RYGB and two sleeve gastrectomies. The indication for revisional surgery was insufficient weight loss in 55 and reflux in 6. Intraoperative and surgical morbidity was not different, but medical morbidity was significantly higher in revisional procedures (9.8% vs. 0%, p = 0.031). Patients undergoing revisional RYGB lost less weight in the first two postoperative years compared with patients with primary RYGB (1 month, 14.9% vs. 29.7%, p = 0.004; 3 months, 27.4% vs. 51.9%, p = 0.002; 6 months, 39.4 vs. 70.4%, p < 0.001; 12 months, 58.5% vs. 85.9%, p < 0.001; 24 months, 60.7% vs. 90.0%, p = 0.003). Although revisional RYGB is safe and effective, excess weight loss after revisional RYGB is significantly less than following primary RYGB surgery. Weight loss plateaus after 12 months follow-up. PMID- 20577831 TI - New labelling technology for molecular probes applied to the ligation detection reaction-universal array system. AB - The ligation detection reaction (LDR) associated with universal arrays (UA) uses a fluorescently labelled probe (DP) and a Zip Code-extended probe to detect single nucleotide polymorphisms in DNA target sequences. When used for genotyping, the LDR-UA technique uses two DPs, each specific to an allele and labelled with a different fluorophore. The fluorescent signals are processed to calculate the genotype. The uneven decay of fluorophores due to ageing and freezing/thawing cycles and the consequent unequal fluoresce level can lead to erroneous genotype calls. To circumvent this problem, an indirect labelling strategy was developed based on the substitution of the fluorophore with allele specific 22 bp universal labelling sequences (ULS). Labelling is achieved with fluorescently labelled oligos complementary to the ULS (cULS). The strategy improved the uniformity in probe labelling, and generated results comparable to those using direct-labelled probes, as shown by genotyping 22 polymorphic sites in 70 samples with both strategies. This method can be easily implemented in the routine screening with LDR-UA or other techniques. Moreover, the approach results in a significant cost reduction over traditional direct labelling, and offers the possibility to interchange fluorophores and to increase the fluorescent signal by using multiple-labelled cULS. PMID- 20577832 TI - High chromosomal instability in adenocarcinoma of the ileum arising from multifocal gastric heterotopia with gastritis cystica profunda. AB - Adenocarcinoma of the small intestine arising from heterotopic gastric mucosa is extremely rare. In this report, we present the case of a 68-year-old woman who complained of abdominal pain, weight loss and subileus. Gross examination of resected small bowel revealed multiple flat polypous lesions with cysts in the ileal submucosa, one of which containing an ulcerated, stenosing tumour. On microscopic examination, an adenocarcinoma of the ileum arising from multifocal gastric heterotopia with secondary gastritis cystica profunda was diagnosed. Comparative genomic hybridization of the adenocarcinoma revealed chromosomal gains at 1q, 3q, 5p, 8q, 11p, 12p, 13q and losses at Xp, 4q, 8p, 10p, 14q, 17p, 20p, compatible with a high degree of genomic instability. PMID- 20577833 TI - Alternatives to surgery for early stage non-small cell lung cancer-ready for prime time? AB - Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC), with lobectomy being the most oncologically sound resection. Medically inoperable patients and high-risk surgical candidates require effective alternatives to surgery; even operable patients may opt for less invasive options if they are proven to achieve similar outcomes to surgery. Minimally invasive local treatment modalities including dose-intensified conformal radiation therapy, most notably stereotactic ablative radiotherapy (SABR; also known as stereotactic body radiation therapy), and thermal ablation methods such as radiofrequency ablation (RFA) and microwave ablation (MWA) are emerging as promising treatment options whose roles in the treatment of early stage lung cancer are being defined. Early clinical experience and a rapidly growing body of prospective clinical trials, primarily in medically inoperable patients, are demonstrating encouraging effectiveness and safety outcomes in some cases approaching historical results with surgery. Given the very poor prognosis of the medically inoperable patient population, these alternatives to surgery, particularly SABR, are starting to be considered appropriate first-line therapy in properly selected patients, and prospective cooperative group trials to evaluate and optimize RFA and SABR in specific patient subsets are being conducted. For operable patients, prospective multi-center and cooperative groups trials of SABR are ongoing or completed, and international randomized trials of SABR vs. surgery have been initiated. Thus, promising alternatives to surgery for early stage NSCLC are ready for prime time evaluation in the setting of clinical trials, and participation in ongoing trials for both operable and medically inoperable patients is strongly encouraged. PMID- 20577834 TI - C-reactive protein levels before reduced-intensity conditioning predict outcome after allogeneic stem cell transplantation. AB - The prognostic value of CRP levels before conditioning for allogeneic stem-cell transplantation (ASCT) was evaluated. Reduced-intensity conditioning (RIC) was given to 205 patients and conventional myeloablative conditioning (MAC) to 299 patients. Most patients had an HLA-compatible related or unrelated donor. There were 287 males and 216 females, median age 36 (1-69) years. Most patients received peripheral blood stem cells. Increased CRP levels (>10 mg/L) were detected in 129 patients (26%). Overall survival (OS) and transplant-related mortality (TRM) were worse for RIC patients with elevated CRP (67 vs. 43%, p = 0.005, and 16 vs. 30%, p = 0.036) while no difference was seen in MAC patients. An infection at the start of conditioning was seen in 27 RIC patients. We identified a subgroup of patients with an infection and elevated CRP (n = 16) and these patients had the worst outcome. In multivariate analysis, both infection and elevated CRP was the strongest factor associated with OS (HR 3.27, p < 0.001) and TRM (HR 4.35, p < 0.001). No correlation between any outcome variable and CRP was seen in MAC-treated patients. CRP may be a good prognostic factor for outcome after RIC and ASCT. It should be analyzed before conditioning, especially in patients with coexisting infection since patients with increased CRP and infection seem to have a very poor outcome after ASCT. PMID- 20577835 TI - CD4-positive diffuse large B cell lymphoma identified by flow cytometry: two case reports. AB - We report two cases of diffuse large B cell lymphoma (DLBCL), both occurring in the small bowel, which coexpress PAX5, weak or no CD20 and the CD4 antigen. The CD4 was initially identified by flow cytometry and then confirmed by immunohistochemistry. CD4 is a representative marker for helper T-lymphocytes and is present on a subset of thymocytes, peripheral T cells and monocytes or macrophages. Unlike CD2 and CD5, no B cell fractions are known to express CD4. It might be hypothesized that the deregulated control of gene expression in malignant B cells, in particular PAX5, leads to the activation of some silent or repressed genes of T cell differentiation. Although lineage infidelity is described in some B lymphomas, it remains as an uncommon phenomenon; to our knowledge, cases reported here are the first two cases of DLBCL of the gastrointestinal tract coexpressing the CD4 antigen to be described to date. PMID- 20577836 TI - BK virus-associated nephropathy in an HIV-positive patient with gingival plasmablastic lymphoma. PMID- 20577837 TI - Ex vivo expansion and long-term hematopoietic reconstitution ability of sorted CD34+CD59+ cells from patients with paroxysmal nocturnal hemoglobinuria. AB - Autologous bone marrow transplantation (ABMT) for paroxysmal nocturnal hemoglobinuria (PNH) remains difficult so far. To expand residual normal CD34(+)CD59(+) cells isolated from patients with PNH and observe the long-term hematopoietic reconstruction ability of the expanded cells both ex vivo and in vivo, CD34(+)CD59(+) cells from 13 PNH patients and CD34(+) cells from 11 normal controls were separated from bone marrow mononuclear cells first by immunomagnetic microbeads and then by flow cytometry autoclone sorting. The cells were then cultivated under different conditions. The long-term hematopoietic supporting ability of expanded CD34(+)CD59(+) cells was evaluated by long-term culture in semi-solid medium in vitro and long-term engraftment in irradiated severe combined immunodeficiency (SCID) mice in vivo. The best combination of hematopoietic growth factors for ex vivo expansion was SCF + IL-3 + IL-6 + FL + Tpo + Epo. The most suitable time for harvest was on day 7. CD34(+)CD59(+) PNH cells retained strong colony-forming capacity even after expansion. The survival rate, complete blood cell count recovery on day 90, and human CD45 expression in different organs were similar between the irradiated SCID mice transplanted with expanded CD34(+)CD59(+) PNH cells and those with normal CD34(+) cells (P > 0.05) both in primary and secondary transplantation. These data provided a new potential way of managing PNH with ABMT. PMID- 20577838 TI - Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line. AB - The expression pattern of microRNAs (miRNAs) and their potential target genes were investigated in acute promyelocytic leukemia (APL) cell line NB4 cells during all-trans-retinoid acid (ATRA) treatment by using a miRNA microarrays platform and real-time quantitative PCR (RTQ-PCR). MiR-146a as one of the miRNAs down-regulated by ATRA during APL differentiation was identified. Direct interaction between miR146a and its predictive target gene Smad4 were confirmed by Luciferase assay. Down-regulation of miR-146a and upregulation of Smad4 at protein levels were demonstrated. These data suggested that miR-146a might influence proliferation of APL cells through TGF-beta1/Smad signal transduction pathway during ATRA induction. PMID- 20577839 TI - Imatinib for newly diagnosed chronic-phase chronic myeloid leukemia: results of a prospective study in Japan. AB - Although imatinib has become the current standard treatment for chronic myeloid leukemia (CML), there is limited information regarding its efficacy and safety among Japanese patients. We therefore conducted a prospective multi-center open label study of imatinib for Japanese patients with newly diagnosed chronic-phase CML (CP-CML). A total of 107 patients were enrolled and treated with imatinib at an initial daily dose of 400 mg. Eighty-three patients completed 3 years of study treatment. The cumulative rates of major cytogenetic response and complete cytogenetic response (CCyR) were 90.9 and 90.2% at 3 years, respectively. The safety profile was not very different from that reported in the IRIS study, although grade > or =3 neutropenia occurred relatively frequently (31.8 vs. 14.3%). Only seven patients discontinued the study due to adverse events, as did four patients due to insufficient efficacy. The 3-year probabilities of overall survival and progression-free survival were 93.2 and 91.4%, respectively. Higher average daily doses (i.e., > or =350 mg) were significantly associated not only with higher rates of achieving CCyR, but also with longer duration of CCyR. These findings confirm the clinical utility of imatinib in Japanese patients with newly diagnosed CP-CML, and suggest detrimental effect of low average daily dose on treatment results. PMID- 20577840 TI - Stem and progenitor cells in human umbilical cord blood. AB - Both stem cells and progenitor cells are present in umbilical cord blood (UCB) at a high frequency, making these cells a major target population for experimental and clinical studies. As the use of autologous or allogeneic hematopoietic stem cell transplantation in the treatment of various diseases has grown rapidly in recent years, the concept of UCB banking for future use has drawn increasing interest. Stem and progenitor cells derived from UCB offer multiple advantages over adult stem cells, such as their immaturity (which may play a significant role in reducing rejection after transplantation into a mismatched host) and ability to produce large quantities of homogeneous tissue or cells. These cells can also differentiate across tissue lineage boundaries into neural, cardiac, epithelial, hepatic, and dermal tissues. Human UCB provides an alternative cell source that is ethically acceptable and widely supported by the public. This paper summarizes the characteristics of human UCB-derived stem and progenitor cells and their potential therapeutic use for tissue and cell regeneration. PMID- 20577841 TI - Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy. AB - To examine the late effects and health-related quality of life of childhood cancer survivors (CCS) after radiotherapy (RT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: CCS treated with or without RT, and a general population matched for age, gender, residential area, and work status. The numbers in each group were 113, 72, and 1,000, respectively. The median ages of CCS at diagnosis and the time of the survey were 8 and 22 years, respectively. The mean final heights of males and females were significantly lower in CCS with RT than in the other 2 groups. Risk factors for a short stature were total body irradiation (TBI) [odds ratio (OR) 17.8, p < 0.001], spinal irradiation (OR 8.31, p = 0.033), and an age younger than 10 years at diagnosis. Late effects were observed in 68% of CCS with RT compared with 36% of CCS without RT. Multivariate analysis revealed that TBI was significantly associated with endocrine dysfunction (OR 12.3), skull and spinal irradiation with cognitive dysfunction (OR 16.1 and 11.5, respectively), and spinal irradiation with a short stature (OR 14.1), respectively. Physical dysfunction, psychological stress, and problems of social adaptation were observed in >50% of CCS with RT. PMID- 20577842 TI - The fate of grafting acetabular defects during revision total hip arthroplasty. AB - BACKGROUND: Acetabular defects are frequently grafted during revision THA. Previous studies using plain radiographs report high rates of graft incorporation. However, given plain radiographs underestimate osteolysis, it is unclear whether plain radiographs adequately reflect graft fill or incorporation. QUESTIONS/PURPOSES: We determined if (1) graft fill; or (2) incorporation (measured as graft-bone contact) differed with complete revision and grafting compared to liner exchange and grafting; (3) defect fill and incorporation could be assessed on plain radiographs; and (4) the cost of bone grafting differed with these two procedures. METHODS: We identified 40 patients who underwent revision THA for aseptic loosening or polyethylene wear and osteolysis, either with retention of a well-fixed cup or complete acetabular revision in which bone graft was used. Lesion size, percent fill, and graft healing was quantified from CT scans. A limited cost analysis was performed using the current hospital costs for implants, bone grafts, and bone graft substitutes. The minimum followup was 1 year (mean, 4.8 years; range, 1-11 years). RESULTS: The average defect fill was 30% (range, 0%-81%). The average percent of healing to host bone was 24% (range, 0-66%). Complete revisions had a higher percent defect fill compared to head/liner changes (47% versus 17%) as well as a higher degree of graft healing to host bone compared to head/liner changes (36% versus 14%). High resolution CT demonstrated lower percentages of defect fill and graft healing than previous reports based on plain radiographs. Bone grafting costs exceeded implant costs in the head/liner exchange group; however, the overall cost was higher in the complete revision group. CONCLUSIONS: Higher degrees of defect fill and healing were seen with complete revisions compared to head/liner exchanges. Compared to CT scans, plain radiograph assessment tended to overestimate defect fill and healing. PMID- 20577845 TI - Fecal polymerase chain reaction for Mycobacterium tuberculosis IS6110 to distinguish Crohn's disease from intestinal tuberculosis. AB - BACKGROUND: We have previously shown that amplification of Mycobacterium tuberculosis specific DNA (TB PCR) from feces reliably diagnosed intestinal tuberculosis. This study was undertaken to determine how well this test would distinguish intestinal tuberculosis from Crohn's disease in a country endemic for tuberculosis. METHODS: Consecutive patients with diagnoses of Crohn's disease and intestinal tuberculosis were enrolled, and the diagnoses confirmed by follow up. DNA was extracted from fecal samples and subjected to polymerase chain reaction TB PCR for IS6110 sequence which is specific for M. tuberculosis. RESULTS: Twenty one of 24 patients with intestinal tuberculosis and 5 of 44 patients with Crohn's disease tested positive by TB PCR. The sensitivity, specificity, positive predictive and negative predictive values for TB PCR in distinguishing tuberculosis from Crohn's disease were 0.79 (95% confidence interval 0.57-0.92), 0.88 (0.75-0.96), 0.79 (0.57-0.92) and 0.88 (0.75-0.96), respectively. A combination of fecal TB PCR with mycobacterial culture of mucosal biopsy specimens identified 23 of 24 (96.2%) of patients with intestinal TB, with sensitivity, specificity, positive predictive and negative predictive values (95% CI) of 0.95 (0.78-0.99), 0.88 (0.75-0.96), 0.82 (0.63-0.93) and 0.97 (0.86-0.99), respectively. CONCLUSION: Fecal TB PCR is a good screening test to distinguish intestinal tuberculosis from Crohn's disease. PMID- 20577843 TI - FoxO, autophagy, and cardiac remodeling. AB - In response to changes in workload, the heart grows or shrinks. Indeed, the myocardium is capable of robust and rapid structural remodeling. In the setting of normal, physiological demand, the heart responds with hypertrophic growth of individual cardiac myocytes, a process that serves to maintain cardiac output and minimize wall stress. However, disease-related stresses, such as hypertension or myocardial infarction, provoke a series of changes that culminate in heart failure and/or sudden death. At the other end of the spectrum, cardiac unloading, such as occurs with prolonged bed rest or weightlessness, causes the heart to shrink. In recent years, considerable strides have been made in deciphering the molecular and cellular events governing pro- and anti-growth events in the heart. Prominent among these mechanisms are those mediated by FoxO (Forkhead box containing protein, O subfamily) transcription factors. In many cell types, these proteins are critical regulators of cell size, viability, and metabolism, and their importance in the heart is just emerging. Also in recent years, evidence has emerged for a pivotal role for autophagy, an evolutionarily conserved pathway of lysosomal degradation of damaged proteins and organelles, in cardiac growth and remodeling. Indeed, evidence for activated autophagy has been detected in virtually every form of myocardial disease. Now, it is clear that FoxO is an upstream regulator of both autophagy and the ubiquitin-proteasome system. Here, we discuss recent advances in our understanding of cardiomyocyte autophagy, its governance by FoxO, and the roles each of these plays in cardiac remodeling. PMID- 20577844 TI - Clenbuterol induces cardiac myocyte hypertrophy via paracrine signalling and fibroblast-derived IGF-1. AB - The beta(2)-selective adrenoreceptor agonist clenbuterol promotes both skeletal and cardiac muscle hypertrophy and is undergoing clinical trials in the treatment of muscle wasting and heart failure. We have previously demonstrated that clenbuterol induces a mild physiological ventricular hypertrophy in vivo with normal contractile function and without induction of alpha-skeletal muscle actin (alphaSkA), a marker of pathological hypertrophy. The mechanisms of this response remain poorly defined. In this study, we examine the direct action of clenbuterol on cardiocyte cultures in vitro. Clenbuterol treatment resulted in increased cell size of cardiac myocytes with increased protein accumulation and myofibrillar organisation characteristic of hypertrophic growth. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed elevated mRNA expression of ANP and brain natriuretic peptide (BNP) but without change in alphaSkA, consistent with physiological hypertrophic growth. Clenbuterol-treated cultures also showed elevated insulin-like growth factor I (IGF-1) mRNA and activation of the protein kinase Akt. Addition of either IGF-1 receptor-blocking antibodies or LY294002 in order to inhibit phosphatidylinositol 3-kinase, a downstream effector of the IGF-1 receptor, inhibited the hypertrophic response indicating that IGF-1 signalling is required. IGF-1 expression localised primarily to the minor population of cardiac fibroblasts present in the cardiocyte cultures. Together these data show that clenbuterol acts to induce mild cardiac hypertrophy in cardiac myocytes via paracrine signalling involving fibroblast-derived IGF-1. PMID- 20577847 TI - 2009 ARVO-JOS Symposium. PMID- 20577846 TI - Oxidative stress in mouse liver caused by dietary amino acid deprivation: protective effect of methionine. AB - The aim of this work was to evaluate the effects of a diet depleted of amino acids (protein-free diet, or PFD), as well as the supplementation with methionine (PFD+Met), on the antioxidant status of the female mouse liver. With this purpose, cytosolic protein spots from two-dimensional non-equilibrium pH gel electrophoresis were identified by several procedures, such as mass spectrometry, Western blot, gel matching and enzymatic activity. PFD decreased the contents of catalase (CAT), peroxiredoxin I (Prx-I), and glutathione peroxidase (GPx) by 67%, 37% and 45%, respectively. Gene expression analyses showed that PFD caused a decrease in CAT (-20%) and GPx (-30%) mRNA levels but did not change that of Prx I. It was also found that, when compared to a normal diet, PFD increased the liver contents of both reactive oxygen species (+50%) and oxidized protein (+88%) and decreased that of glutathione (-45%). Supplementation of PFD with Met prevented these latter effects to varying degrees, whereas CAT, Prx-I and GPx mRNA levels resulted unmodified. Present results suggest that dietary amino acid deprivation deranges the liver antioxidant defences, and this can be, in part, overcome by supplementation with Met. PMID- 20577848 TI - Anterior segment mechanisms of protection during herpes simplex virus 1 infection. PMID- 20577849 TI - Suppression of herpes simplex virus 1 reactivation in a mouse eye model by cyclooxygenase inhibitor, heat shock protein inhibitor, and adenosine monophosphate. PMID- 20577850 TI - Host-pathogen interactions in the cornea. PMID- 20577851 TI - Innate immunity of the ocular surface. PMID- 20577852 TI - Wound healing fibroblasts modulate corneal angiogenic privilege: interplay of basic fibroblast growth factor and matrix metalloproteinases in corneal angiogenesis. PMID- 20577853 TI - Corneal morphogenesis during development and wound healing. PMID- 20577854 TI - Biology of corneal endothelial cells in vivo and in vitro. PMID- 20577855 TI - Using synthesized onion lachrymatory factor to measure age-related decreases in reflex-tear secretion and ocular-surface sensation. AB - PURPOSE: To use synthesized onion lachrymatory factor (SOLF) to investigate age related changes in reflex-tear secretion and ocular-surface sensation. METHODS: We separated 91 healthy volunteers into four groups: groups A, age 20-29 years; B, 30-39; C, 40-49; and D, older than 50 years. We exposed one eye of each subject to SOLF and measured the elapsed time until the subject's limit of irritation tolerance (TLI) was reached and an increase in the tear meniscus radius (DeltaR). After the SOLF stimulus, corneal sensitivity was examined by Cochet-Bonnet esthesiometry (CB), and reflex-tear secretion was examined by the Schirmer I-test (ST). RESULTS: TLI was significantly shorter in group A than in the other groups (P < 0.0001), and the groups B and D also differed significantly from each other (P = 0.0013). The increase in DeltaR was significantly greater in group A than in group C (P = 0.0306) or D (P < 0.0001), and groups B (P = 0.0002) and C (P = 0.0308) also differed significantly from group D. There were no significant intergroup differences in the CB and ST results. CONCLUSIONS: An age related decrease in reflex-tear secretion and ocular-surface sensation was revealed by the SOLF test but could not be detected by either CB or the ST. PMID- 20577856 TI - Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications. AB - PURPOSE: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP 9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in conjunctival melanomas and their correlations with clinicopathologic parameters and prognosis. METHODS: Fourteen conjunctival melanoma tissue samples and nine conjunctival nevus tissue samples were stained immunohistochemically for MMP-2, MMP-9, and TIMP-1. Association of MMP-2, MMP-9, and TIMP-1 expression in melanoma tissues with clinical progression in terms of metastasis, recurrence, mitotic index, thickness, base diameter, and invasion depth was analyzed. RESULTS: In the melanoma group, 78.6% of samples showed a positive reaction for MMP-2, 85.7% for MMP-9, and 100% for TIMP-1. In the nevus group, 11.1% showed a positive reaction for MMP-2, 66.7% for MMP-9, and 100% for TIMP-1. MMP-2 expression was significantly more induced in conjunctival melanoma than in benign nevi (P = 0.002). In conjunctival melanoma, MMP-9 expression was higher in tumors >1.5 mm thick (P = 0.026) and TIMP-1 expression was higher in recurrent cases (P = 0.03). There was no significant correlation between the expression and metastasis during the follow-up period (mean, 5 years). CONCLUSION: MMP-2, MMP-9, and TIMP-1 were expressed in the majority of conjunctival melanomas, and MMP-2 might play a role in the development and clinical behavior of conjunctival melanoma. PMID- 20577857 TI - Peripheral exudative hemorrhagic chorioretinopathy in Korean patients. AB - BACKGROUND: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare condition characterized by either subretinal exudates or subretinal hemorrhage outside the macula. The objective of this case report is to describe PEHCR lesions in Korean patients. CASES: Five eyes of four patients are reviewed. OBSERVATIONS: All cases were characterized by either peripheral subretinal exudates or hemorrhage with age-related degeneration. Four of the lesions appeared as subretinal masses, and the other manifested as a large retinal pigment epithelial alteration combined with subretinal exudates and subretinal fibrosis. Two of the patients evidenced serious visual impairment induced by massive subretinal hemorrhage extending to the fovea. Visual acuity in the other three eyes studied remained stable. CONCLUSION: PEHCR appears to be a variant of age-related macular degeneration that occurs in Asians. Although PEHCR is known to be self-limiting, it frequently causes subfoveal extensions of subretinal blood and fluid. PMID- 20577858 TI - Axial growth and binocular function following bilateral lensectomy and scleral fixation of an intraocular lens in nontraumatic ectopia lentis. AB - PURPOSE: To evaluate binocular function (BF) and changes in axial length (AL) bilaterally in pseudophakic eyes of children after lensectomy and scleral fixation of an intraocular lens (IOL) for nontraumatic ectopia lentis. METHODS: In 15 children who had undergone bilateral lensectomy and scleral fixation of an IOL for nontraumatic ectopia lentis, AL was measured preoperatively and at last follow-up, and BF was assessed at last follow-up. Axial growth was compared with the expected and observed patterns of normal eyes, and the results were compared between patients with isolated ectopia lentis and those with Marfan syndrome. RESULTS: Ten of the 15 patients had Marfan syndrome. Mean age at surgery was 5.2 +/- 2.4 years; mean follow-up was 51.7 +/- 29.2 months. A mean axial growth rate of 0.39 mm/year during 51.7 postoperative months was greater than the expected (0.07 mm/year) or the observed (0.09-0.24 mm/year) rates in age-matched normal eyes. The axial growth rates in isolated ectopia lentis patients and Marfan patients were not significantly different (P = 0.159). Binocular fusion and stereoacuity of < or =800 seconds of arc were achieved by nine patients, and worse or no BF was achieved by the remaining six patients. These six patients were significantly more likely to have pre- or postoperative anisometropia of > or =3.0 D (66.6%) than the other nine patients (0%). CONCLUSIONS: Because of greater than normal axial growth, more undercorrection of the IOL power is required than is usual in bilateral surgery for nontraumatic ectopia lentis. Good or moderate levels of postoperative BF were achieved in more than half of patients. PMID- 20577859 TI - Oncocytoma of the lacrimal gland: an Asian case. PMID- 20577860 TI - Levels of soluble CD14 and lipopolysaccharide-binding protein in human basal tears. PMID- 20577861 TI - Vascular endothelial growth factor concentrations in aqueous humor before and after subconjunctival injection of bevacizumab for neovascular glaucoma. PMID- 20577862 TI - Conjunctival nevus-like lesions originating from a sclerotomy site after 23-gauge transconjunctival sutureless vitrectomy. PMID- 20577863 TI - Bilateral cytomegalovirus retinitis with unilateral optic neuritis in Good syndrome. PMID- 20577864 TI - Analysis of cyclosporin A-induced reversible cortical blindness by diffusion weighted magnetic resonance imaging techniques. PMID- 20577865 TI - Bilateral exudative retinal detachment in Churg-Strauss syndrome controlled with intravenous immunoglobulin. PMID- 20577866 TI - Anterior ischemic optic neuropathy following intravitreal bevacizumab. PMID- 20577867 TI - [Quo vadis carotid artery stenting?]. PMID- 20577868 TI - Removal of selenium from Se enriched natural soils by a consortium of Bacillus isolates. AB - Four bacterial strains designated as SNTP-1, NS-2 to NS-4 were isolated from selenium contaminated soils of Nawanshahr-Hoshiarpur region of Punjab, India, by enrichment technique and a consortium was developed using these isolates. The isolates were observed to be belonging to Bacillus sp. In soil microcosm, complete removal was observed by the consortium in selenite augmented soils while the rate of removal with consortia in selenate treatment was 72% after 120 days. Population survival of isolates showed stability at lower treatments and decline at higher levels of Se enrichment. The consortium can, thus, be used for removal of Se contaminated sites. PMID- 20577869 TI - Ex-situ bioremediation of crude oil in soil, a comparative kinetic analysis. AB - Weathered crude oil (WCO) removals in shoreline sediment samples were monitored for 60 days in bioremediation experimentation. Experimental modeling was carried out using statistical design of experiments. At optimum conditions maximum of 83.13, 78.06 and 69.92% WCO removals were observed for 2, 16 and 30 g/kg initial oil concentrations, respectively. Significant variations in the crude oil degradation pattern were observed with respect to oil, nutrient and microorganism contents. Crude oil bioremediation were successfully described by a first-order kinetic model. The study indicated that the rate of hydrocarbon biodegradation increased with decrease of crude oil concentrations. PMID- 20577870 TI - Two species of commercial flatfish, winter flounder, Pleuronectes americanus, and American plaice, Hippoglossoides platessoides, as sentinels of environmental pollution. AB - Two species of marketable-size flatfish, winter flounder (Pleuronectes americanus) and American plaice (Hippoglossoides platessoides) from a fjord, were examined as sentinels for the effects of effluent discharged by a pulp and paper mill in Newfoundland, Canada. Reference samples for comparison were obtained from a pristine fjord. Condition factor, lymphocyte levels and the abundance of two intestinal parasites were significantly greater in flounder and plaice sampled at the reference site while macroscopic and microscopic lesions, and hepatic somatic indices were greater in flatfish taken from the contaminated site. These results suggest that both species of commercial flatfish are useful as sentinels for studying environmental pollution. PMID- 20577871 TI - Influence of environmental pollution on leaf properties of urban plane trees, Platanus orientalis L. AB - To investigate whether leaves of plane trees (Platanus orientalis) are damaged by traffic pollution, trees from a megacity (Mashhad, Iran) and a rural area were investigated. Soil and air from the urban centre showed enrichment of several toxic elements, but only lead was enriched in leaves. Leaf size and stomata density were lower at the urban site. At the urban site leaf surfaces were heavily loaded by dust particles but the stomata were not occluded; the cuticle was thinner; other anatomical properties were unaffected suggesting that plane trees can cope with traffic exhaust in megacities. PMID- 20577872 TI - Osteoporosis quality indicators using healthcare utilization data. AB - SUMMARY: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying dual-energy X-ray absorptiometry (DXA) testing (sensitivity = 98%, specificity = 93%) and osteoporosis pharmacotherapy (kappa = 0.81) with minimal measurement error. INTRODUCTION: In osteoporosis, key quality indicators among older women include risk assessment by DXA and/or pharmacotherapy within 6 months following fracture. METHODS: The purpose of this study was to examine healthcare utilization data for use as quality indicators of osteoporosis management. We linked data from 858 community-dwelling women aged over 65 years who completed a standardized telephone interview about osteoporosis management to their healthcare utilization (medical and pharmacy claims) data. Agreement between self-report of osteoporosis pharmacotherapy and pharmacy claims was examined using kappa statistics. We examined the sensitivity and specificity of medical claims to identify DXA testing as well as the sensitivity and specificity of medical and pharmacy claims to identify those with DXA-documented osteoporosis (T-score <= -2.5). RESULTS: Participants were aged 75 (SD = 6) years on average; 96% were Caucasian. Agreement between self-report and claims-based osteoporosis pharmacotherapy was very good (kappa = 0.81; 95% CI = 0.76, 0.86). The sensitivity of medical claims to identify DXA testing was 98% (95% CI = 95.9, 99.1), with estimated specificity of 93% (95% CI = 89.8, 95.4). We abstracted DXA results from test reports of 359 women, of whom 114 (32%) were identified with osteoporosis. Medical (osteoporosis diagnosis) and pharmacy (osteoporosis pharmacotherapy) claims within a year after DXA testing had a sensitivity of 80% (95% CI = 71.3, 86.8) and specificity of 72% (95% CI = 66.2, 77.8) to identify DXA-documented osteoporosis. CONCLUSION: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying DXA testing and osteoporosis pharmacotherapy (care processes) with minimal measurement error. However, medical and pharmacy claims alone do not provide a good means for identifying women with underlying osteoporosis. PMID- 20577873 TI - Gene-gene interaction between CD40 and CD40L reduces bone mineral density and increases osteoporosis risk in women. AB - SUMMARY: We have analysed the association of single-nucleotide polymorphisms (SNPs) in CD40 and CD40L genes with bone mineral density (BMD) in our women. Results showed that women with TT genotype for rs1883832 (CD40) and for rs1126535 (CD40L) SNPs displayed reduced BMD and increased risk for osteopenia/osteoporosis. Our data notwithstanding, the results need to be replicated. INTRODUCTION: Recent data have revealed that the CD40/CD40L system can be implicated in bone metabolism regulation. Moreover, we previously demonstrated that rs1883832 in the CD40 gene was significantly associated with BMD and osteoporosis risk. The objective of the present work was to determine whether polymorphisms in CD40 and CD40L genes are associated with BMD and osteoporosis risk. METHODS: We conducted an association study of BMD values with SNPs in CD40 and CD40L genes in a population of 811 women of which 693 and 711 had femoral neck (FN) and lumbar spine (LS) densitometric studies, respectively. RESULTS: Women with the TT genotype for rs1883832 (CD40) showed a reduction in FN BMD (P = 0.005) and LS-BMD (P = 0.020) when compared with women with the CC/CT genotype. Moreover, we found that rs1126535 (CD40L) was significantly associated with LS-BMD so that women with the TT genotype displayed lower BMD (P = 0.014) than did women with the CC/CT genotype. Interestingly, we have found a strong interaction between polymorphisms in these genes. Thus, women with the TT genotype for both rs1883832 and rs1126535 SNPs (TT + TT women) showed a lower age adjusted BMD (Z-score) for FN (P = 0.0007) and LS (0.007) after adjusting by years since menopause, body mass index, smoking and menopausal status, densitometer type, hormone replacement therapy (HRT) use and HRT duration and after making the Bonferroni adjustment for multiple comparisons than did the remaining women. Logistic regression analysis adjusted by these covariates showed that TT + TT women had increased risk for FN (odds ratio (OR) = 2.76; P = 0.006) and LS (OR = 2.39; P = 0.020) osteopenia or osteoporosis than did the other women. CONCLUSIONS: Our results suggest that interaction between genetic variants in the CD40 and CD40L genes exerts a role on BMD regulation. Further studies, which we welcome, are needed to replicate these data in other populations. PMID- 20577874 TI - Low-frequency axial ultrasound velocity correlates with bone mineral density and cortical thickness in the radius and tibia in pre- and postmenopausal women. AB - Axial transmission velocity of a low-frequency first arriving signal (V (LF)) was assessed in the radius and tibia of 254 females, and compared to site-matched pQCT measurements. V (LF) best correlated with cortical BMD, but significantly also with subcortical BMD and cortical thickness. Correlations were strongest for the radius in postmenopausal females. INTRODUCTION: Ultrasonic low-frequency (LF; 0.2-0.4 MHz) axial transmission, based on the first arriving signal (FAS), provides enhanced sensitivity to thickness and endosteal properties of cortical wall of the radius and tibia compared to using higher frequencies (e.g., 1 MHz). This improved sensitivity of the LF approach has not yet been clearly confirmed by an in vivo study on adult subjects. The aims of the present study were to evaluate the extent to which LF measurements reflect cortical thickness and bone mineral density, and to assess whether an individual LF measurement can provide a useful estimate for these bone properties. METHODS: Velocity of the LF FAS (V (LF)) was assessed in the radius and tibia shaft by a new ultrasonometer (CV(RMS) = 0.5%) in a cross-sectional study involving 159 premenopausal (20-58 years) and 95 postmenopausal females (45-88 years). Site-matched volumetric total bone mineral density (BMD), cortical bone mineral density (CBMD), subcortical bone mineral density (ScBMD) and cortical thickness (CTh) were assessed using pQCT. RESULTS: For the postmenopausal females, V (LF) correlated best with CBMD in the radius (R = 0.850, p < 0.001), but significantly also with ScBMD and CTh (R = 0.759 and R = 0.761, respectively; p < 0.001). Similar trends but weaker correlations were observed for the tibia and for the premenopausal women. CONCLUSIONS: The LF assessment, with an optimal excitation frequency, thus provided good prediction of both cortical thickness and subcortical bone material properties. These results suggest that the LF approach does indeed have enhanced sensitivity for detecting osteoporotic changes that occur deep in the endosteal bone. PMID- 20577875 TI - Risk Management Plans: are they a tool for improving drug safety? AB - PURPOSE: In 2005, new European legislation authorised Regulatory Agencies to require drug companies to submit a risk management plan (RMP) comprising detailed commitments for post-marketing pharmacovigilance. The aim of the study is to describe the characteristics of RMP for 15 drugs approved by the European Medicines Agency (EMA) and their impact on post-marketing safety issues. METHODS: Of the 90 new Chemical Entities approved through a centralised procedure by the EMA during 2006 and 2007, 15 of them were selected and their safety aspects and relative RMPs analysed. All post-marketing communications released for safety reasons related to these drugs were also considered. RESULTS: A total of 157 safety specifications were established for the drugs assessed. Risk minimisation activities were foreseen for 5 drugs as training activities. Post-marketing safety issues emerged for 12 of them, leading to 39 type II variations in Summary of Product Characteristics (SPC). Nearly half of such variations, 19 (49%), concerned safety aspects not envisaged by the RMPs. Besides this, 9 Safety Communications were published for 6 out of 15 drugs assessed. CONCLUSION: The present study reveals several critical points on the way RMPs have been implemented. Several activities proposed by the RMPs do not appear to be adequate in dealing with the potential risks of drugs. Poor communication of risk to practitioners and to the public, and above all limited transparency for the total assessment of risk, seem to transform RMPs into a tool to reassure the public when inadequately evaluated drugs are granted premature marketing authorisation. PMID- 20577876 TI - Effects of liming on potential oxalate secretion and iron chelation of beech ectomycorrhizal root tips. AB - Liming is used to counteract forest decline induced by soil acidification. It consists of Ca and Mg input to forest soil and not only restores tree mineral nutrition but also modifies the availability of nutrients in soil. Ectomycorrhizal (ECM) fungi are involved in mineral nutrient uptake by trees and can recover them through dissolution of mineral surface. Oxalate and siderophore secretion are considered as the main agents of mineral weathering by ECMs. Here, we studied the effects of liming on the potential oxalate secretion and iron complexation by individual beech ECM root tips. Results show that freshly excised Lactarius subdulcis root tips from limed plots presented a high potential oxalate exudation of 177 MUM tip(-1) h(-1). As this ECM species distribution is very dense, it is likely that, in the field, oxalate concentrations in the vicinity of its clusters could be very high. This points out that not only extraradical mycelium but also ECM root tips of certain species can contribute significantly to mineral weathering. Nonmetric multidimensional scaling (NMDS) separated potential oxalate production by ECM root tips in limed and untreated plots, and this activity was mainly driven by L. subdulcis ECMs, but NMDS on potential activity of iron mobilization by ECM root tips did not show a difference between limed and untreated plots. As the mean oxalate secretion did not significantly correlated with the mean iron mobilization by ECM morphotype, we conclude that iron complexation was due to either other organic acids or to siderophores. PMID- 20577877 TI - CD8+ T cell recognition of polymorphic wild-type sequence p53(65-73) peptides in squamous cell carcinoma of the head and neck. AB - The TP53 tumor suppressor gene contains a well-studied polymorphism that encodes either proline (P) or arginine (R) at codon 72, and over half of the world's population is homozygous for R at this codon. The wild-type sequence (wt) p53 peptide, p53(65-73), has been identified as a CD8+ T cell-defined tumor antigen for use in broadly applicable cancer vaccines. However, depending on the TP53 codon 72 polymorphism of the recipient, the induced responses to the peptides incorporating R (p53(72R)) or P (p53(72P)) can be "self" or "non-self." Thus, we sought to determine which wt p53(65-73) peptide should be used in wt p53-based cancer vaccines. Despite similar predicted HLA-A2-binding affinities, the p53(72P) peptide was more efficient than the p53(72R) peptide in HLA-A2 stabilization assays. In vitro stimulation (IVS) of CD8+ T cells obtained from healthy HLA-A2(+) donors with these two peptides led to the generation of CD8+ T cell effectors in one-third of the samples tested, at a frequency similar to the responsiveness to other wt p53 peptides. Interestingly, regardless of their p53 codon 72 genotype, CD8+ T cells stimulated with either p53(72P) or p53(72R) peptide were cross-reactive against T2 cells pulsed with either peptide, as well as HLA-A2(+) head and neck cancer (HNC) cell lines presenting p53(72P) and/or p53(72R) peptides for T cell recognition. Therefore, the cross-reactivity of CD8+ T cells for the polymorphic wt p53(65-73) peptides, irrespective of their p53 codon 72 polymorphism, suggests that employing either peptide in wt p53-based vaccines can result in efficient targeting of this epitope. PMID- 20577878 TI - Cetuximab-dependent ADCC in cancer: dream or reality? PMID- 20577879 TI - Accuracy and reliability of different methods to evaluate the acetabular cup version from plain radiographs. AB - PURPOSE: The purpose of this study was to compare different methods of evaluating the version of a metallic acetabular cup from plain radiographs and to compare them regarding their accuracy, inter- and intra-observer reliability. METHODS: Conventional anterior-posterior radiographs were taken of a phantom-model at different defined ante- and retroversion angles of the acetabular cup. The version angles of the acetabular cup were derived according to four different established methods from the radiographs by five independent examiners. RESULTS: We were able to determine the radiographic version with the greatest accuracy according to a modified technique of Pettersson et al. Furthermore, we found the highest intra- and inter-observer reliability using this technique. CONCLUSIONS: A modified technique of Pettersson et al. broadens the spectrum of applicability for the radiographic evaluation of the version angle of metal-backed acetabular cups in comparison to the originally introduced method. In clinical practice, however, the significance of deriving the cup position from standard radiographs should not be over-estimated and therefore a computed tomography should be performed in certain critical cases. PMID- 20577880 TI - PET/CT in primary musculoskeletal tumours: a step forward. AB - Hybrid imaging with combined positron emission tomography/computed tomography (PET/CT) plays an important role in the staging and management of a wide variety of solid tumours. However, its use in the evaluation of musculoskeletal malignancy has not yet entered routine clinical practice. Cross-sectional imaging with magnetic resonance imaging (MR) and computed tomography have well established roles but there is increasing evidence for the selective use of PET/CT in the management of these patients. The aims of this article are to review the current evidence and clinical applications of PET/CT in primary musculoskeletal tumours and discuss potential future developments using novel PET tracers and integrated PET/MR. PMID- 20577881 TI - Clinical implications of microvascular obstruction and intramyocardial haemorrhage in acute myocardial infarction using cardiovascular magnetic resonance imaging. AB - OBJECTIVES: To investigate the clinical implications of microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) in acute myocardial infarction (AMI). METHODS: Ninety patients with a first AMI undergoing primary percutaneous coronary intervention (PCI) were studied. T2-weighted, cine and late gadolinium enhanced cardiovascular magnetic resonance imaging was performed at 5 +/- 2 and 103 +/- 11 days. Patients were categorised into three groups based on the presence or absence of MVO and IMH. RESULTS: MVO was observed in 54% and IMH in 43% of patients, and correlated significantly (r = 0.8, p < 0.001). Pre-PCI thrombolysis in myocardial infarction 3 flow was only observed in MVO(-)/IMH(-) patients. Infarct size and impairment of systolic function were largest in MVO(+)/IMH(+) patients (n = 39, 23 +/- 9% and 47 +/- 7%), smallest in MVO(-)/IMH( ) patients (n = 41, 8 +/- 8% and 55 +/- 8%) and intermediate in MVO(+)/IMH(-) patients (n = 10, 16 +/- 7% and 51 +/- 6%, p < 0.001). LVEF increased in all three subgroups at follow-up, but remained intermediate in MVO(+)/IMH(-) and was lowest in MVO(+)/IMH(+) patients. Using random intercept model analysis, only infarct size was an independent predictor for adverse LV remodelling. CONCLUSIONS: Intramyocardial haemorrhage and microvascular obstruction are strongly related. Pre-PCI TIMI 3 flow is less frequently observed in patients with MVO and IMH. Only infarct size was an independent predictor of LV remodelling. PMID- 20577882 TI - Phonotaxis to male's calls embedded within a chorus by female gray treefrogs, Hyla versicolor. AB - During the reproductive season, male Hyla versicolor produce advertisement calls to attract females. Females exhibit phonotaxis and approach the individual callers, resulting in amplexus. For frogs that call from dense choruses, the extent to which and the range from which a male's advertisement call within a chorus can be heard by a receptive female leading to phonotaxis is unclear. We investigated females' responses to natural choruses in the field and found that they were attracted and showed directed orientation to breeding choruses at distances up to 100 m. To assess the role of acoustic cues in the directed orientation, we conducted acoustic playback experiments in the laboratory using conspecific call and noise as stimuli, as well as chorus sounds (that contained calls from a focal male) recorded at various distances, all played at naturalistic intensities. Using two response metrics (females' normalized response times and their phonotaxis trajectories) we found that, unlike the field experiments, females oriented and were attracted to chorus sounds from 1 to 32 m only, but not from >32 m, or to band-limited noise. Possible reasons for the observed difference in phonotaxis behavior in the two experimental conditions were discussed. PMID- 20577883 TI - Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. AB - BACKGROUND: Insulin resistance is a common symptom of metabolic diseases such as obesity, type 2 diabetes and hyperlipidemia. AIM OF THE STUDY: We investigated whether Gastrodia elata Blume water extract(GEB), containing phenolic compounds, had a beneficial action on insulin resistance in male Sprague-Dawley rats fed a high fat diet(HFD) and determined how this effect was produced. In addition, the bioactive candidates involved were identified. METHODS: Rats fed HFD were daily administered with 0.3 g GEB(GEB-L), 1 g GEB(GEB-H), or 1 g cellulose(control) per kg body weight for 8 weeks, while rats in the fourth group were fed a low fat diet(LFD). In vitro study, 4 major components of GEB were tested for their impact on fat accumulation. RESULTS: Rats in the control group exhibited a higher weight gain of epididymal and retroperitoneal fat pads than those fed LFD, while GEB prevented such an increment in a dose-dependent manner. GEB-H significantly decreased energy intake partly through potentiating STAT3 phosphorylation and attenuating AMPK phosphorylation in the hypothalamus. GEB-H also increased energy expenditure with the increase in fat oxidation. GEB-H increased whole body glucose disposal rates and decreased hepatic glucose output compared to the control. Among the major components of GEB, 4-hydroxybenzaldehyde and vanillin decreased triglyceride accumulation by modulating the expression of genes involved in fat metabolism in 3T3-L1 adipocytes. They increased insulin stimulated glucose uptake to reduce insulin resistance. CONCLUSIONS: GEB-H, mainly as a result of the action of 4-hydroxybenzaldehyde and vanillin, reduces insulin resistance by decreasing fat accumulation in adipocytes by activating fat oxidation and potentiating leptin signaling in diet-induced obese rats. PMID- 20577884 TI - Morphological docking of secretory vesicles. AB - Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis, neurotransmitter-containing vesicles dock to the target membrane. In electron micrographs of neurons and neuroendocrine cells, like chromaffin cells many synaptic vesicles (SVs) and large dense-core vesicles (LDCVs) are docked. For many years the molecular identity of the morphologically docked state was unknown. Recently, we resolved the minimal docking machinery in adrenal medullary chromaffin cells using embryonic mouse model systems together with electron microscopic analyses and also found that docking is controlled by the sub membrane filamentous (F-)actin. Currently it is unclear if the same docking machinery operates in synapses. Here, I will review our docking assay that led to the identification of the LDCV docking machinery in chromaffin cells and also discuss whether identical docking proteins are required for SV docking in synapses. PMID- 20577885 TI - Toward the roles of store-operated Ca2+ entry in skeletal muscle. AB - Store-operated Ca(2+) entry (SOCE) has been found to be a rapidly activated robust mechanism in skeletal muscle fibres. It is conducted across the junctional membranes by stromal interacting molecule 1 (STIM1) and Orai1, which are housed in the sarcoplasmic reticulum (SR) and tubular (t-) system, respectively. These molecules that conduct SOCE appear evenly distributed throughout the SR and t system of skeletal muscle, allowing for rapid and local control in response to depletions of Ca(2+) from SR. The significant depletion of SR Ca(2+) required to reach the activation threshold for SOCE could only be achieved during prolonged bouts of excitation-contraction coupling (EC coupling) in a healthy skeletal muscle fibre, meaning that this mechanism is not responsible for refilling the SR with Ca(2+) during periods of fibre quiescence. While Ca(2+) in SR remains below the activation threshold for SOCE, a low-amplitude persistent Ca(2+) influx is provided to the junctional cleft. This article reviews the properties of SOCE in skeletal muscle and the proposed molecular mechanism, assesses its potential physiological roles during EC coupling, namely refilling the SR with Ca(2+) and simple balancing of Ca(2+) within the cell, and also proposes the possibility of SOCE as a potential regulator of t-system and SR membrane protein function. PMID- 20577887 TI - Interdural haemorrhage of the posterior fossa due to infraclinoidal carotid artery aneurysm rupture. AB - Several anatomical studies indicate that the intracranial pachimeninges consist of two dural layers joined together, which divide while bordering the venous sinuses, therefore located in an interdural space. We present here an uncommon case of haematoma due to rupture of an infraclinoidal internal carotid artery aneurysm. The dome of the aneurysm leaned against the posterior wall of the cavernous sinus and, following laceration, pierced the inner dural layer and caused its detachment from the periosteal layer, thus determining a truly interdural haematoma which progressively involved the whole posterior fossa. A 42 year-old female was admitted to our institution with a recent history of thunderclap headache and right ophthalmoparesis. Two cerebral computerised scan tomographies performed elsewhere tested negative for subarachnoid haemorrhage. A cerebral magnetic resonance imaging (MRI) showed a thin collection of blood adjacent to the clivus and all along the wall of the posterior fossa and foramen magnum. A right infraclinoid internal carotid artery aneurysm was also diagnosed, subsequently better highlighted on angiography. The patient underwent surgery with aneurysm clipping. Post-operative course was uneventful, and control angiography showed complete exclusion of the aneurysm from blood circulation. The patient was discharged 5 days later. At 3 months follow-up ophthalmoplegia had disappeared, and the patient had fully recovered. The possibility of a truly interdural location, particularly in cases of non-traumatic parasellar or clival haematomas, must be included in the differential diagnosis of posterior fossa extra-axial haemorrhages. MRI is the test of choice for diagnostic purposes. PMID- 20577888 TI - Procedural predictors of delayed cerebral infarction after intra-arterial vasodilator infusion for vasospasm following aneurysmal subarachnoid hemorrhage. AB - PURPOSE: The goals of this study were to identify predictors of delayed cerebral infarction in aneurysmal SAH after intra-arterial (IA) vasodilator infusion and to select proper parameters for treatment success. METHODS: Forty-three patients qualified for review. Cerebral infarction was determined by DWI within 1 week of angiographic vasospasm. RESULTS: Infarction developed in 18 of the 43 patients (41.9%) after IA vasodilator infusion and was associated with a high degree of proximal vessel residual narrowing and angiographic cerebral circulation time (CCT) prolongation at the end of IA vasodilator infusion (p < 0.001). A high degree of proximal residual narrowing (p = 0.018; odds ratio = 1.071; 95% confidence interval [CI] 1.012-1.123) and CCT prolongation at the end of the procedure (p = 0.007; odds ratio = 2.203; 95% CI 1.254-4.232) were found to be predictors of infarction by multivariate analysis. Furthermore, receiver operating characteristic (ROC) curves showed that both variables predicted the development of infarction (proximal vessel residual narrowing, area under the ROC curve [AUC], 0.828; CCT, AUC, 0.866). When proximal vessel narrowing of >30% or a CCT of >7 s by final angiography during IA vasodilator infusion were used as a threshold, the negative predictive value for infarction was 88.9% (95% CI 65.3 98.6%), and when narrowing was >30% and CCT was >7 s, the probability of subsequent cerebral infarction was 100% (95% CI 71.7-100%). CONCLUSIONS: Angiographic CCT and residual narrowing at the end of IA vasodilator infusion were found to predict the subsequent occurrence of cerebral infarction. The authors suggest that residual narrowing of 30% and a CCT of 7 s could be used as a minimum indicator of IA vasodilator infusion endpoints. PMID- 20577889 TI - Maintenance of Y receptor dimers in epithelial cells depends on interaction with G-protein heterotrimers. AB - Treatment of CHO cells expressing human Y receptors (Y(1), Y(2) or Y4 subtype) with pertussis toxin results in a large decrease in functional receptors, with a preferential loss of heteropentameric assemblies of receptor dimers and G-protein trimers. This occurs in parallel to inactivation of the nucleotide site of Gi alpha subunits, with a half period of about 4 h. The loss could be mainly due to proteolysis at the level of recycling/perinuclear endosomes, and of receptor completion in the ER, since it is reduced by co-treatment with ammonium chloride, an inhibitor of particulate proteinases. Antagonists do not strongly decrease the heteropentameric fraction. These findings indicate that the upkeep of Y receptor dimers in epithelial cell lines depends on the association of receptor oligomers with functional Gi alpha subunits. This interaction could use the juxtamembrane helix 8 in the fourth intracellular domain, and could also be supported by the C terminal helix of the third intracellular loop, as outlined in the companion review (Parker et al., Amino Acids, doi: 10.1007/s00726-010-0616-1 , 2010). PMID- 20577890 TI - Evaluation of two-center Coulomb and hybrid integrals over complete orthonormal sets of Psialpha-ETO using auxiliary functions. AB - By the use of ellipsoidal coordinates, the two-center Coulomb and hybrid integrals over complete orthonormal sets of Psialpha-ETO exponential type orbitals arising in ab initio calculations of molecules are evaluated, where alpha = 1,0, -1, -2, ...,. These integrals are expressed through the auxiliary functions Q(ns)(q) and G(-ns)(q). The comparison is made with some values of integrals for Slater type orbitals the computation results of which are in good agreement with those obtained in the literature. The relationships obtained are valid for the arbitrary quantum numbers, screening constants and location of orbitals. Closed form expressions for two-center Coulomb and hybrid integrals for 1s and 2s orbitals with alpha = 1 are also presented. As an example of application, the Hartree-Fock-Roothaan calculations for the ground state of H(2) molecule are carried out with alpha = 1 and alpha = 0. PMID- 20577891 TI - Validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-31) in Chinese. AB - QUALEFFO-31 is a recently developed disease-specific instrument derived from QUALEFFO-41 and intended to have improved efficacy and response rates. We aimed to validate QUALEFFO-31 in Chinese and examine the use of QUALEFFO-31 in clinical practice. This questionnaire was translated into Chinese and applied to 118 case control pairs aged between 50 and 85 years with prevalent osteoporotic vertebral fractures to evaluate its validity, repeatability, and discriminatory ability. It was also used to evaluate the quality of life (QOL) of 69 case-control trios with prevalent clinical and morphometric fractures. The QOL of all subjects was concurrently assessed using SF-36 for comparison. QUALEFFO-31 had good internal consistency with adequate convergent and discriminatory validity. The median test retest repeatability ranged from 0.65-0.85. In general, there were good correlations between QUALEFFO-31 and SF-36. ROC curve analysis revealed that QUALEFFO-31 had significant ability to discriminate between clinical fracture subjects versus morphometric fracture subjects and controls. QUALEFFO-31 also demonstrated higher discriminatory capacity for pain. Subjects with clinical vertebral fractures (CVFs) had a significant reduction in QOL compared with other subjects. The QUALEFFO-31 is a useful tool for assessing QOL in Chinese. It was well accepted and significantly predictive of subjects with CVFs. PMID- 20577892 TI - A sarcoidosis patient with hand involvement and large pulmonary lymph nodes: results of 1-year treatment with methotrexate. AB - Sarcoidosis infrequently involves the phalanges and the adjacent soft tissue. The management of bone lesions is not clear. We present herein the results of methotrexate therapy applied for 1 year in a sarcoidosis patient with hand involvement and large hilar lymphadenopathies. PMID- 20577893 TI - Dimorphisms and self-incompatibility in the distylous species Palicourea demissa (Rubiaceae): possible implications for its reproductive output. AB - Distyly has been interpreted as a mechanism that favors cross-fertilization. In this research we describe floral attributes and ancillary floral polymorphisms typically associated to heterostylous plants in Palicourea demissa (Rubiaceae), a distylous shrub of the Venezuelan Andes cloud forests. A hand-pollination experiment was done to evaluate self- and intramorph incompatibility and female reproductive output in both floral morphs. The studied population was morphologically distylous but morph differences in most ancillary floral polymorphisms and reciprocity of the sexual organ heights were found. The floral morphs were self-incompatible and did not differ in fruit set under controlled cross-pollination conditions, but at the population level they exhibited imperfect reciprocal herkogamy. Fruits and seeds of short-styled plants were larger than those of long-styled plants and fruit set was higher in short-styled plants under natural conditions, suggesting a higher reproductive potential among short-styled plants. Given the 1:1 morph ratio within the studied population, further evidence is needed to determine the influence of floral visitors and seed dispersers in the expression of heterostyly in P. demissa under natural conditions. PMID- 20577894 TI - Anti-tumour effects of xanthone derivatives and the possible mechanisms of action. AB - To explore the potential anti-tumour activities of xanthone derivatives, 26 hydroxylxanthones and benzoxanthones and their structurally modified analogues were examined for potential cytotoxic activities against eight human cancer cell lines. Most of the xanthone derivatives exhibited a higher degree of cytotoxicity on HepG2 cells than on the other seven cancer cell lines. Compound 24 (1,3,7 Trihydroxy-12H-benzo[b] xanthen-12-one) showed the highest degree of cytotoxicity of the tested compounds against HepG2 cells and demonstrated good tumour specificity by exhibiting a much higher degree of cytotoxicity against HepG2 cells than against normal liver cells (L02). Several valuable structure-activity relationships were derived from the cytotoxicity data. In addition, we found that compound 24 could downregulate the expression of the Mcl-1 protein, induce changes in the mitochondrial membrane potential and induce apoptosis in HepG2 cells via the mitochondrial pathway. Compound 24 was also shown to inhibit topoisomerase (topo) II activity and downregulate the levels of both topo II mRNA and protein in HepG2 cells. The present results suggest that due to its potent cytotoxicity and good tumour selectivity, compound 24 may be exploited as a potential lead compound in the development of a new anti-tumour agent with specific activity against liver cancer. PMID- 20577895 TI - Diversity and evolution of Ty1-copia retroelements in representative tribes of Bambusoideae subfamily. AB - Ty1-copia retroelements have been found in all major plants and are largely responsible for the huge differences in the genome size. In this study we isolated and sequenced Ty1-copia reverse transcriptase (rt) gene fragments from 44 representative species of bamboo and nine cultivars or forms of Phyllostachys pubescens. Phylogenetic analysis of 72 distinct Ty1-copia rt sequences showed that Ty1-copia retroelements were widespread, diverse and abundant in these species of Bambusoideae subfamily. In addition, a molecular phylogeny of the species of the Bambusoideae subfamily was established by using the internal transcribed spacer sequences of nuclear ribosomal DNA (ITS) sequences. The comparison between ITS- and Ty1-copia rt- based trees is obviously incongruent. The results suggested either the existence of horizontal transfer events between phylogenetically distant species, or an ancestral Ty1-copia retroelement polymorphism followed by different evolution and stochastic losses. PMID- 20577896 TI - Anoikis triggers Mdm2-dependent p53 degradation. AB - The extracellular matrix (ECM) plays a key role in cell-cell communication and signaling, and the signals it propagates are important for tissue remodeling and survival. However, signals from disease-altered ECM may lead to anoikis-apoptotic cell death triggered by loss of ECM contacts. Previously, we found that an altered fibronectin matrix triggers anoikis in human primary ligament cells via a pathway that requires p53 transcriptional downregulation. Here we show that this p53 reduction is suppressed by transfecting cells with Mdm2 antisense oligonucleotides or small interfering RNA. Similar results were found in cells treated to prevent p53 and Mdm2 interactions. When p53 was overexpressed in cells lacking Mdm2 and p53, p53 levels were unaffected by anoikis conditions. However, cells cotransfected with p53 and wild type Mdm2, but not a mutant Mdm2, exhibited decreased p53 levels in response to anoikis conditions. Thus, cells under anoikis conditions undergo p53 degradation that is mediated by Mdm2. PMID- 20577897 TI - Relational victimization and depressive symptoms in adolescence: moderating effects of mother, father, and peer emotional support. AB - Adolescence heralds a unique period of vulnerability to depressive symptoms. This longitudinal study examined relational victimization in adolescents' peer relationships as a unique predictor of depressive symptoms among a primarily (85%) Caucasian sample of 540 youth (294 females) concurrently and across a 6 year period. The moderating effects of emotional support received from mothers, fathers, and peers on the association between relational victimization and adolescents' depressive symptoms were also investigated. Findings revealed that adolescents who were relationally victimized consistently had higher depressive symptoms than their non-victimized peers. However, high levels of emotional support from fathers buffered this relationship over time. Emotional support from mothers and peers also moderated the longitudinal relationship between relational victimization and depressive symptoms, with high levels of support predicting increases in adolescents' symptoms. Relational victimization presents a clear risk for depressive symptoms in adolescence, and emotional support may serve either a protective or vulnerability-enhancing role depending on the source of support. PMID- 20577898 TI - Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium. AB - Angiotensin-converting enzyme (ACE) inhibitors improve outcomes in patients with coronary artery disease (CAD), heart failure, and hypertension. This short review examines clinical evidence for such effects and the underlying mechanism of action. One potential mode of action for ACE inhibitors in CAD is blood pressure reduction. However, recent data suggest that the effects of ACE inhibitors on the endothelium may also be relevant in attenuating the progression of atherosclerosis. In CAD, chronic overexpression of tissue ACE disrupts the angiotensin II/bradykinin balance with a net result of endothelial dysfunction, mainly due to an increased rate of apoptosis. An imbalance between endothelial apoptosis (death) and its renewal from the bone marrow (life) causes discontinuity of the endothelial layer, favoring the initiation and progression of a biochemical sequence that leads to atherosclerosis, plaque rupture, and eventually acute coronary syndromes. There is clinical and experimental evidence that ACE inhibition improves the life and death cycle of the endothelium. By restoring the bradykinin/angiotensin II balance, ACE inhibition reduces the rate of endothelial apoptosis and experimental results suggest that ACE inhibition can also improve the production and mobilization of endothelial progenitor cells from bone marrow. We report our experience in this context with perindopril. PMID- 20577900 TI - Sympathetic-parasympathetic interaction in health and disease: abnormalities and relevance in heart failure. AB - Sympathetic-parasympathetic interaction plays a major role in the evolution and outcome of many cardiovascular disorders. Nonetheless, a thorough understanding of this relationship and of its potential implications for prognosis and management still escapes many cardiologists. This article reviews the background of sympathetic-parasympathetic interactions focusing on the best direct evidence available, namely direct neural recordings of the activity of single vagal and sympathetic fibers directed to the heart. It examines indirect but highly reliable markers of this interaction as they can be studied in the clinical setting of ischemic heart disease and of heart failure, focusing primarily on the experimental and clinical studies of baroreflex sensitivity. It concludes by drawing inferences likely to lead to a novel approach to the management of heart failure, resulting from the knowledge gained about the vagal control of the heart and based on electrical vagal stimulation. PMID- 20577899 TI - Protective effects of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via antioxidant mechanisms and Ca(2+) antagonism. AB - Preclinical and clinical investigations have shown hippocampal neuronal atrophy and destruction were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Paeoniflorin, a monoterpene glycoside, has been reported to display antidepressant-like effects in animal models of behavioral despair. The present study aimed to examine the protective effect of paeoniflorin on glutamate-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with paeoniflorin elevated cell viability, inhibited apoptosis, decreased levels of intracellular reactive oxygen species and malondialdehyde, and enhanced activity of superoxide dismutase in glutamate-treated PC12 cells. Pretreatment with paeoniflorin also reversed the increased intracellular Ca(2+) concentration and the reduced Calbindin-D28K mRNA level caused by glutamate in PC12 cells. The results suggest that paeoniflorin exerts a neuroprotective effect on glutamate induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and Ca(2+) overload. This neuroprotective effect may be one of the action pathways accounting for the in vivo antidepressant activity of paeoniflorin. PMID- 20577902 TI - Photosynthesis online. AB - Online access to the Internet and the World Wide Web have become important for public awareness and for educating the world's population, including its political leaders, students, researchers, teachers, and ordinary citizens seeking information. Relevant information on photosynthesis-related Web sites and other online locations is grouped into several categories: (1) group sites, (2) sites by subject, (3) individual researcher's sites, (4) sites for educators and students, and (5) other useful sites. PMID- 20577901 TI - Methods of assessing vagus nerve activity and reflexes. AB - The methods used to assess cardiac parasympathetic (cardiovagal) activity and its effects on the heart in both humans and animal models are reviewed. Heart rate (HR)-based methods include measurements of the HR response to blockade of muscarinic cholinergic receptors (parasympathetic tone), beat-to-beat HR variability (HRV) (parasympathetic modulation), rate of post-exercise HR recovery (parasympathetic reactivation), and reflex-mediated changes in HR evoked by activation or inhibition of sensory (afferent) nerves. Sources of excitatory afferent input that increase cardiovagal activity and decrease HR include baroreceptors, chemoreceptors, trigeminal receptors, and subsets of cardiopulmonary receptors with vagal afferents. Sources of inhibitory afferent input include pulmonary stretch receptors with vagal afferents and subsets of visceral and somatic receptors with spinal afferents. The different methods used to assess cardiovagal control of the heart engage different mechanisms, and therefore provide unique and complementary insights into underlying physiology and pathophysiology. In addition, techniques for direct recording of cardiovagal nerve activity in animals; the use of decerebrate and in vitro preparations that avoid confounding effects of anesthesia; cardiovagal control of cardiac conduction, contractility, and refractoriness; and noncholinergic mechanisms are described. Advantages and limitations of the various methods are addressed, and future directions are proposed. PMID- 20577903 TI - Mandatory fortification of the food supply with cobalamin: an idea whose time has not yet come. AB - The success of folic acid fortification has generated consideration of similar fortification with cobalamin for its own sake but more so to mitigate possible neurologic risks from increased folate intake by cobalamin-deficient persons. However, the folate model itself, the success of which was predicted by successful clinical trials and the known favorable facts of high folic acid bioavailability and the infrequency of folate malabsorption, may not apply to cobalamin fortification. Cobalamin bioavailability is more restricted than folic acid and is unfortunately poorest in persons deficient in cobalamin. Moreover, clinical trials to demonstrate actual health benefits of relevant oral doses have not yet been done in persons with mild subclinical deficiency, who are the only practical targets of cobalamin fortification because >94% of persons with clinically overt cobalamin deficiency have severe malabsorption and therefore cannot respond to normal fortification doses. However, it is only in the severely malabsorptive disorders, such as pernicious anemia, not subclinical deficiency, that neurologic deterioration following folic acid therapy has been described to date. It is still unknown whether mild deficiency states, which usually arise from normal absorption or only food-bound cobalamin malabsorption, have real health consequences or how often they progress to overt clinical cobalamin deficiency. Reports of cognitive or other risks in the common subclinical deficiency state, although worrisome, have been inconsistent. Moreover, their observational nature proved neither causative connections nor documented health benefits. Extensive work, especially randomized clinical trials, must be done before mandatory dietary intervention on a national scale can be justified. PMID- 20577904 TI - Present and future of antisense therapy for splicing modulation in inherited metabolic disease. AB - The number of mutations identified deep in introns which activate or create novel splice sites resulting in pathogenic pseudoexon inclusion in mRNA continues to grow for inherited metabolic disease (IMD) and other human genetic diseases. A common characteristic is that the native splice sites remain intact thus retaining the potential for normal splicing. Antisense oligonucleotides (AO) have been shown to modulate the splicing pattern by steric hindrance of the recognition and binding of the splicing apparatus to the selected sequences. In the case of pseudoexons, AO force the use of the natural splice sites, recovering normally spliced transcripts encoding functional protein. This review summarizes the present knowledge of antisense splicing modulation as a molecular therapy approach for pseudoexon-activating mutations, with a focus in IMD. Although the feasibility of treatment for patients with IMD has yet to be proven, it appears to be clinically promising, as positive results have been reported in cellular and animal models of disease, and antisense therapy for splicing modulation is currently in the clinical trials phase for Duchenne muscular dystrophy patients. Here, we review the most recent advances in AO stability, targeting and delivery, and other issues to be considered for an effective treatment in the clinical setting. Although the number of patients who can be potentially treated is low for each IMD, it represents an excellent therapeutical option as a type of personalized molecular medicine which is especially relevant for diseases for which there is, to date, no efficient treatment. PMID- 20577905 TI - Acremonium species: a review of the etiological agents of emerging hyalohyphomycosis. AB - Unusual fungal agents that exist environmentally as saprophytes can often lead to opportunistic infections. Hyalohyphomycosis is a group of fungal infections caused by fungi characterized by hyaline septate hyphae and can infect both immunocompetent as well as immunocompromised patients. Many a times it becomes difficult to distinguish a pathogenic and a contaminant fungus, because many such agents can assume clinical significance depending on circumstances. Subcutaneous and invasive fungal infection due to the emerging hyalohyphomycotic fungus, Acremonium, has drawn the attention of clinicians and microbiologists, as a potential pathogen in patients with and without underlying risk factors. Generally considered to be minimally invasive in the past, genus Acremonium has been responsible for eumycotic mycetomas and focal infections in otherwise healthy individuals. It has also been increasingly implicated in systemic fungal diseases. The management with different antifungals in various clinical situations has been very conflicting and hence needs to be carefully evaluated. This overview is an endeavor to consolidate the available clinical infections due to Acremonium and the recommendations on treatment. PMID- 20577906 TI - Isolated sleep paralysis linked to impaired nocturnal sleep quality and health related quality of life in Chinese-Taiwanese patients with obstructive sleep apnea. AB - PURPOSE: Isolated sleep paralysis (ISP) is a rapid eye movement (REM) sleep parasomnia and has a special meaning in Chinese population. Worsening of obstructive sleep apnea (OSA) occurs especially during REM sleep. The relationship between ISP and OSA is unclear. The aim of this study was to investigate the impact of ISP on sleep and life quality in Chinese-Taiwanese OSA patients. METHODS: We recruited 107 OSA patients diagnosed by polysomnography (PSG) in Southern Taiwan. ISP was evaluated by self-reported sleep questionnaire. We used Chinese version of Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Short-Form 36 (SF36) to evaluate daytime sleepiness, nocturnal sleep quality, and health-related quality of life, respectively for OSA patients. Student's t-test was used to compare PSG parameters, ESS, PSQI, physical and mental component of SF-36 (P-SF36 and M-SF36) between OSA patients with and without ISP. Stepwise multiple regression was used to find out the factors independently associated with ESS, PSQI, P-SF36, and M-SF36. RESULTS: Forty-one of 107 patients (38.3%) had ISP. It showed no significant difference in PSG parameters between OSA patients with and without ISP. OSA patients with ISP had significantly higher ESS (P = 0.010), higher PSQI (P = 0.007), lower P-SF36 (P = 0.020), and lower M-SF36 (P = 0.001) than those without ISP. ISP was an independent factor associated with ESS (P = 0.017), PSQI (P = 0.001), and M-SF36 (P = 0.030) after adjusting for other confounding variables. CONCLUSIONS: ISP was independently associated with excessive daytime sleepiness, worse sleep quality, and impaired mental health-related quality of life in Chinese-Taiwanese OSA patients. PMID- 20577907 TI - Polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Liaodong Bay, Bohai Sea, China. AB - MATERIALS AND METHODS: The levels and possible sources of 16 polycyclic aromatic hydrocarbons (PAHs) were investigated in the surface sediments of Liaodong Bay, Bohai Sea, China. RESULTS: The sum of 16 PAHs (?PAH(16)) concentrations varied from 144.5 to 291.7 ng/g, with a mean value of 184.7 ng/g, indicating low PAH levels compared with reported values for other bays and rivers in China and developed countries. High concentrations of PAHs were observed in the Luan River Estuary and in the vicinity of Qinhuangdao, implying that sewage from the Luan River and shipping activities are important sources of PAHs in Liaodong Bay. CONCLUSION: An ecological risk assessment of PAHs, based on the effect range-low quotients, indicated that adverse biological effects caused by acenaphthene occasionally may take place in the sediments of Liaodong Bay. PAH source identification suggested that PAHs in most sediments were mainly from incomplete combustion of grass, wood, and coal. At other stations near the Luan River Estuary, both petrogenic and pyrogenic inputs were significant, and the petroleum derived PAHs were mainly from shipping activities and discharge of pollutants via rivers. PMID- 20577908 TI - Differentiation of normal and neoplastic bone tissue in dynamic gadolinium enhanced magnetic resonance imaging: validation of a semiautomated technique. AB - PURPOSE: This study was undertaken to clinically validate the accuracy of a semiautomated software tool for analysing the enhancement curve in focal malignant bone lesions. MATERIALS AND METHODS: Twenty-three patients affected by cancer with malignant focal bone lesions underwent dynamic gadolinium-enhanced magnetic resonance (MR) imaging using the following protocol: T1-weighted turbo spin-echo sequences (time to repeat [TR] 600 ms, time to echo [TE] 8.6 ms, field of view [FOV] 40x40 cm) before and after intravenous injection of gadolinium containing contrast agent. Image postprocessing was performed using the software DyCoH. Each region of interest (5x5 pixels), drawn to include the area of the lesion with the highest values of the area under the curve map, was analysed to obtain time-intensity curves and relative perfusion parameters: time to peak (TTP), peak intensity (PI), slope (60-s slope), intensity at 60 s after contrast agent injection (60-s I) and final intensity (FI). RESULTS: Data were obtained by analysing 86 malignant lesions and 86 apparently normal bone regions. PI, 60-s slope, 60-s I and FI were significantly different between neoplastic and apparently normal (p<0.001) samples. Sensitivity, specificity and accuracy were, respectively, 94%, 93% and 94% at a PI threshold of 100 (signal-to-noise ratio), with positive and negative predictive values of 93% and 94%. At a threshold value of 0.85 for 60-s slope, sensitivity and specificity values were both 91%. CONCLUSIONS: The semiautomated technique we report appears to be accurate for identifying neoplastic tissue and for mapping perfusion parameters, with the added value of a consistent measurement of perfusion parameters on colour-coded maps. PMID- 20577909 TI - Incidence of new fractures in women with osteoporosis-induced vertebral fractures detected on routine lateral chest radiographs. AB - PURPOSE: Vertebral fractures represent one of the major complications of osteopororis. Diagnosis is followed by a pharmacological, interventional or surgical treatment. Up to day there are non practice guidelines for a screening evaluation of bone fractures in elderly and most of the fractures remain undiagnosed. We prospectively evaluated the prevalence of vertebral fractures on chest X-rays to determine the diagnostic and prognostic roles of chest X-ray in predicting new bone fractures 2 years after the initial radiogram. MATERIALS AND METHODS: Between March 2004 and October 2005, 4,045 women underwent chest X-ray in our radiology department for any indication. We identified 166 women with the presence of at least one vertebral fracture. A questionnaire was administered to these women to collect information about diagnosis of osteoporosis, history of malignancy, systemic diseases, osteoporosis-inducing drugs and pharmacological, radiological or surgical treatment received. RESULTS: Out of the 166 women (age 73+/-10.5 years) with vertebral fractures, we interviewed 101 women; 13 had died and 52 were not found. Most of the patients were on menopause (97.1%, 98/101) with an average age of menopause of 48,2 years (+/-6 years). Among the patients on menopause, 15,8% (16/101) had undergone hysterectomy. All patients received a diagnosis of osteoporosis, which was reached with a chest X-ray report in 23.7% (24/101) of cases. A new skeletal fracture occurred in 20.5% (5/27) of patients receiving treatment against a frequency of 20.8% (16/74) in patients without treatment. No statistical difference was found between the groups (p = 0.374). CONCLUSIONS: Inadequate treatment may explain the lack of a substantial difference in new fracture risk between treated and untreated patients. For these reason we discuss about the evaluation of an adeguate therapeutic approaches in prevention of osteoporosis-induced fractures. PMID- 20577910 TI - Clinical features and independent prognostic factors for acute bacterial meningitis in adults. AB - BACKGROUND: Clinical recognition of acute bacterial meningitis (ABM) and its early prognostication would guide the degree of intensive treatment required. We aimed to study the clinical features and factors associated with death in patients with community acquired ABM. METHODS: Adult patients with clinically suspected community acquired ABM (CAABM) were studied between July 2004 to September 2008 (retrospective and prospective). Detailed history, clinical examination, cerebrospinal fluid (CSF) analysis, and laboratory investigations were performed and noted. The complications with which the patient presented or developed during hospital course were also noted. The outcome noted was at the time of discharge. RESULTS: In multivariate logistic regression, independent factors associated with death were rural area of residence, presentation after >24 h, total leukocyte count (TLC) of <15000, CSF neutrophils <75%, low GCS at the time of admission, and a high creatinine level. CONCLUSIONS: In the present study, most of the factors predicting death were identified at the time of admission. Identification of these factors could help prioritizing patients needing intensive care facilities, especially in resource poor setting. PMID- 20577911 TI - Death by black powder revolver: a case report. AB - Deaths resulting from the use of black powder handguns are relatively uncommon compared to other firearms. We report the case of a 48 year-old woman who sustained a lethal gunshot wound to the face from a black powder revolver. Autopsy revealed extensive soot and powder deposition around the entrance wound between the right eye and nose with perforation of the skull and brain. The exit wound also contained evidence of soot. Discussion of this characteristic pattern of discharge deposition from black powder weapons is presented. PMID- 20577912 TI - Alginate-chitosan-PLGA composite microspheres enabling single-shot hepatitis B vaccination. AB - Hepatitis B vaccination typically requires a multi-dose administration protocol over a course of 3-6 months. Aiming at developing a single-shot formulation for hepatitis B vaccine (hepatitis B surface antigen (HBsAg)), a novel vaccine delivery system, the composite microspheres of alginate-chitosan-poly(lactic-co glycolic acid) (PLGA), was synthesized by a two-step preparation. The composite microspheres showed distinct advantages over the conventional PLGA microspheres in aspects of the high loading capacity and the elimination of lyophilizing process. The loading capacity of the composite microspheres was about seven times higher than those in the conventional PLGA microspheres, due to the protein friendly microenvironment created by the hydrophilic alginate-chitosan cores of the composite microspheres. This vaccine delivery system was shown to be able to induce robust immune responses by single injection and display no significant difference in HBsAg-specific antibody levels compared to the double-injection method. PMID- 20577914 TI - [A prospective randomized control trial of the approach for laparoscopic right hemi-colectomy:medial-to-lateral versus lateral-to-medial]. AB - OBJECTIVE: To compare the medial-to-lateral approach with the lateral-to-medial approach in laparoscopic right hemi-colectomy for right colon cancer. METHODS: A prospective randomized controlled trial was performed in the Fujian provincial tumor hospital between January 2007 and July 2009. Forty-eight cases with right colon cancer were randomly divided into two groups:medial-to-lateral laparoscopic right hemi-colectomy group(group M) and lateral-to-medial laparoscopic right hemi colectomy group(group L). Primary outcome(operative time) and secondary outcomes (estimated blood loss, intra-operative complication, post-operative complication, number of lymph node retrieval, hospital stay) were compared between two groups. RESULTS: Operative time was(122.5+/-25.8) min in group M and (162.9+/-30.9) min in Group L (P=0.01). Estimated blood loss was(55.8+/-36.2) ml in group M and (104.6+/-58.2) ml in group L(P=0.01). There were no significant differences between the two groups in intra-operative complications(4.2% vs 8.3%, P=1.00), post-operative complications (8.3% vs 16.7%, P=0.66), number of lymph node retrieval (17.4+/-3.2 vs 17.8+/-3.4, P=0.67), and hospital stay[(7.8+/-2.2) d vs (8.0+/-3.6) d, P=0.81]. CONCLUSION: The medial-to-lateral approach reduces operative time and blood loss in laparoscopic right hemi-colectomy as compared with the lateral-to-medial approach. PMID- 20577913 TI - The relationship of health numeracy to cancer screening. AB - Health numeracy is associated with increased understanding of cancer risk reduction information and improved control of chronic disease. A cross-sectional survey was conducted among a primary care population to evaluate the effect of health numeracy on breast, cervical, and colorectal cancer screening. No association was found between health numeracy and cancer screening. However, at a baseline screening rate of 85%, increased knowledge (RR 1.06, 95% CI 1.02-1.08) and decreased perceived barriers (RR 0.93, 95% CI 0.92-0.95) were associated with increased screening rates. In conclusion, health numeracy was not predictive of cancer screening among a primary care population. PMID- 20577915 TI - [Effect of colonoscopy combined with placement of metallic clips on selecting colonic surgery incision]. AB - OBJECTIVE: To evaluate the accuracy and value of the placement of metallic clips during colonoscopy in the localization of colorectal cancer and incision selection. METHODS: A total of 30 patients received metallic clip placement by colonoscopy before operation. Abdominal plain film (supine and upright position) was taken and incision was determined by the projection of clips on the abdominal wall. RESULTS: The inaccuracy rate of localization by colonoscopy was 30%(9/30). Colonoscopy combined with the placement of metallic clips achieved an accurate incision rate of 100% (30/30). CONCLUSIONS: There is a considerable rate of inaccuracy for localization in colonic cancer by colonoscopy. Colonoscopy combined with placement of metallic clips should be considered in order to select a reasonable incision. PMID- 20577916 TI - [Comparative study of recurrent colon cancer and recurrent rectal cancer after radical resection]. AB - OBJECTIVE: To explore the difference in tumor biological behaviors and prognosis between recurrent colon cancer and recurrent rectal cancer after radical operation. METHODS: Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal cancers, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer. RESULTS: Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer(P<0.05). Colon cancer recurred earlier than rectal cancer after radical surgery with the median time to recurrence being 14.0 months and 21.5 months, respectively(P=0.028). The difference in multiple sites recurrence was also found between colon(n=16, 44.4%) and rectal cancer(n=65, 67.7%)(P=0.014). The 3-year survival rate of recurrent rectal cancer was better than that of colon cancer (24.8% vs 15.6%, P=0.026). CONCLUSION: There are some differences in tumor biological behaviors between colon and rectal cancer, and the prognosis of rectal cancer with recurrence is better than that of colon cancer. PMID- 20577917 TI - [Analysis of clinical characteristics and prognosis of perineural invasion in patients with gastric carcinoma]. AB - OBJECTIVE: To investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma. METHODS: A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied. RESULTS: PNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI positive patients(28.6 months) was significantly shorter than that of PNI negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006). CONCLUSIONS: PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor. PMID- 20577918 TI - [Surgical treatment for 140 patients with gastric stromal tumors]. AB - OBJECTIVE: To analyze the outcome of the patients with gastric gastrointestinal stromal tumor(GIST) after surgical treatment and identify the associated risk factors. METHODS: Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis. RESULTS: The overall survival rates of 1-, 3-, 5-year were 96.8%, 86.7% and 79.3%, respectively. The survival rates of 1 , 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P<0.05). Gender, preoperative metastasis, tumor size,pathology type,karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis(P<0.05). CONCLUSION: Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment. PMID- 20577919 TI - [Risk factors for postoperative pancreatic leakage after D(2) resection of gastric cancer]. AB - OBJECTIVE: To investigate the incidence of pancreatic fistula following D(2) gastrectomy and associated risk factors. METHODS: A total of 132 consecutive cases of gastric cancer underwent D(2) gastrectomy between Jul 1, 2009 and Dec 2009. Amylase concentration of the drainage fluid and serum amylase concentration were tested on day 1, 4, 7 after operation. Univariate analyses were performed to evaluate the significance of various covariates as risk factors for the pancreatic fistula-related complications. RESULTS: The incidence of pancreatic fistula was 17.4%. None of the following factors including age, gender, tumor location, tumor stage, N stage, range of resection, fistula output, and serum amylase were associated with pancreatic fistula. CONCLUSION: The incidence of pancreatic fistula following D(2) gastrectomy is high. Drainage tube is necessary to prevent serious complications. PMID- 20577920 TI - [Comparison of clinical manifestation and severity between hospital-based American and Chinese patients with colorectal Crohn disease]. AB - OBJECTIVE: To evaluate the differences in clinicopathological characteristics and severity between American and Chinese patients with colorectal Crohn disease(CD). METHODS: Between March 1985 and September 2004, 68 patients with colorectal CD in Cleveland Clinic Florida (America) and 85 patients with colorectal CD in the 301 Hospital(China) were enrolled in the study. Data of two groups,including demographics, clinical characteristics, extraintestinal manifestations, presenting symptoms, location and pathological characteristics,were compared. RESULTS: 60.3% of American patients and 36.5% of Chinese patients were female(P=0.003). 11.8% of American patients and 1.2% of Chinese patients had a family history of CD(P=0.016). American patients had a significantly higher rate of extraintestinal disease (39.7% vs 20.0%), abscess(19.0% vs 0), and anorectal fistulas(51.5% vs 0). American patients had significantly more extensive disease than Chinese patients(pancolitis: 44.1% vs 4.7%, P<0.01). American patients had a significantly higher rate of disease involving the ascending colon, transverse colon, descending colon, sigmoid colon, anorectal area compared with Chinese patients(all P<0.05). CONCLUSIONS: American patients with colorectal Crohn disease seem to have a female predominance, a higher rate of CD family history, to involve the distal intestinal tract more often, and have more severe clinical manifestation and pathological process, as compared with Chinese patients. PMID- 20577921 TI - [Application of Altemeier procedure in the emergent management of acute incarcerated rectal prolapse]. AB - OBJECTIVE: To evaluate the perineal rectosigmoidectomy(Altemeier procedure) in the emergent management of acute incarcerated rectal prolapse. METHODS: Clinical and follow-up data of 9 patients with acute incarcerated rectal prolapse undergone Altemeier procedure were retrospectively analyzed. RESULTS: The mean operation time was 1.7 (range 1.0-1.5) hours. The mean total blood loss during surgery was 109 (50-200) ml. The mean time to the first bowel movements was 2.8(1 6) days after surgery. The hospital stay was 5.3(3-10) days. There were no postoperative complications such as anastomotic leakage, intra-abdominal infection, or urogenital dysfunction. One patient developed thrombosis in the mesorectum and one patient had symptoms of anal discomfort. After a mean follow up of 3.5(5 months-6.5 years) years, no patient had recurrent prolapse. Six months after operation, anal function was Kirwan grade I( in 8 cases and grade II( in 1 case. All the patients were satisfied with the result. CONCLUSION: Altemeier procedure can result in good postoperative anal function when treating incarcerated rectal prolapse, which should be the first choice in emergency treatment. PMID- 20577922 TI - [Analysis of surgical treatment for severe ulcerative colitis]. AB - OBJECTIVE: To evaluate the role of different procedures in the treatment of severe ulcerative colitis (UC) requiring colectomy. METHODS: A total of 29 UC inpatients who underwent colectomy at the West China Hospital between January 1996 and December 2008 were included in this study. Except two cases who underwent partial colectomy, patients were divided into total colectomy group (TC group, n=7) and total proctocolectomy group (TPC group, n=20), meanwhile divided into ileal pouch-anal anastomosis (IPAA, n=8) group, straight end-to-end anastomosis (ileoanal or ileorectal and ileostomy) group (n=14)and ileostomy group (n=5). Quality of life (QOL) was assessed using the Cleveland Global Quality of Life (CGQL) instrument. RESULTS: The complication rate was 60.0% in TPC group and 57.1% in TC group (P>0.05). The recurrence rate was 15.0% in TPC group and 57.1% in TC group (P<0.05). The complication rate was 6/8 in IPAA group and 50.0% (7/14) in straight end-to-end anastomosis group (P>0.05). The frequency of daily bowel movements in IPAA group was significantly lower than that in straight end-to-end anastomosis group at 1 year after the surgery (5.6+/-1.7 versus 9.1+/-2.9, P<0.05). QOL was significantly improved postoperatively for all the patients(P<0.01). Patients who underwent IPAA had a better QOL than those of straight end-to-end anastomosis group (P>0.05). CONCLUSIONS: TPC-IPAA is the ideal procedure of severe UC with acceptable complication rate, satisfactory quality of life and functional outcome. PMID- 20577923 TI - [Effects of perioperative total parenteral nutrition support on cyclin D1 expression, recurrence and metastasis of colorectal cancer cells]. AB - OBJECTIVE: To evaluate the effects of perioperative total parenteral nutrition on cyclin D1, recurrence and metastasis of colorectal cancer cells. METHODS: A total of 120 patients with colorectal carcinoma were randomly divided into two groups, namely group A(total parenteral nutrition, TPN,60 cases) and group B(non total parenteral nutrition, NTPN, 60 cases). In group A, the patients were given with TPN(including glucose, intralipid, amino acid, and vitamins, etc.) for 10 days perioperation (7 days preoperatively and 3 days postoperatively). In group B, the patients did not receive any nutrition support perioperative nutrition support. The samples were obtained by colonoscopy preoperatively or during operation. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique,expression of proliferating cell nuclear antigen (PCNA) by immunohistochemical staining, and the expression of cyclin D1 by in situ hybridization. The apoptotic index (AI), the proliferating index (PI), and the expression of cyclin D1 were calculated perioperatively and postoperatively. RESULTS: After perioperative nutrition support, the expression rates of cyclin D1, PI and AI in group A and group B were (35.23+/-5.12)% and (37.53+/-5.31)%, (7.21+/-2.56)% and (8.75+/-3.84)%, (53.45+/-7.74)% and (56.74+/-8.02)% respectively. There were no significant difference of PI, AI and the expression of cyclin D1(all P>0.05) between two groups. The 3-year recurrent rates in two groups were 16.7% and 15.0%( P>0.05). CONCLUSION: Perioperative TPN can not promote proliferation and apoptosis of carcinoma cells, and has no significant impact on the expression of cyclin D1, recurrence or metastasis of colorectal cancer. PMID- 20577924 TI - [Establishment of a nude mouse model of highly metastatic gastric lymphoma constructed with orthotopic transplantation of surgical specimen]. AB - OBJECTIVE: To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. METHODS: A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. RESULTS: An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. CONCLUSIONS: An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma. PMID- 20577925 TI - [Demethylation of the gamma-synuclein gene CpG island in colorectal cancer and its clinical significance]. AB - OBJECTIVE: To explore the relationship between gamma-synuclein gene expression and CpG island demethylation in colorectal cancer(CRC), and the relationship between the demethylation and clinicopathological factors of CRC. METHODS: The expression of gamma-synuclein mRNA was examined in 30 pairs of tumor tissues and tumor-matched non-neoplastic adjacent tissues(NNAT) by RT-PCR. CRC cell lines including COLO205, LoVo, and SW480 were used and treated with a demethylating agent, 5-aza-2'-deoxycytidine(5-aza-C). Before and after the treatment, the expression of gamma-synuclein mRNA in the cells was determined by RT-PCR, and bisulfite sequencing PCR was also used to analyze methylation status of CpG island. The methylation status of gamma-synuclein was then examined in 67 CRC samples and 30 NNAT samples by nested methylation-specific PCR (NMSP) and real time methylation-specific PCR(real-time MSP). The relationship between the demethylation of gamma-synuclein in CRC and clinicopathological factors was analyzed. RESULTS: The mean gamma-synuclein mRNA expression was 0.66+/-0.34 in CRC samples, which was much higher than 0.45+/-0.26 in NNAT samples(P=0.011). 5 aza-C could induce expression and demethylation of gamma-synuclein in COLO205, LoVo and SW480 cells. gamma-Synuclein gene was demethylated in 80.0%(24/30) of the CRC samples and 50.0%(15/30) of the NNAT samples. The demethylated status of gamma-synuclein was much higher in CRC samples than that in NNAT samples(P=0.030), and was significantly correlated with clinical stage, lymph node involvement, and distant metastasis of CRC(P<0.05). CONCLUSION: The upregulation of gamma-synuclein expression in CRC is primarily attributed to the demethylation of CpG island, which may be used as a marker for prognosis. PMID- 20577926 TI - [Expression and significance of aquaporin 4 in the colonic mucosa of patients with slow transit constipation]. AB - OBJECTIVE: To explore the relationship between the expression of aquaporin 4 (AQP4) and slow transit constipation(STC). METHODS: The expression of AQP4 in the ascending colon mucosa of 45 patients with STC was detected by immunohistochemistry. The transit time of stool was measured with barium sulfate suspensions. Stool was classified using Bristol stool chart. The difference between the pre- and post-operation groups was analyzed. RESULTS: Of 45 STC patients, 36 had high AQP4 expression (high expression group) and 9 had low AQP4 expression(low expression group). Preoperatively 30(83.3%) patients in the high expression group and 3(3/9) patients in the low expression group presented dry and hard stool (type I( or II()(P<0.01). Postoperatively, stool pattern was improved in all the patients of high expression group. One patient in low expression group still presented dry and hard stool(P<0.01). Preoperatively the transit time was(127.3+/-28.2) h in high expression group and (64.2+/-12.9) h in low expression group(P<0.01). Postoperatively, the transit time was (17.3+/-7.0) h in high expression group and (28.0+/-12.6) h in low expression groups(P<0.01). CONCLUSION: High expression of AQP4 accelerates the water absorption in colon mucosa and may be one of the crucial events in the development of STC. PMID- 20577928 TI - Preface. Neurologic complications of cancer. PMID- 20577929 TI - Brain metastases. AB - Approximately 10% of patients with cancer develop brain metastases. Some evidence indicates that as techniques for treating systemic tumors improve, the incidence of brain metastases, sequestered as they are behind the blood-brain barrier, is increasing. Although usually appearing late in the course of the disease, a brain metastasis may cause the initial symptoms, before the primary cancer has been identified. The diagnostic and therapeutic approach depends on the number and location of brain lesions and the stage of the cancer. Patients with brain metastases are rarely cured. However, appropriate treatment can improve both the quality and duration of the patient's life. Treatment must be directed not only at the brain metastasis (definitive care), but also at a multitude of other symptoms that plague patients with brain metastases (supportive care). Judicious selection of pharmacologic agents and nonpharmacologic techniques can effectively treat many serious symptoms in patients with brain metastases, but injudicious selection of pharmacologic agents may have side effects and make the patient's quality of life worse. The authors review some aspects of both definitive and supportive care with particular attention to the side effects of some commonly used pharmacologic agents. PMID- 20577930 TI - Leptomeningeal metastasis. AB - Leptomeningeal metastasis occurs in ~5% of all patients with cancer and is the third most common metastatic complication of the central nervous system. Staging of leptomeningeal metastasis includes contrast-enhanced brain and spine magnetic resonance imaging and radionuclide cerebrospinal fluid (CSF) flow study. Treatment, when clinically indicated, often requires administration of involved field radiotherapy to bulky or symptomatic disease sites as well as intra-CSF and systemic chemotherapy. The use of high-dose systemic therapy may benefit selected patients with breast- or lymphoma-related leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra-CSF drug therapy primarily utilizes one of three chemotherapeutic agents (e.g., methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Beginning to be utilized are novel intra-CSF agents, such as the targeted monoclonal antibodies rituximab (anti-CD20 for B cell lymphoma-related leptomeningeal metastasis) and trastuzumab (anti-Her2/neu for breast cancer-related leptomeningeal metastasis). Although treatment of leptomeningeal metastasis is palliative with median patient survival of 2 to 3 months, treatment may afford stabilization and protection from further neurologic deterioration in patients with leptomeningeal metastasis. PMID- 20577931 TI - Metastatic epidural spinal cord compression. AB - Metastatic epidural spinal cord compression is a debilitating consequence of multiple cancer types. Early diagnosis and treatment are imperative for improving functional outcome. The authors review the epidemiology, pathophysiology, clinical features, and diagnostic evaluation of metastatic epidural spinal cord compression. Special attention will be given to the supportive and definitive treatments available for management, and new therapeutic interventions, such as radiosurgery, will be briefly discussed as well. PMID- 20577932 TI - Neurologic manifestations of neoplastic and radiation-induced plexopathies. AB - Metastatic plexopathy is often a disabling accompaniment of advanced systemic cancer, and may involve any of the peripheral nerve plexuses. Brachial plexopathy most commonly occurs in carcinoma of the breast and lung; lumbosacral plexopathy is most common with colorectal and gynecologic tumors, sarcomas, and lymphomas. Neoplastic plexopathy is often characterized initially by severe, unrelenting pain followed by development of weakness and focal sensory disturbances. In previously treated patients, the main differential diagnostic consideration is radiation-induced plexopathy, which can be difficult to distinguish from tumor plexopathy. Diagnosis is usually made following an analysis of the clinical, neuroimaging, and electrophysiologic features. Treatment of metastatic plexopathy has included surgical resection of tumor in selected cases, radiotherapy to the plexus, systemic chemotherapy, interventional pain management procedures, and symptomatic treatment. These measures often offer temporary (months) relief or improvement. Physicians treating these patients should focus on effective management of pain and prevention of complications of immobility produced by the neuromuscular dysfunction. PMID- 20577933 TI - Treatment and prevention of secondary CNS lymphoma. AB - Central nervous system (CNS) involvement in non-Hodgkin lymphoma is a serious, potentially preventable complication that can occur in 5 to 10% of patients. Its occurrence is directly correlated with pathologic aggressiveness and ranges from less than 3% in the indolent, less-aggressive histologies to as high as 50% in the very aggressive ones such as Burkitt lymphoma. Aggressive treatment once detected can improve neurologic outcome, but because it is often associated with contemporaneous systemic relapse, is rarely associated with long-term survival. Preventing its occurrence, therefore, remains an important goal of initial treatment. Despite there being some suggestive evidence that the addition of systemic rituximab and several intracerebrospinal fluid chemotherapy regimens may have decreased the incidence of CNS involvement, both optimal selection of those patients who should receive prophylaxis as well as the best prophylactic regimen remain active areas of investigation. PMID- 20577934 TI - Neurotoxicity of cancer chemotherapy. AB - Neurologic dysfunction is a common side effect of many chemotherapy drugs. For several agents, neurotoxicity is common, severe, and can be dose-limiting. As the list of newer chemotherapy agents and systemic "targeted therapies" grows, so does the number and variety of potential neurotoxicities. This is a review of the clinical features of chemotherapy-induced syndromes involving the central and peripheral nervous systems. PMID- 20577935 TI - Neurologic complications of hematopoietic cell transplantation. AB - Hematopoietic cell transplantation (HCT) involves the intravenous infusion of hematopoietic progenitor cells from an HLA-matched donor (allogeneic) or from the patient (autologous). Prior to HCT, the recipient is prepared (conditioning) with high-dose chemotherapy or radiotherapy (or both) to destroy defective bone marrow or residual cancer cells. After allogeneic HCT, there is the need for chronic immunosuppression to prevent graft rejection and graft-versus-host disease (GVHD). The frequency and type of neurologic complications depends on the type of HCT, the underlying disease, and the case ascertainment. In this review, the neurologic complications are presented according to the stage of HCT that they are most likely to occur: (1) conditioning-drug-related encephalopathies and seizures or complications secondary to medical procedures; (2) bone marrow depletion-metabolic and drug-related encephalopathies and seizures, septic cerebral infarctions, and hemorrhages; (3) chronic immunosuppression-infections by viruses and opportunistic organisms; and (4) late events-central nervous system (CNS) relapses of the original disease, neurologic complications of GVHD, and second neoplasms. PMID- 20577936 TI - Central nervous system infections in cancer patients. AB - With improved treatments, patients with many types of cancer survive longer. However, both the acute adverse effects of more intensive therapies and the risks of chronic immunosuppression have led to a diverse and evolving spectrum of central nervous system (CNS) infections. The presentation and course of CNS infections in cancer patients may be different from those in patients without cancer, complicating and delaying accurate diagnosis. New syndromes related both to the underlying malignancies and to their treatment continue to emerge. Noninfectious disorders such as adverse drug effects, vascular lesions, and radiation effects can mimic CNS infections. The two major clinical presentations of CNS infections are meningoencephalitic syndromes and focal deficits due to mass lesions. The range of pathogens can be narrowed by considering the type of immune deficit present, local nosocomial trends, and the specific vulnerabilities created by the underlying disease and treatment regimen. Patients undergoing neurosurgical procedures and those receiving hematopoietic cell transplants (HCT) account for the majority of cancer patients with CNS infections. Significant recent changes reviewed here include evolving patterns of bacterial meningitis, current treatment recommendations for fungal infections, special infectious risks associated with immunomodulatory therapies, and neuroimaging techniques to distinguish infection from other intracranial processes. PMID- 20577937 TI - Cerebrovascular complications in patients with cancer. AB - Stroke in the cancer patient is often caused by disorders of coagulation that are induced by the cancer, by cancer metastatic to the central nervous system, or by coagulation disorders or vascular injury due to cancer therapy. Nonbacterial thrombotic endocarditis in association with diffuse thrombosis of cerebral vessels is often the cause of cerebral infarction. Venous occlusion is most common in leukemic patients, but can also result from growth of solid tumor in the adjacent skull or dura. Chemotherapy administration is associated with a small risk of cerebral arterial or venous thrombosis. Radiation that is administered to the neck can result in delayed carotid atherosclerosis. Tumor embolization to the brain is a rare cause of stroke. Fungal septic cerebral emboli occur most commonly in leukemic patients who have undergone bone marrow transplantation. Hemorrhages occur in the brain parenchyma or the subdural and subarachnoid spaces and are most commonly caused by acute disseminated intravascular coagulation or metastatic tumor. Hemolysis from chemotherapy administration is a rare cause of brain hemorrhage. Careful clinical assessment, neuroimaging studies, measurement of coagulation function, and echocardiography are the most useful modalities to identify the cause of stroke. PMID- 20577938 TI - Update on paraneoplastic and autoimmune disorders of the central nervous system. AB - Although the discovery of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurologic disorders, the recognition and treatment of these disorders remain a challenge. Some antibodies are more syndrome-specific than others, and some syndromes suggest a paraneoplastic etiology more frequently than others. Because some antineuronal antibodies may occur in cancer patients without paraneoplastic neurologic disorders, their detection does not necessarily imply that a neurologic disorder is paraneoplastic. Moreover, there is an emerging group of encephalitides that appear to be mediated by antibodies against cell surface or synaptic proteins, may occur with or without tumor association, and are responsive to treatment. This review analyzes the immune responses associated with paraneoplastic and nonparaneoplastic disorders of the central nervous system, and the main clinical features and response to treatment. PMID- 20577939 TI - [Quality management systems in radiology: implementation in hospital and radiology practice]. AB - The concept of quality and the principle of continuous quality improvement are implemented by quality management systems. Quality management systems surpass mere quality control. These systems account for patient and employee needs, the management style and the structure of an enterprise. Many of these quality management systems are used in the health care industry. Some of these systems and their form of application in radiology are introduced here. PMID- 20577940 TI - [Benign prevertebral edema as expression of retropharyngeal tendinitis--MRI image of a rare entity]. PMID- 20577941 TI - Contrast ultrasonography: necessity of linear data processing for the quantification of tumor vascularization. AB - PURPOSE: This study is intended to compare the value of uncompressed ultrasonic data, obtained after linear power detection of the ultrasonic radiofrequencies that we call linear data, with usual compressed video data for the quantification of tumor perfusion, particularly for monitoring antivascular therapy. MATERIALS AND METHODS: To form a clinically useful ultrasonic image, the detected power of the received signals (linear data) is compressed in a quasi-logarithmic fashion in order to match the limited dynamic range of the video monitor. The resulting reduced range of signals from an injected contrast agent may limit the sensitivity to changes in the time-intensity curves. Following a theoretical evaluation of the effects of compression on time-intensity curves and as an in vivo example, we measured at different times the effects of an antivascular drug administered to mice bearing melanoma tumors. The mean time-intensity curves within the tumors after bolus injection of a contrast agent were determined using both linear and video data. Linearized data was recovered using the inverse of the true scanner's compression law, which was experimentally determined. Three features were extracted from the time-intensity curves: peak intensity (PI), time to peak intensity (TPI) and area under the curve in the wash-in phase (AUC (wash in)). When contrast reached its maximum value, the coefficient of variation reflecting the heterogeneity of the intensity of contrast uptake within the tumor, was computed using both data sets. RESULTS: TPI was found to be similar with either data set (r = 0.98, p < 0.05, factor of 1.09). Linear PI and AUC (wash-in) had significantly earlier decreases after drug administration than video data (p = 0.015 and p = 0.03, respectively). The coefficient of variation was significantly lower when using video rather than linear data (p < 10 (-4)). CONCLUSION: In conclusion, the use of linear data is the only mathematically valid methodology for determining a tumor's time-intensity curve and, in practice, it allows earlier demonstration of responses to antivascular drugs. PMID- 20577942 TI - Microtubule-binding natural products for cancer therapy. AB - Natural products, especially microtubule-binding natural products, play important roles in the war against cancer. From the clinical use of vinblastine in 1961, paclitaxel in 1992, to ixabepilone in 2007, microtubule-binding natural products have continually contributed to the development of cancer therapy. The present review summarizes the development of representative microtubule-binding natural products including agents binding to the colchicine-binding site, the VINCA alkaloid-binding site, the taxane-binding site and other binding sites. Future directions for the development of new anticancer microtubule-binding natural products are discussed. Finding new formulations, new targets and new sources of microtubule-binding natural products may enable more members of this kind of agent to be introduced into the clinic for cancer therapy. PMID- 20577943 TI - Historic perspectives on Annonaceous acetogenins from the chemical bench to preclinical trials. AB - Studies on the Annonaceous acetogenins began after the first cytotoxic acetogenin, uvaricin, was isolated in 1982. This attractive finding made many medicinal and natural product chemists direct their efforts on the isolation and identification of these classes of compounds. As more Annonaceous acetogenins were isolated, more information about them was uncovered. From their structural identification to the total synthesis of natural product analogues and from cell based screening and molecular-based targeting to animal testing, the mechanisms of action of the Annonaceous acetogenins became clearer. The purpose of this review is to give an account of recent studies on this class of compounds and their analogues, which will aid us not only in clarifying how the Annonaceous acetogenins act but also in establishing principles for the further development of this class of compounds. PMID- 20577944 TI - Preventive effects of berberine on glucocorticoid-induced osteoporosis in rats. AB - Glucocorticoids are widely used to treat chronic diseases such as rheumatoid arthritis and asthma. However, long-term glucocorticoid therapy can result in serious side effects, such as osteoporosis. The present study investigated the preventive effects of berberine on glucocorticoid-induced osteoporosis in rats. Male Sprague Dawley rats were treated with vehicle, glucocorticoid, glucocorticoid and berberine, or glucocorticoid and calcium carbonate with vitamin D (3) for 12 weeks. The proximal tibiae of all rats were processed without decalcification for quantitative bone histomorphometry, and femur mechanical testing as well as bone mineral density (BMD) were analyzed. A significant decrease was found in the glucocorticoid-treated group compared with the control group in such indices as biomechanical quality, BMD, trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), mineral apposition rate (MAR), bone formation rate/total tissue area (BFR/TV), and bone formation rate/trabecular bone surface (BFR/BS). In addition, significantly increased trabecular separation (Tb.Sp), osteoclast number/trabecular bone volume (Oc.N/BV), and osteoclast surface/trabecular bone surface (Oc.S/BS) were observed in the glucocorticoid-treated group, compared with the control group. Berberine and calcium carbonate with vitamin D (3) prevented the decrease in biomechanical quality, BMD, BV/TV, Tb.N, Tb.Th, MAR, BFR/TV, and BFR/BS, as well as increased Tb.Sp, Oc.N/BV, and Oc.S/BS in glucocorticoid-induced osteoporotic rats. The present results suggest that berberine prevents glucocorticoid-induced osteoporosis by inhibiting bone resorption and improving bone formation. PMID- 20577945 TI - African descents are more sensitive than European descents to the antitumor compounds alpha-hederin and kalopanaxsaponin I. AB - alpha-Hederin, a natural triterpene saponin and its derivative kalopanaxsaponin I (ksI) exhibit cytotoxicity against various cancer cell lines and IN VIVO tumors. We studied the genetic variants contributing to the activity of these two anticancer compounds. Cell lines derived from 30 trios of European descent (Centre d'Etude du Polymorphisme Human, CEPH; CEU) and 30 trios of African descent (Yoruban, YRI) were used. Cytotoxicity was determined as inhibition of cell growth at increasing concentrations of alpha-hederin or ksI for 24 h. In comparison to the European, the Yoruban populations revealed a higher sensitivity to alpha-hederin and to ksI that can be attributed to several unique SNPs. These SNPs are located near 111 and 130 genes in the European and the Yoruban populations, respectively, raising the possibility that some of these genes contribute to the differential sensitivity to these compounds. PMID- 20577946 TI - Isolation and anti-inflammatory activity evaluation of triterpenoids and a monoterpenoid glycoside from Harpagophytum procumbens. AB - A new triterpenoid glycoside, designated harproside (1), and a new iridoid glycoside, named pagide (2), along with six known triterpenoids (3-8), were obtained from the tubers of Harpagophytum procumbens D. C. (devil's claw), and their structures were established through chemical methods and spectroscopic analyses. In an in vitro assay, the six triterpenoids showed anti-inflammatory activity. Compounds 3, 7, and 8 showed significant inhibitory activity against neutrophil respiratory burst stimulated by PMA, while compounds 4, 5, and 6 showed marginal inhibitory activity. PMID- 20577947 TI - Two new drimane sesquiterpenes, fudecadiones A and B, from the soil fungus Penicillium sp. BCC 17468. AB - Two new drimane sesquiterpenoids, fudecadione A and fudecadione B (1, 2), together with the known brefeldin A (3) and fulvic acid (4), were isolated from the soil fungus Penicillium sp. BCC 17468. Chemical structures were determined based on spectroscopic evidence including 1D and 2D NMR and mass spectral data. The proposed relative stereochemistry of fudecadiones A and B was based upon NOESY spectral data and chemical means. Compounds 1 and 4 exhibited anticancer activity against MCF-7, KB, and NCI-H187, with IC (50) values in the range of 5.05-45.43 ug/mL, while compound 2 was inactive against these tumor cells. Brefeldin (3) also displayed antimalarial activity against PLASMODIUM FALCIPARUM (K1, multidrug-resistant strain), with an IC (50) value of 1.12 ug/mL. PMID- 20577949 TI - [Prognostic Relevance of the Metastatic Localisation in Patients with Stage IV NSCLC - Results of a Prospective Epidemiological Study]. AB - Patients with non-small cell lung cancer (NSCLC) frequently suffer from stage IV disease at the time of presentation. Survival of these patients is disadvantageous although they may benefit from chemotherapy. The main purpose of this investigation was to evaluate the prognostic relevance of the metastatic localisation in unselected patients. The second purpose was to evaluate the impact of clinical characteristics on the kind of decision-making in patients with stage IV NSCLC in an epidemiological manner.[nl]Clinical data as well as survival of 336 patients with stage IV NSCLC were analysed. The recruitment period was 3? years, mean follow-up was 24 months. This investigation was part of the HALLUCA studies which were sponsored by the German Ministry of Health.[nl]Localisation-dependent median and 1-year survivals were significantly different and varied between 2.2 months and 4.7 % (liver metastases) and 11.0 months and 44.5 % (lung metastases). The different survival remained significant in the multivariate analyses with age, performance status, treatment and histology as co variables. The chemotherapy rate of all patients with stage IV NSCLC was 39 %. Patients with liver, bone and multiple metastases received less often chemotherapy compared to patients with other metastases although the performance status was not different to the other groups.[nl]Although there are some limitations in this investigation, these epidemiological data demonstrate the prognostic heterogeneity of stage IV NSCLC patients which should be considered for stratification in controlled clinical trials. Regional treatment decision-making is different from guidelines and controlled clinical trials. Further regionally orientated trials are necessary to improve the transformation from clinical trials to regional medical care. PMID- 20577948 TI - [Current status of erlotinib and gefitinib in palliative therapy for NSCLC--does the EGF-R mutation state have any significance?]. AB - In spite of intensive research and a huge amount of chemotherapy trials, the prognosis of metastastic non-small cell lung cancer (NSCLC) is still poor. Erlotinib and Gefitinb are tyrosine kinase inhibitors (TKIs) which act against the EGF receptor (EGF-R). Activation of mutations in the tyrosine kinase domain leads to an increase in effectiveness. What is the clinical impact of EGF-R mutation screening? What value do TKIs in 1st, 2nd and 3rd line have in therapy for metastatic NSCLC? Which treatment options exist after failure of TKI in the 1st line? These and other clinically relevant questions in the context of TKIs are discussed in the present comprehensive review. PMID- 20577950 TI - Acute scrotum: is scrotal exploration the best management? AB - AIM: Selective scrotal exploration of only those boys believed to have testicular torsion (TT), relying on history and clinical examination for diagnosis, can result in a missed or delayed diagnosis of TT. To minimise testicular loss we propose early scrotal exploration in all boys with acute scrotum (AS). To validate our approach we investigated the accuracy of clinical diagnoses of all boys with AS admitted to our unit. Clinical features and diagnoses were correlated with operative findings. METHODS: A retrospective review of the records of all boys (1-16 years of age) presenting with AS between 2003 and 2007 was done. Overall, 138 boys were seen during this period. Three boys were treated conservatively. The 135 boys who underwent scrotal exploration were divided into three groups: Group A (47 boys) with a history and clinical features considered preoperatively to be consistent with torsion of appendix of testis (TAT); Group B (46 boys) whose characteristics were thought to be more consistent with TT; and finally Group C (42 boys) in whom a preoperative definitive diagnosis could not be made. The preoperative clinical features and diagnoses of the 135 boys were correlated with the operative findings. RESULTS: In Group A, exploration confirmed TAT in 37 (78%) boys, but in 7 (15%) boys it revealed TT. In Group B, exploration confirmed torsion in 31 (68%) boys, but 13 (28%) had TAT. In Group C, exploration revealed 39 (93%) cases of TAT and 3 (7%) cases of TT. CONCLUSION: Surgical exploration in all cases of paediatric AS offers an accurate diagnosis and treatment, thus minimising the risk of testicular loss. PMID- 20577951 TI - Greenstick fractures of the middle third of the forearm. A prospective multi centre study. AB - BACKGROUND: Greenstick fractures suffered during growth have a high risk for refracture and posttraumatic deformity, particularly at the forearm diaphysis. The use of a preemptive completion of the fracture by manipulation of the concave cortex is controversial and data supporting this approach are few. AIM: Aim of this study was to determine the factors which predispose to refracture and deformities, and to define therapeutic strategies. METHODS: We prospectively gathered clinical and radiographic data over a period of one year on greenstick fractures of the middle third of the forearm in children as part of a multi centre study. Endpoint was a follow-up visit at one year. Radiographic deformity, state of consolidation at resumption of physical activities and refracture rate were analysed statistically (ANOVA, Student's t-test and Pearson's chi-square test) with regard to patient age, gender, fracture type, therapy and time in plaster. RESULTS: We collected the data of 103 patients (63 boys, 40 girls), average age 6.6 years (1.3-14.5 years), the vast majority of whom had a combined greenstick fracture of the radius and ulna. 6.7% of the patients sustained a refracture within 49 days (29-76) after plaster removal. They were significantly older (p=0.017) with a significantly higher incidence of manual completion of the fracture with radiographic signs of partial consolidation (p=0.025). Residual deformities were significantly smaller after completion of the fracture compared to reduction without completion (p=0.019) or plaster fixation alone (p<0.005). CONCLUSIONS: Completion of a greenstick fracture does not prevent refracture. Nevertheless, it diminishes the extent of secondary deformities in cases where the primary angulation exceeds the remodelling capacity. Prevention of refracture should include a routine radiographic follow-up 4-6 weeks after injury with continuation of plaster fixation in cases of partial consolidation. PMID- 20577952 TI - Management of prenatally diagnosed abdominal lymphatic malformations. AB - INTRODUCTION: Abdominal lymphatic malformations (ALM) are rare congenital malformations that can regress spontaneously or lead to serious complications. Thus, the appropriate management may be challenging, particularly since pertinent literature is missing. We present our experience in the management of 5 patients with prenatally diagnosed ALM and their outcome and propose a decision-making algorithm. MATERIAL AND METHODS: We retrospectively reviewed the history, diagnostics, therapy, complications, and outcome of 5 patients with a prenatal diagnosis of ALM, referred to our department between January 2006 and February 2008. RESULTS: ALM was prenatally diagnosed by ultrasound in all patients (gestational age 21, 23, 23, 32, and 34 weeks). MRI was performed pre- and postnatally in one patient and postnatally in another. Clinical symptoms ranged from none to respiratory distress and abdominal compartment syndrome. One ALM involuted. 2 patients underwent primary OK-432 treatment. This led to a 70% size reduction in one patient. The other developed massive intracystic bleeding and required emergency surgery. 2/3 patients with surgery needed segmental bowel resection and 3/3 stayed recurrence-free. Complications included one partial inferior vena cava thrombosis after surgery, one subileus, and one hemorrhage after OK-432 application. CONCLUSION: Asymptomatic and regressing ALM are best managed conservatively ("watchful waiting") while symptomatic ALMs require surgery. Further studies are necessary to determine the ideal timepoint for intervention for non-regressing ALM. PMID- 20577953 TI - Surgical management of congenital chylothorax in children. AB - PURPOSE: Aim of the study was to determine the role of surgery in the management of congenital chylothorax (CC). METHODS: We retrospectively reviewed the data of patients with CC requiring medical or surgical treatment postnatally in our institution between January 2001 and March 2009. RESULTS: Ten patients were treated for CC. We divided our population into 2 groups: group A consisted of patients in whom CC healed after conservative medical treatment (thoracocentesis, pleural drainage, total parental nutrition, somatostatin, intrapleural injections of povidone-iodine), and group B of patients who needed both medical and surgical treatment (pleural abrasion and/or pleurectomy). Conservative postnatal therapy was successful in 50% of cases. Of the 3 patients treated preoperatively with intrapleural injections of povidone-iodine, 2 presented with severe complications. Surgical treatment was successful in all cases, with no surgical complications. Patients in group B had a significantly lower birth term (p=0.0254) and birth weight (p=0.0021) compared to patients in group A. Patients with a massive chylothorax (>=50 mL/kg/day) needed surgery significantly more often than those with chylothorax <50 mL/kg/day (p=0.0119). CONCLUSION: The initial postnatal medical management of CC should consist of thoracocentesis, drainage by tube thoracostomy, and total parenteral nutrition. If this treatment fails after 10 days, we propose using alternative therapies such as somatostatin (although its efficacy is not clear) and surgery. Chemical pleurodesis by intrapleural injection of povidone-iodine must be avoided in infants and small babies. Surgical management by pleural abrasion and/or pleurectomy appears to be safe and effective. Early surgical management is proposed for babies with low birth term, birth weight and massive chylothorax >50 mL/kg/day. Long-term follow up is needed to evaluate the potential consequences of this therapy. PMID- 20577954 TI - Cloacal dysgenesis sequence in a set of twins: new insights into embryology and a review of the literature. PMID- 20577955 TI - Bilateral testicular metastasis from Wilms' tumor. PMID- 20577956 TI - Recurrence of immature gastric teratoma with peritoneal gliomatosis. PMID- 20577958 TI - Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios for electronic foetal heart rate monitoring using new evaluation techniques. AB - OBJECTIVE: Hypoxia and acidosis adversely influence many foetal organ functions. We wanted to know how foetal heart rate (FHR) patterns are mirrored by the fetal acid-base status and if they could serve for predicting the actual pH in umbilical artery (UA) blood. For this purpose we condensed the FHR phenomena into one figure which was to be used as a testing variable and to analyse the performance of the new testing procedure. METHODS: The direct FHR signals of 475 foetuses were stored in a computer and analysed offline (MATLAB). All foetuses were delivered by the vaginal route thus without a significant loss of signals. The last 30 min of each recording were used. Acid-base variables and blood gases were determined in cord blood (UA and UV) using RADIOMETER equipments. Three variables of the foetal heart rate (FHR) were computed for each minute: oscillation amplitude [oza (bpm)], microfluctuation [ozm (N/min)] and mean frequency [fhm (bpm)]. These variables were combined to a new index, which we call the WAS index: WAS(T)=FHM(T) x OZF(T)/OZA(T). Using optimisation programmes this index was tailored to actual pH, UA leading to the novel, adapted index: WAS(T)=[FHM(T) x GFHM] x [OZF(T) x GOZF] x [OZA(T) x GOZA]-1,where GFHM, GOZF and GOZA denote three mathematical functions comparable to boundaries in discontinuous scoring-procedures, e. g., the APGAR score. The mean of the WAS index for the last 30 min of delivery is called the WAS score and is used as a discriminator in the testing procedure. WAS score and measured pHUA-values were submitted to correlation and linear regression analysis. Sensitivity, specificity, likelihood ratios, and post-test probabilities were computed including their 95% confidence intervals (CI). A ROC analysis was performed by applying different thresholds for pHUA. RESULTS: pH and WAS score are normally distributed in this sample. The correlation coefficient (r) for pHUA and the WAS score amounts to 0.657, P<<10 (-4). Using ROC plots the area under the curve (AUC) is steadily increased with decreasing pHUA reaching 1.0 for pH 7.0 indicating excellent test accuracy. The AUC for pHUA=7.100 is already 0.963+/ 0.066, 95% CI (0.942-0.978), P<0.001. The positive likelihood ratios (+LR) far exceed 10.0 when lowering the threshold for pHUA. Aiming at a sensitivity of 100% the discriminatory power of the test becomes clinically an optimum when using a discriminator of 1.816 and a threshold pH of 7.122: Sensitivity=100%, specificity=89.3%, FNR=0%, FPR(%)=10.7% and AUC=0.958+/-0.049, 95% CI (0.936 0.974), P<0.001. CONCLUSIONS: Computer-aided evaluation of FHR patterns leads to a novel index (WAS score) which predicts foetal acidaemia with a high level of accuracy. Therefore online WAS scoring is proposed as an ancillary test procedure for future evaluation of FHR patterns. The conventional EFM remains untouched. PMID- 20577959 TI - [Current outcome quality in the care of preterm infants with birth weight less than 1500 grams as a basis for regionalization of risk pregnancies]. PMID- 20577960 TI - [Current outcome quality in the care of preterm infants with birth weight less than 1500 grams as a basis for regionalization of risk pregnancies]. PMID- 20577961 TI - [Molecular tests in modern medicine - concepts, technical aspects and future direction]. AB - Early diagnosis by molecular tests has increasingly catched attention after deciphering the complete human genome sequence in 2001. Meanwhile, complete genome sequencing will soon become available for each individual. Molecular testing is standard of care in certain infectious or malignant diseases. Novel biomarkers are emerging as a result of modern comprehensive procedures (transcriptomics, proteomics, metabolomics etc). However, hype and hope are particularly close in this field and responsible conduct by clinicians will ensure beneficial use of new tests. PMID- 20577962 TI - [Molecular tests for (early) recognition of heart disease - genetic studies in lethal inherited cardiac arrhythmias]. AB - Inherited arrhythmic syndromes can manifest as sudden cardiac death as first, but fatal manifestation. Congenital Long QT Syndrome and Brugada Syndrome affect cardiac repolarisation and are characterised by specific phenotypes on the 12 lead surface ECG. In both syndromes numerous mutations have been identified in the genes encoding the responsible ion channels or other components of the membrane. Two case studies will illustrate aspects of clinical diagnosis including genetic testing and in vitro studies exploring pathophysiology. PMID- 20577963 TI - [Molecular analyses for (early) recognition of hematologic diseases - sense and sensibility for molecular analysis: the art of intelligent decision-making]. AB - During the last 10 years several molecular markers have been established as useful tools among the armamentarium of a hematologist. As a consequence, the number of performed hematologic molecular analyses has immensely increased. Often, such tests replace or complement other laboratory methods. Molecular markers can be useful in many ways: they can serve for diagnostics, describe the prognostic profile, predict which types of drugs are indicated, and can be used for the therapeutic monitoring of the patient to indicate an adequate response or predict resistance or relapse of the disease. Many markers fulfill more than one of these aspects. Most important, however, is the right choice of analyses at the right time-points! PMID- 20577964 TI - [Hereditary breast and ovarian cancer - indications for genetic testing, counseling and options for mutation carriers]. AB - Nowadays, women develop breast and ovarian cancer more and more early. Therefore, gynecologists and primary care physicians encounter the question, whether one of their patients has a genetic predisposition for cancer. They are crucial in initiating a referral for genetic counseling as well as in caring for high risk individuals coming up with questions concerning intensified cancer screening, chemoprevention or prophylactic surgery.This review presents the actual knowledge in these topics and delivers the molecular basis of hereditary breast and ovarian cancer mainly due to mutations in the genes BRCA1 and BRCA2. Problematic aspects of the penetrance of these gene mutations are shown and its role in counseling. The important details of the personal and family history, which influence the risk assessment, are pointed out. Tools for the risk calculation are presented as well as criteria for referral for genetic counseling. The important questions, which have to be addressed in pre- and post-test counseling, are discussed. Finally, the options for women with an inherited predisposition in order to reduce their cancer risk are presented. Each of the three management options 'intensified cancer screening', 'chemoprevention' and 'prophylactic surgery' is discussed thoroughly. Recommended cancer screening in male mutation carriers are mentioned as well. PMID- 20577965 TI - [Molecular tests for (early) recognition of endocrine disorders - towards a sophisticated management of complex endocrine and metabolic diseases]. AB - Genetic testing has a growing impact on clinical medicine in endocrinology. In many disorders, genetic tests permit establishing a diagnosis at the molecular level. Genetic testing has clinical relevance for early carrier detection that may result in early and targeted interventions, and it is important for genetic counseling. Moreover, a detailed understanding of the molecular pathogenesis of endocrine neoplasms is key for the development of novel, more specific therapies. The practitioner should be familiar with key principles and indications for genetic testing. However, it is of importance to recognize potential limitations of genetic analyses, and to inform patients and their relatives accordingly. This review provides a short overview about genetic analyses in the field of endocrinology that are relevant for the practicing physician. PMID- 20577966 TI - [Early genetic testing in nephrology - a diagnostic aid in ambiguous clinical situations]. AB - Despite a growing number of identified genetic causes of monogenetic disorders, early molecular testing is rarely applied in daily nephrologic practice. In selected cases and to answer specific questions, molecular testing however can be helpful for the specialist. The future significance of genetic testing most likely lies in the area of individual risk profiling for polygenetic disorders. The basis for this testing however has yet to be established. PMID- 20577967 TI - [Molecular diagnosis of infectious diseases - a primer for general internists]. AB - The introduction of polymerase chain reaction (PCR)-based DNA amplification in the early nineties has revolutionized diagnosis of infectious diseases and has provided many fundamental insights regarding their epidemiology and clinical presentation. Compared to serology, PCR-based diagnosis may be more specific and sensitive, and may allow earlier diagnosis. Adequate patient specimens are important. Depending on the clinical setting, PCR amplification can be performed on blood samples, other clinical specimens or directly on histopathologic specimens. PCR detection of pathogen DNA is used to confirm serologic screening tests and to diagnose infections due to pathogens that are difficult to grow in culture. With chronically persistent agents, PCR may allow differentiation between clinically irrelevant and relevant infection. Suppression of viral DNA or RNA is a standard read-out of the efficacy of antiviral agents used to treat chronic hepatitis B, C, or HIV infection. Infectious disease consultation may be useful for interpretation of results. Genetic testing is increasingly being performed for antimicrobial susceptibility testing (MRSA, antitubercular treatment) and may in the future contribute to prediction of the host response to infectious disease and of antiretroviral toxicity. Increased future use of PCR based diagnosis of infectious diseases is likely, based on increasingly automated and multiplex PCR technology. PMID- 20577968 TI - Renal macrophage migration and crystal phagocytosis via inflammatory-related gene expression during kidney stone formation and elimination in mice: Detection by association analysis of stone-related gene expression and microstructural observation. AB - Mice have a strong ability to eliminate renal calcium oxalate crystals, and our previous examination indicated a susceptibility in which monocyte-macrophage interaction could participate in the phenomenon. To clarify the macrophage related factors playing roles in the prevention of crystal formation in mouse kidneys, morphologic and expression studies based on microarray pathway analysis were performed. Eight-week-old male C57BL/6N mice were administered 80 mg/kg of glyoxylate by daily intraabdominal injection for 15 days, and the kidneys were extracted every 3 days for DNA microarray analysis. Based on the raw data of microarray analysis, pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokine (C-X-C) ligand 1, fibronectin 1, and major histocompatability (MHC) class II. Association analysis of related gene expression values by quantitative reverse transcription polymerase chain reaction (RT-PCR) indicated the high association of chemokine (C C) ligand 2, CD44, colony-stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1, and transforming growth factor beta1 (TGF beta1) with the amount of both renal crystals and F4/80, a macrophage marker. Immunohistochemically, interstitial macrophages increased during the experimental course, and CD44 and MHC class II were upregulated around crystal-formation sites. Ultrastructural observation of renal macrophages by transmission electron microscopy indicated interstitial macrophage migration with the phagocytosis of crystals. In conclusion, increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte-macrophage migration and phagocytosis via the interaction of CD44 with osteopontin and fibronectin. Such crystal-removing ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation. PMID- 20577969 TI - External referencing and pharmaceutical price negotiation. AB - External referencing (ER) imposes a price cap for pharmaceuticals, based on prices of identical or comparable products in foreign countries. Suppose a foreign country (F) negotiates prices with a pharmaceutical firm, whereas a home country (H) can either negotiate prices independently or implement ER, based on the foreign price. We show that country H prefers ER if copayments in H are relatively high. This preference is reinforced when H's population is small. Irrespective of relative country sizes, ER by country H harms country F. Our model is inspired by the wide European experience with this cost-containment policy. Namely, in Europe, drug authorization and price negotiations are carried out by separate agencies. We confirm our main results in two extensions. The first one allows for therapeutic competition between drugs. In the second one, drug authorization and price negotiation take place in a single agency. PMID- 20577970 TI - NFkappaB: a promising target for natural products in cancer chemoprevention. AB - The transcription factor nuclear factor kappa B (NFkappaB) is found in nearly all animal cell types. It is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL and microbial antigens, and has been shown to regulate the expression of a number of genes including bcl-2, bcl-xl, cIAP, suvivin, TRAF, COX-2, MMP-9, iNOS and cell cycle-regulatory components. Many carcinogens, inflammatory agents and tumor promoters have been shown to activate NFkappaB, and resulting tumors demonstrate misregulated NFkappaB. Incorrect regulation of NFkappaB has been linked to inflammatory and autoimmune diseases, septic shock, viral infection and improper immune development. Aberrant regulation of NFkappaB is involved in cancer development and progression as well as in drug resistance. Inhibitors of NFkappaB mediate effects potentially leading to antitumor responses or greater sensitivity to the action of antitumor agents. Tools have been developed for the rapid assessment of NFkappaB activity, so in concert with a better understanding of NFkappaB activation mechanisms, many agents capable of suppressing NFkappaB activation have been identified. The present article focuses on the functions of NFkappaB, its role in human cancer and the therapeutic potential and benefit of targeting NFkappaB by natural products in cancer chemoprevention. PMID- 20577971 TI - Post-discharge hospital utilization among adult medical inpatients with depressive symptoms. AB - BACKGROUND: Little evidence exists to determine whether depression predicts hospital utilization following discharge among adult inpatients on a general medical service. OBJECTIVE: We aimed to determine whether a positive depression screen during hospitalization is significantly associated with an increased rate of returning for hospital services. DESIGN: A secondary analysis was performed using data from 738 English-speaking, hospitalized adults from the Project RED randomized controlled trial (clinicaltrials.gov Identifier: NCT00252057) conducted at an urban academic safety-net hospital. MEASUREMENTS: We used the nine-item Patient Health Questionnaire (PHQ-9) depression screening tool to identify patients with depressive symptoms. The primary endpoint was hospital utilization, defined as the number of emergency department (ED) visits plus readmissions within 30 days of discharge. Poisson regression was used to control for confounding variables. RESULTS: Of the 738 subjects included in the analysis, 238 (32%) screened positive for depressive symptoms. The unadjusted hospital utilization within 30 days of discharge was 56 utilizations per 100 depressed patients compared with 30 utilizations per 100 non-depressed patients, incident rate ratio (IRR) (confidence interval [CI]), 1.90 (1.51-2.40). After controlling for potential confounders, a higher rate of post-discharge hospital utilization was observed in patients with depressive symptoms compared to patients without depressive symptoms (IRR [CI], 1.73 [1.27-2.36]). CONCLUSIONS: A positive screen for depressive symptoms during an inpatient hospital stay is associated with an increased rate of readmission within 30 days of discharge in an urban, academic, safety-net hospital population. PMID- 20577973 TI - New definitions of extended-spectrum beta-lactamase conferring worldwide emerging antibiotic resistance. AB - Although there is no consensus of the precise definition of ESBL, three kinds of ESBL definitions have been proposed. First, the classical definition includes variants derived from TEM-1, TEM-2, or SHV-1; K1 (KOXY) of Klebsiella oxytoca. Second, the broadened definition has stretched the classical definition of ESBL to include: (1) beta-lactamases (CTX-M-ESBLs, GES-ESBLs, and VEB-ESBLs), with spectra similar to those of TEM and SHV variants (designated as TEM- and SHV ESBLs, respectively) but derived from other sources; (2) TEM and SHV variants with borderline ESBL activity; e.g., TEM-12; and (3) various beta-lactamases conferring wider resistance than their parent types but not meeting the definition for group 2be; e.g., OXA-types (OXA-ESBLs) and mutant AmpC-types (AmpC ESBLs), with increased activity against oxyimino-cephalosporins and with resistance to clavulanic acid. Third, the all-inclusive definition includes: (1) ESBL(A) (named for class A ESBLs); (2) ESBL(M) (miscellaneous ESBLs), which has been subdivided into ESBL(M-C) (class C; plasmid-mediated AmpC) and ESBL(M-D) (class D); and (3) ESBL(CARBA) (ESBLs with hydrolytic activity against carbapenems), which has been subdivided into ESBL(CARBA-A) (class A carbapenemases), ESBL(CARBA-B) (class B carbapenemases), and ESBL(CARBA-D) (class D carbapenemases). The consensus view about the ESBL definition is that the classical ESBL definition must be expanded to class A non-TEM- and non-SHV-ESBLs (CTX-M-, GES-, VEB-ESBLs, etc.). However, these three definitions evoke rational debate on the question "Which would be included in the category of ESBLs among AmpC-ESBLs, OXA-ESBLs, and/or carbapenemases?" Therefore, there is a great need for consensus in the precise definition of ESBL. PMID- 20577972 TI - Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases. AB - Following the discovery of the human kinome, protein kinases have become the second most important group of drug targets as they can be modulated by small ligand molecules. Moreover, orally active protein kinase inhibitors have recently reached the market and there are many more in clinical trials. The lack of treatments for neurodegenerative diseases has increased human and financial efforts in the search for new therapeutic targets that could provide new effective drug candidates. The importance of kinases in the molecular pathway of neuronal survival is under study, but different key pathways have been described. New roles for the old casein kinases 1 and 2, currently known as protein kinases CK1 and CK2, have recently been discovered in the molecular pathology of different neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. The search for specific inhibitors of these enzymes has become an important challenge for the treatment of these devastating diseases. The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review. PMID- 20577974 TI - Potential of carbohydrate-binding agents as therapeutics against enveloped viruses. AB - Twenty-seven years after the discovery of HIV as the cause of AIDS more than 25 drugs directed against four different viral targets (i.e. reverse transcriptase, protease, integrase, envelope gp41) and one cellular target (i.e. CCR5 co receptor) are available for treatment. However, the search for an efficient vaccine is still ongoing. One of the main problems is the presence of a continuously evolving dense carbohydrate shield, consisting of N-linked glycans that surrounds the virion and protects it against efficient recognition and persistent neutralization by the immune system. However, several lectins from the innate immune system specifically bind to these glycans in an attempt to process the virus antigens to provoke an immune response. Across a wide variety of different species in nature lectins can be found that can interact with the glycosylated envelope of HIV-1 and can block the infection of susceptible cells by the virus. In this review, we will give an overview of the lectins from non mammalian origin that are endowed with antiviral properties and discuss the complex interactions between lectins of the innate immune system and HIV-1. Also, attention will be given to different carbohydrate-related modalities that can be exploited for antiviral chemotherapy. PMID- 20577975 TI - Double balloon enteroscopy in Crohn's disease: where are we now and where should we go? AB - Visualization of the entire small-bowel mucosa had not been possible until the development of the capsule endoscope (Pillcam, Given Imaging, Yoqneam, Israel). However, this device did not allow any endoscopic intervention. More recently, a double balloon endoscope has been developed that allows intubation of the entire small bowel. This endoscope contains a working channel that allows for all the interventions possible with standard colonoscopes. In this review we describe the instrument, techniques for its use, and its practical applications and capabilities. We review the experience to date for its use in various clinical indications for small-bowel inflammatory disease, its diagnostic and therapeutic yield and risks, and its role and potential in the diagnosis and treatment of inflammatory bowel disease. PMID- 20577977 TI - Diffusion imaging in humans at 7T using readout-segmented EPI and GRAPPA. AB - Anatomical MRI studies at 7T have demonstrated the ability to provide high quality images of human tissue in vivo. However, diffusion-weighted imaging at 7T is limited by the increased level of artifact associated with standard, single shot, echo-planar imaging, even when parallel imaging techniques such as generalized autocalibrating partially parallel acquisitions (GRAPPA) are used to reduce the effective echo spacing. Readout-segmented echo-planar imaging in conjunction with parallel imaging has the potential to reduce these artifacts by allowing a further reduction in effective echo spacing during the echo-planar imaging readout. This study demonstrates that this approach does indeed provide a substantial improvement in image quality by reducing image blurring and susceptibility-based distortions, as well as by allowing the acquisition of diffusion-weighted images with a high spatial resolution. A preliminary application of the technique to high-resolution diffusion tensor imaging provided a high level of neuroanatomical detail, which should prove valuable in a wide range of applications. PMID- 20577976 TI - Comparison of myocardial perfusion estimates from dynamic contrast-enhanced magnetic resonance imaging with four quantitative analysis methods. AB - Dynamic contrast-enhanced MRI has been used to quantify myocardial perfusion in recent years. Published results have varied widely, possibly depending on the method used to analyze the dynamic perfusion data. Here, four quantitative analysis methods (two-compartment modeling, Fermi function modeling, model independent analysis, and Patlak plot analysis) were implemented and compared for quantifying myocardial perfusion. Dynamic contrast-enhanced MRI data were acquired in 20 human subjects at rest with low-dose (0.019 +/- 0.005 mmol/kg) bolus injections of gadolinium. Fourteen of these subjects were also imaged at adenosine stress (0.021 +/- 0.005 mmol/kg). Aggregate rest perfusion estimates were not significantly different between all four analysis methods. At stress, perfusion estimates were not significantly different between two-compartment modeling, model-independent analysis, and Patlak plot analysis. Stress estimates from the Fermi model were significantly higher (approximately 20%) than the other three methods. Myocardial perfusion reserve values were not significantly different between all four methods. Model-independent analysis resulted in the lowest model curve-fit errors. When more than just the first pass of data was analyzed, perfusion estimates from two-compartment modeling and model-independent analysis did not change significantly, unlike results from Fermi function modeling. PMID- 20577978 TI - Image restoration and spatial resolution in 7-tesla magnetic resonance imaging. AB - A good spatial resolution is essential for high precision segmentations of small structures in magnetic resonance images. However, any increase in the spatial resolution results in a decrease of the signal-to-noise ratio (SNR). In this article, this problem is addressed by a new image restoration technique that is used to partly compensate for the loss in SNR. Specifically, a two-stage hybrid image restoration procedure is proposed where the first stage is a Wiener wavelet filter for an initial denoising. The artifacts that will inevitably be produced by this step are subsequently reduced using a recent variant of anisotropic diffusion. The method is applied to magnetic resonance imaging data acquired on a 7-T magnetic resonance imaging scanner and compared with averaged multiple measurements of the same subject. It was found that the effect of image restoration procedure roughly corresponds to averaging across three repeated measurements. PMID- 20577979 TI - Previous experience of spontaneous or elective abortion and risk for posttraumatic stress and depression during subsequent pregnancy. AB - BACKGROUND: Few studies have considered whether elective and/or spontaneous abortion (EAB/SAB) may be risk factors for mental health sequelae in subsequent pregnancy. This paper examines the impact of EAB/SAB on mental health during subsequent pregnancy in a sample of women involved in a larger prospective study of posttraumatic stress disorder (PTSD) across the childbearing year (n=1,581). METHODS: Women expecting their first baby completed standardized telephone assessments including demographics, trauma history, PTSD, depression, and pregnancy wantedness, and religiosity. RESULTS: Fourteen percent (n=221) experienced a prior elective abortion (EAB), 13.1% (n=206) experienced a prior spontaneous abortion (SAB), and 1.4% (n=22) experienced both. Of those women who experienced either an EAB or SAB, 13.9% (n=220) appraised the EAB or SAB experience as having been "a hard time" (i.e., potentially traumatic) and 32.6% (n=132) rated it as their index trauma (i.e., their worst or second worst lifetime exposure). Among the subset of 405 women with prior EAB or SAB, the rate of PTSD during the subsequent pregnancy was 12.6% (n-51), the rate of depression was 16.8% (n=68), and 5.4% (n-22) met criteria for both disorders. CONCLUSIONS: History of sexual trauma predicted appraising the experience of EAB or SAB as "a hard time." Wanting to be pregnant sooner was predictive of appraising the experience of EAB or SAB as the worst or second worst (index) trauma. EAB or SAB was appraised as less traumatic than sexual or medical trauma exposures and conveyed relatively lower risk for PTSD. The patterns of predictors for depression were similar. PMID- 20577980 TI - Three-dimensional diffusion tensor microimaging for anatomical characterization of the mouse brain. AB - Diffusion tensor imaging is gaining increasing importance for anatomical imaging of the developing mouse brain. However, the application of diffusion tensor imaging to mouse brain imaging at microscopic levels is hindered by the limitation on achievable spatial resolution. In this study, fast diffusion tensor microimaging of the mouse brain, based on a diffusion-weighted gradient and spin echo technique with twin-navigator echo phase correction, is presented. Compared to echo planar and spin echo acquisition, the diffusion-weighted gradient and spin echo acquisition resulted in significant reduction in scan time and had minimal image distortion, thereby allowing acquisition at higher spatial resolution. In this study, three-dimensional diffusion tensor microimaging of the mouse brains at spatial resolutions of 50-60 microm revealed unprecedented anatomical details. Thin fiber bundles in the adult striatum and white matter tracts in the embryonic day 12 mouse brains were visualized for the first time. The study demonstrated that data acquired using the diffusion tensor microimaging technique allow three-dimensional mapping of gene expression data and can serve as a platform to study gene expression patterns in the context of neuroanatomy in the developing mouse brain. PMID- 20577981 TI - Absolute MR thermometry using time-domain analysis of multi-gradient-echo magnitude images. AB - MRI allows for absolute temperature measurements in substances containing two spectral resonances of which the frequency difference Delta f(T) is related to absolute temperature. This frequency difference can be extracted from spectroscopic data. An image-based MR technique that allows for the acquisition of spectroscopic data at high temporal and spatial resolution is the multi gradient-echo sequence. In this work, the application of the multi-gradient-echo sequence for MR thermometry purposes was further developed. We investigated the possibility of postprocessing the multi-gradient-echo data into absolute temperature maps, using time-domain analysis of the magnitude of the multi gradient-echo signals. In this approach, instead of an indirect computation of Delta f(T) from separately found frequencies, Delta f(T) is a direct output parameter. In vitro experiments were performed to provide proof of concept for retrieving absolute temperature maps from the time-domain analysis of multi gradient-echo magnitude images. It is shown that this technique is insensitive to both field drift and local field disturbances. Furthermore, ex vivo bone marrow experiments were performed, using the fat resonance as a reference for absolute temperature mapping. It is shown that the postprocessing based on the magnitude signal in the time domain allows for the determination of Delta f(T) in bone marrow. PMID- 20577982 TI - Four-dimensional spectral-spatial RF pulses for simultaneous correction of B1+ inhomogeneity and susceptibility artifacts in T2*-weighted MRI. AB - Susceptibility artifacts and excitation radiofrequency field B(1)+ inhomogeneity are major limitations in high-field MRI. Parallel transmission methods are promising for reducing artifacts in high-field applications. In particular, three dimensional RF pulses have been shown to be useful for reducing B(1)+ inhomogeneity using multiple transmitters due to their ability to spatially shape the slice profile. Recently, two-dimensional spectral-spatial pulses have been demonstrated to be effective for reducing the signal loss susceptibility artifact by incorporating a frequency-dependent through-plane phase correction. We present the use of four-dimensional spectral-spatial RF pulses for simultaneous B(1)+ and through-plane signal loss susceptibility artifact compensation. The method is demonstrated with simulations and in T(2)*-weighted human brain images at 3 T, using a four-channel parallel transmission system. Parallel transmission was used to reduce the in-plane excitation resolution to improve the slice-selection resolution between two different pulse designs. Both pulses were observed to improve B(1)+ homogeneity and reduce the signal loss artifact in multiple slice locations and several human volunteers. PMID- 20577983 TI - RT-GROG: parallelized self-calibrating GROG for real-time MRI. AB - A real-time implementation of self-calibrating Generalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) operator gridding for radial acquisitions is presented. Self-calibrating GRAPPA operator gridding is a parallel-imaging-based, parameter-free gridding algorithm, where coil sensitivity profiles are used to calculate gridding weights. Self-calibrating GRAPPA operator gridding's weight-set calculation and image reconstruction steps are decoupled into two distinct processes, implemented in C++ and parallelized. This decoupling allows the weights to be updated adaptively in the background while image reconstruction threads use the most recent gridding weights to grid and reconstruct images. All possible combinations of two-dimensional gridding weights G(x)(m)G(y)(n) are evaluated for m,n = {-0.5, -0.4, ..., 0, 0.1, ..., 0.5} and stored in a look-up table. Consequently, the per-sample two-dimensional weights calculation during gridding is eliminated from the reconstruction process and replaced by a simple look-up table access. In practice, up to 34x faster reconstruction than conventional (parallelized) self-calibrating GRAPPA operator gridding is achieved. On a 32-coil dataset of size 128 x 64, reconstruction performance is 14.5 frames per second (fps), while the data acquisition is 6.6 fps. PMID- 20577984 TI - Theory of mind deficits in chronically depressed patients. AB - BACKGROUND: Poor theory of mind (ToM) performance has been found in patients with mood disorders, but it has not been examined in the subgroup of chronic depression where ToM deficits may be even more persistent than in acute depressive episodes. The aim of this study was to compare the ToM performance of chronically depressed patients with a healthy control group and to clarify the relation of ToM to other cognitive functions. METHODS: ToM performance was assessed in 30 chronically depressed patients and 30 matched healthy controls by two cartoon picture story tests. In addition, logical memory, alertness, and executive functioning were evaluated. RESULTS: Chronically depressed patients were markedly impaired in all ToM- and neuropsychological tasks compared to healthy controls. Performance in the different ToM tests was significantly correlated with at least one other cognitive variable. After controlling for logical memory and working memory, no ToM tasks predicted being a patient. CONCLUSIONS: Patients with chronic depression present significant deficits in "reading" social interactions, which may be associated with general cognitive impairments. PMID- 20577985 TI - Reduced electrocortical response to threatening faces in major depressive disorder. AB - BACKGROUND: There is growing support for the emotion context insensitivity hypothesis, which states that major depressive disorder (MDD) is associated with a deficit in emotional reactivity. Under this hypothesis, depressed individuals exhibit reduced behavioral and physiological responses to both appetitive and aversive stimuli. We sought to examine this possibility using the late positive potential, a neural response sensitive to aversive and threatening stimuli. METHODS: Forty-seven individuals participated in the study, 22 of whom met criteria for current MDD and 25 with no history of depression or other Axis I disorders. All individuals passively viewed emotional faces while event-related potentials were recorded. RESULTS: The vertex positive potential was significantly increased in response to fearful and angry faces across the entire sample. The late positive potential was also increased in response to threatening faces, but only among never-depressed individuals. In the MDD group, this electrocortical response to emotional faces was absent. CONCLUSIONS: This study provides neural evidence in support of the view that MDD is associated with blunted emotional reactivity to negative stimuli, which until now has been examined primarily with measures of behavior, self-report, and peripheral physiology. These results are also consistent with two prior studies showing reduced amygdala activation in response to fearful faces among depressed individuals. It remains to be determined whether abnormal activity in response to emotional stimuli is associated with trait risk for MDD or results from MDD. PMID- 20577987 TI - High-performance computing MRI simulations. AB - A new open-source software project is presented, JEMRIS, the Julich Extensible MRI Simulator, which provides an MRI sequence development and simulation environment for the MRI community. The development was driven by the desire to achieve generality of simulated three-dimensional MRI experiments reflecting modern MRI systems hardware. The accompanying computational burden is overcome by means of parallel computing. Many aspects are covered that have not hitherto been simultaneously investigated in general MRI simulations such as parallel transmit and receive, important off-resonance effects, nonlinear gradients, and arbitrary spatiotemporal parameter variations at different levels. The latter can be used to simulate various types of motion, for instance. The JEMRIS user interface is very simple to use, but nevertheless it presents few limitations. MRI sequences with arbitrary waveforms and complex interdependent modules are modeled in a graphical user interface-based environment requiring no further programming. This manuscript describes the concepts, methods, and performance of the software. Examples of novel simulation results in active fields of MRI research are given. PMID- 20577986 TI - Autonomic cardiac control in depressed adolescents. AB - BACKGROUND: The aim of this study was to identify the aspects of cardiac physiology associated with depressive disorder early in life by examining measures of autonomic cardiac control in a community-based sample of depressed adolescents at an early phase of illness, and matched on a number of demographic factors with a nondepressed comparison group. METHODS: Participants were 127 adolescents (44 boys), ages 14-18, who formed two demographically matched groups of clinically depressed and nondepressed participants. Adolescents were excluded if they evidenced comorbid externalizing or substance-dependence disorders, were taking medications with known cardiac effects, or reported regular nicotine use. Resting measures of heart rate, respiratory sinus arrhythmia, skin conductance level, blood pressure, and pre-ejection period were collected. RESULTS: Depressed adolescents had resting heart rates significantly higher than those of healthy adolescents. No other measure of autonomic functioning differentiated the groups. Post hoc analyses were conducted to examine the influence of illness chronicity, severity, comorbidity, and sex on cardiac psychophysiology. These variables did not appear to exert a significant influence on the findings. CONCLUSIONS: Our findings suggest that neither autonomic cardiac control, illness chronicity, or severity, nor medication effects fully explain resting heart rate differences between depressed and nondepressed adolescents. Future research on depression and heart rate should consider mechanisms other than sympathetic or parasympathetic control as potential explanations of heart rate differences, including blood clotting mechanisms, vascular and endothelial dysfunction of the coronary arteries, and inflammatory immune system response. PMID- 20577988 TI - Development and initial validation of the obsessive belief questionnaire-child version (OBQ-CV). AB - BACKGROUND: Cognitive models of obsessive-compulsive disorder (OCD) propose that beliefs are important in the etiology and maintenance of OCD and that these beliefs develop during childhood [Neal et al., 1991: Psychol Bull 109:400-410; Rachman, 1997: Behav Res Ther 35:793-802; Cronbach, 1951: Psychometrika 16:297 334]. However, the ability to test these predictions has been hampered by the lack of a standardized measure of OCD-related beliefs for youth. Therefore, this article presents initial data on a youth version of the widely used Obsessive Belief Questionnaire (OBQ) [Bonett, 2002: J Educ Behav Stat 27:335-340]. METHODS: Data examining the psychometric properties of the Obsessive Belief Questionnaire Child Version (OBQ-CV) are presented from two pediatric OCD samples: a North American (n=29, aged 9-17 years) and a Dutch sample (n=48, aged 8-18 years). RESULTS: Preliminary findings from both samples support the internal consistency, retest reliability, and convergent validity of the OBQ-CV. CONCLUSIONS: Results of this study suggest that the OBQ-CV is a promising tool for examining the role of cognitions in pediatric OCD. Development of the OBQ-CV to augment the existing adult version of the scale creates unique opportunities for investigating the role of cognitions in OCD across the lifespan. PMID- 20577989 TI - Recognition of irrationality of fear and the diagnosis of social anxiety disorder and specific phobia in adults: implications for criteria revision in DSM-5. AB - BACKGROUND: In DSM-IV, the diagnosis of social anxiety disorder (SAD) and specific phobia in adults requires that the person recognize that his or her fear of the phobic situation is excessive or unreasonable (criterion C). The DSM-5 Anxiety Disorders Work Group has proposed replacing this criterion because some patients with clinically significant phobic fears do not recognize the irrationality of their fears. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project we determined the number of individuals who were not diagnosed with SAD and specific phobia because they did not recognize the excessiveness or irrationality of their fear. METHODS: We interviewed 3,000 psychiatric outpatients and 1,800 candidates for bariatric surgery with a modified version of the Structured Clinical Interview for DSM-IV. In the SAD and specific phobia modules we suspended the skip-out that curtails the modules if criterion C is not met. Patients who met all DSM-IV criteria for SAD or specific phobia except criterion C were considered to have "modified" SAD or specific phobia. RESULTS: The lifetime rates of DSM-IV SAD and specific phobia were 30.5 and 11.8% in psychiatric patients and 11.7 and 10.2% in bariatric surgery candidates, respectively. Less than 1% of the patients in both samples were diagnosed with modified SAD or specific phobia. CONCLUSION: Few patients were excluded from a phobia diagnosis because of criterion C. We suggest that in DSM-5 this criterion be eliminated from the SAD and specific phobia criteria sets. PMID- 20577990 TI - Interaction of chronic stress with serotonin transporter and catechol-O methyltransferase polymorphisms in predicting youth depression. AB - BACKGROUND: Investigations of gene-environment interaction (GxE) in depression have implicated a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the stress-depression relationship. However, recent evidence for 5-HTTLPR GxE in depression has been inconsistent. This study examined the moderating effect of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene on the strength of 5-HTTLPR GxE. METHODS: A community sample of youth (n=384) was genotyped for 5-HTTLPR and COMT. A multi-method, multi-informant index of chronic family stress was derived from interviews and questionnaires administered at youth age 15. GxGxE was examined in relation to depression diagnoses between ages 15 and 20 and depressive symptoms at age 20. RESULTS: Significant three-way interactions were observed for both depressive symptoms and diagnoses, such that 5-HTTLPR GxE occurred only in the context of COMT val158 allele homozygosity. For val158 homozygotes, the 5-HTTLPR LL genotype exerted a protective effect in the face of stress. No genetic main effect or two-way GxE was found for 5-HTTLPR. CONCLUSIONS: Inconsistent 5-HTTLPR GxE findings to date may be partly attributable to unmeasured epistatic effects between 5-HTTLPR and COMT val158met. Identifying the conditions under which 5 HTTLPR GxE is most likely to operate may allow depression prevention and treatment efforts to target youth at highest risk. PMID- 20577992 TI - DNA cross-link induced by trans-4-hydroxynonenal. AB - Trans-4-Hydroxynonenal (HNE) is a peroxidation product of omega-6 polyunsaturated fatty acids. Michael addition of HNE to deoxyguanosine yields four diastereomeric 1,N(2)-dG adducts. The adduct of (6S,8R,11S) stereochemistry forms interstrand N(2)-dG:N(2)-dG cross-links in the 5'-CpG-3' sequence. It has been compared with the (6R,8S,11R) adduct, incorporated into 5'-d(GCTAGCXAGTCC)-3' . 5' d(GGACTCGCTAGC)-3', containing the 5'-CpG-3' sequence (X = HNE-dG). Both adducts rearrange in DNA to N(2)-dG aldehydes. These aldehydes exist in equilibrium with diastereomeric cyclic hemiacetals, in which the latter predominate at equilibrium. These cyclic hemiacetals mask the aldehydes, explaining why DNA cross-linking is slow compared to related 1,N(2)-dG adducts formed by acrolein and crotonaldehyde. Both the (6S,8R,11S) and (6R,8S,11R) cyclic hemiacetals are located within the minor groove. However, the (6S,8R,11S) cyclic hemiacetal orients in the 5'-direction, while the (6R,8S,11R) cyclic hemiacetal orients in the 3'-direction. The conformations of the diastereomeric N(2)-dG aldehydes, which are the reactive species involved in DNA cross-link formation, have been calculated using molecular mechanics methods. The (6S,8R,11S) aldehyde orients in the 5'-direction, while the (6R,8S,11R) aldehyde orients in the 3'-direction. This suggests a kinetic basis to explain, in part, why the (6S,8R,11S) HNE adduct forms interchain cross-links in the 5'-CpG-3' sequence, whereas (6R,8S,11R) HNE adduct does not. The presence of these cross-links in vivo is anticipated to interfere with DNA replication and transcription, thereby contributing to the etiology of human disease. PMID- 20577994 TI - Cloning large natural product gene clusters from the environment: piecing environmental DNA gene clusters back together with TAR. AB - A single gram of soil can contain thousands of unique bacterial species, of which only a small fraction is regularly cultured in the laboratory. Although the fermentation of cultured microorganisms has provided access to numerous bioactive secondary metabolites, with these same methods it is not possible to characterize the natural products encoded by the uncultured majority. The heterologous expression of biosynthetic gene clusters cloned from DNA extracted directly from environmental samples (eDNA) has the potential to provide access to the chemical diversity encoded in the genomes of uncultured bacteria. One of the challenges facing this approach has been that many natural product biosynthetic gene clusters are too large to be readily captured on a single fragment of cloned eDNA. The reassembly of large eDNA-derived natural product gene clusters from collections of smaller overlapping clones represents one potential solution to this problem. Unfortunately, traditional methods for the assembly of large DNA sequences from multiple overlapping clones can be technically challenging. Here we present a general experimental framework that permits the recovery of large natural product biosynthetic gene clusters on overlapping soil-derived eDNA cosmid clones and the reassembly of these large gene clusters using transformation-associated recombination (TAR) in Saccharomyces cerevisiae. The development of practical methods for the rapid assembly of biosynthetic gene clusters from collections of overlapping eDNA clones is an important step toward being able to functionally study larger natural product gene clusters from uncultured bacteria. PMID- 20577995 TI - Biosynthesis of lovastatin and related metabolites formed by fungal iterative PKS enzymes. AB - The fungal polyketide lovastatin is a cholesterol lowering agent that is an immediate precursor to a multi-billion dollar drug, simvastatin (Zocor). Lovastatin is produced by an iterative type I polyketide synthase known as LovB and a partner enoyl reductase (LovC). There is evidence that a Diels-Alderase enzyme activity is utilized in its biosynthesis. This review examines the biosynthesis of lovastatin, as well as of compactin, equisetin, cytochalasins, and solanapyrones, which are other structurally related polyketides that appear to utilize a Diels-Alderase. PMID- 20577996 TI - Characterization of a dual specificity aryl acid adenylation enzyme with dual function in nikkomycin biosynthesis. AB - Nikkomycin Z is a dipeptide antifungal antibiotic characterized by two nonproteinogenic amino acids, nikkomycin C(Z) and 4-(4'-hydroxy-2'-pyridinyl) homothreonine (HPHT). The HPHT scaffold is assembled by an aldol reaction between 2-oxobutyrate and picolinaldehyde, the latter of which is derived from picolinic acid that is activated and loaded to coenzyme A by the aryl-activating adenylation enzyme, NikE. We now provide evidence that NikE is also involved in the activation and loading of the alpha-keto acid precursor, 4-(2'-pyridinyl)-2 oxo-4-hydroxyisovalerate (POHIV), to a phosphopantetheinyl group of an acyl carrier protein domain of NikT. POHIV was synthesized using Escherichia coli 2 dehydro-3-deoxy-phosphogluconate aldolase, and phenylalanine dehydrogenase from Bacillus sp. NRRL B-14911 was used to prepare the alpha-amino acid, 4-(2' pyridinyl)-homothreonine (PHT). Using the carboxylic acid-dependent, ATP [(32)P]PP(i) exchange assay, NikE is shown to activate both picolinic acid and POHIV but not PHT. Furthermore, NikE loads POHIV to holo-NikT to generate a new thioester-linked intermediate, which was not observed using a NikT(S33A) mutant. Thus, NikE activates two distinct carboxylic acids to form two new thioester intermediates, one of which is subsequently reduced to the aldehyde and the other that likely serves as a substrate for the aminotransferase domain of NikT prior to condensation with nikkomycin C(Z) to yield the dipeptide. PMID- 20577993 TI - Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignancies. AB - Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. PMID- 20577997 TI - Special series: natural products at the core of drug discovery. PMID- 20577999 TI - DNA interstrand crosslinks: repair, cell signaling, and therapeutic implications. PMID- 20577998 TI - Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites. AB - The tyrosine aminomutase SgTAM produces (S)-ss-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form alpha,ss-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the alpha,ss-unsaturated intermediates to form ss-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis. PMID- 20578000 TI - The serine palmitoyltransferase from Sphingomonas wittichii RW1: An interesting link to an unusual acyl carrier protein. AB - Serine palmitoyltransferase (SPT) catalyses the first step in the de novo biosynthesis of sphingolipids (SLs). It uses a decarboxylative Claisen-like condensation reaction to couple L-serine with palmitoyl-CoA to generate a long chain base product, 3-ketodihydrosphingosine. SLs are produced by mammals, plants, yeast, and some bacteria, and we have exploited the complete genome sequence of Sphingomonas wittichii to begin a complete analysis of bacterial sphingolipid biosynthesis. Here, we describe the enzymatic characterization of the SPT from this organism and present its high-resolution x-ray structure. Moreover, we identified an open reading frame with high sequence homology to acyl carrier proteins (ACPs) that are common to fatty acid biosynthetic pathways. This small protein was co-expressed with the SPT and we isolated and characterised the apo- and holo-forms of the ACP. Our studies suggest a link between fatty acid and sphingolipid metabolism. PMID- 20578002 TI - Recent developments in bisintercalator natural products. AB - The bisintercalator natural products are a family of nonribosomal peptides possessing a range of biological properties that include antiviral, antibiotic, and anticancer activities. The name bisintercalator is derived from the ability to directly bind to duplex DNA through two planar intercalating moieties. Although 19 members of this family of compounds have been identified over the past 50 years, the biosynthetic genes responsible for the formation of four of these molecules (thiocoraline, SW-163, triostin A, and echinomycin) were identified only recently. This recent progress opens an avenue towards understanding how Nature produces these bisintercalating products and provides the potential to develop and identify novel potent analogous lead compounds for clinical applications. This review discusses the mode of action of bisintercalators and summarizes recent genetic and biochemical insights into their biosynthetic production, analog formation, and possible mechanisms by which resistance to these compounds is achieved by their producing organisms. PMID- 20578001 TI - Recent advancements in the biosynthetic mechanisms for polyketide-derived mycotoxins. AB - Polyketides (PKs) are a large group of natural products produced by microorganisms and plants. They are biopolymers of acetate and other short carboxylates and are biosynthesized by multifunctional enzymes called polyketide synthases (PKSs). This review discusses the biosynthesis of four toxic PK, aflatoxins, fumonisins, ochratoxins (OTs), and zearalenone. These metabolites are structurally diverse and differ in their mechanisms of toxicity. However, they are all of concern in food safety and agriculture because of their toxic properties and their frequent accumulation in crops used for food and feed. The focus is on the recent advancements in the understanding of the molecular mechanisms for the biosynthesis of these mycotoxins. Several of the mycotoxin PKSs have been genetically and biochemically studied while other PKSs remain to be investigated. Multiple post-PKS modifications are often required for the maturation of the mycotoxins. Many of these modification steps for aflatoxins and fumonisins are well established while the post-PKS modifications for zearalenone and OTs remain to be biochemically characterized. More efforts are needed to completely illustrate the biosynthetic mechanisms for this important group of PKs. PMID- 20578003 TI - Heterologous expression of the biosynthetic gene clusters of coumermycin A(1), clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains. AB - The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A(1) and of the liponucleoside antibiotic caprazamycin were stably integrated into the genomes of different host strains derived from Streptomyces coelicolor A3(2). For the heterologous expression of clorobiocin derivatives in a chemically defined medium, inclusion of 0.6% of the siloxylated ethylene oxide/propylene oxide copolymer Q2-5247 into the growth medium proved to result in a 4.8-fold increase of productivity. Presumably, this copolymer acts as an oxygen carrier. The additional inclusion of cobalt chloride (0.2-2 mg l(-1)) dramatically increased the percentage of the desired compound clorobiocin within the total produced clorobiocin derivatives. This is very likely due to a stimulation of a cobalamin-dependent methylation reaction catalyzed by the enzyme CloN6 of clorobiocin biosynthesis. All three investigated host strains (S. coelicolor M512, M1146 and M1154) gave similar production rates of total clorobiocin derivatives (on average, 158 mg l(-1) in the presence of 0.6% Q2-5247 and 0.2 mg l(-1) CoCl(2)). In contrast, heterologous production of caprazamycin derivatives was optimal in strain M1154 (amounts of 152 mg l(-1) on average). PMID- 20578004 TI - Risk of malignant neoplasms of liver and biliary tract in diabetic patients with different age and sex stratifications. AB - We prospectively investigated 615,532 diabetic patients and 614,871 age-matched and sex-matched control subjects selected from National Health Insurance claims for malignant neoplasms of liver and biliary tract (International Statistical Classification of Diseases and Related Health Problems, 9th edition, codes 155 and 156, respectively) between 2000 and 2006. The person-year approach with Poisson assumption was used to estimate the hazard rates. We also evaluated the age-specific and sex-specific relative risks of these two malignancies in relation to diabetes with Cox proportional hazard regression model with adjustment for potential confounders. The overall hazard rate of malignant neoplasm of the liver was 32.76 and 17.41 per 10,000 patient-years, respectively, for diabetic men and women; the corresponding figures for biliary tract neoplasm were much lower at 1.42 and 1.60 per 10,000 patient-years. Compared with control subjects, diabetic patients had a two-fold increased risk of malignant neoplasm of the liver, but this risk was attenuated by adjusting for selected clinical risk factors (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.17-1.25). Additionally, diabetic patients were associated with increased risk of biliary neoplasms with an approximate magnitude of 20%-30%, but the HR was attenuated and became insignificant after adjustment for clinical risk factors (HR 1.07; 95% CI 0.95-1.21). Diabetic patients with cirrhosis had the highest relative risk of liver neoplasm (HR 85.25; 95% CI 76.84-94.58), whereas those with cholangitis had the highest risk of biliary tract neoplasm (HR 70.30; 95% CI 51.95-95.12) compared with control subjects without any clinical risk factors. CONCLUSION: This population-based study confirms the association of diabetes with liver neoplasm and suggests that diabetic patients with certain clinical risk factors should be educated for strict adherence of liver neoplasm screening. PMID- 20578006 TI - Intracranial tumor response to respiratory challenges at 3.0 T: impact of different methods to quantify changes in the MR relaxation rate R2*. AB - PURPOSE: To compare two DeltaR2* quantification methods for analyzing the response of intracranial tumors to different breathing gases. The determination of changes in the magnetic resonance imaging (MRI) relaxation rate R2* (DeltaR2*), induced by hyperoxic and hypercapnic respiratory challenges, enables the noninvasive assessment of blood oxygenation changes and vasoreactivity. MATERIALS AND METHODS: Sixteen patients with various intracranial tumors were examined at 3.0 T. The response to respiratory challenges was registered using a dynamic multigradient-echo sequence with high temporal and spatial resolution. At each dynamic step, DeltaR2* was derived in two different ways: 1) by subtraction of R2* values obtained from monoexponential decay functions, 2) by computing DeltaR2* echo-wise from signal intensity ratios. The sensitivity for detection of responding voxels and the behavior of the "global" response were investigated. RESULTS: Significantly more responding voxels (about 4%) were found for method (1). The "global" response was independent from the chosen quantification method but showed slightly larger changes (about 6%) when DeltaR2* was derived from method (1). CONCLUSION: Similar results were observed for the two methods, with a slightly higher detection sensitivity of responding voxels when DeltaR2* was obtained from monoexponential approximation. PMID- 20578007 TI - Quantitative analysis in clinical applications of brain MRI using independent component analysis coupled with support vector machine. AB - PURPOSE: To effectively perform quantification of brain normal tissues and pathologies simultaneously, independent component analysis (ICA) coupled with support vector machine (SVM) is investigated and evaluated for effective volumetric measurements of normal and lesion tissues using multispectral MR images. MATERIALS AND METHODS: Synthetic and real MR data of normal brain and white matter lesion (WML) data were used to evaluate the accuracy and reproducibility of gray matter (GM), white matter (WM), and WML volume measurements by using the proposed ICA+SVM method to analyze three sets of MR images, T1-weighted, T2-weighted, and proton density/fluid-attenuated inversion recovery images. RESULTS: The Tanimoto indexes of GM/WM classification in the normal synthetic data calculated by the ICA+SVM method were 0.82/0.89 for data with 0% noise level. As for clinical MR data experiments, the ICA+SVM method clearly extracted the normal tissues and white matter hyperintensity lesions from the MR images, with low intra- and inter-operator coefficient of variations. CONCLUSION: The experiments conducted provide evidence that the ICA+SVM method has shown promise and potential in applications to classification of normal and pathological tissues in brain MRI. PMID- 20578008 TI - Two-dimensional MR spectroscopy of minimal hepatic encephalopathy and neuropsychological correlates in vivo. AB - PURPOSE: To evaluate regional cerebral metabolic and structural changes in patients with minimal hepatic encephalopathy (MHE) using two-dimensional (2D) MR spectroscopy (MRS) and T( (1) )-weighted MRI, to correlate the observed MR changes with neuropsychological (NP) test scores, and to compare the diagnostic accuracy of MRI, 2D MRS, and NP tests in discriminating between patients and healthy subjects. MATERIALS AND METHODS: Thirty-three MHE patients and 30 healthy controls were investigated. The 2D localized correlated spectroscopy (L-COSY) was performed in the frontal and occipital brain on a 1.5 Tesla (T) MR scanner. The NP test battery included 15 tests, grouped into 6 cognitive domains. Globus pallidus signal intensities were calculated from T(1)-weighted images. RESULTS: The 2D MRS showed significant differences in ratios of the following metabolite(s) peaks with respect to creatine (Cr): decreased myo-inositol (mI), choline (Ch), mICh, and increased (glutamate plus glutamine) (Glx) in patients compared with healthy subjects in both occipital and frontal lobes. Frontal lobe taurine also showed a decline in patients. The NP test results revealed declines in cognitive speed, motor function, executive function, and global cognitive status. Significant correlations were found between the altered metabolites and NP tests. Alteration in the mICh/Cr ratio was noted as a powerful discriminant between healthy subjects and the patients. CONCLUSION: The study demonstrates that relative metabolite levels determined by 2D MRS, in particular mICh/Cr, provide the best diagnostic prediction for MHE. The results suggest that depletions of myo-inositol, choline and taurine with respect to creatine correlate with measures of neuropsychological impairment. PMID- 20578009 TI - MR elastography of the ex vivo bovine globe. AB - PURPOSE: To evaluate the feasibility of using MR elastography (MRE) to assess the mechanical properties of the eye. MATERIALS AND METHODS: The elastic properties of the corneoscleral shell of an intact, enucleated bovine globe specimen were estimated using MRE and finite element modeling (FEM), assuming linear, isotropic behavior. The two-dimensional (2D), axisymetric model geometry was derived from a segmented 2D MR image, and estimations of the Young's modulus in both the cornea and sclera were made at various intraocular pressures using an iterative flexural wave speed matching algorithm. RESULTS: Estimated values of the Young's moduli of the cornea and sclera varied from 40 to 185 kPa and 1 to 7 MPa, respectively, over an intraocular pressure range of 0.85 to 9.05 mmHg (1.2 to 12.3 cmH(2)O). They also varied exponentially as functions of both wave speed and intraocular dP/dV, an empirical measure of "ocular rigidity." CONCLUSION: These results show that it is possible to estimate the intrinsic elastic properties of the corneoscleral shell in an ex vivo bovine globe, suggesting that MRE may provide a useful means to assess the mechanical properties of the eye and its anatomy. Further development of the technique and modeling process will enhance its potential, and further investigations are needed to determine its clinical potential. PMID- 20578010 TI - Visualization of cerebral microbleeds with dual-echo T2*-weighted magnetic resonance imaging at 7.0 T. AB - PURPOSE: To assess the visualization of cerebral microbleeds with dual echo T2* weighted imaging at 7.0 T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ten consecutive participants (eight men, two women, mean age 54 +/- 12 years) with vascular disease or risk factors from the second manifestations of arterial disease (SMART) study were included. Dual-echo T2*-weighted scans (echo time: 2.5/15.0 msec) were made for all participants at 7.0 T MRI. The number of visible microbleeds and the diameter of the microbleeds were recorded on minimal intensity projection images of both echoes. RESULTS: : The first echo image shows dark microbleeds against a homogeneous, more hyperintense signal of the brain tissue without contrast for veins and basal ganglia. In eight patients microbleeds were observed, with a total of 104 microbleeds. Of these, 88 (84.6%) were visible on the first and 102 (98.0%) on the second echo. The mean diameter of the microbleeds was 1.24 mm for the first echo and 2.34 mm for the second echo. CONCLUSION: T2*-weighted imaging at two echo times at 7.0 T combines the advantages of the first and second echo. Microbleeds visible on the first echo show large contrast with the surrounding tissue, even in the presence of paramagnetic ferritin. The second echo enables visualization of smaller microbleeds than the first echo. PMID- 20578011 TI - Reproducibility of in vivo magnetic resonance imaging-based measurement of myelin water. AB - PURPOSE: To evaluate the reproducibility of multicomponent quantitative T(2) (QT2) measurements, in particular the myelin water fraction (MWF), to determine the sensitivity of this method for monitoring myelin changes in longitudinal studies and to provide a basis for correctly powering such studies. MATERIALS AND METHODS: The de facto standard 32-echo spin-echo imaging sequence was used throughout, and data were analyzed using regularized non-negative least squares (NNLS) to produce T(2) distributions. Three studies were conducted in healthy subjects. First, two acquisition protocols were compared in 10 subjects. Second, variability of QT2 was evaluated over same-day scan-rescan experiments in 6 subjects. Finally, variability was quantified in a longitudinal study of 5 subjects. RESULTS: A within-subject coefficient of variation (CoV) of 12% (range 4-25%) was observed for the MWF in brain white matter (WM) regions of interest (ROIs). The geometric mean T(2) was more stable, with a longitudinal CoV of 4% (range 1-6%). The choice of the geometry and repetition time of the acquisition protocol influenced the estimates of the MWF and T(2) values. The choice of integration range for the short-T(2) component had a significant effect on MWF estimates, but not on reproducibility. CONCLUSION: The reproducibility of QT2 measurements using existing methods is moderate and the method can be used in longitudinal studies, with careful consideration of the methodologic variability and an appropriate group size. PMID- 20578012 TI - Microstructural changes in patients with progressive supranuclear palsy: a diffusion tensor imaging study. AB - PURPOSE: To determine whether progressive supranuclear palsy (PSP) is associated with specific diffusion tensor imaging (DTI) patterns of diffusivity, anisotropy, and coherence in functionally relevant brain areas. MATERIALS AND METHODS: In all, 17 PSP patients and 17 controls were scanned using a 3 T magnetic resonance imaging (MRI) scanner. Patients were assessed in the off-medication condition using the Hoehn and Yahr staging and the United Parkinson's Disease Rating Scale, motor subscale (UPDRS-III). Diffusion information were analyzed in relation to disease severity and subtypes. RESULTS: Numerous changes in diffusion properties were identified in the subcortical areas. In the midbrain, fractional anisotropy (FA) decreased and MD (mean diffusivity) increased with disease progression. UPDRS-III scores correlated positively with both FA in the caudate and MD in the pons. DTI analysis of disease subtypes demonstrated significant differences between PSP-Parkinsonism and Steele-Richardson-Olszewski syndrome in axial diffusivity values in the putamen and globus pallidus, as well as in intervoxel diffusion coherence values in the middle cerebellar peduncle. CONCLUSION: Our findings, cautiously interpreted, demonstrate the advantage of using a functional imaging technique to aid in the specificity of defining more precisely the pathological processes taking place in white and gray matter regions in PSP. PMID- 20578013 TI - Diffusion tensor imaging of the pediatric optic nerve: intrinsic and extrinsic pathology compared to normal controls. AB - PURPOSE: To establish normative magnetic resonance diffusion tensor imaging (MRDTI) data in the pediatric optic nerve and compare to pathologic conditions both intrinsic and extrinsic to the anterior optic nerve pathway. MATERIALS AND METHODS: A retrospective analysis of MRDTI at 3.0T in children ages 0-18 with both normal imaging studies and with pathologic conditions either arising from the optic nerves or exerting mass effect on the anterior optic pathways was performed. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained within the posterior part of the intraorbital optic nerves. Statistical analysis compared normal controls to optic pathway lesions. RESULTS: Lesions intrinsic to the optic nerve including septo-optic dysplasia and optic nerve glioma demonstrated statistically significant reductions in FA and increases in ADC values. There was no statistically significant difference in FA or mean diffusivity between the normal controls and patients with lesions extrinsic to the optic nerve but exerting mass effect on the visual pathway. CONCLUSION: MRDTI is a feasible technique for evaluating the optic nerves in pediatric patients. It may play a role in presurgical planning by demonstrating integrity of the visual pathway in patients with resectable lesions, allowing for minimization of morbidity associated with vision loss. PMID- 20578014 TI - Vital signs and cognitive function are not affected by 23-sodium and 17-oxygen magnetic resonance imaging of the human brain at 9.4 T. AB - PURPOSE: To evaluate the effect of 23-sodium ((23)Na) and 17-oxygen ((17)O) magnetic resonance imaging (MRI) at 9.4 (T) on vital signs and cognitive function of the human brain. MATERIALS AND METHODS: Vital sign and cognitive function measurements from healthy volunteers (N = 14) positioned outside and at isocenter of a 9.4 T scanner before and after (23)Na and (17)O MRI were compared for changes due to exposure to the static magnetic field and to the gradient switching and radiofrequency radiation during MRI. RESULTS: Exposure to the 9.4 T static magnetic field and (23)Na and (17)O MRI at 105.92 MHz and 54.25 MHz, respectively, did not have a statistically significant (P > 0.05) effect on the vital signs or cognitive function of healthy normal adults. CONCLUSION: (23)Na and (17)O MRI of the human brain at 9.4 T does not have any readily demonstrated health risks reflected in vital signs or change in cognitive performance. PMID- 20578015 TI - Comparison of dual to single contrast bolus magnetic resonance myocardial perfusion imaging for detection of significant coronary artery disease. AB - PURPOSE: To investigate the incremental diagnostic value of dual-bolus over single-contrast-bolus first pass magnetic resonance myocardial perfusion imaging (MR-MPI) for detection of significant coronary artery disease (CAD). MATERIALS AND METHODS: Patients (n = 49) with suspected CAD underwent first pass adenosine stress and rest MR-MPI and invasive coronary angiography (CA). Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was injected with a prebolus (1 mL) and a large bolus (0.1 mmol/kg). For the single-bolus technique, the arterial input function (AIF) was obtained from the large-contrast bolus. For the dual bolus technique, the AIF was reconstructed from the prebolus. Absolute myocardial perfusion was calculated by Fermi-model constrained deconvolution. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic accuracy of MR myocardial perfusion imaging for detection of significant CAD on CA at vessel-based analysis. RESULTS: The area under the curve (AUC) of the minimal stress perfusion value for the detection of significant CAD using the single-bolus and dual-bolus technique was 0.85 +/- 0.04 (95% confidence interval [CI], 0.77-0.93) and 0.77 +/- 0.05 (95% CI, 0.67-0.86), respectively. CONCLUSION: In this study the dual-bolus technique had no incremental diagnostic value over single-bolus technique for detection of significant CAD with the used contrast concentrations. PMID- 20578016 TI - Morphological features and clinical feasibility of thoracic duct: detection with nonenhanced magnetic resonance imaging at 3.0 T. AB - PURPOSE: To evaluate the detection of the thoracic duct using nonenhanced magnetic resonance imaging (MRI) and to determine the influence of some related disorders on the lymphatic duct. MATERIALS AND METHODS: Highly fluid-sensitive sequence and fat-suppressed T2-weighted imaging (FS-T2WI) were performed in a total of 139 cases. The axial and coronal images were used to locate the thoracic duct and the measurement and evaluation of its dimensions were performed using a 3D maximum intensity projection (MIP) reconstruction image. The differences in the dimensions among control, portal hypertension, and common bile duct obstruction groups were compared using one-way analysis of variance. RESULTS: The cisterna chyli was shown in 91% of cases on FS-T2WI, while the thoracic duct appeared in 70% of the MIP images. The common configuration of the cisterna chyli was tubular or saccular in 73%. Eighty thoracic ducts had a slight turn declining to the left at the level of T8-10. There was a significant difference in the transverse diameter of the thoracic duct between the portal hypertension group and other groups (F = 5.638, P = 0.005). CONCLUSION: Nonenhanced MRI is feasible for locating and depicting the morphological features of the thoracic duct. Portal hypertension may influence the dimension of the thoracic duct. PMID- 20578017 TI - Robust segmentation of mass-lesions in contrast-enhanced dynamic breast MR images. AB - PURPOSE: To develop and evaluate a computerized segmentation method for breast MRI (BMRI) mass-lesions. MATERIALS AND METHODS: A computerized segmentation algorithm was developed to segment mass-like-lesions on breast MRI. The segmentation algorithm involved: (i) interactive lesion selection, (ii) automatic intensity threshold estimation, (iii) connected component analysis, and (iv) a postprocessing procedure for hole-filling and leakage removal. Seven observers manually traced the borders of all slices of 30 mass-lesions using the same tools. To initiate the computerized segmentation, each user selected a seed-point for each lesion interactively using two methods: direct seed-point and robust region of interest (ROI) selections. The manual and computerized segmentations were compared pair-wise using the measured size and overlap to evaluate similarity, and the reproducibility of the computerized segmentation was compared with the interobserver variability of the manual delineations. RESULTS: The observed inter- and intraobserver variations were similar (P > 0.05). Computerized segmentation using the robust ROI selection method was significantly (P < 0.001) more reproducible in measuring lesion size (stDev 1.8%) than either manual contouring (11.7%) or computerized segmentation using directly placed seed point method (13.7%). CONCLUSION: The computerized segmentation method using robust ROI selection is more reproducible than manual delineation in terms of measuring the size of a mass-lesion. PMID- 20578018 TI - Detecting blood oxygen level-dependent (BOLD) contrast in the breast. AB - PURPOSE: To develop a robust technique for detecting blood oxygenation level dependent (BOLD) contrast in the human breast and to evaluate the signal in healthy and malignant breast. MATERIALS AND METHODS: The design of this study focused on determining the optimal pulse sequence and stimulus for detecting BOLD contrast in the breast. For this study a single-shot fast spin echo (SSFSE) sequence was compared to a gradient echo (GRE) pulse sequence. Also, several hyperoxic stimuli were tested on 15 healthy volunteers to determine the best stimulus for inducing BOLD contrast in the breast: air interleaved with carbogen (95% O(2), 5% CO(2)), air interleaved with oxygen, and oxygen interleaved with carbogen. The stimulus with the most consistent results among the healthy population was tested on three breast cancer patients. RESULTS: An SSFSE pulse sequence produced improved BOLD contrast results in the breast compared to a GRE pulse sequence. Oxygen interleaved with carbogen yielded the most consistent results in the healthy population. BOLD contrast in healthy glandular breast tissue positively correlates with carbogen and malignant tissue mostly negatively correlates to carbogen. CONCLUSION: BOLD contrast can consistently be detected in the breast using a robust protocol. This methodology may be used in the future as a noninvasive method for evaluating tumor oxygenation. PMID- 20578019 TI - Value of diffusion-weighted magnetic resonance images for discrimination of focal benign and malignant hepatic lesions: a meta-analysis. AB - PURPOSE: To evaluate the ability of DW-MRI in differentiating malignant hepatic tumors from benign lesions. MATERIALS AND METHODS: Meta-analysis of 14 diagnostic studies was used. A systematic search in Medline, Embase, Web of Science (from January, 1966, to October, 2009), and Cochrane Controlled Clinical Trials Register Database (through third Quarter 2009) was used with screening of the literature. RESULTS: A meta-analysis of all 95 published studies was performed. Fourteen studies fulfilled the inclusion criteria (804 patients with 1665 hepatic lesions). The global sensitivity was 0.91 (95% confidence interval [CI], 0.86 0.94), the specificity was 0.93 (95% CI, 0.86-0.97), the positive likelihood ratio (PLR) was 13.10 (95% CI, 6.30-27.26), the negative likelihood ratio (NLR) was 0.10 (95% CI, 0.06-0.15), and the diagnostic odds ratio (DOR) was 133.76 (95% CI, 49.77-359.45). The area under the curve of the summary receiver operator characteristic (SROC) was 0.96 (95% CI 0.94-0.98). CONCLUSION: Diffusion-weighted magnetic resonance imaging is potential technically feasible to differentiate malignant from benign focal liver lesions. Apparent diffusion coefficient measurements can be useful in providing rapid quantifiable information. PMID- 20578020 TI - Utility of diffusion-weighted MRI in distinguishing benign and malignant hepatic lesions. AB - PURPOSE: To evaluate apparent diffusion coefficient (ADC) values for characterization of a variety of focal liver lesions and specifically for differentiation of solid benign lesions (focal nodular hyperplasia [FNH] and adenomas) from solid malignant neoplasms (metastases and hepatocellular carcinoma [HCC]) in a large case series. MATERIALS AND METHODS: A total of 542 lesions in 382 patients were evaluated. ADC values were measured in 166 hemangiomas, 112 hepatomas, 107 metastases, 95 cysts, 10 abscesses, 43 FNH, and nine adenomas. ADCs of 1.5 and 1.6 (x10(-3) mm(2)/second) were selected as threshold values to separate benign and malignant lesions. Sensitivity, specificity, positive, and negative predictive values (PPV, NPV) were calculated. Comparisons were carried out with studentized range test. RESULTS: There was high interobserver agreement in ADC measurements for all lesion types. The mean ADCs for cysts was 3.40 (x10 ( 3) mm(2)/second), hemangiomas 2.26, FNH 1.79, adenomas 1.49, abscesses 1.97, HCC 1.53, and metastases 1.50. The mean ADC for benign lesions was 2.50 and for malignant lesions was 1.52. Cysts were easily distinguished from other lesions. There was, however, overlap between solid benign and malignant lesions. CONCLUSION: Benign lesions have higher mean ADC values than malignant lesions. However, ADC values of solid benign lesions (FNH and adenomas) are similar to malignant lesions (metastases, HCC) limiting the value of diffusion weighted imaging (DWI) for differentiating solid liver masses. PMID- 20578021 TI - Magnetic resonance histologic correlation in rotator cuff tendons. AB - PURPOSE: To relate histologic changes in rotator cuff tendons to the appearance on T1-weighted as well as fat-suppressed T2-weighted and proton density-weighted magnetic resonance imaging (MRI) sequences. MATERIALS AND METHODS: T1-weighted, fat-suppressed T2-weighted and fat-suppressed proton density-weighted sequences of 18 cadaveric shoulders were acquired. The supraspinatus, infraspinatus, and subscapularis tendons were evaluated histologically. Twenty-six abnormalities were found in 23 of 37 tendons. In addition, histologically normal tendon parts (n = 32), including three segments with normal histology but abnormal MR signal, considered to represent magic angle effects, were defined. All regions of interest (ROIs) were evaluated by two musculoskeletal radiologists independently and blinded to histology. RESULTS: In the 26 areas with anatomically intact tendons but abnormal histological findings mucoid degeneration (n = 13), chondroid metaplasia (n = 11), fatty infiltration (n = 1), and foreign-body granuloma (n = 1) after tendon suture were found. Compared to normal tendon, mucoid degeneration was hyperintense on T2-weighted fat-suppressed (P = 0.007) and on proton density-weighted fat-suppressed images (P = 0.006). Chondroid metaplasia was hyperintense compared to normal tendon in all sequences (P < 0.05). Mucoid degeneration was hypointense compared to chondroid metaplasia on T2 weighted fat-suppressed images (P = 0.038) and hypointense compared to magic angle artifacts on T1-weighted images (P = 0.046). CONCLUSION: Chondroid metaplasia of rotator cuff tendons appears to be more common than expected. Both mucoid degeneration and chondroid metaplasia may explain increased tendon signal on MR images of the rotator cuff. PMID- 20578022 TI - Noninvasive quantification of hepatic steatosis in rats using 3.0 T 1H-magnetic resonance spectroscopy. AB - PURPOSE: To assess the accuracy of noninvasive 3.0 T (1)H-magnetic resonance spectroscopy ((1)H-MRS) in an experimental steatosis model for the discrimination of clinically relevant macrovesicular steatosis degrees and to evaluate three different (1)H-MR spectrum-based fat quantification methods. MATERIALS AND METHODS: Steatosis was induced in rats by a methionine/choline-deficient diet for 0-5 weeks. (1)H-MRS measurements of hepatic fat content were compared with histopathological and biochemical steatosis degree. In (1)H-MR spectra, areas under the curve (AUC) of fat (1.3 ppm), water (4.7 ppm), total fat (0.5-5.3 ppm), and total spectrum peaks (0.5-5.3 ppm) were determined and hepatic fat content calculated as follows: [AUC(total fat peaks)/AUC(total peaks)], [AUC(fat)/AUC(fat) + (AUC(water)/0.7)], and [AUC(fat)/AUC(water)]. RESULTS: A significant correlation was found between (1)H-MRS and macrovesicular steatosis (r = 0.932, P < 0.0001) and between (1)H-MRS and total fatty acids (r = 0.935, P < 0.0001). (1)H-MRS accurately distinguished mild from moderate and moderate from severe steatosis. Calculations using [AUC(fat)/AUC(water)] ratio in severe steatotic livers resulted in higher hepatic fat percentages as compared to the other methods due to a decrease in hepatic water content. CONCLUSION: (1)H-MRS quantification of hepatic fat content showed high correlations with histological and biochemical steatosis determination in an experimental steatosis rat model and accurately discriminated between clinically relevant steatosis degrees. These results encourage further application of (1)H-MRS in patients for accurate steatosis assessment. PMID- 20578023 TI - Reproducibility and correlation between quantitative and semiquantitative dynamic and intrinsic susceptibility-weighted MRI parameters in the benign and malignant human prostate. AB - PURPOSE: To assess the reproducibility of relaxivity- and susceptibility-based dynamic contrast-enhanced magnetic resonance imaging (MRI) in the benign and malignant prostate gland and to correlate the kinetic parameters obtained. MATERIALS AND METHODS: Twenty patients with prostate cancer underwent paired scans before and after androgen deprivation therapy. Quantitative parametric maps for T(1)- and T(2)*-weighted parameters were calculated (K(trans), k(ep),v(e), IAUC(60), rBV, rBF, and R(2)*). The reproducibility of and correlation between each parameter were determined using standard methods at both timepoints. RESULTS: T(1)-derived parameters are more reproducible than T(2)*-weighted measures, both becoming more variable following androgen deprivation (variance coefficients for prostate K(trans) and rBF increased from 13.9%-15.8% and 42.5% 90.8%, respectively). Tumor R(2)* reproducibility improved after androgen ablation (23.3%-11.8%). IAUC(60) correlated strongly with K(trans), v(e), and k(ep) (all P < 0.001). R(2)* did not correlate with other parameters. CONCLUSION: This study is the first to document the variability and repeatability of T(1)- and T(2)*-weighted dynamic MRI and intrinsic susceptibility-weighted MRI for the various regions of the human prostate gland before and after androgen deprivation. These data provide a valuable source of reference for groups that plan to use dynamic contrast-enhanced MRI or intrinsic susceptibility-weighted MRI for the assessment of treatment response in the benign or malignant prostate. PMID- 20578024 TI - Cartilage morphology at 3.0T: assessment of three-dimensional magnetic resonance imaging techniques. AB - PURPOSE: To compare six new three-dimensional (3D) magnetic resonance (MR) methods for evaluating knee cartilage at 3.0T. MATERIALS AND METHODS: We compared: fast-spin-echo cube (FSE-Cube), vastly undersampled isotropic projection reconstruction balanced steady-state free precession (VIPR-bSSFP), iterative decomposition of water and fat with echo asymmetry and least-squares estimation combined with spoiled gradient echo (IDEAL-SPGR) and gradient echo (IDEAL-GRASS), multiecho in steady-state acquisition (MENSA), and coherent oscillatory state acquisition for manipulation of image contrast (COSMIC). Five minute sequences were performed twice on 10 healthy volunteers and once on five osteoarthritis (OA) patients. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured from the volunteers. Images of the five volunteers and the five OA patients were ranked on tissue contrast, articular surface clarity, reformat quality, and lesion conspicuity. FSE-Cube and VIPR-bSSFP were compared to IDEAL-SPGR for cartilage volume measurements. RESULTS: FSE-Cube had top rankings for lesion conspicuity, overall SNR, and CNR (P < 0.02). VIPR-bSSFP had top rankings in tissue contrast and articular surface clarity. VIPR and FSE-Cube tied for best in reformatting ability. FSE-Cube and VIPR-bSSFP compared favorably to IDEAL-SPGR in accuracy and precision of cartilage volume measurements. CONCLUSION: FSE-Cube and VIPR-bSSFP produce high image quality with accurate volume measurement of knee cartilage. PMID- 20578025 TI - In vivo vascular hallmarks of diffuse leukoaraiosis. AB - PURPOSE: To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques. MATERIALS AND METHODS: We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood-brain-barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 +/ 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid-attenuated inversion-recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging. RESULTS: CBF and CVR in leukoaraiosis regions were found to be 39.7 +/- 5.2% (P < 0.001) and 52.5 +/- 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis. CONCLUSION: Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB. PMID- 20578026 TI - Reproducibility of black blood dynamic contrast-enhanced magnetic resonance imaging in aortic plaques of atherosclerotic rabbits. AB - PURPOSE: To investigate the short-term reproducibility of black-blood dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in atherosclerotic rabbits to evaluate the potential of this technique to be a reliable readout of plaque progression and/or regression upon therapeutic intervention. MATERIALS AND METHODS: Atherosclerotic rabbits were imaged at baseline and 24 hours later with DCE-MRI on a 1.5T MRI system. DCE-MRI images were analyzed by calculating the area under the signal intensity versus time curve (AUC). Intraclass correlation coefficients (ICCs) were used to evaluate interscan, intraobserver, and interobserver reproducibility. In addition, the test-retest coefficient of variation (CoV) was evaluated. RESULTS: Statistical analyses showed excellent interscan, intraobserver, and interobserver agreement. All ICCs were greater than 0.75, P < 0.01 indicating excellent agreement between measurements. CONCLUSION: Experimental results show good interscan and excellent intra- and interobserver reproducibility, suggesting that DCE-MRI could be used in preclinical settings as a read-out for novel therapeutic interventions for atherosclerosis. This preliminary work encourages investigating the reproducibility of DCE-MRI also in clinical settings, where it could be used for monitoring high-risk patients and in longitudinal clinical drug trials. PMID- 20578027 TI - Pretreatment and early intratreatment prediction of clinicopathologic response of head and neck cancer to chemoradiotherapy using 1H-MRS. AB - PURPOSE: To determine if choline (cho) identified by proton magnetic resonance spectroscopy ((1)H-MRS) performed pretreatment and early in the course of treatment predicts clinicopathologic response of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In all, 60 patients with HNSCC scheduled to undergo concurrent chemoradiotherapy or radiotherapy alone were recruited. (1)H-MRS was performed pretreatment and early intratreatment (2 weeks after start of treatment). Cho:creatine and cho:water ratios at each timepoint and change in the ratios between the two timepoints were correlated with locoregional failure, distant metastases, overall survival, and cancer-related death. Statistical analysis was performed using logistic regression and chi square and a P-value of < 0.05 was considered statistically significant. RESULTS: Cho was identified in 47/49 successful pretreatment spectra and 42 of these 47 underwent successful (1)H-MRS early intratreatment, of which 21 showed persistent cho. Locoregional failure occurred in 15, distant metastases in 6, and death in 15 patients; the follow-up period in survivors ranged from 13-64 months (mean, 39 months). No statistically significant correlation was found between (1)H-MRS parameters and clinical endpoints. CONCLUSION: The pretreatment cho and change in cho early during a course of treatment did not predict clinical outcome. PMID- 20578028 TI - Iterative image reconstruction for PROPELLER-MRI using the nonuniform fast fourier transform. AB - PURPOSE: To investigate an iterative image reconstruction algorithm using the nonuniform fast Fourier transform (NUFFT) for PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) MRI. MATERIALS AND METHODS: Numerical simulations, as well as experiments on a phantom and a healthy human subject were used to evaluate the performance of the iterative image reconstruction algorithm for PROPELLER, and compare it with that of conventional gridding. The trade-off between spatial resolution, signal to noise ratio, and image artifacts, was investigated for different values of the regularization parameter. The performance of the iterative image reconstruction algorithm in the presence of motion was also evaluated. RESULTS: It was demonstrated that, for a certain range of values of the regularization parameter, iterative reconstruction produced images with significantly increased signal to noise ratio, reduced artifacts, for similar spatial resolution, compared with gridding. Furthermore, the ability to reduce the effects of motion in PROPELLER-MRI was maintained when using the iterative reconstruction approach. CONCLUSION: An iterative image reconstruction technique based on the NUFFT was investigated for PROPELLER MRI. For a certain range of values of the regularization parameter, the new reconstruction technique may provide PROPELLER images with improved image quality compared with conventional gridding. PMID- 20578029 TI - Effect of Gd-EOB-DTPA on T2-weighted and diffusion-weighted images for the diagnosis of hepatocellular carcinoma. AB - PURPOSE: To evaluate the effect of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI) for the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The phantom signal intensity was measured. We also evaluated 72 patients including 30 patients with HCC. T2WI and DWI were obtained before and then 4 and 20 min after injecting the contrast medium. The signal to noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) were calculated in the tumor and liver parenchyma. RESULTS: The phantom signal intensity increased on T2WI at a concentration of contrast medium less than 0.2 mmol/L but decreased when the concentration exceeded 0.4 mmol/L. SNR of the liver parenchyma on T2WI was significantly different between before and 4 min after injecting the contrast medium, while there were no significant differences between before and 4 and 20 min after injection. On T2WI, SNR, and CNR of HCC showed no significant differences at any time. SNR, CNR, and ADC of the liver parenchyma and tumor on DWI also showed no significant differences at any time. CONCLUSION: It is acceptable to perform T2WI and DWI after injection of Gd-EOB-DTPA for the diagnosis of HCC. PMID- 20578030 TI - Comparison of k-t SENSE/k-t BLAST with conventional SENSE applied to BOLD fMRI. AB - PURPOSE: To compare k-t BLAST (broad-use linear-acquisition speedup technique)/k t SENSE (sensitivity encoding) with conventional SENSE applied to a simple fMRI paradigm. MATERIALS AND METHODS: Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed at 3 T using a displaced ultra fast low-angle refocused echo (UFLARE) pulse sequence with a visual stimulus in a block paradigm. Conventional SENSE and k-t BLAST/k-t SENSE data were acquired. Also, k-t BLAST/k-t SENSE was simulated at different undersampling factors from fully sampled data after removal of lines of k-space data. Analysis was performed using SPM5. RESULTS: Sensitivity to the BOLD response in k-t BLAST/k-t SENSE was comparable with that of SENSE in images acquired at an undersampling factor of 2.3. Simulated k-t BLAST/k-t SENSE yielded reliable detection of activation induced BOLD contrast at undersampling factors of 5 or less. Sensitivity increased significantly when training data were included in k-space before Fourier transformation (known as "plug-in"). CONCLUSION: k-t BLAST/k-t SENSE performs at least as well as conventional SENSE for BOLD fMRI at a modest undersampling factor. Results suggest that sufficient sensitivity to BOLD contrast may be achievable at higher undersampling factors with k-t BLAST/k-t SENSE than with conventional parallel imaging approaches, offering particular advantages at the highest magnetic field strengths. PMID- 20578031 TI - Reduced field-of-view single-shot fast spin echo imaging using two-dimensional spatially selective radiofrequency pulses. AB - PURPOSE: To demonstrate reduced field-of-view (RFOV) single-shot fast spin echo (SS-FSE) imaging based on the use of two-dimensional spatially selective radiofrequency (2DRF) pulses. MATERIALS AND METHODS: The 2DRF pulses were incorporated into an SS-FSE sequence for RFOV imaging in both phantoms and the human brain on a 1.5 Tesla (T) whole-body MR system with the aim of demonstrating improvements in terms of shorter scan time, reduced blurring, and higher spatial resolution compared with full FOV imaging. RESULTS: For phantom studies, scan time gains of up to 4.2-fold were achieved as compared to the full FOV imaging. For human studies, the spatial resolution was increased by a factor of 2.5 (from 1.7 mm/pixel to 0.69 mm/pixel) for RFOV imaging within a scan time (0.7 s) similar to full FOV imaging. A 2.2-fold shorter scan time along with a significant reduction of blurring was demonstrated in RFOV images compared with full FOV images for a target spatial resolution of 0.69 mm/pixel. CONCLUSION: RFOV SS-FSE imaging using a 2DRF pulse shows advantages in scan time, blurring, and specific absorption rate reduction along with true spatial resolution increase compared with full FOV imaging. This approach is promising to benefit fast imaging applications such as image guided therapy. PMID- 20578032 TI - In vivo observation of the locomotion of microglial cells in the retina. AB - Microglial cells (MCs) are active sensors and reactive phagocytes of neural tissues. They are known to migrate and accumulate in areas of neuronal damage. Thus, microglial locomotion is an essential feature of the inflammatory reaction in neural tissue. Yet, to our knowledge there has been no report of direct in vivo observation of the migration of MCs. Here, we show that intravitreally injected cyanine dyes (DiO, DiI, and indocyanine green) are sequestrated in MCs during several months, and subsequently in vivo images of these fluorescent MCs can be obtained by confocal scanning laser ophthalmoscopy. This enabled noninvasive, time-lapse observation of the migrating behavior of MCs, both in the basal state and following laser damage. In the basal state, a slow, intermittent, random-like locomotion was observed. Following focal laser damage, MCs promptly (i.e., within 1 h) initiated centripetal, convergent migration. MCs up to 400 MUm away migrated into the scar at velocities up to 7 MUm/min. This early phase of centripetal migration was followed by a more prolonged phase of nontargeted locomotion around and within injured sites during at least 24 h. Cyanine-positive cells persisted within the scar during several weeks. To our knowledge, this is the first in vivo observation of the locomotion of individual MCs. Our results show that the locomotion of MCs is not limited to translocation to acutely damaged area, but may also be observed in the basal state and after completion of the recruitment of MCs into scars. PMID- 20578033 TI - Electroencephalography (EEG) and event-related potentials (ERPs) with human participants. AB - Understanding the basic neural processes that underlie complex higher-order cognitive operations and functional domains is a fundamental goal of cognitive neuroscience. Electroencephalography (EEG) is a non-invasive and relatively inexpensive method for assessing neurophysiological function that can be used to achieve this goal. EEG measures the electrical activity of large, synchronously firing populations of neurons in the brain with electrodes placed on the scalp. This unit outlines the basics of setting up an EEG experiment with human participants, including equipment, and a step-by-step guide to applying and preparing an electrode cap. Also included are support protocols for two event related potential (ERP) paradigms, P50 suppression, and mismatch negativity (MMN), which are measures of early sensory processing. These paradigms can be used to assess the integrity of early sensory processing in normal individuals and clinical populations, such as individuals with schizophrenia. PMID- 20578034 TI - Isolation of mitochondria from the CNS. AB - This unit contains a protocol describing the isolation of brain mitochondria by using discontinuous Percoll gradient centrifugation. The Percoll density gradient centrifugation separates synaptosomes, myelin, and free nonsynaptic mitochondria released from cells during tissue homogenization into individual fractions. Mitochondria entrapped in synaptosomes (synaptic mitochondria) can be liberated using nitrogen cavitation and then further purified by Percoll gradient centrifugation. These methods yield mitochondria that exhibit good respiratory coupling and high respiratory rates. PMID- 20578035 TI - Analyzing binding data. AB - Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments. PMID- 20578036 TI - A murine model of atypical antipsychotic-induced weight gain and metabolic dysregulation. AB - In comparison with conventional, first-generation antipsychotics (e.g., haloperidol), the administration of atypical antipsychotics (AAPs) has been associated with a higher risk of metabolic derangements, including body weight increase, dysregulation of glucose homeostasis, fat accumulation, and even liability to develop type II diabetes. Since this is a serious clinical problem that may be further exacerbated in overweight schizophrenics, establishing animal models of AAP-induced adverse effects may contribute to clarifying the mechanisms underlying these effects. Here we present three basic protocols by which this problem has been modeled. The three protocols differ in many aspects (routes of administration, extent of the chronic treatment, diets, and dosage regimen), and the pros and cons of each procedure are systematically detailed throughout. It should be noted that several factors (e.g., species, sex, duration, and class of AAPs) could restrict the feasibility of these models, as well as their correspondence to the clinical condition. PMID- 20578037 TI - A homologous form of human interleukin 16 is implicated in microglia recruitment following nervous system injury in leech Hirudo medicinalis. AB - In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin 16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair. PMID- 20578038 TI - Morphine induces the release of CCL5 from astrocytes: potential neuroprotective mechanism against the HIV protein gp120. AB - A number of human immunodeficiency virus type-1 (HIV) positive subjects are also opiate abusers. These individuals are at high risk to develop neurological complications. However, little is still known about the molecular mechanism(s) linking opiates and HIV neurotoxicity. To learn more, we exposed rat neuronal/glial cultures prepared from different brain areas to opiate agonists and HIV envelope glycoproteins gp120IIIB or BaL. These strains bind to CXCR4 and CCR5 chemokine receptors, respectively, and promote neuronal death. Morphine did not synergize the toxic effect of gp120IIIB but inhibited the cytotoxic property of gp120BaL. This effect was blocked by naloxone and reproduced by the mu opioid receptor agonist DAMGO. To examine the potential mechanism(s) of neuroprotection, we determined the effect of morphine on the release of chemokines CCL5 and CXCL12 in neurons, astrocytes, and microglia cultures. CCL5 has been shown to prevent gp120BaL neurotoxicity while CXCL12 decreases neuronal survival. Morphine elicited a time-dependent release of CCL5 but failed to affect the release of CXCL12. This effect was observed only in primary cultures of astrocytes. To examine the role of endogenous CCL5 in the neuroprotective activity of morphine, mixed cerebellar neurons/glial cells were immunoneutralized against CCL5 prior to morphine and gp120 treatment. In these cells the neuroprotective effect of opiate agonists was blocked. Our data suggest that morphine may exhibit a neuroprotective activity against M-tropic gp120 through the release of CCL5 from astrocytes. PMID- 20578039 TI - Dynamic expression of Cx47 in mouse brain development and in the cuprizone model of myelin plasticity. AB - The study shows the dynamic expression of connexin47 (Cx47) in oligodendrocytes and myelin of mice, either in myelinogenesis occurring in early development or in an experimental model of new-myelinogenesis of adult mice. Cx47 first appeared in the embryonic mouse brain at E10.5 successively the expression increased, principally in regions populated by developing oligodendrocytes. The expression declined postnatally toward adulthood and immunoreactivity was restricted to a few specific areas, such as the corpus callosum, the striatum, the cerebellum, and the spinal cord. Since the expression of Cx47 in developing oligodendrocytes preceded those of Cx32 and Cx29, a role of Cx47 in myelinogenesis was postulated. This hypothesis was tested in a model of re-myelination, which principally involved the corpus callosum, occurring in adult mice by treatment with cuprizone. Cx47 was upregulated during demyelination and recovered during the remyelination phase. During demyelination, Cx47 was first over-expressed in the corpus callosum and later, when the myelin virtually disappeared in the injured areas, Cx47 was expressed in astrocytes located inside and closely around the demyelinated areas. The remyelination of injured areas occurred after stopping the administration of cuprizone and continued to complete recovery. In this period the expression of Cx47 shifted from astrocytes to newly-formed myelin. Thus, Cx47 exhibits in this model a transient and de novo expression in astrocytes with a topographic segregation in the injured areas, only when oligodendrocytes and the myelin were most severely affected. Taken as a whole the evidence suggests that Cx47 play a key role in myelination. PMID- 20578040 TI - Organization of glial cells in the adult sea cucumber central nervous system. AB - The nervous system of echinoderms has long been considered too unique to be directly comparable to the nervous system of other Deuterostomia. Using two novel monoclonal antibodies in combination with epifluorescence, confocal, and electron microscopy, we demonstrate here that the central nervous system of the sea cucumber Holothuria glaberrima possesses a major non-neuronal cell type, which shares striking similarities with the radial glia of chordates. The basic features in common include (a) an elongated shape, (b) long radial processes, (c) short lateral protrusions branching off the main processes and penetrating into the surrounding neuropile, (d) prominent orderly oriented bundles of intermediate filaments, and (e) ability to produce Reissner's substance. Radial glia account for the majority of glia cells in echinoderms and constitutes more than half of the total cell population in the radial nerve cord and about 45% in the circumoral nerve ring. The difference in glia cell number between those regions is significant, suggesting structural specialization within the seemingly simple echinoderm nervous system. Both cell death and proliferation are seen under normal physiological conditions. Although both glia and neurons undergo apoptosis, most of the mitotic cells are identified as radial glia, indicating a key role of this cell type in cell turnover in the nervous system. A hypothesis is proposed that the radial glia could be an ancestral feature of the deuterostome nervous system, and the origin of this cell type might have predated the diversification of the Chordata and Ambulacraria lineages. PMID- 20578041 TI - Toll-like receptor expression in the peripheral nerve. AB - Toll-like receptors comprise a family of evolutionary conserved pattern recognition receptors that act as a first defense line in the innate immune system. Upon stimulation with microbial ligands, they orchestrate the induction of a host defense response by activating different signaling cascades. Interestingly, they appear to detect the presence of endogenous signals of danger as well and as such, neurodegeneration is thought to trigger an immune response through ligation of TLRs. Though recent data report the expression of various TLRs in the central nervous system, TLR expression patterns in the peripheral nervous system have not been determined yet. We observed that Schwann cells express relatively high levels of TLRs, with especially TLR3 and TLR4 being prominent. Sensory and motor neurons hardly express TLRs at all. Through the use of NF-kappaB signaling as read-out, we could show that all TLRs are functional in Schwann cells and that bacterial lipoprotein, a ligand for TLR1/TLR2 receptors yields the strongest response. In sciatic nerve, basal levels of TLRs closely reflect the expression patterns as determined in Schwann cells. TLR3, TLR4, and TLR7 are majorly expressed, pointing to their possible role in immune surveillance. Upon axotomy, TLR1 becomes strongly induced, while most other TLR expression levels remain unaffected. Altogether, our data suggest that similar to microglia in the brain, Schwann cells might act as sentinel cells in the PNS. Furthermore, acute neurodegeneration induces a shift in TLR expression pattern, most likely illustrating specialized functions of TLRs in basal versus activated conditions of the peripheral nerve. PMID- 20578042 TI - Involvement of p300 in constitutive and HIV-1 Tat-activated expression of glial fibrillary acidic protein in astrocytes. AB - HIV-1 Tat protein is an important pathogenic factor in HIV-1-associated neurological diseases. One hallmark of HIV-1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated glial fibrillary acidic protein (GFAP) expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes [Zhou et al., (2004) Mol Cell Neurosci 27:296-305] and that GFAP is an important regulator of Tat neurotoxicity [Zou et al., (2007) Am J Pathol 171:1293-1935]. However, the underlying mechanisms for Tat-mediated GFAP up-regulation are not understood. In this study, we reported concurrent up regulation of adenovirus E1a-associated 300 kDa protein p300 and GFAP in Tat expressing human astrocytoma cells and primary astrocytes. We showed that p300 was indeed induced by Tat expression and HIV-1 infection and that the induction occurred at the transcriptional level through the cis-acting elements of early growth response 1 (egr-1) within its promoter. Using siRNA, we further showed that p300 regulated both constitutive and Tat-mediated GFAP expression. Moreover, we showed that ectopic expression of p300 potentiated Tat transactivation activity and increased proliferation of HIV-1-infected astrocytes, but had little effect on HIV-1 replication in these cells. Taken together, these results demonstrate for the first time that Tat is a positive regulator of p300 expression, which in turn regulates GFAP expression, and suggest that the Tat-Egr 1-p300-GFAP axis likely contributes to Tat neurotoxicity and predisposes astrocytes to be an HIV-1 sanctuary in the CNS. PMID- 20578044 TI - Reduction of errors in ASL cerebral perfusion and arterial transit time maps using image de-noising. AB - In this work, the performance of image de-noising techniques for reducing errors in arterial spin labeling cerebral blood flow and arterial transit time estimates is investigated. Simulations were used to show that the established arterial spin labeling cerebral blood flow quantification method exhibits the bias behavior common to nonlinear model estimates, and as a result, the reduction of random errors using image de-noising can improve accuracy. To assess the effect on precision, multiple arterial spin labeling data sets acquired from the rat brain were processed using a variety of common de-noising methods (Wiener filter, anisotropic diffusion filter, gaussian filter, wavelet decomposition, and independent component analyses). The various de-noising schemes were also applied to human arterial spin labeling data to assess the possible extent of structure degradation due to excessive spatial smoothing. The animal experiments and simulated data show that noise reduction methods can suppress both random and systematic errors, improving both the precision and accuracy of cerebral blood flow measurements and the precision of transit time maps. A number of these methods (and particularly independent component analysis) were shown to achieve this aim without compromising image contrast. PMID- 20578043 TI - Activation of PPAR-gamma and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cells. AB - Previously, we and others documented that statins including-lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a cuprizone-CNS demyelinating model. Therefore, herein, we first investigated the cause of impaired differentiation of OLs by statins in vitro settings. Our observations indicated that the depletion of cholesterol was detrimental to LOV treated OPCs under cholesterol/serum-deprived culture conditions similar to that were used in conflicting studies. However, the depletion of geranylgeranyl-pp under normal cholesterol homeostasis conditions enhanced the phenotypic commitment and differentiation of LOV-treated OPCs ascribed to inhibition of RhoA-Rho kinase. Interestingly, this effect of LOV was associated with increased activation and expression of both PPAR-gamma and PTEN in OPCs as confirmed by various pharmacological and molecular based approaches. Furthermore, PTEN was involved in an inhibition of OPCs proliferation via PI3K Akt inhibition and induction of cell cycle arrest at G1 phase, but without affecting their cell survival. These effects of LOV on OPCs in vitro were absent in the CNS of normal rats chronically treated with LOV concentrations used in EAE indicating that PPAR-gamma induction in normal brain may be tightly regulated providing evidences that statins are therapeutically safe for humans. Collectively, these data provide initial evidence that statin-mediated activation of the PPAR-gamma-PTEN cascade participates in OL differentiation, thus suggesting new therapeutic-interventions for MS or related CNS-demyelinating diseases. PMID- 20578045 TI - Problems after discharge and understanding of communication with their primary care physicians among hospitalized seniors: a mixed methods study. AB - BACKGROUND: Communication and coordination with primary care physicians (PCPs) is recommended to ensure safe care transitions for hospitalized older patients. Understanding patient experiences of problems after discharge can help clinical teams design more patient-centered care transitions. OBJECTIVE: To report older patients' experiences with problems after hospital discharge and investigate whether PCPs were aware of their hospitalization. DESIGN: Prospective mixed methods study. SETTING: Single academic medical center. PATIENTS: Hospitalized patients and PCPs. MEASUREMENTS: Telephone interviews of frail, older general medical patients conducted 2 weeks after discharge to elicit patient problems after discharge, such as: (1) obtaining medications, or follow-up appointments; and (2) perceptions of hospital physician communication with their PCP. For each patient interviewed, their PCP was faxed a survey 2 weeks after discharge to assess awareness of hospitalization. RESULTS: Forty-two percent (27) of patients reported 42 different post-discharge problems. The most frequently reported problems were difficulty with follow-up appointments or tests (12). Other reported problems included readmission and return to the Emergency Department (10), problems with medications (8), not-prepared for discharge (8), and hospital complications or questions (4). Thirty percent of PCPs were unaware of patient hospitalization. Patients were twice as likely to report a problem if their PCP was unaware of the hospitalization (31% PCP aware, vs. 67% PCP not aware; P < 0.05). CONCLUSION: This study suggests that many frail, older patients reported problems after discharge and were twice as likely to do so when the patient's PCP was not aware of the hospitalization. Systematic interventions to improve communication with PCPs during patient hospitalization are needed. PMID- 20578046 TI - Post-hospitalization transitions: Examining the effects of timing of primary care provider follow-up. AB - BACKGROUND: The transition between the inpatient and outpatient setting is a high risk period for patients. The presence and role of the primary care provider (PCP) is critical during this transition. This study evaluated characteristics and outcomes of discharged patients lacking timely PCP follow-up, defined as within 4 weeks of discharge. METHODS: This prospective cohort enrolled 65 patients admitted to University of Colorado Hospital, an urban 425-bed tertiary care center. We collected patient demographics, diagnosis, payer source and PCP information. Post-discharge phone calls determined PCP follow-up and readmission status. Thirty-day readmission rate and hospital length of stay (LOS) were compared in patients with and without timely PCP follow-up. RESULTS: The rate of timely PCP follow-up was 49%. For a patient's same medical condition, the 30-day readmission rate was 12%. Patients lacking timely PCP follow-up were 10 times more likely to be readmitted (odds ratio [OR] = 9.9, P = 0.04): 21% in patients lacking timely PCP follow-up vs. 3% in patients with timely PCP follow-up, P = 0.03. Lack of insurance was associated with lower rates of timely PCP follow-up: 29% vs. 56% (P = 0.06), but did not independently increase readmission rate or LOS (OR = 1.0, P = 0.96). Index hospital LOS was longer in patients lacking timely PCP follow-up: 4.4 days vs. 6.3 days, P = 0.11. CONCLUSIONS: Many patients discharged from this large urban academic hospital lacked timely outpatient PCP follow-up resulting in higher rates of readmission and a non-significant trend toward longer hospital LOS. Effective transitioning of care for vulnerable patients may require timely PCP follow-up. PMID- 20578047 TI - Performance of Dutch hospitals in the management of splenectomized patients. AB - BACKGROUND: After splenectomy, patients are at increased risk of sepsis with considerable mortality. This risk can be reduced by taking preventive measures, such as prescribing immunizations and antibiotic prophylaxis. Studies from various countries show that a substantial percentage of patients are not managed adequately. The aim of the present study was to investigate the quality of care in the prevention of infections after splenectomy in Dutch hospitals. The research questions were two-fold: (1) Is there an association between hospital teaching status and guideline adherent preventive measures? (2) Which factors contribute to hospital performance? METHODS: A total of 28 Dutch hospitals (30%) participated in the study. A retrospective review of medical records of 536 splenectomy patients was performed. Adherence to prevention guidelines was assessed for all patients, and analyzed according to teaching status and the presence or absence of a post-splenectomy protocol. RESULTS: (1) University hospitals in the Netherlands offered higher quality of care than other teaching and nonteaching hospitals. There were only small differences between nonuniversity teaching and nonteaching hospitals. (2) The presence of a hospital post-splenectomy protocol did not improve vaccination rates. Other aspects of practice organization, such as surgical staff size and keeping a complication registry were only weakly related to performance. CONCLUSIONS: In the Netherlands, university hospitals deliver state-of-the-art care in the prevention of infections in asplenic patients more often than nonuniversity teaching and nonteaching hospitals. The availability of a hospital protocol does not seem to contribute to guideline adherence. PMID- 20578048 TI - Necrotizing fasciitis associated with acupuncture: a case report. AB - Infectious complications from acupuncture are extremely rare; we present a case of severe necrotizing Fasciitis (type 1) in an elderly nondiabetic male. PMID- 20578049 TI - Trends in thrombolytic use for ischemic stroke in the United States. AB - BACKGROUND: Although recombinant tissue plasminogen activator (tPA) improves outcomes from ischemic stroke, prior studies have found low rates of administration. Recent guidelines and regulatory agencies have advocated for increased tPA administration in appropriate patients, but it is unclear how many patients actually receive tPA. OBJECTIVE: To determine whether national rates of tPA use for ischemic stroke have increased over time. METHODS: We identified all patients with a primary diagnosis of ischemic stroke from years 2001 to 2006 in the National Hospital Discharge Survey (NHDS), a nationally representative sample of inpatient hospitalizations, and searched for procedure codes for intravenous thrombolytic administration. Clinical and demographic factors were obtained from the survey and multivariable logistic regression used to identify independent predictors associated with thrombolytic use. RESULTS: Among the 22,842 patients hospitalized with ischemic stroke, tPA administration rates increased from 0.87% in 2001 to 2.40% in 2006 (P < 0.001 for trend). Older patients were less likely to receive tPA (adjusted odds ratio [OR] and 95% confidence interval [CI]; 0.4 [0.3-0.6] for patients >=80 years vs. <60 years), as were African American patients (0.4 [0.3-0.7]). Larger hospitals were more likely to administer tPA (3.3 [2.0-5.6] in hospitals with at least 300 beds compared to those with 6-99 beds). CONCLUSIONS: Although tPA administration for ischemic stroke has increased nationally in recent years, the overall rate of use remains very low. Larger hospitals were more likely to administer tPA. Further efforts to improve appropriate administration of tPA should be encouraged, particularly as the acceptable time-window for using tPA widens. PMID- 20578050 TI - Short-term femoral vein catheterization rarely causes thrombosis or bacteremia. AB - BACKGROUND: Experts and national regulatory bodies have deemed femoral vein catheterization (FVC) unsafe, and recommend avoiding it whenever possible. OBJECTIVE: To assess rates of catheter-related bloodstream infections (CRBI) and deep venous thrombosis (DVT) complicating FVC. DESIGN: Prospective observational cohort study. SETTING: Medical intensive care unit (MICU) of a 350-bed community teaching hospital. PATIENTS: Consecutive admissions to the MICU during 7 months. METHODS: Demographic, laboratory and Doppler ultrasound studies were collected on patients receiving large vein catheters (VC) in our MICU. Ultrasound examinations were systematically performed on the day of and 5 to 7 days after removal of FVC. RESULTS: VC were inserted in 238 (35% of) patients. Of that total, 217 catheters were in large veins (49% FVC, 38% internal jugular and 13% subclavian) for an average of 2.7 days for femoral, 5.7 days for internal jugular and 3.6 days for subclavian vein catheters. During 1200 catheter-days, no central VC CRBI was identified. Of 107 FVC, initial and follow-up Doppler studies were performed in 50 patients. A total of 97% of patients received routine thromboprophylaxis and none had a DVT. Of the 57 patients with initial but no Doppler follow-up at 5 to 7 days following removal, no patient developed clinically detected venous thromboembolism (VTE). CONCLUSION: Short-term FVC was used safely in our MICU in the setting of thromboprophylaxis. In light of its favorable safety profile for initial resuscitation of critically ill patients, it may be premature to strongly discourage FVC. PMID- 20578051 TI - Calciphylaxis (calcific uremic arteriolopathy) in a patient with chronic kidney disease. PMID- 20578052 TI - Magnetic resonance elastography as a method for the assessment of effective myocardial stiffness throughout the cardiac cycle. AB - MR elastography (MRE) is a noninvasive technique in which images of externally generated waves propagating in tissue are used to measure stiffness. The first aim is to determine, from a range of driver configurations, the optimal driver for the purpose of generating waves within the heart in vivo. The second aim is to quantify the shear stiffness of normal myocardium throughout the cardiac cycle using MRE and to compare MRE stiffness to left ventricular chamber pressure in an in vivo pig model. MRE was performed in six pigs with six different driver setups, including no motion, three noninvasive drivers, and two invasive drivers. MRE wave displacement amplitudes were calculated for each driver. During the same MRI examination, left ventricular pressure and MRI-measured left ventricular volume were obtained, and MRE myocardial stiffness was calculated for 20 phases of the cardiac cycle. No discernible waves were imaged when no external motion was applied, and a single pneumatic drum driver produced higher amplitude waves than the other noninvasive drivers (P < 0.05). Pressure-volume loops overlaid onto stiffness-volume loops showed good visual agreement. Pressure and MRE measured effective stiffness showed good correlation (R(2) = 0.84). MRE shows potential as a noninvasive method for estimating effective myocardial stiffness throughout the cardiac cycle. PMID- 20578053 TI - Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytes. AB - Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5(-/-) mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5(-/-) mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. PMID- 20578054 TI - RIG-I mediates nonsegmented negative-sense RNA virus-induced inflammatory immune responses of primary human astrocytes. AB - While astrocytes produce key inflammatory mediators following exposure to neurotropic nonsegmented negative-sense RNA viruses such as rabies virus and measles virus, the mechanisms by which resident central nervous system (CNS) cells perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases including retinoic acid-inducible gene I (RIG I) have been described that function as intracellular sensors of replicative RNA viruses. Here, we demonstrate that primary human astrocytes constitutively express RIG-I and show that such expression is elevated following exposure to a model neurotropic RNA virus, vesicular stomatitis virus (VSV). Evidence for the functional nature of RIG-I expression in these cells comes from the observation that this molecule associates with its downstream effector molecule, interferon promoter stimulator-1, following VSV infection and from the finding that a specific ligand for RIG-I elicits astrocyte immune responses. Importantly, RIG-I knockdown significantly reduces inflammatory cytokine production by VSV-infected astrocytes and inhibits the production of soluble neurotoxic mediators by these cells. These findings directly implicate RIG-I in the initiation of inflammatory immune responses by human glial cells and provide a potential mechanism underlying the neuronal cell death associated with acute viral CNS infections. PMID- 20578056 TI - Multiphase pseudocontinuous arterial spin labeling (MP-PCASL) for robust quantification of cerebral blood flow. AB - Pseudocontinuous arterial spin labeling (PCASL) has been demonstrated to provide the sensitivity of the continuous arterial spin labeling method while overcoming many of the limitations of that method. Because the specification of the phases in the radiofrequency pulse train in PCASL defines the tag and control conditions of the flowing arterial blood, its tagging efficiency is sensitive to factors, such as off-resonance fields, that induce phase mismatches between the radiofrequency pulses and the flowing spins. As a result, the quantitative estimation of cerebral blood flow with PCASL can exhibit a significant amount of error when these factors are not taken into account. In this paper, the sources of the tagging efficiency loss are characterized and a novel PCASL method that utilizes multiple phase offsets is proposed to reduce the tagging efficiency loss in PCASL. Simulations are performed to evaluate the feasibility and the performance of the proposed method. Quantitative estimates of cerebral blood flow obtained with multiple phase offset PCASL are compared to estimates obtained with conventional PCASL and pulsed arterial spin labeling. Our results show that multiple phase offset PCASL provides robust cerebral blood flow quantification while retaining much of the sensitivity advantage of PCASL. PMID- 20578055 TI - Focal cerebral ischemia induces a multilineage cytogenic response from adult subventricular zone that is predominantly gliogenic. AB - The purpose of this study was to ascertain the relative contribution of neural stem/progenitor cells (NSPCs) of the subventricular zone (SVZ) to lineages that repopulate the injured striatum following focal ischemia. We utilized a tamoxifen inducible Cre/loxP system under control of the nestin promoter, which provides permanent YFP labeling of multipotent nestin(+) SVZ-NSPCs prior to ischemic injury and continued YFP expression in all subsequent progeny following stroke. YFP reporter expression was induced in adult male nestin-CreER(T2):R26R-YFP mice by tamoxifen administration (180 mg kg(-1), daily for 5 days). Fourteen days later, mice were subjected to 60-min transient middle cerebral artery occlusion (MCAO) and sacrificed at 2 days, 2 weeks, or 6 weeks post-MCAO for phenotypic fate mapping of YFP(+) cells using lineage-specific markers. Migration of YFP(+) cells from SVZ into the injured striatal parenchyma was apparent at 2 and 6 weeks, but not 2 days, post-MCAO. At 2 weeks post-MCAO, the average percent distribution of YFP(+) cells within the injured striatal parenchyma was as follows: 10% Dcx(+) neuroblasts, 15-20% oligodendrocyte progenitors, 59% GFAP(+) astrocytes, and only rare NeuN(+) postmitotic neurons. A similar phenotypic distribution was observed at 6 weeks, except for an increased average percentage of YFP(+) cells that expressed Dcx(+) (20%) or NeuN (5%). YFP(+) cells did not express endothelial markers, but displayed unique anatomical relationships with striatal vasculature. These results indicate that nestin(+) NSPCs within the SVZ mount a multilineage response to stroke that includes a gliogenic component more predominant than previously appreciated. PMID- 20578057 TI - Clinical evaluation of the NS1 antigen-capture ELISA for early diagnosis of dengue virus infection in Brazil. AB - The fact that the diagnosis of infection with dengue virus is usually made by detecting IgM antibodies during the convalescent phase of the disease interferes with disease management and, consequently, with reducing mortality rates. This study evaluated the sensitivity and specificity of detection of NS1 in samples of patients suspected of acute dengue virus infection in Brazil. The results were used to institute treatment and the sensitivity and specificity of detection of NS1 were compared to the results of detection of IgM, virus isolation, and RT PCR. Detection of NS1 yielded better results than RT-PCR and virus isolation. When considering IgM detection and RT-PCR positive results as "gold standards," the sensitivity and specificity of the NS1 assay were 95.9% and 81.1%, respectively. All patients enrolled in the study were treated promptly and had an uneventful course of the disease. The detection of NS1 provided better results than the diagnostic techniques used currently during the acute phase of disease (RT-PCR and virus isolation). Detection of NS1 is an important tool for the diagnosis of acute dengue infection, particularly in highly endemic areas, allowing for rapid treatment of patients and reduction of disease burden. PMID- 20578058 TI - Placentation in the pig visualized by eGFP fluorescence in eNOS over-expressing cloned transgenic swine. PMID- 20578059 TI - A synthetic future in reproduction and development? PMID- 20578062 TI - Allele-specific expression of the MAOA gene and X chromosome inactivation in in vitro produced bovine embryos. AB - During embryogenesis, one of the two X chromosomes is inactivated in embryos. The production of embryos in vitro may affect epigenetic mechanisms that could alter the expression of genes related to embryo development and X chromosome inactivation (XCI). The aim of this study was to understand XCI during in vitro, pre-implantation bovine embryo development by characterizing the allele-specific expression pattern of the X chromosome-linked gene, monoamine oxidase A (MAOA). Two pools of ten embryos, comprised of the 4-, 8- to 16-cell, morula, blastocyst, and expanded blastocyst stages, were collected. Total RNA from embryos was isolated, and the RT-PCR-RFLP technique was used to observe expression of the MAOA gene. The DNA amplicons were also sequenced using the dideoxy sequencing method. MAOA mRNA was detected, and allele-specific expression was identified in each pool of embryos. We showed the presence of both the maternal and paternal alleles in the 4-, 8- to 16-cell, blastocyst and expanded blastocyst embryos, but only the maternal allele was present in the morula stage. Therefore, we can affirm that the paternal X chromosome is totally inactivated at the morula stage and reactivated at the blastocyst stage. To our knowledge, this is the first report of allele-specific expression of an X-linked gene that is subject to XCI in in vitro bovine embryos from the 4-cell to expanded blastocyst stages. We have established a pattern of XCI in our in vitro embryo production system that can be useful as a marker to assist the development of new protocols for in vitro embryo production. PMID- 20578064 TI - Identification of testis-specific ubiquitin-conjugating enzyme in the ascidian Ciona intestinalis. AB - The ubiquitin-proteasome system is known to play a key role in fertilization in ascidians, sea urchins, and mammals. To obtain insights into the ubiquitin conjugating enzymes (Ube2) involved in reproductive systems, we systematically explored Ube2 enzymes expressed in the testis of the ascidian Ciona intestinalis. Here, we report cDNA cloning and characterization of a novel type of Ube2r (Ci0100152677) that is capable of making a thiolester bond with ubiquitin. Northern analysis, whole-mount in situ hybridization and immunocytochemistry indicate that this enzyme is exclusively expressed in the testis, mainly in the germ cells during the late stage of spermatogenesis, and is localized in the sperm head and tail, suggesting possible participation in fertilization or spermatogenesis/spermiogenesis. PMID- 20578063 TI - Epidermal growth factor (EGF) induces motility and upregulates MMP-9 and TIMP-1 in bovine trophoblast cells. AB - Differentiation and restricted invasion/migration of trophoblast cells are crucial for feto-maternal communication in the synepitheliochorial placenta of cattle. EGF is expressed in the bovine placenta and likely regulates these cell properties. As cell migration and motility rely on the degradation of extracellular matrix we hypothesize that EGF is involved in the regulation of the MMP-9/TIMP-1 balance and thus could influence trophoblast migration, tissue remodeling, and the release of the fetal membranes after parturition. The aim of this in vitro study was to examine EGF-mediated effects on cell motility, proliferation, and MMP-9 and TIMP-1 expression in cultured bovine trophoblast cells. We used a trophoblast cell line (F3) derived from bovine placentomes to examine the influence of EGF on MMP-9 and TIMP-1 expression by semiquantitative RT-PCR and MMP activity by zymography. Migration assays were performed using a Boyden chamber and cell motility was measured by time-lapse analyses. To identify the involved signaling cascades, phosphorylation of mitogen-activated protein kinase (MAPK) 42/44 and Akt was detected by Western blot. EGF treatment increased both the abundance of MMP-9 and TIMP-1 mRNAs and the proteolytic activity of MMP 9. Furthermore, EGF stimulated proliferation and migration of F3 cells. Addition of specific inhibitors of MAPK (PD98059) and/or PI3K (LY294002) activation abolished or reduced EGF-induced effects in all experiments. In conclusion, EGF mediated effects stimulate migration and proliferation of bovine trophoblast cells and may be involved in bovine placental tissue remodeling and postpartum release of fetal membranes. PMID- 20578061 TI - Regulation of the G2/M transition in rodent oocytes. AB - Regulation of maturation in meiotically competent mammalian oocytes is a complex process involving the carefully coordinated exchange of signals between the somatic and germ cell compartments of the ovarian follicle via paracrine and cell cell coupling pathways. This review highlights recent advances in our understanding of how such signaling controls both meiotic arrest and gonadotropin triggered meiotic resumption in competent oocytes and relates them to the historical context. Emphasis will be on rodent systems, where many of these new findings have taken place. A regulatory scheme is then proposed that integrates this information into an overall framework for meiotic regulation that demonstrates the complex interplay between different follicular compartments. PMID- 20578065 TI - Molecular dynamics of the blood-testis barrier components during murine spermatogenesis. AB - The blood-testis barrier (BTB) separates the seminiferous epithelium into the adluminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII-IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin-3, claudin-11, occludin, and zonula occludens-1 (ZO-1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII-IX). Although we detected claudin-11, occludin, and ZO-1 throughout spermatogenesis, claudin-3 was only detected during stages VI-IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II-VI, Middle: VII-VIII, Late: IX-I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage-specific localization of claudin-3 protein plays an important role in regulating BTB permeability. PMID- 20578066 TI - Characteristics of HIV-1 non-B subtype infections in Northwest Poland. AB - The number of non-B subtype HIV-1 infections in Europe has been increasing even though major regional differences have been observed. This trend was investigated in northwestern Poland using sequence and epidemiological data from a cohort of 102 HIV-1-infected patients from Szczecin, Poland. HIV-1 subtypes were defined by phylogenetic analysis of viral reverse transcriptase- and protease-partial coding regions, and results were compared with online subtyping by Standford and REGA tools. Subtype analysis using on-line subtyping methods produced varying results if compared to phylogenesis, with concordant variant assignment obtained for 98% (100/102) of sequences by Stanford and 85% (87/102) by REGA. In the population studied, non-B subtype infections comprised 21% of the infections and consisted of subtype D (57%, n = 12), CRF01_AE (19%, n = 4), A and C clades (9.5%, n = 2), and the CRF13_cpx recombinant isolate (4.8%, n = 1). Patients carrying non-B subtypes were predominantly heterosexuals with high percentage (57%) of women observed in the group. All HIV-1 non-B women were Caucasian with majority (83%) of infections acquired in Poland; however, among 12 travelers included in the study a higher proportion of non-B infections was noted (50%, P = 0.01). Moreover, lower baseline lymphocyte CD4 counts (P = 0.01), higher baseline HIV-1 viremia (P = 0.08), and a more advanced stage of the disease (P = 0.03) were observed among individuals infected with non-B subtypes. The data indicated that the proportion of HIV-1 non-B subtype infections was higher than previously reported in Poland consisting of a high subtype D prevalence. Furthermore, subtype D transmission occurred primarily between heterosexual Caucasian individuals from this region. PMID- 20578067 TI - Utilization of a second caregiver in the care of a child with a tracheostomy in the homecare setting. AB - OBJECTIVE: To safely discharge a child with a tracheostomy tube to home, we require two legal guardians/parents to complete a special training program. However, there are times when two parents/guardians are unavailable or unwilling to be trained. Therefore, the purpose of this study was to evaluate the role of the second caregiver of a child with a tracheostomy tube in the home setting. METHODS: A retrospective, descriptive, qualitative, pilot study of a convenience sample of parents of 16 children who were discharged from the hospital with a tracheostomy tube between September 2004 and December 2008 was conducted. Data were obtained from the unit's discharge database and from the primary and/or secondary caregivers. Univariate analyses were used to determine the frequency of primary and secondary caregiver participation at home. Themes were generated from caregiver responses regarding utilization of a second caregiver in the home. RESULTS: A majority (93.8%, n = 15) reported primary caregivers participating very often in the care of the infant at home; less than half (31.3%, n = 5) reported comparable secondary caregiver participation. Fifty percent (n = 8) said they would not be able to care for the infant at home without another trained caregiver. Analysis of the caregiver responses revealed three major themes: confidence, safety, and respite/support. CONCLUSION: Findings support the importance of training two caregivers in the care of a child being discharged with a tracheostomy tube. Training should include the medical/nursing care of the child as well as anticipatory guidance regarding what to expect and the need for respite services. PMID- 20578068 TI - 1H MRS of intramyocellular lipids in soleus muscle at 7 T: spectral simplification by using long echo times without water suppression. AB - The popular short echo time (1)H MR spectroscopy acquisition method for detection of intramyocellular lipids suffers from spectral overlap due to the large, broad, and asymmetric extramyocellular lipid signals, the time-consuming practice of selecting "lean" voxels for spectroscopy, and the overlap of the extramyocellular lipid signal with the creatine methyl (1)H signal at approximately 3 parts per million (ppm), commonly used as an internal standard. Using an alternative acquisition strategy, spectra with well-resolved intramyocellular lipids resonances were acquired from large volumes (10 to 15 mL) of human soleus muscle in less than 5 min by single-voxel 7-T (1)H MR spectroscopy, using an echo time of 280 ms. From the high-resolution spectra, an average intramyocellular lipid concentration of 7.7 +/- 3.5 mmol/kg muscle was found for 25 healthy subjects (male/female 17/8; age 29.4 +/- 6.6 years). Since water suppression was not required, the (1)H signals from unsaturated intracellular triglycerides at about 5.3 ppm were easily detected, which, in combination with the well-determined (CH(2))(n)-/CH(3) intensity ratio at long echo time, enabled assessment of the composition of triglycerides in the intramyocellular lipids compartment. Long echo single-voxel spectroscopy at 7 T offers rapid and convenient acquisition of high-resolution spectra from human soleus muscle. PMID- 20578070 TI - Object-based attention benefits reveal selective abnormalities of visual integration in autism. AB - A pervasive integration deficit could provide a powerful and elegant account of cognitive processing in autism spectrum disorders (ASD). However, in the case of visual Gestalt grouping, typically assessed by tasks that require participants explicitly to introspect on their own grouping perception, clear evidence for such a deficit remains elusive. To resolve this issue, we adopt an index of Gestalt grouping from the object-based attention literature that does not require participants to assess their own grouping perception. Children with ASD and mental- and chronological-age matched typically developing children (TD) performed speeded orientation discriminations of two diagonal lines. The lines were superimposed on circles that were either grouped together or segmented on the basis of color, proximity or these two dimensions in competition. The magnitude of performance benefits evident for grouped circles, relative to ungrouped circles, provided an index of grouping under various conditions. Children with ASD showed comparable grouping by proximity to the TD group, but reduced grouping by similarity. ASD seems characterized by a selective bias away from grouping by similarity combined with typical levels of grouping by proximity, rather than by a pervasive integration deficit. PMID- 20578069 TI - Association between depression and anxiety in high-functioning children with autism spectrum disorders and maternal mood symptoms. AB - Research suggests that children with autism spectrum disorders (ASDs) and their relatives have high rates of depression and anxiety. However, relatively few studies have looked at both factors concurrently. This study examined the potential relationship between maternal mood symptoms and depression and anxiety in their children with ASD. Participants were 31 10- to 17-year-old children with an ASD diagnosis that was supported by gold-standard measures and their biological mothers. Mothers completed the Autism Comorbidity Interview to determine whether the child with ASD met criteria for any depressive or anxiety diagnoses and a questionnaire of their own current mood symptoms. As expected, many children with ASD met criteria for lifetime diagnoses of depressive (32%) and anxiety disorders (39%). Mothers' report of their own current mood symptoms revealed averages within the normal range, though there was significant variability. Approximately 75% of children with ASD could be correctly classified as having a depressive or anxiety disorder history or not based on maternal symptoms of interpersonal sensitivity, hostility, phobic anxiety, depression, and anxiety. The results provide preliminary evidence that maternal mood symptoms may be related to depression and anxiety in their children with ASD. Although the design did not allow for testing of heritability per se, the familial transmission patterns were generally consistent with research in typical populations. While larger follow-up studies are needed, this research has implications for prevention and intervention efforts. PMID- 20578072 TI - High-grade neuroendocrine carcinoma of the lung shows increased thymidylate synthase expression compared to other histotypes. AB - BACKGROUND: Thymidylate synthase (TS) expression has been reported in various tumors, including non-small-cell lung carcinoma (NSCLC), but not in high-grade neuroendocrine (HGNE) carcinoma of the lung. METHODS: We measured TS expression in surgically resected pulmonary tumors, comparing HGNE carcinomas of the lung (13 large-cell neuroendocrine carcinomas, 8 small-cell lung carcinomas) with squamous cell carcinoma and adenocarcinoma of the lung using laser-capture microdissection for tissue isolation, real-time polymerase chain reaction (PCR), and immunohistochemistry. We also measured TS mRNA expression in small-cell lung carcinoma (SCLC) and NSCLC cell lines using real-time PCR. RESULTS: At both mRNA and protein levels, TS expression was significantly higher in squamous cell carcinoma compared to adenocarcinoma. Moreover, TS expression was significantly higher in HGNE carcinomas of the lung compared to squamous cell carcinoma. A significant correlation was found between mRNA and protein expression. TS mRNA expression in SCLC cell lines was significantly higher than in NSCLC cell lines. CONCLUSIONS: TS expression was higher in HGNE carcinomas of the lung than in squamous cell carcinoma, which was higher than in adenocarcinoma. This information may be useful in predicting the effects of TS-inhibiting agents in patients with NSCLC and HGNE carcinomas of the lung. PMID- 20578073 TI - Identifying risk factors for postoperative cardiovascular and respiratory complications after major oral cancer surgery. AB - BACKGROUND: Surgical resection of oral cancer can be associated with significant postoperative cardiovascular and respiratory complications that require more sensitive predictors. METHODS: All patients with oral squamous cell carcinoma treated from July 2005 to April 2008 were retrospectively reviewed. The Goldman Revised Cardiac Risk Index (GRCRI) was used to predict cardiovascular complications. Other evidence-based a priori predictors were applied in an h-fold cross-validation model. RESULTS: Operating room (OR) time was an independent predictor of cardiovascular complications (odds ratio = 1.54, p = .002, 95% confidence interval [CI] = 1.18-2.02) and respiratory complications (odds ratio = 1.3, p = .06, 95% CI = 0.99-1.64) after multivariate adjustment. OR time and estimated blood loss predicted cardiovascular complications with 73% sensitivity. The GRCRI achieved 37% sensitivity. OR time and tracheostomy predicted respiratory complications with 75% sensitivity. CONCLUSIONS: The GRCRI was not prognostic for cardiovascular complications in patients with oral cancer. The most sensitive predictors for cardiovascular complications were OR time and estimated blood loss; for respiratory complications they were OR time and tracheostomy. PMID- 20578074 TI - T1 and T2 hypopharyngeal cancer treatment with laser microsurgery. AB - BACKGROUND AND OBJECTIVE: To assess the oncologic results and functional outcomes of CO(2) laser microsurgery in T1 and T2 hypopharyngeal cancer. METHODS: The files of 119 T1 and T2 hypopharyngeal carcinoma cases primarily managed with laser surgery were reviewed. Cases were assessed for 5-year disease-specific survival (DSS) as well as local control (LC) rates, with respect to T and N classification, status of surgical margins, and decision on neck management and adjuvant therapy. Cases were additionally evaluated for incidence of major complications and retention of laryngeal and pharyngeal function. RESULTS: DSS and LC rates of 72.6% and 85.4%, respectively, were noted overall in this series. Survival rates were found to be significantly better for cases with negative surgical margins. The presence of regional metastases was also found to significantly affect prognosis. Satisfactory retention of function and a low rate of major complications were noted. CONCLUSION: Laser surgery appears to be very effective for T1 and T2 hypopharyngeal cancer treatment as long as clear surgical margins can be achieved. Oncologic results are acceptable with low incidence of complications and satisfactory retention of function. The neck must always be included in the primary treatment plan of hypopharyngeal lesions. PMID- 20578075 TI - Perioperative quality metrics for one step breast cancer surgery: a patient centered approach. AB - BACKGROUND AND OBJECTIVES: Patient-centered care is recommended by the Institute of Medicine to build a better healthcare system. The aim of this study was to audit patient-centered quality measures (QM) to create a breast center report card that could be provided to patients for education and informed consent. METHODS: An IRB approved retrospective review of 695 patients undergoing sentinel lymph node biopsy for breast cancer was conducted to audit the components of one step surgery and other QM. RESULTS: The intraoperative sensitivity to detect node positive patients was 25% (2/8), 27% (9/34), and 87% (68/78) for pN0(i+), pN1mi, pN1 patients, respectively. The re-excision lumpectomy rate was 15% (72/471) and the one step surgery success rate, which included lumpectomy and mastectomy patients, was 86% (598/695). Patient self-assessment of "very good to excellent" cosmesis and pain control were 77% (103/134) and 83% (60/72). Local recurrence rate was 2% (12/695) at a mean 3.1-year follow-up. CONCLUSIONS: The components of care that contribute to a patient-centered assessment of breast cancer surgery are measurable. "Bundling" of QM creates a perioperative report card that aids patients' informed consent and provides a framework for future comparative effectiveness studies. PMID- 20578076 TI - Oncological safety of skin sparing mastectomy followed by immediate reconstruction for locally advanced breast cancer. AB - BACKGROUND AND OBJECTIVES: Skin sparing mastectomy (SSM) has been demonstrated as an oncologically safe procedure for early breast cancer in several studies. But few studies concerned the safety of SSM for patients with locally advanced breast cancer; therefore, its safety for these patients is less clear. The purpose of this study is to examine the oncological safety of SSM followed by immediate reconstruction for locally advanced breast cancer. METHODS: We retrospectively analyzed 897 breast cancer patients who underwent mastectomy for stage IIB (T3N0) III between 1996 and 2005. Of 897, 87 underwent SSM (n = 73) or nipple sparing mastectomy (NSM, n = 14). We compared the local recurrence (LR) rate, disease free survival (DFS) and overall survival (OS) for SSM group with conventional mastectomy group. RESULTS: The 5-year DFS and OS of SSM group were not worse than those of CM group for all stages. LR rate was 3.0% (2/67) for IIB, 2.8% (1/36) for IIIA, 4.5% (1/22) for IIIC, and 5.0% (1/20) for T3 in SSM group. There was no difference in LR rates between SSM group and CM group for all stages. CONCLUSIONS: Our study demonstrates that SSM followed by immediate reconstruction is oncologically safe for locally advanced breast cancer. PMID- 20578077 TI - Kyphoplasty for spinal fractures from multiple myeloma. AB - INTRODUCTION: Vertebral destruction secondary to multiple myeloma is a significant clinical issue, and controversy still exists over how many levels should undergo kyphoplasty in multiple myeloma. In addition, in vertebrae that have lost wall integrity, cement extravasation remains an important consideration and is relatively contraindicated. METHODS: Forty-three symptomatic vertebral fractures from multiple myeloma were diagnosed by magnetic resonance imaging (MRI). In levels with anterior vertebral wall compromise, two distinct sequential applications of cement were performed. In levels with demonstrated posterior or lateral wall deficiency, cement was injected under fluoroscopy. RESULTS: All patients tolerated the procedure well and had immediate relief of back pain after kyphoplasty. Symptomatic cement extravasation and other complications were not observed. Vertebral height was restored (anterior 56.9 +/- 14.2% to 82.9 +/- 11.2%, middle 71.0 +/- 13.4% to 81.1 +/- 6.4%) (P < 0.001), and the mean kyphotic angle was improved (17.1 +/- 7.2 degrees to 8.9 +/- 6.4 degrees ) (P < 0.001). The mean VAS decreased significantly from presurgery to postsurgery (8.1 +/- 1.5 to 3.6 +/- 1.8) (P < 0.001), as did the ODI (63.2 +/- 15.9 to 37.1 +/- 10.2) (P < 0.001). Six of eight subscores measured by the SF-36, were significantly improved by the operation. All improvements were sustained up to final follow-up. CONCLUSION: Kyphoplasty is a safe and clinically effective treatment for pathologic vertebral fractures from multiple myeloma, even in levels with vertebral wall deficiency. The strategy of determining systematic level by alterations in MRI signal is effective in lowering the cost. PMID- 20578078 TI - Limb salvage surgery for calcaneal malignancy. AB - BACKGROUND: Advances in oncologic treatment modalities and wide resection have made limb salvage procedures in calcaneal malignancy increasingly possible. However, reconstructions of the calcaneal remain a major surgical challenge because of the rarity and specific anatomy of this condition. METHODS: we retrospectively reviewed five patients who had primary calcaneal malignancy and underwent total calcanectomy and reconstructions with the distally pedicled osteocutaneous folded fibular flap between 2001 and 2007. The diagnoses included chondrosarcoma in 2, Ewing's sarcoma in 2 and osteosarcoma in 1. Three tumors were classified as stage-II B lesions, one as I A and one as II A. Wide resection margins were achieved in all patients. The patients were followed up for a mean of 50.4 months (range, 32-76 months). Patients were examined clinically and radiographically and were assessed functionally with Musculoskeletal Tumor Society (MSTS) score and American Orthopaedic Foot and Ankle Society (AOFAS) score. RESULTS: Four patients had no evidence of disease, and lung metastasis was found in one patient who was alive with disease. No local recurrence occurred in this series. At latest evaluation four patients had no evident limp or limitation of daily activities and one patient had mild limp. The average MSTS 93 score and AOFAS score were 83.2% and 86.4% at the last follow-up, respectively. All fibular flaps survived and bone unions achieved successfully. Fibula hypertrophies were seen in three patients. The overall mean time for bone union was 6.2 months. The mean time to full weight-bearing was 8.6 months. The average two-point discrimination was 2.3 cm at the time of final follow-up. Two patients had surgery-related complications including hematoma in 1 and skin margin necrosis in 1. CONCLUSIONS: Following the wide resection of calcaneal malignancy, biological reconstruction using distally pedicled osteocutaneous fibular has proven to be a successful limb salvage procedure, offering satisfactory local tumor control and functional restoration of the lower extremity function. PMID- 20578079 TI - Management of gastric cancer in Ontario. AB - OBJECTIVE: To describe the processes of care for gastric cancer in Ontario and identify areas in which care and possibly survival can be improved. SUMMARY BACKGROUND DATA: Survival in North America is poor for patients with gastric cancer, with stage-matched survival markedly worse than is seen in Asian and European series. Few Western studies have examined processes of care associated with gastric cancer. METHODS: We identified all cases of gastric cancer in Ontario, Canada from April 1, 2000 to March 31, 2005, and describe the demographics of patients, staging of the cancer, treatment, and survival. RESULTS: In this series of 3,666 patients, 81% of cases had a CT scan performed prior to resection and 90% of cases received an upper endoscopy. We found that 55% of patients were treated palliatively and only 1,645 patients underwent a curative-intent resection. Among patients who did not receive a resection over 50% of the cases appeared to have had a diagnostic laparoscopy rather than a laparotomy. Survival was related to the type of resection performed, likely reflecting the extent of disease. Higher institution volume and age were related to improved survival for curative-intent cases. CONCLUSION: In this population based analysis, we found evidence of under-utilization of pre-operative radiology and endoscopy. Many patients were treated palliatively, reflecting presentation of the cancer at an advanced stage. For curative patients, survival was associated with age, surgical type, and resection in a higher volume institution. PMID- 20578080 TI - Clinicopathologic characteristics and prognosis of mucinous gastric carcinoma. AB - BACKGROUND AND OBJECTIVES: Reports of clinicopathological features and prognosis in patients with mucinous gastric carcinoma (MGC) are conflicting. The aim was to describe the clinicopathological features and prognosis of patients with MGC in comparison with nonmucinous gastric carcinoma (NMGC). METHODS: We reviewed the records of 1,278 consecutive patients diagnosed with gastric carcinoma who were resected surgically from 1993 to 2003. Among them, 48 patients (3.8%) with MGC were compared to 1,230 patients with NMGC. RESULTS: There were significant differences in tumor location, stage of disease, lymphatic invasion, and vascular invasion between the patients with MGC and NMGC. The overall 5-year survival of patients with MGC was 27.2% as compared with 42.8% for patients with NMGC (P = 0.031). For the patients with the same stage, there was no significant difference between MGC and NMGC. With respect to patients with MGC, multivariate analysis showed that lymph node metastasis and curative resection were significant factors affecting survival. CONCLUSIONS: MGC is rare and detected mostly in an advanced stage. Mucinous histology type itself is not an independent prognostic factor. PMID- 20578081 TI - Association of heparanase gene (HPSE-1) single nucleotide polymorphisms with gastric cancer. AB - BACKGROUND: Heparanase activity plays a decisive role in biological processes associated with remodeling of the extracellular matrix (e.g., cancer metastasis, angiogenesis, and inflammation). Heparanase gene overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the potential association between single nucleotide polymorphisms (SNPs) of the HPSE-1 gene, tumor susceptibility, clinicopathological parameters, and survival with gastric cancer among the Han population in northern China. METHODS: In this case-control study, there were 155 patients with gastric cancer and 204 healthy controls. The genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Chi-square test was performed to exam differences of genotypes or alleles frequency between samples. The effect of various variables on outcome was investigated by multivariate analysis using the Cox proportional hazards model. RESULTS: We identified four polymorphisms in the HPSE-1 gene. Polymorphisms in introns 2 and 3, exon8, and exon13 occurred at a minor allele frequency of >or=10%. There was an increase in frequency of individuals with a genotype that carried the intron3 (A), exon8 (A), exon13 (G) haplotype (AAG) in patients with gastric cancer compared with healthy individuals (P = 0.0001; OR = 7.467; 95% CI: 2.274-24.509). SNP rs11099592 variant genotypes AG/AA were associated with a Borrmann type classification (P = 0.015; OR = 0.182; 95% CI: 0.049-0.668) and invasion depth (P = 0.020; OR = 0.341; 95% CI: 0.134-0.866), whereas SNP rs4328905 AG genotype was correlated to Lauren diffuse grade (P = 0.027; OR = 0.419; 95% CI 0.191-0.917). SNP rs6856901 variant genotypes GC/CC were associated with a better tumor-related survival (P = 0.028; OR = 0.504; 95% CI: 0.273-0.930) compared with GG genotype. CONCLUSIONS: HPSE-1 polymorphisms may contribute to gastric tumor characteristics. SNP rs6856901 may be helpful in identifying clinical outcome of patients with gastric cancer. PMID- 20578082 TI - Pathological prognostic score as a simple criterion to predict outcome in gastric carcinoma. AB - PURPOSE: The aim of this study was to establish a simple criterion to predict prognosis of patients with gastric carcinoma. METHODS: Two hundred four patients with gastric carcinoma, who had been treated with curative resection, were enrolled. One point was added for each category among four pathological factors of depth of tumor, lymph node metastasis, venous invasion, and lymphatic invasion. Pathological Prognostic Score (PPS) was determined by an aggregate of these points for each category. RESULTS: There existed a significant difference between survivals of patients with PPS 0 or 1 and 2 or 3 (P = 0.0002). Similarly, there also existed a significant difference between survivals of patients with PPS 2 or 3 and 4 (P = 0.010). CONCLUSIONS: PPS can be quite simple criteria to predict prognosis of gastric carcinoma with a strict stratification. PMID- 20578083 TI - Assessment of open versus laparoscopy-assisted gastrectomy in lymph node-positive early gastric cancer: a retrospective cohort analysis. AB - BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is still limited for early gastric cancer (EGC) with low possibility of lymph node (LN) metastasis, due to the concern for incomplete LN dissection and controversial long-term outcomes. We assessed oncological outcomes of laparoscopy-assisted versus open gastrectomy (OG) for patients with LN positive EGC. METHODS: Between 2003 and 2007, 204 patients underwent surgery for LN positive EGC. We evaluated adequacy of LN dissection and early and long-term outcomes after OG (n = 162) and LAG (n = 42). RESULTS: Operative time was longer but hospital stay was shorter for LAG than OG. Postoperative complications occurred in 14 patients (8.6%) after OG and 1 patient (2.4%) after LAG (P = 0.316). Mean number of retrieved LNs and number of retrieved and metastatic LNs for each station did not differ between the two groups. During median 35 months of follow-up, 14 patients (8.6%) developed recurrence after OG, compared with 4 patients (9.5%) after LAG (P = 0.769). Overall 5-year disease-free survival was 89.9% and 89.7% after OG and LAG. Status of LN metastasis was the only independent prognostic factor for disease-free survival. CONCLUSIONS: LAG is an oncologically safe procedure even for LN positive EGC. Adequate LN dissection and comparable long-term outcomes to OG can be achieved by LAG. PMID- 20578084 TI - Case-matched analysis of totally laparoscopic versus open liver resection for HCC: short and middle term results. AB - BACKGROUND AND OBJECTIVES: Laparoscopy is gaining acceptance as a safe procedure for resection of liver neoplasms. The aim of this study is to evaluate surgical results and mid-term survival of minor hepatic resection performed for HCC. METHODS: Data of 16 patients with HCC, undergoing laparoscopic hepatectomy from September 2005 to January 2009, were compared to a control group of 16 patients who underwent open resection (OR) during the same period. The two groups were matched in terms of type of resection, tumor size, and severity of cirrhosis. RESULTS: One patient underwent conversion to an open approach. Laparoscopic approach resulted in shorter operating time (150 min, P:0.044) and lower blood loss (258 ml, P:0.008). There was no difference in perioperative morbidity and mortality rate; laparoscopic approach was associated with a shorter hospital stay (6.3 days, P:0.039). After a mean follow up of 32 months, disease free survival and overall survival were 40.2 and 23.3 months for laparoscopic group, and 47.7 and 31.4 months for OR group (P NS). CONCLUSION: Laparoscopic resection of HCC is feasible and safe in selected patients and can result in good surgical results, with similar outcomes in terms of overall and disease-free survival. PMID- 20578085 TI - Adjuvant chemoradiation therapy in gallbladder cancer. AB - BACKGROUND AND OBJECTIVES: Gallbladder cancer is a relatively uncommon gastrointestinal malignancy. Indications for adjuvant chemoradiation therapy after surgical resection have not yet been determined. We aimed this study to elucidate the effectiveness of adjuvant chemoradiation therapy according to TNM stage for gallbladder cancer. METHODS: Between March 2001 and March 2009, 100 patients with gallbladder cancer underwent surgical resection. We divided the patients according to TNM stage, and subdivided further according to whether adjuvant chemoradiation therapy was added or not. The clinicopathologic factors, recurrence and survival were retrospectively analyzed. RESULTS: Patients with gallbladder cancer at T2N0M0, T2N1M0, T3N0M0, and T3N1M0 stages were enrolled in this study. Among the four stages, the two lymph node-negative stages (T2N0M0 and T3N0M0) did not show any gain in survival by adding adjuvant chemoradiation therapy. Conversely, the remaining lymph node-positive stages (T2N1M0 and T3N1M0) showed gain in disease-free survival, and the lymph node-positive T2 stage (T2N1M0) showed gain in disease-specific survival. In patients with lymph node positive T2/T3 GB cancers, adjuvant chemoradiation therapy was an independent prognostic factor for survival. CONCLUSIONS: Adjuvant chemoradiation therapy is recommended for lymph node-positive T2/T3 gallbladder cancer following surgical resection. PMID- 20578087 TI - Disparities in cancer care between the United States of America and India and opportunities for surgeons to lead. AB - The recent report from International Agency for Research in Cancer (IARC) predicted a threefold increase in the global cancer burden by 2030 with a disproportionate rise in cases from the developing world countries such as India. The aim of this study is to compare the cancer care between the developed and developing countries such as the United States of America and India and suggest avenues for surgeons to take a lead in addressing these disparities. PMID- 20578086 TI - Intestinal complications after palliative treatment for asymptomatic patients with unresectable stage IV colorectal cancer. AB - BACKGROUND: The initial surgical management of asymptomatic patients with unresectable stage IV colorectal cancer (CRC) is still controversy. The aim of this study was to compare the incidence of major intestinal complications in asymptomatic patients who received palliative treatment for unresectable stage IV CRC, according to the type of treatment. METHODS: Between March 2001 and January 2008, we retrospectively analyzed 227 asymptomatic patients who underwent first line resection of the primary tumor followed by chemotherapy (144 patients, resection group) or those who underwent first-line chemotherapy (83 patients, chemotherapy group). RESULTS: In the resection group, the incidences of intestinal obstruction, peritonitis, fistula, and intestinal hemorrhage were 14.6%, 0%, 0.7%, and 4.8%, respectively. In the chemotherapy group, these incidences were 15.2%, 1.2%, 0%, and 3.5%, respectively. There were no significant differences between the two groups in terms of intestinal complications. In multivariate analysis of overall survival, treatment type (resection group vs. chemotherapy group) was not a significant prognostic factor (P = 0.076). CONCLUSIONS: In asymptomatic patients with unresectable stage IV CRC, first-line chemotherapy may be considered safe, with no increased risk of major intestinal complications compared with primary tumor resection plus chemotherapy. PMID- 20578088 TI - Correlation between hybrid capture II high-risk human papillomavirus DNA test chemiluminescence intensity from cervical samples with follow-up histologic results: a cytologic/histologic review of 367 cases. AB - BACKGROUND: The Hybrid Capture II high-risk human papillomavirus (hrHPV) DNA test is a US Food and Drug Administration-approved nucleic acid hybridization assay using chemiluminescence for the semiquantitative detection of hrHPV in cervical samples. Patient samples and controls are used to calculate results as negative for hrHPV if <1.0, positive for hrHPV if >2.5, and "equivocal" if between 1.0 and 2.5. METHODS: The authors reported on the cervical histologic results of 209 patients demonstrating "equivocal" results for hrHPV from SurePath (204 patients) or ThinPrep (5 patients) vials, and compared patients in this cohort with atypical squamous cells of undetermined significance (ASC-US) cytology on the index cervical Papanicolaou (Pap) test (Group 1; n = 148 patients) with a patient cohort demonstrating unequivocal positive hrHPV test results (Group 2; n = 148 patients). The chemiluminescence intensity of hrHPV tests from patients in Group 2 were correlated with the presence and severity of dysplasia on subsequent histologic results, and patients were thereby stratified for their subsequent risk of cervical intraepithelial neoplasia (CIN) types II/III. RESULTS: Approximately 97% of hrHPV tests demonstrating "equivocal" results were found to be positive at the time of retesting, and 15% of biopsied cases demonstrated CIN II or III. Results of follow-up histology after an ASC-US diagnosis, expressed as a percentage of the biopsied cohort, were: CIN II/III: 16.5% in Group 1 and 22.4% in Group 2; CIN I: 27% in Group 1 and 23.5% in Group 2; and negative: 56.5% in Group 1 and 54.1% in Group 2. Chemiluminescence intensity did not appear to be correlated with the severity of dysplasia. CONCLUSIONS: The percentage of high grade CIN in the "equivocal" hrHPV cohort is highly significant and therefore the management of these patients should be similar to the unequivocally positive population. After an unequivocal positive hrHPV test, the hrHPV chemiluminescence intensity does not appear to further predict the rate of high-grade CIN. PMID- 20578089 TI - Resequencing of pooled DNA for detecting disease associations with rare variants. AB - A combination of common and rare variants is thought to contribute to genetic susceptibility to complex diseases. Recently, next-generation sequencers have greatly lowered sequencing costs, providing an opportunity to identify rare disease variants in large genetic epidemiology studies. At present, it is still expensive and time consuming to resequence large number of individual genomes. However, given that next-generation sequencing technology can provide accurate estimates of allele frequencies from pooled DNA samples, it is possible to detect associations of rare variants using pooled DNA sequencing. Current statistical approaches to the analysis of associations with rare variants are not designed for use with pooled next-generation sequencing data. Hence, they may not be optimal in terms of both validity and power. Therefore, we propose here a new statistical procedure to analyze the output of pooled sequencing data. The test statistic can be computed rapidly, making it feasible to test the association of a large number of variants with disease. By simulation, we compare this approach to Fisher's exact test based either on pooled or individual genotypic data. Our results demonstrate that the proposed method provides good control of the Type I error rate, while yielding substantially higher power than Fisher's exact test using pooled genotypic data for testing rare variants, and has similar or higher power than that of Fisher's exact test using individual genotypic data. Our results also provide guidelines on how various parameters of the pooled sequencing design affect the efficiency of detecting associations. PMID- 20578090 TI - Distal stent delivery with Guideliner catheter: first in man experience. AB - Failure to deliver stents is one of the commonest causes of procedural failure in contemporary PCI practice. We describe successful use of the Guideliner catheter, the first purpose designed FDA and CE marked device delivery catheter in 13 complex cases in native coronary vessels and bypass grafts performed via the radial route to enable distal stent delivery following failure of conventional techniques. We discuss how the Guideliner catheter may be used to facilitate difficult radial cases. PMID- 20578091 TI - Decreasing operators' radiation exposure during coronary procedures: the transradial radiation protection board. AB - AIM: Transradial coronary procedures are associated with decreased vascular access site complications and other benefits compared to the femoral approach. There is some concern however about high-recorded radiation doses for interventional cardiologists using the transradial route. We therefore designed and investigated the effect of a transradial radiation protection board (TRPB) on operator radiation exposure during coronary procedures. METHODS AND RESULTS: One hundred and six patients were randomly assigned by time period to undergo radial coronary procedures either with or without a TRPB. This is a grooved arm board with a detachable 0.5-mm lead equivalent shield designed to rest between the patient's arm and side. Individual case-specific radiation exposures were measured using electronic personal dosimeter worn on the left outer pocket of the lead apron at chest level. The TRPB was used in addition to standard lead apron and thyroid shielding, below-table leaded flaps, and leaded glass. Operator radiation exposure was significantly decreased in the TRPB group overall: 28 [18 65] microSV versus 19.5 [10.5-35] microSV, P = 0.003. There were no significant differences in procedure duration, total fluoroscopy dose, or contrast load between the two groups. conclusion: Identification of methods to reduce operator radiation dose is important. The use of the TRPB can significantly reduce radiation exposure to radial operators. PMID- 20578092 TI - Preliminary results of the INSPIRE trial with the novel MGuard stent system containing a protection net to prevent distal embolization. AB - OBJECTIVE: To assess the efficacy of the MGuard(TM) stent combining a polymer mesh sleeve attached to the external surface of a bare-metal stent in preventing distal embolization during percutaneous coronary intervention (PCI). BACKGROUND: Distal embolization of thrombus/platelet aggregates is associated with worse immediate and long-term prognosis after PCI. Treatment of saphenous vein graft (SVG) and PCI in the setting of acute coronary syndromes (ACS) is often related to this complication. Although protection and aspiration devices have been shown to reduce distal embolization, they add time and cost to PCI. METHODS: A total of 30 patients were included. Inclusion criteria were de novo lesions in SVG or native vessels with angiographic evidence of instability with potential to provoke flow disturbances and/or distal embolization. Primary endpoint included the incidence of major adverse cardiac events (MACE) (composite of cardiac death, non-fatal myocardial infarction and TLR) up to 30 days of the procedure and TIMI flow right after the PCI. RESULTS: Mean population age was 60.8 years with 36.7% of diabetes. Overall, 53.3% presented with ACS, and most lesions were located in SVG (16 of 30). The majority of lesions had complex morphology including the presence of thrombus (30%) and ulcer (33.3%). The MGuard stent was successfully deployed in all cases with no angiographic/clinical complications including distal embolization. Final TIMI-3/blush-3 were achieved in all cases with no MACE up to 30 days of the procedure. CONCLUSIONS: In this preliminary evaluation, the MGuard device demonstrated excellent performance in a highly complex lesion subset, including absence of angiographic/procedural complications, and no adverse events up to 30-day FU. PMID- 20578093 TI - Failure of drug eluting stents presented as definite stent thrombosis. AB - BACKGROUND: Stent thrombosis (ST) risk may persist long after a successful drug eluting stents (DES) implantation. OBJECTIVE: We evaluated the incidence, timing, and clinical outcomes of patients with early (< or =30 days), late (>30-365 days), and very late (>365 days) angiographically proven ST related to DES. METHODS: Between 2004 and 2009, 4,396 patients underwent percutaneous coronary interventions (PCI) with DES implantations. This 5-year follow-up study included 38 patients (mean age 60 +/- 12 years; 76% males) who were readmitted with confirmed ST diagnoses. Clopidogrel therapy was prescribed for 3-12 months. Clinical follow-ups were conducted at 1 and 6 months following ST events. RESULTS: The overall ST rate was 0.9% (38/4,396); the late ST rate was 0.7%. There were four (11%) early and 34 (89%) late events; the time interval to thrombosis was 21 +/- 14 months (range 0.13-60 months). Two patients had stent fractures associated with ST, 37% had diabetes, and 68% presented with ST elevation myocardial infarctions (MI). One third was treated with clopidogrel at the ST event. Three patients (8%) had recurrent late ST events and two died within 1 month after the ST event (5%). At 6 months, we observed a 26% major adverse cardiac event rate, and the overall cardiac mortality rate was 8%. CONCLUSIONS: In our series, ST occurred infrequently (0.9%), mostly between 1 and 3 years after the period recommended for dual anti-platelet pharmacotherapy, and it is associated with substantial clinical consequences. PMID- 20578094 TI - Ischemic cardiac complications following G-CSF. AB - Granulocyte-colony stimulating factor (G-CSF) is commonly used in bone marrow transplant donors to increase the number of circulating progenitor cells. G-CSF has also been studied following myocardial infarction, but concern has been raised about the risks of G-CSF administration in patients with coronary artery disease. We present two cases of ischemic cardiac complications that are likely to be related to administration of G-CSF and provide a contemporary overview of the literature on the cardiovascular risks of G-CSF. PMID- 20578095 TI - Coronary guidewire circumcision during use of a Gopher support catheter: potential adverse interaction with polymer-jacketed wire design. AB - Support catheters with a threaded, distal tip may be useful for crossing recalcitrant coronary lesions. The interaction between the Gopher support catheter and polymer-coated coronary guidewires may, however, result in circumferential stripping of polymer from the guidewire, with resulting wire damage or fracture. We report two cases of polymer-coated guidewire damage with use of a Gopher support catheter, suggesting that these two devices should not be used together. PMID- 20578096 TI - Incidence of stroke in patients with d-transposition of the great arteries that undergo balloon atrial septostomy in the University Healthsystem Consortium Clinical Data Base/Resource Manager. AB - OBJECTIVES: The aim of this study was to investigate the incidence of stoke in pediatric patients undergoing a balloon atrial septostomy (BAS). BACKGROUND: Newborn infants with d-transposition of the great arteries (dTGA) can be compromised from significant hypoxemia due to inadequate mixing at the atrial level. BAS can be lifesaving by improving the intra-atrial mixing. BAS, although life-saving, is associated with risks including arrhythmias, infection, bleeding, stroke, or death. Recent studies have conflicting conclusions demonstrating the risk of BAS and brain injury using magnetic resonance imaging. However, these studies did not demonstrate the clinical significance of brain injury through physical manifestations of stroke. METHODS: The University HealthSystem Consortium Clinical Data Base/Resource Manager (UHC CDB/RM) consists of 103 Academic Medical Centers, and affiliated institutions. The CDB/RM was queried using billing codes upon discharge from the consortium hospitals from 2004 to 2008. RESULTS: In total, the UHC CDB/RM contained information on 1,295 neonatal patients (group 1) who were discharged with a diagnosis of dTGA, of which 440 had a BAS during the same hospitalization. In group 1, 18 had a coded diagnosis of stroke and only six of these 18 had a BAS. In group 2 (pediatric patients with dTGA), 952 patients were discharged with a diagnosis of dTGA, of which 37 had BAS. Pediatric patients (19 of 952) had a stroke and none of them had a BAS. CONCLUSIONS: In over 2,000 cases of dTGA reported in the CDB/RM over a 4-year period, BAS was not associated with an increased risk of clinical stroke either in the neonatal period or in follow-up hospitalizations. PMID- 20578097 TI - Percutaneous closure of multiple defects of the atrial septum: procedural results and long-term follow-up. AB - BACKGROUND: The percutaneous closure of single atrial septal defect (ASD) is a valid alternative to surgery. OBJECTIVES: To assess the feasibility of percutaneous treatment of multiple ASDs. METHODS: Between 1998 and 2007, 165 out of 1280 consecutive patients undergoing ASD percutaneous closure at our institution showed multiple defects that were classified in four categories: double atrial septal defects (d-ASD), multifenestrated atrial septal defects (f ASD), multifenestrated defects with no signs of right heart overload (f-PFO), and complex cases (c-ASD). The following end points were taken into consideration: (1) immediate procedural success; (2) long term safety and efficacy. In this study, up to 81% of multiple ASDs were suitable for percutaneous closure. RESULTS: Multiple device implantations were required in 47% of cases, especially in patients with d-ASD and c-ASD. Complication rate, residual shunt, and long term outcome were comparable among the four different categories. In particular, at long term follow-up (6 +/- 2 years) no patient required further surgical or percutaneous treatment and complete closure was confirmed in 99% of cases. CONCLUSIONS: Percutaneous closure of multiple ASDs is feasible and associated with a good outcome. A thorough identification and analysis of morphological aspects are mandatory in order to select the appropriate device and the optimal strategy. PMID- 20578098 TI - Late aortic perforation with an Atriasept device resulting in life-threatening tamponade. AB - Patients with compelling evidence of cryptogenic stroke due to patent foreamen ovale (PFO) are increasingly likely to be offered percutaneous closure of the defect. With improvements in technique there is now a high procedural success rate with low rates of periprocedural complications. Late complications are also rare, but include late perforation of the aortic root, which is rapidly progressive and potentially fatal. This has lead to the development of lower profile devices, which aim to reduce the risk of both early and late complications. At this stage, it is not clear if lower profile devices have safety profiles which are superior to the more established devices. We report the first case of late perforation of the aortic sinus by the lower profile Atriasept (Cardia) device presenting as life threatening cardiac tamponade in an adult who previously underwent percutaneous PFO closure. PMID- 20578099 TI - Cardiac shunt calculations made easy: a case-based approach. AB - On the basis of an interesting case of a 40-year-old lady with an atrial septal defect, we describe a simple approach for complex shunt volume calculations based on the Fick principle using hemodynamic data obtained in the catheterization laboratory. Understanding Fick's principle allows determination of all relevant flows, flow ratio, and resistances without having to resort to memorization of complex formulae. Those findings significantly impact the managements of patients like ours with hemodynamically and clinically relevant shunting. PMID- 20578101 TI - Transcatheter aortic valve implantation through the left subclavian artery with a patent LIMA graft. AB - We report the case of an 80-year-old male with severe aortic valve stenosis previously submitted to surgical myocardial revascularization with patent mammary graft treated by TAVI through left-transaxillary approach because of unsuitable transfemoral and transapical approaches. PMID- 20578100 TI - Management of residual shunts after initial percutaneous patent foramen ovale closure: a single center experience with immediate and long-term follow-up. AB - BACKGROUND: Moderate-to-large residual shunts following percutaneous patent foramen ovale (PFO) closure are clinically important and associated with recurrent neuroembolic events. However, their management has not been clearly established in clinical practice. We report our experience in patients of these patients with a prior history of cryptogenic stroke and/or transient ischemic attack (TIA). METHODS: All patients undergoing percutaneous PFO closure were routinely screened at six-months for residual shunts using transthoracic 2D echocardiography with antecubital administration of agitated saline contrast and color flow Doppler. Patients with evidence of moderate-to-large residual shunts were selected to undergo reintervention with shunt closure. Post-reintervention follow-up was performed at 24-hr, 30 days, and every six months thereafter. Clinical predictors of the moderate-to-large residual shunts, and the feasibility, safety and long-term efficacy of percutaneous residual shunt closure using a second device implant were examined. RESULTS: Between 1995 and 2007, a total of 424 patients underwent PFO closure. Of these, 5% (21/424) had moderate to-large residual shunts. Baseline characteristics among patients with moderate to-large residual shunts and those with only none or small defects (n = 403) were similar. Multivariate analysis identified the 24-hr postprocedure shunt as the only independent predictor of residual shunting at six months. Of the 21 study patients with moderate-to-large residual shunt (mean age, 47 +/- 14), one underwent successful elective surgical repair, while the remaining 20 underwent transcatheter closure using a second device. The technique was successful in 95% (19/20), and all but one patient had complete shunt closure at six months of their percutaneous reintervention. We report no deaths, recurrent strokes or TIAs during the long-term mean follow-up period of 2.9 years. CONCLUSIONS: Our study suggests that in patients with moderate-to-large residual PFO shunts, percutaneous reintervention using a second device implant is safe and effective. PMID- 20578102 TI - Atrial myxomas and coronary angiography. AB - Coronary angiography is not an only important component of preoperative evaluation of the patient with underlying coronary artery disease but also diagnostic tool for delineating cardiac myxomas. This also serve as an important surgical anatomical marker. We present two cases which presented with repeated episode of chest pain, were found to have atrial blushing on coronary angiography subsequent confirmation of diagnosis of atrial myxoma on echocardiography. PMID- 20578103 TI - On the loss of the phosphorylcholine-based DES coating on the abluminal surface of Endeavor stents. PMID- 20578104 TI - Inhibition of uPAR and uPA reduces invasion in papillary thyroid carcinoma cells. AB - OBJECTIVES/HYPOTHESIS: We analyzed the expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) in papillary thyroid carcinoma (PTC) and normal thyroid tissue and examined in vitro how uPA and uPAR contribute to an invasive/metastatic phenotype, and the functional consequences of inhibiting this system. STUDY DESIGN: Retrospective chart review of PTC patients, followed by prospective study using previously obtained patient tissue and PTC cellular models. METHODS: uPA and uPAR RNA and protein levels were analyzed in PTC patient tissue samples, PTC and normal thyroid tissue culture cells, and conditioned media (CM) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and/or Western blotting. The plasminogen-activating ability of CM was examined using dark-quenched casein fluorimetry and casein-plasminogen gel zymography. The invasive potentials of the PTC and normal thyroid epithelial cell lines were assessed using an in vitro cellular invasion/migration system. RESULTS: uPA and uPAR RNA and protein levels were increased in PTC patient samples and PTC cells relative to controls. uPA and uPAR RNA were also significantly higher in patients with metastatic disease. Casein-plasminogen zymography and Western blotting demonstrated increased active uPA secreted by PTC cells compared with normal thyroid cells. Fluorimetric assays revealed that the PTC cells' CM was able to activate plasminogen, resulting in measurable casein hydrolysis. This casein hydrolysis was prevented by the addition of several specific uPA inhibitors. Finally, the in vitro invasion phenotypes of PTC cells were augmented by the addition of plasminogen, and this augmentation was reversed by inhibitory anti-uPA and anti-uPAR antibodies. CONCLUSIONS: These data provide new functional evidence of the uPA/uPAR system's role in PTC invasion/metastasis and demonstrate the attractiveness of uPA and uPAR as molecular biomarkers and therapeutic targets. PMID- 20578105 TI - Evaluation of the effectiveness of airway fluoroscopy in diagnosing patients with laryngomalacia. AB - OBJECTIVES/HYPOTHESIS: To re-evaluate the usefulness of airway fluoroscopy (AF) in diagnosing laryngomalacia and to determine the effectiveness of AF in diagnosing laryngomalacia depending on the specific lesion. STUDY DESIGN: Retrospective chart review. METHODS: Patients from 0 to 12 months of age who presented with stridor were evaluated. Those who underwent AF and flexible fiberoptic laryngoscopy (FFL) and/or direct laryngoscopy (DL) were included in the study. The diagnosis made through AF, FFL, and/or DL were recorded with those considered definitive made through FFL and/or DL. The sensitivity, specificity, positive predictive value, and negative predictive value of AF compared to FFL and DL were calculated. The sensitivity, specificity, positive predictive value, and negative predictive value of AF with regard to specific sites of laryngeal collapse were calculated. RESULTS: AF showed an inconsistent sensitivity, specificity, and positive and negative predictive value compared to FFL and DL with regard to specific lesions. AF had an overall sensitivity of 35%, specificity of 67%, positive predictive value of 78%, and negative predictive value of 23% when compared to FFL in diagnosing laryngomalacia. When compared to DL, AF had an overall sensitivity of 44%, specificity of 60%, positive predictive value of 67%, and negative predictive value of 38% when diagnosing laryngomalacia. CONCLUSIONS: AF is a commonly used modality in the diagnostic workup of a patient with stridor. The effectiveness of AF is limited when compared to endoscopy when used for the evaluation of laryngomalacia. PMID- 20578107 TI - Approaches to spectral imaging hardware. AB - Instruments used for spectral, multispectral, and hyperspectral imaging in the biosciences have evolved significantly over the last 15 years. However, very few are calibrated and have had their performance validated. Now that spectral imaging systems are appearing in clinics and pathology laboratories, there is a growing need for calibration and validation according to universal standards. In addition, some systems produce spectral artifacts that, at the very least, challenge data integrity if left unrecognized. This unit includes a comparison of the band-pass and light-transmission characteristics of electronic tunable filters, interferometers, and wavelength-dispersive spectral imaging instruments, as well as a description of how they work. Methods are described to test wavelength accuracy and perform radiometric calibration. A real-life example of spectral artifacts is dissected in detail in order to show how to detect, diagnose, verify, and work around their presence when they cannot be eliminated. PMID- 20578106 TI - Web-based analysis and publication of flow cytometry experiments. AB - Cytobank is a Web-based application for storage, analysis, and sharing of flow cytometry experiments. Researchers use a Web browser to log in and use a wide range of tools developed for basic and advanced flow cytometry. In addition to providing access to standard cytometry tools from any computer, Cytobank creates a platform and community for developing new analysis and publication tools. Figure layouts created on Cytobank are designed to allow transparent access to the underlying experiment annotation and data processing steps. Since all flow cytometry files and analysis data are stored on a central server, experiments and figures can be viewed or edited by anyone with the proper permission, from any computer with Internet access. Once a primary researcher has performed the initial analysis of the data, collaborators can engage in experiment analysis and make their own figure layouts using the gated, compensated experiment files. Cytobank is available to the scientific community at http://www.cytobank.org. PMID- 20578109 TI - Detection of intracellular glutathione using ThiolTracker violet stain and fluorescence microscopy. AB - Glutathione plays an important role in protecting mammalian cells from oxidative stress and cell death. Because reduced glutathione (GSH) represents the large majority of intracellular free thiols, cell-permeant, thiol-reactive fluorescent probes represent potentially useful indicators of intracellular GSH. The ThiolTracker Violet stain (a registered trademark of Invitrogen) is a bright fluorescent probe that is highly reactive to thiols and can be used as a convenient and effective indicator of intracellular GSH and general redox status by a variety of detection modalities. While this probe has been validated in flow cytometry and microplate fluorimetry assays, the following method will describe details on the use of the ThiolTracker Violet dye in traditional fluorescence microscopy, as well as high-content imaging and analysis. PMID- 20578108 TI - Amine-reactive dyes for dead cell discrimination in fixed samples. AB - Amine-reactive dyes, also known as LIVE/DEAD fixable dead cell stains, are a class of viability dyes suitable for identifying dead cells in samples that will be fixed. These dyes cross the cell membranes of dead cells, and react with free amines in the cytoplasm. Live cells exclude these dyes because their cell membranes are intact, and free dye is washed away after staining. Notably, the reaction is irreversible; therefore, when cells are fixed and permeabilized (as with intracellular staining procedures), the bound dye remains associated with the dead cells (unlike other viability dyes). Since amine-reactive dyes are fluorescent when excited by lasers, dead cells can be identified by flow cytometry. This unit describes procedures, troubleshooting, and outcomes for using the two most commonly used amine-reactive dyes, ViViD and Aqua Blue. PMID- 20578110 TI - Volatile compounds with characteristic odour in moso-bamboo stems (Phyllostachys pubescens Mazel ex Houz. De ehaie). AB - INTRODUCTION: Moso-bamboo (Phyllostachys pubescens) is well known as an edible shoot in Asia, and the stems of moso-bamboo are used as tableware due to its characteristic odour. Despite the pleasant odour of bamboo stems, no detailed analysis of the volatile compounds has been reported. OBJECTIVE: To clarify the potent odourants contributing to the characteristic aroma of the bamboo, the aroma extract dilution analysis (AEDA) method was performed through gas chromatography olfactometry (GC-O) analysis. In addition, relative flavour activity (RFA) was calculated, in which both the flavor dilution (FD) factor and weight percentage of each compound are involved. RESULTS: Eighty-nine compound in bamboo stems oil were identified by GC and GC-MS. The main components of the oil were palmitic acid (16.5%), (E)-nerolidol (10.2%) and indole (8.1%). In sensory analysis, 18 aroma-active compounds were detected by aroma extract dilution analysis (AEDA). The most intense aroma-active compounds were eugenol (sweet, clove-like, green) and (E)-2-nonenal (green). CONCLUSION: The results of the sniffing test, RFA and FD factor indicated that (E)-2-nonenal and eugenol were estimated to have a bamboo-like aroma, and aldehyde compounds, such as a phenylacetaldehyde (floral) and C9-C10 unsaturated aldehydes, make the aroma of bamboo. PMID- 20578111 TI - Revealing the role of anchoring groups in the electrical conduction through single-molecule junctions. AB - A combined experimental and theoretical study is presented revealing the influence of metal-molecule coupling on electronic transport through single molecule junctions. Transport experiments through tolane molecules attached to gold electrodes via thiol, nitro, and cyano anchoring groups are performed. By fitting the experimental current-voltage characteristics to a single-level tunneling model, we extract both the position of the molecular orbital closest to the Fermi energy and the strength of the metal-molecule coupling. The values found for these parameters are rationalized with the help of density-functional theory-based transport calculations. In particular, these calculations show that the anchoring groups determine the junction conductance by controlling not only the strength of the coupling to the metal but also the position of the relevant molecular energy levels. PMID- 20578112 TI - Kinase-actuated immunoaggregation of Peptide-conjugated gold nanoparticles. PMID- 20578113 TI - New confinement method for the formation of highly aligned and densely packed single-walled carbon nanotube monolayers. PMID- 20578114 TI - Subcompartmentalized polymer hydrogel capsules with selectively degradable carriers and subunits. AB - Subcompartmentalized hydrogel capsules (SHCs) with selectively degradable carriers and subunits are designed for potential applications in drug delivery and microencapsulated biocatalysis. Thiolated poly(methacrylic acid) and poly(N vinyl pyrrolidone) are used to assemble 3-microm-diameter carrier capsules and 300-nm-diameter subunits, independently stabilized by a diverse range of covalent linkages. This paper presents examples of SHCs with tens of subcompartments and their successful drug loading, as well as selective degradation of the SHC carrier and/or subunits in response to multiple chemical stimuli. PMID- 20578115 TI - Out-of-plane magnetic patterning based on indentation-induced nanocrystallization of a metallic glass. AB - Periodic arrays of micrometer-sized ferromagnetic structures with perpendicular magnetic anisotropy are prepared by nanoindentation at the surface of a Fe(67.7)B(20)Cr(12)Nb(0.3) glassy ribbon initially showing in-plane magnetic anisotropy. The indented regions exhibit enhanced coercivity and saturation magnetization with respect to the surrounding nondeformed matrix. These effects are due to a mechanically driven selective nanocrystallization of the metallic glass, induced by nanoindentation, even without the need for thermal annealing. In addition, while the amorphous matrix becomes paramagnetic above 325 K, the crystallized regions (consisting of alpha-Fe) remain ferromagnetic upon heating to high temperatures. The local change in the magnetic anisotropy direction is ascribed to a certain degree of crystallographic texture, together with the inverse magnetostriction effect caused by the compressive indentation stresses. PMID- 20578116 TI - Uniform beads with controllable pore sizes for biomedical applications. PMID- 20578117 TI - Light-responsive molecular recognition and adhesion of vesicles. PMID- 20578118 TI - Lysine acetylation: the tale of a modification from transcription regulation to metabolism. PMID- 20578119 TI - Study of carbon monoxide oxidation on mesoporous platinum. AB - H(1) mesoporous platinum surfaces formed by electrodeposition from lyotropic liquid crystalline templates have high electroactive surface areas (up to 60 m(2) g(-1)) provided by the concave surface within their narrow (~2 nm diameter) pores. In this respect, they are fundamentally different from the flat surfaces of ordinary Pt electrodes or the convex surfaces of high-surface-area Pt nanoparticles. Cyclic voltammetry of H(1) mesoporous Pt films in acid solution is identical to that for polycrystalline Pt, suggesting that the surfaces of the pores are made up of low-index Pt faces. In contrast, CO stripping voltammetry on H(1) mesoporous Pt is significantly different from the corresponding voltammetry on polycrystalline Pt and shows a clear prewave for CO oxidation and the oxidation CO at lower overpotential. These differences in CO stripping are related to the presence of trough sites where the low-index Pt faces that make up the concave surface of the pore walls meet. PMID- 20578120 TI - Manganese acetate in pyrrolidinium ionic liquid as a robust and efficient catalytic system for epoxidation of aliphatic terminal alkenes. PMID- 20578121 TI - Toxicological evaluation of fucoidan from Undaria pinnatifidain vitro and in vivo. AB - The potential toxicity of fucoidan from Undaria pinnatifida was investigated in vitro and in vivo. By the Ames test, fucoidan showed no mutagenicity up to 500 microL/plate, and inhibited the mutagenicity induced by 4-nitro-quinoline-1 oxide, by up to 71%, compared with controls. In the bone marrow micronucleus test, fucoidan, at all levels tested, did not change the micronucleated polychromatic erythrocyte percentage ratio in mouse bone marrow cells. As an acute in vivo toxicity test, fucoidan from 0 to 2000 mg/kg body weight per day was administered orally to Sprague-Dawley rats for 28 days. No significant toxicological change was induced by fucoidan treatment up to 1000 mg/kg body weight per day in biochemical analyses, hematological analyses, necropsy and liver histopathology. The plasma ALT level was slightly, but significantly, increased in male rats at 2000 mg/kg/day. The consumption of fucoidan from Undaria pinnatifida, up to 1000 mg/kg body weight per day, may be safe in rodents, with no sign of toxicity after up to 28 days of daily administration. PMID- 20578122 TI - The development of artemisinin resistance in malaria: reasons and solutions. AB - Despite world-wide efforts in fighting malaria, this mosquito-borne infectious disease is a huge burden for the population, especially in tropical and subtropical areas. The WHO recommends artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria. However, artemisinin resistance cannot now be ignored. Factors affecting the development of artemisinin resistance include uncontrolled use of artemisinin-based combination therapy (ACT), mobile populations and migrants, artemisinin monotherapy, the use of subtherapeutic levels of artesiminin, substandard and counterfeit drugs, high treatment cost, and co-use of artemisinin derivates as prophylactic agents. Promising herbal alternatives are already in the pipeline, but the only long-term solution for eradicating malaria would be the development of a successful vaccination. PMID- 20578123 TI - Nanoscale imaging of the interface dynamics in polymer blends by femtosecond pump probe confocal microscopy. PMID- 20578124 TI - The 40th anniversary of the National Institute on Alcoholism and Alcohol Abuse: the impact on liver disease. PMID- 20578125 TI - To TWEAK, or not to TWEAK: that is the question. PMID- 20578126 TI - In vivo proliferation of hepadnavirus-infected hepatocytes induces loss of covalently closed circular DNA in mice. AB - Chronic hepatitis B virus (HBV) infection is maintained by the presence of covalently closed circular DNA (cccDNA), the template of viral transcription and replication. In quiescent hepatocytes, cccDNA is a stable molecule that can persist throughout the hepatocyte lifespan. However, in chronic HBV infection, immunomediated cell injury and compensatory hepatocyte proliferation may favor cccDNA decline and selection of cccDNA-free cells. To investigate the impact of liver regeneration on cccDNA stability and activity in vivo, we used the urokinase-type plasminogen activator (uPA)/severe combined immunodeficiency (SCID) mouse model. Primary tupaia hepatocytes (PTHs) chronically infected with woolly monkey HBV (WM-HBV) were isolated from one highly viremic uPA/SCID chimeric mouse and transplanted into 20 uPA recipients. Expansion of transplanted PTHs and viral load changes were determined by real-time polymerase chain reaction and immunohistochemistry. Transplantation of WM-HBV infected hepatocytes led to an average of 3.8 PTH doublings within 80 days, 75% reduction of virion productivity (relaxed circular DNA/cccDNA), and lower expression levels of pregenomic RNA and hepatitis B core antigen. Remarkably, a median 2-log decline of cccDNA per cell determined during PTH proliferation was due to both dilution of the cccDNA pool among daughter cells and a 0.5-log loss of intrahepatic cccDNA loads (P = 0.02). Intrahepatic viral DNA sequences persisting at the end of the study were mostly present as replicative intermediates and not as integrated virus. CONCLUSION: Cell division in the setting of liver regeneration and without administration of antiviral drugs induced strong destabilization of the cccDNA reservoir, resulting in cccDNA clearance in the great majority of chronically infected hepatocytes. PMID- 20578127 TI - Comparison of surrogate and direct measurement of insulin resistance in chronic hepatitis C virus infection: impact of obesity and ethnicity. AB - Studies using surrogate estimates show high prevalence of insulin resistance in hepatitis C infection. This study prospectively evaluated the correlation between surrogate and directly measured estimates of insulin resistance and the impact of obesity and ethnicity on this relationship. Eighty-six nondiabetic, noncirrhotic patients with hepatitis C virus (age = 48 +/- 7 years, 74% male, 44% white, 22% African American, 26% Latino, 70% genotype 1) were categorized into normal-weight (body mass index [BMI] < 25, n = 30), overweight (BMI = 25-29.9, n = 38), and obese (BMI > or = 30, n = 18). Insulin-mediated glucose uptake was measured by steady-state plasma glucose (SSPG) concentration during a 240-minute insulin suppression test. Surrogate estimates included: fasting glucose and insulin, glucose/insulin, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), insulin (I-AUC) and glucose (G-AUC) area under the curve during oral glucose tolerance test, and the Belfiore and Stumvoll indexes. All surrogate estimates correlated with SSPG, but the magnitude of correlation varied (r = 0.30-0.64). The correlation coefficients were highest in the obese. I-AUC had the highest correlation among all ethnic and weight groups (r = 0.57-0.77). HOMA-IR accounted for only 15% of variability in SSPG in the normal weight group. The common HOMA-IR cutoff of < or =3 to define insulin resistance had high misclassification rates especially in the overweight group independent of ethnicity. HOMA-IR > 4 had the lowest misclassification rate (75% sensitivity, 88% specificity). Repeat HOMA-IR measurements had higher within person variation in the obese (standard deviation = 0.77 higher than normal weight, 95% confidence interval = 0.25-1.30, P = 0.005). CONCLUSION: Because of limitations of surrogate estimates, caution should be used in interpreting data evaluating insulin resistance especially in nonobese, nondiabetic patients with HCV. PMID- 20578128 TI - Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection. AB - Oxidative stress has been identified as a key mechanism of hepatitis C virus (HCV)-induced pathogenesis. Studies have suggested that HCV increases the generation of hydroxyl radical and peroxynitrite close to the cell nucleus, inflicting DNA damage, but the source of reactive oxygen species (ROS) remains incompletely characterized. We hypothesized that HCV increases the generation of superoxide and hydrogen peroxide close to the hepatocyte nucleus and that this source of ROS is reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase 4 (Nox4). Huh7 human hepatoma cells and telomerase-reconstituted primary human hepatocytes, transfected or infected with virus-producing HCV strains of genotypes 2a and 1b, were examined for messenger RNA (mRNA), protein, and subcellular localization of Nox proteins along with the human liver. We found that genotype 2a HCV induced persistent elevations of Nox1 and Nox4 mRNA and proteins in Huh7 cells. HCV genotype 1b likewise elevated the levels of Nox1 and Nox4 in telomerase-reconstituted primary human hepatocytes. Furthermore, Nox1 and Nox4 proteins were increased in HCV-infected human liver versus uninfected liver samples. Unlike Nox1, Nox4 was prominent in the nuclear compartment of these cells as well as the human liver, particularly in the presence of HCV. HCV induced ROS and nuclear nitrotyrosine could be decreased with small interfering RNAs to Nox1 and Nox4. Finally, HCV increased the level of transforming growth factor beta 1 (TGFbeta1). TGFbeta1 could elevate Nox4 expression in the presence of infectious HCV, and HCV increased Nox4 at least in part through TGFbeta1. CONCLUSION: HCV induced a persistent elevation of Nox1 and Nox4 and increased nuclear localization of Nox4 in hepatocytes in vitro and in the human liver. Hepatocyte Nox proteins are likely to act as a persistent, endogenous source of ROS during HCV-induced pathogenesis. PMID- 20578129 TI - Down-regulated microRNA-152 induces aberrant DNA methylation in hepatitis B virus related hepatocellular carcinoma by targeting DNA methyltransferase 1. AB - The hepatitis B virus (HBV) X protein has been implicated as a potential trigger of the epigenetic modifications of some genes during hepatocarcinogenesis, but the underlying mechanisms remain unknown. MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in diverse biological functions and in carcinogenesis. In this study, we investigated whether some miRNAs are aberrantly expressed and involved in the regulation of the abnormal DNA methylation status in HBV-related hepatocellular carcinoma (HCC). Our results showed that the expression of microRNA-152 (miR-152) was frequently down regulated in HBV-related HCC tissues in comparison with adjacent noncancerous hepatic tissues and was inversely correlated to DNA methyltransferase 1 (DNMT1) messenger RNA (mRNA) expression in HBV-related HCCs. The forced expression of miR 152 in liver cell lines resulted in a marked reduction of the expression of DNMT1 at both the mRNA and protein levels by directly targeting the 3' untranslated regions of DNMT1. This in turn led to a decrease in global DNA methylation, whereas inhibition of miR-152 caused global DNA hypermethylation and increased the methylation levels of two tumor suppressor genes, glutathione S-transferase pi 1 (GSTP1) and E-cadherin 1 (CDH1). CONCLUSION: Our findings suggest that miR 152 is frequently down-regulated and regulates DNMT1 in HBV-related HCC. These findings support a tumor-suppressive role of miR-152 in the epigenetic aberration of HBV-related HCC and the potential development of miRNA-based targeted approaches for the treatment of HBV-related HCC. PMID- 20578130 TI - Hepatic steatosis in patients coinfected with human immunodeficiency virus/hepatitis C virus: a meta-analysis of the risk factors. AB - Hepatic steatosis (HS) is frequent in patients with hepatitis C virus (HCV) infection, occurring in 40%-80%, associating with metabolic and virus-related factors, namely, genotype 3 and viral load. Human immunodeficiency virus (HIV) infection and antiretroviral treatment seem to be risk factors for HS. Several studies addressed this issue in coinfected patients, with discrepant results. A meta-analysis was performed on the HS risk factors in coinfected patients. Eligible studies were identified through structured keywords including coinfection, HCV, HIV, and steatosis in relevant databases including PubMed. Pooled odds ratios (ORs) and confidence limits (CIs) were obtained with the random-effects model and the DerSimonian-Laird method. Twelve studies, including 1,989 coinfected patients, were selected. Twenty percent were infected with HCV genotype 3. The overall prevalence of HS was 50.8% (23%-72%). Four studies also included 1,540 HCV monoinfected patients, not showing an increased risk for HS in coinfected patients (OR 1.61, 95% CI 0.84-3.10, P = 0.151). In coinfected patients, HS was associated with higher body mass index (OR 1.13, 95% CI 1.07 1.19, P < 0.001), diabetes mellitus (OR 2.32, 95% CI 1.32-4.07, P = 0.003), elevated alanine aminotransferase levels (OR 1.28, 95% CI 1.02-1.61, P = 0.035), necroinflammatory activity (OR 1.72, 95% CI 1.11-2.67, P = 0.016), and fibrosis (OR 1.67, 95% CI 1.20-2.34, P = 0.003). No associations were found between HS and gender, other metabolic factors (dyslipidemia, glucose, metabolic syndrome), HCV related factors (genotype, viral load), or HIV-related factors (viral load, CD4 count, antiretroviral therapy, and class of medication). CONCLUSION: In coinfected patients, HS does not seem to be more frequent than in HCV monoinfected patients and is mostly associated with metabolic factors, such as increased weight, diabetes mellitus, and more severe liver disease. The fact that no associations with HCV factors were found may be due to the small percentage of genotype 3-infected patients. PMID- 20578131 TI - Subtelomeric 6p monosomy and 12q trisomy in a patient with a 46,XX,der(6)t(6;12)(p25.3;q24.31) karyotype: Phenotypic overlap with Mutchinick syndrome. AB - We report on a patient with partial monosomy 6p and partial trisomy 12q identified by fluorescent in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH). She had a complex phenotype characterized by mental retardation (MR), psychomotor developmental delay, speech disorder, hypertelorism, eye anomalies, hearing loss, low-set malformed ears, thin upper lip, heart defect, clinodactyly, pes valgus, and skeletal anomalies. There is phenotypic overlap between our case and Mutchinick syndrome. This is the first report of a combined partial monosomy 6p and partial trisomy 12q due to an unbalanced translocation between subtelomeric regions of these chromosomes. PMID- 20578132 TI - Micellar electrokinetic chromatography for the determination of cortisol in urine samples in view of biomedical studies. AB - An MEKC method used for the determination of cortisol in urine was developed and elaborated. In turn, the measurements of urinary free cortisol provided the diagnostic information for excess adrenal production of cortisol. MEKC realized by the addition of anionic surfactant SDS to the buffer solution was demonstrated to be the appropriate mode for the separation of cortisol and dexamethasone was used as internal standard. A buffer solution composed of 10 mM sodium tetraborate and 50 mM SDS at pH 8.8 was used. The MEKC assay was evaluated by analyzing a series of urine samples containing cortisol in variable concentrations. The proposed method was validated for specificity, linearity, LODs and LOQs, precision and trueness. The LOQ for cortisol equaled 5 ng/mL. The method was selective and reliable for identification and can detect changes of endogenous levels of cortisol in urine under different stress situations. PMID- 20578133 TI - A de novo duplication of Xp11.22-p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome. AB - Only a small number of individuals with duplications within the proximal short arm of the X chromosome have been reported. The majority of patients have duplications encompassing Xp11-p21, or extend more distally into Xp22. We report on a female patient who presented within the first year of life with plagiocephaly, speech delay, and epilepsy. Brain MRI showed a relatively thin cerebral cortex, abnormal periventricular white matter, and abnormal vessels in the left inferior parietal region. Cytogenetic and microsatellite analysis of the patient and her parents showed that she has a de novo duplication of Xp11.22 Xp11.4 on her paternal X chromosome. FISH analysis using fluorescently labeled BACs followed by array analysis including an X tilepath BAC array showed that a 12.3 Mb interval between 40.4 Mb and 52.7 Mb from the Xp telomere (NCBI build 36) was duplicated and excluded the presence of additional rearrangements along the X chromosome. Interestingly, X-inactivation studies in peripheral blood leukocytes showed that the duplicated (paternal) X chromosome was active in the majority of cells, in contrast to other patients with Xp duplications in whom X inactivation is random or skewed toward the normal X. These findings suggest that overexpression of genes from proximal Xp is likely to have contributed to her clinical phenotype. PMID- 20578134 TI - Syndromic mental retardation with thrombocytopenia due to 21q22.11q22.12 deletion: Report of three patients. AB - During the last few years, an increasing number of microdeletion/microduplication syndromes have been delineated. This rapid evolution is mainly due to the availability of microarray technology as a routine diagnostic tool. Microdeletions of the 21q22.11q22.12 region encompassing the RUNX1 gene have been reported in nine patients presenting with syndromic thrombocytopenia and mental retardation. RUNX1 gene is responsible for an autosomal dominant platelet disorder with predisposition to acute myelogenous leukemia. We report on three novel patients with an overlapping "de novo" interstitial deletion involving the band 21q22 characterized by array-CGH. All our patients presented with severe developmental delay, dysmorphic features, behavioral problems, and thrombocytopenia. Comparing the clinical features of our patients with the overlapping ones already reported two potential phenotypes related to 21q22 microdeletion including RUNX1 were highlighted: thrombocytopenia with +/- mild dysmorphic features and syndromic thrombocytopenia with growth and developmental delay. PMID- 20578135 TI - How valid are the rates of Down syndrome internationally? Findings from the International Clearinghouse for Birth Defects Surveillance and Research. AB - Rates of Down syndrome (DS) show considerable international variation, but a systematic assessment of this variation is lacking. The goal of this study was to develop and test a method to assess the validity of DS rates in surveillance programs, as an indicator of quality of ascertainment. The proposed method compares the observed number of cases with DS (livebirths plus elective pregnancy terminations, adjusted for spontaneous fetal losses that would have occurred if the pregnancy had been allowed to continue) in each single year of maternal age, with the expected number of cases based on the best-published data on rates by year of maternal age. To test this method we used data from birth years 2000 to 2005 from 32 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research. We computed the adjusted observed versus expected ratio (aOE) of DS birth prevalence among women 25-44 years old. The aOE ratio was close to unity in 13 programs (the 95% confidence interval included 1), above 1 in 2 programs and below 1 in 18 programs (P < 0.05). These findings suggest that DS rates internationally can be evaluated simply and systematically, and underscores how adjusting for spontaneous fetal loss is crucial and feasible. The aOE ratio can help better interpret and compare the reported rates, measure the degree of under- or over-registration, and promote quality improvement in surveillance programs that will ultimately provide better data for research, service planning, and public health programs. PMID- 20578136 TI - Holoprosencephaly and genitourinary anomalies in fetal methotrexate syndrome. AB - Prenatal exposure to methotrexate (MTX) in the first trimester may lead to fetal death, and surviving children have increased risks for cranial dysostosis, dysmorphic facies, skeletal malformations, limb defects, growth retardation, and, in some cases, developmental delay, a pattern of defects recognized as fetal MTX syndrome (FMS). We report on a male infant who, in addition to severe FMS, showed previously undescribed central nervous system (CNS) and genitourinary anomalies that contributed to the further delineation. The propositus was born to a G2, 20 year-old mother with an irregular menstrual history. The unplanned pregnancy was complicated by oral MTX treatment (5 mg/day) for suspected systemic lupus erythematosus for 14 days at the 5th week post-conception, as dated by the first trimester sonogram. In addition to the typical features of the FMS, our propositus exhibited congenital penile curvature, vesicoureteral reflux, hydronephrosis, and severe CNS anomalies including semilobar holoprosencephaly (HPE). A single previous report of lobar-type HPE in an infant with FMS led us to confirm that the HPE observed in the propositus is a feature attributable to MTX teratogenicity, although the exact mechanisms of the HPE production need to be further elucidated. Also, this case serves to highlight the presence of genitourinary anomalies in patients with FMS, a fact that requires intentional searches in future patients in order to confirm this as being characteristic of the entity. PMID- 20578137 TI - Newborn and carrier screening for spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. The homozygous absence of SMN1 exon 7 has been observed in the majority of patients and is being utilized as a reliable and sensitive SMA diagnostic test. Treatment and prevention of SMA are complementary responses to the challenges presented by SMA. Even though a specific therapy for SMA is not currently available, a newborn screening test may allow the child to be enrolled in a clinical trial before irreversible neuronal loss occurs and enable patients to obtain more proactive treatments. Until an effective treatment is found to cure or arrest the progression of the disease, prevention of new cases through accurate diagnosis and carrier and prenatal diagnosis is of the utmost importance. The goal of population-based SMA carrier screening is to identify couples at risk for having a child with SMA, thus allowing carriers to make informed reproductive choices. During this study we performed two pilot projects addressing the clinical applicability of testing in the newborn period and carrier screening in the general population. We have demonstrated that an effective technology does exist for newborn screening of SMA. We also provide an estimate of the carrier frequency among individuals who accepted carrier screening, and report on patient's knowledge and attitudes toward SMA testing. PMID- 20578138 TI - Controlled trial of ligation plus nadolol versus nadolol alone for the prevention of first variceal bleeding. AB - Both nadolol and ligation have proved to be effective in the prophylaxis of first variceal bleeding. This study was conducted to evaluate the effects and safety of combining nadolol with ligation. Cirrhotic patients with high-risk esophageal varices but without a bleeding history were considered for enrolment. Eligible patients were randomized to receive band ligation plus nadolol (Combined group, 70 patients) or nadolol alone (Nadolol group, 70 patients). In the Combined group multiligators were applied. Patients received regular ligation treatment at an interval of 4 weeks until variceal obliteration. Nadolol was administered at a dose to reduce 25% of the pulse rate in both the Combined group and the Nadolol group. Both groups were comparable in baseline data. In the Combined group 50 patients (71%) achieved variceal obliteration. The mean dose of nadolol was 52 +/ 16 mg in the Combined group and 56 +/- 19 mg in the Nadolol group. During a median follow-up of 26 months, 18 patients (26%) in the Combined group and 13 patients (18%) in the Nadolol group experienced upper gastrointestinal bleeding (P = NS). Esophageal variceal bleeding occurred in 10 patients (14%) in the Combined group and nine patients (13%) in the Nadolol group (P = NS). Adverse events were noted in 48 patients (68%) in the Combined group and 28 patients (40%) in the Nadolol group (P = 0.06). Sixteen patients in each group died. CONCLUSION: The addition of ligation to nadolol may increase adverse events and did not enhance effectiveness in the prophylaxis of first variceal bleeding. PMID- 20578139 TI - Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. AB - Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended but may not be performed. The extent and determinants of HCC surveillance are unknown. We conducted a population-based United States cohort study of patients over 65 years of age to examine use and determinants of prediagnosis surveillance in patients with HCC who were previously diagnosed with cirrhosis. Patients diagnosed with HCC during 1994-2002 were identified from the linked Surveillance, Epidemiology, and End-Results registry-Medicare databases. We identified alpha-fetoprotein (AFP) and ultrasound tests performed for HCC surveillance, and examined factors associated with surveillance. We identified 1,873 HCC patients with a prior diagnosis of cirrhosis. In the 3 years before HCC, 17% received regular surveillance and 38% received inconsistent surveillance. In a subset of 541 patients in whom cirrhosis was recorded for 3 or more years prior to HCC, only 29% received routine surveillance and 33% received inconsistent surveillance. Among all patients who received regular surveillance, approximately 52% received both AFP and ultrasound, 46% received AFP only, and 2% received ultrasound only. Patients receiving regular surveillance were more likely to have lived in urban areas and had higher incomes than those who did not receive surveillance. Before diagnosis, approximately 48% of patients were seen by a gastroenterologist/hepatologist or by a physician with an academic affiliation; they were approximately 4.5-fold and 2.8-fold, respectively, more likely to receive regular surveillance than those seen by a primary care physician only. Geographic variation in surveillance was observed and explained by patient and physician factors. CONCLUSION: Less than 20% of patients with cirrhosis who developed HCC received regular surveillance. Gastroenterologists/hepatologists or physicians with an academic affiliation are more likely to perform surveillance. PMID- 20578140 TI - Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage. AB - One of the serious sequelae of chronic hepatitis B virus (HBV) infection is hepatocellular carcinoma (HCC). Among all the proteins encoded by the HBV genome, hepatitis B virus X protein (HBx) is highly associated with the development of HCC. Although Notch1 signaling has been found to exert a tumor-suppressive function during HCC development, the mechanism of interaction between HBx expression and Notch1 signaling needs to be explored. In this study, we report that HBx expression in hepatic and hepatoma cells resulted in decreased endogenous protein levels of Notch1 intracellular domain (ICN1) and messenger RNA levels of its downstream target genes. These effects were due to a reduction of Notch1 cleavage by HBx through the suppression of presenilin1 (Psen1) transcription rather than inhibition of Notch1 transcription or its ligands' expression. Through transient HBx expression, decreased ICN1 resulted in enhanced cell proliferation, induced G1-S cell cycle progression, and blunted cellular senescence in vitro. Furthermore, the effect of blunted senescence-like growth arrest by stable HBx expression through suppression of ICN1 was shown in a nude mouse xenograft transplantation model. The correlation of inhibited Psen1 dependent Notch1 signaling and blunted senescence-like growth arrest was also observed in HBV-associated HCC patient tumor samples. CONCLUSION: Our results reveal a novel function of HBx in blunting senescence-like growth arrest by decreasing Notch1 signaling, which could be a putative molecular mechanism mediating HBV-associated hepatocarcinogenesis. PMID- 20578141 TI - Does levator ani injury affect cystocele type? AB - OBJECTIVE: To determine the prevalence of levator ani injury in patients with different types of cystocele, as defined by translabial ultrasound, in order to shed light on potential pathophysiological mechanisms. METHODS: The datasets of 222 women who had undergone a physical examination, urodynamic testing and four dimensional (4D) pelvic floor ultrasound were evaluated offline for prolapse, levator ani hiatal dimensions and levator ani trauma using tomographic ultrasound imaging (TUI), blinded against all clinical and urodynamic data. Cystoceles reaching below the symphysis pubis on ultrasound examination were classified based on bladder neck position, retrovesical angle (RVA) and urethral rotation as Green II (cystourethrocele) or Green III (cystocele with intact RVA). RESULTS: Of 102 women who had a cystocele reaching below the symphysis pubis, 63 were classified as a Green type II cystocele and 39 as a Green type III cystocele. Women with Green type III cystoceles were older (59.4 vs. 48.7 years, P < 0.001), and had more severe prolapse (71 vs. 43%, P = 0.004) and objective voiding dysfunction (39 vs. 18%, P = 0.018). Women with Green III cystoceles also had larger hiatal dimensions and were more often diagnosed with an avulsion of the levator ani muscle (69 vs. 35%, P = 0.001). CONCLUSION: A cystocele with an intact RVA is more likely to be associated with avulsion injury of the levator ani muscle and thus more likely to be caused by birth-related trauma. This contradicts the commonly held belief that such cystoceles are caused by central rather than by lateral fascial defects. PMID- 20578142 TI - Aquaporin-1 facilitates angiogenic invasion in the pathological neovasculature that accompanies cirrhosis. AB - Increasing evidence suggests that hepatic fibrosis and pathological angiogenesis are interdependent processes that occur in parallel. Endothelial cell invasion is requisite for angiogenesis, and thus studies of the mechanisms governing liver endothelial cell (LEC) invasion during cirrhosis are of great importance. Emerging research implicates amoeboid-type motility and membrane blebbing as features that may facilitate invasion through matrix-rich microenvironments. Aquaporins (AQPs) are integral membrane water channels, recognized for their importance in epithelial secretion and absorption. However, recent studies also suggest links between water transport and cell motility or invasion. Therefore, the purpose of this study was to test the hypothesis that AQP-1 is involved in amoeboid motility and angiogenic invasion during cirrhosis. AQP-1 expression and localization was examined in normal and cirrhotic liver tissues derived from human and mouse. AQP-1 levels were modulated in LEC using retroviral overexpression or small interfering RNA (siRNA) knockdown and functional effects on invasion, membrane blebbing dynamics, and osmotic water permeability were assayed. Results demonstrate that AQP-1 is up-regulated in the small, angiogenic, neovasculature within the fibrotic septa of cirrhotic liver. AQP-1 overexpression promotes fibroblast growth factor (FGF)-induced dynamic membrane blebbing in LEC, which is sufficient to augment invasion through extracellular matrix. Additionally, AQP-1 localizes to plasma membrane blebs, where it increases osmotic water permeability and locally facilitates the rapid, trans-membrane flux of water. CONCLUSION: AQP-1 enhances osmotic water permeability and FGF-induced dynamic membrane blebbing in LEC and thereby drives invasion and pathological angiogenesis during cirrhosis. PMID- 20578143 TI - Detection of the imbalance of procoagulant versus anticoagulant factors in cirrhosis by a simple laboratory method. AB - Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin generation assay performed in the presence/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%]; P < 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%]; P = 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728, P < 0.001) or factor VIII (rho = -0.517, P < 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = -0.580, P < 0.001). CONCLUSION: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. PMID- 20578144 TI - Macroautophagy and chaperone-mediated autophagy are required for hepatocyte resistance to oxidant stress. AB - The function of the lysosomal degradative pathway of autophagy in cellular injury is unclear, because findings in nonhepatic cells have implicated autophagy as both a mediator of cell death and as a survival response. Autophagic function is impaired in steatotic and aged hepatocytes, suggesting that in these settings hepatocellular injury may be altered by the decrease in autophagy. To delineate the specific function of autophagy in the hepatocyte injury response, the effects of menadione-induced oxidative stress were examined in the RALA255-10G rat hepatocyte line when macroautophagy was inhibited by a short hairpin RNA (shRNA) mediated knockdown of the autophagy gene atg5. Loss of macroautophagy sensitized cells to apoptotic and necrotic death from normally nontoxic concentrations of menadione. Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death. Death occurred from activation of the mitochondrial death pathway with cellular adenosine triphosphate (ATP) depletion, mitochondrial cytochrome c release, and caspase activation. Sensitization to death from menadione occurred despite up-regulation of other forms of autophagy in compensation for the loss of macroautophagy. Chaperone-mediated autophagy (CMA) also mediated resistance to menadione. CMA inhibition sensitized cells to death from menadione through a mechanism different from that of a loss of macroautophagy, because death occurred in the absence of JNK/c-Jun overactivation or ATP depletion. CONCLUSION: Hepatocyte resistance to injury from menadione-induced oxidative stress is mediated by distinct functions of both macroautophagy and CMA, indicating that impaired function of either form of autophagy may promote oxidant-induced liver injury. PMID- 20578145 TI - Activation of Rac1 promotes hedgehog-mediated acquisition of the myofibroblastic phenotype in rat and human hepatic stellate cells. AB - Hepatic accumulation of myofibroblastic hepatic stellate cells (MF-HSCs) is pivotal in the pathogenesis of cirrhosis. Two events are necessary for MF-HSCs to accumulate in damaged livers: transition of resident, quiescent hepatic stellate cells (Q-HSCs) to MF-HSCs and expansion of MF-HSC numbers through increased proliferation and/or reduced apoptosis. In this study, we identified two novel mediators of MF-HSC accumulation: Ras-related C3 botulinum toxin substrate 1 (Rac1) and Hedgehog (Hh). It is unclear whether Rac1 and Hh interact to regulate the accumulation of MF-HSCs. We evaluated the hypothesis that Rac1 promotes activation of the Hh pathway, thereby stimulating signals that promote transition of Q-HSCs into MF-HSCs and enhance the viability of MF-HSCs. Using both in vitro and in vivo model systems, Rac1 activity was manipulated through adenoviral vector-mediated delivery of constitutively active or dominant-negative rac1. Rac1 transgenic mice with targeted myofibroblast expression of a mutated human rac1 transgene that produces constitutively active Rac1 were also examined. Results in all models demonstrated that activating Rac1 in HSC enhanced Hh signaling, promoted acquisition/maintenance of the MF-HSC phenotype, increased MF-HSC viability, and exacerbated fibrogenesis. Conversely, inhibiting Rac1 with dominant-negative rac1 reversed these effects in all systems examined. Pharmacologic manipulation of Hh signaling demonstrated that profibrogenic actions of Rac1 were mediated by its ability to activate Hh pathway-dependent mechanisms that stimulated myofibroblastic transition of HSCs and enhanced MF-HSC viability. CONCLUSION: These findings demonstrate that interactions between Rac1 and the Hh pathway control the size of MF-HSC populations and have important implications for the pathogenesis of cirrhosis. PMID- 20578147 TI - Ferritin and liver allocation? Impact on mortality not only on the waiting list but also after orthotopic liver transplantation should be considered. PMID- 20578150 TI - Bid agonist regulates murine hepatocyte proliferation by controlling endoplasmic reticulum calcium homeostasis. AB - BH3-interacting domain death agonist (Bid), a BH3-only B cell lymphoma 2 family molecule, is generally known for its importance in activating the mitochondrial apoptosis pathway after death receptor engagement, particularly in hepatocytes. However, Bid also promotes hepatocyte proliferation during liver regeneration and carcinogenesis. This study was designed to examine the hypothesis that Bid regulates endoplasmic reticulum calcium concentration ([Ca(2+)](ER)) homeostasis to affect hepatocyte proliferation. We found that serum-stimulated hepatocyte proliferation was dependent on calcium, and the depletion of calcium with thapsigargin or ethylene glycol tetraacetic acid (EGTA) inhibited the proliferation. Subcellular fractionation showed that a portion of Bid was inserted into the endoplasmic reticulum (ER)-enriched membranes, and single-cell calcium imaging indicated that Bid was important for maintaining the [Ca(2+)](ER) level. Bid-deficient hepatocytes manifested delayed and reduced serum-stimulated proliferation, which was corrected by ionomycin or reconstitution of Bid, particularly an ER-targeted Bid. Finally, B cell lymphoma 2-associated X protein (Bax) could also be found in the ER-enriched membranes, and Bax deficiency caused the same proliferation defect. However, Bid/Bax double deletion in hepatocytes did not further augment the defect, which suggested that Bid and Bax worked by the same regulatory mechanism in [Ca(2+)](ER) control. CONCLUSION: Bid regulates hepatocyte proliferation by positively affecting [Ca(2+)](ER) homeostasis, and this could be important for liver regeneration and carcinogenesis. PMID- 20578151 TI - American Association for the Study of Liver Diseases endpoints conference: design and endpoints for clinical trials in primary biliary cirrhosis. PMID- 20578149 TI - Regulation of multidrug resistance-associated protein 2 by calcium signaling in mouse liver. AB - Multidrug resistance associated protein 2 (Mrp2) is a canalicular transporter responsible for organic anion secretion into bile. Mrp2 activity is regulated by insertion into the plasma membrane; however, the factors that control this are not understood. Calcium (Ca(2+)) signaling regulates exocytosis of vesicles in most cell types, and the type II inositol 1,4,5-triphosphate receptor (InsP(3)R2) regulates Ca(2+) release in the canalicular region of hepatocytes. However, the role of InsP(3)R2 and of Ca(2+) signals in canalicular insertion and function of Mrp2 is not known. The aim of this study was to determine the role of InsP(3)R2 mediated Ca(2+) signals in targeting Mrp2 to the canalicular membrane. Livers, isolated hepatocytes, and hepatocytes in collagen sandwich culture from wild-type (WT) and InsP(3)R2 knockout (KO) mice were used for western blots, confocal immunofluorescence, and time-lapse imaging of Ca(2+) signals and of secretion of a fluorescent organic anion. Plasma membrane insertion of green fluorescent protein (GFP)-Mrp2 expressed in HepG2 cells was monitored by total internal reflection microscopy. InsP(3)R2 was concentrated in the canalicular region of WT mice but absent in InsP(3)R2 KO livers, whereas expression and localization of InsP(3)R1 was preserved, and InsP(3)R3 was absent from both WT and KO livers. Ca(2+) signals induced by either adenosine triphosphate (ATP) or vasopressin were impaired in hepatocytes lacking InsP(3)R2. Canalicular secretion of the organic anion 5-chloromethylfluorescein diacetate (CMFDA) was reduced in KO hepatocytes, as well as in WT hepatocytes treated with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acid (BAPTA). Moreover, the choleretic effect of tauroursodeoxycholic acid (TUDCA) was impaired in InsP(3)R2 KO mice. Finally, ATP increased GFP-Mrp2 fluorescence in the plasma membrane of HepG2 cells, and this also was reduced by BAPTA. CONCLUSION: InsP(3)R2-mediated Ca(2+) signals enhance organic anion secretion into bile by targeting Mrp2 to the canalicular membrane. PMID- 20578153 TI - Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. AB - The rapid emergence of nonalcoholic fatty liver disease (NAFLD) as a cause of both liver-related morbidity and mortality and cardiometabolic risk has led to the search for effective lifestyle strategies to reduce liver fat. Lifestyle intervention comprising dietary restriction in conjunction with increased physical activity has shown clear hepatic benefits when weight loss approximating 3%-10% of body weight is achieved. Yet, the poor sustainability of weight loss challenges the current therapeutic focus on body weight and highlights the need for alternative strategies for NAFLD management. Epidemiologic data show an independent relationship between liver fat, physical activity, and fitness, and a growing body of longitudinal research demonstrates that increased physical activity participation per se significantly reduces hepatic steatosis and serum aminotransferases in individuals with NAFLD, independent of weight loss. Mechanistic insights to explain this interaction are outlined, and recommendations for the implementation of lifestyle intervention involving physical activity are discussed. In light of the often poor sustainability of weight loss strategies, and the viability of physical activity therapy, clinicians should assess physical fitness and physical activity habits, educate patients on the benefits of fitness outside of weight loss, and focus on behavior change which promotes physical activity adoption. PMID- 20578152 TI - Sorafenib: where do we go from here? AB - The approval of sorafenib as the first effective drug for the treatment of hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis has led to the development of several novel targeted treatments. HCC is treated in a uniquely multidisciplinary way requiring surgeons, hepatologists, interventional radiologists, and oncologists. This review describes the molecular pathogenesis of HCC, explores current and future treatments based on these pathways, and describes how these new therapies may augment existing approaches to HCC treatment. PMID- 20578154 TI - Another cause of autoimmune hepatitis. PMID- 20578155 TI - Cigarette smoking is not associated with specific histological features or severity of nonalcoholic fatty liver disease. PMID- 20578156 TI - Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. AB - Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin-positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFkappaB) activation and dose dependent proliferation, which was diminished after targeting of the p50 NFkappaB subunit by RNA interference. CONCLUSION: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFkappaB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. PMID- 20578157 TI - Mitochondrial superoxide dismutase and glutathione peroxidase in idiosyncratic drug-induced liver injury. AB - Drug-induced liver injury (DILI) susceptibility has a potential genetic basis. We have evaluated possible associations between the risk of developing DILI and common genetic variants of the manganese superoxide dismutase (SOD2 Val16Ala) and glutathione peroxidase (GPX1 Pro200Leu) genes, which are involved in mitochondrial oxidative stress management. Genomic DNA from 185 DILI patients assessed by the Council for International Organizations of Medical Science scale and 270 sex- and age-matched controls were analyzed. The SOD2 and GPX1 genotyping was performed using polymerase chain reaction restriction fragment length polymorphism and TaqMan probed quantitative polymerase chain reaction, respectively. The statistical power to detect the effect of variant alleles with the observed odds ratio (OR) was 98.2% and 99.7% for bilateral association of SOD2 and GPX1, respectively. The SOD2 Ala/Ala genotype was associated with cholestatic/mixed damage (OR = 2.3; 95% confidence interval [CI] = 1.4-3.8; corrected P [Pc] = 0.0058), whereas the GPX1 Leu/Leu genotype was associated with cholestatic injury (OR = 5.1; 95%CI = 1.6-16.0; Pc = 0.0112). The presence of two or more combined risk alleles (SOD2 Ala and GPX1 Leu) was more frequent in DILI patients (OR = 2.1; 95%CI = 1.4-3.0; Pc = 0.0006). Patients with cholestatic/mixed injury induced by mitochondria hazardous drugs were more prone to have the SOD2 Ala/Ala genotype (OR = 3.6; 95%CI = 1.4-9.3; Pc = 0.02). This genotype was also more frequent in cholestatic/mixed DILI induced by pharmaceuticals producing quinone-like or epoxide metabolites (OR = 3.0; 95%CI = 1.7-5.5; Pc = 0.0008) and S-oxides, diazines, nitroanion radicals, or iminium ions (OR = 16.0; 95%CI = 1.8-146.1; Pc = 0.009). CONCLUSION: Patients homozygous for the SOD2 Ala allele and the GPX1 Leu allele are at higher risk of developing cholestatic DILI. SOD2 Ala homozygotes may be more prone to suffer DILI from drugs that are mitochondria hazardous or produce reactive intermediates. PMID- 20578158 TI - Liver sinusoidal endothelium: a microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein-1. AB - Liver sinusoidal endothelium (LSEC) is a prime example of organ-specific microvascular differentiation and functions. Disease-associated capillarization of LSEC in vivo and dedifferentiation of LSEC in vitro indicate the importance of the hepatic microenvironment. To identify the LSEC-specific molecular differentiation program in the rat we used a two-sided gene expression profiling approach comparing LSEC freshly isolated ex vivo with both lung microvascular endothelial cells (LMEC) and with LSEC cultured for 42 hours. The LSEC signature consisted of 48 genes both down-regulated in LMEC and in LSEC upon culture (fold change >7 in at least one comparison); quantitative reverse-transcription polymerase chain reaction confirmation of these genes included numerous family members and signaling pathway-associated molecules. The LSEC differentiation program comprised distinct sets of growth (Wnt2, Fzd4, 5, 9, Wls, vascular endothelial growth factors [VEGFR] 1, 2, 3, Nrp2) and transcription factors (Gata4, Lmo3, Tcfec, Maf) as well as endocytosis-related (Stabilin-1/2, Lyve1, and Ehd3) and cytoskeleton-associated molecules (Rnd3/RhoE). Specific gene induction in cultured LSEC versus freshly isolated LSEC as well as LMEC (Esm-1, Aatf) and up-regulation of gene expression to LMEC levels (CXCR4, Apelin) confirmed true transdifferentiation of LSEC in vitro. In addition, our analysis identified a novel 26-kDa single-pass transmembrane protein, liver endothelial differentiation-associated protein (Leda)-1, that was selectively expressed in all liver endothelial cells and preferentially localized to the abluminal cell surface. Upon forced overexpression in MDCK cells, Leda-1 was sorted basolaterally to E-cadherin-positive adherens junctions, suggesting functional involvement in cell adhesion and polarity. CONCLUSION: Comparative microvascular analysis in rat identified a hepatic microenvironment-dependent LSEC-specific differentiation program including the novel junctional molecule Leda-1. PMID- 20578159 TI - Routine hepatitis B virus DNA testing in patients with human immunodeficiency virus. PMID- 20578160 TI - Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis. AB - Carbamoyl-phosphate synthetase I (CPS1) deficiency (CPS1D), a recessively inherited urea cycle error due to CPS1 gene mutations, causes life-threatening hyperammonemia. The disease-causing potential of missense mutations in CPS1 deficiency can be ascertained with the recombinant CPS1 expression and purification system reported here, which uses baculovirus and insect cells. We study with this system the effects of nine clinical mutations and one polymorphism on CPS1 solubility, stability, activity, and kinetic parameters for NAG. Five of the mutations (p.T471N, p.Q678P, p.P774L, p.R1453Q, and p.R1453W) are first reported here, in three severe CPS1D patients. p.P774L, p.R1453Q, and p.R1453W inactivate CPS1, p.T471N and p.Y1491H greatly decrease the apparent affinity for NAG, p.Q678P hampers correct enzyme folding, and p.S123F, p.H337R, and p.P1411L modestly decrease activity. p.G1376S is confirmed a trivial polymorphism. The effects of the C-terminal domain mutations are rationalized in the light of this domain crystal structure, including the NAG site structure [Pekkala et al. Biochem J 424:211-220]. The agreement of clinical observations and in vitro findings, and the possibility to identify CPS1D patients who might benefit from specific treatment with NAG analogues because they exhibit reduced affinity for NAG highlight the value of this novel CPS1 expression/purification system. PMID- 20578161 TI - Use of Stingray re-entry system in treatment of complex tibial artery occlusive disease. AB - One of the mechanisms of technical failure in the treatment of tibial artery occlusive disease includes an inability to re-enter the true lumen of the tibial vessel distal to the occlusion following tracking of the interventional wire into the subintimal space. We report the first case using a coronary 0.014" re-entry system (Stingray Chronic Total Occlusions Re-entry System, BridgePoint Medical) in the treatment of a complex tibial artery occlusion where the antegrade approach initially failed due to this mechanism. The re-entry system allowed completion of antegrade recanalization of the occlusion and represents an important addition to the interventional armamentarium for the treatment of complex tibial artery disease. PMID- 20578162 TI - Effects of aspiration thrombectomy on necrosis size and ejection fraction after transradial percutaneous coronary intervention in acute ST-elevation myocardial infarction. AB - BACKGROUND: The use of routine aspiration thrombectomy in primary percutaneous coronary intervention (PCI) remains controversial. METHODS: Patients in the EArly Discharge after Transradial Stenting of CoronarY Arteries in Acute Myocardial Infarction (n = 105) study were treated with aspirin, clopidogrel, and abciximab within 6 hr of symptoms onset. Operators were allowed to use 6 Fr Export aspiration catheter at their discretion. In this observational analysis, we compared acute and late results in patients treated with and without thrombectomy using cardiac biomarkers, angiographic, cardiovascular magnetic resonance (CMR), and clinical parameters. RESULTS: Patients in the thrombectomy group (n = 44) had longer symptoms to balloon time (196 +/- 86 min vs. 164 +/- 62, P = 0.039) and higher incidence of preprocedural TIMI flow grade 0 or 1 (84% vs. 64%, P = 0.028). Following PCI, both groups had similar incidence of TIMI flow grade 3 (93 vs. 92%, P = 0.73) and myocardial blush grade 2 or 3 (80 vs. 77%, P = 0.86), respectively. Patients in thrombectomy group had significantly higher post-PCI maximum values of creatine kinase-MB (P = 0.0007) and troponin T (P = 0.0010). Accordingly, post-PCI myocardial necrosis by CMR was higher (P = 0.0030) in patients in the thrombectomy group. At 6-month follow-up, necrosis size remained higher (20.7% +/- 13.3% vs. 13.5% +/- 11.1%, P = 0.012) in the thrombectomy group. Ejection fraction at 6 months was 65% +/- 9% in patients in thrombectomy group compared to 70% +/- 11% in patients without (P = 0.070). Results were not affected by initial TIMI flow or symptoms to balloon time. Clinical events remained comparable in both groups at 12 months follow-up. CONCLUSION: In patients with ST-segment elevation myocardial infarction presenting within 6 hr of symptoms and undergoing primary angioplasty with maximal antiplatelet therapy, acute and late results did not suggest significant benefit for additional aspiration thrombectomy, irrespective of initial TIMI flow or total ischemic time. PMID- 20578163 TI - EuroSCORE is a good global predictor of long-term outcomes in high-risk but not in low-risk patients after unprotected left main angioplasty. AB - BACKGROUND: Percutaneous coronary intervention is increasingly emerging as a valuable alternative to surgery for the treatment of patients with unprotected left main coronary artery (ULMCA) disease. In this study, we aimed to assess the ability of the EuroSCORE risk stratification model to predict long-term major adverse cardiac events after unprotected left main angioplasty according to the individual level of risk. METHODS: Two hundred forty-six consecutive patients who underwent ULMCA in a single high volume center over a 5-year period were included. Major adverse cardiac events were defined as a combined end point of cardiac death, nonfatal myocardial infarction, or target lesion revascularization. RESULTS: Areas under the receiver-operating characteristic curve of EuroSCORE in the entire cohort were 0.687 (P = 0.005; 95% CI: 0.575 0.846) and 0.589 (P = 0.038; 95% CI: 0.511-0.673) respectively for cardiac death and major adverse cardiac events (MACE). One hundred twenty-four patients had a EuroSCORE value > 6 and constituted the high surgical risk (HSR) group. Actuarial 4-year survivals free from cardiac death and free from MACE were significantly lower in this group respectively at 84% versus 93% (log rank P = 0.02) and 50% versus 74% (log rank P = 0.004). EuroSCORE was the only independent predictor of long-term cardiac mortality by the Cox analysis (HR = 3.95, P = 0.027, 95% CI: 1.16-13.39). It had a good discriminatory power for predicting both cardiac death and MACE with AUC respectively at was 0.705 (P = 0.01, 95% CI: 0.55-0.86) and 0.65 (P = 0.013, 95% CI: 0.54-0.78) in the HSR cohort but not in the lower risk (EuroSCORE <= 6) cohort. CONCLUSION: EuroSCORE is a good predictor not only of cardiac death but also of MACE after ULMCA angioplasty; however, the discriminatory ability of EuroSCORE appears to be limited to patients with high surgical risk as defined by EuroSCORE values > 6. PMID- 20578164 TI - Bifurcation lesions: Functional assessment by fractional flow reserve vs. anatomical assessment using conventional and dedicated bifurcation quantitative coronary angiogram. AB - BACKGROUND: The purpose of this study was to compare the performance of both conventional quantitative coronary angiography (QCA) and the dedicated three branch QCA model for bifurcations in the prediction of a functionally significant lesion according to fractional flow reserve (FFR) in patients with bifurcation lesions. METHODS: Twenty patients with bifurcation lesions underwent coronary angiography together with a functional evaluation of both the main branch and side-branch using FFR. QCA was performed off-line with both conventional QCA software (CAASII, Pie Medical Imaging, Maastricht, The Netherlands) and three branch QCA software (CAAS5, Pie Medical Imaging, Maastricht, The Netherlands). A stenosis was considered hemodynamically significant when the FFR value was <= 0.80 and anatomically significant when the diameter stenosis was >50%. The QCA and FFR data were correlated by means of the Pearson correlation. RESULTS: Eighteen bifurcation lesions were suitable for the QCA analysis. In the main vessel, a significant inverse correlation with FFR was seen with both conventional QCA (Pearson r = 0.52 for the MV, P = 0.02), and the three branch QCA model (Pearson r = 0.67 for the MV, P = 0.002). Conversely, in the side branch, the correlation between QCA and FFR was only significant with the three branch QCA model (Pearson r = 0.57, P = 0.02 for the SB). CONCLUSIONS: In bifurcation lesions the correlation between the anatomic severity of a coronary stenosis and its functional significance appears to be somewhat higher when QCA is performed using the three branch model. This is most notable for side-branch stenoses which can be overestimated when using conventional QCA. PMID- 20578165 TI - Awareness of anatomical variations for infrapopliteral intervention. AB - With the tremendous advancement and accumulated expertise of endovascular techniques, infrapopliteal intervention is emerging as an alternative therapeutic option to distal bypass surgery for limb salvage in the setting of critical limb ischemia (CLI). However, though much attention has been given to infrapopliteal intervention, the importance of identifying preprocedural infrapopliteal variants remains underappreciated. Becoming more aware of these anatomical variants will translate to increased clinical effectiveness for the patient with infrapopliteal artery disease. Therefore, this review will highlight the fundamental aspects of infrapopliteal variant anatomy for the catheter-based treatment of CLI patients with symptomatic infrapopliteal artery disease. PMID- 20578166 TI - Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention. AB - OBJECTIVES: The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. METHODS: Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitie-Salpetriere registry of ischemic coronary syndromes (e-PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity-weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. RESULTS: Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti-Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12-0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16 0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12-0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17-0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). CONCLUSIONS: In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. (c) 2010 Wiley-Liss, Inc. PMID- 20578168 TI - Retrograde transcatheter closure of ventricular septal defects in children using the Amplatzer Duct Occluder II. AB - OBJECTIVES: To describe the technique and results of transcatheter closure of ventricular septal defects (VSDs) by a modified retrograde transarterial approach using the new Amplatzer Duct Occluder II (ADO II). BACKGROUND: Transcatheter device closure of ventricular septal defects (VSDs) by antegrade method is well established, but a challenging procedure. We describe a retrograde technique that obviates the need for arteriovenous looping. MATERIAL AND METHODS: This is a prospective study from a single center. Between April 2009 and February 2010 13 children were identified for closure of various types of perimembranous and muscular VSDs using the ADO II device. All had met the criteria for surgical closure. Following left ventricular angiogram two were excluded as technically nonfeasible. The median age was 48 months (range 15-78). The median weight was 14 kg (range 7.5-20). The device was successfully deployed in the 11 selected children by the method described. The follow-up evaluation included chest roentgenogram, ECG, and echocardiogram on day 1, at 6 weeks, at 3, 6, and 12 months. RESULTS: The immediate and follow up complete closure rates were 73 and 82%, respectively. The median fluoroscopic time was 14 min (range 8.2-45). There were no procedure related complications. All patients were doing well at median follow up of 10 months; none showing any conduction abnormality. CONCLUSION: Transcatheter retrograde device closure of selected cases of Ventricular Septal Defects using the Amplatzer Duct Occluder II is simple and appears safe in the short term and can be completed within a short fluoroscopic time. PMID- 20578167 TI - A naturally occurring isoform inhibits parathyroid hormone receptor trafficking and signaling. AB - Parathyroid hormone (PTH) regulates calcium homeostasis and bone remodeling through its cognitive receptor (PTHR). We describe here a PTHR isoform harboring an in-frame 42-bp deletion of exon 14 (Deltae14-PTHR) that encodes transmembrane domain 7. Deltae14-PTHR was detected in human kidney and buccal epithelial cells. We characterized its topology, cellular localization, and signaling, as well as its interactions with PTHR. The C-terminus of the Deltae14-PTHR is extracellular, and cell surface expression is strikingly reduced compared with the PTHR. Deltae14-PTHR displayed impaired trafficking and accumulated in endoplasmic reticulum. Signaling and activation of cAMP and ERK by Deltae14-PTHR was decreased significantly compared with PTHR. Deltae14-PTHR acts as a functional dominant-negative by suppressing the action of PTHR. Cells cotransfected with both receptors exhibit markedly reduced PTHR cell membrane expression, colocalization with Deltae14-PTHR in endoplasmic reticulum, and diminished cAMP activation and ERK phosphorylation in response to challenge with PTH. Deltae14 PTHR forms heterodimers with PTHR, which may account for cytoplasmic retention of PTHR in the presence of Deltae14-PTHR. Analysis of the PTHR heteronuclear RNA suggests that base-pair complementarity in introns surrounding exon 14 causes exon skipping and accounts for generation of the Deltae14-PTHR isoform. Thus Deltae14-PTHR is a poorly functional receptor that acts as a dominant-negative of PTHR trafficking and signaling and may contribute to PTH resistance. PMID- 20578169 TI - Is the human left middle longitudinal fascicle essential for language? A brain electrostimulation study. AB - Human brain pathways required for language processing are poorly known. A new white matter tract in humans, the middle longitudinal fascicle, has recently been anatomically determined by diffusion tensor imaging and suggested to be essential for language. Our aim is to determine the importance of the middle longitudinal fascicle for language processing. This study is based on 8 patients with glioma resection at least involving the superior temporal gyrus of the left dominant hemisphere. Language is systematically examined pre- and postoperatively at 3 months. Intraoperative electrostimulation is used to map cortical and subcortical structures as functional boundaries of the glioma resection, including those essential for language processing. The resections are extensive (on average 62 ml, ranging from 21 to 111 ml) and include a large part of the middle longitudinal fascicle in all patients. Intraoperatively, no interference with picture naming is observed by electrostimulation of the middle longitudinal fascicle, while in all patients the inferior fronto-occipital fascicle is identified by eliciting semantic paraphasia as functional boundary. Postoperatively, no new permanent language deficits are detected by systematic language examination. Therefore, we suggest that the middle longitudinal fascicle may participate but is not essential for language processing. PMID- 20578171 TI - The prognosis of colon cancer is dependent on accurate staging. PMID- 20578170 TI - The vomeronasal organ is not involved in the perception of endogenous odors. AB - Chemosensory-based communication is a vital signaling tool in most species, and evidence has recently emerged in support of the notion that humans also use social chemosignals (so-called pheromones) to communicate. An ongoing controversy does exist, however, concerning the receptor organ through which these chemicals are processed. There is a widespread belief that the vomeronasal organ (VNO) is responsible for processing social chemosignals in humans. Here we demonstrate that functional occlusion of the VNO does not change the percept of, sensitivity toward, or functional neuronal processing of a putative human pheromone. Perithreshold and suprathreshold perception of the endogenous chemical androstadienone (AND) were compared, as were positron emission tomography brain activations evoked by AND when the VNO was either occluded or left open. In addition, we compared sensitivity to AND in subjects with an identifiable VNO to those in whom no VNO could be detected. Thus we could examine the effects of the VNO at several different levels of processing. Occlusion or absence of the VNO did not affect either the perceptual measurements or the functional processing of the putative human pheromone, AND. These results provide strong evidence that the human VNO has no obvious function. Pheromonal communication in humans may be conveyed via the main olfactory system. PMID- 20578172 TI - Meeting the 12 lymph node (LN) benchmark in colon cancer. AB - BACKGROUND: Examining >or=12 LN in colon cancer has been suggested as a quality metric. The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample. METHODS: Patients with stage I-III disease resected at NCCN centers were identified from a prospective database (n = 718) and were compared to 12,845 stage I-III patients diagnosed in a SEER region. Age, gender, location, stage, number of positive nodes were compared for NCCN and SEER data in regards to number of nodes evaluated. Multivariate logistic regression models were developed to identify factors associated with evaluating 12 LNs. RESULTS: 92% of NCCN and 58% of SEER patients had >or=12 LN evaluated. For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided tumors, stage I disease and BMI >30. CONCLUSIONS: >or=12 LN are almost always evaluated in NCCN patients. In contrast, this target is achieved in 58% of SEER patients. With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control. PMID- 20578174 TI - Application of whole-brain CBV-weighted fMRI to a cognitive stimulation paradigm: robust activation detection in a stroop task experiment using 3D GRASE VASO. AB - Brain activation studies generally utilize blood oxygenation level dependent (BOLD) contrast, most commonly measured using the gradient-echo echo-planar imaging (EPI) technique. BOLD contrast arises from regional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the local metabolic rate of oxygen consumption. An alternative to BOLD is the detection of activation through direct measurement of these parameters. A noninvasive approach to measure activation-related CBV changes is the vascular space occupancy (VASO) method, which exploits blood as an endogenous contrast agent by selectively nulling the magnetization of the water spins in the blood. Using a recently developed multislice variant of VASO that enables single-shot whole-brain coverage by virtue of a three-dimensional GRASE readout, we here present the first application of VASO to an fMRI study with a whole-brain cognitive task. Within acceptable measurement times (~12 minutes), brain activation during a Stroop color-word matching task could be detected reliably both on the group (N = 12) and single subject level, as evident from a qualitative comparison with separately acquired BOLD data and literature reports. PMID- 20578175 TI - Thymidylate synthase expression in high-grade neuroendocrine and non-small cell lung cancer histotypes--is it ready for primetime? PMID- 20578173 TI - Correlations of striatal dopamine synthesis with default network deactivations during working memory in younger adults. AB - Age-related deficits have been demonstrated in working memory performance and in the dopamine system thought to support it. We performed positron emission tomography (PET) scans on 12 younger (mean 22.7 years) and 19 older (mean 65.8 years) adults using the radiotracer 6-[(18)F]-fluoro-L-m-tyrosine (FMT), which measures dopamine synthesis capacity. Subjects also underwent functional magnetic resonance imaging (fMRI) while performing a delayed recognition working memory task. We evaluated age-related fMRI activity differences and examined how they related to FMT signal variations in dorsal caudate within each age group. In posterior cingulate cortex and precuneus (PCC/Pc), older adults showed diminished fMRI deactivations during memory recognition compared with younger adults. Greater task-induced deactivation (in younger adults only) was associated both with higher FMT signal and with worse memory performance. Our results suggest that dopamine synthesis helps modulate default network activity in younger adults and that alterations to the dopamine system may contribute to age-related changes in working memory function. PMID- 20578176 TI - Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer. AB - BACKGROUND: Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)-17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line. METHODS: IL-17 expression was investigated in 79 NSCLC tumor tissues by immunohistochemistry. Growth rate, IL-17 mRNA, and secreting protein levels were also examined in HPV 16/18 E6-transfected H1299 human NSCLC cells. RESULTS: Immunohistochemical data showed that 48.1% of lung tumors had IL-17 staining, which was significantly associated with patients' sex (P = .03), HPV infection (P = .002), and tumor stage (P = .03). Significant correlations of IL-17 with IL-6 (P < .001) and IL-17 with Mcl-1 (P < .001) expression were also observed. Cell growth rate was increased, and IL-17/Mcl-1 expression levels were elevated in HPV 16 E6-transfected H1299 cells. The transfected E6 oncoproteins can significantly up-regulate expression levels of IL 17 and antiapoptotic protein Mcl-1. CONCLUSIONS: The study suggests that HPV infection-induced IL-17 levels can stimulate Mcl-1 expression through the PI3K pathway and promote lung tumor cell progression through a p53- and IL-6 independent pathway. PMID- 20578177 TI - Testicular microlithiasis predicts concurrent testicular germ cell tumors and intratubular germ cell neoplasia of unclassified type in adults: a meta-analysis and systematic review. AB - BACKGROUND: There is an increasing body of literature associating testicular microlithiasis (TM), a common finding on testicular ultrasound, with testicular germ cell tumor (TGCT) and intratubular germ cell neoplasia of unclassified type (ITGCNU). Determining these associations is pertinent both clinically and biologically. To the authors' knowledge, no previous systematic review or meta analysis has been performed. METHODS: A comprehensive systematic literature review was performed without language restrictions through July 2009 and included an exhaustive search of electronic databases and article references. Two reviewers extracted data independently. Studies were categorized according to the clinical context in which sonography was performed. The primary study outcomes were concurrent diagnoses of TGCT or ITGCNU, with TM. In addition, studies with prospective follow-up of patients with TM were reviewed. RESULTS: Thirty-three studies met inclusion criteria. TM was not associated with an increased risk of TGCT in asymptomatic men. However, in referral populations, TM was associated overall with a risk ratio of 8.5 (95% confidence interval [CI], 4.5-16.1; P<.001) for a concurrent diagnosis of TGCT and 10.5 (95% CI, 5.3-20.8; P<.0001) for ITGCNU. Seventeen observational studies were identified in which the interval development of TGCT in patients with TM was reported; however, the majority of those studies did not report the follow-up of a control arm and could not be summarized. CONCLUSIONS: In the presence of risk factors, TM was associated with a substantially elevated risk of a concurrent diagnosis of TGCT and ITGCNU. The authors suggest modifications to recently proposed guidelines for the management of TM. PMID- 20578178 TI - Underuse of colorectal cancer screening among men screened for prostate cancer: a teachable moment? AB - BACKGROUND: Evidence suggests that colorectal cancer (CRC) screening reduces disease-specific mortality, whereas the utility of prostate cancer screening remains uncertain. However, adherence rates for prostate cancer screening and CRC screening are very similar, with population-based studies showing that approximately 50% of eligible US men are adherent to both tests. Among men scheduled to participate in a free prostate cancer screening program, the authors assessed the rates and correlates of CRC screening to determine the utility of this setting for addressing CRC screening nonadherence. METHODS: Participants (N = 331) were 50 to 70 years old with no history of prostate cancer or CRC. Men registered for free prostate cancer screening and completed a telephone interview 1 to 2 weeks before undergoing prostate cancer screening. RESULTS: One half of the participants who underwent free prostate cancer screening were eligible for but nonadherent to CRC screening. Importantly, 76% of the men who were nonadherent to CRC screening had a regular physician and/or health insurance, suggesting that CRC screening adherence was feasible in this group. Furthermore, multivariate analyses indicated that the only significant correlates of CRC screening adherence were having a regular physician, health insurance, and a history of prostate cancer screening. CONCLUSIONS: Free prostate cancer screening programs may provide a teachable moment to increase CRC screening among men who may not have the usual systemic barriers to CRC screening, at a time when they may be very receptive to cancer screening messages. In the United States, a large number of men participate in annual free prostate cancer screening programs and represent an easily accessible and untapped group that can benefit from interventions to increase CRC screening rates. PMID- 20578180 TI - Characteristics of patients with stage III colon adenocarcinoma who fail to receive guideline-recommended treatment. AB - BACKGROUND: Many patients with stage III colon adenocarcinoma do not receive adjuvant chemotherapy despite the proven survival advantage it offers. To enhance the provision of optimal cancer care, patient characteristics associated with not receiving guideline-adherent treatment must be identified among patients with operable, stage III colon adenocarcinoma. METHODS: This was a population-based, retrospective study of all patients who underwent surgery for stage III colon adenocarcinoma diagnosed from 2002 through 2005 in Alberta, Canada. Demographic and treatment information captured in the Alberta Cancer Registry were linked to: 1) hospital discharge data to determine comorbidities, 2) electronic medical records to identify consults with oncologists, and 3) the 2001 Canadian census for neighborhood-level socioeconomic data. Multivariate log-binomial regression models were used to identify patient characteristics that were associated with not having a consultation with a medical oncologist and not receiving adjuvant chemotherapy. RESULTS: Of the 772 patients who underwent surgery for stage III colon adenocarcinoma and met the eligibility criteria, 618 patients (80%) had a consultation with an oncologist. Of those, 388 patients (63%) initiated adjuvant chemotherapy within 84 days of their surgery. Patient characteristics that were associated with not having a consultation with an oncologist were neighborhood income, geography, age, and comorbidities. Of those patients who had a consultation, after adjusting for comorbidities, only older age was related to not receiving adjuvant chemotherapy. CONCLUSIONS: The current results indicated that the proportion of patients with stage III colon adenocarcinoma who did not receive treatment according to evidence-based guidelines was appreciable. The authors concluded that the association of this failure with patient age, geography, and income is concerning and that evaluation of referral patterns and interventions are needed. PMID- 20578179 TI - Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. AB - BACKGROUND: A study was undertaken to analyze the survival of chronic lymphocytic leukemia (CLL) patients relative to age-matched individuals in the general population and determine the age-stratified utility of prognostic testing. METHODS: All 2487 patients diagnosed with CLL between January 1995 and June 2008 and cared for in the Mayo Clinic Division of Hematology were categorized by age at diagnosis and evaluated for differences in clinical characteristics, time to first treatment, and overall survival (OS). RESULTS: Among Rai stage 0 patients, survival was shorter than the age-matched general population for patients aged <55 years (P < .001), 55 to 64 years (P < .001), and 65 to 74 years (P < .001), but not those aged >=75 years at diagnosis (P = not significant). CD38, IGHV mutation, and ZAP-70 each predicted time to first treatment independent of stage for all age groups (all P < .04), but had less value for predicting OS, particularly as age increased. IGHV and fluorescent in situ hybridization (FISH) predicted OS independent of stage for patients aged <55 years (P <= .001), 55 to 64 years (P <= .004), and 65 to 74 years (P <= .001), but not those aged >=75 years. CD38 and ZAP-70 each predicted OS independent of stage for only 2 of 4 age categories. Among Rai 0 patients aged <75 years, survival was shorter than the age-matched population only for IGHV unmutated (P < .001) patients or those with unfavorable FISH (P < .001). CONCLUSIONS: Survival of CLL patients aged <75 years is shorter than the age-matched general population regardless of disease stage. Among patients aged <75 years, the simple combinations of stage and IGHV or stage and FISH identifies those with excess risk of death relative to the age-matched population. Although useful for predicting time to first treatment independent of stage for patients of all ages, prognostic testing had little utility for predicting OS independent of stage among patients aged >=75 years. PMID- 20578182 TI - Regional variation in cancer-directed surgery and mortality among women with epithelial ovarian cancer in the Medicare population. AB - BACKGROUND: Regional differences in health services can point to disparities in access to healthcare. The authors performed a population-based cohort study to examine differences in ovarian cancer treatment and mortality according to geographic region. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify 4589 women aged >=65 years with ovarian cancer diagnosed between 1998 and 2002 who had Medicare claims filed from 1998 to 2005. Hospital Referral Region (HRR) was assigned according to patient zip code. The authors calculated the proportion of women in each HRR who underwent cancer-directed surgery. With HRR as the predictor of interest, mortality and the receipt of cancer-directed surgery were described in multivariate analyses. RESULTS: Among 4589 women with ovarian cancer, 3286 underwent cancer-directed surgery. The receipt of cancer-directed surgery varied by HRR (range, 53%-88%). Women were less likely to undergo cancer-directed surgery if they were older, nonwhite, had higher stage disease, or had more comorbidities. For example, white women were more likely to undergo such surgery (odds ratio, 1.41; 95% confidence interval, 1.10-1.82) compared with all nonwhite women. HRR was a significant predictor of cancer-directed surgery (P = .01). A significant correlation was observed between HRR and all-cause mortality (P = .02); however, after adjusting for cancer-directed surgery, that correlation was no longer significant (P = .10). CONCLUSIONS: There was regional variation in mortality among Medicare recipients with ovarian cancer, and access to cancer directed surgery explained some of that variation. Improving access to high quality cancer surgery for ovarian cancer may improve outcomes, particularly for minorities and for older women. PMID- 20578181 TI - Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development. AB - BACKGROUND: Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, the authors have shown that the tetraspan protein epithelial membrane protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here the authors validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS: A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS: There was a stepwise, statistically significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSIONS: EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate EMP2 as a novel biomarker for EC development. PMID- 20578183 TI - Comparison of simultaneous or delayed liver surgery for limited synchronous colorectal metastases. AB - BACKGROUND: The optimal surgical strategy for patients with synchronous colorectal liver metastases (CLMs) is still unclear. The aim of this study was to compare simultaneous colorectal and hepatic resection with a delayed strategy in patients who had a limited hepatectomy (fewer than three segments). METHODS: All patients with synchronous CLMs who underwent limited hepatectomy between 1990 and 2006 were included retrospectively. Short-term outcome, overall and progression free survival were compared in patients having simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy. RESULTS: Of 228 patients undergoing hepatectomy for synchronous CLMs, 55 (24.1 per cent) had a simultaneous colorectal resection and 173 (75.9 per cent) had delayed hepatectomy. The mortality rate following hepatectomy was similar in the two groups (0 versus 0.6 per cent respectively; P = 0.557), but cumulative morbidity was significantly lower in the simultaneous group (11 per cent versus 25.4 per cent in the delayed group; P = 0.015). Three-year overall and progression-free survival rates were 74 and 8 per cent respectively in the simultaneous group, compared with 70.3 and 26.1 per cent in the delayed group (overall survival: P = 0.871; progression-free survival: P = 0.005). Significantly more recurrences were observed in the simultaneous group at 3 years (85 versus 63.6 per cent; P = 0.002); a simultaneous strategy was an independent predictor of recurrence. CONCLUSION: Combining colorectal resection with a limited hepatectomy is safe in patients with synchronous CLMs and associated with less cumulative morbidity than a delayed procedure. However, the combined strategy has a negative impact on progression-free survival. PMID- 20578184 TI - Nanog regulates primordial germ cell migration through Cxcr4b. AB - Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, such as Oct4 and Nanog, are expressed in PGCs and gonads, suggesting a role for these genes in maintaining pluripotency of the germ lineage, which may be considered the only cell type that perpetually maintains stemness properties. Here, we report that medaka Nanog (Ol-Nanog) is expressed in the developing PGCs. Depletion of Ol-Nanog protein causes aberrant migration of PGCs and inhibits expression of Cxcr4b in PGCs, where it normally serves as the receptor of Sdf1a to guide PGC migration. Moreover, chromatin immunoprecipitation analysis demonstrates that Ol-Nanog protein binds to the promoter region of Cxcr4b, suggesting a direct regulation of Cxcr4b by Ol-Nanog. Simultaneous overexpression of Cxcr4b mRNA and depletion of Ol-Nanog protein in PGCs rescues the migration defective phenotype induced by a loss of Ol-Nanog, whereas overexpression of Sdf1a, the ligand for Cxcr4b, does not restore proper PGC migration. These results indicate that Ol-Nanog mediates PGC migration by regulating Cxcr4b expression. PMID- 20578185 TI - Parental adherence to clinical recommendations in an ADHD evaluation clinic. AB - The present study examined perceived barriers to parental adherence with child psychological assessment recommendations. Eighty caregivers of children referred to an attention-deficit/hyperactivity disorder (ADHD) evaluation clinic completed a telephone interview 4 to 6 weeks after receiving evaluation feedback. Caregivers reported adherence to 81.5% of recommendations and were equally likely to engage in self-help recommendations (i.e., information on ADHD) and those for professional-nonpsychological services (i.e., medication consultation). Caregivers were least likely to follow through on recommendations for psychological services (e.g., parental behavior training, individual therapy for children with symptoms of anxiety/depression). Higher rather than lower levels of parenting stress were associated with greater adherence. The most commonly reported barriers were lack of time and perceptions that the child's teacher was uncooperative with implementing school-based recommendations. PMID- 20578187 TI - Treatment of an iatrogenic subclavian artery dissection. AB - Subclavian artery dissection is a rare complication of cardiac catheterization. The usual reason for entering this vessel is to access the origin of the left internal mammary artery (LIMA) when this has previously been used, or is being considered, as a bypass graft. We report an instance of such dissection occurring long after bypass surgery which had included a LIMA graft. Successful correction was achieved by angioplasty and stent placement, using a retrograde left brachial approach. PMID- 20578186 TI - Assessing suicide risk among callers to crisis hotlines: a confirmatory factor analysis. AB - Our goal was to investigate the factor structure of a risk assessment tool utilized by suicide hotlines and to determine the predictive validity of the obtained factors in predicting subsequent suicidal behavior. We conducted an Exploratory Factor Analysis (EFA), an EFA in a Confirmatory Factor Analysis (EFA/CFA) framework, and a CFA on independent subsamples derived from a total sample of 1,085. Similar to previous studies, we found consistent evidence for a two-factor solution, with one factor representing a more pernicious form of suicide risk (i.e., Resolved Plans and Preparations; RPP) and one factor representing milder suicidal ideation (i.e., Suicidal Desire and Ideation; SDI). The RPP factor trended toward being more predictive of suicidal ideation at follow-up than the SDI factor. PMID- 20578188 TI - Carotid artery stenting in octogenarians using a proximal endovascular occlusion cerebral protection device: a multicenter registry. AB - BACKGROUND: Carotid stenting (CAS) has been proposed as an alternative to carotid endoarterectomy also in elderly patients with discrepant results. However, the use of proximal neuroprotection devices have not been evaluated in octogenarians. PURPOSE: The aim of this multicenter prospective registry was to demonstrate that CAS in octogenarians is safe and effective if performed in high-volume centers by experienced operators. METHODS: From July 2005 to May 2009, a total of 198 octogenarians patients, in three different institutions, were included in this registry. All patients underwent CAS using proximal endovascular occlusion device (Mo.Ma. device Invatec, Roncadelle, Italy). An independent neurologist evaluated all patients. The primary endpoint was death and stroke rate at 30 days. RESULTS: 198 octogenarians (135 men; mean age: 83.2 years) were included in the registry. 39.4% of the patients were symptomatic. Procedural success was 100%. In-hospital complications: Two minor and two major strokes (2.02%) occurred. No device related complications and no serious access site complication were noted. Between discharge and 30-day follow-up, one patient died due to a cardiac arrest. The overall 30-day combined stroke/death rate was 2.52%, resulting in 1.61% event incidence in asymptomatic and 3.9% in symptomatic patients (P = ns). Logistic regression did not identify independent predictor of neurological events, except in the female gender. CONCLUSION: This multicenter prospective registry shows that CAS performed with proximal flow blockage is safe and feasible also in octogenarians. Thirty days death/stroke rates are similar to those of the overall population and within the International guidelines. PMID- 20578189 TI - Appropriate patient and device selection crucial for clinical benefit following renal stenting. PMID- 20578190 TI - Renal artery stenting in patients with chronic ischemic heart disease. AB - OBJECTIVES: To investigate the role of renal stenting in selected patients with chronic ischemic heart disease and renal artery stenosis. METHODS: Consecutive patients, with chronic ischemic heart disease and severe hypertension and/or impaired renal function undergoing renal stenting, were prospectively enrolled. Mid-term (at least 2 years) follow-up was performed to assess both changes in renal function [serum creatinine and estimated glomerular filtrate rate (eGFR)] and blood pressure (BP) control (number of required drugs) and to record the incidence of clinical major adverse events. Moreover, in the first consecutive 24 patients, out-of-range pressure values at 24-hr BP monitoring and GFR at renal scintigraphy were measured at baseline and 1 month after stenting. RESULTS: Seventy patients treated by stenting on 86 renal arteries entered the study. Procedural success rate was 99% and no major complication occurred. At 2-year follow-up, both mean serum creatinine (-0.1 +/- 0.7 mg/dl at follow-up compared to baseline, P = 0.6) and eGFR (+3.7 +/- 23.5 ml/min/1.73m(2) at follow-up compared to baseline, P = 0.2) did not significantly change while the number of drugs required to control BP significantly decreased (2.7 +/- 0.8 to 2.2 +/- 0.7, P < 0.0001). In the subset of 24 patients evaluated at 1 month, GFR significantly increased (62 +/- 20 ml/min to 67 +/- 21 ml/min; P = 0.008) and the rate of the out-of-range systolic pressure values at 24-hr monitoring significantly decreased (51-33%, P = 0.005). Elevated baseline creatinine values and the presence of global renal ischemia were identified as predictors of poor outcome at the multivariate analysis. CONCLUSIONS: In selected patients with chronic ischemic heart disease and hypertension and/or renal insufficiency, renal stenting may be performed with very low periprocedural complications and results in unchanged renal function and improved BP control. PMID- 20578191 TI - Misadventures in the danger zone: subclavian dissections. PMID- 20578192 TI - Outcomes after differential use of drug-eluting stents in diabetic patients: 1 year results from the DES.DE (Drug-Eluting Stent.DEutschland) registry. AB - OBJECTIVES: The prospective multicenter German DES.DE registry provides real world data to evaluate the therapeutic principle of two different drug-eluting stents (DES) [Sirolimus- (SES) and Paclitaxel-eluting stent (PES)] in the context of the German Health System. BACKGROUND: Differential DES have been effective in randomized trials, but their difference in safety and efficacy in diabetic patients has not been well studied. METHODS: Baseline, predefined procedural as well as clinical in-hospital and follow-up events were recorded for all 1,526 diabetic patients. The composite of death, myocardial infarction (MI), and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and target vessel revascularization (TVR) were defined as primary endpoints. RESULTS: Between October 2005 and October 2006, 1,526 diabetic patients, 34.2% of them being insulin-dependent, were enrolled (SES: n = 612; PES: n = 914) at 98 DES.DE sites. Overall, one third of patients were admitted with acute coronary syndrome (ACS) and 70% had multivessel-disease reflecting a real world scenario. With similar baseline clinical and descriptive morphology of coronary artery disease (CAD) in both DES groups, there were no statistical differences in 1-year follow up with respect to rates of overall mortality (5.8% vs. 5.4%), TVR (12.0% vs. 11.3%), overall stent thrombosis (5.6% vs. 4.6%) and MACCE (11.4% vs. 10.3%) between both DES. CONCLUSION: The data collected in DES.DE revealed no differences in clinical outcomes within 1 year between SES and PES in diabetic patients in a "real-world" setting. PMID- 20578193 TI - Which DES for diabetics? Round 1: A draw. Round 2: Everolimus leading? PMID- 20578194 TI - An everolimus-eluting stent versus a paclitaxel-eluting stent in small vessel coronary artery disease: a pooled analysis from the SPIRIT II and SPIRIT III trials. AB - OBJECTIVES: To evaluate the safety and efficacy of the XIENCE V everolimus eluting stent compared to the TAXUS paclitaxel-eluting stent in small vessels. BACKGROUND: The XIENCE V everolimus-eluting stent (EES) has been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularization, but its performance in small coronary arteries has not been investigated. METHODS: In this pooled analysis, we studied a cohort of 541 patients with small coronary vessels (reference diameter <2.765 mm) by using patient and lesion level data from the SPIRIT II and SPIRIT III studies. TAXUS Express (73% of lesions) and TAXUS Liberte (27% of lesions) paclitaxel-eluting stents (PES) were used as controls in SPIRIT II. In SPIRIT III, Taxus Express(2) PES was the control. RESULTS: Mean angiographic in-stent and in-segment late loss was significantly less in the EES group compared with the PES group, (0.15 +/- 0.37 mm vs. 0.30 +/- 0.44 mm; P = 0.011 for in-stent; 0.10 +/- 0.38 mm vs. 0.21 +/- 0.34 mm; P = 0.034 for in-segment). EES also resulted in a significant reduction in composite major adverse cardiac events at 1 year (19/366 [5.2%] vs. 17/159 [10.7%]; P = 0.037), due to fewer non-Q-wave myocardial infarctions and target lesion revascularizations. At 1 year, the rate of non-Q-wave myocardial infarction was significantly lower in the EES group compared with that of the PES group (6/366 [1.6%] vs. 8/159 [5.0%]; P = 0.037). CONCLUSIONS: In patients with small vessel coronary arteries, the XIENCE V EES was superior to the TAXUS PES. PMID- 20578195 TI - Another small step for small vessels. PMID- 20578196 TI - Thrombus aspiration in primary percutaneous coronary intervention in high-risk patients with ST-elevation myocardial infarction: a real-world registry. AB - OBJECTIVES: To evaluate the effect of thrombus aspiration in a real-world all comer patient population with STEMI undergoing primary PCI. BACKGROUND: Catheter thrombus aspiration in primary PCI was beneficial in randomized clinical trials. METHODS: We enrolled 313 STEMI patients presenting with TIMI Flow Grade 0 or 1 in the infarct related artery at baseline angiogram undergoing primary PCI. PATIENTS were divided in two groups based on whether thrombus aspiration was attempted. This decision was left at operator's discretion. Procedural and long-term clinical outcomes were compared between the two groups. RESULTS: Baseline characteristics were similar between groups: 194 (62%) received thrombus aspiration and 119 underwent conventional PCI. Thrombus aspiration was associated with significantly lower post-PCI TIMI Frame Count values (19 +/- 15 vs. 25 +/- 17; P = 0.002) and higher TIMI Flow Grade 3 (92% vs. 73%; P < 0.001). Postprocedural myocardial perfusion assessed by myocardial blush grade (MBG) was significantly increased in the thrombus aspiration group (MBG 3: 44% vs. 21%; P < 0.001). No significant difference was found between the two groups in clinical outcome at 30 days. At one year, patients treated with thrombus aspiration showed significantly higher overall survival (HR 0.41, 95% CI 0.20-0.81; log-rank P = 0.010) and MACE-free survival (HR 0.49, 95% CI 0.28-0.85; log-rank P = 0.011). CONCLUSIONS: In real-world all-comer STEMI patients with occluded infarct-related artery, thrombus aspiration prior to PCI improves coronary flow, myocardial perfusion, and long-term clinical outcome as compared with PCI in the absence of thrombus aspiration. PMID- 20578197 TI - 14q32/miRNA clusters loss of heterozygosity in acute lymphoblastic leukemia is associated with up-regulation of BCL11a. AB - This study evaluated the loss and expression level of miRNAs 14q32 clusters in acute lymphoblastic leukemia (ALL) patients with cryptic deletions at 14q32 chromosomal band to investigate their involvement in this disease. We demonstrate that a subset of ALL cases bearing 14q32 LOH showed a down-regulation of miRNA 14q32 clusters, which is directly linked to the submicroscopic chromosomal deletion. As a consequence of miRNAs deregulation we reported an inverse correlation with the expression of their target BCL11a, a transcription factor involved in lymphoid differentiation. These results suggest that 14q32/miRNA clusters LOH may be another mechanism involved in lymphoid B cell transformation and differentiation and therefore, could be used as a diagnostic marker and therapeutic target in subsets of ALL. PMID- 20578199 TI - Aspiring to aspirate: suck it up. PMID- 20578198 TI - Long term follow-up of allogeneic stem cell transplantation in patients with myelodysplastic syndromes using busulfan, cytosine arabinoside, and cyclophosphamide. AB - We report here the 10-year follow-up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m(2) IV, and cyclophosphamide 120 mg/kg IV. Fifty-nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow-up for survivors of 124 months, the 10-year Kaplan-Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31-53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32-54%) and 19% (95% CI: 11-27%), respectively. No patient relapsed after 2 years. In patients with RAEB-T/AML, 10-year relapse-free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long-term follow-up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse-free and OS with acceptable toxicity in this group of patients with high-risk features. PMID- 20578200 TI - Low CD49d expression and long telomere identify a chronic lymphocytic leukemia subset with highly favourable outcome. PMID- 20578201 TI - Post-transplant lymphoproliferative disorder presenting as multiple myeloma. PMID- 20578202 TI - Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed diabetic patients. AB - BACKGROUND: To evaluate whether intensive insulin therapy leads to changes in macular biometrics (volume and thickness) in newly diagnosed diabetic patients with acute hyperglycaemia and its relationship with serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). METHODS: Twenty-six newly diagnosed diabetic patients admitted to our hospital to initiate intensive insulin treatment were prospectively recruited. Examinations were performed on admission (day 1) and during follow-up (days 3, 10 and 21) and included a questionnaire regarding the presence of blurred vision, standardized refraction measurements and optical coherence tomography. Plasma VEGF and sFlt-1 were assessed by ELISA at baseline and during follow-up. RESULTS: At study entry seven patients (26.9%) complained of blurred vision and five (19.2%) developed burred vision during follow-up. Macular volume and thickness increased significantly (p = 0.008 and p = 0.04, respectively) in the group with blurred vision at day 3 and returned to the baseline value at 10 days. This pattern was present in 18 out of the 24 eyes from patients with blurred vision. By contrast, macular biometrics remained unchanged in the group without blurred vision. We did not detect any significant changes in VEGF levels during follow-up. By contrast, a significant reduction of sFlt-1 was observed in those patients with blurred vision at day 3 (p = 0.03) with normalization by day 10. CONCLUSION: Diabetic patients with blurred vision after starting insulin therapy present a significant transient increase in macular biometrics which is associated with a decrease in circulating sFlt-1. PMID- 20578203 TI - Incidence rates and predictors of diabetes in those with prediabetes: the Strong Heart Study. AB - BACKGROUND: The association between prediabetes as currently defined and incident diabetes in populations with widespread obesity, insulin resistance syndrome, and diabetes is not well defined. In this article, diabetes risk factors and incidence rates in American Indians (AI) with prediabetes are examined. METHODS: A total of 1677 AI who were nondiabetic at baseline was examined during a median 7.8-year follow-up as part of the Strong Heart Study (SHS). Risk factors for incident diabetes were measured. Prediabetes was defined according to American Diabetes Association 2003 criteria as having impaired glucose tolerance (IGT) (2 h plasma glucose [2-h PG] >or= 140 mg/dL but < 200 mg/dL) and/or impaired fasting glucose (IFG) (fasting plasma glucose [FPG] >or= 100 mg/dL but < 126 mg/dL). RESULTS: Prediabetes was identified by FPG alone in 87.5%. Diabetes incidence in those with baseline prediabetes was 66.1/1000 person-years, with a hazard ratio (HR) of 2.35 (95% conference interval: 1.84-3.01), compared with participants with normal glucose tolerance (NGT) at baseline. Elevated A(1c), 2-h PG, and fasting insulin (FI); albuminuria; and obesity were significantly associated with conversion from prediabetes to diabetes. Younger age, elevated FI (or body mass index [BMI] in models without FI), and less physical activity were significantly associated with conversion from NGT. CONCLUSIONS: Prediabetes is an independent predictor of conversion to type 2 diabetes in AI, and most can be identified through a fasting glucose measure. Measures of obesity, A(1c), FPG, 2-h PG, FI, albuminuria, and insulin resistance (IR) help predict this conversion. Obesity is a modifiable risk factor. Strategies to reduce obesity should be emphasized in individuals with prediabetes. PMID- 20578205 TI - Enhanced weight loss with protein-enriched meal replacements in subjects with the metabolic syndrome. AB - BACKGROUND: The objective of this study was to investigate the effects of a protein-rich diet in comparison with a conventional protein diet on weight loss, weight maintenance, and body composition in subjects with the metabolic syndrome. METHODS: Obese subjects received instructions for an energy-restricted diet with a calorie deficit of 500 kcal/day and were randomly assigned to either high protein (1.34 g/kg body weight) or conventional protein (0.8 g/kg body weight) diets for 12 months. Protein-enriched meal replacements were used to enrich one arm of the diet with protein throughout the study. In all, 67% of the participants completed the 1-year study. RESULTS: Subjects following the high protein diet lost more body weight and more fat mass compared with those on the conventional protein diet, whereas the loss of fat-free mass was similar in both diet groups. Biochemical parameters associated with the metabolic syndrome improved in both diet groups. Improvements were modestly greater in subjects with the high-protein diet. After 12 months of treatment, 64.5% of the subjects in the high-protein diet group and 34.8% of the subjects in the conventional diet group no longer met three or more of the criteria for having the metabolic syndrome. CONCLUSIONS: Individuals with the metabolic syndrome achieved significant weight loss while preserving fat-free mass when treated with an energy-restricted, high protein diet that included nutrient-dense meal replacements, as compared with the results for conventional protein intake. An intervention with a protein-enriched diet may have advantages for the management of the metabolic syndrome. PMID- 20578204 TI - Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of impaired fasting glucose in African American and Caucasian adults: the atherosclerosis risk in communities (ARIC) study. AB - BACKGROUND: Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with impaired fasting glucose (IFG) in Caucasians, data from large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on IFG in the context of metabolic risk factors for diabetes. METHODS: We investigated the association between the TCF7L2 rs7903146 polymorphism and incident IFG defined as fasting serum glucose levels of 100-125 mg/dL (5.6-6.9 mmol/L) in 1377 African American and 5152 Caucasian participants without diabetes and IFG at intake who participated in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 to 1989 and were followed for 9 years. RESULTS: Incident IFG was identified in 810 (58.8%) African American and 2652 (51.5%) Caucasian participants. Compared to homozygous CC Caucasian individuals, heterozygous CT [hazard ratio (HR) = 1.09 (95% CI = 1.03-1.15)] and homozygous TT [1.18 (1.05-1.33)] individuals had significantly higher risk of developing IFG over 9-year follow-up. The association between rs7903146 and IFG risk was stronger in Caucasians with obesity [HR(CTvs.CC) = 1.28 (1.12, 1.47); HR(TTvs.CC) = 1.65 (1.25, 2.17)] or high triglycerides [HR(CTvs.CC) = 1.31(1.10, 1.56); HR(TTvs.CC) = 1.72 (1.21, 2.43)]. No association of the TCF7L2 rs7903146 polymorphism and incident IFG was noted in African Americans. CONCLUSIONS: Our study replicates the association between rs7903146 and IFG risk in a population-based, longitudinal cohort of Caucasians but not in African Americans. For the first time, our study provides evidence for interactions between TCF7L2 and metabolic risk factors on the occurrence of IFG in Caucasians. PMID- 20578206 TI - Relationship of glucose regulation to changes in weight: a systematic review and guide to future research. AB - Although weight gain and obesity are risk factors for poor glucose regulation, the relationship, if any, of glucose regulation to changes in weight is not well understood. The purpose of this study was to conduct a systematic review of research examining the relationship of glucose regulation to changes in weight in human-based studies and to provide guidelines for future research in this area. We searched electronic databases and reference sections of relevant articles, including both diabetic and non-diabetic populations, to locate all the literature published before February 2010, and then conducted a systematic review across studies to compare the research designs and findings. The 22 studies meeting our criteria for review generally supported the relationship of glucose regulation to changes in weight. Three studies reported that poor glucose regulation is associated with weight gain; 12 studies concluded that poor glucose regulation is associated with weight loss; 5 showed complex relationships depending on age, sex, or race/ethnicity; and 2 suggested no relationship. The diverse findings may imply that the direction (negative or positive) of the relationship may depend on specific conditions. More research focused on different subpopulations may provide more definitive information supplemental to the current preliminary findings. Recommendations regarding future research in this particular area are provided in the discussion. PMID- 20578207 TI - Association of the fatty acid-binding protein 2 gene Ala54Thr polymorphism with insulin resistance and blood glucose: a meta-analysis in 13451 subjects. AB - BACKGROUND: The results from the published studies on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with insulin resistance and blood glucose are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with insulin resistance and blood glucose. METHODS: We collected data on fasting blood glucose and fasting insulin, 2-h blood glucose (2-h BG) and 2-h insulin (2-h insulin), and homeostasis model assessment insulin resistance index. A dominant model was used for this meta analysis. RESULTS: Thirty-one studies with 13 451 subjects were included in this meta-analysis. The carriers of Thr54 allele have significantly higher homeostasis model assessment insulin resistance index and marginally higher fasting insulin than the non-carriers: standardized mean difference (SMD) = 0.07, 95% confidence interval (CI, 0.02, 0.12), p = 0.007, p(heterogeneity) = 0.19 and SMD = 0.08, 95% CI (-0.01, 0.17), p = 0.07, p(heterogeneity) < 0.00001, respectively. A borderline significant association between the FABP2 Ala54Thr polymorphism and an increased 2-h BG was also detected under the dominant model: SMD = 0.10, 95% CI (0.00, 0.20), p = 0.05, p(heterogeneity) = 0.09. In addition, a borderline association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins was detected under the dominant model: SMD = 0.11, 95% CI (-0.00, 0.23), p = 0.06, p(heterogeneity) = 0.03. CONCLUSIONS: Our meta-analysis suggests that the Thr54 allele of the FABP2 Ala54Thr is weakly associated with a higher degree of insulin resistance, higher level of fasting insulin and higher level of 2-h BG. Our meta-analysis also suggests a weak association between this polymorphism and an increased fasting blood glucose in populations of other ethnic origins under the dominant model. PMID- 20578208 TI - Binding of licarbazepine enantiomers to mouse and human plasma proteins. AB - Racemic licarbazepine (Lic) is the active metabolite of oxcarbazepine (OXC) and eslicarbazepine acetate (ESL), appearing in human plasma as S-licarbazepine (S Lic) and R-licarbazepine (R-Lic). However, human metabolism of OXC and ESL to Lic differs in the S-Lic/R-Lic enantiomeric ratio observed in plasma. S-Lic appears in higher proportion after ESL administration than after OXC (95% versus 80%). Enantioselective pharmacokinetics of Lic enantiomers have been found in mice after their separate administration and in humans following OXC treatment. Since protein binding of drugs may be enantioselective and a determining factor of pharmacokinetics, the binding of S-Lic and R-Lic to mouse and human total plasma proteins and, specifically, to human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) were herein investigated for the first time. Free and bound fractions of S-Lic and R-Lic were separated by ultrafiltration after previous in vitro incubation of spiked plasma samples and protein solutions with each enantiomer at 10, 25 and 50 microg/ml. The results revealed that the extent of binding of Lic enantiomers to total plasma proteins was 30% and independent of the drug concentration and species considered. The data also suggest that the binding of Lic enantiomers to HSA is greater than that to AGP. Moreover, absence of enantioselectivity in the binding of Lic enantiomers to mouse and human plasma proteins and to HSA and AGP is evident. In conclusion, these findings suggest that the enantioselectivity observed in vivo in the biodisposition of S-Lic and R Lic is not dependent on their affinity to plasma proteins. PMID- 20578209 TI - Sotrastaurin and cyclosporine drug interaction study in healthy subjects. AB - INTRODUCTION: Sotrastaurin is an immunosuppressant that inhibits protein kinase C and blocks T-lymphocyte activation. The authors determined the effect of combining sotrastaurin with the calcineurin inhibitor cyclosporine on the pharmacokinetics and biomarker responses to both drugs. METHODS: This was a randomized, 4-period, crossover study in 20 healthy subjects who received single oral doses of (1) sotrastaurin 100 mg, (2) cyclosporine 400 mg, (3) 100 mg sotrastaurin with 100 mg cyclosporine and (4) 100 mg sotrastaurin with 400 mg cyclosporine. Blood samples were collected to measure drug levels and biomarkers of T-lymphocyte activation (interleukin-2 and tumor necrosis factor producing T cells and interleukin-2 messenger RNA levels) and of T-lymphocyte proliferation (thymidine uptake). RESULTS: Sotrastaurin did not alter cyclosporine AUC; however, low-dose and high-dose cyclosporine increased sotrastaurin AUC by 1.2 fold [90% confidence interval, 1.1-1.4] and 1.8-fold [1.6-2.1], respectively. Adding high-dose cyclosporine to a low-therapeutic dose of sotrastaurin significantly enhanced the inhibition of cytokine production by 31% [95% confidence interval, 25-36%], of interleukin-2 messenger RNA levels by 13% [7 19%], and of thymidine uptake by 37% [32-42%] compared with sotrastaurin alone. Addition of low-dose cyclosporine elicited slightly lower enhancements in inhibition by 21% [14-28%], 6% [-4-16%], and 26% [21-30%], respectively, compared with sotrastaurin alone. CONCLUSIONS: Sotrastaurin did not alter the pharmacokinetics of cyclosporine, but cyclosporine increased sotrastaurin AUC up to 1.8-fold. The combined drugs elicited a significantly greater inhibition of T cell activation and proliferation than sotrastaurin alone. PMID- 20578210 TI - Interrelations between plasma caffeine concentrations and neurobehavioural effects in healthy volunteers: model analysis using NONMEM. AB - The objective was to develop a population pharmacokinetic-pharmacodynamic model of caffeine's psychomotor effects in healthy, non-habitual users of caffeine. Twenty Chinese males each received a single dose of 250 mg of caffeine orally. Plasma concentrations of caffeine were determined at various times within 24 h after dosing. The subjects' psychomotor performance was evaluated before and at various times after dosing by a test battery consisting of oculomotor assessment (saccadic velocity) as well as the computerised Swedish Performance Evaluation System. Nonlinear mixed-effects modelling to analyse the pharmacokinetic pharmacodynamic relationships was performed using NONMEM. Model robustness was assessed by a nonparametric bootstrap. The results showed that caffeine caused significant improvements in psychomotor functioning. The time course of these effects was best described by pharmacokinetic/pharmacodynamic models involving an effect compartment. The transfer half-lives between plasma and effect site for different domains of psychomotor functioning were in the range 24.8-49.5 min. Evaluation of the final models showed close agreement between pairs of bootstrapped and final model parameter estimates (all differences<10%). These results provided the first suggestive evidence that caffeine effects on psychomotor performance occur after some time delay relative to changes in plasma caffeine concentration. The models for the neurobehavioural tests provided similar transfer half-lives between plasma and effect site. PMID- 20578211 TI - Dose-dependent pharmacokinetics of SP-8203 in rats. AB - The pharmacokinetics of SP-8203, a potential protective agent for the treatment of cerebral infarction, were evaluated after its intravenous (10, 20 and 30 mg/kg) and oral (10, 20, 30 and 100 mg/kg) administration in rats. After the intravenous administration of SP-8203, the AUCs of SP-8203 were dose-dependent; the dose-normalized AUCs were significantly greater with increasing doses. After the oral administration of SP-8203, plasma concentrations of SP-8203 were much lower than those after intravenous administration. This could be due to considerable hepatic and intestinal metabolism and the high percent of the dose recovered from the gastrointestinal tract (including its contents and feces) at 24 h as unchanged drug. PMID- 20578212 TI - Time-dependent clearance and hematological pharmacodynamics upon erythropoietin multiple dosing in rats. AB - The pharmacokinetics (PK) and pharmacodynamics (PD) of recombinant human erythropoietin (rHuEPO) upon its repeated administrations were investigated. Two groups (A and B) of normal Wistar rats received rHuEPO intravenously at 450 or 1350 IU/kg thrice weekly for 2 and 6 weeks. PK studies were conducted following days 0 and 4 for group (A) and days 0, 17 and 28 for group (B), then, washout PK were assessed on days 11 and 36 for both groups. Reticulocytes (RET), red blood cells (RBC) and hemoglobin (Hb) were evaluated daily until day 14, then every 2 days until day 30 for group (A) and 59 for group (B). The total clearance CL(Total) increased with the dose but decreased over time. Its decay reached 20% and 55% between the first and last full PK in both treatment arms. RET peaked on day 5 and were 77.6% and 87.3% higher than baselines for the two dosing regimen. Their nadirs occurred on days 22 and 55 and were 37.9% and 47.3% below normal values. Hb peaked on days 10 and 34 and was 28.9% and 38.6% above the baseline level, its nadirs occurred on days 25 and 57 and were 13.1% and 16% below baselines. Control animals showed stable baselines over the study but with moderate variability. In conclusion, rHuEPO exhibits a nonlinear PK with a time dependent decrease of its CL(Total). During exposure, RET, RBC and Hb showed a tolerance effect. After exposure, the rebound was characterized for RET, RBC, but not Hb. PMID- 20578213 TI - Validation of a differential in situ perfusion method with mesenteric blood sampling in rats for intestinal drug interaction profiling. AB - The present study explored the feasibility of a differential setup for the in situ perfusion technique with mesenteric cannulation in rats to assess drug interactions at the level of intestinal absorption. In contrast to the classic, parallel in situ perfusion setup, the differential approach aims to identify intestinal drug interactions in individual animals by exposing the perfused segment to a sequence of multiple conditions. First, the setup was validated by assessing the interaction between the P-glycoprotein (P-gp) inhibitor verapamil and the transport probes atenolol (paracellular transport), propranolol (transcellular) and talinolol (P-gp mediated efflux). While transport of atenolol and propranolol remained constant for the total perfusion time (2 h), a verapamil induced increase in talinolol transport was observed within individual rats (between 3.2- and 5.2-fold). In comparison with the parallel setup, the differential in situ perfusion approach enhances the power to detect drug interactions with compounds that exhibit strong subject-dependent permeability. This was demonstrated by identifying an interaction between amprenavir and ketoconazole (P-gp and CYP3A inhibitor) in five out of seven rats (permeability increase between 1.9- and 4.2-fold), despite high inter-individual differences in intrinsic permeability for amprenavir. In combination with an increased throughput (up to 300%) and a reduced animal use (up to 50%), the enhanced power of the differential approach improves the utility of the biorelevant in situ perfusion technique with mesenteric blood sampling to elucidate the intestinal interaction profile of drugs and drug candidates. PMID- 20578214 TI - Thromboelastographic and pharmacokinetic profiles of micro- and macro-emulsions of propofol in swine. AB - PURPOSE: Compared with traditional macroemulsion propofol formulations currently in clinical use, microemulsion formulations of this common intravenous anesthetic may offer advantages. The pharmacokinetics and coagulation effects as assessed by thromboelastography of these formulations were characterized in swine. METHODS: Yorkshire swine (20-30 kg, either sex, n=15) were sedated, anesthetized with isoflurane, and instrumented to obtain a tracheostomy, internal jugular access and carotid artery catheterization. Propofol (2 mg/kg, 30 s) was administered as a macroemulsion (10 mg/ml; Diprivan; n=7) or a custom (2 mg/kg, 30 s) microemulsion (10 mg/ml; n=8). Arterial blood specimens acquired pre- and post injection (1 and 45 min) were used for thromboelastography. Arterial blood specimens (n=12 samples/subject, 60 min) were serially collected, centrifuged and analysed with solid-phase extraction with UPLC to determine propofol plasma concentrations. Non-compartmental pharmacokinetic analysis was applied to plasma concentrations. RESULTS: No changes were noted in the thromboelastographic R time (p=0.74), K time (p=0.41), alpha angle (p=0.97), or maximal amplitude (p=0.71) for either propofol preparation. Pharmacokinetic parameters k (p=0.45), t(1/2) (p=0.26), C(o) (p=0.89), AUC(0-infinity) (p=0.23), CL (p=0.14), MRT (p=0.47), V(ss) (p=0.11) of the two formulations were not significantly different. CONCLUSION: The microemulsion and macroemulsion propofol formulations had similar pharmacokinetics and did not modify thromboelastographic parameters in swine. PMID- 20578215 TI - Do proton pump inhibitors decrease calcium absorption? AB - Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40 mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58 +/- 7 years (mean +/- SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean +/- SD) was 20% +/- 10% at visit 1, 18% +/- 10% at visit 2, and 23% +/- 10% following 30 +/- 3 days of daily omeprazole (p = .07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D(3) level at visit 2 was the only variable (p = .049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture. PMID- 20578216 TI - Estrogen receptor alpha36 mediates a bone-sparing effect of 17beta-estrodiol in postmenopausal women. AB - Recently, a membrane-based estrogen receptor (ER), ER-alpha36, was identified and cloned that transduces membrane-initiated estrogen signaling such as activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show that the postmenopausal level of estradiol (E2) induces mitogenic, antiapoptotic, and antiosteogenic effects and proapoptotic effects in postmenopausal osteoblasts and osteoclasts with high levels of ER-alpha36 expression, respectively. We also found that ER-alpha36 mediated the effects of postmenopausal-level E(2) on proliferation, apoptosis, and differentiation of osteoblasts through transient activation of the MAPK/ERK pathway, whereas ER-alpha36-mediated postmenopausal-level E(2) induces apoptosis of osteoclasts through prolonged activation of the MAPK/ERK pathway with the involvement of reactive oxygen species. We also show that the levels of ER alpha36 expression in bone are positively associated with bone mineral density but negatively associated with bone biochemical markers in postmenopausal women. Thus the higher levels of ER-alpha36 expression are required for preserving bone mass in postmenopausal and menopausal women who become osteoporotic if ER-alpha36 mediated activities are dysregulated. PMID- 20578218 TI - Old is the new new. PMID- 20578219 TI - Closing one hole leads to another: delayed aortic perforation following closure of a patent foramen ovale. PMID- 20578217 TI - Mechanical induction of PGE2 in osteocytes blocks glucocorticoid-induced apoptosis through both the beta-catenin and PKA pathways. AB - Glucocorticoids are known to induce osteocyte apoptosis, whereas mechanical loading has been shown to sustain osteocyte viability. Here we show that mechanical loading in the form of fluid-flow shear stress blocks dexamethasone induced apoptosis of osteocyte-like cells (MLO-Y4). Prostaglandin E(2) (PGE(2) ), a rapidly induced signaling molecule produced by osteocytes, was shown to be protective against dexamethasone-induced apoptosis, whereas indomethacin reversed the antiapoptotic effects of shear stress. This protective effect of shear stress was mediated through EP2 and EP4 receptors, leading to activation of the cAMP/protein kinase A signaling pathway. Activation of phosphatidylinositol 3 kinase, an inhibitor of glycogen synthesis kinase 3, also occurred, leading to the nuclear translocation of beta-catenin, an important signal transducer of the Wnt signaling pathway. Both shear stress and prostaglandin increased the phosphorylation of glycogen synthesis kinase 3 alpha/beta. Lithium chloride, an activator of the Wnt pathway, also was protective against glucocorticoid-induced apoptosis. Whereas it is known that mechanical loading increases cyclooxygenase-2 and EP2 receptor expression and prostaglandin production, dexamethasone was shown to inhibit expression of these components of the prostaglandin pathway and to reduce beta-catenin protein expression. beta-catenin siRNA knockdown experiments abrogated the protective effects of PGE(2), confirming the central role of beta catenin in mediating the protection against dexamethasone-induced cell death. Our data support a central role for PGE(2) acting through the cAMP/PKA and beta catenin signaling pathways in the protection of osteocyte apoptosis by fluid-flow shear stress. PMID- 20578220 TI - Fick simple-shunt hard: simple shunts commentary. PMID- 20578221 TI - Second device for a patent foramen ovale: life saver and psychotherapy. PMID- 20578223 TI - A novel gelatin sponge for accelerated hemostasis. AB - To more effectively manage the substantial bleeding encountered during surgical procedures in oto-rhino-laryngology, we developed a novel hemostatic sponge made of pharmaceutical grade, chemically cross-linked gelatin. The sponge is characterized by a high pore density, reduced ligaments, and a high nanoscale roughness of lamella surfaces in the matrix. In vitro blood uptake assays revealed a very rapid absorption of human blood, which was two to three times faster than that measured with comparative hemostyptic devices. In an in vitro hemorrhage model using human veins, the novel gelatin sponge matrix induced hemostasis less than a minute after bleeding was induced. The sponge was shown to bring about rapid hemostasis when it was administered in a young patient suffering from acute bleeding of a pharyngeal angiofibroma, even though the patient had been treated with an anticoagulant because of a transient ischemic attack. As the gelatin matrix of the sponge is biocompatible and resorbable, the hemostyptic device could be left in place and was shown to be resorbed within 2 weeks. We hypothesize that the excellent hemostatic performance of the sponge might be linked to enhanced capillary effects in conjunction with optimized anchoring of fibrinogen on the nano-rough material surface, as suggested by scanning electron microscopy. The novel gelatin sponge appears to be a promising hemostatic matrix, which could be of great benefit for patients suffering from epistaxis and other acute injuries resulting in severe bleeding. PMID- 20578224 TI - Endovenous therapy for deep venous thrombosis: the TORPEDO trial. AB - OBJECTIVES: We compared the efficacy and safety of percutaneous endovenous intervention (PEVI) plus anticoagulation with anticoagulation alone in the reduction of venous thromboembolism (VTE) and post-thrombotic syndrome (PTS) in acute proximal deep venous thrombosis (DVT). BACKGROUND: Recurrent VTE and PTS are common complications of DVT. There are no randomized trials investigating the efficacy of PEVI in the reduction of the above complications. METHODS: Patients with symptomatic proximal DVT were randomized to receive PEVI plus anticoagulation or anticoagulation alone. Anticoagulation consisted of intravenous unfractionated heparin or subcutaneous low-molecular weight heparin plus warfarin. PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, or local low-dose thrombolytic therapy. RESULTS: At 6 months follow-up, recurrent VTE developed in 2 of 88 patients of the PEVI plus anticoagulation group versus 12 of 81of the anticoagulation-alone group (2.3% vs. 14.8%, P = 0.003). PTS developed in 3 of 88 patients of the PEVI plus anticoagulation Group and 22 of 81 of the anticoagulation-alone group (3.4% vs. 27.2%, P < 0.001). CONCLUSIONS: In patients with symptomatic proximal DVT, PEVI plus anticoagulation may be superior to anticoagulation-alone in the reduction of VTE and PTS at 6 months. PMID- 20578225 TI - Ni-Cr-Co alloy ureteral stent: scanning electron microscopy and elemental analysis characterization after long-term indwelling. AB - We report the first preliminary study on metal-alloy ureteral stent after long indwelling times. The aim is to analyze by physical-chemical characterization of the stent after use and to evaluate the material performance in this human in vivo case study. Six Resonance metallic stents (Cook Ireland) were inserted in six patients for 6, 10, 11, 12, 24, and 36 months. The stents were then collected and studied by Field Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive Spectroscopy (EDS), gaining information about the metal stent surface and the amount and nature of the formed encrustation. The stents were all draining adequately, despite the presence of the bacterial biofilm layer in all stents. This layer was more dense and compact as the indwelling time increased. Some slight precipitation of inorganic compounds, such as brushite and calcium oxalate was observed. No epithelial tissue in growth was recorded. These preliminary results with Resonance metallic ureteral stents suggest the feasibility of a long-term approach in patients with chronic ureteral obstruction. The durability of the metal stent, the lack of epithelial tissue ingrowths and limited pain or discomfort to patients were proven over long time periods. The long-term use of these stents is therefore feasible, avoiding the continuous exchange of the stent, decreasing hospital costs and increasing the quality of life of patients affected by malignant pelvic tumors. PMID- 20578226 TI - Effect of various sterilization methods on the bioactivity of laser ablation pseudowollastonite coating. AB - Sterilization is required for using any material or device in contact with the human body. The aim of this work was to investigate the effect of four sterilization methods (steam autoclave, hydrogen peroxide plasma, ethylene oxide, and gamma sterilization) on the surface chemistry and in vitro bioactivity of pseudowollastonite (psW) coatings in titanium alloys substrates. psW coatings in Ti-6Al-4V substrates obtained by laser ablation technique were sterilized and immersed in Kokubo's simulated body fluid (SBF) up to 30 days. No changes in the chemical composition were noted after sterilization. However, a Ca/P-layer of different thickness, identified as hydroxyapatite (HA) like was developed on all the samples after soaking, although, the ethylene oxide sterilized samples present a nonhomogeneous and approximately 55.9% thinner HA-like layer. PMID- 20578227 TI - Small peptide (P-15) bone substitute efficacy in a rabbit cancellous bone model. AB - P-15 is a synthetic 15-amino acid residue identical to the cell binding domain of type I collagen. P-15 can be adsorbed onto anorganic bovine bone mineral (ABM) and will enhance cell attachment and subsequent cell activation. Although ABM/P 15 has been studied as a bone graft substitute in the oral cavity, its use in orthopedic models has been limited. Thus, this study investigated the efficacy of ABM/P-15 treatment in a rabbit model of long bone cancellous healing. Defects were created in the distal femurs and proximal medial tibiae of rabbits and were filled with either ABMP/P-15 suspended in hydrogel, ABM alone suspended in hydrogel, hydrogel carrier alone, or no graft material. Rabbits were sacrificed at 1, 2, 4, or 8 weeks postsurgery, and the femurs and tibiae were harvested. Histomorphometric analyses indicated that defects treated with ABM/P-15 had significantly larger areas of new bone formation than the other three treatments at 2 and 8 weeks postsurgery. ABM/P-15 treated defects also had significantly more bone growth than defects left empty or filled with ABM alone at 4 weeks postsurgery. Furthermore, histological examination did not reveal acute inflammatory infiltrate cells in any of the treatment conditions. These results are consistent with the findings of ABM/P-15 use in human oral-maxillofacial studies and in large animal spine fusion models. PMID- 20578228 TI - Microscopic versus endoscopic pituitary surgery: a systematic review. AB - OBJECTIVES/HYPOTHESIS: To critically review current literature comparing microscopic versus endoscopic surgery in the treatment of pituitary adenomas. STUDY DESIGN: Systematic review of the literature. METHODS: All English language literature published between January 1989 and June 2009 on PubMed were eligible for inclusion. Inclusion criteria were: direct comparison between microscopic and fully endoscopic approaches and surgery performed with the intent to treat a pituitary adenoma. Endoscopic-assisted comparisons and studies comparing outcomes with previous literature were excluded. Technical notes, case reports, letters, and comments were also excluded. Included studies were categorized according to level of evidence and evaluated for quality using a modified Downs and Black scale. Data was extracted and compared between studies. RESULTS: Of the 3,586 studies retrieved from the search strategy, 11 studies met the inclusion and exclusion criteria. Various outcomes measures were used including: operating time, extent of tumor resection, postoperative normalization of hormone levels, incidence of complications, length of hospital stay, and patient pain and discomfort. The endoscopic approach decreased operating time, lumbar drains, immediate postoperative diabetes insipidus, some rhinologic complications, length of hospital stay, and patient pain and discomfort. Other outcome measures were comparable between the two approaches. CONCLUSIONS: The literature comparing endoscopic and microscopic pituitary surgery favors the endoscopic approach for pituitary surgery. Major outcome measures (extent of tumor resection, changes in hormone levels) do not differ between the two approaches. Complications, time in the operating room and hospital, and patient discomfort are significantly less with the endoscopic approach. PMID- 20578229 TI - Materials characterization of explanted polypropylene, polyethylene terephthalate, and expanded polytetrafluoroethylene composites: spectral and thermal analysis. AB - This study utilized spectral and thermal analysis of explanted hernia mesh materials to determine material inertness and elucidate reasons for hernia mesh explantation. Composite mesh materials, comprised of polypropylene (PP) and expanded polytetrafluoroethylene (ePTFE) mesh surrounded by a polyethylene terephthalate (PET) ring, were explanted from humans. Scanning electron microscopy (SEM) was conducted to visually observe material defects while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used to find chemical signs of surface degradation. Modulated differential scanning calorimetry (MDSC) and thermogravimetric analysis (TGA) gave thermal stability profiles that showed changes in heat of fusion and rate of percent weight loss, respectively. ATR-FTIR scans showed higher carbonyl peak areas as compared to pristine for 91% and 55% of ePTFE and PP explants, respectively. Ninety-one percent of ePTFE explants also exhibited higher C--H stretch peak areas. Seventy-three percent of ePTFE explants had higher heats of fusion while 64% of PP explants had lower heats of fusion with respect to their corresponding pristines. Only 9% of PET explants exhibited a lower heat of fusion than pristine. Seventy-three percent of ePTFE explants, 73% of PP explants, and only 18% of PET explants showed a decreased rate of percent weight loss as compared to pristine. The majority of the PP and ePTFE mesh explants demonstrated oxidation and crosslinking, respectively, while the PET ring exhibited breakdown at the sites of high stress. The results showed that all three materials exhibited varied degrees of chemical degradation suggesting that a lack of inertness in vivo contributes to hernia mesh failure. PMID- 20578230 TI - Lower airways may also be affected in asymptomatic patients with recent onset of allergic rhinitis. AB - OBJECTIVES/HYPOTHESIS: It is well known that there is a close association between allergic rhinitis (AR) and asthma, and AR is a strong risk factor for the onset of asthma. AR duration is significantly associated with a possible bronchial involvement. The aim of this study was to investigate the presence of possible spirometric abnormalities and bronchial hyperreactivity (BHR) in a large group of patients with recent onset of AR. STUDY DESIGN: Observational cross-sectional study. METHODS: A total of 1,539 AR patients were consecutively evaluated. Clinical examination, skin prick test, spirometry, and methacholine challenge were performed on all patients. RESULTS: : There were 362 (23%) patients with FEF(25-75) values <70% of predicted. The methacholine challenge was positive in 74.43% of patients, and 72.22% of the population presented a polysensitization. At multivariable analysis, an FEV(1) value lower than 92% of predicted, as well as increasing severity of BHR and polysensitization appeared to be independent predictors of a reduced FEF(25-75) value. CONCLUSIONS: This study shows that reduced FEF(25-75) values may be present in some patients with recent onset of AR. FEV(1) <92%, severity of BHR, and polysensitization may be considered risk factor for this phenomenon. PMID- 20578231 TI - Defining milestones toward competency in mastoidectomy using a skills assessment paradigm. AB - OBJECTIVES/HYPOTHESIS: To establish milestones toward achievement of surgical competency by using an objective assessment tool designed to measure the development of mastoidectomy skills in the operating room (OR). STUDY DESIGN: Prospective longitudinal validation study. METHODS: Fifty-six evaluations were conducted in the OR on nine otolaryngology residents from PGY (postgraduate year) 2 to PGY 5 over a period of 3 years. Technical performance was measured over time using a task-based checklist developed for assessment of mastoidectomy skills. RESULTS: Three sets of technical milestones represented achievement of competency for progressively more complicated procedural steps: the first set was achieved after a mean of 6 +/- 4.3 cases, the second set after 9 +/- 6.7 cases (range of mean = 8-10 cases), and the third set after 13 +/- 6.4 cases (range of mean = 12 14 cases). CONCLUSIONS: The acquisition of mastoidectomy skills can be integrated into surgical teaching in the OR, and this approach yields information that can aid individual skill development and program improvement. The identification of milestones in particular can help establish training benchmarks toward achievement of competency and in identifying trainees in need of remediation. PMID- 20578232 TI - Influence of topical antifungal drugs on ciliary beat frequency of human nasal mucosa: an in vitro study. AB - OBJECTIVES/HYPOTHESIS: Topical antifungal treatment is a subject of discussion in the treatment of chronic rhinosinusitis. The aim of this research was to study the effects of antifungal drugs on ciliary beat frequency (CBF) of human nasal mucosa under in vitro conditions. STUDY DESIGN: Case series of in vitro experiments and in vitro study of cultured ciliated cells of human nasal mucosa. METHODS: Human nasal mucosa was acquired during routine endoscopic sinus surgery. Cells were cultivated on object slides and exposed to different antifungal drugs in a newly developed test system. This system allowed continuous and reproducible exposure to different drugs at constant temperature, pH value, and osmolarity. The drugs were amphotericin B in two different concentrations and itraconazole. RESULTS: Rinsing with higher concentrations of amphotericin B led to an immediate decrease of CBF, with a total stop after 15 minutes. A different result was seen in the group with lower concentrations; CBF decreased again quickly after rinsing with the test drug, but all of them recovered after rinsing with neutral solution. When using itraconazole a decline in CBF was observed again; one half of the samples returned to activity. CONCLUSIONS: Our in vitro results demonstrate a dose-dependent effect of the antifungal drugs amphotericin B and itraconazole on ciliary beat frequency of human nose epithelium. PMID- 20578233 TI - Design and validation of a metabolic disorder resequencing microarray (BRUM1). AB - The molecular genetic diagnosis of inherited metabolic disorders is challenging. The diseases are rare, and most show locus heterogeneity. Hence, testing of the genes associated with IMDs is time consuming and often not easily available. We report a resequencing array that allows the simultaneous resequencing of up to 92 genes associated with IMDs. To validate the array, DNA samples from 51 patients with 52 different known variants (including point variants, small insertion, and deletions [indels]) in seven genes (C14ORF133, GAA, NPC1, NPC2, VPS33B, WFS1, and SLC19A2) were amplified by PCR and hybridized to the array. A further patient cohort with 48 different mutations in NPC1 were analyzed blind. Out of 76 point variants, 73 were identified using automated software analysis followed by manual review. Ten insertion and deletion variants were detected in the extra tiling using mutation specific probes, with 11 heterozygous deletions and 3 heterozygous insertions. In summary, we identified 96% (95% confidence interval [CI] 89-99%) of point variants added to the array, but the pickup rate reduced to 83% (95% CI 75-89%) when insertions/deletions were included. Although the methodology has strengths and weaknesses, application of this technique could expedite diagnosis in most patients with multilocus IMDs. PMID- 20578234 TI - Cardiac progenitor cells: potency and control. AB - Stem cell-based regeneration of the heart has focused much scientific and public attention being cardiac diseases the major cause of disability and death in industrialized countries. Innumerable efforts have been taken to unveil the mechanisms undergoing stem cell proliferation and fate, but much remains to be endeavoured for their application in clinical practice. Nevertheless, the discovery of progenitor cells resident within the cardiac tissue has sparked off enthusiasm about the possibility of efficiently and safely engineering them to repair the injured myocardium. Indeed, the early applications of the cardiac progenitor cells, mostly based on simplistic concepts and techniques, have failed highlighting the prerequisite of expanding the knowledge about progenitor cell features and microenvironmental conditioning. In this review, recent information on resident cardiac progenitor cells has been systematically gathered in order to create a valuable instrument to support investigators in their efforts to establish an efficient cardiac cell therapy. PMID- 20578235 TI - Intestinal stem cell asymmetric division in the Drosophila posterior midgut. AB - Over the past 2 years, our understanding of intestinal stem cells in the Drosophila posterior midgut has advanced greatly. In this review, I will focus on the establishment of these stem cells in their niche during development and the molecular mechanisms that regulate their asymmetric division in adults. PMID- 20578236 TI - Thyroid tumor marker genomics and proteomics: diagnostic and clinical implications. AB - Two systems biology concepts, genomics and proteomics, are highlighted in this review. These techniques are implemented to optimize the use of thyroid tumor markers (TTM). Tissue microarray studies can produce genetic maps and proteomics, patterns of protein expression of TTM derived from preoperative biopsies and specimens. For instance, papillary and medullary thyroid cancers harbor RAS, RET, and BRAF genetic mutations. Follicular thyroid cancers harbor translocations and fusions of certain genes (PAX 8 and PPAR-gamma). Proteomic analysis from various tissue sources can provide useful information regarding the overall state of a thyroid cancer cell. Understanding the molecular events related to these genetic and protein alterations can potentially clarify thyroid cancer pathogenesis and guide appropriate molecular targeted therapies. However, despite the realization that these emerging technologies hold great promise, there are still significant obstacles to the routine use of TTM. These include equivocal thyroid nodule tissue morphologic interpretations, inadequate standardization of methods, and monetary costs. Interpretative shortcomings are frequently due to the relative scarcity of cellular material from fine-needle aspiration biopsy (FNAB) specimens. This can be rectified with large needle aspiration biopsy (LNAB) techniques and is exemplified by the favorable performance of galectin-3 determinations on LNAB specimens. PMID- 20578237 TI - Sickle cell anemia and vascular dysfunction: the nitric oxide connection. AB - Endothelial dysfunction and impaired nitric oxide bioavailability have been implicated in the pathogenesis of sickle cell anemia. Nitric oxide is a diatomic gas with a role in vascular homeostasis. Hemoglobin polymerization resulting from the HbS mutation produces erythrocyte deformation and hemolysis. Free hemoglobin, released into plasma by hemolysis scavenges on nitric oxide, and leads to reduced nitric oxide bioavailability. Pulmonary hypertension is a known consequence of sickle cell anemia. It occurs in 30-40% of patients with sickle cell anemia, and is associated with increased mortality. Several studies have implicated intravascular hemolysis, and impaired nitric oxide bioavailability in the pathogenesis of pulmonary hypertension. In this review, we summarize the mechanisms of altered nitric oxide bioavailability in sickle cell anemia and its possible role in the pathogenesis of pulmonary hypertension. PMID- 20578238 TI - Redistribution of mitochondria leads to bursts of ATP production during spontaneous mouse oocyte maturation. AB - During mammalian oocyte maturation there are marked changes in the distribution of mitochondria that supply the majority of the cellular ATP. Such redistribution of mitochondria is critical for oocyte quality, as oocytes with a poor developmental potential display aberrant mitochondrial distribution and lower ATP levels. Here we have investigated the dynamics of mitochondrial ATP production throughout spontaneous mouse oocyte maturation, using live measurements of cytosolic and mitochondrial ATP levels. We have observed three distinct increases in cytosolic ATP levels temporally associated with discrete events of oocyte maturation. These changes in cytosolic ATP levels are mirrored by changes in mitochondrial ATP levels, suggesting that mitochondrial ATP production is stimulated during oocyte maturation. Strikingly, these changes in ATP levels correlate with the distribution of mitochondria undergoing translocation to the peri-nuclear region and aggregation into clusters. Mitochondrial clustering during oocyte maturation was concomitant with the formation of long cortical microfilaments and could be disrupted by cytochalasin B treatment. Furthermore, the ATP production bursts observed during oocyte maturation were also inhibited by cytochalasin B suggesting that mitochondrial ATP production is stimulated during oocyte maturation by microfilament-driven, sub-cellular targeting of mitochondria. PMID- 20578239 TI - Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer. AB - Multifunctional macrophage inhibitory cytokine-1, MIC-1, is a member of the transforming growth factor-beta (TGF-beta) superfamily that plays key roles in the prenatal development and regulation of the cellular responses to stress signals and inflammation and tissue repair after acute injuries in adult life. The stringent control of the MIC-1 expression, secretion, and functions involves complex regulatory mechanisms and the interplay of other growth factor signaling networks that control the cell behavior. The deregulation of MIC-1 expression and signaling pathways has been associated with diverse human diseases and cancer progression. The MIC-1 expression levels substantially increase in cancer cells, serum, and/or cerebrospinal fluid during the progression of diverse human aggressive cancers, such as intracranial brain tumors, melanoma, and lung, gastrointestinal, pancreatic, colorectal, prostate, and breast epithelial cancers. Of clinical interest, an enhanced MIC-1 expression has been positively correlated with poor prognosis and patient survival. Secreted MIC-1 cytokine, like the TGF-beta prototypic member of the superfamily, may provide pleiotropic roles in the early and late stages of carcinogenesis. In particular, MIC-1 may contribute to the proliferation, migration, invasion, metastases, and treatment resistance of cancer cells as well as tumor-induced anorexia and weight loss in the late stages of cancer. Thus, secreted MIC-1 cytokine constitutes a new potential biomarker and therapeutic target of great clinical interest for the development of novel diagnostic and prognostic methods and/or cancer treatment against numerous metastatic, recurrent, and lethal cancers. PMID- 20578240 TI - PML down-regulation in soft tissue sarcomas. AB - To date, little is known concerning the promyelocytic leukemia gene (PML) status in tumors of different origin, and its expression has never been evaluated in soft tissue sarcoma. The aim of the present study is focused on the identification of differences in terms of PML protein expression between different types of soft tissue sarcoma and the corresponding normal surrounding tissue. PML protein expression has been assessed by immunohistochemistry in six different histologic types of soft tissue sarcoma (synovial sarcoma, myofibroblastic sarcoma, angiosarcoma, liposarcoma, pleomorphic sarcoma, and leiomyosarcoma) and in the corresponding normal surrounding tissue. PML resulted significantly down-regulated in synovial sarcoma and in myofibroblastic sarcoma specimens. Also in angiosarcoma samples a significative difference in PML expression in comparison with normal specimens has been detected. Interestingly PML protein detection showed a different pattern of expression in the three liposarcoma histology types compared with corresponding nontumoral tissues. In particular PML protein resulted significantly down-regulated in myxoid liposarcoma and in dedifferentiated liposarcoma. On the contrary no statistically significant difference was observed in pleomorphic liposarcoma compared to normal tissue specimens. Further investigations are needed to confirm these data and to assess the possible value of PML expression as a prognostic factor in these extremely aggressive diseases. PMID- 20578241 TI - Mutual interaction and reciprocal down-regulation between c-met and insulin receptor substrate-1. AB - The insulin receptor substrate-1 (IRS-1) and c-met, the receptor for the hepatocyte growth factor (HGF) co-immuno-precipitate from lysates treated with the respective antibodies. The interaction between IRS-1 and c-met requires a tyrosyl phosphorylated IRS-1 and results in reciprocal down-regulation. IRS-1 inhibits cell motility, while the activated c-met promotes it. These and other results suggest an explanation for reports in the literature indicating that c met levels are high and IRS-1 levels are low in human cancer metastases. PMID- 20578242 TI - N-terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals. AB - The serine/threonine kinase PAK4 is a Rho GTPases effector protein implicated in many critical biological processes, including regulation of cell morphology and motility, embryonic development, cell survival, response to infection, and oncogenic transformation. Consistently with its pro-oncogenic features, PAK4 was found to be overexpressed in many cancer cell lines and tissues, and to be necessary to promote activation of survival pathways. PAK4, like other Paks, is now considered a promising target for specific therapy. Little is known on its modes of regulation, molecular partners, and substrates. Because the N-terminal regulatory moiety plays important roles in PAK4 activity and functions, even independently of GTPase interactions, in this study we employed an affinity chromatography approach to identify N-terminal domain binding partners. Within this protein region we identified a novel interaction domain involved in association with ribonucleoprotein (RNP) complexes, suggesting PAK4 implications in translational regulation. Indeed, we found that active PAK4 can affect (cap independent) translation from specific IRES sequences in vivo, and that the N terminal domain is critical for this regulation. Further, we could establish that within the RNP interacting sequence PAK4 regulatory domain contains targeting elements that drive cytoplasmic localization and act as nuclear export signal. Functional implication of endogenous PAK4 protein, which was found in both cytoplasmic and nuclear fractions, in IRES-mediated translation further underlines the significance of the reported findings. Our data reveal novel means for PAK4 regulation of gene expression, and provide new elements to understand the molecular mechanisms that determine PAK4 cellular localization and functions. PMID- 20578243 TI - Cbl-b enhances Runx2 protein stability and augments osteocalcin promoter activity in osteoblastic cell lines. AB - Cbl-b is a member of Cbl family of E3 ubiquitin (Ub) ligase. Besides the important role in ubiquitination process, other members of Cbl family have been suggested to show non-ubiquitination-related function in regulation of osteoblastic differentiation. However, the role of Cbl-b in regulation of osteoblastic function has not been known yet. To elucidate the role of Cbl-b in regulation of osteoblastic function, we examined its effects on Runx2, a master gene of osteoblastic differentiation. We co-expressed Cbl-b and Runx2 in osteoblastic cell lines and tested their effects on osteocalcin promoter activity together with the expression of Runx2 and its downstream genes. Luciferase assay demonstrated that Cbl-b synergistically enhances osteocalcin promoter activity in conjunction with the effect on Runx2. Co-transfection of Cbl-b and Runx2 further upregulated Runx2 protein levels without any alteration in Runx2 mRNA expression. The upregulation of Runx2 protein by Cbl-b was inhibited by the treatment with lactacystin, a specific inhibitor of the 26S proteasome. These results indicated that Cbl-b would control Runx2 protein levels at the post-translational event. Moreover, the upregulation of downstream genes of Runx2 such as osteocalcin and alkaline phosphatase mRNA was also observed. These data propose the involvement of Cbl-b in the regulation of osteoblast-related genes expression. PMID- 20578244 TI - Role of Annexin A1 in mouse myoblast cell differentiation. AB - Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein involved in a broad range of cellular events. This study used molecular and microscopy approaches to explore the role of ANXA1 in mouse myoblast C2C12 cell differentiation. We report that ANXA1 expression increases during differentiation and that the down-regulation of ANXA1 significantly inhibits the differentiation process. ANXA1 is expressed in vivo in both quiescent and activated satellite cells and is highly localized in the cells that migrate in the lumen of regenerating fibers after an acute injury. Endogenous ANXA1 co-localizes with actin fibers at the protruding ends of undifferentiated but not differentiated cells suggesting a role of the protein in cell migration. Furthermore, ANXA1 neutralizing antibody reduces MyHC expression, decreases myotube formation and significantly inhibits cell migration. The data reported here suggest for the first time that ANXA1 plays a role in myogenic differentiation. PMID- 20578245 TI - Caenorhabditis elegans mitofilin homologs control the morphology of mitochondrial cristae and influence reproduction and physiology. AB - Human mitofilin is a mitochondrial protein that controls cristae formation. Here, we investigated the role of the Caenorhabditis elegans mitofilin homologs, IMMT-1 and -2, in reproduction, physiology, and mitochondrial cristae formation. Mutation of either immt-1 or immt-2 produced defects in germline development and egg-laying. These defects were exacerbated by the double mutation, which greatly reduced motility, increased levels of reactive oxygen species, decreased mitochondrial mass, and imparted resistance to oxidative stress. Cryo-electron microscopy and electron tomography revealed that each of the single mutations resulted in curved and stacked mitochondrial crista tubules as well as a reduced number of crista junctions. The immt-2 mutation was also associated with the presence of outer mitochondrial membrane pores, which were larger in the double mutant. IMMT-1 and IMMT-2 proteins were localized to the inner mitochondrial membrane, as seen by immunoelectron microscopy, and they behaved as oligomers or large complexes with F(1)F(0) ATP synthase in native polyacrylamide gel electrophoresis. These findings suggest that the two C. elegans mitofilin isoforms have non-overlapping functions in controlling mitochondrial cristae formation. PMID- 20578246 TI - Neurite outgrowth from PC12 cells by basic fibroblast growth factor (bFGF) is mediated by RhoA inactivation through p190RhoGAP and ARAP3. AB - The rat pheochromocytoma cell line PC12 has been widely used as a model to study neuronal differentiation. PC12 cells give rise to neurites in response to basic fibroblast growth factor (bFGF). However, it is unclear whether bFGF promotes neurite outgrowth by inducing RhoA inactivation, and a mechanism for RhoA inactivation in PC12 cells in response to bFGF has not been reported. Lysophosphatidic acid (LPA) treatment and the expression of constitutively active (CA)-RhoA (RhoA V14) impaired neurite formation in response to bFGF, while Tat-C3 exoenzyme and the expression of dominant negative (DN)-RhoA (RhoA N19) stimulated neurite outgrowth. GTP-bound RhoA levels were reduced in response to bFGF, which suggests that the inactivation of RhoA is essential to neurite outgrowth in response to bFGF. To investigate the mechanism of RhoA inactivation, this study examined the roles of p190RhoGAP and Rap-dependent RhoGAP (ARAP3). DN-p190RhoGAP prevented neurite outgrowth, while WT-p190RhoGAP and Src synergistically stimulated neurite outgrowth; these findings suggest that bFGF promotes the inactivation of RhoA and subsequent neurite outgrowth through p190RhoGAP and Src. Furthermore, DN-Rap1 and DN-ARAP3 reduced neurite formation in PC12 cells. These results suggest that RhoA is likely to be inactivated by p190RhoGAP and ARAP3 during neurite outgrowth in response to bFGF. PMID- 20578247 TI - Local regulation of human breast xenograft models. AB - Breast cancer studies implant human cancer cells under the renal capsule, subcutaneously, or orthotopically and often use estrogen supplementation and immune suppressants (etoposide) in xenograft mouse models. However, cell behavior is significantly impacted by signals from the local microenvironment. Therefore, we investigated how the combinatorial effect of the location of injection and procedural differences affected xenograft characteristics. Patient-derived breast cancer cells were injected into mouse abdominal or thoracic mammary glands +/- estrogen and/or etoposide pretreatment. Abdominal xenografts had increased tumor incidence and volume, and decreased latency (P < 0.001) compared to thoracic tumors. No statistically significant difference in tumor volume was found in abdominal xenografts treated +/- estrogen or etoposide; however, etoposide suppressed tumor volume in thoracic xenografts (P < 0.02). The combination of estrogen and etoposide significantly decreased tumor incidence in both sites. In addition, mice treated +/- estradiol were injected orthotopically or subcutaneously with well-characterized breast cancer cell lines (MCF7, ZR75-1, MDA MB-231, or MCF10Ca1h). Orthotopic injection increased tumor volume; growth varied with estrogen supplementation. Location also altered methylation status of several breast cancer-related gene promoters. Lastly, vascularization of orthotopic tumors was significantly enhanced compared to subcutaneous tumors. These data suggest that optimal xenograft success occurs with orthotopic abdominal injections and illustrate molecular details of the compelling influence of the local microenvironment on in vivo models. PMID- 20578248 TI - Ex vivo organ culture of adipose tissue for in situ mobilization of adipose derived stem cells and defining the stem cell niche. AB - In spite of the advances in the knowledge of adipose-derived stem cells (ASCs), in situ location of ASCs and the niche component of adipose tissue (AT) remain controversial due to the lack of an appropriate culture system. Here we describe a fibrin matrix-supported three-dimensional (3D) organ culture system for AT which sustains the ASC niche and allows for in situ mobilization and expansion of ASCs in vitro. AT fragments were completely encapsulated within the fibrin matrix and cultured under dynamic condition. The use of organ culture of AT resulted in a robust outgrowth and proliferation in the fibrin matrix. The outgrown cells were successfully recovered from fibrin by urokinase treatment. These outgrown cells fulfilled the criteria of mesenchymal stem cells, adherence to plastic, multilineage differentiation, and cell surface molecule expression. In vitro label retaining assay revealed that newly divided cells during the culture resided in interstitium between adipocytes and capillary endothelial cells. These interstitial stromal cells proliferated and outgrew into the fibrin matrix. Both in situ mobilized and outgrown cells expressed CD146 and alpha-smooth muscle actin (SMA), but no endothelial cell markers (CD31 and CD34). The structural integrity and spatial approximation of CD31(-)/CD34(-)/CD146(+)/SMA(+) interstitial stromal cells, adipocytes, and capillary endothelial cells were well preserved during in vitro culture. Our results suggest that ASCs are natively associated with the capillary wall and more specifically, belong to a subset of pericytes. Furthermore, organ culture of AT within a fibrin matrix-supported 3D environment can recapitulate the ASC niche in vitro. PMID- 20578249 TI - MED and PSACH COMP mutations affect chondrogenesis in chicken limb bud micromass cultures. AB - Mutations in cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We studied the effects of over-expression of wild type and mutant COMP on early stages of chondrogenesis in chicken limb bud micromass cultures. Cells were transduced with RCAS virus harboring wild type or mutant (C328R, PSACH; T585R, MED) COMP cDNAs and cultured for 3, 4, and 5 days. The effect of COMP constructs on chondrogenesis was assessed by analyzing mRNA and protein expression of several COMP binding partners. Cell viability was assayed, and evaluation of apoptosis was performed by monitoring caspase 3 processing. Over-expression of COMP, and especially expression of COMP mutants, had a profound affect on the expression of syndecan 3 and tenascin C, early markers of chondrogenesis. Over-expression of COMP did not affect levels of type II collagen or matrilin-3; however, there were increases in type IX collagen expression and sulfated proteoglycan synthesis, particularly at day 5 of harvest. In contrast to cells over-expressing COMP, cells with mutant COMP showed reduction in type IX collagen expression and increased matrilin 3 expression. Finally, reduction in cell viability, and increased activity of caspase 3, at days 4 and 5, were observed in cultures expressing either wild type or mutant COMP. MED, and PSACH mutations, despite displaying phenotypic differences, demonstrated only subtle differences in their cellular viability and mRNA and protein expression of components of the extracellular matrix, including those that interact with COMP. These results suggest that COMP mutations, by disrupting normal interactions between COMP and its binding partners, significantly affect chondrogenesis. PMID- 20578250 TI - The influence of attachment representation on parental perception and interpretation of infant emotions: A multilevel approach. AB - The aim of the study was to investigate parental perception and interpretation of infant emotional expression depending on their attachment representation. Forty six parents' responses to infant pictures depicting positive, neutral, and negative emotions were assessed on the level of affective judgments (valence, arousal), mimic responses (facial muscle activity), and of the eyelid reflex (using the startle paradigm). Results revealed small differences between parents of different attachment representations with respect to their subjective evaluations. However, secure parents, as compared to insecure ones, showed a positive bias in their mimic responses to infant pictures. The modulation of the startle response indicated a negative evaluation of negative infant emotion expressions in dismissing parents, while an augmentation of the startle response to negative infant emotions could not be observed in secure and preoccupied parents. The findings highlight the role of attachment experiences for emotional information processing in parents and its consequences for parental behavior. PMID- 20578251 TI - Doing what's right for the resuscitated. PMID- 20578252 TI - Buenos Aires to New Haven: a dream trip. PMID- 20578253 TI - Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice. AB - The innate immune response plays an essential role in the prevention of early viral dissemination. We used the lymphocytic choriomeningitis virus model system to analyze the role of tissue macrophages/Kupffer cells in this process. Our findings demonstrated that Kupffer cells are essential for the efficient capture of infectious virus and for preventing viral replication. The latter process involved activation of Kupffer cells by interferon (IFN)-I and prevented viral spread to neighboring hepatocytes. In the absence of Kupffer cells, hepatocytes were not able to suppress virus replication, even in the presence of IFN-I, leading to prolonged viral replication and severe T cell-dependent immunopathology. CONCLUSION: Tissue-resident macrophages play a crucial role in early viral capture and represent the major liver cell type exhibiting responsiveness to IFN-I and providing control of viral replication. PMID- 20578254 TI - Interleukin-28B genetic variants and hepatitis virus infection by different viral genotypes. AB - Genetic host factors may modify the course of the hepatitis C virus (HCV) infection. Very recently, a genome-wide scan that reported association of the IL28B locus with response to treatment in HCV infection was published. The aim of the current study was to investigate the relationship of this locus with outcome of HCV infection in a cohort constituted by a total of 731 Spanish individuals. From these, 284 were subjects with persistent infection, 69 were individuals who naturally cleared the virus, and 378 were noninfected subjects. Genotyping of the rs12979860 (C>T) in the IL28B locus was performed using a TaqMan 5' allelic discrimination assay. The CC genotype was overrepresented among patients infected with viral genotypes non-1 (66.7% versus 39.1% in patients infected with viral genotype-1, P = 8.5 x 10(-5), odds ratio [OR] = 0.32, 95% confidence interval [CI] 0.17-0.60); patients with spontaneous resolution of infection (72.5% versus 45.6% of the individuals with persistent infection, P = 6.2 x 10(-5), OR = 0.32; 95%CI, 0.18-0.57); and lastly, patients with sustained response (60.2% versus 32.1% found in patients with nonsustained response, P = 3.1 x 10(-5), OR = 0.31; 95%CI, 0.17-0.56). CONCLUSION: We have found different rates of viral genotype infection depending on the IL28B variant as well as an association of this locus with natural and treatment-mediated response. PMID- 20578255 TI - Changes in the relationship between nursing home financial performance and quality of care under public reporting. AB - The relationship between financial performance and quality of care in nursing homes is not well defined and prior work has been mixed. The recent focus on improving the quality of nursing homes through market-based incentives such as public reporting may have changed this relationship, as public reporting provides nursing homes with increased incentives to engage in quality-based competition. If quality improvement activities require substantial production costs, nursing home profitability may become a more important predictor of quality under public reporting. This study explores the relationship between financial performance and quality of care and test whether this relationship changes under public reporting. Using a 10-year (fiscal years 1997-2006) panel data set of 9444 skilled nursing facilities in the US, this study employs a facility fixed-effects with and without instrumental variables approach to test the effect of finances on quality improvement and correct for potential endogeneity. The results show that better financial performance, as reflected by the 1-year lagged total profit margin, is modestly associated with higher quality but only after public reporting is initiated. These findings have important policy implications as federal and state governments use market-based incentives to increase demand for high-quality care and induce providers to compete based on quality. PMID- 20578256 TI - Familial X;Y translocation with distinct phenotypic consequences: Characterization using FISH and array CGH. AB - X;Y translocation is a relatively rare event in humans. Analyzed cytogenetically, the majority of these aberrations have breakpoints at Xp22 and Yq11. Females with t(X;Y)(p22;q11) are phenotypically normal except for short stature, while the males may have abnormalities. Aberrations that lead to nullisomy of the deleted region and complete loss of the respective genes have been recognized as a cause of variable contiguous gene syndromes in males. The phenotype depends on the extent and position of the deletion showing the variable association of apparently unrelated clinical manifestations such as ichthyosis, chondrodysplasia punctata, hypogonadotropic hypogonadism with anosmia, ocular albinism, short stature, and mental retardation. In addition, some patients have been reported with symptoms of attention deficit hyperactivity disorder. The extent of terminal Xp deletions is limited by the presence of male lethal genes in Xp22.2 at about 10-11 Mb from the telomere. The deletions in the majority of viable reported male patients extend to the STS ( approximately 7.0 Mb) or to the KAL1 ( approximately 8.5 Mb) loci. We present a clinical, cytogenetic, FISH, and array CGH study of a family with an Xp;Yq translocation. The chromosomal status is also discussed in the light of their phenotypic traits. The final karyotypes of the patients were designated as: Patient 1: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(Xpter ,DXZ1+,Xqter+)mat.arr cgh Xp22.31p22.33(RP11-60P14 --> RP13-391G2)x0;arr cgh Yq11.221qter (RP11-235I1 --> RP11-270H4)x2.Patient 2: 46,X,der(X),t(X;Y)(p22;q12).ish der(X)(Xpter-,DXZ1+,Xqter+)mat.arr cgh Xp22.31p22.33(RP11-60P14 --> RP13-391G2)x1;arr cgh Yq11.221qter (RP11-235I1 --> RP11-270H4)x1. PMID- 20578257 TI - Hyperphosphatasia with seizures, neurologic deficit, and characteristic facial features: Five new patients with Mabry syndrome. AB - Persistent hyperphosphatasia associated with developmental delay and seizures was described in a single family by Mabry et al. 1970 (OMIM 239300), but the nosology of this condition has remained uncertain ever since. We report on five new patients (two siblings, one offspring of consanguineous parents, and two sporadic patients) that help delineate this distinctive disorder and provide evidence in favor of autosomal recessive inheritance. Common to all five new patients is facial dysmorphism, namely hypertelorism, a broad nasal bridge and a tented mouth. All patients have some degree of brachytelephalangy but the phalangeal shortening varies in position and degree. In all, there is a persistent elevation of alkaline phosphatase activity without any evidence for active bone or liver disease. The degree of hyperphosphatasia varies considerably ( approximately 1.3 20 times the upper age-adjusted reference limit) between patients, but is relatively constant over time. In the first family described by Mabry et al. 1970, at least one member was found to have intracellular inclusions on biopsy of some but not all tissues. This was confirmed in three of our patients, but the inclusions are not always observed and the intracellular storage material has not been identified. PMID- 20578258 TI - Down syndrome risk calculation for a twin fetus taking account of the nuchal translucency in the co-twin. AB - OBJECTIVE: The objective of this study was to describe and illustrate a method for calculating fetus-specific Down syndrome risk in twins, allowing for between fetus nuchal translucency (NT) correlation. METHODS: The between-fetus correlation coefficient of log NT, in multiples of the median, was estimated from a series of 325 unaffected twins after adjustment for sonographer bias. A bivariate log Gaussian model was used to calculate likelihood ratios for discordant and concordant Down syndrome. Applying these to the prior maternal age specific risk yielded risks in monozygous and dizygous twins. The weighted average risk was then computed with weights relating to chorionicity, gender, assisted reproduction and ethnicity. The method was illustrated using examples. RESULTS: The correlation coefficient in unaffected pregnancies was 0.45 (P < 0.0001) and estimated to be 0.12 and 0.04 in discordant and concordant twins, respectively. The examples showed very large differences in the risks obtained when the extent of correlation in NT between fetuses is taken into account and when the measurements are treated as independent. CONCLUSION: Fetus-specific Down syndrome risks in twins should be calculated using its own NT value as well as that of the co-twin. PMID- 20578259 TI - Prenatal diagnosis of trisomy 3 mosaicism in a fetus with severe IUGR. PMID- 20578260 TI - Overexpression of aspartyl-(asparaginyl)-beta-hydroxylase in hepatocellular carcinoma is associated with worse surgical outcome. AB - The association between the overexpression of aspartyl-(asparaginyl)-beta hydroxylase (AAH) and the invasiveness of hepatocellular carcinoma (HCC) in vitro has been reported. However, the prognostic value of AAH expression in HCC remains unclear. The purpose of this study was to investigate the relationship between AAH expression, tumor recurrence, and patient survival. We identified AAH as the most overexpressed gene in HCC by way of complementary DNA microarray hybridization. A prospective study of 233 patients undergoing curative resection indicated that AAH expression was an independent factor affecting recurrence (hazard ratio [HR] 3.161, 95% confidence interval [CI] 2.115-4.724, P < 0.001) and survival (HR 2.712, 95% CI 1.734-4.241, P < 0.001). Patients with AAH overexpression had a poorer prognosis than those with AAH underexpression (P < 0.001 for both recurrence and survival). In Barcelona Clinic Liver Cancer stage A patients with AAH overexpression or underexpression, the tumor recurrence and survival rates were also statistically different (45% and 85% versus16% and 33% in 1- and 3-year cumulative recurrence rates, respectively; 73% and 37% versus 90% and 80% in 1- and 3-year survival rates, respectively; P < 0.001 for both). Furthermore, in stage A patients with tumors measuring < or =5 cm in diameter, the time to recurrence was 26.7 +/- 1.6 versus 51.9 +/- 2.8 months, and the 1- and 3- year survival rates were 97% and 52% versus 100% and 90% in AAH overexpression and underexpression patients, respectively (P < 0.001 for both). CONCLUSION: AAH overexpression in HCC is strongly correlated with worse surgical outcome, and this molecule likely provides a more precise prognostic predictor in early stage HCCs. PMID- 20578261 TI - Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma. AB - Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n = 30) and benign diseases (n = 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity = 90.0%, specificity = 76.3%, and area under the curve = 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported. CONCLUSION: Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores. PMID- 20578262 TI - CD151 modulates expression of matrix metalloproteinase 9 and promotes neoangiogenesis and progression of hepatocellular carcinoma. AB - Tetraspanin CD151 is involved in several pathological activities associated with tumor progression, including neoangiogenesis. However, the role and molecular mechanism of CD151 in the neoangiogenesis of hepatocellular carcinoma (HCC) remain enigmatic. We found that the level of expression of matrix metalloproteinase 9 (MMP9) was positively associated with CD151 expression in HCC cells. We developed a zone-by-zone blockade and demonstrated that overexpression of CD151 in HCC cells facilitated MMP9 expression through a phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3beta (GSK 3beta)/Snail signaling pathway. In contrast, down-regulation of CD151 expression impaired the ability of HCC cells to form microvessels in vitro and reduced their in vivo metastatic potential. In a clinical setting, a significant correlation of the expression of CD151 with MMP9 expression and with microvessel density (MVD) was revealed by Pearson correlation analysis of HCC patients. The postoperative 3 , 5-, and 7-year overall survival rates of HCC patients with CD151(high)/MMP9(high)/MVD(high) were significantly lower than those of the CD151(low)/MMP9(low)/MVD(low) group or groups in which only one or two of CD151, MMP9, and MVD were highly expressed. Cumulative recurrence rates were also highest in HCC patients with CD151(high)/MMP9(high)/MVD(high) in comparison with the other groups. Multivariate Cox proportional hazards analysis showed that the concomitant overexpression of CD151, MMP9, and MVD was an independent marker for predicting poor prognosis of HCC. CONCLUSION: Overexpression of CD151 up regulated the expression of MMP9 through the PI3K/Akt/GSK-3beta/Snail pathway. CD151-dependent neoangiogenesis appeared to promote the progression of HCC, and this suggests that CD151 may be useful as a high-priority therapeutic target for antiangiogenesis in HCC. PMID- 20578263 TI - Knockout of secretin receptor reduces large cholangiocyte hyperplasia in mice with extrahepatic cholestasis induced by bile duct ligation. AB - During bile duct ligation (BDL), the growth of large cholangiocytes is regulated by the cyclic adenosine monophosphate (cAMP)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and is closely associated with increased secretin receptor (SR) expression. Although it has been suggested that SR modulates cholangiocyte growth, direct evidence for secretin-dependent proliferation is lacking. SR wild-type (WT) (SR(+/+)) or SR knockout (SR(-/-)) mice underwent sham surgery or BDL for 3 or 7 days. We evaluated SR expression, cholangiocyte proliferation, and apoptosis in liver sections and proliferating cell nuclear antigen (PCNA) protein expression and ERK1/2 phosphorylation in purified large cholangiocytes from WT and SR(-/-) BDL mice. Normal WT mice were treated with secretin (2.5 nmoles/kg/day by way of osmotic minipumps for 1 week), and biliary mass was evaluated. Small and large cholangiocytes were used to evaluate the in vitro effect of secretin (100 nM) on proliferation, protein kinase A (PKA) activity, and ERK1/2 phosphorylation. SR expression was also stably knocked down by short hairpin RNA, and basal and secretin-stimulated cAMP levels (a functional index of biliary growth) and proliferation were determined. SR was expressed by large cholangiocytes. Knockout of SR significantly decreased large cholangiocyte growth induced by BDL, which was associated with enhanced apoptosis. PCNA expression and ERK1/2 phosphorylation were decreased in large cholangiocytes from SR(-/-) BDL compared with WT BDL mice. In vivo administration of secretin to normal WT mice increased ductal mass. In vitro, secretin increased proliferation, PKA activity, and ERK1/2 phosphorylation of large cholangiocytes that was blocked by PKA and mitogen-activated protein kinase kinase inhibitors. Stable knockdown of SR expression reduced basal cholangiocyte proliferation. SR is an important trophic regulator sustaining biliary growth. CONCLUSION: The current study provides strong support for the potential use of secretin as a therapy for ductopenic liver diseases. PMID- 20578264 TI - Deletion of interleukin-6 in mice with the dominant negative form of transforming growth factor beta receptor II improves colitis but exacerbates autoimmune cholangitis. AB - The role of interleukin-6 (IL-6) in autoimmunity attracts attention because of the clinical usage of monoclonal antibodies to IL-6 receptor (IL-6R), designed to block IL-6 pathways. In autoimmune liver disease, activation of the hepatocyte IL 6/STAT3 (signal transducer and activator of transcription 3) pathway is associated with modulating pathology in acute liver failure, in liver regeneration, and in the murine model of concanavalin A-induced liver inflammation. We have reported that mice expressing a dominant negative form of transforming growth factor beta receptor II (dnTGFbetaRII) under control of the CD4 promoter develop both colitis and autoimmune cholangitis with elevated serum levels of IL-6. Based on this observation, we generated IL-6-deficient mice on a dnTGF-betaRII background (dnTGFbetaRII IL-6(-/-)) and examined for the presence of antimitochondrial antibodies, levels of cytokines, histopathology, and immunohistochemistry of liver and colon tissues. As expected, based on reports of the use of anti-IL-6R in inflammatory bowel disease, dnTGFbetaRII IL-6(-/-) mice manifest a dramatic improvement in their inflammatory bowel disease, including reduced diarrhea and significant reduction in intestinal lymphocytic infiltrates. Importantly, however, autoimmune cholangitis in dnTGFbetaRII IL-6(-/-) mice was significantly exacerbated, including elevated inflammatory cytokines, increased numbers of activated T cells, and worsening hepatic pathology. CONCLUSION: The data from these observations emphasize that there are distinct mechanisms involved in inducing pathology in inflammatory bowel disease compared to autoimmune cholangitis. These data also suggest that patients with inflammatory bowel disease may not be the best candidates for treatment with anti-IL-6R if they have accompanying autoimmune liver disease and emphasize caution for therapeutic use of anti-IL-6R antibody. PMID- 20578265 TI - Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: evidence for a gene-gene interaction. AB - Common genetic variants significantly influence complex diseases such as primary biliary cirrhosis (PBC). We recently reported an association between PBC and a single nucleotide polymorphism (rs231725) of the immunoreceptor gene cytotoxic T lymphocyte antigen 4 (CTLA4). We hypothesized that PBC risk attributed to this polymorphism might be increased by propensity to an overly robust inflammatory response. Thus, we examined its potential interaction with the commonly studied 308AG promoter polymorphism (rs1800629) of the tumor necrosis factor (TNF) gene for which the variant TNF2A allele causes increased TNF production. The polymorphisms were genotyped in 866 PBC patients and 761 controls from independent US and Canadian registries; the effects of individual single nucleotide polymorphisms (SNPs) and their interaction on PBC risk was assessed by logistic regression. The reported association of PBC with the CTLA4 "A/A" genotype was replicated in the Canadian cohort and significant for PBC risk in the combined data (odds ratio [OR], 1.68; P = 0.0005). TNF2A allele frequency was elevated in PBC patients, but only reached borderline significance using the combined data (OR, 1.21; P = 0.042). Analysis showed that TNF2A carriage was significantly increased in CTLA4 "A/A" PBC patients compared with CTLA4 "A/A" controls (39.7% versus 16.5%, P = 0.0004); no apparent increase of TNF2A carriage was noted in CTLA4 "A/G" or "G/G" individuals. Finally, interaction under a logistic model was highly significant, as TNF2A carriage in combination with the CTLA4 "A/A" genotype was present in 6.5% of PBC patients, compared with 1.7% of controls (OR, 3.98; P < 0.0001). CONCLUSION: TNF2A amplifies the CTLA4 rs231725 "A/A" genotype risk for PBC. Although the mechanisms remain unclear, the premise that deficiency in T-cell regulation resulting in an increased risk of PBC is amplified by overexpression of an important proinflammatory cytokine provides a basis for future functional studies. PMID- 20578266 TI - Fatty liver and fibrosis in glycine N-methyltransferase knockout mice is prevented by nicotinamide. AB - Deletion of glycine N-methyltransferase (GNMT), the main gene involved in liver S adenosylmethionine (SAM) catabolism, leads to the hepatic accumulation of this molecule and the development of fatty liver and fibrosis in mice. To demonstrate that the excess of hepatic SAM is the main agent contributing to liver disease in GNMT knockout (KO) mice, we treated 1.5-month-old GNMT-KO mice for 6 weeks with nicotinamide (NAM), a substrate of the enzyme NAM N-methyltransferase. NAM administration markedly reduced hepatic SAM content, prevented DNA hypermethylation, and normalized the expression of critical genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis. More importantly, NAM treatment prevented the development of fatty liver and fibrosis in GNMT-KO mice. Because GNMT expression is down-regulated in patients with cirrhosis, and because some subjects with GNMT mutations have spontaneous liver disease, the clinical implications of the present findings are obvious, at least with respect to these latter individuals. Because NAM has been used for many years to treat a broad spectrum of diseases (including pellagra and diabetes) without significant side effects, it should be considered in subjects with GNMT mutations. CONCLUSION: The findings of this study indicate that the anomalous accumulation of SAM in GNMT-KO mice can be corrected by NAM treatment leading to the normalization of the expression of many genes involved in fatty acid metabolism, oxidative stress, inflammation, cell proliferation, and apoptosis, as well as reversion of the appearance of the pathologic phenotype. PMID- 20578267 TI - Theophylline improves steroid sensitivity in acute alcoholic hepatitis. AB - Corticosteroid therapy has shown some benefit in severe acute alcoholic hepatitis (AAH); however, this is limited by uncertainty in patient selection and variable clinical response. Theophylline has been shown to ameliorate impaired steroid sensitivity in chronic obstructive pulmonary disease by facilitating corticosteroid-induced silencing of proinflammatory genes. We aimed to explore the mechanistic basis of the variable response to corticosteroid therapy seen in patients with AAH and to address the extent to which theophylline can improve this response. The ability of dexamethasone to inhibit phytohemagglutinin-induced lymphocyte proliferation was assessed by (3)H-thymidine incorporation in 12 severe AAH patients and age-matched and sex-matched controls. Steroid sensitivity was measured in terms of I(max), the maximum inhibition of proliferation. The effect of 10(-5) M theophylline and, in survivors, change in I(max) during recovery were observed. Lymphocyte steroid sensitivity was found to be significantly reduced in AAH compared with controls (I(max) 67[+/-4.5]% versus 95[+/-2.3]%, P = 0.0002) and correlated with clinical markers of steroid responsiveness. In survivors, I(max) increased in recovery. Theophylline 10(-5) M significantly increased lymphocyte steroid sensitivity (I(max) 86[+/-6.6]% versus 67[+/-5.0]%, P = 0.027). CONCLUSION: Acute alcoholic hepatitis is associated with significant lymphocyte steroid insensitivity, which improves in recovery and can be ameliorated ex vivo by theophylline. This offers potential to rationalize corticosteroid prescribing in AAH and, furthermore, justifies investigation of this novel role for an existing pharmacological agent in this common and frequently fatal condition. PMID- 20578268 TI - A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NAFLD carries a higher risk of cardio-metabolic and liver-related complications, the latter being confined to NASH and demanding specific treatment. We assessed the efficacy of proposed treatments for NAFLD/NASH by reviewing reports of randomized controlled trials (RCTs) on online databases and national and international meeting abstracts through January 2010. Primary outcome measure was histological improvement; secondary outcome was biochemical improvement; improvement in radiological steatosis was also evaluated. Two reviewers extracted articles using predefined quality indicators, independently and in duplicate. Main outcomes of randomized controlled trials (RCTs) were pooled using random-effects or fixed effects models. Publication bias was assessed by funnel plots. Forty-nine RCTs (30 in NASH) were included: 23 RCTs (22 in NASH, 1 in NAFLD) had post-treatment histology. Most RCTs were small and did not exceed 1-year duration. Weight loss, thiazolidinediones (especially pioglitazone), and antioxidants were most extensively evaluated. Weight loss was safe and dose-dependently improved histological disease activity in NASH, but more than 50% of patients failed to achieve target weight loss. Thiazolidinediones improved steatosis and inflammation but yielded significant weight gain. RCTs with antioxidants yielded conflicting results and were heterogeneous with respect to type and dose of drug, duration, implementation of lifestyle intervention. Among the other agents, pentoxifylline, telmisartan and L-carnitine improved liver histology in at least 1 RCT in NASH; polyunsaturated fatty acid (PUFA) ameliorated biochemical and radiological markers of NAFLD. Other approaches yielded negative results. CONCLUSION: Well-designed RCTs of adequate size and duration, with histological endpoints, are needed to assess long-term safety and efficacy of proposed treatments on patient-oriented clinical outcomes. PMID- 20578272 TI - Diet and prevention of Alzheimer disease. PMID- 20578273 TI - Proceedings Microscopy and Microanalysis 2008, Albuquerque, New Mexico, USA, August 3-7, 2008. PMID- 20578274 TI - Rifaximin treatment in hepatic encephalopathy. PMID- 20578275 TI - Rifaximin treatment in hepatic encephalopathy. PMID- 20578276 TI - Prevalence of diabetes among men and women in China. PMID- 20578277 TI - The ABIM and recertification. PMID- 20578278 TI - The ABIM and recertification. PMID- 20578279 TI - North-South Korea maternal health project to continue. PMID- 20578280 TI - Botswana reduces mother-to-child transmission of HIV. PMID- 20578281 TI - Difficulties hit Bolivia's programme for pregnant women. PMID- 20578282 TI - New laws could improve women's health in Pakistan. PMID- 20578283 TI - Ocular surface tolerability of prostaglandin analogs in patients with glaucoma or ocular hypertension. AB - PURPOSE: To compare the ocular surface tolerability of latanoprost 0.005% preserved with 0.02% benzalkonium chloride (BAK), bimatoprost 0.03% preserved with 0.005% BAK, and travoprost 0.004% preserved with the proprietary preservative system sofZia in patients previously treated with latanoprost. METHODS: This randomized, multicenter, investigator-masked, parallel-group study enrolled patients with open-angle glaucoma or ocular hypertension who had been on latanoprost monotherapy for at least 4 weeks. At baseline, patients were randomized to receive once-daily bimatoprost (n=35), latanoprost (n=38), or travoprost (n=33) monotherapy for 3 months. Follow-up visits were at week 1, month 1, and month 3. The primary outcome measure was physician-graded conjunctival hyperemia at month 3. Secondary outcome measures included corneal staining with fluorescein and tear breakup time (TBUT). RESULTS: There were no significant differences among the treatment groups in conjunctival hyperemia scores, corneal staining, or TBUT at the latanoprost-treated baseline or at any follow-up visit. Baseline mean (standard error of the mean) values were as follows--conjunctival hyperemia: bimatoprost 0.74 (0.10), latanoprost 0.74 (0.11), travoprost 0.86 (0.12), P=0.692; corneal staining: bimatoprost 0.59 (0.12), latanoprost 0.70 (0.13), travoprost 0.48 (0.11), P=0.423; TBUT (in seconds): bimatoprost 9.1 (1.0), latanoprost 8.6 (0.8), travoprost 7.9 (0.8), P=0.578. Month 3 values were as follows--conjunctival hyperemia: bimatoprost 0.80 (0.12), latanoprost 0.74 (0.10), travoprost 0.98 (0.13), P=0.340; corneal staining: bimatoprost 0.71 (0.78), latanoprost 0.47 (0.64), travoprost 0.36 (0.62), P=0.110; TBUT (in seconds): bimatoprost 9.7 (5.3), latanoprost 9.2 (5.3), travoprost 9.7 (6.3), P=0.909. CONCLUSIONS: There were no significant differences among bimatoprost (preserved with 0.005% BAK), latanoprost (preserved with 0.02% BAK), and travoprost (preserved with sofZia) in objective clinical measures of ocular tolerability, including physician-graded hyperemia, corneal staining, and TBUT after 3 months of treatment. Longer-term studies are needed to further evaluate the ocular surface tolerability of these prostaglandin analogs. PMID- 20578284 TI - Enhanced sorption of polycyclic aromatic hydrocarbons from aqueous solution by modified pine bark. AB - To enhance removal efficiency of natural sorbent with polycyclic aromatic hydrocarbons (PAHs), single-solute and bi-solute sorption of phenanthrene and pyrene onto raw and modified pine bark were investigated. Pine bark was modified using Soxhlet extraction, saponification and acid hydrolysis, yielding six bark fractions with different chemical compositions. Raw pine bark exhibited high affinities with PAHs, and sorption was dominated by partitioning. The relatively nonlinear sorption isotherms of modified bark were attributed to the specific interaction between sorbate and aromatic core of sorbent. Comparison with lipid and suberin, lignin was the most powerful sorption medium, but which was almost completely suppressed by coexisting polysaccharide. After consuming polysaccharide by acid hydrolysis, sorption of pine bark fractions was notably increased (4-17 folds); and sorption of pyrene just decreased 16-34% with phenanthrene as a competitor. These observations suggest that pine bark is of great potential for PAHs removal and can be significantly promoted by acid hydrolysis for environmental application. PMID- 20578285 TI - Guest editors' introduction: special section on volume graphics and point-based graphics. PMID- 20578286 TI - Potential odour emission measurement in organic fraction of municipal solid waste during anaerobic digestion: relationship with process and biological stability parameters. AB - The aim of the present study is to investigate the correlation between microbial activity, i.e., biological stability measured by aerobic (OD20 test) and anaerobic tests (ABP test), and odour emissions of organic fraction of municipal solid waste during anaerobic digestion in a full-scale treatment plant considering the three stages of the process (input, digested and post-digested waste). The results obtained indicated that the stabilization of the treated material reduces the odour impact measured by the olfactometric approach. Successive application of gas chromatography mass spectrometry (GC-MS) and electronic nose (EN) allowed the characterization of the different groups of volatile organic compounds (VOCs) responsible of odour impacts determining, also, their concentration. Principal component and partial least squares analyses applied to the EN and GC-MS data sets gave good regression for the OD20 vs the EN and OD20 vs the GC-MS data. Therefore, OD20 reduction could be used as an odour depletion indicator. PMID- 20578287 TI - Milling pretreatment of sugarcane bagasse and straw for enzymatic hydrolysis and ethanol fermentation. AB - The effectiveness of ball milling (BM) and wet disk milling (WDM) on treating sugarcane bagasse and straw were compared. Pretreated materials were characterized by wide angle X-ray diffraction analysis, particle-size distribution and scanning electron microscopy and the effectiveness of pretreatments was evaluated by enzymatic hydrolysis and fermentation. Glucose and xylose hydrolysis yields at optimum conditions for BM-treated bagasse and straw were 78.7% and 72.1% and 77.6% and 56.8%, respectively. Maximum glucose and xylose yields for bagasse and straw using WDM were 49.3% and 36.7% and 68.0% and 44.9%, respectively. BM improved the enzymatic hydrolysis by decreasing the crystallinity, while the defibrillation effect observed for WDM samples seems to have favored enzymatic conversion. Bagasse and straw BM hydrolysates were fermented by Saccharomyces cerevisiae strains. Ethanol yields from total fermentable sugars using a C6-fermenting strain reached 89.8% and 91.8% for bagasse and straw hydrolysates, respectively, and 82% and 78% when using a C6/C5 fermenting strain. PMID- 20578288 TI - Erratum to "Neutrophil-dominant psoriasis-like skin inflammation induced by epidermal-specific expression of Raf in mice" [J. Dermatol. Sci. 58 (2010) 28 35]. AB - BACKGROUND: Raf is one of the downstream effectors of Ras GTPases. The induction of Raf in the epidermis causes the proliferation of keratinocytes and epidermal hyperplasia. However, skin inflammation accompanying Ras-induced epidermal reactions has not been fully delineated. OBJECTIVE: The aim of this study was to characterize inflammatory reactions induced by epidermal-specific Raf expression and to elucidate its role in skin inflammation. METHODS: K14-Raf:ER transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant estrogen receptor (ER) ligand binding domain-Raf fusion gene was expressed under control of the keratin 14 promoter, were used to characterize inflammatory reactions induced by Raf expression in the epidermis. RESULTS: A single topical application of 4OHT induced the expression of phosphorylated extracellular signal-related kinase 1/2 and elicited neutrophil-dominant inflammatory infiltrates in the skin. The Raf expression also rapidly induced the production of several cytokines and chemokines, including VEGF and CXCL1, by keratinocytes and inmouse skin in vivo. Furthermore, CD4-positive cells from regional lymph nodes had the potential to differentiate into IFNg- and IL17-producing cells. Treatment with an anti-Gr-1 antibody diminished the Raf-induced cutaneous inflammation and partially reversed the epidermal hyperplasia and hyperkeratosis. CONCLUSION: Activation of the Raf signaling pathway is involved in the epidermal hyperplasia and the neutrophil dominant cutaneous inflammatory reactions which are characteristics of psoriasis. PMID- 20578289 TI - Application of response surface methodology and artificial neural networks for optimization of recombinant Oryza sativa non-symbiotic hemoglobin 1 production by Escherichia coli in medium containing byproduct glycerol. AB - Production of recombinant Oryza sativa non-symbiotic hemoglobin 1 (OsHb1) by Escherichia coli was maximized in shake-flask cultures in media containing tryptone, yeast extract, sodium chloride and byproduct glycerol from biodiesel production. Response surface methodology (RSM) and artificial neural networks (ANNs), followed by multiple response optimization through a desirability function were applied to evaluate the amount of OsHb1 produced. The results obtained by the application of ANNs were more reliable since better statistical parameters were obtained. The optimal conditions were (g L(-1)), tryptone, 42.69; yeast extract, 20.11; sodium chloride, 17.77; and byproduct glycerol, 0.33. A maximum recombinant protein concentration of 3.50 g L(-1) and a minimum biomass concentration of 18.48 g L(-1) were obtained under these conditions. Although the concentrations of tryptone, yeast extract and sodium chloride are relatively high, the increase in the yield with respect to biomass formed (Y(P/X)) overcomes this disadvantage. PMID- 20578290 TI - Heavy metal removal and crude bio-oil upgrading from Sedum plumbizincicola harvest using hydrothermal upgrading process. AB - The main aim of this study was to separate heavy metals and yield crude bio-oil from a heavy metals hyperaccumulator harvest, Sedum plumbizincicola, through hydrothermal upgrading process. Parameters such as granularity, temperature, pressure, and duration were examined for their effect on the removal efficiency of heavy metals and upgrading efficacy of crude bio-oil. Maximum heavy metal removal efficiency of >99% and crude bio-oil upgrading efficiency of >63% were attained with an 18 mesh (1 mm) granularity, and 22.1 MPa at 370 degrees C in the presence of 10 mg/L additives for 60 s. Under these optimized conditions, an oil phase (mostly composed of phenolic hydrocarbons and derivatives), a water phase raffinate containing Zn2+ (0.39 g/L), Pb2+ (0.10 g/L), Cu2+ (0.16 g/L), and a solid phase (the hydrothermal upgrading residue, which completely satisfies the limit set by China legislation related to biosolids disposal, were obtained). PMID- 20578291 TI - Pathology quiz case 1: ameloblastic carcinoma. PMID- 20578292 TI - Pathology quiz case 2: extramedullary plasmacytoma (EMP). PMID- 20578293 TI - Rallying for ratios. Nurse-patient ratios lead to strike, testy negotiations. PMID- 20578294 TI - Hurdle for rate hikes. New York joins others in regulating premiums. PMID- 20578295 TI - Tough to define. NCQA to revise standards for medical homes. PMID- 20578296 TI - Creating a one-stop shop? Allscripts-Eclipsys deal would combine ambulatory, hospital EHR developers. PMID- 20578297 TI - Data we can believe in. It's an exciting time for backers of health IT, but we can't let our guard down. PMID- 20578298 TI - Leaders with the IT factor. Sentara's Bernd, Banner's Fine tapped in eighth annual competition. PMID- 20578299 TI - Before they were famous. Sentara's Bernd started thinking about EHRs as far back as 1992. PMID- 20578300 TI - Looking at the big picture. Banner Health's Fine set the course for standardized, systemwide IT rollout. PMID- 20578301 TI - Ground this pilot. Cover PBTs in LEED for healthcare, not a side program. PMID- 20578302 TI - Richer than ever in data. Foreword. PMID- 20578303 TI - Looking ahead. What the directors say.... PMID- 20578304 TI - Information technology. Too much to handle? PMID- 20578305 TI - Collaboration. A good connection. PMID- 20578306 TI - Intelligence. The right tools for the job. PMID- 20578307 TI - Patient care. Hospitals address health illiteracy for improved care, cost savings. PMID- 20578308 TI - The future of care. Part II: The continuum of care. PMID- 20578309 TI - Policy. 20 questions the coalition must nail if its agenda is to succeed. PMID- 20578310 TI - New government. Thousands of jobs at risk as SHAs face 2012 axe. PMID- 20578311 TI - Estates. Will building plans stay on the drawing board? PMID- 20578312 TI - On the new value for money. PMID- 20578313 TI - Do we need to be hearing this? PMID- 20578314 TI - Risk. The values of the virtual viewpoint. PMID- 20578315 TI - Patient safety. Taking a firm stand on falls prevention. PMID- 20578316 TI - Texas test. PHA, doc hospital sue over reform ownership rules. PMID- 20578317 TI - Bundle of problems. Hospitals seek to keep '72-hour rule' intact. PMID- 20578319 TI - Business-minded. Nominees sought for Physician Entrepreneur of the Year Award. PMID- 20578318 TI - Joining hands. Catholic hospital, health center partner. PMID- 20578320 TI - Big dividends. Annual survey of hospital systems shows a strong financial comeback thanks in large part to resurgent investment portfolios. PMID- 20578321 TI - Largest healthcare outsourcing companies. Ranked by total healthcare clients, 2008. PMID- 20578322 TI - [The operative treatment of the degenerative rupture of the anterior tibialis tendon]. AB - AIM: A degenerative tear of the anterior tibial tendon is a rare event compared to other tendons. The purpose of this study was to evaluate the functional results after surgical refixation. METHOD: In a retrospective study, we report the functional outcome of five consecutive operatively treated patients suffering from a tear close to the insertion site of the anterior tibial tendon. All patients were assessed postoperatively, the AOFAS and Richter scores were obtained and the range of motion in the ankle joint was evaluated. RESULTS: Preoperatively all patients presented with a significant walking impairment due to a reduced active dorsiflexion, so the decision for surgical refixation was made. In all cases an MRI scan was performed preoperatively. Postoperative immobilisation without weight-bearing was done for six weeks. All patients returned to their former activity level, were satisfied with the postoperative result and had a normal gait in the follow-up examination. The range of motion was equal on both sides, the median AOFAS score was 86 and the median Richter score was 90 out of 100. There were no postoperative complications. DISCUSSION: Untreated tears of the anterior tibial tendon lead to significant impairment of the ankle joint and deformities of the foot. There is no consensus about the treatment with recommendations for operative and non-operative treatment. Various surgical procedures have been described. The surgical reconstruction of the tendon leads to a restored function of the ankle joint and allows a normal gait and is therefore desirable. Due to the loss of function and the good results after surgical treatment in our study, the non-operative treatment is not advisable. CONCLUSION: Surgical repair of degenerative tears of the anterior tibial tendon leads to very good functional results and high patient satisfaction. PMID- 20578323 TI - [Proximal humeral fracture]. AB - Fractures of the proximal humerus are very common in elderly people with an increasing incidence. Complex fracture-patterns are observed. For radiological examination x-rays in 2 planes are mandatory. Often an additive CT-scan can be useful for a better understanding of the whole fracture-character. Limits of accepted fracture displacement decrease and reconstructive surgery is induced more frequently. Advantageous are the functional after-treatment and the early reintegration to the activities of daily living after osteosyntheses. Locking nail- and platesystems are competing standard-implants, whereas plate osteosynthesis is preferred in higher-part-fractures. Non-reconstructable fractures should be treated with a primary head replacement, in the form of a reverse prosthesis in patients older than 75 years. PMID- 20578324 TI - Health tips. Maintaining a support network. PMID- 20578325 TI - Reducing the risk of delirium after major surgery. PMID- 20578326 TI - Vulvar cancer. Skin changes not to be ignored. PMID- 20578327 TI - Hammertoe. Correcting a painful problem. PMID- 20578328 TI - Over the last several years, I've had several small spots of skin on my shoulder cut out due to skin cancer concerns. Now, my doctor say I have precancerous areas on my face that need treatment, but he's recommending I use a cream. Is that likely to work? PMID- 20578329 TI - Gendered space: a new look at Turkish modernisation. PMID- 20578330 TI - Paradoxes of gender: writing history in post-Communist Russia 1987-1998. PMID- 20578331 TI - Conceptualising gender in a Swedish context. PMID- 20578332 TI - Comparative effectiveness research: challenges for medical journals. PMID- 20578333 TI - [In memory of Prof. Dr. George Emil Palade (1912-2008)]. PMID- 20578334 TI - Keeping health insurance after a job loss: COBRA continuation coverage and subsidies. AB - Many Americans under 65 have health insurance through an employer. Beginning in 1985, a federal law known as COBRA required that eligible workers and their dependents have the option to continue employer-based group health coverage when employment is terminated. Because premiums for COBRA coverage can be very expensive, the 111th Congress included provisions in the American Recovery and Reinvestment Act of 2009 (and subsequent legislation) to temporarily subsidize premiums for those who have lost their jobs since September 2008. This issue brief outlines the eligibility rules for COBRA as well as the current COBRA subsidies. It also discusses the possible choices consumers may face between COBRA and individual insurance with the implementation of insurance market reforms in the Patient Protection and Affordable Care Act. PMID- 20578335 TI - Treating toenail fungus. PMID- 20578336 TI - Alert: protein drinks. You don't need the extra protein or the heavy metals our tests found. PMID- 20578337 TI - Depression & anxiety: readers reveal the therapists and drugs that helped. PMID- 20578339 TI - Scientific communication. PMID- 20578338 TI - [Arterial and venous thrombosis by eptacog alpha. Review of the literature about one case]. PMID- 20578340 TI - Rats: an old model made new. PMID- 20578342 TI - Out of Flatworld. PMID- 20578341 TI - Banking on (pluri) potential. PMID- 20578343 TI - Brave pioneers or clinical cowboys? PMID- 20578344 TI - Elaine Fuchs: ISSCR's president-elect. PMID- 20578345 TI - [Clinical and neuro-physiopathological effects of an olanzapine overdose]. PMID- 20578346 TI - [Acute cholestatic hepatitis probably due to fenofibrate]. PMID- 20578347 TI - The meaning behind the noise. PMID- 20578348 TI - Transcriptomics: individuality in the cellular world. PMID- 20578349 TI - Marine metagenomics. PMID- 20578350 TI - [Fedor Vasil'evich Sudzilovskii--a scientist, a teacher, and a public figure]. PMID- 20578351 TI - [Diagnosis and treatment of thyroid diseases--the current status and an overview]. PMID- 20578353 TI - [The use and problems of diagnostic guidelines for thyroid diseases]. PMID- 20578352 TI - [The frequency and status of latent thyroid dysfunctions in local residents]. PMID- 20578354 TI - [Recent progress in thyroid examinations--on anti-TSH receptor antibodies]. PMID- 20578355 TI - [Diagnostic approach: 1. Latent thyroid dysfunctions]. PMID- 20578356 TI - [Diagnostic approach to thyroid diseases. 2. Pitfalls in distinguishing non thyroidal illness (NTI)]. PMID- 20578357 TI - [Diagnostic approach to thyroid diseases. 3. Central hypothyroidism]. PMID- 20578358 TI - [Diagnostic approach to thyroid diseases. 4. Progress in ultrasonography of the thyroid and its application]. PMID- 20578359 TI - [Therapeutic guidelines--the current status and problems. 1. Chemotherapy of Basedow's disease]. PMID- 20578360 TI - [Therapeutic guidelines:progress in diagnosis and treatment. 2. Internal 131-I therapy of Basedow's disease]. PMID- 20578361 TI - [Therapeutic guidelines--the current status and problems. 3. Management of thyroid cancer]. PMID- 20578362 TI - [Therapy-resistant thyroid diseases. 1.Graves' ophthalmopathy]. PMID- 20578363 TI - [Therapy-resistant thyroid diseases. 2. Thyrotoxic crises]. PMID- 20578364 TI - [Therapy-resistant thyroid diseases. 3. Myxedema coma]. PMID- 20578365 TI - [Drug-induced thyroid diseases]. PMID- 20578366 TI - [Radiation exposure and development of thyroid cancer]. PMID- 20578367 TI - [How to discover and treat thyroid diseases: Discussion]. PMID- 20578368 TI - [Discovery of EML4-ALK, a new gene responsible for lung cancer, and the development of molecular targeted therapy]. PMID- 20578369 TI - [Frontier of chemotherapy of pancreatic cancer]. PMID- 20578370 TI - [Transient consciousness disturbance and syncope]. PMID- 20578371 TI - [Diagnosis through visual evidences: variant angina]. PMID- 20578372 TI - [Tests for type I hypersensitivity]. PMID- 20578373 TI - [Clinical quiz: a 67-year-old man with a hearing disorder and vertigo at the onset followed by progressive forgetfulness]. PMID- 20578374 TI - [Basis of professionalism: implementation of postgraduate ethics education for clinical practitioners]. PMID- 20578375 TI - A potential comprehensive role for highly concentrated platelet rich plasma (hcPRP) in bone regeneration. Criteria for successful bone grafting and advantages of grafting with hcPRP. PMID- 20578376 TI - Case Presentation: the blue line. PMID- 20578378 TI - [Study on electroacupuncture improving the single-foot supporting phase rate of stroke patients]. AB - OBJECTIVE: To provide biomechanics basis for acupuncture improving motor function of stroke patients. METHODS: With randomized controlled trial method, 21 cases were randomly divided into a control group (n = 10) and an acupuncture group (n = 10). The control group was only treated with basic neurology therapies, and acupuncture at Shenshu (BL 23), Qihaishu (BL 24), Dachangshu (BL 25) and Pishu (BL 20) etc. were added in the acu-puncture group. After treatment for 2 weeks, the scores of Fugl-Meyer (lower limb part) and Barthel Index assessment before and after treatment were compared, and the changes of the single-foot supporting phase rate were observed. RESULTS: After treatment, the scores of Fugl-Meyer (lower limb part) and Barthel Index assessment had no significant difference in the two groups as compared with those before treatment (P > 0.05), and the single foot supporting phase rate in acupuncture group had very significant improvement as compared with both those before treatment and those in the control group (P < 0.05 and P < 0.01, respectively). CONCLUSION: Acupuncture can increase the single foot supporting phase rate of stroke patients and the biomechanics assessment is more sensitive than the rehabilitation scale assessment. PMID- 20578377 TI - [Effects of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke: a randomized and controlled study]. AB - OBJECTIVE: To verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke. METHODS: Eighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment. RESULTS: The effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05). CONCLUSION: There is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training. PMID- 20578379 TI - [Controlled study on therapeutic effect of vessel pricking therapy and western medication for treatment of Henoch-Schonlein purpura nephritis]. AB - OBJECTIVE: To compare the difference of therapeutic effects between vessel pricking therapy and Prednisone for treatment of Henoch-Schonlein purpura nephritis. METHODS: Seventy cases of acute purpura nephritis syndrome were randomly divided into an observation group (40 cases) and a control group (30 cases). Patients in observation group were differentiated into sthenia and asthenia syndromes. Vessel pricking therapy was applied at Hegu (LI 4), Quchi (LI 11), Xuehai (SP 10) etc. by triangular needle for sthenia symptom; shallow needling was used at Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36) etc. by filiform needle. The control group was treated with oral admi-nidtration of Prednisone. The symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment of both groups were observed before and after treatment and therapeutic effects were compared. RESULTS: The total effective rate of 92.5% (37/40) in observation group was superior to that of 80.0% (24/30) in control group, and there was a significant difference between two groups (P < 0.05); the symptom score of TCM, 24 h urinary protein, red blood cell count of urinary sediment were all improved in both groups after treatment (all P < 0.05), and moreover, the improvement in observation group was superior to that of control group (all P < 0.05); after treatment, the symptom score of TCM of sthenia syndrome was lower than that of asthenia syndrome in observation group (P < 0.05). CONCLUSION: Vessel pricking therapy has a significant therapeutic effect for treatment of Henoch-Schonlein purpura nephritis, superior to that of oral administration of Prednisone, and the therapeutic effect is better for treating sthenia syndrome than for asthenia syndrome. PMID- 20578380 TI - [Efficacy observation of primary dysmenorrhea treated with isolated-herbal moxibustion on Shenque (CV 8)]. AB - OBJECTIVE: To observe the clinical efficacy on primary dysmenorrhea treated with isolated herbal moxibustion on Shenque (CV 8). METHODS: One hundred and two cases were randomized into isolated herbal moxibustion group and western medication group, 51 cases in each one. In isolated herbal moxibustion group, the cases were treated with isolated herbal moxibustion on Shenque (CV 8), and in western medication group, analgesic was administered. RESULTS: In isolated herbal moxibustion group, 17 cases were cured, 21 cases effective markedly, 9 cases effective and 4 cases failed. The total effective rate was 92.2%. In western medication group, 7 cases were cured, 11 cases effective markedly, 21 cases effective and 12 cases failed. The total effective rate was 76.5%. The comparison of the total effective rates between two groups indicated significant difference in statistics (P < 0.01), in which, the result in isolated herbal moxibustion group was superior to that in western medication group. In comparison of dysmenorrhea score before and after treatment and side effects of two groups, the significant differences presented in statistics, in which, the results in isolated herbal moxibustion group were superior to those in western medication group (all P < 0.01). CONCLUSION: The isolated herbal moxibustion on Shenque (CV 8) is superior to oral medication of analgesic for primary dysmenorrhea and it deserves to be promoted due to its advantages on safety, less side effect and good compliance of patients. PMID- 20578381 TI - [Clinical randomized controlled study on acupuncture for treatment of peripheral neuropathy induced by chemotherapeutic drugs]. AB - OBJECTIVE: To seek the effective treatment for peripheral neuropathy induced by chemotherapeutic drugs. METHODS: Sixty-four cases of peripheral neuropathy induced by Paclitaxel or Oxaliplatin were randomly divided into an acupuncture group and a medication group, 32 cases in each group. The acupuncture group was treated with therapeutic principle of dredging meridians and collaterals, tonifying qi and eliminating blood stasis, supplementing liver and kidney, nourishing blood and tendon. Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36), Qihai (CV 6) and Quchi (LI 11) etc. were selected. The medication group was treated with intramuscular injection of Cobamamide. The neurotoxicity of two groups was compared with questionnaire of peripheral neuropathy induced by chemotherapeutic drugs before and after treatment. RESULTS: The total effective rate for sensory nerve disorder of acupuncture group was 66.7% (20/30), which was superior to that of 40.0% (12/30) in medication group (P < 0.05). CONCLUSION: Acupuncture is more effective than Cobamamide for treatment of peripheral neuropathy induced by chemotherapeutic drugs, especially for moderate and severe sensory nerve disorder induced by paclitaxel. PMID- 20578382 TI - [Clinical observation on the principle of "single usage of acupoints of Shaoyang meridian" for treatment of facial paralysis in acute stage]. AB - OBJECTIVE: To compare different therapeutic effects between single usage of acupoints of Shaoyang meridian and the routine ones for treatment of Bell palsy in acute stage. METHODS: One hundred and twenty cases with Bell palsy during the first three days were random divided into an observation group and a control group, 60 cases in each group. In observation group, acupoints of Shaoyang meridians were used from the 3rd day till the 14th day, Fengchi (GB 20), Yifeng (TE 17), Wangu (GB 12) at the affected side etc. were selected, after the 15th day, the routine acupoints were applied, Hegu (LI 4) on both sides, Fengchi (GB 20), Quchi (LI 11), Yangbai (GB 14) at the affected side etc. were selected; the control group were treated with the same acupoints as the routine ones in observation group since the 3rd day. And both two groups were treated with oral administration of Prednisone. House-Brackmann (H-B) functional grading of facial nerve on the 3rd day with the one of the 60th day as well as electroneurography (ENoG) on the 3rd day with the one of the 14th day were compared respectively. RESULTS: The H-B grading improvement and cured rate were 95.0% (57/60) in observation group, which were suprior to 83.3% (50/60) in control group; the cured time in observation group was (34.21 +/- 8.026) days, significantly shorter than (42.78 +/- 9.029) days in control group (P < 0.05). CONCLUSION: On the basis of oral administration of Prednisone, single usage of acupoints of Shaoyang meridian in acute stage can make great improvement for recovery of Bell palsy, better than routine point selection. PMID- 20578383 TI - [Clinical observation on continuous electroacupuncture at Neiguan (PC 6) for arousing consciousness of comatose patients with severe craniocerebral trauma]. AB - OBJECTIVE: To observe the therapeutic effect of continuous electroacupuncture at Neiguan (PC 6) on the basis of routine treatment of western medicine for arousing consciousness of comatose patinents with severe craniocerebral trauma. METHODS: Fifty-six cases of severe cranio cerebral trauma patients whose scores of Glasgow Coma Scale (GCS) lower than 8 were randomly divided into an observation group (29 cases) and a control group (27 cases). Both groups were treated with routine western medicine. The observation group were additionally treated with continuous electroacupuncture at Neiguan (PC 6) as the main point. Arousal rate and time after one month and three months of two groups were observed, arousal rate and the total therapeutic effect of recovery of the patients with different types after three months were compared between two groups. RESULTS: The arousal time of the observation group was (18.57 +/- 7.14) days and the arousal rate was 72.4% (21/29) after one month, while (24.60 +/- 5.00) days and 37.0% (10/27) in control group, respectively. They were suprior in observation group to those in control group (P < 0.01, P < 0.05); the arousal time was (25.04 +/- 16.68) days in the observation group after three months of treatment, also shorter than (37.90 +/- 16.94) days in control group (P < 0.05). The arousal rate of patients with diffuse axonal injury was significantly higher than that of patients with non diffuse axonal injury in the observation group and patients with the same type in control group after one month (P < 0.05). The cured-markedly effective rate of 72.4% (21/29) in observation group was significantly higher than that of 37.0% (10/27) in control group (P < 0.05). CONCLUSION: The therapy of continunous electroacupuncture at Neiguan (PC 6) on the basis of routine western medicine has a better therapeutic effect for comatose patients with severe cranio cerebral trauma, especially for those with diffuse axonal injury. PMID- 20578384 TI - [Observation on therapeutic effect of tic disorders treated with local acupuncture]. AB - OBJECTIVE: To observe the clinical efficacy on tic disorders (TD) treated with local acupuncture. METHODS: The entire data of 196 cases, of which, 114 cases in acupuncture group were treated mainly with local acupuncture and 82 cases in western medication group were taken Tiapride tablets orally. YGTSS method was adopted for scoring and assessing the clinical efficacy. RESULTS: The apparent improvement was achieved in YGTSS motor tic score in two groups. The markedly effective rates were 90.4% and 84.2% in acupuncture group and western medication group, respectively (P < 0.05), without significant difference in statistics. The effective rates of transient tic disorder (TTD) in acupuncture group and western medication group were 100.0% and 83.3%, respectively (P < 0.05), which indicated that the efficacy of acupuncture on TTD was advantageous to medical therapy. The effective rates of three kinds of TD in acupuncture group were 100.0%, 88.2% and 84.2% separately, of which, the efficacy of acupuncture on TTD was advantageous as compared with that on chronic tic disorder (CTD) and Toureett's syndrome (TS) (P < 0.05). CONCLUSION: The overall efficacy on TD is similar between acupuncture and medical therapy, but the clinical efficacy of acupuncture on TTD is superior to medical therapy. Meanwhile, the efficacy of acupuncture on TTD is advantageous to that on CTD and TS. Hence, the intervention at early time can achieve satisfactory efficacy and probably prevent from CTD or TS. PMID- 20578385 TI - [Acupuncture for the lower extremity spasm induced by spinal injury: random controlled trial of single case]. AB - OBJECTIVE: To study whether acupuncture on the acupoints of the affected extremities was effective or not on the lower extremity spasm in spinal injury, and observe the tolerance of patients to acupuncture. METHODS: The random controlled trial of single case was adopted among 9 patients. The heavy manipulation and gentle manipulation of acupuncture on the lower extremities, physical therapy as well as corresponding control therapy (acupuncture or other therapy on the upper extremities) were applied to each case separately for 3 cycles of treatment, totally for 29 weeks of treatments. The therapeutic effective outcomes were determined according to the index of clinical spasm, daily spasm frequency and the patient reported outcome. RESULTS: None of the three therapies made the index of clinical spasm worse in 9 patients (all P > 0.05), and there was no significant statistical difference in comparison among three therapies (P > 0.05). Concerning to the improvement in daily spasm frequency, the result of heavy manipulation therapy was inferior apparently to the other two therapies (P < 0.05). The outcome report indicated that the patients were unwilling to accept the stimulation induced by heavy manipulation. CONCLUSION: The spasm induced by spinal injury can not be aggravated in tendency by acupuncture on the affected extremities. Thus, acupuncture is a kind of safe therapy for spasm. But the heavy manipulation of acupuncture may be the factor to impact the patient for the option of acupuncture treatment. PMID- 20578386 TI - [Observation on therapeutic effect of dry eye syndrome treated with acupuncture on the acupoints around the eyes]. AB - OBJECTIVE: To observed the clinical efficacy on dry eye syndrome treated with acupuncture on the acupoints around the eyes. METHODS: Fifty-six cases of dry eye syndrome were divided into two groups, acupuncture group and western medicine group, 28 cases in each one. In acupuncture group, acupuncture was applied to Jingming (BL 1), Cuanzhu (BL 2), Sizhukong (TE 23), Tongziliao (GB 1), etc. In western medicine group, the topical artificial tear eye drops were administered. The corneal fluorescein staining, breaking-up time (BUT), tear volume and the symptom score were observed before and after treatment in two groups. RESULTS: In comparison before and after treatment in acupuncture group, the statistical significant difference presented in BUT, tear volume and the symptom score (all P < 0.01). In comparison before and after treatment in western medicine group, the statistical significant difference presented in corneal staining, BUT and the symptom score (P < 0.01). The improvements in BUT, tear volume and the symptom score in acupuncture group were superior to those in western medicine group (P < 0.01). CONCLUSION: Acupuncture on the acupoints around the eyes achieves a quite good efficacy on dry eye syndrome. PMID- 20578387 TI - [Analysis of information detection of biological energy on Shangjuxu (ST 37) with acupuncture]. AB - OBJECTIVE: To study the impact of Shangjuxu (ST 37) with acupuncture on each zang fu organ in human body so as to provide the objective evidence of the efficacy induced by acupuncture on gastrointestinal system and other organs. METHODS: Shangjuxu (ST 37) was punctured bilaterally. The biological energy information medical diagnosis apparatus was applied to observe the changes in the energy in every part of human body before acupuncture and 10 min, 1 h and 24 h after acupuncture separately. RESULTS: Acupuncture on this point not only adjusted the digestive functions in esophagus, stomach, rectum and other parts, but also affected the functions of other organs, such as lung, uterus/prostate gland, thymus and spines, resulting in either rising or falling of the energy. The maximal peak value of the change happened 1 h after acupuncture. CONCLUSION: (1) Shangjuxu (ST 37) works mainly on rectum in the adjustment of large intestine functions and induces quite large impacts also on the energy changes of esophagus and stomach. (2) The energy changes in other organs, such as thymus, lung, reproductive organ and spine reveal that the actual indications of ST 37 may exceed to the currently-recognized range. (3) The peak value of the effect produced by acupuncture presents in 1 h after needling. PMID- 20578388 TI - [Effect on body surface thermograph in patients with myofascial pain syndrome treated with moxibustion on Yanglingquan (GB 34) ]. AB - OBJECTIVE: To compare the immediate effect of moxibustion on Yanglingquan (GB 34) on body surface thermograph between the patients with myofascial pain syndrome (MPS) and healthy people. METHODS: Thirty-five cases of MPS were selected in observation group and 15 cases of healthy people were in control group. ATIR-M301 medical infrared imaging device was used to observe the changes in body surface thermograph before and 15 min after moxibustion on Yanglingquan (GB 34) The qualitative analysis of picture pattern and the quantitative analysis of temperature were integrated to compare the differences between two groups. RESULTS: Concerning to the infrared thermograph expression on the back of MPS cases in observation group, the abnormal thermal zone presented in 88.6% of the cases, mostly distributed in the upper and secondly in the lower back. The spinal thermal line was broken or disappeared ine about 50% of cases. The location of pain complained by 71.4% of cases was coincident with the zone of infrared thermograph expression. There was statistical significant difference in the temperatures difference of the two sides in the upper abnormal thermal zone on the back in observation group as compared with control group (P < 0.001). Body surface thermograph on the back were impacted by moxibustion on Yanglingquan (GB 34) for either MPS patients or healthy people, especially in upper back and rhomboid fossa. Moxibustion on Yanglingquan (GB 34) increased much more apparently the temperature on the upper back in MPS patients as compared with healthy people (P < 0.05). CONCLUSION: Moxibustion on Yanglingquan (GB34) brings the immediate improvements in the back thermograph for MPS patients. PMID- 20578389 TI - [Comparative study on the analgesic effect of electroacupuncture at "Sanyinjiao" (SP 6), "Hegu" (LI 4) and "Xuehai" (SP 10) in dysmenorrhea rats]. AB - OBJECTIVE: To observe and compare the analgesic effect of electroacupuncture (EA) at "Sanyinjiso" (SP 6), "Hegu" (LI 4) and "Xuehai" (SP 10) in dysmenorrhea rats so as to investigate the functional specificity of acupoint. METHODS: One hundred SD female rats aged three-month-old in the diestrus examined by the vaginal smear screening were randomly divided into a saline group, a model group, a Sanyinjiao (SF 6) group, a Hegu (LI 4) group and a Xuehai (SF 10) group, 20 rats in each group. The rats in the last four groups were given Estradiol Benzoate combined with Oxytocin to prepare the models of dysmenorrhea and in the saline group were given the same dose of saline. Last three groups were treated with electroacupuncture (EA) at Sanyinjiao" (SF 6), "Hegu" (LI 4) and 'Xuehai" (SF 10) respectively. The writhing behaviors of the rats in each group were observed within 20 min performing electroacupuncture from the start of the pain and the waveforms of uterine contraction were recorded. RESULTS: In terms of the writhing behaviors, the writhing latency in the Hegu (LI 4) group was extended significantly (P < 0.05, P < 0.01) and the writhing numbers in the Hegu (LI 4) group were decreased significantly (both P < 0.05) as compared with those in the Sanyinjiao (SF 6) group and in the Xuehai (SF 10) group. In terms of the waveforms of uterine contraction, compared with that in the model group, the amplitude and the activity of uterine contraction in both Sanyinjiao (SF 6) group and Hegu (LI 4) group were decreased significantly (all P < 0.05), and with no significant difference between the Xuehai (SF 10) and the model group (P > 0.05). CONCLUSION: For comprehensive assessment of the analgesic effect of electroacupuncture at different acupoints by using the writhing behaviors and the waveforms of uterine contraction, "Hegu" (LI 4) is the best, "Sanyinjiao" (SP 6) is the next and "Xuehai" (SP 10) is the third. showing a relatively functional specificity of the acupoint. PMID- 20578390 TI - [Chief physician SU Jia-Fu's academic experiences]. AB - Chief physician SU Jia-fu is engaged in clinical work for more than 40 years, forming his own unique acupuncture therapeutic method. He emphasizes the syndrome differentiation in terms of meridians and collaterals and taking unblocked transmission as normal functional state of six Fu-organs, and thinks that the affection characteristic and rule about the circulation parts of meridians and the pertaining organ should be known so as to guide acupuncture treatment; in manipulation of acupuncture, he emphasizes that the key is to grasp lifting and thrusting, twirling and rotating, and keeping vitality; in theatment, he attaches importance to blood-letting puncture from its methods, patients' reaction, blood volume and dynamic state of bleeding and emphasizes that this treatment has special efficacy in pain syndrome. PMID- 20578391 TI - [Debating on the formulation of standardized manipulation of acupuncture and moxibustion, Part I: Moxibustion]. AB - Main difficulties and solutions in working out the national standard Standardized Manipulation of Acupuncture and Moxibustion, Part I: Moxibustion are explained in this paper so as to promote the implementation and application of this national standard, including the definition of moxibustion, selection of pertinent literature, expiration date of moxa stick, quantification of moxibustion amount and the problems needing attention. PMID- 20578392 TI - [On dog-days sticking for treatment of heat syndrome: discussion on the draft of Guidelines on Clinical Application of Acupoint Sticking Therapy treating Winter Diseases in Summer]. AB - The information of Guidelines on Clinical Application of Acupoint Sticking Therapy Treating Winter Diseases in Summer suggests that acupoint sticking therapy treating winter diseases in summer is refer to deficiency-cold diseases and is not applicable to heat syndrome. According to the basic theories "maintaining yang in spring and summer" "correspondence between man and universe" in Internal Classic and combining the clinical practice, the authors then demonstrate the feasibility and necessity of dog-days sticking for treatment of heat syndrome, and expound the connotation of acupoint sticking with cold-natured or cool-natured herbal drugs and the clinical significance of dog-days sticking for treatment of heat syndrome. At the same time, the different opinion and expectation is put forward to further improve this therapy. PMID- 20578393 TI - [Explanatory clinical trials and pragmatic clinical trials on clinical effective evaluation of acupuncture]. AB - The concepts and relations of explanatory clinical trials and pragmatic clinical trials on randomized controlled trials of acupuncture are stated. The explanatory clinical trials and pragmatic clinical trials are different in the purpose of study, the controlled method, the treatment method and the solution problems. The explanatory clinical trials may enhance the understanding of the mechanism of a treatment; the findings of pragmatic clinical trials may be applied immediately in clinical practice. This paper explains that these clinical trials are of great importance to the methodology and practices of clinical effective evaluation of acupuncture based on TCM theory. PMID- 20578394 TI - [LUO Zhao-Ju: a famous expert of acupuncture and moxibustion]. AB - To introduce the contribution of LUO Zhao-ju an famous acupuncturist and educationist in Guangxi. After studying on his works and papers, LUO Zhao ju's contributions are promoting clinical acupuncture practices, promoting acupuncture education, acupuncture manipulation, improving acupuncture techniques, and reasonable practices according to the original theory of acupuncture and moxibustion. PMID- 20578395 TI - [Comprehension and explanation of meridians and collaterals theory in the background of the spread of western medicine into the East in the Ming and Qing Dynasties]. AB - In the background of the spread of western medicine into the East in the Ming and Qing Dynasties, Chinese doctors who had accepted western medicine referred to western medical knowledge and began to use the methods of anatomical observation and demonstrating to explain the objective structure of meridians and collaterals. They tried to adopt the artery and vessel explaining the shape of meridian and the blood circle and pulmonary respiration explaining the circulation of Ying-Wei. When the anatomy structures could not perfectly equal to meridians and collaterals, some doctors put forward the gasification feature of meridian to explain the reason. These results suggest that there are difference between meridians and collaterals and pure anatomy concepts, which serves as significant reference and edification for later generations. PMID- 20578396 TI - [Micro-acupuncture system in the hairline region of the scalp]. AB - Studying on the acupoints in the hairline region of the scalp, it is discovered that a group of acupoints are orderly arranged in the hairline region of the scalp. Furthermore, the arrangement is highly consistent with the meridian route of zang-fu organs. Manipulating needles at acupoints in the hairline regions of the scalp may treat certain diseases, including insomnia, migraine, and Alzheimer disease. The characteristics of the acupuncture treatment at acupoints in the hairline of scalp resemble the characteristics of ear acupuncture and eye acupuncture. Thus forms a special micro-acupuncture system in the hairline regions of the scalp. This paper states the theoretical basis, the arrangement of acupoints, clinical application and operating norms. PMID- 20578397 TI - [Analysis on indications and dominant diseases of acupotomology]. AB - To analyze the indications and dominant diseases of acupotomology by literature research. The findings reveal that the 64.4% of all literature focused on eight categories of diseases, including the third lumbar vertebrae transverse process syndrome, tendinitis stenosans, cervical spondylosis, heel pain, scapulohumeral periarthritis, external humeral epicondylitis, lumbar disc herniation and osteoarthritis. The 87.5% of all literature focus on diseases of chronic strain of movement system, cervical spondylosis, cervicogenic disease, lumbar disc herniation and osteoarthritis. The indications of acupotomology are various, but not evenly distributed; the dominant diseases are comparatively concentrated. The acupotomology has great potential to treat the indications and dominant diseases. Therefore, acupotomology should be promoted scientifically in the future. PMID- 20578398 TI - Perils of injudicious medical imaging: time for a wake-up call! PMID- 20578399 TI - Spectrum of intrabronchial mass lesions and role of flexible bronchoscopy in their diagnosis: a series of 74 cases. AB - BACKGROUND: Variety of benign and malignant lesions of respiratory system presents as intrabronchial mass lesions. Present study was carried out to study the spectrum of intrabronchial lesions and role of flexible flexible bronchoscopy in their diagnosis. METHODS: Retrospective study of case-records of patients with intrabronchial mass lesions diagnosed by flexible bronchoscopy, bronchial washings and bronchial biopsy between January 2004 and June 2006. RESULTS: Out of the 696 flexible bronchoscopies done during the study period, intrabronchial mass lesions were evident in 74 patients (10.6%) (age range 21-86 years; 60 males). Fifty (68%) lesions were malignant, eighteen (24%) lesions were benign while six (8%) lesions were inconclusive. Diagnostic yield was about 92%; repeat bronchoscopy for inconclusive results improved the diagnostic yield. CONCLUSIONS: Though malignant lesions are common, benign lesions remain important causes of intrabronchial mass lesions. Bronchoscopy with adequate sampling is an essential diagnostic modality for confirming the diagnosis of such lesions. PMID- 20578400 TI - Validation of a Hindi translation of Mini Asthma Quality of Life Questionnaire in north Indian patients with bronchial asthma. AB - BACKGROUND AND OBJECTIVE: There is little information on validated health-related quality of life (HRQoL) instruments for use in Indian patients with bronchial asthma. We attempted to validate the Hindi translation of Juniper's mini asthma quality of life questionnaire (MiniAQLQ) in north Indian patients with bronchial asthma. METHODS: Hindi translation of MiniAQLQ, and abbreviated World Health Organization quality of life questionnaire (WHOQOL-Bref), were administered to 30 patients with bronchial asthma twice at a six-week interval. Clinical and physiological data were also recorded. Psychometric properties (acceptability, validity, reliability and responsiveness) of MiniAQLQ were assessed after calculating four domain (physical, psychological, social relationships and environment), and a total score. RESULTS: Most questionnaires were returned without missing responses. MiniAQLQ had good convergent and discriminant validity, but moderate content and construct validity. All components (except emotional function domain) met standards for internal consistency (Cronbach's alpha coefficient >0.70), but intra-class correlation coefficients were variable. Change in MiniAQLQ scores between two assessments correlated poorly with corresponding changes in lung function. The effect sizes ranged from 0.02 to 0.34 in 11 patients whose forced expiratory volume in the first second (FEV1) changed by >200mL and >12% from baseline, and were considered small. CONCLUSION: The Hindi translation of MiniAQLQ is a moderately good discriminative and a relatively poor evaluative instrument to assess health related quality of life (HRQoL) in north Indian patients with bronchial asthma. PMID- 20578401 TI - Factors associated with non-adherence to specific allergen immunotherapy in management of respiratory allergy. AB - BACKGROUND: Non-adherence to specific allergen immunotherapy is a major hurdle faced by the allergist, contributing to poor clinical outcomes. OBJECTIVES: To assess the independent association of various factors with non-adherence to specific allergen immunotherapy. METHODS: Fifty consecutive (non-adherent) and control (adherent) subjects receiving specific allergen immunotherapy were included in the study and various factors related to non-adherence including socio-demographic, clinical and immunotherapy related variables were compared between the two groups by univariate and multivariate analysis. RESULTS: On univariate analysis, gender, allergic conjunctivitis, family history, progression of disease, perception of immunotherapy, medicine requirement, and the pattern of missed doses greater than two in the last 10, 20 and 30 doses were found to be significantly associated with non-adherence. On multivariate analysis, independent association was observed with allergic conjunctivitis, family history, perception of immunotherapy, missed doses greater than two in the last 10 doses of immunotherapy and medicine requirement. CONCLUSIONS: The independent factors associated with non-adherence may vary between different settings and countries. There is a need for developing individual case holding programmes to improve clinical outcomes in patients receiving specific allergen immunotherapy. PMID- 20578402 TI - Diagnosis and management bronchopleural fistula. AB - The diagnosis and management of bronchopleural fistula (BPF) remain a major therapeutic challenge for clinicians. It is associated with significant morbidity and mortality. Diagnosis and localisation of BPF is sometimes difficult and may require multiple imaging and bronchoscopies. Successful management of a fistula is combined with treatment of the associated empyema cavity. The first step, therefore, should be control of active infection and adequate drainage of the hemithorax. When deemed required, definitive surgical repair should be accomplished expeditiously, minimising the number of procedures performed. In cases of a small fistula or where the surgical risk is high, various bronchoscopic methods have been used to close the fistula. When treatment is protracted, secondary complications are more likely and survival is adversely affected. In this article, approaches to the diagnosis and treatment of BPF are discussed, with particular emphasis on bronchoscopic management options. PMID- 20578403 TI - H1N1 influenza pneumonia. PMID- 20578404 TI - Mediastinal haemangioma with pericardial effusion: a rare entity. AB - Mediastinal haemangioma is a rare benign vascular tumour. A young male presented with complaints of cough and dyspnoea. Serial chest radiographs were suggestive of progressive mediastinal widening and cardiomegaly. Pericardiocentesis revealed haemorrhagic fluid which was negative for microbiology and malignant cells. Patient was unresponsive to antituberculosis treatment and steroids. Computed tomography (CT) of thorax revealed an anterior mediastinal mass lesion with pericardial effusion which on biopsy was found to be a mediastinal haemangioma. PMID- 20578405 TI - Giant primary pulmonary fibrosarcoma. AB - A rare case of primary fibrosarcoma in a 48-year-old male is described who presented with a huge pulmonary mass on the left side. The diagnosis was established on fine needle aspiration cytology (FNAC) and percutaneous transthoracic lung biopsy, supported by immuno-histochemistry. PMID- 20578406 TI - Morgagni hernia with Down syndrome: a rare association. AB - We report a case of a 22-year-old male with Down syndrome and Morgagni hernia, who presented to us with complaints of cough, regurgitation and vomiting. He was successfully treated surgically and the defect was repaired with prolene mesh. PMID- 20578407 TI - Tracheopathia osteoplastica presenting with haemoptysis in a young male. AB - A young man presented with infrequent haemoptysis spanning over 10 years. Chest radiograph was normal. However, the computed tomography (CT) of the chest had shown endotracheal wall changes. The diagnosis of tracheopathia osteoplastica was suggested on fiberoptic bronchoscopy and confirmed histologically. PMID- 20578408 TI - United States life tables, 2005. AB - OBJECTIVES: This report presents period life tables by age, race, and sex for the United States based on age-specific death rates in 2005. The tables presented are based on a newly revised methodology. For comparability, all life tables from the year 2000 forward have been re-estimated using the revised methodology and are presented in the "Technical Notes" section. METHODS: Data used to prepare the 2005 life tables are 2005 final mortality statistics, July 1, 2005 population estimates based on the 2000 decennial census, and 2005 Medicare data for ages 66 100. The methods used to estimate mortality for ages 0-65 were the same as those used in annual life tables from 1997 through 2004 (1). The methodology to estimate mortality for the population aged 66 and over was revised in three ways: Medicare data were used to supplement vital statistics and census data starting at age 66 rather than 85, as was done from 1997 through 2004; probabilities of death based on current Medicare data rather than rates of change of probabilities of death based on noncurrent Medicare data were used; and the smoothing and extrapolation of the probabilities of death for ages 66 and over were performed using a nonlinear least squares model rather than a linear model of the rate of change of the probabilities of death for ages 85 and over (1-3). RESULTS: In 2005, the overall expectation of life at birth was 77.4 years, representing a decline of 0.1 years from life expectancy in 2004. From 2004 to 2005, life expectancy at birth remained the same for males (74.9), females (79.9), the white population (77.9), white males (75.4), white females (80.4), the black population (72.8), and black males (69.3). Life expectancy at birth increased for black females (from 76.0 to 76.1). Life expectancy estimates based on the revised methodology are slightly lower than those based on the previous methodology. For 2005, life expectancy at birth based on the revised methodology was lower by 0.4 years for the total population. PMID- 20578409 TI - Atherogenesis in rheumatoid arthritis: the "rheumatoid vasculopathy"? AB - BACKGROUND AND AIM: Rheumatoid Arthritis (RA) is associated with accelerated atherogenesis. RA patients have a reduced life expectancy compared to the general population, and cardiovascular (CV) disease (CVD) is recognized as a strong contributor to the excess of morbidity and mortality. Our aim was to review and discuss the recent advances in the knowledge of the RA-associated atherogenesis. METHODS: A detailed search of the available literature was performed in the PubMed (U.S. National Library of Medicine) database. RESULTS: Atherosclerosis is an early and common finding in RA patients, positively correlating to the disease duration and severity. Both traditional CV risk factors and disease-related mechanisms may contribute to the RA atherogenesis, however, clinical and epidemiological studies suggest that the systemic inflammation is the major determinant of the RA vascular comorbidity. Patients with RA show an increased risk for CV events compared with the general population, and CVD accounts for nearly 50% of death causes. CV morbidity and mortality strongly correlate with disease activity, whereas the successful pharmacological control of the chronic inflammation decreases the risk of CV complications. CONCLUSIONS: Atherogenesis is a precocious feature in RA, as extraarticular manifestation of the syndrome, and might be defined the "rheumatoid vasculopathy". The better understanding of molecular mechanisms leading to the RA accelerated atherogenesis, the development of effective screening methods, and the identification of successful strategies to control both systemic inflammation and concomitant CV risk factors will allow to minimize the rheumatoid vasculopathy impact on the patients' morbidity and mortality. PMID- 20578410 TI - A gust of WNT: analysis of the canonical WNT pathway. AB - The Wnt pathway is a signal-transduction cascade that mediates communication between cells; the Wnt pathway is involved in key steps during embryological development and in the maintenance of adult tissue homeostasis. Mutational dysregulation of Wnt cascade components has been observed in diverse human pathological conditions and in oncogenic transformations. For these reasons, the Wnt signalling pathway has acquired growing interest in scientific and medical research over recent years. This review outlines the biochemical and functional features of the Wnt cascade with particular emphasis on a detailed functional analysis of all key players. In this instance, the regulations of the pathway have also been covered, emphasizing novelty in this regard. Furthermore, past and present studies on Wnt have been included, as well as a prediction of scientific progress, which may be made in this rapidly evolving field, in the near future; the review also embraces considerations on how further understanding of the Wnt pathway will provide important insight into managing human diseases. PMID- 20578411 TI - Optimal fosamprenavir regimen to prevent lipid abnormalities. AB - We report our experience on the impact of different fosamprenavir boosted regimens on plasma lipid levels in 48 naive monoinfectd- HIV-seropositive patients. Eighteen months after starting antiretroviral therapy (ART), all patients showed a good immuno-virological response, with no statistically significant differences among the three groups; no changes in ART regimens were necessary and no adverse events were reported. On the contrary, a statistically significant difference among the three groups of patients was observed in cholesterol and triglyceride levels, since higher levels of cholesterol (including LDLs) and triglycerides were observed in patients taking the higher dose of ritonavir. (www.actabiomedica.it) PMID- 20578412 TI - Thyroid autoimmunity and type 1 diabetes in children and adolescents: screening data from Juvenile Diabetes Tuscany Regional Centre. AB - BACKGROUND AND AIMS: The incidence of autoimmune thyroiditis in patients with type 1 diabetes mellitus (T1DM) is higher than in healthy population. The aim of this study is to investigate epidemiology and natural history of thyroid autoimmunity (AIT), thyroiditis diagnosis and need for therapy in paediatric patients with T1DM and to find the most suitable timing of AIT screening. METHODS: T1DM patients (493 pts., 268 males and 225 females) treated in the Juvenile Diabetes Tuscany Regional Centre at Meyer's Children Hospital were enrolled to determine TSH, fT4, thyroid autoantibodies levels and to undergo thyroid ultrasound. Anamnestic data about T1DM onset, AIT onset, time frame between T1DM and AIT onsets and the relationship between AIT and celiac disease (CD) were studied. RESULTS: In the screened population 11.7% of patients presented with increased thyroid autoantibodies, and 63.6% of them showed positive thyroid ultrasound. AIT was significantly more frequent in females compared to males (p < 0.01). The mean age at AIT onset was 11.17 +/- 3.29 years (range 4.99-20, 30) and AIT onset before 12 yrs. of age was found in 54.5% of cases; 18.4% patients (all females) presented CD. The mean time between T1DM and AIT onset was 2.46 +/- 3.41 years (range 0-13, 41). The subgroup with increased thyroid autoantibodies was not statistically different from the whole population with regard to TDM1 duration and mean age at onset. CONCLUSIONS: AIT is frequently associated with T1DM (11.7%) regardless of age and duration of diabetes. We suggest a yearly screening for AIT after TDM1 onset, at every age. PMID- 20578413 TI - Evaluation of the patterns of diagnostic and therapeutic care for first referrals at the Parma Headache Centre. AB - BACKGROUND AND AIM OF THE WORK: To evaluate the patterns of care for patients referred for the first time to a Headache Centre. METHODS: A semistructured questionnaire was administered to all patients consecutively referred for the first visit to the Parma Headache Centre between 15 March and 28 September 2006. RESULTS: The study included 202 patients, 55 men (27.2%) and 147 women (72.8%), mean age 40.6 years (41.8 for men and 40.2 for women). In 146 patients (72.3%), no diagnosis was made before. In the 56 patients (27.7%) with a prior diagnosis, there was concordance only in 16 cases (28.6%). The most common reason to get treatment at the Centre was having a specialistic opinion(n = 81, 40.1%). Sixty two patients (30.7%) came for worsening of headache and 50 pts. (24.8%) for recent headache onset. Nine patients (4.4%) came for other reasons. Only in 98 cases (48.5%) the physician's prescription was correct with an explicit "visit at Headache Centre" request. The average waiting time was 191.1 days (range, 0-270). The most prescribed tests were EEGs (33.5%, i.e. 47.2% for men and 44.2% for women) and brain CT-scans (28.7%, i.e. 49% for men and 34.6% for women). Out of the 27 patients already taking tryptans, 25 were found to have migraine and two cluster headache. The prescription of tryptan was correct. Most patients were already taking NSAIDs (n =174, 86.1%). Only one female patient was taking ergot derivatives and antiemetics. CONCLUSIONS: Management of care should be improved to reduce waiting lists and unnecessary tests. PMID- 20578414 TI - Talar fractures: long-term results. AB - BACKGROUND: talar fractures are rare and potentially invalidating injuries. Traditional x-ray projections often do not provide comprehensive and exhaustive view of the talus; in order to determine the best therapeutic strategy and obtain early and precise prognostic data diagnostic examination usually includes oblique projections and computed tomography scans. In displaced fractures treatment is surgical, with percutaneous or open osteosynthesis. METHODS: 16 patients affected by talar fractures were treated and assessed with the Ankle Hindfoot Scale, the Ankle Osteoarthritis Scale and radiographic investigation. RESULTS: consolidation was obtained in all cases. None avascular bone necrosis was observed at the follow-up. Mean score divided into the two components was 69.3 on the first scale and 38.4% on the second scale. CONCLUSIONS: talar fractures are challenging injuries for orthopedic surgeon. The evolution of this type of fractures, above all in the most complex fractures of the body and of the neck, is often poor and characterized by severe complications. Early treatment is important for recovery. PMID- 20578415 TI - Rehabilitative and infiltrative treatment with hyaluronic acid in elderly patients with rotator cuff tears. AB - Rotator cuff tears are an important cause of disability. It is frequently observed in elderly people with a consequent loss of autonomy in daily life activities. The aim of this study is to evaluate the efficacy of the infiltrative treatment with hyaluronic acid, followed by a selective rehabilitative programme in elderly patients who do not present indications for surgical treatment. Twenty two patients were selected (14 men and 8 women), ranging from 70 to 89 years, (mean age 78.1) with rotator cuff tears. They underwent to a conservative treatment consisting in a series of 3 infiltrations (once a week) with hyaluronic acid (jointex starter molecular weight: 800-1200 kdalton) followed by a specific rehabilitative treatment (passive and active assisted kinesitherapy). Each patient was evaluated for pain through a Visual Analogic Scale (V.A.S.). Costant Murley and the Shoulder Rating Questionnairev were adopted to analyze the loss of range of motion of the shoulder as well as autonomy in daily life activities. The obtained results were statistically significant (p < 0.0005), both for the reduction of pain and for the improvement of range of motion and autonomy in daily life activities. The encouraging results obtained with this treatment could be considered as a valid choice instead of a surgical treatment in selected cases. PMID- 20578416 TI - Cytoreductive surgery and ovarian carcinoma. AB - PURPOSE OF INVESTIGATION: the aim of this study is to demonstrate if Cytoreductive surgery in patients with ovarian carcinoma increases overall survival. METHODS: during the period between 1998 and 2008, 60 patients with a relapse of ovarian cancer, were evaluated in order to undergo a cytoreductive surgery. RESULTS: an optimal cytoreduction (residual disease < 1 cm maximum diameter) was obtained in over half of patients. CONCLUSION: surgery remains the best therapeutic approach in ovarian cancer since it is associated with an increase in survival in all patients undergoing cytoreduction especially in the advanced stages of the disease. These results and those of other studies allow us to determine which patients may benefit from the cytoreductive surgery, improving their survival rate. A disease-free interval > 12 months is the best predictive factor of improved survival rate after surgery. PMID- 20578417 TI - Defunctioning stoma in high-risk rectal anastomosis. AB - BACKGROUND: Ileostomy in rectal surgery is not always indicated for protecting the anastomosis. METHODS: We examined patients who underwent low rectal resection surgery for carcinoma between June 2005 and December 2007. We categorized the patient's characteristics according to the American Society of Anesthesiologists (ASA). We estimated hospital stay, and postoperative Dukes stage. RESULTS: 68 patients, 47 males and 21 females (mean age 67.8 years, range 40-85 years) treated with low rectal resection for carcinoma. An ileostomy was performed in 29 out of 68 patients (42.6%). Six postoperative ileostomy cases led to the appearance of peritonitis from anastomotic fistula. Among the patients with ileostomy 19 pts. (65.5%) belonged to ASA II and 10 pts.(34.5%) to ASA III; among those patients without ileostomy, 32 (82.05%) ASA II and 7 (17.95%) ASA III (p = n.s.). Of patients who underwent the first protective surgical procedure, 4 belonged to ASA II (66.6%) and 2 to ASA III (33.3%). The mean hospital stay for the non ileostomy group was 7.64 +/- 0.7 days, while it was 7.36 +/- 0.49 (p = n.s.) for the ileostomy group. The mean stay of postoperative ileostomy for leakage was 10.83 +/- 1.16 days. CONCLUSIONS: Ileostomy cannot completely prevent the onset of leakage, but may reduce overall hospitalization time. PMID- 20578418 TI - Botox for chronic anal fissure: is it useful? A clinical experience with mid-term follow-up. AB - BACKGROUND: Sphincterotomy has been the most commonly used treatment for chronic anal fissures. Although effective it is associated with incontinence (0-20%). Intrasphincteric Botulinum Toxin A injection seems to be a reliable option. The aim of this clinical report is to verify the effectiveness of this treatment in relieving symptoms and healing fissures without relapse. METHODS: The study design was an open label non-comparative prospective trial to evaluate the efficacy ofbotulinum toxin injection in anal sphincters. In the period 2003-2005 sixty patients were enrolled in our Unit of Coloproctology. After inoculation hygiene measures (sitz baths, Vaseline oil and water intake) were recommended. After the first 4 weeks without improvement we administered a second injection (30 U.I). After failure of the second administration the patient was addressed to surgery. Mean follow-up was 24 months; patients were re-evaluated at the 6th, 12th and 24th month. RESULTS: In 29 pts the fissure was healed (48.33%) after the first injection; 31 patients (51.6%) were re-treated; 20 pts presented a complete healing of the fissure in a period ranging between 4-5 weeks from the second injection and 11 patients were introduced to surgery. In 3 cases we observed haemorrhoidal thrombosis. Gas incontinence was reported in two patients and solved spontaneously. CONCLUSIONS: Our clinical experience suggests that botulinum toxin therapy can be considered effective and safe. It can be proposed to the patient as first line therapy before surgery. PMID- 20578419 TI - Delineation of pulmonary airway fluid protein fractions with HRPO binding-avidity by far-Western ligand blot and mass spectrometry analyses: a model methodology for detecting mannose-binding protein expression profiles. AB - BACKGROUND AND AIM OF WORK: Limited research to date has characterized the potential for HRPO to function as a primary molecular probe. METHODS: Pulmonary airway fluid was developed by non-reducing far-Western (ligand) blot analyses utilizing conjugated HRPO-strepavidin or non-conjugated HRPO without the presence of primary immunoglobulin. Endogenous esterase-like biochemical activity of fractions within pulmonary airway fluid was inactivated to determine if they were capable of biochemically converting HRPO chemiluminescent substrate. Complementary analyses modified pulmonary fluid and HRPO with beta-galactosidase and alpha-mannosidase respectively, in addition to determining the influence of mannose and maltose competitive binding on HRPO far-Western (ligand) blot analyses. Identification of pulmonary fluid fractions detected by HRPO far Western blot analyses was determined by mass spectrometry. RESULTS: Modification of pulmonary fluid with beta-galactosidase, and HRPO with alpha-mannosidase in concert with maltose and mannose competitive binding analyses altered the intensity and spectrum of pulmonary fluid fractions detected by HRPO far-Western blot analysis. Identity of pulmonary airway fluid fractions detected by HRPO far Western (ligand) blot analysis were transferrin, dynein, albumin precursor, and two 156 kDa equine peptide fragments. CONCLUSIONS: HRPO can function as a partially-selective primary molecular probe when applied in either a conjugated or non-conjugated form. Some protein fractions can form complexes with HRPO through molecular mechanisms that involve physical interactions at the terminal alpha-mannose-rich regions of HRPO glycan side-chains. Based on its known molecular composition and structure, HRPO provides an opportunity for the development of diagnostics methodologies relevant to disease biomarkers that possess mannose-binding avidity. PMID- 20578420 TI - How to explain a PaO2 of 140 mmHg in a venous line? AB - Metformin is a commonly used oral antidiabetic drug which can cause lactic acidosis. Although rare, this condition carries a high mortality risk. Correction of metabolic acidaemia is essential for treatment and dialysis with bicarbonate replacement is the gold standard approach. A 53-year-old man with diabetes on metformin therapy was admitted to the intensive care unit with severe lactic acidosis and acute renal failure suggesting metformin intoxication. The lactic acidosis was treated with bicarbonate haemodialysis and his pH normalized after 10 hours, but he died because of myocardial infarction due to severe hypotension. At ICU admission an aortic dissection was also hypothesized but TEE did not evidence aortic dissection. The dilemma in this patient was represented by the abnormal PaO2 value (140 mmHg) in the venous blood gas analysis. Considering that metformin acts on mitochondrial respiration, the dilemma may be explained by hypothesizing a cellular respiration block caused by metformin or severe acidosis. (www.actabiomedica.it) PMID- 20578421 TI - Antiviral properties of antineoplastic drugs. From herpes simplex-1 disappearance to a wide antiviral action: a serendipity case report. AB - Herein we report the clinical case of a 46 year old female affected by lung cancer and cerebral metastases who showed, one month after the beginning of an oncologic therapy with vinorelbine and cisplatin, the complete remission of periodic (every 15 days) recurrences of herpetic mouth lesions. More than one year after the disappearance of the herpetic lesions, no further evidence of them were found. Subsequently, specific laboratory investigations, together with another case report that is presently in process, showed that vinorelbine, aside from its well known antineoplastic properties, also exerts a powerful antiviral action. PMID- 20578422 TI - Efficacy of intramuscular clodronate in Complex Regional Pain Syndrome type I: description of a case located in the astragalus in a patient with psoriatic arthritis. AB - Reflex sympathetic dystrophy or Complex Regional Pain Syndrome type I (CRPS I) is a painful regional disease with non-metameric topography, which shows extreme pathomorphological variability, from forms in which pain is the only clinical manifestation, to "pseudo-purulent" forms characterized by impressive local manifestations. The use of high doses of bisphosphonates in the treatment of CRPS I is confirmed in different publications which associate their efficacy with their specific biological properties and multiple actions at local level. This case report describes a case of CRPS I in the astragalus of a patient with psoriatic arthritis, successfully treated with intramuscular clodronate. PMID- 20578423 TI - Inveterate traumatic dislocation of the hip: a case report. AB - Abstract. The Authors report a case of inveterate dislocation of the left hip in a male patient of 23 years arrived at the "Centre de Reeducation Motrice" of Madagascar. The patient had an escape limping, important low back pain and limb dysmetria. He was treated with a hip arthrodesis considering the risks of infection and the economic problems of total prosthesis. We present a case of disappearance of pain and resumption of working activity. PMID- 20578424 TI - Total laparoscopic hysterectomy of an uterus of 1840 grams: a case report. AB - This case report describes a total laparoscopic hysterectomy of a large uterus of a woman who recently underwent neurosurgery for a grade IV glioblastoma. Because of a severe anaemia due to chronic vaginal haemorrhage for a fibromatosis uterus, she was not able to start a chemotherapic oncological protocol. We thus decided to perform a total hysterectomy through a laparoscopic approach in order to reduce the hospital stay and to ensure a quick recovery. We studied a surgical but also anaesthesiological strategy in order to obtain a good result with no or as few as possible complications. PMID- 20578425 TI - Gynecomastia disclosing diagnosis of Leydig cell tumour in a man with thalassemia, secondary hypogonadism and testis microlithiasis. AB - Aim of this paper is to report about a 35-year old man suffering from beta Thalassemia major and longstanding untreated hypogonadotropic hypogonadism, who was referred because of a recent onset and painful bilateral gynecomastia, with no palpable testicular masses. Due to the finding of a solid mass at left testis ultrasonography, monolateral testicular exeresis was performed and histology revealed a Leydig Cell Tumour and testicular microlithiasis. Post-surgical restoration of testosterone/estradiol ratio under testosterone therapy was followed by a very rapid reduction of gynecomastia. Our report confirms the usefulness of scrotal ultrasonography for finding an occult testicular tumour in a patient with painful and recent onset bilateral gynecomastia and underlines: a) the important role of testosterone/estradiol ratio in the pathophysiology of gynecomastia; b) the questionable significance of testicular microlithiasis as marker of testis tumours; c) the possible association between beta-Thalassemia and tumoral pathologies. PMID- 20578426 TI - Diagnosis of Henoch-Schonlein purpura in a child presenting with bilateral acute scrotum. AB - Schonlein-Henoch syndrome (HSP) is one of the manifestations of acute systemic vasculitis related to circulating immune complexes including IgA. It usually involves the kidney, gastrointestinal tract, joints and skin. Except for rare cases that progress to renal failure, it is a disease which heals without complications. The first case of male genital involvement in this syndrome was reported by Allen et al in 1960. Since then, several reports of this condition with an incidence of scrotal involvement varying from 2 to 38% have been described. The involvement of the male genitalia presenting as the only initial manifestation of SHS is so unusual that the diagnosis can easily be missed. In literature rare cases have been reported in which acute scrotum was the initial presenting symptom in patients affected by HSP. We report a case of HSP presenting as acute scrotum in a 5-year-old boy hospitalized for fever and viral bronchopneumonia. PMID- 20578427 TI - CT angiography of the coronary arteries: setting new diagnostic standards in cardiovascular medicine. AB - Abstract. CT Coronary Angiography of the heart is one of the fastly developing techniques in cardiovascular imaging. It is rapidly emerging and quickly entering the clinical practice and international guidelines. The increasing evidence regarding the strong role in the assessment of coronary artery lumen is progressively expanded by evidences of the important role of coronary wall imaging. The prognostic importance of CT Coronary Angiography is worldwide reported and the main question that is posed at the moment concerns the potential impact in primary prevention. In this review we will discuss the current applications and technology state of the art, X-ray dose issues, the training requirements and implementation in the healthcare context of CT Coronary Angiography. PMID- 20578428 TI - Letter to the editor about "Treatment of congenital anomalies in a missionary hospital in Bangladesh: result of 17 paediatric surgical missions". PMID- 20578429 TI - Sport injuries prevention strategy in active children. The Giocampus Barilla experience. PMID- 20578430 TI - The impact of the recession on employment-based health coverage. AB - HEALTH COVERAGE AND THE RECESSION: This Issue Brief examines changes in health coverage among workers during the recession that started in December 2007. Data from the Survey of Income and Program Participation are used to examine health coverage prior to the recession, and as recently as July 2009. Monthly changes are examined for 2007 and May 2008-July 2009, with emphasis on changes that occurred between September 2007 and April 2009. EMPLOYMENT-BASED COVERAGE STILL DOMINANT: Health coverage through the work place is by far the most common source of health insurance among the population under age 65. In 2008, 160.6 million individuals under age 65, or 61.1 percent of that population, were covered by employment-based health benefits. Fifteen percent were covered by Medicaid or the State Children's Health Insurance Program (SCHIP), 6.3 percent purchased coverage directly from an insurer, and about 3 percent were covered by Medicare or Tricare/CHAMPVA. Nearly 17.5 percent were uninsured. UNINSURED GROWING: Since the recession started in December 2007, the uninsured have grown. The unemployment rate was as low as 4.4 percent in May 2007, but by July 2009 it had reached 9.4 percent. The percentage of the nonelderly population with employment-based coverage was 61.3 percent in May 2007, and by July 2009 it was down to 58.2 percent. The uninsured rate was 12.3 percent in May 2007, and by July 2009 it was up to 16.4 percent. EMPLOYMENT-BASED COVERAGE ERODING: Between December 2007-May 2008, the percentage of workers with coverage in their own name (the policyholder) fell from 60.4 percent to 56.8 percent. The period between May 2008 July 2009 shows a continuing decline in the percentage of workers with employment based coverage in their own name, falling to 55.9 percent. CHANGES TO THE BENEFITS PACKAGE: The benefits that are being offered have also changed. Deductibles, copayments for office visits, and prescription drug copayments have been increasing. VULNERABLE POPULATION LOSES THE MOST: In general, workers least likely to have employment-based coverage at the beginning of the recession were more likely than other workers to experience a decline in the percentage with such coverage one year later. Younger workers were more likely to lose coverage than older workers. Hispanic workers were more likely to lose coverage than whites or blacks. Part-time workers were more likely than full-time workers to have lost employment-based coverage. EMPLOYMENT SECTOR: The percentage of workers with own name employment-based coverage declined the most among those employed by for-profit private-sector employers and those employed by the federal government. Workers with the lowest earnings were the least likely to have employment-based coverage in their own name and experienced the largest decline in coverage. PMID- 20578431 TI - Hans Loewald and the transformation of passion. AB - Loewald's writing is notable for its musicality as well as for its content. In this article, possible early determinants of this salient aspect of his work are discussed. The intensity of Loewald's regard for Freud and, in particular, his attentiveness to Freud's language are explored. Loewald's views on the legitimacy of transference as an ongoing aspect of human motivation is discussed, along with the possible emergence in Loewald's own writing of transferences toward Freud- both oedipal level conflicts regarding parricide and preoedipal concerns regarding unity and separation. Sublimation, a process Loewald viewed as an extension of internalization, is seen as foundational to his achievement. PMID- 20578432 TI - The "dreamer" by daylight: imaginative play, creativity, and generative identity. AB - This paper attempts to answer the question: Why, when most children play imaginatively, do so few go on to become creators? The author reviews ideas about the interplay between psychic reality, imaginative play, and creativity, elaborated by generations of researchers since Freud first linked these. The transformational process of play is seen to cultivate a multifaceted inner world and greater complexity of the creative capacity. Developmental themes, age specific preoccupations, and the changing nature of play are considered. The author's original contribution is the concept of "generative identity"-proposing that a young child's self-image is configured through growing distinctions of gender (components of which are redefined as embodiment, representation, desire). Generative identity is further consolidated by negotiating issues of generation (cohort), genesis (origins), generativity (procreation) and "genitive" issues separateness, arbitrariness, and the irreversibility of birth and death. PMID- 20578433 TI - The cosmic child: The artwork of Joseph Cornell and a type of unusual sensibility, or thinking inside the box: the mind that channels infinity. AB - This paper explores the unique mind of the twentieth- century American artist Joseph Cornell, known for his boxes and collages made with "found" materials. The author interpolates reflections upon Cornell with vignettes from the treatment of a young child, speculating that certain individuals may possess a constellation of vulnerabilities/sensitivities that constitute what is referred to as a "cosmic" sensibility. It is suggested that such an orientation can lead variously to anxieties and separation problems, as well as (or in addition to) intellectual and/or artistic giftedness. The outcome of such dynamics would depend on a complex interplay of temperament, circumstance, and relational attunement. PMID- 20578434 TI - The princess has to die: representing rupture and grief in the narrative of adoption. AB - The search for a coherent account of one's life and one's origin may become a particularly powerful organizer of fantasy and memory, affect and conflict, self and object representation in adopted children. Yet relinquishment, unacknowledged affects, and inaccessible history create a rupture in the fabric of that narrative. Clinical material is presented to illustrate the impact such disruptions may have on the personal narrative and the developing selfhood of the child, with a particular focus on the impact of inhibited mourning. The evolving play showed that grieving facilitated representation of losses and discontinuities and made possible a more integrated representation of the self. PMID- 20578435 TI - The use of fantasy play in the treatment of a six-year-old adopted girl. AB - The traditional psychoanalytic practice with children focuses on the observation and the interpretation of the child's play. In contrast, in my treatment of Sara, my focus was on playing with the child. Since initially she was unable to play, Ifirst taught her how to act out fantasies in play until, gradually, she became an active participant and, finally, the creator of her own stories. This method was effective because it reproduced the "to and fro" or "optimal responsiveness" between the mother and infant in the first three years of life when the infant/child experience is of being found by the mother. Like the infant/child, my patient's response to our playing was to recognize that her actions evoked meaning for her therapist. Empowered by this selfawareness, she began to participate in the dialogue of fantasy play and, as our stories expanded, she experienced the affirmation and fulfillment of a reciprocal relationship. While lost in play, she experienced being found. Her story demonstrates, poignantly, how a child comes to choose aggression and cruelty as a source of power. For Sara, nurturing and goodness engendered feelings of weakness and helplessness because they stirred up her envy of and intense longing for the good enough mothering that she had never known. PMID- 20578436 TI - Play and the older child: developmental and clinical opportunities. AB - This paper examines the meaning and function of pretend play in older children. First, a review of the widely accepted developmental sequences, growth-promoting potential, and analytic uses of play for younger children is provided. Then the possible role for play in later childhood is explored through the presentation of Sarah, a twelve-year-old girl in analysis, whose play appeared to provide both clinical and developmental benefits. The suggestion is made to soften the existing developmental line for play in order to allow for its role with preadolescent children. PMID- 20578437 TI - Two people playing together: some thoughts on play, playing, and playfulness in psychoanalytic work. AB - Children's play and the playfulness of adolescents and adults are important indicators of personal growth and development. When a child is not able to play, or an adolescent/adult is not able to be playful with thoughts and ideas, psychotherapy can help to find a more playful and creative stance. Elaborating Winnicott's (1968, p. 591) statement that "psychotherapy has to do with two people playing together," three perspectives on play in psychotherapy are discussed. In the first point of view, the child gets in touch with and can work through aspects of his or her inner world, while playing in the presence of the therapist. The power of play is then rooted in the playful communication with the self In a second perspective, in play the child is communicating aspects of his or her inner world to the therapist as a significant other. In a third view, in "playing together" child and therapist are coconstructing new meanings. These three perspectives on play are valid at different moments of a therapy process or for different children, depending on the complex vicissitudes of the child's constitution, life experiences, development, and psychic structure. Concerning these three perspectives, a parallel can be drawn between the therapist's attitude toward the child's play and the way the therapist responds to the verbal play of an adolescent or adult. We illustrate this with the case of Jacob, a late adolescent hardly able to play with ideas. PMID- 20578438 TI - A clinical study of the intergenerational transmission of eating disorders from mothers to daughters. AB - Clinicians and researchers have long recognized the existence of eating disorders in very young children, including infants whose mothers have eating disorders. This paper combines reviews of the literature relevant to the study of eating disorders from the perspectives of both research and psychoanalytic theory in order to explore the psychodynamics of the intergenerational transmission of eating-disordered pathology from mother to child. A developmental pathway as well as several mechanisms that illuminate the pathogenesis of the intergenerational transmission of eating disorders are proposed and described. Clinical observational data from a therapeutic play nursery for mothers with eating disorders and their children are presented, and this material is examined in relation to the proposed psychodynamic pathways of transmission. PMID- 20578439 TI - The joke envelope: a neglected precursor of the psychic envelope concept in Freud's writing. AB - The concepts of the primeval skin ego, psychic envelope, and related pre-ego containing and wrapping functions elaborated respectively by Esther Bick, Didier Anzieu, and Francis Tustin occupy an important position in contemporary psychoanalytic theory and clinical practice. The psychic envelope begins as a virtual mental protostructure ("proto" because it is not yet based on fully symbolized representations) that holds the budding mind together pending further developments. With maturity, the enveloping functions adopt symbolized, metaphoric form (for example, the aesthetic use of cloth, the analytic framework), but can regress to more concrete and pathological forms. The aforementioned authors based their ideas on a cluster of specific allusions to the idea of a psychic covering, barrier, or envelope in Freud's work. Yet they neglected one reference, hidden in Freud's analysis of the structure ofjokes and humor: the 'joke envelope"--die witzige Einkleidung. The present essay explores Freud's use of the term Einkleidung, including his intriguing idea that a joke requires three people whereas a dream does not and the fact that Freud nowhere speaks of a "dream envelope. "I take the "joke envelope" beyond its original context and posit a relationship between laughter and the early, normative traumas of breathing, crying, and loss, and the dawn of rhythmic envelopes that enable mentalization. Jokes and joking symbolically repeat the early rupture and rapture of breathing and self-other differentiation and the internalization of maternal containing and envelopment. PMID- 20578440 TI - A proposal to revive "parent guidance": an illustration of a brief intervention with the mother of a toddler. AB - A parent guidance intervention is illustrated. The value of such work is underscored to help parents and candidates in child analysis understand intergenerational psychopathology and its consequences for a child. Technical considerations of parent guidance are addressed. A revival of such work is advocated in child analysis training programs. PMID- 20578441 TI - The contribution of the analyst's actions to mutative action: a developmental perspective. AB - The concept of action has evolved since Freud's initial attempts to adticdress the topic. It is no longer viewed as just serving a defensive function. Instead it is increasingly seen as a mode of experiencing and n, communicating, one that is less developmentally advanced than the verbal one usually emphasized in psychoanalysis. Research from many fields documents the view that experiencing, thinking, and communicating originate in bodily action. Hence psychoanalysts have learned to use the patient's actions to broaden their understanding of the patient and to deepen the analytic process. But they have been slower to apply this understanding to their own actions. This paper uses an extended clinical vignette of an action intervention by the analyst to demonstrate its importance in maintaining and deepening an analytic process. It then suggests a theoretical and clinical rationale that such action interventions are a common and necessary aspect of most analyses. Finally it raises the question of whether such interventions can be regarded as interpretations offered at the developmental level being used by the patient to communicate at particular moments in analysis. Can they be viewed as the initial interpretation in the process of interpretation? PMID- 20578442 TI - Using context to treat traumatized children. AB - When treating childhood psychic trauma, context means "putting a perspective to the terrifying experience"--"seeing it in a new light", one might say, or understanding its magnitude and meaning. Of three essential mechanisms behind a young person's psychological recovery from a stress disorder--abreaction, context, and correction-context is the most reflective, cognitive, and conscious of these processes; while abreaction is primarily emotive, and correction is primarily behavioral (involving real or fantasied action). Because context, newly introduced by this author to the psychiatric literature (Terr, 2003), is the most recent and the least well understood of the three mechanisms, it will be the sole focus here. PMID- 20578443 TI - Introduction to Hansi Kennedy's "Children in conflict: Anna Freud and the war nurseries". PMID- 20578444 TI - Introduction to Hansi Kennedy's "Children in conflict": an appreciation. The Anna Freud Centre perspective. PMID- 20578445 TI - Children in conflict: Anna Freud and the War Nurseries. 1995. PMID- 20578446 TI - The relentless past: The effect of chronic sexual abuse in childhood on fifty years of adolescent and adult development. AB - Four sisters, now in their late fifties and early sixties, were sexually abused during childhood over a four-year span by the same priest. Until recently they told no one about their experience and never received any psychological diagnostic evaluations or treatment. The author conducted detailed psychiatric evaluations of each of the four women while serving as the plaintiffs' expert witness during their lawsuits against the Catholic Church. The suits have been settled, and the women have given written permission to tell their stories. This unique clinical material provides a rare opportunity to describe and understand the ongoing, pervasive effects of untreated, chronic childhood sexual abuse on developmental processes over half a century. In each instance the women were describing the details of the abuse and the effects on their development for the first time. The severity of the pathology and the intense shame and anxiety associated with discussing their experiences after so many years raises questions about the choice of treatment and technique, particularly in regard to transference and countertransference issues. PMID- 20578447 TI - Early diagnosis and treatment of falciparum malaria in Cambodian trauma patients. AB - Asymptomatically infected patients with falciparum malaria may develop symptomatic malaria infection secondary to injury or surgery. This complication increases the risk for postoperative wound infection and adds to the burden of trauma. The aims of the present study were to investigate the preventive effect of early antimalaria treatment of Plasmodium falciparum infected trauma patients, and to study the validity and accuracy of a rapid test to identify those infected. An open, non-randomized, interventional multi-center, cohort study was carried out at six district hospitals in northwestern Cambodia. Two hundred twenty-two trauma patients was examined for P. falciparum by dipstick test soon after injury. The patients testing positive were immediately treated with artesunate-mefloquine. A subset of 108 patients from Pailin, an area considered highly endemic for falciparum malaria, was used for the main analysis. Of 28 P. falciparum rapid test-positives, 21 developed symptomatic postinjury malaria despite early antimalarial treatment. The agreement between the dipstick test and blood smear examination was good (kappa 92.5; 95% CI 84.5-100). Early pre operative treatment of parasite carriers does not seem to prevent symptomatic malaria after injury and surgery. The rapid test for falciparum malaria was reliable in early identification of asymptomatic P. falciparum infected patients. PMID- 20578448 TI - Migrants and malaria risk factors: a study of the Thai-Myanmar border. AB - The objective of this study was to investigate factors influencing self-reported malaria among migrants living along the Thai-Myanmar border. Songkaria Village, with 1600 inhabitants and 290 households in Sangkhla Buri District, Kanchanaburi Province, was selected for the study due to its intense malaria transmission. One hundred twenty-five households were randomly selected. Household members were interviewed about the history of malaria, socioeconomic status and knowledge and practices in regard to malaria using a structured questionnaire. Of the respondents, 10%, 42%, and 48% belonged to the Thai, Mon, and Karen ethnic groups, respectively. About 40 % of Thai and Karen migrants and almost 30% of Mon migrants reported having suffered from malaria at least once. Multivariate analysis focused on migrants. The results identified three independent factors for previous malaria: a high risk occupation, ie working primarily in the forest [odds ratio (OR), 3.55; 95% confidence interval 1.3-10.0], ability to read Thai [OR, 4.13 (1.5-11.7)], and correct knowledge about malaria symptoms [OR, 5.18 (1.1-23.5)]. Working conditions among migrants played a major role in acquiring malaria. They could not afford to apply additional preventive measures, such as using a mosquito net or repellent to be used while working. The concept of enhancing the environment for migrants to enable them to protect themselves against malaria needs to be examined. Ways and means of improving the economic conditions of migrants should be considered to minimize exposure to the vector. PMID- 20578449 TI - Toxoplasmosis in HIV/AIDS: a living legacy. AB - Toxoplasmosis has historically been considered one of the most important opportunistic infections detected in HIV/AIDS patients. The prevalence rates of latent Toxoplasma infections in HIV-infected patients has been found to vary greatly from 3% to 97%. Prevalence has been found to be related to ethnicity, certain risk factors, and reactivation of toxoplasmosis. Prior to antiretroviral therapy, toxoplasmic encephalitis (TE) was the most common focal cerebral lesion detected in AIDS patients with Toxoplasma infection, occurring in approximately half of Toxoplasma-seropositive patients. Other forms of dissemination have also been reported in AIDS patients in sites such as the eyes, lungs, heart and spinal cord. Anti-Toxoplasma therapy and chemoprophylaxis have shown effectiveness in reducing the incidence of TE, while noncompliance has been identified as a cause of relapse in these settings. Toxoplasmosis is one of the most common neuropathological complications found at autopsy. Rapid progress in the development of highly active antiretroviral therapy (HAART) has changed the observed patterns with TE, for which there has been a marked decrease in overall incidence. Subsequently, TE has been found to be significantly associated with the so-called "neurological immune restoration inflammatory syndrome" (NIRIS). Toxoplasma screening programs are recommended for all newly diagnosed HIV positive patients. Chemoprophylaxis should be considered in HIV-infected patients who have a CD4 < 200 cells/mm3, particularly in settings where resources are limited and there is not access to HAART. TE remains a cause of morbidity and mortality among AIDS patients. PMID- 20578450 TI - Acute respiratory distress syndrome in Plasmodium falciparum malaria. AB - Acute respiratory distress syndrome (ARDS) as a complication of malaria infection is rare but with a very high mortality rate. We report the case of a patient who developed high fever, then respiratory distress during a trip to Haiti who was admitted to our hospital and diagnosed with malaria. During recovery the patient developed ARDS in the hospital. PMID- 20578451 TI - Undiagnosed amebic brain abscess. AB - We report a case of amebic brain abscess due to Entamoeba histolytica. The patient was a 31-year-old man who presented with amebic liver abscess. His clinical course deteriorated in spite of proper drainage and treatment. He developed delirium, lethargy and then expired. With a history of heroin addiction, withdrawal syndrome from heroin was suspected. At autopsy, amebic abscesses were detected in the liver, large intestine, meninges and brain. A 19 cm amebic liver abscess was found in the right lobe of the liver. A 4 cm amebic brain abscess was found in the right occipital lobe. Microscopically, the tissue sections from the affected organs were confirmed to have degenerated E. histolytica trophozoites. Involvement of the brain in amebic liver abscess should be suspected in patients with neurological signs and symptoms. PMID- 20578452 TI - Evaluation of anti-leishmanial activity by induction of nitric oxide and inhibition of prostaglandin in Balb/c mice infected with Leishmania major. AB - Cutaneous leishmaniasis is still one of the health problems in Iran and in the region. Nitric oxide (NO) has a key mechanism in the elimination of parasite from the body by its anti-leishmanial activity. Prostaglandin (PG) is a critical inhibitory factor of infected macrophage to decrease their anti-leishmanial activity. This study was designed to induce NO by L-arginine (L-Arg) precursor and inhibit PG production by anti-inflammatory Indomethacin (INDO) in Leishmania major infected Balb/c mice, in order to evaluate the effects of NO and PG on delay of lesion formation, size of lesion and proliferation of amastigotes inside macrophages. Liver, spleen and lymph nodes were also studied as target organs to detect amastigotes. Serum, liver and spleen suspensions were investigated for NO induction by using Griess microassay and serum PG was determined by ELISA. The results indicated that NO production was inhibited by Leishmania in infected Balb/c mice as compared with naive animals. Serum NO was inhibited by a combination therapy of L-Arg and INDO. Although NO was decreased in the liver by L-Arg, however it increased in the spleen after L-Arg and INDO application. A significant decline was observed in lesion size from Week 6 after infection by INDO. Both L-Arg and INDO had significant inhibitory effects on visceralization of leishmania in target organs. Only L-Arg decreased proliferation of promastigotes in macrophages. Pathophysiological signs including hepatomegaly, splenomegaly, survival rate and body weight all were affected in this experiment. Statistical analysis of data revealed an association between NO induction and PG inhibition in leishmaniasis. These data may indicate a possible candidatory for L Arg and INDO as novel drugs for the treatment of leishmaniasis in mouse model. PMID- 20578453 TI - Ultrastructural effects of albendazole on the body wall of Gnathostoma spinigerum third stage larvae. AB - This study investigated the effects of albendazole (ABZ) on the ultrastructure of Gnathostoma spinigerum advanced third-stage larvae. Two groups of experimentally infected mice received 60 or 90 mg/kg ABZ orally once a day for 21 consecutive days. Both groups had damage to the body walls of the worms, especially to the non-contractile part of the muscular layer. The severity of the damage was dose related, the higher the dose, the greater the damage. The body wall of the ABZ treated larvae demonstrated a decrease in the number of mitochondria in the non contractile muscular part, especially in the internal surface of the sarcolemma. Some mitochondria developed large vacuoles, and became distorted and degenerated. The nuclei degenerated and had irregular shapes and the number of glycogen granules decreased. The present study demonstrates the structural damage induced by the toxic effects of ABZ and increases our knowledge of the mechanism of action of ABZ against G. spinigerum. PMID- 20578454 TI - Effect of curcumin on pathogenesis of hamster-opisthorchiasis through apoptosis related gene expression. AB - The present study investigated the effect of curcumin, a phenolic compound with yellow color from Curcuma longa L., on the expression of the apoptosis-related genes [BAX (Bcl-2 associated protein X), PKB, p53, MDM2 (mouse double minute 2), caspase 9, c-Ski, smad1 and smad4] in hamster opisthorchiasis. On Opisthorchis viverrini infection treated with dietary curcumin apoptosis-related gene expression profiles were similar to O. viverrini-infected group, but the expression levels seemed lower. Light microscopic observation revealed that aggregation of inflammatory cells surrounding the hepatic bile ducts in the groups infected with O. viverrini and treated with dietary curcumin was lower than in infected group. The intensity of the response is correlated with expression of the genes studied. The results suggest that curcumin reduces pathogenesis in hamster-opisthorchiasis by controlling apoptosis-related gene expression. PMID- 20578456 TI - Residual effect of 10% bifenthrin wp on mosquitoes, and community acceptance, in eastern Thailand. AB - This study was conducted from May to October 2008 in two villages in Chanthaburi Province: village No. 2 Tup Sai Canton (control) and village No.12 Pong Nam Ron (treatment area). Indoor residual spraying, using 10% bifenthrin WP (Bitecthrin WP) was conducted at a concentration of 25 mg/m2 with 87.3% spray coverage of the houses in the treated area. Monthly entomological studies showed that in the control area, Anopheles minimus density was significantly higher than the treatment area. A WHO cone bioassay test showed the residual effect against laboratory-bred, An. dirus persisted for up to 6 months. Community acceptability was good and most preferred insecticide spraying. 10% bifenthrin WP applied six monthly can be used as an indoor residual spray for malaria control. PMID- 20578455 TI - Molecular identification of larval trematode in intermediate hosts from Chiang Mai, Thailand. AB - Snail and fish intermediate hosts were collected from rice fields in 3 districts; Mueang, Mae Taeng and Mae Rim of Chiang Mai Province during April-July 2008. For identification of larval trematode infection, standard (cracked for snail and enzymatically digested for fish) and molecular methods were performed. The results showed that three types of cercariae were found, pleurolophocercus, cotylocercous, and echinostome among 4 species of snail with a prevalence of 29, 23 and 3% respectively. Melanoides tuberculata snail was the most susceptible host for cercariae infection. Four species of metacercariae, Haplorchis taichui, Stellantchasmus falcatus, Haplorchoides sp and Centrocestus caninus, were found with a prevalence of 67, 25, 60 and 20%, respectively. The Siamese mud carp (Henicorhynchus siamensis) was the most susceptible fish host for H. taichui, and half- beaked fish (Dermogenys pusillus) for S. falcatus metacercariae infection, whereas Haplorchoides sp and C. caninus were concomitantly found in Puntius brevis. HAT-RAPD profile confirmed that pleurolophocercus cercariae found in Melanoides tuberculata from Mae Taeng District belonged to H. taichui and in Tarebia granifera from Mueang District were S. falcatus. PMID- 20578457 TI - Efficacy of commercial household insecticide aerosol sprays against Aedes aegypti (Linn.) under simulated field conditions. AB - A simulated field study on the efficacy of commercial household aerosol insecticides was conducted. The bioefficacy of three pyrethroid aerosols, designated as PA1, PA2 and PA3, was tested in cabins furnished to simulate bedroom conditions. Each aerosol product was tested against lab-bred Aedes aegypti mosquitoes based on the insecticide manufacturers' recommended dosages. Ten cages with mosquitoes were placed in the following locations: one cage in the middle of the room; two each on and underneath the bed; three each placed inside, behind and on top of the wardrobe; and four placed on and in the desk. With the desk, each cage was placed inside each of three drawers (totally closed, partially closed and opened). Prior to the experiments, the discharge rate of each aerosol can was determined. Ten to 20 lab-bred 2-5 day-old sugar-fed Ae. aegypti adult mosquitoes were placed inside the test cages. The aerosol was then discharged into the cabin at the recommended dosage. After 30 minutes, the mosquitoes were transferred into clean paper cups and their mortality recorded after 24 hours. All the aerosols induced complete or very high mortality in the caged Ae. aegypti females, except in the cages hidden completely inside the drawers and wardrobes. Insecticide droplet analysis indicated variable uniformity of the droplets was produced. The aerosol insecticides were effective against mosquitoes provided they were used in accordance with the manufacturers' recommendations. PMID- 20578458 TI - Intramolecular integration assay validates integrase phi C31 and R4 potential in a variety of insect cells. AB - Phage phi C31 and R4 integrases are site-specific and unidirectional serine recombinases. We have analyzed the ability of these integrases to mediate intramolecular integration between their attB and attP sites in 7 important insect cell lines as a means of predicting their relative mobility in the corresponding insect species. Both integrases exhibit significantly higher frequencies in Drosophila S2 cells than in the other insect cell lines examined, but do work well in all of the species tested. Our results, coupled with previous results of the activity of phi C31 integrase in D. melanogaster and Aedes aegypti, suggest the family of serine catalyzed integrases will be useful site specific integration tools for functional genome analysis and genetic engineering in a wide range of insect species. PMID- 20578459 TI - Development of single-tube mutiplex RT-PCR for dengue virus typing. AB - This study evaluated a single-tube multiplex RT-PCR with a primer focusing on nonstructural protein region 5 (NS5) and a highly conserved region for dengue virus serotyping. The method was compared with conventional PCR. This new method had a sensitivity of 96.7% and a specificity of 96.7% for disease detection. The new method also proved suitable for use in the field as it reduces time and decreases risk of contamination. PMID- 20578460 TI - Hemoptysis in children with pandemic influenza H1N1 2009 infection. AB - Three patients were admitted to Hat Yai Hospital, Songkhla Thailand with hemoptysis. They were previously healthy children aged 6, 13, and 14 years old who had attended schools in which outbreaks of influenza had occurred. They all had a history of fever, rhinorrhea, and severe cough accompanied by hemoptysis. Two developed hemoptysis on Day 3 and the third on Day 6 of illness, with one of them displaying massive hemoptysis. Chest radiographs were compatible with viral pneumonia in two cases and the third case was unremarkable. Coagulation profiles in the severe case were carried out and were normal. All the patients responded very well to treatment with oseltamivir and did not require intubation. Their subsequent nasopharyngeal swabs were positive for human pandemic influenza A H1N1 by real-time reverse transcription-polymerase chain reaction (RT-PCR), and their sputum for acid-fast bacilli and tuberculin skin tests were negative. PMID- 20578461 TI - Multi-drug resistant TB and HIV in Thailand: overlapping, but not independently associated risk factors. AB - The HIV and multi-drug resistant tuberculosis (MDR-TB) epidemics are closely linked. In Thailand as part of a sentinel surveillance system, we collected data prospectively about pulmonary TB cases treated in public clinics. A subset of HIV infected TB patients identified through this system had additional data collected for a research study. We conducted multivariate analysis to identify factors associated with MDR-TB. Of 10,428 TB patients, 2,376 (23%) were HIV-infected; 145 (1%) had MDR-TB. Of the MDR-TB cases, 52 (37%) were HIV-infected. Independent risk factors for MDR-TB included age 18-29 years old, male sex, and previous TB treatment, but not HIV infection. Among new patients, having an injection drug use history was a risk factor for MDR-TB. Of 539 HIV-infected TB patients in the research study, MDR-TB was diagnosed in 19 (4%); the only significant risk factors were previous TB treatment and previous hepatitis. In Thailand, HIV is common among MDR-TB patients, but is not an independent risk factor for MDR-TB. Populations at high risk for HIV-young adults, men, injection drug users - should be prioritized for drug susceptibility testing. PMID- 20578462 TI - Multiple fractures of the symphysis pubis due to tuberculous osteomyelitis. PMID- 20578463 TI - Dissemination of class I integron in Acinetobacter baumliannii isolated from ventilator-associated pneumonia patients and their environment. AB - Multidrug resistant Acinetobacter baumannii has become the most common cause of health care-associated infections at Maharaj Nakhon Si Thammarat Hospital, Thailand. The objective of the study was to detect integrons using PCR-based method from 96 A. baumannii isolates from ventilator-associated pneumonia (VAP) patients and their environment. Antibiotic susceptibility was determined using a disk diffusion technique. Forty-six isolates exhibited integrase genes, with only class I and class II integron detected in 43 and 3 A. baumannii isolates, respectively. Twenty-seven of 52 clinical and 19 of 44 environmental isolates were integron-positive. Detection rate of integron-positive A. baumannii isolated from VAP patients increased from 25% to 83% over the 4 month study period. The majority (91%) of integron-positive A. baumannii showed resistance to 6 or more of 11 antibiotics tested and 72% of class I integron-positive isolates were imipenem-resistant. Thus, class I integron-positive A. baumannii had spread among the VAP patients and into hospital environment, the latter acting as reservoirs of potential pathogens possessing drug resistance genes. PMID- 20578464 TI - Pneumocystis pneumonia among HIV patients in Malaysia. AB - Pneumocystis pneumonia (PCP) has become the most common opportunistic infection in HIV/AIDS patients with a CD4 count < or = 200. The incidence of PCP has declined as a result of prophylaxis and better highly active antiretroviral therapy (HAART). The objective of this study was to review the demographic data of HIV patients diagnosed clinically as having PCP at the Hospital Raja Perempuan Zainab II (HRPZ II) in Malaysia. This was a prospective study. All HIV patients admitted to HRPZ II with respiratory symptoms were enrolled in this study after giving informed consent. Their demographic data were collected. The total number of HIV patients reviewed in this study was 107. Nearly 60% of patients were clinically diagnosed as having pneumocystis pneumonia based on their signs, symptoms and chest x-ray findings. A CD4 count was available in 83 out of 107 patients. The fifty-three percent of patients(44) had a CD4 < 200 and were clinically diagnosed as having pneumocystis pneumonia. Thirty percent had a CD4 < 200 but did not have clinical pneumocystis pneumonia. Sixteen point nine percent had a CD4 > 200 and had clinical pneumocystis pneumonia, three of whom had received HAART, four patients had received prophylaxis. Overall, 94 patients (87.8%) received prophylaxis for pneumocystis pneumonia. Thirty-three patients (30.8%) received HAART. The occurrence of pneumocystis pneumonia was common before full implementation of HAART. Pneumocystis pneumonia can occur in patients with a CD4 >200. PMID- 20578465 TI - Evaluation of an in-house immunoperoxidase staining assay for histodiagnosis of human pythiosis. AB - Pythiosis, a life-threatening infectious disease of humans and animals in tropical and subtropical countries, is caused by the fungus-like organism Pythium insidiosum. As diagnosis of pythiosis is difficult, delayed diagnosis of pythiosis leads to poor prognosis. We developed an immunoperoxidase staining assay using rabbit anti-P. insidiosum antibodies to detect P. insidiosum directly in infected tissues of 19 patients with vascular (n = 11), ocular (n = 7) or cutaneous (n = 1) pythiosis. Tissue sections from 31 patients with various fungal infections were included as controls. Tissue sections from all pythiosis patients and 2 patients with Fusarium infections were stained positive, whereas the other 29 control sections were stained negative. Sensitivity and specificity of the assay was 100% and 94%, respectively. Based on the prevalence of human pythiosis (2%), calculated positive predictive value and negative predictive value was 24% and 100%, respectively. Thus, the diagnostic value of this assay is for ruling out pythiosis. The assay requires routine laboratory equipments and can easily be performed by pathologists in rural hospitals where the disease is more prevalent. PMID- 20578466 TI - Prevalence and risk factors of overweight and obesity in Turkish academic staff. AB - Obesity and overweight are a significant public health problem that affects the quality of life of the individuals concerned. We studied the prevalence and related risk factors for obesity among academics. This descriptive cross sectional study sampled 499 academic staff at Elazig Firat University, Turkey. Height, weight and blood pressure values were obtained and a descriptive survey was conducted. The age range of the participants was 22 to 65 years, with a mean age 36.5 +/- 8.1 years. The group had 29% women, and 71% men; 80% were married. The mean BMI of the participants was 24.6 +/- 3.1 kg/m2. Their mean systolic blood pressure was 117.0 +/- 12.1 mmHg and mean diastolic blood pressure was 73.1 +/- 8.0 mmHg. The overall prevalence of obesity was 7.0%; 2.1% in women and 9.0% in men. The combined prevalence of overweight and obesity was 45.9%. Nearly half the participants were either obese or overweight. A correlation was identified between overweight/obesity and sex, marital status, academic staff, physical activity, systolic and diastolic blood pressure. Although the study did not include all academics, the results reveal the need to evaluate the health impact of obesity in academics. PMID- 20578467 TI - Response rate of Malaysian blood donors with reactive screening test to transfusion medicine unit calls. AB - Blood donors with reactive screening test results are requested to come in for counseling by letter and telephone call. It has been noticed many donors responded to neither the letters nor the telephone calls. We evaluated 589 cases with reactive screening test results (208 positive for hepatitis C, 209 for hepatitis B, 85 for VDRL and 87 for HIV). In the hepatitis C positive group 61 donors (29.3%) did not respond and 4.7% missed their follow-up appointment. Similarly low response rates were noted with the HBV (58.9%) and VDRL (67.1%) positive groups. Among HIV positive donors 46.0% failed to respond to multiple calls. We conclude that blood donors in Malaysia have a poor response to calls from the blood transfusion unit. A review of the effectiveness of the current deferral system and an increased public knowledge of transmissible infectious diseases may encourage blood donors to have a better response rate. PMID- 20578469 TI - A traditional Malay myth leading to unintentional self intoxication with kecubung fruit. AB - Traditional Malay herbal medicine is still used in Malaysia especially in rural areas, instead of using modern medicine. Datura or "kecubung" has been used to treat allergic rhinitis in certain places. Inaccurate doses can potentially cause severe or fatal neurologic anti-cholinergic toxidromes. A good knowledge of toxidromes with optimization of supportive care can prevent fatal complications and lead to a more speedy recovery. We present a case of kecubung poisoning. PMID- 20578468 TI - Demographic and clinical characteristics of red tag patients and their one-week mortality rate from the emergency department of the Hospital Universiti Sains Malaysia. AB - Early identification and rapid treatment of red tag patients may decrease morbidity and mortality. We examined the clinical characteristics, etiologies and one week mortality rate of red tag (life threatening and potentially life threatening illness) patients at the Hospital Universiti Sains Malaysai (HUSM). A cross-sectional study was conducted at the Emergency Department of the HUSM from 1 August 2006 to 31 January 2007; 440 eligible patients were analyzed. The group had a mean age of 47.2 +/- 22 years, with 67.3% of the patients being male. Twenty-three percent were trauma cases with motor vehicle accident being the major mechanism of injury. Fifty-four percent of the cases had cardiac related illnesses. The mean duration of stay in the Emergency Department (ED) was 3.9 +/- 1.5 hours. The survival rate at one week was 76.6%. The non-trauma group comprised 74.0% of death cases. Acute coronary syndrome and road traffic accidents comprised 22.0% of total death cases at one week. Red tag patients constitute a large proportion of ED cases and may remain in the ED for significant periods of time. PMID- 20578470 TI - Health-seeking behavior among HIV-infected patients treated for TB in Thailand. AB - In Asia, patients increasingly seek tuberculosis (TB) treatment in the private sector; however, few private sector practices follow international TB management guidelines. We conducted a study to measure the frequency and predictors of seeking TB diagnosis in the private sector among 756 HIV-infected TB patients in four Thai provinces during 2005-2006. Of enrolled patients, 97 (13%) first sought care at a private provider and 83 (11%) at a pharmacy. In multivariable analysis, the only factor independently associated with seeking care at a private provider was having a high TB stigma score. Factors independently associated with seeking care at a pharmacy included not knowing that TB can be cured and that TB care can be provided close to home. Patients reported that the most influential factor in choosing a provider was confidentiality (468; 62%). Further research is needed to evaluate whether educating the community about the confidentiality, availability, and success of curing TB at government health facilities can promote prompt utilization of public TB treatment services by HIV-infected patients in Thailand. PMID- 20578472 TI - Prevalence and factors associated with stress among secondary school teachers in Kota Bharu, Kelantan, Malaysia. AB - The teaching profession is an occupation at high risk for stress. This research attempted to determine the prevalence of stress and the associated factors contributing to stress among teachers in Malaysia. A cross-sectional study was conducted on 580 secondary school teachers in Kota Bharu District. The instrument used to carry out the study was adopted and modified from the Depression, Anxiety and Stress Scale (DASS 21) and Job Content Questionnaire (JCQ). The questionnaire consisted of two parts: Part I consisting non-job factors (socio-demographic characteristics) and Part II consisting of psychosocial factors contributing to stress. Simple and multiple linear regression analysis were carried out. The prevalence of stress was reported as 34.0%. Seventeen point four percent of teachers experienced mild stress. Age, duration of work and psychological job demands were significantly associated with stress level. This study indicates job related factors did not contribute much to stress among secondary school teachers. Non-job-related factors should be further studied to determine methods for stress reduction in teachers in Malaysia. PMID- 20578471 TI - Used and foregone health services among a cohort of 87,134 adult open university students residing throughout Thailand. AB - There are limited data on the frequency of foregone health service use in defined populations. Here we describe Thai patterns of health service use, types of health insurance used and reports of foregone health services according to geo demographic and socioeconomic characteristics. Data on those who considered they had needed but not received health care over the previous year were obtained from a national cohort of 87,134 students from the Sukhothai Thammathirat Open University (STOU). The cohort was enrolled in 2005 and was largely made up of young and middle-age adults living throughout Thailand. Among respondents, 21.0% reported use of health services during the past year. Provincial/governmental hospitals (33.4%) were the most attended health facilities in general, followed by private clinics (24.1%) and private hospitals (20.1%). Health centers and community hospitals were sought after in rural areas. The recently available government operated Universal Coverage Scheme (UCS) was popular among the lower income groups (13.6%), especially in rural areas. When asked, 42.1% reported having foregone health service use in the past year. Professionals and office workers frequently reported 'long waiting time' (17.1%) and 'could not get time off work' (13.7%) as reasons, whereas manual workers frequently noted it was 'difficult to travel' (11.6%). This information points to non-financial opportunity cost barriers common to a wide array of Thai adults who need to use health services. This issue is relevant for health and workplace policymakers and managers concerned about equitable access to health services. PMID- 20578473 TI - Effect of different transfusion regimens on craniofacial appearance and dentition in severe thalassemic children. AB - Thalassemia is a group of inherited diseases with a defect in the synthesis of hemoglobin. Severe thalassemic subjects suffer from craniofacial deformities and malocclusion due to bone marrow hyperplasia compensating for ineffective erythropoiesis. Blood transfusions are used to maintain life and reduce complications. The transfusions may have benefits in reducing craniofacial and dentition abnormalities. However, appropriate therapy is still controversial. This study evaluated the effect of different transfusion regimens on craniofacial appearance and dentition. Ninety-two severe thalassemic patients, aged 6 -13 years, were divided into 3 groups according to the frequency of transfusion: 1) high transfusion: more than 12 times/year. 2) low transfusion: 6-12 times/year. 3) occasional transfusion: less than 5 times/year. The appearance and dentition were evaluated and compared among groups. Most subjects in the high transfusion group had a normal appearance and a class I molar and incisor relationship with normal overjet and overbite. More than half of subjects in the low and occasional groups showed craniofacial abnormalities and malocclusion, particular in the occasional group. Frequency of transfusion has an effect on craniofacial appearance and dental occlusion; only high frequent transfusions were effective in preventing craniofacial and dental defects. PMID- 20578474 TI - Predictions of gas-particle partitioning coefficients (K(P)) of polycyclic aromatic hydrocarbons at various occupational environments of Songkhla Province, Thailand. AB - Ambient air samples were collected over periods of 24 hours and 3 hours using a Graseby-Anderson high volume air sampler with PM10 TE-6001 at 15 sampling sites, including an urban residential zone, rural area, industrial factories, waste incinerator, traffic areas and agricultural burning areas in Songkhla Province, Thailand. An analysis of organic carbon and elemental carbon was conducted to estimate the gas-particle partitioning of PAHs using a model proposed by Dachs Eisenreich. The estimated LogK(P) of PAHs emphasized the risk for lung cancer among outdoor workers in waste incinerators, traffic intersections and bus terminals, suggesting the role of the carbonaceous fraction over the gas-particle partitioning of PAHs. Analysis of f(SC)K(SA)delta(OCT)/F(OM)K(OA) ratios revealed a significant role of adsorption and absorption in unusually high elemental carbon fractions (ie low OC/EC ratio) in fine particles collected at waste incinerators and the abnormally high organic carbon fractions (ie high OC/EC ratio) observed in those fine particles of an urban residential zone, respectively. The dual mode of ab/adsorption tended to dominate the gas-particle partitioning of LMW PAHs collected at the traffic intersections and bus terminal. PMID- 20578475 TI - Awareness about kala-azar disease and related preventive attitudes and practices in a highly endemic rural area of India. AB - This study was undertaken to assess the extent of community awareness and related practices about kala-azar undertaken by them to control the disease, in an highly endemic focus of Bihar, India. A household-based cross-sectional knowledge, attitude, and practices (KAP) survey consisting of quantitative components on knowledge, attitude, and practices concerning kala-azar was administered to heads of-household through a semi-structured questionnaire. Data indicated that 61% respondents were illiterate, 4% had correct knowledge that sandfly bites caused kala-azar, 26% do not know any specific transmission agents for kala-azar. A majority (72%) of respondents were not able to recognize sandfly, 33% had no specific knowledge about the symptoms. All of them (100%) believed that this disease could affect his or her family income. Nearly all (95%) were positive that the kala-azar cases could be reduced with implementation of proper health measures. A few (11%) suggested isolation of patients to avoid contacting kala azar while a high proportion (93%) of respondents favored specific allopathic medicine, and a majority (72%) favored the utilization of the services offered by primary health centers or government hospitals. Just over half (66%) of the respondents were not using any prevention measures to avoid contacting disease. These results could prove to be useful for health planners in developing suitable control strategies. PMID- 20578476 TI - Epidemiology of Toxoplasma gondii infection of stray cats in Bangkok, Thailand. AB - The objective of this study was to investigate the epidemiology of toxoplasmosis in stray cats in Bangkok. Sera were collected during 2006 and examined by Sabin Feldman dye test. Five hundred sixty-four male and 926 female cats in and around monasteries from 50 districts were collected. Toxoplasma gondii was detected in 72 (4.8%) of 1,490 cats. The prevalence was significantly higher in females (5.6%) than in males (3.6%). Cats more than 5 years old had the highest infection rate (5.1%). Fifty-six percent (28/50) of areas were positive for T. gondii in cats. Our results show T. gondii is widespread in stray cats in Bangkok. It is essential to control the number of stray cats in order to reduce the transmission of toxoplasmosis to animals and humans. PMID- 20578477 TI - Management of Plasmodium knowlesi malaria without PCR confirmation. AB - Plasmodium knowlesi morphologically resembles P. malariae; PCR assays are able to differentiate between the 2 species correctly. However, PCR is not available in many hospitals in P. knowlesi endemic areas, particularly in Southeast Asia. In places where PCR is not available, anti-malarial drugs for P. malariae or other non-P. falciparum or P. falciparum species are effective against P. knowlesi. Even with a wrong diagnosis of another malaria species by light microscopy instead of P. knowlesi, the antimalarial drugs given are still effective for treating P. knowlesi infection. PMID- 20578478 TI - Gastrointestinal manifestations in severe strongyloidiasis: report of 3 cases and literature review. AB - We report here three cases of severe strongyloidiasis in normal and immunocompromised hosts. The first was a patient with a normal immune system who presented with acute severe abdominal pain. The second and third patients were immunocompromised due to steroid and chemotherapy treatment of underlying diseases. Both presented with obstructive symptoms. In all three cases, Strongyloides stercoralis larvae were detected in stool concentration samples, and in biopsied specimens from the duodenum in the first and second cases. PMID- 20578479 TI - Copro-DNA diagnosis of Opisthorchis viverrini and Haplorchis taichui infection in an endemic area of Lao PDR. AB - The utility of differential copro-DNA diagnosis using modified sample preparation steps of small liver and minute intestinal fluke infections was tested. Fecal samples containing parasite eggs were washed extensively with diluted detergent solution. Parasite eggs were concentrated by sedimentation and broken by microwaving before DNA extraction. PCR targeting ITS1 and ITS2 regions were performed using primer specific for Opisthorchis viverrini, Haplorchis taichui and other related species. Of 125 fecal samples, 94 were positive for small trematode eggs by a modified cellophane thick smear method. By ITS1-PCR, 52 samples were positive for O. viverrini, 12 H. taichui and 7 mixed infection. By ITS2-PCR, 63 were positive for O. viverini, 17 H. taichui, and 19 mixed infection. The ITS-PCR assay identified a higher number of opisthorchiasis cases than those with O. viverrini expelled after treatment, but for H. taichui, ITS PCR identified less than half of the worm expelled cases. These results showed that copro-DNA diagnosis was useful for the differential diagnosis of O. viverrini and H. taichui infection, which could not be discriminated by microscopy. PMID- 20578480 TI - Prevalence of Opisthorchis viverrini infection in the canine and feline hosts in three villages, Khon Kaen Province, northeastern Thailand. AB - To determine the current reservoir status and prevalence of Opisthorchis viverrini infection in endemic areas, 78 dogs and 22 cats were sampled for fecal examination in 3 villages along the Chi River in Khon Kaen Province, northeastern Thailand. Sex, age, color, identifiable markings, subjective body condition scores (BCS) and diet were recorded and analyzed. Fecal samples were evaluated using direct smear and modified formalin-ethyl acetate fecal assays. All parasites found were identified. In dogs and cats, the prevalences of O. viverrini infection were 3.8% and 36.4%, respectively. The highest prevalences of parasitic infection in both dogs and cats were Ancylostoma spp, in 64.1% and 77.3%, respectively. These results provide insight into the role of the canines and felines in maintaining the presence of O. viverrini eggs in the environment. If similar patterns occur on a broader scale, the zoonotic role of dogs and cats in the epidemiology of this disease should be considered in the development of improved control and education programs. PMID- 20578481 TI - Identification of blood meal of field caught Aedes aegypti (L.) by multiplex PCR. AB - Laboratory bred female Aedes aegypti (L.) was used to determine sensitivity of multiplex PCR for detecting human blood meal. Human blood DNA was detected in live fully fed mosquitoes until 3 days after blood feeding, and for 4 weeks when stored at -20 degrees C. Among 890 field caught female mosquito samples examined for vertebrate DNA by multiplex PCR, results were positive for human, pig, dog, cow and mixture of 2 host DNA at 86.1, 3.4, 2.1, 1.0 and 3.6%, respectively, while 3.9% of the samples were negative. Blood feeding pattern must be considered when mosquito control strategies become employed. PMID- 20578482 TI - Snails and trematode infection after Indian Ocean tsunami in Phang-Nga Province, southern Thailand. AB - The tsunami and non-tsunami affected areas of Takua Pa District, Phang-Nga Province were investigated for fresh- and brackish-water snails that transmit human parasitic diseases during 2006 and 2007. Among 46 snail species found, 17 species of 8 families were freshwater snails, 28 species of another 7 families were brackish-water snails, and 1 species was a land snail. Of these species, 11 freshwater snails, 4 brackish-water snails and 1 land snail were of medical importance. The fresh-water snails were Pomacea canaliculata, Pila angelica, P. gracilis, P. polita, Filopaludina (S.) martensi, F. (F.) s. polygramma, Melanoides tuberculata, Indoplanorbis exuxtus, Radix rubiginosa, Helicorbis umbilicalis, Gyraulus convexiusculus. Four brackish-water snails were Cerithidea cingulata, C. djadjarensis, C. alata, Sermyla riqueti and Achatina fulica was the land snail. I. exutus, M. tuberculata and F. (F.) s. polygramma harbored Xiphidio, Microcercus, Furocercus, Echinostome cercariae, and cercaria without eyespots or tail with hair. Three species of brackish-water snails, Cerithidia cingulata, C. djadjariensis, and C. alata presented with 6 types of trematode cercariae and rediae. Knowledge of medically important snails and their parasitic diseases, and prevention were given to Takua Pa people by poster, pamphlets and broadcasting through community radio. PMID- 20578483 TI - The eye fly Siphunculina funicola (Diptera: Chloropidae) as a carrier of pathogenic bacteria in Thailand. AB - The oriental eye fly Siphunculina funicola (1.0-1.6 mm) is extremely annoying to humans and domestic animals, feeding on mucous membranes, secretions, wounds, eyes, and other moist surfaces of the host body. In many rural areas of Thailand heavy populations of this fly prevail where they aggregate on a variety of hanging substrates, such as strings, nest trailings, electrical lines, decorations, ropes, cob webs, clothes hangers, automobile radio antennae and other items in open shade close to their hosts. Both males and females feed voraciously on wounds and moist skin. With this type of persistent feeding, the eye flies are suspected to carry and transfer germs to their hosts. In the present study, bacteria were isolated from S. funicola captured from wounds, host seeking flies and from their resting sites. Some enriched and bacterial culture media were more suitable for isolation than others. A diverse group of bacteria (64 species), both gram-posi-tive and gram-negative, most in risk category 2, were identified. Bacterial colony counts from Trypic soy broth ranged from 10 to > 3.0 x 10(3) cfu/ml. The most common bacteria isolated were Acinetobacter, Aeromonas, Bacillus, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Kocuria, Pantoea, Pseudomonas, Staphylococcus and others. These bacteria may cause disease conditions in humans and animals. This is the first time bacteria from S. funicola have been reported. PMID- 20578484 TI - Electrolyte disturbances and abnormal urine analysis in children with dengue infection. AB - Serum electrolytes and urine analysis results were retrospectively reviewed in children with either dengue fever (DF) or dengue hemorrhagic fever (DHF). Children who had positive serology for dengue infection and serum electrolytes determined before starting intravenous fluid were included in the study. During the years 2004-2007, 73 DF patients, age 9.29 +/- 3.62 years, and 77 DHF patients, age 10.04 +/- 3.64 years were enrolled in the study. The patients were admitted to the hospital on average on days 4.12 +/- 1.1 and 4.25 +/- 1.4 of febrile illness for DF and DHF, respectively. The prevalence of hyponatremia in patients with DF was 61% and DHF was 72% (p = 0.149). The mean serum sodium levels in patients with DF and DHF were 133.5 +/- 3.52 and 133.5 +/- 3.20 mEq/l (p = 0.938), respectively. The prevalence of hyponatremia in patients with mild (grade I), moderate (grade II) and severe (grade III-IV) DHF were 70, 77, and 78% (p = 0.729), respectively, and the mean serum sodium levels were 134.1 +/- 3.05, 132.9 +/- 3.33, and 132.5 +/- 3.28 (p = 0.189), respectively. The prevalence of hypokalemia in patients with DF was 14% and 17% in patients with DHF (p = 0.588). A high urine specific gravity reflecting dehydration was found in 63% of patients with DF and 60% of patients with DHF (p = 0.77). The prevalences of hematuria in patients with DF and DHF were 18% and 27% (p = 0.182), respectively and proteinuria were 15% and 27% (p = 0.072), respectively. The prevalences of hematuria and proteinuria were not different among patients with mild, moderate and severe DHF. No patients had gross hematuria or developed acute renal failure requiring dialysis. Mild hyponatremia is a common electrolyte disturbance and renal involvement is mild in patients with DF and DHF. PMID- 20578485 TI - Knowledge levels about Crimean-Congo hemorrhagic fever among midwifery and nursing students in Kahramanmaras, Turkey. AB - The aim of this study was to determine the knowledge levels of students in the Midwifery and Nursing Departments of the School of Health Sciences in Kahramanmaras Sutcuimam University (KSU) about Crimean-Congo hemorrhagic fever (CCHF) and to examine the factors influencing those knowledge levels. The study was conducted between April-June 2009 in the School of Health Sciences, KSU, Turkey. All the midwifery and nursing students in the School of Health Sciences at that time, 296 individuals, were included in the study. Questionnaire forms, developed from literature data and comprised of 66 questions, were given to the students, and they were asked to fill them out. Twenty-four point seven percent of the students were not available, thus 223 students(75.3%) were included in the study. Seventy-five point three percent of students stated a viruse was the cause for CCHF, 78.9% stated CCHF is seen between April and September in Turkey, and 80.7% stated there was no vaccine avaiable against it. Ninety-three point three percent of the study group stated that CCHF was transmitted by tick bite, 75.8% and 53.4% stated CCHF can be transmitted by exposure to blood of an infected animal or direct contact with an acutely infected animal, respectively. Thirty three point two percent of students stated CCHF had no specific treatment. The mean knowledge score of students regarding CCHF was 54.6 +/- 14.8. The CCHF scores of the nursing students were significantly higher than those of the midwifery students. The CCHF knowledge scores did not vary by age or college year. PMID- 20578486 TI - Clinical profile of chikungunya sequelae, association with obesity and rest during acute phase. AB - The scarcity of literature regarding chikungunya infection sequelae makes it an unexplored area of medicine. We analyzed 1,111 patients with confirmed chikungunya sequelae and found a female predominance in those with sequelae which increased with age up to 40-50 years old, then decreased with further increase in age. In males age > 60 years old was the predominant age group affected. The symptoms were mainly symmetrical polyarthralgia of the proximal and distal interphalangeal joints. Dermatological manifestations were mainly hyper pigmented patches, generalized pruritus, and a maculopapular rash. Insomnia, fatigability and headache may indicate neurological involvement. Obesity gave an odds ratio of 2.07 for risk of arthritis. There was no significant benefit from rest during the acute phase (p < 0.001) of chikungunya in preventing chronicity of sequelae. Obesity as an independent risk factor for chronicity of chikungunya infection sequelae is a new finding. PMID- 20578487 TI - Evaluation of a rapid assay for detection of IgM antibodies to chikungunya. AB - Chikungunya (CHIK) is a re-emerging disease causing a large negative impact on global health and economics. Clinical manifestations of CHIK are non specific and difficult to differentiate from dengue hemorrhagic fever or other viral exanthema. A rapid, simple and reliable diagnostic assay is necessary for CHIK outbreak control especially in countries with insufficient access to well equipped laboratories. The aim of the study is to evaluate a commercially rapid, qualitative CHIK diagnostic assay based on specific IgM antibody detection. Performance of the rapid assay was evaluated in comparison with semi-nested RT PCR and IgM detection by ELISA. The sensitivity of the rapid assay was not constant but positively correlated with duration of symptoms. If the test was conducted within the first week, sensitivity and specificity was 22% and 88%, respectively. If the patients were tested after the first week, sensitivity was increased to 83% while specificity was decreased to 71%. Thus, the rapid assay should not be used as a screening tool during the first week of CHIK due to its low sensitivity. PMID- 20578488 TI - A description of influenza-like illness (ILI) sentinel surveillance in Cambodia, 2006-2008. AB - Influenza-Like Illness (ILI) sentinel surveillance was initiated by the Communicable Disease Control Department (CDC), Ministry of Health, Cambodia and its partners to evaluate the epidemiology of influenza and identify the circulating strains. The surveillance started in late 2006 in four sentinel sites. The objectives of this study were 1) to document the incidence of LI and confirmed influenza cases reported in the national surveillance system from 2006 to 2008, just after the system and the definition were revised, 2) to identify the strains of influenza virus, 3) to compare the major demographic and clinical characteristics between ILI patients having positive and negative tests for influenza virus. An ILI case was defined as having a fever of at least 38 degrees C (axillary), cough or sore throat. A total of 155,866 ILI cases were reported to the CDC from 4 sentinel sites in Cambodia from August 2006 to December 2008. Specimens were collected in 1.8%. Of these, 9.6% tested positive for influenza. Influenza was observed to occur mainly from August to December, with a clear seasonal peak in October, as shown in the data from 2008. A new case definition beginning in August 2008 resulted in a decrease in weekly RI reported cases (from an average of 1,474 cases to 54 cases) and the proportion of positive tests for influenza increased (5.3% vs 29.3%). Influenza and ILI are seasonal in Cambodia. A higher body temperature was used to define ILI, which improved the influenza positivity rates. PMID- 20578489 TI - Detection of hepatitis A virus and bacterial contamination in raw oysters in Thailand. AB - This study was conducted to determine the presence of hepatitis A virus (HAV) in raw oysters (Crassostrea belcheri) using a virus concentration method and reverse transcription-nested polymerase chain reaction (RT-nested PCR). A total of 220 oyster samples were collected from oyster farms and local markets in Thailand. HAV was found in three oyster samples. Nested PCR products of HAV detected in oysters were characterized further by DNA sequencing of the VP1/2A region and subjected to phylogenetic analysis. All HAV sequences (168 basepairs) were associated with human HAV subgenotype IB (GIB). Fecal coliforms and Escherichia coli were determined using the multiple tube fermentation method, to assess the microbiological quality of collected oysters. Among oyster samples tested, 65% had fecal coliforms higher than the standard level for raw shellfish [< 20 Most Probable Numbers (MPN)/g]; MPN values in the range of 21.0-4.6 x 10(4)/g. Most oyster samples (85%) were contaminated with E. coli in the range of 3.0-4.6 x 10(4) MPN/g. One oyster sample with an acceptable level of fecal coliforms contained HAV GIB. E. coli was found in all HAV-positive oyster samples. The results suggest a significant presence of HAV and bacterial indicators of fecal contamination in raw oysters, which are a health risk for consumers and a source of gastrointestinal illness. Enteric viruses should also be tested to assess the microbiological quality of oysters. PMID- 20578490 TI - Cost-effectiveness of rotavirus vaccination as part of the national immunization program for Thai children. AB - Rotavirus infection is a common cause of gastroenteritis in infants and thus, presents an economic burden. Currently, there are effective vaccines against rotavirus licensed for use in Thailand. We evaluated the cost-effectiveness of rotavirus vaccination as part of the national immunization program for Thai children based on information derived from studies of disease burden of rotavirus infection, vaccine effectiveness, expenditure for care according to the WHO CHOICE; average GNP per capita provided by the Bank of Thailand and statistics from the Ministry of Health. The hypothesis of economic cost-effectiveness administering the vaccine along with DPT and OPV at ages 2 and 4 months was derived from a 5-year cohort study of 96% vaccinated children. Evaluation of vaccine cost-effectiveness included reduction of disease burden, cost averted, incremental cost-effectiveness ratio (ICER) to disability adjusted life year (DALY) averted and cost per life saved. Routine rotavirus immunization would prevent 109,918 visits to outpatient departments, 46,542 hospitalizations and 419 deaths in children under 5 years of age. It could reduce cost of care by USD12,066,484 or USD13 per child. As part of the national immunization program, the vaccine would be cost-effective at the direct medical break-even price of USD6.2 per dose. At a maximum vaccine price of USD6.2-10.5 per dose, the cost effectiveness ratio is approximately USD185-759 per DALY averted. Vaccine price is greatly influenced by vaccine efficacy, mortality and G genotypes of rotavirus. Rotavirus vaccination could reduce gastroenteritis in children but the price, if used as part of the national immunization program should be below USD10 per dose. PMID- 20578491 TI - Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART). AB - This observational cohort study was conducted among HIV-infected, antiretroviral therapy (ART) naive children in Phnom Penh, Cambodia, to evaluate the feasibility and efficacy of highly active antiretroviral therapy (HAART) delivered using a modified directly observed therapy (MDOT) protocol. From August 2004 to March 2006, 26 children were enrolled and started on a first-line HAART regimen, which was continued for 18 months. The study included a directly observed therapy phase (months 1-3) and a medication self-administration phase (months 4-18). CD4 percentage (CD4%) and HIV-1 RNA plasma viral load (PVL) were measured at baseline and at months 6, 12, and 18. At baseline, the median age was 5.5 years (range: 13 months-12 years), the median CD4% was 4, and the median PVL was 7.5x10(5) copies/ml. At 18 months, 23 (88%) children were alive and participating in the study. Of these children, 20 (87%) had a PVL <400 copies/ml and 12 (52%) had PVL < 50 copies/ml. The median CD4% increased to 23, while the median change in height-for-weight z-score was 0.64. Genotypic resistance typing in 2 children with PVL > 400 copies/ml at 18 months demonstrated mutations associated with resistance to lamivudine (M184V) and non-nucleoside reverse transcriptase inhibitors (Y181C and G190A). The virologic and immunologic outcomes achieved in this study compare favorably with those reported by other pediatric HIV treatment programs worldwide. The study results suggest that MDOT may be effective for HAART administration in limited-resource settings like Cambodia. PMID- 20578492 TI - Immune reconstitution inflammatory syndrome in adult human immunodeficiency virus infected patients in Thailand. AB - Immune reconstitution inflammatory syndrome (IRIS) is an important adverse event among human immunodeficiency virus (HIV)-infected patients taking highly active antiretroviral therapy (HAART). The epidemiology of IRIS in Thailand has not been well examined, especially among adult HIV-infected patients. In the present study, we reviewed the medical records of 174 HIV-infected, antiretroviral therapy-naive patients older than 15 years (the median CD4 count at commencement of HAART was 37 cells/mm3) and compared characteristics of patients with and without IRIS. During a 12-month follow-up period after commencement of HAART, 11 cases (6.3%) of IRIS were identified (4.2/100 patient-years HAART). The cases included nine cases with mycobacterial infection, one with cytomegalovirus retinitis and one with cryptococcal meningitis. The patients with IRIS were significantly younger than those without IRIS (29 vs 36 on medians, p = 0.022). The median interval between commencement of HAART and the onset of IRIS was 22 days. Although all patients with IRIS improved with or without corticosteroids, they were more frequently hospitalized during a 12-month follow-up period while taking HAART (1 vs 0 on medians, p < 0.001). The incidence of IRIS in advanced adult HIV-infected patients in Thailand was lower than that reported from Europe and the United States, which may be attributable to deferment of HAART after diagnosing opportunistic infections. PMID- 20578493 TI - ZAP-70 positive cells in treated and untreated HIV-1 infected patients. AB - ZAP-70 is a critical protein tyrosine kinase in T-cell activation and proliferation processes. Defective recruitment of ZAP-70 molecules results in termination of the T-cell receptor (TCR) signal transduction pathway. Impairment of this pathway is one of the early markers of disease progression in HIV-1 infected individuals. T-cell dysfunction in HIV infected patients may be connected to a defect in the proximal TCR signaling cascade. To evaluate this presumption, the numbers and mean fluorescence intensity (MFI) of ZAP-70 positive cells in patients with treated and untreated HIV-1 infection and healthy controls were analyzed by flow cytometry. A correlation between the MFI in ZAP 70 molecules and the viral load was evaluated. A total of 41 HIV-1 infected patients, 30 patients on HAART and 11 untreated patients, and 11 healthy controls were enrolled. The data show ZAP-70+/CD4+ cells in treated and untreated HIV-1 infected individuals had a greater MFI of ZAP-70 molecules than those from healthy controls (p < 0.001). The inverse correlation between the percentage of CD4+cells and the MFI of ZAP-70+/CD4+ T-cells was significant (r = -0.5; p < 0.01). A stronger correlation between the percentage of CD4+/CD25+ cells and the MFI of ZAP-70+/CD4+ cells was observed (r =-0.6; p < 0.01). However, no significant correlation was seen between the MFI of the ZAP-70+/CD4+cells and the viral load in patients with untreated HIV-1 infection (r = -0.4, p = 0.16). For HIV-1 treated patients, the viral loads were too low to detect so it was not possible to calculate the correlation. Elevated MFI levels of ZAP-70 molecules in CD4+ cells in HIV infected patients may be associated with an inability to further activate T-cells. PMID- 20578494 TI - Access to HIV testing for sex workers in Bangkok, Thailand: a high prevalence of HIV among street-based sex workers. AB - We offered voluntary counseling and testing (VCT) for HIV and syphilis to women attending three public sexually transmitted infection (STI) clinics in Bangkok, Thailand from May 2004 to June 2006. The testing was performed at either one of three STI clinics in Bangkok or at mobile VCT in the same area as the outreach activity. Six-hundred eighty-four women were tested. The HIV prevalences among the street-based sex workers, brothel-based sex workers and other women in these areas not reporting sex work who tested in the clinics were 45.8% (38/83), 4.2% (10/236) and 9.9% (28/284), respectively. The prevalences of syphilis in these groups were 13.3%, 2.1%, and 2.6%, respectively. Street-based sex work and longer duration of sex work were independent risk factors for HIV in-fection (p < 0.001 and p = 0.02, respectively). HIV and syphilis prevalences were 21.0% and 3.7% among 81 street-based sex workers accepting mobile VCT, The street-based sex workers in Bangkok had substantially higher HIV and syphilis prevalences than other sex workers. Street-based sex workers should be sampled during routine surveillance to obtain systematic information on disease preva-lence and risk behaviors in this group. PMID- 20578495 TI - Tuberculosis and MDR-TB in the northern emirates of United Arab Emirates: a 5 year study. AB - In this study, we describe the prevalence of TB and occurrence of multi-drug resistance tuberculosis (MDR-TB) in a major referral hospital belonging to the Ministry of Health in Sharjah, United Arab Emirates (UAE). A retrospective re view of the clinical and laboratory records of 1,810 suspected cases of TB was carried out between January 2004 and September 2008. The antimicrobial susceptibility patterns of each Mycobacterium tuberculosis isolate were analyzed. During the study period, 312 M. tuberculosis culture confirmed cases were recorded; 230 were males and 82 were females. The majority of TB cases (36%) were seen among expatriates from South and Southeast Asian countries. Fifty-one active TB cases (16%) were reported in native people (Emaratis) of the country. The peak age group was between 16 and 45 years. Among first-line antituberculosis drugs, resistance to isoniazid was the most common (21%), followed by streptomycin (14%). MDR-TB was found in 15 cases (4.8%). Although the prevalence of TB in UAE is fairly low, an increasing number of cultures confirmed TB and MDR-TB among native and expatriate patients, necessitating improved vigilance in case detection, effec-tive management and prevention of MDR and XDR-TB emergence in the country. PMID- 20578496 TI - Spectrum of melioidosis in the suburbs of Mangalore, S West Coast of India. AB - Melioidosis is an emerging infection in India. Seventeen cases of culture proven melioidosis are reported in this study. The isolation rate was high during the rainy season. Except one case, all the patients had diabetes mellitus as an underlying disease. Eleven patients improved with ceftazidime or combination therapy and maintenance therapy with doxycycline and Cotrimoxazole. The high prevalence of B. pseudomallei in this region is a matter for serious concern. PMID- 20578497 TI - Patterns of rhinosporidiosis in Sri Lanka: comparison with international data. AB - One hundred forty-three cases of rhinosporidiosis, confirmed by smear or biopsy, treated in two major General Hospitals in Sri Lanka over a 14 year period (1995 2009) were analyzed in regard to their epidemiological, clinical, clinicopathological, immunological and microbiological features. Regional variations in incidence, age and sex distribution, bathing history, and histopathology were seen. Lacustrine waters were the commonest probable source of infection (84%). Rivers were a source of Rhinosporidium seeberi in Sri Lanka (11%) and domestic well water was a probable source in 5%. The epidemiological features, clinical presentations and histopathology were similar to those in other series. The antirhinosporidial antibody (mean) titers were IgM--142.1 and IgG--178.5, compatible with rhinosporidiosis of long duration. Mantoux positivity to PPD was found in 65% of normal Sri Lankans, by only 35% of patients with rhinosporidiosis. No outbreaks have been reported in Sri Lanka or India. No animal cases of rhinosporidiosis have been reported in Sri Lanka, although rhinosporidiosis in animals has been repeatedly documented in India. PMID- 20578498 TI - Digital gangrene following a green pit viper bite. AB - In Hong Kong, the white-lipped green pit viper (Trimeresurus albolabris) accounts for the majority of venomous snake bites. In these patients, the cardinal features are local pain and swelling and mild coagulation abnormalities, but digital gangrene is uncommon. A 58-year-old woman was bitten on the left middle finger pulp by a white-lipped green pit viper. She developed local pain and swelling and coagulopathy, complicated by pulp tissue necrosis and digital gangrene of left middle finger. She fully recovered after amputation of the left middle finger at the mid portion. PMID- 20578499 TI - Venomous snake bites in Lao PDR: a retrospective study of 21 snakebite victims in a provincial hospital. AB - This is a retrospective case series report of 21 snakebite victims admitted to a provincial hospital 80 km north of the capital city Vientiane between January 2007 and June 2008. There were 13 Malayan Pit Viper (MPV) and 6 Green Pit Viper (GPV) bites. Two patients could not identify the snake, but developed severe coagulopathy and were therefore most likely bitten by a MPV or GPV. Seven of 13 patients bitten by the MPV and 3 of 6 patients with GPV bites developed a coagulopathy; 2 patients bitten by a MPV had severe local signs of envenomation. The supply of antivenom was limited, thus only 6 patients received this treatment, although it was indicated in 12. The treatment was effective and the INR was normal or less than 3 within 24 hours. No early side effects occurred after injection of monospecific antivenom obtained from the Thai Red Cross. Antivenom is not available in most hospitals of the country and the majority of snakebite victims are still treated by traditional healers in the villages. Training of medical doctors and health workers in the management of snakebites is urgently needed to improve the outcome of this neglected disease in Lao PDR. PMID- 20578500 TI - A statistical method for estimating under-reported incidence rates with application to child diarrhea in Thai provinces bordering Cambodia. AB - Diarrhea is a major health problem in Thailand, but reported data of disease incidence are known or suspected to be under-reported. This study aimed to develop a statistical model for estimating the annual incidence of hospital diarrhea cases among children under five years. Data regarding diarrhea patients 0-4 years old were collected for the National Notifiable Disease Surveillance (Report 506) about Thai provinces bordering Cambodia during 1999-2004 by the Ministry of Public Health. A log-linear regression model based on the prevailing seasonal-trend pattern was used for diarrhea incidence as a function of quarter, year and district, after imputing rates where under-reporting was evident, using populations obtained from the 2000 population census. The model also takes any spatial correlation between districts into account, using the generalized estimating equation (GEE) method. Diarrhea incidence had seasonal peaks in the first quarter (January to March) and the trend steadily increased from 1999 to 2004. Results from such studies can help health authorities develop prevention policies. PMID- 20578501 TI - Efficiency and cost-effectiveness of dyslipidemia screening methods among workers in Bangkok. AB - Dyslipidemia is now a worldwide health problem. Secondary prevention in the form of early detection of dyslipidemia and risk modification via drug and non-drug procedures, particularly among the high-risk group, is thus imperative. The objective of this study was to determine the sensitivity and specificity, cost, and cost-effectiveness of dyslipidemia screening methods which were proposed by the Royal Thai Medical Association (RTMA), the United States National Cholesterol Education Program (NCEP), British Hyperlipidemia Association (BHA), and our modified screening instrument (MSI). A cross-sectional descriptive study was conducted among 2,000 workers aged > or = 35 years taking annual health examination from a university hospital during July-September, 2008. Sensitivity and specificity of the screening methods were analyzed using the universal serum lipid testing as the gold standard. Their total and unit costs, and cost effectiveness were then calculated. Overall, the sensitivities for detecting any type of serum lipid abnormalities ranged between 29.9-99.4 %, while the specificities ranged between 0.5-74.1%. The total costs per 1,000 people screened ranged between THB 88,742 - 184,750. No screening method was obviously more cost effective when using the cost per case detected of the universal blood test as the reference. PMID- 20578502 TI - Psychosocial burden of abnormal pap smears among HIV-infected women at Chon Buri hospital, Thailand. AB - This retrospective case-control study assessed the psychological burden of abnormal Pap smears, and their prevalence and characteristics among HIV-infected women attending an HIV clinic. Women with positive (n = 73) and negative Pap smear results (n = 317) were assessed for psychosocial burden using 4 questionnaires: Psycho-Social Impact of Abnormal Pap Smears (PEAPS-Q), Hospital Anxiety and Depression Scale (HADS), Work Productivity and Impairment (WPAI) and the EURO-Qol Thermometer. The prevalence of pre-cervical cancer lesions in HIV infected woman was 17.5% (ASCUS 2.9%, LSIL 3.8%, HSIL 7.4%, SCC 1.7%, and atypical glandular cells including adenocarcinoma 1.7%). HIV infected women with abnormal Pap smears showed higher anxiety levels on the HADS questionnaire (p = 0.015); this had a significant effect on regular daily activities (p = 0.009) per the WPAI questionnaire compared to HIV positive women with normal Pap smear. Ever married HIV infected woman with an abnormal Pap smear had a significantly lower psychosocial burden using the PEAPS-Q questionnaire (p < 0.001). After adjusting for age and duration since last Pap smear, the education level of the patient was a strong predictor for anxiety. Patients, with a college education had significantly lower anxiety (p = 0.001, 95% CI -5.74 to -1.37) than those with lower or higher education. Women with HSIL were more anxious (p = 0.014, 95% CI 0.49 -4.39) than those with low grade or normal lesions. PMID- 20578503 TI - The lifeline express--a mobile ear clinic for rural India. AB - The objectives of this study were to review the application and feasibility of providing screening, diagnosis, medical and surgical treatment for patients with ear discharge by setting a mobile hospital in rural India. The study was retrospective. The study involved collection of data from 1992 to 2005 from patients with ear diseases. The number of patients operated on for ear conditions and the distribution of free hearing aids were also recorded. Data regarding length of postoperative stay, complications and graft failure rates was collected from local medical centers and analyzed. Out of 304,321 patients, 4,426 were operated on for ear diseases, mostly ear perforations, grommet insertions and cholesteatoma surgeries. A total of 11,913 audiometric evaluations were done and 9,045 hearing aids were distributed. An overall success rate of 78.8% was achieved for achieving a dry ear and approximately 60% reported significant improvement in audiometric thresholds. PMID- 20578504 TI - Some views about the high cost of medical care in China. AB - Since China began its reform and opened up to the outside world, medical technology and treatment have improved greatly, but the cost of medical care has increased, causing an increasing burden on the Chinese people. We attempted to find reasons for the high cost medical treatment. These included: 1. the high cost of new drugs and high medicine rebates; 2. the bonus distribution system in the hospitals; and 3. over use. We provides some suggestions to control these high costs, such as controlling the price of new drugs, controlling the medical examination fee and punishment for causing high cost. PMID- 20578505 TI - Effects of fluoride dentifrice on remineralization of demineralized primary enamel. AB - This study was performed to compare the remineralizing effects of various concentrations of fluoride containing dentifrices against artificial demineralization of primary enamel. One hundred twenty primary incisors were partly covered with a nail varnish, leaving a 1 x 1 mm window, then placed in demineralizing solution for 96 hours to produce artificial carious lesions 60-100 microm in depth. They were assigned to 8 groups (A to H; n = 15). Groups A-D were exposed to a half pea-sized portion of dentifrice (0.16 g) and groups E-H were exposed to a pea-sized portion of dentifrice (0.32 g), both groups with fluoride concentrations of 0, 250, 500 and 1,000 ppm. The pH-cycling method was carried out for 7 days, then the teeth were cut through the lesions and examined under a polarized light microscope; photographs were taken and analyzed. Lesion depth was measured using a computerized method using the Image-Pro Plus Program. The results were analyzed using the One way ANOVA and LSD tests. The mean lesion depth in the 2 non-fluoridated control groups (A and E) were significantly deeper than in the fluoridated groups. There were no differences found between the half pea-sized and pea-sized dentifrice. PMID- 20578506 TI - Green tea extract supplement inhibition of HMGB1 release in rats exposed to cigarette smoke. AB - Tobacco-smoke exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea has been reported to have anti-release properties against various pro-inflammatory cytokines. To determine the effects of green tea extract (GTE) on serum high mobility group box-1 (HMGB1) levels in rats exposed to cigarette smoke (CS), we divided rats into 4 treatment groups: (1) CS only, (2) dietary supplement with GTE (3 mg/d) and CS (GCS1), (3) dietary supplement with GTE (4.5 mg/d) and CS (GCS2) and (4) a control group. HMGB1 and cotinine serum levels were analyzed by ELISA. The average serum HMGB1 level in the CS group was significantly higher than the other groups (p < 0.01), indicating the release of HMGB1 into the blood was stimulated by CS exposure, while GTE consumption suppressed HMGB1 levels. Rats exposed to CS had an average serum cotinine level of 37 ng/ml, indicating tobacco related compounds were present in the rats' blood. However, treatment with GTE did not reduce cotinine levels in all groups. Cotinine stimulated HMGB1 secretion in a dose- and time-dependent manner, and HMGB1 levels were suppressed by GTE in murine macrophage cell lines. Our results show GTE supplementation may offer beneficial systemic effects and suppress HMGB1 by protecting against cell inflammation. PMID- 20578507 TI - Detection of Toxoplasma gondii DNA by PCR following microwave treatment of serum and whole blood. AB - Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate early diagnosis of toxoplasmosis in different groups of patients. We evaluated this approach in 42 patients presenting with ocular or psychotic diseases by comparing the sensitivity and specificity of PCR after heat treatment using a microwave oven with a standard genomic DNA extraction method for paired serum and whole blood samples. The presence of serum IgM and IgG antibodies against T. gondii was detected using a standard commercial enzyme linked immunosorbent assay and enzyme immunoassay for IgG avidity test. Of 42 whole blood samples, PCR after microwave treatment was positive in 8 samples with a sensitivity of 73% and specificity of 100% compared to 11 samples positive by the extraction method. Although none of 42 sera samples was PCR positive by the extraction method, 7 specimens were positive after microwave treatment. This is the first study to use a microwave heat treatment, which is simple, rapid and a promising alternative method, in detecting small amounts of T. gondii DNA in human blood. Furthermore, irradiation of blood samples with microwaves allows incorporation of PCR into a practical tool for routine clinical assessment of patients with Toxoplasma infection. PMID- 20578508 TI - Malaria perceptions and practices in Bhutan. AB - The aim of this study was to understand the perceptions and practices concerning malaria in Bhutan so as to initiate a basis for further study. This study was conducted from July to August 2007 by using focused group discussions with health workers, community members and village health workers. Our study revealed that certain portions of the fever patients in the community seek alternative remedies within their communities before availing modern treatment facilities. The main factors causing delay reporting to the health facility were long distance to the health facility, socio-cultural and religious practices, financial, lack of manpower, and lack of knowledge, cultural norms and quality of services from health facilities. It can be concluded that there is still a major problem seeking early diagnosis and prompt treatment by a fever patient. In order to overcome the problems and achieve the program goals, further studies are needed to generate evidences in developing interventions to promote the early diagnosis and prompt therapy. PMID- 20578509 TI - Improved sensitivity of PCR amplification of glutamate dehydrogenase gene for detection and genotyping of Giardia duodenalis in stool specimen. AB - A modified set of primers was developed to increase the sensitivity of nested PCR amplification of glutamate dehydrogenase (gdh) gene to detect and genotype Giardia duodenalis cysts in stool specimens. This modified set of primers had a significantly higher sensitivity (82%) than that of a previously published PCR primer set (53%). PMID- 20578510 TI - Size and charge antigens of Dirofilaria immitis adult worm for IgG-ELISA diagnosis of bancroftian filariasis. AB - We used Dirofilaria immitis adult worm antigens to develop an IgG-ELISA, then used this to evaluate 30 serum samples of patients with proven Wuchereria bancrofti infection, 131 samples of patients with other parasitic diseases and 30 serum samples of healthy controls. The D. immitis antigen was prepared using two methods: Sephacryl S-200 chromatography and iso-electric focusing with a Rotofor cell. This was done to determine the best method for diagnosing W. bancrofti filariasis. Before fractionation, crude male D. immitis antigen yielded 100% sensitivity and 60.8% specificity, and crude female antigen yielded 80% sensitivity and 52.8% specificity, respectively, to detect W. bancrofti infection. After gel filtration chromatography, the male D. immitis antigen, called MP1, yielded 100% sensitivity and 95% specificity, and female D. immitis antigen, called FmP1, gave 100% sensitivity and 59.6% specificity, to detect W. bancrofti infection. Using iso-electric-focusing, both male and female crude D. immitis antigens (Iso-MF and Iso-FmF, respectively) were separated mechanically into 20 iso-fractions (F1-F20) each. By preliminary screening with ELISA, using pooled positive and negative sera, Iso-MF10, pH 7.5, and Iso-FmF14, pH 7.6, were selected. Iso-MF10 gave 100% sensitivity and 96.9% specificity, and Iso-FmF14 gave 100% sensitivity and 64% specificity. In the study, Og4C3-ELISA, for the detection of circulating filarial antigen, was also used to analyze these serum samples, it gave 87.6% sensitivity and 99.4% specificity to detect W. bancrofti infection. Male D. immitis antigens, MP1 and Iso-MF10, gave high sensitivity and specificity, and appear to be the best choices for use in an ELISA to diagnose bancroftian filariasis. PMID- 20578512 TI - Prevalence and risk factors for pinworm infection in the kindergarten of Thammasat University, Thailand. AB - We studied the prevalence and risk factors for pinworm infection in children attending the kindergarten of Thammasat University, Pathum Thani, Thailand, using the Scotch-tape technique. Slides were examined by a standard light microscope; 20% of negative slides were reexamined for quality control. Symptoms and risk factor data were collected using a structured questionnaire. Three hundred thirty children age 3 to 6 years old were sampled (males=159). Sixty-five (19.7%) had symptoms consistent with pinworm infection. No pinworm eggs were detected. Most parents (73%) had a good socioeconomic status and 64% were university graduates. Pinworm infection may be uncommon in urban Thailand. PMID- 20578511 TI - An enzyme-linked immunosorbent assay as screening tool for human intestinal capillariasis. AB - Human intestinal capillariasis caused by Capillaria philippinensis is characterized by chronic diarrhea which may lead to death if left untreated. The mortality is highest among patients who are negative by conventional stool examination. Therefore this study explored the application of an enzyme-linked immunosorbent assay (ELISA) as a screening test for human intestinal capillariasis. The ELISA was developed using Trichinella spiralis soluble antigen for the detection of antibodies against C. philippinensis. A cut-off level at the upper 99% limit of the absorbance values of the healthy controls was established for positivity. All intestinal capillariasis sera showed positive ELISA, demonstrating 100% sensitivity, while all healthy control sera gave absorbance values below the cut-off level, resulting in 100% specificity. The ELISA was also positive with 75% of trichinellosis, 13.9% of strongyloidiasis, 9.1% of trichuriasis, and 4.2% of opisthorchiasis sera. The ELISA and immunoblot were in agreement in 91.1% of the sera tested. It was suggested that the here-presented ELISA is capable to detect intestinal capillariasis cases in endemic areas whose coproscopy is negative for worm eggs, larvae or adults. PMID- 20578513 TI - Combination larvicidal action of Solanum xanthocarpum extract and certain synthetic insecticides against filarial vector, Culex quinquefasciatus (SAY). AB - The combination activities of temephos, fenthion and petroleum ether extract of Solanum xanthocarpum were observed for their larvicidal activities against Culex quinquefasciatus. The combination of temephos and S. xanthocarpum was studied at ratios of 1:1, 1:2, and 1:4. Similar ratios were also used for the combination of fenthion and S. xanthocarpum. The temephos/plant extract combination acted antagonistically. The combination of fenthion and plant extract acted synergistically against the target organisms at a ratio of 1:1, which showed the best results of: LC50 0.0144 and 0.0056 ppm and LC90 0.0958 and 0.0209 ppm at 24 and 48 hours, respectively. The present study will be helpful in developing a commercial formulation for effective vector management. PMID- 20578514 TI - Effect of crude extract of Solanum xanthocarpum against snails and mosquito larvae. AB - The ethanolic crude extract from Solanum xanthocarpum was investigated for its molluscicidal activity against Biomphalaria glabrata, the snail vector of Schistosoma mansoni, and Indoplanorbis exustus, the snail vector of intestinal echinostomiasis and Schistosoma spindale, together with the larvicidal activity against the larvae of Aedes aegypti, mosquito vector of dengue hemorrhagic fever and Culex quinquefasciatus, the mosquito vector of urban bancroftian filariasis. The bioassays were carried out following the methods recommended by the World Health Organization. For molluscicidal activity, the LC50 against Bi. glabrata and I. exustus were reported at 163.85 and 198.00 mg/l while the LC90 were 219.33 and 236.80 mg/l, respectively. Regarding mosquito larvicidal activity, the LC50 against the larvae of Ae. aegypti and Cx. quinquefasciatus were 788.10 and 573.20 mg/l, while the LC90 were 1288.91 and 1066.93 mg/l, respectively. These results suggest a preparation of ingredients from this plant may be used as a biological larvicide for these vectors in the field. PMID- 20578516 TI - Clinical factors associated with mortality in dengue infection at a tertiary care center. AB - We conducted a cross-sectional study to investigate the clinical factors associated with mortality in patients with dengue viral infection at a tertiary care center over a 3 year period. Six hundred ninety-nine patients with a clinical diagnosis of dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) during the study period were included in the study. Data were collected with a predesigned form comprised of demographics, duration of fever, associated symptoms, diagnosis of DF, DHF and DSS, and laboratory parameters [complete blood count, coagulation tests, creatinine, serum glutamic pyruvic transaminase (SGPT)]; dengue IgM was checked in all patients by ELISA. Outcomes (survival/mortality) and complications were recorded. Mortality was the primary outcome measure. DF constituted 86.4% (604), DHF constituted 11.6% (81) and DSS constituted 2% (14) of patients. The mortality rate was 2.7% (19). The mean white blood cell count in those who died was 13.3, in those who survived was 5.3, the difference was significant (p = 0.02). The mean BUN in those who died was 33.2, those who survived was 13.8, (p = 0.007). The mean bicarbonate level in those who died was 17.1, those who survived was 18.5 (p < 0.001). Mean activated partial thromboplastin time in those who died was 56.8, those who survived was 36.8 (p = 0.01). The mean SGPT in those who died was 802, those who survived was 176 (p = 0.01). Those who died were significantly (p < 0.001) more likely to have severe hepatitis (63%) than those who survived (13.8%). On multivariate logistic regression analysis, having an SGPT >300 mg/dl, bleeding, an altered mental status and shock at presentation were all significantly associated with mortality in patients with dengue virus infection (p = 0.008, p < 0.001, p < 0.001, p < 0.001, respectively). PMID- 20578515 TI - Laboratory predictors of dengue shock syndrome during the febrile stage. AB - The clinical manifestations of dengue hemorrhagic fever (DHF) consist of three successive stages: febrile, toxic and convalescent. The toxic stage is the critical period, which may manifestas circulatory disturbance or even profound shock in some patients. We attempted to determine predictors for the risk of dengue shock syndrome (DSS) during the febrile stage. One hundred one children with acute febrile illness were enrolled in the study, with a mean age of 11 years old. The diagnosis included dengue fever (DF) 21 cases, DHF grade I 30 cases, DHF grade II 33 cases, DHF grades III and IV 10 cases; children with other febrile illnesses (OFI) 7 cases were used as controls. Complete blood counts, coagulation tests, von Willebrand factor antigens (VWF:Ag) and ristocetin cofactor activity (VWF:Rcof) were determined daily during hospitalization and 2-4 weeks after discharge from the hospital. The results revealed any one of the following abnormal laboratory findings during the febrile stage served as a predictor for risk of DSS: increase in hematocrit > 25%, a platelet count < 40,000/microl, an activated partial thromboplastin time >44 seconds, a prothrombin time >14 seconds, a thrombin time >16 seconds or a VWF:Ag or VWF:Rcof > 210%. The relative risk ranged from 4.8 to 10.9. Simple laboratory investigations with complete blood count, coagulation test or the more sophisticated von Willebrand factor, are helpful in predicting the risk for DSS during the febrile stage. PMID- 20578517 TI - Molecular characterization of human group A rotavirus from stool samples in young children with diarrhea in Indonesia. AB - Detection and genotyping of group A rotavirus strains from stool samples in young children with diarrhea in Indonesia were examined using reverse transcription nested multiplex PCR. Of 421 stool specimens, 257 samples was rotavirus positive. G1 type was the most common G-type (54%), followed by G2 (6%) and G9 (3%). P[8] was the most common P-type (39%), followed by P[6] (19%), P[4] (10%) and P[11] 1%. Eighteen percent of the samples had mixed G genotype infection and 5% had mixed P genotype infection. The prevalence of G-P combination type was genotype G1P[8] (24%), followed by G1P[6] (7%), G2P[4] (3%), and G1P[4] (2%). A total of 118 specimens could not be assigned as a G and/or P type suggesting the presence of new circulating genotypes in Indonesia. PMID- 20578518 TI - Sustained appearance of drug resistance-associated mutations in HIV-1 CRF01_AE protease and reverse transcriptase derived from protease inhibitor-naive Thai patients. AB - Previous studies revealed that HIV-1 CRF01_AE viruses derived from antiretroviral drug-naive Thai patients contained several protease (PR) inhibitor (PI) resistance-associated mutations. In this report, we examined the sustained appearance of drug resistance-associated mutations in CRF01_AE PR and reverse transcriptase (RT). Peripheral blood samples were collected every 3 months from April 2008 to April 2009 from 39 HIV-1-infected Thai patients, including 17 drug naive and 22 RT inhibitors (RTIs)-treated individuals, and polymerase chain reaction-mediated-amplification and sequencing analysis of the viral genome encoding PR and RT were performed. We successfully analyzed the deduced amino acid sequence of CRF01_AE PR and RT derived from samples continuously collected from 15 drug-naive and 20 RTIs-treated patients. Drug resistance-associated mutations were continuously detected in CRF01_AE PR derived from most patients. The continuous appearance of such PR mutations was observed not only in the proviral DNA genome derived from peripheral blood mononuclear cells, but also in the viral RNA genome of plasma virus. In contrast, RTI resistance-associated mutations were only sporadically detected in samples derived from drug-naive and RTIs-treated patients, except for the continuous appearance of two mutations in samples derived from two drug-naive patients. Our results demonstrate that many PI resistance-associated mutations and only a few RTI resistance-associated mutations continuously appear in CRF01_AE viruses derived from PI-naive patients residing in northern Thailand. PMID- 20578519 TI - HIV infection and mental health of "money boys": a pilot study in Shandong Province, China. AB - A pilot study was conducted in eight cities of Shandong Province, China to examine the seroprevalence of HIV and syphilis infection, and the mental health of "money boys" who were recruited by respondent-driven sampling and interviewed using a semi-structured questionnaire. The prevalence of the HIV-positive among money boys was 5.1%. Factors associated with the infection were having sex with women in the past 6 months (p < 0.05) and suffering STD-like symptoms (p < 0.01). The prevalence of syphilis was 10.2%. There were 77.2% participants engaged in such an occupation for economic survival. The prevalence of anxiety and depression among money boys was 46.6% and 68.1%, respectively. Heterosexual money boys were more likely to suffer from such mental symptoms. This study revealed the urgent need for interventions for HIV/AIDS control, together with mental counseling, targeting this vulnerable population. PMID- 20578520 TI - Simultaneous determination of stavudine and lamivudine in human plasma by high performance liquid chromatography and its application to a bioavailability study. AB - A high performance liquid chromatographic method with UV detection was developed and validated for simultaneous determination of stavudine and lamivudine in human plasma using solid-phase extraction for sample clean-up. Zidovudine was used as an internal standard. Separation was performed on a C18 column by gradient elution with a mobile phase of 10 mM acetate buffer pH 6.5 and acetonitrile. The UV detection was set at 265 nm. The method proved to be specific, accurate, precise and linear over the concentration ranges of 50-3000 ng/ml for stavudine and 50-5000 ng/ml for lamivudine with correlation coefficients always > 0.996 for both drugs. The intra-day and inter-day precision and accuracy were less than 9.2% for both analytes. The absolute recoveries of both compounds ranged from 93.3 to 97.5%. The method was successfully applied to a bioavailability study of a combined tablet formulation containing 30 mg of stavudine and 150 mg of lamivudine compared with each reference formulation concurrently administered in 26 healthy Thai male volunteers. PMID- 20578521 TI - Tuberculosis: an eight year (2000-2007) retrospective study at the University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. AB - This was an eight year (2000-2007) retrospective study of tuberculosis in patients admitted to the UMMC. A total of 131 cases were analyzed. Malays constituted the most cases, (43%), followed by Chinese (22%), Indians (17%) and others (18%). The majority of cases were within the 21-60 year old age group, which constituted 69.5% of the total. Males were more commonly affected (65%). Most cases were reported among Malaysians (83%). The majority of patients were unemployed (39%), followed by housewives (10%), laborers (9%), students (8%), shop assistants (7%), and other occupations (27%). The most common presenting complaints were prolonged productive cough, night sweats, fever, anorexia, weight loss (57%), hemoptysis (34%), and undifferentiated symptoms, such as prolonged diarrhea and dysphagia (9%). Sputum was positive for acid-fast bacilli (AFB) in 89%, but only 69% of cases had abnormal chest radiographs. The majority of patients (65%) developed no complications. The most common complications were pleural effusion, pneumothorax and pulmonary fibrosis. The majority of patients (82%) suffered either from diabetes mellitus, hypertension, ischemic heart disease or all 3 conditions. Regarding risk factors for tuberculosis, two were HIV positive and two were intravenous drug users. The majority of the patients (85%) did not complain of any side effects from their anti-tuberculosis treatment. Among those who did complain of side effects, the most common were nausea and vomiting (41%), drug induced hepatitis (37%), blurring of vision (11%) and skin rashes (11%). Two cases of death were reported. PMID- 20578522 TI - NRAMP1/SLC11A1 gene polymorphisms and host susceptibility to Mycobacterium tuberculosis and M. leprae in South Sulawesi, Indonesia. AB - Genetic host factor may play an important role in controlling mycobacterial infections such as tuberculosis and leprosy. Natural resistance associated macrophage protein1 (Nramp1, alias Slc11a1) gene has been suggested to an associated gene of the host susceptibility to mycobacterium infection. To determine the association of Nramp1/Slc11a1 with tuberculosis and leprosy, we analyzed using polymerase chain reaction restriction fragment length polymorphisms three variants (D543N, 3'UTR and INT4) of Nramp1/Slc11a1 gene in 58 tuberculosis patients (mean age, 34.0 +/- 13.1), 42 leprosy patients (mean age, 35.0 +/- 14.3) and 198 healthy controls (mean age, 32.0 +/- 12.9) from South Sulawesi, Indonesia. We observed an association of INT4 polymorphism with paucibacillary type of leprosy (p = 0.032, 1df, OR = 2.975, CI = 1.057-8.373), but not to multibacillary type (p = 0.173, 1df, OR = 2.248, CI = 0.682-7.404). No significant association was found in the three variants with tuberculosis in this population. PMID- 20578523 TI - Burkholderia thailandensis whole cell antigen cross-reacts with B. pseudomallei antibodies from patients with melioidosis in an immunofluorescent assay. AB - An immunofluorescent assay (IFAT) using whole cell antigen derived from Burkholderia thailandensis used for detection of total antibodies to Burkholderia pseudomallei, was found to compare favorably with a previous published report on a B. pseudomallei IFAT assay. At a 1:20 cut-off titer, the assay had high sensitivity (98.9%) and satisfactory specificity (92.3%), when tested against sera from 94 patients suspected of melioidosis. Sera from 12 patients with culture proven melioidosis gave absolute concordance with the 2 test antigens. No sera from 50 blood donors had a titer of > or =20. Cross-reactivity with patients' sera positive for Chlamydia, Mycoplasma, Legionella and typhoid was not observed, except for 3 sera from typhus patients and one from a patient with leptospirosis. The major advantage of this assay is that the cultivation and preparation of B. thailandensis as antigen can be carried out in any laboratory with basic microbiological set-up. The serodiagnosis of melioidosis can be made safe for medical laboratory personnel, particularly in B. pseudomallei endemic regions. PMID- 20578524 TI - Melioidosis in southern India: epidemiological and clinical profile. AB - Melioidosis, which is mainly prevalent in Thailand and Australia, has shown an increasing trend in India in the last few years. We carried out a retrospective study of 25 culture-proven adult cases of melioidosis who were admitted to a tertiary care hospital in southern India during June 2001 to September 2007. There was a six-fold increase in the number of cases in 2006 and 2007 as compared to 2001. Diabetes mellitus was the predisposing factor in 68% of cases, followed by alcoholism (28%). The clinical presentations were fever (80%), pneumonia and/or pleural effusion (48%), hepatomegaly (56%), joint involvement, and/or osteomyelitis (48%), splenomegaly (40%), splenic abscess (24%) and septicemia (28%). The organism, Burkholderia pseudomallei, was sensitive to co-amoxiclav, cotrimoxazole, ceftazidime, and carbapenem. The study suggests that melioidosis is an emerging infectious disease in the southwestern coastal belt of India, and it is likely to happen at much higher incidence. PMID- 20578525 TI - Pulsed field gel electrophoresis analysis of Vibrio cholerae isolates in southern Thailand. AB - Forty isolates of V. cholorae O1, O139 and non-O1/non-O139 collected from outbreaks in Songkhla and Phuket Provinces of southern Thailand during 1999-2001 and sporadic cases from different regions of Thailand during 1993-2002 were characterized using pulsed field gel electrophoresis (PFGE). Digestion of chromosomal DNA of the V cholerae isolates with restriction endonuclease NotI, followed by PFGE, generated 10 distinct restriction endonuclease analysis patterns consisting of 8 to 13 bands, ranging in size from 78 to 394 kb. PFGE patterns of O1 Inaba strains from the outbreak in Songkhla were identical (P1) except one isolate (P3). The O1 Inaba outbreak strains from Phuket in the same period belonged to P2 pattern, whereas the O1 Ogawa strain from the outbreak in Phuket isolated in 1999 was of P7 pattern. These patterns of O1 Inaba and Ogawa strains were slightly different suggesting that the isolates were epidemiologically related and therefore the outbreaks were likely due to the same V cholerae clone. Isolates of V cholerae O1 Inaba from sporadic cases in the neighboring area (e.g., Pattani Province) in a similar period of time of the outbreak in Songkhla Province had very similar patterns, with only one single band different from those of the outbreak isolates. This indicates that the Inaba strains isolated from Songkhla Province during the 2001 cholera outbreak belonging to P1 pattern had not spread to other regions in 2001 and 2002. On the otherhand, the sporadic isolates collected from other regions of Thailand were quite distinct from the outbreak isolates in Songkhla Province, especially those from Chaiyaphum and Chaing Mai Provinces, which belonged to P5 and P6 pattern, respectively. Isolates of V cholerae O139 and non-O1/non-O139 gave different patterns from that of V. cholerae O1. This study shows that the PFGE technique is markedly advantageous in distinguishing strains of V cholerae isolates leading to insightful detailed charateristics of these isolates in Thailand. PMID- 20578526 TI - Shigella-associated diarrhea in children in South Jakarta, Indonesia. AB - A surveillance of Shigella infections was conducted on 612 children aged 0-12 years-old presenting with diarrhea to Mampang and Tebet Community Health Centers in South Jakarta, Indonesia, during February 2005 through September 2007. Shigella was isolated from 9.3% of diarrhea patients in the health centers. S.flexneri which was found in 5.9% of patients, and was the most frequent species isolated, comprising 63.2% (36/57) of all Shigella species isolated. Shigella species were found significantly more often among children over 2 years old, and the rate of isolation increased with age. Stool with mucus and/or blood were the main characteristics of Shigella infection in these patients. Antibiotic multi resistance was found in S. flexneri and S. boydii strains, in particular to ampicillin, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole. None of the Shigella species showed resistance to nalidixic acid, norfloxacin, ciprofloxacin, or ceftriaxone PMID- 20578527 TI - Detection of Salmonella invA gene in shrimp enrichment culture by polymerase chain reaction. AB - Contamination of seafood with salmonellae is a major public health concern. Detection of Salmonella by standard culture methods is time consuming. In this study, an enrichment culture step prior to polymerase chain reaction (PCR) was applied to detect 284 bp fragment of Salmonella invA in comparison with the conventional culture method in 100 shrimp samples collected from four different shrimp farms and fresh food markets around Bangkok. Samples were pre-enriched in non-selective lactose broth (LB) and selective tetrathionate broth (TTB). PCR detection limit was 10 pg and 10(4) cfu/ml of viable salmonellae with 100% specificity. PCR assay detected 19 different Salmonella serovars belonging to 8 serogroups (B, C1, C2-C3, D1, E1, E4 and K) commonly found in clinical and environmental samples in Thailand. The detection rate of PCR following TTB enrichment (24%) was higher than conventional culture method (19%). PCR following TTB, but not in LB enrichment allowed salmonella detection with 84% sensitivity, 90% specificity and 89% accuracy. Shrimp samples collected from fresh food markets had higher levels of contaminated salmonellae than those from shrimp farms. The results indicated that incorporation of an enrichment step prior to PCR has the potential to be applied for detection of naturally contaminated salmonellae in food, environment and clinical samples. PMID- 20578528 TI - Genetic stability and worldwide dissemination of integron insert encoding trimethoprim resistance. AB - A hospital-based surveillance study of class 1 integron-positive Acinetobacter isolates in the Urals and Siberia (Russia) demonstrated that dihydrofolate reductase gene (dfrA5) was located in a functional gene cassette insertion driven from a promoter of a weak type. This insertion is an example of the integron associated trimethoprim resistance disseminated worldwide from the free-living animals to human. Despite the long-term persistence as an integron insert any loss or modifications in the nucleotide sequence especially at attC site was not observed. Nucleotide sequence previously referred as a weak type promoter may be considered as a wild-type configuration of an integron promoter region. PMID- 20578529 TI - Fungal rhinosinusitis: a retrospective analysis of clinicopathologic features and treatment outcomes at Ramathibodi Hospital. AB - The objective of this study was to determine the clinicopathologic findings of invasive and non-invasive fungal rhinosinusitis and to compare the features of the two diseases. The medical records of patients with invasive and noninvasive fungal rhinosinusitis at Ramathibodi Hospital between July 1999 and June 2009 were analyzed. The criterion for the diagnosis of fungal rhinosinusitis was the evidence of fungal elements from histopathologic section on sinonasal specimens. The age, gender, clinical manifestations, duration of symptoms, associated diseases, laboratory data, results of mycotic culture and treatment outcomes were analyzed. The relationship between fungal rhinosinusitis and patient characteristics as well as clinical presentations were assessed. The fungus attributable mortality rate was determined. The study included 43 cases of invasive fungal rhinosinusitis and 68 cases of non-invasive fungal rhinosinusitis. There were 44 male, and 67 female patients. The mean age at diagnosis was 54.6 years (range: 5 to 86 years). A total of 70 (63.1%) were attributed to aspergillosis, 8 (7.2%) to candidiasis, 6 (5.4%) to zygomycosis, 4 (3.6%) to phaeohyphomycosis, 1 (0.9%) to pseudallescheriasis, 1 (0.9%) to entomophthoromycosis and 21 (18.9%) to nonspecific fungi. Cultures from sinonasal tissues were positive for fungus in 37 of 87 cases (42.5%). The clinical presentations of fungal rhinosinusitis included nasal stuffiness (27.9%), nasal discharge (27.9%), facial pain (27.9%), fever (24.3%) and headache (19.8%). One fifth of cases had an underlying hematologic malignancy. Invasive fungal rhinosinusitis was significantly associated with hematologic malignancy and neutropenia. Fungus-attributable mortality rate was 44.2% in invasive fungal rhinosinusitis. Early antifungal therapy and surgical drainage were associated with a survival advantage. PMID- 20578530 TI - Evaluation of an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Hib-conjugate combined vaccine (Pentaxim) at 2, 4, and 6 months of age plus hepatitis B vaccine at birth, 2, and 6 months of age in infants in Thailand. AB - The objective of this study was to evaluate the immunogenicity and safety of a pentavalent vaccine (Pentaxim) containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Hib polysaccharide-conjugate (DTaP IPV//PRP-T) antigens, in Thai children. One hundred eighty-six infants who had received a hepatitis B vaccine at birth were given a pentavalent vaccine at 2, 4 and 6 months of age and a hepatitis B vaccine concomitantly at 2 and 6 months of age. Immunogenicity was high for each vaccine antigen. The study vaccine was well tolerated and side effects were few. After the third dose, 100% of subjects had an anti-PRP > or = 0.15 microg/ml and 96.5% > or = 1.0 microg/ml; the anti-PRP GMT was 9.53 microg/ml. Seroprotective rates for diphtheria and tetanus (> or = 0.01 IU/ml) were 99.4% and 100%, respectively, and 100% for all three poliovirus types (> or = 8 1/dil U). The vaccine response rates to pertussis antigens (a 4 fold increase in antibody titer were 94.1% for PT and 93.0% for FHA. The DTaP IPV//PRP-T vaccine given at 2, 4 and 6 months of age concomitantly with a monovalent hepatitis B vaccine, was well tolerated and highly immunogenic for primary immunization of infants in Thailand. PMID- 20578531 TI - Prevalence of sexually transmitted infections and sexual risk behavior among female sex workers in nine provinces in Indonesia, 2005. AB - The objective of this study was to assess the sexually transmitted infection (STI) prevalence and sexual risk behavior among female sex workers (FSWs) in Indonesia. This cross-sectional 2005 study involved 2500 FSWs in nine provinces in Indonesia. Informed consent was obtained; behavioral and clinical data were collected. Specimens were collected for STI testing, endocervical swabs were tested for Chlamydia trachomatis and Neisseria gonorrhoeae (PCR), vaginal smears were cultured to detect Trichomonas vaginalis and sera were tested for syphilis (RPR and TPHA). The prevalence of chlamydial infection was 43.5%, gonorrhea 28.6%, trichomoniasis 15.1%, and syphilis 8.7%; the prevalence of any STI was 64.0%. Inconsistent condom use, younger age, and higher number of clients were independent risk factors for the presence of gonorrhea/chlamydia. Inconsistent condom use was common (73.2%); starting sex work at younger age, and higher number of clients were independent risk factors. Vaginal douching was reported by 89.6% of FSWs; no association with gonorrhea/chlamydial infection was found. This study identified a high STI prevalence and low consistent condom use among FSWs in Indonesia. This will need to be addressed to prevent further spread of infections, including HIV. PMID- 20578532 TI - Comparison of efficacies between live and killed probiotics in children with lactose malabsorption. AB - The objective of this study was to determine the efficacy of live and killed probiotics to decrease the presence of hydrogen using the breath hydrogen test (BHT). This pretest-posttest control group design single blinded randomized study was performed in 5 government elementary schools in Tuminting subdistrict, Manado, Indonesia from March to May 2008. The study for inclusion as subjects consisted of healthy 10-12 year old children with heights and weights within normal limits using the Centers for Disease Control (CDC) criteria whose BHT was 220 parts per million (ppm), indicating lactose malabsorption. One hundred thirty children were screened, 86 met criteria, 43 children were randomized into two groups. Thirty-nine children who were given live probiotic and 40 children who were given killed probiotic completed the study. There was a significant difference when comparing the BHT results before and 120 minutes after giving probiotic for the children taking both the live and the killed probiotic (p < 0.001). When the children taking the live and killed probiotics were compared, there was no difference in the BHT at 120 minutes of probiotic (p = 0.453) by t test. The administration of live or killed probiotic for 2 weeks can decrease the results of a BHT in children with lactose malabsorption. No adverse reactions attributable to treatment were noted. PMID- 20578533 TI - Anti-proliferative and antioxidative activities of Thai noni/Yor (Morinda citrifolia Linn.) leaf extract. AB - In this study the leaves of the Thai noni/Yor, (Morinda citrifolia Linn.) were extracted by several methods and evaluated against human cancer cell lines: KB (human epidermoid carcinoma), HeLa (human cervical carcinoma), MCF-7 (human breast carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines as well as a Vero (African green monkey kidney) cell line, employing the MTT colorimetric method, comparing it to damnacanthal, rutin, and scopoletin. The dichloromethane extract of the fresh leaf showed a better inhibitory effect against KB and HeLa cells with IC50 values of 21.67 and 68.50 microg/ml, respectively. The dichloromethane extract of dried leaves revealed cytotoxicity against the KB cell line with an IC50 value of 39.00 microg/ml. Other extracts, as well as rutin and scopoletin, showed reduced anti-proliferative effects on all cancer cell lines (IC50 103 to over 600 microg/ml). Interestingly, the damnacanthal had potent cytotoxicity against all cancer cell lines and Vero cell lines. These results suggest Thai noni extracts may be safer than the pure compounds, due to their higher safety ratios, which is a good indicator for possible cancer treatment. Several non-aqueous extracts from the leaves showed antioxidant properties, giving IC50 values of 0.20-0.35 mg/ml. It can be concluded the leaves of M. citrifolia may have benefit as a food supplement for chemoprevention against epidermoid and cervical cancers. PMID- 20578534 TI - Acute effect of a single high-fat meal on forearm blood flow, blood pressure and heart rate in healthy male Asians and Caucasians: a pilot study. AB - Research has shown that ingestion of a single high-fat (HF) meal causes postprandial lipemia and produces a reduced brachial artery blood flow response to vascular occlusion in Caucasians. However, the forearm BF response to occlusion in Caucasian and Asian populations after a single HF meal has not been compared. Eleven healthy male Asians, mean age 26.4 (+/- 4.2) years, height 174.2 (+/- 7.4) cm, and weight 73.8 (+/- 5.7) kg and eight Caucasians, mean age 26.8 (+/- 4.6) years, height 182.9 (+/- 5.9) cm, and weight 82.8 (+/- 4.8) kg were studied. A randomized cross-over study design was used with a HF (50.1 g total fat) or low-fat (LF) (5.1 g total fat) test meal 1 week apart. Forearm blood flow was measured over a 2-minute period following a 4-minute occlusion (FBFO) at 2 and 4 hours following ingestion of a test meal. This study found that FBFO was significantly attenuated in Asians (19.3%; p = 0.09) compared to Caucasians after the ingestion of a HF meal. When comparing LF vs. HF meals in Asians, the FBFO were 336.9 ml/100 ml tissue/ minute and 240.8 ml/100 ml tissue/minute, respectively (p = 0.02), whereas in Caucasians, the FBFO were 344.8 ml/100 ml tissue/minute and 287.4 ml/100 ml tissue/minute, respectively. It appears Asians have a more sensitive response to a single HF meal which may be explained, in part, by genotypic variation. These findings suggest that a single HF meal may contribute to the detrimental effects on vascular health in Asian males and raises speculation regarding the cumulative impact of a chronic HF diet in this population. PMID- 20578535 TI - Optimization for high-level expression in Pichia pastoris and purification of truncated and full length recombinant SAG2 of Toxoplasma gondii for diagnostic use. AB - SAG2 is one of the major surface antigens of the intracellular protozoan parasite Toxoplasma gondii. In the present study, truncated recombinant SAG2(S) and full length recombinant SAG2(T) of T. gondii were optimally produced (approximately 15 mg/liter) in Pichia pastoris expression system using BMMY medium at pH 3, 25 degrees C in 0.5-1% methanol and a time-course of 1-2 days. The recombinant proteins were purified using a commercial gel filtration purification system obtaining approximately 33% recovery. The purified SAG2(S) and SAG2(T) showed molecular masses of 45 and 36 kDa by SDS-PAGE, respectively. The recombinant proteins were evaluated by Western blotting with patients' sera and demonstrated 90% sensitivity and 100% specificity for detection of toxoplasmosis. This study provided a means for large-scale expression and purification of SAG2, which should be useful for diagnosis of toxoplasmosis. PMID- 20578536 TI - Vitamin K injection in spontaneous bleeding and coagulopathy in severe malaria: pros and cons. AB - Not all clinicians give vitamin K to severe malaria patients with systemic bleeding. Vitamin K injections may not be useful to stop bleeding in severe malaria patients with predominant hepatocellular jaundice. However, vitamin K may be justified in bleeding patients who have prolonged fasting of more than 3-7 days, underlying malnutrition, or predominant cholestatic jaundice. The decision to give vitamin K to severe malaria patients with systemic bleeding should be based on underlying diseases, type of jaundice, risk for vitamin K deficiency, and allergy to the drug. PMID- 20578537 TI - Three day albendazole therapy in patients with a solitary cysticercus granuloma: a randomized double blind placebo controlled study. AB - A solitary cysticercus granuloma is a benign form of neurocysticercosis. Several reports have suggested albendazole is effective in early resolution of these lesions. A short duration (7 days) albendazole therapy has been found to be effective in treatment. In this study, we evaluated a "three day course" of albendazole in a prospective randomized double- blind trial. Sixty-seven consecutive patients who presented with new-onset seizures and a solitary cysticercus granuloma were randomly allocated to receive either albendazole (15 mg/kg/day for 3 days) or placebo. All patients were treated with antiepileptic drugs. Patients were followed up for 6 months. A repeat CT of the brain was obtained at the end of 6 months of follow-up. The end points were complete resolution of the lesion on CT scan and total seizure control at 6 months follow up. In the albendazole group complete resolution of lesions was noted in 28 of 33 patients (84.8%), while in the control group only 14 of 34 patients (41.2%) had complete resolution of the lesion (p = 0.001). Partial resolution of lesion was seen in 2 patients (6%) in the albendazole group and 4 patients (11.8%) in the control group (p = 0.06). The lesion remained unchanged in 9 cases (26.5%) in the control group only. The lesion became calcified in 7 (20.6%) and 3 (9.1%) patients in the control and albendazole groups, respectively (p = 0.187). Seizure recurrence occurred in 3 patients (9.1%) in the albendazole and 1 patient (2.9%) in the control group (p = 0.239). The three days course of albendazole was effective in resolving lesions, but there was no significant difference in seizure recurrence rates between the two treatment groups. PMID- 20578538 TI - Ectoparasitic fauna of birds, and volant and non-volant small mammals captured at Srinakarin Dam, Kanchanaburi, Thailand. AB - The investigation of ectoparasitic fauna on birds, and volant and nonvolant small mammals at Srinakarin Dam, Kanchanaburi Province, Thailand was carried out under a national biodiversity and disease surveillance program for four consecutive months: January, February, May and June 2009. A total of 122 animals, comprised of 15 species of birds, 9 species of volant small mammals and 8 species of non volant small mammals were examined for ectoparasite infestation. Of these animals, 1 genus of hard ticks (Ixodidae), 2 species of mesostigmatid mites (Laelapidae), 4 genera in three families of astigmatid mites (Proctophyllodidae, Pteronyssidae and Trouessartiidae), 4 species in three families of lice (Philopteridae, Polyplacidae and Trichodectidae) and 2 families of batflies (Nycteribiidae and Streblidae) were collected. This is the first survey conducted to determine ectoparasites infesting birds and small mammals living in the reserved forest of Srinakarin Dam, Thailand. A lower infestation rate of ectoparasites was observed in mammals, ranging from 3.5% to 10.3% than birds, with infestation rates between 7.3% and 34.2%. No major potential health risks to people who lived in this area were found. PMID- 20578539 TI - Breeding patterns of Aedes stegomyia albopictus in periurban areas of Calicut, Kerala, India. AB - Aedes albopictus has been shown to be a vector for diseases which have been on the increase, such as dengue fever and chikungunya infection. We conducted a study of 100 homes from 2006-2009 to determine the breeding sites for Ae. albopictus mosquitoes in Calicut, Kerala, India. We found the larvae of Ae. albopictus mosquitoes most often in coconut shells and plastic waste, followed by tires, flower pots, glass products, egg shells and dumped grinding stones. Ae. albopictus control programs in Calicut, Kerala, India should target these objects as part of a control program. PMID- 20578540 TI - Bionomic status of Anopheles epiroticus Linton & Harbach, a coastal malaria vector, in Rayong Province, Thailand. AB - A longitudinal entomological survey was conducted to provide in-depth information on An. epiroticus and determine whether ecological and entomological factors could influence malaria transmission in Rayong Province, Thailand. The mosquitoes were collected monthly from May 2007 to April 2008 by human landing catch technique from 6:00-12:00 PM for 2 consecutive nights, at 3 collection sites. A total of 3,048 mosquitoes within 5 species were captured: An. epiroticus, Culex quinquefasciatus Say, Cx. sitiens Wiedemann, Aedes aegypti (L.) and Ae. albopictus Skuse. PCR was used for molecular identification of An. sundaicus complex, by determination of COI, ITS2, and D3 genes. The target mosquitoes were An. epiroticus, which was the predominant species, accounting for 43.8% of specimens collected. The biting cycle pattern increased during 6:00-8:00 PM and reached a maximum of 6.6 bites/person/hour by 12:00 PM. The mosquitoes varied in population density throughout the year. The highest biting rate was 37.6 bites/person/ half night in September and the lowest (10.2 bites/person/half night) in January. Nested PCR and real-time PCR techniques were used to detect the malaria parasite in An. epiroticus adult females. Nine of 926 (0.97%) mosquitoes tested were malaria parasite positive: 6 P. falciparum and 3 P. vivax. The infective mosquitoes were found in the dry and early rainy seasons. The overall annual entomological inoculation rate (EIR) in the village was 76.6. The overall parity rate was 74%. A total of 38 cement tanks were used to characterize the nature of the breeding places of An. epiroticus. An. epiroticus larvae coexisted with Aedes and Culex larvae; the maximum larval density was more than 140 larvae per dip in May. Breeding places included fresh, brackish and salt water, typically with full sunlight and mats of green algae on the water surface. The salinity of the water ranged from 0.5 to 119.4 g/l, with a narrow pH range of 8.2-8.7. Dissolved oxygen was highest in November (6.27 mg/l) and lowest in March (3.46 mg/l). The water temperature varied between 24.6 and 32.8 degrees C. PMID- 20578541 TI - The life cycle and effectiveness of insecticides against the bed bugs of Thailand. AB - The purpose of this study was to determine the life cycle and effectiveness of insecticides against bed bugs in Thailand. Bed bugs from dwelling places in Chon Buri and Chiang Mai provinces were determined to be Cimex hemipterus and Cimex lectularius, respectively. Both bed bug species were reared by feeding on rabbit blood at 2-day intervals in laboratory conditions at 28-32 degrees C with 75% relative humidity. The duration from egg to adult stages took 39.9 +/- 7.0 and 36.9 +/- 8.2 days in C. hemipterus and C. lectularius, respectively. The insecticides, propetamphos 20% CS, pirimiphos-methyl 50% EC, bifenthrin 25% WP and alpha-cypermethrin 5% SC, were tested against adult C. lectularius using a Potter spray tower. The concentrations at which 50% of bed bugs were either dead or moribund (ED50) for propetamphos and pirimiphos-methyl were 6.67 and 14.93 mg/m2 for the active ingredients on day 3 and the ED50 for bifenthrin and alpha cypermethrin were 1,767.76 and 353.55 mg/m2, respectively. The results reveal C. lectularius in Thailand has a tendency to develop pyrethroid resistance. PMID- 20578542 TI - Escalated regimen of hepatitis B vaccine in childhood hematological malignancies while on chemotherapy. AB - This prospective study was conducted to find the effective vaccination schedule against hepatitis B virus (HBV) infection for children with hematological malignancies. Sixty patients ages 2-15 years old with hematological malignancies on chemotherapy, negative for hepatitis B surface antigen (HBsAg) and never vaccinated for HBV before, were vaccinated with 40 microg of vaccine at 0, 1 and 2 months. Antibody titers were measured 6 weeks after administration of last dose. Out of the 60 children enrolled, 5 died during the course of treatment and 4 dropped out before completion, leaving 51 for final analysis. More than 70% exhibited protective levels of antibodies (> 10 mIU/ml) against hepatitis B virus. There were no significant effects of age or sex on the antibody response, although antibodies were higher among girls (90.9%) than boys (65%). Patients with non-Hodgkin's lymphoma were found to exhibit a better antibody response than leukemic children (p = 0.024). Children with hematological cancers should be vaccinated with an escalated regimen of the vaccine. PMID- 20578543 TI - Comparison of neuraminidase activity of influenza A virus subtype H5N1 and H1N1 using reverse genetics virus. AB - Neuraminidase (NA) is an envelope surface glycoprotein of influenza A viruses. It cleaves alpha-(2,3) or alpha-(2,6) glycosidic linkage between a terminal sialic acid residue of the host cell receptor and hemagglutinin of the viral envelope, thus releasing viral progeny from the infected cell. In this study, a reassortant virus (H1N1-NA-H5N1) containing the NA gene from A/duck/Phitsanulok/ NIAH6-5 0001/2007 (H5N1) virus and seven remaining genetic segments from A/ Puerto Rico/8/1934 (H1N1) was constructed using reverse genetic technique. NA activity of H1N1-NA-H5N1 virus was lower than that of A/Puerto Rico/8/1934 (H1N1), and NA activity of A/duck/Phitsanulok/NIAH6-5-0001/2007 study (H5N1) was the lowest among them (p < 0.05). To our knowledge, this is the first comparative study of NA activity of H1N1 and H5N1 virus using reverse genetic technique. It also indicates that the NA gene may be expressed at a higher level in the H1N1 infected cell than the H5N1 infected cell. PMID- 20578544 TI - Delayed progression and inefficient transmission of HIV-2. AB - We report a case of HIV-2 infection with delayed progression, taking approximately one and a half decades to develop HIV related symptoms. The spouse was still negative for HIV with a history of having regular unprotected sex with the index case which highlights the inefficient transmissibility of HIV-2. Continued surveillance is needed in screening of HIV-2 infection, especially in cases with a high index of suspicion and risk factors for HIV-2, as these patients develop AIDS related symptoms quite late due to delayed progression. PMID- 20578545 TI - Modeling the incidence of tuberculosis in southern Thailand. AB - The aim of this study was to examine the trend, seasonal and geographic effects on tuberculosis (TB) incidence in the fourteen southern provinces of Thailand from 1999 to 2004. Data were obtained from the National Notifiable Disease Surveillance Report (506), Ministry of Public Health. The joint effects of gender, age, quarterly season and location on the TB incidence rates were modeled using both negative binomial distribution for the number of cases and log-linear distribution for the incidence rate; then these models were compared. The linear regression models provided a good fit, as indicated by residual plots and the R2 (0.64). The model showed that males and females aged less than 25 years had similar risks for TB in the study area. Both sexes had their risk increased with age but to a much greater extent for men than women, with the highest rate noted in males aged 65 years and over. There was no evidence of a trend in the annual incidence of TB during 1999-2004, but the incidence has a significant season variation with peaks in the first quarter over the six year period. There were also differences in the incidence rate of TB both within and between provinces. The high risk areas were in upper western and lower southern parts of the region. The log-linear regression model could be used as a simple method for modeling TB incidence rates. These findings highlight the importance of selectively monitoring geographic location when studying TB incidence patterns. PMID- 20578546 TI - Patterns of drug resistance and RFLP analysis of Mycobacterium tuberculosis strains isolated from recurrent tuberculosis patients in Sri Lanka. AB - The aim of the study was to determine drug sensitivity and DNA fingerprints of Mycobacterium tuberculosis strains from retreatment cases of pulmonary tuberculosis. The study population consisted of 131 culture positive, retreatment tuberculosis patients admitted to the Chest Hospital, Welisara, Sri Lanka who had taken anti-tuberculosis drugs previously. Forty-eight percent of the isolates were susceptible to all 12 drugs tested. Twenty isolates were resistant to first line drugs, 28 to both first and second line drugs and 17 to second line drugs. Forty-six percent were resistant to a single drug, 23% to two and 19% to 3 drugs, respectively. Resistance to p-aminosalicylic acid (15%) was most common followed by ethambutol (14%), isoniazid and pyrazinamide (12%). Multi-drug resistance was present in four isolates. Using RFLP analysis the copy number and IS 6110 element in M. tuberculosis strains varied from one to seven, the majority having 3 to 5 copies. The prevalence of acquired drug resistance to individual drugs was comparatively lower except resistance to ethambutol. The majority of retreatment patients belonged to the defaulter category and this stresses the importance of implementing directly observed treatment short course and susceptibility testing of isolates in retreatment TB patients to prevent the spread of drug resistance. By using the IS 6110 genetic marker it was possible to differentiate most of the M. tuberculosis isolates. However, for an unambiguous confirmation of the identities of strains, additional genetic markers should be employed in strain typing such as spoligotyping. PMID- 20578547 TI - Multiplex PCR for detection of clarithromycin resistance and simultaneous species identification of Mycobacterium avium complex. AB - Multiplex PCR (mPCR) was established for the simultaneous detection of clarithromycin (CLR) resistance and species identification of Mycobacterium avium complex (MAC). mPCR was tested on 218 MAC clinical isolates. CLR-resistance was detected by mPCR in 31 of 35 isolates identified by a microdilution method. Of the remaining 187 susceptible isolates identified by mPCR, 183 isolates had MIC < or = 8 microg/ml (susceptible), 3 with MIC of 16 (intermediate resistant) and 1 with MIC of > or = 32 microg/ml (resistant). Comparing with the PCR-restriction enzyme analysis, mPCR concordantly identified 185 isolates either as being M. avium or M. intracellulare, whereas one isolate was misidentified and 32 isolates could not be identified. Comparing with reference methods, the mPCR showed the sensitivity, specificity, positive predictive and negative predictive value of 89, 100, 100, and 98% for detection of CLR resistance; 92, 98, 99, and 78% for identification of M. avium; and 57, 100, 100, and 89% for identification of M. intracellulare, respectively. PMID- 20578548 TI - Endotracheal tuberculosis with obstruction. AB - Endotracheal involvement of tuberculosis (TB), a type of endobronchial TB, is defined as granulomatous infection of the tracheobronchial tree. We present the case of a 33 year-old female agriculture engineer with endotracheal tuberculosis (ETTB). It was treated successfully with prompt long-course antituberculous medication without complications or need for endotracheal intervention. This unusual case of ETTB, diagnosed promptly by fiberoptic bronchoscopy, and microbiological studies, is presented to emphasize the importance of macroscopic recognition to start anti-TB therapy in cases with significant airway obstruction. This case is important for countries where the various presentations of TB are encountered as well as in countries where TB is not endemic. PMID- 20578549 TI - Coexistence of breast cancer metastases and tuberculosis in axillary lymph nodes- a rare association and review of the literature. AB - The coexistence of metastatic breast cancer and tuberculosis in axillary lymph nodes is very rare. We present the case of a 57-year-old woman with multifocal invasive ductal breast carcinoma in whom the resected axillary nodes were found to harbor both metastatic cancer and tuberculous lymphadenitis. Thorough investigation revealed no evidence of primary tuberculosis elsewhere. A quantiFERON TB-Gold test was positive, indicating latent tuberculosis. The patient was treated with adjuvant chemotherapy antituberculous therapy, radiation and hormonal therapy with aromatase inhibitors. We conclude the possibility of coexistent latent tuberculosis should be kept in mind when granulomatous lesions are identified in axillary lymph nodes with metastatic breast cancer, especially in patients from endemic regions. PMID- 20578550 TI - Detection of outer membrane porin protein, an imipenem influx channel, in Pseudomonas aeruginosa clinical isolates. AB - Decreased permeability to imipenem is the most frequent mechanism of imipenem resistance in Pseudomonas aeruginosa. We have determined the presence of OprD porin protein, an imipenem influx channel, in 70 carbapenem-resistant P. aeruginosa clinical isolates by Western blot analysis using rabbit anti-OprD polyclonal antibody. Ninety-eight percent (54 of 55 isolates) of imipenem-and meropenem-resistant P. aeruginosa clinical isolates were negative for OprD porin production. A small group of isolates resistant to imipenem but susceptible to meropenem (2 isolates) produced OprD protein but at a level 3-5 times lower than the wild type P. aeruginosa ATCC27853 strains. This study indicates that the loss of OprD porin protein was the main mechanism for imipenem resistance in P. aeruginosa clinical isolates. Determination of the status of OprD level in P. aeruginosa may help in the better selection of appropriate carbapenem antibiotics. PMID- 20578551 TI - High prevalence of bla(OXA)-23 in oligoclonal carbapenem-resistant Acinetobacter baumannii from Siriraj Hospital, Mahidol University, Bangkok, Thailand. AB - Acinetobacter baumannii has emerged in health care settings as a pandrug resistant pathogen. Carbapenems are ineffective for treatment of this pathogen. Here we explored the molecular epidemiology and mechanism of carbapenem resistance in clinical isolates of carbapenem-resistant A. baumannii (CRAB). Antibiotic susceptibility by disk diffusion test was performed using imipenem and meropenem disk on 200 different clinical CRAB isolates. All isolates were resistant and gave inhibition zones of both antibiotic disks < or = 13 mm. Polymerase chain reaction (PCR) was carried out on 37 randomly selected isolates to amplify the common carbapenem hydrolyzing beta-lactamase genes (bla(OXA23) like, bla(OXA-24/40)-like, bla(OXA-58), bla(IMP), and bla(VLM)). Clones were resolved by PCR-randomly amplified polymorphic DNA (PCR-RAPD) and plasmid profiling. PCR amplification and DNA sequencing revealed the existence of bla(OXA 23) downstream of the insertion element, ISAba1, in all 37 isolates tested. This segment was present in the carbapenem-resistant genomic resistant island AbaR4. These isolates were resolved into three RAPD types (Type I, 20 isolates; Type II, 16 isolates; and type III, 1 isolate) and 10 plasmid profiles. The CRAB isolates investigated here were oligoclonal and carbapenem resistance was conferred by the presence of bla(OXA-23). The presence of this beta-lactamase gene in many clonal isolates indicated its wide spread. PMID- 20578552 TI - Comparison of Vi serology and nested PCR in diagnosis of chronic typhoid carriers in two different study populations in typhoid endemic area of India. AB - For detection of chronic typhoid carriers, nested PCR targeting flagellin the gene of Salmonella enterica subspecies enterica serotype Typhi was carried out on DNA extracted from hepatobiliary specimens from 424 autopsies which were apparently free from gallbladder pathology on postmortem examination. The second study population was 508 healthy volunteers, who did not suffer from typhoid fever during the preceding year and whose sera were subjected to detection of carriage by estimation of Vi antibody levels using an indirect hemagglutination assay. Males of both study populations had comparable rates of detection by the two methods, 6.3% by PCR and 4.1% by Vi serology. Similarly, females in both study groups had comparable frequency of detection of chronic typhoid carriage using the two methods, ie 13.1% by PCR and 15.1% by Vi serology. S. Typhi specific immunosuppression could be speculated in females of 51-60 years as only 40% were positive by Vi serology against 100% by nested PCR. Vi serology may be recommended for community based detection of chronic typhoid carriers. PMID- 20578553 TI - Is Penicillium citrinum implicated in sago hemolytic disease? AB - Sago hemolytic disease (SHD) is an acute hemolytic syndrome affecting rural Papua New Guineans who depend on the starch of Metroxylon sagu as a staple carbohydrate. It is a suspected mycotoxicosis associated with fungal succession in stored and perhaps poorly fermented sago. Despite a mortality rate of approximately 25%, little is know about the disease. Recent studies have identified Penicillium citrinum as a possible candidate in the etiology of SHD. This is based on the frequency of isolation from sago starch and the hemolytic nature of the organism as demonstrated when cultured on sheep and human blood agar. A highly non-polar lipophilic P. citrinum fraction from C18 solid phase extraction demonstrated high hemolytic activity in a semi-quantitative assay using both mouse and human erythrocytes. When the red cell membrane proteins were subjected to sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation, cleavage of protein band 3 and spectrin was demonstrated. This breach of major structural red cell proteins is consistent with the severe hemolysis found in vivo. Our findings warrant further investigation into the hemolytic activity of P. citrinum and its role as the etiological agent of SHD. PMID- 20578554 TI - A diphtheria outbreak in Assam, India. AB - Between May and July 2009 there was a small outbreak of diphtheria in adults in Assam, India, with 13 confirmed cases, 8 males and 5 females. The mean age of the confirmed patients was 21.8 +/- 10.5 years. Common signs and symptoms of these patients included low grade fever, sore throat and pseudomembranes on the tonsils. The case fatality rate was 30.8%. Neurological complications were observed in one case. None of the patients received antidiphtheric serum (ADS) since none was available. PMID- 20578555 TI - Identification of Ige-binding proteins of raw and cooked extracts of Loligo edulis (white squid). AB - Allergy to different classes of mollusks, including squid, which are members of the class Cephalopods has been reported. Tropomyosin, a major muscle protein, is the only well-recognized allergen in squid. The aim of this study was to characterize IgE-binding proteins of local Loligo edulis (white squid) consumed in Malaysia. Protein profiles and IgE-binding proteins were detected by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE) and immunoblotting using sera from 23 patients with positive skin prick test to raw squid extract. SDS-PAGE of the raw extract exhibited 21 protein bands (10-170 kDa) but those ranging from 19 to 29 kDa and 41 to 94 kDa were not found in the cooked extract. Immunoblotting of raw extract demonstrated 16 IgE-binding bands, ranging from 13 to 170 kDa. A heat-resistant 36 kDa protein, corresponding to squid tropomyosin, was identified as the major allergen of both extracts. In addition, a 50 kDa heat sensitive protein was shown to be a major allergen of the raw extract. Our findings indicate that the allergen extract used for diagnosis of squid allergy should contain both the 36 kDa and 50 kDa proteins. PMID- 20578556 TI - Development of a questionnaire for assessing factors predicting blood donation among university students: a pilot study. AB - University students are a target group for blood donor programs. To develop a blood donation culture among university students, it is important to identify factors used to predict their intent to donate blood. This study attempted to develop a valid and reliable measurement tool to be employed in assessing variables in a blood donation behavior model based on the Theory of Planned Behavior (TPB), a commonly used theoretical foundation for social psychology studies. We employed an elicitation study, in which we determined the commonly held behavioral and normative beliefs about blood donation. We used the results of the elicitation study and a standard format for creating questionnaire items for all constructs of the TPB model to prepare the first draft of the measurement tool. After piloting the questionnaire, we prepared the final draft of the questionnaire to be used in our main study. Examination of internal consistency using Chronbach's alpha coefficient and item-total statistics indicated the constructs "Intention" and "Self efficacy" had the highest reliability. Removing one item from each of the constructs, "Attitude," "Subjective norm," "Self efficacy," or "Behavioral beliefs", can considerably increase the reliability of the measurement tool, however, such action is controversial, especially for the variables "attitude" and "subjective norm." We consider all the items of our first draft questionnaire in our main study to make it a reliable measurement tool. PMID- 20578557 TI - Impact on access to medicines from TRIPS-Plus: a case study of Thai-US FTA. AB - This study assessed the impact of the Thai-US Free Trade Agreement (FTA) on access to medicines in Thailand. We first interpreted the text of the sixth round of Thai-US negotiations in 2006 on intellectual property rights (IPR). The impact was estimated using a macroeconomic model of the impact of changes in IPR. The estimated impact is based on a comparison between the current IPR situation and the proposed changes to IPR. The FTA text involves the period of patent extension from the Trade-Related Aspects of Intellectual Property Rights Agreement (TRIPS Agreement). The provisions involve the period of patent extension, which have to do with compensation for delays in patent registration and/or drug registration, data exclusivity that would result in a delay in generic drug entry, and the enforcing role of the Thai Food and Drug Administration of patent linkages. As a worst case scenario for this single provision, a 10 year patent extension would be given to compensate for delays in patent registration and/or drug registration. The impact on access to medicine, in the year 2027, would be: 1) A 32% increase in the medicine price index, 2) spending on medicines would increase to approximately USD 11,191 million, (USD1 = THB 33.9 on September 2, 2009), and 3) the domestic industry could loss USD 3.3 million. These results suggest there would be a severe restriction on the access to medicines under the TRIPS-Plus proposal. IPR protection of pharmaceuticals per the TRIPS-Plus proposal should be excluded from FTA negotiations. PMID- 20578558 TI - Microbial counts and particulate matter levels in roadside air samples under skytrain stations, Bangkok, Thailand. AB - In conditions with heavy traffic and crowds of people on roadside areas under skytrain stations in Bangkok, the natural air ventilation may be insufficient and air quality may be poor. A study of 350 air samples collected from the roadside, under skytrain stations in Bangkok, was carried out to assess microbial counts (210 air samples) and particulate matter (PM10) levels (140 samples). The results reveal the mean +/- standard deviation bacterial counts and fungal counts were 406.8 +/- 302.7 cfu/m3 and 128.9 +/- 89.7 cfu/m3, respectively. The PM10 level was 186.1 +/- 188.1 microg/m3. When compared to recommended levels, 4.8% of air samples (10/210 samples) had bacterial counts more than recommended levels (> 1,000 cfu/ m3) and 27.1% (38/140 samples) had PM10 levels more than recommended levels (> 120 microg/m3). These may affect human health, especially of street venders who spend most of their working time in these areas. PMID- 20578559 TI - Knowledge and views regarding condom use among female garment factory workers in Cambodia. AB - Cambodia is experiencing a generalized HIV epidemic; there is evidence some populations within Cambodia are particularly vulnerable to infection. A mixed methods study was conducted in 2006 on the vulnerability to contract HIV of rural to-urban migrant Cambodian garment factory workers. This paper reports the views of these female migrant workers regarding the use of condoms in their sexual relationships. Semi-structured interviews were conducted among 20 workers about their knowledge and experiences regarding condom use. Both married and single women were knowledgeable about HIV transmission, but there was a spectrum of perspectives about condom use with their current or future partners. Some women insisted partners use condoms, while others did not expect partner compliance, and a third group avoided discussing condom use with their partners. HIV prevention programs should include male partners. For many of these migrant women, interventions focussing on education about HIV transmission and condom negotiation skills are insufficient since implementation requires male cooperation. PMID- 20578560 TI - Awareness and practice of post abortion care services among health care professionals in southeastern Nigeria. AB - This study investigates knowledge and practices of post abortion care (PAC) services among health care professionals in the Anambra State of southeastern Nigeria. This was a prospective, cross-sectional, questionnaire based study conducted between 1 June and 30 September, 2006. The study involved a multi staged sampling of all registered health facilities in Anambra State, with the selection of 60 health facilities from which 450 participants were recruited. A pre-tested, structured questionnaire was employed to obtain information from the studied respondents. Obtained data were analyzed using Epi-Info version 2001. A total of 437 questionnaires out of 450 administered were accurately completed, giving a response rate of 97.1%. The respondents were comprised of general practitioners (214, 49.0%), nurses (161, 36.8%), specialist doctors (56, 12.8%), and resident doctors (5, 1.1%). The mean age of the respondents was 38.2 +/- 10.5 years. Most participants (203, 52.6%) were males; the majority (282, 64.5%) were working in the rural areas of the State, including mission hospitals (165, 37.8%) and general hospitals (145, 33.3%). Three hundred thirty respondents (75.5%) were aware of PAC services. Twenty-seven (6.2%) and 28 (6.4%) of respondents were aware of community partnership and family planning services, respectively, as elements of PAC. Although the majority of respondents (302, 69.1%) treated abortion complications, only 155 (35.5%) used a manual vacuum aspirator. Three hundred thirty-eight (88.8%) offered counseling services, and 248 (56.8%) provided referrals to other reproductive health services. PMID- 20578561 TI - Antenatal care among ethnic populations in Louang Namtha Province, Lao PDR. AB - One in 33 women in Lao PDR dies due to pregnancy-related causes, which is the highest in Southeast Asia. This study assessed ANC utilization rates and the determinants for these rates; it also explored rural maternal decision-making regarding the place of delivery and immunizations for their children under age five years. A cross-sectional study was carried out in Viengphukha District, Louang Namtha Province, Lao PDR in January 2008. Of 1,005 household representatives, 620 who had children age under five years were interviewed using a semi-structured questionnaire. Nearly one-quarter of mothers (23.4%) had at least one ANC visit during their most recent pregnancy, of which 4.5% had > or = 4 ANC visits. ANC visit rates among lowland and midland mothers were 3.6 and 7.6 times higher than highland mothers, respectively (p < 0.005 and p < 0.001). Mothers with no ANC were more likely to deliver at home (adjusted OR = 18.0; p < 0.0001). Home deliveries were more common among highland than lowland mothers (adjusted OR = 10.5; p < 0.05). Children born to mothers who had no ANC visit were more likely to not complete routine immunization than those who were born to mothers who had ANC visits (adjusted OR = 1.9; p < 0.01). Low ANC utilization rates in Lao PDR were observed among ethnic minority mothers who were less educated. ANC visits enhanced hospital deliveries and child immunizations. The promotion of ANC among women in remote rural communities is needed. PMID- 20578562 TI - Early childhood caries and related factors in Vientiane, Lao PDR. AB - The objectives of this study were to determine the prevalence of early childhood caries and the oral health status in children aged 36-47 months in Vientiane, the capital city of Lao PDR. This study also aimed to assess the feeding practices, snack consumption, oral hygiene practices, and dental visits of children at this age. A total of 400 children were selected for oral examination and their caretakers were interviewed. The results showed the prevalence of dental caries was 82% with mean decayed, missing and filled teeth (dmft) +/- SD 5.5 +/- 4.3 teeth. No missing teeth were found (mt = 0), and the mean filled teeth (ft) was only 0.02. The teeth most affected by dental caries were the upper right and left central incisors, followed by the upper right and left lateral incisors, lower molars, upper molars, upper canines, lower canines and lower central incisors. The least affected were the lower right and left lateral incisors. Factors that affected dmft were tooth brushing frequency, brushing with parental assistance or supervision, time brushing started, feeding pattern, and the type of milk, candy and sweet beverages consumption. It can be concluded that children in the studied area had a high prevalence of caries and a high level of severity. Thus, oral health care programs should be promoted in Vientiane. PMID- 20578563 TI - Association between an unhealthy lifestyle and other factors with hypertension among hill tribe populations of Mae Fah Luang District, Chiang Rai Province, Thailand. AB - An unhealthy lifestyle may lead to hypertension which can cause strokes and cardiovascular disease. The aim of this study was to identify the specific unhealthy lifestyle practices which could cause hypertension among hill tribe populations in Mae Fah Luang District of Chiang Rai Province, Thailand. In 2006, 196 patients with hypertension were selected from 2 district hospitals and 13 health centers as cases, and 196 normotensive subjects from a local neighborhood were chosen as controls. Trained health personnel collected data by interviewing subjects from both groups regarding unhealthy lifestyles and other factors. All participants had a physical examination at the time of interview. The results from multiple logistic regression analysis show the factors associated with hypertension among the hill tribe people studied were smoking (OR 2.48; 95% CI 1.43-4.30, p = 0.001), no or irregular exercise (OR 1.84; 95% CI 1.16-2.99, p = 0.005), being overweight (OR 2.96; 95% CI 1.69-5.18, p < 0.002), having obesity (OR 2.65, 95% CI 1.04-6.73, p < 0.018) and having a high frequency intake of fatty foods (OR 1.98, 95% CI 1.23-3.18, p < 0.013). The findings suggest the need for significant lifestyle changes in regards to smoking, eating habits and leisure time exercise programs. The adoption of such lifestyle changes would result in a reduced chance of being hypertensive, which could later reduce cardiovascular morbidity and mortality. PMID- 20578564 TI - Factors associated with alcohol consumption among male high school students in central Thailand. AB - A cross-sectional study was conducted to explore factors associated with alcohol consumption among male high school students in central Thailand. Five thousand one hundred eighty-four male students from central Thailand were classified into 2 groups according to alcohol consumption during the past year (yes = 916, no = 4,268). Data were collected by an anonymous self-reporting questionnaire which consisted of 2 parts: socio-demographic factors and alcohol drinking behavior during the previous year from December 2007 to February 2008. Descriptive statistics, a chi-square test and multiple logistic regression were used to analyze the data. Seventeen point seven percent of male high school students in this study reported consuming alcohol. Most of the students (73.4%) were 15 years old or younger. Univariate analysis revealed socio-demographic factors, such as age, educational level, residence, cohabitants, grade point average (GPA), having a job earning money and having family members with alcohol/drug problems were significantly associated with alcohol consumption (p < 0.05). Multiple logistic regression analysis, after adjusting for age, revealed five factors were associated with alcohol consumption: the educational level (OR MS3 = 2.69, 95% CI 2.07-3.49; OR MS5 = 5.50, 95% CI 4.25-7.13), cohabitants (OR Friends = 3.09, 95% CI 1.38-6.93), having a job earning money (OR = 1.37, 95% CI 1.13-1.66), having family members with alcohol/drug problems (OR = 1.33, 95% CI 1.11-1.60), and GPA (OR < 2 = 1.31, 95% CI 1.01-1.71; OR > 3 = 0.62, 95% CI 0.51-0.75). Approximately 38% drank more than 2 times a month, 35% drank more than 4 drinks each time, 60% experienced binge drinking, and 43% experienced drunkenness. These results suggest alcohol abuse preventive measures among male high school students should take into account education level, cohabitants, having a job earning money, family members with alcohol/drug problems and GPA. Education regarding the disadvantages of alcohol to risk groups could reduce the proportion of new and current drinkers. PMID- 20578565 TI - A pilot use of team-based learning in graduate public health education. AB - This pilot study was undertaken to determine the impact of team-based learning (TBL) on graduate students of public health in a Thai context. The pilot project adopted Michaelsen's approach with the aim of improving learning among Thai graduate students enrolled in public health ethics. This TBL approach attempted to motivate students to do pre-class reading and be active "in-class" learners. Pre-class preparation allowed teachers to address and concentrate on learning gaps, while team work promoted peer interaction and active learning. TBL was found to be useful in fostering student preparedness and to transform "passive" into "active" learning, which especially benefited students "academically at risk" through peer teaching opportunities. With TBL, students valued the relevance of the course content and learning materials. They had positive opinions regarding the effect of TBL on individual and group learning. TBL was perceived to be instrumental in translating conceptual into applicable knowledge, and stimulated individual efforts as well as accountability. This study should be useful to those considering using TBL for public health education. PMID- 20578566 TI - Health savings accounts and health reimbursement arrangements: assets, account balances, and rollovers, 2006-2009. AB - ASSET LEVELS GROWING: In 2009, there was $7.1 billion in consumer-driven health plans (CDHPs), which include health savings accounts (or HSAs) and health reimbursement arrangements (or HRAs), spread across 5 million accounts. This is up from 2006, when there were 1.2 million accounts with $835.4 million in assets, and 2008, when 4.2 million accounts held $5.7 billion in assets. AVERAGE ACCOUNT BALANCE LEVELING OFF: Increases in average account balances appear to have leveled off. In 2006, account balances averaged $696. They increased to $1320 in 2007, a 90 percent increase. Account balances averaged $1356 in 2008 and $1419 in 2009, 3 percent and 5 percent increases, respectively. TYPICAL ENROLLEE: The typical CDHP enrollee was more likely than traditional plan enrollees to be young, unmarried, higher-income, educated, and exhibit healthy behavior. No differences were found between CDHPs enrollees and traditional plan enrollees with respect to gender, race, and presence of children. MORE ROLLOVERS: Overall, the number of people with a rollover, as well as the total level of assets being rolled over, have been increasing. The average rollover increased from $592 in 2006 to $1295 in 2009. DIFFERENCES IN ACCOUNT BALANCES: Men tend to have higher account balances than women, account balances increase with household income, education has a significant impact on account balances independent of income and other variables, and no statistically significant differences in account balances were found by smoking, obesity, or the presence of chronic health conditions. Individuals who developed a budget to manage their health care expenses had a higher account balance ($1726) than those who did not ($1428), but otherwise, no statistically significant differences in average account balances were found between individuals who exhibited various aspects of cost-conscious decision making behaviors and those who did not. DIFFERENCES IN ROLLOVER AMOUNTS: Men rolled over more money than women, whites have higher rollover amounts than minorities, and the youngest adults and the oldest adults had the largest rollover amounts in 2009. Rollover amounts increase with household income and education, and individuals with single coverage rolled over a slightly higher average amount than those with family coverage. There was no statistically significant difference in rollover amounts by health status, although individuals who smokes ad higher rollover amounts than those who do not and obese individuals had lower average rollover amounts than nonobese individuals. Individuals who talked to their doctor about treatment options and costs, those who used an online cost-tracking tool provided by the health plan, and those who asked their doctor to recommend a less costly prescription drug had higher rollover amounts than those who did not take such actions. PMID- 20578567 TI - [Notes on the Spanish Foundation of Pediatric Surgery]. PMID- 20578568 TI - [Long term follow-up of bile duct stenosis treated with interventional radiology in pediatric liver transplantation]. AB - The reported incidence of biliary strictures following pediatric liver transplantation has ranged between 5-34%, with a higher incidence in segmental grafts. Currently, percutaneous transhepatic balloon dilatation of biliary strictures is considered as the first line treatment owing to its minimal invasiveness. Between 1995-2006, 20 children who underwent liver transplantation developed biliary complications treated with interventional radiology. 16/20 developed biliary stricture, of whom 10 were treated with percutaneous transhepatic balloon dilatation. The mean age at the procedure was 6.6 years (range 8 m--14 years). The allograft types included whole (n=4), split (n=3), and reduced (n=3) livers. The procedure was performed at a mean time post transplantation of 2.6 years. All patients are alive with a mean follow-up post procedure of 24 months (range: 4 months-11 years). Currently, only 4 have a normal appearing biliary tree by imaging techniques and 6 developed stricture recurrence; of whom 3 developed biliary cirrhosis (2 splits, 1 reduced), one patient underwent successful rescue surgery, one was treated again percutaneously, and the remaining was lost to followup. In conclusion, treatment of percutaneous transhepatic balloon dilatation of biliary strictures is effective avoiding surgical correction. However, stricture recurrence in the medium- long term follow-up is frequent, particularly in segmental grafts. [corrected] PMID- 20578569 TI - [Congenital fibroepithelial polyps of the urethra]. AB - Urethral polyps are a rare pathology that is usually diagnosed in childhood hematuria and obstructive urinary symptoms are the most common findings and transurethral resection is the best choice of the treatment. We report three cases, a 6-years-old boy and 9-years-old boy diagnosed and treated of posterior urethral polyp after showing hematuria and obstructive urinary symptoms, and a 2 years-old girl that showed to prolapse of urethral polyp. PMID- 20578570 TI - [Long-term results in ulcerative colitis treated with proctocolectomy and ileoanostomy in children]. AB - AIM: The treatment of Ulcerative Colitis (UC) unresponsive to current medical treatment involves total proctocolectomy and ileanostomy. The aim of this study was to assess the long term results in such patients. MATERIAL AND METHODS: We reviewed children treated from 1992 to 2008. The operations, complications and functional outcome were recorded. For those with preserved rectal defecation, continence (Holschneider score) and quality of life (standardized phone questionnaire) were assessed in the long term. RESULTS: 104 patients had Ulcerative Colitis (UC) and 3 undetermined colitis (excluded from the study). 26/104 UC patients (26%) aged 10.7 +/- 4.1 years required 82 operations. Eight had emergency colectomy for toxic megacolon (3, one death) or severe hemorrhage (5). 25 had restorative proctocolectomy and ileoanostomy (RPCIA) without (16) or with (9) J-pouch under protective ileostomy. Complications were frequent (40%). Permanent ileostomy was required in 5 children (20%). Twelve months postoperatively, RPCIA patients had 6.3 +/- 3 stools/day, all were continent during daytime and 25% have nocturnal leaks. Mean Holschneider score (0-12) was 8.8 +/- 2. Quality of life was good in all with normal school (all) or university attendance (7), 4 work and 60% of those older than 18 have sexual partners. CONCLUSIONS: The nature of UC involves risky and frustrating surgery. However, it may provide a reasonably good quality of life for UC patients after the first year. Pediatric surgeons should be able to provide adequate preoperative counseling to patients and families. PMID- 20578571 TI - [Laparoscopic resection of the prostatic utricle in children]. AB - INTRODUCTION: The prostatic utricle is an embryological remnant from Mullerian duct tissue. Most prostatic utricles are asympomatic, but they may manifest as a urinary tract infection or an incontinence. MATERIAL AND METHOD: Surgery consists in a cysto-urethroscopy and cannulation of the prostatic utricle with a ureteral catheter (Fogarty ner 4) and the cystoscopy left in situ to facilitate identification and mobilization. A 10 mm port through a umbilical incision and two more 5 mm working ports were inserted. After mobilization, the ureteral defect was closed by an absorbable suture and ultrasonic coagulation. RESULTS: Five boys with symptomatic prostatic utricles underwent surgery at a mean (range) age of 7 (2-11) years. The laparoscopic excision was successful in all but one due to a bleeding. The mean (range) operative duration was 165 (120-240) min. CONCLUSION: Laparoscopic excision under cystoscopic guidance offers a good surgical view and allowing easy dissection. PMID- 20578572 TI - [Quality of life in children operated on for anal atresia]. AB - INTRODUCTION: Most children with anorectal malformations have some type of intestinal dysfunction. A correct follow up in this aspect after surgery affects their quality of life. MATERIAL AND METHODS: We gathered a sample of 20 children that were lost in their follow up after posterior sagittal anorectoplasty (PSARP). We got contact with them and they were interviewed and examined in our department. RESULTS: We collected 12 girls and 8 boys. Age range was between 3 and 14 years. 70% had good prognosis for continence (low fistula) and 30% poor prognosis (high fistula). 35% suffered from postoperative complications being the most frequent prolapse especially in high atresias. 85% had good rectal sensitivity, 15% had poor sensitivity that was directly related to incontinence. Anal tone was decreased in our exploration in 35% of patients which was not directly related to their continence. 65% suffered constipation with or without fecaloma. 5% of cases had intestinal hipermotility. The total incidence of fecal loose was 40%. More than a half (62,5%) kept on loosing stool despite treating their constipation or hipermotility, so we consider them true incontinents (no voluntary bowel movements). 67% of children with high fistula were true incontinents, just 7% of those with low fistula. Subjective quality of life in patients with soling was 6.4. In clean patients it was 9.3. Objective quality of life (Score/13) in dirty patients was 6.6. In Clean patients: 11.9. After our bowel management protocol we got 100% of patients clean during school time, thereby improving their quality of life. CONCLUSIONS: Incontinence determines the long-term quality of life in our patients in addition to the psycho-social consequences. They are clearly more frequent in patients with high fistula. Much assume incontinence as an unavoidable part of their disease so do not always demand treatment if they are not followed by a surgeon. PMID- 20578573 TI - [The PEG: why wait?]. AB - The swallowing disorder is an impediment to feed the patient. The percutaneous endoscopic gastrostomy (PEG) offers importants advantages over nasogastric tube feeding in patients who need long-term enteral nutrition with difficulty to swallow and to failure to thrive. METHODS: We have achieved 40 PEG in our department over the past 10 years. We registered date of the age, weight, indications, types of PEG, the time to first change, evolution of weight and percentiles and the complications. RESULTS: The average age of our patients was 5 years, 30% under 1 year. We used mostly tubes between 9 and 15 Fr and increasing the size according to nutritional needs. The average weight at the time of PEG placement was 13 kg. The main indications were the impossibility to swallow and failure to thrive and the principal diagnosis was the encephalopathy in 45% of cases. The surgical technique was successful in 100%. Of the complications, only two patients required surgery, a gastrocolic fistula and a laparotomy about broken tube of gastrostomy that has been caught in the cecum. In our series we reported 11 cases of mortality from causes unrelated to the gastrotmy. CONCLUSIONS: The PEG is a good alternative to nasogastric tube in patients with swallowing disorders or failure to thrive in chronic diseases, even in children under one year. The early placement of the PEG support the growth development in these patients with chronic disease who require enteral nutrition for long periods. Probably, the time of placement should be more precocious in chronic patients as well tolerated and may have a long life with a good care. PMID- 20578574 TI - [Differential diagnosis of the interlabial masses in girls under 5-years-old]. AB - The masses that we can be found at interlabial in a girl are a extensive spectrum of heterogenous lesions and often there is a confusion in diagnosis, management and prognosis. METHODS: We present 5 cases of interlabial masses, prolapsed urethra, two paraurethral Skene cysts, botryoid sarcoma and fibroepithelial polyp, and its clinical of debut. RESULTS: A prolapsed urethra is presented in a 4-year-old black girl with vaginal bleeding from edamatous periurethral mass. The paraurethral cyst is a yellowish cystic mass displacing the urethral meatus in two newborn girls. The fibroepithelial polyp is presented in a newborn girl as polipoid and wartlike tumor and not bleeding injury in the introitus. The botryoid sarcoma appears in a 1-year-old girl with ulcerated polypoid mass of 2 cm from vagina. All cases were treated with surgery except the paraurethral cyst that drained spontaneously and the rhabdomyosarcoma was also treated with chemotherapy. CONCLUSIONS: There must be a good clinical examinations about interlabial masses distinguishing genital or urological origin. The surgery is indicated mainly to reject malignancy because the presentation of sarcoma and polyp could be similar. The prognosis of rhabdomyosarcoma vaginal is good with surgery and chemotherapy. The prolapsed urethra is more common in prepubertal black girls and it is important to exclude sexual abuse. The management of paraurethral cyst is controversial but some authors are advised first observation because they may regress. PMID- 20578575 TI - [Should horseshoe kidneys with associated urological abnormalities be controlled?]. AB - INTRODUCTION: Horseshoe kidney (HK) is the most common renal fusion anomaly. Urological anomalies (UA) occurs in 52% of HK. The objective of this paper is to know if it's necessary to follow up for a long time the asymptomatic cases of HK with UA. MATERIAL AND METHODS: We reviewed retrospectively 39 cases of children in whom HK was diagnosed in our hospital during 1990 to 2007. The following features have been taken into account: sex, age at diagnosis, associated anomalies, treatment, postoperative complications, results and time of follow-up. RESULTS: The mean age at diagnosis was 3 years. 18 patients (46.1%) had associated urological anomalies: 9 hydronephrosis, vesicoureteral reflux 6 and 3 kidney duplication. 10 cases of them (55%) were surgically treated: 6 pyeloplasty, 2 endoscopic reflux, one upper pole heminephrectomy and one ureteroneocystostomy. 3 hydronephrosis and 3 vesicoureteral reflux were managed conservatively. The ureteropelvic junction obstruction (UJO) was caused by a crossing lower-pole vessel in four cases (67%) and two by a high ureteral insertion. Three of this cases of obstruction (50%) were adquired over the time (along 5-7 years from diagnosis of hydronephrosis). There were no complications and the mean time of follow up has been 3.6 years (range: 2-6 years). CONCLUSIONS: We think that all HK associated with UA should be controlled, as above 50% are subsidiaries of surgical correction. The hydronephrosis can be obstructive over the time and it could be necessary to check them for a long time. PMID- 20578576 TI - [Familial adenomatous polyposis: a follow-up of the extracolonic manifestations]. AB - INTRODUCTION: Total colectomy is the only effective treatment for prophylaxis against colon cancer in patients with familial adenomatous polyposis (FAP). We present our experience with 4 children colectomized for FAP, with a particular focus on the long-term surveillance to detect extracolonic manifestations. PATIENTS AND METHODS: We review the clinical histories of 4 patients from 10 to 16-years-old, with family histories of FAP. Performed for each patient were: genetic testing, colonoscopy, double contrast enema, gastro-oesophageal duodenoscopy, thyroid and abdominal ultrasound, fundus oculi, and tumour markers (CEA, CA 19.9). They underwent total colectomy with ileoanal anastomosis and anorectal mucosectomy with an ileal J-pouch. During follow-up, they were monitored regularly with imaging techniques (including a video capsule in one patient) and endoscopy. Also evaluated were faecal continence, food intake, and height-weight development. RESULTS: All had multiple polyps in the colon, and mutation of the APC gene. Hypertrophy of the retinal pigment epithelium was observed in three. Immediately postoperative, there were abundant diarrhoeic stools, two presented an episode of "pouchitis", and one moderate undernourishment. One patient had an intraperitoneal haemorrhage that was resolved by blood transfusion. All 4 have normal faecal continence. During the first months postoperative, two patients showed considerable weight loss. In the follow-up (> 3 years), moderate undernourishment was observed in one patient. Duodenal polyps were found in two patients--in one by duodenoscopy, and in the other with the video capsule. CONCLUSIONS: After colectomy, FAP patients may develop extracolonic clinical manifestations, some of which may be malignant such as thyroid and periampullary cancer. Careful surveillance of these patients is therefore very important, with annual checks using gastroduodenoscopy and thyroid and abdominal ultrasound. PMID- 20578577 TI - [Anorectal manometry in the neonatal diagnosis of Hirschsprung's disease]. AB - OBJECTIVE: To determine the usefulness of anorectal manometry (AM) in neonatal screening for Hirschsprung's disease (HD). MATERIAL AND METHODS: We review the anomanometric studies of 98 newborn (63 males and 35 females) with clinical suspicion of HD, noting the indications of AM, gestational age, weight, age in days at the test, and whether or not other diagnostic methods were performed. Studied at rest were the pressures (mmHg) in the rectal ampulla (RA), proximal anal canal (PAC), and distal anal canal (DAC), and, in the stimulation phase, the presence or absence of a recto-anal inhibitory reflex (RAIR). In patients with no RAIR, the study was repeated weekly until the end of the first month, and if there was still no RAIR a suction rectal biopsy (SRB) was performed. In these patients and those with signs of intestinal obstruction, a contrast enema was carried out. RESULTS: The indications of AM are: delayed meconium passage, abdominal distension, and/or vomiting in 61.5% of the patients, intestinal obstruction in 16%, constipation in 15.1%, and other causes in 7.4%. The mean gestational age was 35.59 +/- 4.59 weeks, and the weight 2518 +/- 912.91 g. The mean age at the first test was 15.08 +/- 11.33 days. A RAIR was observed at the first study in 65 patients (healthy 54, meconium plug 2, meconium ileus 2, intestinal neuronal dysplasia 1, false negative 1, and other diagnoses 6), and was absent in 27 (HD 20, small left colon syndrome 4, hypoganglionism 1, and false positives 2). In 6 patients the first study was considered invalid. Histological studies confirmed HD in 21 newborn, in 11 of whom the contrast enema showed a transition zone. There were no differences between healthy and HD newborn in the RA, PAC, or DAC resting pressures. The sensitivity of AM for the diagnosis of HD was 95% and its specificity 90.24%. The sensitivity and specificity of rectal biopsy were 100%. The sensitivity of contrast enema was 52.3%, and its specificity 78.6%. CONCLUSIONS: AM is a simple and safe method with high sensitivity and specificity for the neonatal diagnosis of HD. We consider it indicated prior to SRB in every newborn with clinical suspicion of this disease. PMID- 20578578 TI - [Digestive malformations and their associations to syndrome condition and genetic defects]. AB - INTRODUCTION: The incidence of disease syndromes and genetic defects in patients with malformations is much higher than in the general population. We reviewed our experience in infants with gastrointestinal malformations to know the incidence of genetic defects and syndromic presentation, for purposes of carrying out the most complete assessment and treatment. MATERIAL AND METHODS: We recruited 161 patients with one or more malformations or congenital gastrointestinal pathology. We evaluated: type of malformation (isolated or syndromic), association with polimalformative complex, genetic testing and its results. RESULTS: The main diagnosis, from highest to lowest incidence, is intestinal malrotation (17.18%), Hirschsprung's disease (13.64%), Meckel's diverticulum (13.14%), oesophageal atresia (12.13%), anorectal malformation (11.12%), diaphragmatic hernia (6.57%), duodenal atresia (5.56%), small bowel atresia (4.55%), omphalocele (4.04), and other (12.07%). In 45.3% the malformation is not isolated. 27.4% appear as syndrome, 4.1% as development defect and 2.7% as association. Genetic study was performed in 30.43%, detecting defects in 36.7% of the studies. Down syndrome (n = 8) is the most frequent. DISCUSSION AND CONCLUSIONS: Our experience with these patients is similar to that provided in the literature. We consider that it is important to identify any associated anomalies, especially heart disease, craniofacial anomalies and other gastrointestinal malformations, because they condition the patient's management. Pathologies that are often associated with other defects require more effort for their detection. The knowledge of these patients is essential for correct treatment. PMID- 20578579 TI - [Relationship between the radiological length of the opaque enema and the aganglionic length of the segment in Hirschsprung's disease]. AB - INTRODUCTION: Barium enema was the first method used for the diagnosis of Hirschsprung's disease, with the appearance of anorectal manometry and its combination with rectal suction biopsy, barium enema has lost value as a diagnosis method but it has also gain importance to decide the surgical technique that will be used for the correction of the disease. AIM: To determine the correlation between the length of the affected segment showed by barium enema valued and the length of the removed piece. MATERIALS AND METHODS: We have studied all Hirschsprung disease's cases diagnosed and treated in our center since 1998, 127 patients underwent Soave-Boley's technique and 51 De La Torre's descent technique. Routinely preoperative barium enema was performed in all cases and determine the location of the transition zone and compared with the aganglionic segment's length specified by pathologist. RESULTS: At 90% of cases the transition zone could be seen at barium enema, it's most common location was rectosigmoid. After statistically analysis the length measured at radiology tests and the length of the anatomic piece showed a low correlation (kappa index 0.0159), being highest values at rectosigmoid transition and very low values at long affected segments. CONCLUSIONS: Barium enema in Hirschsprung's disease is valuable to decide the best surgical technique in each singular case but not to determine the exact length of affected segments. In case of a aganglionic long segment suspicion, biopsies may be necessary to determinate preoperative length of affected segments. PMID- 20578580 TI - [Initial study of an experimental model for bladder augmentation]. AB - Since Coffey described in 1910 the Uretero-sigmoidostomy, the first auto continent urinary derivation, many techniques have been developed and used for bladder augmentation, although none of them has been considered fully satisfactory. The availability of a product made of a bovine collagen and glycosaminoglycan base, used for regenerating dermis and oral mucosa induced us to start this study on rabbit bladder in order to verify if muscular fibers might grow in its interior. For that purpose we used 6 New Zealand rabbits, to which we implanted a fragment of artificial dermis inside the detrusor after dissecting it. We present our results after 3 and 6 weeks postoperatively. PMID- 20578581 TI - [Prenatal techniques to prevent central nervous system malformations in the surgically induced model of myelomeningocele]. AB - AIM: To describe central nervous system malformations in the surgically induced model of Myelomeningocele (MMC) and their prevention using different prenatal treatments. METHODS: MMC was surgically created in 33 fetal lambs. Fifteen did not undergo fetal repair (group A). Of the lambs that did undergo repair, 10 were repaired with open two layer surgical closure (group B), 5 with fetoscopic coverage using bioglue (group C) and 3 fetoscopically using a patch (group D). All procedures were recorded and lamb brains and spinal cords were examined grossly and microscopically in coronal sections for structural organization anomalies. Histopathological changes were assessed using HE and S-100 neural marker. RESULTS: Hydrocephalus, Arnold-Chiari type II (AC-II) malformation and some neuronal migration disorders were observed in group A. Brains from group B and D were not hydrocephalic and had neither cell migration disorders nor hindbrain herniation. Group C presents mild degrees of hydrocephalus and AC-II. In group C lumbar lesion was covered by fibrous tissue. CONCLUSIONS: Some of the central nervous system abnormalities observed in human disease are present in the surgically induced model of MMC. In this model avoidance of fluid drainage using open fetal surgery limits malformation severity. PMID- 20578582 TI - [Esophageal atresia in the Goldenhar syndrome]. AB - Among the multiple congenital defects associated to esophagueal atresia, the characteristic ones of the Goldenhar syndrome usually are not included. The high incidence has been reported, about 5% of esophagueal atresia in patients with Goldenhar syndrome. Our experience includes two patients with this association who presented anesthetic problems and surgical complications associated with gastroesophageal reflux and esophageal anastomosis. PMID- 20578583 TI - [Is polycystic ovary syndrome a component of autoimmune disease?]. PMID- 20578584 TI - [The issue of early defibrillation]. PMID- 20578585 TI - [Peroral hormonal contraception and risk of venous thromboembolism]. AB - Oral contraceptives increase the risk of thromboembolism. Recent studies have indicated that the risk of thromboembolic disease in users of combined oral contraceptive pills varies not only with estrogen dose, but also with the type of gestagen in pills with the same estrogen dose. We describe 8 women from our intensive care unit who developed a deep venous thrombosis while on oral contraceptives. The aim of this article is also to discuss other risk factors for the potential risk of venous tromboembolism in users of combined oral contraceptive. PMID- 20578586 TI - [Evaluation of cardiovascular high risk population in specialist ambulatory care: ESA]. AB - BACKGROUND: Arterial hypertension is the most common CV disease in the Czech Republic with estimated prevalence 35% among population aged 25 to 64 years. Although serious public health problem with significant medical and economic consequences the treatment of HT is currently unsatisfactory. Only 18.4% of patients with arterial HT reach goal BP. There are several factors responsible for this fact, among them low compliance of patients, low dosages of antihypertensive drugs used and low usage of the combination of antihypertensive drugs. AIM: To obtain following data from the specialists ambulances (internists and cardiologists) regarding hypertensive patients: frequency of high risk hypertensive patients and proportion of patients with hypertension in whom BP is well controlled (target BP reached). Another goal of the study was to obtain data about pharmacological treatment of hypertensive patients. METHOD: National, multicenter, non-interventional, cross sectional, representative sample, one visit study. RESULTS: Data of 19,821 patients with primary hypertension visited office-based internists and cardiologists was analysed. The average age was 64 +/ 12 years (range 19-99 years), 53% was women. The mean blood pressure of entire population was 138.5 +/- 15.1/81.7 +/- 9.1 mm Hg. There were high proportion of patients with well controlled blood pressure (BP below 140/90 mm Hg)--48% of the patients. Among those with diabetes the proportion of well controlled patients was much lower--only 11% of the patients. Regarding other cardiovascular risk factors the most common was hyperlipidaemia--66% of the patients, following by diabetes and smoking with 29 and 14% of the patients respectively. 8,444 (43%) of the patients suffered from the coronary artery diseases, 2,251 (11%) patients have experienced stroke or TIA and 1,601 (8%) patients had peripheral artery disease. Regarding antihypertensive therapy, only 21% of the population was treated by monotherapy. The most common was the combination of ACE inhibitors plus beta-blockers or triple-combination of ACE inhibitors plus diuretics plus beta-blockers. PMID- 20578587 TI - [The prevalence of anemia and its impact on hospitalization mortality in patients with acute heart failure]. AB - AIM OF STUDY: To evaluate the influence of entry hemoglobin level on the hospitalization mortality of the patients admitted with AHF caused by 4 major etiologies--acute coronary syndrome with ST elevation (STEMI, n = 325) and without ST elevation (nonSTEMI, n = 210), decompensated chronic ischaemic heart disease (IHD, n = 206) and dilated cardiomyopathy (CMP, n = 88). RESULTS: We analyzed 1,253 consecutive 1st-time hospitalizations of AHF patients of whom 1,212 had their entry hemoglobin known. Out of these, 829 subjects were of STEMI (1), nonSTEMI (2), IHD (3) and CMP (4) etiology and were included in further analyses. We devided these patients into subgroups according to hemoglobin levels: I--no anemia, II--minor and III--severe anemia. The hospitalization mortality in subgroups (I-II-III) of each etiology was 16.9-24.5-35.3% (1); 12.4 9.8-35.7% (2); 9.0-9.7-18.2% (3); 1.5-21.4-33.3% (4); all etiologies together 12.4-15.0-28.8%, total rate 14.1%. Univariate analysis (chi2) showed significant differencies in hospitalization mortality depending on etiology and hemoglobin level but not type of failure (de novo/decompensation). Other parametres (comorbidities, laboratory and hemodynamic values, medication at entry) had a very variable impact on mortality throughout etiologies and hemoglobin subgroups. CONCLUSION: The presence of anemia increases hospitalization mortality of patients with acute heart failure. The relation between hemoglobin level and mortality seems to be linear, we did not observe "U shape" type of relation. It is necessary to distinguish etiologies of AHF as well as consider effects of laboratory and anamnestic variables when interpreting the results. PMID- 20578588 TI - [The progress of autonomic parameters in patients after myocardial infarction with ST elevation]. AB - The patients after myocardial infarction with ST elevation (STEMI) are endangered by the development inception of autonomic dysfunction, decreased baroreflex sensitivity, decreased heart rate variability, and increased blood pressure variability as a result of increased sympathetic activity and/or decreased parasympathetic activity. Thanks to direct angioplasty and optimal pharmacotherapy of coronary artery disease and heart failure, we didn't found any significant changes of these parameters within a one-year follow-up, and mortality due to cardiac etiology was very low in this group. Autonomic dysfunction and negative left ventricular remodeling is related only to a small group of patients after STEMI, whose risk stratification will be difficult. PMID- 20578589 TI - [Familial hypercalcemia and hypophosphatemia: importance in differential diagnosis of disorders in calcium-phosphate metabolism]. AB - Hypercalcemia and hypophosphatemia are symptoms of two relatively rare hereditary diseases and are extraordinarily important from the standpoint of the differential diagnosis. Mutation in calcium sensing receptor gene (CaSR) clinically manifests as familial hypocalciuric hypercalcemia (FHH) or as the much more serious neonatal hyperparathyreosis. Hypercalciuric hypocalcemia is extremely rare. Prognosis for the most frequent mutations in the CaSR gene FHH is considered benign; nevertheless, if overlooked it can lead to an incorrect diagnosis of primary hyperparathyreosis, which has a fundamentally different prognosis and treatment. Familial hypophosphatemia sometimes occurs as hereditary rickets, which is a consequence of insufficient production of vitamin D-hormone or abnormal function of vitamin D receptors (VDR). The disease manifests as X linked dominant hypophosphatemic rickets or autosomal dominant hypophosphatemic rickets. Autosomal recessive form is very rare. Oncogenic hypophosphatemia should be excluded in differential diagnosis. In this review the issues of pathogenesis, differential diagnosis and treatment of FHH and hypophosphatemic rickets are discussed. PMID- 20578590 TI - [A review of the effects of prolactin hormone and cytokine on the development and pathogenesis of autoimmune diseases]. AB - Prolactin (PRL) is not only a pituitary hormone with important role in the reproduction but it also acts as a cytokine involved in the immune response. Prolactin is produced by many immune system cells that express the prolactin receptor (PRL-R). PRL is then able to affect local microenvironment of the immune system organs and contribute to maturation as well as functioning of the immune system cells. The role of PRL in the immune reactions is stimulating; its presence significantly increases the ability of the immune cells to proliferate and produce cytokines such as TNF-alpha, IFN-gamma, IL-12, IL-1 beta. This effect results from activation of a number of intracellular pathways (Jak2/STAT, Ras/Raf/MAPK etc.) and activation of the genes linked to apoptosis and proliferation (Bcl-XL, Bcl-2, pim, XIAP) or transcription factors (IRF-1). Interestingly, PRL itself is unable to initiate an immune reaction; it is more a factor maintaining balance within immune reactions, contra-regulatory to glucocorticoids, which effect is manifested under critical circumstances of physical or psychological stress. Intensified immunosuppression during stress, combined with a lack of prolactin, has surprisingly been identified during experiments on mice and is also found in human medicine. On the other hand, increased prolactin serum levels were described in several systemic as well as organ-specific autoimmune diseases. PRL levels elevation in these diseases might result from several factors: an increased release of prolactin from the anterior pituitary due to inflammatory cytokines or reduced production of suppressive dopamine, or, alternatively, an increased production of prolactin in immune system cells. In some of these diseases, such as celiac disease and systemic lupus erythematosus (SLE), the PRL level correlates with the disease activity. This supports the hypothesis that PRL oversupply shifts the balance in the immune response towards higher activity of the immune system cells and initiation of the immune reaction. For example, in SLE, prolactin prolongs the life cycle of autoreactive B-lymphocytes and their ability to produce pathogenic autoantibodies. Further research into the effects of PRL and monitoring of patients with hyperprolactinaemia and autoimmune diseases will provide guidance on how to best utilize the possibly so far hidden prolactin potential. It is questionable whether pharmacotherapy could be used to decrease serum PRL levels in the treatment ofautoimmune diseases. However, the currently running studies suggest it might be possible to use PRL level detection as a marker of a disease activity. PMID- 20578591 TI - [Polycystic ovary syndrome and autoimmune diseases]. AB - Polycystic ovary syndrome (PCOS) is characterized by laboratory or clinical signs of hyperandrogenism with chronic anovulation and is currently one of the most frequent endocrinopaties in women of fertile age. Syndrome is associated with a variety of endocrine and metabolic disturbances and according to results of scientific work could be possibly associated with some autoimmune diseases. It seems that the prevalence of autoimmune tyroiditis is important among these patients. Recent studies reveal higher incidence of organ - non specific autoantibodies, but their clinical significance is unknown to date. Further studies are required to determine the role of organ specific and non-specific autoantibodies in patients with PCOS. According to determine an etiology of the syndrome one of the possible outcomes could be investigation of anti-follicular antibody. PMID- 20578592 TI - [The heart of a patient with type 1 diabetes]. AB - The heart of a patient with type 1 diabetes might be affected by ischemic heart disease, cardiovascular autonomic neuropathy as well as diabetic cardiomyopathy. These diseases might occur in isolation, although, more frequently, their effects are combined. Also, these co-morbidities have common risk factors. The aim of this review paper is to summarise the options currently available for the diagnostics, prevention and treatment of the listed heart diseases and, since the most frequent cause of death in the type 1 diabetes patients are cardiovascular diseases, to emphasise the fact that these patients should have cardiology assessment. To ensure clarity of the paper, each disease is discussed in a separate chapter. PMID- 20578593 TI - [Gender differences in non-pharmacological treatment of chronic heart failure]. AB - Prior studies demonstrated sex-related differences in many aspects of chronic heart failure (HF), and in the appropriate use, individual response or complication rates with non-pharmacological treatment, too. There is seasonal variability in morbidity and mortality of HF with significant gender differences, partially due to respiratory diseases, which may be potentionally preventable by vaccination. Quitting smoking is associated with substantial decrease in morbidity and mortality in HF patients which is similar in magnitude to the effect of an appropriate beta-blocker use. Yet little emphasis has been placed on smoking cessation strategies in women with HF and should be adopted as vigorously as proven medical therapy. Complications of catheter ablation for atrial fibrillation were more frequent in females. Gender disparity exists in the use of implantable cardioverter-defibrillators and cardiac resynchronization therapy, although they are beneficial for both women and men. Smaller women have limited access to left ventricular assist device (LVAD) because these devices require a minimum body surface to fit properly. Women were more likely than men to develop severe right ventricular failure after implantation of LVAD. Lower cut-off level of peak oxygen consumption was suggested for women to determine optimal timing for heart transplantation. Disease management programs probably narrows gender differences in quality of care and survival among HF patients. Women with HF have less access to cardiologists, although this consultation is associated with better quality of care, particularly for women. Despite these known sex differences, recommendations for HF are the same for women and men, because prospective sex-specific clinical trials have not been performed. PMID- 20578594 TI - [ILCOR recommendation on signage of automated external defibrillators (AEDs)]. AB - Early defibrillation is a determinant of survival in both out-of-hospital and in hospital cardiac arrests from ventricular fibrillation and pulseless ventricular tachycardia. The review summarizes importance of early defibrillation with automated external defibrillators (AED) and presents the International Liaison Committee on Resuscitation (ILCOR) recommendation for universal AED sign. The aim of the recommendation is to unify the AED signs worldwide and to spread the knowledge of this. The public in general, but healthcare professionals particularly, should be able to recognize AED location and use the device immediately in case of cardiac arrest. PMID- 20578595 TI - Bullying and harassment at workplace: are we aware? PMID- 20578596 TI - Birth weight estimation--a sonographic model for Pakistani population. AB - OBJECTIVE: To develop a sonographic birth weight estimation model for Pakistani population and to validate the published models in the same population. METHODS: Data was collected for pregnant women who presented to Radiology Department of Aga Khan University Hospital Karachi from January 2007 to July 2008 and had undergone ultrasound estimation of foetal weight within 4 days prior to a term delivery (37-42 weeks gestation). The neonate's actual birth weight was used to validate the published foetal weight estimation models and modified sonographic birth weight estimation model was derived for our population by using linear regression. RESULTS: Modified sonographic birth weight estimation model for our population was derived by using foetal parameters. No significant difference (p value > 0.05) of actual and predicted birth weight derived from Our regression model, Campbell and Woo models was noted, however least difference (p = 0.7) was identified between our predicted model (Mean difference 14 +/- 37.7 g). CONCLUSION: Our sonographic modified regression model of foetal weight estimation gave the least difference with actual neonatal birth weight and can be reliably used in our population. Hadlock1, Hadlock2 and Woo2 models are not appropriate in our setting or should be used carefully while predicting foetal weight in our population. PMID- 20578597 TI - An "on the spot" test for targeted screening in index families of thalassaemia. AB - OBJECTIVE: To assess the usefulness of One Tube Osmotic Fragility Test (OTOFT) for "on the spot" screening of rural families with history of thalassaemia. METHODS: It was an "observational cross-sectional" study conducted at Pathology Department of PNS Shifa Hospital, Karachi and included all available members of three families from the rural district (Badin) in Pakistan with history of at least one child with thalassaemia major. One drop of finger prick blood was added to 5 ml of 0.36% saline in a test tube (diameter 2cm). The results were read after 5-10 minutes by visualizing a written material through the contents of the test tube. In addition, samples were also collected for blood counts, Hb electrophoresis and serum ferritin. RESULTS: OTOFT was positive in 135/171 (79%) subjects. In the 135 positives, subsequent investigations showed that 61 (45%) had thalassaemia trait, 52 (39%) had iron deficiency and 22 (16%) had neither of the two and were considered false positive. In the 35 OTOFT negative subjects none had thalassaemia trait while only one had iron deficiency (false negative). CONCLUSIONS: OTOFT is a simple and cost effective test which can be used in the field for screening index families with thalassaemia. While a positive test is sensitive for detection of thalassaemia or iron deficiency an OTOFT negative individual may be excluded from further testing for thalassaemia. PMID- 20578598 TI - Procedure indications and outcome of percutaneous coronary interventions in a tertiary care hospital. AB - OBJECTIVE: To determine clinical indications and one month outcome of Percutaneous Coronary Interventions (PCI) in a tertiary care centre. METHODS: We prospectively conducted a descriptive study on 259 symptomatic coronary artery disease patients, who underwent primary, rescue or elective PCI with stent deployment at the Tabba Heart Institute, from May 2005 to September 2006. The primary objective of the study was to identify--stable angina, unstable angina, Non-ST elevation myocardial infarction (NSTEMI), ST elevation myocardial infarction (STEMI), congestive heart failure (CHF) and cardiogenic shock) and thirty days outcome of PCI in terms of mortality, peri-procedural myocardial infarction, re-infarction and stent thrombosis. This was done according to the standard guidelines of Canadian Cardiovascular Society and New York Heart Association classification. The patients were followed for one month and complications were noted. RESULTS: The mean age of sample was 54.9 +/- 10.6 years. The indications were stable angina (32.4%), unstable angina (13.9%), NSTEMI (18.9%), STEMI (35.1%), CHF (5.4%) and cardiogenic shock (1.5%). The outcome was mortality (2.7%), peri-procedure MI (0.4%), re-infarction (3.08%), cardiogenic shock (1.5%) and stent thrombosis (4.3%). CONCLUSION: Our clinical indications and outcome are comparable with international findings. Stable angina was a major indication and stent thrombosis was the major complication observed, particularly after primary percutaneous intervention for STEMI. PMID- 20578599 TI - Nasoalveolar molding of bilateral cleft of the lip and palate infants with orthopaedic ring plate. AB - OBJECTIVE: To introduce a simple, self-retentive and cost effective presurgical infant orthopaedic plate with anterior ring to retract and align the grossly protruded and deviated pre-maxilla and to perform the nasoalveolar moulding in order to facilitate initial lip repair. METHOD: The study was conducted in the orthodontic department of dental section of CH & ICH Lahore. The nonprobable purposive sample consisted of 35 subjects (27 males, 8 females) with a median age of 7 days (1-13 days). Nonsyndromic patients with bilateral complete cleft lip and palate were included in the study, patients were treated with custom made orthopaedic plate with an acrylic ring around the protruded premaxilla for around 3 months. Anthropometric readings and cast impressions were used to calculate the pre and post treatment differences, the data was tabulated and analysed using SPSS v 12. RESULTS: The results showed highly significant (<.005) difference between the pre and post treatment records of variables except the intercanine distance where the results are significant, i.e., (< 0.05). CONCLUSION: The orthopaedic plate causes significant retraction of the premaxillary segment without applying extra oral forces. It produces columellar elongation and increase in prolabium length facilitating the primary cheiloplasty and rhinoplasty to be precise and without additional scarring PMID- 20578600 TI - Endophthalmitis in paediatric penetrating ocular injuries in Hyderabad. AB - OBJECTIVE: To determine the frequency, risk factors, and visual outcome of post traumatic endophthalmitis in children. METHODS: The study was conducted on patients less than fifteen years age, presenting with penetrating ocular injuries and associated with endophthalmitis. Anterior segment slit lamp examination and if possible posterior segment slit lamp examination with 90 D fundoscopes was performed. After completing necessary investigations, urgent surgical intervention was carried out. RESULTS: There were 43 registered patients with 29 (67.4%) males and 14 (32.6%) females. Twenty three (53.4%) children presented on the day of injury. Remaining 20 (46.6%) reported after first 24 hours. Twenty seven (62.7%) children presented with corneal wound, 11 (25.6%) had scleral entrance, and 5 (11.7%) patients had corneo scleral extension. Nineteen (44.1%) patients developed clinical evidence of endophthalmitis. Fifteen subjects with endophthalmitis completed six weeks follow up. Two (13.3%) subjects achieved final visual acuity (FVA) of 3/60. Four (26.7%) had only hand movements, 5 (33.4%) subjects were restricted to perception of light, and 2 (13.3%) patients developed phthisis bulbi. CONCLUSION: Delayed arrival of patients in eye hospital with open globe injury may result in endophthalmitis PMID- 20578601 TI - Patient satisfaction of depot medroxyprogesterone acetate (dmpa-sc) injection as contraceptive. AB - OBJECTIVE: To determine Patient Satisfaction of DMPA-SC (104 mg/0.65 mL) injected subcutaneously once every 3 months. METHODS: It was a Descriptive case series with the centre in Rawalpindi (Holy Family Hospital, Gynecology and Obstetrics Unit), Pakistan. Twenty five patients were selected by purposive sampling and followed up in Rawalpindi center (Holy Family Hospital, Gynaecology and Obstetric Unit) for one year as a part of the Asian Trial These patients had successfully completed their contraception using DMPA-sc at 3 months interval. Hospital Ethical Committee Permission was obtained prior to commencement of study. Informed written consent was taken from the patients. Body weight was measured at baseline and every 3 months thereafter. Bleeding analysis was also done at 3 months interval using a 5 point scale based on patient's own records. Participant satisfaction with treatment results was evaluated using a patient satisfaction questionnaire (PSQ). It collected data regarding the respondent's experience with the study, the aspects of treatment that were liked and disliked and the likelihood of selecting that method for future contraceptive purposes. RESULTS: Out of twenty five, 15 (60%) patients had a high inclination Six (24%) patients and 9 (36%) very highly likely to use this contraceptive method in future. Eleven (44%) women replied that the probability of recommending this contraceptive method to their friends was very highly likely. CONCLUSIONS: DMPA-SC has a very high percentage score of Patient Satisfaction for the contraceptive method as well as its likelihood of selecting it in future (JPMA 60:536; 2010). PMID- 20578602 TI - Prevalence of malignant disorders in 50 cases of postmenopausal bleeding. AB - OBJECTIVE: To find the prevalence of malignant pathology in women with postmenopausal bleeding (PMB). METHODS: An observational cross section study was conducted in the Department of Obstetrics and Gynaecology at Peoples Medical College and Hospital Nawabshah from 1st January 2006 to 31st December 2006. All patients with a typical history of post-menopausal bleeding were evaluated under anaesthesia and diagnostic dilatation and curettage was done for histopathological assessment of endometrial lining. Cervical biopsy was taken in selected patients. RESULTS: Total 50 patients were included. Benign lesion was found in 24 (48%) cases, followed by malignant pathology in 15 (30%), premalignant lesion was responsible for PMB in 7 (14%) cases, while pathology remained undetermined in 4 (8%) patients. CONCLUSION: Malignancy has an important role in the etiology of PMB which needs a careful evaluation. This study showed a high prevalence of malignant disorders (30%) with carcinoma of cervix and endometrium having an equal contribution. Multiparity was the most significant factor for carcinoma of endometrium. PMID- 20578603 TI - Stunting and micronutrient deficiencies in malnourished children. AB - OBJECTIVE: To determine the frequency of stunting and micronutrient deficiencies in malnourished children admitted in a tertiary care hospital. METHODS: It was a cross-sectional study conducted at Paediatric department of Civil Hospital Karachi from January 2007 to December 2008. Patients aged 6 to 60 months, admitted in the ward were assessed for nutritional status and stunting according to the WHO classification of malnutrition, mild (weight for height ratio between 1SD to -2SD) moderate (-2SD TO-3SD) and severe (less than -3SD of NCHS/WHO reference values) malnourished children were included in the study. All the patients were subjected to clinical examination, which included height/length, weight and clinical signs of micronutrient deficiencies. Laboratory investigations were done to confirm the clinical diagnosis of iron deficiency anaemia and rickets. The collected data was analyzed by Statistical Program SPSS version 15. Frequencies and percentages were computed to present all categorical variables. Quantitative variables such as age was presented by mean +/- SD. RESULTS: A total of 150 patients were enrolled in this study. Their mean age was 24.4 +/- 13.8 months (range 6 to 60 months). Of all, 63 (44%) patients were severely stunted, 44 (29%) had moderate stunting, 27 (18%) had mild stunting while only 16 (10.7%) had normal stature. Severely malnourished (< -3SD) were 119 (79%) patients, 30 (20%) patients had moderate malnutrition (-2SD to -3SD). Forty two percent severely malnourished children also had severe stunting. Anaemia was the most common micronutrient deficiency seen in 117 (78%) patients, out of these 88% had iron deficiency anaemia, Rickets was found in 54(36%) patients. Vitamin A deficiency was present in 21 (14%) cases. Other miscellaneous micronutrient deficiencies were zinc and B-complex deficiency in 42 (28%). CONCLUSION: Malnutrition and associated micronutrient deficiencies were frequently found in children between 13 to 24 months of age. Stunting was commonly present between 25 to 36 months of age, it was associated with severe malnutrition in 42% cases. Anaemia is the most common micronutrient deficiency in malnourished patients, it was observed in 78% of cases whereas 44% of severely stunted patients had coexisting rickets. PMID- 20578604 TI - Assessment of differential leukocyte count in patients with acute coronary syndrome. AB - OBJECTIVE: To assess the predictive ability of leukocyte subtypes for mortality in patients with acute coronary syndrome (ACS). METHODS: One hundred and thirty three consecutive patients of ACS wer assessed in the study and were followed up for one year. Diagnosis was based on clinical characteristics and the laboratory data. The total leukocytes and its subtypes were counted by Sysmex automated cell counter. The predictive ability for death of total count of leukocytes, neutrophils, lymphocytes and monocytes was assessed using Cox regression analysis. RESULTS: Univariate analysis revealed higher prevalence of total leukocytes (HR= 1.001, p < or = 0.001) and its subtypes, neutrophils (HR = 1.001, p < or = 0.001) and monocytes (HR 1.006, p < or = 0.001), in patients of ACS. In multivariate modeling, after entering standard coronary risk factors, count of total and differential leukocytes-neutrophils, lymphocytes, monocytes and cardiac biomarkers CK-MB, Trop I; the monocyte count (hazard ratio [HR] 1.004, CI 1.002 1.006, p < 0.0001) was found to be independent predictor for ACS. A significance correlation between monocyte count and CK-MB, representing extent of myocardial damage, was also seen (r = 0.301, p < 0.0001). CONCLUSION: The increase in monocyte count is an independent predictor of death and prognostic marker of the extent of myocardial damage in patients with ACS. PMID- 20578605 TI - An appraisal of Greulich-Pyle Atlas for skeletal age assessment in Pakistan. AB - OBJECTIVE: To assess accurate skeletal age (SA) in clinical and medico-legal decisions using the Greulich-Pyle (GP) atlas and to see its applicability across diverse populations in Karachi. METHODS: Hand-Wrist radiographs obtained at our institution from January 2005 to March 2008, for an indication of trauma, in subjects with chronological age (CA) up to 216 months, were reviewed by two radiologists blinded to CA. Subjects ever investigated for metabolic, growth or nutritional disorders were excluded. SA was assessed according to GP atlas. To establish inter-observer reliability, 100 random radiographs were dually evaluated. Both sexes were divided into four subgroups. For each subgroup, difference between skeletal and chronological age was calculated. (paired t-test, alpha < 0.05). RESULTS: Total 889 radiographs were analyzed. Inter-observer correlation coefficient was 0.992 (p < 0.001). Mean differences of up to 13 months between SA and CA were documented. The differences were statistically significant in all groups except adolescent males. CONCLUSION: Our findings suggest against the applicability of GP atlas for accurate SA assessment in Pakistani children. PMID- 20578606 TI - Home deliveries: reasons and adverse outcomes in women presenting to a tertiary care hospital. AB - OBJECTIVE: To identify the reasons and adverse outcomes of home deliveries in women presenting to a tertiary care hospital. METHODS: A prospective, descriptive study was undertaken in the Department of Obstetrics and Gynaecology, Unit III, Civil Hospital Karachi from 1st April, 2007 to 31st August, 2007. All patients who were admitted with any complication of home delivery during this period were included in the study. Patients and/or their attendants were interviewed to collect data regarding age, parity, sociodemographic characteristics, reasons for home delivery, presenting complaints and complications of home delivery. The data was recorded on structured questionnaires, analyzed by SPSS version 16 and presented as frequencies and percentages. RESULTS: The mean age of patients was 26 +/- 5.3 years and the median parity was 2. The majority of the patients were Urdu-speaking (57.5%) followed by Sindhi (20.3%) and Balochi-speaking (11.9%). Eighty-seven percent of women had received either no or just primary education. The two most frequent reasons quoted for home deliveries were family tradition in 190 (72.8%) and lack of affordability in 179 women (68.6%). Postpartum haemorrhage was the main adverse outcome in 132 women (50.6%) followed by retained placenta/placental pieces in 74 women (28.4%). CONCLUSION: The main reasons for having a home delivery are family tradition and poor socioeconomic condition of the family and the most important adverse outcomes of home delivery are postpartum haemorrhage and retained placental tissue. PMID- 20578608 TI - Perception of community regarding common diseases prevailing in the a squatter settlement of Karachi, Pakistan. AB - OBJECTIVE: To determine the perceptions of the community about prevalence of different diseases in Gulshan-e-Sikandarabad, an urban squatter settlement in Karachi and compare them with the data about disease pattern available at Primary Health Care Center in the same community. METHODS: A stratified random sample of ten percent of houses of the community was selected and both male and female heads of household were interviewed. Open ended questionnaire was used to record perceptions of responders. A total of 336 persons were interviewed out of which 196 (58%) were females and 140 (42%) were males. RESULTS: Age, education, nationality and ethnicity (Sikandarabad has inhabitants from Afghanistan as well. In our study 12 were Afghan nationals. Among Pakistani responders majority were Pathans, some were Punjabi, Saraiki etc.) had no statistically significant difference in responses. Gender had the most significant difference in responses. The perceived nine top most common diseases were similar to the top nine common diseases according to data of the health center of Ziauddin University located in Gulshan-e-Sikandarabad. CONCLUSION: The perceptions of community members about most of the common diseases prevalent in their community was similar to the disease pattern maintained at Primary Health Care center in the same locality. Anaemia and helminth infestation although common according to the health center record were not perceived as common by the community members. PMID- 20578607 TI - Does the added benefit of ondansetron over dexamethasone, to control post operative nausea and vomiting, justify the added cost in patients undergoing tonsillectomy and adenotonsillectomy? AB - OBJECTIVE: To investigate comparative effectiveness of ondansteron and dexamethasone in prophylaxis of PONV in tonsillectomy and adenotonsillectomy patients. METHODS: The study was conducted at Shifa International Hospital Islamabad from 1st January to 30th June 2009, on 60 patients undergoing tonsillectomy or adenotonsillectomy, with their consent. After consecutive alternate sampling, patients were divided into two groups containing 30 patients each. Ondansteron was given in one group, and Dexamethasone in the other group, as anti emetic, at the time of induction. Episodes of PONV were recorded at three specified intervals, i.e., immediate postoperative, 6 hours after surgery and 12 hours after surgery. Data was entered on a pre-designed performa. The data was analyzed in SPSS Version 13.0. RESULTS: Ondansteron Group had a mean age of 12.7 +/- 9.54 years (5-36 years). There were 22 (73.3%) males and 8 (26.7%) females. Dexamethasone Group had a mean age of 14.8 +/- 8.4 years (5-35 years) of whom 18 (60.0%) were males and 12 (40.0%) were females. Overall 6 patients who received ondansetron had PONV compared to 7 patients in the dexamethasone group. This difference was statistically insignificant (p > 0.05). CONCLUSION: Dexamethasone was equally effective in controlling PONV in tonsillectomy and adenotonsillectomy patients. The improved benefit of using ondansetron over dexamethasone, on a regular basis, does not justify the added cost. PMID- 20578609 TI - Is it possible to reduce rates of placenta praevia? AB - OBJECTIVE: To determine factors responsible for rising rates of placenta praevia. METHODS: This comparative study was performed at Jinnah Post Graduate Medical Centre Karachi, (Group-A) from September 2000 to February 2002 and (Group-B) from January 2008 to January 2009. All women with major degree of placenta praevia diagnosed on ultrasound who came in emergency or through out patient department were included in the study. Patients with mild degree of placenta praevia were excluded. Group A had 100 patients and Group B, 58 patients. Chi-Squire test was used for comparison of previous study and current study. RESULTS: The number of unbooked cases in both groups A and B was high (A=76%, B=62%). Most patients were grandmultipara (A=41%, B=34%) with ages ranging from 31-35 years (A=36%, B=43%). Even primigravida had a major degree of placenta praevia (A=17%, B=7%). There was a significant difference in two groups in term of previous caesarean section (A=12%, B=38%). Association of placenta praevia following miscarriages was also noted (A=41%, B=29%). Placenta accrete were noted in two cases in group B, both required obstetrical hysterectomies. The results revealed a favourable foetal out come in both groups, A= 93 (93%), B=55 (95%). CONCLUSION: With rising rate of previous caesarean sections over an eight year period from 12% to 38% the frequency of placenta praevia has increased. Most patients continue to present as unbooked cases in emergency, there fore the associated morbidity due to haemorrhage remains high. Therefore efforts should be made to avoid primary caesarean section where possible. In addition antenatal care and timely diagnosis of placenta praevia on ultrasound can decrease the associated morbidity. PMID- 20578610 TI - Assessment of clonidine effect as premedicative drug on kidney function. AB - OBJECTIVE: To assess the effect of oral clonidine as a premedicative drug on 24 hour urine output, urine specific gravity, plasma renin activity as well as serum and urine electrolytes levels. METHODS: This prospective study was carried out on 60 women aged 20-40 years old undergoing repair of cystocoele-rectocoele perineorraphy under general anaesthesia in Asali Hospital in 2004 in Khorramabad, Iran. Subjects were randomly divided into two equal groups of 30 each. Group I and group II received clonidine tablet at the dose of 5 microg/kg and placebo tablet, respectively, 90 minutes before induction of general anesthesia. In this study, blood and urine samples were taken for laboratory measurements prior as well as 6 hours after taking the tablets. Differences between the two groups were compared through Mann-Whitney u-test, chi2 test and t-student test. P-value < 0.05 was considered statistically significant. RESULTS: There were no significant changes before and after receiving tablets in urine and blood Na and K as well as urine specific gravity in group II (P > 0.05). Group I had higher urine Na and K level (P = 0.001), however, no differences had been shown in blood Na and K level (P > 0.05). Urine specific gravity was lower in group I after receiving tablet (P < 0.009). A significant increase in 24-hour urine output (P = 0.001) and a marked decrease in plasma renin activity was seen in group I (P = 0.001). CONCLUSION: This study suggests that clonidine is a safe premedicative drug in anaesthesia and does not change the serum electrolytes levels. PMID- 20578611 TI - Craniocerebral aspergillosis: a review of advances in diagnosis and management. AB - Craniocerebral aspergillosis is a rare but dangerous central nervous system infection. The infection has a spectrum of presenting features, mostly affecting immunocompromised individuals. The incidence appears to be on the rise that has been especially observed in the immunocompetent population. A high index of suspicion, a comprehensive understanding of the infectious process and advanced laboratory and radiological diagnostic techniques, allow early diagnosis. Surgery, followed by systemic antifungal medications, remains the cornerstone of management. Early administration of empirical anti-fungal agents along with immunomodulators may further improve prognosis. Immunocompetent patients tend to have better outcomes as compared to those who are immunocompromised. Patients with intradural disease carry the worst prognosis. PMID- 20578612 TI - Zinc and copper levels in hydatid cyst fluid and patient's blood. AB - Eighteen patients with hydatid disease from Basrah General Hospital were involved in the study during 2007. Their ages ranged from 23-56 years with mean of 33.55 +/- 10.4 years. The control group consisted of 25 apparantly healthy individuals. Zinc and copper levels in the sera and hydatid fluids were estimated by atomic absorption spectrophotometer. Mean values of zinc and copper concentrations in sera of patients were 124.33 +/- 30.04 mg/dl and 88.05 +/- 15.91 mg/dl respectively in comparing with those of the control group (P < 0.0001). On the other hand, mean values of both zinc and copper levels in sera of patients were lower than those of the hydatid cyst fluids which were statistically significant. There was a positive correlation between sera zinc and copper concentrations of patients and the control group while negative correlations were observed with other relationships. PMID- 20578613 TI - Anaesthetic management of two patients with beta-thalassaemia intermedia. AB - There is paucity of literature regarding the anaesthetic management of patients with thalassaemia intermedia. In this case study, the anaesthetic management and concerns in two children with thalassaemia intermedia aged eleven and nine years undergoing herniotomy and splenectomy respectively is reported. Both children had unanticipated difficulty in airway management and high intraoperative blood pressure trends. These cases are representative of the range of problems seen in children with thalassaemia intermedia. PMID- 20578614 TI - Late onset postpneumonectomy empyema presenting 24 years after pneumonectomy. AB - Empyema is a devastating complication that is rarely seen in the postpneumonectomy setting. A 56-year-old man presented to us 24 years after pneumonectomy with a 15 days history of chest pain and shortness of breath. Physical examination revealed a fluctuant swelling at the thoracotomy site. Computed tomography scan showed a large fluid density mass in the left pneumonectomy space. Needle aspiration and video assisted thoracoscopic surgery was carried out and culture of the aspirated fluid grew Pseudomonas aeruginosa. The patient was discharged with the chest tubes in place. At 2 months follow-up, the patient presented with fever and continuous copious drainage of pus from empyema tubes. Piperacillin with tazobactam at 4.5 grams per day helped in the resolution of fever but the output from the empyema tubes continued. An open window thoracostomy was performed and the patient was discharged on standard dosage of cefixime and fusidic acid. Following this antibiotic regimen, he remained stable with complete resolution of the infection. PMID- 20578615 TI - Recurrent intracranial haemangiopericytoma compatible to synovial sarcoma. AB - A rare case of intracranial haemangiopericytoma with a thrice recurrence, treated by gross total removal and local irradiation is presented. Histological examination of the tumour specimen showed haemangiopericytoma (WHO grading III). The tumour has not recurred for 15 months after third operation and 30 sessions of radiotherapy, although the effectiveness of radiation for haemangiopericytoma is unclear. PMID- 20578616 TI - Multiple chest wall tuberculous abscesses. AB - Tuberculosis (TB) usually involves the lungs and hilar lymph nodes. Musculoskeletal TB occurs in 1%-3% of patients with TB, while chest wall TB constitutes 1%-5% of all cases of musculoskeletal TB. The present case reports a twenty six year old immunocompetent patient with multiple chest wall tuberculous abscesses along with multiple ribs destruction, in absence of active pulmonary TB or intrathoracic lymphadenopathy. Chest wall TB though rare, should have a high degree of suspicion in multiple destructive bone lesions, especially in patients from regions where TB is endemic. Plain chest x-ray postero-anterior (CXR-PA) view revealed osteolytic rib lesions with overlying opacities; fine needle aspiration cytology (FNAC) was not helpful. Computerized tomography (CT) of thorax and histopathology of the biopsied unhealthy tissue from the cavity were consistent with the diagnosis of TB. Oral antitubercular therapy (ATI) was given for 12 months, following which the chest wall abscesses and rib lesions healed. PMID- 20578617 TI - Hypercalciuria and nephrolithiasis on long-term follow-up of pseudo-vitamin D deficiency rickets. AB - A case of pseudovitamin D deficiency (Vitamin D dependent rickets type I) is presented, who initially responded to physiological doses of calcitriol but developed nephrolithiasis and hypercalciuria around puberty. Hypercalciuria was corrected after stopping calcitriol. Pseudo vitamin D deficiency rickets also called vitamin D dependent rickets type I (VDDR 1) is an uncommon cause of rickets. Patients appear normal at birth and manifests with signs between the ages of two months to two years. Muscle weakness is prominent, radiographic features are striking and response to calciferols is complete. Hypercalciuria and nephrolithiasis are uncommon in the untreated disease but can develop due to overtreatment with calcitriol or oral calcium. Here we report a patient who developed hypercalciuria and nephrolithiasis around puberty while on maintenance dose of calcitriol and oral calcium. PMID- 20578618 TI - Successful transradial percutaneous coronary intervention with radial artery anomaly. AB - The transradial approach as an access for percutaneous coronary intervention (PCI) has been widely adopted. However, anatomical variations and stenoses may pose significant challenges to the operator. We report a case of successful transradial PCI in a patient with a complete radioulnar loop. PMID- 20578619 TI - Improving schizophrenia diagnosis through biomarkers: an upcoming prospect. PMID- 20578620 TI - Effects of a perindopril-based blood-pressure-lowering regimen in patients with previous stroke or transient ischaemic attack (progress). How do the results affect practice in Pakistan? PMID- 20578621 TI - Carcinoma of unknown primary. PMID- 20578622 TI - Needle stick injuries and medical education. PMID- 20578623 TI - An unusual foreign body: a pendant. PMID- 20578624 TI - Association of passive smoking with respiratory symptoms and clinical correlates, among married women, in a rural community in Islamabad. AB - OBJECTIVE: To investigate the association of passive smoking with respiratory symptoms and clinical correlates in married women in a rural area of Pakistan. METHOD: A Cross-sectional study was carried out on married women of Nurpur Shahan (rural Islamabad) by means of an Interviewer administered questionnaire. Systematic sampling of households was done. A total of 296 women were surveyed. The study period extended from January to July 2009. All data was entered and analyzed using SPSS v 10.0. RESULTS: The two major respiratory symptoms that were found to be associated with passive smoking were sinusitis [adjusted O.R(95% CI) 2.2 (1.3 - 3.5), p = 0.001] and cough [adjusted O.R (95% CI) 2.4 (1.2 - 4.8), p = 0.017]. Wood used as fuel for cooking purposes also contributed to one of the symptoms such as headache (p = 0.007). The pulse rate (79 +/- 11 beats/min) of the passive smoking women was statistically significantly higher than the pulse rate (76 +/- 9 beats/min) of the non-passive smoking women (p = 0.012). CONCLUSION: Passive smoking was found to be associated with respiratory symptoms among married women in this study. Higher pulse rate was associated with passive smoking. PMID- 20578625 TI - Giant unresectable lymphangioma of the trunk managed via intra-tumour injections of bleomycin. AB - Surgical excision was once considered the mainstay of treatment for lymphangiomas. However, that paradigm is now changing with sclerotherapy emerging as a viable alternative. A 22-year-old girl presented with a mucopurulent and painful discharge from an extensive wound in the trunk. Chest roentogram showed a large soft tissue abnormality with multiple calcifications in the right upper abdomen and lower thorax. Magnetic resonance imaging revealed an extensive lobulated mass measuring 27 x 19 cm. Due to the extensive involvement of tissues, surgical excision did not appear to be a favourable option in this case. Local injections of bleomycin were successfully administered; resulting in complete regression of the lesion. There has been no recurrence at 2 years of follow up. Use of bleomycin sclerotherapy appears to be a safe and effective management strategy and obviates the need for primary surgery especially in extensive lymphangiomas. PMID- 20578627 TI - Extracorporeal photopheresis for graft versus host disease: a hope. PMID- 20578626 TI - Microbes fight for survival, are we aware of the danger? PMID- 20578628 TI - Recurrent urinary tract infection in women: can cranberry prevent it? PMID- 20578630 TI - Patient opinion divided on the introduction of single rooms. PMID- 20578631 TI - Into the rhythm. Interview by Alison Handley. AB - With more than two million people in the U.K. having an arrhythmia, a campaign is raising awareness of the importance of pulse taking. PMID- 20578632 TI - Pushing the boundaries. Interview by Lynne Pearce. AB - A nurse-led cardiology unit has proved to be a success with health professionals and the community it serves. PMID- 20578633 TI - A vision for children. Interview by Anita Pati. AB - The opening of a paediatric assessment and decision area (Panda) unit at Salford A&E means sick children and their families do not have to be transfered to other hospitals for treatment. PMID- 20578634 TI - Twice the talent. Interview by Ingrid Torjesen. AB - Twin brothers Wilf and Rob McSherry are both professors of nursing--but got there in different ways. PMID- 20578636 TI - Prove yourself. PMID- 20578635 TI - When is it right to wear the cross? PMID- 20578638 TI - Nurses' views on challenging doctors' practice in an acute hospital. AB - AIM: To explore the extent to which nurses are willing to challenge doctors' practice in everyday situations in an acute NHS hospital. METHOD: Qualitative data were collected using in-depth interviews with 12 nurses in an acute NHS hospital in England. FINDINGS: Participants believed that they challenged doctors' practice and acted as patients' advocates. However, data revealed that nurses questioned doctors' practice only under specific circumstances. Nurses would not challenge doctors if they perceived that this would result in conflict or stress, if they were afraid of the doctor or feared reprisal. CONCLUSION: Nurses are discouraged from challenging doctors' practice by the structural inequality arising from the gender division of labour and doctors' expert knowledge and status (medical dominance) in the workplace. PMID- 20578637 TI - Leadership skills for nurses working in the criminal justice system. AB - This article, the second in a five-part series, explores leadership skills for nurses working in the criminal justice system to effect change in service provision. The article discusses different leadership styles and distinguishes management from leadership. Factors that influence change are outlined, as is the need for emotional intelligence, teamwork and collaborative working. Change management, negotiating ability and conflict management are important skills that nurses should develop to become effective leaders. PMID- 20578639 TI - Carbon monoxide poisoning. AB - This article focuses on the causes, diagnosis and management of carbonr monoxide poisoning. It describes assessment strategies and treatment options for the patient with potential carbon monoxide poisoning. PMID- 20578640 TI - Communicating bad news. PMID- 20578641 TI - Support for research. PMID- 20578642 TI - The care revolution. PMID- 20578643 TI - Does osteoarthritis of the knee also have a psychogenic component? Psycho emotional treatment with a radio-electric device vs. intra-articular injection of sodium hyaluronate: an open-label, naturalistic study. AB - This study is to compare, in patients suffering of knee joint disorder, the effects of intra-articular injection of Sodium Hyaluronate, and those of a treatment aiming at the improvement of the emotional status carried out by means of a Radio Electric Device (REAC). 30 subjects were divided into two groups: 15 who preferred a non-drugs approach (Group A) and 15 who preferred an infiltrative treatment (Group B). The evaluations were expressed for both pain level and knee bending and extension. Group A showed significant decrease in pain, stiffness, joint noises and intra-articular effusion, and significant improvement in motion range, without any patients worsening. 8 patients showed complete disappearance of pain in Visual Analog Pain Scale (VAS) evaluation, evident by a level of 0. The initial VAS results were between 8 and 4. One month after treatment's end, VAS results of the patients in Group A were between 3 and 0. Group B showed significant decrease in pain, stiffness, joint noises and intra-articular effusion, but no significant improvement in motion range; 2 of 15 patients showed worsening symptoms and no significant improvement in muscular hypotrophy. Initial VAS results were between 7 and 4. One month after treatment's end, VAS results were between 6 and 0. PMID- 20578644 TI - Efficacy of acupunture in patients with chronic neck pain--a randomised, sham controlled trial. AB - The aim of this study was to compare the efficacy of electroacupuncture and sham acupuncture in the treatment of patients with chronic neck pain. 31 patients with chronic neck pain were included in a randomised, controlled trial. Electric stimulation was given for 30 minutes at low frequency (1-4Hz), pulse width of 200 micros, interrupted wave form. Of the 29 patients who completed the therapy, 13 were assigned to conventional acupuncture and 16 to sham acupuncture groups, receiving 3 sessions a week for a total of 10 sessions, each lasting for 30 minutes. Patients were evaluated before and after therapy and 3 months later by Visual Analogue Scale (VAS) and the bodily pain subscale of the Short Form Health Survey-36 scale. The treating physician was different from the evaluating physician who, like the patient, was blinded. VAS scores in both groups significantly reduced after therapy and at 3 months post-therapy, but the difference between groups was not significant. In respect of bodily pain, there was a significant improvement in the acupuncture group after therapy (P<0.01). Stimulation of conventional acupuncture points was not generally superior to needling ofnonspecific points on the neck, and both treatments were associated with improvement of symptoms. Needles inserted into the neck are likely to be an inappropriate sham control for acupuncture. PMID- 20578645 TI - The effects of electro-acupuncturing DU26 (renzhong) on motor cortical excitability and neurofunction after focal cerebral ischemia injury in rats. AB - OBJECTIVE: To study the effects of electro-acupuncturing DU26 (Renzhong) on cortical excitability and neurofunction after focal cerebral ischemia injury. METHOD: 30 male Wistar rats were divided randomly into control group, MCAo group and MCAo+DU26ES group, 10 in each group. Middle Cerebral Artery occlusion models (MCAo) were created in accordance with Zea Longa method and modified method. DC continuous square-wave electric pulse stimuli (2Hz, 3mA) which was given between DU26 and non-acupoint area in the left shoulder, was applied to MCAo+DU26ES group 10 minutes every time, twice a day, while the control group and MCAo group received no treatment. 3 days later transcranial electrical stimulation motor evoked potential (MEP) was recorded, the onset latency and peak-to-peak amplitude were analyzed and the neurological deficits were evaluated. The effects of electro-acupuncturing DU26 (Renzhong) and MCAo injury on these parameters were analyzed. RESULTS: Given the isointensity suprathreshold stimulus, the latency on the affected side in MCAo group was significantly longer than that in control group (P<0.05), the amplitudes on both sides were significantly reduced (P<0.05, P<0.05); the latencies on both sides in MCAo+DU26ES group tended to become shorter and the amplitudes on both sides tended to increase compared with MCAo group; there were no significant differences on latency and amplitude between the healthy side and the affected side in all groups (P>0.05). The neuro-scores of rats receiving electro-acupuncturing DU26 (Renzhong) were significantly higher than those in MCAo group (P<0.05). CONCLUSION: Electro-acupuncturing DU26 (Renzhong) can improve the motor cortical excitability, and facilitate the motor function recovery after MCAo injury. PMID- 20578646 TI - Metal ring on 4th or 5th finger markedly increases both cardiac troponin I at left ventricle and cancer-related parameters such as oncogen C-fosAb2 & integrin alpha5beta1[corrected] by 4-12 times. Thus these metal rings appear to promote both heart problems & cancer. AB - We examined patients wearing a metal ring on the left 4th finger with abnormally increased Cardiac Troponin I (which is known to increase in the presence of myocardial injury or left ventricular hypertrophy) of 5-14ng BDORT units (depending on the ring and individual) at left ventricle compared with normal value of 1ng BDORT units or less. Although shape of the ECG does not change significantly regardless of whether metal rings are on or not, when rings are on, the Bi-Digital O-Ring Test evaluation of trace of ECG revealed "Vulnerable Period of Rising Part of T-wave" of ECG waves (which correspond to the left ventricle and AV node) become abnormal with increased Cardiac Troponin I. DHEA in various parts of the body reduced significantly and maximum decrease in DHEA was found when metal ring was on the left 4th and 5th fingers. Telomere reduced with each of the 5 fingers, but the 2nd, 4th, and 5th fingers produced the maximum reduction of telomere. When metal ring was inserted onto the left 1st finger and left 2nd finger, Cardiac Troponin I did not change significantly. Additional abnormality was found when patients with cancer wore metal ring(s); namely both Cardiac Troponin I and cancer parameters, such as Integrin alpha5beta1[corrected] and Oncogen C-fos Ab2, increase anywhere between 4-12 times. However, when the ring was cut, creating a 1mm or longer empty space, no increase in cancer markers and Cardiac Troponin I were observed. Similar findings were found with metal bracelets. PMID- 20578647 TI - Evaluation of methane-utilising bacteria products as feed ingredients for monogastric animals. AB - Bacterial proteins represent a potential future nutrient source for monogastric animal production because they can be grown rapidly on substrates with minimum dependence on soil, water, and climate conditions. This review summarises the current knowledge on methane-utilising bacteria as feed ingredients for animals. We present results from earlier work and recent findings concerning bacterial protein, including the production process, chemical composition, effects on nutrient digestibility, metabolism, and growth performance in several monogastric species, including pigs, broiler chickens, mink (Mustela vison), fox (Alopex lagopus), Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), and Atlantic halibut (Hippoglossus hippoglossus). It is concluded that bacterial meal (BM) derived from natural gas fermentation, utilising a bacteria culture containing mainly the methanotroph Methylococcus capsulatus (Bath), is a promising source of protein based on criteria such as amino acid composition, digestibility, and animal performance and health. Future research challenges include modified downstream processing to produce value-added products, and improved understanding of factors contributing to nutrient availability and animal performance. PMID- 20578648 TI - Investigations on the kinetics of the concentration of deoxynivalenol (DON) and on spoilage by moulds and yeasts of wheat grain preserved with sodium metabisulfite (Na2S2O5, SBS) and propionic acid at various moisture contents. AB - Unground wheat kernels contaminated with 2.09 mg deoxynivalenol (DON) per kg dry matter were stored for up to 56 days at moisture contents of 15, 17.5 and 20% to study the alterations of DON concentration when the wheat was stored either unsupplemented or supplemented with 5 g sodium metabisulfite (Na2S2O5, SBS), 10 g propionic acid (PA) or 5 g SBS plus 10 g PA per kg. SBS addition alone or in combination with PA reduced the DON contamination to 1.2-4.3% of the initial DON concentration while DON concentration of unsupplemented and wheat batches supplemented only with PA varied inconsistently or remained unchanged. The SBS related DON reduction was paralleled by a concomitant increase in the concentration of the non-toxic reaction product DON sulfonate. In contrast to the unsupplemented wet-stored controls, SBS addition prevented the growth of moulds and yeasts when added alone or in combination with PA. In conclusion, for the conditions examined, the wet preservation of DON-contaminated wheat with SBS seems to be promising as an on-farm detoxification measure. PMID- 20578649 TI - Effects of ensiling on in situ ruminal degradability and intestinal digestibility of corn forage. AB - The effective degradability of dry matter (DM), crude protein (CP) and amino acids (AA), and the intestinal effective digestibility (IED) of DM and CP of a green forage corn (GC) and its silage (EC) were determined on freeze-dried samples using three rumen and duodenum cannulated wethers. Two rumen incubations with duplicate bags were performed for each feed. Rumen degradation was determined on one series of bags from each incubation. The other series was freeze-dried and used to determine IED using mobile nylon bags. Microbial contamination of rumen incubated residues (determined with 15N techniques) fitted exponential functions, which showed a greater microbial contribution in EC than in GC in the undegradable DM (18.6% vs. 13.5%) and CP (81.7% vs. 69.4%). Degradability was calculated considering the particle rumen outflow rate (k(p): 0.056/h) of the EC (EDp) or additionally the rate of comminution and mixing (kr: 0.130/h) of these particles (EDep). Ensiling increased EDp (9.33%, p < 0.01) or EDcp (5.30%, p = 0.062) of DM and was associated with losses of nitrogen and with large changes in the AA profile. It is necessary to correct the microbial contamination, because it represents 32.0% (GC) and 42.5% (EC) of the undegraded CP when using k(p) and k(c). Ensiling caused higher degradabilities for some AA as well as large differences in the changes due to the rumen fermentation on the AA profile. However, it had only limited effects on the undegraded protein profile. Ensiling also reduced the IED of DM (23.3% vs. 14.6%; p = 0.057). In conclusion, results do not show losses of nutritive value by ensiling corn cut at vitreous grain stage. PMID- 20578650 TI - Effect of exogenous fibrolytic enzymes on ruminal fermentation and nutrient digestion in dairy cows. AB - The aim of the present study was to examine the effects of an exogenous fibrolytic enzyme product applied to a total mixed ration (TMR) prior to feeding on ruminal fermentation, microbial protein synthesis, nutrient digestion, and milk yield and composition. Six multiparous lactating Holstein cows (598 +/- 29 kg initial live weight and 98 +/- 30 days in milk) fitted with rumen and duodenal cannulae were allocated to two treatments in a crossover design over three consecutive 28-d periods. The TMR containing 50% concentrates, 30% corn silage and 20% grass silage on dry matter (DM) basis, was mixed once daily and fed twice a day. Treatments were TMR alone (Control) or TMR with an enzyme product containing primarily cellulase and xylanase activities (9000 U endo-1,4-beta glucanase, 24000 U endo-1,3(4)-beta glucanase and 40000 U 1,4-beta xylanase per ml). The enzyme product was applied at a rate of 6.2 ml/kg TMR (DM basis). It was diluted at a rate of 1:5 with water and applied daily to the TMR. During the control period the cows received a TMR supplemented with 36 ml water/kg TMR on DM basis. Duodenal digesta flow was measured using Cr2O3 as flow marker and microbial protein in the duodenal digesta was estimated by near-infrared spectroscopy (NIRS). There were no significant differences in ruminal pH-values, NH3-N concentrations, total SCFA concentrations and molar proportions of SCFA. No treatment effects on microbial N flow to the duodenum and efficiency of microbial protein synthesis were observed. The apparent ruminal digestibilities of DM, organic matter, NDF and ADF, milk yield and composition were also not affected by the enzyme supplementation. In this study the application of exogenous fibrolytic enzymes fed to dairy cows did not show a significant effect on any parameter tested. PMID- 20578651 TI - Digestibility and energy value of cereal-based diets in relation to digesta viscosity and retention time in turkeys and chickens at different ages estimated with different markers. AB - Digesta viscosity, ileal transit time of digesta, apparent ileal protein digestibility and apparent metabolisable energy (AME(N)) of diets based on wheat and dehulled barley (WB), oats (O) or a mixture of these (WBO) fed as such or with enzyme supplementation in three- and six-week old turkeys and broilers were investigated. In addition, differences between ileal digestibility and AME(N) calculated by using titanium dioxide (TiO2), chromic oxide (Cr2O3) or acid insoluble ash (AIA) as indigestible markers were compared. Digesta viscosities were generally moderate reaching from 2.5 mPa x s to 7.3 mPa x s. The highest viscosities were observed in WBO diets. Viscosities were reduced with age in broilers, and were generally higher in turkeys than in broilers, especially at six weeks of age. Digesta retention time in ileum was elongated with age of the birds, pronouncedly in broilers. Oat inclusion to the diets decreased retention time especially in broilers at six weeks of age. Apparent ileal digestibility of protein ranged from 0.64-0.83, was lower at six weeks of age than at three weeks of age and generally lowest in O diets, especially in turkeys. AME(N) of the diets ranged from 11.2-13.4 MJ/kg being higher at six weeks of age than at three weeks of age. AME(N) of Diets O was the lowest but AME(N) of WBO diets was higher than that of WB diets indicating a synergistic interaction of cereals, this trend being more pronounced in broilers. Enzyme supplementation decreased viscosity and improved AME(N) in most diets, but did not affect ileal protein digestibility. Differences between ileal digestibility estimates obtained with TiO2 or Cr2O3 were small and mainly not significantly different from 0. AME(N) estimates were generally higher when calculated with Cr2O3 than with TiO2. AIA gave remarkably lower AME(N) values than TiO2 (the significant differences ranging from 0.24-0.94 MJ/kg). In addition, effects of markers on AME(N) estimates interacted with age of the birds and dietary treatments. PMID- 20578653 TI - An unusual accident during a primary molar extraction. AB - BACKGROUND: Special care must be taken during surgical procedures in children, especially primary tooth extractions. However, despite dentist's effort to perform tooth removal carefully, some accidents may be unavoidable when defective instruments are unknowingly used. CASE REPORT: This article presents a case of a pediatric dental elevator fracture during a primary mandibular right second molar extraction. CONCLUSION: Although uncommon, instruments breakage may occur during dental and surgical procedures. Therefore, dentists should always check the surgical instrument for signs of breakage and be prepared to solve a possible emergency. PMID- 20578652 TI - The effects of lipoic acid on soybean beta-conglycinin-induced anaphylactic reactions in a rat model. AB - The purpose of this study was to evaluate the effects of feeding a low dose of lipoic acid on attenuating soybean beta-conglycinin-induced hypersensitivity using a rat model, with ovalbumin as the positive allergic control. Forty-eight recently weaned male Sprague-Dawley rats were assigned to four treatments and fed a cornstarch-casein-based diet either unsupplemented (Groups I, II and III) or supplemented with 25 mg/kg lipoic acid (Group IV). On days 1, 10, 17, and 24, Groups III and IV were sensitised with 20 mg beta-conglycinin by means of intragastric gavage, while Group II was sensitised with 20 mg ovalbumin and Group I (control) with casein. On day 31, rats received a double dose of beta conglycinin, ovalbumin or casein, respectively. Ovalbumin-sensitised rats (Group II) and beta-conglycinin-sensitised rats (Group III) demonstrated an increase in serum IgE and histamine release, but reduced growth performance compared to the control (Group 1) (p < 0.05). A low dose of lipoic acid had no effect on average weight gain, but increased villus height in the jejunum (p < 0.05), while reducing serum beta-conglycinin-specific IgE and histamine content in the jejunum. Moreover, lipoic acid supplementation did not significantly affect interferon-gamma or interleukin-4. Taken together, our results suggest that a low dose of lipoic acid could potentially be used as an immunomodulator to attenuate soybean beta-conglycinin induced allergies. PMID- 20578654 TI - Apexification with MTA using internal matrix: report of 2 cases. AB - Calcium hydroxide (CH) has been reported to have several drawbacks when used for apexification. Mineral Trioxide Aggregate (MTA) has generated considerable interest as an alternative. Two different cases are reported using MTA for apexification. In the first case an incomplete CH barrier was used as a matrix against which MTA could be condensed. In the second case internal matrix was formed using absorbable collagen sponge and a comparable result could be achieved. Further studies are needed to develop it into a standardized method, akin to that of matrices used in class II restoration. PMID- 20578655 TI - Teething symptoms in the first year of life and associated factors: a cohort study. AB - OBJECTIVE: To investigate the occurrence and management of teething symptoms during the first year of life and associated factors. STUDY DESIGN: 500 children were recruited at birth. Research assessments including structured interviews, anthropometric measurements and dental examination were carried out after birth, at 6 months and at one-year of age. The primary outcome of this study was defined as the occurrence of one or more teething symptoms within the first year of life, as reported by the mother. RESULTS: Teething symptoms were reported in 73% of the children analyzed (273/375). The symptoms most frequently reported were irritability (40.5%), fever (38.9%), diarrhoea (36.0%) and itching (33.6%). Dentists had little influence on the management of symptoms and self-medication to relieve them was a common practice. The risk of reporting teething symptoms was higher for children from nuclear families (p = 0.040) and for children from families with higher income (p = 0.040). CONCLUSIONS: Teething symptoms were highly reported in this population. Pediatric dentists should be accessible and provide adequate orientation when symptoms can be managed at home or immediate referral to health services when more serious diseases are suspected. PMID- 20578656 TI - Medicine use in children: a critical area. AB - Children are particularly a challenging group of patients when trying to ensure the safe use of medicines. Their variable weight, body surface area and organ system maturity affect their ability to metabolize and excrete medications. In addition, there are few standardized dosing regimens for children, with most medication dosing requiring body weight calculations. These challenges in pediatric medication use contribute to an increased risk of medication errors including serious drug dosing errors. This manuscript addresses the pediatric dentists to focus on the issues related to pediatric medication. PMID- 20578657 TI - Oral health status of the visually impaired children--a south Indian study. AB - Oral health is an important aspect of health for all children, and is all the more important for children with special health needs. The oral health of children who are visually impaired can be disadvantaged, since they are often unable to adequately apply the techniques necessary to control plaque. PURPOSE: The purpose of the present study was to evaluate the oral health status of visually impaired children. METHOD: A modified WHO oral health assessment form was used to assess oral conditions, oral hygiene status, caries experience and gingival status. RESULTS AND CONCLUSION: The children exhibited suboptimal levels of oral health with majority of the children showing a high caries prevalence as well as moderate to severe gingivitis. PMID- 20578658 TI - A comparative study of children's pain reactions and perceptions to AMSA injection using CCLAD versus traditional injections. AB - Pain control is an important part of dentistry, particularly in pediatric dentistry. Recently, a computer-controlled local anesthetic delivery system (CCLAD) has been developed to reduce pain related to the local anesthetic injection. In conjunction with this technology, a new approach to the anterior and middle superior alveolar nerves (AMSA) has been induced. Studies evaluating the CCLAD in pediatric dentistry showed variable results regarding its use in pediatric dentistry. Further evaluation of this technique is needed to provide sound scientific evidence on the use of the CCLAD at this specific injection site in children. AIM: To assess children's pain reactions and pain perceptions of the AMSA injection using the CCLAD compared to the traditional buccal/palatal injections. MATERIALS AND METHODS: Children's pain reactions and perceptions to both techniques were measured in a group of 40 children who received both anesthetic techniques alternatively on two visits. The pain reactions were scored using the SEM scale, whereas the pain perception was evaluated by the Eland color scale. Statistical analysis was carried out using SPSS version 10.0. RESULTS: The AMSA injection delivered with the CCLAD had significantly lower mean pain reaction scores compared to traditional buccal and palatal injections. The prolonged injection time required for delivering the CCLAD injection had no negative impact on the children. The children's pain perception scores when using the CCLAD were also significantly lower compared to the traditional injection. CONCLUSION: The AMSA injection delivered with the CCLAD was found to be a promising device, and had significantly lower pain reaction and perception scores compared to the traditional buccal and palatal injections. PMID- 20578659 TI - Repairing collagen in dentin carious lesions. Influence of sealing the material: a morphometric study. AB - OBJECTIVE: The aim of the present work was to morphometrically evaluate collagen in carious lesions sealed with calcium hydroxide, adhesive systems, glass ionomer cement, and an antibacterial cement. STUDY DESIGN: Samples of infected and affected dentin were stained with Sirius Red (SR). The areas intensively stained with SR were delimited, and the percentage of these areas was measured by blind calibrated examiners. The mean results were subjected to the Kruskal-Wallis test. RESULTS: The affected dentin sealed with Ca(OH)2 showed a better organization of the collagen in relation to the adhesive systems Prime & Bond (p = .0159) and Adhese (p < 0.0001). The affected dentin sealed with Prime & Bond promoted better increase of organized collagen areas in relation to Adhese (p = 0.0004). The infected dentin sealed with glass ionomer cement (p = 0.0018) or antibacterial cement (p = 0.0004) brought a significant increase in the organized collagen areas. CONCLUSIONS: Ca(OH)2 is indicated to seal affected dentin and glass ionomer cement and antibacterial cement may be used for treatment of infected dentin. The addition of antibiotics did not influence the restoration of the infected dentin. PMID- 20578660 TI - Mineral content removal after Papacarie application in primary teeth: a quantitative analysis. AB - The aim of this study was to quantify the mineral content removed from primary teeth after using a chemomechanical system, called Papacarie. MATERIALS: Twenty human primary extracted molars were divided into two groups of 10 specimens each. Group A presented sound molars and Group B decayed molars on the occlusal or occlusal-proximal surface. In Group A, cavities in enamel and dentin with high speed drills were made before treatment. All teeth were treated with Papacarie following the manufacturer's instructions. Each cavity was filled in with the product, allowing curing for 45 seconds, and then removed with the non-cutting edge of the curette. The collected material was sent for laboratory analysis using atomic absorption spectrophotometry technique. Medians for each group were calculated through the application of Mann-Whitney and a statistically significant difference (p < 0005) was observed. To verify the quantity of calcium removed from sound tissue, the median of calcium in group A (0.08% Ca) was compared with that of the gold standard (0.04% Ca), which showed a close correlation of values between them. RESULTS: Indicate that the amount of calcium removed with Papacarie affects only the carious component of teeth. This goes in accordance with the principles of cavity preparation and follows the current philosophy of preventive dentistry. PMID- 20578661 TI - Efficacy of 10% Povidone Iodine in children affected with early childhood caries: an in vivo study. AB - For prevention of dental caries, S. mutans numbers must be reduced and prevented from returning to the original level. An antibacterial agent that is effective and also acceptable to young children can help to establish a favorable oral environment and halt the caries process. PURPOSE: This study was conducted to evaluate the efficacy of topical antimicrobial (10% Povidone- Iodine) on S. mutans counts in children with Early Childhood Caries after full mouth rehabilitation. Also its effects on the clinical outcomes in terms of incidence of new caries and secondary caries were evaluated. METHOD: Full mouth rehabilitation was done in 30 children (mean age 4.2 years) suffering from Severe Early Childhood Caries (SECC). Stimulated saliva samples were collected to determine the post operative baseline S. mutans counts. Thereafter the subjects were randomly divided into two groups. The experimental group received 10% Povidone Iodine at 3 months interval for a period of 12 months while the control group received placebo (deionized water) at similar intervals. Change in the S.mutans count at 6 and 12 month intervals were compared to the baseline post operative mutans score. Results revealed that application of 10% Povidone Iodine caused a significant reduction in the rise of Streptococcus mutans levels from the baseline postoperative score after 12 months of treatment thus decreasing the oral load of the organisms. Reduction in counts; in turn decreased the relapse of caries in these children. CONCLUSION: Thus oral rehabilitation coupled with regular application of 10% Povidone Iodine application can be a good alternative to control dental caries in children affected with Early Childhood Caries (ECC). PMID- 20578662 TI - Cariogenicity and acidogenicity of human milk, plain and sweetened bovine milk: an in vitro study. AB - The objective of the present study was to determine the acidogenicity and cariogenicity of human breast milk and plain and sweetened packaged bovine milk. STUDY DESIGN: First all milk specimens were inoculated with a cariogenic strain of Streptococcus mutans (SM). The culture pH and number of colony forming units (cfus) was assessed. Second, the buffer capacity of all milk specimens was evaluated by mixing with acid. Finally, enamel windows were created on extracted primary maxillary incisors and colonized with SM. Enamel demineralization and caries progression were assessed visually, histologically, and radiographically at the end of twelve weeks. RESULTS: Plain and sweetened packaged bovine milk (BM) supported greater bacterial growth and caused more fermentation than human breast milk (HBM). The buffer capacity values for plain and sweetened bovine milk were highest; HBM, however had poor buffering capacity. The progression of the carious lesions into the dentin was most severe for the sweetened bovine milk. CONCLUSIONS: HBM and plain bovine milk are relatively cariogenic in an in vitro caries model in the absence of saliva. However, supplementation with sugar exponentially enhances the cariogenic potential of the natural milk. PMID- 20578663 TI - Estimation of salivary cortisol in children with rampant caries. AB - Dental profession is largely challenged with rampant caries and probable predisposing factors for the same have been evaluated for ages. There is considerable evidence that emotional disturbances may be a causative factor in some cases of rampant caries. Thus the objective of the present study was to estimate the levels of salivary cortisol in children with active rampant caries before and after caries control using electrochemiluminescence assay. A total of 60 children between the age group of 5 to 10 years of both sexes were selected for the study. A questionnaire was also included to evaluate predisposing factors for caries. The results showed that there was an increase in salivary cortisol levels in children with rampant caries, the level decreased gradually when observed for a period of three months following dental treatment which was statistically significant. PMID- 20578664 TI - Myofibroma of the gingiva: report of a case. AB - Myofibroma is a benign mesenchymal neoplasm composed of myofibroblasts which has been described with different synonyms since the first report in 1951. It occurs most commonly as a solitary lesion of soft tissue, skin, or bone in infancy. The prognosis of oral myofibromas is excellent, and surgical excision is curative. Recurrence is rare. Awareness and recognition of this benign tumor is important to establish the correct diagnosis and avoid morbidity of unnecessary aggressive therapy. This report describes a myofibroma of the gingiva in a 14 year old girl and is reported together with the conventional histologic, and immunohistochemical findings. The tumor showed rapid increase in size and clinical features suggestive of malignancy. However on histopathologic evaluation it was diagnosed as a benign neoplasm, and this diagnosis was supported by immunohistochemical markers. The spindle cells were immunopositive for smooth muscle actin, and vimentin but were negative for desmin and S-100 protein. The patient was treated with surgical excision, and is followed-up for 33 months without any signs of recurrence. PMID- 20578665 TI - Primary oral myiasis due to Chrysomya bezziana treated with Ivermectin. A case report. AB - Primary oral myiasis due to Chrysomya bezziana is a rare condition caused by invasion of tissues by larvae of the flies. A case of Oral myiasis is presented in a 12 year old boy with neuro-degenerative disease with seizures. Intra orally, a soft tissue pocket in the left buccal mucosa and a pocket under the palatal mucosa was seen containing maggots. Extra orally indurated erythematous swelling was present near the commissure of the mouth. Predisposing factors identified in the present case were mouth breathing, incompetent lips, low socioeconomic condition, malnutrition, and inability of the child to perform daily activities due to his neurodegenerative disease. Treatment consisted of manual removal of maggots following irrigation and application of turpentine oil along with a single dose Ivermectin 3 mg that was given systemically. Complete healing of the lesion was observed within 10 days without any recurrence for a follow up period of 1 year Medical personnel taking care of old / debilitated / unconscious patients need to bear in mind the possibility of Chrysomya bezziana infestation in them. PMID- 20578666 TI - Congenital ranula. AB - This article presents 3 cases of infants with congenital ranula, a rare salivary gland pathology. Pathophysiology is discussed, differential diagnosis, and different treatment choices are explained. PMID- 20578667 TI - Presurgical nasoalveolar molding assisted primary reconstruction in complete unilateral cleft lip palate infants. AB - BACKGROUND: Various methods have been described for the primary surgical reconstruction of the unilateral cleft lip and palate deformity (UCLP) in infants. There have been several attempts at restoring the normal anatomy of the nose at the time of lip repair in the affected individuals with varying degrees of success. Presurgical nasoalveolar molding (PNAM) is a presurgical infant orthopedic procedure that attempts to target the nasal deformity leading to a more esthetic surgical repair. OBJECTIVE: At our center we aimed to use PNAM to help in providing the surgical team with a better foundation for an easier and more esthetic single stage repair at the level of nose in addition to the lip and alveolus. METHOD: The infant nasal cartilages are amenable to correction in the first few weeks of life when they retain their plasticity. Three infants with complete unilateral cleft lip palate (CUCLP) were operated upon after a course of PNAM. No nasal stents were use after repair to retain the results. RESULTS: PNAM reduced the extent of the cleft deformity and improved the anatomic relationship between the affected structures. Postoperative recovery was uneventful. Subjective evaluation immediate post surgery and at the time of palate repair reveals adequate nasolabial esthetics. Long-term results of PNAM assisted repair are to be ascertained. CONCLUSIONS: The use of PNAM enables in reducing the severity of the deformity the surgical team has to tackle thereby enabling in a better and esthetic primary repair. PMID- 20578668 TI - Oral manifestations in pediatric patients receiving chemotherapy for acute lymphoblastic leukemia. AB - The purpose of this study was to determine the prevalence of oral manifestations in pediatric patients with acute lymphoblastic leukemia (ALL) receiving chemotherapy, and to evaluate the significance of independent risk factors (oral health, gender, age, time and type of treatment, and phase of chemotherapy). A cross-sectional study was made in 49 children with ALL between 2 and 14 years of age. To describe oral manifestations, a clinical diagnosis was made and the following criteria were applied: the OHI-S index to describe oral health and the IMPA index to describe periodontal conditions and to differentiate gingivitis from periodontitis. The prevalence of oral manifestations was: gingivitis, 91.84%; caries, 81.63%; mucositis, 38.77%; periodontitis, 16.32%; cheilitis, 18.36%; recurrent herpes, 12.24%; and primary herpetic gingivostomatitis, 2.04%. Other oral manifestations were: dry lips, mucosal pallor, mucosal petechiae, ecchymoses, and induced ulcers. The prevalence of oral candidiasis was 6.12%. It was observed that high risk ALL and poor oral hygiene were important risk factors for the development of candidiasis and gingivitis. The type of leukemia, gender and phase of chemotherapy were apparently associated with the presence of candidiasis, gingivitis, and periodontitis, and they could be considered risk factors for the development of oral manifestations. PMID- 20578669 TI - Finite element method--an effective research tool for dentistry. AB - Stress analysis of dental structures has been a topic of interest in recent years with the objective of determination of stresses in the tooth and it's supporting structures and improvement of the mechanical strength of these structures. The purpose of this article is to give an insight of the finite element analysis which has totally overtaken other experimental analysis due to its ability to model even the most complex of geometries with is immensely flexible and adaptable nature. Finite Element Analysis (FEA) is a computer-based numerical technique for calculating the strength and behavior of structures. It can be used to analyze either small or large-scale deflection under loading or applied displacement. However it is extremely expensive and can be used only with the help of an expert engineer who has mastered this technique. Still this methodology of stress analysis has become extremely popular in dentistry as various properties of dental tissues and materials can be just fed into it and with the ease and accuracy the analysis is done is just remarkable. PMID- 20578670 TI - Ultrasound anatomy of normal nails unit with 18 mhz linear transducer. AB - Interest is growing in non-invasive diagnostic methods for nails in dermatological pathology. Currently, nail disease diagnosis is based mostly on clinical evaluation; instrumental examination, traditionally, has been performed by magnetic resonance. Ultrasound (US) can be proposed as an easier and more available method for the study of the nail apparatus. In this study, the nail unit normal ultrasound anatomy was investigated to obtain data on adult normal parameters. On 35 healthy volunteers (20 women and 15 men--average age of 27 years) we performed an ultrasonographic study on the nail plate (dorsal and ventral), nail matrix and nail bed of all fingers of the hands using a 18 MHz linear transducer with Esaote Mylab 50. A thick gel layer allowed for appropriate transmission of ultrasound without any additional device. Macroscopic nail features were studied by clinical examination and photographic analysis. The following ultrasound parameters were investigated: nail thickness; nail bed thickness; matrix lenght; matrix-bone distance. Blood flow was studied with the use of colour and power colour Doppler. The nail apparatus echographic anatomy consists in: (a) nail plate, represented by two hyperechoic bands (dorsal and ventral) with an hypoechoic or anechoic space between them; (b) nail bed, represented by an area of dys-homogeneous hypo-echogeneity; (c) nail matrix, represented by a markedly hypoechoic area corresponding to the region under the nail sulcus; (d) ligaments, sometimes well detectable and formed by a specialized connective tissue; and (e) vessels, well evaluable through doppler examination. PMID- 20578671 TI - A rare variation of the axillary artery combined contralaterally with an unusual high origin of a superficial ulnar artery: description, review of the literature and embryological analysis. AB - During anatomical dissection of a female Caucasian cadaver in our department we observed a combination of two rare arterial patterns of the upper limb bilaterally; a superficial ulnar artery of high origin in the right upper limb and some rare variations of the left axillary artery: Right arm: The superficial ulnar artery originated from the second part of the axillary artery, before the origin of the subscapular artery. It proceeded superficially in the forearm. The axillary artery continued normally in the arm as brachial artery, and finally divided into the radial and the common interosseous artery. The normal ulnar artery was absent. The presence of the superficial ulnar artery is a rare variation given that its total incidence ranges from 0.67% to 9.38%, with only 0.17% to 2% originating from the axillary artery. Left arm: The second part of the axillary artery gave rise to a first common trunk (named A), lying between the two roots of the median nerve, which divided in two new common trunks (B and C). One of these gave origin to the subscapular and the posterior circumflex humeral artery while the other gave rise to the anterior circumflex humeral artery, two muscle twigs and then continued as profunda brachii artery. The incidence of anatomic variations of the major arteries of the upper extremities ranges from 11% to 24%. Nevertheless a pattern with three common trunks comprising the origin of the profunda brachii has not yet been cited in the literature. PMID- 20578672 TI - Experimental study to localize the neurons projecting to the lamb retractor penis muscle. AB - Aim of the present study was to locate the neurons projecting to the lamb retractor penis muscle, a smooth muscle associated to the penis. The retrograde neuronal tracer Fast Blue was injected into the bulbopenile portion of the left retractor penis muscle. Labelled cells were found bilaterally in the S2-S4 spinal ganglia, from the last two lumbar (L5-L6 or L6-L7) to S4 sympathetic trunk ganglia and in the hypogastric and pelvic plexuses. Fast blue-positive (FB+) neurons were also found in the intermediate gray substance in the S1-S4 segments of the spinal cord. Our research enables us to describe the organization of the innervation of the lamb retractor penis muscle, highlighting the site of the primary afferent, postganglionic efferent and presumably preganglionic parasympathetic neurons projecting to the muscle. PMID- 20578674 TI - Safety issues in didactic anatomical dissection in regions of high HIV prevalence. AB - Ruggiero et al. (2009) have recently reviewed the importance of dissection in the training of physicians, the role played by students' fears of infection, and the evidence that those sometimes extreme fears are unwarranted even respecting HIV and AIDS, whose dangers continue to be featured prominently in popular media as though everyone were at constant risk. It is not especially surprising that the risk of accidental infection by HIV is negligibly low in random dissections in Italy where, as in Europe generally, the prevalence of HIV is only a fraction of a percent. The question arises, however, what the risk might be in regions where the prevalence of HIV is considerably higher. South Africa is an obvious candidate for investigating this issue since the prevalence of HIV there is among the highest reported by UNAIDS and other official bodies. Furthermore, its recordkeeping system is more reliable than that of most other countries in sub Saharan Africa, the global region that is universally regarded as the epicenter of the HIV/AIDS epidemic. In addition, South Africa has a globally recognized reputation in the teaching of human anatomy. Perhaps surprisingly, the risks in South Africa also seem to be much less than might be anticipated on the basis of the conventional wisdom. One reason for this counter-intuitive conclusion is that estimates of HIV prevalence and of AIDS deaths issued by international bodies are significantly overblown, with some estimates being 20 times or more greater than locally recorded numbers. A second basis for the unexpected conclusion is that the possibility of false-positive HIV tests has been ignored despite the considerable range of evidence that false-positives can be a significant part, perhaps even a major part, of positive tests in certain groups or certain regions, saliently among people of African ancestry. PMID- 20578673 TI - Morphometric analysis of the skull of the Sahel goat breed: basic and clinical anatomy. AB - The work reports morphometric analysis of the skulls of the Sahel breed of goat. The calculated metric data (mean +/- SD) included the condylobasal length, 16.94 +/- 1.39 cm, while the orbital circumference was 11.30 +/- 0.48 cm. The foramen magnum height and width were 1.82 +/- 0.11 cm and 1.85 +/- 0.15 cm respectively while the foramen magnum index was 89.81 +/- 8.71. Animals above one year of age had significantly higher values for orbital length including horizontal and vertical diameters, overall skull length, basal length, and neurocranium height than animals aged one year and below. The cornual process length, maximum orbital circumference and horizontal diameter obtained in this study were higher than those reported for other Nigerian goat breeds in the literature. The data for the distances from the facial tuberosity to the infraorbital canal, from the mental foramen to the lateral extent of the alveolar root of the lower incisor, as well as from the mandibular foramen to the base of the mandible and that from the mental foramen to the caudal border of the mandible, which are important clinically in the estimation of craniofacial measurements that will aid regional anaesthesia, were however similar to those reported earlier for the Red Sokoto and West African Dwarf breeds implying that a uniform craniometric estimation for associated regional nerve blocks can be attempted for these goat breeds. PMID- 20578675 TI - Immunohistochemical analysis of the COX-2 marker in acute pulmonary injury in rats. AB - Acute inflammatory response is one of the main defensive mechanisms of the lungs. This work tried to assess this response through an immunohistochemical analysis of rat lungs mechanically injured by open manipulation, analyzing the COX-2 inflammatory marker, in addition to performing a microscopic histological analysis using the hematoxylin and eosin stain. The correlation between this response and the degree of manipulation over different lengths of time and degrees of injury was also investigated. Sixteen rats were divided into four groups and subjected to anterior thoracotomy. The upper lobe of the right lung was compressed using a plastic Bulldog clamp for different time length according to group (5 minutes, 2 minutes, and three 10-second compressions with 10 second intervals). The control group was subjected to thoracotomy but their lungs were not compressed. The injured lobes were analyzed histologically and subjected to immunohistochemistry and the results were compared. There were no differences in the immunohistochemical patterns between the control and injured rats, but the histological patterns between them differed. In conclusion, the histological analysis shows that the degree of injury caused by clamping the pulmonary parenchyma increases as the time length of compression increases but this inflammatory response is not paralleled by modifications of the COX-2 marker at immunohistochemistry. PMID- 20578677 TI - Total synthesis of cryptoacetalide. AB - We are reporting the first total synthesis of the tetracyclic terpene natural product cryptoacetalide. Key steps of the synthesis are a microwave-mediated [2+2+2] cyclo-trimerization reaction to construct the central benzene ring, and a light-mediated radical cyclization to assemble the spiro-ketal moiety. PMID- 20578676 TI - Microfibrils: a cornerstone of extracellular matrix and a key to understand Marfan syndrome. AB - The extracellular matrix is made of collagen, reticular, elastic and oxytalan fibers, amorphous ground substance and adhesive proteins playing a structural role, such as fibronectin; the basement membrane is a specialized matrix compartment which adheres to non-connective tissues and is continuous with the remaining matrix thanks to reticular fibers, anchoring fibrils, collagen VI filaments and oxytalan fibers. Microfibrils are constituents of elastic and oxytalan fibers that confer mechanical stability and limited elasticity to tissues, contribute to growth factor regulation, and play a role in tissue development and homeostasis. The microfibril core is made of the glycoprotein fibrillin, of which three types are known. Other concurring molecules are microfibril associated proteins (MFAPs) and microfibril associated glycoproteins (MAGPs); they, and other peripheral molecules, contribute to link microfibrils to elastin, to other extracellular matrix components and to cells. Fibrillinopathies are genetic disorders due to mutations in fibrillin genes (FBN). The most frequent is Marfan syndrome, caused by mutations in FBN-1 and involving primarily the cardiovascular, skeletal, ocular and central nervous systems. Several mutations have been identified, which lead to alteration or reduction in the secretion or assembly of fibrillin molecules and to increased microfibril proteolysis. Marfan related disorders are associated with alterations of TGF-beta signaling that interfere with extracellular matrix formation. Understanding the pathogenesis of Marfan and related syndromes requires advances in the physiology of the extracellular matrix and in turn can cast light on the roles of microfibrils and of extracellular matrix in general in organ formation and function. PMID- 20578678 TI - Antimicrobial particles from cationic lipid and polyelectrolytes. AB - Hybrid nanoparticles from cationic lipid and polymers were prepared and characterized regarding physical properties and antimicrobial activity. Carboxymethylcellulose (CMC) and polydiallyldimethylammonium chloride (PDDA) were sequentially added to cationic bilayer fragments (BF) prepared from ultrasonic dispersion in water of the synthetic and cationic lipid dioctadecyldimethylammonium bromide (DODAB). Particles thus obtained were characterized by dynamic light-scattering for determination of z-average diameter (Dz) and zeta-potential (zeta). Antimicrobial activity of the DODAB BF/CMC/PDDA particles against Pseudomonas aeruginosa or Staphylococcus aureus was determined by plating and CFU counting over a range of particle compositions. DODAB BF/CMC/PDDA particles exhibited sizes and zeta-potentials strictly dependent on DODAB, CMC, and PDDA concentrations. At 0.1 mM DODAB, 0.1 mg/mL CMC, and 0.1 mg/mL PDDA, small cationic particles with Dz = 100 nm and zeta = 30 mV were obtained. At 0.5 mM DODAB, 0.5 mg/mL CMC and 0.5 mg/mL PDDA, large cationic particles with Dz = 470 nm and zeta = 50 mV were obtained. Both particulates were highly reproducible regarding physical properties and yielded 0% of P. aeruginosa viability (10(7) CFU/mL) at 1 or 2 microg/mL PDDA dissolved in solution or in form of particles, respectively. 99% of S. aureus cells died at 10 microg/mL PDDA alone or in small or large DODAB BF/CMC/PDDA particles. The antimicrobial effect was dependent on the amount of positive charge on particles and independent of particle size. A high microbicide potency for PDDA over a range of nanomolar concentrations was disclosed. P. aeruginosa was more sensitive to all cationic assemblies than S. aureus. PMID- 20578679 TI - Palladium-catalyzed decarboxylative coupling of alkynyl carboxylic acids with benzyl halides or aryl halides. AB - The synthesis of internal benzyl alkynes and 1,2-diarylalkynes has been developed via palladium-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids with benzyl chlorides or aryl halides. In the presence of Pd(OAc)(2) and Xphos (L3), alkynyl carboxylic acids smoothly underwent the reaction with various benzyl halides, providing the corresponding benzyl alkynes in moderate to good yields. It is noteworthy that the optimal conditions are compatible with a wide range of aryl halides including less active aryl chlorides. PMID- 20578681 TI - Perchloric acid catalyzed homogeneous and heterogeneous addition of beta dicarbonyl compounds to alcohols and alkenes and investigation of the mechanism. AB - The direct addition of various beta-dicarbonyl compounds to a series of secondary alcohols and alkenes has been achieved using 1 mol % perchloric acid (HClO(4)) as the catalyst. The HClO(4)-catalyzed reactions could be conveniently conducted in commercial solvent and gave moderate to excellent yields. Moreover, the silica gel-supported HClO(4) could also catalyze the heterogeneous addition for a series of substrates with similar or even higher yields in comparison with the homogeneous ones. The supported catalyst could be readily recovered and reused for four runs. Furthermore, the mechanism of the HClO(4)-catalyzed addition of the beta-diketone to alcohol was investigated, and an S(N)1 mechanism was proved unambiguously for the first time through a series of experiments. The discrimination of catalytic abilities among different Bronsted acids was also rationalized by DFT calculations. PMID- 20578680 TI - Evaluation of the identification power of RPLC analyses in the screening for drug compounds. AB - The identification of drugs of abuse is an important issue in forensic science. The main goal is to trace and identify as many drugs as possible in the shortest possible time preferably with a simple analysis method. One possibility is to screen samples using a Liquid Chromatography-Diode Array Detection (LC-DAD) system. However, when simultaneously performing another analysis on a chromatographic column exhibiting selectivity differences from the first one, that is, orthogonal or dissimilar columns, a greater number of drugs can be possibly identified without investing a lot of extra time or money. The primary difficulty is then selecting the most appropriate columns. In this paper, it is demonstrated that selecting the most dissimilar columns based on measures such as correlation or Snyder's F(s) value is not optimal, because these measures do not take into account the identification power of the individual systems. This implies that a large number of drugs may not necessarily be identified on the systems selected using these criteria. Therefore, three other measures are tested to evaluate the identification power obtained by parallel screening on two columns or by comprehensive two-dimensional LC (LC x LC). The simplest approach is counting the number of compounds separable with a difference in retention time greater than a predefined critical value. However, this measure does not reflect the coelution pattern of the unidentified drugs nor the separation degree of all compounds. The second tested measure, information, enables differentiation between systems identifying the same number of compounds but resulting in a different coelution pattern. Multivariate selectivity, the third tested parameter, takes into account the degree of separation of all compounds and has the advantage that it reflects the gain in identification power achieved by introducing DAD data. All three proposed measures also enable evaluation of whether the corresponding LC x LC method will result in a greater identification power. PMID- 20578682 TI - Formation of a 1,8-octanedithiol self-assembled monolayer on Au(111) prepared in a lyotropic liquid-crystalline medium. AB - A characterization of the 1,8-octanedithiol (ODT) self-assembled monolayer (SAM) formed from a Triton X-100 lyotropic medium has been conducted by electrochemical techniques. It is found that an ODT layer of standing-up molecules is obtained at short modification time without removing oxygen from the medium. The electrochemical study shows that the ODT layer formed after 15 min of modification time has similar electron-transfer blocking properties to the layers formed from organic solvents at much longer modification times. On the basis of XPS data, it is demonstrated that the inability to bind gold nanoparticles (AuNPs) is due to the presence of extra ODT molecules either interdigited or on top of the layer. Treatment consisting of an acid washing step following the formation of the ODT-Au(111) SAM produces a layer that is able to attach AuNPs as demonstrated by electrochemical techniques and atomic force microscopy (AFM) images. PMID- 20578683 TI - Flexible organic transistor memory devices. AB - The flexible nonvolatile organic memory devices were developed on the plastic substrates based on the organic thin-film transistors embedding self-assembled gold nanoparticles (Au(NP)). The organic memory devices exhibited good programmable memory characteristics with respect to the program/erase operations, resulting in controllable and reliable threshold voltage shifts. Additionally, the endurance, data retention, and bending cyclic measurements confirmed that the flexible memory devices exhibited good electrical reliability as well as mechanical stability. The memory devices were composed of the solution-processed organic dielectric layers/metallic nanoparticles and the low-temperature processed organic transistors. Therefore, this approach could potentially be applied to advanced flexible/plastic electronic devices as well as integrated organic device circuits. PMID- 20578684 TI - New type of BiPO(4) oxy-acid salt photocatalyst with high photocatalytic activity on degradation of dye. AB - A high photocatalytic BiPO(4) with a novel nonmetal oxy acid structure is synthesized by a hydrothermal method. BiPO(4) photocatalyst has an optical indirect band gap of 3.85 eV. In a comparison of BiPO(4) with that of TiO(2) (P25, Degussa), it is found that the photocatalytic activity of BiPO(4) is twice that of TiO(2) (P25, Degussa) for the degradation of methylene blue (MB) dye, while the BET surface of BiPO(4) is just one tenth of that of P25. Both the high position of the valence band and the high separation efficiency of electron-hole pairs result in the high photocatalytic activity. The inductive effect of PO(4)(3 ) helps the e(-)/h(+) separation, which plays an important role in its excellent photocatalytic activity. It may extend to the synthesis of other inorganic nonmetal salts of oxy photocatalysts with suitable band gap and high activity for the environmental purification of organic pollutants in aqueous solution. PMID- 20578685 TI - Reactive nitrogen species in acetaminophen-induced mitochondrial damage and toxicity in mouse hepatocytes. AB - Acetaminophen (APAP) toxicity in primary mouse hepatocytes occurs in two phases. The initial phase (0-2 h) occurs with metabolism to N-acetyl-p-benzoquinoneimine which depletes glutathione, and covalently binds to proteins, but little toxicity is observed. Subsequent washing of hepatocytes to remove APAP and reincubating in media alone (2-5 h) results in toxicity. We previously reported that the reincubation phase occurs with mitochondrial permeability transition (MPT) and increased oxidative stress (dichlorodihydrofluorescein fluorescence) (DCFH(2)). Since DCFH(2) may be oxidized by multiple oxidative mechanisms, we investigated the role of reactive nitrogen species (RNS) leading to 3-nitrotyrosine in proteins by ELISA and by immunoblots. Incubation of APAP with hepatocytes for 2 h did not result in toxicity or protein nitration; however, washing hepatocytes and reincubating in media alone (2-5 h) resulted in protein nitration which correlated with toxicity. Inclusion of the MPT inhibitor, cyclosporine A, in the reincubation media eliminated toxicity and protein nitration. The general nitric oxide synthase (NOS) inhibitor L-NMMA and the neuronal NOS (NOS1) inhibitor, 7 nitroindazole, added in the reincubation media decreased toxicity and protein nitration; however, neither the inducible NOS (NOS2) inhibitors L-NIL (N6-(1 iminoethyl)-L-lysine) nor SAIT (S-(2-aminoethyl)isothiourea) decreased protein nitration or toxicity. The RNS scavengers, N-acetylcysteine, and high concentrations of APAP, added in the reincubation phase decreased toxicity and protein nitration. 7-Nitroindazole and cyclosporine A inhibited the APAP-induced loss of mitochondrial membrane potential when added in the reincubation phase. The data indicate a role for RNS in APAP induced toxicity. PMID- 20578687 TI - Enantioselective Wacker-type cyclization of 2-alkenyl-1,3-diketones promoted by Pd-SPRIX catalyst. AB - An enantioselective intramolecular Wacker-type cyclization of 2-alkenyl-1,3 diketones catalyzed by a Pd(II)-SPRIX complex was developed. The reaction proceeded in a 6-endo-trig mode to give the desired chromene derivatives with moderate to good enantioselectivity. Isomerization of C-C double bonds via a pi allyl Pd intermediate was involved as the key step. PMID- 20578686 TI - UV-induced bond modifications in thymine and thymine dideoxynucleotide: structural elucidation of isomers by differential mobility mass spectrometry. AB - Differential mobility spectrometry has been applied to reveal the occurrence of isomerization of thymine nucleobase and of thymine dideoxynucleotide d(5'-TT-3') due to bond redisposition induced by UV irradiation at 254 nm of frozen aqueous solutions of these molecules. Collision-induced dissociation (CID) spectra of electrosprayed photoproducts of the thymine solution suggest the presence of two isomers (the so-called cyclobutane and 6,4-photoproducts) in addition to the proton-bound thymine dimer, and these were separated using differential mobility spectrometry/mass spectrometry (DMS/MS) techniques with water as the modifier. Similar experiments with d(5'-TT-3') revealed the formation of a new isomer of deprotonated thymine dideoxynucleotide upon UV irradiation that was easily distinguished using DMS/MS with isopropanol as the modifier. The results reinforce the usefulness of DMS/MS in isomer separation. PMID- 20578688 TI - CaCu3Pt4O12: the first perovskite with the B site fully occupied by Pt(4+). AB - A novel A-site ordered perovskite CaCu(3)Pt(4)O(12) was synthesized under high pressure and high temperature of 12 GPa and 1250 degrees C. CaCu(3)Pt(4)O(12) is the first perovskite in which the B site is fully occupied by Pt(4+). The crystal structure refinement based on the synchrotron powder X-ray diffraction data shows that CaCu(3)Pt(4)O(12) crystallizes in the space group Im3 (cubic) with a lattice constant of a = 7.48946(10) A. The magnetic susceptibility data show the antiferromagnetic transition at T(N) = 40 K, which is attributed to the magnetic ordering of Cu(2+) spins with S = 1/2. PMID- 20578689 TI - Molecular dynamics of an embedded-charge model of lysozyme aqueous solutions. AB - The onset of liquid-vapor separation in an interaction site model of a lysozyme aqueous solution is investigated by means of molecular dynamics (MD). Calculations are performed for a soft-core version of a potential early introduced by Carlsson et al. (J. Phys. Chem. B 2001, 105, 9040; 2001, 105, 12189.) whose liquid-vapor coexistence was studied by Rosch and Errington (J. Phys. Chem. B 2007, 111, 12591.); our modified model preserves the tailoring onto the experimental lysozyme solution properties embodied by those descriptions. We first show that the structural results obtained by Carlsson et al. at ambient conditions are quite well reproduced by our approach. Then, we cool the system along an isochoric path by monitoring the structural and dynamical properties at various temperatures. We thus show that a fluid-fluid separation takes place at a temperature 15% below the presumed binodal; in particular, we observe that density inhomogeneities develop rather early in the MD run and evolve over tens of nanoseconds into two dense aggregates that eventually merge, after approximately 100 ns more, into a single liquid phase separated from a vapor region by a well-defined planar interface. The densities of the two coexisting fluids are compatible with previous determinations of the binodal line. The connections of this work to the overall scenario of phase stability investigations in protein solutions, as well as possible developments based on the use of more refined models, are discussed. PMID- 20578690 TI - Relating energy level alignment and amine-linked single molecule junction conductance. AB - Using photoemission spectroscopy, we determine the relationship between electronic energy level alignment at a metal-molecule interface and single molecule junction transport data. We measure the position of the highest occupied molecular orbital (HOMO) relative to the Au metal Fermi level for three 1,4 benzenediamine derivatives on Au(111) and Au(110) with ultraviolet and resonant X ray photoemission spectroscopy. We compare these results to scanning tunnelling microscope-based break-junction measurements of single molecule conductance and to first-principles calculations. We find that the energy difference between the HOMO and Fermi level for the three molecules adsorbed on Au(111) correlate well with changes in conductance and agree well with quasiparticle energies computed from first-principles calculations incorporating self-energy corrections. On the Au(110) that presents Au atoms with lower-coordination, critical in break junction conductance measurements, we see that the HOMO level shifts further from the Fermi level. These results provide the first direct comparison of spectroscopic energy level alignment measurements with single molecule junction transport data. PMID- 20578691 TI - Fermentanomics: monitoring mammalian cell cultures with NMR spectroscopy. AB - As the number of therapeutic proteins produced by mammalian cell cultures in the pharmaceutical industry continues to increase, the need to improve productivity and ensure consistent product quality during process development activities becomes more significant. Rational medium design is known to improve cell culture performance, but an understanding of nutrient consumption and metabolite accumulation within the medium is required. To this end, we have developed a technique for using 1D (1)H NMR to quantitate nonprotein feed components and metabolites in mammalian cell cultures. We refer to the methodology as "Fermentanomics" to differentiate it from standard metabolomics. The method was found to generate spectra with excellent water suppression, signal-to-noise, and resolution. More importantly, nutrient consumption and metabolite accumulation was readily observed. In total, 50 media components have been identified and quantitated. The application of Fermentanomics to the optimization of a proprietary CHO basal medium yielded valuable insight regarding the nutrient levels needed to maintain productivity. While the focus here is on the extracellular milieu of CHO cell cultures, this methodology is generally applicable to quantitating intracellular concentrations and can be extended to other mammalian cell lines, as well as platforms such as yeasts, fungi, and Escherichia coli. PMID- 20578692 TI - In vitro formation of amyloid from alpha-synuclein is dominated by reactions at hydrophobic interfaces. AB - Most in vitro investigations of alpha-Synuclein (alphaSyn) aggregation and amyloidogenesis use agitation in the presence of air and/or Teflon to accelerate kinetics. The effect of the agitation is implicitly or explicitly attributed to mass transfer or fibril fragmentation. This paper evaluates these hypotheses by agitating alphaSyn under typical amyloidogenic conditions with controlled numbers of balls made of polytetrafluoroethylene (PTFE), polymethylmethacrylate (PMMA), and borosilicate glass with no headspace. Amyloid was assayed using thioflavin T fluorescence and atomic force microscopy. The observed kinetics were proportional to the PTFE surface area; the effects of PMMA and glass balls were negligible by comparison. No amyloid was observed to form in the absence of mixing balls. Agitation with only air also showed accelerated kinetics but different aggregate morphology. The results indicate that the mechanism active in agitation experiments is dominated by reactions at the hydrophobic-water interface. Of the mass transfer, fragmentation, and hydrophobic interface hypotheses, only the last is capable of explaining the data. Condition and sequence determinants of amyloidogenic propensity that have thus far been reported must be reinterpreted as being reflective of partitioning to hydrophobic-water interfaces. Comparable hydrophobic interfaces are not found in vivo. PMID- 20578693 TI - Functional reconstitution of an ABC transporter in nanodiscs for use in electron paramagnetic resonance spectroscopy. AB - Electron paramagnetic resonance (EPR) spectroscopy is a powerful biophysical technique for study of the structural dynamics of membrane proteins. Many of these proteins interact with ligands or proteins on one or both sides of the membrane. Membrane proteins are typically reconstituted in proteoliposomes to observe their function in a physiologically relevant environment. However, membrane proteins can insert into liposomes in two different orientations, and surfaces facing the lumen of the vesicle can be inaccessible to ligands. This heterogeneity can lead to subpopulations that do not respond to ligand binding, complicating EPR spectral analysis, particularly for distance measurements. Using the well-characterized maltose transporter, an ATP binding cassette (ABC) transporter that interacts with ligands on both sides of the membrane, we provide evidence that reconstitution into nanodiscs, which are soluble disk-shaped phospholipid bilayers, is an ideal solution to these problems. We describe the functional reconstitution of the maltose transporter into nanodiscs and demonstrate that this system is ideally suited to study conformational changes and intramolecular distances by EPR. PMID- 20578695 TI - Kinetic isolation and characterization of the radical rearrangement step in coenzyme B12-dependent ethanolamine ammonia-lyase. AB - The transient decay reaction kinetics of the 1,1,2,2-(2)H(4)-aminoethanol generated Co(II)-substrate radical pair catalytic intermediate in ethanolamine ammonia-lyase (EAL) from Salmonella typhimurium have been measured by using time resolved, full-spectrum X-band continuous-wave electron paramagnetic resonance (EPR) spectroscopy in frozen aqueous solution over the temperature range of 190 207 K. The decay reaction involves sequential passage through the rearrangement step [substrate radical --> product radical] and the step [product radical --> diamagnetic product] that involves hydrogen atom transfer (HT) from carbon C5' of the adenosine moiety of the cofactor to the product radical C2 center. As found for the (1)H-substrate radical [Zhu, C.; Warncke, K. Biophys. J. 2008, 95, 5890], the decay kinetics for the (2)H-substrate radical over 190-207 K represent two noninteracting populations (fast decay population: normalized amplitude = 0.44 +/ 0.07; observed rate constant, k(obs,f) = 5.3 x 10(-5)-1.1 x 10(-3) s(-1); slow decay population: k(obs,s) = 6.1 x 10(-6)-2.9 x 10(-4) s(-1)). The (1)H/(2)H isotope effects (IE) for the fast and slow decay reactions are 1.4 +/- 0.2 and 0.79 +/- 0.11, respectively. The IE on the fast phase is uniform over the temperature interval, and the value is consistent with an alpha-secondary hydrogen kinetic IE, which arises from changes in the force constants of the C-H bonds in the substrate radical structure, upon passing from the substrate radical state to the rearrangement transition state. Therefore, we propose that k(obs,f) represents the rate constant for the radical rearrangement and that this step is the rate-determining step in substrate radical decay. The Arrhenius activation energy for the (1)H-substrate radical rearrangement (13.5 +/- 0.4 kcal/mol) is consistent with values from quantum chemical calculations performed on simple models. The results show that the core, radical rearrangement reaction is culled from the catalytic cycle in the low-temperature system, thus establishing the system for detailed transient kinetic and spectroscopic analysis of protein structural and dynamic contributions to EAL catalysis. PMID- 20578696 TI - Control of the orientational order and nonlinear optical response of the "push pull" chromophore RuPZn via specific incorporation into densely packed monolayer ensembles of an amphiphilic 4-helix bundle peptide: second harmonic generation at high chromophore densities. AB - The macroscopic nonlinear optical response of the "push-pull" chromophore RuPZn incorporated into a single monolayer of the amphiphilic 4-helix bundle peptide (AP0) covalently attached to a solid substrate at high in-plane density has been measured. The second-order susceptibility, chi(zzz), was found to be in the range of approximately 15 x 10(-9) esu, consistent with a coherent sum of the nonlinear contributions from the individual chromophores (beta) as previously measured in isotropic solution through hyper-Rayleigh scattering as well as estimated from theoretical calculations. The microscopic hyperpolarizability of the RuPZn chromophore is preserved upon incorporation into the peptide monolayer, suggesting that the chromophore-chromophore interactions in the densely packed ensemble do not substantially affect the first-order molecular hyperpolarizability. The polarization angle dependence of the second harmonic signal reveals that the chromophore is vectorially oriented in the two dimensional ensemble. Analysis of the order parameter together with information obtained from grazing incidence X-ray diffraction help in determining the chromophore orientation within the AP0-RuPZn monolayer. Taking into account an average pitch angle of approximately 20 degrees characterizing the coiled-coil structure of the peptide bundle, the width of the bundle's tilt angle distribution should be sigma < or = 20 degrees, resulting in a mean value of the tilt angle 23 degrees < or = theta(0) < or = 37 degrees. PMID- 20578697 TI - Fully substituted carbon centers by diastereoselective spirocyclization: stereoselective synthesis of (+)-lepadiformine C. AB - Reductive lithiation of N-Boc alpha-amino nitriles generated alpha-amino alkyllithium reagents with unexpected selectivity. The intermediate radical prefers to align with the nitrogen lone pair, and this interaction leads to an A(1,3)-strain effect that biases the conformation of the radical. In cyclohexane rings with alpha-substituents the net effect is an inversion of configuration on reductive lithiation. In the presence of a tethered electrophile the alkyllithium cyclizes to produce a spiro compound, again with inversion of configuration. The overall result is retention of configuration in the cyclization reaction. The same overall selectivity is found with alpha-oxygen alkyllithium cyclizations, but in this case both steps proceed with retention. The difference can be explained by careful consideration of the intermediate geometries. The alpha amino spirocyclization was utilized in a concise and stereoselective synthesis of lepadiformine C. PMID- 20578698 TI - Persistently folded circular aromatic amide pentamers containing modularly tunable cation-binding cavities with high ion selectivity. AB - In this work, we illustrated a novel design strategy that allows systematically tunable interior properties (effective cavity size, steric crowdedness, and hydrophobicity) contained within a novel class of shape-persistent aromatic pentamers to take place on a scale below 3 A. Such finely tunable structural features are complimented by experimentally observable functional variations in ion-binding potential. Results of the selective, differential binding affinities of three circular pentamers for Li(+), Na(+), K(+), Rb(+), and Cs(+), substantiated by metal-containing crystal structures and computational modeling, are detailed. PMID- 20578700 TI - Global pilot study of legacy and emerging persistent organic pollutants using sorbent-impregnated polyurethane foam disk passive air samplers. AB - Sorbent-impregnated polyurethane foam (SIP) disk passive air samplers were deployed alongside polyurethane foam (PUF) disk samplers at 20 sites during the 2009 spring sampling period of the Global Atmospheric Passive Sampling (GAPS) Network. The SIP disk samplers consisted of PUF disks impregnated with finely ground XAD-4 resin. The addition of XAD-4 greatly improves the sorptive capacity of the PUF disk samplers for more volatile and polar chemicals, and allows for linear-phase sampling over several weeks for these compounds. The SIP and PUF disks were analyzed for polychlorinated biphenyls (PCBs), neutral polyfluoroalkyl compounds (PFCs), and ionic PFCs. Correlations between sampler-derived air concentrations for PCBs in the PUF and SIP disks samplers were significant (p < 0.05). The SIP disks effectively captured 4-50% more of the low molecular weight PCBs than the PUF disks samplers, and the PUF disks also had limitations for time weighted passive sampling of neutral PFCs in air. Theoretical uptake curves for PUF disks showed rapid equilibration occurring in just hours for 8:2 FTOH and in a few days for MeFOSE, while theoretical curves for SIP disks showed superior sampling profiles for the neutral PFCs. PFCs were measured on SIP disks at all sites with 8:2 FTOH being the dominant compound detected and urban centers (n = 3) having the highest total neutral PFC concentrations ranging from 51.7 to 248 pg/m(3). A positive correlation was found between the FTOHs and FOSAs/FOSEs (p < 0.001, Pearson correlation) indicating similar contamination sources. The SIP disk appears to be a promising passive air sampler for measuring both emerging and legacy POPs on a global scale. They can also be used as a complement to the PUF disk sampler for capturing broader classes of compounds, or as a replacement for PUF disks entirely, especially when longer than quarterly deployment periods are desired. PMID- 20578699 TI - Complexes of bacterial nicotinate mononucleotide adenylyltransferase with inhibitors: implication for structure-based drug design and improvement. AB - Bacterial nicotinate mononucleotide adenylyltransferase encoded by the essential gene nadD plays a central role in the synthesis of the redox cofactor NAD(+). The NadD enzyme is conserved in the majority of bacterial species and has been recognized as a novel target for developing new and potentially broad-spectrum antibacterial therapeutics. Here we report the crystal structures of Bacillus anthracis NadD in complex with three NadD inhibitors, including two analogues synthesized in the present study. These structures revealed a common binding site shared by different classes of NadD inhibitors and explored the chemical environment surrounding this site. The structural data obtained here also showed that the subtle changes in ligand structure can lead to significant changes in the binding mode, information that will be useful for future structure-based optimization and design of high affinity inhibitors. PMID- 20578702 TI - First-principles prediction on the high-pressure structures of transition metal diborides (TMB2, TM = Sc, Ti, Y, Zr). AB - We have extensively explored the high-pressure structures of transition-metal diborides (TMB(2), TM = Sc, Ti, Y, and Zr) stabilized with the AlB(2)-type structure at ambient pressure by using first-principles structural prediction. We find two novel high-pressure structures: (i) a monoclinic structure (C2/m, Z = 4) for ScB(2) and YB(2) stable above 208 and 163 GPa, respectively; and (ii) a tetragonal alpha-ThSi(2)-type phase (I4(1)/amd, Z = 4) for TiB(2) stable above 215 GPa. Our calculations show that the electron transfer from transition-metals TM to B under pressure might be the main cause for the structural phase transitions. Further phonon and hardness calculations suggest that alpha-ThSi(2) phase of TiB(2) is quenchable to ambient pressure and possesses excellent mechanical property with a Vickers hardness of 29.8 GPa. Interestingly, ZrB(2) is quite stable and persists on the ambient-pressure AlB(2)-type structure up to at least 300 GPa. We attribute the strong covalent hybridization between the transition-metal Zr and B to this ultrastability. PMID- 20578701 TI - Electrical sensor array for polymerase chain reaction-free messenger RNA expression profiling. AB - A simple and sensitive electrical sensor array for polymerase chain reaction-free (PCR-free) messenger RNA (mRNA) expression profiling is described in this work. The sensor array, consisting of vertically aligned gold microband electrode/SiO(2)/gold microband electrode sandwich structures (nanogap sensors) in orthogonal configurations, was fabricated on a 1 cm x 1 cm silicon chip. A target mRNA was first hybridized with its specific capture probes (CP) on the bottom side of the nanogap, followed by a second hybridization (annealing) of its poly(A) tail with poly(T) annealing probes (AP) on the top side of the nanogap, holding the hybridized mRNA strands vertically across the nanogap. A subsequent metallization of the hybridized mRNA strands bridged the nanogap and consequently produced a substantial change in conductance, allowing ultrasensitive detection of mRNA without any amplification. Noticeable conductance changes were observed in the presence of as little as 0.10 fM mRNA. A linear relationship between the conductance and mRNA concentration was obtained from 0.50 fM to 1.0 pM with exceptional signal intensity. As little as a 50% difference in mRNA expression was successfully detected. The sensor array also exhibited excellent mismatch discrimination due to its unique vertically aligned nanostructure and the two step hybridization. PMID- 20578703 TI - Accumulation, distribution, and speciation of arsenic in wheat grain. AB - Food can be an important source of inorganic As for human intake. Recent studies have focused on rice, while little information is available on As accumulation, distribution, and speciation in wheat, which is the second most important food grain cereal. Grain samples of 26 wheat cultivars grown in five field trials located in productive farming regions in Europe were therefore analyzed for As concentration and speciation. Grain from four trials contained low concentrations of total As (7.7 +/- 5.4 microg kg(-1)), reflecting low levels of As in the soils (1.3-11 mg kg(-1)). In contrast, at one of the trial sites the As level in the soil was greater (29 mg kg(-1)), and much higher As concentrations (69 +/- 17 microg kg(-1)) were present in the wheat grain. Milling of wheat grain into bran and white flour fraction showed the concentration of As in the bran, with a 3.8 4.7-fold higher As concentration than in the white flour. Two methods (a phosphate buffer solution and 1% HNO(3)) were used to extract As species from wholemeal, bran, and white flour of wheat, with average extraction efficiencies of 65% and 88%, respectively. Only inorganic As was found in the extracts, with no methylated As being detected. The contribution of wheat to human intake of inorganic As is small for wheat crops grown in uncontaminated soils but becomes significant for those grown in soils with elevated As. In the latter case, milling can be used to reduce the As concentration in the white flour. PMID- 20578704 TI - Mobility of polycyclic aromatic hydrocarbons in the gastrointestinal tract assessed using an in vitro digestion model with sorption rectification. AB - In a previous study, it was demonstrated that mobilization of organochlorine pesticides would be underestimated by an in vitro gastrointestinal model if the sorption of the mobilized pollutants on the digestive residue was not taken into consideration. A multiple fluid/solid ratio procedure was developed to characterize the sorption. In this study, the sorption hypothesis was further tested for polycyclic aromatic hydrocarbons (PAHs), and the sorption of the mobilized PAHs on digestive residue was directly characterized by spiking the gastrointestinal digest with several deuterated PAHs. It was demonstrated that 10 41% of the spiked deuterated PAHs were sorbed on the assimilated residue, which would remain in the solid phase after separation. It appears that the mobility of PAHs would be underestimated if only those dissolved in the fluid is measured. The total mobilized fraction of a PAH compound was defined as a sum of that dissolved in the fluid and that sorbed on the residue. The average mobilized PAH fractions in the studied soils was 70 +/- 24% which was significantly higher than 47 +/- 19% in the fluid. It was also found that the sorption of the mobilized PAHs on the digestive residue was positively correlated with both soil organic carbon (SOC) and molecular weight (MW(t)) of PAHs, and a regression model was developed so that the sorption of different PAHs on soils with different SOCs could be estimated. PMID- 20578705 TI - trans-resveratrol inhibits hyperglycemia-induced inflammation and connexin downregulation in retinal pigment epithelial cells. AB - The purpose of this study was to determine the inhibitory activity of trans resveratrol against hyperglycemia-induced inflammation and degradation of gap junction intercellular communication in retinal pigment epithelial cells. Retinal (ARPE-19) cells were incubated with 5.5 mM glucose, 5.5 mM glucose and 10 microM resveratrol, 33 mM glucose, or 33 mM glucose and 0-10 microM trans-resveratrol at 37 degrees C and 5% CO(2) for 9 days. Cell viability was determined by the crystal violet assay. The levels of low-grade inflammation biomarkers interleukin 6 and interleukin-8 (IL-6 and IL-8), angiogenic factors, and vascular endothelial growth factor (VEGF) were determined by the enzyme-linked immunosorbent assay (ELISA). Gap junction intercellular communication (GJIC) was determined by the scrape-load/dye transfer method. The expression levels of protein kinase Cbeta (PKCbeta), connexin 43 (Cx43), transforming growth factor-beta1 (TGF-beta1), and cyclooxygenase-2 (COX-2) were determined by Western blot. Incubation of retinal cells with 10 microM trans-resveratrol in the presence of 5.5 mM glucose did not affect any of the biomarkers investigated. Incubation of ARPE-19 cells with 33 mM glucose for 9 days significantly induced the accumulation of VEGF, IL-6, IL-8, TGF-beta, and COX-2, activation of PKCbeta, and reduction of Cx43 and GJIC. Incubation of ARPE-19 cells with 33 mM glucose in the presence of 0-10 microM trans-resveratrol dose-dependently inhibited VEGF, TGF-beta1, COX-2, IL-6, and IL 8 accumulation, PKCbeta activation, and Cx43 degradation and enhanced GJIC. These data suggest that trans-resveratrol can protect the retinal pigment epithelial cells against hyperglycemia-induced low-grade inflammation and GJIC degradation. PMID- 20578706 TI - Non-isoflavone phytochemicals in soy and their health effects. AB - Epidemiological and clinical studies have linked consumption of soy foods with low incidences of a number of chronic diseases, such as cardiovascular diseases, cancer, and osteoporosis. Over the past decades, enormous research efforts have been made to identify bioactive components in soy. Isoflavones and soy protein have been suggested as the major bioactive components in soy and have received considerable attention. However, there are hundreds of phytochemical components in soybeans and soy-based foods. In recent years, accumulating evidence has suggested that the isoflavones or soy proteins stripped of phytochemicals only reflect certain aspects of health effects associated with soy consumption. Other phytochemicals, either alone or in combination with isoflavones or soy protein, may be involved in the health effects of soy. This review attempts to summarize major non-isoflavone phytochemicals in soy, as well as their bioavailability and health effects. In addition, a brief discussion of components formed during food processing is also included. PMID- 20578707 TI - Ozonolysis of cyclic alkenes as surrogates for biogenic terpenes: primary ozonide formation and decomposition. AB - Alkene ozonolysis reactions proceed through an unstable intermediate, the primary ozonide (POZ). POZ decomposition controls the complex mechanism. We probe the kinetics of primary ozonide decomposition using temperature programmed reaction spectroscopy (TPRS), revealing primary ozonide decomposition barrier heights of 9.1 +/- 0.4, 9.4 +/- 0.4, and 11.9 +/- 1.2 kcal mol(-1) for cyclohexene, 1-methyl cyclohexene, and methylene-cyclohexane, respectively. We compare experimental decomposition spectra with spectral predictions using density functional theory (DFT) to reveal decomposition products resembling vinyl-hydroperoxides and dioxiranes. We do not find evidence of secondary ozonides. Additional computations with DFT, scaled with the TPRS barrier height, yield barrier heights ranging from 9.4 to 12.1 kcal mol(-1) for the four competing decomposition pathways of the 1-methyl-cyclohexene POZ. Entropic differences were minimal, indicating that POZ decomposition branching is controlled purely by enthalpic variations. These kinetic computations were used to calculate a hydroxyl radical yield for 1-methyl-cyclohexene ozonolysis of 0.85 at 298 K. PMID- 20578708 TI - Contribution of the radical-complex mechanism to the rate of the reaction CH(3) + O(2) (+ M) -> CH(3)O(2) (+ M) at high pressures. AB - Earlier experimental studies of the falloff curves of the reaction CH(3) + O(2) (+ M) -> CH(3)O(2) (+ M) in the bath gases M = Ar and N(2) (Fernandes et al., J. Phys. Chem. A 2006, 110, 4442), in addition to the usual behavior of the energy transfer (ET) mechanism, showed first evidence for a participation of the radical complex (RC) mechanism in the reaction at pressures above about 300 bar and at temperatures below 400 K. By extending these measurements to the bath gas M = CO(2), more pronounced deviations from the ET mechanism were now observed. This unambiguously confirms the presence of the RC mechanism at high pressures in a medium-sized molecular system, analogous to earlier observations for larger systems such as the dimerization of benzyl radicals (Luther et al., Phys. Chem. Chem. Phys. 2004, 6, 4133). PMID- 20578709 TI - Trace of the thermally induced evolution mechanism of interactions between water and ionic liquids. AB - The thermally induced evolution mechanisms of various interactions in ionic liquids (1-butyl-3-methylimidazolium tetrafluoroborate, bmimBF(4)) and water mixtures have been investigated in this paper. In the near-infrared (NIR) spectroscopy, we focus mainly on nu(OH) and nu(CH) overtone regions. During heating of bmimBF(4) and water mixtures, the nu(OH) overtone peak shows a significant blue shift, and the area of this peak shows different changes in three heating regions. By using the perturbation correlation moving window (PCMW) method, we have ascertained the critical temperatures of these three regions: 25 100, 105-160, and 165-190 degrees C, and we have accordingly performed 2D correlation NIR analysis in three parts. On the basis of 2D study results, we find several types of O-H involved hydrogen bonds (H-B's) in a bmimBF(4) and water (15 mol %) mixture and arrive at their evolution mechanisms in each heating region. During heating at 25-100 degrees C, strong H-B's, such as BF(4)( )...water...BF(4)(-) and BF(4)(-)...cyclic water dimer...BF(4)(-), transform into weaker H-B's with simpler structures; at 105-160 degrees C, the remaining BF(4)( )...water...BF(4)(-) continues to dissociate, and cation...water H-B's start to dissociate, and a large amount of released free water evaporates; whereas in the final heating region of 165-190 degrees C, BF(4)(-)...water...BF(4)(-) still exists and continues to dissociate, and in the study of the nu(CH) overtone region, we have found that the concentration of water in bmimBF(4) affects interactions between cations and anions. In the mixture of bmimBF(4) with more water (15 mol %), H-B's between water and bmimBF(4) cannot be completely destroyed, even at very high temperature; therefore, only limited new electrostatic interactions would be formed between cations and anions during heating, but in a mixture of bmimBF(4) with less water (15 mol %), cations and anions are able to form new electrostatic interactions during the heating process. However, the intensity of these interactions is smaller than that in the 80 degrees C isothermal process due to the low contacting possibilities among ions at high temperatures. PMID- 20578710 TI - Network-enhanced photoresponse time of Ge nanowire photodetectors. AB - We demonstrated that the photoresponse time of Ge nanowire (NW) photodetectors could be greatly improved by using percolated NW networks (instead of single NW) as the active detection channels. Although the reset time for single-NW devices was >70 s, a fast reset time <1 s was observed for NW-network devices. The enhancement was attributed to the barrier-dominated conductance for network devices, which was not available in single-NW devices. The network structures provide ideal alternative solutions to the conventional single-NW photodetectors, given their superior performances and low-cost fabrication processes. PMID- 20578711 TI - Solution phase synthesis of a combinatorial library of chalcones and flavones as potent cathepsin V inhibitors. AB - Cathepsin V is a papain-like cysteine protease. It is involved in the control of human T cells (responsible for cell immunity), and presents the largest elastolytic activity among the proteolytic enzymes. Therefore, cathepsin V is a potential molecular target for the treatment of atherosclerosis. In the present work, natural flavonoids were screened against cathepsin V, and two flavones were identified as potent inhibitors of cathepsin V. On the basis of this result, a combinatorial library of chalcones and flavones was prepared, in solution phase employing a scavenger reagent, and fully evaluated. PMID- 20578712 TI - Selection of in silico drug screening results by using universal active probes (UAPs). AB - We developed a new method that uses a set of drug-like compounds to select reliable in silico drug screening results. If some active compounds are known, the screening results that rank these active compounds at the top should be reliable. If no active compound is known, how to select the result is in question. We propose a concept of a set of "universal active probes" (UAPs), which is a set of small active compounds that bind to different kinds of proteins. We found that the hit ratio of the true active compounds in in silico screening shows positive correlation to that of the UAPs, probably because UAPs form a set of drug-like compounds. Thus, if the UAPs were added to the compound library, the screening result that shows a high hit ratio of the UAPs could give reliable actual hit compounds for the target protein. We examined this method for several targets and found this idea useful. PMID- 20578713 TI - Theoretical study of M(+)-RG and M(2+)-RG complexes and transport of M(+) through RG (M = Be and Mg, RG = He-Rn). AB - We present high level ab initio potential energy curves for the M(n+)-RG complexes, where n = 1, 2, RG = rare gas, and M = Be and Mg. Spectroscopic constants have been derived from these potentials, and they generally show very good agreement with the available experimental data. The potentials have also been employed in calculating transport coefficients for M(+) moving through a bath of RG atoms, and the isotopic scaling relationship is examined for Mg(+) in Ne. Trends in binding energies, D(e), and bond lengths, R(e), are discussed and compared to similar ab initio results involving the corresponding complexes of the heavier alkaline earth metal ions. We identify some very unusual behavior, particularly for Be(+)-Ne, and offer possible explanations. PMID- 20578714 TI - Isolation, structure elucidation, and synergistic antibacterial activity of a novel two-component lantibiotic lichenicidin from Bacillus licheniformis VK21. AB - A novel synergetic lantibiotic pair, Lchalpha (3249.51 Da) and Lchbeta (3019.36 Da), termed lichenicidin VK21, was isolated from the producer strain Bacillus licheniformis VK21. Chemical and spatial structures of Lchalpha and Lchbeta were determined. Each peptide contains 31 amino acid residues linked by 4 intramolecular thioether bridges and the N-terminal 2-oxobutyryl group. Spatial structures of Lchalpha and Lchbeta were studied by NMR spectroscopy in methanol solution. The Lchalpha peptide displays structural homology with mersacidin-like lantibiotics and involves relatively well-structured N- and C-terminal domains connected by a flexible loop stabilized by a thioether bridge Ala11-S-Ala21. In contrast, the Lchbeta peptide represents a prolonged hydrophobic alpha-helix flanked with more flexible N- and C-terminal domains. A lantibiotic cluster of the Bacillus licheniformis VK21 genome which comprises the structural genes, lchA1 and lchA2, encoding the lantibiotics precursors, as well as the gene of a modifying enzyme lchM1, was amplified and sequenced. The mature peptides, Lchalpha and Lchbeta, interact synergistically to possess antibiotic activity against Gram-positive bacteria within a nanomolar concentration range, though the individual peptides were shown to be active at micromolar concentrations. Our results afford molecular insight into the mechanism of lichenicidin VK21 action. PMID- 20578715 TI - Absorption spectrum, mass spectrometric properties, and electronic structure of 1,2-benzoquinone. AB - Absorption spectrophotometric and mass spectrometric properties of 1,2 benzoquinone, prepared in aqueous solution by the hexachloroiridate(IV) oxidation of catechol and isolated by HPLC, are reported. Its absorption spectrum has a broad moderately intense band in the near UV with an extinction coefficient of 1370 M(-1)cm(-1) at its 389 nm maximum. The oscillator strength of this band contrasts with those of the order-of-magnitude stronger approximately 250 nm bands of most 1,4-benzoquinones. Gaussian analysis of its absorption spectrum indicates that it also has modestly intense higher energy bands in the 250-320 nm region. In atmospheric pressure mass spectrometric studies 1,2-benzoquinone exhibits very strong positive and negative mass 109 signals that result from the addition of protons and hydride ions in APCI and ESI ion sources. It is suggested that the hydride adduct is formed as the result of the highly polar character of ortho-quinone. On energetic collision the hydride adduct loses an H atom to produce the 1,2-benzosemiquinone radical anion. The present studies also show that atmospheric pressure mass spectral patterns observed for catechol are dominated by signals of 1,2-benzoquinone resulting from oxidation of catechol in the ion sources. Computational studies of the electronic structures of 1,2 benzoquinone, its proton and hydride ion adducts, and 1,2-benzosemiquinone radical anion are reported. These computational studies show that the structures of the proton and hydride adducts are similar and indicate that the hydride adduct is the proton adduct of a doubly negatively charged 1,2-benzoquinone. The contrast between the properties of 1,2- and 1,4-benzoquinone provides the basis for considerations on the effects of conjugation in aromatic systems. PMID- 20578716 TI - Widely differing photochemical behavior in related octahedral {Ru-NO}6 compounds: intramolecular redox isomerism of the excited state controlling the photodelivery of NO. AB - trans-[(NC)Ru(py)(4)(mu-CN)Ru(py)(4)(NO)](3+) (py = pyridine) is a stable species in aqueous solution. It displays an intense absorption in the visible region of the spectrum (lambda(max) = 518 nm; epsilon(max) = 6100 M(-1) cm(-1)), which turns this compound into a promising agent for the photodelivery of NO. The quantum yield for the photodelivery process resulting from irradiation with 455 nm visible light was found experimentally to be (0.06 +/- 0.01) x 10(-3) mol einstein(-1), almost 3 orders of magnitude smaller than that in the closely related cis-[RuL(NH(3))(4)(mu-pz)Ru(bpy)(2)(NO)](5+) species (L = NH(3) or pyridine, pz = pyrazine, bpy = 2,2'-bipyridine; phi(NO) = 0.02-0.04 mol einstein( 1) depending on L) and also much smaller than the one in the mononuclear compound trans-[ClRu(py)(4)(NO)](2+) (phi(NO) = (1.63 +/- 0.04) x 10(-3) mol einstein( 1)). DFT computations provide an electronic structure picture of the photoactive excited states that helps to understand this apparently abnormal behavior. PMID- 20578717 TI - Hydrothermal synthesis and characterization of LiREF4 (RE = Y, Tb-Lu) nanocrystals and their core-shell nanostructures. AB - In this paper, a water-ethanol-oleic acid system was developed to prepare LiREF(4) nanocrystals with a controlled size and shape. The influence of LiOH concentration and temperature on the phase and shape evolution of the LiREF(4) nanocrystals was systematically investigated and discussed. It was found that the LiOH concentration was the key factor responsible for the shape evolution and phase control for LiREF(4) nanocrystals at selected temperatures. The LiYF(4) LiLuF(4) core-shell nanostructure was synthesized and characterized. PMID- 20578718 TI - Predictors of serum dioxin, furan, and PCB concentrations among women from Chapaevsk, Russia. AB - Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs. PMID- 20578719 TI - In vitro protective effects of two extracts from bergamot peels on human endothelial cells exposed to tumor necrosis factor-alpha (TNF-alpha). AB - Bergamot ( Citrus bergamia Risso) is a less commercialized Citrus fruit, mainly used for its essential oil extracted from the peel. Bergamot peel (BP) represents about 60% of the processed fruits and is regarded as primary waste. However, it contains good amounts of useful compounds, such as pectins and flavonoids. Many of the bioactivities of Citrus flavonoids appear to impact vascular endothelial cells. Herein, we report the protective effect of two flavonoid-rich extracts from BP (endowed with radical-scavenging properties and lacking genotoxic activity) against alterations in cell modifications induced by the pleiotropic inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) on human umbilical vein endothelial cells (HUVECs), as demonstrated by monitoring intracellular levels of malondialdehyde/4-hydroxynonenal, reduced and oxidized glutathione and superoxide dismutase activity, and the activation status of nuclear factor-kappaB (NF-kappaB). Thus, BP appears to be a potential source of natural antioxidant/anti-inflammatory phytocomplexes to be employed as ingredients of nutraceutical products or functional foods. PMID- 20578720 TI - Theoretical calculation of the magnetic resonance parameters of trigonal prismatic tris(o-aminobenzenethiol)technetium and -rhenium complexes. AB - Spin Hamiltonian parameters for the neutral trigonal-prismatic Tc(abt)(3) and Re(abt)(3) chelates (abt = o-aminobenzenethiol) are calculated using relativistic density functional theory at the all-electron level. The small magnitude of the calculated g shifts and metal hyperfine interactions is in excellent agreement with previous experimental predictions based upon a ligand-centered ground-state magnetic orbital. The theoretical (14)N ligand hyperfine and quadrupole couplings also reproduce the nuclear frequencies measured by electron spin-echo envelope modulation spectroscopy. The nuclear quadrupole interaction of (187)Re is predicted to be 2 orders of magnitude larger than that of (99)Tc, in agreement with empirical simulation of the continuous-wave electron paramagnetic resonance spectrum. The spectrum of Tc(abt)(3) at high solute concentrations contains a central resonance not predicted for the isolated complex by theoretical calculations. The absence of this resonance at low solute concentrations provides evidence of intermolecular interactions in these systems. PMID- 20578721 TI - Oxygenation chemistry at a mononuclear copper(II) hydroquinone system with O2. AB - Aerobic treatment of a copper(II) complex supported by a bis(pyridin-2 ylmethyl)amine ligand containing a p-hydroquinone moiety on one of the pyridine donor groups in CH(3)OH induces oxygenation reaction of the ligand to give a hydroxylated p-quinone derivative. PMID- 20578722 TI - Quantifying the impact of chimera MS/MS spectra on peptide identification in large-scale proteomics studies. AB - A complicating factor for protein identification within complex mixtures by LC/MS/MS is the problem of "chimera" spectra, where two or more precursor ions with similar mass and retention time are co-sequenced by MS/MS. Chimera spectra show reduced scores due to unidentifiable fragment ions derived from contaminating parents. However, the extent of chimeras in LC/MS/MS data sets and their impact on protein identification workflows are incompletely understood. We report ChimeraCounter, a software program which detects chimeras in data sets collected on an Orbitrap/LTQ instrument. Evaluation of synthetic chimeras created from pairs of well-defined peptide MS/MS spectra reveal that chimeras reduce database search scores most significantly when contaminating fragment ion intensities exceed 20% of the targeted fragment ion intensities. In large-scale data sets, the identification rate for chimera MS/MS is 2-fold lower compared to nonchimera spectra. Importantly, this occurs in a manner which depends not on absolute precursor ion intensity, but on intensity relative to the median precursor intensity distribution. We further show that chimeras reduce the number of accepted peptide identifications by increasing false negatives while showing little increase in false positives. The results provide a framework for identifying chimeras and characterizing their contribution to the poorly understood false negative class of MS/MS. PMID- 20578724 TI - Structural and kinetic study of the extended active site for proton transfer in human carbonic anhydrase II. AB - The catalysis of CO(2) hydration by human carbonic anhydrase II (HCA II) is limited in maximal velocity by proton transfer from a zinc-bound water molecule to the proton shuttle His64. This proton transfer occurs along a hydrogen-bonded water network, leading to the proton shuttle residue His64, which in turn transfers the proton to bulk solvent. The side chain of His64 occupies two conformations in wild-type HCA II, pointing inward toward the zinc or outward toward bulk solvent. Previously, several studies have examined the roles of residues of the active site cavity that interact with the solvent-mediated hydrogen-bonded network between His64 and the zinc-bound water. Here these studies are extended to examine the effects on proton transfer by mutation at Lys170 (to Ala, Asp, Glu, and His), a residue located near the side chain of His64 but over 15 A away from the active site zinc. In all four variants, His64 is observed in the inward conformation associated with a decrease in the pK(a) of His64 by as much as 1.0 unit and an increase in the rate constant for proton transfer to as much as 4 micros(-1), approximately 5-fold larger than wild-type HCA II. The results show a significant extension of the effective active site of HCA II from the zinc-bound water at the base of the conical cavity in the enzyme to Lys170 near the rim of the cavity. These data emphasize that the active site of HCA II is extended to include residues that, at first glance, appear to be too far from the zinc to exert any catalytic effects. PMID- 20578723 TI - Ultrafast ultraviolet photodissociation at 193 nm and its applicability to proteomic workflows. AB - Ultraviolet photodissociation (UVPD) at 193 nm was implemented on a linear ion trap mass spectrometer for high-throughput proteomic workflows. Upon irradiation by a single 5 ns laser pulse, efficient photodissociation of tryptic peptides was achieved with production of a, b, c, x, y, and z sequence ions, in addition to immonium ions and v and w side-chain loss ions. The factors that influence the UVPD mass spectra and subsequent in silico database searching via SEQUEST were evaluated. Peptide sequence aromaticity and the precursor charge state were found to influence photodissociation efficiency more so than the number of amide chromophores, and the ion trap q-value and number of laser pulses significantly affected the number and abundances of diagnostic product ions (e.g., sequence and immonium ions). Also, photoionization background subtraction was shown to dramatically improve SEQUEST results, especially when peptide signals were low. A liquid chromatography-mass spectrometry (LC-MS)/UVPD strategy was implemented and yielded comparable or better results relative to LC-MS/collision induced dissociation (CID) for analysis of proteolyzed bovine serum albumin and lysed human HT-1080 cytosolic fibrosarcoma cells. PMID- 20578725 TI - Zebrafish (Danio rerio) endomembrane antiporter similar to a yeast cation/H(+) transporter is required for neural crest development. AB - CAtion/H(+) eXchangers (CAXs) are integral membrane proteins that transport Ca(2+) or other cations by exchange with protons. While several yeast and plant CAX proteins have been characterized, no functional analysis of a vertebrate CAX homologue has yet been reported. In this study, we further characterize a CAX from yeast, VNX1, and initiate characterization of a zebrafish CAX (Cax1). Localization studies indicated that both Vnx1 and Cax1 proteins are found in endomembrane compartments. Biochemical characterization of endomembrane fractions from vnx1 mutant cells and zebrafish Cax1-expressing yeast cells suggested that both yeast and fish CAXs have Ca(2+)/H(+) antiport activities. Additionally, the vnx1 mutation was associated with heightened pH-sensitivity. In zebrafish embryos, cax1 was specifically expressed in neural crest cells. Morpholino knockdown of cax1 caused defects in neural crest development, including alterations in pigmentation, defects in jaw development, and reduction in expression of the neural crest marker, Pax7. Collectively, our findings provide insights into Vnx1 function and support an unexpected role of CAX transporters in animal growth and development. PMID- 20578726 TI - Properties of a metal clad waveguide sensor based on a nanoporous-metal oxide/metal multilayer film. AB - A metal-clad waveguide (MCWG) sensor comprised of a nanoporous waveguiding layer on a metal cladding layer is advantageous in sensing of biomolecules because of a high surface area of nanopores and a sharp dip in the reflection spectrum due to characteristics of the MCWG mode. Here, a porous anodic alumina (PAA)/aluminum (Al) film was fabricated on a glass substrate as a MCWG sensor with the Kretschmann geometry, and the sensor response was examined for both colorless bovine serum albumin (BSA) and colored metal complexes by measurements of reflection spectra and Fresnel calculations. The BSA adsorption on the PAA layer induced a parallel redshift of the waveguide coupling dip in the reflection spectrum. The experimental results were well simulated by the five-phase Fresnel calculations which indicated that the redshift of the dip was linearly dependent on the adsorbed amount of BSA. When the response of a MCWG sensor with a PAA layer was compared with that of a MCWG sensor with a nonporous alumina layer, the former showed larger redshift than the latter, due to a large adsorbed amount of BSA in the PAA layer with high surface area. For the adsorption of colored Ru[Bphen(3)](2+) and Fe[Phen(3)](2+), the effect of both the real and imaginary parts of the complex refractive index on the sensor response was examined. As a result, a redshift of the waveguide coupling dip was observed for both metal complexes irrespective of the wavelength region examined; this could be ascribed to the changes in the real part of the refractive index due to the adsorption of metal complexes on the PAA layer. Meanwhile, an increase in the reflectivity was observed when the coupling wavelength was close to that of the absorption bands of the metal complexes; this could be ascribed to the changes in the imaginary part of the refractive index of the PAA layer. Using the sensor response caused by the changes in the imaginary part, absorption spectral profiles of metal complexes could be reproduced. PMID- 20578727 TI - Estimation of ADME properties with substructure pattern recognition. AB - Over the past decade, absorption, distribution, metabolism, and excretion (ADME) property evaluation has become one of the most important issues in the process of drug discovery and development. Since in vivo and in vitro evaluations are costly and laborious, in silico techniques had been widely used to estimate ADME properties of chemical compounds. Traditional prediction methods usually try to build a functional relationship between a set of molecular descriptors and a given ADME property. Although traditional methods have been successfully used in many cases, the accuracy and efficiency of molecular descriptors must be concerned. Herein, we report a new classification method based on substructure pattern recognition, in which each molecule is represented as a substructure pattern fingerprint based on a predefined substructure dictionary, and then a support vector machine (SVM) algorithm is applied to build the prediction model. Therefore, a direct connection between substructures and molecular properties is built. The most important substructure patterns can be identified via the information gain analysis, which could help to interpret the models from a medicinal chemistry perspective. Afterward, this method was verified with two data sets, one for blood-brain barrier (BBB) penetration and the other for human intestinal absorption (HIA). The results demonstrated that the overall predictive accuracies of the best HIA model for the training and test sets were 98.5 and 98.8%, and the overall predictive accuracies of the best BBB model for the training and test sets were 98.8 and 98.4%, which confirmed the reliability of our method. In the additional validations, the predictive accuracies were 94 and 69.5% for the HIA and the BBB models, respectively. Moreover, some of the representative key substructure patterns which significantly correlated with the HIA and BBB penetration properties were also presented. PMID- 20578728 TI - Insights for predicting blood-brain barrier penetration of CNS targeted molecules using QSPR approaches. AB - Due to the high attrition rate of central nervous system drug candidates during clinical trials, the assessment of blood-brain barrier (BBB) penetration in early research is particularly important. A genetic approximation (GA)-based regression model was developed for predicting in vivo blood-brain partitioning data, expressed as logBB (log[brain]/[blood]). The model was built using an in-house data set of 193 compounds assembled from 22 different therapeutic projects. The final model (cross-validated r(2) = 0.72) with five molecular descriptors was selected based on validation using several large internal and external test sets. We demonstrate the potential utility of the model by applying it to a set of literature reported secretase inhibitors. In addition, we describe a rule-based approach for rapid assessment of brain penetration with several simple molecular descriptors. PMID- 20578729 TI - Comparison of the in vitro replication of the 7-(2-oxoheptyl)-1,N2-etheno-2' deoxyguanosine and 1,N2-etheno-2'-deoxyguanosine lesions by Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). AB - Oligonucleotides were synthesized containing the 7-(2-oxoheptyl)-etheno-dGuo adduct, which is derived from the reaction of dGuo and the lipid peroxidation product 4-oxo-2-nonenal. The in vitro replication of 7-(2-oxoheptyl)-etheno-dGuo by the model Y-family polymerase Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4) was examined in two sequences. The extension products were sequenced using an improved LC-ESI-MS/MS protocol developed in our laboratories, and the results were compared to that of the 1,N(2)-etheno-dGuo adduct in the same sequence contexts. Both etheno adducts were highly miscoding when situated in 5'-TXG-3' local sequence contexts with <4% of the extension products being derived from error-free bypass. The major extension products resulted from the misinsertion of Ade opposite the adduct and a one-base deletion. The major extension products from replication of the etheno lesions in a 5'-CXG-3' local sequence context were the result of misinsertion of Ade, a one-base deletion, and error-free bypass. Other minor extension products were also identified. The 7-(2-oxoheptyl)-etheno dGuo lesion resulted in a larger frequency of misinsertion of Ade, whereas the 1,N(2)-etheno-dGuo gave more of the one-base deletion product. Conformational studies of duplex DNA containing the 7-(2-oxoheptyl)-etheno-dGuo in a 5'-TXG-3' sequence context by NMR indicated the presence of a pH-dependent conformational transition, likely involving the glycosyl bond at the adducted guanosine; the pK(a) for this transition was lower than that observed for the 1,N(2)-epsilon dGuo lesion. However, the 7-(2-oxoheptyl)-etheno-dGuo lesion, the complementary Cyt, and both flanking base pairs remained disordered at all pH values, which is attributed to the presence of the hydrophobic heptyl group of the 7-(2-oxoheptyl) etheno-dGuo lesion. The altered pK(a) value and the structural disorder at the 7 (2-oxoheptyl)-etheno-dGuo lesion site, as compared to the same sequence containing the 1,N(2)-etheno-dGuo, may contribute to higher frequency of misinsertion of Ade. PMID- 20578731 TI - Identification of N-glycosylation changes in the CSF and serum in patients with schizophrenia. AB - Schizophrenia is a major neuropsychiatric disorder that affects 2% of the population worldwide. No biochemical diagnostic tests are available, and patients must undergo lengthy clinical evaluation periods before an accurate diagnosis can be given. Blood and cerebrospinal fluid are candidates for the identification of potential biomarkers for this disease. We have identified several N-glycans that distinguish first onset, unmedicated schizophrenia patients from healthy individuals. This is the first report of the N-glycome from low abundance serum proteins and cerebrospinal fluid. The tetraantennary tetrasialylated glycan with a polylactosamine extension, A4G4LacS4, from low abundance serum proteins showed a 2-fold increase in serum from male schizophrenia patients. Gender specificity was also demonstrated as the triantennary trisialylated glycan containing the SLex epitope was increased significantly in male schizophrenia patients on both high and low abundance serum proteins. Levels of bisecting and sialylated glycans in the cerebrospinal fluid showed a general down-regulation in schizophrenia patients and a 95% positive predictive power for distinguishing patients from controls. These changes are consistent with the reported down-regulation of beta 1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase III and beta galactoside alpha-2,3/6-sialyltransferases in the prefrontal cortex from schizophrenia patients. These alterations in the N-glycosylation signature could be used potentially for early diagnosis and monitoring of patients after treatment. PMID- 20578730 TI - Development of an annotated library of neutral human milk oligosaccharides. AB - Human milk oligosaccharides (HMOs) perform a number of functions including serving as prebiotics to stimulate the growth of beneficial intestinal bacteria, as receptor analogues to inhibit binding of pathogens, and as substances that promote postnatal brain development. There is further evidence that HMOs participate in modulating the human immune system. Because the absorption, catabolism, and biological function of oligosaccharides (OS) have strong correlations with their structures, structure elucidation is key to advancing this research. Oligosaccharides are produced by competing enzymes that provide the large structural diversity and heterogeneity that characterizes this class of compounds. Unlike the proteome, there is no template for oligosaccharides, making it difficult to rapidly identify oligosaccharide structures. In this research, annotation of the neutral free oligosaccharides in milk is performed to develop a database for the rapid identification of oligosaccharide structures. Our strategy incorporates high performance nanoflow liquid chromatography and mass spectrometry for characterizing HMO structures. HPLC-Chip/TOF MS provides a sensitive and quantitative method for sample profiling. The reproducible retention time and accurate mass can be used to rapidly identify the OS structures in HMO samples. A library with 45 neutral OS structures has been constructed. The structures include information regarding the epitopes such as Lewis type, as well as information regarding the secretor status. PMID- 20578733 TI - Tailorable thiolated trimethyl chitosans for covalently stabilized nanoparticles. AB - A novel four-step method is presented to synthesize partially thiolated trimethylated chitosan (TMC) with a tailorable degree of quaternization and thiolation. First, chitosan was partially N-carboxylated with glyoxylic acid and sodium borohydride. Next, the remaining amines were quantitatively dimethylated with formaldehyde and sodium borohydride and then quaternized with iodomethane in NMP. Subsequently, these partially carboxylated TMCs dissolved in water were reacted with cystamine at pH 5.5 using EDC as coupling agent. After addition of DTT and dialysis, thiolated TMCs were obtained, varying in degree of quaternization (25-54%) and degree of thiolation (5-7%), as determined with (1)H NMR and Ellman's assay. Gel permeation chromatography with light scattering detection indicated limited intermolecular cross-linking. All thiolated TMCs showed rapid oxidation to yield disulfide cross-linked TMC at pH 7.4, while the thiolated polymers were rather stable at pH 4.0. When Calu-3 cells were used, XTT and LDH cell viability tests showed a slight reduction in cytotoxicity for thiolated TMCs as compared to the nonthiolated polymers with similar DQs. Positively charged nanoparticles loaded with fluorescently labeled ovalbumin were made from thiolated TMCs and thiolated hyaluronic acid. The stability of these particles was confirmed in 0.8 M NaCl, in contrast to particles made from nonthiolated polymers that dissociated under these conditions, demonstrating that the particles were held together by intermolecular disulfide bonds. PMID- 20578732 TI - Proteomic profile of uterine luminal fluid from early pregnant ewes. AB - Embryonic development is a time-sensitive period that requires a synchronized uterine environment, which is created by the secretion of proteins from both the embryo and uterus. Numerous studies have identified uterine luminal proteins and related these to specific adaptations during early pregnancy (EP). However, no study has yet utilized LC-MS/MS to identify the signature profile of proteins in the uterine lumen during EP. In this study, uterine luminal fluid from nonpregnant (NP; n = 3) and EP (n = 3; gestational day 16) ewes were analyzed by LC-MS/MS and validated by Western immunoblotting. We identified a unique signature profile for EP luminal fluid; 15 proteins related to specific aspects of embryonic development including growth and remodeling, immune system regulation, oxidative stress balance, and nutrition were significantly altered (up to 65-fold of NP) in EP profile. Specific uterine remodeling proteins such as transgelin (P = 0.008) and placental proteins like PP9 (P = 0.02) were present in EP luminal fluid but were barely detectable in the NP flushings. Direct correlations (R(2) = 0.84, P = 0.01) were observed between proteomics and immunoblotting. These data provide information on dynamic physiological processes associated with EP at the level of the uterus and conceptus and may potentially demonstrate a signature profile associated with embryonic well-being. PMID- 20578734 TI - Are PBDEs an environmental equity concern? Exposure disparities by socioeconomic status. PMID- 20578735 TI - Reducing humanity's water footprint. PMID- 20578736 TI - After the oil is no longer leaking.. . PMID- 20578737 TI - Transport and kinetic studies to characterize reactive and nonreactive sites on granular iron. AB - To better understand controls on observed trichloroethene (TCE) reaction rates in granular iron permeable reactive barriers, column experiments were conducted with different iron loadings. Using a reactive transport model and the Kinetic Iron Model (KIM), unique estimates of Langmuir sorption parameters for both the nonreactive and reactive sites, and a rate constant for TCE reduction on the iron surface provides new insights into the character of granular iron that determines overall reactivity. Nonreactive isotherms found in this work compared well with literature isotherms, and it was also found that for TCE and Connelly iron, only about 2% of sorption occurred to reactive sites, in agreement with earlier work by others. Thus, the KIM parameters were found to be relevant and useful under the conditions of these experiments. PMID- 20578738 TI - A heteronuclear zero quantum coherence Nz-exchange experiment that resolves resonance overlap and its application to measure the rates of heme binding to the IsdC protein. AB - Chemical exchange phenomena in NMR spectra can be quantitatively interpreted to measure the rates of ligand binding, as well as conformational and chemical rearrangements. In macromolecules, processes that occur slowly on the chemical shift time scale are frequently studied using 2D heteronuclear ZZ or N(z) exchange spectroscopy. However, to successfully apply this method, peaks arising from each exchanging species must have unique chemical shifts in both dimensions, a condition that is often not satisfied in protein-ligand binding equilibria for (15)N nuclei. To overcome the problem of (15)N chemical shift degeneracy we developed a heteronuclear zero-quantum (and double-quantum) coherence N(z) exchange experiment that resolves (15)N chemical shift degeneracy in the indirect dimension. We demonstrate the utility of this new experiment by measuring the heme binding kinetics of the IsdC protein from Staphylococcus aureus. Because of peak overlap, we could not reliably analyze binding kinetics using conventional methods. However, our new experiment resulted in six well-resolved systems that yielded interpretable data. We measured a relatively slow k(off) rate of heme from IsdC (<10 s(-1)), which we interpret as necessary so heme loaded IsdC has time to encounter downstream binding partners to which it passes the heme. The utility of using this new exchange experiment can be easily expanded to (13)C nuclei. We expect our heteronuclear zero-quantum coherence N(z)-exchange experiment will expand the usefulness of exchange spectroscopy to slow chemical exchange events that involve ligand binding. PMID- 20578739 TI - Probing platinum-adenine-n3 adduct formation with DNA minor-groove binding agents. AB - Me-lex(py/py), an adenine-N3-selective alkylating agent, and the reversible minor groove binder netropsin were used to probe the formation of unusual minor-groove adducts by the cytotoxic hybrid agent PT-ACRAMTU ([PtCl(en)(ACRAMTU)](NO(3))(2); en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3 dimethylthiourea). PT-ACRAMTU was found by chemical footprinting to inhibit specific Me-lex-mediated DNA cleavage at several adenine sites but not at nonspecific guanine, which is consistent with the platination of adenine-N3. In a cell proliferation assay, a significant decrease in cytotoxicity was observed for PT-ACRAMTU, when cancer cells were pretreated with netropsin, suggesting that minor-groove adducts in cellular DNA contribute to the biological activity of the hybrid agent. PMID- 20578740 TI - Reversible biological Birch reduction at an extremely low redox potential. AB - The Birch reduction of aromatic rings to cyclohexadiene compounds is widely used in chemical synthesis and requires solvated electrons, the most potent reductants known in organic chemistry. Benzoyl-coenzyme A (CoA) reductases (BCR) are key enzymes in the anaerobic bacterial degradation of aromatic compounds and catalyze an analogous reaction under physiological conditions. Class I BCRs are FeS enzymes and couple the reductive dearomatization of benzoyl-CoA to cyclohexa-1,5 diene-1-carboxyl-CoA (dienoyl-CoA) to a stoichiometric ATP hydrolysis. Here, we report on a tungsten-containing class II BCR from Geobacter metallireducens that catalyzed the fully reversible, ATP-independent dearomatization of benzoyl-CoA to dienoyl-CoA. BCR additionally catalyzed the disproportionation of dienoyl-CoA to benzoyl-CoA/monoenoyl-CoA and the four- and six-electron reduction of benzoyl-CoA in the presence of a reduced low-potential bridged 2,2'-bipyridyl redox dye. Reversible redox titration experiments in the presence of this redox dye revealed a midpoint potential of E(0)' = -622 mV for the benzoyl-CoA/dienoyl-CoA couple, which is far below the values of other known reversible substrate/product redox couples in enzymology. This work demonstrates the efficiency of reversible metalloenzyme catalysis, which in chemical synthesis can only be achieved under essentially irreversible conditions. PMID- 20578741 TI - SnSe nanocrystals: synthesis, structure, optical properties, and surface chemistry. AB - The colloidal synthesis of SnSe nanoparticles is accomplished through the injection of bis[bis(trimethylsilyl)amino]tin(II) into hot trioctylphosphine:selenium in the presence of oleylamine. Through the manipulation of reaction temperature particles are grown with the average diameter reliably tuned to 4-10 nm. Quantum confinement is examined by establishing a relationship between particle size and band gap while the in depth growth dynamics are illuminated through UV-vis-NIR spectroscopy. Surface chemistry effects are explored, including the demonstration of useful ligand exchanges and the development of routes toward anisotropic particle growth. Finally, transient current-voltage properties of SnSe nanocrystal films in the dark and light are examined. PMID- 20578742 TI - Correlation between the photoluminescence and oriented attachment growth mechanism of CdS quantum dots. AB - Water-soluble mercaptoacetic acid-coated 3.1 nm CdS quantum dots (QDs) with two concentrations were selected for studying the correlation between the photoluminescence and the crystal growth mechanism. By achieving the classic Ostwald ripening mechanism and oriented attachment (OA) growth mechanism, we have shown that the evolution of the emission spectra were obviously different. The change in both the surface and internal defects during OA crystal growth were responsible for the specific variation of the photoluminescence of CdS QDs. Strategies for obtaining QDs with different luminescent properties are suggested. PMID- 20578743 TI - Transmission electron microscopy evidence of spontaneous B-cation layered distribution in NaNb(1-x)Ta(x)O3. AB - A transmission electron microscopy (TEM) study of the complex NaNb(1-x)Ta(x)O(3) (0.4 < or = x < or = 0.6) perovskites, combining high-resolution TEM and high angle annular dark-field scanning TEM, has revealed the formation of extended areas on the crystals where niobium and tantalum order into layers in a 1:1 ratio. NaNb(1-x)Ta(x)O(3) oxides are stoichiometric, and there is neither charge difference nor significant ionic size discrepancy between Nb(V) and Ta(V) cations. As d(0) octahedrally coordinated cations, they show a propensity to second-order Jahn-Teller distortion. This distortion, however, manifests itself to different extents for the two cations and is considered the driving force for the layered ordered distribution observed. The niobium-tantalum segregation we have found can also be interpreted as a naturally occurring nanometer-scale phase separation. Albeit occurring in wide regions of the crystals and not in the entire grains, it shows a clear trend toward a long-range ordered disposition. This is reminiscent of the more general behavior of a recently documented class of perovskites that suffer spontaneous nanoscale phase separation to form a superlattice. PMID- 20578744 TI - Cellular response of Fusarium oxysporum to crocidolite asbestos as revealed by a combined proteomic approach. AB - Cellular mechanisms of asbestos toxicity rely, at least in part, on the chemical composition of these minerals. Iron ions are directly involved in the accepted mechanism of fiber toxicity because they constitute active centers where release of free radicals and reactive oxygen species takes place. Although no current technology is available for the remediation of asbestos polluted sites, the soil fungus Fusarium oxysporum was found to be very effective in iron extraction from crocidolite asbestos in vitro, and to cause a significant reduction in asbestos surface reactivity and oxidative damage to naked DNA. As little information is available on the molecular mechanisms of the fungus-asbestos interactions, a combined proteomic approach that used 2-DE, shotgun and quantitative iTRAQ proteomics was used to investigate the fungal metabolic activities in the presence of crocidolite, an iron-rich type of asbestos. Although global proteomic analyses did not show significant changes in the protein expression pattern of F. oxysporum when exposed to asbestos fibers, some proteins specifically regulated by asbestos suggest up-regulation of metabolic pathways involved in protection from oxidative stress. When compared with the response to crocidolite observed by other authors in human lung epithelial cells, that unlike fungi can internalize the asbestos fibres, a significant difference was the regulation of the pentose phosphate pathway. PMID- 20578745 TI - Asymmetric synthesis of sphinganine and ent-clavaminol [corrected] H. AB - An efficient enantioselective synthesis of sphinganine and ent-clavaminol [corrected] H is reported. These sphingoid-type bases were obtained from commercially available fatty acids using highly enantioselective Ru-catalyzed hydrogenation and organocatalytic electrophilic amination reactions to create the stereogenic centers. PMID- 20578746 TI - Ordered nanoporous silica with periodic 30-60 nm pores as an effective support for gold nanoparticle catalysts with enhanced lifetime. AB - We demonstrate that supermolecular templating allows tuning the pore size of ordered mesoporous materials in the once elusive range from 30 nm to more than 60 nm through simple control of synthetic variables (salt/supermolecule concentration and hydrothermal temperature). Gold nanoparticles (AuNPs) within the extra-large pores exhibit dramatically increased lifetime compared to those located within relatively small mesopores due to the enhanced mass diffusion that suppresses coke deposition on AuNPs. PMID- 20578747 TI - On the breakup of patterned nanoscale copper rings into droplets via pulsed-laser induced dewetting: competing liquid-phase instability and transport mechanisms. AB - Nanolithographically patterned copper rings were synthesized, and the self assembly of the rings into ordered nanoparticle/nanodrop arrays was accomplished via nanosecond pulsed laser heating above the melt threshold. The resultant length scale was correlated to the transport and instability growths that occur during the liquid lifetime of the melted copper rings. For 13-nm-thick rings, a change in the nanoparticle spacing with the ring width is attributed to a transition from a Raleigh-Plateau instability to a thin film instability because of competition between the cumulative transport and instability timescales. To explore the competition between instability mechanisms further, we carried out experiments with 7-nm-thick rings. In agreement with the theoretical predictions, these rings break up in both the azimuthal and radial directions, confirming that a simple hydrodynamic model captures the main features of the processes leading to the breakup. PMID- 20578748 TI - Pyrrole synthesis via allylic sp3 C-H activation of enamines followed by intermolecular coupling with unactivated alkynes. AB - A conceptually novel pyrrole synthesis is reported, efficiently merging enamines and (unactivated) alkynes under oxidative conditions. In an intermolecular Rh catalyzed process, the challenging allylic sp(3) C-H activation of the enamine substrates is followed by the cyclization with the alkyne (R(3) = CO(2)R). Alternatively, in some cases (R(3) = CN), the enamine can be utilized for a vinylic sp(2) C-H activation. A total of 17 examples with yields above 60% is presented, together with the results of an initial mechanistic investigation. PMID- 20578749 TI - 5-N,4-O-carbonyl-7,8,9-tri-O-chloroacetyl-protected sialyl donor for the stereoselective synthesis of alpha-(2-->9)-tetrasialic acid. AB - An efficient stereoselective synthesis of alpha-(2-->9)-tetrasialic acid was achieved using tri-O-chloroacetyl-derivatized sialyl donor and a triol sialyl acceptor. Both the acceptor and the donor were also protected with a cyclic 5-N-4 O-carbonyl protecting group. The donor is highly reactive and enabled alpha selective sialylation with various primary, secondary, and tertiary acceptors under in situ activation conditions (NIS/TfOH, -78 degrees C, acetonitrile/dichloromethane). The trans-fused oxazolidinone ring and O chloroacetyl protecting groups were easily removed under mild reaction conditions to provide the fully deprotected alpha(2-->9)-tetrasialic acid. PMID- 20578750 TI - DNA lipoplexes: formation of the inverse hexagonal phase observed by coarse grained molecular dynamics simulation. AB - Mixtures of dsDNA and lipids, so-called lipoplexes, are widely used as less toxic alternatives to viral vectors in transfection studies. However, the transfection efficiency achieved by lipoplexes is significantly lower than that of viral vectors and is a barrier to their use in the clinic. There is now significant evidence suggesting that the molecular organization and structure (nanoarchitecture) of lipoplexes might correlate with biological activity. As a consequence, the ability to predict quantitatively the nanoarchitecture of new systems, and how these might change intracellularly, would be a major tool in the development of rational discovery strategies for more efficient lipoplex formulations. Here we report the use of a coarse-grain molecular dynamics simulation to predict the phases formed by two lipoplex systems: dsDNA-DOPE and dsDNA-DOPE-DOTAP. The predictions of the simulations show excellent agreement with experimental data from polarized light microscopy and small-angle X-ray diffraction (SAXS); the simulations predicted the formation of phases with d spacings that were comparable to those measured by SAXS. More significantly, the simulations were able to reproduce for the first time the experimentally observed change from a fluid lamellar to an inverse hexagonal phase in the dsDNA-DOPE DOTAP system as a function of changes in lipid composition. Our studies indicate that coarse-grain MD simulations could provide a powerful tool to understand, and hence design, new lipoplex systems. PMID- 20578752 TI - Influence of electrolyte and polymer loadings on mechanical properties of clay aerogels. AB - The effects of electrolyte and polymer loadings on formation, density, and mechanical properties of clay aerogels have been investigated. Coherent aerogels were formed at all tested concentrations except at a combination of low electrolyte (<0.04 M) and polymer (<1% w/v) concentrations because of partial clay flocculation. The compressive modulus and yield strength of the aerogels containing poly(vinyl alcohol) are sensitive to electrolyte loading at low polymer concentration but are otherwise insensitive. Mechanical properties show power law dependence on aerogel density, which depends mainly on polymer loading. The power law exponent for the compressive modulus is 3.74 when the relative density is used in the model and 5.7 when the measured bulk density is used instead. These high exponent values are attributed to the layered microstructure of these aerogels. PMID- 20578751 TI - Viscosity effects on hydrodynamic drainage force measurements involving deformable bodies. AB - Dynamic force measurements have been made between an oil drop and a silica particle in surfactant and sucrose solutions with viscosities that range up to 50 times that of water. These conditions provide variations in the shear rate and the relative time scales of droplet deformation and hydrodynamic drainage in a soft matter system. The results obtained indicate that soft deformable boundaries have a natural response that limits the maximum shear rate that can be sustained in thin films compared to shear rates that can be attained in films bounded by rigid boundaries. In addition, to extend boundary slip studies on rigid surfaces, we use a smooth deformable droplet surface to probe the dependence of the boundary slip on fluid viscosity without the added complications of surface roughness or heterogeneity. Imposing a Navier slip model to characterize possible slip at the deformable oil-sucrose solution interface gives results that are consistent with a slip length of no larger than 10 nm over the range of solution viscosity studied, although an immobile (zero slip length) condition at the oil sucrose solution interface is perfectly adequate. In high viscosity solutions, cantilever motion at high scan rates induces a significant cantilever deflection. A method has been developed to account for this effect in order to extract the correct dynamic force between the deformable drop and the particle. PMID- 20578753 TI - Insight into the phenomenology of the Cr(VI) reduction by metallic iron using an electron probe microanalyzer. AB - Research was performed to gain insight into the heterogeneous reaction of Cr(VI) reduction by zero-valent iron, which is frequently used in the treatment of contaminated groundwater using permeable reactive barriers. An electron probe microanalyzer was used to clarify in detail relevant aspects of the reaction with consequences for the conception of interpretative kinetic models. Spherical particles of iron with controlled grain sizes were used after being subjected to a previous washing with diluted acid in order to remove oxidation products. These spheres were immersed in solutions of Cr(VI) in nonagitated flasks using different operating procedures. The iron particles were photographed so that the time evolution of the grain size distribution could be established. A sample of the iron balls after the reaction and samples of the raw material and the precipitates of the reaction products were analyzed by backscattering electron images and elemental mapping produced by wavelength-dispersive spectroscopy. The analysis of the spatial distribution of the concentrations in iron, oxygen, and chromium indicates that there are three distinct mechanisms for the reaction with different limiting steps. PMID- 20578754 TI - Decomposition of methanthiol on Pt(111): a density functional investigation. AB - Decomposition of methanthiol on Pt(111) is systematically investigated using self consistent periodic density functional theory (DFT), and the decomposition network has been mapped out. The most stable adsorption of the involved species tends to form the sp(3) hybridized configuration of both C and S atoms, in which C is almost tetrahedral and S has the tendency to bond to three atoms. Spontaneous dissociation rather than desorption is preferred for adsorbed methanthiol. Based on the harmonic transition state theory calculations, the decomposition rate constants of the thiolmethoxy and thioformaldehyde intermediates are found to be much lower than those for their formation, leading to long lifetimes of the intermediates for observation. Under the ultrahigh vacuum (UHV) condition, the most possible decomposition pathway for methanthiol on Pt(111) is found as CH(3)SH --> CH(3)S --> CH(2)S --> CHS --> CH + S --> C + S, in which the C-S bond cleavage mainly occurs at the CHS species. However, the decomposition pathway is CH(3)SH --> CH(3)S --> CH(3) + S under the hydrogenation condition; the C-S bond scission mainly occurs at CH(3)S. The Bronsted-Evans Polanyi relation holds for each of the S-H, C-H, and C-S bond scission reactions. PMID- 20578755 TI - A direct probe of the interplay between bilayer morphology and surface reactivity in polymersomes. AB - Bilayer vesicles self-assembled from amphiphilic poly(ethylene oxide)-b polybutadiene (PEO-b-PBd) copolymers are cell-like structures whose high stability and tunable membrane properties make them ideal for use as potential drug carriers and cell mimicry templates. Understanding how the surface interactions (reaction, binding, etc.) are governed by the bilayer structure is critical to enable construction of polymersomes with tailored colloidal behavior. Here, we adapt a previously established chemical labeling method by incorporating coumarin functionalized copolymer into the vesicular structure. This allows us to probe the effect of poly(ethylene glycol) (PEG) brush and surface architecture on the bimolecular quenching reaction occurring at the polymersome surface. Using these measurements, we have tracked quenching in free solution, on bare particles, and on two types of vesicle surfaces: one where the functionalized copolymer groups are longer than the surrounding unfunctionalized copolymer, and one where both functionalized and unfunctionalized groups are the same length. We find that quenching in the presence of the PEG brush proceeds at less than half the free solution rate in both vesicle architectures. However, the quenching rate is further reduced when the functionalized and unfunctionalized groups are the same length. The surface reaction appears to be dominated by quencher diffusion, a conclusion supported by conductivity measurements and ion partition studies indicating that these effects arise as a consequence of retarded ion mobility in the presence of the PEG brush rather than ion exclusion effects. These studies reveal the interplay between the vesicle bilayer architecture (copolymer composition, chain length, local concentration surrounding the active site) and the surface reaction rate, thereby providing useful insights that can help guide the design of polymersomes with desired functional properties. PMID- 20578757 TI - Self-assembled structures and pKa value of oleic acid in systems of biological relevance. AB - In the human digestion process, triglycerides are hydrolyzed by lipases to monoglycerides and the corresponding fatty acids. Here we report the self assembly of structures in biologically relevant, emulsified oleic acid-monoolein mixtures at various pH values and oleic acid concentrations. Small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering were used to investigate the structures formed, and to follow their transitions while these factors were varied. The addition of oleic acid to monoolein-based cubosomes was found to increase the critical packing parameter in the system. Structural transitions from bicontinuous cubosomes through hexosomes and micellar cubosomes (Fd3m symmetry) to emulsified microemulsions occur with increasing oleic acid concentration. At sufficiently high oleic acid concentration, the internal particle structure was also found to strongly depend on the pH of the aqueous phase: transformations from emulsified microemulsion through micellar cubosomes, hexosomes, and bicontinuous cubosomes to vesicles can be observed as a function of increasing pH. The reversible transition from liquid crystals to vesicles occurs at intestinal pH values (between pH 7 and 8). The hydrodynamic radius of the particles decreases from around 120 nm for internally structured particles to around 60 nm for vesicles. All transitions with pH are reversible. Finally, the apparent pK(a) for oleic acid in monoolein could be determined from the change of structure with pH. This value is within the physiological pH range of the intestine and depends somewhat on composition. PMID- 20578756 TI - Carbon acid induced Mukaiyama aldol type reaction of sterically hindered ketones. AB - 1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane (Tf(2)CHCH(2)CHTf(2)) is one of the most effective Bronsted acid precatalysts for the Mukaiyama aldol type reactions of sterically hindered ketones. By using Tf(2)CHCH(2)CHTf(2) in a range from 0.5 to 2.0 mol %, the vinylogous Mukaiyama aldol reaction of alpha substituted cyclohexanones with 2-silyloxyfurans smoothly proceeded to give the aldol products in excellent yield without the loss of diastereoselectivity. Under similar conditions, acyclic ketene silyl acetals also performed as nice nucleophiles toward sterically hindered ketones. These findings suggest that Tf(2)CHCH(2)CHTf(2) induced Mukaiyama aldol type reactions can overcome the steric hindrance between reaction sites. PMID- 20578758 TI - Surfactant distribution in waterborne acrylic films. 1. Bulk investigation. AB - The distribution of an anionic surfactant, sodium dodecyl sulfate (SDS), in waterborne acrylic films was investigated, focusing on the effects of particle composition and size, and pH of the latex. The observed surfactant distributions could be classified in two categories: homogeneous and heterogeneous, the latter showing SDS aggregates. The shape of the profiles was related to the stability of the latex during drying, at short interparticular distances. The stability of the latex was determined by the presence or not of fixed charges at the surface of the particles. The latices with particles carrying neutralized acrylic acid at high pH (COO(-)) led to homogeneous distributions, whereas the latices with acrylic acid at low pH (COOH) or without acrylic acid led to heterogeneous distributions. Our interpretation is that the stable latices present a narrow network of paths between particles at high polymer volume fraction, limiting the mobility of the surfactant, whereas in the less stable latices wider routes between flocs allow enough mobility for large aggregate formation. Thermal treatments of the dry films confirmed the strong confinement of the surfactant in the dense film structure obtained at high pH and the more open structure, allowing easier surfactant transport and oxygen penetration, observed at low pH. In order to account for the shapes of the profiles more quantitatively, a model was developed based on the diffusion of the surfactant and its transport by the drying front. It was found that the apparent diffusion coefficient of SDS micelles had to be lowered to a great extent (D = 10(-13)-10(-14) m(2)/s) during drying in order to explain aggregate formation. It should be even lower (D = 10( 15) m(2)/s) to interpret homogeneous surfactant profiles. These results are consistent with our hypothesis of the key importance of the surfactant mobility during drying. PMID- 20578759 TI - Retraction. Pyrenebutyrate-mediated delivery of quantum dots across the plasma membrane of living cells. PMID- 20578760 TI - Probing valence orbital composition with iron Kbeta X-ray emission spectroscopy. AB - A systematic study of 12 ferric and ferrous Kbeta X-ray emission spectra (XES) is presented. The factors contributing to the Kbeta main line and the valence to core region of the spectra are experimentally assessed and quantitatively evaluated. While the Kbeta main line spectra are dominated by spin state contributions, the valence to core region is shown to have greater sensitivity to changes in the chemical environment. A density functional theory (DFT) based approach is used to calculate the experimental valence spectra and to evaluate the contributions to experimental intensities and energies. The spectra are found to be dominated by iron np to 1s electric dipole allowed transitions, with pronounced sensitivity to spin state, ligand identity, ligand ionization state, hybridization state, and metal-ligand bond lengths. These findings serve as an important calibration for future applications to iron active sites in biological and chemical catalysis. Potential applications to Compound II heme derivatives are highlighted. PMID- 20578761 TI - Proton transport through the influenza A M2 channel: three-dimensional reference interaction site model study. AB - The three-dimensional distribution function (DF) and the potential of mean force (PMF) of water and hydronium ions in five protonated states of the influenza A M2 channel are calculated by means of the three-dimensional reference interaction site model (3D-RISM) theory in order to clarify the proton conduction mechanism of the channel. Each protonated state, denoted as iH, where i = 0-4, has a different number of protonated histidines, from 0 to 4. The DF of water in each state exhibits closed structures of 0H, 1H, and 2H and open structures in 3H and 4H. In the closed form, the DF and PMF indicate that hydronium ions are excluded from the channel. In contrast, the ion can distribute throughout the opened channel. The barrier in PMF of 3H, approximately 3-5 kJ/mol, is lower than that of 4H, 5-7 kJ/mol, indicating that 3H has higher permeability to protons. On the basis of the radial DFs of water and hydronium ions around the imidazole rings of His37, we propose a new mechanism of proton transfer through the gating region of the channel. In this process, a hydronium ion hands a proton to a non-protonated histidine through a hydrogen bond between them, and then the other protonated histidine releases a proton to a water molecule via a hydrogen bond. The process transfers a proton effectively from one water molecule to another. PMID- 20578762 TI - Role of specific components from commercial inactive dry yeast winemaking preparations on the growth of wine lactic acid bacteria. AB - The role of specific components from inactive dry yeast preparations widely used in winemaking on the growth of three representative wine lactic acid bacteria (Oenococcus oeni, Lactobacillus hilgardii and Pediococcus pentosaceus) has been studied. A pressure liquid extraction technique using solvents of different polarity was employed to obtain extracts with different chemical composition from the inactive dry yeast preparations. Each of the extracts was assayed against the three lactic acid bacteria. Important differences in the effect of the extracts on the growth of the bacteria were observed, which depended on the solvent employed during the extraction, on the type of commercial preparations and on the lactic acid bacteria species. The extracts that exhibited the most different activity were chemically characterized in amino acids, free monosaccharides, monosaccharides from polysaccharides, fatty acids and volatile compounds. In general, specific amino acids and monosaccharides were related to a stimulating effect whereas fatty acid composition and likely some volatile compounds seemed to show an inhibitory effect on the growth of the lactic acid bacteria. These results may provide novel and useful information in trying to obtain better and more specific formulations of winemaking inactive dry yeast preparations. PMID- 20578763 TI - Hydroxyterphenylphoshine-palladium catalyst for benzo[b]furan synthesis from 2 chlorophenols. bifunctional ligand strategy for cross-coupling of chloroarenes. AB - A catalyst composed of Pd and hydroxyterphenylphosphine was found to be effective for one-pot benzo[b]furan synthesis from 2-chlorophenols and alkynes. PMID- 20578764 TI - Formation and fragmentation of quadruply charged molecular ions by intense femtosecond laser pulses. AB - We investigated the formation and fragmentation of multiply charged molecular ions of several aromatic molecules by intense nonresonant femtosecond laser pulses of 1.4 mum with a 130 fs pulse duration (up to 2 x 10(14) W cm(-2)). Quadruply charged states were produced for 2,3-benzofluorene and triphenylene molecular ion in large abundance, whereas naphthalene and 1,1'-binaphthyl resulted only in up to triply charged molecular ions. The laser wavelength was nonresonant with regard to the electronic transitions of the neutral molecules, and the degree of fragmentation was strongly correlated with the absorption of the singly charged cation radical. Little fragmentation was observed for naphthalene (off-resonant with cation), whereas heavy fragmentation was observed in the case of 1,1'-binaphthyl (resonant with cation). The degree of H(2) (2H) and 2H(2) (4H) elimination from molecular ions increased as the charge states increased in all the molecules examined. A striking difference was found between triply and quadruply charged 2,3-benzofluorene: significant suppression of molecular ions with loss of odd number of hydrogen was observed in the quadruply charged ions. The Coulomb explosion of protons in the quadruply charged state and succeeding fragmentation resulted in the formation of triply charged molecular ions with an odd number of hydrogens. The hydrogen elimination mechanism in the highly charged state is discussed. PMID- 20578765 TI - ENDOR study on the dynamic properties of the first stable paramagnetic center in gamma-irradiated L-alanine crystals. AB - Dynamic properties of the first stable l-alanine radical, SAR1, induced by gamma irradiation of l-alanine crystals, have been investigated by the electron nuclear double resonance technique (ENDOR). The study focuses on the dynamic properties of the alpha-proton hyperfine splitting in the temperature range from 180 to 320 K. In this region the motion of the NH(3)(+) and CH(3) groups exhibits slow and fast motional dynamics in comparison to the nuclear and electron Larmor frequencies, respectively. Evidence for different conformations of the SAR1 center is presented on the basis of thermodynamic properties of the alpha hyperfine splitting. The activation processes causing the broadening of the ENDOR lines are studied. At room temperature the motional dynamics of the SAR1 center are modulated by the dynamics of the charged, neighboring NH(3)(+) group. PMID- 20578766 TI - Reexamination of the quenching of NO(+) vibrations by O(2)(a (1)Delta(g)). AB - The quenching of vibrationally excited NO(+) by O(2)(a (1)Delta(g)) has been examined using the monitor ion technique and chemical generation of O(2)(a (1)Delta(g)). In contrast to previous results which showed that the rate constant was much larger than for ground state O(2), this study finds that the rate constant for quenching is below the detection limit (<10(-11) cm(3) s(-1)) of this experiment. The previous experiments produced O(2)(a (1)Delta(g)) in a discharge, which would also produces O atoms. We found that the monitor ion CH(3)I(+) reacts with O atoms to produce CHIOH(+). This is the likely cause of error in the previous experiments. PMID- 20578767 TI - The aromatic 8-electron cubic silicon clusters Be@Si(8), B@Si(8)(+), and C@Si(8)(2+). AB - The geometrical and electronic structures of the Si(8)(2-) dianion and isovalent silicon clusters doped by main second-row elements including Li@Si(8)(-), Be@Si(8), B@Si(8)(+), C@Si(8)(2+), N@Si(8)(3+), and O@Si(8)(4+), are investigated using quantum chemical methods. The analyses of phenomenological shell model (PSM) combined with partial electron localizability indicators (pELI-D) rationalize the existence of cubic silicon clusters. A cubic cluster can be formed, in the cases of Be@Si(8), B@Si(8)(+), and C@Si(8)(2+), when three conditions are satisfied, namely, a full occupancy of electronic shells (34 electrons), a presence of positive charge at the center, and a type of spherical aromaticity. A chemical bonding picture for the cubic cage of the doped silicon clusters is illustrated. Each Si atom has four lobes of sp(3) hybridization in which three lobes make three covalent sigma bonds with other Si atoms, and the fourth lobe makes a chemical bond with the dopant. The eight delocalized electrons distributed on the fourth lobes describing the bonding between dopant and Si cage follow the Hirsch rule. We demonstrate that a way of applying electron counting rule is to take into account delocalized electrons on the shell orbitals with N > 1 (2S and 2P shell orbitals). PMID- 20578768 TI - Calculated spectroscopy and atmospheric photodissociation of phosphoric acid. AB - Detection of phosphine (PH(3)) gas in the upper troposphere suggests that the biogeochemical P cycle also includes an atmospheric component that consists of volatile phosphorus-containing molecules. A reasonable end product for the oxidation of PH(3) in the atmosphere is phosphoric acid (H(3)PO(4)). We propose that H(3)PO(4) may be photodissociated into HOPO(2) and H(2)O in the stratosphere, where H(3)PO(4) is likely to be present in gaseous form. We have calculated the energy barrier of this reaction and show that in addition to electronic transitions, OH-stretching overtone transitions can also provide the necessary energy. OH-stretching fundamental and overtone transitions were calculated with the use of an anharmonic oscillator local mode model. The probability of overtone induced photodissociation was estimated with molecular dynamical reaction coordinate simulations. Electronic transitions were calculated with the equation of motion coupled cluster singles doubles method. We have calculated the photodissociation rate constants for absorption of visible, UV, and Lyman-alpha radiation at altitudes from 20 to 100 km. We show that at altitudes between 30 and 70 km, the photodissociation of H(3)PO(4) is likely to proceed via absorption in the UV region by electronic transitions. PMID- 20578769 TI - Ferroelectric hydration shells around proteins: electrostatics of the protein water interface. AB - Numerical simulations of hydrated proteins show that protein hydration shells are polarized into a ferroelectric layer with large values of the average dipole moment magnitude and the dipole moment variance. The emergence of the new polarized mesophase dramatically alters the statistics of electrostatic fluctuations at the protein-water interface. The linear response relation between the average electrostatic potential and its variance breaks down, with the breadth of the electrostatic fluctuations far exceeding the expectations of the linear response theories. The dynamics of these non-Gaussian electrostatic fluctuations are dominated by a slow (approximately = 1 ns) component that freezes in at the temperature of the dynamical transition of proteins. The ferroelectric shell propagates 3-5 water diameters into the bulk. PMID- 20578770 TI - Mutual interplay of light harvesting and triplet sensitizing in a perylene bisimide antenna-fullerene dyad. AB - A flexible organic dyad consisting of a perylene bisimide antenna covalently linked to a [60]fullerene has been synthesized and studied by electrochemistry, steady-state spectroscopy, and time-resolved spectroscopy. We found that the energy absorbed by the perylene bisimide is transferred to the fullerene with an efficiency close to 100%. The fullerene in turn undergoes intersystem crossing followed by triplet energy transfer back to the perylene bisimide with an efficiency of at least 20%. Hence the perylene bisimide unit acts as an antenna for the fullerene, i.e., effectively extending the fullerene absorption far into the visible spectral range, while at the same time the fullerene acts as a triplet sensitizer for the perylene bisimide. This has severe consequences for the exploitation of the dye antenna-fullerene concept for light harvesting in solar cells. PMID- 20578771 TI - Nonhumidified intermediate temperature fuel cells using protic ionic liquids. AB - In this paper, the characterization of a protic ionic liquid, diethylmethylammonium trifluoromethanesulfonate ([dema][TfO]), as a proton conductor for a fuel cell and the fabrication of a membrane-type fuel cell system using [dema][TfO] under nonhumidified conditions at intermediate temperatures are described in detail. In terms of physicochemical and electrochemical properties, [dema][TfO] exhibits high activity for fuel cell electrode reactions (i.e., the hydrogen oxidation reaction (HOR) and oxygen reduction reaction (ORR)) at a Pt electrode, and the open circuit voltage (OCV) of a liquid fuel cell is 1.03 V at 150 degrees C, as has reported in ref 27. However, diethylmethylammonium bis(trifluoromethane sulfonyl)amide ([dema][NTf(2)]) has relatively low HOR and ORR activity, and thus, the OCV is ca. 0.7 V, although [dema][NTf(2)] and [dema][TfO] have an identical cation ([dema]) and similar thermal and bulk transport properties. Proton conduction occurs mainly via the vehicle mechanism in [dema][TfO] and the proton transference number (t(+)) is 0.5-0.6. This relatively low t(+) appears to be more disadvantageous for a proton conductor than for other electrolytes such as hydrated sulfonated polymer electrolyte membranes (t(+) = 1.0). However, fast proton-exchange reactions occur between ammonium cations and amines in a model compound. This indicates that the proton exchange mechanism contributes to the fuel cell system under operation, where deprotonated amines are continuously generated by the cathodic reaction, and that polarization of the cell is avoided. Six-membered sulfonated polyimides in the diethylmethylammonium form exhibit excellent compatibility with [dema][TfO]. The composite membranes can be obtained up to a [dema][TfO] content of 80 wt % and exhibit good thermal stability, high ionic conductivity, and mechanical strength and gas permeation comparable to those of hydrated Nafion. H(2)/O(2) fuel cells prepared using the composite membranes can successfully operate at temperatures from 30 to 140 degrees C under nonhumidified conditions, and a current density of 250 mA cm(-2) is achieved at 120 degrees C. The protic ionic liquid and its composite membrane are a possible candidate for an electrolyte of a H(2)/O(2) fuel cell that operates under nonhumidified conditions. PMID- 20578772 TI - Evolution of various porphyrin nanostructures via an oil/aqueous medium: controlled self-assembly, further organization, and supramolecular chirality. AB - We have shown that various porphyrin-containing nanostructures can be easily synthesized by a surfactant-assisted self-assembly (SAS) method, where an oil/aqueous medium is employed. When a chloroform solution of zinc 5,10,15,20 tetra(4-pyridyl)-21H,23H-porphine (ZnTPyP) was added dropwise into cetyltrimethylammonium bromide (CTAB) aqueous solution, diverse ZnTPyP-based nanostructures, including hollow nanospheres, solid nanospheres, nanotubes, nanorods, and nanofibers, were successfully assembled. Depending on the aging time, when a low-concentration CTAB aqueous solution was employed, hollow nanospheres or nanotubes were produced. In contrast, either solid nanospheres or nanorods were obtained by using a CTAB aqueous solution in moderate concentration. Moreover, solid nanospheres or nanofibers were produced, when a high-concentration CTAB aqueous solution was used. We have further shown that the nanorods can be hierarchically organized into a regular nanoarray on silicon substrates over a large area, while the other nanostructures cannot. Interestingly, the nanorods displayed distinct supramolecular chirality although the employed ZnTPyP is achiral. On the basis of the information obtained from scanning electron microscopy, high-resolution transmission electron microscopy, fast Fourier transformation, energy-dispersive X-ray spectroscopy, X-ray diffraction, and UV-vis and circular dichroism spectra, a tentative explanation has been proposed. Our investigation suggests that the SAS method via an oil/aqueous medium is an efficient way to synthesize organic nanostructures in a controlled manner, and that such nanostructures can show different chiroptical and assembly properties. PMID- 20578773 TI - Anomeric effects in sulfonyl compounds: an experimental and computational study of fluorosulfonyl azide, FSO(2)N(3), and trifluoromethylsulfonyl azide, CF(3)SO(2)N(3). AB - Fluorosulfonyl azide, FSO(2)N(3), was characterized by IR (gas phase, Ar matrix), and Raman (liquid) spectroscopy. According to the matrix IR spectrum of (18)O labeled FSO(2)N(3), its two oxygen atoms are nonequivalent. This assumption was confirmed by the X-ray crystal structure of FSO(2)N(3) at -123 degrees C, as only one conformer was observed with one of the S=O bonds in synperiplanar position to the N(3) group (phi(OS-NN) = -14.8(3) degrees) with respect to the S-N bond. The same conformation was found for trifluoromethylsulfonyl azide, CF(3)SO(2)N(3) (phi(OS-NN) = -23.74(15) degrees), in the solid state. The preference of such a synperiplanar configuration between S=O and N(3) was rationalized by a predominant anomeric interaction of n(sigma)(N) --> sigma*(S-O), as supported by the experiment and quantum chemical calculations. PMID- 20578774 TI - Elucidating the association of water in wet 1-octanol from normal to high temperature by near- and mid-infrared spectroscopy. AB - Near- (NIR) and mid-infrared (MIR) absorption spectra of pure and water-saturated 1-octanol were measured along the liquid-gas coexistence curve from ambient temperature and pressure up to 300 degrees C and 10 MPa. Density of the mixture as a function of temperature was assessed by spectral analysis in the NIR region. Two distinct regimes of temperature were identified in the evolution of solvent subtracted spectra: at normal conditions and up to 180 degrees C, water is organized in multimeric H-bonded aggregates, while at higher temperature, mainly dimers and monomers exist. Water-water and alcohol-alcohol H-bonding interactions play a major role in wet octanol at low temperature, with resulting microheterogeneity and water segregation at a molecular level; on the other hand, water-alcohol interactions are relevant at higher temperature, as also revealed by the estimated density. At low temperature, water dissolved in octanol shows features which are comparable to those of interfacial water obtained by vibrational sum frequency (VSF) spectroscopy, while at high temperature the spectra generally reproduce those of water in the supercritical phase. Overall spectral assignment was supported by ab initio calculations at the MP2 level on small water clusters. PMID- 20578775 TI - Side chain and flexibility contributions to the Raman optical activity spectra of a model cyclic hexapeptide. AB - A model peptide, cyclo-(Phe-d-Pro-Gly-Arg-Gly-Asp), with a distinct folded structure containing short beta-hairpin and beta-sheet patterns was studied by Raman and Raman optical activity (ROA) spectroscopies. Unlike for previously analyzed vibrational circular dichroism of the same compound (Chirality 2008, 20, 1104), the Raman spectrum is dominated by side chain contributions and is more sensitive to their geometry fluctuations. The spectra and molecular motion were analyzed with the aid of the density functional theory simulations combined with molecular dynamics (MD). The side chain geometry fluctuations were found to significantly contribute to the broadening of the spectral bands, while dynamics of the backbone is rather restricted. According to our MD results, the side chains do not move freely but largely oscillate around preferred conformations. Averaging of computed spectra for many structures derived from the MD trajectories provided better spectral profiles than did a fixed geometry. The Raman and ROA scattering is dominated by the more polarizable phenylalanine and proline groups, as could be verified both by the computations and by comparison to experiments with a model Phe-d-Pro dipeptide. Computational analyses suggest that the ROA spectrum mostly senses local side chain conformation, whereas a vibrational coupling between different side chains contributes less. The coupling is mostly mediated by the peptide backbone and is restricted to specific vibrational region. The ROA spectroscopic technique thus provides important local structural information that needs, however, to be extracted by multiscale (QM/MM) simulation techniques. PMID- 20578776 TI - Multidentate poly(ethylene glycol) ligands provide colloidal stability to semiconductor and metallic nanocrystals in extreme conditions. AB - We present the design and synthesis of a new set of poly(ethylene glycol) (PEG) based ligands appended with multidentate anchoring groups and test their ability to provide colloidal stability to semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs) in extreme buffer conditions. The ligands are made of a PEG segment appended with two thioctic acid (TA) or two dihydrolipoic acid (DHLA) anchoring groups, bis(TA)-PEG-OCH(3) or bis(DHLA)-PEG-OCH(3). The synthesis utilizes Michael addition to create a branch point at the end of a PEG chain combined with carbodiimide-coupling to attach two TA groups per PEG chain. Dispersions of CdSe-ZnS core-shell QDs and AuNPs with remarkable long-term colloidal stability at pHs ranging from 1.1 to 13.9 and in the presence of 2 M NaCl have been prepared and tested using these ligands. AuNPs with strong resistance to competition from dithiothreitol (as high as 1.5 M) have also been prepared. This opens up possibilities for using them as stable probes in a variety of bio-related studies where resistance to degradation at extreme pHs, at high electrolyte concentration, and in thiol-rich environments is highly desirable. The improved colloidal stability of nanocrystals afforded by the tetradentate ligands was further demonstrated via the assembly of stable QD nuclear localization signal peptide bioconjugates that promoted intracellular uptake. PMID- 20578778 TI - The effect of protest zeros on estimates of willingness to pay in healthcare contingent valuation analysis. AB - 'Protest zeros' occur when respondents reject some aspect of the contingent valuation (CV) market scenario by reporting a zero value even though they place a positive value on the amenity being valued. This is inevitable even in the best designed CV study, and, when excluded on an ad hoc basis, may cause a selection bias problem. This could affect the reliability of the willingness to pay (WTP) estimates obtained for preference assessment. Treatment of 'protest zeros' in general, and particularly in the context of developing countries, has been rather unsatisfactory. Most case studies employ the Heckman 2-step approach, which is much less robust to co-linearity problems than the Full Information Maximum Likelihood (FIML) estimator. The main objective of this article is to illustrate a sequential procedure to simultaneously deal with co-linearity and selectivity bias resulting from excluding 'protest zeros' in CV analysis. The sequential procedure involves different levels of estimation and diagnostics with the 2-step and FIML estimators; the duration of the procedure depends on the diagnostic test results at each stage of the estimations. The data used for the analysis were elicited using the conventional dichotomous choice buttressed with an open-ended follow-up question. The survey was designed to elicit households' WTP for a proposed community-based malaria control scheme in rural Cameroon. In the application context, we found that the different levels of estimation and diagnostics resulted in reliable WTP estimates from the FIML approach, which would obviously have been overlooked in the absence of such diagnostics. PMID- 20578777 TI - Oncologist preferences for health states associated with the treatment of advanced ovarian cancer. AB - BACKGROUND: For advanced epithelial ovarian cancer, oncologists are faced with multiple treatment options that differ in terms of possible clinical and patient reported outcomes. OBJECTIVE: To explore oncologists' preferences for hypothetical outcome scenarios (i.e. health states) resulting from various treatment options. METHODS: Six hypothetical health states reflecting varying levels of toxicity, treatment efficacy and emotional well-being were developed representing advanced ovarian cancer treatment. During face-to-face interviews, oncologists provided their relative preferences for these health states using a visual analogue scale and Standard Gamble exercise. RESULTS: The 34 participating oncologists consistently preferred health states reflecting high treatment efficacy over low efficacy for patients with newly diagnosed disease, regardless of toxicity or emotional well-being. In the setting of recurrent disease, physicians preferred a heath state only if it reflected both high efficacy and positive emotional well-being. CONCLUSIONS: These data suggest that oncologists may choose treatments that maximize clinical efficacy only when not associated with severe toxicities or low emotional well-being unless associated with a large improvement in efficacy. Physicians may prefer a more toxic chemotherapy regimen that improves survival, and are more willing to compromise emotional well-being for a large survival advantage in the setting of newly diagnosed disease. Slight improvements in clinical efficacy may not be acceptable to oncologists unless associated with higher emotional well-being for the patient. PMID- 20578779 TI - Audit of Diabetes-Dependent Quality of Life (ADDQoL) [Chinese Version for Singapore] questionnaire: reliability and validity among Singaporeans with type 2 diabetes mellitus. AB - BACKGROUND: The Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire is an individualized instrument that measures the impact of diabetes mellitus on quality of life (QOL). With the worldwide increase in the number of Chinese people diagnosed with diabetes, we anticipated that a Chinese language version of the ADDQoL would be urgently needed. OBJECTIVE: To evaluate the reliability and validity of the ADDQoL (Chinese version for Singapore) among Chinese-speaking Singaporeans with type 2 diabetes mellitus (T2DM). METHODS: Chinese versions of the ADDQoL, EuroQoL-Visual Analogue Scale (EQ-VAS), EQ-5D and SF-6D were administered to Chinese-speaking participants with T2DM (aged > or =21 years) at a tertiary acute-care hospital by convenience sampling. The ADDQoL was assessed for the following: internal consistency (Cronbach's alpha); test-retest reliability (intraclass correlation coefficient [ICC]); factor structure; known groups validity (insulin requiring vs non-insulin requiring, with vs without diabetes-related complications, overweight/obese vs not overweight/obese); and convergent and divergent validity (with EQ-VAS, EQ-5D and SF-6D). The usefulness of weighting and 'not applicable' (NA) options (key features of ADDQoL) were also evaluated. RESULTS: In 88 participants (58% male, mean [SD] age 56.6 [11.74] years), the mean (SD) ADDQoL average weighted impact (AWI) score was -2.613 (1.899). Cronbach's alpha was 0.941 and the ICC was 0.955 (95% CI 0.812, 0.990). In confirmatory factor analysis, the hypothesized one-factor solution was supported. ADDQoL AWI scores correlated strongly with ADDQoL diabetes-dependent global QOL scores (Spearman's rank correlation coefficient [r(s)] = 0.5983) and weakly with generic measures (r(s) = -0.028 for ADDQoL present global QOL scores, 0.310 for EQ-VAS, 0.164 for EQ-5D and 0.281 for SF-6D). Participants who required insulin, those with diabetes-related complications and those who were overweight/obese reported lower AWI scores, but the differences were not statistically significant. Importance scores of zero were assigned 1-28% of the time and the NA options were selected 3-49% of the time. CONCLUSIONS: The ADDQoL is reliable and probably valid for assessing QOL among Chinese-speaking Singaporeans with T2DM, although known-groups validity warrants further investigation. PMID- 20578780 TI - Costs and consequences of clopidogrel versus aspirin for secondary prevention of ischaemic events in (high-risk) atherosclerotic patients in Sweden: a lifetime model based on the CAPRIE trial and high-risk CAPRIE subpopulations. AB - BACKGROUND: Antiplatelet therapy plays a central role in the prevention of atherothrombotic events. Both acetylsalicylic acid (aspirin) and clopidogrel have been shown to reduce the risk of recurrent cardiovascular events in various subgroups of patients with vascular disease. OBJECTIVE: To estimate the cost effectiveness of clopidogrel versus aspirin in Sweden for the prevention of atherothrombotic events based on CAPRIE trial data. The focus of this study is on two high-risk subpopulations: (i) patients with pre-existing symptomatic atherosclerotic disease; and (ii) patients with polyvascular disease. METHODS: A Markov model combining clinical, epidemiological and cost data was used to assess the economic value of clopidogrel compared with aspirin during a patient's lifetime. A societal perspective was used, with costs stated in Swedish kronor (SEK), year 2007 values. For the first 2 years, the clinical input for the model was based on the relevant subpopulations in the CAPRIE trial. Thereafter, transition probabilities were extrapolated, taking account of increased risks related to age and to a history of events. Cost effectiveness of 2 years of therapy is presented as cost per life-year gained (LYG) and as cost per QALY. Univariate and multivariate sensitivity analyses were performed to investigate robustness of results. RESULTS: For patients resembling the total CAPRIE population, who were treated with clopidogrel, the expected cost per LYG was SEK217,806 and the cost per QALY was estimated at SEK169,154. For the high-risk CAPRIE subpopulations, costs per QALY were lowest for patients with pre-existing symptomatic atherosclerotic disease (SEK38,153). Using a 'willingness-to-pay' perspective indicated that treatment with clopidogrel instead of aspirin in high risk patients is associated with a high probability for cost effectiveness; 81% using a threshold of SEK100,000 per QALY and 98% using a threshold of SEK500,000 per QALY. Overall, the results appeared to be robust over the sensitivity analyses performed. CONCLUSION: When considering the cost-effectiveness categorization as proposed by the Swedish National Board of Health and Welfare, clopidogrel appears to be associated with costs per QALY that range from intermediate in the total CAPRIE population to low in high-risk atherosclerotic patients. PMID- 20578782 TI - Impact dynamics in biped locomotion analysis: two modelling and implementation approaches. AB - Stability during the biped locomotion and especially humanoid robots walking is a big challenge in robotics modelling. This paper compares the classical and novel methodologies of modelling and algorithmic implementation of the impact/contact dynamics that occurs during a biped motion. Thus, after establishing the free biped locomotion system model, a formulation using variational inequalities theory via a Linear Complementarity Problem then an impedance model are explicitly developed. Results of the numerical simulations are compared to the experimental measurements then the both approaches are discussed. PMID- 20578781 TI - Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada. AB - BACKGROUND: Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. OBJECTIVE: To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. METHODS: Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). RESULTS: Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin glargine plus OADs showed a very slight increase in total direct costs ($Can 343 +/- 2572), resulting in ICERs of $Can 6750 per life-year gained (LYG) and $Can 7923 per QALY gained. However, considerable uncertainty around the ICERs was demonstrated by insulin glargine having a 50% probability of being cost effective at a willingness-to-pay threshold of $Can 10,000 per QALY, and a 54% probability at a $Can 20,000 threshold. Base-case results were most sensitive to assumed disutilities for hypoglycaemic events, to the assumed effect of insulin glargine plus OADs on HbA(1c), and to its assumed acquisition costs. CONCLUSIONS: These findings should be interpreted within the context of a large degree of uncertainty and of several study limitations that include a single clinical trial as the source for primary treatment assumptions and a single province as the source for most cost inputs. Under current study assumptions and limitations, insulin glargine plus OADs was projected to be a cost-effective option, compared with premixed insulin only, for the treatment of insulin-naive patients with type 2 diabetes unresponsive to OADs. Additional work is needed to examine the generalizability of the findings to individual jurisdictions of the Canadian healthcare system. PMID- 20578783 TI - A method for analyzing the stability of the resting state for a model of pacemaker cells surrounded by stable cells. AB - The purpose of this paper is to derive and analyze methods for examining the stability of solutions of partial differential equations modeling collections of excitable cells. In particular, we derive methods for estimating the principal eigenvalue of a linearized version of the Luo-Rudy I model close to an equilibrium solution. It has been suggested that the stability of a collection of unstable cells surrounded by a large collection of stable cells can be studied by considering only a collection of unstable cells equipped with a Dirichlet type boundary condition. This method has earlier been applied to analytically assess the stability of a reduced version the Luo-Rudy I model. In this paper we analyze the accuracy of this technique and apply it to the full Luo-Rudy I model. Furthermore, we extend the method to provide analytical results for the FitzHugh Nagumo model in the case where a collection of unstable cells is surrounded by a collection of stable cells. All our analytical findings are complemented by numerical computations computing the principal eigenvalue of a discrete version of linearized models. PMID- 20578784 TI - Rotating antibiotics selects optimally against antibiotic resistance, in theory. AB - The purpose of this paper is to use mathematical models to investigate the claim made in the medical literature over a decade ago that the routine rotation of antibiotics in an intensive care unit (ICU) will select against the evolution and spread of antibiotic-resistant pathogens. In contrast, previous theoretical studies addressing this question have demonstrated that routinely changing the drug of choice for a given pathogenic infection may in fact lead to a greater incidence of drug resistance in comparison to the random deployment of different drugs. Using mathematical models that do not explicitly incorporate the spatial dynamics of pathogen transmission within the ICU or hospital and assuming the antibiotics are from distinct functional groups, we use a control theoretic approach to prove that one can relax the medical notion of what constitutes an antibiotic rotation and so obtain protocols that are arbitrarily close to the optimum. Finally, we show that theoretical feedback control measures that rotate between different antibiotics motivated directly by the outcome of clinical studies can be deployed to good effect to reduce the prevalence of antibiotic resistance below what can be achieved with random antibiotic use. PMID- 20578785 TI - Theoretical models for chronotherapy: periodic perturbations in hyperchaos. AB - In this work, a hyperchaotic system was used as a model for chronotherapy. We applied a periodic perturbation to a variable, varying the period and amplitude of forcing. The system, five-dimensional, has until three positive Lyapunov exponents. As a result, we get small periodical windows, but it was possible to get large areas of hyperchaos of two positive Lyapunov exponents from a chaotic behavior. In this chronotherapy model, chaos could be considered as a dynamical disease, and therapy goal must be to restore the hyperchaotic state. PMID- 20578786 TI - Rational exemption to vaccination for non-fatal SIS diseases: globally stable and oscillatory endemicity. AB - 'Rational' exemption to vaccination is due to a pseudo-rational comparison between the low risk of infection, and the perceived risk of side effects from the vaccine. Here we consider rational exemption in an SI model with information dependent vaccination where individuals use information on the disease's spread as their information set. Using suitable assumptions, we show the dynamic implications of the interaction between rational exemption, current and delayed information. In particular, if vaccination decisions are based on delayed informations, we illustrate both global attractivity to an endemic state, and the onset, through Hopf bifurcations, of general Yakubovich oscillations. Moreover, in some relevant cases, we plot the Hopf bifurcation curves and we give a behavioural interpretation of their meaning. PMID- 20578787 TI - On the interaction between the immune system and an exponentially replicating pathogen. AB - In this work, we generalize the Pugliese-Gandolfi Model [A. Pugliese and A. Gandolfi, Math Biosc, 214,73 (2008)] of interaction between an exponentially replicating pathogen and the immune system. After the generalization, we study the properties of boundedness and unboundedness of the solutions, and we also give a condition for the global eradication as well as for the onset of sustained oscillations. Then, we study the condition for the uniqueness of the arising limit cycle, with numerical applications to the Pugliese-Gandolfi model. By means of simulations, we also show some alternative ways to reaching the elimination of the pathogen and interesting effects linked to variations in aspecific immune response. After shortly studying some pathological cases of interest, we include in our model distributed and constant delays and we show that also delays may unstabilize the equilibria. PMID- 20578788 TI - Mechanisms for stable coexistence in an insect community. AB - In this paper, we formulate a three-species ecological community model consisting of two aphid species (Acyrthosiphon pisum and Megoura viciae) and a specialist parasitoid (Aphidius ervi) that attacks only one of the aphids (A pisum). The model incorporates both density-mediated and trait-mediated host-parasitoid interactions. Our analysis shows that the model possesses much richer and more realistic dynamics than earlier models. Our theoretical results reveal a new mechanism for stable coexistence in a three-species community in which any two species alone do not co-exist. More specifically, it is known that, when a predator is introduced into a community of two competing species, if the predator only predates on the strong competitor, it can allow the weak competitor to survive, but may drive the strong competitor to extinction through over exploitation. We show that if the weak competitor interferes the predation on the strong competitor through trait-mediated indirect effects, then all three species can stably co-exist. PMID- 20578789 TI - Local stabilization and network synchronization: the case of stationary regimes. AB - Relationships between local stability and synchronization in networks of identical dynamical systems are established through the Master Stability Function approach. First, it is shown that stable equilibria of the local dynamics correspond to stable stationary synchronous regimes of the entire network if the coupling among the systems is sufficiently weak or balanced (in other words, stationary synchronous regimes can be unstable only if the coupling is sufficiently large and unbalanced). Then, it is shown that [de]stabilizing factors at local scale are [de]synchronizing at global scale again if the coupling is sufficiently weak or balanced. These results allow one to transfer, with almost no effort, what is known for simple prototypical models in biology and engineering to complex networks composed of these models. This is shown through a series of applications ranging from networks of electrical circuits to various problems in ecology and sociology involving migrations of plants, animal and human populations. PMID- 20578790 TI - A mathematical study of a syntrophic relationship of a model of anaerobic digestion process. AB - A mathematical model involving the syntrophic relationship of two major populations of bacteria (acetogens and methanogens), each responsible for a stage of the methane fermentation process is proposed. A detailed qualitative analysis is carried out. The local and global stability analyses of the equilibria are performed. We demonstrate, under general assumptions of monotonicity, relevant from an applied point of view, the global asymptotic stability of a positive equilibrium point which corresponds to the coexistence of acetogenic and methanogenic bacteria. PMID- 20578791 TI - Alternative transmission modes for Trypanosoma cruzi. AB - The parasite Trypanosoma cruzi, which causes Chagas' disease, is typically transmitted through a cycle in which vectors become infected through bloodmeals on infected hosts and then infect other hosts through defecation at the sites of subsequent feedings. The vectors native to the southeastern United States, however, are inefficient at transmitting T. cruzi in this way, which suggests that alternative transmission modes may be responsible for maintaining the established sylvatic infection cycle. Vertical and oral transmission of sylvatic hosts, as well as differential behavior of infected vectors, have been observed anecdotally. This study develops a model which accounts for these alternative modes of transmission, and applies it to transmission between raccoons and the vector Triatoma sanguisuga. Analysis of the system of nonlinear differential equations focuses on endemic prevalence levels and on the infection's basic reproductive number, whose form may account for how a combination of traditionally secondary infection routes can maintain the transmission cycle when the usual primary route becomes ineffective. PMID- 20578792 TI - Global stability of an HIV-1 model with distributed intracellular delays and a combination therapy. AB - Global stability is analyzed for a general mathematical model of HIV-1 pathogenesis proposed by Nelson and Perelson [11]. The general model include two distributed intracellular delays and a combination therapy with a reverse transcriptase inhibitor and a protease inhibitor. It is shown that the model exhibits a threshold dynamics: if the basic reproduction number is less than or equal to one, then the HIV-1 infection is cleared from the T-cell population; whereas if the basic reproduction number is larger than one, then the HIV-1 infection persists and the viral concentration maintains at a constant level. PMID- 20578793 TI - A cost-based comparison of quarantine strategies for new emerging diseases. AB - A classical epidemiological framework is used to provide a preliminary cost analysis of the effects of quarantine and isolation on the dynamics of infectious diseases for which no treatment or immediate diagnosis tools are available. Within this framework we consider the cost incurred from the implementation of three types of dynamic control strategies. Taking the context of the 2003 SARS outbreak in Hong Kong as an example, we use a simple cost function to compare the total cost of each mixed (quarantine and isolation) control strategy from a public health resource allocation perspective. The goal is to extend existing epi economics methodology by developing a theoretical framework of dynamic quarantine strategies aimed at emerging diseases, by drawing upon the large body of literature on the dynamics of infectious diseases. We find that the total cost decreases with increases in the quarantine rates past a critical value, regardless of the resource allocation strategy. In the case of a manageable outbreak resources must be used early to achieve the best results whereas in case of an unmanageable outbreak, a constant-effort strategy seems the best among our limited plausible sets. PMID- 20578794 TI - A model for phenotype change in a stochastic framework. AB - In some species, an inducible secondary phenotype will develop some time after the environmental change that evokes it. Nishimura (2006) [4] showed how an individual organism should optimize the time it takes to respond to an environmental change ("waiting time''). If the optimal waiting time is considered to act over the population, there are implications for the expected value of the mean fitness in that population. A stochastic predator-prey model is proposed in which the prey have a fixed initial energy budget. Fitness is the product of survival probability and the energy remaining for non-defensive purposes. The model is placed in the stochastic domain by assuming that the waiting time in the population is a normally distributed random variable because of biological variance inherent in mounting the response. It is found that the value of the mean waiting time that maximises fitness depends linearly on the variance of the waiting time. PMID- 20578795 TI - Redox signaling in human pathogens. AB - In recent studies of human bacterial pathogens, oxidation sensing and regulation have been shown to impact very diverse pathways that extend beyond inducing antioxidant genes in the bacteria. In fact, some redox-sensitive regulatory proteins act as major regulators of bacteria's adaptability to oxidative stress, an ability that originates from immune host response as well as antibiotic stress. Such proteins play particularly important roles in pathogenic bacteria S. aureus, P. aeruginosa, and M. tuberculosis in part because reactive oxygen species and reactive nitrogen species present significant challenges for pathogens during infection. Herein, we review recent progress toward the identification and understanding of oxidation sensing and regulation in human pathogens. The newly identified redox switches in pathogens are a focus of this review. We will cover several reactive oxygen species-sensing global regulators in both gram-positive and gram-negative pathogenic bacteria in detail. The following discussion of the mechanisms that these proteins employ to sense redox signals through covalent modification of redox active amino acid residues or associated metalloprotein centers will provide further understanding of bacteria pathogenesis, antibiotic resistance, and host-pathogen interaction. PMID- 20578796 TI - Silymarin: a novel antioxidant with antiglycation and antiinflammatory properties in vitro and in vivo. AB - The current study was designed to evaluate the effects of silymarin (SM) on advanced glycation endproduct (AGE) formation and monocyte activation induced by S100b, a specific ligand of receptor for AGEs. The in vivo verification of antiglycation, antioxidant, and antiinflammatory capacities was examined by 12 weeks of SM administration in streptozotocin-diabetic rats. In vitro glycation assays demonstrated that SM exerted marked inhibition during the late stages of glycation and subsequent crosslinking. Dual action mechanisms, namely, antioxidant and reactive carbonyl trapping activities, may contribute to its antiglycation effect. SM produced a significant decrease in monocytic interleukin 1beta and COX-2 levels and prevented oxidant formation caused by S100b, which appeared to be mediated by inhibition of p47phox membrane translocation. Chromatin immunoprecipitation demonstrated that S100b increased the recruitment of nuclear factor-kappaB transcription factor as well as cAMP response element binding-binding protein and coactivator-associated arginine methyltransferase-1 cofactors to the interleukin-1beta promoter, whereas these changes were inhibited with SM treatment. In vivo, SM reduced tissue AGE accumulation, tail collagen crosslinking, and concentrations of plasma glycated albumin. Levels of oxidative and inflammatory biomarkers were also significantly decreased in SM-treated groups compared with the diabetic group. These data suggest that SM supplementation may reduce the burden of AGEs in diabetics and may prevent resulting complications. PMID- 20578797 TI - Antioxidants and public health. PMID- 20578798 TI - Saccular aneurysm with basal rupture angiographically depicted as an aneurysm with stalk-like narrow neck. AB - On occasion, the wall of the aneurysm base can be the rupture site of the lesion, which poses a unique challenge for treatment. Although there has already been a report of the angiographic depiction of a basal rupture of a saccular aneurysm by a small outpouching at the aneurysm neck, this is the first report of saccular aneurysms in which a basal rupture was angiographically depicted as a stalk-like narrow neck due to a thrombus sealing the rupture point and occupying the lumen of the aneurysm base. The author reports on 2 such cases: a 49-year-old woman who presented with a basal rupture of a saccular aneurysm arising at the middle cerebral artery bifurcation, and a 44-year-old man who presented with rupture of a saccular aneurysm arising at the junction of the A(2) segment and the anterior communicating artery. In both cases, a pterional craniotomy allowed the surgeon to determine that the base of the aneurysm was ruptured, and he surgically obliterated the aneurysm. Microsuture reconstruction and clipping of the aneurysm neck were successful in obliterating the ruptured aneurysm and avoiding any compromise of the parent artery. PMID- 20578799 TI - Prognostic factors for the incidence and recovery of delayed facial nerve palsy after vestibular schwannoma resection. AB - OBJECT: Preservation of facial nerve function in vestibular schwannoma (VS) resections remains a significant operative challenge. Delayed facial palsy (DFP) is one specific challenge yet to be fully elucidated. The aim of this study was to evaluate DFP among VS resection cases to identify significant prognostic factors associated with its incidence and clinical recovery. METHODS: This investigation involves a retrospective review of 104 cases of VS resection that occurred between December 2005 and May 2007. Patients who developed DFP were compared with patients exhibiting no facial palsy postoperatively with regard to surgical approach, severity and day of palsy onset, tumor size, intraoperative facial nerve monitoring, and postoperative recovery and treatment. Patients who demonstrated immediate facial palsy (IFP) following VS resection were also analyzed. Furthermore, specific analyses were performed in 2 distinct DFP patient groups: those who developed DFP after postoperative Day 3 ("late onset DFP"), and those whose palsy worsened after initial DFP identification ("deteriorators"). RESULTS: Of the 104 patients who underwent VS resection, 25.0% developed DFP and 8.6% demonstrated IFP postoperatively. The DFP group did not differ significantly in any measure when compared with patients with no postoperative facial palsy. However, patients with DFP presented with significantly smaller tumor sizes than patients with IFP. This IFP group averaged significantly smaller intraoperative facial nerve responses than patients without facial palsy, and larger tumor sizes than both the DFP and no facial palsy groups. Within the DFP group, patients with late onset DFP showed diminished intraoperative facial nerve responses when compared with the total DFP patient population. In total, 25 (96.2%) of 26 patients with DFP and 7 (77.8%) of 9 patients with IFP recovered to normal or near-normal facial function (House-Brackmann Grade I or II) at longest clinical follow-up. CONCLUSIONS: Although patients with DFP did not exhibit any distinguishable characteristics when compared with patients without postoperative facial palsy, our analysis identified significant differences in patients with palsy presenting immediately postoperatively. Further study of patients with DFP should be undertaken to predict its incidence following VS resection. PMID- 20578800 TI - Fenestrated clips. PMID- 20578801 TI - Postoperative seizures following the resection of convexity meningiomas: are prophylactic anticonvulsants indicated? Clinical article. AB - OBJECT: Seizures in the perioperative period are a well-recognized clinical entity in the setting of brain tumor surgery. At present, the suitability of antiepileptic prophylaxis in patients following brain tumor surgery is unclear, especially in those without prior seizures. Given the paucity of tumor-type and site-specific data, the authors evaluated the incidence of postoperative seizures in patients with convexity meningiomas and no prior seizures. METHODS: The authors identified 180 patients with no preoperative history of seizures who underwent resection of a convexity meningioma. Some patients received antiepileptic prophylaxis for 7 days postoperatively while others did not, based on the practice patterns of different attendings. The rates of clinically evident seizures in the first 3-4 weeks after surgery were compared. RESULTS: Patients who received antiepilepsy drugs (129 patients) did not significantly differ from those who did not (51 patients) in terms of age, sex, WHO tumor grade, extent of resection, rate of previous cranial surgery or radiation therapies, or use of preoperative embolization. There was a single new postoperative seizure in the entire cohort, yielding a new seizure rate of 1.9% in patients not on antiepileptic prophylaxis compared with 0% in patients on antiepileptics (p = not significant). CONCLUSIONS: While it is thought that the routine use of prophylactic antiepileptics may prevent new seizures in patients undergoing surgery for a convexity meningioma, the rate of new seizures in untreated patients is probably very low. Data in this study call into question whether the cost and side effects of these medications are worth the small benefit their administration may confer. PMID- 20578802 TI - Traumatic brain injury. PMID- 20578803 TI - Factor XIII. PMID- 20578805 TI - Residual lymph node metastasis in stage 4 neuroblastoma--advantage of radio guided surgery? AB - Log-term prognosis of children suffering from high-risk neuroblastomas is characterized by a shortened event-free survival, especially if metastases remain after chemotherapy. We report the case of a 3-year-old boy afflicted with a stage 4 neuroblastoma and persistent residual lymph node metastases despite the administration of a various number of treatment modalities. The insertion of a MIBG (metaiodobenzylguanidine) single-photon emission computed tomography (SPECT) CT and radio-guided surgery implementing a hand held gamma probe finally allowed the exact localization and resection of the suspected lymphatic tissue. As a consequence, the child has been under event-free remission for 20 months. Because study-based knowledge is missing due to the small number of affected patients, individual case reports are helpful to improve future treatment strategies. PMID- 20578804 TI - Recipient targeting for revascularization using pulsed Doppler ultrasonography for the treatment of an intracranial giant aneurysm. AB - Aneurysmal occlusion after blood flow revascularization is a promising management strategy for the treatment of intracranial giant aneurysms. However, it is necessary to design robust revascularization for preventing postoperative flow related infarctions caused by abrupt occlusion of the parent vessels. Since direct anastomosis of donor vessels to recipient vessels near giant aneurysms is often difficult, it is preferable to select cortical recipient branches away from the aneurysm, thus providing a sufficient working space for the surgeon. In this paper, the authors' goal was to identify distal cortical recipient arteries on the brain surface, based on pulsed Doppler ultrasonography analysis of blood flow alteration after temporary closure of the efferent vessels. This method is used to visualize the area around the sacrificed vessels, omits intraoperative arteriography or the risk of a surgical trace of the vessels by dissecting the distal sulci, and could be advantageous for necessary and sufficient revascularization. PMID- 20578806 TI - The prognostic significance of vanillylmandellic acid in neuroblastoma. AB - The objective of this study was to evaluate urinary vanillylmandellic acid (VMA) as a marker for prognosis and progression of neuroblastoma. A retrospective file search of 444 patients during 33 years was performed and correlation of VMA with clinical prognostic parameters and outcome was evaluated. Event-free survivals (EFS) were 33.5% and 21% (P = .04) and overall survival (OS) were 36.6% and 25.8% (P = .1) for all patients with normal/negative and increased/positive VMA. EFS and OS were higher in VMA(-) pelvic (P = .03) and thoracic and neck (P = .04) tumors, compared to their VMA(+) counterparts. Survival was not different in patients with abdominal primaries according to VMA status. Positive urinary VMA prevalence was low in localized disease and high in disseminated disease (P < .001). In disseminated disease, 10-year EFS was higher in VMA(+) patients than VMA(-) patients (16%, 9.5%, P = .054). Two-year OS was higher in VMA-positive patients with stage 4 disease (20.6% and 7%, P = .04). The patients with VMA(+) progressive disease died later than those with VMA(-) tumors (P = .047). These results show that increased urinary VMA predicts poor outcome for patients with favorable tumor sites. Urinary VMA can be useful risk determinant in combination with other biological determinants to predict prognosis of patients with localized neck, thoracic or pelvic tumors. The relationship of positive or high urinary VMA and survival were inversely correlated in disseminated disease and in patients with progressive disease. In high-risk patients, negative spot test or normal level of urinary VMA at diagnosis might be used for identification of a group of patients with more favorable prognosis. PMID- 20578807 TI - Neutropenic enterocolitis in children and young adults with cancer: prognostic value of clinical and image findings. AB - Intensive chemotherapy regimens can result in severe toxicities, particularly those that involve the digestive systems, leading to morbidity and mortality in this group of patients. Acute enterocolitis can be a frequent complication. The authors performed a retrospective review or patients treated at their institution to ascertain the prognostic value of the clinical symptoms and signs of acute enterocolitis, the corresponding abdominal ultrasonographic findings, and the impact of previous chemotherapy. Amongst 1159 patients with cancer treated at the Centro Infantil Boldrini from 2003 to 2007, 188 (16.2%) patients had 1 or more episode of enterocolitis. An intestinal wall thickness of >or=3 mm on ultrasound was considered diagnostic of enterocolitis. There were 231 episodes of enterocolitis with a death rate of 11.7%. Previous therapy with cytarabine and the presence of abdominal distention affected survival. An intestinal wall thickness of >or=10 mm in the ultrasonographic examination was associated with greater mortality. In multivariate analysis, age, gender, tumor type, degree of neutropenia, intestinal wall thickness, and number of intestinal segments were not statistically significant difference. In children and young adults with cancer and enterocolitis, the clinical findings of 4 or more symptoms and presence of abdominal distention were associated with higher risk of death. Use of cytarabine and an intestinal wall thickness of >or=10 mm were associated with a higher death rate. PMID- 20578808 TI - L-asparaginase-induced pancreatitis in children with acute lymphoblastic leukemia: is allopurinol protective? PMID- 20578809 TI - Invasive respiratory aspergillosis is a treatable disease with early diagnosis and aggressive therapy. AB - This study aimed to document outcome of invasive respiratory aspergillosis (IRA) in pediatric malignancy patients. Patients with febrile neutropenia episodes followed between January 2003 and May 2007 were enrolled. Antifungal therapy was added to those who were still febrile on the 5th day of febrile neutropenia treatment. Patients were screened with computerized tomographies. IRA was identified in 22 of 98 patients. There were 13 males and the mean age was 97 months. Proven infection was established in 3, probable in 7, and possible in 12 patients. Liposomal amphotericin B was administered to all patients and was successful in 10 patients. Modifications with caspofungin or voriconazole were done in liposomal amphotericin B failures. The median duration of antifungal therapy was 5.5 months. The median follow-up time was 29 months. There was no evidence of IRA in 12 patients after completion of cancer chemotherapy. Six patients died due to underlying disease, whereas IRA was either in remission or stable disease. Four patients were lost due to IRA. The remission rate for IRA was 82%. Survival at 37 months was 55% (95% confidence interval 25-47 months). The amount of time that absolute neutrophil count after initiation of treatment for IRA remained at zero was found to be an independent prognostic factor on survival (P = .01). These results suggest that early diagnosis and aggressive treatment may increase the successful outcome of IRA. PMID- 20578810 TI - Platelets: iron fortified? PMID- 20578811 TI - Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study. AB - OBJECTIVE: To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain. RESEARCH DESIGN: Patients (N = 981) were randomized 1:1:1 to receive tapentadol ER 100 - 250 mg b.i.d., oxycodone HCl controlled release (CR) 20 - 50 mg b.i.d., or placebo over 15 weeks (3-week titration period, 12-week maintenance period). MAIN OUTCOME MEASURES: Efficacy was assessed as change from baseline in average pain intensity (11-point NRS) at week 12 of the maintenance period and throughout the maintenance period; last observation carried forward was used to impute missing pain scores. Adverse events (AEs) were monitored throughout the study. RESULTS: Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 (least squares mean difference vs placebo [95% confidence interval], -0.8 [ 1.22, -0.47]; p < 0.001) and throughout the maintenance period (-0.7 [-1.06, 0.35]; p < 0.001). Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 (-0.9 [-1.24,-0.49]; p < 0.001) and throughout the maintenance period (-0.8 [-1.16,-0.46]; p < 0.001). Tapentadol ER was associated with a lower incidence of treatment-emergent AEs (TEAEs) than oxycodone CR. Gastrointestinal TEAEs, including constipation, nausea, and vomiting, were among the most commonly reported TEAEs (placebo, 26.3%; tapentadol ER, 43.7%; oxycodone CR, 61.9%). The odds of experiencing constipation or the composite of nausea and/or vomiting were significantly lower with tapentadol ER than with oxycodone CR (both p < 0.001). CONCLUSIONS: Tapentadol ER (100 - 250 mg b.i.d.) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR (20 - 50 mg b.i.d.). PMID- 20578812 TI - Fundamental solutions to the bioheat equation and their application to magnetic fluid hyperthermia. AB - Methods of predicting temperature profiles during local hyperthermia treatment are very important to avoid damage to healthy tissue. With this aim, fundamental solutions of Pennes' bioheat equation are derived in rectangular, cylindrical, and spherical coordinates. The medium is idealised as isotropic with effective thermal properties. Temperature distributions due to space- and time-dependent heat sources are obtained by the solution method presented. Applications of the fundamental solutions are addressed with emphasis on a particular problem of Magnetic Fluid Hyperthermia (MFH) consisting of a thin shell of magnetic nanoparticles in the outer surface of a spherical solid tumour. It is observed from the solution of this particular problem that the temperature profiles are strongly dependent on the distribution of the magnetic nanoparticles within the tissue. An almost uniform temperature profile is obtained inside the tumour with little penetration of therapeutic temperatures to the outer region of healthy tissue. The fundamental solutions obtained can be used to develop boundary element methods to predict temperature profiles with more complicated geometries. PMID- 20578813 TI - Diagnosis of Toxoplasma gondii infection after allogeneic stem cell transplant can be difficult and requires intensive scrutiny. AB - Infectious complications remain a major problem after allogeneic hematopoietic stem cell transplant (HSCT). Specifically Toxoplasma gondii infection is a life threatening condition in immunocompromised patients. In order to highlight the difficulties in obtaining an early and definitive diagnosis, we report three cases of toxoplasmosis after HSCT for hematologic malignancies: two cases of T. gondii retinochoroiditis, and one case of encephalitis. All patients had unrelated donors and received antithymocyte globulin; none had received trimethoprim/sulfamethoxazole prophylaxis. Toxoplasmosis occurred early post transplant and diagnosis was obtained by real-time PCR. In one case, the correct diagnosis could only be established by PCR analysis of a retinal biopsy specimen. Rapid diagnosis--by invasive approaches--and an immediate onset of antiparasite treatment are crucial to avoid disseminated and often lethal Toxoplasma infections in the post-transplant period. Post-transplant prevention strategies and treatment to control advanced infection in this setting are discussed. PMID- 20578814 TI - Hairy cell leukemia with ascites: an unusual presentation. PMID- 20578815 TI - Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. AB - We conducted a multi-center phase II trial of gemcitabine (G), carboplatin (C), dexamethasone (D), and rituximab (R) in order to examine its safety and efficacy as an outpatient salvage regimen for lymphoma. Fifty-one patients received 2-4 21 day cycles of G (1000 mg/m(2), days 1 and 8), C (AUC = 5, day 1), D (40 mg, daily days 1-4), and R (375 mg/m(2), day 8 for CD20-positive disease) and were evaluable for response. Characteristics included: median age 58 years (19-79 years), stage III/IV 88%, elevated LDH 33%, median prior therapies 2, prior stem cell transplant 12%, chemoresistant 62%, median prior remission duration 2.5 months. The overall and complete response rates were 67% (95% confidence interval [CI] 54-80%) and 31% (95% CI 19-44%), respectively, with activity seen in a broad variety of histologies. Responses occurred in 16 of 17 (94%, 95% CI 83-100%) transplant-eligible patients and 15 of 28 (54%, 95% CI 34-71%) with chemoresistant disease. The median CD34 yield in patients attempting peripheral blood stem cell (PBSC) collection following this regimen was 10.9 x 10(6) CD34+ cells/kg (range 5.0-24.1 x 10(6)). Hematologic toxicity was common, but febrile neutropenia (2.5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma, and successfully mobilizes PBSCs. PMID- 20578816 TI - Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients. AB - The aim of this study was to investigate the efficacy of combined treatment with rituximab and subcutaneous cladribine in patients with newly diagnosed and relapsed chronic lymphocytic leukemia (CLL). Forty-three patients with active CLL or small lymphocytic lymphoma received rituximab 375 mg/m(2) on day 1 and cladribine 0.1 mg/kg subcutaneously on days 2-6. The treatment was repeated every 4 weeks for a total of four cycles. Sixteen patients were pretreated. The overall response rate was 88% (50% complete remission and 38% partial remission). The median time to treatment failure was 37.9 months. Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL. PMID- 20578817 TI - Post-transplant lymphoproliferative disorder after adult-to-adult living donor liver transplant: case series and review of literature. AB - Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplant. Although living donor liver transplant (LDLT) has been increasingly performed, PTLD after LDLT has not been well investigated. We aimed to determine the clinical characteristics of PTLD after LDLT. We investigated 323 consecutive patients undergoing adult-to-adult LDLT and identified three patients who developed biopsy-proven PTLD. All of them were seropositive for Epstein-Barr virus (EBV) and had hepatitis C virus-related cirrhosis at transplant. All three patients developed late-onset and monomorphic PTLD, including one diffuse large B cell lymphoma and two Burkitt lymphomas with c-myc rearrangement. Two of them were EBV negative. The initial therapy included chemotherapy, rituximab, and immunosuppression withdrawal. One patient died of sepsis during treatment and two patients achieved complete responses. We showed a relatively low incidence and distinct clinicopathological features of PTLD after adult-to-adult LDLT, which might reflect the unique nature of LDLT. PMID- 20578818 TI - beta-Tryptase up-regulates vascular endothelial growth factor expression via proteinase-activated receptor-2 and mitogen-activated protein kinase pathways in bone marrow stromal cells in acute myeloid leukemia. AB - Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities. Recently, significant amounts of tryptases have been shown to be produced by myeloblasts in certain patients with acute myeloid leukemia (AML), but the function of secreted tryptases in pathological circumstances remains unknown. In this study, we investigated whether beta-tryptase affects the expression of vascular endothelial growth factor (VEGF) in bone marrow stromal cells (BMSCs) in AML. We detected the expression of proteinase-activated receptor 2 (PAR-2) on AML BMSCs and found that beta-tryptase significantly up-regulated VEGF mRNA and protein expression in a dose-dependent manner by real-time PCR, Western blot, and ELISA. Furthermore, beta-tryptase increased ERK1/2 and p38MAPK phosphorylation, and pretreatment with FLLSY-NH(2), PD98059, and SB230580 (PAR-2, ERK1/2, and p38MAPK inhibitors, respectively) inhibited the beta-tryptase-induced production of VEGF. These results suggest that beta-tryptase up-regulates VEGF production in AML BMSCs via the PAR-2, ERK1/2, and p38MAPK signaling pathways. PMID- 20578820 TI - Genetic variation in tumor necrosis factor and risk of diffuse large B-cell lymphoma and follicular lymphoma: differences between subgroups in Swedish patients. PMID- 20578819 TI - Monitoring bortezomib therapy in multiple myeloma: screening of cyclin D1, D2, and D3 via reliable real-time polymerase chain reaction and association with clinico-pathological features and outcome. AB - Cyclins D1, D2, and D3 (CCND1, 2, 3) are regulated by proteasomal degradation. Their overexpression in multiple myeloma (MM) has prognostic value. We performed this pilot study to analyze a possible association between CCND1-3 overexpression and response to treatment with the proteasome inhibitor bortezomib, since a specific prognostic marker for bortezomib response has not been reported, but would be ideal to predict who benefits most from bortezomib in times of several potentially efficient therapeutic options. Bone marrow (BM) specimens of 20/47 consecutive patients were available for reliable CCND1-3 analyses by real-time PCR. With CCND1 overexpression in 9/20 patients, the risk for progression after bortezomib treatment was significantly decreased (HR 0.102, 95% CI 0.021-0.498, p = 0.0048) and progression-free survival substantially prolonged (p = 0.0011). Our study is the first to suggest that overexpressed CCND1 in MM is an independent prognostic marker associated with a more durable response to bortezomib. These preliminary results warrant a larger study. PMID- 20578821 TI - Coexistence of different types of biallelic immunoglobulin heavy variable gene replacement events in a case of pediatric B precursor acute lymphoblastic leukemia. PMID- 20578822 TI - Individualizing cancer therapy. PMID- 20578823 TI - Cardiac sparing with proton therapy in consolidative radiation therapy for Hodgkin lymphoma. PMID- 20578824 TI - New angles of attack in the fight against chronic lymphocytic leukemia: the advent of novel non-chemotherapeutic agents. AB - Therapeutic outcomes in chronic lymphocytic leukemia (CLL) have improved markedly with the introduction of potent chemoimmunotherapy regimens capable of regularly debulking the disease to a state of complete remission. However, current combinations are reaching the limits of tolerability and effectiveness. As the major toxicities of treatment are myelosuppression and opportunistic infections, the choice of additional agents to add to current combinations must focus on agents with reduced propensity to these complications, as well as agents that have novel mechanisms of action distinct from DNA damage. In addition, patients with comorbid conditions have not benefited from recent developments in combination treatment due to poor tolerance of chemoimmunotherapy regimens. Therefore, we seek to review the mechanism of activity and therapeutic results of the most promising novel agents in CLL, in order to determine how these agents may be best incorporated into future treatment algorithms of both younger/fit patients and patients with comorbidities. PMID- 20578826 TI - Attenuation of Heat-induced Hypothalamic Ischemia, Inflammation, and Damage by Hyperbaric Oxygen in Rats. AB - The present study was attempted to assess the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO2; 100% O2 at 253 kpa) in treating experimental heatstroke. Anesthetized rats were divided into five major groups: the normothermic control (NC) rats treated with normobaric air (NBA; 21% O2 at 101 kpa) (NC+NBA), the NC rats treated with HBO2 (NC+HBO2), the heatstroke (HS) rats treated with NBA (HS+NBA), the HS rats treated with hyperbaric air (HBA; 21% at 253 kpa) (HS+HBA), and the HS rats treated with HBO2 (HS+HBO2). The HS groups were exposed to heat (43o) for exactly 68 min and then allowed to recover at 26oC. HBA or HBO2 was adopted 68 min or 78 min after the start of heat exposure. The survival time values for (HS+NBA) rats, (HS+HBA) rats at 68 min, (HS+HBA) rats at 78 min, (HS+HBO2) rats at 68 min, and (HS+HBO2) rats at 78 min were found to be 90+/-3 mins, 133+/-12 mins, 109+/-9 mins, 240+/-18 mins, and 170+/-15 mins, respectively. Resuscitation with HBA or HBO2 at 68 mins was superior to those treated at 78 mins in prolonging the survival time values. All (HS+NBA) animals displayed hyperthermia, hypotension, and increased cellular levels of ischemia, oxidative stress and damage markers, pro-inflammatory cytokines and an indicator of polymorphonuclear cells accumulation in their hypothalamus as compared to those of normothermic controls. The heat-induced hyperthermia was not affected by HBA or HBO2 treatment. However, heat-induced hypotension and hypothalamic ischemia, oxidative stress, neuronal damage, and inflammation were all significantly reduced by HBA or HBO2 therapy. Compared to those of HBA therapy, HBO2 therapy had significantly higher beneficial effect in treating heatstroke. Our results suggested that HBO2 improved heatstroke outcomes in part by restoring normal hypothalamic function. Delaying the onset of HBO2 therapy reduced the therapeutic efficiency. PMID- 20578825 TI - Effect of growth hormone replacement therapy on cognition after traumatic brain injury. AB - Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy. PMID- 20578827 TI - The multivariate concentric square field test reveals behavioral profiles of risk taking, exploration, and cognitive impairment in mice subjected to traumatic brain injury. AB - There is a need for more efficient tests to evaluate functional outcome following experimental traumatic brain injury (TBI), reflecting deficits in cognitive, sensory, and motor functions that are seen in TBI patients. The Multivariate Concentric Square Field (MCSF) test is a relatively new behavioral model that measures exploration, risk taking, risk assessment, and shelter seeking, all of which are evolutionarily-conserved strategies for survival. The multivariate design enables scoring of different functional domains in a single test situation, with a free choice of optional environmental settings. Furthermore, repeated trials permits cognitive effects to be measured. In the present study, 11 anesthetized C57BL6 mice received controlled cortical injury (CCI) (0.5 mm and 3.3 m/sec) over the right parietal cerebral cortex or sham surgery (n = 12). Naive mice (n = 12) not subjected to any surgical procedure were also included. The animals were evaluated in the MCSF test at 2 and 7 days post-surgery, and behavioral profiles were analyzed. The results revealed differences in risk taking and explorative behavior between the sham animals and the animals subjected to trauma. Animals subjected to trauma were characterized by taking more risks and had a higher level of exploration activity, but they sought less shelter. Repeated exposure to the MCSF caused a general decrease in activity in the naive and sham group, while a more specific behavioral impairment was seen in injured mice, suggesting cognitive dysfunction. We submit that the MCSF test is a useful complementary tool for functional outcome evaluation in experimental TBI. PMID- 20578828 TI - Should the guidelines for management of central venous catheters in patients with candidemia be changed now? PMID- 20578829 TI - Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. AB - BACKGROUND: Patients with candidemia frequently have a central venous catheter (CVC) in place, and its early removal is considered the standard of care. METHODS: We performed a subgroup analysis of 2 phase III, multicenter, double blind, randomized, controlled trials of candidemia to examine the effects of early CVC removal (within 24 or 48 h after treatment initiation) on the outcomes of 842 patients with candidemia. Inclusion criteria were candidemia, age >16 years, CVC at diagnosis, and receipt of 1 dose of the study drug. Six outcomes were evaluated: treatment success, rates of persistent and recurrent candidemia, time to mycological eradication, and survival at 28 and 42 days. Univariate and multivariate analyses were performed, controlling for potential confounders. RESULTS: In univariate analysis, early CVC removal did not improve time to mycological eradication or rates of persistent or recurrent candidemia but was associated with better treatment success and survival. These benefits were lost in multivariate analysis, which failed to show any beneficial effect of early CVC removal on all 6 outcomes and identified Acute Physiology and Chronic Health Evaluation II score, older age, and persistent neutropenia as the most significant variables. Our findings were consistent across all outcomes and time points (removal within 24 or 48 h and survival at 28 and 42 days). The median time to eradication of candidemia was similar between the 2 study groups. CONCLUSIONS: In this cohort of 842 adults with candidemia followed up prospectively, early CVC removal was not associated with any clinical benefit. These findings suggest an evidence-based re-evaluation of current treatment recommendations. PMID- 20578831 TI - Antitumor mechanism of recombinant murine interleukin-12 vaccine. AB - This study was designed to establish an interleukin-12 (IL-12)-expressing murine Lewis lung carcinoma (LLC) cell vaccine (LLC/murine IL-12 [mIL-12]) and assess its antitumor efficacy and mechanism in vivo. The recombinant IL-12 plasmid was transfected into LLC cells and screened by G418, and positive clones were obtained. C57BL/6 tumor-bearing mouse model was established and tumor-bearing mice were randomly divided into three groups (n = 20), that is, treated with an intratumoral injection of phosphate-buffered solution, blank plasmid, or LLC/mIL 12 vaccine, respectively, at days 0, 7, and 14. Tumor size was measured before and after treatment. Tumor growth curve was plotted, cytolytic T lymphocyte (CTL) activity assay and natural killer (NK) cell activity assay were performed, CD4(+) and CD8(+) T lymphocyte were quantitated using flow cytometry, and the expression of interferon-gamma (IFN-gamma), IL-12, and interferon-inducible protein-10 (IP 10) in serum was detected by ELISA. Microvessel density was determined by immunohistochemistry after all mice were euthanized at day 21. The study revealed suppressed tumor growth, elevated levels of IFN-gamma, IP-10, and IL-12, augmented NK and CTL cell activities, and decreased microvessel density of tumor tissues. There were abundant CD4(+) and CD8(+) T lymphocyte infiltration in the vaccine group. This study demonstrated that the antitumor mechanism of LLC/mIL-12 vaccine was to promote IFN-gamma and IL-12 secretion, augment the NK and CTL cell activities, and decrease the microvessel density of tumors. PMID- 20578830 TI - Positive progress in immunoPET--not just a coincidence. AB - The identification of tumor tissue biomarkers has led to the production, validation, and Food and Drug Administration-approval of a number of antibody based targeted therapeutics in the past two decades. As a result of the significant role that these immunotherapeutics play in the management of cancer, and the potential utility of complementary imaging agents, immunoPET imaging has generated considerable interest. This update discusses the important factors to consider when designing a PET (positron emission tomography) imaging agent from the molecular target to the biological targeting molecule and radionuclide combination and also reviews recent preclinical and clinical findings in the immunoPET field. Although there are a variety of radionuclides that are currently utilized in PET studies, this update focuses on four of the positron emitters commonly used in labeling proteins: iodine-124, zirconium-89, copper-64, and fluorine-18. Notable advances in the preclinical setting include the continued development of immunoPET probes to predict the biodistribution of related radioimmunotherapeutics, the success of nontraditional radionuclide and antibody fragment combinations, the broader use of zirconium-89, and the recent emergence of (18)F-labeled diabodies for same-day imaging. Antibody-based PET probes constitute a valuable class of molecular imaging agents, and the progress made preclinically should expedite the transition of these targeted diagnostics to clinical applications. PMID- 20578832 TI - Generation and characterization of non-small-cell lung cancer cell lines and clones for use in the study of immunotherapy. AB - The in vitro study of cancer has been made easier by the use of stable tumor cell (TC) lines derived from patients to study antigen expression, immunogenicity, and response to both experimental and conventional therapeutic agents. However, the routine generation of these cell lines in some tumor histologies such as non small-cell lung cancer (NSCLC) is difficult. In many cases, colonies of TCs do not survive, most likely due to a lack of critical growth factors in cell culture medium. Other times, TC colonies are overgrown by fibroblasts, which appear to have less stringent growth requirements. In some cases, cultures are overgrown by bacteria or mold contained in the biopsy arriving from the surgical or pathology suite. This study presents the characteristics of three new NSCLC cell lines and associated autologous clones generated from both adenocarcinoma and squamous cell carcinoma tissue. Different culture media and variable techniques were used to generate these stable TC lines. Limiting dilution analysis resulted in numerous clones, some of which displayed heterogeneity in terms of growth, antigen expression, and the ability to release cytokines. The successes and failures associated with generating TC lines are discussed in this article. Both parental cultures and related clones serve as critical reagents for the continued study of the cellular immune response to NSCLC. PMID- 20578833 TI - Potential of optimal preloading in anti-CD20 antibody radioimmunotherapy: an investigation based on pharmacokinetic modeling. AB - Recently, it has been suggested that the concept of preloading is limited by using a standard amount of unlabeled antibody. To identify the potential of optimal preloading, a pharmacokinetic model that describes the biodistribution of anti-CD20 antibody was developed. Simulations were conducted for different tumor burdens, spleen sizes, and tumor permeabilities. The optimal amount of unlabeled antibody was determined for each scenario. These simulations show that the currently administered standard amount is not optimal. A preload of 150 mg or lower would result in equal or higher tumor uptake in all cases. For tumors with high permeability, the uptake of labeled antibody could be increased by a factor of 8.5 using the considerably reduced optimal preload. The most sensitive parameter for the choice of the optimal amount of unlabeled antibody is the tumor uptake index. The results indicate that a personalized approach for radioimmunotherapy (RIT) with anti-CD20 antibody is required to account for the interpatient variability. The optimal amount of unlabeled antibody, which has to be determined by using a pharmacokinetic model, could substantially improve tumor uptake and thus RIT with anti-CD20 antibody. PMID- 20578835 TI - Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. AB - Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting. PMID- 20578834 TI - The ultrastructural study of tumorigenic cells using nanobiomarkers. AB - Despite recent advances, patients with malignant brain tumors still have a poor prognosis. Glioblastoma (WHO grade 4 astrocytoma), the most malignant brain tumor, represents 50% of all astrocytomas, with a median survival rate of <1 year. It is, therefore, extremely important to search for new diagnostic and therapeutic approaches for patients with glioblastoma. This study describes the application of superparamagnetic nanoparticles of iron oxide, as well as monoclonal antibodies, of immunophenotypic significance, conjoined to quantum dots for the ultrastructural assessment of glioblastoma cells. For this proposal, an immunophenotypic study by flow cytometry was carried out, followed by transmission electron microscopy analysis. The process of tumor cell labeling using nanoparticles can successfully contribute to the identification of tumorigenic cells and consequently for better understanding of glioblastoma genesis and recurrence. In addition, this method may help further studies in tumor imaging, diagnosis, and prognostic markers detection. PMID- 20578836 TI - Relationship between biological marker expression and fluorine-18 fluorodeoxyglucose uptake in incidentally detected thyroid cancer. AB - The aim of this study was to investigate the underlying mechanisms associated with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in an incidentally detected thyroid cancer during nonthyroid cancer evaluation. Among 92 patients (10 men and 82 women; mean age, 56.2 +/- 10.9 years; age range, 26-78 years) with focal thyroid FDG uptake during nonthyroid cancer evaluation, 14 patients with cytologically confirmed papillary thyroid cancer were included. For semiquantitative analysis, the maximal standardized uptake value was calculated. Immunohistochemical studies were performed for hypoxia inducible factor 1 alpha (HIF1alpha), HIF2alpha, glucose transporter 1 (GLUT1), GLUT3, carbonic anhydrase IX (CA-IX), hexokinase type II (HK II), and vascular endothelial growth factor (VEGF). The significant findings of this study were as follows: (1) a lack of HIF1alpha and HIF2alpha expression; (2) low-degree expression of GLUT1 (1 patient), GLUT3 (5 of 14 patients), HK II (3 of 14 patients), and CA-IX (1 patient); and (3) high degree expression of VEGF (all 14 patients). The data presented in this study indicate that F-18 FDG uptake in incidentally detected thyroid cancer was not related to hypoxia-induced upregulation of GLUT1, GLUT3, CA-IX, and HK II. Ki-67 expression was not associated with F-18 FDG uptake. However, all incidentally detected thyroid cancers showed a high degree of expression of VEGF. PMID- 20578838 TI - Antiproliferative effects of 111In- or 177Lu-DOTATOC on cells exposed to low multiplicity-of-infection double-deleted vaccinia virus encoding somatostatin subtype-2 receptor. AB - Oncolytic viruses may be limited in their ability to infect and lyse tumor cells because of penetration barriers and viral elimination by the immune system. Combining virotherapy with targeted radiotherapy that uses (111)In- or (177)Lu DOTATOC may address such issues by spatially enhancing antitumor effects through bystander and/or cross-fire phenomena. In this study, a double-deleted vaccinia virus (vvDD) encoding the gene for somatostatin subtype-2 receptor (sstr-2) infected MC-38 murine colon adenocarcinoma cells and increased their sstr-2 expression by 2-fold. A low multiplicity-of-infection (MOI = 0.1) of vvDD and short exposure time (48 hours) preserved MC-38 viability (>80%-90%) for up to 3 days, permitting targeting of sstr-2 by (111)In- or (177)Lu-DOTATOC. (111)In DOTATOC, alone or in combination with vvDD, was less effective than (177)Lu DOTATOC at decreasing the growth of sstr-2-gene-transfected human embryonic kidney (HEK)-293 cells or MC-38 cells in monolayer. However, (111)In- or (177)Lu DOTATOC combined with vvDD provided equivalent growth inhibition of HEK-293 or MC 38 cells as spheroids, suggesting a bystander effect from (111)In-DOTATOC. Growth of the cells was reduced 4-fold (from 20% to <5%) at 8 days in this case. Further evaluation of low-MOI vvDD in combination with (111)In- or (177)Lu-DOTATOC for the treatment of MC-38 tumors in mice is planned. PMID- 20578837 TI - Activated PI3K/Akt/COX-2 pathway induces resistance to radiation in human cervical cancer HeLa cells. AB - Activation of Akt, or protein kinase B, is frequently observed in human cancers. It has been demonstrated that PI3K activation leads to radiation resistance. Here, the role of PI3K/Akt/COX-2 pathway in the resistance to radiation in human cervical cancer HeLa cells is explored. Cultured HeLa cells were randomly assigned to five treatment groups: control, radiation, LY294002, PI3K antagonist, and the COX-2-antagonist celecoxib, with the objective of determining the role of PI3K/Akt/COX-2 pathway in the radiation resistance of HeLa cells. The cell survival ratios were computed by clone formation. To calculate the quasi threshold dose (Dq), mean lethal dose (D(0)), survival fraction at 2 Gy radiation dose (SF(2)), and radiosensitization ratio, the cell survival curves were fitted to the one-hit multitarget model. The protein expression profiles for pAkt, Akt, COX-2, Bad, and pBad were detected by Western blot analysis, and the mRNA expression profiles for COX-2 and Bad were analyzed by RT-polymerase chain reaction. Treatment with a combination of celecoxib, LY294002, and radiation resulted in elevated Dq, D(0), and SF(2), and increased radiosensitivity in HeLa cells. The PI3K/Akt/COX-2 pathway was activated by radiation, whereas celecoxib inhibited the activation of the PI3K/Akt/COX-2 axis through several targets. Our results indicate that the activated PI3K/Akt/COX-2 signal transduction pathway was the main cause for decline in radiosensitivity in HeLa cells. This study proposes that the inhibition of the PI3K/Akt/COX-2 pathway can synergistically enhance radiation efficacy. PMID- 20578839 TI - Enzymatic synthesis of uracil glucuronide, labeling with 125/131I, and in vitro evaluation on adenocarcinoma cells. AB - Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% +/- 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled (125/131)I-UNG and (125/131)I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of (125/131)I-UOG were higher than those of (125/131)I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of (125/131)I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I 125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages. PMID- 20578840 TI - A pilot study on the feasibility of real-time calculation of three-dimensional dose distribution for (153)Sm-EDTMP radionuclide therapy based on the voxel S values. AB - OBJECTIVE: Using (153)Sm-EDTMP therapy for bone metastases from nasopharyngeal cancer (NPC), we attempted a real-time three-dimensional (3D) dose calculation based on the S-value for voxels. The 3D radionuclide uptake data on SPECT images were factored into the precalculations by the Monte Carlo (MC) method. METHODS: For the nuclide (153)Sm, the S-value for voxels of size 3.45 x 3.45 x 3.45 mm(3) in a soft tissue phantom was precalculated on a self-developed program built from the MC program EGS4. Based on the SPECT/CT image of the patient, the 3D dose rate distributions were calculated with the S-value method and compared with the direct MC calculation results. The total volume of the whole calculation region and the bone were chosen as the regions of interest (ROIs); additionally, the dose rate volume histograms (DVHs) for the ROIs were also calculated. RESULTS: The iso-dose was administered based on the scan images obtained at 6 hours following injection with the nuclide. In the calculation region, the maximum dose rate was 5.98 x 10(-5) and 6.26 x 10(-5) mGy/(MBq S) for S-value and direct MC calculations, respectively. Once the dose rate was normalized to the maximum dose rate point, the iso-dose curves for both methods of calculation were similar in most regions and reasonably matched the functional image as well. The DVHs of the ROIs indicated that the dose rate distributions were nonuniform, that is, approximately 30% of the bone-ROI volume received 10% of the maximum dose rate; however, only 3.8% volume received 50% of the maximum dose rate. CONCLUSIONS: Using (153)Sm-EDTMP therapy for bone metastases from NPC, we attempted to supplement the current dosimetry work at the image-level by a pragmatic and real time dosimetry calculation based on S-value and functional imaging. More accurate dose calculations for patients undergoing radionuclide therapy will depend on the development of higher image resolution in nuclear medicine and warrant further studies to optimize the pharmacokinetics model. PMID- 20578841 TI - Preparation and in vitro evaluation of 131I-BmK CT as a glioma-targeted agent. AB - OBJECTIVE: Buthus martensi Karsch (BmK) CT, a kind of scorpion toxin peptide, was found to inhibit glioma cell proliferation in previous researches. (131)I-BmK CT may have more inhibition effect and could be used as a glioma cell-targeted therapy and imaging agent. The purpose of this study was to investigate whether (131)I-BmK CT could specifically conjugate with C6 glioma cell and induce glioma cell inhibition in vitro. METHODS: After cloning, expression, and purification, BmK CT was labeled with (131)I by indirect labeling (Bolton-Hunter method). The cell conjugation experiment was performed to investigate the connection between the reciprocal of cell conjugation rate and the reciprocal of cell count. 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method and flow cytometry were used to detect the inhibition effect of BmK CT and (131)I-BmK CT on glioma cell proliferation. RESULTS: (131)I-BmK CT was successfully prepared with the overall yield of 34.5%. The cell conjugation experiment indicated that (131)I-BmK CT could specifically conjugate with C6 cells. MTT tests indicated that both BmK CT and (131)I-BmK CT could inhibit C6 growth. The ability of (131)I BmK CT to inhibit cell growth is superior to that of BmK CT. The inhibitory rate (IR) of glioma cells was 60.5% (p < 0.01) at the concentration of 2 microg/mL with BmK CT. And the IR was 71.2% (p < 0.01) at the radioactivity concentration of 50 microCi/mL (concentration was much lower than 2 microg/mL) with (131)I-BmK CT. BmK CT could block the C6 glioma cell cycle in the G0/G1 stage. (131)I-BmK CT blocked the cell cycle in the S stage (the proportions of C6 in the S, G0/G1, and G2/M phases were 24.5% +/- 0.4% vs. 44.0% +/- 2.3%, 63.9% +/- 0.6% vs. 51.8% +/- 1.6%, and 11.6% +/- 1.0% vs. 4.3 +/- 0.7% [p < 0.05], respectively, at an initial radioactivity concentration of 50 microCi/mL). CONCLUSIONS: On the basis of cytology experiments, it was found that (131)I-BmK CT could specifically conjugate with C6 glioma cell and inhibit cell growth. Hence, it may be used as a glioma-targeted agent. PMID- 20578843 TI - Review of positron emission tomography tracers for imaging of tumor hypoxia. AB - Hypoxia plays a critical role in tumor development and aggressiveness and is an important prognostic factor for resistance to antineoplastic treatments; therefore, it is required to measure the hypoxic level of tumor for a favorable outcome. The pretherapy information on the oxygenation status of a tumor microenvironment should also have implications for treatment selection. A diffuse distribution of hypoxia in a tumor might suggest a benefit from a systemic approach, such as a hypoxic cell cytotoxin, tirapazamine, or antigrowth factor drugs to combat the limitations of hypoxia. Alternatively, a more focal hypoxia might benefit from a local/regional approach, such as intensity-modulated radiation therapy-based radiation dose escalation to the hypoxic subvolume. This review anticipates that (18)F-FMISO ((18)F-fluoromisonodazole) and (64)Cu-ATSM positron emission tomography (PET) will prove useful for selecting individual patients for the most appropriate treatment. The advent of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated PET radiotracer for hypoxia to date being (18)F-FMISO. This article discusses the relevance and biology of hypoxia in cells and organ systems and reviews the laboratory and clinical applications of (18)F-FMISO and other agents in oncology. PMID- 20578842 TI - Stability of 3'-deoxy-3'-[18F]fluorothymidine standardized uptake values in head and neck cancer over time. AB - The purpose of this study was to evaluate the consistency of 3'-deoxy 3'[(18)F]fluorothymidine (FLT) standardized uptake values (SUVs) over the time course of imaging in head and neck cancer. Thirteen (13) subjects (all male; age: 56.9 +/- 6.7 years) with squamous cell head and neck cancer, stage III/IV, were administered FLT and imaged dynamically for 1 hour over the tumor and then underwent whole-body (WB) imaging commencing at 74 +/- 6 minutes. Imaging was repeated after 5 days of radiotherapy (10 Gy) and a single course of platinum based chemotherapy. Volumes-of-interest (VOIs) were created on the last dynamic frame (SUV(60)). The pretherapy WB and midtherapy images were coregistered to the dynamic sequence and VOIs were applied. Mean and maximum SUVs (SUV(60) and SUV(WB)) and the change with treatment were evaluated. The correlations (Spearman's rho) between SUV(60) and SUV(WB) for all VOIs (pre- and midtherapy, n = 108 data pairs) were 0.98 for mean and 0.97 for maximum SUVs (p < 0.0001). Average absolute differences between SUV(60) and SUV(WB) were 0.18 +/- 0.15 and 0.29 +/- 0.32 SUV units, respectively. Correlations (Spearman's rho) between the change in SUV with therapy were 0.90 for mean and 0.89 for maximum SUV (p < 0.0001), with differences in the change values averaging 0.03 +/- 0.36 and -0.17 +/- 0.57 units, respectively. FLT SUVs are stable and comparable for images initiated between 55 and 100 minutes postinjection whether acquired pre- or midtherapy in head and neck cancer. PMID- 20578844 TI - Digestive challenges for vertebrate animals: microbial diversity, cardiorespiratory coupling, and dietary specialization. AB - The digestive system is the interface between the supply of food for an animal and the demand for energy and nutrients to maintain the body, to grow, and to reproduce. Digestive systems are not morphologically static but rather dynamically respond to changes in the physical and chemical characteristics of the diet and the level of food intake. In this article, we discuss three themes that affect the ability of an animal to alter digestive function in relation to novel substrates and changing food supply: (1) the fermentative digestion in herbivores, (2) the integration of cardiopulmonary and digestive functions, and (3) the evolution of dietary specialization. Herbivores consume, digest, and detoxify complex diets by using a wide variety of enzymes expressed by bacteria, predominantly in the phyla Firmicutes and Bacteroidetes. Carnivores, such as snakes that feed intermittently, sometimes process very large meals that require compensatory adjustments in blood flow, acid secretion, and regulation of acid base homeostasis. Snakes and birds that specialize in simple diets of prey or nectar retain their ability to digest a wider selection of prey. The digestive system continues to be of interest to comparative physiologists because of its plasticity, both phenotypic and evolutionary, and because of its widespread integration with other physiological systems, including thermoregulation, circulation, ventilation, homeostasis, immunity, and reproduction. PMID- 20578845 TI - First aid kit for hypoxic survival: sensors and strategies. AB - Survival success under conditions of acute oxygen deprivation depends on efficiency of the central and peripheral chemoreception, optimization of oxygen extraction from the hypoxic environment and its delivery to the periphery, and adjustments of energy production and consumption. This article uses a comparative approach to assess the efficiency of adaptive strategies used by anoxia-tolerant and hypoxia-sensitive species to support survival during the first minutes to 1 h of oxygen deprivation. An aquatic environment is much more demanding in terms of diurnal and seasonal variations of the ambient oxygen availability from anoxia to hyperoxia than is an air environment. Therefore, fishes and aquatic turtles have developed a number of adaptive responses, which are lacking in most of the terrestrial mammals, to cope with these extreme conditions. These include efficient central and peripheral chemoreception, acute changes in respiratory rate and amplitude, and acute increase of the gas-exchange interface. A special set of adaptive mechanisms are engaged in reduction of the energy expenditure of the major oxygen-consuming organs: the brain and the heart. Both reduction of ATP consumption and a switch to alterative energy sources contribute to the maintenance of ATP and ion balance in hypoxia-tolerant animals. Hypoxia and hyperoxia are conditions favoring development of oxidative stress. Efficient protection from oxidation in anoxia-tolerant species includes reduction in the glutamate levels in the brain, stabilization of the mitochondrial function, and maintenance of nitric oxide production under conditions of oxygen deprivation. We give an overview of the current state of knowledge on some selected molecular and cellular acute adaptive mechanisms. These include the mechanisms of chemoreception in adult and neonatal mammals and in fishes, acute metabolic adaptive responses in the brain, and the role of nitrite in the preservation of heart function under hypoxic conditions. PMID- 20578846 TI - Physiological mechanisms in coping with climate change. AB - Although many studies have modeled the effects of climate change on future species distributions and extinctions, the theoretical approach most commonly used-climate envelope modeling-typically ignores the potential physiological capacity of animals to respond to climate change. We explore the consequences of the phenotypic plasticity available to animals, by examining physiological responses of free-living animals in their natural habitats and by applying integrative, mechanistic models of heat exchange in invertebrates and humans. Specifically, we explore how behavioral, autonomic, and morphological modifications such as nocturnal activity, selective brain cooling, and body color may potentially serve as buffers to the consequences of climate change. Although some species may adapt to climate change through phenotypic plasticity, there are significant limits to this strategy. Furthermore, predictions of the response of organisms to changes in climate can be erroneous when modeled at large scales using coarse spatial or temporal data. Environmental heterogeneity can provide habitats suitable for species even though large-scale changes in the climate might predict a species' extinction. A detailed understanding of physiology, combined with integrative biophysical modeling and ecological manipulation, provides a powerful tool for predicting future ecological patterns and managing their consequences. PMID- 20578847 TI - Optimized transduction of human monocyte-derived dendritic cells by recombinant adeno-associated virus serotype 6. AB - Dendritic cells are the key antigen-presenting cells involved in the initiation of the adaptive immune response. Recombinant adeno-associated viruses (rAAVs) can transduce dendritic cells and have gained attention as potential vaccines capable of stimulating T cell immunity. Here we show that rAAV2 pseudotyped with type 6 capsid (rAAV2/6) exhibits significantly higher tropism for human monocyte-derived dendritic cells (MoDCs) than other serotypes and variants. Transduction was abolished by a single lysine-to-alanine mutation within the AAV6 capsid previously shown to inhibit binding to heparin. However, unlike rAAV2, soluble heparin did not inhibit rAAV2/6 transduction of MoDCs. Further enhancement of MoDC transduction was observed after mutation of Tyr-731 in the capsid of AAV6 consistent with a report that tyrosine residues are phosphorylated, leading to ubiquitination of capsids during uptake. Pseudotyped rAAV2/6 vectors containing a Y731F mutation minimally altered the immunophenotype of MoDCs, which retained their immunostimulatory ability and were able to stimulate an antigen-specific CD8(+) T cell clone. These findings should assist in the development of rAAV2/6 as a vaccine vector. PMID- 20578848 TI - Comparison of two protocols for maxillary protraction: bone anchors versus face mask with rapid maxillary expansion. AB - OBJECTIVE: To test the hypothesis that there is no difference in the active treatment effects for maxillary advancement induced by bone-anchored maxillary protraction (BAMP) and the active treatment effects for face mask in association with rapid maxillary expansion (RME/FM). MATERIALS AND METHODS: This is a study on consecutively treated patients. The changes in dentoskeletal cephalometric variables from start of treatment (T1) to end of active treatment (T2) with an average T1-T2 interval of about 1 year were contrasted in a BAMP sample of 21 subjects with a RME/FM sample of 34 patients. All subjects were prepubertal at T1. Statistical comparison was performed with t-tests for independent samples. RESULTS: The BAMP protocol produced significantly larger maxillary advancement than the RME/FM therapy (with a difference of 2 mm to 3 mm). Mandibular sagittal changes were similar, while vertical changes were better controlled with BAMP. The sagittal intermaxillary relationships improved 2.5 mm more in the BAMP patients. Additional favorable outcomes of BAMP treatment were the lack of clockwise rotation of the mandible as well as a lack of retroclination of the lower incisors. CONCLUSIONS: The hypothesis is rejected. The BAMP protocol produced significantly larger maxillary advancement than the RME/FM therapy. PMID- 20578849 TI - Long-term follow-up of dental single implants under immediate orthodontic load. AB - OBJECTIVE: To evaluate the success of osseointegrated implants under immediate prosthetic and orthodontic forces after a follow-up period of at least 2 years. MATERIALS AND METHODS: The sample included 20 titanium implants which were used as orthodontic and prosthetic anchorage of immediately loaded single-crowns on a total of 13 patients. A 40 N initial torque was considered the minimum for inclusion in the sample. All implants received screwed provisional crowns immediately after surgery. The implants were randomly divided into two groups: the control group (9 implants) and the immediate orthodontic loading group (11 implants). A healing period of 4 months was observed before orthodontic loads were applied to the control group implants. For the immediate orthodontic loading group, orthodontic forces were applied within 24 hours. The maximum orthodontic force applied in both groups was 200 g. After 6 months of orthodontic movement, clinical and radiographic evaluations were obtained. Implants were considered successful when favorable results were obtained in all evaluations. RESULTS: After a 2-year follow-up, the success rates were 90.9% and 88.9%, respectively, in the orthodontic loading group and the control group. Each group had one failure. CONCLUSION: Shortening the healing period for the application of orthodontic forces did not seem to affect the success of osseointegrated implants used as anchorage. PMID- 20578850 TI - Automatic recognition of anatomic features on cephalograms of preadolescent children. AB - OBJECTIVE: To develop a system that automatically recognizes the dentoskeletal traits on cephalograms recorded for preadolescent children and to examine performance reliability. MATERIALS AND METHODS: We obtained 859 lateral cephalograms and divided them into group P (400 films taken from orthodontic patients having permanent dentition) and group M (459 films taken from those having mixed dentition). Fifty-nine cephalograms in group M were reserved for system test, and the remaining cephalograms in groups M and P were used for system development. Using a previously reported method (Yagi and Shibata, 2003), systems S(M) and S(P+M) were developed with the knowledge generated from groups M and P+M (combined sample of groups M and P), respectively. The system S(P) that had been developed for cephalograms of permanent dentition in our previous report was also employed for comparison. To evaluate performance reliability, the systems examined the 59 reserved cephalograms. The areas of each system identified anatomic structure surrounding the anatomic landmarks and the positions of each system-identified landmark were compared with the norms in the form of confidence ellipses. The success rates were calculated for S(P), S(M), and S(P+M). RESULTS: The systems successfully identified all of the specified anatomic structures in all of the images. The systems S(P), S(M), and S(P+M) determined the landmark positions with a mean success rate of 69% (range, 38 98%), 82% (range, 50-100%), and 82% (range, 58-100%), respectively. CONCLUSIONS: Systems S(M) and S(P+M) were confirmed to be accurate and reliable in recognizing the anatomic features on the cephalograms of preadolescent children. PMID- 20578851 TI - Mechanical properties of self-drilling orthodontic micro-implants with different diameters. AB - OBJECTIVE: The hypothesis to be tested is that peak-insertion torque of self drilling micro-implants of an appropriate diameter correlates with peak-removal torque mechanically. MATERIALS AND METHODS: A total of 360 self-drilling micro implants composed of five different types were used. They (24 of each group) were inserted in three types of artificial bone with the use of a driving torque tester at a speed of 15 rpm. Insertion torque was measured during the placement, while the removal torque was measured within 3 days after insertion. RESULTS: Most of the micro-implants in type A sheared before they were completely inserted in 40-pounds per cubic foot bone. The implants in other types were successfully inserted without implant breakage and bone fracture in all bone densities. There was a statistically significant correlation between insertion torque and removal torque (r > or = 0.43543, P = .0001). There were significant differences in insertion and removal torque among the diameters of implants and bone densities with an increasing tendency. The torque loss rates reduced as the diameter of the implant and bone density increased. CONCLUSIONS: Micro-implants with a diameter of less than 1.3 mm are unsuitable for insertion into a bone with a density greater than 40 pounds per cubic foot mechanically when one is using a self drilling technique. PMID- 20578852 TI - A study on orthodontic bone-bonding anchorage. AB - OBJECTIVES: The study had two objectives: (1) to measure the maximum loading capacity of a new skeletal orthodontic anchorage, designated the "bone-bonding anchorage," and (2) to study its histological basis. MATERIALS AND METHODS: A total of 81 bone-bonding anchorages were fixed onto the surface of the tibia of 12 big-ear white rabbits with N-2-butyl cyanoacrylate. The 12 animals were divided into groups designated as the immediate, 2-week, 4-week, and 8-week after surgery groups. The maximum loading capacity of each group was measured, and histological changes were observed. RESULTS: The results indicate a tendency toward an initial decrease and then an increase in the maximum loading capacity of the bone-bonding anchorage. The mean value of the 8-week group reached 45.69 N, which can satisfy orthodontic clinical needs. Histologically, new bone formation was found around the base of the bone-bonding anchorage, which wrapped the base until it was bone-buried, creating the histological basis of the maximum loading capacity. In the experiment, the total failure rate of the bone-bonding anchorage was 13.6%, and no failure occurred in the immediate and 8-week groups. CONCLUSION: The loading capacity of the bone-bonding anchorage is sufficient for orthodontic use, but whether or not it can be applied to clinical practice merits further study. PMID- 20578853 TI - Condylar displacement between centric relation and maximum intercuspation in symptomatic and asymptomatic individuals. AB - OBJECTIVE: To measure condylar displacement between centric relation (CR) and maximum intercuspation (MIC) in symptomatic and asymptomatic subjects. MATERIALS AND METHODS: The sample comprised 70 non-deprogrammed individuals, divided equally into two groups, one symptomatic and the other asymptomatic, grouped according to the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Condylar displacement was measured in three dimensions with the condylar position indicator (CPI) device. Dahlberg's index, intraclass correlation coefficient, repeated measures analysis of variance, analysis of variance, and generalized estimating equations were used for statistical analysis. RESULTS: A greater magnitude of difference was observed on the vertical plane on the left side in both symptomatic and asymptomatic individuals (P = .033). The symptomatic group presented higher measurements on the transverse plane (P = .015). The percentage of displacement in the mesial direction was significantly higher in the asymptomatic group than in the symptomatic one (P = .049). Both groups presented a significantly higher percentage of mesial direction on the right side than on the left (P = .036). The presence of bilateral condylar displacement (left and right sides) in an inferior and distal direction was significantly greater in symptomatic individuals (P = .012). However, no statistical difference was noted between genders. CONCLUSION: Statistically significant differences between CR and MIC were quantifiable at the condylar level in asymptomatic and symptomatic individuals. PMID- 20578854 TI - Changes in temporomandibular joint disc position and form following Herbst and fixed orthodontic treatment. AB - OBJECTIVE: To determine the changes in the position and form of the temporomandibular joint articular disc in adolescents with Class II division 1 malocclusion and mandibular retrognathism treated with the Herbst appliance (phase I) and fixed orthodontic appliance (phase II). MATERIALS AND METHODS: Thirty-two consecutive adolescents went through phase I of treatment and 23 completed phase II. The temporomandibular joints were evaluated qualitatively by means of magnetic resonance images at the beginning of treatment (T1), during phase I (T2), at the end of phase I (T3), and at the end of phase II (T4). RESULTS: Significant changes in disc position were not observed with the mouth closed between T1 x T3 (P = .317), T3 x T4 (P = .287), or T1 x T4 (P = .261). At T2, on average, the disc was positioned regressively. With the mouth open, no difference was observed between T1 x T3 (P = .223) or T1 x T4 (P = .082). We did observe a significant difference between T3 x T4 (P < .05). Significant changes in the disc form were found with the mouth closed between T1 x T2 (P < .001) and T2 x T3 (P < .001). CONCLUSIONS: At the end of the two-phase treatment, in general terms, the position and form of the initial articular discs were maintained; however, in some temporomandibular joints some seemingly adverse effects were observed at T4. PMID- 20578855 TI - Posterior occlusion changes with a Hawley vs Perfector and Hawley retainer. A follow-up study. AB - OBJECTIVE: To characterize postorthodontic settling of the posterior occlusion of patients wearing Hawley retainers vs patients who initially wore Perfector retainers and then switched to Hawley retainers. MATERIALS AND METHODS: This follow-up study was based on 40 patients (25 Perfector and 15 Hawley), who were part of a larger sample of 50 patients randomly assigned to wear either Hawley or Perfector retainers. The Perfector patients were given Hawley retainers 2 months after retainer delivery. Occlusal bite registrations were scanned and traced to quantify posterior areas of contact and near contact (ACNC). A seven-item questionnaire was used to assess the patient's perception of occlusion. Measurements were obtained at the on the day of retainer delivery, 2 months post delivery, 6 months post delivery, and 8 months post delivery. RESULTS: ACNC increased significantly (P < .05) during the first 6 months of retainer wear. The ACNC of the Hawley and Perfector/Hawley groups increased by 129% and 105%, respectively, over 8 months of retention. The greatest increases in ACNC occurred during the first 2 months. The ACNC further increased between 2 and 6 months in both groups. The Perfector/Hawley group also showed slight increases in ACNC between 6 and 8 months. Overall group differences were not statistically significant. The Perfector/Hawley group perceived greater improvements in occlusion than the Hawley group, but group differences after 8 months were small. CONCLUSIONS: Substantial amounts of settling occurred at decelerating rates during the first 6 months after retainer delivery. No significant differences in ACNC were found between the Hawley and Perfector/Hawley groups after 8 months of retainer wear. PMID- 20578856 TI - Cranial base, maxillary and mandibular morphology in Down syndrome. AB - OBJECTIVE: To test the null hypothesis that there is no difference between craniofacial measurements of individuals with Down syndrome (DS) and normal controls. MATERIALS AND METHODS: A cephalometric analysis including additional landmarks and measurements to study specific craniofacial features was undertaken on pretreatment cephalograms of 25 patients with DS (12 male, 13 female; mean age 15.1 years) treated at The Hospital for Sick Children, Toronto. Measurements were compared with those from cephalograms of racial groups age and gender matched, normal, Class I children, available from the Burlington Growth Center. Data were analyzed using paired t-tests. RESULTS: Large reductions were measured in the size and spatial relationships of craniofacial structures in the DS group. The greatest differences included a larger cranial base angle; reduced elevation of sella from FHP; reduced anterior and posterior cranial base lengths; reduced anterior and posterior face heights; smaller maxilla with reduced anterior basal and apical dimensions; and smaller mandibular ramus, body and symphyseal dimensions and proclined symphysis. Maxillary incisors were severely proclined and undererupted, while mandibular incisors were undererupted. Alveolar heights were reduced. Anterior open bite was frequently noted. Maxillary and mandibular planes exhibited forward rotation patterns, promoting overclosure. Mandibular hypoplasia was less severe than cranial base and maxillary hypoplasia. Hypodontia of one or more permanent teeth was found in 92% of the sample. CONCLUSIONS: The null hypothesis was rejected. Significant hypoplasia in endochondral, mesodermal, and ectomesenchymal derived structures of the cranium and face in subjects with DS was clearly evident. More severe platybasia than previously reported was found. PMID- 20578857 TI - Comparison of the effects of RME and fan-type RME on nasal airway by using acoustic rhinometry. AB - OBJECTIVE: To evaluate and compare the nasal airway changes following rapid maxillary expansion (RME) and fan-type RME using acoustic rhinometry (AR). MATERIALS AND METHODS: The study sample consisted of three groups. The RME group comprised 15 subjects with maxillary transverse discrepancies and posterior crossbites. The fan-type RME group comprised 15 subjects, who had an anteriorly constricted maxilla with a normal intermolar width. The third group included 15 patients who had an ideal occlusion and received no orthodontic treatment and served as the control group. AR was used to measure nasal volume and the minimal cross-sectional area (MCA) before expansion (T1), after expansion (T2), and 6 months after expansion (T3). Each AR recording was performed with and without the use of a decongestant. Two-way analysis of variance was used to determine differences among the groups and three-way analysis of variance was used for the differences between groups. If evidence of statistically significant differences was found, a Bonferroni test was used. RESULTS: The results showed that nasal volume and MCA were significantly increased with RME and fan-type RME immediately after expansion (P < .05). At the end of retention, nasal volume and MCA values of RME showed significant differences with both expansion fan-type RME and control groups (P < .05). CONCLUSIONS: RME and fan-type RME had similar effects on the nasal airway immediately after expansion. The increase in nasal volume and MCA was more stable in the RME group than in the fan-type RME group at the end of the retention period. PMID- 20578858 TI - Assessment of maxillary position. Implant vs cephalometric methods. AB - OBJECTIVE: To compare changes in maxillary position assessed from a maxillary implant and three cephalometric methods based on linear measurements. METHODS: Series of tracings of the maxilla obtained around puberty from an implant study were analyzed. The displacement of the implant was used to determine the direction and amount of "actual" maxillary growth. Displacement of point A was measured according to three cephalometric methods. The values obtained from absolute, horizontal, and vertical displacement of point A by three cephalometric methods and by the implant method were compared. RESULTS: Results showed that estimation of displacement of the maxilla by three cephalometric methods (point A) was significantly larger than that of the implant method in all directions. The average difference in the horizontal plane was 0.7 mm, 1.2 mm, and 1.6 mm, respectively; the average difference in the vertical plane was 2.2 mm, 2.5 mm, and 3.6 mm, respectively. CONCLUSIONS: Estimations of changes in maxillary position by the implant method and by cephalometric methods were not proportional. All three cephalometric methods overestimated changes in the position of the maxilla. PMID- 20578859 TI - A comparison of torque expression between stainless steel, titanium molybdenum alloy, and copper nickel titanium wires in metallic self-ligating brackets. AB - OBJECTIVE: The force moment providing rotation of the tooth around the x-axis (buccal-lingual) is referred to as torque expression in orthodontic literature. Many factors affect torque expression, including the wire material characteristics. This investigation aims to provide an experimental study into and comparison of the torque expression between wire types. MATERIALS AND METHODS: With a worm-gear-driven torquing apparatus, wire was torqued while a bracket mounted on a six-axis load cell was engaged. Three 0.019 x 0.0195 inch wire (stainless steel, titanium molybdenum alloy [TMA], copper nickel titanium [CuNiTi]), and three 0.022 inch slot bracket combinations (Damon 3MX, In-Ovation R, SPEED) were compared. RESULTS: At low twist angles (<12 degrees), the differences in torque expression between wires were not statistically significant. At twist angles over 24 degrees, stainless steel wire yielded 1.5 to 2 times the torque expression of TMA and 2.5 to 3 times that of nickel titanium (NiTi). At high angles of torsion (over 40 degrees) with a stiff wire material, loss of linear torque expression sometimes occurred. CONCLUSIONS: Stainless steel has the largest torque expression, followed by TMA and then NiTi. PMID- 20578860 TI - Cytotoxic effects of resin-modified orthodontic band adhesives. Are they safe? AB - OBJECTIVE: To evaluate the cytotoxic effects of three different resin-modified orthodontic band adhesives. MATERIALS AND METHODS: Three resin-modified orthodontic band adhesives (Bisco Ortho Band Paste LC, Multi-Cure Glass Ionomer Band Cement, and Transbond Plus Light Cure Band Adhesive) were prepared and the samples were extracted in 3 mL of Basal Medium Eagle with 10% newborn calf serum for 24 hours. The L929 cells were plated (25,000 cells/mL) in wells of 96-well dishes and maintained in a humidified incubator for 24 hours at 37 degrees C, 5% CO(2), and 95% air. After 24-hour incubation of the cells, the incubation medium was replaced by the immersed medium in which the samples were stored. Then L929 cells were incubated in contact with eluates for 24 hours. The cell mitochondrial activity was evaluated by the methyltetrazolium test. Twelve wells were used for each specimen, and methyltetrazolium tests were applied two times. The data were statistically analyzed using one-way analysis of variance and Tukey Honestly Significantly Different tests. RESULTS: Results with L929 fibroblasts demonstrated that all freshly prepared resin-modified orthodontic band adhesive materials reduced vital cell numbers (P > .05), in comparison to the control group. Our data demonstrate that all materials showed significant cytotoxicity compared to the control group. CONCLUSIONS: The results indicate that all materials showed significant cytotoxicity compared to the control group, and further studies using different test methods are needed for all resin-modified orthodontic band adhesives. PMID- 20578861 TI - Three-dimensional evaluation of soft tissue change gradients after mandibular setback surgery in skeletal Class III malocclusion. AB - OBJECTIVE: To evaluate whether mandibular setback surgery (MSS) for Class III patients would produce gradients of three-dimensional (3D) soft tissue changes in the vertical and transverse aspects. MATERIALS AND METHODS: The samples consisted of 26 Class III patients treated with MSS using bilateral sagittal split ramus osteotomy. Lateral cephalograms and 3D facial scan images were taken before and 6 months after MSS, and changes in landmarks and variables were measured using a Rapidform 2006. Paired and independent t-tests were performed for statistical analysis. RESULTS: Landmarks in the upper lip and mouth corner (cheilion, Ch) moved backward and downward (respectively, cupid bow point, 1.0 mm and 0.3 mm, P < .001 and P < .01; alar curvature-Ch midpoint, 0.6 mm and 0.3 mm, both P < .001; Ch, 3.4 mm and 0.8 mm, both P < .001). However, landmarks in stomion (Stm), lower lip, and chin moved backward (Stm, 1.6 mm; labrale inferius [Li], 6.9 mm; LLBP, 6.9 mm; B', 6.7 mm; Pog', 6.7 mm; Me', 6.6 mm; P < .001, respectively). Width and height of upper and lower lip were not altered significantly except for a decrease of lower vermilion height (Stm-Li, 1.7 mm, P < .001). Chin height (B' Me') was decreased because of backward and upward movement of Me' (3.1 mm, P < .001). Although upper lip projection angle and Stm-transverse projection angle became acute (Ch(Rt)-Ls-Ch(Lt), 5.7 degrees; Ch(Rt)-Stm-Ch(Lt), 6.4 degrees, both P < .001) because of the greater backward movement of Ch than Stm, lower lip projection angle and Stm-vertical projection angle became obtuse (Ch(Rt)-Li Ch(Lt), 10.8 degrees ; Ls-Stm-Li, 23.5 degrees , both P < .001) because of the larger backward movement of Li than labrale superius (Ls). CONCLUSIONS: Three dimensional soft tissue changes in Class III patients after MSS exhibited increased gradients from upper lip and lower lip to chin as well as from Stm to Ch. PMID- 20578862 TI - Alteration of bFGF expression with growth and age in rat molar periodontal ligament. AB - OBJECTIVE: To test the hypothesis that immunohistochemical changes in expression of basic fibroblast growth factor in the periodontal ligament do not change with age. MATERIALS AND METHODS: Thirty male Wistar-ST rats were divided into growing groups (5, 9, and 15 weeks of age) and aging groups (6, 12, and 18 months of age). Serial sagittal sections (5 microm thick) were cut parallel at the distobuccal roots of the maxillary first molar. Paraffin-embedded tissue sections were stained with hematoxylin and eosin and rabbit polyclonal antibodies to basic fibroblast growth factor. RESULTS: The number and the area of basic fibroblast growth factor-immunoreactive cells in the periodontal ligament of the maxillary first molar decreased with age. The number of basic fibroblast growth factor immunoreactive cells was much greater in the root furcation area, which experiences the greatest effect of occlusal force. Regardless of age, the production of basic fibroblast growth factor in the periodontal ligament may occur subject to functional demand. CONCLUSIONS: The hypothesis is rejected. The expression of basic fibroblast growth factor in the periodontal ligament decreased with age. PMID- 20578863 TI - Orthodontic mechanical tension effects on the myofibroblast expression of alpha smooth muscle actin. AB - OBJECTIVE: To detect myofibroblast formation on the tension side during orthodontic tooth movement in vivo and myofibroblast expression of alpha-smooth muscle actin (alpha-SMA) induced by tension both in vivo and in vitro. MATERIALS AND METHODS: Fifty 6-week male rats were used in this in vivo study, and the right maxillary first molar was moved mesially, which served as the experimental group, and the left maxillary first molar served as the control. Rats were sacrificed at days 0, 3, 5, 7, and 14 after force loading. Myofibroblasts, identified with alpha-SMA, were examined through immunohistochemistry. For the in vitro study, human periodontal ligament (PDL) fibroblasts were obtained. Cyclic mechanical tension was applied to the fibroblasts for 0, 1, 3, 6, and 12 hours. Transmission electron microscopy was used to detect the ultrastructure of myofibroblasts. alpha-SMA mRNA gene expression was quantified by real-time quantitative PCR. The expression of alpha-SMA was detected by immunofluorescence and quantified by Western blotting. RESULTS: In vivo, the myofibroblasts expressing alpha-SMA were identified both in the experimental group and in the control group. The expressions of alpha-SMA were increased in the tension areas of the experimental group over time, and reached the maximum in day 14. In vitro, fibronexus junctions and actin microfilaments in the cells could be found with transmission electron microscopy. Cyclic mechanical tension could significantly induce alpha-SMA expression at 12 hours (P < .01) than the controls. CONCLUSIONS: Myofibroblasts existed in the PDL. The expressions of alpha-SMA in the myofibroblasts were significantly up regulated under tension both in vivo and in vitro. PMID- 20578864 TI - Dental archforms in dentoalveolar Class I, II and III. AB - OBJECTIVE: To test the hypothesis that no differences exist in dental arch dimensions between dentoalveolar Classes I, II, and III, and between male and female subjects, as measured on virtual three-dimensional (3D) models. MATERIALS AND METHODS: Samples included randomly selected plaster dental casts of 137 white patients (43 Class I, 50 Class II, and 44 Class III) from the Department of Orthodontics, School of Dental Medicine, University of Zagreb, Croatia. Dental models were scanned and digitized using ATOS II SO ("Small Objects") scanning technology (GOM mbH, Braunschweig, Germany). Eight linear and two proportional measurements were calculated for both upper and lower dental arches. RESULTS: In men, a significant difference in the upper dental arch was present in the incisor region, and in the lower dental arch, differences were found in intercanine and intermolar widths (P < .05). Significant differences were noted between male groups in the upper molar depth dimension (P = .022) and in the lower molar and canine depth dimensions (P < .05). Class III males had the greatest lower molar and canine width/depth ratios and the smallest lower canine depth/molar depth ratio. Class III women had wider and shorter mandibular arches when compared with Class I and Class II females. CONCLUSION: The hypothesis was rejected. The dimensions of the dental arches are related to gender and to dentoalveolar class. Class I and II subjects have similar dimensions of maxillary dental arch, but Class II subjects have a transverse deficit in the mandible. In Class III subjects, the maxillary dental arch is insufficient in transverse and sagittal dimensions, and the mandibular arch dominates in the transverse but not in the sagittal dimension. PMID- 20578865 TI - Interventions for pain during fixed orthodontic appliance therapy. A systematic review. AB - OBJECTIVE: To compare the different methods of pain control intervention during fixed orthodontic appliance therapy. MATERIALS AND METHODS: A computerized literature search was performed in MEDLINE (1966-2009), The Cochrane Library (Issue 4, 2009), EMBASE (1984-2009), and CNKI (1994-2009) to collect randomized controlled trials (RCTs) for pain reduction during orthodontic treatment. Data were independently extracted by two reviewers and a quality assessment was carried out. The Cochrane Collaboration's RevMan5 software was used for data analysis. The Cochrane Oral Health Group's statistical guidelines were followed. RESULTS: Twenty-six RCTs were identified and six trials including 388 subjects were included. Meta-analysis showed that ibuprofen had a pain control effect at 6 hours and at 24 hours after archwire placement compared with the placebo group. The standard mean difference was -0.47 and -0.48, respectively. There was no difference in pain control between ibuprofen, acetaminophen, and aspirin. Other analgesics such as tenoxicam and valdecoxib had relatively lower visual analog scale (VAS) scores in pain perception. Low-level laser therapy (LLLT) was also an effective approach for pain relief with VAS scores of 3.30 in the LLLT group and 7.25 in the control group. CONCLUSIONS: Analgesics are still the main treatment modality to reduce orthodontic pain despite their side effects. Some long-acting nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase enzyme (COX-2) inhibitors are recommended for their comparatively lesser side effects. Their preemptive use is promising. Other approaches such as LLLT have aroused researchers' attention. PMID- 20578866 TI - Analysis of the effect of CPP-ACP tooth mousse on enamel remineralization by circularly polarized images. AB - OBJECTIVE: To evaluate the effect of casein phosphopeptide-amorphous calcium phosphate tooth mousse on the remineralization of bovine incisor by circularly polarized images. METHODS: Eighty bovine incisors, each with a 4 x 4 mm artificially demineralized area, were used. The samples were divided into four groups: Group A, casein phosphopeptide-amorphous calcium phosphate tooth mousse; Group B, fluoride toothpaste; Group C, casein phosphopeptide-amorphous calcium phosphate tooth mousse and fluoride toothpaste; and Group D, no treatment. Circularly polarized images were taken after the specimens were treated for 3, 6, 9, or 12 weeks, and the size of the demineralized area and the mean grey level were measured. Data analysis was done using repeated measures variance analysis. Pearson correlation coefficients were computed to evaluate the correlation between the size of the demineralized area and the mean grey level. RESULTS: In all four groups, the size of the demineralized area and the mean grey level declined with time. The size of the demineralized area of Group C was significantly smaller than that of Group A at the end of the third and sixth weeks (P = .039, P = .000, respectively), and the mean grey level of Group C was lower than that of Group A at the end of the 6th and 12th weeks (P = .037, P = .004, respectively). At the end of the 6th, 9th, and 12th weeks, the size of the demineralized area of Group C was smaller (P = .000, P = .005, P = .005, respectively) and the mean grey level was lower (P = .000) than those of Group B. No statistically significant correlations were detected between the size of the demineralized area and the mean grey level. CONCLUSION: Casein phosphopeptide amorphous calcium phosphate tooth mousse can reduce the size and mean grey level of demineralized areas and promote the remineralization of bovine enamel. Combined application with fluoride toothpaste strengthens the effect. PMID- 20578867 TI - Optimal sites for orthodontic mini-implant placement assessed by cone beam computed tomography. AB - OBJECTIVES: To determine (1) the optimal sites for mini-implant placement in the maxilla and the mandible based on dimensional mapping of the interradicular spaces and cortical bone thickness and (2) The effect of age and sex on the studied anatomic measurements. MATERIAL AND METHODS: The cone beam computed tomography images of 100 patients (46 males, 54 females) divided into two age groups (13-18 years), and (19-27 years) were used. The following interradicular measurements were performed: (1) Buccolingual bone thickness; (2) Mesiodistal spaces both buccally and palatally/lingually; and (3) Buccal and palatal/lingual cortical thicknesses. RESULTS: In the maxilla, the highest buccolingual thickness existed between first and second molars; the highest mesiodistal buccal/palatal distances were between the second premolar and the first molar. The highest buccal cortical thickness was between the first and second premolars. The highest palatal cortical thickness was between central and lateral incisors. In the mandible, the highest buccolingual and buccal cortical thicknesses were between the first and second molars. The highest mesiodistal buccal distance was between the second premolar and the first molar. The highest mesiodistal lingual distance was between the first and second premolars. The highest lingual cortical thickness was between the canine and the first premolar. The males and the older age group had significantly higher buccolingual, buccal, and palatal cortical thicknesses at specific sites and levels in the maxilla and the mandible. CONCLUSIONS: A clinical guideline for optimal sites for mini-implant placement is suggested. Sex and age affected the anatomic measurements in certain areas in the maxilla and the mandible. PMID- 20578868 TI - Evidence-based orthodontics. Current statistical trends in published articles in one journal. AB - OBJECTIVE: To ascertain the number, type, and overall usage of statistics in American Journal of Orthodontics and Dentofacial (AJODO) articles for 2008. These data were then compared to data from three previous years: 1975, 1985, and 2003. MATERIALS AND METHODS: The frequency and distribution of statistics used in the AJODO original articles for 2008 were dichotomized into those using statistics and those not using statistics. Statistical procedures were then broadly divided into descriptive statistics (mean, standard deviation, range, percentage) and inferential statistics (t-test, analysis of variance). Descriptive statistics were used to make comparisons. RESULTS: In 1975, 1985, 2003, and 2008, AJODO published 72, 87, 134, and 141 original articles, respectively. The percentage of original articles using statistics was 43.1% in 1975, 75.9% in 1985, 94.0% in 2003, and 92.9% in 2008; original articles using statistics stayed relatively the same from 2003 to 2008, with only a small 1.1% decrease. The percentage of articles using inferential statistical analyses was 23.7% in 1975, 74.2% in 1985, 92.9% in 2003, and 84.4% in 2008. CONCLUSIONS: Comparing AJODO publications in 2003 and 2008, there was an 8.5% increase in the use of descriptive articles (from 7.1% to 15.6%), and there was an 8.5% decrease in articles using inferential statistics (from 92.9% to 84.4%). PMID- 20578869 TI - Chin cup effects using two different force magnitudes in the management of Class III malocclusions. AB - OBJECTIVES: To evaluate the dental and skeletal effects of chin cup using two different force magnitudes in the management of Class III malocclusion cases. MATERIALS AND METHODS: Fifty growing patients (26 males and 24 females) with skeletal Class III and mandibular prognathism were selected. The patients were divided into three groups. Patients in group 1 (n = 20) were treated with a chin cup and occlusal bite plane using 600 g of force per side. Patients in group 2 (n = 20) were subjected to the same treatment as in group 1 but using 300 g of force per side. In group 3 (n = 10) no treatment was performed. For all patients, lateral cephalograms were taken before treatment and after 1 year. Cephalograms were traced and analyzed. The collected data were analyzed statistically using one-way analysis of variance and the Tukey test. RESULTS: In the treatment groups, the SNB angle and ramus height decreased significantly. The ANB angle, Wits appraisal, anterior facial height, mandibular plane angle, and retroclination of the mandibular incisors were significantly increased in comparison to the control group. Utilization of either force showed no significant differences, except that the reduction in the ramus height was significantly greater with the use of higher force. CONCLUSIONS: The use of a chin cup improved the maxillomandibular base relationship in growing patients with Class III malocclusion but with little skeletal effect. The utilization of either force had the same effects, except that the higher force had a more pronounced effect in reduction of ramus height. PMID- 20578870 TI - Shear bond strength of brackets bonded with hydrophilic and hydrophobic bond systems under contamination. AB - OBJECTIVE: To compare, in vitro, the shear bond strength (SBS) of two bond systems: Transbond XT/XT primer (TXT/XT) and Transbond Plus Color Change/Transbond Self Etching Primer (TPCC/TSEP). MATERIALS AND METHODS: Each system was examined under four enamel surface conditions (dry, water, saliva, and blood), and 160 bovine teeth were divided into eight groups of 20 according to enamel surface condition. Group 1 used TPCC/TSEP and Group 2 used TXT/XT under dry conditions; Group 3 used TPCC/TSEP and Group 4 used TXT/XT with water; Group 5 used TPCC/TSEP and Group 6 used TXT/XT under saliva; and Group 7 used TPCC/TSEP and Group 8 used TXT/XT with blood. Brackets were bonded, and the samples were thermocycled 500 times between 5 degrees C and 55 degrees C; they were then submitted to a shear bond test with a universal testing machine with a 50 kgf load cell at 5 mm/min. RESULTS: Although water and saliva affected TXT/XT more than they affected TPCC/TSEP, there were no significant differences among the groups (Groups 3 and 4: P = .940; Groups 3 and 5 and Groups 4 and 6: P = 1.000; Groups 3 and 6: P = .988; Groups 4 and 5: P = .690; and Groups 5 and 6: P = .861). CONCLUSIONS: The presence of blood resulted in the lowest SBS from both bond systems, but especially from TXT/XT. TPCC/TSEP resulted in a higher SBS than TXT/XT under all conditions except the dry enamel surface. PMID- 20578871 TI - Low-level laser therapy effects in traumatized permanent teeth with extrusive luxation in an orthodontic patient. AB - The aim of this case report was to present and evaluate the effect of low-level laser therapy on traumatized permanent teeth with extrusive luxation in an orthodontic patient. The treatment and follow-up evaluation of two orally luxated maxillary permanent central incisors in a 19-year-old man is described. Detailed anamnesis was taken, and extraoral, intraoral, radiographic examinations and electrical and thermal pulpal tests were performed to determine the type of the luxation and the further treatment protocol. Teeth were splinted with composite resin, and antibiotic therapy was prescribed. Low-level laser therapy was applied for 25 sessions. No root canal treatment was applied to the teeth. Continuation of the orthodontic treatment was restarted after 6 months. No sign of clinical or radiographic pathology was detected after 2 years from the end of the treatment. Teeth were identified healthy and sound without any root canal intervention. Treatments with low-level laser applications may be evaluated as noninvasive alternative treatment options in comparison with endodontic treatment for teeth with extrusive luxation more than 2 mm, especially for those who have orthodontic treatment needs. PMID- 20578872 TI - Anomaly of cervical vertebrae found on orthodontic examination: 8-year-old boy with cleft lip and palate diagnosed with Klippel-Feil syndrome. AB - We incidentally encountered an anomaly of the cervical vertebrae during orthodontic examination of an 8-year-old boy with cleft lip and palate. Klippel Feil syndrome was diagnosed by the orthopedic specialist to whom he had been referred for detailed examination. This case report shows the results of axial multislice-helical computed tomography with three-dimensional reconstructions of the cervical vertebrae. Furthermore, we evaluated the frequency of congenital anomalies on lateral cephalogram in patients with cleft lip and palate or cleft palate and non-cleft controls from among all patients in our orthodontic clinic. PMID- 20578873 TI - The influence of malocclusion on masticatory performance. A systematic review. AB - OBJECTIVE: To systematically review the relationship between malocclusions and masticatory performance. In addition, we will perform a qualitative analysis of the methodological soundness of the studies. MATERIALS AND METHODS: A literature survey was done by applying the Medline database ( www.ncbi.nim.nih.gov ) in the period from January 1965 to June 2009, using the "Medical Subject Headings" term malocclusion crossed with various combinations of the following terms: masticatory performance, masticatory efficiency, and chewing efficiency. The articles were separated into two main topics: (1) the influence of malocclusion treatment (orthognathic surgery) and (2) the influence of malocclusion type and severity. RESULTS: The search strategy used identified 78 articles. After selection according to the inclusion/exclusion criteria, 12 articles qualified for the final analysis. The research quality and methodological soundness were high in one study, medium in 10 studies, and low in one study. The most serious shortcomings comprised the clinical trials and controlled clinical trials designs with small sample sizes and inadequate description of selection criteria. Lack of method error analysis and the absence of blinding in measurements were other examples of shortcomings. CONCLUSIONS: Malocclusions cause decreased masticatory performance, especially as it relates to reduced occlusal contacts area. The influence of malocclusion treatment (orthognathic surgery) on masticatory performance is only measurable 5 years after treatment. PMID- 20578874 TI - Serologic assays specific to immunoglobulin M antibodies against hepatitis E virus: pangenotypic evaluation of performances. AB - Six immunoassays for detecting immunoglobulin M antibodies to hepatitis E virus were evaluated. Serum samples representing acute infection by each of the 4 viral genotypes as well as nonacute hepatitis E virus infection constituted the test panels. Diagnostic sensitivities and specificities as well as interassay agreement varied widely. Analytical sensitivity limits also were determined and were found to be particularly disparate. PMID- 20578875 TI - Effectiveness of adolescent and adult tetanus, reduced-dose diphtheria, and acellular pertussis vaccine against pertussis. AB - BACKGROUND: Pertussis is among the most poorly controlled bacterial vaccine preventable diseases in the United States. In 2006, a tetanus, reduced-dose diphtheria, and acellular pertussis (Tdap) booster was recommended for adolescents and adults. Tdap vaccines were licensed on the basis of antibody response without vaccine effectiveness data. METHODS: From 30 September 2007 through 19 December 2007, a pertussis outbreak occurred at a nursery through twelfth grade school on St. Croix, US Virgin Islands. We screened all students for cough and collected clinical history, including Tdap receipt. Coughing students were offered diagnostic testing. We defined clinical case patients as students with cough 14 days in duration plus either whoop, paroxysms, or post tussive vomiting, and we defined confirmed case patients as students with any cough with isolation of Bordetella pertussis or those with clinical cases and polymerase chain reaction or serological evidence of pertussis; other clinical cases were classified as probable. RESULTS: There were 51 confirmed or probable cases among 499 students (attack rate, 10%). Disease clustered in grades 6-12, with a peak attack rate of 38% among 10th graders. Of 266 students aged 11 years with complete data, 31 (12%) had received Tdap. Forty-one unvaccinated students (18%) had confirmed or probable pertussis, compared with 2 (6%) of the vaccinated students (relative risk, 2.9); vaccine effectiveness was 65.6% (95% confidence interval, -35.8% to 91.3%; P = .092). CONCLUSIONS: This first evaluation of Tdap vaccine effectiveness in the outbreak setting suggests that Tdap provides protection against pertussis. Increased coverage is needed to realize the full benefit of the vaccine program. Serological testing was an important tool for case identification and should be considered for inclusion in the Council of State and Territorial Epidemiologists case definition. PMID- 20578876 TI - Increased serum iron levels and infectious complications after liver transplantation. AB - BACKGROUND: Elevated serum iron levels have been associated with infectious outcomes in various patient populations but, to our knowledge, have never been studied after liver transplantation. METHODS: The relationship between serum iron levels and infectious outcomes after liver transplantation was evaluated in a nested case-control study using prospectively collected data and serum samples. Unadjusted and adjusted hazard ratios were calculated for each iron marker predictor variable (iron level, unsaturated iron-binding capacity, total iron binding capacity, transferrin saturation, and ferritin level) and time to development of each of 6 outcomes (cytomegalovirus [CMV] disease, invasive fungal infection, bacteremia, invasive fungal infection or bacteremia, any infection, and 1-year mortality rate). RESULTS: Serum measurements (n = 109) corresponding to increased levels of serum iron were independently associated with an increased risk of any infection and death. After adjusting for the number of red blood cell transfusions, donor CMV-seropositive status, and fungal colonization, ferritin level was independently associated with the development of any infection (hazard ratio, 1.09; 95% confidence interval, 1.04-1.14). After adjusting for the number of red blood cell transfusions, development of CMV disease, and administration of intravenous steroids for treatment of rejection, ferritin level was also was independently associated with death (hazard ratio, 1.11; 95% confidence interval, 1.04-1.18). Similar results were found for unsaturated iron binding capacity for the same 2 outcomes. CONCLUSIONS: A better understanding of iron metabolism and its relationship to infection could help guide future infection prognosis, prevention, and management efforts in this high-risk population. PMID- 20578877 TI - Switching from efavirenz to nevirapine. PMID- 20578880 TI - Diversity and distribution of Braconidae, a family of parasitoid wasps in the central European peatbogs of South Bohemia, Czech Republic. AB - An ecological overview of seven years investigation of Braconidae, a family of parasitoid wasps (Hymenoptera: Ichneumonoidea) and a tyrpho-classification of parasitoids in peatbog areas of South Bohemia, Czech Republic are given. A total of 350 species were recorded in investigated sites, but only five tyrphobionts (1.4%) are proposed: Microchelonus basalis, Microchelonus koponeni, Coloneura ate, Coloneura danica and Myiocephalus niger. All of these species have a boreal alpine distribution that, in Central Europe, is associated only with peatbogs. Tyrphophilous behaviour is seen in at least four (1.1%) species: Microchelonus pedator, Microchelonus subpedator, Microchelonus karadagi and Microchelonus gravenhorstii; however, a number of other braconids prefer peatbogs because they were more frequently encountered within, rather than outside, the bog habitat. The rest of the braconids (342 species, 97.5%) are tyrphoneutrals, many of them being eurytopic components of various habitats throughout their current ranges. Lists of tyrphobiontic braconids and a brief commentary on species composition, distributional picture of actual ranges, and parasitoid association to bog landscape are provided. Being true refugial habitats for populations in an ever changing world, peatbogs play a significant role in harboring insect communities. PMID- 20578879 TI - The influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process. AB - PURPOSE: To study the influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of solid lipid nanoparticles (SLN) prepared by the double emulsion method. METHODS: Stearic acid (SA), octadecyl alcohol (OA), cetyl palmitate (CP), glyceryl monostearate (GM), glyceryl palmitostearate (GP), glyceryl tripalmitate (GT), and glyceryl behenate (GB) were selected as the representatives of different kinds of lipids, insulin and thymopentin (TP5) were selected as the model protein drugs. Before preparation, the contact angles between water and lipids were determined to investigate their hydrophobicity. The influence of lipid hydrophobicity or lipid solution viscosity on the preparation of primary emulsion, double emulsion, and SLN were studied by evaluating the particle size, state, and stability of the systems. CP-SLN, GT-SLN, and GP-SLN were selected to be loaded with insulin and TP5 for the in vitro release and in vivo absorption examination. After oral administration to diabetic rats, the pharmacological availability (PA) of insulin-CP-SLN, insulin-GP-SLN, and insulin GT-SLN were determined. RESULTS: The hydrophobicity order of the lipids was GM=3 loose stools in 24-hours, lasting >1 day, or restricting daily activities) was 7.7%. This proportion was consistent among the respondents who were first asked about a 7-day recall period (n=1436) and those asked only about symptoms in the past month (n=2132). Extrapolation from the reported 7-day prevalence of 3.1% to an annual rate of 1.6 episodes per person, however, was almost twice the rate of episodes estimated when extrapolating from the month recall period. Similar findings were found with acute gastroenteritis (acute diarrheal illness or vomiting without respiratory symptoms). CONCLUSIONS: First asking respondents about a 7-day recall period did not affect the prevalence of acute gastroenteritis reported for a 1-month recall period. Recall period length did, however, have a major impact on estimates of acute gastroenteritis. Retrospective studies using different recall periods may not be comparable. PMID- 20578915 TI - Antimicrobial-resistant enterococci in animals and meat: a human health hazard? AB - Enterococcus faecium and Enterococcus faecalis belong to the gastrointestinal flora of humans and animals. Although normally regarded harmless commensals, enterococci may cause a range of different infections in humans, including urinary tract infections, sepsis, and endocarditis. The use of avoparcin, gentamicin, and virginiamycin for growth promotion and therapy in food animals has lead to the emergence of vancomycin- and gentamicin-resistant enterococci and quinupristin/dalfopristin-resistant E. faecium in animals and meat. This implies a potential risk for transfer of resistance genes or resistant bacteria from food animals to humans. The genes encoding resistance to vancomycin, gentamicin, and quinupristin/dalfopristin have been found in E. faecium of human and animal origin; meanwhile, certain clones of E. faecium are found more frequently in samples from human patients, while other clones predominate in certain animal species. This may suggest that antimicrobial-resistant E. faecium from animals could be regarded less hazardous to humans; however, due to their excellent ability to acquire and transfer resistance genes, E. faecium of animal origin may act as donors of antimicrobial resistance genes for other more virulent enterococci. For E. faecalis, the situation appears different, as similar clones of, for example, vancomycin- and gentamicin-resistant E. faecalis have been obtained from animals and from human patients. Continuous surveillance of antimicrobial resistance in enterococci from humans and animals is essential to follow trends and detect emerging resistance. PMID- 20578916 TI - Transferable class 1 and 2 integrons in Escherichia coli and Salmonella enterica isolates of human and animal origin in Lithuania. AB - Antibiotic-resistant Escherichia coli (n = 191) and Salmonella enterica (n = 87) isolates of human and animal origin obtained in Lithuania during 2005-2008 were characterized for the presence and diversity of class 1 and 2 integrons. E. coli isolates were obtained from patients with urinary tract infections (UTIs) (n = 59) and both healthy and diseased farm animals, including poultry (n = 54), swine (n = 35), and cattle (n = 43). Isolates of non-typhoidal S. enterica were recovered from salmonellosis patients (n = 37) and healthy animals, including poultry (n = 31) and swine (n = 19). The presence of integrons, their gene cassette structure, and genome location were investigated by polymerase chain reaction, restriction fragment-length polymorphism, DNA sequencing, Southern blot hybridization, and conjugation experiments. Forty percent of the E. coli and 11% of the S. enterica isolates carried class 1 integrons, whereas class 2 integrons were found in E. coli isolates (9%) only. The incidence of integrons in human UTIs and cattle isolates was most frequent (p < 0.01). A total of 23 different gene cassettes within 15 different variable regions were observed. Seven different integron types, all of them transferable by conjugation, were common for isolates from human infections and for one or more groups of animal isolates. The most prevalent integron types contained arrays dfrA1-aadA1 (36%), dfrA17 aadA5 (23%), and dfrA1-sat1-aadA1 (78%). Two E. coli isolates from humans with UTIs harbored class 1 integron on conjugative plasmid with the novel array type of 4800 bp/dfrA17-aadA5Delta-IS26-DeltaintI1-aadB-aadA1-cmlA residing on the Tn21 like transposon. Three S. enterica isolates from swine contained class 1 integron with the newly observed array type of 1800 bp/aadA7-aadA7. Integrons of 10 different types of both classes were located on transferable plasmids in E. coli and S. enterica. Our study demonstrated the existence of a considerable and common pool of transferable integrons in E. coli and S. enterica present in clinical and livestock environment in Lithuania. PMID- 20578918 TI - Fluoroscopic organ and tissue-specific radiation exposure by sex and body mass index during ureteroscopy. AB - INTRODUCTION: Although radiation exposure from CT and plain film imaging has been characterized, the radiation received by patients during modern-era fluoroscopy has not been well described. The purposes of this study were to measure absolute organ and tissue-specific radiation doses during ureteroscopy and to determine the influence of body mass index (BMI) and sex on these doses. MATERIALS AND METHODS: Eight cadavers underwent a simulated left ureteroscopy. Using a modern C arm with automatic exposure control settings, thermoluminescent dosimeters were exposed for a fluoroscopy time of 145 seconds (mean time of clinical ureteroscopies from 2006 to 2008). Total tissue exposures were compared by BMI and between sexes using the Wilcoxon signed ranks test and the Mann-Whitney test with p < 0.05 considered significant. RESULTS: Among all cadavers, radiation doses were significantly lower in all contralateral organs excluding the gonad (p < 0.012). Doses were similar bilaterally in the gonad in cadavers with BMI <30, and in all organs in cadavers with BMI >30 (p > 0.05). There were significantly higher mean bilateral gonadal doses in female cadavers (3.4 mGy left and 1.9 mGy right) compared with male cadavers (0.36 mGy left and 0.39 mGy right). The highest cancer risk increase was seen at the posterior skin equivalent to 104 additional cancers per 100,000 patients. CONCLUSION: Contralateral doses were lower for all organs except the gonad when the BMI was <30. In contrast, when the BMI was >30, there was no difference in radiation dose delivered to the ipsilateral and contralateral organs. Gonadal doses were significantly higher in female cadavers. Modern-era fluoroscopy remains a significant source of radiation exposure and steps should be taken to minimize exposure during ureteroscopy. PMID- 20578919 TI - Inpatient mortality and length of stay comparison of percutaneous endoscopic gastrostomy and percutaneous endoscopic gastrojejunostomy. AB - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic gastrojejunostomy (PEGJ) are endoscopic procedures often performed by surgeons. No recent population-based study has compared inpatient mortality or length of stay between patients who undergo PEG or PEGJ placement during their hospitalization. METHODS: Patients undergoing inpatient PEG or PEGJ placement and who were at least 18 years old were identified from the 2006 Nationwide Inpatient Sample (NIS) database. Baseline characteristics of each group were compared, and outcomes of risk-adjusted inpatient mortality and length of stay were determined. Means were compared from using a complex sample t-test, and proportions were compared from using a complex sample chi-square test, with an alpha level of 0.05 for significance. Bivariate logistic regression was used to evaluate PEG or PEGJ placement as a risk factor for mortality. RESULTS: In the 2006 NIS, 187,597 discharges were identified, during which a PEG or PEGJ was placed. Ninety-six percent (179,587) of patients underwent PEG placement, and 4% (8010) had PEGJ tubes placed. Fifty-one percent were men, with the mean age for PEG and PEGJ placement of 71.3 +/- 0.3 (mean +/- standard error) and 64.8 +/- 0.8 years (P < 0.05). In the PEG group, 86% of admissions were nonelective, compared to 79% in the PEGJ group (P < 0.05). The primary discharge diagnoses for both groups of patients included acute cerebrovascular disease, aspiration pneumonitis, septicemia, respiratory failure, and intracranial injury. PEG patients had a higher cumulative incidence of congestive heart failure, chronic lung disease, and diabetes. Crude in-hospital mortality for death was 11% for both PEG and PEGJ patients. No difference in mortality was observed in risk-adjusted analyses accounting for patient severity. Mean length of stay was similar for both groups (PEG 20.9 +/- 0.4 days; PEGJ 22.5 +/- 1.1 days). Neither PEG nor PEGJ was identified as a risk factor for inpatient mortality. CONCLUSIONS: Comparative analyses of patients undergoing PEG versus PEGJ revealed no detectable difference between inpatient mortality and hospital length of stay in this large observational study. Both procedures can be performed safely in high-risk populations, with no increased mortality or length of stay incurred by jejunal feeding access. However, further analysis is required to compare more specific short-term outcomes between these populations as well as their respective cost effectiveness. PMID- 20578920 TI - Salpingoscopy during laparoscopy using a small-caliber hysteroscope introduced through an accessory trocar. AB - Salpingoscopy is an endoscopic technique that allows the direct visualization of the tubal mucosa. The status of the tubal mucosa is the best prognostic factor when evaluating patients with tubal infertility. Salpingoscopy, performed during laparoscopy, has not reached wide acceptance due the costly, non-user-friendly, dedicated instrumentation needed. In this article, a simplified technique to perform salpingoscopy at the time of laparoscopy is reported, using a standard 2.9-mm diagnostic hysteroscope, with a 3.7-mm single-flow diagnostic sheath, introduced through an accessory port. Salpingoscopy, with this new technique, was performed in 13 patients with tubal infertility. The tubes were successfully cannulated in all patients, for a total of 24 tubes evaluated (2 patients had a single tube). Salpingoneostomy and salpingoovarolysis were completed after salpingoscopy only when the tubal mucosa was normal. In 1 patient with severe tubal damage, salpingectomy of the single remaining tube was performed. Salpingoscopy added a mean of 15 minutes to surgical time. Intrauterine pregnancies were obtained, after salpingoneostomy, fimbrioplasty, or adhesiolysis, in 5 of 12 patients (42%), with a mean follow-up of 9 months. The simplified technique of salpingoscopy, with a diagnostic hysteroscope introduced through an accessory trocar at the time of laparoscopy, adds important information on the reproductive potential of patients with tubal disease. PMID- 20578921 TI - Laparoscopic surgery in the elderly: personal experience in 141 cases. AB - INTRODUCTION: As life expectancy increases, the number of elderly patients presenting with surgically correctable diseases will rise as well. For advantages, which are well recognized in young patients, laparoscopic surgery has been proposed also for older patients. Because of underlying chronic diseases, however, elderly patients have been considered at high risk for the laparoscopic approach. Several studies have pointed out the risks related to cardiac, respiratory, or general comorbidities when elderly patients are proposed for laparoscopic treatment of their surgical disease. PATIENTS AND METHODS: In this study, we reported our experience in 141 patients older than 65 years who were submitted to laparoscopic procedures for several indications. According to American Society of Anesthesiologists (ASA) score, patients were classified as ASA I in 70.9% of cases, ASA II in 27.6%, and ASA III in 1%. RESULTS: No mortality has been reported. Conversion rate was 5.3% for bleeding in 4 cases or intraoperative hypotension in 2 cases. Mean hospital stay was 5 days. Postoperative complication was reported in 1 case and consisted of a hearth attack. CONCLUSIONS: Laparoscopic surgery in the elderly is a safe procedure, if preoperative selection of the patients is accomplished. An experienced surgical team and multidisciplinary approach are mandatory. PMID- 20578922 TI - Laparoscopic cholecystectomy under spinal versus general anesthesia: a prospective, randomized study. AB - BACKGROUND: For laparoscopic cholecystectomy (LC), the use of spinal anesthesia may offer several advantages over general anesthesia. The aim of this prospective, randomized study was to compare the surgical outcome of LC performed under general anesthesia to that of LC performed under spinal anesthesia. METHODS: Sixty patients were randomly assigned to either the SALC (spinal anesthesia LC group, 30 patients) or GALC group (general anesthesia LC group, 30 patients). Intraoperative events related to spinal anesthesia, postoperative complications, and pain scores were recorded. Patient satisfaction as to the anesthetic technique received was assessed 2 weeks postoperatively by direct patient questionnaire. RESULTS: In both groups, all procedures were completed laparoscopically. In the SALC group, all procedures were completed under spinal anesthesia and there were no anesthetic conversions. There was no statistically significant difference in the mean operative time between both groups. For the first 2 and 4 hours postoperatively, the mean pain score of the SALC group was statistically significantly lower than that of the GALC group. For the first 24 hours postoperatively, the mean number of analgesic ampoules/patient was statistically significantly lower in the SALC group. In the SALC group, 28 patients (93.3%) considered the technique "very well," compared with 30 patients (100%) in the GALC group. The difference in the overall patient satisfaction scores between both studied groups was not statistically significant. CONCLUSIONS: LC performed under spinal anesthesia is feasible, safe, and is associated with significantly less early postoperative pain, compared to that performed under general anesthesia. PMID- 20578923 TI - Peritoneal transforming growth factor beta-1 expression during prolonged laparoscopic procedures. AB - BACKGROUND: Laparoscopic surgery may affect peritoneal physiology. Short-term laparoscopic surgery does not affect peritoneal transforming growth factor beta (TGF-b1) expression. The current study was conducted to evaluate the hypothesis that prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression. STUDY DESIGN: In the first study, 24 patients scheduled for a right colonic resection were enrolled in the trial. Twelve underwent conventional surgery (CCR) and 12 were operated on laparoscopically (LCR). In the second study, 12 patients undergoing laparoscopic gastric bypass (LGB) surgery for morbid obesity were included. Biopsies of the parietal peritoneum were taken at standardized moments during the procedures. Tissue concentrations of active and total TGF-b1 were measured by using enzyme-linked immunosorbent assays. RESULTS: During the LCR, there was a significant increase in peritoneal active TGF-b1 levels (P < 0.05). A similar, but not significant, trend was observed during the CCR. A similar pattern was seen in the total TGF-b1 concentrations during both procedures. The LGB procedure did not affect peritoneal active or total TGF-b1 concentrations. During the procedure, both the active and total TGF-b1 levels were significantly higher in the LCR, when compared to the LGB, group (P < 0.05). CONCLUSIONS: Prolonged laparoscopic surgery may affect peritoneal TGF-b1 expression, depending on the procedure performed. Considering the role of TGF-b1 in various biologic processes, including adhesiogenesis and oncology, these results may have clinical consequences. PMID- 20578924 TI - The use of tacker and arthroscopy cannules in SILS cholecystectomy. AB - BACKGROUND: The invasiveness of laparoscopic cholecystectomy was further minimized by reducing the number of incisions with the introduction of single incision laparoscopic surgery (SILS) cholecystectomy. In order to solve the challenges posed by SILS cholecystectomy, an increasing number of techniques have been reported with the advent of new surgical instruments and refinements to existing technology. We describe, in this article, two new techniques that utilize existing instrumentations: an access and a retraction technique. METHODS: A consecutive series of 23 selected patients with symptomatic cholelithiasis underwent SILS cholecystectomy from April 10, 2009 to August 12, 2009. The overall procedure was similar to SILS cholecystectomy described in the literature. Hovewer, the access technique, with small-size arthroscopy cannules, was used to overcome the technical difficulty resulting from the collision of large-size caps of the laparoscopy trocars, and the retraction technique with a tacker was used to suspend the fundus of the gallbladder without taking the risk of gallbladder perforation. RESULTS: All patients were female, and the mean age was 34 years (range, 27-65). The body mass index of all patients was below 30 kg/m(2). The use of arthroscopy cannules provided a wider range of movement, and the retraction of the gallbladder was achieved safely with the tacker. These techniques reduced the operative times considerably. CONCLUSIONS: Most of the challenges posed by SILS cholecystectomy can be easily solved with simple technical modifications. PMID- 20578925 TI - A novel combined laparoscopic-endoscopic cooperative approach for duodenal lesions. AB - PURPOSE: A surgical approach with minimal invasion and excellent outcome for removal of duodenal lesions, using laparoscopic-endoscopic cooperative surgery (LECS), was established. PATIENTS AND METHODS: Two patients underwent the resection of duodenal lesions with our novel LECS approach. Case 1 (age: 49 years; male) had a 20-mm 0-IIa-like lesion (group IV tumor on biopsy) in the duodenal bulb. LECS interventions, performed under general anesthesia, employed a total of four trocars. The extent of lesions was determined with the endoscopic submucosal dissection (ESD) technique. The affected duodenal wall was then perforated before a one fifth turn resection was performed to expose lesions of the whole layer. A tumor, confirmed under laparoscopy, was turned over toward the abdominal cavity to facilitate resection. Case 2 (age: 49 years; female) had 20 mm 0-IIc lesions (group III adenoma) located at the second portion of the duodenum. LECS procedures for duodenal resection were performed in a manner similar to case 1 . A total of five trocars were used. RESULTS: Histologic diagnosis of the tumor in case 1 was tubular adenoma with moderate atypia (size: 20 x 12 mm). As for case 2, histopathologic findings confirmed a tubular adenoma with moderate atypia (size: 18 x 18 mm) and an adenoma-negative surgical margin. The postoperative courses, in both cases, were uneventful. CONCLUSIONS: Although only 2 cases were surgically intervened with limited experience, the present novel LECS approach allowed a reliable, adequate resection of tumors located in the duodenum, with abbreviated operation times (156-179 versus 202-229 minutes), minimal bleeding, less postoperative stress imposed on the surgeons, and an uneventful postoperative course, compared to conventional surgical methods. PMID- 20578927 TI - A 1,536-well ultra-high-throughput siRNA screen to identify regulators of the Wnt/beta-catenin pathway. AB - High-throughput siRNA screens are now widely used for identifying novel drug targets and mapping disease pathways. Despite their popularity, there remain challenges related to data variability, primarily due to measurement errors, biological variance, uneven transfection efficiency, the efficacy of siRNA sequences, or off-target effects, and consequent high false discovery rates. Data variability can be reduced if siRNA screens are performed in replicate. Running a large-scale siRNA screen in replicate is difficult, however, because of the technical challenges related to automating complicated steps of siRNA transfection, often with multiplexed assay readouts, and controlling environmental humidity during long incubation periods. Small-molecule screens have greatly benefited in the past decade from assay miniaturization to high density plates such that 1,536-well nanoplate screenings are now a routine process, allowing fast, efficient, and affordable operations without compromising underlying biology or important assay characteristics. Here, we describe the development of a 1,536-well nanoplate siRNA transfection protocol that utilizes the instruments commonly found in small-molecule high throughput screening laboratories. This protocol was then successfully demonstrated in a triplicate large-scale siRNA screen for the identification of regulators of the Wnt/beta catenin pathway. PMID- 20578928 TI - An important new resource emerges for child and adolescent mental health. PMID- 20578929 TI - Effectiveness of medication combined with intensive behavioral intervention for reducing aggression in youth with autism spectrum disorder. AB - BACKGROUND: The use of antipsychotic medications to treat aggression in youths with autism spectrum disorders (ASD) is based on open-label trials and efficacy studies. There are no studies examining the combined effectiveness of antipsychotic medications and intensive behavioral intervention (IBI) to treat aggression in ASD. METHODS: Youths with ASD and aggressive behavior received IBI. Medication use remained stable during the study period and was coded into antipsychotic, mood-stabilizing, and nonstimulant attention-deficit/hyperactivity disorder (ADHD)/sleep medication classes. Analysis of covariance (ANCOVA) and survival analyses examined the effects of medication classes on the average number of aggressive behaviors and time to behavior plan success. RESULTS: Thirty two youths (mean age = 11.16, standard deviation [SD] = 3.31, range = 4-16 years, 75% male) with ASD received aggression reduction plans. Of these, 25 youths were taking at least one psychiatric medication (antipsychotic n = 18, mood stabilizing n = 10, and nonstimulant ADHD/sleep n = 12). Aggression dropped substantially following implementation of IBI (p < 0.001; d = 1.70). Antipsychotic medication use predicted significantly fewer sessions to achieve behavior plan success (chi(2)(1) = 5.67, p = 0.017; d = 0.93). No other medication classes influenced aggressive behavior (largest chi(2)(1) = 0.16, p = 0.694). CONCLUSIONS: Behavioral treatment combined with antipsychotic medication was the most effective approach to reducing aggressive behaviors in youths with ASD. Mood-stabilizing and nonstimulant ADHD/sleep medications did not contribute to aggression reduction. PMID- 20578930 TI - Sex differences in attentional performance and their modulation by methylphenidate in children with attention-deficit/hyperactivity disorder. AB - BACKGROUND: Still little is known about neuropsychological differences between boys and girls with attention-deficit/hyperactivity disorder (ADHD) and whether there are sex-specific differences in the modulation of attentional performance by methylphenidate (MPH). METHOD: In this study, 27 males and 27 females between 8-12 years old and with ADHD were investigated in a double-blind, placebo controlled trial on five computerized attention tests (0.25 vs. 0.5 mg/kg MPH as a single dose, versus placebo). RESULTS: Boys and girls with ADHD did not differ with respect to age, intelligence quotient (IQ), symptom severity, co-morbidity patterns, and ADHD subtype. However, ADHD boys were more impulsive on a sustained attention task, whereas girls with ADHD had more deficits on tasks measuring selective attention. Attentional performance increased differentially as a function of MPH dose, with some tasks showing linear improvement with higher dosage whereas more complex tasks in particular showed inverse U-shaped patterns of MPH effects. However, these effects were comparable between girls and boys. CONCLUSIONS: Our data suggest that there are some gender differences in attentional performance in subjects with ADHD in a clinical sample, even if symptom severity and co-morbidity are controlled; however, modulation of attention by MPH does not seem to differ between sexes. PMID- 20578931 TI - Dose-response characteristics in adolescents with attention-deficit/hyperactivity disorder treated with OROS methylphenidate in a 4-week, open-label, dose titration study. AB - OBJECTIVE: The aim of this study was to evaluate dose-response characteristics in adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with once-daily OROS methylphenidate (OROS MPH) during the 4-week, open-label, escalating dose-titration phase of a larger multisite, placebo-controlled trial. Patient factors such as age, height, weight, and baseline symptom severity were evaluated as predictors of selected dose, as was the degree of incremental response with each successive dose escalation. METHODS: Adolescents 13-18 years of age with ADHD underwent a 4-week, open-label, escalating dose-titration trial to determine the minimal effective dose (18, 36, 54, or 72 mg once daily) of OROS to be used in a multiphase, placebo-controlled study (NCT00249353). Both final absolute dose and mean weight-adjusted dose were used to assess predictors of response, using a one-way analysis of variance and regression analyses. RESULTS: The majority of subjects who did not respond at lower doses achieved response at each escalating dose level. Approximately two-thirds of subjects required a dose of 54 mg or greater to achieve improvement criteria. Minimal effective dose correlated modestly with baseline symptom severity. Age, height, and weight did not correlate with absolute dose and accounted for only a small percentage of variance in weight-based dose. Weight was not a major factor in predicting effective dose; however, using weight-adjusted rather than absolute dose proved slightly superior for modeling of adverse effects. CONCLUSIONS: Adolescents required, on average, a higher absolute dose but a lower weight-adjusted dose (mg/kg) of OROS) than was previously reported in children. There were few predictors of optimal dose of OROS other than baseline symptom severity. The increased percentage of adolescent responders at each dose level using this clinically driven approach to titration differs from recent findings from randomized forced dose titration studies in adults with ADHD. PMID- 20578932 TI - Factors associated with atomoxetine efficacy for treatment of attention deficit/hyperactivity disorder in children and adolescents. AB - OBJECTIVES: The aims of this study were to determine if relationships exist between the efficacy of atomoxetine for treatment of attention deficit/hyperactivity disorder (ADHD) and demographic characteristics, specific co-morbid diagnoses, subtype of ADHD, and/or additional use of a stimulant medication. METHOD: A retrospective chart review was performed using data from an institutional electronic medical record system. Children aged 5-17 years who were diagnosed with ADHD and prescribed atomoxetine were included; 432 study subjects were categorized as treatment success (TS), treatment failure (TF), or undetermined. Co-morbid diagnoses, demographic factors, subtype of ADHD, and additional use of stimulant medications were examined for association with TS. RESULTS: A total of 88 children were categorized as TS, 197 as TF, and 147 as undetermined. More subjects in the TS group were receiving stimulant medication in addition to the atomoxetine than in the TF group (p = 0.0319; 95% Wald confidence interval [CI], 1.064-3.972). There was no significant difference between groups for any demographic characteristic, the presence of any co-morbid diagnosis, or type of ADHD. In particular, the presence of anxiety or depression was not associated with a response to atomoxetine. CONCLUSION: Children who were prescribed a stimulant medication in addition to atomoxetine had better outcomes in treating ADHD than those receiving only atomoxetine. PMID- 20578933 TI - Clinical experience using electroconvulsive therapy in adolescents with schizophrenia spectrum disorders. AB - OBJECTIVES: The aim of this study was to evaluate the effectiveness and safety of electroconvulsive therapy (ECT) in adolescent patients diagnosed with schizophrenia spectrum disorders (SSD). METHODS: All patients diagnosed with SSD who received ECT in the Child and Adolescent Psychiatry and Psychology Department in a general hospital in Barcelona, Spain, from January, 2003, to December, 2007, were identified retrospectively. As part of the usual evaluation protocol, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scales were administered before ECT, after the acute ECT phase (CGI), and at 6 months from baseline. Data related to characteristics of these patients such as demographics, pharmacological treatment, ECT parameters, and side effects were registered. RESULTS: Thirteen cases, ages 13-17 (mean age, 16.6 +/- 1.2 years), were included. Compared to pre-ECT scores, mean PANSS decreased significantly at 6-month assessment (t = 3.58, p = 0.004). Clinical response (20% or greater reduction in PANSS total scores at the 6-month end point) was achieved in 54% of patients. A significant improvement of mean CGI score was observed after the acute ECT phase (t = 11.88, p < 0.001) and at 6-month assessment (t = 12.48, p < 0.001). There were no severe incidents related to any session during the acute ECT phase, although 1 patient experienced a tardive seizure during the continuation ECT. CONCLUSIONS: Our clinical experience supports the assertion that ECT is a safe and effective treatment for SSD in adolescent patients. PMID- 20578934 TI - Anxiety as a predictor of treatment outcome in children and adolescents with depression. AB - OBJECTIVE: The aim of this study was to examine the impact of co-morbid illnesses on treatment outcomes in depressed children and adolescents aged 7-17 who were treated with fluoxetine. METHOD: This data set was drawn from two large clinical trials involving children and adolescents with depression. Subjects with a diagnosis of major depressive disorder and depressive symptoms of at least moderate severity as defined by a Children's Depression Rating Score, Revised (CDRS-R) total score >or=40 and a Clinical Global Impressions-Severity (CGI-S) rating >or=4 were included. Subjects were randomized to receive fluoxetine or placebo over an 8-week period. Predictor analyses examining two primary outcomes were conducted: (1) Response based on Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2, and (2) remission based on CDRS-R score of T (p.N198I), c.625+19 C>T, c.1062 C>T (N354N), and c.1224 G>A (p.T408T) in the G6PT gene. RNA studies were performed for c.1124 2del and c.625+19 C>T. The c.1124-1del2 acceptor splicing mutation showed skipping of 31 nucleotides of exon 9 due to the activation of a downstream cryptic acceptor splice site in 1154-1155 nucleotide positions, resulting in a downstream stop codon at aa position 402. RNA analysis of c.625+19 C>T variation showed a small amount of alternative splicing with skipping of exon 4, resulting in a stop codon at aa position 211. Our cases present most of features of the severe form of disease, including early onset with chronic neutropenia, frequent infections, and inflammatory bowel disease. Our results suggest a founder effect for glycogen storage disease type Ib that facilitates diagnosis using mutation analysis, sparing patients from liver biopsy. DNA-based diagnosis will enable us to make accurate determination of carrier status and prenatal diagnosis, thus improving genetic counseling. PMID- 20578943 TI - Prenatal diagnosis for a novel splice mutation of PHEX gene in a large Han Chinese family affected with X-linked hypophosphatemic rickets. AB - BACKGROUND: X-linked hypophosphatemia (XLH) is the most common form of heritable rickets characterized by X-linked dominant inheritance, renal phosphate wasting, hypophosphatemia, and defective bone mineralization. Inactivating mutations of the PHEX gene located at Xp22.1 have been linked with this disease. Ethnic distribution of such mutations seems widespread but only a few mutations in the Chinese population have been reported to date. MATERIALS AND METHODS: We report on a large Han Chinese family affected with XLH rickets, which included 13 patients from four generations. Polymerase chain reaction and direct sequencing were performed for all exons and intron-exon boundaries of the PHEX gene. The effect of nucleotide changes was analyzed using bioinformatic software. Prenatal diagnosis was performed on umbilical cord blood at the 20th gestational week. RESULTS: A novel G-->A splice mutation in intron 7 (c.849+1G>A) was identified in all patients from the family. As confirmed by reverse-transcription (RT) polymerase chain reaction (PCR), the mutation has rendered loss of a normal splice donor site (c.849+1G) while activating a cryptic one at c.849+519G, which resulted in addition of 518 nucleotides to the mature RNA. Prenatal diagnosis had excluded the fetus for carrying the same mutation. A healthy boy was born later. CONCLUSIONS: A novel splice mutation c.849+1G>A in the PHEX gene is responsible for XLH in the studied family. Further studies may enhance our understanding of the role of this mutation in the pathogenesis of XLH. PMID- 20578945 TI - Very low frequencies of Toll-like receptor 2 supposed-2029T and 2258A (RS5743708) mutant alleles in southern Brazilian critically ill patients: would it be a lack of worldwide-accepted clinical applications of Toll-like receptor 2 variants? AB - Toll-like receptor 2 (TLR2) is a recognition receptor for the widest repertoire of pathogen-associated molecular patterns. Two polymorphisms of TLR2 could be linked to reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and to increased risk of infection (supposed-2029C>T and 2258G>A). We investigated the supposed-2029C>T and 2258G>A TLR2 polymorphisms in 422 critically ill patients of European origin from southern Brazil (295 with sepsis and 127 without sepsis) and reviewed 33 studies on these polymorphisms, conducting a quality assessment with a score system. Among our patients we found only one heterozygote (1/422) for the supposed-2029C>T and none for the 2258G>A (0/422) single nucleotide polymorphism (SNP). We were unable to find a clinical application of supposed-2029T and 2258A allele analyses in our southern Brazilian population. Our review detected that current TLR2 SNP assays had very controversial and contradictory results derived from reports with a variety of investigation quality criteria. We suggest that, if analyzed alone, the supposed 2029C>T and 2258G>A TLR2 SNP are not good candidates for genetic markers in studies that search for direct or indirect clinical applications between genotype and phenotype. Future efforts to improve the knowledge and to provide other simultaneous genetic markers might reveal a more effective TLR2 effect on the susceptibility to infectious diseases. PMID- 20578946 TI - PTPN11 and KRAS gene analysis in patients with Noonan and Noonan-like syndromes. AB - Noonan and Noonan-like syndromes are disorders of dysregulation of the rat sarcoma viral oncogene homolog (RAS)-mitogen-activated protein kinase signaling pathway. In Noonan syndrome (NS), four genes of this pathway (PTPN11, SOS1, RAF1, and KRAS) are responsible for roughly 70% of the cases. We analyzed PTPN11 and KRAS genes by bidirectional sequencing in 95 probands with NS and 29 with Noonan like syndromes, including previously reported patients already screened for PTPN11 gene mutations. In the new patients with NS, 20/46 (43%) showed a PTPN11 gene mutation, two of them novel. In our total cohort, patients with NS and a PTPN11 mutation presented significantly higher prevalence of short stature (p = 0.03) and pulmonary valve stenosis (p = 0.01), and lower prevalence of hypertrophic cardiomyopathy (p = 0.01). Only a single gene alteration, of uncertain role, was found in the KRAS gene in an NS patient also presenting a PTPN11 gene mutation. We further analyzed the influence in clinical variability of three frequent polymorphisms found in the KRAS gene and no statistically significant difference was observed among the frequency of clinical findings regarding the studied polymorphisms. PMID- 20578947 TI - The genetic background difference between diabetic patients with and without nephropathy in a Taiwanese population by linkage disequilibrium mapping using 382 autosomal STR markers. AB - The genome-wide linkage disequilibrium screening for loci associated with genetic difference between diabetic patients with and without nephropathy was conducted employing 382 autosomal STR markers involving 185 diabetic subjects. Among them, 25 STR markers showed evidence for nominal association with a difference between the two diabetic groups. To investigate the reliability of the association result, the E2a/Pbx1-activated gene in pre-B cells 1 (EB-1) gene was selected from 267 diabetic subjects for single-nucleotide polymorphism genotyping because its genomic region encircles the significant STR marker D12S346. It is clear that some single-nucleotide polymorphisms and haplotypes of the EB-1 gene are associated with genetic difference between diabetic patients with and without nephropathy. This study further indicates that diabetic nephropathy is indeed a genetically heterogeneous group of diseases with similar clinical phenotypes. PMID- 20578948 TI - Development of a ribosomal DNA ITS2 marker for the identification of the thrips, Scirtothrips dorsalis. AB - The thrips Scirtothrips dorsalis Hood (Thysanoptera: Thripidae) is an invasive pest that poses a significant economical threat to U.S. agriculture and trade. In this study, DNA sequence data and polymerase chain reaction (PCR) were utilized to develop a molecular diagnostic marker for S. dorsalis. The DNA sequence variation from the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA (rDNA) was analyzed from various thrips species, including S. dorsalis. A primer set and polymerase chain reaction cycling parameters were designed for the amplification of a single marker fragment of S. dorsalis ITS2 rDNA. Specificity tests performed on ten thrips species, efficacy tests performed on fifteen S. dorsalis populations, and tests on primer sensitivity and robustness all demonstrated the diagnostic utility of this marker. This diagnostic PCR assay provides a quick, simple, and reliable molecular technique to be used in the identification of S. dorsalis. PMID- 20578949 TI - Observations on hilltopping in thick-headed flies (Diptera: Conopidae). AB - Direct observations of hilltopping behaviour in the thick-headed flies (Diptera: Conopidae) have only been mentioned once in the literature. Hilltop collecting, however, may be an effective way to survey these endparasitoids. The first evidence of hilltopping in species belonging to the subfamilies Myopinae and Dalmanniinae is presented and discussed. Field observations were conducted on Colle Vescovo, Italy and Mount Rigaud, Canada, and museum specimens were examined. Observations and records indicate that four species in the genera Dalmannia, Myopa, and Zodion are hilltoppers on Colle Vescovo, while three species in the genera Myopa and Physocephala are hilltoppers on three hilltops near Ottawa, Canada. Fifteen additional species of conopids have been collected on hilltops and could possibly utilize hilltops in some years as a part of their mating strategy. Detailed phenologies and observations of mating and perching behaviours are given for species in the genera Dalmannia, Myopa, Physocephala, and Zodion. The importance of hilltop habitat preservation is stressed. PMID- 20578950 TI - Effect of three bean species on the development and reproduction of a population of the parasitoid, Encarsia bimaculata, on the whitefly, Bemisia tabaci. AB - Developmental time, parasitism, emergence, longevity, fecundity and demographic parameters of population of Encarsia bimaculata Heraty and Polaszek (Hymenoptera: Aphelinidae), a parasitoid attacking Bemisia tabaci (biotype B) (Gennadius) (Homoptera: Aleyrodidae) infesting soybean, Glyine max L. (Merr), cowpea, Vigna unguiulata L. and garden bean, Phaseolus vulgaris L. (Fabeles: Fabaceae) were quantified and compared. Encarsia bimaculata was able to complete its life cycle independent of the B. tabaci instar parasitized. However, parasitoid development was significantly slower when first (19 d), second (15 d) instars or pharate adults (14 d) were parasitized compared to the third (13 d) or fourth (13 d) instars. Consequently, percent parasitism was higher when the third (51%) or fourth (46%) instars were parasitized compared to the first (22%), second (25%) instars or pharate adults (36%) of B. tabaci. Similarly, percent parasitoid emergence was significantly higher when third (83%) or fourth (76%) instars were parasitized compared to when the first (34%), second (64%) or pharate adults (54%) were parasitized. Host plant species significantly influenced egg to adult developmental time, percent parasitism and the day on which E. bimaculata nymphs hatching from eggs was first observed. More nymphs were parasitized on cowpea (40%) followed by garden bean (36%) and soybean (32%), while percent hatching was significantly higher on soybean (76%) followed by cowpea (68%) and garden bean (42%). Adult parasitoid females lived an average of 6.7 d on soybean, 7.6 d on cowpea and 7.2 d on garden bean and laid a lifetime average of 27 eggs on soybean, 31 eggs on cowpea and 30 eggs on garden bean. The daily mean fecundity of E. bimaculata was not significantly different on the three bean species. Life table parameters showed that the net reproductive rate (R(o)) was 14.50, generation time (T(c)) was 17.16, intrinsic rate of natural increase (r(m)) was 0.16, finite rate of growth (lambda) was 1.17 and doubling time (T(d)) was 4.44 for parasitoids on soybean. On cowpea, R(o) was 15.32, T(c) was 18.59, r(m) was 0.15, lambda was 1.16 and T(d) was 4.72, while, on garden bean, R(o) was 8.95, T(c) was 19.28, r(m) was 0.11, lambda was 1.12 and T(d) was 6.08. Given these life table parameters, higher population build up of the parasitoid will be expected on cowpea and soybean, respectively, compared to garden bean. Thus, for an effective augmentative release program involving E. bimaculata for the control of B. tabaci, it is important to take into consideration both the host stage of B. tabaci and the nature of the host plant on which it is developing. PMID- 20578951 TI - An arthropod enzyme, Dfurin1, and a vertebrate furin homolog display distinct cleavage site sequence preferences for a shared viral proprotein substrate. AB - Alphaviruses replicate in vertebrate and arthropod cells and utilize a cellular enzyme called furin to process the PE2 glycoprotein precursor during virus replication in both cell types. Furin cleaves PE2 at a site immediately following a highly conserved four residue cleavage signal. Prior studies demonstrated that the amino acid immediately adjacent to the cleavage site influenced PE2 cleavage differently in vertebrate and mosquito cells (HW Heidner et al. 1996 . Journal of Virology 70: 2069-2073.). This finding was tentatively attributed to potential differences in the substrate specificities of the vertebrate and arthropod furin enzymes or to differences in the carbohydrate processing phenotypes of arthropod and vertebrate cells. To further address this issue, we evaluated Sindbis virus replication and PE2 cleavage in the Chinese hamster, Cricetulus griseus Milne Edwards (Rodentia: Cricetidae) ovary cells (CHO-K1) and in a CHO-K1-derived furin negative cell line (RPE.40) engineered to stably express the Dfurin1 enzyme of Drosophila melanogaster Meigen (Diptera: Drosophilidae). Expression of Dfurin1 enhanced Sindbis virus titers in RPE.40 cells by a factor of 10(2)-10(3), and this increase correlated with efficient cleavage of PE2. The PE2-cleavage phenotypes of viruses containing different amino acid substitutions adjacent to the furin cleavage site were compared in mosquito (C6/36), CHO-K1, and Dfurin1 expressing RPE.40 cells. This analysis confirmed that the substrate specificities of Dfurin1 and the putative mosquito furin homolog present in C6/36 cells are similar and suggested that the alternative PE2 cleavage phenotypes observed in vertebrate and arthropod cells were due to differences in substrate specificity between the arthropod and vertebrate furin enzymes and not to differences in host cell glycoprotein processing pathways. PMID- 20578952 TI - Differential consumption of four aphid species by four lady beetle species. AB - The acceptability of four different aphid species Macrosiphum albifrons (Essig), Macrosiphum euphorbiae (Thomas), Macrosiphum pseudorosae Patch, and Myzus persicae (Sulzer) (Hemiptera: Aphididae), as prey for four lady beetle species, one native species Coccinella trifasciata L, and three non-native Coccinella septempunctata L, Harmonia axyridis Pallas, Propylea quatuordecimpunctata L (Coleoptera: Coccinellidae) were tested in the laboratory. The relative field abundance of adults of the same lady beetle species on host vegetation, Lupinus polyphyllus Lindley (Fabales: Fabaceae), Solanum tuberosum L (Solanales: Solanaceae), and Rosa multiflora Thunberg (Rosales: Rosaceae), both with and without aphids present was also observed. In the laboratory, H. axyridis generally consumed the most aphids, while P. quatuordecimpunctata consumed the fewest. The exception was P. quatuordecimpunctata, which consumed a greater number of M. albifrons nymphs, and C. trifasciata, which consumed a greater number of M. albifrons nymphs and adults, compared with the other two beetle species. Lady beetles consumed fewer M. albifrons compared with the other three aphid species, likely because of deterrent compounds sequestered by this species from its host plant. In the field, P. quatuordecimpunctata was the most abundant species found on L. polyphyllus and S. tuberosum. PMID- 20578953 TI - Host-feeding preference of the mosquito, Culex quinquefasciatus, in Yucatan State, Mexico. AB - Studies were conducted to determine the host-feeding preference of Culex quinquefasciatus Say (Diptera: Culicidae) in relation to the availability of human and domestic animals in the city of Merida, Yucatan State, Mexico. Mosquitoes were collected in the backyards of houses using resting wooden boxes. Collections were made five times per week from January to December 2005. DNA was extracted from engorged females and tested by PCR using universal avian- and mammalian-specific primers. DNA extracted from avian-derived blood was further analyzed by PCR using primers that differentiate among the birds of three avian orders: Passeriformes, Columbiformes and Galliformes. PCR products obtained from mammalian-derived blood were subjected to restriction enzyme digestion to differentiate between human-, dog-, cat-, pig-, and horse-derived blood meals. Overall, 82% of engorged mosquitoes had fed on birds, and 18% had fed on mammals. The most frequent vertebrate hosts were Galliformes (47.1%), Passeriformes (23.8%), Columbiformes (11.2%) birds, and dogs (8.8%). The overall human blood index was 6.7%. The overall forage ratio for humans was 0.1, indicating that humans were not a preferred host for Cx. quinquefasciatus in Merida. PMID- 20578954 TI - Acute and reproductive effects of Align, an insecticide containing azadirachtin, on the grape berry moth, Lobesia botrana. AB - Azadirachtin, derived from the neem tree, Azadirachta indica A. Juss (Sapindales: Meliaceae), seems promising for use in integrated pest management programs to control a variety of pest species. A commercial formulation of azadirachtin, Align, has been evaluated against different developmental stages of the European grape berry moth, Lobesia botrana Denis and Schiffermuller (Lepidoptera: Tortricidae). When administered orally, Align reduced the fecundity and fertility of adults treated with 1, 5, and 10 mg litre(-1). At the highest doses, fecundity and fertility were zero, but longevity was not affected. An LC(50) of 231.5 mg litre(-1) was obtained when Align was sprayed on eggs less than 1 day old. Hatching of all egg classes was significantly reduced, and this reduction was more pronounced for eggs less than 24 h old. LC(50) values of 2.1 mg litre(-1) for first instars and 18.7 mg litre(-1) for third instars were obtained when Align was present in the diet. Larvae reared on a diet containing different concentrations of Align did not molt into adults at the highest concentrations (0.3, 0.6, 1.2), and 50% molted at the lowest concentration (0.15). Phenotypic effects included inability to molt properly and deformities. The combination of acute toxicity and low, effective concentrations of Align observed in this study could lead to the inclusion of insecticides containing azadirachtin in integrated management programs against this pest. PMID- 20578955 TI - Determining the environmental factors underlying the spatial variability of insect appearance phenology for the honey bee, Apis mellifera, and the small white, Pieris rapae. AB - The spatial patterns of the variability of the appearance dates of the honey bee Apis mellifera L. (Hymenoptera: Apidea) and the small white Pieris rapae (L.) (Lepidoptera: Pieridae) were investigated in Spain. A database of more than 7,000 records of the dates of the first spring sightings of each species in more than 700 localities from 1952-2004 was used. Phenological data were related to spatial, topographical, climate, land use, and vegetation productivity explanatory variables by means of multiple regression models in order to search for the environmental mechanisms underlying the observable phenological variability. Temperature and altitudinal spatial gradients accounted for most of the spatial variability in the phenology of the studied species, while vegetation productivity and land use had low relevance. In both species, the first individuals were recorded at those sites with warmer springs and dry summers, at low altitudes, and not covered with dry farming (i.e., cereal crops). The identity and magnitude of the effect of the variables were almost identical for both species and closely mirrored spatial temperature gradients. The best explanatory models accounted for up to half of the variability of appearance dates. Residuals did not show a spatial autocorrelation, meaning that no other spatially structured variable at our working resolution could have improved the results. Differences in the spatial patterns of phenology with regard to other taxa, such as arrival dates of migratory birds, suggest that spatial constraints may play an essential role in the phenological matching between trophic levels. PMID- 20578956 TI - Histopathology caused by the entomopathogenic fungi, Beauveria bassiana and Metarhizium anisopliae, in the adult planthopper, Peregrinus maidis, a maize virus vector. AB - The planthopper Peregrinus maidis (Ashmead) (Hemiptera: Delphacidae) is an important vector of maize viruses in tropical and subtropical areas. Planthoppers are biologically controlled with several species of entomopathogenic fungi that have been isolated from these insect pests of rice in Asia. Beauveria bassiana (Balsamo-Crivelli) Vuillemin and Metarhizium anisopliae (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae) appear to be the most useful against planthoppers because of their ease of mass production, storage, virulence, and application. In the present study, adults of P. maidis infected with B. bassiana and M. anisopliae were observed under light and scanning electron microscopy to characterize morphologically the process of infection and the development of these fungi, prior to and after the death of the host. The hydrophobic conidia of both fungal species were able to attach to all body regions, with a preference for surfaces containing hairs. Few germinated conidia were observed on the insect's body surface at 24, 48, and 72 hr post-inoculation. On the cuticular surface of P. maidis treated with B. bassiana and M. anisopliae, bacillus-like bacteria were observed. These microorganisms could be interacting with fungal conidia, playing a role of antibiosis that will not allow the fungal pathogens to germinate and penetrate. In the colonization events observed in this study, the formation and multiplication of hyphal bodies by both fungal species inside the host's body was noted. The host's whole body was invaded by hyphae between five and six days post-inoculation, and body fat was the most affected tissue. PMID- 20578957 TI - Effect of insecticide regimens on biological control of the tarnished plant bug, Lygus lineolaris, by Peristenus spp. in New York State apple orchards. AB - To improve biological control of Lygus lineolaris (Palisot de Beauvois) (Hemiptera: Miridae), the European parasitoid Peristenus digoneutis Loan (Hymenoptera: Braconidae) was introduced into the US in the 1980's and has become established in forage alfalfa, strawberries and apples. The objective of this study was to determine how four different insecticide management regimes affected parasitism of L. lineolaris by Peristenus spp. During the summers of 2005 and 2006, L. lineolaris nymphs were collected from New York State apple orchards using industry standard, reduced risk, and organically approved insecticides only. A 'no insecticide' (abandoned orchard) treatment was also included in 2006. Rates of parasitism of L. lineolaris nymphs were determined using a DNA-based laboratory technique. Results indicated that insecticide treatment had a significant effect on rates of parasitism of L. lineolaris by Peristenus spp. Compared to the industry standard treatment, rates of parasitism were higher in reduced risk orchards and lower in organic orchards. These results suggest that it is difficult to predict a priori the consequences of insecticide programs and point to the need to take into consideration the specific pests and beneficial organisms involved as well as the crop and the specific insecticides being applied. PMID- 20578958 TI - Contribution of delayed intracellular pH recovery to ischemic postconditioning protection. AB - Ischemic postconditioning (PoCo) has been proven to be a feasible approach to attenuate reperfusion injury and enhance myocardial salvage in patients with acute myocardial infarction, but its mechanisms have not been completely elucidated yet. Recent studies demonstrate that PoCo may delay the recovery of intracellular pH during initial reperfusion, and that its ability to limit infarct size critically depends on this effect. Prolongation of postischemic intracellular acidosis inhibits hypercontracture, mitochondrial permeability transition, calpain-mediated proteolysis, and gap junction-mediated spread of injury during the first minutes of reflow. This role of prolonged acidosis does not exclude the participation of other pathways in PoCo-induced cardioprotection. On the contrary, it may allow these pathways to act by preventing immediate reperfusion-induced cell death. Moreover, the existence of interactions between intracellular acidosis and endogenous protection signaling cannot be excluded and needs to be investigated. The role of prolonged acidosis in PoCo cardioprotection has important implications in the design of optimal PoCo protocols and in the translation of cardioprotective strategies to patients with on-going myocardial infarction receiving coronary reperfusion. PMID- 20578959 TI - Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis. AB - Increased production of reactive oxygen species (ROS) as a result of decreased activities of mitochondrial electron transport chain (ETC) complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. Our previous studies established that paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. The aim of the present study was to determine the mechanism by which PON2 modulates ROS production. In this report, we demonstrate that PON2-def mice on the hyperlipidemic apolipoprotein E( /-) background (PON2-def/apolipoprotein E(-/-)) develop exacerbated atherosclerotic lesions with enhanced mitochondrial oxidative stress. We show that PON2 protein is localized to the inner mitochondrial membrane, where it is found associated with respiratory complex III. Employing surface-plasmon resonance, we demonstrate that PON2 binds with high affinity to coenzyme Q(10), an important component of the ETC. Enhanced mitochondrial oxidative stress in PON2-def mice was accompanied by significantly reduced ETC complex I + III activities, oxygen consumption, and adenosine triphosphate levels in PON2-def mice. In contrast, overexpression of PON2 effectively protected mitochondria from antimycin- or oligomycin-mediated mitochondrial dysfunction. Our results illustrate that the antiatherogenic effects of PON2 are, in part, mediated by the role of PON2 in mitochondrial function. PMID- 20578961 TI - Mitochondria in postconditioning. AB - Several signal transduction pathways are activated by cardioprotective stimuli, including ischemic or pharmacological postconditioning. These pathways converge on a common target, the mitochondria, and cardioprotection by postconditioning is associated with preserved mitochondrial function after ischemia/reperfusion. The present review discusses the role of mitochondria in cardioprotection, especially the involvement of ATP-dependent potassium channels, reactive oxygen species, and the mitochondrial permeability transition pore, and focuses on the effects of postconditioning on mitochondrial function (i.e., their oxygen consumption and calcium retention capacity). The contribution of mitochondria to loss of protection by postconditioning in diseased or aged myocardium is also addressed. PMID- 20578960 TI - Impacts of dietary selenium deficiency on metabolic phenotypes of diet-restricted GPX1-overexpressing mice. AB - We previously reported a spontaneous development of type 2 diabetes-like phenotypes in glutathione peroxidase-1 (GPX1)-overexpressing (OE) mice. Diet restriction of these mice rescued all their phenotypes, except for hyperinsulinemia and hypersecretion of insulin. This study was to determine whether dietary Se deficiency eliminated these two primary effects of GPX1 overproduction. Forty-seven male OE and wild-type (WT) mice were fed an Se adequate (0.4 mg Se/kg) or deficient (<0.02 mg Se/kg) diet at 2 to 3 g (full-fed = 5 g) per day from 4 to 12 weeks of age. Although dietary Se deficiency did not rescue the primary phenotypes of the diet-restricted OE mice, it exerted a strong effect (p < 0.05) on mRNA or protein levels (or both) of 14 molecules involved in islet insulin synthesis and secretion and hepatic lipogenesis. Dietary Se deficiency exhibited a hypoinsulinemic trend in OE mice and a strong hypolipidemic effect (p < 0.05) in the liver of WT mice. Hepatic lipogenesis was attenuated in OE compared with WT mice. In conclusion, diet restriction might be too overwhelming to allow a demonstration of a dietary Se-depletion effect on the OE phenotypes. Full-fed animals could offer a better chance to illustrate such effects and the underlying mechanisms. PMID- 20578963 TI - Postconditioning in acute myocardial infarction patients. AB - Reperfusion therapy is the indispensable treatment of acute myocardial infarction (AMI) and must be applied as soon as possible to attenuate the ischemic insult. Evidence indicates that reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore. Ischemic postconditioning is a new way to dramatically reduce the lethal reperfusion injury. Several clinical studies using angioplasty postconditioning now support its protective effects in patients with an AMI. An interesting alternative is pharmacological postconditioning, which could be applied to a much larger number of patients. The mitochondrial permeability transition pore inhibitor cyclosporine A has been shown to generate a comparable protection in AMI patients. Future large-scale trials are needed to determine whether postconditioning may improve clinical outcome in ST-segment elevation MI patients. PMID- 20578962 TI - Cardioprotection with postconditioning: loss of efficacy in murine models of type 2 and type-1 diabetes. AB - Postconditioning (PostC), or relief of myocardial ischemia in a stuttered manner, has been shown to reduce infarct size, due in part to upregulation of survival kinase signaling. Virtually all of these data have, however, been obtained in healthy adult cohorts; the question of whether PostC-induced cardioprotection is maintained in the setting of clinically relevant comorbidities has remained largely unexplored. Accordingly, our aim was to assess the consequences of a major risk factor-diabetes-on the infarct-sparing effect of stuttered reflow. Isolated buffer-perfused hearts were obtained from normoglycemic C57BL/6J mice, BKS.Cg-m+/+Lepr(db)/J (db/db) mice (model of type-2 diabetes), C57BL/6J mice injected with streptozotocin (model of type-1 diabetes), and streptozotocin injected mice in which normoglycemia was re-established by islet cell transplantation. All hearts underwent 30 min of ischemia and, within each cohort, hearts received either standard (control) reperfusion or three to six 10 s cycles of stuttered reflow. PostC reduced infarct size via upregulation of extracellular signal-regulated kinase 1/2 in normoglycemic mice. In contrast, diabetic hearts were refractory to PostC-induced cardioprotection-an effect that, in the type-1 model, was reversed by restoration of normoglycemia. We provide novel evidence for a profound-but potentially reversible-diabetes-induced defect in the cardioprotective efficacy of PostC. PMID- 20578964 TI - High resolution melting for the identification of mutations in the iron responsive element of the ferritin light chain gene. AB - BACKGROUND: Among the causes of hyperferritinemia, hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disease characterized by distinctive cataracts and high serum ferritin. It is caused by mutations in the iron responsive element (IRE) of the ferritin light chain gene (FTL). METHODS: To speed up and simplify mutational scanning in this genomic region, we developed a protocol based on high-resolution melting (HRM) analysis. RESULTS: Validation was carried out using 18 wild-type and 14 DNA samples carrying different mutations, each analyzed in replicates of 20. The method allowed for correct identification and genotyping of all mutant samples, and each variant generated a specific profile distinguishable from the wild type. A 5.5% proportion of false positive results were obtained. In addition, in two patients with HHCS, two new mutations were identified by HRM based on an altered melting profile. These mutations were subsequently characterized by direct sequencing (7C>G+40A>G and 49A>C). CONCLUSIONS: The high reliability of HRM in detecting known and new DNA variations indicate that this could be an effective and sensitive method for molecular scanning of mutations in the IRE of the FTL gene in patients presenting with either HHCS or unexplained hyperferritinemia. PMID- 20578965 TI - Errors in transfusion: causes and measures to avoid them. AB - Adverse events related to medical errors are common worldwide and largely unreported. However, they represent a serious problem within the health care community, resulting in avoidable loss of life and/or extremely high costs. Likewise, errors in transfusion medicine, which most frequently involve misidentification of the patient, not rarely may have life-threatening consequences. In this review, the errors related to blood transfusion are briefly summarized along with new technologies developed for improving blood safety. PMID- 20578966 TI - Coeliac disease--a diagnostic and therapeutic challenge. AB - During the past 20 years the diagnosis of coeliac disease has improved significantly. However, at the same time the true prevalence of the condition has doubled, involving more than 2% of the population in some countries. Due to mild or atypical symptoms, the diagnosis remains a challenge for the health care system. Highly sensitive and specific serum endomysial and transglutaminase-2 antibody tests are helpful in identifying patients for diagnostic endoscopy and small-bowel biopsy. The diagnosis of the disease is still based on the demonstration of gluten-induced small-bowel mucosal villous atrophy with crypt hyperplasia. However, coeliac disease may manifest itself before the development of the overt small-intestinal lesion. Positive endomysial and transglutaminase antibodies in patients with normal small-bowel mucosal villous architecture may indicate early stage coeliac disease. Currently, the only effective treatment for the condition is a life-long strict gluten-free diet. Long-term regular follow-up of patients is recommended in order to maintain good adherence to the diet. PMID- 20578967 TI - Serum soluble tumour necrosis factor receptor type I concentrations independently predict prognosis in patients with breast cancer. AB - BACKGROUND: The aim of this study was to exploit the potential clinical use of circulating cytokine assessment in patients with breast cancer. METHODS: The following circulating cytokines were measured in 210 histopathologically confirmed, untreated breast cancer patients: interleukin 6 (IL-6), tumour necrosis factor-alpha (TNFalpha), interleukin 8 (IL-8), soluble tumour necrosis factor receptor type I (sTNF RI), sTNF RII, interleukin 1 receptor antagonist (IL 1ra), interleukin 10 (IL-10), macrophage colony-stimulating factor, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The patients have been followed-up for 10 years. RESULTS: bFGF and VEGF showed the highest diagnostic sensitivity. Only IL-6 concentrations were related to the clinical stage. A high percentage of patients in clinical stage I showed increased serum sTNF RII, VEGF and bFGF concentrations, of which only sTNF RII was found to be increased in a smaller percentage of patients with more advanced disease compared with patients with early stage disease. Patients aged 50 years and more presented with significantly higher concentrations of sTNF RI, IL-10, IL 6 and VEGF compared with younger patients. In multivariate analysis, a significant value of pretreatment serum sTNF RI concentrations, next to stage and oestrogen receptors status, was its utility as an independent prognostic factor of the overall survival in patients with breast cancer. CONCLUSIONS: Serum sTNF RI may be considered an additional, independent and clinically useful factor of poor prognosis in patients with breast cancer. PMID- 20578968 TI - Quartz crystal microbalance-based biosensor for the detection of alpha thalassemia 1 (SEA deletion). AB - BACKGROUND: DNA piezoelectric biosensors have become a promising tool in molecular medicine since they do not require any label or staining. Here, a DNA piezoelectric biosensor based on a quartz crystal microbalance (QCM) was created to identify abnormal genes causing alpha-thalassemia 1 (SEA deletion). METHODS: The functionalized gold electrode of the quartz crystal was coated with avidin and the biotinylated DNA probe was attached. The target gene causing alpha thalassemia 1 was amplified and hybridized with the immobilized probe. DNA hybridization was indicated by changes in the quartz resonance frequencies. Diagnostic ability of the new alpha-thalassemia 1 biosensor was validated using both known and unknown blood samples. Specificity was tested using samples of beta-thalassemia and alpha-thalassemia 2. Stability of the sensor was also evaluated. RESULTS: The new biosensor could clearly identify alpha-thalassemia 1 (SEA deletion), both carrier and disease states, from the normal genotype. Identification accuracy was compatible to the standard gel electrophoresis. It was specific only to alpha-thalassemia 1 since no cross reaction was found with beta-thalassemia and alpha-thalassemia 2. The sensor could be kept at room temperature up to 6 months with consistent identification accuracy. CONCLUSIONS: The label free QCM based biosensor was successfully developed to diagnose an abnormal human globin gene causing alpha-thalassemia 1 (SEA deletion). Its accuracy, specificity and sensitivity were comparable to the standard method. Its stable diagnostic potency up to 6 months implied its field application in thalassemic control program. PMID- 20578969 TI - Development and evaluation of an automated hepatitis C virus NS5B sequence-based subtyping assay. AB - BACKGROUND: Hepatitis C virus (HCV) genotyping and accurate subtype determination is becoming increasingly important to better understand viral evolution, the development of resistance to STAT-C, and possibly even for the treatment and management of chronic HCV-infected patients. METHODS: A subtyping assay based on a 329-bp sequence of the NS5B region, together with an automated subtype interpretation tool was developed. Clinical samples of the six major genotypes were used to assess assay performance characteristics. RESULTS: The NS5B BLAST based subtyping assay showed clinical sensitivity for amplification of 89% (n=603 random samples). Assessment of analytical sensitivity of amplification for genotypes 1, 2, 3 and 4 revealed a suitable performance for high viral load samples and decreased only with low viral loads. The results were 100% and 99% accurate at the genotype and subtype level, respectively. A concordance of 97% on genotype level and 62% on subtype level was observed by comparison with subtype results from 5' non-coding-based assays with a panel of 276 isolates. CONCLUSIONS: The HCV NS5B subtyping assay has been validated for research use. Based on its performance, it is the method of choice in cases where subtype rather than genotype information is needed. PMID- 20578970 TI - DNA sequencing errors in molecular diagnostics of filamin myopathy. AB - BACKGROUND: Filamin myopathy is a neuromuscular disorder manifesting with predominantly limb-girdle muscle weakness and in many patients with diaphragm paralysis and cardiomyopathy, caused by mutations in the filamin C (FLNC) gene. Molecular diagnosis of filamin myopathy based on direct DNA sequencing of coding exons is compromised by the presence of a high homology pseudogene (pseFLNC) located approximately 53.6 kb downstream of the functional FLNC gene on chromosome 7q. METHODS: Molecular cloning, RT-PCR and real-time PCR methods were used to detect sequence differences between the FLNC and pseFLNC that are implicated in known or potential molecular diagnostic errors. Overall, 50 patients with a phenotype resembling filamin myopathy have been screened for mutations in FLNC. RESULTS: FLNC sequence inconsistencies caused by the interference from pseFLNC were identified and diagnostic errors involving, in particular, the detection of the most frequent disease-causing FLNC p.W2710X mutation resolved. Mismatches between the FLNC and pseFLNC sequences were tabulated for future use. CONCLUSIONS: We devise a strategy that allows one to discern mutations occurring in the functional FLNC from those harbored in pseFLNC, thus preventing possible complications in future research and patient genetic testing. PMID- 20578971 TI - Bioreactor landfill technology in municipal solid waste treatment: an overview. AB - In recent years, due to an advance in knowledge of landfill behaviour and decomposition processes of municipal solid waste, there has been a strong thrust to upgrade existing landfill technologies for optimizing these degradation processes and thereafter harness a maximum of the useful bioavailable matter in the form of higher landfill gas generation rates. Operating landfills as bioreactors for enhancing the stabilization of wastes is one such technology option that has been recently investigated and has already been in use in many countries. A few full-scale implementations of this novel technology are gaining momentum in landfill research and development activities. The publication of bioreactor landfill research has resulted in a wide pool of knowledge and useful engineering data. This review covers leachate recirculation and stabilization, nitrogen transformation and corresponding extensive laboratory- and pilot-scale research, the bioreactor landfill concept, the benefits to be derived from this bioreactor landfill technology, and the design and operational issues and research trends that form the basis of applied landfill research. PMID- 20578972 TI - Education effects on the International HIV Dementia Scale. AB - Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) within the Indian subcontinent continues to spread. Although the primary clade of HIV in India differs from that of most Western countries, recent evidence suggests that the Indian clade (Clade C) also impacts neurocognitive functioning. India also has extremely high illiteracy rates that may confound detection of neurocognitive impairment, since many assessments to detect such impairment are heavily influenced by formal schooling. Among those with HIV/AIDS who have had limited educational opportunities and who are in the early stage of infection, the confounding effects of education on tests for neurocognitive impairment may be particularly salient. We therefore tested influence of HIV serostatus and education on a commonly used tool to screen for cognitive impairment, the International HIV Dementia Scale (IHDS), among Indian men and women in the catchment area of the Post Graduate Institute of Medical Education and Research (PGIMER) located in Chandigarh, India. Adjusted analyses showed that from a sample of 295 HIV-positive and HIV-negative individuals, only education was significantly associated with performance on the IHDS. HIV-negative and HIV positive individuals, who were in the early stages of infection, performed similarly. Further development of this test to account for the effects of education on cut-off scores used to indicate possible dementia are needed, particularly for use in resource-limited settings such as India where low levels of education are widespread. PMID- 20578973 TI - Constituents of Limonia acidissima inhibit LPS-induced nitric oxide production in BV-2 microglia. AB - The ethyl acetate (EtOAc) soluble fraction of the 85% ethanol (EtOH) extract of the dried bark of Limonia acidissima potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS) activated BV-2 cells, a microglial cell line. Bioassay-guided column chromatography separation afforded a new stereoisomer of neolignan, (7'E)-(7R,8S)-4-hydroxy-3,5'-dimethoxy-4',7-epoxy-8,3' neolig-7'-en-9,9'-diyil diacetate (1), together with two known lignans, (+) yangambin (2) and (+)-syringaresinol (3), three known triterpenoids, hederatriol (4), basic acid methyl ester (5), and 3beta-hydroxyolean-12-en-11-one (6), and four known fatty acid derivatives, cascarillic acid (7), (+)-alpha-dimorphecolic acid (8), 8(R)-hydroxylinoleic acid (9), and (6Z,9Z,12Z)-pentadecatrienoic acid (10). The structure of the new compound 1 was elucidated by detailed analysis of spectroscopic data and circular dichroism (CD) spectroscopy. Compounds 1, 3-6, and 8-10 isolated from L. acidissima significantly reduced NO production in LPS stimulated BV-2 microglia cells. PMID- 20578975 TI - The use of sound during exercise to assist development for children with and without movement difficulties. AB - PURPOSE: To identify and review the literature on the role of sound in facilitating movement and development. The emphasis was to consider the role of sound during exercise and rehabilitation and to encourage researchers to further explore the role of sound in movement development and rehabilitation. METHODS: A review of key and relevant literature was conducted. Data related to the proof-of concept of a ball emitting broadband sound to enhance motor development in children with and without movement disorders is presented. RESULTS: Analyses of the data indicated an interaction between group and block of training (p 90%). The present results suggest that investigation of the effect of multiple dosing at later time points to further improve survival is warranted. PMID- 20579074 TI - Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions. AB - Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a well recognized entity. However, the molecular underpinnings of this devastating disease are poorly understood. Here, we present genetic and neuropathological characterizations in two young women with fatal rapidly progressive ALS with basophilic inclusions. In one case, a germline mutation (P525L) was detected in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene, whereas no mutation was identified in the other case. Postmortem examination in both cases revealed severe loss of spinal motor neurons with remaining neurons showing basophilic inclusions that contain abnormal aggregates of FUS proteins and disorganized intracellular organelles, including mitochondria and endoplasmic reticulum. In both patients, the FUS-positive inclusions were also detected in neurons in layers IV-V of cerebral cortex and several brainstem nuclei. In contrast, spinal motor neurons in patients with late-onset sporadic ALS showed no evidence of abnormal accumulation of FUS protein. These results underscore the importance of FUS mutations and pathology in rapidly progressive juvenile ALS. Furthermore, our study represents the first detailed characterizations of neuropathological findings in rapidly progressive juvenile ALS patients with a mutation in the FUS/TLS gene. PMID- 20579076 TI - Targeting solid tumors with non-pathogenic obligate anaerobic bacteria. AB - Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. PMID- 20579077 TI - Novel VKORC1 mutations associated with warfarin sensitivity. AB - Warfarin is widely used anticoagulant drug for the prophylaxis and treatment of venous and arterial thromboembolic disorders and exerts its anticoagulant effect by inhibiting the vitamin K epoxide reductase. To determine the impact of genetic variants of the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) on the anticoagulant response to warfarin, polymorphisms in exon 1, exon 3, and 3' untranslated region (3' UTR) were assessed. RESULTS: Sixty patients (34 males and 26 females) with stable INR (2-3) were selected from cardiology and anticoagulant clinic. Three VKORC1 frameshift mutations were detected. The first frameshift mutation was nucleotide deletion (91delCC) in exon 3 (1 patient). The second variation was nucleotide addition (51addCT) in exon 3 (2 patients). All the 3 patients reported bleeding during warfarin use, while no other bleeding was reported during the study period. Warfarin maintenance dose was significantly different between 3 patients with mutations and patients without mutations. The use of a fixed-dose warfarin for all patients and in range INR may not be sufficient for warfarin monitoring. Many factors including unknown ones may also play an important role in highly variable response among patients. Our data for the first time, suggested a new possible call for screening to reduce the risk of bleeding and guide for dosing. PMID- 20579078 TI - Exploring retinal and functional markers of diabetic neuropathy. AB - Diabetic peripheral neuropathy (DPN) is one of the most debilitating complications of diabetes. DPN is a major cause of foot ulceration and lower limb amputation. Early diagnosis and management are key factors in reducing morbidity and mortality. Current techniques for clinical assessment of DPN are relatively insensitive for detecting early disease or involve invasive procedures such as skin biopsies. There is a need for less painful, non-invasive, safe evaluation methods. Eye-care professionals already play an important role in the management of diabetic retinopathy but recent studies have indicated that the eye may also be an important site for the diagnosis and monitoring of neuropathy. Corneal nerve morphology is a promising marker of diabetic neuropathy occurring elsewhere in the body. Emerging evidence tentatively suggests that retinal anatomical markers and a range of functional visual indicators could similarly provide useful information regarding neural damage in diabetes, although this line of research is less well established. This review outlines the growing body of evidence supporting a potential diagnostic role for retinal structure and visual functional markers in the diagnosis and monitoring of peripheral neuropathy in diabetes. PMID- 20579079 TI - Relationship between corneal topographical changes and subjective myopic reduction in overnight orthokeratology: a retrospective study. AB - BACKGROUND: To investigate the relationship between the change in the manifest refractive error (DeltaM), the change in apical corneal power (DeltaACP) and initial corneal asphericity (Q) in overnight orthokeratology (ortho-K). METHODS: One hundred and twenty-eight clinical records of children undergoing ortho-K from a university optometry clinic were reviewed. The refractive and topographical data at baseline and at two-week visit of 58 patients who fulfilled the inclusion criteria were retrieved and analysed. RESULTS: Significant differences (p < 0.001) between the change in manifest refractive error and changes in the apical corneal power or the maximum change in corneal power (DeltaMCP) within the treatment zone were found. Linear regression analysis was used to describe the change in manifest refractive error and the change in apical corneal power, and the change in manifest refractive error and the maximum change in corneal power, with the equations: DeltaM = 0.91DeltaACP + 0.57 (r = 0.78, p < 0.001) and DeltaM = 0.93DeltaMCP + 0.01 (r = 0.79, p < 0.001) respectively. On average, the change in apical corneal power underestimated the change in manifest refractive error by 0.34 +/- 0.57 D; whereas on average, the maximum change in corneal power overestimated the change in manifest refractive error by 0.23 +/- 0.57 D (paired t-tests, p < 0.001). A low but significant correlation between initial corneal asphericity and the change in manifest refractive error (Spearman r = -0.33, p = 0.01) was observed. CONCLUSIONS: The change in apical corneal power underestimates the change in manifest refractive error in ortho-K, whereas the maximum change in corneal power overestimates this parameter. Compared with retinoscopy and autorefraction, the change in apical corneal power is still useful for estimation of the change in manifest refractive error. Although the maximum change in corneal power appears to give a closer estimation of the change in manifest refractive error than the change in apical corneal power, there is no advantage in the use of maximum corneal power (manually located) instead of apical corneal power (a default given by the topographer) to estimate the change in manifest refractive error, as there is no significant difference in the estimations by either parameter. Initial corneal asphericity measured by the Medmont E300 corneal topographer has limited usage in predicting the change in manifest refractive error in overnight ortho-K. PMID- 20579081 TI - Cortical blindness due to bilateral embolism: a rare complication of cardiac catheterisation. PMID- 20579080 TI - Trends in Australian contact lens prescribing during the first decade of the 21st Century (2000-2009). AB - PURPOSE: The aim was to document contact lens prescribing trends in Australia between 2000 and 2009. METHODS: A survey of contact lens prescribing trends was conducted each year between 2000 and 2009. Australian optometrists were asked to provide information relating to 10 consecutive contact lens fittings between January and March each year. RESULTS: Over the 10-year survey period, 1,462 practitioners returned survey forms representing a total of 13,721 contact lens fittings. The mean age (+/- SD) of lens wearers was 33.2 +/- 13.6 years and 65 per cent were female. Between 2006 and 2009, rigid lens new fittings decreased from 18 to one per cent. Low water content lenses reduced from 11.5 to 3.2 per cent of soft lens fittings between 2000 and 2008. Between 2005 and 2009, toric lenses and multifocal lenses represented 26 and eight per cent, respectively, of all soft lenses fitted. Daily disposable, one- to two-week replacement and monthly replacement lenses accounted for 11.6, 30.0 and 46.5 per cent of all soft lens fittings over the survey period, respectively. The proportion of new soft fittings and refittings prescribed as extended wear has generally declined throughout the past decade. Multi-purpose lens care solutions dominate the market. Rigid lenses and monthly replacement soft lenses are predominantly worn on a full-time basis, whereas daily disposable soft lenses are mainly worn part time. CONCLUSIONS: This survey indicates that technological advances, such as the development of new lens materials, manufacturing methods and lens designs, and the availability of various lens replacement options, have had a significant impact on the contact lens market during the first decade of the 21st Century. PMID- 20579083 TI - Abstracts of the 16th International Symposium on Infections in the Immunocompromised Host. June 27-28, 2010. Budapest, Hungary. PMID- 20579082 TI - Orbital metastasis secondary to breast cancer mimicking thyroid-associated ophthalmopathy. PMID- 20579084 TI - What are the indications for a stoma in Fournier's gangrene? AB - AIM: This study examined the indications for a stoma in patients with Fournier's gangrene and its impact on outcome. METHOD: Patients with Fournier's gangrene were retrospectively reviewed for indications for a stoma. Patients with and without a stoma were compared, based on demographics, disease severity, surgical therapy, length of hospital stay, clinical outcome and cost. RESULTS: Forty-four patients (median age 57 years, range 28-77 years) were evaluated. Eighteen had a temporary stoma and 26 did not. A stoma was 5 times more likely in males. Patients with Fournier's gangrene originating from an anorectal disorder received a stoma more often than patients with disease originating from an urogenital disorder. Clinical outcomes were similar for patients with or without a stoma. Stoma closure was associated with an extra cost of about $6650 per patient. CONCLUSION: Stoma creation in the management of Fournier's gangrene was needed for selected patients. Having a stoma did not appear to affect outcomes and resulted in a significant increase in cost of care. PMID- 20579085 TI - Sacral nerve stimulation for the treatment of faecal incontinence after ileal pouch anal anastomosis. PMID- 20579087 TI - Adapting human societies to conservation. PMID- 20579088 TI - A REDD light for wildlife-friendly farming. PMID- 20579089 TI - Prevention of secondary extinctions through taxon substitution. PMID- 20579090 TI - Extirpations from parks: scaling conservation planning to fit the problem. PMID- 20579095 TI - Abstracts of the European Academy of Childhood Disability 22nd Annual Meeting. May 26-29, 2010. Brussels, Belgium. PMID- 20579096 TI - Opportunistic respiratory pathogens in the oral cavity of the elderly. AB - The oral cavity of the hospitalized or bedridden elderly is often a reservoir for opportunistic pathogens associated with respiratory diseases. Commensal flora and the host interact in a balanced fashion and oral infections are considered to appear following an imbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. The definition of the process involved in colonization by opportunistic respiratory pathogens needs to elucidate the factors responsible for the transition of the microbiota from commensal to pathogenic flora. The regulatory factors influencing the oral ecosystem can be divided into three major categories: the host defense system, commensal bacteria, and external pathogens. In this article, we review the profile of these categories including the intricate cellular interaction between immune factors and commensal bacteria and the disturbance in homeostasis in the oral cavity of hospitalized or bedridden elderly, which facilitates oral colonization by opportunistic respiratory pathogens. PMID- 20579097 TI - Effects of clinical isolates of Pseudomonas aeruginosa on Staphylococcus epidermidis biofilm formation. AB - Pseudomonas aeruginosa is often found in chronic infections, including cystic fibrosis lung infections and those related to chronic wounds and venous ulcers. At the latter sites, P. aeruginosa can be isolated together with Staphylococcus epidermidis, and we have therefore explored the effect of clinical isolates and laboratory strains of P. aeruginosa strains on colonization by S. epidermidis in dual-species biofilms. Biofilm formation was assayed using 16S rRNA FISH and confocal laser scanning microscopy. Among the six P. aeruginosa strains tested, one particular strain, denoted 14:2, exerted a significant inhibitory effect, and even after 6 h, S. epidermidis levels in dual-species biofilms were reduced by >85% compared with those without P. aeruginosa. Interestingly, strain 14:2 was found to be negative for classical virulence determinants including pyocyanin, elastase and alkaline protease. Therefore, we suggest that less virulent phenotypes of P. aeruginosa, which may develop over time in chronic infections, could counteract colonization by S. epidermidis, ensuring persistence and dominance by P. aeruginosa in the host micro-habitat. Further studies are required to explain the inhibitory effect on S. epidermidis, although extracellular polysaccharides produced by P. aeruginosa might play a role in this phenomenon. PMID- 20579098 TI - The immune system vs. Pseudomonas aeruginosa biofilms. AB - Ilya Metchnikoff and Paul Ehrlich were awarded the Nobel price in 1908. Since then, numerous studies have unraveled a multitude of mechanistically different immune responses to intruding microorganisms. However, in the vast majority of these studies, the underlying infectious agents have appeared in the planktonic state. Accordingly, much less is known about the immune responses to the presence of biofilm-based infections (which is probably also due to the relatively short period of time in which the immune response to biofilms has been studied). Nevertheless, more recent in vivo and in vitro studies have revealed both innate as well as adaptive immune responses to biofilms. On the other hand, measures launched by biofilm bacteria to achieve protection against the various immune responses have also been demonstrated. Whether particular immune responses to biofilm infections exist remains to be firmly established. However, because biofilm infections are often persistent (or chronic), an odd situation appears with the simultaneous activation of both arms of the host immune response, neither of which can eliminate the biofilm pathogen, but instead, in synergy, causes collateral tissue damage. Although the present review on the immune system vs. biofilm bacteria is focused on Pseudomonas aeruginosa (mainly because this is the most thoroughly studied), many of the same mechanisms are also seen with biofilm infections generated by other microorganisms. PMID- 20579099 TI - Ability of Pseudoalteromonas tunicata to colonize natural biofilms and its effect on microbial community structure. AB - We investigated the effectiveness of surface colonization by the epiphytic marine bacterium Pseudoalteromonas tunicata firstly on a complex biofilm community on glass slides, and secondly, on the epiphytic community of Ulva australis. The effectiveness of P. tunicata was compared with the performance of Phaeobacter sp. 2.10, also a marine epiphytic isolate in the U. australis colonization experiments. Pseudoalteromonas tunicata cells were able to colonize the glass slide community at densities found naturally in the water column (9.7 x 10(4) cells mL(-1)). However, P. tunicata was a poor invader of the epiphytic community on U. australis at densities of 10(6) cells mL(-1). At densities of 10(8) cells mL(-1), P. tunicata again exerted little impact on the epiphytic community. Phaeobacter sp. 2.10 was also a poor invader at lower densities, but was able to invade and become dominant at densities of 10(8) cells mL(-1). Differences in the ability of P. tunicata and Phaeobacter sp. 2.10 to invade natural communities may be due to differences in the antibacterial compounds produced by the two species. These experiments suggest that epiphytic communities may have protective effects compared with inanimate surfaces. PMID- 20579100 TI - Metronidazole effects on microbiota and mucus layer thickness in the rat gut. AB - Both mucus and mucosa-associated bacteria form a specific environment in the gut; their disruption may play a crucial role in the development of intestinal bowel disease (IBD). Metronidazole, an antibiotic used in the treatment of IBD, alters gut microbiota and reduces basal oxidative stress to proteins in colonic tissue of healthy rats. The aim of this study was to evaluate the impact of the altered microbiota due to the metronidazole on the thickness of the mucus layer. This study was performed in healthy untreated rats (control group) or rats treated by metronidazole (metronidazole-treated rats, 1 mg mL(-1) in drinking water for 7 days). Both PCR-temporal temperature gradient gel electrophoresis and quantitative PCR (qPCR) revealed an altered microbiota with an increase in bifidobacteria and enterobacteria in metronidazole-treated rats compared with control rats. Moreover, a dominant bifidobacterial species, Bifidobacterium pseudolongum, was detected. Using qPCR and FISH, we showed that bifidobacteria were also increased in the microbiota-associated mucosa. At the same time, the mucus layer thickness was increased approximately twofold. These results could explain the benefits of metronidazole treatment and warrant further investigations to define the role of bifidobacteria in the colonic mucosa. PMID- 20579101 TI - In vitro effects of synbiotic fermentation on the canine faecal microbiota. AB - Stirred, pH-controlled anaerobic batch cultures were used to investigate the in vitro effects of galacto-oligosaccharides (GOS) alone or combined with the probiotic Bifidobacterium bifidum 02 450B on the canine faecal microbiota of three different donors. GOS supported the growth of B. bifidum 02 450B throughout the fermentation. Quantitative analysis of bacterial populations by FISH revealed significant increases in Bifidobacterium spp. counts (Bif164) and a concomitant decrease in Clostridium histolyticum counts (Chis150) in the synbiotic-containing vessels compared with the controls and GOS vessels. Vessels containing probiotic alone displayed a transient increase in Bifidobacterium spp. and a transient decrease in Bacteroides spp. Denaturing gradient gel electrophoresis analysis showed that GOS elicited similar alterations in the microbial profiles of the three in vitro runs. However, the synbiotic did not alter the microbial diversity of the three runs to the same extent as GOS alone. Nested PCR using universal primers, followed by bifidobacterial-specific primers illustrated low bifidobacterial diversity in dogs, which did not change drastically during the in vitro fermentation. This study illustrates that the canine faecal microbiota can be modulated in vitro by GOS supplementation and that GOS can sustain the growth of B. bifidum 02 450B in a synbiotic combination. PMID- 20579103 TI - Phylogenetic diversity of T4-like bacteriophages in Lake Baikal, East Siberia. AB - Among the tailed phages, the myoviruses, those with contractile tails, are widespread and diverse. An important component of the Myoviridae family is the genus 'T4-like viruses'. The present study was aimed at elucidating the molecular diversity of T4-type bacteriophages in Lake Baikal by partial sequencing of g23 genes of T4-type bacteriophages. Our study revealed that the g23 gene sequences investigated were highly diverse and different from those of T4-like bacteriophages and from g23 clones obtained from different environments. Phylogenetic analysis showed that all g23 fragments from Lake Baikal, except for the one sequence, were more closely related to marine T4 cyanophages and to previously described subgroups of uncultured T4 phages from marine and rice field environments. PMID- 20579104 TI - Regulatory circuits in Helicobacter pylori : network motifs and regulators involved in metal-dependent responses. AB - The ability of Helicobacter pylori, one of the most successful human bacterial pathogens, to colonize the acidic gastric niche persistently, depends on the proper homeostasis of intracellular metal ions, needed as cofactors of essential metallo-proteins involved in acid acclimation, respiration and detoxification. This fundamental task is controlled at the transcriptional level mainly by the regulators Fur and NikR, involved in iron homeostasis and nickel response, respectively. Herein, we review the molecular mechanisms that underlie the activity of these key pleiotropic regulators. In addition, we will focus on their involvement in the transcriptional regulatory network of the bacterium, pinpointing a surprising complexity of network motifs that interconnects them and their gene targets. These motifs appear to confer versatile dynamics of metal dependent responses by extensive horizontal connections between the regulators and feedback control of metal-cofactor availability. PMID- 20579105 TI - Simple is good: yeast models of neurodegeneration. AB - The budding yeast, Saccharomyces cerevisiae, is the best-studied eukaryotic cell, at both genetic and physiological levels. As a eukaryote, yeast shares highly conserved molecular and cellular mechanisms with human cells. Thus, this simple fungus is an invaluable model to study the fundamental molecular mechanisms involved in several human diseases. In the particular case of neurodegenerative disorders, yeast models have been able to recapitulate several important features of complex and devastating disorders, such as Huntington's and Parkinson's diseases. Once validated, these models have also been used to accelerate the identification of both novel therapeutic targets and compounds with therapeutic potential. Here, we review the recent contributions of this simple, but powerful model organism toward our understanding of neurodegeneration. PMID- 20579106 TI - An oleate-stimulated, phosphatidylinositol 4,5-bisphosphate-independent phospholipase D in Schizosaccharomyces pombe. AB - Phospholipase D1 (PLD1) is an important enzyme involved in lipid-mediated signal transduction and membrane dynamics in eukaryotes. PLD1 preferentially hydrolyzes phosphatidylcholine to phosphatidic acid. This potent second messenger is involved in cytoskeletal reorganization, secretion, and membrane trafficking in eukaryotic cells. In Saccharomyces cerevisiae, PLD1 is involved in polarized growth and morphogenesis during pheromone response and sporulation. The presence of a PLD activity in Schizosaccharomyces pombe is demonstrated. PLD activity was able to hydrolyze a fluorescently labeled analog of phosphatidylcholine and was capable of performing the transphosphatidylation reaction characteristic of PLDs. Schizosaccharomyces pombe PLD activity was unaffected by phosphatidylinositol 4,5 bisphosphate (PIP(2)), but was slightly stimulated by oleate. PLD activity was shown to increase when the S. pombe cells underwent mating and sporulation. Here, we also report the molecular cloning of the first phospholipase D isoform from an S. pombe genomic DNA library (EMBL accession no. FN547388). Comparisons of three divergent yeasts, S. pombe, S. cerevisiae, and Candida albicans, with respect to the PLD enzymes revealed differences in regulation by oleate and PIP(2). Even with high homology in the protein sequences between the PLD1 enzymes of S. cerevisiae, C. albicans, and S. pombe, there was variation with the effects of the regulators. PMID- 20579108 TI - Factors affecting the distribution and prevalence of oral mucosal lesions in complete denture wearers. AB - OBJECTIVE: To determine the frequency of the oral lesions related to gender, age, the length of time of denture usage, education level and economic status. METHODS: The 153 patients with old complete dentures (CD) were asked to participate in the investigation. The subjects (76 male and 77 female) were 37-85 years of age with a mean age of 61.8 +/- 9.8 years. Education, economic status and age factors were estimated in subgroups. The data obtained were evaluated by one-way anova, Mann-Whitney U-test, Kruskal-Wallis test, Student's t-test and chi squared test. The level of statistical significance was set at p<0.05. RESULTS: The patients who had denture stomatitis and traumatic ulcers were statistically significantly older than the ones who did not have these lesions (p<0.05). Based on the length of denture usage, patients who had a flabby ridge, fibrous inflammatory hyperplasia, traumatic ulcers (p<0.01) and denture stomatitis (p<0.05) were using their dentures statistically significantly longer than the ones who had healthy tissues. CONCLUSIONS: The CD wearers should be advised to visit their dentist regularly to prevent oral mucosal lesions due to the changing supporting tissues during the length of denture usage and to improve their quality of life. PMID- 20579107 TI - Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication. AB - Comparative analyses used to reconstruct the evolution of traits associated with the human language faculty, including its socio-cognitive underpinnings, highlight the importance of evolutionary constraints limiting vocal learning in non-human primates. After a brief overview of this field of research and the neural basis of primate vocalizations, we review studies that have addressed the genetic basis of usage and structure of ultrasonic communication in mice, with a focus on the gene FOXP2 involved in specific language impairments and neuroligin genes (NL-3 and NL-4) involved in autism spectrum disorders. Knockout of FoxP2 leads to reduced vocal behavior and eventually premature death. Introducing the human variant of FoxP2 protein into mice, in contrast, results in shifts in frequency and modulation of pup ultrasonic vocalizations. Knockout of NL-3 and NL 4 in mice diminishes social behavior and vocalizations. Although such studies may provide insights into the molecular and neural basis of social and communicative behavior, the structure of mouse vocalizations is largely innate, limiting the suitability of the mouse model to study human speech, a learned mode of production. Although knockout or replacement of single genes has perceptible effects on behavior, these genes are part of larger networks whose functions remain poorly understood. In humans, for instance, deficiencies in NL-4 can lead to a broad spectrum of disorders, suggesting that further factors (experiential and/or genetic) contribute to the variation in clinical symptoms. The precise nature as well as the interaction of these factors is yet to be determined. PMID- 20579110 TI - Confronting the psychological burden of haemophilia. AB - Providing comprehensive care, counselling and support to haemophilic patients, and their parents have always been quite complex for haemophilia treatment centres. Nowadays, starting with recent developments in genetic counselling, prenatal diagnosis and carrier testing, the psychological burden on patients and parents might possibly have increased, compared with even the recent past. The emotional strains and worries associated with a possibly affected newborn and his care through childhood and adolescence may also have a grievous impact on couple dynamics and marital relationship. The impact may be even higher in families in which haemophilia is newly diagnosed. The main psychological problems faced by parents and then by affected individuals are herein chronologically reviewed, starting from genetic counselling before conception through childhood, adolescence and adulthood. Aware of the psychosocial burden on patients and their families associated with haemophilia, from prenatal diagnosis and carrier testing until later stages of life of the affected individual, a board of Italian haemophilia specialists and psychologists is designing and organizing an innovative network of psychological support services in some Italian haemophilia centres and promoting specific educational programmes in this setting. PMID- 20579111 TI - Low dose secondary prophylaxis reduces joint bleeding in severe and moderate haemophilic children: a pilot study in China. AB - The most common bleeding in haemophilic patients is in joints, and joint disability is the most common complications in these patients receiving inadequate treatment. Limited by economy and inadequate treatment, developing countries face huge challenge to reduce disability and improve quality of life (QoL) of haemophilic children. The aim of this study was to investigate the effect of low dose secondary prophylaxis in China. Children with moderate and severe haemophilia from the Beijing Children Hospital, Beijing, China, and with established joint disease, were followed for a 12-week observation period followed by a 12-week low dose secondary prophylaxis-study period (for haemophilia A, factor VIII concentrate 10 IU kg(-1) twice weekly; for haemophilia B, factor IX concentrate 20 IU kg(-1) weekly). The reduction of joint bleeding, improvement of joint function and QoL during prophylaxis were analysed. In total 34 children (median age 7.8 years) were analyzable. The number of joint bleeds decreased from a total of 337 (individual range 3-24, mean 9.9) during the observation period to 57 (range 0-6, mean 1.7) during the study period with an overall of reduction 83%. Joint function improved in 66.7% of disease joints, with 23.2% of which were considered good to moderate. School attendance improved in all subjects, sports participation and daily activity improved moderately. Low dose secondary prophylaxis significantly reduces frequency of joint bleeding; with moderate improvement in joint function, school attendance, sport participation and daily activities. Low dose secondary prophylaxis is therefore, cost-effective as applied to developing countries such as China, although there are still unresolved issues. PMID- 20579112 TI - Evaluation of factor VIII pharmacokinetics and anti-factor VIII antibodies in four boys with haemophilia A and a poor clinical response to factor VIII. PMID- 20579113 TI - Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method] demonstrates efficacy, safety and low risk for immunogenicity in routine clinical practice. AB - Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method, (rAHF-PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on-demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII<=2%, three (0.75%) developed low-titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII<=2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01-1.59%). A PTP with moderate haemophilia developed a low titre inhibitor. High-titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF-PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies. PMID- 20579115 TI - A marvellous and authentic account: the first written report of haemophilia in America. AB - The first written record of haemophilia in America is reputed to be the 1791 newspaper obituary of Isaac Zoll. The earlier, original publication of this obituary is identified. PMID- 20579114 TI - Awaiting evidence-based recommendations on prophylaxis in adult patients. PMID- 20579116 TI - Exceptionally good? Positive experiences of NHS care and treatment surprises lymphoma patients: a qualitative interview study. AB - OBJECTIVE: Initial analysis of an interview study with patients about their experiences of lymphoma identified a strong emergent theme suggesting people were surprised to receive good care in the UK National Health Service. This qualitative analysis helps illuminate the disparity between public perceptions of NHS care and individual experiences. PARTICIPANTS AND SETTING: Forty-one women and men with lymphoma were interviewed at home by an academic social scientist; nine who had had all their treatment before 1997 were excluded from this analysis. DESIGN: Initial qualitative thematic analysis used constant comparison and axial coding. Using narrative analytic methods, we explored how the accounts of positive experiences were structured and framed as well as what was said. RESULTS: Every person we interviewed described positive experiences of the NHS. These included the skills and humanity of the specialist staff involved in their care, the team work, the organization of care and communication and information. However, these positive experiences were often framed as personal good fortune rather than an indication that a high standard might be expected of NHS cancer care. Participants' accounts also suggest a discrepancy through the use of framing devices that imply that less professional, kind and caring treatment might be expected. CONCLUSION: People may be able to maintain the apparently contradictory opinions that the NHS is not very good, even if their own experience of care is excellent, if they construct their own experience as 'lucky'. Health professionals could help by reassuring patients with a more positive, realistic expectation of specialist care. PMID- 20579117 TI - 'Never heard of it'- understanding the public's lack of awareness of a new electronic patient record. AB - BACKGROUND: The introduction of electronic patient records that are accessible by multiple providers raises security issues and requires informed consent - or at the very least, an opportunity to opt out. Introduction of the Summary Care Record (SCR) (a centrally stored electronic summary of a patient's medical record) in pilot sites in the UK was associated with low awareness, despite an intensive public information programme that included letters, posters, leaflets, and road shows. AIM: To understand why the public information programme had limited impact and to learn lessons for future programmes. METHODS: Linguistic and communications analysis of components of the programme, contextualized within a wider mixed-method case study of the introduction of the SCR in pilot sites. Theoretical insights from linguistics and communication studies were applied. RESULTS: The context of the SCR pilots and the linked information programme created inherent challenges which were partially but not fully overcome by the efforts of campaigners. Much effort was put into designing the content of a mail merge letter, but less attention was given to its novelty, linguistic style, and rhetorical appeal. Many recipients viewed this letter as junk mail or propaganda and discarded it unread. Other components of the information programme were characterized by low visibility, partly because only restricted areas were participating in the pilot. Relatively little use was made of interpersonal communication channels. CONCLUSION: Despite ethical and legal imperatives, informed consent for the introduction of shared electronic records may be difficult to achieve through public information campaigns. Success may be more likely if established principles of effective mass and interpersonal communication are applied. PMID- 20579118 TI - Are elected health boards an effective mechanism for public participation in health service governance? AB - BACKGROUND: There is growing interest in the idea of elected members on health service governing boards as a means to induce public participation in planning and decision making, yet studies of elected boards are limited. Whether elected boards are an effective mechanism for public participation remains unclear. SETTING AND PARTICIPANTS: This article discusses the experiences of New Zealand where, since 2001, there have been three sets of elections for District Health Boards. Information on candidates and election results is presented along with data gathered via post-election voter surveys. The article also considers the broader regulatory context within which the elected boards must operate. DISCUSSION AND CONCLUSIONS: The New Zealand experience illustrates that elected health boards may not be an effective mechanism for public participation. Voter turnout has declined since the inaugural elections of 2001, and non-voters form the majority. Reasons for not voting include failure to receive voting papers, a lack of interest, or no knowledge of elections. The elections have also failed to produce minority representation, while the capacity for elected members to represent their communities is subject to constraints. On the upside, elections have enabled public involvement in various dimensions of participation, including oversight and processes of governance. New Zealand's mixed performance suggests that elected boards may need to be complemented with other participatory channels, if increased public participation is the goal. PMID- 20579119 TI - The PRIME project: developing a patient evidence-base. AB - BACKGROUND: The concept of evidence has become firmly rooted in health care, with most importance placed on the outcome of research in clinical and economic spheres. Much less emphasis is placed on the patient's contribution to evidence which remains relatively vague, of low status and often difficult to integrate with other forms of knowledge. AIM: This article proposes a concept of patient based evidence, to complement clinical and economic forms of evidence, and demonstrates one way in which it has been operationalized. The PRIME project developed a patient evidence-base to capture the lived experience of individuals with myalgic encephalitis (ME) or chronic fatigue syndrome (CFS). DESIGN: Interviews were performed with 40 individuals with ME/CFS who varied in a range of demographic characteristics, including age, gender, and how severely affected individuals were. RESULTS: PRIME has developed a patient evidence-base which has an extensive array of experiences data to provide researchers, clinicians and others with an in-depth insight into the lived experience of ME/CFS that can be used and analysed. Data are grouped into a wide range of themes, which can be downloaded and used in a variety of ways as a source of evidence to enable understanding of the lived experience of ME/CFS and so contribute to the development of a more patient-focused research agenda in ME/CFS. CONCLUSIONS: While patient-based evidence used in the PRIME Project provides a useful start, further work is required to develop this area conceptually and methodologically, particularly in relation to how patient-based evidence can be considered alongside clinical and economic evidence. PMID- 20579120 TI - Is patient involvement during hospitalization for acute myocardial infarction associated with post-discharge treatment outcome? An exploratory study. AB - OBJECTIVE: To investigate whether patient involvement during hospitalization for acute myocardial infarction (MI) was associated with health and behavioural outcomes 6-10 weeks after hospital discharge. BACKGROUND: Patient involvement has been associated with improved health outcomes in chronic disease, but less research has focused on the effects of patient involvement in acute conditions, such as MI. DESIGN: Self-administered questionnaire study. Questionnaire results were run against medical outcome data in a national database of cardiac patients. SETTING AND PARTICIPANTS: Cardiac patients (n = 591) on their first follow-up visit after hospitalization for MI at 11 Swedish hospitals. MAIN OUTCOME MEASURES: Patient ratings of three questionnaire scales related to involvement; cardiovascular symptoms, medication compliance, participation in cardiac rehabilitation, and achievement of secondary preventive goals. RESULTS: More positive patient ratings of involvement were significantly associated with fewer cardiovascular symptoms 6-10 weeks after hospital discharge. In contrast, patients who attended cardiac rehabilitation and achieved the goals for smoking cessation and systolic blood pressure were significantly less satisfied with their involvement. No association was found between involvement ratings and medication compliance. CONCLUSION: This study represents a first attempt to examine associations between patient involvement in the acute phase of illness and short-term health outcomes. Some significant associations between involvement and health and behavioural outcomes after acute MI were found. However, higher involvement ratings were not consistently associated with more desirable outcomes, and involvement during hospitalization was not associated with MI patient health and behaviour 6-10 weeks after hospital discharge to the extent hypothesized. PMID- 20579121 TI - Shared decision making in oncology: assessing oncologist behaviour in consultations in which adjuvant therapy is considered after primary surgical treatment. AB - INTRODUCTION: Shared decision making (SDM) is now considered a desirable goal in health care, yet little is known about current practice in cancer care, and its impact on patient outcomes. This study aimed to develop an oncology-specific coding system for SDM, explore variations in SDM according to patient and disease characteristics, determine the relationship between SDM and patient satisfaction with the consultation, and explore the impact of SDM on patient anxiety. METHODS: Sixty-three medical and radiation oncology consultations with patients with primary cancer involving consideration of adjuvant therapy after surgery were audio-taped, transcribed and coded. Intra and inter-rater reliability of the coding system was 95 and 90% respectively. Patients completed questionnaires before and after the consultation. RESULTS: Construct validity of the SDM coding system was successfully conducted. Oncologists demonstrated on average under 11 of 18 SDM behaviours. Behaviours seeking patient preferences were particularly rare. SDM behaviours were more apparent in consultations involving female breast cancer patients. SDM behaviour scores in combination with patient involvement preference could predict achievement of patient involvement preference but not overall patient satisfaction. Although there was no overall relationship between patient anxiety and SDM scores, it did appear that physicians may change SDM behaviour according to patient factors including anxiety. CONCLUSION: Our findings reinforce the importance of the doctor in facilitating shared decision making in oncology consultations. PMID- 20579122 TI - Confirmatory factor analysis and recommendations for improvement of the Autonomy Preference-Index (API). AB - OBJECTIVE: Validation of the German version of the Autonomy-Preference-Index (API), a measure of patients' preferences for decision making and information seeking. METHODS: Stepwise confirmatory factor analysis was conducted on a sample of patients (n = 1592) treated in primary care for depression (n = 186), surgical and internal medicine inpatients (n = 811) and patients with minor trauma treated in an emergency department (n = 595). An initial test of the model was done on calculation and validation halves of the sample. Both local and global indexes-of fit suggested modifications to the scale. The scale was modified and re-tested in the calculation sample and confirmed in the validation sample. Subgroup analyses for age, gender and type of treatment setting were also performed. RESULTS: The confirmatory analysis led to a modified version of the API with better local and global indexes-of-fit for samples of German-speaking patients. Two items of the sub-scale, 'preference for decision-making', and one item of the sub-scale, 'preference for information seeking', showed very low reliability scores and were deleted. Thus, several global indexes-of-fit clearly improved significantly. The modified scale was confirmed on the validation sample with acceptable to good indices of fit. Results of subgroup analyses indicated that no adaptations were necessary. DISCUSSION AND CONCLUSIONS: This first confirmatory analysis for a German-speaking population showed that the API was improved by the removal of several items. There were theoretically plausible explanations for this improvement suggesting that the modifications might also be appropriate in English and other language versions. PMID- 20579124 TI - Patient organizations in Finland: increasing numbers and great variation. AB - OBJECTIVE: There is very little research on patient organizations (POs), even though their numbers and influence seem to be increasing. The purpose of this study was to describe the establishment, membership, size, organization, decision making and basic funding of national POs in Finland. SETTING AND PARTICIPANTS: National POs (n = 130) were identified from their umbrella organizations and by Internet searches. Data were collected from POs' web pages (87% of POs had one), Finland's Slot Machine Association (RAY, an important public financier of POs), a relevant survey done by a local TV-company, and interviews and written materials of POs. RESULTS AND CONCLUSIONS: Some current national POs were established around the turn of the 19(th) century. The rate of establishment of new POs increased from the 1970s and particularly in the 1990s when POs were characterized by increasing specialization. POs focused on different patient groups and diseases and were founded by philanthropists, physicians, patients, parents and the drug industry. Members could be patients, patient relatives, health-care professionals and organizations. POs widely varied in memberships (20 145 000, in 2002) and in number of paid personnel (0-1395, in 2002), organizational structure and decision making. Interest groups and financiers were often represented in decision-making organs. Activities included mutual support and service production, and, increasingly, informing and lobbying. POs had wide domestic and international co-operation and networking. Drug industry marketing was visible on PO web pages. Budget sizes varied (4000-15 million euros, in 2001). The main public financier was RAY. The old national POs were large and part of national social and health care, but newer ones were often established for mutual support and lobbying. National POs are not uniform but characterized by great variation. The number of national POs is increasing suggesting tighter competition for financing and visibility in the future. PMID- 20579123 TI - Understanding surgery choices for breast cancer: how might the Theory of Planned Behaviour and the Common Sense Model contribute to decision support interventions? AB - OBJECTIVE: To describe the evidence about factors influencing breast cancer patients' surgery choices and the implications for designing decision support in reference to an extended Theory of Planned Behaviour (TPB) and the Common Sense Model of Illness Representations (CSM). BACKGROUND: A wide range of factors are known to influence the surgery choices of women diagnosed with early breast cancer facing the choice of mastectomy or breast conservation surgery with radiotherapy. However, research does not always reflect the complexities of decision making and is often atheoretical. A theoretical approach, as provided by the CSM and the TPB, could help to identify and tailor support by focusing on patients' representations of their breast cancer and predicting surgery choices. DESIGN: Literature search and narrative synthesis of data. SYNTHESIS: Twenty-six studies reported women's surgery choices to be influenced by perceived clinical outcomes of surgery, appearance and body image, treatment concerns, involvement in decision making and preferences of clinicians. These factors can be mapped onto the key constructs of both the TPB and CSM and used to inform the design and development of decision support interventions to ensure accurate information is provided in areas most important to patients. CONCLUSIONS: The TPB and CSM have the potential to inform the design of decision support for breast cancer patients, with accurate and clear information that avoids leading patients to make decisions they may come to regret. Further research is needed examining how the components of the extended TPB and CSM account for patients' surgery choices. PMID- 20579125 TI - The Hospital Compare mortality model and the volume-outcome relationship. AB - OBJECTIVE: We ask whether Medicare's Hospital Compare random effects model correctly assesses acute myocardial infarction (AMI) hospital mortality rates when there is a volume-outcome relationship. DATA SOURCES/STUDY SETTING: Medicare claims on 208,157 AMI patients admitted in 3,629 acute care hospitals throughout the United States. STUDY DESIGN: We compared average-adjusted mortality using logistic regression with average adjusted mortality based on the Hospital Compare random effects model. We then fit random effects models with the same patient variables as in Medicare's Hospital Compare mortality model but also included terms for hospital Medicare AMI volume and another model that additionally included other hospital characteristics. PRINCIPAL FINDINGS: Hospital Compare's average adjusted mortality significantly underestimates average observed death rates in small volume hospitals. Placing hospital volume in the Hospital Compare model significantly improved predictions. CONCLUSIONS: The Hospital Compare random effects model underestimates the typically poorer performance of low volume hospitals. Placing hospital volume in the Hospital Compare model, and possibly other important hospital characteristics, appears indicated when using a random effects model to predict outcomes. Care must be taken to insure the proper method of reporting such models, especially if hospital characteristics are included in the random effects model. PMID- 20579126 TI - A randomized trial comparing mail versus in-office distribution of the CAHPS Clinician and Group Survey. AB - OBJECTIVE: To assess the effect of survey distribution protocol (mail versus handout) on data quality and measurement of patient care experiences. DATA SOURCES/STUDY SETTING: Multisite randomized trial of survey distribution protocols. Analytic sample included 2,477 patients of 15 clinicians at three practice sites in New York State. DATA COLLECTION/EXTRACTION METHODS: Mail and handout distribution modes were alternated weekly at each site for 6 weeks. PRINCIPAL FINDINGS: Handout protocols yielded an incomplete distribution rate (74 percent) and lower overall response rates (40 percent versus 58 percent) compared with mail. Handout distribution rates decreased over time and resulted in more favorable survey scores compared with mailed surveys. There were significant mode physician interaction effects, indicating that data cannot simply be pooled and adjusted for mode. CONCLUSIONS: In-office survey distribution has the potential to bias measurement and comparison of physicians and sites on patient care experiences. Incomplete distribution rates observed in-office, together with between-office differences in distribution rates and declining rates over time suggest staff may be burdened by the process and selective in their choice of patients. Further testing with a larger physician and site sample is important to definitively establish the potential role for in-office distribution in obtaining reliable, valid assessment of patient care experiences. PMID- 20579127 TI - Are lower response rates hazardous to your health survey? An analysis of three state telephone health surveys. AB - OBJECTIVE: To examine the impact of response rate variation on survey estimates and costs in three health telephone surveys. DATA SOURCE: Three telephone surveys of noninstitutionalized adults in Minnesota and Oklahoma conducted from 2003 to 2005. STUDY DESIGN: We examine differences in demographics and health measures by number of call attempts made before completion of the survey or whether the household initially refused to participate. We compare the point estimates we actually obtained with those we would have obtained with a less aggressive protocol and subsequent lower response rate. We also simulate what the effective sample sizes would have been if less aggressive protocols were followed. PRINCIPAL FINDINGS: Unweighted bivariate analyses reveal many differences between early completers and those requiring more contacts and between those who initially refused to participate and those who did not. However, after making standard poststratification adjustments, no statistically significant differences were observed in the key health variables we examined between the early responders and the estimates derived from the full reporting sample. CONCLUSIONS: Our findings demonstrate that for the surveys we examined, larger effective sample sizes (i.e., more statistical power) could have been achieved with the same amount of funding using less aggressive calling protocols. For some studies, money spent on aggressively pursuing high response rates could be better used to increase statistical power and/or to directly examine nonresponse bias. PMID- 20579128 TI - Effects of mass media coverage on timing and annual receipt of influenza vaccination among Medicare elderly. AB - OBJECTIVE: To measure the association between mass media coverage on flu-related topics and influenza vaccination, regarding timing and annual vaccination rates, among the nationally representative community-dwelling elderly. DATA SOURCE: Years 1999, 2000, and 2001 Medicare Current Beneficiary Survey. STUDY DESIGN: Cross-sectional survival analyses during each of three influenza vaccination seasons between September 1999 and December 2001. The outcome variable was daily vaccine receipt. We measured daily media coverage by counting the number of television program transcripts and newspaper/wire service articles, including keywords of influenza/flu and vaccine/shot shortage/delay. All models' covariates included three types of media, vaccine supply, and regional/individual factors. PRINCIPAL FINDINGS: Influenza-related reports in all three media sources had a positive association with earlier vaccination timing and annual vaccination rate. Four television networks' reports had most consistent positive effects in all models, for example, shifting the mean vaccination timing earlier by 1.8-4.1 days (p<.001) or increasing the annual vaccination rate by 2.3-7.9 percentage points (p<.001). These effects tended to be greater when reported in a headline rather than in text only and if including additional keywords, for example, vaccine shortage/delay. CONCLUSIONS: Timing and annual receipt of influenza vaccination appear to be influenced by media coverage, particularly by headlines and specific reports on shortage/delay. PMID- 20579129 TI - FOXP1 protein overexpression is associated with inferior outcome in nodal diffuse large B-cell lymphomas with non-germinal centre phenotype, independent of gains and structural aberrations at 3p14.1. AB - AIMS: To determine the molecular epidemiology and prognostic importance of structural and numeric FOXP1 gene aberrations with respect to BCL-6 gene and to FOXP1 protein expression in 389 diffuse large B-cell lymphomas (DLBCL) from the pre-rituximab era on tissue microarrays. METHODS AND RESULTS: By interphase fluorescence in situ hybridization with colour-labelled bacterial artificial chromosome clones, 12% (27/223) analysable cases showed FOXP1 gains and 1% (2/210) FOXP1 breaks. Seven percent of cases with known BCL-6 and FOXP1 gene status (n = 159) showed an isolated FOXP1 gain, 19% an isolated BCL-6 gain and 18% a trisomy 3. FOXP1 gains (isolated and due to trisomy 3) were more frequent in nodal than extranodal DLBCL and in non-germinal centre B-cell-like (non-GCB) DLBCL than in GCB DLBCL. By immunohistochemistry, FOXP1 protein was more often overexpressed in non-GCB than in GCB cases. FOXP1 overexpression was associated with poor disease-specific survival in all DLBCL, particularly in nodal and non GCB cases. There was no correlation between FOXP1 gene aberrations and either FOXP1 protein expression or survival. CONCLUSIONS: FOXP1 is recurrently targeted by numeric, and rarely by structural, genetic aberrations in DLBCL. Only the presence of FOXP1 protein, irrespective of its gene status, is decisive for prognosis in DLBCL. PMID- 20579130 TI - Biomarkers in bladder cancer. AB - Cancer biomarkers provide an opportunity to diagnose tumours earlier and with greater accuracy. They can also identify those patients most at risk of disease recurrence and predict which tumours will respond to different therapeutic approaches. Such biomarkers will be especially useful in the diagnosis and management of bladder cancer. At present, bladder tumours are diagnosed and followed-up using a combination of cystoscopic examination, cytology and histology. These are not only expensive, but also highly subjective investigations and reveal little about the underlying molecular characteristics of the tumour. In recent years numerous diagnostic and prognostic biomarkers of bladder cancer have been identified. Two separate approaches to biomarker discovery have been employed. The first is hypothesis-driven and focuses upon proteins involved in molecular pathways known to be implicated in tumorigenesis. An alternative approach has been to study the global expression of genes (so called 'genomics') looking for characteristic signatures associated with disease outcomes. In this review we summarize the current state of biomarker development in this field, and examine why so few have made the successful transition into the clinic. Finally, we introduce a novel approach to biomarker development utilizing components of the DNA replication licensing machinery. PMID- 20579131 TI - Diffusion-controlled reference material for VOC emissions testing: proof of concept. AB - Because of concerns about indoor air quality, there is growing awareness of the need to reduce the rate at which indoor materials and products emit volatile organic compounds (VOCs). To meet consumer demand for low emitting products, manufacturers are increasingly submitting materials to independent laboratories for emissions testing. However, the same product tested by different laboratories can result in very different emissions profiles because of a general lack of test validation procedures. There is a need for a reference material that can be used as a known emissions source and that will have the same emission rate when tested by different laboratories under the same conditions. A reference material was created by loading toluene into a polymethyl pentene film. A fundamental emissions model was used to predict the toluene emissions profile. Measured VOC emissions profiles using small-chamber emissions tests compared reasonably well to the emissions profile predicted using the emissions model, demonstrating the feasibility of the proposed approach to create a diffusion-controlled reference material. PRACTICAL IMPLICATIONS: To calibrate emissions test chambers and improve the reproducibility of VOC emission measurements among different laboratories, a reference material has been created using a polymer film loaded with a representative VOC. Initial results show that the film's VOC emission profile measured in a conventional test chamber compares well to predictions based on independently determined material/chemical properties and a fundamental emissions model. The use of such reference materials has the potential to build consensus and confidence in emissions testing as well as 'level the playing field' for product testing laboratories and manufacturers. PMID- 20579132 TI - Sources and migration of volatile organic compounds in mixed-use buildings. AB - We examined concentrations and migration of volatile organic compounds (VOCs) in ten mixed-use buildings in southeast Michigan, USA. In an office and work zone in each building, air exchange rates (AERs) were measured using perfluorocarbon tracers, and over 96 VOC species were measured by GC/MS over a 7-day period. VOCs were then apportioned to sources in offices, work zones, and outdoors using a two zone mass balance model. AERs averaged 3.9 h (0.2-14.2 h) in offices and 1.9 h (0.4-3.5 h) in work zones. The dominant VOCs included aromatics, terpenes and alkanes. VOC concentrations were uniform in the smaller spaces, and more variable in some of the very large spaces. Apportionments depended on the VOC and building, but emissions in industrial zones of buildings often migrated to office areas where they frequently accounted for the bulk of VOC concentrations. Outdoor sources accounted for most benzene and carbon tetrachloride, and a small fraction of aromatic and aliphatic compounds. This study shows that pollutant migration can be a significant and not uncommon problem in mixed-use buildings, and it demonstrates the need for better control of emissions and pollutant migration. PRACTICAL IMPLICATIONS: Pollutant exposures in industrial, commercial, and institutional buildings arise from indoor and outdoor sources that can be identified, apportioned, and controlled with knowledge of emission sources and building airflows. We show that multi-tracer techniques are an effective and practical means of determining airflows and exchange rates in large buildings. In examining a set of mixed-use buildings, a substantial fraction of VOC exposures in otherwise relatively 'clean' offices is due to pollutant migration from 'dirty' zones of the building. This indicates the need for corrective actions to minimize exposures of office workers that are unwanted and probably unknown to building managers. These actions should include better control of emissions, isolation or control of air and pollutant flows between building zones, and documentation of the effectiveness of such measures when strong emission sources are present. PMID- 20579133 TI - A laboratory evaluation of the physical and mechanical properties of selected root canal sealers. AB - AIM: To evaluate and compare the porosity, degree of conversion (DC) and hardness of two resin-based sealers; RealSeal and EndoRez, and a silicon-based sealer; GuttaFlow to that of a traditional zinc oxide-based sealer; TubliSeal. METHODOLOGY: For porosity, four samples from each sealer were prepared and scanned using a SkyScan 1072 Micro-CT. Porosity was then calculated using specialized software. For DC, 10 samples from each sealer were prepared and placed onto a Fourier transform infrared spectroscopy spectrometer. Spectra readings were carried out before and after curing of the sealers, and the DC for each sealer was calculated. For hardness, 10 samples from each sealer were prepared and then tested using a Wallace hardness tester. SPSS software was used for statistical analysis of the data using one-way anova and independent t-tests. RESULTS: TubliSeal had the highest percentage porosity (3.52%), whilst RealSeal had the lowest percentage porosity (0.41%). Statistically significant differences (P = 0.01) in porosity were present between all groups except between RealSeal and EndoRez groups. RealSeal exhibited a significantly higher DC% than EndoRez (P = 0.01), whereas EndoRez had the highest hardness number [28.54 Vickers hardness number (VHN)] whilst TubliSeal showed the lowest (13.57 VHN). Statistically significant differences in hardness were found between all groups (P = 0.01) except between RealSeal and EndoRez groups. CONCLUSIONS: Resin-based sealers had less porosity, greater hardness and a high DC. PMID- 20579134 TI - Ytterbium trifluoride as a radiopaque agent for dental cements. AB - AIM: To evaluate the radiopacity, degree of conversion (DC) and flexural strength of an experimental dental cement, with several added radiopaque substances. METHODOLOGY: Titanium dioxide, quartz, zirconia, bismuth oxide, barium sulphate and ytterbium trifluoride were added to the experimental cement in five different concentrations. Radiopacity was evaluated with a phosphor plate system, and the radiodensity of specimens was compared with an aluminium step-wedge. DC was evaluated with FT-infrared spectroscopy following 20 s of photo-activation. Specimens with dimensions of 12 x 2 x 2 mm were used for the flexural strength test. Data were analysed with two-way anova and Tukey's post hoc test. RESULTS: Radiopacity of the experimental dental cements with barium sulphate and bismuth oxide at 40% and ytterbium fluoride at 30% and 40% showed no significant differences in comparison with 3 mm of Al (181, 96). CONCLUSIONS: The experimental dental cements with at least 30% added ytterbium trifluoride had satisfactory radiopacity without influencing other properties. PMID- 20579135 TI - Varicocele correction for infertility: which patients to treat? AB - Given the lack of clarity regarding the value of varicocele correction in improving male fertility, we examined whether divergent results in this regard could be attributed to selection of patients, especially with regard to the duration of their infertility or to the length of patients' androgen receptor CAG repeats. In a prospective study, involving all varicocele patients consulted consecutively for infertility, we compared the pregnancy rate (PR) over 1 year produced by patients who opted not to have varicocele correction after extensive information concerning fertility prospects (N = 185), with that by patients who had varicocele correction (N = 137). In the second study involving another smaller group of varicocele subjects (N = 72), we investigated whether CAG repeat length in the androgen receptor gene had any influence on fertility of varicocele corrected patients. Overall, the PR in corrected and uncorrected varicocele groups did not differ significantly, but when subjects with infertility beyond 2 years were considered, varicocele-corrected subjects had a significantly greater PR than uncorrected varicocele patients (p = 0.025). Together with infertility duration, spermatozoa progressive motility appears the most important predictor of fertility, whereas neither grade of varicocele nor age of the couple (within the age limits of this study) influenced the outcome. Similarly, CAG repeat length did not affect the outcome of varicocele correction. These data suggest that varicocele correction at 1 year of infertility does not result in a significantly higher PR than that achieved by men with uncorrected varicocele. In view of the high spontaneous PR in subjects with an infertility of less than 2 years, varicocele correction aimed at restoring fertility appears to be most appropriate for men whose infertility extends beyond 2 years. PMID- 20579136 TI - Non-linear association between androgen receptor CAG repeat length and risk of male subfertility--a meta-analysis. AB - The CAG repeat in the androgen receptor (AR) has been widely studied in association with male infertility, but the results are conflicting. In a recent meta-analysis, infertile men had <1 repeat longer CAG stretch than fertile men when analysed in a linear regression model assuming that AR function diminishes with increasing CAG length. However, in vitro, a non-linear activity pattern was recently demonstrated so that ARs containing short and long stretches, respectively, displayed lower activity than the AR of median length. These results prompted us to explore the possible association between CAG number and male infertility risk in a stratified manner on the basis of data from the mentioned meta-analysis and subjects from our clinical unit. The study population included 3915 men, 1831 fertile and 2084 infertile. Data were divided into three categories: CAG<22, CAG 22-23 (reference) and CAG>23 and analysed in a binary logistic regression model. Men with CAG<22 and CAG>23 had 20% increased odds ratio of infertility compared with carriers of the median lengths [for CAG<22: p=0.03, 95% confidence interval (CI): 1.02-1.39; for CAG>23: p=0.02, 95% CI: 1.03 1.44]. These results show that an alternative model to a linear one for the genotype-phenotype association in relation to AR CAG repeats is likely, as lengths close to the median confine lowest risk of infertility. PMID- 20579137 TI - Medical treatment of benign prostatic hyperplasia: physician and patient preferences and satisfaction. AB - Practice guidelines acknowledge the importance of patient preferences in determining the appropriate treatment of benign prostatic hyperplasia (BPH). Recent literature suggests that patient and physician perspectives and satisfaction with BPH treatment management may differ; this may have an impact on clinical outcomes and patient compliance. This review evaluates patients' and physicians' preferred treatment options for managing BPH and patient satisfaction with therapy. A Medline-based systematic review using the terms 'Benign prostatic hyperplasia' + 'Patient preference/perception/satisfaction' or 'Physician/urologist preference/perception' was performed. Patients prefer therapies affecting long-term disease progression over those that provide short term symptom improvement, which contrasts with the beliefs of their physicians. The prescribing behaviour of urologists and primary care physicians can be very varied. Studies of patient satisfaction with specific treatments generally show a high level of overall satisfaction, but cross-study comparisons are limited because of heterogeneity in study design. The evidence to date suggests that patients' views and beliefs and those of their physician may not always be in agreement. Improved physician-patient communication will help determine the best treatment option for patients with BPH and may ensure greater compliance and treatment success. PMID- 20579138 TI - Assessing patients' descriptions of lower urinary tract symptoms (LUTS) and perspectives on treatment outcomes: results of qualitative research. AB - AIMS: Understanding the patient's experience and symptom descriptions is critical to assess outcomes. Thus, there is a need for qualitative research to better understand how patients describe their symptoms and treatment expectations. METHODS: Eight focus groups were conducted in two research phases: Phase 1 focused on eliciting patient's descriptions of urinary symptoms, and Phase 2 assessed patient perspectives on treatment outcomes. Participants with a range of lower urinary tract symptoms (LUTS) were recruited from urology clinics and community settings in the United States. All interviews were audio recorded and transcribed. Content and descriptive analyses were performed. RESULTS: A total of 33 men and 30 women participated. Mean ages for men and women were 55 and 61 in Phase 1, and 57 and 61 in Phase 2, respectively. About 73% of participants were white people, and most had a high school education or greater. A wide range of LUTS were emergently described, and the words, concepts and phrases were generally similar across groups. Most participants identified with the word 'bother', and thought it was important to assess both the frequency and bother of each symptom. Reasons for seeking care included symptom bother and fears about cancer and bladder infections. Most participants thought that a 50% improvement in a single symptom or group of symptoms would be a meaningful treatment outcome. CONCLUSION: This qualitative research provides a better understanding on how men and women describe their LUTS and their perspectives on treatment outcomes. This research can be used to inform the development of a new LUTS outcomes' tool. PMID- 20579139 TI - Expression of the reversion-inducing cysteine-rich protein with Kazal motifs and matrix metalloproteinase-14 in neuroblastoma and the role in tumour metastasis. AB - Neuroblastoma is the most common malignant tumour in infancy; the reversion inducing cysteine-rich protein with Kazal motifs gene (RECK) is a tumour suppressor gene. Previous studies show that RECK inhibits tumour invasion and metastasis through negative regulation of the matrix metalloproteinase (MMP)-2, MMP-9 and MMP-14. Therefore, we wanted to detect the expression of RECK and MMP 14 in neuroblastomas to assess the correlation between the expression levels of these proteins, and to investigate the roles in the metastasis and development of the tumour. PV-6000 immunohistochemistry method was used to detect the expression levels of RECK and MMP-14 in 36 samples of neuroblastoma tissue. Samples from paraffin wax-embedded specimens and the complete clinicopathological data of 36 neuroblastoma and 10 ganglioneuroma patients were collected. The rate of expression of the RECK protein in the neuroblastoma was low (16.7%). Furthermore, it reduced with the increase in the invasive depth and distant metastasis (P = 0.015; P < 0.05). The rate of expression of the MMP-14 protein in the neuroblastoma was high (58.3%) and increased with the increase in the extent of invasive depth and distant metastasis (P = 0.002; P < 0.05). The expression of the RECK protein correlated negatively with that of MMP-14 (r = -0.418; P < 0.05). Low levels of the RECK protein are expressed in the neuroblastoma, while the MMP-14 protein is expressed at high levels. The RECK and MMP-14 proteins may serve as markers in the estimation of the extent of metastasis and dissemination of the neuroblastoma. PMID- 20579140 TI - Abstracts of the XXIII International Symposium on Technological Innovations in Laboratory Hematology. May 10-12, 2010. Brighton, United Kingdom. PMID- 20579141 TI - Abstracts of the 14th Congress of Asia Pacific League of Associations for Rheumatology. July 11-15, 2010. Hong Kong. PMID- 20579142 TI - Reproductive health needs to be front and centre in development. PMID- 20579144 TI - Shaping the future: role models and situated learning. PMID- 20579143 TI - Nursing and disaster preparedness. PMID- 20579149 TI - Evaluation of patient self-management outcomes in health care: a systematic review. AB - BACKGROUND: The importance of self-management and its intervention for improving the ability and skill of self-management has been discussed in literatures. It is, however, unclear how to choose the fitted, objective and accurate evaluation system when assessing the outcome. AIM: The aim of this article was to establish a general evaluation system for skill and ability of self-management in chronic diseases through systematic review on different evaluation indicators and scales. METHOD: A systematic search of six electronic databases was conducted. Two authors independently reviewed each qualified study for relevance and significance. Subsequently, main evaluation indicators and scales were identified and categorized into themes and sub-themes. RESULTS: Nineteen articles were identified in this review. Among them, six main evaluation indicators of self management, including frequently used scales, were extracted and tabulated. Self efficacy, health behaviour/attitude, health status, health service utilization, quality of life and psychological indicators were the main indicators in evaluating self-management outcome, and they could be used alone or in combination flexibly according to the different goals of programmes. CONCLUSION: Accurate evaluation of skill and ability of self-management is crucial not only in baseline data collection but also in proving the effectiveness of intervention. The outcomes of this study provide future researchers or caregivers with a better understanding and a series of good choices in self-management outcome evaluation. PMID- 20579150 TI - Presence of nursing information on hospital websites in five countries: a review. AB - AIM: The aims of this study were to (1) examine the presence of nursing information on 50 hospital websites across five countries; (2) describe the accessibility, range and depth of nursing information provided; and (3) compare the characteristics of nursing web information across the countries. BACKGROUND: Providing information on hospital website is an increasingly popular strategy for marketing hospital services, and it has been playing unique and important roles for nursing. So far, the nursing information offered via hospital websites is not uncommon worldwide, but the amount, content and form of such information presented by the institutions of different countries have not been examined systematically. METHODS: Objective sampling was employed to select 50 top hospital websites from five countries, with ten for each geographical region, namely, Australia (Oceania), China (Asia), South Africa (Africa), UK (Europe) and the USA (North America). A self-developed checklist was used to examine the presence of nursing information on the above-mentioned hospital websites. FINDINGS: The most frequently presented information on the hospital websites was nursing employment (job placement), nursing education, and news and events concerning the nursing profession, but information about other aspects of nursing was relatively lacking. The hospital websites in the USA and Australia provided more information as compared with those in China and the UK. Nursing information was almost unavailable on hospital websites in South Africa. Although the accessibility of nursing-related information has been improved, the presence of nursing information was not strong on the hospital websites across the five countries. CONCLUSION: The nursing information presented on hospital websites varied with different countries. Efforts have to be made to improve the presence and accessibility of nursing information. Information about the nursing services, professional image of nurses and nursing employment should be enhanced. PMID- 20579151 TI - Global Government Health Partners' Forum 2006: eighteen months later. AB - BACKGROUND: The challenge of global health worker shortages, particularly among nurses, has been the topic of numerous forums over the last several years. Nevertheless, there has been little attention given to the roles of government chief nursing and medical officers as key partners in addressing health worker shortages. This partnership and its potential impact on the adequacy of the global health workforce was the focus of the most recent Global Government Health Partners (GGHP) Forum held in November 2006 in Atlanta, Georgia, USA. This forum was uniquely designed to create a context for government chief nursing officers and chief medical officers to engage in a joint learning and planning experience focused on positioning their leadership to impact health workforce issues. AIM: This article describes an 18-month follow-up evaluation of the outcomes of the GGHP. The purpose of the evaluation was to assess the impact of the forum experience on the actions of participants based on the country-level plans they produced at the forum. This important feedback is intended to inform the design of future partnered global forums and gain insights into the utility of forum based action plans. The evaluation process itself has served as an opportunity for the engagement of university faculty, students and staff in a global service learning experience. CONCLUSION: The outcomes of this evaluation indicate that important progress has been made by countries whose leadership was involved in the forum, and was also an important learning activity for those participating in the conduct of the study. PMID- 20579152 TI - Collaborative nursing leadership project in the People's Republic of China. AB - BACKGROUND: A nursing leadership project for directors of nursing (DONs) in China was implemented by the Ministry of Health, Peking Union Medical College, School of Nursing; Chinese Nurses' Association and University of California, San Francisco, School of Nursing. AIMS: The aims were: (1) to establish a leadership project, (2) to survey DONs on the perceived importance of role competencies, and (3) to develop an education program. METHODS: A survey was completed by the DONs on the importance of role competencies related to the forces of magnetism. The DONs rated their job satisfaction. Four leadership educational modules were developed. FINDINGS: The 28-item survey was completed by 208 (68%) DONs from public tertiary hospitals who rated each item on a six-point Likert scale. The mean scores of the items ranged from 4.29 [standard deviation (SD) 1.21] to 5.66 (SD 0.70), suggesting they felt that most were very important. DONs who reported higher job satisfaction perceived two dimensions of the forces (structural empowerment and exemplary professional practice) as significantly more important than those with lower job satisfaction. The greatest work challenge reported was shortage of nurses. The four educational modules were pilot tested with ten DONs in Beijing and they provided positive feedback. CONCLUSION: The DONs perceived that the forces of magnetism competencies were important to their work settings in China. The modules were positively received and plans are underway to develop a train-the-trainer program. STUDY LIMITATIONS: While the instrument was developed for this study, the validity and reliability were demonstrated. PMID- 20579153 TI - Associations between work schedule characteristics and occupational injury and illness. AB - BACKGROUND: Nurses often endure working irregular day, night and evening shifts as well as mandatory overtime (i.e. employer-imposed work time in excess of one's assigned schedule). While these work characteristics are examined as potential risks for nurses' safety and health, it is not clear whether negative health impacts occur simply because of working long hours or in combination with other mechanisms. AIM: This study investigates how these work characteristics are associated with nurses' work-related injury and illness over and above long work hours. METHODS: In this cross-sectional study, questionnaire data were collected from a sample of 655 registered nurses in the Philippines. Multiple logistic regression was used to assess associations of shift work and mandatory overtime with four work-related health outcomes. RESULTS: After weekly work hours, shift length and demographic variables were accounted for, non-day shifts were associated with work-related injury [odds ratio (OR) = 1.54; 95% confidence interval (CI): 1.07, 2.24] and work-related illness (OR = 1.48; 95% CI: 1.02, 2.16). Also, frequency of working mandatory overtime was associated with work related injury (OR = 1.22; 95% CI: 1.06, 1.41), work-related illness (OR = 1.19; 95% CI: 1.04, 1.37) and missing more than 2 days of work because of a work related injury or illness (OR = 1.25; 95% CI: 1.08, 1.44). CONCLUSIONS: These findings suggest that non-day shifts and mandatory overtime may negatively impact nurses' health independent of working long hours. Mechanisms through which these work characteristics affect health, such as circadian rhythm disturbance, nurse to-patient ratios and work-family conflict, should be examined in future studies. PMID- 20579154 TI - Work and non-work social support and intent to stay at work among Jordanian hospital nurses. AB - PURPOSE: To examine (1) the level of intent to stay at work among Jordanian nurses; (2) the levels of at-work and non-work social support; and (3) the extent of variance in the level of intent to stay at work because of the demographic and social support variables. DESIGN: A survey design was used to investigate the predictors of intent to stay at work among the population of Jordanian nurses in three public hospitals. Two hundred and seventy five participants submitted complete and usable questionnaires. The response rates were 50%, 55% and 70%, respectively. METHODS: Data were collected using a questionnaire that included a scale for measuring social support, the McCain's Intent to Stay Scale and the demographic form. FINDINGS: The results showed that support from supervisors, marital status, number of friends at work, number of children at home, gender, time commitment, support from co-workers and support from family accounted for 60% of the variation in the level of intent to stay. The results indicated that nurses who were females, had children at home, worked full time and perceived having more support from co-workers and supervisors tended to stay at work more than others. On the other hand, the results showed that marital status, number of friends at work and family support were associated negatively with intent to stay at work. CONCLUSION: The findings of the study suggest the important role of workplace social support in enhancing the level of intent to stay at work. PMID- 20579155 TI - Growing together: a qualitative study of leading nurse scholars in Thailand. AB - BACKGROUND: Asia-Pacific nursing education and research is growing but little is known about the nature and development of nursing scholarship in the region. AIM: This qualitative study explored the perspectives of 14 leading Thai scholars about the development, facilitators and barriers relating to Thailand's nursing scholarship. METHOD: In-depth interviews were digitally recorded, and data were subjected to content analysis. FINDINGS: Five themes arose: (1) growing together, (2) visionary leadership, (3) external support to grow nurse scholars, (4) developing nursing through research, and (5) barriers to scholarship. A history of visionary nursing leadership was revealed, underpinned by leaders' values of growing nursing together. Resource sharing among universities, and a significant number of scholarships for study abroad were major facilitators of scholarship growth. Barriers to scholarship included high teaching loads, especially for newly graduated faculty; a low rate of research publications; not enough mentorship for research and changes to teaching practice; and a wide range of different agencies providing courses for entry to practice. CONCLUSIONS: Scholarship development in Thailand is a role model for a number of South-East Asian countries, with inclusiveness and collaboration to facilitate the growth of nursing education inside and outside of the country as a hallmark of its character. However, against a backdrop of nursing shortages, Thai scholars are challenged, in the future, to produce meaningful research outcomes, including publications of studies; to collaborate with other health professionals; change practices to overcome high teaching loads; and provide the much needed mentorship for young scholars. PMID- 20579156 TI - Cancer incidence among male Danish nurses, 1980-2003. AB - BACKGROUND: The cancer risk of female nurses has been examined in several studies, but none has addressed the risk of male nurses, although they may be exposed to the same carcinogens as female nurses. In this register-based cohort study, we explored cancer incidence among male Danish nurses. METHODS: We identified 3369 male nurses from the files of the Danish Nurses Association and followed them up from 1980 to 2003 in the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated on the basis of standardized national rates. We compared the nurses with 3369 other male employees matched to the nurses by year of birth on social variables (vital and marital status). FINDINGS: We observed 90 cancers in the cohort, with significantly increased SIRs for sarcomas and decreased SIRs for cancers of the respiratory system. When the cohort was stratified by educational generation and birth cohort, we observed significantly elevated relative risks for cancers of the brain and nervous system among the youngest nurses and for sarcomas among nurses in all educational generations and those born between 1945 and 1954. CONCLUSION: The overall risk for cancer among male Danish registered nurses is similar to that of the general male Danish population. The high SIRs observed for cancers of the brain and nervous system merit further attention. The high relative risks for sarcomas and connective tissue tumours reflect a large proportion of cases of Kaposi sarcoma, which is probably not occupationally related. PMID- 20579157 TI - Chinese nurses' experience in the Wenchuan earthquake relief. AB - AIM: The purpose of this qualitative study is to provide an understanding of how Chinese nurses acted in response to the 2008 Wenchuan earthquake. BACKGROUND: The literature has reported that Chinese nurses played a key role in the Wenchuan earthquake. Although these nurses' intentions were well meaning, and they made enormous efforts to save lives, they considered that disaster relief practice was beyond the scope of normal daily nursing practice and found the challenges they confronted overwhelming. China is a country prone to both natural and man-made disasters that demand a good deal of preparedness for those involved in disaster nursing. However, few studies have been conducted to investigate the knowledge, skill, experience and attitudes required for nurses responding to disasters. METHODS: Gadamer's philosophical hermeneutics was used as a framework to underpin and interpret the qualitative accounts of the practice of the ten registered nurses in this study. FINDINGS: Three themes were identified from semi-structured interviews with the participants. These are described as (1) feeling under prepared; (2) perceived challenges and coping strategies; and (3) the rediscovery of the helping and caring role. By analysing these nurses' experiences in the Wenchuan earthquake relief operation, this study has identified the numerous roles and attributes required of nurses in response to disasters. CONCLUSION: Without education and training in disaster nursing, nurses may not be prepared to function in disaster relief, especially in a manner that is productive, efficient, collaborative and less stressful. Findings suggest that a systematic, educational approach to develop the skills required in disaster nursing is essential. PMID- 20579158 TI - Primary health care nurses' promotion of involuntary migrant families' health. AB - BACKGROUND: Involuntary migrant families in cultural transition face a number of challenges to their health and to family cohesion. Primary health care nurses (PHCNs) therefore play a vital role in the assessment and promotion of their health. AIM: The aim of this study was to describe the promotion of health in involuntary migrant families in cultural transition as conceptualized by Swedish PHCNs. METHOD: Interviews were conducted with 34 strategically chosen PHCNs covering the entire range of the primary health care sector in two municipalities of Southern Sweden. A contextual approach with reference to phenomenography was used in interpreting the data. FINDINGS: There are three qualitatively different descriptive categories epitomizing the characteristics of the PHCNs' promotion of health: (1) an ethnocentric approach promoting physical health of the individual, (2) an empathic approach promoting mental health of the individual in a family context, and (3) a holistic approach empowering the family to function well in everyday life. CONCLUSIONS: For nurses to promote involuntary migrant families'health in cultural transition, they need to adopt a holistic approach. Such an approach demands that nurses cooperate with other health care professionals and community authorities, and practise family-focused nursing; it also demands skills in intercultural communication paired with cultural self awareness in interacting with these families. Adequate knowledge regarding these skills should therefore be included in the education of nurses, both at under- and at post-graduate level. PMID- 20579159 TI - The evaluation of nurses and nursing activities through the perceptions of inpatients. AB - AIM: To examine the relationship of inpatients' perceptions and satisfaction statements with nurses and the nursing activities presented and to determine nursing activities that were implemented mostly from the view of inpatients. BACKGROUND: Nursing care is one of the fundamental components of health care, and studies have shown that it has a considerable influence on how patients experience hospitalization. However, nursing care is usually listed as one category in surveys. In fact, nursing care is an integrated combination of specific nursing activities, and to improve nursing practice we need to clarify how each nursing activity affects the perceptions of patients. METHODS: This descriptive study uses cross-sectional survey design. The sample consists of 454 inpatients from a large-scale teaching hospital in Ankara, Turkey. A questionnaire survey including demographics and perceptions of the patients, along with a list of the activities that nurses were required to carry out, were administered to the patients. FINDINGS: Age, gender and marital status were the variables influencing patients' perceptions. Technical nursing activities were recognized more by patients than activities related to care. All nursing activities were relevant to patient satisfaction statements. Most of the patients were satisfied with the nursing care despite the task-oriented environment. CONCLUSIONS: The results of this study show that nurses tend to do technical activities. All nursing activities were related to patient satisfaction statements. Nurses should be aware of the effect of each activity they are required to carry out on patients and the importance of good communication with patients. PMID- 20579160 TI - Evaluation of an elderly care training programme for women. AB - BACKGROUND: Caregiving across different cultures has been perceived conventionally as a private or family responsibility, predominantly performed by women who accept their caregiving as part of their gender role. AIM: This study aimed to design, deliver, and evaluate an elderly training programme for women by assessing their knowledge, attitudes and skills as a lay caregiver. Encouraging the women to find suitable positions for employment in private or governmental institutions was the further objective of the study. DESIGN: The study was a quasi-experimental one-group pre-test post-test design. METHODS: The study was conducted in a solidarity centre for women and in a nursing home for the elderly. The sample covered 120 women selected from the community by convenience sampling. Data were gathered through pre- and post-test evaluation and observation forms in 2 May-22 December 2005. The training programme consisted of 230 h of didactic sessions, demonstrations and clinical practices. FINDINGS: The mean change in the participants' knowledge score (pre-test: 41.44 +/- 0.92; post-test: 71.16 +/- 1.34) demonstrated a statistically significant improvement in their knowledge. According to clinical observations, most of them displayed satisfactory caring and communication skills towards the elderly. Virtually all participants reported increased skill, knowledge and confidence. CONCLUSION: The developed training programme was effective, resulting in an increased knowledge, the acquisition of good attitudes towards the elderly, and performing satisfactory caring and communication skills. Similar community-based programmes managed by nurses are recommended to support non-professional caregivers. The research is not only an innovative but also a revolutionary model to promote women. PMID- 20579161 TI - Life experiences after stroke among Iranian stroke survivors. AB - BACKGROUND: Stroke is a major cause of disability worldwide. It is a life threatening and life-altering event, which leaves many physical and mental disabilities, thus creating major social and economic burdens. Experiencing a stroke and its aftermath can be devastating for patients and their families. In Iran, many services are not available for those who lack property; this may result in many difficulties and long-term problems for stroke survivors and their family members who are usually the main caregivers in Iranian cultural. Despite its effect on their lives, little is known about how the survivors perceive stroke in the Iranian context, therefore, knowing more about this process may enhance problem identification and problem solving. AIM: To illuminate how stroke survivors experience and perceive life after stroke. METHOD: A grounded theory approach was recruited using semi-structured interviews with 10 stroke survivors. FINDINGS: The survivors perceived that inadequate social and financial support, lack of an educational plan, lack of access to rehabilitative services, physical and psychological problems led them to functional disturbances, poor socio economical situation and life disintegration. The core concept of life after stroke was functional disturbances. CONCLUSIONS: The study shows the need to support the stroke survivors in their coping process with their new situation by providing appropriate discharge plans, social and financial support, social insurances and training programmes for the stroke survivors and their families. PMID- 20579162 TI - Vasectomy within the public health services in Campinas, Sao Paulo, Brazil. AB - OBJECTIVE: To describe some of the characteristics of men who underwent a vasectomy in the public health network of Campinas, Sao Paulo, Brazil. METHODS: A descriptive study including 202 men randomly selected from a list of all the men vasectomized between 1998 and 2004 in the public health network. RESULTS: Most of the men were 30 years of age or older when vasectomized, had completed elementary school and had two or more children of both sexes. Most of the men came from the lowest income segment of the population: 47.6% in 1998-1999 and 61.3% in 2003 2004. Although the men knew various contraceptive methods, 51.2% reported that their partners were using combined oral contraceptives at the time of surgery. Most men initially sought information on vasectomy at health-care clinics where care was provided by a multidisciplinary team; most received counselling, however, 47.9% of the men waited more than 4 months for the vasectomy. CONCLUSIONS: The profile of the vasectomized men in this study appears to indicate that the low-income population from Campinas, Sao Paulo, Brazil has access to vasectomy; however, the waiting time for vasectomy reveals that difficulties exist in obtaining this contraceptive method in the public health service. PMID- 20579163 TI - Behaviours used by HIV-positive adolescents to prevent stigmatization in Botswana. AB - BACKGROUND: The increasing numbers of adolescents living with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) are a compelling public health issue, and interventions are more likely to be effective if developed from the perspective of those adolescents. Despite the prevalence of HIV in Botswana, stigmatization is a common occurrence. AIM: The purpose of this paper is to report on the findings of a study undertaken to describe adolescents' perceptions in Botswana on the behaviours that HIV-positive adolescents use in dealing with stigmatization. METHOD: Four focus group discussions were held with 18 adolescents. FINDINGS: Adhering to AIDS therapies, seeking early treatment for common conditions and keeping silent about their diagnosis were the major findings of the study. CONCLUSION: The findings have implications for both policy makers and health care practitioners. PMID- 20579164 TI - Development of community nursing in Zhejiang Province, China: a report of the driving measures. AB - BACKGROUND: Community nursing is playing an important role in health care worldwide. METHODS: We reviewed recent developments in community nursing in the Zhejiang province of China and reported that the locally tailored practical guidelines, education programmes and management models are the driving measures for promoting local community nursing. RESULTS: In 2008, Zhejiang had 1200 community primary health-care service centres, an increase of 56% and 6789 service stations, a twofold increase, compared with 2004. At present, 27 000 community nurses, together with the same number of family doctors, are working in community health-care service centres and stations. Community nursing in Zhejiang has grown not only by numbers but also by the greatly improved infrastructures and functions of its community primary health care. CONCLUSION: It is the multi pronged approach that has led to the change being successful in a local health care system. PMID- 20579165 TI - Depressive symptoms among community-dwelling, post-stroke elders in Hong Kong. AB - BACKGROUND: Depressive symptoms adversely affect functional recovery among post stroke elders. Such symptoms manifest when elders face difficulties in realistic daily living after being discharged. AIMS: The aim of this study was to examine (1) the prevalence of depressive symptoms among community-dwelling post-stroke elders, (2) the relationship between depressive symptoms and demographic and clinical characteristics among community-dwelling post-stroke elders, and (3) the demographic and clinical factors that differentiate post-stroke elders with and without depressive symptoms. METHODS: A descriptive cross-sectional survey was performed on 50 post-stroke elders from a geriatric day clinic. FINDINGS: Depressive symptoms were highly prevalent (68%) among the community-dwelling post stroke elders. Depressive symptoms were negatively correlated with social support network, social support satisfaction and functional independence. Lastly, poor social support satisfaction and lower functional independence was found to differentiate those post-stroke elders with and without depressive symptoms. CONCLUSION: The inclusion of psychosocial assessment and delivery of appropriate psychosocial interventions to post-stroke elders are recommended. PMID- 20579166 TI - Effect of situational and clinical variables on the likelihood of physicians ordering physical restraints. AB - OBJECTIVES: To model clinical and situational variables that may affect likelihood of physicians to order physical restraints. DESIGN: Cross-sectional, factorial survey. SETTING: One academic medical center. PARTICIPANTS: One hundred eighty-nine physicians: interns in all specialty practices and resident and attending physicians in departments of surgery, general internal medicine, family practice, emergency medicine, and psychiatry. MEASUREMENTS: Vignettes were randomly generated using different values of six situational and eight clinical variables. Each physician received five unique vignettes for which they indicated their likelihood to order restraint on a 10-point scale. RESULTS: Nine hundred six distinct vignettes were completed. The mean likelihood that physicians would order restraint was 3.9 + or - 3.0 (range 0 (not at all) to 9 (absolutely)). Exploratory regression analysis on physician's likelihood to restrain with independent variables of secondary diagnosis, patient age, sex, time of day, familiarity and trust with requesting nurse, patient behavior, vital signs, oxygen saturation, and dehydration explained 12.5% of variance (F=5.43, P<.001). Independent factors of unsafe patient behavior (P=.001) and secondary diagnosis of dementia (P=.06) resulted in greater likelihood of ordering restraint, whereas lack of trust in the judgment of the reporting nurse (P=.008) resulted in lower likelihood of ordering restraints. CONCLUSION: Patients' clinical status had less influence on physicians' likelihood of ordering physical restraints than the working relationship with the requesting nurse or the patient's behavior. Interdisciplinary team approaches with active physician input for nonrestraint strategies in the management of patient behavior is emphasized to minimize restraint use. PMID- 20579167 TI - Can agitated behavior of nursing home residents with dementia be prevented with the use of standardized stimuli? AB - OBJECTIVES: To assess the relative effect of different types of stimuli on agitated behaviors of nursing home residents with dementia. DESIGN: Repeated measures design with randomized assignment of conditions. SETTING: Seven Maryland nursing homes. PARTICIPANTS: One hundred eleven nursing home residents with a diagnosis of dementia who exhibited agitation. INTERVENTION: Different types of stimuli (music, social stimuli, simulated social stimuli, and individualized stimuli based on the person's self-identity) were presented. MEASUREMENTS: Agitation was directly observed and recorded using the Agitation Behavior Mapping Instrument. RESULTS: All stimulus categories were associated with significantly less physical agitation than baseline observations, and all except for manipulative stimuli were associated with significantly less total agitation. Live social stimuli were associated with less agitation than music, self identity, work, simulated social, and manipulative stimulus categories. Task and reading stimulus categories were each associated with significantly less agitation than work, simulated social, and manipulative stimulus categories. Music and self-identity stimuli were associated with less agitation than simulated social and manipulative stimuli. CONCLUSION: Providing stimuli offers a proactive approach to preventing agitation in persons with dementia, with live social stimuli being the most successful. PMID- 20579168 TI - Likelihood of ordering physical restraints: influence of physician characteristics. AB - OBJECTIVES: To determine physician knowledge regarding restraint regulations and effectiveness and effect of physician characteristics on likelihood of ordering restraints. DESIGN: Cross-sectional, factorial research survey. SETTING: Academic medical center. PARTICIPANTS: Interns in all specialties; residents in internal medicine, family practice, emergency medicine, psychiatry, and surgery; and attending faculty at an academic medical center. MEASUREMENTS: Survey of demographic, professional, and restraint knowledge items and for each of five distinct vignettes; physician ratings of probability of patient harm and likelihood of ordering restraints. For each, physicians rated probability of patient harm and likelihood of ordering restraint. RESULTS: One hundred eighty nine of 246 (77%) surveys were returned. More than half (58%) were men; the median age was 30 (range 25-63), median years experience was 2 (range 0-33), and 60% were U.S. medical school graduates. Mean knowledge score was 68.4% (range 27 100%). Mean likelihood of ordering restraints ranged from 0.6 (not likely) to 9 (absolutely) (overall mean 3.9 +/- 2.2). Exploratory hierarchical regression on mean likelihood of ordering restraint (outcome) with independent variables of physician age and sex (Step 1), years experience and physician level (Step 2), specialization (Step 3), restraint knowledge (Step 4), and judgment of harm (Step 5) explained 31.9% of the variance (F=7.19, degrees of freedom 13,159, P<.001). Higher appraisal of harm (P<.001), less knowledge regarding restraint (P=.03), and male sex (P=.005) were unique indicators for the likelihood of ordering restraints. Psychiatry (P=.03) or internal medicine physicians (P=.05) were less likely to order restraints. CONCLUSION: Physician characteristics and lack of restraint knowledge are associated with likelihood of ordering restraints. Results will guide medical education initiatives to reduce restraint rates. PMID- 20579169 TI - Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis. AB - OBJECTIVES: To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults. DESIGN: Systematic review and meta-analysis. SETTING: MEDLINE, CINAHL, Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies. PARTICIPANTS: Older adults (aged > or = 60) who participated in randomized controlled trials that both investigated the effectiveness of vitamin D therapy in the prevention of falls and used an explicit fall definition. MEASUREMENTS: Two authors independently extracted data, including study characteristics, quality assessment, and outcomes. The I(2) statistic was used to assess heterogeneity in a random-effects model. RESULTS: Of 1,679 potentially relevant articles, 10 met inclusion criteria. In pooled analysis, vitamin D therapy (200-1,000 IU) resulted in 14% (relative risk (RR)=0.86, 95% confidence interval (CI)=0.79-0.93; I(2)=7%) fewer falls than calcium or placebo (number needed to treat =15). The following subgroups had significantly fewer falls: community-dwelling (aged <80), adjunctive calcium supplementation, no history of fractures or falls, duration longer than 6 months, cholecalciferol, and dose of 800 IU or greater. Meta regression demonstrated no linear association between vitamin D dose or duration and treatment effect. Post hoc analysis including seven additional studies (17 total) without explicit fall definitions yielded smaller benefit (RR=0.92, 95% CI=0.87-0.98) and more heterogeneity (I(2)=36%) but found significant intergroup differences favoring adjunctive calcium over none (P=.001). CONCLUSION: Vitamin D treatment effectively reduces the risk of falls in older adults. Future studies should investigate whether particular populations or treatment regimens may have greater benefit. PMID- 20579171 TI - Hunter-Schreger Band patterns in human tooth enamel. AB - Using light microscopy, we examined Hunter-Schreger Band (HSB) patterns on the axial and occlusal/incisal surfaces of 160 human teeth, sectioned in both the buccolingual and mesiodistal planes. We found regional variations in HSB packing densities (number of HSBs per mm of amelodentinal junction length) and patterns throughout the crown of each class of tooth (maxillary and mandibular: incisor, canine, premolar, and molar) examined. HSB packing densities were greatest in areas where functional and occlusal loads are greatest, such as the occlusal surfaces of posterior teeth and the incisal regions of incisors and canines. From this it is possible to infer that the behaviour of ameloblasts forming enamel prisms during amelogenesis is guided by genetic/evolutionary controls that act to increase the fracture and wear resistance of human tooth enamel. It is suggested that HSB packing densities and patterns are important in modern clinical dental treatments, such as the bonding of adhesive restorations to enamel, and in the development of conditions, such as abfraction and cracked tooth syndrome. PMID- 20579170 TI - Leukocyte telomere length is associated with disability in older u.s. Population. AB - OBJECTIVES: To determine whether mean leukocyte telomere length (LTL) serves as a biomarker of disability assessed according to activities of daily living (ADLs) and what factors may modify this relationship. DESIGN: Retrospective cross sectional study. SETTING: A subset of the National Long Term Care Survey (NTLCS), a Medicare-based U.S. population longitudinal study focused on trends of overall health and functional status in older adults. PARTICIPANTS: Six hundred and twenty-four individuals from the 1999 wave of the NTLCS cohort. MEASUREMENTS: Relative LTL determined according to quantitative polymerase chain reaction. LTL has previously been shown to correlate with common age-related disorders and mortality, as well as with socioeconomic status. RESULTS: A sex difference in LTL was observed but not age-dependent shortening or association with socioeconomic status. LTL was associated with disability and functional status assessed according to ADLs. The association between ADLs and LTL was stronger in subjects without diabetes mellitus, whereas associations were not seen when only subjects with diabetes mellitus were analyzed. Associations between LTL and cardiovascular disease (CVD) and cancer were also present in the group without diabetes mellitus but not in the group with diabetes mellitus. CONCLUSION: These findings support the concept that LTL is a biomarker of overall well-being that is predictive of disability of older individuals in the U.S. population. Diabetes mellitus plays an important role as a modifier of the association between LTL and disability, CVD, and cancer. These associations have clinical implications because of the potential predictive value of LTL and deserve further investigation. PMID- 20579173 TI - The para-aortic ridge plays a key role in the formation of the renal, adrenal and gonadal vascular systems. AB - Renal, adrenal, gonadal, ureteral and inferior phrenic arteries vary in their level of origin and in their calibre, number and precise anatomical relationship to other structures. Studies of the origin and early development of these arteries have evoked sharp disputes. The ladder theory of Felix, which states that 'All the mesonephric arteries may persist; from them are formed the phrenic, suprarenal, renal and internal spermatic arteries' has been generally quoted in the anatomical textbooks without rigorous verification for 100 years. In this study, we re-examined this theory by performing micro-injection of dye and resin into rat (Rattus norvegicus) embryos. Our results revealed that most of the mesonephric arteries had degenerated before the metanephros started its ascent. The definitive renal, adrenal, gonadal, ureteral and inferior phrenic arteries appeared as new branches from the gonadal artery and/or directly from the abdominal aorta to the para-aortic ridge. Coincidental to this, the anatomical architecture of the inter-renal vascular cage, which consists of the interlobar and arcuate arteries and their collateral veins, was completed within the developing metanephros. We demonstrated that the delicate renal vascular cage switched from the primary renal artery to the definitive renal artery and that the route of venous drainage changed from the posterior cardinal vein to the inferior (caudal) vena cava. PMID- 20579172 TI - Investigating gradients of gene expression involved in early human cortical development. AB - The division of the neocortex into functional areas (the cortical map) differs little between individuals, although brain lesions in development can lead to substantial re-organization of regional identity. We are studying how the cortical map is established in the human brain as a first step towards understanding this plasticity. Previous work on rodent development has identified certain transcription factors (e.g. Pax6, Emx2) expressed in gradients across the neocortex that appear to control regional expression of cell adhesion molecules and organization of area-specific thalamocortical afferent projections. Although mechanisms may be shared, the human neocortex is composed of different and more complex local area identities. Using Affymetrix gene chips of human foetal brain tissue from 8 to 12.5 post-conceptional weeks [PCW, equivalent to Carnegie stage (CS) 23, to Foetal stage (F) 4], human material obtained from the MRC-Wellcome Trust Human Developmental Biology Resource (http://www.hdbr.org), we have identified a number of genes that exhibit gradients along the anterior-posterior axis of the neocortex. Gene probe sets that were found to be upregulated posteriorally compared to anteriorally, included EMX2, COUPTFI and FGF receptor 3, and those upregulated anteriorally included cell adhesion molecules such as cadherins and protocadherins, as well as potential motor cortex markers and frontal markers (e.g. CNTNAP2, PCDH17, ROBO1, and CTIP2). Confirmation of graded expression for a subset of these genes was carried out using real-time PCR. Furthermore, we have established a dissociation cell culture model utilizing tissue dissected from anteriorally or posteriorally derived developing human neocortex that exhibits similar gradients of expression of these genes for at least 72 h in culture. PMID- 20579174 TI - First evidence of a bipartite medial cuneiform in the hominin fossil record: a case report from the Early Pleistocene site of Dmanisi. AB - A medial cuneiform exhibiting complete bipartition was discovered at the Early Pleistocene site of Dmanisi, Georgia. The specimen is the oldest known instance of this anatomical variant in the hominin fossil record. Here we compare developmental variation of the medial cuneiform in fossil hominins, extant humans and great apes, and discuss potential implications of bipartition for hominin foot phylogeny and function. Complete bipartition is rare among modern humans (< 1%); incomplete bipartition was found in 2 of 200 examined great ape specimens and also appears in the form of a divided distal articular surface in the Stw573c Australopithecus africanus specimen. Although various developmental pathways lead to medial cuneiform bipartition, it appears that the bipartite bone does not deviate significantly from normal overall morphology. Together, these data indicate that bipartition represents a phyletically old developmental variant of the medial cuneiform, which does not, however, affect the species-specific morphology and function of this bone. PMID- 20579175 TI - Adaptation of rat jaw muscle fibers in postnatal development with a different food consistency: an immunohistochemical and electromyographic study. AB - The development of the craniofacial system occurs, among other reasons, as a response to functional needs. In particular, the deficiency of the proper masticatory stimulus affects the growth. The purpose of this study was to relate alterations of muscle activity during postnatal development to adaptational changes in the muscle fibers. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a solid (hard-diet group) or a powder (soft-diet group) diet for 63 days. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time), the total burst number and their average length exceeding specified levels of the peak activity (5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of fibers by means of immunohistochemical staining and their cross-sectional area was measured. All muscle fibers were identified as slow type I and fast type IIA, IIX or IIB (respectively, with increasing twitch contraction speed and fatigability). At lower activity levels (exceeding 5% of the peak activity), the duty time of the anterior belly of the digastric muscle was significantly higher in the soft-diet group than in the hard-diet group (P < 0.05). At higher activity levels (exceeding 20 and 50% of the peak activity), the duty time of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.05). There was no difference in the duty time of the anterior temporalis muscle at any muscle activity level. The percentage of type IIA fibers of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.01) and the opposite was true with regard to type IIB fibers (P < 0.05). The cross-sectional area of type IIX and type IIB fibers of the superficial masseter muscle was significantly smaller in the soft-diet group than in the hard-diet group (P < 0.05). There was no difference in the muscle fiber composition and the cross-sectional area of the anterior belly of the digastric and anterior temporalis muscles. In conclusion, for the jaw muscles of male rats reared on a soft diet, the slow-to-fast transition of muscle fiber was shown in only the superficial masseter muscle. Therefore, the reduction in the amount of powerful muscle contractions could be important for the slow-to-fast transition of the myosin heavy chain isoform in muscle fibers. PMID- 20579179 TI - Carry-over effects reveal reproductive costs in a long-distance migrant. AB - 1. It has been known for some time that the consequences of 'decisions' made at one point in an animal's life may not always be borne immediately. For example, numerous studies have demonstrated the trade-off between current and future breeding success across multiple taxa. 2. It is becoming increasingly clear that such processes may also operate among seasons, such that the conditions experienced at one point in the annual cycle may have significant downstream impacts, or 'carry-over effects', and this is particularly evident among migratory species. We might therefore predict that certain combinations of reproductive and migratory strategy could lead to profound carry-over effects. However, the extent to which these phenomena might generate variation in fitness within a population is unclear. 3. Here, we investigate how winter habitat selection in a long-distance migrant, with extended parental care (the Light bellied Brent goose) is influenced by parental status and how this has a counterintuitive effect on subsequent breeding success. 4. Dominant individuals and groups generally monopolize the best quality resources. In the case of geese, families are dominant; however, our findings highlight a hidden cost to raising a family. Stable isotope analysis demonstrates that later in the non-breeding season, adults with families utilize lower quality resources than non-breeders. This is probably caused by parents being constrained in habitat choice by the lower foraging efficiency of their juveniles. Consequently, parental adults end the winter in poorer condition than non-breeders. 5. We further demonstrate that parents in one year are less likely than expected to breed again in the next year and suggest that this is caused by conditions during the non-breeding period being carried over into the breeding season. In conclusion, we demonstrate previously hidden costs to raising a family, which are likely to be important in terms of life-history evolution. PMID- 20579180 TI - Evaluation of the chicory inulin efficacy on ameliorating the intestinal morphology and modulating the intestinal electrophysiological properties in broiler chickens. AB - Chicory (Cichorium intybus) belongs to plants of the Compositae family accumulating energy in the form of inulin fructan. Chicory, a prebiotic, is a fermentable oligosaccharide and oligofructose that may affect the intestinal mucosal architecture and the electrophysiological parameters. Therefore, this study was conducted to evaluate the effectiveness of adding chicory fructans in feed on the intestinal morphology and electrogenic transport of glucose in broilers. Four hundred, 1-day-old broiler chicks were randomly divided into two groups (200 birds per group) for 5 weeks. The dietary treatments were (i) control, (ii) basal diets supplemented with the dried, ground chicory pulp containing inulin (1 kg of chicory/ton of the starter and grower diets). In duodenum, dietary chicory increased the villus height and villus width and villus height to crypt depth ratio (p< 0.05), but the duodenal crypt depth remained unaffected (p > 0.05). However, in jejunum, the villus height, crypt depth and villus height to crypt depth ratio were decreased by dietary chicory compared with control birds (p < 0.05). In ileum, the villus height and villus crypt depth was decreased by dietary chicory supplementation compared with control (p< 0.05), but, the villus height to crypt depth ratio was increased (p< 0.05). Moreover, dietary chicory relatively affected the electrophysiological parameters of the intestine but did not reach significance. The amount of DeltaIsc after d-glucose addition to the jejunal mucosa was numerically higher for chicory fed birds (19 MUA/cm(2) ) than control birds (10 MUA/cm(2) ). The percentage of increase in the Isc after d-glucose addition (DeltaIsc %) was higher for chicory group upto (90%) of the control group. In colon, the actual Isc value and Isc after d-glucose addition was numerically higher for chicory fed birds than control birds (p> 0.05). Moreover, the conductance of jejunal and colonic tissues after d-glucose addition remained unaffected by the dietary chicory. In conclusion, addition of chicory to broilers diet increased the duodenal villus height, villus width and villus height to crypt depth ratio and decreased the villus height and crypt depth in both jejenum and ileum. Furthermore, dietary chicory relatively modified the small intestinal electrogenic transport of glucose in broilers. PMID- 20579177 TI - Cerebellar asymmetry in a pair of monozygotic handedness-discordant twins. AB - Increasing evidence for a cerebellar role in human cognition has accrued with respect to anatomically and functionally distinct lobules. Questions of laterality, however, have been largely overlooked. This study therefore introduced and applied a novel measurement protocol for comparatively bias-free analysis of cerebellar asymmetries. Volumetric measurements were performed on magnetic resonance images from a single pair of monozygotic handedness-discordant twins. Against a background of functional cortical asymmetry for verbal and visuo spatial functional magnetic resonance imaging activation, which was mirrored in the left-handed twin (Lux et al. 2008), between-twin differences in cerebellar asymmetry are described. Interestingly, asymmetry measures for the whole cerebellum did not correspond to either the direction of hand preference or to the weaker (functional magnetic resonance imaging) lateralization of the left handed twin. The twins both showed clockwise cerebellar torques. This mirrored a counter-clockwise cerebral torque in the right-handed twin only. Selected single cerebellar lobules V and VII displayed between-twin laterality differences that partially reflected their discrepant handedness. Whole cerebellum anatomical measures appeared to be unrelated to single functional cortical asymmetries. These analyses contribute further anatomical evidence pertaining to the existence of multiple structurally and functionally distinct cortico-cerebellar networks of the healthy human brain in vivo. PMID- 20579181 TI - Effect of rendering on protein and fat quality of animal by-products. AB - This work studies the effect of rendering on quality of meat and bone meals (MBM) processed in two Spanish rendering plants according to the standard procedure recommended by 96/499/EC Directive for MBM category III. Twelve samples of raw animal by-products and their corresponding meals were analysed for chemical composition, amino acids (AA) content, FDNB-reactive lysine content, pepsin digestibility, protein dispersibility index (PDI) and fatty acids (FA) content. There was a high variation in MBM composition between and within plants, mainly in the ash and fat content. Rendering caused a decrease in the total (p < 0.05) and the essential (p < 0.01) AA content (in crude protein basis) in both plants, because of a decrease in lysine (p < 0.001), methionine (p < 0.05), threonine (p < 0.01), leucine (p < 0.01), valine (p < 0.01) and phenylalanine (p < 0.01). Besides, there was a reduction in the cystine (p < 0.001), serine (p < 0.01) and aspartic acid (p < 0.01) content. The FDNB-reactive lysine to total lysine ratio and pepsin digestibility only decreased (p < 0.001) in the plant with more severe treatment conditions, whereas the PDI increased (p < 0.05) by the process in both plants. The saturated to unsaturated FA ratio increase on average from 0.73 to 0.88 after rendering, because of the decrease in both linoleic and linolenic acids content and the increase in palmitic and stearic acids content. The results indicate that rendering has negative effects on protein and fat quality of MBM. Variability between and within plants is attributed to differences in raw material, processing conditions and fat removing efficiency. Therefore, a continuous monitoring is recommended to assure the quality of each batch before use. PMID- 20579182 TI - Letter to the Editor regarding the review paper by Dersjant-Li and Peisker. PMID- 20579183 TI - Molecular size distribution affects portal absorption rate of casein amino acids in rats. AB - The aim of the study was to determine if differences in the molecular size of two protein sources affect in vivo intestinal absorption rates of amino acids under normal feeding conditions. Accordingly, the portal absorption rate of amino acids was studied in rats fed semi-synthetic diets containing native casein (NC) or enzymatically hydrolysed casein as the only protein sources. Enzymatic casein hydrolysate (ECH) consisted of a mixture of free amino acids (51.2% with respect to total amino acids) and low molecular weight peptides. Rats were pre-adapted to the experimental diets for 5 days prior to the absorption studies. Total free amino acid concentrations in portal vein plasma of rats fed ECH diet at 60, 105, 150 and 195 min after feeding were lower (p < 0.05) than those of rats fed NC. Lower (p < 0.05) concentrations of free threonine, proline, tyrosine, valine and tryptophan at all time points, and higher (p < 0.05) leucine at 60 and 105 min were found in rats fed ECH when compared with those fed NC in portal vein plasma. Portal flow rates of threonine, proline, tyrosine and valine were higher in NC at most time points tested, while leucine and lysine were higher for ECH fed rats 60 and 105 min after feeding. In arterial plasma, significantly (p < 0.05) higher concentrations of some individual free amino acids (proline, tyrosine, valine and tryptophan) were determined at 60, 105, 150 and 195 min after feeding, and lower leucine values after 60 and 105 min, in rats fed NC compared with those fed ECH. Results indicate that in normal feeding conditions amino acids from NC and ECH are absorbed at different rates in rats. PMID- 20579184 TI - Chromium improves production and alters metabolism of early lactation cows in summer. AB - Metabolic demands of early lactation introduce enormous challenges to dairy cows when coincided with environmental stresses. The objective of this study was to determine effects of a chromium (Cr) supplement on feed intake and blood indicators of nutrient metabolism in early lactation cows in summer. Fifteen Holstein cows at 38+/-6 days in milk were grouped based on parity and randomly assigned to three supplemental doses of 0, 0.05 and 0.10 mg Cr/kg of BW(0.75) . Cows received a basal mixed ration with a forage to concentrate ratio of 57.7:42.3, twice daily at 09:00 and 16:00 h for 9 weeks. The first 2 weeks were for adaptation, and the following 7 weeks were for weekly sampling and data collection. The Cr supplement (a Cr-methionine product with 10% Cr and 90% Met from a compound containing one atom of Cr and three molecules of Met) was mixed with 100 g of ground corn and top dressed with the morning feed. The average ambient temperature-humidity index was 77.7 units during the study. Dry matter intake increased from 21.8 to 24.2 and 23.7 kg/day when 0.05 and 0.10 mg Cr/kg BW(0.75) was provided respectively. Milk output of energy, fat, protein and total solids increased by providing Cr at 0.05 mg but not 0.10 mg/kg BW(0.75) . Both doses of Cr increased milk protein content, but the higher Cr dose reduced feed efficiency compared with control. While rectal temperature and body condition score were unaffected, cows receiving 0.05 mg and not 0.10 mg Cr/kg BW(0.75) tended to have greater respiration rate than control cows. Blood insulin and non esterified fatty acids concentrations and the insulin to glucagon ratio decreased, and serum albumin increased when cows received 0.05 mg of Cr/kg BW(0.75) . Blood glucose, glucagon, insulin-like growth factor-1, total protein, globulins, urea, BHBA, triglycerides, cholesterol, cortisol, progesterone, and high- and very low-density lipoproteins were not affected. Therefore, supplemental Cr supply at 0.05 and 0.10 mg/kg BW(0.75) improved feed intake, only at 0.05 mg/kg BW(0.75) increased milk secretion, and mainly at 0.05 mg/kg BW(0.75) altered peripheral nutrient metabolism in early lactation Holstein cows under high ambient temperatures. PMID- 20579185 TI - Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows. AB - Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFalpha), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, beta-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFalpha concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. PMID- 20579186 TI - Pantothenic acid in ruminant nutrition: a review. AB - Pantothenic acid (PA) is essential in metabolism due to its incorporation into coenzyme A and acyl-carrier-protein. In addition to fodder, ruminants have another PA source, as the micro-organisms in the rumen can synthesize PA. However, it has not been evaluated whether synthesis can meet the PA requirements of dairy cows. Furthermore, synthesis appears to be influenced by forage to concentrate ratio in the diet. It is not yet clear, if oral PA supplementations can increase the duodenal PA flow in dairy cows, but it has been reported that about 80% of supplemented PA disappears between the mouth and duodenum. However, supplementation of PA can increase blood PA levels. To give a general view of the actual state of research, the present review discusses the current knowledge, identifies gaps in knowledge and presents areas for future research. PMID- 20579187 TI - Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows. AB - A long-term study over 25 months was conducted to evaluate the effects of genetically modified corn on performance of lactating dairy cows. Thirty-six dairy cows were assigned to two feeding groups and fed with diets based on whole crop silage, kernels and whole-crop cobs from Bt-corn (Bt-MON810) or its isogenic not genetically modified counterpart (CON) as main components. The study included two consecutive lactations. There were no differences in the chemical composition and estimated net energy content of Bt-MON810 and CON corn components and diets. CON feed samples were negative for the presence of Cry1Ab protein, while in Bt MON810 feed samples the Cry1Ab protein was detected. Cows fed Bt-MON810 corn had a daily Cry1Ab protein intake of 6.0 mg in the first lactation and 6.1 mg in the second lactation of the trial. Dry matter intake (DMI) was 18.8 and 20.7 kg/cow per day in the first and the second lactation of the trial, with no treatment differences. Similarly, milk yield (23.8 and 29.0 kg/cow per day in the first and the second lactation of the trial) was not affected by dietary treatment. There were no consistent effects of feeding MON810 or its isogenic CON on milk composition or body condition. Thus, the present long-term study demonstrated the compositional and nutritional equivalence of Bt-MON810 and its isogenic CON. PMID- 20579188 TI - Putative reference genes for gene expression studies in propionate and beta hydroxybutyrate treated bovine adipose tissue explants. AB - Accurate gene expression normalization using a stable reference gene (RG) improves the reliability of quantitative real-time PCR (qPCR) results. Therefore, a validation of RGs should be done before their use. Only few studies on RGs have been done in cattle, and none in bovine adipose tissue (AT) explants, therefore, we characterize the effects of an in vitro treatment with propionate and beta hydroxybutyric acid (BHB) on the mRNA content of these RGs comparing the output data from the geNormTM and the Normfinder((c)) program. geNormTM and Normfinder((c)) estimated the most stable RGs in the following sequence for subcutaneous and for retroperitoneal AT explants treated with propionate: low density lipoprotein receptor-related protein 10 (LRP10) > hippocalcin-like 1 (HPCAL1) > glyceraldehyde-phosphate-dehydrogenase (GAPDH) > ribosomal protein S9 (RPS9) > RNA polymerase II (Pol II) > beta2 actin (ACTB) > 18S ribosomal RNA (18S rRNA). BHB treated AT explants yielded a different stability ranking for RGs using geNormTM: HPCAL1, GAPDH > Pol II > LRP10 > ACTB > RPS9 > 18S rRNA. Normfinder((c)) estimated a different stability ranking for the RGs as shown in the following sequence for subcutaneous and retroperitoneal AT explants treated with BHB: HPCAL1 > Pol II > GAPDH > ACTB > LRP10 > RPS9 > 18S rRNA. Subsequent pairwise analysis of variation of RGs using geNormTM suggested that LRP10, HPCAL1 and GAPDH should be used for accurate normalization of subcutaneous and retroperitoneal AT explants treated with propionate, while HPCAL1, GAPDH and Pol II should be used for BHB treatment. PMID- 20579189 TI - In vitro rumen fermentation of the tropical grass Pennisetum purpureum and mixtures with browse legumes: effects of tannin contents. AB - The fermentation of Pennisetum purpureum, alone (PP) or substituted with 0.30 of the tanniferous legumes Acacia cornigera (AC), Albizia lebbekoides (AL), Leucaena leucocephala (LL) and the saponin-rich Enterolobium cyclocarpum (EC) was studied in vitro, in presence or absence of polyethylene glycol (PEG) as tannin binder. Inactivation of tannins with PEG increased (p < 0.05) gas production with AL and LL from 8 and 12 h to the end of the incubation period respectively. When PEG was added, LL and AC promoted a higher (p < 0.05) gas volume than PP in the first 12 h incubation, and there were not differences between PP and AL. Substrate mixtures reduced (p < 0.05) methane volume produced compared with PP, but this was not related to PEG inclusion (p > 0.10). There was a trend (p = 0.06) for a higher 48 h bacterial attachment to the substrate when incubated without PEG. The decrease in fermentation of EC from 12 h incubation onwards could be associated with a negative mid-term effect of saponins over cellulolytic bacterial activity. It is concluded that the effects of tannins on microbial fermentation of mixed forage substrates are variable, depending on their nature, but do not have a marked impact on bacterial adhesion or methane production. PMID- 20579190 TI - Impact of inulin and a multispecies probiotic formulation on performance, microbial ecology and concomitant fermentation patterns in newly weaned piglets. AB - The effect of inulin and a multispecies probiotic formulation on performance and microbial parameters in a 28 days feeding trial with newly weaned piglets was assessed. Forty-eight piglets were allocated to a 2 * 2 factorial experiment involving two levels of inulin supplementation (0% or 0.4%) and two levels of probiotics (0 or 1 * 10(9) CFU/kg as fed, comprising enterococci, lactobacilli and bifidobacteria). In digesta samples obtained at slaughter (stomach, jejunum, ileum and colon), selected bacterial groups were enumerated and lactic acid, short chain fatty acids and ammonia concentrations analysed. The overall performance of piglets was unaffected by treatment. Inulin increased total aerobes in stomach and jejunum (p < 0.05), whereas enterococci declined in colon of the inulin group (p < 0.05). Furthermore decreasing colonic acetic acid (p < 0.01) and increasing lactic acid (p < 0.05) was observed for inulin. Probiotics increased total aerobes (p < 0.05) and enterococci (p < 0.01) in ileum and lactobacilli (p < 0.05), enterococci and gram-negative anaerobes (p < 0.01) in colon. Moreover, dry matter content in stomach and colon was lower and acetic acid in colon increased (p < 0.05). A decrease in ileal pH value was noted symbiotically for both additives. However, several parameters showed no synbiotic, but distinct individual effects of inulin and probiotics. Effects occurred along the entire gastrointestinal tract without restriction to the colon. PMID- 20579191 TI - Stress and stress-related factors of patients after renal transplantation in Taiwan: a cross-sectional study. AB - AIMS: The aim of this study is to quantify the amount and causes of stress in renal transplant recipients. BACKGROUND: After renal transplantation, patients may encounter physical and psychosocial problems. Through patient collaboration with healthcare professionals, treatment after transplantation is aimed at restoring and maintaining a 'normal' life. To achieve quality of life, research needs to quantify the amount and causes of stress of renal transplant recipients, from a patient-centred perspective. DESIGN: A cross-sectional, descriptive study. METHODS: The study was conducted in the outpatient department of a medical centre in northern Taiwan from September 2005-February 2006. The recipients were a convenience sample of 153 participants who had undergone renal transplantation. RESULTS: The results showed that renal transplant recipients had low to moderate stress in four areas. Gender (male), self-efficacy and hospitalisation for infection explained 17% of the variance found for the stress of uncertainty; hospitalisation for rejection and infection explained 22% of the variance for complications; and gender (male) and self-efficacy explained 8% of the variance for the interactions with others. Post-transplant time was not found to be a predictor of stress. CONCLUSION: After renal transplantation, patients experience multi-dimensional stresses that previous research has not explored. Self-efficacy was shown to be a significant predictor of the stress of uncertainty and interactions with others. Enhancing recipients' self-efficacy of self-care behaviour can lower the stress that found in three areas. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should develop an evidence-based programme for stress management for renal transplantation patients that incorporates strategies to enhance patient's self-efficacy of self-care behaviour. Recipients' beliefs in their ability to successfully perform self-care behaviour can be promoted by a mastery experience, vicarious experience with other patients, social persuasion and re-explanation of somatic and emotional states by discussing coping methods with healthcare professionals. PMID- 20579192 TI - Critical care nurses' experiences of follow-up visits to an ICU. AB - AIM: The aim of this study was to describe critical care nurses' experiences of follow-up visits for formerly critically ill people discharged from an intensive care unit and their close relatives. BACKGROUND: The critical illness experience affects the ill person and their close relatives not only during the stay in an intensive care unit, but also for a long time afterwards. Follow-up visits were introduced to offer people the opportunity to talk about their experiences. This activity has not been studied earlier from the perspective of critical care nurses. DESIGN: The design of this study was qualitative. METHOD: Eight critical care nurses narrated their experiences of follow-up visits by formerly critically ill people and their close relatives to an intensive care unit. Data were collected during 2007-2008. Qualitative thematic content analysis was applied to the interview texts. RESULTS: The findings show that to feel they were doing a good job it was vital for the critical care nurses to be well prepared for the follow-up visits. It was difficult, in a positive way, to recognise formerly critically ill people when they returned looking healthy. The critical care nurses were disappointed that their former patients remembered so few real events. The follow-up visits gave the critical care nurses a new picture of how the critically illness experience influenced the former patient's everyday life during and after their stay in the intensive care unit and how it affected the lives of their close relatives. CONCLUSIONS: Through sharing the experiences of formerly critically ill peoples' and their close relatives' critical care nurses receive valuable feedback about their work. RELEVANCE TO CLINICAL PRACTICE: Receiving feedback about one's work from follow-up visits gives critical care nurses the possibility for to evaluate given care. Follow-up visits to intensive care units can provide them with valuable knowledge that might lead to improved nursing care. PMID- 20579193 TI - Editorial: Are we ready? Preparing nurses to respond to disasters and emerging infectious diseases. PMID- 20579194 TI - Pressure ulcer guideline development and dissemination in Europe. AB - AIMS AND OBJECTIVES: To explore the current state of pressure ulcer guideline development and dissemination, from national to local level (i.e. nursing homes) in six European countries: England, Germany, Italy, the Netherlands, Portugal and Sweden. BACKGROUND: Pressure ulcers are a persistent problem in healthcare institutions. Their prevalence is influenced by many factors, one of them being the development and dissemination of pressure ulcer guidelines. These are difficult and complex processes and it is not clear whether they differ between European countries. DESIGN: Literature review and semi-structured interviews. METHOD: Interviews were conducted in six countries at national and nursing home level. RESULTS: Four countries had national pressure ulcer prevention and treatment guidelines. Portugal had no national guidelines and Sweden had shifted the responsibility to regional level. All participating nursing homes had pressure ulcer guidelines except those in Portugal. Control and monitoring of guideline dissemination was carried out only in Sweden and England. CONCLUSIONS: All countries studied have national or regional pressure ulcer prevention and treatment guidelines, except Portugal. Portugal is also the only country where none of the nursing homes included had pressure ulcer guidelines. Because the dissemination of such guidelines does not imply actual implementation, further research should focus on the implementation process. RELEVANCE TO CLINICAL PRACTICE: Clinical guidelines, like pressure ulcer guidelines, are important tools in guiding the care processes in healthcare institutions. Successful dissemination of guidelines from national level to individual healthcare institutions is a first and necessary step in actually applying them. Monitoring of the guideline dissemination process is therefore essential. PMID- 20579195 TI - Increasing pressure ulcer rates and changes in delivery of care: a retrospective analysis at a University Clinic. AB - AIM: To evaluate the relation between pressure ulcers and delivery of care. BACKGROUND: No decrease of pressure ulcer rates could be recognised in acute hospital care, despite intensive efforts in prevention. Furthermore, reports show increasing rates. DESIGN: Retrospective analysis of hospital data. METHODS: The study included all inpatients from year 1 (2003/2004) and 4 (2006/2007) of the interdisciplinary decubitus project. Information on ulcers was recorded at admission, discharge and in case of new events. We analysed the effect of age, length of stay, operation and intensive care episode. In logistic regression, we used the existence of ulcers and the appearance of new ulcers as dependent variables. RESULTS: Parallel to a decrease in the number of inpatients, age, length of stay and operation frequency rose between 2003 and 2007. Higher age, longer length of stay, operation, intensive care episode and year 4 raise the odds for ulcers in univariate and with exception of operation in multivariate analyses. With exception of operation and year 4, the same variables raise the odds for new ulcers, too. CONCLUSIONS: The increase of pressure ulcer frequency could be related to changes in delivery of care. The adverse event pressure ulcer will become more important in hospital care. RELEVANCE TO CLINICAL PRACTICE: There is no decrease in pressure ulcer rates, albeit enormous efforts in prevention. Hospital care has been facing changes in case mix. Age, length of stay and intensive care episodes are related to increasing ulcer rates at a University Clinic. Nursing management has to be aware of additional workload for pressure ulcer management in the future. PMID- 20579196 TI - Diagnostic accuracy of two pressure ulcer risk scales and a generic nursing assessment tool. A psychometric comparison. AB - AIM: Comparison of the diagnostic accuracy of two pressure ulcer risk assessment scales and one generic nursing assessment tool. BACKGROUND: Guidelines for pressure ulcer prevention recommend an initial risk screening of all patients, followed by appropriate nursing interventions. Additionally, personal and financial resources have to be allocated carefully to avoid excessive or too little treatment. Risk assessments should be accurate and applicable, and some studies showed that generic nursing tools also provide specific information for nursing diagnoses, like risk for pressure ulcer. DESIGN: Cross sectional observational study. METHODS: A total of 1053 adult patients of a university hospital in Germany were investigated. For each patient, the Braden Scale, the Waterlow Scale and the Care Dependency Scale were completed. A skin inspection was conducted by trained nurses. Correlations between the three scales and the mean values of each pressure ulcer risk assessment scales for each Care Dependency Scale value were calculated. To determine the association between susceptibility to pressure ulcer and observed pressure ulcer, the area under the curve was calculated. RESULTS: There was a higher correlation between the Braden Scale and the Care Dependency Scale (r = 0.82) than between the two pressure ulcer risk assessment scales (-0.65). The highest area under the curve was reached by the Braden Scale (0.86), followed by the Care Dependency Scale (0.83) and the Waterlow Scale (0.81). Only the Braden Scale (cut-off 18) and the Care Dependency Scale (cut-off 65) reached the psychometric requirements of at least 70% sensitivity and 70% specificity. CONCLUSIONS: The Care Dependency Scale could be used for both a general nursing assessment and as a screening tool for risk for pressure ulcers. The Braden Scale showed the highest association with the occurrence of pressure ulcer. RELEVANCE TO CLINICAL PRACTICE: The Care Dependency Scale is a useful screening tool to identify patients at risk for pressure ulcers. Nursing assessment activities might be reduced by using a generic nursing assessment tool also for specific risk screening. PMID- 20579197 TI - Effectiveness of the auscultatory and pH methods in predicting feeding tube placement. AB - AIMS AND OBJECTIVES: This study was designed to determine the effectiveness of the auscultatory and pH methods in predicting feeding tube location in critically ill patients. BACKGROUND: There is confusion about how nurses should asses feeding tubes location at the bedside. The most common method for determining tube location is the auscultatory method. It is known that auscultation is an unreliable method and additional data relating to bedside methods are needed to assist nurses in making a decision regarding tube location. DESIGN: A methodological study. METHODS: The sample consisted of 44 new insertions of feeding tubes. Data from a total of 44 auscultations relating to tube position and gastrointestinal aspirates for pH were obtained from 32 critically ill adult patients ranging in age from 38-87 years. Results from the auscultatory and pH tests were compared with the location of the tube as determined by radiography. A total of 44 feeding tube applications were investigated using the auscultatory and pH methods and concurrently with X-rays to determine the feeding tube position. Nurses used the auscultatory method to predict tube position, a concurrent researcher aspirated fluid from the feeding tube, and samples were tested for pH within five minutes of radiographs taken to determine tube location. pH was measured with a test strip. RESULTS: Mean pH level in the gastrointestinal aspirates was 4.23 (SD 1.20). Approximately 89% of the pH strip readings from gastrointestinal fluid were between 0-5. A pH of <5 successfully identified 90.4% of the 44 feeding tube cases. CONCLUSION: The pH method is effective in determining the feeding tube position, but the auscultatory method is not effective in determining the feeding tube position. RELEVANCE TO CLINICAL PRACTICE: Simple bedside assessment of gastrointestinal aspirate pH is useful for predicting feeding tube position. PMID- 20579198 TI - Preparation of parenteral medicines in clinical areas: how can the risks be managed - a UK perspective? AB - AIMS AND OBJECTIVES: This article provides an overview of preparation of parenteral medicines in clinical areas. It describes the development of a tool to allow preparation of these medicines to be scored for risk. The article shows how this work was adopted by the National Patient Safety Agency (NPSA) and was subsequently issued as Patient Safety Alert 20 (Injectable Medicines). BACKGROUND: Although there are well-established standards for preparation of parenteral medicines in pharmacy, there were no equivalent standards for their preparation in clinical areas, where risks to patients from medication error and microbiological contamination are greater. Use of a risk assessment process allows highest risk items to be targeted for transfer to pharmacy preparation. Defined standards and competency-based training should reduce risk for preparation of those items remaining in clinical areas. METHOD: Discursive. CONCLUSIONS: This article identifies the risks involved in the preparation of parenteral medicines in clinical areas and describes ways in which these risks can be minimised. RELEVANCE TO CLINICAL PRACTICE: Use of risk assessment allows targeted transfer of high-risk parenteral medicines to pharmacy preparation, where risks of medication error and microbiological contamination are lower. This transfer liberates nursing time for patient benefit. PMID- 20579199 TI - Predictors of fatigue in patients with heart failure. AB - AIMS AND OBJECTIVES: The purpose of this study was to examine the level of fatigue perceived by patients with heart failure and to explore the potential factors influencing fatigue. DESIGN: A cross-sectional, correlational design was used. METHODS: A convenience sample of 105 patients was recruited between July and September 2003 in northern Taiwan. The patients were interviewed, and their perceived fatigue was assessed with the modified Piper Fatigue Scale. The factors influencing fatigue were determined using a stepwise linear regression model. RESULTS: The majority of patients with heart failure experienced mild-to-moderate fatigue. Patients with higher levels of fatigue had worse physical functioning and more severe symptomatic and psychological distress. Symptomatic distress, psychological distress (depression and anxiety), New York Heart Association class, activities of daily living (ADL) and appraisal support by health care providers could explain 57.4% of the total variance of fatigue. Symptomatic distress was the strongest predictor of fatigue. CONCLUSION: Higher levels of fatigue were found in patients with heart failure who had symptomatic or psychological distress. Additional research focusing on developing effective methods to reduce fatigue in patients with heart failure is recommended. RELEVANCE TO CLINICAL PRACTICE: Nurses should help patients with heart failure to monitor their symptoms and report them to health care providers. Early management of symptoms and support by health care providers may reduce patients' fatigue, help maintain their physical functioning and improve their quality of life. PMID- 20579200 TI - Hand dermatitis among paediatric nurses. AB - AIMS AND OBJECTIVES: Hand dermatitis is regarded as one of the most often observed dermatological disorders among nurses. This study was carried out to investigate the incidence of self-reported hand dermatitis and related factors among paediatric nurses. BACKGROUND: The most common occupational skin disease in the nursing profession is hand dermatitis. Various risk factors are known to exist including the type of soap used at work, the number of hand washes per shift and the nursing job category, among others. DESIGN: This study was conducted among a group of 158 nurses based in three paediatric hospital departments in Bursa. METHODS: Data were collected using a questionnaire prepared by the investigators. Each nursing unit was visited twice by a single investigator. All nurses working at the time of each visit were questioned and examined. RESULTS: Of the nurses, 47.5% had hand dermatitis. The damage was not correlated with age or the type of soap used at work, but was significantly correlated with the hospital, unit, number of hand washes (p < 0.05), history of allergy (p < 0.01) and type of hand protection (p < 0.001). Hand dermatitis was more common in the ICU and infectious disease units. Most of the nurses did not apply hand cream at the hospital. CONCLUSIONS: Damage to hands is a common and potentially serious problem among nurses and is associated with unit, glove usage and hand-washing practices instead of with demographic factors. A high frequency of hand dermatitis was observed among paediatric nurses. RELEVANCE TO CLINICAL PRACTICE: The proper preventive programmes should be implemented for those nursing staff working in high-risk units. PMID- 20579201 TI - Breastfeeding and obesity at 21 years: a cohort study. AB - AIMS: To determine the influence of breastfeeding on overweight and obesity, as determined by body mass index in early adulthood. BACKGROUND: Obesity is a contemporary epidemic and linked to increased risk of later cardiovascular disease and type 2 diabetes. The success of long-term treatment is modest. Protective factors, such as potentially, and breastfeeding, are few and very important. There are uncertainties as to whether breastfeeding has a protective effect, especially in adults, or whether it is a reflection of other markers of obesity that are more linked to cardiovascular disease and diabetes risk. Some studies suggest that breastfeeding is protective in later life for cardiovascular disease and atherosclerosis. DESIGN: Epidemiological analysis of longitudinal data set. METHODS: We collected data about breastfeeding duration, body mass index of children at 21 years and confounding variables from an ongoing longitudinal study of a singleton birth cohort of 7223 children in Brisbane. We assessed the duration of breastfeeding at six months and prevalence of overweight and obesity at 21 years by body mass index. Adjustment for potential confounders was by multivariable multinomial logistic regression. RESULTS: Data were available for 2553 young adults. In neither the unadjusted or adjusted analysis was longer duration of breastfeeding associated with reduction in obesity at 21 years. CONCLUSIONS: Findings of this investigation are consistent with breastfeeding not independently affecting body mass index in young adults. RELEVANCE TO CLINICAL PRACTICE: Breastfeeding has a range of important benefits for infants, mothers and families, although duration of breastfeeding may not play a substantial role in preventing adult onset obesity. PMID- 20579202 TI - Triage, treat and transfer: reconceptualising a rural practice model. AB - AIM: This article argues that the current model of emergency practice in rural Victorian hospitals, which relies heavily on visiting medical officers, needs to be reconceptualised if emergency services are to be supplied to rural communities. BACKGROUND: Medical workforce shortages are manifesting in Victoria as a reduction in emergency care services from rural hospitals. The suggested alternative model of emergency care involves advancing nursing practice to enable a redistribution of clinical capacity across the health care team. Clinicians will need to work collaboratively and continuously negotiate their roles to meet the patient's and the clinical team's needs. DESIGN: Systematic review. METHODS: This article is based on a review of the Victorian and Australian literature on the subject of Victorian health services and policy, emergency care, collaboration, communication and rural nurse scope of practice and roles. Emergency care activity was drawn from data held in the Victorian Emergency Management Dataset and personal communications between one of the authors and hospital executives in a small selection of rural hospitals in Victoria. RESULTS: The evidence reviewed suggests that the current emergency practice profile of rural hospitals in Victoria does not reflect the reconceptualised model of rural emergency practice. Instead, only a small proportion of non-urgent presentations is managed by nurses without medical support, and the data suggest that metropolitan nurses are more likely to manage without medical support than rural nurses. CONCLUSION: Reconceptualising rural emergency care in Victoria will require significantly greater investment in rural nurses' knowledge and skills to enable them to operate confidently at a more advanced level. Clinical teams that deliver emergency service in rural hospitals will be expected increasingly to work collaboratively and interprofessionally. RELEVANCE TO CLINICAL PRACTICE: This article offers some directions for advancing nursing practice and strategies for improving interprofessional collaboration in the delivery of rural emergency care. PMID- 20579203 TI - Organisational climate, organisational commitment and intention to leave amongst hospital nurses in Taiwan. AB - AIMS AND OBJECTIVES: To examine: (1) Taiwanese nurses' perceptions of organisational climate, levels of organisational commitment and intention to leave, as well as relationships between these three variables; (2) demographic differences in the levels of these variables; and (3) mediating effects of organisational commitment on the relationship between organisational climate and intention to leave. BACKGROUND: Organisational climate is related to organisational commitment and affects nurses' performances and attitudes towards an organisation. DESIGN: A cross-sectional, descriptive design. METHOD: Registered nurses working in eight hospitals in southern Taiwan for more than six months were recruited. Data were collected using the Litwin and Stringer's Organisational Climate Questionnaire, Organizational Commitment Questionnaire and a five-item scale measuring intention to leave. Questionnaires were distributed to 612 potential participants; 486 valid returned questionnaires were analysed. RESULTS: The study's participants were generally satisfied with their hospital's climate and yet claimed low commitment to their organisation and, nevertheless, reported low intention to leave their job. Single nurses were more satisfied with their hospital's climate and were more committed to their hospital and had a lower intention to leave their job compared to married nurses. Nurses working in district hospitals perceived a better hospital climate and had a lower intention to leave than nurses working in teaching or regional hospitals. Staff nurses perceived a better organisational climate than did nurse managers. Organisational climate, organisational commitment and intention to leave were intercorrelated. Organisational climate had almost 60% indirect effect on organisational commitment related to intention to leave. CONCLUSIONS: Creating a good organisational climate may increase nurses' organisational commitment and, in turn, decrease their intention to leave. RELEVANCE TO CLINICAL PRACTICE: To motivate nurses' positive organisational behaviours and to address their diverse needs, hospital administrators are encouraged to understand nurses' work-climate perceptions and to address nurses' varied demographic factors. PMID- 20579204 TI - Impacts of unit-level nurse practice environment and burnout on nurse-reported outcomes: a multilevel modelling approach. AB - AIM: To investigate impacts of practice environment factors and burnout at the nursing unit level on job outcomes and nurse-assessed quality of care in acute hospital nurses. BACKGROUND: Prior research has consistently demonstrated correlations between nurse practice environments and nurses' job satisfaction and health at work, but somewhat less evidence connects practice environments with patient outcomes. The relationship has also been more extensively documented using hospital-wide measures of environments as opposed to measures at the nursing unit level. DESIGN: Survey. METHOD: Data from a sample of 546 staff nurses from 42 units in four Belgian hospitals were analysed using a two-level (nursing unit and nurse) random intercept model. Linear and generalised linear mixed effects models were fitted including nurse practice environment dimensions measured with the Revised Nursing Work Index and burnout dimensions of the Maslach Burnout Inventory as independent variables and job outcome and nurse assessed quality of care variables as dependent variables. RESULTS: Significant unit-level associations were found between nurse practice environment and burnout dimensions and job satisfaction, turnover intentions and nurse-reported quality of care. Emotional exhaustion is a predictor of job satisfaction, nurse turnover intentions and assessed quality of care as well besides various nurse work practice environment dimensions. Nurses 'ratings of unit-level management and hospital-level management and organisational support had effects in opposite directions on assessments of quality of care at the unit; this suggests that nurses' perceptions of conditions on their nursing units relative to their perceptions of their institutions at large are potentially influential in their overall job experience. CONCLUSION: Nursing unit variation of the nurse practice environment and feelings of burnout predicts job outcome and nurse-reported quality of care variables. RELEVANCE TO CLINICAL PRACTICE: The team and environmental contexts of nursing practice play critical roles in the recruitment and retention of nurses, and as well as in the quality of care delivered. Widespread burnout as a nursing unit characteristic, reflecting a response to chronic organisational stressors, merits special attention from staff nurses, physicians, managers and leaders. PMID- 20579205 TI - A clinical trial of an individualised intervention programme for family caregivers of older stroke victims in Taiwan. AB - AIM AND OBJECTIVE: To explore the long-term effects of a discharge-preparation programme targeting Taiwanese family caregivers of older patients with stroke. BACKGROUND: Little is known about the effects of interventions for caregivers of patients with stroke in Asian and Chinese families. DESIGN: A randomised experimental design was used. METHOD: Participants included 158 older patients with stroke (72 in the experimental group and 86 in the control group) and their family caregivers. A caregiver-oriented intervention programme was designed to increase caregiver preparedness, to enhance caregiver perception of balance between competing needs and to satisfy specific needs during the transition between hospitalisation and discharge. Long-term outcomes were measured by caregiver's health-related quality of life, quality of care, stroke patient's self-care ability, patient's health-related quality of life and service utilisation. Longitudinal data were analysed by the generalised estimating equation approach. RESULTS: During the 12 months following discharge of older patients with stroke, caregivers in the experimental group provided significantly better quality of care (beta = 0.45; p = 0.03) than the control group. Between the sixth-twelfth months following discharge, patients in the control group were more likely to be institutionalised than those in the experimental group (chi(2) = 5.11; p = 0.03). CONCLUSION: Using a sample from Taiwan, this intervention programme succeeded in improving quality of care provided by family caregivers to older patients with stroke and in decreasing the likelihood of their institutionalisation. RELEVANCE TO CLINICAL PRACTICE: Older Chinese patients with stroke and their family caregivers can benefit from an individualised programme that prepares caregivers for patient discharge. Similar programmes may be applicable to other countries with Chinese populations. PMID- 20579206 TI - Life stories and biography: a means of connecting family and staff to people with dementia. AB - AIMS: This article assesses the Family Biography Workshop (FBW) designed to support family and staff to co-construct the history of the person with dementia in residential care. BACKGROUND: Family-staff conflict in residential dementia care is a major stressor that disturbs effective relationships and contributes to stress. Biographical research has been found to improve communication and promote family-staff relations. Few studies focus on family biography as an approach that promotes positive relations that translate into inclusive care interactions. DESIGN: A qualitative descriptive approach was used to assess the influence of participation in the FBW and the impact of developing biographical knowledge on family-staff caregiver attitudes, perceptions of roles, conflict and the subsequent management of stress using participatory care practices. METHODS: The FBW process involved seven family caregivers, seven staff and one researcher working collaboratively through a series of six weekly two-hour sessions, designed to help them build a biography of the person with dementia. RESULTS: For family caregivers, reviving memories of their relatives as 'whole' persons enabled some to 'stand outside' and see beyond the disease-saturated context. For staff, 'opening possibilities' of 'seeing' the resident within the family context empowered them to engage in genuine participatory practices. Residents benefited from being connected as staffs''know how' in initiating and engaging developed. CONCLUSION: Future research will examine the effects of the FBW on the dynamics of family-staff roles and relationships. This research aims to reduce stress from role inadequacy, task burden, poor relationships and improve staff attitudes towards family participation. RELEVANCE TO CLINICAL PRACTICE: This study substantiated the FBW by revealing understanding of the meaning of biography work for family and relatives in care; providing effective support that empowered staff to confidently relate; and fostering engagement in inclusive care practices that encouraged residents' initiatives. PMID- 20579207 TI - Effectiveness of applying empowerment strategies when establishing a support group for parents of preterm infants. AB - AIMS: The objectives of this study were to apply empowerment strategies to the establishing of a support group for parents of preterm infants who were recently discharged home and to examine its effectiveness in terms of self-efficacy, perceived stress and depression among the parents. BACKGROUND: While the concept of empowerment has been applied when establishing various patient support groups, it has not been explicitly used for parents of preterm infants. DESIGN: This study applied a quasi-experimental design. METHOD: The inclusion criteria were parents of infants with a birth gestational age of <37 weeks who were expected to be discharged home within one week. A total of 70 parents of preterm infants participated in this study, made up of 35 participants each in the intervention and in the control groups. The intervention group received three months of support applying empowerment strategies, while the control group received usual care only. RESULTS: The results, relative to the control group at post-test, demonstrated that the intervention group showed significantly higher scores for self-efficacy when using resources as well as significantly decreased scores for depression. For parents of preterm infants with a very low birth weight, the intervention group showed a significant decrease in perceived stress relative to controls, but this was not seen in parents of preterm infants without very low birth weight. There was no significant difference in the scores for self-efficacy when performing parental roles. CONCLUSIONS: his study demonstrated the effectiveness of support groups for parents of preterm infants that apply empowerment strategies, which decreased parental depressive symptomatology and increased parental self-efficacy when utilising resources. The intervention also effectively decreased the perceived stress level in parents of infants with very low birth weight. RELEVANCE TO CLINICAL PRACTICE: Health professionals should apply empowerment strategies when establishing parental support groups for preterm infants. PMID- 20579208 TI - Anxiety levels of mothers whose infants have been cared for in unit level-I of a neonatal intensive care unit in Turkey. AB - AIM: In most cases, admission of an infant to the intensive care unit is unexpected and is stressful for their mothers. The aim of this study is to examine factors affecting anxiety level of mothers whose infant is admitted to the neonatal intensive care unit. BACKGROUND: Anxiety disorders figure among the most frequent psychiatric disorders in the population, and anxiety symptoms are among the most common. DESIGN: A descriptive correlational design. SETTING: Neonatal intensive care unit of Women's Health and Diseases, Education and Research Hospital in Turkey. PARTICIPANTS: A total of 151 women who had an infant in NICU. METHODS: A questionnaire form was used and included two instruments. The first measured characteristics of mothers and infants, and the second was the 'State-Trait Anxiety Inventory'. RESULTS: Of the mothers, 33.8% were between the ages 25-29, 41.7% of the subjects had a primary education, 89.4% were housewives, 64.9% had social security and 58.9% of subjects had low family incomes. Of the 151 subjects, 75.5% had planned their pregnancy, and 41.7% were primiparas. It was determined that maternal age, education, income; planned pregnancy, having complications of pregnancy, receiving antenatal care, type of labour, gestational age of the infant at birth, reasons for hospitalisation of the infant and birth weight did not affect maternal anxiety levels. Maternal anxiety was significantly (p < 0.05) related to the infants' gender and duration of hospitalisation, with statistically significant differences. RELEVANCE TO CLINICAL PRACTICE: Anxiety in mothers was significantly higher if their infant was a boy. This finding can be a result of mother's cultural and religious values. A better understanding of the psychosocial aspects such as cultural values and norms affecting maternal and child health of the perinatal period will contribute to improved health care and better outcomes. Nurses will be better prepared to assist mothers of babies in the NICU to cope with the experience through exploration of these aspects of the mother, infant and experience. PMID- 20579209 TI - Womens' opinions on intrapartal care: development of a theory-based questionnaire. AB - AIM: To develop a patient questionnaire specific to intrapartal care, based on the theoretical foundation of the general instrument Quality from the Patient's Perspective (QPP). BACKGROUND: Existing general patient questionnaires do not take intrapartal care aspects fully into account, and available intrapartal specific patient questionnaires tend to have a weak theoretical foundation. DESIGN: A cross-sectional, nationwide study carried out during a two-week period in 2007 at Swedish maternity units. METHOD: An intrapartal-specific QPP questionnaire (QPP-I) was developed by combining a selection of 22 items from the short and long versions of the QPP with 10 newly constructed items. Responses were obtained from 739 women (63% response rate). The dimensionality of the QPP-I was assessed using structural equation modelling (a nested factor model). Non parametric statistics were used for subgroup comparisons. RESULTS: A nested model with a general factor including all 32 items and 10 subordinate factors was developed. Most scales had acceptable reliability coefficients (0.73-0.93), and a meaningful pattern of subgroup differences was obtained. CONCLUSIONS: The QPP-I is theory based and has its roots in a patient perspective. It was developed using a nationwide sample of Swedish women receiving intrapartal care, and an advanced statistical method was used. The outcome of this initial empirical trial was promising but needs to be tested in different countries and cultures. RELEVANCE TO CLINICAL PRACTICE: By combining womens' responses on perceived reality and subjective importance ascribed to the various aspects of care measured, the QPP-I offers the care provider better guidelines on which elements to focus quality improvement work on, than would be the case if only a rank order of perceived reality ratings was available. PMID- 20579210 TI - Commentary on Young, A (2008) The legal duty of care for nurses and health professional. Journal of Clinical Nursing, 18, 3071-3078. doi 10.1111/j.1365 2702.2009.02855.x. PMID- 20579212 TI - All Bowen's disease is squamous cell carcinoma in situ, but all squamous cell carcinoma in situ is not Bowen's disease. PMID- 20579213 TI - CD8-positive granulomatous mycosis fungoides: a case report with review of the literature. AB - Granulomatous mycosis fungoides (GMF) represents an uncommon variant of mycosis fungoides (MF) characterized by the presence of an associated granulomatous reaction. Most cases of GMF are CD4 positive, and CD8 positive cases are extremely rare. Herein, we report a case of CD8-positive GMF. A 75-year-old Japanese woman presented with brownish maculae on the trunk and upper and lower extremities. She had been diagnosed with MF, and most of the eruption improved by psoralen ultraviolet A therapy. However, the eruption relapsed and gradually expanded 5 months prior to her visit to our hospital. Histopathology showed an atypical lymphocytic infiltrate in the dermis accompanied by granulomatous reaction with multinucleated giant cells. Epidermotropism was evident and elastophagocytosis was also found. Immunohistochemically, the atypical lymphocytes expressed betaF1, CD3 and CD8, and some of the atypical lymphocytes were also T cell intracellular antigen-1 positive. These findings were consistent with CD8-positive GMF. The dermatopathological diagnosis of GMF is challenging in some cases because of the prominent secondary granulomatous reaction. Therefore, when dermatopathologists diagnose granulomatous skin lesions, GMF should also be considered. In addition, the prognosis of GMF, especially CD8-positive GMF, is still controversial. Additional studies are required to clarify the clinicopathological features of CD8-positive GMF. PMID- 20579214 TI - Elastofibromatous change of the oral mucosa: case report and literature review. AB - Elastofibroma is an uncommon fibrous pseudotumor that usually occurs in the subscapular region of middle-aged and older adults. Since its seminal description, cases of elastofibroma or elastofibroma-like proliferations have been identified at several anatomic locations, including the foot, hand, thigh, olecranon, gastrointestinal tract, trachea, dorsal spine and eye. Involvement of the oral cavity is rare, with only four cases reported to date. Herein, we report a case of elastofibromatous change in the soft palate of a 55-year-old man and review the literature regarding pathogenesis, clinicopathologic features, differential diagnosis and management. PMID- 20579215 TI - Pharmacotherapy of cholestatic liver diseases. AB - New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases. PMID- 20579216 TI - Th17 cells: the emerging reciprocal partner of regulatory T cells in the liver. AB - T helper cells that produce interleukin-17 (IL-17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid-related orphan nuclear receptor-gammat. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)-beta induces Treg-specific transcription factor Forkhead box P3(FOXP3), while the addition of IL-6 to TGF-beta inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL-6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL-2 and IL-27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune-related liver diseases. PMID- 20579217 TI - Inflammatory bowel disease in the Asia-Pacific area: a comparison with developed countries and regional differences. AB - The Asia-Pacific region has been marked as an area with a low incidence of inflammatory bowel disease (IBD), although confusion always existed as to whether this low incidence was a result of low diagnostic awareness, a high incidence of infective diarrhoea and its diagnostic overlap or a true low incidence. As epidemiological studies from this region are being made available it is clear that the incidence and prevalence rates of IBD in Asia-Pacific region are low compared with Europe and North America. They are however, increasing rapidly. There are substantial variations in the incidence and prevalence rates of IBD in various ethnic groups in Asia. The highest incidence rates are recorded from India, Japan and the Middle East and there exists a genetic predisposition of South Asians (Indians, Pakistanis and Bangladeshis) to ulcerative colitis (UC). It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South-East Asia have higher rates than Chinese and Malays. While there is a host genetic predisposition, environmental factor(s) may be responsible for this difference. The clinical phenotypes and complication rates of Asian IBD resemble those of the Caucasian population in general, but some heterogeneity is observed in different regions of Asia. There is no evidence of a north-south or an east-west divide in the Asia-Pacific region. The available studies suggest an increasing incidence of UC in the Asia-Pacific region and hence it is an appropriate time to launch well-designed epidemiological studies so that etiopathogenetic factors can be identified. There is a male predominance in Crohn's disease in the Asian population. The NOD2/CARD15 gene is not associated with CD in the Japanese, Korean, Chinese and Indian population. PMID- 20579218 TI - Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: a meta-analysis. AB - OBJECTIVE: To systematically evaluate whether immunochemical fecal occult blood tests (iFOBT) could improve clinical performance and test accuracy in screening and surveillance for advanced colorectal neoplasms. METHODS: Eligible articles were identified by searches of electronic databases. All randomized trials and diagnostic cohort trials directly comparing iFOBT with guaiac-based FOBT (gFOBT) were included. A statistical analysis was performed using RevMan 4.2.8. A sensitivity, specificity and summary receiver operating characteristic curve was performed using Meta Disc. RESULTS: We identified five randomized trials and 11 diagnostic cohort trials. In the randomized trials, the detection rates of advanced colorectal neoplasms with iFOBT or gFOBT were 2.23 percent and 1.24 percent, respectively. The pooled odds ratio (OR) was 1.50 (95% CI 0.94-2.39). In cohort trials, the advanced neoplasm detection rates of iFOBT or gFOBT were 1.44 percent and 0.50 percent (OR 1.99, 95% CI 1.24-3.19) in the average-risk screened population, and were 8.8 percent and 7.1 percent (OR 1.27, 95% CI 1.01-1.60) in diagnosed patients scheduled for colonoscopy. The sensitivity of iFOBT (0.67, 95% CI 0.61-0.73) was superior to that of gFOBT (0.54, 95% CI 0.48-0.60), as well as the specificities (0.85, 95% CI 0.83-0.87 vs 0.80, 95% CI 0.78-0.82) and positive predictive values (0.41 vs 0.29) in cohort trials of diagnosed patients. CONCLUSION: Our review suggests that iFOBT could perform better in increasing the detection rate of advanced colorectal neoplasm than gFOBT and possesses higher sensitivity and specificity in the surveillance of advanced colorectal neoplasm for patients. PMID- 20579219 TI - Prevalence and incidence rates of Crohn's disease in mainland China: a meta analysis of 55 years of research. AB - OBJECTIVES: To better understand the occurrence of Crohn's disease in mainland China and to give an updated overview of the current status of the disease. METHODS: We previously performed a computer-based literature search using 50 years of records from the Chinese Database of Biology and Medicine (1979 to 2002), combined with a manual year-by-year search of the literature from 1950 to 1978. Using a similar method, descriptive epidemiological data of the last 5 years (2003 to September 2007) were collected, pooled with our previous data and re-analyzed. RESULTS: In total, 3618 cases of Crohn's disease since 1950 have been reported from 29 provinces and cities in mainland China, comprising 2112 male and 1506 female patients, with a male predominance of 1.40:1. More than 75 percent of the patients were aged from 20 to 50 years old, with a mean age of 36.9 +/- 4.4 (1- 84) years. The extrapolated disease incidence and prevalence rates are 0.848/10(5) and 2.29/10(5) person/year, respectively. CONCLUSION: The incidence and prevalence rates of Crohn's disease have been increasing rapidly, and the disease is no longer uncommon in China, but these rates are still lower than those in developed countries and other Asian countries. An underestimation may occur because patients who were misdiagnosed or did not seek medical advice could not be included in the study. A future population-based survey is warranted. PMID- 20579220 TI - Differential gene and protein expression in primary gastric carcinomas and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis. AB - OBJECTIVE: To gain insight into the molecular events of lymph node metastasis of human gastric carcinoma. METHODS: The gene expression profile of five matched primary gastric carcinomas and their lymph node metastases was analyzed by complementary DNA (cDNA) microarray. Differential genes were identified in the metastatic and corresponding primary tumor pairs. Among the differentially expressed genes, carbonic anhydrase II (CAII) and insulin-like growth factor binding protein 4 (IGFBP 4) genes were detected by RT-PCR. CTTN protein expression was examined by tissue microarray. RESULTS: There was a high expression (over twofold) of 44 genes and a low expression (under twofold) of 32 genes in lymph node metastasis compared with primary gastric carcinoma, respectively. CAII mRNA was downregulated and IGFBP 4 mRNA was upregulated in paired lymph node metastases of gastric carcinomas. The overexpression of CTTN protein was related to the lymph node metastasis and the clinical stage of gastric carcinomas. CONCLUSION: This study showed that there is a low expression of genes relative to growth signal and immune response in lymph node metastases, and a high expression of genes relative to growth factor, cell cycle, cell motility and adhesion in lymph node metastases compared with primary gastric carcinomas. The expression of CTTN was related to the invasion and metastasis of gastric cancer. PMID- 20579221 TI - Knockdown of hTERT by SiRNA suppresses growth of Capan-2 human pancreatic cancer cell via the inhibition of expressions of Bcl-2 and COX-2. AB - OBJECTIVE: To investigate the effects of human telomerase reverse transcriptase (hTERT) on the growth of Capan-2 human pancreatic cancer cell and apoptosis. METHODS: Cell proliferation, apoptosis and cell cycle were analyzed by cell counting and flow cytometry. mRNA and protein expressions of hTERT, Bcl-2 and cyclooxygenase (COX)-2 were assessed by real time PCR and Western blot. RESULTS: Cell growth was significantly inhibited by 26.39 percent 24 h after hTERT-small interference RNA (siRNA) transfection (50 nmol/L) with a 100 percent silencing efficiency (P < 0.05). The inhibition rates of cell proliferation were 46.77 percent, 70.61 percent, 84.71 percent and 85.99 percent at 2, 3, 5 and 7 days after transfection, respectively (P < 0.001). Early and late apoptotic cells increased significantly (especially 24 h after transfection) (P < 0.001). The cell cycle was suppressed significantly as manifested by the increase of cells in the G0/G1 phase and the decrease of cells in the S phase and G2/M phase (P < 0.01). The expressions of Bcl-2 mRNA and COX-2 mRNA were inhibited significantly 48 h after transfection: the inhibition rates were 86.86 percent and 100 percent, respectively (P < 0.001). Levels of Bcl-2 protein were downregulated by 58.54 percent and 63.44 percent and the levels of COX-2 protein were downregulated by 50.06 percent and 82.77 percent at 48 h and 72 h after transfection, respectively. CONCLUSION: Knockdown of hTERT by siRNA can inhibit the growth of Capan-2 cell. The inhibitory effect is associated with the downregulation of Bcl 2 and COX-2. PMID- 20579222 TI - Exclusive enteral nutrition in the management of perianal Crohn's disease in children. PMID- 20579223 TI - Intestinal Penicillium marneffei: an unusual cause of chronic diarrhea in an AIDS patient. PMID- 20579224 TI - The significance of duodenal white spots. PMID- 20579226 TI - [S2k-guideline for therapy of acne]. AB - To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text. PMID- 20579227 TI - Nosocomial Staphylococcal scalded skin syndrome caused by intra-articular injection. AB - BACKGROUND: The pathogenic role of nasal carriage as a source for cutaneous and soft-tissue Staphylococcus aureus (SA) infections, and Staphylococcal scalded skin syndrome (SSSS) in particular, is unclear. OBSERVATION: We herein describe a nosocomial outbreak of SSSS in three orthopaedic patients who received intra articular injections by a single orthopaedic surgeon. Bacteriological samples from the index patients and medical personnel involved in their care were assessed by phage typing, polymerase chain reaction for exfoliative toxin genes, SmaI macro-restriction analysis and molecular spa-typing. These studies first revealed SA cultural growth in synovial fluid of all three patients as well as nasal mucosa of one medical assistant. Moreover, all SA isolates had the same phage typing and antibiotic susceptibilities and were positive for exfoliative toxin ETa by polymerase chain reaction. SmaI macro-restriction and spa-typing further confirmed all proband isolates to be identical. CONCLUSION: These findings provide evidence that SA nasal colonization of otherwise healthy carriers is a risk factor for SA infections, including SSSS, in predisposed individuals. PMID- 20579229 TI - Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility. AB - Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. PMID- 20579228 TI - Growth of Chrysomya megacephala (Fabricius) maggots in a morgue cooler. AB - In estimating the postmortem interval (PMI) using maggots obtained during autopsy, the forensic entomologist makes decisions regarding the effects of low temperature storage of the body on the insects. In this case report, a corpse was found in an abandoned house in the residential area of Bukit Mertajam, Penang, Malaysia. The maggots were found to be alive inside the mouth of the deceased although the corpse had been in the morgue cooler for 12 days. The maggots were reared and identified as Chrysomya megacephala (Fabricius). The emerged adult flies were kept as a stock colony, and the duration of development under the indoor fluctuating temperature regime was studied. The total duration of developmental process of this species was 9.5 +/- 0.5 days, and the PMI estimated was 3.2 +/- 0.6 days. This case report demonstrates the survival of Ch. megacephala maggots for 12 days and their growth inside the morgue cooler. PMID- 20579230 TI - Assessment of wear-related features of the kerf wall from saw marks in bone. AB - Analyses of saw marks in bone may yield important information about the class characteristics of saws used in postmortem dismemberments, yet little research has been directed at identifying saws' individualizing characteristics. This study adds to existing saw mark analysis methodologies by examining wear-related features of kerf walls using light- and environmental scanning electron microscopy. A crosscut saw and hacksaw were used to create sequences of 30 cuts in bone; these sequences reveal patterns of progressive loss of fine details of kerf wall morphology with increasing saw blade wear, because of the rounding of sharp points and edges. Nevertheless, diagnostic kerf wall features used to establish class characteristics persist despite these wear-related changes. Unsuccessful attempts at statistical analysis of wear-related changes, based on striae width and density, suggest these patterns are not readily quantifiable. Additionally, despite the scanning electron microscope's superior imaging capabilities, it provided few practical, methodological gains over traditional light microscopy. PMID- 20579231 TI - Trichophyton mentagrophytes perforates hair of adult corpses in the gaseous period. AB - Despite the substantial literature on mycology, there are still limited reports of the interaction between fungi and human hosts in the postmortem period. Thus, the main goal of this study was to investigate the in vitro perforation test using Trichophyton mentagrophytes on hair from adult corpses in the postmortem period (gaseous period). The protocol was carried out with positive (prepubescent children's hair) and negative controls (healthy adult hair) as well. One strain of Trichophyton rubrum was also used as a negative perforation control. Perforations were found in all the hair samples from corpses and prepubescent children after 12-14 days exposure to T. mentagrophytes and were absent in the hair samples of healthy adults. Furthermore, hair perforation was not observed with T. rubrum. Our preliminary findings suggest the use of T. mentagrophytes as a potential marker of the death interval in forensic science. PMID- 20579232 TI - The metamorphosis of managed care: implications for health reform internationally. AB - The conventional wisdom is that managed care's brief life is over and we are now in a post-managed care era. In fact, managed care has a long history and continues to thrive. Writers also often assume that managed care is a fixed thing. They overlook that managed care has evolved and neglect to examine the role that it plays in the health system. Furthermore, private actors and the state have used managed care tools to promote diverse goals. These include the following: increasing access to medical care; restricting physician entrepreneurialism; challenging professional control over the medical economy; curbing medical spending; managing medical practice and markets; furthering the growth of medical markets and private insurance; promoting for-profit medical facilities and insurers; earning bounties for reducing medical expenditures: and reducing governmental responsibility for, and oversight of, medical care. Struggles over these competing goals spurred the metamorphosis of managed care. This article explores how managed care transformed physicians' conflicts of interests and responses to them. It also examines how managed care altered the opportunities for patients/medical consumers to use exit and voice to spur change. PMID- 20579233 TI - Interpretation of the subjects' condition requirement: a legal perspective. AB - The U.S. Federal regulations allow institutional review boards (IRBs) to approve non-beneficial pediatric research when the risks are a minor increase over minimal, provided that the research is likely to develop generalizable knowledge about the subjects' disorder or condition. This "subjects' condition" requirement is quite controversial; commentators have argued for a variety of interpretations. Despite this considerable disagreement in the literature, there have not been any attempts to apply principles of legal interpretation to determine how the subjects' condition requirement should be understood. PMID- 20579234 TI - Diagnosing consciousness: neuroimaging, law, and the vegetative state. AB - In this paper, we review recent neuroimaging investigations of disorders of consciousness and different disciplines' understanding of consciousness itself. We consider potential tests of consciousness, their legal significance, and how they map onto broader themes in U.S. statutory law pertaining to advance directives and surrogate decision-making. In the process, we outline a taxonomy of themes to illustrate and clarify the variance in state-law definitions of consciousness. Finally, we discuss broader scientific, ethical, and legal issues associated with the advent of neuroimaging for disorders of consciousness and conclude with policy recommendations that could help to mitigate confusion in this realm. PMID- 20579235 TI - Damage control: unintended pregnancy in the United States military. AB - Women's access to reproductive health care is an ongoing source of conflict in U.S. politics; however, women in the military are often overlooked in these debates. Reproductive health care, including family planning, is a fundamental component of health care for women. Unintended pregnancy carries substantial health risks and financial costs, particularly for servicewomen. Compared with their civilian counterparts, women in the military experience greater challenges in preventing unwanted pregnancy and have less access to contraceptive services and abortion. Current military policies, federal laws, and health care practices are not always consistent with evidence-based research and patient-centered care. A multidisciplinary effort on the part of military personnel, lawmakers, and health care providers is needed to eliminate these disparities. We discuss recommendations in the following categories: improving contraceptive education and adherence, expanding research, broadening access to the full range of contraceptive options including emergency contraception, and ensuring access to safe abortion. PMID- 20579236 TI - Beyond the cold hit: measuring the impact of the national DNA data bank on public safety at the city and county level. AB - Over the past decade, the Combined DNA Index System (CODIS) has increased solvability of violent crimes by linking evidence DNA profiles to known offenders. At present, an in-depth analysis of the United States National DNA Data Bank effort has not assessed the success of this national public safety endeavor. Critics of this effort often focus on laboratory and police investigators unable to provide timely investigative support as a root cause(s) of CODIS' failure to increase public safety. By studying a group of nearly 200 DNA cold hits obtained in SFPD criminal investigations from 2001-2006, three key performance metrics (Significance of Cold Hits, Case Progression & Judicial Resolution, and Potential Reduction of Future Criminal Activity) provide a proper context in which to define the impact of CODIS at the City and County level. Further, the analysis of a recidivist group of cold hit offenders and their past interaction with law enforcement established five noteworthy criminal case resolution trends; these trends signify challenges to CODIS in achieving meaningful case resolutions. CODIS' effectiveness and critical activities to support case resolutions are the responsibility of all criminal justice partners in order to achieve long-lasting public safety within the United States. PMID- 20579237 TI - Currents in contemporary ethics. Should health care providers get treatment priority in an influenza pandemic? PMID- 20579238 TI - Teaching law and medicine on the interdisciplinary cutting edge: assisted reproductive technologies. PMID- 20579240 TI - Burton v. Florida: Maternal-fetal conflicts and medical decision-making during pregnancy. PMID- 20579241 TI - Law, science, and innovation: introduction to the symposium. PMID- 20579242 TI - Embryo stem cell research: ten years of controversy. AB - This overview of 10 years of stem cell controversy reviews the moral conflict that has made ESCs so controversial and how this conflict plays itself out in the legal realm, focusing on the constitutional status of efforts to ban ESC research or ESC-derived therapies. It provides a history of the federal funding debate from the Carter to the Obama administrations, and the importance of the Raab memo in authorizing federal funding for research with privately derived ESCs despite the Dickey-Wicker ban on federal funding of embryo research. It also reviews the role that scientists themselves have played in developing regulations for ESC research, the emergence of ESCROs as special review bodies for ESC research, and the thorough consent requirements for donation of IVF embryos to ESC research. With research now transitioning from the lab to the clinic, the article reviews the challenges of ensuring safety and consent in translational research. It concludes with a call for respecting those persons who have to using or working with ESC products and an account of how obtaining stem cells from a person's own cells will alleviate some but not all of the controversy surrounding ESC research. PMID- 20579243 TI - Why scientific details are important when novel technologies encounter law, politics, and ethics. AB - This paper focuses on the issue of what to do if a couple who generates embryos chooses to lawfully, and in their (and my) view, ethnically discard those embryos. Specifically, is it appropriate to use the cells that come from "excess" embryos in medical research instead of discarding them when a couple has ceased trying to have any additional children? PMID- 20579244 TI - Old and new ethics in the stem cell debate. AB - The debate about embryonic stem cell research is a conflict not between "religion" and "science," but between two ethical approaches to the dignity of human beings. The newer, more pragmatic ethic is not necessarily more conducive to rapid medical progress as is often assumed. PMID- 20579245 TI - Political interventions in U.S. human embryo research: an ethical assessment. AB - For more than 30 years, beginning with the Reagan administration's refusal to support and provide oversight for embryo research, and continuing to the present in congressionally imposed limits on funding for such research, progress in infertility medicine and the development of stem cell therapies has been seriously delayed by a series of political interventions. In almost all cases, these interventions result from a view of the moral status of human embryo premised largely on religious assumptions. Although some believe that these interventions are valid expressions of religious values in the public sector, it is argued here that they, in fact, contradict Rawls's conception of public reasoning. Both the prohibition of research involving the human embryo as well as bans on federal funding for embryo-related research place the particular religious views of some citizens above the pressing health needs of almost all, and thus violate the ideal of civility implicit in the Rawlsian standard. PMID- 20579246 TI - Creating embryos for use in stem cell research. AB - In this paper I will address whether the restriction on the creation of human embryos solely for the purpose of research in which they will be used and destroyed in the creation of human stem cell lines is ethically justified. Of course, a cynical but perhaps accurate reading of the new Obama policy is that leaving this restriction in place was done for political, not ethical, reasons, in light of the apparent public opposition to creating embryos for use in this research. But the issue of whether the restriction is ethically justified remains important, even if only for another day in the policy arena. PMID- 20579247 TI - Chimeras, moral status, and public policy: implications of the abortion debate for public policy on human/nonhuman chimera research. AB - Researchers are increasingly interested in creating chimeras by transplanting human embryonic stem cells (hESCs) into animals early in development. One concern is that such research could confer upon an animal the moral status of a normal human adult but then impermissibly fail to accord it the protections it merits in virtue of its enhanced moral status. Understanding the public policy implications of this ethical conclusion, though, is complicated by the fact that claims about moral status cannot play an unfettered role in public policy. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras. PMID- 20579248 TI - Reflections on governance models for the clinical translation of stem cells. AB - Governance models for the oversight of human embryonic stem cell research have been proposed which mirror in large part familiar oversight mechanisms for research with human subjects and non-human animals. While such models are in principle readily endorsable, there are a set of concerns related to their implementation--such as ensuring that an elaborated informed consent process and conducting long-term monitoring of research subjects are tenable--which suggest areas where gathering data may facilitate more appropriate oversight. In addition, it is unclear whether a new governance model based at individual institutions are sufficient to address the ethical issues inherent to this research. Regardless, some of the concerns that have arisen in considering the appropriate governance of stem cell research, particularly the important translational pathway of innovation in contrast to staged research, transparency and publication, and social justice, may be useful in science and translational research more broadly. PMID- 20579250 TI - Translating stem cell research: challenges at the research frontier. AB - This paper will address the translation of basic stem cell research into clinical research. While "stem cell" trials are sometimes used to describe established practices of bone marrow transplantation or transplantation of primary cells derived from bone marrow, for the purposes of this paper, I am primarily focusing on stem cell trials which are far less established, including use of hESC derived stem cells. The central ethical challenges in stem cell clinical trials arise in frontier research, not in standard, well-established areas of research. PMID- 20579249 TI - Resolving ethical issues in stem cell clinical trials: the example of Parkinson disease. AB - Clinical trials of stem cell transplantation raise ethical issues that are intertwined with scientific and design issues, including choice of control group and intervention, background interventions, endpoints, and selection of subjects. We recommend that the review and IRB oversight of stem cell clinical trials should be strengthened. Scientific and ethics review should be integrated in order to better assess risks and potential benefits. Informed consent should be enhanced by assuring that participants comprehend key aspects of the trial. For the trial to yield generalizable knowledge, negative findings and serious adverse events must be reported. PMID- 20579251 TI - Allowing innovative stem cell-based therapies outside of clinical trials: ethical and policy challenges. AB - This paper discusses exceptional circumstances under which patients outside of clinical trials are likely to receive innovative stem cell-based interventions. These circumstances involve: (1) stem cell interventions not initially amenable to a clinical trials approach; (2) expanded access to investigational stem cell products ("compassionate use"); and (3) off-label uses of FDA approved stem cell products. This paper proposes a new approach to regulating these exceptional cases. PMID- 20579252 TI - Overseeing innovative therapy without mistaking it for research: a function-based model based on old truths, new capacities, and lessons from stem cells. AB - Should innovative therapy occur only within a research paradigm and under institutional review board oversight? The health risks from current human embryonic stem cell clinical applications have raised again a fundamental question addressed first in papers submitted to inform the writing of the Belmont Report. Revisiting the thinking underlying the Belmont Report, together with examining changed circumstances since then, leads to a new model for overseeing innovative therapy based on its unique risks and context, important changes since the Belmont Report, and new opportunities for addressing risks through safety and quality systems in health care. PMID- 20579253 TI - Stem cell research and economic promises. AB - In the context of stem cell research, the promise of economic growth has become a common policy argument for adoption of permissive policies and increased government funding. However, declarations of economic and commercial benefit, which can be found in policy reports, the scientific literature, public funding policies, and the popular press, have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the researchers who must work under its shadow? PMID- 20579254 TI - WARF's stem cell patents and tensions between public and private sector approaches to research. AB - While society debates whether and how to use public funds to support work on human embryonic stem cells (hESCs), many scientific groups and businesses debate a different question - the extent to which patents that cover such stem cells should be permitted to limit or to tax their research. The Wisconsin Alumni Research Foundation (WARF), a non-profit foundation that manages intellectual property generated by researchers at the University of Wisconsin at Madison, owns three patents that have been at the heart of the latter controversy The story of WARF's patents and the controversy they have fostered highlights not only continuing tensions between proprietary and nonproprietary approaches to developing science and technology, but also an at least partly reassuring capacity of public and private sectors to deal with those tensions in a way that can render them substantially manageable, and frequently more manageable as a technology matures. More particularly, the cumulative story of WARF's patents features three leitmotifs that suggest how an attentive and engaged public sector might commonly succeed in working with public and private sector actors to achieve workable balances between proprietary rights and more general social interests: (1) right holders' decisions to pursue less than full rights assertion or enforcement; (2) the ability of government and other public sector actors to help bring about such decisions through co-option or pressure; and (3) the frequent availability or development of technological alternatives that limit research bottlenecks. PMID- 20579256 TI - Will embryonic stem cells change health policy? AB - Embryonic stem cells are actively debated in political and public policy arenas. However, the connections between stem cell innovation and overall health care policy are seldom elucidated. As with many controversial aspects of medical care, the stem cell debate bridges to a variety of social conversations beyond abortion. Some issues, such as translational medicine, commercialization, patient and public safety, health care spending, physician practice, and access to insurance and health care services, are core health policy concerns. Other issues, such as economic development, technologic progress, fiscal politics, and tort reform, are only indirectly related to the health care system but are frequently seen through a health care lens. These connections will help determine whether the stem cell debate reaches a resolution, and what that resolution might be. PMID- 20579255 TI - Stem cell research as innovation: expanding the ethical and policy conversation. AB - Research using human embryonic stem cells raises an array of complex ethical issues, including, but by no means limited to, the moral status of developing human life. Unfortunately much of the public discussion fails to take into account this complexity. Advocacy for liberal and conservative positions on human embryonic stem cell research can be simplistic and misleading. Ethical concepts such as truth-telling, scientific integrity, and social justice should be part of the debate over federal support for human embryonic stem cell research. Moreover, the debate should be conducted in accord with principles of deliberative democracy, including respect for people holding competing views. PMID- 20579257 TI - NanoSIMS imaging of Bacillus spores sectioned by focused ion beam. AB - Preparation and sectioning of bacterial spores by focused ion beam and subsequent high resolution secondary ion mass spectrometry analytical imaging is demonstrated. Scanning transmission electron microscopy mode imaging in a scanning electron microscope is used to show that the internal structure of the bacterial spore can be preserved during focused ion beam sectioning and can be imaged without contrast staining. Ion images of the sections show that the internal elemental distributions of the sectioned spores are preserved. A rapid focused ion beam top-sectioning method is demonstrated to yield comparable ion images without the need for sample trenching and section lift-out. The lift-out and thinning method enable correlated transmission electron microscopy and high resolution secondary ion mass spectrometry analyses. The top-cutting method is preferable if only secondary ion mass spectrometry analyses are performed because this method is faster and yields more sample material for analysis; depth of useful sample material is approximately 300 nm for top-cut sections versus approximately 100 nm for electron-transparent sections. PMID- 20579259 TI - Characterizing voltage contrast in photoelectron emission microscopy. AB - A non-destructive technique for obtaining voltage contrast information with photoelectron emission microscopy is described. Samples consisting of electrically isolated metal lines were used to quantify voltage contrast in photoelectron emission microscopy. The voltage contrast behaviour is characterized by comparing measured voltage contrast with calculated voltage contrast from two electrostatic models. Measured voltage contrast was found to agree closely with the calculated voltage contrast, demonstrating that voltage contrast in photoelectron emission microscopy can be used to probe local voltage information in microelectronic devices in a non-intrusive fashion. PMID- 20579258 TI - Combining FIB milling and conventional Argon ion milling techniques to prepare high-quality site-specific TEM samples for quantitative EELS analysis of oxygen in molten iron. AB - This paper reports a procedure to combine the focused ion beam micro-sampling method with conventional Ar-milling to prepare high-quality site-specific transmission electron microscopy cross-section samples. The advantage is to enable chemical and structural evaluations of oxygen dissolved in a molten iron sample to be made after quenching and recovery from high-pressure experiments in a laser-heated diamond anvil cell. The evaluations were performed by using electron energy-loss spectroscopy and high-resolution transmission electron microscopy. The high signal to noise ratios of electron energy-loss spectroscopy core-loss spectra from the transmission electron microscopy thin foil, re-thinned down to 40 nm in thickness by conventional Argon ion milling, provided us with oxygen quantitative analyses of the quenched molten iron phase. In addition, we could obtain lattice-fringe images using high-resolution transmission electron microscopy. The electron energy-loss spectroscopy analysis of oxygen in Fe(0.94)O has been carried out with a relative accuracy of 2%, using an analytical procedure proposed for foils thinner than 80 nm. Oxygen K-edge energy-loss near edge structure also allows us to identify the specific phase that results from quenching and its electronic structure by the technique of fingerprinting of the spectrum with reference spectra in the Fe-O system. PMID- 20579260 TI - Automatic twin statistics from electron backscattered diffraction data. AB - A new computer code has been developed to automatically extract quantitative twin statistics from electron backscatter diffraction data. The new code is an improvement upon previous codes in that it handles materials of any crystal symmetry, type I, Type II and compound twins, and general stress states. Moreover, accuracy of the results has been greatly improved. In addition, twin statistics including number, area fraction, twin thickness and twinning dependencies on orientation, grain size and neighbourhood effects can be routinely analysed. The new code has been applied to scan data from deformed magnesium, zirconium and uranium, and can potentially be used for any twinning material for which reliable electron backscatter diffraction results can be obtained. PMID- 20579261 TI - Regularized phase tomography enables study of mineralized and unmineralized tissue in porous bone scaffold. AB - Regularized phase tomography was used to image non-calcified fibrous matrix in in vitro cell-cultivated porous bone scaffold samples. 3D micro-architecture of bone and bone scaffold has previously been studied by micro-computed tomography, synchrotron radiation (SR) micro-computed tomography and microdiffraction. However, neither of these techniques can resolve the low-calcified immature pre bone fibrous structures. Skelite porous scaffold discs were seeded with osteoblasts, a combination of osteoblast and pre-osteoclasts and, as controls, with pre-osteoclasts only, and then cultivated for 8 weeks. They were subsequently imaged using SR propagation-based phase contrast imaging. Reconstructions using a regularized holographic phase tomography approach were compared to standard (absorption) SR micro-computed tomography, which show that quantitative analysis, such as volume and thickness measurements, of both the calcified fraction and the immature bone matrix in the reconstructed volumes is enabled. Indications of the effect of this type of culture on Skelite, such as change in mineralization and deposit of mature bone on the walls of the scaffold, are found. The results are verified with a histological study. PMID- 20579263 TI - Four-dimensional telomere analysis in recordings of living human cells acquired with controlled light exposure microscopy. AB - Telomeres are the complex end structures that confer functional integrity and positional stability to human chromosomes. Telomere research has long been dominated by length measurements and biochemical analyses. Recently, interest has shifted towards the role of their three-dimensional organization and dynamics within the nuclear volume. In the mammalian interphase nucleus, there is increasing evidence for a telomeric configuration that is non-random and is cell cycle and cell type dependent. This has functional implications for genome stability. Objective and reproducible representation of the spatiotemporal organization of telomeres, under different experimental conditions, requires quantification by reliable automated image processing techniques. In this paper, we describe methods for quantitative telomere analysis in cell nuclei of living human cells expressing telomere-binding fusion proteins. We present a toolbox for determining telomere positions within the nucleus with subresolution accuracy and tracking telomeres in 4D controlled light exposure microscopy (CLEM) recordings. The use of CLEM allowed for durable imaging and thereby improved segmentation performance considerably. With minor modifications, the underlying algorithms can be expanded to the analysis of other intranuclear features, such as nuclear bodies or DNA double stranded break foci. PMID- 20579262 TI - An improved strip FRAP method for estimating diffusion coefficients: correcting for the degree of photobleaching. AB - Fluorescence recovery after photobleaching is a widely established method for the estimation of diffusion coefficients, strip bleaching with an associated recovery curve analysis being one of the simplest techniques. However, its implementation requires near 100% bleaching in the region of interest with negligible fluorescence loss outside, both constraints being hard to achieve concomitantly for fast diffusing molecules. We demonstrate that when these requirements are not met there is an error in the estimation of the diffusion coefficient D, either an under- or overestimation depending on which assumption is violated the most. We propose a simple modification to the recovery curve analysis incorporating the concept of the relative bleached mass m giving a revised recovery time parametrization tau=m(2)w(2)/4piD for a strip of width w. This modified model removes the requirement of 100% bleaching in the region of interest and allows for limited diffusion of the fluorophore during bleaching. We validate our method by estimating the (volume) diffusion coefficient of FITC-labelled IgG in 60% glycerol solution, D= 4.09 +/- 0.21 microm(2) s(-1), and the (surface) diffusion coefficient of a green-fluorescent protein-tagged class I MHC protein expressed at the surface of a human B cell line, D= 0.32 +/- 0.03 microm(2) s(-1) for a population of cells. PMID- 20579264 TI - Quantitative analysis and modelling of hepatic iron stores using stereology and spatial statistics. AB - Hepatic iron overload is a common clinical problem resulting from hyperabsorption syndromes and from chronic transfusion therapy. Not only does iron loading vary between reticuloendothelial stores and hepatocytes, but iron is heterogeneously distributed within hepatocytes as well. Since the accessibility of iron particles to chelation may depend, in part, on their distribution, we sought to characterize the shape and scale of iron deposition in humans with transfusional iron overload. Toward this end, we performed a histological analysis of iron stores in liver biopsy specimens of 20 patients (1.3-57.8 mg iron/g dry tissue weight) with aid of electron and light microscopy. We estimated distributions related to variability in siderosomal size, proximity of iron centres and inter cellular iron loading. These distributions could be well modelled by Gamma distribution functions over most of the pathologic range of iron concentrations. Thus, for a given liver iron burden, a virtual iron-overloaded liver could be created that served as a model for the true histologic appearance. Such a model may be helpful for understanding the mechanics of iron loading or in predicting response to iron removal therapy. PMID- 20579265 TI - Three-dimensional analysis of intermediate filament networks using SEM tomography. AB - We identified tomographic reconstruction of a scanning electron microscopy tilt series recording the secondary electron signal as a well-suited method to generate high-contrast three-dimensional data of intermediate filament (IF) networks in pancreatic cancer cells. Although the tilt series does not strictly conform to the projection requirement of tomographic reconstruction, this approach is possible due to specific properties of the detergent-extracted samples. We introduce an algorithm to extract the graph structure of the IF networks from the tomograms based on image analysis tools. This allows a high resolution analysis of network morphology, which is known to control the mechanical response of the cells to large-scale deformations. Statistical analysis of the extracted network graphs is used to investigate principles of structural network organization which can be linked to the regulation of cell elasticity. PMID- 20579266 TI - Segmentation of 3D microtomographic images of granular materials with the stochastic watershed. AB - Segmentation of 3D images of granular materials obtained by microtomography is not an easy task. Because of the conditions of acquisition and the nature of the media, the available images are not exploitable without a reliable method of extraction of the grains. The high connectivity in the medium, the disparity of the object's shape and the presence of image imperfections make classical segmentation methods (using image gradient and watershed constrained by markers) extremely difficult to perform efficiently. In this paper, we propose a non parametric method using the stochastic watershed, allowing to estimate a 3D probability map of contours. Procedures allowing to extract final segmentation from this function are then presented. PMID- 20579267 TI - Principles of depth-resolved Kikuchi pattern simulation for electron backscatter diffraction. AB - This paper presents a tutorial discussion of the principles underlying the depth dependent Kikuchi pattern formation of backscattered electrons in the scanning electron microscope. To illustrate the connections between various electron diffraction methods, the formation of Kikuchi bands in electron backscatter diffraction in the scanning electron microscope and in transmission electron microscopy are compared with the help of simulations employing the dynamical theory of electron diffraction. The close relationship between backscattered electron diffraction and convergent beam electron diffraction is illuminated by showing how both effects can be calculated within the same theoretical framework. The influence of the depth-dependence of diffuse electron scattering on the formation of the experimentally observed electron backscatter diffraction contrast and intensity is visualized by calculations of depth-resolved Kikuchi patterns. Comparison of an experimental electron backscatter diffraction pattern with simulations assuming several different depth distributions shows that the depth-distribution of backscattered electrons needs to be taken into account in quantitative descriptions. This should make it possible to obtain more quantitative depth-dependent information from experimental electron backscatter diffraction patterns via correlation with dynamical diffraction simulations and Monte Carlo models of electron scattering. PMID- 20579268 TI - High temperature AFM study of CAP 30/45 pen grade bitumen. AB - Bitumen is a complex mixture of hydrocarbons for which microstructural understanding is incomplete. In an effort to detail this microstructure, a asphalt cement sample (CAP 30/45) was analysed by thermal phase detection atomic force microscopy. Phase contrast and topography images showed that sample morphology is highly dependent on temperature. The 'bee structure' changed considerably at temperatures between 50 degrees C and 56 degrees C. A decrease of the oscillation amplitude was observed upon heating and the 'bees' completely disappeared at temperatures above 57 degrees C. When the temperature was decreased after melting at 170 degrees C, the 'bees' began to nucleate gradually at temperatures of 57 degrees C and its evolution with time was followed. Changes in morphology were compared to thermal analysis results and a model for the 'bee' structure was proposed. PMID- 20579269 TI - One-stop stereology: the estimation of 3D parameters using isotropic rulers. AB - The stereological estimation of second-order descriptors of spatial architecture appears to be inherently more time-consuming and labour-intensive than the estimation of first-order quantities (total quantities or ratios). Therefore, far fewer researchers tend to make use of second-order approaches in their stereological research projects. In this paper, we use a tutorial approach to illustrate how a desire for practical simplicity has provided us with a data collection method that can be used to simultaneously estimate both first-order and second-order properties of the microstructure of a defined anatomical feature of an organ. The approach does not rely on new results from theory, but nevertheless allows either isotropic uniform random or vertical uniform random sections to be used to make estimates of a comprehensive list of 10 microstructural parameters using relationships that are well known in the literature. The probe used in all cases is an isotropically distributed Ruler and the data collection protocol is easy to learn and apply. We illustrate the method on brain tissue but emphasize that the approach can also be applied to non biological material. PMID- 20579270 TI - Formation and reduction of streak artefacts in electron tomography. AB - We have analysed the formation of streak artefacts in the reconstruction based on the filtered back projection algorithm in electron tomography (ET) and accordingly applied an adaptive interpolation technique to artefact reduction. In the adaptive interpolation to recover the missing information, the edge positions in a projection curve were tracked to reduce the interpolation error. A simulation was used to demonstrate the effectiveness of the artefact reduction. Furthermore, image reconstruction of integrated circuit specimens in the ET experiments with the ultra-high voltage electron microscope show that the strong streak artefacts can be reduced effectively by our artefact reduction technique. PMID- 20579271 TI - Clustering and nearest neighbour distances in atom probe tomography: the influence of the interfaces. AB - The statistical 1NN method is an elegant way to derive the composition of small B enriched clusters in a random AB solid solution from 3D atomic fields. An extension of this method is proposed that includes the contribution of interface region and provides an estimate of the core composition of clusters. This model is applied to boron-implanted silicon containing boron-enriched clusters. A comparison with the previous model is performed. This new approach gives relevant information, i.e. the core composition of clusters and the cluster-matrix interface width. PMID- 20579272 TI - Spine micromorphology of normal and hyperhydric Mammillaria gracilis Pfeiff. (Cactaceae) shoots. AB - Artificial conditions of tissue culture affect growth and physiology of crassulacean acid metabolism plants which often results in formation of hyperhydric shoots. In in vitro conditions Mammillaria gracilis Pfeiff. (Cactaceae) growth switches from organized to unorganized way, producing a habituated organogenic callus which simultaneously regenerates morphologically normal as well as altered hyperhydric shoots. In this study, influence of tissue culture conditions on morphology of cactus spines of normal and hyperhydric shoots was investigated. Spines of pot-grown Mammillaria plants and of in vitro regenerated shoots were examined with stereo microscope and scanning electron microscope. The pot-grown plants had 16-17 spines per areole. In vitro grown normal shoots, even though they kept typical shoot morphology, had lower number of spines (11-12) and altered spine morphology. This difference was even more pronounced in spine number (six to seven) and morphology of the hyperhydric shoots. Scanning electron microscopy analysis revealed remarkable differences in micromorphology of spine surface between pot-grown and in vitro grown shoots. Spines of in vitro grown normal shoots showed numerous long trichomes, which were more elongated on spines of the hyperhydric shoots; the corresponding structures on spine surface of pot-grown plants were noticed only as small protrusions. Scanning electron microscopy morphometric studies showed that the spines of pot grown plants were significantly longer compared to the spines of shoots grown in tissue culture. Moreover, transverse section shape varies from elliptical in pot grown plants to circular in normal and hyperhydric shoots grown in vitro. Cluster and correspondence analyses performed on the scanning electron microscope obtained results suggest great variability among spines of pot-grown plants. Spines of in vitro grown normal and hyperhydric shoots showed low level of morphological variation among themselves despite the significant difference in shoot morphology. PMID- 20579273 TI - Membrane domains in CNS physiology and pathology. Abstracts of the Fourth International Society for Neurochemistry (ISN) Special Conference. Erice (Trapani), Sicily, Italy, 22-26 May 2010. PMID- 20579274 TI - Abstracts of the Joint Meeting of the Italian Peripheral Nerve Study Group and the British Peripheral Nerve Society. Trieste, Italy. April 8-10, 2010. PMID- 20579275 TI - Modified split-cast technique: a new, timesaving clinical remount technique. AB - Interocclusal discrepancies can be eliminated by a clinical remount procedure, but most practitioners avoid it because of the time involved. This article introduces a new timesaving method, the modified split-cast technique. It uses a semi-adjustable articulator, tin foil as plaster separator, and an addition-type, silicone bite-registration material. The technician does most of the remounting procedures before the denture delivery appointment, so the dentist spends very little time chairside to complete the clinical remount procedure. Compared with the conventional and two other remounting techniques, the new technique is faster and easier to manipulate. PMID- 20579276 TI - Patient preferences and assessment of likely adherence to hepatitis C virus treatment. AB - To estimate patient preferences for attributes of hepatitis C virus (HCV) treatment and patients' assessment of the likely effect of treatment attributes on treatment adherence, HCV patients >=18 years old completed an online survey that included nine 2-alternative choice questions. Each choice question was defined by the probability of sustained viral response (Efficacy), injection frequency (Frequency), duration of flu-like symptoms after every injection (Flu), injection device (Device), average number of days of work missed each week (Lost Work Days), probability of reversible hair thinning while on treatment (Alopecia) and probability of developing clinical depression while on treatment (Depression). We estimated a mean relative importance weight for each attribute. Patients also answered three rating questions to assess the extent to which treatment attributes might affect adherence. Hundred and fifty patients completed the survey. Efficacy was the most important attribute with a mean relative importance weight of 10 [95% CI: 7.9-12.1]. The remaining attributes were ranked in order of importance as follows: Depression (4.4 [95% CI: 3.6-5.1]), Flu Days(Frequency*Flu) (3.7 [95% CI: 2.2-5.3]), Lost Work Days (2.9 [95% CI: 2.3 3.5]), Alopecia (1.3 [95% CI: 0.7-1.9]) and Device (1.2 [95% CI: 0.4-2.0]). Patients with prior treatment experience were less likely to indicate that treatment attributes would affect adherence. Patients also indicated that increases in the number of flu days would increase the likelihood of nonadherence to treatment. Sustained viral response is the most important treatment attribute to patients but treatment side effects might affect treatment adherence. PMID- 20579277 TI - Study of cellular immune response against Hepatitis E virus (HEV). AB - Hepatitis E virus infection (HEV) is a major cause of acute viral hepatitis in the developing world. The immunopathology of HEV infections has not yet been elucidated. The virus is noncytopathic, and therefore, liver injury may be attributed to immune-mediated damage by cytotoxic T cells and natural killer cells. Therefore, we studied the nature of immune cells involved in HEV-induced liver damage using immunohistochemistry in liver biopsies taken from patients with HEV-induced acute liver failure and demonstrated a significant infiltration of activated CD8(+) T cells containing granzymes. These findings suggest the possible involvement of cytotoxic T cells in disease pathogenesis during HEV infection. PMID- 20579278 TI - Hepatitis C virus enters human peripheral neuroblastoma cells - evidence for extra-hepatic cells sustaining hepatitis C virus penetration. AB - Patients with chronic hepatitis C virus (HCV) infection show an increased incidence of nervous system disorders such as chronic fatigue syndrome, depression and cognitive dysfunction. It is unclear whether this is because of HCV replication in the brain and in peripheral neuronal cells or to more indirect effects of HCV infection on the central or peripheral nervous system. The aim of this study was to investigate whether cells originating from these tissues are permissive for HCV cell entry, RNA replication and virus assembly. Among eight cell lines analysed, the human peripheral neuroblastoma cell line SKNMC expressed all HCV entry factors and was efficiently infected with HCV pseudoparticles (HCVpp) independent of the HCV genotype. All remaining cell types including human neuroblastoma and glioblastoma cell lines and microglial cells lacked expression of at least one host factor essential for HCV entry. When transfected with HCV luciferase reporter virus RNA, inoculated with HCV reporter viruses or challenged with high-titre cell culture-derived HCV, none of these cells supported detectable HCV RNA replication. Thus, in conclusion, this comprehensive screening did not reveal evidence directly strengthening the notion that HCV enters and replicates in the central nervous system. However, productive viral entry into the peripheral neuroblastoma cell line SKNMC indicates that HCV may penetrate into certain nonhepatic cell types which may serve as viral reservoirs and could modulate viral pathogenesis. PMID- 20579280 TI - The reorientation of public health research. PMID- 20579281 TI - Where is the future in public health? AB - CONTEXT: Today's societies have far-reaching impacts on future conditions for health. Against this backdrop, this article explores how the future is represented in contemporary public health, examining both its conceptual base and influential approaches through which evidence is generated for policy. METHODS: Mission statements and official reviews provide insight into how the future is represented in public health's conceptual and ethical foundations. For its research practices, the article takes examples from epidemiological, intervention, and economic research, selecting risk-factor epidemiology, randomized controlled trials, and economic evaluation as exemplars. FINDINGS: Concepts and ethics suggest that public health research and policy will be concerned with protecting both today's and tomorrow's populations from conditions that threaten their health. But rather than facilitating sustained engagement with future conditions and future health, exemplary approaches to gathering evidence focus on today's population. Thus, risk-factor epidemiology pinpoints risks in temporal proximity to the individual; controlled trials track short-term effects of interventions on the participants' health; and economic evaluations weigh policies according to their value to the current population. While their orientation to the present and near future aligns well with the compressed timescales for policy delivery on which democratic governments tend to work, it makes it difficult for the public health community to direct attention to conditions for future health. CONCLUSIONS: This article points to the need for research perspectives and practices that, consistent with public health's conceptual and ethical foundations, represent the interests of both tomorrow's and today's populations. PMID- 20579282 TI - Making the case for laws that improve health: a framework for public health law research. AB - CONTEXT: Public health law has received considerable attention in recent years and has become an essential field in public health. Public health law research, however, has received less attention. METHODS: Expert commentary. FINDINGS: This article explores public health law research, defined as the scientific study of the relation of law and legal practices to population health. The article offers a logic model of public health law research and a typology of approaches to studying the effects of law on public health. Research on the content and prevalence of public health laws, processes of adopting and implementing laws, and the extent to which and mechanisms through which law affects health outcomes can use methods drawn from epidemiology, economics, sociology, and other disciplines. The maturation of public health law research as a field depends on methodological rigor, adequate research funding, access to appropriate data sources, and policymakers' use of research findings. CONCLUSIONS: Public health law research is a young field but holds great promise for supporting evidence based policy making that will improve population health. PMID- 20579284 TI - "Impactibility models": identifying the subgroup of high-risk patients most amenable to hospital-avoidance programs. AB - CONTEXT: Predictive models can be used to identify people at high risk of unplanned hospitalization, although some of the high-risk patients they identify may not be amenable to preventive care. This study describes the development of "impactibility models," which aim to identify the subset of at-risk patients for whom preventive care is expected to be successful. METHODS: This research used semistructured interviews with representatives of thirty American organizations that build, use, or appraise predictive models for health care. FINDINGS: Impactibility models may refine the output of predictive models by (1) giving priority to patients with diseases that are particularly amenable to preventive care; (2) excluding patients who are least likely to respond to preventive care; or (3) identifying the form of preventive care best matched to each patient's characteristics. CONCLUSIONS: Impactibility models could improve the efficiency of hospital-avoidance programs, but they have important implications for equity and access. PMID- 20579283 TI - The evolution of health care advance planning law and policy. AB - CONTEXT: The legal tools of health care advance planning have substantially changed since their emergence in the mid-1970s. Thirty years of policy development, primarily at the state legislative level addressing surrogate decision making and advance directives, have resulted in a disjointed policy landscape, yet with important points of convergence evolving over time. An understanding of the evolution of advance care planning policy has important implications for policy at both the state and federal levels. METHODS: This article is a longitudinal statutory and literature review of health care advance planning from its origins to the present. FINDINGS: While considerable variability across the states still remains, changes in law and policy over time suggest a gradual paradigm shift from what is described as a "legal transactional approach" to a "communications approach," the most recent extension of which is the emergence of Physician Orders for Life-Sustaining Treatment, or POLST. The communications approach helps translate patients' goals into visible and portable medical orders. CONCLUSIONS: States are likely to continue gradually moving away from a legal transactional mode of advance planning toward a communications model, albeit with challenges to authentic and reliable communication that accurately translates patients' wishes into the care they receive. In the meantime, the states and their health care institutions will continue to serve as the primary laboratory for advance care planning policy and practice. PMID- 20579287 TI - Parallel polyploid speciation: distinct sympatric gene-pools of recurrently derived allo-octoploid Asplenium ferns. AB - Although polyploidy is widespread, its significance to the generation of biodiversity remains unclear. Many polyploids have been derived recurrently. For a particular polyploid, gene-flow between the products of independent origin is typical where they come into contact. Here, we use AFLP DNA-fingerprinting and chloroplast DNA sequences to demonstrate parallel polyploid speciation within both of the ferns Asplenium cimmeriorum and A. gracillimum. Both of these taxa comprise at least two allopolyploids, recurrently derived from the same progenitor pair. Each of these allopolyploids remain genetically distinguishable even with extensive sympatry, and could therefore be considered distinct species. To our knowledge, parallel speciation on this scale amongst recurrent polyploids has not been previously reported. With their parallel origins, these 'evolutionary replicates' provide an unrivalled opportunity to investigate how the reproductive barriers and ecological differentiation necessary for speciation arise following polyploidy. PMID- 20579285 TI - EBM, HTA, and CER: clearing the confusion. AB - CONTEXT: The terms evidence-based medicine (EBM), health technology assessment (HTA), comparative effectiveness research (CER), and other related terms lack clarity and so could lead to miscommunication, confusion, and poor decision making. The objective of this article is to clarify their definitions and the relationships among key terms and concepts. METHODS: This article used the relevant methods and policy literature as well as the websites of organizations engaged in evidence-based activities to develop a framework to explain the relationships among the terms EBM, HTA, and CER. FINDINGS: This article proposes an organizing framework and presents a graphic demonstrating the differences and relationships among these terms and concepts. CONCLUSIONS: More specific terminology and concepts are necessary for an informed and clear public policy debate. They are even more important to inform decision making at all levels and to engender more accountability by the organizations and individuals responsible for these decisions. PMID- 20579288 TI - Genetic effective size, N(e), tracks density in a small freshwater cyprinid, Pecos bluntnose shiner (Notropis simus pecosensis). AB - Genetic monitoring tracks changes in measures of diversity including allelic richness, heterozygosity and genetic effective size over time, and has emerged as an important tool for understanding evolutionary consequences of population management. One proposed application of genetic monitoring has been to estimate abundance and its trajectory through time. Here, genetic monitoring was conducted across five consecutive year for the Pecos bluntnose shiner, a federally threatened minnow. Temporal changes in allele frequencies at seven microsatellite DNA loci were used to estimate variance effective size (N(eV)) across adjacent years in the time series. Likewise, effective size was computed using the linkage disequilibrium method (N(eD)) for each sample. Estimates of N(e) were then compared to estimates of adult fish density obtained from traditional demographic monitoring. For Pecos bluntnose shiner, density (catch-per-unit-effort), N(eV) and N(eD) were positively associated across this time series. Results for Pecos bluntnose shiner were compared to a related and ecologically similar species, the Rio Grande silvery minnow. In this species, density and N(eV) were negatively associated, which suggested decoupling of abundance and effective size trajectories. Conversely, density and N(eD) were positively associated. For Rio Grande silvery minnow, discrepancies among estimates of N(e) and their relationships with adult fish density could be related to effects of high variance in reproductive success in the wild and/or effects of supplementation of the wild population with captive-bred and reared fish. The efficacy of N(e) as a predictor of density and abundance may depend on intrinsic population dynamics of the species and how these dynamics are influenced by the landscape features, management protocols and other factors. PMID- 20579289 TI - Ancient genome-wide admixture extends beyond the current hybrid zone between Macaca fascicularis and M. mulatta. AB - Macaca fascicularis and Macaca mulatta are two of the most commonly used laboratory macaques, yet their genetic differences at a genome-wide level remain unclear. We analysed the multilocus DNA sequence data of 54 autosomal loci obtained from M. fascicularis samples from three different geographic origins and M. mulatta samples of Burmese origin. M. fascicularis shows high nucleotide diversity, four to five times higher than humans, and a strong geographic population structure between Indonesian-Malaysian and Philippine macaques. The pattern of divergence and polymorphism between M. fascicularis and M. mulatta shows a footprint of genetic exchange not only within their current hybrid zone but also across a wider range for more than 1 million years. However, genetic admixture may not be a random event in the genome. Whereas randomly selected genic and intergenic regions have the same evolutionary dynamics between the species, some cytochrome oxidase P450 (CYP) genes (major chemical metabolizing genes and potential target genes for local adaptation) have a significantly larger species divergence than other genes. By surveying CYP3A5 gene sequences of more than a hundred macaques, we identified three nonsynonymous single nucleotide polymorphisms that were highly differentiated between the macaques. The mosaic pattern of species divergence in the genomes may be a consequence of genetic differentiation under ecological adaptation and may be a salient feature in the genomes of nascent species under parapatry. PMID- 20579290 TI - Flotation preferentially selects saccate pollen during conifer pollination. AB - * Among many species of living conifers the presence of pollen with air bladders (saccate pollen) is strongly associated with downward-facing ovules and the production of pollination drops. This combination of features enables saccate pollen grains captured in the pollination drop to float upwards into the ovule. Despite the importance of this mechanism in understanding reproduction in living conifers and in extinct seed plants with similar morphologies, experiments designed to test its effectiveness have yielded equivocal results. * In vitro and in vivo pollination experiments using saccate and nonsaccate pollen were performed using modeled ovules and two Pinus species during their natural pollination period. * Buoyant saccate pollen readily floated through aqueous droplets, separating these grains from nonbuoyant pollen and spores. Ovules that received saccate pollen, nonsaccate pollen or a mixture of both all showed larger amounts and higher proportions of saccate pollen inside ovules after drop secretion. * These results demonstrate that flotation is an effective mechanism of pollen capture and transport in gymnosperms, and suggest that the prevalence of saccate grains and downward-facing ovules in the evolutionary history of seed plants is a result of the widespread use of this mechanism. PMID- 20579291 TI - Full disclosure. PMID- 20579293 TI - Smoking cessation in pregnancy: Health implications for mothers, infants and families. PMID- 20579295 TI - The nursing perspective. PMID- 20579296 TI - Issues for consideration. PMID- 20579297 TI - Assessing the teen parent family: the role for nurses. PMID- 20579298 TI - Advances in the early detection of ovarian cancer: How to hear the whispers early. PMID- 20579299 TI - Peer mentoring: When nurses share time and expertise, everyone wins. PMID- 20579300 TI - Educational programs: effective or not? PMID- 20579301 TI - Sleep is a vital sign: Why assessing sleep is an important part of women's health care. PMID- 20579304 TI - In praise of mentors. PMID- 20579305 TI - Prospective randomized trial of venous cardiac computed tomographic angiography for facilitation of cardiac resynchronization therapy. AB - BACKGROUND: Cardiovascular computed tomographic angiography (CTA) can visualize the coronary veins. We sought to assess the ability of CTA to facilitate resynchronization therapy (CRT) procedures using a prospective randomized single center pilot study. METHODS: Patients underwent CTA for characterization of cardiomyopathy prior to biventricular implantable cardiac-defibrillator implant. Randomization was performed with operator review of the CTA for coronary venous anatomy prior to CRT in one-half of the cases. Invasive coronary venous angiograms were used in all procedures. Analysis included procedure times and utilization of contrast, fluoroscopy, and guide catheters. RESULTS: Characteristics of the 26 patients enrolled were mean age 55 +/- 11 years, male 76.9%, ischemic etiology 35%, ejection fraction 25 +/- 3%, class III congestive heart failure 100%, and QRS duration 179 +/- 29 ms. Of patients enrolled, 22 had both CTA and procedure initiation. Three patients (two with CTA review and one without CTA review) had aborted procedures due to hemodynamic issues. Analysis of the 22 patients (nine with preprocedure CTA review and 13 without CTA review) demonstrated that preprocedure review of CTA coronary venous anatomy led to significantly decreased procedure times and utilization of contrast, fluoroscopy, and guide catheters. CONCLUSIONS: Preprocedure review of CTA coronary venous anatomy may lead to decreased procedural times and utilization of contrast, fluoroscopy, and guide catheters. These preliminary results will need to be evaluated in larger heart failure populations undergoing CRT. PMID- 20579306 TI - Young infants with atopic dermatitis can display sensitization to Cor a 9, an 11S legumin-like seed-storage protein from hazelnut (Corylus avellana). AB - Allergy to hazelnut (Corylus avellana) can be severe and occur at young age. Atopic dermatitis (AD) can involve sensitization to various foods. The objective is to investigate the pattern of hazelnut sensitization in infants with AD. Sera of 34 infants all under 1 year of age and suffering from AD were selected according to prior specific IgE results. Twenty-nine infants were sensitized to traditional food allergens, five were not. From the 29 infants with a sensitization to at least one food allergen, 20 demonstrated IgE reactivity to hazelnut. All sera were analyzed with the allergen microarray immunoassay (ImmunoCAP ISAC). Twelve (60%) of the children with IgE reactivity to hazelnut demonstrated sensitization to Cor a 9, the 11S legumin-like seed-storage protein from hazelnut. In these infants, no sensitization to Cor a 1, the homologue of the major birch pollen allergen Bet v 1 (Betula verrucosa), or the lipid transfer protein (Cor a 8) from hazelnut was demonstrable. Half of the children sensitized to Cor a 9 demonstrated IgE reactivity to its homologue in peanut (Arachis hypogaea; Ara h 3) from which five were also sensitized to Gly m 6 from soy (Glycine max). None of the infants with AD without IgE reactivity to hazelnut demonstrated sensitization to Cor a 1, 8, or 9. In conclusion, young infants with atopic dermatitis sensitized to hazelnut can already display IgE reactivity to Cor a 9, a potentially dangerous hazelnut component. The mechanism(s) of this early sensitization and its clinical significance remain elusive. PMID- 20579307 TI - Dendritic cell vaccination in human melanoma: relationships between clinical effects and vaccine parameters. AB - Eleven years have passed since the start of the first trial of dendritic cell (DC) vaccination for melanoma. A review of 54 trials was performed to evaluate the relationship between clinical effects and vaccine parameters. Significant differences were found between use of immature and mature DCs with regard to progressive disease (PD), between stage III and IV for clinical response, between use and non-use of adjuvants with regard to stable disease (SD) in treatment with tumor/tumor lysate-pulsed DCs, between positive and negative delayed-type hypersensitivity (DTH) for PD, and between increased and unchanged interferon (IFN)-gamma-secreting T cells for clinical response. These results are consistent with the partial efficacy of vaccination with mature DCs in early stage melanoma and the partial correlation of efficacy with positive DTH and increased IFN-gamma secreting T cells. DC vaccination alone had a limited clinical effect and a modified regimen is needed to enhance antigen-specific cytotoxic T cells and decrease immunosuppression. PMID- 20579309 TI - The origin of the non-recombining region of sex chromosomes in Carica and Vasconcellea. AB - Carica and Vasconcellea are two closely related sister genera in the family Caricaceae, and were once classified as two sections under Carica. Sex chromosomes have been found in papaya and originated approximately 2-3 million years ago. The objectives of this study were to determine whether sex chromosomes have evolved in Vasconcellea. Six X/Y gene pairs were cloned, sequenced and analyzed from three dioecious, one trioecious and one monoecious species of Vasconcellea. The isolation of distinctive X and Y alleles in dioecious and trioecious species of Vasconcellea demonstrated that sex chromosomes have evolved in this genus. Phylogenetic analyses indicated a monophyletic relationship between the X/Y alleles of Carica and those of Vasconcellea. Distinctive clusters of X/Y alleles were documented in V. parviflora and V. pulchra for all available gene sequences, and in V. goudatinana and V. cardinamarcensis for some X/Y alleles. The X and Y alleles within each species shared most single nucleotide polymorphism haplotypes that differed from other species. Limited evidence of gene conversion was documented among the X/Y alleles of some species, but was not sufficient to cause the evolutionary patterns reported herein. The Carica and Vasconcellea sex chromosomes may have originated from the same autosomes bearing the X allelic form that still exist in the monoecious species V. monoica, and have evolved independently after the speciation event that separated Carica from Vasconcellea. Within Vasconcellea, sex chromosomes have evolved at the species level, at least for some species. PMID- 20579312 TI - A mock terrorism application of the P300-based concealed information test. AB - Previous studies examining the P300-based concealed information test typically tested for mock crime or autobiographical details, but no studies have used this test in a counterterrorism scenario. Subjects in the present study covertly planned a mock terrorist attack on a major city. They were then given three separate blocks of concealed information testing, examining for knowledge of the location, method, and date of the planned terrorist attack, using the Complex Trial Protocol (Rosenfeld et al., 2008). With prior knowledge of the probe items, we detected 12/12 guilty subjects as having knowledge of the planned terrorist attack with no false positives among 12 innocent subjects. Additionally, we were able to identify 10/12 subjects and among them 20/30 crime-related details with no false positives using restricted a priori knowledge of the crime details, suggesting that the protocol could potentially identify future terrorist activity. PMID- 20579310 TI - Analysis of secondary growth in the Arabidopsis shoot reveals a positive role of jasmonate signalling in cambium formation. AB - After primary growth, most dicotyledonous plants undergo secondary growth. Secondary growth involves an increase in the diameter of shoots and roots through formation of secondary vascular tissue. A hallmark of secondary growth initiation in shoots of dicotyledonous plants is the initiation of meristematic activity between primary vascular bundles, i.e. in the interfascicular regions. This results in establishment of a cylindrical meristem, namely the vascular cambium. Surprisingly, despite its major implications for plant growth and the accumulation of biomass, the molecular regulation of secondary growth is only poorly understood. Here, we combine histological, molecular and genetic approaches to characterize interfascicular cambium initiation in the Arabidopsis thaliana inflorescence shoot. Using genome-wide transcriptional profiling, we show that stress-related and touch-inducible genes are up-regulated in stem regions where secondary growth takes place. Furthermore, we show that the products of COI1, MYC2, JAZ7 and the touch-inducible gene JAZ10, which are components of the JA signalling pathway, are cambium regulators. The positive effect of JA application on cambium activity confirmed a stimulatory role of JA in secondary growth, and suggests that JA signalling triggers cell divisions in this particular context. PMID- 20579311 TI - Unintentional covert motor activations predict behavioral effects: Multilevel modeling of trial-level electrophysiological motor activations. AB - The present experiment measured an EEG indicator of motor cortex activation, the lateralized readiness potential (LRP), while participants performed a speeded category classification task. The LRP data showed that visually masked words triggered covert motor activations. These prime-induced motor activations preceded motor activations by subsequent (to-be-classified) visible target words. Multilevel statistical analyses of trial-level effects, applied here for the first time with electrophysiological data, revealed that accuracy and latency of classifying target words was affected by both (a) covert motor activations caused by visually masked primes and (b) spontaneous fluctuations in covert motor activations. Spontaneous covert motor fluctuations were unobserved with standard subject-level (multi-trial) analyses of grand-averaged LRPs, highlighting the utility of multilevel modeling of trial-level effects. PMID- 20579313 TI - HLA-B*18:35, a new HLA-B*18 allele identified by sequence-based typing in a Brazilian volunteer bone marrow donor. AB - A novel human leukocyte antigen-B allele named B*18:35 was identified in a Brazilian volunteer bone marrow donor. PMID- 20579314 TI - The novel HLA-B*15:180 allele appears to be a recombinant B*08/B*15 allele. AB - Human leukocyte antigen B-*15:180 is a B*08/B*15 recombinant allele similar to B*15:29 with substitutions positions at 97, 292, 538, 539. PMID- 20579315 TI - Dfm1 forms distinct complexes with Cdc48 and the ER ubiquitin ligases and is required for ERAD. AB - Proteins imported into the endoplasmic reticulum (ER) are scanned for their folding status. Those that do not reach their native conformation are degraded via the ubiquitin-proteasome system. This process is called ER-associated degradation (ERAD). Der1 is known to be one of the components required for efficient degradation of soluble ERAD substrates like CPY(*) (mutated carboxypeptidase yscY). A homologue of Der1 exists, named Dfm1. No function of Dfm1 has been discovered, although a C-terminally hemagglutinin (HA)(3)-tagged Dfm1 protein has been shown to interact with the ERAD machinery. In our studies, we found Dfm1-HA(3) to be an ERAD substrate and therefore not suitable for functional studies of Dfm1 in ERAD. We found cellular, non-tagged Dfm1 to be a stable protein. We identified Dfm1 to be part of complexes which contain the ERAD L ligase Hrd1/Der3 and Der1 as well as the ERAD-C ligase Doa10. In addition, ERAD of Ste6(*)-HA(3) was strongly dependent on Dfm1. Interestingly, Dfm1 forms a complex with the AAA-ATPase Cdc48 in a strain lacking the Cdc48 membrane recruiting component Ubx2. This complex does not contain the ubiquitin ligases Hrd1/Der3 and Doa10. The existence of such a complex might point to an additional function of Dfm1 independent from ERAD. PMID- 20579316 TI - Downregulation of cytolytic activity of human effector cells by transgenic expression of human PD-ligand-1 on porcine target cells. AB - Cellular rejection is a relevant hurdle for successful pig-to-primate xenotransplantation. We have shown previously that the induction of a human anti pig T cell response (in vitro activation of CD4(+) T cells) can be suppressed by the overexpression of human negative costimulatory ligands (e.g. programmed death receptor ligand, PD-L1) on pig antigen presenting cells. Here, we asked whether PD-L1 mediated enhancement of negative signaling might also be efficient during the effector phase of human anti-pig cellular immune responses. The porcine B cell line L23 was transfected with human PD-L1, and clones were selected stably expressing PD-L1 with low, medium, or high density. Mock-transfected L23 cells were effectively lysed by human cytotoxic effector cells (IL-2 activated CD8(+) T cells and CD56(+) cells). The lytic potential of the effectors decreased with increasing levels of PD-L1 and was reduced by about 50% in L23-PD-L(high) targets. A proportion of activated CD8(+) effector cells underwent apoptosis when exposed to PD-L1 expressing L23 cells. These data suggest that the overexpression of PD-L1 on target cells may (a) trigger negative signals in effector cells that prevent the release of cytolytic molecules and/or (b) induce apoptosis in the attacking effector cells thereby protecting targets from destruction. PMID- 20579317 TI - Abstracts of the Joint 6th ELITA-ELTR (European Society for Organ Transplantation European Liver and Intestine Transplant Association) 5th NHBD International Meeting. London, United Kingdom. May 13-15, 2010. PMID- 20579318 TI - Differentiating Taenia eggs found in human stools: does Ziehl-Neelsen staining help? AB - OBJECTIVE: To determine whether Ziehl-Neelsen staining can differentiate Taenia solium from Taenia saginata eggs. METHODS: Tapeworm proglottids (33 specimens, 23 T. solium and 10 T. saginata) and eggs (31 specimens, 13 T. solium and 18 T. saginata) were stained. Four eggs from each sample were measured and average diameters were recorded. RESULTS: Taenia saginata eggs stained entirely magenta in seven of 13 cases. Taenia solium eggs stained entirely blue/purple in 4/18 cases and entirely magenta in one. Eggs of T. saginata were slightly larger and always ovoid, while T. solium eggs were smaller and mostly spheric. CONCLUSIONS: Ziehl-Neelsen staining can occasionally distinguish fully mature T. solium from T. saginata eggs, but this distinction is neither very sensitive nor completely specific. Differential staining suggests differences in embryophore components between species which become evident with egg maturation. In this small series, egg morphology (shape, maximal diameter) provided appropriate differentiation between T. solium and T. saginata eggs. PMID- 20579319 TI - Trypanosoma cruzi TcIII/Z3 genotype as agent of an outbreak of Chagas disease in the Brazilian Western Amazonia. AB - Chagas' disease is an emerging and neglected disease in the Brazilian Amazon region, where T. cruzi I predominates among the acute cases of the disease; and T. cruzi III/Z3, a population cluster from sylvatic areas of the Amazon basin, is rarely associated with human infections. On 23rd April 2007, the Foundation for Health Surveillance of the State of Amazonas, Brazil reported an outbreak of acute Chagas disease in the municipality of Coari on the Solimoes River banks. Fresh blood examination confirmed the infection in 25 patients. Parasite culture in LIT medium was successful for 18 isolates. Molecular characterization was performed by PCR of the non-transcribed spacer of the mini-exon and by sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene. The T. cruzi isolates were all from genotype Z3, and sequencing revealed that all isolates had equal COII sequences compatible with TcIII type, suggesting a single source of infection. To our knowledge, this is the first outbreak of acute cases caused uniquely by the genotype TcIII/Z3. Wild vectors harbouring TcIII stocks contribute to transmission when the triatomine species reaches human food chain or when humans invade the forest environment, where sylvatic cycle constitutes a reservoir of parasites that might be associated with specific epidemiological and clinical traits of the emergent Chagas disease in the Amazon. PMID- 20579320 TI - Acanthomatous ameloblastoma in dogs treated with intralesional bleomycin. AB - Acanthomatous ameloblastoma (AA) is a benign gingival tumour that often invades bone. This retrospective study evaluated the efficacy of intralesional (IL) bleomycin as a treatment for AA. Six dogs received weekly or bimonthly IL bleomycin injections (dose range, 10-20 U m(-2)). A seventh dog presented with advanced, nonresectable AA was treated palliatively. One to sixteen treatments were administered (median, 5). Six of the seven dogs had a complete response within 4 months from initial IL injection (median, 1.5 months), whereas the palliative case had approximately 25% decrease in tumour volume 14 days from initial injection. Local recurrence was not observed during the study period, with a median follow-up time of 842 days. Adverse effects were limited to wound formation with bone exposure (n = 4), mild tissue reactions (n = 3), local swelling (n = 2) and local infection (n = 1). The conclusions of this study show IL bleomycin is an effective treatment for canines with AA. PMID- 20579321 TI - Expression of the high mobility group A1 (HMGA1) and A2 (HMGA2) genes in canine lymphoma: analysis of 23 cases and comparison to control cases. AB - Overexpression of high mobility group A (HMGA) genes was described as a prognostic marker in different human malignancies, but its role in canine haematopoietic malignancies was unknown so far. The objective of this study was to analyse HMGA1 and HMGA2 gene expression in lymph nodes of canine lymphoma patients. The expression of HMGA1 and HMGA2 was analysed in lymph node samples of 23 dogs with lymphoma and three control dogs using relative quantitative real time RT-PCR. Relative quantity of HMGA1 was significantly higher in dogs with lymphoma compared with reference samples. HMGA2 expression did not differ between lymphoma and control dogs. With the exception of immunophenotype, comparison of disease parameters did not display any differences in HMGA1 and HMGA2 expression. The present findings indicate a role of HMGA genes in canine lymphoma. This study represents the basis for future veterinary and comparative studies dealing with their diagnostic, prognostic and therapeutic values. PMID- 20579323 TI - Phase II open-label study of single-agent hydroxyurea for treatment of mast cell tumours in dogs. AB - This prospective study evaluated the efficacy and safety of hydroxyurea (HU) in dogs with measurable mast cell tumours (MCTs). Dogs were treated with HU at 60 mg kg(-1)per os q24h for 14 days then 30 mg kg(-1) q24h thereafter or until MCT recurrence. Forty-six dogs were enrolled. The overall response rate was 28%. Two dogs had a complete response (CR) for 256 and 448 days, respectively. Eleven dogs had a partial response for a median duration of 46 days (range, 28-189 days). Grade 2 to 4 neutropenia occurred in eight dogs and grade 4 thrombocytopenia in two. Grade 3-4 anaemia occurred in seven dogs; overall, there was a significant decrease in haematocrit after treatment with HU. The median drop in haematocrit was 10%. This study demonstrated that HU has activity in the treatment of MCTs with mild anaemia being the primary adverse event. PMID- 20579322 TI - Interleukin-11 receptor alpha is expressed on canine osteosarcoma. AB - Osteosarcoma (OSA) is the most common bone tumour in humans and companion animals, and has a poor long-term prognosis. The identification of new markers and targeted therapies may help increase long-term survival of these patients. Previous studies have demonstrated that interleukin-11 receptor alpha (IL 11Ralpha) is expressed in human and murine OSA but not in normal bone. The current study demonstrated via western analysis, immunoflourescence and immunohistochemistry that IL-11Ralpha was expressed in primary canine OSA tissues as well as in a number of canine OSA cell lines, but not in normal canine bone. Cytotoxin-conjugated antibodies targeting IL-11Ralpha-mediated canine OSA cytotoxicity. Thus, canine OSA may be a valuable model for the evaluation of IL 11Ralpha directed therapies. PMID- 20579324 TI - Identification of hepatic stem/progenitor cells in canine hepatocellular and cholangiocellular carcinoma. AB - Hepatic progenitor cells (HPCs) are bipotential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic or cholangiocytic lineages. HPCs are present in both hepatocellular (HCC) and cholangiocellular carcinoma (CC) in humans; and a small percentage of HCC can originate from cancer stem cells. However, its distribution in canine liver tumour has not been studied. Herein, we searched for stem/progenitor cells in 13 HCC and 7 CC archived samples by immunohistochemical analysis. We found that both liver tumours presented a higher amount of K19-positive HPCs. Besides, 61.6% of HCC cases presented immature CD44-positive hepatocytes. Nevertheless, only two cases presented CD133-positive cells. As observed in humans, hepatic canine tumours presented activated HPCs, with important differentiation onto hepatocytes like cells and minimal role of cancer stem cells on HCC. These findings reiterate the applicability of canine model in the search for new therapies before application in humans. PMID- 20579325 TI - Cystosonographic measurements of canine bladder tumours. AB - The purpose of this study was to evaluate the variability of cystosonographic bladder tumor measurements with both operator and bladder volume changes. Ten dogs with bladder tumors were included. In each dog, three operators determined tumor dimensions for three different bladder volumes. Intraclass correlation coefficient was used to assess operator reliability. Response Evaluation Criteria in Solid Tumors (RECIST) and greater than or equal to 50% differences in tumor measurements were used as guidelines. Poor to fair correlations between operators were found for the different tumor dimensions (r(I) = 0.4 - 0.7). The percent differences in tumor dimensions with operator and bladder volume changes were significant enough to misclassify the tumors into the categories of partial response (PR) or progressive disease (PD). These results suggest that cystosonographic measurements of bladder tumors are affected by both changes in operator and bladder volume, and the discrepancies are significant enough to change response classification. PMID- 20579326 TI - High-mobility group B1 proteins in canine lymphoma: prognostic value of initial and sequential serum levels in treatment outcome following combination chemotherapy. AB - Elevated high-mobility group box 1 (HMGB1) levels have been demonstrated in different human neoplasias. Information on serum HMGB1 before and during chemotherapy is lacking, as is data pertaining to its prognostic significance. The aim of this study was to characterize serum HMGB1 level in dogs with lymphoma and to assess its influence on the outcome following chemotherapy. Serum HMGB1 concentrations were measured in 16 dogs with lymphoma before treatment (W1) and on weeks 2 (W2), 6 (W6) and 12 (W12) of treatment with chemotherapy. Initial serum HMGB1 levels were significantly higher than HMGB1concentrations in control dogs and the levels in W2, W6 and W12. HMGB1-W1 concentrations were lower in dogs achieving complete remission than that in the single dog with partial remission. The ratio W12/W6 exhibited significant influence on remission duration. In these dogs with lymphoma, serum HMGB1 was elevated in comparison with that in controls. Initial serum HMGB1 level and its modulation during treatment may possess prognostic value. PMID- 20579327 TI - A phase II study to evaluate the toxicity and efficacy of alternating CCNU and high-dose vinblastine and prednisone (CVP) for treatment of dogs with high-grade, metastatic or nonresectable mast cell tumours. AB - Safety and efficacy of a protocol of alternating 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea (CCNU; 70 mg m(-2)) and vinblastine (3.5 mg m(-2)), and prednisone (1 2 mg kg(-1); CVP) in dogs with mast cell tumours (MCT) were evaluated. A total of 17 dogs had nonresectable MCTs and 35 received CVP as adjunctive treatment to locoregional control of metastatic MCTs or grade III MCTs. Neutropenia with fever occurred in 8% of dogs after treatment with vinblastine and in 2% after treatment with CCNU. Persistent elevation of serum alanine transaminase, suggestive of hepatotoxicity, occurred in 9% of the dogs. Response rate in dogs with nonresectable MCTs was 65%; five achieved a complete response (median, 141 days) and six achieved a partial response (median, 66 days). Overall median progression free survival (PFS) time in dogs treated in the adjuvant setting was 489 days. Dogs with grade III MCTs had shorter PFS compared with dogs with metastatic grade II MCTs (190 days versus 954 days; P < 0.001). Phase III studies are needed to provide reliable information about the comparative efficacy of this protocol. PMID- 20579330 TI - Guidelines for the use of RFID technology in transfusion medicine. PMID- 20579331 TI - Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection. AB - BACKGROUND: Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk. OBJECTIVE: Our study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females. METHODS: This study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22) and one region (exon 9) of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed. RESULTS: Mutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80 (67%) out of total 120, were mutation carriers. CONCLUSIONS: BRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations were found in individuals with and without family history. PMID- 20579332 TI - Recruiting participants for interventions to prevent the onset of depressive disorders: possible ways to increase participation rates. AB - BACKGROUND: Although indicated prevention of depression is available for about 80% of the Dutch population at little or no cost, only a small proportion of those with subthreshold depression make use of these services. METHODS: A narrative review is conducted of the Dutch preventive services in mental health care, also addressing the problem of low participation rates. We describe possible causes of these low participation rates, which may be related to the participants themselves, the service system, and the communication to the public, and we put forward possible solutions to this problem. RESULTS: There are three main groups of reasons why the participation rates are low: reasons within the participants (e.g., not considering themselves as being at risk; thinking the interventions are not effective; or being unwilling to participate because of the stigma associated with depression); reasons within the health care system; and reasons associated with the communication about the preventive services. Possible solutions to increasing the participation rate include organizing mass media campaigns, developing internet-based preventive interventions, adapting preventive interventions to the needs of specific subpopulations, positioning the services in primary care, integrating the interventions in community-wide interventions, and systematically screening high-risk groups for potential participants. DISCUSSION: Prevention could play an important role in public mental health in reducing the enormous burden of depression. However, before this can be realized more research is needed to explore why participation rates are low and how these rates can be improved. PMID- 20579333 TI - Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. AB - OBJECTIVES: Squamous cell carcinoma (SCC) is by far the most common malignant neoplasm of the oral cavity. A number of etiologic factors have been implicated in its development. During the past few decades, a particular focus has been placed on the investigation of valid biomarkers predictive of cancer behavior and cervical lymph node metastasis in head and neck Squamous cell carcinoma (HNSCC).The present study was designed to investigate the expression of epidermal growth factor in these tumors in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. MATERIALS AND METHODS: Immunohistochemical (IHC) evaluation of epidermal growth factor receptor (EGFR) expression in 40 retrospective OSCC specimens and its correlation with proliferating cell nuclear antigen (PCNA), antiapoptotic antibody (P53), vascular endothelial growth factor (VEGF), and D2-40 monoclonal antibodies (Mab), in relation to the clinicopathological parameters. RESULTS: Data revealed positive EGFR immunoreactivity in 35(87.5%) cases. There was a statistically significant correlation regarding EGFR extent score with respect to intratumoral lymphatic vessel density (ILVD) (r = 0.35) as well as EGFR intensity score with respect to ILVD and peritumoral lymphatic vessel density (PLVD) (r = 0.33, r = 0.36 respectively). EGFR expression was not correlated with the clinicopathological parameters. CONCLUSIONS: EGFR is expressed by most of the cases. EGFR correlation with D2- 40 positive lymphatic vessels suggests a higher tendency of OSCC for lymphatic dissemination. Lack of correlation among the studied markers suggests their independent effect on tumor behavior. PMID- 20579334 TI - Metamotifs--a generative model for building families of nucleotide position weight matrices. AB - BACKGROUND: Development of high-throughput methods for measuring DNA interactions of transcription factors together with computational advances in short motif inference algorithms is expanding our understanding of transcription factor binding site motifs. The consequential growth of sequence motif data sets makes it important to systematically group and categorise regulatory motifs. It has been shown that there are familial tendencies in DNA sequence motifs that are predictive of the family of factors that binds them. Further development of methods that detect and describe familial motif trends has the potential to help in measuring the similarity of novel computational motif predictions to previously known data and sensitively detecting regulatory motifs similar to previously known ones from novel sequence. RESULTS: We propose a probabilistic model for position weight matrix (PWM) sequence motif families. The model, which we call the 'metamotif' describes recurring familial patterns in a set of motifs. The metamotif framework models variation within a family of sequence motifs. It allows for simultaneous estimation of a series of independent metamotifs from input position weight matrix (PWM) motif data and does not assume that all input motif columns contribute to a familial pattern. We describe an algorithm for inferring metamotifs from weight matrix data. We then demonstrate the use of the model in two practical tasks: in the Bayesian NestedMICA model inference algorithm as a PWM prior to enhance motif inference sensitivity, and in a motif classification task where motifs are labelled according to their interacting DNA binding domain. CONCLUSIONS: We show that metamotifs can be used as PWM priors in the NestedMICA motif inference algorithm to dramatically increase the sensitivity to infer motifs. Metamotifs were also successfully applied to a motif classification problem where sequence motif features were used to predict the family of protein DNA binding domains that would interact with it. The metamotif based classifier is shown to compare favourably to previous related methods. The metamotif has great potential for further use in machine learning tasks related to especially de novo computational sequence motif inference. The metamotif methods presented have been incorporated into the NestedMICA suite. PMID- 20579335 TI - Brief psychological therapies for anxiety and depression in primary care: meta analysis and meta-regression. AB - BACKGROUND: Psychological therapies provided in primary care are usually briefer than in secondary care. There has been no recent comprehensive review comparing their effectiveness for common mental health problems. We aimed to compare the effectiveness of different types of brief psychological therapy administered within primary care across and between anxiety, depressive and mixed disorders. METHODS: Meta-analysis and meta-regression of randomized controlled trials of brief psychological therapies of adult patients with anxiety, depression or mixed common mental health problems treated in primary care compared to primary care treatment as usual. RESULTS: Thirty-four studies, involving 3962 patients, were included. Most were of brief cognitive behaviour therapy (CBT; n = 13), counselling (n = 8) or problem solving therapy (PST; n = 12). There was differential effectiveness between studies of CBT, with studies of CBT for anxiety disorders having a pooled effect size [d -1.06, 95% confidence interval (CI) -1.31 to -0.80] greater than that of studies of CBT for depression (d -0.33, 95% CI -0.60 to -0.06) or studies of CBT for mixed anxiety and depression (d 0.26, 95% CI -0.44 to -0.08). Counselling for depression and mixed anxiety and depression (d -0.32, 95% CI -0.52 to -0.11) and problem solving therapy (PST) for depression and mixed anxiety and depression (d -0.21, 95% CI -0.37 to -0.05) were also effective. Controlling for diagnosis, meta-regression found no difference between CBT, counselling and PST. CONCLUSIONS: Brief CBT, counselling and PST are all effective treatments in primary care, but effect sizes are low compared to longer length treatments. The exception is brief CBT for anxiety, which has comparable effect sizes. PMID- 20579336 TI - Bridging the gaps in the Health Management Information System in the context of a changing health sector. AB - BACKGROUND: The Health Management Information System (HMIS) is crucial for evidence-based policy-making, informed decision-making during planning, implementation and evaluation of health programs; and for appropriate use of resources at all levels of the health system. This study explored the gaps and factors influencing HMIS in the context of a changing health sector in Tanzania. METHODS: A cross sectional descriptive study was conducted in 11 heath facilities in Kilombero district between January and February 2008. A semi-structured questionnaire was used to interview 43 health workers on their knowledge, attitude, practice and factors for change on HMIS and HMIS booklets from these facilities were reviewed for completeness. RESULTS: Of all respondents, 81% had never been trained on HMIS, 65% did not properly define this system, 54% didn't know who is supposed to use the information collected and 42% did not use the collected data for planning, budgeting and evaluation of services provision. Although the attitude towards the system was positive among 91%, the reviewed HMIS booklets were never completed in 25% - 55% of the facilities. There were no significant differences in knowledge, attitude and practice on HMIS between clinicians and nurses. The most common type of HMIS booklets which were never filled were those for deliveries (55%). The gaps in the current HMIS were linked to lack of training, inactive supervision, staff workload pressure and the lengthy and laborious nature of the system. CONCLUSIONS: This research has revealed a state of poor health data collection, lack of informed decision-making at the facility level and the factors for change in the country's HMIS. It suggests need for new innovations including incorporation of HMIS in the ongoing reviews of the curricula for all cadres of health care providers, development of more user-friendly system and use of evidence-based John Kotter's eight-step process for implementing successful changes in this system. PMID- 20579337 TI - Characterization of SQUAMOSA-like genes in Gerbera hybrida, including one involved in reproductive transition. AB - BACKGROUND: The flowering process in plants proceeds through the induction of an inflorescence meristem triggered by several pathways. Many of the genes associated with both the flowering process and floral architecture encode transcription factors of the MADS domain family. Gerbera, a member of the sunflower family, Asteraceae, bears compressed inflorescence heads (capitula) with three different flower types characterized by differences in both sexuality and floral symmetry. To understand how such a complex inflorescence structure is achieved at the molecular level, we have characterized the array of Gerbera MADS box genes. The high number of SQUAMOSA-like genes in Gerbera compared to other model species raised the question as to whether they may relate to Gerbera's complex inflorescence structure and whether or not a homeotic A function is present. RESULTS: In this paper we describe six Gerbera genes related to the SQUAMOSA/APETALA1/FRUITFULL genes of snapdragon and Arabidopsis. Based on phylogenetic analysis of the entire gene lineage, our data indicates that GSQUA1 and GSQUA3 are members of the SQUA/AP1 clade, while GSQUA2, GSQUA4, GSQUA5 and GSQUA6 are co-orthologs of the Arabidopsis FUL gene. GSQUA1/GSQUA3 and GSQUA4/GSQUA5/GSQUA6, respectively, represent several gene duplication events unknown in the model systems that may be specific to either Gerbera or Asteraceae. GSQUA genes showed specific expression profiles. GSQUA1, GSQUA2, and GSQUA5 were inflorescence abundant, while GSQUA3, GSQUA4, and GSQUA6 expression was also detected in vegetative organs. Overexpression of GSQUA2 in Gerbera led to accelerated flowering, dwarfism and vegetative abnormalities, all new and specific phenomena observed in transgenic Gerbera plants with modified MADS box gene expression. CONCLUSIONS: Based on expression patterns, none of the Gerbera SQUA-like genes are likely to control flower organ identity in the sense of the floral A function. However, our data shows that the FUL-like gene GSQUA2 plays a vital role in meristem transition. The roles of other GSQUA-genes in Gerbera floral development are intriguing, but require still further study. PMID- 20579338 TI - Large scale interaction analysis predicts that the Gerbera hybrida floral E function is provided both by general and specialized proteins. AB - BACKGROUND: The ornamental plant Gerbera hybrida bears complex inflorescences with morphologically distinct floral morphs that are specific to the sunflower family Asteraceae. We have previously characterized several MADS box genes that regulate floral development in Gerbera. To study further their behavior in higher order complex formation according to the quartet model, we performed yeast two- and three-hybrid analysis with fourteen Gerbera MADS domain proteins to analyze their protein-protein interaction potential. RESULTS: The exhaustive pairwise interaction analysis showed significant differences in the interaction capacity of different Gerbera MADS domain proteins compared to other model plants. Of particular interest in these assays was the behavior of SEP-like proteins, known as GRCDs in Gerbera. The previously described GRCD1 and GRCD2 proteins, which are specific regulators involved in stamen and carpel development, respectively, showed very limited pairwise interactions, whereas the related GRCD4 and GRCD5 factors displayed hub-like positions in the interaction map. We propose GRCD4 and GRCD5 to provide a redundant and general E function in Gerbera, comparable to the SEP proteins in Arabidopsis. Based on the pairwise interaction data, combinations of MADS domain proteins were further subjected to yeast three-hybrid assays. Gerbera B function proteins showed active behavior in ternary complexes. All Gerbera SEP-like proteins with the exception of GRCD1 were excellent partners for B function proteins, further implicating the unique role of GRCD1 as a whorl- and flower-type specific C function partner. CONCLUSIONS: Gerbera MADS domain proteins exhibit both conserved and derived behavior in higher order protein complex formation. This protein-protein interaction data can be used to classify and compare Gerbera MADS domain proteins to those of Arabidopsis and Petunia. Combined with our reverse genetic studies of Gerbera, these results reinforce the roles of different genes in the floral development of Gerbera. Building up the elaborate capitulum of Gerbera calls for modifications and added complexity in MADS domain protein behavior compared to the more simple flowers of, e.g., Arabidopsis. PMID- 20579339 TI - Superior vena cava syndrome in a patient with previous cardiac surgery: what else should we suspect? AB - BACKGROUND: Although mediastinal tumors compressing or invading the superior vena cava represent the major causes of the superior vena cava syndrome, benign processes may also be involved in the pathogenesis of this medical emergency. One of the rarest benign causes is a pseudoaneurysm developing in patients previously having heart surgery. CASE REPORT: We present the case of a large pseudoaneurysm of the ascending aorta, five years after primary surgery, with a significant compression of the right mediastinal venous system causing superior vena cava syndrome, detected at chest CT angiography. Perioperative findings showed two rush out points both coming from the distal aortic suture line which was performed five years ago. The patient underwent reoperation under circulatory arrest facilitating safe exploration and repair of the distal anastomotic leaks CONCLUSION: Enhanced chest CT should be always undertaken in all patients with superior vena cava syndrome, especially in those previously having cardiac or aortic surgery to correctly evaluate the presence of a pseudoaneurysm. Mass effect to the superior vena cava makes necessary an open surgical treatment of the pseudoaneurysm so as to concurrently resolve the right mediastinal venous system's compression. Surgery should be performed in terms of safe approach to avoid exsanguination and cerebral malperfusion. PMID- 20579340 TI - Effects of enzyme feeding strategy on ethanol yield in fed-batch simultaneous saccharification and fermentation of spruce at high dry matter. AB - BACKGROUND: To make lignocellulosic fuel ethanol economically competitive with fossil fuels, it is necessary to reduce the production cost. One way to achieve this is by increasing the substrate concentration in the production process, and thus reduce the energy demand in the final distillation of the fermentation broth. However, increased substrate concentration in simultaneous saccharification and fermentation (SSF) processes has been shown to result in reduced ethanol yields and severe stirring problems. Because the SSF medium is being continuously hydrolyzed, running the process in fed-batch mode could potentially reduce the stirring problems and lead to increased ethanol yields in high-solids SSF. Different enzyme feeding strategies, with the enzymes either present in the reactor from start-up or fed into the reactor together with the substrate, have been studied, along with the influence of the enzyme feeding strategy on the final ethanol yield and productivity. RESULTS: In the present study, SSF was run successfully with 10% and 14% water-insoluble solids (WIS) in batch and fed-batch mode. The mixing of the material in the reactor was significantly better in fed-batch than batch mode, and similarly high or higher ethanol yields were achieved in fed-batch mode compared with batch SSF in some cases. No general trend in the dependence of ethanol yield on enzyme feeding strategy was found. CONCLUSIONS: The optimum enzyme feeding strategy appears to depend on the conditions during SSF, such as the WIS concentration and the concentration of inhibitory compounds in the SSF medium. PMID- 20579341 TI - Costing the scaling-up of human resources for health: lessons from Mozambique and Guinea Bissau. AB - INTRODUCTION: In the context of the current human resources for health (HRH) crisis, the need for comprehensive Human Resources Development Plans (HRDP) is acute, especially in resource-scarce sub-Saharan African countries. However, the financial implications of such plans rarely receive due consideration, despite the availability of much advice and examples in the literature on how to conduct HRDP costing. Global initiatives have also been launched recently to standardise costing methodologies and respective tools. METHODS: This paper reports on two separate experiences of HRDP costing in Mozambique and Guinea Bissau, with the objective to provide an insight into the practice of costing exercises in information-poor settings, as well as to contribute to the existing debate on HRH costing methodologies. The study adopts a case-study approach to analyse the methodologies developed in the two countries, their contexts, policy processes and actors involved. RESULTS: From the analysis of the two cases, it emerged that the costing exercises represented an important driver of the HRDP elaboration, which lent credibility to the process, and provided a financial framework within which HRH policies could be discussed. In both cases, bottom-up and country specific methods were designed to overcome the countries' lack of cost and financing data, as well as to interpret their financial systems. Such an approach also allowed the costing exercises to feed directly into the national planning and budgeting process. CONCLUSIONS: The authors conclude that bottom-up and country-specific costing methodologies have the potential to serve adequately the multi-faceted purpose of the exercise. It is recognised that standardised tools and methodologies may help reduce local governments' dependency on foreign expertise to conduct the HRDP costing and facilitate regional and international comparisons. However, adopting pre-defined and insufficiently flexible tools may undermine the credibility of the costing exercise, and reduce the space for policy negotiation opportunities within the HRDP elaboration process. PMID- 20579342 TI - Identification of proteins related to the stress response in Enterococcus faecalis V583 caused by bovine bile. AB - BACKGROUND: Enterococcus faecalis is an opportunistic pathogen and one of the most important causes of hospital infections. Bile acids are a major stress factor bacteria have to cope with in order to colonize and survive in the gastro intestinal tract. The aim of this study was to investigate the effects of bile acids on the intracellular proteome of E. faecalis V583. RESULTS: The proteomes of cells challenged with 1% bile were analyzed after 20 - 120 minutes exposure, using 2D gel electrophoresis and mass spectrometry. Among the approximately 500 observed proteins, 53 unique proteins were found to be regulated in response to bile and were identified with mass spectrometry. The identified proteins belonged to nine different functional classes, including fatty acid- and phospholipid biosynthesis, energy metabolism, and transport and binding. Proteins involved in fatty acid and phospholipid biosynthesis pathways were clearly overrepresented among the identified proteins and all were down-regulated upon exposure to bile. The proteome data correlated reasonably well with data from previous transcriptome experiments done under the same conditions, but several differences were observed. CONCLUSION: The results provide an overview of potentially important proteins that E. faecalis V583 needs to regulate in order to survive and adapt to a bile-rich environment, among which are several proteins involved in fatty acid and phospholipid biosynthesis pathways. In addition, this study reveals several hypothetical proteins, which are both abundant and clearly regulated and thus stand out as targets for future studies on bile stress. PMID- 20579343 TI - Outbreak of acute hemorrhagic conjunctivitis in Yunnan, People's Republic of China, 2007. AB - An outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Yunnan Province, China between August and September in 2007. A total of 3,597 cases were officially reported and the incidence rate reached 1390.94/100,000. Descriptive epidemiological analysis of the outbreak was conducted using the data from National Disease Supervision Information Management System (NDSIMS). To determine the causative agent for this outbreak and to analyze their genetic features, 30 conjunctival swabs and 19 paired serum specimens of acute and convalescent phase were collected from 30 patients with AHC, and viral isolation, molecular typing, antibody assay and phylogenetic analysis were performed. 11 virus strains were isolated from 30 conjunctival swabs. Amplification and sequencing of the VP4 region of these strains identified that coxsackievirus A24 variant (CA24v) could be the causative agent of the AHC outbreak and this was further confirmed by subsequent virus neutralizing antibody test on 19 paired serum specimens. Phylogenetic analysis based on the 3C regions showed that the Yunnan CA24v strains belonged to Group 3 and clustered with the strains isolated from worldwide AHC outbreaks after 2002. Phylogenetic analysis based on the partial VP1 revealed that the Yunnan strains differed from the strains isolated from AHC outbreak in Guangdong of China in 2007 with 2.8 - 3.0% nucleotide divergence, suggesting that two different lineages of CA24v caused the independent AHC outbreaks in Yunnan and Guangdong, respectively. PMID- 20579345 TI - Probiotic therapy - recruiting old friends to fight new foes. AB - Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative. PMID- 20579344 TI - Australia's national bowel cancer screening program: does it work for indigenous Australians? AB - BACKGROUND: Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP) using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population.This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups. METHODS: A search was undertaken of peer reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions. RESULTS: The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening. CONCLUSIONS: Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating the already widening disparities in cancer outcomes that exist among Indigenous Australians. Modifications to the program are recommended to facilitate access and participation by Indigenous and other minority populations. Further research is also needed to understand the needs and social and cultural sensitivities of these groups around cancer screening and inform alternative approaches to bowel cancer screening. PMID- 20579347 TI - The impact of Highly Active Antiretroviral Therapy (HAART) on the clinical features of HIV - related oral lesions in Nigeria. AB - BACKGROUND: This study aimed to determine the therapeutic effects of highly active anti-retroviral therapy (HAART) on the clinical presentations of HIV related oral lesions (HIV-ROLs) in an adult Nigerian population. METHODS: A 5 month prospective study on HAART naive HIV positive adults recruited into the HAART program of an AIDS referral centre. HIV-ROLs were diagnosed clinically by the EEC Clearinghouse on oral problems related to HIV infection. Baseline clinical features of HIV-ROLs was documented by clinical photographs using SONY(R) 5.2 M Cybershot digital camera. Post HAART monthly review was conducted using clinical photographs. RESULTS: A total of 142 patients were seen. Age range was 19 - 75 years. Mean age was 35.6 +/- 10.5 (SD). Eighty (56.3%) were females. Prevalence of HIV-ROLs was 43.7%. Oral candidiasis (22.4%) was the most prevalent HIV-ROL. 114 (83.2%) patients had clinical AIDS at presentation (CDC 1993). 89.4% were placed on Tenofovir/Emtricitabine +;Nevirapine, 9.9% on Tenofovir/Emtricitabine + Efavirenz. There was strong decline in the clinical features of oral candidiasis from a month of commencing HAART. Oral hairy leukoplakia was slow in responding to HAART. Parotid gland enlargement, melanotic hyperpigmentation and Kaposi's sarcoma were more persistent and had slower response to HAART. There was no clinical change noticed in linear gingival erythema. CONCLUSION: HAART has different clinical effects on HIV related oral lesions depending on the size, duration of treatment and etiology of the lesions. HIV-ROLs of fungal origin have the fastest response to HAART. These lesions alongside immunologic parameters can be used as indicators of success or failure of antiretroviral therapy. PMID- 20579346 TI - Consistency and precision of cancer reporting in a multiwave national panel survey. AB - BACKGROUND: Many epidemiological studies rely on self-reported information, the accuracy of which is critical for unbiased estimates of population health. Previously, accuracy has been analyzed by comparing self-reports to other sources, such as cancer registries. Cancer is believed to be a well-reported condition. This paper uses novel panel data to test the consistency of cancer reports for respondents with repeated self-reports. METHODS: Data come from 978 adults who reported having been diagnosed with cancer in at least one of four waves of the Panel Study of Income Dynamics, 1999-2005. Consistency of cancer occurrence reports and precision of timing of onset were studied as a function of individual and cancer-related characteristics using logistic and ordered logistic models. RESULTS: Almost 30% of respondents gave inconsistent cancer reports, meaning they said they never had cancer after having said they did have cancer in a previous interview; 50% reported the year of diagnosis with a discrepancy of two or more years. More recent cancers were reported with a higher consistency and timing precision; cervical cancer was reported more inaccurately than other cancer types. Demographic and socio-economic factors were only weak predictors of reporting quality. CONCLUSIONS: Results suggest that retrospective reports of cancer contain significant measurement error. The errors, however, are fairly random across different social groups, meaning that the results based on the data are not systematically biased by socio-economic factors. Even for health events as salient as cancer, researchers should exercise caution about the presumed accuracy of self-reports, especially if the timing of diagnosis is an important covariate. PMID- 20579348 TI - Factors associated with mosquito pool positivity and the characterization of the West Nile viruses found within Louisiana during 2007. AB - BACKGROUND: West Nile virus (WNV) is an arbovirus of public health importance in the genus Flavivirus, a group of positive sense RNA viruses. The NS3 gene has a high level of substitutions and is phylogenetically informative. Likewise, substitutions in the envelope region have been postulated to enable viruses to subvert immune responses. Analysis of these genes among isolates from positive mosquitoes collected in Louisiana illustrates the variation present in the regions and provides improved insight to a phylogenetic model. Employing a GIS eco-regionalization method, we hypothesized that WNV pool positivity was correlated with regional environmental characteristics. Further, we postulated that the phylogenetic delineations would be associated with variations in regional environmental conditions. RESULTS: Type of regional land cover was a significant effect (p < 0.0001) in the positive pool prediction, indicating that there is an ecological component driving WNV activity. Additionally, month of collection was significant (p < 0.0001); and thus there is a temporal component that contributes to the probability of getting a positive mosquito pool. All virus isolates are of the WNV 2002 lineage. There appears to be some diversity within both forested and wetland areas; and the possibility of a distinct clade in the wetland samples. CONCLUSIONS: The phylogenetic analysis shows that there has been no reversion in Louisiana from the 2002 lineage which replaced the originally introduced strain. Our pool positivity model serves as a basis for future testing, and could direct mosquito control and surveillance efforts. Understanding how land cover and regional ecology effects mosquito pool positivity will greatly help focus mosquito abatement efforts. This would especially help in areas where abatement programs are limited due to either funding or man power. Moreover, understanding how regional environments drive phylogenetic variation will lead to a greater understanding of the interactions between ecology and disease prevalence. PMID- 20579349 TI - Metals detected by ICP/MS in wound tissue of war injuries without fragments in Gaza. AB - BACKGROUND: The amount and identity of metals incorporated into "weapons without fragments" remain undisclosed to health personnel. This poses a long-term risk of assumption and contributes to additional hazards for victims because of increased difficulties with clinical management. We assessed if there was evidence that metals are embedded in "wounds without fragments" of victims of the Israeli military operations in Gaza in 2006 and 2009. METHODS: Biopsies of "wounds without fragments" from clinically classified injuries, amputation (A), charred (C), burns (B), multiple piercing wounds by White Phosphorus (WP) (M), were analyzed by ICP/MS for content in 32 metals. RESULTS: Toxic and carcinogenic metals were detected in folds over control tissues in wound tissues from all injuries: in A and C wounds (Al, Ti, Cu, Sr, Ba, Co, Hg, V, Cs and Sn), in M wounds (Al, Ti, Cu, Sr, Ba, Co and Hg) and in B wounds (Co, Hg, Cs, and Sn); Pb and U in wounds of all classes; B, As, Mn, Rb, Cd, Cr, Zn in wounds of all classes, but M; Ni was in wounds of class A. Kind and amounts of metals correlate with clinical classification of injuries, exposing a specific metal signature, similar for 2006 and 2009 samples. CONCLUSIONS: The presence of toxic and carcinogenic metals in wound tissue is indicative of the presence in weapon inducing the injury. Metal contamination of wounds carries unknown long term risks for survivors, and can imply effects on populations from environmental contamination. We discuss remediation strategies, and believe that these data suggest the need for epidemiological and environmental surveys. PMID- 20579350 TI - Readiness of the Belgian network of sentinel general practitioners to deliver electronic health record data for surveillance purposes: results of survey study. AB - BACKGROUND: In order to proceed from a paper based registration to a surveillance system that is based on extraction of electronic health records (EHR), knowledge is needed on the number and representativeness of sentinel GPs using a government certified EHR system and the quality of EHR data for research, expressed in the compliance rate with three criteria: recording of home visits, use of prescription module and diagnostic subject headings. METHODS: Data were collected by annual postal surveys between 2005 and 2009 among all sentinel GPs. We tested relations between four key GP characteristics (age, gender, language community, practice organisation) and use of a certified EHR system by multivariable logistic regression. The relation between EHR software package, GP characteristics and compliance with three quality criteria was equally measured by multivariable logistic regression. RESULTS: A response rate of 99% was obtained. Of 221 sentinel GPs, 55% participated in the surveillance without interruption from 2005 onwards, i.e. all five years, and 78% were participants in 2009. Sixteen certified EHR systems were used among 91% of the Dutch and 63% of the French speaking sentinel GPs. The EHR software package was strongly related to the community and only one EHR system was used by a comparable number of sentinel GPs in both communities. Overall, the prescription module was always used and home visits were usually recorded. Uniform subject headings were only sometimes used and the compliance with this quality criterion was almost exclusively related to the EHR software package in use. CONCLUSIONS: The challenge is to progress towards a sentinel network of GPs delivering care-based data that are (partly) extracted from well performing EHR systems and still representative for Belgian general practice. PMID- 20579351 TI - Analysis of pronuclear zygote configurations in 459 clinical pregnancies obtained with assisted reproductive technique procedures. AB - BACKGROUND: Embryos selection is crucial to maintain high performance in terms of pregnancy rate, reducing the risk of multiple pregnancy during IVF. Pronuclear and nucleolar characteristics have been proposed as an indicator of embryo development and chromosomal complement in humans, providing information about embryo viability. METHODS: To correlate the zygote-score with the maternal age and the outcome of pregnancy, we analyzed the pronuclear and nucleolar morphology, the polar body alignment and the zygote configuration in 459 clinical pregnancies obtained by IVF and ICSI in our public clinic in Reggio Emilia, Italy. We derived odds ratios (OR) and Corenfield's 95% confidence intervals (CI). Continuous variables were compared with Student's t-test; P lower than .05 was considered statistically significant. RESULTS: We observed a significant increase of "A" pronuclear morphology configuration in 38-41 years old patients in comparison to that lower than or equal to 32 years old and a significant decrease of "B" configuration in 38-41 years old patients in comparison to that lower than or equal to 32 and in comparison to that of 33-37 years old. Related to maternal age we found no significant differences in P1 and in P2 configuration. We found no correlation between zygote-score, embryo cleavage and embryo quality. CONCLUSIONS: Our results confirm the limited clinical significance of zygote-score suggesting that it can not be associated with maternal age, embryo cleavage and embryo quality. The evaluation of embryo quality based on morphological parameters is probably more predictive than zygote score. PMID- 20579352 TI - Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility. AB - BACKGROUND: Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors) or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated. METHODS: The association of polymorphic variants of GRIA1 GRIA4 genes which encode for the four subunits (GluR1-GluR4) of the alpha-amino-3 hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor for glutamate was tested in migraineurs with and without aura (MA and MO) and healthy controls. RESULTS: Two variants in the regulative regions of GRIA1 (rs2195450) and GRIA3 (rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in GRIA1 gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of GRIA1 and GRIA3 genes in different conditions. CONCLUSIONS: This study represents the first genetic evidence of a link between glutamate receptors and migraine. PMID- 20579353 TI - Prediction and analysis of near-road concentrations using a reduced-form emission/dispersion model. AB - BACKGROUND: Near-road exposures of traffic-related air pollutants have been receiving increased attention due to evidence linking emissions from high-traffic roadways to adverse health outcomes. To date, most epidemiological and risk analyses have utilized simple but crude exposure indicators, most typically proximity measures, such as the distance between freeways and residences, to represent air quality impacts from traffic. This paper derives and analyzes a simplified microscale simulation model designed to predict short- (hourly) to long-term (annual average) pollutant concentrations near roads. Sensitivity analyses and case studies are used to highlight issues in predicting near-road exposures. METHODS: Process-based simulation models using a computationally efficient reduced-form response surface structure and a minimum number of inputs integrate the major determinants of air pollution exposures: traffic volume and vehicle emissions, meteorology, and receptor location. We identify the most influential variables and then derive a set of multiplicative submodels that match predictions from "parent" models MOBILE6.2 and CALINE4. The assembled model is applied to two case studies in the Detroit, Michigan area. The first predicts carbon monoxide (CO) concentrations at a monitoring site near a freeway. The second predicts CO and PM2.5 concentrations in a dense receptor grid over a 1 km2 area around the intersection of two major roads. We analyze the spatial and temporal patterns of pollutant concentration predictions. RESULTS: Predicted CO concentrations showed reasonable agreement with annual average and 24-hour measurements, e.g., 59% of the 24-hr predictions were within a factor of two of observations in the warmer months when CO emissions are more consistent. The highest concentrations of both CO and PM(2.5) were predicted to occur near intersections and downwind of major roads during periods of unfavorable meteorology (e.g., low wind speeds) and high emissions (e.g., weekday rush hour). The spatial and temporal variation among predicted concentrations was significant, and resulted in unusual distributional and correlation characteristics, including strong negative correlation for receptors on opposite sides of a road and the highest short-term concentrations on the "upwind" side of the road. CONCLUSIONS: The case study findings can likely be generalized to many other locations, and they have important implications for epidemiological and other studies. The reduced-form model is intended for exposure assessment, risk assessment, epidemiological, geographical information systems, and other applications. PMID- 20579354 TI - Adenyl cyclases and cAMP in plant signaling - past and present. AB - In lower eukaryotes and animals 3'-5'-cyclic adenosine monophosphate (cAMP) and adenyl cyclases (ACs), enzymes that catalyse the formation of cAMP from ATP, have long been established as key components and second messengers in many signaling pathways. In contrast, in plants, both the presence and biological role of cAMP have been a matter of ongoing debate and some controversy. Here we shall focus firstly on the discovery of cellular cAMP in plants and evidence for a role of this second messenger in plant signal transduction. Secondly, we shall review current evidence of plant ACs, analyse aspects of their domain organisations and the biological roles of candidate molecules. In addition, we shall assess different approaches based on search motifs consisting of functionally assigned amino acids in the catalytic centre of annotated and/or experimentally tested nucleotide cyclases that can contribute to the identification of novel candidate molecules with AC activity such as F-box and TIR proteins. PMID- 20579355 TI - Delta opioid receptor on equine sperm cells: subcellular localization and involvement in sperm motility analyzed by computer assisted sperm analyzer (CASA). AB - BACKGROUND: Opioid receptors and endogenous opioid peptides act not only in the control of nociceptive pathways, indeed several reports demonstrate the effects of opiates on sperm cell motility and morphology suggesting the importance of these receptors in the modulation of reproduction in mammals. In this study we investigated the expression of delta opioid receptors on equine spermatozoa by western blot/indirect immunofluorescence and its relationship with sperm cell physiology. METHODS: We analyzed viability, motility, capacitation, acrosome reaction and mitochondrial activity in the presence of naltrindole and DPDPE by means of a computer assisted sperm analyzer and a fluorescent confocal microscope. The evaluation of viability, capacitation and acrosome reaction was carried out by the double CTC/Hoechst staining, whereas mitochondrial activity was assessed by means of MitoTracker Orange dye. RESULTS: We showed that in equine sperm cells, delta opioid receptor is expressed as a doublet of 65 and 50 kDa molecular mass and is localized in the mid piece of tail; we also demonstrated that naltrindole, a delta opioid receptor antagonist, could be utilized in modulating several physiological parameters of the equine spermatozoon in a dose-dependent way. We also found that low concentrations of the antagonist increase sperm motility whereas high concentrations show the opposite effect. Moreover low concentrations hamper capacitation, acrosome reaction and viability even if the percentage of cells with active mitochondria seems to be increased; the opposite effect is exerted at high concentrations. We have also observed that the delta opioid receptor agonist DPDPE is scarcely involved in affecting the same parameters at the employed concentrations. CONCLUSIONS: The results described in this paper add new important details in the comprehension of the mammalian sperm physiology and suggest new insights for improving reproduction and for optimizing equine breeding. PMID- 20579356 TI - Self-reported exposure to pesticides in residential settings and risk of breast cancer: a case-control study. AB - BACKGROUND: Pesticides are widely used in households to control insects and weeds. Several studies, over the past decades, have examined the possible relationship of serum concentration of organochlorine pesticides and the development of breast cancer. However, little data exists regarding an association between self-reported, residential exposure to pesticides and breast cancer risk. We, therefore, present a case-control study examining self-reported exposure to household pesticides with regard to associated risk of breast cancer. METHODS: This study was conducted in the area in and around New York City, NY and included 1205 patients (447 cases and 758 controls). Cases were defined as women with newly diagnosed breast cancer or carcinoma in-situ, while controls included women with benign breast diseases or those undergoing non-breast related surgery. All patients were asked a series of questions to determine their pesticide exposure, including the type of pesticide, location of exposure (inside vs. outside the home), who applied the pesticide (self vs. a professional) and duration of pesticide use. Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI). RESULTS: The most common pests encountered in participants' homes were ants, carpenter ants, and cockroaches. The calculated adjusted odds ratios for both self and professionally applied pesticides, specifically against the above mentioned insects, with regard to breast cancer risk were 1.25 (95% CI: 0.79-1.98) and 1.06 (95% CI: 0.65-1.73), respectively. Similarly, odds ratios and confidence intervals were calculated for other types of pesticides. CONCLUSIONS: Overall, the results of our study did not show an association between self reported exposure to pesticides and breast cancer risk. Future studies, utilizing a larger sample size and more specific detail on time frame of pesticide exposure, are needed to further explore this question. PMID- 20579357 TI - The LIFESTYLE study: costs and effects of a structured lifestyle program in overweight and obese subfertile women to reduce the need for fertility treatment and improve reproductive outcome. A randomised controlled trial. AB - BACKGROUND: In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome. METHODS/DESIGN: Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m2. Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders.In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient's weight. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs.Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group. DISCUSSION: The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1530. PMID- 20579358 TI - Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema--a long-term analysis from a Swiss perspective. AB - BACKGROUND: The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. METHODS: A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. RESULTS: Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions. CONCLUSION: The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost effective alternative for the therapy of CHE patients in Switzerland. PMID- 20579360 TI - Differentiation of human multipotent dermal fibroblasts into islet-like cell clusters. AB - BACKGROUND: We have previously obtained a clonal population of cells from human foreskin that is able to differentiate into mesodermal, ectodermal and endodermal progenies. It is of great interest to know whether these cells could be further differentiated into functional insulin-producing cells. RESULTS: Sixty-one single cell-derived dermal fibroblast clones were established from human foreskin by limiting dilution culture. Of these, two clones could be differentiated into neuron-, adipocyte- or hepatocyte-like cells under certain culture conditions. In addition, those two clones were able to differentiate into islet-like clusters under pancreatic induction. Insulin, glucagon and somatostatin were detectable at the mRNA and protein levels after induction. Moreover, the islet-like clusters could release insulin in response to glucose in vitro. CONCLUSIONS: This is the first study to demonstrate that dermal fibroblasts can differentiate into insulin producing cells without genetic manipulation. This may offer a safer cell source for future stem cell-based therapies. PMID- 20579359 TI - Construction of a medicinal leech transcriptome database and its application to the identification of leech homologs of neural and innate immune genes. AB - BACKGROUND: The medicinal leech, Hirudo medicinalis, is an important model system for the study of nervous system structure, function, development, regeneration and repair. It is also a unique species in being presently approved for use in medical procedures, such as clearing of pooled blood following certain surgical procedures. It is a current, and potentially also future, source of medically useful molecular factors, such as anticoagulants and antibacterial peptides, which may have evolved as a result of its parasitizing large mammals, including humans. Despite the broad focus of research on this system, little has been done at the genomic or transcriptomic levels and there is a paucity of openly available sequence data. To begin to address this problem, we constructed whole embryo and adult central nervous system (CNS) EST libraries and created a clustered sequence database of the Hirudo transcriptome that is available to the scientific community. RESULTS: A total of approximately 133,000 EST clones from two directionally-cloned cDNA libraries, one constructed from mRNA derived from whole embryos at several developmental stages and the other from adult CNS cords, were sequenced in one or both directions by three different groups: Genoscope (French National Sequencing Center), the University of Iowa Sequencing Facility and the DOE Joint Genome Institute. These were assembled using the phrap software package into 31,232 unique contigs and singletons, with an average length of 827 nt. The assembled transcripts were then translated in all six frames and compared to proteins in NCBI's non-redundant (NR) and to the Gene Ontology (GO) protein sequence databases, resulting in 15,565 matches to 11,236 proteins in NR and 13,935 matches to 8,073 proteins in GO. Searching the database for transcripts of genes homologous to those thought to be involved in the innate immune responses of vertebrates and other invertebrates yielded a set of nearly one hundred evolutionarily conserved sequences, representing all known pathways involved in these important functions. CONCLUSIONS: The sequences obtained for Hirudo transcripts represent the first major database of genes expressed in this important model system. Comparison of translated open reading frames (ORFs) with the other openly available leech datasets, the genome and transcriptome of Helobdella robusta, shows an average identity at the amino acid level of 58% in matched sequences. Interestingly, comparison with other available Lophotrochozoans shows similar high levels of amino acid identity, where sequences match, for example, 64% with Capitella capitata (a polychaete) and 56% with Aplysia californica (a mollusk), as well as 58% with Schistosoma mansoni (a platyhelminth). Phylogenetic comparisons of putative Hirudo innate immune response genes present within the Hirudo transcriptome database herein described show a strong resemblance to the corresponding mammalian genes, indicating that this important physiological response may have older origins than what has been previously proposed. PMID- 20579361 TI - Molecular understanding of sterically controlled compound release through an engineered channel protein (FhuA). AB - BACKGROUND: Recently we reported a nanocontainer based reduction triggered release system through an engineered transmembrane channel (FhuA Delta1-160; Onaca et al., 2008). Compound fluxes within the FhuA Delta1-160 channel protein are controlled sterically through labeled lysine residues (label: 3-(2 pyridyldithio)propionic-acid-N-hydroxysuccinimide-ester). Quantifying the sterical contribution of each labeled lysine would open up an opportunity for designing compound specific drug release systems. RESULTS: In total, 12 FhuA Delta1-160 variants were generated to gain insights on sterically controlled compound fluxes: Subset A) six FhuA Delta1-160 variants in which one of the six lysines in the interior of FhuA Delta1-160 was substituted to alanine and Subset B) six FhuA Delta1-160 variants in which only one lysine inside the barrel was not changed to alanine. Translocation efficiencies were quantified with the colorimetric TMB (3,3',5,5'-tetramethylbenzidine) detection system employing horseradish peroxidase (HRP). Investigation of the six subset A variants identified position K556A as sterically important. The K556A substitution increases TMB diffusion from 15 to 97 [nM]/s and reaches nearly the TMB diffusion value of the unlabeled FhuA Delta1-160 (102 [nM]/s). The prominent role of position K556 is confirmed by the corresponding subset B variant which contains only the K556 lysine in the interior of the barrel. Pyridyl labeling of K556 reduces TMB translocation to 16 [nM]/s reaching nearly background levels in liposomes (13 [nM]/s). A first B-factor analysis based on MD simulations confirmed that position K556 is the least fluctuating lysine among the six in the channel interior of FhuA Delta1-160 and therefore well suited for controlling compound fluxes through steric hindrance. CONCLUSIONS: A FhuA Delta1-160 based reduction triggered release system has been shown to control the compound flux by the presence of only one inner channel sterical hindrance based on 3-(2 pyridyldithio)propionic-acid labeling (amino acid position K556). As a consequence, the release kinetic can be modulated by introducing an opportune number of hindrances. The FhuA Delta1-160 channel embedded in liposomes can be advanced to a universal and compound independent release system which allows a size selective compound release through rationally re-engineered channels. PMID- 20579362 TI - Undifferentiated spondyloarthritis following allogeneic stem cell transplantation. AB - BACKGROUND: Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT. CASE PRESENTATION: We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation. CONCLUSION: Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s). PMID- 20579364 TI - Retrospective exposure assessment to airborne asbestos among power industry workers. AB - BACKGROUND: A method of individually assessing former exposure to asbestos fibres is a precondition of risk-differentiated health surveillance. The main aims of our study were to assess former levels of airborne asbestos exposure in the power industry in Germany and to propose a basic strategy for health surveillance and the early detection of asbestos related diseases. METHODS: Between March 2002 and the end of 2006, we conducted a retrospective questionnaire based survey of occupational tasks and exposures with airborne asbestos fibres in a cohort of 8632 formerly asbestos exposed power industry workers. The data on exposure and occupation were entered into a specially designed computer programme, based on ambient monitoring of airborne asbestos fibre concentrations. The cumulative asbestos exposure was expressed as the product of the eight-hour time weighted average and the total duration of exposure in fibre years (fibres/cubic centimetre-years). RESULTS: Data of 7775 (90% of the total) participants working in installations for power generation, power distribution or gas supply could be evaluated. The power generation group (n = 5284) had a mean age of 56 years, were exposed for 20 years and had an average cumulative asbestos exposure of 42 fibre years. The occupational group of "metalworkers" (n = 1600) had the highest mean value of 79 fibre years. The corresponding results for the power distribution group (n = 2491) were a mean age of 45 years, a mean exposure duration of 12 years and an average cumulative asbestos exposure of only 2.5 fibre years. The gas supply workers (n = 512) had a mean age of 54 years and a mean duration of exposure of 15 years. CONCLUSIONS: While the surveyed cohort as a whole was heavily exposed to asbestos dust, the power distribution group had a mean cumulative exposure of only 6% of that found in the power generation group. Based on the presented data, risk-differentiated disease surveillance focusing on metalworkers and electricians from the power generating industry seems justified. That combined with a sensitive examination technique would allow detecting asbestos related diseases early and efficiently. PMID- 20579363 TI - New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model. AB - INTRODUCTION: Avascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH. METHODS: Besides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC). RESULTS: Although rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS control), alpha-2-macroglobulin (A2M) gene was particularly over-expressed. Results were validated by RT-PCR and IHC. Importantly, A2M is known to share vascular, osteogenic and cartilage functions relevant for ANFH. CONCLUSIONS: The findings suggest that corticosteroid-induced ANFH in rats might be mediated by A2M. Investigation of A2M as a potential marker, and a treatment target, for early ANFH should be carried out. PMID- 20579365 TI - Spatiotemporal distribution of malaria and the association between its epidemic and climate factors in Hainan, China. AB - BACKGROUND: Hainan is one of the provinces most severely affected by malaria epidemics in China. The distribution pattern and major determinant climate factors of malaria in this region have remained obscure, making it difficult to target countermeasures for malaria surveillance and control. This study detected the spatiotemporal distribution of malaria and explored the association between malaria epidemics and climate factors in Hainan. METHODS: The cumulative and annual malaria incidences of each county were calculated and mapped from 1995 to 2008 to show the spatial distribution of malaria in Hainan. The annual and monthly cumulative malaria incidences of the province between 1995 and 2008 were calculated and plotted to observe the annual and seasonal fluctuation. The Cochran-Armitage trend test was employed to explore the temporal trends in the annual malaria incidences. Cross correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on malaria transmission and the auto correlation of malaria incidence. A multivariate time series analysis was conducted to construct a model of climate factors to explore the association between malaria epidemics and climate factors. RESULTS: The highest malaria incidences were mainly distributed in the central-south counties of the province. A fluctuating but distinctly declining temporal trend of annual malaria incidences was identified (Cochran-Armitage trend test Z = -25.14, P < 0.05). The peak incidence period was May to October when nearly 70% of annual malaria cases were reported. The mean temperature of the previous month, of the previous two months and the number of cases during the previous month were included in the model. The model effectively explained the association between malaria epidemics and climate factors (F = 85.06, P < 0.05, adjusted R(2) = 0.81). The autocorrelations of the fitting residuals were not significant (P > 0.05), indicating that the model extracted information sufficiently. There was no significant difference between the monthly predicted value and the actual value (t = -1.91, P = 0.08). The R(2) for predicting was 0.70, and the autocorrelations of the predictive residuals were not significant (P > 0.05), indicating that the model had a good predictive ability. DISCUSSION: Public health resource allocations should focus on the areas and months with the highest malaria risk in Hainan. Malaria epidemics can be accurately predicted by monitoring the fluctuations of the mean temperature of the previous month and of the previous two months in the area. Therefore, targeted countermeasures can be taken ahead of time, which will make malaria surveillance and control in Hainan more effective and simpler. This model was constructed using relatively long-term data and had a good fit and predictive validity, making the results more reliable than the previous report. CONCLUSIONS: The spatiotemporal distribution of malaria in Hainan varied in different areas and during different years. The monthly trends in the malaria epidemics in Hainan could be predicted effectively by using the multivariate time series model. This model will make malaria surveillance simpler and the control of malaria more targeted in Hainan. PMID- 20579366 TI - Ovarian matrix metalloproteinases are differentially regulated during the estrous cycle but not during short photoperiod induced regression in Siberian hamsters (Phodopus sungorus). AB - BACKGROUND: Matrix metalloproteinases (MMPs) are implicated as mediators for ovarian remodeling events, and are involved with ovarian recrudescence during seasonal breeding cycles in Siberian hamsters. However, involvement of these proteases as the photoinhibited ovary undergoes atrophy and regression had not been assessed. We hypothesized that 1) MMPs and their tissue inhibitors, the TIMPs would be present and differentially regulated during the normal estrous cycle in Siberian hamsters, and that 2) MMP/TIMP mRNA and protein levels would increase as inhibitory photoperiod induced ovarian degeneration. METHODS: MMP-2, 9, -14 and TIMP-1 and -2 mRNA and protein were examined in the stages of estrous (proestrus [P], estrus [E], diestrus I [DI], and diestrus II [DII]) in Siberian hamsters, as well as after exposure to 3, 6, 9, and 12 weeks of inhibitory short photoperiod (SD). RESULTS: MMP-9 exhibited a 1.6-1.8 fold decrease in mRNA expression in DII (p<0.05), while all other MMPs and TIMPs tested showed no significant difference in mRNA expression in the estrous cycle. Extent of immunostaining for MMP-2 and -9 peaked in P and E then significantly declined in DI and DII (p<0.05). Extent of immunostaining for MMP-14, TIMP-1, and TIMP-2 was significantly more abundant in P, E, and DI than in DII (p<0.05). Localization of the MMPs and TIMPs had subtle differences, but immunostaining was predominant in granulosa and theca cells, with significant differences noted in staining intensity between preantral follicles, antral follicles, corpora lutea, and stroma classifications. No significant changes were observed in MMP and TIMP mRNA or extent of protein immunostaining with exposure to 3, 6, 9, or 12 weeks of SD, however protein was present and was localized to follicular and luteal steroidogenic cells. CONCLUSIONS: Although MMPs appear to be involved in the normal ovarian estrus cycle at the protein level in hamsters, those examined in the present study are unlikely to be key players in the slow atrophy of tissue as seen in Siberian hamster ovarian regression. PMID- 20579367 TI - Association of ABO blood groups with Chikungunya virus. AB - Chikungunya virus (CHIKV) an emerging arboviral infection of public health concern belongs to the genus Alphavirus, family Togaviridae. Blood group antigens are generally known to act as receptors for various etiological agents. The studies defining the relationship between blood groups and CHIKV is limited and hence it is necessary to study these parameters in detail. In the present study 1500 subjects were enrolled and demographic data (Age, Gender, Blood group, CHIKV infection status, and CHIKV infection confirmation mode) was collected from them. The risk of acquiring CHIKV disease and its association with factors such as blood group, age and gender was analyzed statistically. The data of this study showed a possible association between blood group, age and gender of the study population with CHIKV infection. It is observed that CHIKV infections were higher in individuals with Rh positive blood group when compared to their Rh negative counterparts.CHIKV infections were found to be higher in Rh positive individuals of AB and A blood groups than that of Rh negative counterparts. Results also indicated that infections were higher in adults belonging to the age group > 30 years and also higher in males as compared to females enrolled in this study. These data present further evidence for the association of the blood groups, age and gender to susceptibility to CHIKV infection. Further studies are needed to confirm these findings. This is the second study showing the possible association of blood groups with chikungunya. PMID- 20579368 TI - Species delineation using Bayesian model-based assignment tests: a case study using Chinese toad-headed agamas (genus Phrynocephalus). AB - BACKGROUND: Species are fundamental units in biology, yet much debate exists surrounding how we should delineate species in nature. Species discovery now requires the use of separate, corroborating datasets to quantify independently evolving lineages and test species criteria. However, the complexity of the speciation process has ushered in a need to infuse studies with new tools capable of aiding in species delineation. We suggest that model-based assignment tests are one such tool. This method circumvents constraints with traditional population genetic analyses and provides a novel means of describing cryptic and complex diversity in natural systems. Using toad-headed agamas of the Phrynocephalus vlangalii complex as a case study, we apply model-based assignment tests to microsatellite DNA data to test whether P. putjatia, a controversial species that closely resembles P. vlangalii morphologically, represents a valid species. Mitochondrial DNA and geographic data are also included to corroborate the assignment test results. RESULTS: Assignment tests revealed two distinct nuclear DNA clusters with 95% (230/243) of the individuals being assigned to one of the clusters with >90% probability. The nuclear genomes of the two clusters remained distinct in sympatry, particularly at three syntopic sites, suggesting the existence of reproductive isolation between the identified clusters. In addition, a mitochondrial ND2 gene tree revealed two deeply diverged clades, which were largely congruent with the two nuclear DNA clusters, with a few exceptions. Historical mitochondrial introgression events between the two groups might explain the disagreement between the mitochondrial and nuclear DNA data. The nuclear DNA clusters and mitochondrial clades corresponded nicely to the hypothesized distributions of P. vlangalii and P. putjatia. CONCLUSIONS: These results demonstrate that assignment tests based on microsatellite DNA data can be powerful tools for distinguishing closely related species and support the validity of P. putjatia. Assignment tests have the potential to play a significant role in elucidating biodiversity in the era of DNA data. Nonetheless, important limitations do exist and multiple independent datasets should be used to corroborate results from assignment programs. PMID- 20579369 TI - Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry. AB - BACKGROUND: Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency. RESULTS: We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties. CONCLUSIONS: For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics. PMID- 20579370 TI - Development of an awareness-based intervention to enhance quality of life in severe dementia: trial platform. AB - BACKGROUND: Quality of residential care for people with severe dementia is in urgent need of improvement. One reason for this may be the assumption that people with severe dementia are unaware of what is happening to them. However, there is converging evidence to suggest that global assumptions of unawareness are inappropriate. This trial platform study aims to assist care staff in perceiving and responding to subtle signs of awareness and thus enhance their practice. METHODS/DESIGN: In Stage One, a measure of awareness in severe dementia will be developed. Two focus groups and an expert panel will contribute to item and scale development. In Stage Two observational data will be used to further develop the measure. Working in four care homes, we will recruit 40 individuals with severe dementia who have no, or very limited, verbal communication. Data on inter-rater reliability and frequency of all items and exploratory factor analysis will be used to identify items to be retained. Test-retest and inter-rater reliability for the new measure will be calculated. Correlations with scores for well-being and behaviour and with proxy ratings of quality of life will provide an indication of concurrent validity. In Stage Three the new measure will be used in a single blind cluster randomised trial. Eight care homes will participate, with 10 residents recruited in each giving a total sample of 80 people with severe dementia. Homes will be randomised to intervention or usual care conditions. In the intervention condition, staff will receive training in using the new measure and will undertake observations of designated residents. For residents with dementia, outcomes will be assessed in terms of change from baseline in scores for behaviour, well-being and quality of life. For care staff, outcomes will be assessed in terms of change from baseline in scores for attitudes, care practice, and well-being. DISCUSSION: The results will inform the design of a larger-scale trial intended to provide definitive evidence about the benefits of increasing the sensitivity of care staff to signs of awareness in residents with severe dementia. TRIAL REGISTRATION: ISRCTN59507580 http://www.controlled-trials.com. PMID- 20579371 TI - Molecular evolution of glutamine synthetase II: Phylogenetic evidence of a non endosymbiotic gene transfer event early in plant evolution. AB - BACKGROUND: Glutamine synthetase (GS) is essential for ammonium assimilation and the biosynthesis of glutamine. The three GS gene families (GSI, GSII, and GSIII) are represented in both prokaryotic and eukaryotic organisms. In this study, we examined the evolutionary relationship of GSII from eubacterial and eukaryotic lineages and present robust phylogenetic evidence that GSII was transferred from gamma-Proteobacteria (Eubacteria) to the Chloroplastida. RESULTS: GSII sequences were isolated from four species of green algae (Trebouxiophyceae), and additional green algal (Chlorophyceae and Prasinophytae) and streptophyte (Charales, Desmidiales, Bryophyta, Marchantiophyta, Lycopodiophyta and Tracheophyta) sequences were obtained from public databases. In Bayesian and maximum likelihood analyses, eubacterial (GSIIB) and eukaryotic (GSIIE) GSII sequences formed distinct clades. Both GSIIB and GSIIE were found in chlorophytes and early diverging streptophytes. The GSIIB enzymes from these groups formed a well supported sister clade with the gamma-Proteobacteria, providing evidence that GSIIB in the Chloroplastida arose by horizontal gene transfer (HGT). Bayesian relaxed molecular clock analyses suggest that GSIIB and GSIIE coexisted for an extended period of time but it is unclear whether the proposed HGT happened prior to or after the divergence of the primary endosymbiotic lineages (the Archaeplastida). However, GSIIB genes have not been identified in glaucophytes or red algae, favoring the hypothesis that GSIIB was gained after the divergence of the primary endosymbiotic lineages. Duplicate copies of the GSIIB gene were present in Chlamydomonas reinhardtii, Volvox carteri f. nagariensis, and Physcomitrella patens. Both GSIIB proteins in C. reinhardtii and V. carteri f. nagariensis had N-terminal transit sequences, indicating they are targeted to the chloroplast or mitochondrion. In contrast, GSIIB proteins of P. patens lacked transit sequences, suggesting a cytosolic function. GSIIB sequences were absent in vascular plants where the duplication of GSIIE replaced the function of GSIIB. CONCLUSIONS: Phylogenetic evidence suggests GSIIB in Chloroplastida evolved by HGT, possibly after the divergence of the primary endosymbiotic lineages. Thus while multiple GS isoenzymes are common among members of the Chloroplastida, the isoenzymes may have evolved via different evolutionary processes. The acquisition of essential enzymes by HGT may provide rapid changes in biochemical capacity and therefore be favored by natural selection. PMID- 20579372 TI - Arterial hypertension due to fructose ingestion: model based on intermittent osmotic fluid trapping in the small bowel. AB - Based on recently reported data that fructose ingestion is linked to arterial hypertension, a model of regulatory loops involving the colon role in maintenance of fluid and sodium homeostasis is proposed.In normal digestion of hyperosmolar fluids, also in cases of postprandial hypotension and in patients having the "dumping" syndrome after gastric surgery, any hyperosmolar intestinal content is diluted by water taken from circulation and being trapped in the bowel until reabsorption. High fructose corn sirup (HFCS) soft drinks are among common hyperosmolar drinks. Fructose is slowly absorbed through passive carrier-mediated facilitated diffusion, along the entire small bowel, thus preventing absorption of the trapped water for several hours.Here presented interpretation is that ingestion of hyperosmolar HFCS drinks due to a transient fluid shift into the small bowel increases renin secretion and sympathetic activity, leading to rise in ADH and aldosterone secretions. Their actions spare water and sodium in the large bowel and kidneys. Alteration of colon absorption due to hormone exposure depends on cell renewal and takes days to develop, so the momentary capacity of sodium absorption in the colon depends on the average aldosterone and ADH exposure during few previous days. This inertia in modulation of the colon function can make an individual that often takes HFCS drinks prone to sodium retention, until a new balance is reached with an expanded ECF pool and arterial hypertension. In individuals with impaired fructose absorption, even a higher risk of arterial hypertension can be expected. PMID- 20579373 TI - The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion. AB - BACKGROUND: The alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC). METHODS: To determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin alpha4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin alpha4 or FAK in CS1-mediated cell spreading and migration, respectively. RESULTS: CS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS 1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin alpha4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1 induced cell migration. CONCLUSION: These data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion. PMID- 20579374 TI - Neglected simultaneous bilateral femoral neck fractures secondary to narcotic drug abuse treated by bilateral one-staged hemiarthroplasty: a case report. AB - Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid or renal dysfunction, anti epileptic medications, seizure, etc. A 28-year-old addict man referred to us with a 10-year history of narcotic drug abuse and history of 8 months bilateral groin pain. He admitted with displaced bilateral femoral neck fracture. Because of long duration of this condition and osteonecrosis revealed on bone scan, one-staged bilateral hip hemiarthroplasty was done. A good function was noted after surgery to 4-month follow up. Up to now, have not be founded in the literature that a case of bilateral femoral neck fracture associated with narcotic drug abuse.Because of negative effects of opium or smoking on bone tissues, a simple bone pain should aware us about the risk of stress or fatigue fracture. PMID- 20579375 TI - EpCAM nuclear localization identifies aggressive thyroid cancer and is a marker for poor prognosis. AB - BACKGROUND: Proteolytic cleavage of the extracellular domain (EpEx) of Epithelial cell adhesion molecule (EpCAM) and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. METHODS: EpEx, Ep-ICD and beta-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC) tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. RESULTS: The anaplastic (ATC) and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC) showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and beta-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS) for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. CONCLUSION: We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC. PMID- 20579376 TI - Modular composition predicts kinase/substrate interactions. AB - BACKGROUND: Phosphorylation events direct the flow of signals and metabolites along cellular protein networks. Current annotations of kinase-substrate binding events are far from complete. In this study, we scanned the entire human protein sequences using the PROSITE domain annotation tool to identify patterns of domain composition in kinases and their substrates. We identified statistically enriched pairs of strings of domains (signature pairs) in kinase-substrate couples presented in the 2006 version of the PTM database. RESULTS: The signature pairs enriched in kinase - substrate binding interactions turned out to be highly specific to kinase subtypes. The resulting list of signature pairs predicted kinase-substrate interactions in validation dataset not used in learning with high statistical accuracy. CONCLUSIONS: The method presented here produces predictions of protein phosphorylation events with high accuracy and mid-level coverage. Our method can be used in expanding the currently available drafts of cell signaling pathways and thus will be an important tool in the development of combination drug therapies targeting complex diseases. PMID- 20579377 TI - Acute camptocormia induced by olanzapine: a case report. AB - INTRODUCTION: Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder. CASE PRESENTATION: A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L). Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later. CONCLUSIONS: Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug-induced rhabdomyolysis, in patients presenting with acute onset bent spine syndrome. Although rare, the occurrence of camptocormia induced by olanzapine must be considered. PMID- 20579378 TI - EGFR isoforms and gene regulation in human endometrial cancer cells. AB - BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation. RESULTS: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. Sequence of the EGFR tyrosine kinase domain proved to be wild type in both cell lines. While both cell lines expressed full-length EGFR (isoform A), EGFR and sEGFR (isoform D) were expressed at significantly lower levels in Hec50co cells compared to Ishikawa H cells. Analysis of gene expression following EGF vs. gefitinib treatment (a small molecule EGFR tyrosine kinase inhibitor) was performed. Early growth response 1, sphingosine kinase 2, dual specificity phosphatase 6, and glucocorticoid receptor DNA binding factor 1 are members of a cluster of genes downstream of EGFR that are differentially regulated by treatment with EGF compared to gefitinib in Ishikawa H cells, but not in Hec50co cells. CONCLUSIONS: Type I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGF or gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade. PMID- 20579379 TI - Risk factors for posttraumatic stress disorder among deployed US male marines. AB - BACKGROUND: Combat exposure has been reported as one of the strongest risk factors for postdeployment posttraumatic stress disorder (PTSD) among military service members. Determining the impact of specific deployment-related exposures on the risk of developing PTSD has not been fully explored. Our study objective was to explore the relationship between specific combat exposures and other life experiences with postdeployment PTSD. METHODS: This study consisted of male Marines who completed a Recruit Assessment Program (RAP) survey during recruit training at the Marine Corps Recruit Depot in San Diego, California as well as a follow-up survey several years after recruit training. Study participants included those Marines who deployed to the current operations in Iraq or Afghanistan between the baseline and follow-up surveys. Multivariable logistic regression was performed to determine which significant exposures and experiences were associated with postdeployment PTSD. RESULTS: Of the 706 study participants, 10.8% screened positive for postdeployment PTSD. Those who reported feeling in great danger of death (odds ratio [OR] = 4.63, 95% confidence interval [CI]: 2.46 8.73), were shot or seriously injured (OR = 3.51, 95% CI: 1.58-7.77), saw someone wounded or killed (OR = 2.47, 95% CI: 1.08-5.67), and baseline (before recruit training) prior violence exposures (OR = 2.99, 95% CI: 1.46-6.10) were at increased odds for reporting PTSD symptoms. Number of deployments, number of close friends or relatives reported at follow-up, and enlisted pay grade were also significantly associated with postdeployment PTSD. CONCLUSIONS: Combat exposures, specifically the threat of death, serious injury, and witnessing injury or death are significant risk factors for screening positive for postdeployment PTSD among male Marines as well as violence exposures prior to entering the Marine Corps, which are independent of future combat exposures. A thorough history of lifetime violence exposures should be pursued when considering a clinical diagnosis of PTSD. PMID- 20579380 TI - Are time-trends of smoking among pregnant immigrant women in Sweden determined by cultural or socioeconomic factors? AB - BACKGROUND: The widening socioeconomic gap in smoking during pregnancy remains a challenge to the Swedish antenatal care services. However, the influence of cultural factors in explaining the socioeconomic differences in smoking during pregnancy is not clear among the immigrant women. The aim of this study was to investigate whether the development of smoking prevalence among pregnant immigrant women in Sweden followed the trajectory which could be expected from the stages of the global smoking epidemic model in the women's countries of origin, or not. METHODS: Delivery data on pregnancies in Sweden from 1982 to 2001 was collected from the Swedish Medical Birth Registry. From a total of 2,224,469 pregnant women during this period, all immigrant pregnant women (n = 234,731) were selected to this study. A logistic regression analysis and attributable fraction were used to investigate the association between smoking during pregnancy and the socioeconomic differences among immigrant women. RESULTS: Overall, the prevalence of smoking among pregnant immigrant women decreased from 30.3% in 1982 to 11.0% in 2001, albeit with remarkable differences between educational levels and country of origin. The greatest decline of absolute prevalence was recorded among low educated women (27.9%) and among other Nordic countries (17.9%). In relative terms, smoking inequalities increased between educational levels regardless of country of origin. The odds ratios for low educational level for women from other Nordic countries increased from 4.9 (95% CI 4.4-5.4) in 1982 to 13.4 (95% CI 11.2-16.2) in 2001, as compared to women with high education in the same group. Further, the total attributable fraction for educational difference increased from 55% in 1982 to 62% in 2001, demonstrating the strong effect of educational attainment. CONCLUSIONS: Our hypothesis that the socioeconomic time trend of smoking based on the stage of the world wide tobacco epidemic model related to country of origin of the immigrant women was not supported by our analyses. Our findings does not support a call for specific "culture sensitive" antismoking policies or interventions in Sweden or similar countries, but reinforce the existing evidence with a focus on women with a low educational level, regardless of cultural background. PMID- 20579381 TI - Evaluation of the criteria for angiotomography indications in the diagnosis of carotid and vertebral arterial injury associated with blunt trauma. AB - BACKGROUND: Blunt carotid and vertebral artery injury (BCVI) occur infrequently. The incidence of this type of injury is difficult to determine as many emergency room patients are neurologically asymptomatic. The statistics have not been reported in Brazil. The objectives of the current study were: To evaluate the accuracy of criteria used to recommend angiotomography in the diagnosis of cervical BCVI in 100 patients with blunt cervical trauma in the trauma services section of a Brazilian quaternary care hospital. METHODS: During a 30-month (2006 2008), all patients admitted to the emergency room of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo with blunt cervical trauma and potential risk of cervical vessel injury, were subjected to cervical angiotomography to diagnose BCVI. The data analyzed are presented as mean +/- standard deviation, and statistical analyses included Chi-square and Fisher's exact tests, and the Mann-Whitney test. RESULTS: During the study period 2467 blunt trauma patients were admitted. In 100 patients that met the criteria for inclusion in the study, angiotomography identified 23 with BCVI, including 17 males and six females. The mean patient age was 34.81 +/- 14.84 years. Car crash (49%) and car-pedestrian accidents (24%) were the most frequent causes of injury. Ten patients had internal carotid artery injuries, two patients had common carotid artery injuries, and 11 patients had vertebral artery injuries. Seven patients presented with Degree I arterial injuries, 10 patients presented with Degree II artery injuries, four patients presented with Degree IV artery injuries, one patient presented with a Degree V artery injury, and one patient had a carotid fistula. Seven out of the 23 patients with BCVI (30.4%) presented with cervical vertebrae fractures, and 11 out of the 23 patients with BCVI (47.8%) presented with facial fractures (LeFort II and III). CONCLUSIONS: Although there is no consensus regarding the criteria that should be used to indicate angiotomography for BCVI diagnosis, we conclude that the criteria used in the current study led to a diagnosis of BCVI in 0.93% of 2,467 trauma patients, BCVI injuries were associated with more severe traumas and did not affect mortality. PMID- 20579382 TI - Genetic diversity of Mycobacterium tuberculosis Complex in Jos, Nigeria. AB - BACKGROUND: Nigeria has a high tuberculosis incidence, and genotyping studies of Mycobacterium tuberculosis Complex (MTC) in the country are necessary in order to improve our understanding of the epidemic. METHODS: Isolates of MTC were isolated from cases of pulmonary tuberculosis in Jos, North Central region of Nigeria during 2006-2008. Drug susceptibility test (DST) was performed on 77 of 111 isolates by proportion method on Lowenstein Jensen (LJ) slope while genotyping of mycobacterial DNA was performed by spoligotyping. The SpolDB4 database and the model-based program 'spotclust' were used to assign isolates to families, subfamilies and variants. RESULTS: A total of 111 pulmonary isolates from consecutive tuberculosis patients in the city of Jos, Plateau State, Nigeria were spoligotyped. A total of 84 (76%) of the isolates belonged to the Latin American Mediterranean (LAM) family. Of these, 78 isolates were assigned to the LAM10 lineage. Among these, 66 exhibited identical spoligopatterns. Drug susceptibility profiles obtained were not consistently associated with any spoligopattern. CONCLUSIONS: The dominance of few M. tuberculosis lineages suggests either a high rate of transmission, frequent import of closely related strains, or a highly conserved genotype. It remains to be confirmed whether the predominance of identical LAM10 represent an outbreak.Spoligotyping was useful to gain an overall understanding of the local TB epidemic. This study demonstrated that the incidence of TB in Jos, Nigeria may be caused by a few successful M. tuberculosis families, dominated by the LAM10 family. PMID- 20579383 TI - Oral and inhaled sodium cromoglicate in the management of systemic mastocytosis: a case report. AB - INTRODUCTION: Mastocytosis is a rare disease consisting of a group of disorders characterized by a pathologic increase in the number of mast cells in one or more organ system. Treatment is symptomatic. Oral sodium cromoglicate (SCG) is the only treatment licensed for the treatment of mastocytosis. In this case we report how in a mastocytosis patient being treated with H1 and H2 antihistamines, and oral sodium cromoglicate, the addition of inhaled sodium cromoglicate resulted in further improvement. This is the first report of this use of the drug in this disease. CASE PRESENTATION: The subject is a Caucasian woman aged 40 years. Symptoms of mastocytosis began when she was aged 13 years, but the diagnosis was not made until after her first pregnancy aged 33 years. Symptoms improved with H1 and H2 antihistamines, and oral sodium cromoglicate, but it required the addition of inhaled sodium cromoglicate to produce further improvement, specifically in the symptoms of bone pain, fatigue and headache. Doses of oral sodium cromoglicate had to be increased if challenged with a food to which the subject was sensitive. Doses of inhaled sodium cromoglicate had to be increased during the menstrual period. CONCLUSIONS: Patients suffering from the rare disease of mastocytosis have symptoms affecting many body systems. Symptoms result from the release of inflammatory mediators from mast cells. Sodium cromoglicate, a drug that reduces the release of mediators from mast cells, is effective in controlling gastrointestinal symptoms, but less effective in those affecting other body systems. In this case report we have shown that the addition of inhaled sodium cromoglicate controls the symptoms of bone pain, fatigue and headache and also that the doses have to be increased during the menstrual period. PMID- 20579384 TI - 3066 consecutive Gamma Nails. 12 years experience at a single centre. AB - BACKGROUND: Fixation of trochanteric hip fractures using the Gamma Nail has been performed since 1988 and is today well established and wide-spread. However, a number of reports have raised serious concerns about the implant's complication rate. The main focus has been the increased risk of a subsequent femoral shaft fracture and some authors have argued against its use despite other obvious advantages, when this implant is employed. Through access to a uniquely large patient data base available, which is available for analysis of trochanteric fractures; we have been able to evaluate the performance of the Gamma Nail over a twelve year period. METHODS: 3066 consecutive patients were treated for trochanteric fractures using Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l'Orthopedie (CTO), Strasbourg, France. These patients were retrospectively analysed. Information on epidemiological data, intra- and postoperative complications and patients' outcome was retrieved from patient notes. All available radiographs were assessed by a single reviewer (AJB). RESULTS: The results showed a low complication rate with the use of the Gamma Nail. There were 137 (4.5%) intraoperative fracture-related complications. Moreover 189 (6.2%) complications were detected postoperatively and during follow up. Cut-out of the lag screw from the femoral head was the most frequent mechanical complication (57 patients, 1.85%), whereas a postoperative femoral shaft fracture occurred in 19 patients (0.6%). Other complications, such as infection, delayed healing/non-union, avascular femoral head necrosis and distal locking problems occurred in 113 patients (3.7%). CONCLUSIONS: The use of the Gamma Nail in trochanteric hip fractures is a safe method with a low complication rate. In particular, a low rate of femoral shaft fractures was reported. The low complication rate reported in this series can probably be explained by strict adherence to a proper surgical technique. PMID- 20579385 TI - Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer. AB - BACKGROUND: A substantial number of microRNAs (miRNAs) is subject to epigenetic silencing in cancer. Although epigenetic silencing of tumour suppressor genes is an important feature of cervical cancer, little is known about epigenetic silencing of miRNAs. Since DNA methylation-based silencing of hsa-miR-124 occurs in various human cancers, we studied the frequency and functional effects of hsa miR-124 methylation in cervical carcinogenesis. RESULTS: Quantitative MSP analysis of all 3 loci encoding the mature hsa-miR-124 (hsa-miR-124-1/-2/-3) showed methylation in cervical cancer cell lines SiHa, CaSki and HeLa as well as in late passages of human papillomavirus (HPV) type 16 or 18 immortalised keratinocytes. Treatment of SiHa cells with a demethylating agent reduced hsa-miR 124 methylation levels and induced hsa-miR-124 expression. In HPV-immortalised keratinocytes increased methylation levels were related to reduced hsa-miR-124 expression and higher mRNA expression of IGFBP7, a potential hsa-miR-124 target gene. Ectopic hsa-miR-124 expression in SiHa and CaSki cells decreased proliferation rates and migratory capacity. Combined hsa-miR-124-1 and/or hsa-miR 124-2 methylation analysis of 139 cervical tissue specimens showed an increasing methylation frequency from 0% in normal tissues up to 93% in cervical carcinomas. Increased methylation levels of hsa-miR-124-1 and hsa-miR-124-2 were significantly correlated with reduced hsa-miR-124 expression in cervical tissue specimens. Combined hsa-miR-124-1 and/or hsa-miR-124-2 methylation analysis of 43 cervical scrapes of high-risk HPV positive women was predictive of underlying high-grade lesions. CONCLUSIONS: DNA methylation-based silencing of hsa-miR-124 is functionally involved in cervical carcinogenesis and may provide a valuable marker for improved detection of cervical cancer and its high-grade precursor lesions. PMID- 20579386 TI - A simple way to evaluate self-designed probes for tumor specific Multiplex Ligation-dependent Probe Amplification (MLPA). AB - BACKGROUND: The Multiplex Ligation-dependent Probe Amplification (MLPA) is widely used for analysis of copy number variations (CNVs) in single or multiple loci. MLPA is a versatile methodology and important tool in cancer research; it provides precise information on increased or decreased copy number at specific loci as opposed to loss of heterozygosity (LOH) studies based upon microsatellite analysis. Pre-designed MLPA kits and software are commercially available to analyze multiple exons, genes, and genomic regions. However, an increasing demand for new gene specific assays makes it necessary to self-design new MLPA probes for which the available software may not be applicable. During evaluation of new self-designed reference probes, we encountered a number of problems, especially when applying the MLPA methodology to tumor samples. FINDINGS: DNA samples from 48 unaffected individuals and 145 breast cancer patients were used to evaluate 11 self-designed MLPA probes and determine the cut-off values for CNV, before applying the MLPA probes to normalize the target probes in a cohort of affected individuals. To test the calculation strategy, three probes were designed to cover regions in Regulator of G-protein Signaling 8 (RGS8), which we previously have identified as being affected by allelic imbalance by LOH analysis across RGS8 in the cohort comprising 145 breast tumors. Agreement between the LOH results and the results obtained by each of the three MLPA probes in RGS8 was found for 64%, 73%, and 91%, of the analyzed samples, respectively. CONCLUSION: Here, we present a straightforward method, based upon the normalization pattern in both unaffected and affected individuals, to evaluate self-designed reference probes and to calculate CNV for the MLPA assay with specific focus on the difficulties when analyzing tumor DNA. PMID- 20579387 TI - Prognostic value of HMGB1 overexpression in resectable gastric adenocarcinomas. AB - INTRODUCTION: HMGB1(High mobility group box 1), originally described as a nuclear protein, is now regarded as a multifunctional protein with a paradoxical dual effect in tumors. In the present study, HMGB1 overexpression and its correlation with the clinicopathologic characteristics and recurrence-free survival were evaluated in gastric adenocarcinomas. METHODS: 76 gastric adenocarcinomas surgically removed entered the study. The immunohistochemical staining was used to assess HMGB1 expression through tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded, and the regular follow-up was made for all patients. RESULTS: Almost all the gastric adenocarcinomas showed HMGB1 positive staining mainly in the nucleus, and the overexpression of HMGB1 was found in cancerous tissues with higher strong reactivity rate, compared with non-cancerous tissues (total expression score >or= 9, 42.0% vs. 9.0%, P < 0.001). Survival analysis revealed that tumor stage negatively correlated with cancer-free survival (P = 0.022). Furthermore, HMGB1 overexpression positively associated with cancer-free survival of resectable gastric adenocarcinomas (P = 0.023). CONCLUSIONS: The overexpression of HMGB1 protein indicates that HMGB1 may play a role in the tumorigenesis of gastric adenocarcinomas. And the overexpression of HMGB1 may be a marker of good prognosis of gastric adenocarcinoma given curative resection combined with adjuvant chemotherapy. PMID- 20579388 TI - Using a Caesarean Section Classification System based on characteristics of the population as a way of monitoring obstetric practice. AB - OBJECTIVE: to compare the distribution of caesarean rates in the Robson's 10 groups classification in order to see if any change occurred after the implementation of an audit and feedback intervention. DESIGN: cross sectional, before and after an audit and feedback study. SETTING: a university hospital in Brazil. METHODS: clinical records of all births during two three months-periods were evaluated. Each case of CS was classified into one of ten mutually exclusive categories according to obstetric characteristics. The proportion of CS in each group was compared in both periods. RESULTS: total number of deliveries and the high rate of CS were similar in both periods. Group 3 (multiparous excluding previous CS, single, cephalic, >/= 37 weeks, spontaneous labour) accounted for the largest proportion of deliveries, 28.5 and 26.8% in both periods. Group 1 (nulliparous, single, cephalic, >/= 37 weeks, spontaneous labour) was the second largest one, while Group 5 (previous caesarean section, single, cephalic, and >/= 37 weeks) was the third but the largest contributor to CS, accounting for 16.6 and 14.9% among all deliveries in both periods. Groups 2 (nulliparous, single, cephalic, >/= 37 weeks, induction or CS before labour) and 4 (multiparous excluding previous CS, single, cephalic, >/= 37 weeks, induction or CS before labour) were less prevalent, however had higher rates of CS. Only in Group 10 (All single, cephalic, 7.5%. CONCLUSIONS: Chronic complications are highly prevalent among type 2 diabetic outpatients, the glycemic control of diabetic patients with chronic complications was poor, and future efforts should be directed at intensive blood glucose control, strengthening early diagnosis and improving case management to prevent and minimize the occurrence of complications. PMID- 20579391 TI - Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. AB - Cancer associated fibroblasts (CAFs) play a critical role for growth, invasion, and metastasis of cancer. Therefore, targeting CAFs with small molecule inhibitors may be an attractive anti-tumor strategy. The current study aims to identify small molecule kinase inhibitors affecting CAF's growth and to characterize the biological effects of active compounds on primary CAFs from lung cancer. We screened two individual CAF strains for their sensitivity to a panel of 160 kinase inhibitors. Five kinase inhibitors were identified inhibiting more than 50% of the growth of both cell lines. Three of them were inhibitors of PDGFR at nanomolar concentrations. Therefore, we further tested the FDA approved PDGFR inhibitors Dasatinib, Nilotinib, Sorafenib, and Imatinib. All 37 CAF strains investigated were highly sensitive to Dasatinib at clinically relevant concentrations. Imatinib was slightly less effective, whereas the inhibitory effects of Nilotinib and Sorafenib were significantly less pronounced.We investigated the effect of Dasatinib on the CAF transcriptome by microarray analysis of 9 individual CAF strains. 492 genes were identified whose expression was changed at least twofold. 104 of these encoded cell cycle related proteins with 97 of them being downregulated by Dasatinib. The majority of regulated genes, however, were of diverse biological functions not directly related to proliferation. We compared this Dasatinib expression signature to previously described differential signatures of normal tissue associated fibroblasts (NAFs) and CAFs and to a signature of fibroblast serum response. There was a significant overlap between genes regulated by Dasatinib and serum repression genes. More importantly, of the 313 genes downregulated by Dasatinib 64 were also reduced in NAFs compared to CAFs. Furthermore, 26 of 179 genes identified as upregulated by Dasatinib were also found to be elevated in NAFs compared to CAFs. These data demonstrate that Dasatinib partially reverses the phenotype of CAFs to a normal fibroblast like phenotype. This is further supported by the finding that incubation of tumor cells with conditioned medium from CAFs pre-incubated with Dasatinib significantly reduced tumor cell proliferation, suggesting that Dasatinib partially reverses the CAF mediated tumor promoting effect. Therefore, targeting CAFs with Dasatinib represents a promising therapeutic principle. PMID- 20579392 TI - Effect of incentives on insecticide-treated bed net use in sub-Saharan Africa: a cluster randomized trial in Madagascar. AB - BACKGROUND: Insecticide-treated bed nets (ITNs) have been shown to reduce morbidity and mortality due to malaria in sub-Saharan Africa. Strategies using incentives to increase ITN use could be more efficient than traditional distribution campaigns. To date, behavioural incentives have been studied mostly in developed countries. No study has yet looked at the effect of incentives on the use of ITNs. Reported here are the results of a cluster randomized controlled trial testing household-level incentives for ITN use following a free ITN distribution campaign in Madagascar. METHODS: The study took place from July 2007 until February 2008. Twenty-one villages were randomized to either intervention or control clusters. Households in both clusters received a coupon redeemable for one ITN. After one month, intervention households received a bonus for ITN use, determined by visual confirmation of a mounted ITN. Data were collected at baseline, one month and six months. Both unadjusted and adjusted results, using cluster specific methods, are presented. RESULTS: At baseline, 8.5% of households owned an ITN and 6% were observed to have a net mounted over a bed in the household. At one month, there were no differences in ownership between the intervention and control groups (99.5% vs. 99.4%), but net use was substantially higher in the intervention group (99% vs. 78%), with an adjusted risk ratio of 1.24 (95% CI: 1.10 to 1.40; p < 0.001). After six months, net ownership had decreased in the intervention compared to the control group (96.7% vs. 99.7%), with an adjusted risk ratio of 0.97 (p < 0.01). There was no difference between the groups in terms of ITN use at six months; however, intervention households were more likely to use a net that they owned (96% vs. 90%; p < 0.001). CONCLUSIONS: Household-level incentives have the potential to significantly increase the use of ITNs in target households in the immediate-term, but, over time, the use of ITNs is similar to households that did not receive incentives. Providing incentives for behaviour change is a promising tool that can complement traditional ITN distribution programmes and improve the effectiveness of ITN programmes in protecting vulnerable populations, especially in the short-term. PMID- 20579393 TI - Assessment of nodal target definition and dosimetry using three different techniques: implications for re-defining the optimal pelvic field in endometrial cancer. AB - PURPOSES: 1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning techniques applied to this new CTV and the surrounding tissues. METHODS AND MATERIALS: Based on the literature, we selected a methodology to delineate nodal target volume to define a NEW-CTV and NEW-PTV. Conventional 2D fields, 3D fields based on anatomic guidelines per RTOG 0418, 3D fields based on our guidelines, and IMRT based on our guidelines were assessed for coverage of NEW-CTV, NEW-PTV, and surrounding structures. CT scans of 10 patients with gynecologic malignancies after TAH/BSO were used. DVHs were compared. RESULTS: For NEW-PTV, mean V45Gy were 50% and 69% for 2D and RTOG 0418 3DCRT vs. 98% and 97% for NEW-3DCRT and NEW-IMRT (p < 0.0009). Mean V45Gy small bowel were 24% and 20% for 2D and RTOG 0418-3DCRT, increased to 32% with NEW 3DCRT, and decreased to 14% with IMRT (p = 0.005, 0.138, 0.002). Mean V45Gy rectum were 26%, 35%, and 52% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 26% with NEW-IMRT (p < 0.05). Mean V45Gy bladder were 83%, 51%, and 73% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 30% with NEW-IMRT (p < 0.002). CONCLUSIONS: Conventional 2D and RTOG 0418-based 3DCRT plans cover only a fraction of our comprehensive PTV. A 3DCRT plan covers this PTV with high doses to normal tissues, whereas IMRT covers the PTV while delivering lower normal tissue doses. Re-consideration of what specifically the pelvic target encompasses is warranted. PMID- 20579394 TI - Characterization of bone repair in rat femur after treatment with calcium phosphate cement and autogenous bone graft. AB - BACKGROUND: In this study, the biocompatibility, stability and osteotransductivity of a new cement based on alpha-tricalcium phosphate (alpha TCP) were investigated in a bone repair model using a rat model. METHODS: The potential of alpha-TCP on bone repair was compared to autogenous bone grafting, and unfilled cavities were used as negative control. Surgical cavities were prepared and designated as test (T), implanted with alpha-TCP blocks; negative control (C - ), unfilled; and positive control (C + ), implanted with autogenous bone graft. Results were analyzed on postoperative days three, seven, 14, 21 and 60. RESULTS: The histological analyses showed the following results. Postoperative day three: presence of inflammatory infiltrate, erythrocytes and proliferating fibroblasts in T, C - and C + samples. Day seven: extensive bone neoformation in groups T and C + , and beginning of alpha-TCP resorption by phagocytic cells. Days 14 and 21: osteoblastic activity in the three types of cavities. Day 60: In all samples, neoformed bone similar to surrounding bone. Moderate interruption on the ostectomized cortical bone. CONCLUSIONS: Bone neoformation is seen seven days after implantation of alpha-TCP and autogenous bone. Comparison of C - with T and C + samples showed that repair is faster in implanted cavities; on day 60, control groups presented almost complete bone repair. Alpha-TCP cement presents biocompatibility and osteotransductivity, besides stability, but 60 days after surgery the cavities were not closed. PMID- 20579395 TI - MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation. AB - BACKGROUND: Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of miR-200c has been shown to be associated with upregulating the expression of E-cadherin, a gene known to be involved in pancreatic cancer behavior. However, the significance of miR-200c in pancreatic cancer is unknown. METHODS: In the present study, we investigated the relationship between E cadherin and miR-200c expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of miR-200c on the proliferation and invasion of pancreatic cancer cells. RESULTS: We found that patients with high levels of miR 200c expression had significantly better survival rates than those with low levels of miR-200c expression. We also found a remarkably strong correlation between the levels of miR-200c and E-cadherin expression. CONCLUSIONS: These data indicate that miR-200c may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer. PMID- 20579396 TI - Fathead minnow steroidogenesis: in silico analyses reveals tradeoffs between nominal target efficacy and robustness to cross-talk. AB - BACKGROUND: Interpreting proteomic and genomic data is a major challenge in predictive ecotoxicology that can be addressed by a systems biology approach. Mathematical modeling provides an organizational platform to consolidate protein dynamics with possible genomic regulation. Here, a model of ovarian steroidogenesis in the fathead minnow, Pimephales promelas, (FHM) is developed to evaluate possible transcriptional regulation of steroid production observed in microarray studies. RESULTS: The model was developed from literature sources, integrating key signaling components (G-protein and PKA activation) with their ensuing effect on steroid production. The model properly predicted trajectory behavior of estradiol and testosterone when fish were exposed to fadrozole, a specific aromatase inhibitor, but failed to predict the steroid hormone behavior occurring one week post-exposure as well as the increase in steroid levels when the stressor was removed. In vivo microarray data implicated three modes of regulation which may account for over-production of steroids during a depuration phase (when the stressor is removed): P450 enzyme up-regulation, inhibin down regulation, and luteinizing hormone receptor up-regulation. Simulation studies and sensitivity analysis were used to evaluate each case as possible source of compensation to endocrine stress. CONCLUSIONS: Simulation studies of the testosterone and estradiol response to regulation observed in microarray data supported the hypothesis that the FHM steroidogenesis network compensated for endocrine stress by modulating the sensitivity of the ovarian network to global cues coming from the hypothalamus and pituitary. Model predictions of luteinizing hormone receptor regulation were consistent with depuration and in vitro data. These results challenge the traditional approach to network elucidation in systems biology. Generally, the most sensitive interactions in a network are targeted for further elucidation but microarray evidence shows that homeostatic regulation of the steroidogenic network is likely maintained by a mildly sensitive interaction. We hypothesize that effective network elucidation must consider both the sensitivity of the target as well as the target's robustness to biological noise (in this case, to cross-talk) when identifying possible points of regulation. PMID- 20579397 TI - Maternal feeding practices, child eating behaviour and body mass index in preschool-aged children: a prospective analysis. AB - BACKGROUND: Previous research has found associations between parental feeding practices and children's eating behaviour and weight status. Prospective research is needed to elucidate these relationships. METHODS: One hundred and fifty-six mothers of 2- to 4-year-old children completed questionnaires including measures of maternal feeding practices (pressure to eat, restriction, monitoring and modelling of healthy eating), child eating behaviour (food responsiveness, food fussiness and interest in food), and mother reported child height and weight. The questionnaire was repeated 12 months later. Regression analyses were used to find longitudinal associations between maternal feeding practices, child eating behaviour and child body mass index (BMI). RESULTS: Modelling of healthy eating predicted lower child food fussiness and higher interest in food one year later, and pressure to eat predicted lower child interest in food. Restriction did not predict changes in child eating behaviour. Maternal feeding practices did not prospectively predict child food responsiveness or child BMI. CONCLUSION: Maternal feeding practices appear to influence young children's eating behaviour but not weight status in the short term. PMID- 20579398 TI - A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women. AB - BACKGROUND: A number of health benefits including improvements in acid/base balance, bone metabolism, and cardiovascular risk factors have been attributed to the intake of magnesium rich alkaline mineral water. This study was designed to investigate the effects of the regular consumption of magnesium bicarbonate supplemented spring water on pH, biochemical parameters of bone metabolism, lipid profile and blood pressure in postmenopausal women. FINDINGS: In this double blind, placebo-controlled, parallel-group, study, 67 postmenopausal women were randomised to receive between 1500 mL and 1800 mL daily of magnesium bicarbonate supplemented spring water (650 mg/L bicarbonate, 120 mg/L magnesium, pH 8.3-8.5) (supplemented water group) or spring water without supplements (control water group) over 84 days. Over this period biomarkers of bone turnover (serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, osteocalcin, urinary telopeptides and hydroxyproline), serum lipids (total cholesterol, HDL cholesterol, LDL-cholesterol and triglycerides), venous and urinary pH were measured together with measurements of standard biochemistry, haematology and urine examinations.Serum magnesium concentrations and urinary pH in subjects consuming the magnesium bicarbonate supplemented water increased significantly at Day 84 compared to subjects consuming the spring water control (magnesium - p = 0.03; pH - p = 0.018). The consumption of spring water led to a trend for an increase in parathyroid hormone (PTH) concentrations while the PTH concentrations remained stable with the intake of the supplemented spring water. However there were no significant effects of magnesium bicarbonate supplementation in changes to biomarkers of bone mineral metabolism (n-telopeptides, hydroxyproline, osteocalcin and 1,25-dihydroxyvitamin D) or serum lipids or blood pressure in postmenopausal women from Day 0 to Day 84. CONCLUSIONS: Short term regular ingestion of magnesium bicarbonate supplemented water provides a source of orally available magnesium. Long term clinical studies are required to investigate any health benefits. TRIAL REGISTRATION: ACTRN12609000863235. PMID- 20579402 TI - Fermented wheat aleurone induces enzymes involved in detoxification of carcinogens and in antioxidative defence in human colon cells. AB - Dietary fibre is fermented by the human gut flora resulting mainly in the formation of SCFA, for example, acetate, propionate and butyrate. SCFA, in particular butyrate, may be important for secondary cancer prevention by inducing apoptosis and inhibiting cell growth of cancer cells, thereby inhibiting the promotion and/or progression of cancer. Furthermore, SCFA could also act on primary cancer prevention by activation of detoxifying and antioxidative enzymes. We investigated the effects of fermented wheat aleurone on the expression of genes involved in stress response and toxicity, activity of drug-metabolising enzymes and anti-genotoxic potential. Aleurone was digested and fermented in vitro to obtain samples that reflect the content of the colon. HT29 cells and colon epithelial stripes were incubated with the resulting fermentation supernatant fractions (fs) and effects on mRNA expression of CAT, GSTP1 and SULT2B1 and enzyme activity of glutathione S-transferase (GST) and catalase (CAT) were measured. Fermented aleurone was also used to study the protection against H2O2-induced DNA damage in HT29 cells. The fs of aleurone significantly induced the mRNA expression of CAT, GSTP1 and SULT2B1 (HT29) and GSTP1 (epithelial stripes), respectively. The enzyme activities of GST (HT29) and CAT (HT29, epithelial stripes) were also unambiguously increased (1.4- to 3.7-fold) by the fs of aleurone. DNA damage induced by H2O2 was significantly reduced by the fs of aleurone after 48 h, whereupon no difference was observed compared with the faeces control. In conclusion, fermented aleurone is able to act on primary prevention by inducing mRNA expression and the activity of enzymes involved in detoxification of carcinogens and antioxidative defence. PMID- 20579400 TI - The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells. AB - INTRODUCTION: Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT. METHODS: The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes. RESULTS: mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-beta estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect. CONCLUSIONS: Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells. PMID- 20579399 TI - Impact of promoting longer-lasting insecticide treatment of bed nets upon malaria transmission in a rural Tanzanian setting with pre-existing high coverage of untreated nets. AB - BACKGROUND: The communities of Namawala and Idete villages in southern Tanzania experienced extremely high malaria transmission in the 1990s. By 2001-03, following high usage rates (75% of all age groups) of untreated bed nets, a 4.2 fold reduction in malaria transmission intensity was achieved. Since 2006, a national-scale programme has promoted the use of longer-lasting insecticide treatment kits (consisting of an insecticide plus binder) co-packaged with all bed nets manufactured in the country. METHODS: The entomological inoculation rate (EIR) was estimated through monthly surveys in 72 houses randomly selected in each of the two villages. Mosquitoes were caught using CDC light traps placed beside occupied bed nets between January and December 2008 (n = 1,648 trap nights). Sub-samples of mosquitoes were taken from each trap to determine parity status, sporozoite infection and Anopheles gambiae complex sibling species identity. RESULTS: Compared with a historical mean EIR of approximately 1400 infectious bites/person/year (ib/p/y) in 1990-94; the 2008 estimate of 81 ib/p/y represents an 18-fold reduction for an unprotected person without a net. The combined impact of longer-lasting insecticide treatments as well as high bed net coverage was associated with a 4.6-fold reduction in EIR, on top of the impact from the use of untreated nets alone. The scale-up of bed nets and subsequent insecticidal treatment has reduced the density of the anthropophagic, endophagic primary vector species, Anopheles gambiae sensu stricto, by 79%. In contrast, the reduction in density of the zoophagic, exophagic sibling species Anopheles arabiensis was only 38%. CONCLUSION: Insecticide treatment of nets reduced the intensity of malaria transmission in addition to that achieved by the untreated nets alone. Impacts were most pronounced against the highly anthropophagic, endophagic primary vector, leading to a shift in the sibling species composition of the A. gambiae complex. PMID- 20579404 TI - Ability of a high-total antioxidant capacity diet to increase stool weight and bowel antioxidant status in human subjects. AB - There is limited knowledge about the possible effect of unabsorbed dietary antioxidants that reach the large intestine on bowel habits. The aim of the present study was to investigate whether a dietary recommendation directed to increase diet total antioxidant capacity (TAC) is able to affect gut function in human subjects. In this cross-over intervention, nineteen subjects followed a high-TAC (HT) and a low-TAC (LT) diet for 2 weeks, which were comparable for energy, macronutrient, total dietary fibre and alcohol contents. At the end of each intervention period, the 48 h stool output was recorded. In the faecal samples obtained from a subset of nine subjects, moisture, pH, ammonia content, Lactobacillus and Bifidobacterium counts, faecal water antioxidants and genotoxicity were measured. A 3 d weighed food record was used to assess the diet composition during HT and LT diet intake. Significant increases in the intake of TAC, vitamins E and C and phenolic compounds were observed during the HT diet intake. The higher intake of antioxidants led to increased 48 h stool output (324 (SD 38) g in HT v. 218 (SD 22) g in LT), and to higher TAC and total phenolic concentrations in faecal water. No significant variation in the other measured parameters was observed between the diets. In conclusion, a diet selected to raise the intake of dietary antioxidants is able to increase stool bulk and antioxidant content of faeces. PMID- 20579403 TI - Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress. AB - The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17beta-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner. PMID- 20579405 TI - Effects of low-fat dairy consumption on markers of low-grade systemic inflammation and endothelial function in overweight and obese subjects: an intervention study. AB - Although increased concentrations of plasma inflammatory markers are not one of the criteria to diagnose the metabolic syndrome, low-grade systemic inflammation is receiving large attention as a metabolic syndrome component and cardiovascular risk factor. As several epidemiological studies have suggested a negative relationship between low-fat dairy consumption and the metabolic syndrome, we decided to investigate the effects of low-fat dairy consumption on inflammatory markers and adhesion molecules in overweight and obese subjects in an intervention study. Thirty-five healthy subjects (BMI>27 kg/m2) consumed, in a random order, low-fat dairy products (500 ml low-fat milk and 150 g low-fat yogurt) or carbohydrate-rich control products (600 ml fruit juice and three fruit biscuits) daily for 8 weeks. Plasma concentrations of TNF-alpha were decreased by 0.16 (SD 0.50) pg/ml (P = 0.070), and soluble TNF-alpha receptor-1 (s-TNFR-1) was increased by 110.0 (SD 338.4) pg/ml (P = 0.062) after the low-fat dairy period than after the control period. s-TNFR-2 was increased by 227.0 (SD 449.0) pg/ml (P = 0.020) by the dairy intervention. As a result, the TNF-alpha index, defined as the TNF-alpha:s-TNFR-2 ratio, was decreased by 0.000053 (SD 0.00012) (P = 0.015) after the dairy diet consumption. Low-fat dairy consumption had no effect on IL-6, monocyte chemoattractant protein-1, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 concentrations. The present results indicate that in overweight and obese subjects, low-fat dairy consumption for 8 weeks may increase concentrations of s-TNFR compared with carbohydrate-rich product consumption, but that it has no effects on other markers of chronic inflammation and endothelial function. PMID- 20579406 TI - Dietary patterns and colorectal cancer in a Japanese population: the Fukuoka Colorectal Cancer Study. AB - Few studies have addressed the relation between dietary patterns and colorectal cancer in Japan. We investigated dietary patterns in relation to colorectal cancer risk in a community-based case-control study. The association with dietary patterns was also examined for different sites of colorectal cancer. Data were derived from the Fukuoka Colorectal Cancer Study, including 800 cases and 775 controls interviewed from September 2000 to December 2003. The cases were admitted to one of the participating hospitals for the first surgical treatment during this period. We identified dietary patterns using principal component analysis of intakes of twenty-nine items of food groups and specific foods. Quartile categories of each dietary pattern were used, and non-dietary lifestyle factors and total energy intake were adjusted for in the analysis. We identified three dietary patterns: prudent, high-fat and light-meal patterns. The prudent dietary pattern characterised by high intakes of vegetables, fruits, seafoods and soya foods showed a nearly significant protective association with the overall risk of colorectal cancer (trend P = 0.054), and it was statistically significantly related to a decreased risk of distal colon cancer (trend P = 0.002), but not to that of either proximal colon or rectal cancer. The high-fat and light-meal dietary patterns were not materially related to the overall or site-specific risk of colorectal cancer. In summary, a prudent dietary pattern was associated with a decreased risk of colorectal cancer, especially with that of distal colon cancer, in a fairly large case-control study in Japan. PMID- 20579407 TI - Dietary strategies of immunomodulation in infants at risk for celiac disease. AB - Celiac disease is an inflammatory disorder of the small intestine, triggered by the ingestion of gluten proteins contained in wheat, barley or rye, in genetically susceptible individuals. This disorder is considered to be mainly mediated by cellular immunity and restricted to the human leucocyte antigen-DQ presentation of gluten-derived toxic peptides to T-cells. Moreover, the involvement of innate immunity has been recently demonstrated to be necessary also for the development of intestinal tissue damage. Genetic susceptibility accounts for an uncertain proportion of the disease risk and gluten introduction works as the precipitating factor. However, currently, the research interest is also focused on environmental factors and gene-environment interactions, especially during the first months of life, which might help explain the onset of the disease. Infectious and dietary factors that could modulate the immune response orientating it either towards tolerance or intolerance/autoimmunity are the focus of primary attention. A significant number of studies have looked into the protective effect of breast-feeding against the disease. It is generally accepted that breast-feeding during the introduction of dietary gluten and increasing the duration of breast-feeding are associated with reduced risk of developing celiac disease. However, it is still not fully established whether breast-feeding truly protects with permanent tolerance acquisition or only reduces the symptoms and delays the diagnosis. Moreover, the timing and dose of gluten introduction also seem to be relevant and long-term prospective cohort studies are being carried out in order to elucidate its role in celiac disease development. PMID- 20579408 TI - Zinc, metallothioneins and immunosenescence. AB - Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. The nutritional factor, zinc, may remodel these changes with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by in vitro and in vivo studies. The intracellular zinc homeostasis is regulated by buffering metallothioneins (MT) and zinc transporters (ZnT and ZIP families) that mediate the intracellular zinc signalling assigning to zinc a role of 'second messenger'. In ageing, the intracellular zinc homeostasis is altered, because high MT are unable to release zinc and some zinc transporters deputed to zinc influx (ZIP family) are defective leading to low intracellular zinc content for the immune efficiency. Physiological zinc supplementation in the elderly improves these functions. However, the choice of old subjects for zinc supplementation has to be performed in relation to the specific genetic background of MT and IL-6, because the latter is involved both in MTmRNA and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (C-carriers) in the IL-6-174G/C locus display high IL-6, low intracellular zinc content, impaired innate immunity and enhanced MT. Old subjects carrying GC and CC genotypes (C+carriers) display satisfactory intracellular zinc content, adequate innate immunity and are more prone to reach longevity. Zinc supplementation in old C-carriers restores natural killer cell cytotoxicity and zinc status. The genetic variations of the IL-6 174G/C locus when associated with those of the MT1A+647A/C locus are useful tools for the choice of old people for zinc supplementation. PMID- 20579409 TI - In vitro competitive binding index using fluorochrome-labelled spermatozoa for predicting bull fertility. AB - This work evaluated if an in vitro test, with the combined power of the statistical evaluation of spermatozoa and zona pellucida (ZP) competitive binding ability and a rapid method for accessory sperm counts, could predict the bull fertility. Ten Holstein Friesian bulls of known field fertility (five of high and five of low fertility) were selected. An in vitro heterospermic insemination approach, based on differential staining, was tested on 45 possible pairs of bulls (two batches per bull). Motility and quality (abnormalities and membrane status) seminal characteristics and estimated relative conception rates (ERCR) highlighted only one association between membrane integrity and ERCR (p = 0.007). Differences in ZP binding allowed us to rank bulls into two categories based on low and high binding ability. For eight bulls, this classification reflected the ERCR. Differences between batches were reported for two bulls, in which the effect of heterospermic insemination (the number of sperm binding to ZP from different bulls not in a 1:1 ratio) showed a significant bull-related effect (p < 0.001) in the first batch and no effect (p > 0.05) in the second batch for both bulls. Reduction of the number of oocytes per assay from 25 to 5 had no effect (p > 0.5) on the bulls' ranking. Our results suggest that in vitro competitive binding is a promising approach for estimating bull fertility and support concepts for further implementation, e.g. drastic reduction of oocyte number in a single pair assay and larger scale testing for batches. PMID- 20579410 TI - Effect of donor cell age on development of ovine nuclear transfer embryos in vitro. AB - The effects of the age of cell donor animal on in vitro development of ovine nuclear transfer (NT) embryos were investigated. Somatic donor cells were obtained from two different sources: (1) adult cells (adult fibroblast cells; AFC and adult cumulus cells; ACC); and (2) fetal fibroblasts (40-day-old; FFC-40 and 65-day-old; FFC-65). The fibroblast cell lines were used for NT procedures within 4-13 subpassages. While the cumulus cells were used as non-cultured (fresh) cells. The in vitro matured abattoir-derived oocytes were considered as recipients. No differences in the rates of fusion (75.7, 77.7, 76.3 and 86.7%) and cleavage (80.1, 84.3, 77.8 and 74%) were detected among couplets reconstructed with FFC-40, FFC-65, AFC and ACC, respectively. Blastocyst formation rate of those oocytes reconstructed with FFC-40 was higher (18%; p < 0.001) than those reconstructed with FFC-65 (13%) and AFC (10.9) and comparable with those reconstructed with ACC (17.5%). When the effect of passage number was analysed within groups (FFC-40, FFC-65 and AFC) there were no significant differences in fusion, cleavage and blastocyst rates between reconstructed oocytes. The present study demonstrates that the fetal and adult fibroblasts as well as fresh cumulus cells are comparable in their ability to attain cell fusion and embryonic cleavage. Moreover, the blastocyst formation rate is influenced by the age of the donor animal and the fresh cumulus cells have similar remodelling potential to that of fetal fibroblasts in term of blastocyst formation rate. PMID- 20579411 TI - Epidemiology and burden of rhinitis and rhinoconjunctivitis in 9- to 11-year-old children. AB - BACKGROUND: Rhinoconjunctivitis (RC) is regarded as the most common chronic disease of childhood; however, the currently available epidemiological studies on prevalence, burden, and risk factors of RC are insufficient. This analysis aimed to investigate potential risk factors, symptom frequency, and burden of RC. METHODS: Using the International Study of Asthma and Allergies in Childhood Phase II questionnaires, 6963 elementary school children aged 9-11 years were surveyed in five different city centers of Turkey. All participants were skin-prick tested with common aeroallergens. RESULTS: The prevalence of ever rhinitis, physician diagnosed rhinitis, current rhinitis, and current RC were 51.6, 31.0, 43.5, and 23.1%, respectively; 19.8% of children with RC symptoms were atopic to at least one allergen. Among students with RC symptoms, 42.2, 23.9, 35.8, and 28.2% reported moderate-severe interference of daily activities, at least 1 day of absence from school, visit to a health care professional, and any drug usage for rhinitis, respectively. Nasal decongestants and oral antihistamines were the most frequently used treatment. Approximately 70% of RC patients reported perennial symptoms and 42.8% were classified as mild to intermittent. Multivariate logistic regression analysis revealed family history of asthma and/or allergic rhinitis (odds ratio [OR] = 1.863; confidence interval, [CI] = 1.583-2.191; p < 0.001), living in a house with mold and dampness in the 1st year of life (OR = 1.651; CI = 1.356-2.01; p < 0.001), maternal smoking in pregnancy (OR = 1.425; CI = 1.089 1.864; p = 0.011), low monthly income (OR = 1.685; CI = 1.422-1.998; p = 0.001), current wheezing (OR = 2.543; CI = 2.151-3.006; p = 0.001), and current atopic eczema (OR = 2.503; CI = 1.96-3.196; p = 0.001) as significant risk factors for current RC. CONCLUSION: Along with the high prevalence of RC in childhood, underdiagnosis and undertreatment of the disease are also frequent. The socioeconomic burden of the disease can be reduced by increasing awareness and proper diagnosis/treatment. PMID- 20579412 TI - Efficient and rapid labeling of transplanted cell populations with superparamagnetic iron oxide nanoparticles using cell surface chemical biotinylation for in vivo monitoring by MRI. AB - Determination of the dynamics of specific cell populations in vivo is essential for the development of cell-based therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by gradient-echo and T(2)-weighted MRI techniques. In this study, cancer cells were chemically tagged with biotin and then magnetically labeled with anti-biotin SPIOs. No significant detrimental effects on cell viability or death were observed following cell biotinylation. SPIO labeled cells exhibited signal loss compared to non-SPIO-labeled cells by MRI in vitro. Consistent with the in vitro MRI data, signal attenuation was observed in vivo from SPIO-labeled cells injected into the muscle of the hind legs, or implanted subcutaneously into the flanks of mice, correlating with iron detection by histochemical and X-ray fluorescence (XRF) methods. To further validate this approach, human mesenchymal stem cells (hMSCs) were also employed. Chemical biotinylation and SPIO labeling of hMSCs were confirmed by fluorescence microscopy and flow cytometry. The procedure did not affect proliferation and multipotentiality, or lead to increased cell death. The SPIO-labeled hMSCs were shown to exhibit MRI signal reduction in vitro and was detectable in an in vivo model. In this study, we demonstrate a rapid, robust, and generic methodology that may be a useful and practical adjuvant to existing methods of cell labeling for in vivo monitoring by MRI. Further, we have shown the first application of XRF to provide iron maps to validate MRI data in SPIO-labeled cell tracking studies. PMID- 20579421 TI - Who will teach the next generation of dental hygienists? PMID- 20579422 TI - Legislative initiatives of the developing advanced dental hygiene practitioner. AB - PURPOSE: Today there is a heightened awareness to address access issues and unmet oral needs. The current private practice system of delivering oral health care is failing many Americans. Healthcare advocates and policy makers are taking a greater interest in addressing access problems and have begun to explore new approaches to eliminate oral health care disparities. One solution is the introduction of a new member of the dental team, which is creating a power paradigm shift within the dental profession. As the Advanced Dental Hygiene Practitioner (ADHP) becomes a reality it will be necessary to advocate for change in state dental practice acts to allow this new provider access to populations that are currently unserved or underserved. The National Call to Action to Promote Oral Health report that was published in 2003 called for flexibility in licensure laws that would permit alternative models of delivery of oral healthcare services to vulnerable populations. The American Dental Hygienists' Association responded to the Call to Action by proposing a mid-level provider, the ADHP. Six years later extensive work has led to curricula and one program that accepted applicants for the fall of 2009. This short report will outline steps necessary for changing the practice act along with an example of one state's experience at planning and implementing creative solutions to increase access and eliminate disparities in oral healthcare in a socially responsible and cost-effective approach. PMID- 20579423 TI - The dental water jet: a historical review of the literature. AB - PURPOSE: The objective of this paper is to provide a broad overview of the predominant findings from research published on pulsating dental water jets over the last 45 years. METHOD: The author performed a computerized MEDLINE search covering the years from 1962 to 2009, with 1962 chosen since it was the year the first dental water jet was introduced. Key words included "oral irrigator" and "oral irrigation." All past and current studies were reviewed and those that reflected original research were included. The article is not intended to provide an exhaustive detailed article review, but rather a broad review of predominant findings on currently available traditional pulsating dental water jets with no novelty features. The author makes no attempt to statistically analyze any of the data. Information reported in the article comes from the original investigator analysis and interpretation. RESULTS: The dental water jet is supported by a well established body of evidence demonstrating the ability to remove plaque, reduce periodontal pathogens, gingivitis, bleeding and inflammatory mediators. CONCLUSION: The dental water jet is a viable tool for reducing bleeding and gingivitis in a wide variety of patients. Due to the extensive body of knowledge on this product, a meta-analysis or systematic review is warranted. Additional research is recommended to confirm plaque biofilm removal, its effectiveness in comparison to flossing and efficacy on patients with special oral or systemic health needs. PMID- 20579424 TI - The role of dental hygiene in caries management: a new paradigm. AB - PURPOSE: Dental caries is the most common disease of children and remains a significant oral health problem worldwide for both children and adults. The traditional paradigm of treating dental caries solely by "drilling and filling," brushing and flossing and lowering sugar intake has evolved. Current science in the management of dental caries suggests a clear focus on the reduction of responsible infectious agents, remineralization of non-cavitated lesions and minimally invasive restorative approaches whenever possible. The paradigm shift is away from a purely surgical approach toward more preventive and curative clinical protocols. This paper provides a review of this caries management methodology and explores the role of the dental hygienist in this paradigm change. PMID- 20579425 TI - Effectiveness of multimedia instruction in health professions education compared to traditional instruction. AB - PURPOSE: It is the challenge of many health care educators to find epistemological means to create learning environments that promote critical thinking, decision making and transfer of knowledge from didactic to clinical settings in order to enhance the knowledge, skills and performance of health care students. In addition, due to a rapidly changing health care environment, health professions education has been plagued with increasing quantities of complex information with waning numbers of faculty members. Investigating pedagogical strategies that address these issues is essential. Implementing carefully designed multimedia instruction (MMI) may be part of the solution. This literature review will present research regarding the effectiveness of MMI in health care education compared to traditional pedagogies. Two specific domains emerged from the literature: types of learning with MMI and the instructional design of multimedia learning environments. Regardless of the outcomes of the study, each researcher favorably described the value of MMI in health care education, citing a need for further research before universal implementation of this technology is placed in the curriculum. PMID- 20579426 TI - An oral health survey of the Lumbee tribe in southeastern North Carolina. AB - PURPOSE: The Lumbee tribe, North Carolina's largest American Indian tribe, is located in Robeson County, where there is an access to dental care crisis. There is a high incidence of systemic diseases, including coronary heart disease (CHD) and diabetes. The tribe also has a higher rate of adverse pregnancy outcomes compared to Caucasian populations. There is little information available regarding the oral health of this population. The aim of this study was to evaluate access to dental care issues, oral health knowledge and oral health related quality of life of the Lumbee tribe. METHODS: A self-administered survey was developed to assess factors influencing access to dental care, oral health knowledge and oral health-related quality of life. The survey was administered to a convenience sample of 118 Lumbee Indians at the Lumbee Homecoming Festival in Pembroke, NC. RESULTS: Barriers to accessing dental care included being unable to leave work to find a dentist and cost of dental services. Many believed that it is natural to lose teeth as one ages. There was low oral health knowledge regarding oral and systemic health. Oral Health-related quality of life was affected. There was an association between poor access to dental care and poor oral health-related quality of life. CONCLUSION: Lumbee Indians reported barriers to accessing dental care. There was a significant relationship between difficulty accessing dental care and poor oral health-related quality of life. PMID- 20579427 TI - Bisphenol A blood and saliva levels prior to and after dental sealant placement in adults. AB - PURPOSE: This study examined the effects of a widely used (Delton Pit & Fissure Sealant - Light Cure Opaque, DENTSPLY Professional, York, PA) pit and fissure sealant material on bisphenol A (BPA) levels in blood and saliva, among both low and high-dose groups over time. METHODS: A convenience sample of 30 adults from the Old Dominion University population were randomly and evenly divided into 2 independent variable groups: a low-dose group (1 occlusal sealant application) and high-dose group (4 occlusal sealant applications). A 2 group, time series design was used to examine the presence and concentration of BPA in serum and saliva after sealant placement. Differences comparing low-dose and high-dose groups were examined 1 hour prior (baseline), 1 hour post, 3 hours post and 24 hours after sealant placement, as measured by a direct-competitive BPA Enzyme Linked ImmunoSorbent Assay (ELISA). Hypothesized outcomes were evaluated by applying a parametric, 2 way ANOVA for repeated measures technique to data on the 30 participants ranging in age from 18 to 40 years, and were of mixed gender and ethnicity. RESULTS: BPA was detected in the saliva of all participants prior to sealant placement and ranged from 0.07 to 6.00 ng/ml at baseline. Salivary BPA concentration levels peaked over a 3 hour period following sealant placement and returned to baseline levels within 24 hours. BPA was significantly elevated at all post-sealant placement time periods for both the low-dose (1 occlusal sealant application) and high-dose (4 occlusal sealant applications) groups with peak levels of 3.98 ng/ml and 9.08 ng/ml, respectively. The blood serum did not contain BPA at any point in this investigation. CONCLUSIONS: Exposure to BPA from sources other than dental resins contributes to salivary baseline concentration levels and indicates environmental exposure and use of products containing BPA. Use of specific molecular formulations of dental sealant material determines the release of BPA, therefore, dental sealant materials should be reviewed independently when questioning the release of BPA from dental sealants. In addition, dosage amounts of the dental sealant material used in this study do not influence the serum concentration levels of BPA. Further research is needed to examine the cumulative estrogenic effects of BPA from dental sealants. PMID- 20579428 TI - Anxiolytic intervention preference of dental practitioners in the Savannah, Chatham County area: a pilot study. AB - PURPOSE: The purpose of this study was to identify preferred anxiolytic interventions (AI) employed by dental practitioners in the Savannah, Chatham County area. METHODS: A questionnaire was developed to test dental practitioner preferences of 11 AIs shown to reduce anxiety in dental patients. The sample consisted of dental hygienists, dental assistants and dentists, randomly selected via the telephone book. A total of 305 surveys were distributed. Prior to voluntary completion of the questionnaire, respondents received oral and written instructions regarding the purpose of the study. RESULTS: A 43% return rate (n=131) was achieved. Results from analysis with the Median and Kruskal-Wallis tests suggested that the most commonly used AI was ambient background music (n=109, 83.2%). The second most commonly used AI was having literature available for patients to read (n=99, 75.6%), followed by providing a way for the patient to inform their provider of their anxiety (n=88, 67.2%), the use of pharmaceutical agents (n=79, 60.3%) and decorating the walls (n=68, 51.9%). CONCLUSION: It is important for dental professionals to employ interventions and management techniques that may reduce dental anxiety. PMID- 20579431 TI - Essential criteria for manuscript review. PMID- 20579432 TI - Animal models of substance abuse and addiction: implications for science, animal welfare, and society. AB - Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models. PMID- 20579433 TI - Effects of murine norovirus infection on a mouse model of diet-induced obesity and insulin resistance. AB - Murine norovirus (MNV) is prevalent in SPF mouse facilities in the United States, and we currently lack sufficient data to determine whether it should be eliminated. It is generally accepted that the virus does not cause clinical symptoms in immuno-competent mice. However, we previously reported that MNV infection alters the phenotype of a mouse model of bacteria-induced inflammatory bowel disease in part through its effects on dendritic cells. The tropism of MNV toward macrophages and dendritic cells makes MNV a potential intercurrent variable in murine models of macrophage-driven inflammatory diseases, such as obesity, insulin resistance, and atherosclerosis. Therefore, we determined whether MNV infection altered obesity and insulin resistance phenotypes in C57BL/6 mice, a widely used model of diet-induced obesity. We found that MNV did not alter weight gain, food intake, and glucose metabolism in this model, but it did induce subtle changes in lymphoid tissue. Further studies using other models of metabolic diseases are needed to provide additional information on the potential role this 'subclinical' virus might have on disease progression in mouse models of inflammatory diseases. PMID- 20579435 TI - Etiopathogenesis of mandibulofacial and maxillofacial abscesses in mice. AB - The etiologic agent of mandibulofacial and maxillofacial abscesses in mice is reportedly coagulase-positive Staphylococcus aureus. Although suggested to be through the oral cavity, the exact route of entry has not been documented. Among the clinical cases of mandibulofacial and maxillofacial abscess we report here, each case that was cultured yielded coagulase-positive S. aureus. Histologically, all of the abscesses examined were directly associated with intralesional hair shafts, both vibrissae and pelage, that were introduced into the submucosa via the maxillary or mandibular molar gingival sulci. Grossly, a variable amount of hair was imbedded in the lingual, buccal, or mesial gingival sulci of the maxillary or mandibular molars or both. Computed tomography revealed that the presence of the hair resulted in inflammation and resorption of alveolar bone. With these findings, we propose that mandibulofacial and maxillofacial abscesses are induced by the mastication and fragmentation of hair ingested during the barbering process. From the resulting foreign body periodontitis, abscess formation originates at the maxillary lingual, buccal, or mesial gingival sulci, resulting in infection of the maxillary molar tooth roots with swelling or rupture through the skin inferior to the eye, or at the mandibular lingual, buccal, and or mesial gingival sulci, resulting in infection of the mandibular molar tooth roots and osteomyelitis with drainage through the skin of the ventral mandible. PMID- 20579434 TI - Male CD81 knockout genotype disrupts Mendelian distribution of offspring. AB - CD81 is an integral membrane protein in the tetraspanin superfamily that serves as an adaptor protein. CD81 is also a maternally imprinted gene that is found in a regulated cluster of genes on mouse chromosome 7. Among offspring produced from heterozygous breeding pairs, CD81(null/null) mice grew at the same rate as CD81(+/+) and CD81(+/null) mice. Because of an inhibition in sperm-egg fusion, CD81(null/null) female mice are much less fertile than CD81(+/+) and CD81(+/null) mice. However, no published study has detailed the effect of the male CD81 genotype on the genotype and sex distribution of offspring. We set up breeding pairs of heterozygotic (C.129-Cd81(tm1) N7) female mice and male mice with CD81(+/null), CD81(+/+), or CD81(null/null) genotypes. The survival and development of CD81(+/null), CD81(+/+), and CD81(null/null) offspring were monitored and compared. Compared with those of heterozygous male breeders, CD81(null/null) pups were born at a less-than-expected ratio from CD81(null/null) males. Sex distribution did not differ among pups sired by CD81(null/null) compared with CD81(+/null) mice. The data suggest that the effect of the CD81(null/null) paternal genotype on offspring is manifested early in development or in utero. PMID- 20579436 TI - Cellular compensatory mechanisms in the CNS of dysmyelinated rats. AB - Loss or absolute lack of myelin in the CNS results in remarkable compensation at the cellular level. In this study on the natural progression of neuropathology in the CNS in 2 related but distinct long-lived dysmyelinated rats, total lack of myelin was associated with remarkable glial cell proliferation and ineffective myelinating activity throughout life in Long Evans Bouncer (LE-bo) rats; conversely, in Long Evans Shaker (LES) rats, futile myelinating activity ceased when rats were advanced in age. Progressively severe astrogliosis separates individual axons from each other and coincides with widespread, abundant axonal sprouting throughout the life in both rat strains. Severely dysmyelinated Long Evans rats can serve as excellent models to elucidate the cellular and molecular mechanisms of neuroglial compensation to lack or loss of myelin in vivo and to study axonal plasticity in the adult demyelinated CNS. PMID- 20579437 TI - Development and characterization of a rat model of nonpenetrating liver trauma. AB - The aim of this study was to develop and characterize a rodent model of liver trauma suitable for preclinical evaluation of new treatments and diagnostic technologies. Liver trauma was created by dropping a steel cylinder through a plastic tube onto the abdomen of supine, anesthetized rats. Internal hemorrhage in the absence of liver trauma was simulated by instilling fresh blood into the peritoneum. Platelet counts were elevated significantly after liver trauma but not simulated hemorrhage. Liver trauma and simulated internal hemorrhage both increased blood levels of the factor growth-regulated oncogene-Kupffer cell. Transcription of plasminogen activator inhibitor 1, heat shock protein 70, and suppressor of cytokine syntheses 3 was increased 77-, 22-, and 27-fold, respectively, 2 h after liver trauma but was unaltered by simulated internal hemorrhage. Levels returned to pretrauma levels by 24 h after trauma. Transcript levels for hypoxia-inducible transcription factor 1alpha were increased 2.8-fold at 24 h but not 2 h after trauma and were not affected by simulated hemorrhage. Production of heat shock protein 70 and inducible nitric oxide synthase in liver was limited to a penumbra surrounding areas of necrosis associated with trauma. The rat model described produces lesions similar to those that occur in humans after blunt trauma. PMID- 20579438 TI - Mapping the anatomy of respiratory syncytial virus infection of the upper airways in chinchillas (Chinchilla lanigera). AB - Although most viral infections of the upper respiratory tract can predispose to bacterial otitis media, human respiratory syncytial virus (HRSV) is the predominant viral copathogen of this highly prevalent pediatric polymicrobial disease. Rigorous study of the specific mechanisms by which HRSV predisposes to otitis media has been hindered by lack of a relevant animal model. We recently reported that the chinchilla, the preferred rodent host for studying otitis media, is semipermissive for upper-airway HRSV infection. In the current study, we defined the anatomy and kinetics of HRSV infection and spread in the upper airway of chinchilla hosts. Chinchillas were challenged intranasally with a fluorescent-protein-expressing HRSV. Upper-airway tissues were recovered at multiple time points after viral challenge and examined by confocal microscopy and immunohistochemistry. HRSV replication was observed from the rostral- to caudalmost regions of the nasal cavity as well as throughout the Eustachian tube in a time-dependent manner. Although fluorescence was not observed and virus was not detected in nasopharyngeal lavage fluids 14 d after infection, the latest time point examined in this study, occasional clusters of immunopositive cells were present, suggesting that the nasal cavity may serve as a reservoir for HRSV. These data provide important new information concerning the time course of HRSV infection of the uppermost airway and suggest that chinchillas may be useful for modeling the HRSV-induced changes that predispose to secondary bacterial infection. PMID- 20579440 TI - Finite element analysis of the human mandible to assess the effect of removing an impacted third molar. AB - BACKGROUND AND AIM: Finite element analysis (FEA) was used to generate 3 dimensional models of a human mandible with impacted third molars. The aim was to analyze the effects of removing various amounts of bone around an impacted mandibular third molar and to predict the possibility of iatrogenic fracture. MATERIALS AND METHODS: Data were acquired from cone beam computed tomography (CBCT) scans of a patient using numerically calculated mechanical parameters. Virtual surgery was then performed on the mandibular models, and standardized chewing forces were applied to the resulting simulations. RESULTS: The modelling showed that the highest stress during normal clenching occurred if the surgical procedure involved the external oblique ridge. The peak stress occurred at the site of removal of the third molar, during contralateral loading of the mandible. DISCUSSION: Use of CBCT allowed production of high-quality models of an individual patient and simulation of various surgical scenarios. FEA identified the accumulation of stress and strain at specific parts of the mandible and predicted the responses of bone to mechanical activity. FEA could prove useful to dental practitioners in the future to predict the likelihood of iatrogenic fracture of the jaws after surgical removal of mandibular bone, such as occurs when the third molar is removed. This may allow dentists to change their approach to tooth removal in certain cases. PMID- 20579441 TI - Models for interprofessional practice: innovative collaboration between nursing and dentistry. PMID- 20579439 TI - Comparison of lactate, base excess, bicarbonate, and pH as predictors of mortality after severe trauma in rhesus macaques (Macaca mulatta). AB - Social group housing of rhesus macaques at biomedical facilities is advocated to improve the psychologic wellbeing of these intelligent and social animals. An unintended outcome of social housing in this species is increased intraspecific aggression resulting in cases of severe multiple trauma and posttraumatic shock. The metabolic correlates of oxygen debt are likely important quantifiers of the severity of posttraumatic shock and may serve as useful guides in the treatment of these cases. The purpose of this retrospective study was to evaluate venous blood lactate, base excess, bicarbonate, and pH as predictors of mortality. These 4 variables were assessed in 84 monkeys with severe traumatic injury and shock. Data were available from blood samples collected prior to resuscitation therapy and the day after resuscitation therapy. The pre- and postresuscitation therapy levels of the variables then were tested for association with 6-d survival. When measured prior to resuscitation therapy, all variables were strongly correlated with each other and had a statistically significant association with survival. No single variable had both strong specificity and high sensitivity when measured prior to resuscitation therapy. Survival analysis showed that as the number of categorical indicators of acidosis increased, 6-d survival decreased. Analysis of the 4 variables after resuscitation therapy indicated that lactate was the only variable significantly associated with survival in our study. PMID- 20579442 TI - A diagnostic puzzle in a case featuring gross gingival enlargement. Acute myelocytic leukemia. PMID- 20579443 TI - Lemierre syndrome from an odontogenic source: a review for dentists. AB - Lemierre syndrome, which can result from a recent oropharyngeal or odontogenic infection, is characterized by clinical or radiographic signs of thrombosis of the internal jugular vein, distant infected emboli and the presence of anaerobic pathogens, usually Fusobacterium necrophorum. The septic emboli resulting from the infected thrombophlebitis of the internal jugular vein give the syndrome its constellation of central nervous system, pulmonary and many other manifestations including septic shock. This condition was so rare that, historically, it became known as the "forgotten disease," but an increasing frequency of reports indicates that Lemierre syndrome may not be so uncommon. PMID- 20579444 TI - Clinical teaching in the undergraduate clinic--more difficult than it looks. PMID- 20579445 TI - Developmental disturbance of an unerupted permanent incisor due to trauma to its predecessor. AB - Developmental disturbances of permanent teeth can result from trauma to primary teeth because of the proximity of the root of the primary teeth to their permanent successors. We describe the case of a 14-month-old boy who was referred to the baby clinic of the School of Dentistry, Universidad Estadual Paulista, Aracatuba, Brazil, after sustaining a severe trauma that led to intrusion of the right primary central incisor. Radiographic examination 4 years after the trauma showed a developing morphological change in the germ of the permanent successor. On eruption of the permanent central incisor, a crown malformation along with enamel hypoplasia was observed. We conclude that radiographic follow-up is indicated after trauma to monitor possible sequelae in the permanent successors even before their eruption PMID- 20579446 TI - Is routine radiography for a new patient considered overtreatment? PMID- 20579447 TI - Prevention: dentistry's legacy for the future. PMID- 20579448 TI - Is there a "safety zone" in the mandibular premolar region where damage to the mental nerve can be avoided if periapical extrusion occurs? PMID- 20579449 TI - Why do some people get dizzy in the examination chair? PMID- 20579450 TI - Volunteerism: an opportunity to give back. PMID- 20579451 TI - Improvement in the oral health of Canadians. PMID- 20579452 TI - Epigenetics: new explanations for old problems? PMID- 20579453 TI - Coming out of the cold and stepping into the light: human adaptation in high latitude environments. PMID- 20579454 TI - The Arctic Human Health Expert Group. PMID- 20579455 TI - Restoring Aboriginal culture through community-based type 2 diabetes screening. PMID- 20579456 TI - Incomplete development of the nail of the hallux in the newborn. AB - Between March and October 2008, the nails of 541 (252 females, 289 males) consecutively born neonates with an average age of 3.2 days were examined in the Neonatology Unit. Of these newborns with nail disorders, 36 were re-examined after a period that ranged from seven days to six months. The most frequent nail alteration was the incomplete development of the hallux nail, which was triangular - sometimes trapezoidal - shaped. This alteration, which had been previously reported in the literature as congenital hypertrophy of the lateral folds of the hallux, spontaneously regressed within one to three months in the infants re-examined. There was no associated inflammation or onychocryptosis at any time. The apparent hypertrophy of the nail folds seemed to be secondary to the lack of pressure of the nail lamina. PMID- 20579457 TI - A rare multisystem disorder: Goltz syndrome - case report and brief overview. AB - Focal dermal hypoplasia, also known popularly as Goltz syndrome, is a multisystem disorder characterized by linear or reticulate atrophic macules with fat herniation that is associated with various cutaneous and extracutaneous anomalies. We present a case of a patient with Goltz syndrome who exhibits a classical presentation, associated with exopthalmos major and malrotation of the gut. A brief overview of the syndrome is also presented in an attempt to incorporate all associated anomalies reported so far. PMID- 20579458 TI - Symptomatic zinc deficiency in a full-term breast-fed infant. AB - A nine-month-old female infant presented with an eruption over her face, perineal region, and upper and lower limbs. She had sparse hair growth and diarrhea. Clinical features and investigations were suggestive of hypozincemia. Therapy with zinc and weaning from breastfeeding led to resolution of the condition, confirming a diagnosis of hypozincemia type-II. Recently, a mutation in the zinc transporter gene SLC30A2 (ZnT-2), identified in the mothers of infants suffering from this disorder, is implicated as the cause. This report highlights the occurrence of hypozincemia among a population at risk, consisting of infants who are exclusively breast-fed for a prolonged period. PMID- 20579459 TI - A case of desmoplastic leiomyosarcoma: a rare variant of cutaneous leiomyosarcoma. AB - Desmoplastic leiomyosarcoma is a rare histologic variant of cutaneous leiomyosarcoma seen more commonly in men in their 50s and 60s. This neoplasm typically presents as a solitary, enlarging red-pink nodule or plaque on the extensor surfaces of lower extremities. Its unusual histology mimics other cutaneous desmoplastic lesions and the knowledge of this entity and use of an appropriate immunohistochemical panel is essential to arrive at the correct diagnosis. We report a rare case of desmoplastic leiomyosarcoma of the left flank in a 66-year-old male who presented with itching and pain in a long-standing skin lesion. Histopathology showed the presence of individual and small aggregates of spindle to pleomorphic cells with numerous mitoses in a densely fibrotic stroma. Immunohistochemically, the cells were positive for smooth muscle actin, heavy chain myosin, and desmin, confirming their smooth muscle origin. A diagnosis of desmoplastic leiomyosarcoma was made. We discuss the case with a short review of the literature. PMID- 20579460 TI - Granuloma faciale with disseminated extra facial lesions. AB - Granuloma faciale (GF) is a rare cutaneous disorder categorized as a localized form of small vessel vasculitis. Clinically, it manifests as single or multiple, well-demarcated, red-brown plaques, papules and nodules, nearly always confined to the face. Herein, we report a 39-year-old man with multiple red-brown, infiltrated plaques on his face and extrafacial lesions on the back, shoulders, and both arms. Skin biopsy revealed typical histopathological findings of GF. The patient failed to respond to pulsed dye laser, but intralesional triamcinolone combined with cryotherapy led to an acceptable response. PMID- 20579461 TI - Subcutaneous midline suprasternal mass in a ten-month-old girl. AB - A ten-month-old girl presented to our clinic with a progressively enlarging congenital mass at the midline suprasternal location. Histopathologic examination revealed a benign cyst with stratified squamous keratinized epithelium with numerous eccrine glands in the sinus wall. The diagnosis was compatible with dermoid cyst. Dermoid cysts of the trunk are rare lesions, but a midline location is characteristic for these congenital masses. A dermoid cyst should be high on the list of differential diagnoses given a unilocular midline cyst in a neonate. PMID- 20579462 TI - Extensive segmental acanthosis nigricans form of epidermal nevus. AB - Eight cases of the acanthosis nigricans form of epidermal nevus have been described in literature. The present case is impressive and has an extensive segmental distribution. Although etiological factors, such as mutations in the FGFR3 gene, are becoming recognized, treatment options remain limited. We present a case of a 14-year-old male with multiple hyperpigmented, hyperkeratotic plaques on the upper body, axillae, and groin with a segmental distribution following Blaschko lines. Histopathological investigation showed aspects of both acanthosis nigricans and epidermal nevus. So far, screening has not revealed any internal abnormalities. As previous cases show a clear association with internal diseases, repetitive screening for internal diseases and syndromes is suggested in the case of the acanthosis nigricans form of epidermal nevus. Treatment of the condition remains a challenge. PMID- 20579463 TI - Extensive hypertrophic lichen planus in an HIV positive patient. AB - Individuals who are infected with Human Immunodeficiency Virus (HIV) suffer from numerous dermatoses. These disorders are often more severe than those observed in non HIV-infected persons afflicted with the same diseases. Lichen planus (LP) is a chronic inflammatory papulosquamous skin disorder. Herein, the diagnosis and treatment of a 40-year-old HIV+ Kenyan man afflicted with hypertrophic lichen planus (HLP) is described. In this case, lesions of HLP were widely distributed across the trunk and extremities, having become of such thickness on the dorsal surfaces of the hands and fingers as to make normal use of hands impossible. A significant distinguishing feature of this patient is prior history of tuberculosis, which is a known trigger for lichenoid skin lesions. PMID- 20579464 TI - Cell phone allergic contact dermatitis: case report and review. AB - The combination of increased cell phone ownership and unlimited usage plans has led to a situation in which metal cell phone parts may come into contact with the cell phone user's ear and face for prolonged periods of time. Thus, it is not surprising that recent reports of facial allergic contact dermatitis to cell phone metals have begun to emerge. In this paper we present a case of allergic contact dermatitis to cell phone metal and review all other reports on the subject. We also discuss what the implications of cell phone contact dermatitis are for dermatologists and patients. PMID- 20579465 TI - Fractionated electroblation - using electro surgery for cutaneous redundancies and bulky flaps. AB - Various techniques have been advocated for standing cone removal. A fine tipped electrosurgery epilating tip can be used to burn into the subcutaneous tissue in a grid-like pattern. This causes significant dermal tissue contraction and spares the overlying tissue. We have termed this technique, "fractionated electroblation." PMID- 20579466 TI - Brown plaques on the lower back. AB - A 12-year-old girl presented with a 2-year history of a 10 cm area of asymptomatic brown coalescent plaques of coalescent, linearly arranged papules on the lower back. No other physical or systemic abnormality was detected. Routine laboratory investigations, including thyroid function tests, were normal. The histopathological examination revealed hyperkeratosis, papillomatosis, and elongated rete ridges in the epidermis. On special staining (Alcian blue), mucin deposition was seen in the papillary dermis. The remaining dermis was normal. A diagnosis of Mucinous Nevus was made. PMID- 20579467 TI - A man with infiltrated and indurated plaque on the forehead. AB - Osteoma cutis, a rare benign condition characterized by the presence of osseous nodules are composed of lamellar bone with osteocytes in the center and osteoclasts in the external area, in the reticular layer of the skin. Osteoma cutis can be either primary, arising de novo in healthy skin, or secondary, developing in association with pre-existing neoplastic or inflammatory skin lesions. We present a 25-year-old man with plaque-like osteoma cutis. PMID- 20579468 TI - Two adjacent nodules on the leg. AB - Poroma is a rare benign neoplasm (derived from the intraepidermal part of the eccrine or apocrine duct), which may clinically mimic malignant tumors such as (amelanotic) malignant melanoma and porocarcinoma. Histopathological examination is the key to the correct diagnosis, which is illustrated in the present case, in which a pigmented basal cell carcinoma and a poroma are in close proximity to each other. Despite a clinical differential diagnosis of melanoma, histopathology showed the typical characteristics of a poroma, a rare but much more favorable tumor. Histopathological features of poroma are discussed. PMID- 20579469 TI - Generalized skin drug eruption to natalizumab in a patient with multiple sclerosis. AB - We report a generalized skin eruption in a young man being treated with natalizumab, a new drug used in patients with multiple sclerosis. PMID- 20579470 TI - Long-term management of erythrodermic psoriasis with anti-TNF agents. AB - Erythrodermic psoriasis is a chronic condition that is difficult to treat. Biological agents offer a new alternative, but there are no controlled trials to support their use; there are a few reports of patients treated with these agents, but often only with short term results. We report a 68-year-old man with erythrodermic psoriasis and ankylosing spondylitis, treated with infliximab for 48 weeks and then low-dose etanercept monotherapy for 34 additional months. Excellent results were obtained for both conditions without significant side effects. We think etanercept can be a good therapeutic option for long-term control of erythrodermic psoriasis. PMID- 20579471 TI - Focal skin toxicity related to methotrexate sparing psoriatic plaques. AB - Methotrexate (MTX) is an antimetabolite and antifolate drug used in the treatment of cancer and autoimmune diseases. MTX inhibits DNA synthesis by competitive inhibition of dihydrofolate reductase in immunologically active cells. It also decreases inflammation by other mechanisms. Cutaneous toxicity is usually dose related and generally occurs when recommended guidelines are ignored or there is a decrease in renal excretion. Self-medication is a problem with unknown prevalence. Signs of MTX toxicity include bone marrow suppression, hepatotoxicity, and mucocutaneous toxicity. Painful erosions of psoriatic plaques and, less commonly, erosions in patients without psoriasis have been reported as an early sign of MTX toxicity. To our knowledge, this is the first case of skin toxicity related to MTX that affected the normal skin and spared the psoriatic plaques. PMID- 20579472 TI - [Screening diabetic retinopathy using a telediagnosis system. Results of the upper Rhine survey]. AB - INTRODUCTION: The aim of this study was to present the results of diabetic retinopathy screening using a nonmydriatic fundus camera in the upper Rhine (France). METHOD: The screening period took place from September 2004 to December 2007. Patients came to three referring medical centers (Altkirch, Mulhouse, Thann) and all had three fundus photographs on both eyes without pupillary dilatation. The data were stored on a website. The photographs were then analyzed by the team of experts from the Department of Ophthalmology of the Mulhouse General Hospital. The results were sent to the general practitioner with treatment guidelines. The campaign was evaluated at the end of the screening period using a questionnaire. RESULTS: In this study, 1050 diabetics patients were screened: 18% had diabetic retinopathy; of these 1.5% had proliferative or serious nonproliferative diabetic retinopathies and 74.2% mild nonproliferative forms. The mean value of hemoglobin A1C was 9.3% (+/-2.55), the patients' mean age of patients was 61.5 (+/-14.3) years, and the mean onset of diabetes was 16.6 (+/-7.9) years before screening. After screening, 70% of the patients consulted an ophthalmologist. Ninety percent of the referent practitioners received the results of the screening. CONCLUSION: The diabetic retinopathy screening campaign in the upper Rhine provided a real benefit in terms of public health and prevention of diabetic retinal complications. PMID- 20579473 TI - [Intravitreal bevacizumab in the treatment of neovascular glaucoma]. AB - PURPOSE: To report the effect of an intravitreal injection of 1.25 mg (0.05 ml) of bevacizumab (IVB) as symptomatic treatment for neovascular glaucoma. PATIENTS AND METHOD: This prospective study included 13 eyes of 12 patients presenting neovascular glaucoma, in two cases secondary to ischemic central retinal vein occlusion and, in ten cases, to proliferative diabetic retinopathy. Each patient received an intravitreal injection of 1.25 mg (0.05 ml) of bevacizumab, in combination with other procedures such as panretinal photocoagulation to treat retinal ischemia and transscleral cyclocryoapplication as glaucoma treatment. Their mean age was 58 years (range, 35-75 years). The mean intraocular pressure (IOP) was 40 mmHg+/-10 mmHg. The mean follow-up was 6 months. RESULTS: IVB resulted in a marked regression of anterior segment neovascularization and relief of symptoms within 48 h. IOP decreased substantially in eight eyes; in four eyes, adjuvant cyclocryoapplication was necessary. The last eye was affected by a retinal detachment 1 month after IVB. No side effects were observed. DISCUSSION: We observed that the intravitreal injection of bevacizumab enabled the total regression of iris and angle neovascularization but had only a partial action on intraocular hypertension. CONCLUSION: Intravitreal injection of 1.25 mg (0.05 ml) of bevacizumab contributes to a better management of neovascular glaucoma. PMID- 20579474 TI - [Prognosis factors in diabetic macular edema: an OCT study]. AB - INTRODUCTION: Macular edema is responsible for a significant degree of visual loss in diabetic patients. The prognosis factors in diabetic macular edema are varied and better documented by optical coherence tomography (OCT). We describe the patterns of diabetic macular edema demonstrated by OCT and correlate them with visual acuity. PATIENTS AND METHOD: A prospective study of 297 eyes with diabetic macular edema was conducted. An OTI/OCT exam was done for all eyes. The Fisher test was used to search for a correlation between visual acuity and each feature of diabetic macular edema (macular thickness, cystoid macular edema, central cyst, tractional component, and serous retinal detachment). RESULTS: Visual acuity varied from 1.3 log MAR to 0 log MAR. The mean visual acuity was 0.51 log MAR. The presence of central cyst on OCT scan was significantly associated with worse vision (p<0.0001). Increased retinal thickness in all patterns was significantly correlated with worse visual acuity (p<0.0001). The OCT patterns containing a tractional component and serous retinal detachment were also associated with visual loss (p<10(-6)). CONCLUSION: OCT is a very useful objective tool to describe, classify, and manage diabetic macular edema. It provides a better analysis of different prognosis factors and therefore can assist in determining a more suitable treatment for diabetic macular edema. PMID- 20579475 TI - [Permanent cosmetics and magnetic resonance imaging]. AB - INTRODUCTION: We report a case illustrating the possible relation between permanent cosmetics (tattoos) and magnetic resonance imaging (MRI). OBSERVATION: A 24-year-old woman underwent a permanent cosmetic tattoo (eyeliner) on the four eyelids 5 months before an MRI was performed for headache. After 1 min, the patient reported a burning sensation associated with an eyelid erythema. The MRI examination was interrupted. The burning sensation resolved by the end of the examination and erythema 2 h later. CONCLUSION: Cosmetic tattoo technicians, patients, and MR technologists should be informed of the minor risk associated with the site of the permanent cosmetic tattoo (eyelid, eyebrow). PMID- 20579476 TI - [Macroprolactinoma revealed by an exophthalmos]. AB - With the purpose of illustrating a particular circumstance of giant macroprolactinoma diagnosis, we report the case of a 54-year-old woman who was seen in the Endocrinology department with the suspected diagnosis of hyperthyroidism in presence of unilateral exophthalmos. The patient reported headaches during the last year and secondary amenorrhea since she was 38 years old. The ophthalmologic examination confirmed the unilateral left exophthalmos, which was associated with oculomotor paralysis and vision loss. The computed tomography demonstrated a great mass of the sella extending in all directions and destroying the bone. The hormonal investigation confirmed the diagnosis of prolactinoma, with a level of 8723 ng/ml, and revealed hypopituitarism. The start of bromocriptin treatment was followed by a fall in the prolactin level to less then 200 ng/ml in 1 month. This case is particular regarding the giant macroprolactinoma in a woman discovered by an unusual visual complication. PMID- 20579477 TI - [Eyedrops in children and pregnant or breast-feeding woman: why so many difficulties?]. AB - The use of eye drops in a child or a pregnant or a breast-feeding woman is often difficult, since clearly established license and scientific data are rare. These two difficulties are related. Indeed, clinical research programs exceptionally include children or pregnant/breastfeeding women, except when the product is directly intended for these populations, unusual in ophthalmology. As a consequence, the scientific publications give very little information on the balance between benefit and risk in these patients. Legal authorities therefore cannot base authorization decisions on robust data or on the contrary clearly mention the danger of many ophthalmic solutions. For that reason, the summaries of the characteristics of the product most often include precautionary recommendations, in practice a rejection, even when the empirical clinical practice suggests their possible use. The analysis of these difficulties underlines the importance of conducting clinical trials including this type of patient or, failing that, the necessity of consensus conferences to facilitate physicians' daily medical practice. PMID- 20579478 TI - [Conjunctival Kaposi sarcoma]. AB - Kaposi sarcoma is rare and occurs in four forms (classic, endemic, post transplant and epidemic), which all have the same histological appearance associated with the same viral agent: human herpes virus type 8 (HHV-8). Conjunctival and palpebral locations are, however, rare, and only 30 cases have been described in the literature. We present the case of a 34-year-old woman with conjunctival Kaposi angiosarcoma, with rare bulbar location associated with superior palpebral telangiectases against a rare immunodepression syndrome (common variable immunodeficiency). The treatment consisted of an excision biopsy with an over-and-over suture of a conjunctival rotation flap, combined with anti HHV-8 chemotherapy to effect a regression of the palpebral lesion. However, the reappearance of a conjunctival lesion on the rim of the excision site required local radiotherapy of approximately 30 Gy, with no recurrence after 1 month. PMID- 20579479 TI - [Retinal detachment caused by giant traumatic tear with retinal inversion]. PMID- 20579481 TI - Gel-based immunotest for simultaneous detection of 2,4,6-trichlorophenol and ochratoxin A in red wine. AB - A new rapid method which allows simultaneous one step detection of two analytes of different nature (2,4,6,-trichlorophenol (TCP) and ochratoxin A (OTA)) in red wine was developed. It was based on a column test with three separate immunolayers: two test layers and one control layer. Each layer consisted of sepharose gel with immobilized anti-OTA (OTA test layer), anti-TCP (TCP test layer) or anti-HRP (control layer) antibodies. Analytes bind to the antibodies in the corresponding test layer while sample flows through the column. Then a mixture of OTA-HRP and TCP-HRP in appropriate dilutions was used, followed by the application of chromogenic substrate. Colour development of the test layer occurred when the corresponding analyte was absent in the sample. HRP-conjugates bound to anti-HRP antibody in the control layer independently of presence or absence of analytes and a blue colour developed in the control layer. Cut-off values for both analytes were 2 microg L(-1). The described method was applied to the simultaneous detection of TCP and OTA in wine samples. To screen the analytes in red wine samples, clean-up columns were used for sample pre-treatment in combination with the test column. Results were confirmed by chromatographic methods. PMID- 20579483 TI - Molecularly imprinted polymer solid-phase extraction for detection of zearalenone in cereal sample extracts. AB - The aim of this work was to develop a method for the clean-up and preconcentration of zearalenone from corn and wheat samples employing molecularly imprinted polymer (MIP) as selective sorbent for solid-phase extraction (SPE). Cereal samples were extracted with acetonitrile/water (75:25, v/v) and the extract was diluted with water and applied to an AFFINIMIP ZON MIP-SPE column. The column was then washed to eliminate the interferences and zearalenone was eluted with methanol and quantified using HPLC with fluorescence detection (lambda(exc)=275/lambda(em)=450 nm). The precision and accuracy of the method were satisfactory for both cereals at the different fortification levels tested and it gave recoveries between 82 and 87% (RSDr 2.5-6.2%, n=3) and 86 and 90% (RSDr 0.9-6.8%, n=3) for wheat and maize, respectively. MIP-SPE column capacity was determined to be not less than 6.6 microg of zearalenone and to be at least four times higher than that of immunoaffinity column (IAC). The application of AFFINIMIP ZON molecularly imprinted polymer as a selective sorbent material for detection of zearalenone fulfilled the method performance criteria required by the Commission Regulation (EC) No. 401/2006, demonstrating the suitability of the technique for the control of zearalenone in cereal samples. PMID- 20579482 TI - Color encoded microbeads-based flow cytometric immunoassay for polycyclic aromatic hydrocarbons in food. AB - Food contamination caused by chemical hazards such as persistent organic pollutants (POPs) is a worldwide public health concern and requires continuous monitoring. The chromatography-based analysis methods for POPs are accurate and quite sensitive but they are time-consuming, laborious and expensive. Thus, there is a need for validated simplified screening tools, which are inexpensive, rapid, have automation potential and can detect multiple POPs simultaneously. In this study we developed a flow cytometry-based immunoassay (FCIA) using a color encoded microbeads technology to detect benzo[a]pyrene (BaP) and other polycyclic aromatic hydrocarbons (PAHs) in buffer and food extracts as a starting point for the future development of rapid multiplex assays including other POPs in food, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). A highly sensitive assay for BaP was obtained with an IC(50) of 0.3 microg L(-1) using a monoclonal antibody (Mab22F12) against BaP, similar to the IC(50) of a previously described enzyme-linked immunosorbent assay (ELISA) using the same Mab. Moreover, the FCIA was 8 times more sensitive for BaP compared to a surface plasmon resonance (SPR)-based biosensor immunoassay (BIA) using the same reagents. The selectivity of the FCIAs was tested, with two Mabs against BaP for 25 other PAHs, including two hydroxyl PAH metabolites. Apart from BaP, the FCIAs can detect PAHs such as indenol[1,2,3-cd]pyrene (IP), benz[a]anthracene (BaA), and chrysene (CHR) which are also appointed by the European Food Safety Authority (EFSA) as suitable indicators of PAH contamination in food. The FCIAs results were in agreement with those obtained with gas chromatography-mass spectrometry (GC-MS) for the detection of PAHs in real food samples of smoked carp and wheat flour and has great potential for the future routine application of this assay in a simplex or multiplex format in combination with simplified extraction procedure which are under development. PMID- 20579484 TI - Electronic nose as an innovative tool for the diagnosis of grapevine crown gall. AB - For the first time, a portable electronic nose was used to discriminate between healthy and galled grapevines, experimentally inoculated with two tumourigenic strains of Agrobacterium vitis. The volatile profile of target cutting samples was analysed by headspace solid phase microextraction coupled with gas chromatography-mass spectrometry. Spectra from tumoured samples revealed the presence of styrene which is compatible with decarboxylation of cinnamic acid involved in secondary metabolism of plants. Principal Component Analysis confirmed the difference in volatile profiles of infected vines and their healthy controls. Linear Discriminant Analysis allowed the correct discrimination between healthy and galled grapevines (83.3%, cross-validation). Although a larger number of samples should be analysed to create a more robust model, our results give novel interesting clues to go further with research on the diagnostic potential of this innovative system associated with multi-dimensional chemometric techniques. PMID- 20579485 TI - Towards development of incurred materials for quality assurance purposes in the analysis of food allergens. AB - Food allergy and intolerance became very important problems in food safety and healthcare during the last few decades. Beside the pharmaceutical treatment of the symptoms, effective cure of these illnesses is the avoidance of the problematic food proteins. According to this reason, proper legislation is crucial for protecting sensitive people. In the European Union 14 allergenic components must be labelled which requires introduction of properly validated analytical methods for the appropriate quantification of allergenic proteins. The aim of our work is studying such parameters which may affect the analytical results, therefore have to be taken into account during the validation process. For investigating these issues, an incurred sample matrix was produced, namely a wheat flour based cookie, which contains allergenic proteins (milk or egg) in a dedicated amount. Using these samples the effects of food processing steps and the analytical performance of the applied Enzyme-Linked Immunosorbent Assay (ELISA) methods were studied. A major finding of our work is that heat treatment caused a large-scale decrease in the amount of measurable allergen content of the samples. The background of this phenomenon has not been clarified yet. Besides, the gathered data indicates that the performance of the ELISA method is highly related to the state of the sample matrix. These problems altogether must be taken into consideration for making a proper validation protocol and revealing their background also has a great importance in further evaluation of the analytical methods. PMID- 20579486 TI - Validation of a two-plate microbiological method for screening antibiotic residues in shrimp tissue. AB - Microbiological inhibition screening tests could play an important role to detect residues of antibiotics in the different animal food products, but very few are available for the aquaculture products in general, and for shrimps in particular. A two-plate microbiological method to screen shrimp for residues of the most commonly used antibiotics has been developed and validated according to criteria derived from the European Commission Decision 2002/657/CE. Bacillus subtilis was used as a sensitive strain to target antibiotics. Culture conditions on Petri plates (pH of medium) were selected to enhance the capacity of antibiotic detection. Antibiotic residues were extracted from shrimps using acetonitrile/acetone (70/30, v/v) before application on Petri plates seeded with B. subtilis. The method was validated using spiked blank tissues as well as antibiotic treated shrimps with enrofloxacin and tetracycline, two antibiotics often found to be used in shrimp production. For tetracyclines and (fluoro)quinolones, the detection capability was below the maximum residue limit (MRL), while it was around the MRL for sulfonamides. The specificity of the microbiological screening was 100% in all cases while the sensitivity and accuracy was 100% in almost all cases. The capacity of the method to detect contaminated samples was confirmed on antibiotic treated shrimps, analyzed in parallel with a confirmatory method (Liquid Chromatography coupled to mass spectrometry (LC-MS)). PMID- 20579487 TI - Glazing of frozen fish: analytical and economic challenges. AB - Adequate glazing (6-10%) of fish fillets prior to frozen storage protects the final product from dehydration, oxidation and quality loss. Excessive glazing (>12%) on the other hand may significantly affect the economic value and end user satisfaction of frozen fish fillets. This paper describes the optimization, validation and application of a gravimetric procedure for the quantification of the ice-glaze content of frozen fish fillets (accredited under ISO 17025). This procedure has been utilized to determine the glazing percentage of multiple batches (n=50) of 11 different fish species sampled from 2005 until 2009. Average glazing percentages were 8.7+/-2.0% for the pooled samples (n=712), and ranged between 6.6+/-2.2% (salmon/cod) and 10.6+/-1.6% (plaice). The lower threshold value of 6% glazing for sufficient protection was violated in only one batch, whereas none of the batches exceeded the 12% excessive glazing threshold. The annual market place value of one %-point glazing is estimated at 1 million Euro in a low to moderate fish consumption market like Belgium. The large variability of glazing, combined with this technology's possible implications with respect to end-product-quality and economic value urges for technology improvement, monitoring and more controlled application of the glazing process in the frozen fish industry. PMID- 20579488 TI - Detection of recombinant bovine somatotropin in milk and effect of industrial processes on its stability. AB - A LC-MS/MS method has been developed for the direct detection of recombinant bovine somatotropin (rbST) in milk and dairy products. The sample preparation protocol is based on a solid phase extraction step followed by precipitation with cold methanol and enzymatic digestion. The analysis is focused on the tryptic N terminal peptide, specific of the recombinant form of the hormone and the detection is performed by LC-ESI(+)-MS/MS. This method has been validated according to the European Union criteria described in the Directive 2002/657/EC. Acceptable performances, with a decision limit (CCalpha) of 1.24 ng mL(-1) and detection capability (CCbeta) of 1.92 ng mL(-1) were obtained. Calculation of repeatability and intermediate reproducibility of the signal at 100 ng mL(-1) lead to relative standard deviations lower than 20%, showing the robustness of the method. Samples subjected to various industrial processes namely, heating, freezing, defatting, pasteurization and spray-drying were then analysed in order to determine the consequences of these treatments on the stability of the hormone. Results showed that temperature related processes, such as pasteurization and spray-drying induce a loss of the hormone up to 95%. PMID- 20579489 TI - Depletion study of PCDD/Fs and dioxin-like PCBs concentrations in contaminated home-produced eggs: preliminary study. AB - Dioxins (PCDD/Fs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. The contamination of food products with dioxins and PCBs is a well studied issue, because food is generally considered the major source of dioxin intake for humans. In Italy, the Regional Monitoring Plan (part of the national residue monitoring plan) used in the field for 2009 has also included the control of environmental pollutants in small egg producers. Following an irregular result, 12 laying hens were transferred into a laboratory controlled environment. Eggs were collected for 60 days and they were weekly analysed for the evaluation of dioxins, dioxin-like PCBs (DL-PCBs), and non dioxin-like PCBs (NDL-PCBs, six congeners) levels. The dioxins and PCBs contents were determined, according to EPA methods, by gas chromatography ic determination coupled with high resolution mass spectrometry (HRGC-HRMS). The content of PCDD/Fs, DL-PCBs and NDL-PCBs was evaluated weekly by mean from week to week. The concentration of dioxins was lower than DL-PCBs (2.5 pg TEQ g(-1) of fat against 4.5 pg TEQ g(-1) of fat), but we observed the same depletion trend for both pollutants. On the opposite, NDL-PCBs had a different course: we noted there was an increase between weeks 6 and 7, but the mean levels remained very low (about 20 ng g(-1) of fat). The dioxins, and sum of dioxin and DL-PCBs concentration were below the fixed European limits (i.e. 3 pg TEQ g(-1) of fat for dioxins and 6 pg TEQ g(-1) of fat for sum of dioxins and DL-PCBs), beginning from the 3rd week of trial. PMID- 20579490 TI - Furan levels in fruit and vegetables juices, nutrition drinks and bakery products. AB - Furan, an oxygen containing monocyclic aromatic hydrocarbon, is considered possibly carcinogenic to humans. In the framework of the EU-project "Role of Genetic and Non-Genetic Mechanisms in Furan Risk", furan levels in food have been collected from the literature. Three food type categories have been selected on the basis of the collected data for sampling and analysis on furan with headspace GC-MS. This paper describes the results for the selected food categories, fruit and vegetables juices, nutrition drinks and bakery products. An attempt has been made to correlate the furan levels with the ingredients of the products. PMID- 20579491 TI - Development of a new analytical method for the determination of sulfites in fresh meats and shrimps by ion-exchange chromatography with conductivity detection. AB - An accurate and reliable analytical method, based on ion chromatography and suppressed conductivity detection, has been developed and validated for the quantitative determination of sulfites in fresh meats and shrimps. The chromatographic separation was accomplished by using an anion-exchange column eluted with sodium carbonate and sodium hydroxide. The optimized step-change elution, followed by column re-equilibration at the initial mobile phase composition, guaranteed a good resolution even toward endogenous interfering peaks, and an excellent retention time repeatability (1.1%, n=6). Good results in terms of sample extract stability, recovery efficiency were achieved with an extraction solvent mixture based on sodium hydroxide, fructose and EDTA. The method validation, performed by an in-house model according to Decision 657/2002/EC and Regulation 882/2004/EC, provided excellent results with respect to linearity (correlation coefficient up to 0.9998), limits of detection and quantification (2.7 and 8.2 mg kg(-1), respectively, expressed as SO(2)), expanded measurement uncertainty (below 10%), recovery values (ranging from 85% to 92%) and repeatability (down to 8%), demonstrating the conformity of the proposed method with the European directives. Finally, by major changes ruggedness studies, the method applicability to the quantitative analysis of cow hamburger, pork and horse sausage, and shrimps was demonstrated. PMID- 20579492 TI - Statistical evaluation of fatty acid profile and cholesterol content in fish (common carp) lipids obtained by different sample preparation procedures. AB - Studies performed on lipid extraction from animal and fish tissues do not provide information on its influence on fatty acid composition of the extracted lipids as well as on cholesterol content. Data presented in this paper indicate the impact of extraction procedures on fatty acid profile of fish lipids extracted by the modified Soxhlet and ASE (accelerated solvent extraction) procedure. Cholesterol was also determined by direct saponification method, too. Student's paired t-test used for comparison of the total fat content in carp fish population obtained by two extraction methods shows that differences between values of the total fat content determined by ASE and modified Soxhlet method are not statistically significant. Values obtained by three different methods (direct saponification, ASE and modified Soxhlet method), used for determination of cholesterol content in carp, were compared by one-way analysis of variance (ANOVA). The obtained results show that modified Soxhlet method gives results which differ significantly from the results obtained by direct saponification and ASE method. However the results obtained by direct saponification and ASE method do not differ significantly from each other. The highest quantities for cholesterol (37.65 to 65.44 mg/100 g) in the analyzed fish muscle were obtained by applying direct saponification method, as less destructive one, followed by ASE (34.16 to 52.60 mg/100 g) and modified Soxhlet extraction method (10.73 to 30.83 mg/100 g). Modified Soxhlet method for extraction of fish lipids gives higher values for n-6 fatty acids than ASE method (t(paired)=3.22 t(c)=2.36), while there is no statistically significant difference in the n-3 content levels between the methods (t(paired)=1.31). The UNSFA/SFA ratio obtained by using modified Soxhlet method is also higher than the ratio obtained using ASE method (t(paired)=4.88 t(c)=2.36). Results of Principal Component Analysis (PCA) showed that the highest positive impact to the second principal component (PC2) is recorded by C18:3 n-3, and C20:3 n-6, being present in a higher amount in the samples treated by the modified Soxhlet extraction, while C22:5 n-3, C20:3 n-3, C22:1 and C20:4, C16 and C18 negatively influence the score values of the PC2, showing significantly increased level in the samples treated by ASE method. Hotelling's paired T-square test used on the first three principal components for confirmation of differences in individual fatty acid content obtained by ASE and Soxhlet method in carp muscle showed statistically significant difference between these two data sets (T(2)=161.308, p<0.001). PMID- 20579493 TI - Characterization of isoflavone composition in soy-based nutritional supplements via ultra performance liquid chromatography. AB - The specific isoflavone composition of nutritional supplements is commonly not labeled, although the stated amounts are strongly dependent on the present isoflavone conjugates. Hence, 11 soy-based dietary supplements were characterized via a newly established ultra performance liquid chromatography (UPLC) method, on both their native conjugated isoflavone spectra, as well as on quantitative amounts derived as total aglycones after enzymatic hydrolysis utilizing Helix pomatia juice. Capitalizing on sub-2 microm particles, the established RP-UPLC technique facilitated efficient chromatographic separation of all 12 soy intrinsic isoflavone forms within 10 min. Derived native isoflavone profiles implied a certain variability, comprising conjugated forms, especially glycosides, as the predominant isoflavonic constituents throughout the majority of supplements, whereas only two samples indicated the more bioavailable free aglycones as prevailing compounds. Moreover, the robust quantification as total aglycones subsequent to enzymatic hydrolysis, unexceptionally yielded negative deviations referring to the labeled specifications, thus implying that stated amounts were typically calculated on basis of the high molecular isoflavone conjugates. Thus, especially in regard to better comparability, regulations concerning an uniform labeling basis are needed. PMID- 20579494 TI - A sensitive method for free amino acids analysis by liquid chromatography with ultraviolet and mass spectrometric detection using precolumn derivatization with diethyl ethoxymethylenemalonate: application to the honey analysis. AB - In case of some foods and drinks, their amino acid content is demonstrated to correlate with the botanical and/or geographical origin of the plant. In present work a method for amino acid analysis in honey was developed and validated. The method consists of sample preparation (including solid phase extraction), derivatization with diethyl ethoxymethylenemalonate and liquid chromatographic analysis. Full separation of 23 amino acids was achieved. All steps were extensively studied and optimized for analytical performance. Although ultraviolet (UV) detection provides sufficient sensitivity for honey analysis, all the steps of the method were designed to be compatible with mass spectrometric (MS) detection. The developed method has been applied to analysis of nearly 200 Estonian honey samples. PMID- 20579495 TI - Determination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry. AB - A confirmatory method for the determination of residues of nine non-steroidal anti-inflammatory drugs and one metabolite in animal muscles has been developed. After enzymatic hydrolysis samples were extracted with acetonitrile and cleaned up using alumina and C(18) SPE cartridges. Liquid chromatography-tandem mass spectrometry was used for the separation and determination of analytes. The method was validated in bovine muscles, according to the Commission Decision 2002/657/EC criteria. Applicability of the method in the analysis of swine, horse and chicken muscles was checked by precision and recovery experiment. The influence of matrix effect on the quantification of non-steroidal anti inflammatory drugs residues was investigated. The method was used for the confirmation of phenylbutazone and oxyphenbutazone in horse muscle sample. PMID- 20579496 TI - Multi-residue determination of seventeen sulfonamides and five tetracyclines in fish tissue using a multi-stage LC-ESI-MS/MS approach based on advanced mass spectrometric techniques. AB - A strategy was newly developed to rapidly screen seventeen sulfonamides and five tetracyclines in a single run from fish tissues using ultra-high performance liquid chromatography (UHPLC) coupled with comprehensive mass spectrometric approaches, including precursor-ion scan and data dependent scan. The product ions for precursor-ion scanning were selected by studying the MS/MS fragmentation of the analytes. All sulfonamides share the same diagnostic product ion at m/z 156 in positive MS/MS scan, while for tetracycline antibiotics the diagnostic product ion was proved to be at m/z 153.8. Further characterization of each compound was performed using a data dependent scan. Separation was performed on a Zorbax Eclipse Plus C18 column with a gradient elution using acetonitrile - 0.1% formic acid mobile phase at a flow rate of 0.1 mL min(-1). This approach has proven to be a powerful, highly selective, and sensitive tool for rapid screening and detection of non-targeted components in fish tissue and requires a minimum sample preparation such as one generic extraction step with MeOH:ACN 50:50 (v/v) acidified with 0.05% formic acid. The method has also been applied successfully to porcine and poultry meat. The validation of such a screening method was performed for the first time according to Commission Decision 2002/657/EC and satisfactory method performance characteristics were achieved. PMID- 20579497 TI - Confirmatory method for the determination of streptomycin in apples by LC-MS/MS. AB - The method was specifically developed for the determination and confirmation of streptomycin in apple samples using the whole mellow apple. The method is simple, rapid, sensitive and was validated for streptomycin in accordance with SANCO/3131/2007. After extraction with phosphate buffer and a pH change, the clean-up was performed by the way of SPE with polymeric phase. The LC-MS/MS analysis was carried out using a HILIC column for the separation of the analytes and a triple quadrupole mass spectrometer in positive ESI mode to measure the transitions of the substances in MRM mode. For the quantification of streptomycin a matrix calibration curve in the linear range of 1.0-20 microg kg(-1) and the internal standard dihydrostreptomycin (10 microg kg(-1)) were used. The calculated validation parameters like the recovery (101-105%) for 2, 5, 10 and 20 microg kg(-1) and the relative standard deviation (RSD, 4.1-11.4%) of the 6 replicates fulfil the requirements of SANCO/3131/2007. The LOQ was determined as 2 microg kg(-1). PMID- 20579498 TI - Validation of an off line solid phase extraction liquid chromatography-tandem mass spectrometry method for the determination of systemic insecticide residues in honey and pollen samples collected in apiaries from NW Spain. AB - The use of pesticides to protect crops against plagues and insects is one of the most important ways to assure agricultural quality and productivity. However, bad application practices may cause the contamination of different environmental compartments and animal species, as a consequence of migration or accumulation of those compounds. Fipronil, imidacloprid and thiametoxam are systemic or systemic like insecticides widely used in maize crops. Their heavy action in the nervous system of target insects also means a high toxicity to non-target pollinator insects such as honey bees which can get in touch with them through pollen and nectar during foraging activities. These insecticides have even been suspected to cause a significant decrease of honeybee colonies that has been observed in many countries since the past decade. Since September 1st 2008, the European Commission set new MRLs in food and feed of plant and animal origin. The pesticides included in this study have MRLs in honey and pollen between 10 and 50 ng g(-1). In the present work, an analytical method was developed with the aim of determining residues of fipronil and some of its metabolites (fipronil sulfone, fipronil sulfide, fipronil desulfinyl and fipronil carboxamide), thiamethoxam and imidacloprid in honey and pollen samples. The extraction optimization was performed using a Doehlert experimental design by studying two factors, the mixture and the ratio of solvents used. Prior to the extraction procedure, raw hive samples containing honey, pollen and wax were centrifuged at 4000 rpm. The upper solid material was removed, and 1 g of the lower phase was mixed with 3 mL of the optimized mixture of methanol/water (10/90). The extract was passed through a florisil cartridge and the target compounds were eluted with methanol and analysed by LC-MS/MS in selective reaction monitoring (SRM) mode. The method was validated according to the guidelines included in the SANCO/10684/2009 document and the ISO 11843 standard for the following parameters: decision limit (CCalpha), detection capability (CCbeta), recovery, repeatability and reproducibility at 0.5, 1 and 1.5 folds the MRLs. Ion suppression/enhancement effects into the ion source were also assessed. The CCbeta values were included between 0.83 and 4.83 ng g(-1), well below the current MRLs. The validated method was applied to the determination of the target pesticides in 91 samples collected in colonies from 73 apiaries of NW Spain (two sampling campaigns during 2008). None of the target insecticides were detected among all the collected samples. PMID- 20579499 TI - Two-dimensional gas chromatographic profiling as a tool for a rapid screening of the changes in volatile composition occurring due to microoxygenation of red wines. AB - Microoxygenation (MOX) is a widely applied technique to deliver continuously trace amounts of oxygen to red wine during vinification and ageing in order to improve color stability and sensory properties. Proven by sensory means, the added oxygen modifies not only tannin structure and color of the wines, but also their composition of volatiles. In this study different microoxygenation treatments prior and after malolactic fermentation were carried out for Pinot noir, Cabernet Sauvignon and Dornfelder wines of the 2007 vintage. Volatile components of subsequent wines were analyzed using headspace-solid phase microextraction coupled to comprehensive two-dimensional gas chromatography quadrupole mass spectrometry (GC x GC-qMS). Quantitative data were retrieved from two-dimensional images obtained from GC x GC chromatograms of volatile compounds applying a software package, which is commonly used in the field of proteomics for two-dimensional electrophoresis gels. This approach revealed a discrimination of the applied treatments by multivariate statistics based on volatiles alone, such as the clear distinction among wines treated before or after malolactic fermentation in case of Cabernet Sauvignon and Dornfelder or the effect of different oxygen doses. Besides the differentiation of MOX treatments from the untreated control, specific varietal and technological effects could be distinguished. The image processing of the GC x GC data offered valuable tools which were able to identify those areas in the 2D images that were most responsible for discrimination among different MOX treatments. Based on the loadings of individual aroma compounds a set of markers for the MOX-induced modifications of volatiles could be suggested. PMID- 20579500 TI - Determination of benzene in different food matrices by distillation and isotope dilution HS-GC/MS. AB - Benzene is classified by the IARC as carcinogenic to humans. Several sources may contribute for the occurrence of benzene in foods, such as, environmental contamination and the reaction of benzoate salts with ascorbic acid (naturally present or added as food additives). Matrix effect on benzene recovery (e.g. in fatty foods) and artefactual benzene formation from benzoate during analysis in the presence of ascorbate are some of the challenges presented when determining benzene in a wide range of foodstuffs. Design of experiment (DOE) was used to determine the most important variables in benzene recovery from headspace GC/MS. Based on the results of the DOE, a versatile method for the extraction of benzene from all kind of food commodities was developed. The method which consisted of distillation and isotope dilution HS-GC/MS was in-house validated. Artefactual benzene was prevented by addition of a borate buffer solution (pH 11) under distillation conditions. The method presented in this study allows the use of a matrix-independent calibration with detection limits below the legal limit established by the European Council for benzene in drinking water (1 microg L( 1)). PMID- 20579501 TI - Development of a stir bar sorptive extraction method coupled to gas chromatography-mass spectrometry for the analysis of volatile compounds in Sherry brandy. AB - Sherry brandy (Jerez, SW, Spain) is a high quality distilled beverage derived from wine. Its perceived quality depends, inter alia, on hundreds of flavour compounds. A Stir Bar Sorptive Extraction (SBSE) method coupled to gas chromatography-mass spectrometry has been developed for the analysis of volatile compounds in Sherry brandy. The optimization of the extraction procedure has been carried out using a statistical approach, based on a factorial design. The best overall analytical conditions obtained were the following: 35 mL of sample, diluted 1:1 with Milli-Q water and extraction at 1100 rpm for 100 min. The method has been successfully validated in a further stage of this work. Several performance characteristics such as calibration, linearity, precision (inter- and intra-assay), detection and quantification limits and recovery were studied. Finally, the method developed has been applied to different Sherry brandies. The results obtained show SBSE to be a suitable technique for the reliable analysis of volatile compounds in brandies. PMID- 20579502 TI - Single-run determination of polybrominated diphenyl ethers (PBDEs) di- to deca brominated in fish meal, fish oil and fish feed by isotope dilution: application of automated sample purification and gas chromatography/ion trap tandem mass spectrometry (GC/ITMS). AB - The present paper describes the application of automated cleanup and fractionation procedures of the Power Prep system (Fluid Management Systems) for the determination of polybrominated diphenyl ethers (PBDEs) in feeding stuffs and fish meal and oil. Gas chromatography (GC) separation followed by ion trap tandem mass spectrometry detection in EI mode (ITMS) allowed the analysis of di- to deca BDEs in the samples matrices used in fish aquaculture. The method developed enabled the determination of 26 native PBDE congeners and 11 (13)C(12)-labelled congeners, including deca-BDE 209, in a single-run analysis, using isotope dilution. The automated cleanup, consisting of a succession of multilayer silica and basic alumina columns previously applied by Wyrzykowska et al. (2009) [28] in combustion flue gas, was successfully applied in our complex matrices. The method allowed an increase in productivity, i.e. lower time was required to process samples, and simultaneous purification of several samples was achieved at a time, reducing analyst dedication and human error input. Average recoveries of 43-96% were obtained. GC/ITMS can overcome the complexity originating from the sample matrix, eliminating matrix effects by tandem MS, to enable the detection of congeners penta- to nona-BDEs where interferent masses were present. The provisional detection limits, estimated in the samples, were 5-30 pg for di-, tri , tetra-, and penta-BDEs, 20-65 pg for hexa-, hepta-, octa- and nona-BDEs, and 105 pg for deca-BDE. Reduction of deca-BDE 209 blank values is of concern to ongoing research. Good accuracy was obtained by application of the whole procedure, representing an efficient, low-cost and fast alternative for routine analyses. PMID- 20579503 TI - Prevalence and treatment of narcissistic personality disorder in the community: a systematic review. AB - BACKGROUND: Few studies have examined the prevalence and treatment of narcissistic personality disorder (NPD). METHOD: We systematically reviewed studies of NPD that used suitable diagnostic methods in adult nonclinical samples and evaluated their strengths and weaknesses. Searches were conducted of MEDLINE (using both MeSH category and free-word search terms), PsycINFO, and PsycLIT for articles in English from January 1980 to August 2008 using the terms Narcissis* and prevalence, of unpublished work identified via contacts with experts in the field, of books on personality disorders, and of reference lists from relevant articles and books. We evaluated articles using a 6-point epidemiologic quality tool that we developed. To determine the most efficacious treatments for NPD without other comorbidities, we performed searches using Narcissis*, pharmacology, clinical pharmacology, therapeutics, and psychotherapy for reports of controlled trials from January 1980 to August 2008. RESULTS: We identified 7 prevalence studies that had used a structured or semistructured interview, 5 of which scored 5/6 using the epidemiologic quality tool. Mean prevalence was 1.06%, and the range was 0% to 6.2%. We found no studies of treatment meeting our inclusion criteria. CONCLUSIONS: There was an overall finding of a low prevalence of NPD in adult nonclinical samples. Changes in the classification system might promote further empirical investigations. PMID- 20579504 TI - A different approach toward screening for bipolar disorder: the prototype matching method. AB - Most screening scales for psychiatric disorders consist of a series of questions about the signs and symptoms of the disorder of interest, and to determine whether a patient screens positive, the scores of the individual items are summed and the total score is compared with an empirically derived threshold. A problem with the score summation approach toward case identification on screening scales is that different studies may find that different thresholds are optimal for distinguishing cases from noncases. An alternative approach toward screening is the prototype matching approach, in which respondents are asked to indicate how well their clinical history matches the described prototype. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we compared the symptom summation and prototype matching approaches toward screening for bipolar disorder in a large sample of psychiatric outpatients. Nine hundred sixty-one psychiatric outpatients were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and completed the Bipolar Spectrum Disorders Scale (BSDS). The BSDS is a unique screening scale consisting of a prototypic description of bipolar disorder. The respondent checks off which items in the prototypic paragraph describes them and also answers a single multiple-choice question at the end of the paragraph asking how well the paragraph describes them. The results of a receiver operating curve analysis found that the score summation and prototype matching approaches toward screening on the BSDS performed equally well. These findings provide preliminary evidence that an alternative approach toward psychiatric screening, the prototype matching approach, is as effective as the traditional score summation method. This raises the intriguing possibility of developing a combined screening scale/educational instrument that can be formatted as a brochure and thus placed in clinicians' waiting rooms, thereby facilitating use of the measure. PMID- 20579505 TI - A clinical comparison of pathologic skin picking and obsessive-compulsive disorder. AB - BACKGROUND: It has been hypothesized that pathologic skin picking (PSP) shares many of the same biological and phenomenological characteristics as obsessive compulsive disorder (OCD). This study sought to examine the clinical similarities between PSP and OCD. METHOD: Demographic and clinical characteristic data were examined in a treatment-seeking sample of 53 PSP (mean age, 34.2 +/- 13.1 years; 86.8% female) and 51 OCD (mean age, 36.5 +/- 11.7 years; 35.3% female) subjects. Psychiatric comorbidity and family history data were also obtained. RESULTS: The PSP subjects were more likely to be female (P < .001), report higher rates of co occurring compulsive nail biting (P < .001), and have a first-degree relative with a grooming disorder (P < .001). The OCD subjects spent significantly more time on their thoughts and behaviors (P < .001) and were more likely to have co occurring body dysmorphic disorder (P = .001). CONCLUSION: Although PSP and OCD share some clinical similarities, important differences exist and cast doubt on the conceptualization of PSP as simply a variant of OCD. PMID- 20579506 TI - Correlates and impact of obsessive-compulsive comorbidity in bipolar disorder. AB - BACKGROUND: Anxiety morbidity in general is frequent and harmful in bipolar disorder. Little is known, however, whether obsessive-compulsive comorbidity entails particular effects. This report aims to evaluate the prevalence and impact of obsessive-compulsive disorder (OCD) comorbidity in a relatively large clinical sample of bipolar disorder, with other lifetime anxiety comorbidities used as a more rigorous control group. METHODS: A cross-sectional study in a consecutive clinical sample, with anxiety comorbidity derived from the intake Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was conducted. Anxiety was assessed with the Hamilton Anxiety Rating Scale. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to assess (hypo)manic and depressive symptoms. The domains of the WHOQOL BREF were used to evaluate quality of life. RESULTS: Lifetime prevalence of OCD comorbidity was 12.4%. No cases of OCD were detected during mania. Compared with subjects with no anxiety comorbidity, those with lifetime OCD were more likely to have a history of suicide attempts, rapid cycling, and alcohol dependence. Patients with OCD had a lower score on all domains of the WHOQOL. Compared with those with other lifetime anxiety disorders, those with OCD had more anxiety, which mediated a lower WHOQOL social domain. CONCLUSIONS: Bipolar disorder patients with obsessive-compulsive comorbidity have a number of indicators of an overall more severe illness. The presence of more anxiety symptoms and a lower social quality of life may be more specific features of the bipolar-OCD comorbidity. PMID- 20579507 TI - Do the obsessive-compulsive symptoms have an effect in schizophrenia? AB - OBJECTIVE: Schizophrenia presents with different symptom domains and functionality during its course. Obsessive-compulsive (OC) symptoms in schizophrenia have many themes to be clarified. Our aim was to compare schizophrenia patients with and without OC symptoms in terms of symptom domains, cognitive functions, and quality of life. METHOD: Sixty-two patients who met schizophrenia diagnosis were assessed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition consecutively over a period of 12 months in the setting of an outpatient clinic at medical university hospital. Yale-Brown Obsessive-Compulsive Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, and neuropsychologic tests were used. Quality of life was assessed with Quality of Life Scale for Patients with Schizophrenia. RESULTS: Obsessive compulsive symptoms along with schizophrenia were present in a considerable number in our sample (35.5%). Level of psychotic symptoms was more severe and quality of life was lower in schizophrenia patients with OC symptoms. A positive correlation was found between obsessions and delusions. Moreover, there was a positive correlation between compulsions and total Scale for the Assessment of Positive Symptoms score and bizarre behaviors subscore. There was no difference between the 2 groups regarding neurocognitive functions. The level of quality of life of schizophrenic patients with OC symptoms was lower. Besides, no correlation was found between OC symptoms and neurocognition and quality of life. CONCLUSIONS: The findings of this study indicate that schizophrenia patients with OC symptoms had severe psychotic symptoms with a distinctive clinical picture including good neurocognition but poor functioning. PMID- 20579508 TI - Self-disorder and subjective dimensions of suicidality in schizophrenia. AB - We studied 25 schizophrenia patients using the Examination of Anomalous Self Experience phenomenological interview framework. In a previous study, this sample was qualitatively interviewed concerning subjective reasons for suicidal ideation. We hypothesized that 2 main identified reasons for suicidality, that is, sense of solitude and inferiority feelings, would be associated with disturbances measured by the Examination of Anomalous Self-Experience scale, that is, disorders of self-awareness and self-presence. The hypothesis was empirically supported. The results shed some additional light on suicidality in schizophrenia: it appears to be partly motivated by a disordered sense of self. These findings, if replicated, may have considerable therapeutic and preventive implications. PMID- 20579510 TI - Extended-release fluvoxamine and improvements in quality of life in patients with obsessive-compulsive disorder. AB - OBJECTIVE: We hypothesized that subjects with obsessive-compulsive disorder (OCD) who received extended-release fluvoxamine (fluvoxamine ER) in a 12-week placebo controlled trial would exhibit improvements in psychosocial domains of health related quality of life (HRQOL) and that additional improvements would occur after a 40-week open-label extension trial. We also hypothesized that greater OCD symptom improvement in the first 12 weeks of treatment would be associated with greater HRQOL improvement after 52 weeks of treatment. METHODS: In the 12-week placebo-controlled trial, subjects were randomized to receive placebo or 100 mg/d of fluvoxamine ER and then titrated in weekly 50 mg increments to a final dose of 100 to 300 mg/d. All subjects enrolled in the 40-week extension trial followed a similar titration, during which they were maintained on their highest well tolerated dose. RESULTS: After 12 weeks of treatment, fluvoxamine ER subjects experienced significantly greater decreases than placebo subjects in Yale-Brown Obsessive-Compulsive Scale scores (P = .001). Both the active drug and placebo groups exhibited significant improvements in psychosocial domains of HRQOL; further improvement occurred after 40 weeks of open-label treatment with active drug. The greater the improvement in OCD severity at 12 weeks, the greater the improvement at 52 weeks in the psychosocial domains (Social Functioning r = 0.39, P = .027; Emotional Problems r = -0.37, P = .037; Mental Health r = -0.49, P = .004). CONCLUSION: Improvement in Yale-Brown Obsessive-Compulsive Scale severity scores during treatment with fluvoxamine ER was associated with improvements in psychosocial aspects of HRQOL that increased over an extended period of treatment. PMID- 20579509 TI - Association among aggressiveness, neurocognitive function, and the Val66Met polymorphism of brain-derived neurotrophic factor gene in male schizophrenic patients. AB - BACKGROUND: The aim of this study was to investigate the association among aggressive behavior, neuropsychological function, and the Val66Met functional polymorphism of brain-derived neurotrophic factor (BDNF) gene in male schizophrenic patients. METHODS: We examined 51 male patients with schizophrenia who had committed homicide (ie, H-SCZ), 50 male patients with schizophrenia who had not committed homicide (ie, NH-SCZ), and 50 healthy male controls. Patients were evaluated using the Positive and Negative Syndrome Scale, Life History of Aggression, and the Overt Aggression Scale. In addition, patients were given neurocognitive function tests, including Korean-Wechsler Adult Intelligence Scale short form, the Korean version of the Rey Memory Test, the Stroop Test, and the Wisconsin Card Sorting Test. The Val66Met polymorphism of the BDNF gene was also genotyped in all schizophrenic patients. RESULTS: We observed no significant difference between patients in the H-SCZ and NH-SCZ groups, with regard to Positive and Negative Syndrome Scale scores. Total Life History of Aggression (P < .01) and Overt Aggression Scale scores for the most severe episode (P < .01) or for the previous month (P < .05) were higher in the H-SCZ group than in the NH SCZ group. There were no significant differences in the genotype distribution or allelic frequency of the Val66Met polymorphism between the schizophrenic groups. In addition, we observed no significant differences between H-SCZ and NH-SCZ groups with regard to performance on neuropsychological tests. The Met allele of the Val66Met polymorphism was associated with poor intelligence quotient, memory quotient), learning, and delayed recall in the H-SCZ group. However, genotype did not seem to influence neurocognitive function in schizophrenic patients who had committed homicide. CONCLUSIONS: The neurocognitive tests used in our study were unable to distinguish between violent and nonviolent schizophrenic patients. Furthermore, the Val66Met polymorphism was not associated with aggressiveness in patients with schizophrenia. PMID- 20579511 TI - The role of gender in single vs married individuals with bipolar disorder. AB - BACKGROUND: Despite the importance of marriage as a source of social support, it has been largely neglected in studies of bipolar disorder; and differential effects on men and women have not been explored. METHODS: Data on episodes of depression, mania, and mixed states were collected for the previous 2 years from a sample of 282 bipolar individuals using the National Institute of Mental Health Life Chart Methodology. RESULTS: Effects unique to women included the following: Bipolar women were significantly more likely to be married. Married women had fewer episodes of depression during the past 2 years than never-married women, and the cumulative severity of depression was lower. There were no differences in diagnostic subtype or age of onset between married and never-married women. Among men, never-married men were more likely to have bipolar I disorder and had an earlier age of onset compared with married men. There were no differences between married and never-married men in frequency, duration, or severity of mood episodes. CONCLUSIONS: Partner selection processes as they relate to bipolar disorder may be different for men and women. The bipolar I diagnostic subtype and early age of onset were associated with a lower likelihood of being married for men, but not for women. Marriage was associated with less depression in women during a 2-year period; but marital status was not associated with disease course differences in men, suggesting that women may be more sensitive to the positive effects of social support available within a stable marital relationship. PMID- 20579512 TI - The affect-regulation function of nonsuicidal self-injury in eating-disordered patients: which affect states are regulated? AB - This study examines the affect regulation function of different types of nonsuicidal self-injury (NSSI) in 177 female eating-disordered inpatients. Almost 45% of the eating-disordered patients displayed at least 1 type of NSSI. Cutting and scratching were the most common forms of NSSI followed by bruising and burning oneself. For all types of NSSI except bruising, the affect regulation function was most strongly endorsed. Affect states reported to precede and follow NSSI were also examined to determine the particular affect states regulated by NSSI. In general, positively valenced low-arousal affect states increased and negatively valenced high-arousal affect states decreased from before to after NSSI. Finally, affective changes associated with NSSI were related to different NSSI characteristics, indicating that the increase in positive affect after NSSI is significantly related to the frequency of NSSI and the numbers of functions reported for NSSI. Theoretical and treatment implications are discussed. PMID- 20579514 TI - Perceived expressed emotion in anorexia nervosa, bulimia nervosa, and binge eating disorder. AB - The aim of this study was to verify the level of expressed emotion (EE) as perceived from patients with an eating disorder (ED). The Italian translation of the Level of Expressed Emotion Scale was administered to 63 female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of anorexia nervosa, bulimia nervosa, and binge-eating disorder and 63 control subjects, according to a case-control procedure. Patients with ED showed higher level of perceived EE than controls, whereas no significant differences were observed when comparing the 3 patient subgroups. The level of perceived EE was found to be independent of age, person who has been most influential in the patient's life, amount of contacts, and duration of treatment. Different associations between eating disorder psychopathology and EE were found, suggesting a close relationship between the emotional response and tolerance of influential person and the dysfunctional attitudes regarding eating, weight, and body shape. PMID- 20579513 TI - Dissociation in eating disorders: relationship between dissociative experiences and binge-eating episodes. AB - OBJECTIVE: Several findings support the hypothesis that there is a relationship between dissociation and eating disorders (EDs). The aims of this study were as follows: (1) to assess whether ED patients show a higher level of dissociation than healthy control (HC) individuals or psychiatric control patients with anxiety and mood disorders and (2) to investigate the effects of dissociation on ED symptoms, specifically binge eating behavior. METHOD: Fifty-four ED patients, 56 anxiety and mood disorders control patients, and 39 HC individuals completed the Eating Disorder Examination Questionnaire and the Dissociation Questionnaire. Each participant was asked about the number of binge eating episodes he or she had experienced in the past 4 weeks. RESULTS: The ED patients had higher levels of dissociation than both the psychiatric control group and the HC group. In the ED group, the number of binge episodes was related to the level of dissociation. DISCUSSION: Dissociative experiences are relevant in EDs, and binge eating is related to dissociation. In patients affected by the core psychopathologic beliefs of EDs (overevaluation of shape and weight), dissociation may allow an individual to initiate binging behavior, thus decreasing self-awareness and negative emotional states, without having to deal with the long-term consequences of their actions. PMID- 20579515 TI - Alterations in QT dispersion in the surface electrocardiogram of female adolescent inpatients diagnosed with bulimia nervosa. AB - Increased QT dispersion (QTd) reflects cardiac autonomic imbalance and indicates elevated risk for cardiac arrhythmias. In the present study, we assessed heart rate, QT and corrected QT intervals, and QTd in 20 acutely ill bulimia nervosa adolescent inpatients on admission and discharge. A significant decrease in QTd was found between admission and discharge (67 +/- 13 milliseconds vs 55 +/- 12 milliseconds, respectively; P = .0005). The decrease in QTd values correlated significantly with the decrease in the frequency of bingeing/purging behaviors (r = 0.51, P = .022). No significant correlations were found between the electrocardiographic indices and other clinical and laboratory measures. The elevated QTd in malnourished bulimia nervosa patients might indicate a cardiac autonomic imbalance that is most likely corrected after symptomatic improvement. PMID- 20579516 TI - Does oppositional defiant disorder have temperament and psychopathological profiles independent of attention deficit/hyperactivity disorder? AB - BACKGROUND: Most studies on temperamental and behavioral/emotional characteristics of oppositional defiant disorder (ODD) did not rule out the effect of comorbid attention-deficit/hyperactivity disorder (ADHD). The main objective of this study was to identify the temperamental and psychopathological patterns of ODD independent of comorbid ADHD. We also aimed to compare the patterns of temperament and psychopathology between ODD with and without ADHD. METHOD: Parents of 2673 students, randomly selected from 19 representative schools in Seoul, Korea, completed the Diagnostic Interview Schedule for Children Version IV. Among 118 children and adolescents with ODD diagnosed by the Diagnostic Interview Schedule for Children Version IV, the parents of 94 subjects (mean age, 10.4 +/- 3.0 years) and the parents of a random sample of 94 age- and gender-matched non-ODD/non-ADHD children and adolescents completed the parent's version of the Child Behavior Checklist (CBCL) and the Junior Temperament and Character Inventory. RESULTS: Subjects with ODD showed temperament and character profiles of high Novelty Seeking, low Self-directedness, and low Cooperativeness, a distinct pattern on the CBCL, and were at increased risk for anxiety and mood disorders compared to the controls after controlling for the effect of comorbid ADHD. The children and adolescents with both ODD and ADHD showed decreased levels of Persistence and Self-directedness and higher scores on 4 subscales of the CBCL (Anxious/Depressed, Attention Problems, Delinquent Behaviors, and Aggressive Behaviors) compared to those with ODD only. CONCLUSIONS: Oppositional defiant disorder is associated with specific temperamental and behavioral/emotional characteristics, independent of ADHD. Moreover, the results of this study support that co-occurring ADHD and ODD have differentially higher levels of behavioral and emotional difficulties. PMID- 20579517 TI - Dissociative psychopathology among opioid use disorder patients: exploring the "chemical dissociation" hypothesis. AB - BACKGROUND: Although early trauma is a well-recognized risk factor for both dissociation and substance abuse, there are inconsistent reports on the association between substance abuse and dissociation. This inconsistency may be resolved by the "chemical dissociation" hypothesis that suggests that some substance abuse patients may not exhibit high levels of dissociation, despite their trauma history, because they may achieve dissociative-like states through chemicals consumption. This article describes 2 studies aimed to (a) assess the incidence of dissociative psychopathology among recovering opioid use disorder (OUD) patients and (b) examine the chemical dissociation hypothesis. METHODS: One hundred forty-nine patients receiving treatment in a heroin recovery program and 46 controls were administered self-report measures of dissociation and childhood maltreatment in study 1. A similar battery and an assessment of addiction severity were completed by 50 methadone maintenance treatment (MMT) patients and 30 detoxified OUD patients in study 2. In addition, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Dissociative Disorders-Revised was administered to a subsample of MMT and detoxified OUD patients. RESULTS: Patients with OUD reported higher levels of child maltreatment and dissociation than controls. Although MMT and detoxified patients did not differ in severity of addiction and child maltreatment, detoxified outpatients had higher levels of dissociation than MMT outpatients: 23% of the detoxified patients and 12% of the MMT patients were diagnosed with a dissociative disorder. CONCLUSIONS: These findings support the chemical dissociation hypothesis of OUD and suggest that detoxification programs should take into consideration the high incidence of comorbid dissociative disorders among their recovering OUD patients. PMID- 20579518 TI - Antisocial personality disorder is on a continuum with psychopathy. AB - BACKGROUND: Antisocial personality disorder (ASPD) and psychopathy are different diagnostic constructs. It is unclear whether they are separate clinical syndromes or whether psychopathy is a severe form of ASPD. METHODS: A representative sample of 496 prisoners in England and Wales was interviewed in the second phase of a survey carried out in 1997 using the Schedules for Clinical Assessment in Neuropsychiatry, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II personality disorders, and the Psychopathy Checklist-Revised. RESULTS: Among those 18 years and older (n = 470), 211 (44.9%) received a diagnosis of ASPD, of whom 67 (31.8%) were classified as psychopaths, indicated by Psychopathy Checklist-Revised scores of 25 and above. Symptoms of ASPD and psychopathy both demonstrated low diagnostic contrast when comparing subgroups of ASPD above and below the cutoff for psychopathy. There were no differences in demography, Axis I comorbidity, and treatment-seeking behavior. Psychopathic individuals with ASPD demonstrated comorbid schizoid and narcissistic personality disorder, more severe conduct disorder and adult antisocial symptoms, and more violent convictions. CONCLUSIONS: Psychopathy and ASPD are not separate diagnostic entities, but psychopathic ASPD is a more severe form than ASPD alone with greater risk of violence. Dimensional scores of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorders (other than ASPD) may be helpful in identifying this specific subgroup. PMID- 20579519 TI - Perceived parental rearing style in childhood: internal structure and concurrent validity on the Egna Minnen Betraffande Uppfostran--Child Version in clinical settings. AB - BACKGROUND: We provide the first validation data of the Spanish version of the Egna Minnen Betraffande Uppfostran--Child Version (EMBU-C) in a clinical context. The EMBU-C is a 41-item self-report questionnaire that assesses perceived parental rearing style in children, comprising 4 subscales (rejection, emotional warmth, control attempts/overprotection, and favoring subjects). METHODS: The test was administered to a clinical sample of 174 Spanish psychiatric outpatients aged 8 to 12. Confirmatory factor analyses were performed, analyzing the children's reports about their parents' rearing style. RESULTS: The results were almost equivalent for father's and mother's ratings. Confirmatory factor analysis yielded an acceptable fit to data of the 3-factor model when removing the items of the favoring subjects scale (root mean squared error of approximation <0.07). Satisfactory internal consistency reliability was obtained for 2 of the 3 scales, rejection and emotional warmth (Cronbach alpha >.73), whereas control attempts scale showed lower values, as in previous studies. The influence of sex (of children and parents) on scale scores was inappreciable and children tended to perceive their parents as progressively less warm as they grew older. As predicted, the scores for rejection and emotional warmth were related to bad relationships with parents, absence of family support, harsh discipline, and lack of parental supervision. CONCLUSIONS: The Spanish version of EMBU-C can be used with psychometric guarantees to identify rearing style in psychiatric outpatients because evidences of quality in this setting match those obtained in community samples. PMID- 20579520 TI - Validation of a Greek adaptation of the 20-item Toronto Alexithymia Scale. AB - BACKGROUND: The purpose of the current investigation was (1) to test whether the 3-factor structure of the 20-item Toronto Alexithymia Scale (TAS-20) corresponding to the theoretical conceptualization of the alexithymia construct could be recovered in a Greek translation of the scale (the TAS-20-G), (2) to assess if a 3-factor structure provides a better fit to the TAS-20-G compared with the recently proposed alternative factor structures, and (3) to evaluate the internal reliability of the TAS-20-G. METHODS: The English version of the TAS-20 was translated into Greek and then back-translated and modified until cross language equivalence was established. The Greek version was then administered to 340 university students. Confirmatory factor analyses were conducted, and 4 different factor structure models were compared. Internal consistency and item-to scale homogeneity of the TAS-20-G and its factor scales were also evaluated. RESULTS: The 3-factor model provided a good fit to the data and proved superior to alternative 1-, 2-, and 4-factor models. Apart from a coefficient alpha below the recommended range for the externally oriented thinking factor, the TAS-20-G and its factor scales demonstrated adequate internal consistency and homogeneity. CONCLUSION: The TAS-20-G is a valid and reliable measure of alexithymia in university students and may be suitable for investigations of alexithymia in other Greek-speaking population samples. PMID- 20579521 TI - The Stayhealthy bioelectrical impedance analyzer predicts body fat in children and adults. AB - Bioelectrical impedance analysis (BIA) is a time-efficient and cost-effective method for estimating body composition. We hypothesized that there would be no significant difference between the Stayhealthy BC1 BIA and the selected reference methods when determining body composition. Thus, the purpose of the present study was to determine the validity of estimating percent body fat (%BF) using the Stayhealthy BIA with its most recently updated algorithms compared to the reference methods of dual-energy x-ray absorptiometry for adults and hydrostatic weighing for children. We measured %BF in 245 adults aged 18 to 80 years and 115 children aged 10 to 17 years. Body fat by BIA was determined using a single 50 kHz frequency handheld impedance device and proprietary software. Agreement between BIA and reference methods was assessed by Bland and Altman plots. Bland and Altman analysis for men, women, and children revealed good agreement between the reference methods and BIA. There was no significant difference by t tests between mean %BF by BIA for men, women, or children when compared to the respective reference method. Significant correlation values between BIA, and reference methods for all men, women, and children were 0.85, 0.88, and 0.79, respectively. Reliability (test-retest) was assessed by intraclass correlation coefficient and coefficient of variation. Intraclass correlation coefficient values were greater than 0.99 (P < .001) for men, women, and children with coefficient of variation values 3.3%, 1.8%, and 1.7%, respectively. The Stayhealthy BIA device demonstrated good agreement between reference methods using Bland and Altman analyses. PMID- 20579522 TI - Satiereal, a Crocus sativus L extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. AB - Snacking is an uncontrolled eating behavior, predisposing weight gain and obesity. It primarily affects the female population and is frequently associated with stress. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. Healthy, mildly overweight women (N = 60) participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Snacking frequency, the main secondary variable, was assessed by daily self-recording of episodes by the subjects in a nutrition diary. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day (n = 31) or a matching placebo (n = 29). Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a significantly greater body weight reduction than placebo after 8 weeks (P < .01). The mean snacking frequency was significantly decreased in the Satiereal group as compared with the placebo group (P < .05). Other anthropometric dimensions and vital signs remained almost unchanged in both groups. No subject withdrawal attributable to a product effect was reported throughout the trial, suggesting a good tolerability to Satiereal. Our results indicate that Satiereal consumption produces a reduction of snacking and creates a satiating effect that could contribute to body weight loss. The combination of an adequate diet with Satiereal supplementation might help subjects engaged in a weight loss program in achieving their objective. PMID- 20579523 TI - Low serum leptin serves as a biomarker of malnutrition in elderly patients. AB - Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P < .001) compared with the malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P < .001), but no significant correlation with C-reactive protein. Sex, weight, and triglyceride were the best predictors of serum leptin (all P < .001). The optimal cutoff value of serum leptin to detect malnutrition was 4.3 ng/mL in men and 25.7 ng/mL in women. Serum leptin may be a good predictor of nutritional status in elderly patients. PMID- 20579524 TI - Improvement of bone formation biomarkers after 1-year consumption with milk fortified with eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and selected vitamins. AB - The hypothesis of this study was that the replacement of regular milk with fortified milk in hyperlipidemic adults for 1 year would improve bone biomarkers. The fortified milk contained eicosapentaenoic acid and docosahexaenoic acid from fish oils, oleic acid, vitamins A, B(6), and E, as well as folic acid. We believe that the fortified milk will improve the blood fatty acid profile and vitamin status in subjects to benefit bone health biomarkers. From the 84 patients who accepted to participate, 11 of these were excluded for the presence of metabolic diseases and 1 was excluded for noncompliance with the protocol. Seventy-two hyperlipidemic patients (35-65 years) were randomly divided between 2 study groups. The supplement group (E; n = 39) consumed 0.5 L/d of fortified milk that contained fish oil, oleic acid, and vitamins. The control group (C; n = 33) consumed 0.5 L/d of semiskimmed milk containing the same amount of total fat. Blood samples were taken at T(0), T(3), T(6), and T(12) months to determine plasma fatty acids, vitamins B(6), E, and 25-hydroxyvitamin D and serum folate, calcium, soluble osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (RANKL), osteocalcin, parathormone, type I collagen carboxy-terminal telopeptide, and malondialdehyde. After 1 year, the E group showed a significant increase in plasma eicosapentaenoic acid (42%), docosahexaenoic acid (60%), vitamin B6 (38%), OPG (18%), RANKL (7%), OPG/RANKL (10%), red blood cell folate (21%), serum folate (53%), calcium (4%), vitamin D (11%), and osteocalcin (22%). Dietary supplementation with the fortified milk drink improved nutritional status and bone formation markers in adult hyperlipidemic patients. PMID- 20579526 TI - Ingestion of potato starch containing esterified phosphorus increases alkaline phosphatase activity in the small intestine in rats. AB - Alkaline phosphatase (ALP) hydrolyzes a variety of monophosphate esters and plays an important role in phosphorus (P) metabolism. Several nutrients in food have been reported to affect intestinal ALP activity in animal models. Previous reports indicated that high levels of P or phosphate in diets decreased intestinal ALP activity in rats. Because potato starch contains considerable amounts of esterified P, unlike other starch-derived plants, we hypothesized that the feeding of potato starch would decrease ALP activity in the intestinal tract. Male Sprague-Dawley rats (7 weeks old) were fed 3 different types of diet containing 60% corn starch or 1 of 2 types of potato starch with different esterified P content for 1 or 5 weeks. Body weight and food intake of each rat were measured every day throughout the experimental periods. At the end of the feeding periods, the small intestine was removed to determine ALP activity in the mucosal tissues. Significant differences were observed in ALP activity in the small intestine between the 2 feeding periods, among the 4 segments of the small intestine, and among the 3 diet groups. Significant positive linear correlations between the amount of P derived from the starch and mucosal ALP activity were obtained in the jejunum and jejunoileum in rats after feeding for 5 weeks. We concluded, contrary to our hypotheses, that the ingestion of potato starch adaptively increases ALP activity in the upper part of the small intestine of growing rats in an esterified P content-dependent manner. PMID- 20579527 TI - The phenolic acids from bacterial degradation of the mangiferin aglycone are quantified in the feces of pigs after oral ingestion of an extract of Cyclopia genistoides (honeybush tea). AB - Polyphenols are cleaved by bacterial enzymes to form phenolic acid metabolites in the colon, where they may exert physiologic effects. For norathyriol, the aglycone of mangiferin, one of the major phenolic compounds present in Cyclopia genistoides (honeybush), a further bacterial degradation is likely; but knowledge of the importance of this metabolic process is very limited. Based on a hypothesized cleavage of the middle ring of norathyriol, this study was designed to determine phenolic cleavage products in the feces of pigs fed an extract of C genistoides. Pigs received 74 mg mangiferin per kilogram of body weight daily for 11 days; feces fractions were collected on day 11 and on the first 2 days after the last intake of extract. Several phenolic acids were detected in the feces samples, including 3-hydroxyphenylacetic acid; 4-hydroxybenzoic acid; 3,4 dihydroxybenzoic acid; 3,4-dihydroxyphenylacetic acid; 2,4,6-trihydroxybenzoic acid; 3,4,5-trihydroxybenzoic acid (gallic acid); and phloroglucinol. However, in vivo formation was likely only for 3,4-dihydroxybenzoic acid; 3,4 dihydroxyphenylacetic acid; 2,4,6-trihydroxybenzoic acid; and 3,4,5 trihydroxybenzoic acid because these were not present in the blank feces, in the animals' normal diet, or in the C genistoides extract. The fact that these amounts were very low suggests further degradation of the metabolites by intestinal microflora or absorption of the cleavage products by the colon. PMID- 20579525 TI - Tea catechin auto-oxidation dimers are accumulated and retained by Caco-2 human intestinal cells. AB - Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (-)-Epigallocatechin (EGC) and (-) epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 mumol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 mumol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% +/- 0.28% and 1.53% +/- 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% +/- 2.1% and 10.1% +/- 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% +/- 2.2% and 4.65% +/- 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% +/- 22% and 29.6% +/- 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium. PMID- 20579528 TI - Iridoid extracts from Ajuga iva increase the antioxidant enzyme activities in red blood cells of rats fed a cholesterol-rich diet. AB - The lyophilized aqueous extract of Ajuga iva (Ai) is able to reduce oxidative stress, which may prevent lipid peroxidation in hypercholesterolemic rats. Iridoids (I) were isolated from Ai. We hypothesized that the antioxidant defense status in red blood cells (RBC) and tissues in rats fed a cholesterol-rich diet and treated with Ai may be correlated to these compounds. Male Wistar rats (n = 32) weighing 120 +/- 5 g were fed a diet containing 1% cholesterol for 15 days. After this phase, hypercholesterolemic (HC) rats were divided into groups, fed the same diet, and received either the same or different doses (5, 10, or 15 mg/kg body weight by intraperitoneal injection) of I for 15 days. Compared with the HC group, total cholesterol value was 1.4- and 1.2-fold lower in the I(5)-HC and I(10)-HC groups. Serum thiobarbituric acid reactive substance content was 2.3 , 2.9-, and 3-fold lower in the I(5)-HC, I(10)-HC, and I(15)-HC groups compared with the HC group. In RBC, glutathione peroxidase, glutathione reductase, and superoxide dismutase activities were significantly higher in the I(5)-HC, I(10) HC, and I(15)-HC groups than the HC group. Liver, heart, and muscle glutathione peroxidase and superoxide dismutase activities were significantly higher in the groups treated with I than the HC group. Muscle glutathione reductase activity was increased 1.4-fold in the I(5)-HC, 1.5-fold in the I(10)-HC, and 1.5-fold in the I(15)-HC group. In HC rats, different doses of I increase the antioxidant enzyme activities in RBC and act differently in tissues. Treatment with I may play an important role in suppressing oxidative stress caused by dietary cholesterol and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia. PMID- 20579529 TI - Calorie restriction at increasing levels leads to augmented concentrations of corticosterone and decreasing concentrations of testosterone in rats. AB - The influence of calorie restriction (CR) on increasing life span, enhancing immunocompetence, and reducing the incidence of age-related diseases is well established. Evidence points to the involvement of neuroendocrine alterations in these beneficial effects. Accordingly, we hypothesized that CR will result in significant alterations to the hormones investigated. Little attention has been directed toward ascertaining the doses of CR required to obtain such alterations and, indeed, whether a dose-response exists. Adult rats were subjected to 1 of 5 dietary regimens: control, CR12.5%, CR25%, CR37.5%, or CR50%. Rats were decapitated 3 weeks following the onset of restriction; and trunk blood was collected and assayed for concentrations of serum adrenocorticotropic hormone, corticosterone, and testosterone, as well as plasma concentrations of noradrenalin and adrenalin. No effect was found as a result of dietary manipulation for serum concentrations of adrenocorticotropic hormone. However, all doses of CR resulted in increased serum corticosterone in a dose-response trend. A dose-response was also observed for serum testosterone, with higher doses of CR associated with lower testosterone. Concentrations of noradrenalin were not found to be altered by any CR dose, although a trend toward a down regulation at CR50% was observed. Plasma adrenalin displayed a biphasic distribution with reductions observed at CR25% and CR50%, although the down regulations only attained statistical significance relative to the CR37.5% and not the control group. As well as reporting the effect of CR on multiple hormones within individual animals, these results go some way in determining the optimal levels of CR needed to induce neuroendocrinologic alterations. PMID- 20579530 TI - The use of circulatory criteria to diagnose death after unsuccessful cardiopulmonary resuscitation. PMID- 20579531 TI - E-learning in resuscitation training - students say they like it, but is there evidence that it works? PMID- 20579532 TI - Kidney transplant function using organs from non-heart-beating donors maintained by mechanical chest compressions. AB - OBJECTIVE: This study aims to determine the failure rate of transplanted kidney grafts in recipients of organs from non-heart beating donors (NHBDs) who have had mechanical chest compressions to maintain a circulation before organ retrieval. METHODS: A retrospective observational study based on review of the emergency medical service database and case histories of NHBDs, and information periodically sent by transplant units about donors and organs. The following variables were studied: age, sex, transfer hospital, time to arrival on the scene of cardiopulmonary arrest, time to arrival in hospital, number and type of organs retrieved, use of mechanical chest compression devices, and kidney function in graft recipients. The study covered the period between January 2008 and November 2009. During 2008 standard manual chest compressions were used and during 2009 mechanical chest compression devices were used. RESULTS: In 39 transplanted kidneys from donors receiving mechanical chest compressions primary failure was documented in recipients on two occasions (5.1%). Kidneys transplanted from donors who had manual chest compressions resulted in three primary failures in recipients (9.1%). The difference between the two groups was not significant (p=0.5). Three patients achieved successful return of spontaneous circulation in the mechanical chest compression group after initiation of the NHBD donor protocol. CONCLUSION: We have described our experience and protocol for non-heart beating donation using victims of out-of-hospital cardiac arrest in whom cardiopulmonary resuscitation has been unsuccessful as donors. Primary kidney graft failure rates in organs from non-heart beating donors is similar when manual or mechanical chest compression devices are used during cardiopulmonary resuscitation. PMID- 20579533 TI - Acquired Gerbode defect after aortic valve replacement. PMID- 20579534 TI - Bicuspid aortic valve disease. AB - Bicuspid aortic valve (BAV) disease is the most common congenital cardiac defect. While the BAV can be found in isolation, it is often associated with other congenital cardiac lesions. The most frequent associated finding is dilation of the proximal ascending aorta secondary to abnormalities of the aortic media. Changes in the aortic media are present independent of whether the valve is functionally normal, stenotic, or incompetent. Although symptoms often manifest in adulthood, there is a wide spectrum of presentations ranging from severe disease detected in utero to asymptomatic disease in old age. Complications can include aortic valve stenosis or incompetence, endocarditis, aortic aneurysm formation, and aortic dissection. Despite the potential complications, 2 large contemporary series have demonstrated that life expectancy in adults with BAV disease is not shortened when compared with the general population. Because BAV is a disease of both the valve and the aorta, surgical decision making is more complicated, and many undergoing aortic valve replacement will also need aortic root surgery. With or without surgery, patients with BAV require continued surveillance. Recent studies have improved our understanding of the genetics, the pathobiology, and the clinical course of the disease, but questions are still unanswered. In the future, medical treatment strategies and timing of interventions will likely be refined. This review summarizes our current understanding of the pathology, genetics, and clinical aspects of BAV disease with a focus on BAV disease in adulthood. PMID- 20579535 TI - Medical professional liability and health care system reform. AB - Few issues elicit more emotion from physicians than medical malpractice. The very word "malpractice" implies guilt and immediately places the involved physician on the defensive. Defensive medicine adds 5% to 9% to the cost of medical care. Numerous solutions have been proposed, but special interests have blocked the implementation of these solutions in most states. Tort reform is necessary to control the escalation of medical costs. PMID- 20579536 TI - The long and winding road to warfarin pharmacogenetic testing. PMID- 20579537 TI - Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. AB - OBJECTIVES: The purpose of this study was to investigate the relationship between angiographic and functional severity of coronary artery stenoses in the FAME (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation) study. BACKGROUND: It can be difficult to determine on the coronary angiogram which lesions cause ischemia. Revascularization of coronary stenoses that induce ischemia improves a patient's functional status and outcome. For stenoses that do not induce ischemia, however, the benefit of revascularization is less clear. METHODS: In the FAME study, routine measurement of the fractional flow reserve (FFR) was compared with angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease. The use of the FFR in addition to angiography significantly reduced the rate of all major adverse cardiac events at 1 year. Of the 1,414 lesions (509 patients) in the FFR guided arm of the FAME study, 1,329 were successfully assessed by the FFR and are included in this analysis. RESULTS: Before FFR measurement, these lesions were categorized into 50% to 70% (47% of all lesions), 71% to 90% (39% of all lesions), and 91% to 99% (15% of all lesions) diameter stenosis by visual assessment. In the category 50% to 70% stenosis, 35% were functionally significant (FFR 0.80). In the category 71% to 90% stenosis, 80% were functionally significant and 20% were not. In the category of subtotal stenoses, 96% were functionally significant. Of all 509 patients with angiographically defined multivessel disease, only 235 (46%) had functional multivessel disease (>or=2 coronary arteries with an FFR or=2.32 event rate 12.2%; p = 0.01). Lower CFR was associated with increased risk for major adverse outcomes (hazard ratio: 1.16, 95% confidence interval: 1.04 to 1.30; p = 0.009). This held true among the 152 women without obstructive coronary artery disease (CAD) (hazard ratio: 1.20, 95% confidence interval: 1.05 to 1.38; p = 0.008). The CFR significantly improved prediction of adverse outcomes over angiographic CAD severity and other risk conditions. CONCLUSIONS: Among women with suspected ischemia and atherosclerosis risk factors, coronary microvascular reactivity to adenosine significantly improves prediction of major adverse outcomes over angiographic CAD severity and CAD risk factors. These findings suggest that coronary microvessels represent novel targets for diagnostic and therapeutic strategies to predict and limit adverse outcomes in women. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554). PMID- 20579541 TI - What can human genetics teach us about the causes of cardiovascular disease? PMID- 20579542 TI - Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy. AB - OBJECTIVES: We sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions. BACKGROUND: Epidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk. METHODS: A systematic MEDLINE search identified lipid intervention RCTs with >or=1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm. RESULTS: A total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001). CONCLUSIONS: There is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking. PMID- 20579543 TI - Low high-density lipoprotein cholesterol and chronic disease risk marker or causal? PMID- 20579544 TI - Cardiac origins of the postural orthostatic tachycardia syndrome. AB - OBJECTIVES: The purpose of this study was to test the hypothesis that a small heart coupled with reduced blood volume contributes to the postural orthostatic tachycardia syndrome (POTS) and that exercise training improves this syndrome. BACKGROUND: Patients with POTS have marked increases in heart rate during orthostasis. However, the underlying mechanisms are unknown and the effective therapy is uncertain. METHODS: Twenty-seven POTS patients underwent autonomic function tests, cardiac magnetic resonance imaging, and blood volume measurements. Twenty-five of them participated in a 3-month specially designed exercise training program with 19 completing the program; these patients were re evaluated after training. Results were compared with those of 16 healthy controls. RESULTS: Upright heart rate and total peripheral resistance were greater, whereas stroke volume and cardiac output were smaller in patients than in controls. Baroreflex function was similar between groups. Left ventricular mass (median [25th, 75th percentiles], 1.26 g/kg [1.12, 1.37 g/kg] vs. 1.45 g/kg [1.34, 1.57 g/kg]; p < 0.01) and blood volume (60 ml/kg [54, 64 ml/kg] vs. 71 ml/kg [65, 78 ml/kg]; p < 0.01) were smaller in patients than in controls. Exercise training increased left ventricular mass and blood volume by approximately 12% and approximately 7% and decreased upright heart rate by 9 beats/min [1, 17 beats/min]. Ten of 19 patients no longer met POTS criteria after training, whereas patient quality of life assessed by the 36-item Short-Form Health Survey was improved in all patients after training. CONCLUSIONS: Autonomic function was intact in POTS patients. The marked tachycardia during orthostasis was attributable to a small heart coupled with reduced blood volume. Exercise training improved or even cured this syndrome in most patients. It seems reasonable to offer POTS a new name based on its underlying pathophysiology, the "Grinch syndrome," because in this famous children's book by Dr. Seuss, the main character had a heart that was "two sizes too small." PMID- 20579546 TI - Inflammatory abdominal aortic aneurysm successfully treated with steroid therapy. PMID- 20579545 TI - Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion. AB - OBJECTIVES: We examined the effects of the flavanol (-)-epicatechin on short- and long-term infarct size and left ventricular (LV) structure and function after permanent coronary occlusion (PCO) and the potential involvement of the protective protein kinase B (AKT)/extracellular signal-related kinase (ERK) signaling pathways. BACKGROUND: (-)-epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. METHODS: (-)-epicatechin (1 mg/kg daily) treatment was administered via oral gavage to 250 g male rats for 10 days before PCO and was continued afterward. The PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. The LV morphometric features and function were measured 48 h and 3 weeks after PCO. RESULTS: In the 48-h group, treatment reduced infarct size by 52%. There were no differences in hemodynamics among the different groups (heart rate and aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart and body weight, and LV chamber diameter versus sham. The PCO plus (-) epicatechin group values were comparable with those of the sham plus (-) epicatechin group. Treatment resulted in a 33% decrease in myocardial infarction size. The LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas the (-)-epicatechin curves were comparable with those of the sham group. The LV scar area strains were significantly improved with (-) epicatechin. CONCLUSIONS: These results demonstrate the unique capacity of (-) epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure and function. The cardioprotective mechanism(s) of (-)-epicatechin seem to be unrelated to AKT or ERK activation. (-)-epicatechin warrants further investigation as a cardioprotectant. PMID- 20579547 TI - Aspirin for primary prevention of cardiovascular events in people with diabetes. PMID- 20579548 TI - Survival in out-of-hospital cardiac arrest before and after use of advanced postresuscitation care: a survey focusing on incidence, patient characteristics, survival, and estimated cerebral function after postresuscitation care. AB - BACKGROUND: Knowledge of the epidemiology of postresuscitation care is insufficient. We describe the epidemiology of postresuscitation care in a community from a 26-year perspective, focusing on incidence, patient characteristics, survival, and estimated cerebral function in relation to intensified postresuscitation care and initial arrhythmia. METHODS: The study included patients with out-of-hospital cardiac arrest (OHCA) who were brought alive to a hospital ward in Goteborg, Sweden, between 1980 and 2006. Two periods (1980-2002 and 2003-2006) were compared. RESULTS: In all, 1603 patients were included. For age, sex, and history, no significant differences between the 2 periods were seen. There was a significant multiple increase in bystander cardiopulmonary resuscitation, the use of coronary angiography, coronary revascularization, and therapeutic hypothermia. The number of patients found in ventricular fibrillation (VF) decreased (P = .011). For all patients, 1-year survival did not change significantly (27% vs 32%; P = .14). Among patients found in VF, an increase in 1-year survival was found (37% vs 57%; P < .0001), whereas no significant change was seen in nonshockable rhythm (10% vs 7%; P = .38). Survivors to discharge displaying low cerebral function (ie, cerebral performance categories score >or=3) decreased from 28% to 6% (P = .0006) among all patients. CONCLUSION: After the introduction of a more intensified postresuscitation care, there was no overall improvement in survival but signs of an improved cerebral function among survivors. There was a marked increase in survival among patients found in a shockable rhythm but not among those found in a nonshockable rhythm. PMID- 20579549 TI - Prehospital intervention probability score: a novel method for determining necessity of emergency medical service units. AB - OBJECTIVE: This article models use of emergency medical services (EMS) within a defined geographical area. Our goal was to develop an original quantitative method to delineate the need for EMS units within a geographical population. METHODS: Use of the EMS system within 11 municipalities was analyzed in 2007. The geospatial distributions of interventions during this year were examined, as well as the population dynamics of the region. A statistical model to determine the probability of an individual within the call area requiring an intervention was proposed using weighted population statistics and the application of an intervention probability. RESULTS: The observed interventional probability increased exponentially with age, notably after the age of 75. Areas with higher proportions of elderly residents had substantially higher rates of intervention and EMS use. Municipality H had the largest age-group of 20 to 24 years with an intervention probability of 0.34% (95% confidence interval [CI], 0.24-0.44), their more than 85-year age-group also had the largest intervention probability of 19.54% (95% CI, 15.60-23.48). CONCLUSIONS: Contrary to current practice patterns of placing paramedic units in regions of greatest population density, we established a formula based on population vs intervention probability. We found the actual numbers of interventions performed are not dependent solely on population size but also are affected by the age of the population being served. This is particularly relevant to growing elderly communities. This determination will aid in the disbursement of limited prehospital resources in regions by improving availability of EMS personnel. PMID- 20579550 TI - Ultrasound guidance for central venous catheter placement: results from the Central Line Emergency Access Registry Database. AB - BACKGROUND: Ultrasound guidance of central venous catheter (CVC) insertion improves success rates and reduces complications and is recommended by several professional and regulatory organizations. METHODS: This is a prospective observational study using data extracted from the Central Line Emergency Access Registry database, a multicenter online registry of CVC insertions from medical centers throughout the United States. We compared success rates with ultrasound and with the anatomic-landmark technique. RESULTS: A total of 1250 CVC placement attempts by emergency medicine residents during the study period were selected from the Central Line Emergency Access Registry database. Because a few attempts (n = 28) were made to place lines in either the left or right supraclavicular locations, data on these attempts were eliminated from the analysis. A total of 1222 CVC attempts from 5 institutions were analyzed. Successful placement on the first attempt occurred in 1161 (86%) cases and varied according to anatomic location. Ultrasound guidance was used in 478 (41%) of the initial attempts. The remainder of placements were presumably placed using the anatomic-landmark technique based on visible surface and palpatory subcutaneous structures. Overall successful placement rate did not vary according to the use of ultrasound guidance, nor did it vary at different anatomic sites. However, ultrasound was found to be significant for reducing the total number of punctures per attempt (P < .02, t = 2.30). CONCLUSIONS: Our study did not observe improved success with the use of ultrasound for CVC cannulation on the first attempt, but we did observe a reduced number of total punctures per attempt. PMID- 20579551 TI - Effects of high-urgency ambulance transportation on pro-B-type natriuretic peptide levels in patients with heart failure. AB - OBJECTIVES: We hypothesized that pro-B-type natriuretic peptide (proBNP) levels in venous blood increase in patients with acute out-of-hospital heart failure because of stress during emergency ambulance transportation, and furthermore, we wanted to show if there is an effect of increasing proBNP levels on hemodynamic parameters. METHODS: Venous proBNP levels, visual analog scale (VAS) for pain and anxiety before and after transportation, heart rate, blood pressure, and transcutaneous Spo(2) were measured every 3 minutes in 32 patients with defined clinical signs of heart failure. RESULTS: ProBNP levels increased significantly (P < .01) during transportation (278.13 +/- 113.20 vs 984.67 +/- 627.33 pg/mL), whereas heart rate and mean blood pressure remained almost stable. There was no significant change in VAS for pain and anxiety (3.79 +/- 3.70 and 2.89 +/- 3.01 vs 2.13 +/- 3.30 and 1.57 +/- 2.78). CONCLUSION: A rapid increase in proBNP levels was shown in patients with acute out-of-hospital heart failure during emergency ambulance transportation but no significant changes in hemodynamic parameters. PMID- 20579553 TI - Physiologic effects of prolonged conducted electrical weapon discharge in ethanol intoxicated adults. AB - OBJECTIVES: This study examines the physiologic effects of prolonged conducted electrical weapon (CEW) exposure on alcohol-intoxicated adult subjects. METHODS: Adult volunteers were recruited at a TASER International training conference. All subjects ingested mixed drinks until clinical intoxication or until a minimum breath alcohol level of 0.08 mg/dL was achieved. Blood samples for venous pH, Pco(2), bicarbonate, and lactate were measured in all subjects at baseline, immediately after alcohol ingestion, immediately after exposure to a 15-second TASER X26 discharge (Taser International Inc, Scottsdale, AZ), and 24 hours post alcohol ingestion. Laboratory values were compared at sampling times using repeated-measure analysis of variance. A focused analysis comparing time points within groups was then performed using paired t tests. RESULTS: Twenty-two subjects were enrolled into the study. There was a decrease in pH and bicarbonate and an increase in lactate after alcohol ingestion. There was a further increase in lactate and drop in pH after CEW exposure. No subject experienced a significant adverse event. All values had returned to baseline levels at 24 hours except lactate, which demonstrated a small but clinically insignificant increase. CONCLUSIONS: Prolonged continuous CEW exposure in the setting of acute alcohol intoxication has no clinically significant effect on subjects in terms of markers of metabolic acidosis. The acidosis seen is consistent with what occurs with ethanol intoxication or moderate exertion. PMID- 20579552 TI - Reliability of anion gap calculated from data obtained using a blood gas analyzer: is the probability of error predictable? AB - BACKGROUND: Anion gap (AG) is a useful index for assessing the clinical condition of critically ill patients especially in intoxication. Recently, AG can be obtained easily using a blood gas analyzer (BGA); however, its reliability requires validation. METHODS: We enrolled patients who simultaneously underwent blood gas analysis and blood test in the central hospital laboratory and patients who visited the emergency department of our hospital from January 1, 2004, to December 31, 2007. The deviation of AG calculated using the BGA and that calculated by the central hospital laboratory were extracted. From the data obtained using the BGA, the independent risk factor causing a significant error in AG was statistically analyzed. RESULTS: A total of 2922 patients were enrolled, of which 339 were defined as the significant error group. Male sex, abnormal Hco(3)(-), abnormal lactate, abnormal K, abnormal Cl, and abnormal Na were the independent risk factors producing the significant error. The results indicate that regardless of whether the original electrolyte data of the patients are abnormal, when the electrolyte measurement results obtained using the BGA are abnormal, the calculated AG might show a significant error. In addition, the fact that lactate was determined as a risk factor indicates that AG might be more useful in patients who have intoxication than in those under an unstable state in terms of vital signs. CONCLUSION: When risk factors are present, the medical condition of a patient should be reevaluated by comparing results without heavily relying on the AG obtained by a BGA. PMID- 20579554 TI - Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration. AB - BACKGROUND: Compared to fixed-dose single-vial drug administration in adults, pediatric drug dosing and administration requires a series of calculations, all of which are potentially error prone. The purpose of this study is to compare error rates and task completion times for common pediatric medication scenarios using computer program assistance vs conventional methods. METHODS: Two versions of a 4-part paper-based test were developed. Each part consisted of a set of medication administration and/or dosing tasks. Emergency department and pediatric intensive care unit nurse volunteers completed these tasks using both methods (sequence assigned to start with a conventional or a computer-assisted approach). Completion times, errors, and the reason for the error were recorded. RESULTS: Thirty-eight nurses completed the study. Summing the completion of all 4 parts, the mean conventional total time was 1243 seconds vs the mean computer program total time of 879 seconds (P < .001). The conventional manual method had a mean of 1.8 errors vs the computer program with a mean of 0.7 errors (P < .001). Of the 97 total errors, 36 were due to misreading the drug concentration on the label, 34 were due to calculation errors, and 8 were due to misplaced decimals. Of the 36 label interpretation errors, 18 (50%) occurred with digoxin or insulin. CONCLUSIONS: Computerized assistance reduced errors and the time required for drug administration calculations. A pattern of errors emerged, noting that reading/interpreting certain drug labels were more error prone. Optimizing the layout of drug labels could reduce the error rate for error-prone labels. PMID- 20579555 TI - Improving Crotalidae polyvalent immune Fab reconstitution times. AB - BACKGROUND: Crotalidae polyvalent immune Fab (CroFab) is used to treat rattlesnake envenomations in the United States. Time to infusion may be a critical factor in the treatment of these bites. Per manufacturer's instructions, 10 mL of sterile water for injection (SWI) and hand swirling are recommended for reconstitution. We wondered whether completely filling vials with 25 mL of SWI would result in shorter reconstitution times than using 10-mL volumes and how hand mixing compared to mechanical agitation of vials or leaving vials undisturbed. METHODS: Six sets of 5 vials were filled with either 10 mL or 25 mL. Three mixing techniques were used as follows: undisturbed; agitation with a mechanical agitator; and continuous hand rolling and inverting of vials. Dissolution was determined by observation and time to complete dissolution for each vial. Nonparametric 2-tailed P values were calculated. RESULTS: Filling vials completely with 25 mL resulted in quicker dissolution than using 10-mL volumes, regardless of mixing method (2-tailed P = .024). Mixing by hand was shorter than other methods (P < .001). Reconstitution with 25 mL and hand mixing resulted in the shortest dissolution times (median, 1.1 minutes; range, 0.9-1.3 minutes). This appeared clinically important because dissolution times using 10 mL and mechanical rocking of vials (median, 26.4 minutes) or leaving vials undisturbed (median, 33.6 minutes) was several-fold longer. CONCLUSION: Hand mixing after filling vials completely with 25 mL results in shorter dissolution times than using 10 mL or other methods of mixing and is recommended, especially when preparing initial doses of CroFab. PMID- 20579557 TI - Accurate prediction of the needle depth required for successful lumbar puncture. AB - INTRODUCTION: The aim of this study is to formulate an accurate estimate of the spinal needle depth for a successful lumbar puncture in pediatric patients. METHODS: This is a prospective study of pediatric oncology patients who had lumbar punctures in the course of their treatment. The distance from skin entry point to the tip of the spinal needle was measured after lumbar punctures were performed. The relationship between the depth of needle insertion with weight, height, body surface area, body mass index, intervertebral space used, ethnicity, and sex of patient were studied. Predictive statistical models were used for the formulation of the ideal lumbar puncture needle depth. RESULTS: Two hundred seventy-nine patients who had nontraumatic lumbar punctures were studied. The patient characteristics were as follows: age, 0.5 to 15 years; weight, 7 to 63 kg; and height, 70 to 162 cm. Analysis using multiple regression tests with stepwise approach showed a strong relationship between the lumbar puncture needle depth and weight/height ratio. By using a predictive regression model, ideal depth of needle insertion (cm) = 10 [weight(kg)/height(cm)] + 1, with a regression coefficient r = 0.77. CONCLUSION: This formula is accurate and practical with less complex calculations. However, further validation in a prospective study will be needed. PMID- 20579556 TI - Topical antacid therapy for capsaicin-induced dermal pain: a poison center telephone-directed study. AB - PURPOSE: The study aimed to assess the effects of topical antacids for treatment of capsaicin-induced dermal pain after exposure to capsaicin containing hot peppers, personal protection sprays, or topical creams. PROCEDURES: Participants of the study were California Poison Control System (CPCS) hotline callers 12 years or older with dermal pain from exposure to capsaicin-containing products or plants. Participants were instructed to apply a topical antacid and assessed for perceived pain (using a 0-10 scale) pre- and posttreatment. A positive response was defined as a sustained reduction of pain 33% or more within 30 minutes or achieving a pain score of 0 to 1. MAIN FINDINGS: Of 93 eligible patients, 64 applied antacids and had outcome data available. Patients contacted the CPCS a median of 1 hour postexposure with a median initial pain score of 7.5/10. Thirty six (56%) were exposed to unrefined (natural) peppers and 28 (44%) to refined capsaicin (eg, capsaicin-containing cream). Before calling the CPCS, 57 (89%) attempted at least one treatment. Forty-five (70%) reported positive response to antacid treatment as a 33% reduction in pain in 30 minutes (n = 17), a reduction in pain to a score of 0 to 1 (n = 3), or both (n = 25). A 33% reduction in pain within 30 minutes was associated with exposure to refined capsaicin (odds ratio, 3.37; 95% confidence interval, 0.98-11.66). Concomitant refined capsaicin exposure and early treatment (<1 hour of symptoms) was associated with even greater odds of response (odds ratio, 5.4; 95% confidence interval, 1.4-21.2). CONCLUSION: Topical application of antacids for capsaicin-induced pain is effective, particularly in early treatment of exposure to refined capsaicin. PMID- 20579558 TI - Which stroke symptoms prompt a 911 call? A population-based study. AB - INTRODUCTION: Many studies show that a major barrier to short-term treatment of stroke is patient or bystander delay in responding to stroke symptoms. Most studies have found that less than half of stroke/transient ischemic attack (TIA) events result in a 911 call. We sought to determine which symptoms prompt the public to call 911. METHODS: A population of 1.3 million within a 5-county region was screened for TIA and all strokes in 1999 using all local hospital International Classification of Diseases, Ninth Edition, codes for stroke (430 436) during 1999. Documented stroke symptoms were abstracted from the medical record. Symptoms were grouped as weakness, numbness, speech/language, confusion/decreased level of consciousness, headache, visual changes, and dizziness/vertigo/coordination. Cases included in this analysis had their strokes at home or work and presented to an emergency department. Logistic regression assessed which symptoms predicted a 911 call, adjusting for age, race, sex, prior stroke, baseline disability, overall stroke severity, home vs work, and stroke subtype. RESULTS: Two thousand nine hundred seventy-five stroke/TIA patients met inclusion criteria, of whom 40% used emergency medical services. After adjustment, symptoms that increased odds of a 911 call were weakness, confusion/decreased level of consciousness, speech/language, and dizziness/coordination/vertigo. Numbness was less likely to result in a 911 call as were visual changes. The presence of headache was not associated with the decision to call 911. DISCUSSION: The public appears to respond differently based on the type of stroke symptom, independent of overall severity. Public awareness messages regarding stroke warning signs should be designed with this in mind. PMID- 20579559 TI - Can urine dipstick predict an elevated serum creatinine? AB - OBJECTIVE: Chart review studies have suggested that point-of-care urine dipstick testing may accurately predict an elevation in serum creatinine (Cr). We aimed to prospectively evaluate the test characteristics of proteinuria/hematuria in predicting elevated serum Cr. METHODS: A prospective, observational study was conducted between March 2007 and June 2008 at 2 affiliated, urban hospitals with an annual emergency department census of 150,000. Patients undergoing laboratory urinalysis, point-of-care urine dipstick, and a serum chemistry panel were enrolled. Trained research assistants collected data on consecutive patients 18 hours per day using preformatted data forms and entry into an anonymized Access (Microsoft, Seattle, Wash) database. Demographic baseline variables including age, sex, chief complaint, vital signs, and source of sample (catheter vs "clean catch") were also collected. An elevated Cr level was defined as greater than 1.3 based on the laboratory reference range. Standard statistical methods were used to calculate diagnostic test operating characteristics of proteinuria or hematuria as a predictor of elevated serum Cr. RESULTS: Five thousand four hundred sixteen subjects were enrolled with 28.3% male and a mean age of 50.2 years. Elevated serum Cr greater than 1.3 mg/dL was found in 13.9% (755/5416) of subjects. The sensitivity of either proteinuria or hematuria for elevated Cr was 82.5% (95% confidence interval [CI], 80%-85%) and specificity was 34.4% (95% CI, 33%-36%). Positive predictive value was 16.9% (95% CI, 16%-18%) and negative predictive value was 92.4% (95% CI, 91-94%). The likelihood ratio for a positive test was 1.3 (95% CI, 1.1-1.5), and the likelihood ratio for a negative test was 0.5 (95% CI, 0.3-0.8). CONCLUSIONS: Although negative predictive value was high, the presence of proteinuria/hematuria was only moderately predictive of elevated serum Cr level. PMID- 20579560 TI - Can retinal changes predict coronary artery disease in elderly hypertensive patients presenting with angina? AB - BACKGROUND: The prevalence of coronary artery disease (CAD) has been increasing in India, and so is the population of elderly patients with hypertension. In the predominantly resource-poor setting prevailing in India, this study is an effort to analyze the accuracy of retinal changes in predicting CAD among a cohort of elderly patients with hypertension presenting to the emergency department with angina. METHODS: A total of 72 elderly patients with hypertension older than 65 years presenting to the emergency department with acute angina were studied. Optic fundi were assessed for retinopathy after pupillary dilatation, which were photographed. All patients underwent coronary angiogram, and the presence or absence of CAD was determined. RESULTS: Mean +/- SD age of the participants was 72.95 +/- 6.51 years, and there were 39 men (54.2%) and 33 women (45.8%). Prevalence of CAD and retinopathy was 40.8% and 30.6%, respectively. Coronary artery disease showed a strong association with retinopathy (P < .0001). Male sex (P = .035), microalbuminuria (P = .025), and increased high-sensitivity C reactive protein (P = .001) were identified as risk factors for CAD. Tests of accuracy for retinopathy as a predictor of CAD showed a likelihood ratio of a positive test and likelihood ratio of a negative test of 3.92 and 0.52, respectively. Area under the receiver operating characteristics curve was 70.6%. CONCLUSION: Prevalence of CAD (40.8%) and retinopathy (30.6%) was quite high in our cohort of elderly patients with hypertension. Retinal changes of any grade have a moderate accuracy in predicting CAD and, hence, may be used as an early screening tool in a resource poor setting. PMID- 20579561 TI - Staffing of the ED by non-emergency medicine-trained personnel: the VA experience. AB - STUDY OBJECTIVE: VA (Veteran's Affairs) emergency departments (EDs) are generally staffed with physicians trained in internal medicine (IM), although recently, a movement has begun toward hiring emergency medicine (EM)-trained staff. At our institution, the ED is staffed by physicians of both specialties. This study examines the frequency of unscheduled return visits to the ED in an effort to compare the quality of emergency care given by physicians trained in IM and EM. METHODS: The record of all visits to a VA hospital ED during a 90-day period were examined, and all those visits resulting in a return ED visit within the 30 subsequent days were noted. RESULTS: The charts of 2891 consecutive ED patients were examined. The rate of revisits was significantly higher for the IM than for the EM-trained physicians (8.9% vs 5.5%, respectively; P < .001). The IM-trained physicians had a significantly higher rate of admissions upon revisit within 30 days than did the EM-trained physicians (3.5% vs 1.9%, respectively; P = .014). The IM-trained staff had lower initial hospitalization rates than the EM physicians (20% vs 43%, respectively; P < .0001). CONCLUSIONS: The IM-trained physicians were less likely to hospitalize patients, although this can be partially explained by the lower acuity of patients during the hours that they covered. The IM-trained physicians were significantly more likely to have a patient return after discharge and also more likely to have a patient return in need of hospitalization. This may reflect a difference in training for the rapid diagnosis and risk stratification of ED patients. PMID- 20579562 TI - An initial description of a sonographic sign that verifies intrathoracic chest tube placement. AB - PURPOSE: An initial description of a sonographic finding predictive of intrathoracic chest tube placement. METHODS: This was a prospective observational study using unembalmed cadaveric models. Chest tubes were randomly placed intra- and extrathoracically and evaluated using ultrasound. Chest tube location was confirmed using blunt dissection followed by tactile and visual confirmation. Sonographers were blinded to chest tube position. Sonographic images obtained in a transverse orientation revealed a subcutaneous hyperechoic arc, created by the chest tube, at the insertion site. The path of the hyperechoic arc was followed cephalad. Disappearance of the hyperechoic arc signified intrathoracic chest tube placement. In contrast, continuation of a subcutaneous hyperechoic arc for the full length of the chest tube signified extrathoracic chest tube placement (the Disappearance/Intrathoracic, Continuation/Extrathoracic sign). RESULTS: Ultrasound was used to evaluate 48 chest tube placements. All chest tube locations were identified correctly. In differentiating intra- vs extrathoracic chest tube placement, the Disappearance/Intrathoracic, Continuation/Extrathoracic sign revealed a sensitivity of 100% (95% confidence interval, 83%-100%) and a specificity of 100% (95% confidence interval, 83%-100%). CONCLUSIONS: In this small study, bedside ultrasound appears to be highly sensitive and specific in differentiating intra- versus extrathoracic chest tube placement. PMID- 20579563 TI - Predictors of acute decompensation after admission in ED patients with sepsis. AB - PURPOSES: The aim of the study was to identify predictors of acute decompensation within 48 hours of admission among infected emergency department (ED) patients admitted to a regular nursing floor. PROCEDURES: This used a case control study of infected ED patients admitted to a regular nursing floor and who received a discharge diagnosis of sepsis. A multivariate logistic regression model was constructed with the dependent variable as transfer to an intensive care unit (ICU) within 48 hours of admission. FINDINGS: Seventy-eight patients were enrolled-34 in the ICU group and 44 in the floor group. Only low bicarbonate (<20 mmol/L) (odds ratio [OR], 7.40; 95% confidence interval [CI], 2.35-23.30) and absence of fever (OR, 3.66; 95% CI, 1.11-12.60) were predictive of ICU transfer. CONCLUSIONS: Among infected ED patients admitted to a regular floor, absence of fever and low bicarbonate were independently associated with ICU transfer within 48 hours. Particular attention should be paid to similar patients to ensure appropriate identification of severe infection and appropriate risk stratification. PMID- 20579564 TI - Baseline drug history is also important for interpretation of the electrocardiogram. PMID- 20579565 TI - The differential diagnosis includes reversible cerebral vasoconstrictor syndrome. PMID- 20579566 TI - More rigorous risk profiling of prospective candidates for plasminogen activator therapy. PMID- 20579567 TI - Lightning injury may cause abrupt cerebral salt wasting syndrome. PMID- 20579568 TI - Kounis syndrome captured by coronary angiography computed tomography. PMID- 20579569 TI - Ciprofloxacin-induced immunoglobulin A disease. PMID- 20579570 TI - Spontaneous coronary artery dissection in a postpartum woman presenting with chest pain. PMID- 20579571 TI - Spontaneous intramural duodenal hematoma--a rare cause of upper gastrointestinal obstruction. PMID- 20579572 TI - Lethal acute poisoning with potassium ferrocyanide. PMID- 20579573 TI - Fulminant endogenous gas gangrene: role of ultrasonography in the emergency setting. PMID- 20579575 TI - Distal coronary macroemboli and thrombus aspiration in a patient with acute myocardial infarction. PMID- 20579574 TI - Lemierre syndrome associated with group A streptococcal infection. PMID- 20579576 TI - Intraocular mass causing acute angle-closure glaucoma. PMID- 20579577 TI - The early presence of pneumatosis in traumatic colonic perforation: a sequential computed tomography demonstration. PMID- 20579578 TI - Intestinal ascariasis presenting with chronic gastrointestinal complaints. PMID- 20579579 TI - A case of cerebral amyloid angiopathy mimicking diffuse axonal injury. PMID- 20579581 TI - He who pays the piper... PMID- 20579580 TI - Painless type B aortic dissection presenting as acute congestive heart failure. PMID- 20579582 TI - Clinical outcomes and medical care costs among medicare beneficiaries receiving therapy for peripheral arterial disease. AB - BACKGROUND: Peripheral arterial disease (PAD) is a common disorder with multiple options for treatment, ranging from medical interventions, surgical revascularization, and endovascular therapy. Despite the explosive advances in endovascular therapy, cost-effective methods of care have not been well defined. We analyze therapeutic strategies, outcomes, and medical cost of treatment among Medicare patients with PAD. METHODS AND RESULTS: Patients who underwent therapy for PAD were identified from a 5% random sample of Medicare beneficiaries from Medicare Standard Analytic Files for the period 1999-2005. Clinical outcomes (death, amputation, new clinical symptoms related to PAD) and direct medical costs were examined by chosen revascularization options (endovascular, surgical, and combinations). One-year PAD prevalence increased steadily from 8.2% in 1999 to 9.5% in 2005. The risk-adjusted time to first post-treatment clinical outcome was lowest in those treated with "percutaneous transluminal angioplasty (PTA) or atherectomy and stents" (HR, 0.829; 95% CI, 0.793-0.865; p < 0.001) and stents only (HR, 0.904; 95% CI, 0.848-0.963; p = 0.002) compared with PTA alone. The lowest per patient risk-adjusted costs during the quarter of the first observed treatment were associated with "PTA and stents" ($15,197), and stents only ($15,867). Risk-adjusted costs for surgical procedures (bypass and endarterectomy) were $27,021 during the same period. Diabetes was present in 61.7% of the PAD population and was associated with higher risks of clinical events and higher medical costs compared with PAD patients without diabetes. CONCLUSION: The clinical and economic burden of PAD in the Medicare population is substantial, and the interventions used to treat PAD are associated with differences in clinical and economic outcomes. Prospective cost-effectiveness analyses should be included in future PAD therapy trials to inform payers and providers of the relative value of available treatment options. PMID- 20579583 TI - Culprit coronary lesions requiring percutaneous coronary intervention after vascular surgery often arise from in-stent restenosis of bare metal stents. AB - BACKGROUND: The natural history of coronary artery disease (CAD) after vascular surgery is poorly defined. The aim of this study was to determine the temporal change of coronary artery lesions requiring revascularization with a percutaneous coronary intervention (PCI) after elective vascular surgery and to determine the utility of preoperative biomarkers on predicting those patients at risk for new coronary lesions. METHODS: The Coronary Artery Revascularization Prophylaxis Trial tested the long-term survival benefit of coronary artery revascularization before elective vascular surgery. Among randomized patients who subsequently required PCI after surgery, the stenosis of the culprit lesion from the follow-up angiogram was compared with the preoperative vessel stenosis at the identical site on the baseline angiogram. RESULTS: A total of 30 patients underwent PCI for progressive symptoms at a median of 11.5 (interquartiles: 4.5-18.5) months postsurgery. Of 30 patients, 16 (53%) had nonobstructive CAD preoperatively (group 1) with a stenosis that increased from 17 +/- 6% to 91 +/- 2% (P < 0.01) and 14 (47%) had severe CAD at the culprit site preoperatively (group 2), with a stenosis that increased 89 +/- 2% (P = 0.15). The only biomarker that was an identifier of early coronary artery lesion formation in group 1 compared with group 2 patients was a higher baseline homocysteine level (14.6 +/- 1.4 vs. 10.6 +/- 0.7 mg/dL; P = 0.02). CONCLUSIONS: Culprit coronary artery lesions requiring PCI after an elective vascular operation often arise from in-stent restenosis. Therapies that either stabilize existing plaques or prevent restenosis, particularly among patients with elevated homocysteine levels, have the greatest promise for improving postoperative outcomes. PMID- 20579584 TI - Arterial access for thoracic endograft placement. AB - BACKGROUND: Endovascular repair of thoracic aortic disease continues to evolve since FDA approval of the first thoracic endograft in the United States in March 2005. Certain anatomic characteristics, including adequacy of arterial access, remain a significant limiting factor in thoracic endovascular repair. In clinical trials evaluating thoracic endografts, vascular access complications occurred in >20% of cases. The purpose of this study is to evaluate the arterial access and the selective use of the ascending aorta for thoracic endograft placement. METHOD: A retrospective review was performed for patients who underwent thoracic endograft placement between May 2005 and April 2009 (4 years since FDA approval of the first thoracic endograft). Patient records were reviewed for the indication for the procedure, type of arterial access, technical success, and access-related complications. RESULTS: Seventy-nine thoracic endografts were placed during the study period. The indications for endograft placement included 53 aneurysms, 10 traumatic lesions, 6 endoleaks, 4 dissections, 3 penetrating ulcers, 2 bleeding aortic fistulas, and 1 thoracic diverticulum. Retrograde access was used in 70 cases (89%): 60 femoral (76%) and 10 aortoiliac (13%). Antegrade access through a 10-mm polyester graft anastomosed to the ascending aorta was used in nine cases (11%). These procedures included endograft placement with proximal elephant trunk creation in six cases, endograft-alone in two cases, and combination with proximal arch reconstruction/debranching in one case. There was 100% technical success for all cases. The overall access-related complication rate was 6%. There were no complications with antegrade access through the ascending aorta or with aortoiliac access. There were five complications in the femoral access group (three iliac artery dissection, one iliac artery injury, and one femoral artery injury). CONCLUSIONS: Access selection is an important part of the preoperative planning of endovascular procedures. Choosing the most appropriate access for a patient will decrease the access-associated complication rate. In addition, selected patients with poor aortoiliac access and those that require debranching or elephant trunk procedures may benefit from antegrade access. PMID- 20579585 TI - Efficacy of bosentan in digital ischemic ulcers. AB - Thromboangiitis obliterans (also known as Buerger's disease) is an inflammatory vascular disorder that affects small and medium-sized arteries and veins in the extremities. There is no specific treatment and the only effective intervention is absolute cessation of tobacco use. Endothelial dysfunction appears to be of relevance to this condition and a report has even found that high serum levels of endothelin correlate with the presence of necrosis. We report two cases of digital necrosis showing a very satisfactory response to treatment with bosentan, a dual endothelin receptor antagonist. PMID- 20579586 TI - Open and endovascular treatment for pseudoaneurysms of the superior mesenteric artery. AB - BACKGROUND: Pseudoaneurysms of the superior mesenteric artery are rare, and their natural history is characterized by their tendency to rupture, thereby leading to a high mortality rate. Compared with classic surgical techniques (open), in recent years the possibility of endovascular treatment has increased. RESULTS: We report the cases of two patients with a pseudoaneurysm of the superior mesenteric artery. Each case was successfully treated in a different way: open and endovascular surgery. CONCLUSION: Despite the advantages (less risk for the patient) and good results obtained with endovascular surgery, this cannot completely replace open surgery. The choice of the most appropriate therapeutic option for pseudoaneurysms of the superior mesenteric artery depends on the state of the patient and the characteristics of the lesion. Open and endovascular surgical techniques are complementary, not mutually exclusive, techniques. PMID- 20579587 TI - Novel treatment for chylothorax after esophagectomy with 50% glucose pleurodesis. AB - Chylothorax is characterized by the presence of chyle in the pleural space and cardiothoracic surgery accounts for nearly half of all the cases. Treatment of chylothorax has traditionally been nonoperative, with alternative medical therapies involving the administration of octreotide or pleurodesis. Pleurodesis with chemical agents has previously been reported, but never with 50% glucose and 0.1% xylocaine. Herein, we report a successful method of intrapleural instillation of 50% glucose and 0.1% xylocaine to treat chylothorax. Five patients treated with this method were all recovered rapidly. This method can generate extensive adherence and prevent the effusion of the chylous fluid with minor side effects. PMID- 20579588 TI - "Re: Management of median arcuate ligament syndrome: a new paradigm". PMID- 20579590 TI - Borage oil in the treatment of atopic dermatitis. AB - Nutritional supplementation with omega-6 essential fatty acids (omega-6 EFAs) is of potential interest in the treatment of atopic dermatitis. EFAs play a vital role in skin structure and physiology. EFA deficiency replicates the symptoms of atopic dermatitis, and patients with atopic dermatitis have been reported to have imbalances in EFA levels. Although direct proof is lacking, it has been hypothesized that patients with atopic dermatitis have impaired activity of the delta-6 desaturase enzyme, affecting metabolism of linoleic acid to gamma linolenic acid (GLA). However, to date, studies of EFA supplementation in atopic dermatitis, most commonly using evening primrose oil, have produced conflicting results. Borage oil is of interest because it contains two to three times more GLA than evening primrose oil. This review identified 12 clinical trials of oral or topical borage oil for treatment of atopic dermatitis and one preventive trial. All studies were controlled and most were randomized and double-blind, but many were small and had other methodological limitations. The results of studies of borage oil for the treatment of atopic dermatitis were highly variable, with the effect reported to be significant in five studies, insignificant in five studies, and mixed in two studies. Borage oil given to at-risk neonates did not prevent development of atopic dermatitis. However, the majority of studies showed at least a small degree of efficacy or were not able to exclude the possibility that the oil produces a small benefit. Overall, the data suggest that nutritional supplementation with borage oil is unlikely to have a major clinical effect but may be useful in some individual patients with less severe atopic dermatitis who are seeking an alternative treatment. Which patients are likely to respond cannot yet be identified. Borage oil is well tolerated in the short term but no long term tolerability data are available. PMID- 20579591 TI - Polyunsaturated fatty acids and atopic dermatitis. PMID- 20579592 TI - Late introduction and poor diversity were the main weaknesses of complementary foods in a cohort study in rural Burkina Faso. AB - OBJECTIVE: In developing countries, the complementary feeding period is critical to the growth of children, notably because of inappropriate complementary feeding practices. A longitudinal study was carried out in a food vulnerable area in Burkina Faso to better understand and describe these practices. METHODS: A cohort of 114 children was followed at the ages of 6, 9, 12, 15, 18, and 24 mo. At each visit details on the complementary foods (CF) were recorded and intakes were measured by direct weighing. RESULTS: At 6 mo of age all infants were breastfed and 61% were still breastfed at 24 mo. Infants not receiving any CF were 97% at enrollment, 53% at 9 mo, and 11% at 12 mo (mean age of introduction = 9.2 +/- 1.7 mo). Porridge was the type of CF introduced first (46%) but was of poor diversity; special dishes were less often given but did contain more numerous ingredients. However, less than half of the children received the recommended minimum of four different food groups/d before being 2 y old. At 12 mo and after, more than 75% of the children had at least 3 meals/d. Quantities of CF consumed increased from 133 +/- 121 g/d (19 +/- 17 g per kg of body weight/d) at 9 mo to 480 +/- 237 g/d (49 +/- 25 g/kg/d) at 24 mo (for breastfed children). CONCLUSION: Late introduction of CF and poor diversity of ingredients, more than quantity of food, were the main weaknesses observed in this context. At least part of these issues can be addressed through educational activities. PMID- 20579593 TI - Impact of probiotic supplementation on mortality of induced 1,2-dimethylhydrazine carcinogenesis in a mouse model. AB - RATIONALE: Probiotic bacterial strains have been increasingly used in clinical practice as many health benefits result from their use. However, severe side effects such as bacteremia and fungemia have been reported in inmunocompromised patients and those with chronic disease. OBJECTIVE: The purpose of this study was to report the impact of probiotic supplementation on the mortality of mice undergoing carcinogenesis induction with 1,2-dimethylhydrazine (DMH). METHODS: Two treatment protocols were used. In experiment 1, Lactobacillus delbrueckii UFV H2b20, Bifidobacterium animalis var. lactis Bb12, and Saccharomyces boulardii were added to the drinking water, to control mice and those undergoing injections of DMH daily. Probiotic supplementation was started 1 wk before and continued throughout the 6 wk of DMH injections. In experiment 2, the same probiotics were administered daily, except on the first day that DMH was administered. The mortality of these animals was recorded. Bacterial translocation was determined in mice in experiment 1. RESULTS: Groups with DMH-induced injury treated with lactobacilli, bifidobacteria, and the mixture of lactobacilli and bifidobacteria presented with 40%, 30%, and 60% mortality, respectively. Death happened mainly between 48 h and 72 h after the first injection of DMH. On the other hand, no mice in experiment 2 died during the study period. Bacteria were found to be translocated to mesenteric lymph nodes, spleen, and liver. CONCLUSION: Supplementation of L. delbrueckii UFV-H2b20 and B. animalis var. lactis Bb12 in mice with DMH-induced injury led to death in some animals. The results suggest that increased bacterial translocation was probably related to mortality. These findings are an alert to the potentially severe side effects associated with the use of probiotics under extremely stressful situations. PMID- 20579594 TI - Pediatric dermatology. PMID- 20579595 TI - Food allergy and atopic dermatitis: separating fact from fiction. AB - The relationship between food and atopic dermatitis (AD) is complex. A common misunderstanding is that food allergies have a significant impact on the course of AD, resulting in uncontrolled attempts at elimination diets and undertreatment of the skin itself. Studies have shown that only a small portion of cutaneous reactions to food in the form of late, eczematous eruptions will directly exacerbate AD in young infants who have moderate-to-severe AD. Given the low frequency of food allergies actually inducing flares of AD, the focus should return to appropriate skin therapy, and identification of true food allergies should be reserved for recalcitrant AD in children in whom the suspicion for food allergy is high. A different relationship between food and AD involves delaying or preventing AD in high-risk infants by exclusive breastfeeding during the first 4 months of life. Finally, the skin barrier defect in AD may allow for easier and earlier sensitization of food and airborne allergens; therefore, exposure of food proteins on AD skin may act as a risk factor for development of food allergies. PMID- 20579596 TI - Large congenital melanocytic nevi: associated risks and management considerations. AB - Large congenital melanocytic nevi (LCMN) in neonates can cause considerable concern for parents, family members, and physicians. A detailed understanding of the medical risks, including cutaneous melanoma (CM), extracutaneous melanoma (ECM), and neurocutaneous melanocytosis (NCM), as well as the psychological stress that these lesions can cause in patients, will guide informed management decisions as well as provide comfort to parents. Current data indicate that LCMN greater than 20 cm, and more likely greater than 40 to 60 cm, are the lesions at greatest risk for complications such as CM, ECM, and NCM. Additionally, lesions on the trunk are at greater risk for developing CM, and LCMN in association with numerous satellite nevi are at greatest risk for NCM. Individualized management plans, including clinical observation, magnetic resonance imaging (MRI), and possibly surgery should be based on the risk versus benefit ratio, taking into account the size of the LCMN, its location, the number of satellite nevi, symptoms, and numerous other factors which will be reviewed. This paper will provide a detailed analysis of the risks associated with LCMN, as well as a discussion regarding management and treatment options. PMID- 20579597 TI - Autoimmune blistering diseases in children. AB - Autoimmune blistering disorders comprise a series of conditions in which autoantibodies target components of the skin and mucous membranes, leading to blister and bullae formation. Most conditions in the spectrum of autoimmune blistering disorders are uncommonly seen in the pediatric population, even the most common ones, such as chronic bullous disease of childhood and dermatitis herpetiformis; however, they often come into the differential diagnosis of other more common pediatric entities. In addition, prompt recognition and treatment avoids unnecessary morbidity and improves ultimate outcome. PMID- 20579598 TI - Clinical update on graft-versus-host disease in children. AB - The last decade has yielded many significant advances in hematopoietic transplantation techniques, immunomodulatory prophylaxis, and diagnostic and treatment approaches to acute and chronic graft-versus-host disease (GVHD). Unfortunately, GVHD remains the cardinal complication in allogeneic hematopoietic stem cell transplantation, with significant associated rates of morbidity and mortality. In this review, we highlight the numerous strides that have been made in making hematopoietic transplantation more successful and provide an update on the clinical and histopathological features of both acute and chronic GVHD in the pediatric population. It is critical for dermatologists to be aware of the characteristic features of cutaneous acute and chronic GVHD and to remain up to date on the evolving spectrum of these conditions. We discuss 5 cases with clinico-pathologic correlation to illustrate the key concepts and principles underlying the diagnosis and management of both acute and chronic GVHD. PMID- 20579599 TI - Current management of infantile hemangiomas. AB - During the past several years, there have been new advancements in the management of infantile hemangiomas (IHs). In many patients, no treatment is ever necessary- because IHs are well known for their natural history of spontaneous involution. However, a significant minority of hemangiomas do require treatment. Moreover, they are very heterogeneous, making the decision of when, how, and why to intervene quite variable. The least common but most important rationale for intervention is the presence of a life- or function-threatening complication, where prompt therapeutic intervention is a necessity. A much more common scenario is ulceration, where appropriate management is needed to expedite healing and control pain. Increasingly, the life-altering aspects of hemangioma are being recognized as a rationale for treatment because permanent scarring and disfigurement can result even if involution is complete. Treatments for IHs currently include topical, intralesional, and systemic therapies. Laser and surgical modalities are also sometimes used depending on the clinical scenario. In the absence of rigorous evidence-based studies, clinicians must carefully weigh the risks and benefits of medical or surgical treatments versus observation alone in tailoring management to the specific clinical situation at hand. PMID- 20579600 TI - Phototherapy in pediatric patients: choosing the appropriate treatment option. AB - Phototherapeutic modalities, including narrowband-UVB, broadband-UVB, PUVA photochemotherapy, and excimer laser therapy are valuable tools that can be used for photoresponsive dermatoses in children. As a systematically safer alternative compared with internal agents, including the prebiologic and biological therapies, phototherapy should be considered a possible treatment option for children with diseases including psoriasis, atopic dermatitis, pityriasis lichenoides chronica, and vitiligo. PMID- 20579601 TI - Diagnosis and treatment of primary focal hyperhidrosis in children and adolescents. AB - Primary focal hyperhidrosis is a disorder of excessive sweating that occurs in the axillae, palms, soles, and craniofacial region in amounts greater than needed for thermal regulation. Although the etiology is unknown, this disorder can cause significant emotional and social distress. The focus of this paper is the diagnosis and treatment of primary focal hyperhidrosis in children and adolescents. PMID- 20579602 TI - Genetics for the practicing dermatologist. AB - In the era of robust genome sequencing, a working understanding of genetics has become important for the clinician. For the dermatologist, understanding the flow of genetic information from genotype to phenotype can aid in the delivery of effective patient care. In this article, we will review concepts in genetics and the human genome and how they contribute to clinical dermatology. PMID- 20579603 TI - Understanding and improving treatment adherence in pediatric patients. AB - Many common skin diseases of children are easily diagnosed by dermatologists and have straightforward treatments. Nevertheless, sometimes these conditions are frustratingly difficult for both patients and physicians to control. Poor adherence to treatment may be the underlying cause of poor outcomes in many situations. Studies of pediatric patients' use of medication show poor use across a broad array of medical illnesses. Studies of adherence in children with acne and atopic dermatitis show similar findings. The reasons for poor adherence likely vary across the pediatric age range, with fears of side effects being pre eminent in the care of infants and interpersonal interactions playing a greater role in adolescents. By recognizing the major hurdles to adherence across the different ages, dermatologists may be better able to tailor interventions to improve the outcomes of children with skin disease. PMID- 20579604 TI - Pediatric urology. PMID- 20579605 TI - SNE: a place where research and practice meet. PMID- 20579606 TI - Mealtime perspectives. PMID- 20579607 TI - Gender perspectives on adolescent eating behaviors: a study on the eating attitudes and behaviors of junior secondary students in Hong Kong. AB - OBJECTIVE: This research aimed to investigate the eating attitudes and behaviors of junior secondary students in Hong Kong, with a specific focus on possible gender differences. DESIGN: A survey was conducted in 2005 to solicit data about participants' food knowledge, eating attitudes and behavior, perceptions of cooking skills and body weight, and related factors influencing food choice. SETTING: Twenty-three secondary schools located in different district areas of Hong Kong. PARTICIPANTS: The sample was composed of 836 students (41% male, 59% female) aged 11-18 years selected by random sampling. ANALYSIS: Cross-tabulation analyses were used to compare the responses by gender. RESULTS: Regardless of gender, less than half of the sample ate breakfast every day, and their consumption of fruits and vegetables was below recommended daily intakes. No significant differences were observed between respondents' eating habits and levels of food knowledge.Female students were more weight conscious than male students. Dissatisfaction about body weight was common among normal and underweight students. Cooking skills were generally valued as important life skills by both genders, though cooking skills were seen to be more relevant for girls. CONCLUSIONS AND IMPLICATIONS: School nutrition education in Hong Kong should be designed to appeal to boys as well as girls, and effective implementation of nutrition education programs should inculcate healthful eating habits and sound cooking skills and address the needs of students with reference to gender differences. A more diversified approach could be employed through formal and informal curricula, prioritizing cooking skills and food advertising literacy in the curriculum. PMID- 20579609 TI - "Are you done?" Child care providers' verbal communication at mealtimes that reinforce or hinder children's internal cues of hunger and satiation. AB - OBJECTIVE: To explore the verbal communication of child care providers regarding preschool children's internal and non-internal hunger and satiation cues. METHODS: Video observation transcripts of Head Start staff (n=29) at licensed child care centers in Colorado, Idaho, and Nevada were analyzed for common themes. RESULTS: Adults' verbal communication with children at mealtimes emphasized non-internal cues: (1) cueing children to amounts without referencing children's internal cues; (2) meal termination time; (3) asking children if they wanted more without referencing their internal cues; (4) asking children if they were done without referencing their internal cues; (5) telling children to take, try, eat, or finish food; (6) praising children for eating; and (7) telling children about food being good for you. Adults demonstrated an overriding effort to get children to eat. CONCLUSIONS AND IMPLICATIONS: Training needs to be developed that gives specifics on verbally cueing young children to their internal hunger and satiation cues. PMID- 20579608 TI - Food allergy educational needs of pediatric dietitians: a survey by the Consortium of Food Allergy Research. AB - OBJECTIVE: To determine pediatric dietitians' self-reported proficiency, educational needs, and preferences regarding food allergy (FA) management. DESIGN AND SETTING: An Internet-based, anonymous survey was distributed to the Pediatric Nutrition Practice Group (PNPG) of the American Dietetic Association. PARTICIPANTS: Respondents (n = 311) were registered dietitians and members of the PNPG. ANALYSIS: Results are presented using descriptive statistics. Chi-square tests were applied for subgroup analyses. Percentage responses were calculated per question based on the number of respondents answering the question. RESULTS: On a 4-point scale of proficiency ("high," "moderate," "low," and "none"), respondents primarily rated themselves "moderate" for educating families, creating diets, and evaluating safe food items, and "low" for creating diagnostic food challenges. Education was primarily self-taught (75%). Preferences for future resources included handbooks (77%) and Web-based instructional programs (53%). On a 4-point scale ("very" to "not at all" needed) among practices that included >10% patients with FA, ratings of "very" were defined as need resources to update FA knowledge (87%) and need for a FA "tool kit" (84%). CONCLUSIONS AND IMPLICATIONS: Pediatric dietitians manage FA for a substantial patient base although their self-reported proficiency is overall only moderate. Dietitians would prefer and likely benefit from Internet-accessible management handbooks and patient handouts. PMID- 20579610 TI - Mississippi elementary school teachers' perspectives on providing nutrition competencies under the framework of their school wellness policy. AB - OBJECTIVE: Identify elementary teachers' implementation of nutrition competencies as part of their school wellness policies (SWP) guided by Organizational Change Theory (OCT) constructs. METHODS: A 32-item, cross-sectional survey was distributed through a Web link e-mailed to teachers in Mississippi public elementary schools. Response rate was 34% (n = 947) from 30 schools. Principal component factor analysis for inter-item correlations and theoretical fit to OCT was used with internal consistency reliability coefficients determined using Cronbach's alpha for Likert-type scales. RESULTS: A majority of teachers (85.5%) favors their SWPs and has transitioned through the unfreezing stage. Lack of teacher input, time, resources, and recognition for providing nutrition education reflects that teachers do not have support for transitioning through the moving stage. CONCLUSIONS AND IMPLICATIONS: Use of evaluation tools to facilitate teachers' progress through the moving stage into the refreezing stage would be advantageous in supporting organizational change as school administrations implement SWPs. PMID- 20579611 TI - Cognitive testing with female nutrition and education assistance program participants informs validity of the Satter eating competence inventory. AB - OBJECTIVE: Examine the validity of a self-report measure of eating competence with low-income women. METHODS: Twenty-five females (18-49 years old) recruited from low-income venues in Pennsylvania completed cognitive testing through an iterative interview process. Respondents' oral responses were compared to researchers' intended meaning of ecSatter Inventory (ecSI) items; responses were mapped to evaluate the similarity between respondents' internally generated answers and their ecSI choices for survey items; and scored responses were compared among participants. RESULTS: Interview findings provided a rationale for modifying the ecSI prior to use with low-income women. Four items were misinterpreted for various reasons, including problems with clarity and wording. The modified ecSI, termed the ecSatter Inventory for Low-Income (ecSI/LI), was comprehended as intended by researchers. Congruence of cognitive responses and ecS/LI scores further supported the instrument's validity. CONCLUSIONS AND IMPLICATIONS: Cognitive testing resulted in the development of an instrument to measure eating competence in low-income adults. The ecSI/LI requires validation with a large, heterogeneous low-income sample. PMID- 20579612 TI - Teaching cross-cultural entrepreneurial nutrition. PMID- 20579613 TI - How food safe is your home kitchen? A self-directed home kitchen audit. PMID- 20579615 TI - Computed tomography of septal defects. AB - Septal defects are common congenital cardiac anomalies that may present in adulthood. Although echocardiography and magnetic resonance imaging are most frequently used to assess for and evaluate septal defects, multidetector computed tomography (CT), with its high spatial and temporal resolutions, multiplanar reconstruction capabilities, and wide field of view, is an excellent tool for detection and characterization of septal defects and for identification of associated anomalies of the heart and pulmonary vasculature. Knowledge of the CT appearances of septal defects and their respective associated abnormalities is critical for accurate reporting as well as for providing information for planning of surgical or percutaneous therapy. In this pictorial review, the CT appearances of various atrial and ventricular septal defects and associated shunts are described and illustrated. PMID- 20579616 TI - Left coronary artery from the right coronary sinus: what can CT angiography tell us? PMID- 20579618 TI - CT imaging of myocardial infarction: time for another step forward. PMID- 20579617 TI - Comparison of postprocessing techniques for the detection of perfusion defects by cardiac computed tomography in patients presenting with acute ST-segment elevation myocardial infarction. AB - BACKGROUND: Despite rapid advances in cardiac computed tomography (CT), a strategy for optimal visualization of perfusion abnormalities on CT has yet to be validated. OBJECTIVE: We evaluated the performance of several postprocessing techniques of source data sets to detect and characterize perfusion defects in acute myocardial infarctions with cardiac CT. METHODS: Twenty-one subjects (18 men; 60 +/- 13 years) that were successfully treated with percutaneous coronary intervention for ST-segment myocardial infarction underwent 64-slice cardiac CT and 1.5 Tesla cardiac magnetic resonance imaging (MRI) scans after revascularization. Delayed enhancement MR images were analyzed to identify the location of infarcted myocardium. Contiguous short-axis images of the left ventricular myocardium were created from the CT source images with 0.75-mm multiplanar reconstruction (MPR), 5-mm MPR, 5-mm maximal intensity projection (MIP), and 5-mm minimum intensity projection (MinIP) techniques. Segments already confirmed to contain infarction by MRI were then evaluated qualitatively and quantitatively with CT. RESULTS: Overall, 143 myocardial segments were analyzed. On qualitative analysis, the MinIP and thick MPR techniques had greater visibility and definition than the thin MPR and MIP techniques (P < 0.001). On quantitative analysis, the absolute difference in Hounsfield unit attenuation between normal and infarcted segments was significantly greater for the MinIP (65.4 Hounsfield unit [HU]) and thin MPR (61.2 HU) techniques. However, the relative difference in Hounsfield unit attenuation was significantly greatest for the MinIP technique alone (95%; P < 0.001). Contrast to noise was greatest for the MinIP (4.2) and thick MPR (4.1) techniques (P < 0.001). CONCLUSION: The results of our current investigation found that MinIP and thick MPR detected infarcted myocardium with greater visibility and definition than MIP and thin MPR. PMID- 20579619 TI - Calcified right intraventricular thrombus in a patient with systemic lupus erythematous and antiphospholipid syndrome. AB - A 37-year-old patient with known systemic lupus erythematous, antiphospholipid syndrome and previous pulmonary embolism presented with non-ST elevation myocardial infarction while on adequate anticoagulation therapy. The patient was further evaluated with cardiac computed tomography. A small diagonal branch occlusion was the only coronary lesion present. A partially calcified right ventricular thrombus was incidentally found. Because of the small vessel size, cardiac catheterization was deemed unnecessary, and the patient was discharged with adjustment of immunosuppressive therapy and anticoagulation. PMID- 20579620 TI - Coronary arterial microfistulae: a CT coronary angiography perspective. AB - Coronary arterial microfistulae are abnormal connections between one or multiple coronary arteries and any cardiac chamber, vein, or thoracic vessel. They comprise a subsection of coronary fistulas where the abnormal connections are diffuse, as opposed to the larger, more common single vessel varieties. Most of these anomalies are detected incidentally on catheter angiography; however, we present this anomaly as a case report from the perspective of CT coronary angiography. PMID- 20579621 TI - Evaluation of cor triatriatum dexter with use of 64-slice multidetector computed tomography. AB - Cor triatriatum dexter, a rare condition in which the right atrium is divided by an anomalous membrane, is shown with cardiac CT, magnetic resonance imaging and direct surgical visualization. PMID- 20579622 TI - Giant left ventricular pseudoaneurysm. AB - Left ventricular (LV) pseudoaneurysm (PS) is an uncommon, often fatal complication associated with myocardial infarction, cardiothoracic surgery, trauma, and, rarely, infective endocarditis. A 28-year-old man with prior history of bioprosthetic mitral valve replacement presented with congestive heart failure and bacteremia with Abiotrophia granulitica. Transesophageal echocardiogram showed bioprosthesis dysfunction, large vegetations, mitral regurgitation, and probable PS. Cardiac and chest CT confirmed a PS communicating with the left ventricle Patient had pulseless electrical activity and died. Autopsy showed a giant PS with layered thrombus and pseudo-endothelialized cavity. Our case highlights the importance of multimodality imaging as an important tool in management of PS. PMID- 20579623 TI - President's page: prospective and retrospective preeminence: what is right about coronary CT. PMID- 20579624 TI - Dimension-based attention modulates feed-forward visual processing. PMID- 20579625 TI - Population genetic structure of the people of Qatar. AB - People of the Qatar peninsula represent a relatively recent founding by a small number of families from three tribes of the Arabian Peninsula, Persia, and Oman, with indications of African admixture. To assess the roles of both this founding effect and the customary first-cousin marriages among the ancestral Islamic populations in Qatar's population genetic structure, we obtained and genotyped with Affymetrix 500k SNP arrays DNA samples from 168 self-reported Qatari nationals sampled from Doha, Qatar. Principal components analysis was performed along with samples from the Human Genetic Diversity Project data set, revealing three clear clusters of genotypes whose proximity to other human population samples is consistent with Arabian origin, a more eastern or Persian origin, and individuals with African admixture. The extent of linkage disequilibrium (LD) is greater than that of African populations, and runs of homozygosity in some individuals reflect substantial consanguinity. However, the variance in runs of homozygosity is exceptionally high, and the degree of identity-by-descent sharing generally appears to be lower than expected for a population in which nearly half of marriages are between first cousins. Despite the fact that the SNPs of the Affymetrix 500k chip were ascertained with a bias toward SNPs common in Europeans, the data strongly support the notion that the Qatari population could provide a valuable resource for the mapping of genes associated with complex disorders and that tests of pairwise interactions are particularly empowered by populations with elevated LD like the Qatari. PMID- 20579626 TI - Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. AB - Osteogenesis imperfecta, or "brittle bone disease," is a type I collagen-related condition associated with osteoporosis and increased risk of bone fractures. Using a combination of homozygosity mapping and candidate gene approach, we have identified a homozygous single base pair deletion (c.1052delA) in SP7/Osterix (OSX) in an Egyptian child with recessive osteogenesis imperfecta. The clinical findings from this patient include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing, and white sclera. OSX encodes a transcription factor containing three Cys2-His2 zinc-finger DNA-binding domains at its C terminus, which, in mice, has been shown to be essential for bone formation. The frameshift caused by the c.1052delA deletion removes the last 81 amino acids of the protein, including the third zinc-finger motif. This finding adds another locus to the spectrum of genes associated with osteogenesis imperfecta and reveals that SP7/OSX also plays a key role in human bone development. PMID- 20579628 TI - Polyethylene glycol hydrogel polymer sealant for closure of sutureless sclerotomies: a histologic study. AB - PURPOSE: To evaluate a polyethylene glycol-based hydrogel bandage for its ability to secure sutureless pars plana vitrectomy sclerotomies. DESIGN: Laboratory investigation. METHODS: Twenty-gauge (20-G) and twenty-three gauge (23-G) sclerotomies were constructed in human cadaveric eyes. A total of 24 sclerotomies were constructed in 6 eyes. Four sclerotomies per eye were constructed. Two were straight 20-G incisions, of which 1 was sutured and 1 was covered with the bandage. The other 2 were 23-G beveled incisions, of which 1 was left bare and the other was closed with the hydrogel bandage. India ink was applied over the sclerotomy sites while the intraocular pressure (IOP) was varied. The presence of India ink particles along incisions was evaluated by histologic analysis. RESULTS: The hydrogel bandage prevented the entry of ink particles in all covered incisions after IOP modulation and incision manipulation. One 20-G sutured incision showed partial ink ingress. Four uncovered 23-G incisions showed the presence of ink within the inner aspect of the incisions (P = .0455 relative to 23-G sealed incisions). Twenty-two out of 24 incisions were evaluated, as 2 incisions could not be identified on histologic analysis. CONCLUSIONS: The use of a hydrogel bandage to close sutureless sclerotomies is a practical alternative to sutures. Closure of sutureless sclerotomies may reduce the entry of ocular surface fluid into these incisions as well as prevent leakage of intraocular fluid in the immediate postoperative period. Incision closure may reduce the incidence of postoperative endophthalmitis and hypotony in sutureless vitreous surgery. PMID- 20579627 TI - X-linked cone dystrophy caused by mutation of the red and green cone opsins. AB - X-linked cone and cone-rod dystrophies (XLCOD and XLCORD) are a heterogeneous group of progressive disorders that solely or primarily affect cone photoreceptors. Mutations in exon ORF15 of the RPGR gene are the most common underlying cause. In a previous study, we excluded RPGR exon ORF15 in some families with XLCOD. Here, we report genetic mapping of XLCOD to Xq26.1-qter. A significant LOD score was detected with marker DXS8045 (Z(max) = 2.41 [theta = 0.0]). The disease locus encompasses the cone opsin gene array on Xq28. Analysis of the array revealed a missense mutation (c. 529T>C [p. W177R]) in exon 3 of both the long-wavelength-sensitive (LW, red) and medium-wavelength-sensitive (MW, green) cone opsin genes that segregated with disease. Both exon 3 sequences were identical and were derived from the MW gene as a result of gene conversion. The amino acid W177 is highly conserved in visual and nonvisual opsins across species. We show that W177R in MW opsin and the equivalent W161R mutation in rod opsin result in protein misfolding and retention in the endoplasmic reticulum. We also demonstrate that W177R misfolding, unlike the P23H mutation in rod opsin that causes retinitis pigmentosa, is not rescued by treatment with the pharmacological chaperone 9-cis-retinal. Mutations in the LW/MW cone opsin gene array can, therefore, lead to a spectrum of disease, ranging from color blindness to progressive cone dystrophy (XLCOD5). PMID- 20579629 TI - Analysis of retinal flecks in fundus flavimaculatus using high-definition spectral-domain optical coherence tomography. AB - PURPOSE: To assess morphologic changes associated with retinal flecks in fundus flavimaculatus using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Observational case series. METHODS: Simultaneous recordings of SD-OCT and confocal scanning laser ophthalmoscope (cSLO) fundus autofluorescence images were obtained in fundus flavimaculatus patients. Morphologic aspects of the retinal flecks were analyzed and classified. RESULTS: Thirty-one eyes of 17 consecutive patients (8 male, 9 female; mean age 47.9 +/- 17.1 years) were included for analysis. SD-OCT revealed 5 distinct types of lesions. Group A lesions were limited to the outer segment (OS) of the photoreceptors, the retinal pigment epithelium (RPE) interdigitations, and the RPE/Bruch membrane complex. Group B showed a protrusion of the hyper-reflective material through the interface of inner segment (IS)/OS of the photoreceptors up to the external limiting membrane. A further protrusion of the hyper-reflective material into the outer nuclear layer was seen in group C lesions. Group D lesions were characterized by an accumulation of the hyper-reflective material limited to the outer nuclear layer. Type E lesions can be described as drusen-like retinal pigment detachments. No significant correlation between the different types of flecks and visual acuity was observed (P > .05). CONCLUSIONS: SD-OCT allows one to distinguish at least 5 different types of lesions associated with retinal flecks in fundus flavimaculatus. The ability to characterize the different types of flecks and to analyze the photoreceptor layers surrounding these lesions suggests that SD-OCT might have a potential clinical role in the evaluation and follow-up of the structural changes in fundus flavimaculatus. PMID- 20579630 TI - The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty. AB - PURPOSE: To analyze factors influencing corneal graft re-epithelialization after penetrating keratoplasty (PK) and evaluate the effect of topical autologous serum in promoting graft re-epithelialization. DESIGN: Prospective interventional study. METHODS: We analyzed 165 eyes of 165 patients who underwent PK between January 1, 2005 and December 31, 2007. Patients were divided into 2 groups according to routine use or non-use of postoperative 20% topical autologous serum. Postoperative slit-lamp examination after fluorescein staining was performed, and graft re-epithelialization time was recorded. Recipient/donor characteristics, surgical variables, and topical use of autologous serum were analyzed for their effects on post-PK graft re-epithelialization. Statistical analysis was performed by univariate and multivariate regression analysis using the ordinal logistic fit model to assess the potential risk factors influencing graft re-epithelialization after PK. RESULTS: In univariate analysis, diabetes mellitus (DM), longer death-to-storage time and death-to-surgery time of the donor, and larger recipient size significantly delayed graft re-epithelialization (P < .05). Use of autologous serum significantly expedited graft re epithelialization (P = .004). In multiple regression analysis, only DM in the recipient (odds ratio [OR] = 5.10, P < .001), postoperative use of autologous serum (OR = 0.54, P = .046), and larger graft size (OR = 4.44, P < .001) influenced graft re-epithelialization. The beneficial and healing effect of autologous serum is particularly significant in diabetic recipients and larger grafts. CONCLUSIONS: Several factors may influence graft re-epithelialization after PK. Graft re-epithelialization time was longer in diabetic recipients and larger grafts. Use of autologous serum may be a beneficial strategy in these patients with potentially delayed epithelial healing. PMID- 20579631 TI - Retrocorneal membranes: a comparative immunohistochemical analysis of keratocytic, endothelial, and epithelial origins. AB - PURPOSE: To determine through the use of immunohistochemistry the origins of retrocorneal cellular and fibrillar membranes. DESIGN: Retrospective, clinicopathologic study using surgically removed human corneal tissues. METHODS: Clinical records of patients' ocular diseases and surgical procedures were reviewed. Immunohistochemical staining was performed on 5 enucleated control globes, 32 penetrating keratoplasty specimens, and 6 Descemet stripping endothelial keratoplasty specimens to analyze: (1) the normal corneal epithelium, stroma, and endothelium; and (2) stromal scars, endothelial abnormalities, and retrocorneal membranes. Paraffin sections were stained with hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome methods, and immunohistochemical analyses were performed with commonly available monoclonal and polyclonal antibodies for various cytokeratins (CKs), CD34, alpha-smooth muscle actin (SMA), and vimentin. RESULTS: Five subtypes among 28 retrocorneal membranes were characterized. Twelve fibrous (keratocytic) membranes of stromal origin had coarse collagen and immunostained negatively for all CKs, but strongly for vimentin and alpha-SMA, the last the only marker of diagnostic value. Nine metaplastic endothelium-derived membranes produced delicate collagenous matrices and immunoreacted with CK7, vimentin, and alpha-SMA. Two epithelial multilaminar or monolaminar membranes reacted with CK cocktail and wide-spectrum CK, mildly with CK7 (not observed in orthotopic surface epithelium), and negatively for alpha-SMA and vimentin. The final 2 categories were indeterminate or non immunoreactive (3 specimens) and mixed (2 specimens). CONCLUSIONS: Immunohistochemistry can diagnose retrocorneal membranes of different provenances reliably in most cases. Clinical correlations established that these membranes develop after serious inflammatory disorders, prolonged wounding or ulcerations, and multiple surgeries (an average of 3.4 per patient). PMID- 20579632 TI - Early vitrectomy for vitreous hemorrhage associated with retinal tears. AB - PURPOSE: To evaluate outcome of early surgery in vitreous hemorrhage, presumably associated with retinal tears. DESIGN: Retrospective, noncomparative interventional case series. METHODS: We included 40 consecutive cases in 39 patients treated with early vitrectomy for vitreous hemorrhage. Main outcome measures were incidence of tears identified preoperatively and intraoperatively, visual acuity, and complications. RESULTS: Vitrectomy took place after a mean delay of 2.7 days after presentation. A total of 69 tears were found in 40 eyes; 53.7% of tears were identified preoperatively by funduscopy or ultrasound (U/S) and the remaining 46.3% of tears were only identified during vitrectomy. Visual acuity improved significantly from 1/60 to 0.8. The sensitivity of U/S tear detection was 55.9%. A history of predisposing factors was not related to the risk of presence of unsupported tears. In 2 cases a retinal detachment developed between the U/S evaluation and vitrectomy. Postoperative complications were cataract (30%), macular pucker (2.5%), and retinal detachment (5.0%). CONCLUSIONS: Our findings illustrate the potential dangers of a conservative approach to vitreous hemorrhage and show that early vitrectomy has good outcome with acceptable complication rates. Prospective studies on optimal treatment of vitreous hemorrhage associated with tears are needed. PMID- 20579634 TI - Memory specificity as a risk factor for suicidality in non-affective psychosis: the ability to recall specific autobiographical memories is related to greater suicidality. AB - A difficulty in recalling specific autobiographical memories has been noted as a risk factor for suicidal behaviour. However, the relationship between memory specificity and suicide has not previously been investigated in those with non affective psychosis. It was predicted that in this group, more specific memory recall would be associated with an increased risk of suicide. This is because such specific memories are likely to be associated with greater levels of distress and negative affect than less specific memories. This prediction contradicts the prevailing belief that lower memory specificity is associated with greater suicidality. Sixty participants with schizophrenia spectrum disorders were recruited, 40 of whom reported past suicide attempts. Analyses showed suicide attempters recalled a greater proportion of specific memories, whilst controlling for trait anxiety and depressive symptoms. These results supported the main hypothesis, and suggest non-specific memory may have adaptive qualities in individuals with psychosis. PMID- 20579633 TI - Dialectical behavior therapy skills use as a mediator and outcome of treatment for borderline personality disorder. AB - A central component of Dialectical Behavior Therapy (DBT) is the teaching of specific behavioral skills with the aim of helping individuals with Borderline Personality Disorder (BPD) replace maladaptive behaviors with skillful behavior. Although existing evidence indirectly supports this proposed mechanism of action, no study to date has directly tested it. Therefore, we examined the skills use of 108 women with BPD participating in one of three randomized control trials throughout one year of treatment and four months of follow-up. Using a hierarchical linear modeling approach we found that although all participants reported using some DBT skills before treatment started, participants treated with DBT reported using three times more skills at the end of treatment than participants treated with a control treatment. Significant mediation effects also indicated that DBT skills use fully mediated the decrease in suicide attempts and depression and the increase in control of anger over time. DBT skills use also partially mediated the decrease of nonsuicidal self-injury over time. Anger suppression and expression were not mediated. This study is the first to clearly support the skills deficit model for BPD by indicating that increasing skills use is a mechanism of change for suicidal behavior, depression, and anger control. PMID- 20579635 TI - Enzymatic synthesis of L-DOPA alpha-glycosides by reaction with sucrose catalyzed by four different glucansucrases from four strains of Leuconostoc mesenteroides. AB - L-DOPA alpha-glycosides were synthesized by reaction of L-DOPA with sucrose, catalyzed by four different glucansucrases from Leuconostoc mesenteroides B 512FMC, B-742CB, B-1299A, and B-1355C. The glucansucrases catalyzed the transfer of d-glucose from sucrose to the phenolic hydroxyl position-3 and -4 of L-DOPA. The glycosides were fractionated and purified by Bio-Gel P-2 column chromatography, and the structures were determined by (1)H NMR spectroscopy. The major glycoside was 4-O-alpha-d-glucopyranosyl L-DOPA, and the minor glycoside was 3-O-alpha-D-glucopyranosyl L-DOPA. The two glycosides were formed by all four of the glucansucrases. The ratio of the 4-O-alpha-glycoside to the 3-O-alpha glycoside produced by the B-512FMC dextransucrase was higher than that for the other three glucansucrases. The glycosylation of L-DOPA significantly reduced the oxidation of the phenolic hydroxyl groups, which prevents their methylation, potentially increasing the use of L-DOPA in the treatment of Parkinson's disease. The use of one enzyme, glucansucrase, and sucrose as the D-glucosyl donor makes the synthesis considerably simpler and cheaper than the formerly published procedure using cyclomaltodextrin and cyclomaltodextrin glucanyltransferase, followed by glucoamylase, and beta-amylase hydrolysis. PMID- 20579636 TI - Regioselective [3+2] cycloaddition of chalcones with a sugar azide: easy access to 1-(5-deoxy-D-xylofuranos-5-yl)-4,5-disubstituted-1H-1,2,3-triazoles. AB - [3+2] Cycloaddition of 5-azido-5-deoxy-1,2-O-isopropylidene-alpha-d-xylofuranose with 1,3-diphenyl-prop-3-enones, followed by oxidation of the intermediate triazolines in a tandem manner, led to the regioselective formation of 4-benzoyl 1-(5-deoxy-1,2-O-isopropylidene-alpha-d-xylofuranos-5-yl)-5-phenyl-1H-1,2,3 triazoles in moderate to good yields. PMID- 20579637 TI - Argentina's early contributions to the understanding of frontotemporal lobar degeneration. AB - Over a 100 years have passed since Pick's description of what is now termed frontotemporal lobar degeneration (FTLD). FTLD is a topic of intense current research interest yet some relevant contributions by non-English speaking authors have received little attention, which makes the history of FTLD research incomplete. In the hopes of filling some of the gaps in the history of FTLD research, the present article introduces fundamental work carried out in Argentina during the first half of the 20th century by Christfried Jakob and Braulio A. Moyano. Jakob's neurophilosophy, as well as his empirical descriptions on dementia and theoretic insights into the role of the frontal lobes are highlighted. Moyano's works on frontotemporal dementia (FTD), specifically concerning language deficits and the concept of focal pathology in Alzheimer disease presenting with progressive aphasia are introduced. These early contributions are examined in the light of the current knowledge on FTLD, highlighting some of the authors' early original contributions, as well as their misconceptions. These authors remain largely unknown despite the fact that their contributions were fundamental in kindling interest in behavioral neurology in Latin America, which continues to this day. PMID- 20579638 TI - OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling. AB - The 2-oxoglutarate and iron dependent dioxygenase family are crucial for cellular adaptation to changes in oxygen concentration. We found that cells with OGFOD1 gene silencing in this family showed resistance to cell death under ischemia, and cDNA microarray analysis of OGFOD1 knockout human cells revealed downregulation of ATPAF1. Although reintroduction of the OGFOD1 wild-type gene to OGFOD1 KO cells restored ATPAF1 mRNA levels, the catalytically inactive OGFOD1 mutants did not. Furthermore, introduction of ATPAF1 gene to OGFOD1 KO cells induced ischemic cell death. Thus, OGFOD1 plays an important role in ischemic cell survival and an OGFOD1 iron binding residue is required for ATPAF1 gene expression. PMID- 20579639 TI - A case of severe asthenozoospermia: a novel sperm tail defect of possible genetic origin identified by electron microscopy and immunocytochemistry. AB - OBJECTIVE: To characterize a novel flagellar defect involving 98% of sperm tails. DESIGN: Case report. SETTING: Interdepartmental Centre for Research and Therapy of Male Infertility, Siena, Italy. PATIENT(S): A 45-year-old infertile man with severe asthenozoospermia. INTERVENTION(S): Family history, physical examination, hormonal analysis, microbial assays, semen analysis, transmission and scanning electron microscopy, tubulin distribution investigated by immunocytochemistry, fluorescence in situ hybridization (FISH) for chromosomes 9, 16, 18, X, and Y. MAIN OUTCOME MEASURE(S): Flagellar abnormalities detected by microscopical methods. RESULT(S): An apparent heterogeneity was observed: extremely elongated tails prone to ruptures; coiled tails at different levels with a strongly rolled axoneme or with a curl in the final flagellar segment; and V-shaped, isolated, bent tails. Transmission electron microscopy revealed the presence of normal heads, disorganized flagellar structures, and dynein deficiency. The FISH analysis was normal. CONCLUSION(S): We report a new sperm defect, characterized by abnormal elongation of the tail, which was prone to ruptures at different levels, concomitant with coiled tails, which were impossible to measure in length. This defect remained constant in different examined ejaculates and applied to the entire sperm population of a sterile man, the son of first-degree cousins, indicating a potential genetic origin. PMID- 20579640 TI - Racial variation in tubal sterilization rates: role of patient-level factors. AB - OBJECTIVE: To assess racial differences in attitudes and knowledge about sterilization. DESIGN: Cross-sectional survey. SETTING: Questionnaires were mailed to participants' home addresses. PATIENT(S): One hundred ninety-three women, aged 18-45, who had undergone tubal sterilization. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Attitudes and knowledge about tubal sterilization and awareness of contraceptive alternatives. RESULT(S): We received 193 completed surveys (64% response rate). African American (AA) woman were more likely to have a family member who had undergone tubal sterilization, to report that their mothers influenced their sterilization decisions, and to report that prior unintended pregnancy and desire to avoid insertion of a foreign object were very important factors in their decision to choose sterilization over other methods. Compared with white women, AA women more often thought that sterilization reversal could easily restore fertility (62% vs. 36%); that a woman's sterilization would reverse itself after 5 years (60% vs. 23%); and that a man cannot ejaculate after vasectomy (38% vs. 13%). Fewer AA women had ever heard of intrauterine contraception (90% vs. 98%). Racial differences in knowledge remained statistically significant after adjusting for socioeconomic confounders. CONCLUSION(S): Misinformation about sterilization and limited awareness of contraceptive alternatives among AA women may contribute to racial disparities in tubal sterilization rates. PMID- 20579641 TI - The use of arrays in preimplantation genetic diagnosis and screening. AB - BACKGROUND: In preimplantation genetic diagnosis (PGD), polymerase chain reaction has been used to detect monogenic disorders, and in PGD/preimplantation genetic screening (PGS), fluorescence in situ hybridization (FISH) has been used to analyze chromosomes. Ten randomized controlled trials (RCTs) using FISH-based PGS on cleavage-stage embryos and one on blastocyst-stage embryos have shown that PGS does not increase delivery rates. Is the failure of PGS due to a fundamental flaw in the idea, or are the techniques that are being used unable to overcome their own, inherent flaws? Array-based technology allows for analysis of all of the chromosomes. Two types of arrays are being developed for use in PGD; array comparative genomic hybridization (aCGH) and single nucleotide polymorphism-based (SNP) arrays. Each array can determine the number of chromosomes, however, SNP based arrays can also be used to haplotype the sample. OBJECTIVE(S): To describe aCGH and SNP array technology and make suggestions for the future use of arrays in PGD and PGS. CONCLUSION(S): If array-based testing is going to prove useful, three steps need to be taken: [1] Validation of the array platform on appropriate cell and tissue samples to allow for reliable testing, even at the single-cell level; [2] deciding which embryo stage is the best for biopsy: polar body, cleavage, or blastocyst stage; [3] performing RCTs to show improvement in delivery rates. If RCTs are able to show that array-based testing at the optimal stage for embryo biopsy increases delivery rates, this will be a major step forward for assisted reproductive technology patients around the world. PMID- 20579642 TI - Aromatase inhibitors in recurrent ovarian endometriomas: report of five cases with literature review. AB - OBJECTIVE: To determine the role of the aromatase inhibitor letrozole in the treatment of recurrent ovarian endometrioma cases. DESIGN: Nonrandomized proof of concept study. SETTINGS: Outpatient tertiary-care center. PATIENT(S): Five premenopausal patients with documented ovarian endometriomas and chronic pelvic pain, all of whom were previously treated with surgery and medicine with unsatisfactory results. INTERVENTION(S): Ovarian endometriomas were diagnosed by biopsy after laparoscopic ovarian cystectomy and subsequently treated with hormones. After a 6-month washout of endometriosis hormone therapies, women took letrozole (2.5 mg), one tablet of 0.15 mg of desogestrel, and 0.03 mg of ethinyl estradiol, calcium (1,200 mg), and vitamin D3 (800 IU) daily for 6 months. MAIN OUTCOME MEASURE(S): Size of endometriomas (monitored by ultrasound), assessment of pelvic pain (by visual analog scale), and bone density (DEXA scan). RESULT(S): Disappearance of ovarian endometrioma and reduction in pelvic pain in all cases at the end of 6 months. The size of ovarian endometriomas was reduced after 3 months. Pain scores decreased only after 1 month of treatment and continued decreasing in each treatment month. Overall, no significant change in bone density was detected. CONCLUSION(S): Letrozole given with combined pills achieved complete regression of recurrent endometriotic cysts and pain relief in all cases. PMID- 20579643 TI - Comparing high-sensitivity C-reactive protein (hs-CRP) with CRP as a soluble serum marker for the diagnosis of women with endometriosis. PMID- 20579644 TI - Hirsutism scoring in polycystic ovary syndrome: concordance between clinicians' and patients' self-scoring. AB - In a clinical series of 68 women with polycystic ovary syndrome in which the reason for consultation was hirsutism, the mean (standard error of the mean) hirsutism score of the modified Ferriman-Gallwey method was 15.1 (6.8), compared with 12.0 (4.4) for clinicians' scoring. In the multivariable analysis, clinicians' scoring of hirsutism was the only independent variable significantly associated with increased testosterone free index levels. PMID- 20579645 TI - 2009 H1N1 influenza prevention and treatment: counseling infertility patients. AB - It is known that pregnant women are at high risk for complications from the 2009 H1N1 influenza virus. Reproductive endocrinologists often have the opportunity to evaluate patients before conception and are able to counsel them before they become part of this high-risk obstetrics group. The 2009 H1N1 vaccine data and the current recommendations by the Centers for Disease Control and Prevention, American College of Obstetrics and Gynecology, and American Society of Reproductive Medicine are discussed. There is universal agreement in recommending vaccination for all pregnant women and all women attempting conception. Patients should be counseled regarding the vaccine and consider delaying conception until the immunization has been received. PMID- 20579647 TI - In vivo visualization of trophozoites in patients with amoebic colitis by using a newly developed endocytoscope. AB - BACKGROUND: The endocytoscopy system (ECS) is a new method to provide real-time super-magnifying microscopic imaging in vivo. Routine diagnosis of amebic colitis requires multiple tests that are both time consuming and costly. OBJECTIVE: To determine the feasibility of ECS to directly detect the amebic parasites in vivo. DESIGN: Prospective, single-center, pilot study. SETTING: Tertiary-care university hospital. PATIENTS: This study involved 5 patients who were suspected to have amebic colitis by conventional colonoscopy in our institute. INTERVENTIONS: A super-magnifying ECS with 450 x magnification. MAIN OUTCOME MEASUREMENTS: We compared ECS findings with those of conventional methods-serum antibody tests and histology of colon biopsy specimens. RESULTS: We successfully visualized the amebic trophozoites in all 5 cases. In contrast, 3 specimens had positive results on serology, and 3 had positive histology results on hematoxylin and eosin staining. LIMITATIONS: Pilot study with a limited number of patients. Findings were compared only with serology and histology findings. CONCLUSIONS: ECS would be a useful tool for the prompt diagnosis of amebic colitis via the real-time in vivo visualization of amebic trophozoites. PMID- 20579648 TI - Cap-fitted colonoscopy: a randomized, tandem colonoscopy study of adenoma miss rates. AB - BACKGROUND: Failures of adenoma detection diminish the effectiveness of colonoscopy. OBJECTIVE: This study investigated the impact of cap-fitted colonoscopy (CFC) on the adenoma miss rate at colonoscopy. DESIGN: Randomized, tandem colonoscopy study. SETTING: University hospital. PATIENTS: This study involved patients undergoing elective screening or surveillance colonoscopy. INTERVENTION: Patients were randomized to undergo cap-fitted (n = 52) or regular, high-definition (n = 48) colonoscopy before undergoing a second colonoscopy by the alternate method. During CFC, a plastic cap or hood was attached to the tip of the colonoscope, which was used to flatten haustral folds and improve mucosal exposure. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was the miss rate for adenomas between patients who underwent CFC first and patients who underwent regular colonoscopy first. RESULTS: A total of 238 adenomas were detected in 67 patients (67%), with a combined overall miss rate of 27.7%, comprising 66 missed adenomas in 38 patients. Patients undergoing initial CFC had a significantly lower miss rate for all adenomas compared with that of patients undergoing regular colonoscopy (21% vs 33%, P = .039). Miss rates with CFC were significantly lower for adenomas of <=5 mm (22% vs 35%; P = .037). There was no significant difference in per-patient miss rates between the initial CFC group (51%, n = 18) and the initial regular colonoscopy group (63%, n = 20, P = .36). LIMITATIONS: Single-center study with two endoscopists. CONCLUSION: CFC reduces miss rates for all adenomas and specifically for small adenomas. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00577083). PMID- 20579649 TI - Large-diameter therapeutic channel duodenoscope to facilitate simultaneous deployment of side-by-side self-expandable metal stents in hilar cholangiocarcinoma. AB - BACKGROUND: Hilar cholangiocarcinoma (CC) is unresectable in 80% to 90% of cases. Placement of side-by-side bilateral self-expandable metal stents (SEMSs) can be technically challenging in these patients because deployment of the first stent can preclude passage of the second stent. METHODS: Using a prototype large diameter therapeutic channel (6-mm) duodenoscope, we positioned guidewires into the right and left intrahepatic systems. Two predeployed uncovered SEMSs with 7.5F delivery systems were passed side by side over each guidewire and deployed simultaneously. DESIGN: Observational clinical feasibility study. SETTING: Tertiary referral center. RESULTS: This technique was attempted in 6 patients with malignant hilar biliary obstruction. Successful placement was achieved in all, with significant improvement in symptoms and cholestasis. LIMITATIONS: Small number of patients. CONCLUSION: This simple technique using a prototype large diameter therapeutic channel duodenoscope facilitates placement of bilateral side by-side hilar SEMSs. PMID- 20579650 TI - Anatomic-manometric correlation of the upper esophageal sphincter: a concurrent US and manometry study. AB - BACKGROUND: The pharyngoesophageal segment commonly referred to as the upper esophageal sphincter (UES) generates a high-pressure zone (HPZ) between the pharynx and the esophagus. However, the exact anatomical components of the UES HPZ remain incompletely determined. OBJECTIVE: To systematically define the US signature of various components of the pharyngoesophageal junction and to determine how these structures contribute to the development of the UES-HPZ. DESIGN: Prospective, experimental study. SETTING: Tertiary Academic Medical Center. PATIENTS: This study involved 18 healthy volunteers. INTERVENTION: We studied 5 participants by using a high-frequency US miniprobe (US-MP) and concurrent fluoroscopy and another 13 participants by using the US-MP and concurrent manometry. MAIN OUTCOME MEASUREMENTS: Relative contribution of various muscles in the UES-HPZ. RESULTS: Manometrically, the UES-HPZ had a median length of 4.0 cm (range 3.0-4.5 cm). A C-shaped muscle, believed to represent the cricopharyngeus muscle, was observed for a median length of 3.5 cm (range 2.0-4.0 cm). The oval configuration representing the esophageal contribution to the UES was seen in 10 of 13 participants (77%) at the distal HPZ (esophagus to UES transition zone). The flat configuration of the inferior constrictor muscle was noted in 7 of 13 participants (54%) at the proximal HPZ (UES to pharynx transition zone). There were 4 to 5 wall layers versus 3 layers in the distal and proximal HPZ, respectively. The mean (+/- SD) muscle thickness was relatively constant along the length of the UES-HPZ. LIMITATIONS: Air artifacts in the UES HPZ. CONCLUSION: The configuration and layers of the UES-HPZ vary along its length. The upper esophagus is a significant contributor to the distal UES-HPZ. PMID- 20579651 TI - Braided cerclage wires: a biomechanical study. AB - BACKGROUND: One of the drawbacks that makes many surgeons reluctant to use cerclage wires is the risk of periosteal vascular compromise. A new, easily applied braided wire configuration has been developed to improve mechanical wire gripping and to decrease the contact area between the hardware and the bony surface. MATERIALS AND METHODS: Braided wires with two diameters (1 mm and 1.5 mm) were compared to single strand and double-strand wire configurations. The biomechanical properties, peak and elongation loads,and wire pressure imprint points of this new configuration were evaluated in the current study. RESULTS: The braided wire was found to have the same peak load as the double-strand wire (P = 0.315) and more than twice the peak load than the single-strand wire (P = 0.0001), but a much shorter elongation peak than the other two. The imprint test showed that the braided wire has an interrupted dotted pattern compared to the continuous circular one that characterises the single-strand and double strand wires, indicating less potential damage to the bone. CONCLUSIONS: The braided cerclage wire may decrease the extent of insult to the bone by decreasing the contact area between the hardware and the bony surface and by enhancing stability by reducing the elongation peak, affording increased fracture fixation stability. PMID- 20579653 TI - Dextran-grafted cation exchanger based on superporous agarose gel: adsorption isotherms, uptake kinetics and dynamic protein adsorption performance. AB - A novel chromatographic medium for high-capacity protein adsorption was fabricated by grafting dextran (40kDa) onto the pore surfaces of superporous agarose (SA) beads. The bead was denoted as D-SA. D-SA, SA and homogeneous agarose (HA) beads were modified with sulfopropyl (SP) group to prepare cation exchangers, and the adsorption and uptake of lysozyme on all three cation exchange chromatographic beads (SP-HA, SP-SA and SP-D-SA) were investigated at salt concentrations of 6-50mmol/L. Static adsorption experiments showed that the adsorption capacity of SP-D-SA (2.24mmol/g) was 78% higher than that of SP-SA (1.26mmol/g) and 54% higher than that of SP-HA (1.45mmol/g) at a salt concentration of 6mmol/L. Moreover, salt concentration had less influence on the adsorption capacity and dissociation constant of SP-D-SA than it did on SP-HA, suggesting that dextran-grafted superporous bead is a more potent architecture for chromatographic beads. In the dynamic uptake of lysozyme to the three cation exchange beads, the D(e)/D(0) (the ratio of effective pore diffusivity to free solution diffusivity) values of 1.6-2.0 were obtained in SA-D-SA, indicating that effective pore diffusivities of SP-D-SA were about two times higher than free solution diffusivity for lysozyme. At 6mmol/L NaCl, the D(e) value in SA-D-SA (22.0x10(-11)m(2)/s) was 14.4-fold greater than that in SP-HA. Due to the superior uptake kinetics in SA-D-SA, the highest dynamic binding capacity (DBC) and adsorption efficiency (the ratio of DBC to static adsorption capacity) was likewise found in SP-D-SA. It is thus confirmed that SP-D-SA has combined the advantages of superporous matrix structure and drafted ligand chemistry in mass transport and offers a new opportunity for the development of high-performance protein chromatography. PMID- 20579652 TI - The aorta wall of patients presenting to the emergency department with acute myocardial infarction by cardiac magnetic resonance. AB - BACKGROUND: Inflammation has been shown to be a major component in the pathophysiology of acute coronary syndrome (ACS). In patients presenting with acute myocardial infarction (AMI), a critical component of the ACS spectrum, multiple coronary arteries are involved during this inflammatory process. In addition to the coronary vasculature, the inflammatory cascade has also been shown to affect the carotid arteries and possibly the aorta. PURPOSE: To assess the involvement of the aorta during AMI by cardiac magnetic resonance (CMR). METHODS: We prospectively evaluated the aortic wall by CMR in 123 patients. 78 patients were enrolled from the emergency department (ED), who presented with chest pain and were classified as either: (1) AMI: elevated troponin levels and typical chest pain or (2) non-cardiac chest pain (CP): negative troponins and a normal stress test or normal cardiac catheterization. We compared these 2 groups to a group of 45 asymptomatic diabetic patients. The descending thoracic aortic wall area (AWA) and maximal aortic wall thickness (AWT) were measured using a double inversion recovery T-2 weighted, ECG-gated, spin echo sequence by CMR. RESULTS: Patients with AMI were older, more likely to smoke, had a higher incidence of claudication, and had higher CRP levels. The AWA and maximal AWT were greater in patients who presented to the ED with ACS (2.11+/-0.17 mm(2), and 3.17+/-0.19 mm, respectively) than both patients presenting with non-cardiac CP (1.52+/-0.58 mm(2), p<0.001; and 2.57+/-0.10 mm, p<0.001) and the diabetic patients (1.38+/-0.58 mm(2), p<0.001; and 2.30+/-0.131 mm, p<0.001). The difference in the aortic wall characteristics remained significant after correcting for body mass index, hyperlipidemia, statins and C-reactive protein. There was no difference in maximal AWT or AWA between patients with non-cardiac CP and patients with diabetes. CONCLUSION: Patients with AMI have a significantly greater maximal aortic wall thickness and area compared to patients with non cardiac CP. Longitudinal studies are needed to assess whether this increase is due to inflammation or a higher atherosclerotic burden. PMID- 20579654 TI - "Click" immobilized perphenylcarbamated and permethylated cyclodextrin stationary phases for chiral high-performance liquid chromatography application. AB - Two cyclodextrin-based chiral stationary phases have been prepared by immobilization of functionalized mono-6-azido-beta-CD derivatives to alkynyl modified silica via "click" chemistry and applied to the HPLC enantioseparation of various chiral compounds. The perphenylcarbamated CD CSP (CCP-CSP) exhibited excellent chiral recognition of a wide range of analytes including racemic aryl alcohols, flavonoids, bendroflumethiazide, atropine and some beta-blockers. Methanol proved to be a better organic modifier than acetonitrile for most of the analytes with the exception of bendroflumethiazide. The "click" chemistry immobilized permethylated CD CSP (CCM-CSP) afforded poor chiral recognition for most analytes, but could resolve non-aromatic ionone derivatives which were not separated on CCP-CSP. These results suggest that resolution with cyclodextrin derived CSPs depend on a complex interplay of 'host'-'guest' inclusion, hydrogen bonding, pi-pi and hydrophobic interactions. PMID- 20579655 TI - Mass transfer resistance in narrow-bore columns packed with 1.7 microm particles in very high pressure liquid chromatography. AB - Surprisingly, the mass transfer kinetic properties of columns packed with superficially porous particles are markedly different from those of columns packed with fully porous particles. The performances of 2.1mmx150mm columns packed with a new type of sub-2microm particles, the superficially porous 1.7microm Kinetex-C(18), and with the classical 1.7microm BEH-C(18) fully porous particles were measured and are discussed. The sample was naphtho[2,3-a]pyrene; the use of different mobile phase compositions allowed a comparison between data measured with retention factors of k(') approximately 2 and k(') approximately 20. The minimum reduced height equivalent to a theoretical plate (HETP) of the two columns were similar, at h(min)=2.0. However, this minimum HETP was observed at a markedly shorter reduced linear velocity for the column packed with totally porous particles, between 5 and 7 for BEH, than for the one packed with shell particles, between 8 and 10 for Kinetex. This result is explained by the combination of (1) a 35% smaller B term for the Kinetex column than for the BEH column, due to the 37% lower porous volume of the former; (2) a larger reduced A term for the Kinetex column (1.6), showing a relatively poorly packed column with significant trans-column velocity biases than for the BEH column (ca. 1.0); and (3) a much lesser dependance of the efficiency on the mobile phase velocity at high velocities for the Kinetex than for the BEH column, when these columns are placed in the oven of the instrument under still-air conditions. The heat friction affects significantly more the efficiency of the BEH column than that of the Kinetex column. This unexpected result is accounted for by the three times smaller heat conductivity of the BEH bed (lambda(BEH) approximately 0.25 W/m/K) than that of the Kinetex bed (lambda(Kinetex) approximately 0.75W/m/K). PMID- 20579656 TI - Characterization of the wettability of thin nanostructured films in the presence of evaporation. AB - Vapor chambers using conventional porous membrane wicks offer limited heat transfer rates for a given thickness. This limitation can be addressed through wick nanostructuring, which promises high capillary pressures and precise control of the local porosity. This work develops a measurement technique for the wettability of nanostructured wicks based on optical imaging. Feasibility is demonstrated on a hydrophilic silicon nanowire array (SiNW) synthesized using the Vapor-Liquid-Solid (VLS) growth mechanism followed by surface plasma treatment. The wettability is determined by comparing the time-dependent liquid interface rise with a model that accounts for capillary, viscous, and gravitational forces and for evaporation. This model is demonstrated to be useful in extracting internal contact angle from thin ( approximately 10microm) porous films. PMID- 20579657 TI - Controlling surface porosity and release from hydrogels using a colloidal particle coating. AB - Recent studies suggest that coating microcapsules by a shell composed of impenetrable colloidal particles (thereby forming 'colloidosomes') can be used to control surface porosity, and therefore, permeability. The voids between the particles in the coating define the size of the surface pores available for transport. However, to date, data demonstrating this selectivity has been largely qualitative. In this paper we examine, quantitatively, the effect of a surface coating (shell), composed of colloidal particles, on release from hydrogels. We find that the presence of a colloidal shell does indeed reduce the rate of transport of three model molecules: Aspirin, caffeine, and FITC-dextran with MW of approximately 3000-5000. Contrary to expectation, however, we find that for all three molecules the reduction in transport rate is largely independent of the dimensions of the particles composing the shell, despite differences that range over three orders of magnitude. In the case of the small molecules, caffeine and aspirin, the colloidal shell reduces the effective diffusion coefficient by a factor of 3. In the case of dextran, the suppression in the release rate due to the colloidal shell was much larger. These results are explained using a simple diffusion model that accounts for the volume fraction and diameter of the colloidal particles in the shell, and the size of the diffusing molecules. PMID- 20579658 TI - Protein interactions with bottle-brush polymer layers: Effect of side chain and charge density ratio probed by QCM-D and AFM. AB - Silica surfaces were coated with a range of cationic bottle-brush polymers with 45 units long poly(ethylene oxide) side chains, and their efficiency in reducing protein adsorption was probed by QCM-D, reflectometry and AFM. Preadsorbed layers formed by bottle-brush polymers with different side chain to charge ratio was exposed to two proteins with different net charge, lysozyme and BSA. The reduction in protein adsorption was found to depend on both the type of protein and on the nature of the polyelectrolyte layer. The most pronounced reduction in protein adsorption was achieved when the fraction of charged backbone segments was in the range 0.25-0.5 equivalent to a fraction of poly(ethylene oxide) side chains of 0.75-0.5. It was concluded that these polymers have enough electrostatic attachment points to ensure a strong binding to the surface, and at the same time a sufficient amount of poly(ethylene oxide) side chains to counteract protein adsorption. In contrast, a layer formed by a highly charged polyelectrolyte without side chains was unable to resists protein adsorption. On such a layer the adsorption of negatively charged BSA was strongly enhanced, and positively charged lysozyme adsorbed to a similar extent as to bare silica. AFM colloidal probe force measurement between silica surfaces with preadsorbed layers of bottle-brush polymers were conducted before and after exposure to BSA and lysozyme to gain insight into how proteins were incorporated in the bottle-brush polymer layers. PMID- 20579659 TI - Adhesion of Ferroplasma acidiphilum onto pyrite calculated from the extended DLVO theory using the van Oss-Good-Chaudhury approach. AB - The adhesion behavior of Ferroplasma acidiphilum archaeon to pyrite mineral was investigated experimentally and theoretically. F. acidiphilum showed high affinity to adhere to pyrite surface at acidic regions, however low affinity was observed at neutral and alkaline regions. The microbe-mineral adhesion was assessed by the extended DLVO theory. Hamaker constants, electron donors, electron acceptors and surface charges for the microbe and the mineral were experimentally determined. The extended DLVO theory was used to explain the adhesion results. Significant changes to the pyrite surface properties after being treated with the microbial cells were observed. Pyrite lost its hydrophobic nature and became hydrophilic, the contact angle of untreated pyrite was 61 degrees and this decreased to 36 degrees after the treatment. As a consequence, the flotation experiment results showed that F. acidiphilum strain could act as a good depressant for pyrite in xanthat flotation; where in absence of F. acidiphilum cells, over 95% of pyrite can be recovered as a float. However, when the mineral was pretreated with F. acidiphilum cells, less than 20% can be recovered as a float. PMID- 20579660 TI - Narrative abilities in monolingual and dual language learning children with specific language impairment. AB - PURPOSE: The aim of this study was to compare narrative abilities in children with specific language impairment (SLI) who are monolingual and those who are dual language learners. METHOD: The participants were 26 children with SLI, 14 monolingual English speakers and 12 dual language learners. The dual language learners were English dominant and spoke a variety of other languages in the home. The two SLI groups were compared using standardized tests and measures from two narrative samples. RESULTS: Compared to the monolingual children, the dual language learners achieved lower scores on standardized tests of morphosyntax but not on measures of language form derived from the narrative samples. Both groups achieved below average scores on productivity, narrative structure, literate language, and language form measures from the narrative samples. CONCLUSION: The data suggest that narrative samples can be a sensitive way to assess the language skills of dual language learners with specific language impairment. Furthermore, the findings are consistent with the position that English standardized tests may be a biased assessment measure when used with dual language learners, particularly for the assessment of expressive morphosyntactic skills. LEARNING OUTCOMES: Readers will be able to (1) describe the narrative abilities of typically developing dual language learners; (2) describe similarities between the narrative abilities of children with SLI who are monolingual and dual language learners; (3) identify ways to analyses narratives at a variety of levels. PMID- 20579661 TI - Seven-month-olds detect ordinal numerical relationships within temporal sequences. AB - Previous evidence has shown that 11-month-olds represent ordinal relations between purely numerical values, whereas younger infants require a confluence of numerical and non-numerical cues. In this study, we show that when multiple featural cues (i.e., color and shape) are provided, 7-month-olds detect reversals in the ordinal direction of numerical sequences relying solely on number when non numerical quantitative cues are controlled. These results provide evidence for the influence of featural information and multiple cue integration on infants' proneness to detect ordinal numerical information. PMID- 20579662 TI - Serotonergic function, substance craving, and psychopathology in detoxified alcohol-addicted males undergoing tryptophan depletion. AB - Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the ll genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males. PMID- 20579663 TI - High dose cyclophosphamide treatment in Marburg variant multiple sclerosis A case report. AB - Marburg variant multiple sclerosis (MS) is an acute, fulminant and monophasic variant of MS that usually leads to death within weeks to months. No consistently successful treatment is known. We describe a 26-year-old woman who developed acute and progressive motor and sensory deficits. Demyelinating disease was suspected based on brain and spinal MRI and cerebrospinal fluid results. Multiple treatments including corticosteroids, plasma exchange and intravenous immunoglobulin could not halt her clinical and radiological deterioration. She became near quadriplegic and developed motor aphasia. A diagnosis of Marburg variant MS was considered and she was given high dose cyclophosphamide (HiCy) at 50mg/kg/day for four consecutive days, followed by granulocyte colony-stimulating factor six days after the completion of the cyclophosphamide treatment. HiCy successfully induced neutropenia. She started to show a steady neurological improvement from day 17 of HiCy treatment. MR studies two months after HiCy treatment showed significant decrease in the size and enhancement of the lesions. Five months later she had minimal residual right-sided weakness and was able to ambulate without assistance. The great outcome seen in our case suggests that HiCy should be considered as a potential treatment for patients with Marburg variant MS who fail to respond to standard therapy. PMID- 20579664 TI - Tracheal torsion assessed by a computer-generated 3-dimensional image analysis predicts tracheal self-expandable metallic stent fracture. AB - OBJECTIVE: Self-expandable metallic stents are used to relieve airway stenosis in selected patients; however, fracture of these stents may occur. This analysis aims to investigate the extent of tracheal torsion, assessed by a computed generated reformatted 3-dimensional tracheal reconstruction from 2-dimensional computed tomographic images in predicting fracture of tracheal self-expandable metallic stents. METHODS: From 2001 to 2007, 32 patients (aged 62.8 +/- 14.1 years) with benign tracheal diseases received chest computed tomographic evaluation and Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents. The bending angles of the central axis and peripheral wall of the trachea at choke point were measured from the computed-generated 3 dimensional tracheal images. RESULTS: Seventeen fractured stents were found among the patients. The median time for stent fracture was 865 days after implantation. Receiver operating characteristic curve analysis revealed that a 19 degrees bending angle of the tracheal central axis (area under the curve, 0.929; 95% confidence interval, 0.847-1.012; P < .001) and a 44 degrees maximal bending angle of the peripheral tracheal wall (area under the curve, 0.918; 95% confidence interval, 0.821-1.012; P < .001) had maximal power in predicting tracheal fracture of self-expandable metallic stents. CONCLUSIONS: Three dimensional tracheal reconstructions from 2-dimensional chest computed tomographic data are useful in assessing the severity of tracheal torsion. Tortuous trachea with a central axis bending angle of 19 degrees or more and peripheral tracheal wall maximal bending angle of 44 degrees or more were associated with a high probability of fracture of the self-expandable metallic stent. PMID- 20579666 TI - Altered right ventricular papillary muscle position and orientation in patients with a dilated left ventricle. AB - OBJECTIVE: To investigate the impact of left ventricular dilatation on right ventricular papillary muscle displacement. METHODS: Thirteen patients underwent high-resolution cardiac magnetic resonance imaging at Emory University Hospital: Seven patients with congestive heart failure and a dilated left ventricle composed the dilated left ventricular group, and 6 normal subjects were used as a control. A total of 120 cardiac magnetic resonance imaging slices were acquired in a short-axis view at end diastole for each subject. Cardiac magnetic resonance imaging slices were used to identify the papillary muscle tip position in 3 dimensional coordinates for the septal, posterior, and anterior papillary muscles. The centroid of the papillary muscle coordinates was used as the reference point for comparison between subjects. The relative orientation between the right ventricular papillary muscles was evaluated and compared between the dilated left ventricular group and normal subjects. RESULTS: Dilatation of the left ventricle resulted in a significant (P = .05) displacement of the septal right ventricular papillary muscle toward the centroid: normal group, 0.0285 +/- 0.036 mm/mm versus dilated left ventricular group, 0.1437 +/- 0.026 mm/mm. More specifically, the septal papillary muscle significantly (P = .03) moved away from the septal wall (normal group: 0.61 +/- 0.09 mm/mm, dilated left ventricular group: 0.379 +/- 0.037 mm/mm). Specific locations of all 3 right ventricular papillary muscles were reported for normal subjects and patients with a dilated left ventricle. CONCLUSIONS: Patients with a dilated left ventricle have significantly increased displacement of the septal right ventricular papillary muscle away from the septum when compared with normal controls. This demonstrates pathophysiologic contribution of the left ventricle to specific papillary muscle alterations within the right ventricle. PMID- 20579667 TI - Mitral ring annuloplasty relieves tension of the secondary but not primary chordae tendineae in the anterior mitral leaflet. AB - OBJECTIVE: Mitral ring annuloplasty is routinely applied as an adjunct procedure in reconstructive surgery on the mitral valve leaflets or chordae tendineae. It is assumed that mitral ring annuloplasty relieves tensile stress on the repaired valve tissue and thereby improves the durability of the procedure, but the indication is disputable. We sought to study the effect of mitral ring annuloplasty on the tension of the primary and secondary chordae tendineae of the anterior mitral valve leaflet in vivo. METHODS: In 17 adult pigs miniature chordal force transducers were sutured to the 2 major fixing primary chordae and the 2 strut secondary chordae of the anterior leaflet. Baseline measurements were accomplished. After randomization, one group (n = 10) underwent a mitral ring annuloplasty (Carpentier-Edwards Classic, 28 mm; Edwards Lifesciences, Irvine, Calif), and the second group (n = 7) served as controls and underwent a sham operation. Simultaneous recordings of chordae tendineae tension and hemodynamics and echocardiographic assessment of anterior leaflet occlusion area were acquired at baseline and after the mitral ring annuloplasty/sham operation. RESULTS: Mitral ring annuloplasty caused a significant reduction of the anterior leaflet occlusion area (1.85 +/- 0.16 vs 4.63 +/- 0.37 cm(2)) and the tension of the secondary chordae (0.33 +/- 0.06 vs 0.67 +/- 0.12 N) but did not affect the tension of the primary chordae (0.24 +/- 0.07 vs 0.17 +/- 0.06 N). The sham procedure had no effect on these variables. CONCLUSIONS: In normal porcine hearts mitral ring annuloplasty primarily relieves stress on the anterior leaflet belly rather than the leading edge. Mitral ring annuloplasty might therefore protect repairs of the central portion of the anterior leaflet and secondary chordae but not repairs that solely involve the anterior leaflet's leading edge and adjacent chordae. PMID- 20579668 TI - Early outcomes of deliberate nonoperative management for blunt thoracic aortic injury in trauma. AB - OBJECTIVE: Traumatic blunt aortic injury has traditionally been viewed as a surgical emergency, whereas nonoperative therapy has been reserved for nonsurgical candidates. This study reviews our experience with deliberate, nonoperative management for blunt thoracic aortic injury. METHODS: A retrospective chart review with selective longitudinal follow-up was conducted for patients with blunt aortic injury. Surveillance imaging with computed tomography angiography was performed. Nonoperative patients were then reviewed and analyzed for survival, evolution of aortic injury, and treatment failures. RESULTS: During the study period, 53 patients with an average age of 45 years (range, 18-80 years) were identified, with 28% presenting to the Stanford University School of Medicine emergency department and 72% transferred from outside hospitals. Of the 53 patients, 29 underwent planned, nonoperative management. Of the 29 nonoperative patients, in-hospital survival was 93% with no aortic deaths in the remaining patients. Survival was 97% at a median of 1.8 years (range, 0.9-7.2 years). One patient failed nonoperative management and underwent open repair. Serial imaging was performed in all patients (average = 107 days; median, 31 days), with 21 patients having stable aortic injuries without progression and 5 patients having resolved aortic injuries. CONCLUSIONS: This experience suggests that deliberate, nonoperative management of carefully selected patients with traumatic blunt aortic injury may be a reasonable alternative in the polytrauma patient; however, serial imaging and long-term follow-up are necessary. PMID- 20579669 TI - Noninvasive cerebral oxygenation may predict outcome in patients undergoing aortic arch surgery. AB - OBJECTIVES: Surgical repair of the aortic arch remains technically challenging and is associated with considerable morbidity and mortality. Cerebral oximetry is a noninvasive technology that can monitor the regional oxygen saturation of the frontal cortex. We hypothesized that magnitude and duration of decreased intraoperative regional oxygen saturation was associated with postoperative organ dysfunction. Additionally, we sought to identify regional oxygen saturation threshold values that are predictive of organ dysfunction. METHODS: The intraoperative regional oxygen saturation values of 30 patients undergoing aortic arch surgery were recorded and analyzed. Postoperative complications were categorized as "major" and "minor." Severe adverse outcome, extubation time, intensive care unit length of stay, and hospital length of stay data were collected and compared with the integrals of regional oxygen saturation and time (area under the threshold) spent beneath predetermined absolute threshold limits. RESULTS: Twenty subjects underwent hemiarch replacement, and 10 subjects received total aortic arch replacements. There were 30 major and 29 minor complications identified. Sixteen (53.3%) patients had at least 1 major complication. Logistic regression showed statistically significant associations between area under the threshold and severe adverse outcome incidence for regional oxygen saturation thresholds of 60% (P = .038) and 65% (P = .025). Patients who spent more than 30 minutes under the absolute threshold of 60% had an extended hospital stay of 4 days leading to an additional cost of $8300.00. CONCLUSIONS: Our findings lend evidence to support the association of decreased perioperative cerebral oxygenation values with poor outcomes after aortic arch surgery. PMID- 20579671 TI - Re: Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society: T. Neveus, P. Eggert, J. Evans, A. Macedo, S. Rittig, S. Tekgul, J. Vande Walle, C. K. Yeung and L. Robson J Urol 2010; 183: 441-447. PMID- 20579672 TI - Re: The commonly performed nerve sparing total prostatectomy does not acknowledge the actual nerve courses: K. D. Sievert, J. Hennenlotter, I. A. Laible, B. Amend, U. Nagele and A. Stenzl J Urol 2009; 181: 1076-1081. PMID- 20579674 TI - Germination and establishment of the invasive cordgrass Spartina densiflora in acidic and metal polluted sediments of the Tinto River. AB - Heavy metal pollution is common in rivers in the vicinity of mining areas. In these polluted environments, the survival of alien species with a high tolerance to metals may be favored. The Tinto River (Southwest Iberian Peninsula) is an excellent natural laboratory for the study of plants' responses to acidic and metal polluted sediments. This work analyzes the tolerance of the alien species Spartina densiflora to low pH and high metal loads in the Tinto River. The main aim of this study was to determine if this alien species can invade landward along the banks of the Tinto River. S. densiflora seeds were able to germinate in heavy metal polluted aerobic sediments even at pH 2. However, these conditions decreased S. densiflora final germination, altered germination dynamics, decreased aerial and subterranean growth rates, and prevented its establishment. PMID- 20579675 TI - Are marine plastic particles transport vectors for organic pollutants to the Arctic? AB - Plastic litter accounts for 50-80% of waste items stranded on beaches, floating on the ocean surface and lodged in the seabed. Organic pollutants can be absorbed onto plastic particles from sea water, attached to their surfaces or included in the plastic matrix as additives. Such chemicals may be transported to remote regions by buoyant plastics and ocean currents. We have estimated mass fluxes of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and perfluorooctanoic acid (PFOA) to the Arctic via the main ocean currents and compared them to those in the dissolved state and in air. Substance fluxes with atmospheric or sea water currents account for several tons per year, whereas those mediated by plastics are four to six orders of magnitude smaller. However, the significance of various pollutant transport routes does not depend only on absolute mass fluxes but also on bioaccumulation in marine food chains. PMID- 20579676 TI - [Transient ischemic attack: the end justifies the means]. PMID- 20579677 TI - Lipid status, paraoxonase-1 activity and metabolic parameters in serum of heifers and lactating cows related to oxidative stress. AB - The objective of this study was to investigate serum lipids, metabolic parameters and activity of the anti-oxidative enzyme paraoxonase-1 (PON1). The study was conducted on non-pregnant heifers with optimal health status and on healthy dairy cows in the period of intensive lactation, assuming that the energy and metabolic demands during lactation reduce anti-oxidative protection. Total cholesterol and HDL-cholesterol concentrations were significantly higher (P<0.05) in lactating cows than in heifers. Bilirubin concentration and gamma-glutamyltransferase (GGT) activity were also significantly higher in lactating cows (P<0.05), indicating increased hepatic efforts of cows to meet energy requirements for lactation. Significantly lower PON1 activity and PON1/HDL ratio in lactating cows compared to heifers (P<0.05) showed that metabolic efforts during pregnancy, parturition and lactation influence PON1 activity due to oxidative stress. Concurrent increase in total and HDL-cholesterol during lactation indicated that the HDL particle is a major carrier of cholesterol in cows. PMID- 20579678 TI - Teratogenic and cytogenetic effects of ivermectin and its interaction with P glycoprotein inhibitor. AB - Experiments in animals proved that P-glycoprotein (Pgp) forms a functional barrier between maternal and fetal blood circulation in the placenta, thus protecting the fetus from exposure to xenobiotics during pregnancy. In this study we aimed to demonstrate the effects of administration of ivermectin (anthelmentic drug, Pgp substrates), either alone or simultaneously with verapamil (Pgp inhibitor) in Wister rats on fetal development, maternal bone marrow for detection of micronuclei (MN), chromosomal aberrations and mitotic index (MI) and embryonic liver cells for cellular proliferation indicated by MI, and bleeding from umbilical vessels for detection of embryonic micronuclei (MN). The results revealed that administration of ivermectin or verapamil at 6th through 15th day of gestation did not significantly altered fetal development. While, co administration of ivermectin and verapamil clearly disturbed fetal development as indicated from abnormal feto-maternal attachment and a significant decrease in fetal weights and numbers. Furthermore, co-administration of both drugs induced a significant increase in resorption sites, post-implantation loss and external, visceral and skeletal abnormalities. They also induced genotoxicity in both dam and embryonic cells indicated by reduced mitotic index, increased number of micronucleated erythrocytes in both, and increased different types of chromosomal aberrations in dam cells, while ivermectin alone show some genotoxic effect on somatic cells of dams and the embryos. Verapamil induced reduction of embryonic mitotic index. We concluded combined treatment of ivermectin and verapamil severely affect fetal genetic material and development and induced genotoxic effect in somatic cells of the dams. PMID- 20579679 TI - Management of an outbreak of brucellosis due to B. melitensis in dairy cattle in Spain. AB - Brucella melitensis is a major human and animal pathogen, with a wide host range that includes all domestic ruminant species, although small ruminants are its preferred hosts. Outbreaks in cattle due to B. melitensis have become a worldwide emerging problem particularly difficult to control due to the lack of knowledge on the epidemiology in this host species and of an effective vaccine. However, combination of molecular tools and strict biosecurity measures can help to solve these difficulties and eventually eradicate the disease from infected herds. In the present report, management of an outbreak in Spain involving four farms, more than 2000 cattle and several human cases is described. Application of Multiple Locus VNTR Analysis (MLVA) allowed identifying the most likely source of infection. Stamping out and test-and-slaughter strategies were applied, proving their usefulness to control the outbreak depending on infection level, and without the need of other alternative measures. PMID- 20579681 TI - Removal of arsenic from contaminated groundwater by solar-driven membrane distillation using three different commercial membranes. AB - Investigations on solar-driven membrane distillation (SDMD) were carried out for removal of arsenic from contaminated groundwater. Three different types of hydrophobic membranes made of polytetrafluoroethylene (PTFE) and polypropylene (PP) with surface area of 120 * 10(-4)m(2) were used as flat sheet in a direct contact membrane distillation (DCMD) set up in a cross flow module. Effects of initial arsenic concentration in the feed, feed velocity, feed temperature and distillate inlet temperature on arsenic removal efficiency and flux were studied where temperatures of feed and distillate were found to have significant effect on the flux. Almost 100% arsenic separation was achieved without wetting membrane pore even after 120 h of operation. The PTFE membrane with a flux of 49.80 kg/m(2)h was found to the best one out of the tested membranes. The study shows that solar-driven DCMD can effectively separate arsenic from groundwater using a cross flow membrane module with PTFE hydrophobic membrane. PMID- 20579680 TI - Induction of monocyte chemoattractant protein-1 by nicotine in pancreatic ductal adenocarcinoma cells: role of osteopontin. AB - BACKGROUND: Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein (MCP)-1 and evaluated the role of OPN in mediating these effects. METHODS: MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3-300 nmol/L) or OPN (0.15-15 nmol/L) were analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Luciferase labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry. RESULTS: Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P < .05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60% of invasive PDA lesions, of whom 66% were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA. CONCLUSION: Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation by inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects. PMID- 20579682 TI - A theoretical study of a direct contact membrane distillation system coupled to a salt-gradient solar pond for terminal lakes reclamation. AB - Terminal lakes are water bodies that are located in closed watersheds with the only output of water occurring through evaporation or infiltration. The majority of these lakes, which are commonly located in the desert and influenced by human activities, are increasing in salinity. Treatment options are limited, due to energy costs, and many of these lakes provide an excellent opportunity to test solar-powered desalination systems. This paper theoretically investigates utilization of direct contact membrane distillation (DCMD) coupled to a salt gradient solar pond (SGSP) for sustainable freshwater production at terminal lakes. A model for heat and mass transport in the DCMD module and a thermal model for an SGSP were developed and coupled to evaluate the feasibility of freshwater production. The construction of an SGSP outside and inside of a terminal lake was studied. As results showed that freshwater flows are on the same order of magnitude as evaporation, these systems will only be successful if the SGSP is constructed inside the terminal lake so that there is little or no net increase in surface area. For the study site of this investigation, water production on the order of 2.7 x 10(-3) m(3) d(-1) per m(2) of SGSP is possible. The major advantages of this system are that renewable thermal energy is used so that little electrical energy is required, the coupled system requires low maintenance, and the terminal lake provides a source of salts to create the stratification in the SGSP. PMID- 20579683 TI - Ecotoxicological assessment of surfactants in the aquatic environment: combined toxicity of docusate sodium with chlorinated pollutants. AB - The toxicity of perfluorinated surfactants perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorobutane sulfonate (PFBS) and PF-656 as well as the sulfosuccinate surfactant docusate sodium has been examined using two bioluminescence inhibition assays based on the marine bacterium Vibrio fischeri and the self-luminescent cyanobacterial recombinant strain Anabaena CPB4337. We also determined multigenerational toxicity towards the growth of the algae Pseudokirchneriella subcapitata. With EC(50) values in the 43-75 mg/L range, docusate sodium exhibited a higher toxicity towards the three organisms than PFOS, PFOA, PF-656 and PFBS. We investigated the toxicological interactions of the most toxic surfactant, docusate sodium, with two chlorinated compounds, triclosan and 2,4,6-trichlorophenol (TCP), in their binary and ternary mixtures using the method of the combination index based on the median-effect equation. In general, the binary mixture of the chlorinated compounds triclosan and TCP exhibited antagonism, which was stronger for the growth test using P. subcapitata. Except for the green alga, the binary mixtures of docusate sodium with TCP or triclosan showed synergism at medium to high effect levels; the synergistic behaviour predominating in the ternary mixture and in the three tested species. This result highlights the potential toxicological risk associated with the co-occurrence of this surfactant with other pollutants. PMID- 20579684 TI - Flame retardants and organochlorine pollutants in bald eagle plasma from the Great Lakes region. AB - We report measurements of polybrominated diphenyl ethers and of emerging flame retardants in the plasma of nestling bald eagles sampled from early May to late June of 2005. Concentrations of total PBDEs ranged from 0.35 ng g(-1) ww to 29.3 ng g(-1) ww (average=5.7+/-1.9 ng g(-1) ww). The most abundant congeners were BDE 47, BDE-99, and BDE-100. The fully brominated congener, BDE-209, was detected in approximately one third of the samples at an average concentration of 1.2+/-0.72 ng g(-1) ww. Several emerging flame retardants, such as pentabromoethylbenzene (PBEB), hexabromocyclododecanes (HBCDs), and Dechlorane Plus (DP), were detected in these samples. Polychlorinated biphenyls (PCBs) and organochlorine pesticides were also detected at levels close to those previously published. A statistically significant relationship was found between total PBDE concentrations and total PCB and p,p'-DDE concentrations, suggesting that these compounds share a common source, which is most likely the eagle's food. PMID- 20579685 TI - Runoff pollutants of a highly trafficked urban road--correlation analysis and seasonal influences. AB - The quality of road runoff at a highly trafficked road has been studied for 2 years. 63 storm events have been sampled and analyzed. Besides pH value and electric conductivity the concentrations of zinc (Zn), copper (Cu), lead (Pb), nickel (Ni) and cadmium (Cd), both in dissolved and particulate form, de-icing salt, total and dissolved organic carbon (TOC and DOC), suspended solids (SS) have been monitored. Correlation analysis showed a significant relationship between the total metal concentrations with TOC and SS. A considerable seasonal increase in pollutant concentrations has been observed for Cu, TOC, SS, pH value and especially for Zn during the cold season. The mean values during winter time were multiple times higher than measured during the warm season. In contrast, the fractionation of heavy metals was not affected by seasonal variations, but remarkable fluctuations were observed between different rain events with dissolved fractions above 90%. As a result of this and due to the high pollutant load on fine particles, best management practices (BMPs) only implementing sedimentation are not recommended for treatment of heavily polluted urban road runoff. From the data obtained it can be concluded, that the de-icing salt has only a weak influence for higher pollutant concentrations. The increase of heavy metal concentrations occurs because of increased tear and wear due to application of gravel at cold weather conditions. No significant influence of the length of antecedent dry weather periods could be observed most likely due to street sweeping, winds and air turbulences caused by traffic. PMID- 20579686 TI - Bioavailability of organochlorine compounds in aqueous suspensions of fullerene: evaluated with medaka (Oryzias latipes) and negligible depletion solid-phase microextraction. AB - The wide application of engineered nanomaterials, such as fullerene (C(60)), will inevitably lead to their release into the aqueous environment, which may alter the bioavailability of organic compounds to aquatic organisms. Negligible depletion solid-phase microextraction (nd-SPME) together with medaka (Oryzias latipes) bioaccumulation were used to study the effects of aqueous suspensions of fullerene (nC(60)) on the bioavailability of eight organochlorine compounds (OCCs) (logK(OW) 3.76-6.96). Freely dissolved concentrations of OCCs decreased by 11.5-88.4% at addition of 5mgL(-1)nC(60) as indicated by reduced equilibrium concentrations in the SPME fiber coating, the highest reduction being observed for the most hydrophobic OCCs. Medaka bioaccumulation study demonstrated that at the kinetic uptake regime, nC(60) significantly decreased the bioaccumulation of the high hydrophobic OCCs (logK(OW)>6), but slightly enhanced the bioaccumulation of the less hydrophobic OCCs (logK(OW)<6). The OCC concentrations in medaka (C(fish)) at the kinetic uptake regime linearly correlated with that in nd-SPME fiber (C(fiber)) without nC(60) (p=0.007-0.013, R(2)=0.666-0.723), but this correlation deteriorated with the presence of nC(60) (p=0.073-0.081, R(2)=0.423 0.440). These results suggest that in nC(60) the uptake mechanism of OCCs to medaka is different from that to nd-SPME fiber. While only the freely dissolved OCCs are available to nd-SPME fiber, both the freely dissolved and the nC(60) associated OCCs contributed to the accumulation of OCCs to medaka. PMID- 20579687 TI - The use of Sunpatiens (Impatiens spp.) as a bioindicator of some simulated air pollutants--using an ornamental plant as bioindicator. AB - Sunpatiens were exposed separately or combined to ozone gas (130 ppb), fluoranthene (10 microM) and sulphuric acid mists (pH 3) sprayed as simulated pollutants in chamber conditions for 21 d. The treatments negatively affected the gas (CO(2) and moisture) exchange, leaf chlorophyll fluorescence, and the leaf quality expressed in chlorophyll value (SPAD). Fluoranthene and the acid individual negative effects on the measured eco-physiological variables were nearly the same on Sunpatiens; their effects became aggravated on combining the duo. The foliar symptom assessments of chlorosis, necrosis and stippling revealed severe damages in ozone containing treatments compared with other treatments. The presence of fluoranthene exuberate ozone negative effects on some of the plant eco-physiological status. Where mannitol (1mM) additions were contained in treatments, mitigation effects of the negative impact of pollutants resulted. These findings indicated that Sunpatiens can be used as an active bioindicator of singular and multiple pollutants in field conditions. PMID- 20579688 TI - Joint effects of three plant protection products to the terrestrial isopod Porcellionides pruinosus and the collembolan Folsomia candida. AB - The effects of simultaneous application of plant protection products are of concern since the uses of different products pose an additional risk to non target soil organisms. The effects of binary combinations of dimethoate, glyphosate and spirodiclofen, an insecticide an herbicide and an acaricide, on the avoidance behaviour of the terrestrial isopod Porcellionides pruinosus and the reproductive effort of Folsomia candida were assessed using the two reference models of concentration addition (CA) and independent action (IA). Results of single exposure to the three pesticides indicated a clear dose related avoidance response of the isopods in the highest concentrations tested of the three as well as a strong decrease in collembolan adult survival and concomitant number of juveniles produced. In the combined experiments, antagonism was found in 7 out of the 12 combinations, four combinations followed the reference models, and only in one combination synergism was detected (lower doses of glyphosate and spirodiclofen applied to P. pruinosus). In conclusion, it seems that mixing and applying these products, at the recommended field application rate, does not lead to enhanced toxicity, hence limited risk is associated with the joint application of these pesticides. PMID- 20579689 TI - Biotic and abiotic degradation of four cephalosporin antibiotics in a lake surface water and sediment. AB - Cephalosporins are widely used veterinary and human antibiotics, but their environmental fate and impacts are still unclear. We studied degradation of four cephalosporins (cefradine, cefuroxime, ceftriaxone, and cefepime) from each generation in the surface water and sediment of Lake Xuanwu, China. The four cephalosporins degraded abiotically in the surface water in the dark with half lives of 2.7-18.7d, which were almost the same as that in sterilized surface water. Under exposure to simulated sunlight, the half-lives of the cephalosporins decreased significantly to 2.2-5.0d, with the maximal decrease for ceftriaxone from 18.7d in the dark to 4.1d under the light exposure. Effects of dissolved organic matter (DOM) and nitrate on photodegradation of the cephalosporins were compound-specific. While DOM (5 mg L(-1)) stimulated the photodegradation of only cefradine (by 9%) and cefepime (by 34%), nitrate (10 microM) had effects only on cefepime (stimulation by 13%). Elimination rates of the cephalosporins in oxic sediment (half-lives of 0.8-3.1d) were higher than in anoxic sediment (half-lives of 1.1-4.1d), mainly attributed to biodegradation. The data indicate that abiotic hydrolysis (for cefradine, cefuroxime, and cefepime) and direct photolysis (for ceftriaxone) were the primary processes for elimination of the cephalosporins in the surface water of the lake, whereas biodegradation was responsible for the elimination of the cephalosporins in the sediment. Further studies are needed on chemical structure, toxicity, and persistence of transformation products of the cephalosporins in the environment. PMID- 20579690 TI - Sorption of endocrine disrupting chemicals by condensed organic matter in soils and sediments. AB - Sorption of 17alpha-ethinyl estradiol (EE2) and bisphenol A (BPA) by nonhydrolyzable carbon (NHC), black carbon (BC), and bulk soils and sediments was examined. All sorption isotherms were nonlinear and fitted both Freundlich and Dubinin-Ashtakhov (DA) models. The single-point organic carbon (OC)-normalized distribution coefficient (K(OC)) of EE2 for the isolated NHC and BC was 2.7-4.8 times and 5.4-12.9 times greater, respectively, than that of the bulk samples. However, no clear trend in BPA K(OC) values was observed. Based on the contribution of soil/sediment organic matter (SOM) fractions to the overall sorption of BPA or EE2 by the bulk samples, condensed SOM (NHC and BC) generally played a dominant role to the overall sorption. The BPA adsorption capacity (Q(OC)(0)) from the DA model was higher than that of EE2 on NHC and there was obvious difference in isotherm nonlinearity (n) between EE2 and BPA. These results suggest that BPA may have more access to the pore sites of NHC samples than EE2. The pi-pi bonds formed between BPA and NHC or BC may be stronger than that between EE2 and NHC or BC. This would be attributed to the fact that BPA has two benzene rings, and can also be used to explain the difference in hexadecane water partition coefficient (K(HW))-normalized K(OC) values (K(OC)/K(HW)) of BPA and EE2 after factoring out the hydrophobic effect. These findings could be useful for predicting fate and ecological risks of endocrine disrupting chemicals (EDCs) (e.g., EE2 and BPA) in natural environments especially when soils or sediments become receptors for EDCs. PMID- 20579691 TI - Degradation of yew, ragwort and rhododendron toxins during composting. AB - Recent concerns have been raised that plants such as ragwort (Senecio jacobaea), yew (Taxus baccata) and rhododendron (Rhododendron ponticum) that are toxic to livestock may be included in compost windrows but may not be fully detoxified by the composting process. This study investigates the decomposition during composting of toxic pyrrolizidine alkaloids present in ragwort, taxines (A and B) present in yew, and grayanotoxins (GTX I, II, and III) present in rhododendron during composting. Plant samples were contained within microporous bags either towards the edge or within the centre of a pilot-scale compost heap. They were destructively harvested at regular intervals over 1200 degrees C cumulative temperature (about three months). Samples were analysed for levels of toxins by liquid chromatography time of flight mass spectrometry (LC-TOF-MS). Pyrrolizidine alkaloids and taxines were shown to degrade completely during the composting process. While GTX I showed significant reductions, concentrations of GTX III remained unchanged after 1200 degrees C cumulative temperature. However, estimates of exposure to grazing livestock coming into contact with source segregated green waste compost containing up to 7% rhododendron suggest that GTX III poses no appreciable risk. PMID- 20579692 TI - Quantification of fossil organic matter in contaminated sediments from an industrial watershed: validation of the quantitative multimolecular approach by radiocarbon analysis. AB - The quantitative multimolecular approach (QMA) based on an exhaustive identification and quantification of molecules from the extractable organic matter (EOM) has been recently developed in order to investigate organic contamination in sediments by a more complete method than the restrictive quantification of target contaminants. Such an approach allows (i) the comparison between natural and anthropogenic inputs, (ii) between modern and fossil organic matter and (iii) the differentiation between several anthropogenic sources. However QMA is based on the quantification of molecules recovered by organic solvent and then analyzed by gas chromatography-mass spectrometry, which represent a small fraction of sedimentary organic matter (SOM). In order to extend the conclusions of QMA to SOM, radiocarbon analyses have been performed on organic extracts and decarbonated sediments. This analysis allows (i) the differentiation between modern biomass (contemporary (14)C) and fossil organic matter ((14)C-free) and (ii) the calculation of the modern carbon percentage (PMC). At the confluence between Fensch and Moselle Rivers, a catchment highly contaminated by both industrial activities and urbanization, PMC values in decarbonated sediments are well correlated with the percentage of natural molecular markers determined by QMA. It highlights that, for this type of contamination by fossil organic matter inputs, the conclusions of QMA can be scaled up to SOM. QMA is an efficient environmental diagnostic tool that leads to a more realistic quantification of fossil organic matter in sediments. PMID- 20579693 TI - Enhanced thrombin formation and fibrinolysis during acute Puumala hantavirus infection. AB - INTRODUCTION: Nephropathia epidemica (NE) is a viral hemorrhagic fever with renal syndrome associated with thrombocytopenia and mild bleeding. We assessed activation of coagulation and fibrinolysis during the acute phase of NE. MATERIALS AND METHODS: 19 hospital-treated patients were involved. Plasma levels of D-dimer, prothrombin fragments 1+2 (F1+2), activated partial thromboplastin time (APTT), prothrombin time (PT%), thrombin time (TT), fibrinogen, antithrombin (AT), protein S free antigen (PS), protein C (PC) and complete blood count (CBC) were measured three times during the acute phase and once at 32-54 days after the onset of fever (recovery phase). Laboratory abnormalities were evaluated by the disseminated intravascular coagulation (DIC) scoring advocated by the International Society of Thrombosis and Haemostasis (ISTH). RESULTS: APTT was prolonged and D-dimer and F1+2 increased during the acute phase of NE. AT, PC and PS decreased, and TT was shortened, all implying increased thrombin generation. Acutely F1+2 was 3.4-fold and D-dimer even 24-fold higher compared with the recovery phase (median 726 vs 213 pmol/l, and median 4.8 vs 0.2mg/l, respectively, p<0.001 for both). Platelet count correlated with AT, PC, and PS (r=0.73, r=0.81, and r=0.71, respectively, p<0.001 for all) as well as with fibrinogen (r=0.72, p<0.001). Only five patients fulfilled the ISTH diagnosis of DIC. CONCLUSIONS: During acute NE thrombocytopenia was associated with decreased natural anticoagulants, shortened thrombin time and enhanced fibrinolysis. Augmented thrombin formation and fibrinolysis characterize this hantavirus infection. PMID- 20579694 TI - Experimental unilateral spermatic cord torsion: the effect of polypolymerase enzyme inhibitor on histopathological and biochemical changes in the early and late periods in the ipsilateral and contralateral testicles. AB - OBJECTIVES: We wanted to show early and late biochemical, histopathological, and apoptotic changes caused by unilateral spermatic cord torsion in ipsilateral and contralateral testicles and the effect of the poly (adenosine triphosphate ribose) polymerase (PARP) inhibitor, nicotinamide, on these changes in early and late periods. MATERIALS AND METHODS: Forty-seven Wistar albino rats were divided into 2 major groups as early and late periods. Subsequently, each group was divided into subgroups as control, sham, torsion-detorsion (TD), TD treated with saline (TDS), and TD treated with nicotinamide (TDN). Left testicles were subjected to spermatic cord torsion for 4 hours. Thirty-minutes before detorsion, 0.2 mL saline or 10 mg/kg nicotinamide was administered intraperitoneally to the TDS and TDN groups, respectively. Bilateral orchidectomy was performed by the end of the fourth hour in early and 2 months after TD in late groups and the animals were sacrificed. Apoptosis, Johnsen Tubular Biopsy Score, and seminiferous tubule diameter (STD) were used to evaluate histopathological changes. Ischemia reperfusion injury-related changes were assessed by levels of malondialdehyde (MDA) and total and free glutathione in serum. RESULTS: There were no significant differences between groups in terms of serum MDA and total and free glutathione levels. Rats given nicotinamide had a higher number of spermatogonia in seminiferous tubules in early and late periods when compared with the untreated group (P <.05). In early and late groups, mean STD of contralateral and ipsilateral testicles were higher in rats given nicotinamide when compared with untreated groups. No significance was observed in terms of STD between early and late groups. Late groups treated with nicotinamide had less apoptosis when compared with untreated groups (P <.05). CONCLUSIONS: Nicotinamide may successfully decrease ischemia-reperfusion injury in early and late periods in both testicles. PMID- 20579695 TI - A comparative study of clinical value of single B-mode ultrasound guidance and B mode combined with color doppler ultrasound guidance in mini-invasive percutaneous nephrolithotomy to decrease hemorrhagic complications. AB - OBJECTIVES: To compare the clinical value of single B-mode ultrasonography and B mode combined with color Doppler ultrasonography in the guidance of mini-invasive percutaneous nephrolithotomy (m-PCNL) to decrease the incidence of hemorrhagic complications. METHODS: A total of 297 patients with renal stones who had undergone m-PCNL were retrospectively categorized into 2 groups. Group 1 (187 patients) underwent m-PCNL with single B-mode ultrasound guidance and group 2 (110 patients) underwent m-PCNL with combined B-mode and color Doppler ultrasound guidance. The clinical characteristics of the patients, intraoperative and postoperative characteristics, complications, especially hemorrhagic complications, and blood transfusion rate were recorded and compared. RESULTS: No statistically significant differences in age, height, weight, stone burden, operative time, stone-free rate, or length of postoperative hospital stay were found between the 2 groups. In group 2, a statistically significant decrease in the transfusion rate was found compared with group 1 (P <.05). In group 1, 5 patients (2.6%) required a blood transfusion, 2 (1.1%) developed a renal arteriovenous fistula and required embolotherapy, 2 (1.1%) developed hemorrhage and required embolotherapy after surgery, 16 (8.6%) developed capillary hemorrhage during surgery but had no hemorrhage postoperatively. However, no serious hemorrhagic complications were found in group 2. Only 3 patients (2.7%) developed capillary hemorrhage during surgery, and no hemorrhage occurred postoperatively. CONCLUSIONS: Using combined B-mode and color Doppler ultrasound guidance during in m-PCNL resulted in the real-time detection and avoidance of the renal blood vessels during puncture and decreased the incidence of hemorrhagic complications, especially in the patients with a solitary and compensative kidney. PMID- 20579696 TI - Bilateral ureteric quadruplication with renal calculus. AB - Ureteric quadruplication is an extremely rare congenital anomaly. We present radiologic images of a young woman with a renal calculus with bilateral ureteric quadruplication. She presented with right flank pain, and the intravenous urogram revealed a calculus in the superior calyx that drained into the upper most moiety of a partially quadruplicated ureter. PMID- 20579697 TI - Posterior rhabdosphincter reconstruction during robot-assisted radical prostatectomy: critical analysis of techniques and outcomes. AB - Many centers have recently implemented posterior rhabdosphincter reconstruction (PRR) into robot-assisted radical prostatectomy (RARP) with the objective of earlier continence recovery. We comprehensively review the anatomic and functional changes occurring post prostatectomy along with the reconstructive techniques and published outcomes of PRR. Several case control studies show a better continence rate within the first 3 months, whereas the only randomized control trial presents a conflicting conclusion. Unfortunately, all reported studies lack uniform surgical technique, continence definition, and measures, making comparison difficult. Although initial results appear favorable, the true continence benefit of PRR remains debatable and requires further research. PMID- 20579698 TI - Comprehensive quality-of-life outcomes in the setting of a multidisciplinary, equal access prostate cancer clinic. AB - OBJECTIVES: To identify racial and demographic factors that influence treatment choice and its resulting impact on health-related quality of life (HRQoL) for prostate cancer patients. METHODS: Patients presenting to an equal access, military, multidisciplinary prostate cancer clinic composed the study group. The Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short Form 36 were the instruments used. Evaluation was performed before treatment and every 3 months after treatment. RESULTS: The study group comprised 665 patients. Caucasians were 3-fold more likely to choose surgery (radical prostatectomy [RP]) over external beam radiation therapy (EBRT). Patients who earned more than $100,000 annually disproportionately chose RP (P < .0001). Similarly, those having a graduate school degree disproportionally chose RP (P < .0001). Patients undergoing RP had the greatest risk of urinary function decline (P < .0001) and sexual bother (P = .0003). African Americans (AA) had a greater risk of urinary function decline irrespective of treatment choice. Patients undergoing EBRT had equivalent urinary function to expectant management (EM) at 12 months (P < .0001). Brachytherapy was the only treatment that posed an increased risk of urinary bother decline when compared with EM (P = .0217). EBRT alone did not show significant decrement in sexual function when compared with EM. CONCLUSIONS: RP was chosen by patients of Caucasian ethnicity and patients with higher income and education level, despite providing the greatest risk of HRQoL decline. EBRT had no significant impact on urinary function, sexual function, or sexual bother scores at 12 months. EBRT may be offered to older patients with minimal HRQoL impact. Pretreatment counseling of HRQoL outcomes is essential to overall prostate cancer management. PMID- 20579699 TI - Prognostic significance of undetectable ultrasensitive prostate-specific antigen nadir after radical prostatectomy. AB - OBJECTIVES: To investigate the prognostic significance of undetectable ultrasensitive prostate-specific antigen (PSA) nadir in patients who received radical prostatectomy (RP) for prostate cancer. METHODS: We reviewed records of 384 patients who received RP for prostate cancer and were followed for at least 2 years with ultrasensitive PSA testing. Undetectable ultrasensitive PSA level was defined as <0.001 ng/mL. Subjects were categorized according to PSA nadirs: <0.001 ng/mL (group 1), 0.001 ng/mL <= and < 0.02 ng/mL (group 2), 0.02 ng/mL <= and < 0.05 ng/mL (group 3), or >=0.05 ng/mL (group 4). Multivariate analysis was performed to identify independent predictors of biochemical recurrence-free survival. A receiver operator characteristics (ROC) curve was used to assess performances of multivariate model in predicting biochemical recurrence. RESULTS: Overall, 206 (53.6%) patients showed undetectable ultrasensitive PSA nadir. Subjects of groups 1, 2, 3, and 4 demonstrated significant differences in biochemical recurrence-free survivals (log rank P <.001). In multivariate analysis, undetectable ultrasensitive PSA nadir (P <.001) was observed to be an independent predictor of biochemical recurrence-free survival along with preoperative PSA level (P = .030), pathologic stage (P = .014), and pathologic Gleason score (P = .042). Area under the ROC curve demonstrating predictive performances of the multivariate model, which included ultrasensitive PSA nadir, was significantly larger than that of the model without it (P <.001). CONCLUSIONS: Our results demonstrated that undetectable ultrasensitive PSA nadir is a useful predictor of biochemical recurrence-free survival among contemporary patients who received RP for prostate cancer. PMID- 20579700 TI - Lower urinary tract dysfunction and ultrasound assessment of bladder wall thickness in children with cerebral palsy. AB - OBJECTIVES: To evaluate lower urinary tract dysfunction (LUTD) based on questionnaire symptom scoring and ultrasound assessment of bladder wall thickness (BWT) in children with cerebral palsy (CP). METHODS: A total of 97 children with CP were enrolled in the study. The patients were either symptomatic or asymptomatic with respect to lower urinary tract symptoms. All children underwent a urinary questionnaire and renal ultrasonography. Ultrasound assessment of BWT was completed in 72 cases. RESULTS: A total of 47 patients were female and 50 were male. The mean age was 8 years 8 months (SD 3 years 1 month), with a range of 5-18 years. Urinary incontinence was present in 43 patients (44.3%). Based on the questionnaire, LUTD was found in 59 patients (60.8%). The mean BWT was 2.30 mm. There was no statistically significant difference between continent and incontinent children (2.46 vs 2.19 mm) or between children with and without LUTD (2.43 vs 2.12 mm). CONCLUSIONS: LUTD is common in children with CP and occurred in 60.8% of the patients assessed. BWT did not correlate with the presence of bladder dysfunction or incontinence. Ultrasound assessment of BWT was not relevant for diagnosis of lower urinary tract dysfunction. PMID- 20579701 TI - Preliminary study of diagnostic utility of molecular beacons in bladder cancer. AB - OBJECTIVES: To investigate the feasibility of molecular beacons (MBs) for screening urine samples from patients with suspected bladder cancer. Our previous study showed that MBs could detect bladder cancer cells and cells shed in the urine from patients with bladder cancer. METHODS: Samples from 35 patients with bladder cancer and 35 healthy adults were initially evaluated. Cyanine 3-labeled MBs linked to a survivin mRNA probe were used to detect exfoliative cells in urine. Exfoliative cytology, enzyme-linked immunosorbent assay, and Western blotting of the tissues were used to confirm the MB results. We then evaluated the urine samples from 187 patients with suspected bladder cancer. All 187 patients also underwent cystoscopy. RESULTS: In the initial cohort evaluated, MBs detected cancerous cells in 28 (80%) of the 35 patients with confirmed bladder cancer. Survivin protein was detected by Western blotting in 25 (71.4%) of the 35 patients. The sensitivity and specificity of enzyme-linked immunosorbent assay was 54.3% (20 of 35) and 68.6% (24 of 35), respectively. In a large group of patients with suspected bladder cancer, the sensitivity of MBs was 77.3% (85 of 110) and the specificity was 76.6% (59 of 77) compared with the cystoscopy data. Differences in the protein levels between the tumor grades and stages were not significant. CONCLUSIONS: Our results have demonstrated that it is feasible to detect survivin mRNA in the exfoliated cells in urine using MBs. With further development, MBs could be used in a noninvasive clinical diagnostic procedure for the early detection of bladder cancer and postoperative follow-up. PMID- 20579702 TI - Cross-sectional study examining four types of male penile and urethral "play". AB - OBJECTIVES: To provide further quantitative and qualitative evidence about men who insert foreign liquids and objects into their penis and/or urethra. METHODS: As part of a larger, cross-sectional study examining men (n = 445) with genital piercings (GP), 2 questions inquired whether the respondents had penile tattoos and/or inserted other materials, such as fluids and foreign objects, into their penis and urethra. RESULTS: Four different practices have been described in the literature: embedding (a) foreign objects and/or (b) liquids subcutaneously into penile tissue, as well as inserting (c) liquids and/or (d) foreign objects into the urethra. In our study, 354 (78%) men with GP responded to the 2 questions; 85 (24%) replied affirmatively and 68 (80%) provided comments. Respondents coined their practices penile and/or urethral "play." Two respondents embedded metal balls into their penis, 1 at age 13 injected water for penis enlargement; 11 inserted liquids into the urethra, and 63 reported insertion of 32 different objects, frequently urethral sounds or "sounding" (n = 33/52%) were mentioned. Major motivation themes focused on sexual stimulation and experimentation. Penile tattoos (n = 14) were also reported, mainly for esthetics. Few complications or STDs were reported. CONCLUSIONS: Basic demographic assumptions of those who participate in these actions were challenged, and this study provides evidence of a wider distribution of men using penile or urethral play, and "sounding." Clinician awareness of these practices are important to obtain accurate health histories, manage genitourinary tract complications, as well as provide applicable patient education. PMID- 20579703 TI - Prevalence of erectile dysfunction in living donors before and after nephrectomy in China. AB - OBJECTIVES: To investigate the prevalence of erectile dysfunction (ED) in living donors before and after nephrectomy in China. METHODS: From January 2006 to December 2008, erectile function of 94 living donors was evaluated before and after nephrectomy by International Index of Erectile Function, version 5 (IIEF 5). A subanalysis was performed by splitting the total cohort into 2 age groups: those <40 years of age (group 1, n = 21) and those >or=40 years of age (group 2, n = 73). RESULTS: Before and after nephrectomy, the prevalence of ED in group 1 was 9.5% and 19.0% respectively, and in group 2 was 38.4% and 56.2%. The difference between groups was statistically significant at the stage of preoperation (9.5% vs 38.4%, P = .012) and 12 months postoperation (19.0% vs 56.2% P = .003). Compared with the stage of preoperation, the prevalence of ED at the stage of postoperation was significantly increased at group 2 (38.4% vs 56.2%, P = .031), but not in group 1 (9.5% vs 19.0%, P = .663). CONCLUSIONS: The prevalence of ED increased in living donors aged more than 40 years after nephrectomy in China. The change in sexual function of these living donors after nephrectomy should cause clinicians' attention. PMID- 20579704 TI - Xanthogranulomatous pyelonephritis in an adolescent. AB - Xanthogranulomatous pyelonephritis is a chronic, inflammatory disease of the kidney rarely found in the pediatric population. We report the case of a 16-year old boy with fever, microscopic hematuria, and an enlarging cystic renal mass on ultrasonography. The patient had no evidence of renal stones and no known risk factors, other than a recent tattoo performed with unsterile equipment. Because the differential diagnoses included Wilms tumor, he underwent open exploration and nephrectomy. The histopathologic findings were consistent with xanthogranulomatous pyelonephritis, and cultures grew methicillin-resistant Staphylococcus aureus. The etiology was believed to be bacterial seeding from the unsterile tattoo. PMID- 20579705 TI - Oncologic results of laparoscopic renal cryoablation for clinical T1a tumors: 8 years of experience in a single institution. AB - OBJECTIVES: To review the oncologic outcomes of laparoscopic renal cryoablation (LRC) for small renal masses (SRMs) <4 cm. METHODS: The present study was an observational, retrospective analysis of LRC in 123 patients. The indications for LRC were solid SRMs of the kidney <4 cm in diameter diagnosed on preoperative computed tomography or magnetic resonance imaging as an enhancing mass. Follow-up was determined using magnetic resonance imaging. Local recurrence after LRC was defined as an enlarging or persistently enhancing treatment site on follow-up imaging. RESULTS: A total of 131 SRMs in 123 patients (91 men and 32 women) were treated from September 2000 to June 2008. The mean tumor size was 2.14 +/- 0.86 cm (range 0.5-4). Biopsy cores from the 123 patients revealed clear cell renal cell carcinoma (RCC) in 69 patients (56.1%), papillary RCC in 8 (6.53%), chromophobe RCC in 3 (2.4%), mucinous, tubular, and spindle RCC in 1 (0.8%), oncocytoma in 27 (21.9%), angiomyolipoma in 5 (4.1%), and xanthogranulomatous pyelonephritis in 1 patient (0.8%). The biopsy findings were nondiagnostic (fibrotic/necrotic tissue) in 9 cases (7.3%). The mean follow-up was 46.04 +/- 25.75 months (median 41, range 12-96). In 44 patients with RCC and a mean follow up of 61.3 +/- 13.76 months, the cancer-specific survival rate was 100% and the overall survival rate was 93.2%. None of the 53 patients (RCC plus those with nonmalignant lesions) who had follow-up >5 years developed radiographic recurrence. CONCLUSIONS: Our findings have confirmed that LRC can be considered a safe and intermediate-term effective method to treat SRMs. PMID- 20579706 TI - Anteroposterior dissection HoLEP: a modification to prevent transient stress urinary incontinence. AB - OBJECTIVES: The prevalence of transient stress urinary incontinence (SUI) after HoLEP has been reported to be as high as 44%. Anteroposterior dissection HoLEP was newly developed to protect the urethral sphincter and therefore lower the incidence rate of SUI. This study was conducted to determine the SUI incidence rate after anteroposterior dissection HoLEP. METHODS: Sixty-eight consecutive patients with benign prostatic hyperplasia underwent HoLEP from January to December 2008. The first 31 cases (Surgery 1) underwent HoLEP according to Gilling's method. The next 37 cases (Surgery 2) underwent anteroposterior dissection HoLEP, where adenoma was dissected antegradely. This antegrade movement of the cystoscope allows the apical gland to be removed from the sphincter without causing damage. Surgical quality indexes (hemoglobin change, operating time, resected prostate volume) between the 2 groups were compared. All patients were assessed at 2 weeks postoperatively for clinical SUI, international prostate symptom score (IPSS), quality of life (QoL), and peak flow rates (Q(max)). RESULTS: Patient characteristics and surgical quality indexes did not differ between the 2 groups. Clinical SUI was found in 25.2% of cases in the Surgery 1 group, but only 2.7% in the Surgery 2 group. IPSS, QoL and Q(max.) were significantly improved postoperatively in both groups. At 2 weeks, the QoL of the Surgery 2 group was significantly improved compared with that observed for Surgery 1 (1.5 +/- 1.1 vs 2.4 +/- 1.0, P = .02). The Q(max.) of Surgery 2 was significantly higher compared with Surgery 1 (19.8 +/- 8.4 vs 13.0 +/- 4.7 ml/s, P = .02). CONCLUSIONS: These results indicate that our anteroposterior dissection HoLEP is a promising procedure to avoid postoperative SUI and also to substantially improve QoL. PMID- 20579707 TI - Fatal outcome caused by intravenous infusion of bacille Calmette-Guerin. PMID- 20579708 TI - A multicenter, double-blind, placebo-controlled trial to assess the efficacy of sildenafil citrate in men with unrecognized erectile dysfunction. AB - OBJECTIVE: Erectile dysfunction (ED) may be present but unrecognized in men with other comorbidities, such as cardiovascular disease (CVD), diabetes, or lower urinary tract symptoms (LUTS). The efficacy of sildenafil citrate treatment for ED in men who did not self-identify with or were unsure about whether they had ED, but had ED based on International Index of Erectile Function Erectile Function domain (IIEF-EF) scores, was evaluated. METHODS: Men with an ED associated comorbidity were asked, "Do you have ED?" Those who answered "no" or "unsure" and were diagnosed with ED (score of or=30 kg/m(2)), and waist circumference >or=40 inches were the most frequently reported risk factors. Sildenafil-treated men had improved scores on both functional and psychosocial measures. Most adverse events were mild to moderate. CONCLUSIONS: Many men do not recognize that they have ED; sildenafil treatment improved sexual function and satisfaction in these men. Because ED affects quality of life, it should be suspected and assessed in men with risk factors for ED. PMID- 20579709 TI - Prognostic value of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer receiving adjuvant intravesical mitomycin C therapy. AB - OBJECTIVES: To analyze the prognostic values of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer who were treated with adjuvant intravesical mitomycin C. METHODS: From 2001 to 2006, 129 patients with nonmuscle-invasive bladder cancer who had undergone transurethral resection and adjuvant intravesical mitomycin C therapy. Patients with primary, single, Stage TaG1 lesions and those with T1G3 or carcinoma in situ lesions were excluded. The expression of p53 and Ki-67 was measured by immunohistochemistry on tissue sections after transurethral resection. The clinical and pathologic data were collected in a prospectively maintained bladder cancer database program. RESULTS: The mean follow-up period was 48.6 months (range 6.1-96.0). Of the 129 patients, 61 (47.3%) developed recurrence and 15 (11.6%) developed progression to muscle-invasive disease. The expression of p53 was not associated with the patient outcomes, but Ki-67 overexpression was related to progression-free survival on univariate analysis (relative risk 4.38, 95% confidence interval 1.48 13.01, P = .006). On multivariate analysis, Ki-67 overexpression was significantly associated with progression-free survival (relative risk 3.40, 95% confidence interval 1.04-11.05, P = .042). In the patients with Ki-67 overexpression, the 1- and 5-year progression-free survival rate was 98.0% and 73.9%, respectively. When the combination of p53 and Ki-67 expression was assessed in the multivariate model, the simultaneous overexpression of p53 and Ki 67 did not predict for progression-free survival (adjusted relative risk 1.16; 95% confidence interval 0.21-6.20, P = .863). CONCLUSIONS: These results suggest that Ki-67 expression can identify a subset of intermediate-risk patients with nonmuscle-invasive bladder cancer in whom intravesical mitomycin C therapy could be effective. PMID- 20579710 TI - Bochdalek hernia with obstructive uropathy. AB - Bochdalek hernias are postero-medial diaphragmatic defects that usually contain peritoneal fat and often remain asymptomatic. We present a unique case in which involvement of the adjacent ureter in the hernia defect resulted in obstructive uropathy. PMID- 20579711 TI - Large renal metastasis from rare pulmonary neoplasm. AB - A 50-year-old man, with a history of right lower lobectomy for pulmonary adenocystic carcinoma, presented with chronic flank pain due to a large mass in the right kidney. He also had bilateral pulmonary nodules and cardiac masses, indicating metastatic disease. Simultaneous metastatic involvement of the kidney and the heart from a rare pulmonary tumor made this case unique in the prevailing medical data. PMID- 20579712 TI - Single-port risk-reducing salpingo-oophorectomy with and without hysterectomy: surgical outcomes and learning curve analysis. AB - OBJECTIVE: Based on considerable prospective data, risk-reducing salpingo oophorectomy (RRSO) is one of the most beneficial interventions available to reduce ovarian/breast cancer risk in BRCA carriers and high-risk women. The purpose of this study was to describe the initial surgical outcomes and learning curve analysis associated with laparoendoscopic single-site (LESS) RRSO with and without hysterectomy. METHODS: A retrospective, multi-institutional analysis of BRCA carriers and women at high risk for breast/ovarian cancer who underwent LESS RRSO with and without hysterectomy in 2009 was performed. Data collected included age, BMI, procedure, operative time, length of hospital stay, postoperative pain scores, and post operative complications. Student t-test, Pearson correlation coefficient, and multivariate linear regression were used for analysis. RESULTS: A total of 58 patients were evaluated; 36 (63%) were BRCA1/2 carriers and 38 (63%) had breast cancer. Patients' mean age and BMI were 46 years and 27 kg/m(2), respectively. Most patients were Caucasian (76%), and at the time of prophylactic surgery, 53% of patients were undergoing active breast cancer treatment. Mean operative time was 38.1 minutes (16-80 minutes). All cases were performed successfully via the LESS approach, and there were no surgical complications. Multivariate linear regression analysis was done, and after controlling for study site, previous abdominal surgery, active cancer treatment, and BMI, operative time was only influence by number of cases performed, p=0.019. CONCLUSIONS: LESS RRSO is feasible and safe with favorable surgical and cosmetic outcomes. In our experience, surgical proficiency is possible after 10-15 cases. The LESS approach may be ideal for BRCA mutation carriers and breast cancer patients because of a short convalescence, permitting minimal interruption in any ongoing cancer treatment and the potential psychological benefits from improved cosmesis and pain control. Prospective studies are needed to assess the relative benefits of LESS compared with more conventional minimally invasive approaches. PMID- 20579713 TI - Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma. AB - BACKGROUND: Airflow in the lungs of patients with allergic asthma is impaired by excessive mucus production and airway smooth muscle contractions. Elevated levels of the cytokines IL-4 and IL-13 are associated with this pathology. In vitro studies have suggested that IL-4 receptor alpha (IL-4Ralpha) signaling on smooth muscle cells is critical for airway inflammation and airway hyperresponsiveness. OBJECTIVE: To define the contribution of IL-4 and IL-13 to the onset of asthmatic pathology, the role of their key receptor IL-4Ralpha in smooth muscle cells was examined in vivo. METHODS: By using transgenic smooth muscle myosin heavy chain(cre)IL-4Ralpha(-/lox) mice deficient in IL-4Ralpha in smooth muscle cells, in vivo effects of impaired IL-4Ralpha signaling in smooth muscle cells on the outcome of asthmatic disease were investigated for the first time. Allergic asthma was introduced in mice by repeated sensitization with ovalbumin/aluminum hydroxide on days 0, 7, and 14, followed by intranasal allergen challenge on days 21 to 23. Mice were investigated for the presence of airway hyperresponsiveness, airway inflammation, allergen-specific antibody production, T(h)2-type cytokine responses, and lung pathology. RESULTS: Airway hyperresponsiveness, airway inflammation, mucus production, T(h)2 cytokine production, and specific antibody responses were unaffected in smooth muscle myosin heavy chain(cre)IL-4Ralpha( /lox) mice compared with control animals. CONCLUSION: The impairment of IL 4Ralpha on smooth muscle cells had no effect on major etiologic markers of allergic asthma. These findings suggest that IL-4Ralpha responsiveness in airway smooth muscle cells during the early phase of allergic asthma is not, as suggested, necessary for the outcome of the disease. PMID- 20579714 TI - Biological agents: new drugs, old problems. PMID- 20579716 TI - Gene-environment interactions influence airways function in laboratory animal workers. AB - BACKGROUND: Most diseases, including asthma, result from the interaction between environmental exposures and genetic variants. Functional variants of CD14 negatively affect lung function in farm workers and children exposed to animal allergens and endotoxin. OBJECTIVE: We hypothesized that CD14 polymorphisms interact with inhaled endotoxin, mouse allergen, or both to decrease airways function in laboratory animal workers. METHODS: Three hundred sixty-nine Caucasian workers completed a symptom and work exposure questionnaire, skin prick testing, and spirometry. Individual exposure estimates for endotoxin and murine allergen were calculated by weighting task-based breathing zone concentrations by time reported for each task and length of time in the current job. Real-time PCR was used to assess CD14/-1619, -550, and -159 alleles. Multiple linear regression predicting airways function included an interaction term between genotype and exposure. RESULTS: Workers at the highest quartile of the natural log-transformed cumulative endotoxin exposure and with the endotoxin-responsive CD14/-1619 G allele had significantly lower FEV(1) and forced expiratory flow, midexpiratory phase (FEF(25-75)) percent predicted compared with workers with an AA genotype, with no significant differences noted at lower endotoxin levels for either genotype. The gene-environment effect was marked for atopic workers. Laboratory animal allergy, murine allergen exposure, CD14/-159 or -550 genotype, and a gene exposure interaction term for these genotypes and exposures did not predict changes in lung function. CONCLUSIONS: A significant gene-environment interaction affects airways function in laboratory animal workers. More highly endotoxin exposed workers with CD14/-1619G alleles have significantly lower FEV(1) and FEF(25-75) percent predicted than those with CD14/-1619AA alleles. Atopic workers are particularly affected by cumulative endotoxin exposures. PMID- 20579717 TI - Symptom-pattern phenotype and pulmonary function in preschool wheezers. AB - BACKGROUND: Pulmonary function in preschool wheezing phenotypes based on wheeze onset and duration and atopic status has been extensively described but has not been studied in symptom-pattern phenotypes of episodic (viral) and multiple trigger wheeze. OBJECTIVE: We investigated whether multiple-trigger wheezers were more likely to have abnormal pulmonary function and increased fraction of exhaled nitric oxide (FeNO) than episodic (viral) wheezers and whether multiple-breath wash-out was more sensitive at detecting abnormal pulmonary function than specific airways resistance (sR(aw)) in preschool wheezers. METHODS: FeNO, multiple-breath wash-out indices (lung clearance index [LCI] and conductive airways ventilation inhomogeneity [S(cond)]) and sR(aw) were measured in healthy children and those with recurrent wheeze aged 4 to 6 years. Subgroup analysis was performed according to current symptom-pattern (multiple-trigger vs episodic [viral]), atopic status (atopic vs nonatopic), and wheeze status (currently symptomatic vs asymptomatic). RESULTS: Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in S(cond), and 15% (95% CI, 3% to 28%; P = .01) in sR(aw) compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P = .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), S(cond) was abnormal in 68% (95% CI, 61% to 74%), and sR(aw) was abnormal in 26% (95% CI, 16% to 35%) of multiple-trigger wheezers. CONCLUSIONS: Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. S(cond) is the most sensitive indicator of abnormal pulmonary function in preschool wheezers. PMID- 20579718 TI - Indoor pet exposure and the outcomes of total IgE and sensitization at age 18 years. AB - BACKGROUND: Early-life exposure to household pets has been shown to be protective against allergic sensitization in childhood. OBJECTIVE: We sought to evaluate the association between early-life pet exposure and allergic sensitization at age 18 years. METHODS: Teenagers who had been enrolled in the Detroit Childhood Allergy Study birth cohort in 1987-1989 were contacted at age 18 years. Serum total and allergen-specific IgE levels to 7 common allergens (dust mite, cat, dog, ragweed, Timothy grass, Alternaria species, and peanut; atopy was defined as any specific IgE level > or =0.35 kU/L) were measured at age 18 years. Annual interview data from childhood were used to determine indoor dog and cat (> or =50% of their time in the home) exposure during early life. Exposure was considered in various ways: first year, cumulative lifetime, and age groups, as well as multiple pets. RESULTS: Dog or cat exposure in the first year of life was not associated with atopy (relative risk, 0.97; 95% CI, 0.83-1.12). Those living with pets in the first year and atopic at 18 years had lower total IgE levels. Neither cumulative exposure nor exposure at a particular age was strongly and consistently associated with either outcome. Although not statistically significant, there was a pattern of decreased odds of sensitization among those with 2 or more pets versus no pets in the first year of life. CONCLUSIONS: Early-life pet exposure can be associated with lower total IgE levels among atopic subjects but is not strongly associated with decreased likelihood of sensitization to common allergens at age 18 years. PMID- 20579719 TI - Safety of small-particle inhaled corticosteroids in infants. PMID- 20579720 TI - Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine. AB - BACKGROUND: Because influenza vaccine contains some residual egg protein, there is a theoretic risk of anaphylaxis when vaccinating patients with egg allergy. The objective of this study was to estimate the risk of anaphylaxis in children with egg allergy administered an adjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccine (Arepanrix; GlaxoSmithKline, Mississauga, Ontario, Canada). METHODS: Patients with confirmed egg allergy with a history of respiratory or cardiovascular reactions after egg ingestion were vaccinated in 2 divided doses (10% and 90%) administered at a 30-minute interval, whereas children with other types of egg-induced allergic reactions were vaccinated with a single dose. All patients remained under observation for 60 minutes after vaccination. A 24-hour follow-up telephone call was made to detect any delayed reaction. The main outcome was the occurrence of an anaphylactic reaction according to criteria specified by the Brighton Collaboration. RESULTS: Among the 830 patients with confirmed egg allergy, only 9% required the vaccine to be administered in divided doses. No patient had an anaphylactic reaction. Nine patients had minor allergic symptoms treated with an antihistamine (1 in the 60 minutes after vaccination and 8 in the following 23 hours), and 3 others received salbutamol (1 in the first 60 minutes after vaccination). Further vaccination of more than 3600 other children with reported egg allergy caused no anaphylaxis based on the criteria of the Brighton Collaboration, although 2 patients received epinephrine for symptoms compatible with allergy. CONCLUSION: Although anaphylaxis after influenza immunization is a theoretic risk, vaccination of patients with egg allergy with an adjuvanted monovalent pH1N1 influenza vaccine resulted in no cases of anaphylaxis and on that basis appears safe. PMID- 20579721 TI - Structure of coatomer cage proteins and the relationship among COPI, COPII, and clathrin vesicle coats. AB - COPI-coated vesicles form at the Golgi apparatus from two cytosolic components, ARF G protein and coatomer, a heptameric complex that can polymerize into a cage to deform the membrane into a bud. Although coatomer shares a common evolutionary origin with COPII and clathrin vesicle coat proteins, the architectural relationship among the three cages is unclear. Strikingly, the alphabeta'-COP core of coatomer crystallizes as a triskelion in which three copies of a beta' COP beta-propeller domain converge through their axial ends. We infer that the trimer constitutes the vertex of the COPI cage. Our model proposes that the COPI cage is intermediate in design between COPII and clathrin: COPI shares with clathrin an arrangement of three curved alpha-solenoid legs radiating from a common center, and COPI shares with COPII highly similar vertex interactions involving the axial ends of beta-propeller domains. PMID- 20579722 TI - Post-draw PAN-PMMA nanofiber reinforced and toughened Bis-GMA dental restorative composite. AB - OBJECTIVES: The polyacrylonitrile (PAN)-poly(methyl methacrylate) (PMMA) core shell nanofiber reinforced dental composites have been investigated for their excellent interface adhesive, and this kind of novel dental composite has the potential for clinical uses such as denture base resin and crown-bridge material. The first objective of this work was to determine the improving effect of tensile properties by post-drawing PAN-PMMA nanofibers membrane. The second objective was to examine the flexural strength (Fs), flexural modulus (Ey) and work of fracture (WOF) of Bis-GMA/TEGDMA composites reinforced with PAN-PMMA nanofibers. METHODS: PAN(core)-PMMA(shell) nanofiber was made by an electrospinning setup with a high speed rotating rod-like collector. The post-draw process was carried out at 120 degrees C for 5 min, and all the nanofiber membranes were elongated to the desired elongation ratio (30%, 60% or 100%). Tensile properties and flexural properties of both nanofiber membranes and nanofiber reinforced Bis-GMA/TEGDMA composites were investigated. A scanning electron microscope (SEM) was used to observe the fiber morphology and the fracture surface of the composite. A dynamic mechanical thermal analyzer (DMTA) was employed to determine the dynamic mechanical properties such as tandelta and E'. RESULTS: The post-drawing treatment significantly improved the tensile properties and fiber parallelism of nanofiber membranes. The addition of PAN-PMMA nanofibers into Bis-GMA/TEGDMA clearly showed the reinforcement effect; the flexural strength (Fs), flexural modulus (Ey) and work of fracture (WOF) kept rising with the nanofiber mass fraction changing from 0%, 0.6%, 0.8%, 1.0% to 1.2%. The flexural properties of composites reinforced with post-drawn nanofiber were further increased in comparison with those of untreated nanofiber reinforced ones. Also, the SEM observations of the fracture surface of the composites demonstrated good interfacial adhesion between fibers and resin. SIGNIFICANCE: The post-drawing treatment was confirmed as a useful method for significantly increasing the tensile strength (673.4%) and tensile modulus (875.3%) of nanofiber membranes. In addition, the composites reinforced with post-drawn PAN-PMMA nanofibers exhibited higher Fs (13.6%), Ey (5.3%) and WOF (30.4%) than those reinforced with as electrospun PAN-PMMA nanofibers. When 1.2% mass fraction of post-drawn nanofibers were added to Bis-GMA/TEGDMA resin, the Fs, Ey and WOF increased by 51.6%, 64.3% and 152.0%, respectively, compared with neat resin. PMID- 20579723 TI - Dimensions of adolescent subjective social status within the school community: description and correlates. AB - School pupils strive to meet both school-defined and social goals, and the structure of adolescent self-concept is multidimensional, including both academic and non-academic self-perceptions. However, subjective social status within the school community has been represented as a single dimension. Scottish 15-year olds participating in a school-based survey (N = 3194) rated their own status, compared to their school year-group, via images of seven 10-rung ladders. These generated a very high response rate, and factor analysis distinguished three dimensions: (1) ladders representing "popular", "powerful", "respected", "attractive or stylish" and "trouble-maker"; (2) "doing well at school" and "[not] a trouble-maker"; and (3) "sporty". Unique relationships with variables representing more objective and/or self-report behavioural measures suggest these dimensions are markers of "peer", "scholastic" and "sports" status. These analyses suggest multiple dimensions of adolescent social hierarchy can be very simply measured and contribute towards the development of more robust instruments within this area. PMID- 20579724 TI - Mathematically defined tissue engineering scaffold architectures prepared by stereolithography. AB - The technologies employed for the preparation of conventional tissue engineering scaffolds restrict the materials choice and the extent to which the architecture can be designed. Here we show the versatility of stereolithography with respect to materials and freedom of design. Porous scaffolds are designed with computer software and built with either a poly(D,L-lactide)-based resin or a poly(D,L lactide-co-epsilon-caprolactone)-based resin. Characterisation of the scaffolds by micro-computed tomography shows excellent reproduction of the designs. The mechanical properties are evaluated in compression, and show good agreement with finite element predictions. The mechanical properties of scaffolds can be controlled by the combination of material and scaffold pore architecture. The presented technology and materials enable an accurate preparation of tissue engineering scaffolds with a large freedom of design, and properties ranging from rigid and strong to highly flexible and elastic. PMID- 20579725 TI - The use of immobilized neurotrophins to support neuron survival and guide nerve fiber growth in compartmentalized chambers. AB - We answered two major questions: (1) does retrograde signaling involve retrograde transport of nerve growth factor (NGF); and (2) is a gradient of immobilized NGF sufficient to promote and guide local axonal growth? To answer these questions, we developed a technique that resulted in stably immobilized NGF and combined this with compartmented chambers. NGF was photochemically-immobilized on a chitosan surface either in the cell body (CB) compartment, distal axon (DA) compartment, or both. Neuron survival and axon outgrowth were found to be insignificantly different from positive controls where soluble NGF was present. When NGF was immobilized on chitosan surfaces in the DA compartment, and in the absence of soluble NGF, neuron survival was observed, likely due to the retrograde signal of the activated TrkA receptor and NGF-induced signals, but not the retrograde signal of NGF itself. Axons were guided towards the higher end of the step concentration gradient of NGF that was photoimmobilized on the chitosan surface in the DA compartment by laser confocal patterning, demonstrating axonal guidance. These studies provide better insight into NGF signaling mechanisms which are important to both understanding developmental disorders and degenerative diseases of the nervous system, as well as improving design strategies to promote nerve regeneration after injury. PMID- 20579726 TI - Degradable, pH-sensitive, membrane-destabilizing, comb-like polymers for intracellular delivery of nucleic acids. AB - This report describes the design and synthesis of a new series of degradable, pH sensitive, membrane-destabilizing, comb-like polymers that can enhance the intracellular delivery of therapeutic nucleic acids. These comb-like polymers are based on a diblock polymer backbone where the first block is a copolymer of pH sensitive ethyl acrylic acid (EAA) monomers and hydrophobic butyl methacrylate (BMA) or hexyl methacrylate monomers. The second block is a homopolymer of N acryloxy succinimide (NASI) or ss-benzyl l-aspartate N-carboxy-anhydride (BLA NCA) monomers, which are functionalized to allow controlled grafting of hydrophobic HMA and cationic trimethyl aminoethyl methacrylate (TMAEMA) copolymers via acid-labile hydrazone linkages. These comb-like polymers displayed high hemolytic activity in acidic solutions, which increased with the increase in polymer concentration. All comb-like polymers degraded into small fragments upon incubation in an acidic solution (pH 5.8) due to hydrolysis of the hydrazone linkages connecting the hydrophobic/cationic grafts to the polymer backbone. Comb like polymers successfully complexed anti-GAPDH siRNA molecules into serum- and nuclease-stable particles, which successfully silenced GAPDH expression at both the mRNA and protein levels. These results collectively indicate the potential of these new comb-like polymers to serve as vehicles for effective intracellular delivery of therapeutic nucleic acids. PMID- 20579727 TI - Actions of the anti-cancer drug suberoylanilide hydroxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures. AB - Micro- and nanotechnologies are increasingly being applied in cancer research. Here we report the effects of an experimental breast cancer agent, SAHA, on the cytoarchitecture and adherence of MDA-MB-231 metastatic human breast cancer cells on flat silicon surfaces and in three dimensional (3-D) isotropic silicon microstructures. The 3-D silicon microstructure were fabricated using a single mask and single etch step process to yield arrays of star- and circular-shaped microchambers 151-168 microm in diameter and 53-68 microm deep. There was a marked expansion of the microtubule network, an increase in mean cell area and mean cell length in response to SAHA. SAHA also decreased the nuclear-to cytoplasmic area (N/C). Atomic force microscopy (AFM) showed there was no change in cellular elasticity over the nuclear region in response to SAHA. The alterations in cytoarchitecture produced by SAHA were associated with changes in the mode of adhesion of the cells in silicon microstructures. In contrast to control cells which conformed to the microstructures, SAHA caused cells to stretch and attach to the microstructures through actin-rich cell extensions. We conclude that isotropically etched silicon microstructures comprise microenvironments that discriminate metastatic mammary cancer cells in which cytoskeletal elements reorganized in response to the anti-cancer agent SAHA. PMID- 20579728 TI - Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites. AB - In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and thereby enhancing their orientation with a consequently highly ordered neuronal cell matrix, which may have strong bearings on the elucidation of regeneration mechanisms. PMID- 20579729 TI - Human corneal epithelial cell response to epidermal growth factor tethered via coiled-coil interactions. AB - The development of new strategies for protein immobilization to control cell adhesion, growth and differentiation is of prime interest in the field of tissue engineering. Here we propose a versatile approach based on the interaction between two de novo designed peptides, Ecoil and Kcoil, for oriented immobilization of epidermal growth factor (EGF) on polyethylene terephthalate (PET) films. After amination of PET surfaces by ammonia plasma treatment, Kcoil peptides were covalently grafted in an oriented fashion using succinimidyl 6-[30 (2-pyridyldithio)-propionamido] hexanoate (LC-SPDP) linker, and the Kcoil functionalized films were characterized by X-ray photoelectron spectroscopy (XPS). Bioactivity of Ecoil-EGF captured on Kcoil-functionalized PET via coiled coil interactions was confirmed by EGF receptor phosphorylation analysis following A-431 cell attachment. We also demonstrated cell biological effects where tethered EGF enhanced adhesion, spreading and proliferation of human corneal epithelial cells compared to EGF that was either physically adsorbed or present in solution. Tethered EGF effects were most likely linked to the prolonged activation of both mitogen-activated protein kinase and phosphoinositidine 3-kinase pathways. Taken together, our results indicate that coiled-coil-based oriented immobilization is a powerful method to specifically tailor biomaterial surfaces for tissue engineering applications. PMID- 20579730 TI - A surface crosslinked UHMWPE stabilized by vitamin E with low wear and high fatigue strength. AB - Wear particle-induced periprosthetic osteolysis has been a clinical problem driving the development of wear resistant ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacement. Radiation crosslinking has been used to decrease wear through decreased plastic deformation; but crosslinking also reduces mechanical properties including fatigue resistance, a major factor limiting the longevity of joint implants. Reducing UHMWPE wear with minimal detriment to mechanical properties is an unaddressed need for articular bearing surface development. Here we report a novel approach to achieve this by limiting crosslinking to the articular surface. The antioxidant vitamin E reduces crosslinking efficiency in UHMWPE during irradiation with increasing concentration, thus we propose to spatially control the crosslink density distribution by controlling the vitamin E concentration profile. Surface crosslinking UHMWPE prepared using this approach had high wear resistance and decreased crosslinking in the bulk resulting in high fatigue crack propagation resistance. The interface region did not represent a weakness in the material due to the gradual change in the crosslink density. Such an implant has the potential of decreasing risk of fatigue fracture of total joint implants as well as expanding the use of UHMWPE to younger and more active patients. PMID- 20579731 TI - The mechanisms of cytotoxicity of urethane dimethacrylate to Chinese hamster ovary cells. AB - Monomers released from resin-containing products may cause various adverse effects. Urethane dimethacrylate (UDMA) is a principal resin monomer and also a major component released from various dental resin materials. Thus the toxic effects and mechanisms should be elucidated for improving of its safety use. Here we investigated the effects of UDMA on the growth, cell cycle progression, reactive oxygen species (ROS) production and glutathione (GSH) alteration in CHO K1 cells, and the preventive effects by antioxidants (NAC and catalase) were also evaluated. UDMA elicited growth inhibition (>0.025 mm) of CHO-K1 cells in a clearly dose-dependent manner. Cell cycle perturbation and ROS overproduction were also observed. A 0.1 mm UDMA-induced S-phase cell cycle arrest and ROS accumulation. Cell apoptosis and necrosis became significant when UDMA concentration was 0.25 mm. GSH depletion occurred at cells treated with 0.25 mm UDMA, a highly cytotoxic concentration at which point myriad cells were under apoptosis or necrosis. Thus GSH depletion can be crucial for the death of CHO-K1 cells. Furthermore NAC (0.5-10 mm) and catalase (250-1000 U/ml) obviously attenuated the UDMA-induced toxicity by reducing ROS generation and cell cycle disturbance, and the effects were dose-related. These results suggest that UDMA toxicity is associated with ROS production, GSH depletion, cell cycle disturbance and cell apoptosis/necrosis. PMID- 20579732 TI - Involvement of preprotachykinin A gene-encoded peptides and the neurokinin 1 receptor in endotoxin-induced murine airway inflammation. AB - Tachykinins encoded by the preprotachykinin A (TAC1) gene such as substance P (SP) and neurokinin A (NKA) are involved in neurogenic inflammatory processes via predominantly neurokinins 1 and 2 (NK1 and NK2) receptor activation, respectively. Endokinins and hemokinins encoded by the TAC4 gene also have remarkable selectivity and potency for the NK1 receptors and might participate in inflammatory cell functions. The aim of the present study was to investigate endotoxin-induced airway inflammation and consequent bronchial hyper-reactivity in TAC1(-/-), NK1(-/-) and also in double knockout (TAC1(-/-)/NK1(-/-)) mice. Sub acute interstitial lung inflammation was evoked by intranasal Escherichia coli lipopolysaccharide (LPS) in the knockout mice and their wildtype C57BL/6 counterparts 24 h before measurement. Respiratory parameters were measured with unrestrained whole body plethysmography. Bronchoconstriction was induced by inhalation of the muscarinic receptor agonist carbachol and Penh (enhanced pause) correlating with airway resistance was calculated. Lung interleukin-1beta (IL 1beta) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured with ELISA. Histological evaluation was performed and a composite morphological score was determined. Myeloperoxidase (MPO) activity in the lung was measured with spectrophotometry to quantify the number of infiltrating neutrophils/macrophages. Airway hyper-reactivity was significantly reduced in the TAC1(-/-) as well as the TAC1(-/-)/NK1(-/-) groups. However, LPS-induced histological inflammatory changes (perivascular/peribronchial oedema, neutrophil infiltration and goblet cell hyperplasia), MPO activity and TNF-alpha concentration were markedly diminished only in TAC1(-/-) mice. Interestingly, the concentrations of both cytokines, IL-1beta and TNF-alpha, were significantly greater in the NK1(-/-) group. These data clearly demonstrated on the basis of histology, MPO and cytokine measurements that TAC1 gene-derived tachykinins, SP and NKA, play a significant role in the development of endotoxin-induced murine airway inflammation, but not solely via NK1 receptor activation. However, in inflammatory bronchial hyper-responsiveness other tachykinins, such as hemokinin 1 acting through NK1 receptors also might be involved. PMID- 20579733 TI - Monitoring copper toxicity in natural phytoplankton assemblages: application of Fast Repetition Rate fluorometry. AB - Four experiments were conducted with natural coastal phytoplankton assemblages exposed to [Cu] within the range 5-80 microg L(-1). The effect of Cu on several biological variables such as chlorophyll a concentration, particle size distribution, O2-production and fluorescence variables recorded by a Fast Repetition Rate fluorometer was monitored during 72 h. Variable fluorescence (Fv) was the most sensitive and rapid among all the variables tested. This work contributes to reinforce the use of fluorescence endpoints in ecotoxicological studies by proving their ecological relevance through relationships found between fluorescence and population-level responses as growth rate and gross O2 production. The lowest calculated EC10 was 2.65 microg L(-1), concentration commonly exceeded in polluted waters. PMID- 20579734 TI - Comparative toxicity of leachates from 52 textiles to Daphnia magna. AB - The environmental aspects of textiles are very complex and include production, processing, transport, usage, and recycling. Textiles are made from a variety of materials and can contain a large number of chemicals. Chemicals are used during production of fibres, for preservation and colouring and they are released during normal wear and during washing. The aim of this study was to investigate the release to water of toxic chemicals from various textiles. Altogether 52 samples of textiles made from cotton (21), linen (4), cotton and linen (7), cellulose (3), synthetic fibres (7), cotton and synthetic fibres (8) and wool (2). Seven were eco-labelled. All textiles were cut into squares and placed into Petri dishes with 50 ml ISO test medium in a concentration series (4-256 cm(2)/50 ml) and tested for acute toxicity to Daphnia magna. Estimated EC50s were converted into weight/volume, and 48-h EC50s ranged between <1 and >182 g/L. It was not possible to detect any difference between fibre type and toxicity (ANOVA), but a significantly higher toxicity was found for printed versus unprinted cotton and cotton/linen textiles, while the opposite was found for synthetic textiles. Eco labelled products were evenly distributed on a toxicity scale, which means that eco-labelling in its present form does not necessarily protect users or the environment from exposure to toxic chemicals. Therefore, the results from the present study suggest that bioassays and toxicity tests should become an integrated part of textile environmental quality control programs. PMID- 20579735 TI - Diet and particularly seafood are major sources of perfluorinated compounds in humans. AB - Commercially used perfluorinated compounds (PFCs) have been widely detected in wildlife and humans, but the sources of human exposure are not fully characterized. The objectives of this study were to explore possible associations between concentrations of PFCs in serum and consumption of food with particular focus on seafood, and to compare estimated dietary intakes with determined serum PFC concentrations. Concentrations of 19 PFCs were determined in serum from 175 participants in the Norwegian Fish and Game Study and evaluated with respect to food consumption using multiple linear regression analysis. Associations between estimated individual total dietary intakes of PFCs and serum concentrations were also explored. PFC concentrations in serum were significantly associated (p<0.05) with the consumption of lean fish, fish liver, shrimps and meat, as well as age, breastfeeding history and area of residence (R(2) 0.35-0.63). The estimated dietary intakes of perfluorooctanoic acid (PFOA), perfluoroundecanoic acid (PFUnDA) and perfluorooctane sulfonic acid (PFOS) were 0.60, 0.34 and 1.5 ng/kg body weight/day, respectively. Seafood (fish and shellfish) was the major dietary source contributing 38% of the estimated dietary intakes of PFOA, 93% of PFUnDA and 81% of PFOS. The estimated dietary intakes of these three selected PFCs were significantly associated with the corresponding serum PFC concentrations (p<0.05). In conclusion, our results show that consumption of fish and shellfish is a major determinant of serum PFC concentrations. Further, significant relationships between estimated dietary intakes and serum concentrations have been demonstrated for the first time. PMID- 20579736 TI - Accumulation of background levels of persistent organochlorine and organobromine pollutants through the soil-earthworm-hedgehog food chain. AB - The bioaccumulation of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and DDT and metabolites, was investigated in the soil-earthworm-hedgehog food chain. Concentrations of selected POPs were measured in soil and earthworms collected in grassland and open woodland and in hair and blood of hedgehogs foraging in two parks containing these habitats. Despite background concentrations in soil (ranging from 1.3 to 9.3 ng/g for DDTs, 2.3 to 6.5 ng/g for PCBs and 0.08 to 0.20 ng/g for PBDEs), biota-soil accumulation factors (BSAFs) indicated that earthworms accumulated POPs (0.48-1.70 for DDTs, 1.09-2.76 for PCBs and 1.99-5.67 for PBDEs) and that animals feeding on earthworms are potentially exposed to higher concentrations of pollutants. BSAFs decreased with increasing soil concentrations for the three groups of compounds, suggesting that steady-state equilibrium was not reached in soil or earthworms. Positive, but low, log-linear relationships were found for DDT (r(2)=0.23, p<0.05 for Brasschaat and r(2)=0.63, p<0.01 for Hoboken) and PCB (r(2)=0.13, p<0.05 for both parks) concentrations between soil and earthworms. In order to relate earthworm to hedgehog POP concentrations, the foraging behavior of each individual was taken into account. The use of hair as a potential biomonitoring tissue in exposure and risk assessment of POPs was evaluated by examining the relationship between PCB and p,p'-DDE levels in hedgehogs' hair and blood. Contaminant profiles were used to gain insight into biotransformation of the studied compounds in each step of the investigated food chain and in the blood of hedgehogs, as well as the consequences thereof for their incorporation in hair. The absence of a discernable relationship between POP concentrations in earthworms and hair is possible due to variation in individual foraging behavior and POP uptake. Our results suggest that POPs in tissues should be measured from an adequate number of individuals per population instead of relying on indirect estimates from levels in soil or prey items. PMID- 20579737 TI - Monitoring of firefighters exposure to smoke during fire experiments in Portugal. AB - Forest fires represent a serious threat to public security in Europe due to the large burned area. Moreover, smoke pollution due to forest fire events is an important public health issue for the communities directly affected, and particularly for the personnel involved in firefighting operations. Aiming to contribute to the scientific knowledge concerning firefighters exposure to forest fires smoke, data of individual exposure to carbon monoxide, nitrogen dioxide, volatile organic compounds, and particulate matter were obtained during experimental field fires for a group of 10 firefighters equipped with portable "in continuum" measuring devices. Measured values are very high exceeding the Occupational Exposure Standard limits, in particular for peak limit thresholds. These are the first measurements and analysis of firefighter's individual exposure to toxic gases and particles in fire smoke experiments in Europe. However, they already indicate that urgent measures to avoid these levels of exposure are needed. PMID- 20579739 TI - Surgical results in the management of advanced primary congenital glaucoma in a rural pediatric population. AB - OBJECTIVE: To present the anatomic and functional results of surgical treatment for advanced primary congenital glaucoma (PCG) in a rural setting. DESIGN: Retrospective, observational case series. PARTICIPANTS: Forty eyes of 22 consecutive patients diagnosed with PCG and who underwent surgical treatment. METHODS: All eyes underwent surgical treatment for PCG. Type of surgery and postoperative complications were noted. We examined anatomic and functional indices before and after the operation. MAIN OUTCOME MEASURES: Visual acuity (VA), intraocular pressure (IOP), refractive spherical error, cup-to-disc ratio (CDR), and horizontal corneal diameter (HCD). RESULTS: Average age at the time of surgery was 3.3 years (range, 0.4-10) and the mean follow-up was 6 months (range, 1-11). 15% showed marked lens dislocation owing to the severe buphthalmos at presentation. Preoperative IOP was 54 +/- 2 mmHg, HCD was 15.1 +/- 0.3 mm, and CDR (when visible) was 0.8 +/- 0.02. Surgical intervention included 31 trabeculotomies, 6 Ahmed Glaucoma Valve implants, 1 goniotomy, and 2 eviscerations. Serious complications were noted in 4 eyes. Final postoperative IOP was 23 +/- 2 mmHg (P < 0.0001). Patients were significantly more likely to have ambulatory VA (following objects or better) after operation (18% vs 64%; P < 0.0001). CONCLUSIONS: Our surgical outcomes in children with advanced PCG demonstrated moderate overall improvement in IOP and modest improvement of VA. Deep deprivation amblyopia, severe disease manifestation at presentation, opaque corneas, and frequent lens dislocation limited the possible success. These data further signify the need for effective, timely screening of children and prompt recognition by health care workers to reduce the rate of avoidable blindness in developing countries. PMID- 20579738 TI - Recombinant form of human wild type mannan-binding lectin (MBL/A) but not its structural variant (MBL/C) promotes phagocytosis of zymosan by activating complement. AB - Mannan-binding lectin (MBL) mediates innate immune responses, such as activation of the complement lectin pathway and phagocytosis, to help fight infections. In the present study, employing recombinant forms of human MBL (rMBL), the role of wild type MBL (rMBL/A) and its structural variant rMBL/C in mediating THP-1 phagocytosis of fluorescent-labeled zymosan was examined and compared to MBL purified from human plasma (pMBL/A). Flow cytometric analyses revealed that opsonization of zymosan with rMBL/A and pMBL/A (0.5-30microg/ml) resulted in a 1.9- and 2.7-fold enhancement in its uptake by THP-1 cells in the presence of serum that was depleted of both MBL and the classical pathway component, C1q (MBL/C1q Dpl serum). In contrast, no enhancement in phagocytosis was observed when zymosan was opsonized with rMBL/C. Addition of MBL monoclonal antibody, EDTA, or mannan to the opsonization reaction mixture inhibited THP-1 phagocytosis of pMBL/A opsonized zymosan. Heat inactivation of MBL/C1q Dpl serum abolished the 2-fold increase in phagocytosis and in the absence of serum the direct opsonic activity of MBL did not contribute significantly to the uptake of zymosan into THP-1 cells. Activation products of complement components C3 and C4 were deposited on zymosan opsonized with pMBL/A and rMBL/A but not rMBL/C indicating that MBL-mediated phagocytosis of zymosan requires activation of the complement lectin pathway. The findings imply that impaired MBL-mediated phagocytosis may put individuals homozygous for the mutant allele MBL/C but not wild type MBL/A at increased risk to infections such as yeast. PMID- 20579740 TI - Human pro-islet amyloid polypeptide (ProIAPP(1-48)) forms amyloid fibrils and amyloid spherulites in vitro. AB - Deposition of beta sheets of islet amyloid polypeptide (IAPP) in pancreatic tissue is implicated in the aetiology of type 2 diabetes mellitus (T2DM). IAPP is cleaved from its precursor protein, pro-islet amyloid polypeptide (ProIAPP) and incomplete cleavage results in ProIAPP(1-48), which is found co-deposited with IAPP. Cu(II) prevents IAPP from forming amyloid and herein we investigated if it would also prevent ProIAPP(1-48) from forming beta sheets. Excess Cu(II) prevented ProIAPP(1-48) from forming amyloid and additionally reversed the formation of beta sheets in pre-formed fibrils of the peptide. The latter was also true for ProIAPP(1-48) fibrils formed in the presence of Al(III). An unexpected finding was the formation of spherulites of ProIAPP(1-48) which were only observed in preparations which included Al(III). The spherulites were 40-100 microm in diameter and stained positively for Al(III) suggesting a role for this metal in their formation. The abolition by Cu(II) of the propensity of ProIAPP(1 48) to form amyloid may have important implications for the treatment of T2DM. The immediate significance for diabetes of the equally novel observation of spherulites of ProIAPP(1-48) is unknown though, as with spherulites of Abeta(42) in Alzheimer's disease, there may be implications for the aetiology of the disease. PMID- 20579741 TI - Second-tier natural antidepressants: review and critique. AB - The use of Complementary and Alternative Medicine (CAM) for physical and mental problems has increased significantly in the US over the past two decades, and depression is one of the leading indications for the use of CAM. This article reviews some of the lesser-known natural products with potential psychiatric applications that are starting to emerge with some scientific and clinical evidence and may constitute a next wave of natural antidepressants: Rhodiola rosea, chromium, 5-Hydroxytryptophan (5-HTP) and inositol. Background information, efficacy data, proposed mechanisms of action, recommended doses, side effects, and precautions are reviewed. We found some encouraging data for the use of these natural products in specific populations of depressed patients. R. rosea is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects. Chromium has a beneficial effect on eating-related atypical symptoms of depression, and may be a valuable agent in treating atypical depression and seasonal affective disorder. Inositol may be useful in the treatment of bipolar depression when combined with mood stabilizers. Evidence for the clinical efficacy of 5-HTP is also promising but still preliminary. Although more well-designed and larger controlled studies are needed before any substantive conclusions can be drawn, the available evidence is compelling and these natural products deserve further investigation as a possibly significant addition to the antidepressant armamentarium. PMID- 20579742 TI - Upper alpha activity during working memory processing reflects abnormal inhibition in major depression. AB - BACKGROUND: EEG studies examining 'resting' state (i.e. non-task) state brain activity in major depressive disorder (MDD) have reported numerous abnormalities within the alpha bandwidth. These findings are discussed extensively within affective disorders literature but their relationship to functional aspects of depressive psychopathology remains unclear. Investigating alpha modulation during active cognitive processing may provide a more targeted means of relating aberrant alpha activity to specific aspects of depression symptomatology. Alpha activity is reliably modulated during working memory (WM) processing and WM impairments are a common neuropsychological consequence of MDD. Moreover, it has been suggested that alpha activity reflects internally mediated inhibitory process and attenuated inhibition has been suggested to contribute to WM inefficacy. AIM: The current investigation examined whether alpha was modulated differently in MDD participants during WM processing and whether the pattern of alpha activity was consistent with impairments in inhibitory processes. METHOD: Event related synchronisation (ERS) within the upper alpha band over the retention interval of a modified Sternberg WM task was examined in 15 acutely depressed and 15 never depressed right-handed female participants. RESULTS: MDD participants displayed greater upper alpha ERS than controls during the online information maintenance component of WM processing. This was evident over left, but not right, parieto-occipital cortex. CONCLUSION: The results are consistent with increased inhibition of extraneous material during WM processing in depression. This may reflect a neurobiological compensation strategy whereby additional neural resources are required to achieve comparable performance accuracy during effortful cognitive processing in MDD. PMID- 20579743 TI - Clinical utility of Standardised Assessment of Personality - Abbreviated Scale (SAPAS) among patients with first episode depression. AB - BACKGROUND: Personality disorder frequently co-occurs with depression and seems to be associated with a poorer outcome of treatment and increased risk for recurrences. However, the diagnosing of personality disorder can be lengthy and requires some training. Therefore, a brief screening interview for comorbid personality disorder among patients suffering from depression would be of clinical use. METHOD: The present study aimed to assess the utility of the Standardised Assessment of Personality - Abbreviated Scale (SAPAS) as a screen for personality disorder in a population of patients recently diagnosed with first episode depression. A total number of 394 patients with an ICD-10 diagnosis of a single depressive episode were sampled consecutively via the Danish Psychiatric Central Research Register during a 2years inclusion period and assessed by the screening interview and, subsequently, by the Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: We found, that a cut-off of 3 on the screen correctly identified the presence of comorbid personality disorder in 73.1% of the patients. The sensitivity and specificity were 0.80 and 0.70, respectively. LIMITATIONS: The findings cannot be generalized to patients outside hospital settings. CONCLUSION: The study provides evidence for the clinical utility of SAPAS as a screening interview for comorbid personality disorder in a population of patients with a primary diagnosis of depression. PMID- 20579744 TI - A polymorphism in the microRNA-30e precursor associated with major depressive disorder risk and P300 waveform. AB - BACKGROUND: Growing evidence shows that the etiological causes and pathological processes underlying major depressive disorder (MDD) and schizophrenia (SCZ) overlap. Our previous study revealed a strong association between the polymorphism ss178077483 in the miRNA-30e precursor (pre-miR-30e) and the risk of SCZ. We thus hypothesized that this SCZ risk allele at the pre-miR-30e gene also confers risk of MDD. METHODS: To explore the relationship between miR-30e ss178077483 and MDD, we conducted an association analyses in 1088 MDD patients and 1102 control subjects from the Han Chinese population. We also determined the effects of miR-30e ss178077483 on the development of P300 event-related potential components induced by an auditory odd-ball task. RESULTS: We detected a statistically significant positive association between miR-30e ss178077483 and MDD (allelic P=0.0287; genotypic P=0.0275). Moreover, the P300 latency was associated with miR-30e ss178077483 genotypes and the individuals with the C/T genotype have a longer P300 latency than those carrying the C/C genotype (P=0.009). LIMITATIONS: Larger numbers of subjects and different ethnic groups would confirm and strengthen these preliminary findings. CONCLUSIONS: To our knowledge, this is the first evidence to suggest that miRNA polymorphisms may play an important role in MDD susceptibility. These findings also imply that certain miRNAs may be involved in the etiology of MDD. PMID- 20579745 TI - Cellular immune responses in cetaceans immunized with a porcine erysipelas vaccine. AB - Clinical erysipelas represents a significant health problem in managed cetacean species. Vaccination was suspended in many oceanariums in the past due to losses associated with vaccine-induced hypersensitivities which were deemed to be a greater threat than clinical erysipelas. A perceived shift in clinical presentation of erysipelas from a chronic dermatologic form to an acute systemic form in dolphins sparked interest in re-initiating vaccination with improved subunit vaccines of Erysipelothrix rhusiopathiae. This manuscript describes the development and application of in vitro correlates of immunity (T(H)1, T(H)2 and T(REG)) in Tursiops truncatus induced by immunization with a commercial porcine 65 kDa subunit E. rhusiopathiae vaccine. Variable degrees of pre-existing T cell memory were identified prior to vaccination. Vaccine-induced IFN gamma responses were consistent with a T(H)1 response and associated with elimination of erysipelas in all vaccinated animals. Comparative analysis between six-month and 12-month vaccination booster regimes demonstrated maintenance of superior memory in the six-month group; however, anamnestic responses induced by booster were only identified in the 12-month group. To our knowledge, this is the first study to develop and apply advanced immunologic analyses for assessing vaccine efficacy in captive or free-ranging wildlife. PMID- 20579746 TI - TNF-alpha-dependent regulation of CXCR3 expression modulates neuronal survival during West Nile virus encephalitis. AB - The chemokine CXCL10 exerts antiviral effects within the central nervous system (CNS) through the recruitment of virus-specific T cells. However, elevated levels of CXCL10 may induce neuronal apoptosis given its receptor, CXCR3, is expressed by neurons. Using a murine model of West Nile virus (WNV) encephalitis, we determined that WNV-infected neurons express TNF-alpha, which down-regulates neuronal CXCR3 expression via signaling through TNFR1. Down-regulation of neuronal CXCR3 decreased CXCL10-mediated calcium transients and delayed Caspase 3 activation. Loss of CXCR3 activation, via CXCR3-deficiency or pretreatment with TNF-alpha prevented neuronal apoptosis during in vitro WNV infection. These results suggest that neuronal TNF-alpha expression during WNV encephalitis may be an adaptive response to diminish CXCL10-induced death. PMID- 20579748 TI - Risk factors of all-cause in-hospital mortality among Korean elderly bacteremic urinary tract infection (UTI) patients. AB - Urinary tract infection (UTI) is the most frequent cause of bacteremia/sepsis in elderly people and increasing antimicrobial resistance in uropathogens has been observed. To describe the characteristics of bacteremic UTI in elderly patients and to identify the independent risk factors of all-cause in-hospital mortality, a retrospective cohort study of bacteremic UTI patients of age over 65 was performed at a single 2000-bed tertiary hospital. Bacteremic UTI was defined as the isolation of the same organism from both urine and blood within 48 h. Eighty six elderly bacteremic UTI patients were enrolled. Community-acquired infection was the case for most patients (79.1%), and Escherichia coli accounted for 88.6% (70/79) among Gram-negative organisms. Non-E. coli Gram-negative organisms were more frequent in hospital-acquired cases and male patients while chronic urinary catheter insertion was related with Gram-positive urosepsis. The antibiotic susceptibility among Gram-negative organisms was not different depending on the source of bacteremic UTI, while non-E. coli Gram-negative organisms were less frequently susceptible for cefotaxime, cefoperazone/sulbactam, and aztreonam. All cause in-hospital mortality was 11.6%, and functional dependency (adjusted hazard ratio=HR=10.9, 95% confidence interval=95%CI=2.2-54.6) and low serum albumin (adjusted HR=27.0, 95%CI=2.0-361.2) were independently related with increased all cause in-hospital mortality. PMID- 20579747 TI - Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. AB - Dopamine D(2) receptor antagonism is a unifying property of all antipsychotic drugs in use for schizophrenia. While often effective at ameliorating psychosis, these drugs are largely ineffective at treating negative and cognitive symptoms. Increasing attention is being focused on the complex genetics of the illness and the signaling pathways implicated in its pathophysiology. We review targeted approaches for pharmacotherapy involving the glutamatergic, GABAergic and cholinergic pathways. We also describe several of the major genetic findings that identify signaling pathways representing potential targets for novel pharmacological intervention. These include genes in the 22q11 locus, DISC1, Neuregulin 1/ErbB4, and components of the Akt/GSK-3 pathway. PMID- 20579749 TI - Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats. AB - BACKGROUND: Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. METHODS: Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17beta-oestradiol (E2) supplements (10 MUg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). RESULTS: In oophorectomised rats plasma levels of E2 declined from 1301 +/- 80 to 196 +/- 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ~60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 +/- 2.0 to 6.0 +/- 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 +/- 1.2% to 18.1 +/- 2.3%, p<0.05), increased SBP (from 82 +/- 4.2 to 97 +/- 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. CONCLUSION: Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved. PMID- 20579750 TI - Atherosclerotic plaques induced by marble-burying behavior are stabilized by exercise training in experimental atherosclerosis. AB - BACKGROUND: We assessed the hypothesis whether behavioral stress may affect the development of atherosclerosis and whether regular exercise training may influence the composition of atherosclerotic plaques in apolipoprotein (apo) E deficient mice. METHODS: Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Exercise training (45 min swimming, 3 times/week) was conducted, and behavioral stress was provoked by glass marble-burying procedure. Mice were treated with marble-burying, marble-burying behavior plus swimming training, and swimming alone over 8 weeks. RESULTS: Exercise training decreased the atherosclerotic lesions, but marble-burying behavior increased the lesions. The plaques containing macrophage accumulation with intercellular adhesion molecule-1 (ICAM-1) expression associated with reduced collagen contents were induced in the mice treated with marble-burying. However, ICAM-1 expression was suppressed and collagen contents were reversed in the mice that received marble-burying behavior plus exercise training. In addition, exercise alone and concomitant exercise training reduced the superoxide production in aortic walls, shown by dihydroethidium staining, compared with that in mice with marble-burying behavior alone. There were no significant differences in the serum lipids profiles among the groups. CONCLUSIONS: Behavioral stress increased the atherosclerotic lesions and induced the adhesion molecule expression with superoxide production on the lesions in apo E-deficient mice. Exercise training may stabilize plaque lesions induced by marble-burying behavior in this animal model. PMID- 20579751 TI - Usefulness of the MOSAIC (measurement of stenosis by aliasing coronary flow) method using transthoracic color Doppler echocardiography in unstable angina patients. AB - BACKGROUND: The aim of this study was to investigate the significance of the MOSAIC (measurement of stenosis by aliasing coronary flow) method for the detection of proximal left coronary stenosis in patients with unstable angina (UA) using transthoracic Doppler echocardiography (TTDE). METHODS: Patients (n=107) with UA were evaluated. Proximal left coronary flow was sought in the short axis (SAX) at the aortic root level using color Doppler guidance. When detected coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. Then, the color baseline was shifted until the color flow showed "isovelocity". RESULTS: Proximal coronary flow was detected in 86 (80.4%) of 107 patients. In these 86 patients, an optimal cutoff value of isovelocity >= 47.5 cm/s predicted significant coronary stenosis (percent diameter stenosis >= 70%) of the proximal left anterior descending (AHA segment 6) or left main coronary artery with a sensitivity of 88%, specificity of 97%, positive predictive value of 98%, and negative predictive value of 86%. In all 107 patients, the same cutoff value predicted significant coronary stenosis with a sensitivity of 78%, specificity of 98%, positive predictive value of 98%, and negative predictive value of 81%. CONCLUSIONS: The MOSAIC method may play a complementary role in expeditious risk stratification and decision making in patients with UA. PMID- 20579752 TI - Serum levels of soluble receptor for advanced glycation end products (sRAGE) in Takayasu's arteritis. PMID- 20579753 TI - Mechanisms of variability of left ventricular outflow tract gradient in hypertrophic cardiomyopathy. PMID- 20579754 TI - A simulation model for the potential spread of foot-and-mouth disease in the Castile and Leon region of Spain. AB - A spatial stochastic model was used to simulate the spread of a foot-and-mouth disease (FMD) epidemic in the Castile-and-Leon (CyL) region of Spain. The model was fitted using information available on premises demographics and on assumptions for animal movements, indirect contacts, and airborne exposure. Control measures dictated by Spanish and European Union regulations constituted a reference strategy to which six alternative control strategies were compared. For the reference strategy, the median (95% PI) numbers of infected, depopulated, and quarantined premises were 141 (2-1099), 164 (4-1302), and 334 (31-2059), respectively. Depopulation and vaccination of premises within a radius of <1km and <3km, respectively, around infected premises significantly (p-value<0.001) decreased the number of infected premises, compared to the reference scenario. Results presented here will contribute to the revision, design, and implementation of contingency plans and programs for prevention and control of FMD epidemics in Spain. PMID- 20579755 TI - Caring for and caring about: disentangling the caregiver effect and the family effect. AB - Besides patients' health and well-being, healthcare interventions may affect the well-being of significant others. Such 'spill over effects' in significant others may be distinguished in two distinct effects: (i) the caregiving effect and (ii) the family effect. The first refers to the welfare effects of providing informal care, i.e., the effects of caring for someone who is ill. The second refers to a direct influence of the health of a patient on others' well-being, i.e., the effects of caring about other people. Using a sample of Dutch informal caregivers we found that both effects exist and may be comparable in size. Our results, while explorative, indicate that economic evaluations adopting a societal perspective should include both the family and the caregiving effects measured in the relevant individuals. PMID- 20579756 TI - Comparison of efficacy and toxicity of short-course carbon ion radiotherapy for hepatocellular carcinoma depending on their proximity to the porta hepatis. AB - BACKGROUND AND PURPOSE: To compare the efficacy and toxicity of short-course carbon ion radiotherapy (C-ion RT) for patients with hepatocellular carcinoma (HCC) in terms of tumor location: adjacent to the porta hepatis or not. MATERIALS AND METHODS: The study consisted of 64 patients undergoing C-ion RT of 52.8 GyE in four fractions between April 2000 and March 2003. Of these patients, 18 had HCC located within 2 cm of the main portal vein (porta hepatis group) and 46 patients had HCC far from the porta hepatis (non-porta hepatis group). We compared local control, survival, and adverse events between the two groups. RESULTS: The 5-year overall survival and local control rates were 22.2% and 87.8% in the porta hepatis group and 34.8% and 95.7% in the non-porta hepatis group, respectively. There were no significant differences (P=0.252, P=0.306, respectively). Further, there were no significant differences in toxicities. Biliary stricture associated with C-ion RT did not occur. CONCLUSIONS: Excellent local control was obtained independent of tumor location. The short-course C-ion RT of 52.8 GyE in four fractions appears to be an effective and safe treatment modality in the porta hepatis group just as in the non-porta hepatis group. PMID- 20579757 TI - Tibialis anterior muscle fatigue leads to changes in tibial axial acceleration after impact when ankle dorsiflexion angles are visually controlled. AB - Heel impact forces may lead to injury as they travel through the human musculoskeletal system. Previous work on the effect that localized muscle fatigue has on the tibial response (shank axial acceleration) to impact was limited because ankle angle was not controlled. The purpose of this study was to compare the tibial response when the tibialis anterior was fatigued and when not fatigued, while participants controlled dorsiflexion angles at impact using visual feedback. Twenty participants (10 male, 10 female; M+/-SD=21.8+/-2.9 years) were strapped supine to a human pendulum apparatus, and instrumented with a low mass accelerometer (affixed medial to the tibial tuberosity). Participant dorsiflexion angle range was recorded by an electro-goniometer, and divided into four angle ranges so tibial response variables (peak tibial acceleration, time to peak acceleration, acceleration slope) could be compared when fatigued and not fatigued. Peak tibial acceleration and acceleration slopes decreased, and time to peak acceleration increased following fatigue, when comparing values across the same dorsiflexion ranges. Dorsiflexion angle alone did not account for differences in tibial response during localized leg muscle fatigue; supporting prior work and suggesting that the muscle and ankle joint become less stiff when fatigued, thereby increasing the lower extremity attenuation capability to heel impacts. PMID- 20579758 TI - Circadian rhythms in handwriting kinematics and legibility. AB - The aim of the present study was to analyze the circadian rhythmicity in handwriting kinematics and legibility and to compare the performance between Dutch and German writers. Two subject groups underwent a 40 h sleep deprivation protocol under Constant Routine conditions either in Groningen (10 Dutch subjects) or in Berlin (9 German subjects). Both groups wrote every 3h a test sentence of similar structure in their native language. Kinematic handwriting performance was assessed with a digitizing tablet and evaluated by writing speed, writing fluency, and script size. Writing speed (frequency of strokes and average velocity) revealed a clear circadian rhythm, with a parallel decline during night and a minimum around 3:00 h in the morning for both groups. Script size and movement fluency did not vary with time of day in neither group. Legibility of handwriting was evaluated by intra-individually ranking handwriting specimens of the 13 sessions by 10 German and 10 Dutch raters. Whereas legibility ratings of the German handwriting specimens deteriorated during night in parallel with slower writing speed, legibility of the Dutch handwriting deteriorated not until the next morning. In conclusion, the circadian rhythm of handwriting kinematics seems to be independent of script language at least among the two tested western countries. Moreover, handwriting legibility is also subject to a circadian rhythm which, however, seems to be influenced by variations in the assessment protocol. PMID- 20579759 TI - Development of a structure-based model for the competitive growth of Listeria innocua in minced chicken breasts. AB - Most predictive models are based on planktonic microbial growth in broth and, therefore, do not deal with diffusional limitations generated by the solid-food structure. Recently, a few approaches have incorporated the diffusional component, but still on the basis of pure cultures growing in homogenous supports. In this work, a transport-phenomenon model that considers the complex and dynamic structure of real foods, as well as its background microflora, has been developed. This structure-based model was applied to the competitive growth of Listeria innocua in minced chicken breasts, considering oxygen as the limiting substrate. Physical structure and microbial growth in minced meat were compared to those reported for meat-based kappa-carrageenan gels by means of scanning electron microscopy (SEM) and viable counts. In both systems, microbial growth was affected by diffusional limitations, as compared with broth cultures. However, significant differences in their physical structure and a key effect of the indigenous microflora and the meat tissue itself, resulted in different extent and distribution of microbial growth. The approach here developed, useful for food safety purposes, has been shown to provide a reasonably good simulation of experimental data in minced breasts. PMID- 20579760 TI - Focus. PMID- 20579761 TI - Hepatitis C virus replication cycle. PMID- 20579762 TI - The NF-kappaB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes. AB - BACKGROUND & AIMS: The pro-inflammatory functions of NF-kappaB must be tightly regulated to prevent inappropriate tissue damage and remodelling caused by activated inflammatory and wound-healing cells. The p50 subunit of NF-kappaB is emerging as an important repressor of immune and inflammatory responses, but by mechanisms that are poorly defined. This study aims to delineate p50 target genes in activated hepatic stellate cells and to outline mechanisms utilised in their repression. METHODS: Hepatic stellate cells were isolated from nfkb1(p50) deficient or Wt mice and gene expression compared using microarray. Target genes were verified by qRT-PCR and p50-mediated HDAC-1 recruitment to the target genes demonstrated using chromatin immunoprecipitation. RESULTS: We identify p50 as transcriptional repressor of multiple pro-inflammatory genes including Ccl2, Cxcl10, Gm-csf, and Mmp-13. These genes are over-expressed in nfkb1(p50) deficient mice suffering from chronic hepatitis and in fibrogenic/inflammatory hepatic stellate cells isolated from nfkb1(-/-) liver. We identify Mmp-13 as a bona-fide target gene for p50 and demonstrate that p50 is required for recruitment of the transcriptional repressor histone deacetylase (HDAC)-1 to kappaB sites in the Mmp-13 promoter. Chromatin immunoprecipitations identified binding of HDAC-1 to specific regulatory regions of the Ccl2, Cxcl10, Gm-csf genes that contain predicted kappaB binding motifs. Recruitment of HDAC-1 to these genes was not observed in nfkb1(-/-) cells suggesting a requirement for p50 in a manner similar to that described for Mmp-13. CONCLUSIONS: Recruitment of HDAC-1 to inflammatory genes provides a widespread mechanism to explain the immunosuppressive properties of p50. PMID- 20579763 TI - Lower SCD expression in dendritic cells compared to macrophages leads to membrane lipids with less mono-unsaturated fatty acids. AB - Macrophages and dendritic cells originate from a common myeloid precursor. Although several studies compared transcriptional profiles of these cells, not a single study compared their lipid profiles. Therefore, we measured and compared fatty acid (FA) and phospholipid (PL) species composition of granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL 4) and macrophage colony-stimulating factor (M-CSF) differentiated monocytes isolated from healthy volunteers. We found that these two cell types prominently differ in their FA composition. Dendritic cells (DCs) contain lower proportions of C16 and C18 mono-unsaturated FAs, but higher proportions of C20 and C22 poly unsaturated fatty acids (PUFAs) than phagocytic macrophages. Analysis of PL species profiles revealed that GM-CSF/IL-4 differentiated cells have increased amounts of longer and more desaturated phospatidylethanolamine (PE) and phosphatidylserine (PS) species, but lower amounts of shorter and less desaturated PE and PS species than M-CSF differentiated cells. These cell type specific lipid profiles can be attributed to a differential expression and activity of stearoyl-CoA desaturase (SCD). Taken together, our results show that GM-CSF/IL-4 compared to M-CSF differentiated monocytes have less mono-unsaturated FA and PL species, which are due to lower SCD activity observed in DCs. PMID- 20579764 TI - NALP3 is not necessary for early protection against experimental tuberculosis. AB - In vitro, Toll-like receptors (TLR)2, 4 and 9 as well as NOD-like receptor 2 critically determine macrophage responses to Mycobacterium tuberculosis (Mtb) infection. However, in low-dose experimental murine tuberculosis, single or multiple deficiencies in TLRs 2, 4, 9 or NOD2 have little, if any, impact on early mycobacterial growth containment, granuloma formation and survival. Here, we analyzed the relevance of NALP3, one component of the danger-signaling inflammasome, for (i) Mtb-induced cytokine secretion in vitro and in vivo, (ii) restriction of Mtb replication in infected organs and (iii) granuloma formation. In the absence of functional NALP3, there was no IL-1beta and IL-18 production in Mtb-infected dendritic cells and macrophages in vitro, whereas secretion of IL 1alpha, IL-12p40 and TNF remained unaffected. After three weeks of infection, NALP3-deficient as well as IL-18-deficient mice were as capable as wildtype mice of restricting Mtb loads at a plateau level within well-differentiated granulomas. In conclusion, despite its involvement in cytokine processing, NALP3 is not essential for induction of protective immunity to Mtb. PMID- 20579765 TI - Differences in lipopolysaccharide-induced signaling between conventional dendritic cells and macrophages. AB - Dendritic cells (DCs) and macrophages contribute to the activation of immune responses against infectious agents. They sense the presence of microbes through germline-encoded pattern-recognition receptors (PRRs), which recognize pathogen associated molecular patterns (PAMPs). Among the different PAMPs, the response to lipopolysaccharide (LPS) is one of the best characterized. Upon LPS encounter DCs undergo an activation process and acquire the ability to prime both natural killer and T-cell responses after migration to lymph nodes. Once they completed the effector phase, DCs reach a terminal differentiation stage and eventually die by apoptosis. By contrast, macrophages do not leave the tissue upon LPS recognition. They first initiate inflammatory processes and then switch to an anti-inflammatory phenotype to restore tissue homeostasis. In this review we will focus on the molecular bases of the divergent responses of DCs and macrophages to LPS. PMID- 20579766 TI - Initial receptor-ligand interactions modulate gene expression and phagosomal properties during both early and late stages of phagocytosis. AB - The receptors engaged during recognition and phagocytic uptake of microorganisms and particles influence signaling events and diverse subcellular responses that occur during phagosome formation and maturation. However, pathogens generally have multiple ligands on their surface, making it difficult to dissect the roles of individual receptors during phagocytosis. Moreover, it remains elusive to which extent receptor-ligand interactions and early binding events define the subsequent intracellular fate of phagosomes. Here, we used latex beads coupled to single ligands, focusing on immunoglobulin G, mannan, bacterial lipopolysaccharides and avidin, and monitored: (1) phagocytic uptake rates, (2) fusion of phagosomes with lysosomal compartments, (3) the gene expression profile during phagocytosis, (4) the protein composition of mature phagosomes and (5) time-dependent dynamics of protein association with phagosomes in J774.A1 mouse macrophages. The differently coated latex beads were internalized at different rates and exhibited different kinetics of phagolysosomal fusion events dependent on their specific ligand. Furthermore, less than 60% of identified phagosomal proteins and only 10-15% of changes in gene expression were common to all investigated ligands. These findings demonstrate that each single ligand induced a distinct pattern of genes and a different protein composition of phagosomes. Taken together, our data argue that phagocytic receptor-specific programs of signaling events direct phagosomes to different physiological states and support the existence of a specific receptor-ligand 'signature' during the whole process of phagocytosis. PMID- 20579767 TI - Metabolic profiling to determine the cause of the increased triphenyltetrazolium chloride reduction in mannitol-treated maize callus. AB - When Zea mays callus cultures of two different genotypes were treated with the osmoticum mannitol (0.53M) for 24h their ability to reduce the tetrazolium derivative 2,3,5-triphenyltetrazolium chloride (TTC) to form the insoluble red compound formazan is stimulated. The formazan can be extracted with 95% ethanol for quantitation and this reaction has been used as a measure of viability since only live cells can carry out this reduction. In order to determine the cause of the increased TTC reduction caused by mannitol we carried out metabolic profiling analysis using GC-MS to identify 80 compounds. There were increases in sugar alcohols, hexoses except fructose and in total sugars. The total organic acid pools did not change and nitrogen containing compounds decreased slightly. Principle component analysis showed a large treatment effect due to changes in carbohydrate and nitrogen metabolism. These results indicate that the increased carbohydrate available for the citric acid cycle may be the cause of the increased TTC reduction observed after the mannitol treatment. PMID- 20579768 TI - [Spectral domain optical coherence tomography in inflammatory disease]. PMID- 20579769 TI - [Human limbal epithelial cell growth kinetics in vitro]. AB - PURPOSE: To assess limbal epithelial cell growth kinetics in vitro using tissue retrieved from organ-cultured donor corneas. PATIENTS AND METHODS: Twenty-one limbal explants were retrieved from corneoscleral rims of donor corneal grafts preserved for 18-24 days in organ culture. The explants were cultured at 37 degrees C for 10, 13, or 18 days. The epithelial cell sheet area was measured during culture by means of morphometry. At the end of culture, the dissociated cells were counted and analyzed by immunocytochemistry. RESULTS: The curve of the epithelial cell sheet area (S) in relation to culture time (t) was best fitted by a polynomial model (S=0.024t(3) - 0.038t(2) - 0.044t + 0.092). The average duration of the cell cycle was 24h. Cell growth decreased as donor tissue retrieval postmortem time increased. Cultured cells featured various expressions of cytokeratin-3 ranging from absent (few cells) to strong. More than 50% of cells expressed vimentin. CONCLUSION: Limbal tissue retrieved from donor tissue that was organ-cultured for 3 weeks maintains a potential for cell renewal and growth compatible with clinical use for limbal allograft transplantation or cultured stem cell transplantation. However, cell growth potential is impaired by donor postmortem ischemia, which implies that tissue must be retrieved as soon as possible after donor death. PMID- 20579770 TI - Repeated prevalence surveys of healthcare-associated infections in Finnish neonatal intensive care units. AB - More than one-fifth of patients in neonatal intensive care units (NICUs) have been reported to suffer from healthcare-associated infections (HAIs). The aim of this study was to assess prevalence, onset and types of HAI in Finnish NICU patients. We conducted six monthly point-prevalence surveys in all Finnish NICUs (N=24) between November 2008 and May 2009. For all patients present on the day of survey, the underlying conditions and invasive devices or treatments used on the day of survey and during the preceding six days were recorded on standardised forms. All HAIs active or under treatment on the day of survey were included. HAIs were categorised into early-onset (onset within the first 72 h of life) and late-onset (onset after the first 72 h of life) infections. During the six surveys, 1281 forms were obtained. Among them, 164 HAIs in 163 patients were identified (overall prevalence, 13%); 63 (38%) of the HAIs were late-onset infections (prevalence, 6.5%). Main types of HAI were clinical sepsis, laboratory confirmed bloodstream infection, conjunctivitis, and pneumonia. Of all HAIs, 24% were microbiologically confirmed. Patients with birth weight <1500 g suffered from late-onset HAIs more commonly than those with birth weight > or =1500 g (10% vs 4%, P<0.01). Also hospitalisation of > or =7 days was associated with increased prevalence of HAI (8% vs 3%, P=0.01). The study was useful in terms of increasing awareness of HAI in the participating NICUs. These results can be used to strengthen incidence surveillance of HAIs in the Finnish NICUs in the future. PMID- 20579771 TI - Assessing specific secondary ICD-9-CM codes as potential predictors of surgical site infections. AB - BACKGROUND: Public reporting and reduced Medicare payments because of health care associated infections have resulted in the consideration of administrative discharge codes as markers of health care-associated infections. This study aims to determine whether specific secondary ICD-9-CM infection codes linked to cases from a large data set of surgical procedures are predictors of surgical site infections (SSIs). METHODS: All patients undergoing 1 of 9 surgical procedures from January 1, 2005, through December 31, 2005, at a large academic medical center and who were assigned a secondary ICD-9-CM infection code at discharge were eligible for study inclusion. All cases were reviewed to determine the presence of SSIs. Logistic regression was used to determine which secondary codes were predictors of SSIs. RESULTS: Among 75 secondary infection codes applied at discharge to 454 patients, only 1 code (998.59) appeared to be reliably associated with SSIs. Two other general infection codes (996.63 and 996.67) and 1 specific infection code (320.3) may also have utility. CONCLUSION: Administrative coding data do not perform well to identify SSIs. Some general secondary infection codes, however, may have the potential to be utilized in screening algorithms of electronic health data to assist in SSI surveillance. PMID- 20579772 TI - Diurnal variation in hand hygiene compliance in a tertiary level multidisciplinary intensive care unit. AB - BACKGROUND: Hand hygiene compliance among health care providers is considered to be the single most effective factor to reduce hospital acquired infections. Despite continuous education and awareness, compliance with hand hygiene guidelines has remained low, particularly during evening shifts. OBJECTIVE: Our objective was to determine the compliance with hand hygiene guidelines among doctors, nurses, and paramedical staff during day and night duties in a multidisciplinary intensive care unit (ICU). METHODS: We used a prospective, observational, 6-month study conducted in a 34-bed ICU within a tertiary care teaching hospital. All doctors, nurses, and paramedical staff in the ICU were included. An investigator, placed within the ICU setting, observed the hand hygiene practices during day and night. Day and night shift change times were 08:00 and 20:00 hours, respectively. RESULTS: Of the 5639 opportunities for hand hygiene, 3383 (59.9%) were properly performed. Overall rates of compliance were 66.1% for doctors, 60.7% for nurses, and 38.6% for paramedical staff. Hand hygiene compliance dropped during the night for doctors (81% vs 46%, respectively, P < .001), for nurses (64% vs 55%, respectively, P = .02), and for paramedical staff (44% vs 31%, respectively, P = .01). Characterization of noncompliance is as follows: "No handwashing after procedure" in 41%, "improper duration of handwashing" in 32%, and "no handwashing done at all" in 27% of the events. "No handwashing done at all" occurred in 55% of the time at night with doctors having the highest rate of noncompliance, making 163 (34%) contacts without handwashing. CONCLUSION: Whereas compliance with hand hygiene guidelines was lower at night compared with day, irrespective of discipline in all 3 groups of health care providers, both periods of compliance would benefit from additional training focusing on the importance of hand hygiene around the clock. PMID- 20579774 TI - [Neuroimaging: technical aspects and practice]. AB - Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging. PMID- 20579773 TI - Carvedilol as a potential novel agent for the treatment of Alzheimer's disease. AB - Oligomeric beta-amyloid (Abeta) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective beta-adrenergic receptor blocker, significantly attenuates brain oligomeric beta-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable "learning" thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD. PMID- 20579775 TI - [Interpretive reading of the non-fermenting gram-negative bacilli antibiogram]. AB - Among non-fermenting Gram-negative rods, the most clinically important species are Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, which are frequently multiresistant. P. aeruginosa resistance to beta-lactams depends on the production of chromosomal and plasmid-mediated beta lactamases, altered permeability (loss of OprD porin is related to carbapenem resistance) and active efflux systems, particularly MexAB-OprM. In aminoglycoside resistant strains, the main mechanism of resistance is the production of modifying enzymes; the efflux pump MexXY-OprM is also involved. Quinolone resistance in P. aeruginosa is related to changes in topoisomerases, altered permeability and efflux pumps. Multiresistance in A. baumannii may be associated with the acquisition of resistant islands carrying different resistant determining factors. Several broad- and extended-spectrum beta-lactamases have been shown in this microorganism, however the main mechanism of resistance to betalactams is the hyperproduction of the chromosomal cephalosporinase (AmpC) related to the presence of the ISAba1 in the promoter region of this gene. The main mechanism of resistance to carbapenems is the acquisition of carbapenemases type B (metallo-beta-lactamases) or class D (oxacillinases), however the loss of a porin can also contribute to modulate the final MIC. The resistance to aminoglycosides has been associated with the production of modifying enzymes or the overexpression of efflux pump (AdeABC), whereas the resistance to quinolones is related to changes in the protein targets as well to the overexpression of efflux pump(s). S. maltophilia show resistance to beta-lactams including carbapenems due to the production of two beta-lactamases (L-1 and L-2). Aminoglycoside-modifying enzymes have also been described in this species. In contrast to that observed in other organisms, S. maltophilia resistance to quinolones has been mainly related to active efflux, rather than to targets alterations. PMID- 20579777 TI - [Rapid influenza diagnostic tests for detection of novel influenza A (H1N1) virus in children]. AB - INTRODUCTION: Accuracy of rapid BD Directigen((r)) EZ Flu A+B diagnostic test against Influenza A (H1N1) Virus in children. METHODS: A descriptive retrospective study was performed. One hundred and forty children underwent the rapid influenza test and the RT-PCR against Influenza A (H1N1) Virus. RESULTS: The sensitivity was 70.4% (95% CI: 58.9-79.7), specificity 100 % (95% CI: 94.7 100), NPV 76.6% (95% CI: 66.9-84,2) and PPV 100% (95% CI: 92.8-100). CONCLUSION: This test showed high sensitivity and specificity, very similar to the seasonal influenza, in children. PMID- 20579776 TI - [Pericardial effusion associated to interferon in an immunocompetent patient]. PMID- 20579778 TI - [Which antibiotics should we report in an antibiogram, and how?]. AB - The information provided in the individual susceptibility reports (antibiograms) is clinically and epidemiologically relevant, and is an important tool for antibiotic stewardship. The selection of the most appropriate antimicrobial agents to be included in the reports should be decided by each Clinical Microbiology laboratory after consulting with the departments most involved in the clinical management of infectious diseases. The clinical interest of the drugs should be the most important variable to consider; thus, reported antibiotics should have demonstrated clinical efficacy. Other variables to consider are local prevalence (in the hospital, areas of the hospital), the cost, the approved indications, and the most recent clinical guidelines regarding the drugs of choice and alternative agents. Certain antibiotics may only be reported in specific circumstances (selective reporting), which should be decided by each laboratory according to their local circumstances. It may be necessary to adapt the information provided according to the microorganism and suspected location of the infection. In some cases, it is convenient to include additional written comments or observations with the aim of helping clinicians to choose. In this review we include a proposal for our country that should be adapted to local situations. PMID- 20579779 TI - [Bleeding lesion in the cervix of a woman infected with human immunodeficiency virus (HIV)]. PMID- 20579780 TI - [Interpretive reading of enterobacteria antibiograms]. AB - The resistance pattern observed in the antibiogram of an isolate should be the sum of its natural resistance pattern, characteristic of the species, plus the acquired resistances. In Enterobacteriaceae, the production of inactivating enzymes is the main mechanism of resistance to beta-lactams and aminoglycosides. Each one of these enzymes recognizes one or more specific beta-lactams or aminoglycosides as substrate. This substrate specificity implies a specific resistance pattern from which we can deduce the enzymes present in the isolate. However, enzymatic-mediated resistance is not the only mechanism implicated and resistance is frequently multifactorial. Resistance to quinolones is mainly due to precise, sequential chromosomal mutations that can be selected by fluoroquinolone treatments. Recently, certain plasmid-mediated genes which code enzymes that modify quinolones or that are target protectors have been implicated in the low level resistance to quinolones. PMID- 20579781 TI - [Acute encephalopathy and mononucleosis syndrome associated with tuberculosis chemoprophylaxis]. PMID- 20579782 TI - Synthesis of some 3-substituted amino-4,5-tetramethylene thieno[2,3-d][ 1,2,3] triazin-4(3H)-ones as potential antimicrobial agents. AB - A series of 3-substituted amino-4,5-tetramethylene thieno[2,3-d] [1,2,3]-triazine 4(3H)-ones have been synthesized and characterized by UV,IR, 1H NMR, elemental and mass spectral analysis. The title compounds were evaluated for their antimicrobial activity by agar diffusion method against four bacteria and three fungi using Ampicillin and Miconazole nitrate as standards. The compounds VIIIa, IXa, Xa and XIa showed an antimicrobial efficacy considerably greater than the compounds Ia to VIIa with -H, phenyl and electron donating (activating) groups like methyl, ethyl and tolyl substitutions at R, suggesting that lipophillic groups like chloro, fluoro substitution on the phenyl ring plays an important role in enhancing the antimicrobial properties of this class of compounds. From the screening results it can be concluded that the compounds having the lipophillic groups like chlorophenyl and fluorophenyl groups at R exhibited appreciable antimicrobial activities. Whereas, the compounds are having -H, phenyl and electron donating (activating) groups like methyl, ethyl and tolyl substituents at R were less active against all the organisms used. PMID- 20579783 TI - Effect of flavonoids on the Abeta(25-35)-phospholipid bilayers interaction. AB - Amyloid-beta peptide (Abeta) is the major component of amyloid deposits found in the brain tissue of Alzheimer patients. The tendency of amyloid peptide to form amyloid plaques is known to be related to the features of the plasma membrane. Flavonoids, a group of naturally occurring molecules, exert beneficial properties to human health thanks to their antioxidant property; this property depends on their capacity to interact and permeate the cell membrane lipid bilayer. In the present research we report an Electron Paramagnetic Resonance (EPR) investigation of 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes interacting with the beta-amyloid fragment Abeta(25-35), in the presence of flavonoids rutin, quercetin, naringin and naringenin. Our results, evidencing a flavonoid-dependent rigidifying effect of the bilayer, may provide the molecular basis to explain the known neuroprotective effect of flavonoid compounds. PMID- 20579784 TI - [Mercury poisoning]. AB - Mercury is a widespread heavy metal with potential severe impacts on human health. Exposure conditions to mercury and profile of toxicity among humans depend on the chemical forms of the mercury: elemental or metallic mercury, inorganic or organic mercury compounds. This article aims to reviewing and synthesizing the main knowledge of the mercury toxicity and its organic compounds that clinicians should know. Acute inhalation of metallic or inorganic mercury vapours mainly induces pulmonary diseases, whereas chronic inhalation rather induces neurological or renal disorders (encephalopathy and interstitial or glomerular nephritis). Methylmercury poisonings from intoxicated food occurred among some populations resulting in neurological disorders and developmental troubles for children exposed in utero. Treatment using chelating agents is recommended in case of symptomatic acute mercury intoxication; sometimes it improves the clinical effects of chronic mercury poisoning. Although it is currently rare to encounter situations of severe intoxication, efforts remain necessary to decrease the mercury concentration in the environment and to reduce risk on human health due to low level exposure (dental amalgam, fish contamination by organic mercury compounds...). In case of occupational exposure to mercury and its compounds, some disorders could be compensated in France. Clinicians should work with toxicologists for the diagnosis and treatment of mercury intoxication. PMID- 20579785 TI - [Current treatment of multiple sclerosis]. AB - Since commercialisation of the first immunomodulatory drug (IMD) for multiple sclerosis (subcutaneous interferon beta-1b) in 1995, three new IMD have been on the market: two interferons (intramuscular interferon beta-1a and subcutaneous interferon beta-1a) and glatiramer acetate. These four immunomodulatory drugs have a similar efficiency: they reduce by about 30% the relapse rate of treated patients compared to untreated patients. Their effect on disability is moderate mainly due to the reduced relapse rate. Lately, in 2002, mitoxantrone was approved for aggressive relapsing-remitting MS and in 2007 the first monoclonal antibody (natalizumab) was approved for active relapsing-remitting MS. PMID- 20579786 TI - Congenital benign teratoma of the tongue with bifid tip, ankyloglossia and polydactyly: report of a case. AB - Teratomas of the tongue are rare, and often accompany other anomalies within the head and neck. We describe a combination of anomalies in a 6-week-old infant with teratoma and bifid tip of the tongue, severe tongue tie, and polydactyly. The teratoma was excised and the tongue tie released with no complications. PMID- 20579787 TI - Biomechanics of the transverse carpal arch under carpal bone loading. AB - BACKGROUND: Carpal tunnel release and conservative interventions are widely used in clinical therapies of carpal tunnel syndrome. The efficacy of these treatment and interventions mainly lies in the exploitation of the mechanical properties of carpal tunnel. This study investigated the structural mechanics of the transverse carpal arch using cadaveric hands. METHODS: Paired force was applied to the insertion sites of the transverse carpal ligament at both the distal (hamate trapezium) and proximal (pisiform-scaphoid) levels of the carpal tunnel. The two pairs of forces were simultaneously applied in an inward or outward direction when the transverse carpal ligament was intact and transected. Transverse carpal arch and carpal tunnel compliance in response to the forces were analyzed. Three way repeated measures ANOVA were used to examine the effect of the transverse carpal ligament status (intact/transected), the level of the carpal tunnel (distal/proximal) and the force application direction (inward/outward) on the biomechanics of the transverse carpal arch. FINDINGS: Transverse carpal ligament plays a stabilizing role in resisting outward deformation of the carpal tunnel. The carpal tunnel at the proximal level is more flexible than the carpal tunnel at the distal level. The carpal tunnel is more compliant under the inward force application than under the outward force application. INTERPRETATION: The understanding of carpal tunnel mechanics potentially helps to improve the existing strategies and to develop alternatives for the treatment of carpal tunnel syndrome. PMID- 20579788 TI - A root exudates based approach to assess the long-term phytoavailability of metals in biosolids-amended soils. AB - Organic acids present in the rhizosphere of growing plants are widely recognized to be responsible for dissolving the solid phase metals in the soil and making them available for plant absorption. We proposed a root exudates-based model to assess the long-term phytoavailability of metals in biosolids-amended soils. The phytoavailability of biosolids-borne metals was defined in terms of a capacity factor and an intensity factor. The plant available metal pool, C(0) (capacity factor, mgkg(-1)), can be estimated by fitting the successive organic acids extraction data to an exponential decay kinetic equation. The field metal removal rate, k (intensity factor, yr(-1)), can be estimated from the successive extraction-based metal release rate through an effective annual organic acid production in the rhizosphere which was found to be characteristic of plant species. The protocol was successfully used to assess the long-term phytoavailability of metals in biosolids-amended soil from two biosolids land application sites. PMID- 20579790 TI - A meta-analysis of the effects of psychotherapy with adults sexually abused in childhood. AB - This paper presents the results of a meta-analysis of the treatment outcome studies of different types of psychotherapeutic approaches for adults sexually abused as children. There were 44 studies included comprising 59 treatment conditions, and most of the studies aimed to treat the psychological effects of childhood sexual abuse. Separate meta-analyses were conducted according to study design and outcome domain, in keeping with meta-analytic conventions. For most outcome domains, there was remarkable consistency in overall effect sizes across study design. Effect sizes were predominantly of moderate magnitude for post traumatic stress disorder or trauma symptoms (g=0.72-0.77), internalizing symptoms (g=0.68-0.72), externalizing symptoms (g=0.41-0.53), self-esteem (g=0.56 0.58), and global functioning or symptoms (g=0.57-0.60). Studies measuring interpersonal functioning outcomes had inconsistent effect sizes across study design. Effects were largely maintained at follow-up, although relatively few studies provided follow-up data. A number of moderating variables were examined given the inherent heterogeneity of the studies. Moderator analysis revealed a variety of variables, particularly treatment characteristics, that were associated with better outcomes. However, different variables were identified for the diverse outcomes that were measured, emphasizing the importance of moderator analysis in looking beyond overall treatment effects to ascertain specific elements that confer additional benefit in therapy for the diverse psychological effects of child sexual abuse. PMID- 20579789 TI - Dysregulation in level of goal and action identification across psychological disorders. AB - Goals, events, and actions can be mentally represented within a hierarchical framework that ranges from more abstract to more concrete levels of identification. A more abstract level of identification involves general, superordinate, and decontextualized mental representations that convey the meaning of goals, events, and actions, "why" an action is performed, and its purpose, ends, and consequences. A more concrete level of identification involves specific and subordinate mental representations that include contextual details of goals, events, and actions, and the specific "how" details of an action. This review considers three lines of evidence for considering that dysregulation of level of goal/action identification may be a transdiagnostic process. First, there is evidence that different levels of identification have distinct functional consequences and that in non-clinical samples level of goal/action identification appears to be regulated in a flexible and adaptive way to match the level of goal/action identification to circumstances. Second, there is evidence that level of goal/action identification causally influences symptoms and processes involved in psychological disorders, including emotional response, repetitive thought, impulsivity, problem solving and procrastination. Third, there is evidence that the level of goal/action identification is biased and/or dysregulated in certain psychological disorders, with a bias towards more abstract identification for negative events in depression, GAD, PTSD, and social anxiety. PMID- 20579791 TI - The clinical significance of creativity in bipolar disorder. AB - Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity-BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity-BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype. PMID- 20579792 TI - The meaning of "control" for childbearing women in the US. AB - Childbearing women, healthcare providers, and commentators on birth broadly identify control as an important issue during childbirth; however, control is rarely defined in literature on the topic. Here we seek to deconstruct the term control as used by childbearing women to better understand the issues and concepts underpinning it. Based on qualitative interviews with 101 parous women in the United States, we analyze meanings of control within the context of birth narratives. We find these meanings correspond to five distinct domains: self determination, respect, personal security, attachment, and knowledge. We also find ambivalence about this term and concept, in that half our sample recognizes "you cannot control birth". Together, these findings call into question the usefulness of the term for measuring quality or improving maternity care and highlight other concepts which may be more fruitfully explored. PMID- 20579793 TI - The tradeoff between centralized and decentralized health services: evidence from rural areas in Mexico. AB - This study investigates the effectiveness of centralized and decentralized health care providers in rural Mexico. It compares provider performance since both centralized and decentralized providers co-exist in rural areas of the country. The data are drawn from the 2003 household survey of Oportunidades, a comprehensive study of rural families from seven states in Mexico. The analyses compare out-of-pocket health care expenditures and utilization of preventive care among rural households with access to either centralized or decentralized health care providers. This study benefits from differences in timing of health care decentralization and from a quasi-random distribution of providers. Results show that overall centralized providers perform better. Households served by this organization report less regressive out-of-pocket health care expenditures (32% lower), and observe higher utilization of preventive services (3.6% more). Decentralized providers that were devolved to state governments in the early 1980s observe a slightly better performance than providers that were decentralized in the mid-1990s. These findings are robust to decentralization timing, heterogeneity in per capita government health expenditures, state and health infrastructure effects, and other confounders. PMID- 20579794 TI - Substance abuse and mental health disparities: comparisons across sexual identity groups in a national sample of young Australian women. AB - A growing body of research amply documents health disparities related to substance abuse among sexual minority women. However, relatively little research has examined risk factors or predictors of substance use in this population and even less has explored differences among sexual minority subgroups. Using data from 8850 women aged 25-30 years in the 2003 survey of the Australian Longitudinal Study on Women's Health Survey (ALSWH) we compared rates of substance use (alcohol, marijuana and other illicit drugs) and potential predictors (e.g., depression, anxiety, perceived stress, lower levels of social support) across four sexual identity groups-exclusively heterosexual, mainly heterosexual, bisexual and lesbian. Using statistical weighting of the sample and controlling for demographic characteristics we fitted logistic regression models to estimate adjusted odds ratios for substance use. Compared with exclusively heterosexual women sexual minority women reported significantly higher levels of substance use-but there was notable variation among the three sexual minority subgroups. Women who identified as mainly heterosexual were significantly more likely than exclusively heterosexual women to report at-risk drinking and those who identified as bisexual were more likely to report marijuana use. Mainly heterosexual and bisexual women were also more likely to report binge drinking. Findings implicate stress as an important predictor of substance use and emphasize the need for research that more systematically examines the relationships between minority stress and substance use in sexual minority women. Findings of variations in risk across sexual minority subgroups suggest prevention and intervention strategies aimed at reducing health disparities should be targeted toward specific sexual minority subgroups. PMID- 20579795 TI - Can arts projects improve young people's wellbeing? A social capital approach. AB - Community arts projects are widely believed to have positive impacts on health, wellbeing and social inclusion. Such beliefs underpinned the UK Government-funded SingUp programme for children. Drawing on data from participant observation, extended interviews, focus groups and a questionnaire survey, we examine the experiences of children in three SingUp choirs. We focus specifically on social and emotional wellbeing as they relate to social capital: this being one of the key pathways through which arts participation is thought to impact on health and wellbeing more widely. For many (particularly girls from relatively privileged backgrounds), the experience has been largely positive, providing opportunities to develop social capital, make new friends and build confidence. However, others' experiences have been more equivocal, entailing risks of disconnection from existing networks of friends. We argue that, while arts projects can impact positively on young people's social and emotional wellbeing, we cannot assume that the changes will be unequivocally good or straightforward. We follow Bourdieu and other critical theorists in arguing that social capital operates in association with economic and cultural capital, and cannot be understood in isolation from the wider constraints of people's lives. PMID- 20579796 TI - Rethinking measurement of neighborhood in the context of health research. AB - Systematic social observations have been gaining increasing recognition in neighborhood and health research as a way of measuring neighborhood attributes hypothesized to affect residents' well-being. Despite the growing popularity of this methodology, there has not been a critical discussion of potential shortcomings of this approach. This paper reviews some of the challenges and limitations in the systematic social observations methodology. We especially differentiate between limitations related to the methodology itself and challenges the approach presents for researchers in the field. We conclude by offering directions for future research utilizing this technique. PMID- 20579797 TI - Use of biomedical obstetric care in rural Tanzania: the role of social and material inequalities. AB - Despite over 20 years of efforts to improve maternal health, complications of pregnancy and childbirth continue to threaten women's lives in many countries of sub-Saharan Africa. To reduce maternal mortality levels and achieve Millennium Development Goal Five, institutions working for safe motherhood are committed to making biomedical obstetric care more available to women during childbirth. However, implementation of this strategy is not reaching women at the lower end of the socioeconomic spectrum for reasons that are not well understood. Using data from fieldwork conducted between September 2007 and June 2008, this study examines women's use of biomedical obstetric care in two rural districts of south central Tanzania where this care was being supplied. Specifically, it seeks to explain how social and material inequalities affect decisions and behaviors related to childbirth. In addressing this aim we employed a mixed-methods study design. Effects of sociodemographic characteristics on obstetric care use were examined with logistic regression analysis (n = 1150), while perspectives and experiences of childbearing women were explored with participant observation and in-depth interviews (n = 48). The results from quantitative and qualitative study components were interpreted in light of each other. Statistically significant social and material factors related to use of care included ethnicity, education, parity, and household assets. Qualitative themes involved physical, economic, and social access to health facilities as well as issues of risk perception and self identity. The overall findings suggest that use of obstetric care is influenced by a complex interplay of factors closely tied to relative status in family and community. As individual agents differentially positioned by multiple markers of power, women pragmatically negotiate amidst a wide array of deterrents and motivators to secure the best care they can. In order to improve use of biomedical obstetric care, interventions aimed at increasing availability of these services should focus on improving access for women who are disadvantaged. PMID- 20579798 TI - Emotional valence and arousal effects on memory and hemispheric asymmetries. AB - This study examined predictions based upon the right hemisphere (RH) model, the valence-arousal model, and a recently proposed integrated model (Killgore & Yurgelun-Todd, 2007) of emotion processing by testing immediate recall and recognition memory for positive, negative, and neutral verbal stimuli among 35 right-handed women. Building upon methodologies of previous studies, we found that words presented to the right visual field/left hemisphere (RVF/LH) were recalled and recognized more accurately than words presented to the left visual field/right hemisphere (LVF/RH), and we found significant valence by visual field interactions. Some findings were consistent with one of the models evaluated whereas others were consistent with none of the models evaluated. Our findings suggest that an integration of the RH and valence-arousal models may best account for the findings with regard to hemispheric lateralization of memory for emotional stimuli. PMID- 20579799 TI - First trimester fasting hyperglycemia as a predictor for the development of gestational diabetes mellitus. AB - OBJECTIVE: Screening for gestational diabetes mellitus (GDM) is usually done at 24-28 weeks of gestation. Our goal was to study the association between first trimester fasting plasma glucose level and GDM risk and to evaluate its efficacy as a screening test for GDM in comparison to a traditional risk factor, pregestational body mass index (BMI). STUDY DESIGN: The charts of all patients who delivered in our hospital between June 2001 and June 2006 were reviewed. Only subjects with a singleton pregnancy and a recorded first trimester fasting glucose level and BMI were studied. Women with pregestational diabetes mellitus, fasting glucose level >105mg/dl or delivery at <24 weeks were excluded. Screening properties of both fasting glucose level and BMI were calculated and compared using receiver operator characteristic curves. RESULTS: GDM was diagnosed in 135 of the 4876 women included in this study. Fasting glucose cut-off levels of 80 85mg/dl yielded sensitivities of 75-55% and specificities of 52-75% for GDM prediction. BMI cut-off values of 25-28 had sensitivities of 60-40% and specificities of 72-86% for GDM prediction. Receiver operator curves for fasting glucose levels and BMI showed similar performance in predicting GDM (area under curve 0.72+/-0.023 vs. 0.74+/-0.021 (P=0.44)). There was approximately a 1.5-fold increase in the risk of developing GDM with each 5mg/dl increase in fasting glucose or 3.5kg/m2 increase in BMI. CONCLUSION: Higher first trimester fasting glucose levels, within the normoglycemic range, constitute an independent risk factor for the development of GDM among young pregnant women. PMID- 20579800 TI - Antenatal variables associated with severe adverse neurodevelopmental outcome among neonates born at less than 32 weeks. AB - OBJECTIVE: To determine the association between antenatal factors and severe adverse neurodevelopmental outcome (ANDO) in preterm infants. STUDY DESIGN: Neurodevelopmental follow-up was performed in a cohort of babies born at <32.0 weeks' gestation with birth weight <1500 grams between 1999 and 2006. Logistic regression analysis was used to relate obstetric, perinatal and neonatal ultrasonographic predictors to severe ANDO, defined as cerebral palsy or neurodevelopmental impairment, including sensory damage and adjusted development quotient <70. RESULTS: 88.6% (195/220) of surviving babies underwent follow up for a median of 24 months (range 12-96); 45 of them (23%) had ANDO, which was severe in 28 (14.3%). Abnormal ultrasonographic findings (intraventricular hemorrhage grades 3 or 4, periventricular leukomalacia, or ventriculomegaly) were observed in 18 cases (9.2%) and they were significantly associated with severe ANDO (OR 11.8 95% CI 4.0-34.0). Only gestational age at delivery (OR 0.80 95% CI 0.66-0.97), but not intrauterine infection, was independently related to severe ANDO. Infants with severe ANDO born before 28 weeks presented lower umbilical artery pH (7.24+/-0.1 vs 7.31+/-0.06, p=0.005) and a significantly higher rate of cesarean delivery (85.7% vs 50%, OR 6 95%CI 1.3-26.3, p=0.03) compared with infants without severe ANDO. CONCLUSION: Gestational age at delivery and low umbilical artery pH at less than 28 weeks, but not intrauterine infection, are independent risk factors for severe ANDO in babies with birth weight <1500g. PMID- 20579801 TI - Evaluation of preoperative lymphoscintigraphy and sentinel node procedure in vulvar cancer. AB - OBJECTIVE: To assess the value of preoperative lymphoscintigraphy, and to evaluate the validity and feasibility of the sentinel node (SN) procedure in vulvar carcinoma. STUDY DESIGN: Retrospective clinical and histopathological review of 77 patients with invasive squamous cell carcinoma in vulva who were treated at Karolinska University Hospital Stockholm, Sweden, from 2000 to 2007. The patients underwent SN mapping preoperatively with radioactive tracer and blue dye (n=60) or only blue dye (n=17). The SN was removed separately followed by complete inguinofemoral lymphadenectomy. RESULTS: The relation between SNs detected on the scintigram and those found during surgery showed good agreement using weighted kappa. The detection rate of SN was 98% for radioisotope plus blue dye, and 94% for blue dye alone. Two cases of false negative SN (false negative rate 2.7%) were found, both with large midline tumors. CONCLUSION: Preoperative scintigram is a valuable help to identify and localize the SNs and gives the best estimate of the accurate number but cannot determine if unilateral or bilateral groins should be explored in cases of midline tumors. Our results are in favor of using radioisotope and blue dye to identify the SNs. This study support previous reports that the method is not recommended for tumors larger than 40 mm to optimize detection of SN and minimize the false negative detection rate. PMID- 20579802 TI - Raman spectroscopy: a novel experimental approach to evaluating renal tumours. AB - BACKGROUND: New optical techniques of spectroscopy have shown promising results in the evaluation of solid tumours. OBJECTIVE: To evaluate the potential of Raman spectroscopy (RS) to assess renal tumours at surgery. DESIGN, SETTING, AND PARTICIPANTS: Over a 5-mo period, Raman optical spectra were prospectively acquired on surgical renal specimens removed due to suspicion of cancer. MEASUREMENTS: Raman measures were normalised to ensure comparison between spectra. A lower resolution signal was computed using a wavelet decomposition procedure to diminish the size of the signal and exploit the complete spectrum. A support vector machine (SVM) with a linear kernel and a sequential minimal optimisation solver was applied. A leave-one-out cross-validation technique was used to train and test the SVM. RESULTS AND LIMITATIONS: There were 36 patients with 34 malignant tumours (27 clear-cell, 6 papillary, and 1 chromophobe) and 2 benign (1 oncocytoma and 1 metanephric cyst) tumours. A total of 241 analysable Raman spectra were obtained. The SVM was able to classify tumoural and normal tissue with an accuracy of 84% (sensitivity 82%, specificity 87%). High-grade and low-grade tumours were differentiated with a precision of 82% (sensitivity 84%, specificity 80%). Histologic subtype could be categorised with an accuracy of 93% (sensitivity 96%, specificity 87%). SVM could not be applied to classify benign and malignant tumours because of the restricted number of benign spectra. CONCLUSIONS: RS can accurately differentiate normal and tumoural renal tissue, low-grade and high-grade renal tumours, and histologic subtype of renal cell carcinoma. Larger prospective studies are needed to confirm these preliminary data. PMID- 20579803 TI - Extracranial carotid artery disease in nasopharyngeal carcinoma patients with post-irradiation ischemic stroke. AB - OBJECTIVE: Irradiation induced extracranial carotid occlusive disease has been recognized as a potential cause of post-irradiation stroke in nasopharyngeal carcinoma (NPC) patients. Our study aims to investigate the prevalence of extracranial CA disease in post-irradiated Taiwanese NPC ischemic stroke patients. METHODS: Forty-three NPC patients with ischemic stroke were retrospectively selected from the stroke registration of the study hospital and compared with 276 first-ever ischemic stroke patients from the same database, of which 31 patients underwent carotid duplex sonography (CDS). Significant atherosclerotic lesions of the carotid arteries were defined as a >50% stenosis or an occlusion according to CDS. RESULTS: Significant carotid lesions occurred in 13 of 31 (42%) NPC patients. Stroke was more frequently caused by large artery disease (44% versus 23%; p<0.01) in NPC patients than in first-ever stroke patients without NPC. Carotid artery disease (odds ratio 7.22, 95% confidence interval 2.51-20.77; p<0.0001) and absence of diabetes mellitus (odds ratio 0.26, 95% confidence interval 0.07-0.93; p=0.039) were the strongest independent discriminators between NPC stroke patients and non-NPC stroke patients in a multivariate logistic regression analysis. CONCLUSION: Patients who received neck irradiation are at risk for the delayed development of diffused atherosclerosis but also for carotid occlusion within years, although the mechanism remains elusive and probably multifactorial. PMID- 20579804 TI - Recombinant high density lipoprotein reconstituted with apolipoprotein AI cysteine mutants as delivery vehicles for 10-hydroxycamptothecin. AB - 10-Hydroxycamptothecin (HCPT) is an effective anticancer agent whose therapeutic potential is limited by poor water-solubility and selectivity, short half-life and side effects. It has been shown that high density lipoprotein (HDL) or recombinant HDL (rHDL) reconstituted with wide-type apolipoprotein AI (apoAIwt) is an effective drug delivery model because of its specific structural characteristics and the targeted receptor-mediated uptake mechanism. In this study, the apoAI(Milano) (apoAI(M)) mutant with higher receptor affinity was chosen as a potential delivery vehicle from seven cysteine mutants of apoAI constructed by our laboratory. rHDL-HCPT nanoparticles reconstituted with apoAI(M), named as rHDL(M)-HCPT, seemed to be primarily spherical model with mean diameter were 22.39+/-10.25nm, which is similar with the diameter of natural HDL. rHDL(M)-HCPT showed a very steady sustained release pattern in vitro and increased the drug concentration in major organs, relative to free HCPT. Furthermore, in comparison with free HCPT, rHDL(M)-HCPT nanoparticles increased the cytotoxicity of HCPT by 70 and 50 times in SKOV-3 and HCT-116 cells. The data presented in this study indicate that rHDL(M) reconstituted with apoAI(M) could be exploited as a potential delivery vehicle of HCPT with controlled release, enhanced tissue distribution and higher cytotoxicity. PMID- 20579805 TI - Hunting for robust gene signature from cancer profiling data: sources of variability, different interpretations, and recent methodological developments. AB - Gene microarray is a powerful platform to investigate the expression patterns of thousands of genes simultaneously. One central objective of such analysis is to select sets of genes (i.e., gene signatures) which correlate with clinical characteristics, such as disease subtype diagnosis, response to drug treatment and prognosis. However, previous studies have found that mRNA signatures are highly unstable and strongly depend on the selection of patient samples. Based on five large microRNA profiling datasets, we empirically found that microRNA signatures are also generally unstable. Therefore, concerns arise regarding the reproducibility and clinical applicability of these derived gene signatures. Here, we first provide a brief review on the sources of variability and different interpretations of multiple distinct gene signatures. We then focus on those recent methodological progresses aimed at developing more stable gene signatures. PMID- 20579806 TI - Survivin mediates self-protection through ROS/cdc25c/CDK1 signaling pathway during tumor cell apoptosis induced by high fluence low-power laser irradiation. AB - Survivin, an important member of inhibitor-of-apoptosis (IAP) family, can be up regulated by various pro-apoptotic stimuli, such as UV, photodynamic therapy (PDT) and cisplatin. High fluence low-power laser irradiation (HF-LPLI) is a newly discovered pro-apoptotic stimulator. The anti-apoptotic mechanism of survivin during HF-LPLI-induced apoptosis is still not investigated. Here, we report that HF-LPLI up-regulates survivin activity through reactive oxygen species (ROS)/cdc25c protein phosphatase (cdc25c)/cyclin-dependent kinase (CDK1) signaling pathway in human lung adenocarcinoma cells (ASTC-a-1). The up regulation of survivin activity can reduce HF-LPLI-induced apoptosis, while down regulation of the activity can promote the apoptosis. In addition, activated survivin delays mitochondrial depolarization, cytochrome c release, caspase-9 and Bax activation, all of which are typical pro-apoptotic events of cell apoptosis induced by HF-LPLI. On the basis of the present studies, we conclude that survivin can mediate self-protection during tumor cell apoptosis caused by HF LPLI. PMID- 20579807 TI - Investigation of 4-year-old stabilised/solidified and accelerated carbonated contaminated soil. AB - The investigation of the pilot-scale application of two different stabilisation/solidification (S/S) techniques was carried out at a former fireworks and low explosives manufacturing site in SE England. Cores and granular samples were recovered from uncovered accelerated carbonated (ACT) and cement treated soils (S/S) after 4 years to evaluate field-performance with time. Samples were prepared for microstructural examination and leaching testing. The results indicated that the cement-treated soil was progressively carbonated over time, whereas the mineralogy of the carbonated soil remained essentially unchanged. Distinct microstructures were developed in the two soils. Although Pb, Zn and Cu leached less from the carbonated soil, these metals were adequately immobilised by both treatments. Geochemical modeling of pH-dependent leaching data suggested that the retention of trace metals resulted from different immobilisation mechanisms operating in the two soils examined. PMID- 20579808 TI - Removal of chromate and phosphate anion from aqueous solutions using calix[4]aren receptors containing proton switchable units. AB - In the present study four new calix[4]arene amide ionophores (4-7) have been prepared by aminolysis of calix[4]arene diester (3) and investigated their extraction ability toward phosphate and dichromate anions at different pH. The (1)H NMR data showed that the synthesized compounds exist in the cone conformation. Liquid-liquid extraction experiments have been performed to evaluate the dichromate and phosphate anions extraction efficiency of both calix[4]arene bearing amide-pyridinium units (4-7) and the calix[4]arene derivative bearing aminomethyl pyridinium units (8, 9). It was observed that, compounds 4-7 exhibited lower affinity toward phosphate ions than the calix[4]arene derivative bearing amine pyridinium units (8, 9). The extraction of phosphate and dichromate anions by these compounds indicates that the partially protonated pyridyl or amino groups play the major role for the formation of hydrogen bonds and electrostatic interactions. PMID- 20579809 TI - Solubilization of dibutyltin dichloride with surfactant solutions in single and mixed oil systems. AB - The harmful effects of organometallic compounds and their metabolites on the environment and human health require the development of more effective remediation methods. Surfactant enhanced remediation has been considered as a potential method for the removal of organometallic compounds; however, additional understanding is needed about the solubilization processes of these compounds. The surfactant enhanced solubilization of dibutyltin dichloride (DBT), an organometallic compound, was the focus of this research. In addition, the synergistic effects of DBT solubilization in perchloroethylene (PCE) and decane mixtures were evaluated. The results indicate that PCE and decane were solubilized into the core of these surfactant micelles in both single and mixed oil systems. DBT solubilization was limited when DBT alone was present (single oil system), and the nature of the solubilization isotherm suggests that DBT solubilization tended to occur near the micelle surface in a single oil system. DBT solubilization was found to increase when present in the PCE and decane oil mixture. PCE and decane may have facilitated the solubilization of DBT because they were solubilized in the micelle core. From this study, it may be concluded that the DBT behaves like polar oil such as dodecanol, having properties of a polar organic compound. PMID- 20579810 TI - Barium uptake by maize plants as affected by sewage sludge in a long-term field study. AB - A long-term experiment was carried out under field conditions in Jaboticabal, SP, Brazil, with the objective of evaluating the concentration of Ba in soil and in maize plants grown in a soil treated with sewage sludge for nine consecutive years. During 2005/2006, maize was used as test plants and the experimental design was in randomized complete blocks with four treatments and five replicates. Treatments consisted of: 0.0, 45.0, 90.0 and 127.5 t ha(-1) sewage sludge (dry basis). Sewage sludge application increased soil Ba concentration. Barium accumulated in the parts of maize plants were generally affected by the successive applications of sewage sludge to the soil. However, the concentration of Ba in maize grain did not exceed the critical levels of Ba for human consumption. Sewage sludge applied to soil for a long time did not affect dry matter and grain production, nevertheless had the similar effect of mineral fertilization. PMID- 20579811 TI - Sequential extraction and availability of copper in Cu fungicide-amended vineyard soils from Southern Brazil. AB - The continuous use of cupric fungicides in vineyards, mainly copper sulfate (as a component of the bordeaux mixture), has increased Cu concentration in soils to levels near or even above the maximum established by the Commission of Soil Chemistry and Fertility of the States of Santa Catarina and Rio Grande do Sul, Brazil. Besides the total content, the fractions of the element along the soil profile must be known, because the total content of Cu in the soil is not sufficient to express its environmental impact. The objective of this study was to evaluate the variation of Cu contentes along the soil profile and its speciation and partitioning in 29 soil samples from vineyards in the state of Rio Grande do Sul, Brazil. Samples were collected in areas cropped with vineyards older than 15 years that had been frequently treated with the bordeaux mixture. These samples were from Nitosols, Acrisols, Cambisols and Leptosols and were analysed by sequential extractions and several chemical extractors. Soils had diverse chemical and physical attributes: clay content in the plowed layer (0-0.2 m) ranged from 120 to 610 g kg(-1), pH ranged from 5.3 to 7.3 and organic carbon contents varied from 2.9 to 51 g dm(-3). Among the 29 samples, 16 had the total Cu above the maximum limit allowed by the European Community regulations (140 mg kg(-1)). The average amount of Cu bonded to the oxide fraction accounted for 49.5% of the total Cu. PMID- 20579812 TI - Subtypes of adolescent sedative/anxiolytic misusers: A latent profile analysis. AB - BACKGROUND: Few empirically-based taxonomies of nonmedical prescription drug misusers have been published. This study used latent profile analysis (LPA) to identify classes of adolescent sedative/anxiolytic misusers. METHODS: Interviews assessing substance use, psychiatric symptoms, antisocial traits/behavior, and traumatic life experiences were conducted with 723 Missouri youth in residential care for antisocial behavior. Sedative/anxiolytic misusers (N=247) averaged 15.8 (S.D.=1.1) years of age; a majority were male (83.8%), White (70.0%), and resided in rural/small town areas (53.8%). RESULTS: LPA yielded a three-class solution. Class 1 (59.1%) was comprised of youth with significantly lower levels of currently distressing psychiatric symptoms, fewer lifetime traumatic experiences, less problematic substance use histories, less frequent antisocial behavior, and less impulsivity than youth in Classes 2 and 3. Class 2 (11.3%) youth had high levels of currently distressing psychiatric symptoms and more frequent antisocial behavior compared to youth in Classes 1 and 3. Class 3 (29.5%) youth evidenced levels of psychiatric and behavioral problems that were intermediate to those of Class 1 and 2 youth. Frequency of sedative/anxiolytic misuse was significantly higher in Classes 2 and 3 compared to Class 1. Members of Class 2 and Class 3 also had the highest levels of psychiatric symptoms for which sedatives/anxiolytics are commonly prescribed. Significant differences between classes were observed across a range of health, mental health, personality, and behavioral variables. CONCLUSIONS: Adolescents who misused prescription sedatives/anxiolytics evidenced significant heterogeneity across measures of psychiatric and behavioral dysfunction. Youth with comparatively high levels of anxiety and depression reported significantly more intensive sedative/anxiolytic misuse than their counterparts and may be at high risk for sedative/anxiolytic abuse and dependence. PMID- 20579813 TI - Identification of suitable reference genes for gene expression analysis of pork meat quality and analysis of candidate genes associated with the trait drip loss. AB - The aim of this study was to identify a set of stably expressed endogenous control genes for quantitative PCR analysis of mRNA expression in the porcine LTL muscle and to subsequently perform expression analysis of potential candidate genes associated with drip loss. Expression stability of seven commonly used reference genes was examined in n=60 pigs from three independent populations of different genetic backgrounds. The genes examined were: ACTB, ATP5G1, B2M, GPX1, RPL4, TBP and YWHAZ. GeNorm analysis of expression stability identified B2M, RPL4 and TBP as consistently stable in each breed examined. Analysis of meat samples divergent for water holding capacity identified positive and negative associations between drip loss and gene expression using B2M, RPL4 and TBP as endogenous controls. Specifically, expression of COL1A1 increased significantly with increasing drip loss while expression of CAST decreased significantly with increasing drip loss. This study therefore indicates the use of B2M, RPL4 and TBP as suitable endogenous controls for gene expression analysis of the porcine LTL muscle. Further study is recommended to identify the detailed roles of COL1A1 and CAST with respect to the development of drip loss. PMID- 20579814 TI - Consumer perception and the role of science in the meat industry. AB - The relationship between consumer perception of quality and the food industry's drive to satisfy consumer needs is complex and involves many different components. Science and innovation play a major role in equipping the industry to respond to consumer concerns and expectations. This paper examines the main elements of consumer perception of meat with focus on the red meat sector. Emphasis is placed on perception at point of sale particularly the intrinsic quality cues of colour, packaging and degree of visual fat. The state of the art developments in increasing consumers' perception at this point are discussed. Experienced quality cues such as tenderness and flavour are well known as being of immense importance to consumers at point of consumption. The latest technological developments to enhance the quality experienced by consumers are discussed. The use of pre-rigor restraining techniques offers the industry a method for changing its conventional procedures of processing beef for instance. Background cues of safety, nutrition, animal welfare and sustainability are also discussed. Finally opportunities and challenges facing the industry are outlined. It is concluded that the meat industry needs to invest in and embrace an innovation agenda in order to be sustainable. It must utilise emerging scientific knowledge and take a more proactive role in setting out a research agenda. PMID- 20579815 TI - Consumer evaluation of venison sensory quality: effects of sex, body condition score and carcase suspension method. AB - Intact fallow bucks (n=20) and non-pregnant fallow does (n=24) (Dama dama), in the body condition score (BCS) of 2, 3 and 4 (lean, prime and fat) and rising 2 year old red deer stags (n=26) (Cervus elaphus) of the same BCS range (2-4) were used in this study to determine the impact of sex, BCS and method of carcase suspension on consumer perception of venison quality. Consumers were asked to evaluate cooked meat samples (M. gluteus medius) on an unstructured line scale for colour, flavour, tenderness, juiciness and overall liking. Meat from both fallow deer and red deer was preferred by consumers when carcases had hung by the pelvic suspension (PS) method compared with the Achilles tendon (AT) method of hanging (p<0.001). Consumers also noted a difference in colour between sexes in fallow deer venison, with venison from 36 month-old does being darker (p=0.015), and preferred venison from does over 18-24 month-old bucks. There was a significant difference in the consumer scores for tenderness in red deer stags of BCSs 2 and 4 (p=0.05) with panellists determining BCS 4 animals to be more tender; however no tenderness differences were observed for fallow deer does compared with bucks. PMID- 20579816 TI - Dose escalation for metastatic spinal cord compression in patients with relatively radioresistant tumors. AB - PURPOSE: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the "standard" regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. METHODS AND MATERIALS: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. RESULTS: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). CONCLUSIONS: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors. PMID- 20579817 TI - Prostate intrafraction motion assessed by simultaneous kilovoltage fluoroscopy at megavoltage delivery I: clinical observations and pattern analysis. AB - PURPOSE: To describe prostate intrafraction motion using kilovoltage fluoroscopy at treatment delivery for a hypofractionated radiotherapy protocol. METHODS AND MATERIALS: Kilovoltage images were acquired during treatment delivery, as well as pre- and posttreatment cone-beam computed tomography (CBCT) for each fraction of 30 patients, totaling 571 fractions for analysis. We calculated population statistics, evaluated correlation between interfraction and intrafraction motion, evaluated effect of treatment duration, classified whether motion resolved by posttreatment CBCT, and compared motion magnitude on a per-patient basis. RESULTS: The elapsed time between pre- and post-CBCTs was (18.6 +/- 4.5) min. The population mean of motion measured by kilovoltage fluoroscopy was (-0.1, 0.5, 0.6) mm, the systematic was (0.5, 1.3, 1.2) mm, and random was (0.9, 1.9, 2.0) mm in the right-left, anterior-posterior, and superior-inferior axes, respectively. The probability of motion increased with treatment duration, with the mean increasing to (0.0, 1.0, -0.9) mm and the systematic to (0.6, 1.7, 1.5) mm when measured using posttreatment CBCT. For any motion >=2 mm, approximately 75% did not resolve by posttreatment CBCT. Motion magnitude varied considerably among patients, with the probability of a 5-mm displacement ranging from 0.0% to 58.8%. CONCLUSIONS: Time dependency of intrafraction motion should be considered to avoid bias in margin assessment, with posttreatment CBCT slightly exaggerating the true motion. The patient-specific nature of the intrafraction motion suggests that a patient-specific management approach may be beneficial. PMID- 20579818 TI - A failure detection strategy for intrafraction prostate motion monitoring with on board imagers for fixed-gantry IMRT. AB - PURPOSE: To develop methods to monitor prostate intrafraction motion during fixed gantry intensity-modulated radiotherapy using MV treatment beam imaging together with minimal kV imaging for a failure detection strategy that ensures prompt detection when target displacement exceeds a preset threshold. METHODS AND MATERIALS: Real-time two-dimensional (2D) marker position in the MV image plane was obtained by analyzing cine-MV images. The marker's in-line movement, and thus its time-varying three-dimensional (3D) position, was estimated by combining the 2D projection data with a previously established correlative relationship between the directional components of prostate motion. A confirmation request for more accurate localization using MV-kV triangulation was triggered when the estimated prostate displacement based on the cine-MV data was greater than 3 mm. An interventional action alert followed on positive MV-kV confirmation. To demonstrate the feasibility and accuracy of the proposed method, simulation studies of conventional-fraction intensity-modulated radiotherapy sessions were done using 536 Calypso-measured prostate trajectories from 17 radiotherapy patients. RESULTS: A technique for intrafraction prostate motion management has been developed. The technique, using "freely available" cine-MV images and minimum on-board kV imaging (on average 2.5 images/fraction), successfully limited 3D prostate movement to within a range of 3 mm relative to the MV beam for 99.4% of the total treatment time. On average, only approximately one intervention/fraction was needed to achieve this level of accuracy. CONCLUSION: Instead of seeking to accurately and continuously localize the prostate target as existing motion tracking systems do, the present technique effectively uses cine MV data to provide a clinically valuable way to minimize kV usage, while maintaining high targeting accuracy. PMID- 20579819 TI - Alcohol consumption patterns in HIV-infected adults with alcohol problems. AB - OBJECTIVE: To understand patterns of alcohol consumption and baseline factors associated with favorable drinking patterns among HIV-infected patients. METHODS: We studied drinking patterns among HIV-infected patients with current or past alcohol problems. We assessed drinking status in 6-month intervals. Based on National Institute on Alcohol Abuse and Alcoholism guidelines a favorable drinking pattern was defined as not drinking risky amounts at each assessment or decreased drinking over time. All other patterns were defined as unfavorable. Logistic regression models were used to identify baseline factors associated with a favorable pattern. RESULTS: Among 358 subjects, 54% had a favorable drinking pattern with 44% not drinking risky amounts at every assessment, and 11% decreasing consumption over time. Of the 46% with an unfavorable pattern, 4% drank risky amounts each time, 5% increased, and 37% both decreased and increased consumption over time. Current alcohol dependence and recent marijuana use were negatively associated with a favorable pattern, while older age and female gender, and having a primary HIV risk factor of injection drug use were positively associated with a favorable pattern. CONCLUSION: Many HIV-infected adults with alcohol problems have favorable drinking patterns over time, and alcohol consumption patterns are not necessarily constant. Identifying HIV infected adults with a pattern of risky drinking may require repeated assessments of alcohol consumption. PMID- 20579820 TI - Erythrocyte binding preference of 16 subtypes of low pathogenic avian influenza and 2009 pandemic influenza A (H1N1) viruses. AB - All 16 subtypes of avian influenza viruses of low pathogenicity (LPAIV) as well as their hemagglutinin (H) antigens, and four 2009 pandemic influenza A (H1N1) virus isolates were assayed for hemagglutinating activity against 5 erythrocyte species: goose, guinea pig, human group O, chicken and horse. Of all viruses and antigens assayed, the highest hemagglutination (HA) titers were obtained with goose and guinea pig erythrocytes. Hemagglutinating activity of replicating LPAIV and LPAIV antigens decreased, in order, with chicken and human group O; meanwhile, horse erythrocytes yielded lowest or no HA titer. Moreover, the 2009 pandemic viruses did not agglutinate both horse and chicken erythrocytes. Our study concluded that goose and guinea pig erythrocytes are the best in HA assay for all subtypes of influenza viruses. PMID- 20579822 TI - Breast cancer, stem cells and sex hormones: part 1. The impact of fetal life and infancy. AB - Like other organs, the breast contains rare somatic stem cells (SCs) that are long-lived and slowly dividing. In the adult breast, they are closely regulated in areas located along the breast ducts called SC niches. Breast SCs can produce offspring that become ductal, alveoli or myoepithelial cells. In fetal life, SCs form the primitive breast ducts and up to 30 weeks of gestational age, this process appears to be largely independent of estrogen. Early life risk factors for breast cancer include birth weight, rapid growth during infancy and diet. The impact of these risk factors may be mediated through SC number. These somatic breast SCs persist into adult life and so they are exposed to oncogenic influences for much longer than the short-lived differentiated breast ductal and alveolar cells. As such, it is likely that the breast SC is a prominent target for carcinogenesis and so SC number may be an important determinant of breast cancer risk later in life. PMID- 20579821 TI - Detection and evaluation of novel herpesviruses in routine and pathological samples from Asian and African elephants: identification of two new probosciviruses (EEHV5 and EEHV6) and two new gammaherpesviruses (EGHV3B and EGHV5). AB - Systemic infections with elephant endotheliotropic herpesviruses (EEHV) cause a rapid onset acute hemorrhagic disease with an 85% mortality rate. More than 60 cases have been confirmed worldwide occurring predominantly in juvenile Asian elephants. Originally, three virus types EEHV1A, EEHV1B and EEHV2 were identified, all members of the Proboscivirus genus within the Betaherpesvirinae. However, four elephant gammaherpesviruses (EGHV) have also been found by DNA PCR approaches in eye and genital secretions of asymptomatic animals, and two more versions of the probosciviruses, EEHV3 and EEHV4, were recently detected in acute hemorrhagic disease cases. To ask whether even more species of elephant herpesviruses may exist, we have developed several new diagnostic DNA PCR assays using multiple round primers in the DNA POL region. These have been used routinely for nearly three years to screen samples submitted to the Elephant Herpesvirus Laboratory for diagnosis of possible cases of EEHV disease in blood and necropsy tissue, as well as in biopsies of other suspicious lesions or growths. Several more cases of EEHV1-associated hemorrhagic disease were confirmed, but in addition, we describe here eleven examples of other known and novel herpesviruses detected and evaluated with these reagents. They include the prototypes of four new elephant herpesviruses, two more within the proboscivirus group EEHV5 and EEHV6, plus two more gammaherpesviruses EGHV3B and EGHV5. We also report initial semi-quantitative PCR assays demonstrating very high viral loads in the blood of the EEHV3 and EEHV4-associated hemorrhagic disease cases. PMID- 20579823 TI - External auditory canal stenting utilizing a useful rolled, tapered silastic sheet (RTSS) post middle ear surgery. AB - OBJECTIVE: To overcome the demerits of conventional postoperative aural packing, we developed a useful protocol for postoperative stenting of the external auditory canal after middle ear surgery which enables transcanal drainage and simultaneously allows for visual inspection and treatment of the canal, as necessary. METHODS: Twenty-four surgeries, 21 patients underwent tympanoplasty with a postaural incision. At the end of all surgical procedures, the external auditory canal was packed with a 0.3mm thickness rolled, tapered silastic sheet (RTSS) with antibiotic ointment applied to one surface. The inserted RTSSs were removed at 5-10 days postoperatively. We assessed the efficacy and the reliability of the RTSS. RESULTS: In 23 ear surgeries on 20 patients, we achieved successful postoperative ear packing utilizing our RTSS. With these patients, the tympanic membrane and the external auditory meatus were able to be observed immediately after the completion of the stenting during the surgery and the removal of the gauze over the operated ear at Day 1 to Day 3 postoperatively. During 4 surgeries with ventilation tube insertion to the tympanic membrane, there was secretion through the inserted ventilation tube which was easy to suction. In one surgery, on one patient, additional packing materials were utilized once only during a sandwich graft myringoplasty. No patients showed any harmful effects during the postoperative period. CONCLUSIONS: The useful and reliable RTSS, with antibiotic ointment applied to one surface, has several positive advantages that the conventional packing methods do not. PMID- 20579824 TI - [Superficial venous thrombosis of the penis: penile Mondor's disease? A case report and literature review]. AB - Mondor's disease is a rare cause of superficial thrombophlebitis, which is very exceptionally observed in the penis. Usually a benign condition, careful etiological search is needed to avoid missing exceptional causes. Mondor's disease is generally treated with non-steroidal anti-inflammatory drugs or low molecular-weight heparin and resolves without sequelae. Mondor's disease and superficial venous thrombosis of the penis may or may not be a unique clinical entity. A favorable outcome with no precise etiology would favor penile Mondor's disease. PMID- 20579825 TI - [A complicated infectious aortitis]. PMID- 20579826 TI - The place of endoscopic ultrasound in bilio-pancreatic pathology. AB - The place of endoscopic ultrasound (EUS) in malignant pathology of the pancreas is two-fold: (1) EUS is the best examination for the diagnosis of small tumours (<3cm in diameter). Its sensitivity is greater than that of CT scan, percutaneous ultrasound or magnetic resonance imaging (MRI) and is equal to that of endoscopic retrograde cholangiopancreatography (ERCP) without sharing its invasive character; (2) EUS is also indicated in the assessment of locoregional extension of tumours judged resectable by tomodensitometric (TDM) (scanner) data. The performance of EUS seems to be greater than other imaging techniques for the diagnosis of vascular and lymph node invasion although recent studies report less good results than those of studies in 1992 to 1994, particularly for vascular involvement. Nevertheless, EUS cannot affirm the malignant or benign character of these pancreatic masses. The development over the last 20 years of linear sector based EUS has enabled us to perform guided biopsies of such lesions. EUS-guided biopsy is today the best technique for obtaining the histology of a pancreatic mass, with a sensitivity of 85 to 87%. Furthermore, it also has a non-negligible impact on the deciding the treatment particularly in the case of adenocarcinomas (ADKP) not visible to TDM (scanners). This is currently of importance because trials are being developed of preoperative radio-chemotherapy for resectable lesions. probably in the next future, contrast-enhanced EUS (CE-EUS) and elastography will improve the results of EUS and will be necessary for a precise local staging before treatment. PMID- 20579827 TI - Superior mesenteric artery syndrome: a rare etiology of upper intestinal obstruction in adults. AB - The superior mesenteric artery (SMA) syndrome is an atypical cause of high intestinal obstruction in adults. Formerly considered controversial, this syndrome has now been recognized as a real clinical entity which results from extrinsic compression of the third portion of the duodenum by reduction of the angle formed between the SMA and the aorta, usually favoured by rapid and dramatic weight loss. We report a case observed in a 25-year-old female. The abdominal scan provided the diagnosis. Laparoscopic duodenojejunostomy provided cure after failure of initial conservative treatment. PMID- 20579828 TI - Capability of abdominal 320-detector row CT for small vasculature assessment compared with that of 64-detector row CT. AB - OBJECTIVE: To compare the capability of 320-detector row CT (area-detector CT: ADCT) with step-and-shoot scan protocol for small abdominal vasculature assessment with that of 64-detector row CT with helical scan protocol. MATERIALS AND METHODS: Total of 60 patients underwent contrast-enhanced abdominal CT for preoperative assessment. Of all, 30 suspected to have lung cancer underwent ADCT using step-and-shoot scan protocol. The other 30 suspected to have renal cell carcinoma underwent 64-MDCT using helical scan protocol. Two experienced radiologists independently assessed inferior epigastric, hepatic subsegmental (in the segment 8), mesenteric marginal (Griffith point) and inferior phrenic arteries by using 5-point visual scoring systems. Kappa analysis was used for evaluation of interobserver agreement. To compare the visualization capability of the two systems, the Mann-Whitney U-test was used to compare the scores for each of the arteries. RESULTS: Overall interobserver agreements for both systems were almost perfect (kappa>0.80). Visualization scores for inferior epigastric and mesenteric arteries were significantly higher for ADCT than for 64-detector row CT (p<0.05). No significant difference was found for hepatic subsegmental and inferior phrenic arteries. CONCLUSION: Small abdominal vasculature assessment by ADCT with step-and-shoot scan protocol is potentially equal to or better than that by 64-detector row CT with helical scan protocol. PMID- 20579829 TI - Integration of EEG source imaging and fMRI during continuous viewing of natural movies. AB - Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are noninvasive neuroimaging tools which can be used to measure brain activity with excellent temporal and spatial resolution, respectively. By combining the neural and hemodynamic recordings from these modalities, we can gain better insight into how and where the brain processes complex stimuli, which may be especially useful in patients with different neural diseases. However, due to their vastly different spatial and temporal resolutions, the integration of EEG and fMRI recordings is not always straightforward. One fundamental obstacle has been that paradigms used for EEG experiments usually rely on event-related paradigms, while fMRI is not limited in this regard. Therefore, here we ask whether one can reliably localize stimulus-driven EEG activity using the continuously varying feature intensities occurring in natural movie stimuli presented over relatively long periods of time. Specifically, we asked whether stimulus-driven aspects in the EEG signal would be co-localized with the corresponding stimulus-driven BOLD signal during free viewing of a movie. Secondly, we wanted to integrate the EEG signal directly with the BOLD signal, by estimating the underlying impulse response function (IRF) that relates the BOLD signal to the underlying current density in the primary visual area (V1). We made sequential fMRI and 64-channel EEG recordings in seven subjects who passively watched 2-min-long segments of a James Bond movie. To analyze EEG data in this natural setting, we developed a method based on independent component analysis (ICA) to reject EEG artifacts due to blinks, subject movement, etc., in a way unbiased by human judgment. We then calculated the EEG source strength of this artifact-free data at each time point of the movie within the entire brain volume using low-resolution electromagnetic tomography (LORETA). This provided for every voxel in the brain (i.e., in 3D space) an estimate of the current density at every time point. We then carried out a correlation between the time series of visual contrast changes in the movie with that of EEG voxels. We found the most significant correlations in visual area V1, just as seen in previous fMRI studies (Bartels A, Zeki, S, Logothetis NK. Natural vision reveals regional specialization to local motion and to contrast-invariant, global flow in the human brain. Cereb Cortex 2008;18(3):705 717), but on the time scale of milliseconds rather than of seconds. To obtain an estimate of how the EEG signal relates to the BOLD signal, we calculated the IRF between the BOLD signal and the estimated current density in area V1. We found that this IRF was very similar to that observed using combined intracortical recordings and fMRI experiments in nonhuman primates. Taken together, these findings open a new approach to noninvasive mapping of the brain. It allows, firstly, the localization of feature-selective brain areas during natural viewing conditions with the temporal resolution of EEG. Secondly, it provides a tool to assess EEG/BOLD transfer functions during processing of more natural stimuli. This is especially useful in combined EEG/fMRI experiments, where one can now potentially study neural-hemodynamic relationships across the whole brain volume in a noninvasive manner. PMID- 20579830 TI - Characterization of interaction and the effect of carbamazepine on the structure of human serum albumin. AB - The binding of carbamazepine (CBZ) to human serum albumin (HSA) was investigated under simulative physiological conditions. In this study, intrinsic fluorescence of tryptophan-214 in HSA was monitored upon the addition of CBZ. Binding constant of CBZ-HSA was calculated by the remarkable static quenching effect of CBZ and found to be (2.081+/-0.023)x10(4)M(-1). The fluorimetric results revealed that the hydrophobic interaction was a predominant intermolecular force for stabilizing the complex, which is also in agreement with the results obtained from voltammetric approach. Three site probes, warfarin, ibuprofen and digitoxin, were employed in fluorescence displacement experiments to locate the exact binding site for CBZ in HSA. The alteration in secondary structure of protein in the presence of CBZ was confirmed by the evidences from circular dichroism and FT IR spectroscopy. Further, the distance r between donor (Trp-214) and acceptor (CBZ) was obtained according to fluorescence resonance energy transfer (FRET). PMID- 20579832 TI - Self-investigation in adolescent chronic fatigue syndrome: narrative changes and health improvement. AB - OBJECTIVE: A small-scale intervention study into narrative self-investigation in adolescent chronic fatigue syndrome (CFS). METHOD: The self-confrontation method (SCM) is an instrument to assess and change personal life stories. Forty-two adolescents diagnosed with CFS were included and randomly assigned to either 6 or 12 sessions with the SCM. Twenty-five healthy adolescents were assigned to 6 sessions. Outcome was measured directly after the self-investigation procedure at 4 months. Follow-up measurements were made 10 months later. The Checklist Individual Strength and the Child Health Questionnaire were used to measure changes in fatigue, physical and psychosocial functioning. RESULTS: Self investigation resulted in significant changes in participants' narratives. Moreover, after self-investigation there was a significant improvement in fatigue, physical and psychosocial functioning for the adolescents with CFS. The patients who completed 12 sessions improved most. At follow-up, the positive effects were maintained. CONCLUSION: Self-investigation enables a move beyond the symptoms of CFS in an individualized, patient centered way. Narrative transformation seems to contribute to improved physical and psychosocial outcome in adolescent CFS. PRACTICE IMPLICATIONS: The SCM allows adolescents to discover (for themselves) factors that might cause or perpetuate their fatigue. The results suggest that self-investigation is a useful instrument in the management of adolescent CFS. PMID- 20579833 TI - Pain in ehlers-danlos syndrome is common, severe, and associated with functional impairment. AB - CONTEXT: The Ehlers-Danlos Syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Musculoskeletal pain is mentioned in the diagnostic criteria and described as early in onset, chronic, and debilitating. However, systematic research on pain in EDS is scarce. OBJECTIVES: We investigated prevalence and impact of pain and associated features in a large group of EDS patients. METHODS: We performed a study among members of the Dutch EDS patient organization (n=273) and included the McGill Pain Questionnaire to investigate various aspects of pain, the Sickness Impact Profile to study functional impairment, the Symptom Checklist subscale sleep to evaluate sleep disturbances, and the Checklist Individual Strength subscale fatigue to determine fatigue severity. RESULTS: The results of this study show that 1) chronic pain in EDS is highly prevalent and associated with regular use of analgesics; 2) pain is more prevalent and more severe in the hypermobility type than in the classic type; 3) pain severity is correlated with hypermobility, dislocations, and previous surgery; 4) pain is correlated with low nocturnal sleep quality; and 5) pain contributes to functional impairment in daily life, independent of the level of fatigue. CONCLUSION: From this large cohort of EDS patients, we conclude that pain is common and severe in EDS. Pain is related to hypermobility, dislocations, and previous surgery and associated with moderate to severe impairment in daily functioning. Therefore, treatment of pain should be a prominent aspect of symptomatic management of EDS. PMID- 20579834 TI - An analysis of heavy utilizers of opioids for chronic noncancer pain in the TROUP study. AB - CONTEXT: Although opioids are increasingly used for chronic noncancer pain (CNCP), we know little about opioid dosing patterns among individuals with CNCP in usual care settings, and how these are changing over time. OBJECTIVES: To investigate the distribution of mean daily dose and mean days supply among patients with CNCP in two disparate populations, one national and commercially insured population (HealthCore) and one state based and publicly insured (Arkansas Medicaid), for years 2000 and 2005. METHODS: For individuals with any opioid use, we calculated the distribution of mean daily dose (in milligram morphine equivalents), mean days supply in a year, mean annual dose, and patient characteristics associated with heavy utilizers of opioids. RESULTS: Between 2000 and 2005, across all percentiles, there was little change in the mean daily opioid dose. In HealthCore, mean days supply increased most rapidly at the top end of the days supply distribution, whereas in Arkansas Medicaid, the greatest increases were near the median of days supply. In HealthCore, the top 5% of users accounted for 70% of total use (measured in milligram morphine equivalents), and the top 5% of Arkansas Medicaid users accounted for 48% of total use. The likelihood of heavy opioid utilization was increased among individuals with multiple pain conditions, and in HealthCore, among those with mental health and substance use disorders. CONCLUSION: Opioid use is heavily concentrated among a small percent of patients. The characteristics of these high utilizers need to be further established, and the benefits and risks of their treatment evaluated. PMID- 20579835 TI - Does recall period have an effect on cancer patients' ratings of the severity of multiple symptoms? AB - CONTEXT: Choosing an appropriate recall period for symptom assessment in a clinical trial is dependent on the design and purpose of the trial. OBJECTIVE: To examine the effects of recall on symptom severity ratings by comparing ratings made using 24-hour and seven-day recall periods of the MD Anderson Symptom Inventory (MDASI). METHODS: Forty-two patients in their third to eighth week of chemoradiation rated their symptoms using the MDASI on two separate occasions (T1 and T2), one week apart. At T1, patients were randomly assigned to rate symptoms using either a 24-hour or a seven-day recall. At T2, patients rated symptoms using the recall period not used at their first visit. RESULTS: Comparing the 24 hour and seven-day recall periods, the correlation coefficient for total symptom severity was 0.888. All correlation coefficients for symptom severity items were >0.7 except for distress (r=0.67). The percentages of moderate to severe symptoms (rated >or=5) were consistent for both recall periods, with no significant difference between recall periods in the prevalence of moderate to severe symptoms. Cronbach alpha coefficients for both 24-hour and seven-day recalls were >0.8. Symptoms from both recall periods were more severe for patients with poorer performance status. Twenty patients were cognitively debriefed; 70% thought that the seven-day recall was "more appropriate" for the MDASI, but 85% did not think that recall period would influence their answers. CONCLUSION: This study demonstrated that the MDASI in a seven-day recall format has psychometric properties consistent with the 24-hour recall version, which may promote its use in future cancer clinical trials and may inform the choice of recall period when symptoms are outcome measures. PMID- 20579836 TI - Sources of emotional distress associated with diarrhea among late middle-age and older HIV-infected adults. AB - CONTEXT: Although the experience of physical symptoms can adversely influence emotional well-being, the specific emotional reactions experienced in response to specific symptoms are not well understood. OBJECTIVES: To examine the emotional impact of diarrhea among HIV+ late middle-age and older adults (i.e., age 50 years and older). METHODS: In-depth interviews were conducted with 100 participants, of whom 29 had experienced diarrhea and spoke about the emotional impact it had had on them. RESULTS: Three principal themes emerged: 1) I don't control the diarrhea, the diarrhea controls me; 2) I feel ashamed, dirty, and tainted; and 3) I fear what the diarrhea is doing to me and what it means. Their inability to control when and where their diarrhea would occur was a great source of emotional distress for participants. Almost all feared the possibility of fecal incontinence while out in public and the humiliation it would bring. To avoid this, many greatly restricted their time outside the home or where they would go to ensure access to a restroom. Others felt shame and perpetually "dirty" even when not dealing with a bout of diarrhea. Many also worried about the effect the diarrhea would have on their health and whether it signaled progression to end-stage disease. CONCLUSION: The data strongly support the need to aggressively manage diarrhea in HIV-infected adults, as the social and emotional consequences can be profound. When it cannot be effectively controlled, physicians and social service agencies should address the isolation by providing home-based opportunities for social support and interaction. PMID- 20579837 TI - An exploratory study on the effects of an expectancy manipulation on chemotherapy related nausea. AB - CONTEXT: Previous research has shown that the effectiveness of acupressure bands in reducing chemotherapy-related nausea is related to patients' expectations of efficacy. OBJECTIVE: To test whether an informational manipulation designed to increase expectation of efficacy regarding acupressure bands would enhance their effectiveness. METHODS: We conducted an exploratory, four-arm, randomized clinical trial in breast cancer patients about to begin chemotherapy. All patients received acupressure bands and a relaxation CD. This report focuses on Arm 1(expectancy-neutral informational handout and CD) compared with Arm 4 (expectancy-enhancing handout and CD). Randomization was stratified according to the patient's level of certainty that she would have treatment-induced nausea (two levels: high and low). Experience of nausea and use of antiemetics were assessed with a five-day diary. RESULTS: Our expectancy-enhancing manipulation resulted in improved control of nausea in the 26 patients with high nausea expectancies but lessened control of nausea in 27 patients having low nausea expectancies. This interaction effect (between expected nausea and intervention effectiveness) approached statistical significance for our analysis of average nausea (P=0.084) and reached statistical significance for our analysis of peak nausea (P=0.030). Patients receiving the expectancy-enhancing manipulation took fewer antiemetic pills outside the clinic (mean(enhanced)=12.6; mean(neutral)=18.5, P=0.003). CONCLUSION: This exploratory intervention reduced antiemetic use overall and also reduced nausea in patients who had high levels of expected nausea. Interestingly, it increased nausea in patients who had low expectancies for nausea. Confirmatory research is warranted. PMID- 20579838 TI - The costs of treating terminal patients. AB - CONTEXT: In addition to the effectiveness of terminal care, policy makers and health care payers are concerned about the costs of treating terminal patients in a context of spiraling health care costs and limited resources. OBJECTIVES: This article aims to review the international literature on the costs of treating terminal patients. METHODS: Studies were identified by searching PubMed, Centre for Reviews and Dissemination databases, Cochrane Database, and EconLit, up to April 2009. Studies were included that contrasted costs in different health care settings and that compared palliative care with alternative therapeutic approaches for terminal patients. RESULTS: The few studies that focused on treatment of terminal patients across health care settings showed that hospitalization costs represent the principal component of palliative care costs. In the hospital setting, palliative care tends to be cheaper than usual care or care delivered in units other than the palliative care unit. Palliative care costs depend on patient characteristics, such as diagnosis, status of disease, and age. Also, different care models appear to target different patient groups and offer varied packages of services. Finally, there is some evidence pointing to cost advantages of palliative care at home as compared with alternative care models, although this needs to be corroborated by further research. CONCLUSION: Different approaches to deliver palliative care are not substitutes of each other and, thus, have different costs. From a cost perspective, hospitals need to pay attention to admitting patients to the palliative care unit at the right time. PMID- 20579839 TI - Validation of the Patient Care Monitor (Version 2.0): a review of system assessment instrument for cancer patients. AB - CONTEXT: The Patient Care Monitor (PCM) is a review of systems survey delivered by means of an electronic patient-reported outcomes (ePRO) data capture system that uses wireless tablet computers. Although the PCM 1.0 is validated, the updated PCM 2.0 has not been validated nor tested in the academic setting. OBJECTIVES: To validate and test the PCM 2.0 in three cancer populations. METHODS: Two hundred seventy-five individuals participated in three clinical trials enrolling breast (n=65), gastrointestinal (n=113), and lung (n=97) cancer patients. Internal consistency was evaluated using Cronbach's alpha coefficients calculated for six PCM subscales (general physical symptoms, treatment side effects, distress, despair, impaired performance, and impaired ambulation) and a Quality-of-Life Index. Construct validity was evaluated through Pearson's correlation between PCM subscales and subscales of the Functional Assessment of Cancer Therapy--General (FACT-G), the M.D. Anderson Symptom Inventory (MDASI), and the Functional Assessment of Chronic Illness Therapy--Fatigue (FACIT-F). The participants had the following characteristics: mean age was 58 years (standard deviation: 11), 52% were females, 79% were whites, 17% were blacks, 62% had no college degree, and 78% had metastatic or recurrent disease. RESULTS: Raw and normalized scores for PCM 2.0 subscales were internally consistent across study cohorts. PCM 2.0 subscales correlated significantly (P<0.05) with the corresponding subscales on FACT-G, MDASI, and FACIT-F, with the exception of FACT G social well-being, particularly for the lung cancer population. These correlations demonstrated construct validity. PCM 2.0 results followed expected patterns by cancer etiology. Prior reports demonstrate patient satisfaction with PCM 2.0. CONCLUSION: Within three unique academic oncology populations, PCM 2.0 is a valid ePRO instrument for assessing symptoms with seven patient-centered subscale or index domains. PMID- 20579841 TI - Biomechanics of the cricoarytenoid joint: three-dimensional imaging and vector analysis. AB - OBJECTIVES/HYPOTHESIS: Laryngeal framework surgery requires a good understanding of the biomechanics of the cricoarytenoid (CA) joint, the precise function of which is still only poorly understood. The aim of the study was (1) to show that, by superimposing two or more three-dimensional (3D) images, we can visualize the exact position of the arytenoid cartilages within the larynx at different phases of their movement; and (2) to demonstrate that it is possible to analyze the arytenoid cartilage movements mathematically with the help of vector analysis. STUDY DESIGN: In vitro cadaver study. METHODS: Twenty fresh and intact cadaver larynges were scanned by high-resolution computerized tomography with the arytenoid cartilages in "respiratory" position and in "phonatory" position. The two positions were superimposed and rendered in 3D with MIMICS (Materialise Interactive Medical Image Control System, Leuven, Belgium). The spatial trajectory of the arytenoid cartilage movements was calculated with vector analysis. RESULTS: The movement from the "respiratory" to the "phonatory" position has three components: (1) an inward rocking action around the longitudinal CA joint; (2) a forward sliding movement along the longitudinal axis of the CA joint; and (3) an inward rotation around a virtual axis that runs perpendicular to the CA joint axis. CONCLUSIONS: Superimposing 3D images of the larynx with the help of the software package MIMICS allows us to visualize and to analyze mathematically the trajectory of the arytenoid cartilage. The arytenoid cartilages rock inward, slide forward, and rotate inward when they move from the "respiratory" to the "phonatory" position. PMID- 20579840 TI - Hope in the context of lung cancer: relationships of hope to symptoms and psychological distress. AB - CONTEXT: Hope may be important in explaining the variability in how patients adjust to lung cancer. OBJECTIVES: The aim of this study was to examine how hope, as conceptualized by Snyder et al., is associated with multiple indices of adjustment to lung cancer. This theoretical model of hope suggests that people with high levels of hope are able to think about the pathways to goals (pathways) and feel confident that they can pursue those pathways to reach their goals (agency). METHODS: We hypothesized that higher levels of hope, as measured by Snyder et al.'s hope scale, would be related to lower levels of pain and other lung cancer symptoms (i.e., fatigue and cough) and lower psychological distress (i.e., depression). Participants in this study included patients with a diagnosis of lung cancer (n=51). All participants provided demographic and medical information and completed measures of hope, lung cancer symptoms, and psychological distress. RESULTS: Data analyses found that hope was inversely associated with major symptoms of cancer (i.e., pain, fatigue, and cough) and psychological distress (i.e., depression), even after accounting for important demographic and medical variables (i.e., age and cancer stage). CONCLUSION: The findings of this cross-sectional study highlight the potential importance of hope in understanding adjustment to lung cancer. Future longitudinal research could help reveal how hope and adjustment interact over the course of cancer survivorship. PMID- 20579842 TI - Categorizing normal and pathological voices: automated and perceptual categorization. AB - OBJECTIVES: The aims of the present study were to evaluate the accuracy of an elaborated automated voice categorization system that classified voice signal samples into healthy and pathological classes and to compare it with classification accuracy that was attained by human experts. MATERIAL AND METHODS: We investigated the effectiveness of 10 different feature sets in the classification of voice recordings of the sustained phonation of the vowel sound /a/ into the healthy and two pathological voice classes, and proposed a new approach to building a sequential committee of support vector machines (SVMs) for the classification. By applying "genetic search" (a search technique used to find solutions to optimization problems), we determined the optimal values of hyper parameters of the committee and the feature sets that provided the best performance. Four experienced clinical voice specialists who evaluated the same voice recordings served as experts. The "gold standard" for classification was clinically and histologically proven diagnosis. RESULTS: A considerable improvement in the classification accuracy was obtained from the committee when compared with the single feature type-based classifiers. In the experimental investigations that were performed using 444 voice recordings coming from 148 subjects, three recordings from each subject, we obtained the correct classification rate (CCR) of over 92% when classifying into the healthy pathological voice classes, and over 90% when classifying into three classes (healthy voice and two nodular or diffuse lesion voice classes). The CCR obtained from human experts was about 74% and 60%, respectively. CONCLUSION: When operating under the same experimental conditions, the automated voice discrimination technique based on sequential committee of SVM was considerably more effective than the human experts. PMID- 20579843 TI - Expectations, validity, and reality in gene expression profiling. AB - OBJECTIVE: To provide a critical overview of gene expression profiling methodology and discuss areas of future development. RESULTS: Gene expression profiling has been used extensively in biological research and has resulted in significant advances in the understanding of the molecular mechanisms of complex disorders, including cancer, heart disease, and metabolic disorders. However, translating this technology into genomic medicine for use in diagnosis and prognosis faces many challenges. In addition, gene expression profile analysis is frequently controversial, because its conclusions often lack reproducibility and claims of effective dissemination into translational medicine have, in some cases, been remarkably unjustified. In the last decade, a large number of methodological and technical solutions have been offered to overcome the challenges. STUDY DESIGN AND SETTING: We consider the strengths, limitations, and appropriate applications of gene expression profiling techniques, with particular reference to the clinical relevance. CONCLUSION: Some studies have demonstrated the ability and clinical utility of gene expression profiling for use as diagnostic, prognostic, and predictive molecular markers. The challenges of gene expression profiling lie with the standardization of analytic approaches and the evaluation of the clinical merit in broader heterogeneous populations by prospective clinical trials. PMID- 20579845 TI - Nutritional support in head injury. AB - Nutritional support is imperative to the recovery of head-injury patients. Hypermetabolism and hypercatabolism place this patient population at increased risk for weight loss, muscle wasting, and malnutrition. Nutrition management may be further complicated by alterations in gastrointestinal motility. Resting energy expenditure should be measured using indirect calorimetry and protein status measured using urine urea nitrogen. Providing early enteral nutrition within 72 hours of injury may decrease infection rates and overall complications. Establishing standards of practice and nutrition protocols will assure patients receive optimal nutrition assessment and intervention in a timely manner. PMID- 20579844 TI - B-cell delivered gene therapy for tolerance induction: role of autoantigen specific B cells. AB - Antigen-specific tolerance induction using autologous B-cell gene therapy is a potential treatment to eliminate undesirable immune responses. For example, we have shown that experimental autoimmune encephalomyelitis (EAE) and type 1 diabetes in NOD mice can be ameliorated using antigen-Ig fusion protein transduced B cells. However, it is well established that auto-reactive antigen specific B cells are activated in many autoimmune diseases and can contribute to pathogenesis. While syngeneic B cells from immunized or autoimmune mice can serve as tolerogenic antigen-presenting cells (APC), this observation begs the question of whether the antigen-specific B cells per se can be transduced as tolerogenic APC. To test this, we employed two model systems employing B cell receptor (BCR) transgenic or wild type (wt) mice as B-cell donors. While adoptively transferred MOG-Ig transduced wt C57Bl/6 B cells were highly tolerogenic and ameliorated EAE, MOG-Ig transduced anti-MOG B cells from BCR transgenic mice were not. This phenomenon was reproduced in the NOD diabetes model in which pro-insulin-Ig transduced polyclonal wt NOD B cells were protective, whereas similarly transduced anti-insulin BCR B cells were not. Since the frequency of antigen specific B cells in an immunized animal is quite low, we wished to determine the threshold numbers of BCR transgenic B cells that could be present in an effective transduced population. Therefore, we "spiked" polyclonal wt C57Bl/6 B cells with different numbers of anti-MOG BCR transgenic B cells. In the EAE model, we found protection when BCR B cells were present at 1%, but they prevented tolerance induction at 10%. Antigen-specific B cells expressed normal levels of co stimulatory molecules and were tolerogenic when transduced with an irrelevant antigen (OVA). Thus, the presence of a BCR specific for the target autoantigen may interfere with the tolerogenic process to that antigen, but BCR-specific B cells are not intrinsically defective as tolerogenic APC. Taken together, these data suggest that antigen-specific tolerance induction can be achieved in the presence of a limited number of antigen-specific B cells, but higher numbers of pathogenic B cells may mask this induction. This observation should guide future development of therapies using autologous B cells to treat patients with autoimmune diseases. PMID- 20579846 TI - Energy-drink consumption in college students and associated factors. AB - OBJECTIVE: To investigate the frequency of energy-drink consumption and associated factors in a group of college students. METHODS: A cross-sectional study was conducted in Hacettepe University (Ankara, Turkey) and included 439 students pursuing a career in medicine, sports, and arts. Only fourth-year students were approached. Data were collected using a self-administered standard questionnaire. RESULTS: In bivariate analyses, frequency of energy-drink consumption was higher in students of arts and sports and in those who did not have breakfast on a regular basis, ever smoked cigarettes, drank alcoholic beverages, and regularly engaged in sports compared with their counterparts. Many students who had "ever" tried an energy drink did so the first time because they wondered about its taste. Of regular users of energy drinks, reasons for using such drinks varied across the three selected groups of students and included obtaining getting energy, staying awake, boosting performance while doing sports, or mixing with alcoholic beverages. About 40% of all current users of energy drinks reported that they mixed those with alcoholic beverages. In multivariate analyses, statistically significant predictors of energy-drink consumption were faculty type, presence of any health insurance, use of alcoholic beverages, and monthly income, controlling for gender. Most students could not correctly define the ingredients of energy drinks or their potential hazardous health effects, and they could not distinguish energy and sports drinks when they were requested to select them from a list of commercial names of various drinks. CONCLUSION: Consumption of energy drinks, despite the variation in the reason for choosing such drinks, is quite common in college students. Awareness of university students of the ingredients and potential health hazards of energy drinks, in particular in mixing with alcoholic beverages, should be increased. PMID- 20579847 TI - Beneficial effects of fructo-oligosaccharides supplementation on fecal bifidobacteria and index of peroxidation status in constipated nursing-home residents--a placebo-controlled, diet-controlled trial. AB - OBJECTIVE: This study assessed effects of fructo-oligosaccharides (FOS) supplementation on fecal bifidobacteria, lipid peroxidation index, indices of nutritional status, and whether effects of FOS were sustained after its withdrawal in constipated nursing-home residents. The associations of fecal bifidobacteria and blood measurements were also examined. METHODS: Six men and four women participated in a double-blind, diet-controlled study that consisted of a 4-wk placebo (3 mL of fructose syrup) period, a 4-wk FOS (10 g/d) period, and a 4-wk post-FOS period. Stools were collected during the last week of each period to determine the microflora and fecal weight. Fasting blood was collected at the end of each period and analyzed for thiobarbituric acid-reactive substances (TBARS) and biochemical indices. RESULTS: Fecal counts (log counts/gram of dry feces) and daily fecal output of bifidobacteria significantly increased with FOS compared with placebo. The effect on bifidobacteria output was sustained in the post-FOS period. Plasma TBARS concentration was reduced by 16% and 21% in the FOS and post-FOS periods, respectively, compared with that in the placebo period. The plasma cholesterol level was significantly lowered by 7% in the FOS and post-FOS periods compared with that in the placebo period. The increases in fecal bifidobacteria output during the FOS period (log colony forming units per day) were associated with decreases in plasma TBARS and plasma cholesterol, respectively. CONCLUSION: Supplementation of FOS increases the daily output of bifidobacteria and decreases plasma TBARS and cholesterol concentrations in constipated nursing-home elderly residents and these effects remained at the end the post-FOS period. PMID- 20579849 TI - Vitamin C supplementation in patients receiving peripheral parenteral nutrition after gastrointestinal surgery. AB - OBJECTIVE: We investigated an adequate vitamin C dose during peripheral parenteral nutrition therapy in patients after gastrointestinal surgery by measuring blood concentrations and urine excretions of vitamin C. We also sought to identify the effects of vitamin C on the oxidative status. METHODS: In a randomized trial, 2 d after undergoing gastrointestinal surgery, 16 patients started to receive a 5-d continuous intravenous infusion of vitamin C, either 100 or 500 mg/d. Blood concentrations of vitamin C and inflammatory and immunologic parameters were measured preoperatively, the day after surgery, and 3 and 5 d after starting administration of vitamin C (day 3 and day 5). Also, excretions of vitamin C and oxidative stress markers in 24-h, cumulative urine samples, collected and stored under light protection at 0 degrees C, were measured on day 3 and day 5. RESULTS: Mean blood vitamin C concentration decreased markedly after surgery. The concentration returned to normal on day 3 and on day 5 in the 500-mg group and only on day 5 in the 100-mg group. Concentrations differed significantly between the groups on day 3 and on day 5 (P < 0.001 for both days). Urinary vitamin C excretion was above normal on both days in the 500-mg group, but it never reached normal in the 100-mg group (P < 0.001 for both days). Urinary excretion of 8-isoprostane, a marker of oxidative stress, was significantly lower in the 500-mg than in the 100-mg group on day 3 (P = 0.002). CONCLUSION: Vitamin C dose of 500 mg/d, not 100 mg/d, is adequate for patients undergoing gastrointestinal surgery and receiving peripheral parenteral nutrition therapy. Vitamin C may decrease postsurgical oxidative stress. PMID- 20579848 TI - No effects of low and high consumption of dairy products and calcium supplements on body composition and serum lipids in Puerto Rican obese adults. AB - OBJECTIVE: Epidemiologic studies have shown that a high calcium intake is related to lower body weight, fat, and serum lipids in obese individuals. However, clinical studies have shown inconclusive results. The present study was conducted to determine if dairy or calcium supplementation alters body composition or serum lipids in Puerto Rican obese adults without dietary energy restriction or exercise. METHODS: A 21-wk randomized clinical trial was conducted in 30 obese adults, aged 21-50 y, with usual calcium intakes <700 mg/d. Subjects were randomly assigned to the following: high dairy (~ 1300 mg/d of calcium from dairy products by substituting foods); high calcium (~ 1300 mg/d of calcium; ~ 700 mg/d from diet and 600 mg/d from a supplement); or placebo. Subjects were asked to continue their established dietary intake (except for the high dairy group) and their physical activity during the study. Body weight was measured monthly; body fat, bone, and serum lipids (total cholesterol, high-density lipoprotein, low density lipoprotein, and triacylglycerol) were measured at baseline and at 21 wk. Pairwise differences in study endpoints among the groups were assessed using ANOVA and post-hoc analysis. RESULTS: Grand mean calcium intake was 1200 +/- 370 (median 1187) mg/d in the high dairy group, 1171 +/- 265 (median 1165) mg/d in the high calcium group, and 668 +/- 273 (median 691) mg/d in the control group, which was significantly lower compared to the two treatment groups (P < 0.001). There were no significant group effects in any of the outcome variables. CONCLUSION: A high dairy or calcium diet alone did not alter body composition or serum lipids profile in a sample of Puerto Rican obese adults. PMID- 20579850 TI - Validation of a food-frequency questionnaire for Flemish and Italian-native subjects in Belgium: The IMMIDIET study. AB - OBJECTIVE: To validate an integrated food-frequency questionnaire (FFQ) developed to assess habitual food intake of Flemish and Italian-native subjects in Belgium as part of the European Collaborative Dietary Habit Profile in European Communities With Different Risk of Myocardial Infarction: the Impact of Migration as a Model of Gene/Environment Interaction (IMMIDIET Project). METHODS: The semiquantitative FFQ contained 322 items on food and food preparation. FFQs filled by a sample (n = 70) of the Flemish-Flemish and Flemish-Italian IMMIDIET subpopulations were randomly selected. Five 24-h recalls, administered over a period of 1 y by the same sample, served for validation. Energy and macronutrients were calculated using the Dutch NEVO and the Belgian NUBEL food composition tables. Intakes of energy and macronutrients estimated by the FFQ and repeated 24-h recall, respectively, were compared by means of correlation coefficients, classification into quartiles, and Bland-Altman plotting. RESULTS: The FFQ overestimated intake of energy and most macronutrients by 40-70%. This overestimation largely disappeared when values were expressed as energy percentage. Correlations ranked from 0.40 to 0.60 for energy and most macronutrients (median 0.53); correlations were lower (null to 0.41) for fat and higher (up to 0.90) for alcohol. Classification in quartiles of intake showed good agreement: 83% were classified in the same or adjacent quartile of energy, and 66-90% for macronutrients. Correlations and classification of macronutrient intake into quartiles remained similar when macronutrients were expressed as energy percentage. Stratification according to ethnic subgroup, age, body mass index, or social status showed no differences. CONCLUSION: The IMMIDIET FFQ is a valuable tool for studies of the role of energy and macronutrients in disease etiology or outcome, but less suitable for estimating absolute intake levels. PMID- 20579851 TI - Meal-induced thermogenesis and macronutrient oxidation in lean and obese women after consumption of carbohydrate-rich and fat-rich meals. AB - OBJECTIVE: To examine differences in meal-induced thermogenesis and macronutrient oxidation between lean and obese women after consumption of two different isocaloric meals, one rich in carbohydrate (CHO) and one rich in fat. METHODS: A total of 19 lean and 22 obese women were studied on two occasions, 1 wk apart. In one visit they consumed a CHO-rich meal and in the other visit a fat-rich meal. The two meals were isocaloric and were given in random order. Resting energy expenditure and macronutrient oxidation rates were measured and calculated in the fasting state and every hour for 3 h after meal consumption. RESULTS: Meal induced thermogenesis was not different between lean and obese subjects after the CHO-rich (P = 0.89) or fat-rich (P = 0.32) meal, but it was significantly higher after the CHO-rich compared with the fat-rich meal in the lean and the obese individuals (P < 0.05). Protein oxidation rate increased slightly but significantly after the test meals in both groups (P < 0.01). Fat oxidation rate decreased after consumption of the CHO-rich meal (P < 0.001), whereas it increased after consumption of the fat-rich meal in both groups (P < 0.01). CHO oxidation rate increased in both groups after consumption of the CHO-rich meal (P < 0.001). Oxidation rates of protein, fat, and CHO during the experiment were not significantly different between lean and obese participants. CONCLUSION: Meal induced thermogenesis and macronutrient oxidation rates were not significantly different between lean and obese women after consumption of a CHO-rich or a fat rich meal. PMID- 20579852 TI - Tessier type 3 oblique facial cleft with a contralateral complete cleft lip and palate. AB - Oblique facial clefts are extremely rare congenital deformities with a reported incidence of 0.24% of all facial clefts. This report presents a patient with a right-sided oblique cleft extending through the upper lip, the alar groove and the lower palpebra accompanied by a left-sided complete cleft lip and palate. Hypertylorism and bilateral microphthalmia as well as flexion wrist contractures were also present. Primary straight-line closure of the oblique cleft was undertaken followed by primary closure of the contralateral cleft lip. The treatment modality and 2 year follow-up results are presented. PMID- 20579853 TI - Cancer genes alterations and HPV infection in oral squamous cell carcinoma. AB - The aim of this study was to gain a better understanding of cancer genes contributing to oral squamous cell (OSCC) development and progression and correlate genetic changes to clinical parameters. Human papilloma virus (HPV) 16 detection is also included in the study. 60 samples of OSCC were analysed for c erbB2 and c-myc amplification by dPCR, H-ras and p53 point mutations by PCR/SSCP. HPV was detected via amplification of its E1 and E6 genes. c-erbB2 was altered in 45%, c-myc in 35%, H-ras in 22% and p53 in 60% of samples. HPV was detected in 10% of cases. The frequency of p53 gene mutations showed a statistically significant association with tumour stage. Patients with c-erbB2 and H-ras alterations had lower survival than patients without these alterations. The number of detected genetic changes was remarkable but statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis. PMID- 20579854 TI - Heart rate on admission is an independent risk factor for poor cardiac function and in-hospital death after acute myocardial infarction. AB - BACKGROUND: Increased resting heart rate (HR) due to sympathetic hyperactivity is associated with coronary risk factors and increased cardiovascular events. Acute myocardial infarction (AMI) is accompanied by autonomic imbalance, which is characterized by sympathetic activation and parasympathetic inactivation. Although an increased HR in patients with acute coronary syndrome has been reported to be associated with 30-day and 6-month mortality before the coronary intervention era, it is unclear if an increased HR on admission is associated with the prognosis of AMI in the coronary intervention era. METHODS: We enrolled 200 consecutive patients with AMI within 24 h of symptom onset. All patients underwent coronary angiography. They were divided into quartiles based on resting HR on admission. RESULTS: There was no difference in coronary risk factors and previous medical treatment among the four groups. Anterior AMI was significantly lower in the lowest quartile compared with other quartiles. There was no difference in peak creatine kinase value among the four groups, however left ventricular ejection fraction (LVEF) before discharge evaluated by echocardiography in the highest quartile group was significantly reduced compared to other quartiles. An increased HR was significantly associated with in-hospital death. Patients in the highest quartile of HR were about nine times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. Multiple logistic analysis revealed that HR >=93 was an independent risk factor for in-hospital death. HR was significantly associated with Killip class and LVEF on admission. CONCLUSIONS: These findings indicate that increased HR on admission predicts for poor cardiac function and in-hospital death after AMI. PMID- 20579856 TI - Microscopic structural analysis of fractured silk fibers from Bombyx mori and Samia cynthia ricini using 13C CP/MAS NMR with a 1mm microcoil MAS NMR probehead. AB - Conformational changes have been studied in silk fibers from the domestic silkworm Bombyx mori and a wild silkworm Samia cynthia ricini as a result of fractured by stretching. About 300 samples consisting of only the fractured regions of [1-13C]Ala or [1-13C]Gly labeled silk fibers were collected and observed by 13C CP/MAS NMR spectra. The total amount of these fractured fibers is only about 1mg and therefore we used a home-built 1mm microcoil MAS NMR probehead. A very small increase in the fraction of random coil was noted for the alanine regions of both silk fibroins and for the glycine region of B. mori silk fibroin. However, there is no difference in the spectra before and after fractured for the glycine region of S. c. ricini silk fibroin. Thus, the influence of fracture occurs exclusively at the Ala region for S. c. ricini. The relationship between sequence, fracture and structure is discussed. PMID- 20579857 TI - Dual-response nanocarrier based on graft copolymers with hydrazone bond linkages for improved drug delivery. AB - Core-shell micelles with biodegradability, thermo- and pH-response were successfully demonstrated by poly(2-oxepane-1,5-dione-co-epsilon-caprolactone) (P(OPD-co-CL)) grafted with hydrophilic segments of amine-terminated poly(N isopropylacrylamide) (At-PNIPAM). To compare with the graft copolymer, P(OPD-co CL) block PNIPAM polymer was also prepared. The micelles with core-shell structure were formed with both graft and block copolymers by self-assembly in aqueous solutions, of which PNIPAM shell is thermo-response. Furthermore, P(OPD co-CL)-g-PNIPAM also showed pH-sensitivity, which was attributed to the acid cleavable property of the hydrazone bond. The low critical micelle concentrations (CMCs) of graft polymers and block polymers were 6.7 mg/L and 14.3mg/L, respectively, which indicated the formation of stable micelles. Both drug-free and drug-loaded micelles were in uniformly spherical shape observed by transmission electron microscopy (TEM). The sizes of the drug-free and drug loaded micelles prepared from graft polymer were 123.5 nm and 146.5 nm, respectively, and the sizes of those prepared from block polymer were 197.5 nm and 211.5 nm, respectively. The lower critical solution temperature (LCST) for the graft polymer was 34.3 degrees C, while that for the block polymer was 28.1 degrees C, demonstrating a thermo-response. The graft polymeric micelles exhibited thermo-triggered decelerated release at pH 7.4, and pH-triggered accelerated release at 25 degrees C in vitro release test, indicating that the graft polymeric micelles could be a promising site-specific drug delivery system for enhancing the bioavailability of the drug in targeted pathological areas. PMID- 20579858 TI - Importance of dynamic culture for evaluating osteoblast activity on dense silicon substituted hydroxyapatite. AB - This paper reports an investigation on human osteoblast-like cells (SaOs-2) seeded onto pure hydroxyapatite (HA) and silicon-substituted HA (SiHA) tablets under static and dynamic culture conditions. The biological characterizations were conducted in classical static conditions in multi-wells plates, and in a perfusion bioreactor that permits continuous circulation of culture medium at 2 mL/h. The morphology, proliferation and differentiation of osteoblastic cells were examined for the two types of samples in the both culture conditions after 1, 3 and 8 days. Under dynamic conditions, cells cultured on SiHA surfaces showed a faster adhesion process and the formation of longer and thinner focal adhesions than in static conditions. The number of cells grown onto both ceramic surfaces was higher in dynamic conditions when compared with static conditions. Moreover, a higher activity of alkaline phosphatase was found for cells seeded under dynamic conditions. Our findings suggest that the application of perfusion culture system on cells cultured on dense substrates is valuable for predicting in vivo behaviour of cells on biomaterials. PMID- 20579855 TI - Disorganization and reality distortion in schizophrenia: a meta-analysis of the relationship between positive symptoms and neurocognitive deficits. AB - BACKGROUND: Factor analytic studies have shown that in schizophrenia patients, disorganization (e.g., conceptual disorganization and bizarre behavior) is a separate dimension from other types of positive symptoms such as reality distortion (delusions and hallucinations). Although some studies have found that disorganization is more strongly linked to neurocognitive deficits and poor functional outcomes than reality distortion, the findings are not always consistent. METHODS: A meta-analysis of 104 studies (combined n=8015) was conducted to determine the magnitude of the relationship between neurocognition and disorganization as compared to reality distortion. Additional analyses were conducted to determine whether the strength of these relationships differed depending on the neurocognitive domain under investigation. RESULTS: The relationship between reality distortion and neurocognition was weak (r=-.04; p=.03) as compared to the moderate association between disorganization and neurocognition (r=-.23; p<.01). In each of the six neurocognitive domains that were examined, disorganization was more strongly related to neurocognition (r's range from -.20 to -.26) than to reality distortion (r's range from .01 to -.12). CONCLUSIONS: The effect size of the relationship between neurocognition and disorganization was significantly larger than the effect size of the relationship between neurocognition and reality distortion. These results hold across several neurocognitive domains. These findings support a dimensional view of positive symptoms distinguishing disorganization from reality distortion. PMID- 20579859 TI - [Tumoral calcinosis: a case report]. AB - Tumoral calcinosis is a rare benign disease, defined by the presence of calcified deposits in periarticular tissues. The pathogenesis is unclear. We report a new case of tumoral calcinosis in a young girl, involving the left hip and both elbows. The clinical exam found a voluminous mass of soft tissues and the radiological exam showed the presence of voluminous periarticular calcifications with no bone involvement. The diagnosis was confirmed by the anatomopathological exam. The treatment remains essentially surgical and the prognosis is very good. PMID- 20579860 TI - Neurobehavioral and toxicological activities of two potentially CNS-acting medicinal plants of Piper genus. AB - Plants from the genus Piper are economically useful and some species have been indicated because of their medicinal properties in the central nervous system. However, few studies about toxicity and neurobehavioral effects have been conducted. In this study, two Piper species, P. amalago and P. mikanianum were investigated in rats to determine acute toxicity and to evaluate the ansiogenic/ansiolytic properties in the elevated plus-maze and the effects on locomotion and exploration in an open field. Additionally, genotoxic activities were evaluated, using the comet assay in several tissues and the micronucleus assay in bone marrow. The phytochemical analysis of both Piper species leaves suggests the presence of amide, essential oils, flavonoids and phenolic compounds. The LD(50) of P. amalago and P. mikanianum were estimated as 2,545 and 1,661 mg/kg, respectively. The behavioral and genotoxic parameters were determined after an intraperitoneal administration of P. amalago (250 or 420 mg/kg) or P. mikanianum (160 or 270 mg/kg). Both plants decreased the number of entries and time spent in the open arms in the plus-maze test, indicating an anxiogenic effect. Only P. mikanianum affected locomotion and exploration in the open field behavior test. No genotoxic or mutagenic effect was observed. Our results suggest that these Piper species act on the central nervous system, without induce genetic toxicity. PMID- 20579861 TI - Ursolic acid and oleanolic acid, members of pentacyclic triterpenoid acids, suppress TNF-alpha-induced E-selectin expression by cultured umbilical vein endothelial cells. AB - E-selectin is an early response adhesion molecule expressed on the surface of endothelial cells during inflammatory responses. We examined the effects of two pentacyclic triterpenoid acids, ursolic acid (UA) and oleanolic acid (OA), on the expression of E-selectin by cultured human umbilical vein endothelial cells (HUVECs). Treatment of the cells with UA or OA alone did not influence expression of E-selectin. Expression of E-selectin mRNA and surface antigen by HUVECs was induced by treatment with tumor necrosis factor-alpha (TNF-alpha) in a dose- and time-dependent manner. TNF-alpha-induced up-regulation of E-selectin was abrogated by pre-treatment of the cells with UA or OA which decreased expression of E-selectin mRNA. The repression of E-selectin mRNA expression caused by the pentacyclic triterpenoid acids paralleled the inhibition of NF-kappaB activation and nuclear translocation, as evaluated by electrophoretic mobility shift assays, although the degree of repression by UA was approximately two times more effective than that of OA. The results suggest that UA and OA suppress the inflammatory cytokine-induced expression of E-selectin in endothelial cells by decreasing E-selectin transcription via inhibition of NF-kappaB activation. Thus, UA and OA function as anti-inflammatory agents. The differences in the inhibitory efficacy between UA and OA may be due to conformational differences in ring-E of the two pentacyclic triterpenoid acids. PMID- 20579862 TI - Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus. AB - Oxidative stress contributes to the pathogenesis of diabetes mellitus and its sequelae nephropathy. The kidneys are especially prone to damage by free radicals. We therefore tested the effect of the flavonoid mixture silymarin, a free radical scavenger, on the activity and gene expression of superoxide dismutase, glutathione peroxidase and catalase, as well as on renal tissue morphology in rats with alloxan-induced diabetes mellitus. Alloxan-intoxicated rats were treated with silymarin 20 days after alloxan administration for 9 weeks. Alloxan-induced tissue damage and decreased the activity of the three enzymes, SOD (U/mg prot.): 14.4+/-1.75 vs 112+/-6.45 control, p<0.05, n=6; GSHPx (MUM NADPH/min/mg prot.): 0.02+/-0.002 vs 0.121+/-0.01 control, p<0.05, n=6; CAT (k/seg/mg prot.): 0.022+/-0.003 vs 0.044+/-0.002 control, p<0.05, n=6. Silymarin treatment prevented tissue damage and restored the activity (SOD: 110.7+/ 12.9U/mg prot.; GSHPx: 0.329+/-0.031 MUM NADPH/min/mg prot.; CAT: 0.054+/-0.002 k/seg/mg prot., n=6) and gene expression of the three antioxidant enzymes after 20 days of alloxan administration (SOD: 12.00+/-0.57 control, 9.00+/-0.1 diabetic p<0.05, 11.00+/-0.20 silymarin treated; GSHPx: 6.01+/-0.78 control, 9.03+/-0.3 diabetic p<0.05, 7.02+/-0.07 silymarin treated; CAT: 9.03+/-1.07 control, 12.02+/ 0.60 diabetic p<0.05, 8.06+/-0.31 silymarin treated, n=6). It is suggested in this study that recuperative effect of silymarin on the renal tissue damage induced by alloxan may be related to an increase in the activity and recovery of gene expression of antioxidant enzymes which in addition to the glutathione system constitute some of the most important defense mechanisms against free radicals damage. As these results show, silymarin may be considered potentially in the treatment of diabetic nephropathy. PMID- 20579863 TI - Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study. AB - The aim of this study was to evaluate the clinical efficacy of standardized French maritime pine bark extract Pycnogenol in patients with severe chronic venous insufficiency (CVI). 98 subjects with symptomatic CVI and edema were randomly assigned to one group treated with 150 mg Pycnogenol a day only, another group with stockings only and a third group with both Pycnogenol and elastic stockings. The average ambulatory venous pressure (AVP) at inclusion was 58+/-7 mm Hg (range 48-60 mm Hg) with a refilling time (RT)<12 s (average 7+/-2 s). The duration of the disease was on average 6.0+/-3.1 years. There were no differences in AVP or RT among the 3 groups at inclusion and microcirculatory and clinical evaluations were comparable. After 8 weeks treatment there was a significant decrease of rate of ankle swelling, resting flux, transcutaneous pO(2) and clinical symptom scores in all groups with significantly better results for the combination treatment. Pycnogenol alone was more effective than compression alone for all parameters (p<0.05). No side-effects were observed; compliance and tolerability were very good. This study corroborates a significant clinical role for Pycnogenol in the management, treatment and control of CVI also in combination with compression. PMID- 20579864 TI - Serum adipocyte-specific fatty acid-binding protein is associated with nonalcoholic fatty liver disease in apparently healthy subjects. AB - Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein that is expressed in adipocytes and is closely associated with insulin resistance, metabolic syndrome, and Type 2 diabetes. We investigated the relationship between A-FABP as a surrogate marker of metabolic syndrome and non alcoholic fatty liver disease (NAFLD) in apparently healthy subjects. We assessed clinical and biochemical metabolic parameters and measured serum levels of A FABP, high-sensitivity C-reactive protein and tumor necrosis factor-alpha (TNF alpha) in 494 subjects who were divided into two groups according to the presence of NAFLD by abdominal ultrasonography. All parameters associated with metabolic syndrome were significantly higher in patients with NAFLD (P<.001). A-FABP showed positive correlation with TNF-alpha, homeostasis model assessment index of insulin resistance (HOMA-IR), and metabolic syndrome (P<.001) when adjusted for age and sex. The odds ratio for the risk of NAFLD in the highest tertile of A FABP compared with the lowest tertile was 7.36 (CI 3.80-14.27, P<.001) after adjustment for age and sex; 4.52 (CI 2.22-9.20, P<.001) after adjustment for age, sex, HOMA-IR and metabolic syndrome and 2.86 (CI 1.11-7.35, P<.05) after further adjustment for all metabolic parameters including TNF-alpha. The serum level of A FABP was independently associated with NAFLD and showed significant correlation with TNF-alpha, HOMA-IR, and metabolic syndrome. PMID- 20579865 TI - A functional promoter polymorphism -607G>C of WNT10B is associated with abdominal fat in Korean female subjects. AB - WNT10B has been implicated as a potential regulator of adipogenesis in cellular and animal models of obesity. In this study, we attempted to characterize the associations between common genetic polymorphisms of WNT10B and fat accumulation in a sample of 1029 Korean female subjects. Direct sequencing of genomic DNAs of 45 subjects identified six common single-nucleotide polymorphisms (SNPs) of WNT10B, which were in almost complete linkage disequilibrium. Among the six SNPs, -607G>C (rs833840) showed differential nuclear factor binding in an electrophoretic mobility shift assay and differential promoter activity in a reporter assay, implicating it as a functional regulatory SNP. When body compositions of the subjects determined using bio-impedance analysis were compared according to their -607G>C genotype, only body fat mass showed a significant association. Body masses of protein, mineral and water showed no association. For more accurate evaluation of the effects of -607G>C genotype on body fat, cross-sectional fat areas of the subjects measured by abdominal computed tomography were compared. Genotype of -607G>C was significantly associated with abdominal total fat and abdominal subcutaneous fat areas (P=.009 and P=.007 in recessive model, respectively). Of the 1029 subjects, 576 were treated with a 1 month very low calorie diet and changes of body weight and composition were compared with -607G>C genotype. No significant associations were evident. This study is the first report of the association of common genetic polymorphism of WNT10B with human fat accumulation. PMID- 20579866 TI - Differential effects of formononetin and cladrin on osteoblast function, peak bone mass achievement and bioavailability in rats. AB - Dietary soy isoflavones including genistein and daidzein have been shown to have favorable effects during estrogen deficiency in experimental animals and humans. We have evaluated osteogenic effect of cladrin and formononetin, two structurally related methoxydaidzeins found in soy food and other natural sources. Cladrin, at as low as 10 nM, maximally stimulated both osteoblast proliferation and differentiation by activating MEK-Erk pathway. On the other hand, formononetin maximally stimulated osteoblast differentiation at 100 nM that involved p38 MAPK pathway but had no effect on osteoblast proliferation. Unlike daidzein, these two compounds neither activated estrogen receptor in osteoblast nor had any effect on osteoclast differentiation. Daily oral administration of each of these compounds at 10.0 mg kg(-1) day(-1) dose to recently weaned female Sprague-Dawley rats for 30 consecutive days, increased bone mineral density at various anatomic positions studied. By dynamic histomorphometry of bone, we observed that rats treated with cladrin exhibited increased mineral apposition and bone formation rates compared with control, while formononetin had no effect. Cladrin had much better plasma bioavailability compared with formononetin. None of these compounds exhibited estrogen agonistic effect in uteri. Our data suggest that cladrin is more potent among the two in promoting parameters of peak bone mass achievement, which could be attributed to its stimulatory effect on osteoblast proliferation and better bioavailability. To the best of our knowledge, this is the first attempt to elucidate structure-activity relationship between the methoxylated forms of daidzein and their osteogenic effects. PMID- 20579867 TI - Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155. AB - In the present study the effect of quercetin and its major metabolites quercetin 3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1beta, interleukin 6, macrophage inflammatory protein 1alpha and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks. PMID- 20579868 TI - Engineered microbial systems for enhanced conversion of lignocellulosic biomass. AB - In order for plant biomass to become a viable feedstock for meeting the future demand for liquid fuels, efficient and cost-effective processes must exist to breakdown cellulosic materials into their primary components. A one-pot conversion strategy or, consolidated bioprocessing, of biomass into ethanol would provide the most cost-effective route to renewable fuels and the realization of this technology is being actively pursued by both multi-disciplinary research centers and industrialists working at the very cutting edge of the field. Although a diverse range of bacteria and fungi possess the enzymatic machinery capable of hydrolyzing plant-derived polymers, none discovered so far meet the requirements for an industrial strength biocatalyst for the direct conversion of biomass to combustible fuels. Synthetic biology combined with a better fundamental understanding of enzymatic cellulose hydrolysis at the molecular level is enabling the rational engineering of microorganisms for utilizing cellulosic materials with simultaneous conversion to fuel. PMID- 20579869 TI - A new look at calcium channel alpha2delta subunits. AB - The classical roles of alpha(2)delta proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane topology, but we find that they can form GPI-anchored proteins. Moreover alpha(2)delta-1 and alpha(2)delta-3 have been shown to have novel functions in synaptogenesis, independent of their effect on calcium channels. In neurons, the alpha(2)delta-1 subunits are present mainly in presynaptic terminals. Peripheral sensory nerve injury results in the up-regulation of alpha(2)delta-1 in dorsal root ganglion (DRG) neurons, and there is a consequent increase in trafficking of alpha(2)delta-1 to their terminals. Furthermore, gabapentinoid drugs, which bind to alpha(2)delta-1 and alpha(2)delta-2, not only impair their trafficking, but also affect alpha(2)delta-1-dependent synaptogenesis. These drugs may interfere with alpha(2)delta function at several different levels. PMID- 20579870 TI - Synthesis of methyl esters from relevant palm products in near-critical methanol with modified-zirconia catalysts. AB - The transesterification and esterification of palm products i.e. crude palm oil (CPO), refined palm oil (RPO) and palm fatty acid distillate (PFAD) under near critical methanol in the presence of synthesized SO(4)-ZrO(2), WO(3)-ZrO(2) and TiO(2)-ZrO(2) (with various sulfur- and tungsten loadings, Ti/Zr ratios, and calcination temperatures) were studied. Among them, the reaction of RPO with 20%WO(3)-ZrO(2) (calcined at 800 degrees C) enhanced the highest fatty acid methyl ester (FAME) yield with greatest stability after several reaction cycles; furthermore, it required shorter time, lower temperature and less amount of methanol compared to the reactions without catalyst. These benefits were related to the high acid-site density and tetragonal phase formation of synthesized WO(3) ZrO(2). For further improvement, the addition of toluene as co-solvent considerably reduced the requirement of methanol to maximize FAME yield, while the addition of molecular sieve along with catalyst significantly increased FAME yield from PFAD and CPO due to the inhibition of hydrolysis reaction. PMID- 20579871 TI - Nitritation and denitritation of domestic wastewater using a continuous anaerobic anoxic-aerobic (A(2)O) process at ambient temperatures. AB - In a continuous anaerobic-anoxic-aerobic (A(2)O) process treating domestic wastewater at ambient temperatures, nitritation was achieved through a combination of short aerobic actual hydraulic retention time (AHRT) and low dissolved oxygen (DO) levels (0.3-0.5mg/L). The nitrite accumulation rate was about 90% and ammonia removal efficiency was over 95%. With respect to total nitrogen removal, nitritation-denitritation at low DO levels of 0.3-0.5mg/L was essentially equal to the complete nitrification-denitrification at DO levels of 1.5-2.5mg/L with the addition of external carbon sources. Regardless of low DO operation, sludge bulking did not occur since the sludge volume index was below 150ml/g. Real-time PCR assays showed that in response to complete and partial nitrification modes, the numbers of ammonia oxidizing bacteria population were 5.28x10(9)cells/g MLVSS and 3.95x10(10)cells/g MLVSS, respectively. Achievement of nitritation-denitritation is highly beneficial to the treatment of domestic wastewater in terms of lower carbon requirements and reduced aeration costs. PMID- 20579872 TI - Disintegration of biological sludge: Effect of ozone oxidation and ultrasonic treatment on aerobic digestibility. AB - The present study deals with disintegration of biological sludge by ozone oxidation and ultrasonic treatment. The effects of ozone and ultrasonic treatment were investigated on aerobic sludge bio-processing as comparatively. 9690kJ/kg TS of specific energy and 0.1g O(3)/kg TS were applied to sludge samples preceding aerobic sludge digestion. In terms of sludge stabilization, the highest volatile solids reduction and protein degradation were obtained with ultrasonic treatment. Moreover, digesters fed with disintegrated sludge had higher bacterial activities in terms of oxygen uptake rate (OUR) and volatile suspended solids (VSS)/ suspended solids (SS) ratio than control one during the operation period. In terms of dewatering characteristics of digested sludge, ultrasonic treatment led to increase the sludge's resistance to dewatering. This negative effect was not observed in ozone oxidation. In addition, disintegration processes used in this study did not contribute to an improvement in cake solids on a crown press application. PMID- 20579873 TI - A high-throughput screening system for the evaluation of biomass-hydrolyzing glycoside hydrolases. AB - To implement a protein engineering strategy for the improvement of enzyme performance on biomass, a straightforward, robust high-throughput method was devised and tested with recombinant GH11 xylanase as acting on wheat straw. The method requires automated liquid handling equipment, but avoids the need for specialized milling and powder weighing devices and the use of labour intensive steps such as manual cutting of pipette tips. After expression in Escherichia coli cells grown in microtiter plates, recombinant xylanase was released into the culture medium and used directly for biomass hydrolysis. Reactions were monitored using a micro-3,5-dinitrosalicylic acid assay. The cumulative error of the method was less than 15%. To validate the method, randomly generated xylanase mutants were analyzed. This allowed the detection of one mutant, which produced a 74% increase in hydrolysis compared to the parental enzyme. Closer analysis revealed that this increase in activity was correlated with a twofold increase in xylanase expression. PMID- 20579874 TI - BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg 296. AB - Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease modifying therapy for Alzheimer's disease. Herein, is described a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296. PMID- 20579876 TI - Structure-activity relationship of indoline-2-carboxylic acid N (substituted)phenylamide derivatives. AB - Chroman derivatives exhibited potent inhibitory activity of NF-kappaB. For SAR, the chroman scaffold was modified with an indoline moiety. A series of indoline-2 carboxylic acid N-(substituted)phenylamide derivatives were synthesized to explore their inhibitory activities of NF-kappaB and they were also evaluated for cytotoxicity against various cancer cell lines. Since intermediates with Boc showed outstanding results, various substituents in place of the Boc group were introduced additionally and these compounds were also evaluated for SAR. PMID- 20579875 TI - Anibamine, a natural product CCR5 antagonist, as a novel lead for the development of anti-prostate cancer agents. AB - Accumulating evidence indicates that the chemokine receptor CCR5 and the chemokine CCL5 may be involved in the proliferation and metastasis of prostate cancer. Consequently, chemokine receptor CCR5 antagonists could potentially act as anti-prostate cancer agents. As the first natural product CCR5 antagonist, anibamine provides a novel chemical structural skeleton compared with other known antagonists identified through high-throughput screening. Our studies demonstrate that anibamine produces significant inhibition of prostate cancer cell proliferation at micromolar to submicromolar concentrations as well as suppressing adhesion and invasion of the highly metastatic M12 prostate cancer cell line. Preliminary in vivo studies indicate that anibamine also inhibits prostate tumor growth in mice. These findings indicate that anibamine may prove to be a novel lead compound for the development of prostate cancer therapeutic agents. PMID- 20579877 TI - Use of 2-[(18)F]fluoroethylazide for the Staudinger ligation - Preparation and characterisation of GABA(A) receptor binding 4-quinolones. AB - The labelling reagent 2-[(18)F]fluoroethylazide was used in a traceless Staudinger ligation. This reaction was employed to obtain the GABA(A) receptor binding 6-benzyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (2 [(18)F]fluoroethyl) amide. The radiotracer was prepared with a non-decay corrected radiochemical yield of 7%, a radiochemical purity >95% and a specific radioactivity of 0.9 GBq/micromol. The compound showed low brain penetration in normal rats. A series of fluoroalkyl 4-quinolone analogues with nanomolar to sub nanomolar affinity for the GABA(A) receptor has been prepared as well. PMID- 20579878 TI - Structure-activity relationships and in vivo activity of (1H-pyrazol-4 yl)acetamide antagonists of the P2X(7) receptor. AB - Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent antihyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res.1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain2006, 10, 537]. PMID- 20579879 TI - Regulation of Frizzled-dependent planar polarity signaling by a V-ATPase subunit. AB - Frizzled (Fz) is a seven-pass transmembrane receptor that acts in both Wingless (Wg) and planar cell polarity (PCP) pathways. A prerequisite for PCP signaling is the asymmetric subcellular distribution of Fz. However, the regulation of Fz asymmetry is currently not well understood. Here we describe that the transmembrane protein CG8444 (here termed VhaPRR) is needed for PCP signaling in Drosophila. VhaPRR is an accessory subunit of the vacuolar (V)-ATPase proton pump, but it also functions as a receptor for (pro)renin (PRR) in mammals. We show that VhaPRR function is tightly linked with Fz but not other PCP core proteins. Fz fails to localize asymmetrically in the absence of VhaPRR, and this is accompanied by prehair mispolarization of pupal wing cells. In addition, VhaPRR forms a protein complex with Fz receptors and interacts genetically with Fz in the Drosophila eye. VhaPRR also acts as a modulator of canonical Wnt signaling in larval and adult wing tissue. Its loss leads to an expansion of the Wg morphogen gradient and a reduction of Wg target gene expression. The requirement for additional V-ATPase subunits suggests that proton fluxes contribute to normal Fz receptor function and signaling. PMID- 20579880 TI - Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons. AB - BACKGROUND: Primary sensory neurons of the dorsal root ganglia (DRG) regenerate their spinal cord axon if the peripheral nerve axon has previously been cut. This conditioning lesion confers axon growth competence to the neurons. However, the signal that is sensed by the cell upon peripheral lesion to initiate the regenerative response remains elusive. RESULTS: We show here that loss of electrical activity following peripheral deafferentiation is an important signal to trigger axon regrowth. We first verified that firing in sensory fibers, as recorded from dorsal roots in vivo, declined after peripheral lesioning but was not altered after central lesioning. We found that electrical activity strongly inhibited axon outgrowth in cultured adult sensory neurons. The inhibitory effect depended on the L-type voltage-gated Ca(2+) channel current and involved transcriptional changes. After a peripheral lesion, the L-type current was consistently diminished and the L-type pore-forming subunit, Ca(v)1.2, was downregulated. Genetic ablation of Ca(v)1.2 in the nervous system caused an increase in axon outgrowth from dissociated DRG neurons and enhanced peripheral nerve regeneration in vivo. CONCLUSIONS: Our data indicate that cessation of electrical activity after peripheral lesion contributes to the regenerative response observed upon conditioning and might be necessary to promote regeneration after central nervous system injury. PMID- 20579882 TI - Male reproductive senescence causes potential for sexual conflict over mating. AB - The realization that senescence, age-dependent declines in survival and reproductive performance, pervades natural populations has brought its evolutionary significance into sharper focus. However, reproductive senescence remains poorly understood because it is difficult to separate male and female mechanisms underpinning reproductive success. We experimentally investigated male reproductive senescence in feral fowl, Gallus gallus domesticus, where socially dominant males monopolize access to females and the ejaculates of multiple males compete for fertilization. We detected the signal of senescence on multiple determinants of male reproductive success. The effect of age on status was dependent upon the intensity of intrasexual competition: old males were less likely to dominate male-biased groups where competition is intense but were as likely as young males to dominate female-biased groups. Mating and fertilization success declined sharply with male age largely as a result of population-level patterns. These age-dependent declines translated into sexually antagonistic payoffs: old males fertilized more eggs when they were dominant, but this resulted in females suffering a drastic reduction in fertility. Thus, male senescence causes potential for sexual conflict over mating, and the intensity of this conflict is modulated socially, by the probability of old males dominating reproductive opportunities. PMID- 20579881 TI - Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans. AB - MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the translation and/or stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single-gene knockouts did not result in detectable mutant phenotypes. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways. With these two approaches, we identified mutant phenotypes for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that the use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis. PMID- 20579883 TI - Wnt/Frizzled signaling requires dPRR, the Drosophila homolog of the prorenin receptor. AB - Wnt/Wg signaling pathways are of key importance during development and disease. Canonical and noncanonical Wnt/Frizzled (Fz) pathways share a limited number of signaling components that are part of the membrane proximal signaling complex. In Drosophila, Fz and Dishevelled (Dsh) are the only two components known to be involved in both Wnt/beta-catenin and planar cell polarity (PCP) signaling. PCP signaling is required for the planar polarization of epithelial cells, which occurs, for instance, during hair orientation and gastrulation in vertebrates. Both pathways have been studied intensively in the past years. However, it still remains unresolved whether additional components are required at the receptor complex. Here we identify the Drosophila homolog of the mammalian prorenin receptor (dPRR) as a conserved modulator of canonical Wnt/beta-cat and Fz/PCP signaling. We show that dPRR depletion affects Wg target genes in cultured cells and in vivo. PRR is required for epithelial planar polarity in Drosophila and for convergent extension movements in Xenopus gastrulae. Furthermore, dPRR binds to Fz and Fz2 receptors. In summary, our data suggest that dPRR has an evolutionarily conserved role at the receptor level for activation of canonical and noncanonical Wnt/Fz signaling pathways. PMID- 20579884 TI - Salmonella-directed recruitment of new membrane to invasion foci via the host exocyst complex. AB - Salmonella attachment to the intestinal epithelium triggers delivery of bacterial effector proteins into the host cytosol through a type III secretion system (T3SS), leading to pronounced membrane ruffling and macropinocytic uptake of attached bacteria. The tip of the T3SS is made up of two proteins, SipB and SipC, which insert into the host plasma membrane, forming a translocation pore. Both the N and C termini of SipC are exposed in the host cytosol and have been shown to directly modulate actin cytoskeleton assembly. We have identified a direct interaction between SipC and Exo70, a component of the exocyst complex, which mediates docking and fusion of exocytic vesicles with the plasma membrane. Here, we show that exocyst components coprecipitate with SipC and accumulate at sites of invasion by Salmonella typhimurium. Exocyst assembly requires activation of the small GTPase RalA, which we show is triggered during Salmonella infection by the translocated effector, SopE. Knockdown of RalA or Sec5 results in reduced membrane ruffling at sites of attachment and impairs bacterial entry into host cells. These findings suggest that S. typhimurium enhances invasion efficiency by promoting localized membrane expansion, directly through SipC-dependent recruitment of the exocyst and indirectly via SopE-dependent activation of RalA. PMID- 20579885 TI - Synergistic activation of phospholipase C-beta3 by Galpha(q) and Gbetagamma describes a simple two-state coincidence detector. AB - BACKGROUND: Receptors that couple to G(i) and G(q) often interact synergistically in cells to elicit cytosolic Ca(2+) transients that are several-fold higher than the sum of those driven by each receptor alone. Such synergism is commonly assumed to be complex, requiring regulatory interaction between components, multiple pathways, or multiple states of the target protein. RESULTS: We show that cellular G(i)-G(q) synergism derives from direct supra-additive stimulation of phospholipase C-beta3 (PLC-beta3) by G protein subunits Gbetagamma and Galpha(q), the relevant components of the G(i) and G(q) signaling pathways. No additional pathway or proteins are required. Synergism is quantitatively explained by the classical and simple two-state (inactive<-->active) allosteric mechanism. We show generally that synergistic activation of a two-state enzyme reflects enhanced conversion to the active state when both ligands are bound, not merely the enhancement of ligand affinity predicted by positive cooperativity. The two-state mechanism also explains why synergism is unique to PLC-beta3 among the four PLC-beta isoforms and, in general, why one enzyme may respond synergistically to two activators while another does not. Expression of synergism demands that an enzyme display low basal activity in the absence of ligand and becomes significant only when basal activity is 1 mM resulting in a selectivity index (SI=CC50/EC50)>21. The most efficient replication inhibitor, 3,5,7-tri[(4'-methylpiperidin-1' yl)methyl]tropolone (6), inhibited RNA replication with an EC50 of 32.0 microM and a SI value of 17.4, whereas 3,5,7-tri[(3'-methylpiperidin-1' yl)methyl]tropolone (7) exhibited a slightly lower activity with an EC50 of 35.6 microM and a SI of 9.8. PMID- 20579889 TI - A novel achiral seco-cyclopropylpyrido[e]indolone (CPyI) analog of CC-1065 and the duocarmycins: synthesis, DNA interactions, in vivo anticancer and anti parasitic evaluation. AB - The synthesis of an achiral seco-hydroxy-aza-CBI-TMI analog (8) of the duocarmycins is reported. Its specificity for the DNA minor groove of AT-rich sequences and covalent bonding to adenine-N3 was ascertained by a thermal cleavage assay. Compound 8 was found to be cytotoxic in the nanomolar range against murine and human cancer cells. It was further demonstrated that compound 8 was active against murine melanoma (B16-F0) grown in C57BL/6 mice. Compound 8 was also shown to inhibit the growth of the protozoan parasites Leishmania donovani, Leishmania mexicana, Trypanosoma brucei, and Plasmodium falciparum in culture. PMID- 20579890 TI - Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors. AB - The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds. PMID- 20579891 TI - Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors. AB - The central role of microtubules in cell division and mitosis makes them a particularly important target for anticancer agents. On our early publication, we found that a series of 2-(3',4',5'-trimethoxybenzoyl)-3-aminobenzo[b]thiophenes exhibited strong antiproliferative activity in the submicromolar range and significantly arrested cells in the G2-M phase of the cell cycle and induced apoptosis. In order to investigate the importance of the amino group at the 3 position of the benzo[b]thiophene skeleton, the corresponding 3-unsubstituted and methyl derivatives were prepared. A novel series of inhibitors of tubulin polymerization, based on the 2-(3,4,5-trimethoxybenzoyl)-benzo[b]thiophene molecular skeleton with a methoxy substituent at the C-4, C-5, C-6 or C-7 position on the benzene ring, was evaluated for antiproliferative activity against a panel of five cancer cell lines, for inhibition of tubulin polymerization and for cell cycle effects. Replacing the methyl group at the C-3 position resulted in increased activity compared with the corresponding 3 unsubstituted counterpart. The structure-activity relationship established that the best activities were obtained with the methoxy group placed at the C-4, C-6 or C-7 position. Most of these compounds exhibited good growth inhibition activity and arrest K562 cells in the G2-M phase via microtubule depolymerization. PMID- 20579892 TI - Tryptamine-derived alkaloids from Annonaceae exerting neurotrophin-like properties on primary dopaminergic neurons. AB - N-fatty acyl tryptamines constitute a scarce group of natural compounds mainly encountered in Annonaceous plants. No biological activity was reported so far for these rare molecules. This study investigated the neurotrophic properties of these natural tryptaminic derivatives on dopaminergic (DA) neurons in primary mesencephalic cultures. A structure-activity relationships study led us to precise the role of a nitrogen atom into the aliphatic chain conferring to the compounds a combined neuroprotective and neuritogenic activity in the nanomolar range. The potent antioxidant activity of these natural products seems to be involved in part of their mechanism of action. This study provides the first description of natural neurotrophin mimetics present in Annonaceae extracts, and led to the biological characterization of compounds, which present a potential interest in neurodegenerative diseases such as Parkinson's disease. PMID- 20579893 TI - Enhancement of hydrogen gas permeability in electrically aligned MWCNT-PMMA composite membranes. AB - The multi-walled carbon nanotube (MWCNT) dispersed polymethylmethacrylate (PMMA) composite membranes have been prepared for hydrogen gas permeation application. Composite membranes are characterized by Raman spectroscopy, optical microscopy, X-ray diffraction, electrical measurements and gas permeability measurements. The effect of electric field alignment of MWCNT in PMMA matrix on gas permeation has been studied for hydrogen gas. The permeability measurements indicated that the electrically aligned MWCNT in PMMA has shown almost 2 times higher permeability for hydrogen gas as compare to randomly dispersed MWCNT in PMMA. The enhancement in permeability is explained on the basis of well aligned easy channel provided by MWCNT in electrically aligned sample. The effect of thickness of membrane on the gas permeability also studied and thickness of about 30microm found to be optimum thickness for fast hydrogen gas permeates. PMID- 20579894 TI - (99m)Tc-labeled-1-thio-beta-d-glucose as a new tool to temporomandibular joint inflammatory disorders diagnosis. AB - AIM: The aim of this study was to evaluate early detection of temporomandibular joint (TMJ) inflammatory changes based on 1-thio-beta-d-glucose radiolabeled with technetium-99m. METHOD: The method applied a TMJ inflammation model in rats followed by radiopharmaceutical synthesis, intravenous administration of (99m)Tc 1-TG and kinetic scintigraphy imaging. RESULTS: Results show a significant difference of (99m)Tc-1-TG uptake between inflamed TMJ and the control joint. The biodistribution of (99m)Tc-1-TG by images showed the kidneys' excretion. CONCLUSION: As conclusion, (99m)Tc-1-TG is a helpful tool in TMJ inflammatory process detection. PMID- 20579895 TI - Electron paramagnetic resonance. Preface. PMID- 20579896 TI - Effects of admixture gas on the production of (18)F radioisotope in plasma focus devices. AB - In this article, the effect of admixture gas on the heating and cooling of pinched plasma directly related to the enhancement or reduction of (18)F production through the (16)O((3)He, p)(18)F is considered in the plasma focus devices. It is shown that by controlling the velocity of added Oxygen particles mixed with the working helium gas into the plasma focus chamber, one can increase the current and decrease the confinement time (plasma heating) or vice verse (plasma cooling). The highest level of nuclear activities of (18)F was found around 16% of the Oxygen admixture participation and was about 0.35 MBq in the conditions of 20 kJ, 0.1 Hz and after 2 min operating of Dena PF. However, in the same condition, but for the frequency of 1 Hz, the level of activity increased up to 3.4 MBq. PMID- 20579897 TI - Anterolateral thigh skinfold thickness and the European head and neck cancer patient: a prospective study. AB - The purpose of this study was to objectively assess this widely recognised problem of the bulky adipocutaneous Anterolateral thigh flap in the European population that may have implications in the reconstruction of head and neck cancer patients. We report 50 cases that underwent specific prospective thigh skinfold thickness assessment as part of assessment of suitability for ALT flap reconstruction following cancer ablation. The null hypothesis was that thigh skinfold thickness and circumference in an oral cancer population do not differ significantly from published sino-Asian norms. This study confirms anthropometrically the suspicion that European thigh skinfold thickness in a head and neck cancer population is greater than sino-Asian comparators. PMID- 20579898 TI - The impact of sequential grafting on clinical outcomes following coronary artery bypass grafting. AB - OBJECTIVES: Sequential anastomoses in coronary artery bypass grafting (CABG) offer theoretical advantages including increased graft flow and more complete revascularisation. However, published studies concerning the safety and efficacy of this technique are not definitive. The objective of this study was to assess the effect of sequential anastomoses on outcomes following CABG. METHODS: Perioperative data were prospectively collected on all patients with triple vessel disease who underwent first-time, isolated, on-pump CABG between 1995 and 2005 at a single centre. Patients with a left internal mammary artery graft to the anterior wall and saphenous vein grafts to the lateral and posterior walls were included. RESULTS: Compared to patients without sequential anastomoses (n=1108), patients with sequential anastomoses (n=1246) were more likely to have an ejection fraction (EF)<40% (14.9% vs 10.8%, p=0.004), a recent myocardial infarction (19.3% vs 14.3%, p=0.001) and an urgent/emergent operative status (19.6% vs 14.4%, p=0.0008). Median follow-up was 78 months. After adjusting for clinical covariates, sequential grafting was not an independent predictor of in hospital adverse events (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.88 1.50, p=0.31) or long-term mortality and/or readmission to hospital (hazard ratio (HR) 0.98, 95% CI 0.86-1.12, p=0.74). Sequential grafting was an independent predictor of receiving greater than three distal anastomoses (OR 9.26, 95% CI; 6.27-13.67, p<0.0001). CONCLUSIONS: Patients undergoing sequential grafting presented with greater acuity and worse systolic function. After adjusting for baseline differences, sequential grafting was not found to be an independent predictor of adverse events. These results support the safety of sequential anastomoses in patients undergoing CABG. PMID- 20579900 TI - Mediastinal thoracic duct cyst adjacent to left pericardium. PMID- 20579901 TI - Vitamin D status in psoriasis patients during different treatments with phototherapy. AB - BACKGROUND: Phototherapy (broadband UVB (BUVB), narrowband UVB (NBUVB) and heliotherapy) is commonly used treatment modalities for widespread psoriasis. Vitamin D3, cholecalciferol, is produced in the epidermis by ultraviolet radiation (290-315 nm) of 7-dehydrocholesterol. 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] are the major circulating metabolites. Sun exposure is the strongest factor influencing 25(OH)D. The similar wavelength spectrum of UVB responsible for D vitamin synthesis (BUVB, 280-315 nm) has been successfully used for years to treat psoriasis. PURPOSE: The aim was: (1) To increase the knowledge about the effects of phototherapy on vitamin D production during treatment of psoriasis. (2) To examine if there were differences between the effect of BUVB, NBUVB and heliotherapy on vitamin D synthesis in psoriasis patients. METHODS: Serum concentrations of 25(OH)D, 1,25(OH)(2)D, PTH, calcium and creatinine, measured before and after phototherapy in white Caucasian patients with moderate to severe active plaque psoriasis, were aggregated from three studies. RESULTS: Psoriasis improved in all patients, with a reduction in PASI ((Psoriasis Area and Severity Index) score of about 75% on all regimes. Serum 25(OH)D increased and PTH decreased after the phototherapy. The increase in 25(OH)D was higher in the BUVB treated patients compared with NBUVB. There was no correlation between the dose of UVB and the increase of 25(OH)D. CONCLUSION: UVB and heliotherapy improved the psoriasis score, increased the serum 25(OH)D levels and reduced the serum PTH concentrations. Vitamin D production in psoriasis patients increased less with NBUVB than with BUVB phototherapy. PMID- 20579902 TI - Comorbidity, not age, is prognostic in patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy. AB - OBJECTIVE: To evaluate the impact of age and comorbidity on clinical outcomes in advanced pancreatic cancer. METHODS: Consecutive 237 patients with advanced pancreatic cancer were studied. Comorbidity was scored by Charlson comorbidity index (CCI). We compared the clinical outcomes by age or comorbidity. RESULTS: Sixty-nine patients were elderly (>=75 years), and CCI was 0 in 69 patients, 1 in 98, and >=2 in 70. Gemcitabine-based chemotherapy was administered in 183 patients and was well tolerated in both elderly group and in those with comorbidities. In a multivariate analysis, CCI, not age, was prognostic in addition to PS, distant metastasis, chemotherapy and CA19-9: the hazard ratios of CCI 1 and >=2 were 1.25 and 1.55, compared with CCI 0 (p=0.027). CONCLUSIONS: Gemcitabine-based chemotherapy can be an effective treatment, without significant toxicity, in elderly patients. Comorbidity, not age, was prognostic in patients with advanced pancreatic cancer. PMID- 20579903 TI - Detecting differentially expressed genes: minimizing burden of testing and maximizing number of discoveries. AB - PURPOSE: Recent progress in DNA microarray technologies allows researchers to perform genome-wide screening to detect differentially expressed genes. Under the paradigm of false discovery rate control, this paper presents sample size methods. METHODS: The author considers the following two scenarios: 1) planning the sample size to keep the 'burden of testing' (defined as the expected number of genes that have to be tested before a true discovery can be made) below a certain level, and 2) given a fixed amount of budget, balancing the number of subjects to be recruited and the number of genes to be tested to maximize the total number of true discoveries. RESULTS: The study calculates sample sizes to minimize the burden of testing or to maximize the number of discoveries. CONCLUSIONS: The present approach to sample size calculation bears more direct relevance to gene-discovery studies. PMID- 20579904 TI - Walking pace, leisure time physical activity, and resting heart rate in relation to disease-specific mortality in London: 40 years follow-up of the original Whitehall study. An update of our work with professor Jerry N. Morris (1910 2009). AB - PURPOSE: To examine the association of leisure time physical activity, walking pace and resting heart rate with disease-specific mortality in a prospective cohort study by reporting updated analyses of an earlier report we produced with the British epidemiologist, Jerry N. Morris (1910-2009). METHODS: In the original Whitehall study, 19,019 male, nonindustrial, London-based government employees, aged from 40 to 69 years in 1967 and 1970, participated in a medical examination during which data on leisure time physical activity (N = 6715), self-rated walking pace (N = 6729), and resting heart rate (N = 1183) were collected. Cox proportional hazards analyses were used to estimate hazard ratios for the relation between these exposures and disease-specific mortality. RESULTS: In models adjusted for a range of covariates including socioeconomic status, smoking, and obesity, high resting heart rate was associated with a modestly elevated rate of mortality from all causes (hazard ratio; 95% confidence interval: tertile 3 vs. tertile 1: 1.17; 0.99, 1.37 p[trend]: 0.07) and respiratory disease (1.69; 1.04, 2.76 p[trend]: 0.03). Of the two markers of physical activity, walking pace was inversely related to mortality ascribed to all causes (slow vs. high walking pace 1.71; 1.53, 1.91 p[trend]: <0.001]), coronary heart disease (2.03; 1.68, 2.47 p[trend]: <0.001), and total cancers (1.25; 0.98, 1.59 p[trend]: 0.04). The corresponding associations for leisure time activity were typically weaker. For other mortality endpoints-respiratory disease (walking pace: 1.96; 1.48, 2.60 p[trend]: <0.001]), hematopoietic cancer (walking pace: 1.36; 0.52, 3.51 p[trend]: 0.03), stomach cancer (inactive versus active leisure time: 1.53; 0.88, 2.64 p[trend]: 0.04), and rectal cancer (walking pace: 4.85; 1.70, 13.8 p[trend]: 0.007)-individual activity indices revealed effects, but not both. CONCLUSIONS: Higher levels of physical activity indexed by the various markers herein appeared to confer protection against a range of mortality outcomes. PMID- 20579906 TI - sEMG wavelet-based indices predicts muscle power loss during dynamic contractions. AB - The purpose of this study was to investigate the sensitivity of new surface electromyography (sEMG) indices based on the discrete wavelet transform to estimate acute exercise-induced changes on muscle power output during a dynamic fatiguing protocol. Fifteen trained subjects performed five sets consisting of 10 leg press, with 2 min rest between sets. sEMG was recorded from vastus medialis (VM) muscle. Several surface electromyographic parameters were computed. These were: mean rectified voltage (MRV), median spectral frequency (F(med)), Dimitrov spectral index of muscle fatigue (FI(nsm5)), as well as five other parameters obtained from the stationary wavelet transform (SWT) as ratios between different scales. The new wavelet indices showed better accuracy to map changes in muscle power output during the fatiguing protocol. Moreover, the new wavelet indices as a single parameter predictor accounted for 46.6% of the performance variance of changes in muscle power and the log-FI(nsm5) and MRV as a two-factor combination predictor accounted for 49.8%. On the other hand, the new wavelet indices proposed, showed the highest robustness in presence of additive white Gaussian noise for different signal to noise ratios (SNRs). The sEMG wavelet indices proposed may be a useful tool to map changes in muscle power output during dynamic high-loading fatiguing task. PMID- 20579905 TI - Multi-dimensional risk factor patterns associated with non-use of highly active antiretroviral therapy among human immunodeficiency virus-infected women. AB - OBJECTIVES: Relationships between non-use of highly active antiretroviral therapy (HAART), race/ethnicity, violence, drug use, and other risk factors are investigated using qualitative profiles of five risk factors (unprotected sex, multiple male partners, heavy drinking, crack, cocaine or heroin use, and exposure to physical violence) and association of the profiles and race/ethnicity with non-use of HAART over time. METHODS: A hidden Markov model was used to summarize risk factor profiles and changes in profiles over time in a longitudinal sample of HIV-infected women enrolled in the Women's Interagency HIV Study with follow-up from 2002 to 2005 (n = 802). RESULTS: Four risk factor profiles corresponding to four distinct latent states were identified from the five risk factors. Trajectory analysis indicated that states characterized by high probabilities of all risk factors or by low probabilities of all risk factors were both relatively stable over time. Being in the highest risk state did not significantly elevate the odds of HAART non-use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.6-1.8). However, being in a latent state characterized by elevated probabilities of heavy drinking and exposure to physical violence, along with slight elevations in three other risk factors, significantly increased odds of HAART non-use (OR, 1.4; 95% CI, 1.1-1.9). CONCLUSION: The research suggests that HAART use might be improved by interventions aimed at women who are heavy drinkers with recent exposure to physical violence and evidence of other risk factors. More research about the relationship between clustering and patterns of risk factors and use of HAART is needed. PMID- 20579907 TI - Addition of isolated wrist extensor eccentric exercise to standard treatment for chronic lateral epicondylosis: a prospective randomized trial. AB - BACKGROUND: Isokinetic eccentric training of the wrist extensors has recently been shown to be effective in treating chronic lateral epicondylosis. However, isokinetic dynamometry is not widely available or practical for daily exercise prescription. Therefore, the objective of this study was to assess the efficacy of a novel eccentric wrist extensor exercise added to standard treatment for chronic lateral epicondylosis. MATERIALS AND METHODS: Twenty-one patients with chronic unilateral lateral epicondylosis were randomized into an eccentric training group (n = 11, 6 men, 5 women; age 47 +/- 2 yr) and a Standard Treatment Group (n = 10, 4 men, 6 women; age 51 +/- 4 yr). DASH questionnaire, VAS, tenderness measurement, and wrist and middle finger extension were recorded at baseline and after the treatment period. RESULTS: Groups did not differ in terms of duration of symptoms (Eccentric 6 +/- 2 mo vs Standard 8 +/- 3 mos., P = .7), number of physical therapy visits (9 +/- 2 vs 10 +/- 2, P = .81) or duration of treatment (7.2 +/- 0.8 wk vs 7.0 +/- 0.6 wk, P = .69). Improvements in all dependent variables were greater for the Eccentric Group versus the Standard Treatment Group (percent improvement reported): DASH 76% vs 13%, P = .01; VAS 81% vs 22%, P = .002, tenderness 71% vs 5%, P = .003; strength (wrist and middle finger extension combined) 79% vs 15%, P = .011. DISCUSSION: All outcome measures for chronic lateral epicondylosis were markedly improved with the addition of an eccentric wrist extensor exercise to standard physical therapy. This novel exercise, using an inexpensive rubber bar, provides a practical means of adding isolated eccentric training to the treatment of chronic lateral epicondylosis. PMID- 20579908 TI - Treatment of traumatic posterior sternoclavicular dislocations. AB - BACKGROUND: Traumatic posterior sternoclavicular joint injuries are rare, but complications are common and include brachial plexus and vascular injury, esophageal rupture, and death. MATERIALS AND METHODS: The records of 21 patients treated at our institution for a posterior sternoclavicular injury were reviewed. All patients underwent a trial of closed reduction, which was effective in 8 patients (group I). The remaining 13 patients were treated with open reduction and sternoclavicular joint reconstruction (group II). RESULTS: Closed reduction was more likely to be successful (P < .05) in dislocations treated within 10 days of injury. Patients were evaluated by use of the University of California, Los Angeles rating scale. Overall, 18 of 21 patients were graded as good or excellent. Patients treated with either open or closed reduction as their definitive management compared favorably in terms of ratings for pain, strength, and motion. CONCLUSION: Our experience suggests that closed reduction compares favorably with open reduction. Of patients treated, 38% required only closed reduction as their definitive treatment. In this series early closed reduction was successful and obviated the risks of surgery. Patients who in whom closed reduction failed obtained good results with operative treatment aimed at reconstruction of the costoclavicular ligaments. PMID- 20579909 TI - Effect of chronic vagal nerve stimulation on interictal epileptiform discharges. AB - We evaluated the effect of vagus nerve stimulation (VNS) on interictal epileptiform discharges (IEDs) in 32 epileptic patients (18 females; 14 males) with an average age of 42.2+/-11.4 years, all of whom had been suffering from epilepsy for an average of 29.2+/-14.5 years. All of the patients had received VNS for 5 years. The first EEG was performed prior to the initiation of stimulation; the second EEG was performed at the 5-year follow-up visit. The duration of each EEG was 30 min. We compared these two EEGs in terms of the number of IEDs present in each patient and correlated them to other variables. The average total number of IEDs during EEG and the total number of seconds in which IEDs were present decreased significantly after 5 years of stimulation from 97.3+/-106.9 resp. 80.6+/-86.1 to 49.4+/-94.0 resp. 37.8+/-65.0. Although there was no positive correlation between the reduction of IEDs and the percent of seizure reduction, we found a greater decrease of IEDs in patients who responded to VNS in comparison to those who did not. The decrease of IEDs was more pronounced in patients suffering from temporal lobe epilepsy than in patients suffering from extratemporal epilepsy. No other significant correlations were found. VNS reduced IEDs in patients chronically simulated for epilepsy. The reduction of IEDs was greater in patients who responded to VNS and in patients suffering from temporal lobe epilepsy. PMID- 20579910 TI - The variability of the Achilles tendon insertion: a cadaveric examination. AB - Pathology associated with the Achilles tendon is a common problem, particularly at the site of insertion. A better understanding of the anatomy in this area would assist in developing and fine-tuning treatment options. A cadaveric examination was conducted using 60 human lower extremities (40 cadavers) to determine the location for the terminal insertion site of the Achilles tendon on the posterior aspect of the calcaneus. The average age of the specimens was 67.8 years (range, 43-98 years). Three different investigators examined each specimen, and a consensus as to the site of termination of the Achilles tendon was made. Upon inspection, 55% (22/40) of the limbs had the Achilles tendon inserting on the superior 1/3 aspect of the calcaneus, 40% (16/40) of the limbs inserted on the middle 1/3, and 5% (2/40) of the limbs inserted on the inferior 1/3. The distribution of the insertion was statistically different from random (P = .000371). Further, 8% (3/40) of the specimens revealed a partially contiguous relationship between the Achilles tendon and the plantar fascia. This correlated with the younger specimens (P < .0001). This study provides a better understanding of the anatomical relationship between the Achilles tendon, the calcaneus, and the plantar fascia. PMID- 20579911 TI - The direct tensor solution and higher-order acquisition schemes for generalized diffusion tensor imaging. AB - Both in diffusion tensor imaging (DTI) and in generalized diffusion tensor imaging (GDTI) the relation between the diffusion tensor and the measured apparent diffusion coefficients is given by a tensorial equation, which needs to be inverted in order to solve the diffusion tensor. The traditional way to do this does not preserve the tensorial structure of the equation, which we consider a weakness in the method. For a physically correct measurement procedure, the condition number of the acquisition scheme, which is a determinant of the noise behavior, needs to be rotationally invariant. The method which traditionally is used to find such schemes, however, is cumbersome and mathematically unsatisfactory. This is considered a second weakness, closely connected to the first. In this paper we present an alternative inversion of the diffusion tensor equation, which does preserve the tensor form, for arbitrary order, and which is named the direct tensor solution (DTS). The DTS is derived under the assumption that the apparent diffusion coefficient in any direction is known, i.e. in the infinite acquisition scheme. Whenever the DTS is valid for a given finite acquisition scheme and for a given order, the condition number is rotationally invariant. The DTS provides a compact, algebraic procedure to check this rotational invariance. We also present a method to construct acquisition schemes, for which the DTS is valid for the measurement of higher-order diffusion tensors. Furthermore, the DTS leads to other mathematical insights, such as tensorial relationships between diffusion tensors of different orders, and a more general understanding of the Platonic Variance Method, which we published before. PMID- 20579912 TI - Analysis and comparison of 2D fingerprints: insights into database screening performance using eight fingerprint methods. AB - Virtual screening is a widely used strategy in modern drug discovery and 2D fingerprint similarity is an important tool that has been successfully applied to retrieve active compounds from large datasets. However, it is not always straightforward to select an appropriate fingerprint method and associated settings for a given problem. Here, we applied eight different fingerprint methods, as implemented in the new cheminformatics package Canvas, on a well validated dataset covering five targets. The fingerprint methods include Linear, Dendritic, Radial, MACCS, MOLPRINT2D, Pairwise, Triplet, and Torsion. We find that most fingerprints have similar retrieval rates on average; however, each has special characteristics that distinguish its performance on different query molecules and ligand sets. For example, some fingerprints exhibit a significant ligand size dependency whereas others are more robust with respect to variations in the query or active compounds. In cases where little information is known about the active ligands, MOLPRINT2D fingerprints produce the highest average retrieval actives. When multiple queries are available, we find that a fingerprint averaged over all query molecules is generally superior to fingerprints derived from single queries. Finally, a complementarity metric is proposed to determine which fingerprint methods can be combined to improve screening results. PMID- 20579913 TI - Dose calculation algorithm of fast fine-heterogeneity correction for heavy charged particle radiotherapy. AB - This work addresses computing techniques for dose calculations in treatment planning with proton and ion beams, based on an efficient kernel-convolution method referred to as grid-dose spreading (GDS) and accurate heterogeneity correction method referred to as Gaussian beam splitting. The original GDS algorithm suffered from distortion of dose distribution for beams tilted with respect to the dose-grid axes. Use of intermediate grids normal to the beam field has solved the beam-tilting distortion. Interplay of arrangement between beams and grids was found as another intrinsic source of artifact. Inclusion of rectangular-kernel convolution in beam transport, to share the beam contribution among the nearest grids in a regulatory manner, has solved the interplay problem. This algorithmic framework was applied to a tilted proton pencil beam and a broad carbon-ion beam. In these cases, while the elementary pencil beams individually split into several tens, the calculation time increased only by several times with the GDS algorithm. The GDS and beam-splitting methods will complementarily enable accurate and efficient dose calculations for radiotherapy with protons and ions. PMID- 20579914 TI - Prolonged paradoxical response to anti-tuberculous treatment after infliximab. AB - A 56-year-old woman with ankylosing spondylitis, treated for 3 months with infliximab, developed miliary tuberculosis with mediastinal lymphadenopathies and brain and splenic lesions. After initial improvement under anti-tuberculous therapy, she suffered an unexpectedly prolonged paradoxical worsening with several episodes of lymphadenopathy, including life-threatening ones, over a period of more than 14 months of follow-up. The outcome was favorable as a result of corticosteroid and surgical treatments. This phenomenon reflects a paradoxical reaction precipitated by infliximab withdrawal. PMID- 20579915 TI - Brucellosis infection presenting with cholestasis. AB - Brucellosis is a relatively common disease in the Mediterranean area and may present with prolonged fever without focus, however it remains an important diagnostic challenge to most pediatricians. We report the case of a 10-year-old male patient who presented with fever without a focus of 10-day duration, hepatomegaly, ascites, a small elevation in transaminases and acute-phase reactants indicating cholestasis, leukopenia, and thrombocytopenia. Imaging tests showed many small, rounded, hypodense focal lesions in the liver and spleen. After eliminating a wide range of diseases, positive results for the Rose Bengal test and indirect immunofluorescence assay for Brucella melitensis made it possible to establish a diagnosis of hepatosplenic brucellosis. A review of the family history revealed direct contact with farm animals. The patient made good progress on treatment with doxycycline and streptomycin, with complete resolution of both clinical symptoms and imaging signs. The prevalence of brucellosis is gradually increasing, mainly due to migratory movements. It should always be eliminated as a source of unknown fever in endemic areas and should also be taken into account in other geographical areas where it is not common whenever a patient presents with prolonged fever and unspecific symptoms. Standard therapy is highly effective, even in relapse cases, and early diagnosis leads to a rapid recovery and favorable outcome. The unusual presentation in the case reported here reminds us that it is possible to encounter a Brucella infection in a case of fever without a focus, irrespective of the existence of a clear epidemiological history, which is very often omitted by the family. All differential diagnostic protocols for fever without a focus should include a diagnostic test for Brucella in order to achieve early detection of the disease and initiate therapy promptly. PMID- 20579916 TI - Effect of type 2 diabetes on plasma kallikrein activity after physical exercise and its relationship to post-exercise hypotension. AB - AIM: The present study was undertaken to determine the effects of type 2 diabetes (T2D) on plasma kallikrein activity (PKA) and postexercise hypotension (PEH). METHODS: Ten T2D patients (age: 53.6+/-1.3 years; body mass index: 30.6+/ 1.0kg/m(2); resting blood glucose: 157.8+/-40.2mgdL(-1)) and 10 non-diabetic (ND) volunteers (age: 47.5+/-1.0 years; body mass index: 28.3+/-0.9kg/m(2); resting blood glucose: 91.2+/-10.5mgdL(-1)) underwent two experimental sessions, consisting of 20min of rest plus 20min of exercise (EXE) at an intensity corresponding to 90% of their lactate threshold (90LT) and a non-exercise control (CON) session. Blood pressure (BP; Microlife BP 3AC1-1 monitor) and PKA were measured during rest and every 15min for 135min of the postexercise recovery period (RP). RESULTS: During the RP, the ND individuals presented with PEH at 30, 45 and 120min (P<0.05) while, in the T2D patients, PEH was not observed at any time. PKA increased at 15min postexercise in the ND (P<0.05), but not in the T2D patients. CONCLUSION: T2D individuals have a lower PKA response to exercise, which probably suppresses its hypotensive effect, thus reinforcing the possible role of PKA on PEH. PMID- 20579917 TI - Decreasing postprandial C-peptide levels over time are not associated with long term use of sulphonylurea: an observational study. AB - AIM: The present study aimed to describe changes over 10 years in HbA(1c) and beta-cell function, as assessed by postprandial C-peptide (PP-CPT) and C peptide/glucose (PP-CPT/glucose) ratio, and to investigate whether treatment with sulphonylurea (SU) exerts a deleterious effect on beta-cell function. METHODS: During 1997-1998, HbA(1c), PP-CPT and PP glucose were measured in 462 patients. Ten years later, 171 of the 341 patients who were still alive were followed-up. RESULTS: HbA(1c) decreased from 7.41 to 6.96% (P=0.002) as treatments were intensified. There was a decrease in both PP-CPT (P<0.001) and PP-CPT/glucose ratio (P=0.063). A multivariable-regression model was used to evaluate the effects on beta-cell function changes, using the following variables as effect modifiers: gender; age; BMI; diabetes duration; baseline PP-CPT/glucose ratio; HbA(1c); GAD-antibody class; and SU treatment (continuously, periodically, never). Baseline PP-CPT/glucose ratio was the most important variable (R(2)=45%; P<0.001) for explaining variations in beta-cell function. An increase in HbA(1c) was associated with a decrease in beta-cell function, and beta-cell function remained unchanged if glycaemic control was improved. Long-term treatment with SU had no effect on long-term changes in beta-cell function (R(2)=0.1%; P=0.894). CONCLUSION: Both HbA(1c) and beta-cell function decreased over 10 years with SU treatment, but such treatment was not associated with a pronounced decline in beta-cell function. These results, however, need to be interpreted with caution, as this was an observational study. Nevertheless, the present study findings do not support the notion that SU, as used in clinical practice, is harmful to beta cell function. PMID- 20579918 TI - [Predictive value of uterine artery velocity waveforms in monitoring of pregnancies with high obstetrical risk antiphospholipid syndrome: the Rouen experience]. AB - OBJECTIVES: Anti-phospholipid syndrome (APLS) and obstetrical complications have been associated for years. The purpose of this study was to define a high obstetrical risk subpopulation of APLS and search predictive criteria of complications likely to improve monitoring of pregnancy. PATIENTS AND METHODS: We conducted a retrospective study at the CHU of Rouen between 1998 and January 2008. Pregnancies were included for patients with APLS according to the criteria of Sydney without repeated miscarriages item. RESULTS: The study involved 20 pregnancies from eight patients. Fourteen pregnancies gave birth to living children or 70 %, 28.6 % were complicated with pre-eclampsia, 50 % of haemolysis elevated liver enzymes low platelets (HELLP) syndrome associated with a 28.6 % stunting and 42 % of premature birth. Patients received treatment involving aspirin and heparin. The obstetrical prognosis was significantly poorer in the subgroup with APLS notch bilateral persistent middle of the term of birth of 35.5 versus 28 weeks of gestation, and median birth weight of 950 g versus 2780 g (p<0.05). DISCUSSION AND CONCLUSION: Patients were selected according to the more specific criteria of APLS (thrombosis and fetal loss) and a history of severe obstetrical complications. In some series, these complications play a major role; in others, they are unsignificant. Rate, in this study, is high (47 %) and the presence of bilateral notch seems to be an excellent predictive marker of vascular complications in this population. PMID- 20579919 TI - [Fertility after endometrial osseous metaplasia elective hysteroscopic resection]. AB - OBJECTIVES: The endometrial osseous metaplasia is a rare disease which is characterized by the presence of osseous tissue in endometrium. It is often diagnosed in women with secondary infertility. The main objective of this work is to evaluate fertility after elective resection of osteoid metaplasia endometrial lesions by operative hysteroscopy in infertile women. PATIENTS AND METHOD: Retrospective and descriptive series of 7 cases observed in the Woman and Child department, CHU Jean-Verdier. The 7 women were in reproductive age, of African origin, with secondary infertility after abortions concerning 6 out of the 7 patients. RESULTS: In all cases, endovaginal pelvic ultrasound has raised endometrial calcification, and diagnostic hysteroscopy highlighted endometrial osteoid metaplasia. The operative hysteroscopic procedure consisted of elective diathermic resection to handle endometrial insertion of bone chips. A second diagnostic hysteroscopy was systematically done. It showed no recurrence. Six of the 7 patients began pregnancy, 3 spontaneously and 3 after IVF/ICSI in the first year following the hysteroscopic treatment. The evolution of pregnancies has been marked by 2 normal deliveries, 1 spontaneous miscarriage and then an ectopic pregnancy in one patient, 1 growth retardation intrauterine requiring caesarean at 38 SA, 1 HELLP syndrome in a twin pregnancy requiring ceasarean at 27 SA followed normal labor at term and 1 pregnancy lost sight. DISCUSSION AND CONCLUSION: Hysteroscopic elective resection seems to be the treatment of choice with a good prognosis on subsequent fertility. PMID- 20579920 TI - [Neurotrophins and pain in endometriosis]. AB - OBJECTIVES: To evaluate the expression of five members of the neurotrophins family in ovarian endometriotic cyst (endometrioma) (OMA), compared to eutopic endometrium (EE) and to examine the correlation between the levels of induction and the pain intensity. PATIENTS AND METHODS: Twelve Caucasian women in luteal phase, operated for painful stage IV endometriosis were assigned to 2 groups according to a total Visual Analog Scale (tVAS) score above 15 or below 10. tVAS takes into account all VAS scores for dysmenorrhea, deep dyspareunia, non cyclic chronic pelvic pain, gastrointestinal and lower urinary symptoms. Samples of OMA and EE were processed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for NGF, BDNF, NT-3, NT-4/5 and NTRK2 mRNA expression. Expression levels in OMA were compared to those in EE on one hand and between two groups of 6 mild painful and 6 highly painful patients on the other. RESULTS: All neurotrophins were significantly higher expressed in OMA than in EE, in particular NGF and BDNF (induction ratios: 20.6 and 9.7, respectively). In contrast, no correlation was observed between induction ratios and pain intensity. CONCLUSION AND DISCUSSION: This is the first study reporting an over expression of all neurotrophins in endometriosis, as only NGF was previously documented. It confirms the central role of this family in the genesis and modulation of pain in endometriosis. Anti-neurotrophin selective therapy might be a promising way of analgesia in the future. PMID- 20579921 TI - [Surgical treatment of tubo-ovarian abscess occurring in deep endometriosis]. AB - Tubo-ovarian abscesses are likely to occur in women suffering from deep endometriosis. The aim of surgical management of tubo-ovarian abscesses is the laparoscopic drainage, while deep endometriosis resection should be delayed. Laparoscopic procedure carried out in emergency does not attempt at the excision of deep endometriotic lesions, and must avoid the choice of the laparoconversion, in order to avoid further changes in the pelvic anatomy rendering more difficult a curative surgery. We report six cases of patients presenting tubo-ovarian abscesses arising on deep endometriosis, and we discuss the choice of the 2-step surgical management. In four cases, deep endometriosis resection has been performed by laparoscopic route few months after the drainage of abscess and provided macroscopically complete excision of the disease. PMID- 20579922 TI - [Why not creating a N4 stage in breast cancer?]. PMID- 20579923 TI - [Clinicopathological and genomics predictors of response to neoadjuvant chemotherapy in breast cancer]. AB - Breast cancer is a frequent and heterogeneous disease. The choice of systemic treatments such as chemotherapy is based on predicting factors of response that did not much evolve. Preoperative chemotherapy provides an opportunity to directly assess tumor response to therapy. Predictors based on mathematical models could optimize those treatments. To go on this way, three different concepts have been developed to predict the preoperative chemotherapy complete response. Predictors based on clinical and pathological variables are specific of a tumor. They combine into mathematical models variables that have been previously identified as predicting the preoperative chemotherapy complete response. Predictors based on gene expression profile have been developed from groups of patients who received preoperative chemotherapy. They integrate multigene information to predict the tumor behaviour in front of several cytotoxic agents. Those predictors developed for each type of drug characterize the genetic chemoresistance of a tumor. In the same time, predictors of chemosensitivity developed from cell lines of diverse human cancer appeared. The authors established a genetic profile involved into chemoresistance and extrapolated the drug sensitivity for another type of cancer which was not represented, as breast cancer. All those predictors seem interesting but evolution of patients' characteristics and treatments induces a perpetual reassessment to optimize our predictive abilities. PMID- 20579924 TI - [Non-invasive prenatal diagnosis: a tool for the future? Which consequences for our practices?]. PMID- 20579925 TI - An efficient one-pot synthesis of new 2-imino-1,3-thiazolidin-4-ones under ultrasonic conditions. AB - A convenient one-pot protocol was developed for the synthesis of 2-imino-1,3 thiazolidin-4-ones by the reaction of amines, isocyanates, aldehydes, and chloroform in the presence of sodium hydroxide under ultrasonic conditions in high yields (75-91%) and shorter reaction times (12-15 min). PMID- 20579926 TI - Synthesis of stabilizer-free gold nanoparticles by pulse sonoelectrochemical method. AB - In this paper, stabilizer-free gold nanoparticles (Au NPs) were synthesized by a facile pulse sonoelectrochemical method in the absence of stabilizer. The size and shape of the Au NPs can be controlled by adjusting current density, reaction time and the pH value of the precursor solution. The morphology and structure of the Au NPs were characterized by transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), UV-visible spectra (UV-vis), energy-dispersive X-ray (EDX) and X-ray diffraction (XRD). The pH value has a great effect on the size and dispersion of the obtained Au NPs. The Au NPs could further used as substrate for fabrication of HRP biosensor which exhibited excellent biocatalytical activity with high sensitivity and rapid response. This method provides a facile route for the synthesis of stabilizer-free Au NPs. Since the preparation process do not need the addition of any surfactants/capping agent, the resulting Au NPs are suitable for the applications in fields of biology and catalysis. PMID- 20579927 TI - Synthesis and characterization of nano-bentonite by sonochemical method. AB - Nano-bentonite with novel nano-wire morphology has been fabricated by a sonochemical method in different ultrasound powers, times and concentrations. The nano-bentonite was characterized by X-ray fluorescence analysis (XRF), X-ray powder diffraction (XRD), thermal gravimetry analysis (TGA), differential thermal analysis (DTA) and infrared spectroscopy. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that using ultrasound irradiation led to a bentonite nanostructure. The surface area of the bulk and nano-bentonite was determined by BET. PMID- 20579928 TI - Visualization of acoustic cavitation effects on suspended calcite crystals. AB - The acoustic cavitation (42,080 Hz, 7.1 W cm(-2) or 17 W) effects on suspended calcite crystals, sized between 5 and 50 MUm, have been visualized for the first time using high speed photography. High speed recordings with a duration of 1 s containing up to 300,000 frames per second, revealed the effect of cluster and streamer cavitation on several calcite crystals. Cavitation clusters, evolved from cavitation inception and collapse, caused attrition, disruption of aggregates and deagglomeration, whereas streamer cavitation was observed to cause deagglomeration only. Cavitation on the surface gave the crystals momentum. However, it is shown that breakage of accelerated crystals by interparticle collisions is unrealistic because of their small sizes and low velocities. Crystals that were accelerated by bubble expansion, subsequently experienced a deceleration much stronger than expected from drag forces, upon bubble collapse. Experiments with pre-dried crystals seemed to support the current theory on bubble nucleation through the presence of pre-existing gas pockets. However, experiments with fully wetted crystals also showed the nucleation of bubbles on the crystal surface. Although microjet impingement on the crystal surface could not be directly visualized with high speed photography, scanning electron microscopy (SEM) analysis of irradiated calcite seeds showed deep circular indentations. It was suggested that these indentations might be caused by shockwave induced jet impingement. Furthermore, the appearance of voluminous fragments with large planes of fracture indicated that acoustic cavitation can also cause the breakage of single crystal structures. PMID- 20579929 TI - Head movement kinematics during rapid aiming task performance in healthy and neck pain participants: the importance of optimal task difficulty. AB - BACKGROUND: Head repositioning tasks have been used in different experimental and clinical contexts but have yet to offer insight as to the task performance strategy. The purpose of this study was to explore the kinematics from a head aiming task that encompasses a Fitts' task in neck pain patients and healthy control subjects. METHODS: Chronic neck pain patients and healthy individuals were compared in a head aiming task. Participants were asked to move their head as quickly, and precisely as possible to a target under 4 different experimental conditions. Dependent variables included movement time, movement time variability, acceleration phase duration, deceleration phase duration and absolute positioning error. RESULTS: The chronic neck pain patients, when compared to healthy participants showed a significant increase in movement time and deceleration phase duration for the small target/large movement amplitude condition. No group difference was observed for movement time variability, acceleration phase duration and absolute positioning errors. CONCLUSIONS: Decreased motor performance was observed in chronic neck pain patients during the most challenging cervical pointing task condition. These results may imply that in order for a performance based outcome measure to yield observable differences conditions that meet or exceed the optimum challenge point of the population tested should be employed. PMID- 20579930 TI - Manifold modeling for brain population analysis. AB - This paper describes a method for building efficient representations of large sets of brain images. Our hypothesis is that the space spanned by a set of brain images can be captured, to a close approximation, by a low-dimensional, nonlinear manifold. This paper presents a method to learn such a low-dimensional manifold from a given data set. The manifold model is generative-brain images can be constructed from a relatively small set of parameters, and new brain images can be projected onto the manifold. This allows to quantify the geometric accuracy of the manifold approximation in terms of projection distance. The manifold coordinates induce a Euclidean coordinate system on the population data that can be used to perform statistical analysis of the population. We evaluate the proposed method on the OASIS and ADNI brain databases of head MR images in two ways. First, the geometric fit of the method is qualitatively and quantitatively evaluated. Second, the ability of the brain manifold model to explain clinical measures is analyzed by linear regression in the manifold coordinate space. The regression models show that the manifold model is a statistically significant descriptor of clinical parameters. PMID- 20579931 TI - Respiratory motion compensation by model-based catheter tracking during EP procedures. AB - In many cases, radio-frequency catheter ablation of the pulmonary veins attached to the left atrium still involves fluoroscopic image guidance. Two-dimensional X ray navigation may also take advantage of overlay images derived from static pre operative 3D volumetric data to add anatomical details otherwise not visible under X-ray. Unfortunately, respiratory motion may impair the utility of static overlay images for catheter navigation. We developed a novel approach for image based 3D motion estimation and compensation as a solution to this problem. It is based on 3D catheter tracking which, in turn, relies on 2D/3D registration. To this end, a bi-plane C-arm system is used to take X-ray images of a special circumferential mapping catheter from two directions. In the first step of the method, a 3D model of the device is reconstructed. Three-dimensional respiratory motion at the site of ablation is then estimated by tracking the reconstructed catheter model in 3D based on bi-plane fluoroscopy. Phantom data and clinical data were used to assess model-based catheter tracking. Our phantom experiments yielded an average 2D tracking error of 1.4mm and an average 3D tracking error of 1.1mm. Our evaluation of clinical data sets comprised 469 bi-plane fluoroscopy frames (938 monoplane fluoroscopy frames). We observed an average 2D tracking error of 1.0 + or - 0.4mm and an average 3D tracking error of 0.8 + or - 0.5mm. These results demonstrate that model-based motion-compensation based on 2D/3D registration is both feasible and accurate. PMID- 20579932 TI - Causes and consequences of mind perception. AB - Perceiving others' minds is a crucial component of social life. People do not, however, always ascribe minds to other people, and sometimes ascribe minds to non people (e.g. God, gadgets). This article reviews when mind perception occurs, when it does not, and why mind perception is important. Causes of mind perception stem both from the perceiver and perceived, and include the need for social connection (perceiver) and a similarity to oneself (perceived). Mind perception also has profound consequences for both the perceiver and perceived. Ascribing mind confers an entity moral rights and also makes its actions meaningful. Understanding the causes and consequences of mind perception can explain when this most social of cognitive skills will be used, and why it matters. PMID- 20579933 TI - The peculiarities of flagella in parasitic protozoa. PMID- 20579934 TI - Characterization of a sandfly fever Sicilian virus isolated during a sandfly fever epidemic in Turkey. AB - BACKGROUND: Phleboviruses cause sandfly fever but isolates are rare. OBJECTIVES: To analyse samples from concurrent outbreaks of suspected sandfly fever in the Mediterranean provinces of Adana, Izmir and the central province of Ankara, Turkey. STUDY DESIGN: Samples from acute cases were analysed by immunofluorescence assay (IFA). Virus isolation was attempted and pyrosequencing performed. RESULTS: In IFA 38% of 106 samples tested scored IgM positive for sandfly fever Sicillian virus (SFSV), 12% for SFSV/sandfly fever Cyprus Virus (SFCV) and only 4% for SFCV. A sandfly fever Sicilian type virus designated sandfly fever Turkey virus (SFTV) was isolated. The S-segment sequence of SFTV had a homology of 98% to that of SFCV. The M-segment sequence showed a 91.1% homology to the only SFSV sequence available. The L-segment sequence showed a homology of 58% and 60.3% to Toscana virus and Rift Valley Fever virus sequences, a partial 201nt sequence showed 95.5% homology to the SFSV Sabin strain. CONCLUSION: A new phlebovirus related to sandfly fever Sicilian virus, SFTV was isolated and characterized from acute patient material. The sandfly fever Sicilian virus activity seems to be changing in Turkey. Entomological studies are needed. PMID- 20579935 TI - Dual oxidase in mucosal immunity and host-microbe homeostasis. AB - Mucosal epithelia are in direct contact with microbes, which range from beneficial symbionts to pathogens. Accordingly, hosts must have a conflicting strategy to combat pathogens efficiently while tolerating symbionts. Recent progress has revealed that dual oxidase (DUOX) plays a key role in mucosal immunity in organisms that range from flies to humans. Information from the genetic model of Drosophila has advanced our understanding of the regulatory mechanism of DUOX and its role in mucosal immunity. Further investigations of DUOX regulation in response to symbiotic or non-symbiotic bacteria and the in vivo consequences in host physiology will give a novel insight into the microbe controlling system of the mucosa. PMID- 20579936 TI - Trafficking properties of plasmacytoid dendritic cells in health and disease. AB - Plasmacytoid dendritic cells (PDCs) represent a subset of circulating leukocytes characterized by the ability to release high levels of type I interferon (IFN). Under homeostatic conditions PDCs are confined to primary and secondary lymphoid organs. This is consistent with the restricted profile of functional chemotactic receptors expressed by circulating PDCs (i.e. CXCR4 and ChemR23). Accumulation of PDCs in non-lymphoid tissue is, however, observed in certain autoimmune diseases, allergic reactions and tumors. Indeed, PDCs are now considered to be involved in the pathogenesis of diseases characterized by a type I IFN-signature and are considered as a promising target for new intervention strategies. Here, current knowledge of the molecular mechanisms involved in the recruitment of PDCs under homeostatic and pathological conditions are summarized. PMID- 20579937 TI - Physical activity in Arab women in Southern California. AB - BACKGROUND: The limited research of Arab women suggests that most are sedentary. Given the known health benefits of physical activity suggests that the study of physical activity of women in Southern California where the climate favors year round outdoor activities is warranted. AIMS: To describe Arab women's cardiovascular risk factors (CVD): physical activity levels, self-efficacy, and determinants of physical inactivity and their preferences for physical activity programs. METHODS: This cross-sectional design used the International Physical Activity Questionnaire (IPAQ), Exercise Self-Efficacy Scale, Choose to Move Questionnaire, and "How America Measures Up" Questionnaire. RESULTS: The mean age of the 180 women was 37.6 (+/-12.9). Most (91.1%) had >=high school education, 68.9% were married, and 24.4% were below poverty level. CVD risk factors were: hypertension 20.6%; hyperlipidemia 21.1%; diabetes 10%; and excess weight in 60%. Their self-efficacy scores were 39.2 (+/-18.2); and 46.2% were sedentary. A logistic regressions analysis found statistically significant determinant(s) for physical inactivity performance were low self-efficacy score and "not being born in the U.S." CONCLUSIONS: These young Arab women are considerably physically inactive and overweight. The findings from our study can guide culturally relevant health promotion programs in Arab women who have unique needs and preferences. PMID- 20579938 TI - Randomized comparison of long-term desmopressin and alarm treatment for bedwetting. AB - OBJECTIVE: To compare the efficacy of long-term primary nocturnal enuresis (PNE) treatment using desmopressin versus enuresis alarm. MATERIALS AND METHODS: A 6 month randomized trial was performed with patients from 29 enuresis clinics: 251 patients >= 5 years in age with severe PNE (mean 5.5-5.6 wet nights/week) were randomized to desmopressin (0.2-0.4 mg daily) or alarm. Efficacy was assessed by percentage reduction in mean number of wet nights/week; patients achieving dryness, mean initial duration of sleep and compliance were evaluated. Efficacy analyses were performed using the intent-to-treat population (all patients) and excluding patients who withdrew; 12-month follow-up data were collected. RESULTS: Data could not be evaluated for the 32% of alarm patients and 7% of desmopressin patients who withdrew early. In intent-to-treat analyses, a similar proportion of patients across groups showed a >= 50% reduction in wet nights/week (desmopressin: 37.5%, alarm: 32.2%) and achieved dryness (desmopressin: 32%, alarm: 37%). Compliance was higher with desmopressin: 95-98% of patients took >75% of tablets; 50-78% used alarm >75% of nights. Initial sleep duration was 1.02 h longer at the end of treatment with desmopressin (95% CI: 0.045, 1.99). CONCLUSION: Desmopressin and alarm demonstrated comparable efficacy in the treatment of PNE. Withdrawal from the alarm group was high, indicating the importance of considering family motivation before selecting treatment, for optimal outcome. PMID- 20579939 TI - Polymicrogyria without epilepsy by aberrantly migrating inhibitory interneurons. PMID- 20579940 TI - Assessing pain in older people with persistent pain: the NRS is valid but only provides part of the picture. AB - This study examined the assessment of pain intensity and pain distress with the Numerical Rating Scale (NRS) in elderly patients (age > 60 years) with persistent pain. A consecutive sample of 800 elderly patients were categorized by age into 3 groups: 61 to 70 years (n = 366), 71 to 80 years (n = 308), and 81 years and over (n = 126). Participants completed 3 Numerical Rating Scales assessing current pain intensity, and both the usual level of pain and average pain distress in the preceding week. The failure rate for scale completion was low for all scales for all age groups, but was significantly higher in the oldest group compared to the youngest group for the scales assessing current pain intensity and average pain distress in the preceding week. The NRS was shown to be a reliable and valid measure of pain intensity and pain distress in all these age groups. Distress related to pain appeared to be specific to the pain experience and was only weakly related to more generalized affective distress. These findings confirm that measures of pain intensity and pain distress, like the NRS, capture only part of the pain experience in older patients and should be supplemented by other measures in the assessment process. PERSPECTIVE: This article confirms the utility of the Numerical Rating Scale (NRS) as a measure of pain intensity and pain distress in elderly patients with persistent pain. The use of a large sample increases confidence in the psychometric soundness of the NRS with this population. PMID- 20579942 TI - Wound retraction system for isobaric laparoendoscopic single-site surgery to treat adnexal tumors: pilot study. AB - Transumbilical laparoendoscopic single-site (LESS) surgery is a recent advancement in minimally invasive surgery. However, this procedure usually requires a specialized multichannel port for introducing the laparoscope and instruments under pneumoperitoneum. In an isobaric procedure, a wound retractor alone can conveniently be used for transumbilical single-site access. Fourteen isobaric LESS adnexal surgeries including 1 emergency procedure with adnexal torsion were performed using multiple instruments inserted through the wound retractor. No extraumbilical incisions or conversion to standard multiple-port laparoscopic surgery were required. Port-related complications were not noted, and the cosmetic results were excellent. A wound retractor offers safe and reliable access for isobaric LESS adnexal surgery as an alternative to the current specialized port systems. PMID- 20579943 TI - Narrow-band imaging in diagnosis of endometrial cancer and hyperplasia: a new option? AB - STUDY OBJECTIVE: To estimate whether the use of narrow-band imaging (NBI) hysteroscopy increases concordance between visual identification and a histologic diagnosis of endometrial cancer and hyperplasia. DESIGN: Prospective study (Canadian Task Force classification: II-2). SETTING: Department of obstetrics and gynecology, University of Eastern Piedmont, Novara, Italy. PATIENTS: 209 consecutive patients with abnormal uterine bleeding. INTERVENTIONS: White-light hysteroscopy and NBI hysteroscopy followed by direct biopsy. MEASUREMENTS AND MAIN RESULTS: The sensitivity and specificity of conventional hysteroscopy in predicting a diagnosis of cancer and hyperplasia were, respectively, 84.21% (95% confidence interval [CI], 79.27-89.15) and 99.47% (95% CI, 98.49-100.0), and 64.86% (95% CI, 58.39-71.34) and 98.77% (95% CI, 97.27-100.0), and of NBI hysteroscopy were 94.74% (95% CI, 91.71-97.76) and 97.89% (95% CI, 95.95-99.84), and 78.38% (95% CI, 72.8-83.96) and 97.67% (95% CI, 96.63-99.72). The concordance of conventional and NBI hysteroscopy with the histopathologic findings (measured using the Cohen kappa) was, respectively, 88.80% (95% CI, 86.2%-96.3%) and 91.78% (95% CI, 89.6%-98.2%), a difference of 2.98% (95% CI, 0-9) in favor of NBI. CONCLUSION: Narrow-band imaging hysteroscopy can accurately predict a histologic diagnosis of endometrial cancer or hyperplasia. PMID- 20579941 TI - Integrative genomic profiling of human prostate cancer. AB - Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator NCOA2 as an oncogene in approximately 11% of tumors. Additionally, the androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates FOXP1, RYBP, and SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource. PMID- 20579944 TI - Changes in stature, weight, and nutritional status with tourism-based economic development in the Yucatan. AB - Over the past 40 years, tourism-based economic development has transformed social and economic conditions in the Yucatan Peninsula, Mexico. We address how these changes have influenced anthropometric indicators of growth and nutritional status in Yalcoba, a Mayan farming community involved in the circular migration of labor in the tourist economy. Data are presented on stature and weight for children measured in 1938 in the Yucatan Peninsula and from 1987 to 1998 in the Mayan community of Yalcoba. In addition, stature, weight and BMI are presented for adults in Yalcoba based on clinic records. Childhood stature varied little between 1938 and 1987. Between 1987 and 1998 average male child statures increased by 2.6cm and female child statures increased by 2.7cm. Yet, 65% of children were short for their ages. Between 1987 and 1998, average child weight increased by 1.8kg. Child BMIs were similar to US reference values and 13% were considered to be above average for weight. Forty percent of adult males and 64% of females were overweight or obese. The anthropometric data from Yalcoba suggest a pattern of stunted children growing into overweight adults. This pattern is found elsewhere in the Yucatan and in much of the developing world where populations have experienced a nutrition transition toward western diets and reduced physical activity levels. PMID- 20579945 TI - Community well-being and growth status of indigenous school children in rural Oaxaca, southern Mexico. AB - OBJECTIVE: To evaluate the relationship between community well-being based on an index of marginalization and growth status of indigenous rural school children in Oaxaca. METHODS: Heights and weights of a cross-sectional sample of 11,454 children, 6-14 years, from schools for indigenous rural children (escuelas albergue) in 158 municipios in Oaxaca were measured in 2007. Tertiles of an index of marginalization were used to classify the 158 municipios into three categories of community well-being: lowest (highest marginalization), low, and moderate (lowest marginalization). Multivariate analysis of covariance, controlling for age, relative isolation and population size, was used to compare body size of children by category of community well-being. Contributions of marginalization, isolation and population size to variation in body size were estimated with sex specific linear regression. RESULTS: Children from municipios lowest in well being were shorter and lighter than children from municipios low and moderate in well-being. Marginalization and relative isolation accounted for 23% (boys) and 21% (girls) of the variance in height and for 21% of the variance in weight of girls. Marginalization was the predictor of weight in boys (23%). CONCLUSION: Community well-being was reflected in the growth status of rural indigenous school children. Compromised growth status was consistent with poor health and nutritional conditions that were and are characteristic of rural areas in the state of Oaxaca. PMID- 20579946 TI - Cigarette smoking and appendectomy: effect on clinical course of diverticulosis. AB - AIM: To investigate the effect of appendectomy and cigarette smoking on the clinical course of diverticulosis. MATERIALS AND METHODS: A retrospective case control study of 207 consecutive patients (45.8% male mean age 64.0 years), 150 with asymptomatic diverticulosis, and 57 with acute diverticulitis. Diagnosis of diverticulosis was defined on the basis of clinical and colonoscopic criteria, diverticulitis was defined by means of clinical, colonoscopic and computerised tomography criteria. Logistic regression function was used to define the relationship between the dependent variable (diverticulitis) and several covariates: sex, age, body mass index, smoking habit, and history of appendectomy. RESULTS: According to the final model, the risk of diverticulitis was 4.94-fold higher (95% confidence interval: 1.98-12.37) in patients with a history of appendectomy with emergency resection, compared to patients not submitted to appendectomy or with a history of elective resection (P < 0.001); and 2.79-fold higher (95% confidence interval: 1.30-5.96) in smokers than in non smokers (P = 0.008). The effects of the two determinants were found to be independent, thus the cumulative risk of diverticulitis was 13.78-fold higher for smokers with a history of emergency surgical treatment. CONCLUSION: Smoking and emergency appendectomy are important predictive factors for the clinical course of diverticulosis. PMID- 20579947 TI - Prophylactic cross-face nerve flap for muscle protection prior to facial palsy. AB - The facial muscles of a 28-year-old woman with left acoustic neuroma were successfully protected with a vascularised cross-face nerve flap using a vascularised lateral femoral cutaneous nerve along with a perforator of the lateral circumflex femoral system. It was transferred as a vascularised cross face nerve flap to bridge a 15-cm-long defect between the bilateral buccal branches. Three months after the nerve flap transfer, the total tumour including the facial nerve was resected. Postoperatively, rapid nerve sprouting through the nerve flap and excellent facial reanimation were obtained 3-6 months after resection. This method is a one-stage reconstruction procedure, has minimal donor site morbidity and results in strong postoperative muscle contraction. To our knowledge, this is the first report on a prophylactic cross-face nerve flap technique for the protection of facial muscles before facial nerve transection, and also the usefulness of vascularised lateral femoral cutaneous nerve flap. PMID- 20579948 TI - Breast augmentation: Part II--Adverse capsular contracture. AB - Although adverse capsular contracture (ACC) following breast augmentation remains an enigmatic phenomenon, significant progress has been made in diminishing its occurrence during the previous surgical generation. Given the rising global frequency of breast augmentation, however, ACC is likely to be with us for the foreseeable future and an understanding of its nature, and particularly prevention, will continue to be of foremost importance as breast augmentation undergoes a paradigm shift from anti-contracture to aesthetic result as the key outcome measure. Whilst clinical research has hitherto been the mainstay of investigation, providing both understanding and practical guidance, further improvements may derive from new developments in the fields of immunology and molecular biology: convergence of these complementary avenues may eventually yield a non-surgical treatment for ACC. This review presents a summary of our extant knowledge, providing evidence where it exists and a consensus view where it does not. It aims at providing a sound comprehension of the underlying aetiopathology that has provoked the measures seen to date and guides selection of the appropriate therapeutic strategy, which will be expanded in a future review. PMID- 20579949 TI - Breast reconstruction: a quantitative assessment of the quality of information available to patients. PMID- 20579951 TI - [Amyloidosis of the external auditory canal]. AB - Amyloidosis involving the external ear is extremely rare. We present the case of a 76-year-old man who referred unilateral otorrhea and hypoacusis of six months' duration. The external auditory canal (EAC) was narrowed by a subcutaneous nodule. After its extirpation, unilateral localised amyloidosis of the EAC was diagnosed. In these rare cases, it is crucial to rule out systemic amyloidosis. PMID- 20579950 TI - Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women? AB - INTRODUCTION: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. METHODS: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. RESULTS: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=-0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=-0.32, p=0.0076), and increasing body mass index (BMI) (r=-0.31, p=<0.0001; r=0.39, p=<0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p=0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend=0.43), aPAI-1 (p=0.78), or resistin (p=0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p>0.05). The lack of association with risk may be due to measurement error of the laboratory assays. DISCUSSION: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk. PMID- 20579952 TI - [Post-tonsillectomy haemorrhage--do coagulation tests and coagulopathy history have predictive value?]. AB - OBJECTIVES: Determining post-tonsillectomy haemorrhage (PTH) risk factors is crucial for preventing it. The aim of the study was to analyse results of coagulation tests and preoperative family and medical history of coagulation disorders in order to establish if they have predictive value for PTH. METHODS: In 222 patients aged 15-60 years, values of APTT (Activated Partial Thromboplastin Time), prothrombin/INR ratio and platelet count as well as medical history were analysed and 15 episodes of secondary PTH occurred. This includes 3 of 9 (33.3%) patients with medical history of proneness to bruises after minor trauma and in all (4) patients who declared both relevant medical history of proneness to bruise formation after minor trauma and proneness to prolonged bleeding after injury. RESULTS: Five individuals had elevated APTT values and proneness to bruise formation after minor trauma, and other six patients had elevated APTT values, relevant history of frequent epistaxis and family coagulation disorders. In none of these patients PTH occurred. There was one episode of primary and no secondary PTH in 15 patients with values of APTT elevated < or =10% of the normal value. No PTH occurred in 6 individuals with APTT elevated by >10% of the normal value. Haemorrhage rate correlated with APTT results, proneness to bruise formation and to bleeding after injuries. Values of specificity of recurrent epistaxis, history of bruises after minor trauma and prolonged bleeding after injury were significant. CONCLUSIONS: In healthy adults, coagulation tests results are irrelevant for the course of tonsillectomy and postoperative bleeding event. Personal medical history is important in predicting PTH. PMID- 20579953 TI - The effect of tumor-associated protein RCAS1 gene silencing on blood pressure and urinary protein excretion in pregnant mouse: a pilot study. AB - OBJECTIVE: The level of tumor-associated receptor-binding cancer antigen that is expressed on SiSo cells (RCAS1) is decreased significantly in preeclamptic pregnancies. We hypothesized that RCAS1 protein gene silencing might affect blood pressure and proteinuria in pregnant mice. STUDY DESIGN: On postcoital day 7.5, pregnant imprinting control region mice were subjected to the transfer of small interfering RNA (siRNA) against RCAS1 protein into the uterine cavity with the use of a hemagglutinating virus Japan envelope. Scramble siRNA was used as a negative control. Blood pressure and urine albumin/creatinine measurements were performed. The effect of the transferred siRNA was examined in uterine samples on postcoital day 8.5 with the use of Western blotting and immunohistochemistry analyses. RESULTS: In the RCAS1 siRNA group, blood pressure significantly raised on postcoital days 9.5, 10.5, 11.5, and 15.5, whereas urine albumin/creatinine ratio was significantly increased on postcoital day 9.5 CONCLUSION: Our results suggest the importance of RCAS1 protein in the pathophysiologic condition of preeclampsia. PMID- 20579954 TI - Survey of obstetric and gynecologic hospitalists and laborists. AB - OBJECTIVE: The objective of the study was to obtain descriptive information about obstetricians/gynecologists who currently are practicing as hospitalists or laborists. STUDY DESIGN: A survey was emailed to all actively practicing member Fellows of the American College of Obstetricians and Gynecologists in April 2009. A second emailing of the survey was sent in May 2009. RESULTS: Obstetrician/gynecologist hospitalists and laborists are significantly younger than the rest of the obstetrician/gynecologist sample by age and years in residency and have a high rate of career satisfaction. There was a great deal of variation in work schedules and compensation of the respondents. CONCLUSION: We analyzed the rapidly growing hospitalist/laborist model of care within the obstetrician/gynecologist specialty. The laborists and hospitalists model provides an alternative type of practice for obstetricians/gynecologists, and it is associated with high career satisfaction. It is important that we continue to monitor the needs of this burgeoning field of clinical practice. PMID- 20579956 TI - Idiopathic recurrent pregnancy loss recurs at similar gestational ages. AB - OBJECTIVE: To determine whether a correlation exists between gestational ages of idiopathic recurrent pregnancy loss (iRPL). STUDY DESIGN: Cohort of women with iRPL who had an initial loss (qualifying pregnancy [QP]) with precise documentation of gestational age. Outcomes in the immediate next pregnancy (index pregnancy [IP]) were compared between preembryonic (group I), embryonic (group II), or fetal (group III) losses in the QP. RESULTS: Three hundred thirty-four women met inclusion criteria. In their IP, group I had 41% preembryonic, 28% embryonic, and 10% fetal losses. Group II had 14% preembryonic, 53% embryonic, and 9% fetal losses. Group III had 19% preembryonic, 23% embroyonic, and 29% fetal loses. Correlation coefficient for type of loss among the QPs and IPs was 0.14, P = .009. CONCLUSIONS: Women with iRPL tend to have losses recur in the same gestational age period. Causes for RPL may be gestational age specific and should guide further investigations into causes. PMID- 20579958 TI - The risk of adverse pregnancy outcomes is increased in preeclamptic women who smoke compared with nonpreeclamptic women who do not smoke. AB - OBJECTIVE: Maternal smoking and preeclampsia independently increase the risk of adverse pregnancy outcomes; however, smoking decreases the risk of preeclampsia. We sought to estimate the risk of adverse pregnancy outcomes among preeclamptic women who smoke and hypothesized that this risk would be increased, compared with nonpreeclamptic women who smoke or preeclamptic women who do not smoke. STUDY DESIGN: With the use of the Niday Perinatal Database and multiple logistic regressions, we estimated the risk of adverse pregnancy outcomes in nonpreeclamptic women who smoke, preeclamptic women who do not smoke, and preeclamptic women who smoke in relation to nonpreeclamptic women who do not smoke. RESULTS: The incidence of adverse pregnancy outcomes was more than twice as high among preeclamptic women who smoke as among nonpreeclamptic women who do not smoke. The following data were observed: small-for-gestational-age infant (odds ratio [OR], 3.40; 95% CI, 2.27-4.89), preterm birth (OR, 5.77; 95% CI, 4.50 7.35), very preterm birth (OR, 5.44; 95% CI, 3.51-8.11), abruption (OR, 6.16; 95% CI, 3.05-11.01), Apgar <4 at 5 minutes (OR, 3.11; 95% CI, 1.48-5.72), and stillbirth (OR, 3.39; 95% CI, 1.33-6.99). CONCLUSION: Smoking decreases the risk of preeclampsia, but smokers with preeclampsia have an increased risk for adverse pregnancy outcomes. PMID- 20579957 TI - Gestational age at previous preterm birth does not affect cerclage efficacy. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of earliest previous spontaneous preterm birth (SPTB) gestational age on cervical length, pregnancy duration, and ultrasound-indicated cerclage efficacy in a subsequent gestation. STUDY DESIGN: Planned secondary analysis of the National Institute of Child Health and Human Development-trial of cerclage for cervical length of <25 mm. Women with at least 1 previous SPTB between 17-33 weeks 6 days of gestation underwent serial vaginal ultrasound screening between 16 and 23 weeks 6 days of gestation; cervical length at qualifying randomization evaluation was used. RESULTS: We observed a significant correlation (P = .0008) between previous SPTB gestational age and qualifying cervical length. In a linear regression model that was controlled for cervical length and cerclage, neither previous SPTB gestational age nor the interaction between cerclage and previous birth gestational age was significant predictor of subsequent birth gestational age. CONCLUSION: Although there is an association between previous SPTB gestational age and cervical length in women with a mid-trimester cervical length of <25 mm, there does not appear to be a disproportionate benefit of cerclage in women with earlier previous SPTB. PMID- 20579955 TI - The effect of plurality and obesity on betamethasone concentrations in women at risk for preterm delivery. AB - OBJECTIVE: Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect medication distribution volume. We evaluated whether maternal or neonatal cord betamethasone concentrations differed in twin gestations or obese patients. STUDY DESIGN: Participants receiving betamethasone in a randomized controlled trial of weekly ACS were identified. We analyzed maternal delivery and cord serum betamethasone concentrations comparing singletons with twins and obese (BMI > or =30 kg/m(2)) with nonobese women. RESULTS: Fifty-five maternal and 45 cord blood samples were available. Unadjusted median maternal serum concentrations appeared paradoxically higher in both twin gestations and the obese. However, after controlling for confounders, there were no differences in betamethasone concentrations in maternal serum or cord blood between singletons and twins (P = .61 vs P = .14) or nonobese and obese women (P = .67 vs .12). CONCLUSION: Maternal and umbilical cord blood serum betamethasone concentrations are not different in twin gestations or obese women. PMID- 20579959 TI - Contemporary management of monochorionic diamniotic twins: outcomes and delivery recommendations revisited. AB - OBJECTIVE: We sought to investigate outcomes of contemporaneously managed monochorionic diamniotic (MCDA) twins, stratified by pregnancy complication. STUDY DESIGN: Four hundred eighteen MCDA pregnancies from 2001 through 2008 were retrospectively reviewed. RESULTS: There were 236 ongoing pregnancies at 24 weeks' gestation. The likelihood of progressing from 24 weeks to 2 live births was 98.7% in uncomplicated pregnancies, 89.7% with twin-twin transfusion syndrome, and 100% with growth discordance, increasing at 32 weeks to 99.5%, 93.8%, and 100%, respectively. The relative risk (RR) of birth <32 weeks was significantly greater in twin-twin transfusion syndrome (RR, 4.1; 95% confidence interval, 2.7-6.1) and growth discordant (RR, 2.1; 95% confidence interval, 1.8 3.8) pregnancies than in uncomplicated pregnancies (P < .0001). CONCLUSION: This represents one of the largest cohorts of MCDA twins. The risk of third-trimester fetal loss was low. The likelihood of both intrauterine fetal demise and preterm birth were greater in complicated pregnancies. In the absence of a clinical indication for delivery, these data do not support elective preterm delivery for prevention of intrauterine fetal demise in uncomplicated MCDA twins. PMID- 20579960 TI - Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 5-year outcome from the randomized EMMY trial. AB - OBJECTIVE: The purpose of this study was to compare clinical outcome and health related quality of life (HRQOL) 5 years after uterine artery embolization (UAE) or hysterectomy in the treatment of menorrhagia caused by uterine fibroids. STUDY DESIGN: Patients with symptomatic uterine fibroids who were eligible for hysterectomy were assigned randomly 1:1 to hysterectomy or UAE. Endpoints after 5 years were reintervention rates, menorrhagia, and HRQOL measures that were assessed by validated questionnaires. RESULTS: Patients were assigned randomly to UAE (n = 88) or hysterectomy (n = 89). Five years after treatment 23 of 81 UAE patients (28.4%) had undergone a hysterectomy because of insufficient improvement of complaints (24.7% after successful UAE). HRQOL measures improved significantly and remained stable until the 5-year follow-up evaluation, with no differences between the groups. UAE had a positive effect both on urinary and defecation function. CONCLUSION: UAE is a well-established alternative to hysterectomy about which patients should be counseled. PMID- 20579961 TI - Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. AB - OBJECTIVE: To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients. STUDY DESIGN: Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival. CONCLUSION: Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients. PMID- 20579962 TI - To the editors. PMID- 20579965 TI - Time for improved standards for studies of home birth. PMID- 20579964 TI - Pregnancy outcome after in utero exposure to colchicine. AB - OBJECTIVE: We sought to examine the fetal safety of colchicine. STUDY DESIGN: This was a prospective observational comparative cohort study regarding colchicine exposure during pregnancy including contacts to 2 Teratology Information Services in Israel from 1994 through 2006. RESULTS: In all, 238 colchicine-exposed pregnancies (97.0% first trimester) and 964 pregnancies with nonteratogenic exposure were followed up. Treatment indications were: familial Mediterranean fever (87.3%), Behcet disease (7.5%), or other (5.2%). The rate of major congenital anomalies was comparable between the groups (10/221 [4.5%] vs 35/908 [3.9%]; P = .648). There were no cytogenetic anomalies in the colchicine group. The median gestational age at delivery was earlier (39 [38-40] vs 40 [38 41] weeks; P < .001), the rate of preterm deliveries was higher (32/214 [15.0%] vs 51/867 [5.9%]; P < .001), and the median birthweight was lower (3000 [2688 3300] vs 3300 [2900-3600] g; P < .001) in the colchicine group. CONCLUSION: The present study suggests that colchicine does not appear to be a major human teratogen, and, probably, has no cytogenetic effect. PMID- 20579967 TI - Dynamic modulation of cytoskeleton during in vitro maturation in human oocytes. AB - OBJECTIVE: To investigate the role of cytoskeleton in several important dynamic events during in vitro maturation of human oocytes. STUDY DESIGN: Human germinal vesicle stage oocytes were divided randomly into control and study groups. After cultured for 24 hours, chromatin state and position, spindle formation and migration, cortical granules, and mitochondria distribution were evaluated. RESULTS: In colchicine group, spindles did not form. Cortical granules migrated to the cortex but mitochondria maintained the peripheral distribution pattern in most of the oocytes. In cytochalasin B group, the migration of spindle and chromosomes to the cortex was prohibited. Microfilaments disruption influenced cortical granules migration but not redistribution of mitochondria. CONCLUSION: Meiosis progression could not go beyond metaphase I stage when microtubule or microfilament polymerization was prohibited in human oocytes. The migration of cortical granules to the cortex and redistribution of mitochondria to the inner cytoplasm were mediated by microfilaments and microtubules, respectively. PMID- 20579968 TI - Causality in the systems era of pediatric ophthalmology: the Buddha's smile. AB - PURPOSE: To identify the inherent complexities in assigning causation in the evolving systems era of pediatric ophthalmology. DESIGN: Philosophical analysis of causality as it pertains to understanding the pathogenesis of pediatric strabismus and nystagmus. METHODS: Review of general philosophical problems and profession-related differences in assigning causality as they apply to current controversies in pediatric ophthalmology. RESULTS: Medicine is evolving into a systems era based on a complex network of interacting components including internal systems, gene expression, behavioral factors, and environmental factors. In this context, any definition of cause (epidemiologic, mechanical, physiologic, environmental, genetic, epigenetic, etc.) becomes a function of one's reference point. Thus, as medical science becomes more precise, causality seems to recede. Most current controversies in pediatric ophthalmology are reducible to simple questions of cause and effect. Strabismus and nystagmus often develop without apparent cause, providing a formidable challenge to deciphering disease pathogenesis and assigning causality. In these conditions, assigning causation is impeded by a tendency to confuse links and correlations with cause and effect, an inherent tendency to conflate form and function, the use of terminology that transposes cause and effect, and by our tendency to think linearly about problems that are fundamentally circular. CONCLUSIONS: Our tendency to think linearly creates a self-referential system that influences our understanding of cause and effect. Neural activity is characterized by feedback loops and bidirectionality. Understanding neurodevelopmental strabismus and nystagmus requires a dynamic, circular view of causality. PMID- 20579969 TI - Visfatin and gallstone disease. PMID- 20579970 TI - Preoperative platelet-lymphocyte ratio in resected pancreatic ductal carcinoma: is it meaningful? PMID- 20579971 TI - Effect of prescribed sleep surfaces on back pain and sleep quality in patients diagnosed with low back and shoulder pain. AB - The purpose of this study was to assess sleep quality and comfort of participants diagnosed with low back pain and stiffness following sleep on individually prescribed mattresses based on dominant sleeping positions. Subjects consisted of 27 patients (females, n=14; males, n=13; age 44.8 yrs +/- SD 14.6, weight 174 lb. +/- SD 39.6, height 68.3 in. +/- SD 3.7) referred by chiropractic physicians for the study. For the baseline (pretest) data subjects recorded back and shoulder discomfort, sleep quality and comfort by visual analog scales (VAS) for 21 days while sleeping in their own beds. Subsequently, participants' beds were replaced by medium-firm mattresses specifically layered with foam and latex based on the participants' reported prominent sleeping position and they again rated their sleep comfort and quality daily for the following 12 weeks. Analysis yielded significant differences between pre- and post means for all variables and for back pain, we found significant (p<0.01) differences between the first posttest mean and weeks 4 and weeks 8-12, thus indicating progressive improvement in both back pain and stiffness while sleeping on the new mattresses. Additionally, the number of days per week of experiencing poor sleep and physical discomfort decreased significantly. It was concluded that sleep surfaces are related to sleep discomfort and that is indeed possible to reduce pain and discomfort and to increase sleep quality in those with chronic back pain by replacing mattresses based on sleeping position. PMID- 20579972 TI - T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine. AB - BACKGROUND: Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. METHODS: We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl) N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self administration on a progressive ratio (PR) schedule, and nicotine- and cue induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. RESULTS: TTA-A2 dose dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. CONCLUSIONS: These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. PMID- 20579973 TI - Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients. AB - BACKGROUND: Cocaine users not seeking treatment have increased regional brain mu opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown. METHODS: We determined whether regional brain mOR binding before treatment correlates with outcome and compared it with standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine abstinence reinforcement, whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography with [11C]]-carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment; and 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology. RESULTS: Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sublobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use. CONCLUSIONS: Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction. PMID- 20579974 TI - Decreased prefrontal cortical volume associated with increased bedtime cortisol in traumatized youth. AB - BACKGROUND: The purpose of this study was to investigate prefrontal cortex (PFC) volumes in youth with posttraumatic stress symptoms (PTSS) and explore the relationship between cortisol secretion and PFC volumes. METHODS: Total brain tissue volumes, segmented areas of the PFC, and diurnal cortisol secretion were examined in a sample of 33 youth aged 10 to 16 years. Cerebral volumes were available for 45 subjects (30 PTSS and 15 control subjects). RESULTS: Youth with PTSS had significantly decreased total brain tissue and total cerebral gray volumes in comparison with healthy control subjects. While controlling for total cerebral gray volume, the PTSS group demonstrated decreased left ventral and left inferior prefrontal gray volumes. A significant negative association was found between prebedtime cortisol levels and left ventral PFC gray volumes for the full sample. CONCLUSIONS: Findings suggest associations between posttraumatic stress and PFC neurodevelopment. Findings also suggest a link between PFC development and cortisol secretion. PMID- 20579976 TI - Chemical synthesis of beta-D-psicofuranosyl disaccharides. AB - Disaccharides composed of a beta-D-psicofuranosyl unit were prepared by the glycosylation reaction of monosaccharide acceptors including three 2,3,4,6-tetra O-protected hexopyranoses with a D-psicofuranosyl benzyl phthalate derivative (4). A beta-D-psicofuranosidic bond was formed by the TMSOTf-promoted reaction with high selectivity. Removal of the O-protecting groups from the resulting alpha-D-hexopyranosyl beta-D-psicofuranosides furnished the first chemical synthesis of alpha-D-gluco-, alpha-D-galacto-, and alpha-D-mannopyranosyl beta-D psicofuranosides. The common beta-D-psicofuranosyl donor 4 was derived efficiently from D-psicose in five steps. PMID- 20579975 TI - gamma-Aminobutyric acid-type A receptor deficits cause hypothalamic-pituitary adrenal axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. AB - BACKGROUND: The gamma-aminobutyric acid (GABA) Type A receptor deficits that are induced by global or forebrain-specific heterozygous inactivation of the gamma2 subunit gene in mouse embryos result in behavior indicative of trait anxiety and depressive states. By contrast, a comparable deficit that is delayed to adolescence is without these behavioral consequences. Here we characterized gamma2-deficient mice with respect to hypothalamic-pituitary-adrenal (HPA) axis abnormalities and antidepressant drug responses. METHODS: We analyzed the behavioral responses of gamma2(+/-) mice to desipramine and fluoxetine in novelty suppressed feeding, forced swim, tail suspension, and sucrose consumption tests as well as GABA(A) receptor deficit- and antidepressant drug treatment-induced alterations in serum corticosterone. RESULTS: Baseline corticosterone concentrations in adult gamma2-deficient mice were elevated independent of whether the genetic lesion was induced during embryogenesis or delayed to adolescence. However, the manifestation of anxious-depressive behavior in different gamma2-deficient mouse lines was correlated with early onset HPA axis hyperactivity during postnatal development. Chronic but not subchronic treatment of gamma2(+/-) mice with fluoxetine or desipramine normalized anxiety-like behavior in the novelty suppressed feeding test. Moreover, desipramine had antidepressant-like effects in that it normalized HPA axis function and depression-related behavior of gamma2(+/-) mice in the forced swim, tail suspension, and sucrose consumption tests. By contrast, fluoxetine was ineffective as an antidepressant and failed to normalize HPA axis function. CONCLUSIONS: Developmental deficits in GABAergic inhibition in the forebrain cause behavioral and endocrine abnormalities and selective antidepressant drug responsiveness indicative of anxious-depressive disorders such as melancholic depression, which are frequently characterized by HPA axis hyperactivity and greater efficacy of desipramine versus fluoxetine. PMID- 20579977 TI - Enzymatic synthesis of alpha-glucosyl-timosaponin BII catalyzed by the extremely thermophilic enzyme: Toruzyme 3.0L. AB - Timosaponin BII (BII), a steroidal saponin showing potential anti-dementia activity, was converted into its glucosylation derivatives by Toruzyme 3.0L. Nine products with different degrees of glucosylation were purified and their structures were elucidated on the basis of (13)C NMR, HR-ESI-MS, and FAB-MS spectra data. The active enzyme in Toruzyme 3.0L was purified to electrophoretic homogeneity by tracking BII-glycosylase activity and was identified as Cyclodextrin-glycosyltransferase (CGTase, EC 2.4.1.19) by ESI-Q-TOF MS/MS. In this work, we found that the active enzyme catalyzed the synthesis of alpha-(1- >4)-linked glucosyl-BII when dextrin instead of an expensive activated sugar was used as the donor and showed a high thermal tolerance with the most favorable enzymatic activity at 100 degrees C. In addition, we also found that the alpha amylases and CGTase, that is, GH13 family enzymes, all exhibited similar activities, which were able to catalyze glucosylation in steroidal saponins. But other kinds of amylases, such as gamma-amylase (GH15 family), had no such activity under the same reaction conditions. PMID- 20579978 TI - Synthesis and antioxidant activity of a novel class of 4,6-O-protected O glycosides and their utility in disaccharide synthesis. AB - BF(3).Et(2)O-catalysed O-glycosylation of 1,2,3-tri-O-acetyl-4,6-O-butylidene- and ethylidene-beta-d-glucopyranose with different aliphatic and aromatic alcohols proceeds for the most part with complete retention of anomeric configuration. Antioxidant activity of O-glycosides shows significant inhibition (IC(50) approximately 77%). 1,3-Dipolar cycloaddition of terminal alkyne derivatives of O-glycosides with glycosyl azide results in disaccharides. PMID- 20579979 TI - Toll-like receptor (TLR) expression on CD4+ and CD8+ T-cells in patients chronically infected with hepatitis C virus. AB - Toll-like receptor (TLR) expression on T-cells and the signalling pathways that lead to the production of cytokines may limit antigen-specific T-cell responses. Here, expression of TLR and retinoic acid inducible gene I (RIG-I) on T-cells were evaluated in patients chronically infected with hepatitis C virus (HCV), before and during pegylated interferon-alpha and ribavirin therapy. Expression of TLR2,3,4,7,9 and retinoic acid inducible gene (RIG)-I on different CD4(+) and CD8(+) T-cell sub-populations (naive: CD45RA(+)CD57(-); central memory: T(CM) CD45RA(-)CD57(-); effector memory: T(EM) CD45RA(-)CD57(+) and terminally differentiated effector memory: T(EMRA) CD45RA(+)CD57(+)) were measured by flow cytometry. TLR7, TLR9 and RIG-I expression on CD4(+) T-cells and RIG-I expression on CD8(+) T-cells was higher in patients than healthy controls. Therapy increased expression of TLR2, TLR4 and TLR9 and this was observed for all T-cell sub populations. Evaluation of TLR expression at baseline did not identify patients able to achieve sustained virological response following therapy. PMID- 20579980 TI - [Multimodal (fast-track) rehabilitation in elective colorectal surgery: evaluation of the learning curve with 300 patients]. AB - INTRODUCTION: The aim of this paper is to assess the learning curve on compliance to the application of a multimodal rehabilitation program (MMRP) protocol and patient recovery after elective colorectal surgery. MATERIAL AND METHODS: A comparative prospective study of 3 consecutive cohorts of 100 patients (P1, P2 and P3) who had colonic or rectal surgery. The same MMRP protocol was applied in all cases. Compliance to the protocol, tolerance to the diet and walking have been analysed. The percentages of early hospital discharges have also been compared. RESULTS: Compliance gradually improved, reaching statistical significance between P1 and P3. Starting the diet on day 1 post-surgery was 52% vs 86% (p=0.0001) and the removal of drips was 21% vs 40% (p=0.005). This difference remained during days 2 and 3. Tolerance to the diet on day 1 (P1: 34% vs. P3: 66%; p=0.0001) and walking on day 2 (P1: 41% vs. P3: 68%; p=0.0002) were also better in the third period. No differences in morbidity were found between the three periods. The percentage of hospital discharges on day 3 P1: 1% vs. P3: 15%; p=0.0003), day 4 (P1: 12% vs. P3: 32%; p=0.001) and day 5 (P1: 30% vs. P3: 50%; p=0.002) was higher in the third period. CONCLUSIONS: The compliance to the protocol and the results of applying the MMRP improved significantly with the greater experience of the professionals involved. PMID- 20579981 TI - On the nature of hand-action representations evoked during written sentence comprehension. AB - We examine the nature of motor representations evoked during comprehension of written sentences describing hand actions. We distinguish between two kinds of hand actions: a functional action, applied when using the object for its intended purpose, and a volumetric action, applied when picking up or holding the object. In Experiment 1, initial activation of both action representations was followed by selection of the functional action, regardless of sentence context. Experiment 2 showed that when the sentence was followed by a picture of the object, clear context-specific effects on evoked action representations were obtained. Experiment 3 established that when a picture of an object was presented alone, the time course of both functional and volumetric actions was the same. These results provide evidence that representations of object-related hand actions are evoked as part of sentence processing. In addition, we discuss the conditions that elicit context-specific evocation of motor representations. PMID- 20579982 TI - Reply to commentary "Time series analysis on the health effects of temperature: two areas for future research" by Gasparrini and Armstrong. PMID- 20579984 TI - Focus on...the role of PPARgamma in adipogenesis. PMID- 20579983 TI - Defending the end zone: studying the players involved in protecting chromosome ends. AB - The linear nature of eukaryotic chromosomes leaves natural DNA ends susceptible to triggering DNA damage responses. Telomeres are specialized nucleoprotein structures that comprise the "end zone" of chromosomes. Besides having specialized sequences and structures, there are six resident proteins at telomeres that play prominent roles in protecting chromosome ends. In this review, we discuss this team of proteins, termed shelterin, and how it is involved in regulating DNA damage signaling, repair and replication at telomeres. PMID- 20579985 TI - Involvement of the Hipk family in regulation of eyeball size, lens formation and retinal morphogenesis. AB - Members of the homeodomain-interacting protein kinase (HIPK) family are involved in various intracellular regulatory mechanisms. The present study focused on clarifying the functions of HIPK family members in ocular organization during late embryogenesis. HIPK1 and HIPK2 were expressed in the inner retina during late embryogenesis. Hipk1(+/-)Hipk2(-/-) mice had a greater frequency of small eyes with a lens deficiency and abnormally laminated and thickened retinas than did wild-type littermates. These data indicate that Hipk1 and Hipk2 are involved in regulation of eye size, lens formation and retinal lamination during late embryogenesis. PMID- 20579986 TI - Difference between serum beta-human chorionic gonadotropin levels in pregnancies after in vitro maturation and in vitro fertilization treatments. AB - OBJECTIVE: To compare beta-hCG levels measured as the first pregnancy test in women who conceived after in vitro maturation (IVM) or IVF. DESIGN: Retrospective matched cohort analysis. SETTING: University-based medical center. PATIENT(S): Women treated with IVM or IVF. INTERVENTION(S): We studied the first serum beta hCG levels in 104 pregnant women who were successfully treated with IVM and in another 104 women with IVF treatment. Blood samplings for beta-hCG were drawn on day 12-15 after ET. The two groups were matched by age, order of pregnancy, and day of blood sampling. MAIN OUTCOME MEASURE(S): First beta-hCG levels. RESULT(S): Serum beta-hCG levels on days 12 to 13 after ET of IVM viable singleton pregnancies were significantly higher than those of IVF pregnancies (343.2+/-48.4 vs. 264.0+/-29.2 IU/L, 95% confidence interval [CI] 22-229). Similarly, beta-hCG levels on days 14 to 15 after ET of IVM viable singleton pregnancies were higher than those of IVF pregnancies (350.1+/-126.4 vs. 284.4+/-30.2 IU/L). Similar trends were found in beta-hCG levels on days 12 to 13 after ET of twin viable pregnancies (IVM, 682.1+/-97.7 vs. IVF, 434.5+/-41.8 IU/L; 95% CI 44-662). Grouped linear regression with covariance analysis showed a significant difference between IVM and IVF regression lines. CONCLUSION(S): The first serum beta-hCG levels in pregnancies after IVM are consistently higher than those after IVF treatment. More studies are needed to elucidate these findings. PMID- 20579987 TI - Intravenous albumin administration for the prevention of severe ovarian hyperstimulation syndrome: a systematic review and metaanalysis. AB - OBJECTIVE: To reappraise the currently available evidence, providing the answer to the following question: does intravenous albumin administration reduce the risk of severe ovarian hyperstimulation syndrome (OHSS) occurrence following ovarian stimulation with gonadotrophins and GnRH analogues for IVF in high-risk patients? DESIGN: Systematic review and metaanalysis. SETTING: University-based hospital. INTERVENTION(S): Intravenous albumin administration in high-risk patients for prevention of severe OHSS occurrence. MAIN OUTCOME MEASURE(S): Severe OHSS occurrence. RESULT(S): Eight eligible randomized controlled trials were identified (n=1,199 patients) that offered data for statistical pooling. No statistically significant difference in the occurrence of severe OHSS in patients who received intravenous albumin (n=595) and those who did not (n=604; odds ratio [OR], 0.80; 95% confidence interval [CI], 0.52-1.22) was detected. Moreover, no statistically significant differences were present regarding the probability of pregnancy (OR, 0.83; 95% CI, 0.64-1.07) and first trimester pregnancy loss (OR, 1.44; 95% CI, 0.73-2.85) between patients who received intravenous albumin and those who did not. CONCLUSION(S): Based on the currently best available evidence, intravenous albumin administration in high-risk patients does not appear to reduce the occurrence of severe OHSS. This finding should be considered when implementing strategies for severe OHSS prevention. PMID- 20579988 TI - Insurance mandates, embryo transfer, outcomes--the link is tenuous. AB - To examine the relationship between state insurance mandate status and the number of embryos transferred in assisted reproductive technology cycles, we conducted a retrospective analysis of clinics reporting to the publicly available national Society for Assisted Reproductive Technology registry. We found that clinics in states with comprehensive mandates transferred between 0.210 and 0.288 fewer embryos per cycle depending upon patient age, and were more likely to transfer fewer embryos than recommended for older women; however, the relationship between state mandate status and clinic birth and multiple birth rates varied by age group. PMID- 20579989 TI - Luteal phase progesterone increases live birth rate after frozen embryo transfer. AB - OBJECTIVE: To see if progesterone support has a beneficial effect on live birth rate after frozen embryo transfer in natural cycles. DESIGN: Prospective randomized controlled trial. SETTING: University-based hospital. SUBJECT(S): Four hundred thirty-five women undergoing embryo transfer in natural cycles. INTERVENTION(S): The women received either vaginal progesterone, 400 mg twice a day from the day of embryo transfer in natural cycles, or no progesterone support. MAIN OUTCOME MEASURE(S): Live birth rate, biochemical pregnancy rate, pregnancy rate, and spontaneous abortion rate. RESULT(S): Live birth rate were significantly greater in women receiving vaginal progesterone as luteal phase support after frozen-thawed embryo transfer in natural cycles compared with those who did not take progesterone. There were no differences in biochemical pregnancy rate, pregnancy rate, or spontaneous abortion rate. CONCLUSION(S): Progesterone supplementation improves live birth rate after embryo transfer in natural cycles. PMID- 20579990 TI - The role of MSP I CYP1A1 gene polymorphism in the development of uterine fibroids. AB - The cytochrome P-450 1A1 (CYPA1A) gene plays an important role in the metabolization of estrogen and is therefore a candidate marker for fibroids. In a case-control study, we were unable to demonstrate any association between MSP I CYP1A1 polymorphism and the risk of leiomyoma in Brazilian women. PMID- 20579991 TI - Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction. AB - BACKGROUND: A 6F endoscopic biliary self-expanding metal stent (SEMS) has been newly introduced for intended simultaneous side-by-side bilateral deployment in hilar malignant obstruction. OBJECTIVE: To report our initial experience with the Zilver 635 biliary SEMS. DESIGN: Retrospective chart review. SETTING: Tertiary referral medical center. PATIENTS: Sixteen consecutive malignant hilar biliary obstruction patients. INTERVENTIONS: Endoscopic palliative treatment of malignant biliary obstruction with the Zilver 635 SEMS from December 2008 to January 2010. MAIN OUTCOME MEASUREMENTS: Technical/functional success rates, early complications (within 30 days of stent placement), early/late stent occlusion, and biliary reintervention rates. RESULTS: A total of 49 Zilver SEMSs were placed in 16 patients (mean age 61 years, 6 men) for Bismuth type II (n = 4), III (n = 5), and IV (n = 7) lesions. Twelve had cholangiocarcinoma, 2 had metastatic colon cancer, 1 had lung cancer, and 1 had pancreatic cancer. The technical success rate was 100%. Side-by-side simultaneous bilateral stent deployment was required and was achieved successfully in 10 cases. Additional transpapillary stents were placed for potential future biliary access. The 30-day mortality rate was 0%. There were 1 early (6%) and 3 late (19%) stent occlusions. Successful overall biliary drainage was 75%. LIMITATIONS: Small sample size, uncontrolled retrospective study. CONCLUSIONS: Malignant hilar biliary obstruction endoscopic palliation with the Zilver 635 SEMS offers acceptable initial feasibility, safety, and efficacy profiles. The current design facilitates smaller bile duct negotiation and more precise intrahepatic placement. Expanding available lengths would allow transpapillary bridged bilateral SEMS placement for future reobstructed biliary access. Further long-term studies are required for comparative outcomes with other current SEMS technology. PMID- 20579992 TI - EUS-FNA of extracolonic lesions by using the forward-viewing linear echoendoscope. PMID- 20579993 TI - Minimum staffing requirements for the performance of GI endoscopy. AB - This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines. PMID- 20579994 TI - Split dosing of bowel preparations for colonoscopy: an analysis of its efficacy, safety, and tolerability. PMID- 20579995 TI - Massive lower GI bleed from an endoscopically inevident rectal varices: diagnosis and management by EUS (with videos). PMID- 20579996 TI - The role of acute total hip arthroplasty in the treatment of acetabular fractures. PMID- 20579997 TI - Evaluation of laparoscopic management of gynecologic emergencies by residents. AB - OBJECTIVE: To evaluate the feasibility of laparoscopic management of women with gynecologic emergencies by the residents and the chief resident in an organized resident training program. METHODS: A retrospective study of patients with gynecologic emergencies who underwent laparoscopic surgery between January 1, 1999, and May 31, 2006 was done. RESULTS: For the 369 patients included, the mean operative time of 74+/-31.35 minutes was significantly increased by advanced patient age (P<0.001), pelvic inflammatory disease with or without tubo-ovarian abscess (PID+/-TOA) (P<0.050), the first semester of chief residency (P<0.050), and conversion to laparotomy (P<0.001). Mean length of hospital stay was 40+/-24 hours. Factors such as advanced patient age (P<0.001), prolonged length of surgery (P<0.001), PID+/-TOA (P<0.001), first semester of chief residency (P<0.050), conversion to laparotomy (P<0.001), and blood transfusion (P<0.050) significantly increased the length of hospital stay. The conversion rate to laparotomy was 4.6% (n=17), and it was significantly associated with advanced women age (OR 1.11; 95% CI, 1.05-1.17, P<0.001) and PID+/-TOA (OR 6.04; 95%CI, 2.17-16.62, P<0.001). Postoperative complications were recorded in 3 (0.81%) patients. CONCLUSION: Laparoscopic management of gynecologic emergencies by senior residents and a chief resident within an organized resident training program is feasible. These results reinforce the relevance of a well-structured residency endoscopic training program. PMID- 20579998 TI - Variant anatomy of the uterine artery in a Kenyan population. AB - OBJECTIVE: To investigate the uterine artery's origin, branching patterns, and relation to the ureter in a Kenyan population. METHOD: The uterine arteries of the bodies of 53 girls and women were dissected at the University of Nairobi Department of Human Anatomy to study these patterns. Data were analyzed for frequency and the patterns are presented via digital macrographs. RESULTS: The uterine artery consistently originated as a branch of the internal iliac artery. It formed the second or third branch of the anterior trunk in 70.8% of cases; it ascended as a single branch, or from a bifurcation, or from a trifurcation in 76.4%, 17.1%, and 6.7% of cases; and lay posterior to the ureter in 3.8% of cases. In all, 46.2% of the uterine arteries studied varied from the classic description. CONCLUSION: About half of the uterine arteries had a nonclassic origin, branching pattern, or relation to the ureter-as a posterior relation to the ureter had not been previously described. Surgeons operating in the pelvis should be aware of this variant anatomy to avoid injury to the ureter and other organs. PMID- 20579999 TI - Delivery route preferences of urban women of low socioeconomic status. AB - OBJECTIVE: To identify the main determinants of mode of delivery preference among urban dwelling women of lower socioeconomic status (SES). METHODS: Over a 12 month period, a self-completion 36-item questionnaire was administered to a convenience sample of 308 women within the first 3 postpartum days. Non parametric tests were used for analysis. RESULTS: Study participants were mostly African American (>85%), single mothers (>75%), and unemployed (>=55%). Among the women, 85.7% had vaginal delivery (VD) and 14.3% had cesarean delivery (CD). Women who preferred CD (10%) were more likely to be concerned about a vaginal tear/episiotomy during VD, forceps, and a "big" baby compared with women who preferred VD, for whom "pushing the baby out myself" and "fear of cesarean" were the most important factors. In the final model of 7 factors, the 3 main factors found to positively impact maternal preference for CD were a vaginal cut during VD (P<0.001), higher mean BMI (P=0.001), and cesarean as the most recent delivery type (P<0.001). The total explained variance by this model was 46%. CONCLUSIONS: Short-term complications of a VD, higher BMI, and a previous cesarean delivery are the most significant factors that impact the preferences of women of lower SES for future mode of delivery. PMID- 20580000 TI - Performance of cryotherapy devices using nitrous oxide and carbon dioxide. AB - OBJECTIVE: To compare temperatures reached by 4 different cryotherapy devices commonly used to treat precancerous cervical lesions in low-resource countries using nitrous oxide (N(2)O) and carbon dioxide (CO(2)) as well as with and without a gas conditioner. METHODS: Bench testing was conducted using 4 different cryotherapy devices and locally obtained N(2)O and medical- and industrial-grade CO(2) refrigerant with and without a gas conditioner. A thermocouple was used to continuously measure the temperature of the cryotherapy tip. Comparison across the cryotherapy devices was based on the mean and lowest temperatures. RESULTS: Without the gas conditioner, all of the devices tested reached mean temperatures colder than -50 degrees C with N(2)O, although 2 devices reached warmer temperatures in a proportion of N(2)O tests. Only 2 of the devices reached mean temperatures colder than -50 degrees C with CO(2). One-way analysis of variance identified the device as the dominant factor for the temperature differences, while the gas was not a determinant of temperature variation. The gas conditioner hindered the performance of 2 of the devices, and only improved the performance of 1 device. CONCLUSION: Both N(2)O and CO(2) reach appropriate freezing temperatures with some cryotherapy devices. Performance of some cryotherapy devices is suboptimal. PMID- 20580001 TI - Ability of nurses to identify depression in primary care, secondary care and nursing homes--a meta-analysis of routine clinical accuracy. AB - PURPOSE: To clarify the ability of nurses and nursing assistants working in primary care, secondary care and nursing homes to identify depressed individuals using their clinical skills using meta-analysis of published studies. METHODS: Literature search, appraisal and meta-analysis. We located 22 studies reporting on the detection of depression, 4 involving primary care or community nurses; 7 involving hospital nurses and 11 from nursing homes.17 of 22 studies had specificity data. RESULTS: Across all 22 studies involving 7061 individuals, and a prevalence of 28.1% (95% CI=22.6-33.9%), practice and community nurses correctly identified 26.3% (95% CI=16.2-37.8%) of people with depression. They also correctly identified 94.8% (95% CI=91.3-97.4%) of the non-depressed. Nurses working in hospital settings correctly identified 43.1% (95% CI=31.9-54.8%) of people with depression and 79.6% (95% CI=71.5-86.7%) of the non-depressed. Those working in nursing homes correctly identified 45.8% (95% CI=38.1-53.6%) of people with depression and 80.0% (95% CI=68.6-88.7%) of the non-depressed. CONCLUSIONS: Nurses have considerable difficulty accurately identifying depression but are probably at least as accurate as medical staff. PMID- 20580002 TI - Sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students susceptible to psychosis. AB - BACKGROUND: Early interventions can improve treatment outcomes for individuals with major psychiatric disorders and with nonspecific symptoms but increasingly impaired cognitive perception, emotions, and behaviour. One way used to identify people susceptible to psychosis is through the schizotypal personality trait. Persons with schizotypal characteristics have been identified with the widely used Schizotypal Personality Questionnaire-Brief. However, no suitable instruments are available to screen individuals in the Taiwanese population for evidence of early psychotic symptoms. OBJECTIVES: The purpose of this study was to test the sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students' susceptibility to psychosis. DESIGN: Two-stage, cross-sectional survey design. SETTING AND PARTICIPANTS: The self-administered scale was tested in a convenience sample of 618 undergraduate students at a medical university in Taiwan. Among these students, 54 completed the scale 2 weeks apart for test-retest reliability, and 80 were tested to identify their susceptibility to psychosis. DATA COLLECTION AND ANALYSIS: In Stage I, participants with scores in the top 6.5% were classified as the high-score group (n=40). The control group (n=40) was randomly selected from the remaining participants with scores <15 and matched by gender. These 80 students were asked to participate in psychiatric interviews in Stage II. The instrument was tested for reliability using intraclass correlation coefficients and the Kuder-Richardson formula 20. The instrument was analysed for optimal sensitivity and specificity using odds-ratio analysis and receiver operating characteristic curves. RESULTS: The 22-item Chinese version of the Schizotypal Personality Questionnaire-Brief had a 2-week test-retest reliability of 0.82 and internal consistency of 0.76. The optimal cut-off score was 17, with odds ratios of 24.4 and an area under the receiver operating characteristic curves of 0.83. The instrument had a sensitivity of 80.0% and specificity of 85.9% in identifying undergraduate students' susceptibility to psychosis. CONCLUSIONS: The Chinese version Schizotypal Personality Questionnaire-Brief is a reliable instrument, but should not be used as a screening tool until its psychometric properties have been evaluated in more detail. Other screening tools need to be used in future studies with the CSPQ-B to improve the accuracy of identifying susceptibility to psychosis among young adults. PMID- 20580003 TI - Superparamagnetic lysozyme surface-imprinted polymer prepared by atom transfer radical polymerization and its application for protein separation. AB - Molecular imprinting as a promising and facile separation technique has received much attention because of their high selectivity for target molecules. In this study, the superparamagnetic lysozyme surface-imprinted polymer was prepared by a novel fabricating protocol, the grafting of the imprinted polymer on magnetic particles in aqueous media was done by atom transfer radical polymerization (ATRP), and the properties of the imprinted polymer were characterized in detail. Its high selective adsorption and recognition to lysozyme demonstrated the separation ability of the magnetic imprinted material to template molecule, and it has been used for quick and direct separation of lysozyme from the mixture of standard proteins and real egg white samples under an external magnetic field. Furthermore, the elution of lysozyme from the imprinted material was achieved by PEG/sulphate aqueous two-phase system, which caused lysozyme not only desorption from the imprinted materials but also redistribution in the top and bottom phase of aqueous two-phase system. The aqueous two-phase system exhibited some of the extraction and enrichment effect to desorbed lysozyme. Our results showed that ATRP is a promising method for the protein molecularly imprinted polymer preparation. PMID- 20580004 TI - Determination of organophosphorous pesticides in water using in-syringe ultrasound-assisted emulsification and gas chromatography with electron-capture detection. AB - An in-syringe ultrasound-assisted emulsification microextraction (USAEME) was developed for the extraction of organophosphorus pesticides (OPPs) from water samples. The OPPs subsequently analyzed gas chromatography (GC) using a microelectron capture detector (muECD). Ultrasound radiation was applied to accelerate the emulsification of microL-level low-density organic solvent in aqueous solutions to enhance the microextraction efficiency of OPPs in the sample preparation for GC-muECD. Parameters affecting the efficiency of USAEME, such as the extraction solvent, solvent volume, pH, salt-addition, and extraction time were thoroughly investigated. Based on experimental results, OPPs were extracted from a 5mL aqueous sample by the addition of 20microL toluene as the extraction solvent, followed by ultrasonication for 30s, and then centrifugation for 3min at 3200rpm, offered the best extraction efficiency. Detections were linear in the concentration of 0.01-1microg/L with detection limits between 1ng/L and 2ng/L for OPPs. Enrichment factors ranged from 330 to 699. Three spiked aqueous samples were analyzed, and recovery ranged from 90.1% to 104.7% for farm-field water, and 90.1% to 101.8% for industrial wastewater. The proposed method provides a simple, rapid, sensitive, inexpensive, and eco-friendly process for determining OPPs in water samples. PMID- 20580005 TI - A novel capillary electrophoretic method for determining methylglyoxal and glyoxal in urine and water samples. AB - Two non-electroactive biomarkers methylglyoxal (MGo) and glyoxal (Go) in urine and environmental water samples were determined for the first time by capillary electrophoresis with amperometric detection (CE-AD) after derivatizing with an electroactive compound 2-thiobarbituric acid. Experimental conditions of derivatization and CE-AD detection were optimized. Highly linear response was obtained for these two biomarkers over three orders of magnitude with good correlation (r(2)>0.999). The limits of detection (LODs) and limits of quantitation (LOQs) of MGo and Go were 0.2microgL(-1) and 1.0microgL(-1), 0.5microgL(-1) and 2.0microgL(-1), respectively. The average recovery and relative standard deviation (RSD) were within the range of 90.9-101.3% and 0.7 2.2%, respectively. The proposed CE-AD method provides a reliable and sensitive quantitative evaluation of MGo and Go in real sample matrices by employing relatively simple and inexpensive instrument. PMID- 20580006 TI - Ultrasound-assisted dispersive liquid-liquid microextraction for the determination of six pyrethroids in river water. AB - A simple ultrasound-assisted dispersive liquid-liquid microextraction method combined with liquid chromatography was developed for the preconcentration and determination of six pyrethroids in river water samples. The procedure was based on a ternary solvent system to formatting tiny droplets of extractant in sample solution by dissolving appropriate amounts of water-immiscible extractant (tetrachloromethane) in watermiscible dispersive solvent (acetone). Various parameters that affected the extraction efficiency (such as type and volume of extraction and dispersive solvent, extraction time, ultrasonic time, and centrifuging time) were evaluated. Under the optimum condition, good linearity was obtained in a range of 0.00059-1.52 mg L(-1) for all analytes with the correlation coefficient (r(2))>0.999. Intra-assay and inter-assay precision evaluated as the relative standard deviation (RSD) were less than 3.4 and 8.9%. The recoveries of six pyrethroids at three spiked levels were in the range of 86.2-109.3% with RSD of less than 8.7%. The enrichment factors for the six pyrethroids were ranged from 767 to 1033 folds. PMID- 20580007 TI - Investigation of pi-pi and ion-dipole interactions on 1-allyl-3-butylimidazolium ionic liquid-modified silica stationary phase in reversed-phase liquid chromatography. AB - 1-Allyl-3-butylimidazolium bromide ionic liquid [AyBIm]Br was prepared and used for the modification of mercaptopropyl-functionalized silica through surface radical chain-transfer addition. The obtained ionic liquid-modified silica (SiImBr) was characterized by elemental analysis, infrared spectroscopy, NMR spectroscopy, and thermogravimetric analysis. The selective retention behaviours of polycyclic aromatic hydrocarbons (PAHs) including some positional isomers were investigated using SiImBr as a stationary phase in reversed-phase liquid chromatography. The results showed that SiImBr presented multiple interactions including hydrophobic, pi-pi, and ion-dipole interactions during the separation of PAHs and dipolar compounds. However, it is proposed that pi-pi and ion-dipole interactions play important roles in the separation of PAHs and dipolar compounds. These results indicate that the ionic liquid-modified silica stationary phase is promising for future applications. A commercially available monomeric octadecylated silica (ODS) column and a custom-made poly(styrene) grafted silica (Sil-St(n)) column were used as references. PMID- 20580008 TI - Quantification of immunoglobulin G and characterization of process related impurities using coupled protein A and size exclusion high performance liquid chromatography. AB - The present work describes two HPLC-UV methods for multi-protein quantification using (i) only a Protein A sensor cartridge (Protein A HPLC) and (ii) the same Protein A cartridge in combination with a size exclusion HPLC column (PSEC-HPLC). The possibility to simultaneously quantify immunoglobulin G (IgG) besides a non binding protein such as bovine serum albumin (BSA) increases the applicability of Protein A HPLC. Its most pronounced feature is its independence of the buffer system, pH-value and salt content of the investigated sample solvent, which includes cell media. A comparison with the state-of-the-art, the photometrical Bradford method, shows that Protein A HPLC is as sensitive as Bradford, but that it comes with an extended linear range of 4 orders of magnitude, ranging from 0.15 [microg abs] to 1 [mg abs] absolute injected protein amount. The applicability of the PSEC-HPLC method is demonstrated for the analysis of real cell culture feed samples. While Protein A binds IgG, the SEC-column distributes the feed impurities by their molecular weight. The peak area ratios of IgG and the feed impurities of interest are then plotted against the collected sample fraction. These Protein A-Size-Exclusion-Chromatographic diagrams (PSEC-plot) combine the performance information of feed impurities and IgG in a single plot. Further it is shown that both methods are suitable for the performance evaluation of antibody purification media using static as well as dynamic binding experiments performed on DEAE-Fractogel and Capto Adhere. The investigated test samples were "mock" protein solutions with increasing complexity ranging from simple PBS buffer to serum free cell media and "real" cell culture feed solutions. PMID- 20580009 TI - A study of the parameters affecting the accuracy of the total pore blocking method. AB - We report on a study wherein we investigate the different factors affecting the accuracy of the total pore blocking method to determine the interstitial volume of reversed-phase packed bed columns. Octane, nonane, decane and dodecane were all found to be suitable blocking agents, whereas heptane already dissolves too well in the applied fully aqueous buffers. The method of moments needs to be used to accurately determine the elution times, and a proper correction for the frit volume is needed. Failing to do so can lead to errors on the observed interstitial volume of the order of 2% or more. It has also been shown that the application of a high flow rate or a high pressure does not force the blocking agent out of the mesopores of the particles. The only potential source of loss of blocking agent is dissolution into the mobile phase (even though this is a buffered fully aqueous solution). This effect however only becomes significant after the elution of 400 geometrical column volumes, i.e., orders more than needed for a regular total pore blocking experiment. PMID- 20580010 TI - A new 1,3-dibutylimidazolium hexafluorophosphate ionic liquid-based dispersive liquid-liquid microextraction to determine organophosphorus pesticides in water and fruit samples by high-performance liquid chromatography. AB - The paper described a new ionic liquid, 1,3-dibutylimidazolium hexafluorophosphate, as extraction solvent for extraction and preconcentration of organophosphorus pesticides (fenitrothion, parathion, fenthion and phoxim) from water and fruit samples by dispersive liquid-liquid microextraction combined with high-performance liquid chromatography. The effects of experimental parameters, such as extraction solvent volume, disperser solvent and its volume, extraction and centrifugal time, sample pH, extraction temperature and salt addition, on the extraction efficiency were investigated. An extraction recovery of over 75% and enrichment factor of over 300-fold were obtained under the optimum conditions. The linearity relationship was also observed in the range of 5-1000 microgL(-1) with the correlation coefficients (r(2)) ranging from 0.9988 to 0.9999. Limits of detection were 0.01-0.05 microgL(-1) for four analytes. The relative standard deviations at spiking three different concentration levels of 20, 100 and 500 microgL(-1) varied from 1.3-2.7, 1.4-1.9 and 1.1-1.7% (n=7), respectively. Three real samples including tap water, Yellow River water and pear spiked at three concentration levels were analyzed and yielded recoveries ranging from 92.7 109.1, 95.0-108.2 and 91.2-108.1%, respectively. PMID- 20580011 TI - Ion-pair high-performance liquid chromatography with diode array detection coupled to dual electrospray atmospheric pressure chemical ionization time-of flight mass spectrometry for the determination of nucleotides in baby foods. AB - A liquid chromatography with diode array detection coupled to dual electrospray atmospheric pressure chemical ionization time-of-flight mass spectrometry (HPLC/ESI-APCI-TOF-MS) method is described for the rapid determination of five monophosphate nucleotides (cytidine 5'-monophosphate, uridine 5'-monophosphate, adenosine 5'-monophosphate, inosine 5'-monophosphate and guanosine 5' monophosphate) in baby foods. The method is based on the deproteinisation of foods and direct analysis of nucleotides by ion-pair HPLC using isocratic elution with a mobile phase of 5% (v/v) methanol and 95% (v/v) 0.1 M formate buffer (pH 5.5) containing 0.01 M N,N-dimethylhexylamine (DMHA) at a flow-rate of 0.7 mL min(-1). The HPLC was hyphenated with two different detection systems, photodiode array (DAD) and ESI-APCI-TOF-MS in negative mode. The method was validated for linearity, detection and quantitation limits, selectivity, accuracy and precision. The recoveries obtained for spiked samples were satisfactory for all the analytes. The method was successfully applied to the analysis of nucleotides in different baby and/or functional food samples, as cereals, purees and dairy products. A study was also carried out on the stability of nucleotides in acidified dairy infant food with pasteurized yoghourt and follow-on formulae samples stored at room temperature and at 30 degrees C. PMID- 20580012 TI - Use of hydrous manganese dioxide as a potential sorbent for selective removal of lead, cadmium, and zinc ions from water. AB - Selective removal of three toxic metal ions, Pb(II), Cd(II), and Zn(II), from aqueous solution by amorphous hydrous manganese dioxide (HMO) was evaluated. Two polymeric exchangers, a polystyrene-sulfonic cation exchanger, D-001, and an iminodiacetic acid chelating exchanger, Amberlite IRC 748, were involved for comparison. Hydrogen ion release is accompanied by metal uptake onto HMO, implying that metal sorption could be generally represented by an ion-exchange process. As compared to both exchangers, HMO exhibits preferable sorption toward the toxic metals in the presence of Ca(II) ions at greater levels. FT-IR of the HMO samples laden with different metals indicate that Ca(II) uptake onto HMO is mainly driven by outer-sphere complexation, while that of three toxic metals might be related to inner-sphere complex formation. In addition, uptake of heavy metals onto HMO approaches equilibrium quickly and the exhausted HMO particles can be regenerated readily for repeated use by HCl solution. The results reported strongly display the potential of HMO as an economic and selective sorbent for removal of toxic metals from contaminated waters. PMID- 20580013 TI - pH-controlled interfacial assembly and disassembly of highly luminescent blue emitting Zn(x)Cd(1-x)S/dodecylamine complexes. AB - We present a robust strategy for assembling and disassembling of highly luminescent blue emitting Zn(x)Cd(1-x)S/dodecylamine (DDA) complexes via a facile water/chloroform interface. Firstly, thioglycolic acid (TGA)-stabilized ternary Zn(x)Cd(1-x)S nanocrystals (NCs) were synthesized in aqueous solution. And then, relying upon the facile water/chloroform interfacial platform, such NCs are assembled into the flake-like microstructures under the direction of DDA molecules when the pH of the water phase is adjusted into an optimal acidic range. Simultaneously, the NCs are transferred from the water into the chloroform phase due to the electrostatic interactions between carboxyl groups and amino of DDA molecules. Interestingly, by reversibly adjusting the pH of the water phase into an optimal basic range, the flake-like Zn(x)Cd(1-x)S/DDA complexes are disassembled into separate NCs and DDA, and these NCs are reversibly transferred back into the water phase. The photoluminescence (PL) quantum yield (QY) of Zn(x)Cd(1-x)S/DDA complexes after interfacial assembly is improved to 55% from 6%. Particularly, a QY of about 22% still retains for the Zn(x)Cd(1-x)S NCs even after the interfacial disassembly. PMID- 20580014 TI - Helix--rod transition in a nanospring. AB - A model of helical spring is described whose effective pitch and length are decided by the balance of the attractive van der Waals and repulsive hydration and electrical double layer forces. Also the electric contribution to the curvature free energy is taken into account. The stability of the nanospring is investigated and it is shown that the spring becomes unstable and jumps to its extended state on increase of electrostatic repulsion beyond a limit implying a jump in viscosity of suspension of springs in the solution. The magnitude of the jump and threshold potential are investigated. PMID- 20580015 TI - Preparation of microspherical alpha-zirconium phosphate catalysts for conversion of fatty acid methyl esters to monoethanolamides. AB - The performance of solid catalysts and catalyst supports is generally believed to be dependent on their morphology, surface area, and architecture. In order to fully exploit their attractive properties in actual practical applications, layered zirconium phosphate materials should be fabricated into macroscopic form. Here, we report the fabrication of microscopic spheres of alpha-zirconium phosphate (alpha-ZrP) by a spray-drying process. The layered alpha-ZrP nanoparticles were originally obtained using a synthesis route involving separate nucleation and aging steps (SNAS). The resulting products are composed of nanosize alpha-ZrP particles aggregated into solid microspheres with a diameter of 5-45 microm and a sphericity of 0.80. After calcination at 573 K, surface area of 43.8 m(2)/g could be obtained for alpha-ZrP microspheres, which is larger than that of the alpha-ZrP powder after similar thermal treatment (36.2 m(2)/g). Furthermore, the number of acidic sites of the alpha-ZrP microspheres is greater than for the alpha-ZrP powder due to its unique textual properties and higher surface area. The acylation reaction of fatty acid methyl esters (methyl stearate) with ethanolamine to form monoethanolamides was chosen as a probe reaction to evaluate the catalytic activity of the resulting microspherical alpha ZrP materials, which showed high activity compared to the sample in the form of powders, with about 92.9% methyl stearate conversion at 393 K for 12 h. The enhanced performance in the reaction is determined by the large surface area and the increased number of acidic sites in the multiple-scales porosity of alpha-ZrP microspheres. PMID- 20580016 TI - Recyclable hollow Pd-Fe nanospheric catalyst for Sonogashira-, Heck-, and Ullmann type coupling reactions of aryl halide in aqueous media. AB - Hollow Pd-Fe nanospheres were fabricated through a vesicle-assisted chemical reduction method. With the characterization of X-ray diffraction, selected area electron diffraction, X-ray photoelectron spectroscopy, scanning electron micrography, transmission electron micrography, and N(2) physisorption experiment, the resulting Pd-Fe material was identified to be hollow spherical with mesoporous shell. During aqueous Sonogashira-, Heck-, and Ullmann-type coupling reactions of aryl halide, the as-prepared hollow Pd-Fe nanospheres exhibited much higher activity than the dense counterpart nanoparticles. The enhanced reactivity was attributed to both the hollow chamber structure and the promotional effect of Fe-dopants, which provided more Pd active sites for the reactants. Moreover, this hollow material displayed other advantages such as low cost, recyclability and easy experimental handling. PMID- 20580017 TI - Patent ductus arteriosus management: what are the next steps? PMID- 20580018 TI - Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008. AB - OBJECTIVES: To estimate the rates of hospitalization with seasonal influenza in children aged <18 years from a large, diverse surveillance area during 2003 to 2008. STUDY DESIGN: Through the Emerging Infections Program Network, population based surveillance for laboratory-confirmed influenza was conducted in 10 states, including 5.3 million children. Hospitalized children were identified retrospectively; clinicians made influenza testing decisions. Data collected from the hospital record included demographics, medical history, and clinical course. Incidence rates were calculated with census data. RESULTS: The highest hospitalization rates occurred in children aged <6 months (seasonal range, 9 30/10 000 children), and the lowest rates occurred in children aged 5 to 17 years (0.3-0.8/10 000). Overall, 4015 children were hospitalized, 58% of whom were identified with rapid diagnostic tests alone. Forty percent of the children who were hospitalized had underlying medical conditions; asthma (18%), prematurity (15% of children aged <2 years), and developmental delay (7%) were the most common. Severe outcomes included intensive care unit admission (12%), respiratory failure (5%), bacterial coinfection (2%), and death (0.5%). CONCLUSIONS: Influenza-associated hospitalization rates varied by season and age and likely underestimate true rates because many hospitalized children are not tested for influenza. The proportion of children with severe outcomes was substantial across seasons. Quantifying incidence of influenza hospitalization and severe outcomes is critical to defining disease burden. PMID- 20580019 TI - Quantification of the relative contribution of environmental and genetic factors to variation in cystic fibrosis lung function. AB - OBJECTIVE: To assess the relative contributions of environmental and genetic factors to variation in cystic fibrosis (CF) lung disease. STUDY DESIGN: Genetic and environmental contributions were quantified by use of intrapair correlations and differences in CF-specific forced expiratory volume in 1 second measures from 134 monozygous twins and 272 dizygous twins and siblings while in different living environments (ie, living with parents vs living alone), as well as by use of intraindividual differences in pulmonary function from a separate group of 80 siblings. RESULTS: Pulmonary function among monozygous twins was more similar than among dizygous twin and sibling pairs, regardless of living environment, affirming the role of genetic modifiers in CF pulmonary function. Regression modeling revealed that genetic factors account for 50% of pulmonary function variation, unique environmental or stochastic factors (36%), and shared environmental factors (14%; P < .0001). The intraindividual analysis produced similar estimates for the contributions of the unique and shared environment. The shared environment effects appeared primarily because of living with a sibling with CF (P = .003), rather than factors within the parental household (P = .310). CONCLUSIONS: Genetic and environmental factors contribute equally to pulmonary function variation in CF. Environmental effects are dominated by unique and stochastic effects rather than common exposures. PMID- 20580021 TI - Sodium bicarbonate administration and outcome in preterm infants. AB - The short-term outcomes of sodium bicarbonate therapy in preterm infants were investigated by retrospective analysis of 165 of 984 infants who received sodium bicarbonate. The infants treated with sodium bicarbonate were more immature and had greater severity of illness and more adverse outcomes. Sodium bicarbonate therapy did not improve the blood pH. PMID- 20580022 TI - Altered brain function directly related to structural abnormalities in people at ultra high risk of psychosis: longitudinal VBM-fMRI study. AB - BACKGROUND: Several studies have indicated that people with prodromal signs of psychosis show alterations in the structure and function of the brain when they first present to clinical services. However, the longitudinal course of these abnormalities, and how they relate to subsequent clinical and functional outcome is relatively unclear. METHODS: A cohort of subjects at ultra high risk of psychosis were studied using functional magnetic resonance imaging (fMRI) in conjunction with the N-Back task, and volumetric MRI at first clinical presentation and again after one year. Levels of psychopathology and global functioning were assessed at the same time points using the CAARMS, PANSS, and the GAF scale. RESULTS: At baseline, the high risk group showed reduced activation during the task in the left middle frontal gyrus, supramarginal gyrus and inferior parietal lobule, and reduced gray matter volume in the left middle and medial frontal gyri, left insula and the right anterior cingulate gyrus. Within the high-risk group, there was a positive correlation between the magnitude of the functional and structural alterations in the left middle frontal gyrus. Between presentation and follow up, the severity of perceptual disorder and thought disorder (rated by the CAARMS), and of general psychopathology (rated by the PANSS general score) decreased, and the level of global functioning improved. This clinical and functional improvement was associated with a longitudinal increase in activation in the anterior cingulate and right parahippocampal gyrus. The change in anterior cingulate response was directly correlated with the improvement in the GAF score. CONCLUSIONS: In subjects presenting with prodromal signs of psychosis, reduced prefrontal activation during a working memory task is associated with a reduction in gray matter volume in the same area. Changes in anterior cingulate activation were correlated with functional improvement in this group, consistent with the role of this region in multiple cognitive and social processes. PMID- 20580023 TI - Temporal trend, spatial distribution, and terrestrial sources of PBDEs and PCBs in Masan Bay, Korea. AB - Congener specific determination of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) was carried out in 21 surface sediment samples and a sediment core from Masan Bay, Korea. Among the 40 PBDE congeners targeted only 29 were detectable. PBDE congener profile within sediments was dominated by BDE-209 followed by BDEs-99, -47, -153 and -183, sequentially. In surface sediments, the average SigmaPBDEs levels approached that of average SigmaPCBs values. However, trends observed in the sediment core suggest that this pattern will alter over time and result in higher surface sediment PBDE concentrations than PCBs in future. Various diffuse and point sources for PBDEs and PCBs were identified in this location. Shipping and other industrial activities were associated with PCB contamination while domestic and industrial waste discharges corresponded with PBDE contamination. The average concentration for PBDEs and PCBs in surface sediments were 5.7, 7.2 ng/g dry weight, respectively. PMID- 20580024 TI - Prediction of algal blooms using genetic programming. AB - In this study, an attempt was made to mathematically model and predict algal blooms in Tolo Harbor (Hong Kong) using genetic programming (GP). Chlorophyll plays a vital role in blooms and was used in this model as a measure of algal bloom biomass, and eight other variables were used as input for its prediction. It has been observed that GP evolves multiple models with almost the same values of errors-of-measure. Previous studies on GP modeling have primarily focused on comparing GP results with actual values. In contrast, in this study, the main aim was to propose a systematic procedure for identifying the most appropriate GP model from a list of feasible models (with similar error-of-measure) using a physical understanding of the process aided by data interpretation. Evaluation of the GP-evolved equations shows that they correctly identify the ecologically significant variables. Analysis of the final GP-evolved mathematical model indicates that, of the eight variables assumed to affect algal blooms, the most significant effects are due to chlorophyll, total inorganic nitrogen and dissolved oxygen for a 1-week prediction. For longer lead predictions (biweekly), secchi-disc depth and temperature appear to be significant variables, in addition to chlorophyll. PMID- 20580025 TI - [Frozen section doesn't reduce the number of reoperations for cancer after hemithyroidectomy]. AB - FUNDAMENTALS AND OBJECTIVES: Frozen section (FS) constitutes a diagnostic procedure in patients following hemithyroidectomy. It is used to diagnose malignant lesions and to avoid reoperations. Our objective is to confirm this test as useless to rule out cancer. PATIENTS AND METHODS: Retrospective and comparative trial between two series of patients following hemithyroidectomy. G I: 179 patients operated in 1995-2002. In this period we performed systematic FS. Sensitivity (S), specificity (E) and predictive values (PPV, NPV) are analyzed. G II: 126 patients were operated between 2003-2008. Selective FS was performed (23 patients). Both groups are compared: hospital stay, number of FS, percentage of cancer, definitive biopsy and reoperations. RESULTS: Data analyzed in the first period: S: 48%, E: 100%, PPV: 100%, NPV: 90%, positive likelihood ratio>10, negative likelihood ratio 0.52. When both periods are compared no significant differences between reoperations are found. CONCLUSION: FS during hemithyroidectomy does not reduce reoperations for cancer. PMID- 20580026 TI - [Liver transplantation for pancreatic carcinoid tumor with metastasis]. PMID- 20580027 TI - [Factors associated with an abnormal ankle-braquial index in a cohort of patients with HIV-1 infection]. AB - INTRODUCTION AND OBJECTIVES: An abnormal ankle-braquial index (ABI) has been related to a higher vascular mortality in the general population. People with HIV infection have a higher prevalence of abnormal ABI than general population. Our aim was to study that prevalence in a cohort of patients with HIV chronic infection and associated factors with an abnormal ABI. METHODS: ABI was calculated consecutively in all the patients who agreed to participate. Abnormal ABI was defined as that lower than 0.9 or higher than 1.3. Demographic variables and those related to vascular risk, HIV infection status and antiretroviral therapy were assessed. RESULTS: 231 patients collaborated in the study, and 25% of them had abnormal ABI (<0.9 in only 3 patients). Age, hypertension, lipid lowering agents use, vascular risk using Framingham equation, proportion of AIDS, CD4 nadir, years with the infection and protease inhibitors use were greater in the group with abnormal ABI. In logistic regression, lipid lowering agents use (OR: 0.39, CI95%: 0.16-0.94) and protease inhibitors use (OR: 2.59, CI95%: 1.33 5.05) remained in the model. CONCLUSION: Protease inhibitors use is associated with abnormal ABI, overall with an ABI greater than 1.3. PMID- 20580028 TI - [Copper deficiency after bariatric surgery simulating a myelodysplastic syndrome]. PMID- 20580029 TI - Effect of hormone replacement therapy on plasma lipoprotein levels and coronary atherosclerosis progression in postmenopausal women according to type 2 diabetes mellitus status. AB - Type 2 diabetes mellitus is associated with dyslipidemia and with an increased risk of coronary heart disease (CHD). Our objective was to compare the effects of hormone replacement therapy (HRT) on plasma lipoproteins and coronary disease progression in postmenopausal women with and without diabetes. Study subjects were participants in the Estrogen Replacement and Atherosclerosis trial, a placebo-controlled, randomized trial of HRT (conjugated equine estrogen 0.625 mg/d with or without medroxyprogesterone acetate 2.5 mg/d) in postmenopausal women with established CHD (mean age, 65 +/- 7 years). Plasma remnant lipoprotein levels and high-density lipoprotein (HDL) subpopulation levels were measured at baseline and year 1. Quantitative coronary angiography was assessed at baseline and at follow-up. At baseline, remnant lipoprotein levels were significantly higher and HDL cholesterol (HDL-C) levels were significantly lower in diabetic women than in women without diabetes. Hormone replacement therapy lowered remnant lipoproteins and increased HDL-C and large HDL particle levels in both groups. However, during HRT, levels of these parameters were still significantly worse in diabetic women than in nondiabetic women. A significant interaction between HRT and diabetes status, with greater increases in plasma atheroprotective HDL alpha1 particles in nondiabetic women than in diabetic women during HRT, was observed. Coronary heart disease progressed significantly more in women with diabetes than in women without diabetes. Our findings indicate that diabetes attenuates the HRT related increase in atheroprotective HDL alpha1 particles. Faster progression of coronary atherosclerosis in women with diabetes could be mediated in part by a worse lipoprotein profile in these women than in women without diabetes, both before and during HRT. PMID- 20580030 TI - Pedometer use is beneficial for type 2 diabetes mellitus patients if included in educational programs. PMID- 20580031 TI - Association of serum lycopene and brachial-ankle pulse wave velocity with metabolic syndrome. AB - Metabolic syndrome (MetS) is known to inversely correlate with antioxidant status. Recently, it has been reported that MetS is associated with arterial stiffness, a composite risk factor for early atherosclerosis. In addition, our recent study for healthy women showed an inverse relationship between arterial stiffness and circulating lycopene. Therefore, this study aimed to investigate the interrelationship between arterial stiffness, antioxidant status, and the risk of MetS. Korean men (N = 299) were subgrouped according to the number of MetS risk factors (RF 0, RF 1-2, RF >= 3). Anthropometric parameters, brachial ankle pulse wave velocity (baPWV; a marker of arterial stiffness), antioxidants (lycopene, beta-carotene, alpha-tocopherol), lipid profiles, glucose, insulin, and oxidative stress (low-density lipoprotein [LDL] particle size, oxidized LDL) were measured. Corresponding to the number of MetS RF, baPWV (1306 +/- 17, 1364 +/- 16, and 1420 +/- 33 cm/s; P < .001) and insulin resistance (1.5 +/- 0.1, 1.9 +/- 0.1, and 2.7 +/- 0.2; P < .001) gradually increased after adjustment for age, body mass index, smoking, and drinking, whereas serum lycopene among antioxidants and LDL particle size gradually decreased (0.036 +/- 0.001, 0.031 +/- 0.001, and 0.028 +/- 0.001 mmol/L; P = .004 and 23.9 +/- 0.1, 23.7 +/- 0.1, and 23.3 +/- 0.1 nm; P < .001, respectively). Brachial-ankle pulse wave velocity inversely correlated with serum lycopene after adjustment for the above confounders, blood pressure, insulin resistance, and oxidative stress (r = -0.136, P < .05). Oxidative stress markers also significantly correlated with baPWV as well as serum lycopene. Study subjects were divided into 2 groups by the median level of serum lycopene. When serum lycopene was lower than median level (<= 0.0294 mmol/L), baPWV was significantly higher in MetS subjects than non-MetS subjects (1436 +/- 41 vs 1367 +/- 23 cm/s) after adjustment for age, body mass index, smoking, drinking, and oxidative stress (P = .041). However, when serum lycopene levels were high, no statistically significant difference was observed between the 2 subject groups (1386 +/- 36 vs 1326 +/- 13 cm/s). In conclusion, our result shows the interrelationship between circulating lycopene, baPWV, and MetS. In addition, much enhanced baPWV in MetS may be associated with lower lycopene concentration. PMID- 20580032 TI - Serum adiponectin is associated with homocysteine in elderly men and women, and with 5,10-methylenetetrahydrofolate reductase (MTHFR) in a sex-dependent manner. AB - Plasma homocysteine associates positively with cardiovascular disease. C-to-T substitution at base 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene associates with increased plasma homocysteine. The association of adiponectin with cardiovascular disease is unclear. This study of survivors of a 30-year cohort of the Jewish Israeli population, 310 men and 273 women (mean age, 70.5 +/- 7.0 years for both), investigated the relationship between adiponectin and homocysteine, and between adiponectin and the MTHFR C677T genotype. Serum adiponectin associated positively with total homocysteine in both men (r = 0.27, P < .001) and women (r = 0.22, P < .001). In women, the TT MTHFR genotype associated with lower median adiponectin levels, 8.98 mg/L, compared with 9.88 and 10.57 mg/L for TC and CC, respectively (P = .05; CC vs TT, P = .01). In men, the trend was opposite, but not statistically significant: 7.90, 7.03, and 6.88 mg/L for TT, TC, and CC genotypes, respectively (P = .5). This study demonstrated a positive association between homocysteine and adiponectin in both elderly men and women and a statistically significant association between adiponectin and MTHFR C677T genotypes in women only. PMID- 20580033 TI - Replication of recently described type 2 diabetes gene variants in a South Indian population. AB - Recent genomewide association studies have identified several new gene variants associated with type 2 diabetes mellitus (T2D) mostly in European populations. These need to be replicated in other populations. We studied 926 unrelated T2D and 812 normal glucose-tolerant subjects randomly selected from the Chennai Urban Rural Epidemiology Study in Southern India. A total of 45 single nucleotide polymorphisms (SNPs) from 15 genes and 13 unannotated loci identified from recent genomewide association T2D studies were genotyped. Only 6 of 45 SNPs studied were replicated in this South Indian population. Three SNPs-rs7756992 (P = .007), rs7754840 (P = .015), and rs6931514 (P = .029)-of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population. Large scale studies are needed in our population to validate our findings. PMID- 20580034 TI - Epigallocatechin gallate-mediated protection against tumor necrosis factor-alpha induced monocyte chemoattractant protein-1 expression is heme oxygenase-1 dependent. AB - Flavonoids have been suggested to protect against atherosclerosis via their antioxidant and anti-inflammatory properties. Heme oxygenase-1 (HO-1) is an enzyme that plays an important role in the vascular system, and its induction may provide a protective role against atherosclerosis. We hypothesize that flavonoids can down-regulate endothelial inflammatory parameters by modulating HO-1 regulated cell signaling. We focused on the role of HO-1 and its major metabolic product, bilirubin, on mechanisms of tumor necrosis factor-alpha-induced endothelial cell activation and protection by the catechin epigallocatechin gallate (EGCG). Pretreatment with EGCG inhibited the secretion of monocyte chemoattractant protein-1 and the activation of activator protein-1 in porcine aortic endothelial cells stimulated with tumor necrosis factor-alpha. Moreover, EGCG up-regulated the expression of HO-1 and further induced the secretion of bilirubin. The observed anti-inflammatory effects of EGCG were mimicked by the HO 1 inducer cobalt protoporphyrin and abolished by HO-1 gene silencing. These data suggest that the protective properties of flavonoids, such as EGCG, against endothelial inflammation may be regulated in part though induction of HO-1 and subsequent activator protein-1 signaling. PMID- 20580035 TI - Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population. AB - Statin treatment and exercise training can reduce markers of inflammation when administered separately. The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein (CRP), monocyte toll-like receptor 4 (TLR4) expression, and CD14+CD16+ monocyte population size. Thirty three hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) groups. A third group of physically active hypercholesterolemic subjects served as a control (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in an exercise training program (3d/wk). Measurements were made at baseline (Pre), week 10 (Mid), and week 20 (Post), and included TLR4 expression on CD14+ monocytes and CD14+CD16+ monocyte population size as determined by 3-color flow cytometry. Serum CRP was quantified by enzyme-linked immunosorbent assay. TLR4 expression on CD14+ monocytes was higher in the R group at week 20. When treatment groups (R and RE) were combined, serum CRP was lower across time. Furthermore, serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point. When all groups (R, RE, and AC) were combined, TLR4 expression was greater on inflammatory monocytes (CD14+CD16+) compared with classic monocytes (CD14+CD16-) at all time points. In conclusion, rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes. The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population, suggesting an additive anti-inflammatory effect of exercise. PMID- 20580036 TI - Systemic hemodynamics in relation to glucose tolerance: the Health 2000 Survey. AB - The influence of impaired glucose metabolism--that is, impaired fasting glucose, impaired glucose tolerance (IGT), and type 2 diabetes mellitus diabetes (DM2)--on systemic hemodynamics is largely unknown. Therefore, we investigated the associations of glucose metabolism disturbances with stroke index (SI), cardiac index, systemic vascular resistance index (SVRI), arterial pulse wave velocity (PWV), and heart rate among Finnish adults (N = 389; mean age, 58.3 +/- 7.9 years) participating in the Health 2000 Survey. Systemic hemodynamic parameters were measured using the whole-body impedance cardiography device, and an oral glucose tolerance test (OGTT) was performed to evaluate glucose tolerance status. We found a decreasing trend for SI and increasing trends for SVRI and PWV according to the worsening of glucose tolerance (P for trend < .003 for all). In pairwise comparisons, SI was lower in the impaired fasting glucose group (P = .041) and the IGT group (P < .001) as compared with the normal glucose tolerance (NGT) group. Systemic vascular resistance index was higher in the IGT group (P = .045) and the DM2 group (P = .043) than in the NGT group. Subjects with IGT or DM2 had higher arterial PWV (10.7 +/- 0.2 m/s, P < .001 and 11.7 +/- 0.5 m/s, P = .001, respectively) than subjects with NGT (9.5 +/- 0.1 m/s). Moreover, 2-hour glucose in OGTT was an independent determinant of SVRI and PWV (P < .001 and P = .005, respectively) in multivariable linear regression models. In conclusion, the present study demonstrates that glucose intolerance, even without DM2, associates with several adverse changes in systemic hemodynamics and that 2-hour glucose in OGTT is an independent determinant of SVRI and PWV. These findings support the systematic evaluation of glucose tolerance status in the estimation of cardiovascular risk among the middle-aged population. PMID- 20580037 TI - Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease. AB - The novel adipokines vaspin, obestatin, and apelin-36 are associated with insulin resistance and the components of the metabolic syndrome. We assayed circulating levels of these molecules and examined their association with clinical, biochemical, and histologic phenotypes in patients with nonalcoholic fatty liver disease (NAFLD). Serum levels of vaspin, obestatin, and apelin-36 were assayed by enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 81 controls. We analyzed associations between adipokines and the characteristics of patients with NAFLD using multivariable linear regression models. Univariable analysis showed that concentrations of vaspin and apelin-36 were significantly higher in patients with NAFLD than in controls, whereas no differences in obestatin levels were found. Serum vaspin levels showed a statistically significant association with C-reactive protein (r = 0.378, P < .001) and liver fibrosis scores (r = 0.401, P < .001), whereas apelin-36 levels showed a modest association with homeostasis model assessment of insulin resistance (r = 0.204, P < .01). After stepwise linear regression analysis, serum vaspin levels were the only independent predictor of liver fibrosis scores in patients with NAFLD (beta = 0.37, t = 3.99, P < .01). Serum vaspin levels are raised in patients with NAFLD regardless of potential confounders and represent an independent predictor of liver fibrosis scores. These findings support further investigation of this novel adipokine in metabolic liver diseases. PMID- 20580038 TI - Stronger associations of sagittal abdominal diameter with atherogenic lipoprotein subfractions than waist circumference in middle-aged US white and Japanese men. AB - Both sagittal abdominal diameter (SAD) and waist circumference (WC) highly correlate with visceral adipose tissue (VAT) being linked to an atherogenic lipoprotein profile. However, it is uncertain whether SAD is a better correlate of atherogenic lipoprotein subfractions than WC. We examined relative associations of SAD vs WC with lipoprotein subfractions for US white and Japanese men, concurrently examining the associations of VAT vs subcutaneous adipose tissue with lipoprotein subfractions. A population-based sample of 260 white and 282 Japanese men aged 40 to 49 years was examined for VAT and subcutaneous adipose tissue by computed tomography; SAD and WC by a portable sliding-beam caliper and a measuring tape, respectively; and lipoprotein subfractions by nuclear magnetic resonance spectroscopy. Both SAD and WC were significantly and positively associated with large very low-density lipoprotein and total and small low-density lipoprotein particle concentrations, and inversely associated with large high-density lipoprotein particle concentration for both white and Japanese men. In body mass index-adjusted regression models, the significant associations of SAD remained for both white and Japanese men, whereas those of WC became nonsignificant for white men. When SAD and WC were simultaneously included into the body mass index-adjusted models, the associations of SAD remained significant and statistically stronger than those of WC for both white and Japanese men. Furthermore, the pattern of the associations of SAD with those lipoprotein subfractions was comparable to that of the associations of VAT. Sagittal abdominal diameter was comparable to VAT and stronger than WC in the associations with atherogenic lipoprotein subfractions for middle-aged, nondiabetic, white and Japanese men. PMID- 20580039 TI - Association of interleukin-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus. AB - Many factors have been implicated in the onset of type 2 diabetes mellitus (T2DM). Recently, immune response and inflammation were suggested to play certain roles in the development and complications of T2DM. The aim of this study is to investigate the putative correlation between the promoter polymorphisms of interleukin-4 (IL-4), one of the immune-regulatory type 2 helper T-cell cytokines, and T2DM. Genomic DNA from 425 Taiwanese T2DM patients and 148 nondiabetic control study subjects were extracted, and their IL-4 promoter polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Both of the distribution of IL-4 C-589T (P = .013) and C-34T (P = .05) genotypes were significantly different between T2DM patients and control subjects. Significant association between IL-4 C-589T alleles (P = .002) and T2DM, as well as C-34T alleles and T2DM (P =.024), was also identified. In addition, a statistically significant association between homologous IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol levels was observed. Our results suggested that IL-4 promoter polymorphisms are associated with T2DM. A significant association between IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol level was observed as well. The above results suggested that IL-4 may participate in lipid metabolism and diabetic susceptibility. PMID- 20580040 TI - Body fat changes and activity of tumor necrosis factor alpha system--a 5-year follow-up study. AB - Obesity is associated with subclinical, chronic, and systemic immune activation characterized by increased serum concentration of proinflammatory cytokines released by adipose tissue. The aim of the present study was to determine the relationship between stage of development of obesity and changes in activity of tumor necrosis factor (TNF) system during 5-year follow-up observation. One hundred fifty-four women--102 obese, 24 overweight, and 28 lean--without concomitant diseases were examined for the first time from 2000 to 2001. After 5 years, 57 obese, 12 overweight, and 14 lean subjects were reexamined. In addition to anthropometric measurements, body composition was determined by the bioimpedance method; and serum concentrations of glucose, lipids, insulin, TNF alpha, and soluble TNF receptors (sTNFRs) were measured. Only reexamined subjects were included in the analysis. After 5 years, fat mass increased significantly in 46 (66.7%) overweight or obese women and in all lean subjects (39.0 +/- 12.3 vs 47.3 +/- 13.6 kg, P < .001; 14.8 +/- 3.7 vs 20.6 +/- 5.4 kg, P < .01, respectively), whereas it decreased in 23 (33.3%) overweight or obese subjects (41.3 +/- 12.5 vs 37.2 +/- 14.0 kg, P < .005). The TNF-alpha levels increased significantly only in lean women (3.1 +/- 3.0 vs 5.6 +/- 2.0 pg/mL, P < .005), but remained unchanged in overweight and obese subjects regardless of fat mass changes. Serum concentrations of sTNFR1 and sTNFR2 decreased by 71% and 25% in obese, by 104% and 21% in overweight, and by 31% and 32% in lean group, respectively. The increase of plasma TNF-alpha level is an early event in abdominal fat accumulation. It seems that further fat mass gain does not enhance circulating TNF-alpha levels. PMID- 20580041 TI - Apolipoprotein C-I genotype and serum levels of triglycerides, C-reactive protein and coronary heart disease. AB - Apolipoprotein C-I (apoCI) is implicated in lipid metabolism and inflammatory response, both important risk factors for human heart disease. However, most findings come from in vitro or animal studies, whereas data on human apoCI are sparse. To elucidate the role of apoCI in human disease, we analyzed a functional polymorphism in the promoter region of the apoCI gene in relation to blood lipids, C-reactive protein (CRP), coronary artery disease (CAD), and myocardial infarction (MI). Rs11568822 is a 4-base pair insertion/deletion (Ins/Del) polymorphism, and the Ins allele leads to a higher transcription in vitro compared with the Del allele. This polymorphism was analyzed in the Intergene study, a case-control study for CAD (N = 1236), and the Stockholm Heart Epidemiology Program, a case-control study for MI (N = 2774). Subjects homozygous for the Ins genotype had significantly higher serum levels of triglycerides (P = .01 and P = .006) and lower serum levels of CRP (P = .02 and P < .0001) compared with all other subjects in both studies. Similar results were obtained when analyzing only the controls of both studies (P = .002 and P = .0002, triglycerides; P = .002 and P < .0001, CRP). However, apoCI was not associated with CAD or MI. In conclusion, our data show that apoCI genotype is associated with serum levels of triglycerides and CRP, confirming the role of apoCI in lipid metabolism and suggesting that it also influences inflammation. PMID- 20580042 TI - Enhanced long-chain fatty acid uptake contributes to overaccumulation of triglyceride in hyperinsulinemic insulin-resistant 3T3-L1 adipocytes. AB - The precise pathogenesis of obesity remains controversial. In obesity, diminished adipose glucose utilization suggests that some other substrates may be responsible for the adipose triglyceride (TG) overaccumulation. Here we attempted to evaluate if long-chain fatty acid (LCFA) flux was modulated by a physiologically relevant condition of hyperinsulinemia in 3T3-L1 adipocytes and if the altered LCFA influx might eventually contribute to the TG overaccumulation in obesity. The effects of prolonged insulin exposure to adipocytes on basal, insulin-stimulated LCFA uptake as well as intracellular LCFA metabolism were measured. Prolonged insulin exposure was found to induce insulin resistance (IR) yet enhance basal and insulin-stimulated LCFA uptake in normoglycemic condition, and the addition of high glucose exacerbated these abnormalities of both glucose and LCFA influx. Along with the enhanced LCFA uptake was an increase in the rates of intracellular LCFA deposition and incorporation into TG; but a decrease was found in basal and insulin-suppressive LCFA oxidation, as well as in isoproterenol-induced fatty acid efflux. Inhibition of either phosphatidylinositol 3-kinase or mitogen-activated protein kinase (MAPK) pathway did not prevent the induction of IR, whereas the enhanced basal and insulin stimulated LCFA uptake was abrogated by inhibition of MAPK pathway. In hyperinsulinemic insulin-resistant 3T3-L1 adipocytes, basal and insulin stimulated LCFA uptake tends to increase via a MAPK-dependent mechanism. The increment of LCFA influx predominantly accounts for TG overaccumulation, but not for mitochondrial oxidation, and is prone to retain within adipocytes. These findings may interpret the plausible mechanism of pathogenesis for obesity in hyperinsulinemia-associated IR. PMID- 20580043 TI - Proteomic analysis of cucumber seedling roots subjected to salt stress. AB - To understand metabolic modifications in plants under salt stress, the physiological and biochemical responses of cucumber (Cucumis sativus L. cv. Jinchun No. 2) seedlings to salt stress was investigated. The dry weight and fresh weight of cucumber seedling roots were significantly reduced by treatment with NaCl; Na(+) and Cl(-) were increased, while K(+) and K(+)/Na(+) ratio were decreased. To identify components of salt stress signaling, we compared the high resolution two-dimensional gel electrophoresis (2-DE) protein profiles of control and NaCl-treated roots, and the intensity of 34 protein spots varied. Of these spots, the identities of 29 (21 up-regulated and 8 down-regulated protein spots induced after salt stress) were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography electro-spray ionization tandem mass spectrometry (LC-ESI-MS/MS). The majority of the proteins had functions related to metabolism, energy and transport, and are involved in regulating reactions and defending against stress. A semi-quantitative reverse transcriptional-polymerase chain reaction (PCR) approach based on peptide sequences was used to compare transcript and protein accumulation patterns for 10 candidate proteins. Of these proteins, 8 patterns of induced transcript accumulation were consistent with those of induced protein accumulation. It is therefore likely that the response of the plant's proteome to NaCl stress is complex, and that the identified proteins may play an important role in regulating adaptation activities following exposure to NaCl stress in order to facilitate ion homeostasis. PMID- 20580044 TI - Age-stratified outcomes in elderly patients undergoing open and endovascular procedures for aortoiliac occlusive disease. AB - BACKGROUND: The elderly comprise a sizeable segment of patients with aortoiliac occlusive disease (AIOD). We analyzed outcomes in elderly patients who underwent open and endovascular procedures for AIOD. METHODS: Elderly patients with AIOD who underwent open and endovascular procedures in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database from 2004 to 2007 were identified. Patients were stratified into age groups: 65-69 years, 70 79 years, and 80 years or older. The clinical outcomes were complications and mortality; the economic outcomes were duration of stay and hospital cost. Both open and endovascular procedures were compared using chi(2) analysis, analysis of variance (ANOVA), and multivariate linear and logistic regression. RESULTS: Patients aged 80 years or older were more likely be nonelective admissions (43%), have a high Charlson Comorbidity Index (12%), and have iliac artery disease (63%, all P < .05). Patients aged 80 years or older who underwent open procedures had higher complication and mortality rates compared with younger patients (both P < .05). Endovascular procedures had a lower complication rate, duration of stay, and hospital cost for all age groups (P < .05). Mortality was significantly lower for endovascular treatment in patients aged 70 years or older (P < .05). A multivariate analysis showed patients aged 70 years or older were at increased risk of complications (P < .05). CONCLUSION: For both procedures, clinical outcomes worsen as patient age increases. In patients aged 70 years or older, endovascular treatment conferred a lower complication rate than open repair. PMID- 20580045 TI - Is breast conservation therapy a viable option for patients with triple-receptor negative breast cancer? AB - BACKGROUND: Triple-receptor negative breast cancers (TNBC) are aggressive neoplasms that lack estrogen-receptor, progesterone-receptor, and HER-2 expressions. Comparative analysis of breast conservation therapy (BCT) versus mastectomy for TNBC is reported sparsely. We hypothesized that, despite its aggressive behavior, TNBC can be managed with BCT. METHODS: Outcomes for 202 patients with TNBC who were treated with BCT or mastectomy were analyzed. Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank, independent samples t test, Cox proportional hazard model, and Chi-square. RESULTS: BCT was performed in 30% of patients. Isolated local recurrence rate for BCT and mastectomy was 0% and 10.6%, respectively (P = .02). Isolated regional recurrence rate for BCT and mastectomy was 1.6% and 1.4%, respectively (P = .61). Neither concomitant locoregional and distant recurrence rate (P = .73) nor isolated distant recurrence rate (P = .71) was significantly different between the BCT and mastectomy groups. The 5-year overall survival (OS) was better for the BCT group than the mastectomy group (89% vs 69%; P = .018); however, this was likely due to the mastectomy group having a larger neoplasm size (T3/T4: 4% BCT vs 27% mastectomy; P = .0002), advanced N-disease (N2/3: 8% BCT vs 25% mastectomy; P = .0003), and advanced stage of disease (stage 3: 8% BCT vs 35% mastectomy; P < .0001). On multivariate analysis, surgical approach had no effect on either disease-free survival (P = .60) or OS (P = .19); only t-stage was an independent predictor of disease-free survival (P = .02), while N-stage was an independent predictor for OS (P = .03). CONCLUSION: Despite TNBC's aggressive behavior, breast conservation therapy is a viable option for selected patients with TNBC. PMID- 20580046 TI - Two-year skill retention and certification exam performance after fundamentals of laparoscopic skills training and proficiency maintenance. AB - BACKGROUND: The purpose of this study was to determine 2-year performance retention and certification exam pass rate after completion of a proficiency based fundamental laparoscopic skills (FLS) curriculum and subsequent interval training. METHODS: Surgery residents (postgraduate year [PGY]1-5, n = 91) were enrolled in an Institutional Review Board approved protocol. All participants initially underwent proficiency-based training on all 5 FLS tasks. Subsequently, available residents were enrolled every 6 months in an ongoing training curriculum that included retention tests on tasks 4 and 5, with mandatory retraining to proficiency if the proficiency levels were not achieved. The final retention test included the actual FLS certification examination for PGY4-5 trainees. RESULTS: A 96% participation rate was achieved for all curricular components during the 2-year study period (PGY3-5, n = 33). Skill retention at retention 1-4 was 83%, 94%, 98%, and 91% for task 4 and 85%, 95%, 96%, and 100% for task 5, respectively. All PGY4-5 (n = 20) residents passed the FLS certification examination, achieving 413 +/- 28 total score on the skills portion (passing score > or =270) and demonstrating 92% retention for all 5 tasks. CONCLUSION: Proficiency-based training with subsequent ongoing practice results in a very high level of skill retention after 2 years and uniformly allows trainees to pass the FLS certification examination. PMID- 20580047 TI - Dopamine and cAMP regulated phosphoprotein MW 32 kDa is overexpressed in early stages of gastric tumorigenesis. AB - BACKGROUND: Gastric adenocarcinoma is a leading cause of cancer mortality. The role of dopamine and cAMP regulated phosphoprotein MW 32 kDa (DARPP-32) overexpression in the gastric tumorigenesis cascade remains unclear. METHODS: The expression of DARPP-32 in the multistep carcinogenesis cascade was examined using immunohistochemistry analysis on 533 samples. The contribution of DARPP-32 in cellular transformation and molecular signaling was investigated using NIH3T3, AGS, and SNU16 cells. RESULTS: The composite expression score (CES), calculated from immunostaining patterns, increased significantly from normal or gastritis to metaplasia, dysplasia, and adenocarcinoma (P < .001). In patients with normal stomach or gastritis and tumor samples, a 76% and 77% chance, respectively, was found (P < .001) that CES was higher in the tumor. High median CES correlated with well- or moderately differentiated (P = .03) gastric adenocarcinomas. NIH3T3 cells transfected with DARPP-32 demonstrated increased levels of phospho-AKT and a 5-fold increase in the number of foci as compared with the control (P = .02). DARPP-32 expression in AGS cells led to increased protein levels of phospho-AKT and BCL-2. For validation, the knockdown of endogenous DARPP-32 expression in SNU16 cells using shRNA resulted in decreased levels of phospho-AKT phosphorylation and BCL-2. CONCLUSION: Our results suggest that DARPP-32 overexpression may participate in the transition to intestinal metaplasia and in the progression to neoplasia. The ability of DARPP-32 to transform NIH3T3 cells and to regulate AKT and BCL-2 underscores its possible oncogenic potential. PMID- 20580048 TI - Physician attitudes regarding advance directives for high-risk surgical patients: a qualitative analysis. AB - BACKGROUND: Advance directive (AD) use is uncommon in surgical patients, yet the exact reasons for this are unknown. Our aim was to identify and describe beliefs held by surgeons regarding ADs. A qualitative exploration of physicians' opinions of ADs for surgical patients was designed. This methodology is preferred to quantitative techniques, which are subject to bias when an issue's underlying themes are unknown. METHODS: A purposive sample of physicians, primarily surgeons performing high-risk operations, was interviewed using a semi-structured questionnaire. Representation from several subspecialties established maximum transferability. Data collection continued until theoretical saturation was achieved. Transcribed audiotapes were first coded independently and then collaboratively using a coding scheme developed through grounded theory and deductive approaches. Modeling identified themes and trends to ensure faithful data representation. RESULTS: Three significant themes emerged, illustrating the conflicting attitudes surgeons harbor with respect to ADs. Surgeons described a general benefit of ADs in providing a framework for discussion ("It [AD] is a useful framework to begin discussion in the end of life issues for the patient."), but they also exhibited frustration with the disconnect between reality and written ADs ("What they [patients] really mean and what the words say are totally different.") and felt conflicted between the battle for surgical cure and the treatment limitations that occur with ADs in practice ("[ADs] may tie a surgeon's hands that might influence my judgment in performing the operation."). CONCLUSION: Surgeons describe conflicting feelings about ADs for high-risk surgical patients. These beliefs and attitudes may be an underlying factor for the limited use of ADs by surgical patients. Methods for improving effective use of ADs in surgical practice must address these attitudes. PMID- 20580049 TI - Comparison of pharmacokinetics, intracellular localizations and sonodynamic efficacy of endogenous and exogenous protoporphyrin IX in sarcoma 180 cells. AB - PURPOSE: The aim of the present study was to investigate the differences in pharmacokinetics, sub-cellular localizations and sonodynamic efficacy between endogenous and exogenous protoporphyrin IX (endo-PpIX and exo-PpIX) in sarcoma 180 (S180) cells. MATERIALS AND METHODS: The 5-aminolevulinic acid (ALA)-derived endo-PpIX and exo-PpIX pharmacokinetic profiles were determined by the fluorescence intensity of cell extracts with a spectrophotometer based on a standard curve. The changes in their sub-cellular localization patterns over a prolonged incubation time were evaluated by laser scanning confocal microscopy. The cytotoxic effects of 5-ALA-mediated sonodynamic therapy (ALA-SDT) and exogenous PpIX-mediated sonodynamic therapy (PpIX-SDT) were also evaluated by the MTT assay. RESULTS: The exo-PpIX showed dose-dependent pharmacokinetics in which a plateau of intra- and extracellular content was observed 45min after administration. However, the amount of ALA-derived endogenous intracellular PpIX, as well as extracellular PpIX in the same samples, showed linear accumulation with incubation time, which was independent of ALA concentration. Fluorescent imaging revealed that the exo-PpIX mainly accumulated at the plasma membrane in the early stage, whereas the ALA-derived PpIX initially localized in the mitochondria. Cells displayed sonodynamic damage by the synthesized endo-PpIX after addition of 1mM ALA for 12h, but the cytotoxicity induced by the equivalent amount of exo-PpIX was much more significant with increasing ultrasound intensities. CONCLUSIONS: Our findings suggest that endo- and exo-PpIX in S180 cells differ not only in pharmacokinetics but also in sub-cellular localizations, which may affect their sonodynamic efficacy and mechanisms of inducing cell death. PMID- 20580050 TI - Fabrication and comparison of PMN-PT single crystal, PZT and PZT-based 1-3 composite ultrasonic transducers for NDE applications. AB - This paper describes fabrication and comparison of PMN-PT single crystal, PZT, and PZT-based 1-3 composite ultrasonic transducers for NDE applications. As a front matching layer between test material (Austenite stainless steel, SUS316) and piezoelectric materials, alumina ceramics was selected. The appropriate acoustic impedance of the backing materials for each transducer was determined based on the results of KLM model simulation. Prototype ultrasonic transducers with the center frequencies of approximately 2.25 and 5MHz for contact measurement were fabricated and compared to each other. The PMN-PT single crystal ultrasonic transducer shows considerably improved performance in sensitivity over the PZT and PZT-based 1-3 composite ultrasonic transducers. PMID- 20580051 TI - Autophagy protein ATG5 interacts transiently with the hepatitis C virus RNA polymerase (NS5B) early during infection. AB - Autophagy is an important cellular process by which ATG5 initiates the formation of double membrane vesicles (DMVs). Upon infection, DMVs have been shown to harbor the replicase complex of positive-strand RNA viruses such as MHV, poliovirus, and equine arteritis virus. Recently, it has been shown that autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Here, we identified ATG5 as an interacting protein for the HCV NS5B. ATG5/NS5B interaction was confirmed by co-IP and metabolic labeling studies. Furthermore, ATG5 protein colocalizes with NS4B, a constituent of the membranous web. Importantly, immunofluorescence staining demonstrated a strong colocalization of ATG5 and NS5B within perinuclear regions of infected cells at 2 days postinfection. However, colocalization was completely lacking at 5DPI, suggesting that HCV utilizes ATG5 as a proviral factor during the onset of viral infection. Finally, inhibition of autophagy through ATG5 silencing blocks HCV replication. PMID- 20580053 TI - Fecal coliform accumulation within a river subject to seasonally-disinfected wastewater discharges. AB - As pathogen contamination is a leading cause of surface water impairment, there has been increasing interest in the implications of seasonal disinfection practices of wastewater effluents for meeting water quality goals. For receiving waters designated for recreational use, disinfection during the winter months is often considered unnecessary due to reduced recreational usage, and assumptions that lower temperatures may reduce pathogen accumulation. For a river subject to seasonal disinfection, we sought to evaluate whether fecal coliforms accumulate during the winter to concentrations that would impair river water quality. Samples were collected from municipal wastewater outfalls along the river, as well as upstream and downstream of each outfall during the winter, when disinfection is not practiced, and during the summer, when disinfection is practiced. During both seasons, fecal coliform concentrations reached 2000-5000 CFU/100 mL, nearly an order of magnitude higher than levels targeted for the river to achieve primary contact recreational uses. During the summer, wastewater effluents were not significant contributors to fecal coliform loadings to the river. During the winter, fecal coliform accumulated along the river predominantly due to loadings from successive wastewater outfalls. In addition to the exceedance of fecal coliform criteria within the river, the accumulation of wastewater-derived fecal coliform along the river during the winter season suggests that wastewater outfalls may contribute elevated loads of pathogens to the commercial shellfish operations occurring at the mouth of the river. Reductions in fecal coliform concentrations between wastewater outfalls were attributed to dilution or overall removal. Combining discharge measurements from gauging stations, tributaries and wastewater outfalls to estimate seepage, dilution between wastewater outfalls was estimated, along with the percentage of the river deriving from wastewater outfalls. After accounting for dilution, the residual reductions in fecal coliform concentrations observed between outfalls were attributed to actual fecal coliform removal. The estimated rate of removal of 1.52 d(-1) was significantly higher than die-off rates determined by previous researchers at similarly low temperatures in laboratory batch experiments, indicating the potential importance of other removal mechanisms, such as predation or sedimentation. PMID- 20580054 TI - Enhancement of waste activated sludge aerobic digestion by electrochemical pre treatment. AB - Electrochemical technology with a pair of RuO(2)/Ti mesh plate electrode is first applied to pre-treat Waste Activated Sludge (WAS) prior to aerobic digestion in this study. The effects of various operating conditions were investigated including electrolysis time, electric power, current density, initial pH of sludge and sludge concentration. The study showed that the sludge reduction increased with the electrolysis time, electric power or current density, while decreased with the sludge concentration. Additionally, higher or lower pH than 7.0 was propitious to remove organic matters. The electrochemical pre-treatment removed volatile solids (VS) and volatile suspended solids (VSS) by 2.75% and 7.87%, respectively, with a WAS concentration of 12.9 g/L, electrolysis time of 30 min, electric power of 5 W and initial sludge pH of 10. In the subsequent aerobic digestion, the sludge reductions for VS and VSS after solids retention time (SRT) of 17.5 days were 34.25% and 39.59%, respectively. However, a SRT of 23.5 days was necessary to achieve equivalent reductions without electrochemical pre-treatment. Sludge analysis by Scanning Electron Microscope (SEM) images and infrared (IR) spectra indicated that electrochemical pre-treatment can rupture sludge cells, remove and solubilize intracellular substances, especially protein and polysaccharide, and consequently enhance the aerobic digestion. PMID- 20580052 TI - Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent resistant membranes and cell-cell fusion but not interaction with M protein. AB - Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses. PMID- 20580055 TI - Modelling the population dynamics and metabolic diversity of organisms relevant in anaerobic/anoxic/aerobic enhanced biological phosphorus removal processes. AB - In this study, enhanced biological phosphorus removal (EBPR) metabolic models are expanded in order to incorporate the competition between polyphosphate accumulating organisms (PAOs) and glycogen accumulating organisms (GAOs) under sequential anaerobic/anoxic/aerobic conditions, which are representative of most full-scale EBPR plants. Since PAOs and GAOs display different denitrification tendencies, which is dependent on the phylogenetic identity of the organism, the model was separated into six distinct biomass groups, constituting Accumulibacter Types I and II, as well as denitrifying and non-denitrifying Competibacter and Defluviicoccus GAOs. Denitrification was modelled as a multi-step process, with nitrate (NO(3)), nitrite (NO(2)), nitrous oxide (N(2)O) and di-nitrogen gas (N(2)) being the primary components. The model was calibrated and validated using literature data from enriched cultures of PAOs and GAOs, obtaining a good description of the observed biochemical transformations. A strong correlation was observed between Accumulibacter Types I and II, and nitrate-reducing and non nitrate-reducing PAOs, respectively, where the abundance of each PAO subgroup was well predicted by the model during an acclimatization period from anaerobic aerobic to anaerobic-anoxic conditions. Interestingly, a strong interdependency was observed between the anaerobic, anoxic and aerobic kinetic parameters of PAOs and GAOs. This could be exploited when metabolic models are calibrated, since all of these parameters should be changed by an identical factor from their default value. Factors that influence these kinetic parameters include the fraction of active biomass, relative aerobic/anoxic fraction and the ratio of acetyl-CoA to propionyl-CoA. Employing a metabolic approach was found to be advantageous in describing the performance and population dynamics in such complex microbial ecosystems. PMID- 20580056 TI - Detecting endocrine disrupting compounds in water using sulfur-oxidizing bacteria. AB - For the rapid and reliable detection of endocrine disrupting compounds in water, a novel toxicity detection methodology based on sulfur-oxidizing bacteria (SOB) has been developed. The methodology exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid in the presence of oxygen. The reaction results in an increase in electrical conductivity (EC) and a decrease in pH. When endocrine disrupting compounds were added to the system, the effluent EC decreased and the pH increased due to the inhibition of the SOB. We found that the system can detect these chemicals in the 50-200 ppb range, which is lower than many whole-cell biosensors to date. The SOB biosensor can detect toxicity on the order of min to h which can serve as an early warning so as to not pollute the environment and affect public health. PMID- 20580057 TI - Cultivation practices affect heavy metal migration between soil and Vicia faba (broad bean). AB - Pot-test experiments were conducted to study the influences of mulching and fertilizing on the migration of heavy metals from soil to Vicia faba (broad bean). Semi-transparent film was used to mulch soil. Swine manure compost was mixed with soil at a rate of 50 mg kg(-1) to fertilize the soil. Broad bean was grown for several months until fruits were formed. Soils and bean parts were sampled to analyze and fractionate heavy metals (Cd, Cu, Fe, Mn, Pb, and Zn). Mulching promoted an obvious growth of broad bean. Fertilizing decreased soil pH and increased organic matter content and conductivity. Mulching reduced the exchangeable metal fractions by 5-52%. Fertilizing, in contrast, increased the exchangeable fractions of most of the metals except Fe and Pb by 20-295%. While the two cultivations increased obviously metal concentrations in bean laminas as compared to un-mulched and un-fertilized controls, the levels of most of the metals except Pb decreased in bean fruits. No clear relationships existed in roots and caudices in terms of metal levels. Calculated bioconcentration factors (BCF) and transfer factors (TF) indicate that the cultivations had little influences on the metal enrichments in roots, but promoted their migration from roots to laminas. In particular, mulching greatly promoted the absorption and translocation of Fe, while fertilizing enhanced the bean fruit uptake of Pb. Further studies on the influence of cultivation practices on heavy metal migration in soil-plant systems are recommended to acquire more information for evaluation of crop safety. PMID- 20580058 TI - Environmental assessment of urban wastewater reuse: treatment alternatives and applications. AB - The main function of a Wastewater Treatment Plant is to minimize the environmental impact of discharging untreated water into natural water systems. Also a Wastewater Treatment Plant may get a resource from wastewater carrying out a tertiary treatment on the treated wastewater which can be reused in non-potable applications. Water reuse strategies are intended to address the problem of water scarcity without aggravating other environmental problems, thus reflecting the need of their environmental assessment. In this paper we used Life Cycle Assessment to evaluate different disinfection treatments (chlorination plus ultraviolet treatment, ozonation and ozonation plus hydrogen peroxide) and to assess the environmental advantages and drawbacks of urban wastewater reuse in non-potable applications. To do so, we compared the environmental impacts of producing 1m(3) of water for non-potable uses from reclaimed water, potable water and desalinated water sources. The calculation has used current operating data from a Wastewater Treatment Plant located in the Mediterranean area, although the results can be applied to any other plant with similar technology. The ozonation and ozonation plus hydrogen peroxide disinfection treatment technologies have similar environmental profiles. However most of the indicators are about 50% higher than the ultraviolet disinfection except for the acidification (100% higher) and photochemical oxidation (less than 5%). Non-potable uses (both agricultural and urban uses) of reclaimed water have environmental and economical advantages. Reuse of treated wastewater is particularly beneficial when it can replace desalinated water. Consequently, reclaimed water should be promoted for non-potable uses, when there is scarcity of freshwater. PMID- 20580059 TI - Disinfection by-product formation following chlorination of drinking water: artificial neural network models and changes in speciation with treatment. AB - Artificial neural network (ANN) models were developed to predict disinfection by product (DBP) formation during municipal drinking water treatment using the Information Collection Rule Treatment Studies database complied by the United States Environmental Protection Agency. The formation of trihalomethanes (THMs), haloacetic acids (HAAs), and total organic halide (TOX) upon chlorination of untreated water, and after conventional treatment, granular activated carbon treatment, and nanofiltration were quantified using ANNs. Highly accurate predictions of DBP concentrations were possible using physically meaningful water quality parameters as ANN inputs including dissolved organic carbon (DOC) concentration, ultraviolet absorbance at 254nm and one cm path length (UV(254)), bromide ion concentration (Br(-)), chlorine dose, chlorination pH, contact time, and reaction temperature. This highlights the ability of ANNs to closely capture the highly complex and non-linear relationships underlying DBP formation. Accurate simulations suggest the potential use of ANNs for process control and optimization, comparison of treatment alternatives for DBP control prior to piloting, and even to reduce the number of experiments to evaluate water quality variations when operating conditions are changed. Changes in THM and HAA speciation and bromine substitution patterns following treatment are also discussed. PMID- 20580060 TI - Trends in NO(x) abatement: a review. AB - Implementation of stringent regulations of NO(x) emission requires the development of new technologies for NO(x) removal from exhaust gases. This article summarizes current state of NO(x) abatement strategy. Firstly, the influence of NO(x) on environment and human health is described. The main focus is put on NO(x) control methods applied in combustion of fossil fuels in power stations and mobile vehicles, as well as methods used in chemical industry. Furthermore the implementation of ozone and other oxidizing agents in NO(x) oxidation is emphasized. PMID- 20580061 TI - Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: a pilot study. AB - INTRODUCTION: We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke. MATERIALS AND METHODS: We included 66 patients with acute ischaemic stroke admitted between 1 and 7 hours after the onset of clinical symptoms. We collected plasma samples upon admission and on the two following days and measured AP-FXIII and subunit levels by ELISA. Clinical stroke severity was assessed by NIHSS stroke score. RESULTS: AP-FXIII could be detected in 34 patients upon admission (range 0.2-26.3 ng/ml), on day 1 in 15 patients (0.2-10.4 ng/ml), and on day 2 in 11 patients (0.1-15.1 ng/ml. AP-FXIII was higher in patients with severe stroke. Lower AP-FXIII levels upon admission were associated with clinical improvement. FXIII-A and FXIII-B subunit levels decreased significantly from day 0 to day 1. CONCLUSIONS: For the first time, we detected AP-FXIII in patients upon an acute thrombotic event. The decrease in FXIII subunit levels during acute ischaemic stroke is evidence for ongoing coagulation activity and FXIII consumption. Our results suggest that FXIII activation and concomitant AP-FXIII release might be associated with an unfavourable short-term clinical outcome. Larger studies are needed to further investigate whether AP FXIII might serve as a diagnostic and/or prognostic marker for acute thrombotic diseases. PMID- 20580062 TI - Selectins in human amniotic fluid and cord blood plasma. A preliminary report. PMID- 20580064 TI - The predictive value of measurement of SUVmax and SCC-antigen in patients with pretreatment of primary squamous cell carcinoma of cervix. AB - OBJECTIVE: Use of positron emission tomography/computed tomography (PET/CT) and serum squamous cell carcinoma (SCC) antigen (SCC-ag) as predictors for poor prognosis of pretreatment of primary SCC of cervix. METHODS: The distribution of cases that scored positive for each of the biological parameters examined was correlated with maximum SUV (SUVmax) of PET/CT and serum SCC-ag for 52 participants prior to radiotherapy (RT) with or without concurrent chemotherapy (CCRT) with pretreatment of primary SCC of cervix. RESULTS: There were significant correlations between the SUVmax of the primary tumor and tumor maximum size (P=0.027), and the lymph node metastasis (P=0.039). The serum SCC-ag had a statistically significant association with the clinicopathological parameters such as FIGO stage (P=0.045) and tumor maximum size (P=0.008), although there was no correlation noted between the SUVmax of the primary tumor and the serum SCC-ag (R=0.155). The high SUVmax of the primary tumor (>= 15.6) plus lymph node metastasis (a short-axis diameter of over 10mm with a SUVmax >= 3.5) were significant predictors for poor prognosis when compared with the low SUVmax of the primary tumor (<15.6) or the high SUVmax of the primary tumor plus negative lymph node metastasis (a short-axis diameter of under 10mm or SUVmax <3.5) (overall survival rate; P=0.0211). CONCLUSIONS: The present findings indicate that the high SUVmax of the primary tumor plus lymph node metastasis with pretreatment of primary SCC of cervix may be associated with a poor prognosis. PMID- 20580065 TI - Characterization, isolation and culture of primordial germ cells in domestic animals: recent progress and insights from the ovine species. AB - Primordial germ cell (PGC) allocation, characterization, lineage restriction, and differentiation have been extensively studied in the mouse. Murine PGC can be easily identified using markers as alkaline phosphatase content or the expression of pluripotent markers such as Pou5f1, Nanog, Sox2, Kit, SSEA1, and SSEA4. These tools allowed us to clarify certain aspects of the complex interactions of somatic and germinal cells in the establishment of the germ cell lineage, its segregation from the neighbouring somatic tissue, and the guidance mechanisms during migration that direct most of the germ cells into the genital ridges. Few data are available from other domestic animals and here we reported our preliminary studies on the isolation, characterization, and in vitro culture of sheep PGCs. Sheep PGCs can be identified with the markers previously used in mouse, but, in some cases, these markers are not coherently expressed in the same cell depending on the grade of differentiation and on technical problems related to commercial antibodies used. Pluripotency of PGCs in culture (EGCs) from domestic animals also needs further evaluation even though the derivation of embryonic pluripotent cell lines from large mammals may be an advantage as they are more physiologically similar to the human and perhaps more relevant for clinical translation studies. Comprehensive epigenetic reprogramming of the genome in early germ cells, and derived EGCs including extensive erasure of epigenetic modifications, may be relevant for gaining insight into events that lead to reprogramming and establishment of totipotency. EGCs can differentiate in vitro in a various range of tissues, form embryonic bodies, but in many cases failed to generate tumours when transplanted into immunodeficient mice and are not able to generate germline chimeric animals after their transfer. Such incomplete information clearly indicates the urge to improve the studies on derivation of stem cells in farm animals and shows the need for a multidisciplinary investigation in order to create farm animal models to set up suitable ethical and technical systems for cell regenerative therapies in humans. PMID- 20580063 TI - Management of rare ovarian cancers: the experience of the French website "Observatory for rare malignant tumours of the ovaries" by the GINECO group: interim analysis of the first 100 patients. AB - BACKGROUND: Non-epithelial ovarian cancers are rare; their natural history is poorly understood and prognostic factors remain unclear. A French website (www.ovaire-rare.org) was developed to collect clinical cases and tumour samples in order to better define prognostic factors and develop specific trials. We report the results of the first 100 patients with germ cell (GCT) and sex cord stromal (SCT) tumours. METHODS: All adult patients with histological evidence of GCT or SCT at diagnosis or first relapse were eligible. RESULTS: From 03/2002 to 06/2009, 180 patients were included; the first 100 were evaluated. Patient characteristics were: histology: SCT 61%, GCT 30%, others 5%; median age: 43 years; median tumour size: 12 cm; FIGO stages I-II: 83%, III-IV: 17%. Central pathology review (67 patients) differed from initial diagnosis in 37%. Fifty-six percent of the patients had initial conservative surgery and 10% lymph node dissection; 56 patients received chemotherapy. Eleven of the 78 first-line patients relapsed and 5 died; the 5-year OS rate was 94% and the median PFS 64 months. CONCLUSIONS: This online observatory allows assessing medical practice for GCT and SCT in France. Histological discrepancies between diagnosis and second opinion confirm the need for systematic review before treatment. Extension to other rare gynaecologic malignancies is on-going. PMID- 20580066 TI - Evaluation of fresh and frozen-thawed fowl semen by flow cytometry. AB - The aim of this study was to assess the spermatozoal viability, acrosome integrity, mitochondrial activity, and DNA status in the frozen-thawed fowl semen with the use of flow cytometry. The experiment was carried out on 10 sexually adult roosters of meat type line Flex. The semen was collected three times a week by dorso-abdominal massage method, then pooled and subjected to cryopreservation using "pellet" method and Dimethylacetamide (DMA) as a cryoprotectant. For cytometric analysis the fresh and frozen-thawed semen was extended with EK diluent to a final concentration of 50 million spermatozoa per mL. Sperm membrane integrity was assessed with dual fluorescent probes SYBR-14 and propidium iodide (PI). Acrosomal damages were evaluated using phycoerythrin-conjugated lectin PNA from Arachis hypogaea. The percentage of live spermatozoa with functional mitochondria was estimated using Rhodamine 123 (R123) and PI. The spermatozoal DNA integrity was measured by sperm chromatin structure assay (SCSA). The freezing-thawing process decreased the viability, mitochondrial activity in the chicken sperm and increased the percentage of dead cells with ruptured and intact acrosomes, and also the percentage of spermatozoa with fragmented DNA. In conclusion, the present study indicates that fluorescent staining and flow cytometry may be useful for assessment of the changes of fowl semen quality caused by cryopreservation process. This technique allows precise examination of spermatozoa functional characteristic in a very short time. PMID- 20580067 TI - Identification of bovine CD52-like molecule by monoclonal antibody IVA-543: distribution of CD52-like molecule in the bull genital tract. AB - The bovine maturation-associated sperm membrane antigen CD52-like molecule has been analysed using a mouse anti-sperm monoclonal antibody developed against bull spermatozoa. The antigen recognised by monoclonal antibody IVA-543 was detected on blood mononuclear cells (including lymphocytes and monocytes) and on a minor population of polymorphonuclear leukocytes. The bovine CD52-like molecule is secreted by the epididymal epithelium and then it is inserted into the sperm membrane during the epididymal transport in the distal part of epididymis. The CD52-like molecule was absent from spermatozoa derived from testes, and the highest proportion of IVA-543-reactive sperm was observed in the cauda epididymis (91.6%). This study has shown that the new molecule identified on bovine cells has properties analogous to those previously described for CD52 molecules in man, mouse, rat, monkey, and dog. PMID- 20580068 TI - Umbilical artery doppler sonography in Saanen goat fetuses during singleton and multiple pregnancies. AB - The objective of this study was to evaluate the blood flow from the umbilical artery (UA) in healthy pregnant goats. Doppler sonography examinations were performed every two weeks in Saanen goats with a singleton (n = 5) or multiple (n = 4) pregnancy from 40 to 145 days of gestation. Fetal heart rates (FHR), pulsatility index (PI), and resistance index (RI) were recorded from the mid-cord site of the free-floating umbilical cord. FHR decreased gradually as the pregnancy progressed and significantly decreased during the last two examinations of all fetuses (P < 0.05). The mean PI level was dramatically different (P < 0.05) until 85 days of gestation, after which it reached a plateau level until parturition. Similar to PI, RI decreased by 85 days of gestation (P < 0.05), and decreased again by 130s gestation. No reverse or absent end-diastolic flow were observed in fetuses during any examinations. When comparing singleton and multiple pregnancies, there were no significant differences in UA pulsatility or resistance in fetuses seen. The middle of the second trimester was observed to be a threshold stage for indices in the pattern of caprine pregnancy. In conclusion, this work provides additional values that might be useful when evaluating singleton and multiple pregnancies, and may be evaluated in further studies regarding fetal monitoring. PMID- 20580069 TI - Economic consequences of reproductive performance in dairy cattle. AB - The net economic value of reproductive efficiency in dairy cattle was estimated using a stochastic dynamic simulation model. The objective was to compare the economic consequences of reproductive performance scenarios ("average" and "poor") of a cow having a good reproductive performance and to explore which reproductive factors have an important impact on economic efficiency. A "good" reproductive performance scenario was defined with 1 ovulation rate (POVU(i)), 0.7 estrus detection rate (PEst), 0.7 conception rate (PCon), 0.03 incidence rate of postpartum disorders prolonging the ovarian cyclicity (CO), 0.2 incidence rate of postpartum disorders reducing conception (ME), 0.05 embryonic death rate (ED), and voluntary waiting period (VWP) of 9 wks pp (post partum). In the current situation of dairy cows in the Netherlands, an "average" reproductive scenario (0.95 POVU(i), 0.5 PEst, 0.5 Pcon, 0.07 CO, 0.27 ME, 0.07 ED and VWP of 12 wks pp) and a "poor" reproductive scenario (0.90 POVU(i), 0.3 PEst, 0.3 Pcon, 0.11 CO, 0.33 ME, 0.09 ED and VWP of 15 wks pp) were identified. A sensitivity analysis was performed by comparing changes of single effect of factors in a good and poor scenario with the average scenario. The mean net economic loss (NEL(i)) compared with the good scenario was euro 34 and euro 231 per cow per year for the average and poor reproductive performance scenario, respectively. Increasing the calving interval resulted in greater economic loss. The important factors on the cost of reproductive efficiency were the involuntary culling cost and the return of milk production. Variation in PCon, PEst, ME, ED, and VWP had large impacts on economic benefits. PMID- 20580070 TI - Differences in testosterone, androstenone, and skatole levels in plasma and fat between pubertal purebred Duroc and Landrace boars in response to human chorionic gonadotrophin stimulation. AB - The concentrations of the boar taint compounds androstenone and skatole in plasma and fat, together with those of testosterone in plasma, were investigated in pubertal purebred Duroc and Landrace boars following stimulation with human chorionic gonadotrophin (hCG). Higher initial levels of androstenone and testosterone were found in Duroc than Landrace boars. Duroc boars, which were approximately ten days older than the Landrace boars, also showed a more advanced stage of spermatogenesis than Landrace boars. While Landrace boars had the highest skatole levels. Following stimulation with hCG the relative increases in testosterone, androstenone, and skatole concentrations were highest in Landrace boars. The level of androstenone in fat three days after hCG stimulation exceeded 1 microg/g fat in all stimulated boars. The decreases in plasma levels of androstenone and testosterone on Days 2 and 3 after hCG stimulation were more pronounced in Landrace than Duroc boars. However, unlike the plasma androstenone and testosterone levels, the plasma concentrations of skatole did not decrease on Days 2 and 3 following stimulation, but remained elevated on Day 3. These results indicate that the lower levels of testicular steroids in Landrace boars compared with Duroc boars was not due to a lower production capacity, but more likely to a faster disappearance of steroids in Landrace boars. In the present study, age, live weight, and testicular development did not significantly contribute to the variation in fat androstenone. The present data and previous reports on candidate genes related to androstenone biosynthesis and metabolism suggests that future selection against factors associated with boar taint remains a possible solution for the problem of boar taint in the swine industry. PMID- 20580071 TI - Changes in the histomorphology of the canine cervix through the oestrous cycle. AB - The importance of canine reproduction is steadily increasing and little is known about the canine cervix so far. The aim of this study was to describe the histomorphology of the canine cervix and to determine its correlation to the stage of oestrous cycle and to circulating concentrations of progesterone (P4) and estradiol-17beta (E2), respectively. Ovariohysterectomy (OHE) was performed in 33 non-pregnant, healthy, intact bitches in defined stages of oestrous cycle (proestrus N = 5, estrus N = 7, early diestrus N = 5, late diestrus N = 11, anestrus N = 5). The entire cervix was collected for histological evaluation of the epithelial layer (number of layers, thickness), the stroma (number of layers, thickness, density, structure, and distribution of elastic fibres) and the average area and density of cervical glands as well as blood vessels. These parameters were evaluated in all the three parts of the cervix (cranial, middle, and caudal or vaginal part). The cervix showed the typical structure with a superficial epithelium, a lamina propria with cervical glands and vascular structures and a tunica muscularis below. Folds in the superficial epithelium were only observed in 54% females (N = 18). Epithelial thickness (P < 0.0001), number of glands (P < 0.05), mean area of glands (P < 0.0001), mean area of venous vessels (P < 0.0001), number of arterial vessels (P = 0.02), number of mast cells and number of eosinophilic granulocytes per mm(2) (P < 0.01) were significantly influenced by the stage of cycle. The following factors were significantly influenced by the localisation: number of epithelial layers (P < 0.0001), thickness of stroma (P < 0.0001) and mean number of glands (P < 0.01). Only mean area of venous vessels was significantly influenced by the stage of cycle and the localisation (P < 0.01). Besides, P4 was significantly correlated to number of glands per mm(2) (P < 0.0001), mean area of venous vessels (P < 000.1) and number of mast cells (P < 0.01). This study provided detailed information about the histomorphological structure of the cervix in non-pregnant bitches and showed that the cervix undergoes cyclic changes during the canine oestrous cycle, in particular in association with circulating progesterone concentration. PMID- 20580072 TI - Accuracy of pregnancy specific protein-B test for early pregnancy diagnosis in dairy cattle. AB - The objective was to evaluate the accuracy of an ELISA for pregnancy specific protein B (PSP-B) for early pregnancy diagnosis in dairy cattle. Blood from lactating (>100 d postpartum) dairy cows (n = 738), was collected on Days 28, 30, and 35 (Day 0 = estrus), analyzed with an ELISA for PSP-B, and the cows designated as pregnant, probable, unlikely, or non-pregnant. Immediately after blood collection, transrectal ultrasonography (TRUS) was done for pregnancy diagnosis, and the results used as a criterion standard test for comparison with PSP-B. At Day 28, 46.3% were diagnosed by TRUS as pregnant. The PSP-B sensitivity was 93.9% on Day 28 and similar on Days 30 and 35. The PSP-B specificity, positive predictive value, negative predictive value, and accuracy were all >94% on Day 28 and similar on Days 30 and 35. However, the accuracy was significantly less compared to TRUS (P < 0.01). The percentage of all samples from cows that were probably pregnant or unlikely to be pregnant was 5.6%. At Days 28, 30, and 35, percentages of uncertain samples were 8.5, 4.8, and 3.3%, respectively (P < 0.01), and Kappa values were 0.92, 0.92, and 0.95. False negative and false positive results were attributed to low concentrations of PSP-B in pregnant animals and to persistence of pregnant concentrations of PSP-B in females with pregnancy loss, respectively. In conclusion, PSP-B ELISA was a sensitive, specific, and accurate test for pregnancy diagnosis (relative to TRUS) at Days 28, 30, and 35 after breeding. PMID- 20580073 TI - Vitrification of ICSI- and IVF-derived bovine blastocysts by minimum volume cooling procedure: effect of developmental stage and age. AB - The objective was to investigate the effects of developmental stage (fully expanded or expanding blastocysts) and/or age (harvested on Days 7 or 8) on post vitrification in vitro survival of bovine blastocysts derived from intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Post warming survival (re-expansion of blastocoele within 24 h) of ICSI-derived fully expanded blastocysts (80%) was similar to that of their IVF-derived counterparts (88%). However, the ability of ICSI-derived expanding blastocysts to survive vitrification procedures (61%) was lower than that of IVF-derived blastocysts (85%; P < 0.05), although the ICSI- and IVF-derived fresh blastocysts were of similar quality. The age of the blastocysts before vitrification did not affect cryotolerance for either ICSI-derived (73 and 59% for Days 7 and 8 embryos, respectively) or IVF-derived blastocysts (86% for both Days 7 and 8 embryos). At 24 h of post-warming culture, ICSI-derived blastocysts surviving vitrification contained a higher proportion of dead cells than their IVF-derived counterparts (5-13% vs. 2-4%; P < 0.05), but these proportions were not different from those of fresh control embryos. There was an adverse effect of vitrification on the ability of blastocysts to hatch within 72 h of culture only in IVF-derived Day 8 blastocysts (41 and 70% in vitrified and fresh control groups, respectively). In conclusion, the proportion of blastocysts that survived vitrification procedures was similar for ICSI- and IVF-derived bovine blastocysts if the former were cultured to the fully-expanded stage prior to vitrification, with no significant difference between embryos harvested on Day 7 versus Day 8. PMID- 20580074 TI - The HSP90AA1 sperm content and the prediction of the boar ejaculate freezability. AB - In a previous study we reported that the immunolabelling of GLUT3, HSP90AA1, and Cu/ZnSOD proteins on boar sperm did not show differences between good and poor freezability ejaculates, in terms of a qualitative analysis based on location and reactivity of these proteins at 17 degrees C and at 240 min post-thaw. Since predicting the ejaculate freezability is considerably important in sperm cryopreservation procedures, the objective of the present study was to quantify the expression of these three proteins in good and poor freezability ejaculates. For this purpose, 10 ejaculates from 9 Pietrain boars were cryopreserved and their sperm quality assessed in the three main steps of the freezing process (17 degrees C, 5 degrees C, and 240 min post-thaw). After this assessment, the 10 ejaculates were clustered for freezability on the basis of their sperm progressive motility and membrane integrity at 240 min post-thaw. From the whole ejaculates, only four good and four poor freezability ejaculates displaying the most divergent values were selected for a western blot assay using sperm samples coming from the three mentioned freezing steps. Protein levels through densitometry were significantly different between good and poor freezability ejaculates for Cu/ZnSOD at 240 min post-thaw (P 3 mo old) in Jodhpur, India, and to determine litter size, and the prevalence of fetal resorption in this population. The prevalence of estrus and pregnancy was determined in 5400 free-ranging bitches (trapped and released) at the time of ovariohysterectomy. In a separate study, the uteri and ovaries of 246 free-ranging bitches were examined to determine litter size and fetal resorption. The bitches exhibited seasonal estrus and pregnancy (P < 0.00001), with a higher percentage of bitches in estrus or pregnant during the late monsoon season (September to November) compared to the other three seasons. The mean litter size based on embryo/fetal counts was 4.6 (95% CI = 4.0-5.3; n = 40) and based upon placental site counts was 4.4 (95% CI = 3.9-4.8; n = 105). Prevalence of fetal resorption was 32.6% (95% CI = 20.5-47.5; n = 43) with a mean of 2.8 resorptions per litter in those with at least one resorption (95% CI = 1.8-3.8; n = 14). This was the first study to estimate previous litter size of non-pregnant, free-ranging dogs based upon placental sites. Litter size data from this study will be used in a population demographic model to predict the long-term impact of animal birth control (ABC) on the free ranging dog population in Jodhpur. Increasing the efforts to surgically sterilize bitches prior to the time of year of peak pregnancy or whelping will help maximize the impact of an ABC program on the Jodhpur free-ranging dog population. PMID- 20580081 TI - Capacitation inducers act through diverse intracellular mechanisms in cryopreserved bovine sperm. AB - The effect of various capacitation inducers, i.e. heparin, superoxide anion, bicarbonate, adenosine, and caffeine, and their role in intracellular mechanisms involved in capacitation, were studied in cryopreserved bovine sperm. Capacitation was determined by epifluorescence chlortetracycline, protein tyrosine phosphorylation, and the ability of capacitated sperm to undergo an acrosome reaction and fertilize in vitro matured oocytes. Participation of membrane adenylate cyclase and protein kinases (protein kinase A, protein kinase C, and protein tyrosine kinase) was evaluated indirectly (with specific inhibitors). Involvement of reactive oxygen species (ROS) was determined with scavengers of superoxide anion, hydrogen peroxide, or nitric oxide. Percentages of capacitated (27-29%) and acrosome-reacted sperm (23-26%) did not differ (P > 0.05) among various capacitation inducers. Significantly higher rates of IVF were obtained with heparin (43%) or bicarbonate plus caffeine (45%), when compared with control samples (17%). Adding the membrane adenylate cyclase inhibitor diminished capacitation rates with heparin (8%) or adenosine (10%). There was differential protein kinase participation in response to inducers; protein kinase inhibitors diminished cleavage rates in heparin-capacitated sperm relative to controls. There were differences between and within the studied inducers in protein tyrosine phosphorylation patterns. We inferred that capacitation in cryopreserved bovine sperm was promoted through diverse pathways. Mechanisms triggered by heparin, or caffeine plus bicarbonate-induced capacitation, involved activation of intracellular pathways to optimize fertilizing capability of cryopreserved bovine sperm. PMID- 20580082 TI - Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. AB - Over this decade, cell printing strategy has emerged as one of the promising approaches to organize cells in two and three dimensional engineered tissues. High resolution and high speed organization of cells are some of the key requirements for the successful fabrication of cell-containing two or three dimensional constructs. So far, none of the available cell printing technologies has shown an ability to concomitantly print cells at a cell-level resolution and at a kHz range speed. We have studied the effect of the viscosity of the bioink, laser energy, and laser printing speed on the resolution of cell printing. Accordingly, we demonstrate that a laser assisted cell printer can deposit cells with a microscale resolution, at a speed of 5 kHz and with computer assisted geometric control. We have successfully implemented such a cell printing precision to print miniaturized tissue like layouts with de novo high cell density and micro scale organization. PMID- 20580084 TI - Localisation of ABCA1 in first trimester and term placental tissues. PMID- 20580083 TI - Fetal-placental hypoxia does not result from failure of spiral arterial modification in mice. AB - OBJECTIVES: To determine if fetal-placental hypoxia is a primary outcome of defective spiral artery remodeling. STUDY DESIGN: Pregnancies in Rag2(-/-)Il2rg( /-) double knock-out mice, which fail to undergo normal physiological spiral arterial remodeling, were compared to syngeneic BALB/c control pregnancies. Mice at gestation day (gd)6, 8, 10, 12 and 18 were infused with Hypoxyprobe-1 before euthanasia to enable detection of cellular hypoxia by immunohistochemistry. RESULTS: In implantation sites of both phenotypes, trophoblast cells were reactive to Hypoxyprobe-1. No major differences were observed between the phenotypes in decidua or placenta at any gd or in gd18 fetal brain, lung, heart, liver or intestine or in maternal heart, brain, liver or spleen. Maternal kidneys from BALB/c were significantly hypoxic to Rag2(-/-)Il2rg(-/-) kidneys. CONCLUSIONS: In mice, lack of pregnancy-associated spiral artery remodeling does not impair oxygen delivery to the conceptus, challenging the concept that deficient spiral arterial remodeling leads to fetal hypoxia in human gestational complications such as preeclampsia and fetal growth restriction. The isolated hypoxic response of normal kidney has revealed that renal lymphocytes may have unique, tissue-specific regulatory actions on vasoconstriction that are pregnancy independent. PMID- 20580085 TI - Maternal apelin physiology during rat pregnancy: the role of the placenta. AB - OBJECTIVE: Apelin is a multifunctional peptide which is catabolized by the angiotensin-converting enzyme-related carboxypeptidase-2 (ACE2). The peptide is well known for its hemodynamic effects and its role in energy and fluid homeostasis. Pregnancy is a state of dramatically altered maternal hemodynamics and metabolism, but the role of apelin is unknown. To gain further insight in apelin physiology, we investigated relative tissue expression, plasma clearance and metabolic pathways of apelin in pregnant rats. METHODS: We measured maternal plasma apelin levels throughout normal rat gestation and examined relative apelin gene expression in several tissues, including the placenta. We documented apelin clearance using radiolabeled apelin and assessed maternal plasma levels in rats that underwent surgical reduction of the fetoplacental mass, thereby further examining the role of the placenta in apelin clearance. Finally, we localized apelin and ACE2 in the placenta and mesometrial triangle using immunohistochemistry. RESULTS: Maternal apelin plasma concentrations dropped by 50% between mid- and late gestation. Apelin expression was comparable between non pregnant and late-pregnant rats in non-reproductive tissues. The placenta showed low apelin gene expression compared to brain tissue. Apelin clearance was enhanced in term gestation as evidenced by a steeper decline of the slow phase of the elimination curve of radiolabeled apelin. Compared to sham-operated dams, maternal plasma apelin was raised by 23% in late-pregnant rats in which half of the fetoplacental units were removed at day 16 of gestation. ACE2 mRNA expression was detectable in late- but not mid-pregnancy placental tissue; immunohistochemically, ACE2 was primarily localized in the smooth muscle layer of fetal arterioles in the labyrinth. CONCLUSION: Maternal circulating apelin drops considerably between mid- and late- pregnancy owing to faster clearance. The current data suggest a role for placental ACE2 in the accelerated apelin metabolism. PMID- 20580086 TI - Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. AB - ESAs are increasingly used to treat anemia of lower risk MDS, even before RBC transfusion requirement. From a previously published patient cohort treated with ESAs, we selected 112 patients with de novo low or int-1 IPSS MDS with Hb<10 g/dl, serum EPO<500 UI/l and who had never been transfused. Erythroid response rate at 12 weeks was 63.1% (IWG 2006). In multivariate analysis, an interval between diagnosis and ESA onset<6 months, Hb level>9 g/dl, and serum EPO<100 UI/l predicted better response to ESA while shorter interval between diagnosis and ESA onset (p=0.01), lower serum EPO (p=0.04) and WHO diagnosis of RCMD-RS (p=0.03) were associated with longer response. Median interval from diagnosis to transfusion dependency was 80 months and 35 months, respectively, in patients with onset of ESA < 6 months and >= 6 months from diagnosis (p=0.007). Those results support early onset of ESA in lower risk MDS, to better avoid the consequences of anemia. Early introduction of ESA may also delay the need for RBC transfusions, hypothetically by slowing the disease course, but prospective studies are required to further assess this point. PMID- 20580087 TI - Cardioprotective effects of selenium on chromium (VI)-induced toxicity in female rats. AB - Acute exposure to hexavalent chromium compounds can cause cardiotoxicity. Our study pertains to the protective effect of selenium against K(2)Cr(2)O(7)-induced cardiotoxicity. Female Wistar rats were divided into four groups of six each: group I served as controls which received standard diet; group II received in drinking water K(2)Cr(2)O(7) alone (700 ppm); group III received both K(2)Cr(2)O(7) and Se (0.5 Na(2)SeO(3) mg/kg of diet); group IV received Se (0.5 mg/kg of diet) for 3 weeks. The exposure of rats to chromium promoted oxidative stress with an increase in malondialdehyde levels and a decrease in antioxidant non-enzymatic levels such as glutathione, non-protein thiol and vitamin C, while, an increase in glutathione peroxidase, superoxide dismutase and catalase activities was observed. However, plasma transaminases, lactate dehydrogenase activities, cholesterol, triglycerides and low density lipoprotein-cholesterol levels increased, and high density lipoprotein-cholesterol decreased. Coadministration of Se restored the parameters cited above to near-normal values. The histopathological findings confirmed the biochemical results. PMID- 20580088 TI - The soil-dwelling earthworm Allolobophora chlorotica modifies its burrowing behaviour in response to carbendazim applications. AB - Carbendazim-amended soil was placed above or below unamended soil. Control tests comprised two layers of unamended soil. Allolobophora chlorotica earthworms were added to either the upper or the unamended soil. After 72 h vertical distributions of earthworms were compared between control and carbendazim-amended experiments. Earthworm distributions in the carbendazim-amended test containers differed significantly from the 'normal' distribution observed in the control tests. In the majority of the experiments, earthworms significantly altered their burrowing behaviour to avoid carbendazim. However, when earthworms were added to an upper layer of carbendazim-amended soil they remained in this layer. This non avoidance is attributed to (1) the earthworms' inability to sense the lower layer of unamended soil and (2) the toxic effect of carbendazim inhibiting burrowing. Earthworms modified their burrowing behaviour in response to carbendazim in the soil. This may explain anomalous results observed in pesticide field trials when carbendazim is used as a control substance. PMID- 20580089 TI - Federally sponsored multidisciplinary research centers: Learning, evaluation, and vicious circles. AB - Despite the increasing investment in multi-year federally funded science and technology centers in universities, there are few studies of how these centers engage in learning and change based on information submitted from various agents in the oversight and evaluation process. One challenge is how to manage and respond to this evaluative information, especially when it is conflicting. Although the center can learn and adapt in response to this information, it can also become subject to a vicious circle of continuous restructuring and production of documentation to address various and potentially inconsistent recommendations. In this paper we illustrate the effects of such a dynamic based on our experiences as external evaluators of the $25 million NSF-funded Learning in Informal and Formal Environments (LIFE) Center. The case study presents an analysis of annual reports and strategic planning documents along with other sources of evidence to illustrate the evolution of center organizational approaches in response to evaluations by external review panels, center evaluators, program managers, and other external stakeholders. We conclude with suggestions for how evaluators may help centers ease the cost of learning and reduce the likelihood of a vicious circle. PMID- 20580091 TI - The plasma bradykinin-forming pathways and its interrelationships with complement. AB - The plasma bradykinin-forming cascade and the complement pathways share many elements, including cross-activation, common control mechanisms, and shared binding proteins. The C1 inhibitor (C1 INH) is not only the inhibitor of activated C1r and C1s, but it is the key control protein of the plasma bradykinin forming cascade. It inhibits the autoactivation of Factor XII, the ability of Factor XIIa to activate prekallikrein and Factor XI, the activation of high molecular weight kininogen (HK) by kallikrein, and the feedback activation of Factor XII by kallikrein. Thus in the absence of C1 INH (hereditary angioedema or acquired C1 INH deficiency) there is unimpeded formation of bradykinin leading to angioedema. Activated Factor XII (Factor XIIa, 80,000 kDa) is further cleaved by kallikrein or plasmin to yield Factor XII fragment (Factor XIIf, 30,000 kDa) and Factor XIIf can activate the C1r subcomponent of C1, particularly when C1 INH (which inhibits Factor XIIf) is absent. Once bradykinin is formed, it causes vasodilatation and increased vascular permeability by interaction with constitutively expressed B-2 receptors. However degradation of bradykinin by carboxypeptidase N (in plasma) or carboxypeptidase M (on endothelial cells) yields des-arg-9 (Kerbiriou and Griffin, 1979) bradykinin which interacts with B 1 receptors. B-1 receptors are induced in inflammatory states by cytokines such as Interleukin 1 and its interaction with bradykinin may prolong or perpetuate the vascular response until bradykinin is completely inactivated by angiotensin converting enzyme or aminopeptidase P, or neutral endopeptidase. The entire bradykinin-forming cascade is assembled and can be activated along the surface of endothelial cells in zinc dependent reactions involving gC1qR, cytokeratin 1, and the urokinase plasminogen activated receptor (u-PAR). Although Factors XII and HK can be shown to bind to each one of these proteins, they exist in endothelial cells as two bimolecular complexes; gC1qR-cytokeratin 1, which preferentially binds HK, and cytokeratin 1-u-PAR which preferentially binds Factor XII. The gC1qR, which binds the globular heads of C1q is present in excess and can bind either Factor XII or HK however the binding sites for HK and C1q have been shown to reside at opposite ends of gC1qR. Activation of the bradykinin-forming pathway can be initiated at the cell surface by gC1qR-induced autoactivation of Factor XII or direct activation of the prekallikrein-HK complex by endothelial cell derived heat-shock protein 90 (HSP 90) or prolylcarboxypeptidase with recruitment or Factor XII by the kallikrein produced. PMID- 20580092 TI - Videotaped evaluation of eyedrop instillation in glaucoma patients with visual impairment or moderate to severe visual field loss. AB - PURPOSE: Objectively evaluate the ability of visually disabled glaucoma patients to successfully administer a single drop onto their eye. DESIGN: Prospective, observational study. PARTICIPANTS: Experienced glaucoma patients with Early Treatment of Diabetic Retinopathy Study visual acuity (VA) of <= 6/18 (<= 20/60) >= 1 eye, or moderate or severe visual field damage in >= 1 eye. METHODS: Subjects were "low vision" (20/60 <= VA <20/200) or "blind" (light perception 6 months. Subjects used a mean of 1.9 +/- 1.1 bottles of intraocular pressure lowering medications to treat their glaucoma. Seventy-six percent (155/204) of subjects had severe visual field damage, with a mean deviation of -14.5 +/- 8.0. Twenty-six percent (54/204) had acuity of <= 20/200 in >= 1 eye, and subjects had a mean logarithm of minimal angle of resolution acuity of 0.8 +/- 0.9. Seventy one percent of subjects were able to get a drop onto the eye; only 39% instilled 1 drop onto the eye without touching the ocular surface, instilling a mean 1.4 +/ 1.0 drops, using 1.2 +/- 0.6 attempts. Of the 142 subjects who denied touching the bottle to the ocular surface, 24% did touch the bottle to the eye. Multiple factors were tested for ability to predict successful application of an eyedrop; however, only age (< 70 vs >= 70 years) was found to be a significant predictor for less successful instillation. CONCLUSIONS: In this video analysis of visually impaired glaucoma patients, we evaluated the difficulty this population has instilling eyedrops, most important, the use of multiple drops per instillation, potential contamination of a chronically used bottle, and poor patient understanding of the situation. Ability to self-administer eyedrops and cost considerations of wasted drops must be thought out before institution of glaucoma therapy. Efforts to determine better methods of eyedrop administration need to be undertaken. PMID- 20580093 TI - Long-term changes in refractive error in patients with accommodative esotropia. AB - PURPOSE: To evaluate changes in the spherical equivalent (SE) refractive error and astigmatism in Korean patients with accommodative esotropia. DESIGN: Retrospective cases series. PARTICIPANTS: A total of 111 patients with accommodative esotropia who received at least 2 years of follow-up after receiving prescription spectacles. METHODS: Patients were divided into groups according to the age at which spectacles were prescribed (youngest, middle, and oldest age groups), initial degree of SE refractive error (lowest, moderate, and highest SE group), initial degree of astigmatism (least, moderate, and most astigmatic group), and presence of amblyopia (amblyopic or nonamblyopic). Changes in SE refractive error and astigmatism were compared between groups. Factors that significantly influenced changes in refractive error were analyzed using mixed linear models. MAIN OUTCOME MEASURES: Changes in SE refractive error and changes in astigmatism according to the duration of time after the initiation of wearing spectacles. RESULTS: Patients were followed up for a mean of 7.55 +/- 3.59 years. Although an initial increase in SE was noted in the youngest-age group, an overall decreasing tendency in SE refractive error during the follow-up period was noted in the youngest (P < 0.01, mixed linear model), the middle (P < 0.01), and the oldest (P < 0.01) age groups. Amblyopic eyes showed greater decreases in SE compared with nonamblyopic eyes (P=0.01). The most hyperopic group showed the greatest decrease in hyperopia over time (P=0.01). The initial degree of hyperopia (P < 0.01) and amblyopia (P < 0.01) showed significant associations with changes in SE refractive error. The initial degree of astigmatism (P < 0.01) showed a significant association with changes in astigmatism. CONCLUSIONS: Patients with accommodative esotropia showed a continuous decrease in SE refractive error over time. Changes in refractive error in patients with accommodative esotropia may be influenced by both spectacle wearing and amblyopia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20580094 TI - Does gender influence response to differing psychotherapies by those with unipolar depression? AB - BACKGROUND: There have been few studies that have specifically examined for any impact of gender on response to psychotherapy for those with depression. We therefore undertook a review and report findings. METHOD: A literature review was conducted by first seeking to identify studies via relevant search engines and then examining a number of secondary sources. RESULTS: There was no clear or consistent evidence to suggest that gender has any impact on response to psychotherapy. CONCLUSIONS: The review identified relatively few studies, so limiting our capacity to draw more than provisional conclusions. As some studies of response to antidepressant drugs have suggested differential gender response, such gender differences may then be expected to reflect biological influences rather than any general tendency for gender to influence response to therapy non specifically. PMID- 20580090 TI - Complement control protein factor H: the good, the bad, and the inadequate. AB - The complement system is an essential component of the innate immune system that participates in elimination of pathogens and altered host cells and comprises an essential link between the innate and adaptive immune system. Soluble and membrane-bound complement regulators protect cells and tissues from unintended complement-mediated injury. Complement factor H is a soluble complement regulator essential for controlling the alternative pathway in blood and on cell surfaces. Normal recognition of self-cell markers (i.e. polyanions) and C3b/C3d fragments is necessary for factor H function. Inadequate recognition of host cell surfaces by factor H due to mutations and polymorphisms have been associated with complement-mediated tissue damage and disease. On the other hand, unwanted recognition of pathogens and altered self-cells (i.e. cancer) by factor H is used as an immune evasion strategy. This review will focus on the current knowledge related to these versatile recognition properties of factor H. PMID- 20580096 TI - Prevalence and determinants of complicated grief in general population. AB - BACKGROUND: Few epidemiological studies have examined complicated grief in the general population, especially in Asian countries. Therefore, this study aimed to explore the prevalence and predictors of complicated grief among community dwelling individuals in Japan. METHODS: A questionnaire survey regarding grief and related issues was conducted on community dwelling individuals aged 40-79 who were randomly sampled from census tracts. Complicated grief was assessed using the Brief Grief Questionnaire. Stepwise logistic regression analysis was conducted in order to identify predictors of complicated grief. RESULTS: Data from 969 responses (response rate, 39.9%) were subjected to analysis. The analysis revealed 22 (2.4%) respondents with complicated grief and 272 (22.7%) with subthreshold complicated grief. Respondents who were found to be at a higher risk for developing complicated grief had lost their spouse, lost a loved one unexpectedly, lost a loved one due to stroke or cardiac disease, lost a loved one at a hospice, care facility or at home, or spent time with the deceased everyday in the last week of life. LIMITATIONS: Limitations of this study include the small sample size, the use of self-administered questionnaire, and the fact that the diagnoses of complicated grief were not based on robust diagnostic criteria. CONCLUSIONS: The point prevalence of complicated grief within 10years of bereavement was 2.4%. Complicated grief was maintained without significant decrease up to 10years after bereavement. When subthreshold complicated grief is included, the prevalence of complicated grief boosts up to a quarter of the sample, therefore, routine screening for complicated grief among the bereaved is desired. Clinicians should pay particular attention to the bereaved families with abovementioned risk factors in order to identify people at risk for future development of complicated grief. PMID- 20580097 TI - Takotsubo cardiomyopathy and elevated troponin levels following cerebral seizure. PMID- 20580095 TI - Glial and glutamatergic markers in depression, alcoholism, and their comorbidity. AB - BACKGROUND: Alteration of glutamatergic neurotransmission in the prefrontal cortex (PFC) may contribute to the pathophysiology of alcoholism and major depressive disorder (MDD). Among glial cells, astrocytes are mostly responsible for recycling synaptic glutamate by uptake through excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), and conversion to glutamine with glutamine synthetase (GS). Low density of astrocytes in the PFC of "uncomplicated' alcoholics and MDD subjects may parallel altered glutamate transporters and GS in the PFC. METHODS: Immunohistochemistry and Western blotting for glutamate transporters, GS and glial fibrillary acidic protein (GFAP) were applied to postmortem tissue of the left orbitofrontal cortex from 13 subjects with MDD, 13 with alcoholism, 10 with comorbid alcoholism plus MDD (MDA), and 13 non-psychiatric controls. Area fraction of immunoreactivity was measured in sections, and protein levels in Western blots. RESULTS: EAAT2 immunoreactivity was significantly lower in MDD and MDA subjects than in controls. EAAT1 levels were lower in MDA and MDD subjects as compared to controls, while GS levels in MDA were significantly lower than in alcoholics and controls, and lower in MDD subjects than in alcoholics. Area fraction of GFAP was lower in MDD, but not in MDA subjects as compared to controls or alcoholics. LIMITATIONS: High variability of protein levels in some groups and effects of antidepressant treatment, although appearing to be limited, cannot be fully evaluated. CONCLUSIONS: There are differential changes in the expression of glial glutamatergic markers in depression and alcoholism, suggesting a depletion of certain aspects of glutamatergic processing in depression. PMID- 20580098 TI - CA125 in heart failure: implications for immunoinflammatory activity. PMID- 20580099 TI - Atherosclerosis modulates the electrophysiological effects of a peroxisome proliferator-activated receptor-gamma activator on pulmonary veins. PMID- 20580100 TI - Heart rate in acute heart failure, lower is not always better. PMID- 20580101 TI - Comparative angioscopic evaluation of neointimal coverage and thrombus between TAXUS-Express and TAXUS-Liberte stents: is the stent platform type associated with the vascular response? PMID- 20580102 TI - Prognosis of mild/moderate chronic systolic heart failure. PMID- 20580103 TI - Clinical outcomes and prognostic factor for acute heart failure in nonagenarians: impact of hypoalbuminemia on mortality. PMID- 20580104 TI - Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease. AB - BACKGROUND: Abnormal cardiac autonomic nervous activity (CANA) is not uncommon in postoperative patients with congenital heart disease (CHD). METHODS AND RESULTS: We attempted to clarify the prognostic value of the CANA variables in postoperative CHD patients and prospectively evaluated the CANA variables in 292 consecutive biventricular and 91 Fontan repair patients. The CANA variables included the heart rate variability, arterial baroreflex sensitivity (BRS), washout ratio of the myocardial metaiodobenzylguanidine scintigraphy, and plasma norepinephrine level. With a follow-up of 10 +/- 2 years, 98 total events that required hospitalization, including 13 deaths and 48 unscheduled cardiac events (UCEs), occurred. In all the CHD patients, all the CANA indices predicted the total events and UCEs. Of those, the NE level (p=0.0004) and BRS (p=0.0373) predicted the mortality. In a multivariate analysis, the BRS was an independent CANA-predictor for the total events (p=0.007). In the biventricular patients, the plasma NE level, heart rate variability, and BRS predicted the total events and UCEs and the BRS was the only independent CANA-predictor for the total events (p=0.0329). In the Fontan patients, the plasma NE level was the only predictor for the UCEs (p=0.0242) and no other CANA variables were independent predictors of the total events or UCEs. CONCLUSIONS: All CANA variables, especially the BRS, were useful predictors for future clinical events in biventricular CHD patients, whereas no CANA variables, except for the plasma NE level, predicted future clinical events in the Fontan patients. PMID- 20580106 TI - CHADS2 score predicts time interval free of atrial fibrillation in patients with symptomatic paroxysmal atrial fibrillation. PMID- 20580107 TI - Alternative approach for selected severe pulmonary hypertension of congenital heart defect without initial correction--palliative surgical treatment. AB - OBJECTIVES: Uncorrected congenital heart defects (CHD) with severe pulmonary hypertension (sPH, systolic pulmonary artery>70% of systolic pressure) are usually considered inoperable. We are curious to know if some selected patients might benefit from palliative operation for those sPH with uncorrected CHD. METHODS: Adults or adolescents with sPH associated with ventricular septal defect (VSD) with/without great artery anomalies were selected for pulmonary artery banding (PAB) to reduce sPH. The target pulmonary pressure was less than half of the systolic blood pressure after arch or great arteries reconstruction. Repeated catheterization was performed to evaluate the feasibility of defect closure. RESULTS: Consecutively, 8 patients (age 26 +/- 9 years) received PAB as a palliative procedure in the past 8 years without mortality. The pre-PAB systolic pulmonary pressure was 119 +/- 9 mmHg. Additional PAB had been applied in 4 of them. All patients showed significant improvement in function class (III to I or II). The mean post-PAB pulmonary pressure decreased significantly (77.5 +/- 9.2 mmHg to 42.0 +/- 9.0 mmHg) and 6-minute walk test was also found to have great improvement (270 +/- 86 m to 414 +/- 49 m), but the saturation at rest did not show a difference. Three of them received corrective surgery to close defects over 3-5 years. CONCLUSION: For some selected adult sPH with uncorrected CHD, PAB can work as a palliative procedure to improve their functional class and even provide a chance of total repair. PMID- 20580105 TI - Cardiopulmonary exercise testing is equally prognostic in young, middle-aged and older individuals diagnosed with heart failure. AB - BACKGROUND: Previous research has demonstrated the prognostic value of cardiopulmonary exercise testing (CPX) in elderly patients with heart failure (HF). Investigations that have comprehensively examined the value of CPX across different age groups are lacking. The purpose of the present investigation was to evaluate the prognostic value of CPX in young, middle-aged and older patients with HF. METHODS: A total of 1605 subjects (age: 59.2 +/- 13.7 years, 78% male) underwent CPX and were subsequently tracked for major cardiac events. Ventilatory efficiency (VE/VCO(2) slope) and peak oxygen consumption (VO(2)), both absolute and percent-predicted, were determined. The prognostic value of these CPX variables was assessed in <= 45, 46-65 and >= 66 year subgroups. RESULTS: The three year event rates for major cardiac events in the <= 45, 46-65 and >= 66 year subgroups were 8.8%, 6.0% and 5.7%, respectively. The VE/VCO(2) slope (Hazard ratio >= 1.07, p<0.001), peak VO(2) (Hazard ratio <= 0.87, p<0.001) and percent-predicted peak VO(2) (Hazard ratio 0 <= 0.98, p<0.001) were all significant prognostic markers in each age subgroup. While the VE/VCO(2) slope carried the greatest prognostic strength, peak VO(2) and percent-predicted peak VO(2) were retained in multivariate analyses (Residual Chi-Square >= 5.2, p<0.05). With respect to peak VO(2), the actual value was the more robust prognostic marker in the <= 45 and >= 66 year subgroups while the percent predicted expression provided better predictive resolution in subjects who were 46-65 years old. CONCLUSIONS: These results indicate that, irrespective of a patient's age at presentation, CPX provides valuable prognostic information in the HF population. PMID- 20580108 TI - Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome. AB - INTRODUCTION: Iron deficiency is common in cyanotic congenital heart disease (CHD) and results in reduced exercise tolerance. Currently, iron replacement is advocated with limited evidence in cyanotic CHD. We investigated the safety and efficacy of iron replacement therapy in this population. METHODS: Twenty-five iron-deficient cyanotic CHD patients were prospectively studied between August 2008 and January 2009. Oral ferrous fumarate was titrated to a maximum dose of 200mg thrice-daily. The CAMPHOR QoL questionnaire, 6 minute walk test (6MWT) and cardiopulmonary exercise testing were conducted at baseline and after 3 months of treatment. RESULTS: Mean age was 39.9 +/- 10.9 years, 80% females. Fourteen had Eisenmenger syndrome, 6 complex cyanotic disease and 5 Fontan circulation. There were no adverse effects necessitating termination of treatment. After 3 months of treatment, hemoglobin (19.0 +/- 2.9 g/dL to 20.4 +/- 2.7 g/dL, p<0.001), ferritin (13.3 +/- 4.7 MUg/L to 54.1 +/- 24.2 MUg/L, p<0.001) and transferrin saturation (17.8 +/- 9.6% to 34.8 +/- 23.4%, p<0.001) significantly increased. Significant improvements were also detected in the total CAMPHOR score (20.7 +/- 10.9 to 16.2 +/- 10.4, p=0.001) and 6MWT distance (371.7 +/- 84.7 m to 402.8.0+/-74.9m, p=0.001). Peak VO(2) remained unchanged (40.7 +/- 9.2% to 43.8 +/- 12.4% of predicted, p=0.15). CONCLUSION: Three months of iron replacement therapy in iron deficient cyanotic CHD patients was safe and resulted in significant improvement in exercise tolerance and quality of life. Identification of iron deficiency and appropriate replacement should be advocated in these patients. PMID- 20580109 TI - Use of a Randomized Response Technique to obtain sensitive information on animal disease prevalence. AB - In order for policy-makers to formulate effective disease control measures they require accurate estimates of the extent and prevalence of the disease. On occasion, obtaining these data can be difficult, as farmers may perceive relevant information as being sensitive to divulge. Consequently, underestimation of disease prevalence may occur due to farmer reticence about admitting to behaviours and outcomes that are considered professionally transgressive. To overcome such weaknesses, this study used a novel social science survey method known as the Randomized Response Technique in order to obtain population level estimations of transgressionary behavior and disease prevalence for the case of sheep scab in Wales. Since deregulation in 1992, sheep scab has become widespread throughout the UK. Previous estimates of sheep scab in the UK have employed survey techniques which do not adequately protect the anonymity of the farmers' answers other than via verbal or institution backed promise. In this study, farmers at several agricultural shows in Wales were asked to complete questionnaires according to the Randomized Response Technique during the summer of 2009. The survey results suggest that 30% of farmers did not routinely treat their sheep for scab. A further 36.5% of the surveyed farmers admitted to having sheep scab in their flocks in the past 5 years. These estimates are both higher than obtained by previous surveys which used more traditional questionnaire structures. Survey responses revealed a strong willingness to reintroduce compulsory treatment measures to control or eradicate the disease. This is the first study to demonstrate the value of the Randomized Response Technique in the context of animal health. PMID- 20580110 TI - Mass spectrometric imaging of small molecules. AB - Small molecules are defined as low molecular weight organic compounds (typically <1000 Da), which could be either natural or artificial. Because established imaging methods are not able to selectively detect the positions, concentrations and structures of small molecules in biological samples, new methods have been developed. This review summarizes recent technological developments in one such method, mass spectrometric imaging (MSI). Lipids, hydrocarbons, sugars, phenolics, alkaloids, antibiotics, pharmaceutical and agrochemical compounds, bacterial, plant, and insect-defensive and semiochemical compounds are covered. Additionally, the latest MSI methods as well as sample preparation, imaging software, and medical and biological applications will be discussed. PMID- 20580111 TI - Evaluation of the 'dose of the day' for IMRT prostate cancer patients derived from portal dose measurements and cone-beam CT. AB - PURPOSE: High geometrical and dosimetrical accuracies are required for radiotherapy treatments where IMRT is applied in combination with narrow treatment margins in order to minimize dose delivery to normal tissues. As an overall check, we implemented a method for reconstruction of the actually delivered 3D dose distribution to the patient during a treatment fraction, i.e., the 'dose of the day'. In this article results on the clinical evaluation of this concept for a group of IMRT prostate cancer patients are presented. MATERIALS AND METHODS: The actual IMRT fluence maps delivered to a patient were derived from measured EPID-images acquired during treatment using a previously described iterative method. In addition, the patient geometry was obtained from in-room acquired cone-beam CT images. For dose calculation, a mapping of the Hounsfield Units from the planning CT was applied. With the fluence maps and the modified cone-beam CT the 'dose of the day' was calculated. The method was validated using phantom measurements and evaluated clinically for 10 prostate cancer patients in 4 or 5 fractions. RESULTS: The phantom measurements showed that the delivered dose could be reconstructed within 3%/3mm accuracy. For prostate cancer patients, the isocenter dose agreed within -0.4+/-1.0% (1 SD) with the planned value, while for on average 98.1% of the pixels within the 50% isodose surface the actually delivered dose agreed within 3% or 3mm with the planned dose. For most fractions, the dose coverage of the prostate volume was slightly deteriorated which was caused by small prostate rotations and small inaccuracies in fluence delivery. The dose that was delivered to the rectum remained within the constraints used during planning. However, for two patients a large degrading of the dose delivery was observed in two fractions. For one patient this was related to changes in rectum filling with respect to the planning CT and for the other to large intra fraction motion during treatment delivery, resulting in mean underdosages of 16% in the prostate volume. CONCLUSIONS: A method to accurately assess the 'dose of the day' was evaluated for prostate cancer patients treated with IMRT. To correct for observed dose deviations off-line dose-adaptive strategies will be developed. PMID- 20580112 TI - Effects of plantar cutaneo-muscular and tendon vibration on posture and balance during quiet and perturbed stance. AB - Modulation of lower limb somatosensory information by tendon or plantar vibration produces directionally specific, vibration-induced falling reactions that depend on the tendon or the region of the sole that is vibrated. This study characterized the effects of different patterns of plantar cutaneo-muscular vibration and bilateral Achilles tendon vibration (ATV) on the postural strategies observed during quiet and perturbed stance. Twelve healthy young participants stood barefooted, with their vision blocked, on two sets of plantar vibrators placed on two AMTI force plates embedded in a moveable support surface. Two other vibrators were positioned over the Achilles tendons. Participants were randomly exposed to different patterns of plantar cutaneo-muscular and ATV. Tilts of the support surface in the toes-up (TU) and toes-down (TD) directions were given 5-8s after the beginning of vibration. Body kinematics in 3D and ground reaction forces were recorded. Bilateral ATV applied with or without rearfoot vibration (RFV) during quiet stance resulted in a whole-body backward leaning accompanied by an increase in trunk extension and hip and knee flexion. RFV alone produced a forward whole-body tilt with increased flexion in trunk, hip, and ankle. When stance was perturbed by TU tilts, the center of mass (CoM) and center of pressure (CoP) displacements were larger in the presence of RFV or ATV and associated with increased peak trunk flexion. TD tilts with or without ATV resulted in no significant difference in CoM and CoP displacements, while larger trunk extension and smaller distal angular displacements were observed during ATV. RFV altered the magnitude of the balance reactions, as observed by an increase in CoP displacements and variable response in trunk displacement. Significant interactions between ATV and RFV were obtained for the peak angular excursions for both directions of perturbations, where ATV either enhanced (for TU tilts) or attenuated (for TD tilts) the influence of RFV. Manipulating somatosensory information from the plantar cutaneo-muscular and muscle spindle Ia afferents thus results in altered and widespread postural responses, as shown by profound changes in body kinematics and CoM and CoP displacements. This suggests that the CNS uses plantar cutaneo-muscular and ankle spindle afferent inputs to build an appropriate reference of verticality that influences the control of equilibrium during quiet and perturbed stance. PMID- 20580113 TI - The food glycome: a source of protection against pathogen colonization in the gastrointestinal tract. AB - Trillions of microbes inhabit the gastrointestinal tract of humans with significant differences in the composition and distribution of intestinal flora along its length. Normally there is a symbiotic relationship between the intestinal microflora and the host, with mutual advantages for both partners. When this relationship is altered, commensal bacteria can rapidly shift toward pathogenicity resulting in the onset and progression of gastrointestinal infection. Pathogen adhesion and colonization is often a prelude to infection, and intervention at this early stage can help prevent disease. Bacteria have evolved a multitude of adhesion mechanisms commonly targeting surface carbohydrate structures of the host. Here, we review the ability of various dietary carbohydrates to prevent adhesion of pathogens to host cells. Given their significance in disease, and their ability to cause chronic infection, we have focussed on 3 model pathogens, Helicobacter pylori, Campylobacter jejuni and Clostridium difficile, and dietary carbohydrates which can inhibit their adhesion. The discovery of novel anti-adhesive dietary carbohydrates, once developed as nutraceutical ingredients, may serve as a novel method for preventing infectious diseases in the human gastrointestinal tract. Anti-adhesive carbohydrates used in this context are not bactericidal. Therefore, the spread of pathogens with resistance to antibiotics is less likely to occur. PMID- 20580114 TI - Adaptive response of Lactobacillus sakei 23K during growth in the presence of meat extracts: a proteomic approach. AB - Lactobacillus sakei is a lactic acid bacterium mainly found in meat and meat products. In order to understand the factors favoring its adaptation to meat matrix, growth parameters and survival of the strain L. sakei 23K in the presence of sarcoplasmic or myofibrillar extracts were assessed. Cytosolic proteins putatively involved in the response of this strain to meat proteins were determined using 2D electrophoresis and the significantly regulated proteins were identified by Maldi Tof-MS analyses. From the 31 differentially expressed spots, 16 occurred in the presence of myofibrillar extract while 6 proteins were modulated by the sarcoplasmic extract. Two dipeptidases were overexpressed in the presence of sarcoplasmic proteins, in correlation to the protein degradation patterns obtained by SDS-PAGE. In the presence of the myofibrillar extract, L. sakei 23K overexpressed proteins related to energy and pyrimidine metabolism as well as ala- and tyr-tRNA synthetases, involved in translation, while others corresponding to general stress response, pyrimidine, vitamin and cofactor biosynthesis were down-regulated. The supplementary nutrients furnished by meat extracts modulated the overexpression of proteins related to translation, peptide/amino acid metabolism and energy production while the stress proteins were under regulated. The results obtained here suggest that meat proteins would not represent a stress environment per se for L. sakei 23K in contrast to the harsh conditions during meat processing. This study has extended the understanding of the molecular responses and growth mechanisms of L. sakei 23K in the presence of meat proteins. The transference of genomic information into useful biological insight is an important step for the selection of well-adapted strains for the achievement of high-quality fermented products. PMID- 20580116 TI - In the swim of things: recent insights to neurogenetic disorders from zebrafish. AB - The advantage of zebrafish as a model to study human pathologies lies in the ease of manipulating gene expression in vivo. Here we focus on recent progress in our understanding of motor neuron diseases and neurodevelopmental disorders and discuss how novel technologies will permit further disease models to be developed. Together these advances set the stage for this simple functional model, with particular advantages for transgenesis, multigenic analyses and chemical biology, to become uniquely suited for advancing the functional genomics of neurological and possibly psychiatric diseases - from understanding the genetics and cell biology of degenerative and developmental disorders to the discovery of therapeutics. PMID- 20580115 TI - Evolutionary genetics in wild primates: combining genetic approaches with field studies of natural populations. AB - Ecological and evolutionary studies of wild primates hold important keys to understanding both the shared characteristics of primate biology and the genetic and phenotypic differences that make specific lineages, including our own, unique. Although complementary genetic research on nonhuman primates has long been of interest, recent technological and methodological advances now enable functional and population genetic studies in an unprecedented manner. In the past several years, novel genetic data sets have revealed new information about the demographic history of primate populations and the genetics of adaptively important traits. In combination with the rich history of behavioral, ecological, and physiological work on natural primate populations, genetic approaches promise to provide a compelling picture of primate evolution in the past and in the present day. PMID- 20580117 TI - A Bayesian multilevel model for fMRI data analysis. AB - Bayesian approaches have been proposed by several functional magnetic resonance imaging (fMRI) researchers in order to overcome the fundamental limitations of the popular statistical parametric mapping method. However, the difficulties associated with subjective prior elicitation have prevented the widespread adoption of the Bayesian methodology by the neuroimaging community. In this paper, we present a Bayesian multilevel model for the analysis of brain fMRI data. The main idea is to consider that all the estimated group effects (fMRI activation patterns) are exchangeable. This means that all the collected voxel time series are considered manifestations of a few common underlying phenomena. In contradistinction to other Bayesian approaches, we think of the estimated activations as multivariate random draws from the same distribution without imposing specific prior spatial and/or temporal information for the interaction between voxels. Instead, a two-stage empirical Bayes prior approach is used to relate voxel regression equations through correlations between the regression coefficient vectors. The adaptive shrinkage properties of the Bayesian multilevel methodology are exploited to deal with spatial variations, and noise outliers. The characteristics of the proposed model are evaluated by considering its application to two real data sets. PMID- 20580119 TI - The diverse ontogeny and function of murine small intestinal dendritic cell/macrophage subsets. AB - Intestinal dendritic cell and macrophage subsets are believed to play key roles in maintaining intestinal homeostasis in the steady state and in driving protective immune responses in the setting of intestinal infection. This mini review focuses on recent progress regarding the ontogeny and function of small intestinal lamina propria dendritic cell/macrophage subsets. In particular we discuss recent findings suggesting that small intestinal CD103(+) dendritic cells and Cx3cr1(+) cells derive from distinct precursor populations and that CD103(+) dendritic cells represent the major migratory population of cells with a key role in initiating adaptive immune responses in the draining mesenteric lymph node. In contrast, Cx3cr1(+) cells appear to represent a tissue resident population, phenotypically indistinguishable from tissue resident macrophages. These latter observations suggest an important division of labour between dendritic cell/macrophage subsets in the regulation of intestinal immune responses in the steady state. PMID- 20580118 TI - A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients. AB - INTRODUCTION: Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. METHODS: A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. RESULTS: Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. CONCLUSIONS: The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m2 every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously. PMID- 20580120 TI - An advanced approach for the characterization of dendritic cell-induced T cell proliferation in situ. AB - It is commonly accepted that dendritic cells (DCs) play a pivotal role in the induction of adaptive T cell-mediated immune responses. The clonal expansion of antigen-specific T cells within secondary lymphoid organs reflects the efficiency of antigen processing and presentation by DCs. Consequently, the quantification of proliferating antigen-specific T cells represents an important read-out for analyzing DC-T cell interactions. Standard proliferation assays are usually performed with cell suspensions of antigen-stimulated lymphocytes labelled with carboxyfluorescein diacetate succinimidyl ester, [(3)H] thymidine, or 5-bromo-2 deoxyuridine. However, these assays have important limitations, including the complete loss of information about the localization of proliferating cells in situ. Additionally, the ex vivo stimulation with antigen does not necessarily reflect the in vivo situation of cell proliferation. Therefore, an advanced approach for a detailed characterization of proliferating T cells in situ would be helpful for the interpretation of ongoing adaptive immune responses. Here, we describe the development of a fluorescence-based multicolour assay allowing the characterization and quantification of proliferation in different T cell subtypes in cryosections of lymphoid organs. Our approach combines the major benefits of flow cytometry and immunofluorescent-based histology, such as (i) multicolour phenotyping of cell populations and (ii) description of tissue-specific sites of cell proliferation. PMID- 20580121 TI - Migration of dendritic cells from murine skeletal muscle. AB - To better understand the role of dendritic cells (DCs) in skeletal muscle, we investigated the migration of DCs from murine skeletal muscle and compared that to previously studied footpad (FP) DC trafficking. We adoptively transferred carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled mature DCs to syngeneic mice and followed them in various lymphatic tissues at different time points. Injection of DCs into the tibialis anterior muscle resulted in the peak number of CFSE(+) DCs recovered in spleen at 12h, not at 24h, when the largest number of these cells appeared in the draining lymph nodes. Interestingly, this result for adoptive transfer of DCs to skeletal muscle differs with what is previously reported for adoptive transfer to the FP, a result that we also confirmed in parallel studies. These findings could have a significant impact on (1) understanding muscle diseases with immunological complications such as muscular dystrophies and (2) the immunologic effects of treatments for muscle diseases. PMID- 20580122 TI - Enhanced tolerance to low temperature in tobacco by over-expression of a new maize protein phosphatase 2C, ZmPP2C2. AB - Low temperature is one of the most common environmental stresses affecting plant growth and agricultural production. Serine/threonine protein phosphatases 2C (PP2Cs) have been suggested to play an important role in stress signaling. To identify potential new member of the PP2C proteins in maize and investigate its functions for stress responses, the ZmPP2C2 gene, encoding a new PP2C protein from maize roots, was cloned by RT-PCR and RACE-PCR. Its constitutive expression in roots, stems and leaves of maize seedlings was detected by RNA gel blot, and its regulation in response to cold stress was also examined. To further evaluate its function in the cold stress response, we over-expressed the ZmPP2C2 gene in tobacco under the control of the Cauliflower Mosaic Virus (CaMV) 35S promoter, and assessed a series of physiological changes in wild type and transgenic plants under low temperatures. Compared with wild type tobacco under cold stress, plants that over-expressed ZmPP2C2 displayed higher germination speed and rate, higher antioxidant enzyme (SOD, POD, CAT) activities, with lower cold-induced electrolyte leakage and malondialdehyde (MDA) contents. These results show that over-expression of ZmPP2C2 in tobacco enhanced tolerance to cold stress, suggesting that this new gene, ZmPP2C2, may act as a positive regulator of cold resistance in plants. PMID- 20580123 TI - The photosensitive phs1 mutant is impaired in the riboflavin biogenesis pathway. AB - A photosensitive (phs1) mutant of Arabidopsis thaliana was isolated and characterized. The PHS1 gene was cloned using a map-based approach. The gene was found to encode a protein containing a deaminase-reductase domain that is involved in the riboflavin pathway. The phenotype and growth of the phs1 mutant were comparable to that of the wild-type when the plants were grown under low light conditions. When the light intensity was increased, the mutant was characterized by stunted growth and bleached leaves as well as a decrease in FNR activity. The NADPH levels declined, whereas the NADP(+) levels increased, leading to a decrease in the NADPH/NADP(+) ratio. The mutant suffered from severe photooxidative damage with an increase in antioxidant enzyme activity and a drastic reduction in the levels of chlorophyll and photosynthetic proteins. Supplementing the mutant with exogenous FAD rescued the photosensitive phenotype, even under increasing light intensity. The riboflavin pathway therefore plays an important role in protecting plants from photooxidative damage. PMID- 20580124 TI - Identification of putative target genes to manipulate Fe and Zn concentrations in rice grains. AB - Rice is the staple food of half of the world's population; however, it is a poor source of essential micronutrients such as Fe and Zn. Since flag leaves are one of the sources of remobilized metals for developing seeds, the identification of the molecular players that might contribute to the process of metal transport from flag leaves to the seeds may be useful for biofortification purposes. We analyzed the expression of 25 metal-related genes from rice, including rice homologues for YSLs, NRAMPs, ZIPs, IRT1, VIT1 (coding for known or potential metal transporters), as well as NASs, FROs and NAC5 (involved in metal homeostasis) in flag leaves of eight rice cultivars (showing contrasting levels of seed Fe and Zn) during panicle emergence (R3) and grain filling stage (R5). The expression level of nine of these genes (OsYSL6, OsYSL8, OsYSL14, OsNRAMP1, OsNRAMP7, OsNRAMP8, OsNAS1, OsFRO1 and OsNAC5) in flag leaves exhibited significant correlations with Fe and/or Zn concentrations in the seeds. In this way, our study has provided a short list of putative target genes to manipulate Fe and Zn concentrations in rice grains. PMID- 20580125 TI - Outbreak of carbapenem-resistant Acinetobacter baumannii among non-burn patients in a burn intensive care unit. PMID- 20580126 TI - Microbicidal effect of electrolysed detergent water. PMID- 20580127 TI - Effects of gastric acidity on peristomal infection after percutaneous endoscopic gastrostomy placement. AB - Peristomal infection is a common complication following percutaneous endoscopic gastrostomy (PEG) placement. This study investigated the effect of gastric acidity on peristomal infection, including type of bacteria and the relationship between bacteria cultured from the oropharynx and PEG tube site. Sixty-seven patients with dysphagia underwent PEG placement at Otaki Hospital between 1998 and 2001. Gastric acidity was evaluated by 24h pH monitoring. Patients were observed for peristomal infection for two weeks after PEG placement, with specimens collected from the oropharynx and PEG tube site. Twenty-one (31.3%) of the patients who had undergone PEG insertion developed peristomal infections. Of 52 patients who were not colonised with meticillin-resistant Staphylococcus aureus (MRSA) in the oropharynx, 11 cases (21.2%) developed peristomal infection. The median gastric pH of infected patients (11 cases) was 5.05+/-2.55 (mean+/-SD) and in patients without infection (41 cases) it was 3.06+/-1.83 (P=0.019). Peristomal infection developed in 66.7% (10/15) of patients carrying MRSA compared with only 21.2% (11/52) of patients who were not colonised by MRSA (P<0.001). The incidence of peristomal infection was affected by gastric acidity and the presence of MRSA in the oropharynx. PMID- 20580128 TI - The future of emergency medicine. PMID- 20580129 TI - Alzheimer's pathology in primary progressive aphasia. AB - Primary progressive aphasia (PPA) is a neurodegenerative disorder with language impairment as the primary feature. Different subtypes have been described and the 3 best characterized are progressive nonfluent aphasia (PNFA), semantic dementia (SD) and logopenic/phonological aphasia (LPA). Of these subtypes, LPA is most commonly associated with Alzheimer's disease (AD) pathology. However, the features of PPA associated with AD have not been fully defined. Here we retrospectively identified 14 patients with PPA and either pathologically confirmed AD or cerebrospinal fluid (CSF) biomarkers consistent with AD. Analysis of neurological and neuropsychological features revealed that all patients had a syndrome of LPA with relatively nonfluent spontaneous speech, phonemic errors, and reduced digit span; most patients also had impaired verbal episodic memory. Analysis of the pattern of cortical thinning in these patients revealed left posterior superior temporal, inferior parietal, medial temporal, and posterior cingulate involvement and in patients with more severe disease, increasing involvement of left anterior temporal and frontal cortices and right hemisphere areas in the temporo-parietal junction, posterior cingulate, and medial temporal lobe. We propose that LPA may be a "unihemispheric" presentation of AD, and discuss this concept in relation to accumulating evidence concerning language dysfunction in AD. PMID- 20580130 TI - Age-related neuronal loss in the cochlea is not delayed by synaptic modulation. AB - Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over- or underexpress neuregulin-1 (NRG1), a direct modulator of synaptic transmission. Transgenic mice overexpressing NRG1 in spiral ganglion neurons (SGNs) showed improvements in hearing thresholds, whereas NRG1 -/+ mice show a complementary worsening of thresholds. However, no significant change in age-related loss of SGNs in either NRG1 -/+ mice or mice overexpressing NRG1 was observed, while a negative association between NRG1 expression level and survival of inner hair cells during aging was observed. Subsequent studies provided evidence that modulating NRG1 levels changes synaptic transmission between SGNs and hair cells. One of the most dramatic examples of this was the reversal of lower hearing thresholds by "turning-off" NRG1 overexpression. These data demonstrate for the first time that synaptic modulation is unable to prevent age-related neuronal loss in the cochlea. PMID- 20580131 TI - Protein oxidation inhibits NO-mediated signaling pathway for synaptic plasticity. AB - Oxidative stress is a primary factor inducing brain dysfunction in aged animals. However, how oxidation affects brain function is not fully understood. Here we show that oxidation inhibits signaling pathways essential for synaptic plasticities in the cerebellum. We first revealed that nitric oxide (NO) dependent plasticities at the parallel fiber-Purkinje cell synapse (PF synapse) were impaired in the cerebellar slices from aged mice, suggesting a possible inhibitory action of protein oxidation by endogenous reactive oxygen species. PF synaptic plasticities were also blocked in the cerebellar slices from young mice preincubated with oxidizing agents or thiol blocker. Because the treatment of the slices with the oxidizing agent did not affect basic electrophysiological properties of excitatory postsynaptic current of PF (PF-EPSC) and did not occlude the synaptic plasticities, oxidation was revealed to specifically inhibit signaling pathways essential for PF-synaptic plasticities. Finally, biochemical analysis confirmed the idea that inhibitory action of protein oxidation on the PF synaptic plasticities was mediated by impairment of nitric oxide-induced protein S-nitrosylation. Therefore, oxidation was revealed to inhibit the S-nitrosylation dependent signaling pathway essential for synaptic plasticity in a "competitive" manner. PMID- 20580133 TI - [Fibrinolytic therapy for massive pulmonary thromboembolism in an elderly patient with left pneumonectomy receiving chemotherapy]. PMID- 20580134 TI - Co-infection with two emergent old pathogens: Trypanosoma cruzi and Helicobacter pylori. PMID- 20580135 TI - Influence of bulky 3,3'-diphenylalanine enantiomers replacing position 2 of AVP analogues on their conformations: NMR and molecular modeling studies. AB - In this paper we use NMR spectroscopy and molecular modeling to examine four vasopressin analogues substituted with bulky 3,3'-diphenylalanine (Dpa) enantiomers: [Mpa(1),Dpa(2),Val(4),D-Arg(8)]VP (I), [Mpa(1),D-Dpa(2),Val(4),D Arg(8)]VP (II), [D-Dpa(2),D-Arg(8)]VP (III) and [Mpa(1),D-Dpa(2)]AVP (IV). All the peptides exhibit a strong and prolonged antidiuretic activity. Additionally, analogues II, III and IV display antiuterotonic activity and analogue II is also a weak V(1a) receptor blocker. The conformational analysis has shown that beta turns at positions 2,3 and/or 3,4 are characteristic of OT antagonists. In turn, the beta-turn in the Cys(6)-Gly(9) fragment seems to be crucial for enhancement of the antidiuretic activity. The high accessibility of aromatic side chains at positions 2 and 3 plays a crucial role in antagonist-receptor binding. Moreover, orientation of the Phe(3) side chain is claimed to be important for V(1a) receptor affinity. PMID- 20580136 TI - Synthesis and biological evaluation of novel 2,4'-bis substituted diphenylamines as anticancer agents and potential epidermal growth factor receptor tyrosine kinase inhibitors. AB - Four new series of 2,4'-bis diphenylamine hydrazones 14, 2,4'-bis aminothiadiazole 16, 2,4'-bis mercaptotriazole 17-18 and 2,4'-bis mercapto oxadiazole diphenylamine derivatives 19-20 were synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase. Compound N-ethyl-5-{2-[4-(5 (ethylamino)-1,3,4-thiadiazol-2-yl)- phenylamino]phenyl}-1,3,4-thiadiazol-2-amine 16a was the most active enzyme inhibitor (98% inhibition at 10 microM). Moreover, all compounds that showed enzyme inhibition activity were tested in vitro on human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. The tested compounds exploited potent antitumor activity with IC(50) values ranging 0.73-2.38 microM. Molecular modeling and docking of the synthesized compounds into the active site of EGFR kinase domain showed good agreement with the obtained biological results. The present work represents a novel class of diphenylamine based derivatives with potent cytotoxicity and promising EGFR PTK inhibition activity. PMID- 20580132 TI - A PIN1 polymorphism that prevents its suppression by AP4 associates with delayed onset of Alzheimer's disease. AB - Alzheimer's disease (AD), the most common form of dementia, is characterized by the presence of neurofibrillary tangles composed of tau and senile plaques of amyloid-beta peptides (Abeta) derived from amyloid precursor protein (APP). Pin1 is a unique prolyl isomerase that has been shown to protect against age-dependent neurodegeneration by acting on phosphorylated tau and APP to suppress tangle formation and amyloidogenic APP processing. Here we report a functional polymorphism, rs2287839, in the Pin1 promoter that is significantly associated with a 3-year delay in the average age at onset (AAO) of late-onset AD in a Chinese population. More significantly, the Pin1 polymorphism rs2287839 is located within the consensus binding motif for the brain-selective transcription factor, AP4 (CAGCTG) and almost completely abolishes the ability of AP4 to bind and suppress the Pin1 promoter, as shown by chromatin immunoprecipitation, electrophoretic mobility shift assay, and promoter luciferase assay. Moreover, overexpression or knockdown of AP4 resulted in an 80% reduction or 2-fold increase in endogenous Pin1 levels, respectively. Thus, AP4 is a novel transcriptional repressor of Pin1 expression and the Pin1 promoter single nucleotide polymorphism (SNP) identified in this study that prevents such suppression is associated with delayed onset of AD. These results indicate that regulation of Pin1 by AP4 plays a critical role in determining age at onset of AD and might be a novel therapeutic target to delay the onset of AD. PMID- 20580137 TI - Structural characterization and antibacterial activity against clinical isolates of Staphylococcus of N-phenylamide of monensin A and its 1:1 complexes with monovalent cations. AB - The ability of N-phenylamide of monensin A (M-AM1) to form complexes with Li(+), Na(+) and K(+) cations is studied by ESI MS, (1)H and (13)C NMR, FT-IR spectroscopy and PM5 semi-empirical methods. ESI mass spectrometry indicates that M-AM1 forms complexes with the Li(+), Na(+) and K(+) cations of exclusively 1:1 stoichiometry which are stable up to cv = 90 V, and the formation of the complex with the Na(+) cation is strongly favoured. In the ESI MS spectra measured at cv = 110 V the fragmentation of the respective complexes, involving several dehydration steps, is observed. The spectroscopic studies show that the structures of M-AM1 and its complexes with Li(+), Na(+) and K(+) cations are stabilized by intramolecular hydrogen bonds in which OH groups are always involved. The CO amide group is shown to be engaged in the complexation process of each cation. However, there is a complex with K(+) cation in whose structure this CO amide group does not participate to a significant extent. The in vitro biological tests of M-AM1 amide have proved its good activity towards some strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin resistant S. aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). PMID- 20580138 TI - Identification of potent virtual leads to design novel indoleamine 2,3 dioxygenase inhibitors: pharmacophore modeling and molecular docking studies. AB - Indoleamine 2,3-dioxygenase, a heme-containing enzyme, is emerging as a vital target for the treatment of cancer, chronic viral infections, and other diseases. The aim of this study is to identify novel scaffolds and utilize them in designing potent IDO inhibitors. Pharmacophore hypotheses were developed. The highly correlating (r = 0.958) hypothesis with two hydrogen bond acceptor, one hydrogen bond donor and one hydrophobic aromatic features was selected, validated and used in virtual screening. Hit compounds were subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with critical active site amino acids were identified. These final hits may act as potent virtual leads in effective IDO inhibitor designing. PMID- 20580139 TI - Synthesis and docking studies of novel benzopyran-2-ones with anticancer activity. AB - Novel series of 7-substituted-benzopyran-2-ones was synthesized by incorporating heterocyclic rings as oxadiazole, triazole, pyrazole or pyrazolin-5-one to benzopyran-2-one nucleus at p-7 via methylene-oxy or acetoxy linker. In-vitro anticancer activity was evaluated for these hybrids; twelve compounds were selected by National Cancer Institute for anticancer screening. Among them, compound 9a exhibited broad spectrum antitumor activity showing full panel median growth inhibition (GI(50)) = 5.46 microM. According to docking results using Molsoft ICM 3.4-8c program, the target compounds may act through inhibition of topoismerase 1, where camptothecin is used as ligand. PMID- 20580140 TI - An analytical model for rotator cuff repairs. AB - BACKGROUND: Currently, natural and synthetic scaffolds are being explored as augmentation devices for rotator cuff repair. When used in this manner, these devices are believed to offer some degree of load sharing; however, no studies have quantified this effect. Furthermore, the manner in which loads on an augmented rotator cuff repair are distributed among the various components of the repair is not known, nor is the relative biomechanical importance of each component. The objectives of this study are to (1) develop quasi-static analytical models of simplified rotator cuff repairs, (2) validate the models, and (3) predict the degree of load sharing provided by an augmentation scaffold. METHODS: The individual components of the repair constructs were modeled as non linear springs, and the model equations were formulated based on the physics of springs in series and parallel. The model was validated and used to predict the degree of load sharing provided by a scaffold. Parametric sensitivity analysis was used to identify which of the component(s)/parameter(s) most influenced the mechanical behavior of the augmented repair models. FINDINGS: The validated models predict that load will be distributed approximately 70-80% to the tendon repair and approximately 20-30% to the augmentation component. The sensitivity analysis suggests that the greatest improvements in the force carrying capacity of a tendon repair may be achieved by improving the properties of the bone-suture tendon interface. Future studies will perform parametric simulation to illustrate the manner in which changes to the individual components of the repair, representing different surgical techniques and scaffold devices, may influence the biomechanics of the repair construct. PMID- 20580141 TI - Unemployment and self-rated health: neighborhood influence. AB - This work contributes to the study of the relationship between health, work and context by investigating the interaction between them in Brazil, a country with great social inequalities. It investigates whether unemployment and socioeconomic characteristics of the neighborhoods in which people live are associated with poor self-rated health after adjustment for individual sociodemographic characteristics, behavioral risk factors and health status. Moreover, it tests whether living in an area of socioeconomic deprivation modifies the association between unemployment and self-rated health. The study involved participants whose ages ranged from 15 up to 64 years, and who lived in four Brazilian cities included in the National Household Survey on Risk Behaviors and Reported Morbidity from Non-Communicable Diseases, carried out by the Ministry of Health in 2002/2003. Data from the 2000 Brazilian Population Census were used to calculate two neighborhood socioeconomic indicators: the proportion of householders with low income, a compositional variable of individual level characteristics, and residing in slums, a contextual variable not captured by individual properties. Logistic regression analysis was estimated by Generalized Estimating Equations. Of the 6426 participants, 20.6% reported poor self-rated health. Unemployment as well as residing in slums or in low income household areas were significantly associated with poor self-rated health. The magnitudes of these associations were attenuated after adjustment for sociodemographic characteristics, behavioral risk factors and other health status indicators. However, the association between unemployment and poor self-rated health was not modified by neighborhood socioeconomic indicators. Results confirm the association between unemployment and poor self-rated health, regardless of the personal or contextual characteristics studied here. Similarly, they show a clear independent association between self-rated health and neighborhood context. Even so, they do not show that the neighborhood contexts investigated modify the associations between unemployment and poor self-rated health. PMID- 20580142 TI - Ethical challenges in the provision of end-of-life care in Norwegian nursing homes. AB - As in other Western countries, most Norwegian nursing home patients are suffering from multi-pathological conditions and a large majority of them will die in the nursing home. End-of-life care represents many challenges, and it is a widespread concern that several nursing homes lack both resources and competence to ensure good quality care. This article examines the types and prevalence of ethical challenges in end-of-life care as nursing home staff consider them, as well as what they believe can help them to better cope with the ethical challenges. It is based on a national survey probing Norwegian nursing homes' end-of-life care at the ward level conducted in 2007. 664 respondents from 364 nursing homes answered the questionnaire, representing 68% of the patients and 76% of the nursing home sample. Inadequate care due to lack of resources and breaches of the patient's autonomy and integrity were the ethical challenges reported most often. Conflicts with the next of kin regarding nursing care and termination of life-prolonging treatment were reported more seldom. However, when asking the respondents to outline one of the most recent ethical dilemmas they had encountered, the majority of the respondents described ethical dilemmas concerning limitation of life-prolonging treatment, often mixed with disagreements between the wish of the family and that of the patient, or between the wish of the next of kin and what the staff consider to be right. Ethical dilemmas associated with breaches of the patient's autonomy and integrity were also thoroughly described. According to the staff, better ethical knowledge along with more time to reflect on ethical dilemmas were the initiatives most desired to improve the staff's way of handling ethical challenges. Furthermore, to have an opportunity to consult with a person holding ethical competence was emphasised by more than half of the respondents. PMID- 20580143 TI - 'Waiting until they got home': gender, smoking and tobacco exposure in households in Scotland. AB - The introduction in March 2006 of legislation banning smoking in public places in Scotland raised concerns that smokers would smoke more at home and so increase the exposure of those living with them to tobacco smoke. Drawing on interviews from two qualitative studies conducted after the implementation of the legislation, this article uses a gendered analysis to explore where and why smokers, who lived with non-smokers including children, continued to smoke in their homes. Although very few people attributed any increased home smoking to being a direct consequence of the legislation, many who already smoked there continued, and most women reported little or no disruption to their home smoking post-legislation. Also, because of the changing social environment of smoking, and other life circumstances, a minority of women had increased their levels of home smoking. Compared to the men in these studies, women, particularly those who didn't work outside the home, had restricted social lives and thus were less likely to have smoked in public places before the legislation and spent more time socialising in the homes of other people. In addition, women with children, including women who worked outside their homes, were more likely to spend sustained periods of time caring for children compared to fathers, who were more likely to leave the home to work or socialise. Although home smoking was linked to gendered caring responsibilities, other issues associated with being a smoker also meant that many women smokers chose to keep smoking in their homes. PMID- 20580144 TI - Tibiofibular synostosis--an unusual case during vascularized fibula flap harvest. PMID- 20580145 TI - Fine-needle aspiration cytology of salivary gland lesions: a systematic review. AB - PURPOSE: The aim of this study was to provide a systematic review of fine-needle aspiration (FNA) cytology on salivary gland lesions. MATERIALS AND METHODS: A review of the literature was carried out using PubMed, SCIRUS, and the Cochrane Central Register of Controlled Trials (CENTRAL). The present study included only data correlating cytological and histological diagnoses. RESULTS: Of the patients, 484 received a histological diagnosis of malignant tumor; cytological diagnosis was concordant in 387 (79.95%), discordant in 97 (20.04%). A total of 1,275 patients received a histological diagnosis of benign tumor; cytological diagnosis was concordant in 1,219 (95.608%) and discordant in 56 (4.39%). In all, 154 patients received a histological diagnosis of non-neoplastic lesion; cytological diagnosis was concordant in 145 (94.156%) and discordant in 9 (5.84%). CONCLUSION: FNA is a safe diagnostic tool that has a reliable sensitivity and specificity for the assessment of salivary gland pathology. FNA cytology may be useful in routine preoperative diagnostic testing. PMID- 20580146 TI - Immediate and delayed lateral ridge expansion technique in the atrophic posterior mandibular ridge. AB - PURPOSE: The lateral ridge expansion technique is used to expand the narrow edentulous ridge for implant placement. The staged approach can be used to split the mandibular ridge to decrease the risk of malfracture during osteotomy. The present study reports the clinical results of a surgical technique that expands a narrow mandibular ridge using an immediate and a delayed lateral expansion technique. MATERIALS AND METHODS: A total of 32 patients with a narrow edentulous posterior mandibular ridge of 2 to 4 mm were included in the present study, and 84 implants were placed. Of the 32 patients, 23 were treated with an immediate lateral expansion technique and 9 with a delayed lateral expansion technique. RESULTS: Of the 23 patients who underwent the immediate lateral expansion technique, a malfracture of the thin buccal cortical plate occurred during ridge splitting in 5 patients. All buccal segments of the 9 patients who underwent the delayed lateral expansion technique fractured as planned at the inferior horizontal corticotomy line favorably. After 4 to 5 months, all implants were stable and surrounded by bone, and ossification of the osteotomy line was obvious. CONCLUSIONS: The lateral ridge expansion technique is effective for horizontal augmentation in the severely atrophic posterior mandibular ridge. The delayed lateral ridge expansion technique can be used more safely and predictably in patients with high bone quality and thick cortex and a narrower ridge in the mandible. PMID- 20580147 TI - Augmentation in proximity to the incisive foramen to allow placement of endosseous implants: a case series. AB - PURPOSE: To assess whether augmentation in the proximity of the incisive foramen with an intraoral bone graft to allow for reliable placement of implants is achievable, not jeopardizing the nasopalatine nerve and vessels in a way causing patients' distress. PATIENTS AND METHODS: Five patients who had lost a central maxillary incisor due to trauma, and in whom a deficiency of bone at the palatal side was present in the proximity of the incisal canal, were augmented with autogenous cancellous bone harvested from the retromolar region. After a healing period of 3 months, implants were inserted. Patients' acceptance, complications, and postoperative morbidity of the procedure were prospectively evaluated by standardized clinical and radiographic examinations up to 12 months after augmentation. RESULTS: At the time of implant surgery, in all cases there was sufficient bone for insertion of the implants with adequate primary stability. Up to now (follow-up of 12-15 months) no fixtures have been lost and all peri implant tissues have a healthy appearance. All patients were satisfied. CONCLUSION: Augmentation in the proximity of the incisive foramen to enable implant placement appears to be feasible, both from the perspective of the patient and the professional. PMID- 20580148 TI - [The unpredictable behaviour of the solitary fibrous pleural tumour]. PMID- 20580149 TI - [Intrapulmonary Askin tumour: an unusual form of presentation]. PMID- 20580150 TI - An epidemiological survey of hymenoptera venom allergy in the Spanish paediatric population. AB - Hypersensitivity reactions to hymenoptera venom are infrequent in paediatric patients. A study was made to determine the incidence of this pathology in children, based on an epidemiological survey targeted to all members of the SEICAP (Sociedad Espanola de Inmunologia Clinica y Alergia Pediatrica/Spanish Society of Paediatric Clinical Immunology and Allergy), and designed to collect the data on patients under 17 years of age diagnosed with hymenoptera venom allergy. RESULTS: The data corresponding to 175 patients (135 males) were collected. The mean age was 9.9 +/- 3.6 years. Seventeen percent (32 patients) were the offspring of beekeepers, and 68.9% had experienced previous stings. The causal insect was Apis melifera, implicated in 55 cases, followed by Polistes dominulus (33 cases). In 151 patients (83.9%) the condition consisted of a local reaction. The most frequent systemic response was urticaria and angio-oedema. Fourteen patients suffered anaphylactic shock. The diagnosis was based on skin test (intradermal and prick) and/or specific IgE testing. Three treatment categories were established: (a) prevention and educational measures; (b) symptomatic treatment with oral antihistamines as well as self-injectable adrenalin; and (c) immunotherapy. In this context, 135 patients underwent immunotherapy with a mean duration of 3.5 +/- 1.7 years (range 2-5 years) - with excellent tolerance. The starting regimen was predominantly conventional (92 patients). CONCLUSIONS: The results of this survey show hypersensitivity reactions to hymenoptera venom to be infrequent in paediatrics, though with a strong impact upon patient quality of life. PMID- 20580151 TI - Laparoscopic ovarian tissue harvesting for cryopreservation: an effective and safe procedure for fertility preservation. AB - OBJECTIVE: To critically review our experience with the method of laparoscopic ovarian tissue harvesting for ovarian cryopreservation. STUDY DESIGN: In a retrospective cohort study 85 patients undergoing surgery for cryopreservation of ovarian tissue were included. One random ovarian cortical slice was histologically examined in order to determine the presence of primordial follicles and to detect possible malignant cells. Selective microbiological culture techniques from swabs were taken from all slices immediately after excision. Intra- and postoperative courses, histological and microbiological findings were evaluated. RESULTS: Eighty-five patients underwent cryopreservation of ovarian tissue, mostly for malignant diseases (78/85, 91.8%). Sixty patients (70.6%) underwent laparoscopy for ovarian tissue harvesting only, without any additional surgical procedure. The median operating time was 30 min (range 10-75 min). The intraoperative course was uneventful in these patients. In two patients slight postoperative increases in C-reactive protein levels were found. Microbiological examination revealed no contamination apart from one case revealing sporadic Propionibacterium acnes. Histological examination revealed intact ovarian tissue with primordial follicles in 81/85 patients (95.3%). CONCLUSION: Laparoscopy is a safe and effective procedure for ovarian tissue harvesting. We suggest microbiological and histological testing of ovarian tissue as mandatory tools to guarantee safety regarding ovarian tissue transplantation. PMID- 20580152 TI - Surface water and wastewater treatment using a new tannin-based coagulant. Pilot plant trials. AB - A new tannin-based coagulant-flocculant (Tanfloc) was tested for water treatment at a pilot plant level. Four types of water sample were treated: surface water (collected from a river), and municipal, textile industry (simulated by a 100 mg L(-1) aqueous solution of an acid dye), and laundry (simulated by a 50 mg L(-1) aqueous solution of an anionic surfactant) wastewaters. The pilot plant process consisted of coagulation, sedimentation, and filtration. The experiments were carried out with an average coagulant dosage of 92.2 mg L(-1) (except in the case of the surface water for which the dosage was 2 mg L(-1)). The efficacy of the water purification was notable in every case: total turbidity removal in the surface water and municipal wastewater, about 95% dye removal in the case of the textile industry wastewater, and about 80% surfactant removal in the laundry wastewater. Filtration improved the removal of suspended solids, both flocs and turbidity, and slightly improved the process as a whole. The efficiency of Tanfloc in these pilot studies was similar to or even better than that obtained in batch trials. PMID- 20580153 TI - Integrating objectives and scales for planning and implementing wetland restoration and creation in agricultural landscapes. AB - Traditionally, wetland management strategies have focused on single familiar objectives, such as improving water quality, strengthening biodiversity, and providing flood control. Despite the relevant amount of studies focused on wetland creation or restoration with these and other objectives, still little is known on how to integrate objectives of wetland creation or restoration at different landscape scales. We have reviewed the literature to this aim, and based on the existing current knowledge, we propose a four step approach to take decisions in wetland creation or restoration planning. First, based on local needs and limitations we should elucidate what the wetland is needed for. Second, the scale at which wetland should be created or restored must be defined. Third, conflicts and compatibilities between creation or restoration objectives must then be carefully studied. Fourth, a creation or restoration strategy must be defined. The strategy can be either creating different unipurpose wetlands or multipurpose wetlands, or combinations of them at different landscape scales. In any case, in unipurpose wetland projects we recommend to pursue additional secondary objectives. Following these guidelines, restored and created wetlands would have more ecological functions, similar to natural wetlands, especially if spatial distribution in the landscape is considered. Restored and created wetlands could then provide an array of integrated environmental services adapted to local ecological and social needs. PMID- 20580154 TI - Aqueous removal of diclofenac by plated elemental iron: bimetallic systems. AB - The aqueous removal of diclofenac (DF) by micrometric iron particles (Fe(0)) and amended Fe(0) (Me(0)(Fe(0))) under oxic and anoxic conditions was investigated. Bimetallic systems were obtained by plating the surface of Fe with Co, Cu, Ir, Ni, Pd and Sn. Experimental results confirmed the superiority of (Me(0)(Fe(0))) for DF removal except for IrFe (oxic) and SnFe (anoxic). Under anoxic conditions, Pd was by far the most efficient plating element followed by Ir, Ni, Cu, Co and Sn. However, under oxic conditions, Pd and Cu showed almost the same efficiency in removing DF followed by Ni, Co, Sn and Ir. Oxidative and reductive DF transformation products were identified under oxic and anoxic conditions respectively. In some systems (e.g. CoFe and SnFe oxic/anoxic; PdFe oxic; NiFe anoxic), no transformation products could be detected. This was ascribed to the nature of the plating element and its impact on the process of the formation of metal corrosion products (MCPs). MCPs are known for their high potential to strongly adsorb, bond, sequestrate and enmesh both the original contaminant and its reaction products. Obtained results corroborate the universal validity of the view, that aqueous contaminants are basically removed by adsorption and co precipitation. PMID- 20580155 TI - Man-made vitreous fiber produced from incinerator ash using the thermal plasma technique and application as reinforcement in concrete. AB - This study proposes using thermal plasma technology to treat municipal solid waste incinerator ashes. A feasible fiberization method was developed and applied to produce man-made vitreous fiber (MMVF) from plasma vitrified slag. MMVF were obtained through directly blending the oxide melt stream with high velocity compressed air. The basic technological characteristics of MMVF, including morphology, diameter, shot content, length and chemical resistance, are described in this work. Laboratory experiments were conducted on the fiber-reinforced concrete. The effects of fibrous content on compressive strength and flexural strength are presented. The experimental results showed the proper additive of MMVF in concrete can enhance its mechanical properties. MMVF products produced from incinerator ashes treated with the thermal plasma technique have great potential for reinforcement in concrete. PMID- 20580156 TI - Disposal of olive oil mill wastes in evaporation ponds: effects on soil properties. AB - The most common practice followed in the Med countries for the management of olive oil mill wastes (OMW) involves disposal in evaporation ponds or direct disposal on soil. So far there is lack of reliable information regarding the long term effects of OMW application on soils. This study assesses the effects of OMW disposal in evaporation ponds on underlying soil properties in the wider disposal site as well as the impacts of untreated OMW application on agricultural soils. In case of active disposal sites, the carbonate content in most soils was decreased, whereas soil EC, as well as Cl(-), SO(4)(2-), PO(4)(3-), NH(4)(+) and particularly K(+) concentrations were substantially increased. Soil pH was only marginally affected. Phenol, total N, available P and PO(4)(3-) concentrations were considerably higher in the upper soil layers in areas adjacent to the ponds. Available B as well as DTPA extractable Cu, Mn, Zn and Fe increased substantially. Most surface soil parameters exhibited increased values at the inactive site 6 years after mill closure and cease of OMW disposal activities but differences were diminished in deeper layers. It is therefore concluded that long term uncontrolled disposal of raw OMW on soils may affect soil properties and subsequently enhance the risk for groundwater contamination. PMID- 20580157 TI - Characteristics of organosulphur compounds adsorption onto Jordanian zeolitic tuff from diesel fuel. AB - The removal of organosulphur compounds (ORS) from diesel fuel is an important aspect of Jordanian's effort to reduce air pollution. Currently, the total sulphur content in Jordanian diesel fuel is 12,000 ppmw (1.2%, wt/wt), but Jordanian government has recently introduced new restrictions that will reduce this level gradually to internationally acceptable levels. The zeolitic tuff (ZT), from Tlul Al-Shahba region, was characterised using various analytical techniques. It was found that the Freundlich model fitted the adsorption isotherms more accurately than the Langmuir model; indicating that the ZT had a heterogeneous surface. The Langmuir adsorption capacity values for the three particle size ranges (100-200), (300-400), and (500-600) microm were 7.15, 6.32, and 5.52 mg/g and the column capacities were 4.45, 2.57, and 1.92 mg/g, respectively. The spent ZT was regenerated by washing with n-heptane with an efficiency of 81.5%. Two adsorption mechanisms were investigated. One is that the interaction of thiophene with the Bronsted site of the ZT through S atoms; the other is via C-S bond cleavage in thiophene-derived carbocations to form unsaturated fragments on the Bronsted acid sites. PMID- 20580158 TI - As(III) removal using an iron-impregnated chitosan sorbent. AB - An iron-impregnated chitosan granular adsorbent was newly developed to evaluate its ability to remove arsenic from water. Since most existing arsenic removal technologies are effective in removing As(V) (arsenate), this study focused on As(III). The adsorption behavior of As(III) onto the iron-impregnated chitosan absorbent was examined by conducting batch and column studies. Maximum adsorption capacity reached 6.48 mg g(-1) at pH=8 with initial As(III) concentration of 1007 microg L(-1). The adsorption isotherm data fit well with the Freundlich model. Seven hundred and sixty eight (768) empty bed volumes (EBV) of 308 microg L(-1) of As(III) solution were treated in column experiments. These are higher than the empty bed volumes (EBV) treated using iron-chitosan composites as reported by previous researchers. The investigation has indicated that the iron-impregnated chitosan is a very promising material for As(III) removal from water. PMID- 20580159 TI - Studies of thermodynamic properties and relative stability of a series of polyfluorinated dibenzo-p-dioxins by density functional theory. AB - The thermodynamic properties of 75 polyfluorinated dibenzo-p-dioxins (PFDDs) in the ideal gas state at 298.15K and 1.013x10(5) Pa have been calculated at the B3LYP/6-311G* level using Gaussian 03 program. The isodesmic reactions were designed to calculate standard enthalpy of formation (DeltaH(f)(degrees)) and standard free energy of formation (DeltaG(f)(degrees)) of PFDDs congeners. The relations of these thermodynamic parameters with the number and position of fluorine atom substitution (N(PFS)) were discussed, and it was found that there exist high correlations between thermodynamic parameters (entropy (S(degrees)), DeltaH(f)(degrees) and DeltaG(f)(degrees)) and N(PFS). According to the relative magnitude of their DeltaG(f)(degrees), the relative stability order of PFDD congeners was theoretically proposed. PMID- 20580160 TI - Recycling of automobile shredder residue with a microwave pyrolysis combined with high temperature steam gasification. AB - Presently, there is a growing need for handling automobile shredder residues--ASR or "car fluff". One of the most promising methods of treatment ASR is pyrolysis. Apart of obvious benefits of pyrolysis: energy and metals recovery, there is serious concern about the residues generated from that process needing to be recycled. Unfortunately, not much work has been reported providing a solution for treatment the wastes after pyrolysis. This work proposes a new system based on a two-staged process. The ASR was primarily treated by microwave pyrolysis and later the liquid and solid products become the feedstock for the high temperature gasification process. The system development is supported within experimental results conducted in a lab-scale, batch-type reactor at the Royal Institute of Technology (KTH). The heating rate, mass loss, gas composition, LHV and gas yield of producer gas vs. residence time are reported for the steam temperature of 1173 K. The sample input was 10 g and the steam flow rate was 0.65 kg/h. The conversion reached 99% for liquids and 45-55% for solids, dependently from the fraction. The H(2):CO mol/mol ratio varied from 1.72 solids and 1.4 for liquid, respectively. The average LHV of generated gas was 15.8 MJ/Nm(3) for liquids and 15 MJ/Nm(3) for solids fuels. PMID- 20580161 TI - Graphene oxide/ferric hydroxide composites for efficient arsenate removal from drinking water. AB - A series of novel composites based on graphene oxide (GO) cross-linked with ferric hydroxide was developed for effective removal of arsenate from contaminated drinking water. GO, which was used as a supporting matrix here, was firstly treated with ferrous sulfate. Then, the ferrous compound cross-linked with GO was in situ oxidized to ferric compound by hydrogen peroxide, followed by treating with ammonium hydroxide. The morphology and composition of the composites were analyzed by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The ferric hydroxide was found to be homogenously impregnated onto GO sheets in amorphous form. These composites were evaluated as absorbents for arsenate removal from contaminated drinking water. For the water with arsenate concentration at 51.14 ppm, more than 95% of arsenate was absorbed by composite GO-Fe-5 with an absorption capacity of 23.78 mg arsenate/g of composite. Effective arsenate removal occurred in a wide range of pH from 4 to 9. However, the efficiency of arsenate removal was decreased when pH was increased to higher than 8. PMID- 20580163 TI - Second-line chemotherapy for small-cell lung cancer (SCLC). AB - Although small-cell lung cancer (SCLC) generally shows an excellent response to initial chemotherapy, most patients finally relapse and salvage chemotherapy is considered. Usually, the response to salvage chemotherapy significantly differs between sensitive and refractory relapse. Sensitive relapse is relatively chemosensitive and re-challenge with the same drugs as used in the initial chemotherapy has been used historically, while refractory relapse is extremely chemo-resistant and its prognosis has been abysmal. To date, a number of clinical trials have been carried out for relapsed SCLC; however, the number of randomized trials is quite limited. At present, topotecan is the only drug approved by the US Food and Drug Administration for relapsed SCLC, and is considered the standard second-line chemotherapy in many countries. More recently, amrubicin has also shown more favorable antitumor activity, and is the most promising at present. Unfortunately, targeted agents have failed to demonstrate effectiveness for SCLC. Better understanding of the molecular mechanisms is clearly needed. PMID- 20580162 TI - Babesia microti-like infections are prevalent in North American foxes. AB - Babesia microti-like organisms have recently been identified as a cause of hemolytic anemia and azotemia in European dogs. A genetically and morphologically similar B. microti-like parasite has been identified in two foxes from North America. In order to assess the prevalence of this parasite in North American wild canids we screened blood samples from coyotes (Canis latrans) and red foxes (Vulpes vulpes) from eastern Canada and red foxes and gray foxes (Urocyon cinereoargenteus) from North Carolina, USA for the presence B. microti-like DNA by polymerase chain reaction. Thirty-nine percent (50/127) of the red fox samples, 26% (8/31) of the gray fox samples and none (0/12) from the coyote samples tested positive for the presence of B. microti-like DNA. Partial 18S ribosomal ribonucleic acid and beta-tubulin genes from the North American B. microti-like parasites of foxes were sequenced and samples from six domestic dogs from Spain that were infected with a B. microti-like parasite were analyzed for comparison. Partial 18S ribosomal ribonucleic acid and beta-tubulin gene sequences from the North American B. microti-like parasites of foxes were nearly identical to those previously reported from foxes as well as those from domestic dogs from Spain characterized in this study. Interestingly, partial beta-tubulin gene sequences characterized from the B. microti-like parasites of domestic dogs from Spain in this study were different from those previously reported from a Spanish domestic dog sample which is believed to be a pseudogene. The ability of the North American B. microti-like parasite to infect and induce disease in domestic dogs remains unknown. Further studies investigating the pathogenic potential of the North American B. microti-like parasite in domestic dogs are indicated. PMID- 20580164 TI - Long-lasting cognitive deficit induced by stress is alleviated by acute administration of antidepressants. AB - Deficits in executive control associated with frontal lobe dysfunction have been reported in affective disorder, which is often precipitated by stressful life events. Here we examined the impact of repeated restraint stress (1h daily for 7 days) on rats' performance in the attentional set-shifting task (ASST). To evaluate the persistence of cognitive deficits, the performance of separate groups of rats was assessed on the 4th, 7th, 14th and 21st day following stress cessation. Stressed rats exhibited unusually long-lasting extra-dimensional (ED) set-shifting impairments, since these deficits were demonstrated even 3 weeks following stress termination. An inhibitor of corticosterone synthesis, the drug metyrapone (50mg/kg, IP) protected rats from the cognitive impairment suggesting an involvement of endogenous adrenal steroids in the debilitating effects of stress. Acute intraperitoneal administration of four different antidepressants (desipramine, nomifensine, fluoxetine and escitalopram) at the minimum effective doses of 3, 0.3, 1 and 1mg/kg, respectively, reversed the deficits of ED set shifting in stressed animals. Desipramine, nomifensine, fluoxetine and escitalopram at the minimum effective doses of 6, 1, 1 and 1mg/kg, IP, respectively, promoted also cognitive flexibility in unstressed groups. We conclude that stress-induced long-term set-shifting impairment may represent a useful model mimicking clinically relevant aspects of depression, i.e., the persistence of executive dysfunction. The potential utility of antidepressants in treating frontal-like cognitive impairments is suggested. PMID- 20580165 TI - Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs. AB - The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon. PMID- 20580166 TI - Effect of protein-xanthophylls (PX) concentrate of alfalfa supplementation on physico-chemical properties of turkey breast and thigh muscles during ageing. AB - The objective was to evaluate the effects of a dietary protein-xanthophylls (PX) concentrate of alfalfa to turkey diets (at 15 and 30 g kg(-1) feed) on the physico-chemical properties of breast and thigh muscles during ageing. The experiment involved 120 turkeys (Big-6 type) allotted to 3 groups (group I control group; group II--with 1.5% supplementation of the protein-xanthophylls (PX) concentrate; group III--with 3% supplementation of the protein-xanthophylls (PX) concentrate). Measurements of pH, water holding capacity, color, oxymyoglobin content, TBARS and oxidation-reduction potential showed that the addition of protein-xanthophylls (PX) concentrate of alfalfa to a turkey diet did not cause deterioration of breast and thigh meat quality. In addition, changes in color, oxymyoglobin content, TBARS and oxidation-reduction potential values suggested that the inclusion of the concentrate to turkey diets acts as an antioxidant in the raw meat. PMID- 20580167 TI - Hepatitis B virus: from diagnosis to treatment. AB - During the next few decades, vaccination against hepatitis B virus (HBV) will dramatically change the epidemiological profile of this worldwide infection especially when Heath Policies encourage including HBV vaccination program for the newborns. However, it is still estimated that more than 2000millions living people have met HBV. Symptomatic hepatitis with jaundice is less frequent than asymptomatic infection; however, as much as 350millions of individuals remain chronically infected by HBV. In these cases, the need for efficient antiviral therapy remains clear when a viral replication is observed to control the risk of progression and the need for liver transplantation, which represents the only end stage treatment. Indeed, patients having chronic hepatitis B (CHB) can now be successfully treated using nucleos(t)ide analogs (NA) or pegylated interferon (PEG-IFN). Therefore, beside vaccination, prevention of the progression of the disease to cirrhosis and liver decompensation, leading to end-stage liver disease and/or to hepatocellular carcinoma, by inhibiting viral replication seems to represent the best approach to improve survival. At last but not least, co morbidities and other viral infections, leading also to chronic liver cirrhosis or liver inflammation such as the specific satellite delta virus (HDV), human immunodeficency virus (HIV) and/or hepatitis C (HCV) virus, are able to accelerate the progression and have to be taken in account. Interestingly, in treated infection, the dogma of the irreversibility of the liver fibrosis, when the cirrhosis is constituted, is tumbling down. In this review, we will focus on the clinical, virological and therapeutic aspects of hepatitis B infection in order to expose the proposals to follow-up and treat HBV-infected patients and the prevention of drug-resistant HBV mutants that frequently arise, leading to treatment failure and progression to liver disease. PMID- 20580169 TI - Molecular investigation of the occurrence of Coxiella burnetii in wildlife and ticks in an endemic area. AB - At present few studies have been carried out on the distribution and incidence of Coxiella burnetii infection in wildlife. Therefore, the aim of this study was to investigate the distribution of C. burnetii in the main wild species in the Basque Country (Northern Spain), such as carnivores, cervids, wild boar, lagomorphs and several species of birds. Tissues from a total of 601 animals and 340 adult ticks collected from them were analyzed by PCR. DNA of C. burnetii was detected in 5.1% of roe deer (Capreolus capreolus), 4.3% of wild boar (Sus scrofa), 9.1% of European hare (Lepus europaeus), and among wild birds, in 11% of vultures (Gyps fulvus) and 14% of black kites (Milvus migrans). These results showed that C. burnetii circulates in wildlife in Spain participating in the cycle of Q fever in nature. All of the adult ticks analyzed were negative for C. burnetii, suggesting that ticks do not play an important role in the transmission of C. burnetii in this area. PMID- 20580168 TI - Subtypes of nonmedical opioid users: results from the national epidemiologic survey on alcohol and related conditions. AB - AIMS: To identify subtypes of nonmedical opioid users, gender variations in psychiatric disorders, and quality of life in a representative sample of adults. METHODS: Analyses of data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N=43,093). Latent class analysis (LCA) and multinomial logistic regression procedures examined subtypes of nonmedical opioid users. RESULTS: Approximately 5% (n=1815) of adults used nonmedical opioids. LCA identified four subtypes: opioid-marijuana users (33%), opioid-other prescription drug users (9%), opioid-marijuana-hallucinogen users (28%), and opioid-polydrug users (30%). Subtypes were distinguished by race/ethnicity, gender, familial substance abuse, personal history of substance abuse treatment, and patterns of psychiatric disorders. Whites and men had increased odds of being in the opioid polydrug and opioid-marijuana-hallucinogen subtypes. The opioid-other prescription drug use subtype had disproportionately affected women who were characterized by high rates of mood/anxiety disorders and low quality of life. Across all subtypes, women and men had similarly problematic substance use disorders; however, women had more major depression and disability in the mental health domain. CONCLUSIONS: The generally high prevalence of psychiatric disorders among nonmedical opioid users, particularly women, underscores the need for comprehensive assessment and coordinated delivery of services to match needs with treatment, as well as continued monitoring of trends in opioid use and related problems. PMID- 20580170 TI - Isolation and characterisation of equine influenza viruses (H3N8) from Europe and North America from 2008 to 2009. AB - Like other influenza A viruses, equine influenza virus undergoes antigenic drift. It is therefore essential that surveillance is carried out to ensure that recommended strains for inclusion in vaccines are kept up to date. Here we report antigenic and genetic characterisation carried out on equine influenza virus strains isolated in North America and Europe over a 2-year period from 2008 to 2009. Nasopharyngeal swabs were taken from equines showing acute clinical signs and submitted to diagnostic laboratories for testing and virus isolation in eggs. The sequence of the HA1 portion of the viral haemagglutinin was determined for each strain. Where possible, sequence was determined directly from swab material as well as from virus isolated in eggs. In Europe, 20 viruses were isolated from 15 sporadic outbreaks and 5 viruses were isolated from North America. All of the European and North American viruses were characterised as members of the Florida sublineage, with similarity to A/eq/Lincolnshire/1/07 (clade 1) or A/eq/Richmond/1/07 (clade 2). Antigenic characterisation by haemagglutination inhibition assay indicated that the two clades could be readily distinguished and there were also at least seven amino acid differences between them. The selection of vaccine strains for 2010 by the expert surveillance panel have taken these differences into account and it is now recommended that representatives of both Florida clade 1 and clade 2 are included in vaccines. PMID- 20580171 TI - Tinnitus and cochlear implants. AB - OBJECTIVE: Several published studies seem to confirm the clinical observation that cochlear implants (CI) have a suppressive effect on tinnitus in most CI users. The aim of this paper is to present our personal experiences on tinnitus improvement after cochlear implantation. METHODS: Before surgery, 51 post lingually profoundly deaf adults, who underwent cochlear implantation between 2005 and 2007, filled out a questionnaire reporting tinnitus characteristics and the Italian version of the Tinnitus Handicap Inventory (THI-I). Moreover, they were asked to scale tinnitus loudness and annoyance. Six months after implant activation, patients repeated the same evaluations. Scores were statistically analysed by means of a Wilcoxon signed ranks test on the hypothesis that a CI could change the tinnitus magnitude and/or its annoyance. RESULTS: In our series of 36 patients, 36.10% reported total loudness suppression and another 41.6% reported a reduction. Annoyance scores reduced in 75% of patients. THI reduced in 72.2% of patients. CONCLUSION: Tinnitus reduction after CI may manifest as several mechanisms, such as habituation, acoustic masking, direct electrical nerve stimulation and cortical reorganization. Nevertheless, it is our opinion that data on CI benefits on tinnitus should be interpreted with caution and it seems reasonable to admit that further data is still necessary before considering CI as a treatment of tinnitus especially in unilateral deafness. PMID- 20580172 TI - A case of apogeotropic nystagmus with brainstem lesion: An implication for mechanism of central apogeotropic nystagmus. AB - We report a case showing apogeotropic nystagmus with the lesion of the brain stem, and discuss a possible mechanism of central apogeotropic nystagmus. The case was a 73-year-old male. We analyzed his nystagmus three-dimensionally. He showed apogeotropic nystagmus. Axis angles of slow phase eye velocity of his apogeotropic nystagmus were not in line with the axes perpendicular to the plane of horizontal semicircular canals, but with the patient's vertical axis. We then found that his nystagmus including the apogeotropic nystagmus was positioning, but not positional and that the direction of his positioning nystagmus was the same direction of postrotatory nystagmus after his head movement. His MRI scans showed an infarction around the prepositus hypoglossi nucleus of the brain. His apogeotropic nystagmus seemed to consist of a combination of prolonged postrotatory nystagmus after his head rotation to the left and right lateral position because the axis of postrotatory nystamus was in line with the axis of the head rotation. Therefore, it is suggested that a possible mechanism of central apogeotropic nystagmus is a prolonged postrotatory nystagmus after his head movement in the supine position due to the brain lesion involving the velocity storage mechanisms. PMID- 20580173 TI - Atypical carcinoid of the larynx and expressions of proteins associated with molecular targeted therapy. AB - OBJECTIVE: We reported an extremely rare case of atypical laryngeal carcinoid, and examined the expression of several proteins for application of molecular targeted therapy. METHOD: Case report and review of the literature concerning atypical carcinoid arising from the larynx. The expressions of proteins were determined by immunohistochemical analysis. RESULTS: We present here a case of atypical laryngeal carcinoid in a 79-year-old Japanese man, which was completely resected, and with no evidence of recurrence. On immunohistochemical analysis, neoplastic elements revealed, strong positivity for platelet-derived growth factor receptor alpha (PDGFRalpha), vascular endothelial growth factor receptor 2 (VEGFR2), and epidermal growth factor receptor (EGFR), and were mild positivity for KIT. CONCLUSION: Our findings suggest that atypical laryngeal carcinoid could be completely removed if it is located in the limited lesion. PDGFRalpha, VEGFR2, and EGFR expressions in this case provide the evidence that atypical laryngeal carcinoid is the candidate for molecular targeted therapy, although further investigations are necessary. PMID- 20580174 TI - [Transhepatic embolization of a hepatic artery aneurysm following laparoscopic cholecystectomy]. AB - Vascular complications following laparoscopic cholecystectomy are less frequent but carry higher morbidity than bile ducts lesions. We report on a 19-year-old patient, who presented a ruptured pseudoaneurysm of the hepatic artery 2 months after laparoscopic cholecystectomy. This case illustrates the alternative of direct transhepatic puncture with exclusive glue embolization in case of endovascular access failure. PMID- 20580175 TI - ActiTest accuracy for the assessment of histological activity grades in patients with chronic hepatitis C, an overview using Obuchowski measure. AB - BACKGROUND: ActiTest (AT) is a biomarker of liver necro-inflammatory histological activity validated in patients with chronic hepatitis C (HCV). AIM: The aim was to assess the accuracy of AT in comparison with alanine aminotransferase (ALT) the standard of care. METHODS: Methods used an integrated database of individual data and the new recommended Obuchowski measures. An updated "classical" meta analysis of AT validation studies was also performed. The main end points were the area under the ROC curves (AUROCs) for the diagnosis of each histological activity grade defined using METAVIR scoring system. To avoid repeated tests and the spectrum effect of activity grades prevalence, the comparison of AT and ALT accuracies used the Obuchowski method. RESULTS: For the individual analysis, a total of 1250 patients were included and for the meta-analysis six studies (2017 patients) were included. The overall accuracy of AT for the diagnosis of any activity grade (Obuchowski measure=0.850) was significantly higher than the accuracy of ALT (Obuchowski measure=0.837; P=0.009). The updated standard meta analysis confirmed the accuracy of AT (p<0.0001) both in independent AUROC=0.79 (95% CI, 0.73-0.85) and in non independent studies AUROC=0.74 (95% CI, 0.67 0.81). CONCLUSIONS: The accuracy of AT for grading the necro-inflammatory activity of patients with HCV was significantly higher than ALT serum activity alone, the standard biomarker. PMID- 20580176 TI - Linking human beta retrovirus infection with primary biliary cirrhosis. AB - Several environmental agents have been linked with primary biliary cirrhosis (PBC) that include bacteria, xenobiotics and viruses. A human beta retrovirus (HBRV) related to mouse mammary tumor virus has been cloned and characterized from patients with PBC. This agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and RT-PCR. The HBRV has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convincing evidence of beta retrovirus infection in patients. Three lines of evidence support a role for the virus in PBC. First, the beta retrovirus is linked with aberrant expression of mitochondrial protein(s) on the biliary epithelium cell (BEC) surface, a disease specific phenotype. Second, the related agent, mouse mammary tumor virus has been linked with autoimmune biliary disease in the NOD.c3c4 mouse model for PBC. In this mouse model, the virus is localized to diseased biliary epithelium that also display aberrant expression of the mitochondrial autoantigens. In translational studies, both patients with PBC and NOD.c3c4 mice demonstrate significant improvement in biliary disease with combination antiviral therapy. An overview of the biological relevance of the beta retrovirus infection in PBC will be discussed in this review. PMID- 20580177 TI - Retroperitoneal ganglioneuroma in children: CT and MRI features with histologic correlation. AB - OBJECTIVE: To demonstrate the CT and MRI features with histologic correlation of retroperitoneal ganglioneuromas in children. METHODS: The diagnostic images (seventeen CT scans and five MR scans) in 17 children with retroperitoneal ganglioneuroma confirmed by operation and histopathology were retrospectively reviewed, and correlated to the histologic findings. RESULTS: All tumors presented as an oval-shaped, well-defined mass on both CT and MR images. On unenhanced CT images, calcification was detected in six masses (35.3%), and predominantly low attenuation with the CT value ranged from 22 to 38 HU (mean 29.5 HU) in all the tumors. The tumors with CT value less than 30 HU had a relatively larger amount of myxoid stroma on histopathologic sections than those with CT value more than 30 HU. Tumors showed homogeneous low signal intensity on T1-weighted images and inhomogeneous high signal intensity with interlaced or nodular low signal intensity on T2-weighted images. The post-contrast enhancement on both CT and MR images was lacking or slight in early phase, but moderate or marked in late phase. The inhomogeneous high signal intensity on T2WI, as well as the delayed enhancement corresponded to a large amount of myxoid stroma and a relatively small number of cellular components in tumors. CONCLUSION: An oval shape, well-defined margin, low attenuation on CT, inhomogeneous hyperintensity on T2WI, and delayed moderate or marked enhancement are typical features of retroperitoneal ganglioneuroma in children. The imaging features correlated well to the histologic findings. PMID- 20580178 TI - Ileal Crohn's disease: MRI with endoscopic correlation. AB - PURPOSE: To evaluate activity staging of Crohn's disease (CD) measured with MR enterography using ileoscopy as reference standard. MATERIALS AND METHODS: A prospective study was made of 61 patients with CD. All patients underwent MR enterography and ileoscopy. MRI activity was measured by means of an ad hoc developed score, as well as by analysis of the imaging findings, and was compared with the SES-CD score obtained via ileoscopy. Examinations were performed using a 1.0 T scanner. RESULTS: MRI score discriminates between active and inactive disease with an area under the ROC curve of 0.941. Overall correlation with the standard reference SES-CD score was moderate to strong (Spearman's r=0.62 p<0.001). Agreement between both methods in staging patients with ileal CD as inactive, mild or moderate to severe was good (Cohen's kappa=0.60). Differences in means of the MRI activity scores of the three groups showed statistical significance (p<0.01). CONCLUSIONS: The MRI score is a reliable predictor of activity in ileal CD and can stage patients in a way comparable to endoscopy. 1.0 T scans are valid for performing radiological evaluation of ileal Crohn's disease. PMID- 20580179 TI - Diffusion and perfusion of the kidney. AB - MRI of the kidney currently makes the transition from depiction of morphology to assessment of function. Functional renal imaging methods provide information on diffusion and perfusion on a microstructural level. This review article presents the current status of functional renal imaging with focus on DWI (diffusion weighted imaging) and DCE-MRI (dynamic contrast-enhanced MRI), as well as BOLD (blood-oxygenation level dependent) MRI, DTI (diffusion tensor imaging) and arterial spin labeling (ASL). Technical background of these techniques is explained and clinical assessment of renal function, parenchymal disease, transplant function and solid masses is discussed. PMID- 20580180 TI - IHE profiles applied to regional PACS. AB - PACS has been widely adopted as an image storage solution that perfectly fits the radiology department workflow and that can be easily extended to other hospital departments. Integrations with other hospital systems, like the Radiology Information System, the Hospital Information System and the Electronic Patient Record are fully achieved but still challenging aims. PACS also creates the perfect environment for teleradiology and teleworking setups. One step further is the regional PACS concept where different hospitals or health care enterprises share the images in an integrated Electronic Patient Record. Among the different solutions available to share images between different hospitals IHE (Integrating the Healthcare Enterprise) organization presents the Cross Enterprise Document Sharing profile (XDS) which allows sharing images from different hospitals even if they have different PACS vendors. Adopting XDS has multiple advantages, images do not need to be duplicated in a central archive to be shared among the different healthcare enterprises, they only need to be indexed and published in a central document registry. In the XDS profile IHE defines the mechanisms to publish and index the images in the central document registry. It also defines the mechanisms that each hospital will use to retrieve those images regardless on the Hospital PACS they are stored. PMID- 20580181 TI - Determination of quinolizidine alkaloids in different Lupinus species by NACE using UV and MS detection. AB - Lupin seeds are important for animal and human nutrition. However, they may contain toxic quinolizidine alkaloids (QA). Analytical methods for a reliable alkaloid determination are therefore of importance. Here the presented study reports on the first CE method for the analysis of QA in Lupinus species. A buffer system consisting of 100mM ammonium formate in methanol, acetonitrile, and small amounts of water and acetic acid enabled the baseline separation of sparteine, lupanine, angustifoline and 13alpha-hydroxylupanine in less than 10min. Applied voltage, temperature and detection wavelength were 25kV, 30 degrees C and 210nm, respectively. Additional compounds were identified in CE-MS experiments, in which all alkaloids could be assigned in positive ESI mode at corresponding [M+H](+) values. The CE method was validated for linearity, sensitivity, accuracy and precision, and then used to assess the seeds of seven different Lupinus species for their alkaloid content. Lupanine was present in all of them within a range from 0.02% (L. densiflorus, L. microcarpus) to 1.47% (L. albus). The highest percentage of an individual alkaloid was found in L. polyphyllus (3.28% of angustifoline), the content of total alkaloids ranged from 0.43% (L. microcarpus) to 5.13% in L. polyphyllus. The quantitative results were in good agreement with literature data. PMID- 20580182 TI - Determination of molecular weight of hyaluronic acid by near-infrared spectroscopy. AB - This paper attempted the feasibility to determine the molecular weight of hyaluronic acid with near-infrared (NIR) diffuse reflectance spectroscopy. In this work, 46 experimental samples of hyaluronic acid powder were analyzed by partial least square (PLS) regression multivariate calibration method in the selected region of NIR spectra. The leave-one-out cross-validation method was used for the PLS model selection criterion. The accuracy of the final model was evaluated according to correlation coefficient of prediction set (Rp) and root mean square error of prediction set (RMSEP). The repeatability was verified through repeated measurement of spectra coupled with an appropriate chi-square test. Finally, the optimal calibration model was obtained with Rp=0.9814 and RMSEP=88.32 when using Savitzky-Golay first (SG-1st) derivative with 9 smoothing points spectral preprocessing method. The parameters above and repeatability of NIR spectroscopy obtained from chi-square test were both within the range of permissible error in factories. This study demonstrated that NIR spectroscopy was superior to conventional methods for the fast determination of molecular weight of hyaluronic acid. PMID- 20580183 TI - Kenyan patients' attitudes regarding doctor ethnicity and doctor-patient ethnic discordance. AB - OBJECTIVE: This study explored Kenyan patients' perspectives on the role of ethnicity in the doctor-patient relationship. METHODS: 221 participants completed questionnaires on ethnicity in doctor-patient relationships; eight focus groups were held with low- and middle-income urban and rural women. RESULTS: About half of participants expressed no preference for doctor ethnicity. Participants rated demographic factors as less important than factors related to the doctor's qualifications, communication skills, and cost of service. Those who did indicate a preference were more likely to prefer Indian doctors for eye problems and Europeans for major surgery, cancer, and heart problems. With less severe medical issues participants were more likely to prefer a doctor who was ethnically concordant with them. Reasons for this centered around communication issues. In contrast, several focus group participants did not want to be treated by doctors from their own ethnic group because of concerns about confidentiality. CONCLUSION: Additional research is needed on negative implications of patient provider concordance. PRACTICE IMPLICATIONS: Medical service providers must be aware of concerns about ethnic concordance. Alternatively medical centers that deal with sensitive medical information need to consider hiring staff who are not of the majority ethnic group in their region. PMID- 20580184 TI - Correlation between drugs of abuse and alcohol by hair analysis: parents at risk for having children with fetal alcohol spectrum disorder. AB - The fatty acid ethyl esters (FAEEs) hair test, a biomarker of excessive alcohol exposure, has demonstrated its potential for use in fetal alcohol spectrum disorder (FASD) diagnosis. FASD may be compounded by polydrug exposure. Our objective was to determine the likelihood of positive FAEE test among parents testing positive for other drugs of abuse. Samples submitted for FAEE hair analysis by Children's Aid Societies between October 2005 and May 2007, also concurrently tested for cocaine, cannabinoids, opiates, methamphetamine, amphetamine, benzodiazepines, methadone, and/or oxycodone, were included in our analysis. Subjects consisted of parents suspected of using excessive amounts of alcohol. Parents testing positive for drugs of abuse had a significantly increased risk for testing positive for high FAEE. Mothers testing positive for heavy chronic alcohol use were found to have a threefold increased risk of testing positive for cocaine (odds ratio=3.26, 1.1-9.7). Our results suggest that parents abusing stimulants are at risk of high alcohol exposure, which put their unborn children at risk for FASD. PMID- 20580185 TI - [Usefulness of lipidic solution for the treatment of systemic toxicity related to bupivacaine injected in a sub-coracoid brachial plexus block]. PMID- 20580186 TI - [Cardiac arrest at induction of a patient with thyrotoxicosis. Have you thought of anaphylaxis?]. AB - We report the occurrence of cardiac arrest shortly after the anaesthetic induction for thyroidectomy in a patient with decompensated thyrotoxicosis associated with taking amiodarone. After investigation, it was revealed that the cardiac arrest was linked to an anaphylactic reaction to suxamethonium. This accident, unrelated to hyperthyroidism, reminds us of the relative frequency and severity of anaphylactic reactions related to curare. This event, in the context of severe cardiac insufficiency, due to an amiodarone-associated thyrotoxicosis, is described here for the first time. Its diagnosis requires to remain consistent. Its support must be in compliance with the recommendations of learned societies of anaesthesia. PMID- 20580187 TI - Cardiovascular complications in patients with pheochromocytoma: a mini-review. AB - Phaeochromocytomas are rare neuroendocrine tumours secreting high levels of catecholamines, able to exert serious metabolic and cardiovascular effects. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines, especially noradrenaline, the main transmitter released from sympathetic nerve terminals. Hypertension, tachycardia, pallor, headache and anxiety, usually dominate the clinical presentation. Occasionally, patients with predominantly epinephrine-secreting tumours present hypotension or even shock. Other cardiovascular complications of pheochromocytoma include ischaemic heart disease, acute myocardial infarction, cardiac arrhythmias, heart failure due to toxic cardiomyopathy, or pulmonary edema. Catecholamines have been shown to influence the extracellular matrix with collagen deposition and subsequent fibrosis in the arterial wall and in the myocardium. These morphofunctional changes of the myocardium and of arterial wall can be emphasized by ultrasound imaging. Indeed, ultrasound imaging of the myocardium and arterial wall not only identifies wall thickness but also contains information on texture that may be revealed by acoustic tissue characterization. The latter can be quantified through videodensitometric analysis of echographic images or through ultrasonic integrated backscatter signal analysis. This paper reviews cardiovascular complications in patients with pheochromocytoma and utility of the new ultrasound technique as backscatter signal. It is useful for evaluating preclinical pathological morphofunctional changes of the myocardium and arterial wall, characterized by increased collagen content in pheochromocytoma patients. The recognition of early catecholamine-induced alterations in patients with pheochromocytoma, is important to prevent at least morbidity and mortality, before surgical treatment. PMID- 20580189 TI - Caution required when using an intraoperative knee balancer in total knee arthroplasty. AB - Various knee balancers have been developed to assist surgeons in balancing the flexion and extension spaces during total knee arthroplasty. Devices typically are designed to measure the distance between spaces during total knee arthroplasty at a given force level. We analyzed the accuracy of one type of these devices. We found that the devices accurately measure distances, but are quite inaccurate at demonstrating reproducible forces. PMID- 20580190 TI - Thirty-year follow-up of patient with Gorham disease (massive osteolysis) treated with hip arthroplasty. AB - Gorham disease (also known as massive osteolysis or disappearing bone disease) is an exceedingly rare, peculiar entity of uncertain cause and unpredictable prognosis. There is no proven mode of therapy or consensus on treatment. We present 30-year follow-up on a patient successfully treated with resection, total hip arthroplasty, and radiation with no recurrence of disease. Our observations in this case suggest that surgical treatment and reconstruction can lead to good long-term function and disease-free survival. PMID- 20580191 TI - Reduction in narcotic use after primary total knee arthroplasty and association with patient pain relief and satisfaction. AB - We examined the prevalence of narcotic use before and after total knee arthroplasty (TKA) and its association with post-TKA pain relief and satisfaction. Data on 6364 primary, unilateral TKA patients in a national registry were analyzed. Before TKA, 24% of patients were prescribed one form of narcotic. Of these, 14% reported continued narcotic use at 12 months after TKA, whereas the majority discontinued use. Only 3% of patients who did not use narcotics before TKA had a narcotics prescription at 12 months. Patients who used narcotics before TKA were more likely to have a narcotic prescription at 12 months post-TKA, reported greater pain at 12 months, and were more likely to be dissatisfied with TKA outcome. These findings have implications for patient pre TKA counseling. PMID- 20580192 TI - Prevalence and management of obstructive sleep apnea in patients undergoing total joint arthroplasty. AB - Obstructive sleep apnea (OSA) may be a risk factor for complications after total joint arthroplasty (TJA). We sought to determine the prevalence of OSA in patients undergoing TJA, and the safety and effectiveness of intrathecal narcotic (IN) in these patients. We retrospectively reviewed 1255 consecutive patients undergoing 1463 TJA at one hospital. All patients underwent routine screening for OSA and IN anesthesia, with 109 patients (134 TJA) identified with OSA (8.7%). Compared with 127 randomly selected patients (141 TJA) without OSA, OSA patients were significantly heavier and had higher American Society of Anesthesiologists scores, more comorbidities, longer length of stay, more transient hypoxia, more transfusions, and more medical variances. Despite more minor variances, with appropriate screening and management, OSA patients did not have a higher rate of significant or major complications. Length of stay, although longer, was only 2.3 days in OSA patients, demonstrating the safety and efficacy of IN anesthesia in these patients. PMID- 20580193 TI - Ceramic-on-ceramic hip outcome at a 5- to 10-year interval: has it lived up to its expectations? AB - This study reports revision and complication rates of a single cementless double wedged tapered stem with an alumina-alumina bearing over 10 years since the beginning of premarket clinical trials. Of 930 hips (848 patients) implanted by 9 surgeons, there were 19 revisions at mean follow-up of 5.9 years compared to 10 revisions in the 123 hips implanted with the polyethylene control group at mean 7.8 years. The ongoing safety of alumina-alumina bearings is demonstrated through excellent (96.8%) survivorship at 10 years. Twenty-one patients reported 23 incidences of noise described as clicking, squeaking, popping, or creaking. Eight patients with 9 hips described the noise as squeaking, most occurring rarely and only 1 occurring frequently in a patient subsequently revised for a reason aside from the squeaking. PMID- 20580194 TI - The use of navigation to obtain rectangular flexion and extension gaps during primary total knee arthroplasty and midterm clinical results. AB - The authors evaluated 112 knees treated by total knee arthroplasty (TKA) using a navigation-assisted modified gap balancing technique. Initial mediolateral gap differences in extension and in 90 degrees of flexion were measured after proximal tibia bone cutting. Final flexion and extension gaps were measured by checking distances under equal tension before prosthesis insertion. Amount of femoral bone cutting and external rotations of femoral components were found to depend on initial gaps. Patients with a final rectangular gap had greater knee flexion angles preoperatively and at 1 year after TKA. However, no differences were observed between the clinical and radiologic outcomes of knees with rectangular and nonrectangular gaps at 1 or 4 years after TKA. The study shows that the navigation-assisted modified gap balancing technique provides an effective means of achieving rectangular flexion and extension gaps during TKA. PMID- 20580195 TI - Is deep vein thrombosis a good proxy for pulmonary embolus? AB - It is assumed that prevention of deep venous thrombosis (DVT) is likely to lead to a reduction in the incidence of pulmonary embolus (PE). This study examines the association between symptomatic DVT and PE in patients undergoing orthopedic procedures. We reviewed medical records of 1495 patients who underwent evaluation for DVT or PE within 90 days of an index orthopedic procedure at our institution between 2004 and 2008. Only 27 cases were positive for both DVT and PE (1.7% of the total cohort, 10.8% of cases scanned for both DVT and PE). Tests of association, performed across the entire cohort and within specific subsets of patients, did not demonstrate that patients were more likely to have both DVT and PE than to have either DVT or PE. The high association between DVT and PE that is assumed to exist does not seem to hold true for orthopedic surgery patients. PMID- 20580196 TI - Current practice patterns in primary hip and knee arthroplasty among members of the American Association of Hip and Knee Surgeons. AB - A poll was conducted at the 2009 Annual Meeting of the American Association of Hip and Knee Surgeons to determine current practices among its members in primary total hip arthroplasty and total knee arthroplasty. This article summarizes the audience responses to a number of multiple choice questions concerning perioperative management and operative practice patterns and preferences including anesthetic choices, blood management, surgical approaches, implant selection, implant fixation, bearing surface choice, postoperative rehabilitation, recommended postoperative activity restrictions, and antibiotic prophylaxis. PMID- 20580198 TI - Arterial injury in total knee arthroplasty. AB - Arterial complications associated with knee arthroplasty are relatively rare, although probably underreported, complications of knee arthroplasty that carry a risk of significant morbidity. Thorough preoperative assessment and close liaison with a vascular surgeon, combined with an appreciation of common anatomical variants or distorted anatomy, may help prevent both thromboembolic and direct injuries from occurring. Clinical features of arterial complications following knee arthroplasty may vary significantly from acute hemorrhage or ischemia in the immediate postoperative period to chronic pain and swelling presenting even months following the procedure. There is potential for diagnostic confusion and delay that may adversely affect outcome. Early diagnosis along with vascular surgical review and intervention is key to successful management. PMID- 20580197 TI - Variability in physician opinions about the indications for knee arthroplasty. AB - To determine how much of variability in physician opinion about the indications for knee arthroplasty is due to inconsistency in individual physicians' opinions. We surveyed 201 orthopedic surgeons, 141 rheumatologists, and 455 family physicians. Physicians were asked how 34 patient characteristics affected their decision to perform or refer for knee arthroplasty. Surgeons and referring physicians agreed on how 4 and 2 of 34 patient characteristics affected their decision about knee arthroplasty, respectively. Half of the variability in opinion among physicians could be accounted for by inconsistency in their individual responses to the survey 6 weeks apart (mean intraclass correlation coefficient = 0.49). Although surgeons and referring physicians vary in their opinion, half of the variability could be attributed to individual physician inconsistency. PMID- 20580199 TI - Brain autopsy findings in intensive care unit patients previously suffering from delirium: a pilot study. AB - PURPOSE: Delirium affects 50% to 80% of intensive care unit (ICU) patients and is associated with increased risk of mortality. Given the paucity of data reporting the neuropathologic findings in ICU patients experiencing delirium, the purpose of this pilot, hypothesis-generating study was to evaluate brain autopsies in ICU patients who suffered from delirium to explore possible neuroanatomical correlates. MATERIALS AND METHODS: Using delirium databases at Vanderbilt University, we identified patients who had delirium in the ICU and subsequently died and received a brain autopsy during the same hospitalization. Brain autopsy reports were collected retrospectively on all 7 patients who met these criteria. RESULTS: Patients' mean age was 55 (SD +/- 8.4) years, and median number of days spent with delirium was 7 (+/- 5 interquartile range). In 6 (86%) of 7 patients, pathologic lesions normally attributed to hypoxia or ischemia were noted in the hippocampus, pons, and striatum. Hippocampal lesions represented the most common neuropathologic site of injury, present in 5 (71%) of 7 patients. CONCLUSIONS: Hypoxic ischemic injury in multiple locations of the brain was a common finding. The biological plausibility of hippocampal lesions as a contributor to long-term cognitive impairment warrants postmortem investigation on a larger scale with comparison to patients not experiencing ICU delirium. PMID- 20580200 TI - Symptoms in the month before death for stage 5 chronic kidney disease patients managed without dialysis. AB - CONTEXT: There is little evidence on the symptoms experienced by those with advanced (Stage 5) chronic kidney disease (CKD), managed without dialysis, as they approach death. As palliative care extends to noncancer illnesses, understanding symptom prevalence and severity close to death will clarify which symptom interventions are most needed and which elements of (largely cancer driven) models of palliative care best translate into end-of-life care for this population. OBJECTIVES: To determine symptom prevalence and severity in the last month of life for patients with Stage 5 CKD, managed without dialysis. METHODS: Longitudinal symptom survey in three U.K. renal units, using the patient completed Memorial Symptom Assessment Scale-Short Form (MSAS-SF). We calculated the prevalence of individual symptoms (with 95% confidence intervals [CI] to reflect sample size), plus MSAS-SF subscales, in the month before death. Comparison is made with previously published data on symptoms in the last month of life in advanced cancer, also measured using the MSAS-SF. RESULTS: Seventy four patients (mean age: 81 years; standard deviation [SD]: 6.8) were recruited (response rate: 73%); 49 (66%) died during follow-up (mean age: 81 years; SD: 5.7). "Month before death" symptom data were available for 43 (88%) of the 49 participants who died. Median time of data collection was 18 days from death (interquartile range: 12-26 days). More than half had lack of energy (86%; 95% CI: 73%-94%), itch (84%; 70%-93%), drowsiness (82%; 68%-91%), dyspnea (80%; 66% 90%), poor concentration (76%; 61%-87%), pain (73%; 59%-85%), poor appetite (71%; 57%-83%), swelling arms/legs (71%; 57%-83%), dry mouth (69%; 55%-82%), constipation (65%; 50%-78%), and nausea (59%; 44%-73%). Levels of distress correspond to prevalence, with the exception of dyspnea, which was disproportionately more distressing. The median number of symptoms reported was 16.6 (range: 6-27), rising to 20.4 (range: 7-34) if additional renal symptoms were included. On average, psychological distress was moderate (mean MSAS-PSYCH: 1.55) but with wide variation (SD: 0.50; range: 0.17-2.40), suggesting diverse levels of individual distress. The prevalence of both physical and psychological symptoms and the number reported were higher than those in advanced cancer patients in the month before death. CONCLUSION: Stage 5 CKD patients have clinically important physical and psychological symptom burdens in the last month of life, similar or greater than those in advanced cancer patients. Symptoms must be addressed through routine symptom assessment, appropriate interventions, and with pertinent models of end-of-life care. PMID- 20580202 TI - Aberrant drug-related behavior observed during clinical studies involving patients taking chronic opioid therapy for persistent pain and fentanyl buccal tablet for breakthrough pain. AB - CONTEXT: Information on aberrant drug-related behaviors in the clinical study setting is limited. OBJECTIVES: This retrospective analysis was designed to identify the types and frequency of aberrant drug-related behaviors (including misuse and abuse) and associated patient characteristics in opioid-tolerant patients with chronic pain. METHODS: Data from opioid-tolerant patients participating in clinical studies of fentanyl buccal tablet (FBT) for breakthrough pain (up to 18 months of clinical study case-report forms) were retrospectively reviewed and coded for abuse, overdose, and aberrant behavior. Aberrant behaviors were categorized as those involving FBT (overuse, lost or stolen study drug) and those not involving FBT (patients seeking prescriptions from other sources, not returning for follow-up). RESULTS: Of the 1,160 patients evaluated, 10 (<1%) patients had an abuse-related event, 18 (<2%) had a positive urine drug screening (nonprescribed drug or illicit substance), and 12 (1%) had an event consistent with opioid overdose; 124 (11%) had aberrant behaviors related to FBT, and 68 (6%) had aberrant behaviors that were not. Aberrant behaviors were more frequent in men (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1, 2.1; P<0.01), in patients 42 years or younger (OR: 2.5; 95% CI: 1.6, 4.0; P<0.01), and in patients 43 years to 49 years (OR: 1.9; 95% CI: 1.2, 3.1; P<0.01). CONCLUSION: The incidence of drug abuse events and aberrant drug-related behaviors was relatively low, probably because of the implementation of universal precautions and the controlled clinical study setting. Even in this setting, events occurred, highlighting the limits of screening and the need for ongoing monitoring of aberrant behavior. PMID- 20580201 TI - The association of depression and pain with health-related quality of life, disability, and health care use in cancer patients. AB - CONTEXT: Pain and depression are two of the most prevalent and treatable cancer related symptoms, each present in at least 20%-30% of oncology patients. OBJECTIVE: To determine the associations of pain and depression with health related quality of life (HRQL), disability, and health care use in cancer patients. METHODS: The Indiana Cancer Pain and Depression study is a randomized clinical trial comparing telecare management vs. usual care for patients with cancer-related pain and/or clinically significant depression. In this article, baseline data on patients enrolled from 16 urban or rural community-based oncology practices are analyzed to test the associations of pain and depression with HRQL, disability, and health care use. RESULTS: Of the 405 participants, 32% had depression only, 24% pain only, and 44% both depression and pain. The average Hopkins Symptom Checklist 20-item depression score in the 309 depressed participants was 1.64 (on 0-4 scale), and the average Brief Pain Inventory (BPI) severity score in the 274 participants with pain was 5.2 (on 0-10 scale), representing at least moderate levels of symptom severity. Symptom-specific disability was high, with participants reporting an average of 16.8 of the past 28 days (i.e., 60% of their days in the past four weeks) in which they were either confined to bed (5.6 days) or had to reduce their usual activities by 50% (11.2 days) because of pain or depression. Moreover, 176 (43%) participants reported being unable to work because of health-related reasons. Depression and pain had both individual and additive adverse associations with quality of life. Most patients were currently not receiving care from a mental health or pain specialist. CONCLUSION: Depression and pain are prevalent and disabling across a wide range of types and phases of cancer, commonly co-occur, and have additive adverse effects. Enhanced detection and management of this disabling symptom dyad is warranted. PMID- 20580203 TI - Antipsychotic drug side effects for persons with intellectual disability. AB - Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the Matson Evaluation of Side Effects (MEDS), the Abnormal Inventory Movement Scale (AIMS), and Dyskinesia Identification System Condensed User Scale (DISCUS) are reviewed. Symptom patterns and a focus on additional research are discussed. While progress has been made, more and more systematic methods to research these problems are necessary. PMID- 20580204 TI - T cell vaccination induces the elimination of EAE effector T cells: analysis using GFP-transduced, encephalitogenic T cells. AB - T cell vaccination (TCV) with irradiated encephalitogenic T cells induces resistance to EAE. However, the fate of the encephalitogenic T cells in vivo following TCV has yet to be studied. Here we used anti-MBP encephalitogenic T cells that were transduced to express GFP to study the effects of TCV on these cells. In naive rats or in control-vaccinated (Ova-GFP) rats injected i.v. with GFP-labeled effector cells, high numbers of effector T cells were found along with macrophages, CD8 T cells and Non-GFP CD4 cells in the spleens, parathymic lymph nodes (PTLN) and spinal cords. In contrast, the recipients that had been treated with TCV (anti-MBP T-cell lines) showed few if any GFP-labeled effector T cells throughout the disease (day 1-8) and their spinal cords were almost clear of macrophages, CD4 and CD8 cells. Splenocytes in the control groups secreted IFNgamma in response to MBP and showed high numbers of IFNgamma secreting CD4 and CD8 cells in their spinal cords at the disease peak. In the TCV-protected groups, splenocytes showed no reactivity to MBP but secreted IFNgamma in response to irradiated encephalitogenic T cells--an anti-idiotypic response. Thus, TCV leads to a marked decrease in the numbers of effector T cells in the CNS and lymphoid organs, to a marked reduction in the Th1 cytokine producing cells in the CNS, and to the appearance of T cells responsive to the anti-MBP effector T cells. PMID- 20580205 TI - Language, motor and speed of processing deficits in adolescents with subclinical psychotic symptoms. AB - OBJECTIVES: Neuropsychological impairment is a core feature of schizophrenia. Adolescents reporting subclinical psychotic symptoms are considered to be at greater risk of developing a psychotic illness later in life than adolescents who do not report such symptoms and, thus, may represent an at-risk group for further study. We wished to investigate neuropsychological functioning in early adolescence in relation to reports of psychotic symptoms. METHODS: Participants were recruited from local primary schools after a two-stage screening and parental consent process. In brief, 277 adolescents were screened and 37 attended for testing. Seventeen adolescents who were deemed to report 'definite' psychotic symptoms after clinical interview and 20 control adolescents underwent a clinical interview and a one-hour neuropsychological battery. RESULTS: Adolescents who report psychotic symptoms exhibited significant impairments in receptive language (as measured by the British Picture Vocabulary Scale), motor function (as measured by the Pegboard test) and executive function/speed of processing (as measured by the Trail-Making test). There were no significant differences between the groups on measures of attention, memory or expressive language, abstract reasoning or overall scholastic ability. CONCLUSIONS: Taken together with the results from birth cohort, genetic high risk and prodromal studies, these findings are consistent with a neural inefficiency/disconnectivity hypothesis in those at risk for psychosis. These results highlight the need to investigate developmental brain circuits subserving language and motor function and processing speed and how these change over time in at-risk adolescents. PMID- 20580206 TI - Possible effects of some antipsychotic drugs on C-reactive protein in a drug naive psychotic sample. AB - Antipsychotic effects on C-reactive protein (CRP) have received little attention. This randomized open-label study investigated the possible effects of antipsychotics on CRP levels after 3 and 12 months of treatment in a Spanish drug naive sample taking haloperidol (N=36 after 3 months), olanzapine (N=36 after 3 months) or risperidone (N=39 after 3 months). After 3 months and adjusting for differences in baseline CRP levels, baseline smoking and high baseline triglyceride levels, patients on haloperidol treatment had CRP levels that were 92.7% higher than those of patients on risperidone treatment (p=0.009). After 12 months, only smoking was associated with increased CRP levels. Future studies need to verify that different antipsychotics may have differential effects on CRP levels, particularly after 3 months of treatment. PMID- 20580207 TI - Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. AB - The mucolytic agent ambroxol has been reported to interfere with the formation of Pseudomonas aeruginosa-derived biofilms in addition to reducing alginate production by undefined mechanisms. Since quorum sensing is a key regulator of virulence and biofilm formation, we examined the effects of ambroxol on P. aeruginosa PAO1 wild-type bacterial clearance rates, adhesion profiles and biofilm formation compared with the quorum sensing-deficient, double-mutant strains DeltalasR DeltarhlR and DeltalasI DeltarhlI. Data presented in this report demonstrated that ambroxol treatment reduced survival rates of the double mutant strains compared with the wild-type strain in a dose-dependent manner even though the double-mutants had increased adhesion in the presence of ambroxol compared with the wild-type strain. The PAO1 wild-type strain produced a significantly thicker biofilm (21.64+/-0.57 microm) compared with the biofilms produced by the DeltalasR DeltarhlR (7.36+/-0.2 microm) and DeltalasI DeltarhlI (6.62+/-0.31 microm) isolates. Ambroxol treatment reduced biofilm thickness, increased areal porosity, and decreased the average diffusion distance and textual entropy of wild-type and double-mutant strains. However, compared with the double-mutant strains, the changes observed for the wild-type strain were more clearly defined. Finally, ambroxol exhibited significant antagonistic quorum sensing properties, suggesting that it could be adapted for use clinically in the treatment of cystic fibrosis and to reduce biofilm formation and in the colonisation of indwelling devices. PMID- 20580208 TI - Enhancement of the antibacterial properties of silver nanoparticles using beta cyclodextrin as a capping agent. AB - Silver nanoparticles (AgNPs) were synthesised by reducing silver salts using NaBH(4) followed by capping with varying concentrations of beta-cyclodextrin (beta-CD) and were physically characterised. Antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was determined by a microtitre well method. The AgNPs were spherical under transmission electron microscopy, whilst dynamic light scattering showed average diameters of capped particles to be smaller (4-7 nm) than their uncapped equivalents (17 nm). Capped particles demonstrated superior photostability when exposed to intense ultraviolet radiation for 4h as well as significantly (P<0.05) higher (up to 3.5 fold) antibacterial activity. The influence of beta-CD concentration was seen to delay bacterial growth, indicating that a Trojan horse mechanism may be occurring owing to bacterial carbohydrate affinity, thereby enhancing silver ion absorption. PMID- 20580209 TI - Seasonality and winter-type seasonal depression are associated with the rs731779 polymorphism of the serotonin-2A receptor gene. AB - Seasonal Affective Disorder (SAD), seasonality and increased sensitivity to the fluctuation of seasons in biological and psychological parameters can manifest to varying degrees across a normal population. The serotonin-2A (5-HT2A) receptor gene has long been suggested as a candidate for the genetic basis of this phenomenon. We hypothesized that functional sequence variation in this gene could contribute to seasonality and the development of winter- and/or summer-type seasonal depression. Seasonality was measured by the self-rating Global Seasonality Score (GSS) of the Seasonal Pattern Assessment Questionnaire, and SAD by the Seasonal Health Questionnaire (SHQ). We analysed associations between GSS or SAD scores and 5-HTR2A receptor gene polymorphisms rs731779, rs985934 and rs6311, in 609 individuals. People carrying the GG genotype of rs731779 were six times more likely to manifest winter or summer SAD compared to GT or TT genotypes (OR = 6.47), and the chance of having winter-type SAD was almost nine-fold (OR = 8.7) with the GG genotype. GG subjects of rs731779 also scored significantly higher on the GSS scale compared to carriers of the T allele. In the haplotype analysis subjects carrying the G allele of rs731779 scored higher on the GSS scale, while the presence of the T allele leads to lower scores. These results suggest that variations in the 5-HTR2A gene play a significant role in the development of seasonality and especially in winter-type SAD. The fact that the above polymorphism showed association not only with clinical SAD but also seasonality symptoms in a general population provides evidence for the spectrum nature of this connection. PMID- 20580210 TI - Effects of extraction procedures on metal binding properties of extracellular polymeric substances (EPS) from anaerobic granular sludges. AB - The effects of the extraction procedure of extracellular polymeric substances (EPS) on their proton/metal binding properties were studied. Nine extraction procedures (one control, four physical and four chemical procedures) were applied to four types of anaerobic granular sludges. The binding capacities between the EPS and lead or cadmium were investigated at pH 7 by a polarographic method. The composition of the EPS extracts varied according to the extraction technique and the origin of the sludge. This induced differences in the pK(a)s and the binding sites density of the EPS extracts. The carry-over of the extractant in the samples strongly affects the properties of the EPS from chemical extraction protocols. Lead and cadmium seem to be bound differently with the EPS, a higher binding capacity was observed for Pb(2+) than for Cd(2+). PMID- 20580211 TI - Heavy metals binding to biosorbents. Insights into Non-competitive models from a simple pH-dependent model. AB - The possible explanation for the applicability of NCAMs (Non-Competitive Adsorption Models, i.e. the models corresponding to the Langmuir model in which the maximum uptake value is pH-dependent) for biosorption systems is proposed. Both the metal ion speciation in the bulk solution and the formation of multidentate surface complexes are taken into account. This combined effect can be responsible for the specific behaviour of experimental metal sorption isotherms, measured at different pHs and described well by NCAMs. This concept finds its support in the numerical investigations performed by using the model biosorbent and Cu, Cd and Pb as heavy metals. Acid-base properties of typical biosorbent surfaces are also considered. PMID- 20580212 TI - Predicting malaria interactome classifications from time-course transcriptomic data along the intraerythrocytic developmental cycle. AB - OBJECTIVE: Even though a vaccine for malaria infections has been under intense study for many years, it has resisted several different lines of attack attempted by biologists. More than half of Plasmodium proteins still remain uncharacterized and therefore cannot be used in clinical trials. The task is further complicated by the metamorphic life-cycle of the parasite, which allows for rapid evolutionary changes and diversity among related strains, thus making precise targeting of the appropriate proteins for vaccination a technical challenge. We propose an automated method for predicting functions for the malaria parasite, which capitalizes on the importance of the intraerythrocytic developmental cycle data and expression changes during its five phases, as determined computationally by our segmentation algorithm. MATERIALS AND METHODS: Our method combines temporal gene expression profiles with protein-protein interaction data, sequence similarity scores, and metabolic pathway information to produce a set of predicted protein functions that can be used as targets for vaccine development. We use a Bayesian approach, which assigns a probability of having (or not having) a particular function to each protein, given the various sources of evidence. In our method, each data source is represented by either a functional linkage graph or a categorical feature vector. RESULTS AND CONCLUSIONS: The methods are tested on Plasmodium falciparum, the species responsible for the deadliest malaria infections. The algorithm was able to assign meaningful functions to 628 out of 1439 previously unannotated proteins, which are first-choice candidates for experimental vaccine research. We conclude that analyzing time-course gene expression profiles in separate phases leads to much higher prediction accuracy when compared with Pearson correlation coefficients computed across the time course as a whole. Additionally, we demonstrate that temporal expression profiles alone are able to improve the predictive power of the integrated data. PMID- 20580213 TI - Age dependent incorporation of 14C-DHA into rat brain and body tissues after dosing various 14C-DHA-esters. AB - INTRODUCTION: The omega-3 fatty acid docosahexaenoic acid (DHA) accounts for 10% of fatty acids in human brain and is critical for neuronal function and brain development. Mechanisms of transport, accumulation and conservation of DHA in the brain are unclear. The objective of the study was to quantify the age dependent DHA incorporation into the brain of 2-, 4- or 10-week-old rats after a bolus dose of different DHA-esters. METHODS: Rats were gavaged with (14)C-DHA-TAG, (14)C-DHA PL or (14)C-DHA-TAG+PL at 2 mg DHA/kg BW. After 24h the distribution of radioactivity in body and brain regions was determined using quantitative whole body autoradiography (QWBA). Radiolabeled compounds were extracted from the brains to determine the identity of the radiolabeled compounds. RESULTS: Accumulation of orally ingested (14)C-DHA in rat brain was less than 1% of the dose and decreased with age. Ester specific differences were seen only in 10-week old rats, where oral (14)C-DHA-PL delivered a 2-fold higher accretion of radioactivity in the brain. CONCLUSIONS: Less than 1% of a dietary achievable DHA dose reached the rat brain within 24h. Optimal efficacy of DHA-PL may occur in older age groups. PMID- 20580214 TI - Bacteria and MAMP-induced morphogenesis of the immune system. AB - To metazoans, bacteria are more than just potential pathogens. Many examples now document the role of bacterial symbionts in complementing the host for its full development and increasing its digestive and protective functions. Here, we discuss the role of Gram-negative bacteria in the development of intestinal lymphoid tissues and the impact of Segmented Filamentous Bacteria and Bacteroides on intestinal immunity and homeostasis. Furthermore, we discuss the potentially beneficial role of Helicobacter pylori on immunity of the stomach and beyond, even though this bacteria is primarily known for its pathogenicity. Altogether, these and other symbiotic bacteria may manipulate the host and the host immune system through the shedding of MAMPs that cross not only the epithelial barriers, but also permeate the circulation and impact every tissue and function of the host. PMID- 20580215 TI - Short-course fluoroquinolone therapy in exacerbations of chronic bronchitis and COPD. AB - Acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) are associated with significant healthcare costs and contribute to the progress of the disease. Although a number of factors may trigger these episodes, between 40% and 60% are bacterial in nature. Antimicrobial therapy can be effective in treating exacerbations, leading to improved peak expiratory flow rates, fewer hospitalizations, lower relapse rates, and greater clinical success. Evidence suggests that short-course antimicrobial therapy can be as effective as standard duration therapy (>7 days) in treating exacerbations. Randomized trials have shown that clinical and bacteriological success rates are comparable with both 5-day and standard antibiotic courses. Furthermore, 5-day fluoroquinolone therapy is associated with faster recovery, fewer relapses, prolonged duration between episodes, and less hospitalization when compared with standard therapy. Both moxifloxacin and gemifloxacin have received FDA-approval for 5-day therapy in AECB. PMID- 20580216 TI - Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. AB - BACKGROUND: It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). METHODS: On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim). RESULTS: FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. 0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR TIO was also related to larger increases in FEV(1) (p < 0.05). CONCLUSIONS: Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov]. PMID- 20580217 TI - Surface plasmon resonance study of PNA interactions with double-stranded DNA. AB - Peptide nucleic acid (PNA) is a well known DNA analogue bearing a N-(2 aminoethyl)glycine backbone (aegPNA). This molecule is able to not only form a duplex with single stranded (ss) nucleic acids but also higher-order (i.e., three and four-stranded) complexes with double-stranded (ds) DNA in a sequence specific manner. Here, the application of surface plasmon resonance (SPR) to study the binding of PNA to dsDNA is reported for the first time. SPR protocols were developed to verify the sequence rules and conditions for binding (pH and ionic strength) of homopyrimidine and homopurine aegPNAs to dsDNA, for which the solution phase behaviors are known, allowing a direct comparison. Then, using real-time SPR measurements, the hybridization efficiency, binding direction (antiparallel and parallel direction), sequence-dependent binding modes of the PNA to dsDNA (triplex formation and duplex invasion) and the binding kinetics associated with the binding mode were all ascertained. These SPR protocols were then further applied to study the dsDNA binding properties of a new conformationally rigid PNA bearing a D-prolyl-2-aminocyclopentanecarboxylic acid (ACPC) backbone (acpcPNA), which revealed that acpcPNA cannot form higher-order complexes with dsDNA through either triplex formation or duplex invasion. The SPR technique is thus shown to be a powerful technique for studying higher-order nucleic acid complexes. The binding behaviors of aegPNA obtained from the SPR analysis in the solid-liquid phase measurement correlate well with those in the literature derived from solution phase measurements. PMID- 20580218 TI - How apicomplexan parasites move in and out of cells. AB - Apicomplexan parasites utilize a unique form of 'gliding motility' to traverse across substrates, migrate through tissues, and invade into and finally egress from their vertebrate host cells. Parasite gliding relies on the treadmilling of surface adhesins linked to short actin filaments that are translocated rearward by stationary small myosin motors. New details reveal mechanistic insight into the coordinated release and processing of adhesins, the complexity of adhesin substrate interactions, the regulation of the actin-myosin motor complex, and the formation of a novel junction at the host-parasite interface. These activities are carefully orchestrated to provide an efficient process for motility that is essential for parasite survival. The parasite-specific nature of many of these steps reveals several essential points that may be targeted for intervention. PMID- 20580219 TI - Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: a meta-analysis of 22 studies. AB - The published data on the predictive and prognostic value of KRAS mutations in metastatic colorectal cancer (mCRC) treated with cetuximab seemed inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Systematic computerised searches of the PubMed, EMBase, BIOSIS, and SCOPUS were performed. A total of 22 studies were identified. Random-effects model or fix-effects model was used according to between-study heterogeneity. A total of 2188 mCRC patients were included in the final meta-analysis. The rate of KRAS mutations was 38% (829/2188). The overall response rate (ORR) of mutant KRAS patients was 14% (119/829), whereas the ORR of wild-type KRAS patients was 39% (529/1359). The overall pooled relative ratio (RR) for ORR was 0.24 (95% confidence intervals (CI): 0.16-0.38; P<0.01) when mutant KRAS patients were compared with wild-type KRAS patients. Median PFS was significantly shorter in mutant KRAS patients compared with that in wild-type KRAS patients (3.0 versus 5.8 months; HR=1.94; 95% CI: 1.62-2.33; P<0.01). Similarly, median OS was significantly shorter in mutant KRAS patients compared with that in wild-type KRAS patients (6.9 versus 13.5 months; HR=2.17; 95% CI: 1.72-2.74; P<0.01). The meta-analysis strongly suggests that KRAS mutations represent adverse predictive and prognostic biomarkers for tumour response and survival in mCRC patients treated with cetuximab. Patients with tumours that harbour mutant-type KRAS are more likely to have a worse response, PFS, and OS when treated with cetuximab. PMID- 20580220 TI - Tumour-mediated TRAIL-Receptor expression indicates effective apoptotic depletion of infiltrating CD8+ immune cells in clinical colorectal cancer. AB - Expression of apoptosis-related proteins on tumour cells has been shown in several experimental models to be an efficient mechanism for a counterattack against host anti-tumour immune responses in solid tumours. Here we provide a clinical evidence for such a tumour immune escape mechanism by demonstrating tumour to T cell-directed death receptor signalling (TRAIL/TRAIL-Receptor (TRAIL R)) in colorectal cancer (CRC). In a series of patients with CRC and completed 5 year follow up, we investigated apoptosis and expression levels of apoptosis related proteins. Gene and protein profiles in the tumours demonstrated intratumoural upregulated gene expression for Fas, Fas-L, TRAIL, TRAIL-R and TNF alpha (RT-qPCR). Levels of terminaldeoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labelling (TUNEL)-positive events were positively correlated with TRAIL-R1-expression on tumour infiltrating immune cells. Among the immune cells, preferentially CD8+ T cells were found to express TRAIL-R1 while serial immunostaining in the same patient tumours showed abundant apoptotic (TUNEL-positive) immune cells. In conclusion, our results in tumour samples from CRC patients suggest TRAIL-R1-mediated apoptotic depletion of infiltrating immune cells (CD8+) in response to TRAIL expression by the tumour itself. This supports the notion of an efficient escape from tumour immune response and thus evasion from the attack of activated CD8+ T cells. These findings may enhance our understanding of tumour progression in CRC and might be helpful for the development of TRAIL and its death receptor-based therapy. PMID- 20580221 TI - High-cell-density poly (3-hydroxybutyrate) production from sucrose using Burkholderia sacchari culture in airlift bioreactor. AB - Burkholderia sacchari IPT 189 poly (3-hydroxybutyrate) (P3HB) production in airlift bioreactor were investigated in batch and fed-batch culture using sucrose as carbon source. In batch experiments it was observed that during the growth phase B. sacchari IPT 189 might display exponential growth even at very low carbohydrate concentration, as long as NH(4)(+) concentration was above 190 mg l( 1). The onset of accumulation phase took place when NH(4)(+) concentration dropped below this value and continued as long as carbohydrate was in excess, even with dissolved oxygen concentration at 0.0% of air saturation. In the fed batch experiments, nitrogen limitation was used to induce P3HB biosynthesis in a two-phase process. In the first phase, an initial batch followed by a limited sucrose fed regime led to a growth with low-P3HB-content (less than 13%) and up to 60 g l(-1) of biomass concentration in c.a. 25 h. In the second phase, nitrogen concentration limitation induced P3HB accumulation up to 42%, raising the biomass concentration to c.a. 150 g l(-1). Calculated parameters for the experiments were P3HB productivity=1.7 gl(-1) h(-1) and P3HB yield factor from sucrose=0.22 g g(-1). PMID- 20580222 TI - Aggregate formation and polysaccharide content of Chlorella pyrenoidosa Chick (Chlorophyta) in response to simulated nutrient stress. AB - To determine how polysaccharide production influences microalgal aggregate size, we stimulated polysaccharide production using existing methods (previously applied to cyanobacteria and plants). Cultures were treated with glyoxylate (0, 0.25, 0.5, 1.25 mmol/L) to simulate nutrient stress and examined for 9 days (approaching stationary phase on day 9) to assess: growth rate, polysaccharide production (soluble, bound, and total), aggregate size, and the relation between polysaccharide and aggregate size. We found: 1.25 mmol/L glyoxylate inhibits growth, but 0.25 and 0.5 mmol/L do not, allowing comparisons of aggregate formation at lower concentrations; glyoxylate-induced polysaccharide production, which increased with increased glyoxylate concentration and time; an increase in relative abundance of cells bound together with increased glyoxylate addition; and increased glyoxylate-stimulated polysaccharide levels were directly correlated with aggregate size. This study indicates that glyoxylate may be used to examine microalgal ecophysiology and offers a method to predict the influence of nutrient stress on polysaccharide production. PMID- 20580223 TI - Pre-acclimation of a wastewater inoculum to cellulose in an aqueous-cathode MEC improves power generation in air-cathode MFCs. AB - Cellulose has been used in two-chamber microbial fuel cells (MFCs), but power densities were low. Higher power densities can be achieved in air-cathode MFCs using an inoculum from a two-chamber, aqueous-cathode microbial electrolysis cell (MEC). Air-cathode MFCs with this inoculum produced maximum power densities of 1070 mW m(-2) (cathode surface area) in single-chamber and 880 mW m(-2) in two chamber MFCs. Coulombic efficiencies ranged from 25% to 50%, and COD removals were 50-70% based on total cellulose removals of 60-80%. Decreasing the reactor volume from 26 to 14 mL (while maintaining constant electrode spacing) decreased power output by 66% (from 526 to 180 mW m(-2)) due to a reduction in total mass of cellulose added. These results demonstrate that air-cathode MFCs can produce high power densities with cellulose following proper acclimation of the inoculum, and that organic loading rates are important for maximizing power densities from particulate substrates. PMID- 20580225 TI - Evaluation of feeding glycerol on free-fatty acid production and fermentation kinetics of mixed ruminal microbes in vitro. AB - Ruminant-derived foods contain high proportions of saturated fats as a result of ruminal biohydrogenation that rapidly saturates and thus limits the availability of free unsaturated fatty acids for assimilation. The objective of this study was to evaluate the effects of glycerol on ruminal free-fatty acid (FFA) production rates and in vitro fermentation kinetics of alfalfa hay. In vitro incubations demonstrated 48% and 77% reductions in rates of FFA accumulation in incubations supplemented with 2% and 20% glycerol as compared to controls. In vitro incubations with alfalfa hay demonstrated that increasing levels of glycerol did not affect NDF digestibility of the hay. Additionally, increasing amounts of glycerol decreased the acetate to propionate ratio in the rumen. These results suggest that inhibiting bacterial fat degradation may promote ruminal passage of total lipid, thereby providing greater proportions of beneficial unsaturated fat for incorporation into beef products. PMID- 20580226 TI - Organosolv extraction of lignin from hydrolyzed almond shells and application of the delta-value theory. AB - The solubility of lignin from hydrolyzed almond (Prunus amygdalus) shells in different acetone, ethanol and dioxane-water mixtures and conditions (extraction time and temperature) was studied. The concept of the solubility parameter (delta value) was applied to explain the effect of organic solvent concentration on lignin solubility. The organic solvent-water mixture that led to the highest lignin extraction was composed of a 75% vol. of organic solvent for all the solvent series investigated (acetone, ethanol and dioxane). Moreover, the best lignin extraction conditions were a temperature of 210 degrees C and an extraction time of 40 min for the acetone and ethanol series, and 25 min for the dioxane series. The delta-value of the hydrolyzed almond shell lignin [14.60 (cal/cm(3))(1/2)] and that of the organic solvent-water mixtures was calculated. The experimental delignification capacity of the aqueous organic solvents clearly reflected the proximity of their delta-value to that of lignin. The hydrogen bonding capacity of the solvent-water mixtures was also taken into account. PMID- 20580224 TI - Biogas from grass silage - Measurements and modeling with ADM1. AB - Mono fermentation of grass silage without the addition of manure was performed over a period of 345days under mesophilic conditions (38 degrees C). A simulation study based on the IWA Anaerobic Digestion Model No. 1 (ADM1) was done in order to show its applicability to lignocellulosic biomass. Therefore, the influent was fractioned by established fodder analysis (Weender analysis and van Soest method). ADM1 was modified with a separate compound of inert decay products similar to the approach of Activated Sludge Model No. 1 (ASM1). Furthermore, a function, which described the influence of solids on the process of hydrolysis, has been integrated to reproduce reliable ammonium concentrations. The model was calibrated by using the modified Nash-Sutcliffe coefficient to evaluate simulation quality. It was possible to fit observed data by changing only hydrogen inhibition constants and the maximum acetate uptake rate. The extended ADM1 model showed good agreement with measurements and was suitable for modeling anaerobic digestion of grass silage. PMID- 20580227 TI - Bio-mitigation of CO(2), calcite formation and simultaneous biodiesel precursors production using Chlorella sp. AB - In this study, an attempt was made to use micro-algal system for the production of biodiesel precursors and simultaneous CO(2) mitigation. Chlorella sp. was found to have a higher growth rate as compared to the other algal species tested namely Chlamydomonas sp. and Synnecococcus sp. At different CO(2) concentrations (0.03%, 3%, 10% and 15%), the lipid productivity was 23.0, 20.0 and 27.3mg/L/d respectively. Calcite produced was characterized using FT-IR, SEM and XRD. The FAME in crude biofuel was analyzed by GC-FID that found to contain palmitic acid (C16:0), docosapentaenoic acid (C22:5) and docosahexaenoic acid (C22:6). The calorific value of Chlorella sp. was found to be 29kJ/g which is higher than values reported for fresh water microalgae making it a potential candidate to be used as an alternate fuel. PMID- 20580228 TI - Simultaneous production of lipases and biosurfactants by submerged and solid state bioprocesses. AB - Lipases and biosurfactants are compounds produced by microorganisms generally involved in the metabolization of oil substrates. However, the relationship between the production of lipases and biosurfactants has not been established yet. Therefore, this study aimed to evaluate the correlation between production of lipases and biosurfactants by submerged (SmgB) and solid-state bioprocess (SSB) using Aspergillus spp., which were isolated from a soil contaminated by diesel oil. SSB had the highest production of lipases, with lipolytic activities of 25.22U, while SmgB had 4.52U. The production of biosurfactants was not observed in the SSB. In the SmgB, correlation coefficients of 91% and 87% were obtained between lipolytic activity and oil in water and water in oil emulsifying activities, respectively. A correlation of 84% was obtained between lipolytic activity and reduction of surface tension in the culture medium. The surface tension decreased from 50 to 28mNm(-1) indicating that biosurfactants were produced in the culture medium. PMID- 20580229 TI - Conformational organizations of G-quadruplexes composed of d(G(4)T(n))(3)G(4). AB - Structural polymorphism is one of the important issues with regard to G quadruplexes because the structural diversity may significantly affect their biological functions in vivo and their physical property in nano-material. A series of oligonucleotides with four repeat guanines sequence [d(G(4)T(n))(3)G(4) (n=1-6)] were designed. In this study, the effects of loop length on the formation of structures of G-quadruplex were investigated through the result of CD (circular dichroism) and 20% non-denatured polyacrylamide gel electrophoresis. Our studies demonstrate that the length of loop in 100mM KCl solution could predict the conformation of G-quadruplex. PMID- 20580231 TI - 4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important. AB - Using computer aided modelling studies, a new extended P2/S2 interaction was identified. This extended region can accommodate a variety of functional groups, such as aryls and basic amines. It was discovered that the N3 nitrogen of the pyrimidine-2-carbonitrile is critical for its cathepsin cysteine protease inhibition. N1 nitrogen also contributes to the inhibitory activity, but to a very limited degree. An 'in situ double activation' mechanism was proposed to explain these results. PMID- 20580230 TI - Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways. AB - A thiazolidine-2,4-dione derivative, 3-(2-aminoethyl)-5-(3-phenyl-propylidene) thiazolidine-2,4-dione (2), was identified as a dual inhibitor of the Raf/MEK/ extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades. The discovered compound inhibited cell proliferation, induced early apoptosis, and arrested cells in G(0)/G(1) phase in human leukemia U937 cells. These results indicate its potential as a new lead compound to develop novel dual signaling pathway inhibitors and anticancer agents. PMID- 20580232 TI - Synthesis, antidepressant evaluation and QSAR studies of novel 2-(5H [1,2,4]triazino[5,6-b]indol-3-ylthio)-N-(substituted phenyl)acetamides. AB - In search for novel antidepressants, a series of 2-(5H-[1,2,4]triazino[5,6 b]indol-3-ylthio)-N-(substituted phenyl)acetamides was synthesized and screened for potential antidepressant activity by tail suspension test (TST) in mice. Number of synthesized compounds exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration (%DID). QSAR analysis was also undertaken which correlated three parameters FOSA, PISA, and glob with biological activity. PMID- 20580233 TI - T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones optimization, design and synthesis. AB - A series of spiro-azetidines and azetidinones has been evaluated as novel blockers of the T-type calcium channel (Ca(V)3.2) which is a new therapeutic target for the potential treatment of both inflammatory and neuropathic pain. Confirmation and optimization of the potency, selectivity and DMPK properties of leads will be described. PMID- 20580234 TI - Piperidinyl-nicotinamides as potent and selective somatostatin receptor subtype 5 antagonists. AB - Nicotinamides of benzyl-substituted 4-aminopiperidines and their seven-membered analogs of generic structure 2 and 2' have been discovered as potent and selective SST5 antagonists. The activity (K(i)) ranges from 2.4 to 436 nM. Most compounds exhibit decent physicochemical properties and follow a clear SAR pattern. Interestingly enough, the receptor is strongly enantiodiscriminating and binds in the amino-azepane-series only the (R)-enantiomer. PMID- 20580235 TI - Prevalent cardiac phenotype resulting in heart transplantation in a novel LMNA gene duplication. AB - Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy. PMID- 20580236 TI - Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors. AB - Following indications from pharmacophore-based virtual screening of natural product databases, morphinan and isoquinoline compounds were tested in vitro for acetylcholinesterase (AChE) inhibition. After the first screen, active and inactive compounds were used to build a ligand-based pharmacophore model in order to prioritize compounds for biological testing. Among the virtual hits tested, the enrichment of actives was significantly higher than in a random selection of test compounds. The most active compounds were biochemically tested for their activity on mu, delta, and kappa opioid receptors. PMID- 20580237 TI - Measurement of the (54)Mn half-life. AB - The half-life of (54)Mn was measured by following the decay of sources from a radiochemically pure solution using three different measuring systems: an ionisation chamber, a high-purity germanium (HPGe) detector and two 7.5 cm (diameter) * 7.5 cm (height) NaI(Tl) scintillation detectors in opposite position. The measurements were performed over a period of 3 years, i.e. about 3.5 half-lives of (54)Mn. The resulting half-life values and detailed uncertainty budgets are presented for the three measuring systems. The half-life obtained with the ionisation chamber, 312.32 (9) days, is consistent with but more precise than the ones obtained with the HPGe detector, 311.9 (5) days and the NaI(Tl) detectors, 311.9 (6) days, respectively. Our final half-life value of 312.32 (9) days is rather consistent with the currently recommended values of 312.29 (26) (IAEA, 2007) and 312.13 (3) days (Helmer and Schonfeld, 2004), even though the uncertainty of the latter may be underestimated. From a partially weighted mean (Pomme and Spasova, 2008) of selected experimental values published after 1970, a new best estimate of T(1/2)((54)Mn)=312.20 (8) days was calculated. PMID- 20580238 TI - Click chemistry for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin. AB - (99m)Tc-HYNIC labeled Lys(3)-bombesin has shown specific binding to gastrin releasing peptide receptors (GRP-r) over-expressed in cancer cells. Click chemistry offers an innovative functionalization strategy for biomolecules such as bombesin. The aim of this research was to apply a click chemistry approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin and to compare the in vitro MCF7 breast cancer cell uptake and biodistribution profile in mice with that of (99m)Tc-EDDA/HYNIC-Lys(3)-bombesin. The results suggest a higher lipophilicity for (99m)Tc(CO)(3)-triazole-Lys(3)-bombesin which explains its higher in vivo hepatobiliary elimination. Pancreas-to-blood ratio for (99m)Tc(CO)(3)-triazole Lys(3)-bombesin was 4.46 at 3 h and both bombesin radiopharmaceuticals showed specific recognition for GRP receptors in MCF7 cancer cells. Click chemistry is a reliable approach for [(99m)Tc(CO)(3)] labeling of Lys(3)-bombesin. PMID- 20580239 TI - Antioxidative responses of Ocimum basilicum to sodium chloride or sodium sulphate salinization. AB - Soils and ground water in nature are dominated by chloride and sulphate salts. There have been several studies concerning NaCl salinity, however, little is known about the Na(2)SO(4) one. The effects on antioxidative activities of chloride or sodium sulphate in terms of the same Na(+) equivalents (25 mM Na(2)SO(4) and 50 mM NaCl) were studied on 30 day-old plants of Ocimum basilicum L., variety Genovese subjected to 15 and 30 days of treatment. Growth, thiobarbituric acid reactive substances (TBARS), relative ion leakage ratio (RLR), hydrogen peroxide (H(2)O(2)), ascorbate and glutathione contents as well as the activities of ascorbate peroxidase (APX, EC 1.11.1.11); glutathione reductase (GR, EC 1.6.4.2) and peroxidases (POD, EC 1.11.1.7) were determined. In leaves, growth was more depressed by 25 mM Na(2)SO(4) than 50 mM NaCl. The higher sensitivity of basil to Na(2)SO(4) was associated with an enhanced accumulation of H(2)O(2), an inhibition of APX, GR and POD activities (with the exception of POD under the 30-day-treatment) and a lower regeneration of reduced ascorbate (AsA) and reduced glutathione (GSH). However, the changes in the antioxidant metabolism were enough to limit oxidative damage, explaining the fact that RLR and TBARS levels were unchanged under both Na(2)SO(4) and NaCl treatment. Moreover, for both salts the 30-day-treatment reduced H(2)O(2) accumulation, unchanged RLR and TBARS levels, and enhanced the levels of antioxidants and antioxidative enzymes, thus achieving an adaptation mechanism against reactive oxygen species. PMID- 20580240 TI - Face perception in patients with unilateral cleft lip and palate and patients with severe Class III malocclusion compared to controls. AB - Although there is principal agreement that increased facial asymmetry is associated with decreased facial attractiveness, there are no studies analysing face perception in patients with a unilateral cleft lip and palate (CLP) (uCLP) compared to orthognathic Class III patients. To this end, three-dimensional (3D) data on the faces of 30 adults with a complete uCLP, 20 orthognathic patients with a severe skeletal Class III, and 20 adults with a skeletal Class I as a control group were generated. The 3D asymmetry of the facial soft-tissue was analysed. These data were compared with subjective ratings for attractiveness carried out by 100 laypersons. Compared to the controls, uCLP patients and orthognathic patients had a significantly higher facial asymmetry. No difference was found between uCLP patients and orthognathic patients. The attractiveness ratings showed that uCLP patients and orthognathic patients were rated less attractive compared to the controls. However, although there were no differences in the facial asymmetry between uCLP patients and orthognathic patients, the uCLP patients were rated significantly less attractive. This leads to the conclusion that not only the extent of asymmetry has an influence on attractiveness but also the location of asymmetry. For clinical use, these findings underline the importance of accurate as possible surgical reconstruction of the nasal morphology in uCLP patients. PMID- 20580241 TI - Fibro-osseous dysplasia localized to the zygomatic arch: case report. AB - Fibrous dysplasia is an osseous growth disorder, producing immature bone characterized by the replacement of normal bone with fibro-osseous connective tissue. The therapy is surgical, but the diagnosis of fibrous dysplasia of the craniofacial bones is not in itself an indication for treatment. The authors present a rare case of a zygomatic arch localization of fibrous dysplasia causing considerable facial asymmetry and social impairment. The clinical and radiological features are presented, the surgical procedure and indications are then described and the histopathological findings are discussed. PMID- 20580242 TI - New minimally invasive technique for correction of pectus carinatum. AB - We describe a new video-assisted operative technique for correction of pectus carinatum (PC) using a modified Nuss procedure. A new design of the steel bar was developed, so that it could be introduced and placed in a suitable position through very small skin incisions. Substantial modifications were introduced in the bar length and shape aimed at facilitating insertion and subsequent removal when required. All the surgical manoeuvres took place under direct vision using a 30 degrees thoracoscope. Single unilateral fixation of the bar in a subpectoral pocket provided satisfactory stabilisation without the need for lateral stabilisers. Adequate correction of the deformity was achieved with minor postoperative scars. Our results support the view that minimally invasive surgical repair should be preferred over open surgery for correction of pectus carinatum in young adults and children. PMID- 20580243 TI - Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma. AB - OBJECTIVE: Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient's prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients. MATERIAL AND METHODS: The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. The median (range) patients' age was 62 (28-83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKT and scored by two independent pathologists. Intensity of ILK and pAKT expression has been correlated with disease-related survival. RESULTS: In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease related survival according to ILK or pAKT expression, no statistically significant difference could be found between ILK and pAKT expressing or non expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression had a longer 5-year disease-related survival (p < 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p = 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p = 0.005). CONCLUSION: The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKT expression has a measurable influence on the patient's prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKT expression in MPM, prospective trials are needed. PMID- 20580244 TI - Donor predicted post-operative forced expiratory volume in one second predicts recipients' best forced expiratory volume in one second following size-reduced lung transplantation. AB - OBJECTIVE: The limited number of available grafts is one of the major obstacles of lung transplantation. Size-reduced lung transplantation allows the use of oversized grafts for small recipients. Optimal lung size matching is vital to achieve best functional outcome and avoid potential problems when using oversized grafts. We hypothesise that donor-predicted postoperative forced expiratory volume in 1s (ppoFEV1) correlates with the recipient best FEV1 after size-reduced lung transplant, being useful for the estimation of function outcome. METHODS: All patients undergoing size-reduced or standard bilateral lung transplantation were included (1992-2007). Donor ppoFEV1 was calculated and corrected with respect to size reduction and correlated with recipient measured best FEV1 post transplant. In addition, pre- and postoperative clinical data including surgical complications and outcome of all size-reduced lung transplant recipients were compared with standard lung transplant recipients. RESULTS: A total of 61 size reduced lung transplant recipients (lobar transplants, n=20; anatomic or non anatomic resection, n=41) were included and compared to 145 standard transplants. The mean donor-recipient height difference was statistically significant between the two groups (p=0.0001). The mean donor ppoFEV1 was comparable with recipient best FEV1 (2.7+/-0.6 vs 2.6+/-0.7 l). There was a statistically significant correlation between donor ppoFEV1 and recipient best FEV1 (p=0.01, r=0.688). The 30-day mortality rate and 3-month, 1- and 5-year survival rates were comparable between the two groups. CONCLUSIONS: In size-reduced lung transplantation, postoperative recipient best FEV1 could be predicted from donor-calculated and corrected FEV1 with respect to its size reduction. Compared to standard lung transplantation, equivalent morbidity, mortality and functional results could be obtained after size-reduced lung transplantation. PMID- 20580245 TI - Long-term survival of 42 patients with resected N2 non-small-cell lung cancer: the impact of 2-(18)F-fluoro-2-deoxy-D-glucose positron emission tomogram mediastinal staging. AB - OBJECTIVE: Prognostic information known preoperatively allows stratification of patients to surgery; induction therapy and surgery; or definitive chemoradiotherapy and may prevent a futile thoracotomy. Attention has focussed on the standard uptake value (SUV) of the primary tumour but less has been described regarding the 18F-fluoro-2-deoxy-D-glucose (18F-FDG) avidity of mediastinal nodes. We aimed, in a group of surgically resected cN0-1 but pN2 tumours, to compare the survival of patients with and without 18F-FDG avid mediastinal nodes. METHODS: Retrospective review of a surgical database identified cN0-1 non-small cell lung cancer (NSCLC) patients with pN2 disease after resection. Survival of non-FDG avid N2 versus FDG avid N2 groups was compared after stratification according to variables found on univariate analysis to affect survival. RESULTS: From January 1993 to December 2006, 42 patients were identified; 27 (64%) had non FDG avid N2 disease. Five-year and median survival were better in the non-FDG avid N2 disease group, 25% versus 0% and 30 (16-44) versus 13 (10-16) months, respectively (p=0.02). After 1998, the difference in survival was 41% versus 0% and 35 (14-56) versus 12 (16-18) months, respectively (p=0.02). CONCLUSIONS: After resection, patients with non-FDG avid N2 disease have better survival than patients with FDG avid N2 disease. Exploratory thoracotomy alone (after frozen section analysis) cannot be advocated in patients with non-FDG avid N2 disease as survival after resection appears at least equivalent to alternate therapeutic approaches in this group. This assertion may be tempered if right pneumonectomy is required or R0 resection is unachievable. Mediastinal nodal avidity may improve stratification in future studies of long-term survival in NSCLC. PMID- 20580246 TI - A simple, new technique for identifying the cut line in the bronchus in bronchoplasty using a butterfly needle. AB - The standard method of bronchoscopic guidance used to identify a bronchial or tracheal tumour during surgery has some disadvantages: (1) it is impossible to identify the incision site in a distal bronchus; (2) bronchoscopy must be performed by a skilled physician; and (3) time and effort are wasted during the operation. We report a new and simple technique to locate endobronchial tumours. Our technique uses a butterfly needle connected to a syringe kept half-full of normal saline solution via an extension tube. The bronchus is punctured using the needle, keeping the syringe under negative pressure. We found that a tumour could be detected through simple observation of the saline solution within the syringe upon bronchial puncture, whereby the tumour is positively detected through the absence of bubble production and ruled out through the production of bubbles. This technique will locate a bronchial or tracheal tumour without bronchoscopy. In addition, it saves time, which benefits the patient. PMID- 20580247 TI - Outcomes and re-interventions after one-stage repair of transposition of great arteries and aortic arch obstruction. AB - OBJECTIVES: One-stage repair of transposition of great arteries (TGA) and aortic arch obstruction (AAO) is currently advocated, but carries formidable surgical challenges. This report presents our experience and re-interventions for residual lesions over the last 10 years. METHODS: Twenty-two patients (19.5 +/- 42.4 days; range 2-206; median 10 days, 3.5 +/- 0.6 kg) diagnosed with TGA (nine patients) or double outlet right ventricle (DORV) (13 patients) and AAO underwent one-stage repair. Of the nine TGA patients (two with intact ventricular septum), AAO were: two patients hypoplastic arch, one patient discrete coarctation, four patients hypoplastic arch with coarctation and two patients interrupted aortic arch. The 13 DORV patients were all of Taussig-Bing type and one showed multiple ventricular septal defects (VSDs). The degree of AAO ranged from hypoplastic arch in five patients, coarctation two patients, combined four patients and interrupted aortic arch (IAA) two patients. Arterial switch with Lecomte +/- VSD repair was performed during cooling, and aortic arch repair was performed under deep hypothermic circulatory arrest (DHCA) (35 +/- 14 min at 16.9 +/- 0.7 degrees C). Our preference was to use homograft patch-plasty for arch and direct end-to-side anastomosis for coarctation repair. Aortic-cross-clamp time was 124 +/- 24 min and cardiopulmonary bypass (CPB) time 215 +/- 84 min. RESULTS: Early survival was 19/22 (86%) up to 30 days without mortality in the second half of our series. Three patients required extracorporeal membrane oxygenation (ECMO) support and renal support was needed in three and preferred permanent pace maker (PPM) implantation in two. Length of stay was 21.9 +/- 22.1 days. There was one late death and overall survival was 18/22 (82%) for the follow-up period of 4.8 years (0.2-9.8 years). Eight patients (44%) required re-intervention for re coarctation. Four patients required right ventricular outflow tract (RVOT)/pulmonary artery re-interventions. At follow-up, there was no requirement for aortic valve replacement, residual VSD closure and no evidence of ventricular dysfunction. CONCLUSIONS: One-stage repair of TGA/DORV and AAO can be performed safely with a good survival rate. Three important lessons that we have learnt are as follows: (1) the subpulmonary VSD may have a perimembraneous component, (2) late re-coarctation is not infrequent and (3) late residual right-sided cardiac lesions remain an issue in complex TGA repair. PMID- 20580248 TI - Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability. AB - Growth factors control the proliferation and differentiation of osteoprogenitor cells. This study explores the effects of modulating growth factors (VEGF, IGF-1, FGF-2 and BMP-2) on osteogenesis of mesenchymal stem cells (MSCs) in vitro. Constant and profiled delivery protocols, in accordance with protein expression in vitro, were applied to deliver or neutralize growth factors. Cell number, alkaline phosphatase (ALP-2) and osteocalcin (OC) expression, and mineralization were measured as outcome variables. Profiled addition of VEGF increased MSC proliferation. Constant and profiled application of FGF-2 and neutralization of IGF-1 and BMP-2 decreased ALP-2 levels. Profiled addition of BMP-2 vastly increased OC release from MSCs, but constant addition of IGF-1, constant and profiled neutralization of IGF-1 and FGF-2 reduced OC levels. Constant addition of IGF-1 and FGF-2, as well as profiled loading of FGF-2 decreased mineralization of MSCs. This study indicated that endogenous IGF-1 and FGF-2 are essential to osteogenesis; excess IGF-1 and FGF-2 were inhibitory to bone formation. Selective, temporally specific addition of growth factors, such as BMP-2 and VEGF appears to be an important strategy to enhance osteogenesis. PMID- 20580249 TI - The modulative effect of Cyperi Rhizoma on Th1/Th2 lineage development. AB - To evaluate the direct effects of Cyperi Rhizoma (CR), a plant water extract, on Th1/Th2 lineage development in vitro, this study was conducted. Sorted CD4(+) T cells obtained from the splenocytes of BALB/c mice were activated with anti CD3/anti-CD28 and then cultured in medium that contained CR medium under Th1 inducing or Th2 inducing conditions. Subsequently, IFN-gamma or IL-4 secreting cells were quantitated using flow cytometry analysis. In addition, IFN-gamma and IL-4 protein secretions were detected by ELISA analysis, after which, IFN-gamma and T-bet transcripts, key players in the Th1 immune function, and also, IL-4 and GATA-3, which are primary components in the Th2 immune mechanism, were quantitated by real-time RT-PCR. CR had no mitogenic effects on un-stimulated CD4(+) T cells, however, it increased the CD4(+) T cell population. Th1/Th2 polarization experiments revealed that CR enhanced IFN-gamma secretion in Th1 cells, but reduced the IL-4 in Th2 cells, and this occurred in a dose-dependent manner and showed significances. In addition, under Th1/Th2 skewed conditions, the transcription levels of IFN-gamma and T-bet were considerably increased, while the expressions of IL-4 and GATA-3 were relatively decreased with CR treatment. These findings suggest that CR enhances Th1 lineage development by increasing Th1 specific cytokine expression and secretion and reduces Th2 lineage development by repressing Th2 specific cytokine productions. Therefore, CR extract may be useful for preventing the onset of allergies or improving allergic symptoms. PMID- 20580250 TI - Relationship between body mass index and mortality in adults on maintenance hemodialysis: a systematic review. AB - OBJECTIVE: The primary objective of this systematic review was to determine the relationship between body mass index (BMI) and all-cause and cardiovascular mortality. DESIGN: Systematic review of primarily observational studies. PATIENTS: Adult patients from all gender, race, or ethnic groups on maintenance hemodialysis. METHODS: Medline, Science Citation Index, Academic Search Premier, Cochrane Library, and Embase electronic databases covering the period 1966 to December 2008 were searched with the help of a qualified librarian. Reference lists of included papers and collections also were searched. Each study was reviewed by 2 independent reviewers who also performed the data extraction from full papers. Differences between reviewers were resolved by consensus or by a third reviewer in the case of disagreements. The quality of studies selected for inclusion in the systematic review was also assessed by 2 independent reviewers. MAIN OUTCOMES: BMI and mortality. RESULTS: Eighteen studies (60%) reported a significant inverse relationship between all-cause mortality and BMI. This inverse relationship was more prevalent in older patients, larger retrospective studies, and studies that did not adjust for inflammation. On the other hand, 57% of the 7 studies reporting on cardiovascular mortality found no significant relationship with BMI. CONCLUSIONS: This systematic review shows evidence of an inverse relationship between BMI and all-cause mortality in adult patients on maintenance HD, especially in older patients, but the relationship with cardiovascular mortality is less clear. PMID- 20580252 TI - Imputation methods for handling missing dietary supplement dosage data. PMID- 20580251 TI - The effect of resistance exercise to augment long-term benefits of intradialytic oral nutritional supplementation in chronic hemodialysis patients. AB - BACKGROUND: Resistance exercise combined with intradialytic oral nutrition (IDON) supplementation improves net protein balance in the acute setting in chronic hemodialysis patients. We hypothesized that combination of long-term resistance exercise and IDON would improve markers of muscle mass and strength further compared with IDON alone. METHODS: Thirty-two participants (21 male; mean age, 43 +/- 13 years) on chronic hemodialysis were randomly assigned to IDON plus resistance exercise (NS + EX), or IDON (NS) alone for 6 months. IDON consisted of a lactose-free formula consisting of protein, carbohydrate, and fat. Three sets of 12 repetitions of leg-press were completed before each dialysis session in the NS + EX arm. Primary outcome measurement was lean body mass. Muscle strength and other nutritional parameters were measured as secondary outcomes. RESULTS: Of 32 participants, 22 completed the 6-month intervention. There were no statistically significant differences between the study interventions with respect to changes in lean body mass and body weight, when comparing NS + EX to NS. There were also no statistically significant differences in any of the secondary outcomes measured in the study. Body weight (80.3 +/- 16.6 kg, 81.1 +/- 17.5 kg, and 80.9 +/- 18.2 kg at baseline, month 3, and month 6, respectively; P = .02) and 1 repetition maximum (468 +/- 148 lb, 535 +/- 144 lb, and 552 +/- 142 lb, respectively; P = .001) increased statistically significantly during the study for all patients combined. CONCLUSION: This study did not show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone. When both treatments groups were combined, body weight and muscle strength improved during the study. PMID- 20580254 TI - Risk factors for small cortical infarction on diffusion-weighted magnetic resonance imaging in patients with acute ischemic stroke. AB - Diffusion-weighted magnetic resonance imaging (MRI) is sensitive for detecting acute ischemic lesions. The present study evaluated risk factors associated with small cortical infarction (SCI) on diffusion-weighted MRI. We analyzed 123 patients with acute ischemic stroke retrospectively. We defined an SCI as a cortical lesions < 1.5 cm in diameter detected by diffusion-weighted MRI. Risk factors and comorbidities included hypertension, hypercholesterolemia, diabetes mellitus, cigarette smoking, potential cardiac sources of embolism, carotid disease, and coagulopathy. Carotid disease was defined as > 50% stenosis or occlusion in the internal carotid artery, detected by carotid ultrasonography. In addition, we analyzed plasma levels of coagulation and fibrinolysis markers. We also compared carotid disease, potential cardiac sources, and coagulopathy among localization of SCI. SCI was identified in 22.8% of patients with acute ischemic stroke. Carotid disease (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 1.7-11.42; P = .002) and coagulopathy (OR = 6.8; 95% CI = 1.33-35.17; P = .02) were found to be independent risk factors for SCI. SCI with carotid disease was not associated with bilateral and multiple territorial lesions, whereas SCI with coagulopathy was associated with bilateral lesions. No borderzone lesions were found in SCI patients with cardiac sources. Our findings suggest that carotid disease and coagulopathy are independent risk factors for SCI. Localization of SCI varies depending on the underlying diseases. PMID- 20580253 TI - Segment-specific association between plasma homocysteine level and carotid artery intima-media thickness in the Framingham Offspring Study. AB - Elevated plasma total homocysteine (tHcy) level is an established risk factor for cardiovascular disease. The relationship between tHcy and carotid artery intima media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT had not been systematically studied, however. Because the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action. We examined the cross-sectional segment-specific relationships of tHcy to ICA/bulb-IMT and CCA-IMT in 2499 participants from the Framingham Offspring Study who were free of cardiovascular disease. In multivariate linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared with the other quartile categories, in both the age- and sex-adjusted and the multivariate-adjusted models (P for trend <.0001 and <.01, respectively). We observed a significant age-by-tHcy interaction for ICA/bulb-IMT (P=.03) and thus stratified the analyses by median age (58 years). A significant positive trend between tHcy and ICA/bulb-IMT was seen in individuals age >=58 years (P for trend <.01), but not in younger individuals (P for trend=.24) in multivariate-adjusted models. For CCA-IMT, no significant trends were observed in any of the analyses. The segment-specific association between elevated tHcy level and ICA/bulb-IMT suggests an association between tHcy and plaque formation. PMID- 20580255 TI - Effect of edaravone on the estimated glomerular filtration rate in patients with acute ischemic stroke and chronic kidney disease. AB - The oxygen free radical scavenger edaravone is used in patients with acute ischemic stroke in Japan, but adverse reactions, especially decreased renal function, have raised concerns. To examine whether a patient's estimated glomerular filtration rate (eGFR) at admission can predict renal function deterioration after edaravone treatment, we retrospectively evaluated the effect of edaravone on eGFR in Japanese patients with acute ischemic stroke and chronic kidney disease (CKD). The baseline eGFR in the edaravone-treated group (73.5+/ 20.3 mL/min/1.73 m(2); n=408) at admission was significantly (P < .05) higher than that in the non-edaravone-treated group (51.9+/-25.2 mL/min/1.73 m(2); n=41). The change in eGFR after treatment was categorized into 3 grades: nonexacerbation (<=10%), 10%-30% exacerbation, and >30% exacerbation. There was no significant difference in exacerbation grade between the edaravone-treated and non-edaravone-treated groups (chi(2) =3.134; P=.21). We next subdivided the edaravone-treated group according to eGFR at admission as either CKD (eGFR <60 mL/min/1.73 m(2); n=111) and non-CKD (n=297). No significant decrease in eGFR was seen even in the edaravone-treated CKD group (most of whom were in stage 3 CKD). Decreased eGFR in stroke patients was found to be associated with stroke subtype (cardiogenic stroke), but not with infection. The present study demonstrates that eGFR at admission is not a good predictor of renal deterioration in edavarone treated acute ischemic stroke patients, including those with stage 3 CKD. PMID- 20580256 TI - Causes of ischemic stroke in young adults in Thailand: a pilot study. AB - There is scarce information about ischemic stroke in young adults in Thailand. The purpose of this study was to explore the causes of ischemic stroke in Thai adults age 16-50 years. All ischemic strokes treated in persons in this age range between August 2006 and December 2008 were prospectively included. Stroke subtypes were classified according to Trial of ORG 10172 in Acute Stroke Treatment criteria as large-artery atherosclerosis (LAA), cardioembolism (CE), small-artery occlusion (SAO), stroke of other determined cause (OC), or stroke of undetermined cause (UND). The study group comprised 99 patients, with a mean age of 40 years and a mean National Institutes of Health Stroke Scale score of 8. In patients age <41 years, UND (32%; P = .0652) and OC (30%; P = .0167) were the most common stroke subtypes. In patients age 41-50 years, SAO (29%; P = .0947) and UND (21%) were the most common subtypes. Antiphospholipid syndrome (6%) and neurosyphilis (4%) were the leading causes of the OC subtype. Hyperlipidemia, smoking, and hypertension were common risk factors. Although the distribution of stroke subtypes was comparable with that found in previous studies from other countries, the identified causes were different. PMID- 20580257 TI - One-month to 10-year survival in the Copenhagen stroke study: interactions between stroke severity and other prognostic indicators. AB - We studied the association of stroke severity with survival from 1 month to 10 years after stroke and explored how stroke severity interacts with other prognostic indicators with time. The study is based on 999 stroke patients from the community-based Copenhagen Stroke Study (mean age, 74.3+/-11.0 years; 56% women; mean Scandinavian Stroke Scale [SSS], 38.0+/-17.4). Evaluation included stroke severity (based on the SSS), computed tomography scan, and a cardiovascular risk profile. Using logistic regression models, we examined the relevance of the SSS on mortality at 1 month and 1, 5, and 10 years. We analyzed the proportion of the variation explained by the models and bias of risk factors estimates with and without the SSS in the model. Mortality rate was 16.6% at 1 month, 31.5% at 1 year, 60.2% at 5 years, and 81.3% at 10 years. In models including the SSS, 22.4%, 20.9%, 32.8%, and 39.5% of the variance was explained for the endpoints of 1 month, 1 year, 5 years, and 10 years, respectively. When SSS was left out of the model, the corresponding values were 6.9%, 13.3%, 29.0%, and 35.1%. Factors significantly associated with survival were SSS at 1 month; SSS, age, diabetes, and stroke type at 1 year; SSS, age, sex, previous stroke, other complicating diseases, diabetes, smoking, and atrial fibrillation at 5 years; and SSS, age, sex, other complicating diseases, and diabetes at 10 years. Our data suggest that stroke severity is significantly associated with short-term and long-term survival. It is the all-important predictor of short-term survival, whereas it is of less importance in predicting long-term survival. PMID- 20580258 TI - Mismatch: when the imaging studies conflict with the neurologic exam. AB - As neurologists, we increasingly rely on imaging studies to help us diagnose acute stroke. This unusual case is a reminder that even sophisticated imaging techniques can have false negatives and emphasizes the importance of the clinical exam. PMID- 20580259 TI - Clinical correlating factors and cognitive function in community-dwelling healthy subjects with cerebral microbleeds. AB - We performed brain gradient-echo T2(*)-weighted magnetic resonance imaging (GE MRI) in community-dwelling healthy people to investigate the clinical correlates (i.e., possible risk factors) and cognitive function in subjects with cerebral microbleeds (MBs). We examined 368 healthy subjects age 39 years or older living in a Japanese rural community, performing baseline and clinical assessments and brain MRI (T2(*)-weighted, T1-weighted, T2-weighted, and FLAIR). We assessed global cognitive function in subjects age 60 years or older using the Mini-Mental State Examination (MMSE). An MMSE score >1.5 standard deviations (SD) below the mean score for a particular age group was considered subnormal. MBs were present in 14 of 368 subjects overall (3.8%; 11 males and 3 females) and in 14 of 225 subjects age>=60 years (6.2%). In a logistic regression analysis, older age (odds ratio [OR]=2.649/10 years; 95% confidence interval [CI]=1.465-4.788) and male sex (OR=6.876; 95% CI=1.801-26.248) were significantly related to the presence of MBs. The presence of silent brain infarction and white matter lesions was correlated with MBs, suggesting that MBs were the consequence of small-vessel diseases. There was a significant association between the presence of MBs and subnormal cognition defined by MMSE (OR=5.226; 95% CI=1.463-18.662). Our data suggest that in healthy community-dwelling subjects, MBs may be a consequence of small-vessel disease, which is correlated with aging, male sex, and subnormal cognition. PMID- 20580260 TI - Impact of previous cardiovascular disease on the outcome of lung transplantation. AB - BACKGROUND: The impact of previous cardiovascular disease on the outcome of lung transplantation may be important but remains unstudied. METHODS: Cardiovascular risk factors, echocardiography, right heart catheterization, isotopic ventriculography and vascular ultrasonography data were obtained from 258 adults who underwent lung transplantation at our center between 1988 and 2007. The effect of these parameters on survival and cardiovascular disease after transplantation was determined using the Cox model. RESULTS: By multivariate analysis, diabetes (hazard ratio [HR]: 2.4), atrial fibrillation (HR: 3.51), elevated systolic pulmonary artery pressure (HR: 1.23 per 10 mm Hg) and low cardiac index (HR: 1.47 per-liters/min/m(2)) before transplantation were associated with a higher risk of death after transplantation. Heart failure (2.08 cases per 100 patient-years) and atherothrombosis (2.5 cases per 100 patient years) were frequent after lung transplantation. A history of atherothrombosis (HR: 12.98) and diabetes (HR: 5.8) before transplantation were associated with a higher risk of atherothrombosis after transplantation. Major cardiovascular events led to death in 11 patients. Diabetes (HR: 62.5) and a low cardiac index (HR: 6.8 per-liters/min/m(2)) were associated with a higher risk of death from cardiovascular causes. CONCLUSIONS: Diabetes and a history of atrial fibrillation before lung transplantation were associated with excess mortality after transplantation. Diabetes was also associated with a major increase in the risk of atherothrombosis and death from cardiovascular causes. Lung transplant recipients may be considered at high risk for cardiovascular disease. PMID- 20580261 TI - Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data. AB - BACKGROUND: Donor and recipient risk factors for rejection and infection have been well characterized. The contribution of demographic factors, especially age at the time of transplantation to morbidity and mortality due to rejection and infection, is much less well understood. METHODS: Using parametric hazard analysis and multivariate risk-factor equations for infection and rejection events, we quantitatively determined the relationship of fundamental demographic variables (age, race and gender) to infection and rejection. These analyses were conducted with respect to date of transplant and age at the time of transplantation. The patient group consisted of all primary heart transplants performed at the University of Alabama at Birmingham during the years 1990 to 2007 (n = 526). RESULTS: Risk factors for rejection within 12 months post transplantation were date of transplant (p < 0.0001) and age at the time of transplantation (young adults 10 to 30 years of age, p < 0.0001). Risk factors for infection were date of transplant (p < 0.0001) and age at the time of transplantation (young children and older adults, p < 0.0001). There were three immunosuppressive eras in 1990 to 2007. Notably, although the proportion of patients experiencing rejection and infection events decreased during each successive immunosuppressive era, the relative relationship of infection to rejection, as well as age at the time of transplantation, remained similar into the most recent era. The maximal frequency of rejection events and rejection death occurred among patients transplanted at ages 10 to 30 years. Conversely, the frequency of infection events was minimal within the same group. In the oldest and youngest patients receiving transplants, infection was the predominant cause of death and rates of rejection events decreased. CONCLUSIONS: These data show that evolving immunosuppressive strategies have successfully reduced rejection and infection frequencies, and those patients transplanted at 30 to 60 years of age have the lowest frequency of rejection/infection events. However, individuals transplanted at younger or older ages, especially non-white recipients in the 10- to 30-year age group, experience significantly more infection or rejection. Therefore, programs should increase the level of surveillance in these patients and consider modification of immunosuppressive regimens in order to lower the frequency of infection and rejection events. PMID- 20580262 TI - Third sequential bilateral lung transplant. PMID- 20580263 TI - Cardiomyocyte-targeted HIF-1alpha gene therapy inhibits cardiomyocyte apoptosis and cardiac allograft vasculopathy in the rat. AB - BACKGROUND: Hypoxia-inducible factor-1 (HIF-1), a key transcription factor in hypoxia, affects a wide range of adaptive cell functions. We examined the kinetics of endogenous HIF-1alpha during acute and chronic rejection, and the effect of exogenous HIF-1alpha in chronically rejecting rat cardiac allografts. METHODS: Heterotopic cardiac transplantations were performed between major MHC mismatched Dark Agouti and Wistar-Furth rats. Cyclosporine A (CsA) was used to prevent acute rejection in the chronic rejection model. The effect of HIF-1alpha overexpression was investigated by adeno-assocated virus 2 (AAV2)-mediated gene transfer of a constitutively stabilized form of mouse HIF-1alpha (AAV-HIF 1alpha). The analysis of allografts was based on histology, immunohistochemistry and quantitative reverse transcript-polymerase chain reaction (RT-PCR). RESULTS: Acute and chronic rejection significantly induced HIF-1alpha mRNA in rat cardiac allografts when compared with syngeneic controls. Immunohistochemistry localized significantly increased HIF-1alpha immunoreactivity to vascular smooth muscle cells, vascular endothelial cells, post-capillary venules and graft-infiltrating mononuclear inflammatory cells of the allograft, whereas expression in cardiomyocytes remained unchanged. Regression analysis revealed a linear correlation between the progression of cardiac allograft vasculopathy (CAV) and HIF-1alpha immunoreactivity in post-capillary venules and graft-infiltrating mononuclear inflammatory cells in chronically rejecting rat cardiac allografts. AAV-HIF-1alpha enhanced cardiomyocyte HIF-1alpha production and significantly reduced cardiomyocyte apoptosis and the development of CAV in chronically rejecting rat cardiac allografts. CONCLUSIONS: We found that acute and chronic rejection increased HIF-1alpha mRNA and protein levels in rat cardiac allografts. On the other hand, cardiomyocyte-targeted HIF-1alpha gene transfer inhibited cardiomyocyte apoptosis and the development of CAV, suggesting a novel therapeutic strategy for HIF-1alpha in cardiac allografts. PMID- 20580264 TI - Long-term outcomes in pulmonary arterial hypertension in the first-line epoprostenol or first-line bosentan era. AB - BACKGROUND: The aim of this study was to describe the long-term outcomes in idiopathic pulmonary arterial hypertension (IPAH) treated with first-line bosentan or intravenous (IV) epoprostenol, and additional therapy as needed. METHODS: In a single-center, retrospective, longitudinal cohort, data on right heart catheterization, 6-minute walk distance (6MWD), disease progression and mortality were collected. Outcomes were assessed in first-line bosentan and first line epoprostenol patients. To reduce selection bias due to differences between groups, two independent analyses were performed. First, a comparison was made of World Health Organization (WHO) Functional Class (FC) III patients. Second, to control for disease severity, a matched-pairs analysis was performed, with matching according to baseline cardiac output and exercise capacity and irrespective of FC at baseline. RESULTS: Thirty-seven IPAH patients initiated first-line bosentan treatment and 37 first-line IV epoprostenol. Twenty-nine of the bosentan patients and 16 of the IV epoprostenol patients were in WHO FC III; demographic profiles were similar, although hemodynamic measurements and 6MWD suggested more severe disease in the IV epoprostenol group at treatment initiation. At 1 and 3 years, median change in 6MWD for patients initiating bosentan was +54 m (95% confidence interval: -3 to 76) and +71 m (-123 to 116), respectively, and +92 m (17 to 128) and +142 m (-6 to 242) for those on IV epoprostenol. Absence of disease progression of WHO FC III at 1 and 3 years was 72% and 45% with bosentan and 75% and 44% with IV epoprostenol, respectively. Survival at 1 and 3 years was 93% and 89% with bosentan and 94% and 75% with IV epoprostenol, respectively. Results were confirmed in matched-pairs analysis of 16 bosentan and 16 IV epoprostenol patients with similar disease severity. CONCLUSIONS: First-line epoprostenol treatment may lead to greater improvement in exercise capacity than first-line bosentan. However, these greater exercise improvements did not translate into longer time to disease progression or survival. PMID- 20580266 TI - What they say versus what we see: "hidden" distress and impaired quality of life in heart transplant recipients. AB - BACKGROUND: Quality of life (QoL) studies in heart transplant recipients generally rely on quantifiable self-report questionnaires and have shown that approximately 20% of patients undergo distress and poor QoL not clearly related to medical variables. METHODS: Building on existing qualitative research, we used a phenomenologically informed audiovisual method to explore the nature of "distress" in heart transplant recipients. Focused open-ended interviews were conducted in non-clinical settings with 27 medically stable heart transplant recipients (70% male, mean age 53 +/- 13 years, range 18 to 72 years; mean time since transplant 4.1 +/- 2.4 years). Interviews were audio/videotaped and transcribed verbatim. A qualitative software program (NVIVO8) was used to code interview transcripts and videotaped bodily gestures and "expressive artifacts" as well as vocal tone and volume. RESULTS: Distress was displayed by 88% of patients during the interview, and 52% displayed a profound disjunct between the words they used to describe their quality of life (e.g., "wonderful") and their embodied expressions of the same (e.g., protective body posturing, distressed facial expression). Most also expressed significant distress when discussing issues such as the donor and their "gift of life," as well as a disrupted sense of bodily integrity and identity that they felt could only be appreciated by fellow heart recipients. CONCLUSIONS: Increased awareness of this distress and disruption related to bodily integrity and identity after heart transplant may allow transplant professionals and researchers to see beyond "words" to more effectively reduce distress and improve quality of life. PMID- 20580265 TI - Early adverse events as predictors of 1-year mortality during mechanical circulatory support. AB - BACKGROUND: Ventricular assist devices (VADs) provide effective treatment for end stage heart failure; however, most patients experience > or =1 major adverse events (AEs) while on VAD support. Although early, non-fatal AEs may increase the risk of later death during VAD support, this relationship has not been established. Therefore, we sought to determine the impact on 1-year mortality of AEs occurring during the first 60 days of VAD support. METHODS: A retrospective analysis was performed using prospectively collected data from a single-site database for patients aged > or =18 years receiving left ventricular or biventricular support during 1996 to 2008 and who survived >60 days on VAD support. Fourteen major classes of AEs occurring during this 60-day period were examined. One-year survival rates of patients with and without each major AE were compared. RESULTS: The study included 163 patients (80% men; mean age, 49.5 years), of whom 87% were European American, 72% had left ventricular support, and 83% were bridge to transplant. The occurrence of renal failure, respiratory failure, bleeding events, and reoperations during the first 60 days after implantation significantly increased the risk of 1-year mortality. After controlling for gender, age, VAD type, and intention to treat, renal failure was the only major AE significantly associated with later mortality (hazard ratio, 2.96; p = .023). CONCLUSIONS: Specific AEs, including renal failure, respiratory and bleeding events, and reoperations, significantly decrease longer-term survival. Renal failure conferred a 3-fold increased risk of 1-year mortality. Peri-operative management should focus on strategies to mitigate risk for renal failure in order to maximize later outcomes. PMID- 20580267 TI - Comparison of bronchiolitis obliterans syndrome to other forms of chronic lung allograft dysfunction after lung transplantation. AB - BACKGROUND: The radiographic presence of allograft infiltrates is atypical of bronchiolitis obliterans (BO) and inconsistent with the definition of bronchiolitis obliterans requires that restrictive processes are ruled out. The natural history of these other forms of chronic allograft dysfunction has not been well characterized. We examined the prognostic significance of radiographic and spirometric restrictive processes in comparison to BOS among lung transplant recipients. METHODS: We performed a retrospective review of lung transplant recipients with chronic lung allograft dysfunction (CLAD) as defined by spirometry. Subgroups based on the presence or absence of persistent radiographic abnormalities were labeled as non-specific (CLAD-NS) and CLAD due to BOS (CLAD BOS), respectively. The CLAD-BOS group was further divided into obstructive (OBOS) and restrictive (RBOS) phenotypes based on spirometry. Groups were compared with respect to survival and decline in forced expiratory volume in 1 second (FEV(1)). RESULTS: Among 241 lung transplant recipients, 96 (40%) were identified as having CLAD, of whom 62 (65%) had CLAD-BOS and 34 (35%) CLAD-NS. No difference between groups was identified with respect to post-CLAD survival or decline in FEV(1). CLAD-BOS subgroups included 35 (56%) patients with OBOS and 27 (44%) with RBOS. There was no difference in these subgroups with respect to survival or subsequent FEV(1) decline. CONCLUSIONS: Patients with CLAD and persistent radiographic infiltrates have a similar prognosis to BOS patients but may still represent a clinically distinct phenotype. BOS patients frequently exhibited a restrictive pattern on spirometry, which also did not offer further prognostic information, but could still represent a unique disease phenotype. PMID- 20580268 TI - Subjective reports of stimulus, response, and decision times in speeded tasks: how accurate are decision time reports? AB - Four experiments examined how accurately participants can report the times of their own decisions. Within an auditory reaction time (RT) task, participants reported the time at which (a) the tone was presented, (b) they decided on the response, or (c) the response key was pressed. Decision time reports were checked for plausibility against the actual RTs, and we compared the effects of experimental manipulations on these two measures to see whether the reported decision times showed appropriate effects. In addition, we estimated the amount of error associated with individual decision time reports by checking how often participants' decision time reports were implausibly early (i.e., before stimulus onset) or late (i.e., after response), and by using several quantitative models. Overall, the results suggest that decision time reports are not very accurate but they may be usable for some purposes. PMID- 20580269 TI - A high-loaded hemisphere successfully ignores distractors. AB - We used a response competition paradigm to investigate whether a distractor is effectively rejected under conditions where it is projected to a highly-loaded hemisphere. In two experiments we asked right-handed participants to identify a target among five task-relevant letters while they ignored a distractor. We manipulated both the distractor visual-field (low-load/high-load) and the compatibility of the target and the distractor. In the low-loaded visual-field, we presented a distractor with one task-relevant stimulus to one visual-field and the remaining task-relevant stimuli to the opposite visual-field. In the high loaded visual-field, we presented a distractor and task-relevant stimuli in reverse. In Experiment 1 (left/right), we found a compatibility effect for the low-loaded, but not for the high-loaded visual-field. In Experiment 2, this modulation of the compatibility effect did not appear when the upper/lower visual field was manipulated. These findings demonstrate that a distractor is successfully ignored when it is presented to a highly-loaded hemisphere. PMID- 20580270 TI - Understanding low-income, minority older adult self-perceptions of HIV risk. AB - The number of people ages 50 or older living with HIV in the United States is increasing. Yet, few older adults see themselves at risk of infection. This study examines the heuristic reasoning that low income, minority adults, ages 50 or older use in calculating the likelihood of infection. The data are drawn from face-to-face interviews with a sample of 134 African American and Latino residents, ages 50 to 86, living in low-income housing in Chicago, Illinois, and Hartford, Connecticut. Results show that nearly half of the study's participants thought themselves to be at some level of risk for HIV. In self-assessing their risk, they relied on seven heuristic categories: self-imperilment, social imperilment, fate, incidental contact, situational safety, medical iatrogenesis, and self-protection. These findings extend our understanding of how individuals make sense of their likelihood of experiencing a major health threat and provide insight into more effective HIV prevention programming for older adults. PMID- 20580271 TI - Bimodal ultradian seizure periodicity in human mesial temporal lobe epilepsy. AB - BACKGROUND: Mesial temporal lobe epilepsy (mTLE) has been suggested to follow a circadian rhythm. Previous research found an afternoon peak in mTLE seizure occurrence. We evaluated the pattern of seizure occurrence in patients with well localized mTLE and hypothesized that peak seizure frequency would occur in the afternoon, and that this pattern would not be altered by age, gender, or seizure focus. METHODS: We retrospectively identified consecutive mTLE patients with a seizure-free outcome following anterior temporal lobectomy from 1993 to 2004 with video-EEG captured seizures. We recorded and plotted the 24-h clock time for each seizure and performed cosinor analysis. SAS Proc GLIMMIX was used to fit the linearized transform of the cosinor model. Negative binomial regression fitted by the generalized estimating equations (GEE) method was also performed to estimate and compare the mean seizure rates over a 24-h day. RESULTS: Sixty mTLE patients monitored between 2 and 16 days were analyzed. Mean (standard deviation), median number of seizures per subject were 10.47(7.86), 9.00. Cosinor plots indicated that the function had two modes: 7-8 a.m. and 4-5 p.m. GEE analysis was consistent with peak seizure frequency occurrence at 6-8 a.m. (p<0.0001) and 3-5 p.m. (p<0.01). CONCLUSIONS: We found a bimodal pattern of seizure occurrence in human mTLE, with peak seizure frequencies occurring between 6-8 a.m. and 3-5 p.m. confirming an afternoon peak, as well as a previously unsuspected morning peak in seizure occurrence that provides rationale for future investigations of antiepileptic drug chronopharmacology and informs patient counseling regarding patterns of seizure occurrence. PMID- 20580272 TI - The ubiquitin-proteasome system in prostate cancer and its transition to castration resistance. AB - Prostate cancer is the most common carcinoma in the male population. In its initial stage, the disease is androgen-dependent and responds therapeutically to androgen deprivation treatment but it usually progresses after a few years to an androgen-independent phase that is refractory to hormonal manipulations. The proteasome is a multi-unit protease system that regulates the abundance and function of a significant number of cell proteins, and its inhibition results in cancer cell growth inhibition and apoptosis and is already exploited in the clinic with the use of proteasome inhibitor bortezomib in multiple myeloma. In order to be recognized by the proteasome, a target protein needs to be linked to a chain of the small protein ubiquitin. In this paper, we review the role of ubiquitin-proteasome system (UPS) in androgen receptor-dependent transcription as well as in the castration resistant stage of the disease, and we discuss therapeutic opportunities that UPS inhibition offers in prostate cancer. PMID- 20580273 TI - Smoking cessation has no influence on quality of life in patients with peripheral arterial disease 5 years post-vascular surgery. AB - OBJECTIVES: Smoking is an important modifiable risk factor in patients with peripheral arterial disease (PAD). We investigated differences in quality of life (QoL) between patients who quitted smoking during follow-up and persistent smokers. DESIGN: Cohort study. METHODS: Data of 711 consecutively enrolled patients undergoing vascular surgery were collected in 11 hospitals in the Netherlands. Smoking status was obtained at baseline and at 3-year follow-up. A 5 year follow-up to measure QoL was performed with the EuroQol-5D (EQ-5D) and Peripheral Arterial Questionnaire (PAQ). RESULTS: After adjusting for clinical risk factors, patients, who quit smoking within 3 years after vascular surgery, did not report an impaired QoL (EQ-5D: odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.28-1.43; PAQ: OR = 0.76, 95% CI = 0.35-1.65; visual analogue scale (VAS): OR = 0.88, 95% CI = 0.42-1.84) compared with patients, who continued smoking. Current smokers were significantly more likely to have an impaired QoL (EQ-5D: OR = 1.86, 95% CI = 1.09-3.17; PAQ: OR = 1.63, 95% CI = 1.00-2.65), although no differences in VAS scores were found (OR = 1.17, 95% CI = 0.72-1.90). CONCLUSIONS: There was no effect of smoking cessation on QoL in PAD patients undergoing vascular surgery. Nevertheless, given the link between smoking, complications and mortality in this patient group, smoking cessation should be a primary target in secondary prevention. PMID- 20580274 TI - Endodontic treatment of immature maxillary lateral incisor with two canals: type 3 dens invaginatus. AB - Dens invaginatus is a developmental anomaly. The nonsurgical endodontic treatment of a type 3 dens invaginatus with a large periradicular lesion in a maxillary left lateral incisor of a 10-year-old girl is presented. In spite of difficult diagnosis and treatment of type 3 dens invaginatus, nonsurgical treatment was performed successfully. Resolution of the periradicular lesion and apical closure was observed after 1-year follow-up. PMID- 20580275 TI - Buccal pad of fat and its applications in oral and maxillofacial surgery: a review of published literature (February) 2004 to (July) 2009. AB - This review of the literature was performed to study the frequency and preference of usage of the buccal fat pad (BFP) in oral and maxillofacial reconstruction and to determine its potential versatility in various clinical applications. A computerized literature search using Medline, the JGate@Helinet database, and the Google internet search engine was performed for all relevant articles with specific keywords from February 2004 to July 2009. Focus was on the use of BFP regarding size, location, and types of defects and success and failure rates for various applications. It was found that BFP has been used most commonly for closure of oroantral communications/fistula, followed by reconstruction of maxillary defects; with closure of primary clefts, coverage of mucosal defects, etc. being other uses. Studies suggested that owing to favorable anatomic location, high vascularity, ease of handling, and low failure rate, the BFP has become the flap of choice for reconstruction of various oral defects. The size limitation of the BFP must be known to permit successful outcome. The results have been encouraging for clinicians to make use of potential benefits of the BFP in closure of defects in the oral and maxillofacial region. PMID- 20580276 TI - Should warfarin be discontinued before a dental extraction? A decision-tree analysis. AB - OBJECTIVE: The aim of this study was to determine if warfarin should be withdrawn before a single tooth extraction on a patient with a prosthetic heart valve. STUDY DESIGN: A quantitative decision tree was constructed to assess the expected utility values of 2 typical strategies to manage the dental extraction on a patient currently medicated with warfarin. Probabilities and utilities for a cardiovascular accident and major bleeding from a dental extraction were taken from the literature. RESULTS: The decision slightly favors withholding warfarin: generating an optimal expected utility value of 0.976 utile. This was only 0.02 utile higher than the alternative option of continuing warfarin for a dental extraction. CONCLUSION: The decision to withhold or continue warfarin before a dental extraction depends more on the relative risk of a major bleeding between the 2 medical management strategies than on the consequences of a cardiovascular accident. PMID- 20580277 TI - Shaping canals with ProFiles and K3 instruments: does operator experience matter? AB - OBJECTIVE: The aim of this study was to determine the influence of operator experience on the shaping ability of ProFile and K3 nickel-titanium rotary instruments in simulated root canals. STUDY DESIGN: One hundred sixty simulated canals consisting of 4 different shapes in terms of angle and position of curvature were prepared by experienced and inexperienced operators. One experienced operator prepared 80 canals and 2 inexperienced operators prepared 80 canals with a crown-down technique using either ProFile or K3 .06 taper instruments. Images of the canals were taken, using a camera attached to a computer with image analysis software, before surgery and after preparation to sizes 20, 25, and 30 to working length. Postoperative images were combined with the preoperative image to highlight the amount and position of material removed during preparation as well as the shape of the prepared canal. RESULTS: Overall, there was a highly statistically significant difference (P<.001) between the instruments for the time taken to prepare the canals, with K3 instruments taking a mean of 4.9 minutes and ProFile 6.0 minutes. Six instruments fractured (3 in each operator category); 4 were ProFile instruments. Four instruments deformed, all with the inexperienced operators; 3 were K3. No perforations or zips were observed; however, 1 danger zone (created by the experienced operator using K3 instruments) and 1 ledge (created by an inexperienced operator using K3 instruments) were created. Twelve outer widenings were created with a highly significant difference (P<.001) between the operator and instrument used. There was a highly significant difference by instrument (P<.001), and experience (P=.008) regarding absolute transportation at the beginning of the curve and a statistically significant difference (P=.031) for the instrument used regarding absolute transportation half way to the orifice. CONCLUSION: The experienced operator prepared canals more quickly and safely than the inexperienced operators when using K3 instruments; both used ProFile instruments quickly and safely. Inexperienced operators would be advised to train using less aggressive instruments and when confident could progress to other instrument designs. PMID- 20580278 TI - Intraosseous ameloblastoma. AB - Ameloblastomas are benign slow-growing aggressive neoplasms with a poorly understood potential for rare metastasis. They are capable of reaching large sizes with extensive local bone erosion and destruction. They are composed of a mixture of ameloblastic epithelium and mesenchyme and arise from rests of outer and inner enamel epithelium and dental lamina. Microscopically, ameloblastomas are recognizable from their recapitulation of embryologic ameloblasts and stellate reticulum. There are 3 subtypes: the conventional or solid-multicystic variant, the unicystic variant, and the desmoplastic variant. Treatment planning for a given tumor includes consideration of location, primary versus recurrent, size, presence of cortical perforation, and age and health of the patient. Complete excision is recommended for conventional and desmoplastic variants. The unicystic variant requires additional subtyping to determine the best treatment approach. PMID- 20580279 TI - A comparison of bone generation capability in rabbits using tooth ash and plaster of Paris with platelet-rich plasma or fibrin sealant. AB - OBJECTIVES: Increased attention has been focused on determining the most efficacious materials for generalized bone grafts. This article presents the results of a histomorphometric analysis of bone healing in the calvaria of rabbits. The study compared the use of a tooth ash and plaster of Paris mixture alone, in association with platelet-rich plasma (PRP), and in association with fibrin sealant. STUDY DESIGN: Twelve rabbits were divided into control (group 1) and experimental groups (groups 2, 3, and 4). Group 1 was maintained as an unfilled control, and tooth ash and plaster of Paris were used in group 2, tooth ash and plaster of Paris with PRP were used in group 3, and tooth ash and plaster of Paris with fibrin sealant (Tissucol Duo Quick) were used in group 4. One-half of the animals were killed after 4 weeks, and the rest were killed after 8 weeks. Bone samples were taken from the defect areas, and newly formed bone was analyzed histomorphometrically. RESULTS: The rate of new bone formation in groups 2, 3, and 4 was significantly higher than the rate in the control group. The rate of new bone formation in groups 3 and 4 was higher than the rate in group 2, but the difference was not statistically significant. CONCLUSION: The concomitant use of PRP or fibrin sealant with tooth ash and plaster of Paris graft materials may have a positive effect on bone healing. PMID- 20580280 TI - Two- and three-dimensional evaluation of the upper airway after bimaxillary correction of Class III malocclusion. AB - OBJECTIVE: The aim the study was to evaluate area and volumetric changes in the upper airway after bimaxillary correction of Class III malocclusion by the means of computer tomography (CT), and to compare these to the changes in linear measurements from lateral cephalograms. STUDY DESIGN: This was a prospective clinical trial. Lateral cephalograms and CT scans of 10 Class III patients were evaluated 1 week before and 6 months after surgery. Wilcoxon matched pairs signed ranks test was used to determine the differences in measurements pre- and postoperatively. Spearman's rank correlation was used to test the association between the CT and cephalometric measurements. RESULTS: CT measurements: The oropharyngeal and hypopharyngeal volumes increased by 3.98 +/- 4.18 cm(3) (P = .015) and 2.51 +/- 1.92 cm(3) (P = .021), respectively. The total volume of the posterior airway space increased, but the increase was not statistically significant. After surgery no change in the cross-sectional area of the upper airway was recorded at the retropalatal, oropharyngeal, or hypopharyngeal levels. Cephalometric measurements: The nasopharyngeal space increased 4.08 +/- 5.07 mm (P = .039) and the tongue increased in length by 4.84 +/- 5.93 mm (P = .22). No correlation was found between the measurements on CT scans and corresponding measurements on the lateral cephalograms. CONCLUSIONS: Bimaxillary surgery for correction of Class III malocclusion did not cause decrease of the posterior airway space. Three-dimensional imaging techniques are preferable to 2 dimensional lateral cephalograms for evaluation of the upper airway after orthognathic procedures. PMID- 20580281 TI - HSP 60 expression in recurrent oral ulcerations of Behcet's disease. AB - OBJECTIVE: The aim was to investigate heat shock protein 60 (HSP60) expression in oral ulcerations of Behcet's disease (BD). STUDY DESIGN: Biopsy specimens were obtained from patients with BD (n = 11), recurrent aphthous stomatitis (RAS) (n = 11), oral lichen planus (OLP) (n = 11) and healthy individuals (HI) (n = 11). Eight samples in BD and RAS groups were evaluable. All groups were analyzed by biotin streptavidin-aminoethylcarbazole using monoclonal mouse antibodies to HSP60 Ab-1 (clone LK1). RESULTS: Immunostaining indicative of HSP60 expression in BD and RAS were significantly higher than HI. No significant difference was found between BD and OLP except in the suprabasal layer of epithelium. CONCLUSIONS: Altered expression of HSP60 was found in ulcerative lesions of BD and RAS suggesting that HSP60 has an association with the etiology or chronicity of these inflammatory lesions. PMID- 20580282 TI - Pathogenesis of sialadenosis: possible role of functionally deficient myoepithelial cells. AB - OBJECTIVES: The pathogenesis of acinar enlargement in sialadenosis is obscure. As myoepithelial cells had been reported to show degenerative changes, we decided to investigate the possible role of functionally deficient myoepithelial cells in the development of sialadenosis. STUDY DESIGN: This study was a morphometric analysis of glands immunohistochemically stained for CK14, alpha-actin, and Ki67 in 10 cases of sialadenosis and 11 normal parotids. RESULTS: In sialadenosis, acini were much larger; there was a minor decrease in the density of the distribution of myoepithelial cells stained for CK14 and a major decrease in the density of the distribution and thickness of the myofilament component of myoepithelial cells stained for alpha-actin; and the proliferation of acinar and myoepithelial cells was reduced. CONCLUSIONS: Our results demonstrate a major loss and thinning of the myofilament component of the myoepithelial cells and thereby a loss of mechanical support for the acini in sialadenosis. This possibly allows acinar cells to expand as secretory granules accumulate intracellularly to produce the great acinar enlargement. This functional myoepithelial insufficiency is possibly a consequence of an autonomic neuropathy secondary to severe metabolic or hormonal disorders. PMID- 20580283 TI - Pseudoaneurysm of the facial artery as a late complication of bilateral sagittal split osteotomy and facial trauma. AB - Pseudoaneurysms, or arteriovenous fistulas, of the extracranial arterial system, particularly the facial artery, are rare. Its occurrence after reconstructive facial surgery has been reported rarely in the literature. In this article we describe a rare case of pseudoaneurysm developing over 4 weeks after an uneventful Le Fort I maxillary osteotomy, sagittal split osteotomy, and advancement genioplasty. A 22-year-old man presented with a severe class III skeletal deformity, mandibular hyperplasia, and maxillary hypoplasia. The patient's immediate postoperative course was uneventful for a 2-week period after surgery. Then the patient, while at home, experienced an accidental injury to his jaw and started to bleed from his left retromandibular side. He was taken to a local hospital where his bleeding was controlled by topical coagulant and pressure. During this short hospital visit he was given 3 units of blood and was subsequently discharged. He had no further bleeding and was monitored on a regular basis. One month after his double jaw surgery and 2 weeks after his bleeding episode, the left facial swelling diminished in size but was still visible. This mass was soft and pulsatile with a palpable thrill and auditory machinery murmur on auscultation. Although the patient was totally asymptomatic at this time, he was sent to the emergency room for a computerized tomography scan with 3-dimensional reconstruction. A Doppler ultrasound was also ordered. The ultrasound revealed the mass to be a pseudoaneurysm. Angiography revealed a pseudoaneurysm of the left facial artery. Coil embolization of the left facial artery was performed with a Cordis Trufill complex coil. The patient tolerated the procedure well and a repeat angiogram demonstrated no further evidence of aneurysm, arteriovenous malformation, vasospasm, or feeding branches to the fistula. The patient made an uneventful recovery and was discharged the day after the procedure. In this article, we review the anatomy of the extracranial arterial system of the head and neck, discuss the pathogenesis and clinical presentation of pseudoaneurysm, and present diagnostic imaging and treatment options for pseudoaneurysms of the face. PMID- 20580284 TI - A new management approach for dental treatment after a cerebrovascular event: a comparative retrospective study. AB - OBJECTIVE: Current literature recommends postponing dental treatment until 6-12 months after a stroke, based on the presumed risk of recurrent stroke. The purpose of this study was to suggest that the importance of dental care during this period exceeds the risk of medical complications in this patient population. STUDY DESIGN: Two groups were compared: 1) a cerebrovascular (CrbV) study group: patients (n = 16) who had suffered from a CrbV event within the 12 months preceding their dental procedure; and 2) a cardiovascular (CV) control group: patients (n = 25) suffering from ischemic CV disease. Patients were monitored during and after the dental treatment. Treatment parameters and outcome were compared. RESULTS: Patients received various essential dental treatments with intense monitoring during their dental management. Dental procedures were invasive in 68.8% and 0% of CrbV and CV groups, respectively. Dental treatments were completed uneventfully. No clinical CrbV or CV complications were noted in either group after the dental treatment. CONCLUSION: Within the limits of this small retrospective study, it appears that dental treatment may be safely administered in patients a few weeks after the CrbV event as long as these patients are kept under optimal medical surveillance. PMID- 20580285 TI - Invasive cervical resorption: report on two cases. AB - Invasive cervical resorption is a relatively uncommon form of external root resorption that may lead to tooth loss. This article presents the clinical and radiologic diagnoses and treatment modalities of invasive cervical resorption in 2 patients. In the first case, we did a slow orthodontic forced eruption to make the bone grow coronally. After 6 months, the tooth was extracted and an immediate implant was placed. Eight months later a zirconia crown was cemented. In the second case, we performed root canal treatment followed by a composite reconstruction of the defect. These 2 cases illustrate different approaches based on the extent of the defect. PMID- 20580286 TI - Biomechanical evaluation of a T-shaped miniplate fixation of a modified sagittal split ramus osteotomy with buccal step, a new technique for mandibular orthognathic surgery. AB - OBJECTIVE: The purpose of this study was to biomechanically evaluate the stability of a T-shaped miniplate fixation of a modified sagittal split ramus osteotomy (MSSRO) with buccal step and to compare it with single or double parallel straight miniplates fixing a standard sagittal split ramus osteotomy (SSRO). STUDY DESIGN: Eighteen Synbone mandibular replicas were used in the study and divided into 3 groups. Standard SSRO was applied in the first and second groups, and the third group was cut for MSSRO with buccal step. After 7 mm of advancement, fixation modalities for the 3 groups included a single straight miniplate, double-parallel straight miniplates, and a T-shape miniplate, respectively. Each model was secured in a jig and subjected to vertical load on the anterior teeth. RESULTS: The T miniplate group showed a significantly higher value for stability than the group with a single straight miniplate. There was no significant difference in stability between the T miniplate and the double parallel straight miniplate groups. CONCLUSION: For mandibular advancement surgery of 7 mm in a laboratory environment, a T-shaped miniplate used with MSSRO and buccal step as a combination significantly optimize the resistance and stability of the fixation compared with a standard SSRO fixed with a single straight miniplate. PMID- 20580287 TI - Pattern of osteogenesis during onlay bone graft healing. AB - OBJECTIVE: The aim of this paper was to analyze how healing occurs between onlay bone graft and the mandible cortex. STUDY DESIGN: Autologous and allogeneic corticocancellous bones, harvested from the ilium wing, were grafted at each mandible side of 40 rabbits. One side received platelet-rich plasma (PRP). Killings occurred at 3, 7, 14, 28, and 56 days. Tissues were stained by hematoxylin-eosin and toluidine blue. New bone area was measured at different regions of sections stained with toluidine blue. Wilcoxon test was used to analyze differences among regions and Bonferroni test to analyze the influence of PRP, graft nature, and days. RESULTS: Osteogenesis was higher at the lateral region (P < .05). PRP tended to improve bone neoformation, which was higher at the allogeneic graft. Statistical significance among the different categories of variables-grafts, use of PRP, and days of observation-did not have a linear behavior. A linear behavior of statistical tests was not detected. Bone new formation increased until the 14th day (P < .05). CONCLUSIONS: Onlay grafts heal due to osteogenesis which occurs at the lateral region and between the cortex and host mandible. Allogeneic grafts and PRP tend to improve bone formation. PMID- 20580288 TI - Neurosensory impairment of the mental nerve as a sequel of periapical periodontitis: case report and review. AB - Apical periodontitis of endodontic origin rarely leads to sensory impairment of the inferior alveolar or mental nerve. This article reviews and documents a clinical case of neurological disorder where paresthesia and hypesthesia of the mental nerve resulted as a sequel of apical periodontitis of a mandibular second premolar. The healing process and long-term results 3 years after conventional root canal treatment are presented. PMID- 20580289 TI - Novel large deletions in the human alpha-globin gene cluster: Clarifying the HS 40 long-range regulatory role in the native chromosome environment. AB - Globin genes, which encode the protein subunits of hemoglobin (Hb), are organized in two different gene clusters and present a coordinated and differential pattern of expression during development. Concerning the human alpha-globin gene cluster (located at chromosome region 16p13.3), four upstream highly conserved elements known as multispecies conserved sequences (MCS-R1-4) or DNase I hypersensitive sites (HSs) are implicated in the long-range regulation of downstream gene expression. However, only the absence of the MCS-R2 site (HS-40) has proven to drastically downregulate the expression of those genes, and consequently, it has been regarded as the major and crucial distal regulatory element. In this study, Multiplex Ligation-dependent Probe Amplification was used to screen for deletions in the telomeric region of the short arm of chromosome 16, in an attempt to explain the alpha-thalassemia or the HbH disease present in a group of Portuguese patients. We report four novel and five uncommon deletions that remove the alpha globin distal regulatory elements and/or the complete alpha-globin gene cluster. Interestingly, one of them occurred de novo and removes all HSs except HS-10, while other eliminates only the HS-40 site, the latter being replaced by the insertion of a 39 nucleotide orphan sequence. Our results demonstrate that HS-10 alone does not significantly enhance the alpha-globin gene expression. The absence of HS-40 in homozygosity, found in a patient with Hb H disease, strongly downregulates the expression of alpha-globin genes but it is not associated with a complete absence of alpha-globin chain production. The study of naturally occurring deletions in this region is of great interest to understand the role of each upstream regulatory element in the native human erythroid environment. PMID- 20580290 TI - Runx2 in normal tissues and cancer cells: A developing story. AB - The Runx transcription factors are essential for mammalian development, most notably in the haematopoietic and osteogenic lineages. Runx1 and its binding partner, CBFbeta, are frequently targeted in acute leukaemia but evidence is accumulating that all three Runx genes may have a role to play in a wider range of cancers, either as tumour promoters or tumour suppressors. Whilst Runx2 is renowned for its role as a master regulator of bone development we discuss here its expression pattern and putative functions beyond this lineage. Furthermore, we review the evidence that RUNX2 promotes neoplastic development in haematopoietic lineages and in advanced mammary and prostate cancer. PMID- 20580291 TI - Infections caused by fungi of the Scedosporium/Pseudallescheria complex in veterinary species. AB - Fungi belonging to the Scedosporium/Pseudallescheria complex (SPCF) have been known to cause human infections for nearly a century and are important human pathogens, with an increasing frequency of infection in patients with underlying conditions. There appears to be a lower incidence of infections with SPCF in veterinary species, although this may be related to a lack of awareness of these diseases. Important recent taxonomic changes in this group of fungi include the classification of Pseudallescheria boydii and Scedosporium apiospermum as two distinct species and the identification of new pathogenic species of SPCF. In this article, the literature on natural and experimental infections caused by SPCF in veterinary species is reviewed. The importance of an accurate identification of veterinary isolates by molecular methods is stressed, especially since virulence and susceptibility to antimycotic drugs of different species may vary. PMID- 20580292 TI - ERIC-PCR genotyping of Haemophilus parasuis isolates from Brazilian pigs. AB - Among 63 Haemophilus parasuis isolates from 17 Brazilian pig herds, 33 genotypes were identified by enterobacterial repetitive intergenic consensus (ERIC)-PCR, with a diversity index of 0.96. Eight serovars were detected, with serovar 4 (15.9%) being most frequent; 60.3% of isolates were non-typeable. There was no strong association between site of isolation and genotype or serovar. PMID- 20580293 TI - Vaccinating pigs against Mycoplasma hyopneumoniae infection: failure to prevent transmission. PMID- 20580294 TI - Optimizing gradient waveforms for microstructure sensitivity in diffusion weighted MR. AB - Variations in gradient waveforms can provide different levels of sensitivity to microstructure parameters in diffusion-weighted MR. We present a method that identifies gradient waveforms with maximal sensitivity to parameters of a model relating microstructural features to diffusion MR signals. The method optimizes the shape of the gradient waveform, constrained by hardware limits and fixed orientation, to minimize the expected variance of parameter estimates. The waveform is defined discretely and each point optimized independently. The method is illustrated with a biomedical application in which we maximize the sensitivity to microstructural features of white matter such as axon radius, intra-cellular volume fraction and diffusion constants. Simulation experiments find that optimization of the shape of the gradient waveform improves sensitivity to model parameters for both human and animal MR systems. In particular, the optimized waveforms make axon radii smaller than 5 microm more distinguishable than standard pulsed gradient spin-echo (PGSE). The identified class of optimized gradient waveforms have dominant square-wave components with frequency that increases as the radius size decreases. PMID- 20580295 TI - 1H-14N HSQC detection of choline-containing compounds in solutions. AB - Choline nitrogen ((14)N) has a long relaxation time (seconds) which is due to the highly symmetric chemical environments. (14)N in choline also has coupling constants with protons (0.6 Hz to methyl protons, 2.7 Hz to CH(2)O protons and 0.2 Hz to NCH(2) protons). Based on these properties, we introduce a two dimensional NMR method to detect choline and its derivatives in solutions. This method is the (1)H-(14)N hetero-nuclear single-quantum correlation (HSQC) experiment which has been developed in solid-state NMR in recent years. Experiments have demonstrated that the (1)H-(14)N HSQC technique is a sensitive method for detection of choline-containing compounds in solutions. From 1mM choline solution in 16 min on a 500 MHz NMR spectrometer, a (1)H-(14)N HSQC spectrum has been recorded with a signal-to-noise ratio of 1700. Free choline, phosphocholine and glycerophosphocholine in milk can be well separated in (1)H (14)N HSQC spectra. This technique would become a promising analytical approach to mixture analyses where choline-containing compounds are of interest, such as tissue extracts, body fluids and food solutions. PMID- 20580296 TI - Structure-based design of carbon nanotubes as HIV-1 protease inhibitors: atomistic and coarse-grained simulations. AB - Nanoparticles such as fullerenes and carbon nanotubes have been extensively studied for biomedical applications. In this paper, we report the design of carbon nanotubes as HIV-1 protease inhibitors. Docking and molecular dynamics calculations are performed using an atomistic model to explore the optimal interaction structure and free energy between the nanotube and HIV-1 protease. A coarse-grained model is then developed based on the atomistic model, allowing us to investigate the dynamic behaviors of the protease in the bound and unbound states. The dynamic process reveals that the carbon nanotube is able to bind to the active site of the protease and prevent the active flaps from opening up, thus blocking the function of the protease. This process is strongly influenced by the size of the nanotube. The binding of carbon nanotubes to an alternative binding site other than the active site is also explored. Therefore, carbon nanotube-based inhibitors have great potential for application as HIV-1 protease inhibitors. PMID- 20580297 TI - Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice. AB - A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid beta-oxidation defect. Beneficial effects have been reported with an MCT-bolus prior to exercise. Little is known about the impact of a long-term MCT diet on hepatic lipid metabolism. Here we investigate the effects of MCT-supplementation on liver and blood lipids in the murine model of VLCADD. Wild-type (WT) and VLCAD knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5weeks, (2) an MCT diet over 5 weeks and (3) an LCT diet plus MCT-bolus. Blood and liver lipid content were determined. Expression of genes regulating lipogenesis was analyzed by RT-PCR. Under the LCT diet, VLCAD-KO mice accumulated significantly higher blood cholesterol concentrations compared to WT mice. The MCT-diet induced severe hepatic steatosis, significantly higher serum free fatty acids and impaired hepatic lipid mobilization in VLCAD-KO mice. Expression at mRNA level of hepatic lipogenic genes was up-regulated. The long-term MCT diet stimulates lipogenesis and impairs hepatic lipid metabolism in VLCAD-KO mice. These results suggest a critical reconsideration of a long-term MCT-modified diet in human VLCADD. In contrast, MCT in situations of increased energy demand appears to be a safer treatment alternative. PMID- 20580298 TI - Polymerase chain reaction survey of feline haemoplasma infections in Greece. AB - The aim of this study was to use real-time polymerase chain reaction assays to determine the prevalence of three haemoplasma species in cats from Greece and to evaluate possible associations between haemoplasma infection and age, gender, feline immunodeficiency virus/feline leukaemia virus (FIV/FeLV) status and packed cell volume (PCV). Ninety-seven cats (24 ill anaemic, 55 ill non-anaemic, 18 healthy non-anaemic) were included in the study. Twenty cats (20.6%) were haemoplasma positive; seven cats were infected only with Mycoplasma haemofelis, 10 were infected only with 'Candidatus Mycoplasma haemominutum' and three were co infected with M haemofelis and 'Candidatus M haemominutum'. 'Candidatus Mycoplasma turicensis' was not detected. Haemoplasma infection was associated with older age (P=0.019). M haemofelis infection tended to be more common in anaemic cats (P=0.058). No association between gender and haemoplasma infection, or haemoplasma relative copy number and PCV, was detected. Retroviral infection rates were very low with only one FeLV proviral positive cat found. PMID- 20580299 TI - [Evaluating economic impacts from healthcare research: an unresolved matter]. PMID- 20580300 TI - Lytic lesion in the second metacarpal. PMID- 20580301 TI - [Internship in university hospitals: a necessary experience]. PMID- 20580302 TI - Wall shear stress on LDL accumulation in human RCAs. AB - The blood flow and transportation of molecules in the cardiovascular system plays crucial role in the genesis and progression of atherosclerosis. Atherosclerosis shows predilection in regions of the arterial tree with hemodynamic particularities, as local disturbances of wall shear stress in space, and locally high concentrations of lipoprotein. A semi-permeable nature of the arterial wall computational model is incorporated with hydraulic conductivity and permeability treated as wall shear stress dependent. Six image-based human diseased right coronary arteries (RCA) are used to elucidate the low-density lipoprotein (LDL) transport. The 3D reconstruction technique is a combination of angiography and IVUS. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall. The coupling of fluid dynamics and solute dynamics at the endothelium is achieved by the Kedem Katchalsky equation (water infiltration). The luminal surface LDL concentration at the arterial wall is flow-dependent with local variations due to geometric features. The relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. There is medium correlation (Pearson) between low WSS and high LDL. The degree of elevation in luminal surface LDL concentration is mostly affected by the water infiltration velocity at the vessel wall. Under constant water infiltration the shear dependent endothelial permeability effects, in comparison to those using constant value, are marginal. Area-averaged normalized LDL concentration over the RCAs, using constant water infiltration and endothelial permeability is 3.6% higher than that at the entrance. Area-averaged normalized LDL concentration over the RCAs, using shear dependent water infiltration and endothelial permeability is 9.6%. Perspective computational fluid dynamics users, incorporating mass transfer (LDL) within the blood flow, are forced to treat the problem using shear dependent endothelial values. PMID- 20580303 TI - Myofascial trigger point needling for whiplash associated pain--a feasibility study. AB - Clinicians claim that myofascial trigger points (MTrPs) are a primary cause of pain in whiplash injured patients. Pain from MTrPs is often treated by needling, with or without injection. We conducted a placebo controlled study to test the feasibility of a phase III randomised controlled trial investigating the efficacy of MTrP needling in patients with whiplash associated pain. Forty-one patients referred for physiotherapy with a recent whiplash injury, were recruited. Patients were randomised to receive standardised physiotherapy plus either acupuncture or a sham needle control. A trial was judged feasible if: i) the majority of eligible patients were willing to participate; ii) the majority of patients had MTrPs; iii) at least 75% of patients provided completed self assessment data; iv) no serious adverse events were reported and v) the end of treatment attrition rate was less than 20%. 70% of those patients eligible to participate volunteered to do so; all participants had clinically identified MTrPs; a 100% completion rate was achieved for recorded self-assessment data; no serious adverse events were reported as a result of either intervention; and the end of treatment attrition rate was 17%. A phase III study is both feasible and clinically relevant. This study is currently being planned. PMID- 20580304 TI - Singlet oxygen signaling links photosynthesis to translation and plant growth. AB - Translation is a major target of metabolic and growth control in animals and plants. Changes in the phosphorylation status of ribosomal protein S6 are responsible for rapid adjustments in the growth pattern of higher plants in response to changes in the environment. In this review, we illuminate some common and unique aspects of translational control in animals and plants and discuss recent studies that link photosynthesis to growth via specific signal transduction cascades, one of which relies on singlet oxygen and the plant growth regulator jasmonic acid (JA). It is the aim of this review to discuss the role of the target of rapamycin (TOR) signaling network in plants and what mechanisms could contribute to growth control in response to the changing environment. PMID- 20580305 TI - Segmentation of image ensembles via latent atlases. AB - Spatial priors, such as probabilistic atlases, play an important role in MRI segmentation. However, the availability of comprehensive, reliable and suitable manual segmentations for atlas construction is limited. We therefore propose a method for joint segmentation of corresponding regions of interest in a collection of aligned images that does not require labeled training data. Instead, a latent atlas, initialized by at most a single manual segmentation, is inferred from the evolving segmentations of the ensemble. The algorithm is based on probabilistic principles but is solved using partial differential equations (PDEs) and energy minimization criteria. We evaluate the method on two datasets, segmenting subcortical and cortical structures in a multi-subject study and extracting brain tumors in a single-subject multi-modal longitudinal experiment. We compare the segmentation results to manual segmentations, when those exist, and to the results of a state-of-the-art atlas-based segmentation method. The quality of the results supports the latent atlas as a promising alternative when existing atlases are not compatible with the images to be segmented. PMID- 20580306 TI - Why emergentist accounts of cognition are more theoretically constraining than structured probability accounts: comment on Griffiths et al. and McClelland et al. PMID- 20580307 TI - Viral miRNAs: tools for immune evasion. AB - MicroRNAs (miRNAs) are noncoding RNA molecules approximately 22 nucleotides in length that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. MiRNAs have been identified in a diverse range of both metazoan and plant species. Functionally, miRNAs modulate multiple cellular processes including development, hematopoiesis, immunity, and oncogenesis. More recently, DNA viruses were found to encode and express miRNAs during host infection. Although the functions of most viral miRNAs are not well understood, early analysis of target genes pointed to immune modulation suggesting that viral miRNAs are a component of the immune evasion repertoire, which facilitates viral persistence. In addition to directly targeting immune functions, viral encoded miRNAs contribute to immune evasion by targeting proapoptotic genes, and in the case of herpesviruses, by controlling viral latency. Here we summarize the recently discovered targets of viral miRNAs and discuss the complex nature of this novel emerging regulatory mechanism. PMID- 20580308 TI - Life with eight flagella: flagellar assembly and division in Giardia. AB - Flagellar movement in Giardia, a common intestinal parasitic protist, is crucial to its survival in the host. Each axoneme is unique in possessing a long, cytoplasmic portion as well as a membrane-bound portion. Intraflagellar transport (IFT) is required for the assembly of membrane-bound regions, yet the cytoplasmic regions may be assembled by IFT-independent mechanisms. Steady-state axoneme length is maintained by IFT and by intrinsic and active microtubule dynamics. Following mitosis and before their segregation, giardial flagella undergo a multigenerational division cycle in which the parental eight flagella migrate and reposition to different cellular locations; eight new flagella are assembled de novo. Each daughter cell thus inherits four mature and four newly synthesized flagella. PMID- 20580310 TI - Ulnar neuropathy at the elbow: not simply a compressive neuropathy? PMID- 20580309 TI - Acute hepatitis B infection associated with drug-resistant hepatitis B virus. AB - BACKGROUND: Pre-existing antiviral-resistant hepatitis B virus (HBV) has been associated with primary non-response to lamivudine treatment in patients with chronic hepatitis B, but little is known of the capacity for resistant HBV to cause primary infection. OBJECTIVE: The study was to investigate if Beijing patients with acute hepatitis B (AHB) are infected with drug-resistant HBV. STUDY DESIGN: Sera were collected from 201 NA-untreated patients with AHB. Direct polymerase chain reaction (PCR) sequencing was used to screen HBV reverse transcriptase (RT) domain and clonal sequencing were performed for all resistance positive samples. RESULTS: Direct PCR sequencing showed that 14 samples (7.0%) were positive for drug-resistant HBV variants, comprised of 11 with the lamivudine-resistant pattern rtM204I and/or rtM204V in the presence and absence of compensatory mutations rtL80I, rtV173L, and rtL180M; two with the adefovir resistant pattern rtA181V; and one with the entecavir-resistant pattern rtL180M+rtS202G+rtM204V. Concomitance of resistance variants with wild-type HBV was observed in samples from 13 patients. Clonal sequencing verified direct sequencing results. Furthermore, variants associated with resistance to adefovir or entecavir were found in 3 samples. CONCLUSIONS: Drug-resistant HBV strains, including those not resistant to lamivudine, are transmissible and can cause acute hepatitis B in China. PMID- 20580311 TI - Effect of spinal cord injury and its lesion level on stretch reflex modulation by cold stimulation in humans. AB - OBJECTIVE: To determine how short-latency stretch reflex amplitude in the soleus muscle is modulated by cold stimulation in able-bodied individuals and individuals with complete spinal cord injury. METHODS: An initial 100-s baseline period was followed by 50-s cold stimulation periods. Stretch reflex of the right soleus muscle was elicited for 10-s intervals, while cold stimulation was applied to the left thigh. RESULTS: Peak-to-peak amplitude of the stretch reflex increased significantly during cold stimulation up to 127 +/- 21% of the baseline in the able-bodied group (n=9, P<0.01). Similarly, stretch reflex increased up to 125 +/- 11% in a group with injury level at or below thoracic 10 (n=4), although this increase was not significant. On the other hand, stretch reflex decreased significantly down to 78 +/- 20% in a group with injury level at or above thoracic 6 (n=8, P<0.05). CONCLUSIONS: Effect of afferent inputs induced by cold stimulation on stretch reflex modulation is different depending on the extent of central nervous systems participating in the modulation. SIGNIFICANCE: Our findings provide a better understanding of some basic changes in afferent efferent spinal reflex pathways which are probably not monosynaptic in nature. PMID- 20580312 TI - Deep brain stimulation: can we do it better? PMID- 20580313 TI - The concept of 'Organismic Asymmetry' in sport science. AB - The concept of organismic asymmetry refers to an inherent bias for seeking explanations of human performance and behaviour based on internal mechanisms and referents. A weakness in this tendency is a failure to consider the performer environment relationship as the relevant scale of analysis. In this paper we elucidate the philosophical roots of the bias and discuss implications of organismic asymmetry for sport science and performance analysis, highlighting examples in psychology, sports medicine and biomechanics. PMID- 20580314 TI - Perceived and actual competence among overweight and non-overweight children. AB - Child overweight and obesity continues to be a global public health concern. The aim of this study was to investigate whether children's actual and perceived physical competence and parental perception's of their child's competence differ by weight status. Understanding these differences is important because physical activity levels are significantly lower among overweight children than their lean counterparts and children's motivation to participate in physical activity is influenced by their perceived and actual competence and their parents perceptions of their competence. Cross-sectional data were collected from 1414 9- and 11-year old children and their parents from 20 primary schools in New South Wales, Australia. Outcomes measured included child and parental perceptions of physical competence and children's actual physical competence. Parents of overweight boys perceived them to be significantly less competent than parents of non-overweight boys. For 11-year-old girls, parent's perception of their daughter's ability to run (mean diff=1.06 [95% CI 0.73, 1.40]), jump (mean diff=0.54 [95% CI 0.15, 0.93]) and leap (mean diff=0.78 [95% CI 0.41, 1.17]) was lower among parents of overweight children. Overweight children also reported lower perceived physical competence than non-overweight children. 9- and 11-year-old overweight boys had lower actual physical competence than non-overweight boys (mean diff=1.32 [95% CI 0.29, 2.35]; mean diff=1.26 [95% CI 0.37, 2.15], respectively). Overweight 11 year-old girls had lower actual competence than non-overweight 11-year-old girls (mean diff=1.14 [95% CI 0.70, 2.12]). This study highlighted several differences between overweight and non-overweight children. Better understanding these differences at different stages of development may lead to identifying more specific and appropriate intervention points to promote physical activity in overweight children. PMID- 20580315 TI - The dynamic regulation of microcirculatory conduit function: features relevant to transfusion medicine. AB - The microcirculation is not merely a passive conduit for red cell transport, nutrient and gas exchange, but is instead a dynamic participant contributing to the multiple processes involved in the maintenance of metabolic homeostasis and optimal end-organ function. The microcirculation's angioarchitechture and surface properties influence conduit function and flow dynamics over a wide spectrum of conditions, accommodating many different mechanical, pathological or organ specific responses. The endothelium itself plays a critical role as the interface between tissues and blood components, participating in the regulation of coagulation, inflammation, vascular tone, and permeability. The complex nitric oxide pathways affect vasomotor tone and influence vascular conduit caliber and distribution density, alter thrombotic propensity, and modify adhesion molecule expression. Nitric oxide pathways also interact with red blood cells and free hemoglobin moieties in normal and pathological conditions. Red blood cells themselves may affect flow dynamics. Altered rheology and compromised NO bioavailability from medical storage or disease states impede microcirculatory flow and adversely modulate vasodilation. The integration of the microcirculation as a system with respect to flow modulation is delicately balanced, and can be readily disrupted in disease states such as sepsis. This review will provide a description of these varied and intricate functions of the microvasculature. PMID- 20580316 TI - A Turkish version of myocardial infarction dimensional assessment scale (TR MIDAS): reliability-validity assesment. AB - BACKGROUND: Many new measuring devices have been developed so that broader psychometric measurements in the coronary artery disease, disease-specific health status measurements, and identification of the broader quality of life can be performed in the recent years. AIMS: The study was intended to determine whether, and to what extent, MIDAS is a valid and reliable measurement to the patients suffering from myocardial infarction for the first time in Turkey. METHODS: The research was conducted with the patients hospitalized and treated with myocardial infarction in the cardiology departments of 2 hospitals in Istanbul, Turkey, between 2007 and 2008. Psychometric evaluations of TR-MIDAS were used for validity studies; language validity, content validity, construct validity were examined. For reliability studies; the tool's internal consistency reliability, Cronbach's alpha reliability coefficient, and test-retest reliability were completed. RESULTS: The instrument's content validity index was determined to be "0.95". Principal component analysis revealed six factors with an eigenvalue >1.5. Cronbach's alpha was found to be 0.89 for total scale which was an acceptable value. The total's test-retest reliability was 0.51 (p<0.01). CONCLUSION: Data obtained at the end of the study supports that Turkish Myocardial Infarction Dimensional Assessment Scale is a valid and reliable instrument as a disease-specific scale to assess the patients' quality of life suffering from myocardial infarction in Turkey. PMID- 20580317 TI - Bilateral simultaneous laparoscopic adrenalectomy for congenital adrenal hyperplasia: initial experience. AB - OBJECTIVE: Congenital adrenal hyperplasia (CAH) is an uncommon syndrome which represents a therapeutic challenge. We analyzed the role of bilateral simultaneous laparoscopic adrenalectomy in the management of CAH. MATERIAL AND METHODS: : Between October 2004 and September 2006, three female patients underwent bilateral simultaneous laparoscopic adrenalectomy for CAH. Data were retrospectively collected. Variables analyzed were persistence of CAH clinical signs, variations in 17 OH progesterone level and corticoid medication, operative time, median blood loss, postoperative pain, hospital stay, and body image perception after surgery. RESULTS: Median age was 16.3 years. Complete regression of virilization signs, acne and hyperpigmentation was achieved in one case. The other two cases showed partial regression of signs. Levels of 17 OH progesterone reached normal parameters in all cases. Steroids doses were lowered and given only for replacement purposes. Mean operative time was 125, 65 and 60min for whole, right and left procedure, respectively. Median blood loss remained under 50ml in all cases and there were no complications. Median postoperative pain level was 5 according to visual analog pain scale. Median hospital stay was 4 days. CONCLUSION: Bilateral simultaneous laparoscopic adrenalectomy shows all the advantages of minimally invasive surgery, and appears a viable alternative to medical management, which is not exempt from complications. PMID- 20580318 TI - Analyses of T cell phenotype and function reveal an altered T cell homeostasis in systemic sclerosis. Correlations with disease severity and phenotypes. AB - We investigated in systemic sclerosis (SSc) patients the T cell homeostasis and its relationship with the clinical course of the disease. Distribution of peripheral T cell subsets, thymic output, lymphocyte proliferation and apoptosis were analyzed by flow cytometry or ELISA. Age inappropriate levels of naive CD4(+) T cells and thymic output were observed. Proliferation of CD4(+) T cells, lymphocyte apoptosis and CD4(+) regulatory T (Treg) cell frequency were significantly higher than those observed in controls and significantly correlated with clinical phenotypes and clinical progression parameters i.e., diffusing capacity of the lung for carbon monoxide (DLCO) and disease activity. These data indicate that the evaluation of the T cell homeostasis can represent a valuable prognostic tool for SSc patients and it is useful to distinguish between limited and diffuse phenotypes. A therapeutic intervention targeted at reversing T cell homeostasis abnormalities would therefore potentially be helpful in counteracting disease progression. PMID- 20580319 TI - Cortical and subcortical contributions to absence seizure onset examined with EEG/fMRI. AB - In patients with idiopathic generalized epilepsies (IGEs), bursts of generalized spike and wave discharges (GSWDs) lasting > or =2 seconds are considered absence seizures. The location of the absence seizures generators in IGEs is thought to involve interplay between various components of thalamocortical circuits; we have recently postulated that medication resistance may, in part, be related to the location of the GSWD generators [Szaflarski JP, Lindsell CJ, Zakaria T, Banks C, Privitera MD. Epilepsy Behav. 2010;17:525-30]. In the present study we hypothesized that patients with medication-refractory IGE (R-IGE) and continued absence seizures may have GSWD generators in locations other than the thalamus, as typically seen in patients with IGE. Hence, the objective of this study was to determine the location of the GSWD generators in patients with R-IGE using EEG/fMRI. Eighty-three patients with IGE received concurrent EEG/fMRI at 4 T. Nine of them (aged 15-55) experienced absence seizures during EEG/fMRI and were included; all were diagnosed with R-IGE. Subjects participated in up to three 20 minute EEG/fMRI sessions (400 volumes, TR=3 seconds) performed at 4 T. After removal of fMRI and ballistocardiographic artifacts, 36 absence seizures were identified. Statistical parametric maps were generated for each of these sessions correlating seizures to BOLD response. Timing differences between brain regions were tested using statistical parametric maps generated by modeling seizures with onset times shifted relative to the GSWD onsets. Although thalamic BOLD responses peaked approximately 6 seconds after the onset of absence seizures, other areas including the prefrontal and dorsolateral cortices showed brief and nonsustained peaks occurring approximately 2 seconds prior to the maximum of the thalamic peak. Temporal lobe peaks occurred at the same time as the thalamic peak, with a cerebellar peak occurring approximately 1 second later. Confirmatory analysis averaging cross-correlation between cortical and thalamic regions of interest across seizures corroborated these findings. Finally, Granger causality analysis showed effective connectivity directed from frontal lobe to thalamus, supporting the notion of earlier frontal than thalamic involvement. The results of this study support our original hypothesis and indicate that in the patients with R IGE studied, absence seizures may be initiated by widespread cortical (frontal and parietal) areas and sustained in subcortical (thalamic) regions, suggesting that the examined patients have cortical onset epilepsy with propagation to thalamus. PMID- 20580321 TI - Psychosis and epilepsy in young people. AB - The aim of this study was to describe the clinical characteristics of children and young people under 19 with both epilepsy and a psychotic state (schizophrenia like psychotic episode, organic delusional disorder, or other brief psychotic episode). In total, the clinical case notes for 17 young people with these characteristics were identified retrospectively from three different sources. Compared with a group of young people with psychosis without epilepsy, children with epilepsy and psychosis more frequently had other neuropsychological problems like learning disability and autism. Both groups had a high rate of family histories of mental illness and social disability. Contrary to the findings in adults with psychosis and epilepsy, in this group of young people, psychosis was associated neither with temporal lobe epilepsy nor with mesial temporal sclerosis. The children with psychosis and epilepsy had a variety of seizure types and structural abnormalities. PMID- 20580320 TI - MELAS with recurrent complex partial seizures, nonconvulsive status epilepticus, psychosis, and behavioral disturbances: case analysis with literature review. AB - Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) is a progressive neurodegenerative disorder associated with polygenetic, maternally inherited, mitochondrial DNA mutations. MELAS has multisystem presentation including neurological, muscular, endocrine, auditory, visual, cardiac, psychiatric, renal, gastrointestinal and dermatological symptoms. Clinical course and prognosis are variable, often leading to cognitive decline, disability, and premature death. Both convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) are reported with MELAS. This report illustrates a case of MELAS with recurrent complex partial seizures, NCSE, confusion, aggressive behaviors, hallucinations, and paranoid delusions. Rapid video/EEG confirmation of diagnosis and aggressive antiepileptic drug intervention are required. Further education of medical professionals regarding this disorder, its appropriate management, and the significance of NCSE is indicated to avoid delay of treatment. PMID- 20580322 TI - Extraperitoneal laparoscopic approach for diagnosis and treatment of aortic lymph node recurrence in gynecologic malignancy. AB - OBJECTIVE: To estimate the safety and feasibility of extraperitoneal laparoscopic approach for the diagnosis and treatment of paraaortic lymph node recurrence in gynecologic cancers. MATERIAL AND METHODS: Between December 2002 and September 2009, 15 patients underwent extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected isolated lymph node recurrence in the Gynecologic Oncology Unit of Hospital Vall d'Hebron. The suspected diagnosis of recurrence was performed with computed tomography scanning, 18F-fluorodeoxyglucose positron emission tomography scanning, or magnetic resonance imaging. RESULTS: The median age of patients was 63 years (range 42-75). The median body mass index was 28.5 Kg/m(2) (range 18-38). The median operative time was 157.5 minutes (range 120 240). The median blood loss was 70 mL (range 30-150). The mean nodal yield was 7.7 +/- 5.3 (range 1-16). The median hospital stay was 2 days (range 2-13). There was 1 conversion to laparotomy. There was only 1 postoperative complication, a lymphorrhea that was resolved with drainage. Recurrence was confirmed in the pathologic study in 13 of the 15 patients. CONCLUSION: The extraperitoneal laparoscopic surgical approach is a feasible and safe procedure for the diagnosis of paraaortic lymph node recurrences of gynecologic cancers. The previous abdominal surgeries or treatment with chemotherapy or radiotherapy and high body mass index are not a problem. The low complication rate, low blood loss and low hospitalization allow a rapid recovery of the patients, which in turn, allows the rapid onset of adjuvant therapy. Complete debulking of suspicious lymphadenopathy offers an exact diagnosis of malignancy, and it may have a therapeutic benefit in the case of being positive. PMID- 20580323 TI - Gynecologic evaluation of catamenial pneumothorax associated with endometriosis. AB - STUDY OBJECTIVE: To assess the pathogenesis of catamenial pneumothorax associated with endometriosis from a gynecologic perspective. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Eleven patients with clinically suspected catamenial pneumothorax due to frequently recurrent pneumothorax who underwent thoracoscopy between September 2003 and February 2007 at our hospital. INTERVENTION: Video-assisted thoracoscopy. MEASUREMENTS AND MAIN RESULTS: Episodes of pneumothorax, coexistence of intrapelvic endometriosis, classification of intrathoracic lesions according to the appearance of pelvic endometriosis using the revised American Society of Reproductive Medicine (re-ASRM) classification, and histopathologic findings in intrathoracic specimens were assessed. A total of 38 episodes of pneumothorax, all on the right side, were documented in 11 patients with catamenial pneumothorax. Median (range) patient age at the initial pneumothorax was 42 (29-47) years. The re-ASRM score in 6 patients in whom pelvic endometriosis was directly observed at laparoscopy and laparotomy was 56 (18-96). We postoperatively reviewed videotape recordings of video-assisted thoracoscopy, and observed superficial thoracic diaphragmatic lesions classified as red (n = 5), black (n = 8), and white (n = 9) with fenestration according to the re-ASRM classifications for pelvic endometriosis. Tissue associated with endometriosis was detected at histopathologic analysis of resected diaphragmatic lesions in 9 patients. No endometriosis was identified at histopathologic analysis of visceral pleural lesions in 7 patients who underwent lung resection. CONCLUSIONS: Gynecologic evaluation of catamenial pneumothorax associated with endometriosis is crucial to clarify the unelucidated pathogenesis of the disease. PMID- 20580324 TI - Iatrogenic myomas: new class of myomas? AB - Parasitic myomas, defined as extrauterine seeding of leiomyoma, have been reported since the early 1900s. These myomas were thought to be spontaneously occuring, separate from the uterus but still hormone-dependent and can cause symptoms. What seemed to be a rare disorder developing from the natural history of pedunculated myomas has become increasingly reported over the last decade. Because it is still a rare disorder, the literature is limited to case reports. Herein, we review the literature and provide an analytic review of recent case reports, with emphasis on etiology, trends, and risk factors, to increase awareness of this problematic entity. PMID- 20580325 TI - An arcuate-ventrolateral periaqueductal gray reciprocal circuit participates in electroacupuncture cardiovascular inhibition. AB - Electroacupuncture (EA) suppresses elevated blood pressure (BP) by activating the arcuate nucleus, ventrolateral periaqueductal gray (vlPAG), and inhibiting cardiovascular sympathetic neurons in the rostral ventrolateral medulla. This study investigated the reciprocal neural circuit between arcuate and vlPAG during EA inhibition of reflex increases in blood pressure. In alpha-chloralose anesthetized cats the gallbladder or splanchnic nerve was stimulated to induce cardiovascular sympathoexcitatory reflexes. Electrophysiological recordings showed that EA facilitates the arcuate neural response to splanchnic nerve stimulation. Bilateral vlPAG microinjection of D,L-homocysteic acid (DLH) facilitated the arcuate response to splanchnic nerve stimulation, while microinjection of kainic acid blocked EA (P 5-6 acupoints on pericardial meridian, overlying the median nerves) excitation of arcuate neurons. Retrograde microsphere tracer labeling in the arcuate or vlPAG perikarya was found after respective microinjection of the tracer in the vlPAG or arcuate of rats, demonstrating reciprocal direct connections between the two nuclei. EA inhibition of reflex-induced BP elevation was blocked by injection of glutamate or cholinergic receptor antagonist, kynurenic acid or atropine, into the arcuate. Excitation of vlPAG neurons during EA was blocked by arcuate microinjection of glutamate NMDA and non-NMDA receptor antagonists, AP-5 and CNQX, or the cholinergic receptor antagonist, atropine. Microinjection of DLH or acetylcholine (ACh) into the arcuate facilitated EA excitation of vlPAG neurons. Microinjection of AP5 and CNQX, but not atropine, into the vlPAG blocked EA excitation of arcuate neurons. Thus, a reciprocal excitatory glutamatergic neural circuit between the arcuate and vlPAG contributes to long-lasting EA cardiovascular inhibition. ACh in the arcuate but not in the vlPAG participates in the reciprocal excitation. PMID- 20580326 TI - Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS. AB - In prior studies, we found that activation of cannabinoid-1 receptors in the nucleus tractus solitarii (NTS) prolonged baroreflex-induced sympathoinhibition in rats. In many regions of the central nervous system, activation of cannabinoid 1 receptors presynaptically inhibits gamma-aminobutyric acid (GABA) release, disinhibiting postsynaptic neurons. To determine if cannabinoid-1 receptor mediated presynaptic inhibition of GABA release occurs in the NTS, we recorded miniature inhibitory postsynaptic currents in anatomically identified second order baroreceptive NTS neurons in the presence of ionotropic glutamate receptor antagonists and tetrodotoxin. The cannabinoid-1 receptor agonists, WIN 55212-2 (0.3-30 MUM) and methanandamide (3 MUM) decreased the frequency of miniature inhibitory postsynaptic currents in a concentration-dependent manner, an effect that was blocked by the cannabinoid-1 receptor antagonist, N-(piperidin-1-yl)-5 (4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM 251, 5 MUM). Importantly, depolarization of second-order baroreceptive neurons decreased the frequency of miniature inhibitory postsynaptic currents; an effect which was blocked by the cannabinoid-1 receptor antagonist. The data indicate that depolarization of second-order baroreceptive NTS neurons induces endocannabinoid release from the neurons, leading to activation of presynaptic cannabinoid-1 receptors, inhibition of GABA release and subsequent enhanced baroreflex signaling in the NTS. The data suggest that endocannabinoid signaling in the NTS regulates short-term synaptic plasticity and provide a mechanism for endocannabinoid modulation of central baroreflex control. PMID- 20580327 TI - A validated stability-indicating HPLC method for the determination of PEGylated puerarin in aqueous solutions. AB - The aim of this study was to develop a validated specific stability-indicating HPLC method for the quantitative determination of PEGylated puerarin (PEG-PUE) in aqueous solutions. The method was validated by subjecting PEG-PUE to forced degradation under stress conditions of acid, alkali, water hydrolysis, and oxidation. Both PEG-PUE and puerarin (PUE) were simultaneously determined and separated on CAPCELL PAK C18 column by gradient elution with 0.2% aqueous phosphoric acid and acetonitrile as the mobile phase. The flow rate was 1.0 mL min(-1) and detection wavelength was set at 250 nm. Both calibration curves showed good linear regression (r> or =0.9998) within test ranges. The LOD and LOQ of PEG-PUE were determined to be 3 and 9 microg mL(-1) respectively. Degradation of PEG-PUE followed pseudo-first-order kinetics with t(1/2) of 59 min at pH 9.0 and 17.79 h at pH 7.4. However, at pH 5.0 and 2.0, there was no significant degradation of PEG-PUE over time. In conclusion, the method was observed to have the necessary specificity, precision, and accuracy, and to be suitable for quantity monitoring the degradation process of PEG-PUE during stability studies. The degradation studies may give insight into useful information for formulation development of PEG-PUE. PMID- 20580328 TI - Development and validation of a liquid chromatography-mass spectrometry method for the determination of verticinone in rat plasma and its application to pharmacokinetic study. AB - We have developed and validated a sensitive liquid chromatography-electrospray ionization-mass spectrometric (LC-ESI-MS) method for the quantification of verticinone, a major active constituent from Fritillaria hupehensis Hsiao et KC Hsia., in rat plasma. Verticinone and the internal standard (IS), hupehenine, were extracted from plasma samples by a simple liquid-liquid extraction with ethyl acetate after being alkalified by 1M ammonia hydroxide. Chromatographic separation was achieved on a C(18) column using a gradient elution program with methanol and water as the mobile phase. The detection was performed by selected ion monitoring (SIM) mode via positive electrospray ionization (ESI) interface. The lower limit of quantification (LLOQ) was 0.1 ng/mL. The calibration curves were linear (r(2)>0.998) over the concentration range of 0.1-200 ng/mL. Within- and between-run precision was less than 6.5% and accuracy was within +/-10.7%. The validated method was applied to the pharmacokinetic study of verticinone in rats after a single oral administration of 1 mg/kg. PMID- 20580329 TI - Different sample treatment approaches for the analysis of T-2 and HT-2 toxins from oats-based media. AB - A LC-DAD method is proposed for the determination of the T-2 and HT-2 toxins in cultures of Fusarium langsethiae in oat-based and other in vitro media. Test media consisted of freshly prepared milled oats to which T-2 and HT-2 toxin stock solutions were added. Different mixtures of extraction solvent (acetonitrile:water and methanol:water), extraction times (30', 60' or 90') and drying methods were investigated. Results showed that extraction with methanol:water (80:20, v/v) for 90 min, drying with N(2) and subsequent analysis by LC-DAD was the fastest and most user friendly method for detecting HT-2 and T 2 toxins production by F. langsethiae strains grown on oat-based media at levels of 0.459 and 0.508 mg of toxin/kg of agar, respectively. The proposed method was used to investigate toxin production of 6 F. langsethiae strains from northern Europe and provided clear chromatograms with no interfering peaks in media with and without glycerol as water activity modifier. PMID- 20580330 TI - [Parenteral nutrition at home]. PMID- 20580331 TI - Relationship between portal chronic inflammation and disease severity in paediatric non-alcoholic fatty liver disease. AB - BACKGROUND: The non-alcoholic steato-hepatitis Clinical Research Network has recently shown that portal chronic inflammation is associated with liver fibrosis in American children with non-alcoholic fatty liver disease. AIM: We tested whether the portal chronic inflammation-fibrosis association was present in a series of Italian children with non-alcoholic fatty liver disease. METHODS: We re assessed the liver biopsies of 144 consecutive Italian children with non alcoholic fatty liver disease aged 3-18 years and followed at the "Bambino Gesu" Paediatric Hospital. Non-alcoholic fatty liver disease and portal chronic inflammation were diagnosed using the non-alcoholic steato-hepatitis Clinical Research Network criteria. Anthropometry, body composition, liver enzymes, metabolic parameters and blood pressure were measured in all children. RESULTS: Two children had no portal chronic inflammation, 84 had mild and 58 more than mild portal chronic inflammation according to the non-alcoholic steato-hepatitis Clinical Research Network criteria. Children with no or mild portal chronic inflammation had the same clinical features of those with more than mild portal chronic inflammation except for insulin resistance, which was greater. There was no association between steatosis, lobular inflammation, ballooning, fibrosis and portal chronic inflammation. CONCLUSION: We were not able to confirm the existence of a clinico-pathological association between portal chronic inflammation and disease severity in a series of Italian children with non alcoholic fatty liver disease. Some clinico-pathological correlates of paediatric non-alcoholic fatty liver disease may be population-specific. PMID- 20580333 TI - [Deep venous thrombosis in a child with hypernatremia secondary to diabetes insipidus]. PMID- 20580332 TI - Cholangiocarcinoma in Italy: A national survey on clinical characteristics, diagnostic modalities and treatment. Results from the "Cholangiocarcinoma" committee of the Italian Association for the Study of Liver disease. AB - BACKGROUND: Very few studies assessed cholangiocarcinoma clinical characteristics. AIM: To evaluate the clinical characteristics of intra-hepatic (IH) and extra-hepatic (EH)-CCA. METHODS: We performed a national survey based on a questionnaire. RESULTS: 218 cholangiocarcinomas were observed (47% EH-CCA, 53% IH-CCA) with an age at the diagnosis higher for EH-CCA. Coexistence of cirrhosis or viral cirrhosis was more frequent in IH-CCA than EH-CCA. An incidental asymptomatic presentation occurred in 28% of IH-CCA vs 4% EH-CCA whilst, 74% EH CCA vs 28% IH-CCA presented with jaundice. 91% of IH-CCA presented as a single intra-hepatic mass, whilst 50% of EH-CCA was peri-hilar. In the diagnostic work up, 70% of all cholangiocarcinoma cases received at least 3 different imaging procedures. Tissue-proven diagnosis was obtained in 80% cholangiocarcinoma. Open surgery with curative intent was performed in 45% of IH-CCA and 29% EH-CCA. 18% IH-CCA vs 4% EH-CCA did not received treatment. CONCLUSIONS: In Italy IH-CCA is managed as frequently as EH-CCA. In comparison to EH-CCA, IH-CCA occurs at younger age and is more frequently associated with cirrhosis and with an incidental asymptomatic presentation. In contrast, most EH-CCAs are jaundiced at the diagnosis. Cholangiocarcinoma diagnostic management is cost- and time consuming with curative surgical treatment applicable more frequently in IH-CCA. PMID- 20580334 TI - The origin of regenerating axons after end-to-side neurorrhaphy without donor nerve injury. AB - The purpose of this study was to determine the origins of regenerated axons after end-to-side neurorrhaphy (ETSN) without donor nerve injury by comparing the time of appearance of regenerating axons for proximally coapted ETSN and distally coapted ETSN. Thirty rabbits were used in each group. In the proximal ETSN group, the ulnar nerve was transected and the distal end sutured to the median nerve 3cm above the elbow joint, whereas in the distal ETSN group, it was 3cm below the elbow joint. Coaptation was performed by wrapping the aponeurosis of nearby muscle. Observations were made weekly for 6 weeks after ETSN. Axonal regeneration was studied by morphometric analysis and immunohistochemistry. The times of appearance of regenerating axons differed in the proximal and distal ETSN groups. Axonal densities in proximal segments of donor nerves continuously increased and the axonal diameters of proximal segments of donor nerves continuously decreased with time after ETSN. Our findings suggest that regenerated axons after ETSN without donor nerve injury originate from the central nervous system rather than coaptation sites. PMID- 20580335 TI - Keratin sparing dorso-ulnar split skin grafts as a reconstruction option for hand defects. PMID- 20580336 TI - Venous drainage of delayed distally-based sural flap: evaluation by duplex scanning. PMID- 20580337 TI - Superior pedicle breast reduction for hypertrophy with massive ptosis. AB - Breast hypertrophy, combined with massive ptosis with a suprasternal notch-to nipple distance of more than 40 cm, remains an endeavour. Different refinements of the initial technique with free nipple grafts have been described to circumvent the problems of nipple underprojection, areolar hypopigmentation and loss of sensibility secondary to nipple grafting, as well as lacking breast projection due to scarce glandular tissue. Techniques relying on nipple areola complex transposition, rather than grafting, have been described with inferior, superomedial and medial pedicles. The aim of this study is to present the results obtained in a series of 10 patients suffering from bilateral breast hypertrophy with massive ptosis, which was defined as a distance >40 cm from the suprasternal notch-to the nipple. All breasts were managed with a superior pedicle and inverted T technique. The mean preoperative suprasternal notch-to-nipple distance was 44 +/- 2 cm, and the resection weight ranged from 800 to 2490 g per breast with an average of about 1450 g in this patient population presenting with overweight or obesity. With a mean nipple areola complex (NAC) lift of 20 +/- 3 cm, neither nipple nor areola necrosis was observed. One partial epidermolysis of the areola and two cases of delayed wound healing at the trifurcation point of the inverted T were conservatively managed. Only one re-operation was necessary for an important wound dehiscence of the lateral part of the horizontal scar. These results underscore the safety of the superior pedicle technique in cases of massive ptosis with transposition of the NAC of approximately 20 cm, that is, a pedicle length of about 25 cm. PMID- 20580338 TI - The arrow flap for nipple reconstruction: long term results. PMID- 20580339 TI - Comments on: "Long-term results of the ABG-1 hydroxyapatite coated total hip arthroplasty: Analysis of 111 cases with a minimum follow-up of 10 years". PMID- 20580340 TI - To carry or not to carry--is this the question? Disentangling the carry effect in multi-digit addition. AB - Recent research has suggested addition performance to be determined by both the need for a carry operation and problem size. Nevertheless, it has remained debatable, how these two factors are interrelated. In the current study, this question was pursued by orthogonally manipulating carry and problem size in two digit addition verification. As the two factors interacted reliably, our results indicate that the carry effect is moderated by number magnitude processing rather than representing a purely procedural, asemantic sequence of processing steps. Moreover, it was found that the carry effect may not be a purely categorical effect but may be driven by continuous characteristics of the sum of the unit digits as well. Since the correct result of a carry problem can only be derived by integrating and updating the magnitudes of tens and units within the place value structure of the Arabic number system, the present study provides evidence for the idea that decomposed processing of tens and units also transfers to mental arithmetic. PMID- 20580341 TI - Why salience is not enough: reflections on top-down selection in vision. PMID- 20580342 TI - Effect of clinician-applied maneuvers on brachial plexus stretch during a shoulder dystocia event: investigation using a computer simulation model. AB - OBJECTIVE: The objective of the study was to determine how standard shoulder dystocia maneuvers affect delivery force and brachial plexus stretch. STUDY DESIGN: A 3-dimensional computer model of shoulder dystocia was developed, including both a fetus and a maternal pelvis. Application of suprapubic pressure, rotation of the infant's shoulders, and delivery of the posterior arm following shoulder dystocia were each modeled, and delivery force and brachial plexus stretch were predicted. RESULTS: Compared with lithotomy alone, all maneuvers reduced both the required delivery force and brachial plexus stretch. The greatest effect was seen with delivery of the posterior arm, which showed a 71% decrease in anterior nerve stretch (3.9% vs 13.5%) and an 80% decrease in delivery force. CONCLUSION: The standard maneuvers met the objective of reducing the necessary delivery force compared with the lithotomy position alone. Brachial plexus stretch is also reduced when these maneuvers are used rather than continuing the delivery in lithotomy position. PMID- 20580343 TI - [Subaortic stenosis with muscularization of the anterior mitral valve leaflet: two cases]. AB - Subaortic stenosis was considered for a long time as a congenital anomaly, but it is considered now as an acquired form of obstacle to the left ventricle ejection. It constitutes 8 to 20% of the causes of obstacle left ventricle. Ventricular septal defect and aortic coarctation are the most frequent anomalies associated with the subaortic stenosis. The anomalies of mitral valve and especially muscularization of the anterior mitral valve leaflet remain very rare and underestimated. The diagnosis is made by the echocardiography and must be systematically looked for because its misunderstanding in preoperative can be at the origin of recurrences. We report in this work two cases of muscularization of the anterior mitral valve leaflet associated to subaortic stenosis. Through these cases and through a review of the literature, we are going to put the point on this rare anomaly. PMID- 20580344 TI - Provocation of delayed-onset muscle soreness in the human jaw-closing muscles. AB - Eccentric contractions of jaw-closing muscles are difficult to perform. This may explain why fatigue-inducing experiments performed so far suggest the jaw-closing muscles to be fatigue resistant. Aim of this study was to construct an apparatus that can impose intense eccentric contractions to the jaw-closing muscles, and to test the hypothesis that eccentric contractions can provoke symptoms of delayed onset muscle soreness (DOMS) in these muscles. The provocation apparatus consists of two tungsten arms connected by a hinge axis on one end. Participants bite with their anterior teeth on biting plates located on the other end. Each time the experimenter gradually releases the compression force of the apparatus' rubber tubings, the mouth is forced open and the jaw-closing muscles perform an eccentric contraction. Six male participants performed eccentric contractions of their jaw-closing muscles in six sets of exercises, each lasting 5 min, and with 1 min of rest in between. Each set consisted of 60 open-close movements. Before and after the exercises, and after 24 h, 48 h, and 1 week, feelings of fatigue and pain, the maximum mouth opening without pain, muscles' tenderness to palpation and the maximum voluntary bite force were recorded. After 24 h and 48 h, the levels of fatigue and pain were elevated, the maximum mouth opening without pain was smaller, and five of the participants reported tenderness to palpation. The maximum voluntary bite force was also smaller after 24h. These findings indicate that this novel apparatus is successful in inducing DOMS in the jaw-closing muscles. PMID- 20580345 TI - The effects of tooth extraction on alveolar bone biomechanics in the miniature pig, Sus scrofa. AB - OBJECTIVE: This study investigated the role of occlusion in the development of biomechanical properties of alveolar bone in the miniature pig, Sus scrofa. The hypothesis tested was that the tissues supporting an occluding tooth would show greater stiffness and less strain than that of a non-occluding tooth. DESIGN: Maxillary teeth opposing the erupting lower first molar (M(1)) were extracted on one side. Occlusion developed on the contralateral side. Serially administered fluorochrome labels tracked bone mineralisation apposition rate (MAR). A terminal experiment measured in vivo buccal alveolar bone strain on occluding and non occluding sides during mastication. Ex vivo alveolar strains during occlusal loading were subsequently measured using a materials testing machine (MTS/Sintech). Whole specimen stiffness and principal strains were calculated. RESULTS: MAR tended to be higher on the extraction side during occlusion. In vivo buccal shear strains were higher in the alveolar bone of the occluding side vs. the extraction side (mean of 471 microvarepsilon vs. 281 microvarepsilon, respectively; p=0.04); however, ex vivo shear strains showed no significant differences between sides. Stiffness differed between extraction and occlusion side specimens, significantly so in the low load range (344 vs. 668 MPa, respectively; p=0.04). CONCLUSIONS: Greater in vivo shear strains may indicate more forceful chews on the occluding side, whereas the similarity in ex vivo bone strain magnitude suggests a similarity in alveolar bone structure and occlusal load transmission regardless of occlusal status. The big overall change in specimen stiffness that was observed was likely attributable to differences in the periodontal ligament rather than alveolar bone. PMID- 20580346 TI - MP2, density functional theory, and molecular mechanical calculations of C-H...pi and hydrogen bond interactions in a cellulose-binding module-cellulose model system. AB - Exploring non-covalent interactions, such as C-H...pi stacking and classical hydrogen bonding (H-bonding), between carbohydrates and carbohydrate-binding modules (CBMs) is an important task in glycobiology. The present study focuses on intermolecular interactions, such as C-Hcdots, three dots, centeredpi (sugar aromatic stacking) and H-bonds, between methyl beta-d-glucopyranoside and l tyrosine-a proxy model system for a cellulose-CBM complex. This work has made use of various types of quantum mechanics (QM) and molecular mechanics (MM) methods to determine which is the most accurate and computationally efficient. The calculated interaction potential energies ranged between -24 and -38kJ/mol. The larger interaction energy is due to H-bonding between the phenyl hydroxyl of tyrosine and the O4 of the sugar. Density functional theory (DFT) methods, such as BHandHLYP and B3LYP, exaggerate the H-bond. Although one of the MM methods (viz. MM+) considered in this study does maintain the C-Hcdots, three dots, centeredpi stacking configuration, it underestimates the interaction energy due to the loss of the H-bond. When the O-H bond vector is in the vicinity of O4 (O Hcdots, three dots, centeredO4 approximately 2A, e.g., in the case of MP2/6 31G(d)), the torsional energy drops to a minimum. For this configuration, natural bond orbital (NBO) analysis also supports the presence of this H-bond which arises due to orbital interaction between one lone pair of the sugar O4 and the sigma *(O-H) orbital of the phenyl group of tyrosine. The stabilization energy due to orbital delocalization of the H-bonded system is approximately 13kJ/mol. This H-bond interaction plays an important role in controlling the CH/pi interaction geometry. Therefore, the C-Hcdots, three dots, centeredpi dispersive interaction is the secondary force, which supports the stabilization of the complex. The meta-hybrid DFT method, M05-2X, with the 6-311++G(d,p) basis set agrees well with the MP2 results and is less computationally expensive. However, the M05-2X method is strongly basis set dependent in describing this CH/pi interaction. Computed IR spectra with the MP2/6-31G(d) method show blue shifts for C1-H, C3-H, and C5-H stretching frequencies due to the C-Hcdots, three dots, centeredpi interaction. However, the M05-2X/6-311++G(d,p) method shows a small red shift for the C1-H stretching region and blue shifts for the C2-H and C3-H stretches. For the aromatic tyrosine C(delta1)-C(epsilon1) and C(delta2) C(epsilon2) bonds in the complex, the calculated IR spectra show red shifts of 12cm(-1) (MP2/6-31G(d)) and 5cm(-1) (M05-2X/6-311++G(d,p)). This study also reports the upfield shifts of computed (1)H NMR chemical shifts due to the C Hcdots, three dots, centeredpi interaction. PMID- 20580347 TI - Unique cleavage of 2-acetamido-2-deoxy-D-glucose from the reducing end of biantennary complex type oligosaccharides. AB - Basic treatment of a biantennary complex-type sialyloligosaccharide, as well as its asialo form, was found to lead to the specific cleavage of 2-acetamido-2 deoxy-d-glucose (GlcNAc) from the reducing end. The resultant oligosaccharides were identical to those prepared by treatment with endo-beta-glycosidase-M, which cleaves the glycosidic bond between two GlcNAc residues at the reducing end of N linked oligosaccharides. In addition, mechanistic studies suggested that an elimination reaction in the reducing-end terminal GlcNAc residue causes this specific cleavage reaction. PMID- 20580348 TI - Rapamycin in combination with donor-specific CD4+CD25+Treg cells amplified in vitro might be realize the immune tolerance in clinical organ transplantation. AB - It is an urgent need to induce and keep the donor-specific immune tolerance without affecting the function of normal immune defense and immune surveillance in clinical organ transplantation. Large number of studies showed that both the establishment of donor-recipient chimerism and the application of antibodies or drugs could obtain the donor-specific immune tolerance in animal transplantation model. However, the former as treatment of clinical practice has a poor feasibility, the latter has a very low success rate in clinical organ transplantation. There is a group of naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) that mediate immune tolerance by suppressing alloreactive T cells in vivo. These cells are unable to curb the occurrence of allograft rejection owing their low content. And donor-specific Tregs amplified in vitro alone can not induce donor-specific immune tolerance for recipient. Rapamycin (RPM) as a proliferation signal inhibitor, studies have shown it can effectively inhibit allograft rejection and maybe contribute to induction of immune tolerance. But there exist still many dose-dependent adverse reactions which could prevent the establishment of immune tolerance and reduce the life quality of recipients in the clinical application of RPM. Therefore, we speculate a small amount of RPM combined with donor-specific Tregs amplified in vitro may be not only induce the achievement of donor-specific tolerance, but also reduce or eliminate the side effects of RPM in clinical organ transplantation. PMID- 20580349 TI - [Cold or hot sitz baths in the emergency treatment of acute anal pain due to anorectal disease? Results of a randomised clinical trial]. AB - INTRODUCTION: The popular belief advocates the use of sitz (sitting) baths with cold water for the treatment of acute anal pain, but clinical practice guides recommend the use of hot water for its known effect on the at-rest anal pressure. AIM: The objective of the study was to examine the analgesic effect on the quality of life, manometer data and clinical progress, of the two temperatures in sitz baths in patients with anal pain. MATERIAL AND METHODS: A randomised clinical trial on patients with acute anal pain due to haemorrhoids or anal fissures, divided into Group 1: Sitz baths with water at a temperature of less than 15 degrees C, and Group 2: Baths with a water temperature above 30 degrees C. The analgesia was the same in both groups. An analysis was made of the pain at 7 days (visual analogue scale), quality of life (SF-36), anal at-rest pressure and disease progress. RESULTS: Of the 27 eligible patients, 24 were randomised (Group 1: n=12 y Group 2: n=12). There were no statistical differences in pain, but it remained stable in Group 1, but gradually decreased in the patients of Group 2, the difference being in the pain scores on the first day compared to the seventh in Group 2 (p=0.244). The rest of the variables were similar. CONCLUSION: There were no statistically significant differences in pain control from day 1 to day 7 in the Group with sitz baths with hot water. (ISRCTN Number: 50105150). PMID- 20580350 TI - What makes distributed practice effective? AB - The advantages provided to memory by the distribution of multiple practice or study opportunities are among the most powerful effects in memory research. In this paper, we critically review the class of theories that presume contextual or encoding variability as the sole basis for the advantages of distributed practice, and recommend an alternative approach based on the idea that some study events remind learners of other study events. Encoding variability theory encounters serious challenges in two important phenomena that we review here: superadditivity and nonmonotonicity. The bottleneck in such theories lies in the assumption that mnemonic benefits arise from the increasing independence, rather than interdependence, of study opportunities. The reminding model accounts for many basic results in the literature on distributed practice, readily handles data that are problematic for encoding variability theories, including superadditivity and nonmonotonicity, and provides a unified theoretical framework for understanding the effects of repetition and the effects of associative relationships on memory. PMID- 20580351 TI - [Echographic bedside measurement of the caval index for the non-invasive determination of lower central venous pressure]. PMID- 20580352 TI - [Obesity paradox in a cohort of 4,880 consecutive patients treated with percutaneous coronary intervention]. PMID- 20580353 TI - [Cervical pain and debility: Tuberculosis of an unusual location]. PMID- 20580354 TI - The amyloid fibrils of the constant domain of immunoglobulin light chain. AB - Light chain-associated (AL) amyloidosis is characterized by dominant fibril deposition of the variable domain (VL) of an immunoglobulin light chain, and thus its constant domain (CL) has been considered not to be amyloidogenic. We examined the in vitro fibril formation of the isolated CL in comparison with beta2 microglobulin (beta2-m), an immunoglobulin domain-like amyloidogenic protein responsible for dialysis-related amyloidosis. Two methods useful for beta2-m at neutral pH also induced amyloid fibrils of CL, which were monitored by thioflavin T binding and electron microscopy (EM). These results suggest that CL plays an important role, more than previously assumed, in the development of AL amyloidosis. PMID- 20580355 TI - A predicted S-type pyocin shows a bactericidal activity against clinical Pseudomonas aeruginosa isolates through membrane damage. AB - The nucleic acid sequence at the positions 1067817-1066321 of Pseudomonas aeruginosa PAO1 genome was predicted to encode a novel S-type pyocin, designated S5, based on the genome sequence. However, its antimicrobial spectrum, activity and mechanism have not been investigated. Herein, we report that pyocin S5 has an antimicrobial activity against seven clinical P. aeruginosa isolates (DWW3, InA, InB, In3, In4, In7, and In8). Among them, DWW3 is most sensitive with a minimum inhibitory concentration of 12.6 microg/ml and a killing percentage of 95.7 at 225 microg/ml. Further, we demonstrated that the antimicrobial mechanism of pyocin S5 is membrane damage, evidenced by the leakage of intracellular materials, the increase of membrane permeability, and cell surface disruption. PMID- 20580357 TI - Standardization of grading embryo morphology. AB - Standardization of morphologic assessment for an embryo grading system was developed and is being implemented by the Society for Assisted Reproductive Technology (SART). A recent European consensus conference of embryologists from Europe and America is working toward adopting an embryo classification system modeled similarly to that of SART that, if adopted, would produce a de facto international standard to aid cross-border collaboration. PMID- 20580356 TI - Comparative biology of telomeres: where plants stand. AB - Telomeres are essential structures at the ends of eukaryotic chromosomes. Work on their structure and function began almost 70 years ago in plants and flies, continued through the Nobel Prize winning work on yeast and ciliates, and goes on today in many model and non-model organisms. The basic molecular mechanisms of telomeres are highly conserved throughout evolution, and our current understanding of how telomeres function is a conglomeration of insights gained from many different species. This review will compare the current knowledge of telomeres in plants with other organisms, with special focus on the functional length of telomeric DNA, the search for TRF homologs, the family of POT1 proteins, and the recent discovery of members of the CST complex. PMID- 20580358 TI - Higher birth rate after recombinant hCG triggering compared with urinary-derived hCG in single-blastocyst IVF antagonist cycles: a randomized controlled trial. AB - In a prospective randomized controlled trial, 119 patients were randomized to receive either recombinant hCG (250 MUg) or urinary-derived hCG (10,000 IU) for final oocyte maturation in an antagonist protocol with a fixed dose of recombinant FSH (187.5 IU) and predefined single blastocyst transfer. The delivery rate was improved in the recombinant hCG group compared with the urinary derived hCG group (44.1 vs. 25.7, respectively); however, adequately powered randomized controlled trials are justified to ascertain whether this difference is true. PMID- 20580359 TI - Trauma systems and medical helicopters in the UK. PMID- 20580360 TI - Response to: Huber-Wagner S, et al. Response to: Stengel D, Frank M, Matthes G, et al. Primary pan-computed tomography for blunt multiple trauma: can the whole be better than its parts? [Injury 2009; 40(Suppl. 4):S36-46. Injury 2010 Mar 11 [Epub ahead of print]]. PMID- 20580361 TI - Effect of isosorbide mononitrate for cervical ripening before surgical termination of pregnancy in the first trimester. AB - OBJECTIVE: To evaluate the efficacy of isosorbide mononitrate (IMN) for cervical ripening prior to first trimester surgical termination of pregnancy. METHODS: A prospective, double-blind, randomized, placebo-controlled trial. Women scheduled for surgical termination of a nonviable fetus before 12 weeks of gestation from October 2008 to June 2009 were enrolled and randomly assigned to receive either 20 mg vaginally of IMN (n=24) or a placebo (n=24) 4 hours before suction evacuation. Cervical dilation before evacuation was assessed with 10-mm Hegar dilators followed by smaller sizes that were measured until the instrument passed freely through the internal os. Cervical dilation, adverse effects, termination complications, and patient satisfaction were the main outcomes. RESULTS: Mean cervical dilation was not significantly different between the IMN and placebo groups (6.29+/-0.99 mm vs 5.71+/-1.04 mm; P=0.05). Mean operative time did not differ between the groups (16+/-0.07 min vs 18+/-0.06 min; P=0.55), nor did patient satisfaction measured by visual analogue scale (7.04+/-1.68 vs 6.54+/ 1.22; P=0.24). CONCLUSION: IMN was comparable to placebo in terms of efficacy and patient satisfaction for cervical priming prior to first-trimester termination of pregnancy. PMID- 20580362 TI - The work of nurses in Australian general practice: A national survey. AB - BACKGROUND: Following recent reforms to Australia's health system, nurses now comprise a significant and growing sector of the Australian primary care workforce, but there is little data describing the services they provide. OBJECTIVES: This study aimed to describe the patient consultations of nurses in Australian general practice, including patient characteristics, reasons for the consultation, treatments provided and other actions taken. DESIGN: The study was a national cross-sectional survey, with each participating nurse collecting information about 50 nurse-patient encounters. SETTING: General practice settings in all regions of Australia. PARTICIPANTS: 108 nurses volunteered in response to advertisements and 104 returned completed study materials. Participants included Registered (Division 1) and Enrolled (Division 2) nurses working in a general practice setting. METHODS: Data were collected between May 2007 and May 2008 using a profile questionnaire and a series of encounter forms. Information was gathered on reasons for encounter, patient characteristics, and actions taken. Data were classified using the International Classification of Primary Care. RESULTS: The final data set included 5,253 nurse-patient encounters. 37.2% of patients (95% CI 33.3-41.2) were aged 65 and over, and 57.1% were female (95% CI 54.9-59.5). The majority of encounters (90.7%) were with existing patients of the practice (95% CI 89.1-92.7). The most common reasons for encounter were general and unspecified problems (35.4 per 100 encounters; 95% CI 31.8-39.1), followed by skin-related problems (20.0; 95% CI 17.3-22.8), and cardiovascular problems (11.0; 95% CI 8.7-13.3). Common management actions included medical examinations (20.7 per 100 encounters), immunisations (22.5), diagnostic tests (10.6), and dressings (15.8). Approximately 30% of encounters involved advice-giving. CONCLUSIONS: The findings confirm the generalist nature of the General Practice Nurse role, with a wide range of patient types and clinical conditions. There is a clear influence of current funding and organisational arrangements on work patterns, with tasks that have specific funding (including immunisations and wound care) featuring prominently in nurses' work. Whilst nurses' rates for presenting conditions were similar to doctors at a general level, specific actions taken and problems managed differed. New policy reforms in Australia are supporting greater flexibility in the General Practice Nurse role, maximising efficient use of nurses' skills in the primary health care context. PMID- 20580363 TI - 'Informed and uninformed decision making'--women's reasoning, experiences and perceptions with regard to advanced maternal age and delayed childbearing: a meta synthesis. AB - OBJECTIVES: To identify what factors affect women's decisions to delay childbearing, and to explore women's experiences and their perceptions of associated risks. DESIGN: Systematic procedures were used for search strategy, study selection, data extraction and analysis. Findings were synthesised using an approach developed from meta-ethnography. DATA SOURCES: We included qualitative papers, not confined to geographical area (1980-2009). Databases included CINAHL, MEDLINE, EMBASE, PsycInfo, ASSIA, MIDIRS, British Nursing Index and the National Research Register. We selected qualitative empirical studies exploring the views and experiences of women of advanced maternal age who were childless or primigravidae with a singleton pregnancy or primiparous. REVIEW METHODS: Twelve papers fulfilled the selection criteria and were included for synthesis. RESULTS: Women appear to face an issue of 'informed and uninformed decision making'; those who believe they are informed but may not be, those who are not informed and find out they are at risk once pregnant, and those who are well informed but choose to delay pregnancy anyway. Maternity services could provide information to enable informed choice regarding timing of childbearing. CONCLUSIONS: Health professionals need to be mindful of the fact that women delay childbearing for various reasons. A strategy of pre-conception education may be beneficial in informing childbearing decisions. Obstetricians and midwives should be sensitive to the fact that women may not be aware of all the risks associated with delayed childbearing. PMID- 20580364 TI - Rosiglitazone, thiazolidinediones and atherosclerosis. PMID- 20580365 TI - Leukotriene B4 mediates vascular smooth muscle cell migration through alphavbeta3 integrin transactivation. AB - Vascular injury leads to a local inflammatory response, characterized by endothelial damage, extracellular matrix exposition and aggregation/adhesion of platelets and circulating leukocytes. The release of inflammatory mediators amplifies the process, and can induce vascular smooth muscle cells (SMC) migration and proliferation. Released by leukocytes, leukotriene B4 (LTB4) induces reactive oxygen species production and SMC chemotaxis. This study was conducted to elucidate the molecular mechanisms involved in the effect of LTB4 on SMC migration, and a rat linage of vascular SMC (A7r5) were used throughout. The chemotactic effect of LTB4 was dependent on the concentration used, being comparable to AngII at 100 nM. Migration induced by LTB4 was inhibited in the presence of pertussis toxin, CP-105696, a BLT1 receptor antagonist, and by LY294002 or PD98059, two inhibitors of PI3K and MEK1/2, respectively. Stimulation of SMC with LTB4 triggered integrin-associated signaling pathways, inducing focal adhesion kinase (FAK) phosphorylation, mobilization of actin cytoskeleton, association of FAK to PI3K, ERK-2 phosphorylation and nuclear translocation, and also NFkappaB pathway activation. Pretreatment of SMC with a selective ligand of alphavbeta3 integrin, kistrin, inhibited LTB4-induced chemotaxis, FAK phosphorylation, FAK-PI3K association, and also inhibited ERK-2 and NFkappaB pathways activation. Taken together, the data demonstrated, for the first time, that the effect of LTB4 on SMC migration is modulated by integrin signaling activation, suggesting that these adhesion molecules might be important target for therapeutic intervention in cardiovascular diseases. PMID- 20580366 TI - Crystallization efficiencies of inorganic polyphosphate oligomers reacted with magnesium and calcium cations using anion-exchange chromatography with particulate formation-laser scattering detector. AB - A particulate formation-laser scattering detector (PFLSD) was developed and used for evaluating the crystallization efficiency of inorganic polyphosphates (PPs) that reacted with either magnesium or calcium cations. As the solutions for reactive crystallization, 0.5 M ammonium buffer (pH 9.6) containing either 0.15 M MgCl(2) or 0.15 M CaCl(2) (MAP: magnesium ammonium phosphate and HAP: hydroxyapatite solution) were used. In the case of mono- and diphosphate (P1 and P2), the significant dependences of the particulate formation efficiency on various types of both P1/P2 and MAP/HAP reaction solutions were observed with the direct sample injection mode. The PFLSD was hyphenated with the anion-exchange chromatography and the dependence of the particulate formation efficiency on the polymerization degree (n(p)) of PP oligomers, separated chromatographically, was evaluated sequentially. The significant suppression of the particulate formation for PP oligomers was clearly confirmed, i.e., the MAP and HAP reaction solutions did not produce the particulates of the PP oligomers having an n(p) value of more than 3 and 5, respectively. As the overall tendency, the particulate formation efficiency in the case of the HAP solution was superior to that in the case of the MAP solution. PMID- 20580367 TI - Portable, lightweight, low power, ion chromatographic system with open tubular capillary columns. AB - Basic operation principles of a lightweight, low power, low cost, portable ion chromatograph utilizing open tubular ion chromatography in capillary columns coated with multi-layer polymeric stationary phases are demonstrated. A minimalistic configuration of a portable IC instrument was developed that does not require any chromatographic eluent delivery system, nor sample injection device as it uses gravity-based eluent flow and hydrodynamic sample injection adopted from capillary electrophoresis. As a detection device, an inexpensive commercially available capacitance sensor is used that has been shown to be a suitable substitute for contactless conductivity detection in capillary separation systems. The built-in temperature sensor allows for baseline drift correction typically encountered in conductivity/capacitance measurements without thermostating device. The whole instrument does not require any power supply for its operation, except the detection and data acquisition part that is provided by a USB port of a Netbook computer. It is extremely lightweight, its total weight including the Netbook computer is less than 2.5kg and it can be continuously operated for more than 8h. Several parameters of the instrument, such as detection cell design, eluent delivery systems and data treatment were optimized as well as the composition of eluent for non-suppressed ion chromatographic analysis of common inorganic cations (Na(+), NH(4)(+), K(+), Cs(+), Ca(2+), Mg(2+), transition metals). Low conductivity eluents based on weakly complexing organic acids such as tartaric, oxalic or pyridine-2,6-dicarboxylic acids were used with contactless capacitance detection for simultaneous separation of mono- and divalent cations. Separation of Na(+) and NH(4)(+) cations was optimized by addition of 18-crown-6 to the eluent. The best separation of 6 metal cations commonly present in various environmental samples was accomplished in less than 30min using a 1.75mM pyridine-2,6-dicarboxylic acid and 3mM 18-crown-6 eluent with excellent repeatability (below 2%) and detection limits in the low micromolar range. The analysis of field samples is demonstrated; the concentrations of common inorganic cations in river water, mineral water and snow samples were determined. PMID- 20580368 TI - Comparison of two extraction methods for the analysis of per- and polyfluorinated chemicals in digested sewage sludge. AB - A rapid and reliable analytical method, based on ion-pair extraction, clean-up on Envicarb cartridge and detection by liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed for determination of 17 per- and polyfluorinated chemicals (PFCs) in digested sewage sludge. Envicarb cartridge and six labeled internal standards were selected for the elimination/reduction and correction of matrix effects, respectively. As a result, the matrix effect for perfluorooctane sulfonamides (FOSAs) and perfluorocarboxylic acids (PFCAs) with carbon chain length from C6 to C14 was lowered to a range of -14% to +28%. However, the matrix effect for other analytes was still great mainly due to the absence of appropriate internal standard. Mean recoveries of the target analytes based on matrix spikes, at different spike levels (10-300ng/g), ranged from 70% to 169%. Relative standard deviations (RSDs) were in the range of 2-20% at different spike levels. The limit of quantification (LOQ) ranged between 0.6 and 30ng/g. The method was successfully applied to several sewage sludge samples from wastewater treatment plants nearby Zurich, Switzerland. In addition, by comparing the accuracy and precision of ion-pair extraction method and methanol extraction method, we further demonstrated that the ion-pair extraction method can be used for the analysis of PFCs in sludge samples. To our knowledge, this is the first study to extract the PFCs in sewage sludge with ion-pair method and to find unsaturated fluorotelomer carboxylic acids (FTUCAs) in sewage sludge. PMID- 20580369 TI - Simultaneous determination of UV filters and polycyclic musks in aqueous samples by solid-phase microextraction and gas chromatography-mass spectrometry. AB - A simple, precise and accurate method for the simultaneous determination of four UV filters and five polycyclic musks (PCMs) in aqueous samples was developed by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). The operating conditions affecting the performance of SPME-GC-MS, including fiber thickness, desorption time, pH, salinity, extraction time and temperature have been carefully studied. Under optimum conditions (30 MUm PDMS fiber, 7 min desorption time, pH 7, 10% NaCl, 90 min extraction time at 24 degrees C), the correlation coefficients (r(2)) of the calibration curves of target compounds ranged from 0.9993 to 0.9999. The limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.2 to 9.6 ng L-1 and 0.7 to 32.0 ng L 1, respectively. The developed procedure was applied to the determinations of four UV filters and five PCMs in river water samples and internal standard was used for calibration to compensate the matrix effect. Good relative recoveries were obtained for spiked river water at low, medium and high levels. The proposed SPME method was compared with traditional SPE procedure and the results found in river water using both methods were in the same order of magnitude and both are quite agreeable. PMID- 20580370 TI - Probing the kinetic performance limits for ion chromatography. I. Isocratic conditions for small ions. AB - The first use of the kinetic plot method to characterise the performance of ion exchange columns for separations of small inorganic anions is reported. The influence of analyte type (mono- and divalent), particle size (5 and 9microm), temperature (30 and 60 degrees C) and maximum pressure drop upon theoretical extrapolations was investigated using data collected from anion-exchange polymeric particulate columns. The quality of extrapolations was found to depend upon the choice of analyte, but could be verified by coupling a series of columns to demonstrate some practical solutions for ion chromatography separations requiring relatively high efficiency. Separations of small anions yielding 25 40,000 theoretical plates using five serially connected columns (9microm particles) were obtained and yielded deviations of <15% from the kinetic plot predictions. While this approach for achieving high efficiencies results in a very long analysis time (t(0)=21min), separations yielding approximately 10,000 theoretical plates using two serially connected columns (t(0)<5min) were shown to be more practically useful for isocratic separations when compared to use of a single column operated at optimum linear velocity (t(0)>10min). PMID- 20580371 TI - Removal of Cu(II) ions from aqueous streams using poly(acrylic acid-co acrylamide) hydrogels. AB - The adsorption of Cu(II) ions from aqueous solutions onto poly(acrylic acid-co acrylamide) hydrogels was investigated. The hydrogels were prepared via free radical solution polymerization using Irgacure 754 as a photoinitiator and ethylene glycol dimethacrylate as a cross-linking agent. Loading of acrylamide/acrylic acid moieties on the surfaces of hydrogels and the amount of cross-linking agent were varied to determine the maximum metal uptake. Polymerization kinetics was investigated by (1)H NMR. The physicochemical properties of hydrogels were investigated by nitrogen sorption measurements, elemental analysis, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The (1)H NMR results demonstrated that the polymerization reaction was carried out almost to completion and confirmed the absence of residual monomers. Swelling results indicated that, by appropriate selection of cross-linking agent amount and monomer ratio, hydrogels can be swollen up to 70,000%. Further characterization of the hydrogels showed rapid adsorption kinetics and equilibrium Cu(II) adsorption capacities of 121 mg g(-1). Cu(II) adsorption kinetic data followed pseudo-first-order kinetics. Adsorption equilibrium data were better fitted by a Langmuir isotherm. FTIR and XPS results indicated the presence of a tetradentate copper complex on the surfaces of hydrogels. The copper uptake achieved suggests the potential use of hydrogels to extract toxic metals from industrial aqueous streams. PMID- 20580372 TI - Schizophrenic micellization of poly(ethylene oxide-b-methacrylic acid) induced by phosphate and calcium ions. AB - Two distinct types of micelle structures have been successfully obtained from poly(ethylene oxide-b-methacrylic acid) (PEO-b-PMAA) in aqueous solutions: one with a PEO-core surrounded by a PMAA corona and the other with a PMAA-core surrounded by a PEO-corona. The PEO-core micelles were obtained by decreasing the cloud point of the PEO to room temperature by adding phosphate ions PO(4)(3-), and the PMAA-core micelles were obtained by reducing the solubility of the PMAA block by adding calcium ions (Ca(2+)). The reversibility between the PMAA-core and PEO-core micelles was also confirmed; (1) the transformation from the PMAA core to PEO-core micelles was achieved by solubilizing the PMAA block by removing Ca(2+) with ethylenediaminetetraacetic acid followed by the addition of PO(4)(3 ), and (2) the reverse transformation was carried out by removing PO(4)(3-) by dialysis followed by the addition of Ca(2+). The two types of micelles were characterized using various techniques such as turbidimetry, dynamic light scattering, scanning electron microscopy and electrophoretic light scattering. PMID- 20580373 TI - Studies on the sorption of tetracycline onto clays and marine sediment from seawater. AB - The sorption of tetracycline onto clays and marine sediment from seawater was investigated at different pH levels, salinities (ionic strength), and temperatures. The sorption isotherms for tetracycline onto kaolinite, montmorillonite, and sediment clay were found to fit well with the Freundlich model. It is found that the linear model was better for marine sediment. Generally the sorption decreased with increasing pH and salinity. The individual sorption coefficient, Kd(n), calculated from an empirical model, showed that the sorption coefficient of positive species, Kd(+), was higher than that of zwitterions, Kd(0), and negative species, Kd(-), for montmorillonite, sediment clay, and marine sediment. The sorption capacity of marine sediment was lower than that of sediment clay due to the organic matter covered on the sorption sites. The results of the thermodynamic function calculation showed that the sorption was a spontaneous and exothermic process which was accompanied with a decrease in the degree of freedom. PMID- 20580374 TI - Limiting electrophoretic mobility of a highly charged soft particle in an electrolyte solution: solidification effect. AB - It is known that the electrophoretic mobility of a spherical rigid particle in an electrolyte solution with large kappaa (where kappa=Debye-Huckel parameter and a=particle radius) and large Dukhin number (Du>>1) tends to a nonzero constant value in the limit of high zeta potentials. A highly charged liquid drop exhibits the same limiting mobility value. That is, a liquid drop behaves as if it were a rigid particle (the solidification effect). In the present paper we derive the corresponding mobility expression for a highly charged spherical soft particle (i.e., a polyelectrolyte-coated particle) consisting of the particle core of radius a covered with an ion-penetrable surface layer of thickness d in a symmetrical electrolyte solution of valence z. It is shown that for kappaa>> and kappad>>1, the magnitude of the scaled limiting mobility mu((infinity)) is given by |mu((infinity))|=2epsilon(r)epsilon(o)kT/3etaze x (1+a(3)/2b(3)) x 2 ln 2, where epsilon(r) is the relative permittivity of the electrolyte solution, epsilon(o) is the permittivity of a vacuum, e is the elementary electric charge, and kT is the thermal energy. When a approximately b, the obtained limiting mobility expression tends to the result for a rigid sphere. That is, the solidification effect is observed also for a soft particle. PMID- 20580375 TI - Adsorption of the complex ion Au(CN)2- onto sulfur-impregnated activated carbon in aqueous solutions. AB - The adsorption of the gold-cyanide complex ion (Au(CN)(2)(-)) on sulfur impregnated activated carbon in aqueous solution has been studied in order to find a better adsorbent for the gold cyanidation process for extracting gold from ores. This study was performed using sulfur-impregnated activated carbon (SIAC 8.0) made from high-sulfur petroleum coke and an artificial aqueous solution of Au(CN)(2)(-). The experimental results have shown that Au(CN)(2)(-) strongly adsorbed onto the SIAC 8.0, leading the gold adsorption capacity of the SIAC 8.0 to be 2.25x that on conventional activated carbon. It has been also found that the adsorption fit the Langmuir isotherm well, and the adsorption density of Au(CN)(2)(-) on the SIAC 8.0 in aqueous solution increased with increasing temperature, suggesting chemical adsorption. The chemical adsorption might be attributed to the formation of S-Au-CN on SIAC 8.0 surfaces through the covalent bond between the gold atom of the ion and the sulfur in the molecular structure of the SIAC 8.0. In addition, the desorption test has demonstrated that the majority of the adsorption was irreversible, which depended on the density of the adsorption sites on the SIAC. PMID- 20580376 TI - Synthesis of mesoporous silica by a surface charge reversal route. AB - Pore size adjustable mesoporous silica was synthesized by adsorption of varying amounts of sodium dodecyl benzenesulfonate at the surface of silica activated by zinc ion via a novel surface charge reversal route. The pore size and volume can be adjusted from 5.9 to 13.76 nm and 0.88 to 1.08 cm(3) g(-1), respectively, with increasing the SDBS concentration from 0.77 to 3.08 mmol L(-1). Adsorption of Zn(2+) as a function of pH and N(2) adsorption/desorption isotherms demonstrated that the metal ions such as Zn(2+) could be readily removed with dilute nitric acid without apparent collapse of the pore structure at the proper range of SDBS concentration. PMID- 20580377 TI - Rapid synthesis of a versatile organic/inorganic hybrid material based on pyrogenic silica. AB - An efficient approach has been developed to synthesize a new versatile organo silica material by non-conventional method (microwave irradiation and ultrasonic vibration) from amorphous pyrogenic silica and has been compared with thermic procedure. The samples were fully characterized by FTIR, solid-state (29)Si and (13)C CP/MAS NMR, thermogravimetric analysis (TGA), elemental analysis, scanning electron microscopy (SEM) and by N(2)-sorption isotherms measurements. The functionalization of silicon dioxide by 4-(chloromethylphenyl) trichlorosilane has been easily achieved by ultrasound irradiation in a very short time with high loading of organic fragments. Significant different sizes of pores were observed according to conventional or non-conventional synthesis procedure. In addition, new structural properties have been created with the emergence of a mesoporosity. PMID- 20580378 TI - Improved photoluminescence properties of a novel europium(III) complex covalently grafted to organically modified silicates. AB - A series of novel organic-inorganic hybrid materials with a Eu(III) complex [(C(2)H(5))(4)N][Eu(DBM)(3)(DBM-OH)] (DBM=dibenzoylmethanate, DBM-OH=p hydroxydibenzoylmethanate) covalently bonded into vinyl-modified silica networks have been successfully assembled through a sol-gel process. DBM-OH was grafted to the coupling agent 3-(triethoxysilyl)propylisocyanate (TESPIC), and the as obtained molecular precursor DBM-Si was used as a bridge molecule both coordinate to Eu(3+) and forming an inorganic Si-O network with tetraethoxysilane (TEOS) and vinyltriethoxysilane (VTES) after cohydrolysis and co-condensation processes. The luminescence properties of VTES/TEOS composite hybrid materials were systematically studied in comparison to those of TEOS-derived hybrid material and pure [(C(2)H(5))(4)N][Eu(DBM)(4)], respectively. The results indicate that the luminescent quantum efficiencies of VTES/TEOS composite hybrid materials are greatly improved. And it is interesting to find that the luminescent intensity of VTES/TEOS composite hybrid material is enhanced by optimizing the molar ratio of VTES to TEOS (VTES:TEOS=4:6) by 3.3 and 2.4 times compared with TEOS-derived hybrid material and pure [(C(2)H(5))(4)N][Eu(DBM)(4)], respectively. In addition, the thermal stability of the emission was also improved considerably. The results presented in this paper indicate that the use of vinyl-modified silicates as a matrix opens the door to improving the photoluminescence properties of Eu(III) complexes. PMID- 20580379 TI - The cognitive profile of Chinese children with mathematics difficulties. AB - This study examined how four domain-specific skills (arithmetic procedural skills, number fact retrieval, place value concept, and number sense) and two domain-general processing skills (working memory and processing speed) may account for Chinese children's mathematics learning difficulties. Children with mathematics difficulties (MD) of two age groups (7-8 and 9-11 years) were compared with age-matched typically achieving children. For both age groups, children with MD performed significantly worse than their age-matched controls on all of the domain-specific and domain-general measures. Further analyses revealed that the MD children with literacy difficulties (MD/RD group) performed the worst on all of the measures, whereas the MD-only group was significantly outperformed by the controls on the four domain-specific measures and verbal working memory. Stepwise discriminant analyses showed that both number fact retrieval and place value concept were significant factors differentiating the MD and non-MD children. To conclude, deficits in domain-specific skills, especially those of number fact retrieval and place value understanding, characterize the profile of Chinese children with MD. PMID- 20580380 TI - Maintenance of anti-inflammatory cytokines and reduction of glial activation in the ischemic hippocampal CA1 region preconditioned with lipopolysaccharide. AB - Lipopolysaccharide (LPS) induces a strong immune response, and pretreatment with low dose of LPS suppresses the production of proinflammatory mediators. In the present study, we investigated the effect of LPS preconditioning on the delayed neuronal death in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia. LPS preconditioning showed neuroprotective effects against ischemic damage in the hippocampal CA1 region after ischemic insult: about 92% of neurons in the CA1 region survived in the LPS-treated ischemia group. LPS preconditioning maintained anti-inflammatory cytokines, such as interleukin (IL) 4 and IL-13, in pyramidal neurons in the CA1 region after ischemia/reperfusion. In addition, IL-4 and IL-13 protein levels in the CA1 region of the LPS-treated ischemia group were similar to the vehicle-treated sham group. We found that reactive gliosis was markedly attenuated in the CA1 region of the LPS-treated ischemia group compared to the vehicle-treated ischemia group using immunohistochemistry of glial fibrillary acidic protein for astrocytes, and ionized calcium-binding adapter molecule 1 and isolectin B4 for microglia. These results indicate that LPS preconditioning may provide neuroprotection in the ischemic hippocampal CA1 region via maintenance of anti-inflammatory cytokines and suppression of glial activation. PMID- 20580381 TI - Coral Ba/Ca records of sediment input to the fringing reef of the southshore of Moloka'i, Hawai'i over the last several decades. AB - The fringing reef of southern Moloka'i is perceived to be in decline because of land-based pollution. In the absence of historical records of sediment pollution, ratios of coral Ba/Ca were used to test the hypothesis that sedimentation has increased over time. Baseline Ba/Ca ratios co-vary with the abundance of red, terrigenous sediment visible in recent imagery. The highest values at One Ali'i are near one of the muddiest parts of the reef. This co-varies with the lowest growth rate of all the sites, perhaps because the upstream Kawela watershed was historically leveed all the way to the nearshore, providing a fast-path for sediment delivery. Sites adjacent to small, steep watersheds have ~decadal periodicities whereas sites adjacent to mangrove forests have shorter-period fluctuations that correspond to the periodicity of sediment transport in the nearshore, rather than the watershed. All four sites show a statistically significant upward trend in Ba/Ca. PMID- 20580382 TI - [Deforming gout]. PMID- 20580383 TI - The patterns of glucose tolerance and insulin resistance among rural Chinese twin children, adolescents, and young adults. AB - Pubertal insulin resistance (IR) is well recognized; but little data are available for glucose and insulin pattern from a large, unselected lean population. This report describes the age- and sex-specific distributions of glucose tolerance and IR in a rural Chinese twin population. This report includes 4488 subjects aged 6 to 24 years. The primary variables of interest are fasting plasma glucose, 2-hour postload plasma glucose (2-h PG), fasting serum insulin, 2 hour postload insulin, and the homeostatic model assessment for IR. Age- and sex specific patterns for the primary variables are described using smoothing plot, arithmetic or geometric mean, and percentiles. There is an increase in fasting plasma glucose, 2-h PG, and IR during puberty (10-19 years) and a return to prepuberty level by the age of 20 years. Insulin resistance peaks at around the age of 14 years in girls and 16 years in boys. Two-hour postload plasma glucose and 2-hour postload insulin are higher in girls than in boys from early puberty, and the sex differences are more pronounced afterward. Moreover, the prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) increases after puberty and is higher in girls than in boys. In this community-based, nonobese rural Chinese twin population, we observed sex-specific remarkable pubertal surge of IR and modest increase in plasma glucose as well as increasing prevalence of IFG and IGT with age. Notably, females had higher 2-h PG and higher prevalence of IFG and IGT. Our study underscored that adolescence (even more so in females) is a critical period for developing IR and prediabetes. PMID- 20580384 TI - The role of JAZF1 on lipid metabolism and related genes in vitro. AB - JAZF1 is a novel gene that is associated with diabetes mellitus and prostate cancer according to genomewide association studies; however, little is known about the function of this gene in regulating metabolism. In the present study, we have shown the expression of JAZF1 in various mouse tissues. To elucidate its role in metabolism, we investigated the influence of an overexpression of JAZF1 on 3T3-L1 adipose cells and hepatoma carcinoma Hepa1-6 cells that represent target tissues for diabetes and insulin resistance. In both cells, JAZF1 overexpression led to a substantial reduction in the expression of acetyl coenzyme A carboxylase, fatty acid synthetase, and sterol regulatory element binding protein 1 messenger RNA (mRNA). The level of hormone-sensitive lipase mRNA significantly increased. The expression of JAZF1 in 3T3-L1 adipocyte exhibited suppressive effects on lipid accumulation and decreased droplet size. In addition, the transcription for glucose transport 1 was significantly higher than the control in the Hepa1-6 cell line; but it was not significantly different in 3T3-L1. These results showed that JAZF1 in adipocytes and liver cells reduces lipid synthesis and increases lipolysis mainly by down-regulating the levels of sterol regulatory element-binding protein 1, acetyl-coenzyme A carboxylase, and fatty acid synthetase mRNA expression and by increasing hormone-sensitive lipase mRNA expression. Because it had an effect on the decrease of the maturation of lipid droplets and fat storage, we speculate that JAZF1 might represent a potential target against diabetes and obesity. PMID- 20580385 TI - Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation. AB - The Fenofibrate Intervention and Event Lowering in Diabetes study demonstrated that treatment with fenofibrate in individuals with type 2 diabetes mellitus not only reduced nonfatal coronary events but also diminished the need for laser treatment of diabetic retinopathy and delayed the progression of diabetic nephropathy. However, the mechanism by which fenofibrate may have altered the microvasculature remains unclear. We thus investigated the effect of fenofibrate on human glomerular microvascular endothelial cells (HGMEC). Treatment of HGMEC with fenofibrate resulted in transient activation of adenosine monophosphate activated protein kinase (AMPK), thereby inducing the phosphorylation of Akt and endothelial nitric oxide synthase, leading to nitric oxide production. We compared AMPK activation induced by bezafibrate and WY14643 with that induced by fenofibrate in HGMEC as well as HepG2 cells. Only fenofibrate activated AMPK in HGMEC. Fenofibrate also inhibited nuclear factor-kappaB activation by advanced glycation end-products, thereby suppressing the expression of various adhesion molecule genes in HGMEC. Suppression of fenofibrate-induced inhibition of nuclear factor-kappaB activation was observed in cells treated with AMPK small interfering RNA or compound C. Furthermore, fenofibrate was observed to significantly suppress apoptosis of HGMEC in hyperglycemic culture medium. Treatment with compound C or Nw-nitro-L-arginine methyl ester (L-NAME) abolished the suppressive effect of fenofibrate on HGMEC apoptosis. Our findings suggest that fenofibrate might exert a protective effect on the microvasculature by suppressing inflammation and apoptosis through AMPK activation beyond its lipid lowering actions. PMID- 20580386 TI - Characterization of a Vitis vinifera cv. Cabernet Sauvignon 3',5'-O methyltransferase showing strong preference for anthocyanins and glycosylated flavonols. AB - At ripening initiation in red grapevine (Vitis vinifera) berries, the exocarp turns color from green to red and then to purple due to the accumulation and extent of methylation of anthocyanins. The accumulation of transcripts encoding an O-methyltransferase was recently shown to be closely correlated with the onset of ripening and the degree of blue/purple pigmentation in grapevine berries; however, the biochemical function of this gene has remained uncharacterized. In this study, an O-methyltransferase cDNA that showed a distinct expression pattern when compared to closely related sequences was expressed in Escherichia coli and enzyme assays were carried out with a broad array of anthocyanin and other flavonoid substrates. We demonstrate that this enzyme carries out 3',5'-O methylation of anthocyanins and flavonol compounds in vitro, which are known to be present in grape berries, with a preference for glycosylated substrates. The highest relative specific activity for the enzyme was found with delphinidin 3-O glucoside as substrate. The enzyme is not able to methylate flavan type skeletons with chiral centers, such as either catechins or dihydroquercetin. The enzyme showed negligible specific activity for caffeoyl-CoA, compared to flavonol and anthocyanin substrates. Phylogenetic analysis of the O-methyltransferase suggests that it may be a member of a distinct subclass of Type 2 bivalent metal-dependent S-adenosyl-methionine O-methyltransferases. PMID- 20580387 TI - Recombinant mid gut antigen (Bm95) as a vaccine against Indian Rhiphicephalus haemaphysaloides in Bos indicus cattle. AB - In the present study, we report for the first time the efficacy of recombinant Bm95 mid gut antigen isolated from an Argentinean strain of Rhipicephalus microplus strain A in controlling the tick infestations in India. The synthetic gene for Bm95 optimized for expression in yeast was obtained and used to generate yeast transformants expressing Bm95 which was purified to apparent homogeneity. Liquid chromatography-mass spectrometry analysis of the purified protein confirmed its identity as Bm95. Vaccine was prepared by blending various concentrations of purified Bm95 with aluminium hydroxide as an adjuvant. Immunogenicity studies of the vaccine in rabbits and cattle indicated that the vaccine was highly immunogenic. The efficacy studies of the vaccine was done in cattle. Naive Bos indicus cattle were vaccinated with the recombinant vaccine and were challenged with the larval, nymphal and adult forms of Rhiphicephalus haemaphysaloides. The vaccine protected the animals from larval, nymph and adult tick challenges with an efficacy of 98.7%, 84.6% and 78.9% respectively. The results obtained from the above studies clearly demonstrated the advantage and possibilities of the use of Bm95 in controlling R. haemaphysaloides infestations in the field. PMID- 20580388 TI - Natural frequency of polymorphisms linked to the chondroitin 4-sulfotransferase genes and its association with placental malaria. AB - Our understanding about the role of the maternal genetic factors on placental malaria is scarce. The general aim of this work was to examine whether common polymorphisms of genes involved in chondroitin sulphate A (CSA) synthesis influence susceptibility to and manifestation of malaria during pregnancy. To achieve this, 96 women with placental malaria and 180 healthy controls without malaria from the province of Luanda, Angola, were genotyped using six microsatellite loci. No associations were found between polymorphisms of genes involved in CSA synthesis and placental malaria. All these findings suggest that there is no genetic susceptibility or increased risk attributed to polymorphisms of the enzymes involved on the synthesis of CSA. PMID- 20580389 TI - Investigation of Lamb elastic waves in anisotropic multilayered composites applying the Green's matrix. AB - This article presents a numerical study of dispersion characteristics of some symmetric and antisymmetric composites modelled as multilayered packets of layers with arbitrary anisotropy of each layer. The authors introduce a subsidiary boundary problem of three-dimensional elasticity theory for the system of partial differential equations describing the harmonic oscillations of the composite caused by a surface load. The problem reduces to a boundary problem for ordinary differential equations by employing the Fourier transform. An algorithm of constructing the Fourier transform of the Green's matrix of the given boundary problem is presented. The wave numbers of Lamb waves propagating in composites, their phase velocity surfaces and group wave surfaces are presented through the poles of the transform of the Green's matrix. The authors obtain the dispersion curves for different directions and frequencies and investigate the dispersion curves and surfaces of wave numbers, phase velocities and group wave surfaces for various composites. The numerical results are then compared with the results obtained by applying other methods. PMID- 20580390 TI - Persistence of viral infection despite similar killing efficacy of antiviral CD8(+) T cells during acute and chronic phases of infection. AB - Why some viruses establish chronic infections while others do not is poorly understood. One possibility is that the host's immune response is impaired during chronic infections and is unable to clear the virus from the host. In this report, we use a recently proposed framework to estimate the per capita killing efficacy of CD8(+) T cells, specific for the polyoma virus (PyV), which establishes a chronic infection in mice. Surprisingly, the estimated per cell killing efficacy of PyV-specific effector CD8(+) T cells during the acute phase of the infection was very similar to the efficacy of effector CD8(+) T cells specific to lymphocytic choriomeningitis virus (LCMV-Armstrong), which is cleared from the host. Our results suggest that persistence of PyV does not result from the generation of an inefficient PyV-specific CD8(+) T cell response, and that other host or viral factors are responsible for the ability of PyV to establish chronic infection. PMID- 20580391 TI - Complete genome sequence analysis of candidate human rotavirus vaccine strains RV3 and 116E. AB - Rotaviruses (RVs) cause severe gastroenteritis in infants and young children; yet, several strains have been isolated from newborns showing no signs of clinical illness. Two of these neonatal strains, RV3 (G3P[6]) and 116E (G9P[11]), are currently being developed as live-attenuated vaccines. In this study, we sequenced the eleven-segmented double-stranded RNA genomes of cell culture adapted RV3 and 116E and compared their genes and protein products to those of other RVs. Using amino acid alignments and structural predictions, we identified residues of RV3 or 116E that may contribute to attenuation or influence vaccine efficacy. We also discovered residues of the VP4 attachment protein that correlate with the capacity of some P[6] strains, including RV3, to infect newborns versus older infants. The results of this study enhance our understanding of the molecular determinants of RV3 and 116E attenuation and are expected to aid in the ongoing development of these vaccine candidates. PMID- 20580394 TI - Domain disruptions of individual 3B proteins of foot-and-mouth disease virus do not alter growth in cell culture or virulence in cattle. AB - Picornavirus RNA replication is initiated by a small viral protein primer, 3B (also known as VPg), that is covalently linked to the 5' terminus of the viral genome. In contrast to other picornaviruses that encode a single copy of 3B, foot and-mouth disease virus (FMDV) encodes three copies of 3B. Viruses containing disrupted native sequence or deletion of one of their three 3B proteins were derived from a FMDV A24 Cruzeiro full-length cDNA infectious clone. Mutant viruses had growth characteristics similar to the parental virus in cells. RNA synthesis and protein cleavage processes were not significantly affected in these mutant viruses. Cattle infected by aerosol exposure with mutant viruses developed clinical disease similar to that caused by the parental A24 Cruzeiro. Therefore, severe domain disruption or deletion of individual 3B proteins in FMDV do not affect the virus' ability to replicate in vitro and cause clinical disease in cattle. PMID- 20580393 TI - Design and evaluation of antiretroviral peptides corresponding to the C-terminal heptad repeat region (C-HR) of human immunodeficiency virus type 1 envelope glycoprotein gp41. AB - Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants. PMID- 20580392 TI - Protective immunity against H5N1 influenza virus by a single dose vaccination with virus-like particles. AB - We generated influenza virus-like particles (VLPs) containing the wild type (WT) H5 hemagglutinin (HA) from A/Viet Nam/1203/04 virus or a mutant H5 HA with a deletion of the multibasic cleavage motif. VLPs containing mutant H5 HA were found to be as immunogenic as VLPs containing WT HA. A single intramuscular vaccination with either type of H5 VLPs provided complete protection against lethal challenge. In contrast, the recombinant H5 HA vaccine was less immunogenic and vaccination even with a 5 fold higher dose did not induce protective immunity. VLP vaccines were superior to the recombinant HA in inducing T helper type 1 immune responses, hemagglutination inhibition titers, and antibody secreting cells, which significantly contribute to inducing protective immunity after a single dose vaccination. This study provides insights into the potential mechanisms of improved immunogenicity by H5 VLP vaccines as an approach to improve the protective efficacy against potential pandemic viruses. PMID- 20580395 TI - Multiple pathways to the attenuation of West Nile virus in south-east Texas in 2003. AB - West Nile virus (WNV) was first detected in Texas in 2002. During 2003, several isolates exhibiting significant attenuation of mouse neuroinvasiveness, and in some cases a small plaque and temperature sensitive phenotype when compared to other North American WNV isolates, were obtained from birds and mosquitoes in South-East Texas. To determine the attenuation markers of WNV, we have sequenced the genomes of three attenuated isolates and four temporally related virulent isolates and compared the amino acid substitutions in a total of 101 isolates, including three previously published genomes of attenuated strains, to identify mutations that are potentially involved in attenuation. Surprisingly, the attenuated strains fall into three separate "groups", suggesting that the attenuated phenotype evolved on three separate occasions in 2003. None of the groups share the same nucleotide changes or amino acid substitutions, and there are few mutations that can be clearly defined alone as being associated with attenuation. PMID- 20580396 TI - Dogs are highly susceptible to H5N1 avian influenza virus. AB - Replication of avian influenza viruses (AIVs) in dogs may facilitate their adaptation in humans; however, the data to date on H5N1 influenza virus infection in dogs are conflicting. To elucidate the susceptibility of dogs to this pathogen, we infected two groups of 6 beagles with 10(6) 50% egg-infectious dose of H5N1 AIV A/bar-headed goose/Qinghai/3/05 (BHG/QH/3/05) intranasally (i.n.) and intratracheally (i.t.), respectively. The dogs showed disease symptoms, including anorexia, fever, conjunctivitis, labored breathing and cough, and one i.t. inoculated animal died on day 4 post-infection. Virus shedding was detected from all 6 animals inoculated i.n. and one inoculated i.t. Virus replication was detected in all animals that were euthanized on day 3 or day 5 post-infection and in the animal that died on day 4 post-infection. Our results demonstrate that dogs are highly susceptible to H5N1 AIV and may serve as an intermediate host to transfer this virus to humans. PMID- 20580398 TI - Geochemical changes in individual sediment grains during sequential arsenic extractions. AB - High concentrations of As in groundwater frequently occur throughout the world. The dissolved concentration, however, is not necessarily determined by the amount of As in the ambient sediment but rather by the partitioning of As between different minerals and the type of fixation. Sequential extractions are commonly applied to determine associations and binding forms of As in sediments. Due to the operational nature of the extracted fractions, however, the results do not provide insight into how and where precisely As is bound within mineral grains and no information about elemental associations or involved mineral phases can be gained. Furthermore, little is known about possible geochemical alterations that actually occur within a single grain during sequential extraction. Therefore, micro-synchrotron X-ray fluorescence analysis was applied to study the micro scale distribution of As and other elements in single sediment grains. Arsenic was found to be mainly enriched in Fe oxy-hydroxide coatings along with other heavy metals resulting in high correlations. Phosphate leached 34-66% of As from the studied grains. The release of As in this leaching step was accompanied by the disappearance of correlations between As and Fe as well as by a higher Fe/As ratio compared to untreated samples. During the Fe-leaching step the coatings were largely dissolved leading to much lower concentrations of As and Fe. The correlation between As and Fe was preserved only in association with K, indicating the presence of both elements in silicate structures. Several distinctive features were observed such as the release of Fe, Mn and Cr during phosphate leaching as well as the lowering of mean K concentrations due to the Fe leaching which indicates that not only target mineral phases were dissolved in these extraction steps. The importance of re-precipitation processes during sequential extraction was indicated by a consistently observed increase of the Fe/As ratio from the untreated to the Fe-leached samples. PMID- 20580397 TI - Virion incorporation of the herpes simplex virus type 1 tegument protein VP22 is facilitated by trans-Golgi network localization and is independent of interaction with glycoprotein E. AB - HSV-1 virions contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The molecular mechanisms that facilitate incorporation of tegument proteins are poorly characterized. The tegument protein VP22 interacts with VP16 and the cytoplasmic tail of glycoprotein E (gE). Virion incorporation of VP22 occurs independently of interaction with VP16; however, the contribution of gE binding remains undefined. Site-directed mutagenesis was used to identify VP22 mutants which abrogate interaction with gE but retain VP16 binding. Virion incorporation assays demonstrated that failure to bind gE did not abrogate VP22 packaging. A region of VP22 which binds to both VP16 and gE failed to be packaged efficiently, with wild-type levels of incorporation only attained when residues 43-86 of VP22 were present. Mutational analysis of an acidic cluster of amino acids within this region indicates that this motif facilitates trans-Golgi network (TGN) localization and optimal virion incorporation of VP22. PMID- 20580399 TI - Formation of methyl iodide on a natural manganese oxide. AB - This paper demonstrates that manganese oxides can initiate the formation of methyl iodide, a volatile compound that participates to the input of iodine into the atmosphere. The formation of methyl iodide was investigated using a natural manganese oxide in batch experiments for different conditions and concentrations of iodide, natural organic matter (NOM) and manganese oxide. Methyl iodide was formed at concentrations 80MUg/L at a site on Crosswicks Creek) with arsenite generally the dominant species. Low dissolved oxygen, low or undetectable levels of nitrate and sulfate, detectable sulfide concentrations, and high concentrations of iron and dissolved organic carbon (DOC) in the groundwater indicate that reducing environments are present beneath the streambeds and that microbial activity, fueled by the DOC, is involved in releasing arsenic and iron from the geologic materials. In groundwater with the highest arsenic concentrations at Crosswicks Creek, arsenic respiratory reductase gene (arrA) indicated the presence of arsenic-reducing microbes. From extracted DNA, 16s rRNA gene sequences indicate the microbial community may include arsenic-reducing bacteria that have not yet been described. Once in the stream, iron is oxidized and precipitates as hydroxide coatings on the sediments. Arsenite also is oxidized and co-precipitates with or is sorbed to the iron hydroxides. Consequently, dissolved arsenic concentrations are lower in streamwater than in the groundwater, but the arsenic contributed by groundwater becomes part of the arsenic load in the stream when sediments are suspended during high flow. A strong positive relation between concentrations of arsenic and DOC in the groundwater samples indicates that any process-natural or anthropogenic-that increases the organic carbon concentration in the groundwater could stimulate microbial activity and thus increase the amount of arsenic that is released from the geologic materials. PMID- 20580402 TI - Development of granular sludge for textile wastewater treatment. AB - Microbial granular sludge that is capable to treat textile wastewater in a single reactor under intermittent anaerobic and aerobic conditions was developed in this study. The granules were cultivated using mixed sewage and textile mill sludge in combination with anaerobic granules collected from an anaerobic sludge blanket reactor as seed. The granules were developed in a single sequential batch reactor (SBR) system under alternating anaerobic and aerobic condition fed with synthetic textile wastewater. The characteristics of the microbial granular sludge were monitored throughout the study period. During this period, the average size of the granules increased from 0.02 +/- 0.01 mm to 2.3 +/- 1.0 mm and the average settling velocity increased from 9.9 +/- 0.7 m h(-1) to 80 +/- 8 m h(-1). This resulted in an increased biomass concentration (from 2.9 +/- 0.8 g L(-1) to 7.3 +/- 0.9 g L(-1)) and mean cell residence time (from 1.4 days to 8.3 days). The strength of the granules, expressed as the integrity coefficient also improved. The sequential batch reactor system demonstrated good removal of COD and ammonia of 94% and 95%, respectively, at the end of the study. However, only 62% of color removal was observed. The findings of this study show that granular sludge could be developed in a single reactor with an intermittent anaerobic-aerobic reaction phase and is capable in treating the textile wastewater. PMID- 20580403 TI - Compositional changes in the hydrophobic acids fraction of drainage water from different land management practices. AB - Dissolved organic matter (DOM) can play a key role in many environmental processes, including carbon cycling, nutrient transport and the fates of contaminants and of agrochemicals. Hydrophobic acids (Ho), the major components of the DOM, were recovered from the drainage waters from well-drained (WDS) and poorly-drained (PDS) Irish grassland soils in lysimeters, amended with N fertiliser (F) and with bovine urine (U) and were studied using 1D and 2D solution-state Nuclear Magnetic Resonance (NMR) spectroscopy. The Diffusion Edited (DE) (1)H NMR spectra indicated that the Ho consisted largely of larger molecules, or of molecules that formed rigid aggregates, and the 1D and the 2D (Heteronuclear Multiple Quantum Coherence - HMQC, the Total Correlation Spectroscopy - TOCSY, and the Nuclear Overhauser Effect - NOESY) spectra indicated that the samples were composed of lignin residues, carbohydrates, protein/peptides, and aliphatic components derived from plant waxes/cuticular materials and from microbial lipids. The F amendments increased the concentrations of Ho in the waters by 1.5 and 2.5 times those in the controls in the cases of WDS and PDS, respectively. The lignin-derived components were increased by 50% and 300% in the cases of the Ho from the WDS and PDS, respectively. Applications of F + U decreased the losses of Ho, (compared to the F amendments alone) and very significantly decreased those of the lignin-derived materials, indicating that enhanced microbial activity from U gave rise to enhanced metabolism of the Ho components, and especially of lignin. In contrast the less biodegradable aliphatic components containing cuticular materials increased as the result of applications of F + U. This study helps our understanding of how management practices influence the movement of C between terrestrial and aquatic environments. PMID- 20580404 TI - The rate of spontaneous cleavage of the glycosidic bond of adenosine. AB - Previous estimates of the rate of spontaneous cleavage of the glycosidic bond of adenosine were determined by extrapolating the rates of the acid- and base catalyzed reactions to neutral pH. Here we show that cleavage also proceeds through a pH-independent mechanism. Rate constants were determined as a function of temperature at pH 7 and a linear Arrhenius plot was constructed. Uncatalyzed cleavage occurs with a rate constant of 3.7x10(-12)s(-1) at 25 degrees C, and the rate enhancement generated by the corresponding glycoside hydrolase is approximately 5x10(12)-fold. PMID- 20580405 TI - Aza-beta(3)-amino acid containing peptidomimetics as cAMP-dependent protein kinase substrates. AB - Peptidomimetic analogs of the peptide RRASVA, known as the "minimal substrate" of the catalytic subunit of the cAMP-dependent protein kinase (PKA), were synthesized by consecutive replacement of natural amino acids by their aza beta(3) analogs. The peptidomimetics were tested as PKA substrates and the kinetic parameters of the phosphorylation reaction were determined. It was found that the interaction of these peptidomimetics with the enzyme active center was sensitive to the location of the backbone modification, while the maximal rate of the reaction was practically not affected by the structure of substrates. The pattern of molecular recognition of peptidomimetics was in agreement with the results of structure modeling and also with the results of computational docking study of peptide and peptidomimetic substrates with the active center of PKA. It was concluded that the specificity determining factors which govern substrate recognition by the enzyme should be grouped along the phosphorylatable substrate, and such clustering might open new perspectives for pharmacophore design of peptides and peptide-like ligands. PMID- 20580406 TI - Toxic effects and specific chromium acquired resistance in selected strains of Dyctiosphaerium chlorelloides. AB - Due to its various uses, chromium contamination has become widespread in a diverse array of environments. The present study was carried out to investigate the toxic effect of chromium exposures on sensitive and resistant strains of the green algae Dyctiosphaerium chlorelloides, and to determine the nature and mechanism of chromium-resistant cells that arise. The toxic effect on the photosynthetic performance of chromium exposures in both cell populations, and the sensitive differences due to chromium oxidation state, were estimated, and the results indicate that although the photosynthetic performance in both strains were inhibited, there are not significant differences among IC(50(72)) values obtained in toxicity assays with both chromium oxidation states in wild-type cells, and however these differences are very significant when the assays were performed with Cr(VI) resistant cells. The 72-h 50% inhibitory concentration values obtained with Cr(III) exposures were similar for both strains. Additionally, by means of the SEM/EDX and TEM microscopic techniques, the occurrence of rapid morphological evolution in the microalgal cells and the possible detoxificant mechanisms was observed after exposure of the wild strain to chromium hexavalent. Moreover, the different response in photosynthetic activity observed between sensitive and resistant cells of D. chlorelloides in the presence of Cr(VI) and Cr(III) could be used to obtain a chromium-specific eukaryotic microalgal biosensor. PMID- 20580407 TI - Thermally-induced transformation of hexabromocyclo dodecanes and isobutoxypenta bromocyclododecanes in flame-proofed polystyrene materials. AB - Polystyrenes (PS) are produced in quantities exceeding 10 Mt y(-1). They are used for insulation and packaging materials, often in flame-proofed forms with hexabromocyclododecanes (HBCDs) added as flame retardants. Polystyrenes are also constituents of plastic debris found in the aquatic environment. HBCDs are now considered as persistent, bioaccumulative, and toxic compounds. Lately, we reported that isobutoxypenta bromocyclododecanes (iBPBCDs), a formerly unknown class of polybrominated compounds, are also present in flame-proofed polystyrenes. It is therefore likely that iBPBCDs are released along with HBCDs from these materials. Herein, we report on changes of the HBCD- and iBPBCD patterns when exposing expanded (EPS) and extruded (XPS) polystyrenes at temperatures of 140-160 degrees C. Substantial transformation reactions were observed in EPS, which was rich in gamma-HBCDs and delta-, eta-, and theta iBPBCDs at the beginning, but changed to materials rich in alpha-HBCDs and alpha , beta-, epsilon-, and xi-iBPBCDs. Patterns of untreated XPS already resembled those of the thermally treated EPS. Upon thermal exposure, some further enrichment of alpha-HBCDs and alpha-, beta-, epsilon-, and xi-iBPBCDs was also noticed for the XPS samples, indicating similar transformation mechanisms. Comparable apparent first-order transformation rate constants (k(trans)) of 0.003, -0.008, and -0.020 min(-1) and -0.004, -0.009, and -0.019 min(-1) are found for gamma-HBCD- and delta-iBPBCD-conversion at 140, 150, and 160 degrees C, respectively. We conclude that a thermal treatment of flame-proofed polystyrenes alters their HBCD- and iBPBCD-patterns. Thus depending on the proportions of EPS and XPS materials reaching the environment, more of the lipophilic (late-eluting) or of the more polar (early-eluting) HBCD- and iBPBCD-stereoisomers will be released. Several properties such as partitioning coefficients, degradation rates, and bioaccumulation factors are stereoisomer-specific. Therefore, the environmental fate of individual HBCDs and iBPBCDs is expected to vary, the specific stereoisomer pattern in polystyrenes at a potential source is another important aspect to consider. PMID- 20580408 TI - Gene transcription and higher-level effects of multigenerational Zn exposure in Daphnia magna. AB - Zn exposure of Daphnia magna during one generation has been shown to modulate gene transcription differently in Zn exposed organisms compared to their non exposed offspring. Here we studied the transcriptional gene regulation with a cDNA microarray in D.magna exposed to Zn for three generations (F0-F2). For the first time molecular effects of multigeneration toxicant exposure in D. magna are described. Out of 73 differentially transcribed genes in the F1Zn exposed generation (compared to the F1 control), only seven genes were also differentially transcribed in the same direction in the F0Zn exposed daphnids (up or down, compared to the F0 control). The majority of the differentially transcribed unigenes in F1Zn exposed daphnids (78%) were not differentially transcribed in the F0Zn exposed organisms. This indicates that Zn exposure affected other molecular pathways in the second exposed generation, although a reduced reproduction and a reduction in juvenile growth were observed in both Zn exposed generations, compared to the respective controls. In the third Zn exposed generation (F2), no reduction in growth or reproduction compared to the control was observed. This acclimation was reflected in a significantly lower number of differentially transcribed genes, compared to the Zn exposed F0 and F1 generations. PMID- 20580409 TI - Acidification, heavy metal mobility and nutrient accumulation in the soil-plant system of a revegetated acid mine wasteland. AB - A revegetation program was established at an extreme acidic and metal-toxic pyrite/copper mine wasteland in Guangdong Province, PR China using a combination of four native grass species and one non-native woody species. It was continued and monitored for 2 y. The emphasis was on acidification, metal mobility and nutrient accumulation in the soil-plant system. Our results showed the following: (i) the acid-forming potential of the mine soils decreased steadily with time, which might be due to plant root-induced changes inhibiting the oxidization of sulphide minerals; (ii) heavy metal extractability (diethylene-triamine pentaacetic acid-extractable Pb and Zn) in the soils increased with time despite an increase in soil pH, which might be attributed to soil disturbance and plant rhizospheric processes, as well as a consequence of the enhanced metal accumulation in plants over time; and (iii) the vegetation cover increased rapidly with time, and plant development accelerated the accumulation of major nutrients (organic matter, total and ammonium-N, and available P and K). The 2-y field experiment demonstrates that direct seeding/planting of native plant species in combination with lime and manure amelioration is a practical approach to the initial establishment of a self-sustaining vegetation cover on this metalliferous and sulphide-bearing mine wasteland. However, heavy metal accumulation in the soil-plant system should be of great concern, and long-term monitoring of ecological risk must be an integral part of such a restoration scheme. PMID- 20580411 TI - Novel methods for integrated risk assessment of cumulative stressors--results from the NoMiracle project. AB - This special issue covers the main results of the European Sixth Framework Integrated Research project NoMiracle (Novel Methods for Risk Assessment of Cumulative stressors in Europe). New tools to analyse, characterise and quantify the combined risks to health or the environment from multiple stressors are presented or reviewed. Examples of cumulative stressors are mixtures of chemicals alone or in combination with biological or physical environmental factors such as pathogens and climate extremes. Among the main findings, the scientific work points at the importance of time in dealing with toxicity, and in particular the toxicity of chemical mixtures, the natures of the uncertainties associated with risk assessment and the value of visualisation in identifying and quantifying the most relevant risks. A major conclusion of the project is that researchers and regulators should focus on the receptor rather than on the single stressor or combination of agents. There is also a need for more efforts on mechanistic understanding and for a mechanism-based framework for interpreting mixture/multiple stressor effects. The new tools are available on the internet (http://nomiracle.jrc.ec.europa.eu). PMID- 20580410 TI - Assessment of plant-driven removal of emerging organic pollutants by duckweed. AB - Constructed treatment wetlands have the potential to reclaim wastewaters through removal of trace concentrations of emerging organic pollutants, including pharmaceuticals, personal care products, and pesticides. Flask-scale assessments incorporating active and inactivated duckweed were used to screen for plant associated removal of emerging organic pollutants in aquatic plant systems. Removals of four of eight pollutants, specifically atrazine, meta-N,N-diethyl toluamide (DEET), picloram, and clofibric acid, were negligible in all experimental systems, while duckweed actively increased aqueous depletion of fluoxetine, ibuprofen, 2,4-dichlorophenoxyacetic acid, and triclosan. Active plant processes affecting depletion of experimental pollutants included enhancement of microbial degradation of ibuprofen, uptake of fluoxetine, and uptake of degradation products of triclosan and 2,4-dichlorophenoxyacetic acid. Passive plant processes, particularly sorption, also contributed to aqueous depletion of fluoxetine and triclosan. Overall, studies demonstrated that aquatic plants contribute directly and indirectly to the aqueous depletion of emerging organic pollutants in wetland systems through both active and passive processes. PMID- 20580412 TI - Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. AB - OBJECTIVE: The induction or exacerbation of psoriasis in patients treated with tumor necrosis factor (TNF) antagonists is a well-established phenomenon. The goals of this comprehensive literature analysis were to update currently available data regarding this adverse event, to identify any clinical patterns in the cohort of reported patients, and to review the possible immunopathogenesis. METHODS: A systematic literature review was performed utilizing PubMed and Medline databases (1996 to August 2009) searching the index terms "tumor necrosis factor alpha inhibitor," "TNF," "infliximab," "etanercept," "adalimumab," combined with the terms "psoriasis," "pustular," "skin," "rash," "palmoplantar," and "paradoxical." All relevant articles were reviewed. Patients who did not appear to meet accepted classification criteria for their treated disease, who had a more probable explanation or other likely diagnosis for their skin findings or known possible triggering factor for the skin eruption, including infection, were excluded from this analysis. RESULTS: Two hundred seven cases met inclusion criteria for review. Of these, 43% were diagnosed with rheumatoid arthritis, 26% with seronegative spondyloarthropathy, and 20% with inflammatory bowel disease. Mean patient age was 45 years and 65% were female. Fifty-nine percent were being treated with infliximab, 22% with adalimumab, and 19% with etanercept. Lesion morphology included pustular psoriasis in 56%, plaque psoriasis in 50%, and guttate lesions in 12%; 15% experienced lesions of more than 1 type. No statistically significant predisposing factors for the development of new-onset psoriasis were found. Sixty-six percent of patients were able to continue TNF antagonist therapy with psoriasis treatments. The pathogenesis appears to involve disruption of the cytokine milieu with production of unopposed interferon-alpha production by plasmacytoid dendritic cells in genetically predisposed individuals. Genetic polymorphisms may play a role in this paradoxical reaction to TNF blockade. CONCLUSIONS: TNF antagonist induced psoriasis is a well described adverse event without any known predisposing risk factors. Most patients can be managed conservatively without drug withdrawal. Registry data reporting is necessary to define the true incidence and prevalence of this condition. Genomic studies of affected patients may assist with identification of predisposed patients and elucidation of the molecular trigger of this perplexing response. PMID- 20580413 TI - Serum lipoprotein (a) levels in patients with first unprovoked venous thromboembolism is not associated with subsequent risk of recurrent VTE. AB - INTRODUCTION: Case-control studies suggest that elevated lipoprotein (a) (Lp(a)) is a risk factor for first venous thromboembolism (VTE). Lp(a) has not been prospectively investigated as a possible risk factor for recurrent VTE in first unprovoked VTE patients. We sought to determine if serum Lp(a) levels in patients with unprovoked VTE who discontinue anticoagulants after 5 to 7 months of therapy predict VTE recurrence in a prospective cohort study. MATERIALS AND METHODS: Serum Lp(a) measurements were obtained from 510 first unprovoked VTE patients treated for 5 -7 months with anticoagulants in a 12 center study. Patients were subsequently followed for a mean of 16.9 months (SD+/-11.2) for symptomatic VTE recurrence which was independently adjudicated with reference to baseline imaging. RESULTS: There was no significant association between Lp(a) as a continuous variable and recurrent VTE nor in gender stratified subgroups. No statistically significant differences were observed in the median Lp(a) concentrations between patients who recurred and those who did not recur (median (interquartile range): 0.09 g/L (0.17) versus 0.06 g/L (0.11) respectively; p=0.15). The Lp(a) cut-off point of 0.3g/L was not significantly associated with recurrent VTE for the overall population nor in gender stratified subgroups. CONCLUSIONS: Elevated serum Lp(a) does not appear to be associated with recurrent VTE in patients with history of first unprovoked VTE and may not play a role in identifying patients with unprovoked VTE at high risk of recurrence. There was no optimal predictive threshold for the overall population or for sex sub-groups and Lp(a)>or=0.3 g/L was not a significant predictor of recurrent VTE. PMID- 20580414 TI - Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study. AB - BACKGROUND: Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding. MATERIALS AND METHODS: Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2h and 24h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated. RESULTS: Adjusted plasma concentration of fibrinogen (-14+/-6%), and plasma activity of FII (-9+/-6%), FV (-13+/-8%), FX ( 13+/-7%) and FXIII (-9+/-14%) were reduced two hours after surgery compared to baseline (all p<0.001). FVII (+3+/-12%, p=0.34) and FXI (+1+/-19%, p=0.50) were unchanged, while FVIII (+23+/-44%, p=0.006) and FIX (+23+/-17%, p<0.001) increased. Twenty-four hours after surgery fibrinogen (+45+/-27%), FVIII (+93+/ 66%) and FIX (+33+/-26%) were all increased (all p<0.001), while FVII (-37+/-14%, p<0.001), FXI (-4+/-18%, p=0.02) and FXIII (-6+/-15%, p=0.004) were decreased. Median postoperative blood loss was 380 ml/12h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2h after surgery (r=-0.33, p=0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r=-0.34, p=0.009 and r=-0.41, p=0.003, respectively), but not between blood loss and any of the other factors. CONCLUSIONS: There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG. PMID- 20580415 TI - Development and preliminary evaluation of the KIDCLOT PAC QL: a new health related quality of life measure for pediatric long-term anticoagulation therapy. AB - Long term anticoagulation (LTA) is hypothesized to induce treatment dissatisfaction influence quality of life (QOL). QOL is measured by a tool developed specific to the patient condition. Pediatric QOL inventory for children on LTA should assess constructs salient for this population. Identification and evaluation of QOL constructs, critical to improve care, and is accepted as the "gold-standard" measurement for patient-centered outcomes in clinical research. OBJECTIVES: To develop and preliminarily validate a pediatric QOL inventory for children/families receiving LTA. Secondary objective was to determine how anticoagulation disrupts children's life. METHODS: Stage 1: Item/theme generation through focus groups and existing inventories, Stage 2: Item reduction, inventory generation and content validity. Stage 3: Inventory refinement, implementation and reliability testing. Responses were evaluated for variability, internal consistency, and scale structure. Item reduction was based on response rate, item variability, and clinical utility. RESULTS: Two inventories, KIDCLOT-PAC-Child Tween QL and KIDCLOT-PAC Parent-proxy-QL were developed. Content and face validity was assessed by experts, parents, and patients. Internal consistency determined by Cronbach's alpha was good for parent-proxy(0.82) and child(0.89). Pearson correlation was acceptable with >0.5 for test-retest reliability (parent inventory). CONCLUSIONS: KIDCLOT-PAC-QL is the first preliminarily validated inventory to assess QOL in anticoagulated children. The inventory identifies barriers in care and areas for improvement in order to modify care to provide the "best" management (improved QOL associated with safety and efficacy) for children requiring LTA. PMID- 20580416 TI - A cost-effectiveness analysis of diagnostic algorithms of deep vein thrombosis at the emergency department. AB - INTRODUCTION: Suspected cases of deep vein thrombosis are common at emergency departments and they often require extensive and costly diagnostic testing. The objective of this study was to evaluate whether a diagnostic algorithm based upon pre-test probability and D-dimer in diagnosing deep vein thrombosis may be cost effective from a societal perspective in a Swedish setting. MATERIAL AND METHODS: The cost-effectiveness of two alternative diagnostic algorithms were calculated using decision analysis. An algorithm which out ruled deep vein thrombosis among low probability patients with negative D-dimer was compared to a traditional algorithm including compression ultrasonography and/or contrast venography for all patients. For sensitivity analysis, a third reversed algorithm, where D-dimer was followed by pre-test probability, was analyzed. Estimates of probabilities were obtained from a prospective management study, including 357 outpatients with clinical suspicion of deep vein thrombosis. Direct costs were estimated using prices from Scania, Sweden. Indirect costs were estimated using time spent at the local emergency department and gross average wages in Sweden. RESULTS: The total cost of the pre-test probability and D-dimer algorithm was estimated to euro406 per patient and the traditional algorithm was estimated to euro581 per patient. Reversing the order of the score and test resulted in an estimate of euro421 per patient. CONCLUSION: At no significant difference in diagnostic efficacy the algorithm based upon pre-test probability and D-dimer was cost-effective, while the reversed algorithm and diagnostic imaging for all patients were not. PMID- 20580417 TI - Sequence-dependent hematologic side effects of topotecan and cisplatin in persistent or recurrent cervical cancer. AB - OBJECTIVE: This retrospective study evaluates the efficacy and toxicity of topotecan, followed by cisplatin, in patients with persistent or recurrent cervical cancer. METHODS: Twenty-four patients were included in the study. Ninety two cycles of chemotherapy were administered during the study period. Topotecan (0.75 mg/m(2)) was administered as a 30-minute infusion on 3 consecutive days, and cisplatin was given intravenously at a dose of 50 mg/m(2) over 1h on day 3 of every third week. RESULTS: The median number of cycles administered was 3, with a range of 1-8 cycles per patient. There were 4 (16.7%) complete responses, 3 (12.5%) partial responses, and 5 (20.8%) stable disease. All of the patients with a complete response had received palliative radiation or surgery for pain or an isolated solitary recurrence prior to chemotherapy. There were no treatment delays of >7 days per cycle due to hematologic toxicity. There were 59 days of delay (average, 0.6 days per cycle) in 21 of 92 (22.8%) cycles and two episodes of dose reduction (cisplatin, 50% reduction) in 2 patients due to low creatinine clearance (30-60 mL/min). Overall, grade 3/4 anemia, thrombocytopenia, and neutropenia were experienced in 13.1%, 1.1%, and 18.5% of the courses, or 33.4%, 4.2%, and 45.8% of the patients, respectively. CONCLUSION: Combination chemotherapy, consisting of topotecan on days 1-3 and cisplatin on day 3, showed a relatively low rate of hematologic toxicity, as compared with the regimen of topotecan on days 1-3 and cisplatin on day 1, as used in previous studies. PMID- 20580418 TI - Heat shock proteins in ovarian cancer: a potential target for therapy. AB - Ovarian cancer is the leading cause of death from gynecologic cancer in Western countries. Most of the patients are chemosensitive, and they will present a complete response after initial treatment, but most of them will relapse within 2 years. The resistance to standard chemotherapy represents a significant clinical challenge. Therefore, a better understanding of the molecular mechanisms involved in the drug resistance should allow to improve the treatment in this disease. Interestingly, recent data showed essential roles of heat shock proteins (HSPs) in various processes of carcinogenesis and their association with resistance to anticancer drugs. Here, we report the main investigations on HSPs in ovarian cancer with specific emphasis on clinical application. PMID- 20580419 TI - Modeling colorant leakage techniques: application to endodontics. AB - OBJECTIVES: Our aim was to improve the comprehension of in vitro tracer leakage studies and to determine in which conditions such studies can be reliable. We aimed to develop different theoretical models to describe either an initially dry or a wet interface (slit) between sealer and dentin. METHODOLOGY: Equations based on physical laws were derived to model theoretically in vitro tracer penetration. For the dry interfaces, atmospheric, hydrostatic, tracer gravimetric, capillary and internal air pressures were considered as the underlying forces that control tracer penetration. For wet interfaces, the laws of diffusion were used to model colorant penetration. RESULTS: In both cases penetration is influenced by the width of the interface and by the size of the colorant. Calculations for dry conditions have shown that penetration is quick, mainly driven by the capillary pressure, and the penetration increases as the width of the interface diminishes. Dentinal tubules and the extent of their interconnection modify the penetration depth. For wet conditions, tracer size is the main factor controlling the penetration length and speed (the bigger the tracer, the slower the penetration). SIGNIFICANCE: Our model calculations demonstrate that tracer penetration studies have to be performed under strict experimental conditions. Dry and wet interfaces are two extreme cases with very different tracer penetration modes. In vitro colorant penetration tests should be performed in both of these conditions avoiding cases where the slit contains both air and water. Theses models can be adapted to other dental situations as well. PMID- 20580420 TI - Substance use among middle school students: associations with self-rated and peer nominated popularity. AB - Associations of popularity with adolescent substance use were examined among 1793 6-8th grade students who completed an in-school survey. Popularity was assessed through both self-ratings and peer nominations. Students who scored higher on either measure of popularity were more likely to be lifetime cigarette smokers, drinkers, and marijuana users, as well as past month drinkers. Self-rated popularity was positively associated with past month marijuana use and heavy drinking, and peer-nominated popularity showed a quadratic association with past month heavy drinking. These results extend previous work and highlight that popularity, whether based on self-perceptions or peer friendship nominations, is a risk factor for substance use during middle school. Given the substantial increase in peer influence during early adolescence, prevention program effectiveness may be enhanced by addressing popularity as a risk factor for substance use or working with popular students to be peer leaders to influence social norms and promote healthier choices. PMID- 20580421 TI - Diabetic retinopathy. AB - Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising. PMID- 20580424 TI - Vitamin C and E to prevent pre-eclampsia in diabetic women. PMID- 20580422 TI - Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. AB - BACKGROUND: Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin. METHODS: In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA(1c)) of 8.5% (SD 1.1), fasting plasma glucose of 9.1 mmol/L (2.6), and weight of 88.0 kg (20.1), were enrolled and treated at 72 sites in the USA, India, and Mexico. Patients were randomly assigned to receive: 2 mg injected exenatide once weekly plus oral placebo once daily; 100 mg oral sitagliptin once daily plus injected placebo once weekly; or 45 mg oral pioglitazone once daily plus injected placebo once weekly. Primary endpoint was change in HbA(1c) between baseline and week 26. Analysis was by intention to treat, for all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00637273. FINDINGS: 170 patients were assigned to receive once weekly exenatide, 172 to receive sitagliptin, and 172 to receive pioglitazone. 491 patients received at least one dose of study drug and were included in the intention-to-treat analysis (160 on exenatide, 166 on sitagliptin, and 165 on pioglitazone). Treatment with exenatide reduced HbA(1c) (least square mean -1.5%, 95% CI -1.7 to -1.4) significantly more than did sitagliptin (-0.9%, -1.1 to 0.7) or pioglitazone (-1.2%, -1.4 to -1.0). Treatment differences were -0.6% (95% CI -0.9 to -0.4, p<0.0001) for exenatide versus sitagliptin, and -0.3% (-0.6 to 0.1, p=0.0165) for exenatide versus pioglitazone. Weight loss with exenatide ( 2.3 kg, 95% CI-2.9 to -1.7) was significantly greater than with sitagliptin (difference -1.5 kg, 95% CI -2.4 to -0.7, p=0.0002) or pioglitazone (difference 5.1 kg, -5.9 to -4.3, p<0.0001). No episodes of major hypoglycaemia occurred. The most frequent adverse events with exenatide and sitagliptin were nausea (n=38, 24%, and n=16, 10%, respectively) and diarrhoea (n=29, 18%, and n=16, 10%, respectively); upper-respiratory-tract infection (n=17, 10%) and peripheral oedema (n=13, 8%) were the most frequent events with pioglitazone. INTERPRETATION: The goal of many clinicians who manage diabetes is to achieve optimum glucose control alongside weight loss and a minimum number of hypoglycaemic episodes. Addition of exenatide once weekly to metformin achieved this goal more often than did addition of maximum daily doses of either sitagliptin or pioglitazone. FUNDING: Amylin Pharmaceuticals and Eli Lilly. PMID- 20580425 TI - Individualised incretin-based treatment for type 2 diabetes. PMID- 20580426 TI - On the role of oxygen vacancies and lattice strain in the tetragonal to monoclinic transformation in alumina/zirconia composites and improved environmental stability. AB - The aim of this paper is to clarify at the nanometer scale the relevant factors influencing the hydrothermal resistance to polymorphic transformation of alumina/zirconia composites, primary candidates for artificial joint applications. The topographic distribution of oxygen vacancies and lattice strain on the composite surface were visualized by means of cathodoluminescence spectroscopy and mapped as a function of exposure time in a thermally activated water vapor environment (i.e., simulating the exposure in human body). Systematically monitoring the optical activity of oxygen vacancies in both alumina and zirconia phases also revealed the effect of surface lattice strain accumulation on the kinetics of polymorphic transformation. From the presented data, an explicit role is evinced for surface oxygen vacancy formation in the alumina matrix, an important step in the complex cascade of mechanochemical events determining the superior environmental resistance of the composite. PMID- 20580423 TI - Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. AB - BACKGROUND: Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. METHODS: We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. FINDINGS: Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported. INTERPRETATION: Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. FUNDING: The Wellcome Trust. PMID- 20580427 TI - Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique. AB - A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. PMID- 20580428 TI - Effects of extracellular matrix protein functionalized fluid membrane on cell adhesion and matrix remodeling. AB - In order to study cellular responses and extracellular matrix protein remodeling mediated by biomaterials coating, we proposed a biomimetic construct containing protein-conjugated supported lipid bilayers (SLBs) as a cell culture platform. Single or multi-component proteins-bound SLBs were fabricated by conjugating type I collagen and/or fibronectin on the N-hydroxysulfosuccinimide-functionalized SLBs. The proposed protein-conjugated systems were quantitatively characterized by the quartz crystal microbalance with dissipation. NIH 3T3 fibroblasts were cultured on the model constructs and on oxygen plasma pretreated polystyrene (PSo) for parallel comparison. The retards of mobility of SLB after protein conjugation and cell culture were estimated by fluorescence recovery after photobleaching. The resulting cell morphology, adsorption kinetics and somatic dynamics were examined microscopically. We found that, on the SLB based cultures, the largest spreading size and cell number counts of 3T3 fibroblasts were found on the fibronectin containing surfaces. However, on the protein-coated PSo surfaces, no such distinguishable differences can be observed on all protein contents. Immunofluorescent staining results revealed that adsorption of endogenously produced fibronectin by 3T3 cells on PSo based surfaces is significantly more than that on SLB based surfaces. This suggests that the anti fouling nature of underneath SLBs have played an important role in preventing 3T3 cells from effectively remodeling their microenvironment, whereas cells can easily remodel the nonspecific adsorption prone surfaces such as PSo based platforms. In summary, the protein conjugated SLB surfaces can serve as a platform for determining and regulating cell specific binding and subsequent signaling events with extracellular environments. PMID- 20580429 TI - Disassemblable micelles based on reduction-degradable amphiphilic graft copolymers for intracellular delivery of doxorubicin. AB - Disassemblable micelles for intracellular delivery of doxorubicin were developed based on a reduction-degradable amphiphilic polyamide amine-g-polyethylene glycol graft copolymer containing disulfide linkages throughout the main chain. The micelles are spherical of less than 50 nm in diameter, and can load doxorubicin in the core with drug loading content up to 20%. The micelles are stable in normal physiological condition, and quickly disassemble in reductive condition due to the cleavage of the disulfide linkages. The drug release of the micelles in normal condition is less than 25% within 24 h, whereas in the presence of reductive agent, DTT, the micelles can quickly release the entire loaded drug within 10 h. CLSM observation showed that the micelles can effectively deliver the drug cargo into nuclei after internalized through endocytosis. Cytotoxicity of the drug-loaded disassemblable micelles was demonstrated using human cervical cancer cell line (HeLa) and human liver carcinoma cell line (HepG2). PMID- 20580430 TI - Tuning the mechanical properties of bioreducible multilayer films for improved cell adhesion and transfection activity. AB - A simple approach to the mechanical modulation of layer-by-layer (LbL) films is through manipulation of the film assembly. Here, we report results based on altering the salt concentration during film assembly and its effect on film rigidity. Based on changes in film rigidity, cell adhesion characteristics and transfection activity were investigated in vitro. LbL films consisting of reducible hyperbranched poly(amide amine) (RHB) have been implemented along with DNA for investigating fibroblast adhesion on [RHB/DNA](n/2) films with varying rigidities. The rigidity was varied by changing the ionic concentration of the deposition solution between 0.01 m NaCl and 1.0 m NaCl. Molecular force probe (MFP) measurements were performed to measure the apparent Young's modulus, E(APP), of the films in situ. Cell adhesion and stress-fiber characteristics were investigated using total internal reflectance microscopy (TIRF-M). The average cell peripheral area, fiber density and average fiber length during 5 days of cell growth on films with either low (below 2.0 MPa) or high (above 2.0 MPa) film elastic modulus were investigated. Transfection studies were performed using gfpDNA and SEAP-DNA to investigate if changes in cell adhesion affect transfection activity. Furthermore, cell proliferation and cytotoxicity studies were used to investigate cellular viability over a week. The results have shown that surface modification of bioreducible LbL films of controlled thickness and roughness promotes cellular adhesion, stress-fiber growth and increased transfection activity without the need for an additional adhesive protein pre coating of the surface or chemical cross-linking of the film. PMID- 20580431 TI - Highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy. AB - Recently, we showed that incorporation of poly[2-(2-ethoxy)ethoxyethyl vinyl ether (EOEOVE)], which exhibits a lower critical solution temperature around 40 degrees C, provides temperature-sensitive properties to stable liposomes. In this study, we applied this thermosensitive polymer for preparation of temperature sensitive liposomes for tumor-specific chemotherapy with doxorubicin (DOX). We prepared liposomes consisting of PEG-lipid, egg yolk phosphatidylcholine, cholesterol and copoly(EOEOVE-block-octadecyl vinyl ether), which was synthesized as poly(EOEOVE) having anchors for fixation onto liposome membrane. The copolymer incorporated liposomes were stable and retained DOX in their inside below physiological temperatures. However, they exhibited a significant release of encapsulated DOX above 40 degrees C and released DOX almost completely within 1 min at 45 degrees C. The copolymer-modified liposomes exhibited a long circulating property and biodistribution similar to that of PEG-modified liposomes. The copolymer-modified liposomes loaded with DOX were injected intravenously into tumor-bearing mice. Tumor growth was strongly suppressed when the tumor site was heated to 45 degrees C for 10 min at 6-12 h after injection. However, injection of the liposomes exhibited only slight tumor-suppressive effects as long as mild heating was not applied to the target site. The highly temperature-sensitive properties of the copolymer-incorporated liposomes might contribute to establishment of tumor-selective and effective chemotherapy. PMID- 20580432 TI - Acute toxicity of diphacinone in Northern bobwhite: effects on survival and blood clotting. AB - The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell's Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species. PMID- 20580433 TI - Formation of a combined Ca/Cd toxicity on lifespan of nematode Caenorhabditis elegans. AB - We investigated the possible formation of combined toxicity from Ca/Cd exposure on nematode lifespan. Ca exposure at concentrations more than 1.56 mM significantly reduced lifespan, accelerated aging-related declines, and induced severe stress response in wild-type nematodes. Combined Ca (25 mM)/Cd (200 microM) exposure decreased the lifespans compared to Cd (200 microM) exposure; whereas no lifespan differences were found between Ca (1.56 mM)/Cd (200 microM) exposure and Cd (200 microM) exposure. Combined Ca (25 mM)/Cd (200 microM) exposure caused a more significant induction of hsp-16.2::gfp expression, and a more severe increase in oxidative damage than Cd (200 microM) exposure. Moreover, mutation of mev-1, encoding a subunit of succinate dehydrogenase cytochrome b, enhanced the combined Ca/Cd toxicity on lifespan. Furthermore, mutation of daf 16, encoding a fork-head-family transcription factor, enhanced the combined Ca/Cd toxicity on lifespan, and mutation of daf-2, encoding an insulin receptor-like protein, alleviated the combined Ca/Cd toxicity on lifespan. PMID- 20580434 TI - Human perforin permeabilizing activity, but not binding to lipid membranes, is affected by pH. AB - The various steps that perforin (PFN), a critical mediator of innate immune response, undertakes to form a transmembrane pore remains poorly understood. We have used surface plasmon resonance (SPR) to dissect mechanism of pore formation. The membrane association of PFN was calcium dependent irrespective of pH. However, PFN does not permeabilize large or giant unilamellar vesicles (GUV) at pH 5.5 even though the monomers bind to the membranes in the presence of calcium. It was possible to activate adsorbed PFN and to induce membrane permeabilization by simply raising pH to a physiological level (pH 7.4). These results were independently confirmed on GUV and Jurkat cells. The conformational state of PFN at either pH was further assessed with monoclonal antibodies Pf-80 and Pf-344. Pf 344 maps to a linear epitope within region 373-388 of epidermal growth factor (EGF)-like domain while the Pf-80 appears to recognize a conformational epitope. Pf-344 interacts with the EGF-like domain after PFN monomers undergo pore formation, the site recognized by Pf-80 is only accessible at acidic but not neutral pH. Thus, the Pf-80 mAb likely interacts with a region of the monomer that participates in oligomerization prior to insertion of the monomer into the lipid bilayer and thus may have therapeutic utility against PFN-mediated immunopathology. PMID- 20580435 TI - Personality and the perception of health and happiness. AB - BACKGROUND: Health is a state of physical, mental, and social well-being. Personality traits measure individual differences in adaptive functioning and mental health, but little is known about how well personality accounts for health's affective aspects (i.e., "happiness") and its non-affective aspects (i.e., "wellness") in the general population. METHODS: 1102 volunteer representatives of the Sharon area of Israel completed the Temperament and Character Inventory (TCI), the Positive and Negative Affect Scale (PANAS), the Satisfaction with Life Scale (SWLS), the Multidimensional Scale of Perceived Social Support (PSS), and the subjective health assessment of the General Health Questionnaire (GHQ). Multidimensional personality profiles were used to evaluate the linear and non-linear effects of interactions among dimensions on different aspects of well-being. RESULTS: Self-directedness was strongly associated with all aspects of well-being regardless of interactions with other dimensions. Cooperativeness was strongly associated with perceived social support, and weakly with other aspects of well-being, particularly when Self-directedness was low. Self-transcendence was strongly associated with positive emotions when the influence of the other character dimensions was taken into account. Personality explained nearly half the variance in happiness and more than one-third of the variance in wellness. LIMITATIONS: Our data are cross-sectional and self reported, so they are subject to personal perceptual bias. CONCLUSIONS: The emotional, social, and physical aspects of well-being are interdependent, but specific configurations of TCI Self-directedness, Cooperativeness, and Self transcendence influence them differentially. Interactions among different combinations of character traits have strong effects on the perception of both wellness and happiness. PMID- 20580436 TI - Train suicides in The Netherlands. AB - BACKGROUND: Little is known about train suicide and factors influencing its prevalence. This study tests the hypotheses that railway density, railway transportation volume, familiarity with railway transportation and population density contribute to train suicide. It also tests the relationship between train suicide and general population suicide and examines the prevalence and the characteristics of high-risk locations and their contribution to the grand total of train suicides. METHODS: Trends in train suicides were compared with trends in railway track length, train kilometres, passenger kilometres and national suicide figures over the period 1950-2007. The geographical distribution over the national network over the period 1980-2007 was studied. Data were obtained from The Netherlands Railways, Prorail and Statistics Netherlands. RESULTS: 1. The incidence of train suicides is unrelated to railway parameters. 2. Being familiar with railway transportation as a passenger is not a contributory factor. 3. Train suicide rates are unrelated to regional population density. 4. The incidence of train suicides parallels that of general population suicides. 5. Half of the train suicides took place at a limited number of locations, the most important of which were situated within a village or town and were close to a psychiatric hospital. LIMITATIONS: Most conclusions are based on correlational relationships between variables. CONCLUSIONS: 1. Train suicide trends reflect trends in general population suicides. 2. Increased train transportation does not lead to more train suicides. 3. The prevention of train suicide at high-risk locations (HRLs) in built-up areas and near psychiatric hospitals deserves first priority. PMID- 20580437 TI - Measuring the urge to self-injure: preliminary data from a clinical sample. AB - The purpose of this study was to evaluate the psychometric properties of a measure, the Alexian Brothers Urge to Self-Injure Scale (ABUSI). The ABUSI was designed to assess the severity of the urge to engage in non-suicidal self injury. Non-suicidal self-injury is the deliberate damage of body tissue that is not sanctioned by society and is devoid of an active intent to die. Participants included 386 adolescent and adult patients (90.7% female, 86.3% non-Hispanic white) admitted to a psychiatric facility for the treatment of non-suicidal self injury. Patients were administered the ABUSI as well as measures of the frequency of self-injury, quality of life and satisfaction, functional impairment, and suicidal ideation at admission and discharge as part of routine clinical assessment. Results provide preliminary support for the reliability and validity of the ABUSI as a measure of the intensity of the urge to self-injure. Specifically, the ABUSI demonstrated adequate internal consistency, test-retest reliability, sensitivity to change, and convergent, predictive, and incremental validity. Findings suggest the ABUSI is a promising tool for both clinical assessment and research. PMID- 20580438 TI - Validation of endogenous reference genes for RT-qPCR normalisation in bovine lymphoid cells (BL-3) infected with Bovine Viral Diarrhoea Virus (BVDV). AB - Reverse transcription quantitative PCR (RT-qPCR) is a highly sensitive tool that can be used for accurate and reliable gene expression analysis; however, careful normalisation to a set of stably expressed endogenous reference genes is essential. Expression levels of many reference genes in RT-qPCR analyses can be extremely variable under different experimental conditions, producing potentially erroneous results (Bustin, 2002). This limitation can be overcome with a systematic evaluation of candidate reference genes to determine the most stable. In the present study eight candidate reference genes were evaluated in a bovine lymphoid (BL-3) cell culture system over seven different time points in response to three different Bovine Viral Diarrhoea Virus (BVDV) strains. Data were analysed using BestKeeper (Pfaffl et al., 2004), geNorm (Vandesompele et al., 2002), and NormFinder (Andersen et al., 2004) validation programs and results enable the candidate reference genes to be ranked from most to least stable. Quantification cycle (C(q)) variability was determined between samples, i.e. between treatment groups and time points, and variability was also observed between the three validation programs. The reference gene combination of beta actin and hypoxanthine-guanine phosphoribosyl transferase (HPRT) was found to be the most stable in Norm Finder. BestKeeper and geNorm both demonstrated beta microglobulin and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase (YWHAZ) as the most stable. The determination of a stable set of reference genes in the BL-3 cell culture system facilitates analysis of expression levels for appropriate genes of interest. This study further emphasises the need to accurately validate candidate reference genes before use in gene expression RT-qPCR studies. PMID- 20580439 TI - Clathrin-mediated endocytosis and transcytosis of enterotoxigenic Escherichia coli F4 fimbriae in porcine intestinal epithelial cells. AB - Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhea in neonatal and recently weaned piglets. Previously, we demonstrated that oral immunization of F4 receptor positive piglets with purified F4 fimbriae induces a protective F4 specific intestinal immune response. However, in F4 receptor negative animals no F4-specific immune response can be elicited, indicating that the induction of an F4-specific mucosal immune response upon oral immunisation is receptor-dependent. Although F4 fimbriae undergo transcytosis across the intestinal epithelium in vivo, the endocytosis pathways used remain unknown. In the present study, we characterized the internalization of F4 fimbriae in the porcine intestinal epithelial cell line IPEC-J2. The results in the present study demonstrate that F4 fimbriae are internalized through a clathrin-dependent pathway. Furthermore, our results suggest that F4 fimbriae are transcytosed across differentiated IPEC J2 cells. This receptor-dependent transcytosis of F4 fimbriae may explain the immunogenicity of these fimbriae upon oral administration in vivo. PMID- 20580441 TI - CXCR4-mediated glutamate exocytosis from astrocytes. AB - The role of astrocytes as structural and metabolic support for neurons is known since the beginning of the last century. Because of their strategic localization between neurons and capillaries they can monitor and control the level of synaptic activity by providing energetic metabolites to neurons and remove excess of neurotransmitters. During the last two decades number of papers further established that the astrocytic plasma-membrane G-protein coupled receptors (GPCR) can sense external inputs (such as the spillover of neurotransmitters) and transduce them as intracellular calcium elevations and release of chemical transmitters such as glutamate. The chemokine CXCR4 receptor is a GPCR widely expressed on glial cells (especially astrocytes and microglia). Activation of the astrocytic CXCR4 by its natural ligand CXCL12 (or SDF1 alpha) results in a long chain of intracellular and extracellular events (including the release of the pro inflammatory cytokine TNFalpha and prostanglandins) leading to glutamate release. The emerging role of CXCR4-CXCL12 signalling axis in brain physiology came from the recent observation that glutamate in astrocytes is released via a regulated exocytosis process and occurs with a relatively fast time-scale, in the order of few hundred milliseconds. Taking into account that astrocytes are electrically non-excitable and thus exocytosis rely only on a signalling pathway that involves the release Ca(2+) from the internal stores, these results suggested a close relationship between sites of Ca(2+) release and those of fusion events. Indeed, a recent observation describes structural sub-membrane microdomains where fast ER dependent calcium elevations occur in spatial and temporal correlation with fusion events. PMID- 20580440 TI - Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice. AB - Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory immune response directed against myelin antigens of the central nervous system. In its murine model, EAE, Th17 cells play an important role in disease pathogenesis. These cells can induce blood-brain barrier disruption and CNS immune cells activation, due to the capacity to secrete high levels of IL-17 and IL-22 in an IL-6+TGF-beta dependent manner. Thus, using the oral tolerance model, by which 200 MUg of MOG 35-55 is given orally to C57BL/6 mice prior to immunization, we showed that the percentage of Th17 cells as well as IL-17 secretion is reduced both in the periphery and also in the CNS of orally tolerated animals. Altogether, our data corroborates with the pathogenic role of IL-17 and IFN-gamma in EAE, as its reduction after oral tolerance, leads to an overall reduction of pro-inflammatory cytokines, such as IL-1alpha, IL-6, IL-9, IL-12p70 and the chemokines MIP-1beta, RANTES, Eotaxin and KC in the CNS. It is noteworthy that this was associated to an increase in IL-10 levels. Thus, our data clearly show that disease suppression after oral tolerance induction, correlates with reduction in target organ inflammation, that may be caused by a reduced Th1/Th17 response. PMID- 20580442 TI - Common variants of the neuropeptide expressing tachykinin genes and susceptibility to asthma: a case-control study. AB - Since tachykinins appear to be involved in the pathogenesis of allergic asthma, we investigated a possible association between 28 single nucleotide polymorphisms of the tachykinin genes TAC1, TAC3 and TAC4, and asthma susceptibility. A case control study was conducted on 102 patients and 100 healthy subjects from the Canary Islands (Spain). A significant association with asthma was observed for two SNPs: rs2291855 in the TAC3 gene conferring asthma protection (Odds ratio [OR]: 0.46; 95% Confidence Interval [CI]: 0.22-0.97; P=0.038), and rs4794068 in the TAC4 gene associated with an increased risk for asthma (OR: 1.94; 95% CI: 1.06-3.54; P=0.03). The present study represents a preliminary step in elucidating the association between tachykinin gene polymorphisms and asthma susceptibility. PMID- 20580443 TI - Eustachian tube-tensor veli palatini muscle-cranial base relationships in children and adults: an osteological study. AB - OBJECTIVE: The vector relationships between the Eustachian tube, Tensor veli palatini muscle and cranial base constrain the efficiency of middle ear pressure regulation and are required parameters for computational modeling of Eustachian tube function. Here, those relationships were reconstructed from skulls and compared between children and adults. METHOD: Reconstructions were made using modifications of previously described techniques for 18 child skulls aged 3-4 years and 20 adult skulls (10 females, 10 males; >18 years). Measured and calculated variables were compared between groups using a Student's t-test. RESULTS: Consistent with previous reports, certain variables for adult skulls exhibited sexual dimorphism. Between children and adults, significant differences were documented for measures of cranial base length and width; hard palate width; nasopharyngeal height, width and depth; Eustachian tube length; the maximum and minimum Tensor veli palatini muscle lengths; the angles of deviation of the Tensor veli palatini muscle from the Eustachian tube, and the surface area of the Tensor veli palatini muscle. There were no between-group differences in the angle of Eustachian tube decent from the cranial base, Eustachian tube deviation from the parasagittal plane or the lateral component of the Tensor veli palatine muscle-Eustachian tube angle. CONCLUSIONS: The differences between children and adults that could account for the observed poorer Eustachian tube function in children include their shorter Eustachian tube, lesser Tensor veli palatine muscle-Eustachian tube vectors, and the lesser Tensor veli palatine muscle surface area. Other observed differences are attributable to growth and development of the craniofacial complex. PMID- 20580444 TI - Persistent primitive hepatic venous plexus in a child with scimitar syndrome. PMID- 20580445 TI - High mortality among heart failure patients treated with antidepressants. PMID- 20580446 TI - Impact of coronary artery calcium on cardiovascular risk categorization and lipid lowering drug eligibility in asymptomatic hypercholesterolemic men. AB - BACKGROUND: Application of coronary artery calcium (CAC) for stratifying coronary heart disease (CHD) risk may change the proportion of subjects eligible for risk reduction treatment and decrease cost-effectiveness of primary prevention. We therefore aimed to analyze the impact of CAC on CHD risk categorization. METHODS: We measured CAC with electron beam computed tomography in 500 asymptomatic untreated hypercholesterolemic men and re-calibrated 10-year Framingham CHD risk by adding CAC score information (post CAC test risk) via an algorithm integrating relative risk and expected distribution of CAC in the population tested. Proportions of low (<10%), intermediate (10-20%) and high (>20%) risk categories, and of eligibility for lipid-lowering treatment, were compared between Framingham risk and post CAC test risk. RESULTS: In the overall population, post CAC test risk calculation changed risk categorization defined by Framingham assessment alone, with 10% more low risk and 10% less intermediate risk (p<0.01). Risk reclassifications were bidirectional since 30% of high and 30% of intermediate Framingham risk were downgraded to intermediate and low risk categories respectively, while 11% of low and 14% of intermediate Framingham risk were upgraded to intermediate and high-risk categories respectively. Post CAC test risk did not change the proportion of Framingham-based lipid-lowering treatment eligibility in the overall population but decreased it by 8% in intermediate Framingham risk subgroup (p<0.05). CONCLUSIONS: Addition of CAC to risk prediction resulted rather in downgrading than in upgrading risk and did not change treatment eligibility, except in intermediate risk subjects, less frequently eligible for treatment. PMID- 20580447 TI - Expression of spliceosome assembly factor SC-35 in TUNEL-positive atrial cardiomyocytes in mitral and tricuspid regurgitation: viability of atrial cardiomyocytes. AB - BACKGROUND: Most of the atrial cardiomyocytes with positive terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labelling (TUNEL) reaction are not apoptotic in patients with mitral and tricuspid valve diseases. The TUNEL-positive myocytes with expression of spliceosome assembly factor SC-35, an indicator of increased RNA synthesis, should be living cardiomyocytes. METHODS: This study analyzed twenty-three patients with significant mitral and tricuspid regurgitation. Fifteen patients had persistent atrial fibrillation, and eight had sinus rhythm. Atrial appendageal tissues were obtained during surgery. Immunohistochemical study was performed. RESULTS: Immunohistochemical study of fibrillating right atrial myocardium demonstrated that 44.8 +/- 24.6% of myocytes had TUNEL-positive nuclei whereas 39.4 +/- 21.4% of myocytes had TUNEL-positive nuclei in sinus right atrial myocardium (p=0.682). However, most (81.6%) nuclei of TUNEL-positive myocytes in the fibrillating right atria also expressed proliferating cell nuclear antigen (PCNA), an indicator of DNA replication and repair, and most nuclei (91.8%) of TUNEL-positive myocytes also expressed SC-35. In fibrillating left atria, most (88.1%) nuclei of TUNEL positive myocytes also expressed SC-35. Similarly, in sinus right atrial myocardium, most (78.0%) nuclei of TUNEL-positive myocytes expressed PCNA, and most (91.4%) nuclei of TUNEL-positive myocytes also expressed SC-35, but none expressed Ki-67, a replication-associated antigen. Additionally, the percentage of TUNEL-positive myocytes in the right atria significantly and positively correlated with the percentage of PCNA-positive myocytes (r=0.826, p<0.001) and SC-35 positive myocytes (r=0.713, p<0.001). CONCLUSIONS: Most TUNEL-positive atrial cardiomyocytes in patients with mitral and tricuspid regurgitation are living cardiomyocytes. PMID- 20580448 TI - Is China finally going to ban cigarette smoking? PMID- 20580449 TI - Pericardial effusion triage. PMID- 20580450 TI - Should we resynchronize all left bundle branch blocks in patients presenting with acute heart failure? PMID- 20580451 TI - Catheter-based transendocardial microbubble and pEGFP delivery combination of intracardiac ultrasonic exposure enhances EGFP gene expression. PMID- 20580452 TI - Cerebellar haemorrhage triggered Takotsubo-like left ventricular dysfunction syndrome. PMID- 20580453 TI - A case of asymptomatic patient with hyperthyroidism documented the onset of Takotsubo cardiomyopathy by Holter monitoring. PMID- 20580454 TI - Spatial and spatio-temporal clustering of overall and serovar-specific Leptospira microscopic agglutination test (MAT) seropositivity among dogs in the United States from 2000 through 2007. AB - Leptospirosis is a re-emerging disease of dogs in the United States (U.S.). This paper reports the findings of a retrospective study conducted to determine if seroreactivity to Leptospira microscopic agglutination test (MAT) among dogs in the U.S. clustered in space and time. The study utilized canine sera submitted to a commercial laboratory for leptospiral MAT from January 2000 through December 2007. There were 31,869 serum samples submitted by veterinarians from 3156 zip code locations across the U.S. Results of MAT were considered positive at titers of > or = 1:1600. Spatial and spatial-temporal scan statistics were used to identify statistically significant clusters of seroreactivity to Leptospira (overall and individual serovars) using recorded test request dates and locations of the centroid of the zip code reported for each serum sample. There were 2469 positive MAT results with a titer > or = 1:1600 to at least one of seven Leptospira serovars. Two relevant spatial clusters of 26.3 and 246.5 km radius were identified (P=0.001). The primary cluster was located in the northeastern part of Illinois including Chicago and surrounding areas (232 [14.4%] of 1612 MAT positive; RR=1.95). The secondary cluster covered the central part of Texas (292 [12.62%] of 2314 MAT positive; RR=1.71). Eight space-time clusters of overall MAT positivity were identified (29-335 km radius; P=0.001-0.048 and RR=3.98-24.69) that covered different geographic locations for different time points. Spatial and space-time clusters for individual serovars were also identified for six serovars: eight each of Grippotyphosa and Pomona, seven of Bratislava, five of Autumnalis, and three each of Icterohaemorrhagiae and Canicola. In conclusion Leptospira seropositivity in dogs tended to have distinctive clusters in space and space-time. Most of the space-time clusters of overall Leptospira MAT seropositivity were associated with cluster events for individual serovars. Further investigation is warranted to explain individual serovar clusters detected in this study, as a complex interaction of incidental host, environment and reservoir host may be responsible for the occurrence of these serovar clusters. PMID- 20580455 TI - Can human movement analysis contribute to usability understanding? AB - Nowadays human-machine interfaces are evaluated using different methodologies. These methodologies rarely consider the human movements involved in the interaction, and if so, the movements are considered in a simplistic manner. Another often neglected aspect is the relationship between the learning process and the use of the interface. Traditional approaches of cognitive modeling consider learning as just one continuous process. However there is some current evidence of concurrent processes on different time scales. This paper aims to answer, with experimental measurements, if learning actually implies a set of concurrent processes, if those processes are related to the coordinative aspects of hand movement, and how this can vary between young adult and elderly users. Two different interfaces, a washing machine and a domotic system, were analyzed with 23 and 20 people, respectively, classified as men or women and elderly (over 55) or adult (between 40 and 50). The results of the study provide support for the existence of different concurrent processes in learning, previously demonstrated for motor tasks. Moreover, the learning process is actually associated with changes in movement patterns. Finally, the results show that the progression of the learning process depends on age, although elderly people are equally capable of learning to use technological systems as young adults. PMID- 20580456 TI - An acid/alkaline stress and the addition of amino acids induce a prolonged viability of Lactobacillus plantarum loaded into alginate gel. AB - This study reports on the investigation on the effects of the conditions used throughout the step of biomass production on the survival of Lactobacillus plantarum loaded into alginate gels. L. plantarum was grown under different conditions (MRS or a laboratory medium-LB(2)-at acidic or alkaline pHs, with NaCl, phenols, vitamins or amino acids) and immobilized in sodium alginate; cell number was evaluated throughout the storage and death (delta(stand)) and first reduction times (delta) were calculated. The storage of alginate gels at 4 degrees C prolonged cell viability up to 60 days (ca. 20 days for cells produced in MRS and stored at 30 degrees C); however, a similar prolongation was achieved for cells produced in LB(2) adjusted to pH 5.0 and 9.0 or added with amino acids (death time>50-60 days). PMID- 20580457 TI - Molecular basis and transferability of tetracycline resistance in Enterococcus italicus LMG 22195 from fermented milk. AB - A tetracycline-resistant Enterococcus italicus strain from fermented milk, LMG 22195, was found to contain a tet(S) gene located on a plasmid of approximately 20kb. Filter mating demonstrated that the tet(S) gene was transferable from LMG 22195 to the recipient Enterococcus faecalis JH2-2. PCR-based detection and Southern blot experiments revealed that the confirmed transconjugants acquired the tet(S)-carrying plasmid. Similar to the donor strain, transconjugants displayed a tetracycline MIC of 64 microg/ml. Results of this study suggest that E. italicus, like other enterococcal species, is able to disseminate antibiotic resistance genes, although a more definitive proof on this statement will be provided when a higher number of strains will be tested. Because of the recent isolation of E. italicus from human clinical specimens and its concomitant presence in various dairy products, the ability of this organism to horizontally transfer tet(S) or other resistance genes may potentially pose safety concerns, especially for its possible use in food fermentations. PMID- 20580458 TI - Safety and effectiveness of flexor tenotomies to heal toe ulcers in persons with diabetes. AB - AIM: To evaluate the effectiveness and safety of percutaneous tenotomy of the flexor digitorum longus to heal neuropathic ulcers on the tip of the toe. METHODS: We retrospectively reviewed a cohort of 48 patients with 58 tenotomy procedures with diabetes related neuropathy and ulceration at the tip of the toe. Subjects were treated with tenotomy of the flexor digitorum longus. We then evaluated healing of the ulceration and any adverse events including recurrence, infection, healing failure, and amputation. RESULTS: 98.3% of the ulcerations healed. Mean ulcer healing time was 40+/-52 days. 12.1% had a recurrence of ulceration at the same site. Mean time to recurrence was 13.9 months. Five percent had post-operative soft tissue infection. Two patients had amputation of the digit; both had pre-existing osteomyelitis. Mean follow up was 28 months. CONCLUSION: Flexor tenotomy is a safe, simple procedure, which can enhance patients' healing potential with very little risk. PMID- 20580459 TI - The relationship between arterial elasticity and lipid profile in people with type 1 diabetes mellitus. AB - A cross-sectional study was carried out to assess small (SAEI) and large (LAEI) arterial elasticity indexes of individuals with T1DM, and its relationship with their lipid profile. There were associations between SAEI and total cholesterol and waist-hip ratio (R(2)=0.29). Most of the individuals investigated showed low measures of SAEI. PMID- 20580460 TI - Meta-analysis of performance of Kings's College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure. AB - BACKGROUND & AIMS: Current techniques for predicting outcome and requirement for emergency liver transplantation (ELT) in acute liver failure (ALF) are imperfect, though The Kings College Criteria (KCC) are the most commonly applied tools for this purpose. Their performance in identification of patients with non paracetamol-induced ALF (non-POD ALF), who would not survive without ELT, has recently been questioned. Using quantitative techniques, we therefore performed a meta-analysis of outcome data of the KCC for prediction of survival in non-POD ALF. METHODS: A systematic database search was performed and retrieved articles graded according to a pre-agreed pro-forma of methodological quality. Collated data was meta-analysed for summary sensitivity, specificity, diagnostic odds ratio (DOR) and ROC curve analysis. Pre-specified sub-group analysis was performed on the basis of methodological quality, the severity of hepatic encephalopathy (HE) of reported patients, timing of KCC application and exclusion of those who underwent ELT. RESULTS: Eighteen studies with data on 1105 patients were available for production of 2x2 tables. Summary sensitivity was 68 (95% CI 59-77)%, specificity 82 (75-88)% and DOR 12.6 (6.5-26.1). Heterogeneity was detected in the DOR and related to methodological quality (I(2)=64% for all studies versus 47% for 'good' quality studies) and was lower in studies considering high grade HE or dynamic application of KCC (I(2)=0%). For data where ELT were excluded (13 studies) summary sensitivity was 68 (57-79)%, specificity 81 (72-90)% and DOR 12.2 (4.9-30.1) and a symmetric summary ROC curve was produced. Specificity was highest in studies of patients with high grade HE (93 (80-100)%) and where KCC were applied dynamically through the clinical course (88 (78-97)%). Sensitivity was reduced in studies published post 2005 compared with studies pre 1995 (58 (46-71)% versus 85 (76-82)%). CONCLUSIONS: KCC for outcome in non-POD ALF have good specificity and more limited sensitivity. There is significant heterogeneity in the published data partially related to methodological quality. KCC perform best in groups with high grade encephalopathy and in historically earlier studies suggesting modern medical management of ALF may modify performance of KCC. PMID- 20580461 TI - Interleukin-4 induced interferon regulatory factor (Irf) 4 participates in the regulation of alternative macrophage priming. AB - Interleukin (IL)-4 is a central regulator of T helper 2 (Th2) immune responses, and also has a major impact on innate immune cells. This cytokine primes macrophages for immune responses to parasites and induces a distinct macrophage phenotype that may also promote tissue repair. IL-4 signaling in macrophages is primarily mediated by the transcription factor signal transducer and activator of transcription 6 (Stat6), which in turn regulates a number of secondary DNA binding proteins that may participate in shaping the resulting phenotype. The impact of secondary transcription factors on IL-4-treated macrophages, however, is largely unknown. Here we show that interferon regulatory factor 4 (Irf4) is strongly induced on RNA and protein level in bone marrow-derived macrophages upon priming with IL-4. Using microarray-based whole genome expression analysis, we also demonstrate that a subset of IL-4 regulated genes, including several MHC-II genes, Ciita, Cyp1b1, and Il1rn, are dysregulated in Irf4-deficient macrophages. The presented data suggests a non-redundant role for Irf4 in shaping the phenotype of alternatively primed macrophages. PMID- 20580462 TI - Molecular characterization of a crustin-like antimicrobial peptide in the giant tiger shrimp, Penaeus monodon, and its expression profile in response to various immunostimulants and challenge with WSSV. AB - A crustin-like antimicrobial peptide from the haemocytes of giant tiger shrimp, Penaeus monodon was partially characterized at the molecular level and phylogenetic analysis was performed. The partial coding sequence of 299 bp and 91 deduced amino acid residues possessed conserved cysteine residues characteristic of the shrimp crustins. Phylogenetic tree and sequence comparison clearly confirmed divergence of this crustin-like AMP from other shrimp crustins. The differential expression of the crustin-like AMP in P. monodon in response to the administration of various immunostimulants viz., two marine yeasts (Candida haemulonii S27 and Candida sake S165) and two beta-glucan isolates (extracted from C. haemulonii S27 and C. sake S165) were noted during the study. Responses to the application of two gram-positive probiotic bacteria (Bacillus MCCB101 and Micrococcus MCCB104) were also observed. The immune profile was recorded pre- and post-challenge white spot syndrome virus (WSSV) by semi-quantitative RT-PCR. Expressions of seven WSSV genes were also observed for studying the intensity of viral infection in the experimental animals. The crustin-like AMP was found to be constitutively expressed in the animal and a significant down-regulation could be noted post-challenge WSSV. Remarkable down-regulation of the gene was observed in the immunostimulant fed animals pre-challenge followed by a significant up regulation post-challenge WSSV. Tissue-wise expression of crustin-like AMP on administration of C. haemulonii and Bacillus showed maximum transcripts in gill and intestine. The marine yeast, C. haemulonii and the probiotic bacteria, Bacillus were found to enhance the production of crustin-like AMP and confer significant protection to P. monodon against WSSV infection. PMID- 20580463 TI - Meta-analysis of lineage-specific gene expression signatures in mouse leukocyte populations. AB - In order to address fundamental questions associated with the relationships between mononuclear phagocytes and other myeloid and lymphoid cell populations, we have taken advantage of the growing body of expression data available in the public domain. We collated a large number of published expression studies on mouse haemopoietic cell lineages comprising 304 cell samples from 29 independent experiments performed on a single microarray platform (Affymetrix MOE430-2). The data were subjected to network-based cluster analysis using Biolayout Express(3D). Genes with related function clustered together in distinct regions of the graph reaffirming many known associations between gene expression and role in specific pathways and defining most major cell types of the immune system. Promoters of genes within individual clusters were distinguished by over representation of regulatory motifs recognised by specific transcription factors. However, these data indicate that commonly used myeloid subpopulation markers, such as CD11c (Itgax), do not correlate with expression of other genes, and further bring into question their use in defining myeloid cell lineage, activation (M1 vs. M2) and antigen-presenting cell function. In particular, there were few mRNA markers that clearly distinguished classical dendritic cells (DC) from macrophages, other than low expression of genes required for phagocytic activity. Bone marrow-derived DC, grown in GM-CSF, were clearly identified as phagocytes and distinguished from isolated lymphoid tissue DC. Thus, through pooling datasets from public data and examining the gene expression clusters within, we can learn a great deal about the transcriptional networks that underpin the differences in functional activities between cell populations of the immune system. PMID- 20580464 TI - Heme Oxygenase-1 expression in M-CSF-polarized M2 macrophages contributes to LPS induced IL-10 release. AB - The shift between pro-inflammatory (M1) and anti-inflammatory (M2) states of macrophage polarization allows the resolution of inflammatory processes as well as the maintenance of a basal anti-inflammatory environment in tissues continuously exposed to harmless antigens (e.g., lung and gut). To identify markers for the anti-inflammatory state of macrophages, expression profiling was performed on human macrophages polarized by either GM-CSF or M-CSF, which lead to the generation of TNF-alpha and IL-12p40-producing pro-inflammatory macrophages [M1 (GM-CSF)] or IL-10-producing anti-inflammatory macrophages [M2 (M-CSF)] upon exposure to LPS, respectively. A different iron metabolism gene signature was detected in both macrophage types, with the heme regulatory molecules CD163 and Heme Oxygenase-1 (HO-1) being preferentially expressed by M2 (M-CSF) macrophages. M1-polarizing cytokines (GM-CSF, IFNgamma) inhibited, while IL-4 enhanced, the M CSF-driven HO-1 expression. In agreement with this in vitro data, HO-1 expression in metastatic melanoma was primarily detected in CD163(+) tumor-associated macrophages, which are known to exhibit an M2-skewed polarization phenotype. In contrast to the HO-1 inhibitor tin protoporphyrin (SnPP), the administration of cobalt protoporphyrin (CoPP), a potent inducer of HO-1 resulted in increased LPS triggered IL-10 release from M2 (M-CSF) macrophages. The data suggests that HO-1 is important for the anti-inflammatory activities of M-CSF-polarized M2 macrophages. Moreover, since M2 (M-CSF) macrophages also express higher levels of the CD163 scavenger receptor, the CD163/HO-1/IL-10 axis appears to contribute to the generation of an immunosuppressive environment within the tumor stroma. PMID- 20580467 TI - Unusual extraosseous tumoral accumulation of 99mTc-MDP in non-Hodgkin's lymphoma in two cases. AB - The authors describe a rare pattern of soft tissue uptake observed in a (99m)Tc MDP bone scintigraphy of two patients with the diagnosis of non-Hodgkin's lymphoma. Both patients had abdominal masses and bone scintigraphy revealed unusual (99m)Tc-MDP uptake in the abdominal region. The possible mechanisms of soft tissue uptake of bone seeking agents are discussed. PMID- 20580465 TI - Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function. AB - To understand how microglial cell function may change with aging, various protocols have been developed to isolate microglia from the young and aged central nervous system (CNS). Here we report modification of an existing protocol that is marked by less debris contamination and improved yields and demonstrate that microglial functions are varied and dependent on age. Specifically, we found that microglia from aged mice constitutively secrete greater amounts of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) relative to microglia from younger mice and are less responsive to stimulation. Also, microglia from aged mice have reduced glutathione levels and internalize less amyloid beta peptide (Abeta) while microglia from mice of all ages do not retain the amyloid beta peptide for a significant length of time. These studies offer further support for the idea that microglial cell function changes with aging. They suggest that microglial Abeta phagocytosis results in Abeta redistribution rather than biophysical degradation in vivo and thereby provide mechanistic insight to the lack of amyloid burden elimination by parenchymal microglia in aged adults and those suffering from Alzheimer's disease. PMID- 20580468 TI - Bladder catheterization in Greek nursing education: An audit of the skills taught. AB - INTRODUCTION: The auditing of nurse teaching is in its infancy in Greece. One area urgently in need of audit is the teaching of male catheterization. AIMS: To assess the current educational model regarding male bladder catheterization at a sole tertiary education nursing establishment in a major Greek city and to improve nurse undergraduate training by implementing appropriate recommendations for change to the current educational module and support these changes in the long term. METHODS: A systematic search of international databases for guidelines or best practice regarding bladder catheterization was conducted. Audit measures included direct observation of the teaching process and compilation of a checklist. RESULTS: The shortcomings are discussed under the following headings: patient pre-preparation, choice and quality of materials used, appropriate aseptic techniques, catheter withdrawal, connecting and handling the drainage bag, diminishing risk of Catheter Associated Urinary Track Infections (CAUTIs), no problem solving trouble-shooting training, textbook and educational resources, lack of national guidelines, setting of the educational experience. CONCLUSIONS: The main problem with the teaching process exposed by the audit is entrenched use of an outmoded textbook with little effort to enrich teaching with current evidence base practices. PMID- 20580469 TI - Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice. AB - Rough mutants of Brucella abortus were generated by disruption of wbkC gene which encodes the formyltransferase enzyme involved in LPS biosynthesis. In bone marrow derived macrophages the B. abortusDeltawbkC mutants were attenuated, could not reach a replicative niche and induced higher levels of IL-12 and TNF-alpha when compared to parental smooth strains. Additionally, mutants exhibited attenuation in vivo in C57BL/6 and interferon regulatory factor-1 knockout mice. DeltawbkC mutant strains induced lower protective immunity in C56BL/6 than smooth vaccine S19 but similar to rough vaccine RB51. Finally, we demonstrated that Brucella wbkC is critical for LPS biosynthesis and full bacterial virulence. PMID- 20580470 TI - Dissection and localization of the immunostimulating domain of Edwardsiella tarda FliC. AB - Bacterial flagellin is known to induce potent immune response in vertebrate systems via the toll-like receptor (TLR) 5. As a result, flagellin has been studied extensively as a vaccine adjuvant. In a previous study, we examined the vaccine and adjuvant potentials of the flagellin (FliC) of the fish pathogen Edwardsiella tarda. We found that E. tarda FliC induced low protective immunity by itself but could function as a molecular adjuvant and potentiate the specific immune response induced by the E. tarda antigen Eta6. Since FliC is a large protein and organized into distinct structural domains, we wondered whether the immunostimulating effect observed with the full-length protein could be localized to a certain region. To investigate this question, we in the present study dissected the FliC protein into several segments according to its structural features: (i) N163, which consists of the conserved N-terminal 163 residues of FliC; (ii) M160, which consists of the variable middle 160 residues; (iii) C94, which consists of the conserved C-terminal 94 residues; (iv) NC257, which is an artificial fusion of N163 and C94. To examine the adjuvanticity of the FliC fragments, DNA vaccine plasmids expressing FliC fragments in fusion with Eta6 were constructed and used to immunize Japanese flounder. The results showed that N163 produced the best adjuvant effect, which, in respect to improvement in the relative percent survival of the vaccinated fish, was comparable to that of the full-length FliC. None of the other FliC fragments exhibited apparent immunopotentiating effect. Further analysis showed that N163 enhanced the production of serum specific antibodies and, like full-length FliC, significantly upregulated the expression of the genes that are possibly involved in innate and adaptive immunity. These results indicate that N163 is the immunodominant region of FliC and suggest that E. tarda FliC may induce immune responses in Japanese flounder via mechanisms alternative to that involving TLR5. PMID- 20580471 TI - Short and long term adaptation of variability during walking using unstable (Mbt) shoes. AB - BACKGROUND: The purpose of the study was to compare the variability of biomechanical variables during treadmill walking using unstable shoes (Masai Barefoot Technology, MBT, Roggwil, Switzerland) and conventional shoes, before and after a 10 week (wk) training period. METHODS: Cycle characteristics, plantar pressure distribution, whole body 3D kinematics, and electromyographic signals of selected leg muscles during ground contact were recorded on 12 Sport Science students while walking on a treadmill with both conventional and unstable shoes before and after a 10 wk training intervention. The intervention consisted of more than 4h use of unstable shoes during daily activity. The standard deviation of 15 consecutive cycles in each analyzed variable was taken as the measure for variability. FINDINGS: The main pattern was marked by a 35% (SD 10%) higher variability with the unstable shoes at pretest when compared with the conventional shoes, but decreased 30% (SD 12%) (both P<0.05) during the training intervention to almost equal variability in between the two shoe situations. This was especially true with regard to variables representing within gait characteristics (peak foot force, joint angles, etc.), whereas in variables describing the overall gait cycle (e.g. cycle rate, impulse of total force, etc.) no difference between MBT and conventional shoes at pre and post tests were found. INTERPRETATION: The current study supports the idea that the unstable shoe serves as a motor constraint applicable during everyday activity, provoking increased variability during walking. In addition, a decrease in movement variability on the MBT shoes during the training intervention to the level of conventional shoes was observed. PMID- 20580472 TI - Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, northern China. AB - The residue of antibiotics is becoming an intractable environmental problem in many organic vegetable bases. However, their residual levels and distribution are still obscure. This work systematically analyzed the occurrence and migration of typical veterinary antibiotics in organic vegetable bases, northern China. The results showed that there was no obvious geographical difference in antibiotic distribution between soil and manure. A simple migration model can be easy and quick to predict the accumulation of antibiotics in soil. Antibiotics were mainly taken up through water transport and passive absorption in vegetables. The distribution of antibiotics in a plant was in the sequence leaf>stem>root, and performed biological accumulation. The residues of antibiotics in all samples in winter were significantly higher than those in summer. Overall, this work can lay the foundation for understanding ecological risk of antibiotics and their potential adverse effects on human health by food chain. PMID- 20580473 TI - Use of sap flow measurements to validate stomatal functions for mature beech (Fagus sylvatica) in view of ozone uptake calculations. AB - For a quantitative estimate of the ozone effect on vegetation reliable models for ozone uptake through the stomata are needed. Because of the analogy of ozone uptake and transpiration it is possible to utilize measurements of water loss such as sap flow for quantification of ozone uptake. This technique was applied in three beech (Fagus sylvatica) stands in Switzerland. A canopy conductance was calculated from sap flow velocity and normalized to values between 0 and 1. It represents mainly stomatal conductance as the boundary layer resistance in forests is usually small. Based on this relative conductance, stomatal functions to describe the dependence on light, temperature, vapour pressure deficit and soil moisture were derived using multivariate nonlinear regression. These functions were validated by comparison with conductance values directly estimated from sap flow. The results corroborate the current flux parameterization for beech used in the DO3SE model. PMID- 20580474 TI - Dietary potassium intake and mortality in long-term hemodialysis patients. AB - BACKGROUND: Hyperkalemia has been associated with higher mortality in long-term hemodialysis (HD) patients. There are few data concerning the relationship between dietary potassium intake and outcome. STUDY DESIGN: The mortality predictability of dietary potassium intake from reported food items estimated using the Block Food Frequency Questionnaire (FFQ) at the start of the cohort was examined in a 5-year (2001-2006) cohort of 224 HD patients in Southern California using Cox proportional hazards regression. SETTING & PARTICIPANTS: 224 long-term HD patients from 8 DaVita dialysis clinics. PREDICTORS: Dietary potassium intake ranking using the Block FFQ. OUTCOMES: 5-year survival. RESULTS: HD patients with higher potassium intake had greater dietary energy, protein, and phosphorus intakes and higher predialysis serum potassium and phosphorus levels. Greater dietary potassium intake was associated with significantly increased death HRs in unadjusted models and after incremental adjustments for case-mix, nutritional factors (including 3-month averaged predialysis serum creatinine, potassium, and phosphorus levels; body mass index; normalized protein nitrogen appearance; and energy, protein, and phosphorus intake) and inflammatory marker levels. HRs for death across the 3 higher quartiles of dietary potassium intake in the fully adjusted model (compared with the lowest quartile) were 1.4 (95% CI, 0.6-3.0), 2.2 (95% CI, 0.9-5.4), and 2.4 (95% CI, 1.1-7.5), respectively (P for trend = 0.03). Restricted cubic spline analyses confirmed the incremental mortality predictability of higher potassium intake. LIMITATIONS: FFQs may underestimate individual potassium intake and should be used to rank dietary intake across the population. CONCLUSIONS: Higher dietary potassium intake is associated with increased death risk in long-term HD patients, even after adjustments for serum potassium level; dietary protein; energy, and phosphorus intake; and nutritional and inflammatory marker levels. The potential role of dietary potassium in the high mortality rate of HD patients warrants clinical trials. PMID- 20580475 TI - Renal blood flow redistribution during acute kidney injury. AB - We describe a case of acute kidney injury with decreased kidney perfusion in which contrast-enhanced computed tomography of the abdomen was performed for a nonrenal indication. This imaging procedure showed intrarenal blood flow redistribution from the cortex to the medulla that reversed after recovery of kidney function. Renal blood flow redistribution was described first almost a century ago in experimental models of renal ischemia, but clinical imaging studies are scarce. We provide a clear example of this phenomenon using contrast enhanced computed tomography. PMID- 20580476 TI - Is there any reason to stent atherosclerotic renal artery stenosis? PMID- 20580477 TI - Change in use of gadolinium-enhanced magnetic resonance studies in kidney disease patients after US Food and Drug Administration warnings: a cross-sectional study of Veterans Affairs Health Care System data from 2005-2008. AB - BACKGROUND: Exposure to gadolinium in patients with kidney disease has been linked to risk of developing nephrogenic systemic fibrosis. The US Food and Drug Administration (FDA) has issued warnings against the use of gadolinium in this population. We studied the impact of these warnings on the use of gadolinium enhanced magnetic resonance (GE-MR) studies in patients with decreased estimated glomerular filtration rate (eGFR) and the practice of measuring serum creatinine before gadolinium exposure. STUDY DESIGN: Cross-sectional study of patients who had undergone MR studies from October 2002 to September 2008. SETTING & PARTICIPANTS: Patients receiving medical care in the US Department of Veterans Affairs Health Care System. PREDICTOR: Date of MR imaging, serum creatinine level, and eGFR using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. OUTCOMES & MEASUREMENTS: The rate of MR studies performed with and without gadolinium from July 2005 to September 2008 in patients with different stages of kidney disease, defined using eGFR. The proportion of GE-MR studies with a screening serum creatinine level. RESULTS: There was a 71% decrease in the rate of GE-MR use in patients with GFR<30 mL/min/1.73 m2 2 years after the release of the first public health advisory, although studies continued to be performed in patients with stages 4 and 5 chronic kidney disease. The proportion of GE-MR studies with serum creatinine measured within 1 month before the study increased by 99%. LIMITATIONS: Data available up to September 30, 2008. Indications for the GE-MR studies were not assessed. The accuracy of Current Procedural Terminology and International Classification of Diseases, Ninth Revision coding was not assessed. CONCLUSION: There was a large decrease in the use of GE-MR studies in patients with GFR<30 mL/min/1.73 m2 and a large but not universal increase in the practice of measuring serum creatinine before GE-MR after the release of the FDA warnings. PMID- 20580478 TI - Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study. AB - BACKGROUND: Higher serum phosphorus levels are associated with cardiovascular disease (CVD) events in the general population, an association that may be stronger in men. Estradiol has phosphaturic properties. Whether higher serum phosphorus levels are associated with left ventricular (LV) mass in persons without end-stage renal disease and whether the association is modified by sex is unknown. STUDY DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: 978 outpatients with stable CVD. PREDICTOR: The primary predictor variable was serum phosphorus level. Sex was evaluated as an effect modifier. OUTCOME & MEASUREMENTS: LV mass using transthoracic echocardiography. RESULTS: The association of serum phosphorus level with LV mass differed by sex (interaction P=0.04). In models adjusted for age, race, kidney function, smoking, diabetes, blood pressure, cholesterol level, C-reactive protein level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, each 1 mg/dL higher serum phosphorus level was associated with 4.52-g/m2 greater LV mass (95% CI, 1.04-8.01; P=0.01) in men. Conversely, in women, no statistically significant association was found between serum phosphorus level and LV mass. LIMITATIONS: Older adult population with stable CVD; 19% were women. CONCLUSIONS: In outpatients with stable CVD, higher serum phosphorus levels are associated with greater LV mass in men, but not women. Whether sex hormones may account for these differences requires future study. PMID- 20580480 TI - [Sleep apnea-hypopnea syndrome in the elderly]. AB - The population pyramid is changing due to the increasing longevity of the population, making it a priority to have better knowledge of those diseases that have an increasingly major impact in advanced age. Sleep apnea-hypopnea syndrome (SAHS) affects 15-20% of individuals over 65 years. However, despite this high prevalence and that one in four sleep studies are conducted on the elderly in this country and that more 60% of these were treated with CPAP, there are few specific studies in this age group on the diagnosis and management of this syndrome. The physiological increase of the number of sleep respiratory disorders with the passing of time may be the biggest obstacle when defining, diagnosing and treating SAHS in the elderly. In any case and while more solid scientific evidence is obtained, the National SAHS Consensus, as well as the Guidelines on the diagnosis and treatment of SAHS, recommend that, within logical limits, age itself should not be an obstacle to offering the elderly diagnostic help and treatment similar to that offered to the rest of the population. PMID- 20580479 TI - Cortisol, interleukins and S100B in delirium in the elderly. AB - In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL 8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1pg/ml) and cortisol (666, 95% CI: 475 859nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microg/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker. PMID- 20580481 TI - Surgery as the treatment of choice in vulvar lymphangioma circumscriptum: case report and review of other management options. PMID- 20580482 TI - Modelling of multi-component immunoassay kinetics - A new node-based method for simulation of complex assays. AB - The behaviour of binding reactions in immunoassays can be predicted and studied by modelling methods. Simple antibody-analyte binding reaction kinetics can be simulated by e.g. a mechanistic assay model based on differential equations. However, the mathematical modelling becomes more complicated if multivalent structured components are involved and the number of binding complexes increases. In this paper, a new node-based method to model complex binding reactions is introduced. The principle of this method is to construct a network of the initial components, reaction intermediates and end-products by forming a network of nodes. This network is then solved, node by node, breaking the initial problem into smaller partial problems, still obeying the laws of chemical reaction kinetics and without ignoring any parts of the problem. This method provides an easy and quick way to study complex binding reactions since simulation networks are simple to construct directly from the reaction scheme. This presented new "NODE"-method is compared with the well known mechanistic assay model. PMID- 20580483 TI - Prostate cancer prevention trial and European randomized study of screening for prostate cancer risk calculators: a performance comparison in a contemporary screened cohort. AB - BACKGROUND: Several models can predict the risk of prostate cancer (PCa) on biopsy. OBJECTIVE: To evaluate the performance of the Prostate Cancer Prevention Trial (PCPT) and European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators in detecting PCa in a contemporary screened cohort. DESIGN, SETTING, AND PARTICIPANTS: We analyzed prebiopsy characteristics of 525 consecutive screened patients submitted to biopsy, as required by the risk calculators, in one European center between 2006 and 2007. MEASUREMENTS: Comparisons were done using tests of accuracy (area under the receiver operating characteristic curve [AUC-ROC]), calibration plots, and decision curve analysis. Biopsy predictors were identified by univariate and multivariate logistic regression. RESULTS AND LIMITATIONS: PCa was detected in 35.2% of the subjects. Among predictors included in the calculators, the logarithmic transformations of prostate volume and prostate-specific antigen (PSA), digital rectal examination, previous biopsy status, and age were significantly associated with PCa; transrectal ultrasound abnormalities and family history were not. AUC-ROC for the ERSPC calculator was significantly higher than the PCPT calculator and PSA alone (80.1%, 74.4%, and 64.3%, respectively). Calibration plots showed better performance for the ERSPC calculator; nevertheless, ERSPC may underestimate risk, while PCPT tends to overestimate predictions. Decision curve analysis displayed higher net benefit for the ERSPC calculator; 9% and 23% unnecessary biopsies can be avoided if a threshold probability of 20% and 30%, respectively, is adopted. In contrast, the PCPT model displayed very limited benefit. Our findings apply to a screened European cohort submitted to extended biopsy schemes; consequently, caution should be exerted when considering different populations. CONCLUSIONS: The ERSPC risk calculator, by incorporating several risks factors, can aid in the estimation of individual PCa risk and in the decision to perform biopsy. The ERSPC calculator outperformed the PCPT model, which is of very limited value, in a contemporary cohort of screened patients. PMID- 20580484 TI - Docetaxel rechallenge in castration-resistant prostate cancer: scientific legitimacy of common clinical practice. PMID- 20580485 TI - Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients. AB - BACKGROUND: The role of laparoscopic adrenalectomy in the treatment of patients with adrenocortical carcinoma (ACC) is controversial. OBJECTIVE: Our aim was to compare oncologic outcome in patients with ACC who underwent either open adrenalectomy (OA) or laparoscopic adrenalectomy (LA) for localised disease. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of 152 patients with stage I-III ACC with a tumour < or =10 cm registered with the German ACC Registry. INTERVENTION: Patients were stratified into two groups according to the surgical procedure (LA or OA). For comparison, we used both a matched pairs approach by selecting for each patient from the LA group (n=35) one corresponding patient from the OA group (n=117) and multivariate analysis in all 152 patients. MEASUREMENTS: Disease-specific survival was chosen as the predefined primary end point. Secondary end points were recurrence-free survival, frequency of tumour capsule violation and postoperative peritoneal carcinomatosis, and incidence and reasons for conversion from LA to OA. RESULTS AND LIMITATIONS: LA and OA did not differ with regard to the primary end point using either the matched pairs approach (hazard ratio [HR] for death: 0.79; 95% confidence interval [CI], 0.36-1.72; p=0.55) or multivariate analysis (HR for death: 0.98; 95% CI, 0.51-1.92; p=0.92). Similarly, adjusted recurrence-free survival was not different between LA and OA (HR: 0.91; 95% CI, 0.56-1.47; p=0.69). Frequency of tumour capsule violation and peritoneal carcinomatosis were comparable between groups. In 12 of 35 patients of the LA group, surgery was converted to open surgery with no impact on the clinical outcome. CONCLUSIONS: For localised ACC with a diameter of < or =10 cm, LA by an experienced surgeon is not inferior to OA with regard to oncologic outcome. PMID- 20580486 TI - Traumatic cervical artery dissection in head injury: the value of follow-up brain imaging. AB - INTRODUCTION: Traumatic cervical artery dissection (TCAD) is a relative infrequent complication of traumatic brain injury (TBI). Since TCAD is associated with morbidity in a considerable percentage of patients, it is important to obtain clues for recognising TCAD in this category of patients. METHODS: Retrospective case-cohort study in severe TBI patients. RESULTS: Five patients with traumatic cervical artery dissection after severe TBI, leading to ischemic strokes, are described. Secondary deterioration to coma was present in four out of five patients during admission. The diagnosis of TCAD was delayed in most cases because the secondary deterioration was often attributed to multisystem problems related to trauma patients, i.e. shock or hypoxia or medication effects. Local clinical symptoms and signs suggestive of TCAD are difficult to detect in this patient group. In all patients, the CT-scan on admission demonstrated no abnormalities. A follow-up scan at day 2 revealed that in all patients abnormalities in the vascular territories had evolved. CONCLUSION: With this case cohort study we underline the importance of considering TCAD in severe TBI patients and emphasise the role for standard follow-up brain imaging. Also possible treatment consequences are discussed. PMID- 20580487 TI - The anti-tumor agent, p-DDAP potently suppresses proliferation through apoptosis in human neuroblastoma NB-39-nu cells. AB - Retinoic acid (RA) is a chemotherapeutic agent used to induce neuronal cellular differentiation of neuroblastoma. However, because treatment with RA is associated with the side-effect of nyctalopia, efforts have been underway to identify new compounds that could potentially overcome these drawbacks. As part of these studies we have examined anti-cancer effects on the neuroblastoma NB-39 nu cells of p-dodecylaminophenol (p-DDAP), a novel derivative of N-(4 hydroxyphenyl) retinamide (4-HPR). p-DDAP suppresses proliferation, and induces G(0)/G(1) arrest and apoptosis to a greater extent than RA and 4-HPR. Neuronal differentiation was not detected in p-DDAP-treated cells. Since p-DDAP is not toxic and does not reduce blood retinol levels, p-DDAP might be a useful anti neuroblastoma drug having reduced side-effects. PMID- 20580488 TI - Role of hydroxyl radical during electrolytic degradation of contaminants. AB - The role of hydroxyl radical is investigated in electrochemical oxidation of organic contaminants with naphthalene as a model compound. The strategy employed was competitive kinetic for hydroxyl radical between naphthalene and other hydroxyl scavengers if the hydroxyl radical is produced in situ at the anode by the electrolysis of water. Methanol, d3-methanol, acetone and d6-acetone were used as competitors for hydroxyl radical and their molar concentrations were calculated based on their reaction constants with hydroxyl radical. The hydroxyl radical was not responsible for naphthalene loss in these experiments. The first order reaction rate constants in the batch experiments containing only naphthalene, 2 mM of each of acetone and d6-acetone were 0.093, 0.094 and 0.118 h(-1), respectively. Higher concentrations (4 mM) acetone and d6-acetone did not affect naphthalene degradation. Rate constants using methanol and d6-methanol as competitors for hydroxyl radical in batch degradations test were 0.128 and 0.099 h(-1), respectively. Based on the naphthalene degradation trends and reaction rate constants, it was concluded that, under the given set of conditions, hydroxyl radical was not responsible for naphthalene degradation during electrolytic degradation tests. This research suggests that the role of hydroxyl radical should be considered very carefully in modeling such indirect electrolytic oxidation processes. PMID- 20580489 TI - Synthesis of Ag/ZnO nanorods array with enhanced photocatalytic performance. AB - Silver-modified ZnO nanorods array has been prepared and the effect of silver modification has been studied. ZnO nanorods array were fabricated through a wet chemical route and a photo deposition method was taken to fabricate silver nano particulate on the ZnO nanorods. The structural and optical properties were characterized by field emission scanning electron microscope, high resolution transmission electron microscope, X-ray photoelectron spectroscopy, Raman, UV-vis and photoluminescence (PL) spectra. The UV photocatalytic activity of these materials was studied by analyzing the degradation of methylene blue (MB) in aqueous solution. The photocatalytic performance indicated that Ag deposit acted as not only electron sinks to enhance the separation of photoexcited electrons from holes, but also charge carrier recombination centers, so the optimized amount of Ag deposit was investigated. PMID- 20580490 TI - Nitrogen-doped TiO2 modified with NH4F for efficient photocatalytic degradation of formaldehyde under blue light-emitting diodes. AB - A nitrogen-doped TiO(2) (N-TiO(2)) photocatalyst was prepared by calcination of the hydrolysis precipitate of Ti(SO(4))(2) with aqueous ammonia. The prepared N TiO(2) was treated with NH(4)F (F-N-TiO(2)) by an impregnation-calcination method. The photocatalyst (F-N-TiO(2)) was characterized by X-ray diffraction (XRD), Fourier Transform Infrared (FT-IR), UV-vis diffusive reflectance spectroscopy (DRS), BET and X-ray photoelectron spectroscopy (XPS). With blue light-emitting diode (LED) as the light source, its photocatalytic activity for the degradation of formaldehyde was investigated. NH(4)F treatment enhances markedly photocatalytic activity of N-TiO(2). The treatment increases the visible absorption of N-TiO(2), decreases its specific surface area and influences the concentration of oxygen vacancies in N-TiO(2). Photocatalytic activity of F-N TiO(2) depends on the visible absorption, the specific surface area, and the concentration of oxygen vacancies. The preparation conditions, such as the calcination temperature and the initial molar ratio of NH(4)F to N-TiO(2), have a significant influence on the photocatalytic activity. The doping mechanism of NH(4)F was investigated. PMID- 20580491 TI - Stabilized sanitary landfill leachate treatment using anionic resin: treatment optimization by response surface methodology. AB - The treatability of stabilized sanitary landfill leachate via synthetic anion exchange resin (INDION FFIP MB) was investigated. An ideal experimental design was conducted based on central composite design using a response surface methodology to assess individual and interactive effects of critical operational variables (i.e., anionic dosage; contact time; shaking speed) and pH on treatment performance in terms of color, chemical oxygen demand (COD), suspended solid (SS), and turbidity removal efficiencies. Optimum operational conditions were established as 30.9 cm(3) anionic dosage, 90 min contact time, 150 rpm shaking speed, and pH 3.1. Under these conditions, the color, COD, SS, and turbidity removal efficiencies of 91.5, 70.3, 93.1, and 92.4% were experimentally attained and were found to fit well with the prediction model. According to these results, stabilized leachate treatment using INDION FFIP MB could be an effective alternative in the administration of color, COD, SS, and turbidity problems of landfill leachates. PMID- 20580492 TI - Low salivary cortisol levels in infants of families with an anthroposophic lifestyle. AB - The anthroposophic lifestyle implies environmental conditions for the infant aimed at reducing negative stress stimulation and is also related to a lower prevalence of allergic diseases in children. One aim of this prospective birth cohort study was to assess stress levels in infants with an anthroposophic lifestyle. A total of 330 infants from families with anthroposophic or more conventional lifestyles were followed from pregnancy of their mothers until the age of 6 months. Information on lifestyle factors was obtained from questionnaires. Salivary samples from 210 6-month olds and their parents were collected on three occasions during 1 day for analysis of cortisol. Infants from families with an anthroposophic lifestyle had significantly lower cortisol levels on all three sampling occasions compared to other infants. In the morning, the geometric means of salivary cortisol concentration (with 95% confidence limits) were 8.8 nmol/l (6.7-11.5), 11.3 nmol/l (9.3-13.7) and 14.9 nmol/l (11.3-19.6) in infants classified as anthroposophic, partly anthroposophic and non anthroposophic, respectively (p=0.018). On the other hand, there was no difference in cortisol levels between the parents in the different groups. Several lifestyle factors differed significantly between the groups, but none of them independently explained the difference in cortisol levels. However, living on a farm during pregnancy was significantly associated with low saliva cortisol level in the infant. It can be concluded that low salivary cortisol levels in infants from anthroposophic families may be related to an environment with a lower degree of exposure to stress, which could influence the development of allergic diseases. PMID- 20580493 TI - Effect of starter culture and fermentation temperature on water mobility and distribution in fermented sausages and correlation to microbial safety studied by nuclear magnetic resonance relaxometry. AB - Water mobility and distribution in fermented sausages produced with differences in pH development as a result of the use of three different starter cultures (T SPX, F-1, or F-SC-111) and two fermentation temperatures (24 degrees C, or 32 degrees C) were studied using low-field proton NMR relaxometry. Changes in the distribution and mobility of water in fermented sausages upon fermentation and drying were detectable by NMR T(2) relaxation, and the progress in the drying process could be followed as a shift towards faster relaxation times. In addition, the distribution of water in the sausages was significantly affected by the pH decline. The sausages were spiked with Listeria monocytogenes, Salmonella, and Escherichia coli VTEC, and partial least squares regressions revealed that 90% of the variation in reduction of Salmonella and VTEC could be explained by the NMR T(2) relaxation decay. Consequently, the study demonstrated that NMR relaxometry is a promising technique for elucidating process parameters and microbial safety in the production of fermented meat products. PMID- 20580494 TI - The effects of method of castration, rearing condition and diet on sensory quality of pork assessed by a trained panel. AB - Beside surgical castration possible alternatives helping to reduce the incidence of boar taint in cooked pork are rearing conditions, immunocastration and feeding strategies for entire males known to lower the skatole levels. The goal of this study was to assess the effects of these alternatives on the sensory acceptability of pork. In experiment 1, carcasses from barrows, entire males (EM) and entire males fed raw potato starch (EM+) 7d before slaughter were selected based on the androstenone (0.05), boar odour and flavour scores were greater (P<0.05) in EM+ than barrows. In experiment 2, scores for boar odour and flavour were lower (P<0.05) in pork from barrows and IC than EMP, with intermediate values for EMG. In conclusion, we observed a discrepancy between the known boar taint compounds androstenone and skatole and sensory acceptability, which indicates that other factors influenced the perception of boar taint. Thus, surgical castration with or without anesthesia or immunocastration are still the safest methods to avoid boar taint. PMID- 20580495 TI - Risk-taking but not response inhibition or delay discounting predict alcohol consumption in social drinkers. AB - Impulsivity and risk-taking are multi-dimensional constructs that have been implicated in heavy drinking and alcohol problems. Our aim was to identify the specific component of impulsivity or risk-taking that explained the greatest variance in heavy and problem drinking among a sample of young adults recruited from a university population. Participants (N=75) completed a test battery comprising two commonly used response inhibition tasks (a Go/No-Go task and a Stop signal task), a delay discounting procedure, and the Balloon Analogue Risk Task (BART) as a measure of risk-taking. Participants also completed the Barratt Impulsivity Scales (BIS) as a measure of trait impulsivity. In a hierarchical multiple regression model, risk-taking was identified as the only behavioural measure that predicted alcohol use and problems. In a secondary analysis, we demonstrated that risk-taking predicted unique variance in alcohol use and problems over and above that explained by trait impulsivity. Results suggest that among young adults, a behavioural measure of risk-taking predicts variance in alcohol consumption and alcohol problems, even when individual differences in trait impulsivity are statistically controlled. However, behavioural measures of response inhibition and delay discounting do not predict unique variance in alcohol use in young adult social drinkers. PMID- 20580496 TI - Variable Number Tandem Repeat (VNTR) analysis reveals genetic diversity within Mycoplasma mycoides mycoides small colony isolates from Nigeria. AB - A Variable Number Tandem Repeat (VNTR) analysis was conducted on thirteen (13) M. mycoides mycoides Small Colony isolates from Nigeria using Tandem Repeat (TR) 34 which is a predicted lipoprotein located within the hypothetical protein MAG6170. The analysis revealed diversity within the M. mycoides mycoides Small Colony isolates with five different VNTR types indicated. Some correlation was determined between the VNTR types and their geographical origin. VNTR analysis may represent a useful, rapid first-line test for use in molecular epidemiological analysis of M. mycoides mycoides Small Colony for possible outbreak tracing and disease control. PMID- 20580497 TI - Genetic analyses of H5N1 avian influenza virus in Mongolia, 2009 and its relationship with those of eastern Asia. AB - In May and August 2009, 14 highly pathogenic H5N1 isolates were obtained from migratory birds in central Mongolia. To trace the genetic lineage of the isolates, nucleotide sequences of all eight genes were determined and phylogenetically analyzed. Hemagglutinin and nucleoprotein genes were clustered in clade 2.3.2. The polymerase acidic gene was related to the isolates of South Korea and Japan obtained in 2003 and 2004 outbreaks, and a migratory duck isolate from Jiangxi, China. The neuraminidase and other internal genes were closely related to those of clade 2.3.4 viruses. The results indicate evolving genetic diversity of the hemagglutinin gene and acquisition of different polymerase acidic gene in the 2009 Mongolian isolates, likely via bird migration. Prevention of potentially wider outbreak in domestic poultry and accurate monitoring of H5N1 genetic mutation will require continuous monitoring for H5N1 in both domestic and wild birds, and will necessitate international cooperation with neighboring countries sharing migratory flyways. PMID- 20580498 TI - Pseudo-membranes on internal organs associated with Rhodococcus qingshengii infection in Atlantic salmon (Salmo salar). AB - This paper describes a pathological condition in intensive reared Atlantic salmon (Salmo salar), restricted to the appearance of pseudo-membranes covering internal organs (i.e. spleen, liver, heart and others) associated with the presence of large numbers of a Gram-positive bacteria. Isolate 79043-3, obtained as pure culture from affected fish, was subjected to a polyphasic taxonomic study in order to determine its exact taxonomic position, as well as to experimental challenges leading to determine its pathogenic potential for cultured fish. Based on this characterization, we report the first isolation of Rhodococcus qingshengii, from a farmed population of Atlantic salmon in Chile. Virulence studies demonstrated that the isolate fulfilled the Koch's postulates, suggesting that this bacterial species could be considered as an opportunistic pathogen for Atlantic salmon. PMID- 20580500 TI - A review of select vitamins and minerals used by postmenopausal women. AB - OBJECTIVES: The purpose of this review is to summarize the effectiveness of select vitamins, minerals and trace elements in postmenopausal women for their effects on bone health, cardiovascular health, breast cancer, cognition and vasomotor symptoms. METHODS: Review of the relevant literature and results from recent clinical studies, as well as critical analyses of published systematic reviews and meta-analyses were obtained from PubMed and Cochrane Library of Reviews. Vitamin A, the B vitamins, vitamin C, calcium, vitamin D, vitamin E, vitamin K, magnesium, selenium and zinc were selected for review. In circumstances where the vitamin, mineral or trace element has not been studied for a given condition, no information was provided. RESULTS AND DISCUSSION: All vitamins, minerals and trace elements play an important role in maintaining health and wellbeing among menopausal women. Adequate dietary intake is essential and supplementation should be considered in women with documented malabsorption syndromes or deficiencies. Based on a review of the literature, supplementation with vitamin C, D, K and calcium can also be recommended for proper maintenance of bone health. The only supplement studied for vasomotor symptoms was vitamin E and this vitamin lacked clinical support. Supplementation in healthy postmenopausal women with vitamins and minerals in diet or pill forms cannot be recommended currently for any other indications. PMID- 20580499 TI - Parental body size and early weight and height growth velocities in their offspring. AB - BACKGROUND: Whereas weight or height at a given age are the results of the cumulative growth experience, growth velocities allows the study of factors affecting growth at given ages. AIM: To study the relationships between parental height and body mass index (BMI) and offspring's height and weight growth during infancy and childhood. STUDY DESIGN: From the FLVSII population-based study, 235 parent-child trios belonging to 162 families examined in 1999. OUTCOME MEASURES: From medical records and previous FLVS examinations, child's height and weight history were reconstructed. Weight and height growth velocities from birth to seven years were estimated from a modelling of individual growth curve and correlated with parent's body size in 1999. RESULTS: Ponderal index and length at birth were significantly associated with maternal but not paternal BMI and height. In the first six months, height growth velocity was significantly associated with maternal stature (at three months: 0.12+/-0.05 and 0.02+/-0.05 cm/month for a 10 cm difference in maternal and paternal height respectively) and weight growth velocity with paternal BMI (at three months: 5.7+/-2.8 and 1.9+/ 2.3g/month for a difference of 1 kg/m(2) in paternal and maternal BMI respectively). Between two and five years, height growth velocity was more significantly associated with paternal height whereas weight growth velocity was more closely associated with maternal BMI. CONCLUSIONS: Early childhood growth is characterised by alternate periods associated specifically with maternal or paternal BMI and height. This novel finding should trigger the search for specific genetic, epigenetic or environmentally shared factors from the mothers and fathers. PMID- 20580501 TI - Alternative and complementary therapies for the menopause. AB - The use of complementary and alternative medicine (CAM) among menopausal women has increased in the last years. This review examines the evidence from systematic reviews, RCTs and epidemiological studies of CAM in the treatment of menopausal symptoms. Some evidence exists in favour of phytosterols and phytostanols for diminishing LDL and total cholesterol in postmenopausal women. Similarly, regular fiber intake is effective in reducing serum total cholesterol in hypercholesterolemic postmenopausal women. Clinical evidence also exists on the effectiveness of vitamin K, a combination of calcium and vitamin D or a combination of walking with other weight-bearing exercise in reducing bone mineral density loss and the incidence of fractures in postmenopausal women. Black cohosh appears to be effective therapy for relieving menopausal symptoms, primarily hot flashes, in early menopause. Phytoestrogen extracts, including isoflavones and lignans, appear to have only minimal effect on hot flashes but have other positive health effects, e.g. on plasma lipid levels and bone loss. For other commonly used CAMs, e.g. probiotics, prebiotics, acupuncture, homeopathy and DHEA-S, randomized, placebo-controlled trials are scarce and the evidence is unconvincing. More and better RCTs testing the effectiveness of these treatments are needed. PMID- 20580502 TI - SERMs: progress and future perspectives. AB - Selective estrogen receptor modulators (SERMs) interact with estrogen receptors as agonists or antagonists depending on the target tissue. Currently available SERMs are used to treat and prevent breast cancer and osteoporosis, to treat ovulatory dysfunction in women, and for contraception. Because current therapies do not adequately treat menopausal symptoms, the search continues for the optimal SERM for postmenopausal women, which would relieve hot flushes, treat vaginal atrophy, and prevent fractures, while protecting the endometrium, breast, and cardiovascular system. Future use of SERMs may also include their use in a tissue selective estrogen complex (TSEC), a therapy that combines a SERM with estrogen(s), designed to deliver the efficacy of each component with improved overall tolerability for the treatment of postmenopausal women. The future of SERMs may also include their use in men for the treatment of osteoporosis and various syndromes associated with secondary hypogonadism and possibly prostate cancer. Continued research should allow the full potential of SERMs to be uncovered. PMID- 20580503 TI - Combined diffusion-weighted and dynamic contrast-enhanced imaging of patients with acute osteoporotic vertebral fractures. AB - OBJECTIVES: To evaluate the potential and to analyze parameter correlations of combined quantitative diffusion-weighted MRI (DWI) and high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) in vertebral bone marrow (vBM) of patients with osteoporosis and acute vertebral compression fractures, providing additional information for a better understanding of the physiological background of parameter changes. MATERIALS AND METHODS: 20 patients with acute osteoporotic fractures were examined with DWI and DCE-MRI at 1.5 T. DCE-MRI was performed with a 2D saturation-recovery turbo-FLASH sequence, acquiring 300 dynamics with a temporal resolution of 1 s. For DWI measurements, a DW HASTE sequence with b values from 100 to 600 s/mm2 was applied. In each patient, ROIs were drawn manually in the fractures and in normal appearing vertebrae. For DCE-MRI, the concentration-time curves of these ROIs were analyzed using a two-compartment tracer-kinetic model in the lesions, providing separate estimates of perfusion and permeability, and a one-compartment model in normal vBM, providing only a mixed representation of perfusion and permeability in terms of a mixed flow parameter K(trans) and the extracellular volume (ECV). In the case of DWI, attenuation curves were fitted to a monoexponential decay model to determine the apparent diffusion coefficient (ADC). RESULTS: Mean perfusion parameters and ADCs were significantly (p<0.001) different in the fractures compared to adjacent normal appearing vertebrae (K(trans): 7.81 mL/100 mL/min vs. 14.61 mL/100 mL/min, ECV: 52.84 mL/100 mL vs. 4.61 mL/100 mL, ADC: 1.71*10-3 mm2/s vs. 0.57*10-3 mm2/s). ADCs showed a significant correlation with the ECV. CONCLUSION: The quantitative analysis of DWI and DCE-MRI could distinguish osteoporotic fractures from normal appearing vertebrae. A significant correlation found between ECV and ADCs might be able to explain the cause for the increased diffusivity in osteoporotic fractures. Since the other perfusion parameters do not correlate with the ADC, they provide additional pathophysiological information not accessible with DWI. PMID- 20580504 TI - Use of foetal MRI in diagnosing hepatic hemangioendotheliomas: a report of four cases. AB - OBJECTIVE: To examine the appearance of foetal hepatic hemangioendotheliomas using prenatal magnetic resonance imaging (MRI) and to conclude whether MRI provides additional information to that obtained with ultrasonography (US). MATERIALS AND METHODS: Four foetuses with hepatic hemangioendotheliomas were evaluated by US and MRI between 2005 and 2008. MRI was performed on four foetuses at 33+4, 37+4, 24 and 21+6 weeks gestation following US evaluations that demonstrated foetal abdominal tumours. The prenatal US and MRI findings were compared with the postnatal physical examination, enhancement computed tomography (CT) and serial ultrasound examinations, or with the pathology exams, retrospectively. RESULTS: All four foetuses showed very similar prenatal MRI findings. In each case, the foetal MRI detected an isolated vascular hepatic tumour with low T1 and inhomogeneous high T2 signal intensity. In one case, multiple scalp hemangiomas were detected in the postnatal physical examination, but not with the prenatal US and MRI exams. In the other three cases, the prenatal US and MRI findings were in complete agreement with the postnatal diagnoses. CONCLUSION: Prenatal MRI is effective in the assessment of foetal hepatic hemangioendotheliomas. Prenatal MRI may provide a useful adjunct to US in assessing foetal hepatic tumours. PMID- 20580505 TI - Role of PROPELLER diffusion-weighted imaging and apparent diffusion coefficient in the evaluation of pituitary adenomas. AB - OBJECTIVE: The relationship between tumor consistency and apparent diffusion coefficient (ADC) values is controversial. We evaluated the role of the ADC using an advanced diffusion-weighted imaging (DWI) technique. We employed periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DWI acquired on a 3-T magnetic resonance imaging (MRI) scanner to assess the consistency of pituitary adenomas and examined the relationship between the ADC and the hormone secretion status of the tumors and their MIB-1 labeling index (MIB-1 LI). MATERIALS AND METHODS: The study protocol was approved by our institutional review board. We retrospectively studied 24 operated patients with pituitary adenomas who had undergone PROPELLER DWI on a 3-T MRI scanner. Conventional MRI findings were expressed as the ratio of the signal intensity (SI) in the lesions to the SI of the normal white matter and the degree of contrast enhancement. Minimum-, mean-, and maximum ADC (ADCmin, ADCmean, ADCmax) values were calculated. The consistency of the tumors was determined by neurosurgeons. All surgical specimens were submitted for histological study to calculate the MIB-1 LI and the percent collagen content. Preoperative MRI-, intraoperative-, and histological findings were analyzed by a statistician. RESULTS: Our study included 15 soft-, 5 fibrous-, and 4 hard tumors. Tumor consistency was strongly associated with the percent collagen content. However, neither the tumor consistency nor the percent collagen content was correlated with MRI findings or ADC values. The SI of growth hormone-producing adenomas on T2-WI was lower than of the other pituitary adenomas studied (p<0.01); no other significant difference was found in the ADC or on conventional MRI between pituitary adenomas with different secretory functions. The MIB-1 LI of pituitary adenomas was not correlated with their appearance on conventional MRI or their ADC values. CONCLUSION: Using the PROPELLER DWI technique we confirmed that the ADC was not correlated with the consistency of pituitary adenomas. We also demonstrate that the ADC was not associated with the hormone-secreting status or the MIB-1 LI of pituitary adenomas. PMID- 20580506 TI - Detection of biliary stenoses in patients after liver transplantation: is there a different diagnostic accuracy of MRCP depending on the type of biliary anastomosis? AB - PURPOSE: Two different forms of biliary anastomosis can be created in patients undergoing liver transplantation: (a) bilio-digestive anastomoses or (b) choledocho-choledochostomy. Aim of this study was to assess the accuracy of MR cholangiopancreatography (MRCP) for the depiction of biliary stenoses in liver transplant patients depending on the type of biliary anastomosis. METHOD AND MATERIALS: 24 liver transplant patients with clinical suspicion of biliary stenosis were studied (each 12 with bilio-digestive anastomosis/choledocho choledochostomy). MRCP was performed on a 1.5 T scanner (Magnetom Avanto, Siemens) including 2D single shot RARE, 2D T2w HASTE, TrueFISP and 3D high resolution navigator corrected sequences. Presence of (a) anastomotic stenoses (AST) and (b) NAS (non-anastomotic strictures) were assessed. Percutaneous transhepatic cholangiography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP) were performed within 48h after MRCP and served as the standard of reference. RESULTS: In patients with bilio-digestive anastomoses sensitivities of MRCP for the detection of AST and NAS amounted to 50% and 67%, respectively with specificity values of 83% and 50%. In patients with choledocho-chledochostomy sensitivities (AST: 100%, NAS: 100%) and specificities (AST: 100%, NAS: 88%) were significantly higher. CONCLUSION: Biliary strictures after liver transplantation can be accurately detected by MRCP in patients after choledocho-chledochostomy. However, the diagnostic value of MRCP is lower if liver transplantation was performed in combination with a bilio digestive anastomosis. This may be due to the less exact depiction of the anastomosis in the bowel wall. Thus, it is crucial to know the type of biliary anastomosis before choosing a diagnostic procedure. PMID- 20580507 TI - Analysis of Actinobacteria from mould-colonized water damaged building material. AB - Mould-colonized water damaged building materials are frequently co-colonized by actinomycetes. Here, we report the results of the analyses of Actinobacteria on different wall materials from water damaged buildings obtained by both cultivation-dependent and cultivation-independent methods. Actinobacteria were detected in all but one of the investigated materials by both methods. The detected concentrations of Actinobacteria ranged between 1.8 x 10(4) and 7.6 x 10(7) CFUg(-1) of investigated material. A total of 265 isolates from 17 materials could be assigned to 31 different genera of the class Actinobacteria on the basis of 16S rRNA gene sequence analyses. On the basis of the cultivation independent approach, 16S rRNA gene inserts of 800 clones (50%) were assigned to 47 different genera. Representatives of the genera Streptomyces, Amycolatopsis, Nocardiopsis, Saccharopolyspora, Promicromonospora, and Pseudonocardia were found most frequently. The results derived from both methods indicated a high abundance and variety of Actinobacteria in water damaged buildings. Four bioaerosol samples were investigated by the cultivation-based approach in order to compare the communities of Actinobacteria in building material and associated air samples. A comparison of the detected genera of bioaerosol samples with those directly obtained from material samples resulted in a congruent finding of 9 of the overall 35 detected genera (25%), whereas four genera were only detected in bioaerosol samples. PMID- 20580508 TI - Online identification of the antioxidant constituents of traditional Chinese medicine formula Chaihu-Shu-Gan-San by LC-LTQ-Orbitrap mass spectrometry and microplate spectrophotometer. AB - Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula containing seven herbal medicines, has been used in treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression clinically. However, the chemical constituents in CSGS had not been studied so far. To quickly identify the chemical constituents of CSGS and to understand the chemical profiles related to antioxidant activity of CSGS, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry has been applied for online identification of chemical constituents in complex system, meanwhile, antioxidant profile of CSGS was investigated by the fraction collecting and microplate reading system. As a result, 33 chemical constituents in CSGS were identified. Among them, 13 components could be detected both in positive and in negative ion modes, 20 constituents were determined only in positive ion mode and 2 components were only detected in negative ion mode. Meanwhile, the potential antioxidant profile of CSGS was also characterized by combination of 96-well plate collection of elutes from HPLC analysis and microplate spectrophotometer, in which the scavenging activities of free radical produced by DPPH of each fraction could be directly investigated by the analysis of microplate reader. This study quickly screened the contribution of CSGS fractions to the antioxidant activity and online identified the corresponding active constituents. The results indicated that the combination of LC-MS(n) and 96-well plate assay system established in this paper would be a useful strategy for correlating the chemical profile of TCMs with their bioactivities without isolation and purification. PMID- 20580509 TI - Derivatization of thiols under flow conditions using two commercially available propiolate esters. AB - In the present study we report new data on the reaction of three representative thiols--captopril (CAP), cysteine (CYS) and N-acetylcysteine (NAC)--with two commercially available propiolate esters--methyl-propiolate (MP) and butyl propiolate (BP)--under flow conditions. The reactions were investigated on-line using sequential injection analysis (SI) and the formed derivatives were monitored spectrophotometrically at 285 nm. The effect of critical parameters of the reaction such as the pH, the temperature and the amount concentration of the reagents were studied in detail including stopped-flow (SF) experiments. Both reagents were found to be suitable for the automated derivatization of thiols, although MP offered faster kinetics compared to BP. The applicability of the procedures was demonstrated by the development of SI methods for the dissolution studies of CAP tablets with satisfactory results. PMID- 20580510 TI - Monoliths with chiral surface functionalization for enantioselective capillary electrochromatography. AB - The state-of-the-art in CEC enantiomer separations with monolithic capillary columns is comprehensively reviewed. The various types of monolithic columns comprising in situ organic polymer monoliths, molecularly imprinted polymer (MIP) monoliths, silica monoliths and monoliths made from particles are discussed with a focus on materials' synthesis, chemistry and properties as well as column aspects. Monolithic MIP-type porous layer open-tubular (PLOT) columns are treated herein as well. From this survey of the literature, the authors come to the conclusion that monolithic silica capillaries appear to become the preferred column type for CEC enantiomer separations of low-molecular drugs and other chiral pharmaceuticals or chemicals. PMID- 20580511 TI - Simultaneous quantification of glycine- and taurine-conjugated bile acids, total bile acids, and choline-containing phospholipids in human bile using 1H NMR spectroscopy. AB - Bile acids, phospholipids, and cholesterol are the major lipid components in human bile. The composition of bile is altered in various cholestatic diseases, and determining such alterations will be of great clinical importance in understanding the pathophysiology of these diseases. A robust method for the simultaneous quantification of major biliary lipids--glycine-conjugated bile acids (GCBAs), taurine-conjugated bile acids (TCBAs), total bile acids (TBAs) and choline-containing phospholipids (choline-PLs) has been devised using (1)H NMR spectroscopy. Bile samples were obtained from patients with various hepatopancreatobiliary diseases (n=10) during an endoscopic retrograde cholangiopancreatography (ERCP) examination. Peak areas of metabolite-signals of interest were obtained simultaneously by deconvoluting the experimental spectrum, making the present method robust. GCBAs and TCBAs have been quantified using the peak areas of their characteristic methylene (CH(2)) signals resonating at 3.73 and 3.07 ppm, whereas TBA and choline-PLs were quantified using their methyl (CH(3)) and trimethylammonium (-N(+)(CH(3))(3)) signals resonating at 0.65 and 3.22 ppm respectively. The present method was compared with an NMR-based literature method (which involves dissolving bile in DMSO), and a good correlation was observed between the two methods with regression coefficients - 0.97, 0.99, 0.98 and 0.93 for GCBAs, TCBAs, TBAs, and choline-PLs respectively. This method has the potential to be extended to in vivo applications for the simultaneous quantification of various biliary lipids non-invasively. PMID- 20580512 TI - Analysis of soy isoflavone plasma levels using HPLC with coulometric detection in postmenopausal women. AB - A reliable chromatographic method for the determination of soy isoflavones (genistein, daidzein and glycitein) using a coulometric detection has been developed and applied to analyse plasma of postmenopausal women. The chromatographic separation was performed on a C18 reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. Coulometric detection was carried out at +0.500 V. A careful and rapid solid phase extraction procedure on hydrophilic/lipophilic cartridges was chosen for plasma sample purification with and without hydrolysis obtaining good extraction yield values for all the analytes (>90.0%). The enzymatic hydrolysis step was necessary for the determination of the total amount of soy isoflavones. The limit of quantitation was 0.5 ng mL(-1) for genistein and 0.25 ng mL(-1) for daidzein and glycitein. The method was found to be precise and accurate. Thus, the proposed method is suitable for the analysis of soy isoflavones (free and total amounts) in plasma of postmenopausal women under treatment with the SoymenGN dietary supplement. PMID- 20580513 TI - Ultra high performance liquid chromatography tandem mass spectrometry analysis of quorum-sensing molecules of Candida albicans. AB - Candida albicans is generally one of the most commonly isolated fungal pathogen from human body. It is a frequent cause of nosocomial infections, bloodstream infections, urinary infections and mucosal infections of oral cavity and vagina C. albicans can grow as hyphae, pseudohyphae, or budding yeast. Morphological conversion of a yeast form to pseudohyphal or hyphal one is often characterized by the change of commensal status to an invasive form. Farnesol and tyrosol can participate in these transformation processes as quorum sensing molecules together with some physical-chemical factors. A new analytical method for identification and quantification of biologically active substances farnesol and tyrosol using ultra high performance liquid chromatography (UHPLC) in connection with tandem mass spectrometry was developed. The analytes were separated on Acquity BEH C18 analytical column using binary mobile phase consisting of acetonitrile and formic acid 0.075% (75:25) at flow-rate 0.20 ml/min. SRM (selected reaction monitoring) mode was applied in order to ensure sufficient selectivity and sensitivity using the first most intensive transition as a quantitative (121>77 and 205>121) and second one for the confirmation purposes (121>93 and 205>109). The method was validated in terms of linearity (>0.9994), precision (0.5-3.8% RSD), accuracy (78.9-106.0%), LOD (limit of detection) and LOQ (limit of quantitation). The method can serve as an analytical tool for the detection and determination of quorum-sensing molecules in biological samples. PMID- 20580514 TI - Difficulties with gum elastic bougie intubation in an academic emergency department. AB - BACKGROUND: The difficulties with gum elastic bougie (GEB) use in the emergency department (ED) have never been studied prospectively. OBJECTIVES: To determine the most common difficulties associated with endotracheal intubation using a GEB in the ED. METHODS: We conducted a prospective, observational study of GEB practices in our two affiliated urban EDs with a 3-year residency training program and an annual census of 150,000 patients. Laryngoscopists performing a GEB-assisted intubation completed a structured data form after laryngoscopy, recording patient characteristics, grade of laryngeal view (using the modified Cormack-Lehane classification), reason for GEB use, and problems encountered. Data were analyzed using standard statistical methods and 95% confidence intervals. RESULTS: A GEB was used for 88 patients. The overall success rate was 70/88 (79.6%; 95% confidence interval [CI] 71.1-88.0%). The GEB failure rate of the first laryngoscopist was 25/88 (28.4%; 95% CI 21.0-40.3%), with the two most common reasons being: inability to insert the bougie past the hypopharynx in 13 (52%; 95% CI 32.4-71.6%) and inability to pass the endotracheal tube over the bougie in six (24%; 95% CI 7.3-40.7). CONCLUSIONS: The GEB is a helpful rescue airway device, but emergency care providers should be aware that failure rates are relatively high at a teaching institution. PMID- 20580515 TI - Treating critical illness caused by the 2009 H1N1 influenza A virus. AB - BACKGROUND: The 2009 H1N1 influenza A pandemic has set the world spinning, unexpectedly producing significant morbidity and mortality in young, otherwise healthy patients. DISCUSSION: As the virus spreads across the Northern Hemisphere, emergency physicians are confronted with the challenging task of caring for the many that become critically ill from this pathogen. With the exception of a few observational studies and case reports, there is little information to guide the emergency physician in resuscitating and delivering critical care to a rapidly deteriorating patient. Many moribund patients with 2009 H1N1 influenza A infection require non-conventional critical care therapies. CONCLUSION: In this article, we describe the case of a critically ill patient with confirmed 2009 H1N1 influenza A infection. After a brief review of the unique characteristics of this virus, we discuss the management of critically ill patients burdened by infection with 2009 H1N1 influenza A. PMID- 20580516 TI - Can intraocular pressure measurements be used to screen for elevated intracranial pressure in emergency department patients? AB - BACKGROUND: Handheld measurement of intraocular pressure (IOP) has been previously shown to accurately predict elevated intracranial pressure (ICP) in neurosurgical patients. Handheld tonometry may have clinical utility in the prediction of elevated ICP among a cohort of emergency department (ED) patients receiving lumbar puncture (LP). OBJECTIVE: To ascertain the sensitivity and specificity of IOP for the prediction of elevated ICP in ED patients undergoing LP. METHODS: In this prospective observational pilot study, all ED patients over the age of 18 years and undergoing LP in the ED for any reason were eligible to participate. Study participants had IOP measured with the Tono-Pen XL (Reichert, Inc., Depew, NY) while in the supine position before LP. OP was measured in the lateral recumbent position. Elevated IOP was defined as>=20mm Hg; elevated ICP was defined as>=20mm H(2)O. RESULTS: There were 82 patients screened and 46 patients enrolled at the time of interim analysis. Of the 46 patients, 32 had a successful LP in the lateral recumbent position. There were 18/32 patients with a successful LP in the lateral recumbent position who had elevated opening pressure; 9/32 patients with a successful LP had an elevated IOP. Furthermore, 4/9 patients with elevated IOP also had an elevated opening pressure. There was only one patient who had elevated IOP, elevated ICP, and diagnostic cerebrospinal fluid (sensitivity 24%, 95% confidence interval [CI] 9-48%; specificity 63%, 95% CI 32-88%; positive predictive value 28%, 95% CI 14-47%; negative predictive value 72%, 95% CI 53-96%). CONCLUSIONS: Handheld tonometry has poor sensitivity and specificity for the prediction of increased ICP, and should not be used as a screening tool in the ED. PMID- 20580517 TI - Utilization of emergency medical services by patients with acute coronary syndromes in the Arab Gulf States. AB - BACKGROUND: Emergency Medical Services (EMS) play a central role in caring for patients with acute coronary syndromes (ACS). To date, no data exist on utilization of EMS systems in the Arab Gulf States. OBJECTIVE: To examine EMS use by patients with ACS in the Gulf Registry of Acute Coronary Events (Gulf RACE). METHODS: Gulf RACE was a prospective, multinational study conducted in 2007 of all patients hospitalized with ACS in 65 centers in six Arab countries. Data were analyzed based on mode of presentation (EMS vs. other). RESULTS: Of 7859 patients hospitalized with ACS through the emergency department (ED), only 1336 (17%) used EMS, with wide variation among countries (2% in Yemen to 37% in Oman). Younger age (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.03-1.15 per 10-year decrement), presence of chest pain (OR 1.73; 95% CI 1.48-2.03), prior myocardial infarction (OR 1.58; 95% CI 1.34-1.86), prior percutaneous coronary intervention (OR 1.27; 95% CI 1.02-1.59), family history of premature coronary disease (OR 1.25; 95% CI 1.09-1.51), and current smoking (OR 1.30; 95% CI 1.13-1.50) were independently associated with not utilizing EMS. Patients with ST-segment elevation myocardial infarction/left bundle branch block myocardial infarction who were transported by EMS were significantly less likely to exhibit major delay in presentation, and were significantly more likely to receive favorable processes of care, including shorter door-to-electrocardiogram time, more frequent coronary reperfusion therapy, and thrombolytic therapy within 30 min of arrival at the ED. CONCLUSION: Despite current recommendations, fewer than 1 in 5 patients with ACS use EMS in the Arab Gulf States, highlighting a significant opportunity for improvement. Factors causing this underutilization deserve further investigation. PMID- 20580518 TI - Spontaneous perforation of acalculous gall bladder presenting as acute abdomen. AB - BACKGROUND: Acute abdominal pain is commonly encountered in the emergency department (ED), but a diagnosis of gall bladder perforation (GBP) is rarely considered in the absence of predisposing factors. OBJECTIVES: This article will highlight the risk factors, diagnosis, and management of GBP, a rare but potentially life-threatening biliary pathology. CASE REPORT: A 73-year-old diabetic man presented to the ED with a 12-h history of severe upper abdominal pain. He was hemodynamically stable, but abdominal examination showed distention, guarding, and diffuse tenderness. Abdominal X-ray study showed mildly distended small bowel loops without any air-fluid levels. Abdominal sonography revealed mild ascites and pericholecystic fluid collection but no gall bladder calculi. Laboratory reports documented a white blood cell count of 13,700/mm(3) and elevated serum amylase of 484 IU/L. A contrast-enhanced computed tomography (CT) scan of the abdomen suggested discontinuity of the gall bladder wall along with fluid accumulation in the pericholecystic, perihepatic, right subphrenic, and right paracolic spaces. In view of the possibility of spontaneous GBP developing as a complication of acute acalculous cholecystitis, laparotomy was planned. At surgery, several liters of bile-stained peritoneal fluid were aspirated and inspection of the gall bladder revealed a perforation at the fundus. After cholecystectomy, the patient had an uneventful recovery. CONCLUSION: The diagnosis of spontaneous gall bladder perforation should be considered in elderly patients presenting to the ED with symptoms and signs of peritonitis even in the absence of pre-existing gall bladder disease. Abdominal CT scan is an invaluable tool for the diagnosis, and early surgical intervention is usually life-saving. PMID- 20580519 TI - Achilles tendon rupture must be excluded in the neutral, non-fractured ankle X ray study. AB - BACKGROUND: Rupture of the Achilles tendon (TA) is a common injury. Nevertheless, there is significant potential for missing the diagnosis on initial presentation. We investigated the potential role of lateral ankle X-ray studies in aiding diagnosis. OBJECTIVES: To determine the potential role of radiographs of the ankle in assisting in the diagnosis of Achilles tendon ruptures. METHODS: In a regional trauma unit, 27 patients with confirmed TA rupture at operation had the "tibio-first metatarsal angle" measured as an indication of ankle neutrality. A neutral ankle was defined as an angle of<=100 degrees . Twenty-seven patients with intact TA were used as controls. RESULTS: The mean angle in the TA rupture group was 88 degrees (range 70-120 degrees ) and 125 degrees (104-146 degrees ) in the control group (p<0.001). CONCLUSIONS: In cases of TA rupture, the ankle adopts a more dorsiflexed position than in the ankle with an intact TA. We believe that an ankle joint adopting a neutral position on a lateral X-ray study of the ankle provides a clue to help reduce the rate of missed TA ruptures at initial presentation. PMID- 20580520 TI - Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome. AB - OBJECTIVE: To explore contexts of experiences of physical activity perceived as beneficial or harmful for CFS patients. METHODS: A qualitative study with empirical data from two focus groups with purposive sampling. Mean age was 50, two of ten participants were male, and social demographics varied. Participants were invited to share stories of good as well as bad experiences concerning physical activity. Data were analysed with systematic text condensation. RESULTS: Participants were not averse to physical activity, but specific preconditions would determine how the activity was perceived. Physical activity was experienced as helpful and enjoyable, especially related to leisure activities where flexible and individual adaptation was feasible. Non-customized activity may precipitate set-backs giving patients the impression of losing control and being betrayed by their bodies. Strategies to review energy usage in daily life could adjust expectations, diminish stress load and assist in approaching a more appropriate priority and balance. CONCLUSION: Self-management, body awareness and physical activity of choice combined with facilitation and advice from health care professionals is essential to achieve a positive outcome. PRACTICE IMPLICATIONS: Exercise programmes should be adapted, paced, and self-managed in accordance with personal preferences and activity levels to be beneficial and empowering for CFS patients. PMID- 20580521 TI - Development and pilot testing of an online screening decision aid for men with a family history of prostate cancer. AB - OBJECTIVE: This study aimed to develop and pilot test an online screening decision aid (DA) for men with a family history of prostate cancer. METHODS: Eligible men (with no previous prostate cancer diagnosis) were recruited through relatives attending a urology outpatient clinic. Men evaluated the DA in two stages. First, they appraised a paper-based version using a questionnaire (n=22). Second, the same men were asked to reflect on an interactive web-based version via a semi-structured telephone interview (n=20). RESULTS: Men evaluated both forms of the DA positively. Of the paper-based version, the majority of participants found the DA useful (91%), and that it contained enough information to make a screening decision (73%). All participants reported that the online DA was easy to use and navigate. Most participants reported that a website was their preferred mode of receiving prostate cancer screening information (70%). CONCLUSION: The developed DA may represent the first online decision-making tool designed specifically for men with a family history prostate cancer that presents age and risk specific information to the user. PRACTICE IMPLICATIONS: Comprehensive evaluations of the efficacy and impact of educational interventions such as this are crucial to improve services for individuals making informed screening decisions. PMID- 20580522 TI - Special sections on shared decision making and HIV/AIDS. PMID- 20580523 TI - Progesterone concentration, estradiol pretreatment, and dose of gonadotropin releasing hormone affect gonadotropin-releasing hormone-mediated luteinizing hormone release in beef heifers. AB - We examined whether progesterone (P4)-induced suppression of LH release in cattle can be overcome by an increased dose of exogenous gonadotropin-releasing hormone (GnRH) or pretreatment with estradiol (E2). In Experiment 1, postpubertal Angus cross heifers (N = 32) had their 2 largest ovarian follicles ablated 5 d after ovulation. Concurrently, these heifers were all given a once-used, intravaginal P4-releasing insert (CIDR), and they were randomly assigned to be given either prostaglandin F(2alpha) (Low-P4) or no treatment (High-P4) at follicle ablation, and 12 h later. Six days after emergence of a new follicular wave, half of the heifers in each group (n = 8) were given either 100 or 200 microg of GnRH i.m. Plasma luteinizing hormone (LH) concentrations were higher in the Low- vs High-P4 groups, and in heifers given 200 vs 100 microg of GnRH (mean +/- SEM 15.4 +/- 2.2 vs 9.1 +/- 1.2, and 14.8 +/- 2.1 vs 9.8 +/- 1.4 ng/mL, respectively; P < or = 0.01). Ovulation rate was higher (P = 0.002) in the Low-P4 group (15/16) than in the High-P4 group (6/16), but it was not affected by GnRH dose (P = 0.4). In Experiment 2, heifers (n = 22) were treated similarly, except that 5.5 d after wave emergence, half of the heifers in each group were further allocated to be given either 0.25 mg estradiol benzoate i.m. or no treatment, and 8 h later, all heifers were given 100 microg GnRH i.m. Both groups treated with E2 (Low- and High-P4) and the Low-P4 group without E2 had higher peak plasma LH concentrations compared to the group with high P4 without E2 (12.6 +/- 1.8, 10.4 +/- 1.8, 8.7 +/ 1.3, and 3.9 +/- 1.2 ng/mL, respectively; (P < 0.04)). However, E2 pretreatment did not increase ovulation rates in response to GnRH (P = 0.6). In summary, the hypotheses that higher doses of GnRH will be more efficacious in inducing LH release and that exogenous E2 will increase LH release following treatment with GnRH were supported, but neither significantly increased ovulation rate. PMID- 20580524 TI - Patterns of care in surgery for ovarian cancer in Europe. AB - Quality of surgery is one of the most important determinants of the outcome in ovarian cancer patients. Surgery by a gynaecological oncologist in a specialised, high-volume environment and removal of all visible tumours are associated with a higher likelihood of favourable outcome for patients with advanced-stage ovarian cancer. Population-based studies in Europe however show that a substantial number of patients do not receive optimal surgical care. Less than half of the patients suffering from advanced-stage ovarian cancer are operated by a gynaecological oncologists. Also the proportion of patients operated in a high-volume or specialised hospital is lower than 50%. In a substantial number of patients, minimum standard procedures are not performed and optimal tumor debulking is not achieved. To improve the quality of care, efforts are needed to develop and implement robust evidence-based European guidelines, provide surgical training for gynaecological oncologists and establish comprehensive cancer networks with sufficient resources. PMID- 20580525 TI - Propensity for home death among Taiwanese cancer decedents in 2001-2006, determined by services received at end of life. AB - CONTEXT: The discrepancy between patients' preferred and actual place of death highlights the dilemma inherent in achieving their preferences for home death. Research on determinants of home death has been limited largely by focusing on individual-level factors and somewhat on health care resources at the primary hospital and regional levels. OBJECTIVES: To investigate factors associated with home death, specifically, services received by cancer patients at the end of life (EOL). METHODS: This was a retrospective cohort study using administrative data from 201,201 Taiwanese cancer decedents in the period 2001-2006. RESULTS: Rates of home death decreased significantly over time (from 35.67% to 32.39%). Dying at home was associated with patient demographics (gender, age, and marital status) and disease characteristics (cancer type, metastatic status, postdiagnosis survival time, and comorbidity level). Taiwanese cancer patients were less likely to die at home if they received care from a medical oncologist and in hospitals or regions with abundant health care resources. Furthermore, Taiwanese cancer patients were less likely to die at home if they used life-sustaining treatments (intensive care unit care, cardiopulmonary resuscitation, intubation, and mechanical ventilation) in the last month of life. However, multiple emergency room visits in the last month of life and receiving hospice care increased Taiwanese cancer patients' propensity to die at home. CONCLUSION: Despite the causal ambiguity in interpreting our research findings, they indicate that using life-sustaining treatments at EOL not only exacts a substantial toll from patients, family members, and society, but also decreases the likelihood of dying at home. PMID- 20580526 TI - In-clinic use of electronic pain diaries: barriers of implementation among pain physicians. AB - OBJECTIVES: The aim of this study was to examine barriers to the use of electronic diaries within the clinic setting and determine outcome differences between patients who used electronic diaries to monitor their progress with summary data feedback and patients who monitored their progress with paper diaries without summary data feedback. METHODS: One hundred thirty-four (n=134) chronic pain patients were asked to monitor their pain, mood, activity interference, medication use, and pain location on either a paper or electronic diary immediately before each monthly clinic visit for 10 months. Patients and their treating physicians in the electronic diary group (n=67) were able to observe changes in their ratings whereas patients using the paper diaries (n=67) had no feedback about their data entry. RESULTS: Most participants believed that completing pain diaries was beneficial; yet, only 23% of patients in the experimental condition felt that the data from the electronic diaries improved their care and less than 15% believed that their doctor made a change in their treatment based on the summary diary information. CONCLUSION: In general, treating physicians were positive about the use of electronic diaries, although they admitted that they did not regularly incorporate the summary data in their treatment decision making because either they forgot or they were too busy. Future studies in understanding barriers to physicians' and patients' use of diary data to impact treatment outcome are needed to improve care for persons with chronic pain. PMID- 20580528 TI - Vocal process avulsion. AB - Vocal process avulsion is a rare condition in which laryngeal trauma causes a separation of the vocal process from the body of the arytenoid cartilage. Typically symptoms are dysphonia and shortness of breath during phonation. Strobovideolaryngoscopy, laryngeal electromyography, and laryngeal computed tomography are helpful in establishing this important and sometimes elusive diagnosis. Several treatment modalities have been reported with varying success. We report four new cases, review four cases reported previously by the senior author, and suggest approaches to diagnosis and optimal treatment of vocal process avulsion. PMID- 20580527 TI - Instability of physical anxiety symptoms in daily life of patients with panic disorder and patients with posttraumatic stress disorder. AB - The present study examined severity as well as degree and temporal pattern of instability of DSM-IV-based bodily symptoms of anxiety (BSA) in daily life of 26 panic disorder (PD) patients, 17 posttraumatic stress disorder (PTSD) patients, and 28 healthy controls (HC) during 1 week, using electronic diaries. The ecological momentary assessment around every 3h during wake times was accepted well by patients. Compared to HC, patient groups exhibited elevated instability of BSA. BSA instability was more pronounced in PTSD than PD (p<0.005), even after controlling for mean symptom level. Numbers of symptomatic episodes were comparable in PTSD and PD, but the duration of symptom-free episodes was shorter in PTSD than PD. Results indicate that PTSD patients are particularly burdened by fluctuations in somatic symptoms of anxiety, implying perceived unpredictability and uncontrollability. Electronic diaries can be applied in innovative ways to provide novel insights into the phenomenology of anxiety disorders that may not be captured well by retrospective interviews and questionnaires. PMID- 20580529 TI - Evolution of hemiplegic attacks and epileptic seizures in alternating hemiplegia of childhood. AB - To delineate the evolution of non-epileptic and epileptic paroxysmal events in alternating hemiplegia of childhood (AHC), we reviewed clinical information of nine patients (4-40 years) with AHC. Paroxysmal abnormal ocular movements, head turning, and tonic, clonic, or myoclonic limb movements were the initial symptoms (birth-8m) in each patient. Ictal electroencephalography (EEG) of these episodes, as well as hemiplegic periods that accompanied these symptoms later in infancy showed unremarkable findings or generalized slow background activity. Presumptive epileptic seizures appeared at 2-16y in seven patients: generalized tonic, clonic, myoclonic, tonic-clonic, or complex partial seizures often accompanied by cyanosis or prolonged respiratory arrest. Ictal EEGs recorded in four patients revealed focal slow or fast activities during facial or limb twitching, and widespread sharp waves or polyspike-wave activities during clonic/myoclonic seizures. Four patients with neonatal disease onset showed lower psychomotor developmental achievements compared with other patients, and experienced repeated status epilepticus followed by progressive deterioration. Cerebellar atrophy and hippocampal high signal changes on magnetic resonance imaging were common to this group with severe phenotypes. Apart from the paroxysmal motor symptoms accompanying the hemiplegic episodes, many AHC patients suffer from true epilepsies during childhood. Status epilepticus in AHC is linked to severe outcome with psychomotor deterioration. The variations in clinical phenotypes may imply multiple causative genes for AHC. This variation should be considered while managing patients with this disorder. PMID- 20580530 TI - Neurocognitive performance in children aged 9-12 years who present putative antecedents of schizophrenia. AB - BACKGROUND: We previously developed a novel method of identifying children aged 9 12 years who may be at elevated risk of developing schizophrenia and the spectrum disorders because they present a triad of putative antecedents of schizophrenia (ASz). The present study aimed to determine whether ASz children also present neurocognitive deficits that are commonly observed in patients with schizophrenia. METHODS: Twenty-eight ASz children and 28 typically-developing (TD) children without the antecedents of schizophrenia completed a battery of neurocognitive tests assessing seven domains of function: General intelligence, scholastic achievement, verbal memory, visual memory, working memory, executive function (EF)-verbal fluency, and EF-inhibition. RESULTS: Relative to TD children, the ASz group showed poorer performance on all neurocognitive tests (mean Cohen's d effect size=0.52). In linear regression analyses, group status (ASz vs. TD) significantly predicted scores on the general intelligence, verbal memory, working memory, and EF-inhibition domains (p<0.05). The severity of problems on each of the individual antecedents comprising the antecedent triad did not relate strongly to performance on the neurocognitive domains. CONCLUSIONS: Children aged 9-12 years who present multiple antecedents of schizophrenia display poorer neurocognition than healthy peers on several domains showing pronounced deficits in schizophrenia, first-episode psychosis, and youth with prodromal symptoms. Longitudinal follow-up is necessary to determine the extent to which poorer neurocognitive performance is specific to those who develop schizophrenia. PMID- 20580531 TI - Does dopamine mediate the psychosis-inducing effects of cannabis? A review and integration of findings across disciplines. AB - General population epidemiological studies have consistently found that cannabis use increases the risk of developing psychotic disorders in a dose-dependent manner. While the epidemiological signal between cannabis and psychosis has gained considerable attention, the biological mechanism whereby cannabis increases risk for psychosis remains poorly understood. Animal research suggests that delta-9-tetrahydrocannabinol (THC, the main psychoactive component of cannabis) increases dopamine levels in several regions of the brain, including striatal and prefrontal areas. Since dopamine is hypothesized to represent a crucial common final pathway between brain biology and actual experience of psychosis, a focus on dopamine may initially be productive in the examination of the psychotomimetic effects of cannabis. Therefore, this review examines the evidence concerning the interactions between THC, endocannabinoids and dopamine in the cortical as well as subcortical regions implicated in psychosis, and considers possible mechanisms whereby cannabis-induced dopamine dysregulation may give rise to delusions and hallucinations. It is concluded that further study of the mechanisms underlying the link between cannabis and psychosis may be conducted productively from the perspective of progressive developmental sensitization, resulting from gene-environment interactions. PMID- 20580532 TI - Emergence of clinical strains of Mycoplasma genitalium harbouring alterations in ParC associated with fluoroquinolone resistance. AB - Surveillance for antimicrobial resistance in Mycoplasma genitalium clinical strains is extremely limited as culturing of strains from clinical specimens is still difficult. We therefore conducted a non-cultural assessment of fluoroquinolone resistance of M. genitalium clinical strains by analysing the quinolone-resistance determining regions (QRDRs) of the gyrA and parC genes. The QRDRs amplified from M. genitalium DNA taken from urine specimens of 28 men with non-gonococcal urethritis positive for M. genitalium by polymerase chain reaction were sequenced. An amino acid change (Phe-108-->Iso) in GyrA was found in one specimen, and the same change was accompanied by an amino acid change (Lys-97- >Arg) in ParC in another specimen. A single amino acid change (Ser-83-->Asn, Asp 87-->Tyr or Asp-87-->Val) in ParC was also found in three other respective specimens without alterations in GyrA. No alterations in GyrA and ParC were found in the remaining 23 specimens. The alterations of Ser-83-->Asn, Asp-87-->Tyr and Asp-87-->Val in ParC found in 3 (10.7%) of 28 specimens were analogous to those commonly observed in fluoroquinolone-resistant mutants of other Mycoplasma and Ureaplasma spp. M. genitalium harbouring mutations associated with fluoroquinolone resistance in the parC gene may have emerged clinically and the prevalence may be ca. 10% in Japan. PMID- 20580533 TI - Intravesical gentamicin for recurrent urinary tract infection in patients with intermittent bladder catheterisation. AB - Clean intermittent catheterisation (CIC) of the bladder is used to imitate normal bladder emptying in patients with bladder dysfunction. CIC is associated with urinary tract infection (UTI) that may be difficult to treat in the case of antimicrobial resistance. The aim of this study was to establish the effect and safety of intravesical gentamicin treatment in such settings. In 2009, intravesical gentamicin treatment was started in selected patients. Here we describe our experience with two patients treated until March 2010. Two patients using CIC suffering recurrent UTI with multiresistant Escherichia coli were treated with daily administration of 80 mg intravesical gentamicin. On treatment they appeared asymptomatic. During 8- and 9-month follow-up they were free of UTI, urine cultures were negative and there were no side effects. A systematic review was conducted through searches of PubMed and other databases. Clinical trials that met the eligibility criteria and displayed the efficacy or safety of intravesical aminoglycoside treatment in patients using CIC were studied. Study selection was performed by two independent reviewers. Eight studies were included for review. Owing to study heterogeneity, a meta-analysis could not be performed. Of four controlled studies using neomycin or kanamycin, two demonstrated a significant reduction in bacteriuria, whilst two other trials did not. One case series on neomycin/polymyxin showed that the majority of patients still developed bacteriuria. Three case series using gentamicin all pointed towards a significant reduction in bacteriuria and UTIs. There were no clinically relevant side effects reported but follow-up in all studies was limited. Although data are limited, intravesical treatment with gentamicin might be a reasonable treatment option in selected patients practicing CIC who suffer recurrent UTIs with highly resistant microorganisms. PMID- 20580534 TI - Risk factors and treatment outcomes of community-onset bacteraemia caused by extended-spectrum beta-lactamase-producing Escherichia coli. AB - The purpose of this study was to identify risk factors for extended-spectrum beta lactamase (ESBL)-producing Escherichia coli amongst community-onset bacteraemia and to evaluate treatment outcomes. From the database of a nationwide surveillance programme for bacteraemia, data from patients with community-onset E. coli bacteraemia were analysed. Patients with ESBL-producing E. coli bacteraemia were compared with those with non-ESBL-producing bacteraemia. The overall proportion of ESBL-producers was 9.5% (82/865) amongst community-onset E. coli bacteraemia cases. Healthcare-associated infection, underlying liver disease and primary bacteraemia were significant independent factors associated with ESBL producing E. coli bacteraemia (P<0.05). There was a trend toward mortality being higher in the ESBL group compared with the non-ESBL group (15.0% vs. 7.6%; P=0.096). ESBL production was found to be an independent factor associated with mortality after adjusting for confounding variables (odds ratio=2.99, 95% confidence interval 1.01-8.84; P=0.048), along with severe sepsis, higher Pitt bacteraemia score, primary bacteraemia, pneumonia and underlying liver disease (P<0.05). ESBL-producing E. coli is a significant cause of bacteraemia, even in patients with community-onset infections, predicting higher mortality, particularly in patients with primary bacteraemia, underlying liver disease or healthcare-associated infection. PMID- 20580535 TI - Antiparasitic activity of alkaloids from plant species of Papua New Guinea and Australia. AB - New drugs are needed to help overcome the increasing problem of drug resistance in parasites that cause diseases such as malaria and trypanosomiasis. In this study, alkaloid compounds isolated from extracts of the plants Flindersia amboinensis, Stephania zippeliana and Voacanga papuana from Papua New Guinea and Flindersia acuminata from Australia were examined for their antiparasitic activity against Plasmodium falciparum strains and Trypanosoma brucei brucei as well as their cytotoxicity against the mammalian cell lines HEK 293 and HeLa. The most active compound, dimethylisoborreverine (DMIB), showed submicromolar activity, with 50% inhibitory concentration (IC(50)) values between 20 nM and 810 nM both against drug-sensitive and drug-resistant P. falciparum strains, along with moderate selectivity against T. b. brucei and mammalian cells. Stage specificity studies revealed that P. falciparum trophozoite-stage parasites were more susceptible to DMIB than ring- or schizont-stage parasites. DMIB-treated trophozoites showed changes in food vacuole morphology, with an apparent reduction in haemozoin formation that does not appear to be inhibited via the direct binding of haem. These findings suggest a potential for indole alkaloids from Flindersia spp. as new antiparasitic agents. PMID- 20580537 TI - NMR cogwheel phase cycling determination with web tools: amplitude-modulated z filter MQMAS sequence. AB - Our recent method based on the use of web tools (XML and XSLT) for constructing cogwheel phase cycles is extended to the selection of two symmetrical coherence transfer pathways in the case of an amplitude-modulated z-filter MQMAS sequence. For all spins (I=3/2, 5/2, 7/2 and 9/2) and all MQ experiments we compare cogwheel phase cycling with the traditional "nested" phase cycling. The principal difference in the number of phase cycling steps lies in the use of digitizer phase. For nested phase cycling, this number depends on the use of reference receiver phase or digitizer phase, while cogwheel phase cycling does not. As an illustration we consider the case of a+/-3QMAS experiment for spin I=7/2 system applied to cobalt-59 in [Co(NH3)6]Cl3 powder. We also explore the selection of two non-symmetrical coherence transfer pathways in the case of an amplitude modulated shifted-echo MQMAS sequence. PMID- 20580536 TI - Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae and Escherichia coli isolates possessing blaVIM-1 in Greece. AB - Amongst nalidixic acid-resistant, ciprofloxacin-susceptible Escherichia coli and Klebsiella pneumoniae clinical isolates recovered over a 5-month period from inpatients and outpatients of Attikon University General Hospital (Athens, Greece), only one E. coli was positive for qnrB2 and one K. pneumoniae was positive for qnrA1. Both isolates were extended-spectrum beta-lactamase-negative, metallo-beta-lactamase-positive and carried the bla(VIM-1) gene. Neither of the isolates had mutations in gyrA and parC or carried aac(6')-Ib-cr or qepA. The K. pneumoniae isolate also harboured bla(CMY-13) on the same transferable plasmid with qnrA1. This is the first report of a qnrA1-positive K. pneumoniae and qnrB2 positive E. coli harbouring a concurrent bla(VIM-1) gene. PMID- 20580538 TI - Apatite-forming ability of titanium compound nanotube thin films formed on a titanium metal plate in a simulated body fluid. AB - We compared the apatite-forming ability of a sodium titanate nanotube thin film, an anatase-type titanium dioxide nanotube thin film, and a silver nanoparticle/silver titanate nanotube nanocomposite thin film, in simulated body fluid. The ability of the silver nanoparticle/silver titanate nanotube nanocomposite thin film is slightly higher than that of the anatase-type titanium dioxide nanotube thin film and significantly higher than that of the sodium titanate nanotube thin film. The high ability of the silver nanoparticle/silver titanate nanotube nanocomposite thin film is a newly observed phenomenon, which is probably due to the crystal structure of silver titanate--specifically, to the surface atomic arrangement, the large amount of Ti-OH formed on the nanotube surface, or both. The anatase-type titanium dioxide nanotube thin film and the silver nanoparticle/silver titanate nanotube nanocomposite thin film may have bright prospects for future use in implant materials such as artificial joints. The silver nanoparticle/silver titanate nanotube nanocomposite thin film is particularly promising for its antibacterial properties. PMID- 20580539 TI - Interfacial properties of oleosins and phospholipids from rapeseed for the stability of oil bodies in aqueous medium. AB - Oleosins are plant proteins associated with phospholipids in seed oil bodies. The ability of oleosins to aid in the emulsification and stabilization of oil bodies is well known, but little information is available on their interaction with phospholipids at the interface between oil bodies and aqueous medium. Oil body reconstitution at various phospholipid/oleosin ratios was carried out to observe how rapeseed oleosins of 20kDa and rapeseed phospholipids affect oil body stability. Phospholipids are needed to stabilize oil droplets, but oleosins are mandatory to avoid coalescence. We thus characterized how phospholipids affect the interfacial properties of oleosins at pHs 5.5 and 8.5, by analyzing the adsorption kinetics and interfacial dilational rheology. We observed a synergic effect between oleosins and phospholipids in increasing surface pressure at both pHs. This kind of effect was also observed for the dilational modulus at pH 5.5. A thermodynamic approach highlights these synergic interactions between oleosins and phospholipids through a positive deviation from ideality. PMID- 20580541 TI - Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women. AB - Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. PMID- 20580540 TI - Effects of arsenic exposure during the pre- and postnatal development on the puberty of female offspring. AB - The (As) arsenic exposure is a risk factor for causing disturbances in the endocrine organs. OBJECTIVE: To evaluate if sub-chronic As exposure during the pre- and postnatal development causes disturbances in the puberty. Moreover, determine adverse effects of As on the ovarian follicle and adrenocortical cell maturation. METHODS: Females adult Wistar rats were exposed to sodium arsenite at 3 ppm calculated as As in drinking water from mating, gestation. Following the birth, the female offspring continued exposured to As via lactation. Weaned pups received the same As treatment as mothers, until they were 1-4 months (mo) old. At these ages, blood sampling and tissue harvest were done. The tissues were fixed in situ with 4% paraformaldehyde in phosphate buffer. After the perfusion the ovaries, uterus, adrenal glands were harvested, dissected out, weighted. The ovaries and the adrenal glands were processed to paraffin and sectioned at 5 MUM and stained with hematoxylin and eosin for light microscopy. STATISTICAL ANALYSIS: Comparisons between groups were made by unpaired t-test or nonparametric Mann-Whitney test as appropriate. RESULTS: 100% As treated rats at 1 mo of age were at diestrous stage, with low estradiol E2. As treatment caused disturbances in the morphology of the ovarian cell consisting in DNA damage evidenced by picknotic chromatin, cariorexis, significant cytoplasmic vacuolization and also vasculature damaged. Arrest in follicle maturation was also present. CONCLUSIONS: We found that the onset of puberty in the As treated rats was 1 mo delayed since vagina was still closed, the vaginal smear showed that they were at diestrus stage with plasma low E2 levels. PMID- 20580542 TI - Gender and skeletal muscle characteristics in subjects with chronic obstructive pulmonary disease. AB - BACKGROUND: The influence of gender in the clinical expression of COPD has received important attention. Limited information exists regarding gender differences in the skeletal muscle characteristics in COPD subjects. The present study was aimed to determine the differences in the skeletal muscle characteristics in men and women with and without COPD. METHODS: For comparison we studied 24 female (61 +/- 9 years) and 30 male (65 +/- 8 years) COPD patients with similar disease severity. In addition healthy subjects, 17 women (58 +/- 8 years), and 9 men (57 +/- 8 years) were studied. Pulmonary function, health status, six minute walk distance test (6MWD) and vastus lateralis muscle biopsy were assessed. Fiber type proportion, fiber type cross sectional area (CSA), capillary counts, and activity of citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase (HAD) and lactate-dehydrogenase (LDH) were determined. RESULTS: Pulmonary function, health status and 6MWD were similar in male and female COPD patients. Fiber type distribution was similar between women (I = 42 +/- 9%, IIA = 39 +/- 13%, IIX = 19 +/- 7%) and men (I = 39 +/- 13%, IIA = 38 +/- 9%, IIX = 29 +/- 10%) with COPD, as well as CSA, capillarity and enzymes (CS 8.59 +/- 1.6 vs.9.74 +/- 2.6, HAD 9.03 +/- 1.9 vs. 9.84 +/- 2.5, LDH 124 +/- 48 vs. 151 +/- 68 MUmol min(-1) g(-1)). In normal subjects a decrease in type IIX fibers CSA was found in women compared with men (3703 +/- 1478 vs. 5426 +/- 1386 MUm(2), respectively). CONCLUSIONS: Female and male with COPD have similar skeletal muscle characteristics; it is possible that the disease blurs the gender differences. On the other hand, there seems to be fewer differences in muscle characteristics between older men and women, perhaps due to lower male testosterone levels and physical inactivity. PMID- 20580543 TI - Investigations of biological processes in Austrian MBT plants. AB - Mechanical biological treatment (MBT) of municipal solid waste (MSW) has become an important technology in waste management during the last decade. The paper compiles investigations of mechanical biological processes in Austrian MBT plants. Samples from all plants representing different stages of degradation were included in this study. The range of the relevant parameters characterizing the materials and their behavior, e.g. total organic carbon, total nitrogen, respiration activity and gas generation sum, was determined. The evolution of total carbon and nitrogen containing compounds was compared and related to process operation. The respiration activity decreases in most of the plants by about 90% of the initial values whereas the ammonium release is still ongoing at the end of the biological treatment. If the biogenic waste fraction is not separated, it favors humification in MBT materials that is not observed to such extent in MSW. The amount of organic carbon is about 15% dry matter at the end of the biological treatment. PMID- 20580544 TI - MD recognition by MDR gene regulators. AB - Multidrug resistance (MDR) mechanisms provide responses that sense and extrude arrays of diverse drugs from cellular environments. To do this, MDR functions rely on two linked features--multidrug recognition (MD) and allosteric linkages to drug binding. Crystal structures of drug-bound BmrR and QacR complexes offered the first insights into the details of drug recognition and the canonical view of MD recognition. Recent structural reports provide further support for the canonical theme as well as variations thereof. Multiple drug-bound TtgR and BmrR structures facilitate proposals of binding models, which agree with promiscuous binding and drug-binding profiles. Significantly, the canonical view may be a useful framework to guide future structural interpretations and model proposals. This will be important as alternative depictions of MD recognition become available through more structure determinations. PMID- 20580545 TI - Does socioeconomic status influence the prospect of cure from colon cancer--a population-based study in Sweden 1965-2000. AB - AIM OF STUDY: Differences in the survival of colon cancer patients by socioeconomic status have been demonstrated in several populations, but the underlying reasons for the differences are not well understood. By simultaneously estimating the proportion of patients cured from colon cancer and the survival times of the 'uncured' we hope to increase understanding of how socioeconomic status affects survival following a diagnosis of colon cancer. METHODS: We conducted a population-based cohort study of 58,873 patients diagnosed with colon cancer in Sweden 1965-2000. Socioeconomic status was classified based on occupation. We fitted mixture cure models and Poisson regression models adjusted for age, sex and calendar period. RESULTS: We observed higher excess mortality, lower proportion cured and shorter survival times among the uncured in patients from lower socioeconomic groups compared to the highest socioeconomic group. There was no evidence that the gap between the socioeconomic groups reduced over time. Farmers had the lowest odds of cure (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.75-0.95) compared to higher non-manual workers followed by self employed (0.91, 0.81-1.03), manual workers (0.93, 0.85-1.03) and lower non-manual workers (0.98, 0.89-1.08). CONCLUSION: Patients from lower socioeconomic groups in Sweden experience worse survival following a diagnosis of colon cancer. Differences exist in both the cure proportion and the survival time of the uncured, suggesting that socioeconomic differences cannot be attributed solely to lead time bias.Although this study has furthered our understanding of socioeconomic differences in survival, more detailed studies are required in order to identify, and subsequently remove, the underlying reasons for the differences. PMID- 20580546 TI - Informed decision making does not affect health-related quality of life in lung cancer screening (NELSON trial). AB - BACKGROUND: It is believed that making an informed decision about (screening) participation is associated with better health-related quality of life (HRQoL) outcomes. This is the first study in cancer screening to explore this association in subjects participating in a lung cancer computed tomography (CT) screening trial. METHODS: Participants that made either an informed decision to participate (n = 155) or not (n = 133) were selected for this study. Differences in HRQoL, measured as generic HRQoL (Short Form 12 [SF-12] and EuroQol questionnaire [EQ 5D]), anxiety/distress (State-Trait Anxiety Inventory [STAI-6], Impact of Event Scale [IES] and Consequences of Screening-Lung Cancer [COS-LC]), were tested with Mann-Whitney U tests and ANOVA at three assessment points (when deciding about participation, before trial randomisation and 2 months after receiving the CT result). RESULTS: Subjects who made an informed decision to participate had no better scores than those who did not make an informed decision for 23 out of 24 HRQoL comparisons, except for a better mean score for mental health (Mental Component Summary (MCS) = 53.9 +/- 9.2 versus 51.0 +/- 10.1, p = 0.003) before randomisation. For subjects with an indeterminate CT result (n = 64), no significant differences were found between subjects with (n = 35) or without (n = 29) an informed decision. CONCLUSION: Subjects who did not make an informed decision to participate in lung cancer CT screening trial did not experience worse HRQoL during screening than subjects who did make an informed decision, either in general or after receiving an indeterminate result. PMID- 20580547 TI - The unclear zone in phase II clinical trials. AB - OBJECTIVE: There appears to be considerable confusion about the interpretation of phase II clinical trial conclusions as contrasted with the alternative (HA) and null (H0) hypotheses. This study was conducted to evaluate whether there is congruence with numerical results of phase II trials and their overall verbal conclusions. METHODS: A literature search of 2006 and 2007 phase II clinical trials was conducted. The alternative and null hypotheses were noted as were point estimates with confidence intervals (CIs). These were compared with the final conclusions and concordance and discordance rates were calculated. RESULTS: A total of 152 eligible analyses were reviewed. The point estimates were below H0 in 42 (27.6%) trials, above HA in 60 (39.4%) trials and between H0 and HA (i.e. the grey zone) in 50 (32.9%) trials. Thirty-three (21.7%) trials reported negative conclusions, 111 (73.0%) reported positive conclusions and 8 (5.3%) were ambiguous. All 60 trials in which the point estimate was greater than HA reported positive conclusions, as did 40/50 (80.0%) of trials with point estimates in the grey zone. CONCLUSIONS: There exist inconsistencies and ambiguities in the conclusions drawn from phase II trials, particularly when results are in the grey zone (greater than H0 but less than HA). This may make the integration of phase II trials in phase III trial development strategies difficult and better understanding of the statistical properties of phase II clinical trials is required. PMID- 20580548 TI - The role of biochemical engineering in the production of biofuels from microalgae. AB - Environmental changes that have occurred due to the use of fossil fuels have driven the search for alternative sources that have a lower environmental impact. First-generation biofuels were derived from crops such as sugar cane, corn and soybean, which contribute to water scarcity and deforestation. Second-generation biofuels originated from lignocellulose agriculture and forest residues, however these needed large areas of land that could be used for food production. Based on technology projections, the third generation of biofuels will be derived from microalgae. Microalgae are considered to be an alternative energy source without the drawbacks of the first- and second-generation biofuels. Depending upon the growing conditions, microalgae can produce biocompounds that are easily converted into biofuels. The biofuels from microalgae are an alternative that can keep the development of human activity in harmony with the environment. This study aimed to present the main biofuels that can be derived from microalgae. PMID- 20580549 TI - Two-step SSCF to convert AFEX-treated switchgrass to ethanol using commercial enzymes and Saccharomyces cerevisiae 424A(LNH-ST). AB - It is well known that simultaneous saccharification and co-fermentation (SSCF) reduces cellulosic ethanol production cost compared to separate hydrolysis and fermentation (SHF). However, the traditional SSCF process of converting Ammonia Fiber Expansion (AFEX) pretreated switchgrass to ethanol using both commercial enzymes and Saccharomyces cerevisiae 424A(LNH-ST) gave reduced ethanol yield due to lower xylose consumption. To overcome this problem we have developed a two step SSCF process, in which xylan was hydrolyzed and fermented first followed by the hydrolysis and fermentation of glucan. Important parameters, such as temperature, cellulases loading during xylan hydrolysis and fermentation, initial OD(600) for inoculation of S. cerevisiae 424A(LNH-ST), and pH, were studied for best performance. Compared with traditional SSCF, the two-step SSCF showed higher xylose consumption and higher ethanol yield. The sugar conversion was also enhanced from 70% by enzymatic hydrolysis to 82% by two-step SSCF. One important finding is that the residue from enzymatic hydrolysis plays a significant role in reducing xylose consumption and ethanol metabolic yield during SSCF. PMID- 20580550 TI - Enzymatic grafting of simple phenols on flax and sisal pulp fibres using laccases. AB - Flax and sisal pulps were treated with two laccases (from Pycnoporus cinnabarinus, PcL and Trametes villosa, TvL, respectively), in the presence of different phenolic compounds (syringaldehyde, acetosyringone and p-coumaric acid in the case of flax pulp, and coniferaldehyde, sinapaldehyde, ferulic acid and sinapic acid in the case of sisal pulp). In most cases the enzymatic treatments resulted in increased kappa number of pulps suggesting the incorporation of the phenols into fibres. The covalent binding of these compounds to fibres was evidenced by the analysis of the treated pulps, after acetone extraction, by pyrolysis coupled with gas chromatography/mass spectrometry in the absence and/or in the presence of tetramethylammonium hydroxide (TMAH) as methylating agent. The highest extents of phenol incorporation were observed with the p-hydroxycinnamic acids, p-coumaric and ferulic acids. The present work shows for the first time the use of analytical pyrolysis as an effective approach to study fibre functionalization by laccase-induced grafting of phenols. PMID- 20580551 TI - Synthesis and pharmacological evaluation of 1,1,3-substituted urea derivatives as potent TNF-alpha production inhibitors. AB - A three substituted urea derivative, SA13353 (compound 1a), exhibited potent inhibitory activity against lipopolysaccharide (LPS)-induced TNF-alpha production. We focused on the 1,1-substituted moiety (R(1) and R(2)) of SA13353 and investigated substituent effects of this moiety on LPS-induced TNF-alpha production by oral administration in rats. The synthesis of the urea derivatives was performed rapidly in a one-pot manner using a manual synthesizer. Several compounds containing hydrophobic substituents at this moiety showed more potent inhibitory activities than SA13353. PMID- 20580552 TI - NF-kappaB inducing kinase (NIK) inhibitors: identification of new scaffolds using virtual screening. AB - As a wide variety of pro-inflammatory cytokines are involved in the development of rheumatoid arthritis (RA), there is an urgent need for the discovery of novel therapeutic strategies. Among these, the inhibition of the NF-kappaB inducing kinase (NIK), a key enzyme of the NF-kappaB alternative pathway activation, represents a potential interesting approach. In fact, NIK is involved downstream of many tumor necrosis factor receptors (TNFR) like CD40, RANK or LTbetaR, implicated in the pathogenesis of RA. But, up to now, the number of reported putative NIK inhibitors is extremely limited. In this work, we report a virtual screening (VS) study combining various filters including high-throughput docking using a 3D-homology model and ranking by using different scoring functions. This work led to the identification of two molecular fragments, 4H-isoquinoline-1,3 dione (5) and 2,7-naphthydrine-1,3,6,8-tetrone (6) which inhibit NIK with an IC(50) value of 51 and 90 microM, respectively. This study opens new perspectives in the field of the NF-kappaB alternative pathway inhibition. PMID- 20580553 TI - Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69. AB - Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar activity was found for 4 and 5. The synthesis of the two disaccharide mimics is based on an approach that avoids the glycosylation step using known intermediates arising from lactose. The key stage of the synthesis involves the construction of the DNJ unit through an initial C-5 oxidation of the reducing d-glucopyranosyl unit followed by a stereoselective double-reductive aminocyclization of the 1,5-dicarbonyl disaccharide intermediates. PMID- 20580554 TI - Synthesis and anti-HCV activity of 3',4'-oxetane nucleosides. AB - Hepatitis C virus afflicts approximately 180 million people worldwide and currently there are no direct acting antiviral agents available to treat this disease. Our first generation nucleoside HCV inhibitor, RG7128 has already established proof-of-concept in the clinic and is currently in phase IIb clinical trials. As part of our continuing efforts to discover novel anti-HCV agents, 3',4'-oxetane cytidine and adenosine nucleosides were prepared as inhibitors of HCV RNA replication. These nucleosides were shown not to be inhibitors of HCV as determined in a whole cell subgenomic replicon assay. However, 2'-mono/diflouro analogs, 4, 5, and 6 were readily phosphorylated to their monophosphate metabolites by deoxycytidine kinase and their triphosphate derivatives were shown to be inhibitors of HCV NS5B polymerase in vitro. Lack of anti-HCV activity in the replicon assay may be due to the inability of the monophosphates to be converted to their corresponding diphosphates. PMID- 20580555 TI - Coumarins incorporating hydroxy- and chloro-moieties selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II. AB - A series of coumarins incorporating hydroxy-, chloro- and/or chloromethyl moieties in positions 3-, 4-, 6- and 7- of the heterocyclic ring were investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the house-keeping, offtarget isoforms CA I and II, but showed effective, submicromolar inhibition of the transmembrane, tumor-associated isoforms CA IX and XII. The nature and position of the groups substituting the coumarin ring greatly influenced CA inhibitory properties. 6-Hydroxycoumarin showed K(I)s >100 microM against CA I and II, of 0.198 microM against CA IX and of 0.683 microM against CA XII, being thus a selective, efficient inhibitor for the tumor associated over cytosolic isoforms. These compounds are also excellent leads for designing isoform-selective enzyme inhibitors. PMID- 20580556 TI - Dimeric cyclohexane-1,3-dione oximes inhibit wheat acetyl-CoA carboxylase and show anti-malarial activity. AB - A series of dimeric 1,3-cyclohexanedione oxime ethers were synthesized and found to have significant antiplasmodial activity with IC(50)'s in the range 3-12 microM. The most active dimer was tested in the Plasmodium berghei mouse model of malaria and at a dose of 48 mg/kg gave a 45% reduction in parasitaemia. Several commercial herbicides, all known to be inhibitors of maize acetyl-CoA carboxylase, were also tested for antimalarial activity, but were essentially inactive with the exception of butroxydim which gave an IC(50) of 10 microM. PMID- 20580557 TI - Balance problems during obstacle crossing in children with Developmental Coordination Disorder. AB - The present study investigated the visuomotor and balance limitations during obstacle crossing in typically developing (TD) children and those with Developmental Coordination Disorder (DCD) (7-9 years old; N=12 per group). Spatiotemporal gait parameters as well as range and velocity of the centre of mass (COM) were determined in three conditions: overground walking at a self selected speed, crossing a low obstacle and crossing a high obstacle (5% or 30% of the leg length, respectively). Both groups walked more slowly during obstacle crossing than walking over level ground. In addition, both groups exhibited a significant decrease in the spatial variability of their foot placements as they approached the obstacle, which was then negotiated with a similar strategy. There were no differences in approach distance, length of lead and trail step, or lead and trail foot elevation. Compared to walking over level ground, obstacle crossing led to a longer swing phase of the lead and trail foot and increased maximal medio-lateral COM velocity. In children with DCD, however, medio-lateral COM velocity was higher and accompanied by significantly greater medio-lateral COM amplitude. In conclusion, the results indicate that while TD-children and those with DCD exhibit satisfactory anticipatory control and adequate visual guidance, the latter group have a reduced ability to control the momentum of the COM when crossing obstacles that impose increased balance demands. PMID- 20580558 TI - Evaluating visual bias and effect of proprioceptive feedback in unilateral neglect. AB - We propose modified versions of the line-bisection task for assessing visual bias and effect of proprioceptive feedback in unilateral neglect; that is, the verbal line-bisection (VLB) task and the VLB plus pointing task. The VLB task requires only a verbal response to assess pure visual bias. Conversely, the VLB plus pointing task requires both a verbal response and pointing to assess visual and proprioceptive bias. Ten patients with unilateral neglect were administered these tasks on a computer using presentation software. Eight participants showed obvious rightward deviation in the VLB task, and were thus classified as patients with visual neglect. Four participants showed significantly greater deviation in the VLB plus pointing task than in the VLB task, and were thus classified as patients with proprioceptive bias. Visual bias and effect of proprioceptive feedback in unilateral neglect were successfully assessed by these tasks. PMID- 20580559 TI - Hypoxic selectivity and solubility--investigating the properties of A-ring substituted nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-ones (nitroCBIs) as hypoxia-activated prodrugs for antitumor therapy. AB - Nitro seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-ones (nitroCBIs) are a new class of prodrugs for antitumor therapy that undergo hypoxia-selective metabolism to form potent DNA minor groove alkylating agents. Although hindered by poor aqueous solubility, several examples have shown activity against hypoxic tumor cells in vivo. Here we investigate structural properties that influence hypoxic selectivity in vitro, and show that for high hypoxic selectivity nitroCBIs should combine an electron-withdrawing group of H-bond donor capacity on the A-ring, with a basic substituent on the minor groove-binding side chain. Substitution on the A-ring is compatible with the introduction of functionality that can improve water solubility. PMID- 20580560 TI - Development and evaluation of a 68Ga labeled pamoic acid derivative for in vivo visualization of necrosis using positron emission tomography. AB - In this study, we labeled N,N'-bis(diethylenetriamine pentaacetic acid)-pamoic acid bis-hydrazide (bis-DTPA-PA) with the generator produced PET radionuclide gallium-68 and evaluated 68Ga-bis-DTPA-PA as a potential tracer for in vivo visualization of necrosis by positron emission tomography (PET). Radiolabeling was achieved with a decay-corrected radiochemical yield of 63%. Biodistribution and in vivo stability studies in normal mice showed that 68Ga-bis-DTPA-PA is cleared faster from normal tissue than the previously reported 99mTc(CO)3 complex with bis-DTPA-PA which on the other hand is more stable in vivo. 68Ga-bis-DTPA-PA showed a 3.5-5 times higher binding to necrotic tissue than to viable tissue as shown by in vitro autoradiography while no statistically significant increased hepatic uptake was found in a biodistribution study in a mouse model of hepatic apoptosis. Specificity and avidity for necrosis was further evaluated in rats with a reperfused partial liver infarction and ethanol induced muscular necrosis. Dynamic microPET images showed a fast and prolonged uptake of 68Ga-bis-DTPA-PA in necrotic tissue with in vivo and ex vivo images correlating well with histochemical stainings. With necrotic to viable tissue activity ratios of 8-15 on ex vivo autoradiography, depending on the necrosis model, 68Ga-bis-DTPA-PA showed a faster and higher uptake in necrotic tissue than the 99mTc(CO)3 analog. These results show that 68Ga-bis-DTPA-PA specifically binds to necrotic tissue and is a promising tracer for in vivo visualization of necrosis using PET. PMID- 20580561 TI - Pteridine-sulfonamide conjugates as dual inhibitors of carbonic anhydrases and dihydrofolate reductase with potential antitumor activity. AB - Recent evidences suggest that cancer treatment based on combination of cytostatic and conventional chemostatic therapeutics, which are usually cytotoxic, can provide an improved curative option. On the sequence of our previous work on methotrexate (MTX) derivatives, we have developed and evaluated novel MTX analogues, containing a pteridine moiety conjugated with benzenesulfonamide derivatives, thus endowed with the potential capacity for dual inhibition of dihydrofolate reductase (DHFR) and carbonic anhydrases (CA). These enzymes are often overexpressed in tumors and are involved in two unrelated cellular pathways, important for tumor survival and progression. Their simultaneous inhibition may turn beneficial in terms of enhanced antitumor activity. Herein we report the design and synthesis of several diaminopteridine-benzenesulfonamide and -benzenesulfonate conjugates, differing in the nature and size of the spacer group between the two key moieties. The inhibition studies performed on a set of CAs and DHFR, revealed the activities in the low nanomolar and low micromolar ranges of concentration, respectively. Some inhibitors showed selectivity for the tumor-related CA (isozyme IX). Cell proliferation assays using two tumor cell lines (the non-small cell lung carcinoma, A549, and prostate carcinoma, PC-3) showed activities only in the millimolar range. Nevertheless, this fact points out the need of improving the cell intake properties of these new compounds, since the general inhibitory profiles revealed their potential as anticancer agents. PMID- 20580562 TI - Structure-activity relationship of brominated 3-alkyl-5-methylene-2(5H)-furanones and alkylmaleic anhydrides as inhibitors of Salmonella biofilm formation and quorum sensing regulated bioluminescence in Vibrio harveyi. AB - A library of 25 1'-unsubstituted and 1'-bromo or 1'-acetoxy 3-alkyl-5-methylene 2(5H)-furanones and two 3-alkylmaleic anhydrides was synthesized using existing and new methods. This library was tested for the antagonistic effect against the biofilm formation by Salmonella Typhimurium and the quorum sensing regulated bioluminescence of Vibrio harveyi. The length of the 3-alkyl chain and the bromination pattern of the ring structure were found to have a major effect on the biological activity of the 1'-unsubstituted furanones. Remarkably, the introduction of a bromine atom on the 1' position of the 3-alkyl chain did drastically enhance the activity of the furanones in both biological test systems. The introduction of an acetoxy function in this position did in general not improve the activity. Finally, the potential of the (bromo)alkylmaleic anhydrides as a new and chemically easily accessible class of biofilm and quorum sensing inhibitors was demonstrated. PMID- 20580563 TI - 2-acylamino-4,6-diphenylpyridine derivatives as novel GPR54 antagonists with good brain exposure and in vivo efficacy for plasma LH level in male rats. AB - GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor plays an essential role to modulate sex-hormones including GnRH. Thus, antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis. We recently reported 2-acylamino-4,6 diphenylpyridines as the first small molecule GPR54 antagonists with high potency. However, the representative compound 1 showed low brain exposure, where GPR54 acts as a modulator of gonadotropins by binding with its endogenous ligand, metastin. In order to discover compounds that have not only potent GPR54 antagonistic activity but also good brain permeability, we focused on converting the primary amine on the side chain to a secondary or tertiary amine, and finally we identified 15a containing a piperazine group. This compound exhibited high affinity to human and rat GPR54, apparent antagonistic activity, and high brain exposure. In addition, intravenous administration of 15a to castrated male rat suppressed plasma LH level, which indicates the possibility of a small molecule GPR54 antagonist as a novel drug for sex-hormone dependent diseases. PMID- 20580564 TI - Ultrastructure features of the midgut of the female adult Amblyomma cajennense ticks Fabricius, 1787 (Acari: Ixodidae) in several feeding stages and subjected to three infestations. AB - The digestive tract of Amblyomma cajennense, as well as other species of ticks, is divided into the anterior, medium and posterior intestines and is the organ responsible for digestion of blood ingested during the meal on the host. The anterior and posterior regions are derived from the ectoderm and the medium one from the endoderm. In the present ultrastructural study, we analyzed the midgut of females in a semi- and fully engorged stages, on the rabbit host, which was subjected to three infestations, where were analyzed the changes that the epithelial cells went through. The results showed that during the feeding period the outermost layer the intestine is composed of muscle fibres, as observed in those semi-engorged and engorged ones in the 1st infestation and semi-engorged in the 2nd infestation. The cytoplasm of digestive cells of feeding females, and those of the semi-engorged and fully engorged in the 1st, 2nd and 3rd infestations showed some intact regions (preserved organelles) with others were disorganized. Large lipid droplets and protein granules were observed in the cytoplasm of the cells of the intestine in all phases of feeding process. Cytoplasmic spherocrystals were only observed in the semi-engorged and engorged females in the 1st and 2nd infestations. Intense vacuolation was observed in the digestive cells of the midgut of semi-engorged and engorged A. cajennense females in the 2nd infestation and those engorged in the 3rd infestation. The data showed that the gut of the females of the A. cajennense tick is actually going through big changes during the feeding period, which become more pronounced when reinfesting. These changes are probably due to the host immune response that returns antibodies to the ectoparasite and thus acquires resistance to their secreted products. PMID- 20580565 TI - Porosity measurement of solid pharmaceutical dosage forms by gamma-ray transmission. AB - The aim of the present work is the determination of porosity in tablets by using the gamma-ray transmission technique. Tablet dissolution depends on some inherent characteristics of the manufacturing process, such as compression force, tablet volume, density and porosity, nature of excipients, preparation methods and its physical-chemical properties. Porosity is a measure of empty spaces in a material and can be determined by various techniques. In this paper, we propose the use of a gamma-ray transmission technique to obtain the porosity of experimental formulation of tablets. The results of porosity were compared with those obtained by using conventional methodology (density and mercury intrusion). The experimental setup for gamma-ray transmission consists of a gamma-ray source of (241)Am (photons of 59.6 keV and an activity of 3.7 * 10(9)Bq), an NaI(Tl) scintillation detector, collimators and a standard gamma-ray spectrometry electronics. Our results suggest that the gamma-ray transmission technique is a powerful tool for non-destructive porosity quantification of solid pharmaceutical forms and presents smaller errors than those obtained with conventional methodologies. PMID- 20580566 TI - Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: not just a sporadic coincidence--a multi-centre study. AB - INTRODUCTION: Bisphosphonates (BPs) are powerful drugs that inhibit bone metabolism. Adverse side effects are rare but potentially severe such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). To date, research has primarily focused on the development and progression of BRONJ in cancer patients with bone metastasis, who have received high dosages of BPs intravenously. However, a potential dilemma may arise from a far larger cohort, namely the millions of osteoporosis patients on long-term oral BP therapy. PATIENTS AND METHODS: This current study assessed 470 cases of BRONJ diagnosed between 2004 and 2008 at eleven different European clinical centres and has resulted in the identification of a considerable cohort of osteoporosis patients suffering from BRONJ. Each patient was clinically examined and a detailed medical history was raised. RESULTS: In total, 37/470 cases (7.8%) were associated with oral BP therapy due to osteoporosis. The majority (57%) of affected individuals did not have any risk factors for BRONJ as defined by the American Association of Oral and Maxillofacial Surgery. The average duration of BP intake of patients without risk factors was longer and the respective patients were older compared to patients with risk factors, but no statistical significant difference was found. In 78% of patients the duration of oral BP therapy exceeded 3 years prior to BRONJ diagnosis. DISCUSSION: The results from this study suggest that the relative frequency of osteoporosis patients on oral BPs suffering from BRONJ is higher than previously reported. There is an urgent need to substantiate epidemiological characteristics of BRONJ in large cohorts of individuals. PMID- 20580567 TI - Serum CD44 levels predict survival in patients with low-risk myelodysplastic syndromes. AB - Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders that are preferentially diagnosed in the elderly. Aberrant expression of the adhesion receptor CD44 correlates with poor prognosis in various neoplasms. To evaluate the prognostic impact of CD44 in MDS serum levels of soluble CD44 standard (solCD44s) were measured in 130 MDS patients (median age 68 years) using an enzyme-linked immunosorbent assay (ELISA). solCD44s levels were significantly elevated in MDS patients as compared to those of healthy donors (p<0.001) and were found to correlate with distinct FAB and WHO subtypes. The highest levels of solCD44s were found in patients with CMML, in RAEB and in patients with MDS transformed into secondary acute myeloid leukaemia (AML). In univariate analysis elevated levels of solCD44s (cut-off level>688.5ng/ml) correlated significantly with shorter overall survival in MDS patients (12 versus 39 months; p<0.001). In multivariate analysis solCD44s displayed prognostic significance independent of the International Prognosis Scoring System (IPSS). To test for refined prognostication, IPSS risk groups were split into two separate categories based on the solCD44s levels. Using this approach, MDS patients with a shorter survival were identified both in the IPSS low-risk (p=0.037) and in the IPSS intermediate-1-risk group (p=0.015). The CD44s adjusted IPSS defines a cohort of MDS patients with unfavorable prognosis, which might be helpful in risk stratification and in therapeutic algorithms. PMID- 20580568 TI - IFN-gamma enhances killing of methicillin-resistant Staphylococcus aureus by human monocytes more effectively than GM-CSF in the presence of daptomycin and other antibiotics. AB - Because cytokines have been utilized in treatment of sepsis in neonates, we studied the effects of interferon-gamma (IFN-gamma) and GM-CSF on killing of intracellular methicilin-resistant Staphylococcus aureus (MRSA) by human monocyte derived macrophages (MDM) in the presence of daptomycin (Dap), rifampin (Rif), gentamicin (Gen), and combinations of these drugs. MDM infected with MRSA were treated with Dap (1 x MIC), Gen (0.5 x MIC), or Rif (1 x MIC), singly or in combination, with or without cytokines. MDM were lysed and viable bacteria counted. With antibiotics, MDM activated by IFN-gamma had a more rapid and prolonged bacterial killing effect than MDM activated by GM-CSF. This effect was most obvious with the triple-drug combination. In contrast, GM-CSF reduced intracellular killing under most experimental conditions compared to the effect of antibiotics alone. Dap alone and two- and three-drug combinations demonstrated significant killing effect for the 48 h of the assay. IFN-gamma enhanced rapid intracellular killing of MRSA in the presence of triple-drug treatment or Dap alone. GM-CSF in combination with the antibiotics reduced killing under most conditions studied. Further studies to confirm these observations with IFN-gamma activated MDM and other MRSA strains are needed to support clinical trials for difficult-to-treat MRSA infections. PMID- 20580569 TI - Investigation of the noncovalent interactions between anti-amyloid agents and amyloid beta peptides by ESI-MS. AB - This paper describes an efficient and reproducible screening method for identifying low molecular weight compounds that bind to amyloid beta peptides (Abeta) peptides using electrospray ionization mass spectrometry (ESI-MS). Low molecular weight compounds capable of interacting with soluble Abeta may be able to modulate/inhibit the Abeta aggregation process and serve as potential disease modifying agents for AD. The present approach was used to rank the binding affinity of a library of compounds to Abeta1-40 peptide. The results obtained show that low molecular weight compounds bind similarly to Abeta1-42, Abeta1-40, as well as Abeta1-28 peptides and they underline the critical role of Abeta peptide charge motif in binding at physiological pH. Finally, some elements of structure-activity relationship (SAR) involved in the binding affinity of homotaurine to soluble Abeta peptides are discussed. PMID- 20580570 TI - Carbamino group formation with peptides and proteins studied by mass spectrometry. AB - At high pH and in the presence of dissolved CO(2), the N-terminus and epsilon amino groups of amino acids, peptides, and proteins can form carbamino adducts with CO(2), R-NH(2) + CO(2) <--> R-NHCOO(-) + H(+). We report the first study of carbamino group formation by electrospray ionization (ESI) mass spectrometry (MS). Angiotensin II, bradykinin, substance P, and insulin have been studied. A careful optimization of the instrumental parameters was necessary to allow the transfer of the fragile adducts into vacuum for mass analysis. Particularly, dissociation of the adducts in the ion sampling process and pH changes in ESI must be minimized. With these precautions, levels of carbamino group formation of angiotensin II and bradykinin determined from mass spectra agree with those expected to be in solution, calculated from literature equilibrium constants. Thus, ESI MS can quantitatively measure ratios of carbamino adduct to total peptide concentration in solution. Values of equilibrium constants for carbamino group formation with substance P (pK(c) = 4.77 +/- 0.18) and insulin (pK(c) = 4.99 +/- 0.05) are reported for the first time. PMID- 20580571 TI - Effects of postural and visual stressors on myofascial trigger point development and motor unit rotation during computer work. AB - Musculoskeletal complaint rates are high among those performing low-level static exertions (LLSEs), such as computer users. However, our understanding of the causal mechanisms is lacking. It was hypothesized that myofascial trigger point (MTrP) development might be one causal mechanism to help explain these complaints and that static postural and visual demands may be contributing factors. Therefore, the purpose of this experiment was to examine MTrP development and the behavior of multiple parts of the trapezius muscle under postural and mental stress (represented by visual stress) conditions during computer work. Twelve subjects (six male and six female) were monitored for MTrP development via expert opinion, subject self-report, and cyclic changes in EMG median frequency across fourteen spatial locations. Results showed that MTrPs developed after one hour of continuous typing, despite the stress condition. Interestingly, both the high postural and high visual stress conditions resulted in significantly fewer median frequency cycles (3.76 and 5.35 cycles, respectively), compared to the baseline low stress condition (6.26 cycles). Lastly, the MTrP location as well as locations more medial to the spine showed significantly fewer cycles than other locations. Findings suggest that MTrPs may be one causal pathway for pain during LLSEs and both postural and visual demands may play a role in muscle activation patterns, perhaps attributing to MTrP development and resultant discomfort. PMID- 20580572 TI - Myocardial protection with isoflurane during off-pump coronary artery bypass grafting: a randomized trial. AB - OBJECTIVES: To analyze the hemodynamic effects and myocardial injury using troponin-T and creatine phosphokinase (CPK-MB) with isoflurane and compare it with a control group in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. DESIGN: This prospective, randomized study was performed in patients scheduled for elective OPCAB surgery during February 2007 to February 2009. SETTING: Tertiary care, university teaching hospital. PARTICIPANTS: Forty five patients undergoing elective OPCAB surgery. INTERVENTIONS: Patients were randomly allotted to receive either isoflurane (inspired concentration between 1.0% and 2.5%) or propofol (1.5 to 3.5 mg/kg/h) during OPCAB surgery. The concentration of these agents was titrated such that the BIS value was maintained between 50 and 60. MEASUREMENTS AND MAIN RESULTS: The hemodynamic data were measured and recorded after induction of anesthesia (baseline), during the distal anastomosis of each coronary artery, and 5 and 30 minutes after giving protamine. In addition, blood samples for troponin-T and CPK-MB were obtained after induction (baseline), after 6 hours and 24 hours postoperatively. The cardiac index was significantly higher in the isoflurane group at all stages, except during distal anastomosis of the diagonal branch of the left anterior descending artery (p < 0.05). There was a significant increase in troponin-T levels at 6 and 24 hours after surgery in the propofol group (from 0.037 +/- 0.013 ng/mL to 0.098 +/- 0.045 ng/mL and 0.081 +/- 0.025 ng/mL, respectively, p < 0.05). Significant increases in the troponin-T levels were observed at 6 hours (from 0.033 +/- 0.011 ng/mL to 0.052 +/- 0.025 ng/mL, (p < 0.05) in the isoflurane group, and the levels in the propofol group were significantly higher than the isoflurane group at 6 and 24 hours after surgery (p < 0.05). The CPK-MB levels increased in both groups, but were not statistically different. CONCLUSIONS: Isoflurane provides protection against myocardial damage in a clinically used dosage as documented by lower levels of troponin-T in patients undergoing OPCAB surgery. PMID- 20580573 TI - Incomplete left atrial appendage ligation diagnosed intraoperatively using transesophageal echocardiography following mitral valve repair. PMID- 20580574 TI - Preliminary experience in the use of preoperative echo-guided left stellate ganglion block in patients undergoing cardiac surgery. AB - OBJECTIVE: Pulmonary arterial (PA) vasoconstriction in cardiac surgery can originate from the action of combined humoral, endothelial, and sympathetic tone changes. The consequence of PA vasoconstriction is pulmonary hypertension (PHT) and, when present after cardiopulmonary bypass (CPB), can predispose to right ventricular dysfunction. Right ventricular dysfunction after CPB is a serious complication with high mortality rates. The extent to which sympathetic blockade could reduce PA vasoconstriction and reduce PHT is unknown. Pharmacologic stellate ganglion block (SGB) has been associated with a reduction in PHT, but its role and mechanism in cardiac surgery have not been described. Thus, the goal of the study was to test the hypothesis that echo-guided left SGB, performed before the induction of general anesthesia, could prevent PA pressure increases during CPB weaning. DESIGN: A prospective cohort study in cardiac surgical patients. SETTING: A tertiary care university hospital. PARTICIPANTS: Forty cardiac surgical patients. INTERVENTIONS: A left SGB was performed immediately before the induction of general anesthesia under ultrasound guidance and was compared with matched control patients. Standard hemodynamic and electrocardiographic monitoring was performed, and blood gas samples were drawn at specific predetermined time points for analysis. Rhythm disorders, echocardiographic parameters that included wall motion abnormalities, and biochemical parameters of myocardial ischemia were measured by an observer blinded to the allocated group. MEASUREMENTS AND MAIN RESULTS: Marked improvement in the PaO(2)/F(I)O(2) ratio in the SGB group was observed (mean difference = 77 mmHg, p = 0.0001). There were no differences between the groups in PA pressure over time during the procedure; central venous pressure was higher in the SGB group (p =0.0184). Reductions of right ventricular fractional area change (p = 0.0331) and tricuspid annulus displacement (p = 0.0048) were observed in the SGB group. The CK-MB was 1.5 times higher in the SGB group (p = 0.0211), but no patients developed myocardial infarction. CONCLUSIONS: Left SBG was associated with improved oxygenation that could partially explain its mechanism in acute PHT. Further studies are necessary to evaluate the usefulness of this technique in patients with a high risk of PHT during separation from CPB. PMID- 20580575 TI - Double-envelope continuous-wave Doppler flow profile across a tilting-disc mitral prosthesis: intraoperative significance. PMID- 20580576 TI - General anesthesia increases the risk of bacteremia following dental extractions. AB - OBJECTIVE: The influence of oral health status, the number of teeth extracted, and the anesthetic modality used is currently a matter of debate in the prevalence of bacteremia following dental extractions (BDE). The aim of the present study was to analyze the factors affecting the prevalence, duration, and etiology of BDE. STUDY DESIGN: Blood samples were collected from 210 patients at baseline, 30 seconds, 15 minutes, and 1 hour after performing dental extractions. Samples were processed in the Bactec 9240 and the subculture and further identification of the isolates were performed using conventional microbiological techniques. RESULTS: The prevalence of BDE at 30 seconds, 15 minutes, and 1 hour were 71%, 45%, and 12%, respectively. In the multivariate analysis, the "anesthetic modality" (local anesthesia versus general anesthesia) was the only variable related to BDE. CONCLUSION: General anesthesia represents a risk factor for BDE, increasing its prevalence and duration. PMID- 20580577 TI - Lichen sclerosus et atrophicus-like skin lesions in a patient carrying a novel hydroxymethylbilane synthase mutation. PMID- 20580579 TI - Efficient rotational echo double resonance recoupling of a spin-1/2 and a quadrupolar spin at high spinning rates and weak irradiation fields. AB - A modification of the rotational echo (adiabatic passage) double resonance experiments, which allows recoupling of the dipolar interaction between a spin 1/2 and a half integer quadrupolar spin is proposed. We demonstrate efficient and uniform recoupling at high spinning rates (nu(r)), low radio-frequency (RF) irradiation fields (nu(1)), and high values of the quadrupolar interaction (nu(q)) that correspond to values of alpha=nu(1)(2)/nu(q)nu(r), the adiabaticity parameter, which are down to less than 10% of the traditional adiabaticity limit for a spin-5/2 (alpha=0.55). The low-alpha rotational echo double resonance curve is obtained when the pulse on the quadrupolar nucleus is extended to full two rotor periods and beyond. For protons (spin-1/2) and aluminum (spin-5/2) species in the zeolite SAPO-42, a dephasing curve, which is significantly better than the regular REAPDOR experiment (pulse length of one-third of the rotor period) is obtained for a spinning rate of 13 kHz and RF fields down to 10 and even 6 kHz. Under these conditions, alpha is estimated to be approximately 0.05 based on an average quadrupolar coupling in zeolites. Extensive simulations support our observations suggesting the method to be robust under a large range of experimental values. PMID- 20580578 TI - Diagnosis of canine monocytic ehrlichiosis: development of advanced techniques to combat a global disease. PMID- 20580580 TI - An alternative scheme for the multiplexed acquisition of 1D and 2D NMR spectra. AB - Spin system selective 1D (1)H, 2D DQF-COSY and 2D HSQC NMR spectra were recorded in order to fully assign the (1)H and (13)C 1D NMR spectra of an asymmetrical beta-cyclodextrin derivative. Instead of individually accessing the seven sugar anomeric protons by means of long multiplet selective pulses, only short region selective pulses were used. The simultaneously selected anomeric protons were differentiated by allowing their magnetization to evolve under the sole effect of the chemical shift interaction. In each experiment, the seven recorded spectra were linear combinations of the seven desired ones. The combination coefficients were measured and used to obtain almost perfectly separated sugar unit sub spectra. This multiplexed acquisition scheme resulted in a time gain factor of about 2. PMID- 20580581 TI - Sudden death in medium chain acyl-coenzyme a dehydrogenase deficiency (MCADD) despite newborn screening. AB - INTRODUCTION: Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is the most frequent of the fatty acid oxidation disorders (FAOD), a group caused by defects in the mitochondrial B-oxidation of fatty acids. Fatty acid oxidation is critical in supplying energy during periods when glucose is limited or when energy needs are increased beyond the availability of glucose. In MCADD, this energy shortage can result in acute metabolic episodes or sudden death. The prevention of sudden death from MCADD served as the primary impetus to expand newborn screening. However, we have experienced sudden death in four children with MCADD despite their detection by newborn screening. The purpose of this report is to alert others to the danger of sudden death in MCADD even when it is detected by newborn screening, to identify the clinical symptoms that precede sudden death, and to examine the relationship between the newborn screening result and the risk for sudden death. METHODS: We describe these children and their metabolic findings with emphasis on their newborn screening octanoylcarnitine (C8) level, the primary marker for newborn detection of MCADD. We also performed a literature search of cases of sudden death in MCADD in which the clinical status preceding death is described. RESULTS: The newborn screening C8 levels in our four cases were markedly elevated, ranging from 8.4 to 24.8micromol/L (cut off<0.8micromol/L). Only two of the children were homozygous for the common c.985A>G MCAD mutation; the other two were heterozygous for this mutation. Similarly, among the eight reported cases which included MCAD genotypes, five were homozygous for the c.985A>G mutation, while two were heterozygous and one was homozygous for a splice site mutation. Vomiting 12-24h before sudden death was present in all four of our cases, and the review of reported cases of sudden death in MCADD disclosed vomiting as a frequent symptom. CONCLUSION: We suggest that in MCADD (1) a newborn screening C8 level of 6micromol/L or greater represents particular risk of sudden death; (2) that MCAD genotypes other than homozygosity for the c.985A>G mutation are also associated with sudden death; (3) that vomiting is a frequent symptom preceding sudden death; and (4) social support and medical follow-up of these families are crucial in reducing the occurrence of sudden death. PMID- 20580582 TI - Influence of thymidylate synthase gene polymorphisms on total plasma homocysteine concentrations. AB - BACKGROUND: Thymidylate synthase (TS) is a key enzyme that regulates the production of nucleotide synthesis by catalyzing the conversion of deoxyuridylate to thymidylate. Three functional polymorphisms in the TS gene have been identified including: (i) the thymidylate synthase enhancer region (TSER) tandem repeat polymorphism and (ii) the G to C single nucleotide polymorphism (G/C SNP) both of which occur in the 5'untranslated region (UTR) of the TS gene; and (iii) the 6 base pair deletion at base pair 1494 (TS1494del6) located in the 3'UTR. PURPOSE: The purpose of this research was to investigate the relationship between TS polymorphisms and total plasma homocysteine (tHcy) levels. METHODS: The study population consisted of 396 healthy male and female volunteers from Kingston, Ontario and Halifax, Nova Scotia, Canada between 2006 and 2008. The effect of each TS polymorphism on tHcy concentrations was investigated and further analyses were conducted on categorization of polymorphisms based on 5' or 3'UTR. The combined effect of TS polymorphisms on tHcy concentration was also investigated, in addition to interactions between polymorphisms in TS and MTHFR 677C>T and interactions between TS polymorphisms and serum folate and vitamin B(12) status. RESULTS: An association between TS 5'polymorphisms and tHcy concentration was observed (p=0.05). The combined effect of the TS polymorphisms was also found to be associated with tHcy concentration (p=0.05). Additionally, an antagonistic interaction was observed between TS 5'polymorphism and MTHFR 677C>T on tHcy concentrations (p=0.04). CONCLUSIONS: The findings of this research provide evidence of an association between TS polymorphisms and tHcy concentrations. PMID- 20580583 TI - Reduction in imiglucerase dosage causes immediate rise of chitotriosidase activity in patients with Gaucher disease. PMID- 20580584 TI - Multiple endocrine diseases in cats: 15 cases (1997-2008). AB - The objective of this retrospective study was to characterize a population of cats from a tertiary care center diagnosed with multiple endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Medical records of 15 cats diagnosed with more than one endocrine disorder were reviewed. The majority of cats were domestic shorthairs, and the mean age at the time of diagnosis of the first disorder was 10.3 years. The most common combination of disorders was diabetes mellitus and hyperthyroidism. Two cats had concurrent diabetes mellitus and hyperadrenocorticism, one cat had concurrent central diabetes insipidus and diabetes mellitus. A mean of 25.7 months elapsed between diagnoses of the first and second endocrine disorder, but this was variable. This study suggests the occurrence of multiple endocrine disorders is uncommon in cats. PMID- 20580585 TI - [Effectiveness of palifermin in the prevention of oral mucositis in patients with haematological cancers]. AB - OBJECTIVE: To assess the effectiveness of palifermin for the prevention of oral mucositis in patients with haematological cancers. METHODS: Retrospective observational study of cohorts of patients with haematological cancer undergoing cytotoxic therapy causing hematopoietic ablation. The main variable assessed was the duration of the oral mucositis. Secondary variables assessed were incidence of mucositis, febrile or septic neutropenia and the administration of opioids and parenteral nutrition. RESULTS: We included 36 patients in this study, 11 in the group that received palifermin and 25 in the control group. The duration of oral mucositis was 4.6+/-3.1 days (median: 5 days) in the patients treated with palifermin in comparison with 7.4+/-4.0 days (median: 6 days) in patients treated with conventional prophylactic therapy (p<0.05). However, no significant differences were seen in the incidence of mucositis, febrile or septic neutropenia, opioid administration of the use of parenteral nutrition. CONCLUSIONS: Prophylactic treatment with palifermin reduces the duration of oral mucosities in patients with haematological cancer. Further studies are necessary with larger samples to be able to assess palifermin and its influence on other variables, such as incidence of mucositis, sepsis, febrile neutropenia, etc. PMID- 20580586 TI - [Jealousy between siblings in early childhood. Nursing assessment based on a case study]. AB - Childhood jealousy, when a little brother or sister is born, has always been a subject treated within the family environment. Parent's attitude in their interaction with their offspring may increase the response of the jealous child. The emotional expressions of the jealous child may lead to behaviour changes, that may occasionally put the physical integrity of the newborn at risk, since it is the most vulnerable in the family group. In view of the above mentioned, a case of a three-year-old child living with his parents and his nine-month-old sister, is presented. The child shows characteristic behaviour changes of jealousy, such as, rebelliousness, aggressiveness and hyperactivity. The brother's psychomotor discomfort leads to a proneness to accidents for the baby girl and the obvious parental concern. For these reasons nursing intervention in the family group was proposed, based on the theoretical Virginia Henderson Needs Model. The actions will come from the older brother and parents. The aim of the nursing intervention is to lead the behaviour changes in order to re-establish a safe and healthy family environment. PMID- 20580587 TI - Foreign travel, casual sex, and sexually transmitted infections: systematic review and meta-analysis. AB - OBJECTIVES: With increasing international travel it is important to understand how frequent casual travel sex and unprotected intercourse are, and what impact this may have on the risk of acquiring sexually transmitted infections (STIs). METHODS: We conducted a systematic review, and where appropriate meta-analyses, to ascertain the influence of foreign travel on behavior, including new partnerships, unprotected intercourse, and STI acquisition. RESULTS: The pooled prevalence of travel-associated casual sex was 20.4% (95% confidence interval (CI) 14.8-26.7%), with 49.4% (95% CI 38.4-60.5%) of these having unprotected intercourse. The predominant characteristics of people who had new sexual partners abroad were: young age, male gender, single status, and traveling alone or with friends, with a previous history of multiple sexual partners or an STI. People who travel or stay abroad for longer periods and men who have sex with men are at higher risk of developing new sexual partnerships and having unprotected intercourse. The risk of developing an STI is increased up to 3-fold in people who experience casual travel sex. CONCLUSIONS: New sexual partnerships and unprotected intercourse abroad are relatively common. People who develop new sexual partnerships and have unprotected intercourse abroad have an increase risk of STIs. There is, however, a paucity of information related to strategies to prevent the risk of STI acquisition during foreign travel. PMID- 20580588 TI - Human cowpox virus infection acquired from a circus elephant in Germany. AB - A 40-year-old Asian circus elephant developed mouth and trunk ulcers. Three weeks later, her 19-year-old animal warden noticed a vesicle on his forearm, evolving into a scab. Identical cowpox strains were isolated from lesions of the elephant and the warden. Cowpox virus could no longer be isolated after the scab disappeared, but PCR still revealed orthopox DNA. Healing was complete seven weeks later, leaving a 1 cm scar. PMID- 20580590 TI - [Normal tissue tolerance to external beam radiation therapy: peripheral nerves]. AB - Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy...) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. PMID- 20580591 TI - The relationship between body mass index and hip osteoarthritis: a systematic review and meta-analysis. AB - OBJECTIVE: Body mass index, a measure of relative weight, is increasingly recognized as an important risk factor for osteoarthritis, especially in weight bearing joints. The objective was to assess the association between body mass index and hip osteoarthritis susceptibility and investigate the difference between sex, study type and osteoarthritis definition. METHODS: We did electronic searches of Medline, Embase and Cochrane library from the commencement to December 2009. A meta-analysis and meta-regression was executed to quantitatively assess the strength of associations between body mass index and hip osteoarthritis risk. Study-specific incremental estimates were standardized to determine the risk associated with a 5 kg/m(2) increase in body mass index. RESULTS: Fourteen epidemiological studies were included. Our study showed that body mass index was significantly positive associated with hip osteoarthritis risk. A 5-unit increase in body mass index was related to an increased risk of hip osteoarthritis (RR: 1.11; 95%CI: 1.07, 1.16). The magnitudes of associations were similar in women as compared with men (women, RR: 1.10; 95%CI: 1.05, 1.15; men, RR: 1.08; 95%CI: 1.04, 1.12; p > 0.05). The summary estimates were 1.12 (95%CI: 1.02, 1.24) in case-control studies and 1.11 (95%CI: 1.06, 1.16) in cohort studies (p > 0.05). Body mass index was positively associated with hip osteoarthritis defined by radiography and/or clinical symptom (RR: 1.04; 95%CI: 1.00, 1.07) and clinical surgery (RR: 1.16; 95%CI: 1.11, 1.22) with no significant difference (p > 0.05). CONCLUSION: Increased body mass index contributes to a positive effect on susceptibility to hip osteoarthritis. Associations between body mass index and hip osteoarthritis risk do not vary by sex, study design or osteoarthritis definition. PMID- 20580592 TI - [Anti-Mullerian hormone, an endocrine predictor of the response to ovarian stimulation in the bovine species]. AB - The strong between-animal variability in the number of ovulations and embryos produced after ovarian stimulation by gonadotropins is a major limit to the development of embryo biotechnologies in cattle. In reproductive medicine, anti mullerian hormone (AMH) is now widely used as an endocrine marker of the ovarian follicular reserve. In the cow, as in the woman, AMH is secreted by the granulosa cells of growing follicles. We have shown recently that in the cow, AMH is a very good endocrine marker of the population of small antral follicles that constitute the direct target of ovarian stimulatory treatments. AMH concentration measured in plasma before treatment varies between animals and is positively correlated to the number of ovulations and transferable embryos produced after an ovarian stimulatory treatment. Interestingly, AMH concentrations can remain stable over several months for each animal. Moreover, the number of embryos produced after ovarian stimulation is highly repeatable and has a relatively good heritability. From these observations, we propose the determination of AMH concentration in the plasma of a potential donor cow as a simple predictive method to evaluate both its level of ovarian activity and its capacity to produce high or low numbers of embryos. Optimal conditions for implementing this diagnostic test in cattle remain to be defined considering the age, the breed, the physiological status and the environmental factors related to breeding conditions for each animal. PMID- 20580593 TI - [How to start a bibliographic research?]. PMID- 20580594 TI - Sonochemical synthesis and characterization of nano-belt lead(II) coordination polymer: new precursor to produce pure phase nano-sized lead(II) oxide. AB - Nanobelts of new a lead(II) coordination polymer, [Pb(3-pyc)(2)](n) (1), 3-Hpyc=3 pyridinecarboxilic acid were synthesized by a sonochemical method. The new nano structure was characterized by scanning electron microscopy, X-ray powder diffraction, elemental analyses and IR spectroscopy. The thermal stability of compound was studied by thermal gravimetric and differential thermal analyses. After calcination of nano-sized compound 1 at 400 degrees C, pure phase nano sized lead(II) oxide has been produced. PMID- 20580595 TI - Subgrouping patients with low back pain in primary care: are we getting any better at it? AB - Low back pain is a common, disabling condition with high personal and economic costs. Despite clinical guidelines, there have not been tangible reductions in the population prevalence of back pain or its serious long-term consequences. One reason for this might be that the 'one-size fits all approach' advocated by many guidelines fails to target treatments at patients who might benefit the most, thus diluting their potential benefits. Identifying subgroups of patients for whom different treatments are superior has been referred to as the 'Holy Grail' of low back pain research. Maximising the potential for targeted interventions is predicated on better understanding of the prognostic factors that are causally related to clinical outcome and identifying which are a) most predictive of outcome and b) most likely to be modifiable. Systematic identification of key obstacles to recovery in primary care back pain patients from high quality epidemiological studies can inform the development of early, targeted interventions. Only then can closer matching of treatments to patient characteristics be a clinical reality. This paper critically reviews progress in subgrouping for targeted treatment for patients with low back pain, identifies the key arguments for and against subgrouping and highlights the attributes of robust approaches in this field. PMID- 20580596 TI - Plastidial retrograde signalling--a true "plastid factor" or just metabolite signatures? AB - The genetic compartments of plant cells, nuclei, plastids and mitochondria exchange information by anterograde (nucleus-to-organelle) and retrograde (organelle-to-nucleus) signalling. These avenues of communication coordinate activities during the organelles' development and function. Despite extensive research retrograde signalling remains poorly understood. The proposed cytosolic signalling pathways and the putative organellar signalling molecules remain elusive, and a clear functional distinction from the signalling cascades of other cellular perception systems (i.e. photoreceptors or phytohormones) is difficult to obtain. Notwithstanding the stagnant progress, some basic assumptions about the process have remained virtually unchanged for many years, potentially obstructing the view on alternative routes for retrograde communication. Here, I critically assess the current models of retrograde signalling and discuss novel ideas and potential connections. PMID- 20580597 TI - GRAM: A framework for geodesic registration on anatomical manifolds. AB - Medical image registration is a challenging problem, especially when there is large anatomical variation in the anatomies. Geodesic registration methods have been proposed to solve the large deformation registration problem. However, analytically defined geodesic paths may not coincide with biologically plausible paths of registration, since the manifold of diffeomorphisms is immensely broader than the manifold spanned by diffeomorphisms between real anatomies. In this paper, we propose a novel framework for large deformation registration using the learned manifold of anatomical variation in the data. In this framework, a large deformation between two images is decomposed into a series of small deformations along the shortest path on an empirical manifold that represents anatomical variation. Using a manifold learning technique, the major variation of the data can be visualized by a low-dimensional embedding, and the optimal group template is chosen as the geodesic mean on the manifold. We demonstrate the advantages of the proposed framework over direct registration with both simulated and real databases of brain images. PMID- 20580598 TI - Arabinosylated glycopeptide hormones: new insights into CLAVATA3 structure. AB - Secreted peptides are now recognized as important members of hormones that coordinate and specify cellular functions in plants. Recent accumulating evidence shows that secreted peptide hormones are often post-translationally modified, and such modification is critical for their function. In this review, we highlight hydroxyproline arabinosylation, which has been found in several peptide hormones including CLAVATA3 (CLV3), a key peptide controlling stem cell renewal and differentiation in Arabidopsis shoot apical meristem. Arabinosylation of CLV3 is important for its biological activity and for high-affinity binding to its receptor, CLV1. We discuss the physiological functions of known glycopeptide hormones, the structural information on sugar chains, and possible mechanisms of glycosylation. PMID- 20580601 TI - Comparison of artifact correction methods for infant EEG applied to extraction of event-related potential signals. AB - OBJECTIVE: EEG recording is useful for neurological and cognitive assessment, but acquiring reliable data in infants and special populations has the challenges of limited recording time, high-amplitude background activity, and movement-related artifacts. This study objectively evaluated our previously proposed ERP analysis techniques. METHODS: We compared three artifact removal techniques: Conventional Trial Rejection (CTR), Independent Channel Rejection (ICR; He et al., 2007), and Artifact Blocking (AB; Mourad et al., 2007). We embedded a synthesized auditory ERP signal into real EEG activity recorded from 4-month-old infants. We then compared the ability of the three techniques to extract that signal from the noise. RESULTS: Examination of correlation coefficients, variance in the gain across sensors, and residual power revealed that ICR and AB were significantly more successful than CTR at accurately extracting the signal. Overall performance of ICR and AB was comparable, although the AB algorithm introduced less spatial distortion than ICR. CONCLUSIONS: ICR and AB are improvements over CTR in cases where the signal-to-noise ratio is low. SIGNIFICANCE: Both ICR and AB are improvements over standard techniques. AB can be applied to both continuous and epoched EEG. PMID- 20580600 TI - Validation of the Cepheid Xpert Flu A real time RT-PCR detection panel for emergency use authorization. AB - BACKGROUND: In April 2009, the United States Secretary of the Department of Health and Human Services declared a public health emergency concerning the 2009 influenza H1N1 outbreak. This declaration allowed the FDA to issue Emergency Use Authorization (EUA) of approved in vitro diagnostics to detect the 2009 influenza H1N1 in clinical specimens. OBJECTIVES: This report outlines the validation testing of the Cepheid Xpert Flu A Panel for the qualitative detection of 2009 H1N1 viral RNA. STUDY DESIGN: This study was a multi-site, dual-method clinical evaluation comparing the results of testing between the Xpert Panel assay to the FDA-cleared Luminex Molecular Diagnostics xTAG Respiratory Viral Panel (Luminex RVP) assay and the EUA-granted Focus Diagnostics Influenza A/H1N1 (2009) Real Time RT-PCR (Focus H1N1) assay. RESULTS: When compared to Luminex RVP (n=300) for influenza A detection, the Xpert Panel had a sensitivity of 91.2% (95% CI: 85.1 95.4), specificity of 99.4% (95% CI: 96.7-100), positive predictive value (PPV) of 99.2% (95% CI: 95.6-100), and a negative predictive value (NPV) of 93.1% (95% CI: 88.3-96.4). When compared to the Focus H1N1 (n=258) for detection of H1N1, the Xpert Panel had a sensitivity of 92.1% (95% CI: 82.4-97.4), specificity of 100% (95% CI: 98.5-100), PPV of 100% (95% CI: 95.0-100), and a NPV of 97.5% (95% CI: 94.3-99.2). CONCLUSIONS: The results show the Cepheid Xpert Flu A Panel to be comparable to both the Luminex RVP and the Focus H1N1 assays. The Cepheid Xpert Panel was granted an EUA on 24 Dec 2009. PMID- 20580599 TI - Composition and sensory function of the trypanosome flagellar membrane. AB - A cilium is an extension of the cell that contains an axonemal complex of microtubules and associated proteins bounded by a membrane which is contiguous with the cell body membrane. Cilia may be nonmotile or motile, the latter having additional specific roles in cell or fluid movement. The term flagellum refers to the motile cilium of free-living single cells (e.g. bacteria, archaea, spermatozoa, and protozoa). In eukaryotes, both nonmotile and motile cilia possess sensory functions. The ciliary interior (cilioplasm) is separated from the cytoplasm by a selective barrier that prevents passive diffusion of molecules between the two domains. The sensory functions of cilia reside largely in the membrane and signals generated in the cilium are transduced into a variety of cellular responses. In this review we discuss the structure and biogenesis of the cilium, with special attention to the trypanosome flagellar membrane, its lipid and protein composition and its proposed roles in sensing and signaling. PMID- 20580602 TI - Increased anterior brain activation to correct responses on high-conflict Stroop task in obsessive-compulsive disorder. AB - OBJECTIVE: An abnormally increased activation in anterior brain networks, accompanied by normal task performance, has been reported in studies on biological mechanisms of obsessive-compulsive disorder (OCD). We test a hypothesis, that this phenomenon, deemed specific to OCD, will be compromised by a very difficult task, which may lead to reduced cortical information processing and erroneous performance, as found in other disorders such as schizophrenia. METHODS: We designed a new variant of high-conflict Stroop-word-color interference task (Stroop-WCIT) with each incongruent (INC) trial preceded by multiple congruent trials. Event-related potentials (ERPs) were acquired from subjects with OCD and case-matched healthy controls (C). We analyzed ERPs elicited by correct responses to conflict-related INC trials. RESULTS: Our hypothesis found no support. Although the anterior ERPs N200, a negative component within 140-300 ms latency window, was significantly abnormally increased in OCD subjects, their performance accuracy remained normal. CONCLUSIONS: Current findings suggest an enhanced adaptive top-down control in OCD mediated by the prefrontal lateral and dorsal anterior cingulate networks. SIGNIFICANCE: Further studies are warranted to test the hypothesis that increased activity within the anterior network for top-down inhibitory control in OCD may be a part of an adaptive compensatory neural mechanism. PMID- 20580603 TI - Electrophysiological assessment of a case of limb myorhythmia. PMID- 20580604 TI - Effects of a probiotic fermented milk beverage containing Lactobacillus casei strain Shirota on defecation frequency, intestinal microbiota, and the intestinal environment of healthy individuals with soft stools. AB - The effects of drinking a fermented milk beverage that contains Lactobacillus casei strain Shirota (LcS) at 40 billion bacterial cells/bottle for 4 weeks (probiotics, 1 bottle/day) on defecation frequency, intestinal microbiota and the intestinal environment of healthy individuals with soft stools were evaluated. Thirty-four healthy adults who had soft stools were randomised into 2 groups, and the effects of a regular 4-week intake of probiotics were evaluated by a placebo controlled, double-blind, parallel-group comparative design. Defecation frequency significantly decreased after the 4-week intake period compared with before the probiotic treatment. The stool quality significantly improved (hardened) compared to the placebo. Also, the water content of the stools was lower in the probiotic group than in the placebo group. Live LcS was recovered at 6.9 +/- 1.3 and 7.2 +/ 0.8 log(10) CFU per 1g of stool after 2 and 4 weeks, respectively, of probiotic treatment. The number of bifidobacteria in the stools also increased significantly compared with the level before starting the probiotics. The organic acid levels (total, acetic acid, propionic acid, and butyric acid) significantly increased compared with the level before intake in both the probiotic and placebo groups, but they returned to the original levels after the end of the intake period. These results suggest that probiotic fermented milk beverage has an intestine-conditioning effect by improving the frequency of defecation and stool quality and increasing the intrinsic bifidobacteria in healthy individuals with soft stool. PMID- 20580605 TI - End-of-life needs as perceived by terminally ill older adult patients, family and staff. AB - PURPOSE OF THE STUDY: A comparison of inpatient end-of-life needs as perceived by terminally ill older adult patients, family, physicians and nurses, is lacking. This study aimed to compare the importance attributed to different end-of-life needs by terminally ill older adult patients in long-term care facilities, their families and care providers (physicians and nurses). METHOD: This descriptive, cross-sectional study recruited a convenience sample of 451 subjects, including 73 terminally ill older adult patients, 58 family members, 71 physicians and 249 nurses, from two Israeli geriatric centers. RESULTS: This study found a high congruence between the staff and terminally ill older adults and their families regarding most needs identified as important to dying people. The five needs identified as most important by all subjects were: not suffering pain, having no difficulty breathing, maintaining dignity, having someone who listens, and receiving adequate nursing care. The results of this survey suggest that for terminally ill older adult patients and their families, physical care is crucial. In contrast, nurses attribute higher significance to spiritual needs, but this finding may be affected by the fact that the rate of religiosity among nurses was much higher than among all other research groups. CONCLUSIONS: Identifying terminally ill older adults' end-of-life needs may enable nurses and physicians to modify and improve end-of-life care. This could result in a substantial decrease in suffering amongst nursing home terminally ill older adult patients and their families. PMID- 20580606 TI - Treatment non-adherence in teenage and young adult patients with cancer. AB - Adhering to treatment can be a significant issue for many patients diagnosed with chronic health conditions and this has been reported to be greater during the adolescent years. However, little is known about treatment adherence in teenage and young adult (TYA) patients with cancer. To increase awareness of the adherence challenges faced by these patients, we have reviewed the published work. The available evidence suggests that a substantial proportion of TYA patients with cancer do have difficulties, with reports that up to 63% of patients do not adhere to their treatment regimens. However, with inconsistent findings across studies, the true extent of non-adherence for these young patients is still unclear. Furthermore, it is apparent that there are many components of the cancer treatment regimen that have yet to be assessed in relation to patient adherence. Factors that have been shown to affect treatment adherence in TYA patients include patient emotional functioning (depression and self-esteem), patient health beliefs (perceived illness severity and vulnerability), and family environment (parental support and parent-child concordance). Strategies that foster greater patient adherence are also identified. These strategies are multifactorial, targeting not only the patient, but the health professional, family, and treatment regimen. This review highlights the lack of interventional studies addressing treatment adherence in TYA patients with cancer, with only one such intervention being identified: a video game intervention focusing on behavioural issues related to cancer treatment and care. Methodological issues in measuring adherence are addressed and suggestions for improving the design of future adherence studies highlighted, of which there is a great need. PMID- 20580608 TI - New perspectives in tracing vector-borne interaction networks. AB - Disentangling trophic interaction networks in vector-borne systems has important implications in epidemiological and evolutionary studies. Molecular methods based on bloodmeal typing in vectors have been increasingly used to identify hosts. Although most molecular approaches benefit from good specificity and sensitivity, their temporal resolution is limited by the often rapid digestion of blood, and mixed bloodmeals still remain a challenge for bloodmeal identification in multi host vector systems. Stable isotope analyses represent a novel complementary tool that can overcome some of these problems. The utility of these methods using examples from different vector-borne systems are discussed and the extents to which they are complementary and versatile are highlighted. There are excellent opportunities for progress in the study of vector-borne transmission networks resulting from the integration of both molecular and stable isotope approaches. PMID- 20580609 TI - Soil-transmitted helminthiases: implications of climate change and human behavior. AB - Soil-transmitted helminthiases (STHs) collectively cause the highest global burden of parasitic disease after malaria and are most prevalent in the poorest communities, especially in sub-Saharan Africa. Climate change is predicted to alter the physical environment through cumulative impacts of warming and extreme fluctuations in temperature and precipitation, with cascading effects on human health and wellbeing, food security and socioeconomic infrastructure. Understanding how the spectrum of climate change effects will influence STHs is therefore of critical importance to the control of the global burden of human parasitic disease. Realistic progress in the global control of STH in a changing climate requires a multidisciplinary approach that includes the sciences (e.g. thermal thresholds for parasite development and resilience) and social sciences (e.g. behavior and implementation of education and sanitation programs). PMID- 20580607 TI - Placenta as a source of hematopoietic stem cells. AB - The placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic cells in the mouse and human placenta and probe the biological rationale behind its hematopoietic function. As a rest tissue that contains potent hematopoietic stem cells (HSCs), the human placenta could represent (in addition to umbilical cord blood cells) an accessible supplemental source of cells for therapeutic strategies. PMID- 20580610 TI - Cathepsin B proteases of flukes: the key to facilitating parasite control? AB - Cysteine proteases are important virulence factors for parasites. This review will focus on the cathepsin B proteases of trematodes (also known as flukes) which are abundant in juvenile and immature flukes. Recent research, primarily in Fasciola, using inhibitors, RNA interference (RNAi) and vaccination studies indicates that cathepsin Bs play a key role in the biology of trematodes. As these proteases are largely expressed by infective parasite stages, their inactivation by chemotherapy or vaccination will greatly reduce the damage wrought by flukes as they invade host tissues. This validates cathepsin Bs as key strategic targets for fluke control. PMID- 20580611 TI - Immunogenetics of Toxoplasma gondii informs vaccine design. AB - A series of studies over 20 years mapped resistance to toxoplasmic encephalitis in mice to major histocompatibility complex class I (MHC I) and ultimately, more precisely the Ld region. This is consistent with contemporary functional studies that demonstrated a protective role for CD8(+) T cells. Recent studies have demonstrated that the Ld gene product presents a number of immunodominant Toxoplasma gondii-derived peptides in the murine models, providing a paradigm for vaccine design. The almost complete sequencing of the genomes of the predominant strains of T. gondii in conjunction with the development of predictive binding algorithms for MHC I peptides in humans now offers a new opportunity for vaccine development against this medically important pathogen. PMID- 20580612 TI - Clinical considerations for antibiotic choices in the treatment of severe malaria. PMID- 20580613 TI - Specific bacterial genotypes of Mycobacterium tuberculosis cause extensive dissemination and brain infection in an experimental model. AB - Meningeal tuberculosis is a severe type of extrapulmonary disease, which is thought to begin with respiratory infection, followed by hematogenous dissemination and brain infection. Host genetic susceptibility factors and specific mycobacterial substrains could be involved in its development. From an epidemiological study in Colombia, we selected three Mycobacterium tuberculosis clinical strains isolated from the cerebrospinal fluid (CSF) of patients with meningeal tuberculosis, and used them to infect BALB/c mice through the intratracheal route. These strains showed a distinctive spoligotype pattern. The course of infection in terms of strain virulence (mice survival, bacillary loads in lungs), bacilli dissemination and extrapulmonary infection (bacilli loads in blood, brain, liver, kidney and spleen), and immune responses (cytokine expression determined by real time PCR in brain and lung) was studied and compared with that induced by the laboratory strain H37Rv and other five clinical strains isolated from patients with pulmonary TB. All the clinical isolates from meningeal TB patients disseminated extensively through the hematogenous route infecting the brain, producing inflammation in the cerebral parenchyma and meninges, whereas H37Rv and clinical isolates from pulmonary TB patients showed very limited efficiency to infect the brain. Thus, it seems that mycobacterial strains with a distinctive genotype are able to disseminate extensively after the respiratory infection and infect the brain. PMID- 20580614 TI - Is autoimmune limbic encephalitis a channelopathy? PMID- 20580615 TI - Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. AB - BACKGROUND: Voltage-gated potassium channels are thought to be the target of antibodies associated with limbic encephalitis. However, antibody testing using cells expressing voltage-gated potassium channels is negative; hence, we aimed to identify the real autoantigen associated with limbic encephalitis. METHODS: We analysed sera and CSF of 57 patients with limbic encephalitis and antibodies attributed to voltage-gated potassium channels and 148 control individuals who had other disorders with or without antibodies against voltage-gated potassium channels. Immunohistochemistry, immunoprecipitation, and mass spectrometry were used to characterise the antigen. An assay with HEK293 cells transfected with leucine-rich, glioma-inactivated 1 (LGI1) and disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) or ADAM23 was used as a serological test. The identity of the autoantigen was confirmed by immunoabsorption studies and immunostaining of Lgi1-null mice. FINDINGS: Immunoprecipitation and mass spectrometry analyses showed that antibodies from patients with limbic encephalitis previously attributed to voltage-gated potassium channels recognise LGI1, a neuronal secreted protein that interacts with presynaptic ADAM23 and postsynaptic ADAM22. Immunostaining of HEK293 cells transfected with LGI1 showed that sera or CSF from patients, but not those from control individuals, recognised LGI1. Co-transfection of LGI1 with its receptors, ADAM22 or ADAM23, changed the pattern of reactivity and improved detection. LGI1 was confirmed as the autoantigen by specific abrogation of reactivity of sera and CSF from patients after immunoabsorption with LGI1-expressing cells and by comparative immunostaining of wild-type and Lgi1-null mice, which showed selective lack of reactivity in brains of Lgi1-null mice. One patient with limbic encephalitis and antibodies against LGI1 also had antibodies against CASPR2, an autoantigen we identified in some patients with encephalitis and seizures, Morvan's syndrome, and neuromyotonia. INTERPRETATION: LGI1 is the autoantigen associated with limbic encephalitis previously attributed to voltage-gated potassium channels. The term limbic encephalitis associated with antibodies against voltage-gated potassium channels should be changed to limbic encephalitis associated with LGI1 antibodies, and this disorder should be classed as an autoimmune synaptic encephalopathy. FUNDING: National Institutes of Health, National Cancer Institute, and Euroimmun. PMID- 20580616 TI - Natural killer receptors distribution in multiple sclerosis: Relation to clinical course and interferon-beta therapy. AB - NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56(bright) NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-beta-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-beta therapy, may support the analysis of NKR distribution as new biomarkers. PMID- 20580618 TI - GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response. AB - We have previously shown that two injections of 20 MUg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD alum group, higher pre-treatment GADA were associated to more pronounced C peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response. PMID- 20580617 TI - Familial C4B deficiency and immune complex glomerulonephritis. AB - Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schonlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID- 20580619 TI - Economic burden associated with the use of generic antiepileptic drugs in the United States. AB - This study quantifies the economic burden associated with generic-versus-branded use of antiepileptic drugs (AEDs) in the United States. Adult patients with epilepsy receiving carbamazepine, gabapentin, phenytoin, primidone, or zonisamide were selected from the PharMetrics database. By use of an open-cohort design, patients were classified into mutually exclusive periods of generic-versus branded AED use. Annualized cost differences (CDs) between periods were estimated using multivariate regressions. Results were stratified into stable versus unstable epilepsy and newer-generation versus older-generation AEDs. A total of 33,625 patients (52% male, mean age=51 years) were observed. Periods of generic AED treatment were associated with higher medical service costs (adjusted CD [95% CI]=$3186 [$2359; $4012]), stable pharmacy costs ($69 [$-34; $171]), and greater total costs ($3254 [$2403; $4105]) versus brand use. Epilepsy-related costs represented 30% of incremental costs. Similar findings were observed for patients with stable and unstable epilepsy and users of newer-generation and older generation AEDs. Significantly higher health care costs were observed during generic AED use across seizure control and AED subgroups. PMID- 20580620 TI - A case of frontal lobe epilepsy in which amplitude-integrated EEG combined with conventional EEG was useful for evaluating clusters of seizures. AB - Accurate evaluation of status epilepticus or clusters of seizures in patients with epilepsy is a critical issue in epilepsy care units. Although the need for continuous electroencephalographic monitoring has been recognized, it has been difficult to evaluate the frequency of ictal changes in electroencephalography (EEG) data in real time. Amplitude-integrated EEG (aEEG) has been reported to be useful for neuromonitoring, particularly in newborn infants. However, few reports of the utility of aEEG in older children with epilepsy have been published. We employed aEEG in combination with conventional EEG in an 11-year old boy presenting with clusters of seizures and were able to accurately evaluate the frequency of seizures in real time. The combination of aEEG and conventional EEG may be a useful tool in both neonatal intensive care units and epilepsy care units. PMID- 20580621 TI - Ictal extension (dorsiflexion) of the toes in a patient with temporal lobe epilepsy: a new ictal lateralizing sign. AB - Neurologists have analyzed the clinical behaviors that occur during seizures for many years. Several ictal behaviors have been defined in temporal lobe epilepsy (TLE). Ictal behaviors are especially important in the evaluation of candidates for epilepsy surgery. We propose a new ictal lateralizing sign originating from the nondominant hemisphere: extension (dorsiflexion) of the toes (Babinski's, Chaddock's, and Moniz' signs). Our patient is a 16-year-old woman. Her epileptogenic foci were localized to the right neocortical temporal region after noninvasive presurgical investigations. Cranial MRI revealed a right insular lesion compatible with focal cortical dysplasia or cortical tumor. We observed progressive movement of the left leg and, when the patient touched the lateral aspect of the foot to the bed, dorsiflexion of the great toe (Babinski's sign). In other seizures, the patient started a progressive movement of the left leg, rubbing the external border of the left foot on the bed and provoking dorsiflexion of the great toe (Chaddock's sign). The Brissaud reflex component was also observed when the movement was accompanied by internal rotation of the leg and recruitment of the tensor fascia lata, making dorsiflexion more likely to be a reflex response and not voluntary. We also observed forceful passive plantar flexion at the ankle in association with dorsiflexion of the great toe (Moniz' sign). All of these signs were contralateral to ictal seizure onset and to the cerebral epileptogenic lesion. These signs may occur as a result of ictal activation of a specific brain region in this hemisphere. PMID- 20580622 TI - Changes in blood pressure induced by electrical stimulation of the femur in anesthetized rats. AB - The effects of electrical stimulation of the femur, on blood pressure, were examined in anesthetized rats. Two small holes, 3-4 mm apart, were manually drilled into the femur down to the bone marrow. Following this, two stainless steel electrodes were inserted into the holes, and an electrical square wave current was passed between the electrodes. In central nervous system-intact rats, electrical stimulation of the femur at 5 and 10 mA at 20 Hz for 20 s produced an intensity-dependent decrease in mean arterial blood pressure. This response was abolished by severance of the femoral and sciatic nerves ipsilateral to the stimulation. Furthermore, the renal sympathetic efferent nerve activities (as a representative index of vasoconstrictor activities) decreased following the electrical stimulation of the femur. However, in acutely-spinalized rats (spinalized at the cervical level) the same stimulation increased renal sympathetic efferent nerve activities and mean arterial blood pressure. It was concluded that high-intensity electrical stimulation of the femur reflexively affected blood pressure. It can be inferred that the osteal high-threshold receptors and/or fibers are involved in the afferent nerve pathway, and the efferent nerve pathway is the sympathetic vasoconstrictor nerve. The excitatory response properties at the propriospinal level are modified into an inhibitory response by supraspinal structures. PMID- 20580624 TI - [Treatment resistant chronic monoarticular synovitis: Lipoma arborescens]. PMID- 20580623 TI - Pancreatic cancer stem cells - update and future perspectives. AB - Solid tumours are the most common cancers and represent a major therapeutic challenge. The cancer stem cell hypothesis is an attractive model to explain the functional heterogeneity commonly observed in solid tumours. It proposes a hierarchical organization of tumours, in which a subpopulation of stem cell-like cells sustains tumour growth, metastasis, and resistance to therapy. We will present the most recent advances in the cancer stem cell field, with particular emphasis on pancreatic cancer as one of the deadliest human tumours, and highlight open questions and caveats to be addressed in future studies. There is increasing evidence that solid tumours including pancreatic cancer are hierarchically organized and sustained by a distinct subpopulation of cancer stem cells. However, direct evidence for the validity of the cancer stem cell hypothesis in human pancreatic cancer remains controversial due to the limitations of xenograft models but supportive data are now emerging from mouse models using related or different sets of markers for the identification of murine cancer stem cells. Therefore, while the clinical relevance of cancer stem cells remains a fundamental issue for this rapidly emerging field, current findings clearly suggest that specific elimination of these cells is possible and therapeutically relevant. Targeting of signalling pathways that are of particular importance for the maintenance and the elimination of cancer stem cell as the proposed root of the tumour may lead to the development of novel treatment regimens for pancreatic cancer. Here we will review the current literature on pancreatic cancer stem cells and the future perspective of this rapidly emerging field. PMID- 20580625 TI - Near-infrared spectroscopy: a methodology-focused review. AB - Near infrared spectroscopy (NIRS) is a light-based technology used to monitor tissue oxygen status. Refinements to the method since it was first described have extended its applicability to different research and clinical settings due to its non-invasiveness, instrument portability and ease of use. Classic NIRS recordings, based in the Beer-Lambert law, can be used for the trend monitoring of changes in tissue perfusion-oxygenation parting from an arbitrary zero point. However, in order to derive intermittently quantitative values in absolute terms, certain manoeuvres must be performed. More recently, the evolution of the technique has led to the development of instruments that provide an absolute value of regional hemoglobin saturation in a continuous manner. This review will focus on the physical principles of tissue spectroscopy including a brief description of the different operating principles that are currently in use or under development. The theoretical details, experimental procedures and data analysis involved in the measurements of physiological variables using NIRS will be described. The future beyond the scope of NIRS and potential lines of research will also be discussed. PMID- 20580626 TI - Patient selection and prognostication with hypothermia treatment. AB - For infants with perinatal hypoxia-ischaemia, the ability to give an accurate prognosis at different ages enables the clinician to make decisions on the continuation of management, and also assists in discussions regarding further treatment and prognosis with parents and families. This review suggests which outcome markers are still valid, which need new 'cut-off values' and which can no longer be used in cooled infants. The main focus is on convenient bedside technologies such as the amplitude-integrated electroencephalogram that can be easily applied in routine clinical practice. PMID- 20580628 TI - Idiopathic spinal accessory nerve palsy. A case report. AB - Spinal accessory nerve palsy may lead to dysfunction or paralysis of the trapezius muscle. Common causes are iatrogenic or secondary due to trauma, infection or tumour. Idiopathic palsy is considered extremely rare. We present the case of a 42-year-old Caucasian male suffering from a unilateral, isolated paralysis of his ipsilateral trapezius muscle. There was no related trauma, nor any past history of surgical procedures. An electromyographic study confirmed the idiopathic paralysis of the distal segment of the spinal accessory nerve. PMID- 20580627 TI - Plasma adiponectin levels are related to obesity, inflammation, blood lipids and insulin in type 2 diabetic and non-diabetic Trinidadians. AB - AIMS: To determine the relationship between plasma adiponectin levels and obesity, inflammation, blood lipids and insulin resistance in type 2 diabetics (T2DM) and non-diabetics in a patient population in Trinidad. METHODS: A cohort study of a total of 126 type 2 diabetic (42 males and 84 females) and 140 (43 males and 97 females) non-diabetic public clinic attendees were assessed between December 2008 and July 2009. Along with clinical history and anthropometry, adiponectin, TNF-alpha, IL-6, CRP, lipid profile, glucose, and insulin were measured in fasting blood samples and insulin resistance (HOMA-IR) was calculated. RESULTS: Diabetics had higher (p<0.05) glucose, insulin, HOMA-IR, triglycerides (TG), VLDL and systolic blood pressure than non-diabetics, but lower (p<0.05) HDL and adiponectin levels. Adiponectin levels were lower (p<0.05) in obese than in non-obese individuals regardless of diabetic status. There were significant gender differences in HDL, LDL and TG. Among non-obese persons, adiponectin correlated negatively with triglycerides (r=-0.280; adiponectin), IL 6 (r=-0.216; p<0.005), HOMA-IR (r=-0.373; p=000) and positively correlated with HDL (r=0.355; p=0.000). Diabetic status (p=0.025), TNF-alpha (p=0.048) and BMI (p=0.027) were identified as useful predictors of adiponectin by multiple linear regression methods. In addition binary logistic regression analysis found glucose (p=0.001) and adiponectin (p=0.047) to be useful indicators of type 2 diabetes. CONCLUSIONS: Adiponectin decreases with increasing adiposity and insulin resistance. Adiponectin and TNF-alpha appear to be related to differences in the insulin mediated glucose turnover. PMID- 20580629 TI - Acral myxoinflammatory fibroblastic sarcoma. AB - Acral myxoinflammatory fibroblastic sarcoma is a rare low-grade malignant soft tissue tumor, usually observed in the extremities of middle-aged patients. We report a case involving the third finger of the left hand of a middle-aged man. The tumor showed a nodular architecture, with cellular areas, occasional foci of hyalinized fibrosis, and hypocellular areas with a myxoid background. Various neoplastic cells were identified including spindled or rounded epithelioid cells and occasional bizarre giant cells, morphologically mimicking ganglion cells. Tumor cells were strongly immunoreactive for vimentin and variably positive for CD68 and CD34. The tumor was completely removed, without further treatment. PMID- 20580630 TI - Fifth metacarpal neck fracture fixation: Locking plate versus K-wire? AB - INTRODUCTION: Neck fractures of the fifth metacarpal bone can leave sequelae. Surgery is indicated when the displacement of the head in flexion exceeds 45 degrees and/or rotation is impaired. Among available techniques, non-locking mini-plates have the most drawbacks; recently developed locking plates may, however, challenge the preference for K-wires. HYPOTHESIS: The present study compared results between locking plates and intramedullary K-wires. MATERIAL AND METHODS: The series comprised 38 fifth metacarpal fractures: 18 were managed by locking plate (group I) and 20 by intramedullary K-wire (group II). Results were analyzed on subjective and objective criteria (pain, DASH, strength, mobility, time off work, radiology). RESULTS: No significant differences were found for pain, DASH, strength, time off work or head displacement at last follow-up. Active mobility, however, was significantly greater in the K-wire group, with mean relative metacarpophalangeal flexion 59% of healthy-side values in group I vs. 98% in group II, and mean relative extension 89% in group I vs. 99% in group II. Group I showed six complications (three cases of stiffness, one of head necrosis, two of delayed consolidation) vs. seven in group II (three cases of wire migration, three of neurologic lesion, one of esthetic blemish). DISCUSSION: Locking plates with immediate mobilization paradoxically provided poorer mobility at end of follow-up than intramedullary K-wire with 6 weeks' immobilization. The extra cost of locking plates was thus not justified by results. Intramedullary K wire nailing remains the reference technique for the management of displaced fracture of the fifth metacarpal neck. LEVEL OF EVIDENCE: Level IV continuous prospective comparative study. PMID- 20580631 TI - Knowledge, perception and practices of colorectal cancer screening in an ethnically diverse population. AB - BACKGROUND: Colorectal cancer (CRC) screening improves survival and its success depends on the participation of the at-risk population. Few studies have adequately assessed screening knowledge, perception and participation according to birthplace. This study assesses the knowledge and perception of CRC in an ethnically diverse population, and evaluates the association with screening participation and intention. Identification of specific predictors of screening may aid the development of interventions to improve overall CRC screening. METHODS: An interview-based survey, conducted on subjects aged 30-70 years, assessed knowledge and perception towards CRC and screening tests. Primary endpoints were screening participation and intent. Statistical methods used were Chi-square, Mann-Whitney U and logistic regression. RESULTS: A total of 543 subjects (43% males, 53% Australian-born (AB), 63% aged 50 years and above) were recruited. Compared with AB, non-Australian-born (NAB) respondents had poorer knowledge, and NAB background predicted for poorer knowledge independent of sex, education, media and familiarity with CRC patient. Compared with AB respondents aged 50 years and above, NAB respondents had lower screening participation (17.4% vs. 31.8%; P=0.01), lesser intention (75.8% vs. 90.5%; P<0.001), and had received fewer doctors' screening recommendations (16.5% vs. 27.1%; P=0.04). In multivariate analysis, doctors' recommendation, media and improved perception independently predicted screening participation; knowledge and media exposure predicted intent. CONCLUSIONS: The knowledge of CRC and screening is significantly poorer in the immigrant population. Knowledge predicts for greater screening intent. Therefore, implementing language- and culture-specific educational programs involving medical practitioners and media are necessary to improve CRC screening participation rates. PMID- 20580632 TI - Development of a novel TaqMan real-time PCR assay for detecting rubella virus RNA. AB - Although the number of cases of rubella and congenital rubella syndrome has decreased recently in Japan, both are still important health problems. To control rubella infection, a rapid and reliable method for diagnosis of rubella is required as soon as possible. Direct detection of the viral genome in clinical samples is viewed as crucial for laboratory diagnosis. In this study, a novel diagnostic method for rubella virus, based on a fluorogenic real-time PCR (TaqMan) assay, was developed, and its sensitivity for various virus strains was compared with that of a conventional RT-PCR. The new assay allowed more rapid and sensitive detection of the virus than did the conventional RT-PCR, and could detect at least 10 pfu of the native strains in Japan (1a, 1D, 1j). PMID- 20580633 TI - Mitochondrial matrix delivery using MITO-Porter, a liposome-based carrier that specifies fusion with mitochondrial membranes. AB - Mitochondria are the principal producers of energy in cells of higher organisms. It was recently reported that mutations and defects in mitochondrial DNA (mtDNA) are associated with various mitochondrial diseases including a variety of neurodegenerative and neuromuscular diseases. Therefore, an effective mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve this, therapeutic agents need to be delivered into the innermost mitochondrial space (mitochondrial matrix), which contains the mtDNA pool. We previously reported on the development of MITO-Porter, a liposome-based carrier that introduces macromolecular cargos into mitochondria via membrane fusion. In this study, we provide a demonstration of mitochondrial matrix delivery and the visualization of mitochondrial genes (mtDNA) in living cells using the MITO-Porter. We first prepared MITO-Porter containing encapsulated propidium iodide (PI), a fluorescent dye used to stain nucleic acids to detect mtDNA. We then confirmed the emission of red-fluorescence from PI by conjugation with mtDNA, when the carriers were incubated in the presence of isolated rat liver mitochondria. Finally, intracellular observation by confocal laser scanning microscopy clearly verified that the MITO-Porter delivered PI to the mitochondrial matrix. PMID- 20580634 TI - Stimulation of lateral hypothalamic AMPA receptors may induce feeding in rats. AB - Glutamate or its ionotropic receptor (iGluR) agonists, N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxale propionate (AMPA), and kainate (KA) elicit feeding when microinjected into the lateral hypothalamus (LH) of satiated rats. In the present study we investigated the contributions of AMPA and KA receptors (AMPARs and KARs) to feeding initiation. Intense feeding was elicited by LH injection of RS-AMPA (1 and 10 nmol) but not by the isolated, inactive R-AMPA enantiomer (1 and 10 nmol). Further, LH pretreatment with either the non-selective AMPAR/KAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 nmol) or the selective AMPAR antagonist, GYKI 52466 (10 nmol), suppressed AMPA-elicited food intake and, when combined, blocked AMPA-elicited food intake. These findings suggest that LH AMPARs mediate AMPA injection elicited feeding with a possible contribution by KARs. In contrast, CNQX or GYKI 52466 injected into the LH at the onset of the nocturnal period or into fasted rats did not suppress the feeding produced by either condition. RS-AMPA injected into the LH of fasted or nocturnal feeding subjects elicited eating in both conditions; however, the magnitude of the increase was greater in fasted rats. These data suggest that selective stimulation of AMPAR in the LH is sufficient to elicit feeding. In contrast, the results did not provide evidence that AMPAR stimulation is necessary for deprivation-induced or nocturnal eating; however, they did suggest that modulatory interactions may exist between these receptors and these forms of naturally occurring eating behavior. PMID- 20580635 TI - Semantic and acoustic analysis of speech by functional networks with distinct time scales. AB - Speech perception requires the successful interpretation of both phonetic and syllabic information in the auditory signal. It has been suggested by Poeppel (2003) that phonetic processing requires an optimal time scale of 25 ms while the time scale of syllabic processing is much slower (150-250 ms). To better understand the operation of brain networks at these characteristic time scales during speech perception, we studied the spatial and dynamic properties of EEG responses to five different stimuli: (1) amplitude modulated (AM) speech, (2) AM speech with added broadband noise, (3) AM reversed speech, (4) AM broadband noise, and (5) AM pure tone. Amplitude modulation at gamma band frequencies (40 Hz) elicited steady-state auditory evoked responses (SSAERs) bilaterally over primary auditory cortices. Reduced SSAERs were observed over the left auditory cortex only for stimuli containing speech. In addition, we found over the left hemisphere, anterior to primary auditory cortex, a network whose instantaneous frequencies in the theta to alpha band (4-16 Hz) are correlated with the amplitude envelope of the speech signal. This correlation was not observed for reversed speech. The presence of speech in the sound input activates a 4-16 Hz envelope tracking network and suppresses the 40-Hz gamma band network which generates the steady-state responses over the left auditory cortex. We believe these findings to be consistent with the idea that processing of the speech signals involves preferentially processing at syllabic time scales rather than phonetic time scales. PMID- 20580636 TI - GABA acts as a ligand chaperone in the early secretory pathway to promote cell surface expression of GABAA receptors. AB - GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in brain. The fast inhibitory effect of GABA is mediated through the GABA(A) receptor, a postsynaptic ligand-gated chloride channel. We propose that GABA can act as a ligand chaperone in the early secretory pathway to facilitate GABA(A) receptor cell surface expression. Forty-two hours of GABA treatment increased the surface expression of recombinant receptors expressed in HEK 293 cells, an effect accompanied by an increase in GABA-gated chloride currents. In time-course experiments, a 1h GABA exposure, followed by a 5h incubation in GABA-free medium, was sufficient to increase receptor surface expression. A shorter GABA exposure could be used in HEK 293 cells stably transfected with the GABA transporter GAT 1. In rGAT-1HEK 293 cells, the GABA effect was blocked by the GAT-1 inhibitor NO 711, indicating that GABA was acting intracellularly. The effect of GABA was prevented by brefeldin A (BFA), an inhibitor of early secretory pathway trafficking. Coexpression of GABA(A) receptors with the GABA synthetic enzyme glutamic acid decarboxylase 67 (GAD67) also resulted in an increase in receptor surface levels. GABA treatment failed to promote the surface expression of GABA binding site mutant receptors, which themselves were poorly expressed at the surface. Consistent with an intracellular action of GABA, we show that GABA does not act by stabilizing surface receptors. Furthermore, GABA treatment rescued the surface expression of a receptor construct that was retained within the secretory pathway. Lastly, the lipophilic competitive antagonist (+)bicuculline promoted receptor surface expression, including the rescue of a secretory pathway-retained receptor. Our results indicate that a neurotransmitter can act as a ligand chaperone in the early secretory pathway to regulate the surface expression of its receptor. This effect appears to rely on binding site occupancy, rather than agonist-induced structural changes, since chaperoning is observed with both an agonist and a competitive antagonist. PMID- 20580637 TI - Estradiol attenuates multiple tetrodotoxin-sensitive sodium currents in isolated gonadotropin-releasing hormone neurons. AB - Secretion from gonadotropin-releasing hormone (GnRH) neurons is necessary for the production of gametes and hormones from the gonads. Subsequently, GnRH release is regulated by steroid feedback. However, the mechanisms by which steroids, specifically estradiol, modulate GnRH secretion are poorly understood. We have previously shown that estradiol administered to the female mouse decreases inward currents in fluorescently labeled GnRH neurons. The purpose of this study was to examine the contribution of sodium currents in the negative feedback action of estradiol. Electrophysiology was performed on GnRH neurons dissociated from young, middle-aged, or old female mice. All mice were ovariectomized; half were estradiol replaced. The amplitude of the sodium current underlying the action potential was significantly decreased in GnRH neurons from young estradiol treated animals. In addition, in vivo estradiol significantly decreased the transient sodium current amplitude, but prolonged the sodium current inactivation time constant. Estradiol decreased the persistent sodium current amplitude, and induced a significant negative shift in peak current potential. In contrast to results obtained from cells from young reproductive animals, estradiol did not significantly attenuate the sodium current underlying the action potential in cells isolated from middle-aged or old mice. Sodium channels can modulate cell threshold, latency of firing, and action potential characteristics. The reduction of sodium current amplitude by estradiol suggests a negative feedback on GnRH neurons, which could lead to a downregulation of cell excitability and hormone release. The attenuation of estradiol regulation in peripostreproductive and postreproductive animals could lead to dysregulated hormone release with advancing age. PMID- 20580638 TI - Dimerization drives PDGF receptor endocytosis through a C-terminal hydrophobic motif shared by EGF receptor. AB - Like many other receptor tyrosine kinases (RTKs), platelet-derived growth factor (PDGF) receptor beta (PDGFR-beta) is internalized and degraded in lysosomes in response to PDGF stimulation, which regulates many aspects of cell signalling. However, little is known about the regulation of PDGFR-beta endocytosis. Given that ligand binding is essential for the rapid internalization of RTKs, the events induced by the ligand binding likely contribute to the regulation of ligand-induced RTK internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosphorylation. In this communication, we examined the role of PDGFR-beta kinase activity, PDGFR-beta dimerization and PDGFR-beta C-terminal motifs in PDGF-induced PDGFR-beta internalization. We showed that inhibition of PDGFR-beta kinase activity by chemical inhibitor or mutation did not block PDGF-induced PDGFR-beta endocytosis, suggesting that the kinase activity is not essential. We further showed that dimerization of PDGFR-beta is essential and sufficient to drive PDGFR-beta internalization independent of PDGFR-beta kinase activation. Moreover, we showed that the previously reported 14 amino acid sequence 952-965 is required for PDGF induced PDGFR-beta internalization. Most importantly, we showed that this PDGFR beta internalization motif is exchangeable with the EGFR internalization motif (1005-1017) in mediating ligand-induced internalization of both PDGFR-beta and EGFR. This indicates a common mechanism for the internalization of both PDGFR beta and EGFR. PMID- 20580639 TI - Correcting diastolic dysfunction by Ca2+ desensitizing troponin in a transgenic mouse model of restrictive cardiomyopathy. AB - Several cardiac troponin I (cTnI) mutations are associated with restrictive cardiomyopathy (RCM) in humans. We have created transgenic mice (cTnI(193His) mice) that express the corresponding human RCM R192H mutation. Phenotype of this RCM animal model includes restrictive ventricles, biatrial enlargement and sudden cardiac death, which are similar to those observed in RCM patients carrying the same cTnI mutation. In the present study, we modified the overall cTnI in cardiac muscle by crossing cTnI(193His) mice with transgenic mice expressing an N terminal truncated cTnI (cTnI-ND) that enhances relaxation. Protein analyses determined that wild type cTnI was replaced by cTnI-ND in the heart of double transgenic mice (Double TG), which express only cTnI-ND and cTnI R193H in cardiac myocytes. The presence of cTnI-ND effectively rescued the lethal phenotype of RCM mice by reducing the mortality rate. Cardiac function was significantly improved in Double TG mice when measured by echocardiography. The hypersensitivity to Ca(2+) and the prolonged relaxation of RCM cTnI(193His) cardiac myocytes were completely reversed by the presence of cTnI-ND in RCM hearts. The results demonstrate that myofibril hypersensitivity to Ca(2+) is a key mechanism that causes impaired relaxation in RCM cTnI mutant hearts and Ca(2+) desensitization by cTnI-ND can correct diastolic dysfunction and rescue the RCM phenotypes, suggesting that Ca(2+) desensitization in myofibrils is a therapeutic option for treatment of diastolic dysfunction without interventions directed at the systemic beta-adrenergic-PKA pathways. PMID- 20580640 TI - Tumour suppression by immune system through stochastic oscillations. AB - The well-known Kirschner-Panetta model for tumour-immune System interplay [Kirschner, D., Panetta, J.C., 1998. Modelling immunotherapy of the tumour-immune interaction. J. Math. Biol. 37 (3), 235-252] reproduces a number of features of this essential interaction, but it excludes the possibility of tumour suppression by the immune system in the absence of therapy. Here we present a hybrid stochastic version of that model. In this new framework, we show that in reality the model is also able to reproduce the suppression, through stochastic extinction after the first spike of an oscillation. PMID- 20580641 TI - The relation between anger and different forms of disgust: implications for emotion recognition impairments in Huntington's disease. AB - Initial reports of emotion recognition in Huntington's disease (HD) found disproportionate impairments in recognising disgust. Not all subsequent studies have found this pattern, and a review of the literature to date shows that marked impairments in recognising anger are also often seen in HD. However, the majority of studies have based their conclusions on a single test of facial expression recognition. In the current study we revisit this issue of emotion recognition in HD to address whether the pattern found on one test of facial expression recognition generalised to another, and to different modalities using tests of emotion recognition from facial expressions, vocal expressions, and short verbal vignettes. The results showed evidence of impairments in recognising anger, fear and disgust across the three domains, with recognition of anger the most severely impaired. Given work identifying different subtypes of disgust that are associated with different facial features, a second study examined the recognition of three disgust expressions that healthy participants reliably associate with unpleasant tastes, unpleasant smells, and a more general elaborated or expanded form of disgust that includes reactions to violations of moral standards. The results showed a disproportionate impairment in recognising faces associated with the expanded form, the subtype most closely aligned with anger. We conclude that the related emotions of disgust and anger associated with social disapproval are frequently impaired in HD and discuss factors that might cause one emotion to show more severe impairments than the other. PMID- 20580642 TI - Pattern of biphasic response to various noxious stimuli in rats ingesting sucrose ad libitum. AB - Sucrose ingestion is reported to produce an initial (20-30min) analgesia and late (<5h) hyperalgesia. However, the influence of the characteristics of noxious stimuli and sweet substances on the pattern of transition from analgesia to hyperalgesia is not known. Therefore, we investigated the effect of sucrose (20%, sucrose fed group), saccharin (0.1%, saccharin fed group) and water ingestion (control group) on pain responses to various noxious stimuli for 5h. Latency of motor response of tail (TFL), paws to noxious thermal stimuli, threshold for elicitation of motor responses to electrical stimulation of tail nociceptive afferents in 5 sessions (0, 0.25, 1, 3 and 5h) and pain-related behavior to tonic noxious stimulus in 3 sessions at 1, 3 and 5h were recorded. In sucrose fed rats as compared to controls, the TFL sequentially increased (9.29+/-0.47s from 8.41+/ 0.25; p<0.01), recovered to base-line and decreased (6.61+/-0.61sec; p<0.0001) in sessions II, III and V indicating analgesia, eualgesia and hyperalgesia, respectively. In saccharin fed rats the initial analgesia extended until session III followed by eualgesia and hyperalgesia in sessions IV and V. Pain related behaviour to tonic noxious stimulus also indicated an initial analgesia (0-5min), intermediate eualgesia and late hyperalgesia (3-5h) in sucrose fed rats, whereas only analgesia in saccharin fed rats. The results of our study suggest that sucrose ingestion for 5h leads to a bi-phasic response to both phasic and tonic noxious stimuli, albeit there are variations in their durations. Therefore, the temporal relationship of the nociceptive responses to palatable food is a function of the stimulus quality of both. PMID- 20580643 TI - Statistical regularities in art: Relations with visual coding and perception. AB - Since at least 1935, vision researchers have used art stimuli to test human response to complex scenes. This is sensible given the "inherent interestingness" of art and its relation to the natural visual world. The use of art stimuli has remained popular, especially in eye tracking studies. Moreover, stimuli in common use by vision scientists are inspired by the work of famous artists (e.g., Mondrians). Artworks are also popular in vision science as illustrations of a host of visual phenomena, such as depth cues and surface properties. However, until recently, there has been scant consideration of the spatial, luminance, and color statistics of artwork, and even less study of ways that regularities in such statistics could affect visual processing. Furthermore, the relationship between regularities in art images and those in natural scenes has received little or no attention. In the past few years, there has been a concerted effort to study statistical regularities in art as they relate to neural coding and visual perception, and art stimuli have begun to be studied in rigorous ways, as natural scenes have been. In this minireview, we summarize quantitative studies of links between regular statistics in artwork and processing in the visual stream. The results of these studies suggest that art is especially germane to understanding human visual coding and perception, and it therefore warrants wider study. PMID- 20580644 TI - Age-related changes in visual temporal order judgment performance: Relation to sensory and cognitive capacities. AB - Five measures of temporal order judgments were obtained from 261 participants, including 146 elder, 44 middle aged, and 71 young participants. Strong age group differences were observed in all five measures, although the group differences were reduced when letter discriminability was matched for all participants. Significant relations were found between these measures of temporal processing and several cognitive and sensory assays, and structural equation modeling revealed the degree to which temporal order processing can be viewed as a latent factor that depends in part on contributions from sensory and cognitive capacities. The best-fitting model involved two different latent factors representing temporal order processing at same and different locations, and the sensory and cognitive factors were more successful predicting performance in the different location factor than the same-location factor. Processing speed, even measured using high-contrast symbols on a paper-and-pencil test, was a surprisingly strong predictor of variability in both latent factors. However, low level sensory measures also made significant contributions to the latent factors. The results demonstrate the degree to which temporal order processing relates to other perceptual and cognitive capacities, and address the question of whether age-related declines in these capacities share a common cause. PMID- 20580645 TI - Extraction and antioxidant activities of intracellular polysaccharide from Pleurotus sp. mycelium. AB - The extraction conditions of intracellular polysaccharide (IPS) from Pleurotus sp. mycelium in submerged culture were investigated. Four parameters affecting the IPS extraction, ultrasonic treatment time, extraction temperature, extraction time and ethanol concentration, were determined by single factor tests and then optimized by orthogonal experiments. Under the optimized conditions, the extraction rates of IPS of Pleurotus nebrodensis SJ-02, Pleurotus eryngii SI-01 and Pleurotus corncopiae SS-01 were 7.1+/-0.4%, 7.5+/-0.3%, and 8.2+/-0.5%, respectively. The in vitro hydroxyl radical inhibition percentages of IPS of three mushrooms were 32.2+/-2.8%, 16.1+/-1.5%, and 38.7+/-3.1%, respectively. The scavenging effects of IPS on superoxide anion radical and 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical were 19.1+/-1.5%, 16.3+/-1.3%, 20.3+/-1.8%, 17.9+/ 1.6%, 16.8+/-1.4%, and 20.5+/-1.7%, respectively. The results provide a reference for large-scale production of IPS by Pleurotus sp. in industrial fermentation. PMID- 20580646 TI - A brain-computer interface method combined with eye tracking for 3D interaction. AB - With the recent increase in the number of three-dimensional (3D) applications, the need for interfaces to these applications has increased. Although the eye tracking method has been widely used as an interaction interface for hand disabled persons, this approach cannot be used for depth directional navigation. To solve this problem, we propose a new brain computer interface (BCI) method in which the BCI and eye tracking are combined to analyze depth navigation, including selection and two-dimensional (2D) gaze direction, respectively. The proposed method is novel in the following five ways compared to previous works. First, a device to measure both the gaze direction and an electroencephalogram (EEG) pattern is proposed with the sensors needed to measure the EEG attached to a head-mounted eye tracking device. Second, the reliability of the BCI interface is verified by demonstrating that there is no difference between the real and the imaginary movements for the same work in terms of the EEG power spectrum. Third, depth control for the 3D interaction interface is implemented by an imaginary arm reaching movement. Fourth, a selection method is implemented by an imaginary hand grabbing movement. Finally, for the independent operation of gazing and the BCI, a mode selection method is proposed that measures a user's concentration by analyzing the pupil accommodation speed, which is not affected by the operation of gazing and the BCI. According to experimental results, we confirmed the feasibility of the proposed 3D interaction method using eye tracking and a BCI. PMID- 20580647 TI - Paraffin-embedded tissue (PET) blot method: application to Alzheimer disease. AB - Traditionally, immunohistochemistry, immunoblotting, and histoblot have been used to detect protein in tissue samples. However, each of these techniques has a number of disadvantages. The sensitivity of protein detection in immunohistochemistry is lost due to fixation or paraffin embedding methods that modify antigenic sites. The anatomical resolution and specific cellular involvement are lost in immunoblotting. Histoblot, a hybrid of these two techniques, is able to resolve these issues, but it cannot be applied to formalin fixed tissues. A recent technique, paraffin-embedded tissue (PET) blot, retains the superior protein detection and anatomical resolution of histoblot and is applicable to formalin-fixed tissues. Unfortunately, a major obstacle to the widespread application of PET is the lack of a detailed methodological description. In this paper, we describe a PET blotting method that was formulated from our own empirical and experimental research in Alzheimer disease and a systematic review of the current literature. From this, we conclude that PET can be applied to a variety of conditions with a wide spectrum of pathology. PMID- 20580648 TI - Stress inoculation facilitates active avoidance learning of the semi-precocial rodent Octodon degus. AB - A growing body of evidence highlights the impact of the early social environment for the adequate development of brain and behavior in animals and humans. Disturbances of this environment were found to be both maladaptive and adaptive to emotional and cognitive function. Using the semi-precocial, biparental rodent Octodon degus, we aimed to examine (i) the impact of age (juvenile/adult), sex (male/female), and (ii) "motivation" to solve the task (by applying increasing foot-shock-intensities) on two-way active avoidance (TWA) learning in socially reared degus, and (iii) whether early life stress inoculation by 1h daily parental separation during the first three weeks of life has maladaptive or adaptive consequences on cognitive function as measured by TWA learning. Our results showed that (i) juvenile degus, unlike altricial rats of the same age, can successfully learn the TWA task comparable to adults, and (ii) that learning performance improves with increasing "task motivation", irrespective of age and sex. Furthermore, we revealed that (iii) stress inoculation improves avoidance learning, particularly in juvenile males, quantitatively and qualitatively depending on "task motivation". In conclusion, the present study describes for the first time associative learning in O. degus and its modulation by early life stress experience as an animal model to study the underlying mechanisms of learning and memory in the stressed and unstressed brain. Although, stress is commonly viewed as being maladaptive, our data indicate that early life stress inoculation triggers developmental cascades of adaptive functioning, which may improve cognitive and emotional processing of stressors later in life. PMID- 20580649 TI - Increased depressive behaviour in mice harboring the mutant thyroid hormone receptor alpha 1. AB - Clinical evidence indicates that hypothyroidism contributes to mood disorders. The present study tested if the mutant thyroid hormone receptor alpha 1 (TRalpha1) that causes a receptor-mediated hypothyroidism in the brain affects depressive and anxious behaviour in mice. Mice heterozygous for the TRalpha1 allele (TRalpha1+/m), yielding a receptor protein with a 10-fold reduced affinity to triiodothyronine (T3), and wildtype (wt) mice were subjected to several paradigms specifically testing depressive and anxious behaviour. Mutant and wt mice were either treated with T3 or vehicle. Untreated TRalpha1+/m animals displayed reduced locomotion, higher rates of helplessness in the shuttle box-, greater levels of anxiety in the startle response- and dark light box behavioural paradigms when compared to wt mice. Continuous T3-substitution therapy was effective in alleviating anxious and depressive behaviour without affecting locomotion in mutant mice. Notably, continuous T3-substitution reduced overall locomotion and increased helpless behaviour in wt mice when compared to untreated wt mice. The data suggest that receptor-mediated hypothyroidism caused by an unliganded thyroid hormone receptor alpha 1 leads to a depressive and anxious phenotype in mice, which is responsive to continuous T3-substitution and that an iatrogeneously induced hyperthyreoidism by continuous T3-administration leads to a hypolocomotive and depressive phenotype. PMID- 20580650 TI - Arp1, an actin-related protein, in Plasmodium berghei. AB - Actin-related proteins (Arps) constitute a family of eukaryotic cytoskeletal proteins involved in such diverse events as cell motility, cytokinesis, vesicle transport, and chromatin remodelling. Previously, in a study of Plasmodium berghei gene expression in ookinetes and oocysts, we detected stage-specific increased expression of a gene encoding an Arp. Here we further characterize this gene and the encoded protein. We present a phylogenetic and three-dimensional modelling analysis as well as cell biological and genetic data that support classification of this gene as being an orthologue of the actin-related protein 1 (Arp1). This gene was found to be expressed in asexual stages as well as in the mosquito stages of the parasite, both on the transcript and protein level. Our attempts to delete the gene in the parasite for functional studies were unsuccessful, suggesting that it may be essential. The protein was localized apically of the nucleus in ookinetes, and in combination with the known function of Arp1 proteins, this suggests a role in vesicular transport. Expression of the gene in Saccharomyces cerevisiae resulted in toxic effects and interference with the yeast cytoskeleton. PMID- 20580652 TI - Isolation and characterization of cytotoxic cyclotides from Viola tricolor. AB - Many plants of the Violaceae plant family have been used in traditional remedies, and these plants often contain cyclotides, a particular type of plant cyclopeptide that is distinguished by a cyclic cystine knot motif. In general, bioactive plant cyclopeptides are interesting candidates for drug development. In the current study, a suite of 14 cyclotides, which includes seven novel cyclotides [vitri B, C, D, E, F, varv Hm, and He], together with seven known cyclotides [varv A, D, E, F, H, vitri A, and cycloviolacin O2], was isolated from Viola tricolor, a common flower. A chromatography-based method was used to isolate the cyclotides, which were characterized using tandem mass spectrometry and NMR spectroscopy. Several of the cyclotides showed cytotoxic activities against five cancer cell lines, U251, MDA-MB-231, A549, DU145, and BEL-7402. Three cyclotides, vitri A, vitri F, and cycloviolacin O2, were the most cytotoxic. The cytotoxic activity of the cyclotides did not correlate well with their hemolytic activity, indicating that different interactions, most likely with membranes, are involved for cytotoxic and hemolytic activities. Homology modeling of the structures was used in deriving structure-activity relationships. PMID- 20580651 TI - Nesfatin-1--role as possible new potent regulator of food intake. AB - Nesfatin-1 is an 82 amino acid peptide recently discovered in the brain which is derived from nucleobindin2 (NUCB2), a protein that is highly conserved across mammalian species. Nesfatin-1 has received much attention over the past two years due to its reproducible food intake-reducing effect that is linked with recruitment of other hypothalamic peptides regulating feeding behavior. A growing amount of evidence also supports that various stressors activate fore- and hindbrain NUCB2/nesfatin-1 circuitries. In this review, we outline the central nervous system distribution of NUCB2/nesfatin-1, and recent developments on the peripheral expression of NUCB2/nesfatin-1, in particular its co-localization with ghrelin in gastric X/A-like cells and insulin in ss-cells of the endocrine pancreas. Functional studies related to the characteristics of nesfatin-1's inhibitory effects on dark phase food intake are detailed as well as the central activation of NUCB2/nesfatin-1 immunopositive neurons in the response to psychological, immune and visceral stressors. Lastly, potential clinical implications of targeting NUCB2/nesfatin-1 signaling and existing gaps in knowledge to ascertain the role and mechanisms of action of nesfatin-1 are presented. PMID- 20580653 TI - Identification of E. dysenterica laxative peptide: a novel strategy in the treatment of chronic constipation and irritable bowel syndrome. AB - Plants have contributed over the years to the discovery of various pharmacological products. Amongst the enormous diversity of herbs with remarkable medicinal use and further pharmacological potential, here in this report we evaluated pulp extracts from Eugenia dysenterica fruits and further identified the active principle involved in such laxative activity in rats. For protein isolation, fruits were macerated with an extraction solution following precipitation with (NH(4))(2)SO(4) (100%). After dialysis, the peptide was applied onto a reversed-phase semi-preparative HPLC column, and the major fraction was eluted with 26% and 66% acetonitrile. The evaluation of molecular masses by MALDI-TOF and Tris/Tricine SDS-PAGE of HPLC fractions showed the presence of a major peptide with approximately 7 kDa. The N-terminal amino acid peptide sequence was determined and showed no similarity to other proteins deposited in the Data Bank. Peptide from E. dysenterica was able to enhance rats' intestinal motility by approximately 20.8%, probably being responsible for laxative activity. Moreover, these proteins were non-toxic to mammals, as observed in histopathology and hemolytic analyses. In conclusion, results here reported indicate that, in the near future, proteins synthesized by E. dysenterica fruits could be utilized in the development of novel biotechnological pharmaceutics with laxative properties for use in chronic constipation and irritable bowel syndrome treatment. PMID- 20580654 TI - Association of killer cell immunoglobulin-like receptors and human leukocyte antigen-C genotypes in South Brazilian with type 1 diabetes. AB - Type 1 diabetes mellitus (T1D) is a multifactorial and chronic autoimmune disease caused by the deficiency of insulin synthesis and or by its secretion or action defects. Genetic and environmental factors are known to be involved in its pathogenesis. The human leukocyte antigen complex (human leukocyte antigen (HLA)) constitutes the most relevant region contributing with 50% of the inherited risk for T1D. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer immunoglobulin-like receptors (KIR). The aim of our study is to evaluate the association between the KIR genes and HLA alleles in patients with T1D and healthy controls. Two hundred forty-eight T1D patients and 250 healthy controls were typed for HLA and KIR genes by PCR-SSP. Our results showed an increase of C2 in controls (p = 0.002). The genotype 2DL1/C2+ was also more common in controls (p = 0.001), as well as haplotype association KIR2DL2/DR3/DR4+ and the combination with only DR3+ (p < 0.001; p < 0.001). The maximum protection was seen when KIR2DL2/DR3-were absent when the combination of KIR2DL1/C2+ were present (p < 0.001) and the maximum risk was observed when KIR2DL2/DR3/DR4+ were present in the absence of KIR2DL1/C2- (p = 0.005). Our results confirmed the association of the KIR2DL2/DR3 increasing risk for T1D and suggest a protective role of KIR2DL1/C2. PMID- 20580657 TI - Effects of Eucommia leaf extracts on autonomic nerves, body temperature, lipolysis, food intake, and body weight. AB - Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes. PMID- 20580658 TI - Crossmodal facilitation of masked visual target discrimination by informative auditory cuing. AB - Temporally synchronous, auditory cues can facilitate participants' performance on dynamic visual search tasks. Making auditory cues spatially informative with regard to the target location can reduce search latencies still further. In the present study, we investigated how multisensory integration, and temporal and spatial attention, might conjointly influence participants' performance on an elevation discrimination task for a masked visual target presented in a rapidly changing sequence of masked visual distractors. Participants were presented with either spatially uninformative (centrally presented), spatially valid (with the target side), or spatially invalid tones that were synchronous with the presentation of the visual target. Participants responded significantly more accurately following the presentation of the spatially valid as compared to the uninformative or invalid auditory cues. Participants endogenously shifted their attention to the likely location of the target indicated by the valid spatial auditory cue (reflecting top-down, cognitive processing mechanisms), which facilitated their processing of the visual target over and above any bottom-up benefits associated solely with the synchronous presentation of the auditory and visual stimuli. The results of the present study therefore suggest that crossmodal attention (both spatial and temporal) and multisensory integration can work in parallel to facilitate people's ability to most efficiently respond to multisensory information. PMID- 20580656 TI - E2F1 localizes predominantly to neuronal cytoplasm and fails to induce expression of its transcriptional targets in human immunodeficiency virus-induced neuronal damage. AB - As human immunodeficiency virus (HIV) does not induce neuronal damage by direct infection, the mechanisms of neuronal damage or loss in HIV-associated dementia (HAD) remain unclear. We have shown previously that immunoreactivity of transcription factor, E2F1, increases in neurons, localizing predominantly to the cytoplasm, in HIV-associated pathologies. Here we confirm that E2F1 localization is predominantly cytoplasmic in primary postmitotic neurons in vitro and cortical neurons in vivo. To determine whether E2F1 contributes to neuronal death in HAD via transactivation of target promoters, we assessed the mRNA and protein levels of several classical E2F1 transcriptional targets implicated in cell cycle progression and apoptosis in an in vitro model of HIV-induced neurotoxicity and in cortical autopsy tissue from patients infected with HIV. By Q-PCR, we show that mRNA levels of E2F1 transcriptional targets implicated in cell cycle progression (E2F1, Cyclin A, proliferating cell nuclear antigen (PCNA), and dyhydrofolate reductase (DHFR)) and apoptosis (caspases 3, 8, 9 and p19(ARF)) remain unchanged in an in vitro model of HIV-induced neurotoxicity. Further, we show that protein levels of p19(ARF), Cyclin A, and PCNA are not altered in vitro or in the cortex of patients with HAD. We propose that the predominantly cytoplasmic localization of E2F1 in neurons may account for the lack of E2F1 target transactivation in neurons responding to HIV-induced neurotoxicity. PMID- 20580659 TI - Peripheral and central cyclooxygenase (COX) products may contribute to the manifestation of brain-controlled sickness responses during localized inflammation induced by macrophage-activating lipopeptide-2 (MALP-2). AB - We investigated whether an inflammation-dependent activation of the brain occurs in response to systemic intraperitoneal (i.p.) or local injections of macrophage activating lipopeptide-2 (MALP-2) into a subcutaneous (s.c.) air pouch, and whether local (peripheral) or central cyclooxygenase (COX)-2-dependent formations of prostaglandin E(2) (PGE(2)) are involved in MALP-2-induced illness responses. Body temperature, activity, food and water intake were measured telemetrically. Local (s.c.) and circulating levels of PGE(2) were measured by an ELISA. Inflammatory activation of the brain in response to MALP-2 was determined by immunohistochemical detection of the transcription factors NFkappaB and STAT3 in cell nuclei as well as the appearance of COX-2 at the same sites. S.c. treatment with the preferential COX-2 inhibitor meloxicam attenuated, but not abolished fever induced by local injections of MALP-2 into the pouch. Local MALP-2-induced formation of PGE(2) was blunted by treatment with meloxicam. In the brain, i.p. stimulation with MALP-2-induced nuclear STAT3- and NFkappaB-translocation in the vasculature and the sensory circumventricular organs, which was accompanied by an increase in COX-2 immunoreactivity (IR) in endothelial cells. Local MALP-2 treatment induced a moderate STAT3 activation and a small but significant increase in COX-2 IR while no NFkappaB-activation could be observed in the brains of these animals. We demonstrated that the activation of the brain STAT3 (NFkappaB)-COX-2 singling cascade seems to be involved in the manifestation of brain-controlled illness symptoms induced by systemic and local inflammatory stimulation with MALP-2. The present data further suggest a contribution of peripherally produced PGE(2) to MALP-2-induced activation of brain sites implicated in fever. PMID- 20580660 TI - Oxytocin and same-sex social behavior in female meadow voles. AB - The neuropeptide oxytocin (OT) has been implicated in a range of mammalian reproductive and social behaviors including parent-offspring bonding and partner preference formation between socially monogamous mates. Its role in mediating non reproductive social relationships in rodents, however, remains largely unexplored. We examined whether OT facilitates same-sex social preferences between female meadow voles-a species that forms social nesting groups in short, winter-like day lengths. In contrast to results from studies of opposite-sex attachment between prairie vole mates, we found that neither OT nor dopamine neurotransmission was required for baseline levels of social partner preference formation or expression. OT enhanced preference formation beyond baseline levels an effect that was counteracted by treatment with an oxytocin receptor antagonist (OTA). Oxytocin receptor (OTR) density correlated with social behavior in brain regions not known to be associated with opposite-sex affiliation, including the lateral septum and central amygdala. In addition, voles housed in short day lengths (SD) exhibited higher levels of OTR binding in the central amygdala, and voles exposed to high concentrations of estradiol exhibited less binding in the nucleus accumbens (NAcc) and increased binding in the ventromedial nucleus of the hypothalamus. These results suggest that same-sex social behavior shares common elements with other mammalian social behaviors affected by OT, but that the specific neural pathways through which OT exerts its influence are likely distinct from those known for sexual attachments. PMID- 20580661 TI - Effects of a new potent analog of tocainide on hNav1.7 sodium channels and in vivo neuropathic pain models. AB - The role of voltage-gated sodium channels in the transmission of neuropathic pain is well recognized. For instance, genetic evidence recently indicate that the human Nav1.7 sodium channel subtype plays a crucial role in the ability to perceive pain sensation and may represent an important target for analgesic/anti hyperalgesic drugs. In this study a newly synthesized tocainide congener, named NeP1, was tested in vitro on recombinant hNav1.4 and hNav1.7 channels using patch clamp technique and, in vivo, in two rat models of persistent neuropathic pain obtained either by chronic constriction injury of the sciatic nerve or by oxaliplatin treatment. NeP1 efficiently blocked hNav1.4 and hNav1.7 channels in a dose- and use-dependent manner, being by far more potent than tocainide. Importantly, the new compound displayed a remarkable use-dependent effect, which likely resulted from a very high affinity for inactivated compared to closed channels. In both models of neuropathic pain, NeP1 was greatly more potent than tocainide in reverting the reduction of pain threshold in vivo. In oxaliplatin treated rats, NeP1 even produced greater and more durable anti-hyperalgesia than the reference drug tramadol. In addition, in vivo and in vitro studies suggest a better toxicological and pharmacokinetic profile for NeP1 compared to tocainide. Overall, these results indicate NeP1 as a new promising lead compound for further development in the treatment of chronic pain of neuropathic origin. PMID- 20580662 TI - Antispasmodic and antioxidant activities of fractions and bioactive constituent davidigenin isolated from Mascarenhasia arborescens. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mascarenhasia arborescens A. DC. (Apocynaceae) is used in traditional medicine in the North of Madagascar to treat intestinal disorders, intestinal spasms and diarrhoea. AIM OF THE STUDY: The main objective of this work was to evaluate the antispasmodic activity of the crude methanolic extract of Mascarenhasia arborescens and of its four partitions and to identify the effective compound responsible for this effect. MATERIALS AND METHODS: Isolation and structure elucidation techniques were performed in order to identify the bioactive constituent of Mascarenhasia arborescens and HPLC analysis was used for its quantification. Total phenolic content (TPC) of crude extracts and partitions were determined using the Folin-Ciocalteu method. Crude methanolic extract, partitions and the bioactive compound were investigated for their spasmolytic activity on several isolated organs. Their antiradical activity was also investigated by the DPPH test. RESULTS: Bioassay-guided fractionation using isolated guinea pig ileum pre-contracted with histamine 3x10(-6) M led to the isolation of davidigenin (DG), a dihydrochalcone, as the main active constituent from the most promising methylene chloride partition (McP). This partition was effective on isolated guinea pig ileum pre-contracted with 3x10(-6) M histamine, with a median effective concentration (EC(50)) of 41.19+/-3.74 microg/ml. The DG content of this partition was shown to be 26.5% by HPLC. DG induced a concentration-dependent relaxation of the histamine pre-contracted guinea pig ileum with an EC(50) of 8.04+/-0.81 microg/ml and a concentration-dependent relaxation of the acetylcholine pre-contracted rat duodenum with an EC(50) of 9.35+/-0.30 microg/ml. It inhibited in a non-competitive manner histamine-induced isolated ileum contraction and the acetylcholine-induced isolated duodenum contraction. Moreover, DG does not have any antiradical activity. CONCLUSIONS: We demonstrated for the first time antispasmodic and antioxidant effects of Mascarenhasia arborescens. This study supports its use in traditional medicine. Furthermore, we highlighted the crucial role of davidigenin in the antispasmodic activity of this plant. PMID- 20580663 TI - Cadmium chloride alters mRNA levels of angiogenesis related genes in primary human endometrial endothelial cells grown in vitro. AB - Cadmium, is known to cause adverse reproductive effects, and classified as an endocrine disrupting chemical (EDC). Human endometrial endothelial cells (HEEC) have a key role in the regulation of endometrial angiogenesis. These cells are known to express estrogen receptors, a feature that makes them potential targets for EDCs such as cadmium. We have designed a co-culture system, in which HEEC were grown in the same cell culture medium as endometrial stromal cells but in separate, communicating chambers. With quantitative PCR, we investigated changes in mRNA expression of genes associated with angiogenesis, sex steroids and endothelial cell specific functions. We found that cadmium altered the mRNA expression of the two important angiogenic molecules VEGF-A and PLGF. Cadmium might thus affect endometrial angiogenesis and as a consequence cause endometrial dysfunction with an increased risk for fertility problems. PMID- 20580664 TI - Role of dietary GSH in the amelioration of sodium arsenite-induced ovarian and uterine disorders. AB - The study investigated whether dietary reduced glutathione (GSH) could be useful in alleviating arsenic-induced female gonadal injury in Wistar rats. Ingestion of sodium arsenite contaminated water (0.4 ppm) to Wistar rats for seven estrous cycles (28 days) significantly diminished ovarian key steroidogenic enzymes activities and gonadotrophins and estradiol signaling along with disrupted ovarian and uterine growth. Oxidative stress as well as histological distortion of ovarian and uterine tissue was prominent along with prolonged diestrus in arsenic-exposed rats. Decreased levels of dopamine (DA) and norepinephrine (NE) and elevated level of 5-hydroxytryptamine (5-HT) in midbrain and diencephalons were also evident following arsenic exposure. All these deleterious effects of arsenic ingestion were mitigated by administration of GSH (8.0mg/100g body weight/day). Only tissue deposition of arsenic appeared to be unaffected by dietary GSH. The study highlighted that co-administration of GSH could ameliorate arsenic-mediated injuries of female reproductive organs. PMID- 20580665 TI - Reproductive Toxicology. Editorial. PMID- 20580666 TI - Effects of PFNA exposure on expression of junction-associated molecules and secretory function in rat Sertoli cells. AB - Perfluorononanoic acid (PFNA, C9), a synthetic perfluorinated chemical containing nine carbons, has been identified in humans and wildlife worldwide. Sertoli cell plays a key role in spermatogenesis; however, the toxic effects of PFNA on Sertoli cells have not been studied. The aim of this study was to investigate the effects of PFNA exposure on cell junction molecules and factors specifically secreted by Sertoli cells. Primary Sertoli cells from 20- to 21-day-old rats were exposed to increasing PFNA concentrations (0, 1, 10, 25, 50, or 75 MUM) for 24h. No significant changes in the expression of cytoskeleton-associated molecules were noted, although the mRNA levels of vimentin were upregulated dramatically in cells exposed to 50 and 75 MUM PFNA. Meanwhile, the mRNA levels of Sertoli cell specific secretions, such as Mullerian inhibiting substance (MIS), androgen binding protein (ABP), inhibin B, transferrin, and follicle-stimulating hormone receptor (FSH-R) changed significantly in experimental groups. Wilms' tumor gene (WT1), a transcription factor, was upregulated significantly in cells exposed to 1-75 MUM PFNA. In additional studies, male rats were exposed to 0, 1, 3, or 5mg/kg-d PFNA for 14 days. Vacuoles in the cytoplasm of Sertoli cells were observed in the ultrastructure of testis. Furthermore, the changes in the concentrations of MIS and inhibin B in serum and the protein levels of WT1 and transferrin in testis were similar to the mRNA expression levels of those observed after in vitro treatment. In conclusion, these findings demonstrated that PFNA treatment led to the damage of specific secretory functions of Sertoli cells and that these effects might be an underlying cause of the male-specific reproductive toxicity of PFNA. PMID- 20580668 TI - CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats. AB - Retinoids are essential in vertebrate reproduction and embryonic development. All trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17betaHSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation. PMID- 20580667 TI - Organochlorine pesticides and endometriosis. AB - Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20 cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR=5.3; 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings. PMID- 20580669 TI - Development of amphotericin B loaded polymersomes based on (PEG)(3)-PLA co polymers: Factors affecting size and in vitro evaluation. AB - Amphotericin B (AmB) is a broad spectrum antifungal and antileishmenial agent and its clinical use is limited due to substantial dose limiting toxicities such as nephrotoxicity. In this work, amphotericin B is formulated in polymersomes of branched (PEG)(3)-PLA co-polymer. Polymersomes were prepared by solvent injection method and the effects of various formulation and process parameters on size and size distribution were studied. The results showed that viscosity of biphasic solution during formulation has significant influence on the size and size distribution of the polymersomes. Further, drug-loaded polymersomes with size of 199.6+/-14.1nm, PDI of 0.258+/-0.18, zeta potential (zeta) of -18.07+/-4.91mV and loading of 16.26+/-2.50% were obtained. Drug was found to be intercalated in the wall of polymersomes as observed using FITC tagged drug and CLSM study. An in vitro release media containing sodium deoxycholate was developed and a significant amount of drug release was observed up to 24h there after a very slow release was obtained. Free drug was not found in the formulation and different molecular forms of the drug (AmB) were observed by UV-visible spectroscopy and circular dichroism. This was further supported by hemolysis experiments, where negligible hemolysis in the test formulation was observed as compared to 100% hemolysis in a marketed formulation (Fungizone). PMID- 20580670 TI - On the search for in vitro in vivo correlations in the field of intra-articular drug delivery: administration of sodium diatrizoate to the horse. AB - Development of suitable in vitro release models for formulation development as well as quality control purposes has to be initiated in the early design phase of injectable depots. Optimally, construction of an in vitro release model may lead to the establishment of in vitro in vivo correlations. By using a model compound (sodium diatrizoate, DTZ), the purpose of this study was to investigate the possibility of establishing in vitro in vivo relations between the DTZ disappearance profile obtained from the donor compartment of the rotating dialysis cell model and the joint disappearance profile following intra-articular administration. In vitro experiments were conducted by applying solutions of DTZ to the donor compartment. In the in vivo experiments, five horses were subjected to both intravenous and intra-articular administration of an aqueous solution of 3.9 mg DTZ/kg. A strong relation (R(2)=0.99) was obtained between the disappearance data from the donor compartment of the in vitro model and the disappearance data from the synovial fluid after intra-articular administration of DTZ. Furthermore, a relation (R(2)=0.91) between the appearance data obtained from the acceptor compartment and the deconvolved appearance serum data upon intra-articular administration of DTZ was obtained. The correlations obtained in this study hold promise that the rotating dialysis cell model has a role in the prediction of the intra-articular fate of drugs injected as solutions. PMID- 20580671 TI - Intestinal permeability enhancement of levothyroxine sodium by straight chain fatty acids studied in MDCK epithelial cell line. AB - Levothyroxine sodium (T4), administered orally, is used for the treatment of hypothyroidism. T4 is a narrow therapeutic index drug with highly variable bioavailability (40-80%). The purpose of the present study was to increase the transepithelial transport of T4 using straight chain fatty acids across Madin Darby Canine kidney (MDCK) cell line. Capric acid (C10), lauric acid (C12) and oleic acid (C18) were studied in molar ratios of 1:0.5, 1:1, 1:2 and 1:3 (T4:fatty acid). Transport of the hydrophilic marker, Lucifer yellow, was also studied. All three fatty acids proved to significantly increase T4 transport and the order of enhancement was to the effect of C12 approximately C18>C10. This Increase in transport was accompanied by reductions in transepithelial electrical resistance (TEER) values, which indicates an opening of tight junctions. Cytotoxic effects of the fatty acids were evaluated by TEER measurements, lactate dehydrogenase release, percent viability and propidium iodide staining of the cells. At the lower molar concentrations of 1:1, the fatty acids did not show any toxicity. However, C12 and C18 when added, to T4:fatty acid molar ratio of 1:2 and 1:3, respectively showed severe toxicity with irreversible damage to the cells. Hence, addition of fatty acids to T4 formulations at low concentrations can significantly improve intestinal permeability of T4 without any toxicity potentially leading to improved bioavailability. PMID- 20580672 TI - Quercetin enhances adiponectin secretion by a PPAR-gamma independent mechanism. AB - To study possible insulin sensitizing, anti-inflammatory and anti-oxidative effects of the flavonol quercetin, rats were fed a high-fat diet (19%, w/w) with (HFQ) or without (HF) 0.03% quercetin or a flavonoid-poor low-fat (5%, w/w) maintenance diet (LF) over 4 weeks. Body weight was measured weekly, and plasma concentrations of adiponectin, leptin, insulin, glucose, triacylglycerols, total cholesterol, as well as of markers of inflammation and oxidative stress were measured (12h fasted) at the end of the feeding period. Adiponectin and peroxisome-proliferator-activated-receptor (PPAR)-gamma mRNA were measured in adipose tissue (WAT) by real-time RT-PCR. PPAR-gamma transactivation was investigated by means of a reporter gene assay. HF feeding resulted in elevated fasted plasma glucose concentrations, while HFQ did not differ from LF feeding. In the HFQ group plasma concentrations and WAT mRNA levels of adiponectin were elevated compared with the HF group, however, PPAR-gamma mRNA concentration in WAT was decreased (HFQ vs. HF). Compared to both other groups quercetin feeding significantly reduced oxidative stress, measured by plasma 8-iso-PGF(2alpha), while body weight gain, body composition and plasma leptin levels were not affected. Neither quercetin nor its metabolites induced PPAR-gamma-mediated transactivation in vitro. Adiponectin stimulating effects of quercetin are PPAR gamma-independent and prevent impairment of insulin sensitivity without affecting body weight and composition. PMID- 20580673 TI - Sex steroids effects on the endocrine pancreas. AB - The endocrine pancreas is central in the physiopathology of diabetes mellitus. Nutrients and hormones control endocrine pancreatic function and the secretion of insulin and other pancreatic islet hormones. Although the pancreas is not usually considered as a target of steroids, increasing evidence indicates that sex steroid hormones modify pancreatic islet function. The biological effects of steroid hormones are transduced by both, classical and non-classical steroid receptors that in turn produce slow genomic and rapid non-genomic responses. In this review, we focused on the effects of sex steroid hormones on endocrine pancreatic function, with special emphasis in animal studies. PMID- 20580674 TI - Expression of four mutant fibrinogen gammaC domains in Pichia pastoris confirms them as causes of hypofibrinogenaemia. AB - Mutations in the fibrinogen gene cluster can cause low plasma fibrinogen concentrations, known as hypofibrinogenaemia. It is important to verify whether a detected sequence variant in this cluster is deleterious or benign and this can be accomplished using protein expression systems. In this study, four mutations in the fibrinogen gammaC domain that had previously been described in patients with hypofibrinogenaemia were introduced into a gammaC construct and expressed in a Pichia pastoris yeast system to investigate their effects on protein stability and secretion. These experiments showed that the fibrinogen Middlemore (N230D), Dorfen (A289V), Mannheim II (H307Y), and Muncie (T371I) mutations were not secreted, supporting their causative role in hypofibrinogenaemia. Overexpression of the N230D, A289V and H307Y mutants revealed that the majority of the synthesised protein was retained in the endoplasmic reticulum, with only a minor proportion reaching the trans-Golgi network. Regardless, none of this protein was secreted which confirms that the four mutations investigated are indeed responsible for hypofibrinogenaemia. PMID- 20580675 TI - Production and purification of the penicillin-binding protein 3 from Pseudomonas aeruginosa. AB - The penicillin-binding proteins (PBPs) are peripheral membrane enzymes that catalyze the final steps for the biosynthesis of the essential bacterial cell wall heteropolymer peptidoglycan. Bacteria produce a number and variety of PBPs which are classified as either high molecular weight or low molecular weight PBPs. The high molecular weight PBPs are multimodular being comprised of an N terminal membrane anchor followed by a non-penicillin binding domain and a C terminal penicillin-binding domain. The penicillin-binding domain functions as a serine-acyl transpeptidase to catalyze the crosslinking of neighboring glycan strands within the peptidoglycan sacculus. PBP 3 from Escherichia coli has been studied extensively and it has been shown to be responsible for the synthesis of peptidoglycan during the division and septation of the cells. The opportunistic human pathogen Pseudomonas aeruginosa produces a similar compliment of PBPs to E. coli, but differences in their organization and function have been noted. To investigate these differences further, appropriate quantities of each of the P. aeruginosa PBPs are required in forms amenable for study both in vivo and in vitro. Herein, we describe the cloning and expression of the ftsI gene encoding PBP 3from P. aeruginosa. The PBP was engineered in soluble form to facilitate its study in vitro and with a hexa-His tag to permit its facile purification by affinity chromatography. The recombinant proteins were demonstrated to bind penicillin and these forms of the PBPs were shown to be useful in studying their localization within their host cells by immunogold transmission electron microscopy. PMID- 20580676 TI - Internal lipids of sugarbeet root maggot (Tetanops myopaeformis) larvae: effects of multi-year cold storage. AB - Sugarbeet root maggots, Tetanops myopaeformis (Diptera, Ulidiidae), survive more than five years of laboratory cold (6 degrees C) storage as mature third-instar larvae. To quantify energy costs associated with prolonged storage, internal lipids of larvae stored for 1, 2, 3, and 5 years were compared and characterized with those of field-collected diapausing larvae. Internal lipid concentration was highest (21.8% wet wt. and 29.8% dry wt.) in diapausing larvae. Lipids decreased progressively over storage time with greater than 70% reductions for 5-year stored larvae. Thin-layer chromatographic analysis revealed that triacylglycerols (TAGs) were the most predominant class of internal lipids, with trace amounts of diacylglycerols and hydrocarbons also being present. Gas chromatography-mass spectrometry (GC-MS) analyses of TAG fractions identified ten major fatty acids (FAs). The proportion of unsaturated FAs was higher (73 to 78%) than saturated FAs in diapausing and stored larval groups. Palmitoleic acid (16:1) was the predominant FA, constituting 40-50% of total unsaturated FAs with lesser amounts of myristoleic (14:1), oleic (18:1), lauroleic (12:1), gadoleic (20:1), and the saturated FAs, palmitic (16:0), myristic (14:0), lauric (12:0), stearic (18:0), and arachidic (20:0) being detected at much lower concentrations. Characterization of intact TAGs by high performance liquid chromatography and GC MS revealed the presence of more than 40 TAG constituents. In conclusion, TAGs are utilized as an important energy source for T. myopaeformis larvae during diapause and long-term cold storage with no observed impact of multi-year storage on the TAG composition and distribution of their fatty acids. PMID- 20580677 TI - Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co receptor, CXCR4. AB - Rev, a viral regulatory protein of HIV-1, binds through its arginine-rich domain to the Rev-responsive element (RRE), a secondary structure in transcribed HIV-1 RNA. Binding of Rev to RRE mediates export of singly spliced or unspliced mRNAs from the nucleus to the cytoplasm. It has been previously shown that a certain arginine-rich peptide exhibits not only RRE-binding ability but also cell permeability and antagonism of CXCR4, one of the major coreceptors of HIV-1. Here we designed and synthesized arginine-rich peptides derived from the RNA-binding domain of Rev (Rev(34-50)) and evaluated their anti-HIV-1 activities. Rev(34-50) A(4)C, comprising Rev(34-50) with AAAAC at the C-terminus to increase the alpha helicity, inhibited HIV-1 entry by CXCR4 antagonism and virus production in persistently HIV-1-infected PM1-CCR5 cells. Interestingly, similar motif of human lymphotropic virus type I Rex (Rex(1-21)) also exerted moderate anti-HIV-1 activity. These results indicate that arginine-rich peptide, Rev(34-50)-A(4)C exerts dual antagonism against CXCR4 and Rev. PMID- 20580678 TI - Piceatannol induces Fas and FasL up-regulation in human leukemia U937 cells via Ca2+/p38alpha MAPK-mediated activation of c-Jun and ATF-2 pathways. AB - To verify whether piceatannol-induced death of leukemia cells was associated with Fas-mediated death pathway, the present study was conducted. Piceatannol-induced apoptotic death of human leukemia U937 cells was characterized by increase in intracellular Ca(2+) concentration ([Ca(2+)]i), ERK inactivation, p38 MPAK activation, degradation of procaspase-8 and production of t-Bid. Piceatannol treatment increased Fas and FasL protein expression, and up-regulated transcription of Fas and FasL mRNA. Down-regulation of FADD blocked piceatannol induced procaspase-8 degradation and rescued viability of piceatannol-treated cells. Abolition of piceatannol-induced increase in [Ca(2+)]i abrogated p38 MAPK activation and up-regulation of Fas and FasL expression, but restored ERK activation and viability of piceatannol-treated cells. Suppression of p38alpha MAPK or transfection of constitutively active MEK1 abolished piceatannol-induced Fas and FasL up-regulation. Piceatannol treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38alpha MAPK-mediated c-Jun and ATF-2 phosphorylation. Knockdown of c-Fos, c-Jun and ATF-2 by siRNA reflected that c Fos attenuated the effect of c-Jun and ATF-2 on Fas/FasL up-regulation. Taken together, our data indicate that Fas/FasL up-regulation in piceatannol-treated U937 cells is elicited by Ca(2+)/p38alpha MAPK-mediated activation of c-Jun and ATF-2, and suggest that autocrine Fas-mediated apoptotic mechanism is involved in piceatannol-induced cell death. PMID- 20580679 TI - Histone deacetylase 1 is required for transforming growth factor-beta1-induced epithelial-mesenchymal transition. AB - Epithelial-mesenchymal transition (EMT) has been implicated in embryonic development, fibrosis, and tumor metastasis. Histone deacetylases (HDACs) also play important roles in the control of various physiological and pathological events. However, whether HDACs are involved in the control of EMT in liver cells remains unidentified. Three structurally unrelated HDAC inhibitors completely suppress transforming growth factor-beta1 (TGF-beta1)-induced EMT in AML-12 murine hepatocytes and primary mouse hepatocytes. Expression of a dominant negative mutant of HDAC1 but not HDAC2 or downregulation of HDAC1 but not HDAC2 by RNAi suppressed TGF-beta1-induced EMT. In addition, both HDAC inhibitor TSA and HDAC1 RNAi blocked cell migration. Overexpression of HDAC1 in invasive hepatocellular carcinoma (HCC) samples was detected. Further study showed that the mRNA levels of ZO-1 and E-cadherin were downregulated during TGF-beta1 induced EMT, and HDAC1 can downregulate the promoter activities of ZO-1 and E cadherin. CONCLUSIONS: our results demonstrate that HDAC1 is required for TGF beta1-induced EMT and cell migration in hepatocytes. Its high expression levels in majority of invasive HCC samples suggest that, by promoting EMT, HDAC1 can be related with the invasiveness of HCC. The data also suggest that the repression of transcription of ZO-1 and E-cadherin by HDAC1 may be involved in TGF-beta1 induced EMT. PMID- 20580680 TI - Incidence and etiology of sports-related sudden cardiac death in Denmark- implications for preparticipation screening. AB - BACKGROUND: Studies on incidences of sports-related sudden cardiac death (SrSCD) are few and data are needed for the discussion of preparticipation screening for cardiac disease. OBJECTIVE: We sought to chart the incidence and etiology of SrSCD in the young in Denmark (population 5.4 million) and to compare this to the incidence of sudden cardiac death (SCD) in the background population. METHODS: All 5,662 death certificates for decedents in the period 2000 to 2006 in the age group 12 to 35 years in Denmark were read independently by 2 physicians to identify cases of SCD. Information from autopsy reports, selected hospital records, and multiple registries was used to identify cases of SCD and SrSCD. SrSCD was defined as SCD occurring during or within 1 hour after exercise in a competitive athlete. The size of the athlete population was estimated from national survey data. RESULTS: Fifteen (range 0 to 5 per year) cases of SrSCD were found, 8 of which had antecedent symptoms. The incidence rate was 1.21 (95% confidence interval [CI]: 0.68 to 2.00) per 100,000 athlete person-years. The most common autopsy findings were arrhythmogenic right ventricular cardiomyopathy (n = 4), sudden unexplained death (n = 4), and coronary artery disease (n = 2). The incidence of SCD in the general population age 12 to 35 was 3.76 (95% CI: 3.42 to 4.14) per 100,000 person-years. CONCLUSION: In Denmark, SrSCD is a rare occurrence and the incidence rate is lower than that of SCD in the general population. This may imply a low value of preparticipation screening of athletes in Denmark. PMID- 20580681 TI - Intranasal TRPV1 agonist capsaicin challenge and its effect on c-fos expression in the guinea pig brainstem. AB - Central neuronal interaction seems to play a role in pathogenesis of upper airway cough syndrome. In the guinea pig model we used the method c-fos expression to identify neurons involved in processing of nociceptive nasal stimuli and their contribution to enhancement of cough. 21 spontaneously breathing, urethane anaesthetized animals were used. The controls received intranasal saline, stimulation group received capsaicin (15 microl, 50 microM), and not-treated group was free of nasal challenge. After 2 h animals were deeply anaesthetized, exsanguinated and transcardially perfused with saline and paraformaldehyde. The brainstems were removed, post-fixed, and slices were processed immunohistochemically for c-fos. In capsaicin group the FLI was detected in the nTs 0.5 mm caudal, 1.5 mm lateral to the obex, the area postrema, LRN and VRG. Intensive FLI was identified in trigeminal nuclear complex. Mean number of FOS positive neurons per section was significantly higher in capsaicin group than that in no-treatment controls or saline controls at the level of obex (p<0.01). Neurons of nTs and VRG clearly activated after nasal provocation may participate in enhancement of cough. PMID- 20580682 TI - Experience from use of GMOs in Argentinian agriculture, economy and environment. AB - Argentina is the second largest grower of genetically modified (GM) crops. This high level of adoption of this new agricultural technology is the result of a complex combination of circumstances. We can identify four main causes that led to this: political support (from agriculture officials), ability to solve prevalent farmers' needs, economic and environmental factors and an early implementation of effective regulations. The political willingness to study this new technology and crops as well as the recruitment of sound professionals and scientists to perform the task was crucial. These professionals, with very diverse backgrounds, created the necessary regulatory framework to work with these new crops. Farmers played a decisive role, as adopting this new technology solved some of their agronomic problems, helped them perform more sustainable agronomic practices and provided economic benefits. Nonetheless, all these advancements had not been possible without a rational, science-based and flexible regulatory framework that would make sure that the GM crops were safe for food, feed and processing. PMID- 20580683 TI - Effect of human parathyroid hormone hPTH (1-34) applied at different regimes on fracture healing and muscle in ovariectomized and healthy rats. AB - Three experiments were conducted to investigate the effect of intermittent administration of parathyroid hormone (PTH) (1-34) applied at different regimes on fracture healing and muscle in healthy and ovariectomized (Ovx at 3 months of age) rats. Five-month old rats underwent bilateral transverse metaphyseal osteotomy of tibia and were divided into groups (12 rats each). In Exp 1, Ovx rats were either treated with PTH (7x/w, 1-35d), with oral estradiol-17beta benzoate (0.4 mg/kg BW, 1-35d) or untreated. In Exp. 2, there were 3 groups: healthy untreated or treated with PTH (5x/w, 1-35d or 7-35d). In Exp. 3, there were 7 groups: healthy, Ovx, "healthy PTH 5x/w 7-35d", "Ovx PTH 5x/w 7-35d, 14 35d or 14-28d", "Ovx PTH every other day 7-35d". Single dosage of PTH was 40 microg/kg BW. After 35 days of healing one tibia was analyzed by computed tomographical, biomechanical, histological analyses. The other tibia was used in analyses of Alp, Oc, Trap 1, Igf-1, Rankl, Opg genes (Exp.2, 3). Serum Oc and Alp were measured. Body, uterus weight was recorded. M. gastrocnemius was analyzed for weight (Exp. 2), fiber size and mitochondrial respiratory activity (MRA) (Exp.3). Estrogen enhanced uterus weight, prevented body increase, however, did not improve bone healing in Ovx rats (Exp. 1). PTH administration from days 1 and 7 improved bone parameters in all rats regardless of the application frequency (7, 5x/w or every other day) (Exp. 1, stiffness Ovx: 118+13 N/mm, Ovx PTH: 250+/ 20 N/mm) being more effective in healthy rats (Exp. 3, stiffness improvement Healthy: 59 to 174 N/mm, Ovx: 52 to 98 N/mm). Serum Oc level was elevated in PTH treated rats. Application from day 14 proved to be less effective (Exp. 3). PTH had no effect (P>0.05) on body, uterus and muscle weight, muscle fiber size, MRA and expression of bone markers. PTH promoted bone healing in Ovx and healthy rats, when it is applied during early stage of healing without having any adverse systemic effect. In perspective, PTH may represent a treatment for enhancement of fracture healing. The findings need to be confirmed by follow-up studies on other animals. PMID- 20580684 TI - Parathyroid hormone and bisphosphonate have opposite effects on stress fracture repair. AB - This study was aimed to investigate the effects of Parathyroid hormone (PTH) and alendronate (ALN) on stress fracture repair. Stress fractures were induced in the ulnae of female adult rats. Animals were treated daily with vehicle, PTH (40 microg/kg) or alendronate (2 microg/kg), respectively. Bone mineral content (BMC) and bone mineral density (BMD) of bilateral ulnae were measured at two, four and eight weeks following induction of stress fracture. Histology at the ulna midshaft was undertaken at 2 and 4 weeks and mechanical testing was done at 8 weeks after stress fracture. PTH increased BMC significantly by 7% at 4 weeks and BMD and BMC significantly by 10% and 7% at 8 weeks compared to the control. Alendronate did not change BMD or BMC in comparison with the control. PTH significantly stimulated bone formation by 114% at 2 weeks, increased intracortical resorption area by 23% at 4 weeks, and enhanced the ultimate force of the affected ulnae by 15% at 8 weeks compared to the control. Alendronate significantly suppressed bone formation rate by 44% compared to the control at 4 weeks. These data indicate that PTH may accelerate intracortical bone remodeling induced by microdamage and alendronate may delay intracortical bone remodeling during stress fracture repair in rats. This study suggests that PTH may be used to facilitate stress fracture repair whereas bisphosphonates may delay tissue level repair of stress fractures. PMID- 20580685 TI - Quantification of melittin and apamin in bee venom lyophilized powder from Apis mellifera by liquid chromatography-diode array detector-tandem mass spectrometry. AB - A high-performance liquid chromatography-diode array detector-tandem mass spectrometry (HPLC-DAD-MS/MS) method was developed for simultaneous determination of melittin and apamin in crude bee venom lyophilized powder (CBVLP) as the traditional Chinese medicine possessing specific biological activity. Melittin and apamin were extracted with pure water from CBVLP samples followed by HPLC-DAD MS/MS analysis. The method was validated to demonstrate its selectivity, linearity, limit of quantification (LOQ), intraday precision, interday precision, accuracy, recovery, matrix effect, and stability. The assay was linear over the concentration ranges of 1-100 and 0.2-25 microg/ml with limit of quantifications (LOQs) of 1.0 and 0.3 microg/ml for melittin and apamin, respectively. The precision results were expressed as coefficients of variation (CVs), ranging from 2.2% to 11.4% for intraday repeatability and from 3.2% to 13.1% for interday intermediary precision. The concentrations of endogenous melittin and apamin in CBVLP samples ranged from 46% to 53% and from 2.2% to 3.7% of dry weight, respectively. This rapid, simple, precise, and sensitive method allowed the simultaneous determination of melittin and apamin to evaluate authenticity and quality of CBVLP samples. PMID- 20580686 TI - Urokinase receptor (uPAR) regulates complement receptor 3 (CR3)-mediated neutrophil phagocytosis. AB - Urokinase receptor (uPAR) associates in cis with complement receptor 3 (CR3). In the present study, we addressed whether this coupling regulates CR3-mediated phagocytosis. CR3-mediated attachment of iC3b-opsonized sheep red blood cells to human neutrophils and internalization of these cells were reduced by removal of cell-bound uPAR by phosphatidylinositol-specific phospholipase C and reconstituted in the presence of soluble uPAR. The attachment and internalization were suppressed in the presence of anti-uPAR polyclonal antibody, proteolytically inactive urokinase and saccharides that disrupt interaction of uPAR with CR3. Thus, uPAR acts as a cofactor for iC3b binding to CR3 and regulates CR3-mediated phagocytosis. PMID- 20580687 TI - Single intravenous injection of plasmid DNA encoding human paraoxonase-1 inhibits hyperlipidemia in rats. AB - Paraoxonase-1 (PON1, EC 3.1.8.1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme, and its activity correlates negatively with the level of plasma low-density lipoprotein cholesterol (LDL-C) and triglyceridemia (TG). In this study, we examined the therapeutic effect of plasmid DNA containing the human PON1 gene (pcDNA/PON1) in hyperlipidemic model rats. The rats were fed a high-fat and high-cholesterol diet for 25 days to produce a hyperlipidemic animal model. Single intravenous injection of pcDNA/PON1 into model rats prevented dyslipidemia and hepatic lipid accumulation. The mechanisms of pcDNA/PON1 in treating hyperlipidemia were associated with increases of serum antioxidant PON1 and SOD activities, and with reduction of the levels of total cholesterol (TC), LDL-C and TG. The results suggest the potential therapeutic effect of pcDNA/PON1 on hyperlipidemia. PMID- 20580688 TI - Mechanical stress-evoked but angiotensin II-independent activation of angiotensin II type 1 receptor induces cardiac hypertrophy through calcineurin pathway. AB - Mechanical stress can induce cardiac hypertrophy through angiotensin II (AngII) type 1 (AT(1)) receptor independently of AngII, however, the intracellular mechanisms remain largely indeterminate. Since calcineurin, a Ca(2+)-dependent phosphatase, plays a critical role in pressure overload-induced cardiac hypertrophy, we therefore, asked whether calcineurin is involved in the AT(1) receptor-mediated but AngII-independent cardiac hypertrophy. Mechanical stretch failed to elicit hypertrophic responses in COS7 cells co-transfected with plasmid of AT(1) receptor and siRNA of calcineurin. Mechanical stresses for 2weeks in vivo and for 24h in vitro significantly induced upregulation of calcineurin expression and hypertrophic responses, such as the increases in cardiomyocytes size and specific gene expressions, in cardiomyocytes of angiotensinogen gene knockout (ATG(-/-)) mice, both of which were significantly suppressed by a specific calcineurin inhibitor FK506, suggesting a critical role of calcineurin in mechanical stress-induced cardiac hypertrophy in the ATG(-/-) mice. Furthermore, an AT(1) receptor blocker Losartan not only attenuated cardiac hypertrophy but also abrogated upregulation of cardiac calcineurin expression induced by mechanical stresses in the AngII-lacking mice, indicating that calcineurin expression is regulated by AT(1) receptor without the involvement of AngII after mechanical stress. These findings collectively suggest that mechanical stress-evoked but AngII-independent activation of AT(1) receptor induces cardiac hypertrophy through calcineurin pathway. PMID- 20580689 TI - Human erythrocytes and neuroblastoma cells are affected in vitro by Au(III) ions. AB - Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl(3) was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 microM; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 microM concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 microm-1mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 microM to 100 microM. PMID- 20580690 TI - Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway. AB - Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently, H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP 1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLCbeta2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLCbeta2/Ca2+ signal transduction in endothelial cells. PMID- 20580691 TI - Mitofusin-2 protects against cold stress-induced cell injury in HEK293 cells. AB - Mitochondrial impairment is hypothesized to contribute to cell injury during cold stress. Mitochondria fission and fusion are closely related in the function of the mitochondria, but the precise mechanisms whereby these processes regulate cell injury during cold stress remain to be determined. HEK293 cells were cultured in a cold environment (4.0+/-0.1 degrees C) for 2, 4, 8, or 12h. Western blot analyses showed that these cells expressed decreased fission-related protein Drp1 and increased fusion-related protein Mfn2 at 4h; meanwhile, electron microscopy analysis revealed large and long mitochondrial morphology within these cells, indicating increased mitochondrial fusion. With silencing of Mfn2 but not of Mfn1 by siRNA promoted cold-stress-induced cell death with decreased ATP production in HEK293 cells. Our results show that increased expression of Mfn2 and mitochondrial fusion are important for mitochondrial function as well as cell survival during cold stress. These findings have important implications for understanding the mechanisms of mitochondrial fusion and fission in cold-stress induced cell injury. PMID- 20580692 TI - Central and peripheral components of writing critically depend on a defined area of the dominant superior parietal gyrus. AB - Classical neuropsychological models of writing separate central (linguistic) processes common to oral spelling, writing and typing from peripheral (motor) processes that are modality specific. Damage to the left superior parietal gyrus, an area of the cortex involved in peripheral processes specific to handwriting, should generate distorted graphemes but not misspelled words, while damage to other areas of the cortex like the frontal lobe should produce alterations in written and oral spelling without distorted graphemes. We describe the clinical and neuropsychological features of a patient with combined agraphia for handwriting and typewriting bearing a small glioblastoma in the left parietal lobe. His agraphia resolved after antiedema therapy and we tested by bipolar cortical stimulation his handwriting abilities during an awake neurosurgical procedure. We found that we could reversibly re-induce the same defects of writing by stimulating during surgery a limited area of the superior parietal gyrus in the same patient and in an independent patient that was never agraphic before the operation. In those patients stimulation caused spelling errors, poorly formed letters and in some cases a complete cessation of writing with minimal or no effects on oral spelling. Our results suggest that stimulating a specific area in the superior parietal gyrus we can generate different patterns of agraphia. Moreover, our findings also suggest that some of the central processes specific for typing and handwriting converge with motor processes at least in the limited portion of the superior parietal gyrus we mapped in our patients. PMID- 20580693 TI - Depolarizing shift in the GABA-induced current reversal potential by lidocaine hydrochloride. AB - Lidocaine hydrochloride (LC-HCl) is widely used as a local anesthetic, while various adverse effects of LC-HCl, such as seizures have also been reported. Lidocaine is reported to inhibit various channels and receptors including GABA(A) receptors. Although the GABA(A) receptor-mediated response depends on Cl(-) equilibrium potential (E(Cl)), little is known about the effect of LC-HCl on E(Cl). In the present study, we investigated the effect of LC-HCl on GABA-induced currents in cultured rat hippocampal neurons with gramicidin-perforated patch clamp recording which is known to keep the intracellular Cl(-) concentration intact. LC-HCl inhibited outward GABA-induced currents with depolarizing shift of the GABA reversal potential (E(GABA)). The LC-HCl-induced positive E(GABA) shift was not observed with conventional whole-cell patch-clamp method which cannot retain intact intracellular Cl(-) concentration. The LC-HCl action on E(GABA) was inhibited by either furosemide, a blocker of both Na(+)-K(+)-Cl(-) cotransporter (NKCC) and K(+)-Cl(-) cotransporter (KCC), or an increase in extracellular K(+) concentrations. Neither bumetanide, a specific inhibitor of NKCC, nor Na(+)-free external solution had any effect on the LC-HCl-induced E(GABA) shift. QX-314, a membrane impermeable lidocaine derivative, failed to shift E(GABA) to positive potential. Furthermore, LC-HCl caused a depolarizing shift of E(GABA) in cultured GT1-7 cells expressing KCC2 but failed to change E(GABA) in GT1-7 cells without expression of KCC2. These results suggest that the LC-HCl-induced positive E(GABA) shift is due to a blockade of KCC2. Together with the direct LC-HCl action to GABA(A) receptors, the positive E(GABA) shift induced by LC-HCl reduces the GABAergic inhibition in the central nervous system. PMID- 20580694 TI - To switch or not to switch: brain potential indices of attentional control after task-relevant and task-irrelevant changes of stimulus features. AB - Attention is controlled by the interplay of sensory input and top-down processes. We compared attentional control processes during task switching and reorientation after distraction. The primary task was to discriminate laterally and centrally presented tones; these stimuli were composed of a frequent standard or an infrequent deviant pitch. In the distraction condition, pitch was irrelevant and could be ignored. In the switch condition, pitch changes were relevant: whenever a deviant tone was presented, participants had to discriminate its pitch and not its direction. The task in standard trials remained unchanged. In both conditions, deviants elicited mismatch negativity (MMN), P3a, P3b, and reorienting negativity (RON). We, therefore, suggest that distraction and switching are triggered by the same system of attentional control. In addition, remarkable differences were observable between the two conditions: In the switch condition the MMN was followed by a more pronounced N2b and P3a. The differences between these components support the idea that in the distraction condition, a switch of attention is only initiated but not completely performed. PMID- 20580695 TI - In vitro transcription of compound heterozygous hypofibrinogenemia Matsumoto IX; first identification of FGB IVS6 deletion of 4 nucleotides and FGG IVS3-2A>G causing abnormal RNA splicing. AB - BACKGROUND: We reported a case of hypofibrinogenemia Matsumoto IX (M IX) caused by a novel compound heterozygous mutation involving an FGB IVS6 deletion of 4 nucleotides (Delta4b) (three T, one G; between FGB IVS6-10 and -16) and FGG IVS3 2A/G, which are both identified for the first time. To examine the transcription of mRNA from the M IX gene, we cloned the wild-type and mutant genes into expression vectors. METHODS: The vectors were transfected into CHO cells and transiently produced wild-type, Bbeta- or gamma-mRNA in the cells. The mRNAs amplified with RT-PCR were analyzed by agarose gel electrophoresis and nucleotide sequencing. RESULTS: The RT-PCR product from FGB IVS6Delta4b showed aberrant mRNA that included both introns 6 and 7, and that from FGG IVS3-2G showed two aberrant mRNAs, a major one including intron 3 and a minor in which intron 3 was spliced by a cryptic splice site in exon 4. We speculated that the aberrant mRNAs are degraded before translation into proteins, and/or translated variant chains are subjected to quality control and degraded in the cytoplasm. CONCLUSION: The reduced plasma fibrinogen level of the M IX patient was caused by abnormal RNA splicing of one or both of the FGB and FGG genes. PMID- 20580696 TI - Relevance of copper and ceruloplasmin in psoriasis. PMID- 20580697 TI - Differences in serum creatinine concentration between Caucasians, Chinese, Indians and Malays. PMID- 20580698 TI - Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects. AB - BACKGROUND: Several studies have reported that serum concentrations of carotenoids and adiponectin are inversely associated with the risk for cardiovascular disease (CVD). However, no studies have investigated the association between serum concentrations of adiponectin and carotenoids in the general population. METHODS: We investigated cross-sectionally whether serum carotenoids are associated with serum high molecular weight (HMW) adiponectin and some inflammatory markers in 437 Japanese subjects (116 men and 321 women) who attended a health examination. RESULTS: In multiple linear regression analysis adjusted for confounding factors, serum beta-carotene concentrations were significantly associated with serum HMW adiponectin concentrations in both sexes (standardized beta coefficient=0.197, p=0.036 for men; standardized beta coefficient=0.146, p=0.012 for women). Serum alpha-carotene and beta-carotene concentrations were significantly associated with serum C-reactive protein (CRP) concentrations in men. In women, there were significant negative associations between serum carotenoids concentrations and serum interleukin-6 (IL-6) concentrations. Additional adjustment for serum concentrations of IL-6 or CRP did not significantly affect the association between carotenoids and HMW adiponectin in non-smoking men as well as in women. CONCLUSION: Serum beta-carotene concentrations were positively associated with serum HMW adiponectin concentrations even after adjustment for possible confounding factors including inflammatory markers. PMID- 20580699 TI - Soluble P selectin in synovial fluid level is correlated with the radiographic severity of knee osteoarthritis. AB - BACKGROUND: Recent studies provide evidence that inflammation is a feature of the disease process in Osteoarthritis (OA). The clinical significance of P selectin (Ps) in OA has not been adequately studied and the association between Ps level and OA severity remains unknown. METHODS: We enrolled 120 knee OA subjects and 45 controls. All patients were scored for Kellgren-Lawrence grade (0-4). The Ps in serum and synovial fluid (SF) as well as serum C-reactive protein (CRP) levels were detected. RESULTS: The mean Ps level in OA subjects was markedly increased than that in controls. In OA patients, the SF Ps levels increased with the severity of KL scores and significantly correlated with severity of disease (r=0.546, P<0.001) and serum CRP level (r=0.488, P<0.001). However, the serum Ps level did not show a significant correlation with the severity of OA. CONCLUSION: The Ps levels in SF were significantly correlated with the severity of OA, suggesting that it may be used as a biomarker to evaluate the progression of OA. PMID- 20580700 TI - Genetic interactions of eyes absent, twin of eyeless and orthodenticle regulate sine oculis expression during ocellar development in Drosophila. AB - The homeobox gene sine oculis (so) is required for the development of the entire visual system in Drosophila, which includes the compound eyes, the ocelli, the optic lobe of the brain and the Bolwig's organ. During ocelli development, so expression labels, together with eyes absent (eya), the emergence of the ocellar precursor cells in the third instar eye-antennal disc. Footprinting and misexpression studies have led to the proposal that the Pax6 homologue twin of eyeless (toy) directly regulates the initiation of so expression in ocellar precursor cells. However, so expression in a toy loss-of-function mutant background has not been yet analyzed due to the lack of eye-antennal disc development in strong toy mutant alleles. Using an embryonic eye primordium specific enhancer of toy, we have rescued the developmental defect of a strong toy mutant allele and analyzed so expression in the ocelli primordium of toy loss of-function eye-antennal discs during third instar larva. The results show that so expression is only marginally affected in the absence of Toy transcriptional activity and that the toy positive effect on so expression is largely eya mediated. These results suggest that eya is the main factor controlling both initiation and maintenance of so expression in ocellar precursor cells. In addition, we present the characterization of a new minimal eye/ocellus-specific enhancer of the so gene. PMID- 20580701 TI - Regulation of the sperm EGF receptor by ouabain leads to initiation of the acrosome reaction. AB - The sperm acrosome reaction occurs after the binding of the capacitated sperm to the egg zona pellucida. This study describes a novel mode of regulation of the sperm epidermal growth factor receptor (EGFR) under physiological conditions and its relevance to the acrosome reaction. Ouabain, a known Na/K ATPase blocker is present in the blood and in the female reproductive tract. We show here that physiological concentrations (nM) of ouabain enhance phosphorylation of EGFR on tyr-845, stimulate Ca(2+) influx and induce the acrosome reaction in sperm. These effects could be seen only in the presence of very low concentrations of EGF (0.1 ng/ml or 0.016 nM) added together with nano-molar ouabain. Phosphorylation, Ca(2+) influx, and the acrosome reaction are inhibited by an EGFR blocker, suggesting that trans-activation of the EGFR is involved. Moreover, our data revealed that protein kinase A and the family of tyrosine kinase, SRC, shown before to be involved in EGFR activation in sperm, mediate the acrosome reaction induced by ouabain. Ouabain alone (without EGF) at relatively high concentration (10microM) could enhance EGFR phosphorylation, Ca(2+) influx and acrosome reaction, and these processes were inhibited by EGFR blockers. Moreover, we show here that PKA and SRC family are involved in the activation of EGFR by 10 microM ouabain, further demonstrating that ouabain induces the acrosome reaction by a mechanism mediated by the trans-activation of EGFR. In conclusion, this study describes an interesting regulatory path of EGFR by physiological concentrations of ouabain and EGF found in the female reproductive tract. Neither of these compounds can activate the EGFR alone at such low physiological levels; however, when both are present, the interaction of ouabain with the Na/K ATPase leads to the priming of the EGFR, which undergoes its full activation by EGF. PMID- 20580702 TI - Stabilization of ATF4 protein is required for the regulation of epithelial mesenchymal transition of the avian neural crest. AB - Epithelial-mesenchymal transition (EMT) permits neural crest cells to delaminate from the epithelial ectoderm and to migrate extensively in the embryonic environment. In this study, we have identified ATF4, a basic-leucine-zipper transcription factor, as one of the neural crest EMT regulators. Although ATF4 alone was not sufficient to drive the formation of migratory neural crest cells, ATF4 cooperated with Sox9 to induce neural crest EMT by controlling the expression of cell-cell and cell-extracellular matrix adhesion molecules. This was likely, at least in part, by inducing the expression of Foxd3, which encodes another neural crest transcription factor. We also found that the ATF4 protein level was strictly regulated by proteasomal degradation and p300-mediated stabilization, allowing ATF4 protein to accumulate in the nuclei of neural crest cells undergoing EMT. Thus, our results emphasize the importance of the regulation of protein stability in the neural crest EMT. PMID- 20580704 TI - The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. AB - Unlike normal cells, tumor cells survive in a specific redox environment where the elevated reactive oxygen species contribute to enhance cell proliferation and to suppress apoptosis. Alpha-lipoic acid, a naturally occurring reactive oxygen species scavenger, has been shown to possess anticancer activity, due to its ability to suppress proliferation and to induce apoptosis in different cancer cell lines. Since at the moment little information is available regarding the potential effects of alpha-lipoic acid on breast cancer, in the present study we addressed the question whether alpha-lipoic acid induces cell cycle arrest and apoptosis in the human breast cancer cell line MCF-7. Moreover, we investigated some molecular mechanisms which mediate alpha-lipoic acid actions, focusing on the role of the PI3-K/Akt signalling pathway. We observed that alpha-lipoic acid is able to scavenge reactive oxygen species in MCF-7 cells and that the reduction of reactive oxygen species is followed by cell growth arrest in the G1 phase of the cell cycle, via the specific inhibition of Akt pathway and the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1), and by apoptosis, via changes of the ratio of the apoptotic-related protein Bax/Bcl-2. Thus, the anti-tumor activity of alpha-lipoic acid observed in MCF-7 cells further stresses the role of redox state in regulating cancer initiation and progression. PMID- 20580703 TI - A compartmental model for the bicoid gradient. AB - The anterior region of the Drosophila embryo is patterned by the concentration gradient of the homeodomain transcription factor bicoid (Bcd). The Bcd gradient was the first identified morphogen gradient and continues to be a subject of intense research at multiple levels, from the mechanisms of RNA localization in the oocyte to the evolution of the Bcd-mediated patterning events in multiple Drosophila species. Critical assessment of the mechanisms of the Bcd gradient formation requires biophysical models of the syncytial embryo. Most of the proposed models rely on reaction-diffusion equations, but their formulation and applicability at high nuclear densities is a nontrivial task. We propose a straightforward alternative in which the syncytial blastoderm is approximated by a periodic arrangement of well-mixed compartments: a single nucleus and an associated cytoplasmic region. We formulate a compartmental model, constrain its parameters by experimental data, and demonstrate that it provides an adequate description of the Bcd gradient dynamics. PMID- 20580705 TI - Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways. AB - The herbal products baicalin, baicalein, chlorogenic acid, and ginsenoside Rf have multiple pharmacological effects and are extensively used in alternative and/or complementary therapies. The present study investigated whether baicalin, baicalein, chlorogenic acid, and ginsenoside Rf induced the expression of the cytochrome P450 3A4 (CYP3A4) and multi-drug resistance 1 (MDR1) genes through the pregnane X receptor and constitutive androstane receptor pathways. Real time PCR, western blotting, and a luminescent assay were used to assess the induction of gene expression and activity of CYP3A4 and MDR1 by the test compounds. The interactions of baicalein/chlorogenic acid/ginsenoside Rf with constitutive androstane receptor and pregnane X receptor were evaluated using luciferase reporter and gel shift assays. Baicalein induced the expression of CYP3A4 and MDR1 mRNA by activating pregnane X receptor and constitutive androstane receptor. Chlorogenic acid and ginsenoside Rf showed a relatively weak effect on CYP3A4 promoter activation only in HepG2 cells cotransfected with constitutive androstane receptor and demonstrated no effects on MDR1 via either the constitutive androstane receptor or pregnane X receptor pathway. Baicalin had no effect on either CYP3A4 or MDR1 gene expression. In conclusion, baicalein has the potential to up-regulate CYP3A4 and MDR1 through the direct activation of the constitutive androstane receptor and pregnane X receptor pathways. Chlorogenic acid and ginsenoside Rf only induced constitutive androstane receptor-mediated CYP3A4 expression. PMID- 20580706 TI - Myoblast fusion in Drosophila. AB - The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral side of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process [1 4]. With apologies, we use gene nomenclature as specified by Flybase (http://flybase.org) but provide Table 1 with alternative names and references. PMID- 20580708 TI - Phosphorylation statuses at different residues of lamin B2, B1, and A/C dynamically and independently change throughout the cell cycle. AB - Lamins, major components of the nuclear lamina, undergo phosphorylation at multiple residues during cell cycle progression, but their detailed phosphorylation kinetics remain largely undetermined. Here, we examined changes in the phosphorylation of major phosphorylation residues (Thr14, Ser17, Ser385, Ser387, and Ser401) of lamin B2 and the homologous residues of lamin B1, A/C during the cell cycle using novel antibodies to the site-specific phosphorylation. The phosphorylation levels of these residues independently changed during the cell cycle. Thr14 and Ser17 were phosphorylated during G(2)/M phase to anaphase/telophase. Ser385 was persistently phosphorylated during mitosis to G(1) phase, whereas Ser387 was phosphorylated discontinuously in prophase and G(1) phase. Ser401 phosphorylation was enhanced in the G(1)/S boundary. Immunoprecipitation using the phospho-antibodies suggested that metaphase-phosphorylation at Thr14, Ser17, and Ser385 of lamins occurred simultaneously, whereas G(1)-phase phosphorylation at Ser385 and Ser387 occurred in distinct pools or with different timings. Additionally, we showed that lamin B2 phosphorylated at Ser17, but not Ser385, Ser387 and Ser401, was exclusively non-ionic detergent soluble, depolymerized forms in growing cells, implicating specific involvement of Ser17 phosphorylation in lamin depolymerization and nuclear envelope breakdown. These results suggest that the phosphorylations at different residues of lamins might play specific roles throughout the cell cycle. PMID- 20580707 TI - Syndecan-1 regulates cell migration and fibronectin fibril assembly. AB - Corneal scarring is a major cause of blindness worldwide and can result from the deposition of abnormal amounts of collagen fibers lacking the correct size and spacing required to produce a clear cornea. Collagen fiber formation requires a preformed fibronectin (FN) matrix. We demonstrate that the loss of syndecan1 (sdc1) in corneal stromal cells (CSC) impacts cell migration rates, the sizes and composition of focal and fibrillar adhesions, the activation of integrins, and the assembly of fibronectin into fibrils. Integrin and fibronectin expression are not altered on sdc1-null CSCs. Cell adhesion, spreading, and migration studies using low compared to high concentrations of FN and collagen I (CNI) or vitronectin (VN) with and without activation of integrins by manganese chloride show that the impact of sdc1 depletion on integrin activation varies depending on the integrin-mediated activity evaluated. Differences in FN fibrillogenesis and migration in sdc1-null CSCs are reversed by addition of manganese chloride but cell spreading differences remain. To determine if our findings on sdc1 were specific to the cornea, we compared the phenotypes of sdc1-null dermal fibroblasts with those of CSCs. We found that without sdc1, both cell types migrate faster; however, cell-type-specific differences in FN expression and its assembly into fibrils exist between these two cell types. Together, our data demonstrate that sdc1 functions to regulate integrin activity in multiple cell types. Loss of sdc1-mediated integrin function results in cell-type specific differences in matrix assembly. A better understanding of how different cell types regulate FN fibril formation via syndecans and integrins will lead to better treatments for scarring and fibrosis. PMID- 20580709 TI - Gene therapy for muscle disease. AB - The molecular mechanisms of Duchenne muscular dystrophy (DMD) have been extensively investigated since the discovery of the dystrophin gene in 1986. Nonetheless, there is currently no effective treatment for DMD. Recent reports, however, indicate that adenoassociated viral (AAV) vector-mediated transfer of a functional dystrophin cDNA into the affected muscle is a promising strategy. In addition, antisense-mediated exon skipping technology has been emerging as another promising approach to restore dystrophin expression in DMD muscle. Ongoing clinical trials show restoration of dystrophin in DMD patients without serious side effects. Here, we summarize the recent progress in gene therapy, with an emphasis on exon skipping for DMD. PMID- 20580710 TI - Skeletal muscle: energy metabolism, fiber types, fatigue and adaptability. AB - Skeletal muscles cope with a large range of activities, from being able to support the body weight during long periods of upright standing to perform explosive movements in response to an unexpected threat. This requires systems for energy metabolism that can provide energy during long periods of moderately increased energy consumption as well as being able to rapidly increasing the rate of energy production more than 100-fold in response to explosive contractions. In this short review we discuss how muscles can deal with these divergent demands. We first outline the major energy metabolism pathways in skeletal muscle. Next we describe metabolic differences between different muscle fiber types. Contractile performance declines during intense activation, i.e. fatigue develops, and we discuss likely underlying mechanisms. Finally, we discuss the ability of muscle fibers to adapt to altered demands, and mechanisms behind these adaptations. The accumulated experimental evidence forces us to conclude that most aspects of energy metabolism involve multiple and overlapping signaling pathways, which indicates that the control of energy metabolism is too important to depend on one single molecule or mechanism. PMID- 20580711 TI - Transcription factor KLF7 regulates differentiation of neuroectodermal and mesodermal cell lineages. AB - Previous gene targeting studies in mice have implicated the nuclear protein Kruppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required for in vitro differentiation of neuroectodermal and mesodermal cells. Specifically, we show a correlation of Klf7 silencing with down-regulation of the neuronal marker microtubule-associated protein 2 (Map2) and the nerve growth factor (NGF) tyrosine kinase receptor A (TrkA) using the PC12 neuronal cell line. Similarly, KLF7 inactivation in Klf7 null mice decreases the expression of the neurogenic marker brain lipid-binding protein/fatty acid-binding protein 7 (BLBP/FABP7) in neural stem cells (NSCs). We also report that Klf7 silencing is detrimental to neuronal and cardiomyocytic differentiation of embryonic stem cells (ESCs), in addition to altering the adipogenic and osteogenic potential of mouse embryonic fibroblasts (MEFs). Finally, our results suggest that genes that are key for self-renewal of undifferentiated ESCs repress Klf7 expression in ESCs. Together with previous findings, these results provide evidence that KLF7 has a broad spectrum of regulatory functions, which reflect the discrete cellular and molecular contexts in which this transcription factor operates. PMID- 20580712 TI - Estrogen and angiotensin interaction in the substantia nigra. Relevance to postmenopausal Parkinson's disease. AB - Epidemiological studies have reported that the incidence of Parkinson's disease (PD) is higher in postmenopausal than in premenopausal women of similar age. Several laboratory observations have revealed that estrogen has protective effects against dopaminergic toxins. The mechanism by which estrogen protects dopaminergic neurons has not been clarified, although estrogen-induced attenuation of the neuroinflammatory response plays a major role. We have recently shown that activation of the nigral renin-angiotensin system (RAS), via type 1 (AT1) receptors, leads to NADPH complex and microglial activation and induces dopaminergic neuron death. In the present study we investigated the effect of ovariectomy and estrogen replacement on the nigral RAS and on dopaminergic degeneration induced by intrastriatal injection of 6-OHDA. We observed a marked loss of dopaminergic neurons in ovariectomized rats treated with 6-OHDA, which was significantly reduced by estrogen replacement or treatment with the AT1 receptor antagonist candesartan. We also observed that estrogen replacement induces significant downregulation of the activity of the angiotensin converting enzyme as well as downregulation of AT1 receptors, upregulation of AT2 receptors and downregulation of the NADPH complex activity in the substantia nigra in comparison with ovariectomized rats. The present results suggest that estrogen-induced down-regulation of RAS and NADPH activity may be associated with the reduced risk of PD in premenopausal women, and increased risk in conditions causing early reduction in endogenous estrogen, and that manipulation of brain RAS system may be an efficient approach for the prevention or coadjutant treatment of PD in estrogen-deficient women. PMID- 20580713 TI - Voluntary ankle flexor activity and adaptive coactivation gain is decreased by spasticity during subacute spinal cord injury. AB - Although spasticity has been defined as an increase in velocity-dependent stretch reflexes and muscle hypertonia during passive movement, the measurement of flexor muscle paresis may better characterize the negative impact of this syndrome on residual motor function following incomplete spinal cord injury (iSCI). In this longitudinal study Tibialis Anterior (TA) muscle paresis produced by a loss in maximal voluntary contraction during dorsiflexion and ankle flexor muscle coactivation during ramp-and-hold controlled plantarflexion was measured in ten patients during subacute iSCI. Tibialis Anterior activity was measured at approximately two-week intervals between 3-5 months following iSCI in subjects with or without spasticity, characterized by lower-limb muscle hypertonia and/or involuntary spasms. Following iSCI, maximal voluntary contraction ankle flexor activity was lower than that recorded from healthy subjects, and was further attenuated by the presence of spasticity. Furthermore the initially high percentage value of TA coactivation increased at 75% but not at 25% maximal voluntary torque (MVT), reflected by an increase in TA coactivation gain (75%/25% MVT) from 2.5+/-0.4 to 7.5+/-1.9, well above the control level of 2.9+/-0.2. In contrast contraction-dependent TA coactivation gain decreased from 2.4+/-0.3 to 1.4+/-0.1 during spasticity. In conclusion the adaptive increase in TA coactivation gain observed in this pilot study during subacute iSCI was also sensitive to the presence of spasticity. The successful early diagnosis and treatment of spasticity would be expected to further preserve and promote adaptive motor function during subacute iSCI neurorehabilitation. PMID- 20580714 TI - Norspermine substitutes for thermospermine in the control of stem elongation in Arabidopsis thaliana. AB - Thermospermine is a structural isomer of spermine and is required for stem elongation in Arabidopsis thaliana. We noted the C3C3 arrangement of carbon chains in thermospermine (C3C3C4), which is not present in spermine (C3C4C3), and examined if it is functionally replaced with norspermine (C3C3C3) or not. Exogenous application of norspermine to acl5, a mutant defective in the synthesis of thermospermine, partially suppressed its dwarf phenotype, and down-regulated the level of the acl5 transcript which is much higher than that of the ACL5 transcript in the wild type. Furthermore, in the Zinnia culture, differentiation of mesophyll cells into tracheary elements was blocked by thermospermine and norspermine but not by spermine. Our results indicate that norspermine can functionally substitute for thermospermine. PMID- 20580715 TI - REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1. AB - The ubiquitin ligase Smad ubiquitination regulatory factor 1 (Smurf1) targets many proteins including Smad1/5 for ubiquitin-dependent proteasomal degradation. However, how Smurf1 is degraded remains unclear. Here we show that REGgamma, an activator for the 20S proteasome-mediated protein degradation, interacts with Smurf1 and mediates its degradation. We provide evidence that depletion of REGgamma stabilizes Smurf1 whereas overexpression of REGgamma promotes the degradation of Smurf1. Interestingly both Smurf2 and Smurf1 are destabilized by the REGgamma proteasome while the other members of Neural precursor cell expressed developmentally downregulated gene 4 family were not affected. More importantly, we found that the REGgamma proteasome-mediated degradation of Smurf1 results in degradation of Smad5. These findings reveal that the REGgamma proteasome targets a ubiquitin ligase for protein degradation. PMID- 20580716 TI - Regulation of homologous recombination at telomeres in budding yeast. AB - Homologous recombination is suppressed at normal length telomere sequences. In contrast, telomere recombination is allowed when telomeres erode in the absence of telomerase activity or as a consequence of nucleolytic degradation or incomplete replication. Here, we review the mechanisms that contribute to regulating mitotic homologous recombination at telomeres and the role of these mechanisms in signalling short telomeres in the budding yeast Saccharomyces cerevisiae. PMID- 20580717 TI - Loss of a DNA binding site within the tail of prelamin A contributes to altered heterochromatin anchorage by progerin. AB - Mutations in the lamin A/C (LMNA) gene that cause Hutchinson-Gilford progeria syndrome (HGPS) lead to expression of a protein called progerin with 50 amino acids deleted from the tail of prelamin A. In cells from patients with HGPS, both the amount and distribution of heterochromatin are altered. We designed in vitro assays to ask whether such alterations might reflect changes in chromatin, DNA and/or histone binding properties of progerin compared to wild-type lamin C terminal tails. We show that progerin tail has a reduced DNA/chromatin binding capacity and modified trimethylated H3K27 binding pattern, offering a molecular mechanism for heterochromatin alterations related to HGPS. PMID- 20580718 TI - Multiple roles of ATM in monitoring and maintaining DNA integrity. AB - The ability of our cells to maintain genomic integrity is fundamental for protection from cancer development. Central to this process is the ability of cells to recognize and repair DNA damage and progress through the cell cycle in a regulated and orderly manner. In addition, protection of chromosome ends through the proper assembly of telomeres prevents loss of genetic information and aberrant chromosome fusions. Cells derived from patients with ataxia telangiectasia (A-T) show defects in cell cycle regulation, abnormal responses to DNA breakage, and chromosomal end-to-end fusions. The identification and characterization of the ATM (ataxia-telangiectasia, mutated) gene product has provided an essential tool for researchers in elucidating cellular mechanisms involved in cell cycle control, DNA repair, and chromosomal stability. PMID- 20580719 TI - A bacterial ortholog of class II lysyl-tRNA synthetase activates lysine. AB - Aminoacyl-tRNA synthetases produce aminoacyl-tRNAs, essential substrates for accurate protein synthesis. Beyond their central role in translation some of these enzymes or their orthologs are recruited for alternative functions, not always related to their primary cellular role. We investigate here the enzymatic properties of GenX (also called PoxA and YjeA), an ortholog of bacterial class II lysyl-tRNA synthetase. GenX is present in most Gram-negative bacteria and is homologous to the catalytic core of lysyl-tRNA synthetase, but it lacks the amino terminal anticodon binding domain of the latter enzyme. We show that, in agreement with its well-conserved lysine binding site, GenX can activate in vitro l-lysine and lysine analogs, but does not acylate tRNA(Lys) or other cellular RNAs. PMID- 20580720 TI - Phosphoinositide 3-kinase signaling mediates beta-catenin activation in intestinal epithelial stem and progenitor cells in colitis. AB - BACKGROUND & AIMS: Mechanisms responsible for crypt architectural distortion in chronic ulcerative colitis (CUC) are not well understood. Data indicate that serine/threonine protein kinase Akt (Akt) signaling cooperates with Wingless (Wnt) to activate beta-catenin in intestinal stem and progenitor cells through phosphorylation at Ser552 (P-beta-catenin(552)). We investigated whether phosphoinositide 3-kinase (PI3K) is required for Akt-mediated activation of beta catenin during intestinal inflammation. METHODS: The class IA subunit of PI3K was conditionally deleted from intestinal epithelial cells in mice named I-pik3r1KO. Acute inflammation was induced in mice and intestines were analyzed by biochemical and histologic methods. The effects of chemically blocking PI3K in colitic interleukin-10(-/-) mice were examined. Biopsy samples from patients were examined. RESULTS: Compared with wild-type, I-pik3r1KO mice had reduced T-cell mediated Akt and beta-catenin signaling in intestinal stem and progenitor cells and limited crypt epithelial proliferation. Biochemical analyses indicated that PI3K-Akt signaling increased nuclear total beta-catenin and P-beta-catenin(552) levels and reduced N-terminal beta-catenin phosphorylation, which is associated with degradation. PI3K inhibition in interleukin-10(-/-) mice impaired colitis induced epithelial Akt and beta-catenin activation, reduced progenitor cell expansion, and prevented dysplasia. Human samples had increased numbers of progenitor cells with P-beta-catenin(552) throughout expanded crypts and increased messenger RNA expression of beta-catenin target genes in CUC, colitis associated cancer, tubular adenomas, and sporadic colorectal cancer, compared with control samples. CONCLUSIONS: PI3K-Akt signaling cooperates with Wnt to increase beta-catenin signaling during inflammation. PI3K-induced and Akt mediated beta-catenin signaling are required for progenitor cell activation during the progression from CUC to CAC; these factors might be used as biomarkers of dysplastic transformation in the colon. PMID- 20580722 TI - Hormone therapy in postmenopausal women affects hemispheric asymmetries in fine motor coordination. AB - Evidence exists that the functional differences between the left and right cerebral hemispheres are affected by age. One prominent hypothesis proposes that frontal activity during cognitive task performance tends to be less lateralized in older than in younger adults, a pattern that has also been reported for motor functioning. Moreover, functional cerebral asymmetries (FCAs) have been shown to be affected by sex hormonal manipulations via hormone therapy (HT) in older women. Here, we investigate whether FCAs in fine motor coordination, as reflected by manual asymmetries (MAs), are susceptible to HT in older women. Therefore, sixty-two postmenopausal women who received hormone therapy either with estrogen (E) alone (n=15), an E-gestagen combination (n=21) or without HT (control group, n=26) were tested. Saliva levels of free estradiol and progesterone (P) were analyzed using chemiluminescence assays. MAs were measured with a finger tapping paradigm consisting of two different tapping conditions. As expected, postmenopausal controls without HT showed reduced MAs in simple (repetitive) finger tapping. In a more demanding sequential condition involving four fingers, however, they revealed enhanced MAs in favour of the dominant hand. This finding suggests an insufficient recruitment of critical motor brain areas (especially when the nondominant hand is used), probably as a result of age-related changes in corticocortical connectivity between motor areas. In contrast, both HT groups revealed reduced MAs in sequential finger tapping but an asymmetrical tapping performance related to estradiol levels in simple finger tapping. A similar pattern has previously been found in younger participants. The results suggest that, HT, and E exposure in particular, exerts positive effects on the motor system thereby counteracting an age-related reorganization. PMID- 20580723 TI - An acute stressor alters steroid hormone levels and activity but not sexual behavior in male and female Ocoee salamanders (Desmognathus ocoee). AB - Stressors that are chronic have clear suppressive effects on reproductive behaviors in both males and females. Stressors that are acute have effects on reproductive behavior that are less clear. We measured the effects of an acute bout of handling in laboratory-housed male and female Ocoee salamanders (Desmognathus ocoee), a species with a prolonged mating season. Handling resulted in decreased locomotory activity and elevated plasma corticosterone, a hallmark of the vertebrate stress response. Handling also decreased plasma testosterone in males and elevated plasma estradiol in females. Despite the handling-induced changes in hormone levels, handling had minimal impact on courtship and mating. Other species in which reproduction is insensitive to acute stressors may live in extreme environments with limited reproductive opportunities, whereas Ocoee salamanders live in a relatively temperate environment with multiple reproductive opportunities. Together, these data indicate that an allostatic response to a stressor can alter locomotory activity and elevate corticosterone without suppressing nonessential behaviors like courtship and mating in a species in which reproductive opportunities can occur over a period of multiple months. The lack of reproductive suppression in Ocoee salamanders might be due to the low energetic cost of courtship and mating in this species combined with potentially elevated energetic stores, highlighting the importance of considering energy budgets when making predictions about behavioral effects of acute stressors. PMID- 20580721 TI - Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium. AB - BACKGROUND & AIMS: Factors that regulate enterocyte apoptosis in necrotizing enterocolitis (NEC) remain incompletely understood, although Toll-like receptor-4 (TLR4) signaling in enterocytes plays a major role. Nucleotide-binding oligomerization domain-2 (NOD2) is an immune receptor that regulates other branches of the immune system, although its effects on TLR4 in enterocytes and its role in NEC remain unknown. We now hypothesize that activation of NOD2 in the newborn intestine inhibits TLR4, and that failure of NOD2 signaling leads to NEC through increased TLR4-mediated enterocyte apoptosis. METHODS: The effects of NOD2 on enterocyte TLR4 signaling and intestinal injury and repair were assessed in enterocytes lacking TLR4 or NOD2, in mice with intestinal-specific wild-type or dominant-negative TLR4 or NOD2, and in mice with NEC. A protein array was performed on NOD2-activated enterocytes to identify novel effector molecules involved. RESULTS: TLR4 activation caused apoptosis in newborn but not adult small intestine or colon, and its intestinal expression was influenced by NOD2. NOD2 activation inhibited TLR4 in enterocytes, but not macrophages, and reversed the effects of TLR4 on intestinal mucosal injury and repair. Protection from TLR4 induced enterocyte apoptosis by NOD2 required a novel pathway linking NOD2 with the apoptosis mediator second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI (SMAC-DIABLO), both in vitro and in vivo. Strikingly, activation of NOD2 reduced SMAC-DIABLO expression, attenuated the extent of enterocyte apoptosis, and reduced the severity of NEC. CONCLUSIONS: These findings reveal a novel inhibitory interaction between TLR4 and NOD2 signaling in enterocytes leading to the regulation of enterocyte apoptosis and suggest a therapeutic role for NOD2 in the protection of intestinal diseases such as NEC. PMID- 20580725 TI - Genotypic interactions of renin-angiotensin system genes with diabetes type 2 in a Tunisian population. AB - AIMS: To explore the role of genetic variants of angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), and angiotensin type 1 receptor (AT1R A1166C) as predictors of diabetes risk and to examine their combined effects on type 2 diabetes mellitus (T2DM) patients. MAIN METHODS: One hundred and fourteen T2DM patients were compared to 175 healthy controls with similar age and sex. KEY FINDINGS: The genotypic frequencies for all three genes alone were significantly associated with increased risk of developing diabetes. Logistic regression analysis of classic coronary risk factors and the genetic polymorphisms demonstrated that hypertension and ACE DD genotype were the most significant contributors to T2DM. For the renin-angiotensin system (RAS) genes, the risk of T2DM in individuals with one risk genotype was 1.9 (95%CI: 1.1-3.0, p=0.017) higher than those with zero risk genotype. Individuals who carried two risk genotypes had a 4.0 (95%CI 1.7-9.4, p=0.001) times higher risk of T2DM than those who did not carry any risk genotypes of the RAS genes. Most interestingly, the risk of T2DM for individuals with three risk genotypes was 26.2 (95%CI: 5.8 117.9, p<0.001) higher than those with zero risk genotype. SIGNIFICANCE: The results of the present study imply that genotyping of renin-angiotensin system genes could become an important part of the clinical process of risk identification for T2DM in Tunisian population. PMID- 20580726 TI - Effect of vesicle traps on traffic jam formation in fast axonal transport. AB - The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon. PMID- 20580724 TI - Discoidin I from Dictyostelium discoideum and Interactions with oligosaccharides: specificity, affinity, crystal structures, and comparison with discoidin II. AB - Discoidin I (DiscI) and discoidin II (DiscII) are N-acetylgalactosamine (GalNAc) binding proteins from Dictyostelium discoideum. They consist of two domains: an N terminal discoidin domain and a C-terminal H-type lectin domain. They were cloned and expressed in high yield in recombinant form in Escherichia coli. Although both lectins bind galactose (Gal) and GalNAc, glycan array experiments performed on the recombinant proteins displayed strong differences in their specificity for oligosaccharides. DiscI and DiscII bind preferentially to Gal/GalNAcbeta1 3Gal/GalNAc-containing and Gal/GalNAcbeta1-4GlcNAcbeta1-6Gal/GalNAc-containing glycans, respectively. The affinity of the interaction of DiscI with monosaccharides and disaccharides was evaluated using isothermal titration calorimetry experiments. The three-dimensional structures of native DiscI and its complexes with GalNAc, GalNAcbeta1-3Gal, and Galbeta1-3GalNAc were solved by X ray crystallography. DiscI forms trimers with involvement of calcium at the monomer interface. The N-terminal discoidin domain presents a structural similarity to F-type lectins such as the eel agglutinin, where an amphiphilic binding pocket suggests possible carbohydrate-binding activity. In the C-terminal H-type lectin domain, the GalNAc residue establishes specific hydrogen bonds that explain the observed affinity (K(d)=3x10(-4) M). The different specificities of DiscI and DiscII for oligosaccharides were rationalized from the different structures obtained by either X-ray crystallography or molecular modeling. PMID- 20580727 TI - Lessons from models of pancreatic beta cells for engineering glucose-sensing cells. AB - Mathematical models of pancreatic beta cells suggest design principles that can be applied to engineering cells to sense glucose and secrete insulin. Engineering cells can potentially both contribute to future diabetes therapies and generate new insights into beta-cell function. The focus is on ion channels, Ca(2+)handling, and elements of metabolism that combine to produce the varied oscillatory patterns exhibited by beta cells. PMID- 20580728 TI - Measuring and modeling the oxygen profile in a nitrifying Moving Bed Biofilm Reactor. AB - In this paper we determine the oxygen profile in a biofilm on suspended carriers in two ways: firstly by microelectrode measurements and secondly by a simple mathematical model. The Moving Bed Biofilm Reactor is well-established for wastewater treatment where bacteria grow as a biofilm on the protective surfaces of suspended carriers. The flat shaped BiofilmChip P was developed to allow good conditions for transport of substrates into the biofilm. The oxygen profile was measured in situ the nitrifying biofilm with a microelectrode and it was simulated with a one-dimensional mathematical model. We extended the model by adding a CSTR equation, to connect the reactor to the biofilm through the boundary conditions. We showed the dependence of the thickness of the mass transfer boundary layer on the bulk flow rate. Finally, we estimated the erosion parameter lambda to increase the concordance between the measured and simulated profiles. This lead to a simple empirical relationship between lambda and the flow rate. The data gathered by in situ microelectrode measurements can, together with the mathematical model, be used in predictive modeling and give more insight in the design of new carriers, with the ambition of making process operation more energy efficient. PMID- 20580729 TI - Effects of damage to auditory cortex on the discrimination of speech sounds by rats. AB - The intensity of a noise-induced startle response can be reduced by the presentation of an otherwise neutral stimulus immediately before the noise ("prepulse inhibition" or PPI). We used a form of PPI to study the effects of damage to auditory cortex on the discrimination of speech sounds by rats. Subjects underwent control surgery or treatment of the auditory cortex with the vasoconstrictor endothelin-1. This treatment caused damage concentrated in primary auditory cortex (A1). Both before and after lesions, subjects were tested on 5 tasks, most presenting a pair of human speech sounds (consonant-vowel syllables) so that the capacity for discrimination would be evident in the extent of PPI. Group comparisons failed to reveal any consistent lesion effect. At the same time, the analysis of individual differences in performance by multiple regression suggests that some of the temporal processing required to discriminate speech sounds is concentrated anteroventrally in the right A1. These results also confirm that PPI can be adapted to studies of the brain mechanisms involved in the processing of speech and other complex sounds. PMID- 20580730 TI - Differential regulation of the bumetanide-sensitive cotransporter (NKCC2) by ovarian hormones. AB - The Na-K-2Cl cotransporter (NKCC2) regulates sodium transport along the thick ascending limb of Henle's loop and is important in control of sodium balance, renal concentrating ability and renin release. To determine if there are sex differences in NKCC2 abundance and/or distribution, and to evaluate the contribution of ovarian hormones to any such differences, we performed semiquantitative immunoblotting and immunoperoxidase immunohistochemistry for NKCC2 in the kidney of Sprague Dawley male, female and ovariectomized (OVX) rats with and without 17-beta estradiol or progesterone supplementation. Intact females demonstrated greater NKCC2 protein in homogenates of whole kidney (334+/ 29%), cortex (219+/-20%) and outer medulla (133+/-9%) compared to males. Ovarian hormone supplementation to OVX rats regulated NKCC2 in the outer medulla only, with NKCC2 protein abundance decreasing slightly in response to progesterone but increasing in response to 17-beta estradiol. Immunohistochemistry demonstrated prominent NKCC2 labeling in the apical membrane of thick ascending limb cells. Kidney section NKCC2 labeling confirmed regionalized regulation of NKCC2 by ovarian hormones. Localized regulation of NKCC2 by ovarian hormones may have importance in controlling sodium and water balance over the lifetime of women as the milieu of sex hormones varies. PMID- 20580731 TI - Isolation and characterization of a trypsin inhibitor from the skin secretions of Kaloula pulchra hainana. AB - Amphibian skin secretions contain many bioactive compounds. A trypsin inhibitor termed KPHTI was purified from the skin secretions of frog Kaloula pulchra hainana by successive ion-exchange and gel-filtration chromatography. KPHTI is a single chain glycoprotein, with an apparent molecular weight of 23 kDa in SDS PAGE. It is a competitive inhibitor and effectively inhibits trypsin catalytic activity on peptide substrate with the inhibitor constant (K(i)) value of 27 nM. KPHTI shows no inhibitory effect on chymotrypsin, thrombin, elastase, and subtilisin. The N-terminal sequence of KPHTI is DHEVTS, which shows no similarity with other known trypsin inhibitors. DTT apparently affected the inhibitory activity of KPHTI. But it was not sensitive to temperature and pH range, which suggested that it possessed stable trypsin inhibitory activity in natural environment, and maybe play an important role in against predators. PMID- 20580732 TI - Monocular depth effects on perceptual fading. AB - After prolonged viewing, a static target among moving non-targets is perceived to repeatedly disappear and reappear. An uncrossed stereoscopic disparity of the target facilitates this Motion-Induced Blindness (MIB). Here we test whether monocular depth cues can affect MIB too, and whether they can also affect perceptual fading in static displays. Experiment 1 reveals an effect of interposition: more MIB when the target appears partially covered by, than when it appears to cover, its surroundings. Experiment 2 shows that the effect is indeed due to interposition and not to the target's contours. Experiment 3 induces depth with the watercolor illusion and replicates Experiment 1. Experiments 4 and 5 replicate Experiments 1 and 3 without the use of motion. Since almost any stimulus contains a monocular depth cue, we conclude that perceived depth affects perceptual fading in almost any stimulus, whether dynamic or static. PMID- 20580733 TI - Lower reinforcing strength of the phenyltropane cocaine analogs RTI-336 and RTI 177 compared to cocaine in nonhuman primates. AB - Drugs that inhibit brain dopamine transporters (DAT) have been developed as potential agonist medications for cocaine abuse and dependence. Because the mechanism of action of such drugs is similar to cocaine, one concern regarding their use is the abuse potential of the medications themselves. The present study compared the reinforcing strength of cocaine (0.003-0.3mg/kg) and two 3 phenyltropane analogs of cocaine, RTI-336 (3beta-(4-chlorophenyl)-2beta-[3-(4' methylphenyl)isoxazol-5-yl]tropane hydrochloride; 0.003-0.1mg/kg) and RTI-177 (3beta-(4-chlorophenyl)-2beta-[3-phenylisoxazol-5-yl]tropane hydrochloride; 0.003 0.1mg/kg), using a progressive-ratio (PR) schedule in rhesus monkeys (n=4). PR schedules of reinforcement are frequently used to measure reinforcing strength of drugs. Earlier research using limited-access conditions reported that cocaine was a stronger reinforcer than either RTI-336 or RTI-177. Because the 3 phenyltropanes have longer durations of action, one purpose of the present study was to examine reinforcing strength using longer experimental sessions. Under these conditions, cocaine functioned as a reinforcer in all monkeys, and RTI-336 and RTI-177 functioned as a reinforcer in three of four subjects. Consistent with their documented slower onset of neurochemical and pharmacological effects, RTI 336 and RTI-177 were weaker reinforcers, resulting in fewer injections than cocaine. On average, the potencies of the two RTI compounds were not different than that of cocaine. These results support the view that slow-onset DA-selective uptake inhibitors have lower abuse liability than cocaine. In addition, the present findings suggest that changes in PR session length can influence potency comparisons between drugs, but not measures of reinforcing strength. PMID- 20580734 TI - Hedonic and motivational roles of opioids in food reward: implications for overeating disorders. AB - Food reward can be driven by separable mechanisms of hedonic impact (food 'liking') and incentive motivation (food 'wanting'). Brain mu-opioid systems contribute crucially to both forms of food reward. Yet, opioid signals for food 'liking' and 'wanting' diverge in anatomical substrates, in pathways connecting these sites, and in the firing profiles of single neurons. Divergent neural control of hedonic and motivational processes raises the possibility for joint or separable modulation of food intake in human disorders associated with excessive eating and obesity. Early findings confirm an important role for 'liking' and 'wanting' in human appetitive behaviors, and suggest the intriguing possibility that exaggerated signals for 'wanting,' and perhaps 'liking,' may contribute to forms of overeating. PMID- 20580736 TI - The association between commuter cycling and sickness absence. AB - OBJECTIVE: To study the association between commuter cycling and all-cause sickness absence, and the possible dose-response relationship between absenteeism and the distance, frequency and speed of commuter cycling. METHOD: Cross sectional data about cycling in 1236 Dutch employees were collected using a self report questionnaire. Company absenteeism records were checked over a one-year period (May 2007-April 2008). Propensity scores were used to make groups comparable and to adjust for confounders. Zero-inflated Poisson models were used to assess differences in absenteeism between cyclists and non-cyclists. RESULTS: The mean total duration of absenteeism over the study year was more than 1 day shorter in cyclists than in non-cyclists. This can be explained by the higher proportion of people with no absenteeism in the cycling group. A dose-response relationship was observed between the speed and distance of cycling and absenteeism. Compared to people who cycle a short distance (solvent-wetting method>surface attached method. The solid dispersions prepared by solvent evaporation appeared as an aggregated form with the amorphous form. In particular, the solid dispersion prepared by the solvent-evaporation method improved solubility about 900-fold and dissolution of tacrolimus 15-fold because of its reduced particle size, increased surface area and close contact between the hydrophilic carrier and the drug. In the solvent-wetting method, the drug, which was changed to an amorphous form, was attached onto the surface of undissolved carriers. However, the solid dispersion prepared by the surface-attached method gave an unchanged crystalline form. In this solid dispersion, the carriers were attached to the surface of the undissolved drug, resulting in changing the drug from being hydrophobic to hydrophilic. As the crystal form of drug in this solid dispersion was not converted to the amorphous form unlike other solid dispersions, it gave relatively less solubility and dissolution of the drug than did the others. Thus, in the development of a solid-dispersion system containing poorly water-soluble drugs, the method of preparation plays an important role in the solubility and crystallinity of the drugs. PMID- 20580798 TI - Efficient overcoming of drug resistance to anticancer nucleoside analogs by nanodelivery of active phosphorylated drugs. AB - One of the major problems in cancer chemotherapy is the fast development of drug resistance to most anticancer therapeutics. Thus, an important cause of the eventual decline in clinical efficacy of cytotoxic nucleoside analogs was the selection of resistant cancer cells with deficiencies in the expression of nucleoside transporters or nucleoside-activating kinases. Here, we present an efficient strategy of overcoming this type of drug resistance by tumor-specific delivery of nanogel-encapsulated active triphosphates of nucleoside analogs (NATP). The small particles of biodegradable cationic nanogels loaded with anionic NATP efficiently interacted with cancer cells and released active drug compounds into the cytoplasm. The potential of novel drug formulations was evaluated in the nucleoside transport-deficient (CEM/araC/C8) or nucleoside activation-deficient (RL7/G) lymphogenic cancer cells. Compared to nucleoside analogs, NATP-loaded nanogels demonstrated increased cytotoxicity, reducing the drug resistance index 250- to 900-fold in CEM/araC/C8 cells and 70- to 100-fold in RL7/G cells. The strong cytotoxic effect of nanoformulations was accompanied by characteristic cell cycle perturbations, usually observed in drug-treated sensitive cells, and resulted in the induction of apoptosis in all studied drug resistant cells. Efficient cellular accumulation of nanogels and the consequent increase in intracellular levels of NATP were found to be the major factors determining cytotoxic efficacy of nanoformulations. Decoration of nanogels with multiple molecules of tumor lymphatic-specific peptide (LyP1) enhanced the binding efficacy of nanocarriers with lymphogenic cancer cells. The targeted nanoformulation of activated gemcitabine (LyP1-NG-dFdCTP), when injected in subcutaneous RL7/G xenograft tumor model, demonstrated 2-fold more efficient tumor growth inhibition than gemcitabine at a higher dose. Nanogel-drug formulations exhibited no systemic toxicity during the treatment, hence extending the versatility of nucleoside analogs in the treatment of drug-resistant lymphogenic tumors. PMID- 20580800 TI - Effects of fluoroquinolones on CYP4501A and 3A in male broilers. AB - The inhibitory effects of fluoroquinolones on the enzyme activity, protein levels and mRNA expression of liver cytochrome P450 (CYP) 1A and 3A were investigated in male broiler chicks. Enrofloxacin (20 mg/kg), sarafloxacin (8 mg/kg) and marbofloxacin (5.5 mg/kg) were administrated in drinking water for 7 consecutive days. A cocktail of the probe drugs caffeine and dapsone was used to determine CYP1A and 3A activity. Western blot analysis and real-time PCR were used to determine the effects on protein levels of CYP1A and 3A, and on CYP1A4, 1A5, 3A37 mRNA levels. Enrofloxacin increased the half-life of elimination for both caffeine and dapsone, and decreased expression of CYP1A and 3A protein. Marbofloxacin decreased the metabolism of caffeine and expression of CYP1A protein. However, no change in mRNA expression was observed for any treatment group. This suggested that high doses of enrofloxacin and marbofloxacin, but not sarafloxacin, inhibit CYP in chick liver raising the possibility of drug-drug interaction when using these compounds. PMID- 20580801 TI - Modeling the electrode-neuron interface of cochlear implants: effects of neural survival, electrode placement, and the partial tripolar configuration. AB - The partial tripolar electrode configuration is a relatively novel stimulation strategy that can generate more spatially focused electric fields than the commonly used monopolar configuration. Focused stimulation strategies should improve spectral resolution in cochlear implant users, but may also be more sensitive to local irregularities in the electrode-neuron interface. In this study, we develop a practical computer model of cochlear implant stimulation that can simulate neural activation in a simplified cochlear geometry and we relate the resulting patterns of neural activity to basic psychophysical measures. We examine how two types of local irregularities in the electrode-neuron interface, variations in spiral ganglion nerve density and electrode position within the scala tympani, affect the simulated neural activation patterns and how these patterns change with electrode configuration. The model shows that higher partial tripolar fractions activate more spatially restricted populations of neurons at all current levels and require higher current levels to excite a given number of neurons. We find that threshold levels are more sensitive at high partial tripolar fractions to both types of irregularities, but these effects are not independent. In particular, at close electrode-neuron distances, activation is typically more spatially localized which leads to a greater influence of neural dead regions. PMID- 20580802 TI - Anti-fatigue activity of the water-soluble polysaccharides isolated from Panax ginseng C. A. Meyer. AB - AIM OF THE STUDY: Panax ginseng C. A. Meyer (ginseng) is a well-known Chinese herb often used in Asian countries for physical strength development. Ginseng polysaccharides are its active component and have a lot of pharmaceutical activities. However, anti-fatigue activity of ginseng polysaccharides has not yet been tested. The current study was designed to evaluate the anti-fatigue activity of ginseng polysaccharides (WGP) in an animal test for fatigue and compare the activities between the neutral (WGPN) and acidic (WGPA) portion in an attempt to determine whether the medicinal uses are supported by pharmacological effects. MATERIALS AND METHODS: WGP, WGPN and WGPA were orally administrated to mice once daily for 15 days. Anti-fatigue activity was assessed using the forced swim test (FST) and serum biochemical parameters were determined by autoanalyzer and commercially available kits. RESULTS: While all compounds were found to reduce immobility in the FST, the effect of WGPA was demonstrated in lower doses compared with WGP and WGPN. Moreover, the FST-induced reduction in glucose (GLU) and glutathione peroxidase (GPx) and increase in creatine phosphokinase (CK), lactic dehydrogenase (LDH) and malondialdehyde (MDA) levels, all indicators of fatigue, were inhibited by the corresponding doses of WGP, WGPN and WGPA. CONCLUSIONS: Ginseng polysaccharides have anti-fatigue activity, also reflected in the effects on the physiological markers for fatigue. The acidic polysaccharide is more potent than the neutral polysaccharide. PMID- 20580803 TI - Cerebralcare Granule, a Chinese herb compound preparation, improves cerebral microcirculatory disorder and hippocampal CA1 neuron injury in gerbils after ischemia-reperfusion. AB - AIM OF THE STUDY: Cerebralcare Granule (CG) is a Chinese herb compound preparation that has been used for treatment of cerebrovascular related diseases. However, the effect of post-treatment with CG on ischemia and reperfusion (I/R) induced cerebral injury is so far unclear. MATERIALS AND METHODS: In present study, cerebral global I/R was induced in Mongolian gerbils by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days, and CG (0.4 g/kg or 0.8 g/kg) was administrated 3h after the initiation of reperfusion. RESULTS: Post-treatment with CG for 5 days attenuated the I/R-induced production of hydrogen peroxide in, leukocyte adhesion to, and albumin leakage from cerebral microvessels, and, meanwhile, protected neuron from death, reduced the number of caspase-3- and Bax-positive cells, and increased Bcl-2-positive cells in hippocampal CA1 region. CONCLUSION: The results suggest that CG given after initiation of reperfusion is able to ameliorate cerebral microvascular dysfunction and hippocampal CA1 neuron damage caused by I/R. PMID- 20580804 TI - Pharmacokinetic properties of paeoniflorin, albiflorin and oxypaeoniflorin after oral gavage of extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba in rats. AB - AIM OF THE STUDY: To establish a HPLC-MS method and investigate the pharmacokinetic properties of paeoniflorin, albiflorin and oxypaeoniflorin and the pharmacokinetics difference of Radix Paeoniae Rubra and Radix Paeoniae Alba. MATERIALS AND METHODS: The extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba were separately administrated to rats. The concentrations of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma were determined by HPLC-ESI-MS method. The plasma samples were pretreated by protein precipitation with methanol and chromatographic separation was performed on a C(18) column with a mobile phase consisted of 0.1% formic acid and methanol (67:33, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning via electrospray ionization (ESI) source operating in the negative ionization mode. Main pharmacokinetic parameters were estimated and the total AUC of the three components were compared. RESULTS: The pharmacokinetic parameters of paeoniflorin, albiflorin and oxypaeoniflorin were significantly different. There was significant difference between the pharmacokinetic characteristics of Radix Paeoniae Rubra and Radix Paeoniae Alba. CONCLUSIONS: A specific and sensitive HPLC-ESI-MS method was developed for simultaneous determination of paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma and was successfully applied to pharmacokinetic study. The results might be helpful for the investigation of different effects of Radix Paeoniae Rubra and Radix Paeoniae Alba. PMID- 20580805 TI - Protective effect of Smilax glabra extract against lead-induced oxidative stress in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb. is a traditional Chinese herb, the rhizome of Smilax glabra has been used in folk medicine for the treatment of lead poisoning. AIMS OF THE STUDY: The present study was conducted to investigate the protective role of Smilax glabra extract (SGE) individually or combined with meso-2,3-dimercaptosuccinic acid (DMSA) against the effects of lead acetate on oxidative stress and lead burden in rats. MATERIALS AND METHODS: The biochemical parameters and enzymes in different treated rats were determined by commercial kits. The metal concentrations were measured using atomic absorption spectrophotometer. RESULTS: SGE (300 mg/kg) showed very low toxicity to organs in non-lead exposed rats. Administration of SGE individually had no effect on blood zinc protoporphyrin (ZPP) level but significantly enhanced the glutathione (GSH) content and delta-aminolevulinic acid dehydratase (ALAD), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in lead exposed rats. The co-treatment of SGE and DMSA had a synergism in increasing brain, liver and kidney superoxide dismutase (SOD), catalase (CAT) activities and GSH level, and decreasing oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS) levels. Moreover, the co-treatment could improve the hepatic and renal histopathology changes. SGE as chelating agent showed significant efficiency in reducing blood and tissue lead burden. CONCLUSIONS: The in vivo results suggested that SGE individually or combined with DMSA exhibited remarkable protective effects on lead-induced oxidative stress and lead burden in rats. PMID- 20580809 TI - Biodiesel production with immobilized lipase: A review. AB - Fatty acid alkyl esters, also called biodiesel, are environmentally friendly and show great potential as an alternative liquid fuel. Biodiesel is produced by transesterification of oils or fats with chemical catalysts or lipase. Immobilized lipase as the biocatalyst draws high attention because that process is "greener". This article reviews the current status of biodiesel production with immobilized lipase, including various lipases, immobilization methods, various feedstocks, lipase inactivation caused by short chain alcohols and large scale industrialization. Adsorption is still the most widely employed method for lipase immobilization. There are two kinds of lipase used most frequently especially for large scale industrialization. One is Candida antartica lipase immobilized on acrylic resin, and the other is Candida sp. 99-125 lipase immobilized on inexpensive textile membranes. However, to further reduce the cost of biodiesel production, new immobilization techniques with higher activity and stability still need to be explored. PMID- 20580808 TI - Novel rhamnolipid biosurfactants produced by a polycyclic aromatic hydrocarbon degrading bacterium Pseudomonas aeruginosa strain NY3. AB - A novel rhamnolipid biosurfactant-producing and Polycyclic Aromatic Hydrocarbon (PAH)-degrading bacterium Pseudomonas aeruginosa strain NY3 was isolated from petroleum-contaminated soil samples. Strain NY3 was characterized by its extraordinary capacity to produce structurally diverse rhamnolipids. A total of 25 rhamnolipid components and 37 different parent molecular ions, representing various metal ion adducts (Na(+), 2Na(+) and K(+)), were detected by matrix assisted laser desorption ionization time-of-flight mass spectrometry. Among these compounds are ten new rhamnolipids. In addition to its biosurfactant production, strain NY3 was shown to be capable of efficient degradation of PAHs as well as synergistic improvement in the degradation of high molecular weight PAHs by its biosurfactant. These findings have added novel members to the rhamnolipid group and expanded current knowledge regarding the diversity and productive capability of rhamnolipid biosurfactants from a single specific strain with variation of only one carbon source. Additionally, this paper lays the foundation for improvement in the yield of NY3BS and study of the degradation pathway(s) of PAHs in P. aeruginosa strain NY3. PMID- 20580810 TI - Genetic modification of critical enzymes and involved genes in butanol biosynthesis from biomass. AB - Interest in biobutanol, a sustainable vehicle fuel, is increasing due to rising oil prices and concerns of surrounding climate change and the energy crisis. However, the costs of biobutanol with conventional ABE fermentation by Clostridium are higher than the cost of butanol from today's petrochemical processes. Two major problems in the economic production of biobutanol are difficulty controlling the induction of a metabolic shift from acidogenesis to solventogenesis and limitations imposed by severe product inhibition. With developments in biotechnology, and the completion of genome sequencing of Clostridium, genetic modification is a viable method to improve the solvent yield and the butanol production ratio. The present article aims to highlight the latest research progress on overexpressing, inserting, knocking out, and knocking down genes of the key enzymes in the ABE fermentation pathway and other relative genes (such as genes coding for heat-shock proteins, operon, transcription, etc). Recombinant manipulations of these genes in Escherichiacoli and yeast have also been reported recently, although their butanol yields are lower than in Clostridium. Butanol production with solventogenic clostridia from various feedstocks is also evaluated in this review. PMID- 20580811 TI - Fluoride in drinking water and dental fluorosis. AB - In this study we determined the fluoride content in drinking water and hair of 12 year-old schoolchildren from different Serbian municipalities, i.e. Valjevo, Veliko Gradiste, Kacarevo and Vranjska Banja. The analyses were performed using composite fluoride ion-selective electrode. Average fluoride levels were 0.10, 0.15, 0.79 and 11 ppm in well water, 0.07, 0.10, 0.17 and 0.15 ppm in tap water, 19.3, 21.5, 25.4, and 32.5 ppm in hair samples, in Valjevo, Veliko Gradiste, Kacarevo and Vranjska Banja, respectively. Correlation analysis indicated statistically significant positive relationship between fluoride in wells water and fluoride in hair, for all municipalities: correlation coefficients were 0.54 (p < 0.05), 0.89, 0.97 and 0.99 (p < 0.001), in Vranjska Banja, Valjevo, Veliko Gradiste, and Kacarevo, respectively. Positive correlation was obtained also between fluoride in tap water and hair samples in all regions under the study, with statistical significance only in Valjevo municipality, p < 0.05. Dental examination of schoolchildren confirmed dental fluorosis only in the region of Vranjska Banja. Moreover, in endemic fluorotic region of Vranjska Banja, positive and statistically significant correlations were confirmed between fluoride in well water and dental fluorosis level (r = 0.61; p < 0.01) and additionally between fluoride in hair and dental fluorosis level (0.62; p < 0.01). The primary findings from this study have shown that fluoride content in hair is highly correlated with fluoride content in drinking water and dental fluorosis level, indicating that hair may be regarded as biomaterial of high informative potential in evaluating prolonged exposure to fluorides and to individuate children at risk of fluorosis regardless of the phase of teeth eruption. PMID- 20580812 TI - Comparison through a LCA evaluation analysis of food waste disposal options from the perspective of global warming and resource recovery. AB - This study evaluated feed manufacturing including dry feeding and wet feeding, composting, and landfilling for food waste disposal options from the perspective of global warming and resource recovery. The method of the expanded system boundaries was employed in order to compare different by-products. The whole stages of disposal involved in the systems such as separate discharge, collection, transportation, treatment, and final disposal, were included in the system boundary and evaluated. The Global Warming Potential generated from 1tonne of food wastes for each disposal system was analyzed by the life cycle assessment method. The results showed that 200kg of CO(2)-eq could be produced from dry feeding process, 61kg of CO(2)-eq from wet feeding process, 123kg of CO(2)-eq from composting process, and 1010kg of CO(2)-eq from landfilling. Feed manufacturing and composting, the common treatment methods currently employed, have been known to be environment friendlier than other methods. However, this study shows that they can negatively affect the environment if their by-products are not appropriately utilized as intended. PMID- 20580813 TI - Optimizing urothelial cell preparation for the human urinary micronucleus assay. AB - Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women's urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker. PMID- 20580814 TI - Finite element modelling and design of a concentration gradient generating bioreactor: application to biological pattern formation and toxicology. AB - This paper describes the use of a microfluidic gradient maker for the toxicological analysis of some conventional biomolecules such as hydrogen peroxide and a local anaesthetic, lidocaine on different cell cultures, human endothelial cells and myoblasts, respectively. The microfluidic device was designed and simulated using COMSOL Multiphysics and the concentration gradient in the microfluidic network was analysed through a fluid-dynamic and mass transport study. Subsequently the device was fabricated with soft lithography, casting PDMS in a master to obtain channels about 250 microm deep. Hydrogen peroxide was tested on human endothelial cells, while lidocaine was tested on C2C12 myoblasts and an analysis was performed using propidium iodide staining followed by an imaging processing routine to obtain quantitative dose-response profiles in the gradient maker. The results show that the Gradient Maker (GM) bioreactor is a more sensitive method for detection of cell toxicity, and compared with testing of drug toxicity using microwells with individual cell cultures, allows one shot testing with a single cell culture exposed to a large number of concentrations. Moreover, the Gradient Maker was also modelled in order to realise biological pattern formation using two morphogenes acting as activator and inhibitor with varying diffusion rates. PMID- 20580815 TI - Chromosomal conservation and sequence diversity of ribosomal RNA genes of two distant Oryza species. AB - Contrary to the chromosomal polymorphism of 45S ribosomal genes (45S rDNA) loci in other Oryza species, each of Oryza australiensis and Oryza brachyantha has only one 45S rDNA locus at the most conserved position of 45S rDNAs in Oryza. O. australiensis and O. brachyantha are known phylogenetically distant and have extremely different genome sizes among diploid Oryza species. This study reveals that the sequences and organizations of intergenic spacer (IGS) for 45S rDNA of both O. australiensis and O. brachyantha are different from other Oryza species. The IGS of O. australiensis contains 13 tandem repeats and only one transcriptional initiation site, while there are four tandem repeats and three transcriptional initiation sites in the IGS of O. brachyantha. Our results suggest different evolution processes of orthologous rDNA loci in the genus Oryza. Here we also demonstrate an efficient strategy to study locus-specific IGS before whole genome sequences data are available. PMID- 20580816 TI - YPEL5 protein of the YPEL gene family is involved in the cell cycle progression by interacting with two distinct proteins RanBPM and RanBP10. AB - YPEL5 is a member of the YPEL gene family that is highly conserved in the eukaryotic species and apparently involved in a certain cell division-related function. In this study, we examined the functional and phylogenetic aspects of YPEL5 protein in more detail. During cell cycle, YPEL5 protein was detected at different subcellular localizations; at interphase, it was located in the nucleus and centrosome, then it changed location sequentially to spindle poles, mitotic spindle, and spindle midzone during mitosis, and finally transferred to midbody at cytokinesis. Knockdown of YPEL5 function by siRNA or anti-sense morpholino oligonucleotide inhibited the growth of cultured COS-7 cells and early development of medaka fish embryos, indicating its involvement in cell cycle progression. Interestingly, RanBPM (Ran Binding Protein in the Microtubule organizing center, encoded by RANBP9) was identified as a YPEL5-binding protein by yeast two-hybrid method. A paralog of RanBPM, namely RanBP10 (encoded by RANBP10), was found to be another YPEL5-binding protein, and these two protein genes are highly conserved each other. Comparative genomic analysis allowed us to define a new gene family consisting of RanBPM and RanBP10, named Scorpin, providing a basis to better understand how they interact with YPEL5. PMID- 20580817 TI - Delayed manifestations of CNS effects in formerly exposed printers--a 20-year follow-up. AB - Whether long-term occupational exposure to organic solvents may affect mental and cognitive functioning later in life, remains unclear. In this study, twelve rotogravure printers formerly exposed to toluene and 19 referents, all initially examined in the mid-1980s, were reexamined after twenty years, applying neuropsychological tests, symptoms and social interaction questionnaires, medical examination, and exposure assessment of each individual's cumulative exposure. By far the most extensive exposure, mainly toluene, had occurred before 1985. The printers were found to have deteriorated more than their referents in cognitive functioning affecting reasoning and associative learning. No relevant additional exposure during the lengthy time period between assessments could explain this discrepancy. In addition, printers performed significantly worse than the referents in verbal memory and sustained attention at follow-up, where also a dose-effect relationship was noted for reasoning. While the printers did not report more subjective cognitive complaints than the referents, a slightly higher depression score was noted for the printers. The findings of significantly worse deteriorations in cognitive functioning in previously toluene-exposed printers are in line with our hypothesis that sub-clinical deficits during the working life may become manifest later in life, indicating that exposure may in fact interact with ageing. However, considering the small study groups the results must be interpreted with caution. PMID- 20580818 TI - Behavioral effects of subchronic inhalation of toluene in adult rats. AB - Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent. PMID- 20580819 TI - Caenorhabditis elegans, a pluricellular model organism to screen new genes involved in mitochondrial genome maintenance. AB - The inheritance of functional mitochondria depends on faithful replication and transmission of mitochondrial DNA (mtDNA). A large and heterogeneous group of human disorders is associated with mitochondrial genome quantitative and qualitative anomalies. Several nuclear genes have been shown to account for these severe OXPHOS disorders. However, in several cases, the disease-causing mutations still remain unknown. Caenorhabditis elegans has been largely used for studying various biological functions because this multicellular organism has short life cycle and is easy to grow in the laboratory. Mitochondrial functions are relatively well conserved between human and C.elegans, and heteroplasmy exists in this organism as in human. C. elegans therefore represents a useful tool for studying mtDNA maintenance. Suppression by RNA interference of genes involved in mtDNA replication such as polg-1, encoding the mitochondrial DNA polymerase, results in reduced mtDNA copy number but in a normal phenotype of the F1 worms. By combining RNAi of genes involved in mtDNA maintenance and EtBr exposure, we were able to reveal a strong and specific phenotype (developmental larval arrest) associated to a severe decrease of mtDNA copy number. Moreover, we tested and validated the screen efficiency for human orthologous genes encoding mitochondrial nucleoid proteins. This allowed us to identify several genes that seem to be closely related to mtDNA maintenance in C. elegans. This work reports a first step in the further development of a large-scale screening in C. elegans that should allow to identify new genes of mtDNA maintenance whose human orthologs will obviously constitute new candidate genes for patients with quantitative or qualitative mtDNA anomalies. PMID- 20580820 TI - The pronotum LIM-HD gene tailup is both a positive and a negative regulator of the proneural genes achaete and scute of Drosophila. AB - Early in the development of the imaginal wing disc of Drosophila, the LIM-HD gene tailup (islet), together with the HD genes of the iroquois complex, specify the notum territory of the disc. Later, tailup has been shown to act as a prepattern gene that antagonizes formation of sensory bristles on the notum of this fly. It has been proposed that Tailup downregulates the expression of the proneural genes achaete and scute by interfering with factors needed to activate these genes in the dorsocentral and scutellar regions of the disc. By means of a clonal analysis performed with tailup null alleles, here we show that, on the one hand, tailup is necessary to prevent formation of extra macrochaetae on most of the 11 sites where these landmark bristles arise on the fly notum. On the other hand, tailup is required to activate achaete and scute at the dorsocentral region, probably by acting as an hexameric complex with the cofactor Chip and the transcriptional activator Sspd on the dorsocentral enhancer of the achaete-scute complex. In contrast, in the scutellar region Tailup acts downstream of achaete-scute, antagonizing the proneural function of these genes probably in cooperation with Chip. We conclude that tailup acts on bristle development by several, even antagonistic, mechanisms. PMID- 20580821 TI - Grafted thermo-responsive gelatin microspheres as delivery systems in triggered drug release. AB - In this paper, a novel class of microspheric hydrogels was synthesized by grafting of N-isopropyacrylamide (NIPAAm) with gelatin. The possibility of inserting commercial gelatin in a crosslinked structure bearing thermo-sensitive moieties, by radical process, represents an interesting innovation that significantly improves the device performance, opening new applications in biomedical and pharmaceutical fields. This synthetic approach allows a modification of the polymeric network composition, producing hydrogels with suitable physico-chemical properties and a transition temperature higher than NIPAAm homopolymers. The incorporation of monomers into the network was confirmed by infrared spectroscopy, and the composition of the polymerization feed was found to strictly influence the network density and the shape of hydrogels. Thermal analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the temperature range 34.6-34.8 degrees C, according to the amount of the hydrophilic portions in the network. In order to test the preformed materials as drug carriers, diclofenac sodium salt was loaded into the spherical microparticles. After the determination of the drug entrapment percent, drug release profiles in media at different temperature were analysed. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribution was evaluated. PMID- 20580825 TI - Quantitative methods for structural characterization of proteins based on deep UV resonance Raman spectroscopy. AB - Here we report on novel quantitative approaches for protein structural characterization using deep UV resonance Raman (DUVRR) spectroscopy. Specifically, we propose a new method combining hydrogen-deuterium (HD) exchange and Bayesian source separation for extracting the DUVRR signatures of various structural elements of aggregated proteins including the cross-beta core and unordered parts of amyloid fibrils. The proposed method is demonstrated using the set of DUVRR spectra of hen egg white lysozyme acquired at various stages of HD exchange. Prior information about the concentration matrix and the spectral features of the individual components was incorporated into the Bayesian equation to eliminate the ill-conditioning of the problem caused by 100% correlation of the concentration profiles of protonated and deuterated species. Secondary structure fractions obtained by partial least squares (PLS) and least squares support vector machines (LS-SVMs) were used as the initial guess for the Bayessian source separation. Advantages of the PLS and LS-SVMs methods over the classical least squares calibration (CLSC) are discussed and illustrated using the DUVRR data of the prion protein in its native and aggregated forms. PMID- 20580823 TI - Enhanced cell accumulation and collagen processing by keratocytes cultured under agarose and in media containing IGF-I, TGF-beta or PDGF. AB - We previously showed an agarose overlay on keratocytes cultured in media containing pharmacological levels of insulin enhanced collagen processing and collagen fibril formation. In this study, we compared collagen processing by keratocytes cultured in media containing physiological levels of IGF-I, TGF-beta, FGF-2, and PDGF in standard and in agarose overlay cultures. Pepsin digestion/SDS PAGE was used to determine the levels of procollagen secreted into the media and the collagen content of the ECM associated with the cell layer. Distribution of collagen type I and fibronectin in the ECM of the agarose cultures was determined by immunoflorescence. Collagen fibril and keratocyte morphology was evaluated by electron microscopy. The agarose overlay significantly enhanced the cell number in the IGF-I, TGF-beta and PDGF treated cultures by 2-3 fold. The overlay also significantly enhanced the processing of procollagen to collagen fibrils from 29% in standard cultures to 63-68% in agarose cultures for the IGF-I and PDGF cultures, and from 66% in standard culture to 85% in agarose culture for the TGF beta cultures. Cell accumulation and collagen processing was not enhanced by agarose overlay of the FGF-2 treated cultures. Collagen type I and fibronectin were more uniformly distributed and the collagen fibrils smaller in the ECM of the TGF-beta treated cultures. Keratocytes in the FGF-2 treated cultures were in close cell contact with few collagen fibrils while IGF-I, TGF-beta, and PDGF cultures had an extensive ECM with abundant collagen fibrils. The results of this study indicate that the agarose overlay enhances collagen fibril assembly and cell accumulation by keratocytes when both collagen synthesis and cell proliferation are stimulated. PMID- 20580824 TI - Steroid metabolome in fetal and maternal body fluids in human late pregnancy. AB - Despite the extensive research during the last six decades the fundamental questions concerning the role of steroids in the initiation of human parturition and origin and function of some steroids in pregnancy were not definitely answered. Based on steroid metabolomic data found in the literature and our so far unpublished results, we attempted to bring new insights concerning the role of steroids in the sustaining and termination of human pregnancy, and predictive value of these substances for estimation of term. We also aimed to explain enigmas concerning the biosynthesis of progesterone and its bioactive catabolites considering the conjunctions between placental production of CRH, synthesis of bioactive steroids produced by fetal adrenal, localization of placental oxidoreductases and sustaining of human pregnancy. Evaluation of data available in the literature, including our recent findings as well as our new unpublished data indicates increasing progesterone synthesis and its concurrently increasing catabolism with approaching parturition, confirms declining production of pregnancy sustaining 5beta-pregnane steroids providing uterine quiescence in late pregnancy, increased sulfation of further neuroinhibiting and pregnancy sustaining steroids. In contrast to the established concept considering LDL cholesterol as the primary substrate for progesterone synthesis in pregnancy, our data demonstrates the functioning of alternative mechanism for progesterone synthesis, which is based on the utilization of fetal pregnenolone sulfate for progesterone production in placenta. Close relationships were found between localization of placental oxidoreductases and consistently higher levels of sex hormones, neuroactive steroids and their metabolites in the oxidized form in the fetus and in the reduced form in the maternal compartment. PMID- 20580826 TI - Prevalence of chronic fatigue among Chinese adults in Hong Kong: a population based study. AB - BACKGROUND: Epidemiologic data is available on chronic fatigue for Western, but not for Chinese populations. The aims of the present study were to determine the prevalence of chronic fatigue in the general population of Hong Kong, compare health and lifestyle characteristics of non-chronic fatigue and chronic fatigue cases, and identify risk factors for chronic fatigue. METHODS: We performed telephone interviews on 5001 randomly selected Chinese adults aged >=18 years administering the Chinese version of Chronic Fatigue Scale (ChCFS), the Hospital Anxiety and Depression Scale (HADS), and quality of life (QoL) indexed by Medical Outcomes Study 12-item Short-Form Health Survey (SF12). Lifestyle, and sociodemographic data were also collected. Chronic fatigue was defined according to Fukuda et al.'s (1994) criteria and case criterion was a ChCFS total scores >=4. RESULTS: The weighted prevalence of chronic fatigue was 10.7%, which was equivalent to 0.6 million adults in Hong Kong. Higher prevalence rates were found in females, older age groups, and low socioeconomic status. Fully adjusted stepwise regression analyses identified older age, retirees, housewife, existing long-term health problems, higher HADS scores, poor QoL, and low self-perceived health to be significantly associated with increased risk of chronic fatigue, whereas regular exercise was associated with decreased risk of chronic fatigue (all p<0.05). LIMITATIONS: The cross-sectional design did not allow determination of the time course and causal relationship between chronic fatigue and associated factors. CONCLUSIONS: Our data evidenced that chronic fatigue is common in the general population of Hong Kong, and the prevalence increased with age and was higher in the women and lower socioeconomic population. PMID- 20580827 TI - Effects of lamotrigine on hippocampal activation in corticosteroid-treated patients. AB - BACKGROUND: An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing's disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task related hippocampal activation in patients taking prescription corticosteroids. METHODS: A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). RESULTS: Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task related activation in the lamotrigine group as compared to the placebo group. LIMITATIONS: The modest sample size and an assessment period of only 24 weeks are study limitations. CONCLUSIONS: Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus. PMID- 20580828 TI - An inducible nitric oxide synthase (NOS) is expressed in hemocytes of the spiny lobster Panulirus argus: cloning, characterization and expression analysis. AB - Nitric oxide (NO) is a free radical gas involved in a variety of physiological processes in invertebrates, such as neuromodulation, muscle contraction and host defense. Surprisingly, little is known about the involvement of NO synthase (NOS) in the immune system of crustaceans. This work is focused on the study of the NOS gene of the spiny lobster Panulirus argus, a crustacean with commercial interest, and its relationship with the immune response to a microbial elicitor. A NOS full length DNA was isolated from hemocytes by reverse transcription-polymerase chain reaction (RT-PCR) using degenerated primers. The open reading frame (ORF) encodes a protein of 1200 amino acids, with an estimated molecular mass of 135.9 kDa, which contains the conserved domains and binding motifs of NOS found in a variety of organisms. NOS gene expression in lobster gills, heart, stomach, digestive gland, abdominal muscle, gut and hemocytes was studied by Real Time quantitative PCR (Real Time qPCR). The expression was higher in hemocytes, heart and gills. In addition, when lobster hemocytes were exposed in vitro to Escherichia coli O55:B5 lipopolysaccharide (LPS), an increase in the NOS activity and also in the NOS gene expression evaluated by Real Time qPCR was observed, thus demonstrating the presence of an inducible crustacean NOS by a microbial elicitor of the immune response. The information is relevant in providing basic knowledge for further studies of crustacean defense mechanisms. PMID- 20580829 TI - Tumor suppressor QM-like gene from disk abalone (Haliotis discus discus): molecular characterization and transcriptional analysis upon immune challenge. AB - We describe molecular characterization and transcriptional analysis of the gene encoding tumor suppressor QM-like protein, AbQM, in the disk abalone Haliotis discus discus. The full-length cDNA (765-bp) of AbQM was found to consist of a 654-bp ORF coding for a 218 amino acid protein of a 25 kDa molecular mass with a 10.2 isoelectric point. Analysis of AbQM sequence revealed the presence of characteristic motifs, including the ribosomal protein L10 signature, SH3-binding motif and two antibiotic binding sites. Phylogenetic analysis confirmed that AbQM is closely related to other mollusk QM proteins, and altogether they form a mollusk QM protein sub-family which displays evolutionary conservation from yeast to human. Tissue-specific expression and transcriptional regulation of AbQM was analyzed by quantitative real-time PCR in response to bacterial (Vibrio alginolyticus and Vibrio parahemolyticus, Listeria monocytogenes) and viral (viral hemorrhagic septicemia virus, VHSV) challenge. AbQM transcripts were found to be expressed ubiquitously in all examined tissues in a constitutive manner, as similar expression levels were detected in hemocytes, mantle, digestive tract and muscle. Upon bacterial and VHSV challenge, AbQM showed significant up-regulation in gills, but not in hemocytes. Taken together, these findings suggest that AbQM in abalone-like mollusks can respond to and facilitate a defensive effect against pathogenic infection. PMID- 20580830 TI - Effect of Withania somnifera (L. Dunal) root as a feed additive on immunological parameters and disease resistance to Aeromonas hydrophila in Labeo rohita (Hamilton) fingerlings. AB - The present study evaluated the efficacy of dietary doses of Withania somnifera (Ashwagandha) root powder on immunological parameters and disease resistance against the bacterial pathogen Aeromonas hydrophila infections in Indian major carp, Labeo rohita fingerlings. Fishes were fed with dry diet containing 0 gkg( 1) (control), 1 gkg(-1) (T(1)), 2 gkg(-1) (T(2)) and 3 gkg(-1) (T(3)) W. somnifera root powder for 42 days. Immunological (NBT level, Phagocytic activity, total immunoglobulin and lysozyme activity) parameters of fishes were examined at 0 days, 14 days, 28 days and 42 days of feeding. Fishes were challenged with A. hydrophila 42 days post feeding and mortalities (%) were recorded over 14 days post-infection. The results demonstrate that fishes fed with W. somnifera root showed enhanced NBT level, Phagocytic activity, total Immunoglobulin level and lysozyme activity (p<0.05) compared with the control group. The survivability was higher in experimental diets than the control group. Dietary W. somnifera at the level of 2 gkg(-1) showed significantly (P<0.05) higher protection (RPS 42.85+/ 0.65%) against A. hydrophila infection than control. The results suggest that the W. somnifera root powder have a stimulatory effect on immunological parameters and increases disease resistance in L. rohita fingerlings against A. hydrophila infection. PMID- 20580831 TI - Insight into the lymphoid organ of penaeid prawns: a review. AB - In crustacea, the lymphoid organ (LO) is found exclusively in penaeid prawns. Other crustaceans such as crabs, lobsters and crayfish do not possess lymphoid organs. Many scientists believe that the lymphoid organ is involved in defence against invading pathogens. The discovery of immune-related genes with the LO confirms some cells have immunological roles even though these genes might be from the haemocytes within this organ. The formation of the lymphoid organ spheroid (LOS) cells has been observed in many naturally or experimentally infected penaeid prawns with viral diseases. It has been suggested that these spheroid cells constitute a major site of viral degradation. The origin and elimination mechanism of the spheroids has been debated in a number of publications. It is most likely that this cell type is produced from exocytosed granular haemocytes and eliminated to the environment rather than in situ destruction via necrosis or apoptosis. PMID- 20580832 TI - Attempts at producing a hybridised Penaeus mondon cell line by cellular fusion. AB - The lack of a standardised system for the isolation, identification and purification of prawn viruses, is a major obstacle to the control of viruses in penaeid aquaculture. To date, spontaneous and induced transformation of somatic penaeid cells has failed. Hybrid cells with the aim of supporting the growth of penaeid viruses were created using polyethylene glycol (PEG)-mediated fusion with two immortal cell lines, Epithelioma papulosum cyprinid (EPC) and Spodoptera frugiperda pupal ovarian cells (Sf9), fused with Penaeus monodon haemocytes. The immortal cell lines were biochemically blocked with actinomycin D and puromycin before fusion occurred. A total of 78 hybrid clones were created. The methods used to confirm the presence of P. monodon genes and proteins in the hybrid cells did not detect crustacean components, nor was any viral amplification detected by real-time PCR after hybrid cells were inoculated with two P. monodon parvoviruses, Penaeus merguiensis densovirus and infectious hypodermal and haematopoietic necrosis virus. These results suggest although the creation of the hybrid cells appeared successful, the cell lines lacked key crustacean cell components required for their use as an in vitro system for virus replication. PMID- 20580833 TI - Comparative proteomic profiles of the hepatopancreas in Fenneropenaeus chinensis response to white spot syndrome virus. AB - White spot syndrome virus (WSSV) infects all shrimp species and is the greatest detriment to shrimp culture. To better understand the mechanism of molecular responses to WSSV infection in Chinese white shrimp Fenneropenaeus chinensis, two dimensional electrophoresis (2-DE) was used. Differentially expressed proteins in the hepatopancreas of control and WSSV-injected Chinese white shrimp between (6, 12 and 24 h post-injection) were screened. Quantitative intensity analysis and mass spectrometry revealed that 54 spots of 47 proteins were significantly up regulated, including some immune-related proteins, such as Toll receptor precursor, Leu-rich repeat protein, peroxinectin and serine proteinase-like protein. Fourteen spots of 13 proteins, such as heat shock protein, ATP synthase sub-unit beta and thrombospondin, were down-regulated in WSSV-infected shrimps. Protein expression patterns of the infected shrimp were drastically altered by WSSV infection. Some of the altered proteins were further investigated at the mRNA level using semi-quantitative reverse transcript PCR. These data may provide some information about shrimp proteins that participate in the WSSV infection process. PMID- 20580834 TI - Identification of upregulated immune-related genes in Vibrio harveyi challenged Penaeus monodon postlarvae. AB - A subtracted cDNA library was constructed and analyzed to elucidate the response of Penaeus monodon postlarvae challenged with Vibrio harveyi. As many as 960 randomly selected cDNA fragments generated through suppression subtractive hybridization were single pass sequenced. Forty five genes and 20 hypothetical proteins were identified, a few being first reports from shrimps. The most abundant immune relevant genes were ferritin, hemocyanin, and TCTP (translationally controlled tumor protein) indicating their upregulation as also confirmed through qPCR. Post-infection qPCR analyses confirmed 2.04, 2.09, 3.28, 5.49, 6.47, and 11.63 fold rise respectively in ferritin, penaeidin, MnSOD, lysozyme, TCTP, and hemocyanin genes. These genes may be involved in the regulation of the host defense against V. harveyi. PMID- 20580835 TI - Expression of cytokines IL-1beta and TNF-alpha in tissues and cysts surrounding Didymocystis wedli (Digenea, Didymozoidae) in the Pacific bluefin tuna (Thunnus orientalis). AB - Tuna long distance migrations and exposure to wide range of ambient water temperatures facilitate infections with several parasitic groups. This is reflected in the remarkable diversity of tuna parasite communities, especially members of Didymozoidae superfamily (Poche, 1907) (Trematoda, Digenea). Didymocystis wedli is the most frequent species encountered in bluefin tuna parasitizing gill filaments, therefore suggested as a biological marker to differentiate between discrete tuna Atlantic stocks. Because of its high occurrence in gill tissue and inflammatory reaction as the consequence, the aim of our study was to asses if inflammatory madiation through expression of IL 1beta and TNF-alpha is present locally at the site of D. wedli encystment, as well as if the systematic expression of cytokines can be detected in different tissues of infected versus uninfected fish. Quantification of localized cytokine expression was done on paraffine embedded gill sections by in situ hybridization, while quantitative PCR was used to mesured cytokine transcripts in skin mucus, kidney, spleen, gills and liver. Our results suggest that tuna constitutive expression of IL-1beta and TNF-alpha in gills and skin implies a well-adapted innate immunity present at the barrier between the organism and environment. Upregulation of both cytokines in Didymocystis-infected gills not followed by a systematic response evidences the ongoing of an inflammatory process specific for the parasitation site. However, the lack of intensive cytokines response to D. wedli observed by molecular and histological data that fails to eliminate the parasite, could be related to the "old" age of the parasitic process. PMID- 20580836 TI - Cognitive rigidity in unipolar depression and obsessive compulsive disorder: examination of task switching, Stroop, working memory updating and post-conflict adaptation. AB - Obsessive compulsive disorder (OCD) and depressive rumination are both characterized by cognitive rigidity. We examined the performance of 17 patients (9 suffering from unipolar depression [UD] without OCD, and 8 suffering from OCD without UD), and 17 control participants matched on age, gender, language and education, on a battery covering the four main executive functions. Results indicated that, across both disorders, patients required more trials to adjust to single-task conditions after experiencing task switching, reflecting slow disengagement from switching mode, and showed abnormal post-conflict adaptation of processing mode following high conflict Stroop trials in comparison to controls. Rumination, which was elevated in UD and not in OCD, was associated with poor working memory updating and less task preparation. The results show that OCD and UD are associated with similar cognitive rigidity in the presently tested paradigms. PMID- 20580837 TI - Impairment of emotional expression recognition in schizophrenia: a Cuban familial association study. AB - It is well established that schizophrenia is associated with difficulties in recognizing facial emotional expressions, but few studies have reported the presence of this deficit among their unaffected relatives. This study attempts to add new evidence of familial association on an emotional expression processing test. The study evaluated the performance of 93 paranoid schizophrenia patients, 110 first-degree relatives of probands from multiplex schizophrenia families, and 109 nonpsychiatric controls on a facial emotional recognition test using a computer morphing technique to present the dynamic expressions. The task entailed the recognition of a set of facial expressions depicting the six basic emotions presented in 21 successive frames of increasing intensity. The findings indicated that schizophrenia patients were consistently impaired for the recognition of the six basic facial expressions. In contrast, their unaffected relatives showed a selective impairment for the recognition of disgust and fearful expressions. Familial association of selective facial emotional expressions processing deficit may further implicate promising new endophenotypes that can advance the understanding of affective deficits in schizophrenia. PMID- 20580838 TI - Children with attention-deficit/hyperactivity disorder and autistic features: EEG evidence for comorbid disorders. AB - Attention-deficit/hyperactivity disorder (AD/HD) is the most common psychiatric disorder of childhood, although AD/HD is rarely the only diagnosis given to these children. Within the literature there is some debate as to whether it is valid to diagnose AD/HD with autism as a comorbid disorder, since the present diagnostic systems exclude the diagnosis of both disorders in the same child. The aim of this study was to determine whether electroencephalography (EEG) differences exist between two groups of children diagnosed with AD/HD, one scoring high (AD/HD+) and one scoring low (AD/HD-) on a measure of autism. The EEG was recorded during an eyes-closed resting condition from 19 electrodes, and Fourier transformed to provide absolute and relative power estimates in delta, theta, alpha and beta bands. Compared to age- and sex-matched controls, the AD/HD- group had increased absolute power in all frequency bands, somewhat higher relative theta activity and decreased relative delta. In comparison to the AD/HD- group, patients with autistic features (AD/HD+) had a number of qualitative differences in the beta and theta bands. These results indicate the presence of two comorbid conditions in the AD/HD+ group, which suggests that AD/HD and autism can occur in the same individual. PMID- 20580839 TI - Interactive effects of HIV/AIDS, body mass, and substance abuse on the frontal brain: a P300 study. AB - In view of the rising prevalence of an overweight body mass among patients living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), clinicians must now be mindful of possible adverse outcomes resulting from the co occurrence. The present study was designed to examine the additive and interactive effects of HIV/AIDS and an excess body mass, as well as the additional contributions of substance abuse or dependence. The dependent variable was brain function estimated by the measurement of P300 electroencephalographic potentials. P300 potentials were recorded during a task designed to elicit subcomponents with frontal (P300a) and both frontal and non-frontal (P300b) generators. Analyses revealed greater frontal P300a latencies among the 102 HIV-1 seropositive versus the 68 seronegative participants. In addition, frontal P300a latency was further increased by a synergistic interaction of HIV-1 serostatus with a body mass index (BMI)>=25 kg/m2. A history of substance abuse/dependence did not alter these changes. However, it did combine with HIV/AIDS to produce a smaller P300a amplitude than was seen in participants with neither disorder. The findings suggest that white matter changes accompanying an excess BMI may exacerbate those that attend HIV/AIDS and thereby slow down frontal brain function. Substance abuse, likewise, interacts with HIV/AIDS but may impair frontal brain function via a different mechanism. PMID- 20580840 TI - Twelve-month follow-up of family communication and psychopathology in children and adolescents with a first psychotic episode (CAFEPS study). AB - We analyzed the potential influence of family relationships and history of psychiatric disorders on the presentation and course of early psychotic disorders. We recruited 110 subjects aged 9-17 years with a first psychotic episode and 98 matched healthy controls, and followed them for 1 year. Data were collected through clinical interviews and the Parent-Adolescent Communication Inventory. A family history of psychosis-related disorders was more common in patients' families, with a five-fold higher risk for psychoses related disorders than families of healthy controls. If we consider psychoses related disorder in first-degree relatives, the risk is even higher, rising to 15-fold. The families of patients with a first psychotic episode score themselves worse in communication than the families of healthy controls. More problems in communication at baseline correlated with a higher degree of psychopathology and a lower clinical improvement after 12 months of follow-up. PMID- 20580841 TI - Admixture analysis of age at onset in bipolar disorder. AB - The aim of this study was to identify whether age at onset (AAO) identifies Bipolar Disorder (BD) subtypes, and to test whether the subgroups were confirmed by different clinical profiles. Admixture analysis was applied to determine a model that best fit the observed distribution of AAO in 964 BD patients. Three distributions of AAO were identified, and age means were 16.1 (S.D. 4.2), 25.4 (S.D. 2.5) and 32.2 (S.D. 9.5) years. A significant increased rate of suicide attempts, Bipolar I (BD I) caseness, and depressive onset was observed in the early-onset group when compared to those with later-onset by means of chi2. Findings from extant studies and our results are remarkably consistent in showing that BD can be subdivided into three groups based on AAO distributions, and that early-onset is associated with higher rates of suicide attempts. PMID- 20580842 TI - Assessment of stigma associated with attention-deficit hyperactivity disorder: psychometric evaluation of the ADHD stigma questionnaire. AB - This study evaluated the psychometric properties of the attention deficit hyperactivity disorder (ADHD) Stigma Questionnaire (ASQ) among a community sample of 301 adolescents ages 11-19 years at high (n=192) and low risks (n=109) for ADHD. Study subjects were drawn from a cohort study assessing ADHD detection and service use. The 26-item ASQ demonstrated good internal consistency. Confirmatory factor analysis using random parceling supported a three-factor structure with highly correlated subscales of disclosure concerns, negative self image, and concern with public attitudes, and a Schmid-Leiman analysis supported an overall stigma factor. Test-retest stability was assessed after two weeks (n=45) and found to be adequate for all three subscales. Construct validity was supported by relationships with related constructs, including clinical maladjustment, depression, self-esteem, and emotional symptoms, and the absence of a relationship with school maladjustment. Findings indicate that the ASQ has acceptable psychometric properties in a large community sample of adolescents, some of whom met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for ADHD. PMID- 20580843 TI - Pegylated human interferon alpha 2a does not induce depression-associated changes in mice. AB - Interferon (IFN) alpha proteins are proinflammatory cytokines having immunomodulating and antiviral properties. States during which cytokine systems are activated (e.g., during viral infection or during treatment of chronic hepatitis C and various malignancies with IFN alpha, etc.) can be associated with depression-like syndromes or even full-blown depressive episodes. Therefore, the role of IFN alpha and other cytokines in the pathogenesis of depressive disorder ("cytokine hypothesis of depression") has been assessed for many years with contradictory results. We have investigated whether intraperitoneal administration of high doses (up to 600 ug/kg body weight) of pegylated, recombinant human IFN alpha 2a in mice induces changes known to be associated with depression using three different readouts: behavior in a model of despair (Porsolt swim test), presence of anhedonia (sucrose preference test), and sensitivity of the hypothalamic-pituitary-adrenal system (dexamethasone suppression test). We also assessed potential IFN-induced changes in gene expression in the liver. In none of the performed experiments, depression associated effects could be found despite very high serum levels of IFN-induced antiviral activity compared to levels measured in hepatitis C virus (HCV) patients treated routinely with pegylated recombinant human IFN alpha 2a. The lack of such expected effects is probably due to the fact that pegylated human recombinant IFN alpha 2a does not activate the murine class I IFN receptor. Our results do not support the hypothesis that administration of recombinant pegylated human IFN alpha to mice produces a robust model of depression. PMID- 20580844 TI - Effects of memory training on cortical thickness in the elderly. AB - The brain's ability to alter its functional and structural architecture in response to experience and learning has been extensively studied. Mental stimulation might serve as a reserve mechanism in brain aging, but macrostructural brain changes in response to cognitive training have been demonstrated in young participants only. We examined the short-term effects of an intensive memory training program on cognition and brain structure in middle-aged and elderly healthy volunteers. The memory trainers completed an 8-week training regimen aimed at improving verbal source memory utilizing the Method of Loci (MoL), while control participants did not receive any intervention. Both the memory trainers and the controls underwent magnetic resonance imaging (MRI) scans and memory testing pre and post 8 weeks of training or no training, respectively. Cortical thickness was automatically measured across the cortical mantle, and data processing and statistical analyses were optimized for reliable detection of longitudinal changes. The results showed that memory training improved source memory performance. Memory trainers also showed regional increases in cortical thickness compared with controls. Furthermore, thickness change in the right fusiform and lateral orbitofrontal cortex correlated positively with improvement in source memory performance, suggesting a possible functional significance of the structural changes. These findings demonstrate that systematic mental exercise may induce short-term structural changes in the aging human brain, indicating structural brain plasticity in elderly. The present study included short-term assessments, and follow-up studies are needed in order to assess whether such training indeed alters the long-term structural trajectories. PMID- 20580845 TI - Action relationships concatenate representations of separate objects in the ventral visual system. AB - Objects in the real world are encountered in contexts where they interact together. Though it is known that neurons in the ventral visual stream mediate the recognition of individual objects, we have minimal knowledge of how multiple objects are processed at a neural level. We examined the neural response to pairs of objects using functional magnetic resonance imaging (fMRI). Objects positioned to interact together activated bilateral lateral occipital complex (LOC) and fusiform gyrus. This occurred irrespective of whether the objects were attended. In LOC, the effect of positioning objects for action was found regardless of whether the objects formed a familiar or unfamiliar action pair. In the fusiform gyrus activation was found when objects formed a familiar action pair. No changes were apparent in visuomotor (premotor and parietal) regions which might reflect a motor-based response to objects. These results show that ventral-stream regions respond to the interaction between objects, as well as to the sensory and functional properties of individual objects. PMID- 20580846 TI - Mechanisms and pathophysiology of the low-level blast brain injury in animal models. AB - The symptoms of primary blast-induced mTBI, posttraumatic stress disorder and depression overlap. Evidence of an organic basis for these entities has been scarce and controversial. We present a review of animal studies demonstrating that low-level blast causes pathophysiological and functional changes in the brain. We monitor a time period from minutes to approximately 1 week after blast exposure from multiple modes (air, underwater, localized and whole body). The most salient findings observed were (1) the peak pressures (P(max)) in the brain, elicited from the blast from the firing of military weapons (P(max) 23-45 kPa), have a similar magnitude as that registered in air close to the head. Corresponding measurements during the detonation pulse from explosives under water show a P(max) in the brain, which is only 10% of that in water outside the head. (2) The rise time of the pressure curve is 10 times longer in the brain as compared with the blast in air outside the head during firing of military weapons. (3) The lower frequencies in the blast wave appear to be transmitted more readily to the brain than the higher frequencies. (4) When animals are exposed to low levels of blast, the blast wave appears mostly transmitted directly to the brain during air exposure, not via the thorax or abdomen. (5) Low levels of blast cause brain edema, as indicated by increased bioelectrical impedance, an increase in the intracranial pressure, small brain hemorrhages and impaired cognitive function. PMID- 20580847 TI - Not a simple case - A first comprehensive phylogenetic hypothesis for the Midas cichlid complex in Nicaragua (Teleostei: Cichlidae: Amphilophus). AB - Nicaraguan Midas cichlids from crater lakes have recently attracted attention as potential model systems for speciation research, but no attempt has been made to comprehensively reconstruct phylogenetic relationships of this highly diverse and recently evolved species complex. We present a first AFLP (2793 loci) and mtDNA based phylogenetic hypothesis including all described and several undescribed species from six crater lakes (Apoyeque, Apoyo, Asososca Leon, Masaya, Tiscapa and Xiloa), the two great Lakes Managua and Nicaragua and the San Juan River. Our analyses demonstrate that the relationships between the Midas cichlid members are complex, and that phylogenetic information from different markers and methods do not always yield congruent results. Nevertheless, monophyly support for crater lake assemblages from Lakes Apoyeque, Apoyo, A. Leon is high as compared to those from L. Xiloa indicating occurrence of sympatric speciation. Further, we demonstrate that a 'three species' concept for the Midas cichlid complex is inapplicable and consequently that an individualized and voucher based approach in speciation research of the Midas cichlid complex is necessary at least as long as there is no comprehensive revision of the species complex available. PMID- 20580848 TI - Rituximab administration within 6 months of T cell-depleted allogeneic SCT is associated with prolonged life-threatening cytopenias. AB - The monoclonal anti-CD20 antibody Rituximab (RTX) is increasingly used in allogeneic stem cell transplantation (SCT) to treat lymphoproliferative disorders and chronic graft-versus-host disease (GVHD). RTX administration can be complicated by delayed and prolonged neutropenia, but the mechanism is unclear. We report the occurrence of profound cytopenias following RTX given in the conditioning regimen or early after T cell-deplete SCT to treat B cell lymphoproliferative disorders or chronic GVHD (cGVHD). Between 2006 and 2009, 102 patients (median age: 43 years, range: 13-68 years), received a myeloablative matched-sibling T cell-deplete SCT for lymphoid or myeloid hematologic disorders. Neutropenia occurring within 4 weeks of treatment developed in 16 of 17 patients given RTX within the first 190 days after SCT. Fourteen patients developed severe neutropenia (count <0.5 K/MUL) lasting up to 10 months and 12 required hospitalization to treat severe neutropenic infections. Six of the 14 patients died of infection complicating GVHD treatment. Recovery of lymphocytes and immunoglobulins was also delayed, with a significantly lower absolute lymphocyte counts (ALC) at 9 months and 12 months post-SCT compared to patients with cGVHD not treated with early RTX (P < .02). In contrast, patients receiving RTX 1 year after SCT experienced only moderate neutropenia 3 to 5 months after treatment lasting 10 to 20 days while maintaining absolute neutrophil count (ANC) >1.0 * 109/L. Although RTX rapidly controlled cGVHD, we conclude that its administration early after T cell-deplete SCT is associated with prolonged profound and life threatening cytopenias, and should be avoided. PMID- 20580851 TI - Influence of reproductive status, sex hormones and temperature on plasma IGF-I concentrations in sunshine bass (Morone chrysops x Morone saxatilis). AB - Insulin-like growth factor-I (IGF-I) concentrations in male and female sunshine bass (Morone chrysops x Morone saxatilis) were determined in March, early April, and late April in outdoor ponds at a commercial farm. Female fish were always larger than male fish; however, plasma IGF-I concentrations tended to be higher in male fish and increased as pond temperature and feeding increased in both sexes. Gonadal development was greatest in both sexes in March and declined to a regressed state by the end of April and the same pattern of change occurred with plasma estrogen and testosterone. Growth and IGF-I concentrations in sunshine bass fed estrogen, methyl testosterone, or a control diet were also determined. Growth was reduced in fish fed both sex hormones. Fish fed the control diet had the highest IGF-I levels, androgen-fed fish had intermediate levels, and estrogen fed fish had the lowest IGF-I concentrations after 4 weeks on the diet. Plasma IGF-I concentrations appeared to respond to increasing temperature in the ponds, and were inversely related to gonadal development and sex hormones. Exogenous sex hormones resulted in a decrease in plasma IGF-I, feeding activity and growth. PMID- 20580850 TI - A multigene molecular phylogenetic assessment of true morels (Morchella) in Turkey. AB - A collection of 247 true morels (Morchella spp.) primarily from the Mediterranean and Aegean Regions of Southern Turkey, were analyzed for species diversity using partial RNA polymerase I (RPB1) and nuclear ribosomal large subunit (LSU) rDNA gene sequences. Based on the result of this initial screen, 62 collections representing the full range of genetic diversity sampled were subjected to multigene phylogenetic species recognition based on genealogical concordance (GCPSR). The 62-taxon dataset consisted of partial sequences from three nuclear protein-coding genes, RNA polymerase I (RPB1), RNA polymerase II (RPB2), translation elongation factor (EF1-alpha), and partial LSU rDNA gene sequences. Phylogenetic analyses of the individual and combined datasets, using maximum parsimony (MP) and maximum likelihood (ML), yielded nearly fully resolved phylogenies that were highly concordant topologically. GCPSR analysis of the 62 taxon dataset resolved 15 putative phylogenetically distinct species. The early diverging Elata (black morels) and Esculenta Clades (yellow morels) were represented, respectively, by 13 and two species. Because a Latin binomial can be applied with confidence to only one of the 15 species (Morchella semilibera), species were identified by clade (Mel for Elata and Mes for Esculenta) followed by a unique Arabic number for each species within these two clades. Eight of the species within the Elata Clade appear to be novel, including all seven species within the Mel-20-to-31 subclade and its sister designated Mel-25. Results of the present study provide essential data for ensuring the sustainability of morel harvests through the formulation of sound conservation policies. PMID- 20580853 TI - Synthesis, antibacterial activity evaluation and QSAR studies of novel dispiropyrrolidines. AB - A series of novel dispiropyrrolidines have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from sarcosine and isatin with the dipolarophile 3-benzylidene-1-methyl-pyrrolidine-2,5-dione. Their antibacterial activity was evaluated against Bacillus subtilis NCIM 2718, Staphylococcus aureus NCIM5021, Salmonella typhi NCIM2501, Pseudomonas aeruginosa NCIM 5029 and Proteus vulgaris NCIM2813 by two fold dilution method. Compound 6e exhibits reasonably good activity and compound 6c exhibits poor activity against all the organisms. The QSAR's were developed for all antibacterial activities. The models had either one or two descriptors (r(2) = 0.81-0.97, r(adj)(2)=0.75-0.96, q(2) = 0.57-0.92, F-ratio = 12.73-162.76). Topology, shape, charge distribution and hydrophobic nature of the molecules had pronounced effect on their antibacterial activity. PMID- 20580852 TI - Maternal investment and nutrient use affect phenotype of American alligator and domestic chicken hatchlings. AB - Maternal investment by oviparous amniotes, in the form of yolk and albumen, and the mechanisms by which embryos use available energy and nutrients have a profound effect on embryo and, consequently, hatchling phenotype. Nutrient provisioning and uptake vary within and among oviparous taxa, avian and non-avian reptiles, due to differences and similarities in environment, behavior, and phylogeny. Eggs of crocodilians, the closest extant relatives to modern birds, are ideal models for examining modes of embryonic development, especially with regard to nutrient uptake, in non-avian reptiles and comparing them with those of birds. In this study, we investigated egg composition, embryo growth, and nutrient use in the domestic chicken (Gallus gallus) and American alligator (Alligator mississippiensis). We explored egg composition by separating and weighing components of fresh eggs. We measured embryo growth and nutrient usage by dissecting embryos and by obtaining samples of liquid from the amnion, digestive tract, and yolk sac throughout the last half of incubation. Variation in albumen mass contributed most to egg mass variation in chicken eggs, whereas alligator eggs were composed almost equally of yolk and albumen, although larger eggs contained proportionally more albumen and less yolk than smaller eggs. Both chicken and alligator albumen were mostly water (87% and 96%, respectively) although chicken albumen contained over three times more solid mass per gram than alligator albumen. In both species, yolk contained a high proportion of solids. Larger eggs produced larger hatchlings in both chickens and alligators, but albumen solids contributed to embryo mass only in chicken embryos. However, intact albumen proteins appeared in the stomach in embryos of both species. While the final disposition of albumen in alligators is unclear, variation in maternal investment of yolk at oviposition was responsible for nearly all of the variation in alligator hatchling phenotype, while both yolk and albumen contributed to chicken hatchling mass. PMID- 20580854 TI - Whole cell-ELISA to measure the gammaH2AX response of six aneugens and eight DNA damaging chemicals. AB - The phosphorylated form of the histone protein H2AX (gammaH2AX) plays a central role in sensing and repairing DNA damage and is a sensitive marker for DNA double strand breaks (DSB). Although a wide range of genotoxic agents that do not initiate DSB induce gammaH2AX, the range of chemicals that cause H2AX phosphorylation is not clear. We designed a novel, whole cell enzyme-linked immunosorbent assay (cell-ELISA) that can accurately quantify gammaH2AX levels and identify chemical compounds that induce gammaH2AX formation; our novel assay is more convenient than microscopic examination of gammaH2AX foci or flow cytometry. We measured gammaH2AX levels in CHL, CHO and V79 cells exposed to DNA damaging, non-genotoxic and aneugenic chemicals using the cell-ELISA assay. The cell-ELISA results for the DNA-damaging compounds (methyl methanesulfonate, N ethyl-N'-nitro-N-nitrosoguanidine, mitomycin C, cisplatin, irinotecan, etoposide, methotrexate and 5-fluorouracil) assayed showed that there was a concentration dependent increase in gammaH2AX, which was 1.5-fold greater than the negative control; the only exception was a negative response of CHO cells to 5 fluorouracil. None of the 10 non-genotoxic compounds assayed showed similar increases in gammaH2AX and all exhibited concentration-dependent growth inhibition of the cells. The highest levels of gammaH2AX found from treatment with aneugens (vincristine, colcemid, paclitaxel, griseofulvin, 17 allylaminogeldanamycin and CH3310395), which are compounds that cause spindle dysfunction and have no genotoxic activity in the Ames test, were 1.5-fold lower than the negative control. In contrast, mitomycin C and etoposide, which both have aneugenic and DNA-damaging activities, induced a positive response. None of the aneugens caused an increase in gammaH2AX at concentrations that induce micronuclei. The chemical classes that show positive results in the cell-ELISA are different from those that are positive in the Ames or in vitro micronucleus test. By using the cell-ELISA for the level of gammaH2AX, we were able to distinguish DNA-damaging agents from non-genotoxic compounds or aneugens. PMID- 20580855 TI - Relationship between spontaneous or radiation-induced apoptosis and telomere shortening in G(0) human lymphocytes. AB - To examine the correlation between spontaneous or radiation-induced apoptosis and telomere shortening, G(0) human peripheral blood lymphocytes were irradiated with X-rays and analyzed for viability, apoptosis, and telomere length. Part of the lymphocytes was kept under liquid-holding conditions for 48 h, and then loaded onto Ficoll-Paque medium to separate apoptotic (high-density) from normal (normal density) cells. Then all samples were examined for the same three end-points. To determine whether expression of p53 influences the telomere shortening associated with a spontaneous or radiation-induced apoptotic process, the lymphocytes were also analyzed for expression of p53 at 0 and 48 h recovery times (non-irradiated and irradiated samples) and after 2 weeks in liquid-holding conditions (non irradiated sample). After 48 h in liquid-holding, the p53-dependent apoptotic lymphocytes in the irradiated cultures presented shortened telomeres. After a 2 week recovery time, non-irradiated cells showed a p53-dependent spontaneous apoptosis, but no telomere shortening. These results demonstrate that radiation induced apoptosis correlates with shortened telomeres in G(0) human lymphocytes. Spontaneous and radiation-induced apoptosis are dependent on expression of p53. In contrast, p53 may not play an effective role in telomere shortening, because spontaneous apoptosis did not correlate with telomere shortening. As most tumours are compromised with respect to p53 function, our findings on the role of p53 in telomere shortening may prove critical for applying therapeutic modalities in the clinic, and may facilitate the design of agents that selectively disrupt telomere integrity in tumour cells. PMID- 20580849 TI - NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. AB - Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination, and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance posttransplant, better characterize the T cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify populations at very high risk for relapse to accelerate clinical development and avoid toxicity in patients not at risk for relapse. PMID- 20580856 TI - Linking hospital workers' organisational work environment to depressive symptoms: A mediating effect of effort-reward imbalance? The ORSOSA study. AB - Few studies have analysed the association between the organisational work environment and depression in hospital workers and we still have little understanding of how processes in the practice environment are related to depressive disorders. However, individual perception of an imbalance between efforts made and expected rewards has been associated with incident depression. The main goal of this study was to test the hypothesis that some organisational constraints at the work-unit level may be related to depressive symptoms in hospital workers, either directly or through individual perceptions of effort reward imbalance (ERI). In 2006, 3316 female registered nurses and nursing aids working in 190 work units in seven French university hospitals, recruited from the baseline screening of an epidemiological cohort study (the ORSOSA study), responded in 2006 to valid self-report questionnaires (CES-D, ERI). The organisational work environment was assessed with the self-rated Nursing Work Index - Extended Organisation (NWI-EO) aggregated at the work unit level. Multilevel models were used. We found that poor relations between workers within work units were associated with higher CES-D score, independently of perceived ERI. Low level of communication between workers in the unit was associated with individual perceptions of ERI and indirectly associated with depressive symptoms. Understaffing and non-respect of planned days off and vacations were associated with perceived ERI but these organisational constraints were not associated with depressive symptoms. Our study allowed us to identify and quantify organisational factors that have a direct effect on hospital workers' depressive symptoms, or an indirect effect through perceived ERI. Better understanding of the effect of organisational factors on health through perceived ERI would provide targets for successful interventions. Organisational approaches may be more effective in improving mental health at work and may also have a longer-lasting impact than individual approaches. PMID- 20580857 TI - Exploratory study of the impacts of Mutual Health Organizations on social dynamics in Benin. AB - The primary aim of Mutual Health Organizations (MHOs) is the financial protection of their members. However, given their community-based, participative and voluntary nature, it is conceivable that MHOs, as social organizations, would affect social dynamics. In an exploratory study in Benin, we studied social dynamics related to mutual aid, relationships of trust, and empowerment. Four MHOs, as contrasted cases, were selected from among the 11 in the region. Focus groups (n = 20) and individual interviews (n = 29) were conducted with members, non-members, and elected leaders of the four MHOs, and with professionals from the health facilities concerned. We carried out a qualitative thematic analysis of the content. Mutual aid practices, which pre-date MHOs, can be mobilized to promote MHO membership. Mutual aid practices are based on relationships of trust. The primary reason for joining an MHO is to improve financial accessibility to health services. Non-members see that members have a strong sense of empowerment in this regard, based on a high level of trust in MHOs and their elected leaders, even if their trust in health professionals is not as strong. Non-members share these feelings of confidence in MHOs and their leadership, although they trust health professionals somewhat less than do the members. The MHOs' low penetration rate therefore cannot be explained by lack of trust, as this study shows that, even with some distrust of the professionals, the overall level of trust in MHOs is high and MHOs and their leaders function as intermediaries with health professionals. Other explanatory factors are the lack of information available to villagers and, most especially, the problems they face in being able to pay the MHO premiums. PMID- 20580858 TI - The association of earnings with health in middle age: Do self-reported earnings for the previous year tell the whole story? AB - Research on earnings and health frequently relies on self-reported earnings (SRE) for a single year, despite repeated criticism of this measure. We use 31 years (1961-1991) of earnings recorded by the United States Social Security Administration (SSA) to predict the 1992 prevalence of disability, diabetes, stroke, heart disease, cancer, depression and death by 2002 in a subset of Health and Retirement Study participants (n = 5951). We compare odds ratios (ORs) for each health outcome associated with self-reported or administratively recorded earnings. Individuals with no 1991 SSA earnings had worse health in multiple domains than those with positive earnings. However, this association diminished as the time lag between earnings and health increased, so that the absence of earnings before approximately 1975 did not predict health in 1992. Among those with positive earnings, lengthening the lag between SSA earnings and health did not significantly diminish the magnitude of the association with diabetes, heart disease, stroke, or death. Longer lags did reduce but did not eliminate the association between earnings and both disability and depression. Despite theoretical limitations of single year SRE, there were no statistically significant differences between the ORs estimated with single-year SRE and those estimated with a 31-year average of SSA earnings. For example, a one unit increase in logged SRE for 1991 predicted a 19% reduction in the odds of dying by 2002 (OR = 0.81; 95% confidence interval: 0.72,0.90), while a similar increase in average SSA earnings for 1961-1991 had an OR of 0.72 (0.63, 0.82). The point estimates for the OR associated with 31 year average SSA earnings were further from the null than the ORs associated with single year SRE for heart disease, depression, and death, and closer to the null for disability, diabetes, and stroke, but none of these differences was statistically significant. PMID- 20580859 TI - Identification of novel markers for stem-cell niche of Arabidopsis shoot apex. AB - In Arabidopsis, shoot stem-cells give rise to all the aerial parts of plant body and are localized at the tip of the shoot apex. Feedback signaling mediated by CLAVATA3 (CLV3) and WUSCHEL (WUS), specify and maintain stem-cells in the shoot apical meristem (SAM). Although CLV3 and WUS have been used extensively as stem cell markers, their expression levels are mutually influenced by each other. Thus, CLV3 and WUS are not ideal markers for analyzing genes that function in this feedback regulation. Here, we present the expression profiles of genes that can be used as markers for cells of the stem-cell niche based on the following criteria: (1) they are expressed in cells of the central zone (CZ) or the rib meristem (RM)/organizing center (OC), (2) their expression levels are not influenced by alterations in CLV3 or WUS levels, and (3) their expression is initiated during embryonic stages and is maintained in post-embryonic development. By RNA in-situ hybridization, we also found that the expression of these genes follow two distinct patterns: (1) CLV3-like and (2) WUS-like. Moreover, the expression domains of these genes expand in SAMs of clv3 mutants, which accumulate higher numbers of stem-cells. A comprehensive expression patterns provided here suggests that they are ideal markers for stem-cell niche of Arabidopsis shoot apex. PMID- 20580860 TI - Kinetic and structural characterization of caspase-3 and caspase-8 inhibition by a novel class of irreversible inhibitors. AB - Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of information linking their functions to diseases. Through a structure-based drug design approach, a number of novel beta-strand peptidomimetic compounds were synthesized. Kinetic studies of caspase-3 and caspase-8 inhibition were carried out with these urazole ring containing irreversible peptidomimetics and a known irreversible caspase inhibitor, Z-VAD-fmk. Using a stopped-flow fluorescence assay, we were able to determine individual kinetic parameters of caspase-3 and caspase-8 inhibition by these inhibitors. Z-VAD-fmk and the peptidomimetic inhibitors inhibit caspase-3 and caspase-8 via a three-step kinetic mechanism. Inhibition of both caspase-3 and caspase-8 by Z-VAD-fmk and of caspase-3 by the peptidomimetic inhibitors proceeds via two rapid equilibrium steps followed by a relatively fast inactivation step. However, caspase-8 inhibition by the peptidomimetics goes through a rapid equilibrium step, a slow-binding reversible step, and an extremely slow inactivation step. The crystal structures of inhibitor complexes of caspases-3 and -8 validate the design of the inhibitors by illustrating in detail how they mimic peptide substrates. One of the caspase-8 structures also shows binding at a secondary, allosteric site, providing a possible route to the development of noncovalent small molecule modulators of caspase activity. PMID- 20580861 TI - Analysis of degradation data of poly(l-lactide-co-l,d-lactide) and poly(l lactide) obtained at elevated and physiological temperatures using mathematical models. AB - The degradation of resorbable polymeric devices often takes months to years. Accelerated testing at elevated temperatures is an attractive but controversial technique. The purposes of this paper include: (a) to provide a summary of the mathematical models required to analyse accelerated degradation data and to indicate the pitfalls of using these models; (b) to improve the model previously developed by Han and Pan; (c) to provide a simple version of the model of Han and Pan with an analytical solution that is convenient to use; (d) to demonstrate the application of the improved model in two different poly(lactic acid) systems. It is shown that the simple analytical relations between molecular weight and degradation time widely used in the literature can lead to inadequate conclusions. In more general situations the rate equations are only part of a complete degradation model. Together with previous works in the literature, our study calls for care in using the accelerated testing technique. PMID- 20580862 TI - Local attitudes on protected areas: evidence from three Natura 2000 wetland sites in Greece. AB - Environmental policies aimed at the conservation of protected areas are significantly influenced by social factors revealing the importance of investigating local knowledge and perceptions during their planning and implementation. The present article aims to explore perceptions and awareness of citizens in three protected areas of Greece: The National Park of Eastern Macedonia and Thrace, the Wetland of Kalloni, and Lake Tavropou. The survey explores perceptions of individuals on environmental issues and alternative management scenarios referring to management actors, funding sources, and management schemes for the conservation of biodiversity. Differences between the three research areas are also explored. According to the results of the study, citizens are in general supportive of protected areas and present relatively high levels of knowledge of environmental issues. However, environmental awareness is not accompanied by active participation for the resolution of environmental problems. By exploring differences between the three research areas, it is revealed that the provision of information significantly influences individuals' perceptions on relevant issues. Also, a significant finding of the study is that citizens are supportive of some forms of participatory management. It is essential, to encourage public participation and deliberation in order to promote their sustainable management. PMID- 20580863 TI - Physicochemical characterization of hydroxyapatite and its application towards removal of nitrate from water. AB - A laboratory study was conducted to investigate the efficiency of hydroxyapatite (HAP) towards removal of nitrate from synthetic nitrate solution. In the present research HAP synthesized from egg-shell was characterized using SEM, XRD, FTIR and TGA-DSC. The removal of nitrate was 96% under neutral conditions, using 0.3 g of adsorbent in 100 mL of nitrate solution having an initial concentration of 100 mg/L. An adsorption kinetic study revealed that the adsorption process followed first order kinetics. Adsorption data were fitted to a linearly transformed Langmuir isotherm with correlation coefficient (R(2))>0.98. Thermodynamic parameters were also calculated to study the effect of temperature on the removal process. In order to understand the adsorption type, equilibrium data were tested with the Dubinin-Radushkevich isotherm. The process was rapid and equilibrium was established within the first 40 min. PMID- 20580864 TI - Waste management with recourse: an inexact dynamic programming model containing fuzzy boundary intervals in objectives and constraints. AB - The existing inexact optimization methods based on interval-parameter linear programming can hardly address problems where coefficients in objective functions are subject to dual uncertainties. In this study, a superiority-inferiority-based inexact fuzzy two-stage mixed-integer linear programming (SI-IFTMILP) model was developed for supporting municipal solid waste management under uncertainty. The developed SI-IFTMILP approach is capable of tackling dual uncertainties presented as fuzzy boundary intervals (FuBIs) in not only constraints, but also objective functions. Uncertainties expressed as a combination of intervals and random variables could also be explicitly reflected. An algorithm with high computational efficiency was provided to solve SI-IFTMILP. SI-IFTMILP was then applied to a long-term waste management case to demonstrate its applicability. Useful interval solutions were obtained. SI-IFTMILP could help generate dynamic facility-expansion and waste-allocation plans, as well as provide corrective actions when anticipated waste management plans are violated. It could also greatly reduce system-violation risk and enhance system robustness through examining two sets of penalties resulting from variations in fuzziness and randomness. Moreover, four possible alternative models were formulated to solve the same problem; solutions from them were then compared with those from SI IFTMILP. The results indicate that SI-IFTMILP could provide more reliable solutions than the alternatives. PMID- 20580865 TI - Clostridium difficile infection in general surgery patients; identification of high-risk populations. AB - BACKGROUND: Risk factors associated with Clostridium difficile infection (CDI) in general surgical patients are poorly characterised. This study aimed to characterise the incidence and associations of C. difficile positivity (CDP) in general surgical inpatients to aid in the design of future policies regarding focused screening and risk-stratification mechanisms in this patient subpopulation. MATERIALS AND METHODS: Discharge, laboratory and coding data from all general surgery inpatients admitted to a large tertiary referral general surgical unit, between March 2005 and May 2007, were examined. RESULTS: 21,371 patient records were interrogated. 101 (0.47%) CDP cases were identified from laboratory records and compared with non-CDP controls for age, gender, length of stay (LOS), admission to intensive care unit or high dependency unit (ICU/HDU), co-morbidities and surgical procedures. Univariate analysis identified a range of risk factors associated with positivity. Multivariate analysis identified malignancy, gastrointestinal disease, anaemia, respiratory disease, circulatory disease, diabetes mellitus, those undergoing gastrointestinal surgery and increasing age to be independently associated with CDP status. CONCLUSIONS: This study identifies incidence and risk factor associations of those who tested CDP in a large contemporary general surgery inpatient population. Focused screening programmes based on high-risk populations may provide information on further risk factors and allow risk-stratification. Further healthcare worker education regarding risk factors may reduce the clinical impact of CDI by encouraging increased vigilance and therefore earlier detection. PMID- 20580866 TI - Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. AB - Baicalein is a widely used Chinese herbal medicine that has been used historically in anti-inflammatory and anti-cancer therapy. However, the molecular mechanism of its anti-cancer activity remains poorly understood and warrants further investigations. The purpose of this study is to verify the activity of baicalein to inhibit the invasion of MDA-MB-231 human breast cancer cells. The results indicated that baicalein suppressed MDA-MB-231 cell adhesion to fibronectin-coated substrate, wound healing migration and invasion through the Matrigel in a concentration-dependent manner. Western blot and gelatin zymography analysis showed that baicalein significantly inhibited the expression and secretion of matrix metalloproteinases 2/9 (MMP-2/9) in MDA-MB-231 cells. Additionally, treatment of MDA-MB-231 cells with baicalein down-regulated the expression of MMP-2/9 involved mitogen-activated protein kinases (MAPK) signaling pathway. Taken together, baicalein had potential to suppress the adhesion, migration and invasion of MDA-MB-231 cancer cells in vitro and it could serve as a promising drug for the treatment of cancer metastasis. PMID- 20580867 TI - Genistein and hematological malignancies. AB - Genistein is an isoflavanoid from soybeans and promising cancer chemotherapeutic agent. Genistein exposure varies widely because of cultural differences in diet. Hypothetically, this could account for differential cancer risk across ethnic populations. Genistein inhibits the growth of many different cancer cell lines by increasing apoptosis, inducing cell cycle delays, and modulating intracellular signaling pathways. Data from recent studies suggest that the therapeutic potential of genistein extends to cancers that affect blood, bone marrow, and lymph nodes. The objective of this paper is to provide background information on genistein, and discuss its potential as a therapeutic agent for treating hematological malignancies. PMID- 20580868 TI - HDAC inhibitors with different gene regulation activities depend on the mitochondrial pathway for the sensitization of leukemic T cells to TRAIL-induced apoptosis. AB - Epigenetic modifications commonly associated with tumor development, such as histone deacetylation, may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating gene transcription of components of the TRAIL signalling pathway. In the present study we have analyzed the effect of six different histone deacetylase inhibitors (HDACi), belonging to the four classic structural families, on TRAIL-induced apoptosis in leukemic T cell lines. Non-toxic and functional doses of all HDACi but apicidin, similarly sensitized different leukemic T cell lines to TRAIL induced apoptosis, while they showed no effect on the resistance of normal T lymphocytes. Sensitizing doses of vorinostat, valproic acid, sodium butyrate and MS-275 regulated the expression of TRAIL-R2, c-FLIP and Apaf-1 in leukemic cells while TSA modulated only the expression of Apaf-1. The synergistic effect of all HDACi and TRAIL was inhibited in Bcl-2-overexpressing leukemic T cells. Thus, different HDACi may affect the expression of different TRAIL-related genes, but regulation of the mitochondrial pathway seems to be essential for the TRAIL sensitizing effect of HDACi in leukemic T cells. Overall, HDACi represent a promising and safe strategy in combination with TRAIL for treatment of T-cell leukaemia. PMID- 20580869 TI - Activity and characterization of secondary metabolites produced by a new microorganism for control of plant diseases. AB - Microorganisms capable of utilizing vegetable tissues for growth in soils were isolated and their vegetable broth cultures were individually sprayed directly on leaves to test their ability to control Phytophthora blight of bell pepper caused by Phytophthora capsici. Liquid culture of Streptomyces strain TKA-5, a previously undescribed species obtained in this study, displayed several desirable disease control characteristics in nature, including high potency, long lasting and ability to control also black leaf spot of spoon cabbage caused by Alternaria brassicicolca. The extract was fungicidal to P. capsici but fungistatic to A. brassicicola. It was stable at high temperature and high pH. However, after exposure to pH 2 for 24h, the extract was no longer inhibitory to P. capsici although it was still strongly inhibitory to A. brassicicola. After treatment with cation or anion exchange resins, the extract lost its inhibitory effect against P. capsici but not A. brassicicola. The results suggest that the extract contained two different kinds of inhibitory metabolites, one against P. capsici with both positive and negative charges on its molecule and another against A. brassicicola with no charges on its molecule. The inhibitory metabolites were soluble in ethanol or methanol but not in water, ether or chloroform. They were dialyzable in the membrane tubing with molecular weight cut off of 10,000, 1000 or 500 but not 100, indicating that the inhibitors have a molecular weight between 500 and 100. Results also showed that both inhibitors are not proteins. PMID- 20580870 TI - Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12 month open-label phases. AB - This multicenter study assessed the safety and efficacy of teriparatide 20 microg/day in Japanese men and women with osteoporosis at high risk of fracture during a 12-month, randomized, double-blind, placebo-controlled treatment period followed by second and third treatment periods (to 18 and 24 months, respectively,) in which all subjects received open-label teriparatide. Subjects (93% female; median age 70 years) were randomized 2:1 to teriparatide versus placebo (randomized at baseline, teriparatide n=137, placebo-teriparatide n=70; entering the second period, teriparatide n=119, placebo-teriparatide n=59; entering the third period, teriparatide n=102, placebo-teriparatide n=50). For subjects with measurements at 12 months, teriparatide significantly increased bone mineral density (BMD) at the lumbar spine L2-L4 (mean percent change+/-SD, teriparatide 10.04+/-5.23% versus placebo-teriparatide 0.19+/-4.33%), the femoral neck (teriparatide 2.01+/-4.63% versus placebo-teriparatide 0.44+/-3.97%), and the total hip (teriparatide 2.72+/-4.04% versus placebo-teriparatide -0.26+/ 3.42%). In the placebo-teriparatide group at 24 months (12-month teriparatide dosing) BMD increased by 9.11+/-5.14% at the lumbar spine, 2.19+/-4.81% at the femoral neck and 2.46+/-3.54% at the total hip. In the teriparatide group at 18 and 24 months, BMD increased from baseline at the lumbar spine by 11.93+/-5.79% and 13.42+/-6.12%, respectively; at the femoral neck by 2.68+/-4.45% and 3.26+/ 4.25%, respectively; and at the total hip by 3.02+/-3.79% and 3.67+/-3.98%, respectively. Serum procollagen I N-terminal pro-peptide (PINP) increased rapidly with teriparatide treatment (P<0.001 versus placebo at 1 month) and changed from baseline in the teriparatide and placebo-teriparatide groups at 12 months by a median of 78.95% and -17.23%, respectively, (P<0.001) and at 24 months by 49.24% and 76.12%, respectively. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs were comparable in the teriparatide and placebo-teriparatide groups. These data show that teriparatide 20 microg/day was well tolerated and stimulated bone formation in Japanese subjects with osteoporosis at high risk of fracture during 18 and 24 months of treatment. PMID- 20580871 TI - Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: involvement of VEGF mechano-regulation. AB - Compromised angiogenesis appears to be a major limitation in various suboptimal bone healing situations. Appropriate mechanical stimuli support blood vessel formation in vivo and improve healing outcomes. However, the mechanisms responsible for this association are unclear. To address this question, the paracrine angiogenic potential of early human fracture haematoma and its responsiveness to mechanical loading, as well as angiogenic growth factors involved, were investigated in vitro. Human haematomas were collected from healthy patients undergoing surgery within 72 h after bone fracture. The haematomas were embedded in a fibrin matrix, and cultured in a bioreactor resembling the in vivo conditions of the early phase of bone healing (20% compression, 1 Hz) over 3 days. Conditioned medium (CM) from the bioreactor was then analyzed. The matrices were also incubated in fresh medium for a further 24 h to evaluate the persistence of the effects. Growth factor (GF) concentrations were measured in the CM by ELISAs. In vitro tube formation assays were conducted on Matrigel with the HMEC-1 cell line, with or without inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Cell numbers were quantified using an MTS test. In vitro endothelial tube formation was enhanced by CM from haematomas, compared to fibrin controls. The angiogenesis regulators, vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF beta1), were released into the haematoma CM, but not angiopoietins 1 or 2 (Ang1, 2), basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF). Mechanical stimulation of haematomas, but not fibrin controls, further increased the induction of tube formation by their CM. The mechanically stimulated haematoma matrices retained their elevated pro-angiogenic capacity for 24 h. The pro-angiogenic effect was cancelled by inhibition of VEGFR2 signalling. VEGF concentrations in CM tended to be elevated by mechanical stimulation; this was significant in haematomas from younger, but not from older patients. Other GFs were not mechanically regulated. In conclusion, the paracrine pro-angiogenic capacity of early human haematomas is enhanced by mechanical stimulation. This effect lasts even after removing the mechanical stimulus and appears to be VEGFR2 dependent. PMID- 20580872 TI - Use of a bioactive scaffold for the repair of bone defects in a novel reproducible vertebral body defect model. AB - Bone defects in vertebral bodies (VB) usually occur after the reduction of fractures or are caused by bone disease. Besides the treatment of original disease, repair of the bone defect can restore the structure of VB and improve stabilization of the spine to protect the spinal cord nerves. To aid studies of the efficacy of bioengineering techniques for repair of VB, we developed a rat model with a critical size bone defect in VB. Air-motivated burrs were used to create two sizes of bone defect (2 x 3 x 1.5 mm; 2 x 3 x 3 mm) in the anterior part of VB in 6-month-old Fischer 344 rats. Quantitative CT analyses and histological assays demonstrated that neither defects self-repaired by 8 weeks post surgery. Moreover, the tendency of bone formation was monitored in the same animal by serial CT image evaluations, allowing us to demonstrate that there was significant bone growth during the 4- to 6-week period after the creation of the bone defect. We then implanted sintered poly(lactic-co-glycolic acid) (PLGA) microsphere scaffolds loaded with Matrigel with or without recombinant human bone morphogenetic protein 2 (rhBMP2; 2.0 microg rhBMP2/10 microL Matrigel/scaffold) into the bone defect (2 x 3 x 3 mm) in the VB. Bone formation was detected by quantitative analyses of serial CT images, which demonstrated bone growth in rats that received the rhBMP2 implant, in both surrounding areas and inside area of the scaffold. In addition to a rapid increase within 2 weeks of the operation, another significant bone formation period was found between 4 and 8 weeks after the implantation. By contrast, the control group that received the implant without rhBMP2 did not show similar bone formation tendencies. The results of CT analyses were confirmed by histological studies. This study suggests that a critical size bone defect of the anterior VB can be developed in a rat model. Characterization of this model demonstrated that 4 to 6 weeks after creation of the defect was a significant bone growth period for VB bone repair in rats. This animal model has further utility for the study of different biomaterials for VB bone repair. Implantation of a bioactive PLGA scaffold carrying rhBMP2 allowed more successful repair of the VB defect. Although further characterization studies are needed, the bioactive PLGA scaffold developed in this study will likely adapt easily to other in vivo osteogenesis applications. PMID- 20580873 TI - Cowden syndrome. AB - Cowden syndrome (CS) is a rare inherited condition characterised by multiple hamartomas in a variety of tissues from all three embryonic layers. It is a cancer predisposition syndrome with an increased risk of developing malignancy in many tissues but especially breast, thyroid and endometrium. It is inherited in an autosomal dominant manner with ~80% of patients having a germ-line mutation of the PTEN tumour suppressor gene. Presenting signs and symptoms are highly non specific. Nevertheless clinicians should be able to recognise this syndrome so that patients may be screened for cancerous growths and afforded the opportunity to have genetic testing to assist them and their family members in making medical management decisions. We present a review of this unusual but important condition with particular emphasis on the diagnostic criteria, clinical features, genetics, management and surveillance. PMID- 20580874 TI - The unreasonable effectiveness of my self-experimentation. AB - Over 12 years, my self-experimentation found new and useful ways to improve sleep, mood, health, and weight. Why did it work so well? First, my position was unusual. I had the subject-matter knowledge of an insider, the freedom of an outsider, and the motivation of a person with the problem. I did not need to publish regularly. I did not want to display status via my research. Second, I used a powerful tool. Self-experimentation about the brain can test ideas much more easily (by a factor of about 500,000) than conventional research about other parts of the body. When you gather data, you sample from a power-law-like distribution of progress. Most data helps a little; a tiny fraction of data helps a lot. My subject-matter knowledge and methodological skills (e.g., in data analysis) improved the distribution from which I sampled (i.e., increased the average amount of progress per sample). Self-experimentation allowed me to sample from it much more often than conventional research. Another reason my self experimentation was unusually effective is that, unlike professional science, it resembled the exploration of our ancestors, including foragers, hobbyists, and artisans. PMID- 20580875 TI - Female authorship in emergency medicine parallels women practicing academic emergency medicine. AB - BACKGROUND: Studies have shown that women in emergency medicine (EM) lag behind their male counterparts in academic productivity. OBJECTIVES: We compared the proportion of female attending physicians from EM academic programs to the proportion of female first or second authors of original scientific manuscripts and case reports from four major EM journals in a single year. METHODS: We used a retrospective cross-sectional design. Original scientific manuscripts and case reports from four major EM journals published in 2005: Academic Emergency Medicine, Annals of Emergency Medicine, American Journal of Emergency Medicine, and Journal of Emergency Medicine were reviewed to determine genders of first and second authors. The proportion of female first or second authorship was then compared to the proportion of female EM attending physicians from 134 academic EM programs in the United States. Data were analyzed using Pearson's chi-squared and Clopper-Pearson binomial confidence intervals as appropriate. A p-value of <= 0.05 was considered significant. RESULTS: The percentage of female faculty; 940/3571 (26.32%, 95% confidence interval [CI] 24.9-27.8%) vs. the percentage of female first or second authorship 289/1123 (25.73%, 95% CI 23.3-28.4%) was not statistically significant (p = 0.562). There was no difference in the proportion of male and female authors with multiple manuscripts (p = 0.889). CONCLUSIONS: As measured by first and second authorship, there was no discrepancy between the proportion of female EM faculty and the proportion of female authorship in EM literature from 2005. PMID- 20580876 TI - Hospice and palliative medicine: a novel subspecialty of emergency medicine. AB - BACKGROUND: Emergency Medicine (EM) is a resuscitative discipline where the major focus in teaching and practice is to rapidly diagnose, stabilize, and initiate curative therapy. Thus, it may seem counterintuitive to have Hospice and Palliative Medicine (HPM), a specialty often perceived as a last resort measure "when no more can be done" for the patient, included as the latest subspecialty of EM. OBJECTIVE: We discuss the scope of practice and the role of HPM in the emergency department (ED) to clarify some commonly held misconceptions. DISCUSSION: HPM principles are frequently applied in ED patient care. EM clinicians routinely rely on many of the same skills that are refined and advanced by HPM when treating symptoms, facilitating goals of care discussions, communicating bad news, and integrating the treatment of the physical, psychological, and social suffering in patient care. The HPM approach to care is patient-centered as opposed to disease-centered, with a focus on the relief of distressing symptoms to improve the quality of life. This parallels ED care, where priority is given to alleviate distressing symptoms such as acute pain or vomiting, regardless of the underlying disease process. In fact, EM is one specialty in which we may submit a bill purely based on an International Classification of Diseases-9(th) Revision symptom code. CONCLUSION: In this article we explore the background of HPM; outline the principles and core skills of HPM that are applicable to the daily practice of EM; and explore the pathway, now available, towards a subspecialty certification. PMID- 20580877 TI - Rapid progression of Wellens syndrome in the emergency department. AB - BACKGROUND: In 1982, Wellens and colleagues described characteristic electrocardiogram (ECG) findings in angina patients virtually pathognomonic for significant stenosis of the proximal left anterior descending coronary artery and associated with a high risk of acute anterior wall myocardial infarction. CASE REPORT: We present the case of a 74-year-old emergency department patient with classic ECG findings of Wellens syndrome and progression to acute ST elevation within 55 min. SUMMARY: We present this case to increase awareness among emergency physicians of the characteristic findings of Wellens syndrome. PMID- 20580878 TI - Bilateral sciatic nerve palsy: a new presentation of toilet bowl neuropathy. AB - BACKGROUND: Presentations of lower extremity compression palsies are rare and exist only in case reports. The true incidence of emergency department (ED) presentations of bilateral sciatic nerve palsy, "toilet bowl neuropathy," is unknown. The following is a case of a 28-year-old active duty Navy woman who presented to our ED via ambulance with bilateral sciatic nerve palsy from prolonged immobility. OBJECTIVES: This discussion reviews the historical precedence for the diagnosis and details the work-up and prognosis. CASE REPORT: The patient presented complaining of bilateral lower extremity swelling, numbness, and an inability to walk after a prolonged, medication-facilitated sleep in an unusual position. She had significant weakness on examination and was admitted for further evaluation and care. Specialized neurologic studies were consistent with bilateral sciatic nerve palsy. CONCLUSION: Bilateral sciatic nerve palsy is an uncommon cause of lower extremity weakness. In the ED, other diagnoses such as Guillain-Barre syndrome, cauda equina, disk herniation, and gluteal compartment syndrome should be considered initially. The diagnosis of toilet bowl neuropathy, however, is dependent on obtaining an accurate history. This case report adds another perspective to the literature on sciatic nerve palsy recognition, diagnosis, and prognosis. PMID- 20580879 TI - Traumatic hemobilia without liver parenchymal injury due to blunt trauma. PMID- 20580880 TI - A new local-global approach for classification. AB - In this paper, we propose a new local-global pattern classification scheme that combines supervised and unsupervised approaches, taking advantage of both, local and global environments. We understand as global methods the ones concerned with the aim of constructing a model for the whole problem space using the totality of the available observations. Local methods focus into sub regions of the space, possibly using an appropriately selected subset of the sample. In the proposed method, the sample is first divided in local cells by using a Vector Quantization unsupervised algorithm, the LBG (Linde-Buzo-Gray). In a second stage, the generated assemblage of much easier problems is locally solved with a scheme inspired by Bayes' rule. Four classification methods were implemented for comparison purposes with the proposed scheme: Learning Vector Quantization (LVQ); Feedforward Neural Networks; Support Vector Machine (SVM) and k-Nearest Neighbors. These four methods and the proposed scheme were implemented in eleven datasets, two controlled experiments, plus nine public available datasets from the UCI repository. The proposed method has shown a quite competitive performance when compared to these classical and largely used classifiers. Our method is simple concerning understanding and implementation and is based on very intuitive concepts. PMID- 20580881 TI - Gene expression abnormalities and oligodendrocyte deficits in the internal capsule in schizophrenia. AB - Deficits in the expression of oligodendrocyte (Ol) and myelin genes have been described in numerous brain regions in schizophrenia (SZ) in association with abnormalities of cell cycle markers. We have previously reported a SZ-associated decrease in the expression of genes expressed after, but not prior to, the terminal differentiation of Ols in the posterior limb of the internal capsule (ICp). This pattern of deficits could reflect a failure of Ol precursors to exit the cell cycle and differentiate to meet the demands imposed by the high rate of apoptosis among myelinating Ols. Here we explore this hypothesis using quantitative real time PCR to examine the mRNA expression of additional genes in the ICp of the previously examined sample of 14 subjects with SZ and 15 normal controls (NCs). The genes examined in the present study were chosen because they are associated with particular phases of the cell cycle (CCND1, CCND2, p21(Cip1), p27(Kip1), and p57(Kip2)), with DNA replication and repair (PCNA), apoptosis (CASP3), or the Notch signaling pathway (JAG1, HES1, HES5, andDTX1). The Notch pathway influences whether Ol precursors continue to proliferate or exit the cell cycle. We also determined the densities of Ols in the ICp. Genes associated with maintenance of the cell cycle tended to exhibit increased expression levels in SZ relative to NCs and to be negatively correlated with the expression levels of the previously assessed mature Ol genes. In contrast, genes associated with cell cycle arrest tended to show the opposite pattern (decreased expression in SZ and positive correlations with mature Ol genes). CASP3 and PCNA expression levels were significantly decreased in SZ and positively correlated with mature Ol genes, suggesting that myelinating Ols may turnover more rapidly in normal controls than in subjects with SZ. JAG1 expression was significantly increased in SZ and exhibited positive correlations with mediators of the canonical Notch pathway but negative correlations with mature Ol genes. Ol densities were significantly decreased in SZ. These data are consistent with the hypothesis that Ol and myelin deficits in SZ involve a failure of Ol precursors to appropriately exit the cell cycle in order to differentiate and mature into myelinating Ols. PMID- 20580882 TI - Spontaneous regression of thoracic malignancies. AB - BACKGROUND: Clinicians are frequently questioned by patients about the possibility of spontaneous regression of tumors. Although there are many reports and a few case series documenting spontaneous regression, there is concern that these cases may not represent true regression. Using specific criteria, we attempted to determine the incidence and types of thoracic malignancy most likely to regress spontaneously. METHODS: We used a PubMed search of the phrase "spontaneous regression of thoracic lesions" reported from 1951 to December 2008. Using a modified Everson and Cole criterion we developed to define spontaneous regression, this search was refined for true spontaneous regression of primary and metastatic thoracic malignancies. RESULTS: Only 5 cases in the literature involved spontaneous regression of a primary thoracic malignancy. These include pleural mesothelioma, primary lung cancer and adenoid cystic carcinoma. 71 cases involved true spontaneous regression of metastatic thoracic neoplasms, of which 5 cases showed regression of the primary extrapulmonary tumors along with the pulmonary metastasis. Thoracic metastasis from renal cell carcinoma was the most common malignancy found to regress spontaneously. CONCLUSION: Spontaneous regression of primary thoracic malignancy is rare. Renal cell carcinoma accounts for most reported cases. PMID- 20580883 TI - Evolution of organic matter fractions after application of co-compost of sewage sludge with pruning waste to four Mediterranean agricultural soils. A soil microcosm experiment. AB - The effect of co-compost application from sewage sludge and pruning waste, on quality and quantity of soil organic carbon (SOC) in four Mediterranean agricultural soils (South Spain), was studied in soil microcosm conditions. Control soil samples (no co-compost addition) and soils treated with co-composts to a rate equivalent of 140 Mg ha(-1) were incubated for 90 days at two temperatures: 5 and 35 degrees C. The significances of incubation temperature and the addition of co-compost, on the evolution of the different fractions of SOC, were studied using a 2(3) factorial design. The co-compost amendment increased the amounts of humic fractions: humic acids (HA) (1.9 times), fulvic acids (FA) (3.3 times), humin (1.5 times), as well as the free organic matter (1.4 times) and free lipids (21.8 times). Incubation of the soils enhanced its biological activity mainly in the amended soils and at 35 degrees C, leading to progressive SOC mineralization and humification, concomitant to the preferential accumulation of HA. The incubation results show large differences depending on temperature and soil types. This fact allows us to select suitable organic amendment for the soil when a rapid increase in nutrients through mineralization is preferred, or in cases intending the stabilization and preservation of the SOC through a process of humification. In soils with HA of more than 5 E(4)/E(6) ratio, the incubation temperature increased rates of mineralization and humification, whereas lower temperatures limited the extent of both processes. In these soils the addition of co-compost in spring or summer is the most recommendable. In soils with HA of lower E(4)/E(6) ratio (<5), the higher temperature favoured mineralization but not humification, whereas the low temperature maintained the SOC levels and even increased the HA/FA ratio. In these soils the moment of addition of organic amendment should be decided depending on the effect intended. On the other hand, the lower the SOC content in the original soil, the greater are the changes observed in the SOC after amendment with co-compost. The results suggest that proper recommendations for optimum organic matter evolution after soil amendment is possible after considering a small set of characteristics of soil and the corresponding soil organic matter fractions, in particular HA. PMID- 20580886 TI - Navigated reconstruction of a tibial plateau compression fracture post-virtual reconstruction: a case report. AB - Post-traumatic arthrosis is a common problem following tibial plateau fractures. Computed tomography (CT) with 3D reconstruction is essential in facilitating accurate analysis of the fracture type and depth of compression, but is typically only available pre- or postoperatively. Special reconstruction software tools, based on 3D imaging, have been developed. Limiting factors include a lengthy preoperative planning phase. This study assessed a specific type of navigation software, which is currently in use in maxillofacial surgery, to establish whether it might play a critical role in orthopaedic procedures. We report the case of a 43 year old female who sustained an isolated tibial plateau compression fracture (Schatzker IIIa), and who was successfully treated with open reduction and internal fixation, with the aid of intraoperative 3D imaging and new software navigation tools. This case demonstrates a combined approach using a new software tool based on intraoperative fluoroscopy-3D imaging. PMID- 20580887 TI - Leaf cuticular wax amount and crystal morphology regulate post-harvest water loss in mulberry (Morus species). AB - Mulberry leaves are the sole source of food for silkworms (Bombyx mori), and moisture content of the detached leaves fed to silkworms determines silkworm growth and cocoon yield. Since leaf dehydration in commercial sericulture is a serious problem, development of new methods that minimize post-harvest water loss are greatly needed. In the present study, variability in moisture retention capacity (MRC, measured as leaf relative water content after one to 5 h of air drying) was examined by screening 290 diverse mulberry accessions and the relationship between MRC and leaf surface (cuticular) wax amount was determined. Leaf MRC varied significantly among accessions, and was found to correlate strongly with leaf wax amount. Scanning electron microscopic analysis indicated that leaves having crystalline surface waxes of increased facet size and density were associated with high MRC accessions. Leaf MRC at 5 h after harvest was not related to other parameters such as specific leaf weight, and stomatal frequency and index. This study suggests that mulberry accessions having elevated leaf surface wax amount and crystal size and density exhibit reduced leaf post-harvest water loss, and could provide the foundation for selective breeding of improved cultivars. PMID- 20580888 TI - Evaluation of in vivo biological activities of tetrapyrrole ethanolamides as novel anticancer agents. AB - The tetrapyrrole ethanolamide derivatives, hematoporphyrin propylether ethanolamide (HPPEEA, 1) and pheophorbide a ethanolamide (PEA, 2) have previously shown some photodynamic activities in an in vitro photodynamic assay (D. Girard et al. Bioorg. Med. Chem. Lett. 18 (2008) 360-365). Extending this study to an in vivo one, HPPEEA and PEA were evaluated for their anticancer, toxicity, and pharmacokinetic activities in mouse animal models. The compounds showed moderate anticancer activity without apparent acute toxicity and without secondary tumour development. This indicates noteworthy anti-metastasis activity. The pharmacokinetic study revealed the compound fast clearances from body tissues. This is an important therapeutic concern since these compounds are light sensitive. Thus, the combination of photodynamic and anti-metastasis activities with fast tissue clearance indicates that HPPEEA and PEA are good candidates for further photodynamic treatment evaluations. PMID- 20580889 TI - Platelet function in dogs with congenital portosystemic shunt. AB - The aim of this study was to examine the influence of congenital portosystemic shunts (CPSS) on primary haemostasis in dogs. Bleeding time, automated platelet function analysis (PFA 100 analyser), platelet count and platelet aggregation using different methods and agonists were measured in 10 dogs with untreated CPSS and in 10 healthy, age-matched controls. Bleeding time, platelet function analysis and platelet counts did not differ significantly between groups (P>0.05). Aggregation measured using the impedance method (area under the curve) was slightly to moderately reduced with high concentrations of collagen (e.g., 5MUg/mL: 2948 +/- 524 vs. 3472 +/- 571 AU*Min) and arachidonic acid (e.g., 1mmol/L: 1006 +/- 522 vs. 1963 +/- 738 AU*Min) (P<0.05), but not with adenosine diphosphate. In contrast, collagen-induced turbidimetric aggregation revealed slightly higher maximum aggregation values in dogs with CPSS. Despite the moderately altered platelet aggregation, the lack of change in global primary haemostasis screening tests indicates that dogs with CPSS do not have regularly occurring clinically relevant disorders of primary haemostasis. PMID- 20580890 TI - Gene table: monogenic determined neurocutaneous disorders. AB - Neurocutaneous disorders are often associated with epilepsy, psychomotor development delay, and other neurological abnormalities. Recently, a great progress has been achieved in understanding the pathogenesis of many neurocutaneous disorders. This work presents very concise review of molecular background of monogenic determined neurocutaneous disorders. PMID- 20580891 TI - Adapted RF pulse design for SAR reduction in parallel excitation with experimental verification at 9.4T. AB - Parallel excitation holds strong promises to mitigate the impact of large transmit B(1) (B(1)(+)) distortion at very high magnetic field. Accelerated RF pulses, however, inherently tend to require larger values in RF peak power which may result in substantial increase in Specific Absorption Rate (SAR) in tissues, which is a constant concern for patient safety at very high field. In this study, we demonstrate adapted rate RF pulse design allowing for SAR reduction while preserving excitation target accuracy. Compared with other proposed implementations of adapted rate RF pulses, our approach is compatible with any k space trajectories, does not require an analytical expression of the gradient waveform and can be used for large flip angle excitation. We demonstrate our method with numerical simulations based on electromagnetic modeling and we include an experimental verification of transmit pattern accuracy on an 8 transmit channel 9.4T system. PMID- 20580892 TI - The effect of ultrasound on the gold plating of silica nanoparticles for use in composite solders. AB - In order to produce electronic devices that can survive harsh environments it is essential that the solder joints are very reliable and this has led to the development of composite solders. One approach to the manufacture of such solders is to disperse silica nanoparticles into it to improve their mechanical and fatigue characteristics. However, this is difficult to achieve using bare silica particles because they are not "wettable" in the solder matrix and so cannot be dispersed efficiently. In an attempt to alleviate this issue it has been found that if the silica nanoparticles are first plated with gold then this problem of wetting can, to some extent, be overcome. However, the particles must be completely encapsulated with gold which, using the method previously described by workers at Kings College London, was found to be difficult to accomplish. In this short communication the effect of ultrasound on the gold coverage is described. Different frequencies of ultrasound were used (20, 850 and 1176 kHz) and it was found that higher frequencies of ultrasound improved the coverage and dispersion of the gold nanoparticles over silica during the seeding step compared to simple mechanical agitation. This subsequently led to a more complete encapsulation of gold in the plating stage. PMID- 20580893 TI - A non-local approach for image super-resolution using intermodality priors. AB - Image enhancement is of great importance in medical imaging where image resolution remains a crucial point in many image analysis algorithms. In this paper, we investigate brain hallucination (Rousseau, 2008), or generating a high resolution brain image from an input low-resolution image, with the help of another high-resolution brain image. We propose an approach for image super resolution by using anatomical intermodality priors from a reference image. Contrary to interpolation techniques, in order to be able to recover fine details in images, the reconstruction process is based on a physical model of image acquisition. Another contribution to this inverse problem is a new regularization approach that uses an example-based framework integrating non-local similarity constraints to handle in a better way repetitive structures and texture. The effectiveness of our approach is demonstrated by experiments on realistic Brainweb Magnetic Resonance images and on clinical images from ADNI, generating automatically high-quality brain images from low-resolution input. PMID- 20580894 TI - Writing kinematics and pen forces in writer's cramp: effects of task and clinical subtype. AB - OBJECTIVE: Writer's Cramp (WC) is defined as a task-specific form of focal-hand dystonia generating hypertonic muscle co-contractions resulting in impaired handwriting. Little is known about kinematic and dynamic characteristics in handwriting in the different subtypes of WC. METHODS: In this study, kinematic and force analyses were used to compare handwriting capacity of 14 simple, 13 dystonic WC-patients and 14 healthy subjects. The effect of task-complexity was investigated using a simple repetitive writing-task, writing pairs of letters, a sentence and copying a text. RESULTS: In general, patients showed significant deficits in kinematic and force parameters during writing, but no consistent differences between the two subtypes of WC were found. The complexity of writing material modulated writing parameters in all groups, but less complex material did not ameliorate the patients' deficits relative to control subjects. CONCLUSIONS: The similarity of deficits in patients with simple and dystonic WC does not support the concept of a unitary progression of deficits causing a switch from simple to dystonic WC. Dystonic WC seems to be characterized by a spread of symptoms independent of severity. Obviously, the deficits concern elementary aspects of writing and are not modulated by more complex aspects. SIGNIFICANCE: Quantification of writing deficits by simple and short phrases with kinematic and force parameters can substantially improve the characterization of WC. PMID- 20580895 TI - What is dyslexia? Insights from electrophysiology. PMID- 20580896 TI - Best practices in the management of toxicities related to anti-EGFR agents for metastatic colorectal cancer. AB - PURPOSE: To provide oncology nurses with an overview of the toxicity management associated with the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab in patients with metastatic colorectal cancer. METHODS: Monoclonal antibodies such as cetuximab and panitumumab that target EGFR have provided patients with metastatic colorectal cancer with effective treatment options. Both antibodies can be used as monotherapy; cetuximab is also approved for use in combination with chemotherapy. We reviewed the literature regarding the signs and symptoms, assessment of severity, and strategies available to prevent and manage adverse events associated with these agents. KEY RESULTS: This class of therapeutics is associated with an overall acceptable adverse event profile that is distinctly different from conventional chemotherapeutics. In contrast to cytotoxic chemotherapy, which causes myelosuppression, mucositis, and nausea and vomiting, common toxicities reported for anti-EGFR therapy include the more frequent cutaneous toxicities, electrolyte imbalances, and diarrhoea, as well as the less frequent ocular toxicities. Infusion reactions are also observed with the chimerical monoclonal antibody cetuximab. CONCLUSIONS: Oncology nurses play a key role in the administration of multi-agent treatment regimens, especially with respect to the identification and management of toxicities, patient education, and patient support. By reducing the incidence and severity of the adverse events associated with anti-EGFR therapy, oncology nurses have the potential to sustain patient adherence to completion of treatment, identify signs and symptoms early, proactively manage adverse events, and provide appropriate treatment interventions, thereby improving patient quality of life. PMID- 20580897 TI - Assessment and management of nutritional challenges in children's cancer care: a survey of current practice in the United Kingdom. AB - BACKGROUND: The maintenance of an adequate nutritional intake is vital for the child or young person undergoing treatment for cancer. Inability to maintain nutrition can lead to poor tolerance of treatment, increased risk of infectious complications and a potential poorer overall outcome. Good nutritional support is vital however there does not appear to be a national or consistent approach to either nutritional support or assessment. PURPOSE: The Paediatric Oncology Nurses Forum of the Royal College of Nursing and the Paediatric Oncology Dieticians Interest Group surveyed practice in the 21 Children Cancer and Leukaemia Group Centres in the United Kingdom and Ireland with the express aim of reviewing current practice as a first stage towards developing national guidance for nutritional management. METHODS AND SAMPLE: Questionnaires designed to review nutritional assessment and nutritional interventions were distributed to both a nurse and dietician in each CCLG centre. The results were analysed using descriptive statistics. RESULTS: There was a 100% return rate from nurses and 66% from dieticians. The results showed an inconsistent approach in both assessment methods and approaches to nutritional intervention for this group of patients. CONCLUSION: It is recognised that there is a need to adequately assess and provide appropriate nutrition for children and young people receiving cancer therapies. This survey highlights the inconsistencies in practice today as well as the need for consistent and useful guidance especially in the area of nutritional assessment and management of potential malnutrition. PMID- 20580898 TI - Is bacterial vaginosis associated with a pro-inflammatory cytokine profile in endometrial secretions of women undergoing IVF? AB - The objective of this prospective cohort study was to elucidate whether bacterial vaginosis (BV) is associated with a pro-inflammatory endometrial secretion cytokine profile and whether there is a relationship between BV and the concentrations of a number of key regulatory cytokines, chemokines and growth factors. A total of 198 women undergoing IVF treatment were included. Prior to embryo transfer, participants underwent screening for BV according to Nugent criteria by a Gram-stained cervical smear. The concentrations of 17 soluble mediators of human implantation were measured by multiplex immunoassay in endometrial secretions aspirated prior to embryo transfer. Seventeen (8.6%) women had BV (Nugent score >6). Multivariable logistic regression showed a significant positive association between interleukin-beta and the presence of BV (P=0.011; Nugent score >6 versus 6) and a significant negative association between eotaxin and BV (P=0.003). No significant differences were found in the ratios of distinct pro- and anti-inflammatory cytokines in endometrial secretions from women with or without BV. In conclusion, BV is associated with higher concentrations of interleukin-beta in endometrial secretions compared with women without BV. However, no distinct difference in pro- and anti-inflammatory profiles is present. An effect on endometrial receptivity is unlikely. PMID- 20580899 TI - Increased HGF and c-Met in muscle tissues of polymyositis and dermatomyositis patients: beneficial roles of HGF in muscle regeneration. AB - We investigated the expression of hepatocyte growth factor (HGF), which has mitogenic and anti-fibrotic activities, in muscle tissue of polymyositis/dermatomyositis (PM/DM) patients, as well as its functional roles in cultured myoblasts. Immunohistochemistry in muscle from PM/DM patients revealed that HGF was expressed predominantly on infiltrating mononuclear cells and that muscle cells expressed the receptor c-met. Cultured myoblasts produced HGF; which was increased by IL-1alpha but suppressed by TGF-beta and dexamethasone. Exogenous HGF induced myoblast proliferation and reduced procollagen type I production. Furthermore, HGF enhanced the gene expression of muscle regulatory factors MyoD and Myf5, while suppressing expression of fibrosis-related genes, connective tissue growth factor and alpha-smooth muscle actin. Although dexamethasone showed contrasting effects to HGF on the expression of these genes, co-treatment with HGF ameliorated the effects of dexamethasone. Taking the beneficial roles of HGF into consideration, administration of HGF might contribute to muscle regeneration in PM/DM especially under corticosteroid treatment. PMID- 20580901 TI - Cumulative effect of vagus nerve stimulators on intractable seizures observed over a period of 3years. AB - OBJECTIVE: The objective of the study was to evaluate the efficacy of vagus nerve stimulator (VNS) therapy and identify factors associated with reduction of seizures. The VNS is an accepted therapeutic option for patients with refractory partial epilepsy. There are, however, limited data regarding efficacy in any specific group of patients with epilepsy. METHODS: This is a retrospective review of patients with epilepsy on VNS therapy initiated between January 2000 and December 2007 at a university medical center. Information collected included demographics, epilepsy type and duration, antiepileptic drug usage, stimulation parameters, and seizure frequency at baseline, 3months, 6months, 1year, 2years, and 3years after VNS therapy initiation. Seizure frequency at different follow-up intervals was compared with baseline frequency. Patients were stratified into three subsets based on VNS response. Relationships between VNS response and factors including demographics, location of seizure focus, type or duration of epilepsy, and VNS settings were examined as a whole as well as in subsets. RESULTS: Fifty-four patients were implanted with VNSs over a period of 7years. Four patients were excluded. A total of 50 patients (31 men, 19 women) with mean age 39years and on VNS therapy were included in this study. Average duration of VNS therapy was 4.5years. Baseline average frequency was 10 seizures per month. Significant decreases in median seizure frequency were noted at 3months (P<0.001), 6months (P<0.001), 1year (P=0.004), 2years (P<0.001), and 3years (P<0.0001). Seventy-two percent of the patients reported a decrease in seizure frequency within the first 3months, which increased to 80% by the end of 3years. Overall, the percentage reduction in seizure frequency was 64% at 3months and increased to 86% at the end of 3years. In the subset of patients who responded to VNSs, reduction in seizure frequency improved from 80 to 89% by the end of 3years. There were no correlations between seizure frequency and specific VNS settings, epileptic focus, or duration or type of epilepsy, in the group as a whole or in its subsets. Data suggest a favorable VNS response in patients with higher baseline seizure frequency. CONCLUSIONS: Significant reductions in seizure frequency were noted with VNS therapy over a 3-year follow-up period with a possible cumulative effect. Lateralization or localization of epileptic focus or epilepsy subtype did not correlate with response to VNSs. PMID- 20580900 TI - Cortical gamma-oscillations modulated by visuomotor tasks: Intracranial recording in patients with epilepsy. AB - We determined how visuomotor tasks modulated gamma-oscillations on electrocorticography in epileptic patients who underwent epilepsy surgery. Each visual-cue consisted of either a sentence or hand gesture instructing the subject to press or not to press the button. Regardless of the recorded hemisphere, viewing sentence and gesture cues elicited gamma-augmentation sequentially in the lateral-polar occipital and inferior occipital-temporal areas; subsequently, button-press movement elicited gamma-augmentation in the Rolandic area. The magnitudes of gamma-augmentation in the Rolandic and inferior occipital-temporal areas were larger when the hand contralateral to the recorded hemisphere was used for motor responses. A double dissociation was found in the left inferior occipital-temporal cortex in one subject; the lateral portion had greater gamma augmentation elicited by a sentence-cue, whereas the medial portion had greater gamma-augmentation elicited by a gesture-cue. The present study has increased our understanding of the physiology of the human visuomotor system. PMID- 20580902 TI - Laparoscopic ureteroureteral anastomosis for distal ureteral injuries during gynecologic laparoscopic surgery. AB - STUDY OBJECTIVE: To estimate the feasibility and surgical outcomes of laparoscopic ureteroureteral for treatment of distal ureteral injuries. DESIGN: Retrospective clinical study (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Four women with ureteral transection or ureterovaginal fistula. INTERVENTION: Laparoscopic ureteroureteral . MEASUREMENTS AND MAIN RESULTS: Median age of patients was 44 (range, 33-63) years, and median operating time was 110 (range, 85-150) minutes. There were no conversions to laparotomy. No intraoperative or postoperative complications occurred. Follow-up ranged from 20 to 46 months. All patients have been asymptomatic, and follow-up intravenous pyelograms and ultrasound examinations have been normal. CONCLUSION: Laparoscopic ureteroureteral anastomosis is an alternative surgical option in women with distal ureteral injuries during gynecologic laparoscopic surgery. PMID- 20580903 TI - Effect of Mg ions on efficiency of gene electrotransfer and on cell electropermeabilization. AB - Gene electrotransfer is a promising nonviral method that enables DNA to be transferred into living cells with electric pulses. However, there are many parameters that determine gene electrotransfer efficiency. One of the steps involved in gene electrotransfer is interaction of DNA with the cell membrane. Divalent cations in the electroporative media can influence the anchoring of DNA to the cell membrane and by that gene electrotransfer efficiency. Here we report the effect of different concentrations of Mg2+ on electropermeabilization for small molecule (propidium iodide), gene electrotransfer and viability of the cells. We also used TOTO-1 dye to visualize DNA-cell membrane interaction for different [Mg]. For this purpose, we used different electroporative media with increasing [Mg]. Our study shows that higher [Mg] lead to higher electropermeabilization for propidium iodide and higher viability, while causing lower gene electrotransfer efficiency. Because we observed higher TOTO-1 labeled DNA at cell surface when using higher [Mg], we suggest that Mg2+ ions can bind DNA at cell surface at such strength that cannot pass into the cell during application of electric pulses, which can lead to lower gene transfection. There may also be other mechanisms involved, since there are many steps of gene electrotransfer on which Mg2+ ions can have an effect on. Our results also imply that membrane permeability changes are not sufficient for an efficient gene electrotransfer. PMID- 20580904 TI - Increasing water temperature and disease risks in aquatic systems: climate change increases the risk of some, but not all, diseases. AB - Global warming may impose severe risks for aquatic animal health if increasing water temperature leads to an increase in the incidence of parasitic diseases. Essentially, this could take place through a temperature-driven effect on the epidemiology of the disease. For example, higher temperature may boost the rate of disease spread through positive effects on parasite fitness in a weakened host. Increased temperature may also lengthen the transmission season leading to higher total prevalence of infection and more widespread epidemics. However, to date, general understanding of these relationships is limited due to scarcity of long-term empirical data. Here, we present one of the first long-term multi pathogen data sets on the occurrence of pathogenic bacterial and parasitic infections in relation to increasing temperatures in aquatic systems. We analyse a time-series of disease dynamics on two fish farms in northern Finland from 1986 to 2006. We first demonstrate that the annual mean water temperature increased significantly on both farms over the study period and that the increase was most pronounced in the late summer (July-September). Second, we show that the prevalence of infection (i.e. proportion of fish tanks infected each year) increased with temperature. Interestingly, this pattern was observed in some of the diseases (Ichthyophthirius multifiliis, Flavobacterium columnare), whereas in the other diseases, the pattern was the opposite (Ichthyobodo necator) or absent (Chilodonella spp.). These results demonstrate the effect of increasing water temperature on aquatic disease dynamics, but also emphasise the importance of the biology of each disease, as well as the role of local conditions, in determining the direction and magnitude of these effects. PMID- 20580905 TI - Polyparasitism and its impact on the immune system. AB - Parasitic infections are common in many tropical and sub-tropical regions of the world and concomitant infection, polyparasitism, is the rule rather than the exception in such areas. At the immunological level, different parasites induce quite different responses characterised, for example, by protozoa that polarise responses towards Th1, whilst helminths are strong Th2 and regulatory T cell inducers. The question of how the co-existence of such parasites within the same host might influence the immunological responses to each species and, more importantly, whether such interactions affect resistance, susceptibility or clinical outcome, needs to be addressed in well-designed studies of sufficient power. The current paper discusses what we know as well as the gaps in our knowledge of polyparasitism. PMID- 20580906 TI - Cardiac computed tomography for prediction of myocardial viability after reperfused acute myocardial infarction. AB - BACKGROUND: Perfusion defects (PDs) detected with cardiac magnetic resonance (CMR) imaging predict the functional recovery of myocardial function after acute myocardial infarction. OBJECTIVE: We evaluated the ability of cardiac computed tomography (CCT) to predict the recovery of regional left ventricular (LV) systolic function after ST elevation myocardial infarction (STEMI). METHODS: Seventeen patients (mean age, 60610 years) presenting with STEMI were prospectively studied. Each patient underwent CCT and CMR at baseline and after an average of 6 months. Areas of PD were quantified. Segmental LV systolic function was semiquantitatively assessed by CMR. An improvement at 6 months by R1 category in the regional wall motion score was considered LV recovery. RESULTS: Coronary artery revascularization was successfully performed with post procedural TIMI 3 flow in 16 cases. On CCT assessment, 107 of 289 segments (37%) had some degree of PD. On follow-up, segments with,25%PD at baseline had no worsening of wall motion. In segments with.75%PD, 89% (9 of 11) showed akinesis or worsening of wall motion. The odds ratio for improvement in segmental wall motion with increasing PD category was 0.63 (95% CI, 0.42-0.97; P 5 0.035). The degree of PD on CT predicted LV recovery at follow-up (P , 0.0001). CONCLUSIONS: The transmural extent of myocardial infarction as detected and quantified with CCT predicts the recovery of regional systolic LV function after revascularization for acute STEMI. PMID- 20580908 TI - Inhibitory influence of mecamylamine on the development and the expression of ethanol-induced locomotor sensitization in mice. AB - Several evidences have indicated the involvement of neuronal nicotinic acetylcholine receptors (nAChR) in behavioral effects of drugs of abuse, including ethanol. nAChRs are implicated in ethanol-induced behaviors as well as neurochemical responses to ethanol. Recently, it is demonstrated that mecamylamine, a nAChR antagonist blocks cocaine-, d-amphetamine-, ephedrine-, nicotine-, and methylphenidate-induced psychomotor sensitization. However, no reports are available on its role in ethanol-induced psychomotor sensitization. Therefore, an attempt was made to evaluate its effect on ethanol-induced locomotor sensitization using a model previously described by us. The results revealed that acute administration of mecamylamine (1 and 2mg/kg, i.p.) blocked the acute stimulant effect of ethanol (2.0g/kg, i.p.). In addition, treatment with mecamylamine (0.5-2.0mg/kg, i.p.), 30min prior to the challenge dose of ethanol (2.0g/kg, i.p.) dose dependently attenuated expression of sensitization to locomotor stimulant effect of ethanol. Moreover, administration of mecamylamine (1 and 2mg/kg, i.p.) during development (prior to each ethanol injection on days 1, 4, 7, and 10) blocked acquisition as well as expression (day 15) of sensitization to locomotor stimulant effect of ethanol. Mecamylamine per se did not affect locomotor activity. Further, it also did not influence blood ethanol levels and rotarod performance in mice. These results support the hypothesis that neuroadaptive changes in nAChRs may participate in the development and the expression of ethanol-induced locomotor sensitization. PMID- 20580909 TI - Tramadol acts as a weak reinforcer in the rat self-administration model, consistent with its low abuse liability in humans. AB - Rodent models of abuse potential are considered to represent a false positive with respect to the low risk of abuse liability associated with the atypical opioid analgesic tramadol. This may reflect either the predictive limitations of the models used to formulate this proposition (drug discrimination and conditioned place preference) or the predictive ability of the rodent per se. To address this concern, we used the rat self-administration model to examine the reinforcing properties of tramadol (0.3-3mg/kg/infusion) under fixed (FR) and progressive-ratio (PR) schedules of reinforcement. Comparisons were made with the typical opioid analgesics morphine (0.03-0.3mg/kg/infusion) and remifentanil (0.001-0.03mg/kg/infusion). All three compounds maintained responding under an FR3 schedule of reinforcement, although clear differences were observed in the rates of responding between compounds. Under a PR schedule, morphine and remifentanil maintained comparable break points, while break points for tramadol did not differ from vehicle. Thus, when examined in the self-administration model, tramadol acts as a relatively weak reinforcer in rodents. These data are consistent with the low risk of tramadol abuse liability in humans and highlight the value of using multiple abuse potential models for assessing abuse liability. PMID- 20580910 TI - An improved shuttle vector constructed for metabolic engineering research in Corynebacterium glutamicum. AB - Corynebacterium glutamicum is an industrial microorganism for production of amino acids. However, the metabolic engineering in C. glutamicum has been retarded due to lack of suitable vectors. In this study, we have constructed a shuttle vector pDXW-10 which harbors a large multiple cloning site suitable for cloning multiple genes, and a tac-M promoter suitable for constitutive gene expression in C. glutamicum. The cat gene was subcloned into the vector and the expression levels of the CAT protein were found different in Escherichia coli and C. glutamicum; high-level in the former but moderate-level in the latter. The pDXW-10 would be an ideal vector for research on metabolic engineering in C. glutamicum. PMID- 20580907 TI - Vision and driving. AB - Driving is the primary means of personal travel in many countries and relies heavily on vision for its successful execution. Research over the past few decades has addressed the role of vision in driver safety (motor vehicle collision involvement) and in driver performance (both on-road and using interactive simulators in the laboratory). Here we critically review what is currently known about the role of various aspects of visual function in driving. We also discuss translational research issues on vision screening for licensure and re-licensure and rehabilitation of visually impaired persons who want to drive. PMID- 20580911 TI - Alpha-synuclein, lipids and Parkinson's disease. AB - Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease, among the aging human population. The main symptoms of Parkinson's disease such as tremor and movement disabilities are the result of degeneration of dopaminergic neurons in substantia nigra pars compacta. The widely-accepted subcellular factor which underlies Parkinson's disease neuropathology is the presence of Lewy bodies with characteristic inclusions of aggregated alpha-synuclein. This small soluble protein has been implicated in a range of interactions with phospholipid membranes and free fatty acids. The precise biological function of this protein is, however, still under investigation. Here we review the evidence linking alpha-synuclein, lipid metabolism, fatty acid oxidation, mitochondrial damage and Parkinson's disease. We propose that association of alpha-synuclein with oxidized lipid metabolites can lead to mitochondrial dysfunction in turn leading to dopaminergic neuron death and thus to Parkinson's disease. PMID- 20580912 TI - Identification of an atypical peptidyl-prolyl cis/trans isomerase from trypanosomatids. AB - The parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases) catalyzes the cis/trans isomerization of the peptide bonds preceding Pro residues. Eukaryotic parvulin-type PPIases have been shown to be involved in cell proliferation and cell cycle progression. Here we present the biochemical and molecular characterization of a novel multi-domain parvulin-type PPIase from the human pathogenic Trypanosoma cruzi, annotated as TcPar45. Like most other parvulins, Par45 has an N-terminal extension, but, in contrast to human Pin1, it contains a forkhead-associated domain (FHA) instead of a WW domain at the N terminal end. Par45 shows a strong preference for a substrate with the basic Arg residue preceding Pro (Suc-Ala-Arg-Pro-Phe-NH-Np: k(cat)/K(M)=97.1 /M/s), like that found for human Par14. In contrast to human Pin1, but similarly to Par14, Par45 does not accelerate the cis/trans interconversion of acidic substrates containing Glu-Pro bonds. It is preferentially located in the parasite nucleus. Single RNA interference (RNAi)-mediated knock-down showed that there was a growth inhibition in procyclic Trypanosoma brucei cells. These results identify Par45 as a phosphorylation-independent parvulin required for normal cell proliferation in a unicellular eukaryotic cell. PMID- 20580913 TI - A novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery. AB - Ursodeoxycholic acid (UA) modified protein-lipid nanocomplex (uP-LNC) as a novel biomimetic nanocarrier was developed for tumor-targeting delivery. Bovine serum albumin (BSA) was used as a model protein and its amino groups were covalently modified by UA. Lipid nanoparticle (LNP) composed of phospholipids, triglycerides and octadecylamine was prepared by using solvent evaporation method and was used as the core. UA modified BSA (uP) was attached onto the surface of LNP by post insert method and generated the protein-lipid nanocomplex. As the control, cholesteryl hemiglutarate (CH), a non-targeting ligand was also used to modify BSA and then formed CH modified protein-lipid nanocomplex (cP-LNC). The combining efficiency of modified BSA with LNP, determined by Bradford protein assay, increased with the enhancement of substitution degree. The modified BSA and nanocomplex were characterized for the substitute degree, average molecular weight, surface tension, particle size and zeta potential by various physicochemical analyses. In vitro dissolution tests and cell uptake studies were performed by loading coumarin-6 as a fluorescent probe. The results indicated that the UA modified protein attached on the nanoparticles significantly decreased drug release from the nanocomplex in pH 7.4 medium, The uptake of uP LNC was higher in hepatic carcinoma cells (HepG2 and Bel 7402) than in normal liver cells (L02). Furthermore, the uptake of uP-LNC was significantly higher than that of cP-LNC and LNP in these cells. The uptake was dependent on time, temperature and concentration, and could be inhibited by free UA. In addition, the MTT assay of uP-LNC and u(x)P with various degrees of substitution showed very low cytotoxicity at tested concentrations in all cells. The UA modification served to facilitate the specific receptor and energy mediated endocytosis process of the protein-lipid nanocomplex and enabled this nanocomplex to be a potential nanocarrier for tumor-targeting drug delivery. PMID- 20580914 TI - Improvement of the monitoring and biosafety of encapsulated cells using the SFGNESTGL triple reporter system. AB - Cell microencapsulation may represent a breakthrough to overcome problems associated with cell therapy. Advances in material biocompatibility and production protocols have put this field close to its clinical application. However, issues such as the possibility of tracking cell-containing microcapsules, monitoring cell viability, and discontinuation of the therapeutic activity when necessary, still remain unsolved. We demonstrate here simultaneous monitoring and pharmacological control of myoblasts-containing alginate microcapsules, injected in immunocompetent mice after transduction with the SFG(NES)TGL triple reporter retroviral vector, which contains green fluorescence protein (GFP), firefly luciferase and herpes simplex virus type 1 thymidine kinase (HSV1-TK). Naked (as controls) or microencapsulated cells were subcutaneously injected in C57BL/6J mice and followed up by luminometry. Signal for naked cells disappeared 2 weeks after cell injection, whereas signal for microencapsulated cells remained strong for 8 months, thus demonstrating the presence of living cells. Treatment of mice with the thymidine-kinase substrate ganciclovir caused death of microencapsulated myoblasts, as seen by a drastic decay in the light emission and histological analysis. Hence, we conclude that incorporation of the SFG(NES)TGL vector into microencapsulated cells represents an accurate tool for controlling cell location and viability in a non-invasive way. Moreover, cell death can be induced by administration of ganciclovir, in case therapy needs to be interrupted. This system may represent a step forward in the control and biosafety of cell- and gene- therapy-based microencapsulation protocols. PMID- 20580915 TI - The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. AB - It has been reported that nanoparticles (NPs) prepared by hydrophobically modified polymers could accumulate passively in the tumor tissue; however, their cellular uptake mechanism and intercellular trafficking pathway have never been understood. This study was designed to address these concerns, using NPs prepared by a hydrophobically-modified chitosan (N-palmitoyl chitosan, NPCS). Molecular dynamic simulations found that a degree of substitution (DS) of 5% of palmitoyl groups on its backbone was sufficient to allow NPCS to form NPs, due to a significant increase in the intra- and intermolecular hydrophobic interactions. With an increase of DS, there were more palmitoyl groups present on the surface of NPs which were then able to interact with the cell membranes. A greater extent of cellular uptake of NPCS NPs was observed with increasing the DS on NPCS. The internalization of NPCS NPs was clearly related with the lipid raft-mediated routes; with increasing the DS on NPCS, the caveolae-mediated endocytosis became more important. The results obtained in the intracellular trafficking study showed that NPCS NPs entered cells via caveolae and transiently localized to caveosomes before trafficking to the endosomal pathway. These results suggest that the prepared NCPS NPs may serve as a carrier for intracellular delivery of therapeutic agents. PMID- 20580916 TI - Chronobiological aspects of nutrition, metabolic syndrome and obesity. AB - The present review starts from the classical physiological and nutritional studies related with food intake control, digestion, transport and absorption of nutrients. It continues with studies related with the metabolism of adipose tissue, and finish with modern experiments in genetics and molecular biology - all from a fresh, chronobiological point of view. Obesity will be explained as a fault in the circadian system, as pathology associated with "chronodisruption". The main gaps in chronobiological research related to obesity will be also identified and chronobiological-based therapies will be proposed in order to allow the resetting of the circadian rhythm among obese subjects. PMID- 20580917 TI - Twenty-eight days repeated oral dose toxicity study of gemifloxacin in Wistar albino rats. AB - The purpose of this study was to investigate the potential toxicity of gemifloxacin by 28-day repeated oral dose in Wistar albino rats. The test article, was administered daily by gavage to male and female rats at dose levels of 0, 50, 100, 200 mg/kg/day. At the end of treatment period, 12 rats/sex/group was sacrificed, while six extra rats/sex in the vehicle control and highest dose groups sacrificed after 14 days recovery period. During the treatment and recovery periods, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, phototoxicity, hematology, serum biochemistry, synovial fluid biochemistry, electrocardiogram (ECG), gross findings, organ weights, microscopic examination of synovial fluid, and histopathology were examined. Hematological and serum biochemical investigations revealed a dose-dependent increase in the total white blood cell (WBC), total bilirubin (T-BIL), glucose (GLU), alanine aminotransferase (ALT) and significant decreases in total protein (TP) were observed in both sexes at the same dose, at the end of treatment period, but the levels returned toward normal during the recovery period. Histopathology of talar joint showed that erosion of the articular surface of that joint in both sexes at the end of treatment period at the dose level of 200 mg/kg/day. Degenerative changes in tendinocytes were observed in Achilles tendon of both sexes at the high dose level at the end of treatment period. In histopathological study shows partial effacement of liver architecture and focal ulceration in gastric mucosa at the high dose level at the end of treatment period. Based on these results, it was concluded that 28 days repeated oral dose of gemifloxacin caused increases in the liver weight, WBC count, T-BIL, glucose level, ALT, decreasing the TP, cause chronic hepatitis and acute gastritis, erosion of the articular surface of joint and histopathologic changes in Achilles tendon in rats at the dose level of 200 mg/kg/day. PMID- 20580918 TI - Can -omics inform a food safety assessment? AB - Omic technologies can in principle allow visualization of the all of changes that take place when the genetics, nutrition or environment of an organism is altered. Targeted compositional analysis is today a key component of the food safety assessment paradigm in which known nutrients, anti-nutrients, toxicants, allergens, and other molecules of potential biological importance to humans or animals are quantitatively analyzed. This allows safety assessors to compare the composition and safety of one food with closely related counterparts. Omic technologies measure many analytes-some of which are unidentified-but the analysis often sacrifices one or more of the characteristics of validated analytical methods currently used for food analysis. Databases that would allow the safety assessor to interpret differences are not currently available. There is also no reason to believe that the targeted compositional analysis in use today does not provide the evidence needed to ensure food safety, nor is there any current reason to believe that omics can add value to the safety assessment process. The regulation of transgenic crops is far more rigorous than is justified since they present no new risks compared with traditional breeding, and are more precisely defined and better understood than their non-transgenic equivalent. PMID- 20580919 TI - Early-life stress and antidepressants modulate peripheral biomarkers in a gene environment rat model of depression. AB - BACKGROUND: Availability of peripheral biomarkers for depression could aid diagnosis and help to predict treatment response. The objective of this work was to analyse the peripheral biomarker response in a gene-environment interaction model of depression. Genetically selected Flinders Sensitive Line (FSL) rats were subjected to maternal separation (MS), since early-life trauma is an important antecedent of depression. An open-ended approach based on a proteomic analysis of serum was combined with the evaluation of depression-associated proteins. METHODS: Rats experienced MS and chronically received escitalopram (ESC) or nortryptiline (NOR). Serum proteins were compared by two-dimensional gel electrophoresis. Corticosterone, cytokines, BDNF and C-reactive protein (CRP) were measured by immunoassays. RESULTS: Comparing FSL with the control Flinders Resistant Line (FRL), Apo-AI and Apo-AIV, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were significantly modulated. Significant increases were detected in leptin, interleukin (IL) 1alpha and BDNF. CRP levels were significantly reduced. The impact of early-life stress was assessed by comparing FSL+MS versus FSL. Apo-E, alpha1-macroglobulin, complement-C3, transferrin and hemopexin were significantly modulated. The effect of stress in antidepressant response was then evaluated. In the comparison FSL+ESC+MS versus FSL+ESC, albumin, alpha1-macroglobulin, glutathione peroxidase and complement-C3 were modulated and significant reductions were detected in IL4, IL6, IL10, CRP and BDNF. By comparing FSL+NOR+MS versus FSL+NOR proteins like Apo-AIV, pyruvate dehydrogenase, alpha1-macroglobulin, transferrin and complement-C3 showed different levels. CONCLUSIONS: Lipid metabolism and immunity proteins were differently expressed in FSL in comparison with FRL. Exposure to MS induced changes in inflammation and transport proteins which became apparent in response to antidepressant treatments. Modulated proteins could suggest biomarker studies in humans. PMID- 20580920 TI - Prefrontal brain metabolites in short-term weight-recovered adolescent anorexia nervosa patients. AB - Various neuroimaging techniques have revealed morphological and functional alterations in anorexia nervosa (AN), although few spectroscopic magnetic resonance studies have examined short-term weight-recovered AN patients. Subjects were 32 female adolescent patients (between 13 and 18 years old) seen consecutively in our department and who met DSM-IV diagnostic criteria for AN. All of them had received a minimum of six months of treatment and were short-term weight-recovered (for one to three months) with a body mass index ranging from 18 to 23. A group of 20 healthy female volunteer controls of similar age were also included. All subjects were assessed with psychopathological scales and magnetic resonance spectroscopy. Total choline (Cho) (p=0.007) and creatine (Cr) (p=0.008) levels were significantly higher in AN patients than in controls. AN patients receiving psychopharmacological treatment with SSRIs (N=9) had metabolite levels similar to control subjects, but patients without this treatment did not. The present study shows abnormalities in brain neurometabolites related to Cho compounds and Cr in the prefrontal cortex in short-term weight-recovered adolescent AN patients, principally in patients not undergoing psychopharmacological treatment. More studies with larger samples are necessary to test the generalizability of the present results. PMID- 20580921 TI - Relationship between polysialylated neural cell adhesion molecule and beta endorphin- or gonadotropin releasing hormone-containing neurons during activation of the gonadotrope axis in short daylength in the ewe. AB - Morphological plasticity has been demonstrated between breeding and anestrous seasons in the ewe hypothalamus, particularly for the gonadotropin-releasing hormone (GnRH) system. We sought to determine the impact of a photoperiodic transition, from long days (LD, 16 h light/24 h) to short days (SD; 8 h light/24 h), on the association between a marker of cerebral plasticity, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), and two diencephalic populations: the GnRH and beta-endorphin (beta-END) neurons, the latter being potent inhibitors of GnRH neuronal activity. We also estimated the number of contacts on GnRH neurons after the passage to SD, using synaptophysin as a marker for synaptic buttons. Those parameters were evaluated in ovariectomized estradiol-replaced ewes using double immunocytochemistry and confocal microscopy at different times after the transition to SD: day 0 (D0), D30, D45, D60 and D112. Luteinizing hormone (LH) secretion was recorded throughout the experiment. High LH levels were observed only at D112. Significantly more PSA-NCAM was found in the GnRH neuron perimeters in the D112 group than in the other groups. This increase was not associated with any change in the number of synaptophysin-immunoreactive contacts on GnRH neurons. The beta END peri-neuronal space was affected negatively by the transition to SD: the percentage of PSA-NCAM on beta-END neurons decreased between D45 and D112 in the posterior two thirds of the arcuate nucleus (ARC). These results suggest that photoperiod may reorganize cell interactions in different hypothalamic areas, ultimately reactivating GnRH neurons, in our model of ovariectomized-estradiol replaced ewes. PMID- 20580923 TI - New withanolides from Mandragora officinarum: first report of withanolides from the Genus Mandragora. AB - Two new withanolides named mandragorolide A (1) and mandragorolide B (2) were isolated from the MeOH extract of the whole plant of Mandragora officinarum of Jordanian origin, along with five known withanolides namely larnaxolide A (3), withanolide B (4), datura lactone 2 (5), withanicandrin (6) and salpichrolide C (7). Compound 3 has been reported only once before, from the leaves of Larnax glabra. This is the first report of withanolides of different biogenetic types from the genus Mandragora. Isolation of known fatty compounds, coumarins, sterols and tropane alkaloids was also achieved in this study. PMID- 20580922 TI - New coumarin glycosides from the leaves of Diospyros crassiflora (Hiern). AB - Two new 5-methylcoumarin glycosides named diosfeboside A (1) and B (2) and five known compounds namely kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 -> 2)-beta-D glucopyranoside (3), ursolic acid (4), betulinic acid (5), stigmasterol (6) and stigmasterol 3-O-beta-D-glucopyranoside (7) were isolated from the leaves of Diospyros crassiflora (Hiern). Their structures were established through interpretation of 1 and 2D NMR, mass spectra analysis and comparison with reported data. In vitro cytotoxic activity of the new compounds against human carcinoma cell lines (HL-60, Bel-7402, BGC-823, and KB) was evaluated and no cytotoxicity was observed for each of them. PMID- 20580924 TI - New norlignan derivatives from Curculigo capitulata. AB - Two new norlignan derivatives, crassifoside I (1) and sinensigenin C (2), were isolated from the rhizomes of Curculigo capitulate, along with six known norlignan derivatives, 1,1-bis(3,4-dihydroxyphenyl)-1-(2-furan)-methane (3), crassifogenin B (4), crassifoside A (5), breviscaside A (6), crassifoside D (7), and curcapital (8). Their structures were elucidated on the basis of spectral evidence and comparisons with literature data. The 1H and 13C NMR data of compound 3 was first assigned. Compounds 3-7 were isolated from this plant for the first time. PMID- 20580925 TI - Behavioral and genetic investigations of low exploratory behavior in Il18r1(-/-) mice: we can't always blame it on the targeted gene. AB - The development of gene-targeting technologies has enabled research with immune system-related knockout mouse strains to advance our understanding of how cytokines and their receptors interact and influence a number of body systems, including the central nervous system (CNS). A critical issue when we are interpreting phenotypic data from these knockout strains is the potential role of genes other than the targeted one. Although many of the knockout strains have been made congenic on a C57BL/6 (B6) genetic background, there remains a certain amount of genetic material from the129 substrain that was used in the development of these strains. This genetic material could result in phenotypes incorrectly attributed to the targeted gene. We recently reported low-activity behavior in Il10(-/-) mice that was linked to this genetic material rather than the targeted gene itself. In the current study we confirm the generalizability of those earlier findings, by assessing behavior in Il18(-/-) and Il18r1(-/-) knockout mice. We identified low activity and high anxiety-like behaviors in Il18r1(-/-) mice, whereas Il18(-/-) mice displayed little anxiety-like behavior. Although Il18r1(-/-) mice are considered a congenic strain, we have identified substantial regions of 129P2-derived genetic material not only flanking the ablated Il18r1 on Chromosome 1, but also on Chromosomes 4, 5, 8, 10, and 14. Our studies suggest that residual 129-derived gene(s), rather than the targeted Il18r1 gene, is/are responsible for the low level of activity seen in the Il18r1(-/-) mice. Mapping studies are necessary to identify the gene or genes contributing to the low activity phenotype. PMID- 20580927 TI - Erythropoietin and sonic hedgehog mediate the neuroprotective effects of brain derived neurotrophic factor against mitochondrial inhibition. AB - Brain-derived neurotrophic factor (BDNF) deficiency and mitochondrial dysfunction have been implicated in the pathogenesis of Huntington's disease (HD). 3 Nitropropionic acid (3-NP) is a mitochondrial inhibitor commonly used as a pharmacological model mimicking HD. We have recently reported that preconditioning of primary rat cortical cultures with BDNF induces sonic hedgehog (SHH), which contributes to the protective effects of BDNF against 3-NP neurotoxicity. Because carbamylated erythropoietin (EPO) may induce SHH, we investigated whether BDNF-dependent SHH expression and 3-NP resistance require prior induction of EPO. We found that BDNF induced EPO expression at both mRNA and protein levels. BDNF-mediated SHH induction and 3-NP resistance were abolished by the soluble EPO receptor (sEPO-R), an EPO inhibitor. Recombinant rat EPO (rEPO) induced SHH and attenuated 3-NP neurotoxicity. The rEPO-dependent neuroprotection was suppressed by the SHH inhibitor cyclopamine (CPM); however, sEPO-R failed to affect SHH neuroprotection. Furthermore, the rEPO-dependent neuroprotection was not suppressed by the BDNF neutralizing antibody, which completely abolished BDNF-mediated 3-NP resistance at the same dosage. Overall, our results demonstrate that BDNF-dependent SHH expression and 3-NP resistance require prior induction of EPO, thus establishing a signaling cascade of "BDNF- >EPO-->SHH-->3-NP resistance" in rat cortical neurons. PMID- 20580926 TI - Dendritic cells are early responders to retinal injury. AB - The presence and activity of dendritic cells (DC) in retina is controversial, as these cells are difficult to identify in retina due to limited markers and sparse numbers. Transgenic mice that express green fluorescent protein (GFP) on the CD11c promoter to label DC allowed the visualization and quantification of retinal DC. Two retina injury models, the optic nerve crush (ONC) and light injury, were used to study their injury response. Many GFP(+) DC were tightly associated with retinal ganglion cell nerve fibers following ONC, while very few microglia (GFP(-)CD11b(+) cells) were found in close contact. The GFP(+) cells were greatly elevated in the outer plexiform layer following photic injury. All of the GFP(+) DC were CD11b(+), suggesting a myeloid origin. In addition, the GFP(+) DC upregulated expression of MHC class II after injury, while the GFP( )CD11b(+) microglia did not. This study shows that DC were found in the retina and that they rapidly responded to neural injuries. We propose that they are a previously overlooked population, distinct from microglia, and may be important in the injury response. PMID- 20580928 TI - NADPH oxidase Nox1 contributes to ischemic injury in experimental stroke in mice. AB - Reactive oxygen species (ROS) are mediators of brain injury in ischemia/reperfusion. An involvement of the NADPH oxidase Nox2 has been demonstrated. In contrast, only little is known about the contribution of the Nox1 homologue in this context. Thus, we studied the role of Nox1 in early cerebral reperfusion injury in the middle cerebral artery filament occlusion model using Nox1 knockout mice. Genetic deletion of a functional Nox1 lead to a 55% attenuation in lesion size at 24h after induction of 1h ischemia (p<0.05). This result was paralleled by a significant improvement of neurological outcome, preservation of blood-brain barrier integrity and reduced cerebral edema in Nox1(y/)(-) compared to WT mice. Interestingly, no difference in infarct size between WT and Nox1(y/)(-) was observed with an occlusion time of 2h and longer. Apoptosis rate as measured by TUNEL staining was similar between the groups. Moreover, infusion of the antioxidant TEMPOL as well as of the unspecific NO synthase inhibitor l-NAME elicited similar changes with respect to ischemic tissue damage between WT and Nox1-deficient mice. In conclusion, Nox1 is involved in the pathophysiology of cerebral ischemia. Our data however indicate that ROS mediated direct cellular injury is unlikely to explain the protective effect achieved by genetic deletion of the enzyme. PMID- 20580929 TI - Alcohol-induced neuroapoptosis in the fetal macaque brain. AB - The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fascicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8h, then the fetuses were delivered by caesarean section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD. PMID- 20580930 TI - The bridge-region of the Ku superfamily is an atypical zinc ribbon domain. AB - Members of the Ku superfamily are DNA-end-binding proteins involved in non homologous end-joining (NHEJ) DNA repair. The published crystal structure of human Ku-DNA complex reveals a heterodimer that forms a ring around dsDNA by means of the Ku core modules. These modules contain a highly conserved seven stranded beta-barrel, which in turn contains an insertion, termed the bridge region, between its second and third beta-strands. The bridge-region adopts an unusual beta-strand-rich structure critical for dsDNA-binding and Ku function, but its provenance remains unclear. Here, we demonstrate that the bridge-region of Ku is a novel member of the diverse Zn-ribbon fold group. Sequence analysis reveals that Ku from several Gram-positive bacteria and bacteriophages retain metal-chelating motifs, whereas they have been lost in the versions from most other organisms. Structural comparisons suggest that the Zn-ribbon from Ku-bridge region is the first example of a circularly permuted, segment-swapped Zn-ribbon. This finding helps explain how Ku is likely to bind DNA as an obligate dimer. Further, we hypothesize that retention of the unusual conformation of the turns of the Zn-ribbons, despite loss of the Zn-binding sites, provides clues regarding the mechanism by which the Ku-bridge-regions sense the DNA state. PMID- 20580931 TI - Experimental modeling of explosive blast-related traumatic brain injuries. AB - This study aims to characterize the interaction of explosive blast waves through simulated anatomical systems. We have developed physical models and a systematic approach for testing traumatic brain injury (TBI) mechanisms and occurrences. A simplified series of models consisting of spherical poly(methyl methacrylate) (PMMA) shells housing synthetic gelatins as brain simulants have been utilized. A series of experiments was conducted to compare the sensitivity of the system response to mechanical properties of the simulants under high strain-rate explosive blasts. Small explosive charges were directed at the models to produce a realistic blast wave in a scaled laboratory setting. Blast profiles were measured and analyzed to compare system response severity. High-speed shadowgraph imaging captured blast wave interaction with the head model while particle tracking captured internal response for displacement and strain correlation. The results suggest amplification of shock waves inside the head near material interfaces due to impedance mismatches. In addition, significant relative displacement was observed between the interacting materials suggesting large strain values of nearly 5%. Further quantitative results were obtained through shadowgraph imaging of the blasts confirming a separation of time scales between blast interaction and bulk movement. These results lead to a conclusion that primary blast effects may potentially contribute significantly to the occurrence of military associated TBI. PMID- 20580932 TI - Orientationally invariant indices of axon diameter and density from diffusion MRI. AB - This paper proposes and tests a technique for imaging orientationally invariant indices of axon diameter and density in white matter using diffusion magnetic resonance imaging. Such indices potentially provide more specific markers of white matter microstructure than standard indices from diffusion tensor imaging. Orientational invariance allows for combination with tractography and presents new opportunities for mapping brain connectivity and quantifying disease processes. The technique uses a four-compartment tissue model combined with an optimized multishell high-angular-resolution pulsed-gradient-spin-echo acquisition. We test the method in simulation, on fixed monkey brains using a preclinical scanner and on live human brains using a clinical 3T scanner. The human data take about one hour to acquire. The simulation experiments show that both monkey and human protocols distinguish distributions of axon diameters that occur naturally in white matter. We compare the axon diameter index with the mean axon diameter weighted by axon volume. The index differs from this mean and is protocol dependent, but correlation is good for the monkey protocol and weaker, but discernible, for the human protocol where greater diffusivity and lower gradient strength limit sensitivity to only the largest axons. Maps of axon diameter and density indices from the monkey and human data in the corpus callosum and corticospinal tract reflect known trends from histology. The results show orientationally invariant sensitivity to natural axon diameter distributions for the first time with both specialist and clinical hardware. This demonstration motivates further refinement, validation, and evaluation of the precise nature of the indices and the influence of potential confounds. PMID- 20580933 TI - Comparison of multivariate classifiers and response normalizations for pattern information fMRI. AB - A popular method for investigating whether stimulus information is present in fMRI response patterns is to attempt to "decode" the stimuli from the response patterns with a multivariate classifier. The sensitivity for detecting the information depends on the particular classifier used. However, little is known about the relative performance of different classifiers on fMRI data. Here we compared six multivariate classifiers and investigated how the response-amplitude estimate used (beta- or t-value) and different pattern normalizations affect classification performance. The compared classifiers were a pattern-correlation classifier, a k-nearest-neighbors classifier, Fisher's linear discriminant, Gaussian naive Bayes, and linear and nonlinear (radial-basis-function kernel) support vector machines. We compared these classifiers' accuracy at decoding the category of visual objects from response patterns in human early visual and inferior temporal cortex acquired in an event-related design with BOLD fMRI at 3T using SENSE and isotropic voxels of about 2-mm width. Overall, Fisher's linear discriminant (with an optimal-shrinkage covariance estimator) and the linear support vector machine performed best. The pattern-correlation classifier often performed similarly as those two classifiers. The nonlinear classifiers never performed better and sometimes significantly worse than the linear classifiers, suggesting overfitting. Defining response patterns by t-values (or in error standard-deviation units) rather than by beta estimates (in % signal change) to define the patterns appeared advantageous. Cross-validation by a leave-one stimulus-pair-out method gave higher accuracies than a leave-one-run-out method, suggesting that generalization to independent runs (which more safely ensures independence of the test set) is more challenging than generalization to novel stimuli within the same category. Independent selection of fewer more visually responsive voxels tended to yield better decoding performance for all classifiers. Normalizing mean and standard deviation of the response patterns either across stimuli or across voxels had no significant effect on decoding performance. Overall our results suggest that linear decoders based on t-value patterns may perform best in the present scenario of visual object representations measured for about 60min per subject with 3T fMRI. PMID- 20580934 TI - Occurrence of Biomphalaria cousini (Mollusca: Gastropoda) in Brazil and its susceptibility to Schistosoma mansoni (Platyhelminths: Trematoda). AB - In Brazil, there are three intermediate snail vectors and two potential hosts of Schistosoma mansoni. Previous studies showed three variant molecular profiles to B. amazonica and evidenced intraspecific variations using sequence data. In this context, the aim of this study was to verify whether such differences would correspond to either B. amazonica or B. cousini. The snails were morphologically identified; PCR-RFLP and sequencing were carried out. Besides, B. cousini were submitted to susceptibility experiments to S. mansoni. Noteworthy, morphological data of Brazilian specimens predominantly showed the morphology described for B. amazonica. Nevertheless, PCR-RFLP results exhibited three variant molecular profiles for the specimens previously identified as B. amazonica and the phylogenetic analyses showed two groups one to B. amazonica and another to B. cousini. Furthermore, B. cousini showed to be susceptible to S. mansoni. These results confirm the occurrence of B. cousini in Brazil and points to the risk of introduction of schistosomiasis mansoni into new areas. PMID- 20580935 TI - Comparative network clustering of direct repeats (DRs) and cas genes confirms the possibility of the horizontal transfer of CRISPR locus among bacteria. AB - CRISPRs are a diverse family of DNA repeat sequences that are widely distributed among archaea and bacteria. The CRISPR locus is usually composed of three key elements; direct repeats (DRs), spacer sequences and the cas genes. Although recent studies have suggested that spacers may be of extrachromosomal origin, the evolutionary origin of the other two elements of the CRISPR locus has remained unresolved. With the aim to elucidate the evolutionary origin and association of DRs and cas genes of the CRISPR locus, a comparative analysis of the evolutionary network clusters of DRs, cas1 and 16S rRNA genes sequences from 100 different bacteria was conducted. Significant matches of DR and cas1 gene clades imply that these CRISPR components are evolutionary closely linked and potentially evolving simultaneously as a whole locus. On the contrary, the prominent discordance between the CASS (DR and cas1) clades and the 16S rRNA clusters indicates that CRISPR locus has been transferred horizontally as a complete package. Sequence analysis also revealed that DR and cas1 genes are coevolving under analogous evolutionary pressure. This atypical evolutionary pattern also signifies the possibility of horizontal transfer event of CRISPR locus. PMID- 20580936 TI - Protein-DNA interactions in the promoter region of the Phycomyces carB and carRA genes correlate with the kinetics of their mRNA accumulation in response to light. AB - Carotene biosynthesis in Phycomyces is photoinducible and carried out by phytoene dehydrogenase (encoded by carB) and a bifunctional enzyme possessing lycopene cyclase and phytoene synthase activities (carRA). A light pulse followed by periods of darkness produced similar biphasic responses in the expression of the carB and carRA genes, indicating their coordinated regulation. Specific binding complexes were formed between the carB-carRA intergenic region and protein extracts from wild type mycelia grown in the dark or 8min after irradiation. These two conditions correspond to the points at which the expression of both genes is minimal, suggesting that these binding complexes are involved in the down-regulation of photocarotenogenesis in Phycomyces. Protein extracts from carotene mutants failed to form the dark retardation complex, suggesting a role of these genes in the regulation of photocarotenogenesis. In contrast, protein extracts from phototropic mutants formed dark retardation complexes identical to that of the wild type. PMID- 20580937 TI - Clathrin-dependent APP endocytosis and Abeta secretion are highly sensitive to the level of plasma membrane cholesterol. AB - Several lines of evidence support a strong relationship between cholesterol and Alzheimer's disease pathogenesis. Membrane cholesterol is known to modulate amyloid precursor protein (APP) endocytosis and amyloid-beta (Abeta) secretion. Here we show in a human cell line model of endocytosis (HEK293 cells) that cholesterol exerts these effects in a dose-dependent and linear manner, over a wide range of concentrations (-40% to +40% variations of plasma membrane cholesterol induced by methyl-beta-cyclodextrin (MBCD) and MBCD-cholesterol complex respectively). We found that the gradual effect of cholesterol is inhibited by small interference RNA-mediated downregulation of clathrin. Modulation of clathrin-mediated APP endocytosis by cholesterol was further demonstrated using mutants of proteins involved in the formation of early endosomes (dynamin2, Eps15 and Rab5). Importantly we show that membrane proteins other than APP are not affected by cholesterol to the same extent. Indeed clathrin-dependent endocytosis of transferrin and cannabinoid1 receptors as well as internalization of surface proteins labelled with a biotin derivative (sulfo NHS-SS-biotin) were not sensitive to variations of plasma membrane cholesterol from -40% to 40%. In conclusion clathrin-dependent APP endocytosis appears to be very sensitive to the levels of membrane cholesterol. These results suggest that cholesterol increase in AD could be responsible for the enhanced internalization of clathrin-, dynamin2-, Eps15- and Rab5-dependent endocytosis of APP and the ensuing overproduction of Abeta. PMID- 20580938 TI - Cholesterol-related genes in Alzheimer's disease. AB - Experimental data show that cholesterol can modulate central processes in the pathogenesis of Alzheimer's disease (AD). The epidemiological link between elevated plasma cholesterol at midlife and increased risk for AD and the possibility that 3-hydroxy-3-methylglutaryl-coenzym A reductase inhibitors (statins) may be protective against AD support a role of cholesterol metabolism in AD and have rendered it a potential therapeutic target in the treatment and prevention of the disease. The strong association of AD and AD endophenotypes with the APOE gene provides a genetic link between AD and cholesterol metabolism, because the apolipoprotein E (ApoE) is the most prevalent cholesterol transport protein in the central nervous system. Against this background several other genes with a role in cholesterol metabolism have been investigated for association with AD. In this review a compilation of genes related to cholesterol based on the information of the AmiGo gene ontology database is matched with the AlzGene database of AD candidate genes. 56 out of 149 (37.6%) genes with a relation to cholesterol metabolism have been investigated for association with AD. Given that only 660 out of about 23,000 (2.9%) genes have been assessed in hypothesis-driven candidate gene studies on AD, the cholesterol metabolic pathway is strongly represented among these genes. Among 34 cholesterol-related genes for which association with AD has been described APOE, CH25H, CLU, LDLR, SORL1 outstand with positive meta-analyses. However, it is unclear, if their association with AD is mediated by cholesterol-related mechanisms or by more specific direct effects of the respective proteins on Abeta metabolism. PMID- 20580940 TI - Juvenile polyps: recurrence in patients with multiple and solitary polyps. AB - BACKGROUND & AIMS: Juvenile polyps are benign hamartomas with neoplastic potential that are the most frequent gastrointestinal polyp of childhood. Most information about juvenile polyps in childhood comes from small published series that lack detailed outcome data. We sought to identify a large cohort of children with one or more polyps and analyze clinical characteristics, including polyp recurrence, which might contribute to the development of management guidelines. METHODS: A retrospective chart review study of patients with juvenile polyps of the colon was performed. Cases were identified by searching a single hospital pathology database from 1990 to 2009 for the diagnosis of juvenile polyps. Recorded information included basic demographics, family history, genetic testing, and colonoscopy and pathology reports. RESULTS: A total of 257 children (median age, 5.6 y; 61.5% male) with juvenile polyps were identified. Among 192 patients who underwent complete colonoscopy at initial diagnosis, 117 (60.9%) had a single polyp, 75 (39.1%) had multiple polyps, 8 (4.2%) had polyps restricted to the right colon, and a total of 1653 polyps were found during 350 colonoscopy examinations. Polyps recurred in 21 of 47 (44.7%) patients after initial eradication, including 3 (16.7%) of 18 presenting with a single polyp. Neoplasia was found in 10 of 257 (3.9%) patients (right colon in 7 patients). Germline DNA abnormalities in mothers against decapentaplegic Drosophila (SMAD4), bone morphogenetic protein receptor 1A (BMPR1A), and phosphatase and tensin homolog (PTEN) were detected in 10 of 23 (43.5%) patients with multiple polyps. CONCLUSIONS: Recurrent polyp formation is common in children with juvenile polyps and occurs in patients with multiple and solitary polyps. Standardized protocols for detecting polyp recurrence, associated gene mutations, and neoplasia should be developed for children with juvenile polyps. PMID- 20580939 TI - Transcriptional networks characterize ventricular dysfunction after myocardial infarction: a proof-of-concept investigation. AB - There is currently no method powerful enough to identify patients at risk of developing ventricular dysfunction after myocardial infarction (MI). We aimed to identify major mechanisms related to ventricular dysfunction to predict outcome after MI. Based on the combination of domain knowledge, protein-protein interaction networks and gene expression data, a set of potential biomarkers of ventricular dysfunction after MI was identified. Here we propose a new strategy for the prediction of ventricular dysfunction after MI based on "network activity indices" (NAI), which encode gene network-based signatures and distinguishes between prognostic classes. These models outperformed prognostic models based on standard differential expression analysis. NAI-based models reported high classification accuracy, with a maximum area under the receiver operating characteristic curve (AUC) of 0.75. Furthermore, the classification capacity of these models was validated by performing evaluations on an independent patient cohort (maximum AUC=0.75). These results suggest that transcriptional network based biosignatures can offer both powerful and biologically-meaningful prediction models of ventricular dysfunction after MI. This research reports a new integrative strategy for identifying transcriptional responses that characterize cardiac repair and for predicting clinical outcome after MI. It can be adapted to other clinical domains, such as those constrained by small molecular datasets and limited translational knowledge. Furthermore, it may reflect clinically-meaningful synergistic effects that cannot be identified by standard analyses. PMID- 20580941 TI - Primary pancreatic follicular lymphoma mimicking adenocarcinoma. PMID- 20580942 TI - A screening instrument for sleep apnea predicts airway maneuvers in patients undergoing advanced endoscopic procedures. AB - BACKGROUND & AIMS: Among patients undergoing advanced endoscopy, unrecognized obstructive sleep apnea (OSA) could predict sedation-related complications (SRCs) and the need for airway maneuvers (AMs). By using an OSA screening tool, we sought to define the prevalence of patients at high risk for OSA and to correlate OSA with the frequency of AMs and SRCs. METHODS: We enrolled 231 consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) (n = 176) and endoscopic ultrasound (n = 55). Propofol-based sedation and patient monitoring were performed by a nurse anesthetist and an anesthesiologist. A previously validated screening tool for OSA (STOP-BANG) was used to identify patients at high risk for OSA (score, > or =3 of 8; SB+) or low risk (SB-). AMs were defined as a chin lift, modified mask ventilation, nasal airway, bag-mask ventilation, and endotracheal intubation. SRCs were defined as any duration of pulse oximetry less than 90%, systolic blood pressure less than 90 mm Hg, apnea, or early procedure termination. RESULTS: The prevalence of SB+ was 43.3%. The frequency of hypoxemia was significantly higher among patients with SB+ than SB- (12.0% vs 5.2%; relative risk [RR], 1.83; 95% confidence interval [CI], 1.32 2.54). The rate of AMs was also significantly higher among SB+ (20.0%) compared with SB- (6.1%) patients (RR, 1.8; 95% CI, 1.3-2.4). These rates remained significant after adjusting for American Society of Anesthesiologists class 3 or higher (RR, 1.70; 95% CI, 1.28-2.2 for AMs; RR, 1.63; 95% CI, 1.19-2.25 for hypoxemia). Each element of the STOP-BANG was reported more commonly in SB+ patients (P < .0001 for each comparison). CONCLUSIONS: A significant number of patients undergoing advanced endoscopic procedures are at risk for OSA. AMs and hypoxemia occur at an increased frequency in these patients. PMID- 20580943 TI - How strong is the evidence that high-definition colonoscopy improves polyp detection rate compared with standard white-light colonoscopy? PMID- 20580944 TI - Genomics revolution: forging a path to the arrhythmia patient. PMID- 20580945 TI - Single momentary assessments are not reliable outcomes for clinical trials. AB - Patient reported outcomes (PROs) play an essential role in clinical trials, though questions have been raised about the accuracy of PROs using long recall periods. This paper examines the utility of a PRO employing a single momentary assessment of pain in a sample of community rheumatology patients. We explore the accuracy and reliability of a single assessment versus the average of multiple assessments taken over 1-week, which is considered a common outcome reporting period. A secondary analysis of 128 patients who monitored their pain intensity with momentary data collections several times a day for a week and 3 months later for another week allowed a comparison of randomly-selected single momentary assessments with the average of many assessments from the week. Results from cross-sectional analyses of the first week were that levels of pain measured by single points were not significantly different than the week average in 4 of 5 analyses, but these single-point assessments had much higher variance. Correlations of single-point and week averages were below 0.70. Longitudinal analysis of change scores across 3 months also demonstrated considerable unreliability of single-point measures, thus the statistical power generated by single-point assessments was considerably less than the more reliable week average. Our conclusion is that single momentary assessments, at least for representing an outcome over a period of a week, are not ideal measures. We discuss alternative measurement strategies for efficiently collecting PRO data for a 1-week period using end-of-day diaries or 7-day recall measures. PMID- 20580946 TI - Impairment of NFkappaB activity by unsaturated fatty acids. AB - Using a luciferase reporter gene assay, we identified polyunsaturated fatty acids (PUFA) to impair NF kappaB signaling. Furthermore, we could demonstrate the PUFA ability to derogate NF kappaB activity to be independent from the family the fatty acid belongs to. Instead, we found a relation between the number of bis allyl-methylene positions of the PUFA added and the NF kappaB activity of stimulated, long-term supplemented cells. The data presented provide new insights into the biological mechanisms PUFA exert their anti-inflammatory effects. Since suppression of NF kappaB activity could be of benefit in a number of inflammatory diseases as well as cancer, our findings are of clinical implication. According to our data dietary supplementation with PUFA-containing oils is likely to provide an at least palliative therapy for disorders linked to inappropriate NF kappaB signaling. PMID- 20580947 TI - Characterization of complex III deficiency and liver dysfunction in GRACILE syndrome caused by a BCS1L mutation. AB - A homozygous mutation in the complex III chaperone BCS1L causes GRACILE syndrome (intrauterine growth restriction, aminoaciduria, cholestasis, hepatic iron overload, lactacidosis). In control and patient fibroblasts we localized BCS1L in inner mitochondrial membranes. In patient liver, kidney, and heart BCS1L and Rieske protein levels, as well as the amount and activity of complex III, were decreased. Major histopathology was found in kidney and liver with cirrhosis and iron deposition, but of iron-related proteins only ferritin levels were high. In placenta from a GRACILE fetus, the ferrooxidases ceruloplasmin and hephaestin were upregulated suggesting association between iron overload and placental dysfunction. PMID- 20580948 TI - Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and atrophy. AB - Hereditary ataxias are genetic disorders characterized by uncoordinated gait and often poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. Many ataxias are autosomal dominant, but autosomal recessive (AR) disease occurs as well. Homozygosity mapping in a consanguineous family with three affected children with progressive cerebellar ataxia and atrophy revealed a candidate locus on chromosome 1, containing the CABC1/ADCK3 (the chaperone, ABC1 activity of bc1 complex homologue) gene. CABC1/ADCK3 is the homologue of the yeast Coq8 gene, which is involved in the ubiquinone biosynthesis pathway. Mutation analysis of this gene showed a homozygous nonsense mutation (c.1042C>T, p.R348X). Eight additional patients with AR cerebellar ataxia and atrophy were screened for mutations in the CABC1/ADCK3 gene. One patient was compound heterozygous for the same c.1042C>T mutation and a second nonsense mutation (c.1136T>A, p.L379X). Both mutations created a premature stop codon, triggering nonsense mediated mRNA decay as the pathogenic mechanism. We found no evidence of a Dutch founder for the c.1042C>T mutation in AR ataxia. We report here the first nonsense mutations in CABC1 that most likely lead to complete absence of a functional CABC1 protein. Our results indicate that CABC1 is an important candidate for mutation analysis in progressive cerebellar ataxia and atrophy on MRI to identify those patients, who may benefit from CoQ10 treatment. PMID- 20580949 TI - The inhibitory effect of polyvinylphosphonic acid on functional matrix metalloproteinase activities in human demineralized dentin. AB - This study has examined the use of polyvinylphosphonic acid (PVPA) as a potential matrix metalloproteinase (MMP) inhibitor and how brief cross-linking of demineralized dentin matrix that did not affect its mechanical properties enhanced the anti-MMP activity of PVPA. The anti-MMP potential of five PVPA concentrations (100-3000 microgml(-1)) was initially screened using a rhMMP-9 colorimetic assay. Demineralized dentin beams were treated with the same five concentrations of PVPA to collagen and then aged for 30 days in a calcium- and zinc-containing medium. The changes in modulus of elasticity, loss of dry mass and dissolution of collagen peptides were measured via three-point bending, precision weighing and hydroxyproline assay, respectively. All tested PVPA concentrations were highly effective (P<0.05) in inhibiting MMP-9. Ageing in the incubation medium did not significantly alter the modulus of elasticity of the five PVPA treatment groups. Conversely, aged dentin beams from the control group exhibited a significant decline in their modulus of elasticity (P<0.05) over time. Mass loss from the dentin beams and the corresponding increase in hydroxyproline in the medium in the five PVPA treatment groups were significantly lower than for the control (P<0.05). PVPA is a potent inhibitor of endogenous MMP activities in demineralized dentin. It may be used as an alternative to chlorhexidine to prevent collagen degradation within hybrid layers to extend the longevity of resin-dentin bonds. PMID- 20580950 TI - Visible light-induced crosslinkable gelatin. AB - A novel visible light-crosslinkable porcine gelatin was prepared for gelation and micropatterning. The preparation employed a photo-oxidation-induced crosslinking mechanism. First, furfuryl groups were incorporated into the gelatin. Second, the modified gelatin was mixed in water with Rose Bengal, which is a visible light sensitizer. Irradiation by visible light solidified the aqueous solution. In addition, when the solution was cast on a plate, dried and photo-irradiated in the presence of a photomask a micropattern was formed that matched the micropattern on the photomask. The gelatin-immobilized regions enhanced cell adhesion. It was also confirmed that the gelatin incorporating furfuryl and Rose Bengal have no significant toxicity. The photo-crosslinkable gelatin was employed as a direct pulp capping material in the dental field. Considering these results, this system could be useful as a new type of visible light-induced crosslinkable biosealant. PMID- 20580951 TI - The effect of type II collagen coating of chitosan fibrous scaffolds on mesenchymal stem cell adhesion and chondrogenesis. AB - The biocompatibility of chitosan and its similarity to glycosaminoglycans (GAG) make it attractive for cartilage tissue engineering. We have previously reported improved chondrogenesis but limited cell adhesion on chitosan scaffolds. Our objectives were to produce chitosan scaffolds coated with different densities of type II collagen and to evaluate the effect of this coating on mesenchymal stem cell (MSC) adhesion and chondrogenesis. Chitosan fibrous scaffolds were obtained by a wet spinning method and coated with type II collagen at two different densities. A polyglycolic acid mesh served as a reference group. The scaffolds were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and type II collagen content. Constructs were analyzed after MSCs seeding via live/dead assay, weight and DNA evaluations, SEM, and TEM. Constructs were cultured in chondrogenic medium for 21 days prior to quantitative analysis (weight, DNA, and GAG), SEM, TEM, histology, immunohistochemistry, and quantitative real time polymerase chain reaction. The cell attachment and distribution after seeding correlated with the density of type II collagen. The cell number, the matrix production, and the expression of genes specific for chondrogenesis were improved after culture in collagen coated chitosan constructs. These findings encourage the use of type II collagen for coating chitosan scaffolds to improve MSCs adhesion and chondrogenesis, and confirm the importance of biomimetic scaffolds for tissue engineering. PMID- 20580952 TI - When peptides fly: advances in Drosophila proteomics. AB - In the past decade, improvements in genome annotation, protein fractionation methods and mass spectrometry instrumentation resulted in rapid growth of Drosophila proteomics. This review presents the current status of proteomics research in the fly. Areas that have seen major advances in recent years include efforts to map and catalog the Drosophila proteome and high-throughput as well as targeted studies to analyze protein-protein interactions and post-translational modifications. Stable isotope labeling of flies and other applications of quantitative proteomics have opened up new possibilities for functional analyses. It is clear that proteomics is becoming an indispensable tool in Drosophila systems biology research that adds a unique dimension to studying gene function. PMID- 20580953 TI - Heard it through the grapevine: proteomic perspective on grape and wine. AB - Grapevine (Vitis ssp.) is currently considered as the most important fruit plant throughout the world, both due to its economic importance and to its role as a non climacteric model species. The relevance of the studies devoted to the dissection of grapevine biology and biochemistry underlines the great amount of attention that this plant has attracted over the last decade. The milestones among these studies are represented by the accomplishment of the genome sequencing programmes in 2007 [1,2]. Since then, the investigation of grape OMICS has been implemented, and the number of reports published on grape and wine protein investigations using proteomic techniques have significantly improved knowledge in the field. PMID- 20580955 TI - Single molecule tools: fluorescence based approaches, part A. Preface. PMID- 20580954 TI - Functional and biological analysis of Bcl-xL expression in human osteosarcoma. AB - Bcl-xL, a member of Bcl-2 protein family functioned as dominant regulators of apoptotic cell death, has been reported to play important roles in malignant transformation and tumor development. In the present study, our aim was to explore the roles of Bcl-xL overexpression and determine its possibility as a therapeutic target in human osteosarcoma. Real-time quantitative RT-PCR and Western blot or immunohistochemistry assays were performed to detect the expression of Bcl-xL mRNA and protein in human osteosarcoma cell lines or tissue samples. The expression of other Bcl-2 family proteins (Bcl-2, Mcl-1, Bim and Bik) in osteosarcoma tissues was also detected by immunohistochemistry. The associations of Bcl-xL mRNA expression with clinicopathologic factors and prognosis of osteosarcoma patients were evaluated. RNA interference or gene overexpression technologies were employed to downregulate or upregulate endogenous Bcl-xL expression in osteosarcoma cells and the effects of Bcl-xL downregulation or upregulation on phenotypes and chemo- or radiosensitivity of human osteosarcoma cells were analyzed. Finally, the mechanism of synergistic effects of Bcl-xL downregulation and chemo- or radiotherapy was explored by detecting the activity of caspase-3. The expression levels of Bcl-xL mRNA and protein in high metastatic osteosarcoma cells showed higher than those in low metastatic osteosarcoma cells. Moreover, the levels of Bcl-xL mRNA expression were significantly higher in osteosarcoma tissues than those in chondroma or corresponding non-tumor tissues (P<0.01), and osteosarcoma tissues showed stronger immunostaining of Bcl-xL protein than non-tumor tissues. The stronger staining of Bcl-2 and Mcl-1 proteins was also observed, while the staining of pro apoptotic proteins (Bim and Bik) was significantly weaker or not detected in osteosarcoma tissues. The higher levels of Bcl-xL mRNA expression were significantly correlated with advanced clinical stage (P=0.005) or hematogenous metastasis (P=0.001) of osteosarcoma patients. Osteosarcoma patients with higher Bcl-xL mRNA expression showed a poorer survival compared with those with lower expression (P=0.039). Bcl-xL downregulation or upregulation could significantly reduce or increase the proliferation capacity of osteosarcoma cells. Furthermore, Bcl-xL downregulation could significantly enhance in vitro chemo- or radiosensitivity of osteosarcoma cells, which might be associated with elevated activity of caspase-3. Taken together, overexpression of Bcl-xL may play important roles in osteosarcoma progression and this molecule will be a potential chemo- or radiotherapeutic molecular target for osteosarcoma therapy. PMID- 20580956 TI - Star polymer surface passivation for single-molecule detection. AB - Poly(ethylene oxide) (PEO) is known as an excellent coating material to minimize nonspecific protein adsorption. For an examination of biomolecules attached to surfaces with sensitivities down to the single-molecule level, demands on the surface additionally comprise low-intrinsic fluorescence of the coating material and a possibility to immobilize biomolecules in their functional conformation. One strategy that combines the protein-resistant properties of PEO with chemical functionality is the use of star-shaped PEOs that allow for interpolymer cross linking. Our system consists of six-arm PEO-based star polymers functionalized with reactive isocyanate groups at the ends of the polymer chain. The isocyante groups allow intermolecular cross-linking so that high grafting densities may be achieved, which render the surfaces extremely resistant to protein adsorption. Application by spin coating offers a simple procedure for the preparation of minimally interacting surfaces. The reactive end groups may be further biofunctionalized to recognize specific biomolecules such as streptavidin or His tagged proteins in specific geometries or as single isolated molecules. These properties, together with the advantageous chemical properties of PEO, render the surfaces ideal for immobilizing proteins with detection limits down to the single molecule level. This chapter focuses on the preparation of substrates that are suitable for single-molecule experiments. Besides a detailed description of surface preparation, two examples for the single-molecule detection of immobilized proteins, nucleosomes and RNase H, are presented that demonstrate the advantages of the star-polymer derived coatings over linear-grafted PEO. PMID- 20580957 TI - Azide-specific labeling of biomolecules by Staudinger-Bertozzi ligation phosphine derivatives of fluorescent probes suitable for single-molecule fluorescence spectroscopy. AB - We describe the synthesis of phosphine derivatives of three fluorescent probes that have a brightness and photostability suitable for single-molecule fluorescence spectroscopy and microscopy: Alexa488, Cy3B, and Alexa647. In addition, we describe procedures for use of these reagents in azide-specific, bioorthogonal labeling through Staudinger-Bertozzi ligation, as well as procedures for the quantitation of labeling specificity and labeling efficiency. The reagents and procedures of this report enable chemoselective, site-selective labeling of azide-containing biomolecules for single-molecule fluorescence spectroscopy and microscopy. PMID- 20580958 TI - Preparation of fluorescent pre-mRNA substrates for an smFRET study of pre-mRNA splicing in yeast. AB - The spliceosome is a complex small nuclear (sn)RNA-protein machine that removes introns from pre-mRNAs via two successive phosphoryl transfer reactions. For each splicing event, the spliceosome is assembled de novo on a pre-mRNA substrate and a complex series of assembly steps leads to the active conformation. To comprehensively monitor pre-mRNA conformational dynamics during spliceosome assembly, we developed a strategy for single-molecule FRET (smFRET) that utilizes a small, efficiently spliced yeast pre-mRNA, Ubc4, in which donor and acceptor fluorophores are placed in the exons adjacent to the 5' and 3' splice sites. In this chapter, we describe the identification of Ubc4 pre-mRNA that is efficiently spliced in vitro and the methods we have developed for the chemical synthesis of fluorescent Ubc4 pre-mRNA for smFRET. PMID- 20580959 TI - Nanovesicle trapping for studying weak protein interactions by single-molecule FRET. AB - Protein-protein interactions are fundamental biological processes. While strong protein interactions are amenable to many characterization techniques including crystallography, weak protein interactions are challenging to study because of their dynamic nature. Single-molecule fluorescence resonance energy transfer (smFRET) can monitor dynamic protein interactions in real time, but are generally limited to strong interacting pairs because of the low concentrations needed for single-molecule detection. Here, we describe a nanovesicle trapping approach to enable smFRET study of weak protein interactions at high effective concentrations. We describe the experimental procedures, summarize the application in studying the weak interactions between intracellular copper transporters, and detail the single-molecule kinetic analysis of bimolecular interactions involving three states. Both the experimental approach and the theoretical analysis are generally applicable to studying many other biological processes at the single-molecule level. PMID- 20580960 TI - Droplet confinement and fluorescence measurement of single molecules. AB - We describe a method for molecular confinement and single-fluorophore sensitive measurement in aqueous nanodroplets in oil. The sequestration of individual molecules in droplets has become a useful tool in genomics and molecular evolution. Similarly, the use of single fluorophores, or pairs of fluorophores, to study biomolecular interactions and structural dynamics is now common. Most often these single-fluorophore sensitive measurements are performed on molecules that are surface attached. Confinement via surface attachment permits molecules to be located and studied for a prolonged period of time. For molecules that denature on surfaces, for interactions that are transient or out-of-equilibrium, or to observe the dynamic equilibrium of freely diffusing reagents, surface attachment may not be an option. In these cases, droplet confinement presents an alternative method for molecular confinement. Here, we describe this method as used in single-fluorophore sensitive measurement and discuss its advantages, limitations, and future prospects. PMID- 20580962 TI - Single-molecule spectroscopy using microfluidic platforms. AB - Microfluidics serves as a convenient platform for single-molecule experiments by providing manipulation of small amounts of liquids and micron-sized particles. An adapted version of capillary electrophoresis (CE) on a microchip can be utilized to separate chemical species with high resolution based on their ionic mobilities (i.e., charges and sizes), but identification of separated species is not trivial, especially for complex mixtures of sticky biomolecules. We describe here how to use a surfactant mixture system for CE on a poly(dimethylsiloxane) (PDMS) microchip, capture separated peaks within a 50-pl chamber using microvalves, analyze the fluorescence signals with correlation spectroscopy to extract molecular diffusion characteristics, and to identify the biomolecular clusters in a model immunocomplex system. PMID- 20580961 TI - Single-molecule fluorescence spectroscopy using phospholipid bilayer nanodiscs. AB - Nanodiscs are a new class of model membranes that are being used to solubilize and study a range of integral membrane proteins and membrane-associated proteins. Unlike other model membranes, the Nanodisc bilayer is bounded by a scaffold protein coat that confers enhanced stability and a narrow particle size distribution. The bilayer diameter can be precisely controlled by changing the diameter of the protein coat. All these properties make Nanodiscs excellent model membranes for single-molecule fluorescence applications. In this chapter, we describe our work using Nanodiscs to apply total internal reflection fluorescence microscopy (TIRFM), fluorescence correlation spectroscopy (FCS), and Forster resonance energy transfer (FRET) to study the integral membrane protein cytochrome P450 3A4 and the peripheral membrane-binding proteins islet amyloid polypeptide (IAPP) and alpha-synuclein, respectively. The monodisperse size distribution of Nanodiscs enhances control over the oligomeric state of the membrane protein of interest, and facilitates accurate solution-based measurements as well. Nanodiscs also comprise an excellent system to stably immobilize integral membrane proteins in a bilayer without covalent modification, enabling a range of surface-based experiments where accurate localization of the protein of interest is required. PMID- 20580963 TI - Detection of protein-protein interactions in the live cell plasma membrane by quantifying prey redistribution upon bait micropatterning. AB - Our understanding of complex biological systems is based on high-quality proteomics tools for the parallelized detection and quantification of protein interactions. Current screening platforms, however, rely on measuring protein interactions in rather artificial systems, rendering the results difficult to confer on the in vivo situation. We describe here a detailed protocol for the design and the construction of a system to detect and quantify interactions between a fluorophore-labeled protein ("prey") and a membrane protein ("bait") in living cells. Cells are plated on micropatterned surfaces functionalized with antibodies to the bait exoplasmic domain. Bait-prey interactions are assayed via the redistribution of the fluorescent prey. The method is characterized by high sensitivity down to the level of single molecules, the capability to detect weak interactions, and high throughput, making it applicable as a screening tool. The proof-of-concept is demonstrated for the interaction between CD4, a major coreceptor in T-cell signaling, and Lck, a protein tyrosine kinase essential for early T-cell signaling. PMID- 20580964 TI - Analysis of complex single-molecule FRET time trajectories. AB - Single-molecule methods have given researchers the ability to investigate the structural dynamics of biomolecules at unprecedented resolution and sensitivity. One of the preferred methods of studying single biomolecules is single-molecule fluorescence resonance energy transfer (smFRET). The popularity of smFRET stems from its ability to report on dynamic, either intra- or intermolecular interactions in real-time. For example, smFRET has been successfully used to characterize the role of dynamics in functional RNAs and their protein complexes, including ribozymes, the ribosome, and more recently the spliceosome. Being able to reliably extract quantitative kinetic and conformational parameters from smFRET experiments is crucial for the interpretation of their results. The need for efficient, unbiased analysis routines becomes more evident as the systems studied become more complex. In this chapter, we focus on the practical utility of statistical algorithms, particularly hidden Markov models, to aid in the objective quantification of complex smFRET trajectories with three or more discrete states, and to extract kinetic information from the trajectories. Additionally, we present a method for systematically eliminating transitions associated with uncorrelated fluorophore behavior that may occur due to dye anisotropy and quenching effects. We also highlight the importance of data condensation through the use of various transition density plots to fully understand the underlying conformational dynamics and kinetic behavior of the biological macromolecule of interest under varying conditions. Finally, the application of these techniques to studies of pre-mRNA conformational changes during eukaryotic splicing is discussed. PMID- 20580965 TI - Single-molecule fluorescence studies of intrinsically disordered proteins. AB - Intrinsically disordered proteins (IDPs) (also referred to as natively unfolded proteins) play critical roles in a variety of cellular processes such as transcription and translation and also are linked to several human diseases. Biophysical studies of IDPs present unusual experimental challenges due in part to their broad conformational heterogeneity and potentially complex binding induced folding behavior. By minimizing the averaging over an ensemble (which is typical of most conventional experiments), single-molecule fluorescence (SMF) techniques have recently begun to add advanced capabilities for structural studies to the experimental arsenal of IDP investigators. Here, we briefly discuss a few common SMF methods that are particularly useful for IDP studies, including SMF resonance energy transfer and fluorescence correlation spectroscopy, along with site-specific protein-labeling methods that are essential for application of these methods to IDPs. We then present an overview of a few studies in this area, highlighting how SMF methods are being used to gain valuable information about two amyloidogenic IDPs, the Parkinson's disease linked alpha-synuclein and the NM domain of the yeast prion protein Sup 35. SMF experiments provided new information about the proteins' rapidly fluctuating IDP forms, and the complex alpha-synuclein folding behavior upon its binding to lipid and membrane mimics. We anticipate that SMF and single-molecule methods, in general, will find broad application for structural and mechanistic studies of a wide variety of IDPs, both of their disordered conformations, and their ordered ensembles relevant for function and disease. PMID- 20580966 TI - Measuring the energetic coupling of tertiary contacts in RNA folding using single molecule fluorescence resonance energy transfer. AB - Tertiary contacts are critical to stabilizing the folded conformations of structured RNAs. In some cases, these contacts have been shown to interact with positive cooperativity. Measuring the energetic coupling of tertiary contact formation is among the most basic physical characterizations of a structured RNA. With proper experimental design, single-molecule fluorescence resonance energy transfer (smFRET) allows the rigorous determination of the energetic coupling. This chapter aims to provide a general experimental approach to measuring the energetic coupling of tertiary contacts, using smFRET. PMID- 20580967 TI - A highly purified, fluorescently labeled in vitro translation system for single molecule studies of protein synthesis. AB - Single-molecule fluorescence resonance energy transfer (smFRET) has emerged as a powerful tool for mechanistic investigations of increasingly complex biochemical systems. Recently, we and others have successfully used smFRET to directly investigate the role of structural dynamics in the function and regulation of the cellular protein synthesis machinery. A significant challenge to these experiments, and to analogous experiments in similarly complex cellular machineries, is the need for specific and efficient fluorescent labeling of the biochemical system at locations that are both mechanistically informative and minimally perturbative to the biological activity. Here, we describe the development of a highly purified, fluorescently labeled in vitro translation system that we have successfully designed for smFRET studies of protein synthesis. The general approaches we outline should be amenable to single molecule fluorescence studies of other complex biochemical systems. PMID- 20580969 TI - DNA curtains for high-throughput single-molecule optical imaging. AB - Single-molecule approaches provide a valuable tool in the arsenal of the modern biologist, and new discoveries continue to be made possible through the use of these state-of-the-art technologies. However, it can be inherently difficult to obtain statistically relevant data from experimental approaches specifically designed to probe individual reactions. This problem is compounded with more complex biochemical reactions, heterogeneous systems, and/or reactions requiring the use of long DNA substrates. Here we give an overview of a technology developed in our laboratory, which relies upon simple micro- or nanofabricated structures in combination with "bio-friendly" lipid bilayers, to align thousands of long DNA molecules into defined patterns on the surface of a microfluidic sample chamber. We call these "DNA curtains," and we have developed several different versions varying in complexity and DNA substrate configuration, which are designed to meet different experimental needs. This novel approach to single molecule imaging provides a powerful experimental platform that offers the potential for concurrent observation of hundreds or even thousands of protein-DNA interactions in real time. PMID- 20580968 TI - Watching individual proteins acting on single molecules of DNA. AB - In traditional biochemical experiments, the behavior of individual proteins is obscured by ensemble averaging. To better understand the behavior of proteins that bind to and/or translocate on DNA, we have developed instrumentation that uses optical trapping, microfluidic solution delivery, and fluorescent microscopy to visualize either individual proteins or assemblies of proteins acting on single molecules of DNA. The general experimental design involves attaching a single DNA molecule to a polystyrene microsphere that is then used as a microscopic handle to manipulate individual DNA molecules with a laser trap. Visualization is achieved by fluorescently labeling either the DNA or the protein of interest, followed by direct imaging using high-sensitivity fluorescence microscopy. We describe the sample preparation and instrumentation used to visualize the interaction of individual proteins with single molecules of DNA. As examples, we describe the application of these methods to the study of proteins involved in recombination-mediated DNA repair, a process essential for the maintenance of genomic integrity. PMID- 20580970 TI - Scanning FCS for the characterization of protein dynamics in live cells. AB - Scanning fluorescence correlation spectroscopy (sFCS) is the generic term for a group of fluorescence correlation techniques where the measurement volume is moved across the sample in a defined way. The introduction of scanning is motivated by its ability to alleviate or remove several distinct problems often encountered in standard FCS, and thus, to extend the range of applicability of fluorescence correlation methods in biological systems. These problems include poor statistical accuracy in measurements with slowly moving molecules, photobleaching, optical distortions affecting the calibration of the measurement volume, membrane instabilities, etc. Here, we present an overview of sFCS methods, explaining their benefits, implementation details, requirements, and limitations, as well as relations to each other. Further, we give examples of different sFCS implementations as applied to cellular systems, namely large circle sFCS to measure protein dynamics in embryo cortex and line sFCS to measure protein diffusion and interactions in unstable membranes. PMID- 20580971 TI - Observing protein interactions and their stoichiometry in living cells by brightness analysis of fluorescence fluctuation experiments. AB - A single fluorescently labeled protein generates a short burst of light whenever it passes through a tiny observation volume created within a biological cell. The average amplitude of the burst is related to the stoichiometry of the fluorescently labeled protein complex. Fluorescence fluctuation spectroscopy quantifies the burst amplitude by introducing the brightness parameter. Brightness provides a spectroscopic marker for observing protein interactions and their stoichiometry directly inside cells. Not all fluorescent proteins are suitable for brightness experiments. Here we discuss how brightness properties of the fluorophore influence brightness measurements and how to identify a well behaved fluorescent protein. Protein interactions and stoichiometry are determined from a brightness titration. Experimental details of brightness titration measurements are described together with the necessary calibration and control experiments. PMID- 20580972 TI - Detection of individual endogenous RNA transcripts in situ using multiple singly labeled probes. AB - Measurements of gene expression within single cells have revealed startling variability otherwise hidden in bulk measurements. Here, we present an in situ hybridization method capable of detecting individual mRNA molecules, thus permitting the accurate quantification and localization of mRNA within fixed sample. Our in situ protocol involves probing the target mRNA using a series of singly labeled oligonucleotide probes. This method is simple to implement and is applicable to a variety of biological samples. We also discuss some aspects of image processing required for analyzing the resulting data. PMID- 20580974 TI - Single-molecule sequencing: sequence methods to enable accurate quantitation. AB - Helicos Single-Molecule Sequencing provides a unique view of genome biology through direct sequencing of cellular and extracellular nucleic acids in an unbiased manner, providing both quantitation and sequence information. Using a simple sample preparation, involving no ligation or amplification, genomic DNA is sheared, tailed with poly-A and hybridized to the flow-cell surface containing oligo-dT for initiating sequencing-by-synthesis. RNA measurements involving direct RNA hybridization to the flow cell allows for the direct sequencing and quantitation of RNA molecules. From these methods, a diverse array of applications has now been successfully demonstrated with the Helicos Genetic Analysis System, including human genome sequencing for accurate variant detection, ChIP Seq studies involving picogram quantities of DNA obtained from small cell numbers, copy number variation studies from both fresh tumor tissue and formalin-fixed paraffin-embedded tissue and archival tissue samples, small RNA studies leading to the identification of new classes of RNAs, and the direct capture and sequencing of nucleic acids from cell quantities as few as 400 cells with our end goal of single cell measurements. Helicos methods provide an important opportunity to researchers, including genomic scientists, translational researchers, and diagnostic experts, to benefit from biological measurements at the single-molecule level. This chapter will describe the various methods available to researchers. PMID- 20580973 TI - Single mRNA tracking in live cells. AB - Asymmetric distribution of mRNA is a prevalent phenomenon observed in diverse cell types. The posttranscriptional movement and localization of mRNA provides an important mechanism to target certain proteins to specific cytoplasmic regions of their function. Recent technical advances have enabled real-time visualization of single mRNA molecules in living cells. Studies analyzing the motion of individual mRNAs have shed light on the complex RNA transport system. This chapter presents an overview of general approaches for single particle tracking and some methodologies that are used for single mRNA detection. PMID- 20580975 TI - Real-time DNA sequencing from single polymerase molecules. AB - Pacific Biosciences has developed a method for real-time sequencing of single DNA molecules (Eid et al., 2009), with intrinsic sequencing rates of several bases per second and read lengths into the kilobase range. Conceptually, this sequencing approach is based on eavesdropping on the activity of DNA polymerase carrying out template-directed DNA polymerization. Performed in a highly parallel operational mode, sequential base additions catalyzed by each polymerase are detected with terminal phosphate-linked, fluorescence-labeled nucleotides. This chapter will first outline the principle of this single-molecule, real-time (SMRT) DNA sequencing method, followed by descriptions of its underlying components and typical sequencing run conditions. Two examples are provided which illustrate that, in addition to the DNA sequence, the dynamics of DNA polymerization from each enzyme molecules is directly accessible: the determination of base-specific kinetic parameters from single-molecule sequencing reads, and the characterization of DNA synthesis rate heterogeneities. PMID- 20580976 TI - Calpainopathy presenting as foot drop in a 41 year old. AB - Mutations in the gene encoding muscle-specific calpain 3 protease cause limb girdle muscular dystrophy type 2A. Calpainopathy is characterised by progressive symmetrical atrophy of pelvic, scapular and trunk muscles with an elevated creatine kinase. Most patients develop symptoms in childhood and lose the ability to walk by the age of 40 years. We describe a man who presented with foot drop at the age of 41 years, together with neurophysiological, histopathological and genetic data. This is the first report of calpainopathy presenting as foot drop, and widens the phenotype associated with this disease. PMID- 20580977 TI - The international follow-up of individuals potentially exposed to polonium-210 in London 2006. AB - OBJECTIVES: Following a death from polonium-210 ((210)Po), contamination was found at several sites in London. This paper describes the UK Health Protection Agency's follow-up and assessment of individuals resident overseas who were potentially exposed to (210)Po. STUDY DESIGN: Descriptive follow-up study. METHODS: Individuals were classified into three exposure groups (higher, lower and unknown). Presence and degree of internal contamination were measured by 24-h urinary (210)Po activity (mBq/day). Results over 30mBq/day were taken to indicate probable contact with (210)Po in this incident. Dose assessments were conducted to determine degree of exposure and to identify individuals requiring further follow-up. RESULTS: Overall, 664 potentially exposed persons from 52 countries and territories were identified. Of these, 157 (24%) were in the higher exposure category, and urinary measurements were reported for 31% (48/157). Results for 19% (9/48) of those at higher exposure were more than 30mBq/day. For those at lower exposure, the percentage was 4% (3/68). Results above 30mBq/day were significantly more likely to be reported for the higher exposure category than the lower exposure category (Fisher's exact test P=0.010). Reported dose assessments suggested that identified individuals were not at increased health risk in the long term. Challenges and practical lessons were identified during the investigation. CONCLUSION: The results suggest that it is unlikely that any overseas resident had significant internal contamination with (210)Po. However, this incident clearly demonstrated the scale of international involvement likely to be necessary in other public health emergencies in large cities. The lessons identified have implications for the international health community, particularly with regard to the follow-up of individuals exposed to radiation in one country who then travel to another. PMID- 20580978 TI - Genetic typing of porcine circovirus type 2 (PCV-2) isolates from Slovakia. AB - Of 120 clinical specimens obtained from pigs bred on 28 PMWS-affected farms in Slovakia, porcine circovirus type 2 (PCV-2) was detected by single PCR in 77 samples. A short 224 bp fragment of ORF2 was used for preliminary grouping of isolates by phylogenetic analysis. Nucleotide sequences of the entire ORF2 region provided more precise genetic typing and segregation of preselected isolates (n=10) into two known genotypes, PCV-2a (n=1) and PCV-2b (n=9). Complete genome sequencing of three selected isolates allowed their definitive grouping into genotype PCV-2b, cluster 1A or genotype PCV-2a, cluster 2D. No correlation between the mutations and the geographic origin of isolates was observed. Results confirmed that many PCV-2 isolates are genetically very stable since similar viruses circulate in Central and Western Europe. PMID- 20580980 TI - Comment on "Important role of reaction field in photodegradation of deca bromodiphenyl ether: Theoretical and experimental investigations of solvent effects" by Q. Xie, J. Chen, J. Shao, C. Chen, H. Zhao, C. Hao [Chemosphere 76(11) (2009) 1486-1490]. PMID- 20580981 TI - Microscopic clot fragment evidence of biochemo-mechanical degradation effects in thrombolysis. AB - INTRODUCTION: Although fibrinolytic treatment has been used for decades, the interactions between the biochemical mechanisms and the mechanical forces of the streaming blood remain incompletely understood. Analysis of the blood clot surface in vitro was employed to study the concomitant effect of blood plasma flow and recombinant tissue plasminogen activator (rt-PA) on the degradation of retracted, non-occlusive blood clots. Our hypothesis was that a faster tangential plasma flow removed larger fragments and resulted in faster overall thrombolysis. MATERIALS AND METHODS: Retracted model blood clots were prepared in an optical microscopy chamber and connected to an artificial perfusion system with either no flow, or plasma flow with a velocity of 3 cm/s or 30 cm/s with or without added rt-PA at 2 microg/ml. The clot surface was dynamically imaged by an optical microscope for 30 min with 15s intervals. RESULTS: The clot fragments removed during rt-PA mediated thrombolysis ranged in size from that of a single red blood cell to large agglomerates composed of more than a thousand red blood cells bound together by partly degraded fibrin. The average and the largest discrete clot area change between images in adjacent time frames were significantly higher with the faster flow than with the slow flow (14,000 microm(2) and 160,000 microm(2) vs. 2200 microm(2) and 10,600 microm(2)). CONCLUSIONS: On the micrometer scale, thrombolysis consists of sequential removal of clot fragments from the clot surface. With increasing tangential plasma flow velocity, the size of the clot fragments and the overall rate of thrombolysis increases. PMID- 20580982 TI - Conditional stimulation by galanin of saccharin and ethanol consumption under free and response contingent access. AB - Prior research has shown that the neuropeptide galanin strongly stimulates food intake in sated rats when food is made freely available. However, when access to food is made contingent upon lever pressing on a reinforcement schedule, no such stimulation occurs. This dissociation is consistent with the theorized "behavioral energizing" function of the ascending mesolimbic dopamine system, which purports that this ascending dopamine system is involved in only the goal directed effort maintaining (appetitive) and not the hedonic (consummatory) aspects of reward. Further, these results suggest that galanin may play an inhibitory role therein, or itself may be inhibited by mesolimbic dopamine activity underlying instrumental behavior. Prior research into this phenomenon has only utilized caloric foods or water, so the current work assessed the generality of this finding by determining if a similar dissociation also applies to commodities with other properties. For the present experiments, two commodities which varied in the dimensions of palatability and caloric load but which are both known to serve as reinforcers in other settings were chosen. In the first experiment, under the current single commodity free consumption test conditions shown to be sensitive to galanin effects of food and water consumption, galanin did not significantly alter the consumption of caloric laden but poorly palatable 7% alcohol solution. However, in the second experiment, galanin significantly increased free consumption of a highly palatable but non caloric 0.2% saccharin solution but not when operant responding was required for access to saccharin, extending the basic appetitive-consummatory dissociation observed for food. Taken together, these results suggest that the gustatory properties may be a specific factor involved in galanin stimulation of free consumption, and that there may be a continuum of influence of galanin based on the relative "elasticity" of the commodities as reinforcers. PMID- 20580983 TI - Propofol pretreatment increases antidepressant-like effects induced by acute administration of ketamine in rats receiving forced swimming test. AB - Animal and clinical studies have demonstrated that ketamine has quick, obvious and persistent antidepressant-like effect, but such side effects as cardiovascular system excitement and hallucinogenic activity have limited its clinical application. Intravenous anesthetic propofol can remarkably inhibit or eliminate ketamine's side effects including cardiovascular system excitement and hallucinogenic activity even in a sub-anesthesia dose. However, effect of propofol on rapid antidepressant-like action induced by ketamine still remains unclear. The present study aimed to investigate effect of pretreatment with propofol on the ketamine-induced rapid antidepressant-like action in rats receiving forced swimming test. Open field test and forced swimming test were used to investigate behavior changes of rats receiving different medication. Expression of brain derived neurotrophic factors (BDNF) and a-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid (AMPA) pGluR1-Ser845 in hippocampus was measured with sandwich-ELISA and Western Blot, respectively. Results demonstrated that rats receiving propofol alone showed neither antidepressant-like effects nor increased BDNF content; pretreatment with propofol could increase the ketamine induced antidepressant-like effects and the expression of AMPA pGluR1-Ser845 in hippocampus, but could not further reinforce the increased BDNF content induced by ketamine in hippocampus; after AMPA receptor was antagonized, the strengthening effect of propofol on ketamine-induced antidepressant-like action significantly decreased. The results indicated that propofol in a sub-anesthetic dose could increase the ketamine-induced antidepressant-like effect. PMID- 20580984 TI - Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers. AB - Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. We investigated possible relationships between five TPH1 gene polymorphisms and cerebrospinal fluid (CSF) concentrations of the major serotonin metabolite 5 hydroxyindoleacetic acid (5-HIAA), the major dopamine metabolite homovanillic acid (HVA), and the major norepinephrine metabolite 3-methoxy-4 hydroxyphenylglycol (MHPG) in healthy volunteers (n=132). The G-allele of the TPH1 rs4537731 (A-6526G) polymorphism was associated with 5-HIAA and HVA, but not MHPG concentrations. None of the other four TPH1 polymorphisms (rs211105, rs1800532, rs1799913 and rs7933505) were significantly associated with any of the monoamine metabolite concentrations. Two (rs4537731G/rs211105T/rs1800532C/rs1799913C/rs7933505G and rs4537731A/rs211105T/rs1800532C/rs1799913C/rs7933505G) of five common TPH1 five allele haplotypes were associated with 5-HIAA and HVA concentrations in opposite directions. None of the common haplotypes was associated with MHPG concentrations in the CSF. The results suggest that TPH1 gene variation participates in the regulation of serotonin and dopamine turnover rates in the central nervous system of healthy human subjects. PMID- 20580985 TI - Food safety performance indicators to benchmark food safety output of food safety management systems. AB - There is a need to measure the food safety performance in the agri-food chain without performing actual microbiological analysis. A food safety performance diagnosis, based on seven indicators and corresponding assessment grids have been developed and validated in nine European food businesses. Validation was conducted on the basis of an extensive microbiological assessment scheme (MAS). The assumption behind the food safety performance diagnosis is that food businesses which evaluate the performance of their food safety management system in a more structured way and according to very strict and specific criteria will have a better insight in their actual microbiological food safety performance, because food safety problems will be more systematically detected. The diagnosis can be a useful tool to have a first indication about the microbiological performance of a food safety management system present in a food business. Moreover, the diagnosis can be used in quantitative studies to get insight in the effect of interventions on sector or governmental level. PMID- 20580986 TI - The use of Lactobacillus brevis PS1 to in vitro inhibit the outgrowth of Fusarium culmorum and other common Fusarium species found on barley. AB - A total of 129 lactic acid bacteria (LAB) were screened for antifungal activity against common Fusarium spp. isolated from brewing barley. Four out of the five most inhibiting isolates were identified as Lactobacillus brevis, whereas one belonged to Weissella cibaria. L. brevis PS1, the isolate showing the largest inhibition spectrum, was selected and the influence of its freeze-dried cell-free supernatant (cfsP) on germination of macroconidia as well as mycelia growth was investigated using Fusarium culmorum as target organism.Addition of cfsP into the growth medium at concentrations > or = 2% altered the growth morphology of F.culmorum, whereas at concentrations > 5% the outgrowth of germ tubes from macroconidia was delayed and distorted. The presence of 10% cfsP completely inhibited the outgrowth of F. culmorum macroconidia. The activity of the compounds produced by L. brevis PS1 was higher at low pH values, i.e. pH < 5. Heating and/or proteolytic treatment reduced the inhibitory activity of cfsP, indicating that L. brevis produces organic acids and proteinaceous compounds which are active against Fusarium spp. PMID- 20580987 TI - Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers. AB - BACKGROUND & AIMS: Albumin dialysis using molecular adsorbent recirculating system (MARS) is a new procedure for treating resistant pruritus from cholestasis, but it is usually published as a case report or a short series. Therefore, we analyzed patients with resistant pruritus treated with MARS from three centers, to assess the changes on pruritus and the indices of cholestasis. METHODS: Twenty patients (12 female, mean age: 51+/-3.4 years) with chronic cholestatic liver disease or chronic liver-graft rejection were evaluated. The severity of pruritus was assessed using a visual analogue scale (VAS) before and after treatment, and 30 days thereafter. Liver tests, including total bilirubin, alkaline phosphatase, gamma-glutamyl-transferase, cholesterol, triglycerides, and total bile acid were also determined, as well as the number of sessions and the coupled procedure (dialysis or perfusion). RESULTS: Albumin dialysis resulted in a decrease of pruritus (VAS: from 70.2+/-4.8 to 20.1+/-4.2, p<0.001), which partially resumed after 30 days (38.7+/-6.6). VAS decreased by 72% immediately after treatment and by 51% after 1 month. Pruritus decreased in all but one patient. MARS resulted in a significant bile acid decrease of 41% after treatment and by 37% after 1 month. The effect of MARS on pruritus and markers of cholestasis was similar in patients with different diseases and was independent of the coupled procedure. The improvement of pruritus in individuals was positive in 75% of patients. No major adverse effects were observed. CONCLUSIONS: Albumin dialysis using MARS is an effective procedure for managing resistant pruritus in most patients with chronic cholestasis and graft rejection. PMID- 20580988 TI - Integrating science and business models of sustainability for environmentally challenging industries such as secondary lead smelters: a systematic review and analysis of findings. AB - Secondary lead smelters (SLS) represent an environmentally-challenging industry as they deal with toxic substances posing potential threats to both human and environmental health, consequently, they operate under strict government regulations. Such challenges have resulted in the significant reduction of SLS plants in the last three decades. In addition, the domestic recycling of lead has been on a steep decline in the past 10 years as the amount of lead recovered has remained virtually unchanged while consumption has increased. Therefore, one may wonder whether sustainable development can be achieved among SLS. The primary objective of this study was to determine whether a roadmap for sustainable development can be established for SLS. The following aims were established in support of the study objective: (1) to conduct a systematic review and an analysis of models of sustainable systems with a particular emphasis on SLS; (2) to document the challenges for the U.S. secondary lead smelting industry; and (3) to explore practices and concepts which act as vehicles for SLS on the road to sustainable development. An evidence-based methodology was adopted to achieve the study objective. A comprehensive electronic search was conducted to implement the aforementioned specific aims. Inclusion criteria were established to filter out irrelevant scientific papers and reports. The relevant articles were closely scrutinized and appraised to extract the required information and data for the possible development of a sustainable roadmap. The search process yielded a number of research articles which were utilized in the systematic review. Two types of models emerged: management/business and science/mathematical models. Although the management/business models explored actions to achieve sustainable growth in the industrial enterprise, science/mathematical models attempted to explain the sustainable behaviors and properties aiming at predominantly ecosystem management. As such, there are major disconnects between the science/mathematical and management/business models in terms of aims and goals. Therefore, there is an urgent need to integrate science and business models of sustainability for the industrial enterprises at large and environmentally challenging industrial sectors in particular. In this paper, we offered examples of practices and concepts which can be used in charting a path towards sustainable development for secondary lead smelters particularly that the waste generated is much greater outside the industrial enterprise than inside. An environmentally-challenging industry such as secondary lead smelters requires a fresh look to chart a path towards sustainable development (i.e., survivability and purposive needs) for all stakeholders (i.e., industrial enterprise, individual stakeholders, and social/ecological systems). Such a path should deal with issues beyond pollution prevention, product stewardship and clean technologies. PMID- 20580989 TI - Reactive oxygen species-mitochondria pathway involved in LYG-202-induced apoptosis in human hepatocellular carcinoma HepG(2) cells. AB - Previously, we demonstrated that LYG-202, a newly synthesized flavonoid with a piperazine substitution, exhibited obvious antitumor activity in vivo and in vitro. The exact mechanism of this new compound remains unclear. In the present study, we examined the effects of LYG-202 on reactive oxygen species (ROS) production and the downstream signaling pathway in the apoptosis of human hepatocellular carcinoma HepG(2) cells. Pretreatment with NAC (N-acetylcysteine), a ROS production inhibitor, partly inhibited the apoptosis induced by LYG-202 via blocking the ROS generation. Further data revealed that LYG-202 induced ROS accumulation followed by a decrease in mitochondrial membrane potential (MMP), release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) to cytosol, which induced apoptosis of the cells. Moreover, the mitogen-activated protein kinases (MAPK), the downstream effect of ROS accumulation including c-Jun N terminal kinase (JNK) and p38 MAPK, could be activated by LYG-202. Taken together, the generation of ROS might play an important role in LYG-202-induced mitochondrial apoptosis pathway, which provided further support for LYG-202 as a novel anticancer therapeutic candidate. PMID- 20580990 TI - Antimicrobial activity of soy edible films incorporated with thyme and oregano essential oils on fresh ground beef patties. AB - Antibacterial activity of soy protein edible films (SPEF) incorporated with 1, 2, 3, 4 and 5% oregano (OR) or thyme (TH) essential oils was evaluated against Escherichia coli, E. coli O157:H7, Staphylococcus aureus, Pseudomonas aeruginosa and Lactobacillus plantarum by the inhibition zone test. Effects of SPEF containing 5% OR and TH or a mixture of OR+TH (ORT) were also tested on fresh ground beef during refrigerated storage (at 4 degrees C). OR and TH incorporated SPEF exhibited similar antibacterial activity against all bacteria in inhibition zone test. While E. coli, E. coli O157:H7 and S. aureus were significantly inhibited by antimicrobial films, L. plantarum and P. aeruginosa appeared to be the more resistant bacteria. SPEF with OR, ORT, and TH did not have significant effects on total viable counts, lactic acid bacteria and Staphylococcus spp. when applied on ground beef patties whereas reductions (p<0.05) in coliform and Pseudomonas spp. counts were observed. PMID- 20580991 TI - Healthier meat products as functional foods. AB - A promising approach to improving health care would be to produce a healthier food supply as a preventive health care strategy. The food supply could be improved by producing functional foods that have nutritional profiles that are healthier than conventional products. However, production of functional foods is not always easily accomplished since they must also taste good, be convenient and reasonably priced so that consumers will regularly purchase and use the products. Meats have great potential for delivering important nutrients such as fatty acids, minerals, dietary fiber, antioxidants and bioactive peptides into the diet. However, to produce successful products with these ingredients, technologies must be developed to increase their stability and decrease their flavor impact on muscle foods. In addition, many regulatory hurdles must be overcome for the commercial production of meats with added nutrients. These include redefinition of standard of identities and policies that allow front of the package nutritional claims. Without these regulatory changes, production of healthier meat products won't become a reality since these products would not have a competitive advantage over unfortified meats. PMID- 20580992 TI - Extra-axial hemangioma VS prenatal brain tumor: Can be differentiated by good ultrasound interpretation. PMID- 20580993 TI - Development of the European Organisation for Research and Treatment of Cancer quality of life questionnaire module for older people with cancer: The EORTC QLQ ELD15. AB - BACKGROUND AND AIM: There is a lack of instruments that focus on the specific health-related quality of life (HRQOL) issues that affect older people with cancer. The aim of this study was to develop a HRQOL questionnaire module to supplement the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire, the EORTC QLQ-C30 for older (>70years) patients with cancer. METHODS: Phases 1-3 were conducted in seven countries following modified EORTC Quality of Life Group guidelines for module development. Phase 1: potentially relevant issues were identified by a systematic literature review, a questionnaire survey of 17 multi-disciplinary health professionals and two rounds of qualitative interviews. The first round included 9 patients aged >70. The second round was a comparative series of interviews with 49 patients >70years with a range of cancer diagnoses and 40 patients aged 50-69years matched for gender and disease site. In Phase 2 the issues were formulated into a long provisional item list. This was administered in Phase 3 together with the QLQ-C30 to two further groups of cancer patients aged >70 (n=97) or 50-69years (n=85) to determine the importance, relevance and acceptability of each item. Redundant and duplicate items were removed; issues specific to the older group were selected for the final questionnaire. RESULTS: In Phase 1, 75 issues were identified. These were reduced in Phase 2 to create a 45 item provisional list. Phase 3 testing of the provisional list led to the selection of 15 items with good range of response, high scores of importance and relevance in the older patients. This resulted in the EORTC QLQ-ELD15, containing five conceptually coherent scales (functional independence, relationships with family and friends, worries about the future, autonomy and burden of illness). CONCLUSION: The EORTC QLQ-ELD15 in combination with the EORTC QLQ-C30 is ready for large-scale validation studies, and will assess HRQOL issues of most relevance and concern for older people with cancer across a wide range of cancer sites and treatment stages. PMID- 20580995 TI - Clinical profile and HLA-DRB1 genotype of late onset multiple sclerosis in Western Australia. AB - We aimed to characterize the clinical profile and human leukocyte antigen (HLA) DRB1 genotype of patients with late onset multiple sclerosis (LOMS) in Western Australia. The clinical features, laboratory studies and HLA-DRB1 alleles were analysed in patients with multiple sclerosis (MS) with onset over 50years of age and compared with 100 patients with early onset MS (EOMS). Of a cohort of 829 patients with MS, 73 (8.8%) presented at over 50years of age, including 14 (1.7%) over 60years. Patients with LOMS had a lower female to male ratio, more frequent initial motor dysfunction, less frequent sensory symptoms and optic neuritis, a more frequent primary-progressive course and shorter time to reach Extended Disability Status Scale (EDSS) scores of 3.0 and 6.0. More LOMS patients were initially misdiagnosed compared to patients with EOMS. HLA-DRB1 *1501 was strongly associated with both LOMS and EOMS compared to the Control subjects, while HLA-DRB1 *0801 was over-represented in patients with LOMS. We concluded that patients with LOMS have a different clinical profile when compared to those with EOMS. Carriers of HLA-DRB1 *0801 may be more prone to develop MS at a later age. PMID- 20580994 TI - The UGT1A1*28 polymorphism correlates with erlotinib's effect on SN-38 glucuronidation. AB - The combination of irinotecan and erlotinib has been evaluated in clinical trials, although toxicity has been significant. We aimed to investigate the effect of erlotinib on SN-38 glucuronidation and the association between UGT1A polymorphisms and SN-38 glucuronidation activity in the presence of erlotinib. The inhibitory effect of erlotinib on SN-38 glucuronidation was determined by measuring the formation rates for SN-38 glucuronide, using recombinant human UGT1A1, pooled human liver microsomes (HLMs) and 52 Caucasian liver microsomes in the absence or presence of erlotinib. Inhibition kinetic studies were conducted. AUC ratios were used to predict the risk of potential drug-drug interactions (DDI) in vivo. Our data showed that erlotinib exhibited potent non-competitive inhibition against SN-38 glucuronidation in pooled HLMs and UGT1A1. Using the physiological and pharmacokinetic parameters obtained from the literature, we estimated the in vivo concentrations of unbound erlotinib available for UGT1A1 active site and thus the AUC ratios of SN-38 were also quantitatively predicted. It is estimated that erlotinib administered at 50mg/day or higher doses may result in at least a 24% increase in SN-38 AUC. Significant correlations were observed between SN-38 glucuronidation activity in the presence of erlotinib and UGT1A1*28 in 52 Caucasian liver microsomes. Our results suggest that erlotinib is a potent inhibitor of SN-38 glucuronidation via UGT1A1 inhibition. The coadministration of erlotinib with irinotecan may result in clinically significant DDI. UGT1A1*28 polymorphism correlates with erlotinib's effect on SN 38 glucuronidation. The present findings shed light on the development and optimisation of combinations involving irinotecan and erlotinib. PMID- 20580996 TI - Interval, acute onset airway obstruction associated with a fracture of the C4 vertebra in a patient with ankylosing spondylitis. AB - We report a 92-year-old female with ankylosing spondylitis who suffered a non displaced cervical fracture of the C4 vertebral body as the result of a mechanical fall. A rigid cervical collar was used to maintain stability. The patient later went on to develop upper airway obstruction as a result of fracture displacement. She was emergently intubated for airway protection. To our knowledge, this is the first report of interval, acute onset upper airway obstruction caused by cervical instability following trauma and fracture in a patient with ankylosing spondylitis. This example highlights one of the potential complications of rigid cervical collar immobilization in patients with spinal instability. PMID- 20580997 TI - The influence of preoperative anticoagulation on outcome and quality of life after surgical treatment of chronic subdural hematoma. AB - The main aim of this study was to investigate the influence of perioperative anticoagulation on the clinical course and outcome of 144 patients who underwent surgery for chronic subdural hematoma (CSDH). The outcome was categorized according to the modified Rankin Scale (mRS), Barthel Index and postoperative quality of life (QoL) scale. There was a significant correlation between preoperative aspirin medication and reoperation (Mann-Whitney U-test, p<0.05). Moreover, dosage and duration of postoperative low-molecular-weight heparin (LMWH) administration were associated with a higher risk of reoperation (Mann Whitney U-test, p<0.01) and a worse outcome on the mRS (Mann-Whitney U-test, p<0.05). Intraoperative treatment with prothrombin complex concentrate led to a poor outcome on the mRS (Craddock-Flood test, p<0.05). Reoperation is the strongest predictive factor of a poor QoL after surgical treatment of CSDH. Both preoperative and postoperative anticoagulation treatment may affect reoperation rate and, thus, postoperative QoL. PMID- 20580998 TI - Cancer stem cells and telomerase as potential biomarkers in veterinary oncology. AB - Despite advances in chemotherapy and radiotherapy, cancer remains a disease of high morbidity and mortality in domestic animals. In parallel to the development of novel therapeutic interventions, appropriate biomarkers are required to detect early-stage disease and disease remission and relapse at both gross and molecular levels, and the effectiveness of therapy. The field of cancer pathogenesis has grown exponentially over the last decade, both in terms of our understanding of the underlying molecular events, and the technologies available to interrogate the cancer cell. This paper reviews the role of the telomerase enzyme and of telomere length as potential biomarkers in cancer. Furthermore, the potential role of cancer stem cells as biomarkers of malignancy and disease progression is assessed. PMID- 20580999 TI - Body size, IGF and growth hormone polymorphisms, and colorectal adenomas and hyperplastic polyps. AB - OBJECTIVE: We examined the risk of colorectal polyps in relation to body size factors and candidate polymorphisms in selected genes of insulin-like growth factor (IGF1) (rs5742612), IGF1 receptor (IGF1R) (rs2229765), IGF binding protein 3 (IGFBP3) (rs2854746) and growth hormone (GH1) (rs2665802). DESIGN: Cases with colorectal adenomas (n=519), hyperplastic polyps (n=691), or both lesions (n=227), and controls (n=772), aged 20-74 years, were recruited from patients who underwent colonoscopy between December 2004 and September 2007 at a large integrated-health plan in Washington state. Subjects participated in a 45-minute telephone interview to ascertain body size and physical activity, and provided a buccal DNA sample for genetic analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable polytomous regression. RESULTS: Compared to those of normal weight, higher body mass index (BMI) was associated with elevated risk of colorectal adenomas (OR=1.65, 95% CI 1.22-2.25 BMI>or=30 kg/m(2), p-trend=0.002) and both lesions (OR=2.15, 95% CI 1.43-3.22 BMI>or=30 kg/m(2), p-trend=0.003), but there was no relationship with hyperplastic polyps. Obesity at age 18 and a weight gain of >or=21 kg since age 18 were also significantly associated with an increased risk of colorectal adenomas and both lesions, but not hyperplastic polyps. There was a reduced risk of colorectal adenomas (OR=0.63, 95% CI 0.42-0.94) and hyperplastic polyps (OR=0.7, 95% CI 0.5-0.9) associated with the homozygous variant genotype for GH1. Few meaningful results were evident for the other polymorphisms. CONCLUSIONS: There is an increased risk of colorectal adenomas and presence of both adenomas and hyperplastic polyps in relation to increasing body size. Some genetic variation in GH1 might contribute to a reduced risk of colorectal adenomas and hyperplastic polyps. PMID- 20581000 TI - [Image guided radiation therapy (IGRT)]. AB - Image guided radiation therapy (IGRT) is a major technical innovation of radiotherapy. It allows locating the tumor under the linear accelerator just before the irradiation, by direct visualization (3D mode soft tissue) or indirect visualization (2D mode and radio-opaque markers). The technical implementation of IGRT is done by very different complex devices. The most common modality, because available in any new accelerator, is the cone beam CT. The main experiment of IGRT focuses on prostate cancer. Preliminary studies suggest the use of IGRT combined with IMRT should increase local control and decrease toxicity, especially rectal toxicity. In head and neck tumors, due to major deformation, a rigid registration is insufficient and replanning is necessary (adaptive radiotherapy). The onboard imaging delivers a specific dose, needed to be measured and taken into account, in order not to increase the risk of toxicity. Studies comparing different modalities of IGRT according to clinical and economic endpoints are ongoing; to better define the therapeutic indications. PMID- 20581002 TI - Contrast-enhanced ultrasonography of the prostate with Sonazoid. AB - OBJECTIVE: The diagnosis of prostate cancer is based on the results of ultrasonography-guided needle biopsy of the prostate, but cancer foci are often not visible in conventional transrectal ultrasonography. Sonazoid is a new microbubble contrast agent. The purpose of our study was to compare areas of contrast material enhancement in the prostate at ultrasonography with whole-mount radical prostatectomy specimens to determine if the use of Sonazoid improves the detection rate of prostate cancer. METHODS: Fifty patients with biopsy-proven cancer of the prostate who were scheduled to undergo radical prostatectomy were recruited for this study. The day before the operation, each patient was evaluated with ultrasonography at baseline and again during intravenous infusion of Sonazoid. A map of ultrasonography findings was created prospectively at the time of imaging. Following radical prostatectomy, independent mapping of the pathologic results was performed and the maps were compared. RESULTS: Ultrasonography evaluation at baseline demonstrated that at least one focus of cancer was identified in 20 of the 50 subjects (40.0%). Meanwhile at least one cancer focus was enhanced in 31 of the 50 patients (62.0%) when Sonazoid was used. The combination of baseline grayscale imaging and contrast-enhanced imaging allowed identification of at least one focus of cancer in 40 patients (80.0%). Contrast-enhanced ultrasonography can improve sensitivity, especially for the detection of large cancer, peripheral zone cancer and highly malignant cancer. CONCLUSIONS: Our study has demonstrated significantly improved detection of prostate cancer with the combination of baseline grayscale imaging and contrast enhanced imaging compared with conventional ultrasonography techniques only, and this technique may be applicable to targeted biopsy. PMID- 20581001 TI - Effectiveness of web-based interventions on patient empowerment: a systematic review and meta-analysis. AB - BACKGROUND: Patient empowerment is growing in popularity and application. Due to the increasing possibilities of the Internet and eHealth, many initiatives that are aimed at empowering patients are delivered online. OBJECTIVE: Our objective was to evaluate whether Web-based interventions are effective in increasing patient empowerment compared with usual care or face-to-face interventions. METHODS: We performed a systematic review by searching the MEDLINE, EMBASE, and PsycINFO databases from January 1985 to January 2009 for relevant citations. From the 7096 unique citations retrieved from the search strategy, we included 14 randomized controlled trials (RCTs) that met all inclusion criteria. Pairs of review authors assessed the methodological quality of the obtained studies using the Downs and Black checklist. A meta-analysis was performed on studies that measured comparable outcomes. The GRADE approach was used to determine the level of evidence for each outcome. RESULTS: In comparison with usual care or no care, Web-based interventions had a significant positive effect on empowerment measured with the Diabetes Empowerment Scale (2 studies, standardized mean difference [SMD] = 0.61, 95% confidence interval [CI] 0.29 - 0.94]), on self-efficacy measured with disease-specific self-efficacy scales (9 studies, SMD = 0.23, 95% CI 0.12 - 0.33), and on mastery measured with the Pearlin Mastery Scale (1 study, mean difference [MD] = 2.95, 95% CI 1.66 - 4.24). No effects were found for self efficacy measured with general self-efficacy scales (3 studies, SMD = 0.05, 95% CI -0.25 to 0.35) or for self-esteem measured with the Rosenberg Self-Esteem Scale (1 study, MD = -0.38, 95% CI -2.45 to 1.69). Furthermore, when comparing Web-based interventions with face-to-face deliveries of the same interventions, no significant (beneficial or harmful) effects were found for mastery (1 study, MD = 1.20, 95% CI -1.73 to 4.13) and self-esteem (1 study, MD = -0.10, 95% CI 0.45 to 0.25). CONCLUSIONS: Web-based interventions showed positive effects on empowerment measured with the Diabetes Empowerment Scale, disease-specific self efficacy scales and the Pearlin Mastery Scale. Because of the low quality of evidence we found, the results should be interpreted with caution. The clinical relevance of the findings can be questioned because the significant effects we found were, in general, small. PMID- 20581003 TI - Indications for ureteropyeloscopy based on radiographic findings and urine cytology in detection of upper urinary tract carcinoma. AB - OBJECTIVE: To verify the indication of diagnostic ureteropyeloscopy based on clinical features for upper urinary tract urothelial cancer with over 100 patients and over a 10-year series. METHODS: From January 1997 to December 2008, consecutive 129 units in 124 patients underwent ureteropyeloscopy to obtain a definitive diagnosis of upper urinary tract cancer or to rule out a malignancy. Patients were divided into four subgroups based on voided urine cytology and preoperative radiographic findings: group A (n = 8), positive urine cytology and positive radiographic findings; group B (n = 4), positive cytology and negative radiographic findings; group C (n = 55), negative cytology and positive radiographic findings and group D (n = 62), gross hematuria originating from the upper urinary tract with negative cytology and negative radiographic findings. Ureteropyeloscopic findings were compared with radiographic and cytological results. Adverse effects were also investigated. RESULTS: In group A, all patients had confirmed cancer. In group B, one revealed small cancer and the remaining three confirmed carcinoma in situ by biopsy with ureteropyeloscopy. In groups C and D, 33 patients (60%) and four (6.5%) revealed cancer. Seventy-eight patients out of 80 (97.5%) in groups C and D were confirmed to have benign disease. No patient was found with malignancy during follow up after negative finding of ureteropyeloscopy. CONCLUSIONS: Ureteropyeloscopy can help in detecting upper urinary tract cancer or to rule out malignancy for patients with negative voiding cytology. However, ureteropyeloscopy is redundant for patients with positive radiographic findings and positive voiding cytology. PMID- 20581004 TI - Impact of competitive flow on wall shear stress in coronary surgery: computational fluid dynamics of a LIMA-LAD model. AB - AIMS: Competitive flow from native coronary vessels is considered a major factor in the failure of coronary bypass grafts. However, the pathophysiological effects are not fully understood. Low and oscillatory wall shear stress (WSS) is known to induce endothelial dysfunction and vascular disease, like atherosclerosis and intimal hyperplasia. The aim was to investigate the impact of competitive flow on WSS in mammary artery bypass grafts. METHODS AND RESULTS: Using computational fluid dynamics, WSS was calculated in a left internal mammary artery (LIMA) graft to the left anterior descending artery in a three-dimensional in vivo porcine coronary artery bypass graft model. The following conditions were investigated: high competitive flow (non-significant coronary lesion), partial competitive flow (significant coronary lesion), and no competitive flow (totally occluded coronary vessel). Time-averaged WSS of LIMA at high, partial, and no competitive flow were 0.3-0.6, 0.6-3.0, and 0.9-3.0 Pa, respectively. Further, oscillatory WSS quantified as the oscillatory shear index (OSI) ranged from (maximum OSI = 0.5 equals zero net WSS) 0.15 to 0.35, <0.05, and <0.05, respectively. Thus, high competitive flow resulted in substantial oscillatory and low WSS. Moderate competitive flow resulted in WSS and OSI similar to the no competitive flow condition. CONCLUSION: Graft flow is highly dependent on the degree of competitive flow. High competitive flow was found to produce unfavourable WSS consistent with endothelial dysfunction and subsequent graft narrowing and failure. Partial competitive flow, however, may be better tolerated as it was found to be similar to the ideal condition of no competitive flow. PMID- 20581006 TI - The Escherichia coli glycophage display system. AB - We describe a phage display technique that allows the production and selective enrichment of phages that display an N-glycoprotein (glycophages). We applied glycophage display to select functional glycosylation sequons from a pool of randomized acceptor sequences. Our system provides a genetic platform to study and engineer different steps in the pathway of bacterial N-linked protein glycosylation. PMID- 20581005 TI - Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. AB - AIMS: The density of vasa vasorum within atherosclerotic plaque correlates with histologic features of plaque vulnerability in post-mortem studies. Imaging methods to non-invasively detect vasa vasorum are limited. We hypothesized that contrast ultrasound (CUS) can quantify vasa vasorum during atherosclerosis progression. METHODS AND RESULTS: New Zealand white rabbits received a high-fat diet for 3 weeks, and bilateral femoral artery stenosis was induced by balloon injury. Contrast ultrasound femoral imaging was performed at baseline and 2, 4, and 6 weeks post injury to quantify adventitial videointensity. At each imaging time point 10 vessels were sectioned and stained with haematoxylin and eosin and von-Willebrand factor. Adventitial vasa vasorum density was quantified by counting the number of stained microvessels and their total cross-sectional area. Plaque size (per cent lumen area) progressed over time (P < 0.001), as did adventitial vasa vasorum density (P < 0.001). Plateau peak videointensity also progressed, demonstrating a strong linear correlation with histologic vasa vasorum density (P < 0.001). Receiver operating characteristic analysis indicated that a three-fold increase in median adventitial videointensity had a sensitivity of 100% and specificity of 88% for predicting abnormal neovascularization. CONCLUSION: We have histologically validated that CUS quantifies the development of adventitial vasa vasorum associated with atherosclerosis progression. This imaging technique has the potential for characterizing prognostically significant plaque features. PMID- 20581007 TI - C-Mannosylated peptides derived from the thrombospondin type 1 repeat interact with Hsc70 to modulate its signaling in RAW264.7 cells. AB - The thrombospondin type 1 repeat (TSR) is a functional module of proteins called TSR superfamily proteins (e.g., thrombospondin, F-spondin, mindin, etc.) and includes a conserved Trp-x-x-Trp (W-x-x-W) motif, in which the first Trp residue is preferably modified by C-mannosylation. We previously reported that synthesized C-mannosylated TSR-derived peptides (e.g., C-Man-WSPW) specifically enhanced lipopolysaccharide-induced signaling in macrophage-like RAW264.7 cells. In this study, we searched for the proteins that bind to C-mannosylated TSR derived peptides in RAW264.7 cells and identified heat shock cognate protein 70 (Hsc70). The binding affinity of Hsc70 for C-mannosylated peptides in solution was higher than that for the peptides without C-mannose. The binding was influenced by a nucleotide-induced conformational change of Hsc70, and C mannosylated peptides preferred the substrate-binding domain of Hsc70. Furthermore, in RAW264.7 cells, addition of Hsc70 stimulated cellular signaling to produce tumor necrosis factor-alpha, via transforming growth factor-beta activated kinase 1, and the Hsc70-induced signaling was enhanced more in the presence of the peptides with C-mannose than that without C-mannose, suggesting functional interaction between Hsc70 and the C-mannosylated peptides in the cells. Together, these results demonstrate a novel function of the C mannosylation of TSR-derived peptides in terms of interaction with Hsc70 to regulate cellular signaling. PMID- 20581009 TI - Characterization and binding activity of the chondroitin/dermatan sulfate chain from Endocan, a soluble endothelial proteoglycan. AB - Endocan is a recently identified soluble chondroitin/dermatan sulfate (CS/DS) proteoglycan. Synthesized by endothelial cells, it has been found to be over expressed in the vasculature surrounding a number of tumors, and by promoting growth factor mitogenic activities, hepatocyte growth factor/scatter factor (HGF/SF) in particular, it supports cellular proliferation. In this work, we characterized the glycosaminoglycan (GAG) chain of Endocan, purified either from the naturally producing human umbilical vein endothelial cells (HUVEC) or from a recombinant over-expression system in human embryonic kidney cells (HEK). Compositional analysis using different chondroitinases as well as nuclear magnetic resonance studies revealed that the GAG chains from both sources share many characteristics, with the exception of size (15 and 40 kDa, respectively, for HUVEC and HEK-293 cells). The DS-specific, IdoA-containing disaccharides contribute 30% of the chain (15% of which are 2-O-sulfated) and are mostly clustered in tetra- (35%), hexa- (12%), and octa- (5%) saccharide domains. Highly sulfated D, E, and B disaccharide units (HexA2S-GalNAc6S, HexA-GalNAc4S6S, and HexA2S-GalNAc4S) were also detected in significant amounts in both chains and may account for the HGF/SF-binding activity of the CS/DS. This work establishes that HEK-293 cells can be engineered to provide a valuable source of Endocan with authentic CS/DS chains, enabling the purification of sufficient amounts for structural and/or binding analysis and providing a possible model of Endocan CS/DS chain organization. PMID- 20581008 TI - Levels of specific glycans significantly distinguish lymph node-positive from lymph node-negative breast cancer patients. AB - One of the most urgent requirements in breast cancer is the development of a blood-based test for early detection and prognosis. Previously published results found a significant difference between specific glycan levels in patients with advanced breast cancer and healthy controls. The aim of this investigation was to address a more clinically relevant problem, i.e., whether the measurement of specific glycans could identify women with aggressive disease at an early stage. In order to reduce potential bias in this study, blood samples from patients were collected, stored and analyzed in a similar manner. Agalactosyl biantennary glycans (FA2) and glycans containing the sialyl Lewis x epitope (A3F1G1 and A2F1G1) were measured using high throughput normal-phase high-performance liquid chromatography in combination with exoglycosidase digestions in sera from 52 patients with early breast cancer (21 with lymph node-negative and 20 with lymph node-positive disease) and 134 women with benign breast disease. The combined levels of the glycans were significantly higher in patients with lymph node metastases compared to women without these metastases. Lymph node status is the single most important determinant of survival in early stage breast cancer. As high levels of these glycans were associated with nodal metastases, their measurement may provide a new non-invasive approach to determining prognosis in women with newly diagnosed breast cancer. PMID- 20581010 TI - Cooperation of beta-galactosidase and beta-N-acetylhexosaminidase from bifidobacteria in assimilation of human milk oligosaccharides with type 2 structure. AB - Bifidobacteria are predominant in the intestines of breast-fed infants and offer health benefits to the host. Human milk oligosaccharides (HMOs) are considered to be one of the most important growth factors for intestinal bifidobacteria. HMOs contain two major structures of core tetrasaccharide: lacto-N-tetraose (Galbeta1 3GlcNAcbeta1-3Galbeta1-4Glc; type 1 chain) and lacto-N-neotetraose (Galbeta1 4GlcNAcbeta1-3Galbeta1-4Glc; type 2 chain). We previously identified the unique metabolic pathway for lacto-N-tetraose in Bifidobacterium bifidum. Here, we clarified the degradation pathway for lacto-N-neotetraose in the same bifidobacteria. We cloned one beta-galactosidase (BbgIII) and two beta-N acetylhexosaminidases (BbhI and BbhII), all of which are extracellular membrane bound enzymes. The recombinant BbgIII hydrolyzed lacto-N-neotetraose into Gal and lacto-N-triose II, and furthermore the recombinant BbhI, but not BbhII, catalyzed the hydrolysis of lacto-N-triose II to GlcNAc and lactose. Since BbgIII and BbhI were highly specific for lacto-N-neotetraose and lacto-N-triose II, respectively, they may play essential roles in degrading the type 2 oligosaccharides in HMOs. PMID- 20581011 TI - Evolution of tree nutrition. AB - Using a broad definition of trees, the evolutionary origins of trees in a nutritional context is considered using data from the fossil record and molecular phylogeny. Trees are first known from the Late Devonian about 380 million years ago, originated polyphyletically at the pteridophyte grade of organization; the earliest gymnosperms were trees, and trees are polyphyletic in the angiosperms. Nutrient transporters, assimilatory pathways, homoiohydry (cuticle, intercellular gas spaces, stomata, endohydric water transport systems including xylem and phloem-like tissue) and arbuscular mycorrhizas preceded the origin of trees. Nutritional innovations that began uniquely in trees were the seed habit and, certainly (but not necessarily uniquely) in trees, ectomycorrhizas, cyanobacterial, actinorhizal and rhizobial (Parasponia, some legumes) diazotrophic symbioses and cluster roots. PMID- 20581012 TI - Seasonal variations of gas exchange and water relations in deciduous and evergreen trees in monsoonal dry forests of Thailand. AB - This study compared leaf gas exchange, leaf hydraulic conductance, twig hydraulic conductivity and leaf osmotic potential at full turgor between two drought deciduous trees, Vitex peduncularis Wall. and Xylia xylocarpa (Roxb.) W. Theob., and two evergreen trees, Hopea ferrea Lanessan and Syzygium cumini (L.) Skeels, at the uppermost canopies in tropical dry forests in Thailand. The aims were to examine (i) whether leaf and twig hydraulic properties differ in relation to leaf phenology and (ii) whether xylem cavitation is a determinant of leaf shedding during the dry season. The variations in almost all hydraulic traits were more dependent on species than on leaf phenology. Evergreen Hopea exhibited the lowest leaf-area-specific twig hydraulic conductivity (leaf-area-specific K(twig)), lamina hydraulic conductance (K(lamina)) and leaf osmotic potential at full turgor (Psi(o)) among species, whereas evergreen Syzygium exhibited the highest leaf-area-specific K(twig), K(lamina) and Psi(o). Deciduous Xylia had the highest sapwood-area-specific K(twig), along with the lowest Huber value (sapwood area/leaf area). More negative osmotic Psi(o) and leaf osmotic adjustment during the dry season were found in deciduous Vitex and evergreen Hopea, accompanied by low sapwood-area-specific K(twig). Regarding seasonal changes in hydraulics, no remarkable decrease in K(lamina) and K(twig) was found during the dry season in any species. Results suggest that leaf shedding during the dry season is not always associated with extensive xylem cavitation. PMID- 20581013 TI - Global climate change and tree nutrition: influence of water availability. AB - The effects of global climate change will regionally be very different, mainly causing considerable changes in temperature and water availability. For Central Europe, for example, increased temperatures are predicted, which will cause increased frequencies and durations of summer drought events. On the other hand, the predicted changes in precipitation patterns will lead to enhanced rainfall during winter and spring, thereby increasing the risk of flooding in Central and Northern Europe. Depending on the sensitivity to reduced water availability on the one hand and oxygen depletion due to waterlogging on the other, physiological performance, growth and competitive ability of trees may be adversely affected. Both drought and excess water availability impair the mineral nutrition of trees by influencing on the one hand the nutrient availability in the soil and on the other hand the physiology of the uptake systems mainly of the mycorrhizal tree roots. Extreme water regimes also change interaction patterns among plants and between plants and microorganisms, and alter the carbon balance of trees and ecosystems. Here we summarize and discuss the present knowledge on tree nutrition under altered water availability as expected to be more common in the future. The focus is on tree mineral nutrient uptake and metabolism as well as on the interaction between carbon allocation and the mineral nutrient balance as affected by reduced and excess water availability. PMID- 20581014 TI - CAST and ELKS proteins: structural and functional determinants of the presynaptic active zone. AB - Cytomatrix at the active zone-associated structural protein (CAST) was first purified from rat brain. It belongs to a protein family with the protein ELKS being its close relative. In nerve terminals, these proteins are specifically localized in the active zone (AZ). They have been shown to directly interact with other AZ proteins, including RIM1, Piccolo and Bassoon, and indirectly with Munc13-1 through RIM1, forming a large molecular complex at AZ. Moreover, the direct interaction of CAST with RIM1 and Bassoon appears to be involved in the release of neurotransmitters. However, it still remains elusive how CAST and ELKS regulate the assembly and function of AZ during synapse maturation. This review focuses on recent findings about the ELKS/CAST family revealed by biochemical strategies and genetic studies, and discusses the potential roles of this protein family in the function and organization of the presynaptic AZ. PMID- 20581015 TI - The relationship between post-onset pregnancy and functional outcome in women with recent onset inflammatory polyarthritis: results from the Norfolk Arthritis Register. AB - OBJECTIVE: To examine the influence of post-symptom-onset pregnancy on disease outcome in women with inflammatory polyarthritis (IP). METHODS: A total of 631 women, aged <48 years at symptom onset, were registered with the Norfolk Arthritis Register (NOAR) between 1990 and 2004. Functional disability was assessed using the Stanford Health Assessment Questionnaire (HAQ). Blood was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). The date and outcome of all pregnancies were reported during a median follow-up of 7 years. Linear random effects models were used to examine HAQ score over time, by pregnancy status. RESULTS: were then stratified for RF and ACPA status. Results In all, 72 women had a post-onset pregnancy (Po-P) including 45 women who were pregnant at a follow-up assessment. Pregnancy was generally associated with lower HAQ scores over time than non-pregnancy. The 10 ACPA positive women who had a Po-P had significantly worse subsequent HAQ scores. CONCLUSION: Overall, Po-P is associated with lower HAQ scores, compared to no Po P. This may reflect a beneficial effect of pregnancy on disease outcome, or that predominantly women with milder disease become pregnant. In women with the worst predicted outcome (APCA positive), Po-P is associated with a worse outcome than no pregnancy. PMID- 20581016 TI - B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy. AB - OBJECTIVES: To examine the expression of B-cell-activating factor receptor (BAFF R) on naive CD27- and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab. PATIENTS AND METHODS: BAFF-R expression on B-cell subsets was determined in normal controls (NC; n = 11), active patients with RA pre-rituximab (pre-RX; n = 15), relapsing patients either concordant for B-cell repopulation (C R, n = 13) or discordant, with relapse more than 3 months after repopulation (D R, n = 11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n = 5). Serum BAFF was measured by ELISA and analysed using Mann-Whitney. RESULTS: There was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p < 0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p < 0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p < 0.05). CONCLUSION: BAFF R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA. PMID- 20581017 TI - Cardiovascular risk factors in primary Sjogren's syndrome: a case-control study in 624 patients. AB - We evaluated the prevalence and clinical significance of cardiovascular risk factors in a large series of patients with primary Sjogren's syndrome (SS), focusing on the possible association with clinical and immunological SS features, the therapies administered, and the impact on cardiovascular disease. The study cohort included 312 patients fulfilling the 2002 classification criteria for primary SS, consecutively evaluated and followed in our department between 1984 and 2009. The control group consisted of 312 age- and sex-matched patients without systemic autoimmune diseases followed during the study period in a primary care centre. In comparison with the age- and sex-matched control group, patients with primary SS showed a higher frequency of diabetes mellitus (27% versus 13%, p < 0.001) and hypertriglyceridaemia (22% versus 15%, p = 0.023), and a lower frequency of hypertension (30% versus 46%, p < 0.001) and smoking (19% versus 31%, p < 0.001). The adjusted, multivariate analysis showed that SS patients with at least three cardiovascular risk factors had a higher mean age at SS diagnosis (p < 0.001), a higher frequency of liver involvement (p = 0.01) and central nervous system involvement (p = 0.001), higher mean levels of C-reactive protein (CRP, p = 0.001), a lower percentage of circulating gamma globulins (p = 0.001), and had received corticosteroids more frequently (p = 0.003) in comparison with patients without cardiovascular risk factors. Patients who had received corticosteroids showed a higher frequency of hypertension (37% versus 25%, p = 0.032), diabetes mellitus (37% versus 21%, p = 0.002), and hypertriglyceridaemia (33% versus 15%, p < 0.001). Patients with primary SS showed a twofold higher prevalence of diabetes mellitus and a 1.5-fold higher prevalence of hypertriglyceridaemia in comparison with primary care patients. Corticosteroid use was closely associated with cardiovascular risk factors. These results suggest that cardiovascular risk factors should be taken into account in the management of patients with primary SS and show the importance of recognizing and controlling both traditional and SS-related modifiable risk factors. PMID- 20581018 TI - Autoantibodies to double-stranded DNA--intermethod comparison between four commercial immunoassays and a research biosensor-based device. AB - Patients with systemic lupus erythematosus (SLE) often develop a wide variety of serological manifestations including the presence of antibodies to double stranded DNA (anti-dsDNA). Positivity for anti-dsDNA constitutes one of the laboratory criteria for the diagnosis of SLE and is therefore clinically relevant. We analyzed the diagnostic accuracies of four commercial anti-dsDNA immunoassays and compared the results with a recently established surface plasmon resonance (SPR) biosensor chip with covalently chip-immobilized dsDNA. The anti dsDNA measurements were performed retrospectively in 50 patients with clinically proven SLE, 39 patients with other autoimmunopathies and 20 healthy controls. Data were evaluated by Receiver-Operator Characteristic (ROC) analysis, with special regard to SLE patients suffering from lupus nephritis. The ROC analyses for the four immunoassays and the SPR biosensor resulted in the following area under-the-curve (AUC) and diagnostic efficiency (DE) values in descending order: Bindazyme AUC, 0.89; DE, 0.88; ELiA AUC, 0.89; DE, 0.86; SPR biosensor AUC, 0.82; DE, 0.80; Farrzyme AUC, 0.77; DE, 0.77; Farr AUC, 0.77; DE, 0.70. When considering the 22 nephritis SLE patients the following AUC were observed: Bindazyme 0.98; EliA 0.95; SPR biosensor 0.93; Farr 0.89; Farrzyme 0.88. Although various methodologies for the determination of anti-dsDNA were compared, the overall diagnostic accuracy was found satisfactory in all immunoassays. Best data were found for the Bindazyme assay. We referenced the measurements to our in house SPR biosensor device which showed good AUC and DE values. When optimized, this technique, allowing to monitor antigen/ antibody interactions in real-time, may add a new analytical quality to the existing methods, potentially beneficial in diagnosis and clinical monitoring of SLE. PMID- 20581019 TI - Good outcomes with mycophenolate-cyclosporine-based induction protocol in children with severe proliferative lupus nephritis. AB - The outcomes of children with severe proliferative lupus nephritis (LN) were examined using a new mycophenolate and cyclosporine-based (MMF-CSA) induction protocol. Sixteen children with LN (WHO class III and IV), 31.3% of whom required dialysis at induction, were retrospectively studied. Median MMF dose was 942 mg/m( 2)/day. Thirteen patients (81%) with persistent proteinuria received CSA. Clinical and laboratory parameters were compared at pre-induction, 6 and 12 months. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, haematuria, proteinuria and serological markers (complements C3, C4 and anti-dsDNA). Comparing these parameters at induction, 6 months and 12 months, respectively, SLEDAI (25.4 +/- 8.7 versus 3.2 +/- 2.9 versus 2.9 +/- 2.8), serum C3 (47 +/- 21 versus 107 +/- 27 versus 111 +/- 38 mg/dl), C4 (12 +/- 14 versus 23 +/- 14 versus 22 +/- 11 mg/dl) and urine protein (6.97 +/- 7.09 versus 0.98 +/- 1.56 versus 0.21 +/- 0.13 g/ day/1. 73 m(2)) improved significantly (p < 0.05). Anti-dsDNA titres decreased in 73% by 6 and 12 months (p < 0.05). Complete renal remission was achieved in 7/16 (43.8%) at 6 months and 12/16 (75%) at 12 months, the rest achieving partial remission with no treatment failures. In conclusion, a combination MMF-CSA protocol is an effective therapeutic alternative for induction of children with severe proliferative LN, resulting in significant clinical and serological improvement with minimal adverse effects. PMID- 20581020 TI - Tacrolimus is an alternative therapeutic option for the treatment of refractory lupus nephritis. AB - We conducted an open-labeled, prospective study to determine the efficacy and safety of tacrolimus as an alternative therapeutic option for those patients with refractory lupus nephritis. The study population comprised one male and eight female patients with diffuse proliferative lupus nephritis. All patients had failed to respond to sufficient intravenous cyclophosphamide therapy with proteinuria of >or=1 g/day and active urinary sediments. Tacrolimus (0.1 mg/kg/day) was administered for 1 year with adjusting drug level (4-10 microg/l). The mean serum creatinine level and spot urine protein creatinine ratio (UPCR) at baseline were 1.39 mg/dl and 2.27, respectively. After the treatment, proteinuria reduced significantly from median UPCR value of 2.19 (range, 1.19-3.34) to 0.44 (range, 0.12-2.13) (p < 0.05). Seven (78%) of the nine patients showed a complete clinical response, which was defined as stabilization in the disease-activity markers and serum creatinine level with reduction of >or=50% in UPCR; two patients showed complete remission with UPCR <0.2. One patient showed treatment failure because of the disease progression. No serious adverse effects were observed during the study. This study demonstrates that tacrolimus can show a significant therapeutic response in cases that are refractory to the standard regimen for diffuse proliferative lupus nephritis. PMID- 20581021 TI - Chemosis as a presenting symptom of systemic lupus erythematosus. AB - We present a case of chemosis (conjunctival edema) as an early manifestation of severe systemic lupus erythematosus affecting multiple organs, including the central nervous system and the kidneys. PMID- 20581022 TI - On Kikuchi's disease and lupus. PMID- 20581023 TI - Severe ischemia following treatment with rituximab in a patient with mixed connective tissue disease: an unusual complication. PMID- 20581024 TI - Responsibilities of the editor. PMID- 20581025 TI - Mini extracorporeal circuit cardiopulmonary bypass system: a review. AB - Improved knowledge of the pathophysiological processes experienced in response to cardiopulmonary bypass has led to new developments in extracorporeal technology and understanding. The use of mini extracorporeal circuits (MECC) is rapidly expanding in clinical practice. The mini extracorporeal circuit differs by a greatly reduced tubing length and the number of components when compared with current circuit designs. The MECC is believed to offer potential benefits to the surgical patient by reducing the systemic inflammatory response that remains strongly implicated in post-operative organ dysfunction. We present a review of the available literature and find the MECC to show an acceptable safety profile with a reduction in post-operative complications and transfusion requirements and no evidence of any negative impairment to the surgeon, anaesthetist or perfusionist. The observed post-bypass inflammatory response is seen to be lower after MECC bypass and this is of clear clinical benefit. PMID- 20581028 TI - Pathophysiological aspects of cardiotomy suction usage. AB - Cardiotomy suction is used for preservation of autologous blood during on-pump cardiac surgery at present. Controversially, the exclusion of cardiotomy suction in some types of operations (coronary artery bypass surgery) is not necessarily associated with an increased transfusion requirement. On the other hand, the use of cardiotomy suction causes an amplification of systemic inflammatory response and a resulting coagulopathy, as well as exacerbation of the microembolic load and hemolysis. This leads to a tendency towards increased blood loss, transfusion requirement and organ dysfunction. On the basis of these facts, it is appropriate to reconsider routine use of cardiotomy suction in on-pump coronary artery surgery. PMID- 20581029 TI - Surgical treatment of tricuspid valve endocarditis: a single-centre experience. AB - OBJECTIVES: We describe our ten-year experience with surgery for isolated tricuspid valve (TV) infective endocarditis. METHODS: Data were collected through a retrospective patient record review. Between 1999 and 2009, 13 (4.6%) patients had isolated TV surgery. The mean age was 40+/-15 years and there were nine male patients and 4 female patients. Eight (61%) patients were previous intravenous drug users. Indications for surgery included severe TV regurgitation (n=5), uncontrolled infection (n=4), septic pulmonary emboli (n=3) and TV stenosis (n=1). Staphylococcus aureus (n=3) and gram negative organisms (n=2) were isolated pre-operatively. Eleven patients had replacement surgery while two valves were repaired. RESULTS: There were no hospital deaths. Post-operative complications included new atrial fibrillation (n=5), re-operation (n=2), permanent pacemaker (n=2), and renal dialysis (n=1). Five (38%) patients died during the follow-up period. Cause of death was cardiac related in four patients. Actuarial survival was 63.1% at 3 years and 50.4% at 5 years. One patient developed recurrent TV endocarditis. There were no further cases of prosthetic valve failure. TV regurgitation remained trivial in both repaired valves. CONCLUSIONS: Surgery for isolated TV endocarditis is often associated with previous intravenous drug use. The procedure can be performed with acceptable hospital morbidity and no mortality. Late mortality is high, despite the young age of the patients. PMID- 20581030 TI - What can cooperation between Israeli and Palestinian doctors achieve? PMID- 20581031 TI - Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance. PMID- 20581041 TI - Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men. AB - We aimed to determine if any mechanistic differences exist between a single set (1SET) and multiple sets (i.e. 3 sets; 3SET) of resistance exercise by utilizing a primed constant infusion of [ring-13C6]phenylalanine to determine myofibrillar protein synthesis (MPS) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise. Eight resistance-trained men (24+/-5 years, BMI=25+/-4 kg m2) were randomly assigned to perform unilateral leg extension exercise at 70% concentric one repetition maximum (1RM) until volitional fatigue for 1SET or 3SET. Biopsies from the vastus lateralis were taken in the fasted state (Fast) and fed state (Fed; 20 g of whey protein isolate) at rest, 5 h Fed, 24 h Fast and 29 h Fed post-exercise. Fed state MPS was transiently elevated above rest at 5 h for 1SET (2.3-fold) and returned to resting levels by 29 h post-exercise. However, the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h (3.1-fold above rest) and 29 h post-exercise (2.3-fold above rest). Phosphorylation of 70 kDa S6 protein kinase (p70S6K) demonstrated a coordinated increase with MPS at 5 h and 29 h post-exercise such that the extent of p70S6K phosphorylation was related to the MPS response (r=0.338, P=0.033). Phosphorylation of 90 kDa ribosomal S6 protein kinase (p90RSK) and ribosomal protein S6 (rps6) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed, respectively. However, 3SET induced a greater activation of eukaryotic translation initiation factor 2B (eIF2B) and rpS6 at 5 h Fed. These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time. PMID- 20581042 TI - Loss of Kitlow progenitors, reduced stem cell factor and high oxidative stress underlie gastric dysfunction in progeric mice. AB - Gastrointestinal functions decline with ageing leading to impaired quality of life, and increased morbidity and mortality. Neurodegeneration is believed to underlie ageing-associated dysmotilities but the mechanisms have not been fully elucidated. We used progeric mice deficient in the anti-ageing peptide Klotho to investigate the contribution of key cell types of the gastric musculature to ageing-associated changes in stomach function and the underlying mechanisms. Klotho expression, enteric neurons, interstitial cells of Cajal (ICC), smooth muscle cells and electrical activity were assessed by immunofluorescence, confocal microscopy, 3-dimensional reconstruction, flow cytometry, quantitative RT-PCR, Western immunoblotting and intracellular recordings. Gastric emptying of solids was analysed by the [13C]octanoic acid breath test. Circulating and tissue trophic factors were measured by enzyme immunoassays and quantitative RT-PCR. The role of oxidative stress was investigated in organotypic cultures. Klotho expression was detected in gastric glands, myenteric neurons and smooth muscle cells. Progeric Klotho-deficient mice had profound loss of ICC and ICC stem cells without a significant decrease in neuron counts, expression of neuronal nitric oxide synthase or smooth muscle myosin. Slow wave amplitude and nitrergic inhibitory junction potentials were reduced while solid emptying was unchanged. Klotho-deficient mice were marantic and had low insulin, insulin-like growth factor-I and membrane-bound stem cell factor. Klotho deficiency accentuated oxidative stress and ICC loss. We conclude that Klotho-deficient, progeric mice display a gastric phenotype resembling human ageing and involving profound ICC loss. Klotho protects ICC by preserving their precursors, limiting oxidative stress, and maintaining nutritional status and normal levels of trophic factors important for ICC differentiation. PMID- 20581043 TI - Kinetic analysis of the effects of H+ or Ni2+ on Kv1.5 current shows that both ions enhance slow inactivation and induce resting inactivation. AB - External H+ and Ni2+ ions inhibit Kv1.5 channels by increasing current decay during a depolarizing pulse and reducing the maximal conductance. Although the former may be attributed to an enhancement of slow inactivation occurring from the open state, the latter cannot. Instead, we propose that the loss of conductance is due to the induction, by H+ or Ni2+, of a resting inactivation process. To assess whether the two inactivation processes are mechanistically related, we examined the time courses for the onset of and recovery from H+- or Ni2+-enhanced slow inactivation and resting inactivation. Compared to the time course of H+- or Ni2+-enhanced slow inactivation at +50 mV, the onset of resting inactivation induced at 80 mV with either ion involves a relatively slower process. Recovery from slow inactivation under control conditions was bi exponential, indicative of at least two inactivated states. Recovery following H+ or Ni2+-enhanced slow inactivation or resting inactivation had time constants similar to those for recovery from control slow inactivation, although H+ and Ni2+ biased inactivation towards states from which recovery was fast and slow, respectively. The shared time constants suggest that the H+- and Ni2+-enhanced slow inactivated and induced resting inactivated states are similar to those visited during control slow inactivation at pH 7.4. We conclude that in Kv1.5 H+ and Ni2+ differentially enhance a slow inactivation process that involves at least two inactivated states and that resting inactivation is probably a close variant of slow inactivation. PMID- 20581044 TI - Discovery and rediscoveries of Golgi cells. AB - When Camillo Golgi invented the black reaction in 1873 and first described the fine anatomical structure of the nervous system, he described a 'big nerve cell' that later took his name, the Golgi cell of cerebellum ('Golgi'schen Zellen', Gustaf Retzius, 1892). The Golgi cell was then proposed as the prototype of type II interneurons, which form complex connections and exert their actions exclusively within the local network. Santiago Ramon y Cajal (who received the Nobel Prize with Golgi in 1906) proceeded to a detailed description of Golgi cell morphological characteristics, but functional insight remained very limited for many years. The first rediscovery happened in the 1960s, when neurophysiological analysis in vivo revealed that Golgi cells are inhibitory interneurons. This finding promoted the development of two major cerebellar theories, the 'beam theory' of John Eccles and the 'motor learning theory' of David Marr, in which the Golgi cells regulate the spatial organisation and the gain of input signals to be processed and learned by the cerebellar circuit. However, the matter was not set and a series of pioneering observations using single unit recordings and electronmicroscopy raised new issues that could not be fully explored until the 1990s. Then, the advent of new electrophysiological and imaging techniques in vitro and in vivo demonstrated the cellular and network activities of these neurons. Now we know that Golgi cells, through complex systems of chemical and electrical synapses, effectively control the spatio-temporal organisation of cerebellar responses. The Golgi cells regulate the timing and number of spikes emitted by granule cells and coordinate their coherent activity. Moreover, the Golgi cells regulate the induction of long-term synaptic plasticity along the mossy fibre pathway. Eventually, the Golgi cells transform the granular layer of cerebellum into an adaptable spatio-temporal filter capable of performing several kinds of logical operation. After more than a century, Golgi's intuition that the Golgi cell had to generate under a new perspective complex ensemble effects at the network level has finally been demonstrated. PMID- 20581045 TI - Caveolin-1 P132L mutation in human cancers: 1 CAVeat to be voiced. PMID- 20581046 TI - Absence of the caveolin-1 P132L mutation in cancers of the breast and other organs. AB - Caveolin-1 belongs to a family of scaffolding proteins, and the P132L point mutation of this gene has been found in up to 16% of all examined breast cancers. Subsequent studies have revealed that the P132L mutation exerts a dominant negative effect through misfolding during caveolin-1 oligomerization. However, this mutation has not been validated in other series of breast cancer samples. Contradictory to the suggested tumor suppressor function, overexpression of caveolin-1 is common in various cancer types. To clarify these inconsistent results, we examined the caveolin-1 mutation in a large series of breast cancer specimens. We first used a standard direct sequencing method and found that none of the 99 breast cancers tested had this mutation. Then we developed a sensitive method for a paraffin section that could detect the mutant allele at a rate of as little as 0.1% among wild-type allele copies. Even when using this sensitive method, none of the 80 estrogen receptor-positive breast tumors had the P132L mutation. Furthermore, 270 cancers in various organs were examined, and no caveolin-1 mutations were detected. These results raise doubt about the presence of the caveolin-1 P132L mutation in breast cancer and other cancer types, and thus further studies are warranted. PMID- 20581047 TI - Immiscible phase nucleic acid purification eliminates PCR inhibitors with a single pass of paramagnetic particles through a hydrophobic liquid. AB - Extraction and purification of nucleic acids from complex biological samples for PCR are critical steps because inhibitors must be removed that can affect reaction efficiency and the accuracy of results. This preanalytical processing generally involves capturing nucleic acids on microparticles that are then washed with a series of buffers to desorb and dilute out interfering substances. We have developed a novel purification method that replaces multiple wash steps with a single pass of paramagnetic particles (PMPs) though an immiscible hydrophobic liquid. Only two aqueous solutions are required: a lysis buffer, in which nucleic acids are captured on PMPs, and an elution buffer, in which they are released for amplification. The PMPs containing the nucleic acids are magnetically transported through a channel containing liquid wax that connects the lysis chamber to the elution chamber in a specially designed cartridge. Transporting PMPs through the immiscible phase yielded DNA and RNA as pure as that obtained after extensive wash steps required by comparable purification methods. Our immiscible-phase process has been applied to targets in whole blood, plasma, and urine and will enable the development of faster and simpler purification systems. PMID- 20581048 TI - An echocardiographic model predicting severity of aortic regurgitation in congenital heart disease. AB - Background- Multiple echocardiographic parameters have been identified to predict the severity of aortic regurgitation (AR) with variable reliability. This study was performed to identify which echocardiographic parameters best predict the severity of AR in a cohort of patients with congenital heart disease, using cardiovascular MRI quantification as a reference standard. Methods and Results- The study involved 2 phases. In phase 1, predictive models were developed on the basis of multivariable analysis of various morphometric and Doppler variables obtained from 174 echocardiograms that best predicted the severity of AR as defined by paired cardiovascular MRI examinations. A nonlinear estimate of regurgitation fraction, using the variables parasternal vena contracta-derived area divided by body surface area and abdominal aorta Doppler retrograde velocity time integral divided by antegrade velocity-time integral, was identified through multivariable analysis as the best predictive model for AR fraction. In phase 2, the predictive models were prospectively tested on 43 echocardiographic examinations for which a paired cardiovascular MRI was performed. The agreement between the observed and predicted AR fraction was assessed using Bland-Altman analysis. For the 30 studies of the validation data set that had adequate quality images of both the parasternal vena contracta width and the abdominal aorta flow profile, the predicted AR values had a mean bias+/-SD of 0.4+/-7.3% (P=0.80). Conclusions- A model using the 2 variables parasternal vena contracta-derived area divided by body surface area and abdominal aorta Doppler retrograde velocity time integral divided by antegrade velocity-time integral can predict AR severity in patients with a wide variety of congenital heart disease. PMID- 20581049 TI - Kinetics of left ventricular strains and torsion during incremental exercise in healthy subjects: the key role of torsional mechanics for systolic-diastolic coupling. AB - BACKGROUND: The dynamics of systolic and diastolic strains and torsional mechanics of the left ventricle (LV) and their relation to diastolic filling never have been evaluated at various exercise intensities. METHODS AND RESULTS: Speckle tracking echocardiography was performed in 20 healthy sedentary subjects at rest and during a progressive submaximal exercise test at 20%, 30%, and 40% of maximal aerobic power. LV twist increased progressively with exercise intensity (10.5 +/- 3.2 to 15.8 +/- 4.5 degrees ; P<0.001), whereas longitudinal strain remained unchanged after the first workload, underlining the key role of torsional reserve in systolic-diastolic coupling during exercise. The increase in diastolic untwisting (-88.7 +/- 34.2 to -182.9 +/- 53.5 deg . s(-1); P<0.01) was correlated to enhanced systolic twist (R=0.61; P<0.001), and its magnitude of increase was significantly higher compared to diastolic longitudinal and circumferential strain rates (119 +/- 64% versus 65 +/- 44% and 57 +/- 24%, respectively), emphasizing its contribution to diastolic filling. The timing of peak untwisting and the chronology of diastolic mechanical events were unchanged during effort. Untwisting was driven mainly by apical rotation and determined mitral opening and isovolumic relaxation time (R=0.47 and 0.61, respectively; P<0.001), whereas basal rotation and longitudinal and circumferential diastolic strain rates were major determinants of increased early diastolic filling (R=0.64, 0.79, and 0.81, respectively; P<0.001). CONCLUSIONS: The use of speckle tracking echocardiography gives new insights into physiological adaptive LV mechanics during incremental exercise in healthy subjects, underlining the key role of torsional mechanics. It might be useful to better understand the mechanisms of diastolic dysfunction and exercise intolerance in various pathological conditions. PMID- 20581050 TI - Reference values and distribution of conventional echocardiographic Doppler measures and longitudinal tissue Doppler velocities in a population free from cardiovascular disease. AB - BACKGROUND: This study aimed to investigate the distribution of conventional Doppler measurements, pulsed wave tissue Doppler imaging (pwTDI)- and color tissue Doppler imaging-derived velocities, by age and sex in a healthy population. METHODS AND RESULTS: Longitudinal tissue Doppler velocities were determined in 1266 healthy individuals from standard apical 4- and 2-chamber views. By the pwTDI method, mean +/- SD systolic mitral annular velocities were 8.2 +/- 1.3 cm/s in women and 8.6 +/- 1.4 cm/s in men, and by color tissue Doppler, they were 6.6 +/- 1.1 cm/s in women and 6.9 +/- 1.3 cm/s in men. With pwTDI, diastolic early mitral annular velocities were 11.8 +/- 3.2 cm/s in women and 10.8 +/- 3.0 cm/s in men, with corresponding ratios between mitral early flow velocity and early diastolic tissue velocity of 6.7 +/- 0.8 in women and 6.4 +/- 0.8 in men. By pwTDI, tricuspid annular systolic and early diastolic velocities were 12.5 +/- 1.9 and 13.3 +/- 3.0, respectively, in women and 12.8 +/- 2.2 and 12.5 +/- 3.3, respectively, in men. There was a significant decrease in left and right ventricular function with increasing age. Conclusions- The longitudinal mitral and tricuspid annular velocities from this population study are widely applicable as reference values. Reference values for annular velocities should be specified by sex and age. The average of inferoseptal and anterolateral wall velocities may be the preferred index of left ventricular performance. PMID- 20581051 TI - Novel molecular imaging approach for subclinical detection of iritis and evaluation of therapeutic success. AB - There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. Acute anterior chamber inflammation is the most common form of uveitis and a major cause of vision loss. The proximity of the iris vasculature to the light-permeable cornea and its involvement in ocular inflammation make it an ideal target for noninvasive molecular imaging. To accomplish this, carboxylated fluorescent microspheres (MSs) were conjugated with recombinant P-selectin glycoprotein ligand-1 and systemically injected in endotoxin-induced uveitic animals. MS adhesion in the microcirculation of the anterior and posterior chamber was visualized by intravital microscopy and scanning laser ophthalmoscopy. In iritic animals, significantly higher numbers of recombinant P-selectin glycoprotein ligand-1 conjugated MSs adhered to the endothelium (P = 0.03) matching the increase in leukocyte adhesion. Conjugated MSs specifically interacted with firmly adhering leukocytes, allowing quantification of the endogenous immune response. Topical eye drop treatment with dexamethasone (P < 0.01) or cyclosporine A (P < 0.01) significantly lowered MS adhesion in iris vessels. Surprisingly, topical dexamethasone significantly reduced MS interaction in the fundus vessels (P < 0.01), while cyclosporine A did not. In vivo MS accumulation preceded clinical signs of anterior uveitis and leukocyte adhesion in iris vasculature. This work introduces noninvasive subclinical detection of endothelial injury in the iris vasculature, providing a unique opportunity for quantifying vascular injury and immune response in vivo. PMID- 20581052 TI - Engraftment of cells from porcine islets of Langerhans and normalization of glucose tolerance following transplantation of pig pancreatic primordia in nonimmune-suppressed diabetic rats. AB - Transplantation therapy for human diabetes is limited by the toxicity of immunosuppressive drugs. However, even if toxicity can be minimalized, there will still be a shortage of human donor organs. Xenotransplantation of porcine islets may be a strategy to overcome these supply problems. Xenotransplantation in mesentery of pig pancreatic primordia obtained very early during organogenesis [embryonic day 28 (E28)] can obviate the need for immune suppression in rats or rhesus macaques. Here, in rats transplanted previously with E28 pig pancreatic primordia in the mesentery, we show normalization of glucose tolerance in nonimmune-suppressed streptozotocin-diabetic LEW rats and insulin and porcine proinsulin mRNA-expressing cell engraftment in the kidney following implantation of porcine islets beneath the renal capsule. Donor cell engraftment was confirmed using fluorescent in situ hybridization for the porcine X chromosome and electron microscopy. In contrast, cells from islets did not engraft in the kidney without prior transplantation of E28 pig pancreatic primordia in the mesentery. This is the first report of prolonged engraftment and sustained normalization of glucose tolerance following transplantation of porcine islets in nonimmune-suppressed, immune-competent rodents. The data are consistent with tolerance induction to a cell component of porcine islets induced by previous transplantation of E28 pig pancreatic primordia. PMID- 20581053 TI - Cytoskeletal regulation of epithelial barrier function during inflammation. AB - Increased epithelial permeability is a common and important consequence of mucosal inflammation that results in perturbed body homeostasis and enhanced exposure to external pathogens. The integrity and barrier properties of epithelial layers are regulated by specialized adhesive plasma membrane structures known as intercellular junctions. It is generally believed that inflammatory stimuli increase transepithelial permeability by inducing junctional disassembly. This review highlights molecular events that lead to disruption of epithelial junctions during inflammation. We specifically focus on key mechanisms of junctional regulation that are dependent on reorganization of the perijunctional F-actin cytoskeleton. We discuss critical roles of myosin-II dependent contractility and actin filament turnover in remodeling of the F-actin cytoskeleton that drive disruption of epithelial barriers under different inflammatory conditions. Finally, we highlight signaling pathways induced by inflammatory mediators that regulate reorganization of actin filaments and junctional disassembly in mucosal epithelia. PMID- 20581055 TI - TLR9 signaling is required for generation of the adaptive immune protection in Cryptococcus neoformans-infected lungs. AB - To determine whether TLR9 signaling contributes to the development of the adaptive immune response to cryptococcal infection, wild-type (TLR9+/+) and TLR9 knockout (TLR9-/-) BALB/c mice were infected intratracheally with 10(4) C. neoformans 52D. We evaluated 1) organ microbial burdens, 2) pulmonary leukocyte recruitment, 3) pulmonary and systemic cytokine induction, and 4) macrophage activation profiles. TLR9 deletion did not affect pulmonary growth during the innate phase, but profoundly impaired pulmonary clearance during the adaptive phase of the immune response (a 1000-fold difference at week 6). The impaired clearance in TLR9-/- mice was associated with: 1) significantly reduced CD4(+), CD8+ T cell, and CD19+ B cell recruitment into the lungs; 2) defects in Th polarization indicated by altered cytokine responses in the lungs, lymphonodes, and spleen; and 3) diminished macrophage accumulation and altered activation profile, including robust up-regulation of Arg1 and FIZZ1 (indicators of alternative activation) and diminished induction of inducible nitric oxide synthase (an indicator of classical activation). Histological analysis revealed defects in granuloma formation and increased numbers of intracellular yeast residing within macrophages in the lungs of TLR9-/- mice. We conclude that TLR9 signaling plays an important role in the development of robust protective immunity, proper recruitment and function of effector cells (lymphocytes and macrophages), and, ultimately, effective cryptococcal clearance from the infected lungs. PMID- 20581056 TI - HIV-associated nephropathy: role of mammalian target of rapamycin pathway. AB - Both glomerular and tubular lesions are characterized by a proliferative phenotype in HIV-associated nephropathy. We hypothesized that mammalian target of rapamycin (mTOR) contributes to the development of the HIVAN phenotype. Both glomerular and tubular epithelial cells showed enhanced expression of phospho (p) mTOR in HIV-1 transgenic mice (Tgs). In addition, renal tissues of transgenic mice (RT-Tg) showed enhanced phosphorylation of p70S6 kinase and an associated diminished phosphorylation of eEF2. Moreover, RT-Tgs showed enhanced phosphorylation of 4EBP1 and eIF4B; these findings indicated activation of the mTOR pathway in RT-Tgs. To test our hypothesis, age- and sex-matched control mice and Tgs were administered either saline or rapamycin (an inhibitor of the mTOR pathway) for 4 weeks. Tgs receiving rapamycin not only showed inhibition of the mTOR-associated downstream signaling but also displayed attenuated renal lesions. RT-Tgs showed enhanced expression of hypoxia-inducible factor-alpha and also displayed increased expression of vascular endothelial growth factor; on the other hand, rapamycin inhibited RT-Tg expression of both hypoxia-inducible factor alpha and vascular endothelial growth factor. We conclude that the mTOR pathway contributes to the HIVAN phenotype and that inhibition of the mTOR pathway can be used as a therapeutic strategy to alter the course of HIVAN. PMID- 20581057 TI - S100A6 overexpression is associated with poor prognosis and is epigenetically up regulated in gastric cancer. AB - S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation. PMID- 20581058 TI - Loss of estrogen receptor 1 enhances cervical cancer invasion. AB - If left untreated, some cervical high-grade squamous intraepithelial lesions will progress to invasive squamous cell carcinoma (SCC), but the molecular events conferring invasive potential remain poorly defined. In prior work, we identified 48 genes that were down-regulated in SCCs compared with high-grade squamous intraepithelial lesions and normal squamous epithelia. In this study, a functional screening strategy was used to identify which of these genes regulate cervical cancer cell invasion. Two independent squamous epithelial cell lines were transduced with a library of short hairpin RNAs targeting the differentially expressed genes and tested for invasion of the chick chorioallantoic membrane. PCR was used to recover specific short hairpin RNAs from cells that invaded the chorioallantoic membrane. Constructs targeting estrogen receptor 1 (ESR1) were highly enriched in the invasive cells. The short hairpin RNA-mediated inhibition of ESR1 in SCC- and precancer-derived cell lines increased invasiveness in both in vivo and in vitro assays. Conversely, restoration of ESR1 expression in ESR1 negative cervical cancer cells reduced cell invasiveness. Loss of ESR1 expression was found to accompany cervical cancer progression in an analysis of primary normal cervix, low grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and SCC specimens. Molecular mechanisms underlying down regulation of ESR1 in invasive cervical carcinomas appear to be complex and likely heterogeneous. Our findings indicate that loss of ESR1 has a major role in mediating cervical cancer invasion and progression. PMID- 20581059 TI - Endothelial caveolae and caveolin-1 as key regulators of atherosclerosis. AB - This commentary discusses the role of caveolin-1 in atherosclerosis. PMID- 20581060 TI - Polo-like kinase 1 as predictive marker and therapeutic target for radiotherapy in rectal cancer. AB - The ability to predict tumor sensitivity toward radiotherapy may significantly impact the selection of patients for preoperative combined-modality therapy. The aim of the present study was to test the predictive value of Polo-like kinase 1 (PLK1) in rectal cancer patients and to investigate whether PLK1 plays a direct role in mediating radiation sensitivity. PLK1 expression was evaluated by immunohistochemistry (n = 76) or Affymetrix HG133 microarray (n = 20) on pretreatment biopsies of patients with advanced rectal cancer. Expression was correlated with both tumor regression in the resected specimen and long-term clinical outcome. Furthermore, we used small interfering RNAs (siRNAs) to down regulate PLK1 expression in colorectal cancer cells and analyzed the effects of PLK1-specific siRNAs by Western blot and quantitative real-time PCR analysis, FACScan analysis, caspase 3/7 assays, and colony-forming assays. We observed that increased PLK1 protein expression was significantly related to a poorer tumor regression and a higher risk of local recurrence in uni- and multivariate analysis. A significant decrease of PLK1 expression by siRNAs in combination with ionizing radiation induced an increased percentage of apoptotic cells and increased caspase 3/7 activity. Furthermore, enhanced G(2)-M levels, decreased cellular viability, and reduced clonogenic survival were demonstrated, indicating a radiosensitizing effect of PLK1 depletion. Therefore, PLK1 may be a novel predictive marker for radiation response as well as a promising therapeutic target in rectal cancer patients. PMID- 20581061 TI - Endothelial-specific overexpression of caveolin-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. AB - Caveolin-1 (Cav-1) is the major structural protein essential to the formation of the caveolae in endothelial cells. Genetic ablation of Cav-1 on an apolipoprotein E knockout background inhibits the progression of atherosclerosis, whereas re expression of Cav-1 in the endothelium promotes lesion expansion. Although Cav-1 null mice are useful to delineate the importance of caveolae in atherosclerosis, there are additional problems that are difficult to dissect because loss of Cav-1 abolishes both the caveolae organelle as well as the Cav-1-mediated signaling pathways. To study how Cav-1 influences the progression of atherosclerosis in mice with caveolae, we generated a transgenic mouse that overexpresses Cav-1 in the endothelial cells in an apolipoprotein E-deficient background. We found that endothelial-specific overexpression of Cav-1 enhanced the progression of atherosclerosis in mice. Mechanistically, overexpression of Cav-1 reduced endothelial cell proliferation, migration, and nitric oxide production in vitro and increased expression of vascular cell adhesion molecule-1 in vivo. PMID- 20581063 TI - Differentiation among glioblastoma multiforme, solitary metastatic tumor, and lymphoma using whole-tumor histogram analysis of the normalized cerebral blood volume in enhancing and perienhancing lesions. AB - BACKGROUND AND PURPOSE: The histogram method has been shown to demonstrate heterogeneous morphologic features of tumor vascularity. This study aimed to determine whether whole-tumor histogram analysis of the normalized CBV for contrast-enhancing lesions and perienhancing lesions can differentiate among GBMs, SMTs, and lymphomas. MATERIALS AND METHODS: Fifty-nine patients with histopathologically confirmed GBMs (n = 28), SMTs (n = 22), or lymphomas (n = 12) underwent conventional MR imaging and dynamic susceptibility contrast-enhanced imaging before surgery. Histogram distribution of the normalized CBV was obtained from whole-tumor voxels in contrast-enhancing lesions and perienhancing lesions. The HW, PHP, and MV were determined from histograms. One-way ANOVA was used initially to test the overall equality of mean values for each type of tumor. Subsequently, posttest multiple comparisons were performed. RESULTS: For whole tumor histogram analyses for contrast-enhancing lesions, only PHP could differentiate among GBMs (4.79 +/- 1.31), SMTs (3.32 +/- 1.10), and lymphomas (2.08 +/- 0.54). The parameters HW and MV were not significantly different between GBMs and SMTs, whereas the 2 histogram parameters were significantly higher in GBMs and SMTs compared with lymphomas. For the analyses of perienhancing lesions, only MV could differentiate among GBMs (1.90 +/- 0.26), SMTs (0.80 +/- 0.21), and lymphomas (1.27 +/- 0.34). HW and PHP were not significantly different between SMTs and lymphomas. CONCLUSIONS: Using a whole tumor histogram analysis of normalized CBV for contrast-enhancing lesions and perienhancing lesions facilitates differentiation of GBMs, SMTs and lymphomas. PMID- 20581062 TI - Abnormal presence of the matrix extracellular phosphoglycoprotein-derived acidic serine- and aspartate-rich motif peptide in human hypophosphatemic dentin. AB - Severe dental troubles are associated with X-linked hypophosphatemic rickets and are mainly related to impaired dentin mineralization. In dentin matrix, matrix extracellular phosphoglycoprotein (MEPE) may be protected from proteolysis by a specific interaction with PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome). The objective of our work was to determine whether PHEX impairment induces MEPE cleavage in dentin and the subsequent release of the C-terminal acidic serine- and aspartate-rich motif (ASARM) peptide, which is known to inhibit mineralization. By Western blot analysis, we explored dentin extracts from seven hypophosphatemic patients with mutations of the PHEX gene. A proteomic approach combining immunoprecipitation, surface enhanced laser desorption/ionization-time of flight-mass spectrometry and matrix assisted laser desorption ionization-time of flight analysis of the samples completed this exploration. This study shows a 4.1-kDa peptide containing the MEPE-derived ASARM peptide in hypophosphatemic samples. The presence of ASARM was less marked in patients treated with 1-hydroxylated vitamin D and phosphate during growth. Moreover, recombinant ASARM implanted in a rat pulp injury model disturbed the formation of the reparative dentin bridge. These results suggest that abnormal MEPE cleavage occurs when PHEX activity is deficient in humans, the ASARM peptide may be involved in the mineralization defects and the PHEX-MEPE interaction may be indirect, as ensuring a better phosphate and vitamin D environment to the mineralizing dentin prevents MEPE cleavage. PMID- 20581064 TI - "Giant" arachnoid granulations just like CSF?: NOT!! AB - "Giant" AGs (>1 cm) are uncommon and can be misdiagnosed as venous sinus pathology such as a neoplasm or thrombosis. Seventeen patients with a total of 19 venous sinus AGs of >1 cm were collected from contributing authors. MR imaging was available for all AGs; CT, for 5/19; and DSA, for 7/19. Intra-AG fluid was compared with CSF in subarachnoid spaces. Nonfluid AG tissue was compared with gray matter. Diagnosis was based on imaging findings. Fluid within giant AGs did not follow CSF signal intensity on at least 1 MR image in nearly 80% (15/19) of AGs. Nine of these 15 AGs had CSF-incongruent signal intensity on >=2 MR images. CSF-incongruent signal intensity was seen in 8/8 AGs on FLAIR, 7/10 on precontrast T1WI, 13/19 on T2WI, and 8/14 on contrast-enhanced T1WI. Nonfluid signal intensity was present in 18/19 AGs and varied from absent/hypointense (intra-AG flow voids) to gray matter isointense (stromal tissue). PMID- 20581065 TI - Sonographic differentiation of asymptomatic diffuse thyroid disease from normal thyroid: a prospective study. AB - BACKGROUND AND PURPOSE: There is no useful guide or study related to the differentiation of asymptomatic diffuse thyroid disease from normal thyroid by using thyroid US. This study was prospectively designed to evaluate the efficacy of the use of real-time thyroid sonography as performed by an experienced radiologist for the identification of asymptomatic DTD. MATERIALS AND METHODS: From January 2008 to December 2008, 2267 patients underwent thyroid sonography in our hospital by 1 radiologist. Each patient's thyroid was prospectively classified as being in 1 of 4 of the following diagnostic categories on the basis of the sonographic features as determined with the use of real-time sonography: suggestive for DTD, suspicious for DTD, indeterminate, and no evidence of DTD. We calculated the diagnostic efficacy of the sonographic classifications compared with the pathology results. RESULTS: Sonographic classifications for DTD in 340 patients who underwent thyroid surgery because of thyroid malignancy or other causes included the following: suggestive for DTD (n = 32), suspicious for DTD (n = 39), indeterminate (n = 18), and no evidence of DTD (n = 251). On the pathology, HT (n = 33), chronic lymphocytic thyroiditis (n = 27), diffuse hyperplasia (n = 2), and NTP (n = 278) were identified. There were true-positive cases (n = 50), true-negative cases (n = 244), false-positive cases (n = 21), and false-negative cases (n = 7). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for a diagnosis of asymptomatic DTD were 87.7%, 92.1%, 70.4%, 97.2%and 91.3%, respectively. CONCLUSIONS: The present sonographic classification based on real-time sonography of the thyroid is a useful tool for differentiating asymptomatic DTD from normal thyroid. PMID- 20581066 TI - Perfusion CT in acute ischemic stroke: a qualitative and quantitative comparison of deconvolution and maximum slope approach. AB - BACKGROUND AND PURPOSE: PCT postprocessing commonly uses either the MS or a variant of the DC approach for modeling of voxel-based time-attenuation curves. There is an ongoing discussion about the respective merits and limitations of both methods, frequently on the basis of theoretic reasoning or simulated data. We performed a qualitative and quantitative comparison of DC and MS by using identical source datasets and preprocessing parameters. MATERIALS AND METHODS: From the PCT data of 50 patients with acute ischemic stroke, color maps of CBF, CBV, and various temporal parameters were calculated with software implementing both DC and MS algorithms. Color maps were qualitatively categorized. Quantitative region-of-interest-based measurements were made in nonischemic GM and WM, suspected penumbra, and suspected infarction core. Qualitative results, quantitative results, and PCT lesion sizes from DC and MS were statistically compared. RESULTS: CBF and CBV color maps based on DC and MS were of comparably high quality. Quantitative CBF and CBV values calculated by DC and MS were within the same range in nonischemic regions. In suspected penumbra regions, average CBF(DC) was lower than CBF(MS). In suspected infarction core regions, average CBV(DC) was similar to CBV(MS). Using adapted tissue-at-risk/nonviable-tissue thresholds, we found excellent correlation of DC and MS lesion sizes. CONCLUSIONS: DC and MS yielded comparable qualitative and quantitative results. Lesion sizes indicated by DC and MS showed excellent agreement when using adapted thresholds. In all cases, the same therapy decision would have been made. PMID- 20581067 TI - Application of a semiautomated contour segmentation tool to identify the intervertebral nucleus pulposus in MR images. AB - BACKGROUND AND PURPOSE: Accurate identification of the NP in MR images is crucial to properly and objectively assess the intervertebral disk. Therefore, computerized segmentation of the NP in T2WI is necessary to produce repeatable and accurate results with minimal user input. MATERIAL AND METHODS: A semiautomated CS method was developed to identify the NP in T2WI on the basis of intensity differences compared with the AF. The method was validated by segmenting computer-generated images with a known ROI. The method was tested by using 63 MR images of rabbit lumbar disks, which were segmented to detect disk degeneration. An ICC was used to assess the repeatability of this method compared with manual segmentation. RESULTS: The error in the detected area of the rabbit NP by using CS was -3.49% +/- 4.4% (mean +/- SD) compared with 22.36% +/- 5.55% by using manual segmentation. Moreover, the method was capable of detecting disk degeneration in a known rabbit puncture model of disk degeneration. Finally, this method had an ICC of 0.97 and 0.99 in regard to segmenting the area and calculating the MR imaging index of the NP, deeming it highly repeatable. CONCLUSIONS: The CS method is a semiautomated computer method able to segment the NP of the rabbit disk and detect disk degeneration. In addition, it could assist in clinical detection, assessment, and monitoring of early degeneration in human disks. PMID- 20581069 TI - Cavitating leukoencephalopathy in a child carrying the mitochondrial A8344G mutation. PMID- 20581068 TI - Practical scoring system for the identification of patients with intracerebral hemorrhage at highest risk of harboring an underlying vascular etiology: the Secondary Intracerebral Hemorrhage Score. AB - BACKGROUND AND PURPOSE: An ICH patient's risk of harboring an underlying vascular etiology varies according to baseline clinical and NCCT characteristics. Our aim was to develop a practical scoring system to stratify patients with ICH according to their risk of harboring a vascular etiology. MATERIALS AND METHODS: Using a data base of 623 patients with ICH evaluated with MDCTA during a 9-year period, we developed a scoring system based on baseline clinical characteristics (age group [0-2 points], sex [0-1 point], neither known HTN nor impaired coagulation [0-1 point]), and NCCT categorization (0-2 points) to predict the risk of harboring a vascular lesion as the ICH etiology (SICH score). We subsequently applied the SICH score to a prospective cohort of 222 patients with ICH who presented to our emergency department during a 13-month period. Using ROC analysis, we calculated the AUC and MOP for the SICH score in both the retrospective and prospective patient cohorts separately and the entire patient population. Patients with SAH in the basal cisterns were excluded. RESULTS: A vascular etiology was found in 120 of 845 patients with ICH evaluated with MDCTA (14.2%), most commonly AVMs (45.8%), aneurysms with purely intraparenchymal rupture (21.7%), and DVSTs (16.7%). The MOP was reached at a SICH score of >2, with the highest incidence of vascular ICH etiologies in patients with SICH scores of 3 (18.5%), 4 (39%), 5 (84.2%), and 6 (100%). There was no significant difference in the AUC between both patient cohorts (0.86-0.87). CONCLUSIONS: The SICH score successfully predicts a given ICH patient's risk of harboring an underlying vascular etiology and could be used as a guide to select patients with ICH for neurovascular evaluation to exclude the presence of a vascular abnormality. PMID- 20581070 TI - The Holy Grail and the quest for the gold standard. PMID- 20581071 TI - Further in-depth look at superficial siderosis (and intracranial hypotension). PMID- 20581072 TI - Proton MR spectroscopy of brain abscesses. PMID- 20581073 TI - Reconciling neuroimaging and clinical findings in Aicardi-Goutieres syndrome: an autoimmune-mediated encephalopathy. PMID- 20581074 TI - Grief interrupted: the experience of loss among incarcerated women. AB - Incarcerated women face a number of stressors apart from the actual incarceration. Nearly half of all women in prison experience the death of a loved one during their incarceration. Our purpose for this study was to explore the experience of grief and loss among incarcerated women using a phenomenological method. Our study approach followed van Manen's method of phenomenology and Munhall's description of existential lifeworlds. Our analysis revealed four existential lifeworlds: temporality: frozen in time; spatiality: no place, no space to grieve; corporeality: buried emotions; and relationality: never alone, yet feeling so lonely. The findings generated from this study can help mental health providers as well as correctional professionals develop policies and programs that facilitate the grief process of incarcerated women within the confines of imprisonment. PMID- 20581075 TI - Unpacking assumptions about inclusion in community-based health promotion: perspectives of women living in poverty. AB - Community-based health promoters often aim to facilitate "inclusion" when working with marginalized women to address their exclusion and related health issues. Yet the notion of inclusion has not been critically interrogated within this field, resulting in the perpetuation of assumptions that oversimplify it. We provide qualitative evidence on inclusion as a health-promotion strategy from the perspectives of women living in poverty. We collected data with women engaged in a 6-year community-based health promotion and feminist participatory action research project. Participants' experiences illustrated that inclusion was a multidimensional process that involved a dynamic interplay between structural determinants and individual agency. The women named multiple elements of inclusion across psychosocial, relational, organizational, and participatory dimensions. This knowledge interrupts assumptions that inclusion is achievable and desirable for so-called recipients of such initiatives. We thus call for critical consideration of the complexities, limitations, and possibilities of facilitating inclusion as a health-promotion strategy. PMID- 20581076 TI - Outside looking in: the lived experience of adults with prematurely born siblings. AB - Siblings have unique relationships; however, not all sibling relationships are typical. In North America, the preterm birth rate ranks second only to Africa in a global climate of rising preterm birth rates. A paucity of literature exists for sibling relationships when one sibling is born prematurely. In this hermeneutic phenomenological study, we explored the lived experience of adult siblings with prematurely born, young adult brothers and sisters who subsequently developed disabilities. The 28 siblings, interviewed with open-ended questions, represented 47 families with extremely-low-birth-weight young adults with neurodevelopmental disabilities born between 1977 and 1982. Existential reflection guided by van Manen's human science approach assisted the analysis of tape-recorded conversations. A structure of meaning entitled "outside looking in" emerged to illustrate the extraordinary relationships forged by the adult siblings with their brothers and sisters throughout their years together. PMID- 20581077 TI - Composite primary neuronal high-content screening assay for Huntington's disease incorporating non-cell-autonomous interactions. AB - Huntington's disease (HD) is a fatal neurodegenerative disease characterized by progressive cognitive, behavioral, and motor deficits and caused by expansion of a polyglutamine repeat in the Huntingtin protein (Htt). Despite its monogenic nature, HD pathogenesis includes obligatory non-cell-autonomous pathways involving both the cortex and the striatum, and therefore effective recapitulation of relevant HD disease pathways in cell lines and primary neuronal monocultures is intrinsically limited. To address this, the authors developed an automated high-content imaging screen in high-density primary cultures of cortical and striatal neurons together with supporting glial cells. Cortical and striatal neurons are transfected separately with different fluorescent protein markers such that image-based high-content analysis can be used to assay these neuronal populations separately but still supporting their intercellular interactions, including abundant synaptic interconnectivity. This assay was reduced to practice using transfection of a mutant N-terminal Htt domain and validated via a screen of ~400 selected small molecules. Both expected as well as novel candidate targets for HD emerged from this screen; of particular interest were target classes with close relative proximity to clinical testing. These findings suggest that composite primary cultures incorporating increased levels of biological complexity can be used for high-content imaging and "high-context" screening to represent molecular targets that otherwise may be operant only in the complex tissue environment found in vivo during disease pathogenesis. PMID- 20581078 TI - Development of a fluorescent intensity assay amenable for high-throughput screening for determining 15-lipoxygenase activity. AB - 15-Lipoxygenase-1 catalyzes the introduction of molecular oxygen into polyunsaturated fatty acids to form a lipid hydroperoxide. The authors have developed an assay for the detection of lipid hydroperoxides formed by human 15 lipoxygenase (15-LO) in enzyme or cellular assays using either a 96-well or a 384 well format. The assays described take advantage of the ability of lipid hydroperoxides to oxidize nonfluorescent diphenyl-1-pyrenylphosphine (DPPP) to a fluorescent phosphine oxide. Oxidation of DPPP yields a fluorescent compound, which is not sensitive to temperature and is stable for more than 2 h. The assay is sensitive toward inhibition and robust with a Z' value of 0.79 and 0.4 in a 96 and 384-well format, respectively, and thus amenable for high-throughput screening. The utility of DPPP as a marker for 15-lipoxygenase activity was demonstrated with both enzyme- and cell-based assays for the identification of hits and to determine potency by IC(50) determinations. PMID- 20581079 TI - Exercise and the onset of disability in later life. AB - OBJECTIVE: This study was to examine whether overall physical activity levels, and different types of earlier sporting activities, are associated with the onset of locomotor disability in early older age. METHOD: A longitudinal analysis of a general population cohort of British men and women born in the early 1930s was conducted. RESULTS: Measures of overall activity levels at age 58 did not show a relationship with locomotor disability 5-6 years later. Swimming was the only sporting activity to show any strong evidence of a protective association with later locomotor disability. DISCUSSION: The promotion of swimming in adulthood could play a role in the prevention of locomotor disability and aid people's ability to follow active living health promotion guidelines in late mid-life and early old-age. PMID- 20581080 TI - Overestimation of serum kappa free light chain concentration by immunonephelometry. PMID- 20581081 TI - Comparison of 2 human chorionic gonadotropin assays as tumor markers assays. PMID- 20581082 TI - Making DNA melting useful. PMID- 20581083 TI - Detection of androgen receptor mutations in circulating tumor cells in castration resistant prostate cancer. AB - BACKGROUND: Coding mutations in the AR (androgen receptor) gene have been identified in tissue samples from patients with advanced prostate cancer and represent a possible mechanism underlying the development of castration-resistant prostate cancer (CRPC). There is a paucity of tumor-derived tissue available for molecular studies of CRPC patients. Circulating tumor cells (CTCs) in the blood of CRPC patients represent a possible avenue for interrogating the disease of such patients. METHODS: Circulating tumor cells were captured with the CellSearch Circulating Tumor Cell (CTC) Kit and with the CellSearch Profile Kit plus Qiagen's AllPrep DNA/RNA Micro Kit for the measurement of the CTC count per 7.5 mL of blood and for the isolation of nucleic acids, respectively. The AR gene was amplified by the PCR, and mutation status and relative abundance were analyzed by applying Transgenomic's WAVE denaturing HPLC technology followed by direct sequencing. RESULTS: AR mutations were detected in 20 of 35 CRPC patients; 19 missense mutations, 2 silent mutations, 5 deletions, and 1 insertion were observed. The relative abundance of the mutants in the amplified products ranged from 5% to 50%. Many of the AR mutations were identified in surgical biopsies or at autopsy and were associated with resistance to androgen-directed therapies. CONCLUSIONS: AR mutations can be identified in CTC-enriched peripheral blood samples from CRPC patients. This approach has the potential to open new perspectives in understanding CTCs and the mechanisms for tumor progression and metastasis in CRPC. PMID- 20581085 TI - Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise. AB - This study compared the hemorheological responses of a group of sickle cell trait (SCT) carriers with those of a control (Cont) group in response to 40 min of submaximal exercise (exercise intensity, 55% aerobic peak power) performed in two conditions: one with water offered ad libitum, i.e., the hydration (Hyd) condition, and one without water, i.e., the dehydration (Dehyd) condition. Blood and plasma viscosities, as well as red blood cell rigidity, were determined at rest, at the end of exercise, and at 2 h recovery with a cone plate viscometer at high shear rate and 37 degrees C. The SCT and Cont groups lost 1 +/- 0.7 and 1.6 +/- 0.6 kg of body weight, respectively, in the Dehyd condition, indicating a significant effect of water deprivation compared with the Hyd condition, in which body weight remained unchanged. Plasma viscosity increased with exercise and returned to baseline during recovery independently of the group and condition. As previously demonstrated, resting blood viscosity was greater in the SCT carriers than in the Cont group. Blood viscosity increased by the end of exercise and returned to baseline at 2 h recovery in the Cont group in both conditions. The blood viscosity of SCT carriers did not change in response to exercise in the Dehyd condition and remained elevated at 2 h recovery. This extended hyperviscosity, in association with other biological changes induced by exercise, could be considered as a risk factor for exercise-related events in SCT carriers, similar to vasoocclusive crises, notably during the recovery. In contrast, the Hyd condition normalized the hyperviscosity and red blood cell rigidity of the SCT carriers, with blood viscosity values reaching the same lower values as those found in the Cont group during the recovery. Adequate hydration of SCT carriers should be strongly promoted to reduce the clinical risk associated with potential hyperviscosity complications. PMID- 20581084 TI - Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. AB - Self-renewing embryonic stem (ES) cells have an exceptional need for timely biomass production, yet the transcriptional control mechanisms responsible for meeting this requirement are largely unknown. We report here that Ronin (Thap11), which is essential for the self-renewal of ES cells, binds with its transcriptional coregulator, Hcf-1, to a highly conserved enhancer element that previously lacked a recognized binding factor. The subset of genes bound by Ronin/Hcf-1 function primarily in transcription initiation, mRNA splicing, and cell metabolism; genes involved in cell signaling and cell development are conspicuously underrepresented in this target gene repertoire. Although Ronin/Hcf 1 represses the expression of some target genes, its activity at promoter sites more often leads to the up-regulation of genes essential to protein biosynthesis and energy production. We propose that Ronin/Hcf-1 controls a genetic program that contributes to the unimpeded growth of ES cells. PMID- 20581087 TI - Magnesium deficiency upregulates serine palmitoyl transferase (SPT 1 and SPT 2) in cardiovascular tissues: relationship to serum ionized Mg and cytochrome c. AB - The present work tested the hypothesis that a short-term dietary deficiency of magnesium (Mg) (21 days) in rats would result in the upregulation of the two major subunits of serine palmitoyl-CoA-transferase, serine palmitoyl transferase (SPT 1) and SPT 2 (the rate-limiting enzymes responsible for the de novo biosynthesis of ceramides) in left ventricular, right ventricular, and atrial heart muscle and abdominal aortic smooth muscle, as well as induce a reduction in serum sphingomyelin concomitant with the release of mitochondrial cytochrome c (Cyto c) in these tissues. Our data indicate that short-term Mg deficiency (MgD) resulted in an upregulation of SPT 1 and SPT 2, concomitant with a very significant release of Cyto c in left ventricular, right ventricular, atrial, and abdominal aortic smooth muscle. Short-term MgD also produced a lowering of serum sphingomyelin and ionized Mg. The greater the reduction in serum ionized Mg, the greater the upregulation of SPT 1 and 2 and the more the increase in free Cyto c. The data suggest that MgD, most likely, causes a biosynthesis of ceramides via two pathways in cardiovascular tissues, viz., via the activation of serine palmitoyl-CoA-transferase and sphingomyelinase, which lead to apoptotic events via intrinsic (present study) and extrinsic pathways (previous studies). Low levels of drinking water Mg were cardio- and vasculoprotective. PMID- 20581086 TI - Hypoxic relaxation of penile arteries: involvement of endothelial nitric oxide and modulation by reactive oxygen species. AB - Although obesity-related cardiovascular disease and hypoxia are associated with erectile dysfunction, little is known about the direct effects of hypoxia on penile arteries. In the present study, the effects of acute hypoxia (Po(2) = approximately 10 Torr, 20 min) were investigated in isolated penile arteries to determine the influence of endothelium removal, nitric oxide (NO) synthase (NOS), cyclooxygenase (COX), NADPH oxidase, changes in reactive oxygen species (ROS), and a high-fat diet. Hypoxia-relaxed penile arteries contracted with phenylephrine by approximately 50%. Relaxation to hypoxia and acetylcholine was reduced by endothelium removal and by inhibition of NOS (N(omega)-nitro-l arginine) and COX (indomethacin) but was enhanced by Tempol and by NADPH oxidase inhibition with apocynin and gp91ds-tat. Basal superoxide levels detected by lucigenin chemiluminescence were reduced by Tempol and gp91ds-tat and were enhanced by NOS blockade. Hypoxic relaxant responses were enhanced by catalase and ebselen. Exogenous peroxide evoked relaxations of penile arteries, which were partially inhibited by endothelium removal and by the inhibition of COX and extracellular signal-regulated mitogen-activated protein kinase (MAPK) but enhanced by p38 MAPK blockade. The NO-dependent component of relaxation to hypoxia was impaired in penile arteries from high-fat diet-fed, obese rats associated with increased superoxide production. Thus hypoxic relaxation of penile arteries is partially mediated by endothelial NO in a manner that is normally attenuated by endogenous ROS production. Obesity further increases superoxide production and impairs the influence of NO. Therefore, cardiovascular disease involving decreased NO bioavailability and/or enhanced ROS generation may contribute to erectile dysfunction through impairing the relaxation of penile arteries to hypoxia. PMID- 20581088 TI - Molecular mechanisms mediating preconditioning following chronic ischemia differ from those in classical second window. AB - A major difference between experimental ischemic preconditioning (IPC), induced by brief ischemic episodes, and the clinical situation is that patients generally have repetitive episodes of ischemia. We used a swine model to examine differences in genes regulated by classical second-window IPC (SWOP) [two 10-min episodes of coronary artery occlusion (CAO) followed by 24 h reperfusion] compared with repetitive CAO/reperfusion (RCO), i.e., two 10-min CAO 12 h apart, and to repetitive coronary stenosis (RCS), six episodes of 90 min coronary stenosis 12 h apart (n = 5/group). All three models reduced infarct size by 60 85%, which was mediated by nitric oxide in SWOP but not in the other two models. We employed microarray analyses to discover additional molecular pathways intrinsic to models of repetitive ischemia and different from classical SWOP. There was an 85% homology in gene response between the RCO and RCS models, whereas SWOP was qualitatively different. Both RCO and RCS, but not SWOP, showed downregulation of genes encoding proteins involved in oxidative metabolism and upregulation of genes involved in protein synthesis, unfolded protein response, autophagy, heat shock response, protein secretion, and an activation of the NF kappaB signaling pathway. Therefore, the regulated genes mediating IPC with repetitive ischemia differ radically from SWOP both quantitatively and qualitatively, showing that a repetitive pattern of ischemia, rather than the difference between no-flow vs. low-flow ischemia, dictates the genomic response of the heart. These findings illustrate new cardioprotective mechanisms developed by repetitive IPC, which are potentially more relevant to patients with chronic ischemic heart disease, who are subjected to repetitive episodes of ischemia. PMID- 20581089 TI - Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. AB - Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17-24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr (n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 +/- 1.3 vs. 74 +/- 1.7 mmHg, P < 0.01), MSNA [9.94 +/- 2.0 to 14.63 +/- 1.5 bursts/min (P < 0.05); 16.89 +/- 3.2 to 26.97 +/- 3.3 bursts/100 heartbeats (hb) (P = 0.01)], and forearm vascular resistance (FVR) (35.3 +/- 5.8 vs. 55.3 +/- 6.5 mmHg x ml(-1) x min x 100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR. PMID- 20581090 TI - Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction. AB - We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K(+) current [I(Ks); long QT syndrome type 1 (LQT1)] or rapidly activating delayed rectifier K(+) current [I(Kr); long QT syndrome type 2 (LQT2)]. Rabbits with either genotype have prolonged action potential duration and QT intervals; however, only LQT2 rabbits develop atrioventricular (AV) blocks and polymorphic ventricular tachycardia. We therefore sought to characterize the genotype specific differences in AV conduction and ventricular refractoriness in LQT1 and LQT2 rabbits. We carried out in vivo electrophysiological studies in LQT1, LQT2, and littermate control (LMC) rabbits at baseline, during isoproterenol infusion, and after a bolus of dofetilide and ex vivo optical mapping studies of the AV node/His-region at baseline and during dofetilide perfusion. Under isoflurane anesthesia, LQT2 rabbits developed infra-His blocks, decremental His conduction, and prolongation of the Wenckebach cycle length. In LQT1 rabbits, dofetilide altered the His morphology and slowed His conduction, resulting in intra-His block, and additionally prolonged the ventricular refractoriness, leading to pseudo-AV block. The ventricular effective refractory period (VERP) in right ventricular apex and base was significantly longer in LQT2 than LQT1 (P < 0.05) or LMC (P < 0.01), with a greater VERP dispersion in LQT2 than LQT1 rabbits. Isoproterenol reduced the VERP dispersion in LQT2 rabbits by shortening the VERP in the base more than in the apex but had no effect on VERP in LQT1. EPS and optical mapping experiments demonstrated genotype-specific differences in AV conduction and ventricular refractoriness. The occurrence of infra-His blocks in LQT2 rabbits under isoflurane and intra-His block in LQT1 rabbits after dofetilide suggest differential regional sensitivities of the rabbit His-Purkinje system to drugs blocking I(Kr) and I(Ks). PMID- 20581091 TI - Nitric oxide-mediated negative regulation of cyclooxygenase-2 induction in vascular inflammation. PMID- 20581092 TI - The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice. AB - We hypothesized that the reciprocal association between adiponectin and lectin like oxidized LDL (ox-LDL) receptor (LOX)-1 contributes to the regulation of aortic endothelial dysfunction in atherosclerosis. To test this hypothesis, endothelium-dependent (ACh) and endothelium-independent (sodium nitroprusside) vasorelaxation of isolated aortic rings from control mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE KO mice treated with either adiponectin (15 microg x day(-1) x mouse(-1) sc for 8 days) or neutralizing antibody to LOX-1 (anti-LOX-1, 16 microg/ml, 0.1 ml/mouse ip for 7 days) were examined. Although vasorelaxation to sodium nitroprusside was not different between control and ApoE KO mice, relaxation to ACh was impaired in ApoE KO mice. Adiponectin and anti-LOX 1 restored nitric oxide-mediated endothelium-dependent vasorelaxation in ApoE KO mice. Aortic ROS formation and ox-LDL uptake were increased in ApoE KO mice. Both adiponectin and anti-LOX-1 treatment reduced ROS production and aortic ox-LDL uptake. In mouse coronary artery endothelial cells, TNF-alpha incubation increased endothelial LOX-1 expression. Adiponectin reduced TNF-alpha-induced LOX 1 expression. Consistently, in ApoE KO mice, adiponectin treatment reversed elevated LOX-1 expression in aortas. Immunofluorescence staining showed that adiponectin was mainly colocalized with endothelial cells. Although adiponectin expression was lower in ApoE KO versus control mice, anti-LOX-1 increased aortic adiponectin expression, suggesting a reciprocal regulation between adiponectin and LOX-1. Moreover, both adiponectin and anti-LOX-1 reduced NF-kappaB expression in ApoE KO mice. Thus, adiponectin and LOX-1 may converge on NF-kappaB signaling to regulate their function. In conclusion, our results indicate that the reciprocal regulation between adiponectin and LOX-1 amplifies oxidative stress and ox-LDL uptake, leading to endothelial dysfunction in atherosclerosis. PMID- 20581093 TI - Effects of dose, administration route, and/or vehicle on decabromodiphenyl ether concentrations in plasma of maternal, fetal, and neonatal rats and in milk of maternal rats. AB - The effects of route and vehicle on blood and milk levels of decabromodiphenyl ether (DecaBDE; CASRN 1163-19-5) were investigated in the rat to assist in the design and conduct of a developmental neurotoxicity study. Blood plasma and/or milk concentrations were determined in dams, fetuses, and/or nursing pups after repeated DecaBDE administration by gavage throughout gestation or gestation and lactation using corn oil (CO) or soyaphospholipon/Lutrol F 127-water (SPL) as the vehicle. The impact of vehicle on plasma levels was also investigated in pups derived from naive dams after a single postnatal dose. This study reports for the first time fetal and neonatal plasma concentrations concurrent with those of maternal plasma and/or milk. Higher concentrations of DecaBDE were achieved in plasma and in milk with CO than with SPL. Furthermore, pups derived from dams treated with only SPL were lower in body weight, compared with those from dams treated with either CO, CO and DecaBDE, or SPL and DecaBDE. The study further shows that exposure to DecaBDE is relatively consistent across the dose range of 100 to 1000 mg/(kg . day) when administered in CO. PMID- 20581094 TI - Characterization of inhibitory effect of carbapenem antibiotics on the deconjugation of valproic acid glucuronide. AB - Serum concentrations of valproic acid (VPA) are markedly decreased by coadministration of carbapenem antibiotics (CBPMs). Although inhibition of deconjugation of VPA-glucuronide (VPA-G) to VPA by CBPMs has been proposed as one of the mechanisms to account for this drug-drug interaction, little information is available on the mode of inhibition. In the present study, we characterized the enzyme involved in the deconjugation of VPA-G by using human and rat liver cytosol. It is suggested that 1) deconjugation activity inhibited by CBPMs may be selective for VPA-G, 2) deconjugation of VPA-G may be mediated by enzyme(s) other than beta-glucuronidase, and 3) the irreversible inactivation may be responsible for the inhibition of deconjugation of VPA-G by CBPMs. Finally, the kinetic parameters for inactivation (K'(app) and k(inact)) were determined for four CBPMs of diverse structure from in vitro experiments. Based on the results of simulation analyses with these parameters and the degradation rate constant of the putative VPA-G deconjugation enzyme obtained from experiments using rats, it is probable that the deconjugation enzyme for VPA-G in the liver is rapidly and mostly inactivated by these CBPMs under clinical situations. PMID- 20581096 TI - Intradermal cytosine-phosphate-guanosine treatment reduces lung inflammation but induces IFN-gamma-mediated airway hyperreactivity in a murine model of natural rubber latex allergy. AB - Asthma and other allergic diseases are continuously increasing, causing considerable economic and sociologic burden to society. The hygiene hypothesis proposes that lack of microbial T helper (Th) 1-like stimulation during early childhood leads to increased Th2-driven allergic disorders later in life. Immunostimulatory cytosine-phosphate-guanosine (CpG)-oligodeoxynucleotide motifs are candidate molecules for immunotherapeutic studies, as they have been shown to shift the Th2 response toward the Th1 direction and reduce allergic symptoms. Using natural rubber latex (NRL)-induced murine model of asthma, we demonstrated that intradermal CpG administration with allergen reduced pulmonary eosinophilia, mucus production, and Th2-type cytokines, but unexpectedly induced airway hyperreactivity (AHR) to inhaled methacholine, one of the hallmarks of asthma. We found that induction in AHR was dependent on STAT4, but independent of STAT6 signaling. CpG treatment increased production of IFN-gamma in the airways and shifted the ratio of CD4(+):CD8(+) T cells toward CD8(+) dominance. By blocking soluble IFN-gamma with neutralizing antibody, AHR diminished and the CD4(+):CD8(+) ratio returned to CD4(+) dominance. These results indicate that increased production of IFN-gamma in the lungs may lead to severe side effects, such as enhancement of bronchial hyperreactivity to inhaled allergen. This finding should be taken into consideration when planning prophylaxis treatment of asthma with intradermal CpG injections. PMID- 20581095 TI - Airway epithelial NF-kappaB activation promotes allergic sensitization to an innocuous inhaled antigen. AB - Activation of NF-kappaB in airway epithelium is observed in allergic asthma and is induced by inhalation of numerous infectious and reactive substances. Many of the substances that activate NF-kappaB in the airway epithelium are also capable of acting as adjuvants to elicit antigen-specific sensitization to concomitantly inhaled protein, thereby circumventing the inherent bias of the lung to promote tolerance to innocuous antigens. We have used a transgenic mouse inducibly expressing a constitutively active mutant of the inhibitor of nuclear factor kappaB (IkappaB) kinase beta ((CA)IKKbeta) that activates NF-kappaB only in nonciliated airway epithelial cells to test whether activation of this intracellular signaling pathway in this specific cell type is sufficient to establish a pulmonary environment permissive to the development of allergic sensitization to inhaled protein. When airway epithelial (CA)IKKbeta was transiently expressed in antigen-naive mice only during initial inhalation of ovalbumin, the mice became allergically sensitized to the antigen. As a consequence, subsequent inhalation of ovalbumin alone led to an allergic asthma like response that included airway hyperresponsiveness to methacholine, eosinophilia, mucus expression, elevated serum levels of antigen-specific IgE and IgG1, and splenic CD4(+) T cells that secreted T helper type 2 and type 17 cytokines in response to in vitro antigen restimulation. Furthermore, CD11c(+) cells in the mediastinal lymph nodes (MLN) of (CA)IKKbeta-expressing mice displayed significantly elevated levels of activation markers. These data implicate airway epithelial NF-kappaB activation as a critical modulator of the adaptive immune response to inhaled antigens via the secretion of soluble mediators that affect the capacity of CD11c(+) cells to undergo maturation and promote antigen-specific allergic responses. PMID- 20581097 TI - c-Jun N-terminal kinase 1 promotes transforming growth factor-beta1-induced epithelial-to-mesenchymal transition via control of linker phosphorylation and transcriptional activity of Smad3. AB - Transforming growth factor (TGF)-beta1 is a key mediator of lung remodeling and fibrosis. Epithelial cells are both a source of and can respond to TGF-beta1 with epithelial-to-mesenchymal transition (EMT). We recently determined that TGF-beta1 induced EMT in lung epithelial cells requires the presence of c-Jun N-terminal kinase (JNK) 1. Because TGF-beta1 signals via Smad complexes, the goal of the present study was to determine the impact of JNK1 on phosphorylation of Smad3 and Smad3-dependent transcriptional responses in lung epithelial cells. Evaluation of JNK1-deficient lung epithelial cells demonstrated that TGF-beta1-induced terminal phosphorylation of Smad3 was similar, whereas phosphorylation of mitogen activated protein kinase sites in the linker regions of Smad3 was diminished, in JNK1-deficient cells compared with wild-type cells. In comparison to wild-type Smad3, expression of a mutant Smad3 in which linker mitogen-activated protein kinase sites were ablated caused a marked attenuation in JNK1 or TGF-beta1 induced Smad-binding element transcriptional activity, and expression of plasminogen activator inhibitor-1, fibronectin-1, high-mobility group A2, CArG box-binding factor-A, and fibroblast-specific protein-1, genes critical in the process of EMT. JNK1 enhanced the interaction between Smad3 and Smad4, which depended on linker phosphorylation of Smad3. Conversely, Smad3 with phosphomimetic mutations in the linker domain further enhanced EMT-related genes and proteins, even in the absence of JNK1. Finally, we demonstrated a TGF-beta1 induced interaction between Smad3 and JNK1. Collectively, these results demonstrate that Smad3 phosphorylation in the linker region and Smad transcriptional activity are directly or indirectly controlled by JNK1, and provide a putative mechanism whereby JNK1 promotes TGF-beta1-induced EMT. PMID- 20581098 TI - Genetic modification of airway progenitors after lentiviral gene delivery to the amniotic fluid of murine fetuses. AB - Lentiviral vectors with the firefly luciferase or enhanced green fluorescent protein (EGFP) transgenes were delivered to the amniotic fluid of murine fetuses at Embryonic Day (E) 14.5 or E16.5. Whole-body imaging of luciferase recipients after birth demonstrated transgene expression in the peritoneal and thoracic regions. Organ imaging showed luciferase expression in lung, skin, stomach, and/or intestine. Histological immunofluorescence analysis of EGFP recipients demonstrated that small clusters (<= three cells) of EGFP-positive epithelial cells were present in the large and small airways of recipients at up to 7 months (n = 11). There was no difference in the frequency of transgene expression in mice injected at E14.5 or E16.5 in respiratory or nonrespiratory organs. Analysis of the bronchoalveolar duct junctions on tissue sections of recipient mice identified multiple EGFP-positive epithelial cells. Cells coexpressing EGFP, Clara cell 10-kd protein, and surfactant protein C (SPC) were also found in lungs, consistent with the transduction of bronchoalveolar stem cells. Next, naphthalene lung injury in both luciferase and EGFP recipients was performed to determine whether transduced cells could contribute to tissue repair. In luciferase recipients, the whole-body luciferase signal increased 2- to 20-fold at 2 weeks after naphthalene treatment. Remarkably, immunohistological analysis of the lungs of EGFP recipients after lung injury repair demonstrated repopulation of airways with long stretches of EGFP-positive epithelial cells (n = 4). Collectively, these data demonstrate that lentiviral gene delivery to the amniotic fluid of murine fetuses genetically modifies long-lived epithelial progenitors capable of contributing to lung injury repair. PMID- 20581099 TI - Thrombospondin-1-deficient mice are not protected from bleomycin-induced pulmonary fibrosis. AB - Thrombospondin-1 (TSP-1) is an extracellular protein critical to normal lung homeostasis, and is reported to activate latent transforming growth factor-beta (TGF-beta). Because active TGF-beta is causally involved in lung fibrosis after bleomycin challenge, alterations in TSP-1 may be relevant to pulmonary fibrosis. We sought to determine the effects of TSP-1 deficiency on the susceptibility to bleomycin-induced pulmonary fibrosis in a murine model. Age-matched and sex matched C57BL/6 wild-type (WT) and TSP-1-deficient mice were treated twice weekly for 4 weeks with intraperitoneal bleomycin (0.035 U/g) or PBS, and were allowed to rest 1 week before being killed. Their lungs were inflated with PBS, fixed in formalin, paraffin-embedded, and sectioned. A certified veterinary pathologist blindly scored each slide for inflammation and fibrosis. Lungs were homogenized to obtain RNA and protein for the real-time RT-PCR analysis of connective tissue growth factor (CTGF) and collagen I, and for Western blotting to detect phospho Smad2, or total Smad2/3, respectively. In response to bleomycin treatment, measures of fibrosis and inflammation, along with CTGF and collagen I mRNA concentrations, were increased in TSP-1-deficient mice compared with WT mice. Notably, Smad 2/3 signaling was of equal strength in WT and TSP-1 knockout mice treated with bleomycin, suggesting that TSP-1 is not required for the activation of TGF-beta. These results demonstrate that TSP-1 deficiency does not protect mice from systemic bleomycin challenge, and that TSP-1 deficiency is associated with increased expression of lung collagen and CTGF. PMID- 20581100 TI - Effect of doxycycline on proliferation, MMP production, and adhesion in LAM related cells. AB - Matrix metalloproteinases (MMPs) have been implicated in lung cyst formation in lymphangioleiomyomatosis (LAM). As doxycycline inhibits MMP activity in vivo, some patients take doxycycline, as one report has suggested a possible benefit in LAM. However, there have been no randomized controlled clinical trials of doxycycline for LAM, and any mechanism of action is unclear. Here, we examine previously proposed mechanisms of actions. Cell proliferation and adhesion were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and Cytomatrix cell adhesion kits. Apoptosis was examined by TdT mediated dUTP nick end labeling (TUNEL) assay. MMP-2 expression was examined by quantitative real-time PCR and zymography in doxycycline-treated ELT3 cells and tumor growth using angiomyolipoma-derived tumor xenografts in nude mice. In ELT3 cells, >or=25 microg/ml doxycycline decreased proliferation, increased apoptosis, and caused a change in cell morphology associated with redistribution of actin stress filaments. Reduction in proliferation was also seen in human angiomyolipoma-derived cells. Cell adhesion to ECM proteins was decreased by doxycycline at 50 microg/ml and prevented detachment of already adherent cells. There was no effect of doxycycline on MMP-2 expression or activity in vitro. In the xenograft model, doxycycline (30 mg*kg(-1)*day(-1)) had no effect on tumor growth, final tumor weight, or tumor lysate MMP levels. Doxycycline at doses >or= 25 microg/ml inhibited cell proliferation and adhesion, possibly by a toxic effect. Doxycycline had no effect on MMP-2 expression or activity or tumor growth in the xenograft model. Any possible in vivo effect is unlikely to be mediated by MMP-2 or reduced cell proliferation. PMID- 20581101 TI - Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertension. AB - High-frequency echocardiography and high-field-strength magnetic resonance imaging (MRI) are new noninvasive methods for quantifying pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy (RVH). We compared these noninvasive methods of assessing the pulmonary circulation to the gold standard, cardiac catheterization (micromanometer-tipped catheters), in rats with monocrotaline-induced PAH and normal controls. Closed-chest, Sprague-Dawley rats were anesthetized with inhaled isoflurane (25 monocrotaline, 6 age-matched controls). Noninvasive studies used 37.5-MHz ultrasound (Vevo 770; VisualSonics) or a 9.4-T MRI (Bruker BioSpin). Catheterization used a 1.4-F micromanometer tipped Millar catheter and a thermodilution catheter to measure cardiac output (CO). We compared noninvasive measures of pulmonary artery (PA) pressure (PAP) using PA acceleration time (PAAT) and CO, using the geometric PA flow method and RV free wall (RVFW) thickness/mass with cardiac catheterization and/or autopsy. Blinded operators performed comparisons using each method within 2 days of another. In a subset of rats with monocrotaline PAH, weekly echocardiograms, catheterization, and autopsy data assessed disease progression. Heart rate was similar during all studies (>323 beats/min). PAAT shortened, and the PA flow envelope displayed systolic "notching," reflective of downstream vascular remodeling/stiffening, within 3 wk of monocrotaline. MRI and echocardiography measures of PAAT were highly correlated (r(2) = 0.87) and were inversely proportional to invasive mean PAP (r(2) = 0.72). Mean PAP by echocardiography was estimated as 58.7 - (1.21 x PAAT). Invasive and noninvasive CO measurement correlated well (r(2) >or= 0.75). Noninvasive measures of RVFW thickness/mass correlated well with postmortem measurements. We conclude that high-resolution echocardiography and MRI accurately determine CO, PAP, and RV thickness/mass, offering similar results as high-fidelity right heart catheterization and autopsy, and that PAAT accurately estimates PAP and permits serial monitoring of experimental PAH. These tools are useful for assessment of the rodent pulmonary circulation and RVH. PMID- 20581103 TI - Pre-clinical diabetic cardiomyopathy: prevalence, screening, and outcome. AB - AIMS: Diabetic cardiomyopathy, characterized by left ventricular (LV) dysfunction and LV hypertrophy independent of myocardial ischaemia and hypertension, could contribute to the increased life-time risk of congestive heart failure seen in patients with diabetes. We assessed prospectively the prevalence, effectiveness of screening methods [brain natriuretic peptide (BNP) and C-reactive protein in combination with clinical parameters], and outcome of pre-clinical diabetic cardiomyopathy. METHODS AND RESULTS: We studied 100 adults (mean age 57.4 +/- 10.2 years, 44% females) with diabetes and no previous evidence of structural heart disease. By echocardiography, diabetic cardiomyopathy was present in 48% of patients. Screening with combinations of clinical parameters (gender, systolic blood pressure, and body mass index), but not BNP, resulted in high negative predictive values for diabetic cardiomyopathy. During a mean follow-up of 48.5 +/ 9.0 months, in the groups with and without diabetic cardiomyopathy, 12.5 vs. 3.9% (P < 0.2) patients died or experienced cardiovascular events and 37.5 vs. 9.6% (P < 0.002) had a deterioration in NYHA functional class. Overall event-free survival was 54 vs. 87% (P = 0.001) in the groups with and without diabetic cardiomyopathy, respectively. Brain natriuretic peptide was an independent predictor of events [odds ratio 3.5 (1.1-10.9), P = 0.02]. CONCLUSION: Pre clinical diabetic cardiomyopathy is common. Screening with combinations of simple clinical parameters, but not BNP, can be useful to identify those patients needing further evaluation. Patients with pre-clinical diabetic cardiomyopathy are at increased risk for functional deterioration and possibly cardiovascular events during follow-up. Brain natriuretic peptide was shown to be an independent predictor of future events. PMID- 20581102 TI - Functional consequences of the collagen/elastin switch in vascular remodeling in hyperhomocysteinemic wild-type, eNOS-/-, and iNOS-/- mice. AB - A decrease in vascular elasticity and an increase in pulse wave velocity in hyperhomocysteinemic (HHcy) cystathionine-beta-synthase heterozygote knockout (CBS(-/+)) mice has been observed. Nitric oxide (NO) is a potential regulator of matrix metalloproteinase (MMP) activity in MMP-NO-tissue inhibitor of metalloproteinase (TIMP) inhibitory tertiary complex. However, the contribution of the nitric oxide synthase (NOS) isoforms eNOS and iNOS in the activation of latent MMP is unclear. We hypothesize that the differential production of NO contributes to oxidative stress and increased oxidative/nitrative activation of MMP, resulting in vascular remodeling in response to HHcy. The overall goal is to elucidate the contribution of the NOS isoforms, endothelial and inducible, in the collagen/elastin switch. Experiments were performed on six groups of animals [wild-type (WT), eNOS(-/-), and iNOS(-/-) with and without homocysteine (Hcy) treatment (0.67 g/l) for 8-12 wk]. In vivo echograph was performed to assess aortic timed flow velocity for indirect compliance measurement. Histological determination of collagen and elastin with trichrome and van Gieson stains, respectively, was performed. In situ measurement of superoxide generation using dihydroethidium was used. Differential expression of eNOS, iNOS, nitrotyrosine, MMP-2 and -9, and elastin were measured by quantitative PCR and Western blot analyses. The 2% gelatin zymography was used to assess MMP activity. The increase in O(2)(-) and robust activity of MMP-9 in eNOS(-/-), WT+Hcy, and eNOS(-/-)+Hcy was accompanied by the gross disorganization and thickening of the ECM along with extensive collagen deposition and elastin degradation (collagen/elastin switch) resulting in a decrease in aortic timed flow velocity. Results show that an increase in iNOS activity is a key contributor to HHcy-mediated collagen/elastin switch and resulting decline in aortic compliance. PMID- 20581104 TI - ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis. AB - Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 +/- 10.5 years; BMI, 23.9 +/- 3.5 kg/m(2)). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant [n = 614; -0.11 mmol/l (95% CI, range: -0.20 to -0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best. PMID- 20581105 TI - Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population. AB - Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors. PMID- 20581107 TI - Functional genomics of physiological plasticity and local adaptation in killifish. AB - Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation. PMID- 20581108 TI - Cytogenetics meets phylogenetics: a review of karyotype evolution in diprotodontian marsupials. AB - We have used a combined approach of phylogenetics and cytogenetics to describe karyotype evolution in Diprotodontia. Molecular relationships of diprotodontian marsupials have been clarified using a concatenation of 5 nuclear gene sequences from multiple exemplars of all extant genera. Our well-resolved phylogenetic tree has been used as a basis for understanding chromosome evolution both within this Order, as well as in marsupials in general. It is clear that the ancestral marsupial karyotype comprised 14 relatively large chromosomes of the form retained relatively unchanged in caenolestids, microbiotherians, peramelemorphians, vombatids, and pygmy possums. Four pericentric inversions occurred in the ancestral dasyuromorphian (chromosomes 1, 2, 4, and 6) and a different 4 in the ancestral didelphimorphian (chromosomes 1, 3, 5 and 6). Within Diprotodontia, although the ancestral marsupial karyotype has been retained in some families such as the extant wombats and pygmy possums, there have been major karytoypic repatternings early in the evolution of others. Chromosome rearrangements in diprotodontia include centric fissions and fusions, translocations, and centromere shifts. Karyotypic changes are discussed in the context of current hypotheses concerning centromeres, chromosomal fragile sites, and mobile elements in marsupials and the probable repeated involvement of these elements in karyotypic restructuring. PMID- 20581109 TI - Historical perspectives on literacy in early childhood. AB - PURPOSE: To more fully understand current trends in preliteracy research, as well as controversies that continue to surround best teaching practices, it is essential to have an understanding of the historical evolution of ideas and practices relevant to preparing young children for learning to read. METHOD: Several interrelated historical movements relevant to placing current research and practices related to preliteracy development in context are reviewed. These ideas play out in the interrelated and changing ideas regarding the role of the family in children's literacy development, as well as in the appropriate curriculum for preschoolers. Both historical reviews and original documents pertinent to the various historical trends are used to provide the current synthesis. CONCLUSIONS: The roots of most current practices during, and controversies regarding, the preliteracy period of development can be traced to a variety of different historical events, as well as to prominent philosophers and educators. Familiarity with these events, philosophers, and educators provides the perspective needed to effectively evaluate new information and approaches that come to the forefront, or that are currently being practiced by different groups or in different settings. PMID- 20581110 TI - Examining dynamic visual scene displays: implications for arranging and teaching symbol selection. AB - PURPOSE: Evidence supports using visual scene displays (VSDs) with young children using speech-generating devices. This study examined initial and subsequent performance during VSD use by children age 24-27 and 33-36 months to explore child characteristics that may relate to navigational skill differences. METHOD: Children located 9 vocabulary items using a dynamic VSD. Tests of mean difference and analyses of variance were both completed to examine within- and between-age group performance for accuracy and latency across 3 time points: at initial exposure, at criterion, and at a 2-week maintenance session for each of 2 linked navigational pages. RESULTS: Results indicated that, at initial exposure, older participants' symbol selections were significantly more accurate and significantly faster when navigating through each page of a 2-page dynamic VSD. Results also indicated that though younger participants required significantly more sessions to achieve mastery, when the effects of practice and language comprehension were controlled, performance differences between age groups were not found when maintenance was evaluated. CONCLUSIONS: Older children perform better than younger children on initial opportunities. However, younger children learn to use VSDs in relatively few instructional opportunities, suggesting that VSDs can be used with children as young as 2 years of age. PMID- 20581111 TI - Clostridiolysin S, a post-translationally modified biotoxin from Clostridium botulinum. AB - Through elaboration of its botulinum toxins, Clostridium botulinum produces clinical syndromes of infant botulism, wound botulism, and other invasive infections. Using comparative genomic analysis, an orphan nine-gene cluster was identified in C. botulinum and the related foodborne pathogen Clostridium sporogenes that resembled the biosynthetic machinery for streptolysin S, a key virulence factor from group A Streptococcus responsible for its hallmark beta hemolytic phenotype. Genetic complementation, in vitro reconstitution, mass spectral analysis, and plasmid intergrational mutagenesis demonstrate that the streptolysin S-like gene cluster from Clostridium sp. is responsible for the biogenesis of a novel post-translationally modified hemolytic toxin, clostridiolysin S. PMID- 20581112 TI - Toward a quantitative modeling of the synthesis of the pectate lyases, essential virulence factors in Dickeya dadantii. AB - A dynamic mathematical model has been developed and validated to describe the synthesis of pectate lyases (Pels), the major virulence factors in Dickeya dadantii. This work focuses on the simultaneous modeling of the metabolic degradation of pectin by Pel enzymes and the genetic regulation of pel genes by 2 keto-3-deoxygluconate (KDG), a catabolite product of pectin that inactivates KdgR, one of the main repressors of pel genes. This modeling scheme takes into account the fact that the system is composed of two time-varying compartments: the extracellular medium, where Pel enzymes cleave pectin into oligomers, and the bacterial cytoplasm where, after internalization, oligomers are converted to KDG. Using the quasi-stationary state approximations, the model consists of some nonlinear differential equations for which most of the parameters could be estimated from the literature or from independent experiments. The few remaining unknown parameters were obtained by fitting the model equations against a set of Pel activity data. Model predictions were verified by measuring the time courses of bacterial growth, Pel production, pel mRNA accumulation, and pectin consumption under various growth conditions. This work reveals that pectin is almost totally consumed before the burst of Pel production. This paradoxical behavior can be interpreted as an evolutionary strategy to control the diffusion process so that as soon as a small amount of pectin is detected by the bacteria in its surroundings, it anticipates more pectin to come. The model also predicts the possibility of bistable steady states in the presence of constant pectin compounds. PMID- 20581113 TI - Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF 1alpha subunit via type I activin-like receptor kinase receptor signaling. AB - Toxoplasma gondii is an intracellular protozoan parasite that can cause devastating disease in fetuses and immune-compromised individuals. We previously reported that the alpha subunit of the host cell transcription factor, hypoxia inducible factor-1 (HIF-1), is up-regulated by infection and necessary for Toxoplasma growth. Under basal conditions, HIF-1alpha is constitutively expressed but rapidly targeted for proteasomal degradation after two proline residues are hydroxylated by a family of prolyl hydroxylases (PHDs). The PHDs are alpha ketoglutarate-dependent dioxygenases that have low K(m) values for oxygen, making them important cellular oxygen sensors. Thus, when oxygen levels decrease, HIF 1alpha is not hydroxylated, and HIF-1 is activated. How Toxoplasma activates HIF 1 under normoxic conditions remains unknown. Here, we report that Toxoplasma infection increases HIF-1alpha stability by preventing HIF-1alpha prolyl hydroxylation. Infection significantly decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1alpha. The effects of Toxoplasma on HIF 1alpha abundance and prolyl hydroxylase activity require activin-like receptor kinase signaling. Finally, parasite growth is severely diminished when signaling from this family of receptors is inhibited. Together, these data indicate that PHD2 is a key host cell factor for T. gondii growth and represent a novel mechanism by which a microbial pathogen subverts host cell signaling and transcription to establish its replicative niche. PMID- 20581114 TI - The interplay of proton, electron, and metabolite supply for photosynthetic H2 production in Chlamydomonas reinhardtii. AB - To obtain a detailed picture of sulfur deprivation-induced H(2) production in microalgae, metabolome analyses were performed during key time points of the anaerobic H(2) production process of Chlamydomonas reinhardtii. Analyses were performed using gas chromatography coupled to mass spectrometry (GC/MS), two dimensional gas chromatography combined with time-of-flight mass spectrometry (GCxGC-TOFMS), lipid and starch analysis, and enzymatic determination of fermentative products. The studies were designed to provide a detailed metabolite profile of the solar Bio-H(2) production process. This work reports on the differential analysis of metabolic profiles of the high H(2)-producing strain Stm6Glc4 and the wild-type cc406 (WT) before and during the H(2) production phase. Using GCxGC-TOFMS analysis the number of detected peaks increased from 128 peaks, previously detected by GC/MS techniques, to ~1168. More detailed analysis of the anaerobic H(2) production phase revealed remarkable differences between wild-type and mutant cells in a number of metabolic pathways. Under these physiological conditions the WT produced up to 2.6 times more fatty acids, 2.2 times more neutral lipids, and up to 4 times more fermentation products compared with Stm6Glc4. Based on these results, specific metabolic pathways involving the synthesis of fatty acids, neutral lipids, and fermentation products during anaerobiosis in C. reinhardtii have been identified as potential targets for metabolic engineering to further enhance substrate supply for the hydrogenase(s) in the chloroplast. PMID- 20581115 TI - Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains. AB - Ganglioside GD3 is widely expressed in human malignant melanoma cell lines and tumors. Previously, we reported that GD3+ cells show stronger tyrosine phosphorylation of focal adhesion kinase (FAK), p130(Cas), and paxillin when treated with fetal calf serum than GD3- cells. In this study, we analyzed the changes in the signals mediated by the interaction between integrins and extracellular matrices (ECM) to clarify how GD3 enhances cell signals in the vicinity of the cell membrane. An adhesion assay with a real time cell electronic sensing system revealed that GD3+ cells had stronger adhesion to all extracellular matrices examined. In particular, GD3+ cells attached more strongly to collagen type I and type IV than controls. Correspondingly, they showed stronger tyrosine phosphorylation of FAK and paxillin during adhesion to collagen type I. In the floating pattern of detergent extracts, a high level of integrin beta1 was found in glycolipid-enriched microdomain (GEM)/rafts in GD3+ cells before adhesion, whereas a smaller amount of integrin beta1 was detected in the GEM/rafts of controls. Some phosphorylated forms of FAK as well as total FAK were found in GEM/rafts during cell adhesion only in GD3+ cells. Another signal consisting of integrin-linked kinase/Akt was also activated during adhesion more strongly in GD3+ cells than in controls. In double stained GD3+ cells, GD3 and integrin beta1 co-localized at the focal adhesion with a punctate pattern. All these results suggested that integrins assembled and formed a cluster in GEM/rafts, leading to the enhanced signaling and malignant properties under GD3 expression. PMID- 20581116 TI - RecO-mediated DNA homology search and annealing is facilitated by SsbA. AB - Bacillus subtilis RecO plays a central role in recombinational repair and genetic recombination by (i) stimulating RecA filamentation onto SsbA-coated single stranded (ss) DNA, (ii) modulating the extent of RecA-mediated DNA strand exchange and (iii) promoting annealing of complementary DNA strands. Here, we report that RecO-mediated strand annealing is facilitated by cognate SsbA, but not by a heterologous one. Analysis of non-productive intermediates reveals that RecO interacts with SsbA-coated ssDNA, resulting in transient ternary complexes. The self-interaction of ternary complexes via RecO led to the formation of large nucleoprotein complexes. In the presence of homology, SsbA, at the nucleoprotein, removes DNA secondary structures, inhibits spontaneous strand annealing and facilitates RecO loading onto SsbA-ssDNA complex. RecO relieves SsbA inhibition of strand annealing and facilitates transient and random interactions between homologous naked ssDNA molecules. Finally, both proteins lose affinity for duplex DNA. Our results provide a mechanistic framework for rationalizing protein release and dsDNA zippering as coordinated events that are crucial for RecA independent plasmid transformation. PMID- 20581117 TI - All-codon scanning identifies p53 cancer rescue mutations. AB - In vitro scanning mutagenesis strategies are valuable tools to identify critical residues in proteins and to generate proteins with modified properties. We describe the fast and simple All-Codon Scanning (ACS) strategy that creates a defined gene library wherein each individual codon within a specific target region is changed into all possible codons with only a single codon change per mutagenesis product. ACS is based on a multiplexed overlapping mutagenesis primer design that saturates only the targeted gene region with single codon changes. We have used ACS to produce single amino-acid changes in small and large regions of the human tumor suppressor protein p53 to identify single amino-acid substitutions that can restore activity to inactive p53 found in human cancers. Single-tube reactions were used to saturate defined 30-nt regions with all possible codon changes. The same technique was used in 20 parallel reactions to scan the 600-bp fragment encoding the entire p53 core domain. Identification of several novel p53 cancer rescue mutations demonstrated the utility of the ACS approach. ACS is a fast, simple and versatile method, which is useful for protein structure-function analyses and protein design or evolution problems. PMID- 20581118 TI - In polycistronic Qbeta RNA, single-strandedness at one ribosome binding site directly affects translational initiations at a distal upstream cistron. AB - In Qbeta RNA, sequestering the coat gene ribosome binding site in a putatively strong hairpin stem structure eliminated synthesis of coat protein and activated protein synthesis from the much weaker maturation gene initiation site, located 1300 nucleotides upstream. As the stability of a hairpin stem comprising the coat gene Shine-Dalgarno site was incrementally increased, there was a corresponding increase in translation of maturation protein. The effect of the downstream coat gene ribosome binding sequence on maturation gene expression appeared to have occurred only in cis and did not require an AUG start codon or initiation of coat protein synthesis. In all cases, no structural reorganization was predicted to occur within Qbeta RNA. Our results suggest that protein synthesis from a relatively weak translational initiation site is greatly influenced by the presence or absence of a stronger ribosome binding site located elsewhere on the same RNA molecule. The data are consistent with a mechanism in which multiple ribosome binding sites compete in cis for translational initiations as a means of regulating protein synthesis on a polycistronic messenger RNA. PMID- 20581119 TI - Rural primary care in Greece: working under limited resources. AB - OBJECTIVE: Establishing sufficient primary health-care services in rural areas is of high interest in developing health systems. The objective of the present study was to describe the state of rural health services, in terms of personnel and equipment, in rural primary care settings in Greece. DESIGN: A questionnaire was sent to all Greek rural settings (RS) (practices) twice during 2007. The questionnaire included questions about the number of doctors in the practice, their specialty, presence of a nurse, population served and average distance from the regional Health Center and hospital. It also included questions about the average number of consultations per day, home visits, maintenance of medical records and medical equipment. SETTING: Rural primary care settings in Greece. PARTICIPANTS: Doctors serving primary care needs during the second half of 2007. INTERVENTION: s) None. MAIN OUTCOME MEASURE: s) Data concerning staffing, function and available equipment of the RS have been collected. RESULTS: Five hundred eighty-two (40.9%) of the rural practitioners replied. Twenty-nine percent of the participants were general practitioners (GPs). Doctors reported average population of responsibility of 2263 citizens and a regular average of 26 consultations per day. A nurse was present in 174 RS (29.5%). Medical records of any form were kept in only 36% of the RS. GPs were more prone to maintain patients files compared with non-specialized doctors. Essential equipment proved to be limited in the majority of the RS. CONCLUSIONS: Rural practices in Greece report shortages of medical staff (GPs), nursing staff and equipment. PMID- 20581120 TI - Emergence of linezolid-resistant coagulase-negative Staphylococcus in a cancer centre linked to increased linezolid utilization. AB - OBJECTIVES: The prevalence of linezolid-resistant coagulase-negative Staphylococcus (CoNS) in the MD Anderson Cancer Center rose from 0.6% in 2007 to 5.5% in 2009. The aim of our study was to analyse the relationship between linezolid use and an outbreak of linezolid-resistant CoNS. PATIENTS AND METHODS: We retrospectively identified 27 infection or colonization events. Eleven isolates were available for supplemental investigation; species identification, clonal relatedness and linezolid resistance mutation analysis. The medical records of the affected patients were reviewed and linezolid utilization data were obtained from the pharmacy. RESULTS: Available isolates were confirmed as clonally related Staphylococcus epidermidis. Partial 23S rRNA gene sequencing found a G2576T mutation in all of the isolates tested. All patients received linezolid within 3 months prior to an event. Patients without a prior hospitalization had a longer time from admission to event; 29 versus 3.5 days (P = 0.002). The outbreak was preceded by a 51% increase in inpatient linezolid utilization and 64% of affected patients belonged to the leukaemia service, which had a utilization rate 3.1 times that of the other services (95% confidence interval: 2.96-3.23). CONCLUSIONS: Increased linezolid utilization preceded the appearance of a linezolid-resistant CoNS clone. Patients probably acquired the clonal strain nosocomially, given the longer time from admission to event among patients with no previous admission to the MD Anderson Cancer Center. Linezolid administration then selected this strain, since all patients received linezolid prior to an event. A linezolid utilization rate of >or=13 defined daily doses/100 patient-days was similar to that reported in two other outbreaks and may be the threshold required to generate an outbreak. PMID- 20581121 TI - Antibiotic use in 530 French hospitals: results from a surveillance network at hospital and ward levels in 2007. AB - OBJECTIVES: Antibiotic use in French hospitals is among the highest in Europe. A study was carried out to describe antibiotic consumption for inpatients at hospital and at ward levels. METHODS: Data were voluntarily collected retrospectively by 530 hospitals accounting for approximately 40 million patient days (PD) on the following: antibacterials for systemic use [J01 class of the WHO Anatomical Therapeutic Chemical (ATC) classification, defined daily doses (DDD) system, 2007], rifampicin and oral imidazole derivatives, expressed in number of DDD and number of PD in 2007. Consumption was expressed in DDD/1000 PD. RESULTS: Median antibiotic use ranged from 60 DDD/1000 PD in long-term care (LTC) and psychiatric hospitals to 633 DDD/1000 PD in teaching hospitals. Penicillins and beta-lactamase inhibitors combinations were the most frequently used antibiotics, accounting for 26% of total use in cancer hospitals to 40% in LTC/psychiatric hospitals. Glycopeptides and carbapenems were mostly used in cancer and teaching hospitals. Level of consumption and pattern of use differed according to clinical ward from 60 DDD/1000 PD in psychiatric wards up to 1466 DDD/1000 PD in intensive care units (ICUs). In medicine, surgery, ICU and rehabilitation wards, fluoroquinolones accounted for 13%-19% of the total use. CONCLUSIONS: This multicentre survey provided detailed information on antibiotic use in a large sample of hospitals and wards, allowing relevant comparisons and benchmarking. Analysis of consumption at the ward level should help hospitals to target practice audits to improve antibiotic use. PMID- 20581122 TI - Recombinant protease inhibitors for herbivore pest control: a multitrophic perspective. AB - Protease inhibitors are a promising complement to Bt toxins for the development of insect-resistant transgenic crops, but their limited specificity against proteolytic enzymes and the ubiquity of protease-dependent processes in living organisms raise questions about their eventual non-target effects in agroecosystems. After a brief overview of the main factors driving the impacts of insect-resistant transgenic crops on non-target organisms, the possible effects of protease inhibitors are discussed from a multitrophic perspective, taking into account not only the target herbivore proteases but also the proteases of other organisms found along the trophic chain, including the plant itself. Major progress has been achieved in recent years towards the design of highly potent broad-spectrum inhibitors and the field deployment of protease inhibitor expressing transgenic plants resistant to major herbivore pests. A thorough assessment of the current literature suggests that, whereas the non-specific inhibitory effects of recombinant protease inhibitors in plant food webs could often be negligible and their 'unintended' pleiotropic effects in planta of potential agronomic value, the innocuity of these proteins might always remain an issue to be assessed empirically, on a case-by-case basis. PMID- 20581123 TI - Brachytic2/ZmABCB1 functions in IAA export from intercalary meristems. AB - Dwarfism traits in Zea mays are regulated by multiple factors including the hormone auxin. Dwarf brachytic2 (br2) mutants harbour lesions in the gene encoding an orthologue of Arabidopsis thaliana ABCB1 which functions in auxin efflux out of meristematic regions in the shoot and root. br2 mesocotyls and coleoptiles exhibit reduced auxin transport. However, the dwarf stature of br2 derives from shortened lower internodes whilst the upper portion of the plant is completely normal. As such, it is counter-intuitive to attribute br2 dwarfism exclusively to reduced auxin export out of the shoot apex. Arabidopsis abcb1 mutants exhibit only minor reductions in auxin transport and plant height unless combined with mutations in the ABCB19 auxin transporter. Phylogenetic modelling analysis excludes the possibility that BR2 is more closely related to ABCB19 which has three more closely related orthologues in maize. BR2 is expressed in nodal meristems, and analyses of auxin transport and content indicate that BR2 function in these grass-specific tissues is analogous to ABCB1 function in the shoot and root apex of Arabidopsis. These results indicate that ABCB1/BR2 function is conserved between dicots and monocots, but also suggests that this function must be understood in the context of the segmental organization of grass plants. PMID- 20581124 TI - Sequestration of auxin by the indole-3-acetic acid-amido synthetase GH3-1 in grape berry (Vitis vinifera L.) and the proposed role of auxin conjugation during ripening. AB - In fleshy fruit, levels of indole-3-acetic acid (IAA), the most abundant auxin, decline towards the onset of ripening. The application of auxins to immature fruit can delay the ripening processes. However, the mechanisms by which the decrease in endogenous IAA concentrations and the maintenance of low auxin levels in maturing fruit are achieved remain elusive. The transcript of a GH3 gene (GH3 1), encoding for an IAA-amido synthetase which conjugates IAA to amino acids, was detected in grape berries (Vitis vinifera L.). GH3-1 expression increased at the onset of ripening (veraison), suggesting that it might be involved in the establishment and maintenance of low IAA concentrations in ripening berries. Furthermore, this grapevine GH3 gene, responded positively to the combined application of abscisic acid and sucrose and to ethylene, linking it to the control of ripening processes. Levels of IAA-aspartic acid (IAA-Asp), an in vitro product of recombinant GH3-1, rose after veraison and remained high during the following weeks of the ripening phase when levels of free IAA were low. A similar pattern of changes in free IAA and IAA-Asp levels was detected in developing tomatoes (Solanum lycopersicum Mill.), where low concentrations of IAA and an increase in IAA-Asp concentrations coincided with the onset of ripening in this climacteric fruit. Since IAA-Asp might be involved in IAA degradation, the GH3 catalysed formation of this conjugate at, and after, the onset of ripening could represent a common IAA inactivation mechanism in climacteric and non-climacteric fruit which enables ripening. PMID- 20581125 TI - Exogenously induced expression of ethylene biosynthesis, ethylene perception, phospholipase D, and Rboh-oxidase genes in broccoli seedlings. AB - In higher plants, copper ions, hydrogen peroxide, and cycloheximide have been recognized as very effective inducers of the transcriptional activity of genes encoding the enzymes of the ethylene biosynthesis pathway. In this report, the transcriptional patterns of genes encoding the 1-aminocyclopropane-1-carboxylate synthases (ACSs), 1-aminocyclopropane-1-carboxylate oxidases (ACOs), ETR1, ETR2, and ERS1 ethylene receptors, phospholipase D (PLD)-alpha1, -alpha2, -gamma1, and delta, and respiratory burst oxidase homologue (Rboh)-NADPH oxidase-D and -F in response to these inducers in Brassica oleracea etiolated seedlings are shown. ACS1, ACO1, ETR2, PLD-gamma1, and RbohD represent genes whose expression was considerably affected by all of the inducers used. The investigations were performed on the seedlings with (i) ethylene insensitivity and (ii) a reduced level of the PLD-derived phosphatidic acid (PA). The general conclusion is that the expression of ACS1, -3, -4, -5, -7, and -11, ACO1, ETR1, ERS1, and ETR2, PLD gamma 1, and RbohD and F genes is undoubtedly under the reciprocal cross-talk of the ethylene and PA(PLD) signalling routes; both signals affect it in concerted or opposite ways depending on the gene or the type of stimuli. The results of these studies on broccoli seedlings are in agreement with the hypothesis that PA may directly affect the ethylene signal transduction pathway via an inhibitory effect on CTR1 (constitutive triple response 1) activity. PMID- 20581127 TI - Rugby union injuries in Scottish schools. AB - BACKGROUND: Rugby union is the most popular worldwide collision sport, yet concerns have been raised regarding the safety of the sport due to the physical, high impact nature and an increasing number of injuries. METHODS: A prospective, cohort study of the incidence, pattern and severity of injuries in rugby players in six Scottish schools during the second half of the 2008-09 season. Definition of injury and severity of injury were taken from International Rugby Board (IRB) consensus guidelines. Injury report forms and exposure data for match play were completed by a nominated staff member. RESULTS: Four hundred and seventy consent forms with survey information were returned. Of 37 rugby injuries in the study, 11 occurred during training. Head and face were the most injured body part and sprain/ligament injury the most common injury. Twenty injuries required attendance at Accident & Emergency with one admission. The tackle was the commonest phase of play causing injury. In the 193 matches played, the injury incidence during the match play was 10.8 injuries per 1000 player hours. CONCLUSIONS: This study confirms the feasibility of collecting relevant injury data in schools rugby in Scotland. The findings are consistent with other studies with respect to incidence and profile of injuries sustained. PMID- 20581126 TI - Mutagenicity of acrylamide and glycidamide in the testes of big blue mice. AB - Acrylamide (AA) is an industrial chemical, a by-product of fried starchy foods, and a mutagen and rodent carcinogen. It can also cause damage during spermatogenesis. In this study, we investigated whether AA and its metabolite glycidamide (GA) induce mutagenic effects in the germ cells of male mice. Male Big Blue transgenic mice were administered 1.4 or 7.0mM of AA or GA in the drinking water for up to 4 weeks. Testicular cII mutant frequency (MF) was determined 3 weeks after the last treatment, and the types of the mutations in the cII gene were analyzed by DNA sequencing. The testes cII MFs in mice treated with either the low or high exposure concentrations of AA and GA were increased significantly. There was no significant difference in the cII MFs between AA and GA at the low exposure concentration. The mutation spectra in mice treated with AA (1.4mM) or GA (both 1.4 and 7.0mM) differed significantly from those of controls, but there were no significant differences in mutation patterns between AA and GA treatments. Comparison of the mutation spectra between testes and livers showed that the spectra differed significantly between the two tissues following treatment with AA or GA, whereas the mutation spectra in the two tissues from control mice were similar. These results suggest that AA possesses mutagenic effects on testes by virtue of its metabolism to GA, possibly targeting spermatogonial stem cells, but possibly via different pathways when compared mutations in liver. PMID- 20581128 TI - Predictive factors in in vitro fertilization (IVF): a systematic review and meta analysis. AB - BACKGROUND: Various models have been developed for the prediction of pregnancy after in vitro fertilization (IVF). These models differ from one another in the predictors they include. We performed a systematic review and meta-analysis to identify the most relevant predictors for success in IVF. METHODS: We systematically searched MEDLINE and EMBASE for studies evaluating IVF/ICSI outcome. Studies were included if they reported an unconditional odds ratio (OR) or whenever one could be calculated for one or more of the following factors: age, type of infertility, indication, duration of infertility, basal FSH, number of oocytes, fertilization method, number of embryos transferred and embryo quality. RESULTS: Fourteen studies were identified. A summary OR could be calculated for five factors. We found negative associations between pregnancy and female age [OR: 0.95, 95% confidence interval (CI): 0.94-0.96], duration of subfertility (OR: 0.99, 95% CI: 0.98-1.00) and basal FSH (OR: 0.94, 95% CI: 0.88 1.00). We found a positive association with number of oocytes (OR 1.04, 95% CI: 1.02-1.07). Better embryo quality was associated with higher pregnancy chances. No significant association was found for the type of infertility and fertilization method. A summary OR for IVF indication and number of embryos transferred could not be calculated, because studies reporting on these used different reference categories. CONCLUSIONS: Female age, duration of subfertility, bFSH and number of oocytes, all reflecting ovarian function, are predictors of pregnancy after IVF. Better quality studies are necessary, especially studies that focus on embryo factors that are predictive of success in IVF. PMID- 20581129 TI - Structure of the three-way helical junction of the hepatitis C virus IRES element. AB - The hepatitis C virus internal ribosome entry site (IRES) element contains a three-way junction that is important in the overall RNA conformation, and for its role in the internal initiation of translation. The junction also illustrates some important conformational principles in the folding of three-way helical junctions. It is formally a 3HS(4) junction, with the possibility of two alternative stacking conformers. However, in principle, the junction can also undergo two steps of branch migration that would form 2HS(1)HS(3) and 2HS(2)HS(2) junctions. Comparative gel electrophoresis and ensemble fluorescence resonance energy transfer (FRET) studies show that the junction is induced to fold by the presence of Mg(2+) ions in low micromolar concentrations, and suggest that the structure adopted is based on coaxial stacking of the two helices that do not terminate in a hairpin loop (i.e., helix IIId). Single-molecule FRET studies confirm this conclusion, and indicate that there is no minor conformer present based on an alternative choice of helical stacking partners. Moreover, analysis of single-molecule FRET data at an 8-msec resolution failed to reveal evidence for structural transitions. It seems probable that this junction adopts a single conformation as a unique and stable fold. PMID- 20581130 TI - In vitro incorporation of nonnatural amino acids into protein using tRNA(Cys) derived opal, ochre, and amber suppressor tRNAs. AB - Amber suppressor tRNAs are widely used to incorporate nonnatural amino acids into proteins to serve as probes of structure, environment, and function. The utility of this approach would be greatly enhanced if multiple probes could be simultaneously incorporated at different locations in the same protein without other modifications. Toward this end, we have developed amber, opal, and ochre suppressor tRNAs derived from Escherichia coli, and yeast tRNA(Cys) that incorporate a chemically modified cysteine residue with high selectivity at the cognate UAG, UGA, and UAA stop codons in an in vitro translation system. These synthetic tRNAs were aminoacylated in vitro, and the labile aminoacyl bond was stabilized by covalently attaching a fluorescent dye to the cysteine sulfhydryl group. Readthrough efficiency (amber > opal > ochre) was substantially improved by eRF1/eRF3 inhibition with an RNA aptamer, thus overcoming an intrinsic hierarchy in stop codon selection that limits UGA and UAA termination suppression in higher eukaryotic translation systems. This approach now allows concurrent incorporation of two different modified amino acids at amber and opal codons with a combined apparent readthrough efficiency of up to 25% when compared with the parent protein lacking a stop codon. As such, it significantly expands the possibilities for incorporating nonnative amino acids for protein structure/function studies. PMID- 20581132 TI - Stroke thrombolysis in England, Wales and Northern Ireland: how much do we do and how much do we need? AB - BACKGROUND: Data are limited on the proportion of stroke patients nationally appropriate for thrombolysis either within the 3 h time window or the recently tested 4.5 h. This information is important for the redesign of services. METHODS: Data on case mix, eligibility for thrombolysis, treatment and outcomes were extracted from the National Sentinel Stroke 2008 Audit dataset. This contains retrospective data on up to 60 consecutive stroke admissions from each acute hospital in England, Wales and Northern Ireland between 1 April and 30 June 2008. FINDINGS: All relevant hospitals participated, submitting data on 11,262 acute stroke patients. 2118 patients arrived within 2 h and 2596 within 3 h of the onset of symptoms and 587 people were already in hospital. Therefore, 28% (3183) were potentially eligible for thrombolysis based on a 3 h time criterion. Of these, 1914 were under 80 years and 2632 had infarction with 14% (1605) meeting all three National Institute of Neurological Disorders and Stroke study criteria and so being potentially eligible for thrombolysis. If the time window is increased to 4.5 h then only another 2% became eligible. If the age limit was removed for treatment, the percentage potentially appropriate for tissue plasminogen activator increased to 23% within 3 h and 26% within 4.5 h. Overall, 1.4% (160) of patients were thrombolysed. INTERPRETATION: Thrombolysis rates are currently low in the UK. 14% of patients in this sample were potentially suitable for thrombolysis using the 3 h time window. This would only increase marginally if thrombolysis was extended to include those up to 4.5 h. The greatest impact on increasing the proportion of patients suitable for thrombolysis would be to increase the number of patients presenting early and by demonstrating that the treatment is safe and effective in patients over 80 years of age. PMID- 20581131 TI - Small RNA-based silencing strategies for transposons in the process of invading Drosophila species. AB - Colonization of a host by an active transposon can increase mutation rates or cause sterility, a phenotype termed hybrid dysgenesis. As an example, intercrosses of certain Drosophila virilis strains can produce dysgenic progeny. The Penelope element is present only in a subset of laboratory strains and has been implicated as a causative agent of the dysgenic phenotype. We have also introduced Penelope into Drosophila melanogaster, which are otherwise naive to the element. We have taken advantage of these natural and experimentally induced colonization processes to probe the evolution of small RNA pathways in response to transposon challenge. In both species, Penelope was predominantly targeted by endo-small-interfering RNAs (siRNAs) rather than by piwi-interacting RNAs (piRNAs). Although we do observe correlations between Penelope transcription and dysgenesis, we could not correlate differences in maternally deposited Penelope piRNAs with the sterility of progeny. Instead, we found that strains that produced dysgenic progeny differed in their production of piRNAs from clusters in subtelomeric regions, possibly indicating that changes in the overall piRNA repertoire underlie dysgenesis. Considered together, our data reveal unexpected plasticity in small RNA pathways in germ cells, both in the character of their responses to invading transposons and in the piRNA clusters that define their ability to respond to mobile elements. PMID- 20581133 TI - Sugar refining reveals a further specificity for autoantibodies in multifocal motor neuropathy. PMID- 20581134 TI - A case for more case studies: reading epilepsy from the dominant temporo occipital region. PMID- 20581135 TI - The 'eyes' have it: a window into non-length-dependent small fibre neuropathy with corneal confocal microscopy. PMID- 20581136 TI - Does the primary literature provide support for clinical signs used to distinguish psychogenic nonepileptic seizures from epileptic seizures? AB - Psychogenic non-epileptic seizures (PNES) represent a diagnostic challenge. When trying to distinguish between PNES and epileptic seizures (ES), clinicians rely on the presence or absence of several clinical signs. The purpose of this review is to establish the extent to which these signs are supported by primary data from the literature. A Medline search was used to identify primary studies that used video-EEG to define the presence or absence of different clinical signs in PNES and ES. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. 34 studies matched the inclusion criteria. A specific sign was considered well supported by the data from the primary literature if we were able to identify at least two controlled studies demonstrating its usefulness and if the data from other studies were supportive. There is good evidence from the literature that long duration, occurrence from apparent sleep with EEG-verified wakefulness, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, closed eyes during the episode, ictal crying, memory recall and absence of postictal confusion are signs that distinguish PNES from ES. Postictal stertorous breathing proved to distinguish convulsive PNES from generalised tonic clonic seizures (GTCS) and should be added to the list of useful clinical signs. The final clinical diagnosis should encompass all available data and should not rely on any single sign alone. PMID- 20581137 TI - Motor neuropathies and serum IgM binding to NS6S heparin disaccharide or GM1 ganglioside. AB - BACKGROUND: Serum IgM binding to GM1 ganglioside (GM1) is often associated with chronic acquired motor neuropathies. This study compared the frequency and clinical associations of serum IgM binding to a different antigen, a disulphated heparin disaccharide (NS6S), with results of IgM binding to GM1. METHODS: Serums and clinical features were retrospectively compared from 75 patients with motor neuropathies and 134 controls with amyotrophic lateral sclerosis (ALS), chronic immune demyelinating polyneuropathy (CIDP) and sensory neuropathies. Clinical correlations of positive IgM anti-GM1 testing found in 27 of 2113 unselected serums were also reviewed. Serum testing for IgM binding to NS6S and GM1 used covalent antigen linkage to ELISA plates. RESULTS: High titre IgM binding to NS6S and GM1 each occurred in 43%, and to one of the two in 64%, of motor neuropathy patients. Motor neuropathy syndromes were present in 25 of 27 patients with high titre serum IgM binding to GM1 in the unselected serums. IgM anti-GM1 or NS6S antibody related motor neuropathy syndromes usually have asymmetric, predominantly distal, upper extremity weakness. CONCLUSIONS: IgM binding to NS6S disaccharide is associated with motor neuropathy syndromes and occurs with similar frequency to IgM binding to GM1. Testing for IgM binding to NS6S in addition to GM1 increases the frequency of finding IgM autoantibodies in motor neuropathies from 43% to 64%. High titres of serum IgM binding to GM1, tested with covalent ELISA methodology, have 93% specificity for motor neuropathy syndromes. High titres of serum IgM binding to NS6S have specificity for immune motor neuropathies compared with ALS and CIDP. PMID- 20581139 TI - Segmental innervation in lumbosacral transitional vertebrae (LSTV): a comparative clinical and intraoperative EMG study. AB - BACKGROUND: Despite the high prevalence of lumbosacral transitional vertebrae (LSTV), little is known about the segmental innervation in this condition. METHODS: The authors performed a prospective comparative clinical evaluation and an intraoperative electromyographic (EMG) investigation on patients with six lumbar vertebral bodies (6LVB) and on patients with five lumbar vertebrae (5LVB). First, clinical pain distribution in 80 patients (46 patients with 6LVB, 34 patients with 5LVB) with degenerative lumbar diseases were analysed between patient groups. Intraoperative EMG monitoring of five lower-limb muscles was performed. Compound muscle action potentials were obtained from 100 nerve roots of our 80 patients. RESULTS: The EMG results compared fairly to the clinical findings: 40 CMAPs from 5LVB and 60 CMAPs from 6LVB patients were compared with each other within L3 to S levels. First, there was no difference between groups in the pattern of radicular pain and myotomal innervation at the level L3/4 and L4/5 (p=0.39-1.0). Second, the nerve root stimulated at the L5/6 level compares to the S1 root in 5LVB patients; the only difference was found in a coinnervation of the biceps femoris muscle that is less frequent in 6LVB patients (p=0.02). Third, the nerve root at the L6/S level corresponds to the S1 as well as to the S2 root in 5LVB patients. CONCLUSION: Intraoperative EMG monitoring of surgically decompressed nerve roots was found to be the ideal means of unequivocal determination of segmental innervation in LSTV patients. PMID- 20581138 TI - Non-length-dependent small fibre neuropathy. Confocal microscopy study of the corneal innervation. AB - BACKGROUND: It has been recently observed that small fibre neuropathy (SFN) may present as distal symmetrical polyneuropathy and with atypical non-length dependent pattern. OBJECTIVE: To describe a small series of patients with non length-dependent SFN, investigating corneal innervation with corneal confocal microscopy (CCM). METHODS: Evaluation of the corneal nerve fibre density using CCM in six women with non-length-dependent SFN. The patients were characterised by sensory disturbance involving proximal regions of the limbs, face and trunks, and the diagnosis was confirmed by the findings of decreased intraepidermal nerve fibre density on skin biopsy. RESULTS: Six women, aged 35-64, had non-length dependent SFN, related to Crohn disease, impaired glucose tolerance and Sjogren's syndrome, or idiopathic (three cases). In all patients, CCM demonstrated decreased corneal nerve fibre density (12.5-23.4/mm(2); normal, >30.6/mm(2)). CONCLUSION: Non-length-dependent SFN may represent an intriguing diagnostic problem because of its puzzling presentation and the need for special investigations for its confirmation. In this perspective, CCM may provide a useful, non-invasive tool to complement the diagnostic workup. PMID- 20581140 TI - Neurological picture. MRI of metronidazole induced cerebellar ataxia. PMID- 20581141 TI - Patterns of non-traumatic myelopathies in Yaounde (Cameroon): a hospital based study. AB - BACKGROUND: The relative frequency of compressive and non-compressive myelopathies and their aetiologies have not been evaluated extensively in most sub-Saharan African countries. The case of Cameroon is studied. METHODS: Admission registers and case records of patients in the neurology and neurosurgery departments of the study hospital were reviewed from January 1999 to December 2006. RESULTS: 224 (9.7% of all admissions) cases were non-traumatic paraplegia/paraparesis or tetraplegia/tetraparesis and 147 were due to myelopathies, representing 6.3% of all cases admitted during the study period and 65.6% of cases of paraplegia or tetraplegia; 88% were compressive myelopathies. Aetiologies were dominated by primary and secondary spinal tumours (mainly prostate carcinoma, lymphoma and liver carcinoma) that each accounted for 24.5% of cases. Other causes included spinal tuberculosis (12.9%), tropical spastic paraparesis (five positive for human T cell lymphotrophic virus (HTLV)-I and one for HTLV-II) (4.8%), spinal degenerative disease (4.1%), acute transverse myelitis (4.1%), HIV myelopathy (1.4%), vitamin B12 deficiency myelopathy and multiple sclerosis (0.7%). No aetiology was found in 21.1% of participants. CONCLUSIONS: Myelopathies in our setting are dominated by spinal compressions. Metastasis is a leading cause of spinal cord compression with liver carcinoma being more frequent than reported elsewhere. Infections nevertheless remain a major cause of spinal cord disease and both cancers and infections constitute public health targets for reducing the incidence of myelopathies. PMID- 20581142 TI - Neurological picture. Anterior spinal artery aneurysm presenting with spinal cord compression: MRI and MRI angiographic findings. PMID- 20581143 TI - Incidence of subarachnoid haemorrhage in the Aconcagua Valley, Chile: a community based, prospective surveillance project. AB - BACKGROUND: An epidemiological surveillance project was set up in Central Chile to detect cases of subarachnoid haemorrhage (SAH) and its incidence. METHODS: Community-based prospective surveillance project carried out between 1 July 2000 and 30 June 2003, in the Aconcagua Valley in Central Chile. The authors ascertained all possible cases using multiple overlapping sources. Incidence rates were age-sex-adjusted. RESULTS: The authors identified 33 first-ever cases; 19 were women. The mean age (SD, range) was 50.7 (17.9, 16 to 82). The incidence per 100,000 age-sex adjusted to the world population was 5.1 (4.4 men, 5.6 women). The 30-day case-death rate was 54.5% (95% CI 38.0 to 70.2), and the prehospital death rate 21.2% (95% CI 10.7 to 37.7). CONCLUSIONS: The incidence rate in Aconcagua is notably similar to that reported previously in Northern Chile and lower than in many high-income western populations. The lower incidence rates found in these two Chilean populations might be due to their younger age. A trend towards a higher 30-day case-death rate found in Central Chile is possibly associated with its higher rurality and therefore lesser accessibility to preventive measures and medical care. PMID- 20581144 TI - Refractory central supratentorial hiccup partially relieved with vagus nerve stimulation. PMID- 20581145 TI - Isolated ischaemic lesions in the foot motor area mimic peripheral lower-limb palsy. PMID- 20581146 TI - IL-12p35 promotes antibody-induced joint inflammation by activating NKT cells and suppressing TGF-beta. AB - The functional role of IL-12 in rheumatoid arthritis is controversial. Moreover, whether IL-12 contributes to regulation of Ab-induced joint inflammation remains unclear. To address these issues, we explored the functional roles of IL-12 in Ab induced arthritis using the K/BxN serum transfer model. IL-12p35(-/-) and IL 12Rbeta(2)(-/-) mice were resistant to the development of arthritis. Injection of K/BxN serum into IL-12p40-yellow fluorescence protein reporter (yet40) mice induced CD11b(+) cells, CD11c(+) cells, and Gr-1(+) granulocytes to produce IL 12p40 in the joints. The levels of IFN-gamma, IL-4, and IL-6 production were lower in joint tissues of IL-12p35(-/-) and IL-12Rbeta(2)(-/-) mice than in B6 mice, whereas levels of TGF-beta expression were higher. Administering IL-12p35( /-) mice rIL-12 or IFN-gamma restored joint inflammation and suppressed TGF-beta production in joint tissues. Moreover, administering neutralizing anti-TGF-beta mAb enhanced joint inflammation. Among the immune cells that infiltrated joint tissues during Ab-induced arthritis, NKT cells expressed IL-12beta(2) receptors. Furthermore, the adoptive transfer of splenocytes from B6 or Gr-1(+) granulocyte depleted mice restored joint inflammation in IL-12Rbeta(2)(-/-) mice as much as in B6 mice, whereas splenocytes from Jalpha18(-/-) mice did not. These findings indicate that signals via IL-12beta(2) receptors on NKT cells play a critical role in the development of Ab-induced arthritis. The IL-12p35/IFN-gamma axis promotes Ab-induced joint inflammation by activating NKT cells and suppressing TGF-beta, which may provide novel information for the development of new therapeutic strategies for the inhibition of rheumatoid arthritis. PMID- 20581148 TI - Multifront assault on antigen presentation by Japanese encephalitis virus subverts CD8+ T cell responses. AB - Japanese encephalitis virus (JEV) is a frequent cause of acute and epidemic viral encephalitis. However, there is little information describing the mechanisms by which JEV subverts immune responses that may predispose the host to secondary infections. In this study, we found that JEV induced the subversion of CD8(+) T cell responses in a transient manner that was closely correlated with viral multiplication. Subsequently, analysis using a TCR-transgenic system revealed that CD8(+) T cells purified from JEV-infected mice showed impaired responses, and that naive CD8(+) T cells adoptively transferred into JEV-infected recipients showed less expanded responses. Furthermore, JEV altered the splenic dendritic cell (DC) subpopulation via preferential depletion of CD8alpha(+)CD11c(+) DCs without changing the plasmacytoid DCs and induced a significant reduction in the surface expression of MHC class II and CD40, but not MHC class I, CD80, and CD86 molecules. Finally, JEV was shown to inhibit the presentation of MHC class I restricted Ag in DCs, and this immune suppression was ameliorated via the activation of DCs by TLR agonists. Collectively, our data indicate that JEV precludes the functions of Ag-presenting machinery, such as depletion of CD8alpha(+)CD11c(+) DCs and downregulation of MHC class I-restricted Ag presentation, thereby leading to immune subversion of CD8(+) T cells. PMID- 20581147 TI - Dendritic cell-mediated in vivo bone resorption. AB - Osteoclasts are resident cells of the bone that are primarily involved in the physiological and pathological remodeling of this tissue. Mature osteoclasts are multinucleated giant cells that are generated from the fusion of circulating precursors originating from the monocyte/macrophage lineage. During inflammatory bone conditions in vivo, de novo osteoclastogenesis is observed but it is currently unknown whether, besides increased osteoclast differentiation from undifferentiated precursors, other cell types can generate a multinucleated giant cell phenotype with bone resorbing activity. In this study, an animal model of calvaria-induced aseptic osteolysis was used to analyze possible bone resorption capabilities of dendritic cells (DCs). We determined by FACS analysis and confocal microscopy that injected GFP-labeled immature DCs were readily recruited to the site of osteolysis. Upon recruitment, the cathepsin K-positive DCs were observed in bone-resorbing pits. Additionally, chromosomal painting identified nuclei from female DCs, previously injected into a male recipient, among the nuclei of giant cells at sites of osteolysis. Finally, osteolysis was also observed upon recruitment of CD11c-GFP conventional DCs in Csf1r(-/-) mice, which exhibit a severe depletion of resident osteoclasts and tissue macrophages. Altogether, our analysis indicates that DCs may have an important role in bone resorption associated with various inflammatory diseases. PMID- 20581149 TI - Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. AB - Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN-gamma(+), granzyme B(+) cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vbeta repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities. PMID- 20581151 TI - Tumor-activated monocytes promote expansion of IL-17-producing CD8+ T cells in hepatocellular carcinoma patients. AB - The proinflammatory IL-17-producing CD8(+) T cells (Tc17 cells) have recently been detected in tumors, but the nature and regulation of these cells in human tumors are presently unknown. We have recently found that IL-17(+) cells are accumulated in human hepatocellular carcinomas (HCC), where they promote disease progression by fostering angiogenesis. In this study, we showed that Tc17 cells constitute a remarkable portion of IL-17-producing cells in human HCC. Although most circulating Tc17 cells were negative for IFN-gamma, >80% of Tc17 cells in HCC tissues were positive for IFN-gamma, and they were enriched predominantly in invading tumor edge. Most CD68(+) cells located in invading tumor edge exhibited an activated phenotype and, accordingly, the activated monocytes isolated from HCC tissues were significantly superior to those isolated from nontumor tissues in inducing expansion of Tc17 cells in vitro with phenotypic features similar to those isolated from tumors. Compared with IL-17(-)IFN-gamma(+)CD8(+) cells, these IFN-gamma(+)Tc17 cells have significantly higher expression of proinflammatory cytokines (IL-2, IL-22, and TNF-alpha), but reduced expression of granzyme B and perforin. Moreover, we found that tumor-activated monocytes secreted a set of key cytokines (IL-1beta, IL-6, and IL-23) to trigger the proliferation of Tc17 cells. These data reveal an intriguing mechanism in which human Tc17 cells are generated by a fine-tuned collaborative action between different types of immune cells in distinct tumor microenvironments. PMID- 20581150 TI - Phosphorylation of leukocyte PECAM and its association with detergent-resistant membranes regulate transendothelial migration. AB - Leukocyte migration across the endothelial lining is a critical step in the body's response to infection and inflammation. The homophilic interaction between endothelial PECAM and leukocyte PECAM is essential for this process. The molecular events that are triggered in the endothelial cell by PECAM engagement have been well characterized; however, the function of leukocyte PECAM remains to be elucidated. To study this, we first blocked leukocyte transmigration using anti-PECAM Ab and then specifically activated leukocyte PECAM. This was sufficient to overcome the block and promote transmigration, suggesting an active signaling role for leukocyte PECAM. Consistent with this, we found that ligation of leukocyte PECAM induces phosphorylation of two tyrosine residues on its cytoplasmic tail. By performing RNA interference-rescue experiments, we demonstrate that these phosphorylation events are indispensable for transendothelial migration. Finally, we show that leukocyte PECAM translocates to a detergent-resistant membrane (DRM) during transmigration. PECAM localized in DRMs displays reduced phosphorylation and does not support transmigration. Together, these data support a model whereby engagement of leukocyte PECAM induces its transient tyrosine phosphorylation and induction of downstream signals that drive transmigration. These signals are then downregulated following PECAM translocation to DRMs. PMID- 20581152 TI - A genome-wide profiling of the humoral immune response to Chlamydia trachomatis infection reveals vaccine candidate antigens expressed in humans. AB - A whole genome scale proteome array consisting of 908 open reading frames encoded in Chlamydia trachomatis genome and plasmid was used to profile anti-chlamydial Ab responses. A total of 719 chlamydial proteins was recognized by one or more antisera from 99 women urogenitally infected with C. trachomatis. Revealing such a large C. trachomatis ANTIGENome in humans might partially be attributed to the significantly improved detection sensitivity of the whole genome scale proteome array assay because both linear and conformation-dependent Abs were detected by the array assay. Twenty-seven of the 719 Ags were recognized by >or=50% antisera, thus designated as immunodominant Ags. Comparison of Ag profiles recognized by live chlamydial organism-infected versus dead organism-immunized hosts led to the identification of infection-dependent or in vivo expressed Ags. The infection dependent Ags induced Abs only in live organism-infected, but not in dead organism-immunized hosts. Many of these Ags were highly expressed during replication, but only minimally packaged into the infectious elementary bodies. Because inactivated whole chlamydial organism-based vaccines failed to induce protection in humans, identification of the infection-dependent or in vivo expressed immunodominant Ags in humans should greatly facilitate the selection of promising chlamydial subunit vaccine candidates for further evaluation. This approach may also be applicable to other pathogens. PMID- 20581153 TI - Dyslipidemia induces opposing effects on intrapulmonary and extrapulmonary host defense through divergent TLR response phenotypes. AB - Dyslipidemia influences innate immune responses in the bloodstream, but whether and how pulmonary innate immunity is sensitive to circulating lipoproteins is largely unknown. To define whether dyslipidemia impacts responses to bacteria in the airspace and, if so, whether differently from its effects in other tissues, airspace, bloodstream, and i.p. responses to LPS and Klebsiella pneumoniae were investigated using murine models of dyslipidemia. Dyslipidemia reduced neutrophil (PMN) recruitment to the airspace in response to LPS and K. pneumoniae by impairing both chemokine induction in the airspace and PMN chemotaxis, thereby compromising pulmonary bacterial clearance. Paradoxically, bacteria were cleared more effectively from the bloodstream during dyslipidemia. This enhanced systemic response was due, at least in part, to basal circulating neutrophilia and basal TLR4/MyD88-dependent serum cytokine induction and enhanced serum cytokine responses to systemically administered TLR ligands. Dyslipidemia did not globally impair PMN transvascular trafficking to, and host defense within all loci, because neutrophilia, cytokine induction, and bacterial clearance were enhanced within the infected peritoneum. Peritoneal macrophages from dyslipidemic animals were primed for more robust TLR responses, reflecting increased lipid rafts and increased TLR4 expression, whereas macrophages from the airspace, in which cholesterol was maintained constant during dyslipidemia, had normal responses and rafts. Dyslipidemia thus imparts opposing effects upon intra- and extrapulmonary host defense by inducing tissue-divergent TLR response phenotypes and dysregulating airspace/blood compartmental levels of PMNs and cytokines. We propose that the airspace is a "privileged" site, thereby uniquely sensitive to dyslipidemia. PMID- 20581155 TI - Plasma B-type natriuretic peptide as a predictor of mortality in community dwelling older adults with Chagas disease: 10-year follow-up of the Bambui Cohort Study of Aging. AB - In this study, the authors aimed to investigate the prognostic value of brain type natriuretic peptide (BNP) for all-cause mortality among persons with Chagas disease, a parasitic disease caused by the protozoan Trypanosoma cruzi. The authors used data on 1,398 participants (37.5% infected with T. cruzi) aged 60 years and over from the Bambui Cohort Study of Aging in Brazil. From 1997 to 2007, 512 participants died, leading to 12,406 person-years of observation. The hazard ratio for death was 1.27 for each unit of log-transformed BNP level (95% confidence interval (CI: 1.11, 1.45) among infected persons, independent of potentially confounding factors. Infected persons with baseline BNP levels in the top quartile had a risk of death twice that of persons in the bottom quartile (hazard ratio = 2.07, 95% CI: 1.29, 3.32). The discriminatory ability of BNP in predicting mortality (C = 0.69, 95% CI: 0.66, 0.71) was similar to that of an electrocardiogram (C = 0.68, 95% CI: 0.65, 0.71), with reasonably stable risk discrimination over time. BNP is a strong predictor of mortality in older adults with Chagas disease. Although the usefulness of BNP for risk stratification in this parasitic disease remains a topic of debate, this study found that BNP-based risk discrimination is at least comparable to that of an electrocardiogram. PMID- 20581160 TI - Case report: intraoperative management of extreme hemodilution in a patient with a severed axillary artery. AB - We present a case of extreme hemodilution in which appropriately crossmatched blood was not available. A 53-year-old man was admitted to our hospital because of hemorrhagic shock due to multiple stab wounds. His blood type was B, Rh negative, and his intravascular fluid volume was maintained with balanced salt solution and plasma substitutes, i.e., hydroxyethyl starch. His hemoglobin reached a nadir of 0.7 g/dL and hematocrit 2.2% before being transfused. No evidence of cardiac ischemia was noted and he was discharged in good condition. Extreme hemodilution can be successfully managed by maintaining a normal blood volume, 100% oxygen, and the use of plasma substitutes. PMID- 20581161 TI - Technical communication: robot-assisted regional anesthesia: a simulated demonstration. AB - Recent advances in robotically assisted telesurgery offer expert surgical care for the geographically remote patient. Similar advances in teleanesthesia will be necessary to bring comparable perioperative care to the geographically remote patient. Although many preliminary investigations into teleanesthesia are underway, none involve remote performance of anesthesia-related procedures. Herein, we describe the placement of ultrasound-guided nerve blocks into an ultrasound phantom using the da Vinci multipurpose surgical robotic system (Intuitive Surgical, Sunnyvale, CA). Both single-injection and perineural catheter techniques were successfully performed by an operator who was not physically present at the bedside. PMID- 20581163 TI - The limited value of sequencing cases based on their probability of cancellation. AB - BACKGROUND: Case cancellations on the day of surgery reduce operating room (OR) and anesthesia group productivity. One strategy to reduce the impact of case cancellations on productivity is to assign high-risk cases to start last in the OR workday. To evaluate the utility of this intervention, we used a database of canceled cases to model the process of identifying high-risk cases and resequencing them to be the surgeons' last cases of the day. METHODS: Descriptive information was prospectively collected on 1 year of canceled cases. A comparison group of completed cases served as controls. Predictors of case cancellation were identified and used to calculate the number of cases that would require resequencing for 1 cancellation to occur at the end of the day. The proportion of total OR hours relevant to each predictor was assessed. To assess the desirability of this strategy, surgeons were surveyed regarding their scheduling preferences for patients at high risk for cancellation. RESULTS: During the study period, 946 of 12,253 cases were canceled. Strong predictors of cancellation included percentage of missed clinic appointments (number of cases requiring resequencing = 5.27) and insurance status (number of cases requiring resequencing = 8.87 for Medicaid). The predictor accounting for the most scheduled time was residence in Chicago (5.1% of total hours). No predictor both required the resequencing of 5 or fewer cases to prevent 1 cancellation in the middle of the day and accounted for >4% of scheduled time. Survey results demonstrated that in addition to cancellation probability, factors such as case complexity also influenced surgeons' sequencing preferences. CONCLUSION: Highly sensitive predictors of case cancellation are impractical for sequencing purposes because they account for too few hours of scheduled OR time. Effort invested in identifying and resequencing cases at high risk for cancellation likely has limited value. PMID- 20581162 TI - The effectiveness of benzydamine hydrochloride spraying on the endotracheal tube cuff or oral mucosa for postoperative sore throat. AB - BACKGROUND: The etiology of postoperative sore throat (POST) is considered to be the result of laryngoscopy, intubation damage, or inflated cuff compression of the tracheal mucosa. In this study, we compared the effectiveness in alleviating POST using different approaches to benzydamine hydrochloride (BH) administration by spraying the endotracheal tube (ET) cuff or the oropharyngeal cavity, or both. METHODS: Three hundred eighty patients were included in this prospective and double-blind study, which was randomized into 4 groups: group A, oropharyngeal cavity spray of BH, and distilled water on the ET cuff; group B, both the oropharyngeal cavity and the ET cuff received BH spray; group C, the ET cuff received BH spray, and the oropharyngeal cavity received distilled water; and group D, distilled water sprayed on both the ET tube and into the oropharyngeal cavity. The patients were examined for sore throat (none, mild, moderate, severe) at 0, 2, 4, and 24 hours postextubation. RESULTS: The incidence of POST was 23.2%, 13.8%, 14.7%, and 40.4% in groups A, B, C, and D, respectively. POST occurred significantly less frequently in groups B and C compared with group D (odds ratio: 0.36; 95% confidence interval: 0.21-0.60; P < 0.05). However, there was no significant difference between groups A and D (odds ratio: 0.62; 95% confidence interval: 0.38-1.01). Moreover, there was no significant interaction between spraying BH over the oropharyngeal cavity and the ET cuff on the incidence of POST (P = 0.088). The severity of POST was significantly more intense in group D compared with groups B and C (P < 0.001). Group B had a significantly higher incidence of local numbness, burning, and/or stinging sensation compared with patients in group D (P < 0.05). CONCLUSIONS: This study indicates that spraying BH on the ET cuff decreases the incidence and severity of POST without increased BH-related adverse effects. PMID- 20581164 TI - Computational modeling and prototyping of a pediatric airway management instrument. AB - BACKGROUND: Anterior retraction of the tongue is used to enhance upper airway patency during pediatric fiberoptic intubation. This can be achieved by the use of Magill forceps as a tongue retractor, but lingual grip can become unsteady and traumatic. Our objective was to modify this instrument using computer-aided engineering for the purpose of stable tongue retraction. METHODS: We analyzed the geometry and mechanical properties of standard Magill forceps with a combination of analytical and empirical methods. This design was captured using computer aided design techniques to obtain a 3-dimensional model allowing further geometric refinements and mathematical testing for rapid prototyping. RESULTS: On the basis of our experimental findings we adjusted the design constraints to optimize the device for tongue retraction. Stereolithography prototyping was used to create a partially functional plastic model to further assess the functional and ergonomic effectiveness of the design changes. To reduce pressure on the tongue by regular Magill forceps, we incorporated (1) a larger diameter tip for better lingual tissue pressure profile, (2) a ratchet to stabilize such pressure, and (3) a soft molded tip with roughened surface to improve grip. CONCLUSION: Computer-aided engineering can be used to redesign and prototype a popular instrument used in airway management. On a computational model, our modified Magill forceps demonstrated stable retraction forces, while maintaining the original geometry and versatility. Its application in humans and utility during pediatric fiberoptic intubation are yet to be studied. PMID- 20581165 TI - At-a-glance monitoring: covert observations of anesthesiologists in the operating room. AB - BACKGROUND: Patient monitoring displays are designed to improve patient safety, and yet little is known about how anesthesiologists interact with these displays. Previous studies of clinician behavior used an observer in the operating room, which may have altered behavior. We describe a covert observation technique to determine how often and for how long anesthesiologists actually look at the monitoring display during different segments of the maintenance phase of anesthesia, and to determine whether this changed with more than 1 anesthesia provider or during concomitant activities such as reading. METHODS: Five staff anesthesiologists, 2 anesthesia fellows, 3 anesthesia residents, and 2 medical students were covertly videotaped across 10 dual anesthesia provider cases and 10 solo cases. Videotapes were later segmented (5 minutes postinduction [early maintenance], mid-maintenance, and immediately before the drapes came down [late maintenance]) and coded for looking behavior at the patient monitor, anesthesia chart, and other reading material. RESULTS: Anesthesiologists looked at the monitor in 1- to 2-second glances, performed frequently throughout the 3 segments of maintenance anesthesia. Overall, the patient monitor was looked at only 5 of the analyzed time, which is less than has previously been reported. Monitoring behavior was constant across the segments of maintenance anesthesia and was not significantly affected by the number of anesthesia providers or role (trainee vs. senior). In contrast, charting behavior and other reading material viewing changed significantly over the analyzed segments of maintenance anesthesia. CONCLUSIONS: The presence of "at-a-glance monitoring" has implications for the design of patient monitoring displays. Displays should be developed to optimize the information obtained from brief glances at the monitor. PMID- 20581166 TI - Location and duration of treatment of cystic fibrosis respiratory exacerbations do not affect outcomes. AB - RATIONALE: Individuals with cystic fibrosis (CF) are subject to recurrent respiratory infections (exacerbations) that often require intravenous antibiotic treatment and may result in permanent loss of lung function. The optimal means of delivering therapy remains unclear. OBJECTIVES: To determine whether duration or venue of intravenous antibiotic administration affect lung function. METHODS: Data were retrospectively collected on 1,535 subjects recruited by the US CF Twin and Sibling Study from US CF care centers between 2000 and 2007. MEASUREMENTS AND MAIN RESULTS: Long-term decline in FEV1 after exacerbation was observed regardless of whether antibiotics were administered in the hospital (mean, -3.3 percentage points [95% confidence interval, -3.9 to -2.6]; n = 602 courses of therapy) or at home (mean, -3.5 percentage points [95% confidence interval, -4.5 to -2.5]; n = 232 courses of therapy); this decline was not different by venue using t tests (P = 0.69) or regression (P = 0.91). No difference in intervals between courses of antibiotics was observed between hospital (median, 119 d [interquartile range, 166]; n = 602) and home (median, 98 d [interquartile range, 155]; n = 232) (P = 0.29). Patients with greater drops in FEV1 with exacerbations had worse long-term decline even if lung function initially recovered with treatment (P < 0.001). Examination of FEV1 measures obtained during treatment for exacerbations indicated that improvement in FEV1 plateaus after 7-10 days of therapy. CONCLUSIONS: Intravenous antibiotic therapy for CF respiratory exacerbations administered in the hospital and in the home was found to be equivalent in terms of long-term FEV1 change and interval between courses of antibiotics. Optimal duration of therapy (7-10 d) may be shorter than current practice. Large prospective studies are needed to answer these essential questions for CF respiratory management. PMID- 20581167 TI - Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. AB - RATIONALE: Respiratory events are common in hematology and oncology patients and manifest as hypoxemic acute respiratory failure (ARF) in up to half the cases. Identifying the cause of ARF is crucial. Fiberoptic bronchoscopy with bronchoalveolar lavage (FO-BAL) is an invasive test that may cause respiratory deterioration. Recent noninvasive diagnostic tests may have modified the risk/benefit ratio of FO-BAL. OBJECTIVES: To determine whether FO-BAL in cancer patients with ARF increased the need for intubation and whether noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL. METHODS: We performed a multicenter randomized controlled trial with sample size calculations for both end points. Patients with cancer and ARF of unknown cause who were not receiving ventilatory support at intensive care unit admission were randomized to early FO-BAL plus noninvasive tests (n = 113) or noninvasive tests only (n = 106). The primary end point was the number of patients needing intubation and mechanical ventilation. The major secondary end point was the number of patients with no identified cause of ARF. MEASUREMENTS AND MAIN RESULTS: The need for mechanical ventilation was not significantly greater in the FO-BAL group than in the noninvasive group (35.4 vs. 38.7%; P = 0.62). The proportion of patients with no diagnosis was not smaller in the noninvasive group (21.7 vs. 20.4%; difference, -1.3% [-10.4 to 7.7]). CONCLUSIONS: FO-BAL performed in the intensive care unit did not significantly increase intubation requirements in critically ill cancer patients with ARF. Noninvasive testing alone was not inferior to noninvasive testing plus FO-BAL for identifying the cause of ARF. Clinical trial registered with www.clinicaltrials.gov (NCT00248443). PMID- 20581168 TI - Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension. AB - RATIONALE: Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasineoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. OBJECTIVES: To assess whether there is larger-scale genomic instability. METHODS: We performed genome wide microarray copy number analysis on pulmonary artery endothelial cells and smooth muscle cells isolated from the lungs of patients with PAH. MEASUREMENTS AND MAIN RESULTS: Mosaic chromosomal abnormalities were detected in PAEC cultures from five of nine PAH lungs but not in normal (n = 8) or disease control subjects (n = 5). Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female subjects with mosaic loss of the X chromosome, methylation analysis showed that the active X was deleted. One subject also showed completely skewed X-inactivation in the nondeleted cells, suggesting the pulmonary artery endothelial cell population was clonal before the acquisition of the chromosome abnormality. CONCLUSIONS: Our data indicate a high frequency of genetically abnormal subclones within PAH lung vessels and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH. PMID- 20581169 TI - Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. AB - RATIONALE: Pulmonary arterial hypertension (PAH) is a progressive condition with a poor prognosis. Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in its pathobiology. OBJECTIVES: To assess safety, tolerability, and efficacy of the PDGFR inhibitor imatinib in patients with PAH. METHODS: Patients with PAH in functional classes II-IV were enrolled in a 24-week randomized, double-blind, placebo-controlled pilot study. Patients received imatinib (an inhibitor of PDGFR activity) 200 mg orally once daily (or placebo), which was increased to 400 mg if the initial dose was well tolerated. The primary endpoints were safety and change from baseline in the 6-minute-walk distance (6MWD). Secondary endpoints included hemodynamics and functional classification. MEASUREMENTS AND MAIN RESULTS: Fifty-nine patients enrolled (imatinib [n = 28]; placebo [n = 31]); 42 completed the study. Dropouts were equally matched between the two groups. In the intention-to-treat (ITT) population there was no significant change in the 6MWD (mean +/- SD) in the imatinib versus placebo group (+22 +/- 63 versus -1.0 +/- 53 m). There was a significant decrease in pulmonary vascular resistance (imatinib -300 +/- 347 versus placebo -78 +/- 269 dynes . s . cm-5, P < 0.01) and increase in cardiac output (imatinib +0.6 +/- 1.2 versus placebo -0.1 +/- 0.9 L/min, P = 0.02). Serious adverse events occurred in 11 imatinib recipients (39%) and 7 placebo recipients (23%). Three deaths occurred in each group. Post hoc subgroup analyses suggest that patients with greater hemodynamic impairment may respond better than patients with less impairment. CONCLUSIONS: These data from a Phase II study are consistent with imatinib being well tolerated in patients with PAH, and provide proof of concept for further studies evaluating its safety, tolerability, and efficacy in PAH. Clinical trial registered with www.clinicaltrials.gov (NCT00477269). PMID- 20581170 TI - Macrophage migration inhibitory factor promotes tumor growth in the context of lung injury and repair. AB - RATIONALE: Tissue injury and repair involve highly conserved processes governed by mechanisms that can be co-opted in tumors. We hypothesized that soluble factors released during the repair response to lung injury would promote orthotopic tumor growth. OBJECTIVES: To determine whether lung injury promoted growth of orthotopic lung tumors and to study the molecular mechanisms. METHODS: We initiated lung injury in C57Bl6 mice using different stimuli, then injected Lewis lung carcinoma cells during the repair phase. We assessed tumor growth 14 days later. We measured tumor angiogenesis, cytokine expression, proliferation, and apoptosis. MEASUREMENTS AND MAIN RESULTS: Regardless of the mechanism, injured lungs contained more numerous and larger tumors than sham-injured lungs. Tumors from injured lungs were no more vascular, but had higher levels of proliferation and reduced rates of apoptosis. The cytokine macrophage migration inhibitory factor (MIF) was highly expressed in both models of tissue injury. We observed no increase in tumor growth after lung injury in MIF knockout mice. We induced lung-specific overexpression of MIF in a double-transgenic mouse, and observed that MIF overexpression by itself was sufficient to accelerate the growth of orthotopic Lewis lung carcinoma tumors. CONCLUSIONS: Lung injury leads to increased expression of the cytokine MIF, which results in protection from apoptosis and increased proliferation in orthotopic tumors injected after the acute phase of injury. PMID- 20581172 TI - A novel insight into adaptive immunity in chronic obstructive pulmonary disease: B cell activating factor belonging to the tumor necrosis factor family. AB - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a disorder characterized by an abnormal inflammatory response that persists even after smoking cessation, yet the underlying mechanisms are not fully understood. OBJECTIVES: To investigate the expression of B-cell activating factor of tumor necrosis factor family (BAFF), a crucial mediator in the crosstalk between innate and adaptive immune responses, in patients with COPD and to explore its correlation with disease severity. METHODS: Using immunohistochemistry, expression of BAFF was examined in lung specimens from 21 smokers with COPD (FEV(1) = 57 +/- 5% predicted), 14 control smokers (FEV(1) = 99 +/- 2% predicted) and 8 nonsmokers (FEV(1) = 104 +/- 4% predicted). BAFF was quantified in alveolar macrophages and alveolar walls, in bronchiolar and parenchymal lymphoid follicles, and in peripheral airways and pulmonary arterioles. MEASUREMENTS AND MAIN RESULTS: In alveolar macrophages and parenchymal lymphoid follicles, BAFF expression was increased in smokers with COPD compared with control smokers and nonsmokers (P < 0.05 for all comparisons). In both compartments, BAFF was also up regulated in control smokers as compared with nonsmokers (P = 0.03 and P = 0.01). Moreover, BAFF was overexpressed in bronchiolar lymphoid follicles, alveolar walls, peripheral airways, and pulmonary arterioles from smokers with COPD compared with nonsmokers (P < 0.05 for all). Among patients with COPD, BAFF(+) macrophages were inversely related to FEV(1) (P = 0.03, Spearman's rho [r(S)] = 0.48), FEV(1)/FVC (P = 0.02, r(S) = -0.50), and Pa(O(2)) values (P = 0.01, r(S) = -0.55). CONCLUSIONS: This study demonstrated overexpression of BAFF in peripheral lung of patients with COPD, mainly in alveolar macrophages and lymphoid follicles. Moreover, BAFF expression was correlated to the degree of lung function impairment and hypoxia, suggesting that it may have a possible impact on disease severity. PMID- 20581171 TI - The angiotensin-converting enzyme 2/angiogenesis-(1-7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. AB - RATIONALE: An activated vasoconstrictive, proliferative, and fibrotic axis of the renin angiotensin system (angiotensin-converting enzyme [ACE]/angiotensin [Ang]II/AngII type 1 receptor) has been implicated in the pathophysiology of pulmonary fibrosis (PF) and pulmonary hypertension (PH). The recent discovery of a counterregulatory axis of the renin angiotensin system composed of ACE2/Ang-(1 7)/Mas has led us to examine the role of this vasoprotective axis on such disorders. OBJECTIVES: We hypothesized that Ang-(1-7) treatment would exert protective effects against PF and PH. METHODS: Lentiviral packaged Ang-(1-7) fusion gene or ACE2 cDNA was intratracheally administered into the lungs of male Sprague Dawley rats. Two weeks after gene transfer, animals received bleomycin (2.5 mg/kg). In a subsequent study, animals were administered monocrotaline (MCT, 50 mg/kg). MEASUREMENTS AND MAIN RESULTS: In the PF study, bleomycin administration resulted in a significant increase in right ventricular systolic pressure, which was associated with the development of right ventricular hypertrophy. The lungs of these animals also exhibited excessive collagen deposition, decreased expression of ACE and ACE2, increased mRNA levels for transforming growth factor beta and other proinflammatory cytokines, and increased protein levels of the AT1R. Overexpression of Ang-(1-7) significantly prevented all the above-mentioned pathophysiological conditions. Similar protective effects were also obtained with ACE2 overexpression. In the PH study, rats injected with MCT developed elevated right ventricular systolic pressure, right ventricular hypertrophy, right ventricular fibrosis, and pulmonary vascular remodeling, all of which were attenuated by Ang-(1-7) overexpression. Blockade of the Mas receptor abolished the beneficial effects of Ang-(1-7) against MCT induced PH. CONCLUSIONS: Our observations demonstrate a cardiopulmonary protective role for the ACE2/Ang-(1-7)/Mas axis in the treatment of lung disorders. PMID- 20581173 TI - Molecular and genetic analyses of the putative Proteus O antigen gene locus. AB - Proteus species are well-characterized opportunistic pathogens primarily associated with urinary tract infections (UTI) of humans. The Proteus O antigen is one of the most variable constituents of the cell surface, and O antigen heterogeneity is used for serological classification of Proteus isolates. Even though most Proteus O antigen structures have been identified, the O antigen locus has not been well characterized. In this study, we identified the putative Proteus O antigen locus and demonstrated this region's high degree of heterogeneity by comparing sequences of 40 Proteus isolates using PCR-restriction fragment length polymorphism (RFLP). This analysis identified five putative Proteus O antigen gene clusters, and the probable functions of these O antigen related genes were proposed, based on their similarity to genes in the available databases. Finally, Proteus-specific genes from these five serogroups were identified by screening 79 strains belonging to the 68 Proteus O antigen serogroups. To our knowledge, this is the first molecular characterization of the putative Proteus O antigen locus, and we describe a novel molecular classification method for the identification of different Proteus serogroups. PMID- 20581174 TI - Synthesis of trypsin-resistant variants of the Listeria-active bacteriocin salivaricin P. AB - Two-component salivaricin P-like bacteriocins have demonstrated potential as antimicrobials capable of controlling infections in the gastrointestinal tract (GIT). The anti-Listeria activity of salivaricin P is optimal when the individual peptides Sln1 and Sln2 are added in succession at a 1:1 ratio. However, as degradation by digestive proteases may compromise the functionality of these peptides within the GIT, we investigated the potential to create salivaricin variants with enhanced resistance to the intestinal protease trypsin. A total of 11 variants of the salivaricin P components, in which conservative modifications at the trypsin-specific cleavage sites were explored in order to protect the peptides from trypsin degradation while maintaining their potent antimicrobial activity, were generated. Analysis of these variants revealed that eight were resistant to trypsin digestion while retaining antimicrobial activity. Combining the complementary trypsin-resistant variants Sln1-5 and Sln2-3 resulted in a MIC(50) of 300 nM against Listeria monocytogenes, a 3.75-fold reduction in activity compared to the level for wild-type salivaricin P. This study demonstrates the potential of engineering bacteriocin variants which are resistant to specific protease action but which retain significant antimicrobial activity. PMID- 20581175 TI - Phosphoenolpyruvate carboxykinase as the sole anaplerotic enzyme in Saccharomyces cerevisiae. AB - Pyruvate carboxylase is the sole anaplerotic enzyme in glucose-grown cultures of wild-type Saccharomyces cerevisiae. Pyruvate carboxylase-negative (Pyc(-)) S. cerevisiae strains cannot grow on glucose unless media are supplemented with C(4) compounds, such as aspartic acid. In several succinate-producing prokaryotes, phosphoenolpyruvate carboxykinase (PEPCK) fulfills this anaplerotic role. However, the S. cerevisiae PEPCK encoded by PCK1 is repressed by glucose and is considered to have a purely decarboxylating and gluconeogenic function. This study investigates whether and under which conditions PEPCK can replace the anaplerotic function of pyruvate carboxylase in S. cerevisiae. Pyc(-) S. cerevisiae strains constitutively overexpressing the PEPCK either from S. cerevisiae or from Actinobacillus succinogenes did not grow on glucose as the sole carbon source. However, evolutionary engineering yielded mutants able to grow on glucose as the sole carbon source at a maximum specific growth rate of ca. 0.14 h(-1), one-half that of the (pyruvate carboxylase-positive) reference strain grown under the same conditions. Growth was dependent on high carbon dioxide concentrations, indicating that the reaction catalyzed by PEPCK operates near thermodynamic equilibrium. Analysis and reverse engineering of two independently evolved strains showed that single point mutations in pyruvate kinase, which competes with PEPCK for phosphoenolpyruvate, were sufficient to enable the use of PEPCK as the sole anaplerotic enzyme. The PEPCK reaction produces one ATP per carboxylation event, whereas the original route through pyruvate kinase and pyruvate carboxylase is ATP neutral. This increased ATP yield may prove crucial for engineering of efficient and low-cost anaerobic production of C(4) dicarboxylic acids in S. cerevisiae. PMID- 20581176 TI - Development and validation of a continuous in vitro system reproducing some biotic and abiotic factors of the veal calf intestine. AB - Following the January 2006 European ban of antibiotics used as growth promoters in the veal calf industry, new feed additives are needed in order to maintain animal health and growth performance. As an alternative to in vivo experiments in the testing of such additives, an in vitro system modeling the intestinal ecosystem of the veal calf was developed. Stabilization of the main cultured microbial groups and their metabolic activity were tracked in an in vitro continuous fermentor operated under anaerobiosis, at pH 6.5, and at a temperature of 38.5 degrees C and supplied with one of three different nutritive media (M1, M2, or M3). These media mainly differed in their concentrations of simple and complex carbohydrates and in their lipid sources. In vitro microbial levels and fermentative metabolite concentrations were compared to in vivo data, and the biochemical composition of the nutritive media was compared to that of the veal calf intestinal content. All three nutritive media were able to stabilize anaerobic and facultative anaerobic microflora, lactate-utilizing bacteria, bifidobacteria, lactobacilli, enterococci, and Bacteroides fragilis group bacteria at levels close to in vivo values. The microbiota was metabolically active, with high concentrations of lactate, ammonia, and short-chain fatty acids found in the fermentative medium. Comparison with in vivo data indicated that M3 outperformed M1 and M2 in simulating the conditions encountered in the veal calf intestine. This in vitro system would be useful in the prescreening of new feed additives by studying their effect on the intestinal microbiota levels and fermentative metabolite production. PMID- 20581177 TI - Persistence of avian influenza virus (H5N1) in feathers detached from bodies of infected domestic ducks. AB - Asian lineage highly pathogenic avian influenza virus (H5N1) continues to cause mortality in poultry and wild bird populations at a panzootic scale. However, little is known about its persistence in contaminated tissues derived from infected birds. We investigated avian influenza virus (H5N1) persistence in feathers detached from bodies of infected ducks to evaluate their potential risk for environmental contamination. Four-week-old domestic ducks were inoculated with different clades of avian influenza virus (H5N1). Feathers, drinking water, and feces were collected on day 3 postinoculation and stored at 4 degrees C or 20 degrees C. Viral persistence in samples was investigated for 360 days by virus isolation and reverse transcription-PCR. Infectious viruses persisted for the longest period in feathers, compared with drinking water and feces, at both 4 degrees C and 20 degrees C. Viral infectivity persisted in the feathers for 160 days at 4 degrees C and for 15 days at 20 degrees C. Viral titers of 10(4.3) 50% egg infectious doses/ml or greater were detected for 120 days in feathers stored at 4 degrees C. Viral RNA in feathers was more stable than the infectivity. These results indicate that feathers detached from domestic ducks infected with highly pathogenic avian influenza virus (H5N1) can be a source of environmental contamination and may function as fomites with high viral loads in the environment. PMID- 20581178 TI - Two functionally distinct ciliates dwelling in Acropora corals in the South China Sea near Sanya, Hainan Province, China. AB - We detected and characterized two distinct scuticociliate ciliates inside Acropora corals in the South China Sea. One, voraciously foraging on Symbiodinium, resembled the brown band disease of ciliates. The other, which is closely related to Paranophrys magna, grazed on detritus instead of Symbiodinium. These two ciliates may serve contrasting functions (competitor versus "cleaner") in the coral-ciliate-Symbiodinium triangular relationship. PMID- 20581179 TI - Community dynamics of bacteria in sourdough fermentations as revealed by their metatranscriptome. AB - The lactic acid bacterial (LAB) community dynamics of two wheat and two spelt sourdough fermentations that were daily back-slopped were monitored during a period of 10 days by hybridizing time-related RNA samples, representing the metatranscriptome, to an LAB functional gene microarray. To indicate the species present in each hybridized sample, annotation information for the 2,269 oligonucleotides on the microarray was used. The overall hybridization data revealed that after a transition phase of 5 days, in which atypical sourdough LAB species, including Enterococcus species, were found, a stabilized ecosystem was established with Lactobacillus plantarum and Lactobacillus fermentum as the dominating LAB species. Compared with the combined outcome of culture-dependent and culture-independent identification techniques, the microarray data revealed a functional role for Lactococcus lactis in the early stage ecosystem and the dominance of Pediococcus pentosaceus in most of the fermentations, besides L. plantarum and L. fermentum. Consequently, metatranscriptome hybridization data obtained using an LAB functional gene microarray was shown to be an interesting alternative to microbiological analysis of the community dynamics of complex food ecosystems. PMID- 20581180 TI - Effect of the deletion of qmoABC and the promoter-distal gene encoding a hypothetical protein on sulfate reduction in Desulfovibrio vulgaris Hildenborough. AB - The pathway of electrons required for the reduction of sulfate in sulfate reducing bacteria (SRB) is not yet fully characterized. In order to determine the role of a transmembrane protein complex suggested to be involved in this process, a deletion in Desulfovibrio vulgaris Hildenborough was created by marker exchange mutagenesis that eliminated four genes putatively encoding the QmoABC complex and a hypothetical protein (DVU0851). The Qmo (quinone-interacting membrane-bound oxidoreductase) complex is proposed to be responsible for transporting electrons to the dissimilatory adenosine-5'-phosphosulfate reductase in SRB. In support of the predicted role of this complex, the deletion mutant was unable to grow using sulfate as its sole electron acceptor with a range of electron donors. To explore a possible role for the hypothetical protein in sulfate reduction, a second mutant was constructed that had lost only the gene that codes for the DVU0851 protein. The second constructed mutant grew with sulfate as the sole electron acceptor; however, there was a lag that was not present with the wild-type or complemented strain. Neither deletion strain was significantly impaired for growth with sulfite or thiosulfate as the terminal electron acceptor. Complementation of the Delta(qmoABC-DVU0851) mutant with all four genes or only the qmoABC genes restored its ability to grow by sulfate respiration. These results confirmed the prediction that the Qmo complex is in the electron pathway for sulfate reduction and revealed that no other transmembrane complex could compensate when Qmo was lacking. PMID- 20581181 TI - Freshwater suspended sediments and sewage are reservoirs for enterotoxin-positive Clostridium perfringens. AB - The release of fecal pollution into surface waters may create environmental reservoirs of feces-derived microorganisms, including pathogens. Clostridium perfringens is a commonly used fecal indicator that represents a human pathogen. The pathogenicity of this bacterium is associated with its expression of multiple toxins; however, the prevalence of C. perfringens with various toxin genes in aquatic environments is not well characterized. In this study, C. perfringens spores were used to measure the distribution of fecal pollution associated with suspended sediments in the nearshore waters of Lake Michigan. Particle-associated C. perfringens levels were greatest adjacent to the Milwaukee harbor and diminished in the nearshore waters. Species-specific PCR and toxin gene profiles identified 174 isolates collected from the suspended sediments, surface water, and sewage influent as C. perfringens type A. Regardless of the isolation source, the beta2 and enterotoxin genes were common among isolates. The suspended sediments yielded the highest frequency of cpe-carrying C. perfringens (61%) compared to sewage (38%). Gene arrangement of enterotoxin was investigated using PCR to target known insertion sequences associated with this gene. Amplification products were detected in only 9 of 90 strains, which suggests there is greater variability in cpe gene arrangement than previously described. This work presents evidence that freshwater suspended sediments and sewage influent are reservoirs for potentially pathogenic cpe-carrying C. perfringens spores. PMID- 20581182 TI - Interdomain conjugal transfer of DNA from bacteria to archaea. AB - Escherichia coli transforms the methanogenic archaeon Methanococcus maripaludis at frequencies ranging from 0.2 x 10(-6) to 2 x 10(-6) per recipient cell. Transformation requires cell-to-cell contact, oriT, and tra functions, is insensitive to DNase I, and otherwise displays hallmarks of conjugation. PMID- 20581183 TI - Rapid microarray-based genotyping of enterohemorrhagic Escherichia coli serotype O156:H25/H-/Hnt isolates from cattle and clonal relationship analysis. AB - Since enterohemorrhagic Escherichia coli (EHEC) isolates of serogroup O156 have been obtained from human diarrhea patients and asymptomatic carriers, we studied cattle as a potential reservoir for these bacteria. E. coli isolates serotyped by agglutination as O156:H25/H-/Hnt strains (n = 32) were isolated from three cattle farms during a period of 21 months and characterized by rapid microarray-based genotyping. The serotyping by agglutination of the O156 isolates was not confirmed in some cases by the results of DNA-based serotyping as only 25 of the 32 isolates were conclusively identified as O156:H25. In the multilocus sequence typing (MLST) analysis, all EHEC O156:H25 isolates were characterized as sequence type 300 (ST300) and ST688, which differ by a single-nucleotide exchange in the purA gene. Oligonucleotide microarrays allow simultaneous detection of a wider range of EHEC-associated and other E. coli virulence markers than other methods. All O156:H25 isolates showed a wide spectrum of virulence factors typical for EHEC. The stx(1) genes combined with the EHEC hlyA (hlyA(EHEC)) gene, the eae gene of the zeta subtype, as well as numerous other virulence markers were present in all EHEC O156:H25 strains. The behavior of eight different cluster groups, including four that were EHEC O156:H25, was monitored in space and time. Variations in the O156 cluster groups were detected. The results of the cluster analysis suggest that some O156:H25 strains had the genetic potential for a long persistence in the host and on the farm, while other strains did not. As judged by their pattern of virulence markers, E. coli O156:H25 isolates of bovine origin may represent a considerable risk for human infection. Our results showed that the miniaturized E. coli oligonucleotide arrays are an excellent tool for the rapid detection of a large number of virulence markers. PMID- 20581185 TI - Simultaneously discrete biomineralization of magnetite and tellurium nanocrystals in magnetotactic bacteria. AB - Magnetotactic bacteria synthesize intracellular magnetosomes comprising membrane enveloped magnetite crystals within the cell which can be manipulated by a magnetic field. Here, we report the first example of tellurium uptake and crystallization within a magnetotactic bacterial strain, Magnetospirillum magneticum AMB-1. These bacteria independently crystallize tellurium and magnetite within the cell. This is also highly significant as tellurite (TeO(3)(2 )), an oxyanion of tellurium, is harmful to both prokaryotes and eukaryotes. Additionally, due to its increasing use in high-technology products, tellurium is very precious and commercially desirable. The use of microorganisms to recover such molecules from polluted water has been considered as a promising bioremediation technique. However, cell recovery is a bottleneck in the development of this approach. Recently, using the magnetic property of magnetotactic bacteria and a cell surface modification technology, the magnetic recovery of Cd(2+) adsorbed onto the cell surface was reported. Crystallization within the cell enables approximately 70 times more bioaccumulation of the pollutant per cell than cell surface adsorption, while utilizing successful recovery with a magnetic field. This fascinating dual crystallization of magnetite and tellurium by magnetotactic bacteria presents an ideal system for both bioremediation and magnetic recovery of tellurite. PMID- 20581184 TI - Increased mutation frequency in redox-impaired Escherichia coli due to RelA- and RpoS-mediated repression of DNA repair. AB - Balancing of reducing equivalents is a fundamental issue in bacterial metabolism and metabolic engineering. Mutations in the key metabolic genes ldhA and pflB of Escherichia coli are known to stall anaerobic growth and fermentation due to a buildup of intracellular NADH. We observed that the rate of spontaneous mutation in E. coli BW25113 (DeltaldhA DeltapflB) was an order of magnitude higher than that in wild-type (WT) E. coli BW25113. We hypothesized that the increased mutation frequency was due to an increased NADH/NAD(+) ratio in this strain. Using several redox-impaired strains of E. coli and different redox conditions, we confirmed a significant correlation (P < 0.01) between intracellular NADH/NAD(+) ratio and mutation frequency. To identify the genetic basis for this relationship, whole-genome transcriptional profiles were compared between BW25113 WT and BW25113 (DeltaldhA DeltapflB). This analysis revealed that the genes involved in DNA repair were expressed at significantly lower levels in BW25113 (DeltaldhA DeltapflB). Direct measurements of the extent of DNA repair in BW25113 (DeltaldhA DeltapflB) subjected to UV exposure confirmed that DNA repair was inhibited. To identify a direct link between DNA repair and intracellular-redox ratio, the stringent-response-regulatory gene relA and the global-stress-response regulatory gene rpoS were deleted. In both cases, the mutation frequencies were restored to BW25113 WT levels. PMID- 20581186 TI - The genome sequence of the crenarchaeon Acidilobus saccharovorans supports a new order, Acidilobales, and suggests an important ecological role in terrestrial acidic hot springs. AB - Acidilobus saccharovorans is an anaerobic, organotrophic, thermoacidophilic crenarchaeon isolated from a terrestrial hot spring. We report the complete genome sequence of A. saccharovorans, which has permitted the prediction of genes for Embden-Meyerhof and Entner-Doudoroff pathways and genes associated with the oxidative tricarboxylic acid cycle. The electron transfer chain is branched with two sites of proton translocation and is linked to the reduction of elemental sulfur and thiosulfate. The genomic data suggest an important role of the order Acidilobales in thermoacidophilic ecosystems whereby its members can perform a complete oxidation of organic substrates, closing the anaerobic carbon cycle. PMID- 20581187 TI - Origin of the putrescine-producing ability of the coagulase-negative bacterium Staphylococcus epidermidis 2015B. AB - A multiplex PCR method, aimed at the detection of genes associated with biogenic amine production, identified the odc gene encoding ornithine decarboxylase in 1 of 15 strains of Staphylococcus epidermidis. The ability of the positive strain, S. epidermidis 2015B, to produce putrescine in vitro was demonstrated by high performance liquid chromatography (HPLC). In this strain, the odc gene was detected on plasmid DNA, suggesting that the ability to form putrescine is carried by a mobile element, which explains the fact that the trait is strain dependent within the S. epidermidis species. A 6,292-bp nucleotide sequence harboring the putative odc gene was determined. S. epidermidis ornithine decarboxylase (ODC) showed 60 to 65% sequence identity with known ODCs of Gram positive as well as Gram-negative bacteria. Downstream of the odc gene, a gene encoding a putative amino acid transporter was found that shared 59% sequence identity with the ornithine/putrescine exchanger (PotE) of Escherichia coli. Cloning and expression of the potE gene of S. epidermis 2015B in Lactococcus lactis demonstrated that the gene product transported ornithine and putrescine into the cells and efficiently exchanged putrescine for ornithine. Analysis of the flanking regions showed high identity levels with different S. epidermidis plasmid sequences, which would confirm the plasmidic location of the odc operon. It follows that the odc and potE gene pair encodes a putrescine-producing pathway in S. epidermis 2015B that was acquired through horizontal gene transfer. PMID- 20581188 TI - Pyrosequencing analysis of bacterial biofilm communities in water meters of a drinking water distribution system. AB - The applicability of 454 pyrosequencing to characterize bacterial biofilm communities from two water meters of a drinking water distribution system was assessed. Differences in bacterial diversity and composition were observed. A better understanding of the bacterial ecology of drinking water biofilms will allow for effective management of water quality in distribution systems. PMID- 20581189 TI - Integrated microbial survey analysis of prokaryotic communities for the PhyloChip microarray. AB - PhyloTrac is an integrated desktop application for analysis of PhyloChip microarray data. PhyloTrac combined with PhyloChip provides turnkey and comprehensive identification and analysis of bacterial and archaeal communities in complex environmental samples. PhyloTrac is free for noncommercial organizations and is available for all major operating systems at http://www.phylotrac.org/. PMID- 20581191 TI - Biocidal efficacy of copper alloys against pathogenic enterococci involves degradation of genomic and plasmid DNAs. AB - The increasing incidence of nosocomial infections caused by glycopeptide resistant enterococci is a global concern. Enterococcal species are also difficult to eradicate with existing cleaning regimens; they can survive for long periods on surfaces, thus contributing to cases of reinfection and spread of antibiotic-resistant strains. We have investigated the potential use of copper alloys as bactericidal surfaces. Clinical isolates of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium were inoculated onto copper alloy and stainless steel surfaces. Samples were assessed for the presence of viable cells by conventional culture, detection of actively respiring cells, and assessment of cell membrane integrity. Both species survived for up to several weeks on stainless steel. However, no viable cells were detected on any alloys following exposure for 1 h at an inoculum concentration of 10% of pregnancies. We performed a prospective cohort study investigating the association of maternal chromosomal damage in mid-pregnancy (20 weeks gestation) with pregnancy outcomes. Chromosome damage was measured using the cytokinesis-block micronucleus cytome (CBMNcyt) assay in peripheral blood lymphocytes. The odds ratio for PE and/or IUGR in a mixed cohort of low- and high risk pregnancies (N = 136) and a cohort of only high-risk pregnancies (N = 91) was 15.97 (P = 0.001) and 17.85 (P = 0.007), respectively, if the frequency of lymphocytes with micronuclei (MN) at 20 weeks gestation was greater than the mean + 2 SDs of the cohort. These results suggest that the presence of lymphocyte MN is significantly increased in women who develop PE and/or IUGR before the clinical signs or symptoms appear relative to women with normal pregnancy outcomes. The CBMNcyt assay may provide a new approach for the early detection of women at risk of developing these late pregnancy diseases and for biomonitoring the efficacy of interventions to reduce DNA damage, which may in turn ameliorate pregnancy outcome. PMID- 20581222 TI - Novel alpha-glucosidase from human gut microbiome: substrate specificities and their switch. AB - The human intestine harbors a large number of microbes forming a complex microbial community that greatly affects the physiology and pathology of the host. In the human gut microbiome, the enrichment in certain protein gene families appears to be widespread. They include enzymes involved in carbohydrate metabolism such as glucoside hydrolases of dietary polysaccharides and glycoconjugates. We report the crystal structures (wild type, 2 mutants, and a mutant/substrate complex) and the enzymatic activity of a recombinant alpha glucosidase from human gut bacterium Ruminococcus obeum. The first ever protein structures from this bacterium reveal a structural homologue to human intestinal maltase-glucoamylase with a highly conserved catalytic domain and reduced auxiliary domains. The alpha-glucosidase, a member of GH31 family, shows substrate preference for alpha(1-6) over alpha(1-4) glycosidic linkages and produces glucose from isomaltose as well as maltose. The preference can be switched by a single mutation at its active site, suggestive of widespread adaptation to utilization of a variety of polysaccharides by intestinal micro organisms as energy resources. PMID- 20581223 TI - Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. AB - TMEM16A was found recently to be a calcium-activated Cl(-) channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC(50) ~ 6 MUM and ~100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl(-) channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl(-) secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea. PMID- 20581224 TI - An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells. AB - Neuroblastoma (NB) is a pediatric cancer characterized by remarkable cell heterogeneity within the tumor nodules. Here, we demonstrate that the synthesis of a pol III-transcribed noncoding (nc) RNA (NDM29) strongly restricts NB development by promoting cell differentiation, a drop of malignancy processes, and a dramatic reduction of the tumor initiating cell (TIC) fraction in the NB cell population. Notably, the overexpression of NDM29 also confers to malignant NB cells an unpredicted susceptibility to the effects of antiblastic drugs used in NB therapy. Altogether, these results suggest the induction of NDM29 expression as possible treatment to increase cancer cells vulnerability to therapeutics and the measure of its synthesis in NB explants as prognostic factor of this cancer type. PMID- 20581225 TI - Molecular interaction of flagellar export chaperone FliS and cochaperone HP1076 in Helicobacter pylori. AB - Flagellar export chaperone FliS prevents premature polymerization of flagellins and is critical for flagellar assembly and bacterial colonization. Previously, a yeast 2-hybrid study identified various FliS-associated proteins in Helicobacter pylori, but the implications of these interactions are not known. Here we demonstrate the biophysical interaction of FliS (HP0753) and the uncharacterized protein HP1076 from H. pylori. HP1076 possesses a cochaperone activity that promotes the folding and chaperone activity of FliS. We further determined the crystal structures of FliS, HP1076, and the binary complex at 2.7, 1.8, and 2.7 A resolution, respectively. HP1076 adopts a helix-rich bundle structure and interestingly shares a similar fold with a flagellin homologue, hook-associated protein, and FliS. The FliS-HP1076 complex revealed an extensive electrostatic and hydrophobic binding interface, which is distinct from the flagellin binding pocket in FliS. The helical stacking interaction between HP1076 and FliS suggests that HP1076 stabilizes 2 alpha helices of FliS and therefore the overall structure of the bundle. Our findings provide new insights into flagellar export chaperones and may have implications for other secretion chaperones in the type III secretion system. PMID- 20581227 TI - Heterosexual romantic relationships inside of prison: partner status as predictor of loneliness, sexual satisfaction, and quality of life. AB - This study investigated the differences in loneliness, sexual satisfaction, and quality of life among three groups of prison inmates: inmates in a heterosexual romantic relationship with a fellow prisoner, inmates with a partner outside the prison, and inmates without a partner. In-person interviews with 70 male and 70 female inmates from the Topas Penitentiary (Spain) were conducted. These inmates lived in the same facility but in gender-segregated modules. After controlling for age, nationality, total time in prison, actual sentence time served, and estimated time to parole, the results showed a lower level of romantic loneliness, and a higher level of sexual satisfaction and global, psychological, and environment quality of life for the group of inmates with a heterosexual partner inside prison. These findings highlight the positive attributes associated with heterosexual romantic relationships between inmates inside the same prison. PMID- 20581226 TI - An essential component to brainstem cough gating identified in anesthetized guinea pigs. AB - Coughing protects and clears the airways and lungs of inhaled irritants, particulates, pathogens, and accumulated secretions. An initial urge to cough, and an almost binary output suggests gating mechanisms that encode and modulate this defensive reflex. Whether this "gate" has a physical location for the physiological barrier it poses to cough is unknown. Here we describe a critical component to cough gating, the central terminations of the cough receptors. A novel microinjection strategy defined coordinates for microinjection of glutamate receptor antagonists that nearly abolished cough evoked from the trachea and larynx in anesthetized guinea pigs while having no effect on basal respiratory rate and little or no effect on reflexes attributed to activating other afferent nerve subtypes. Comparable microinjections in adjacent brainstem locations (0.5-2 mm distal) were without effect on coughing. Subsequent transganglionic and dual tracing studies confirmed that the central terminations of the cough receptors and their primary relay neurons are found bilaterally within nucleus tractus solitarius (nTS), lateral to the commissural subnucleus and perhaps in the medial subnuclei. These synapses possess the physiological characteristics of a cough gate. Their localization should facilitate more mechanistic studies of the encoding and gating of cough. PMID- 20581228 TI - Measurement of the extreme ankle range of motion required by female ballet dancers. AB - Female ballet dancers require extreme ankle motion, especially plantar flexion, but research about measuring such motion is lacking. The purposes of this study were to determine in a sample of ballet dancers whether non-weight-bearing ankle range of motion is significantly different from the weight-bearing equivalent and whether inclinometric plantar flexion measurement is a suitable substitute for standard plantar flexion goniometry. Fifteen female ballet dancers (5 university, 5 vocational, and 5 professional dancers; age 21 +/- 3.0 years) volunteered. Subjects received 5 assessments on 1 ankle: non-weight-bearing goniometry dorsiflexion (NDF) and plantar flexion (NPF), weight-bearing goniometry in the ballet positions demi-plie (WDF) and en pointe (WPF), and non-weight-bearing plantar flexion inclinometry (IPF). Mean NDF was significantly lower than WDF (17 degrees +/- 1.3 degrees vs 30 degrees +/- 1.8 degrees , P < .001). NPF (77 degrees +/- 2.5 degrees ) was significantly lower than both WPF (83 degrees +/- 2.2 degrees , P = .01) and IPF (89 degrees +/- 1.6 degrees , P < .001), and WPF was significantly lower than IPF (P = .013). Dorsiflexion tended to decrease and plantar flexion tended to increase with increasing ballet proficiency. The authors conclude that assessment of extreme ankle motion in female ballet dancers is challenging, and goniometry and inclinometry appear to measure plantar flexion differently. PMID- 20581229 TI - Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? PMID- 20581230 TI - Immune cell reservoirs of persisting hepatitis C virus. PMID- 20581231 TI - Immunomodulation: a new approach to the therapy of cirrhosis? PMID- 20581232 TI - Collecting evidence for a stem cell hypothesis in HCC. PMID- 20581233 TI - Eicosapentaenoic acid and chemoprevention of FAP. PMID- 20581235 TI - A rare cause of ascites. PMID- 20581234 TI - Helicobacter pylori represses proton pump expression and inhibits acid secretion in human gastric mucosa. AB - BACKGROUND AND AIMS: Helicobacter pylori infection of gastric mucosa causes gastritis and transient hypochlorhydria, which may provoke emergence of a mucosal precancer phenotype; H pylori strains containing a cag pathogenicity island (PAI) augment cancer risk. Acid secretion is mediated by the catalytic alpha subunit of parietal cell H,K-ATPase (HKalpha). In AGS gastric epithelial cells, H pylori induces nuclear factor-kappaB (NF-kappaB) binding to and repression of transfected HKalpha promoter activity. This study sought to identify bacterial genes involved in HKalpha repression and to assess their impact on acid secretion. METHODS AND RESULTS: AGS cells transfected with an HKalpha promoter construct or human gastric body biopsies were infected with wild-type (wt) or isogenic mutant (IM) H pylori strains. AGS cell HKalpha promoter activity, and biopsy HKalpha mRNA, protein and H(+) secretory activity were measured by luminometry, reverse transcription-PCR, immunoblotting and extracellular acidification, respectively. Wt H pylori and DeltavacA, DeltaureA, Deltaslt and DeltaflaA IM strains repressed HKalpha promoter activity by approximately 50%, a DeltacagA IM strain repressed HKalpha by approximately 33%, and DeltacagE, DeltacagM and DeltacagL IM strains elicited no HKalpha repression. Wt H pylori infected biopsies had markedly reduced HKalpha mRNA and protein compared with IM strain infections or mock-infected controls. Histamine-stimulated, SCH28080 sensitive biopsy acid secretion was significantly inhibited by wt but not by DeltacagL IM H pylori infection compared with vehicle-only controls. CONCLUSIONS: It is concluded that H pylori cag PAI gene products CagE, CagM, CagL and, possibly, CagA are mechanistically involved in repression of HKalpha transcription. Further, acute H pylori infection of human gastric mucosa downregulates parietal cell H,K-ATPase expression, significantly inhibiting acid secretion. PMID- 20581236 TI - The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. AB - OBJECTIVE: Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material. DESIGN: Consensual processes undertaken by the IWG and following established guideline decision group methodologies. RESULTS AND CONCLUSION: This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available. PMID- 20581237 TI - Conditional Gata4 deletion in mice induces bile acid absorption in the proximal small intestine. AB - BACKGROUND AND AIMS: The transcription factor GATA4 is expressed throughout most of the small intestine except distal ileum, and restricts expression of the apical sodium-dependent bile acid transporter (ASBT), the rate-limiting intestinal bile acid transporter, to distal ileum. The hypothesis was tested that reduction of GATA4 activity in mouse small intestine results in an induction of bile acid transport in proximal small intestine sufficient to restore bile acid absorption and homeostasis after ileocaecal resection (ICR). METHODS: Bile acid homeostasis was characterised in non-surgical, sham or ICR mice using two recombinant Gata4 models in which Asbt expression is induced to different levels. RESULTS: Reduction of intestinal GATA4 activity resulted in an induction of ASBT expression, bile acid absorption and expression of bile acid-responsive genes in proximal small intestine, and a reduction of luminal bile acids in distal small intestine. While faecal bile acid excretion and bile acid pool size remained unchanged, the bile acid pool became more hydrophilic due to a relative increase in tauro-beta-muricholate absorption. Furthermore, proximal induction of Asbt in both Gata4 mutant models corrected ICR-associated bile acid malabsorption, reversing the decrease in bile acid pool size and increase in faecal bile acid excretion and hepatic cholesterol 7alpha-hydroxylase expression. CONCLUSIONS: Reduction of intestinal GATA4 activity induces bile acid absorption in proximal small intestine without inducing major changes in bile acid homeostasis. This induction is sufficient to correct bile acid malabsorption caused by ICR in mice. PMID- 20581238 TI - Targeting the proteasome: partial inhibition of the proteasome by bortezomib or deletion of the immunosubunit LMP7 attenuates experimental colitis. AB - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD), comprising Crohn s disease and ulcerative colitis, is characterised by chronic relapsing inflammation of the gut. Increased proteasome activity, associated with the expression of immunoproteasomes, was found to enhance proinflammatory signalling and thus promotes inflammation in patients with IBD. The aim of this study was to explore whether modulation of the proteasomal activity is a suitable therapeutic approach to limit inflammation in colitis. METHODS: This concept was assessed in two different experimental set-ups. Development of dextran sodium sulfate (DSS) induced colitis was tested (1) in lmp7(-/-) mice lacking the immunoproteasome subunit LMP7 and (2) in wild-type (WT) mice treated with the proteasome inhibitor bortezomib. RESULTS: Compared with WT mice, lmp7(-/-) mice develop significantly attenuated colitis due to reduced nuclear factor-kappaB (NF-kappaB) signalling in the absence of LMP7. Further, treatment with bortezomib revealed dose-dependent amelioration of DSS-induced inflammation. In both approaches modulation of the proteasome activity limited the secretion of proinflammatory cytokines and chemokines. Consequently, infiltration of the colon by neutrophils and expansion of inflammatory T helper 1 (Th1) and Th17 T cells was diminished and thus prevented excessive tissue damage. CONCLUSIONS: It was demonstrated that modulation of the proteasome activity is effective in attenuating experimental colitis. The results reveal that reduction of the proteasome activity either by partial inhibition with bortezomib or by specifically targeting the immunoproteasome subunit LMP7 is a suitable treatment of intestinal inflammation. PMID- 20581239 TI - Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/beta-catenin signal via ISGylation of beta catenin. AB - BACKGROUND AND AIMS: 90K, a tumour-associated glycoprotein, interacts with galectins and has roles in host defence by augmenting the immune response, but the serum 90K level was suggested to indicate poor prognosis in several cancers. The cellular mechanisms of 90K action on colorectal cancer (CRC) cell motility and its effect on CRC progression were investigated. METHODS: The impact of 90K was analysed by combining cell cultures, in vitro assays, and immunohistochemistry. RESULTS: Secreted 90K suppresses CRC cell invasion, but this action of 90K is masked through binding with extracellular galectins. A novel pathway is identified comprising a secretory 90K and a CD9/CD82 tetraspanin web; in this pathway, 90K interacts with CD9/CD82, suppresses the Wnt/beta catenin signal via a novel proteasomal-ubiquitination mechanism of beta-catenin that is dependent on ISG15 (interferon-stimulated gene-15) modification (ISGylation) but not on glycogen synthase kinase 3beta (GSK-3beta) and Siah/Adenomatous polyposis coli (APC). In a syngeneic mouse colon tumour model, tumour growth and lung metastasis were increased with 90K knockdown. In colon tissues from stage IV human CRC and invading cancer cells of corresponding metastatic liver tissues, in which beta-catenin and galectin expression was higher, immunostained 90K and CD9/CD82 were lower than in adjacent hepatic tissues or colon tissues from stage I. CONCLUSIONS: 90K itself has antitumour activity in CRC cells via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of beta-catenin when it interacts with CD9/CD82, but is downregulated in advanced CRC tissues. The data suggest a strategy of strengthening this novel pathway with concomitant knockdown of galectins as a potential therapeutic approach to CRC progression. PMID- 20581240 TI - Emergency management of an uncommon abdominal pain. PMID- 20581241 TI - Intratumoral T cell infiltration, MHC class I and STAT1 as biomarkers of good prognosis in colorectal cancer. AB - OBJECTIVE: To evaluate immunosurveillance/editing in colorectal cancer. DESIGN: Transformation stimulates the production of interferon gamma (IFNgamma) which signals via the IFNgamma receptor (IFNGR1) on tumours. This results in stimulation of nuclear STAT1 (nSTAT1), inhibition of tumour growth and upregulation of major histocompatibility complex (MHC) while promoting T cell extravasation. In contrast, downregulation of MHC class I by allele loss results in loss of T cell recognition. A tissue microarray of 462 colorectal tumours with mean follow-up of 42 months (range 1-116) was stained by immunohistochemistry for markers which predict immunosurveillance/editing. RESULTS: The presence of a high level of intratumoral T cells (ITTC) correlated with improved survival compared with a low level of ITTC, with a mean difference in survival of 16.3 months (p=0.006). There was a direct correlation between nSTAT1 expression and ITTC (p<0.001). Patients whose tumours had a high level of ITTC and nSTAT1 survived 20 months longer than those whose tumours had a low level of ITTC and no nSTAT1. A strong correlation was seen between ITTC and MHC class I expression (p=0.0002). A mean survival advantage of 26.1 months was seen in patients whose tumours had strong MHC I expression and high levels of ITTC over those who had weak MHC I and low levels of ITTC (log-rank test=12.023, p=0.034). Both MHC I and ITTC are independent predictors of good survival. CONCLUSIONS: ITTC, nSTAT1 and strong MHC class I expression on tumours identify patients with improved survival and an intact tumour immune system that may benefit from immunotherapy. Conversely, loss of these markers identifies patients whose tumours have escaped immunosurveillance and are unlikely to benefit from immunotherapy. PMID- 20581242 TI - An unexpected target. Intussusception of the small intestine. PMID- 20581243 TI - Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis. AB - BACKGROUND: The Model for End Stage Liver Disease (MELD) predicts mortality in end stage liver disease. Incorporation of serum sodium into the MELD may improve diagnostic accuracy in decompensated patients with ascites. However, other complications of cirrhosis are not reflected. This study investigates whether quantitative liver function tests predict survival and increase prognostic accuracy of the MELD. METHODS: 604 patients with suspected cirrhosis were staged clinically and haemodynamically. Galactose-elimination-capacity, sorbitol clearance, lidocaine metabolism and indocyanin green (ICG) half life were determined. Survival was the primary end point of the study. Prognostic effects of individual parameters were calculated using Cox regression models and ROC curves. RESULTS: 321 patients on standard pharmacological and endoscopic treatment (PET) and 74 patients undergoing transjugular portosystemic shunting (TIPS) were studied. Of all quantitative liver function tests, ICG half life was the most accurate in predicting survival. Upon incorporation into the MELD, it modified the score in patients with PET up to 35 points. Clinically relevant changes to the score, however, occurred in patients with a MELD score between 10 and 30, allowing an objective prognostic discrimination of individual survival based on laboratory liver function and blood flow. The MELD-ICG was validated in the second cohort of patients undergoing TIPS implantation. CONCLUSION: ICG had the highest predictive value of the examined tests. Its incorporation into the MELD adds an estimation of liver blood flow and renders the new score MELD-ICG more accurate in predicting survival in intermediate to advanced cirrhosis than the MELD and MELD-Na. PMID- 20581244 TI - Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. AB - BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) have increased mortality and liver-related complications. In contrast, simple steatosis is considered benign and non-progressive. OBJECTIVE: To investigate disease progression in patients with different degrees of non-alcoholic fatty liver disease (NAFLD) activity. DESIGN: Prospective longitudinal hospital-based cohort study. PATIENTS: Fifty-two patients (age 44+/-9 years) with biopsy-proven NAFLD had liver biopsies repeated at month 36. RESULTS: Among 13 patients with simple steatosis at baseline, 2 (15%) had a normal liver at month 36, 3 (23%) continued to have simple steatosis, 5 (39%) developed borderline NASH and 3 (23%) developed NASH. Among 22 patients with borderline NASH at baseline, 4 (18%) had simple steatosis and 13 (59%) had borderline NASH at month 36, while 5 (23%) developed NASH. Among 17 patients with NASH at baseline, 10 (59%) continued to have NASH and 6 (35%) had borderline NASH at month 36. Only 1 (6%) patient regressed to simple steatosis. Overall, 14 (27%) patients had fibrosis progression, 25 (48%) had static disease, and 13 (25%) had fibrosis regression. Reduction in body mass index and waist circumference was independently associated with non-progressive disease activity and fibrosis. The baseline serum levels and month 36 changes in adiponectin, tumour necrosis factor alpha, interleukin 6 and leptin were not associated with disease progression. Serum cytokeratin-18 fragment level reflected disease activity and its change correlated with the change in NAFLD activity score (R=0.51, p<0.001). CONCLUSIONS: Patients with simple steatosis may still develop NASH and fibrosis progression. Weight reduction is associated with non-progressive disease. All patients with NAFLD should undergo periodic assessment and lifestyle modification. PMID- 20581245 TI - Peutz-Jeghers syndrome: a systematic review and recommendations for management. AB - Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis. PMID- 20581246 TI - TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update. AB - Refractory ascites is a frequent complication of advanced cirrhosis and is associated with hepatorenal syndrome and hepatic hydrothorax. Large volume paracentesis and pleurodesis are regarded as first-line treatments in patients who do not respond adequately to diuretics. These treatments, however, do not prevent recurrence and carry the risk of worsening of the circulatory dysfunction leading to hepatorenal syndrome. The transjugular intrahepatic portosystemic shunt (TIPS) has been proposed as an alternative to paracentesis. TIPS reduces the rate of ascites recurrence mainly due to the reduction in the filtration pressure. In addition, TIPS results in a positive effect on renal function, including hepatorenal syndrome, demonstrated by a rapid increase in urinary sodium excretion, urinary volume, and improvement in plasma creatinine concentration. Furthermore, plasma renin activity, aldosterone, and noradrenalin concentrations improve gradually after TIPS insertion suggesting a positive effect on systemic underfilling, the factor of hepatorenal syndrome. As demonstrated recently in two meta-analyses including five randomised studies, TIPS also improves survival when compared with paracentesis. However, the evidence is based on relatively few studies with only 305 patients included. The positive effects of the TIPS are opposed by an increased frequency and severity of episodes of hepatic encephalopathy which may be reduced by both patient selection and reduced shunt diameter. Based on the present knowledge the recommended hierarchy of treatments for refractory ascites may be reconsidered upgrading TIPS in suitable candidates. PMID- 20581247 TI - Systemic microRNAs: novel biomarkers for colorectal and other cancers? PMID- 20581250 TI - Gastric retention and wireless capsule endoscopy in adults: a modified technique for direct duodenal deployment. PMID- 20581252 TI - Surveillance in individuals at high risk of pancreatic cancer: too early to tell? PMID- 20581255 TI - A brief nap is beneficial for human route-learning: The role of navigation experience and EEG spectral power. AB - Here, we examined the effect of a daytime nap on changes in virtual maze performance across a single day. Participants either took a short nap or remained awake following training on a virtual maze task. Post-training sleep provided a clear performance benefit at later retest, but only for those participants with prior experience navigating in a three-dimensional (3D) environment. Performance improvements in experienced players were correlated with delta-rich stage 2 sleep. Complementing observations that learning-related brain activity is reiterated during post-navigation NREM sleep in rodents, the present data demonstrate that NREM sleep confers a performance advantage for spatial memory in humans. PMID- 20581257 TI - Incinerators, birth defects and the legacy of Thomas Bayes. PMID- 20581256 TI - Boron toxicity tolerance in barley through reduced expression of the multifunctional aquaporin HvNIP2;1. AB - Boron (B) toxicity is a significant limitation to cereal crop production in a number of regions worldwide. Here we describe the cloning of a gene from barley (Hordeum vulgare), underlying the chromosome 6H B toxicity tolerance quantitative trait locus. It is the second B toxicity tolerance gene identified in barley. Previously, we identified the gene Bot1 that functions as an efflux transporter in B toxicity-tolerant barley to move B out of the plant. The gene identified in this work encodes HvNIP2;1, an aquaporin from the nodulin-26-like intrinsic protein (NIP) subfamily that was recently described as a silicon influx transporter in barley and rice (Oryza sativa). Here we show that a rice mutant for this gene also shows reduced B accumulation in leaf blades compared to wild type and that the mutant protein alters growth of yeast (Saccharomyces cerevisiae) under high B. HvNIP2;1 facilitates significant transport of B when expressed in Xenopus oocytes compared to controls and to another NIP (NOD26), and also in yeast plasma membranes that appear to have relatively high B permeability. We propose that tolerance to high soil B is mediated by reduced expression of HvNIP2;1 to limit B uptake, as well as by increased expression of Bot1 to remove B from roots and sensitive tissues. Together with Bot1, the multifunctional aquaporin HvNIP2;1 is an important determinant of B toxicity tolerance in barley. PMID- 20581258 TI - More pain, less gain. PMID- 20581259 TI - Maternal residence near municipal waste incinerators and the risk of urinary tract birth defects. AB - OBJECTIVES: Waste incineration releases a mixture of chemicals with high embryotoxic potential, including heavy metals and dioxins/furans, into the atmosphere. In a previous ecological study we found an association between the risk of urinary tract birth defects and residence in the vicinity of municipal solid waste incinerators (MSWIs). The objective of the present study was to specifically test this association. METHODS: A population-based case-control study compared 304 infants with urinary tract birth defects diagnosed in the Rhone-Alpes region (2001-2003) with a random sample of 226 population controls frequency-matched for infant sex and year and district of birth. Exposure to dioxins in early pregnancy at the place of residence, used as a tracer of the mixture released by 21 active waste incinerators, was predicted with second generation Gaussian modelling (ADMS3 software). Other industrial emissions of dioxins, population density and neighbourhood deprivation were also assessed. Individual risk factors including consumption of local food were obtained by interviews with 62% of the case and all control families. RESULTS: Risk was increased for mothers exposed to dioxins above the median at the beginning of pregnancy (OR 2.95, 95% CI 1.47 to 5.92 for dioxin deposits). When only interviewed cases were considered, risk estimates decreased mainly because the non-interviewed cases were more likely to live in exposed residential environments (OR 2.05, 95% CI 0.92 to 4.57). The results suggest that consumption of local food modifies this risk. CONCLUSIONS: This study confirms our previous observation of a link between the risk of urinary tract birth defects and exposure to MSWI emissions in early pregnancy and illustrates the effect of participation bias on risk estimates of environmental health impacts. PMID- 20581260 TI - Cancer incidence among women flax textile manufacturing workers in Lithuania. AB - OBJECTIVE: To determine site-specific cancer incidence among women spinning weaving and dyeing-finishing workers in the largest flax textile factory in Lithuania. METHOD: The cancer incidence of a cohort of 3447 women workers from a flax textile factory was investigated for the period 1978-2002. All subjects were employed at the plant in the period 1957-2000 for a minimum of 12 months. Standardised incidence ratios (SIRs) were estimated by use of the corresponding national rates. SIRs were calculated for the spinning-weaving and dyeing finishing work categories, and for two durations of employment categories (<10 years, > or =10 years). RESULTS: The cancer SIRs among spinning-weaving and dyeing-finishing workers were 0.84 (95% CI 0.69 to 1.00) and 0.90 (95% CI 0.52 to 1.44). An incidence deficit for non-melanoma skin cancer was found for the spinning-weaving unit (SIR 0.45, 95% CI 0.18 to 0.92). The risk of oral cavity and pharynx cancer was significantly increased in spinning-weaving unit workers with <10 years of employment (SIR 5.71, 95% CI 1.56 to 14.60). A significant excess of thyroid cancer and nervous system cancer was found among dyeing finishing workers. CONCLUSIONS: The overall cancer and non-melanoma skin cancer incidence rate among flax spinning-weaving workers was lower compared with the Lithuanian population. The present findings lend some support to an excess of thyroid and nervous system cancers among dyeing-finishing workers and of oral cavity and pharynx cancer in spinning-weaving workers. PMID- 20581261 TI - Can smoking cessation be successfully promoted among hospitality workers? Results of a pilot intervention. PMID- 20581262 TI - Occupational asthma to caddis flies (Phryganeiae). PMID- 20581263 TI - Why are barn owls a model system for sound localization? PMID- 20581264 TI - Ant traffic rules. AB - Many animals take part in flow-like collective movements. In most species, however, the flow is unidirectional. Ants are one of the rare group of organisms in which flow-like movements are predominantly bidirectional. This adds to the difficulty of the task of maintaining a smooth, efficient movement. Yet, ants seem to fare well at this task. Do they really? And if so, how do such simple organisms succeed in maintaining a smooth traffic flow, when even humans experience trouble with this task? How does traffic in ants compare with that in human pedestrians or vehicles? The experimental study of ant traffic is only a few years old but it has already provided interesting insights into traffic organization and regulation in animals, showing in particular that an ant colony as a whole can be considered as a typical self-organized adaptive system. In this review we will show that the study of ant traffic can not only uncover basic principles of behavioral ecology and evolution in social insects but also provide new insights into the study of traffic systems in general. PMID- 20581265 TI - Northern gannets anticipate the spatio-temporal occurrence of their prey. AB - Seabirds, as other marine top predators, are often assumed to forage in an unpredictable environment. We challenge this concept and test the hypothesis that breeding Northern gannets (Morus bassanus) anticipate the spatio-temporal occurrence of their prey in the English Channel. We analyzed 23 foraging tracks of Northern gannets breeding on Rouzic Island (Brittany) that were recorded using GPS loggers during 2 consecutive years. All birds commuted between the breeding colony and foraging areas located at a mean distance of 85 km and 72 km (in 2005 and 2006, respectively) from the colony. Mean linearity indices of the outbound and inbound trips were between 0.83 and 0.87, approaching a beeline path to and from the foraging area. Additional parameters (flight speed, and number and duration of stopovers at sea) for the outbound and inbound trip were not statistically different, indicating that birds are capable of locating these feeding areas in the absence of visual clues, and to pin-point their breeding site when returning from the sea. Our bearing choice analysis also revealed that gannets anticipate the general direction of their foraging area during the first 30 min and the first 10 km of the trip. These results strongly suggest that birds anticipate prey location, rather than head into a random direction until encountering a profitable area. Further investigations are necessary to identify the mechanisms involved in seabird resource localization, such as sensorial abilities, memory effects, public information or a combination of these factors. PMID- 20581266 TI - The role of the anterior lateral eyes in the vision-based behaviour of jumping spiders. AB - Jumping spiders, or salticids, sample their environment using a combination of two types of eyes. The forward-facing pair of 'principal' eyes have narrow fields of view, but exceptional spatial resolution, while the two or three pairs of 'secondary' eyes have wide fields of view and function especially well as motion analysers. Motion detected by the secondary eyes may elicit an orienting response, whereupon the object of interest is examined further using the high acuity principal eyes. The anterior lateral (AL) eyes are particularly interesting, as they are the only forward-facing pair of secondary eyes. In this study, we aimed to determine characteristics of stimuli that elicit orienting responses mediated by the AL eyes. After covering all eyes except the AL eyes, we measured orienting responses to dot stimuli that varied in size and contrast, and moved at different speeds. We found that all stimulus parameters had significant effects on orientation propensity. When tethered flies were used as prey, we found that visual information from the AL eyes alone was sufficient to elicit stalking behaviour. These results suggest that, in terms of overall visual processing, the relevance of spatial vision in the AL eyes has been underestimated in the literature. Our results also show that female spiders are significantly more responsive than males. We found that hunger caused similar increases in orientation propensity in the two sexes, but females responded more often than males both when sated and when hungry. A higher propensity by females to orient toward moving objects may be related to females tending to experience higher nutritional demands than males. PMID- 20581267 TI - Postprandial metabolism of Pacific bluefin tuna (Thunnus orientalis). AB - Specific dynamic action (SDA) is defined as the energy expended during ingestion, digestion, absorption and assimilation of a meal. This study presents the first data on the SDA response of individual tunas of any species. Juvenile Pacific bluefin tunas (Thunnus orientalis; body mass 9.7-11.0 kg; N=7) were individually fed known quantities of food consisting primarily of squid and sardine (meal energy range 1680-8749 kJ, approximately 4-13% of tuna body mass). Oxygen consumption rates (M(O2)) were measured in a swim tunnel respirometer during the postprandial period at a swimming speed of 1 body length (BL) s(-1) and a water temperature of 20 degrees C. was markedly elevated above routine levels in all fish following meal consumption [routine metabolic rate (RMR)=174+/-9 mg kg(-1) h(-1)]. The peak M(O2) during the SDA process ranged from 250 to 440 mg kg(-1) h( 1) (1.5-2.3 times RMR) and was linearly related to meal energy content. The duration of the postprandial increment in M(O2) ranged from 21 h to 33 h depending upon meal energy content. Consequently, the total energy used in SDA increased linearly with meal energy and ranged from 170 kJ to 688 kJ, such that the SDA process accounted for 9.2+/-0.7% of ingested energy across all experiments. These values suggest rapid and efficient food conversion in T. orientalis in comparison with most other fishes. Implanted archival temperature tags recorded the increment in visceral temperature (T(V)) in association with SDA. M(O2) returned to routine levels at the end of the digestive period 2-3 h earlier than T(V). The qualitative patterns in M(O2) and T(V) during digestion were similar, strengthening the possibility that archival measurements of T(V) can provide new insight into the energetics and habitat utilization of free swimming bluefin in the natural environment. Despite efficient food conversion, SDA is likely to represent a significant component of the daily energy budget of wild bluefin tunas due to a regular and high ingestion of forage. PMID- 20581268 TI - Jumping mechanisms and performance of pygmy mole crickets (Orthoptera, Tridactylidae). AB - Pygmy mole crickets live in burrows at the edge of water and jump powerfully to avoid predators such as the larvae and adults of tiger beetles that inhabit the same microhabitat. Adults are 5-6 mm long and weigh 8 mg. The hind legs are dominated by enormous femora containing the jumping muscles and are 131% longer than the body. The ratio of leg lengths is: 1:2.1:4.5 (front:middle:hind, respectively). The hind tarsi are reduced and their role is supplanted by two pairs of tibial spurs that can rotate through 180 deg. During horizontal walking the hind legs are normally held off the ground. Jumps are propelled by extension of the hind tibiae about the femora at angular velocities of 68,000 deg s(-1) in 2.2 ms, as revealed by images captured at rates of 5000 s(-1). The two hind legs usually move together but can move asynchronously, and many jumps are propelled by just one hind leg. The take-off angle is steep and once airborne the body rotates backwards about its transverse axis (pitch) at rates of 100 Hz or higher. The take-off velocity, used to define the best jumps, can reach 5.4 m s(-1), propelling the insect to heights of 700 mm and distances of 1420 mm with an acceleration of 306 g. The head and pronotum are jerked rapidly as the body is accelerated. Jumping on average uses 116 microJ of energy, requires a power output of 50 mW and exerts a force of 20 mN. In jumps powered by one hind leg the figures are about 40% less. PMID- 20581269 TI - Co-variation between autotrophy and heterotrophy in the Mediterranean coral Cladocora caespitosa. AB - This study quantifies the relative contributions of autotrophy and heterotrophy to the energy budget of the temperate scleractinian species Cladocora caespitosa Linnaeus 1767. Colonies were incubated under different light and feeding regimes, and changes in carbon acquisition through photosynthesis and feeding were measured during a 2-month time period. This approach allowed us to quantify the rate at which adjustments to physiology occurred, as well as the magnitude of up- or downregulation of both feeding modes. In addition, we explored how shifts in carbon acquisition mode influenced tissue biomass (protein content), energy stores (lipid content) and colony growth (calcification). Increases in feeding capacity during prolonged exposure to darkness were correlated with decreases in photosynthetic capacity. However, feeding effort did not decrease when photosynthesis was high. In fact, feeding was maximal under high light conditions when food was not available. During starvation, colonies used their lipid stores to partially meet their metabolic requirements. Colonies kept in low light used nutrients from feeding to supplement calcification, whereas those kept at high light converted carbon from feeding into tissue biomass. This work provides the first estimates of rates of adjustment of heterotrophic feeding capacity in a Mediterranean scleractinian coral. For the study species, flexibility in carbon acquisition through heterotrophy was approximately equal to flexibility in photosynthesis both in magnitude and in the rate at which physiological adjustments occurred. The ability to alter feeding effort rapidly and strongly may explain the wide depth distribution of C. caespitosa, and its ability to survive in turbid coastal waters where light is often limited. PMID- 20581270 TI - Controlling anoxic tolerance in adult Drosophila via the cGMP-PKG pathway. AB - In this study we identify a cGMP-dependent protein kinase (PKG) cascade as a biochemical pathway critical for controlling low-oxygen tolerance in the adult fruit fly, Drosophila melanogaster. Even though adult Drosophila can survive in 0% oxygen (anoxia) environments for hours, air with less than 2% oxygen rapidly induces locomotory failure resulting in an anoxic coma. We use natural genetic variation and an induced mutation in the foraging (for) gene, which encodes a Drosophila PKG, to demonstrate that the onset of anoxic coma is correlated with PKG activity. Flies that have lower PKG activity demonstrate a significant increase in time to the onset of anoxic coma. Further, in vivo pharmacological manipulations reveal that reducing either PKG or protein phosphatase 2A (PP2A) activity increases tolerance of behavior to acute hypoxic conditions. Alternatively, PKG activation and phosphodiesterase (PDE5/6) inhibition significantly reduce the time to the onset of anoxic coma. By manipulating these targets in paired combinations, we characterized a specific PKG cascade, with upstream and downstream components. Further, using genetic variants of PKG expression/activity subjected to chronic anoxia over 6 h, approximately 50% of animals with higher PKG activity survive, while only approximately 25% of those with lower PKG activity survive after a 24 h recovery. Therefore, in this report we describe the PKG pathway and the differential protection of function vs survival in a critically low oxygen environment. PMID- 20581271 TI - Selection of entomopathogenic nematodes for enhanced responsiveness to a volatile root signal helps to control a major root pest. AB - The efficacy of natural enemies as biological control agents against insect pests can theoretically be enhanced by artificial selection for high responsiveness to foraging cues. The recent discovery that maize roots damaged by the western corn rootworm (WCR) emit a key attractant for insect-killing nematodes has opened the way to explore whether a selection strategy can improve the control of root pests. The compound in question, (E)-beta-caryophyllene, is only weakly attractive to Heterorhabditis bacteriophora, one of the most infectious nematodes against WCR. To overcome this drawback, we used a six-arm below-ground olfactometer to select for a strain of H. bacteriophora that is more readily attracted to (E)-beta-caryophyllene. After six generations of selection, the selected strain responded considerably better and moved twice as rapidly towards a (E)-beta-caryophyllene source than the original strain. There was a minor trade off between this enhanced responsiveness and nematode infectiveness. Yet, in subsequent field tests, the selected strain was significantly more effective than the original strain in reducing WCR populations in plots with a maize variety that releases (E)-beta-caryophyllene, but not in plots with a maize variety that does not emit this root signal. These results illustrate the great potential of manipulating natural enemies of herbivores to improve biological pest control. PMID- 20581272 TI - Effects of nutritional condition on spring migration: do migrants use resource availability to keep pace with a changing world? AB - Because of their reliance on temporally predictable resources across large spatial scales, migratory birds may be especially vulnerable to anthropogenic climate and land-use changes. Although some long-distance migrants appear unable to adjust to phenological shifts on their wintering grounds, several short- and medium-distance migrants appear to have altered the timing and/or distance of their yearly movements to compensate for the environmental effects of global warming. Which environmental cues are responsible for stimulating these adjustments is an unanswered question, although most studies have focused on weather conditions. Here, we present a novel field experiment that demonstrates that an alternative cue, food availability, may be a crucial link between local conditions on the wintering grounds and the timing of spring departure. When we provided dark-eyed juncos (Junco hyemalis) with an abundant food supply in early spring, we observed an advance in migration, especially among individuals that increased their mass and fat stores in response to the treatment. This finding indicates a simple mechanism by which short-distance migrants may calibrate their migration behavior such that arrival on the breeding grounds and initiation of reproduction are in sync with resource availability. PMID- 20581273 TI - The ultrastructure and contractile properties of a fast-acting, obliquely striated, myosin-regulated muscle: the funnel retractor of squids. AB - We investigated the ultrastructure, contractile properties, and in vivo length changes of the fast-acting funnel retractor muscle of the long-finned squid Doryteuthis pealeii. This muscle is composed of obliquely striated, spindle shaped fibers ~3 mum across that have an abundant sarcoplasmic reticulum, consisting primarily of membranous sacs that form 'dyads' along the surface of each cell. The contractile apparatus consists of 'myofibrils' approximately 0.25 0.5 microm wide in cross section arrayed around the periphery of each cell, surrounding a central core that contains the nucleus and large mitochondria. Thick myofilaments are approximately 25 nm in diameter and approximately 2.8 microm long. 'Dense bodies' are narrow, resembling Z lines, but are discontinuous and are not associated with the cytoskeletal fibrillar elements that are so prominent in slower obliquely striated muscles. The cells approximate each other closely with minimal intervening intercellular connective tissue. Our physiological experiments, conducted at 17 degrees C, showed that the longitudinal muscle fibers of the funnel retractor were activated rapidly (8 ms latent period following stimulation) and generated force rapidly (peak twitch force occurred within 50 ms). The longitudinal fibers had low V(max) (2.15 +/ 0.26 L(0) s(-1), where L(0) was the length that generated peak isometric force) but generated relatively high isometric stress (270+/-20 mN mm(-2) physiological cross section). The fibers exhibited a moderate maximum power output (49.9 W kg( 1)), compared with vertebrate and arthropod cross striated fibers, at a V/V(max) of 0.33+/-0.044. During ventilation of the mantle cavity and locomotion, the funnel retractor muscle operated in vivo over a limited range of strains (+0.075 to -0.15 relative to resting length, L(R)) and at low strain rates (from 0.16 to 0.91 L(R) s(-1) ), corresponding to a range of V/V(max) from 0.073 to 0.42. During the exhalant phase of the jet the range of strains was even narrower: maximum range less than +/-0.04, with the muscle operating nearly isometrically during ventilation and slow, arms-first swimming. The limited length operating range of the funnel retractor muscles, especially during ventilation and slow jetting, suggests that they may act as muscular struts. PMID- 20581274 TI - Buccal pumping mechanics of Xenopus laevis tadpoles: effects of biotic and abiotic factors. AB - Biotic factors such as body size and shape have long been known to influence kinematics in vertebrates. Movement in aquatic organisms can also be strongly affected by abiotic factors such as the viscosity of the medium. We examined the effects of both biotic factors and abiotic factors on buccal pumping kinematics in Xenopus tadpoles using high-speed imaging of an ontogenetic series of tadpoles combined with experimental manipulation of the medium over a 10-fold range of viscosity. We found influences of both biotic and abiotic factors on tadpole movements; absolute velocities and excursions of the jaws and hyoid were greater in higher viscosity fluid but durations of movements were unaffected. Smaller tadpoles have relatively wider heads and more robust hyoid muscles used in buccal expansion and compression. Lever arm ratios were found to be constant at all sizes; therefore, smaller tadpoles have relatively higher resolved muscle forces and, like tadpoles in more viscous medium, displayed higher absolute velocities of jaw and hyoid movements. Nonetheless, small tadpoles drew in water at lower Reynolds numbers (Re) than predicted by kinematics, due to negative allometry of the buccal pump. Finally, tadpoles transitioned from a flow regime dominated by viscous forces (Re=2) to an intermediate regime (Re=106). PMID- 20581275 TI - Cave-dwelling bats do not avoid TMT and 2-PT - components of predator odour that induce fear in other small mammals. AB - Recognition and avoidance of predators is fundamental for the survival of prey animals. Here we conducted the first study assessing chemosensory predator recognition in cave-dwelling bats. We used a Y-maze approach to test the reaction of greater mouse-eared bats (Myotis myotis) to two synthetically derived components of predator odour (2,4,5-trimethyl-3-thiazoline, TMT, a component of fox faeces scent; and 2-propylthietane, 2-PT, a component of mustelid scent) and to the natural scent of the least weasel (Mustela nivalis). It is well documented that rodents and several other small mammals show strong and at least partly innate fear reactions when confronted with these odorants. By contrast, the bats did not show any avoidance or fear reaction, despite the fact that relatively high odorant concentrations were presented. Furthermore, they did not react differently towards predator scent and towards acrid but otherwise neutral odours (basil or goat). The number of entries into in the Y-maze arm with the odour source and the time spent in this arm as well as the bats' overall exploratory activity and several other behavioural variables were not affected by the odour treatments. Generally, the sense of smell is well developed in bats and plays an important role in bat behavioural ecology. It is thus somewhat surprising that the bats did not show any avoidance reaction to predator scent, even though direct contact with a mustelid or fox would result in death. We discuss ecological explanations that might have prevented bats from evolving olfactory predatory recognition and avoidance. PMID- 20581276 TI - A syntax of hoverfly flight prototypes. AB - Hoverflies such as Eristalis tenax Linnaeus are known for their distinctive flight style. They can hover on the same spot for several seconds and then burst into movement in apparently any possible direction. In order to determine a quantitative and structured description of complex flight manoeuvres, we searched for a set of repeatedly occurring prototypical movements (PMs) and a set of rules for their ordering. PMs were identified by applying clustering algorithms to the translational and rotational velocities of the body of Eristalis during free flight sequences. This approach led to nine stable and reliable PMs, and thus provided a tremendous reduction in the complexity of behavioural description. This set of PMs together with the probabilities of transition between them constitute a syntactical description of flight behaviour. The PMs themselves can be roughly segregated into fast rotational turns (saccades) and a variety of distinct translational movements (intersaccadic intervals). We interpret this segregation as reflecting an active sensing strategy which facilitates the extraction of spatial information from retinal image displacements. Detailed analysis of saccades shows that they are performed around all rotational axes individually and in all possible combinations. We found the probability of occurrence of a given saccade type to depend on parameters such as the angle between the long body axis and the direction of flight. PMID- 20581277 TI - Cold-acclimation-induced non-shivering thermogenesis in birds is associated with upregulation of avian UCP but not with innate uncoupling or altered ATP efficiency. AB - Despite their lack of brown adipose tissue, some bird species develop regulatory non-shivering thermogenesis (NST) of skeletal muscle origin in response to cold acclimation. Mechanisms involved in avian NST are still unclear but may involve reduced energetic coupling in skeletal muscle mitochondria through the expression of an avian homologue of mammalian uncoupling proteins. The aim of this work was to investigate whether the expression of avian uncoupling protein (avUCP) would correlate with the capacity for cold-induced muscle NST. Various levels of cold acclimation were obtained by rearing 1-week-old ducklings (Cairina moschata) for 4 weeks at three different ambient temperatures (25 degrees C, 11 degrees C or 4 degrees C). Muscle NST was measured by simultaneous recordings of metabolic rate and electromyographic activity (gastrocnemius muscle) at ambient temperatures (T(a)) ranging from 27 degrees C to -5 degrees C. The expression of avUCP gene and mitochondrial bioenergetics were also determined in gastrocnemius muscle. Results showed that muscle NST capacity depends on the T(a) at which ducklings were acclimated, i.e. the lower the rearing temperature, the higher the capacity for NST. This increased metabolic heat production occurred in parallel with an upregulation of avUCP, which was not associated with a change in mitochondrial membrane conductance. The intensity of mitochondrial oxidative phosphorylation also increased in proportion with the harshness of cold, while the efficiency of ATP generation was equally effective in all three acclimation temperatures. In the absence of mitochondrial uncoupling, these data indicate a clear link between avUCP expression and the capacity of ducklings to adjust their muscular aerobic activity to cold exposure. PMID- 20581278 TI - Hysteresis in the production of force by larval Dipteran muscle. AB - We describe neuromuscular hysteresis - the dependence of muscle force on recent motoneuron activity - in the body wall muscles of larval Sarcophaga bullata and Drosophila melanogaster. In semi-intact preparations, isometric force produced by a train of nerve impulses at a constant rate was significantly less than that produced by the same train of stimuli with a brief (200 ms) high-frequency burst of impulses interspersed. Elevated force did not decay back to predicted values after the burst but instead remained high throughout the duration of the stimulus train. The increased force was not due to a change in excitatory junction potentials (EJPs); EJP voltage and time course before and after the high frequency burst were not statistically different. Single muscle and semi-intact preparations exhibited hysteresis similarly, suggesting that connective tissues of the origin or insertion are not crucial to the mechanism of hysteresis. Hysteresis was greatest at low motoneuron rates - yielding a approximately 100% increase over predicted values based on constant-rate stimulation alone - and decreased as impulse rate increased. We modulated motoneuron frequency rhythmically across rates and cycle periods similar to those observed during kinematic analysis of larval crawling. Positive force hysteresis was also evident within these more physiological activation parameters. PMID- 20581279 TI - Object preference by walking fruit flies, Drosophila melanogaster, is mediated by vision and graviperception. AB - Walking fruit flies, Drosophila melanogaster, use visual information to orient towards salient objects in their environment, presumably as a search strategy for finding food, shelter or other resources. Less is known, however, about the role of vision or other sensory modalities such as mechanoreception in the evaluation of objects once they have been reached. To study the role of vision and mechanoreception in exploration behavior, we developed a large arena in which we could track individual fruit flies as they walked through either simple or more topologically complex landscapes. When exploring a simple, flat environment lacking three-dimensional objects, flies used visual cues from the distant background to stabilize their walking trajectories. When exploring an arena containing an array of cones, differing in geometry, flies actively oriented towards, climbed onto, and explored the objects, spending most of their time on the tallest, steepest object. A fly's behavioral response to the geometry of an object depended upon the intrinsic properties of each object and not a relative assessment to other nearby objects. Furthermore, the preference was not due to a greater attraction towards tall, steep objects, but rather a change in locomotor behavior once a fly reached and explored the surface. Specifically, flies are much more likely to stop walking for long periods when they are perched on tall, steep objects. Both the vision system and the antennal chordotonal organs (Johnston's organs) provide sufficient information about the geometry of an object to elicit the observed change in locomotor behavior. Only when both these sensory systems were impaired did flies not show the behavioral preference for the tall, steep objects. PMID- 20581280 TI - Neuromuscular control of wingbeat kinematics in Anna's hummingbirds (Calypte anna). AB - Hummingbirds can maintain the highest wingbeat frequencies of any flying vertebrate - a feat accomplished by the large pectoral muscles that power the wing strokes. An unusual feature of these muscles is that they are activated by one or a few spikes per cycle as revealed by electromyogram recordings (EMGs). The relatively simple nature of this activation pattern provides an opportunity to understand how motor units are recruited to modulate limb kinematics. Hummingbirds made to fly in low-density air responded by moderately increasing wingbeat frequency and substantially increasing the wing stroke amplitude as compared with flight in normal air. There was little change in the number of spikes per EMG burst in the pectoralis major muscle between flight in normal and low-density heliox (mean=1.4 spikes cycle(-1)). However the spike amplitude, which we take to be an indication of the number of active motor units, increased in concert with the wing stroke amplitude, 1.7 times the value in air. We also challenged the hummingbirds using transient load lifting to elicit maximum burst performance. During maximum load lifting, both wing stroke amplitude and wingbeat frequency increased substantially above those values during hovering flight. The number of spikes per EMG burst increased to a mean of 3.3 per cycle, and the maximum spike amplitude increased to approximately 1.6 times those values during flight in heliox. These results suggest that hummingbirds recruit additional motor units (spatial recruitment) to regulate wing stroke amplitude but that temporal recruitment is also required to maintain maximum stroke amplitude at the highest wingbeat frequencies. PMID- 20581281 TI - Effects of flight speed upon muscle activity in hummingbirds. AB - Hummingbirds have the smallest body size and highest wingbeat frequencies of all flying vertebrates, so they represent one endpoint for evaluating the effects of body size on sustained muscle function and flight performance. Other bird species vary neuromuscular recruitment and contractile behavior to accomplish flight over a wide range of speeds, typically exhibiting a U-shaped curve with maxima at the slowest and fastest flight speeds. To test whether the high wingbeat frequencies and aerodynamically active upstroke of hummingbirds lead to different patterns, we flew rufous hummingbirds (Selasphorus rufus, 3 g body mass, 42 Hz wingbeat frequency) in a variable-speed wind tunnel (0-10 m s(-1)). We measured neuromuscular activity in the pectoralis (PECT) and supracoracoideus (SUPRA) muscles using electromyography (EMG, N=4 birds), and we measured changes in PECT length using sonomicrometry (N=1). Differing markedly from the pattern in other birds, PECT deactivation occurred before the start of downstroke and the SUPRA was deactivated before the start of upstroke. The relative amplitude of EMG signal in the PECT and SUPRA varied according to a U-shaped curve with flight speed; additionally, the onset of SUPRA activity became relatively later in the wingbeat at intermediate flight speeds (4 and 6 m s(-1)). Variation in the relative amplitude of EMG was comparable with that observed in other birds but the timing of muscle activity was different. These data indicate the high wingbeat frequency of hummingbirds limits the time available for flight muscle relaxation before the next half stroke of a wingbeat. Unlike in a previous study that reported single-twitch EMG signals in the PECT of hovering hummingbirds, across all flight speeds we observed 2.9+/-0.8 spikes per contraction in the PECT and 3.8+/-0.8 spikes per contraction in the SUPRA. Muscle strain in the PECT was 10.8+/-0.5%, the lowest reported for a flying bird, and average strain rate was 7.4+/-0.2 muscle lengths s(-1). Among species of birds, PECT strain scales proportional to body mass to the 0.2 power (infinityM(b)(0.2)) using species data and infinityM(b)(0.3) using independent contrasts. This positive scaling is probably a physiological response to an adverse scaling of mass-specific power available for flight. PMID- 20581283 TI - Sugar preferences and digestive efficiency of the village weaver: a generalist avian pollinator of African plants. AB - Recent research has shown that nectar properties of flowers pollinated by generalist avian nectarivores differ markedly from those of flowers pollinated by specialist avian nectarivores. In particular, flowers pollinated by generalist avian nectarivores tend to have very dilute nectar dominated by hexose sugars. To establish whether pollinator-mediated selection can explain these traits, we tested nectar sugar preferences and digestive capabilities of the village weaver (Ploceus cucullatus), a common generalist passerine nectarivore in South Africa. When offered pairwise choices of equicaloric hexose and sucrose solutions, village weavers preferred hexose solutions at 5% and 10% sucrose equivalents (SE) but did not show significant preference for either type of sugar when higher concentrations were offered (15%, 20% and 25% SE). Birds were less efficient at absorbing sucrose than hexose sugars, as revealed by high-performance liquid chromatography (HPLC) analysis of excreta sugar content. This was true at both concentrations tested (8.22% and 25%), although apparent sucrose assimilation rates were still relatively high (89.6+/-2.9% at low concentrations and 93.6+/ 1.7% at high concentrations). Transit times indicated that sucrose also passes through the digestive tract faster than hexose sugars, particularly when consumed at high concentrations. This may limit the rate at which sucrose can be hydrolyzed before absorption. These results indicate that hexose preferences in generalist avian nectarivores may help explain the low sucrose content in flowers pollinated by these birds. Moreover, the preference for hexose sugars in weavers was most evident at the low concentrations (ca. 9% sugar by mass) that are typical of nectar in flowers pollinated by generalist avian nectarivores. PMID- 20581282 TI - Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups. AB - Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences. PMID- 20581284 TI - Adrenergic control of swimbladder deflation in the zebrafish (Danio rerio). AB - Many teleosts actively regulate buoyancy by adjusting gas volume in the swimbladder. In physostomous fishes such as the zebrafish, a connection is maintained between the swimbladder and the oesophagus via the pneumatic duct for the inflation and deflation of this organ. Here we investigated the role of adrenergic stimulation of swimbladder wall musculature in deflation of the swimbladder. Noradrenaline (NA), the sympathetic neurotransmitter (dosage 10(-6) to 10(-5) mol l(-1)), doubled the force of smooth muscle contraction in isolated tissue rings from the anterior chamber, caused a doubling of pressure in this chamber in situ, and evoked gas expulsion through the pneumatic duct, deflating the swimbladder to approximately 85% of the pre-NA volume. These effects were mediated by beta-adrenergic receptors, representing a novel role for these receptors in vertebrates. No effects of adrenergic stimulation were detected in the posterior chamber. In a detailed examination of the musculature and innervation of the swimbladder to determine the anatomical substrate for these functional results, we found that the anterior chamber contained an extensive ventral band of smooth muscle with fibres organized into putative motor units, richly innervated by tyrosine hydroxylase-positive axons. Additionally, a novel arrangement of folds in the lumenal connective tissue in the wall of the anterior chamber was described that may permit small changes in muscle length to cause large changes in effective wall distensibility and hence chamber volume. Taken together, these data strongly suggest that deflation of the zebrafish swimbladder occurs primarily by beta-adrenergically mediated contraction of smooth muscle in the anterior chamber and is under the control of the sympathetic limb of the autonomic nervous system. PMID- 20581285 TI - Genetics of fighting ability in cattle using data from the traditional battle contest of the Valdostana breed. AB - The tendency to fight is a well-known behavior in Valdostana cattle, and non cruel traditional contests are organized yearly by farmers to identify the most dominant cow. Cow battles consist of elimination matches that have important economic implications for both tourism and farmers. The aims of this study are 1) to validate a scoring system to express fighting ability, and 2) to carry out a genetic analysis for this trait using different data sets and models. A data set accounting for 16,509 fighting records of 5,981 cows relevant to contests over 6 yr was retained after editing (data set 1). Data on placements were used to compute a placement score accounting for wins, tournament size, and difficulty, and differentiating the 20 preliminary battles each year from the final match. A second data set was created using only the individual best yearly placement scores, that is, deleting repeats with a smaller placement score for the same animal within each year (data set 2; n = 10,367 records, corresponding to a single datum per year per cow). Compared with the placement or position of each cow, the placement score proved to be less skewed (-1.45 for placement position and 1.25 for placement score, respectively) and exhibited better coefficients for the probability of a normal distribution. An animal model REML method analysis (accounting for 13,456 animals in the pedigree) was carried out, with consideration given to different combinations of fixed and random nongenetic factors other than the random animal and permanent environmental effects. Results indicated that random factors other than additive genetic and permanent environment effects did not improve the model fit; therefore, it was not useful to take them into account. Heritability estimates obtained with the model showing the best fit were 0.078 (data set 1) and 0.098 (data set 2). Results of this study indicate that selection for fighting ability in Valdostana cattle using data on battle performance is possible. PMID- 20581286 TI - Detection of a quantitative trait locus for ham weight with polar overdominance near the ortholog of the callipyge locus in an experimental pig F2 population. AB - The distal part of SSC7, which contains the ortholog to the ovine region encompassing the callipyge locus, was analyzed in a Pietrain F(2) resource population comprising more than 2,700 offspring. The aim of the study was to map QTL affecting carcass traits comparable with the callipyge phenotype in sheep. We applied an interval mapping approach using 14 microsatellite markers and detected 3 QTL with small effects. The first QTL affects fat thickness on the middle of the back, with no detectable impact on fat sizes at other places on the back, whereas the second QTL affects side fat thickness. The third QTL influences the ham weight and shows a clear parent-of-origin-dependent effect in the form of maternal polar overdominance. It is not located at the position of the imprinting cluster including the callipyge locus, but 7 cM proximal. PMID- 20581287 TI - Dietary nitrogen reduction enhances urea transport across goat rumen epithelium. AB - Ruminants are very capable of adapting their N homeostasis to a reduced dietary N intake. However, the limits of this physiological adaptation are still unknown. The aim of the present study was to determine the quantity of dietary N intake at which the needs of the animal are still satisfied. A study was performed in young White Saanen goats under conditions of dietary N reduction. Different semisynthetic diets with 19 to 7% CP were fed. Urea transport rates across the rumen epithelium from the blood into the ruminal fluid were quantified by Ussing chamber experiments. Reduced N intake increased urea transport rates across the mucosa, which could be inhibited by phloretin. The role of parietal urease in driving urea transfer across the epithelium was negligible because its activity was inhibited by antibiotics during in vitro incubations of the epithelium. Concentrations of ammonia in the ruminal fluid were decreased by reducing dietary N intake, accompanied by diminished urease activity at the smallest dietary N intake. Over the range of plasma urea concentrations observed in the different feeding groups, salivary urea concentrations were 73% of plasma urea concentrations. By plotting plasma urea concentrations against serosal to mucosal urea flux rates, a threshold at 1.75 mmol of urea/L of plasma could be assessed, below which urea flux was strongly increased. This indicates that rumen urea transfer could be stimulated by decreased plasma urea concentrations via unknown mechanisms. The physiological relevance of this adaptation of the rumen epithelium is that it is considered a central mechanism in the N homeostasis of growing goats under reduced N intake. PMID- 20581288 TI - Evaluation of tropically adapted straightbred and crossbred beef cattle: heifer age and size at first conception and characteristics of their first calves. AB - The objectives of this work were to estimate genetic effects for age and size at estimated time of first conception, and temperament in straightbred and crossbred heifers (n = 554) produced from Romosinuano, Brahman, and Angus cattle, and to evaluate first-parturition performance of heifers, including calf birth weight, occurrence of calving difficulty, occurrence of poor vigor in their newborn calves, and calf mortality. At approximately 7 mo of age, weaned heifers were pastured with Mashona or Tuli bulls until confirmed pregnant. Body weight, hip height, exit velocity (m/s), and chute temperament score (1 = calm, no movement; 5 = continuous movement, struggling) were recorded at 28-d intervals until heifers averaged 19 mo of age. Age at first conception was estimated as age at calving minus 285 d. Regression analyses were used to estimate BW and hip height at age of first conception. Brahman heifers were older, heavier, and had greater hip height than other straightbred groups (P < 0.05) and most crossbred groups. Brahman and reciprocal Brahman-Angus heifers had greater (P < 0.05) exit velocity than Romosinuano and Angus heifers. Brahman sire and dam breed chute temperament scores were greater (P < 0.05) than those of all other breed groups. Estimates of heterosis for age at first conception were -53.7 +/- 9.5 (-11%), -56 +/- 10.1 ( 11%), and -92.9 +/- 11 d (-18%) for Romosinuano-Brahman, Romosinuano-Angus, and Brahman-Angus, respectively (P < 0.01). Heterosis was detected (P < 0.04) for Romosinuano-Brahman for BW (12 +/- 4.3 kg, 3.7%) and hip height (1.3 +/- 0.6 cm, 1%) at first conception. Maternal heterosis for calf birth weight was 3.6 +/- 0.5 (12%) and 2.4 +/- 0.6 kg (8.6%) for Romosinuano-Angus and Brahman-Angus. In Romosinuano-Brahman and Brahman-Angus, heterosis for exit velocity was 0.23 +/- 0.09 (10%) and 0.5 +/- 0.1 m/s (21%). The direct breed effect of Romosinuano was to reduce age (-58.2 +/- 18.9 d), BW (-57.6 +/- 10.5 kg), and hip height (-2.6 +/ 1.1 cm) at the time of first conception (P < 0.01), and the direct Brahman effects (P < 0.001) were large and numerically positive for these traits (169.8 +/- 20.8 d, 93.3 +/- 11.6 kg, and 14 +/- 1.2 cm). Use of Romosinuano in crossbreeding programs with Brahman may be useful for decreasing the age at first conception. The larger birth weights of calves born to Romosinuano-Angus cross heifers would not be desirable in southern cow-calf operations. PMID- 20581289 TI - Voluntary intake and digestibility of teff hay fed to horses. AB - The objective of this study was to evaluate nutrient composition, voluntary DMI, and apparent DM digestibility of teff hay cut at 3 different stages of maturity to evaluate its potential as a preserved forage for horses. Six mature Quarter Horse mares (12 +/- 3 yr; 553 +/- 39 kg of BW) were used in a replicated balanced Latin square design with 3 periods and 3 maturities of teff hay. Eragrostis tef ('Tiffany' teff) was planted in May and harvested at the boot, early-heading, or late-heading stage of maturity through the summer. Horses were acclimated to a mixture of maturities of teff hay for 8 d before the beginning of the study. After this acclimation period, each period consisted of a 9-d voluntary DMI phase, followed by a 3-d DM digestibility phase. The percentages of nonstructural carbohydrates (NSC) increased from 5.4% in the boot stage to 8.4% in the late heading stage, whereas concentrations of CP, K, Fe, and Mn decreased. The Ca:P ratio was 2.0 +/- 0.3 for all maturities. Horses had less DMI of late-heading teff hay (1.5% BW) than teff hay of other maturities (1.8% BW; P < 0.05), indicating a preference for the earlier maturities. The intake and nutrient composition of the boot and early-heading maturities was sufficient to meet 90 to 97% of the average DE of the horses and most other nutrient requirements. Digestibility decreased from boot to late-heading teff hay for DM, CP, ADF, and NDF (P < 0.05). Digestibility increased from boot to early-heading to late heading hay for nonfiber carbohydrates and water-soluble carbohydrates (P < 0.05). For all maturities of teff hay, the NSC intake was below 10% of the total intake. In conclusion, the low NSC and DE of teff hay grown in central Pennsylvania under the conditions in this study make it an appropriate forage source for obese horses and those at risk for laminitis or other metabolic disorders. PMID- 20581290 TI - Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host. AB - Cryptococcus neoformans is an environmental fungus and an opportunistic human pathogen. Previous studies have demonstrated major alterations in its transcriptional profile as this microorganism enters the hostile environment of the human host. To assess the role of chromatin remodeling in host-induced transcriptional responses, we identified the C. neoformans Gcn5 histone acetyltransferase and demonstrated its function by complementation studies of Saccharomyces cerevisiae. The C. neoformans gcn5Delta mutant strain has defects in high-temperature growth and capsule attachment to the cell surface, in addition to increased sensitivity to FK506 and oxidative stress. Treatment of wild-type cells with the histone acetyltransferase inhibitor garcinol mimics cellular effects of the gcn5Delta mutation. Gcn5 regulates the expression of many genes that are important in responding to the specific environmental conditions encountered by C. neoformans inside the host. Accordingly, the gcn5Delta mutant is avirulent in animal models of cryptococcosis. Our study demonstrates the importance of chromatin remodeling by the conserved histone acetyltransferase Gcn5 in regulating the expression of specific genes that allow C. neoformans to respond appropriately to the human host. PMID- 20581291 TI - C terminus of Nce102 determines the structure and function of microdomains in the Saccharomyces cerevisiae plasma membrane. AB - The plasma membrane of the yeast Saccharomyces cerevisiae contains stably distributed lateral domains of specific composition and structure, termed MCC (membrane compartment of arginine permease Can1). Accumulation of Can1 and other specific proton symporters within MCC is known to regulate the turnover of these transporters and is controlled by the presence of another MCC protein, Nce102. We show that in an NCE102 deletion strain the function of Nce102 in directing the specific permeases into MCC can be complemented by overexpression of the NCE102 close homolog FHN1 (the previously uncharacterized YGR131W) as well as by distant Schizosaccharomyces pombe homolog fhn1 (SPBC1685.13). We conclude that this mechanism of plasma membrane organization is conserved through the phylum Ascomycota. We used a hemagglutinin (HA)/Suc2/His4C reporter to determine the membrane topology of Nce102. In contrast to predictions, its N and C termini are oriented toward the cytosol. Deletion of the C terminus or even of its last 6 amino acids does not disturb protein trafficking, but it seriously affects the formation of MCC. We show that the C-terminal part of the Nce102 protein is necessary for localization of both Nce102 itself and Can1 to MCC and also for the formation of furrow-like membrane invaginations, the characteristic ultrastructural feature of MCC domains. PMID- 20581292 TI - Cellular and molecular remodeling of the endocytic pathway during differentiation of Trypanosoma brucei bloodstream forms. AB - During the course of mammalian infection, African trypanosomes undergo extensive cellular differentiation, as actively dividing long slender (SL) forms progressively transform into intermediate (I) forms and finally quiescent G(1)/G(0)-locked short stumpy (ST) forms. ST forms maintain adaptations compatible with their survival in the mammalian bloodstream, such as high endocytic activity, but they already show preadaptations to the insect midgut conditions. The nutritional requirements of ST forms must differ from those of SL forms because the ST forms stop multiplying. We report that the uptake of several ligands was reduced in ST forms compared with that in SL forms. In particular, the haptoglobin-hemoglobin (Hp-Hb) complex was no longer taken up due to dramatic downregulation of its cognate receptor, TbHpHbR. As this receptor also allows uptake of trypanolytic particles from human serum, ST forms were resistant to trypanolysis by human serum lipoproteins. These observations allowed both flow cytometry analysis of SL-to-ST differentiation and the generation of homogeneous ST populations after positive selection upon exposure to trypanolytic particles. In addition, we observed that in ST forms the lysosome relocates anterior to the nucleus. Altogether, we identified novel morphological and molecular features that characterize SL-to-ST differentiation. PMID- 20581293 TI - The pre-mRNA splicing machinery of trypanosomes: complex or simplified? AB - Trypanosomatids are early-diverged, protistan parasites of which Trypanosoma brucei, Trypanosoma cruzi, and several species of Leishmania cause severe, often lethal diseases in humans. To better combat these parasites, their molecular biology has been a research focus for more than 3 decades, and the discovery of spliced leader (SL) trans splicing in T. brucei established a key difference between parasites and hosts. In SL trans splicing, the capped 5'-terminal region of the small nuclear SL RNA is fused onto the 5' end of each mRNA. This process, in conjunction with polyadenylation, generates individual mRNAs from polycistronic precursors and creates functional mRNA by providing the cap structure. The reaction is a two-step transesterification process analogous to intron removal by cis splicing which, in trypanosomatids, is confined to very few pre-mRNAs. Both types of pre-mRNA splicing are carried out by the spliceosome, consisting of five U-rich small nuclear RNAs (U snRNAs) and, in humans, up to approximately 170 different proteins. While trypanosomatids possess a full set of spliceosomal U snRNAs, only a few splicing factors were identified by standard genome annotation because trypanosomatid amino acid sequences are among the most divergent in the eukaryotic kingdom. This review focuses on recent progress made in the characterization of the splicing factor repertoire in T. brucei, achieved by tandem affinity purification of splicing complexes, by systematic analysis of proteins containing RNA recognition motifs, and by mining the genome database. In addition, recent findings about functional differences between trypanosome and human pre-mRNA splicing factors are discussed. PMID- 20581294 TI - The Candida albicans ESCRT pathway makes Rim101-dependent and -independent contributions to pathogenesis. AB - Candida albicans is an opportunistic pathogen that colonizes diverse mucosal niches with distinct environmental characteristics. To adapt to these different sites, C. albicans must activate and attenuate a variety of signal transduction pathways. A mechanism of signal attenuation is through receptor endocytosis and subsequent vacuolar degradation, which requires the endosomal sorting complex required for transport (ESCRT) pathway. This pathway comprises several polyprotein complexes (ESCRT-0, -I, -II, -III, and -DS) that are sequentially recruited to the endosomal membrane. The ESCRT pathway also activates the Rim101 transcription factor, which governs expression of genes required for virulence. Here, we tested the hypothesis that the ESCRT pathway plays a Rim101-independent role(s) in pathogenesis. We generated deletion mutants in each ESCRT complex and determined that ESCRT-I, -II, and -III are required for Rim101 activation but that ESCRT-0 and ESCRT-DS are not. We found that the ESCRT-0 member Vps27 and ESCRT-DS components are required to promote epithelial cell damage and, using a murine model of oral candidiasis, found that the vps27Delta/Delta mutant had a decreased fungal burden compared to that of the wild type. We found that a high dose inoculum can compensate for fungal burden defects but that mice colonized with the vps27Delta/Delta strain exhibit less morbidity than do mice infected with the wild-type strain. These results demonstrate that the ESCRT pathway has Rim101-independent functions for C. albicans virulence. PMID- 20581295 TI - Uga3 and Uga35/Dal81 transcription factors regulate UGA4 transcription in response to gamma-aminobutyric acid and leucine. AB - The Saccharomyces cerevisiae UGA4 gene encodes a permease capable of importing gamma-aminobutyric acid (GABA) and delta-aminolevulinic acid (ALA) into the cell. GABA-dependent induction of this permease requires at least two positive-acting proteins, the specific factor Uga3 and the pleiotropic factor Uga35/Dal81. UGA4 is subjected to a very complex regulation, and its induction is affected by the presence of extracellular amino acids; this effect is mediated by the plasma membrane amino acid sensor SPS. Our results show that leucine affects UGA4 induction and that the SPS sensor and the downstream effectors Stp1 and Stp2 participate in this regulation. Moreover, we found that the Uga3 and Uga35/Dal81 transcription factors bind to the UGA4 promoter in a GABA-dependent manner and that this binding is impaired by the presence of leucine. We also found that the Leu3 transcription factor negatively regulates UGA4 transcription, although this seems to be through an indirect mechanism. PMID- 20581299 TI - Specific targets in sarcoma and developmental therapeutics. AB - Connective tissue tumors comprise a rich array of subtypes, many of which possess strong pathognomonic phenotypes and genotypes of therapeutic significance. This article describes recent applications of targeted and nontargeted therapeutic agents in connective tissue tumors that illustrate important themes in drug development. Targeted therapy has exploited the paradigms of oncogene and lineage addiction. In other cases, potential targets are more difficult to classify, such as the role of the insulin-like growth factor 1 pathway in Ewing's sarcoma. Understanding why these pathways seem critical in some cancers, and in some individuals but not others, is important in identifying novel therapeutic opportunities in an age of personalized medicine. PMID- 20581298 TI - Soft tissue sarcoma. PMID- 20581296 TI - Downregulation of an Entamoeba histolytica rhomboid protease reveals roles in regulating parasite adhesion and phagocytosis. AB - Entamoeba histolytica is a deep-branching eukaryotic pathogen. Rhomboid proteases are intramembrane serine proteases, which cleave transmembrane proteins in, or in close proximity to, their transmembrane domain. We have previously shown that E. histolytica contains a single functional rhomboid protease (EhROM1) and has unique substrate specificity. EhROM1 is present on the trophozoite surface and relocalizes to internal vesicles during erythrophagocytosis and to the base of the cap during surface receptor capping. In order to further examine the biological function of EhROM1 we downregulated EhROM1 expression by >95% by utilizing the epigenetic silencing mechanism of the G3 parasite strain. Despite the observation that EhROM1 relocalized to the cap during surface receptor capping, EhROM1 knockdown [ROM(KD)] parasites had no gross changes in cap formation or complement resistance. However, ROM(KD) parasites demonstrated decreased host cell adhesion, a result recapitulated by treatment of wild-type parasites with DCI, a serine protease inhibitor with activity against rhomboid proteases. The reduced adhesion phenotype of ROM(KD) parasites was noted exclusively with healthy cells, and not with apoptotic cells. Additionally, ROM(KD) parasites had decreased phagocytic ability with reduced ingestion of healthy cells, apoptotic cells, and rice starch. Decreased phagocytic ability is thus independent of the reduced adhesion phenotype, since phagocytosis of apoptotic cells was reduced despite normal adhesion levels. The defect in host cell adhesion was not explained by altered expression or localization of the heavy subunit of the Gal/GalNAc surface lectin. These results suggest no significant role of EhROM1 in complement resistance but unexpected roles in parasite adhesion and phagocytosis. PMID- 20581300 TI - Bone cancer. PMID- 20581301 TI - Experimental therapies and clinical trials in bone sarcoma. AB - Sarcomas originating in the bone represent a challenge for physicians and patients. Because they constitute only 0.2% of all adult malignancies and 6% of pediatric malignancies, resources for studying this disease are often limited. Nonetheless, significant advancements have been made in the treatment of this disease, and there are ongoing efforts toward improvement. This article discusses recently completed and currently enrolling clinical trials for the 3 most common bone sarcomas: osteosarcoma, Ewing's sarcoma family tumors, and chondrosarcoma. PMID- 20581302 TI - Pelvic bone sarcomas: controversies and treatment options. AB - Treatment of pelvic bone sarcomas remains one of the most challenging areas of orthopedic oncology for all members of the disease management team. Although considerable advances have been made in all aspects of sarcoma treatment, the prognosis for patients with primary sarcomas of the pelvis continues to be guarded, and therefore, much controversy exists regarding optimal surgical management, radiation therapy, and systemic therapy. This article summarizes the current treatment paradigms for the 3 most common bone sarcomas (osteosarcoma, Ewing's sarcoma, and chondrosarcoma), highlighting the unresolved issues in their management as they pertain to the pelvis. PMID- 20581303 TI - RAV-Like1 maintains brassinosteroid homeostasis via the coordinated activation of BRI1 and biosynthetic genes in rice. AB - Temporal and spatial variation in the levels of and sensitivity to hormones are essential for the development of higher organisms. Traditionally, end-product feedback regulation has been considered as the key mechanism for the achievement of cellular homeostasis. Brassinosteroids (BRs) are plant steroid hormones that are perceived by the cell surface receptor kinase Brassinosteroid Insensitive1. Binding of these hormones to the receptor activates BR signaling and eventually suppresses BR synthesis. This report shows that RAVL1 regulates the expression of the BR receptor. Furthermore, RAVL1 is also required for the expression of the BR biosynthetic genes D2, D11, and BRD1 that are subject to BR negative feedback. Activation by RAVL1 was coordinated via E-box cis-elements in the promoters of the receptor and biosynthetic genes. Also, RAVL1 is necessary for the response of these genes to changes in cellular BR homeostasis. Genetic evidence is presented to strengthen the observation that the primary action of RAVL1 mediates the expression of genes involved in BR signaling and biosynthesis. This study thus describes a regulatory circuit modulating the homeostasis of BR in which RAVL1 ensures the basal activity of both the signaling and the biosynthetic pathways. PMID- 20581304 TI - Class XI myosins are required for development, cell expansion, and F-Actin organization in Arabidopsis. AB - The actomyosin system is conserved throughout eukaryotes. Although F-actin is essential for cell growth and plant development, roles of the associated myosins are poorly understood. Using multiple gene knockouts in Arabidopsis thaliana, we investigated functional profiles of five class XI myosins, XI-K, XI-1, XI-2, XI B, and XI-I. Plants lacking three myosins XI showed stunted growth and delayed flowering, whereas elimination of four myosins further exacerbated these defects. Loss of myosins led to decreased leaf cell expansion, with the most severe defects observed in the larger leaf cells. Root hair length in myosin-deficient plants was reduced approximately 10-fold, with quadruple knockouts showing morphological abnormalities. It was also found that trafficking of Golgi and peroxisomes was entirely myosin dependent. Surprisingly, myosins were required for proper organization of F-actin and the associated endoplasmic reticulum networks, revealing a novel, architectural function of the class XI myosins. These results establish critical roles of myosin-driven transport and F-actin organization during polarized and diffuse cell growth and indicate that myosins are key factors in plant growth and development. PMID- 20581305 TI - VERDANDI is a direct target of the MADS domain ovule identity complex and affects embryo sac differentiation in Arabidopsis. AB - In Arabidopsis thaliana, the three MADS box genes SEEDSTICK (STK), SHATTERPROOF1 (SHP1), and SHP2 redundantly regulate ovule development. Protein interaction studies have shown that a multimeric complex composed of the ovule identity proteins together with the SEPALLATA MADS domain proteins is necessary to determine ovule identity. Despite the extensive knowledge that has become available about these MADS domain transcription factors, little is known regarding the genes that they regulate. Here, we show that STK, SHP1, and SHP2 redundantly regulate VERDANDI (VDD), a putative transcription factor that belongs to the plant-specific B3 superfamily. The vdd mutant shows defects during the fertilization process resulting in semisterility. Analysis of the vdd mutant female gametophytes indicates that antipodal and synergid cell identity and/or differentiation are affected. Our results provide insights into the pathways regulated by the ovule identity factors and the role of the downstream target gene VDD in female gametophyte development. PMID- 20581306 TI - Sweet and sour: a scientific and legal look at herbicide-tolerant sugar beet. PMID- 20581307 TI - Megabase level sequencing reveals contrasted organization and evolution patterns of the wheat gene and transposable element spaces. AB - To improve our understanding of the organization and evolution of the wheat (Triticum aestivum) genome, we sequenced and annotated 13-Mb contigs (18.2 Mb) originating from different regions of its largest chromosome, 3B (1 Gb), and produced a 2x chromosome survey by shotgun Illumina/Solexa sequencing. All regions carried genes irrespective of their chromosomal location. However, gene distribution was not random, with 75% of them clustered into small islands containing three genes on average. A twofold increase of gene density was observed toward the telomeres likely due to high tandem and interchromosomal duplication events. A total of 3222 transposable elements were identified, including 800 new families. Most of them are complete but showed a highly nested structure spread over distances as large as 200 kb. A succession of amplification waves involving different transposable element families led to contrasted sequence compositions between the proximal and distal regions. Finally, with an estimate of 50,000 genes per diploid genome, our data suggest that wheat may have a higher gene number than other cereals. Indeed, comparisons with rice (Oryza sativa) and Brachypodium revealed that a high number of additional noncollinear genes are interspersed within a highly conserved ancestral grass gene backbone, supporting the idea of an accelerated evolution in the Triticeae lineages. PMID- 20581309 TI - Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes" (AML-MRC). AB - The World Health Organization classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetics, data on patients' history, and multilineage dysplasia (MLD). The category "AML with myelodysplastic syndrome (MDS)-related changes" (AML-MRC) is separated from "AML not otherwise specified" (AML-NOS) by presence of MLD, MDS-related cytogenetics, or history of MDS or MDS/myeloproliferative neoplasm (MPN). We analyzed 408 adult patients categorized as AML-MRC or AML-NOS. Three-year event-free survival (EFS; median, 13.8 vs 16.0 months) and 3-year overall survival (OS; 45.8% vs 53.9%) did not differ significantly between patients with MLD versus without. However, MLD correlated with preexisting MDS (P < .001) and MDS-related cytogenetics (P = .035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n = 90) had less frequently FLT3 internal tandem duplication (P = .032) and lower median age than AML-NOS (n = 232). Contrarily, patients with AML-NOS combined with AML-MLD-sole (n = 323) had better 3-year EFS (16.9 vs 10.7 months; P = .005) and 3-year OS (55.8% vs 32.5%; P = .001) than patients with history of MDS or MDS/MPN or MDS-related cytogenetics (n = 85). Gene expression analysis showed distinct clusters for AML MLD-sole combined with AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD alone showed no independent clinical effect, whereas cytogenetics and MDS history were prognostically relevant. PMID- 20581308 TI - Genome-wide distribution of transposed Dissociation elements in maize. AB - The maize (Zea mays) transposable element Dissociation (Ds) was mobilized for large-scale genome mutagenesis and to study its endogenous biology. Starting from a single donor locus on chromosome 10, over 1500 elements were distributed throughout the genome and positioned on the maize physical map. Genetic strategies to enrich for both local and unlinked insertions were used to distribute Ds insertions. Global, regional, and local insertion site trends were examined. We show that Ds transposed to both linked and unlinked sites and displayed a nonuniform distribution on the genetic map around the donor r1-sc:m3 locus. Comparison of Ds and Mutator insertions reveals distinct target preferences, which provide functional complementarity of the two elements for gene tagging in maize. In particular, Ds displays a stronger preference for insertions within exons and introns, whereas Mutator insertions are more enriched in promoters and 5'-untranslated regions. Ds has no strong target site consensus sequence, but we identified properties of the DNA molecule inherent to its local structure that may influence Ds target site selection. We discuss the utility of Ds for forward and reverse genetics in maize and provide evidence that genes within a 2- to 3-centimorgan region flanking Ds insertions will serve as optimal targets for regional mutagenesis. PMID- 20581310 TI - New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases. AB - A large number of alterations in genes encoding receptor tyrosine kinase (RTK), namely FLT3, c-KIT, platelet-derived growth factor (PDGF) receptors, fibroblast growth factor (FGF) receptors, and the anaplastic large cell lymphoma kinase (ALK), have been found in hematopoietic malignancies. They have drawn much attention after the development of tyrosine kinase inhibitors. RTK gene alterations include point mutations and gene fusions that result from chromosomal rearrangements. In both cases, they activate the kinase domain in the absence of ligand, producing a permanent signal for cell proliferation. Recently, this simple model has been refined. First, by contrast to wild-type RTK, many mutated RTK do not seem to signal from the plasma membrane, but from various locations inside the cell. Second, their signal transduction properties are altered: the pathways that are crucial for cell transformation, such as signal transducer and activator of transcription (STAT) factors, do not necessarily contribute to the physiologic functions of these receptors. Finally, different mechanisms prevent the termination of the signal, which normally occurs through receptor ubiquitination and degradation. Several mutations inactivating CBL, a key RTK E3 ubiquitin ligase, have been recently described. In this review, we discuss the possible links among RTK trafficking, signaling, and degradation in leukemic cells. PMID- 20581311 TI - STAT3 controls myeloid progenitor growth during emergency granulopoiesis. AB - Granulocyte colony-stimulating factor (G-CSF) mediates "emergency" granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular signaling cascades that control demand driven neutrophil production. Using a murine model with conditional deletion of signal transducer and activator of transcription 3 (STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of STAT3 function in the emergency granulopoiesis response to G-CSF administration or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic progenitor cells and myeloid precursors refractory to the growth-promoting functions of G-CSF or L monocytogenes infection. STAT3 is necessary for accelerating granulocyte cell cycle progression and maturation in response to G-CSF. STAT3 directly controls G CSF-dependent expression of CCAAT-enhancer-binding protein beta (C/EBPbeta), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPbeta coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPalpha occupancy during demand-driven granulopoiesis. These results place STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF-responsive myeloid progenitor expansion. PMID- 20581312 TI - Assessment of disease severity and outcome in patients with systemic light-chain amyloidosis by the high-sensitivity troponin T assay. AB - Cardiac biomarkers provide prognostic information in light-chain amyloidosis (AL). Thus, a novel high-sensitivity cardiac troponin T (hs-TnT) assay may improve risk stratification. hs-TnT was assessed in 163 patients. Blood levels were higher with cardiac than renal or other organ involvement and were related to the severity of cardiac involvement. Increased sensitivity was not associated with survival benefit. Forty-seven patients died during follow-up (22.3 +/- 1.0 months). Nonsurvivors had higher hs-TnT than survivors. Outcome was worse if hs TnT more than or equal to 50 ng/L and best less than 3 ng/L. Survival of patients with hs-TnT 3 to 14 ng/L did not differ from patients with moderately increased hs-TnT (14-50 ng/L), but was worse if interventricular septum was more than or equal to 15 mm. Discrimination according to the Mayo staging system was only achieved by the use of the hs-TnT assay, but not by the fourth-generation troponin T assay. Multivariate analysis revealed hs-TnT, NT-proBNP, and left ventricular impairment as independent risk factors for survival. hs-TnT and NT proBNP predicted survival, even after exclusion of patients with impaired renal function. Plasma levels of the hs-TnT assay are associated with the clinical, morphologic, and functional severity of cardiac AL amyloidosis and could provide useful information for clinicians on cardiac involvement and outcome. PMID- 20581313 TI - Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. AB - Killer-cell immunoglobulin-like receptor (KIR) genes form a diverse, immunogenetic system. Group A and B KIR haplotypes have distinctive centromeric (Cen) and telomeric (Tel) gene-content motifs. Aiming to develop a donor selection strategy to improve transplant outcome, we compared the contribution of these motifs to the clinical benefit conferred by B haplotype donors. We KIR genotyped donors from 1409 unrelated transplants for acute myelogenous leukemia (AML; n = 1086) and acute lymphoblastic leukemia (ALL; n = 323). Donor KIR genotype influenced transplantation outcome for AML but not ALL. Compared with A haplotype motifs, centromeric and telomeric B motifs both contributed to relapse protection and improved survival, but Cen-B homozygosity had the strongest independent effect. With Cen-B/B homozygous donors the cumulative incidence of relapse was 15.4% compared with 36.5% for Cen-A/A donors (relative risk of relapse 0.34; 95% confidence interval 0.2-0.57; P < .001). Overall, significantly reduced relapse was achieved with donors having 2 or more B gene-content motifs (relative risk 0.64; 95% confidence interval 0.48-0.86; P = .003) for both HLA matched and mismatched transplants. KIR genotyping of several best HLA-matched potential unrelated donors should substantially increase the frequency of transplants by using grafts with favorable KIR gene content. Adopting this practice could result in superior disease-free survival for patients with AML. PMID- 20581315 TI - Editor's note. Providing nutrition support to individuals who have special nutrient needs. PMID- 20581314 TI - Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation. AB - Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells was crucial for generating normal number of iNKTs in the thymus, whereas both hematopoietic and parenchymal cells regulated iNKT cell numbers in the periphery, particularly in the liver. Specifically, dendritic cells contributed to peripheral iNKT cell numbers by up regulating Bcl-2 expression and promoting extrathymic iNKT cell ex-pansion and their homeostatic proliferation. Whether IL-15 affects functional maturation of iNKT cells was also examined. In IL-15Ralpha(-/-) mice, CD44(High)NK1.1(+) iNKT cells displayed decreased T-bet expression and in response to alpha galactosylceramide, had deficient interferon-gamma expression. Such defects could be reversed by exogenous IL-15 signals. Overall, these studies identify stage specific functions of IL-15, which are determined by the tissue microenvironment and elucidate the importance of IL-15 in functional maturation. PMID- 20581316 TI - Nutrition and pancreaticoduodenectomy. AB - Pancreaticoduodenectomy (Whipple) is the surgical procedure of choice for curative resection of pancreatic head, periampullary, and distal bile duct cancers. This procedure involves removal of the pancreatic head, duodenum, distal common bile duct, and sometimes the pylorus and gastric antrum. The 2 most common complications are pancreatic fistula and delayed gastric emptying. Preoperative nutrition status has been shown to influence surgical outcomes. This technically demanding operation involves an extensive surgical resection and alters digestive processes, which can influence nutrition long term. This review article identifies the surgical and nutrition consequences associated with pancreaticoduodenectomy. PMID- 20581317 TI - Role of esophageal stents in the nutrition support of patients with esophageal malignancy. AB - Endoluminal stents are commonly used for palliative treatment of dysphagia in patients with advanced esophageal malignancies. The most frequently used esophageal stents are self-expanding metal stents. Removable self-expanding plastic stents have recently been used in the management of esophageal cancer patients treated with curative intent. Esophageal stents effectively alleviate dysphagia in most patients, and stent placement is associated with a low rate of complications. This article reviews the use of self-expanding esophageal stents in patients with esophageal cancer. Nutrition considerations following stent placement are addressed. PMID- 20581318 TI - Nutrition considerations surrounding restorative proctocolectomy. AB - Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with ulcerative colitis and familial polyposis coli syndromes. Pouch construction uses the distal 30-40 cm of ileum, and there exists a potential for postoperative nutrition consequences. These include vitamin B(12) deficiency, iron deficiency, bile acid malabsorption, and abnormalities of trace elements, fluids, and electrolytes. Patients who have undergone an ileal pouch-anal anastomosis procedure often describe specific food sensitivities that may require diet alteration, even more so than do patients with permanent ileostomy. There may be roles for postoperative probiotic supplementation in an attempt to decrease the rate of "pouchitis" and appropriate preoperative nutrition support to minimize the risk of perioperative complications. PMID- 20581319 TI - Nutrition in hepatic encephalopathy. AB - Protein calorie malnutrition (PCM) is a well-known complication of chronic liver disease (CLD). A major contribution to PCM in CLD is restriction of dietary protein intake. After many decades of injudicious reduction in dietary protein, cirrhotic patients are now prescribed appropriate amounts of protein. PCM in CLD is known to be associated with life-threatening complications. In the general approach to these patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Most patients tolerate a normal amount of dietary protein without developing hepatic encephalopathy (HE). Oral branched-chain amino acids (BCAAs) have a limited role in HE. Patients who exhibit dietary protein intolerance originally were thought to be best treated with BCAA formulations. Mixed evidence has been reported in multiple studies. In keeping with other reports, this article shows that in animal protein-intolerant patients, even those with advanced cirrhosis, vegetable protein-based diets are well tolerated. Another approach to management of apparent dietary intolerance is to optimize HE treatment with available medications. This article reviews the causes of HE, minimal HE, and PCM; examines nutrition requirements and assessment; and discusses treatment options for malnutrition in HE. PMID- 20581320 TI - Dietary tyramine restriction for hospitalized patients on linezolid: an update. AB - Linezolid is a weak, reversible monoamine oxidase inhibitor. The current practice at most hospitals is to place patients receiving linezolid on a tyramine restricted diet. This process typically involves both the hospital's pharmacy department and the food and nutrition department. A literature search assessing the interaction between linezolid and tyramine was conducted, and the amount of tyramine in a typical unrestricted diet for a hospitalized patient was reviewed. Although patients receiving linezolid should avoid consuming large amounts of foods containing high concentrations of tyramine, such foods in large amounts are not components of meals for inpatients. Therefore, dietary tyramine restriction in hospitalized patients is not generally required. PMID- 20581321 TI - Dietitians and small bowel feeding tube placement. AB - Some advanced practice nutrition support dietitians have added small bowel feeding tube placement to their scope of responsibility. This is due, in part, to the challenges of gaining early enteral access in patients with functioning GI tracts. Emerging literature supports the practice of skilled practitioners placing feeding tubes at bedside. A variety of methods can be used to place tubes at the bedside. The nutrition support dietitian must understand licensure and liability considerations to perform this invasive procedure. This article will review literature reports of dietitians placing feeding tubes and provide information on the methods used, training and competencies required, and legal issues involved. PMID- 20581322 TI - Metabolic effects of cyclic parenteral nutrition infusion in adults and children. AB - BACKGROUND: Cyclic (discontinuous) infusion of parenteral nutrition (PN) presents a clear practical advantage over continuous 24-hour infusion in patients receiving long-term or home PN. It is important for nutrition support clinicians to recognize the metabolic consequences of cyclic infusion. METHODS: A literature search was conducted through PubMed (1948 to December 2009) and MEDLINE (1950 to November 2009) using the search term parenteral nutrition plus any of the following: cycling, cycle, cyclic, discontinuous, intermittent, bolus. Prospective clinical studies characterizing the metabolic effects of cyclic PN infusion in humans and their references were reviewed. RESULTS: Twenty-five studies met inclusion criteria and were included in the review. Sample sizes were 4-65 (18 studies examined < or =20 patients, 9 examined < or =10 patients). Eight studies had important design elements that limit interpretability. Cyclic and continuous PN infusions result in similar nitrogen balance and circulating counterregulatory hormone concentrations. Following PN infusion, carbohydrate oxidation decreases, fat oxidation increases, and the respiratory quotient decreases. In acutely ill mechanically ventilated patients, carbon dioxide production increases. Cyclic infusion may stabilize liver function tests in some patients with mild hyperbilirubinemia (< or =20 ng/mL) on continuous PN infusion. Abrupt infusion initiation may cause hyperglycemia. Abrupt discontinuation may cause hypoglycemia, predominantly in children younger than 2-3 years old, which may decrease with infusion tapering. Cyclic PN infusion is not associated with increased daily calcium, phosphorus, magnesium, or vitamin D losses. CONCLUSIONS: These results indicate a favorable risk-benefit profile of cyclic PN infusion in most patients receiving long-term or home PN, in support of current practices. PMID- 20581323 TI - Candidemia incidence in recipients of parenteral nutrition. AB - BACKGROUND: The purpose of this study was to assess the incidence of candidemia in recipients of parenteral nutrition (PN) in a tertiary medical center with disease-specific guidelines for appropriate PN use. METHODS: A retrospective, medical record/database review was conducted for adult patients who received PN in a 473-bed medical center from January 2006 to October 2008. Patients receiving PN >72 hours with no recent history of fungemia or concomitant antifungal therapy were evaluated for candidemia incidence with special interest in intensive care unit (ICU) patients. Epidemiological and clinical factors promoting candidemia development, pattern of systemic antifungal therapy use, and patient outcomes were investigated. RESULTS: Of 286 PN recipients, 14 (4.9%) patients were diagnosed with new-onset candidemia, with an incidence rate of 1.6 episodes per 1000 hospital-days. In the subgroup of 177 ICU patients, 11 (6.2%) patients developed candidemia, with an incidence rate of 2.4 episodes per 1000 ICU-days. PN duration was significantly longer in the candidemia group, with a median of 17 (4-53) days compared with 8 (4-124) days in the noncandidemia group (P = .013). Severity of illness was defined as major to extreme in 83.5% of patients. Hospital mortality in the candidemia group was greater than in the noncandidemia group (35.7% vs 16.2%, P = .058). CONCLUSIONS: Guidelines for PN therapy appropriately limit unnecessary use of PN but also select out severely ill patients who are at high risk for the development of candidemia. This study generates questions for future studies, including the benefits of empirical antifungal therapy in high-risk PN recipients. PMID- 20581324 TI - Use of home parenteral nutrition in patients with intra-abdominal desmoid tumors. AB - BACKGROUND: Fistulae, small bowel obstruction (SBO), and malabsorption are complications of intra-abdominal desmoid (IAD) tumors that require home parenteral nutrition (HPN). HPN outcomes in patients with IAD tumors have not been previously reported. The aim of this study was to compare some of the nutrition parameters and complications of HPN in patients with IAD with a control group of patients on HPN. METHODS: This was a case-control study of patients and randomly selected controls who required HPN because of fistulae, SBO, or malabsorption and were managed by the Cleveland Clinic Nutrition Support Team between 1990 and 2008. Variables included demographics, indications, number of episodes, duration of HPN, number of admissions and complications related to HPN, and nutrition parameters. Univariable and multivariable logistic regression analyses were used. RESULTS: Eighteen of 1615 HPN patients (1.1%) had IAD. For the study, 58 patients were included: 14 with IAD and 44 controls. Four IAD patients did not have complete medical records. IAD patients had longer duration of HPN (P = .015), were younger (P = .028), and were more likely to receive HPN for malabsorption (P < .001). Body mass index (BMI), serum albumin level, protein intake provided at the beginning of HPN, energy intake provided at the start and end of HPN, mortality, and complications were comparable between groups. At the end of HPN, IAD patients received significantly more protein and had lower serum albumin levels compared with controls. CONCLUSIONS: HPN for IAD patients maintained BMI but did not increase serum albumin concentration despite receiving more protein than controls. IAD patients did not have increased HPN-related complications. PMID- 20581325 TI - Home enteral nutrition: outcomes relative to indication. AB - BACKGROUND: Home enteral nutrition (HEN) is a life-sustaining therapy for patients who are unable to meet nutrient needs by oral intake, who have a functional gastrointestinal (GI) tract, and who are able to remain in their own home. The objective of this study was to identify whether the indication for HEN is related to reason for discharge from a HEN program. METHODS: A retrospective chart review of all patients admitted to the multidisciplinary Northern Alberta Home Enteral Nutrition Support Program between January 1, 1999 and January 1, 2005 was performed. Detailed information on the indication for HEN, length of time on program, and reason for discharge was collected and statistically analyzed. RESULTS: Over the 6-year period, 727 adult patients were admitted. Major diagnostic categories for HEN were cancer, neurological disorders, and GI disorders. Median duration of HEN for cancer patients was 122 (range, 1-1259) days, duration for neurological disorders was 187 (range, 1-1752) days, and duration for GI disorders was 161 (range, 1-1849) days. Death was the main reason for discharge in patients with cancer and neurological disorders. Patients with GI disorders were most likely to initiate oral intake and least likely to be discharged because of death. CONCLUSIONS: Indications for HEN are related to outcome-specifically, time to discontinuation of enteral nutrition and reason for discharge, including return to oral intake and death. PMID- 20581326 TI - Colonic ischemia and perforation associated with enteral feeding through an ileal tube. AB - Reported complications of enteral feeding through a jejunostomy include diarrhea, intraperitoneal leaks, bowel obstruction, fistula formation, wound infection, tube occlusion, and other mechanical malfunctions. However, the incidence of these complications is very low, and many physicians prefer to feed their patients by means of a jejunal tube instead of parenteral nutrition. A potentially lethal complication is ischemia of the bowel distal to the site of insertion of the feeding catheter. The described cases of bowel ischemia secondary to enteral nutrition invariably occurred at the level of the jejunum. This report describes an unusual case of perforation of the colon in a patient fed through an erroneously placed feeding catheter in the distal ileum, just proximal to the ileocecal valve. After weeks of continuous and intractable diarrhea and progressive weight loss, the patient developed diffuse colonic ischemia with subsequent free perforation of the left colon and peritonitis. Surgical treatment consisted of placement of a new feeding tube in the proximal jejunum and removal of the old one together with a short segment of small bowel, left hemicolectomy, and end colostomy. The patient tolerated the procedure well, the tube feedings were gradually restarted, and at the 6-month postoperative visit gastrointestinal function was normal. This case illustrates possible complications of an inadvertently placed feeding tube. Not only may it cause unexplained diarrhea and undernutrition, but it may lead to more serious events like colonic ischemia and perforation. PMID- 20581327 TI - Hypoalbuminemia in a cystic fibrosis patient with severe erosive esophagitis. AB - An 8-year-old patient with cystic fibrosis presented with hypoalbuminemia as the main symptom of severe erosive esophagitis. Extensive evaluation failed to reveal a nutrition, pancreatic, intestinal, or renal explanation of his hypoalbuminemia. Identification and treatment of the esophagitis led to resolution of the hypoalbuminemia. PMID- 20581328 TI - Popular diets prescribed by alternative practitioners--part 2. PMID- 20581330 TI - The evolutionary history of archaeal MCM helicases: a case study of vertical evolution combined with hitchhiking of mobile genetic elements. AB - Genes encoding DNA replication proteins have been frequently exchanged between cells and mobile elements, such as viruses or plasmids. This raises potential problems to reconstruct their history. Here, we combine phylogenetic and genomic context analyses to study the evolution of the replicative minichromosome maintenance (MCM) helicases in Archaea. Several archaeal genomes encode more than one copy of the mcm gene. Genome context analysis reveals that most of these additional copies are encoded within mobile elements. Exhaustive analysis of these elements reveals diverse groups of integrated archaeal plasmids or viruses, including several head-and-tail proviruses. Some MCMs encoded by mobile elements are structurally distinct from their cellular counterparts, with one case of novel domain organization. Both genome context and phylogenetic analysis indicate that MCM encoded by mobile elements were recruited from cellular genomes. An accelerated evolution and a dramatic expansion of methanococcal MCMs suggest a host-to-virus-to-host transfer loop, possibly triggered by the loss of the archaeal initiator protein Cdc6 in Methanococcales. Surprisingly, despite extensive transfer of mcm genes between viruses, plasmids, and cells, the topology of the MCM tree is strikingly congruent with the consensus archaeal phylogeny, indicating that mobile elements encoding mcm have coevolved with their hosts and that DNA replication proteins can be also useful to reconstruct the history of the archaeal domain. PMID- 20581332 TI - Expression and functions of fibroblast growth factor 2 (FGF-2) in hippocampal formation. AB - Among the 23 members of the fibroblast growth factor (FGF) family, FGF-2 is the most abundant one in the central nervous system. Its impact on neural cells has been profoundly investigated by in vitro and in vivo studies as well as by gene knockout analyses during the past 2 decades. Key functions of FGF-2 in the nervous system include roles in neurogenesis, promotion of axonal growth, differentiation in development, and maintenance and plasticity in adulthood. From a clinical perspective, its prominent role for the maintenance of lesioned neurons (e.g., ischemia and following transection of fiber tracts) is of particular relevance. In the unlesioned brain, FGF-2 is involved in synaptic plasticity and processes attributed to learning and memory. The focus of this review is on the expression of FGF-2 and its receptors in the hippocampal formation and the physiological and pathophysiological roles of FGF-2 in this region during development and adulthood. PMID- 20581333 TI - StatBite: SEER incidence of brain and other nervous system cancers 1992-2007. PMID- 20581331 TI - Glial cells and chronic pain. AB - Over the past few years, the control of pain exerted by glial cells has emerged as a promising target against pathological pain. Indeed, changes in glial phenotypes have been reported throughout the entire nociceptive pathway, from peripheral nerves to higher integrative brain regions, and pharmacological inhibition of such glial reactions reduces the manifestation of pain in animal models. This complex interplay between glia and neurons relies on various mechanisms depending both on glial cell types considered (astrocytes, microglia, satellite cells, or Schwann cells), the anatomical location of the regulatory process (peripheral nerve, spinal cord, or brain), and the nature of the chronic pain paradigm. Intracellularly, recent advances have pointed to the activation of specific cascades, such as mitogen-associated protein kinases (MAPKs) in the underlying processes behind glial activation. In addition, given the large number of functions accomplished by glial cells, various mechanisms might sensitize nociceptive neurons including a release of pronociceptive cytokines and neurotrophins or changes in neurotransmitter-scavenging capacity. The authors review the conceptual advances made in the recent years about the implication of central and peripheral glia in animal models of chronic pain and discuss the possibility to translate it into human therapies in the future. PMID- 20581334 TI - Low awareness of and referral to National Cancer Information Resources among physicians. PMID- 20581335 TI - Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. AB - In 2005, the American Academy of Neurology and the Child Neurology Society published a practice parameter, based primarily on studies that involved 6 to 18 months of treatment, indicating that prednisone has a beneficial effect on muscle strength and function in patients with Duchenne muscular dystrophy and recommended that corticosteroids be offered (prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d) as treatment. Recent reports emphasize that longer term treatment with corticosteroids (greater than 3 years) produces important sustained benefits in neuromuscular function without causing major side effects. This review highlights these reports and indicates that long-term corticosteroid therapy (1) prolongs ambulation by 2 to 5 years, (2) reduces the need for spinal stabilization surgery, (3) improves cardiopulmonary function, (4) delays the need for noninvasive nasal ventilation, and (5) increases survival and the quality of life of patients with Duchenne muscular dystrophy. Educational, vocational, and other social counseling is now a vital part of management for Duchenne muscular dystrophy. PMID- 20581337 TI - Motor learning principles for rehabilitation: a pilot randomized controlled study in poststroke patients. AB - BACKGROUND: Six months after a stroke, the hemiplegic arm often remains compromised. More innovative approaches to motor rehabilitation are needed. OBJECTIVE: The authors compared a motor learning-based approach in a virtual environment with more conventional upper extremity therapy in a pilot trial. METHODS: This prospective, single-blinded, randomized controlled trial compared reinforced feedback in a virtual environment (RFVE; n = 27) with a control intervention (n = 20) of progressive therapy for the affected upper extremity. Both treatments were provided for 4 weeks, 5 days per week, with 1-hour treatment sessions daily. The primary outcomes were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scores. Kinematic outcomes included mean duration (MD), mean linear velocity (MLV), and number of submovements to measure the motor performance. Analyses of the primary outcomes were performed per protocol and by intention to treat. RESULTS: F-M UE scores improved significantly in the RFVE group compared with the conventional therapy group ("intention to treat" = 5.10 points, P = .004; ANCOVA = 4.26 points, P < .01). Several of the kinematic parameters improved in the RFVE group (MD, P < .01; MLV, P < .01). FIM improvements did not differ. CONCLUSIONS: Both rehabilitation therapies improved arm motor performance and functional activity, but the RFVE therapy induced more robust results in patients exposed to late rehabilitation treatment. PMID- 20581338 TI - The effects of Internet-based home training on upper limb function in adults with cerebral palsy. AB - BACKGROUND: While adults with hemiplegic cerebral palsy (CP) can have significant upper limb dysfunction, the effects of movement-based training has not been investigated. OBJECTIVE: This uncontrolled trial assessed the effects of a home and internet-based upper limb intervention program targeting motor and sensory function. METHODS: Twelve adults, aged 21 to 57 yrs, GMFCS levels I-III with asymmetric upper limb involvement participated in the Upper Limb Training and Assessment (ULTrA) program. Clinical and functional measures included the Motor Activity Log (MAL), the Nine-Hole Peg test, and grip strength. An upper limb training system consisting of a laptop, webcam, target light board, and hand manipulation/ discrimination devices was installed in each participant's home. Training occurred 40 min/day, 5 days/wk for 8 wks and included both unilateral and bilateral reach movements as well as a series of hand sensorimotor tasks such as card turning, stereognosis, and tactile discrimination. Data generated during each session were transmitted to the laboratory via the Internet. MAIN OUTCOME MEASURES: were movement time, interlimb delay time, and performance on hand sensorimotor tasks. RESULTS: Following training, affected limb reach movement time decreased significantly for unilateral and bilateral tasks. Interlimb delay during sequential reaching also decreased. Significant improvement in hand manipulation tasks was also seen. Compliance was excellent and there were no adverse effects. CONCLUSION: The ULTrA program had beneficial effects for adults with CP and is safe and convenient to use. This system contrasts sharply with programs with similar intent that require participant travel and hours of therapist-based intervention. PMID- 20581340 TI - Having a male co-twin masculinizes mental rotation performance in females. PMID- 20581339 TI - Executive function, memory, and gait speed decline in well-functioning older adults. AB - BACKGROUND: In community-dwelling older adults, global cognitive function predicts longitudinal gait speed decline. Few prospective studies have evaluated whether specific executive cognitive deficits in aging may account for gait slowing over time. METHODS: Multiple cognitive tasks were administered at baseline in 909 participants in the Health, Aging, and Body Composition Study Cognitive Vitality Substudy (mean age 75.2 +/- 2.8 years, 50.6% women, 48.4% black). Usual gait speed (m/s) over 20 minutes was assessed at baseline and over a 5-year follow-up. RESULTS: Poorer performance in each cognitive task was cross sectionally associated with slower gait independent of demographic and health characteristics. In longitudinal analyses, each 1 SD poorer performance in global function, verbal memory, and executive function was associated with 0.003-0.004 m/s greater gait speed decline per year (p =.03-.05) after adjustment for baseline gait speed, demographic, and health characteristics. CONCLUSIONS: In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging. PMID- 20581341 TI - Searching for life motion signals. Visual search asymmetry in local but not global biological-motion processing. AB - The visual search paradigm has been widely used to study the mechanisms underlying visual attention, and search asymmetry provides a source of insight into preattentive visual features. In the current study, we tested visual search with biological-motion stimuli that were spatially scrambled or that represented feet only and found that observers were more efficient in searching for an upright target among inverted distractors than in searching for an inverted target among upright distractors. This suggests that local biological-motion signals can act as a basic preattentive feature for the human visual system. The search asymmetry disappeared when the global configuration in biological motion was kept intact, which indicates that the attentional effects arising from biological features (e.g., local motion signals) and global novelty (e.g., inverted human figure) can interact and modulate visual search. Our findings provide strong evidence that local biological motion can be processed independently of global configuration and shed new light on the mechanisms of visual search asymmetry. PMID- 20581342 TI - Keeping your eyes on the prize: anger and visual attention to threats and rewards. AB - People's emotional states influence what they focus their attention on in their environment. For example, fear focuses people's attention on threats, whereas excitement may focus their attention on rewards. This study examined the effect of anger on overt visual attention to threats and rewards. Anger is an unpleasant emotion associated with approach motivation. If the effect of emotion on visual attention depends on valence, we would expect anger to focus people's attention on threats. If, however, the effect of emotion on visual attention depends on motivation, we would expect anger to focus people's attention on rewards. Using an eye tracker, we examined the effects of anger, fear, excitement, and a neutral emotional state on participants' overt visual attention to threatening, rewarding, and control images. We found that anger increased visual attention to rewarding information, but not to threatening information. These findings demonstrate that anger increases attention to potential rewards and suggest that the effects of emotions on visual attention are motivationally driven. PMID- 20581343 TI - Small wins big: analytic pinyin skills promote Chinese word reading. AB - The present study examined invented spelling of pinyin (a phonological coding system for teaching and learning Chinese words) in relation to subsequent Chinese reading development. Among 296 Chinese kindergartners in Beijing, independent invented pinyin spelling was found to be uniquely predictive of Chinese word reading 12 months later, even with Time 1 syllable deletion, phoneme deletion, and letter knowledge, in addition to the autoregressive effects of Time 1 Chinese word reading, statistically controlled. These results underscore the importance of children's early pinyin representations for Chinese reading acquisition, both theoretically and practically. The findings further support the idea of a universal phonological principle and indicate that pinyin is potentially an ideal measure of phonological awareness in Chinese. PMID- 20581344 TI - Predicting for human pharmaceutical cancer risk. PMID- 20581345 TI - Invited commentary: predicting human pharmaceutical cancer risk. PMID- 20581346 TI - Feline nerve sheath tumors versus feline peripheral nerve sheath tumors. PMID- 20581347 TI - Molecular confirmation of Parelaphostrongylus tenuis Infection in a horse with verminous encephalitis. PMID- 20581349 TI - Preterm birth, infection, and inflammation advances from the study of animal models. AB - Inflammation is a protective response mediated by both innate and adaptive arms of the immune system following exposure to a range of harmful stimuli. Although inflammation is an essential mechanism in response to challenges including tissue injury and microbiological insult, inappropriate or excessive induction of the inflammatory response is itself a well-characterized cause of morbidity and mortality in adult populations. There is currently a growing appreciation of the potential for inflammation to play an adverse role in fetal health. The expression of cytokines (notably interleukin 1beta [IL-1beta], IL-6, IL-8, and tumor necrosis factor alpha [TNF-alpha]) by either the fetal or maternal tissues has been demonstrated to upregulate the activity of a number of uterine and cervical factors (eg, prostaglandin hormones and their receptors, matrix metalloproteinases, vascular endothelial growth factor [VEGF]), leading to premature initiation of the parturition process. Herein, we review important developments in our understanding of the link between preterm birth and fetal inflammation subsequent to infection, gained from studies undertaken in animal models. PMID- 20581350 TI - Isolation and characterization of side population cells in the postpartum murine endometrium. AB - Endometrium is a highly active organ that is periodically remodeled during the life span. Previous studies have indicated the presence of an adult stem or progenitor cell population in this tissue. In this study, side population (SP) cells were isolated from the endometrium of postpartum murine uterus but not from the endometrium of a uterus undergoing a normal estrus cycle. Phenotype analysis showed that SP cells were negative for hematopoietic, endothelial, and mesenchymal stem cell (MSC) markers, but they expressed stem cell antigen 1 (Sca 1) and c-kit at various degrees. Side population cell is a heterogeneous population of endometrial stem/progenitor cells that have colony-forming capacity. They were found to reside in quiescence in the stroma but not in the luminal epithelium. These data suggest that, like other tissues and organs, the murine endometrium also contains SP cells. Their specific role in the regeneration of the endometrium warrants further study. PMID- 20581352 TI - Efficacy of a tin/fluoride rinse: a randomized in situ trial on erosion. AB - Concentrated tin- and fluoride-containing mouthrinses are effective erosion inhibitors in enamel and dentin. To test whether this is also true for solutions with lower concentrations, we conducted a randomized double-blind three-cell crossover in situ study with extra-orally performed erosive impacts (citric acid, 6 x 5 min/day) and an intra-oral rinsing protocol (1 x 30 sec/day) in 24 volunteers. The mouthrinses were a placebo, a NaF (500 ppm F-), and an amine fluoride (AmF)/NaF/SnCl2 mouthrinse (500 ppm F-, 800 ppm Sn(2+)). Compared with the placebo, the NaF mouthrinse reduced substance loss by 19% in enamel and 23% in dentin (p <= 0.01 each); the AmF/NaF/SnCl2 mouthrinse reduced this parameter by 67% in enamel and 47% in dentin (p <= 0.001 each). AmF/NaF/SnCl2 was significantly more effective than NaF in both tissues (p <= 0.01). The mouthrinse containing Sn and F exhibited good efficacy, even under severe erosive conditions. PMID- 20581351 TI - The impact of vitamin C supplementation in pregnancy and in vitro upon fetal membrane strength and remodeling. AB - Generation of reactive oxygen species (ROS) has been suggested as a mechanism of fetal membrane (FM) weakening leading to rupture, particularly with preterm premature rupture of the fetal membranes (PROM). In vitro, FM incubation with tumor necrosis factor (TNF) mimics physiological FM weakening, concomitant with generation of ROS and collagen remodeling. Proinflammatory cytokines are also postulated to have a role in the development of the FM physiological weak zone where rupture normally initiates in-term gestations. We hypothesized that antioxidant treatment may block ROS development and resultant FM weakening. Two studies examining antioxidant effects upon FM strength were conducted, one in vivo and the other in vitro. Fetal membrane of patients enrolled in a multicenter placebo-controlled trial to determine the effect of vitamin C (1 g/day) and vitamin E (400 IU/day) upon complications of pre-eclampsia were examined for FM biomechanical properties and biochemical remodeling at birth. Separately, biomechanics and biochemical markers of remodeling were determined in FM fragments incubated with TNF with or without vitamin C preincubation. Supplemental dietary vitamin C in combination with vitamin E did not modify rupture strength, work to rupture, or matrix metalloproteinase-9 (MMP9; protein or activity) either within or outside the term FM physiological weak zone. In vitro, TNF decreased FM rupture strength by 50% while increasing MMP9 protein. Vitamin C did not inhibit these TNF-induced effects. Vitamin C alone had a weakening effect on FM in vitro. We speculate that vitamin C supplementation during pregnancy will not be useful in the prevention of preterm PROM. PMID- 20581353 TI - Design, operation, and interpretation of clinical trials. AB - Randomized controlled clinical trials offer the best evidence for changing clinical practice and informing public health policy. Using examples from the literature, this paper reviews clinical trials for those who may be unfamiliar with their design, operation, and interpretation. In the design of a clinical trial, the question to be answered and a clinically meaningful outcome must be clearly defined. Ethics must be considered, sample size carefully estimated, and use of biomarkers and surrogate outcomes understood. Prominent issues in trial implementation include developing a manual of operations, trial registration, subject recruitment and retention, use of a data coordinating center, and data and safety monitoring. Interpretation of clinical trials requires understanding differences between efficacy and effectiveness; superiority, equivalence, and non inferiority; intent-to-treat; primary and secondary analyses; and limitations of unregistered small clinical trials compared with large multi-center Phase III trials that are more likely to be representative of a population and change clinical practice or public health policy. PMID- 20581354 TI - Fluoride and chlorhexidine release from filled resins. AB - Resin-based materials that release either fluoride or chlorhexidine have been formulated for inhibiting caries activity. It is not known if the two agents, when incorporated into one material, would interact and affect their release potential. We hypothesized that the ratio of fluoride to chlorhexidine incorporated into a resin, and the pH of the storage medium, will affect their releases from the material. The material investigated contained 23 wt% of filler, and the ratios of calcium fluoride to chlorhexidine diacetate were 8/2, 5/5, and 2/8. The release was conducted in pH 4, 5, and 6 acetate buffers. The results showed that release of either agent increased as the pH of the medium decreased. The presence of fluoride salt substantially reduced the chlorhexidine release, while the presence of a specific quantity of chlorhexidine significantly increased fluoride release. This interaction can be utilized to optimize the release of either agent for therapeutic purposes. PMID- 20581356 TI - Getting clients to comply. PMID- 20581355 TI - Early dexamethasone relieves trigeminal neuropathic pain. AB - The analgesic effects of dexamethasone on neuropathic pain have been controversial. The present study investigated the effects of dexamethasone on mechanical allodynia in rats with mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to injure the inferior alveolar nerve. Nociceptive behavior was examined on each designated day after surgery. Mal-positioned dental implants significantly decreased air-puff thresholds both ipsilateral and contralateral to the injury site. Distinct mechanical hyperalgesia and cold and thermal hypersensitivity were also observed bilaterally. Daily administration of dexamethasone produced prolonged anti-allodynic effects (25 or 50 mg/kg, i.p.), but failed to reduce mechanical allodynia when it had already been established. Therefore, our findings provide that early treatment with dexamethasone is important in the treatment of nociceptive behavior suggestive of trigeminal neuropathic pain. PMID- 20581357 TI - Equine disease surveillance, January to March 2010. PMID- 20581358 TI - Risk factors for tail injuries in dogs in Great Britain. AB - The aim of the current study was to quantify the risk of tail injury, to evaluate the extent to which tail docking reduces this risk, and to identify other major risk factors for tail injury in dogs in Great Britain. A nested case-control study was conducted during 2008 and 2009. Data were obtained from a stratified random sample of veterinary practices throughout Great Britain, and questionnaires were sent to owners of dogs with tail injuries and owners of a randomly selected sample of dogs without tail injuries. The risks of injury were reported adjusting for the sampling approach, and mixed effects logistic regression was used to develop a multivariable model for risk factors associated with tail injury. Two hundred and eighty-one tail injuries were recorded from a population of 138,212 dogs attending 52 participating practices. The weighted risk of tail injuries was 0.23 per cent (95 per cent confidence interval 0.20 to 0.25 per cent). Thirty-six per cent of injuries were reportedly related to injuries sustained in the home, 17.5 per cent were outdoor-related injuries, 14.4 per cent were due to the tail being caught in a door, for 16.5 per cent the cause was unknown and the remainder were due to other causes. Dogs with a wide angle of wag and dogs kept in kennels were at significantly higher risk of sustaining a tail injury. Dogs with docked tails were significantly less likely to sustain a tail injury; however, approximately 500 dogs would need to be docked in order to prevent one tail injury. English springer spaniels, cocker spaniels, greyhounds, lurchers and whippets were all at significantly higher risk when compared to labradors and other retrievers. Differences between countries (England, Scotland and Wales) and between rural and urban environments were not significant. PMID- 20581359 TI - Development and use of an indirect ELISA in an outbreak of bovine besnoitiosis in Spain. AB - An indirect ELISA based on a soluble extract of Besnoitia besnoiti tachyzoites was developed and standardised. A set of positive and negative reference bovine sera were characterised using an immunofluorescence antibody test and Western blot. A cut-off with a relative index per cent of 8.1 was determined for equal sensitivity and specificity (100 per cent) by two-graph receiver operating characteristic analysis. Cross-reactions with other closely related Apicomplexan parasites were discarded. The standardised ELISA was then used during an outbreak of bovine besnoitiosis in a mountainous area of central Spain. The outbreak occurred in nine herds, and 358 animals that shared grazing lands during the summer season were affected. Clinical examination and blood sampling were carried out for all animals, and skin biopsies were obtained from animals with skin lesions. The confirmatory diagnosis was carried out by means of the indirect ELISA, together with the identification of tissue cysts by microscopy. Most of the animals were seropositive (90.5 per cent), but only 43 per cent of seropositive cattle developed clinical signs compatible with besnoitiosis. Additionally, a significant increase in seroprevalence and clinical signs was found to be associated with the increasing age of the animals, suggesting rapid horizontal transmission of the disease. PMID- 20581360 TI - Reduction of workplace contamination with platinum-containing cytostatic drugs in a veterinary hospital by introduction of a closed system. AB - The objective of this study was to determine the level of workplace contamination with platinum-containing cytostatic drugs in a veterinary hospital. A closed chemotherapy application system was then added to the safety regimen. Workplace contamination was measured over a nine-month period by taking wipe samples from seven locations. Before the introduction of the closed system, amounts of platinum were detected at four locations. After the introduction of the closed system, there was a temporary increase in contamination at two locations, followed by an overall reduction in contamination by the end of the study period. PMID- 20581361 TI - Sequence type 398 meticillin-resistant Staphylococcus aureus infection and colonisation in dogs. PMID- 20581362 TI - Detection of Mycoplasma bovis in cattle with mastitis and respiratory problems in eastern Turkey. PMID- 20581366 TI - Role of immunity in the management and control of bovine coccidiosis. PMID- 20581368 TI - Exposure to Encephalitozoon cuniculi in rabbits with dental disease. PMID- 20581369 TI - Blood transfusions in cats. PMID- 20581370 TI - Introduction: Advances in early detection of reading risk. PMID- 20581371 TI - An exploratory study of the development of early syllable structure in reading impaired children. AB - Babbling between the ages of 8 and 19 months was examined in 19 children, 13 of whom were at high risk for reading disorder (RD) and 6 normally reading children at low familial risk for RD. Development of syllable complexity was examined at five periods across this 11-month window. Results indicated that children who later evidenced RD produced a lower proportion of canonical utterances and less complex syllable structures than children without RD. As syllable complexity is an early indicator of phonological sophistication, differences at this level may offer a window into how the phonological system of children with RD is structured. Future directions for this line of research are discussed. PMID- 20581372 TI - Epilogue to Journal of Learning Disabilities special edition "Advances in the early detection of reading risk": Future advances in the early detection of reading risk: Subgroups, dynamic relations, and advanced methods. PMID- 20581373 TI - Vitamin D and COPD: seasonal variation is important. PMID- 20581374 TI - Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. PMID- 20581375 TI - Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. AB - Objectives. The osteochondral junction can be a source of pain in both RA and OA. Growth of blood vessels and nerves from the subchondral bone into articular cartilage may mediate the association between joint pathology and symptoms. We have investigated associations between angiogenesis, inflammation and neurovascular growth factor expression at the osteochondral junction in human arthritis. Methods. Osteochondral junctions from medial tibial plateaux of patients undergoing arthroplasty for RA (n = 10) or OA (n = 11), or from non arthritic post-mortem controls (n = 11) were characterized by immunohistochemistry for CD34 and smooth muscle alpha-actin (blood vessels), CD68 (macrophages), CD3 (lymphocytes), proliferating cell nuclear antigen, vascular endothelial, platelet-derived and nerve growth factor (NGF). Results. Osteochondral angiogenesis was demonstrated as increased endothelial cell proliferation and vascular density in non-calcified articular cartilage, both in RA and OA. Osteochondral angiogenesis was associated with subchondral bone marrow replacement by fibrovascular tissue expressing VEGF, and with increased NGF expression within vascular channels. RA was characterized by greater lymphocyte infiltration and PDGF expression than OA, whereas chondrocyte expression of VEGF was a particular feature of OA. NGF was observed in vascular channels that contained calcitonin gene-related peptide-immunoreactive sensory nerve fibres. Conclusions. Osteochondral angiogenesis in RA and OA is associated with growth factor expression by cells within subchondral spaces, vascular channels and by chondrocytes. NGF expression and sensory nerve growth may link osteochondral angiogenesis to pain in arthritis. PMID- 20581376 TI - Estimation of health care costs as a function of disease severity in people with psoriatic arthritis in the UK. AB - OBJECTIVES: The primary aim of this study was to estimate annual health care costs for biologic-naive patients with PsA in the UK. The relationship between disease severity, defined by physical limitations, and costs was also explored. METHODS: This study utilized data from the British Society of Rheumatology Biologics Register (BSRBR) to develop a multivariate model estimating disease severity from parameters available in routine primary care data. The HAQ Disability Index was used to determine disease severity. This algorithm was then applied to routine data from The Health Improvement Network (THIN). Annual costs were estimated for drugs, contacts with a general practitioner and other health care professionals, tests, hospital outpatient attendances and inpatient admissions from a National Health Service perspective using official tariffs. The relationship between disease severity and health care costs was estimated using a generalized linear model. RESULTS: Three hundred and fifty-six cases with PsA were identified in the BSRBR and 4492 in THIN. Total mean annual health care costs ranged from L11 to L20 782 with a mean of L1446 (s.d. L1756). When costs were sub-grouped by the predicted HAQ score, the mean annual observed costs ranged from L548 per person for the least severely affected (HAQ <= 1.2) to L4832 for the most severely affected (HAQ > 2.6). Prescription costs and secondary care episodes accounted for more than a third of total care costs each (38 and 34%, respectively). When the relationship between disease severity and costs was examined, estimated HAQ was found to be a significant predictor of total health care costs. CONCLUSIONS: Treatment of people with PsA resulted in considerable financial costs and these costs varied markedly by disease severity. PMID- 20581377 TI - Intravenous fluid resuscitation: was Poiseuille right? AB - AIM: To compare the flow rates of readily available intravenous infusion devices and to compare the effect of the addition of pressure or a needle-free intravenous connector device. METHODS: Several intravenous devices with different characteristics had their flow rates determined under a standard set of conditions. The flow rates were then measured with the addition of a pressure bag to the system and then with a needle-free intravenous connector device. The flow rates and change in flow rates were then analysed. RESULTS: The results showed a general agreement with Poiseuille's law. The needle-free connector slowed the rate of flow by up to 41.4% with the greatest effect on short, wide-bore devices. The addition of pressure had a greater effect on longer devices. CONCLUSIONS: Short, wide cannulae should be used when rapid fluid resuscitation is required. Needle-free devices should not be used when rapid fluid resuscitation is needed. PMID- 20581378 TI - The use of bedside ultrasound to diagnose posterior sterno-clavicular dislocation. PMID- 20581379 TI - Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. AB - BACKGROUND: There is evidence of increasing use of the synthetic cathinone mephedrone (4-methylmethcathinone), particularly amongst clubbers. However, there have only two single case reports of mephedrone toxicity. The aim of this study is to report the pattern of clinical toxicity seen with mephedrone use. CASE SERIES: We describe 15 patients who presented to our Emergency Department following self-reported mephedrone use. Significant clinical features seen included agitation in 53.3%, tachycardia in 40%, systolic hypertension in 20% and seizures in 20%. Twenty per cent required treatment with benzodiazepines, predominantly for management of agitation. All patients were discharged with no sequelae. Previous user reports have suggested that mephedrone use is associated with cool/blue peripheries; this was not seen in any of the patients in our series. CONCLUSION: The pattern of toxicity seen with mephedrone in this series is similar to that seen with 1-benzylpiperazine which has recently been classified under UK and EU misuse of drugs legislation. On the basis of this, together with a recent confirmed mephedrone related death in Sweden, we feel that appropriate assessments should be undertaken to determine the legal status of mephedrone. PMID- 20581380 TI - Early aeromedical transfer after acute coronary syndromes. AB - AIMS: To investigate the safety and efficacy of early aeromedical transfer after acute coronary syndromes (ACS). The Island of Jersey is 160 km from the UK and as no catheter laboratory facilities exist locally, patients with ACS are transferred to tertiary centres by air ambulance in the UK for further investigations. METHODS: All patients transferred to the UK for investigation after ACS in 2008 were identified retrospectively from coronary care admission records and the local flight transfer database. Data were collected on patient demographics, diagnosis, time from presentation, flight duration, accompanying personnel and in-flight complications. Significant complications were defined as death, cardiac or respiratory arrest, sustained arrhythmia requiring electrical cardioversion or the need for endotracheal intubation. RESULTS: 65 patients (mean age 61.7 years; 80.0% male) were transferred for cardiac catheterisation after non-ST elevation myocardial infarction (n=30, 46.2%) or ST elevation myocardial infarction (n=23, 35.4%), or with unstable angina (n=12, 18.5%). Patients were transferred 3.6 +/- 3.4 days after presentation; mean transfer time was 171.6 +/- 38.8 min. The majority (90.8%) of patients were transferred with both a doctor and a nurse. There were no significant complications during transfer. Intra transport medication with nitrates, diuretics, analgesia, antiemetics or antiarrhythmics was required in 15 (23.1%) patients. CONCLUSIONS: Aeromedical transfer after ACS is safe within 3 days of presentation. Given the minor nature of in-flight complications, a paramedic and coronary care nurse are sufficient medical escort for these patients. PMID- 20581381 TI - An unusual contraindication to the use of non-invasive ventilation in A&E. PMID- 20581382 TI - Deaths from trauma in London--a single centre experience. AB - INTRODUCTION: Trauma data collection by UK hospitals is non-mandatory and data regarding trauma mortality are deficient. Our aim was to provide a contemporary description of mortality in a maturing trauma-receiving hospital serving an inner city population. METHODS: A prospectively maintained registry was analysed for demographics; injury mechanism; and time, location and cause of death in trauma patients admitted via the Emergency Department between 2004 and 2008. RESULTS: 4986 trauma team activations yielded 4243 complete cases. The number of patients rose from 784 in 2004-2005 to 1400 in 2007/8. 302 (7%) of these died. All-cause mortality fell from 8.8% to 5.8% (p=0.0075). Blunt trauma (predominantly falls from height and road traffic collisions) accounted for 79% of admissions but 87% of mortality. Penetrating trauma accounted for 21% of admissions and 13% of mortality. Most penetrating injury deaths were from stabbing injury (31/40) as opposed to gunshot wounds (8/40). The biggest cause of death was central nervous system injury (47.7%) followed by haemorrhage (26.2%). Penetrating injury death was associated with marked shock and acidosis compared to blunt mechanisms--mean (SD) admission systolic blood pressure 25.4 (45.7) versus 105.5 (60.5) mm Hg; mean (SD) base excess -21.84 (7.2) versus 9.71 (8.45) mmol, respectively. No classical trimodal distribution of death was observed. CONCLUSION: Despite current focus on death from knife and gun crime, the vast majority of trauma mortality arises from blunt aetiology. Maturation of our systems of care has been associated with a drop in mortality as institutional trauma volumes increase and clinical infrastructure develops. PMID- 20581383 TI - Improving emergency care pathways: an action research approach. AB - BACKGROUND: Clinicians and managers across specialities are under pressure to review treatment and referral pathways to enable evidence-based practice, improve patient flow and provide a seamless service. This study outlines the processes and outcomes of an action research study conducted to reduce inappropriate attendances and unplanned pressures on Emergency Department (ED) staff in an English hospital during 2006-2008. METHODS: Action research, comprising three action/reflection cycles conducted with participants, was used. Data were collected using retrospective patient record review (n=35,200) interviews with staff members (n=28), observation of patient pathways (n=38 patients) and measurement of team climate (n=31) with literature reviews also informing each cycle of data collection. RESULTS: ED attendance and hospital emergency admission data were largely similar to the national picture with regards to time/day of attendance and seasonal variation. However, in the 'adult majors' subgroup, mean attendance on a Monday was significantly higher than the rest of the week (p<0.001) and 36% were self-referrals. Observation data revealed that patients were informally assessed by reception staff and directed to majors or minors; this practice was replaced by reinstatement of triage. Patients identified as 'inappropriate' were managed inconsistently, irrespective of department workload. ED attendance decreased as the project progressed and the number of attendees resulting in hospital admission rose slightly. CONCLUSIONS: Study data suggest that inappropriate attendances decreased; however, data collection exposed gaps in the existing management information systems and inconsistencies in working practices in the ED. Action research can have a practical value besides contributing to knowledge. PMID- 20581384 TI - Effect of PON1 on dichlorvos toxicokinetics. AB - OBJECTIVES: To provide toxicokinetic and clinical evidence of the hydrolytic effect of paraoxonase-1 (PON1) on acute organophosphate poisoning in rats. METHODS: 40 male Wistar rats were randomised into four equal groups. Dichlorvos administration group (A group) underwent dichlorvos injection (dissolved in corn oil) using intraperitoneal (ip) dose of 10 mg/kg. PON1 pretreatment group (B group) was injected with PON1 in the tail vein (intravenous), dose 9600 U/kg, 30 min prior to dichlorvos administration. In the treatment group (C group), atropine 0.05 mg/kg and pyraloxime chloride (PAM-CI) 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Finally, in the co treatment group (D group), PON1 was injected intravenously with a dose of 9000 U/kg 30 min prior to dichlorvos administration; atropine 0.05 mg/kg and PAM-CI 120 mg/kg were injected intravenously within 2 min after dichlorvos administration. Blood was collected after administration. Plasma dichlorvos concentration was detected by liquid chromatography-mass spectra (LC-MS) method and clinical signs were observed. Toxicokinetic parameters were calculated in a statistical moment model. RESULTS: AUC (0->infinity) in group B was statistically different from that in groups A and C (p<0.05), while it was not different from group D (p>0.05); there was no statistical difference between group A and group C (p>0.05). The statistical results of Cmax were the same as those of AUC (0 >infinity). There were no differences of MRT between four groups (p>0.05). Clinical signs can be improved by PON1 and atropine + PAM-CI, and co-treatment can relieve signs more effectively. CONCLUSION: PON1 can decrease the amount of dichlorvos that entered the blood, lowered the peak concentration and relieved clinical signs. PMID- 20581385 TI - Tympanic temperature during therapeutic hypothermia. AB - OBJECTIVE: Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia. METHODS: Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements. RESULTS: Compared with oesophageal temperature, bladder temperature had a bias of 0.019 degrees C (limits of agreement +/- 0.61 degrees C (2SD)), and tympanic measurement had a bias of 0.021 degrees C (+/- 0.80 degrees C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r = 0.95, p < 0.0001) and also for tympanic versus bladder temperature (r = 0.96, p < 0.0001). CONCLUSIONS: That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring. PMID- 20581386 TI - The impact of an emergency telephone consultation service on the use of ambulances in Tokyo. AB - INTRODUCTION: The increasing demands made on emergency ambulance services contribute to inefficient, clinically inappropriate health care, and may delay the provision of emergency care to life-threatening cases. The hypothesis of this study was that the activity for the first year of operation of an emergency telephone consultation service contributed to a reduction in ambulance use in non urgent cases and a decrease in the cost associated with despatching ambulances. METHODS: The numbers of ambulance use and the emergency hospitalisation of ambulance cases were compared before and after the introduction of the Tokyo Emergency Telephone Consultation Centre (the #7119 centre). Public awareness of the #7119 centre in each region of Tokyo and the cost related to despatching ambulances were also investigated. RESULTS: A total of 26,138 consultations was performed in the initial year. Compared with the previous year, the number of ambulance uses per 1 million people decreased (before 46,846, after 44,689, p<0.0001). The emergency hospitalisation rate (EHR) of ambulance cases increased significantly because of the decreased proportion of non-urgent cases (before 36.5%, after 37.8%, p<0.0001). There was a statistical correlation between the awareness rate in each region and the change of after-hours EHR in adults (R=0.333, p=0.025). The total cost related to despatching ambulances was reduced by approximately Y678,000,000 (L4,520,000) in the initial year. CONCLUSION: To date, the emergency telephone consultation service has contributed to the appropriate use of ambulances and a reduction of its cost in Tokyo. PMID- 20581387 TI - National swine flu adult assessment guidelines: retrospective validation of objective criteria in three proxy datasets. AB - OBJECTIVES: To validate the objective criteria in the Department of Health Adult Swine Flu Assessment Tool against proxy datasets for pandemic influenza. DESIGN: Comparative validation study with 3 datasets. SETTING: Urban Emergency Department (group 1) and prehospital care (groups 2 and 3). PARTICIPANTS: Adults with community-acquired pneumonia (group 1, n=281), shortness of breath (group 2, n=211) or any respiratory diagnosis (group 3, n=300). OUTCOME MEASURES: Hospital admission (group 1), hospital admission or intravenous therapy (group 2) and transfer to emergency department (group 3). RESULTS: Sensitivity and specificity of the tool were 0.73 (95% CI 0.67 to 0.8) and 0.83 (0.72 to 0.9) in group 1, 0.64 (0.55 to 0.71) and 0.63 (0.52 to 0.73) in group 2 and 0.84 (0.75 to 0.9) and 0.55 (0.48 to 0.62) in group 3. Analysis of individual components of the tool and a summative score is presented. CONCLUSIONS: The objective criteria of the proposed DH assessment tool do not perform particularly well in predicting relevant clinical outcomes in feasible proxy conditions for pandemic influenza. PMID- 20581388 TI - No relationship between measures of clinical efficiency and teaching effectiveness for emergency medicine faculty. AB - OBJECTIVES: Emergency medicine (EM) doctors affiliated with academic institutions experience professional tension between providing excellent, timely care for patients and high-quality bedside instruction for residents and medical students. The goal of this study was to assess the relationship between measures of faculty clinical efficiency and teaching effectiveness. METHODS: This was a retrospective review of data from a single academic institution with an annual census of 55,000. Faculty clinical efficiency was measured by two variables: the relative value unit (RVU)/h ratio and average 'door to discharge' time. Teaching effectiveness was estimated by determining the average 'overall teaching' scores derived from anonymous EM resident and senior medical student evaluations. Relationships were assessed using the Spearman's correlation coefficient. RESULTS: There was no statistically significant relationship (p>0.050) between measures of faculty clinical efficiency and teaching effectiveness. CONCLUSION: These data replicate previous findings that clinical productivity has no correlation with teaching effectiveness for emergency medicine faculty doctors. PMID- 20581389 TI - Effect of clinician designation on emergency department fast track performance. AB - OBJECTIVE: To examine the effect of clinician designation on emergency department (ED) fast track performance. DESIGN AND SETTING: A retrospective audit of patients managed in the fast track area of an ED in metropolitan Melbourne, Australia. PARTICIPANTS: Patients triaged to ED fast track from 1 January 2008 to 31 December 2008 (n=8714). MAIN OUTCOME MEASURES: Waiting times in relation to Australasian triage scale (ATS) recommendations and ED length of stay (LOS) for non-admitted patients were examined for each clinician group. RESULTS: Compliance with ATS waiting time recommendations was highest (82.5%) for emergency nurse practitioners/candidates and lowest (48.2%) for junior medical officers. Median ED LOS was less than 3 h for non-admitted patients, and 85.8% of non-admitted fast track patients (n=6278) left the ED within 4 h. Patients managed by emergency nurse practitioners/candidates had the shortest ED LOS (median 1.7 h) and patients managed by junior medical officers and locum medical officers the longest ED LOS (median 2.7 h) (chi(2)=498.539, df=6, p<0.001). CONCLUSIONS: Clinician designation does impact on waiting times and, to a lesser extent, ED LOS for patients managed in ED fast track systems. Future research should focus on obtaining a better understanding of the relationship between clinician expertise, time-based performance measures and quality of care indicators. PMID- 20581390 TI - The role of health and non-health-related factors in repeat emergency department visits in an elderly urban population. AB - INTRODUCTION: Patients aged 65 years or older account for a growing proportion of emergency department (ED) repeat attendances. This study aimed to identify health and non-health factors associated with repeat ED attendance, defined as one or more visits in the previous 6 months in patients aged 65 years or older, and to examine the interaction between social and health factors. METHODS: 306 patients were interviewed. Demographic, socioeconomic, physical, mental health and post-ED referrals were examined. Logistic regression was used to identify factors independently associated with a repeat ED visit, OR and 95% CI are presented. Log likelihood ratio tests were used to test for interactions. RESULTS: ED revisits were reported by 37% of this elderly population. Independent risk factors for a repeat ED visit were previous hospital admission OR 3.78 (95% CI 2.53 to 5.65), anxiety OR 1.13 (95% CI 1.04 to 1.22), being part of a vulnerable social network OR 2.32 (95% CI 1.12 to 4.81), whereas a unit increase in physical inability as measured by the Nottingham Health Profile had a week association OR 1.01 (95% CI 1.00 to 1.02). There were no significant interactions between social networks and the other health-related variables (p>0.05). In patients directly discharged from ED, 48% (71/148) had no documented referrals made to community services, of which 18% (27/148) were repeat ED attendees. CONCLUSION: ED act as an important safety net for older people regardless of economic or demographic backgrounds. Appropriate assessment and referral are an essential part of this safety role. PMID- 20581391 TI - Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. AB - BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either sirolimus (target dose, 2 mg daily) or standard care. All patients had an estimated creatinine clearance of at least 70 ml per minute. Serial magnetic resonance imaging was performed to measure the volume of polycystic kidneys. The primary outcome was total kidney volume at 18 months on blinded assessment. Secondary outcomes were the glomerular filtration rate and urinary albumin excretion rate at 18 months. RESULTS: At randomization, the median total kidney volume was 907 cm3 (interquartile range, 577 to 1330) in the sirolimus group and 1003 cm3 (interquartile range, 574 to 1422) in the control group. The median increase over the 18-month period was 99 cm3 (interquartile range, 43 to 173) in the sirolimus group and 97 cm3 (interquartile range, 37 to 181) in the control group. At 18 months, the median total kidney volume in the sirolimus group was 102% of that in the control group (95% confidence interval, 99 to 105; P=0.26). The glomerular filtration rate did not differ significantly between the two groups; however, the urinary albumin excretion rate was higher in the sirolimus group. CONCLUSIONS: In adults with ADPKD and early chronic kidney disease, 18 months of treatment with sirolimus did not halt polycystic kidney growth. (Funded by Wyeth and others; ClinicalTrials.gov number, NCT00346918.) PMID- 20581392 TI - Everolimus in patients with autosomal dominant polycystic kidney disease. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive hereditary disorder that usually leads to end-stage renal disease. Although the underlying gene mutations were identified several years ago, efficacious therapy to curtail cyst growth and prevent renal failure is not available. Experimental and observational studies suggest that the mammalian target of rapamycin (mTOR) pathway plays a critical role in cyst growth. METHODS: In this 2-year, double-blind trial, we randomly assigned 433 patients with ADPKD to receive either placebo or the mTOR inhibitor everolimus. The primary outcome was the change in total kidney volume, as measured on magnetic resonance imaging, at 12 and 24 months. RESULTS: Total kidney volume increased between baseline and 1 year by 102 ml in the everolimus group, versus 157 ml in the placebo group (P=0.02) and between baseline and 2 years by 230 ml and 301 ml, respectively (P=0.06). Cyst volume increased by 76 ml in the everolimus group and 98 ml in the placebo group after 1 year (P=0.27) and by 181 ml and 215 ml, respectively, after 2 years (P=0.28). Parenchymal volume increased by 26 ml in the everolimus group and 62 ml in the placebo group after 1 year (P=0.003) and by 56 ml and 93 ml, respectively, after 2 years (P=0.11). The mean decrement in the estimated glomerular filtration rate after 24 months was 8.9 ml per minute per 1.73 m2 of body-surface area in the everolimus group versus 7.7 ml per minute in the placebo group (P=0.15). Drug-specific adverse events were more common in the everolimus group; the rate of infection was similar in the two groups. CONCLUSIONS: Within the 2-year study period,as compared with placebo, everolimus slowed the increase in total kidney volume of patients with ADPKD but did not slow the progression of renal impairment [corrected]. (Funded by Novartis; EudraCT number, 2006-001485 16; ClinicalTrials.gov number, NCT00414440.) PMID- 20581393 TI - mTOR inhibitors in polycystic kidney disease. PMID- 20581394 TI - Measurement of motivations for and against sexual behavior. AB - A multidimensional measure assessing distinct motivations for and against sex was shown to be reliable, valid, and configurally invariant among incoming first-year college students. Three Motivations Against Sex Questionnaire subscales were developed to measure motivations against sexual behavior (Values, Health, Not Ready) to complement and extend a set of Sexual Motivations Scale-Revised subscales assessing motivations for sexual behavior (Intimacy, Enhancement, Coping). Participants were surveyed the summer prior to college (N = 1,653; 58.4% female). Exploratory factor analysis on a random one quarter of respondents supported the hypothesized factors. Multigroup confirmatory factor analysis demonstrated good overall fit to the data and configural invariance across gender and ethnicity and across lifetime sexual experience. Motivations were associated with lifetime oral and penetrative sexual behaviors. This combined measure may be used for identifying motivations, predicting behaviors, and tailoring motivational interventions for sexual health among adolescents and young adults. PMID- 20581395 TI - Angiopoietin-like protein 3 inhibits lipoprotein lipase activity through enhancing its cleavage by proprotein convertases. AB - Lipoprotein lipase (LPL)-mediated lipolysis of triglycerides is the first and rate-limiting step in chylomicron/very low density lipoprotein clearance at the luminal surface of the capillaries. Angiopoietin-like protein 3 (ANGPTL3) is shown to inhibit LPL activity and plays important roles in modulating lipoprotein metabolism in vivo. However, the mechanism by which it inhibits LPL activity remains poorly understood. Using cell-based analysis of the interaction between ANGPTL3, furin, proprotein convertase subtilisin/kexin type 5 (PCSK5), paired amino acid converting enzyme-4 (PACE4), and LPL, we demonstrated that the cleavage of LPL by proprotein convertases is an inactivation process, similar to that seen for endothelial lipase cleavage. At physiological concentrations and in the presence of cells, ANGPTL3 is a potent inhibitor of LPL. This action is due to the fact that ANGPTL3 can enhance LPL cleavage by endogenous furin and PACE4 but not by PCSK5. This effect is specific to LPL but not endothelial lipase. Both N- and C-terminal domains of LPL are required for ANGPTL3-enhanced cleavage, and the N-terminal domain of ANGPTL3 is sufficient to exert its effect on LPL cleavage. Moreover, ANGPTL3 enhances LPL cleavage in the presence of either heparan sulfate proteoglycans or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1). By enhancing LPL cleavage, ANGPTL3 dissociates LPL from the cell surface, inhibiting both the catalytic and noncatalytic functions of LPL. Taken together, our data provide a molecular connection between ANGPTL3, LPL, and proprotein convertases, which may represent a rapid signal communication among different metabolically active tissues to maintain energy homeostasis. These novel findings provide a new paradigm of specific protease-substrate interaction and further improve our knowledge of LPL biology. PMID- 20581397 TI - Keeping nursing research afloat in a sinking economy. PMID- 20581398 TI - A PDA intervention to sustain smoking cessation in clients with socioeconomic vulnerability. AB - This article describes a pilot study to explore use of a personal digital assistant (PDA) to sustain smoking cessation after discharge in clients with socioeconomic vulnerability. The major aim is to describe technology acceptance (perceived ease of use, usefulness, and attitude), portability, technical difficulty, satisfaction, and use time. The sample includes 31 medical surgical clients with average age of 47.35 (+/-13.3), average household income of $13,629 (+/-8,204), average number in the household of 2.67 (+/-2.22), and average education of 11th grade. The results demonstrate mean use time of 9.28 (+/-3.23) hr, or about 1 hr over 8 weeks. Technology acceptance responses indicate the PDA is viewed as useful to the task of smoking cessation but is not perceived as easy to use. The most beneficial aspect is the portability. There are benefits to a PDA smoking cessation intervention but more study is needed before it can be used in practice. PMID- 20581396 TI - Disruption of protein kinase A localization using a trans-activator of transcription (TAT)-conjugated A-kinase-anchoring peptide reduces cardiac function. AB - Localization of protein kinase A (PKA) via A-kinase-anchoring proteins (AKAPs) is important for cAMP responsiveness in many cellular systems, and evidence suggests that AKAPs play an important role in cardiac signaling. To test the importance of AKAP-mediated targeting of PKA on cardiac function, we designed a cell-permeable peptide, which we termed trans-activator of transcription (TAT)-AKAD for TAT conjugated A-kinase-anchoring disruptor, using the PKA binding region of AKAP10 and tested the effects of this peptide in isolated cardiac myocytes and in Langendorff-perfused mouse hearts. We initially validated TAT-AKAD as a PKA localization inhibitor in cardiac myocytes by the use of confocal microscopy and cellular fractionation to show that treatment with the peptide disrupts type I and type II PKA regulatory subunits. Knockdown of PKA activity was demonstrated by decrease in phosphorylation of phospholamban and troponin I after beta adrenergic stimulation in isolated myocytes. Treatment with TAT-AKAD reduced myocyte shortening and rates of contraction and relaxation. Injection of TAT-AKAD (1 microM), but not scrambled control peptide, into the coronary circulation of isolated perfused hearts rapidly (<1 min) and reversibly decreased heart rate and peak left ventricular developed pressure. TAT-AKAD also had a pronounced effect on developed pressure (-dP/dt), consistent with a delayed relaxation of the heart. The effects of TAT-AKAD on heart rate and contractility persisted in hearts pretreated with isoproterenol. Disruption of PKA localization with TAT AKAD thus had negative effects on chronotropy, inotropy, and lusitropy, thereby indicating a key role for AKAP-targeted PKA in control of heart rate and contractile function. PMID- 20581399 TI - Forearm and upper-arm oscillometric blood pressure comparison in acutely ill adults. AB - When patients' upper arms are not accessible and/or when cuffs do not fit large upper arms, the forearm site is often used for blood pressure (BP) measurement. The purpose of this study is to compare forearm and upper-arm BPs in 70 acutely ill adults, admitted to a community hospital's 14-bed ICU. Using Philips oscillometric monitors, three repeated measures of forearm and upper-arm BPs are obtained with head of bed flat and with head of bed elevated at 30 degrees. Arms are resting on the bed. Paired t tests show statistically significant differences in systolic BPs, diastolic BPs, and mean arterial pressures in the supine and head-elevated positions. Bland-Altman analyses indicate that forearm and upper arm oscillometric BPs are not interchangeable in acutely ill adults. PMID- 20581400 TI - EGM: encapsulated gene-by-gene matching to identify gene orthologs and homologous segments in genomes. AB - MOTIVATION: Identification of functionally equivalent genes in different species is essential to understand the evolution of biological pathways and processes. At the same time, identification of strings of conserved orthologous genes helps identify complex genomic rearrangements across different organisms. Such an insight is particularly useful, for example, in the transfer of experimental results between different experimental systems such as Drosophila and mammals. RESULTS: Here, we describe the Encapsulated Gene-by-gene Matching (EGM) approach, a method that employs a graph matching strategy to identify gene orthologs and conserved gene segments. Given a pair of genomes, EGM constructs a global gene match for all genes taking into account gene context and family information. The Hungarian method for identifying the maximum weight matching in bipartite graphs is employed, where the resulting matching reveals one-to-one correspondences between nodes (genes) in a manner that maximizes the gene similarity and context. CONCLUSION: We tested our approach by performing several comparisons including a detailed Human versus Mouse genome mapping. We find that the algorithm is robust and sensitive in detecting orthologs and conserved gene segments. EGM can sensitively detect rearrangements within large and small chromosomal segments. The EGM tool is fully automated and easy to use compared to other more complex methods that also require extensive manual intervention and input. AVAILABILITY: The EGM software, Supplementary information and other tools are available online from http://vbc.med.monash.edu.au/ approximately kmahmood/EGM. PMID- 20581401 TI - Deciphering subcellular processes in live imaging datasets via dynamic probabilistic networks. AB - MOTIVATION: Designing mathematical tools that can formally describe the dynamics of complex intracellular processes remains a challenge. Live cell imaging reveals changes in the cellular states, but current simple approaches extract only minimal information of a static snapshot. RESULTS: We implemented a novel approach for analyzing organelle behavior in live cell imaging data based on hidden Markov models (HMMs) and showed that it can determine the number and evolution of distinct cellular states involved in a biological process. We analyzed insulin-mediated exocytosis of single Glut4-vesicles, a process critical for blood glucose homeostasis and impaired in type II diabetes, by using total internal reflection fluorescence microscopy (TIRFM). HMM analyses of movie sequences of living cells reveal that insulin controls spatial and temporal dynamics of exocytosis via the exocyst, a putative tethering protein complex. Our studies have validated the proof-of-principle of HMM for cellular imaging and provided direct evidence for the existence of complex spatial-temporal regulation of exocytosis in non-polarized cells. We independently confirmed insulin dependent spatial regulation by using static spatial statistics methods. CONCLUSION: We propose that HMM-based approach can be exploited in a wide avenue of cellular processes, especially those where the changes of cellular states in space and time may be highly complex and non-obvious, such as in cell polarization, signaling and developmental processes. PMID- 20581402 TI - Over-optimism in bioinformatics: an illustration. AB - MOTIVATION: In statistical bioinformatics research, different optimization mechanisms potentially lead to 'over-optimism' in published papers. So far, however, a systematic critical study concerning the various sources underlying this over-optimism is lacking. RESULTS: We present an empirical study on over optimism using high-dimensional classification as example. Specifically, we consider a 'promising' new classification algorithm, namely linear discriminant analysis incorporating prior knowledge on gene functional groups through an appropriate shrinkage of the within-group covariance matrix. While this approach yields poor results in terms of error rate, we quantitatively demonstrate that it can artificially seem superior to existing approaches if we 'fish for significance'. The investigated sources of over-optimism include the optimization of datasets, of settings, of competing methods and, most importantly, of the method's characteristics. We conclude that, if the improvement of a quantitative criterion such as the error rate is the main contribution of a paper, the superiority of new algorithms should always be demonstrated on independent validation data. AVAILABILITY: The R codes and relevant data can be downloaded from http://www.ibe.med.uni muenchen.de/organisation/mitarbeiter/020_professuren/boulesteix/overoptimism/, such that the study is completely reproducible. PMID- 20581403 TI - Images in emergency medicine. Wegener's granulomatosis: a rare presentation. PMID- 20581404 TI - Nasal foreign bodies in children: kissing it better. AB - OBJECTIVE: To evaluate the use, success rate and time in the paediatric emergency department when employing the kissing technique to remove nasal foreign bodies from children. METHODS: The present work was a retrospective case note review for children attending with a nasal foreign body over a 15-month period. RESULTS: In all, 116 children had a confirmed nasal foreign body and 84 were treated by the kissing technique with a success rate of 48.8%. This group had lower rates of instrumentation (20.2% vs 53.1%) and general anaesthesia (11.9% vs 18.8%). The average time saved per patient who had the kissing technique attempted in the paediatric emergency department was 30.6 min. CONCLUSION: The kissing technique should be employed as a preferred technique to remove nasal foreign bodies in children. PMID- 20581405 TI - Crush pelvic injury in the Sichuan earthquake evaluated by multidetector CT scanning. AB - CT scanning is sensitive and specific for the identification of pelvic fractures and injury to the pelvic wall soft tissue and the pelvic cavity. Crush pelvic trauma in an earthquake can be identified by multidetector CT scanning. PMID- 20581406 TI - Acute cerebellar ataxia in childhood: initial approach in the emergency department. AB - Acute childhood ataxia is a relatively common presenting complaint in paediatric emergency settings. Because life-threatening causes of pure ataxia are rare in children, an approach in a stepwise fashion is recommended. Acute cerebellar ataxia is the most common cause of childhood ataxia, accounting for about 30-50% of all cases. Varicella is the most commonly associated virus. Post-varicella acute cerebellar ataxia (PVACA) is the most common neurological complication of varicella, occurring about once in 4000 varicella cases among children younger than 15 years of age, even in the postvaccine era. We describe an unimmunised child with PVACA to remind emergency physicians about its autoimmune pathogenesis. We also briefly discuss current controversies about the diagnostic approach and management. PMID- 20581407 TI - Imaging patients with renal colic: a comparative analysis of the impact of non contrast helical computed tomography versus intravenous pyelography on the speed of patient processing in the Emergency Department. AB - INTRODUCTION: Non-contrast helical CT (NHCT) became the procedure of choice for investigating Emergency Department (ED) patients presenting with suspected renal colic at Beaumont Hospital, Dublin, in 2008. The impact of NHCT on waiting times and patient management was compared with intravenous pyelography (IVP). METHODS: A retrospective, comparative cohort analysis of 95 patients who had IVP and 109 patients who had NHCT was performed. Length of ED stay from time of scan ordering to referral or discharge was analysed relative to time of day and scan result. RESULTS: Patients having NHCT who attended between 00:00-08:00 h, had a twofold longer length of stay than those who had IVP between the same hours (median 7.07 h vs 3.03 h, p=0.0294). The length of ED stay for patients attending between 08:00 and 24:00 h was similar in both groups. The presence of urolithiasis did not impact on length of stay. A significant alternate/incidental diagnosis was reported in 28 patients having NHCT, of which 12 were cancerous growths. CONCLUSION: NHCT allows for the detection of incidental/alternate diagnoses that may not be otherwise detected in patients with renal colic. Compared to IVP, NHCT has not impacted positively on the speed of patient processing in the ED under study. For patients presenting after midnight, it is associated with over a twofold longer length of stay from the time of scan ordering to referral or discharge. This leads to prolonged patient stays in the ED, and as such contributes to overcrowding. PMID- 20581408 TI - Barriers to incident notification in a regional prehospital setting. AB - BACKGROUND: The identification and monitoring of critical incidents or adverse events and error reporting is a relatively new area of study in the prehospital setting. In 2005, we commenced a prospective descriptive study of the implementation of a Critical Incident Monitoring process in a rural/regional pre hospital setting. The objective of the project was to describe the nature and incidence of errors detected in the management of prehospital trauma with the ultimate aim of identifying processes to reduce or mitigate such incidents. This paper describes the barriers to reporting critical incidents identified during the 3-year study. METHOD: This study used a qualitative approach involving the triangulation of a number of ethnographic methodologies, including unscripted focus groups, informal interviews and qualitative aspects of surveys utilised in a broader research project. Prevailing themes were fed back to participants in an iterative process to further explore perceptions and beliefs regarding these concepts. The final analysis of themes is descriptively presented. RESULTS: A number of barriers were identified and categorised into seven themes. These themes were; Burden of reporting, fear of disciplinary action, fear of potential litigation, fear of breaches of confidentiality and fear of embarrassment, concern that 'nothing would change' even if the incident was reported, lack of familiarity with process and impact of 'blame culture'. CONCLUSION: There are numerous barriers to reporting critical incidents. One of the key approaches which may alleviate many of the barriers to reporting is shifting to a systems based focus rather than an individual 'shame and blame' approach. The underlying barriers lie in the culture of the profession, and appear consistent across other health care disciplines. PMID- 20581411 TI - Posterior cerebral artery dissecting aneurysm: another cause of perimesencephalic pattern of subarachnoid haemorrhage. PMID- 20581410 TI - Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. AB - BACKGROUND: An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. METHODS: Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. RESULTS: Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. CONCLUSIONS: Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling. PMID- 20581409 TI - Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal. AB - The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting beta agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6-12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7-10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy. PMID- 20581412 TI - 'Hemispherical asymmetry in the Meyer's Loop': a prospective study of visual field deficits in 105 cases undergoing anterior temporal lobe resection for epilepsy. AB - OBJECTIVES: Visual-field deficits following temporal lobe surgery have been reported in the literature. In this prospective study, the authors analyse their experience of visual-field deficits in 105 consecutive cases undergoing temporal lobe surgery performed by a single surgeon, with particular consideration to the laterality of the deficit and its functional implications. METHODS: 105 consecutive patients undergoing an anterior temporal lobe resection for epilepsy, between March 1998 and June 2004, were selected. The patient population had a mean age of 35 years (range 19-60 years); 53 had a left-sided resection and 52 a right-sided resection. 91 patients had mesial temporal sclerosis, three gangliogliomas, four dysembryoplastic neuroepithelial tumours (DNETs), two neurocytomas and two cavernomas, and in three cases the histology was inconclusive. Pre- and postoperative visual-field tests were obtained using the Humphrey Esterman binocular functional test for all cases. The test was set to stimulus white III, with a single intensity of 10 DB on the background of 31.5 ASB for all patients. A minimum follow-up period of 12 months postsurgery was employed. Postoperative MRI scans were carried out on all patients. 60 scans were randomly selected, and the extent of temporal lobe resection calculated manually for each. RESULTS: Of the 105 cases, 16 patients had a visual-field deficit postoperatively which was not present preoperatively: 12 following a left and four following a right-sided resection. The OR for incurring a postoperative visual-field defect following left versus right-sided surgery was 3.51 (95% CI 1.05 to 11.73, p=0.04). In four patients, the deficit was severe enough to preclude them from driving in the UK (three left- and one right-sided resection). There was no association between the extent of tissue resection and the incidence of postoperative visual-field deficits. CONCLUSIONS: This study suggests left /right-hemispherical asymmetry in the Geniculocalcarine tracts with field deficits being 3.5 times more likely following left-sided anterior temporal lobe resections compared with right-sided resections. This has significant implications on counselling patients for these procedures. MR tractography may provide an anatomical substrate for these clinical findings, perhaps revealing a more anterior course of the optic radiations within the temporal lobe in one hemisphere versus the other. PMID- 20581413 TI - Marked reduction of tremor in essential tremor after putaminal infarct. PMID- 20581414 TI - Neurological picture: Cranial neuropathy in the blue rubber bleb nevus syndrome. PMID- 20581415 TI - Radiculomyelitis due to atypical tuberculous infection: 4 cases report. PMID- 20581416 TI - Neurological picture. Reversible eclamptic leucoencephalopathy syndrome with severe brainstem involvement without neurological signs. PMID- 20581417 TI - Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study. AB - OBJECTIVES: To study welding fume particles in relation to cardiovascular diseases. METHODS: In 1986, 10,059 male metal workers in 75 welding companies were sent a questionnaire about their welding experience and lifestyle (83.3% response rate). Of these, 5866 were available for analysis and had ever welded at baseline. Information on exposure to welding fumes after 1986 was obtained by individual linkage to the National Pension Fund. Lifelong exposure to welding fume particles was estimated from a job-exposure matrix based on more than 1000 welding-specific measures of fume particles. Hospital contacts for cardiovascular disease were obtained from the Danish National Patient Registry by individual linkage. The nine disease outcomes considered were acute myocardial infarct (AMI), angina pectoris, other acute ischaemic heart diseases, chronic ischaemic heart disease (CHD), cardiac arrythmias, cardiac arrest, heart failure, cerebral infarct, arterial embolism and thrombosis. The cohort was followed up from baseline until the end of 2006. RESULTS: When the incidence of each of the nine cardiovascular outcomes among welders was compared with 5-year age- and calendar year-specific male national rates, the number of observed cases significantly exceeded that expected for AMI (standardised incidence ratio, 95% CI) (1.12, 1.01 to 1.24), angina pectoris (1.11, 1.01 to 1.22), CHD (1.17, 1.05 to 1.31) and cerebral infarct (1.24, 1.06 to 1.44). Internal comparisons of the cohort with adjustment for tobacco smoking, alcohol and hypertension medicines showed a significantly increasing hazard rate ratio for CHD and non-significant increases for AMI, angina pectoris and cerebral infarct with increasing exposure to particles. CONCLUSIONS: This study supports the hypothesis that exposure to welding processed particles increases the risk for cardiovascular disease. PMID- 20581418 TI - Optimising sampling strategies: components of low-back EMG variability in five heavy industries. AB - BACKGROUND: Direct/ measurement of work activities is costly, so researchers need to distribute resources efficiently to elucidate the relationships between exposures and back injury. METHODS: This study used data from full-shift electromyography (EMG; N=133) to develop three exposure metrics: mean, 90th percentile and cumulative EMG. For each metric, the components of variance were calculated between- and within-subject, and between-group for four different grouping schemes: grouping by industry (construction, forestry, transportation, warehousing and wood products), by company, by job and by quintiles based on exposures ranked by jobs within industries. Attenuation and precision of simulated exposure-response relationships were calculated for each grouping scheme to determine efficient sampling strategies. RESULTS: As expected, grouping based on exposure quintiles had the highest between-group variances and lowest attenuation, demonstrating the lowest possible attenuation with this data. CONCLUSION: There is potential for grouping schemes to reduce attenuation, but precision losses should be considered and whenever possible empirical data should be employed to select potential exposure grouping schemes. PMID- 20581419 TI - Occupational exposures and risk of acoustic neuroma. AB - OBJECTIVES: Acoustic neuroma is a benign tumour accounting for approximately 6 10% of all intracranial tumours and occurs mainly in patients aged >=50 years. Our aim was to investigate a wide range of occupational exposures, individual occupational titles and socioeconomic status (SES) as potential risk factors for acoustic neuroma. METHODS: We conducted a population-based case-control study of 793 acoustic neuroma cases identified through the Swedish Cancer Registry and 101,762 randomly selected controls. Information on SES and occupation was obtained from censuses and linked to job-exposure matrices. Logistic regression was used to estimate ORs and calculate 95% CIs. RESULTS: An increased OR was seen for mercury exposure <10 years before the reference year (OR 2.9; 95% CI 1.2 to 6.8), and a more modest association for benzene exposure (OR 1.8; 95% CI: 1.0 to 3.2) >=10 years before the reference year. We observed a threefold increased risk for females working as tailors and dressmakers >=10 years before the reference year, and a more than threefold significantly elevated OR for those working as truck and conveyor operators <10 years before the reference year. We found no convincing evidence that SES is related to disease development. CONCLUSION: We observed an increased risk of acoustic neuroma associated with occupational exposure to mercury, benzene and textile dust. Men working as truck and conveyor operators <10 years before the reference year had the highest increased risk of acoustic neuroma, but it is unclear what in those occupations might contribute to disease development. Our study also suggested an association between acoustic neuroma and being a class teacher or policeman. However, these findings should be further investigated to exclude the possibility of detection bias. PMID- 20581421 TI - The initiation of renal-replacement therapy--just-in-time delivery. PMID- 20581420 TI - A school-based intervention for diabetes risk reduction. AB - BACKGROUND: We examined the effects of a multicomponent, school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes. METHODS: Using a cluster design, we randomly assigned 42 schools to either a multicomponent school-based intervention (21 schools) or assessment only (control, 21 schools). A total of 4603 students participated (mean [+/- SD] age, 11.3 [+/- 0.6 years; 54.2% Hispanic and 18.0% black; 52.7% girls). At the beginning of 6th grade and the end of 8th grade, students underwent measurements of body-mass index (BMI), waist circumference, and fasting glucose and insulin levels. RESULTS: There was a decrease in the primary outcome--the combined prevalence of overweight and obesity--in both the intervention and control schools, with no significant difference between the school groups. The intervention schools had greater reductions in the secondary outcomes of BMI z score, percentage of students with waist circumference at or above the 90th percentile, fasting insulin levels (P=0.04 for all comparisons), and prevalence of obesity (P=0.05). Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline. Less than 3% of the students who were screened had an adverse event; the proportions were nearly equivalent in the intervention and control schools. CONCLUSIONS: Our comprehensive school-based program did not result in greater decreases in the combined prevalence of overweight and obesity than those that occurred in control schools. However, the intervention did result in significantly greater reductions in various indexes of adiposity. These changes may reduce the risk of childhood-onset type 2 diabetes. (Funded by the National Institutes of Health and the American Diabetes Association; ClinicalTrials.gov number, NCT00458029.) PMID- 20581423 TI - Acceptability of offering financial incentives to achieve medication adherence in patients with severe mental illness: a focus group study. AB - BACKGROUND: Offering financial incentives to achieve medication adherence in patients with severe mental illness is controversial. AIMS: To explore the views of different stakeholders on the ethical acceptability of the practice. METHOD: Focus group study consisting of 25 groups with different stakeholders. RESULTS: Eleven themes dominated the discussions and fell into four categories: (1) 'wider concerns', including the value of medication, source of funding, how patients would use the money, and a presumed government agenda behind the idea; (2) 'problems requiring clear policies', comprising of practicalities and assurance that incentives are only one part of a tool kit; (3) 'challenges for research and experience', including effectiveness, the possibility of perverse incentives, and impact on the therapeutic relationship; (4) 'inherent dilemmas' around fairness and potential coercion. CONCLUSIONS: The use of financial incentives is likely to raise similar concerns in most stakeholders, only some of which can be addressed by empirical research and clear policies. PMID- 20581424 TI - Prognostic significance of acute pain preceding out-of-hospital cardiac arrest. AB - BACKGROUND: Sudden loss of consciousness (LOC) and chest pain are common manifestations of out-of-hospital cardiac arrest (OHCA). History of acute pain may be helpful in estimating aetiology and prognosis of OHCA victims. The objective of this study was to evaluate the relationship between acute pain at various locations preceding collapse and outcome. METHODS: Clinical data of 250 witnessed, non-traumatic OHCA victims were reviewed, and the incidence of pain based on anatomical distribution was documented. The focus was on identifying the difference between those collapsing with LOC alone and those collapsing with chest pain (CP). Clinical variables predictive of survival were identified using a logistic regression model. RESULTS: Among the 250 victims, 55.2% collapsed with LOC alone. The incidence of acute pain was: 28.0% for CP, 3.2% for headache, 2.8% for abdominal pain and 2.4% for back pain. The overall 6-month survival rate was 7.2%. The LOC group had a significantly higher return of spontaneous circulation (ROSC) rate compared with the CP group (48.6% vs 31.4%, p<0.05). The rate was elevated in the LOC group; however, only when the initial rhythm was non shockable. There was no significant intergroup difference in the survival rate. Initial shockable rhythm positively and history of cardiovascular diseases negatively predicted survival. None of the victims in the headache, abdominal pain or back pain groups survived. CONCLUSION: The LOC group's seemingly higher ROSC rate may be due to its aetiological heterogeneity. Complaint of a headache, abdominal pain or back pain in OHCA victims carries a poor prognosis. PMID- 20581425 TI - Performance of low-voltage STEM/TEM with delta corrector and cold field emission gun. AB - To reduce radiation damage caused by the electron beam and to obtain high contrast images of specimens, we have developed a highly stabilized transmission electron microscope equipped with a cold field emission gun and spherical aberration correctors for image- and probe-forming systems, which operates at lower acceleration voltages than conventional transmission electron microscopes. A delta-type aberration corrector is designed to simultaneously compensate for third-order spherical aberration and fifth-order 6-fold astigmatism. Both were successfully compensated in both scanning transmission electron microscopy (STEM) and transmission electron microscopy (TEM) modes in the range 30-60 kV. The Fourier transforms of raw high-angle annular dark field (HAADF) images of a Si[110] sample revealed spots corresponding to lattice spacings of 111 and 96 pm at 30 and 60 kV, respectively, and those of raw TEM images of an amorphous Ge film with gold particles showed spots corresponding to spacings of 91 and 79 pm at 30 and 60 kV, respectively. Er@C(82)-doped single-walled carbon nanotubes, which are carbon-based samples, were successfully observed by HAADF-STEM imaging with an atomic-level resolution. PMID- 20581422 TI - A randomized, controlled trial of early versus late initiation of dialysis. AB - BACKGROUND: In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. METHODS: We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft-Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. RESULTS: Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). CONCLUSIONS: In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.) PMID- 20581426 TI - Who is exposed to smoke at home? A population-based cross-sectional survey in central Vietnam. PMID- 20581428 TI - Multiscale permutation entropy analysis of EEG recordings during sevoflurane anesthesia. AB - Electroencephalogram (EEG) monitoring of the effect of anesthetic drugs on the central nervous system has long been used in anesthesia research. Several methods based on nonlinear dynamics, such as permutation entropy (PE), have been proposed to analyze EEG series during anesthesia. However, these measures are still single scale based and may not completely describe the dynamical characteristics of complex EEG series. In this paper, a novel measure combining multiscale PE information, called CMSPE (composite multi-scale permutation entropy), was proposed for quantifying the anesthetic drug effect on EEG recordings during sevoflurane anesthesia. Three sets of simulated EEG series during awake, light and deep anesthesia were used to select the parameters for the multiscale PE analysis: embedding dimension m, lag tau and scales to be integrated into the CMSPE index. Then, the CMSPE index and raw single-scale PE index were applied to EEG recordings from 18 patients who received sevoflurane anesthesia. Pharmacokinetic/pharmacodynamic (PKPD) modeling was used to relate the measured EEG indices and the anesthetic drug concentration. Prediction probability (P(k)) statistics and correlation analysis with the response entropy (RE) index, derived from the spectral entropy (M-entropy module; GE Healthcare, Helsinki, Finland), were investigated to evaluate the effectiveness of the new proposed measure. It was found that raw single-scale PE was blind to subtle transitions between light and deep anesthesia, while the CMSPE index tracked these changes accurately. Around the time of loss of consciousness, CMSPE responded significantly more rapidly than the raw PE, with the absolute slopes of linearly fitted response versus time plots of 0.12 (0.09-0.15) and 0.10 (0.06-0.13), respectively. The prediction probability P(k) of 0.86 (0.85-0.88) and 0.85 (0.80-0.86) for CMSPE and raw PE indicated that the CMSPE index correlated well with the underlying anesthetic effect. The correlation coefficient for the comparison between the CMSPE index and RE index of 0.84 (0.80-0.88) was significantly higher than the raw PE index of 0.75 (0.66-0.84). The results show that the CMSPE outperforms the raw single-scale PE in reflecting the sevoflurane drug effect on the central nervous system. PMID- 20581429 TI - Reproductive responses to daily injections with porcine somatotropin before mating in gilts. AB - Litter size and progeny birth weights are lower in gilts than in sows. Somatotropin (ST) is an important regulator of ovulation, fetal growth and survival. We therefore investigated effects of pST treatment of gilts for two to four weeks before mating on ovulation rate, behavioural estrus, fetal growth and survival, litter size and birth weights. In Experiment One, gilts were injected with 0, 30, 60 or 90 ug pST/kg/day for 14 days commencing 7 days after first estrus. Reproductive tracts were collected and corpora lutea and follicle numbers counted 5.5 days after second estrus. Ovulation rate (P=0.031) and number of medium-sized follicles (P=0.059) correlated positively with pST dose. In Experiment Two, gilts were injected with 0, 12.5, 25 or 50 ug pST/kg/day for 21 days from first estrus, and mated at second estrus. Numbers of corpora lutea, follicles and fetuses were counted at day 31 of pregnancy. Numbers of medium follicles and ovary weights were positively related to pST dose. In Experiment Three, 31 week old (1(st) replicate) or 27 week old (2(nd) replicate) gilts were injected daily with 0 or 12.5 ug pST/kg/day until mating 25.9 +/- 0.6 days later, and delivered at term. Pre-mating pST increased total litter size in younger gilts in the 2(nd) replicate only (P<0.05). In conclusion, injecting gilts with pST before mating does not consistently alter ovulation rate, increases the number of medium follicles available for recruitment at the second mating after treatment and increases subsequent litter size in younger gilts. PMID- 20581427 TI - Quantifying the effects of promoting smokeless tobacco as a harm reduction strategy in the USA. AB - BACKGROUND: Snus (a form of smokeless tobacco) is less dangerous than cigarettes. Some health professionals argue that snus should be promoted as a component of a harm reduction strategy, while others oppose this approach. Major US tobacco companies (RJ Reynolds and Philip Morris) are marketing snus products as cigarette brand line extensions. The population effects of smokeless tobacco promotion will depend on the combined effects of changes in individual risk with population changes in tobacco use patterns. OBJECTIVE: To quantitatively evaluate the health impact of smokeless tobacco promotion as part of a harm reduction strategy in the US. METHODS: A Monte Carlo simulation of a decision tree model of tobacco initiation and use was used to estimate the health effects associated with five different patterns of increased smokeless tobacco use. RESULTS: With cigarette smoking having a health effect of 100, the base case scenario (based on current US prevalence rates) yields a total health effect of 24.2 (5% to 95% interval 21.7 to 26.5) and the aggressive smokeless promotion (less cigarette use and increased smokeless, health-concerned smokers switching to snus, smokers in smokefree environments switching to snus) was associated with a health effect of 30.4 (5% to 95% interval 25.9 to 35.2). The anticipated health effects for additional scenarios with lower rates of smokeless uptake also overlapped with the base case. CONCLUSIONS: Promoting smokeless tobacco as a safer alternative to cigarettes is unlikely to result in substantial health benefits at a population level. PMID- 20581430 TI - Elevation of adipsin, a complement activating factor, in the mouse placenta during spontaneous abortion. AB - The complement system is thought to be precisely regulated during pregnancy. We have examined specific gene profiles in mouse placentas causing spontaneous abortion and found notable up-regulation of adipsin, a complement activating factor. The aim of the present study was to determine the basic kinetics and localization of adipsin in the placenta and the difference in complement activity between normal placentas and placentas of abortuses. Normal and spontaneously absorbed implantation sites obtained from naturally-mated mouse uteri on days 10.5 and 14.5 of pregnancy were processed for histologic studies and protein purification. Adipsin immunoreaction was detected at the decidua basalis in normal placentas and additionally at the placental labyrinth in the absorbed placentas. The quantity of adipsin was increased in the absorbed placentas compared with the normal placentas. In concert with the increase in adipsin, the amounts of complement component 3 and degradation products were elevated and complemental activity was up-regulated in the absorbed placenta. These findings suggest that local expression of adipsin has a reproductive effect at the feto maternal interface and possibly plays a role in spontaneous abortion. PMID- 20581431 TI - Occlusal disharmony in mice transiently activates microglia in hippocampal CA1 region but not in dentate gyrus. AB - Occlusal disharmony is induced by various conditions such as the loss of teeth and inappropriate vertical dimension of crowns, bridges, or dentures. Occlusal disharmony sometimes causes indefinite complaint syndromes, which may be associated with astrocytic hypertrophy and the reduction of numbers of neuronal somata and their dendritic spines in the hippocampus. Microglia monitors the condition of neurons and responds to their degeneration accompanying with astrocytes. However, the effect of occlusal disharmony on the microglia has not yet been investigated. We artificially increased the occlusal vertical dimension by placing dental resin on the upper molars in mice and immunohistochemically investigated the effects of the increase in the vertical dimension on microglia of the hippocampal formation using an antibody against ionized calcium-binding adaptor molecule 1 (Iba-1), a marker protein for microglia. We measured the area occupied by Iba-1-immunoreactive microglia in the hippocampal CA1 region and dentate gyrus 1, 3, and 5 days after increasing the vertical dimension, and compared it with that of control mice. The hippocampal CA1 region contains vulnerable neurons and the dentate gyrus durable neurons. We found that the areas occupied by microglia in the hippocampal CA1 region increased, with the peak on the third day after increasing the vertical dimension, and it gradually declined by the fifth post-operative day. However, such an increase of the area occupied by microglia was not seen in the dentate gyrus. In conclusion, abnormal mastication may activate microglia in the area harboring vulnerable neurons, but not in the area harboring durable neurons. PMID- 20581432 TI - The potential role of colesevelam in the management of prediabetes and type 2 diabetes mellitus. AB - Successful management of prediabetes and type 2 diabetes mellitus (T2DM) requires a multifaceted, multidisciplinary approach that involves patient education and support, lifestyle modification, and appropriate use of pharmacologic interventions with frequent monitoring and adjustment to ensure that target goals for hyperglycemia, dyslipidemia, and hypertension are achieved and maintained. Studies have shown that the bile acid sequestrant colesevelam HCl reduces hemoglobin A1c and low-density lipoprotein-cholesterol levels in patients with prediabetes and T2DM. This article briefly reviews current treatment guidelines for patients with prediabetes and T2DM and the potential role of colesevelam in the management of prediabetes and T2DM with oral antidiabetes agents. PMID- 20581433 TI - Muscle stem cells and reversible quiescence: the role of sprouty. AB - Quiescence is a critical determinant for sustained stem cell function throughout life. Disruption of cellular quiescence leads to loss of the stem cell pool and impaired tissue repair. In adult skeletal muscle, Pax7(+) satellite cells (the muscle stem cells) are capable of self-renewal and differentiation in their endogenous environment during repair. In response to muscle injury, Pax7(+) satellite cells enter the cell cycle; subpopulation returns to quiescence to fully replenish the satellite cell pool while others contribute to myofiber repair. We demonstrate that Sprouty1 (Spry1), an inhibitor of receptor tyrosine kinase signaling is required for the return to quiescence of the self-renewing Pax7(+) satellite cell pool during repair. The temporal regulation of Spry1 expression during repair and its functional requirement in a subpopulation of cycling Pax7(+) cells during repair ensure that tissue regeneration and re establishment of the dormant stem cell pool are coordinated. PMID- 20581434 TI - Medulloblastoma: a disease with disorganized developmental signaling cascades. AB - Sonic Hedgehog, Wnt and PI3K/Akt are three developmental signalling cascades that all have crucial functions during normal brain development. The activation of one or several of these cascades is also found in the majority of medulloblastoma, the most common pediatric malignant tumor of the central nervous system. The aberrant expression of key molecules in developmental signalling pathways or inhibition of the activity of proteins regulating the activity of these cascades is important for medulloblastoma proliferation and survival. These developmental signal transduction pathways transfer signals from the cell membrane to transcription factors in the nucleus, resulting in an altered gene expression. Molecular cross-talks between these developmental cascades have been described in several cancers and may have important functions in tumorigenesis. One common kinase for these three signalling cascades is GSK-3beta, which seems to be the glue that links these cascades together. Medulloblastoma cells display many characteristics that are interrelated to the progenitor cells of the embryonic brain where these developmental cascades are essential for proper development. Hence, understanding the relationship between normal brain development and medulloblastoma molecular pathogenesis is essential for more efficient, less toxic tailored therapies to be developed and implemented. PMID- 20581435 TI - More microtubule severing proteins: more microtubules. PMID- 20581436 TI - ATM engages the TSC2/mTORC1 signaling node to regulate autophagy. AB - The link between reactive oxygen species (ROS) and induction of autophagy has been well documented, but the molecular mechanisms regulating this phenomenon are only beginning to be elucidated. Autophagy is now being appreciated as an integral part of the cellular response to many diverse types of cellular stresses including nutrient deprivation, hypoxia, oxidative stress, and DNA damage, and likely the mechanism(s) for each type of stress vary considerably. The cellular outcome of inducing autophagy in response to stress is also quite complex, and depends on many factors including cellular context, type and magnitude of stress. PMID- 20581437 TI - Need radioprotection? A MEPE/OF45 mimetic may do the job. PMID- 20581438 TI - Guarding genome integrity in stem cells. PMID- 20581440 TI - Towards defining a role for DDK in replication fork stabilization and/or recovery. PMID- 20581439 TI - Lamin A precursor induces barrier-to-autointegration factor nuclear localization. AB - Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects. PMID- 20581441 TI - Filling out the gaps is the hardest (yet rewarding) task: the genome-wide collection of the fission yeast deletion mutants is near completion. PMID- 20581442 TI - Mammosphere-forming cells from breast cancer cell lines as a tool for the identification of CSC-like- and early progenitor-targeting drugs. AB - Here we show that a subpopulation of MCF-7 breast cancer cells which stains pale to Toluidine Blue (Light Cells- LCs), is endowed with features of CSCs. LCs give rise to self-renewing mammospheres and express typical CSC markers; moreover this subpopulation is chemoresistant and highly tumorigenic in vivo. LCs can be identified in several other breast cancer cell lines, irrespectively of their histological origin (luminal vs. mesenchymal vs. basal) and represent an heterogeneous cell population composed mainly of CSC-like and early progenitor cells. By a limited in vitro drug screening assay, we identify compounds which can specifically interfere with the viability of LCs from multiple breast cancer cell lines. Analysis of the Sphere-Forming Efficiency (SFE) and of the distribution of ALDH(bright) cells within the treated cell lines suggest that one of the identified compounds acts in vitro by modulating the CSC phenotype. Interestingly, a subset of the identified compounds is known to affect directly or indirectly the NFkappaB pathway which is emerging as an important modulator of CSC proliferation and chemoresistance. PMID- 20581443 TI - The cell cycle and pluripotency: Is there a direct link? PMID- 20581444 TI - Checks and balances: E2F-microRNA crosstalk in cancer control. AB - Extensive research on the E2F transcription factor family over the past decades has led to numerous insights that revealed the involvement of particularly E2F1 not only in proliferation and tumorigenesis but also in apoptosis and differentiation. Latest reports uncovered an essential role for oncogene signaling in regulating the balance of these events on the road to malignancy. Alterations in E2F functions coincide with poor prognosis in cancers, emphasizing their importance for the clinical cancer phenotype. An intriguing addition to the understanding of E2F crosstalks was the finding that their activity can be regulated by micro-RNAs (miRNAs) whose dysregulation has been implicated in malignancy. In turn, miRNAs themselves are targets of E2F family proteins establishing negative feedback loops. Since individual miRNAs may regulate hundreds of genes, these findings add a new challenging layer of complexity to the E2F network that possibly helps to make cell fate decisions. This review outlines our current understanding of the checks and balances of E2Fs and microRNAs in the context of a seemingly paradoxical role in cancer control. PMID- 20581446 TI - The Hippo in the room: a new look at a key pathway in cell growth and transformation. AB - During development and in cancer, tissue and cell growth control requires coordinated regulation of cell proliferation and apoptosis. The tumor suppressive Hippo pathway plays a key role in size regulation and cell-contact inhibition. During the past decade, this pathway has been delineated in Drosophila and now is starting to be better understood in mammals, where an increasing level of complexity and cell context specificity is becoming evident. As we discuss, dys regulation of this pathway at any step can lead to uncontrolled growth and tumor formation. Indeed, a majority of the pathway components have been implicated in human cancers. PMID- 20581445 TI - Identification and characterization of a novel agonistic anti-DR4 human monoclonal antibody. AB - The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been established as promising targets for cancer treatment. Therapeutics targeting TRAIL and its receptors are not only effective in killing many types of tumors, but they also synergize with traditional therapies and show efficacy against tumors that are otherwise resistant to conventional treatments. We describe here the identification and characterization of two human monoclonal antibodies, m921 and m922, that are specific for human DR4. Both antibodies competed with TRAIL for binding to DR4, but only m921 recognized cell surface-associated DR4 and inhibited the growth of ST486 cells. This antibody may have potential for further development as a candidate therapeutic and research tool. PMID- 20581447 TI - RIP-in CD95-induced cell death: The control of alternative death receptors pathways by cIAPs. PMID- 20581448 TI - SON is a spliceosome-associated factor required for mitotic progression. AB - The eukaryotic RNA splicing machinery is dedicated to the daunting task of excising intronic sequences on the many nascent RNA transcripts in a cell, and in doing so facilitates proper translation of its transcriptome. Notably, emerging evidence suggests that RNA splicing may also play direct roles in maintaining genome stability. Here we report the identification of the RNA/DNA-binding protein SON as a component of spliceosome that plays pleiotropic roles during mitotic progression. We found that SON is essential for cell proliferation, and that its inactivation triggers a MAD2-dependent mitotic delay. Moreover, SON deficiency is accompanied by defective chromosome congression, compromised chromosome segregation and cytokinesis, which in turn contributes to cellular aneuploidy and cell death. In summary, our study uncovers a specific link between SON and mitosis, and highlights the potential of RNA processing as additional regulatory mechanisms that govern cell proliferation and division. PMID- 20581449 TI - Centrosomal Chk2 in DNA damage responses and cell cycle progression. AB - Two major control systems regulate early stages of mitosis: activation of Cdk1 and anaphase control through assembly and disassembly of the mitotic spindle. In parallel to cell cycle progression, centrosomal duplication is regulated through proteins including Nek2. Recent studies suggest that centrosome-localized Chk1 forestalls premature activation of centrosomal Cdc25b and Cdk1 for mitotic entry, whereas Chk2 binds centrosomes and arrests mitosis only after activation by ATM and ATR in response to DNA damage. Here, we show that Chk2 centrosomal binding does not require DNA damage, but varies according to cell cycle progression. These and other data suggest a model in which binding of Chk2 to the centrosome at multiple cell cycle junctures controls co-localization of Chk2 with other cell cycle and centrosomal regulators. PMID- 20581450 TI - Leveraging combinatorial chemotherapy to improve outcomes in patients with pancreatic cancer. PMID- 20581451 TI - Dissection of mitotic functions of the yeast cyclin Clb2. AB - Progression through mitosis requires the activity of cyclin-dependent kinases (CDKs) associated with regulatory cyclin subunits. In the yeast Saccharomyces cerevisiae, Clb2 has the most important role among the four mitotic cyclins, Clb1 4, manifested by data showing that simultaneous deletion of the CLB1, CLB3 and CLB4 genes has only minor effects on mitosis. Thus, Clb2 alone is sufficient for all essential CDK functions in mitosis, such as the assembly of bipolar spindles and spindle elongation. Here, we show that a modification of Clb2, by the C terminal addition of a Myc12 epitope, causes the loss of one specific mitotic function of Clb2. Strains carrying CLB2-MYC12 are nonviable in the absence of the CLB3 and CLB4 genes, because the modified Clb2 version fails to promote assembly of the mitotic spindle. In contrast, Clb2-Myc12 has no apparent defects in late mitotic functions and, furthermore, induces the switch from polarized to isotropic growth with similar efficiency as the endogenous Clb2. Thus, the presence of the Myc12 epitope selectively inactivates Clb2's capacity to promote spindle formation. Clb2-Myc12 represents therefore the first version of Clb2 impaired in one specific mitotic function. We conclude that the major mitotic functions of this cyclin can be unequivocally dissected. PMID- 20581452 TI - Polycomb complexes - Genes make sense of host defense. PMID- 20581453 TI - Mitotic DNA damage response: Polo-like kinase-1 is dephosphorylated through ATM Chk1 pathway. AB - DNA damage during the cell division cycle can activate ATM/ATR and their downstream kinases that are involved in the checkpoint pathway, and cell growth is halted until damage is repaired. As a result of DNA damage induced in mitotic cells by doxorubicin treatment, cells accumulate in a G2-like phase, not in mitosis. Under these conditions, two mitosis-specific kinases, Cdk1 and Plk1, are inhibited by inhibitory phosphorylation and dephosphorylation, respectively. G2 specific phosphorylation of Cdc25 was increased during incubation after mitotic DNA damage. Inhibition of Plk1 through dephosphorylation was dependent on ATM/Chk1 activity. Depleted expression of ATM and Chk1 was achieved using small hairpin RNA (shRNA) plasmid constructs. In this condition, damaged mitotic cells did not accumulated in a G2-like stage, and entered into G1 phase without delay. Protein phosphatase 2A was responsible for dephosphorylation of mitotic Plk1 in response to DNA damage. In knockdown of PP2A catalytic subunits, Plk1 was not dephosphorylated, but rather degraded in response to DNA damage, and cells did not accumulate in G2-like phase. The effect of ATM/Chk1 inhibition was counteracted by overexpression of PP2A, indicated that PP2A may function as a downstream target of ATM/Chk1 at a mitotic DNA damage checkpoint, or may have a dominant effect on ATM/Chk1 function at this checkpoint. Finally, we have shown that negative regulation of Plk1 by dephosphorylation is important to cell accumulation in G2-like phase at the mitotic DNA damage checkpoint, and that this ATM/Chk1/PP2A pathway independent on p53 is a novel mechanism of cellular response to mitotic DNA damage. PMID- 20581455 TI - Disruption of calvarial ossification in E2f4 mutant embryos correlates with increased proliferation and progenitor cell populations. AB - The E2F family of transcription factors, in association with pocket protein family members, are important for regulating genes required for cellular proliferation. The most abundant E2F, E2F4, is implicated in maintaining the G(0)/G(1) cell cycle state via transcriptional repression of genes that encode proteins required for S-phase progression. Here, we investigate E2F4's role in bone development using E2f4 germline mutant mice. We find that mutation of E2f4 impairs the formation of several bones that arise through intramembranous or endochondral ossification. The most severe defect occurred in the calvarial bones of the skull where we observed a striking delay in their ossification. In vivo and in vitro analyses established that E2F4 loss did not block the intrinsic differentiation potential of calvarial osteoblast progenitors. However, our data showed that E2f4 mutation elevated proliferation in the developing calvaria in vivo and it increased the endogenous pool of undifferentiated progenitor cells. These data suggest that E2F4 plays an important role in enabling osteoblast progenitors to exit the cell cycle and subsequently differentiate thereby contributing to the commitment of these cells to the bone lineage. PMID- 20581456 TI - Interdependent regulation of p53 and miR-34a in chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) has an incidence 4/1,00,000 people in the western world and is one of the first cancers reported to be associated with deregulated miRNA expression. microRNAs are small non coding RNAs that are important regulators of protein expression through binding to their untranslated 3'-UTR region. The miR-34 family was demonstrated to be induced by the tumor suppressor p53 and to elicit p53-like responses like senescence, cell cycle arrest and apoptosis depending on the cell type. We have shown in a recent paper that miR-34a is severely increased in the TCL1-mouse model of CLL. This finding was reflected in human CLL. Moreover, it is demonstrated that its expression is dependent on the presence of the SNP309 in the intronic promoter of the MDM2 gene. In addition, low miR-34a expression was associated with shorter time to treatment (log-rank p = 0.003) in CLL. When reintroduced into CLL cells, miR-34a was able to induce apoptosis. Interestingly, this was dependent on an intact p53 pathway. Here, we present data showing that knockdown of p53 in HCT-116 cells severely reduces miR-34a induced apoptosis. In conclusion, miR-34a is proposed as a marker for the activity of the p53 pathway in CLL. PMID- 20581454 TI - Impact of the hypoxic tumor microenvironment on the regulation of cancer stem cell characteristics. AB - Solid tumors often contain regions with insufficient oxygen delivery, a condition called hypoxia. Tumor hypoxia is an independent prognostic factor significantly correlated with advanced stages of malignancy, increased resistance to conventional therapy, and reduced disease-free survival. Hypoxic tumor cells exhibit poorly differentiated phenotypes resembling stem or progenitor cells. Studies have shown that hypoxia can inhibit tumor cell differentiation and promote maintenance of cancer stem cells. In addition, hypoxia also blocks the differentiation of mesenchymal stem/progenitor cells, a potential source of tumor associated stromal cells. Therefore, hypoxia may play a critical role during the evolution of the tumor stromal microenvironment and formation of the putative cancer stem cell niches. Conceptually, hypoxia may help create a microenvironment enriched both in poorly differentiated tumor cells and in undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This review will discuss the hypoxia-regulated stem cell pathways and their roles in the maintenance of cancer stem cell functions. PMID- 20581457 TI - Long antisense non-coding RNAs and their role in transcription and oncogenesis. AB - Long non-coding RNAs are estimated to qualitatively represent ~98% of expressed transcripts in human cells, a large proportion of which is antisense to protein coding and non-coding transcripts. Here we review evidence from several experimental systems that suggests long antisense non-coding RNAs are involved in the transcriptional regulation of gene expression by altering epigenetic states at both adjacent and distal loci. We also review the initial evidence for a role of endogenous long antisense non-coding RNAs in oncogenic cellular transformation. PMID- 20581458 TI - Oncogenic c-kit transcript is a target for binase. AB - Mutational activation of c-Kit receptor tyrosine kinase is common in acute myelogenous leukemia (AML). One such activating point mutation is the N822K replacement in the c-Kit protein. Here we investigate the selective cytotoxic effect of binase--RNase from Bacillus intermedius--on FDC-P1-N822K cells. These cells were derived from myeloid progenitor FDC-P1 cells, in which ectopic expression of N822K c-kit gene induces interleukin-3 independent growth. In order to determine whether the sensitivity of these cells to binase is caused by the expression of c-kit oncogene, the cytotoxicity of the RNase was studied in the presence of selective inhibitor of mutated c-Kit imatinib (Gleevec). Inhibition of mutated c-Kit protein leads to the loss of cell sensitivity to the apoptotic effect of binase, while the latter still decreases the amount of cellular RNA. Using green fluorescent protein as an expression marker for the c-Kit oncoprotein, we demonstrate that the elimination of c-Kit is the key factor in selective cytotoxicity of binase. Quantitative RT-PCR with RNA samples isolated from the binase-treated FDC-P1-N822K cells shows that binase treatment results in 41% reduction in the amount of s-kit mRNA. This indicates that the transcript of the activated mutant c-kit is the target for toxic action of binase. Thus, the combination of inhibition of oncogenic protein with the destruction of its mRNA is a promising approach to eliminating malignant cells. PMID- 20581459 TI - Exposure to acute hypoxia induces a transient DNA damage response which includes Chk1 and TLK1. AB - Severe hypoxia has been demonstrated to induce a replication arrest which is associated with decreased levels of nucleotides. Chk1 is rapidly phosphorylated in response to severe hypoxia and in turn deactivates TLK1 through phosphorylation. Loss of Chk1 has been shown to sensitize cells to hypoxia/reoxygenation. After short (acute) exposure to hypoxia this is due to an increased rate of reoxygenation-induced replication restart and subsequent p53 dependent apoptosis. After longer (chronic) exposure to hypoxia S phase cells do not undergo reoxygenation-induced replication restart. Cells exposed to these levels of hypoxia however are sensitive to loss of Chk1. This suggests a new role for Chk1 in the cell cycle response to reoxygenation. PMID- 20581460 TI - What happens when replication and transcription complexes collide? AB - The arrest of replication forks due to collisions with transcription complexes leads to genomic instability and cell death. Mechanisms that promote the progression of replication forks past transcription complexes are therefore essential for propagation and preservation of the genome. Recent studies of E. coli directly investigate the consequences of collisions of the replisome with RNAP polymerase (RNAP) in vitro and provide novel mechanisms by which these encounters may be resolved. Additionally, recent in vivo and in vitro studies support the longstanding hypothesis that auxiliary DNA helicases promote replication through roadblocks such as transcription complexes. Here we review past and recent advances that formulate our current understanding of how the bacterial replisome deals with transcription complexes along the path of chromosome duplication. PMID- 20581461 TI - BAR domain competition during directional cellular migration. AB - While directed cellular migration facilitates the coordinated movement of cells during development and tissue repair, the precise mechanisms regulating the interplay between the extracellular environment, the actin cytoskeleton, and the overlying plasma membrane remain inadequately understood. The BAR domain family of lipid binding, actin cytoskeletal regulators are gaining greater appreciation for their role in these critical processes. BAR domain proteins are involved as both positive and negative regulators of endocytosis, membrane plasticity, and directional cell migration. This review focuses on the functional relationship between different classes of BAR domain proteins and their role in guiding cell migration through regulation of the endocytic machinery. Competition for key signaling substrates by positive and negative BAR domain endocytic regulators appears to mediate control of directional cell migration, and may have wider applicability to other trafficking functions associated with development and carcinogenesis. PMID- 20581462 TI - Recombinant antibodies specific for the Plasmodium falciparum histidine-rich protein 2. AB - Early diagnosis and appropriate treatment are key elements of malaria control programs in endemic areas. A major step forward in recent years has been the production and use of rapid diagnostic tests (RDTs) in settings where microscopy is impracticable. Many current RDTs target the Plasmodium falciparum histidine rich protein 2 (PfHRP2) released in the plasma of infected individuals. These RDTs have had an indisputably positive effect on malaria management, but still present several limitations, including the poor characterization of the commercial monoclonal antibodies (mAbs) used for PfHRP2 detection, variable sensitivity and specificity, and high costs. RDT use is further limited by impaired stability caused by temperature fluctuations during transport and uncontrolled storage in field-based facilities. To circumvent such drawbacks, an alternative could be the development of well-characterized, stabilized recombinant antibodies, with high binding affinity and specificity. Here, we report the characterization of the cDNA sequences encoding the Fab fragment of F1110 and F1546, two novels anti-PfHRP2 mAbs. FabF1546 was produced in the Escherichia coli periplasm. Its properties of binding to the parasite and to a recombinant PfHRP-2 antigen were similar to those of the parental mAb. As the affinity and stability of recombinant antibodies can be improved by protein engineering, our results open a novel approach for the development of an improved RDT for malaria diagnosis. PMID- 20581463 TI - Casein kinase 1 is required for efficient removal of Rec8 during meiosis I. AB - Segregation of chromosomes during meiosis depends on separase cleavage of Rec8, the meiosis-specific alpha-kleisin subunit of cohesin. We mapped Rec8 phosphorylation sites by mass spectrometry and show that Rec8 phosphorylation is required for proper chromosome disjunction during meiosis. We further show that the fission yeast casein kinase 1 (CK1) delta/epsilon isoforms Hhp1 and Hhp2 are required for full levels of Rec8 phosphorylation and for efficient removal of Rec8 at the onset of anaphase I. Our data are consistent with the model that Hhp1/Hhp2-dependent phosphorylation of Rec8 is required for separase-mediated cleavage of Rec8 during meiosis I. PMID- 20581464 TI - The effect of ATM knockdown on ionizing radiation-induced neuronal cell cycle reentry in Drosophila. PMID- 20581466 TI - mTORC1 signaling in Parkinson's disease and L-DOPA-induced dyskinesia: A sensitized matter. AB - Parkinson disease is caused by the progressive loss of dopamine innervation to the basal ganglia and is commonly treated with the dopamine precursor, L-DOPA. Prolonged administration of L-DOPA results in the development of severe motor complications or dyskinesia, which seriously hamper its clinical use. Recent evidence indicates that L-DOPA-induced dyskinesia (LID) is associated with persistent activation of the mammalian target of rapamycin complex 1 (mTORC1) in the medium spiny neurons (MSNs) of the striatum, the main component of the basal ganglia. This phenomenon is secondary to the development of a strong sensitization at the level of dopamine D1 receptors, which are abundantly expressed in a subset of MSNs. Such sensitization confers to dopaminergic drugs (including L-DOPA) the ability to activate the extracellular signal-regulated protein kinases 1/2, which, in turn promote mTORC1 signaling. Using a mouse model of LID, we recently showed that administration of the allosteric mTORC1 inhibitor, rapamycin, reduces dyskinesia. This finding is discussed with respect to underlying mechanisms and potential significance for the development of future therapeutic interventions. PMID- 20581465 TI - BRCA1 regulation of base excision repair pathway. PMID- 20581469 TI - Genetic variant associated with aggressive not indolent prostate cancer. PMID- 20581468 TI - Dendritic cells-mediated CTLs targeting hepatocellular carcinoma stem cells. AB - Immunotherapy, especially using dendritic cells (DCs)-based vaccine, appears promising in the treatment of hepatocellular carcinoma (HCC) following surgery. However, the therapeutic efficacy of current DC vaccines loaded with HCC antigen is limited in clinical practice. One important reason might be that the DC vaccines for the treatment of HCC were not aimed at targeting the hepatocellular carcinoma cancer stem cells (HCCCSCs). Therefore, establishing an immunotherapy to kill HCC stem cells could be a novel therapeutic strategy. In this study, we have developed an immunotherapy to target CD133(+) HCC cells in the treatment of HCC. This study had three main findings; (1) CD133(+)HCC cells RNA loaded DCs could induce special CD8(+) cytotoxic T lymphocytes (CD133(+)Huh7-CTLs) response against CD133(+) Huh7 cells in vitro. (2) Huh7 cells-induced tumor growth in vivo was effectively inhibited by CD133(+)Huh7-CTLs. (3) the great inhibition potential of CD133(+)Huh7-CTLs to Huh7-induced tumor growth might not be only associated with anti-tumor cytokines such as IFNgamma, but also to CD133(+)Huh7 DCs induced specific CTLs. This study shows an experimental proof that CD133(+)HCC cells RNA loaded DC vaccine has potential in treating HCC and may provide a new therapy for clinical post operative adjuvant therapy in future. PMID- 20581467 TI - DeltaNp73beta is oncogenic in hepatocellular carcinoma by blocking apoptosis signaling via death receptors and mitochondria. AB - BACKGROUND & AIMS: p73 belongs to the p53 family of transcription factors known to regulate cell cycle and apoptosis. The Trp73 gene has two promoters that drive the expression of two major p73 isoform subfamilies: TA and DeltaN. In general, TAp73 isoforms show proapoptotic activities, whereas members of the N-terminally truncated (DeltaN) p73 subfamily that lack the transactivation domain show antiapoptotic functions. We found that upregulation of DeltaNp73 in hepatocellular carcinoma (HCC) correlated with reduced survival. Here, we investigated the molecular mechanisms accounting for the oncogenic role of DeltaNp73 in HCC. RESULTS: DeltaNp73beta can directly interfere with the transcriptional activation function of the TA (containing the transactivation domain) isoforms of the p53 family and consequently inhibit transactivation of proapoptotic target genes. Interference of DeltaNp73beta with apoptosis /chemosensitivity takes place at several levels of apoptosis signaling. DeltaNp73beta negatively regulates the genes encoding for the death receptors CD95, TNF-R1, TRAIL-R2 and TNFRSF18. Furthermore, DeltaNp73beta represses the genes encoding caspase-2, -3, -6, -8 and -9. Concomitantly, DeltaNp73beta inhibits apoptosis emanating from mitochondria. CONCLUSIONS: Thus, DeltaNp73 expression in HCC selects against both the death receptor and the mitochondrial apoptosis activity of the TA isoforms. Our data suggest that DeltaNp73 isoforms repress apoptosis-related genes of the extrinsic and intrinsic apoptosis signaling pathways thereby contributing to chemoresistance. The clinical importance of these data is evidenced by our finding that the DeltaNp73beta target gene signature can predict the prognosis of patients suffering from HCC. PMID- 20581471 TI - Close encounters of a novel kind: a multi-targeted cancer drug meets a metabolic sensor. PMID- 20581470 TI - Cross-linking of DeltaF508-CFTR promotes its trafficking to the plasma membrane. AB - CFTR is a cAMP-activated chloride channel responsible for agonist stimulated chloride and fluid transport across epithelial surfaces.(1) Mutations in the CFTR gene lead to cystic fibrosis (CF) which affects the function of secretory organs like the intestine, the pancreas, the airways and the sweat glands. Most of the morbidity and mortality in CF has been linked to a decrease in airway function.(2) The DeltaF508 mutation is the most common CF-related mutation in the Caucasian population and represents 90% of CF alleles. Homozygote carriers of this mutation present with a severe CF phenotype.(3) The DeltaF508 mutation causes misfolding of the nascent CFTR polypeptide, which leads to inefficient export from the endoplasmic reticulum (ER) and rapid degradation by the proteasome. PMID- 20581472 TI - Mammalian Atg8s: one is simply not enough. PMID- 20581473 TI - Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM). AB - Over 20,000 genes were recently sequenced in a series of 24 pancreatic cancers. We applied CHASM (Cancer-specific High-throughput Annotation of Somatic Mutations) to 963 of the missense somatic missense mutations discovered in these 24 cancers. CHASM identified putative driver mutations (false discovery rate <=0.3) in three known pancreatic cancer driver genes (P53, SMAD4, CDKN2A). An additional 15 genes with putative driver mutations include genes coding for kinases (PIK3CG, DGKA, STK33, TTK and PRKCG), for cell cycle related proteins (NEK8), and for proteins involved in cell adhesion (CMAS, PCDHB2). These and other mutations identified by CHASM point to potential "driver genes" in pancreatic cancer that should be prioritized for additional follow-up. PMID- 20581474 TI - Unique gating properties of C. elegans ClC anion channel splice variants are determined by altered CBS domain conformation and the R-helix linker. AB - All eukaryotic and some prokaryotic ClC anion transport proteins have extensive cytoplasmic C-termini containing two cystathionine-beta-synthase (CBS) domains. CBS domain secondary structure is highly conserved and consists of two alpha helices and three beta-strands arranged as beta1-alpha1-beta2-beta3-alpha2. ClC CBS domain mutations cause muscle and bone disease and alter ClC gating. However, the precise functional roles of CBS domains and the structural bases by which they regulate ClC function are poorly understood. CLH-3a and CLH-3b are C. elegans ClC anion channel splice variants with strikingly different biophysical properties. Splice variation occurs at cytoplasmic N- and C-termini and includes several amino acids that form alpha2 of the second CBS domain (CBS2). We demonstrate that interchanging alpha2 between CLH-3a and CLH-3b interchanges their gating properties. The "R-helix" of ClC proteins forms part of the ion conducting pore and selectivity filter and is connected to the cytoplasmic C terminus via a short stretch of cytoplasmic amino acids termed the "R-helix linker". C-terminus conformation changes could cause R-helix structural rearrangements via this linker. X-ray structures of three ClC protein cytoplasmic C-termini suggest that alpha2 of CBS2 and the R-helix linker could be closely apposed and may therefore interact. We found that mutating apposing amino acids in alpha2 and the R-helix linker of CLH-3b was sufficient to give rise to CLH-3a like gating. We postulate that the R-helix linker interacts with CBS2 alpha2, and that this putative interaction provides a pathway by which cytoplasmic C-terminus conformational changes induce conformational changes in membrane domains that in turn modulate ClC function. PMID- 20581475 TI - Voltage dependent anion channel-1 (VDAC-1) as an anti-cancer target. PMID- 20581476 TI - A novel Gfer-Drp1 link in preserving mitochondrial dynamics and function in pluripotent stem cells. AB - Mitochondria, the dynamic energy powerhouses of the cell, have vital roles in a multitude of cellular processes including differentiation and cell survival. Tight regulation of mitochondrial dynamics, integrity and function is indispensible for preservation of homeostasis in all cells, including pluripotent stem cells. The ability to proliferate and self-renew indefinitely bestows the pluripotent embryonic stem cells (ESCs) with immense curative potential. Mechanisms that preserve mitochondrial well-being, and therefore maintain "stemness," are vital in realizing the full potential of ESCs in therapeutic regenerative medicine. However, virtually nothing is known regarding the regulation of mitochondrial dynamics and function and the relationship thereof to overall cell fate and function in pluripotent ESCs or other somatic stem cells. Using loss- and gain-of-function approaches, we show that growth factor erv1-like (Gfer) plays an essential pro-survival role in the maintenance of murine ESC pluripotency by preserving the structural and functional integrity of their mitochondria, through modulation of the key mitochondrial fission factor Drp1. PMID- 20581573 TI - Stereotactic body radiation therapy for early-stage lung cancer: are we "all in". PMID- 20581574 TI - Multiple primary cancers or multiple metastases, that is the question. PMID- 20581576 TI - Annual review of advances in lung cancer clinical research: a report for the year 2009. AB - The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms. PMID- 20581575 TI - Randomized phase II trials: time for a new era in clinical trial design. AB - The classic single-arm oncology phase II trial designs for evaluating an experimental regimen/agent are limited by multiple sources of bias arising from the inability to separate trial effects (such as patient selection, trial eligibility, imaging techniques and assessment schedule, and treatment locations) from treatment effect on clinical outcomes. Changes in patient population based on biologic subsetting, newer imaging technologies, the use of alternative end points, constrained resources, and the multitude of promising therapies for a given disease make randomized phase II designs, with a concurrent control arm where necessary, attractive. In this brief report, we discuss the salient features of the randomized designs for phase II trials, which when properly applied under the constraints of their underlying inference framework can assure optimal use of limited phase III financial and patient resources. PMID- 20581577 TI - Giant alveolar adenoma causing severe dyspnoea. PMID- 20581578 TI - Tumor necrosis and cavitation after stereotactic body radiation therapy. PMID- 20581579 TI - Successful treatment with erlotinib after gefitinib-induced severe interstitial lung disease. PMID- 20581580 TI - Successful erlotinib rechallenge after gefitinib-induced acute interstitial pneumonia. PMID- 20581581 TI - Treatment of pulmonary epithelioid hemangioendothelioma with bevacizumab. PMID- 20581582 TI - Erlotinib and gastrointestinal ulcer. PMID- 20581584 TI - The role of surgery in the management of primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma. PMID- 20581591 TI - Stand tall against shortcomings. PMID- 20581594 TI - Transitions into nursing: the new graduate nurse experience. PMID- 20581595 TI - Using incident reports as a teaching tool. PMID- 20581596 TI - Sharing data to ensure continuity of care. PMID- 20581597 TI - Transfusion confusion. PMID- 20581599 TI - Shared governance: 10 years later. PMID- 20581600 TI - Is failure to rescue really failure to communicate? Champion the move from reactive process to proactive model. PMID- 20581601 TI - The Magnetic pull. PMID- 20581602 TI - Treating obstructive sleep apnea with CPAP. PMID- 20581603 TI - Close the door on crisis management. PMID- 20581615 TI - Benefit and quality of life in older bone-anchored hearing aid users. AB - OBJECTIVE: Benefit and quality-of-life analysis in the older adult bone-anchored hearing aid (BAHA) users. STUDY DESIGN: Retrospective evaluation. METHODS: Four questionnaires (Glasgow Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit [APHAB], Nijmegen Cochlear Implant Questionnaire [NCIQ], and the Hearing Handicap Inventory for the Elderly screening version [HHIE-S]) were used. RESULTS: The response rate was 80%, mean age was 75 years (range, 62-93 yr), and mean pure-tone average at frequencies of 500, 1,000, 2,000, and 4,000 Hz for bone conduction was 42 +/- 13 dBHL. More than 80% of the patients were using their BAHA for more than 8 hours a day. To obtain a "snapshot" of current BAHA use, the NCIQ, HHIE-S, and the APHAB were used. The NCIQ showed good disability and handicap results (score range, 49-64). The HHIE-S showed that 60% of the patients had a mild to moderate handicap. The APHAB aided scores ranged from 39 to 58%. Mean benefit scores of the Glasgow Benefit Inventory were positive in 112 of the 134 patients (84%). The APHAB showed clinically significantly more benefit with the BAHA than with the previous aided or unaided situation. A trend could be seen the higher the pure-tone average at frequencies of 500, 1,000, 2,000, and 4,000 Hz for bone conduction, the smaller the mean benefit scores on the questionnaires. CONCLUSION: Bone-anchored hearing aid users aged 60 years or older were able to place and handle the device very adequately and clean the skin around the implant. Most patients reported comparable or increased general benefit and good quality of life with the BAHA. PMID- 20581646 TI - Neuromuscular junction disease or neuropathic disorder? PMID- 20581647 TI - Optimization and reliability of a deep water running test in healthy adults older than 45 years. AB - OBJECTIVE: The aim of this study was to (1) compare the peak oxygen uptake across three protocols of different duration during an incremental deep water running test to exhaustion; (2) study the reproducibility of peak Vo2 during two repeated incremental deep water running tests; (3) compare peak deep water running test and treadmill cardiopulmonary responses in adults older than 45 yrs. DESIGN: First, 24 healthy subjects older than 45 yrs (60 yrs [6 yrs], body mass index: 28 kg/m [6 kg/m], 11 men/13 women) performed three incremental deep water running tests (< or =8 mins, 8-12 mins, and > or =12 mins) with measurement of peak Vo2 (optimization group). Nineteen subjects of the 24 original subjects (reproducibility group) then performed two repeated maximal deep water running tests. Finally, 21 of the 24 original subjects also performed an additional maximal treadmill test (comparison group). Peak Vo2 was compared with analyses of variance for repeated measurements for the optimization, reproducibility, and comparison groups. RESULTS: Peak Vo2 (ml/min) did not differ according to protocol duration (short: 1529 [674]; intermediate, 1456 [594]; and long, 1465 [674] ml/min, P = 0.53), was reproducible with an intraclass correlation coefficient of 0.90 (P < 0.0001), and was lower compared with treadmill (deep water running test: 1615 [586] vs. T: 2545 [511] ml/min, P < 0.0001). CONCLUSIONS: A 6- to 12-min protocol duration can be used to assess deep water running test peak Vo2, which is reproducible and lower compared with that obtained on the treadmill in healthy subjects older than 45 yrs. PMID- 20581648 TI - The effect of back school integrated with core strengthening in patients with chronic low-back pain. AB - OBJECTIVE: To assess the effect of back school integrated with core-strengthening exercises on back-specific disability and pain-coping strategies and to examine how reactions to pain affect the outcomes of back school in patients with chronic low back pain. DESIGN: A single-center prospective trial was conducted with 142 participants with chronic low-back pain (38 men and 104 women) who completed a back school program at the spine center of a university hospital. The subjects participated in a 4-wk program integrated with core-strengthening exercises. Back specific disabilities were measured as a primary outcome before and after the program. Secondary outcomes were pain, Chronic Pain Coping Inventory, general health status assessed by the SF-36, and quantitative functional evaluations of factors, such as trunk muscle strength, endurance, and the back performance scale. A subgroup of 28 subjects (12 men and 16 women) of the total sample of 142 subjects was used to analyze the longitudinal association between coping strategies and the primary outcome in a long-term follow-up study. These participants were divided into three groups (much improved, slightly improved, and unimproved) based on changes in back-specific disability scores. RESULTS: Participants improved significantly in terms of back-specific disability, pain, general health, and quantitative functional tests according to the short-term evaluation. They used more relaxation and exercise/stretching techniques as coping strategies. Of the groups participating in the longer-term follow-up (T3), the much-improved group showed significant improvement between T1 (before back school) and T2 (after back school) in scores for relaxation (1.6 +/- 1.0 vs. 2.6 +/- 1.1), task persistence (2.9 +/- 1.2 vs. 3.7 +/- 1.2), and exercise (3.3 +/- 1.1 vs. 5.2 +/- 1.9), but the coping strategies of those in the slightly improved and unimproved groups did not change significantly at T2. CONCLUSIONS: Our back school program may help patients with chronic low back pain reduce back-specific disability and pain and develop wellness-focused coping strategies such as exercise and stretching. PMID- 20581649 TI - Carpal lock and the volar-supporting orthosis in mild and moderate carpal tunnel syndrome. AB - OBJECTIVE: The carpal lock, which is a hand/wrist orthosis that supports the dorsal aspect of the hand, was used in patients with mild-moderate carpal tunnel syndrome, and its clinical and electrophysiological effectiveness was compared with that of a volar-supporting orthosis. DESIGN: Nerve conduction study and clinical evaluation of 24 patients (41 hands) with mild or moderate carpal tunnel syndrome were performed before and 3 mos after the use of the carpal lock or the volar-supporting orthosis. RESULTS: Significant improvement was observed in electrophysiological parameters and clinical outcomes after use of both orthoses. There was no statistically significant difference between the two groups. Patients in the carpal lock group used the orthosis 89.6% of the prescribed time, whereas those in the volar-supporting orthosis group used the orthosis 79.2% of the prescribed time (P < 0.05). CONCLUSIONS: The carpal lock may be used as an alternative to the volar-supporting orthosis. PMID- 20581650 TI - Downhill walking training in individuals with Parkinson's disease: a randomized controlled trial. AB - OBJECTIVE: The purpose of this study was to examine the effects of downhill walking training on gait and thoracic kyphosis in patients with Parkinson's disease. DESIGN: Thirty-three patients with Parkinson's disease were randomized into an experimental group (n = 16) or a control group (n = 17). Subjects in the experimental group underwent 4-wks of downhill walking training, whereas subjects in the control group received conventional therapy for 4 wks. Gait parameters, thoracic kyphosis, and muscle strength of knee were measured at pretraining, posttraining, and at 1-mo follow-up. RESULTS: There were significant interaction effects between group and time of evaluation on gait parameters and thoracic kyphotic curve. There was also a significant group effect for muscle strength of knee extensors. CONCLUSIONS: Our results suggest that downhill walking training is beneficial for improving gait performance in patients with Parkinson's disease and may contribute to maintenance of thoracic posture in these subjects. PMID- 20581651 TI - Segmental zoster paresis of the left upper limb in a pediatric patient. AB - Segmental zoster paresis of the left upper limb in a pediatric patient.Segmental zoster paresis is a rare complication of herpes zoster characterized by focal, asymmetrical motor weakness in the myotome that corresponds to the dermatome of the rash. Segmental zoster paresis typically develops within 2-3 wks of cutaneous zoster and predominantly affects the middle-aged and elderly populations. Motor complications rarely develop in children and young adults, but when they do develop, involvement is usually confined to cranial and truncal muscles, with sparing of the limb musculature. A 10-yr-old boy with Fanconi's anemia developed left upper limb weakness because of involvement of C5 motor roots as a complication of herpes zoster. Recognizing motor zoster as a cause of acute motor weakness in a pediatric patient is important in avoiding unnecessary interventions and optimizing treatment. PMID- 20581652 TI - Accuracy of the glenohumeral injection using the superior approach: a cadaveric study of injection accuracy. AB - OBJECTIVE: The glenohumeral joint can be accessed by anterior, posterior, or superior approach. Blind shoulder injections using anterior or posterior approach have been often inaccurate and infiltrated untargeted structures. The aim of this study was to investigate the success rate of injections in the glenohumeral joint using the superior approach. DESIGN: Nineteen shoulders from 12 adult cadavers were anatomically dissected after a dye injection had been performed, with cadavers in the supine position. A clinician rated injection confidence scores. The dissectors rated injection accuracy scores and investigated untargeted structures penetrated. RESULTS: The clinician's confidence scores were the highest in 18 of 19 shoulders. Superior glenohumeral injections were successful in 18 of 19 (94.7%) shoulders; however, in 3 of these 18 shoulders, the long heads of biceps tendons were penetrated. CONCLUSIONS: The glenohumeral joint injection using the superior approach is accurate and clinically useful, but caution for the likelihood of penetrating the long head of biceps tendon should be considered. PMID- 20581653 TI - Life-threatening asymptomatic incidentaloma: a case report of idiopathic CD4 lymphocytopenia and opportunistic infections. AB - Incidental lung nodules can be due to a variety of etiologies. Management is guided by the most likely or urgent pathology, which is frequently malignancy in an elderly smoker. We present the case of a 62-year-old, long-time smoker, with an incidental lung nodule. Pursuit of the underlying etiology revealed disseminated cryptococcal and Mycobacterium avium intracellulare infections, which are most often seen in patients with advanced human immunodeficiency virus acquired immunodeficiency syndrome or other immunocompromise. This patient was ultimately determined to have idiopathic CD4 lymphocytopenia, a rare and poorly understood acquired immunodeficiency syndrome. Furthermore, Cryptococcus neoformans is well known to cause asymptomatic meningitis in immunocompetent individuals but is very rarely asymptomatic in the immunosuppressed, as was the case with this patient. PMID- 20581654 TI - Lower urinary tract involvement in patients with newly diagnosed autoimmune bullous dermatoses: an urethrocystoscopic study. AB - INTRODUCTION: To date, there are no published data assessing lower urinary tract involvement in patients with autoimmune bullous dermatoses (ABD). METHODS: Fourteen of 30 consecutive patients diagnosed with ABD between October 2007 and December 2008 consented to undergo a diagnostic video-recorded urethrocystoscopy: 9 patients (7 women and 2 men) with pemphigus vulgaris, 4 patients (2 women and 2 men) with bullous pemphigoid and 1 female patient with mucous membrane pemphigoid. RESULTS: None of the 14 patients complained of lower urinary tract symptoms. Urethrocystoscopy disclosed characteristic lower urinary tract lesions in almost every patient with ABD (13 of 14 patients; 93%). Two, partly overlapped, pathologic patterns prevailed: (a) nonkeratinizing squamous metaplasia (SM) found in 64% of the patients, including 2 of 4 men; (b) mucosal inflammation of the bladder base/trigone that extended-especially among male patients-to the proximal urethra (64% of the patients). SM prevailed among patients with pemphigus vulgaris, inflammatory lesions among patients with bullous pemphigoid (P = 0.003) and involvement of proximal urethra among male patients (P = 0.004), irrespective of the particular ABD diagnosis. CONCLUSIONS: The authors present, to the best of their knowledge, for the first time in the literature, urethrocystoscopic evidence that inflammatory urothelial lesions of the bladder and proximal urethra confounded with nonkeratinizing SM of the trigone are an almost invariable finding in patients with ABD. Studies focusing on the elucidation of the pathomechanism of bladder lesions in these patients may contribute to the better understanding of both the pathophysiology of the bullous skin diseases and the pathobiology of the bladder urothelium. PMID- 20581655 TI - The interaction of ACP1, ADA1, diabetes and gender in coronary artery disease. AB - INTRODUCTION: Previous separate studies have shown associations of coronary artery disease (CAD) with acid phosphatase locus 1 (ACP1) and adenosine deaminase locus 1 (ADA1) genetic polymorphisms. Because it is known that the 2 systems interact and have important immunologic and metabolic functions, these 2 genes were both examined in the same sets of subjects. METHOD: Two-hundred forty subjects with CAD, 156 subjects with cardiovascular diseases without CAD, 279 subjects with Non Insulin Dependent Diabetes Mellitus (NIDDM) without CAD and 771 consecutive healthy newborn infants have been studied. RESULTS: The association of ACP1 and ADA1 with CAD depends on sex and diabetes. In particular, the association between ADA1 and CAD is present in nondiabetic subjects only, and it is dependent on sex (males), whereas the association of CAD with ACP1 is present in diabetic subjects only, and it is dependent on sex (females). CONCLUSIONS: The fact that the association of ACP1 with CAD is evident only in diabetic subjects, whereas the association of ADA1 with CAD is evident only in nondiabetic subjects suggests an heterogeneity in the pathogenetic mechanisms leading to CAD. In addition, the association with sex that could be based on hormonal differences is in favor of heterogenity. PMID- 20581656 TI - Hypokalemic thyrotoxic periodic paralysis with thyrotoxic psychosis and hypercapnic respiratory failure. AB - Thyrotoxic periodic paralysis is a rare and potentially lethal neuromuscular disease that manifests as recurrent episodic muscle weakness associated with hypokalemia and thyrotoxicosis. Paralysis can rarely involve respiratory muscles leading to acute respiratory failure. The disease primarily affects people of Asian descent, but it is being increasingly reported in other ethnic groups. We review the literature and report a case of hypokalemic thyrotoxic periodic paralysis manifesting as thyroid storm with episodic acute respiratory failure requiring recurrent intubation and eventually requiring thyroidectomy for resolution of symptoms. PMID- 20581657 TI - A phase I dose-escalation study of edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors. AB - Edotecarin (J-107088), a novel inhibitor of topoisomerase I has an additive effect on colon cell lines (HCT-116) when combined with 5-fluorouracil (5-FU). We conducted a phase I study to determine the maximum tolerated dose and recommended a phase II dose of edotecarin in combination with infusional 5-FU/leucovorin (LV) in patients with advanced solid tumors. Patients and cohorts of three to six patients were sequentially enrolled at progressively higher dose levels of edotecarin administered as a 1-h intravenous (IV) infusion every 2 weeks. The edotecarin starting dose was 6 mg/m, followed by 200 mg/m LV IV infusion administered over 2 h, then 400 mg/m bolus dose of 5-FU before the start of 2400 mg/m 5-FU continuous infusion for a further 46 h. Patients were evaluated for safety, pharmacokinetics, and tumor response according to the Response Evaluation Criteria in Solid Tumors criteria. Fourteen patients (10 male; four female) received a total of 90 cycles (range 3-18). Dose-limiting toxicities were observed in five of the 14 patients treated in the study. All dose-limiting toxicities were related to neutropenia. Only the 6 and 8 mg/m edotecarin dose levels were explored; however, no maximum tolerated dose was declared. One confirmed complete response in a patient with hepatocellular carcinoma and seven stable disease responses were achieved in the 14 treated patients. Pharmacokinetic analysis showed that edotecarin achieved and maintained apparent steady-state plasma concentrations during the IV administration in both the cycles. The administration of edotecarin in combination with infusional 5-FU/LV once every 14 days, even without the 5-FU bolus, did not permit adequate time for recovery from neutropenia. PMID- 20581658 TI - Cocaine reverses the changes in GABAA subunits and in glutamic acid decarboxylase isoenzymes mRNA expression induced by neonatal 6-hydroxydopamine. AB - Attention-deficit/hyperactivity disorder is related to altered functions in the dopaminergic and GABAergic pathways of cortical and subcortical brain areas The hyperactivity of attention-deficit/hyperactivity disorder is commonly modelled in rats after neonatal lesion with 6-hydroxydopamine (6-OHDA), and amphetamines are effective in reducing hyperactivity in this animal model. Our objectives were to evaluate whether cocaine reverses the motor hyperactivity of 6-OHDA-lesioned rats and to verify cocaine effects in altered mRNA expression of alpha2, alpha4, beta1 and beta2-GABAA subunits and GAD isoenzymes in the prefrontal cortex, hippocampus and striatum of 6-OHDA-lesioned rats. On PND4, 6-OHDA-lesioned or sham rats received 6-OHDA (100 microg intracisternal) or vehicle. Cocaine solution (0.1 mg/ml/day) was offered when adult for 23 days, using the two-bottle choice procedure. The subjects were evaluated in an open-field on the last day of cocaine treatment. 6-OHDA-lesioned rats showed increased locomotion and this hyperactivity was reversed during cocaine self-administration. 6-OHDA lesion caused an increase in the mRNA expression of GABAA subunits in specific brain areas and GAD isoenzymes in the hippocampus and striatum. Increased GAD65 and decreased GAD67 mRNA expression were also shown in the prefrontal cortex. Cocaine self-administration attenuated the effects of 6-OHDA lesions on the mRNA expression of alpha2-GABAA and beta2-GABAA subunits in the prefrontal cortex, reversed the mRNA expression of alpha2-GABAA subunits in the striatum and of alpha4-GABAA subunits in the prefrontal cortex and in the hippocampus, and reversed the mRNA expression of GAD65 and GAD67 in the brain areas studied. Our findings suggest that cocaine reverses some mRNA changes of GABAA subunits and GAD isoenzymes in reward circuits and the behavioural hyperactivity caused by 6 OHDA lesion. PMID- 20581659 TI - Immediate postpartum cardiorespiratory collapse: a management quandary. AB - A 35-year-old multiparous woman was found unresponsive, tachypnoeic, hypoxic and in shock 4 h postpartum. The ECG revealed S1 Q3 T3, a right bundle branch block pattern and right-axis deviation. The computed tomography of her pulmonary arteries revealed bilateral pulmonary artery thrombosis with dilated right ventricle. She was fibrinolyzed with intravenous Tenecteplase 30 mg bolus. Her saturation and tachypnoea improved and her ECG reverted to sinus rhythm subsequently. We discuss our use of off-label Tenecteplase in postpartum pulmonary embolism and review the literature. PMID- 20581660 TI - Dexamethasone inhibits immunoreactivity of dendritic cells in patients with chronic idiopathic thrombocytopenic purpura. AB - The objective of this study was to investigate the possible effects of dexamethasone treatment on the immunoreactivity of dendritic cells in patients with chronic idiopathic thrombocytopenic purpura (ITP). Thirty-six newly diagnosed patients with chronic ITP received an oral high dose of dexamethasone (HD-DXM) at single daily doses of 40 mg for 4 consecutive days. The CD14 leukocytes isolated from the 21 remission patients and 10 normal controls were stimulated by recombinant human granulocyte-macrophage colony-stimulating factor and rhIL-4. The surface antigens of the dendritic cells were analyzed by flow cytometry and the level of IL-12p70 in the supernatant was detected by enzyme linked immunosorbent assay. In ITP patients, the expression of both CD80 and CD86 in dendritic cells were significantly increased compared with those of the normal controls (51.60 +/- 13.47 vs. 36.03 +/- 15.43%, 61.50 +/- 15.93 vs. 40.28 +/- 11.49%, respectively; P < 0.05). After HD-DXM treatment, both CD80 and CD86 were decreased to levels comparable to normal controls (P > 0.05). The level of IL 12p70 in ITP patients was significantly higher (67.52 +/- 14.43 pg/ml) than the controls (39.78 +/- 10.03 pg/ml, P < 0.05). After treatment, IL-12p70 was reduced to 43.90 +/- 8.49 pg/ml with no significant differences between ITP group and control (P > 0.05). Dendritic cells and their cytokine secretion play important roles in ITP, and DXM may achieve its therapeutic effect on ITP by inhibiting immune responses through suppressing the function of dendritic cells. PMID- 20581661 TI - The c.-1639G>A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy. AB - A single nucleotide polymorphism c.-1639G>A in the promoter region of vitamin K epoxide reductase (VKORC1) gene has been found to account for most of the variability in response to oral vitamin K antagonist (VKA). Our aim was to study the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in a group of patients under stable anticoagulation, and to estimate the variability in response to VKA. We conducted a retrospective cohort analysis of 200 stable anticoagulation patients followed from the initiation of VKA. Out of 43 low-dose patients, 40 (93%) carried the A allele. The A allele was less frequent in the group of 30 patients requiring high VKA dose; among these patients 13 (43.3%) carried the A allele in the heterozygous form and none of them carried AA genotype. Patients with GG genotype required 2.6 times higher dose than patients carriers of AA genotype (P < 0.0001). Carriers of AA genotype were more likely to be overanticoagulated during follow-up after initiation of VKA when compared with carriers of the GA and GG genotypes (P < 0.0001). Patients with GG genotype spent more time below therapeutic range compared with patients carriers of AA (P = 0.0328) and GA genotype (P < 0.0001). VKORC1 c.-1639G>A polymorphism significantly influenced VKA dose and represented a good predictor of individuals predisposed to unstable anticoagulation. Pharmacogenetic testing could predict a high risk of overdose among 28.5% of our patients, carriers of AA genotype, before the initiation of anticoagulation. PMID- 20581662 TI - Anticoagulant activity of a dermatan sulfate from the skin of the shark Scyliorhinus canicula. AB - A dermatan sulfate isolated from the shark Scyliorhinus canicula skin by enzymatic digestion followed by purification with anion exchange chromatography was identified by chondroitinase and nitrous acid treatment and partially characterized by Fourier-transform infrared spectroscopy. Dermatan sulfate was the major glycosaminoglycan and represented 75% of the polysaccharide fraction in the sharkskin. This dermatan sulfate had a 38.6 kDa average molecular weight and 23% sulfate content. The anticoagulant action of this dermatan sulfate was checked by several coagulometric and colorimetric assays such as the activated partial thromboplastin time, thrombin time, thrombin generation and heparin cofactor II and antithrombin-mediated inhibition of thrombin and compared with that of porcine intestinal mucosa dermatan sulfate. The effects on platelet activation and aggregation were investigated using flow cytometry and aggregometry, respectively. The dermatan sulfate prolonged activated partial thromboplastin time and thrombin time, delayed and inhibited thrombin generation in a concentration-dependent manner. The specific anticoagulant activity of the sharkskin dermatan sulfate was 43 UI/mg. The anticoagulant effect of sharkskin dermatan sulfate was higher than that of the porcine dermatan sulfate and was due to the potentiation of thrombin inhibition by heparin cofactor II. Moreover, it had no effect on platelet aggregation and activation induced by various agonists and thereby constitutes a potentially useful drug of interest in anticoagulant therapy. PMID- 20581663 TI - Factor VIIa analog has marked effects on platelet function and clot kinetics in blood from patients with hemophilia A. AB - To evaluate the hemostatic effects of NN1731 and rFVIIa, an ex-vivo study in hemophilia patients used the Hemodyne Hemostasis Analysis System (HAS) to measure platelet contractile force (PCF), clot elastic modulus (CEM), and force onset time (FOT), and the Haemoscope Thrombelastograph (TEG) to measure reaction time (R), kinetics time (K), and maximum amplitude (MA). Blood samples from 10 healthy volunteers and 10 Factor VIII-deficient patients of varying severity (mild, moderate, severe), were spiked with rFVIIa and NN1731 (both 0.64 and 1.28 microg/ml, respectively) and analyzed to characterize platelet function and clot kinetics. There was wide variability in the rFVIIa response. NN1731 had greater and more consistent effects on PCF, CEM, FOT, R, and K relative to rFVIIa, in all hemophilia groups. The lowest NN1731 concentration (0.64 microg/ml) shortened R and FOT, and increased CEM and PCF more than rFVIIa 1.28 microg/ml. NN1731 normalized clotting parameters equivalent to values obtained in healthy volunteers. FOT and R were highly correlated (r = 0.96). No correlation was observed between CEM and MA. NN1731 produced less variable, more pronounced and predictable ex-vivo hemostatic effects on PCF, CEM, FOT, R and K than rFVIIa in all hemophilia groups. HAS and TEG assays provided similar estimates of FOT and R, however CEM appeared to be more sensitive than MA to changes in clot firmness. PMID- 20581664 TI - Thrombophilia and the risk of thromboembolic events in women on oral contraceptives and hormone replacement therapy. AB - Thrombophilia contributes to the risk of thrombosis in women using female hormones. The objective of the present study was to evaluate the prevalence of thrombophilia in women with thromboembolic events (TEEs) using oral contraceptives or hormone replacement therapy (HRT) and assess the contribution of a family history and the duration of hormone use in predicting thrombosis. A retrospective analysis was performed of the case records of women who developed a TEE while on oral contraceptives or HRT and were referred for thrombophilia evaluation over a 4-year period. Among 85 women who developed a TEE while on oral contraceptives or HRT, 65 had at least one additional thrombophilia risk factor. Of the 85 cases, 23 tested positive for more than two thrombophilias, 16 had factor V Leiden, five had the prothrombin gene G20210A polymorphism, 26 had antiphospholipid antibodies, 10 had elevated homocysteine, four had protein C deficiency, and seven had protein S deficiency. There were 64 TEE: 16 pulmonary emboli, 17 cerebrovascular events, 11 intra-abdominal thromboses, 13 deep venous thromboses, five cases of superficial thrombophlebitis, and two retinal vein thromboses. Of the 65 women, 37% had a positive family history of thrombosis. Approximately half of the women had been taking oral contraceptives or HRT for more than 1 year. There is a high prevalence of thrombophilia in women who developed a TEE while using oral contraceptives or HRT for more than 1 year. Family and personal history of thrombosis should be carefully evaluated in all women before initiating or continuing oral contraceptives or HRT, and a positive history may warrant a thrombophilia screening. PMID- 20581665 TI - The evaluation of interaction between red blood cells in blood coagulation by optical tweezers. AB - To maintain the life of patients with hemophilia, apoplexy or hemorrhage, appropriate blood coagulation is crucial. To study the microscopic phenomena of blood coagulation and the therapeutic effects of blood medication, optical tweezers were applied to estimate the interaction between red blood cells in the coagulation process. By measuring minimum optical power required to trap the coagulating blood cells, the pN-scale interaction between them can be evaluated. In normal blood sample, the interaction rises in accordance with coagulation time. The addition of heparin attenuates the interaction and postpones the coagulation, whereas the addition of tranexamic acid starts the coagulation early at the beginning and allows the process completed in less time. PMID- 20581666 TI - Ratio of angiopoietin-2 to angiopoietin-1 as a predictor of mortality in acute lung injury patients. AB - OBJECTIVE: To test the hypothesis that the concentration of angiopoietin-2 relative to angiopoietin-1 may be a useful biological marker of mortality in acute lung injury patients. We also tested the association of concentration of angiopoietin-2 relative to angiopoietin-1 with physiologic and biological markers of activated endothelium. DESIGN: Prospective, observational cohort study. SETTING: Intensive care units in a tertiary care university hospital and a university-affiliated city hospital. PATIENTS: Fifty-six mechanically ventilated patients with acute lung injury. INTERVENTIONS: Baseline plasma samples and pulmonary dead-space fraction measurements were collected within 48 hrs of acute lung injury diagnosis. MEASUREMENTS AND MAIN RESULTS: Plasma levels of angiopoietin-1 and angiopoietin-2 and of biomarkers of endothelial activation were measured by enzyme-linked immunosorbent assay. Baseline concentration of angiopoietin-2 relative to angiopoietin-1 was significantly higher in patients who died (median, 58 [interquartile range, 17-117] vs. 14 [interquartile range, 6 35]; p = .01). In a multivariable analysis stratified by dead-space fraction, concentration of angiopoietin-2 relative to angiopoietin-1 was an independent predictor of death, with an adjusted odds ratio of 4.3 (95% confidence interval, 1.3-13.5; p = .01) in those with an elevated pulmonary dead-space fraction (p = .03 for interaction between pulmonary dead-space fraction and concentration of angiopoietin-2 relative to angiopoietin-1). Moderate to weak correlation was found with biological markers of endothelial activation. CONCLUSIONS: The ratio of concentration of angiopoietin-2 relative to angiopoietin-1 may be a prognostic biomarker of endothelial activation in acute lung injury patients and, along with pulmonary dead-space fraction, may be useful for risk stratification of acute lung injury patients, particularly in identifying subgroups for future research and therapeutic trials. PMID- 20581667 TI - Validity and reliability of an intuitive conscious sedation scoring tool: the nursing instrument for the communication of sedation. AB - OBJECTIVE: To develop a symmetrical 7-level scale (+3, "dangerously agitated" to 3, "deeply sedated") that is both intuitive and easy to use, the Nursing Instrument for the Communication of Sedation (NICS). DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: Mixed surgical, medical intensive care unit (ICU) population. INTERVENTIONS: Patient assessment. MEASUREMENTS AND MAIN RESULTS: Criterion, construct, face validity, and interrater reliability of NICS over time and comparison of ease of use and nursing preference between NICS and four common intensive care unit sedation scales. A total of 395 observations were performed in 104 patients (20 intubated [INT], 84 non intubated) by 59 intensive care unit providers. Criterion validity was tested comparing NICS WITH the 8-point level of arousal scale, demonstrating excellent correlation (rs = .96 overall, .95 non intubated, 0.85 intubated, all p < .001). Construct validity was confirmed by comparing NICS with the Richmond Agitation-Sedation Scale, demonstrating excellent correlation (rs = .98, p < .001). Face validity was determined in a blinded survey of 53 intensive care unit nurses evaluating NICS and four other sedation scales. NICS was highly rated as easy to score, intuitive, and a clinically relevant measure of sedation, and agitation and was preferred overall (74% NICS, 17% Richmond Agitation-Sedation Scale, 11% Other, p < .001 NICS vs. Richmond Agitation-Sedation Scale). Interrater reliability was assessed, using the five scales at three timed intervals, during which 37% of patients received sedative medication. The mean NICS score consistently correlated with each of the other scales over time with an rs of >.9. Using the intraclass correlation coefficient as a measure of Interrater reliability, NICS scored as high, or higher than Richmond Agitation Sedation Scale, Riker Sedation-Agitation Scale, Motor Activity Assessment Scale, or Ramsay over the three time periods. CONCLUSION: NICS is a valid and reliable sedation scale for use in a mixed population of intensive care unit patients. NICS ranked highest in nursing preference and ease of communication and may thus permit more effective and interactive management of sedation. PMID- 20581668 TI - Recent advances in leprosy and Buruli ulcer (Mycobacterium ulcerans infection). AB - PURPOSE OF REVIEW: After tuberculosis, leprosy (Mycobacterium leprae) and Buruli ulcer (M. ulcerans infection) are the second and third most common mycobacterial infections in humankind, respectively. Recent advances in both diseases are summarized. RECENT FINDINGS: Leprosy remains a public health problem in some countries, and new case detections indicate active transmission. Newly identified M. lepromatosis, closely related to M. leprae, may cause disseminated leprosy in some regions. In genome-wide screening in China, leprosy susceptibility associates with polymorphisms in seven genes, many involved with innate immunity. World Health Organization multiple drug therapy administered for 1 or 2 years effectively arrests disseminated leprosy but disability remains a public health concern. Relapse is infrequent, often associated with higher pretreatment M. leprae burdens. M. ulcerans, a re-emerging environmental organism, arose from M. marinum and acquired a virulence plasmid coding for mycolactone, a necrotizing, immunosuppressive toxin. Geographically, there are multiple strains of M. ulcerans, with variable pathogenicity and immunogenicity. Molecular epidemiology is describing M. ulcerans evolution and genotypic variants. First-line therapy for Buruli ulcer is rifampin + streptomycin, sometimes with surgery, but improved regimens are needed. SUMMARY: Leprosy and Buruli ulcer are important infections with significant public health implications. Modern research is providing new insights into molecular epidemiology and pathogenesis, boding well for improved control strategies. PMID- 20581669 TI - Dengue and chikungunya infections in travelers. AB - PURPOSE OF REVIEW: Dengue and chikungunya are arboviruses that have caused major outbreaks and infected travelers, and both can be associated with fever and rash. We review the recent epidemiology of dengue and chikungunya infections and discuss their clinical presentations, diagnosis, treatment, and prevention. We highlight the findings in travelers. RECENT FINDINGS: Globally dengue is one of the most common infections associated with travel, and incidence has increased in the Americas in recent years, especially in Brazil. Chikungunya has caused dramatic outbreaks in the Indian Ocean islands since 2004, and has spread to south and south-east Asia. Dengue virus and chikungunya virus also possess the potential to cause autochthonous transmission in temperate regions of developed countries due to the presence of the vector mosquito, Aedes albopictus. Such an outbreak (chikungunya infection) did occur in 2007 in Italy. A mutation in chikungunya virus (A226V) appears to improve virus survival in Aedes albopictus and also increase its virulence. SUMMARY: The findings assist in differentiating dengue and chikungunya from other acute febrile illnesses and from each other. The findings also illustrate potential outbreaks in nonendemic countries, important toward developing control and prevention strategies. PMID- 20581670 TI - Japanese encephalitis: update on vaccines and vaccine recommendations. AB - PURPOSE OF REVIEW: Japanese encephalitis is the most common vaccine-preventable viral encephalitis in Asia. In view of the production cessation of the inactivated mouse brain-derived Japanese encephalitis vaccine, it is timely to provide an update on new Japanese encephalitis vaccines and revised vaccine recommendations. RECENT FINDINGS: A new inactivated, adjuvanted, Vero cell culture-based Japanese encephalitis vaccine, IC51, was licensed in Europe and the United States in 2009. Administered in a two-dose regimen at 0 and 28 days, it was shown to be well tolerated and produce high seroconversion rates. In addition, Chimerivax Japanese encephalitis, a novel live-attenuated one-dose chimeric vaccine comprising the structural genes of SA 14-14-2 virus and nonstructural genes of yellow fever 17D virus, is in the process of getting licensed in Australia and in south east Asia. SUMMARY: Previous recommendations for Japanese encephalitis vaccination of travelers were predicated on minimizing exposure to a mouse-brain-derived vaccine with a poorly understood and worrisome safety profile, whereas the risk of acquiring Japanese encephalitis itself during travel was assessed to be relatively low. With the availability of a new cell culture-derived vaccine IC51 with an excellent safety profile, it is appropriate to reconsider benefit-risk considerations for the vaccination of travelers. These considerations are reflected in the March 2010 revised recommendations by the United States Advisory Committee on Immunization Practices. PMID- 20581671 TI - Influenza, including the novel H1N1, in organ transplant patients. AB - PURPOSE OF REVIEW: This article will review the epidemiology, diagnosis, prevention and management of influenza in solid organ transplant recipients. RECENT FINDINGS: A number of recent studies have documented that influenza vaccination is both well tolerated and generally effective in producing an immunologic response in most solid organ transplant (SOT) recipients. Antiviral use is associated with improved clinical outcomes, but prolonged shedding may require a longer course of therapy than what is currently approved by the FDA. Antiviral resistance emerges rarely in transplant patients and should be considered in all patients with an inadequate clinical and/or virologic response. SUMMARY: Influenza is associated with significant morbidity and mortality, particularly in lung transplant recipients. Molecular diagnostics are preferred over other diagnostic modalities, if available. Influenza vaccination is well tolerated and provides protective benefit in most SOT recipients; in those with contraindications to vaccination or in whom responses are predicted to be poor, antivirals may be considered. Antiviral therapy is associated with improved outcomes in transplant patients and treatment should be continued until clinically and virologic response have been documented. Resistance, particularly with patients infected with the pandemic influenza A/H1N1, should be considered and treated with an antiviral with predicted activity. PMID- 20581673 TI - How to stem the tide of carbapenemase-producing enterobacteriaceae?: proactive versus reactive strategies. AB - PURPOSE OF REVIEW: The spread of carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae in healthcare settings is an important medical problem and a major public health threat. Infections with CRE are associated with high rates of morbidity and mortality, and are spreading rapidly across the globe. The medical community can either observe the natural course of this epidemic or act proactively and take adequate preventive measures to contain the spread of these bacteria. The purpose of this review is to highlight the impact of these problematic pathogens and to examine infection control policies needed in order to limit their spread. RECENT FINDINGS: The incidence of CRE is on the rise in several parts of the world; however, data regarding proper infection control methods on this issue are scarce. Great variability exists in infection control measures taken to confront CRE in various settings. Recently, two sets of guidelines to control CRE have been issued, one by the US Centers for Disease Control and Prevention and the other by an expert group under the auspices of the European Society of Clinical Microbiology and Infectious Diseases. These guidelines have many similarities but also considerable differences. SUMMARY: Whereas clinical information regarding how to contain infections by CRE pathogens is still limited, it is obvious that it relies on a multifaceted approach and implementation of strict infection control measures. Since it has been observed that lack of adequate and timely reaction is common and associated with great morbidity and mortality, preparation plans should be evaluated and implemented locally, regionally, nationally and even on an international level. PMID- 20581672 TI - Adult-onset presentations of genetic immunodeficiencies: genes can throw slow curves. AB - PURPOSE OF REVIEW: The molecular and genetic mechanisms behind adult presentations of primary immunodeficiency diseases are examined, with particular emphasis on cases where this was heralded by severe, recurrent, or opportunistic infection. RECENT FINDINGS: A detailed analysis over the last two decades of the relationship between genotype and clinical phenotype for a number of genetic immunodeficiencies has revealed multiple mechanisms that can account for the delayed presentation of genetic disorders that typically present in childhood, including hypomorphic gene mutations and X-linked gene mutations with age-related skewing in random X-chromosome inactivation. Adult-onset presentations of chronic granulomatous disease, X-linked agammaglobulinemia, IL-12/Th1/IFN-gamma and IL 23/Th17/IL-17 pathway defects, and X-linked lymphoproliferative disorder are used to illustrate these mechanisms. Finally, certain genetic types of common variable immunodeficiency are used to illustrate that inherited null mutations can take decades to manifest immunologically. SUMMARY: Both genetic mechanisms and environmental factors can account for adult-onset infectious and noninfectious complications as manifestations of disorders that are typically present in childhood. This emphasizes the potential complexity in the relationship between genotype and phenotype with natural human mutations. PMID- 20581674 TI - Multiresistant Acinetobacter baumannii infections: epidemiology and management. AB - PURPOSE OF REVIEW: We present recent data about epidemiology of Acinetobacter baumannii in the hospital setting, major resistance mechanisms, and therapeutic options for infections caused by multidrug-resistant strains. RECENT FINDINGS: A. baumannii has emerged as a major cause of healthcare-associated infections. It commonly presents resistance to multiple antimicrobial agents, including carbapenems. These strains are now ussually resistant to the rest of antipseudomonal beta-lactams and sulbactam, a beta-lactamase inhibitor with bactericide activity against A. baumannii. Rifampicin has demonstrated its effectiveness in animal models but can never be used in monotherapy because of the rapid development of resistance. Colistin, an old antibiotic, has re-emerged as a valid alternative given its excellent in-vitro activity. Numerous studies have confirmed its efficacy in serious infections, including ventilator associated pneumonia and nosocomial meningitis, with an acceptable safety profile. Tigecycline appears as a promising therapeutic option for multidrug resistant A. baumannii, althogh more clinical data about its efficacy especially in pulmonary infections are required. The role of combination therapy or the use or colistin in alternative routes (nebulized or intrathecally) has not been established. SUMMARY: The optimal treatment for multidrug-resistant A. baumannii nosocomial infections has not been established. Carbapenems are the mainstay of treatment in susceptible isolates. Colistin and tigecycline retain good in-vitro activity and in many cases represent the only therapeutic options. PMID- 20581675 TI - The effectiveness of national guidelines for preventing cardiovascular disease: integrating effectiveness concepts and evaluating guidelines' use in the real world. AB - PURPOSE OF REVIEW: Clinical guidelines historically have emphasized efficacy (intervention benefit in a controlled or experimental setting) rather than effectiveness (intervention benefit in the real world). This review examines how concepts of effectiveness currently influence the development of guidelines for prevention of cardiovascular disease, and how these concepts contribute to increased evaluation of guideline effectiveness. RECENT FINDINGS: A growing emphasis on effectiveness in cardiovascular preventive guidelines is largely influenced by a desire for guidelines to facilitate improved quality of care. Single risk factor guidelines for cardiovascular disease are being merged, and guideline recommendations are becoming simpler and easier to implement into practice. Simultaneously, guideline programs are undertaking a wider range of development, implementation and evaluation activities. Implementation science, a supporting discipline, is rapidly maturing and resulting in increasingly sophisticated studies designed to test the effectiveness of prevention interventions and approaches to improve guideline uptake. Modelling studies are used to develop effective guideline recommendations and evaluate the overall effectiveness of guidelines for reducing cardiovascular disease. SUMMARY: A sea change is occurring in cardiovascular guidelines toward effectiveness and prevention of multiple chronic diseases, and away from a focus on the efficacy of medical therapy for individual cardiovascular disease risk factors. The 'effectiveness sea' should eventually stretch to embrace cost-effectiveness and population effectiveness. PMID- 20581676 TI - The effects of statins on skeletal muscle strength and exercise performance. AB - PURPOSE OF REVIEW: HMG-CoA reductase inhibitors or statins are associated with a variety of muscle side-effects but little is known about the effect of statins on skeletal muscle strength and exercise performance. We performed a literature search to examine these issues. RECENT FINDINGS: We identified six studies examining the effect of statins on muscle strength and nine studies examining their effect on exercise tolerance. In general, studies examining both issues were small and used crude measures of strength and exercise performance. SUMMARY: There is insufficient data to determine if statins affect muscle strength and exercise performance. There is suggestive evidence that these drugs may reduce muscle strength in older patients and alter energy metabolism during aerobic exercise, both possibilities require further study. PMID- 20581677 TI - Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities. AB - Oxidative stress, an emerging risk factor for premature atherosclerosis and cardiovascular disease, mediates the formation of proinflammatory, pro atherogenic oxidized low-density lipoprotein (oxLDL) in the arterial intima. Circulating HDL particles, and particularly small, dense, protein-rich HDL3, may provide potent protection of LDL in vivo from oxidative damage by free radicals in the arterial intima, resulting in the inhibition of the generation of proinflammatory oxidized lipids, primarily lipid hydroperoxides (LOOH) but also short-chain oxidized phospholipids (oxPL). HDL-mediated inactivation of LOOH involves initial transfer of phospholipid hydroperoxides (PLOOH) from LDL to HDL3, which is governed by the rigidity of the surface monolayer of HDL, and subsequent reduction of PLOOH by redox-active Met residues of apolipoprotein A-I (apoA-I) with the formation of phospholipid hydroxides (PLOH) and methionine sulphoxides. HDL-associated enzymes may in turn contribute to the hydrolytic inactivation of short-chain oxPL. Mounting evidence suggests that the integrated antioxidative activity of HDL appear to be defective in atherogenic dyslipidaemias involving low HDL-cholesterol levels; anomalies in the proteome and lipidome of HDL particles in dyslipidaemic patients may underlie such functional deficiency. Pharmacological normalization of HDL metabolism concomitantly with correction of circulating levels, composition and biological activities of HDL particles, with enrichment in apoA-I and reduction in HDL surface rigidity, may constitute an efficacious therapeutic approach to attenuate atherosclerosis in dyslipidaemic patients at high cardiovascular risk. PMID- 20581678 TI - Recent insights into fatty liver, metabolic dyslipidaemia and their links to insulin resistance. AB - PURPOSE OF REVIEW: To summarize recent research into the mechanisms linking insulin resistance, nonalcoholic fatty liver disease and metabolic dyslipidaemia. RECENT FINDINGS: Pathologically increased nonesterified fatty acids have widely been viewed as a key driver of hepatic insulin resistance/nonalcoholic fatty liver disease/metabolic dyslipidaemia. However, this may have been overestimated, and growing evidence now also implicates dysregulated hepatic de-novo lipogenesis in the pathogenesis of these phenomena. This is driven by the action of hyperinsulinaemia on the liver, mediated by PI3 kinase, though consensus on the downstream effectors remains to be reached. Endoplasmic reticulum stress and/or components of the attendant unfolded protein response have also emerged as players in dysregulated hepatic metabolism due to nutritional overload. Several points of convergence between metabolic and unfolded protein response pathways have been described, notably centring on the transcription factor XBP1. SUMMARY: Insulin resistance, nonalcoholic fatty liver disease and metabolic dyslipidaemia are inextricably linked and need to be considered together. Modelling and dissecting prevalent forms of the disease is complex, but unrestrained de-novo lipogenesis driven by hyperinsulinaemia appears to play an important role. Endoplasmic reticulum stress and the associated unfolded protein response may also contribute to cellular mismatch between triglyceride secretion/metabolism and synthesis, though a complete picture has yet to emerge. PMID- 20581679 TI - Do structural differences in statins correlate with clinical efficacy? AB - PURPOSE OF REVIEW: Statins, by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decrease the synthesis not only of cholesterol but also of nonsteroidal mevalonate derivatives. While the first effect translates into plasma cholesterol reductions, the second is related to nonlipid-lowering (pleiotropic) properties. Purpose of this review is to assess the correlation between differences in statin structures and clinical effects. While the cardiovascular benefits of statin chronic therapy are achieved by lowering low density lipoprotein cholesterol (LDL-C) and should be considered a class effect, the acute ones may reflect structure differences and pleiotropic properties of these drugs. RECENT FINDINGS: Clinical studies conducted in acute coronary syndrome patients suggest that some benefits achieved by early statin treatment could be related to their pleiotropic properties. Indeed, ex-vivo studies showed the ability of sera from hypercholesterolemic patients treated with a single dose of atorvastatin (but not of simvastatin), to inhibit smooth muscle cell proliferation, independently of LDL-C lowering. SUMMARY: These findings give a clinical ground to statins' potentially structure-related anti-inflammatory and pleiotropic properties, opening the possibility to control different aspects of atherosclerosis, by choosing the appropriate statin (tailored therapy), particularly in high-cardiovascular-risk patients. PMID- 20581680 TI - Acquired myasthenia gravis in childhood. AB - PURPOSE OF REVIEW: This review discusses recent studies on myasthenia gravis with onset in childhood (juvenile myasthenia gravis) and neonatal myasthenia gravis. RECENT FINDINGS: The occurrence of myasthenia gravis in childhood is strongly influenced by genetic and environmental factors. Juvenile myasthenia gravis is associated with antibodies to the acetylcholine receptor (AChR) in most patients. Thymoma is rare, but often malignant in children. The frequency of juvenile myasthenia gravis with antibodies to the muscle-specific kinase (MuSK) varies markedly in different countries; some distinct features have been described. Management of juvenile myasthenia gravis does not differ, on the whole, from that of adult myasthenia gravis. Timing of thymectomy in young children is still controversial. Maternal antifetal type AChR antibodies can cause persistent focal weakness in the offspring, while neonatal myasthenia gravis associated with MuSK antibodies is often a severe and protracted albeit transient disease. SUMMARY: Juvenile myasthenia gravis, like its adult-onset counterpart, is a heterogeneous disease. Clinical presentation is influenced by antibody status, ethnicity and age of onset. Treatment is very effective, but guidelines and controlled trials are needed.The risk for neonatal myasthenia gravis appears to be markedly influenced by maternal antibody subclass and antigen specificity. Adequate treatment in mothers can reduce both frequency and severity of neonatal disease. PMID- 20581681 TI - Iatrogenic myopathies. AB - PURPOSE OF REVIEW: This review summarizes the recent progress in understanding of myopathies induced by therapeutic agents, the underlying pathogenetic mechanisms and the management of iatrogenic muscle disorders, focussing on statin-associated myopathies. RECENT FINDINGS: Recent reports from observational studies have provided further information on the frequency of statin-associated myalgia and myopathy, which is the most important group of iatrogenic muscle disorders in current clinical practice, and on the relative myotoxicity of different statins and interactions with other therapeutic agents. However, there is still a need for further prospective studies with more clearly defined diagnostic criteria for statin myopathy and comparative studies of patient cohorts treated with different statins to determine the true incidence of myopathy as an adverse effect. Other important advances include recognition that genetic variants and mutations in the SLCO1B1, CYP and COQ2 genes may determine individual susceptibility to statin myopathy, and that statins may also initiate immune-mediated forms of necrotizing and inflammatory myopathy and unmask or aggravate various metabolic myopathies and other neuromuscular disorders. SUMMARY: Recent reports have broadened the spectrum of iatrogenic myopathies and neuromuscular disorders associated with statins, and have thrown further light on the role of genetic predisposing factors, the mechanisms of myotoxicity and the management of such cases. PMID- 20581682 TI - Advances in functional imaging of the human cerebellum. AB - PURPOSE OF REVIEW: A quarter century of functional neuroimaging has provided a number of insights into the function of the human cerebellum. However, progress has been relatively slow, partly because cerebellar imaging poses a number of unique challenges for functional magnetic resonance imaging (fMRI). This review provides a guide to problems and recent solutions in the design, analysis and interpretation of neuroimaging studies of the human cerebellum. RECENT FINDINGS: One major problem in the interpretation of functional imaging studies is that it is still unclear what type of neural activity is reflected in the cerebellar blood-oxygenation-level-dependent signal. We summarize recent work that has provided partly contradictory insights. We then highlight some technical challenges, specifically the susceptibility to physiological artifacts, and recently developed techniques to account for them. Furthermore, the small size and functional heterogeneity of the cerebellum poses a challenge for normalization and atlas methods, which demands different analysis techniques than those used in the neocortex. Finally, we highlight some novel results assessing anatomical and functional connectivity with the neocortex. SUMMARY: Although these results clearly show the limitations of current approaches, they also show the potential of anatomical and functional MRI for the study of the human cerebellum. PMID- 20581683 TI - Update in restless legs syndrome. AB - PURPOSE OF REVIEW: Although restless legs syndrome (RLS) is a disorder recognized in the medical literature since the 17th century, there have only recently been significant clinical and scientific advances in diagnosis, epidemiology and understanding the disorder, mainly due to the advent of dopaminergic treatment. RECENT FINDINGS: Recent discoveries have uncovered the iron-dopamine connection in RLS and the basic dopaminergic pathology related to the RLS symptoms. These have led to new understanding of the morbidity of RLS and the many conditions associated with RLS, which have also supported new approaches to treatment. These developments are each briefly described here. SUMMARY: Although there has been progress in understanding, diagnosing and treating RLS, it remains an underdiagnosed and undertreated condition severely impairing functioning of patients with moderate-to-severe disease. Much work is needed to improve on current, as well as other novel therapies. PMID- 20581685 TI - Behavioural relevance of variation in white matter microstructure. AB - PURPOSE OF REVIEW: There has been a rapid increase in studies using diffusion weighted magnetic resonance imaging (DWI) to interrogate white matter structure in the human brain. This review considers the evidence that interindividual variation in white matter structure is behaviourally relevant. RECENT FINDINGS: Maturation or deterioration of white matter throughout the lifespan relates to development or decline in specific cognitive skills. In addition, age-independent relationships between white matter anatomy and ability are found in healthy adult populations. Such relationships may in part be determined by genetics but can also be driven by experience. SUMMARY: Individual differences in white matter anatomy, visible using DWI, have consequences for behaviour. The discovery of such relationships highlights the potential for identification of imaging biomarkers that could predict how well patients will respond to specific interventions. PMID- 20581686 TI - Graph theoretical modeling of brain connectivity. AB - PURPOSE OF REVIEW: In recent years, there has been an explosion of studies on network modeling of brain connectivity. This review will focus mainly on recent findings concerning graph theoretical analysis of human brain networks with a variety of imaging modalities, including structural MRI, diffusion MRI, functional MRI, and EEG/MEG. RECENT FINDINGS: Recent studies have utilized graph theoretical approaches to investigate the organizational principles of brain networks. These studies have consistently shown many important statistical properties underlying the topological organization of the human brain, including modularity, small-worldness, and the existence of highly connected network hubs. Importantly, these quantifiable network properties were found to change during normal development, aging, and various neurological and neuropsychiatric diseases such as Alzheimer's disease and schizophrenia. Moreover, several studies have also suggested that these network properties correlate with behavioral and genetic factors. SUMMARY: The exciting research regarding graph theoretical analysis of brain connectivity yields truly integrative and comprehensive descriptions of the structural and functional organization of the human brain, which provides important implications for health and disease. Future research will most likely involve integrative models of brain structural and functional connectivity with multimodal neuroimaging data, exploring whether graph-based brain network analysis could yield reliable biomarkers for disease diagnosis and treatment. PMID- 20581684 TI - Imaging genomics. AB - PURPOSE OF REVIEW: Imaging genomics is an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease. Worldwide, thousands of individuals are being scanned with high-throughput genotyping (genome-wide scans), and new imaging techniques [high angular resolution diffusion imaging and resting state functional magnetic resonance imaging (MRI)] that provide fine-grained measures of the brain's structural and functional connectivity. Along with clinical diagnosis and cognitive testing, brain imaging offers highly reproducible measures that can be subjected to genetic analysis. RECENT FINDINGS: Recent studies of twin, pedigree, and population-based datasets have discovered several candidate genes that consistently show small to moderate effects on brain measures. Many studies measure single phenotypes from the images, such as hippocampal volume, but voxel wise genomic methods can plot the profile of genetic association at each 3D point in the brain. This exploits the full arsenal of imaging statistics to discover and replicate gene effects. SUMMARY: Imaging genomics efforts worldwide are now working together to discover and replicate many promising leads. By studying brain phenotypes closer to causative gene action, larger gene effects are detectable with realistic sample sizes obtainable from meta-analysis of smaller studies. Imaging genomics has broad applications to dementia, mental illness, and public health. PMID- 20581687 TI - Pioglitazone in chemically induced mammary carcinogenesis in rats. AB - Data available from in-vitro and in-vivo studies suggest oncostatic properties of peroral antidiabetics, thiazolidinediones, in many types of cancer. This study is the first report on the chemopreventive effect of pioglitazone in mammary carcinogenesis in rats. Mammary carcinogenesis was induced by N-methyl-N nitrosourea administered in two intraperitoneal doses per 50 mg/kg bodyweight on the 43rd and 50th postnatal days. Pioglitazone was administered in the diet at concentrations of 10 and 100 ppm, respectively, 12 days before the first carcinogen dose until the termination of the experiment. During the experiment, the animals were weighed weekly and palpated for the presence of mammary tumors, and the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 17 weeks after the first carcinogen dose; basic tumor growth parameters and metabolic and hormonal variables were evaluated. Pioglitazone at higher concentration decreased incidence and frequency per group from the 11th week of experiment when compared with the control group and a group receiving a lower dose. Pioglitazone at a higher dose decreased the final incidence by 38%, frequency per group by 63%, and extended latency period by 32% when compared with the control group. Our data suggest that pioglitazone and other glitazones should be further investigated for oncopreventive effects. PMID- 20581688 TI - The impact of kidney function at highly active antiretroviral therapy initiation on mortality in HIV-infected women. AB - BACKGROUND: In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease remains a predictor of death after HAART initiation. METHODS: To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study. Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006. RESULTS: Chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history, and CD4 cell count (hazard ratio 2.23, 95% confidence interval: 1.45 3.43). Adjustment for hypertension and diabetes history attenuated this association (hazard ratio = 1.89, confidence interval: 0.94-3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (hazard ratio = 1.09, confidence interval: 1.00-1.19, per 20% decrease in estimated glomerular filtration rate). CONCLUSIONS: Kidney function at HAART initiation remains an independent predictor of death in HIV infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with chronic kidney disease in HIV-infected persons. PMID- 20581689 TI - Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. AB - OBJECTIVE: To determine the association of inflammatory markers, fibrinogen, and C-reactive protein (CRP), with 5-year mortality risk. METHODS: Vital status was ascertained in 922 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. Multivariable logistic regression estimated odds ratios after adjustment for demographic, cardiovascular, and HIV related factors. RESULTS: Over a 5-year period, HIV-infected participants with fibrinogen levels in the highest tertile (>406 mg/dL) had 2.6-fold higher adjusted odds of death than those with fibrinogen in the lowest tertile (<319 mg/dL). Those with high CRP (>3 mg/L) had 2.7-fold higher adjusted odds of death than those with CRP <1 mg/L. When stratified by CD4 count category, fibrinogen (as a linear variable) remained independently associated [odds ratio (95% confidence intervals)] per 100 mg/dL increase in fibrinogen: 1.93 (1.57 to 2.37); 1.43 (1.14 to 1.79); 1.43 (1.14 to 1.81); and 1.30 (1.04 to 1.63) for CD4 <200, 200-350, >350 to 500, and >500 cells per microliter, respectively. Higher CRP also remained associated with higher odds of death overall and within each CD4 subgroup. CONCLUSIONS: Fibrinogen and CRP are strong and independent predictors of mortality in HIV-infected adults. Our findings suggest that even in those with relatively preserved CD4 counts >500 cells per microliter, inflammation remains an important risk factor for mortality. Further investigation should determine whether interventions to reduce inflammation might decrease mortality risk in HIV infected individuals. PMID- 20581691 TI - Tinnitus in fourth nerve palsy: an indicator for an intra-axial lesion. AB - Accompanying neurological symptoms and signs are diagnostic hallmarks of fourth nerve palsy (4NP) from an intra-axial lesion. Due to the proximity of the trochlear nucleus and fascicles to the inferior colliculus (IC), auditory symptoms including tinnitus may occur with an intra-axial 4NP. A 53-year-old man with hypertension and diabetes developed right 4NP with a sudden worsening of tinnitus. MRI disclosed an infarction involving the trochlear fascicle and IC in the left dorsal midbrain. Tinnitus may be a symptom indicating an intra-axial lesion causing a 4NP. PMID- 20581692 TI - Photo essay. MRI and positron emission tomography findings in Heidenhain variant Creutzfeldt-Jakob disease. AB - The typical presentation of Heidenhain variant Creutzfeldt-Jakob disease (CJD) is a rapidly progressive visual loss in the setting of a relatively normal ophthalmologic examination. At presentation, patients with this uniformly fatal illness frequently demonstrate only minor cortical abnormalities on MRI. Here, we document the clinical presentation and imaging results of a patient with Heidenhain variant CJD in whom abnormalities on positron emission tomographic imaging were more evident than changes on MRI. These changes were present in striate cortex and visual association areas, providing clinical-anatomical correlation with our patient's visual deficits. Nuclear imaging provides a considerably more sensitive measure of neural dysfunction early in the course of this disease. PMID- 20581690 TI - Anti-influenza serum and mucosal antibody responses after administration of live attenuated or inactivated influenza vaccines to HIV-infected children. AB - BACKGROUND: Live-attenuated influenza vaccine (LAIV) prevents more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the antibody responses to LAIV or TIV in HIV-infected children. METHODS: Blood and saliva obtained at enrollment, 4 and 24 weeks postimmunization from 243 HIV-infected children randomly assigned to TIV or LAIV were analyzed. RESULTS: Both vaccines increased the anti-influenza neutralizing antibodies at 4 and 24 weeks postimmunization. At 4 weeks postimmunization, TIV recipients had 2-fold to 3-fold higher neutralizing antibody titers than LAIV recipients, but the proportions of subjects with protective titers (>= 1:40) were similar between treatment groups (96%-100% for influenza A and 81%-88% for influenza B). Both vaccines increased salivary homotypic IgG antibodies, but not IgA antibodies. Both vaccines also increased serum heterosubtypic antibodies. Among HIV-specific characteristics, the baseline viral load correlated best with the antibody responses to either vaccine. We used LAIV-virus shedding as a surrogate of influenza infection. Influenza-specific humoral and mucosal antibody levels were significantly higher in nonshedders than in shedders. CONCLUSIONS: LAIV and TIV generated homotypic and heterosubtypic humoral and mucosal antibody responses in HIV-infected children. High titers of humoral or mucosal antibodies correlated with protection against viral shedding. PMID- 20581693 TI - The effect of neuromuscular electrical stimulation on congenital talipes equinovarus following correction with the Ponseti method: a pilot study. AB - The Ponseti method for clubfoot treatment offers satisfactory initial correction, but success correlates with abduction brace compliance, which is variable. Electrical stimulation as a dynamic intervention to prevent relapses was investigated. Data were compared to a control group. There was a significant improvement in ankle range of motion only in the study group after short-term intervention, and a trend toward greater increase in calf circumference in this group. Parental perception was positive with no compliance issues. This study suggests stimulation is feasible with potential to increase ankle range of motion and facilitate muscle activity. It could be an important adjunct in preventing relapses, however, further studies with larger groups and longer intervention and follow-up duration are necessary. PMID- 20581694 TI - Ponseti's manipulation in neglected clubfoot in children more than 7 years of age: a prospective evaluation of 25 feet with long-term follow-up. AB - We wanted to evaluate the efficacy of Ponseti's technique in neglected clubfoot in children more than 7 years of age. The results of Ponseti's method were evaluated in 21 children (25 feet) with neglected club feet. Patients were evaluated using the Dimeglio scoring system. All patients underwent percutaneous tenotomy of the Achilles tendon. The mean age at the time of treatment was 8.9 years. The mean follow-up period was 4.7 years. The average Dimeglio score at the start of the treatment was 14.2 compared with an average score of 0.95 at the end of the treatment at 1-year follow-up. Eighteen feet (85.7%) had full correction. Recurrence was seen in six feet (24%). At 4-year follow-up, the average Dimeglio score for 19 feet was 0.18. We recommend that Ponseti's method should be the preferred initial treatment modality for neglected clubfeet. PMID- 20581695 TI - Effects of saddle height on economy and anaerobic power in well-trained cyclists. AB - In cycling, saddle height adjustment is critical for optimal performance and injury prevention. A 25-35 degrees knee angle is recommended for injury prevention, whereas 109% of inseam, measured from floor to ischium, is recommended for optimal performance. Previous research has demonstrated that these 2 methods produce significantly different saddle heights and may influence cycling performance. This study compared performance between these 2 methods for determining saddle height. Subjects consisted of 11 well-trained (VO2max = 61.55 +/- 4.72 ml.kg.min) male cyclists. Subjects completed a total of 8 performance trials consisting of a graded maximal protocol, three 15-minute economy trials, and 4 anaerobic power trials. Dependent measures for economy (VO2, heart rate, and rating of perceived exertion) and anaerobic power (peak power and mean power) were compared using repeated measures analysis of variance (alpha = 0.05). VO2 was significantly lower (reflecting greater economy) at a 25 degrees knee angle (44.77 +/- 6.40 ml.kg.min) in comparison to a 35 degrees knee angle (45.22 +/- 6.79 ml.kg.min) and 109% of inseam (45.98 +/- 5.33 ml.kg.min). Peak power at a 25 degrees knee angle (1,041.55 +/- 168.72 W) was significantly higher in relation to 109% of inseam (1,002.05 +/- 147.65 W). Mean power at a 25 degrees knee angle (672.37 +/- 90.21 W) was significantly higher in relation to a 35 degrees knee angle (654.71 +/- 80.67 W). Mean power was significantly higher at 109% of inseam (662.86 +/- 79.72 W) in relation to a 35 degrees knee angle (654.71 +/- 80.67 W). Use of 109% of inseam fell outside the recommended 25-35 degrees range 73% of the time. Use of 25 degrees knee angle appears to provide optimal performance while keeping knee angle within the recommended range for injury prevention. PMID- 20581696 TI - Medial and lateral gastrocnemius activation differences during heel-raise exercise with three different foot positions. AB - Despite little objective support, heel-raise exercises are commonly performed using varying foot positions in an attempt to alter medial (MG) and lateral (LG) gastrocnemius involvement. This investigation compared MG and LG activation during the concentric phase (CP) and eccentric phase (EP) of the heel-raise exercise using neutral (NE), internally rotated (IR), and externally rotated (ER) foot positions. Twenty healthy subjects (10 men, 10 women; age = 23.7 +/- 3.1 years) with resistance training experience performed free-weight (130-135% body mass) heel-raise exercise on a 3.81-cm block. Surface electromyography activity was recorded during 10 repetitions of each foot position. Electromyography activity from 5 successful repetitions was normalized to maximum voluntary isometric contraction, ensemble averaged within phase (CP, EP), and the mean amplitude determined. Significant (p < 0.05) muscle-by-foot position interactions were revealed for both phases. The ER position prompted significantly greater MG activation than LG during both phases, whereas the IR position elicited significantly greater LG activation than MG. These data support the notion that altering foot position during heel-raise exercise will prompt varying degrees of MG and LG activation. Although this study cannot predict whether muscle activation differences between foot positions will translate into greater training adaptations, it does provide some initial objective evidence upon which practitioners can base the selection of gastrocnemius exercises. PMID- 20581697 TI - Effect of core stability training on throwing velocity in female handball players. AB - The purpose was to study the effect of a sling exercise training (SET)-based core stability program on maximal throwing velocity among female handball players. Twenty-four female high-school handball players (16.6 +/- 0.3 years, 63 +/- 6 kg, and 169 +/- 7 cm) participated and were initially divided into a SET training group (n = 14) and a control group (CON, n = 10). Both groups performed their regular handball training for 6 weeks. In addition, twice a week, the SET group performed a progressive core stability-training program consisting of 6 unstable closed kinetic chain exercises. Maximal throwing velocity was measured before and after the training period using photocells. Maximal throwing velocity significantly increased 4.9% from 17.9 +/- 0.5 to 18.8 +/- 0.4 m.s in the SET group after the training period (p < 0.01), but was unchanged in the control group (17.1 +/- 0.4 vs. 16.9 +/- 0.4 m.s). These results suggest that core stability training using unstable, closed kinetic chain movements can significantly improve maximal throwing velocity. A stronger and more stable lumbopelvic-hip complex may contribute to higher rotational velocity in multisegmental movements. Strength coaches can incorporate exercises exposing the joints for destabilization force during training in closed kinetic chain exercises. This may encourage an effective neuromuscular pattern and increase force production and can improve a highly specific performance task such as throwing. PMID- 20581698 TI - Three days of static stretching within a warm-up does not affect repeated-sprint ability in youth soccer players. AB - This study aimed to examine the repeated-sprint ability (RSA) in soccer players after 3 days of static stretching. Twenty soccer players (age: 16.8 +/- 0.4 years) participated in 2 series of experiments with within-subject repeated measure design (control series [CON]: 13-minute aerobic warm-up; and static stretching series [SS]: 10-minute aerobic warm-up and 3-minute static stretching). Each series consisted of 5 days, and RSA (9 * 30 m separated by 25 second passive recovery) was tested on days 1 and 5. Static stretching was performed for 3 consecutive days from days 2-4, before and after intermittent aerobic endurance exercise on each day. The same warm-up protocol was used before and after all RSA tests and exercises within 1 series. No significant difference between CON and SS was observed (p > 0.05) in RSA for overall (all sprints), early phase (first to third sprints), middle phase (fourth to sixth sprints), and final phase (seventh to ninth sprints). Short-term static stretching had trivial effects (Cohen's d < 0.35) on overall and split RSA phases (early, middle, and final). The present study showed that performing static stretching for 3 consecutive days and before repeated-sprint test did not negatively affect RSA. However, it is premature to recommend that static stretching could be included in in-season daily warm-up routine because some movements such as jump and single sprint were more sensitive to static stretching. PMID- 20581699 TI - Oxidative stress biomarker responses to an acute session of hypertrophy resistance traditional interval training and circuit training. AB - We have studied circuit resistance schemes with high loads as a time-effective alternative to hypertrophy-traditional resistance training. However, the oxidative stress biomarker responses to high-load circuit training are unknown. The aim of the present study was to compare oxidative stress biomarker response with an acute session of hypertrophy-resistance circuit training and traditional interval training. A week after the 1 repetition maximum (1RM) test, 11 healthy and well-trained male participants completed hypertrophy-resistance acute sessions of traditional interval training (3 * 10 repetitions at 75% of the 1RM, with 90-second passive rest) and circuit training (3 * 10 repetitions at 75% of the 1RM, in alternating performance of 2 exercises with different muscle groups) in a randomized and cross-over design. Venous blood samples were collected before (pre) and 10 minutes after (post) the resistance training sessions for oxidative stress biomarker assays. As expected, the time used to complete the circuit training (20.2 +/- 1.6) was half of that needed to complete the traditional interval training (40.3 +/- 1.8). Significant increases (p < 0.05) in thiobarbituric acid reactive substances (40%), creatine kinase (CK) (67%), glutathione (14%), and uric acid (25%) were detected posttraditional interval training session in relation to pre. In relation to circuit training, a significant increase in CK (33%) activity postsession in relation to pre was observed. Statistical analysis did not reveal any other change in the oxidative stress biomarker after circuit training. In conclusion, circuit resistance hypertrophy training scheme proposed in the current study promoted lower oxidative stress biomarkers and antioxidant modulations compared with resistance traditional interval training. PMID- 20581700 TI - VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L arginine supplementation. AB - The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean +/- SD, age: 36.3 +/- 7.9 years; height: 182.4 +/- 4.6 cm; and body mass: 79.5 +/- 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W.min) before and after 28 days of supplementation with L-arginine (ARG; 2 * 6 g.d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 +/- 7.1 ml.kg.min; ARG, 63.5 +/- 7.3 ml.kg.min) to postsupplement VO2max (PL, 58.9 +/- 6.0 ml.kg.min; ARG, 63.2 +/- 7.2 ml.kg.min). Also, no effect was seen from initial VT (PL, 75.7 +/- 4.6% VO2max; ARG, 76.0 +/- 5.3% VO2max) to postsupplement VT (PL, 74.3 +/- 8.1% VO2max; ARG, 74.2 +/- 6.4% VO2max). These results indicate that L arginine does not impact VO2max or VT in trained male cyclists. PMID- 20581701 TI - Longitudinal changes in bone mineral density in male master cyclists and nonathletes. AB - This study tracked changes in bone mineral density (BMD) over a 7-year period in competitive male master cyclists (n = 19) and nonathletes (n = 18). Participants completed health/exercise history and food frequency (for calcium intake) questionnaires and underwent BMD testing by dual-energy X-ray absorptiometry. At initial and 7-year assessments, there was a consistent pattern of lower BMD in cyclists compared to nonathletes at all bone sites measured. Repeated measures analysis of covariance adjusted for changes in body mass index, lean mass, calcium intake, and exercise habits indicated a significant interaction at the total body site, indicating greater BMD decline in cyclists than nonathletes (p < 0.05). Among all study participants, those who reported participating in weight training or impact exercise since the baseline assessment lost significantly less BMD at the spine and femoral neck compared to participants who reported no weight training/impact exercise since baseline (p < 0.05). A significantly greater percentage of cyclists than nonathletes met the International Society of Clinical Densitometry criteria for osteopenia or osteoporosis at baseline (84.2% vs. 50.0%) and at follow-up (89.5% vs. 61.1%, p < 0.05). Further, 6 of the 19 (31.6%) cyclists who had osteopenia at baseline became osteoporotic, compared to 1 (5.6%) of the nonathletes. The high percentage of male master cyclists with low BMD, combined with a high risk for fracture from falls associated with competitive cycling, warrant attention among this population. Coaches and health professionals interacting with cyclists need to promote alternative exercise such as weight training, plyometrics, or other high impact activity as a complement to cycle training to help minimize bone loss in this population. PMID- 20581702 TI - The influence of variable range of motion training on neuromuscular performance and control of external loads. AB - Resistance training programs that emphasize high force production in different regions of the range of motion (ROM) may provide performance benefits. This study examined whether variable ROM (VROM) training, which consists of partial ROM training with countermovements performed in a different phase of the ROM for each set, results in improved functional performance. Twenty-two athletes (age 22.7 +/ 2.4 years, height 1.81 +/- 0.07 m, and body mass 94.6 +/- 14.5 kg) with extensive resistance training backgrounds performed either a VROM or full ROM control (CON) 5-week, concentric work-matched training program. The participants were assigned to a group based on stratified randomization incorporating their strength levels and performance gains in preceding training microcycles. Testing consisted of assessing the force-ROM relationship during isokinetic and isometric bench press and ballistic bench throws, with normalized electromyography amplitude assessed during the isometric tests. Repeated-measure analyses of variance revealed that the VROM intervention significantly (p < 0.05) increased both full ROM bench throw displacement (+15.5%) and half ROM bench throw peak force (+15.7%), in addition to isokinetic peak force in the terminal ROM (13.5% increase). No significant differences were observed in the CON group or between groups for any other outcome measures. Analysis of the force-ROM relationship revealed that that the VROM intervention enhanced performance at shorter muscle lengths. These findings suggest that VROM training improves terminal and midrange performance gains, resulting in the athlete possessing an improved ability to control external loading and produce dynamic force. PMID- 20581703 TI - A comparison of traditional and weekly undulating periodized strength training programs with total volume and intensity equated. AB - The purpose of this study was to compare the training adaptations attained during 12 weeks of traditional (TD) and weekly undulating (WUD) periodized strength training. Forty-two recreationally active men (age = 22 +/- 2.3 years) were randomly assigned to 1 of 3 groups: control (C) (n = 14), TD (n = 14), or WUD (n = 14). Ten-repetition maximum (10RM) laboratory testing was carried out for the free weight back squat and the free weight flat bench press at baseline, week 8, and week 12. The subjects trained 3 d.wk (approximately 135 min.wk) from weeks 1 to 2 and 4 d.wk from week 3 to week 12 (approximately 180 min.wk). The TD and WUD groups trained using a periodized strength program with all program variables controlled (e.g., volume and intensity). The independent variable was the manipulation of intensity. The TD group used a linear increase in intensity, whereas the WUD group had a varied intensity. The results showed that both the TD and WUD groups made significant (p <= 0.05) increases in strength at weeks 8 and 12, but by week 12, the TD group was significantly (p <= 0.05) stronger than the WUD group. These results indicate that TD periodization with a linear increase in intensity was more effective at eliciting strength gains than WUD periodization with a varied intensity. The differences in strength gains between the TD and WUD groups may be related to extended periods of muscle soreness and fatigue that were present in the WUD group but not in the TD group. Thus, during long-term training, individuals may benefit more from TD periodized programs because there may be less muscle soreness and fatigue to disrupt practice and training. PMID- 20581704 TI - A practical approach to monitoring recovery: development of a perceived recovery status scale. AB - The aim of this study was to develop and test the practical utility of a perceived recovery status (PRS) scale. Sixteen volunteers (8 men, 8 women) performed 4 bouts of high-intensity intermittent sprint exercise. After completion of the baseline trial, in a repeated-measures design, subjects were given variable counterbalanced recovery periods of 24, 48, and 72 hours whereupon they repeated an identical intermittent exercise protocol. After a warm-up period, but before beginning each subsequent bout of intermittent sprinting, each individual provided their perceived level of recovery with a newly developed PRS scale. Similar to perceived exertion during exercise, PRS was based on subjective feelings. The utility of the PRS scale was assessed by measuring the level of agreement of an individual's perceived recovery relative to their performance during the exercise bout. Perceived recovery status and change (both positive and negative) in sprint performance during multiple bouts of repeated sprint exercise were moderately negative correlated (r = -0.63). Additionally, subjects were able to accurately assess level of recovery using the PRS scale indicated by correspondence with negative and positive changes in total sprint time relative to their previous session. The ability to detect changes in performance using a noninvasive psychobiological tool to identify differences in performance was independent of other psychological and physiological markers measured during testing, because there were no differences (p > 0.05) among ratings of perceived exertion (RPE), heart rate, blood lactate concentration, or session RPE values among any of the performance trials. Although further study is needed, current results indicate a subjective approach may be an effective means for assessing recovery from day to day, at least under similar conditions. PMID- 20581705 TI - Precision in the prediction of middle distance-running performances using either a nomogram or the modeling of the distance-time relationship. AB - The purpose was to determine the levels of precision in the prediction of middle distance performances in running using the modeling of the distance-time relationship and a nomogram. Official French running rankings for the men's 3,000; 5,000; and 10,000 m were scrutinized from 1996 to 2007. Only runners who competed over the 3 distances within the same year were included (n = 100). The distance-time relationship was modeled using a linear 2-parameter model from the plot of 2 performances to predict a third one. The nomogram of Mercier was also used to predict 1 performance from the use of the other 2. Actual and predicted performances were significantly different, except for the 5,000- and 10,000-m performances predicted from the nomogram (p > 0.05). Effect sizes (ESs) were lower when the performance was predicted by the nomogram (-0.25 < ES < 0.05) compared with the linear 2-parameter model (-0.99 < ES < 0.47). The predicted performances were significantly correlated to the actual performances (r > 0.46; p < 0.01). The bias +/- limits of agreement for the 3,000-; 5,000-; and 10,000-m performances were 1.0 +/- 12.8, -0.1 +/- 6.9, and 0.1 +/- 20.8% and 3.7 +/- 15.5, -1.4 +/- 6.2, and 2.5 +/- 10.6% for prediction from the nomogram and distance time relationship, respectively. Although the modeling of the distance-time relationship does not enable middle-running performances to be accurately predicted, the precision in the predictions from the nomogram suggests that the nomogram may be used to prescribe adapted training intensities and determine the optimal strategy during the race. PMID- 20581706 TI - The acute effect of whole-body low-frequency vibration on countermovement vertical jump performance in college-aged men. AB - The purpose of this study was to examine the acute effects of whole-body vibration on jump performance. A total of 21 college-aged men, 18-30 years, recreationally resistance trained, were exposed to a total of 4 different acute whole-body low-frequency vibration (WBLFV) protocols (conditions 1-4), performing 2 protocols per testing session in random order. Exposures were all performed using high-amplitude (peak-peak 4-6 mm) and either 30 or 50 Hz for 30 continuous seconds, or 3 exposures of 10 seconds with 1 minute between exposures. Three countermovement vertical jumps (CMVJs) were performed before vibration (testing phase 1 or Tp1 and J1 the highest of 3 attempts) and at 3 separate time points postvibration (Tp2-4). Jump height (cm), peak power (Pmax), peak power per kilogram of body mass (Pmax kg), mean power (Pav), and mean velocity (Vav) were recorded. Repeated measures analysis of variance and analysis of covariance revealed no significant condition (C) or jump (J) differences for CMVJ height (cm) (p > 0.05). Analysis of percent change (Delta%) for CMVJ height (cm) revealed a significant Condition * Jump interaction, C4, J3 > C1, J3 (p = 0.009, mean diff 4.12%). Analysis of Pmax and Pmax kg revealed no significant Condition, Jump, or Condition * Jump interaction for the raw data or percent change (p > 0.05). Analysis of Pav (W) revealed significant differences for Condition (p = 0.031) but not for Jump (p = 0.226). There was a strong trend toward significance for Condition * Jump interaction (p = 0.059). C4 > C3 (p = 0.043, mean diff 23.78 W) and C1 (p = 0.038, mean diff 32.03 W). Analysis of Vav (m.s) revealed no significant main effects for Condition or Jump (p > 0.05) but found a significant Condition * Jump interaction (p = 0.007). C4, J6 > C2, J6 (p = 0.014, mean diff 0.05 m.s), and C3, J6 (p = 0.020, 0.05 m.s). WBLFV applied intermittently using 50 Hz appears to be more effective than other protocols using 30 and 50 Hz in facilitating select measures of CMVJ performance over a 17-minute time period post-WBLFV exposure. Practical manipulation of such a WBLFV "dose" may be beneficial to strength and conditioning practitioners wanting to acutely facilitate CMVJ and slow stretch shortening cycle performance while minimizing exposure time. PMID- 20581707 TI - Apelin expression in human non-small cell lung cancer: role in angiogenesis and prognosis. AB - INTRODUCTION: The recently discovered bioactive peptide, apelin, has been demonstrated to stimulate angiogenesis in various experimental systems. However, its clinical significance and role in tumor vascularization have not yet been investigated in a human malignancy. Therefore, our aim was to study whether apelin expression is associated with angiogenesis and/or tumor growth/behavior in human non-small cell lung cancer (NSCLC). METHODS: A total of 94 patients with stage I-IIIA NSCLC and complete follow-up information were included. Apelin expression in human NSCLC samples and cell lines was measured by quantitative reverse-transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Effects of exogenous apelin and apelin transfection were studied on NSCLC cell lines in vitro. In vivo growth of tumors expressing apelin or control vectors were also assessed. Morphometric variables of human and mouse tumor capillaries were determined by anti-CD31 labeling. RESULTS: Apelin was expressed in all of the six investigated NSCLC cell lines both at the mRNA and protein levels. Although apelin overexpression or apelin treatments did not increase NSCLC cell proliferation in vitro, increasing apelin levels by gene transfer to NSCLC cells significantly stimulated tumor growth and microvessel densities and perimeters in vivo. Apelin mRNA levels were significantly increased in human NSCLC samples compared with normal lung tissue, and high apelin protein levels were associated with elevated microvessel densities and poor overall survival. CONCLUSIONS: This study reveals apelin as a novel angiogenic factor in human NSCLC. Moreover, it also provides the first evidence for a direct association of apelin expression with clinical outcome in a human cancer. PMID- 20581708 TI - Cost-effectiveness of pemetrexed as first-line maintenance therapy for advanced nonsquamous non-small cell lung cancer. AB - INTRODUCTION: The primary objective was to estimate the cost-effectiveness of maintenance therapy with pemetrexed (Pem) compared with observation, each with best supportive care, in patients with advanced non-small cell lung cancer (NSCLC) who have completed, without progression, at least four cycles of first line platinum chemotherapy, particularly in those with nonsquamous cell histology. Secondary comparisons included Pem with erlotinib (Erl) or Pem with bevacizumab (Bev). METHODS: A semi-Markov model was developed to compare the 3 year impact of Pem with three other alternatives for maintenance therapy from a United States payer perspective. Data from randomized controlled clinical trials provided clinical inputs. Medicare reimbursement rates were used to determine drug costs. A retrospective claims database analysis was used to obtain estimates of other direct NSCLC-related costs. RESULTS: In the prespecified subset of patients with nonsquamous cell histology only, the incremental cost per life-year gained was $122,371 for Pem to observation and $150,260 for Pem to Erl, and Bev was dominated by Pem. In all patients with advanced NSCLC regardless of histologic subtype, using Pem as maintenance therapy led to an incremental cost per life-year gained of $205,597 compared with observation and $312,341 compared with Erl. CONCLUSIONS: Compared with observation and other agents used and/or reimbursed for maintenance therapy in advanced NSCLC, Pem may be considered cost effective, particularly in patients with nonsquamous cell histology. This analysis is the first to evaluate the cost-effectiveness of maintenance therapy in advanced NSCLC and emphasizes the importance of histology in identifying the appropriate patient for Pem maintenance therapy. PMID- 20581709 TI - A pragmatic approach to the diagnosis of nodal micrometastases in early stage non small cell lung cancer. AB - INTRODUCTION: This study was designed to develop a both sensitive and efficient algorithm for detection of lymph node micrometastases and to determine its prognostic impact in patients with early stage non-small cell lung cancer (NSCLC). METHODS: One hundred seventy patients with NSCLC p stage I and II were included in this study, of which n = 5299 lymph nodes were obtained and submitted to histopathologic analysis. From each patient, a median number of 31 lymph nodes was received (N-1 position: median n = 16; N-2 position: median n = 15). Immunohistochemistry was performed to detect micrometastases unobvious by conventional microscopy using antibodies against cytokeratins (CK) (pan-CK: KL-1, CK 5/6, CK 7) and the epithelial marker Ber-EP4. RESULTS: In 82 patients (48.2%), micrometastases were revealed in immunohistochemistry staining. KL-1 detected micrometastases in 201 (99.5%) of 202 positive lymph nodes. Subsequently, this resulted in an upstaging in 39 patients (20.5%). Detection of micrometastases in otherwise tumor-free N2-lymph nodes had a significant prognostic impact (mean disease-free survival 21.4 versus 45.3 months, p = 0.022), affecting 4.7% of patients. Survival differences between patients who were upstaged into stage II (N0>N1) and those remaining in stage I were not statistically significant (p = 0.537). CONCLUSION: Extended workup of N2-lymph nodes using one broad-spectrum keratin marker in otherwise N2-negative lymph nodes may represent a both efficient and sensitive approach to the identification of micrometastases in dissected lymph nodes of patients with early stage NSCLC. PMID- 20581710 TI - The finding of premalignant lesions is not associated with smoking cessation in chemoprevention study volunteers. AB - BACKGROUND AND STUDY AIMS: Screening programs for lung cancer may lead to a heightened awareness of the risks of smoking and enhance quitting. The aim of this study was to evaluate whether the participation on a chemoprevention study for premalignant lesions could influence smoking cessation. METHODS: Two hundred one volunteers, current (n = 188) and former smokers (n = 13) with more than 20 pack years had been screened for the chemoprevention study. One hundred forty-six of the current smokers at time of chemoprevention study screening have been retrospectively interviewed about their smoking behavior > or =1 year after their first contact for the chemoprevention study. Structured questionnaires were used, and interviews were held by telephone. The quitters at the time of these first interviews were contacted again 4 years after the initial interview about their current smoking behavior. RESULTS: Of the 146 smoking volunteers, 83 were diagnosed with premalignant lesions of the bronchial mucosa and participated in the chemoprevention study, and 63 had no premalignant lesions and were not included in that study.The majority of participants were men: 87 (60%). The mean age of the participants was 52 +/- 9 years, and the mean age at which volunteers started smoking was 15 +/- 3. Mean number of pack years was 47 +/- 27. Ten volunteers in the group without premalignant lesions and 19 in the group with premalignant lesions had quit smoking at time of the first interview. The smoking cessation rate of the total study group was 20%.Univariate logistic regression analysis demonstrated that smoking cessation was only significantly associated with male gender. No significant associations were found between smoking cessation and the finding of premalignant lesions, sex, age, level of addiction, educational level, marital condition, history of cancer/pulmonary diseases, age at start smoking, previous attempts to quit smoking, and motivation to quit smoking.Within the group of subjects who had quit smoking at the time of the first interview, 15 of 29 persons who had stopped smoking at the time of the first interview have reported that participation in the bronchoscopy screening and/or the trial has been of major influence on their decision to stop smoking. CONCLUSIONS: A smoking cessation rate of 20% has been found among volunteers for a chemopreventive trial investigating smoking-related premalignant lesions after almost 2 years after initial contact has been found. Volunteers experienced screening and trial participation as having influenced their smoking cessation. Smoking cessation was significantly associated with male gender, whereas the finding of premalignant lesions by bronchoscopy was not. PMID- 20581711 TI - Effects of strength training on muscle fatigue mapping from surface EMG and blood metabolites. AB - PURPOSE: this study examined the effects of heavy resistance training on the relationships between power loss and surface EMG (sEMG) indices and blood metabolite concentrations on dynamic exercise-induced fatigue with the same relative load as in pretraining. METHODS: twelve trained subjects performed five sets consisting of 10 repetitions in the leg press, with 2 min of rest between sets before and after a strength training period. sEMG variables (the mean average voltage, the median spectral frequency, and the Dimitrov spectral index of muscle fatigue) from vastus medialis and lateralis muscles and metabolic responses (i.e., blood lactate, uric acid, and ammonia concentrations) were measured. RESULTS: the peak power loss after the posttraining protocol was greater (61%) than the decline observed in the pretraining protocol (46%). Similar sEMG changes were found for both protocols, whereas higher metabolic demand was observed during the posttraining exercise. The linear models on the basis of the relations found between power loss and changes in sEMG variables were significantly different between pretraining and posttraining, whereas the linear models on the basis of the relations between power loss and changes in blood metabolite concentrations were similar. CONCLUSIONS: linear models that use blood metabolites to map acute exercise-induced peak power changes were more accurate in detecting these changes before and after a short-term training period, whereas an attempt to track peak power loss using sEMG variables may fail after a strength training period. PMID- 20581712 TI - Effects of camber on the ergonomics of propulsion in wheelchair athletes. AB - PURPOSE: to examine the effects of rear-wheel camber on the physiological and biomechanical responses during manual wheelchair propulsion in highly trained wheelchair athletes. METHODS: participants (N = 14) pushed on a motorized treadmill (2.2 m.s, 0.7% gradient) in four standardized camber conditions (15 degrees , 18 degrees , 20 degrees , and 24 degrees ). Standardization was achieved by controlling seat height, the distance between top dead center of the main wheels and "toe-in toe-out" across all camber settings. Power output (PO) and cardiorespiratory measures were collected for each camber setting. Three dimensional upper body joint kinematics were also analyzed via two high-speed video cameras (100 Hz). One-way ANOVA with repeated measures was applied to all data with statistical significance accepted when P < 0.05. RESULTS: a significantly higher PO was observed for 24 degrees camber (24.3 W) in relation to 15 degrees (20.3 W) and 18 degrees (21.3 W), and also for 20 degrees (23.3 W) in relation to 15 degrees . This resulted in an improvement in mechanical efficiency (ME) for both 24 degrees (6.8%) and 20 degrees (6.7%) compared with 15 degrees (5.9%). However, significantly higher oxygen uptake (reduced economy) and HR responses were observed for 24 degrees (1.04 L.min; 105 bpm) compared with 15 degrees (0.98 L.min; 102 bpm) and 18 degrees (0.97 L.min; 102 bpm). Also, significantly greater ranges of motion were established for shoulder flexion and elbow extension during the push phase for 24 degrees and were likely to have contributed toward the increased oxygen cost in this setting. CONCLUSIONS: this study revealed that 20 degrees and 24 degrees camber improved the ME of wheelchair propulsion in highly trained wheelchair athletes, yet these increased external power requirements and reduced the economy. PMID- 20581713 TI - Physical activity, stress, and self-reported upper respiratory tract infection. AB - PURPOSE: upper respiratory tract infection (URTI) is the most common reason for seeking primary care in many countries. Still, little is known about potential strategies to reduce susceptibility. We investigated the relationships between physical activity level, perceived stress, and incidence of self-reported URTI. METHODS: we conducted a population-based prospective cohort study of 1509 Swedish men and women aged 20-60 yr with a follow-up period of 4 months. We used a Web based questionnaire to assess disease status and lifestyle factors at the start of the study. We assessed physical activity and inactivity as total MET-hours (MET task) per day and perceived stress by the 14-item Perceived Stress Scale. Participants were contacted every 3 wk via e-mail to assess incidence of URTI. They reported a total of 1181 occurrences of URTI. We used Poisson regression models to control for age, sex, and other potential confounding factors. RESULTS: we found that high levels of physical activity (>= 55 MET.h.d) were associated with an 18% reduced risk (incidence rate ratio (IRR) = 0.82, 95% confidence interval (CI) = 0.69-0.98) of self-reporting URTI compared with low levels of physical activity (<45 MET.h.d). This association was stronger among those reporting high levels of stress (IRR = 0.58, 95% CI = 0.43-0.78), especially among men (IRR = 0.37, 95% CI = 0.24-0.59), but absent in the group with low levels of stress. CONCLUSIONS: we found that high physical activity was associated with a lower risk of contracting URTI for both men and women. In addition, we found that highly stressed people, particularly men, appear to benefit more from physical activity than those with lower stress levels. PMID- 20581714 TI - Better with a buddy: influence of best friends on children's physical activity. AB - PURPOSE: the purpose of this study was to examine the extent to which the physical activity modeling and physical activity actions of best friends are associated with the physical activity of 10- to 11-yr-old children. METHODS: data were collected from 986 children of whom 472 provided complete physical activity and best friend data. Participants identified their "best friend" within the school and answered how often they took part in physical activity with the friend and if the friend had encouraged them to be active. Physical activity was assessed via accelerometer for all children and friends. Mean minutes of moderate to-vigorous physical activity per day (MVPA) and mean accelerometer counts per minute (CPM) were obtained for all children and best friends. Regression models were run separately for boys and girls and used to examine associations between child and best friend physical activity. RESULTS: for girls, mean MVPA was associated with frequency of activity of the best friend (P <= 0.02 for all categories) and engaging in physical activity at home or in the neighborhood (t = 2.27, P = 0.030), with similar patterns for mean CPM. Boys' mean MVPA was associated with their best friend's mean MVPA (t = 3.68, P = 0.001) and being active at home or in the local neighborhood (t = 2.52, P = 0.017). CONCLUSIONS: boys who have active friends spend more minutes in MVPA. Girls who frequently take part in physical activity with their best friend obtain higher levels of physical activity. Boys and girls who take part in physical activity with their best friend at home or in the neighborhood where they live engage in higher levels of physical activity. PMID- 20581715 TI - Spectral analysis of point processes: motor unit activity and heart rate analysis. AB - PURPOSE: point process data, which are data consisting of event times, arise often in studies of exercise physiology. The frequency content, that is, power spectrum, of point process data reflects physiological control processes. Several methods have been proposed for estimating the power spectrum of point process data. The purpose of this study was to compare the different methods for power spectrum analysis of point process data, using motor unit activity and HR as examples. METHODS: the times of motor unit firing during periodic tasks and of heart beats during natural and paced breathing were determined from EMG and from ECG. The frequency content was determined using the point process Fourier transform, the nonparametric estimate of the power spectrum, and a parametric (model-based) spectral estimate. In the case of the latter two approaches, we also compared the use of the interevent interval signal and the rate signal. The power at the task frequency was computed from the motor unit data. The ratio of power in low-frequency (LF) and high-frequency (HF) bands, used to assess autonomic status, was computed from HR spectra. Simulation data were also generated and analyzed. RESULTS: the different methods found slightly but significantly different motor unit power at the task frequency. The LF/HF ratios derived from the nonparametric and the parametric spectra were highly correlated with each other. LF/HF ratios derived from point process spectra were not correlated with the corresponding ratios derived from nonparametric or parametric spectra. CONCLUSIONS: the three methods of power spectrum estimation yield similar but not identical results. Caution must be used when assessing the LF/HF ratio from point process power spectra. PMID- 20581716 TI - Validation of accelerometer wear and nonwear time classification algorithm. AB - INTRODUCTION: the use of movement monitors (accelerometers) for measuring physical activity (PA) in intervention and population-based studies is becoming a standard methodology for the objective measurement of sedentary and active behaviors and for the validation of subjective PA self-reports. A vital step in PA measurement is the classification of daily time into accelerometer wear and nonwear intervals using its recordings (counts) and an accelerometer-specific algorithm. PURPOSE: the purpose of this study was to validate and improve a commonly used algorithm for classifying accelerometer wear and nonwear time intervals using objective movement data obtained in the whole-room indirect calorimeter. METHODS: we conducted a validation study of a wear or nonwear automatic algorithm using data obtained from 49 adults and 76 youth wearing accelerometers during a strictly monitored 24-h stay in a room calorimeter. The accelerometer wear and nonwear time classified by the algorithm was compared with actual wearing time. Potential improvements to the algorithm were examined using the minimum classification error as an optimization target. RESULTS: the recommended elements in the new algorithm are as follows: 1) zero-count threshold during a nonwear time interval, 2) 90-min time window for consecutive zero or nonzero counts, and 3) allowance of 2-min interval of nonzero counts with the upstream or downstream 30-min consecutive zero-count window for detection of artifactual movements. Compared with the true wearing status, improvements to the algorithm decreased nonwear time misclassification during the waking and the 24-h periods (all P values < 0.001). CONCLUSIONS: the accelerometer wear or nonwear time algorithm improvements may lead to more accurate estimation of time spent in sedentary and active behaviors. PMID- 20581718 TI - Knee joint laxity and its cyclic variation influence tibiofemoral motion during weight acceptance. AB - PURPOSE: to better understand how sex differences in anterior knee laxity (AKL) affect knee joint biomechanics, we examined the consequence of greater absolute baseline (males and females) and cyclic increases in AKL during the menstrual cycle (females) on anterior tibial translation (ATT) as the knee transitioned from non-weight-bearing to weight-bearing conditions, while also controlling for genu recurvatum (GR). METHODS: males and females (71 females and 48 males, aged 18-30 yr) were measured for AKL and GR and underwent measurement of ATT. Women were tested on the days of their cycle when AKL was at its minimum (T1) and maximum (T2); males were matched in time to a female with similar AKL. Linear regressions examined relationships between absolute baseline (AKLT1, GRT1) and cyclic changes (Delta = T2 - T1; AKLDelta, GRDelta) (females only) in knee laxity with ATT as measured at T1 and T2 and Delta (T2 - T1) (females only). RESULTS: AKL and GR increased in females, but not in males, from T1 to T2. Greater AKLT1 and GRT1 predicted greater ATTT1 and ATTT2 in males (R = 21.0, P < 0.007). The combination of greater AKLT1, AKLDelta, and less GRDelta predicted greater ATTT1 and ATTT2 in females (R = 12.5-13.1, P < 0.05), with AKLDelta being a stronger predictor (coefficient, P value) of ATTT2 (0.864, P = 0.027) compared with ATTT1 (0.333, P = 0.370). AKLDelta was the sole predictor of ATTDelta (R = 0.104 and 0.740, P = 0.042). CONCLUSIONS: greater absolute baseline and cyclic increases in AKL were consistently associated with greater ATT produced by transition of the knee from non-weight-bearing to weight-bearing. Because the anterior cruciate ligament is the primary restraint to ATT, these findings provide insight into the possible mechanisms by which greater AKL may be associated with at-risk knee biomechanics during the weight acceptance phase of dynamic tasks. PMID- 20581717 TI - Cardiorespiratory fitness, adiposity, and serum 25-dihydroxyvitamin d levels in men. AB - PURPOSE: we examined the cross-sectional associations between cardiorespiratory fitness (CRF) level, different measures of adiposity, and serum 25 dihydroxyvitamin D levels (SVD) in men. METHODS: a total of 2317 men completed a baseline health examination between 2005 and 2009. Clinical measures included body mass index (BMI), waist circumference (WC), waist-to-hip ratio (W:Hip), percent body fat, CRF quantified as duration of a maximal treadmill exercise test, and measurement of SVD. Participants were classified by CRF as "unfit" (lowest 20%) and "fit" (remaining 80%) based on age as well as by clinical cut points for BMI, WC, W:Hip, and percent body fat and by categories of SVD. We examined trends of CRF and adiposity exposures across SVD categories. We also calculated odds ratios (OR) of abnormal SVD across levels of adiposity exposures before and after adjusting for CRF as well as OR of abnormal SVD across levels of CRF before and after adjusting for each adiposity exposure. RESULTS: we observed a significant positive trend for CRF across incremental SVD categories (P < 0.001), with the highest mean age-adjusted CRF levels (11.9 +/- 1.9 METs) in the highest SVD category. When compared with normal-weight men, OR for abnormal SVD was significantly higher for overweight men within each adiposity exposure (P < 0.05). Joint associations among CRF, adiposity, and SVD revealed significantly lower SVD in unfit than in fit men within each stratum of each adiposity exposure. CONCLUSIONS: SVD levels are positively associated with CRF and are negatively associated with different measures of adiposity in men. Higher CRF attenuates the relationship between adiposity level and SVD. Because the observed associations are cross-sectional, future prospective studies are warranted. PMID- 20581719 TI - Effects of aerobic training on airway inflammation in asthmatic patients. AB - PURPOSE: there is evidence suggesting that physical activity has anti inflammatory effects in many chronic diseases; however, the role of exercise in airway inflammation in asthma is poorly understood. We aimed to evaluate the effects of an aerobic training program on eosinophil inflammation (primary aim) and nitric oxide (secondary aim) in patients with moderate or severe persistent asthma. METHODS: sixty-eight patients randomly assigned to either control (CG) or aerobic training (TG) groups were studied during the period between medical consultations. Patients in the CG (educational program + breathing exercises; N = 34) and TG (educational program + breathing exercises + aerobic training; N = 34) were examined twice a week during a 3-month period. Before and after the intervention, patients underwent induced sputum, fractional exhaled nitric oxide (FeNO), pulmonary function, and cardiopulmonary exercise testing. Asthma symptom free days were quantified monthly, and asthma exacerbation was monitored during 3 months of intervention. RESULTS: at 3 months, decreases in the total and eosinophil cell counts in induced sputum (P = 0.004) and in the levels of FeNO (P = 0.009) were observed after intervention only in the TG. The number of asthma symptom-free days and VO(2max) also significantly improved (P < 0.001), and lower asthma exacerbation occurred in the TG (P < 0.01). In addition, the TG presented a strong positive relationship between baseline FeNO and eosinophil counts as well as their improvement after training (r = 0.77 and r = 0.9, respectively). CONCLUSIONS: aerobic training reduces sputum eosinophil and FeNO in patients with moderate or severe asthma, and these benefits were more significant in subjects with higher levels of inflammation. These results suggest that aerobic training might be useful as an adjuvant therapy in asthmatic patients under optimized medical treatment. PMID- 20581720 TI - Effects of step rate manipulation on joint mechanics during running. AB - PURPOSE: the objective of this study was to characterize the biomechanical effects of step rate modification during running on the hip, knee, and ankle joints so as to evaluate a potential strategy to reduce lower extremity loading and risk for injury. METHODS: three-dimensional kinematics and kinetics were recorded from 45 healthy recreational runners during treadmill running at constant speed under various step rate conditions (preferred, +/- 5%, and +/- 10%). We tested our primary hypothesis that a reduction in energy absorption by the lower extremity joints during the loading response would occur, primarily at the knee, when step rate was increased. RESULTS: less mechanical energy was absorbed at the knee (P < 0.01) during the +5% and +10% step rate conditions, whereas the hip (P < 0.01) absorbed less energy during the +10% condition only. All joints displayed substantially (P < 0.01) more energy absorption when preferred step rate was reduced by 10%. Step length (P < 0.01), center of mass vertical excursion (P < 0.01), braking impulse (P < 0.01), and peak knee flexion angle (P < 0.01) were observed to decrease with increasing step rate. When step rate was increased 10% above preferred, peak hip adduction angle (P < 0.01) and peak hip adduction (P < 0.01) and internal rotation (P < 0.01) moments were found to decrease. CONCLUSION: we conclude that subtle increases in step rate can substantially reduce the loading to the hip and knee joints during running and may prove beneficial in the prevention and treatment of common running-related injuries. PMID- 20581721 TI - Identifying Walking Trips Using GPS Data. AB - PURPOSE: this study developed and tested algorithms to identify outdoor walking trips from portable global positioning system (GPS) units in free-living conditions. METHODS: the study included a calibration and a validation phase. For the calibration phase, we determined the best algorithm from 35 person-days of data. Measures of agreement regarding the daily number and duration of diary reported and GPS-identified trips were used. In the validation phase, the best algorithm was applied to an additional and separate 136 person-days of diary and GPS data. RESULTS: the preferred algorithm in the calibration phase resulted in 90% of trips identified from the GPS data being found in the diary, whereas 81% of trips reported in the diary being found in the GPS data. The preferred algorithm used 1) a maximum 3-min gap between points to define a trip, 2) at least 5 min or more of continuous GPS points, 3) a speed range between 2 and 8.0 km.h, 4) at least 30 m of displacement between the start and end points of a trip, and 5) merged walking trips when the time gap between trips was less than 3 min. With the validation data, substantial agreement between the GPS and the diary was achieved, with 86% of trips identified from the GPS data found in the diary and 77% of trips reported in the diary found in the GPS data. CONCLUSIONS: the algorithm identified free-living walking trips of more than 5 min in duration. The ability to identify outdoor walking trips from GPS data can be improved by reducing recording intervals used in the GPS units and monitoring participant compliance. Further research is desirable to determine whether concurrent wearing of an accelerometer may improve the ability to detect walking more accurately. PMID- 20581722 TI - Seasonal reduction in physical activity and flow-mediated dilation in children. AB - PURPOSE: cardiovascular disease is a process that has its origins in childhood. Endothelial dysfunction is the earliest detectable manifestation of cardiovascular disease. This study aimed to assess the impact of seasonal changes in physical activity (PA) and body composition on conduit artery endothelial function in children. METHOD: we studied 116 children (70 girls aged 10.7 +/- 0.3 yr and 46 boys aged 10.7 +/- 0.3 yr) on two occasions; in the northern summer (June) and late autumn (November). We assessed flow-mediated dilation (FMD) using high-resolution Doppler ultrasound. Body composition was measured by dual-energy x-ray absorptiometry. PA was assessed using accelerometry. RESULTS: FMD (10.0% +/ 4.3% to 7.9% +/- 3.9%, P < 0.001) and PA (94.1 +/- 34.8 to 77.8 +/- 33.7 min.d, P < 0.01) decreased, while percentage body fat increased (27.6% +/- 6.8% to 28.0% +/- 6.6%, P < 0.001) between summer and autumn. Decreases in FMD correlated with decreases in high-intensity PA (r = 0.23, P = 0.04), and change in high-intensity PA was the only predictor of change in FMD. No relationships were evident between changes in body composition and FMD. CONCLUSIONS: vascular function decreased between summer and autumn in this cohort. There were no relationships between change in FMD and changes in body composition or low/moderate-intensity PA. The associations between FMD and high-intensity PA suggests that future interventions should encourage this form of behavior, particularly at the times of year associated with lower PA. PMID- 20581723 TI - Effects of soy isoflavones and genistein on glucose metabolism in perimenopausal and postmenopausal non-Asian women: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: Several randomized controlled trials (RCTs) have examined the role of soy isoflavones on cardiovascular risk factors in perimenopausal and postmenopausal women and have yielded inconsistent results. This meta-analysis aimed to assess the overall effect of soy isoflavones on glucose metabolism: fasting blood glucose, insulin, and insulin resistance. METHODS: We searched for all articles published in English and indexed in Medline from January 1990 to December 2009. We included RCTs for soy isoflavone supplementation in perimenopausal and postmenopausal women not taking hormone therapy, selecting non Asian women only. The main outcomes were fasting blood glucose changes from baseline. RESULTS: We identified 10 eligible RCTs containing blood glucose data of 794 women. The main result was that soy isoflavones did not affect fasting blood glucose significantly. Under a random-effects model, the average difference in fasting blood glucose values between women assigned to isoflavones and women assigned to placebo was -2.16 mg/dL (95% CI, -5.21 to 0.89 mg/dL; P = 0.17). In genistein studies, the mean difference was -7.15 mg/dL (95% CI, -11.47 to -2.82). However, the effects on insulin and homeostasis model assessment insulin resistance were significant: -1.37 microIU/mL (95% CI, -1.92 to -0.81 microIU/mL) and -0.39 (95% CI, -0.65 to -0.14), respectively. Subgroup analyses did not show a significant effect of isoflavone dose, whereas isoflavone mixtures and genistein had a different effect on fasting blood glucose. CONCLUSIONS: This meta analysis of RCTs showed that isoflavone use was not associated with a significant glycemia reduction in perimenopausal and postmenopausal non-Asian women. However, the few studies that reported insulin and homeostasis model assessment insulin resistance changes suggested that soy isoflavones and genistein alone had a beneficial effect on glucose metabolism. PMID- 20581724 TI - Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: Hot flashes are a major quality-of-life issue for breast cancer survivors, interrupting sleep, reducing quality of life, and diminishing treatment adherence to adjuvant endocrine therapies. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are used widely but are only partially effective for hot flashes. Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life. METHODS: Women with breast cancer or at high risk for developing the disease who had hot flashes in association with nocturnal awakenings were randomized to double-blinded treatment with zolpidem 10 mg or placebo for 5 weeks. SSRI/SNRI nonusers (81%) started venlafaxine XR 75 mg/day concurrently, whereas SSRI/SNRI users continued that therapy. We compared the proportion of responders, defined as study completers with improved subjective sleep quality (Pittsburgh Sleep Quality Index) and/or objectively assessed wake time after sleep onset on actigraphy, between groups. RESULTS: Of 53 women (aged 51 +/- 8 y) randomized to zolpidem augmentation (n = 25) or placebo augmentation (n = 28), 38 completed the protocol (57% on placebo, 88% on zolpidem). More women augmented with zolpidem than placebo were responders on the sleep outcome (40% vs 14%; P = 0.035). Quality of life improved more with zolpidem than with placebo (P = 0.01). Treatment effects on hot flashes and mood did not differ between groups. CONCLUSIONS: Augmentation of SSRI/SNRI with zolpidem improves sleep and quality of life in breast cancer survivors with hot flashes and associated sleep disturbance. Adding a hypnotic agent to an SSRI/SNRI helps women to sleep through nighttime hot flashes. Treatments targeting sleep may be an important supplemental strategy to optimize well-being. PMID- 20581725 TI - Differential functions of NR2A and NR2B in short-term and long-term memory in rats. AB - N-methyl-D-aspartate receptors (NMDARs) are glutamate receptors implicated in synaptic plasticity and memory function. The specific functions of NMDA receptor subunits NR2A and NR2B have not yet been fully determined in the different types of memory. Nine Wistar rats (8-weeks-old) were subjected to the Morris water maze task to evaluate the memory behaviorally. Quantitative analysis of NR1, NR2A, and NR2B levels in the right and left forebrain of rats was performed and subunit associations with different types of memory were investigated using the Morris water maze task. Right forebrain NR2A expression was significantly increased and correlated with faster escape time onto a hidden platform, indicating involvement of short-term memory, because of the training time interval. Right forebrain NR2B expression was positively associated with long-term memory lasting 24-h (h). In the left forebrain, NR2B expression was positively related to 72-h long-term memory. In conclusion, the functions of NR2A and NR2B receptors were differentially specialized in short-term and long-term memory, depending on the right or left forebrain. PMID- 20581726 TI - Intra- and intersession repeatability of a double-pass instrument. AB - PURPOSE: To evaluate the intra- and intersession repeatability of the optical quality parameters provided by the Optical Quality Analysis System (OQAS), which is based on the double-pass technique. METHODS: We performed optical quality measurements using the OQAS on 20 eyes of 10 healthy subjects who had best spectacle-corrected visual acuity of 20/20 or better. Measurements were performed by the same examiner in three different sessions that were separated by 10-min intervals. The subject's eye was realigned at the beginning of each session. During each session, three consecutive measurements were taken without realignment. The following optical quality parameters were analyzed: the modulation transfer function cutoff frequency (MTFcutoff), the Strehl ratio, the OQAS values (OV) at contrasts of 100%, 20%, and 9%, and the objective scatter index (OSI). RESULTS: The mean coefficients of repeatability obtained for the first session were 4.51 (MTFcutoff), 0.049 (Strehl ratio), 0.15 (OV 100%), 0.21 (OV 20%), 0.28 (OV 9%), and 0.11 (OSI), which were similar to those found in the second and third sessions. The confidence limits in the Bland and Altman charts when the intrasession repeatability was assessed (in a comparison of the first and second measurements of the first session) ranged from -3.16 to 3.94 (MTFcutoff), -0.060 to 0.069 (Strehl ratio), -0.12 to 0.18 (OV 100%), -0.20 to 0.23 (OV 20%), -0.29 to 0.27 (OV 9%), and -0.12 to 0.13 (OSI). The same limits when the intersession repeatability was assessed (in a comparison of the first and second sessions) ranged from -5.30 to 5.49 (MTFcutoff), -0.054 to 0.050 (Strehl ratio), -0.17 to 0.17 (OV 100%), -0.22 to 0.19 (OV 20%), -0.26 to 0.29 (OV 9%), and -0.12 to 0.13 (OSI). CONCLUSIONS: Our findings showed that OQAS is a clinical instrument with a good intra- and intersession repeatability and that the realignment of the eye does not introduce any additional variability in the measurements. PMID- 20581727 TI - The Charles F. Prentice award lecture 2009: Crystalline lens research and serendipity in science. AB - Whether it is called serendipity or creativity, the process of scientific discovery is not one that lends itself to advance planning or programming, nor does it lend itself to an emphasis solely on applied research, research with industrial partners, or large teams of researchers because researchers must rely on intuition and the capacity to move quickly in new directions. Studies in my laboratory began with efforts to relate lens embryonic development to lens optical performance in a variety of vertebrate species. The initial direction concerned the optics of the fish eye, a system in which a spherical lens is essentially the only refractive component of the eye and one in which accommodation takes place by means of lens movement. This in turn led to an interest in how amphibious animals cope with the refractive transition that takes place when moving from air to water and vice versa. The development of a super accommodative ability in some diving birds is one adaptation that was explored. These curiosity-driven efforts led in turn to the development of a scanning laser system that provided a tool that can be used to evaluate the process of cataract development, either on the basis of in vivo exposure to chemicals or electromagnetic radiation and subsequent analysis of the excised lens or to the in vitro study of the lens in long-term whole lens culture experiments. The same approach has also been used as an in vitro ocular toxicology assay to develop sensitive in vitro methods to reduce regulatory dependence on the use of live animals. Finally, these applied directions in turn created new basic knowledge concerning the morphology and physiology of eye tissue organelles, particularly the morphology, distribution, and dynamic properties of the mitochondria found in the lens and in the retinal pigment epithelium. PMID- 20581728 TI - If Arielle were Italian. PMID- 20581729 TI - Physicians' experiences and perspectives regarding follow-up meetings with parents after a child's death in the pediatric intensive care unit. AB - OBJECTIVE: To investigate critical care physicians' experiences and perspectives regarding follow-up meetings with parents after a child's death in the pediatric intensive care unit. Parents of children who die in the pediatric intensive care unit often desire a follow-up meeting with the physicians who cared for their child. DESIGN: Semistructured, audio-recorded telephone interviews. SETTING: Six clinical centers affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PARTICIPANTS: Seventy critical care physicians (i.e., attendings and fellows) practicing or training at a Child Health and Human Development Collaborative Pediatric Critical Care Research Network clinical center between February 1, 2008 and June 30, 2008. MEASUREMENTS AND MAIN RESULTS: Twenty-three (33%) physicians reported never participating in a follow-up meeting with bereaved parents; 22 (31%) participated in one to five meetings; and 25 (36%) participated in more than five meetings. Of those with prior experience, 44 (94%) met with parents at the hospital and 40 (85%) met within 3 months of the death. Meeting content included discussing autopsy, parent questions, hospital course, cause of death, genetic risk, bereavement services, and legal or administrative issues; providing emotional support; and receiving parent feedback. Forty (85%) physicians perceived the meetings to be beneficial to families, and 35 (74%) to physicians. Barriers included time and scheduling, family and physician unwillingness, distance and transportation, language and cultural issues, parent anger, and lack of a system for meeting initiation and planning. CONCLUSIONS: Critical care physicians have a wide range of experience conducting follow-up meetings with bereaved parents. Although physicians perceive benefits to follow up meetings, barriers exist that interfere with their implementation in clinical practice. PMID- 20581730 TI - Ultrasound findings in Plasmodium falciparum malaria: a pilot study. AB - OBJECTIVE: To investigate whether hand-carried ultrasound technology may be valuable in the assessment of children with acute malaria. Every year, approximately 800,000 children under the age of 5 yrs die of complications of Plasmodium falciparum malaria infection. The advent of hand-carried ultrasound technology has made diagnostic ultrasonography possible in underresourced settings. DESIGN: We performed a pilot observational study collecting clinical data and performing ultrasound examinations on children diagnosed with P. falciparum malaria infection. The targeted ultrasound examination included measurement of optic nerve sheath diameter, color transcranial Doppler insonation of the cerebral vasculature, cardiac ultrasound, and abdominal ultrasound. SETTING: Pediatric acute care unit of Mulago Hospital in Kampala, Uganda. PATIENTS: Thirty-three hospitalized children between the ages of 6 months and 12 yrs with documented acute P. falciparum infection. INTERVENTION: Targeted bedside ultrasound examination. MEASUREMENTS AND MAIN RESULTS: Increased optic nerve sheath diameter was observed in one third of all patients with malaria and in 100% of the patients diagnosed with cerebral malaria. Although higher-than-normal cerebral blood flow velocities were demonstrated in three (25%) of 12 patients with severe anemia, most patients demonstrated a normal cerebral blood flow velocity, suggesting a blunted response to anemia. We did not find evidence of pulmonary hypertension by cardiac ultrasound, and cardiac function did not seem depressed, even among patients with severe anemia and lactic acidosis. Finally, spleen size as determined by palpation significantly overestimated the true incidence of splenomegaly as measured by ultrasound (48% and 24%, respectively). CONCLUSIONS: A targeted ultrasound examination focusing on optic nerve sheath diameter, color transcranial Doppler, cardiac ultrasound, and spleen size may prove useful for patient classification, risk stratification, research studies, and treatment monitoring in pediatric malaria. More studies should be done. PMID- 20581731 TI - Tracheal tube airleak in clinical practice and impact on tidal volume measurement in ventilated neonates. AB - OBJECTIVE: To determine the prevalence, size, and factors affecting tracheal tube (TT) leak in clinical practice and their influence on the displayed tidal volume (Vt) in ventilated newborn infants using uncuffed TTs. Monitoring of Vt is important for implementation of lung-protective ventilation strategies but becomes meaningless in the presence of large TT airleaks. DESIGN: Retrospective clinical study. SETTING: Neonatal intensive care unit. PATIENTS: Patient records of 163 neonates ventilated with Babylog 8000 for >= 5 hrs with a median (range) gestation age of 31.1 wks (23.3-41.9 wks) and a median birth weight of 1470 g (410-4475 g) were evaluated. INTERVENTIONS: : Ventilatory settings, TT leak, and Vt were recorded every 3 hrs. The lowest, median, and highest TT leaks were noted on the day the first TT leak (>5%) occurred, the day on which TT leak peaked, and the day of extubation. MEASUREMENTS AND MAIN RESULTS: A TT leak of >5% was seen in 122 (75%) infants. Neonates with TT leak, compared with those without TT leak, had a longer duration of mechanical ventilation (p < .001), a lower gestational age (p = .004), a reduced birth weight (p = .005), and a higher prevalence of reintubation (p = .003). The greatest TT leak was seen in infants ventilated with a TT of <3-mm diameter. During the entire duration of mechanical ventilation, 42.3% of all neonates experienced at least one TT leak of >40% commonly seen on the third day of mechanical ventilation. Regression analysis showed that a TT leak of 40% indicated that the displayed Vt was underestimated by 1.2 mL/kg (about 24% of target Vt). CONCLUSIONS: TT leak is highly variable, and TT leak of >40% with clinically relevant Vt errors occurred in nearly half of all ventilated neonates. Preterm infants of low birth weight and with small-diameter TTs ventilated for a long period were at greater risk of TT leak. PMID- 20581732 TI - Performance of the Pediatric Index of Mortality 2 for pediatric cardiac surgery patients. AB - OBJECTIVE: To evaluate the performance of the Pediatric Index of Mortality 2 (PIM 2) for pediatric cardiac surgery patients admitted to the pediatric intensive care unit (PICU). DESIGN: : Retrospective cohort analysis. SETTING: Multi institutional PICUs. PATIENTS: Children whose PICU admission had an associated cardiac surgical procedure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance of the PIM-2 was evaluated with both discrimination and calibration measures. Discrimination was assessed with a receiver operating characteristic curve and associated area under the curve measurement. Calibration was measured across defined groups based on mortality risk, using the Hosmer-Lemeshow goodness of-fit test. Analyses were performed initially, using the entire cohort, and then based on operative status (perioperative defined as procedure occurring within 24 hrs of PICU admission and preoperative as occurring >24 hrs from the time of PICU admission). A total of 9,208 patients were identified as cardiac surgery patients with 8,391 (91%) considered as perioperative. Average age of the entire cohort was 3.3 yrs (median, 10 mos, 0-18 yrs), although preoperative children tended to be younger (median, <1 month). Preoperative patients also had longer PICU median lengths of stay than perioperative patients (12 days [1-375 days] vs. 3 days [1 369 days], respectively). For the entire cohort, the PIM-2 had fair discrimination power (area under the curve, 0.80; 95% confidence interval, 0.77 0.83) and poor calibration (p < .0001). Its predictive ability was similarly inadequate for quality assessment (standardized mortality ratio, 0.81; 95% confidence interval, 0.72-0.90) with significant overprediction in the highest decile risk group. For the subpopulations, the model continued to perform poorly with low area under the curves for preoperative patients and poor calibration for both groups. PIM-2 tended to overpredict mortality for perioperative patients and underpredict for preoperative patients (standardized mortality ratios, 0.69 [95% confidence interval, 0.59-0.78] and 1.48 [95% confidence interval, 1.27-1.70], respectively). CONCLUSIONS: The PIM-2 demonstrated poor performance with fair discrimination, poor calibration, and predictive ability for pediatric cardiac surgery population and thus cannot be recommended in its current form as an adequate adjustment tool for quality measurement in this patient group. PMID- 20581733 TI - Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation. AB - OBJECTIVE: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation are lacking. DESIGN: Prospective longitudinal cohort study. SETTING: Outpatient clinic of a tertiary level pediatric hospital. PATIENTS: The cohort consisted of 64 infants; 33 received extracorporeal membrane oxygenation for meconium aspiration syndrome, 14 for congenital diaphragmatic hernia, four for sepsis, six for persistent pulmonary hypertension of the neonate, and seven for respiratory distress syndrome of infancy. Evaluation was at 6 mos and 12 mos; 39 infants were evaluated at both time points . INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional residual capacity and forced expiratory flow at functional residual capacity were measured and expressed as z score. Mean (sem) functional residual capacities in z score were 0.0 (0.2) and 0.2 (0.2) at 6 mos and 12 mos, respectively. Mean (sem) forced expiratory flow was significantly below average (z score = 0) (p < .001) at 6 mos and 12 mos: -1.1 (0.1) and -1.2 (0.1), respectively. At 12 mos, infants with diaphragmatic hernia had a functional residual capacity significantly above normal: mean (sem) z score = 1.2 (0.5). CONCLUSIONS: Infants treated with extracorporeal membrane oxygenation have normal lung volumes and stable forced expiratory flows within normal range, although below average, within the first year of life. There is reason to believe, therefore, that extracorporeal membrane oxygenation either ameliorates the harmful effects of mechanical ventilation or somehow preserves lung function in the very ill neonate. PMID- 20581734 TI - Simulation-based mock codes significantly correlate with improved pediatric patient cardiopulmonary arrest survival rates. AB - OBJECTIVE: To evaluate the viability and effectiveness of a simulation-based pediatric mock code program on patient outcomes, as well as residents' confidence in performing resuscitations. A resident's leadership ability is integral to accurate and efficient clinical response in the successful management of cardiopulmonary arrest (CPA). Direct experience is a contributing factor to a resident's code team leadership ability; however, opportunities to gain experience are limited by relative infrequency of pediatric arrests and code occurrences when residents are on service. DESIGN: Longitudinal, mixed-methods research design. SETTING: Children's hospital at an tertiary care academic medical center. PATIENTS: Pediatric. INTERVENTIONS: Clinicians responsible for pediatric resuscitations responded to mock codes randomly called at increasing rates over a 48-month period, just as they would an actual CPA event. Events were recorded and used for immediate debriefing facilitated by clinical faculty to provide residents feedback about their performance. MEASUREMENTS: Self-assessment data were collected from all team members. Hospital records for pediatric CPA survival rates were examined for the study duration. RESULTS: Survival rates increased to approximately 50% (p = .000), correlating with the increased number of mock codes (r = .87). These results are significantly above the average national pediatric CPA survival rates and held steady for 3 consecutive years, demonstrating the stability of the program's outcomes. CONCLUSIONS: This study suggests that a simulation-based mock code program may significantly benefit pediatric patient CPA outcomes-applied clinical outcomes-not simply learner perceived value, increased confidence, or simulation-based outcomes. The use of mock codes as an integral part of residency programs could provide residents with the resuscitation training they require to become proficient in their practice. Future programs that incorporate transport scenarios, ambulatory care, and other outpatient settings could further benefit pediatric patients in prehospital contexts. PMID- 20581735 TI - Catheter-related bacteremia caused by methicillin-resistant coagulase negative staphylococci with elevated minimal inhibitory concentration for vancomycin. AB - Treatment of bacteremia caused by methicillin-resistant coagulase-negative staphylococci with vancomycin minimum inhibitory concentration >=2 mg/L frequently requires central venous catheter removal in children with cancer. There are few data supporting efficacy and safety of antibiotic catheter lock or use of daptomycin or linezolid for this indication in children. PMID- 20581736 TI - Prospective characterization of norovirus compared with rotavirus acute diarrhea episodes in chilean children. AB - BACKGROUND: Rotavirus and more recently noroviruses are recognized as main causes of moderate to severe acute diarrhea episodes (ADE) in children < or =5 years of age. Comparing epidemiologic and clinical features of norovirus to rotavirus ADE will aid in the decision-making process required to develop norovirus vaccines. METHODS: Surveillance for ADE occurring in children < or =5 years of age was implemented in the emergency department (ED) and ward of a large hospital in Santiago and Valparaiso, and in 4 outpatient clinics in Santiago. A stool sample was obtained within 48 hours of consultation for rotavirus detection by enzyme linked immunosorbent assay and noroviruses by enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction. For ED and hospital rotavirus and norovirus ADE parents were instructed to monitor clinical findings associated with severity until the end of the episode. The 20-point Vesikari score was used to determine disease severity. RESULTS: Between July 2006 and October 2008 rotavirus and noroviruses were detected in 331 (26%) and 224 (18%) of 1913 ADE evaluated. The proportion of rotavirus-positive samples in hospital ward, ED, and outpatient clinic was 40%, 26% to 30%, and 13% compared with 18%, 17% to 19%, and 14% for noroviruses. Mean age and 25%-75% interquartile interval of children with rotavirus and norovirus ADE were remarkably similar, 15.6 months (9-20), and 15.5 months (9-19), respectively. Rotavirus cases displayed an autumn-winter peak followed 2 to 3 months later by the norovirus peak. The mean (interquartile) for the Vesikari score was 12.9 (11-15) and 11.9 (9-14.5) for rotavirus (N = 331) and norovirus (N = 224) ADE, respectively, P = 0.003. Compared with norovirus, rotavirus ADE were more common in the 11 to 16 severity score interval (P = 0.006), had a higher maximum stool output in a given day (P = 0.01) and more frequent fever (P < 0.0001). Duration of diarrhea, presence, duration and intensity of vomiting, and intensity of fever did not differ between viruses. Mixed rotavirus and norovirus infections were uncommon (<1%) and not clinically more severe. Clinical severity of ADE in young infants was similar for rotavirus and lower (P = 0.03) for noroviruses compared with older children. CONCLUSION: Noroviruses are a significant cause of moderate to severe endemic ADE in Chilean children. Although significantly less severe than rotavirus as a group, most norovirus episodes were moderate to severe clinically. An effective norovirus vaccine would be of significant additional benefit to the current rotavirus vaccine in decreasing disease burden associated with ADE. PMID- 20581737 TI - Weekly cyclodextrin administration normalizes cholesterol metabolism in nearly every organ of the Niemann-Pick type C1 mouse and markedly prolongs life. AB - Niemann-Pick type C1 (NPC1) disease arises from a mutation inactivating NPC1 protein that normally moves unesterified cholesterol from the late endosomal/lysosomal complex of cells to the cytosolic compartment for processing. As a result, cholesterol accumulates in every tissue of the body causing liver, lung, and CNS disease. Treatment of the murine model of this disease, the npc1 mouse, s.c. with beta-cyclodextrin (4000 mg/kg) one time each week normalized cellular cholesterol metabolism in the liver and most other organs. At the same time, the hepatic dysfunction seen in the untreated npc1 mouse was prevented. The severity of cerebellar neurodegeneration also was ameliorated, although not entirely prevented, and the median lifespan of the animals was doubled. However, in contrast to these other organs, lung showed progressive macrophage infiltration with development of lipoid pneumonitis. These studies demonstrated that weekly cyclodextrin administration overcomes the lysosomal transport defect associated with the NPC1 mutation, nearly normalizes hepatic and whole animal cholesterol pools, and prevents the development of liver disease. Furthermore, this treatment slows cerebellar neurodegeneration but has little or no effect on the development of progressive pulmonary disease. PMID- 20581738 TI - Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers relationship to microbial pressure and infant allergy. AB - The immune system of the neonate is influenced by maternal immunity during pregnancy and lactation. An altered microbial exposure, possibly underlying the increase of allergic diseases in affluent societies, may affect maternal breast milk immune composition. Secretory IgA (SIgA), IL-4, IL-10, IL-13, IFN-[gamma], TGF-[beta]1, and TGF-[beta]2 were analyzed with ELISA in colostrum and 1-mo mature milk from mothers from Estonia (n = 39) and Sweden (n = 60), the two geographically adjacent countries with different living conditions and allergy incidence. The IL-10 and IFN-[gamma] levels were higher in colostrum from Estonian than Swedish mothers, whereas the opposite was true for TGF-[beta]2. In mature milk, higher SIgA and IFN-[gamma] levels but lower TGF-[beta]1 and TGF [beta]2 levels were observed in Estonian than Swedish mothers. Interestingly, in Sweden but not Estonia, the TGF-[beta]1 and TGF-[beta]2 levels correlated inversely with environmental endotoxin concentrations, whereas positive correlations to microbial load were observed for IL-4, IL-10, and IFN-[gamma]. High colostral IL-13 levels were associated with allergic sensitization during infancy in Sweden. In conclusion, Estonian mothers have lower breast milk levels of TGF-[beta], particularly TGF-[beta]2, but higher levels of SIgA, IL-10, and IFN-[gamma] than Swedish mothers, possibly because of differences in microbial load. PMID- 20581739 TI - A mouse model of conduction system patterning abnormalities in heterotaxy syndrome. AB - Duplication or absence of parts of the specialized cardiac conduction system in patients with heterotaxy syndrome causes significant clinical disease, but the mechanistic basis by which embryonic disruption of left-right patterning alters conduction system patterning in these patients is not well understood. We sought to determine whether a mouse model of X-linked human heterotaxy recapitulates conduction system abnormalities identified in patients with heterotaxy. Cardiac structure and conduction system patterning were evaluated in Zic3 null embryos from e9.5 to e16.5 using genetic and molecular methods. Severe structural abnormalities involving atrial, ventricular, and conotruncal development were associated with a spectrum of disorganized and ambiguous arrangements throughout the conduction system, including the appearance of duplicated structures. The severity and location of conduction system abnormalities correlated with the severity and location of associated structural heart disease and were identifiable at the earliest stages examined. The Zic3 mouse model provides a novel tool to dissect the mechanistic underpinnings of conduction system patterning and dysfunction and its relationship to cardiovascular malformations, making it a promising model to improve understanding and risk assessment in the clinical arena. PMID- 20581740 TI - Antenatal betamethasone alters vascular reactivity in adult female ovine cerebral arteries. AB - Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta exposed and control sheep, whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there seemed to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep. PMID- 20581741 TI - Patterns of gene expression in the ductus arteriosus are related to environmental and genetic risk factors for persistent ductus patency. AB - Three independent risk factors (immature gestation, absence of antenatal glucocorticoid exposure, and presence of the rs2817399(A) allele of the gene TFAP2B) are associated with patent ductus arteriosus (PDAs) that fail to close during prostaglandin inhibition. We hypothesized that these three factors may affect a common set of genes that increase the risk of persistent PDA after birth. We studied baboon ductus from term, preterm, and glucocorticoid-treated preterm fetuses and found that both immature gestation and absence of antenatal glucocorticoid exposure decreased RNA expression of calcium- and potassium channel genes involved in oxygen-induced constriction, and phosphodiesterase genes (that modulate cAMP/cGMP signaling). Ductus obtained from second trimester human pregnancies were genotyped for TFAP2B polymorphisms. When present, the rs2817399(A) allele also was associated with decreased expression of calcium- and potassium-channel genes. In contrast, alleles of two other TFAP2B polymorphisms, rs2817419(G) and rs2635727(T), which are not related to the incidence of PDA after birth, had no effect on RNA expression. In conclusion, three calcium- and potassium-channel genes (CACNA1G/ alpha1G, CACNB 2/CaL-beta2, and KCNA2/ Kv1.2) were similarly affected by each of the PDA risk factors. We speculate that these channels may play a significant role in closing the preterm ductus during prostaglandin inhibition and may be potential targets for future pharmacologic manipulations. PMID- 20581743 TI - Identification of GATA6 sequence variants in patients with congenital heart defects. AB - Although the etiology for the majority of congenital heart disease (CHD) remains poorly understood, the known genetic causes are often the result of mutations in cardiac developmental genes. GATA6 encodes for a cardiac transcription factor, which is broadly expressed in the developing heart and is critical for normal cardiac morphogenesis, making it a candidate gene for congenital heart defects in humans. The objective of this study was to determine the frequency of GATA6 sequence variants in a population of individuals with a spectrum of cardiac malformations. The coding regions of GATA6 were sequenced in 310 individuals with CHD. We identified two novel sequence variations in GATA6 that altered highly conserved amino acid residues (A178V and L198V) and were not found in a control population. These variants were identified in two individuals (one with tetralogy of Fallot and the other with an atrioventricular septal defect in the setting of complex CHD). Biochemical studies demonstrate that the GATA6 A178V mutant protein results in increased transactivation ability when compared with wild-type GATA6. These data suggest that nonsynonymous GATA6 sequence variants are infrequently found in individuals with CHD. PMID- 20581742 TI - Ibuprofen treatment for closure of patent ductus arteriosus is not associated with increased risk of neuropathology. AB - Ibuprofen is an effective pharmacological intervention for closure of a patent ductus arteriosus (PDA) in preterm infants and is an alternative to surgical ligation; however, it is not certain whether ibuprofen treatment is associated with adverse effects on the brain. Therefore, this study examined neuropathological outcomes of ibuprofen therapy for a PDA. Fetal baboons were delivered at 125 d of gestation (dg; term ~185 dg) by caesarean section, given surfactant, and ventilated for 14 d with positive pressure ventilation (PPV). Baboons were randomly allocated to receive either ibuprofen (PPV+ ibuprofen, n = 8) or no therapy (PPV, n = 5). Animals were killed on day 14 and brains assessed for cerebral growth, development, and neuropathology. Body and brain weights, the total volume of the brain, and the surface folding index (measure of brain growth) were not different (p > 0.05) between PPV+ ibuprofen-treated and PPV animals. There was no difference (p > 0.05) in the number of myelin basic protein immunoreactive (IR) oligodendrocytes, glial fibrillary acid protein-IR astrocytes, or Iba1-IR macrophages/microglia in the forebrain. No overt cerebellar alterations were observed in either group. Ibuprofen treatment for PDA closure in the preterm baboon neonate is not associated with any increased risk of neuropathology or alterations to brain growth and development. PMID- 20581745 TI - Selective Toll--like receptor expression in human fetal lung. AB - Toll-like receptors (TLRs) are critical components of the innate immune system, acting as pattern recognition molecules and triggering an inflammatory response. TLR associated gene products are of interest in modulating inflammatory-related pulmonary diseases of the neonate. The ontogeny of TLR-related genes in human fetal lung has not been previously described and could elucidate additional functions and identify strategies for attenuating the effects of fetal inflammation. We examined the expression of 84 TLR-related genes on 23 human fetal lung samples from three groups with estimated ages of 60 (57-59 d), 90 (89 91 d), and 130 (117-154 d) d. By using a false detection rate algorithm, we identified 32 genes displaying developmental regulation with TLR2 having the greatest up-regulation of TLR genes (9.2-fold increase) and TLR4 unchanged. We confirmed the TLR2 up-regulation by examining an additional 133 fetal lung tissue samples with a fluorogenic polymerase chain reaction assay (TaqMan) and found an exponential best-fit curve during the study time. The best-fit curve predicts a 6.1-fold increase from 60 to 130 d. We conclude that TLR2 is developmentally expressed from the early pseudoglandular stage of lung development to the canalicular stage. PMID- 20581744 TI - [13C]Methionine breath test to assess intestinal failure-associated liver disease. AB - Oxidation of L[1-C]methionine ([C]-Met) in liver mitochondria can be quantified by measuring exhaled CO2. We hypothesized that CO2 recovery after i.v. administered [C]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-C]-Met breath tests ([C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for CO2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO2) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [C]-MBT may also help quantify progression or improvement of IFALD. PMID- 20581746 TI - Effect of antenatal betamethasone administration on neonatal cardiac autonomic balance. AB - Beneficial effects of antenatal glucocorticoid treatment in pregnancies at risk for preterm delivery may entail long-term consequences for the establishment of sympathoadrenergic system balance. We analyzed the cardiac autonomic system activity in neonates with a single course of antenatal betamethasone (2 * 12 mg) treatment by calculating heart rate variability (HRV) time-domain parameters from 24 h ECG recordings and short-term frequency-domain parameters during infant active and resting states. In addition, resting and challenged salivary alpha amylase levels were measured in 23 betamethasone-exposed neonates and compared with controls. Indicators for overall HRV (SDNN: p = 0.258; triangular index: p = 0.179) and sympathovagal balance [low- to high-frequency power (LF/HF): p = 0.82 (resting state)] were not significantly different in neonates of the betamethasone treatment group. Parameters mostly influenced by sympathetic activity [SD of the average of valid NN intervals (SDANN): p = 0.184 and SDs of all NN intervals (SDNNi): p = 0.784] and vagal tone [RMSSD: p = 1.0; NN50: p = 0.852; HF: p = 0.785 (resting state)] were unaltered. Resting alpha-amylase levels were not significantly different in the betamethasone treatment group (p = 0.304); however, alpha-amylase release after a neonatal challenge was slightly reduced (p = 0.045). Thus, cardiac autonomic balance seems to be preserved in neonates exposed to a single course of antenatal betamethasone treatment. PMID- 20581747 TI - Association of interleukin-1 receptor antagonist gene polymorphism with response to conservative treatment of lumbar herniated nucleus pulposus. AB - STUDY DESIGN: A case-control study. OBJECTIVE: To evaluate the relationship between gene polymorphism in interleukin 1 receptor antagonist (IL1RN) and response to conservative treatment of lumbar herniated nucleus pulposus (HNP). SUMMARY OF BACKGROUND DATA: There had been several studies on IL1RN polymorphism related with incidence of disc degeneration or back pain but, there had been no report on clinical features of lumbar HNP. METHODS: We analyzed the variable number tandem repeat polymorphism of IL1RN genes in 54 single level subligamentous extruded lumbar HNP patients and compared allele frequency and incidence of heterozygote with 227 healthy adult controls. Within HNP group, we compared 2 groups; surgery group and conservative treatment group according to response to conservative treatment. RESULTS: The prevalence of A1 (odd ratio = 0.45, P = 0.0009) and A3 (odd ratio = 3.86, P = 0.0006) was significantly higher in HNP group than control group. The allele frequency of A1, A2, A3, A4, and A5 were 84.2:84.6, 7.3:15.4, 8.5:0, 0:0, 0:0, respectively, in surgical and conservative treatment group. The allele frequency for A3 was found significantly higher in the surgery group than in the conservative treatment group. CONCLUSION: These results suggest that a high allele prevalence of A3 contribute to the clinical progression and the response to conservative treatment for lumbar HNP. IL1RN gene polymorphism may affect the clinical course of lumbar HNP. PMID- 20581748 TI - The effect of umbilical cord blood cells on outcomes after experimental traumatic spinal cord injury. AB - STUDY DESIGN: A cytokine expression profile of umbilical cord blood (UCB) derived multipotential stem cells (MPSC) was produced. We then transplanted MPSCs into a rat model of spinal cord injury (SCI) and assessed neurologic function as well as spinal cord histology. OBJECTIVE: To determine if MPSCs transplanted into a rat model of acute SCI would lead to a beneficial neurologic effect. SUMMARY OF BACKGROUND DATA: Conditioned medium from UCB contains factors that could promote healing of endogenous neural tissues. Previously, our laboratory has demonstrated that UCB hematopoietic cells can develop into MPSCs capable of differentiating into multiple cell types including oligodendrocyte-like cells. METHODS: We cultured MPSCs from UCB cells using fibroblast growth factor 4, stem cell factor and fms-like tyrosine kinase receptor-3 ligand supplemented serum-free medium. Using a cytokine antibody array, we produced a cytokines expression profile of MPSCs. We then transplanted MPSCs into an immunosuppressed rat model of SCI and assessed neurologic function weekly for 6 weeks by the Basso, Beattie, and Bresnahan locomotor test. The spinal cords were examined histologically and lesion areas quantified. RESULTS: We detected elevated levels of cytokines and growth factors with known neuroprotective, angiogenic, and anti-inflammatory effects in the MPSC conditioned media. The SCI rats treated with MPSCs showed a significant improvement in Basso, Beattie, and Bresnahan scores after 6 weeks compared with the group that received vehicle only. Immunohistochemistry revealed transplanted human cells were present in the injured spinal cord after 1 week, but were no longer present by 6 weeks. There was a trend for the lesion size in treated rats to be smaller than that of the control group. CONCLUSION: We conclude that UCB MPSCs improve neurologic function of rats with acute SCI, possibly by the release of factors that reduce secondary injury. PMID- 20581749 TI - Rheology of intervertebral disc: an ex vivo study on the effect of loading history, loading magnitude, fatigue loading, and disc degeneration. AB - STUDY DESIGN: An ex vivo biomechanical study on the rheological properties of healthy porcine and degenerated human intervertebral disc. OBJECTIVE: To quantify the effect of loading history, loading magnitude, fatigue loading, and degeneration on disc rheology. SUMMARY OF BACKGROUND DATA: Disc rheological parameters, i.e., the aggregate modulus (HA) and hydraulic permeability (k) regulate the mechanical and biologic function of disc. The knowledge of effects of loading condition and degeneration on disc rheology can be beneficial for the design of new disc/nucleus implants or therapy. METHODS: The following 4 phases of experiments were conducted to find the changes of disc rheological properties: (1) Effect of loading history during 1-hour creep (640 N) and relaxation (20% strain) test. (2) Effect of loading magnitude (420 N vs. 640 N) during the creep test. (3) Effect of fatigue loading (420 N, 5 Hz for 0.5, 1, and 2 hours) on the creep loading behavior. (4) Difference of healthy porcine and degenerated human discs during creep loading. The experimental data were fitted with linear biphasic model. RESULTS: The aggregate modulus increased but hydraulic permeability decreased during creep loading. The aggregate modulus decreased but the hydraulic permeability did not change significantly during relaxation loading. The higher creep loading increased the aggregate modulus but decreased the hydraulic permeability. The fatigue loading did not change the aggregate modulus significantly, but decreased hydraulic permeability. Comparing the degenerated human disc to the healthy porcine disc, the aggregate modulus was higher but the hydraulic permeability was lower. CONCLUSION: The external loading and degeneration induce disc structural changes, e.g., the disc water content and interstitial matrix porosity, hence affect the disc rheological properties. The increase of aggregate modulus may be due to the reduction of disc hydration level, whereas the decrease of hydraulic permeability may be because of the shrinkage of disc matrix pores. PMID- 20581750 TI - An in vitro biotribological assessment of NUBAC, a polyetheretherketone-on polyetheretherketone articulating nucleus replacement device: methodology and results from a series of wear tests using different motion profiles, test frequencies, and environmental conditions. AB - STUDY DESIGN: In vitro biotribological investigation. OBJECTIVE: To evaluate the wear resistance and long-term biodurability of NUBAC, a PEEK-on-PEEK articulating nucleus replacement device, using a series of wear tests with different motion profiles, test frequencies, and environmental conditions. SUMMARY OF BACKGROUND DATA: Wear resistance is critical for any disc arthroplasty device, and osteolysis remains a clinical concern. The use of PEEK for an articulating load bearing nucleus replacement device represents a unique application of this material. NUBAC has an inner ball/socket articulation for motion, similar to total disc replacements. American Society for Testing and Materials and International Organization for Standardization have recommended wear testing methodologies for total disc replacements, however, they have not been clinically validated. Therefore, a series of wear tests were performed to characterize the wear properties of the device. METHODS: Four groups of devices were evaluated. Group 1 consisted of +/-7.5 degrees flexion/extension to 10 million cycles (Mc) followed by +/-7.5 degrees lateral bending to 10 Mc, alternated to 40 Mc. Groups 2 to 4 consisted of International Organization for Standardization motion and load profiles to 10 Mc, except Group 3 incorporated frequency shifting to ensure a nonrepetitive load and motion profile. Group 4 underwent simulated aging. All studies incorporated a load magnitude of 225 to 1024 N. The average wear rates were determined using linear regression analysis with significant differences between groups determined (analysis of variance). RESULTS: A wear-in period was observed from 0 to 1 Mc. Wear rates were therefore calculated from 1 Mc. The wear rate for Group 1 was significantly less than Groups 2 to 4 through 10 Mc. From 1 to 5 Mc, the wear rate for Group 1 was significantly less than all groups, with Groups 2 to 4 not significantly different from each other. The wear rates for Groups 2 to 4 were seen to decrease after 5 Mc with only Group 3 significantly different than Group 1. The Group 1 wear rate was consistent throughout the test duration of 40 Mc. CONCLUSION: The experimental wear rates compare well with the reported wear rates of other material combinations used in nucleus replacement and total disc arthroplasty. Overall, wear rates were relatively low and consistent, suggesting long-term durability, a critical requirement of disc arthroplasty devices. PMID- 20581751 TI - Medical management of spinal tuberculosis: an experience from Pakistan. AB - STUDY DESIGN: A prospective study on spinal tuberculosis conducted at Fauji Foundation Hospital, Rawalpindi, Pakistan, with 1 year of follow-up. OBJECTIVE: The main aim was to diagnose spinal tuberculosis on clinical grounds and with simple noninvasive laboratory and radiology investigations and to treat the patients with antituberculosis drugs. SUMMARY OF BACKGROUND DATA: Spinal tuberculosis associated with any neuro deficit is usually treated by surgery. Medical treatment can reverse most of the neuro deficit. Surgery should not be the first choice of treatment. METHODS: Twenty-six patients with spinal tuberculosis were clinically diagnosed, were started on antituberculosis treatment, and were followed up for 12 months. RESULTS: Backache is the most common symptom. Thirty-eight percent of patients presented with neuro deficit in the form of paraplegia and quadriplegia. Erythrocyte sedimentation rate was high in 100% cases. Plain radiograph diagnosed the disease in 88.27% patients. Eighty five percent of cases completely improved on medical treatment without any surgical intervention. CONCLUSION: Uncomplicated spinal tuberculosis is a medical problem. The study shows that surgical intervention is not always necessary. PMID- 20581752 TI - Two recurrences of adjacent spondylodiscitis after initial surgical intervention with posterior stabilization, debridement, and reconstruction of the anterior column in a patient with spondylodiscitis: a case report. AB - STUDY DESIGN: Case report. SUMMARY OF BACKGROUND DATA: This report describes a patient who had 2 episodes of destructive spondylodiscitis occurring adjacent to levels at which surgery had previously been carried out due to an initial spondylodiscitis. A review of the literature did not reveal any equivalent cases. A comprehensive description of the management of this unusual course of spondylodiscitis is therefore presented here. METHODS: Initially, the patient was suffering from L1-L2 spondylodiscitis caused by previous staphylococcal sepsis. After ineffective conservative antibiotic treatment, surgery was carried out, with posterior instrumentation and fusion at T11-L4 and removal and replacement of the L1 and L2 vertebral bodies. RESULTS: After 2 months, the patient presented with paraparesis due to adjacent spondylodiscitis at T10-T11. The posterior instrumentation was therefore extended up to T9, and removal of the vertebral body of T11 was carried out. After 14 months, the patient was readmitted with pain and increased inflammatory parameters due to spondylodiscitis at T8/T9. Removal of the vertebral bodies was again carried out at T8 and T9, and posterior fusion up to T5 was performed. The patient received antibiotic treatment from 2 months before the first operation up to 3 months after surgery. CONCLUSION: Newly developing spondylodiscitis adjacent to a level at which a previous spondylodiscitis has been treated surgically is a rare condition, and aggressive treatment is necessary. PMID- 20581753 TI - Bilateral femoral artery ischemia detected by multimodality neuromonitoring during posterior scoliosis surgery: a case report. AB - STUDY DESIGN: Case report. OBJECTIVE: To report a case of a bilateral femoral artery ischemia detected by neuromonitoring during posterior scoliosis surgery and to review relevant literature regarding this rare complication. SUMMARY OF BACKGROUND DATA: Lower extremity ischemia is a potentially devastating risk of posterior spinal surgery. Ischemia can be a result of thrombotic occlusion or vascular compression during patient positioning. Multimodality neuromonitoring, increasingly used to prevent neurologic injury, can also detect hypoperfusion to the extremities. To date, there have been no reports of bilateral lower extremity ischemia detected by multimodality neuromonitoring during posterior spine surgery. METHODS: A 15-year-old boy with adolescent idiopathic scoliosis underwent posterior spinal fusion with instrumentation. Intraoperative changes in somatosensory-evoked potentials and motor-evoked potentials were noted 1 hour into the case, before instrumentation or the reduction maneuver. After trouble shooting methods did not localize a technical cause for the changes, the patient's lower extremities were noted to be hypoperfused and pulseless. RESULTS: The patients was repositioned and lower extremity perfused improved. Palpable distal pulses were detected. Neuromonitoring signals returned to baseline and the surgery completed. The patient had no postoperative neurologic or vascular deficits. CONCLUSION: Lower extremity ischemia secondary to prone positioning is a rare risk of posterior spinal surgery. This is the first case report of this potentially devastating, but preventable complication detected by multimodality neuromonitoring. PMID- 20581755 TI - Preservation of muscles attached to the C2 and C7 spinous processes rather than subaxial deep extensors reduces adverse effects after cervical laminoplasty. AB - STUDY DESIGN: Prospective study. OBJECTIVE: To examine whether preservation of subaxial deep extensor muscles plays any significant role in reducing axial neck pain and unfavorable radiologic changes after cervical laminoplasty in patients with cervical spondylotic myelopathy and to confirm the benefits of preserving muscles attached to the C2 and C7 spinous processes. SUMMARY OF BACKGROUND DATA: Axial neck pain and unfavorable radiologic changes after cervical laminoplasty have been reported to mostly result from detachment of cervical extensor muscles, particularly muscles attached to the C2 and C7 spinous processes. Other surgeons have reported that preservation of subaxial deep extensor muscles reduces these adverse effects after cervical laminoplasty. METHODS: Subjects comprised 36 patients with cervical spondylotic myelopathy who underwent C3-C6 open-door laminoplasty and were followed up for >24 months. Of these, 18 consecutive patients underwent our modified laminoplasty (muscles-preserved group) and the remaining 18 consecutive patients underwent the conventional procedure (muscles disrupted group). Both procedures preserved all muscles attached to the C2 and C7 spinous processes. Subaxial deep extensor muscles on the hinged side were also preserved in the muscles-preserved group. Radiologic and clinical data were prospectively collected. RESULTS: Both groups achieved equal neurologic improvement. Frequencies of axial neck pain showed no significant differences between groups. This value did not vary according to the side of preservation of subaxial deep extensor muscles or the side of muscle disruption. Postoperative loss of lordosis and range of motion of the cervical spine also demonstrated no significant difference between groups. CONCLUSION: These results indicate that preservation of subaxial deep extensor muscles plays no significant role in reducing axial neck pain and unfavorable radiologic changes after cervical laminoplasty, supporting the hypothesis that these adverse effects after laminoplasty largely result from detachment of muscles attached to the C2 and C7 spinous processes. PMID- 20581754 TI - Natural history of spinopelvic alignment differs from symptomatic deformity of the spine. AB - STUDY DESIGN: Cross-sectional study and systematic review of the literature. OBJECTIVE: Describe the natural history of spinopelvic alignment parameters and their behavior in patients with degenerative spinal deformity. SUMMARY OF BACKGROUND DATA: Normal stance and gait requires congruence between the spine sacrum and pelvis-lower extremities. This is determined by the pelvic incidence (PI), and 2 positional parameters, the pelvic tilt, and sacral slope (SS). The PI also affects lumbar lordosis (LL), a positional parameter. The final goal is to position the body's axis of gravity to minimize muscle activity and energy consumption. METHODS: Two study cohorts were recruited: 32 healthy teenagers (Risser IV-V) and 54 adult patients with symptomatic spinal deformity. Standing radiographs were used to measure spinopelvic alignment and positional parameters (SS, PI, sacral-femoral distance [SFD], C7-plumbline [C7P], LL, and thoracic kyphosis). Data from comparable groups of asymptomatic individuals were obtained from the literature. RESULTS: PI increases linearly with age (r2 = 0.8646) and is paralleled by increasing SFD (r2 = 0.8531) but not by SS. Patients with symptomatic deformity have higher SFD (42 +/- 13.6 mm vs. 63.6 +/- 21.6 mm; P < 0.001) and lower SS (42 degrees +/- 9.6 degrees vs. 30.7 degrees +/- 13.6 degrees; P < 0.001) but unchanged PI. The C7P also presents a linear increase throughout life (r2 = 0.8931), and is significantly increased in patients with symptomatic deformity (40 +/- 37 mm vs. 70.3 +/- 59.5 mm; P < 0.001). CONCLUSION: First, Gradual increase in PI is described throughout the lifespan that is paralleled by an increase in SFD, and is not by an increase in the SS. This represents a morphologic change of the pelvis. Second, Patients with symptomatic deformity of the spine present an increased C7P, thoracic hypokyphosis, reduced LL, and signs of pelvic retroversion (decreased LL and SS; increased SFD). PMID- 20581756 TI - Anterior cervical arthrodesis using a "stand alone" cylindrical titanium cage: prospective analysis of radiographic parameters. AB - STUDY DESIGN: Prospective, observational study. OBJECTIVE: To evaluate biomechanical changes associated with cervical arthrodesis using a cylindrical titanium cage. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion (ACDF) is the "gold standard" for treating cervical disc disease. In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages are used to achieve fusion. The cages should allow for restoration and maintenance of natural disc height, angulations, and displacements at the operated levels. METHODS: Fifty-four patients underwent standard ACDF using a "stand alone" cylindrical cage implant. Lateral radiographic views of the cervical spine were obtained before surgery, on the first day postoperatively, and at 12 months postoperatively. Disc height, vertebral alignment, angle of lordosis, and range of motion at operated levels were quantified prospectively by distortion compensated Roentgen analysis. RESULTS: At 12 months postoperatively, solid fusion was achieved but the cylindrical cage failed to preserve disc height, prevent kyphosis, and preserve natural intervertebral alignment. We observed significant cage subsidence and malalignment. CONCLUSION: We noticed several unfavorable outcomes when performing an analysis of radiographic parameters after ACDF using a cylindrical titanium cage. Thus, the use of a "stand alone" cylindrical cage in ACDF should be considered with caution. PMID- 20581757 TI - Minimal access versus open transforaminal lumbar interbody fusion: meta-analysis of fusion rates. AB - STUDY DESIGN: A quantitative meta-analysis was conducted on published studies reporting fusion rates after open or minimally invasive/mini-open transforaminal lumbar interbody fusion (TLIF) procedures for single or multilevel degenerative disease including stenosis with spondylolisthesis and degenerative disc disease. OBJECTIVES: The primary aim of this study was to establish benchmark fusion rates for open TLIF and minimally invasive TLIF (mTLIF) based on published studies. A secondary goal was to review complication rates for both approaches. SUMMARY OF BACKGROUND DATA: Lumbar fusion for the treatment of degenerative disease has evolved from a purely posterior noninstrumented approach to a combination of anterior and/or posterior surgery with instrumentation. The increasingly popular transforaminal approach has advanced to incorporate minimally invasive spinal techniques. There currently exist no controlled comparisons between open TLIF and mTLIF. METHODS: A Medline search was performed to identify studies reporting fusion rate on open TLIF or mTLIF with instrumentation. A database including patient demographic information, fusion rate, and complication rate was created. Fusion and complication rates were pooled according to whether TLIF was performed with open or minimally invasive technique. Publication bias was assessed with Egger's test, and adjustments were performed using Duval and Tweedie's Trim and Fill algorithm. RESULTS: Twenty-three articles were identified that fit inclusion criteria. In each of the 23 studies, TLIF was performed with pedicle fixation and fusion was evaluated using radiograph or computed tomography scan at minimum 6 month follow-up. Overall, the studies included 1028 patients, 46.8% of which were female. The mean age of all patients was 49.7 (range, 38-64.9), and mean follow up interval for assessment of fusion was 26.6 months (range, 6-46 months). The usage of recombinant bone morphologic protein was higher in the mTLIF group (50% vs. 12%). Mean fusion rate from 16 studies (716 patients) of open TLIF was 90.9%, whereas mean fusion rate from 8 studies (312 patients) of mTLIF was 94.8%. Complication rate was 12.6% and 7.5% for open and mTLIF, respectively. CONCLUSION: Fusion rates for both open and mTLIF are relatively high and in similar ranges. Complication rates are also similar, with a trend toward mTLIF having a lower rate. This analysis provides clear benchmarks for fusion rates in open and mTLIF procedures for spine surgeons. PMID- 20581758 TI - Bone morphogenetic protein binding peptide mechanism and enhancement of osteogenic protein-1 induced bone healing. AB - STUDY DESIGN: In vitro and in vivo evaluation of BBP interactions with BMP. OBJECTIVE: To explore bone morphogenetic protein-binding peptide (BBP)'s mechanism of action, investigate an extended repertoire for BBP applications, and evaluate the usefulness of BBP as a surgical adjuvant when used with recombinant human osteogenic protein-1 (rhOP-1). SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins (BMPs) are osteoinductive proteins that provide a potential alternative to autograft. Their utility is limited by cost, and potential dose-dependent risks, such as local inflammatory reactions and ectopic bone formation. BBP, a cyclized synthetic peptide, avidly binds recombinant human BMP-2(rhBMP-2) and has been shown to accelerate and enhance its osteogenic qualities. METHODS: BBP binding with 4 growth factors from the transforming growth factor -beta family were assessed using surface plasmon resonance. The in vivo retention of rhBMP-2 was quantified by comparing the percentage of retained [125I]-labeled rhBMP-2 in absorbable collagen sponge implants with or without BBP at 1, 3, and 7 days postimplantation. The adjunctive effect of BBP with rhOP-1 induced bone growth was evaluated by comparing time to fusion and fusion rates in a rodent posterolateral fusion model with 2 different doses of rhOP-1 with or without BBP. RESULTS: BBP bound all 4 growth factors with an intermediate affinity. The in vivo retention of rhBMP-2 alone ranged from about 40% on day 1 to about 30% on day 7, whereas, the retention of rhBMP-2 in the presence of BBP was about 85% on day 1 and about 55% on day 7. The addition of BBP to rhOP-1 resulted in significantly earlier and greater fusion rates than achieved with rhOP-1 alone. CONCLUSION: The mechanism of the BBP enhanced osteoinductive properties of BMPs involves the binding and retention of the growth factor, resulting in a prolonged exposure of BMP to the desired fusion site. The use of BBP in conjunction with BMPs may prove to provide satisfactory fusion outcomes, while reducing the costs and side effects associated with BMP use. PMID- 20581759 TI - Responsiveness of the Bournemouth questionnaire in determining minimal clinically important change in subgroups of low back pain patients. AB - STUDY DESIGN: Prospective single cohort. OBJECTIVE: To determine the ability of the Bournemouth Questionnaire (BQ) to distinguish between improved and nonimproved patients who present with either short (acute) or long (subacute/chronic) duration low back pain (LBP), and with either high or low baseline scores (severity). SUMMARY OF BACKGROUND DATA: Recent evidence suggests that the responsiveness of outcome measures used to determine clinical change is dependent on the chronicity and severity of the condition. METHODS: Data from 437 back patients undergoing chiropractic treatment were used for analysis. Patients completed the BQ before treatment and 4 weeks later. Patients also completed the Patient Global Impression of Change scale at follow-up. Responsiveness was determined by calculating Standardized Response Means (SRM) and by the area under the receiver operator curve (ROC) with best cut-point analysis. The minimal clinically important change (MCIC) was calculated by the change score with the best balanced sensitivity and specificity. RESULTS: The responsiveness of the BQ at 4 weeks was dependent on both duration and severity of the condition. As expected, the responsiveness of the total BQ was greater in improved compared to nonimproved patients in the acute (SRM [95% confidence interval], 1.9 [1.7-2.0] and 1.2 [0.9-1.5], respectively), as well as in the subacute/chronic group (SRM, 1.7 [1.5-1.8] and 0.5 [0.3-0.7]), respectively. For the psychological domains, SRMs in the acute patients failed to distinguish improved from nonimproved patients (SRM [95% confidence interval], 1.3 [1.1-1.4] and 0.9 [0.5-1.2] for anxiety, and 0.9 [0.8-1.0] and 0.8 [0.5-1.2] for depression). In acute and subacute/chronic patients, the MCIC for the total BQ was 26 and 18 points, respectively. In patients with lower and higher BQ scores at baseline, the MCIC was 10 and 31 points, respectively. CONCLUSION: The BQ can distinguish between improved and nonimproved LBP patients but the amount of change needed to achieve this is lower in more chronic patients and in individuals with less severe presentation at baseline. PMID- 20581760 TI - Complication rates of three common spine procedures and rates of thromboembolism following spine surgery based on 108,419 procedures: a report from the Scoliosis Research Society Morbidity and Mortality Committee. AB - STUDY DESIGN: Retrospective review of a prospectively collected database. OBJECTIVE: The Scoliosis Research Society (SRS) collects morbidity and mortality (M and M) data from its members. Our objectives were to assess complication rates for 3 common spine procedures, compare these results with prior literature as a means of validating the database, and to assess rates of pulmonary embolism (PE) and deep venous thrombosis (DVT) in all cases reported to the SRS over 4 years. SUMMARY OF BACKGROUND DATA: Few modern series document complication rates of spinal surgery as routinely practiced across academic and community settings. Those available are typically based on relatively low numbers of procedures or confined to single-surgeon experiences. METHODS: The SRS M and M database was queried for lumbar microdiscectomy (LD), anterior cervical discectomy and fusion (ACDF), and lumbar stenosis decompression (LSD) cases from 2004 to 2007. Revisions were excluded. The database was also queried for occurrence of clinically evident PE and DVT in all cases from 2004 to 2007. RESULTS: A total of 9692 LDs, 6735 ACDFs, and 10,329 LSDs were identified, with overall complication rates of 3.6%, 2.4%, and 7.0%, respectively. These rates are comparable to previously published smaller series. For assessment of PE and DVT, 108,419 cases were identified and rates were calculated per 1000 cases based on diagnosis, age group, and implant use. Overall rates of PE, death due to PE, and DVT were 1.38, 0.34, and 1.18, respectively. Among 82,082 adults, the rate of PE ranged from 0.47 for LD to 12.4 for metastatic tumor. Similar variations were noted for DVT and deaths due to PE. CONCLUSION: Overall major complication rates for LD, ACDF, and LSD based on the SRS M and M database are comparable to those in previously reported smaller series, supporting the validity of this database for study of other less common spinal disorders. In addition, our data provide general benchmarks of clinically evident PE and DVT rates as a basis for ongoing efforts to improve care. PMID- 20581761 TI - The cervical flexion-relaxation ratio: reproducibility and comparison between chronic neck pain patients and controls. AB - STUDY DESIGN: Reliability study. OBJECTIVE: To determine the reproducibility of the cervical flexion-relaxation ratio (FRR) measured 4 weeks apart in a group of chronic neck pain patients and healthy control group and to compare the FRR between the 2 groups. SUMMARY OF BACKGROUND DATA: The cervical FRR measures the ability of the neck extensor muscles to relax during forward flexion, similar to the lumbar FRR. Its reliability and ability to discriminate neck pain patients from controls has not been investigated. METHODS: Fourteen participants with chronic neck pain and a control group of 14 individuals with no neck pain were recruited via advertisement and word of mouth. The cervical FRR was determined at baseline and 4 weeks later using standardized electromyographic data collection and analysis procedures. RESULTS: The mean FRR value for the combined left and right side data for the neck pain groups was 1.93 +/- 0.8, and 1.73 +/- 0.61 at 4 week follow-up. The intraclass correlation coefficient (ICC) was 0.83 (95% CI = 0.67-0.92). Three participants in the control group developed neck pain in the 4 weeks and their data were not included in the reliability calculation. For the control group, the combined (left and right side) mean FRR value was 4.09 +/- 1.58 at baseline and 4.27 +/- 1.71 on retest 4 weeks later. The ICC (intraclass r) was 0.89 (95% confidence interval = 0.76-0.95). The overall ICC for the combined groups was 0.92 (95% confidence interval = 0.86-0.95). An independent 2 group t test revealed a significant difference in the baseline FRR data between the control group and the neck pain group (P < 0.001). CONCLUSION: The cervical extensor muscles exhibit a consistent flexion-relaxation phenomenon in healthy control subjects and the measurement is highly reproducible when measured 4 weeks apart in both controls and chronic neck pain patients. The FRR in neck pain patients is significantly higher than in control subjects suggesting that this measure may be a useful marker of altered neuromuscular function. PMID- 20581762 TI - Comparison of magnetic resonance imaging and computed tomogram-myelography for evaluation of cross sections of cervical spinal morphology. AB - STUDY DESIGN: Comparison of magnetic resonance imaging (MRI) and computed tomography-myelography (CTM) for cervical intracanalar dimensions. OBJECTIVE: To compare the capability and reproducibility of MRI and CTM in measuring the cross sectional morphology of intracanalar lesions of the cervical spine. SUMMARY OF BACKGROUND DATA: The relative advantages and disadvantages of MRI and CTM in measuring cervical intracanalar dimensions are poorly understood. METHODS: MRI and CTM were used to measure cervical disc levels in 45 subjects with various cervical spinal diseases. Measurements included dural area, dural anteroposterior (A-P) diameter, dural right-left (RL) diameter, cord area, cord anteroposterior (A-P) diameter, cord right-left (RL) diameter and cerebrospinal fluid (CSF) space (anterior and posterior). Each section was graded by 2 orthopedic surgeons for degree of stenosis (Grades, 0-3), and the intra- and interobserver reproducibility of these measurements (intraclass correlation coefficients: ICC) was assessed. RESULTS: In both CTM and MRI, intra- and interobserver reproducibility (ICC) ranged from 0.702 to 0.989, suggesting that both imaging methods are reproducible. Importantly, CTM measurements of dural area, dural A-P diameter, dural RL diameter, and CSF space (anterior and posterior) were slightly, but significantly (P < 0.001), larger than MRI measurements. In contrast, MRI measurements of cord area, cord A-P diameter, and cord RL diameter were slightly, but significantly (P < 0.001), larger than CTM measurements. Degree of stenosis was significantly more severe in MRI than in CTM. CONCLUSION: Both CTM and MRI provided reproducible measurements of cervical intracanalar dimensions. Measurements of dura were slightly larger in CTM, whereas measurements of spinal cord were slightly larger in MRI, making stenosis more severe in MRI than in CTM. The clinical relevance of these slight differences requires further examination. PMID- 20581763 TI - Surgical management of two- versus three-column injuries of the cervicothoracic junction: biomechanical comparison of translaminar screw and pedicle screw fixation using a cadaveric model. AB - STUDY DESIGN: An in vitro cadaveric biomechanical study. OBJECTIVE: To determine the stability of translaminar screws compared to pedicle screws at T1-T2 for constructs bridging the cervicothoracic junction. SUMMARY OF BACKGROUND DATA: Instrumented fixation of the cervicothoracic junction is challenging both biomechanically, due to the transition from the mobile cervical to the rigid thoracic spine, and technically, due to the anatomic constraints of the T1-T2 pedicles. For these reasons, an alternate fixation technique at T1-T2 that combines ease of screw insertion and a favorable safety profile with biomechanical stability would be clinically beneficial. METHODS: A 6-degree of freedom spine simulator was used to test multidirectional flexibility in 8 human cadaveric specimens. Flexion, extension, lateral bending, and axial rotation were tested in the intact condition, followed by destabilization via a simulated 2 column injury at C7-T1. Specimens were reconstructed using C5-C6 lateral mass screws and either translaminar or pedicle screws placed at T1, followed by caudal extension to T2. A 3-column injury at C7-T1 was then performed and specimens were tested using a posterior only approach with either translaminar or pedicle screws placed at T1 and T1-T2. Finally, anterior fixation at C7-T1 was added and multidirectional flexibility testing performed as previously described. RESULTS: Following a 2-column injury at C7-T1, there were no significant differences in segmental flexibility at C7-T1 between translaminar and pedicle screw fixation when placed at T1-T2 (P>0.05). For a 3-column injury treated posteriorly, translaminar screws at T1-T2 provided increased flexibility compared to pedicle screws in flexion/extension (P<0.05). There were no differences in segmental flexibility at C7-T1 between the 2 techniques following the addition of anterior fixation (P>0.05). CONCLUSION: Translaminar screws in the upper thoracic spine offer similar stability to pedicle screw fixation for constructs bridging the cervicothoracic junction. Small differences in range of motion must be weighed clinically against the potential benefits of translaminar screw insertion at T1 T2. PMID- 20581764 TI - Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement. AB - STUDY DESIGN: Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. OBJECTIVE: This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. SUMMARY OF BACKGROUND DATA: HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. METHODS: A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. RESULTS: Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. CONCLUSION: Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study. PMID- 20581765 TI - An international survey of cytomegalovirus management practices in lung transplantation. AB - BACKGROUND: Cytomegalovirus (CMV) is an important infection in lung transplant recipients. Center-to-center variation in preventive and treatment strategies is unknown. METHODS: An electronic survey was sent to 102 lung transplant programs registered with the International Society of Heart and Lung Transplantation and United Network for Organ Sharing. RESULTS: Fifty-nine (58%) programs responded to the survey. For CMV prevention (D+/R-), 56 of the 59 (94.9%) programs used prophylaxis and two (3.4%) of them used preemptive therapy. For R+ patients, 86.4% used prophylaxis and 13.6% used preemptive strategy. Duration of prophylaxis was extremely variable ranging from 3 months to indefinite. Adjunctive prophylactic strategies included routine viral monitoring (51% D+/R-; 44% R+) and CMV immunoglobulin (32% D+/R-; 14% R+). The medication used for prophylaxis was valganciclovir with approximately half starting with intravenous ganciclovir. 9 of the 59 (15.2%) centers reported using specific CMV prophylaxis in D-/R- patients. Methods for viral monitoring included peripheral blood polymerase chain reaction, antigenemia, bronchoalveolar lavage viral culture, and bronchoalveolar lavage polymerase chain reaction. For treatment of CMV viremia, valganciclovir or intravenous ganciclovir were used. A total of 47.5% of centers routinely decreased immunosuppression at the time of viremia. Secondary antiviral prophylaxis was used routinely by 36 of the 59 (61%) centers. CONCLUSIONS: Although prophylaxis is the most commonly used preventive strategy, significant variation exists in the way it is implemented. Specifically, duration of prophylaxis is extremely variable. Uniform international guidelines would be of value in this population. PMID- 20581766 TI - Prediction of graft dysfunction based on extended criteria donors in the model for end-stage liver disease score era. AB - BACKGROUND: To explain the influence of recipient status combined with the accumulation of extended criteria donor (ECD) variables on the appearance of severe ischemia-reperfusion injury and graft survival in a model for end-stage liver disease (MELD)-based system, we analyzed our most recent consecutive liver transplantations (LTs), dividing them into two periods: 400 LTs (1992-2002; pre MELD era) and 275 LTs (2002-2007; post-MELD era). METHODS: Primary dysfunction (PD) was defined as primary graft failure that required emergency retransplantation or as initial poor function. Donor variables were included in a regression model to assess the probability of PD. RESULTS: Donor age, macrovesicular steatosis more than 30%, and cold ischemia time were associated with allograft dysfunction. Mean probability of PD was 14.8%, 19.2%, 27.5%, and 37.4% for ECD 0, 1, 2, and more than or equal to 3, respectively (P=0.003). Distribution of no-mild, moderate, and severe ischemia-reperfusion injuries among MELD categories was 72.53%, 24.17%, and 3.30% (MELD group=12-19); 56.52%, 36.96%, and 6.5% (MELD group=20-28); and 23.91%, 54.35%, and 21.74% (MELD group >or=29), respectively (P=0.043). The development of PD according to ECD variables was 18.8%, 18.1%, 28.0%, and 35.3% for ECD 0, 1, 2, and more than or equal to 3, respectively (P=0.047). These variables were independent predictors of PD (Cox proportional regression model): ECD 2 (relative risk [RR]=1.59; 95% confidence interval [CI]=1.25-1.62), ECD 3 (RR=2.74; 95% CI=2.38-3.13), MELD 21 to 30 (RR=1.89; 95% CI=1.32-2.06), and MELD more than or equal to 30 (RR=3.38; 95% CI=2.43-3.86). Graft survival decreased, whereas MELD and the number of ECD variables increased. CONCLUSION: The combination of three or more ECD variables and an MELD more than or equal to 29 is the worst scenario for graft success after LT. PMID- 20581767 TI - Aspergillus fumigatus synergistically enhances mite-induced allergic airway inflammation. AB - BACKGROUND: Infection is an important trigger of exacerbation of bronchial asthma. The fact that Aspergillus fumigatus (Af) causes a distinct clinical syndrome, allergic bronchopulmonary aspergillosis (ABPA), suggests unique immunological properties in allergic asthma. The present study aimed to determine how Af enhances preexisting allergic airway inflammation and colonizes the airway in asthma. MATERIAL/METHODS: Six groups of BALB/c mice were prepared: Control; live or dead Af-infected (Live Af or Dead Af); Dermatophagoides farinae (Df) allergen-sensitized (Df); and Df-sensitized plus live or dead Af-infected (Df live Af or Df-dead Af). Pulmonary pathology, cytokine profiles and mucous production in the airway were evaluated in these groups. RESULTS: Af infection significantly enhanced Df allergen-induced eosinophilic inflammation via enhancement of Th2-like response. Live, but not dead, Af significantly exacerbated neutrophilic inflammation. Induction of IL-13 and Muc5ac proteins by Df allergen sensitization was significantly enhanced by both live and dead Af infection, resulting in mucous hypersecretion. CONCLUSIONS: Collectively, the present study showed that mite allergen sensitization concomitant with Af infection enhanced Th2-dominant immune response in the airway, which induced mucous hypersecretion and potentially permitted further colonization by Af spores. It is likely that Af enhances allergic airway inflammation as an allergen, while it enhances neutrophilic airway inflammation as a pathogen. Future studies on pharmacological intervention in the present murine model utilizing glucocorticoid, and anti-fungal drugs are thus promising. PMID- 20581768 TI - Diagnostic value of estrogen receptors in thyroid lesions. AB - BACKGROUND: The objective of this study was to evaluate the presence of estrogen receptors (ER) alpha and beta in various thyroid lesions and to assess the practicality of this test. MATERIAL/METHODS: Immunohistochemical stains were performed for both ERalpha and ERbeta, for evaluation of immunoreactivity in 296 thyroid tissue samples that consisted of 150 goiters, 90 papillary carcinomas, 19 follicular adenomas, 15 Hurtle cell adenomas, 6 Hashimoto thyroiditis, 5 anaplastic carcinomas, 4 medullary carcinomas, 4 follicular carcinomas, 2 Hurtle cell carcinomas, and 1 squamous cell carcinoma of the thyroid. Three variables were evaluated in each sample: The intensity of the staining both nuclear (1) and cytoplasmic (2), and the spread of the stain over the sample (3). RESULTS: None of the histologic samples showed immunoreactivity for ERalpha. Positive immunoreactivity results for ERbeta were found in tissue samples from all of the different groups of diagnoses, both benign and malignant lesions as well as in normal thyroid tissue. No significant difference was found between the various thyroid lesions. CONCLUSIONS: The study shows that ERbeta is the only ER detectable in thyroid tissue. However, ERbeta expression has no significant specifications for differentiation between benign and malignant lesions of the thyroid. ERalpha is undetectable in the thyroid. Further investigations are necessary mainly in the laboratory immunohistochemical workup. PMID- 20581769 TI - Differential nutritional, endocrine, and cardiovascular effects in obesity-prone and obesity-resistant rats fed standard and hypercaloric diets. AB - BACKGROUND: This study tested whether rats with obesity induced by a hypercaloric diet (HD) present higher nutritional, endocrine, and cardiovascular disturbances compared with counterparts with obesity induced by overfeeding of a standard diet. An additional objective was to compare the isolated influence of HD on these parameters in lean and obese rats. MATERIAL/METHODS: Twenty Wistar-Kyoto rats were distributed into four groups: CD-lean, CD-obese, HD-lean, and HD-obese. CD (control diet) and HD groups received commercial standard chow and HD, respectively, for 20 weeks. The lean and obese groups included obesity-resistant and obesity-prone animals, respectively. Nutritional and metabolic evaluation involved measurement of calorie intake, dietary efficiency, body weight, adiposity, glycemia, triacylglycerol, insulin, and leptin. Cardiovascular evaluation included systolic blood pressure measurement, echocardiography, and analyses of myocardial morphology and myosin heavy-chain composition. RESULTS: In both diets, obesity was characterized by increased adiposity, hyperleptinemia, hypertriacylglycerolemia, hyperinsulinemia, and cardiomyocyte nuclear hypertrophy. HD promoted hyperleptinemia and cardiac remodeling, characterized by nuclear and ventricular hypertrophy, as well as improved systolic performance in both the obesity-prone and obesity-resistant biotypes. In contrast to HD-lean, HD obese rats presented more accentuated endocrine responses, including hyperglycemia, lower glycemic tolerance, and hyperleptinemia as well as interstitial fibrosis compared with the CD-obese animals. CONCLUSIONS: This study confirmed the primary hypothesis that rats with HD-induced obesity present more accentuated nutritional and endocrine disturbances compared with their counterparts with obesity resulting from overfeeding. In addition, dietary effects were more important between the obese groups, supporting evidence of an interaction between diet and biotype. PMID- 20581770 TI - Organ-related cigarette smoke-induced oxidative stress is strain-dependent. AB - BACKGROUND: Cigarette smoke (CS) is associated with oxidative stress in several organs because it contains high concentrations of free radicals and reactive oxygen species. Experimental models, using different strains, provide important insights into the genetic basis of diseases. This study sought to identify, in different mouse strains, the organ that is most-susceptible to CS-induced oxidative stress to obtain an optimized experimental animal model of oxidative injury induced by CS. MATERIAL/METHODS: Male Swiss, DBA/2, C3H, BALB/c, and C57BL/6 mice were exposed to CS 3 times a day (4 cigarettes per session) for 60 consecutive days. Control groups from the same strains were sham-treated. Protein content, malondialdehyde level, myeloperoxidase activity, and nitrite level were assayed in lung, liver, kidney, and brain from all strains. Catalase and glutathione peroxidase activities were measured. Analyses of data were done by using a 1-way ANOVA with Bonferroni's post-test (P<.05). RESULTS: Cigarette smoke exposure resulted in distinct, organ-specific responses among strains. The survival rate of DBA/2 mice was lowest. BALB/c and C57BL/6 strains were more susceptible to oxidative damage in the lung and liver. C3H and C57BL/6 mice were more-susceptible to oxidative damage in the brain. No renal oxidative damage was seen. CONCLUSIONS: Mouse strains and individual organs display a range of susceptibilities to CS-induced oxidative stress. BALB/c and C57BL/6 strains appear to be the best choices as experimental models for studying CS effects on liver and lung, and C3H and C57BL/6 strains for CS-effects on the brain. PMID- 20581771 TI - Adrenaline inhibits the immunological activation of human basophils at pharmacological and ultra-low doses. AB - BACKGROUND: Adrenaline is known to inhibit the immunological activation of human basophils. The same effect can be obtained with ultra-low doses of histamine. MATERIAL/METHODS: The present investigation was undertaken to verify the effects of ultra-low doses of adrenaline on the immunological activation of human basophils. For this purpose, purified human basophils were isolated from the blood of atopic donors and the response of the basophils to anti-IgE antiserum was evaluated by measuring the release of histamine and the expressions of the activation markers CD63 and CD203c on the basophil surface. RESULTS: The antigenic activation of basophils was significantly decreased by adrenaline at both pharmacological and ultra-low doses. The inhibiting effects of adrenaline were reversed by the beta blocker propranolol at either dose level. CONCLUSIONS: Although seemingly unexplainable by the currently accepted pharmacological principles, this phenomenon, already reported for histamine, deserves further investigation. PMID- 20581772 TI - High sensitivity C-reactive protein, NT-proBNP and hemodynamic left ventricular function in acute coronary syndrome without ST segment elevation - a preliminary report. AB - BACKGROUND: Prognostic factors in acute coronary syndromes have been the subject of interest in cardiology over the last few years. Our study aimed to compare humoral marker concentration shifts (hsCRP, Nt-proBNP) and hemodynamic left ventricular systolic function index changes, determined by means of echocardiography in the first hours of acute coronary syndromes (ACS). MATERIAL/METHODS: The study comprised 33 patients with ACS without ST segment elevation. Group I consisted of 18 patients (11 men, 7 women aged from 48 to 77, mean age 67+/-35 years) with unstable angina pectoris (uAP). Group II consisted of 15 patients (10 men, 5 women aged from 51 to 80, mean age 70+/-11.9 years) with myocardial infarction without ST segment elevation (NSTEMI). In all patients, Nt-proBNP and hsCRP blood concentrations were determined between the 6th and 12th hours after admission to the intensive coronary care unit. On the 2nd-3rd day, after coronary stabilization, routine echocardiography was performed in each patient to assess left ventricular function. RESULTS: A positive correlation between hsCRP and Nt-proBNP in uAP was observed in group I. In group II, in patients with NSTEMI no such correlation was observed. There was also no correlation in either study group between humoral (hsCRP and Nt-proBNP) and hemodynamic parameters. CONCLUSIONS: The complex evaluation of the post-ACS prognosis should be multifaceted. It should contain hemodynamic assessment of the left ventricle by means of echocardiography as well as humoral coronary risk markers. PMID- 20581773 TI - Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients. AB - BACKGROUND: S100B is a prominent cell damage marker which can lead to sustained pro-inflammatory signaling. The aim was to investigate cross-sectional associations of steady-state S100B concentrations, particularly with C-reactive protein (CRP), in renal transplant recipients (RTRs) and also to investigate prospectively whether S100B would predict graft failure or mortality. MATERIAL/METHODS: Outpatient RTRs with a graft functioning for >1 year were eligible for participation in this study. S100B was determined at baseline from serum. Mortality and the occurrence of graft failure were recorded until September 2007. Multivariable linear regression analyses were performed to identify potential determinants of S100B. Multivariable Cox regression analyses were performed to investigate S100B as a potential predictor of mortality or graft failure. RESULTS: Five hundred eighty-one RTRs participated in the study. The median S100B concentration was 0.19 (0.14-0.25) microg/l. Recipient age (beta=0.009, p=0.02), body mass index (BMI) (beta=0.021, p<0.001), and creatinine clearance (beta=-015, p<0.001) were independently associated with S100B. During follow-up, 95 RTRs (16.4%) died and 41 (7.1%) developed graft failure. S100B levels did not predict mortality or graft failure. CONCLUSIONS: BMI, creatinine clearance, and age are determinants of steady-state serum S100B concentrations in renal transplant recipients. The association of BMI with S100B suggests that S100B might be a new adipokine. PMID- 20581774 TI - Comparative study on skin dose measurement using MOSFET and TLD for pediatric patients with acute lymphatic leukemia. AB - BACKGROUND: The object of this study was to compare the difference of skin dose measured in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using metal oxide semiconductor field-effect transistors (mobile MOSFET dose verification system (TN-RD-70-W) and thermoluminescent dosimeters (TLD-100 chips, Harshaw/ Bicron, OH, USA). Because TLD has been the most-commonly used technique in the skin dose measurement of TBI, the aim of the present study is to prove the benefit of using the mobile MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements during the total body irradiation (TBI) over thermoluminescent dosimeters (TLD). MATERIAL/METHODS: The measurements involved 10 pediatric patients ages between 3 and 14 years. Thermoluminescent dosimeters and MOSFET dosimetry were performed at 9 different anatomic sites on each patient. RESULTS: The present results show there is a variation between skin dose measured with MOSFET and TLD in all patients, and for every anatomic site selected, there is no significant difference in the dose delivered using MOSFET as compared to the prescribed dose. However, there is a significant difference for every anatomic site using TLD compared with either the prescribed dose or MOSFET. The results indicate that the dosimeter measurements using the MOSFET gave precise measurements of prescribed dose. However, TLD measurement showed significant increased skin dose of cGy as compared to either prescribed dose or MOSFET group. CONCLUSIONS: MOSFET dosimeters provide superior dose accuracy for skin dose measurement in TBI as compared with TLD. PMID- 20581775 TI - Locus of control, self-efficacy and attribution tendencies in obese patients - implications for primary care consultations. AB - BACKGROUND: To examine health- related locus of control, self- efficacy and attribution tendencies in obese patients and to discuss their impact on primary care consultations. MATERIAL/METHODS: 123 patients, showing a BMI >25 kg/m(2) and following a health Check up, rated questionnaires regarding health-related locus of control, self-efficacy and attribution tendencies concerning obesity. Physical health parameters like BMI, level of cholesterol, blood pressure and existing cardiovascular co morbidities were assessed by GPs. Statistical analysis were conducted using SPSSv16.0. RESULTS: Patients scored comparable to a norm- population on self- efficacy and the three dimensions of health related locus of control. Physical health parameters did not explain variance. Patients named mainly behavioral causes for their overweight; those with a BMI >30 kg/m(2) tend to attribute their bodyweight to genetically origins. CONCLUSIONS: In order to conduct individual tailored consultancies it is necessary to explore the individual beliefs and attitudes of patients of concern. It is suggested that locus of control and self- efficacy are obligatory issues to discuss in preventive encounters with these patients. GPs should be trained in techniques like motivational interviewing in order to encourage patients to take responsibility for their health and thus increase treatment outcome. PMID- 20581776 TI - A comparative study of the antiemetic efficacy of dexamethasone, ondansetron, and metoclopramide in patients undergoing gynecological surgery. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) are some of the most-common and undesirable adverse effects after surgery performed under general anesthesia. We investigated the prophylactic value of dexamethasone as an alternate to ondansetron or metoclopramide to prevent PONV after gynecologic surgery. MATERIAL/METHODS: One hundred sixty ASA I-II patients scheduled for elective gynecologic surgery were enrolled. Before induction of anesthesia, patients were randomly allocated to receive intravenously dexamethasone (8 mg) in group D, ondansetron (4 mg) in group O, metoclopramide (10 mg) in group M, and saline (2 mL) in group P. Total incidence of nausea and vomiting, rescue antiemetic requirement, pain scores, and any adverse effects were recorded at 3 observational periods (0-2 hours, 2-12 hours, and 12-24 hours). RESULTS: Total rates of PON, POV, and PONV were significantly higher in group P at 0-2 hours and 2-12 hours compared with group D, O, and M (P<.05). There was no difference in PON, POV, and PONV among D, O, and M groups. None of the groups differed in PONV in the subsequent 12-24 hours. Number of patients requiring rescue antiemetic was significantly higher in group P than the other groups at 0-2 hours (10%, 10%, 15%, and 45% in group D, O, M, and P) (P<.05). CONCLUSIONS: Prophylactic IV dexamethasone 8 mg significantly reduces the incidence of PONV in gynecologic surgery. At this dosage, dexamethasone is as effective as ondansetron 4 mg and metoclopramide 10 mg, and is more-effective than placebo. PMID- 20581777 TI - The behaviour of bone mineral density and bone metabolism index in young and menopausal women with the consideration of body mass index. AB - BACKGROUND: The bone fractures in patients with osteopeny have broaden the risk factors by body mass index (BMI) and bone metabolism assessment defined with bone scintigraphy. The aim of the study was to evaluate the behavior of bone mineral density (BMD) and bone metabolism index (IBM) in both young women and those more than 50 years old, as associated with BMI. MATERIAL/METHODS: BMD and IBM were assessed in young women (group 1; n=66) and those after 50 (group II; n=67) with the allowance for BMI (< or =25 kg/cm(2) and >25 kg/cm(2)). Detailed densitometric and radioisotopic examinations were performed in all patients. The results of BMI, IBM and BMD were compared. RESULTS: In women with BMI >25, IBM was insignificantly lower than in women with BMI <25, independent of age (p>0.05). Comparing with the women with normal BMI, there was a slight increase of femoral bone neck and the whole skeleton BMD, thus IBM was insignificantly lower (p>0.05). A powerful positive correlation was observed between IBM and BMD of femoral bone neck and the whole skeleton. With BMI <25, there was a weak positive correlation of BMI and IBM. In young women with BMI >25 there was a powerful positive correlation of BMD and IBM. CONCLUSIONS: Independently of BMI, together with age increase, BMD was lower, yet, the dependency between BMI and BMD was increasing. We showed a strong statistical dependency between BMD and IBM. PMID- 20581778 TI - Thrombomodulin and antibeta2-glycoprotein I in stroke in children. AB - BACKGROUND: A quantitative systematic review recently discussed the role of thrombomodulin (Thm) and antibeta2-glycoprotein I (beta2-GPI) in cerebral strokes in adults. Little is known about the problem in children. The aim of the study was to see if there is a difference in the values of Thm and beta2-GPI in children with ischemic stroke. MATERIAL/METHODS: Seventy patients were included, comprising 40 children who had had ischemic stroke of unknown etiology hospitalized from January 1995 to December 2005 at the Department of Developmental Neurology, Chair of Neurology Medical University of Gdansk, and 30 healthy volunteers (no autoimmunologic disease or headache in interview). The concentrations of thrombomodulin (Thm) and antibeta2-glycoprotein I (beta2-GPI) in A, M, and G immunoglobulins were determined according to an immunoenzyme method (ELISA). RESULTS: None of the investigated subjects had elevated levels of beta2-GPI. The patients with stroke had significantly higher Thm values than the healthy group. CONCLUSIONS: This finding of elevated levels of thrombomodulin in cases of pediatric cerebral stroke could help in measuring the extent or duration of parenchymal brain injury, or even perhaps response to future therapeutic maneuvers. All these implications may aid not only in the diagnosis and management of acute ischemic stroke, but encourage prophylactic action to prevent probable stroke relapse. PMID- 20581779 TI - Screening protocols for the prevention of occupational noise-induced hearing loss: the role of conventional and extended high frequency audiometry may vary according to the years of employment. AB - BACKGROUND: Although occupational noise-induced hearing loss (NIHL) has become a major problem in industrialized societies, there is a notable lack of effective screening protocols to ensure its early diagnosis. The aim of this study was to detect a potential role of extended high frequency (EHF) audiometry in industrial hearing screening protocols. MATERIAL/METHODS: The population consisted of 151 persons, working for 8 hours daily in a noisy environment (90-110 dBA). The changes of hearing thresholds in industrial workers were analyzed, not only with respect to their age, as has been presented by previous studies, but also with respect to the duration of their previous employment. RESULTS: During the first 10 years of employment, the frequencies 12500, 14000 and 16000Hz were the only ones significantly affected. For the second decade of employment, thresholds were significantly elevated only at 2000 and 4000Hz. After exceeding 20 years of employment, the affected frequencies were 250, 500 and 1000Hz. The effects of age on hearing acuity were significant at all frequencies for the first 2 groups. CONCLUSIONS: EHF audiometry seems able to identify the first signs of NIHL, much earlier than conventional audiometry, and therefore may need to be implemented in the screening examinations especially of workers with less than 1 decade of employment. Hearing screening protocols could become more efficient by adjusting their frequency ranges according to the frequencies "at risk", which correspond to the duration of the workers' previous employment. PMID- 20581780 TI - Reactive lymphoid hyperplasia of the liver associated with primary biliary cirrhosis. AB - BACKGROUND: Although reactive lymphoid hyperplasia (RLH) can be found in various organs, including the gastrointestinal tract, orbit, lung, and skin, its occurrence in the liver is rare. CASE REPORT: We report the case of a 47-year-old RLH woman who was identified with RLH of the liver during clinical follow- up of primary biliary cirrhosis. The mass, found incidentally during a medical examination, appeared on ultrasonogram as a hypoechoic mass in the 7th segment of the liver. Further analyses using composed tomography, magnetic resonance imaging, and angiography suggested malignancy, and we performed lateral segmentectomy of the liver. Histologically, the tumor was composed of lymphoid follicles with germinal centers that expressed kappa and lambda light-chain B cell markers at equal frequency, and no IgH gene rearrangements were detected in Southern blots. Based on these results, we identified the lesion as RLH. CONCLUSIONS: We suggest that this diagnosis be taken into consideration in other cases involving a space-occupying liver mass associated with autoimmune disease. PMID- 20581781 TI - Proximal extension of backwash ileitis in ulcerative-colitis - associated colon cancer. AB - BACKGROUND: Extension of the inflammatory process into the terminal ileum in ulcerative colitis is termed backwash ileitis. Ulcerative colitis patients with pancolitis and backwash ileitis may be at increased risk of colorectal carcinoma. A case of ulcerative colitis-associated cancer with backwash ileitis, which extended proximally over time, is described. CASE REPORT: A 67-year-old man was diagnosed with pancolitis; despite prednisolone and mesalazine treatment, he showed no improvement. Although initial endoscopic examination showed no abnormalities in the terminal ileum, a repeat colonoscopy 4 months later revealed erythema, absence of the vascular pattern, mucosal friability, and erosions within 30 cm of the terminal ileum in a continuous fashion from the cecum, and a flat, elevated lesion was found in the transverse colon. On histopathologic examination, the patient had nonspecific, active, chronic inflammation of the ileal mucosa, consistent with backwash ileitis, and colonic adenocarcinoma. Despite additional treatment with leukocytapheresis, the backwash ileitis progressed, with increased severity of mucosal inflammation and extensive erosions, 20 cm proximal to the primarily affected site of the ileum on repeat colonoscopy 2 months later. The patient underwent a proctocolectomy and excision of the terminal ileum with an ileostomy. CONCLUSIONS: Histopathology of the surgical specimen revealed marked backwash ileitis and submucosal, well differentiated adenocarcinoma. The patient has remained well for 5 years after surgery. PMID- 20581782 TI - Cerebral air embolism after arthrography of the ankle. AB - BACKGROUND: The accidental migration of air from the venous circulation into the systemic arterial circulation is called paradoxical air embolism. This is a potential disastrous complication after diagnostic and surgical procedures. Arthrography has been a useful technique in joint imaging for the past decades. Paradoxical cerebral air embolism is a very rare complication, only a few cases have been reported after arthrography of the hip in children. Here, we describe a patient with progressive encephalopathy after computer tomography (CT) arthrography of the ankle. CASE REPORT: We describe a 64-year-old male who underwent CT-arthrography of the left ankle, after the intra-articular injection of 20 ml of air he experienced progressive neurologic and hemodynamic deterioration. A brain CT showed a small amount of air in a right frontal sulcus. Hyperbaric oxygen therapy (HBO) was initiated after a delay of 16 hours and resulted in a complete recovery. A transesophageal echocardiography confirmed the presence of a right-left shunt. CONCLUSIONS: This case of paradoxical air embolism with severe neurological manifestations after arthrography of the ankle, emphasizes that air embolism should be considered in all patients with neurologic and/or hemodynamic deterioration after the injection of intra articular air. Furthermore a delay of more then 6 hours is no reason to withhold HBO in these patients. PMID- 20581783 TI - Estrogen analogues: promising target for prevention and treatment of esophageal squamous cell carcinoma in high risk areas. AB - Esophageal cancer (EC) is one of the six most common cancers across the world. The striking 3-4: 1male predominance of esophageal squamous cell carcinoma (ESCC) has not yet been well explained. Our hypothesis is that the changes in level of estrogen and/or subtype of estrogen receptor (ER) may exert a protective factor in esophageal carcinogenesis and thus estrogen analogues may represent a promising target for prevention and treatment of ESCC. Several lines of evidence in a mouse ESCC model have suggested an inhibitory role of estrogen in ESCC growth and development. Consistent with this, our results showed that male and female counterparts from a high incidence area (HIA) for EC had significantly decreased serum estradiol compared to healthy controls from a low incidence area (LIA). Moreover, serum level of estradiol of ESCC patients from the HIA were significantly lower compared to healthy controls from both HIA and LIA. Numerous studies indicate that relatively low androgen level, high estrogen level (environmental and endogenous) and ratio alteration of sex hormones are important factors explaining decreased ESCC incidence. Both ERalpha and ERbeta are ligands to estradiol with different effects on transcription at activator protein-1 sites. Estrogen exerts a suppressive effect, mainly through ERalpha in ESCC, and an accelerative function, mainly through ERbeta. Our hypothesis suggests that administration of novel potent estrogen analogues might be an effective measure for prevention and treatment of ESCC in HIA. PMID- 20581784 TI - Stabilizing ryanodine receptor type 2: a novel strategy for the treatment of atrial fibrillation. AB - We propose that stabilizing ryanodine receptor type 2 (RyR2) may be a novel strategy for the treatment of atrial fibrillation (AF). Sarcoplasmic reticulum (SR) dysfunction caused by hyperphosphorylation of RyR2 and/or partial depletion of the stabilizing subunit calstabin2 has been indicated in AF. RyR2 stabilization may prevent SR dysfunction and thereby protect the heart from damage. Hypertrophy, hyperthyroidism and heart failure, three common pathological conditions associated with AF, result in increased SR Ca(2+) leak via RyR2. RyR2 stabilization may prevent SR Ca(2+) leak and thereby prevent AF. Triggered activity appears to underlie atrial ectopic foci, which cause AF. Diastolic Ca(2+) leak from SR via RyR2 may initiate triggered activity. Therefore, modulating RyR2 opening probability would be predicted to protect against triggered activity. Atrial oxidative stress plays a contributing role in the pathogenesis of AF. RyR2 is a target of reactive oxygen species, and chronic RyR2 oxidation increases RyR2 opening probability in a more sustained, less reversible manner. Strategies that attenuate oxidative stress and protect against AF may also contribute to RyR2 stabilization. Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. Thus, it is reasonable to speculate that experimental approaches designed to improve RyR2 stabilization will drive a novel conceptual revolution in AF drug development and lead to new clinical investigations. PMID- 20581785 TI - Assessment of coronary artery calcification using dual-source computed tomography in adult asymptomatic patients with type 1 diabetes mellitus. AB - BACKGROUND: Experience with dual-source computed tomography (DSCT) for detecting coronary artery calcification (CAC) in patients with type 1 diabetes is limited. MATERIAL/METHODS: A non-contrast DSCT scan was acquired in 46 type 1 diabetic patients. All scans were suitable for evaluating CAC expressed in Agatston-scores (effective radiation dose 0.66 [0.59-0.81] mSv; median [interquartile range]). RESULTS: In 21 patients Agatston scores were > or =1 (range 1-2353), while 25 patients had no detectable calcium deposits in the coronary arteries. Patients with vs. without CAC had higher age (52 [44-59] vs. 41 [38-48] yrs; p=0.0045), longer duration of diabetes (25.3 [23.4-36.3] vs. 23.3 [15.7-30.4] yrs; p=0.0238), greater waist circumference (88 [77-98] vs. 79 [75-87] cm; p=0.0147) and BMI (26.7 [24.5-28.4] vs. 22.6 [21.7-25.6] kg/m(2); p=0.0109). Moreover, patients with vs. without detectable CAC had higher serum LDL-cholesterol (3.35 [3.15-3.53] vs. 2.92 [2.62-3.33] mmol/l; p=0.0069) and serum uric acid values (236 [191-266] vs. 200 [170-219] micromol/l; p=0.0437). Hypertension was more frequent (p=0.0144) in patients with than without CAC. The 2 subgroups did not differ in long-term average HbA1c values (7.97 [7.30-8.56] vs. 8.06 [7.24-9.05]%; p=0.7491); however, estimated insulin sensitivity (estimated glucose disposal rate) was lower in patients with vs. without detectable CAC (7.43 [5.73-8.58] vs. 9.24 [8.22-10.72] mg/kg/min; p=0.0017). CONCLUSIONS: Non-invasive detection of CAC is feasible with a low dose DSCT scan. CAC in type 1 diabetic patients is associated with cardiovascular risk factors rather than with long-term glycemic control. PMID- 20581786 TI - Diabetes reduces auditory sensitivity in middle-aged listeners more than in elderly listeners: a population- based study of age-related hearing loss. AB - BACKGROUND: Diabetes mellitus (DM) and hearing impairment are both highly prevalent in older adult populations, but how the impact of diabetes on hearing varies by age is not well-studied. MATERIAL/METHODS: The subjects were 2306 adults aged 40 to 86 years who participated in a population-based study of aging, and were divided into 2 age groups, 40-64 years and 65-86 years, for cross sectional analysis. Air-conduction pure-tone thresholds at octave intervals from 125 to 8000 Hz were obtained. Outcomes were categorized in relation to presence or absence of DM. Hearing levels at 7 frequencies were set in the general linear model as objective variables with adjustment for confounders. Explanatory variables were age (<65 years vs. > or =65 years), DM (absence vs. presence), and interaction between age and DM. RESULTS: A statistically-significant adverse effect of DM on hearing was observed. This effect varied by age at the higher frequencies. The DM-age interaction was not synergistic at any test frequencies. No significant effects of the DM-age interaction were observed below 4000 Hz. In contrast, significant reciprocal effects of the DM-by-age interaction were found at 4000 Hz and 8000 Hz. Diabetes may accordingly affect higher-frequency hearing more strongly in the younger age-bracket. CONCLUSIONS: This study demonstrated that diabetes detrimentally affected hearing in community-dwelling middle-aged and elderly people, and that the effect of diabetes on higher-frequency hearing might be stronger in middle age. Screening for hearing impairment in diabetic patients may provide benefits for intervention or prevention of early presbycusis, particularly in this age group. PMID- 20581787 TI - The effect of N-acetylcysteine on blood pressure and markers of cardiovascular risk in non-diabetic patients with chronic kidney disease: a placebo-controlled, randomized, cross-over study. AB - BACKGROUND: Cardiovascular complications in patients with chronic kidney disease (CKD) are frequent. They show increased cardiovascular mortality and morbidity attributable to accumulation of several risk factors; e.g., hypertension, oxidative stress and elevated plasma homocysteine concentration. Despite recent progress in their management, there is still no optimal therapy that can stop progression of CKD and decrease cardiovascular outcome in these patients. Antioxidants, e.g., N-acetylcysteine (NAC), have been suggested as a promising medicament in this field. MATERIAL/METHODS: In a placebo-controlled, randomized, two-period cross-over study we evaluated the influence of eight weeks of NAC therapy (1200 mg/day) added to pharmacological renin-angiotensin system blockade on ambulatory blood pressure and surrogate markers of cardiovascular risk and injury in 20 non-diabetic patients with albuminuria [30-915 mg per creatinine mg] and normal or slightly decreased kidney function [eGFR 61-163 ml/min]. After eight weeks run-in period during which the therapy using angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers was settled, patients were randomly assigned to one of two treatment sequences: NAC/washout/placebo or placebo/washout/NAC. RESULTS: No significant changes in blood pressure, albuminuria and homocysteine plasma level were observed. CONCLUSIONS: NAC had no effect on blood pressure and surrogate markers of cardiovascular injury in non diabetic patients with CKD. PMID- 20581788 TI - Acute aortic dissection: microenvironmental regulation. AB - With the exception of certain genetic connective tissue disorders, acute aortic dissections are still often thought to occur randomly. Very few of these events fall under the genetic category such as Marfan's disease, Ehlers Danlos type IV or Loeys Dietz syndrome and the vast majority follows the rules of other catastrophic vascular events. The evidence is mounting that these catastrophes do not happen at random. This brief review looks at the evidence regarding a circadian, seasonal and weekly rhythm particularly of acute aortic dissections but also other vascular events including their association with emotional stress. The recent surge of interest in aortic diseases and particularly the establishment of the IRAD registry have lead to new insights and clarification of these events. While hormonal associations with vascular events have been known for more than thirty years, modern molecular examinations about regulatory pathways are mostly still lacking. The steering of circadian variation is accepted but poorly understood. On the basis of vascular neuroimmunological observations, speculations regarding micro environmental regulatory pathways are offered. PMID- 20581789 TI - Ghrelin, another factor affecting bone metabolism. AB - Ghrelin is a 28 amino acid peptide, identified in the stomach of rats and humans, in 1999. It is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) that strongly stimulates release of growth hormone at the hypothalamus pituitary axis. In humans, ghrelin exerts a variety of different endocrine and paracrine actions; from increasing food intake (orexigenic effect) to modulating energy homeostasis. It has been proved that ghrelin affects bone metabolism acting by an autocrine/paracrine mode, independent of GH/IGF-1 axis. Recently, ghrelin was identified in osteoblasts, stimulating proliferation and inhibiting apoptosis. Its expression also was confirmed in rat and human cartilage, being prevalently localized in the proliferative and maturative zone of the epiphyseal growth plate (which further supports the hypothesis of ghrelin's action as a growth factor for chondrocytes). Ghrelin also inhibits prostaglandin and/or leukotriene synthesis. Lately, ghrelin promotes osteogenesis of intramembranous bone and improves the repair of calvarial bone defect in rats in vivo. This review summarizes the effects of ghrelin on bone and cartilage metabolism, analyzes its direct and indirect actions on bone cells, and presents the clinical implication for its use. PMID- 20581790 TI - The efficacy and tolerability of once-daily controlled-release trazodone for depressed mood, anxiety, insomnia, and suicidality in major depressive disorder. AB - Trazodone Contramid(R) once-a-day (TzCOAD) is a reformulation of trazodone hydrochloride that controls the release of trazodone over 24 hours. A standard effect size analysis (Cohen's d) determined which items of the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) showed the greatest improvement in patients with major depressive disorder (MDD), following up to 8 weeks of therapy with TzCOAD. An additional insomnia analysis assessed whether the efficacy of TzCOAD is influenced by improvements in insomnia or baseline severity of insomnia. The analyses used data from a randomized study of 412 patients receiving 150-375 mg TzCOAD (N = 206) or placebo (N = 206). The results of the Cohen's d analysis on the modified intent to-treat population (LOCF) showed HAMD items with the greatest improvement were insomnia items (middle (-0.35), late (-0.24)), feelings of guilt (-0.24), and depressed mood (-0.23); for MADRS items they were reduced sleep (-0.31), inner tension (-0.22), reported sadness (-0.21), and suicidal thoughts (-0.21). An analysis of covariance showed no significant interaction between improvements in the HAMD Bech-6 core symptoms of depression and the baseline MADRS reduced sleep item or early changes in the HAMD-17 sleep disturbance factor. These results suggest that the antidepressant efficacy was independent of the baseline severity of insomnia and of the improvement in insomnia. Overall, the results elucidate the efficacy components and tolerability characteristics previously demonstrated for TzCOAD monotherapy for patients with MDD at the recommended daily dose of 300 mg. PMID- 20581791 TI - Early predictors of weight gain risk during treatment with olanzapine: analysis of pooled data from 58 clinical trials. AB - This analysis evaluated the usefulness of different predictors in identifying patient risk of substantial weight gain (SWG) during olanzapine treatment. Data were from 58 studies with 3826 patients diagnosed with schizophrenia, schizophrenia spectrum disorders, bipolar mania, bipolar depression, or borderline personality disorder. The primary definition for SWG was gaining >/=12% of baseline weight by endpoint (30 weeks +/-5 weeks); other definitions of SWG were also examined. Potential predictors of SWG included baseline patient characteristics, weight change, and percent weight change at Weeks 1, 2, 3, and 4 after olanzapine initiation. To facilitate model building and validation, the data set was randomly partitioned into training (N = 1912), validation (N = 1149), and test (N = 765) sets and 2 complementary analytic techniques were used: logistic regression with stepwise variable selection followed by receiver operating characteristic analysis for evaluation of resulting candidate models and decision trees. Approximately 24% of patients gained >/=12% of their initial weight, about 30% gained >/=10%, and 45% gained >/=7% or >/=5 kg by the 30-week endpoint. Baseline covariates significantly and positively associated with probability of SWG were lower baseline body mass index, younger age, female sex, United States residency, and African ethnicity. Early weight changes substantially improved the prediction of the risk for longer-term SWG. These results confirm that cut-offs for weight gain during the first 4 weeks of treatment may be useful in evaluating SWG risk for an individual patient. PMID- 20581792 TI - Differences in efficacy on substance abuse between risperidone and clozapine supports the importance of differential modulation of dopaminergic neurotransmission. AB - In patients with a psychotic disorder, substance abuse is a major problem. Substance abuse is associated with changes in dopaminergic neurotransmission of dopamine D1 and D2 receptors. Differences in efficacy between antipsychotics on substance abuse could be explained by differences in D2 receptor occupancy rate, differences in dissociation rate of the dopamine D2 receptor and differences in D1/D2 receptor occupancy ratio. Since clozapine and risperidone show a maximal difference in these properties, we review the effect of these antipsychotics on substance abuse. The results suggest a superior effect of clozapine for the long term treatment of substance abuse. This could support the hypothesis that low occupancy of the dopamine D2 receptor, a high dissociation rate and a high D1/D2 receptor ratio is related to efficacy on substance abuse. The results of this review suggest that clozapine could be considered as the medication of first choice in treating patients with substance use disorder. PMID- 20581793 TI - Catatonia and CPK elevation in neurosyphilis: role of plural pharmacodynamic mechanisms. AB - OBJECTIVES: To report catatonia in neurosyphilis with elevated creatine phosphokinase (CPK) and to understand the pharmacodynamics of catatonia. EXPERIMENTAL DESIGN: Case Report. PRINCIPAL OBSERVATIONS: We encountered catatonia in a man with neurosyphilis after increasing aripiprazole and valproate (drugs reported to improve catatonia) and reducing doxycycline and temazepam dosages, consistent with identified dopamine D2, serotonin 5HT2, and 5HT1a (aripiprazole), GABA-B (valproate), glutamatergic NMDA (aripiprazole, valproate, doxycycline), and GABA-A (aripiprazole, temazepam) mechanisms of catatonia. CPK was markedly elevated despite the absence of neuroleptic malignant syndrome (NMS) and responded to lorazepam, as did the catatonia. CONCLUSIONS: This appears to be the first case report of catatonia without NMS associated with each of the following: neurosyphilis, aripiprazole, and temazepam withdrawal. This case further adds to the emerging literature of catatonia arising with valproate and atypical antipsychotic co-administration, and of non-NMS catatonia associated with CPK elevations. Plural simultaneously - operant pharmacodynamic mechanisms may explain catatonia of unclear etiology and reconcile a seemingly contradictory literature (e.g., the capacity of certain drugs (e.g., aripiprazole, valproate) to either relieve or precipitate catatonia depending on their pharmacological contexts). Besides reduced D2, 5HT2, and GABA-A and increased 5HT1a, GABA-B, and NMDA receptor stimulation appreciated in the clinical literature, stimulation of adenosine, muscarinic, and H1 histamine receptors may also have promoted catatonia in this case and others, whereas the alpha-2 agonist clonidine has alleviated it. Multiple drugs in this regimen and our current reliance on mechanisms determined primarily in preclinical studies now indicate the need for clinical studies to determine the relative importance of each mechanism in human patients. PMID- 20581794 TI - Ziprasidone induced tardive cervical dystonia. AB - Fifty years old female patient used 80 mg/day ziprasidone for 4 months after diagnosed as atypical depression. After 4 months of ziprasidone treatment, involuntary movements appeared in her neck region. Ziprasidone was stopped in by tapering 20 mg/day, but the involuntary movements continued and even exacerbated. Then, oral clonazepam treatment was started but no improvement was observed. Finally, she was administered Botulinum Toxin A (BTX-A) treatment. After the fourth BTX-A injection therapy, significant reduction in neck pain and improvement of head deviation was observed. PMID- 20581795 TI - Amisulpride for clozapine induced sialorrhea. AB - Clozapine is an atypical and novel antipsychotic medication useful for patients with schizophrenia who are refractory to treatment. Its use is often associated with troublesome side effects like sialorrhea, sedation, weight gain, enuresis, dizziness, besides life threatening side effects like agranulocytosis. Drug treatments used for Clozapine induced sialorrhea (CIS) like anticholinergic drugs and alpha 2 receptor antagonists have their own added side effects. A case of CIS responding to low dose of Amisulpride is reported. PMID- 20581796 TI - Financial incentives to improve adherence to medication in five patients with schizophrenia in the Netherlands. AB - OBJECTIVE: Non-adherence to antipsychotic medication is common and increases the risk of psychotic relapse. A promising intervention may be a strategy wherein financial incentives are offered. METHODS: In a pilot study in The Netherlands, five patients with schizophrenia were offered financial incentives for a duration of one year to improve adherence to medication. Adherence and hospital days were measured. RESULTS: The percentage of accepted depot injections increased from an average of 44% in the previous year to 100% in the year when financial incentives were offered. While patients had been hospitalised for an average of 100.2 days in the previous year, only one was re-admitted for 17 days during the year of the intervention. CONCLUSIONS: The differences in adherence before and after the intervention were large and of clinical significance. However, randomised controlled trials are required to provide conclusive evidence on the effectiveness of offering financial incentives and potential consequences. PMID- 20581797 TI - A pilot study of the pharmacodynamic impact of SSRI drug selection and beta-1 receptor genotype (ADRB1) on cardiac vital signs in depressed patients: a novel pharmacogenetic approach. AB - OBJECTIVE: The adrenergic beta-1 receptor gene (ADRB1) Ser49Gly and Arg389Gly variants differentially affect blood pressure response to beta-blocker therapy. Binding site prediction results for fluoxetine and paroxetine in a bioinformatics model estimated that each of these particular selective serotonin reuptake inhibitors (SSRIs) have high receptor affinity as an "Adrenergic (beta) Blocker," which was confirmed in vitro. This pilot study was conducted to understand the relationship between these "beta-blocking" SSRIs (fluoxetine and paroxetine) and cardiac vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR)), when subjects are stratified by ADRB1 genotype. Previously ascertained DNA and clinical data was examined from 122 subjects recruited for a cross-sectional study of health and well being during SSRI pharmacotherapy. A multivariate linear regression analysis was used to determine which variables affected cardiac vital signs. There was a significant interaction between Arg389Gly variant status and "beta-blocking" SSRIs [p = 0.0353] in relation to SBP. Specifically in homozygous Arg389 subjects, those receiving "beta-blocking" SSRIs had significantly lower SBP (mean 104 mmHg) compared to the group taking other SSRIs (mean 122 mmHg) [p = 0.0437]. In these same homozygous Arg389 subjects, those receiving "beta-blocking" SSRIs also had lower HR (mean 60 bpm) compared to the other SSRIs (mean 79 bpm) [p = 0.00877]. Future prospective studies of this phenomenon are necessary to identify all genetic markers that can predict SSRI-associated cardiovascular effects that may be related to the SSRI discontinuation syndrome and potentially influence pharmacotherapy decisions. PMID- 20581799 TI - The effectiveness of long-acting injectable risperidone in a population of psychiatric out-patients: 1-year naturalistic study. AB - OBJECTIVE: A naturalistic, prospective study analyzed the effectiveness of long acting injectable risperidone (LAIR) in psychotic outpatients. METHODS: All outpatients (n = 53), affected by Schizophrenia and other Psychotic Disorders, who have begun LAIR at the Mental Health Service of Modena from December 1, 2005 to December 1, 2006, were collected. EXCLUSION CRITERIA: concomitant oral antipsychotic therapy at the 12th weeks (n = 16 patients) and treatment discontinuation (n = 12). The reasons of drop-out were analyzed. Clinical and demographic characteristics of outpatients (n = 25), motivations, implementation and adverse effects of LAIR treatment were evaluated. MAIN OUTCOME: the improvement of symptoms (25% reduction of BPRS and CGI-S scale score from baseline) and functioning level (50% increase of GAF scale score from baseline) at 6th (T6) and 12th (T12) month of LAIR therapy. Secondary outcome: reduction of the hospitalization days during the 1-year LAIR treatment in comparison to the previous year ones of the same patients. RESULTS: The final BPRS, CGI-S and GAF scores both at T6 and T12 showed a statistically significant difference from baseline (p < 0.0001, t-test). The frequency of improved patients in BPRS, CGI-S and GAF scales were 60%, 68%, 52% at T6, and 72%, 54%, 56% at T12, respectively. Side effects were represented by weight increase (4%), orthostatic hypotension (8%) and EPS (4%). The hospitalization days were statistically significant reduced during the 1-year LAIR treatment in comparison to the previous year ones (p < 0.05, t-test). CONCLUSION: Our data, limited by the small sample and the naturalistic methodology, suggest that 1-year LAIR treatment may be effective and safe. PMID- 20581798 TI - Predictors of non-stabilization during the combination therapy of lithium and divalproex in rapid cycling bipolar disorder: a post-hoc analysis of two studies. AB - OBJECTIVE: To study predictors of non-stabilization (i.e., not bimodally stabilized for randomization or not randomized due to premature discontinuation) during open-label treatment with lithium and divalproex in patients with rapid cycling bipolar disorder (RCBD) with or without comorbid recent substance use disorders (SUDs). METHOD: Data from the open-label phase of two maintenance studies were used. The reasons for non-stabilization were compared between patients with a recent SUD and those without. Predictors for non-stabilization were explored with logistic regression analyses. RESULTS: Of 149 patients with recent SUD and 254 without recent SUD enrolled into the open-label acute stabilization phase, 21% and 24% were stabilized and randomized, respectively. Compared to those without recent SUD, patients with recent SUD were more likely to discontinue the study due to non-adherence to the protocol, 53% versus 37% (OR = 1.92) or refractory mania/hypomania, 15% versus 9% (OR = 1.87), but less likely due to refractory depression 16% versus 25% (OR = 0.58) or adverse events, 10% versus19% (OR = 0.44). A history of recent SUDs, early life verbal abuse, female gender, and late onset of first depressive episode were associated with increased risk for non-stabilization with ORs of 1.85, 1.74, 1.10, and 1.04, respectively. CONCLUSIONS: During open treatment with lithium and divalproex in patients with RCBD, a recent SUD, a lifetime history of verbal abuse, female gender, and late onset of first depression independently predicted nonstabilization. The non stabilization for patients with SUD was related to non-adherence and refractory mania/hypomania. PMID- 20581800 TI - Signal detection and placebo response in schizophrenia: parallels with depression. AB - OBJECTIVE: Placebo response and the rate of failed clinical trials are increasing in schizophrenia, resembling previous experience with antidepressant clinical trials. In depression, the percent of patients randomized to placebo was shown to be strongly associated with drug-placebo differences (signal detection).We hypothesized that this factor would also be important in recent schizophrenia clinical trials. To test this hypothesis a database of acute schizophrenia placebo-controlled studies conducted between 1997 and 2008 was constructed. The database contained 27 studies, with 79 active treatment arms. As percentage of patients randomized to placebo increased, mean placebo improvement decreased (p = 0.047) and mean drug-placebo differences tended to increase (p = 0.166). The frequency of significant contrasts from studies with >= 25% randomized to placebo was 83.3%, compared with 58.3% in studies with <25% randomized to placebo. Caveats to these findings include limited data and confounding of potentially influential factors. These limitations prevent definitive conclusions. However, results are consistent with previous findings in depression where having a higher percent of patients randomized to placebo increased drug-placebo differences. PMID- 20581801 TI - Effectiveness of a brain-computer interface based programme for the treatment of ADHD: a pilot study. AB - Majority of children with attention deficit hyperactivity disorder (ADHD) have significant inattentive symptoms. We developed a progressive series of activities involving brain-computer interface-based games which could train users to improve their concentration. This pilot study investigated if the intervention could be utilized in children and if it could improve inattentive symptoms of ADHD. Ten medication-naive children aged 7 to 12 diagnosed with ADHD (combined or inattentive subtypes) received 20 sessions of therapy over a 10-week period. They were compared with age- and gendermatched controls. Both parent and teacher-rated inattentive score on the ADHD Rating Scale-IV improved more in the intervention group. A larger scale trial is warranted to further investigate the efficacy of our treatment programme in treating ADHD. PMID- 20581802 TI - NANOG regulates glioma stem cells and is essential in vivo acting in a cross functional network with GLI1 and p53. AB - A cohort of genes associated with embryonic stem (ES) cell behaviour, including NANOG, are expressed in a number of human cancers. They form an ES-like signature we first described in glioblastoma multiforme (GBM), a highly invasive and incurable brain tumour. We have also shown that HEDGEHOG-GLI (HH-GLI) signalling is required for GBM growth, stem cell expansion and the expression of this (ES) like stemness signature. Here, we address the function of NANOG in human GBMs and its relationship with HH-GLI activity. We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation, and is regulated by HH-GLI signalling. However, GLI1 also requires NANOG activity forming a positive loop, which is negatively controlled by p53 and vice versa. NANOG is essential for GBM tumourigenicity in orthotopic xenografts and it is epistatic to HH-GLI activity. Our data establish NANOG as a novel HH-GLI mediator essential for GBMs. We propose that this function is conserved and that tumour growth and stem cell behaviour rely on the status of a functional GLI1-NANOG-p53 network. PMID- 20581803 TI - Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase. AB - Glucose is the preferred carbon source for most cell types and a major determinant of cell growth. In yeast and certain mammalian cells, glucose activates the cAMP-dependent protein kinase A (PKA), but the mechanisms of PKA activation remain unknown. Here, we identify cytosolic pH as a second messenger for glucose that mediates activation of the PKA pathway in yeast. We find that cytosolic pH is rapidly and reversibly regulated by glucose metabolism and identify the vacuolar ATPase (V-ATPase), a proton pump required for the acidification of vacuoles, as a sensor of cytosolic pH. V-ATPase assembly is regulated by cytosolic pH and is required for full activation of the PKA pathway in response to glucose, suggesting that it mediates, at least in part, the pH signal to PKA. Finally, V-ATPase is also regulated by glucose in the Min6 beta cell line and contributes to PKA activation and insulin secretion. Thus, these data suggest a novel and potentially conserved glucose-sensing pathway and identify a mechanism how cytosolic pH can act as a signal to promote cell growth. PMID- 20581804 TI - Hedgehog controls neural stem cells through p53-independent regulation of Nanog. AB - Hedgehog (Hh) pathway has a pivotal function in development and tumorigenesis, processes sustained by stem cells (SCs). The transcription factor Nanog controls stemness acting as a key determinant of both embryonic SC self-renewal and differentiated somatic cells reprogramming to pluripotency, in concert with the loss of the oncosuppressor p53. How Nanog is regulated by microenvironmental signals in postnatal SC niches has been poorly investigated. Here, we show that Nanog is highly expressed in SCs from postnatal cerebellum and medulloblastoma, and acts as a critical mediator of Hh-driven self-renewal. Indeed, the downstream effectors of Hh activity, Gli1 and Gli2, bind to Nanog-specific cis-regulatory sequences both in mouse and human SCs. Loss of p53, a key event promoting cell stemness, activates Hh signalling, thereby contributing to Nanog upregulation. Conversely, Hh downregulates p53 but does not require p53 to control Nanog. Our data reveal a mechanism for the function of Hh in the control of stemness that represents a crucial component of an integrated circuitry determining cell fate decision and involved in the maintenance of cancer SCs. PMID- 20581805 TI - Prognostic significance of HER2 expression in neuroblastic tumors. AB - HER2 is essential for normal embryonic development and has a critical function in oncogenesis and progression of some types of cancer. Neuroblastic tumors create a heterogenous group of pediatric embryonal tumors of sympathoadrenal lineage. The biological and prognostic function of HER2 in these tumors is not well established. In this study, we evaluated the status of HER2, its prognostic significance, and clinicopathological correlations in series of 79 untreated neuroblastoma. The immunohistochemical assessment of HER2 and Ki-67 (proliferation index) as well as HER2 copy number status were performed on tissue microarrays. HER2 expression characterized 63 tumors, including 34 with low and 29 with high level, showing either membranous or mixed membranous-cytoplasmic pattern. Sixteen cases were HER2 immunonegative. The pattern of immunolabeling depended on the maturity of neuroblastic cells, being the most intense in differentiating neuroblasts. None of the tumors revealed HER2 amplification. In the examined group, 20% of patients died of disease from 4 to 107 months (median 18) from the diagnosis, and the survivors were followed up for 14-149 months (median 59). Patients' age, stage of disease, tumor location, mitosis/karyorrhexis index (MKI), and presence of HER2 expression were statistically significantly related to survival probability as detected by the Cox proportional hazard model. In the univariate analysis, Kaplan-Meier curves revealed significantly poorer outcome of HER2 negative than HER2-positive tumors (either low or high expression). The immunonegativity was associated with adverse clinicopathological parameters, including poor survival, metastatic stage of disease, un- or poorly differentiated histology, high MKI, and higher proliferation index. In conclusion, HER2 expression, not accompanied by gene amplification, is common in neuroblastic tumors. HER2 positivity seems to have a positive prognostic significance. HER2 expression with a variable pattern is a marker of the stage of neuroblastic cells differentiation. PMID- 20581806 TI - Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay. AB - Myxoid/round cell liposarcoma is characterized by the recurrent translocations t(12;16)(q13;p11) and, less commonly, t(12;22)(q13;q12), which fuse FUS or EWSR1, respectively, to DDIT3 on chromosome 12. Although a number of different variant breakpoints have been described, greater than 90% of all cases have one of the three different FUS-DDIT3 fusions, which may have clinical significance. To identify the individual breakpoints, a sequence-specific assay such as reverse transcription-PCR (RT-PCR) is needed. In this study, we optimized primer design to develop an RT-PCR assay for the detection of the most common translocations in formalin-fixed paraffin-embedded tissue specimens. We compared our assay with primers previously published for testing formalin-fixed paraffin-embedded specimens and achieved the most consistent results with our primers. We obtained RNA from 32 MLS cases, of which 27 carried one of the three common FUS-DDIT3 chimeric transcript types. Four of the negative cases were from very small biopsies with very low RNA concentration. One case was consistently negative by RT-PCR, but showed a FUS rearrangement by fluorescent in situ hybridization, suggesting that it may harbor one of the rarer FUS-DDIT3 chimeric types. In addition to the common fusions, our assay also identified a novel FUS-DDIT3 fusion between exon 9 of FUS and exon 3 of DDIT3 in one of the cases. PMID- 20581807 TI - Histological features of medullary carcinoma and prognosis in triple-negative basal-like carcinomas of the breast. AB - Medullary carcinomas have a better prognosis than other grade 3 mammary carcinomas, but they typically show basal-like biological features, which are associated with a poor prognosis. In this study we examined the associations and prognostic relevance of medullary histological features in a series of 165 invasive carcinomas with a basal-like phenotype: triple-negative (oestrogen receptor, progesterone receptor, HER2) and expressing at least one basal marker (CK5/6, CK14, CK17 or EGFR). The following histological features were associated with each other: prominent inflammation, anastomosing sheets, absence of fibrosis, absence of infiltrative margin and absence of gland formation. Prominent inflammation and anastomosing sheets in at least 30% of the tumour were associated with a better prognosis on univariate analysis. The combination of these two features (a simplified definition of medullary-like type) was present in 17% of tumours and was an independent prognostic factor on multivariate analysis. This simplified definition had good inter-observer reproducibility (kappa=0.61) and is worthy of more detailed assessment in an unselected group of mammary carcinomas. A fibrotic focus was present in 36% of carcinomas. Only 3% of tumours with a fibrotic focus had features of medullary-like carcinomas. Fibrotic focus of greater than 30% of the tumour was associated with a poor prognosis. This study emphasizes the heterogeneity of morphology and behaviour of triple negative basal-like carcinomas. PMID- 20581808 TI - Culture clash on consent. AB - All research on human subjects requires their informed consent. Obtaining valid consent from isolated minorities can be particularly challenging, but scientists need to avoid the temptingly easy way out, so as to prevent further exclusion of these vulnerable populations from biomedical research. PMID- 20581809 TI - Central melanocortin signaling regulates cholesterol. PMID- 20581810 TI - Neuronal protein economics: keeping tabs on synthesis. PMID- 20581811 TI - Needling adenosine receptors for pain relief. PMID- 20581812 TI - The Na+ channel conundrum: axon structure versus function. PMID- 20581813 TI - Focus on neurodegeneration. PMID- 20581814 TI - Genome-wide association studies: the key to unlocking neurodegeneration? AB - The successful discovery of genes that cause rare monogenic disorders has dominated our understanding of the genetic basis of neurodegenerative disease. The emergence of robust genome-wide association methodologies promises to explain the genetic etiology of the common sporadic forms of complex diseases. In addition to revealing the genetic susceptibility of neurodegenerative disease, genome-wide association studies (GWASs) should also be an unbiased generator of molecules that are relevant in disease pathogenesis. Despite this exciting potential, GWAS results have varied in their consistency and their ability to deliver these aims. The largest challenge that faces neuroscientists is the interpretation of the results of GWASs and the translation of the genetic findings into functional mechanisms that are biologically important in disease pathogenesis and, ultimately, treatment design. We examine recent results from GWASs of Alzheimer's disease and Parkinson's disease and explore their use and limitations. We further reflect on how these results may expedite progress in understanding and influencing the molecular pathogenesis of neurodegeneration. PMID- 20581815 TI - Therapy development in spinal muscular atrophy. AB - Proximal spinal muscular atrophy (SMA) is the predominant form of motor neuron disease in children and young adults. In contrast to other neurodegenerative disorders, SMA is a genetically homozygous autosomal recessive disease that is caused by deficiency of the survival motor neuron (SMN) protein. This homogeneity should in principle facilitate therapy development. Previous therapy approaches have focused on upregulation of SMN expression from a second SMN (SMN2) gene that gives rise to low amounts of functional SMN protein. Drug development to target disease-specific mechanisms at cellular and physiological levels is in its early stages, as the pathophysiological processes that underlie the main disease symptoms are still not fully understood. Mouse models have helped to make conceptual progress in the disease mechanism, but their suitability in the search for therapeutic agents remains to be validated--an issue that is ubiquitous to the translational therapeutic research of other neurodegenerative diseases. Human induced pluripotent stem cell technology for generation of large numbers of human motor neurons could help to fill this gap and advance the power of drug screening. In parallel, advances in oligonucleotide technologies for engineering SMN2 pre-mRNA splicing are approaching their first clinical trials, whose success depends on improved technologies for drug delivery to motor neurons. If this obstacle can be overcome, this could boost therapy development, not only for SMA but also for other neurodegenerative disorders. PMID- 20581816 TI - What can pluripotent stem cells teach us about neurodegenerative diseases? AB - Neurodegenerative diseases represent a growing public health challenge. Current medications treat symptoms, but none halt or retard neurodegeneration. The recent advent of pluripotent cell biology has opened new avenues for neurodegenerative disease research. The greatest potential for induced pluripotent cells derived from affected individuals is likely to be their utility for modeling and understanding the mechanisms underlying neurodegenerative processes, and for searching for new treatments, including cell replacement therapies. However, much work remains to be done before pluripotent cells can be used for preclinical and clinical applications. Here we discuss the challenges of generating specific neural cell subtypes from pluripotent stem cells, the use of pluripotent stem cells to model both cell-autonomous and non-cell-autonomous mechanisms of neurodegeneration, whether adult-onset neurodegeneration can be emulated in short term cultures and the hurdles of cell replacement therapy. Progress in these four areas will substantially accelerate effective application of pluripotent stem cells. PMID- 20581817 TI - Autophagy gone awry in neurodegenerative diseases. AB - Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets. PMID- 20581818 TI - Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. AB - Alzheimer's disease is the most frequent neurodegenerative disorder and the most common cause of dementia in the elderly. Diverse lines of evidence suggest that amyloid-beta (Abeta) peptides have a causal role in its pathogenesis, but the underlying mechanisms remain uncertain. Here we discuss recent evidence that Abeta may be part of a mechanism controlling synaptic activity, acting as a positive regulator presynaptically and a negative regulator postsynaptically. The pathological accumulation of oligomeric Abeta assemblies depresses excitatory transmission at the synaptic level, but also triggers aberrant patterns of neuronal circuit activity and epileptiform discharges at the network level. Abeta induced dysfunction of inhibitory interneurons likely increases synchrony among excitatory principal cells and contributes to the destabilization of neuronal networks. Strategies that block these Abeta effects may prevent cognitive decline in Alzheimer's disease. Potential obstacles and next steps toward this goal are discussed. PMID- 20581819 TI - Negative plant-soil feedback predicts tree-species relative abundance in a tropical forest. AB - The accumulation of species-specific enemies around adults is hypothesized to maintain plant diversity by limiting the recruitment of conspecific seedlings relative to heterospecific seedlings. Although previous studies in forested ecosystems have documented patterns consistent with the process of negative feedback, these studies are unable to address which classes of enemies (for example, pathogens, invertebrates, mammals) exhibit species-specific effects strong enough to generate negative feedback, and whether negative feedback at the level of the individual tree is sufficient to influence community-wide forest composition. Here we use fully reciprocal shade-house and field experiments to test whether the performance of conspecific tree seedlings (relative to heterospecific seedlings) is reduced when grown in the presence of enemies associated with adult trees. Both experiments provide strong evidence for negative plant-soil feedback mediated by soil biota. In contrast, above-ground enemies (mammals, foliar herbivores and foliar pathogens) contributed little to negative feedback observed in the field. In both experiments, we found that tree species that showed stronger negative feedback were less common as adults in the forest community, indicating that susceptibility to soil biota may determine species relative abundance in these tropical forests. Finally, our simulation models confirm that the strength of local negative feedback that we measured is sufficient to produce the observed community-wide patterns in tree-species relative abundance. Our findings indicate that plant-soil feedback is an important mechanism that can maintain species diversity and explain patterns of tree-species relative abundance in tropical forests. PMID- 20581820 TI - Single-cell NF-kappaB dynamics reveal digital activation and analogue information processing. AB - Cells operate in dynamic environments using extraordinary communication capabilities that emerge from the interactions of genetic circuitry. The mammalian immune response is a striking example of the coordination of different cell types. Cell-to-cell communication is primarily mediated by signalling molecules that form spatiotemporal concentration gradients, requiring cells to respond to a wide range of signal intensities. Here we use high-throughput microfluidic cell culture and fluorescence microscopy, quantitative gene expression analysis and mathematical modelling to investigate how single mammalian cells respond to different concentrations of the signalling molecule tumour-necrosis factor (TNF)-alpha, and relay information to the gene expression programs by means of the transcription factor nuclear factor (NF)-kappaB. We measured NF-kappaB activity in thousands of live cells under TNF-alpha doses covering four orders of magnitude. We find, in contrast to population-level studies with bulk assays, that the activation is heterogeneous and is a digital process at the single-cell level with fewer cells responding at lower doses. Cells also encode a subtle set of analogue parameters to modulate the outcome; these parameters include NF-kappaB peak intensity, response time and number of oscillations. We developed a stochastic mathematical model that reproduces both the digital and analogue dynamics as well as most gene expression profiles at all measured conditions, constituting a broadly applicable model for TNF-alpha induced NF-kappaB signalling in various types of cells. These results highlight the value of high-throughput quantitative measurements with single-cell resolution in understanding how biological systems operate. PMID- 20581821 TI - Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. AB - The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal (also known as neutrophil gelatinase associated lipocalin, siderocalin, lipocalin 2) sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions. Using chemical screens, crystallography and fluorescence methods, we report that Scn-Ngal binds iron together with a small metabolic product called catechol. The formation of the complex blocked the reactivity of iron and permitted its transport once introduced into circulation in vivo. Scn-Ngal then recycled its iron in endosomes by a pH-sensitive mechanism. As catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal catechol-Fe(III) complex represents an unforeseen microbial-host interaction, which mimics Scn-Ngal-siderophore interactions but instead traffics iron in aseptic tissues. These results identify an endogenous siderophore, which may link the disparate roles of Scn-Ngal in different diseases. PMID- 20581822 TI - Transcriptional regulation by small RNAs at sequences downstream from 3' gene termini. AB - Transcriptome studies reveal many noncoding transcripts overlapping 3' gene termini. The function of these transcripts is unknown. Here we have characterized transcription at the progesterone receptor (PR) locus and identified noncoding transcripts that overlap the 3' end of the gene. Small RNAs complementary to sequences beyond the 3' terminus of PR mRNA modulated expression of PR, recruited argonaute 2 to a 3' noncoding transcript, altered occupancy of RNA polymerase II, induced chromatin changes at the PR promoter and affected responses to physiological stimuli. We found that the promoter and 3' terminal regions of the PR locus are in close proximity, providing a potential mechanism for RNA-mediated control of transcription over long genomic distances. These results extend the potential for small RNAs to regulate transcription to target sequences beyond the 3' termini of mRNA. PMID- 20581823 TI - Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I. AB - RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24 mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response. PMID- 20581824 TI - Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction. AB - Repression of gene transcription by the nuclear receptor Rev-erbalpha plays an integral role in the core molecular circadian clock. We report the crystal structure of a nuclear receptor-co-repressor (N-CoR) interaction domain 1 (ID1) peptide bound to truncated human Rev-erbalpha ligand-binding domain (LBD). The ID1 peptide forms an unprecedented antiparallel beta-sheet with Rev-erbalpha, as well as an alpha-helix similar to that seen in nuclear receptor ID2 crystal structures but out of register by four residues. Comparison with the structure of Rev-erbbeta bound to heme indicates that ID1 peptide and heme induce substantially different conformational changes in the LBD. Although heme is involved in Rev-erb repression, the structure suggests that Rev-erbalpha could also mediate repression via ID1 binding in the absence of heme. The previously uncharacterized secondary structure induced by ID1 peptide binding advances our understanding of nuclear receptor-co-repressor interactions. PMID- 20581825 TI - HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues. AB - HtrA proteases are tightly regulated proteolytic assemblies that are essential for maintaining protein homeostasis in extracytosolic compartments. Though HtrA proteases have been characterized in detail, their precise molecular mechanism for switching between different functional states is still unknown. To address this, we carried out biochemical and structural studies of DegP from Escherichia coli. We show that effector-peptide binding to the PDZ domain of DegP induces oligomer conversion from resting hexameric DegP6 into proteolytically active 12 mers and 24-mers (DegP12/24). Moreover, our data demonstrate that a specific protease loop (L3) functions as a conserved molecular switch of HtrA proteases. L3 senses the activation signal-that is, the repositioned PDZ domain of substrate engaged DegP12/24 or the binding of allosteric effectors to regulatory HtrA proteases such as DegS-and transmits this information to the active site. Implications for protein quality control and regulation of oligomeric enzymes are discussed. PMID- 20581826 TI - Determinants of structural and functional plasticity of a widely conserved protease chaperone complex. AB - Channeling of misfolded proteins into repair, assembly or degradation pathways is often mediated by complex and multifunctional cellular factors. Despite detailed structural information, the underlying regulatory mechanisms governing these factors are not well understood. The extracytoplasmic heat-shock factor DegP (HtrA) is a well-suited model for addressing mechanistic issues, as it is regulated by the common mechanisms of allostery and activation by oligomerization. Site-directed mutagenesis combined with refolding and oligomerization studies of chemically denatured DegP revealed how substrates trigger the conversion of the resting conformation into the active conformation. Binding of specific peptides to PDZ domain-1 causes a local rearrangement that is allosterically transmitted to the substrate-binding pocket of the protease domain. This activated state readily assembles into larger oligomeric particles, thus stabilizing the catalytically active form and providing a degradation cavity for protein substrates. The implications of these data for the mechanism of protein quality control are discussed. PMID- 20581829 TI - Simultaneous intracellular chloride and pH measurements using a GFP-based sensor. AB - Chloride and protons perform important closely related roles in many cellular responses. Here we developed a ratiometric biosensor, ClopHensor, based on a highly chloride-sensitive Aequorea victoria GFP variant that is suited for the combined real-time optical detection of pH changes and chloride fluxes in live cells. We detected high chloride concentration in large dense-core exocytosis granules by targeting ClopHensor to these intracellular compartments. PMID- 20581828 TI - Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks. AB - Not all tumor vessels are equal. Tumor-associated vasculature includes immature vessels, regressing vessels, transport vessels undergoing arteriogenesis and peritumor vessels influenced by tumor growth factors. Current techniques for analyzing tumor blood flow do not discriminate between vessel subtypes and only measure average changes from a population of dissimilar vessels. We developed methodologies for simultaneously quantifying blood flow (velocity, flux, hematocrit and shear rate) in extended networks at single-capillary resolution in vivo. Our approach relies on deconvolution of signals produced by labeled red blood cells as they move relative to the scanning laser of a confocal or multiphoton microscope and provides fully resolved three-dimensional flow profiles within vessel networks. Using this methodology, we show that blood velocity profiles are asymmetric near intussusceptive tissue structures in tumors in mice. Furthermore, we show that subpopulations of vessels, classified by functional parameters, exist in and around a tumor and in normal brain tissue. PMID- 20581830 TI - The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3. AB - Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter through activity at transcription factor AP-1-like sites. Interferon elicitors recruited the transcription factor IRF3 to the promoter, whereupon MafB acted as a transcriptional antagonist, impairing the interaction of coactivators with IRF3. Mathematical modeling supported the view that prepositioning of MafB on the promoter allows the system to respond rapidly to fluctuations in IRF3 activity. Higher expression of MafB in human pancreatic islet beta cells might increase cellular vulnerability to viral infections associated with the etiology of type 1 diabetes. PMID- 20581827 TI - Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. AB - By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. PMID- 20581831 TI - Antimicrobial activity of mucosal-associated invariant T cells. AB - Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) alpha-chain and restriction by the major histocompatibility complex (MHC) related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. This activation required cognate interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, we observed considerably fewer MAIT cells in blood from patients with bacterial infections such as tuberculosis. In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection. PMID- 20581832 TI - Nanomaterials in preventive dentistry. AB - The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges in dentistry. In recent years, biomimetic approaches have been used to develop nanomaterials for inclusion in a variety of oral health-care products. Examples include liquids and pastes that contain nano-apatites for biofilm management at the tooth surface, and products that contain nanomaterials for the remineralization of early submicrometre-sized enamel lesions. However, the treatment of larger visible cavities with nanomaterials is still at the research stage. Here, we review progress in the development of nanomaterials for different applications in preventive dentistry and research, including clinical trials. PMID- 20581833 TI - Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. AB - Recently, optical stimulation has begun to unravel the neuronal processing that controls certain animal behaviours. However, optical approaches are limited by the inability of visible light to penetrate deep into tissues. Here, we show an approach based on radio-frequency magnetic-field heating of nanoparticles to remotely activate temperature-sensitive cation channels in cells. Superparamagnetic ferrite nanoparticles were targeted to specific proteins on the plasma membrane of cells expressing TRPV1, and heated by a radio-frequency magnetic field. Using fluorophores as molecular thermometers, we show that the induced temperature increase is highly localized. Thermal activation of the channels triggers action potentials in cultured neurons without observable toxic effects. This approach can be adapted to stimulate other cell types and, moreover, may be used to remotely manipulate other cellular machinery for novel therapeutics. PMID- 20581834 TI - 'Soft' Au, Pt and Cu contacts for molecular junctions through surface-diffusion mediated deposition. AB - Virtually all types of molecular electronic devices depend on electronically addressing a molecule or molecular layer through the formation of a metallic contact. The introduction of molecular devices into integrated circuits will probably depend on the formation of contacts using a vapour deposition technique, but this approach frequently results in the metal atoms penetrating or damaging the molecular layer. Here, we report a method of forming 'soft' metallic contacts on molecular layers through surface-diffusion-mediated deposition, in which the metal atoms are deposited remotely and then diffuse onto the molecular layer, thus eliminating the problems of penetration and damage. Molecular junctions fabricated by this method exhibit excellent yield (typically >90%) and reproducibility, and allow examination of the effects of molecular-layer structure, thickness and contact work function. PMID- 20581835 TI - A molecular-imprint nanosensor for ultrasensitive detection of proteins. AB - Molecular imprinting is a technique for preparing polymer scaffolds that function as synthetic receptors. Imprinted polymers that can selectively bind organic compounds have proven useful in sensor development. Although creating synthetic molecular-imprinting polymers that recognize proteins remains challenging, nanodevices and nanomaterials show promise in this area. Here, we show that arrays of carbon-nanotube tips with an imprinted non-conducting polymer coating can recognize proteins with subpicogram per litre sensitivity using electrochemical impedance spectroscopy. We have developed molecular-imprinting sensors specific for human ferritin and human papillomavirus derived E7 protein. The molecular-imprinting-based nanosensor can also discriminate between Ca(2+) induced conformational changes in calmodulin. This ultrasensitive, label-free electrochemical detection of proteins offers an alternative to biosensors based on biomolecule recognition. PMID- 20581836 TI - Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. AB - Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Federation Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals. PMID- 20581837 TI - Serotonin regulates pancreatic beta cell mass during pregnancy. AB - During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, whereas prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta cells. However, the exact mechanisms by which the lactogenic hormones drive beta cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to stimulate beta cell proliferation. Expression of serotonin synthetic enzyme tryptophan hydroxylase-1 (Tph1) and serotonin production rose sharply in beta cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the G alpha(q)-linked serotonin receptor 5-hydroxytryptamine receptor-2b (Htr2b) in maternal islets increased during pregnancy and normalized just before parturition, whereas expression of the G alpha(i)-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes. PMID- 20581838 TI - Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions. AB - Epidermal homeostasis depends on a balance between stem cell renewal and differentiation and is regulated by extrinsic signals from the extracellular matrix (ECM). A powerful approach to analysing the pathways involved is to engineer single-cell microenvironments in which individual variables are precisely and quantitatively controlled. Here, we employ micropatterned surfaces to identify the signalling pathways by which restricted ECM contact triggers human epidermal stem cells to initiate terminal differentiation. On small (20 microm diameter) circular islands, keratinocytes remained rounded, and differentiated at higher frequency than cells that could spread on large (50 microm diameter) islands. Differentiation did not depend on ECM composition or density. Rather, the actin cytoskeleton mediated shape-induced differentiation by regulating serum response factor (SRF) transcriptional activity. Knockdown of SRF or its co-factor MAL inhibited differentiation, whereas overexpression of MAL stimulated SRF activity and involucrin expression. SRF target genes FOS and JUNB were also required for differentiation: c-Fos mediated serum responsiveness, whereas JunB was regulated by actin and MAL. Our findings demonstrate how biophysical cues are transduced into transcriptional responses that determine epidermal cell fate. PMID- 20581839 TI - Interplay between Cdh1 and JNK activity during the cell cycle. AB - The ubiquitin ligase APC/C(Cdh1) coordinates degradation of key cell cycle regulators. We report here that a nuclear-localized portion of the stress activated kinase JNK is degraded by the APC/C(Cdh1) during exit from mitosis and the G1 phase of the cell cycle. Expression of a non-degradable JNK induces prometaphase-like arrest and aberrant mitotic spindle dynamics. Moreover, JNK phosphorylates Cdh1 directly, during G2 and early mitosis, changing its subcellular localization and attenuating its ability to activate the APC/C during G2/M. This regulatory mechanism between JNK and Cdh1 reveals an important function for JNK during the cell cycle. PMID- 20581840 TI - cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification. AB - Neuronal differentiation is accomplished through cascades of intrinsic genetic factors initiated in neuronal progenitors by external gradients of morphogens. Activity has been thought to be important only late in development, but recent evidence suggests that activity also regulates early neuronal differentiation. Activity in post-mitotic neurons before synapse formation can regulate phenotypic specification, including neurotransmitter choice, but the mechanisms are not clear. We identified a mechanism that links endogenous calcium spike activity with an intrinsic genetic pathway to specify neurotransmitter choice in neurons in the dorsal embryonic spinal cord of Xenopus tropicalis. Early activity modulated transcription of the GABAergic/glutamatergic selection gene tlx3 through a variant cAMP response element (CRE) in its promoter. The cJun transcription factor bound to this CRE site, modulated transcription and regulated neurotransmitter phenotype via its transactivation domain. Calcium signaled through cJun N-terminal phosphorylation, which integrated activity dependent and intrinsic neurotransmitter specification. This mechanism provides a basis for early activity to regulate genetic pathways at critical decision points, switching the phenotype of developing neurons. PMID- 20581841 TI - Mechanisms of pattern decorrelation by recurrent neuronal circuits. AB - Decorrelation is a fundamental computation that optimizes the format of neuronal activity patterns. Channel decorrelation by adaptive mechanisms results in efficient coding, whereas pattern decorrelation facilitates the readout and storage of information. Mechanisms achieving pattern decorrelation, however, remain unclear. We developed a theoretical framework that relates high dimensional pattern decorrelation to neuronal and circuit properties in a mathematically stringent fashion. For a generic class of random neuronal networks, we proved that pattern decorrelation emerges from neuronal nonlinearities and is amplified by recurrent connectivity. This mechanism does not require adaptation of the network, is enhanced by sparse connectivity, depends on the baseline membrane potential and is robust. Connectivity measurements and computational modeling suggest that this mechanism is involved in pattern decorrelation in the zebrafish olfactory bulb. These results reveal a generic relationship between the structure and function of neuronal circuits that is probably relevant for pattern processing in various brain areas. PMID- 20581842 TI - Temporal context calibrates interval timing. AB - We use our sense of time to identify temporal relationships between events and to anticipate actions. The degree to which we can exploit temporal contingencies depends on the variability of our measurements of time. We asked humans to reproduce time intervals drawn from different underlying distributions. As expected, production times were more variable for longer intervals. However, production times exhibited a systematic regression toward the mean. Consequently, estimates for a sample interval differed depending on the distribution from which it was drawn. A performance-optimizing Bayesian model that takes the underlying distribution of samples into account provided an accurate description of subjects' performance, variability and bias. This finding suggests that the CNS incorporates knowledge about temporal uncertainty to adapt internal timing mechanisms to the temporal statistics of the environment. PMID- 20581843 TI - A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing. AB - Genetically targeted light-activated ion channels and pumps make it possible to determine the role of specific neurons in neuronal circuits, information processing and behavior. We developed a K+-selective ionotropic glutamate receptor that reversibly inhibits neuronal activity in response to light in dissociated neurons and brain slice and also reversibly suppresses behavior in zebrafish. The receptor is a chimera of the pore region of a K+-selective bacterial glutamate receptor and the ligand-binding domain of a light-gated mammalian kainate receptor. This hyperpolarizing light-gated channel, HyLighter, is turned on by a brief light pulse at one wavelength and turned off by a pulse at a second wavelength. The control is obtained at moderate intensity. After optical activation, the photocurrent and optical silencing of activity persists in the dark for extended periods. The low light requirement and bi-stability of HyLighter represent advantages for the dissection of neural circuitry. PMID- 20581844 TI - An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase. AB - The specificity of SCF ubiquitin ligase-mediated protein degradation is determined by F-box proteins. We identified a biplanar dicarboxylic acid compound, called SCF-I2, as an inhibitor of substrate recognition by the yeast F box protein Cdc4 using a fluorescence polarization screen to monitor the displacement of a fluorescein-labeled phosphodegron peptide. SCF-I2 inhibits the binding and ubiquitination of full-length phosphorylated substrates by SCF(Cdc4). A co-crystal structure reveals that SCF-I2 inserts itself between the beta strands of blades 5 and 6 of the WD40 propeller domain of Cdc4 at a site that is 25 A away from the substrate binding site. Long-range transmission of SCF-I2 interactions distorts the substrate binding pocket and impedes recognition of key determinants in the Cdc4 phosphodegron. Mutation of the SCF-I2 binding site abrogates its inhibitory effect and explains specificity in the allosteric inhibition mechanism. Mammalian WD40 domain proteins may exhibit similar allosteric responsiveness and hence represent an extensive class of druggable target. PMID- 20581845 TI - Chemical genetics screen for enhancers of rapamycin identifies a specific inhibitor of an SCF family E3 ubiquitin ligase. AB - The target of rapamycin (TOR) plays a central role in eukaryotic cell growth control. With prevalent hyperactivation of the mammalian TOR (mTOR) pathway in human cancers, strategies to enhance TOR pathway inhibition are needed. We used a yeast-based screen to identify small-molecule enhancers of rapamycin (SMERs) and discovered an inhibitor (SMER3) of the Skp1-Cullin-F-box (SCF)(Met30) ubiquitin ligase, a member of the SCF E3-ligase family, which regulates diverse cellular processes including transcription, cell-cycle control and immune response. We show here that SMER3 inhibits SCF(Met30) in vivo and in vitro, but not the closely related SCF(Cdc4). Furthermore, we demonstrate that SMER3 diminishes binding of the F-box subunit Met30 to the SCF core complex in vivo and show evidence for SMER3 directly binding to Met30. Our results show that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes. PMID- 20581846 TI - Engineered allosteric activation of kinases in living cells. AB - Studies of cellular and tissue dynamics benefit greatly from tools that can control protein activity with specificity and precise timing in living systems. Here we describe an approach to confer allosteric regulation specifically on the catalytic activity of protein kinases. A highly conserved portion of the kinase catalytic domain is modified with a small protein insert that inactivates catalytic activity but does not affect other protein functions (Fig. 1a). Catalytic activity is restored by addition of rapamycin or non-immunosuppresive rapamycin analogs. Molecular modeling and mutagenesis indicate that the protein insert reduces activity by increasing the flexibility of the catalytic domain. Drug binding restores activity by increasing rigidity. We demonstrate the approach by specifically activating focal adhesion kinase (FAK) within minutes in living cells and show that FAK is involved in the regulation of membrane dynamics. Successful regulation of Src and p38 by insertion of the rapamycin responsive element at the same conserved site used in FAK suggests that our strategy will be applicable to other kinases. PMID- 20581849 TI - Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models. AB - AIM: To investigate the potential antidepressant and anxiolytic effects of Neu P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. METHODS: In the learned helplessness test (LH), Neu-P11 or melatonin (25-100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for 5 days and the number of escape failures and intertrial crossings during the test phase were recorded. In the forced swimming test (FST), rats received a single or repeated administration of Neu-P11 (25-100 mg/kg, ip). The total period of immobility during the test phase was assessed. In the elevated plus-maze test (EPM), mice were treated with Neu-P11 (25-100 mg/kg, ip) or melatonin in the morning or in the evening and tested 2 h later. The percentage of time spent in the open arms and the open arms entries were assessed. RESULTS: In the LH test, Neu-P11 but not melatonin significantly decreased the escape deficit and had no effect on the intertrial crossings. In the FST, a single or repeated administration of Neu-P11, either in the morning or in the evening, significantly decreased the duration of immobility. In the EPM test, Neu-P11 significantly increased the percentage of time spent in the open arms and the open arms entries irrespective to the time of administration. Melatonin was effective only when administered in the afternoon. CONCLUSION: The results demonstrate that Neu-P11 exerts antidepressant and anxiolytic activities in rodent models. PMID- 20581850 TI - Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells. AB - AIM: To investigate the effects of trans-cinnamaldehyde (TCA) on the human leukemia K562 cell line and the cytotoxicity of cytokine-induced killer (CIK) cells against K562 cells. METHODS: Apoptosis, Fas expression, and mitochondrial transmembrane potential in K652 cells were analyzed using flow cytometry. K562 cells were labeled with CFSE. The cytotoxic effect of expanded CIK cells on CFSE labeled K562 cells was determined by FACS flow cytometry. RESULTS: Treatment with TCA 180 micromol/L for 9 h induced apoptosis in 8.9%+/-1.23% of K562 cells. Treatment with 120 or 180 micromol/L TCA for 24 h significantly increased the apoptotic cells to 18.63%+/-1.42 % and 38.98%+/-2.74%, respectively. TCA significantly upregulates Fas expression and decreases mitochondrial transmembrane potential in K562 cells. TCA treatment at 120 and 180 micromol/L for 9 h enhanced the percentage of lysis of K562 cells by expanded CIK cells from 34.84%+/-2.13% to 48.21%+/-2.22 % and 64.81%+/-3.22% at the E:F ratio of 25:1 and from 49.26%+/-3.22% to 57.81%+/-5.13% and 73.36%+/-5.98% at E:F ratio of 50:1. CONCLUSION: TCA exerts cytotoxic effects on human leukemia K562 cells by inducing apoptosis and synergizing the cytotoxicity of CIK cells against K562 cells. These properties of TCA are beneficial to the treatment of leukemia, even in the patients who have received hematopoietic stem cells transplantation (HSCT). PMID- 20581851 TI - Exploring epistatic relationships of NO biosynthesis pathway genes in susceptibility to CHD. AB - AIM: To assess the epistatic relationships of nitric oxide (NO) biosynthesis pathway genes in susceptibility to coronary heart disease (CHD). METHODS: A total of 2142 subjects enrolled in two case-control studies was genotyped for 7 single nucleotide polymorphisms (SNP) within NO biosynthesis pathway genes using TaqMan assays. The association analyses were performed at both SNP and haplotype levels. Two-way SNP-SNP interactions and high-order interactions were tested using multiple unconditional logistic regression analyses and generalized multifactor dimensionality reduction (GMDR) analyses, respectively. RESULTS: Two alleles (rs1049255*C and rs841*A) were identified that were significantly associated with increased risk of CHD after adjusting for all confounders (OR=1.21, 95% CI: 1.06 1.39, combined P=0.001, P(corr)=0.007 and OR=1.30, 95% CI 1.12-1.50, combined P<0.001, P(corr)<0.001, respectively). Significant two-way SNP-SNP interactions were found between SNP rs2297518 and these two significant polymorphisms, affecting the risk of CHD (P<0.001 for both). No significant high-order interactions were identified. CONCLUSION: The results suggested that two-way SNP SNP interactions of polymorphisms within NO biosynthesis pathway genes contribute to CHD risk. PMID- 20581852 TI - Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro. AB - AIM: To examine the inhibitory effects of adenosine monophosphate-activated protein kinase (AMPK) activation on cardiac hypertrophy in vitro and to investigate the underlying molecular mechanisms. METHODS: Cultured neonatal rat cardiomyocytes were treated with the specific AMPK activator 5-aminoimidazole-4 carboxamide ribonucleoside (AICAR) and the specific AMPK antagonist Compound C, and then stimulated with phenylephrine (PE). The Muscle RING finger 1 (MuRF1) small interfering RNA (siRNA) was transfected into cardiomyocytes using Lipofectamine 2000. The surface area of cultured cardiomyocytes was measured using planimetry. The protein degradation was determined using high performance liquid chromatography (HPLC). The expression of beta-myosin heavy chain (beta MHC) and MuRF1, as well as the phosphorylation levels of AMPK and Forkhead box O 1 (FOXO1), were separately measured using Western blot or real-time polymerase chain reaction. RESULTS: Activation of AMPK by AICAR 0.5 mmol/L inhibited PE induced increase in cardiomyocyte area and beta-MHC protein expression and PE induced decrease in protein degradation. Furthermore, AMPK activation increased the activity of transcription factor FOXO1 and up-regulated downstream atrogene MuRF1 mRNA and protein expression. Treatment of hypertrophied cardiomyocytes with Compound C 1 micromol/L blunted the effects of AMPK on cardiomyocyte hypertrophy and changes to the FOXO1/MuRF1 pathway. The effects of AICAR on cardiomyocyte hypertrophy were also blocked after MuRF1 was silenced by transfection of cardiomyocytes with MuRF1-siRNA. CONCLUSION: The present study demonstrates that AMPK activation attenuates cardiomyocyte hypertrophy by modulating the atrophy related FOXO1/MuRF1 signaling pathway in vitro. PMID- 20581853 TI - Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-kappaB pathway in primary rat microglia. AB - AIM: To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia. METHODS: Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 microg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and monocyte chemoattractant protein (MCP-1) was measured with ELISA. Protein expression of the nuclear factor-kappaB (NF-kappaB) p65 subunit, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was detected with immunocytochemistry 1 h or 24 h after LPS treatment. RESULTS: LIG showed a concentration-dependent anti-inflammatory effect in LPS-activated microglia, without causing cytotoxicity. Pretreatment with LIG at 2.5, 5, 10, and 20 micromol/L decreased LPS-induced NO production to 75.9%, 54.4%, 43.1%, and 47.6% (P<0.05 or P< 0.01), TNF-alpha content to 86.2%, 68.3%, 40.1%, and 39.9% (P<0.01, with the exception of 86.2% for 2.5 micromol/L LIG), IL-1beta content to 31.5%, 27.7%, 0.6%, and 0% (P<0.01), and MCP-1 content to 84.4%, 50.3%, 45.1%, and 42.2% (P<0.05 or P<0.01), respectively, compared with LPS treatment alone. LIG (10 micromol/L) significantly inhibited LPS-stimulated immunoreactivity of activated NF-kappaB, COX-2, and iNOS (P<0.01 vs LPS group). CONCLUSION: LIG exerted a potent anti-inflammatory effect on microglia through inhibition of NF kappaB pathway. The data provide direct evidence of the neuroprotective effects of LIG and the potential application of LIG for the treatment of the neuroinflammatory diseases characterized by excessive microglial activation. PMID- 20581854 TI - Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling. AB - AIM: To investigate the protective effects of octacosanol in 6-hydroxydopamine induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins. METHODS: Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD. RESULTS: Oral administration of octacosanol (35-70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway. CONCLUSION: The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment. PMID- 20581855 TI - Angiopoiesis and bone regeneration via co-expression of the hVEGF and hBMP genes from an adeno-associated viral vector in vitro and in vivo. AB - AIM: To investigate the therapeutic potential of adeno-associated virus (AAV) mediated expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP). METHODS: Four experimental groups were administered the following AAV vector constructs: rAAV-hVEGF(165)-internal ribosome entry site (IRES)-hBMP-7 (AAV-VEGF/BMP), rAAV-hVEGF(165)-GFP (AAV-VEGF), rAAV-hBMP-7-GFP (AAV-BMP), and rAAV-IRES-GFP (AAV-GFP). VEGF(165) and BMP-7 gene expression was detected using RT-PCR. The VEGF(165) and BMP-7 protein expression was determined by Western blotting and ELISA. The rabbit ischemic hind limb model was adopted and rAAV was administered intramuscularly into the ischemic limb. RESULTS: Rabbit bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and infected with the four viral vectors. The expression of GFP increased from the 7th day of infection and could be detected on the 28th day post-infection. In the AAV VEGF/BMP group, the levels of VEGF165 and BMP-7 increased with prolonged infection time. The VEGF(165) and BMP-7 secreted from BMSCs in the AAV-VEGF/BMP group enhanced HUVEC tube formation and resulted in a stronger osteogenic ability, respectively. In rabbit ischemic hind limb model, GFP expression increased from the 4th week and could be detected at 8 weeks post-injection. The rAAV vector had superior gene expressing activity. Eight weeks after gene transfer, the mean blood flow was significantly higher in the AAV-VEGF/BMP group. Orthotopic ossification was radiographically evident, and capillary growth and calcium deposits were obvious in this group. CONCLUSION: AAV-mediated VEGF and BMP gene transfer stimulates angiogenesis and bone regeneration and may be a new therapeutic technique for the treatment of avascular necrosis of the femoral head (ANFH). PMID- 20581856 TI - Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes. AB - AIM: To assess the roles of extracellular signal-regulated kinase (ERK), p38, and CD151-integrin complexes on proliferation, migration, and tube formation activities of CD151-induced human umbilical vein endothelial cells (HUVECs). METHODS: CD151, anti-CD151 and CD151-AAA mutant were inserted into recombinant adeno-associated virus (rAAV) vectors and used to transfect HUVECs. After transfection, the expression of CD151 was measured. Proliferation was assessed using the 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell migration was evaluated in Boyden transwell chambers using FBS as the chemotactic stimulus. The tube formation assay was performed on matrigel. The potential involvement of various signaling pathways was explored using selective inhibitors. RESULTS: CD151 gene delivery increased the expression of CD151 at both the mRNA and protein levels. Overexpression of CD151 promoted cell proliferation, migration and tube formation in vitro, and phosphorylation of ERK was also increased. Further, CD151-induced cell proliferation, migration, and tube formation were attenuated by the ERK inhibitor PD98059 (20 micromol/L) but not by a p38 inhibitor (SB203580, 20 micromol/L). Moreover, there was no significant difference in CD151 protein expression between the CD151 group and the CD151-AAA group, but the CD151-AAA mutant abrogated cellular proliferation, migration, and tube formation and decreased the phosphorylation of ERK. CONCLUSION: This study suggests that activation of the ERK signaling pathway may be involved in the angiogenic effects of CD151. Activation of ERK was dependent on the formation of CD151-integrin complexes. Therefore modulation of CD151 may be as a novel therapeutic strategy for regulating angiogenesis. PMID- 20581857 TI - Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen independent prostate cancer PC3 cells. AB - AIM: To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel. METHODS: A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3'UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot. RESULTS: A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC(50) values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells. CONCLUSION: Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment. PMID- 20581858 TI - Mast cell degranulation induced by chlorogenic acid. AB - AIM: To investigate the mechanism of chlorogenic acid (CA)-induced anaphylactoid reactions. METHODS: Degranulation of peritoneal mast cells was assayed by using alcian blue staining in guinea pigs, and the degranulation index (DI) was calculated. CA-induced degranulation of RBL-2H3 cells was also observed and assayed using light microscopy, transmission electron microscopy, flow cytometry, and beta-hexosaminidase release. RESULTS: CA 0.2, 1.0, and 5.0 mmol/L was able to promote degranulation of peritoneal mast cells in guinea pigs in vitro, but it did not increase the degranulation of peritoneal mast cells in CA-sensitized guinea pigs compared with control (P>0.05). Treatment with CA 0.2, 1.0, and 5.0 mmol/L for 30, 60, and 120 min induced degranulation in RBL-2H3 cells in a dose- and time-dependent manner (P<0.01). Under transmission electron microscope typical characteristics of degranulation, including migration of granular vesicles toward the plasma membrane and integration combined with exocytosis, were observed, after CA or C48/80 treatment. Fluorescent microscopy and flow cytometric analysis showed that CA induced concentration-dependent translocation of phosphatidylserine in RBL-2H3 cells. beta-hexosaminidase release in RBL-2H3 cells was significantly increased after incubation with 1 mmol/L CA for 60 min and 5 mmol/L CA for 30 min (P<0.01). CONCLUSION: CA induces degranulation of peritoneal mast cells and RBL-2H3 cells in guinea pigs, which might be one of the mechanisms of the generation of anaphylactoid reactions induced by CA. PMID- 20581859 TI - Bacterial polymers: biosynthesis, modifications and applications. AB - Bacteria can synthesize a wide range of biopolymers that serve diverse biological functions and have material properties suitable for numerous industrial and medical applications. A better understanding of the fundamental processes involved in polymer biosynthesis and the regulation of these processes has created the foundation for metabolic- and protein-engineering approaches to improve economic-production efficiency and to produce tailor-made polymers with highly applicable material properties. Here, I summarize the key aspects of bacterial biopolymer production and highlight how a better understanding of polymer biosynthesis and material properties can lead to increased use of bacterial biopolymers as valuable renewable products. PMID- 20581860 TI - Crosstalk between leukemia-associated proteins MOZ and MLL regulates HOX gene expression in human cord blood CD34+ cells. AB - MOZ and MLL, encoding a histone acetyltransferase (HAT) and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. In MOZ (MOnocytic leukemia Zinc-finger protein)/CBP- or mixed lineage leukemia (MLL) rearranged leukemias, abnormal levels of HOX transcription factors have been found to be critical for leukemogenesis. We show that MOZ and MLL cooperate to regulate these key genes in human cord blood CD34+ cells. These chromatin modifying enzymes interact, colocalize and functionally cooperate, and both are recruited to multiple HOX promoters. We also found that WDR5, an adaptor protein essential for lysine 4 trimethylation of histone H3 (H3K4me3) by MLL, colocalizes and interacts with MOZ. We detected the binding of the HAT MOZ to H3K4me3, thus linking histone methylation to acetylation. In CD34+ cells, depletion of MLL causes release of MOZ from HOX promoters, which is correlated to defective histone activation marks, leading to repression of HOX gene expression and alteration of commitment of CD34+ cells into myeloid progenitors. Thus, our results unveil the role of the interaction between MOZ and MLL in CD34+ cells in which both proteins have a critical role in hematopoietic cell-fate decision, suggesting a new molecular mechanism by which MOZ or MLL deregulation leads to leukemogenesis. PMID- 20581861 TI - Activating transcription factor 2 (ATF2) controls tolfenamic acid-induced ATF3 expression via MAP kinase pathways. AB - Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug associated with anti-tumorigenic and pro-apoptotic properties in animal and in vitro models of cancer. However, the underlying cellular mechanisms by which TA exerts its effects are only partially understood. Activating transcription factor 3 (ATF3) is a member of the ATF/CREB subfamily of the basic region-leucine zipper family and has been known as a tumor suppressor in human colorectal cancer cells. The present study was performed to observe whether ATF3 mediates TA-induced apoptosis and to elucidate the molecular mechanism of ATF3 transcription induced by TA. TA treatment and ectopic expression of ATF3 increased apoptosis, whereas knockdown of ATF3 resulted in significant repression of TA-activated apoptosis. The TA treatment also induced ATF3 promoter activity. Internal deletion and point mutation of the predicted ATF/C/EBP binding site in ATF3 promoter abolished luciferase activation by TA. Overexpression of ATF2 resulted in significant increase in ATF3 promoter activity, and electrophoretic mobility shift assay identified this region as a core sequence to which ATF2 binds. TA treatment resulted in an increase in ATF2 phosphorylation, which was followed by a subsequent increase in ATF3 transcription. Knock down of ATF2 abolished TA induced ATF3 expression. We further provide evidence that TA leads to increases in phospho-p38 MAPK, JNK and ERK levels. Inhibition of these pathways using selective inhibitors and dominant negative constructs ameliorated TA-induced ATF3 expression and promoter activities. The current study shows that TA stimulates ATF3 expression and subsequently induces apoptosis. These pathways are mediated through phosphorylation of ATF2, which is mediated by p38 MAPK-, JNK- and ERK dependent pathways. PMID- 20581862 TI - AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to epithelial transdifferentiation by inhibiting TGF-beta-mediated ERK signaling. AB - Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-beta (TGF-beta) signaling leads to aggressive cancer progression. In this study, we identified zinc-alpha2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation. In vitro, ZAG silencing strikingly increased invasiveness of pancreatic cancer cells accompanied by the induction of a mesenchymal phenotype. Expression analysis of a set of EMT markers showed an increase in the expression of mesenchymal markers (vimentin (VIM) and integrin-alpha5) and a concomitant reduction in the expression of epithelial markers (cadherin 1 (CDH1), desmoplakin and keratin-19). Blockade of endogenous TGF-beta signaling inhibited these morphological changes and the downregulation of CDH1, as elicited by ZAG silencing. In a ZAG-negative cell line, human recombinant ZAG (rZAG) specifically inhibited exogenous TGF-beta-mediated tumor cell invasion and VIM expression. Furthermore, rZAG blocked TGF-beta-mediated ERK2 phosphorylation. PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals. Thus, epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype. PMID- 20581863 TI - Dichotomy in NF-kappaB signaling and chemoresistance in immunoglobulin variable heavy-chain-mutated versus unmutated CLL cells upon CD40/TLR9 triggering. AB - Chronic lymphocytic leukemia (CLL) cells circulating in peripheral blood (PB) differ from the leukemic fraction in lymph nodes (LNs) with respect to cell division and drug sensitivity. CD40 stimulation of PB CLL cells in vitro results in chemoresistance and provides a partial model for the LN microenvironment. The TLR9 ligand CpG induces proliferation in immunoglobulin variable heavy-chain unmutated CLL, but apoptosis in immunoglobulin variable heavy-chain-mutated CLL. To juxtapose proliferative with antiapoptotic signals, we investigated the effects of CpG in the context of CD40 ligation in mutated versus unmutated CLL cells in this study. Prolonged CD40 ligation induced classical, followed by alternative nuclear factor-kappaB (NF-kappaB), activity in both subgroups, correlating with enhanced Bfl-1 and Bcl-X(L) levels, respectively. A dichotomy in NF-kappaB signaling occurred on combined CD40/TLR9 triggering. This induced declining p52 and Bcl-X(L) levels, and reversed chemoresistance only in mutated cells, whereas unmutated cells proliferated, maintained p52 and Bcl-X(L) and remained chemoresistant. The pivotal contribution of Bcl-X(L) to chemoresistance was shown by the BH3 mimetic ABT-737 and RNA interference. Finally, in ex vivo LN samples, p52, p65 and Bcl-X(L) levels were highly expressed, corroborating the in vitro findings. Thus, a distinction in NF-kappaB activation and drug susceptibility in mutated versus unmutated (LN-like) CLL cells was uncovered, which was causally linked to Bcl-X(L) levels. PMID- 20581864 TI - F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death. AB - The c-Abl tyrosine kinase maintains cellular homeostasis through its ability to regulate apoptosis and actin dynamics. In vivo, c-Abl activity is stringently regulated and mechanisms involved are not fully understood. Here, we identified the Rap1 guanine nucleotide exchange factor, C3G (RapGEF1), as a substrate and an effector of c-Abl-mediated functions. Ectopic expression of c-Abl in mammalian cell lines, known to induce apoptosis, resulted in phosphorylation of endogenous C3G on Y504 coincident with cell detachment and chromatin condensation. Phosphorylation of C3G coincided with restricted c-Abl activation in regions rich in actin, and was dependent on cellular F-actin dynamics. Unlike C3G or c-Abl, p C3G was resistant to detergent extraction, suggesting its enhanced affinity for the cytoskeleton. Localized C3G phosphorylation and coincidence with cells undergoing cell death was dependent on F-actin-binding domain (FABD) of c-Abl. Activation of endogenous c-Abl by oxidative stress was associated with phosphorylation of cellular C3G on Y504. Inhibition of C3G expression and function using RNAi or dominant-negative approaches inhibited c-Abl-mediated cell death. These findings identify C3G as a novel target of c-Abl and also show that FABD of c-Abl is essential for regulation of its restricted activation to induce apoptosis. PMID- 20581866 TI - Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers. AB - Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation. PMID- 20581865 TI - The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2. AB - Centrosome amplification (CA) contributes to carcinogenesis by generating aneuploidy. Elevated frequencies of CA in most benign breast lesions and primary tumors suggest a causative role for CA in breast cancers. Clearly, identifying which and how altered signal transduction pathways contribute to CA is crucial to breast cancer control. Although a causative and cooperative role for c-Myc and Ras in mammary tumorigenesis is well documented, their ability to generate CA during mammary tumor initiation remains unexplored. To answer that question, K Ras(G12D) and c-Myc were induced in mouse mammary glands. Although CA was observed in mammary tumors initiated by c-Myc or K-Ras(G12D), it was detected only in premalignant mammary lesions expressing K-Ras(G12D). CA, both in vivo and in vitro, was associated with increased expression of the centrosome-regulatory proteins, cyclin D1 and Nek2. Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced CA, whereas silencing cyclin E1 or B2 had no effect. Thus, we conclude that CA precedes mammary tumorigenesis, and interfering with centrosome regulatory targets suppresses CA. PMID- 20581867 TI - H1047R phosphatidylinositol 3-kinase mutant enhances HER2-mediated transformation by heregulin production and activation of HER3. AB - Hyperactivation of phosphatidylinositol-3 kinase (PI3K) can occur as a result of somatic mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K. The HER2 oncogene is amplified in 25% of all breast cancers and some of these tumors also harbor PIK3CA mutations. We examined mechanisms by which mutant PI3K can enhance transformation and confer resistance to HER2-directed therapies. We introduced the PI3K mutations E545K and H1047R in MCF10A human mammary epithelial cells that also overexpress HER2. Both mutants conferred a gain of function to MCF10A/HER2 cells. Expression of H1047R PI3K, but not E545K PI3K, markedly upregulated the HER3/HER4 ligand heregulin (HRG). HRG siRNA inhibited growth of H1047R but not E545K-expressing cells and synergized with the HER2 inhibitors trastuzumab and lapatinib. The PI3K inhibitor BEZ235 markedly inhibited HRG and pAKT levels and, in combination with lapatinib, completely inhibited growth of cells expressing H1047R PI3K. These observations suggest that PI3K mutants enhance HER2-mediated transformation by amplifying the ligand-induced signaling output of the ErbB network. This also counteracts the full effect of therapeutic inhibitors of HER2. These data also suggest that mammary tumors that contain both HER2 gene amplification and PIK3CA mutations should be treated with a combination of HER2 and PI3K inhibitors. PMID- 20581868 TI - Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas. AB - Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low-oxygen culture conditions and in clinical specimens of both low- and high-grade tumors. The observed global checkpoint signaling, in contrast to only focal areas of overabundant p53 (indicative of p53 mutation) in grade II astrocytomas, are consistent with DDR activation being an early event in gliomagenesis, initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression. Overall, these results support the potential role of the DDR machinery as a barrier to gliomagenesis and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development. PMID- 20581869 TI - Genomic analysis of genetic heterogeneity and evolution in high-grade serous ovarian carcinoma. AB - Resistance to chemotherapy in ovarian cancer is poorly understood. Evolutionary models of cancer predict that, following treatment, resistance emerges either because of outgrowth of an intrinsically resistant sub-clone or evolves in residual disease under the selective pressure of treatment. To investigate genetic evolution in high-grade serous (HGS) ovarian cancers, we first analysed cell line series derived from three cases of HGS carcinoma before and after platinum resistance had developed (PEO1, PEO4 and PEO6; PEA1 and PEA2; and PEO14 and PEO23). Analysis with 24-colour fluorescence in situ hybridisation and single nucleotide polymorphism (SNP) array comparative genomic hybridisation (CGH) showed mutually exclusive endoreduplication and loss of heterozygosity events in clones present at different time points in the same individual. This implies that platinum-sensitive and -resistant disease was not linearly related, but shared a common ancestor at an early stage of tumour development. Array CGH analysis of six paired pre- and post-neoadjuvant treatment HGS samples from the CTCR-OV01 clinical study did not show extensive copy number differences, suggesting that one clone was strongly dominant at presentation. These data show that cisplatin resistance in HGS carcinoma develops from pre-existing minor clones but that enrichment for these clones is not apparent during short-term chemotherapy treatment. PMID- 20581871 TI - Transcriptional factor HBP1 targets P16(INK4A), upregulating its expression and consequently is involved in Ras-induced premature senescence. AB - Oncogene-mediated premature senescence has emerged as a potential tumor suppressive mechanism in early cancer transitions. Many studies showed that Ras and p38 mitogen-activated protein kinase (MAPK) participate in premature senescence. Our previous work indicated that the HMG box-containing protein 1 (HBP1) transcription factor is involved in Ras- and p38 MAPK-induced premature senescence, but the mechanism of which has not yet been identified. Here, we showed that the p16(INK4A) cyclin-dependent kinase inhibitor is a novel target of HBP1 participating in Ras-induced premature senescence. The promoter of the p16(INK4A) gene contains an HBP1-binding site at position -426 to -433 bp from the transcriptional start site. HBP1 regulates the expression of the endogenous p16(INK4A) gene through direct sequence-specific binding. With HBP1 expression and the subsequent increase of p16(INK4A) gene expression, Ras induces premature senescence in primary cells. The data suggest a model in which Ras and p38 MAPK signaling engage HBP1 and p16(INK4A) to trigger premature senescence. In addition, we report that HBP1 knockdown is also required for Ras-induced transformation. All the data indicate that the mechanism of HBP1-mediated transcriptional regulation is important for not only premature senescence but also tumorigenesis. PMID- 20581872 TI - On beyond GWAS. AB - Analyses of genome-wide association studies (GWAS) show that common SNPs can account for the majority of the heritability of complex traits, but that there are likely to be limits to the usefulness of the current strategy of accumulating common variants of small effect for risk prediction. The ongoing success of GWAS has implications for functional characterization of trait-associated loci. PMID- 20581870 TI - From smoking to lung cancer: the CHRNA5/A3/B4 connection. AB - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that modulate key physiological processes ranging from neurotransmission to cancer signaling. These receptors are activated by the neurotransmitter, acetylcholine, and the tobacco alkaloid, nicotine. Recently, the gene cluster encoding the alpha3, alpha5 and beta4 nAChR subunits received heightened interest after a succession of linkage analyses and association studies identified multiple single nucleotide polymorphisms in these genes that are associated with an increased risk for nicotine dependence and lung cancer. It is not clear whether the risk for lung cancer is direct or an effect of nicotine dependence, as evidence for both scenarios exist. In this study, we summarize the body of work implicating nAChRs in the pathogenesis of lung cancer, with special focus on the clustered nAChR subunits and their emerging role in this disease state. PMID- 20581873 TI - Associations of CFHR1-CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent. PMID- 20581875 TI - Limits of sequence and functional conservation. AB - Sequence conservation of noncoding DNA across species can indicate functional conservation. However, a new study demonstrates notable differences between human and mouse stem cell regulatory networks, suggesting caution in generalizing from sequence to functional conservation. PMID- 20581876 TI - Hints of hidden heritability in GWAS. AB - Although susceptibility loci identified through genome-wide association studies (GWAS) typically explain only a small proportion of the heritability, a classical quantitative genetic analysis now argues that considering together all common SNPs can explain a large proportion of the heritability of these complex traits. A related study provides recommendations for the sample sizes needed in future GWAS to identify additional susceptibility loci. PMID- 20581877 TI - Fungal pathogenicity and morphological switches. AB - The virulence of Candida albicans, a major human fungal pathogen, has been considered dependent on the ability to transition between different morphologies. A new study reports a screen of C. albicans mutants that demonstrates that pathogenesis can be dissociated from morphological switching and in vitro growth rate. PMID- 20581879 TI - Prospective comparison of PCR-based vs late mRNA-based preemptive antiviral therapy for HCMV infection in patients after allo-SCT. AB - Human CMV (HCMV)-directed preemptive therapy has helped to improve the outcome following allo-SCT. In this study, we evaluated the safety and efficacy of a late mRNA-based (NucliSens CMV pp67) anti-HCMV treatment strategy. A prospective randomized multicenter pilot trial was performed comparing PCR-based, with late mRNA-based preemptive HCMV-directed antiviral therapy in patients after allo-SCT. In all, 133 patients were randomized in three different centers at the time of transplant, 130 of whom are evaluable. Viral screening was performed weekly. Antiviral therapy was initiated at the second consecutive positive PCR result, or at the first detection of late mRNA. The therapy was stopped if clearance of HCMV DNA or late mRNA was demonstrated after 14 days of antiviral therapy. If HCMV infection persisted, antiviral therapy was continued in a reduced dose. The median duration of antiviral therapy during the first treatment episode was 28 days for PCR-, and 19 days for mRNA-screened patients (P<0.02). However, the overall duration of antiviral therapy, as well as the incidence of HCMV disease and the OS at day 100 after transplantation was comparable between the two study groups. We conclude that late mRNA-based anti-HCMV therapy may show comparable safety and efficacy with PCR-based therapy in patients after allo-SCT. PMID- 20581881 TI - Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I. AB - Type I diabetes mellitus is a metabolic disease caused by chronic immune attack against the insulin-producing cells of the pancreas. It has recently been shown that the clinical course of this disease can be interrupted by immune ablation and PBSCT. In this report, we describe our experience with this treatment modality in a series of eight cases. Patients with newly diagnosed type I diabetes were received treatment consisting of two to three plasmaphereses, hematopoietic stem cell mobilization with CY and G-CSF, collection of at least 3 * 10(6) per kg of CD34+ cells, and conditioning with CY and anti-thymocyte globulin followed by stem cell infusion. All patients became independent of exogenous insulin after the transplantation. One patient resumed low-dose insulin 7 months after transplantation. Six out of eight patients were given acarbose for better glycemic control after transplantation. All patients exhibited good glycemic control: the average HbA1c concentrations were 12.3% at diagnosis, and 5.6 and 6.2% at 3 and 6 months after transplantation, respectively. We conclude that at least temporary independence of exogenous insulin can be achieved in type I diabetes patients following immunoablation and reconstitution of the immune system with autologous PBSCs. PMID- 20581880 TI - Treatment of Fanconi anemia patients using fludarabine and low-dose TBI, followed by unrelated donor hematopoietic cell transplantation. AB - A nonmyeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy TBI has been used extensively and with substantial engraftment success without promoting excessive nonrelapse mortality in medically infirm patients requiring hematopoietic cell transplantation. In this paper, we studied this same low toxicity regimen as a means of promoting engraftment of unrelated donor hematopoietic cell transplantation in patients with Fanconi anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicities. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic GVHD occurred in four and three patients, respectively. Three patients are alive and well at a median of 45.9 (range, 20.9-68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSCs, but is associated with significant chronic GVHD. PMID- 20581882 TI - Pericardial effusion post-SCT in pediatric recipients with signs and/or symptoms of cardiac disease. AB - The objective of this study was to assess the incidence, risk factors, outcome and impact on OS of pericardial effusion (PEF) in a cohort of 156 pediatric SCT recipients. The mean age was 8.15+/-6.25 years. In all, 74% of the patients had malignant disease and 35% of the patients received autologous stem cell grafts. Twenty-three subjects developed effusion at 2.75+/-3.54 months after SCT. The overall probability of developing a PEF after SCT was 16.9%. In the multivariate analysis of risk factors associated with time to PEF, increased age, allogeneic risk status and conditioning type, were all significant factors. In a multivariate analysis of time to death, PEF, CMV status and risk status were all independent risk factors. PEF, however, had the highest HR of 3.334. Of the 23 patients with PEF, 19 died (82.6%); however, none died as a direct result of pericardial tamponade. In summary, our results suggest that PEF is a significant risk factor for post transplant mortality. These results suggest a need for more frequent evaluation and monitoring for development of PEF. Studies are needed to determine the etiology of, and new therapeutic strategies for, PEF in the post SCT population. PMID- 20581883 TI - What is the upper age limit for performing allo-SCT? Cord blood transplantation for an 82-year-old patient with AML. PMID- 20581884 TI - Cryptosporidium parvum infection vs GVHD after hematopoietic SCT: diagnosis by PCR with resolution of symptoms. PMID- 20581885 TI - Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. AB - Extracorporeal photopheresis (ECP) has been shown to be a promising treatment for chronic graft-versus-host disease; however, only a few case reports are available that examine the effectiveness of ECP for bronchiolitis obliterans (BO) after allo-SCT. Because of the poor response to traditional therapies, ECP has been explored as a possible therapeutic option for severe BO after allo-SCT. Nine patients received ECP between July 2008 and August 2009 after a median follow-up of 23 months (range 9-93 months) post transplant. The primary indication for ECP was the development of BO in patients who had failed prior multidrug regimens. The median number of drugs used for BO management before ECP was 5 (range 2-7); this included immunosuppressive therapy. Six of nine (67%) patients responded to ECP after a median of 25 days (range 20-958 days). No ECP-related complications occurred. ECP seemed to stabilize rapidly declining pulmonary function tests in about two-thirds of patients with severe and heavily pretreated BO that developed after allo-SCT. This finding supports the need for a larger prospective study to confirm the impact of ECP on BO, and to consider earlier intervention with ECP to improve the outcome of BO after allo-SCT. PMID- 20581886 TI - Retrospective analysis of treosulfan-based conditioning in comparison with standard conditioning in patients with myelodysplastic syndrome. AB - Myelodysplastic syndromes (MDSs) often occur in older adults with significant comorbidities. Therefore, a reduced-toxicity conditioning regimen may be more suitable than standard conditioning regimens before allogeneic blood stem cell transplantation. Here, we retrospectively compare the outcome of a treosulfan based conditioning regimen with standard myeloablative TBI-based conditioning regimens in patients (pts) with MDS. A total of 48 pts with MDS were included in the study, of which 29 (60%) pts received TBI-based and 19 (40%) pts received a treosulfan-based conditioning regimen. A significantly lower relapse incidence (5% vs 34% at 3 years, P=0.019) resulting in a better, but not statistically significant relapse-free survival (RFS) (57% vs 31%, P=0.086) was observed after treosulfan-based conditioning. In pts with increased risk for significant side effects due to comorbidities (haematopoietic stem cell transplantation specific comorbidity index), the estimated 3-year RFS was significantly better in the treosulfan group: 54% (95% confidence interval (CI), 17-90%) compared with pts in the TBI group: 11% (95% CI, 0-44%; log-rank test P=0.0455). Treosulfan-based conditioning therapy is a feasible and effective regimen for pts with MDS, especially in pts with preexisting comorbidities. PMID- 20581888 TI - Multiple myeloma with concomitant JAK2-positive essential thrombocythemia post successful autologous peripheral blood hematopoietic stem cell transplant. PMID- 20581887 TI - Phase II trial of high-dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma. AB - In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received topotecan 3.5 mg/m(2) intravenously on days -6 to -2, melphalan 70 mg/m(2) intravenously on days -3 and -2 and CY 1 g/m(2) intravenously on days -6, -5 and -4. Overall response rate (ORR) consisting of complete response and partial response (CR+PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45-72) were enrolled. Forty-one patients were treated for consolidation of first remission, while 19 patients had relapsed/refractory disease. ORR was 85% (CR 12%, very good PR 43% and PR 30%). Median time to neutrophil (ANC>0.5 * 10(9)/L) and plt engraftment (>20 * 10(9)/L) was 10 (range 7-12 days) and 9 days (range 6-79 days), respectively. A majority of the common adverse events were grade 1-3 mucositis/stomatitis (65%), grade 1 or 2 nausea (59%) and grade 1 or 2 diarrhea (41%). Median PFS was 18.5 months and median OS has yet not been reached. In conclusion, topotecan, melphalan and CY is a safe and active conditioning regimen for auto hematopoietic SCT in MM. The ORR and PFS were comparable to high-dose melphalan. PMID- 20581889 TI - Severe to profound hearing loss--are we really managing it in New Zealand? PMID- 20581890 TI - An audit of referrals to the Southern Cochlear Implant Paediatric Programme. AB - AIM: To audit the age at referral and time to assessment and implantation in children presenting to the Southern Cochlear Implant Paediatric Programme and identify any delay in implantation, particularly in individuals with pre-lingual sensorineural hearing loss. METHODS: All paediatric referrals to the Southern Cochlear Implant Programme from March 2003-March 2008 were evaluated retrospectively. The Student t-test was used to compare median time intervals between those with and without risk factors for Sensorineural hearing loss. RESULTS: Seventy five children were referred, 42 with pre-lingual deafness and 33 with post-lingual deafness. The median age of referral was 17 months with a range of 1 to 203 months. Thirty-five children with pre-lingual deafness were accepted as candidates and implanted, 6 were declined as they were too old to receive benefit from cochlear implantation. Of these 6 children who were declined, 4 had not been adequately diagnosed despite having risk factors for sensorineural hearing loss. There was no significant difference in the age of referral in pre lingually deafened children between those with risk factors and those without risk factors. CONCLUSION: The age at referral of pre-lingually deafened children to the Southern Cochlear Implant Programme is unacceptably high, particularly in those children who have known risk factors for sensorineural hearing loss. PMID- 20581891 TI - Trends in the use of minimally invasive surgery in children. AB - AIM: To determine trends in the scope of use of minimally invasive surgical (MIS) techniques in children as a predictor of future operative workload and operating theatre requirements. METHOD: A retrospective review was conducted of all paediatric patients less than 16 years of age who underwent minimally invasive surgical procedures at Christchurch Hospital, New Zealand between 1996 and 2007. RESULTS: There were 1693 children who received 1826 MIS procedures during a period in which 11,893 operative procedures were performed. MI case-weights, an indirect measure of the financial burden and technical difficulty of the procedures, represented 29% of the workload of the unit overall. There was a rapid rise of the number of MIS procedures from 1996 to 2000, but since then the scope and volume has changed little. CONCLUSION: Use of MIS in children increased rapidly until 2000 since which time it has remained relatively constant. Recent additional applications have involved a small number of rare low-volume and more complex procedures. These observations may assist in the planning of theatre allocation requirements for MIS in children. PMID- 20581892 TI - Juvenile thyrotoxicosis--a South Island, New Zealand experience with long-term outcome. AB - AIM: To assess our experience in the management of juvenile thyrotoxicosis. METHOD: Retrospective review of thyroid clinic records of juvenile (<16 y) thyrotoxic (JT) patients treated at thyroid clinic between 1972 and 1999. Long term (>8 y) treatment outcome was assessed. RESULTS: During the 28-year period, 34 JT patients were diagnosed and treated--30 girls and 4 boys, median age 13 years (5.6-15.9 y). Thirty-two children had Graves' disease and two had toxic nodular goitre. All patients were initially treated with carbimazole, and no major adverse reactions occurred. One Graves' disease child later developed severe ophthalmopathy. During long-term follow-up, 12 of the 32 Graves' patients remain in remission after antithyroid drug treatment alone, but 4 of these 12 patients are currently receiving thyroxine replacement. Fifteen patients were surgically treated (median age 16 y), and six patients received radioiodine therapy (median age 18 y) including one patient with post-thyroidectomy relapse. The two patients with toxic nodular goitre were treated by thyroidectomy. CONCLUSION: Juvenile thyrotoxicosis is relatively rare and not always due to Graves' disease. More than a third of children with Graves' disease achieved long term remission following antithyroid drug therapy, and remaining patients required definitive therapy. PMID- 20581893 TI - The utility of plain radiography in assessment of upper aerodigestive tract fishbone impaction: an evaluation of 22 New Zealand fish species. AB - AIMS: To determine the utility of plain radiography for suspected upper aerodigestive tract fishbone impaction in New Zealand fish species. METHODS: Tissue densities of the least and most dense regions of the upper aerodigestive tract were measured on a lateral soft tissue X-ray of the neck. Densities of the measured regions were reproduced in two custom manufactured radiological phantoms. Epipleural bones from 22 commonly eaten New Zealand fish species were X rayed within these phantoms. Forty-one Emergency Department doctors graded the X ray visibility of each bone using a five point visual analogue scale. RESULTS: Twenty species (90.9%) returned a sensitivity of 95% or greater when viewed within the least dense phantom. The two species with lesser sensitivities within the least dense phantom were Red Cod (90.2%) and Ray's Bream (58.8%). Only one species (Black Cardinalfish; 4.5%) returned a sensitivity of 95% or greater when viewed within the most dense phantom. CONCLUSIONS: Bones from the majority of commonly eaten New Zealand fish species are poorly visible when X-rayed in a background of soft tissue density. Given fishbones frequently impact in regions of high tissue density, plain radiography would appear insufficiently sensitive to exclude upper aerodigestive tract fishbone impaction. PMID- 20581894 TI - Helicobacter pylori infection and iron deficiency in teenage females in New Zealand. AB - BACKGROUND: Iron deficiency is an important problem in New Zealand children and young adults. Iron deficiency and Helicobacter pylori (H. pylori) infection are each more common in Maori and Pacific Island ethnic groups. AIMS: This study seeks to determine if H. pylori infection is associated with iron deficiency. METHODS: 792 female students from 7 Auckland high schools (median age 16 years) had H. pylori serology and tests for iron deficiency assessed by a combination of serum ferritin, iron saturation and mean cell volume. RESULTS: The prevalence of positive H. pylori serology was highest for Pacific Island students (49.0%; CI 38.0-60.0), intermediate for Maori (26.7%; CI 16.9-36.4) and Asian (24.7%; CI 12.6-36.7) and lowest for European (13.7%; 6.0-21.4) p<0.0001. Students with positive H. pylori serology had lower mean levels of iron saturation (p=0.013), but not of ferritin (p=0.068), haemoglobin (p=0.08) or mean cell volume (p=0.16), compared to those with negative serology. Positive H. pylori serology was associated with increased risk of iron deficiency (RR 1.20; CI 1.08-1.34), but not anaemia (RR 1.01; CI 0.87-1.18), after adjusting for age, ethnicity and school SES decile. CONCLUSIONS: This study indicates that H. pylori infection is associated with iron deficiency in adolescent females. There are significant differences in H. pylori serology amongst different ethnic groups in New Zealand. PMID- 20581895 TI - Pertussis continues to put New Zealand's immunisation strategy to the test. AB - Young children in New Zealand remain at an unacceptably high risk of pertussis. As an indicator of child disease burden hospitalisation rates have increased in each decade since the 1960s. Despite improvements over the past 15 years immunisation coverage (77% at age 2 years in 2005) remains lower than the level of about 95% necessary to control pertussis. For global pertussis control, seven strategies beyond the primary infant series and early childhood booster doses are currently recommended: (1) Reinforce and/or improve infant and toddler immunisation strategies; (2) Universal preschool booster doses; (3) Universal adolescent immunisation; (4) Universal adult immunisation; (5) Selective immunisation of new mothers, family, and close contacts of newborns; (6) Selective immunisation of healthcare workers; and (7) Selective immunisation of childcare workers. The first of these--reinforcement and/or improvement of current infant and toddler immunisation strategies--is the highest priority for New Zealand and would reduce infant pertussis disease burden. The universal preschool booster (age 4 years) and the adolescent (11 year) booster should remain. Because of low coverage and unknown effectiveness for protection of infants routine adult pertussis immunisation is of lower priority. Of the targeted strategies selective immunisation of healthcare workers is necessary to prevent nosocomial spread to vulnerable infants. All staff who work in neonatal units and other clinical settings where there are infants should receive a booster dose of pertussis vaccine. Control of pertussis in New Zealand continues to prove elusive. Improving immunisation coverage and timeliness should remain the primary focus of pertussis control in New Zealand. PMID- 20581896 TI - Current enoxaparin dosing guidelines have dubious credibility. AB - AIM: To assess the prescribing practice of enoxaparin in comparison to dosing guidelines. METHOD: A prospective observational chart review of patients who received enoxaparin for the treatment of thrombosis at Dunedin Public Hospital between August 2007 and January 2008. Deviations in dose from guidelines were defined and recorded along with various clinical and demographic data of participants. RESULTS: Fifty-nine patients (62 admissions) were recruited. Dose deviations occurred on 19 (30.7%) occasions. More dose deviations occurred at or close to guideline transition points (total body weight over 90 kg and/or creatinine clearance between 20-40 mL/min). CONCLUSION: Current enoxaparin dosing guidelines are too simplistic and result in discord between dosing in practice and that approved by Medsafe. PMID- 20581897 TI - Button batteries: the worst case scenario in nasal foreign bodies. AB - AIM: To present four cases of button battery nasal foreign bodies that were referred to an otolaryngology department over a 6-month period. METHODS: Four cases are presented and discussed with a review of current literature. RESULTS: Four children aged 2-4 years who were referred to an otolaryngology department over about 6 months were found to have a button battery in their nose. While there was mucosal damage in all the noses the likelihood of a septal perforation developing appears to be related to the time interval between insertion and removal. The two patients who did not develop a septal perforation had the battery removed after about 90 minutes and 3 days. The two patients who did develop a perforation had the battery removed after 4 hours and 24 hours. Battery thickness may also be important as the patient who had the battery removed at 3 days had a 2 mm thick battery whereas the other three all had a 5 mm thick battery. DISCUSSION: As button batteries are ubiquitous it is imperative that consumers and medical practitioners are aware of the risks they pose if placed in the nose, and also elsewhere in the body. CONCLUSION: As early removal of a button battery is likely to decrease the chances of a septal perforation developing a nasal foreign body should be considered to be a button battery until proven otherwise. PMID- 20581898 TI - Nodular regenerative hyperplasia of the liver secondary to azathioprine in a patient with inflammatory bowel disease. AB - A case of dramatic portal hypertension with massive ascites and splenomegaly is described in a patient with inflammatory bowel disease receiving azathioprine therapy. Liver biopsy confirmed the subtle changes of nodular regenerative hyperplasia and the patient recovered following withdrawal of the azathioprine and commencement of spironolactone. Thrombocytopaenia is an early clue to azathioprine-induced nodular regenerative hyperplasia of the liver. PMID- 20581899 TI - Medical image. Systemic lupus erythematosus (SLE) in a paediatric unit. PMID- 20581900 TI - Why did so many women develop cancer? PMID- 20581901 TI - Simple suggestions to improve New Zealand Ethical Committees. PMID- 20581902 TI - Effect of using the title 'Dr' on perceptions of complementary and alternative medicine. PMID- 20581904 TI - Is evidence-based medicine a sham? PMID- 20581903 TI - Chaos at the cash register. PMID- 20581905 TI - Health-related quality of life and its growing importance in clinical practice. PMID- 20581906 TI - Salt reduction in New Zealand: are we keeping up with Australia? PMID- 20581907 TI - Lessons from complaints: implications for medical education. PMID- 20581908 TI - Realising the research power of complaints data. PMID- 20581909 TI - Opportunities to learn from medical incidents: a review of published reports from the Health and Disability Commissioner. AB - AIMS: To analyse recent published information about the Health and Disability Commissioner's investigations in the context of The New Zealand Medical Council's Domains of Competence and investigate possible relationships. METHODS: Retrospective review of 100 recent Health and Disability Commissioner (HDC) investigations published online (all cases reviewed regardless of the Commissioner's 'verdict'), involving at least one medical practitioner. Breaches and issues raised were categorised according to the Domains of Competence set by the Medical Council of New Zealand. RESULTS: The most common area of competence identified in the HDC investigations was that of Medical Expert, in 92.9% of cases. The second was Communication, identified in 48.7% of cases. Many cases included more than one Domain of Competence, with an average of 1.8 domains per investigation. Further characteristics of the cases were examined and a number of medical practitioner, patient, setting and timing statistics are also presented. CONCLUSIONS: This study finds medical expertise and communication skills to be the key areas of a medical practitioner's role that public complaints address. Beyond this, the limited data available through the Commissioner's published reports make it difficult to draw conclusions which might assist with the improvement of medical practice in New Zealand. We therefore conclude that the data available is useful only at a case-by-case level. More extensive use of published information about incidents involving medical practitioners will have to await changes to provide for the systematic reporting of a much higher proportion of incident investigations. Given New Zealand's current environment for dealing with medical complaints, this may require changes beyond the area of consumer complaint investigations considered here. PMID- 20581910 TI - Sickness presenteeism in a New Zealand hospital. AB - AIMS: The aim of this study was to assess the attitudes of hospital clinical staff to acute personal illness. METHODS: A self-reported questionnaire was developed. Four hundred clinical staff employed by the district health board (DHB) who met the inclusion criteria who were randomly selected. Data were collected and analysed using SPSS software. Ethical approval was obtained from the Lower South Regional Ethics Committee and from the DHB Health Research Office. RESULTS: Doctors were more likely to exhibit sickness presenteeism (SP)- i.e. working despite being sick--than any other occupational group at the DHB. Two main reasons were given for not taking sick leave: staff did not believe they were unwell enough to justify taking leave and they did not want to increase the workload of others. The majority of study participants would not contact anyone for advice about whether to take leave. CONCLUSION: This study provides evidence that SP, especially in doctors, is prevalent in the DHB and is similar to findings from elsewhere. Low rates of clinical staff contacting someone for advice on coming to work whilst ill could be targeted to improve infection control. PMID- 20581911 TI - Towards a reliable and accurate ethnicity database at district and national levels: progress in Canterbury. AB - AIMS: To analyse the extent of ethnicity and related recording in Canterbury primary health organisations (PHOs), to examine variation between general practices and PHOs in ethnicity recording, and to compare the findings with census figures with particular reference to Maori. METHODS: Data for July 2009 from the five Canterbury PHOs were analysed. Totals and rates for different categories of ethnicity were calculated including ethnicity 'not stated'. Differences in rates between general practices for ethnicity 'not stated' were calculated. The results were compared with census figures for different ethnicities. FINDINGS: A total population of 476,042 was analysed of whom 6.2% were Maori and 2.1% Pacific people. 'No ethnicity' was recorded for only 3.4% of the population. This figure varied from 0.4 to 4.5% between PHOs but was much wider between practices. Comparison with census figures showed that 95.4% of the Canterbury district population were enroled. Only 76.4% of Maori were classified as enroled as compared with the census estimates. CONCLUSION: Canterbury PHOs/general practices, along with national PHOs, have reduced ethnicity 'not stated' to almost negligible levels. The difference between the PHO and census figures for Maori is probably due to the different systems used by Statistics New Zealand for the census and for health classifications. Nationally there are now some 102,000 less in the PHO data as compared with census estimates. However the PHO general practice records should now be used to provide an accurate and up-to date district and national database for analysis and funding. In doing so it ensures that calculated morbidity and other rates use an identical denominator and numerator. PMID- 20581912 TI - Distinguishing between tertiary and secondary facilities: a case study of cardiac diagnostic-related groups (DRGs). AB - AIM: To develop a classification of tertiary cardiac DRGs in order to investigate differences in tertiary/secondary product mix across New Zealand district health boards (DHBs). METHOD: 67 DRGs from 85,442 cardiac cases were analysed using cost weights and patient comorbidity complexity levels, which were used as a proxy for complexity. RESULTS: The research found high variability of severity within some DRGs. 5 DHBs are the main providers of 27 DRGs which are high cost and identified as tertiary by several ADHB clinicians; the same 5 DHBs have on average higher severity by DRG than the other DHBs. CONCLUSIONS: NZ tertiary hospitals have a product mix of DRGs with higher complexity than secondary hospitals. Funding based on case weights needs to recognise the additional resource requirements for this higher complexity. PMID- 20581913 TI - Four policies to end the sale of cigarettes and smoking tobacco in New Zealand by 2020. AB - AIM: To phase out sales of cigarettes and of smoking tobacco products in New Zealand by the year 2020. CURRENT SITUATION: 99% of tobacco is smoked as cigarettes. Cigarettes are highly addictive, lethal, and cannot be made safer. Since 1950 commercial cigarettes have prematurely killed over 160,000 New Zealanders. Despite causes-disease warnings on tobacco packaging (from 1987) and graphic warnings (2007), bans on tobacco advertising and promotions (1990), bans on indoor workplace smoking (1990, 2004), subsidies on medicinal nicotine (2000), and despite one-third of smokers annually making serious attempts to quit, 1 in 5 New Zealand adults smoke, 2 in 5 Maori adults smoke, and cigarette consumption per adult remains virtually unchanged since 2003. Four in 5 smokers regret they ever started. PROPOSED POLICIES: Four policies combined could make cigarette smoking less attractive and the use of nicotine-only products more attractive, with respect to relative price, availability and addictiveness. These mean increasing tax on all cigarettes equally; and a bill to strengthen the Smoke-free Environments (SFE) Act: to allot cigarette sales quotas and then gradually lower them; reduce the nicotine content of cigarettes gradually by a sinking lid or by nicotine tax; and permit the sale of satisfying non-combustible nicotine-only products for smokers. As supply reduces, prices rise, and nicotine satisfaction decreases, smokers will quit; and black market risk will be minimised. Commercial cigarettes will no longer be obtainable, and even if some smoke tobacco grown legally for their own use, or even if some is obtainable illegally, tobacco consumption will greatly reduce. CONCLUSION: The smoking of tobacco sold legally kills 5000 New Zealanders annually. The SFE Act can be amended to phase out legal sales within this decade. Intensive policy research is needed now as public interest increases. Support from the public and from legislators to promote a suitable amendment bill is now needed. PMID- 20581914 TI - Measuring the safety culture in a hospital setting: a concept whose time has come? AB - AIM: Getting the right 'patient safety culture' is thought to be an important component in improving patient safety in hospitals, however there is a lack of clarity in how best to measure and improve it, and whether such improvement actually translates to better patient outcomes. This paper reflects on the Counties Manukau District Health Board (CMDHB) experience with a patient safety survey and attempts to answer questions other organisations may ask when deciding whether to invest in such survey. METHODS: A literature search was undertaken to identify valid and reliable patient safety culture survey tools. These were reviewed with respect to how best to interpret and use the results. RESULTS: If hospitals decide to undertake a patient safety culture survey, the recommended survey tools are the Safety Attitudes Questionnaire (SAQ) and the Hospital Survey on Patient Safety (HSOPS). Both have been widely used and have sound and comprehensive psychometrics. Only the SAQ has established links with patient safety outcomes such as reduced healthcare associated infections. CONCLUSION: Surveys can provide some insights into the patient safety culture within an organisation, but the opportunity costs of undertaking a survey should be carefully considered. Much of their value lies in raising the profile of patient safety and promoting conversations; making patient safety 'the way we do business around here'. PMID- 20581915 TI - Building on myths: an economist's response to the Ministerial Review Group Report on the health system. AB - The (2009) Report of the Ministerial Review Group (MRG) recommends a number of useful measures to enhance the New Zealand health system such as reducing the number of primary health organisations (PHOs). However, the report's warnings about the "unsustainability" of the current publicly funded health system are overstated. I argue that the logic for the creation of new agencies and the break up of the functions of the Ministry of Health has not been clearly articulated. Restructuring is an extremely expensive exercise--and should only be done when there is a compelling logic to the new structure. PMID- 20581916 TI - The benefits and risks of DHBs contracting out elective procedures to private providers. AB - A key plank of the New Zealand National Party's health policy is to "Support the smart use of the private sector to increase the number of people getting timely access to vitally needed surgery, and reduce hospital waiting lists". This policy raises a number of questions. These include: How do the two sectors compare with respect to the efficiency of elective surgical services? What effects might increasing private provision have on public hospitals? What impact might the policy have on access to care and equity amongst population groups? What are the effects of different methods of setting prices? This paper reviews both the theory and evidence about these and other questions related to the mix of public and private providers of surgical services in a publicly funded health system. It is concluded that the policy has some potential benefits but also carries a number of risks. If the policy is to be successful, the district health boards (DHBs) will need to be alert to these potential risks and be prepared with strategies to mitigate them. PMID- 20581917 TI - Using information and communications technology to enable the exchange of information between New Zealand clinicians and health providers. AB - AIM: The aim of this paper is to examine the current state of healthcare information exchange in the New Zealand health and disability sector. The paper describes the priorities and main drivers and barriers to creating a free flow of health information in the New Zealand health system. METHOD: The paper draws on findings from extensive research of over 2500 New Zealand clinicians and decision makers conducted from 2007 to 2009 and other references. RESULTS: The research findings support a view that technology-enabled information exchange could significantly improve healthcare delivery processes and enable person-centred care initiatives. Three-quarters of clinicians surveyed agreed that better electronic access to healthcare information could improve the way they provided health services. The research suggests that the greatest potential for benefit in the sector is in improving the capability to electronically exchange test results, patient referrals, discharge summaries, and medication information. While there is widespread support for improving health information communication technology, there is also a strong belief that a lack of compatible systems, as well as the need for increased funding, are major barriers to progress. CONCLUSION: Making the priority areas of information available when and where they are needed will require a coordinated approach across the health sector involving funders, providers, vendors, decision-makers and clinicians. PMID- 20581918 TI - Making 'safety' the focus of investigations into adverse events in health care. AB - This paper seeks to provide an overview for applying lessons learned in aviation safety investigation to safety investigation in the healthcare industry. There are well established regulations and procedures in aviation that make safety the end product of any accident investigation. Furthermore, standards of practice in aviation are well documented and are part of the legal code. This is currently not the case in healthcare. While healthcare has made admirable strides in improving patient safety, we maintain that concepts such as regulation, independence of investigation, standards of practice, and investigator competency to name a few, are important to move healthcare safety to the next level. PMID- 20581919 TI - The first account of a bite by the New Zealand native spider Trite planiceps (Araneae: Salticidae). AB - New Zealand has very few arthropods that pose a threat to human health. While most New Zealand spiders are considered harmless, the bite effects of most species are unknown. Here, we describe a case of a bite by a native spider, in which a young man was bitten after rolling over in his bed. The spider was collected and identified as Trite planiceps (Salticidae, black headed jumping spider), a native species commonly encountered around homes. The initial reaction was a relatively painful, sting-like, sensation, followed by the appearance of two red puncture marks and an urticarial wheal. Symptoms eventually disappeared after 72 hours, and he has had no further dermatological problems. Trite planiceps is considered to be a rather docile spider with regard to humans, but even a docile species may still bite defensively as a last resort. Notes on this species and on treatment of spider bites are provided. PMID- 20581920 TI - Myocarditis following katipo spider bite. AB - We report the case of a 22-year-old man who developed severe myocarditis following a presumed katipo spider bite. Katipo spiders are thought to be one of the most poisonous native creatures in New Zealand. No deaths from katipo spider bites have been reported since the 19th Century. A literature search reveals no previously reported cases of myocarditis following a bite from a katipo spider. The clinical presentation of latrodectism is discussed. PMID- 20581921 TI - Medical image. Angina bullosa haemorrhagica. PMID- 20581922 TI - In search of professionalism: implications for medical education. AB - This is the seventh article in an education series, discussing some of the 'hot topics' in teaching and learning in medicine. Historically, 'professionalism' was defined by the social structures of medicine, but has moved on to represent the expected behaviours and attributes of practitioners. Well publicised cases of professional misconduct, the rise of medical ethics as a discipline, and the move to a more patient-centred approach have driven the profile of professionalism into mainstream medical education. While there are many definitions of medical professionalism, there is a growing degree of consensus around what it encompasses; the way we manage tasks, our interactions with others, and looking after ourselves. The literature indicates that professionalism can be taught, learnt and applied; that attributes and behaviours can be identified; and that assessment is best approached using a range of methods over time. For learners, one of the critical factors in developing professionalism is the modelling by senior members of the profession as students move from peripheral observers to legitimate participants. Medical programmes in New Zealand are engaging with this literature in developing current curricula. PMID- 20581923 TI - Drug advertisements: what a physician should know. PMID- 20581924 TI - The future disposition of the New Zealand medical workforce. PMID- 20581925 TI - Postgraduate medical education in New Zealand: at the crossroads. PMID- 20581926 TI - Increasing medical student interest in general practice in New Zealand: where to from here? AB - INTRODUCTION: To meet increasing health demands, increasing the proportion of local graduates entering general practice is imperative. METHODS: Students entering or exiting The University of Auckland's medical programme from 2006 to 2008 were invited to complete a tracking project survey. Levels of interest in general practice were determined along with characteristics associated with a greater or lesser interest in this career. RESULTS: 712 students replied--a response rate of 80%. At entry, 40% of students had a strong interest in a career in general practice, and at exit, 29% (P =0.003). A quarter at each time point had no interest. The proportion of domestic students born outside NZ or Australia was 160/376 (42.5%). There were significantly higher levels of interest in general practice among females, students born in NZ, and those from outside Auckland--especially rural origin. Flexibility in career was more important to students with a strong interest in general practice than those with no interest. DISCUSSION: Auckland medical students have levels of interest in general practice comparable with international data. Increasing this interest further may require admission of a greater proportion of students from those groups with higher interest levels, greater emphasis on the positive aspects of general practice, and on GPs as equals to other specialists. PMID- 20581927 TI - Rural hospitals in New Zealand: results from a survey. AB - AIM: To describe the variety and range of work that New Zealand rural hospitals perform, and to examine the factors that might influence either of these, including: the characteristics of the doctors who work in rural hospitals; the facilities available; and environmental factors (such as geographical isolation and the size of the catchment population). METHOD: Structured postal questionnaire. RESULTS: There are about 44 rural hospitals in New Zealand, depending on definition. Catchment populations range from 750 to 45,000. They are staffed by either Medical Officers of Special Scale (MOSSes) or General Practitioners (GPs). They have varying levels of resources such as laboratory services and radiology services available on-site. They care for a wide range of patients and manage health conditions covering many different vocational areas of practice. CONCLUSION: Rural hospitals should be defined and recognised as a distinct entity to assist the development of appropriate vocational training pathways for their staff. They play an important and unique role in New Zealand's healthcare system which is currently unrecognised. PMID- 20581928 TI - Rural general practitioner perspectives of the needs of Maori patients requiring palliative care. AB - AIM: We aimed to identify rural general practitioners perspectives of the needs of Maori patients receiving palliative care and to discover what actions the general practitioners had undertaken to meet these needs. METHODS: This was a cross sectional postal survey of rural general practitioners. A questionnaire was developed which included a number of questions relevant to cultural needs when providing palliative care to Maori. RESULTS: 186/440 rural general practitioners responded to the survey. 52% said that they had no Maori with palliative care needs in the last 12 months, 23% had one patient and 25% had looked after 2 or more. An estimated 126/204 (62%) Maori patients had died at home. The greatest need identified by rural general practitioners when dealing with Maori patients requiring palliative care appears to be for good communication which they saw as especially important when a large family/whanau are likely to be involved. Other notable concerns were the apparent gaps in some areas for home care and the demand for more Maori nurses to be available in rural areas. CONCLUSIONS: It appeared that there was great variation in the demand for palliative care services for Maori. Some rural general practitioners rarely encounter Maori patients whilst for others caring for Maori who are in need of palliative care is an important part of their practice. There is some demand from general practice for cultural competency training and support from Maori providers and Maori services in District Health Boards. Further research in this area would be valuable. PMID- 20581929 TI - Is the prevalence of CYP2C19 genetic variants different in Pacific people than in New Zealand Europeans? AB - AIM: To undertake a preliminary assessment of the prevalence of CYP2C19 ultra rapid and poor metaboliser genetic variants in Pacific people compared with NZ Europeans. METHOD: Individuals who self-identified as either Pacific people (n=14) or NZ European (n=12) were genotyped for the *2, *3 or *17 functional variants of CYP2C19. RESULTS: There was a significantly lower frequency (P<0.01) of the CYP2C19*17 allele in Pacific people compared with NZ Europeans. No CYP2C19*17 variant alleles were detected in Pacific people in this preliminary study. CONCLUSIONS: The presence of CYP2C19*17 may be low in Pacific people and may lead to altered efficiency at metabolising some common drugs such as omeprazole. Further studies to confirm this preliminary finding are warranted. PMID- 20581930 TI - A multi-setting audit of the management of genital Chlamydia trachomatis infection. AB - AIM: To audit current management of genital chlamydia infection in the Waikato District Health Board (DHB), using 2008 Ministry of Health (MOH) management guidelines as the standard. METHODS: Any setting within Waikato DHB that diagnosed 25 or more cases of chlamydia during February-October 2008 was eligible to participate. Each site was asked to complete an audit using a proforma for 20 consecutive cases. RESULTS: Nineteen of 20 eligible sites provided data on 415 cases; 18.4% of all Waikato DHB cases during the 9 months. Treatment was documented for 380 (91.6%); of these, 369 (97.1%), or 88.9% of all 415 cases, had treatment within 28 days. Documentation of discussions with cases and outcomes was limited, restricting assessment of actual practice. Nonetheless, effective partner notification was lacking. Participants noted they had reviewed their own processes and made suggestions for improvements. CONCLUSION: The audit has identified potential gaps between recommendations within the MOH guidelines and current practice. This has helped the development of ongoing education and training resources for local providers. Further, it is hoped participation in the audit may contribute to improved case management in high-caseload settings in our district. There is commitment to re-audit to evaluate this. PMID- 20581931 TI - An audit of patients treated for syphilis at Auckland Sexual Health Service. AB - AIM: As there is no New Zealand data, an audit of patients treated for syphilis at Auckland Sexual Health Service (ASHS) was undertaken to see if management conformed to guidelines and was achieving acceptable outcomes. METHODS: Cases were initially identified from laboratory data and were categorised as being either infectious or non-infectious according to clinical and laboratory criteria. Management was compared to recommendations from ASHS treatment guidelines and treatment outcome was assessed by serological response. RESULTS: 109 cases of syphilis were identified including 9 with HIV infection (8%). Men who had sex with men were much more likely to be diagnosed with infectious syphilis than heterosexuals (p<0.0001). Fifty-one percent of infectious cases (n=35) were asymptomatic. Ninety-four percent (n=103) of cases were treated with antibiotic regimens appropriate for their clinical stage. Discrepancy in management occurred most often in the early latent and unknown duration categories. Ninety-eight cases (90%) completed the full 12 months serological follow-up period and 97% (n=92) of those had an adequate serological response to treatment. There were no treatment failures in patients with HIV infection. CONCLUSION: Current care of patients with syphilis at Auckland Sexual Health Service is achieving acceptable outcomes. Criteria for diagnosing infectious syphilis cases need to be standardised as it has implications for management and disease surveillance. MSM are a major risk group for acquisition of infectious syphilis and regular serological screening is recommended as a large proportion will be asymptomatic. PMID- 20581932 TI - The New Zealand World Health Organization Quality of Life (WHOQOL) Group. AB - With the approval of the World Health Organization (WHO), AUT University has established a new centre to develop and promote the use of the World Health Organization Quality of Life (WHOQOL) assessment instruments for health and health-related studies in New Zealand. The purpose of this paper is to introduce the NZ WHOQOL Group and to describe the structure and properties of the questionnaires in order to help the reader decide whether the instruments are suitable for their research and their use. PMID- 20581933 TI - Urban rickettsiosis in the Waikato region of New Zealand. AB - Murine typhus is the only endemic rickettsia that has been shown to cause human disease in New Zealand (NZ). We present a case report of a rickettsial infection in the Waikato region which was not typical for murine typhus. We outline the features which made this case unusual, and discuss the diagnostic uncertainty in assessing rickettsial disease. Rickettsial infection should be suspected in all patients presenting with an undifferentiated febrile illness in NZ, even if they do not fit the typical clinical and epidemiological picture of murine typhus. PMID- 20581934 TI - Anticoagulant-induced intramural haematoma of the caecum mimicking a colonic tumour. AB - Spontaneous haematoma in the intestine wall may occur. We describe a rare case. PMID- 20581935 TI - Medical image. A complication of H1N1 influenza A "swine" flu. PMID- 20581936 TI - Marketing tobacco to New Zealand women: 8 ways to reflect on "World No Tobacco Day". PMID- 20581937 TI - Australian recruitment advertising in the NZMJ. PMID- 20581939 TI - Patents. AB - 4,881,815; 4,889,412; 4,890,899; 4,890,902; 4,890,922; 4,904,066; 4,911,535; 4,913,529; 4,917,452; 4,917,476; 4,921,334; 4,936,659; 4,938,568; 4,943,709; 4,944,579. PMID- 20581938 TI - Codes, codes, and more codes. PMID- 20581940 TI - Tilted conic fitting to an off-axis conic surface. AB - A better fitting to an off-axis conic section can be obtained if a tilted conic is used. The mathematical equation for the tilting angle is obtained as well as the influence over some of the aberration coefficients. PMID- 20581941 TI - Measurement of crystal retarders. AB - We describe procedures for measuring retardation, the uniformity of retardation, and optical axis alignment of birefringent crystals. PMID- 20581942 TI - XUV optical constants of single-crystal GaAs and sputtered C, Si, Cr(3)C(2), Mo, and W. AB - The optical constants for sputtered films of C, Si, Mo, and W are presented for photon wavelengths from 13.3 to 304 A, and for single-crystal GaAs and sputtered Cr(3)C(2) from 13.3 to 1302 A. The best-fit values of the optical constants, and also the surface roughness parameter sigma, are obtained from reflectance vs incidence angle measurements using a nonlinear, least-squares curve fitting algorithm. These optical constants are significantly different from previously reported data in portions of this spectral region. The new optical data result in good agreement between theory and reflectance measurements of soft x-ray multilayer coatings made from the sputtered materials. PMID- 20581943 TI - Fluorescence response of mineral oils: spectral yield vs absorption and decay time. AB - The fluorescent emission from film samples of representative oils has been investigated by means of two independent experiments: (i) time-resolved fluorosensing at a fixed excitation frequency, by which the spectral emission yield and the associated decay times, tau(lambda), were determined, and (ii) monitoring of the integrated fluorescence in a fixed spectral band as a function of film thickness, from which extinction coefficients alpha(lambda) were derived at a number of excitation frequencies. After checking the good mutual consistency of corresponding emission data obtained in the two types of experiments, a unified analysis was elaborated in terms of a renormalized conversion efficiency, i.e., correcting the measured spectral yields for the ratio (tau/alpha). This quantity can be shown by an ppropriate model to be typical of the emitting fluorophores but independent of absorption or quenching effects due to the complex oil medium. This was indeed found to be the case for a large variety of oils, in spite of extreme variations in their absolute emission yield. PMID- 20581944 TI - Nonambiguous determination of optical constants for absorbing materials. AB - A recently proposed method for determining the optical constants of absorbing materials starting from reflectance measurements is analytically treated. The conditions for a nonambiguous determination of the optical constants are established. The values of the parameters satisfying these conditions are explicitly evaluated. PMID- 20581945 TI - Stylus profiling at high resolution and low force. AB - This paper describes experimental work to improve the lateral resolution of stylus instruments. Our efforts involve (1) use of a fine stylus, (2) low stylus load, (3) high magnification in the lateral direction, and (4) specimens with fine surface structure by which the lateral resolution of stylus instruments could be detected. By using styli with tip widths between 0.05 and 0.15-microm, a stylus load of 0.6-1.2 x 10(-6)-N (0.06-0.12-mgf), and a piezostage for lateral displacement, we detected 0.05-0.15-microm lateral resolution on the surfaces of different kinds of specimens. To get a high lateral resolution, the most important consideration is a fine stylus with small tip size. PMID- 20581946 TI - Optical multipass matrix systems. AB - Large relative aperture three- and four-objective multipass matrix systems ensuring the longest optical path length in an absorbing medium have been developed for high resolution laser spectroscopy. In these systems the images are formed on the field mirrors as compact rectangular matrices with a controlled amount of lines and columns. The number of passes may reach 500 for mirrors with high reflectivity layers. Having a simple construction, the matrix systems provide high optical and operational features. In view of their capacities the matrix systems are new generation multipass systems. PMID- 20581947 TI - Analytic solution for the three-layer multiple beam interferometer. AB - We present a simple analytic solution for the condition of constructive interference for light transmitted through an interferometer incorporating three ideally transparent layers of arbitrary thickness and refractive index. We also consider the effect of adding two metallic coatings to the outer surfaces of the interferometer and give empirical expressions for the associated phase changes for silver coatings on silica, sapphire, and mica substrates. A particular application to fringes of equal chromatic order can be utilized to obtain precise measurements of the thickness of extremely thin films sandwiched between two substrates. PMID- 20581948 TI - Quasimonochromatic white light fringe interferometer. AB - Quasimonochromatic light sources, such as laser diodes and high power LEDs, are investigated to determine their suitability for zero path difference determination using white light fringes in a Michelson interferometer. Fringe visibility curves are theoretically determined for various combinations of light sources and compared with experimental results when used in a Michelson interferometer with a 25-m path length. A resolution of 2-3 microm was obtained for a pair of multimode laser diodes and also for a single multimode laser diode operated as an LED. This is more than adequate for the calibration of survey baselines. PMID- 20581949 TI - Photothermoelastic evaluation for small mechanical structures. AB - We describe a photothermal technique for testing the mechanical properties of small mechanical structures. Irradiation with chopped laser light on platelike or beamlike structures produces flexural vibration caused by thermoelastic bending. By monitoring the vibration, we can develop useful techniques for evaluating thickness, size attachment, tension, and adhesion of small mechanical structures. The technique will be useful for inspecting small mechanical structures that are fabricated with lithographic processes for various high technology applications. PMID- 20581950 TI - Moire null topography with uniform accuracy by double computer-generated gratings. AB - A method of moire null testing with two computer-generated gratings is proposed. Based on our theoretical analysis, it is concluded that uniform accuracy is possible only when the lateral derivative of the moire kernel of the project grating is a constant. Moreover, the design of the kernels of the two gratings is believed to give an equidistant straight fringe background. Therefore, the defect of the tested object from the standard shape can be easily found directly from the fringe shift, with uniform accuracy. Computer simulations as well as experimental results of the test of a toroid surface are presented. PMID- 20581951 TI - Holographic investigation of residual deformations induced by a pulsed ion implanter. AB - A new use of holographic interferometry to investigate the residual deformations induced in nitrogen implanted specimens by a plasma focus device is reported. The method is simple and nondestructive. Experimental results obtained for AISI 304 stainless steel specimens are presented. PMID- 20581952 TI - Local OH concentration measurement in atmospheric pressure flames by a laser saturated fluorescence method: two-optical path laser-induced fluorescence. AB - The first (to our knowledge) measurements of number density of OH in flames at atmospheric pressure by TOPLIF are reported. TOPLIF (acronym for two optical paths laser-induced fluorescence) improves the accuracy of LIF measurements by taking into account both the spatial profile of the exciting laser intensity and the collisional transfer rate. The method is based on simultaneously recording the LIF signals from focal volumes of two different shapes. The ratio of the signals is a measure of the saturation parameter (which depends on the laser intensity and the quenching) using which accurate determination of the species number density can be deduced from the fluorescence signals. The method is valid as far as at least partial saturation is reached. First, experimental verification of the theoretical basis of the method is reported. The population of a single rovibronic level is measured as it is in most of the spectroscopic methods. TOPLIF measures this population relative to this level's population in a chosen reference flame. Absolute value can therefore be obtained if the value in the reference flame is known or measured. Absolute [OH] profiles obtained in flat flames burning at 60 and 1000 mb are presented and compared to laser absorption measurements. PMID- 20581953 TI - Fiber optic reflectance spectrophotometry system for in vivo tissue diagnosis. AB - Fiber optic probes for a small portable reflectance spectrophotometry system for noninvasive clinical diagnosis have been developed. A slender fiber optic probe, 3 m long, 2.4-mm diameter, which goes into the channel of a fiber optic endoscope, has been developed as the standard probe. To expand the availability and capability of this reflectance spectrophotometry system, some variations of the fiber optic probes were developed: contact sensor, pressure sensor, attachments for dental use, and a modified-shape probe head for continuous monitoring. The feasibility of these fiber optic probes was examined experimentally. PMID- 20581954 TI - Rainbows: Mie computations and the Airy approximation. AB - Efficient and accurate computation of the scattered intensity pattern by the Mie formulas is now feasible for size parameters up to x = 50,000 at least, which in visual light means spherical drops with diameters up to 6 mm. We present a method for evaluating the Mie coefficients from the ratios between Riccati-Bessel and Neumann functions of successive order. We probe the applicability of the Airy approximation, which we generalize to rainbows of arbitrary p (number of internal reflections = p - 1), by comparing the Mie and Airy intensity patterns. Millimeter size water drops show a match in all details, including the position and intensity of the supernumerary maxima and the polarization. A fairly good match is still seen for drops of 0.1 mm. A small spread in sizes helps to smooth out irrelevant detail. The dark band between the rainbows is used to test more subtle features. We conclude that this band contains not only externally reflected light (p = 0) but also a sizable contribution f rom the p = 6 and p = 7 rainbows, which shift rapidly with wavelength. The higher the refractive index, the closer both theories agree on the first primary rainbow (p = 2) peak for drop diameters as small as 0.02 mm. This may be useful in supporting experimental work. PMID- 20581955 TI - Significance of anisotropy and the outer scale of turbulence for optical and radio seeing. AB - The small value found for the outer scale of turbulence (namely, 20 dB), and moderate drive voltages for frequencies up to several megahertz at 633-nm wavelength. PMID- 20581987 TI - Measurement of distributed strain due to laying and recovery of submarine optical fiber cable. AB - Strain distribution due to cable laying and recovery is measured, using Brillouin optical fiber time domain analysis in a 3.7-km long submarine optical fiber cable. We believe this is the first time that the residual strain distribution in the recovered submarine cable has been measured. The residual strains measured in some cable sections due to the cable laying and recovery are found to be as small as 0.02 and 0.04%, respectively. PMID- 20581988 TI - Examination of two-step fabrication methods for single-mode fiber compatible ion exchanged glass waveguides. AB - A computer model was used to study important two-step ion-exchange processes for fabrication of singlemode optical waveguides with fiberlike mode field distributions. As a first process step, a field-assisted method was calculated to have a better controllability than a diffusion method. As a second process step, field-assisted burial was found to optimize the coupling loss to fiber to 0.05 dB, but losses lower than 0.2 dB were calculated also for less complex diffusion process steps. On the basis of modeling, a solid state fabrication process was proposed, and the near field distributions of fabricated waveguides were measured to confirm the model. PMID- 20581990 TI - Patents. AB - 4,896,326; 4,907,887; 4,938,205; 4,940,304; 4,940,316; 4,941,093; 4,946,245; 4,948,225; 4,953,923; 4,955,693; 4,957,366; 4,955,701; 4,957,335; 4,960,312. PMID- 20581989 TI - Fabry-Perot effects in the exponential decay and phase shift reflectivity measurement methods. AB - The exponential decay and phase shift reflectivity measurement methods are examined for a real optical cavity, i.e., one that includes mechanical vibrations and light source fluctuations in wavelength and amplitude. We compare the two methods and examine the problems inherent in each and present methods for overcoming these. Both methods are shown to be excellent for measuring high reflectivity cavity losses (particularly for the free electron laser case) although suitable precautions should be taken. PMID- 20581991 TI - Temporal response of atmospheric turbulence compensation. AB - The temporal kernel for the phase error variance due to atmospheric turbulence is calculated. This kernel, convolved with the servo transfer function, determines the temporal error of any turbulence compensation scheme. PMID- 20581992 TI - Video camera measurements of atmospheric turbulence using the telescope image of a distant light source. AB - We report on a simple technique to measure experimentally the refractive index structure parameter C(2)(n) of the atmosphere along a horizontal path. PMID- 20581993 TI - Measurement of the photoemission of two electrons from a multialkali photocathode. AB - Two-electron emission per incident photon, measured for a multialkali photocathode, shows a steep onset at 2700 A and increases to 14% of the total quantum efficiency at 2000 A. PMID- 20581994 TI - Refractive index modulation mechanism in bleached silver halide holograms. AB - We present a simple technique for observing and studying the onset of microstructure in silver halide gratings, which can also be used to improve processing chemistry. PMID- 20581995 TI - Residual aberration corrections in far field in-line holography using an auxiliary off-axis hologram. AB - To obtain a diffraction-limited resolution with a lens assisted Fraunhofer hologram reconstructed by a reverse reference beam, residual aberrations have been corrected by using an auxiliary off-axis hologram. PMID- 20581996 TI - Instrumental broadening caused by the misalignment function in a Fabry-Perot etalon assembly. AB - This Technical Note discusses the contribution to broadening from lack of parallelism of the etalon plates. PMID- 20581997 TI - Revised Dove prism formulas. AB - Examination of the known formulas of the Dove prism led to their revision. The variation of the revised length and weight of the Dove prism as a function of prism base angle is depicted for BK7 and SF6 glasses and interpreted. PMID- 20581998 TI - A method to resolve the 180 degrees ambiguity in speckle photography. AB - A new way of resolving the 180 degrees ambiguity in speckle photography is presented. Results from a study of the deformation of a wooden block caused by drying illustrates the method. PMID- 20581999 TI - Approximation to true peak absorbance from observed peak absorbance for gas phase Fourier transform spectroscopy. AB - We have developed an approximation that provides a fast reasonably accurate estimate of the halfwidth at half-height of a single pressure-broadened line. PMID- 20582000 TI - Collimating a coherent processor or diffractometer: a rapid method. AB - Correct setting of the collimating lens is identified when diffraction spot separation on a video display is invariant to gross axial displacement of a grating. PMID- 20582001 TI - High temperature 180 degrees laser-induced fluorescence probe for remote trace radical concentration measurements. AB - The design and validation are described of an optical probe for measurements of parts per million OH concentrations in actual combustion environments (1100 K, 1 atm). PMID- 20582002 TI - Light scattering by inclusions in crystals. AB - Optical transmission data can aid in the analysis of nonabsorbing inclusions in crystals. For illustration, the inclusions in a AgGaSe(2) sample are analyzed. PMID- 20582003 TI - Extreme ultraviolet transmission of a synthetic diamond thin film. AB - The transmission of a thin film of synthetic diamond was measured at various wavelengths in the extreme ultraviolet. The measurements agree with a prediction based on published carbon attenuation coefficients assuming the density of natural diamond. A betterfit to the data results when an additional approximately 200-A layer of silicon is included in the model. It is believed that this silicon layer exists as silicon carbide. PMID- 20582004 TI - ATMOS data processing and science analysis methods. AB - The ATMOS (atmospheric trace molecule spectroscopy) instrument, a high speed Fourier transform spectrometer operating in the middle IR (2.2-16 microm), recorded more than 1500 solar spectra at approximately 0.0105-cm(-1) resolution during its first mission onboard the shuttle Challenger in the spring of 1985. These spectra were acquired during high sun conditions for studies of the solar atmosphere and during low sun conditions for studies of the earth's upper atmosphere. This paper describes the steps by which the telemetry data were converted into spectra suitable for analysis, the analysis software and methods developed for the atmospheric and solar studies, and the ATMOS data analysis facility. PMID- 20582005 TI - Laser beam propagation in turbulent conditions. AB - Diffraction-limited low power laser beams at 1.06 and 3.8 microm were focused by a 91-cm diam aperture onto a receiver located 10.5 km away on a low slant angle path over a desert basin. The analysis of beam areas and turbulence levels was used to determine a new scaling law for tilt-corrected turbulence-induced beam spread. PMID- 20582006 TI - Frequency modulation spectroscopy at 1.3microm using InGaAsP lasers: a prototype field instrument for atmospheric chemistry research. AB - Two-tone frequency modulation spectroscopy has been used in conjunction with InGaAsP lasers in the 1.3-microm region to monitor weak water vapor absorptions in a long path White cell. Detection electronics that reduce the effect of Johnson noise are described. The system was capable of detecting optical densities corresponding to <1.7 x 10(-6) in a 1-Hz bandwidth. Factors limiting the difference between observed and shot noise limited performance for these types of laser and condition are discussed. PMID- 20582007 TI - Estimation of visibility from satellite imagery. AB - This work examines methods for estimating visibility from satellite imagery, which employ information from the spatial and frequency domains. Properties of luminance and contrast images are derived and compared in both domains. In the past, contrast has traditionally been employed to measure the effects of atmospheric attenuation on visibility. However, the derived results show that the luminance image in either domain contains all the necessary information to calculate standard visibility parameters. Two methods are presented which estimate representative parameters. PMID- 20582008 TI - TV holography: spatial resolution and signal resolution in deformation analysis. AB - We discuss the resolution limits of digital TV holography used for nondestructive testing. A phase shifting technique converts the interferometric information into a phase distribution image. Spatial low pass filtering improves the phase accuracy at the expense of spatial resolution. Experiments show that spatial details down to 2.5 x 2.5 pixels and displacement below lambda/100 may be resolved. PMID- 20582009 TI - Achromatic prism retarder for use in polarimetric sensors. AB - The optical resting point of a polarimetric sensor is normally reached by using a fixed retarder plate. It is shown that this retarder plate can be omitted by using 90 degrees prisms of selected glass materials. The sensitivity of the prism retarder toward changes in wavelength and temperature is mathematically analyzed, and it is shown how the stability of the retarder system is influenced by the selection of materials and production tolerances on prism angles. A practical example is given. PMID- 20582010 TI - Signal-to-noise ratio analysis in laser absorption spectrometers using optical multipass cells. AB - In high resolution absorption spectrometers with conventional light sources, the signal-to-noise ratio (SNR) is usually limited by the thermal noise level of the detector-preamplifier combination, which is independent of the light source power. However, the noise in many laser absorption spectrometers is dominated by the excess or shot noise which is dependent on the transmitted laser power, and which in turn is dependent on the number of reflections in a multipass cell. The optimum absorption path length for a high frequency modulated (FM) and a conventional wavelength modulated (WM) diode laser absorption spectrometer is investigated in this paper. The major result is that, due to the power attenuation by the multipass cell, the best SNR of a shot noise limited FM spectrometer is achieved at substantially shorter absorption paths, when compared with the excess noise limited WM spectrometer. This finding implies that the implementation of the FM technique in absorption spectrometers with multipasscells can improve the SNR only by 1 order of magnitude. Although desirable, this is substantially less than the improvement of 2 orders of magnitude expected in quantum limited conditions with a single pass cell. PMID- 20582011 TI - Terrestrial polarization imagery obtained from the Space Shuttle: characterization and interpretation. AB - An experiment to measure the polarization of land, sea, haze, and cloud areas from space was carried aboard the Space Shuttle in Sept. 1985. Digitized polarimetric and photometric imagery in mutually perpendicular planes was derived in the red, green, and blue spectral regions from photographs taken with two synchronized Hasselblad cameras using type 5036 Ektachrome film. Digitization at the NASA Houston Video Digital Analysis Systems Laboratory permitted reduction of the imagery into equipolarimetric contours with a relative accuracy of +/-20% for comparison to ground truth. The Island of Hawaii and adjacent sea and cloud areas were the objects of the specific imagery analyzed. Results show that cloud development is uniquely characterized using percent polarization without requiring precision photometric calibration. Furthermore, sea state and wind direction over the sea could be inferred as well as terrestrial soil texture. PMID- 20582012 TI - Laser remote sensing of aquatic environment: first- and second-order scattering model. AB - Transport of a small divergent (of several millirads) laser beam in shallow waters has been investigated. A simple model was developed to describe and calculate the first- and second-order power and energy flux. From evaluation of the truncation error the applicability of the second-order approach for clear waters is concluded. On the other hand, turbid waters can be treated by introducing an effective beam attenuation coefficient. The computations were performed for different geometrical configurations of a lidar system and for diverse aquatic conditions. Finally, an alternative method for remote sensing of the concentration of particulate material by an airborne lidar instrument is proposed by using off-axis detection. PMID- 20582013 TI - Total luminescent spectroscopy for remote laser diagnostics of natural water conditions. AB - In undertaking the rapid diagnostics of water conditions (for organic impurities, eutrophication etc.), it is expedient to confine the effort to establishing the statistically normal state and departures from it rather than to seek the full chemical composition of the medium. What others have termed spectral signatures obtained by such methods as total luminescent spectroscopy can serve as representative indicators of both background conditions and those deviating from the normal. In this paper we show how, with the aid of laboratory catalogs of spectral signatures, it is possible to detect oil pollution at levels substantially below those of slicks (of a few microliters per liter) and to identify groups of pollutants (by remote sensing). And we describe a spectroscopic lidar we developed for marine studies. PMID- 20582014 TI - Resonance structures in elastic and Raman scattering from microspheres. AB - To study the interactions between Mie scattering and Raman emissions of spherical particles, we measured the Raman spectra together with the elastically scattered light of the excitation source of an evaporating aqueous sodium nitrate droplet. Resonance structures were observed in the temporal profiles of the elastically scattered light and Raman nitrate and water emissions. The resonance structures in these three profiles occurred in a concerted mode but sometimes occurred independently of each other. A model of inelastic scattering by microspheres by Kerker et al. ["Raman and Fluorescent Scattering by Molecules Embedded in Spheres with Radii up to Several Multiples of the Wavelength," Appl. Opt. 18, 1172-1179 (1979); "Lorenz-Mie Scattering by Spheres: Some Newly Recognized Phenomena," Aerosol Sci. Technol. 1, 275-291 (1982); "Inelastic Light Scattering," in Aerosol Microphysics I: Particle Interaction, W. H. Marlow, Ed. (Springer-Verlag, New York, 1980); "Model for Raman and Fluorescent Scattering by Molecules Embedded in Small Particles," Phys. Rev. A 13, 396-404 (1976)] and the behavior of low order Mie resonances were used to explain the data. This type of data can be used for the determination of chemical compositions of spherical particles. PMID- 20582015 TI - Interpretation of integrating sphere signal output for nonideal transmitting samples. AB - A simple model for transmittance measurements with an integrating sphere is presented. The scattered light is divided into three components, each resulting in its own separate contribution to the detector signal. These contributions depend on the scattering angle and mode of operation. The true specular, diffuse, and total transmittance values are obtained as functions of the signal outputs from a reference reading, a total transmittance reading, and a diffuse transmittance reading. Two different modes of operation are distinguished involving a BaSO(4) plate and an Al mirror. Experimental results are presented illustrating the model for two samples with different scattering characteristics. PMID- 20582016 TI - Extinction and scattering by soft spheres. AB - On the basis of an approximate relation, the Mie series are replaced by new ones, which can be summed exactly with the aid of various modified and generalized forms of the addition theorem for cylindrical functions. The sums obtained simultaneously simplify the initial expressions for the scattering characteristics and preserve their analytical nature. The conventional approximations for the amplitude functions and the efficiency factors rigorously follow from the new approaches if the optical parameters are properly restricted. The acceptable domains of these approaches contain the long wavelength region and are extensive enough to study the various (including inverse) scattering problems for the real disperse systems, in which the particles are suspended in a medium with similar optical properties. PMID- 20582017 TI - Voltage-current relationship for flashlamps: an empirical approach. AB - This paper presents the results of an empirical study of the voltage-current relationship of flashlamps. It is shown that the Goncz and Marotta relationships are limited in that they can only be used in certain current density regimes. Based on empirical data, a generalized empirical voltage-current relationship is proposed. In particular, the generalized form is found to be a voltage-current relationship with a power factor. This power factor is found to be a function of the current density of the flashlamp. The relationships used in the past are found to fit this generalized form according to their respective current density regimes. PMID- 20582018 TI - Effective media equivalent to an asymmetric multilayer and to a rough interface. AB - A computer fitting program is used to show that not only a symmetric but also an asymmetric multilayer, composed of a periodic structure with small thickness irregularity or with slightly rough interfaces, can be equivalent to an anisotropic single layer within a good approximation. It is also shown that an interface layer equivalent to a rough interface does not exist, in spite of the fact that such an assumption has widely been used. PMID- 20582019 TI - Stress, scatter, and structure dependence on composition of thin films of Si YF(3) and ZnSe-SrF(2). AB - Composition dependent structural, optical, and mechanical properties of codeposited thin films were studied in the Si-YF(3) and ZnSe-SrF(2) systems. Intrinsic stress varies nonlinearly in both systems. In the Si-YF(3) system, the stress becomes slightly compressive for intermediate compositions, even though it is highly tensile in the pure constituent thin films. In the ZnSe-SrF(2) system, optical scatter and intrinsic stress exhibit abrupt changes at approximately 60 vol % SrF(2), accompanied by a change in the dominant crystalline orientation. Possible structure-property relationships and composition ranges for practical applications of thick films are also discussed. PMID- 20582020 TI - Implementing receptive fields with excitatory and inhibitory optoelectrical responses of bacteriorhodopsin films. AB - The sign of the optoelectrical response of bacteriorhodopsin is highlighted as a means to emulate excitation and inhibition in neural computation. A classic example of a neural computation that is based on such excitation and inhibition is chosen to highlight the unique applicability of bacteriorhodopsin in highly parallel computational schemes. The classic example chosen is that of the ganglion receptive field, which is a fundamental element in retinal edge detection. Dried bacteriorhodopsin films are constructed that effectively act as receptive fields because of the sign of their photoresponse. The results on these simple bacteriorhodopsin receptive fields are extended to schemes that incorporate with greater elegance this unique ability of bacteriorhodopsin to exhibit excitation and inhibition. Experiments are presented that test some of these advanced ideas in bacteriorhodopsin parallel computation. PMID- 20582021 TI - Optimal real correlation filters. AB - Expressions are derived for real filters that have a maximum correlation signal to noise ratio. Both continuous and discrete cases are treated and shown to have similar forms. The signal can be complex, and the case of a real signal is considered and related to previous results. PMID- 20582022 TI - Integrated optic matrix-vector multiplier using multifrequency acoustooptic Bragg diffraction. AB - An integrated optic numerical processor performing matrix-vector multiplication in an analog representation is proposed. Parallel processing of a number of numerical products is made in the same area of a substrate by means of multiple Bragg diffraction of multiwavelength optical signals due to multifrequency surface acoustic waves. The wavelength interval of multiplexed optical signals can be 0.77 nm for the optical beamwidth of 3 mm and the acoustic frequency of 1 GHz. Preliminary demonstrations of matrix-vector multiplication are presented with a waveguide type Ti:LiNbO(3) acoustooptic deflector. An alternative processor using one optical wavelength is also described. PMID- 20582023 TI - Fast digital optical multiplication using an array of binary symmetric logic counters. AB - Because of the lack of fast, accurate, and large dynamic range analog-to-digital converters (ADCs), optical implementation of the digital multiplication through analog convolution (DMAC) algorithm yields a slow digital multiplier. By replacing both the optical adder and ADC arrays by an optical combinatorial logic counter array, a new optical fast digital multiplication method is proposed. Compared to the existing optical DMAC scheme, the new method promises both higher processing speed and accuracy. A comparison of this and some of the other optical and electronic fast digital multiplication schemes is also presented. PMID- 20582024 TI - Parallel implementation of optical symbolic substitution logic using shadow casting and polarization. AB - We propose a parallel implementation method for optical symbolic substitution logic. The method uses shadow-casting principles for the efficient implementation of fundamental operations required in symbolic substitution logic; namely, image replication, spatial shifting, and combination. The use of light polarization allows for the implementation in parallel of several substitution rules without replicating the input image. The distinctive features of the method include light efficiency, flexibility, cascadability, and programmability. PMID- 20582025 TI - Gamma ray imaging using coded aperture masks: a computer simulation approach. AB - The gamma-ray imaging using coded aperture masks as focusing elements is an extended technique for static position sensitive detectors. Several transfer functions have been proposed to implement mathematically the set of holes in the mask, the uniformly redundant array collimator being the most popular design. A considerable amount of work has been done to improve the digital methods to deconvolve the gamma-ray image, formed at the detector plane, with this transfer function. Here we present a study of the behavior of these techniques when applied to the geometric shadows produced by a set of point emitters. Comparison of the shape of the object reconstructed from these shadows with that resulting from the analytical reconstruction is performed, defining the validity ranges of the usual algorithmic approximations reported in the literature. Finally, several improvements are discussed. PMID- 20582026 TI - Performance evaluation of minimum average correlation energy filters. AB - A new SDF type correlation filter referred to as the minimum average correlation energy (MACE) filter has been recently described in the literature. In this paper, we experimentally address the distortion tolerance and noise properties of this filter. The MACE filter has attractive properties that include: easily detectable peaks, distortion invariance, simplified training set selection, solutions to input bias effects, performance in noise and real background clutter, and less clutter with its reduced number of training set images. Each of these properties is investigated in detail in this paper. PMID- 20582027 TI - Reconstruction of tomographic images from sparse data sets by a new finite element maximum entropy approach. AB - A new algorithm for the reconstruction of tomographic images from sparse data sets is presented. A finite element technique was devised to solve the constrained optimization problem which resulted from the analysis using the maximum entropy formalism. The improvement in reconstruction image quality over conventional techniques is illustrated by several examples. PMID- 20582028 TI - Acousto-electro-optic phase gratings for optical signal processing applications. AB - Electrooptic and acoustooptic phase gratings perform many useful operations and often compete with each other for similar applications. Using piezoelectric crystals, it is possible to generate a simultaneous acoustoelectro- optic (AEO) grating, which has advantages over applying either effect separately. The AEO effect using surface acoustic waves and electrooptic interdigital transducers is discussed. Coupled mode theory has been used to analyze the resulting diffraction effects, and experimental results in both the Bragg and Raman-Nath regimes are reported. The device can perform fundamental operations such as convolution, correlation, and optical matrix processing. We propose AEO components for use in spread spectrum systems, hybrid optical bistability, and adaptive phased array antenna control. PMID- 20582030 TI - Applied optics. PMID- 20582029 TI - Elements of a unique bacteriorhodopsin neural network architecture. AB - A rapidly reprogrammable neural network architecture with the possibility for a large synapse matrix is presented. The concept is based on the use of bacteriorhodopsin as a molecular computational element with electrooptical characteristics that are associated with a series of intermediates that are photochemically initiated. One of these states has been stabilized by several orders of magnitude with specific environmental conditions, and this allows the concentration of intermediates to be readily affected without the need for continuous holding illuminations. Thus, the photoelectrical characteristics at each synapse can readily be modulated, and a scheme has been devised to read the synaptic matrix without erasing the impressed synaptic strengths. Electrical measurements are presented to test specific aspects of the overall neural network implementation, and the results of these measurements are encouraging for the development of such a distinctive neural network device. PMID- 20582031 TI - Lasers and photonics. PMID- 20582032 TI - Nasa patter. PMID- 20582033 TI - Applied optics of optics and opticists. PMID- 20582034 TI - Stokes shifted laser lines in KrF-pumped hydrogen: reduction of beam divergence by addition of helium. AB - The beam divergences of the recollimated Stokes shifted lines of H(2) excited by a focused KrF laser are reduced by addition of helium. PMID- 20582036 TI - Efficient coupling of multiple diode laser arrays to an optical fiber by geometric multiplexing. AB - Efficient coupling of three diode arrays to a multimode fiber has been demonstrated. Coupling of over 100 of these sourcesshould be possible. PMID- 20582035 TI - Efficient, spectrally narrow pulsed dye laser using a volume holographic transmission grating. AB - A pulsed dye laser is described in which a frequency is selected using a volume holographic transmission grating and a tuning mirror. We obtained a 20% energy conversion efficiency and a linewidth of 3 GHz at 560 nm. PMID- 20582037 TI - Twin-core optical fiber with large core ellipticity. AB - The first (we believe) twin-core optical fiber with large core ellipticity has been fabricated, and its significant polarization dependent coupling properties have been demonstrated. PMID- 20582038 TI - Optical cavity design for long pulse excimer lasers. AB - The design and performance of various optical resonator cavities are described for a 1-J XeCl discharge laser with a 200-ns FWHM optical pulse. Advantages inherent in many cavity round trips for efficiently controlling linewidth, spatial coherence, and polarization are indicated. PMID- 20582039 TI - Variable-ratio tap for plastic optical fiber. AB - A variable-ratio tap is developed by changing the bending radius of a plastic optical fiber. When a plastic fiber is bent over a small radius, the core modes of the fiber are converted into the cladding modes, which can be extracted through material having a suitable refractive index. The transmission characteristics of the variable-ratio tap are investigated using the ray tracing technique governing the quasiskew rays propagating through a multimode fiber. PMID- 20582040 TI - Monolithic wavelength-flattened 1 x 7 single-mode fused fiber couplers: theory, fabrication, and analysis. AB - The basic theory of monolithic 1 x 7 couplers is presented. The results of fabricating eighty-two devices are described, and the steady improvement in achieved device performance is shown leading to the fabrication of a controlled batch of eleven devices. These devices have excess losses of <0.1 dB together with good coupling uniformity to the seven output fibers. Maximum insertion losses are all around 10 dB or less, which is seen to compare favorably with devices obtained by concatenating 2 x 2 couplers. It is shown that to obtain an equal power split between the center and outer fibers it is necessary to control carefully the degree of fusion of the structure. An analysis of this coupling behavior is presented. PMID- 20582041 TI - Theory of fiber optic radiometry, emissivity of fibers, and distributed thermal sensors. AB - This paper formulates a general radiometric theory of multimode step index fibers, covering in particular the region of mid- and far IR fibers. The optical fiber is treated both as a passive waveguide, guiding the external radiation injected into it, as well as an active waveguide, generating internal thermal radiation which is guided to both fiber endfaces. Several fiber absorption profiles are considered. In other words, the thermal radiation sources coupling radiation into the guided modes of the fiber are in one case considered to be distributed in the core, and in another, to be distributed in the cladding. The model is based on 3-D optical geometry of bounded and tunneling skew rays and yields an analytical expression for the angular power distribution along the length of the fiber. The radiation emissivity of multimode fibers is formulated. Based on the model, the theory of a new fiber optic distributed thermal sensor is presented. This sensor needs no external source of radiation for its operation and is based on the self-generation of thermal radiation in a modified IR fiber. Such a sensor can be produced by deliberately inducing surface or bulk absorption in the fiber core or coating (cladding) a bare fiber core with an IR absorbing material. PMID- 20582042 TI - Modeling of the index change in K(+)-Na(+) ion-exchanged glass. AB - We have measured the surface index change and birefringence in K(+)-Na(+) ion exchanged waveguides and compared the results with theory. The contribution to the index change caused by the polarizability/volume changes (Deltan(p)) is calculated using two theoretical models which use empirical relations based on the glass composition. In both cases, we encounter large discrepancies between the predicted and measured values which are attributed to the inherent deficiency in the models, which assume free expansion of the glass in calculating the volume changes. Recognizing that the net volume change is much smaller, we accurately measure its value and show that both models can be used to predict Deltan(p) with the same accuracy, provided that the correct volume change is used. We show that the limitation in accuracy is dictated by measurement errors and uncertainties in the values of the ionic radii and polarizabilities. We also present a unique and systematic method for determining the compressive stress generated in the glass resulting from ion exchange. PMID- 20582043 TI - Evaluation of antireflection coatings for optical waveguides. AB - A simple new technique is presented for evaluating the structural parameters of antireflection coating films formed on optical waveguide facets. SiO(x)/MgF(2) double layer AR coatings are fabricated on silica based optical waveguide facets by the thermal evaporation method. The transmission properties of the waveguides are measured in the 0.5-1.7-microm wavelength region. The structural parameters (refractive index and thickness) of the SiO(x) and MgF(2) films are determined by fitting the theoretical transmission properties to the experimental results by iteratively changing the parameters for calculation. The calculated reflectivity is in good agreement with the value measured with an optical time domain reflectometer. A graphic method for the simple determination of the parameters is also discussed. PMID- 20582045 TI - Determining hazard distances from non-Gaussian lasers. AB - A simple method is presented for determining the nominal ocular hazard distance from non-Gaussian laser beams. The simplified method currently used for laser safety calculations when determining the laser beam diameter as a function of distance produces errors in the near field. The irradiance or radiant exposure of multimode and non-Gaussian laser beams in the near field may be calculated more precisely by the use of a simple proposed relationship with easily determined parameters. PMID- 20582044 TI - Measurement of distributed losses in optical waveguides: a new technique. AB - An accurate measurement method for waveguide loss measurement is reported which is suitable for the determination of low values of distributed loss in integrated optical waveguides. The technique is insensitive to the values of other circuit characteristics such as splitter loss and splitting ratio; indeed it provides a means of evaluating most relevant circuit parameters. The concept is demonstrated through the use of discrete single-mode fiber optical components, and it is shown that the method is capable of generating repeatable measurements of waveguide loss with good accuracy. PMID- 20582047 TI - Patents. AB - 4,958,896; 4,958,919; 4,958,898; 4,958,931; 4,960,323; 4,960,324; 4,961,622; 4,961,625; 4,961,634; 4,962,492; 4,964,722. PMID- 20582046 TI - Laser scanning system using a rotationally asymmetric aspheric surface. AB - In recent laser beam printers, higher resolution and a more compact system design are always desired. In this study, a rotationally asymmetric aspheric surface is introduced to achieve these purposes. This surface can completely eliminate field curvature aberration caused by the oblique incidence of the laser beam to the scanning optics, achieving high resolution over a wide scanning range. PMID- 20582049 TI - Applied optics of optics and opticists. PMID- 20582050 TI - Whole field in-plane vibration analysis using pulsed phase-stepped ESPI. AB - Electronic speckle pattern interferometry has been used to study resonant in plane vibrations of a thin square metal plate. An in-plane sensitive arrangement is used with dual-beam illumination from a pulsed laser. Fringe patterns are formed which show a cosinusoidal intensity profile. These fringe patterns inherently carry phase information, which is extracted using the single phase step technique and analyzed to determine the amplitude and phase for the horizontal and vertical components of in-plane vibration. These are automatically combined to yield the total in-plane vibration mode. The final result is displayed as vectors drawn over an image of the object. PMID- 20582051 TI - Comparative phase shifting holographic interferometry. AB - This paper reports on the application of phase shifting interferometry to comparative holography. The method here enables the measurement of phase distributions corresponding to the difference in displacements of two nominally identical specimens subjected to similar loading steps. Different aspects of the method are discussed, and experimental results are presented to demonstrate the feasibility and versatility of the technique in flaw detection. PMID- 20582052 TI - Fiber optic phase stepping system for interferometry. AB - A closed loop phase control system using an all-fiber optical configuration has been developed for use in phase stepping interferometry. This system drives the relative phase of two interfering beams through a sequence of pi/2 rad increments so that the initial relative phase of these beams can be determined. This phase stepping system uses optical fibers to provide spatially uniform phase steps from a flexible, easily aligned optical configuration. In addition, this system uses phase feed back to eliminate phase modulator errors and to compensate for phase drifts caused by environmental disturbances. PMID- 20582053 TI - Interferometric measurement of group and phase refractive index. AB - An experimental apparatus has been designed to measure group refractive index (n(g)) by observing the shift of the fringe visibility envelope upon insertion of a sample into one arm of a Twyman-Green interferometer. A criterion is developed for the limiting bandwidth and thickness for which good visibility may be expected and for predicting the bandwidth for the narrowest visibility curve. It is demonstrated that the measured group index data can be converted to phase index data with a previously described technique [J. R. Rogers and M. D. Hopler, J. Opt. Soc. Am. A 5, 1595-1600 (1988)] to an accuracy of approximately 0.0006 across the visible spectrum. PMID- 20582054 TI - Grating interferometer with extremely high stability, suitable for measuring small refractive index changes. AB - We describe here a grating interferometer with extremely high stability and which can be used as a differential refractometer. The instrument uses heterodyne techniques to achieve high sensitivity. We present an analysis of the operation of the system and results which show that it has a long term stability of the order of 1/1500 wavelength over 2 h. PMID- 20582055 TI - Homogeneity testing of optical glass by holographic interferometry. AB - A holographic interferometry technique for the measurement of optical glass homogeneity of plate samples is presented. It is shown that this immersion technique is more accurate than methods used for this purpose based on classical interferometry without the need of quality optics. PMID- 20582056 TI - Trace detection of hydrazines by optical homodyne interferometry. AB - A photothermal laser interferometric system is described that has sufficient sensitivity to allow the detection of the hydrazines: hydrazine, monomethylhydrazine, and unsymmetrical dimethyihydrazine at part per billion concentrations. A line tunable CO(2) laser excites the trace hydrazine molecules in one arm of a modified Jamin interferometer illuminated with a single frequency He-Ne laser. The CO(2) laser beam intersects one of the He-Ne beams in the interferometer at a small angle, so there is no interaction of the IR and visible laser beams at any optical components in the system. The system operates with computer control of interferometer alignment, CO(2) excitation laser tuning, and data acquisition. PMID- 20582057 TI - Higher-order analysis of four-beam cross grating interferometers. AB - Both on- and off-axis four-beam interference patterns are analyzed using ray tracing. The cross gratinglike interference pattern is accompanied by an extra term which consists of two orthogonal two-beam interference patterns. When partially coherent light is used, the extra term generally degrades the contrast of the cross gratinglike pattern unless some special kinds of source are utilized. With gratings of high spatial frequencies, the amplitude of the extra term can become large compared with the desired term. Consequently, the localized cross gratinglike pattern is changed to be periodic in different directions. PMID- 20582058 TI - New method of asymmetric flow field measurement in hypersonic shock tunnel. AB - In this paper a method of large aperture (?500 mm) high sensitivity moire deflectometry is used to obtain multidirectional deflectograms of the asymmetric flow field in hypersonic (M = 10.29) shock tunnel. At the same time, a 3-D reconstructive method of the asymmetric flow field is presented which is based on the integration of the moire deflective angle and the double-cubic many-knot interpolating splines; it is used to calculate the 3-D density distribution of the asymmetric flow field. PMID- 20582059 TI - Double exposure planar transmission holograms recorded in nonlinear dichromated gelatin. AB - A coupled wave model is used to describe the replay of two transmission gratings (G(1) and G(2)) which have been recorded in dichromated gelatin at high exposure energies. As a consequence of material nonlinearities, a third grating G(3) , which has a spatial frequency equal to the difference of the two primary recordings, is also recorded. The model assumes multiple interactions between each of the three gratings and is used to match experimental data where the recording angles were (a) far apart so as to minimize interactions and (b) close together to enhance grating interactions. Good theoretical agreement was found with experiment for both cases. PMID- 20582060 TI - Holographic evaluation of ceramic materials. AB - The coherent optical technique of holographic correlation is applied to the nondestructive evaluation of ceramic materials. A Fresnel correlator is used to holographically construct a matched filter to a small test area on the surface of a silicon nitride ceramic. The subsequent change in correlation signal intensity, from localized microstructural changes occurring on the ceramic surface, is determined as the sample is subjected to thermal stress. A novel method to detect and quantify any loss in correlation signal strength arising from the bulk movement of the ceramic sample within its support is described. Results are presented which show that the correlation technique is capable of evaluating the characteristics of ceramic materials in terms of their response to thermal stress. PMID- 20582061 TI - Time resolved imaging through a highly scattering medium. AB - Transmission images through a highly scattering medium have been obtained using picosecond pulses of visible light. The imaging method involves recording and discriminating between the times-of-flight of photons that penetrate th medium and using a fraction of the light with the shortest travel times to construct an image. The technique is being developed as a possible alternative method of screening for breast cancer without using potentially harmful x-rays. One- and two-dimensional images are presented of objects whose optical thicknesses are comparable with those of the human breast at visible wavelengths. PMID- 20582062 TI - Resolution experiments using the white light speckle method. AB - Noncoherent light speckle methods have been successfully applied to gauge the motion of glaciers and buildings. Resolution of the optical method was limited by the aberrating turbulent atmosphere through which the images were collected. Sensitivity limitations regarding this particular application of speckle interferometry are discussed and analyzed. Resolution limit experiments that were incidental to glacier flow studies are related to the basic theory of astronomical imaging. Optical resolution of the ice flow measurement technique is shown to be in substantial agreement with the sensitivity predictions of astronomy theory. PMID- 20582063 TI - Aberration corrected aspheric gratings for far ultraviolet spectrographs: conventional approach. AB - Two approaches to reducing optical aberrations of concave grating spectrographs have been used, holographically controlling the groove curvature and spacing and reshaping the optical substrate while ruling the grooves conventionally. The latter approach, slightly deforming an ellipsoidal grating blank, can lead to diffractionlimited performance at a single far ultraviolet wavelength. When such a grating is used in a slitted Rowland circle spectrograph, the result is an extremely efficient spectrograph with spectral resolving power of approximately 30,000 and low astigmatism. Optical fabrication technology has advanced to the point where these exotic surface gratings are becoming practical. PMID- 20582064 TI - Application of Kogelnik's two-wave theory to deep, slanted, highly efficient, relief transmission gratings. AB - Deep photoresist gratings, slanted as well as unslanted, were produced holographically in clear Shipley 1400 photoresist. The diffraction efficiencies of these gratings were measured as a function of incident angle for three wavelengths with polarization perpendicular to the plane of incidence. It is shown that the results agree fairly well with those predicted by Kogelnik's two wave theory, indicating that these relief gratings behave like volume holograms. An explanation in terms of thin and thick gratings is given, and practical conclusions are drawn from these observations. PMID- 20582065 TI - Retroreflector using gradient-index rods. AB - A gradient-index rod whose length is a quarter of the periodic length works as a retroreflective element when its endface is coated with metal. This paper describes the experiment and theory on the reflectivity of such a rod and that of an array comprising seven or nineteen rods when they are illuminated by a Gaussian laser beam. We clarify how the reflectivity depends on the offset of the beam axis and the inclination angle of the axis. The far field pattern of the reflected wave is also investigated. PMID- 20582066 TI - Wavefront aberration correction analysis of an all-holographic straight-line scanner. AB - This paper describes an all-holographic straight-line scanner consisting only of a holographic disk and a holographic lens. Scanning beam aberration correction was extensively analyzed using diffraction theory. A new technique for simultaneously optimizing the phase transfer functions of these two holograms is proposed, and a method to construct these two holograms using holographic recording is discussed. This technique led to a compact, high resolution holographic line scanner with a 1/e(2) scanning beam spot size of 100-120 microm for a scanning width of 252 mm. The radius of the disk at the center of illumination is only 28 mm. PMID- 20582067 TI - Actuator influence functions of active mirrors. AB - A method for calculating the actuator influence functions of an active mirror is described. The method is based on a model of the mirror as a thin plate attached by actuators to a very stiff reaction structure. Arbitrary actuator layouts can be handled. The mirror deflections calculated agree well with the results of a finite element analysis of the structure. PMID- 20582068 TI - Two-step regression procedure for the optical characterization of thin films. AB - A diode array rapid scan spectrometer is used for measuring the intensity of polychromatic light in the 300-420-nm range reflected from a diamondlike carbon film as a function of wavelength. With a fixed grating setting, the wavelength range of 120 nm can be covered in 23 ms. From the reflected intensity, a new two step regression procedure is utilized to determine refractive index, bandgap, slope of the absorption edge, and film thickness. The calculated parameters are independent of the starting set and the sequence of parameter estimation. The accuracy of the regression procedure is verified by comparison to the envelope method. It is shown using simulated data that, for strongly absorbing films, the new regression procedure is more accurate than the envelope method. The new regression method can handle very noisy reflectance spectra also. PMID- 20582069 TI - Evolution of thermochromism during oxidation of evaporated vanadium films. AB - Thin vanadium oxide films were made by vacuum evaporation followed by the annealing posttreatment in the presence of air. The thickness increased by a factor as large as approximately 2.3 on oxidation. Electron diffractograms indicated a bcc ? monoclinic transformation during the annealing, and electron micrographs showed pronounced grain growth. Temperature-dependent electrical conductivity as well as spectral transmittance was measured vs annealing time. At an initial thickness of 0.12 microm, it took a few hours to establish VO(2) films with a well defined semiconductor-metal transition and concomitant thermochromic switching at approximately 57 degrees C. PMID- 20582070 TI - Oil UV extinction coefficient measurement using a standard spectrophotometer. AB - This paper investigates the possible techniques for measurement of the extinction coefficient of oils in the near UV. Results show that the best technique, in precision and ease of use, is the unknown thickness method. This method, never proposed up to now as far as we know, allows the use of a standard spectrophotometer. Beer's law is also validated for oils and a simple function is proposed for fitting the extinction coefficient spectra. PMID- 20582071 TI - Matrix description of radiometric quantities. AB - The impetus for this paper was to assist investigators not familiar with radiometry theory. Many times they apply a scalar theory to the scattering of polarized light from nondepolarizing targets. Also some investigators erroneously apply a combined scalar-vector theory since the correct vector-matrix approach has not been developed in the literature. The classical theory used by many investigators is modified in vector-matrix form in this paper. The vector-matrix theory is applied to the various geometries. These results and examples are presented in tabular form. PMID- 20582072 TI - Microfabricated incandescent lamps. AB - A silicon filament vacuum sealed incandescent light source has been fabricated using IC technology. The incandescent source consists of a heavily doped p(+) polysilicon filament coated with silicon nitride and enclosed in a vacuum sealed ( approximately 80-mT) cavity in the silicon chip surface. The filament is electrically heated to reach incandescence at a temperature near 1400 K. The power required to achieve this temperature for a filament 510 x 5 x 1 microm(3) is 5 mW yielding a total optical power of 250 microW with a peak distribution wavelength near 2.5 microm. The radiation emitted by this source approximately follows Lambert's cosine law. The energy conversion efficiency is 5%. PMID- 20582073 TI - Electrooptic detector of temporally coherent radiation. AB - This paper presents a nonmechanical method of measuring temporally coherent light which may be dominated by incoherent background radiation. To obtain detection in the presence of high levels of incoherent radiation, the detector must reject constant and fluctuating contributions due to incoherent light. Extreme sensitivity of the method derives from preferentially modulating the coherent light in such a way that the exact periodicity of the resulting detected signal component is known, permitting, in principle, processing gains which are almost arbitrarily large. Wavelength estimates are also obtained, even when the coherent source power is orders of magnitude less than the power of background radiation. The approach lends itself to rugged and easily constructed implementation. This paper then provides an in-depth noise analysis of the general approach. Numerical examples are also given. Results of a crude laboratory test are presented. Although limited by shortcomings of the components at hand, the experim ent demonstrated easy measurement of coherent radiation >40 dB below the ambient incoherent light and discernible output at a signal-tointerference level of -53 dB. PMID- 20582074 TI - Generalized photodiode self-calibration formula. AB - We have derived the photodiode self-calibration formula for calculating the internal quantum efficiency of silicon photodiodes from the results of one, two, or three independent self-calibration experiments and from the results of the oxide bias and reverse bias experiments in conjunction with a calculation of the effect of Auger recombination. We show that the formula published elsewhere for these three effects is not correct. PMID- 20582075 TI - Parameters of spinning FM reticles. AB - The literature describes tracking devices that allow a single detector coupled to a spinning FM reticle to determine target location. The spinning FM reticles presented were limited to single parameter reticles of frequency vs angle, frequency vs radius, or phase. This study presents these parameters with their capabilities and limitations and shows that multiple parameters can be integrated into a single reticle. Also, a general equation is developed that describes any FM reticle of the spinning type. PMID- 20582076 TI - Applied optics. PMID- 20582077 TI - Information for contributers. PMID- 20582078 TI - Patents. AB - 4,922,497; 4,932,739; 4,936,660; 4,946,264; 4,948,212; 4,948,959; 4,950,042; 4,950,044; 4,958,892; 4,946,253; 4,955,694; 4,961,615; 4,960,311; 4,961,621; 4,962,987; 4,968,126. PMID- 20582079 TI - Applied optics of optics and opticists. PMID- 20582080 TI - Smart Quasiserial post processor for optical systolic systems. AB - A novel quasiserial post processor is proposed for improving the performance of optical systolic systems. PMID- 20582081 TI - Fresnel zone approach to self-Fourier transforming. AB - The phenomenon of self-imaging and (in the case of coherent illumination) self Fourier transforming was first observed over a century and a half ago. [H. Talbot, "Facts Relating to Optical Science NoIV.," Philos. Mag. 9,403-407 (1836).] There has since been a steady stream of publications in which the phenomenon has been noted and a theoretical analysis presented. Most noteworthy of these papers in recent years have been those by Kolodziejczyk, Kalestynski, and Smolinska. [A. Kolodziejczyk, "Realization of Fourier Images Without Using A Lens By Sampling The Optical Object," Opt. Acta. 32, 741-746 (1985); and A. Kalestynski and B. Smolinska, "Multiple Image Formation By Sampling Fraunhoffer Diffraction Patterns," Opt. Acta. 24,1115-1124 (1977).]. PMID- 20582082 TI - Optical disk based joint transform correlator. AB - A joint transform correlation system based on optical disks is presented. The operation principle, system considerations, and processing speed are discussed. PMID- 20582083 TI - Parallel algorithms based on expander graphs for optical computing. AB - We consider the task of interconnecting processors to realize efficient parallel algorithms. We propose interconnecting processors using certain graphs called expander graphs, which can provide fast communication from any group of processors to the rest of the network. We show that these interconnections would result in a number of efficient parallel algorithms for sorting, routing, associative memory, and fault-tolerance networks. As the interconnections based on expander graphs are global and irregular, we reason that optical interconnections are preferred to electronic and propose implementation of these interconnections using the programmable optoelectronic multiprocessor architecture. PMID- 20582084 TI - Resource requirements for digital computations on electrooptical systems. AB - In this paper we study the resource requirements of electrooptical organizations in performing digital computing tasks. We define a generic model of parallel computation using optical interconnects, called the optical model of computation (OMC). In this model, computation is performed in digital electronics and communication is performed using free space optics. Using this model we derive relationships between information transfer and computational resources in solving a given problem. To illustrate our results, we concentrate on a computationally intensive operation, 2-D digital image convolution. Irrespective of the input/output scheme and the order of computation, we show a lower bound of ?(nw) on the optical volume required for convolving a w x w kernel with an n x n image, if the input bits are given to the system only once. PMID- 20582085 TI - Implementation of trinary logic in a polarization encoded optical shadow-casting scheme. AB - The design of various multioutput trinary combinational logic units by a polarization encoded optical shadow-casting (POSC) technique is presented. The POSC modified algorithm is employed to design and implement these logic elements in a trinary number system with separate and simultaneous generation of outputs. A detailed solution of the POSC logic equations for a fixed source plane and a fixed decoding mask is given to obtain input pixel coding for a trinary half adder, full adder, and subtractor. PMID- 20582086 TI - Optical programmable cellular logic array for image processing. AB - An optical parallel architecture is suggested to implement a basic programmable cellular logic array for image processing. Interconnection of the neighboring cells is achieved by using an optical correlator. The required parallel logic gates are executed with spatial coding and electronic thresholding methods. Another optical correlator is used to spatially code the outputs from the 2-bit decoder array of shadowgrams. The optical method for the directional interconnection is also discussed. An image processing example is simulated and verified experimentally. PMID- 20582087 TI - Signal prediction by an optically controlled neural network. AB - Networks of interconnected nonlinear analog processors, or neurons, are finding increasing use in adaptive problems. Adaptive signal prediction has been widely used for many years but has been primarily restricted to linear systems and signals, for which the mathematical treatment of the problems is tractable. We present results using an optically controlled adaptive neural network for nonlinear signal prediction. PMID- 20582088 TI - PHIND: an analytic model to predict target acquisition distance with image intensifiers. AB - An earlier developed calculation scheme to predict the visual range with image intensifiers is further elaborated and quantified. On the basis of the physical characteristics of the image intensifier and the observation conditions (target size and contrast and the meteorological visual range), the recognition distance for any value of the vertical illuminance can be calculated. The predictions were verified with a sizable experimental data set. The recognition distance for widely varying targets could be described on the basis of realistic physical target contrasts with respect to background and of a characteristic size which may be related to typical background clutter. PHIND FORTRAN and pocket calculator programs are available on request. PMID- 20582089 TI - Binary nonlinear joint transform correlation with median and subset median thresholding. AB - We investigate the performance of the binary joint transform correlator (JTC) for three types of thresholding used to binarize the joint power spectrum. The first thresholding method uses the median of the joint power spectrum of the reference image, which is independent of the effect of input scene noise. The second thresholding method uses the median of the joint power spectrum of the input scene and the reference image. The third method is the subset median thresholding. The subset median is computed for each segment of the joint power spectrum and is used to threshold the same segment. The threshold computed by the second or third method is dependent on the effect of the input scene noise. The correlation performance of the binary JTC is determined for each thresholding method and is compared with the linear (conventional) JTC. Computer simulation is used to determine the correlation peak intensity, peak-to-sidelobe ratio, and correlation width for various thresholding techniques. The results indicate that the thresholding of the joint power spectrum using the methods that take into account the input scene noise produces a reasonably good correlation performance. PMID- 20582090 TI - Analysis of transient emission curves by a convolved autoregressive model. AB - A new method is developed for estimating the decay parameters of transient emission curves convolved with an instrumental response function. This method is based on the convolved autoregressive model, which we originally proposed. The computation time of the method is much shorter than that of the conventional nonlinear least-squares method. Results of analyses for simulated and real data are shown to demonstrate a high potential of the developed method. PMID- 20582091 TI - Optical random number generator based on photoevent locations. AB - A 2-D position-sensitive photon-counting detector is used in an optical random number generator in which the locations of detected photoevents provide the random numbers. The spatial distribution of photoevent locations is dictated by imaging a control object onto the detector. An iterative calibration procedure is used to determine the brightness distribution of the control object. Two control objects were examined-film and a video monitor. With both control objects, the performance of the optical random number generator approached that of pseudorandom number generators. PMID- 20582092 TI - Applied optics. PMID- 20582093 TI - Nasa patter. PMID- 20582095 TI - Improved precision of single-shot temperature measurements by broadband CARS by use of a modeless laser. AB - The use of a novel modeless laser as the broadband source in multiplex CARS thermometry, by reducing the laser noise on the CARS spectra, is shown to give a precision of approximately 1 % in single-shot temperature measurements in nitrogen at 1200 K. PMID- 20582096 TI - Suppression of laser spiking by intracavity second harmonic generation. AB - Laser spiking in a long pulse Nd:YAG laser has been substantially suppressed by intracavity second harmonic generation with very little loss of laser pulse energy. PMID- 20582097 TI - Stark-cell stabilized submillimeter wave laser at 393 mum. AB - We report new Stark resonances in methylene fluoride on the R18 line of the 9.4 microm CO(2) laser transition. These resonances are used to stabilize an optically pumped formic acid laser at 393 microm. PMID- 20582098 TI - Single frequency operation of an injection-seeded Nd:YAG laser in high noise and vibration environments. AB - We report on an experimental demonstration of single frequency operation of an injection-seeded Nd:YAG laser in a high noise and vibration environment. PMID- 20582099 TI - Wavelength tunability of electrooptically tuned Fabry-Perot filters. AB - This work clarifies that the tuning sensitivity of an electrooptically tuned Fabry-Perot filter largely depends on the piezoelectric and dielectric constants as well as the electrooptic coefficient. PMID- 20582100 TI - Multiple line and polarization control in a far infrared laser with a compound grating resonator. AB - Operating principles and the efficacy of two types of coupled laser resonator are described and their experimental verification presented: a compound mirror grating-mirror resonator (MGM), and a mirror-grating-grating resonator (MGG). The coupling for both resonators is through the zero-order diffraction of the resonator's primary grating. The coupling mechanism makes it possible to obtain a particular wavelength and polarization from the resonators. Since the phase change of the radiation diffracted into both first order and zero order is different for the radiation polarized linearly parallel and linearly perpendicular to the direction of the grating lines, a different effective length of the secondary cavity exists for the two polarizations. In the case of the MGM resonator, the coupling is used to control the polarization properties of a single laser line. For the MGG resonator, the coupling is used so that two distinct laser lines can lase simultaneously. The MGG resonator also has a degree of control of the relative polarization of the two lines. The resonators are used to control the degree of the laser output coupling, output radiation polarization, and resonator bandwidth. The resonators were used for interaction studies between four pairs of water vapor lines (26.60-47.47, 26.60-47.70, 27.97 47.47, and 27.97-47.70, microm). PMID- 20582101 TI - First-order sources in first-order systems: second-order correlations. AB - The laws of propagation of the second-order correlation of a generalized Gaussian Schell-model source in first-order systems are deduced from the canonical operator formalism. A far-reaching generalization of Kogelnik's q parameter is derived, valid in n dimensions, for misaligned, lossy, and anisotropic sources and systems. Even in one dimension these results extend previous findings. The degree of global coherence is generalized and shown to be an invariant in n dimensions for anisotropic lossless systems. A new invariant, the degree of ripple, is found for a special class of lossy first-order system, which includes the Gaussian aperture. PMID- 20582102 TI - Strain and scattering related spectral output of 1.3microm InGaAsP semiconductor diode lasers. AB - A correlation between the spectral output of 1.3 microm InGaAsP semiconductor diode lasers and the distribution along the length and width of the active region of strain and scattering centers is reported. The strain and scattering center distributions in the active region were obtained by measuring and analyzing the spatially resolved and polarization resolved electroluminescence along the active region of the lasers. Measurements were made on gain-guided, planar buried heterostructure, and arrowhead buried crescent lasers. The results suggest that the material properties of the laser structure affect the longitudinal mode spectrum. PMID- 20582103 TI - Mode-locked laser pulse train repetition frequency multiplication: the optical rattler. AB - We present a simple method for multiplying the pulse repetition frequency of a given cw mode-locked laser. We report, in particular, the doubling and tripling of the c/2L frequency of a synchronously pumped mode-locked dye laser. This technique should prove useful for a variety of ultrashort pulse applications including high repetition rate optical pulse amplification studies, electronic and optical material characterization, optical chaos experiments, and impulsively driven spectroscopy. PMID- 20582104 TI - Effect of bending on zero dispersion operation of single-mode optical fibers. AB - Perturbation theory for bent optical fibers predicts that the unperturbed (straight) propagation constant (or effective index) will be corrected by a small term that is proportional to (R(b))(-2), where R(b) is the radius of the bend. We examine how this small correction affects the chromatic dispersion of the fundamental mode, and in particular we examine the changes that occur when the fiber operates at the zero dispersion wavelength lambda(o). For a bend radius of 1 cm, lambda(o) may shift by up to 20 nm. PMID- 20582106 TI - Incident polarization angle and temperature dependence of polarization and spectral response characteristics in optical fiber couplers. AB - The incident polarization angle and temperature dependence of the polarization and spectral response characteristics of three different types of fiber coupler are presented. The couplers are (1) the biconicalfused- twisted-taper single-mode fiber (coupler A), (2) the asymmetric-etched-fused-taper wavelength division multiplex (coupler B), and (3) the biconical-polished polarization maintaining fiber (coupler C), respectively. It is confirmed experimentally that the polarization characteristics of couplers A and B vary greatly with temperature, but those of coupler C are independent of temperature. Also, the wavelength dependence characteristics of the power splitting ratio of couplers B and C have almost no change with temperature. However, the wavelength dependence of coupler A is greatly changed with temperature. Comparing couplers A and B, it is postulated that the sinusoidal variations of the polarization state vs the incident polarization angle are due to the stress birefringence caused by the fiber twisting when the fused fiber coupler is fabricated and packaged. PMID- 20582105 TI - Power-by-light systems and their components: an evaluation. AB - This paper describes the testing of small sized systems and their components that use power-by-light (PBL) to transfer energy across a barrier. The PBL systems used improved high power laser diodes, large numerical aperture fibers, improved high efficient, high power solar cells, and low input-to-high output voltage dc dc converters. The laser diodes emitted up to 3.6 W continuously by converting approximately 40% of its electrical power to light power into fibers that transmitted up to 92% of its incident energy flux. The specially fabricated solar cell converted 46% of its incident light power to electrical power at a fill factor of 89%. The most efficient 100- and 220-mJ PBL systems charged capacitors in 0.64 and 0.8 s for a total system efficiency of 3.4 and 5.5%. Expected improvements could yield system efficiencies of 12%. PMID- 20582107 TI - Phase-modulated fiber optic gyroscope with wide dynamic range and linear scale factor. AB - An open-loop phase-modulated fiber optic gyroscope with a wide dynamic range and linear scale factor is described. The optical Sagnac phase shift is transposed into an electrical phase shift by introducing two phase sensitive detectors and two electronic amplitude modulators with independent carrier frequency from the optical phase modulation. Preliminary experiments show good linearity over a wide dynamic range up to 1000 degrees /s and verifies the theoretical prediction. PMID- 20582109 TI - Waveguide optical isolator: a new design. AB - A new design of a thin film waveguide optical isolator is described. It is composed of a nonreciprocal mode converter by the Faraday effect, a reciprocal mode converter by the Cotton-Mouton effect, an integrated mirror, and TE-mode selectors. Its mode transfer matrices are derived. Numerical calculations show that wider tolerances of the film parameters and smaller dimensions are obtained compared with the ordinary tandem type waveguide isolators without the integrated mirror. This structure is free of the problem of the localized control of the directions of the magnetization, which has been required for the ordinary tandem type waveguide isolator. PMID- 20582108 TI - TiO(2)-SiO(2) based glasses for infrared hollow waveguides. AB - Hollow core waveguides made of TiO(2)-SiO(2) based glasses have been proposed for the IR. A series of TiO(2)-SiO(2) based glasses were prepared and their complex refractive indices measured by reflectometry. Using measured refractive indices, we calculated spectral losses of the TiO(2)-SiO(2) hollow waveguides. With the waveguides, we can expect efficient transmission of mid-IR light including CO(2) laser light, since refractive indices of the glasses become less than unity and the absorption coefficients become small in the 8-11-microm wavelength range. PMID- 20582110 TI - Water vapor effects on optical characteristics in Ti:LiNbO(3) channel waveguides. AB - This paper describes experimental studies on propagation loss and crosstalk of TM polarized light in Ti-diffused Z-cut LiNbO(3) channel waveguides as a function of the water vapor content in the diffusion atmosphere. The dependence of surface roughness and crystal quality on the waveguide fabrication atmosphere is taken into consideration. In this study it is found that waveguides with low propagation loss (<0.2 dB/cm), low crosstalk (<-20 dB), and smooth surfaces can be fabricated by strictly controlling the water vapor content introduced into the oxygen or argon carrier gas. PMID- 20582111 TI - Integrated optic array illuminator: a design for efficient and uniform power distribution. AB - A design principle for an integrated optic array illuminator is presented, and an array illuminator which can generate uniform beams with 100% power efficiency has been designed. It was found that there exists a trade-off relationship between the beam compression ratio and the maximum number of beams available. Based on this relationship, the possibility and limitation of the proposed scheme are discussed. PMID- 20582112 TI - Achromatic waveguide input/output coupler design. AB - An investigation into methods for achromatizing the coupling angle characteristics of waveguide input/output couplers is described. The basic approach involves correcting the inherent angular dispersion of conventional waveguide couplers with a diffraction grating. Two configurations are analyzed in detail: a hybrid prism/grating coupler and a double grating coupler. Expressions are derived for values of the grating parameters that produce achromatic coupling. A method is also presented to predict the achromatic wavelength range and maximize it with the available degrees of freedom. For a coupling angle tolerance of 0.005 degrees , it is found that with double grating couplers achromatic wavelength ranges of the order of 10 nm can be obtained, and that with prism/grating couplers this range can be as large as 200 nm. PMID- 20582113 TI - Finite difference solution for graded-index cylindrical dielectric waveguides: a scalar wave approximation. AB - A simple numerical method based on finite differences to solve the scalar wave equation encountered in optical fibers is presented. The method uses the Ricatti transformation to the scalar wave equation and is capable of analyzing fibers of arbitrary refractive index profiles. Achieving errors as low as 0.005% for propagation constants is possible for lower-order modes. However, the error seems to increase for frequencies closer to cutoff. PMID- 20582114 TI - Linear simultaneous solution for temperature and absorbing constituent profiles from radiance spectra. AB - A linear form of the radiative transfer equation (RTE) is formulated for the direct and simultaneous estimation of temperature and absorbing constituent profiles (e.g., water vapor, ozone, methane) from observations of spectral radiances. This unique linear form of the RTE results from a definition for the deviation of the true gas concentration profiles from an initial specification in terms of the deviation of their effective temperature profiles from the true atmospheric temperature profile. The effective temperature profile for any absorbing constituent is that temperature profile which satisfies the observed radiance spectra under the assumption that the initial absorber concentration profile is correct. Differences between the effective temperature, derived for each absorbing constituent, and the true atmospheric temperature are proportional to the error of the initial specification of the gas concentration profiles. The gas concentration profiles are thus specified after inversion of the linearized RTE from the retrieved effective temperature profiles assuming that one of the assumed concentration profiles is known (e.g., CO(2)). Because the solution is linear and simultaneous, the solution is computationally efficient. This efficiency is important for dealing with radiance spectra containing several thousand radiance observations as obtained from current airborne and planned future spaceborne interferometer spectrometer sounders. Here the solution is applied to spectral radiance observations simulated for current filter radiometers and planned spectrometers to demonstrate the anticipated improvement in future satellite sounding performance as a result of improved instrumentation and associated sounding retrieval methodology. PMID- 20582115 TI - Pressure, temperature, and ozone profile retrieval from simulated atmospheric earthlimb infrared emission. AB - A method is presented for retrieving pressure, temperature, and ozone mixing ratio profiles from multilevel high resolution earthlimb emission data taken in the spectral region near the CO(2)Q-branch at 791.5 cm(-1). Theory is developed for the construction of a retrieval algorithm which brings the magnitudes of calculated and measured CO(2) and O(3) features into agreement by adjusting a hydrostatic trial atmosphere having one fixed reference pressure. It is shown that overlap between the CO(2) and O(3) features can be used to determine the correct reference pressure. The method is examined using simulations to demonstrate the retrieval of vertical profiles of pressure, temperature, and ozone mixing ratio in the stratosphere. Numerical studies of the effects of uncertainties in line parameters and instrument calibration errors are also presented. PMID- 20582116 TI - Backscattering, extinction, and liquid water content in fog: a detailed study of their relations for use in lidar systems. AB - A solution to the single-scattering lidar equation to infer optical extinction, liquid water content W, and visibility in a fog through a monostatic pulsed lidar, requires the use of the relations, and combinations of them, between backscattering coefficient beta, extinction coefficient sigma, and W. To this end, beta and sigma have been computed for 239 droplet size spectra and forty wavelengths from 0.25 to 12 microm, together with W, and the three relations beta vs sigma, W vs sigma and sigma(0.55 microm) vs sigma have been determined. The analysis of their behavior with wavelength shows that (1) the relation beta vs sigma is mostly reliable in the lambda = 0. 25-2-microm region, where the dispersion of the beta values around the best-fit curve is within 20%; (2) the relation W vs sigma is generally not well verified (the dispersion is centered around 30%), and when used in connection with the beta vs sigma relation to infer liquid water content, their joint dispersion P(D) is always greater than 20%; (3) the relation sigma(0.55 microm) vs sigma is well verified in the region lambda = 0.25-2 microm (dispersion within 15%), and when used in connection with the beta vs sigma relation to infer visibility P(D) appears to be minimum at lambda congruent with 0.35 microm (P(D) = 4.7%). PMID- 20582118 TI - Relinquishing the reins. PMID- 20582117 TI - Scattering from arbitrarily shaped particles: theory and experiment. AB - A numerical implementation of the volume integral equation formulation of electromagnetic scattering is used to calculate the scattered intensity of various particles. The numerical method has the capability of determining the scattering by arbitrarily shaped and inhomogeneous scatterers. Results of calculations are presented for scatterers which have not only a size comparable to the wavelength of the incident radiation but are also irregular and inhomogeneous. The theoretical results are compared to microwave analog measurements performed at the microwave facility of the Space Astronomy Laboratory (ISST). It is found that experiment and theory agree well. The accuracy and versatility of the numerical method and the analog measurements are illustrated. Finally, the advantages and disadvantages of the numerical method are discussed. PMID- 20582119 TI - Patents. AB - 4,959,559; 4,960,315; 4,964,705; 4,964,706; 4,969,737; 4,966,431; 4,968,112; 4,971,411; 4,971,413; 4,969,699; 4,973,838; 4,969,720; 4,973,112; 4,973,121. PMID- 20582120 TI - Ultraviolet/ozone cleaning of a soft x-ray grating contaminated by synchrotron radiation. PMID- 20582121 TI - Modified electronic speckle pattern interferometer employing an off-axis reference beam. AB - A new arrangment for an electronic speckle pattern interferometer is reported in which an off-axis reference beam is used, thereby eliminating alignment problems. PMID- 20582122 TI - Variable angle, fixed position, beam alignment device. AB - We describe a general beam alignment device that allows variation of the angle of incidence while preserving the position of incidence on a sample. PMID- 20582123 TI - Subtractive Moire technique for evaluating the wedge angle of a beam splitter. AB - This Technical Note describes a method to measure the wedge angle of a beam splitter that relies on shear interferometry and the moire phenomenon. PMID- 20582124 TI - High resolution photoacoustic spectra of Ho(3+) and Er(3+) in chloride hexahydrate matrix. AB - High resolution photoacoustic spectra of Ho(3+) and Er(3+) are reported for their chloride hexahydrates. PMID- 20582125 TI - Temperature dependence of the Verdet constant in several diamagnetic glasses. AB - Measured temperature dependences of the Verdet constants of SiO(2), SF-57, and BK 7 are approximately 10(-4)/K within 3-20% of Becquerel formula estimates. PMID- 20582126 TI - Confocal compact scanning optical microscope based on compact disc technology. AB - A compact scanning optical microscope (SOM) based on the optics and the mechanics of a compact disc (CD) player has been constructed. The low weight and compact construction of a CD player offer the possibility of scanning the entire microscope with respect to a stationary object. The compact scanning optical microscope is capable of measuring object-induced amplitude and phase changes of the light and is equipped with automatic focusing. The laser in the CD player is replaced by the endface of a single-mode fiber. The end face of the fiber acts both as the emitting source and as a point detector. Thus confocal detection is obtained without the problem of positioning a point detector with respect to a point source. PMID- 20582127 TI - Analysis of confocal laser-microscope optics for 3-D fluorescence correlation spectroscopy. AB - Quantitative fluorescence correlation spectroscopy (FCS) and fluorescence photobleaching recovery (FPR) measurements in bulk solution require a well characterized confocal laser microscope optical system. The introduction of a characteristic function, the collection efficiency function (CEF), provides a quantitative theoretical analysis of this system, which yields an interpretation of the FCS and FPR measurements in three dimensions. We demonstrate that when the proper field diaphragm is introduced, the 3-D FCS measurements can be mimicked by a 2-D theory with only minor error. The FPR characteristic recovery time for diffusion is expected to be slightly longer than the corresponding time measured by FCS in the same conditions. This is because the profile of the laser beam used for photobleaching is not affected by the field diaphragm. The CEF is also important for quantitative analysis of standard scanning confocal microscopy when it is carried out using a finite detection pinhole. PMID- 20582128 TI - Real time bleaching of methylene blue or thionine sensitized gelatin. AB - The kinetics of bleaching of methylene blue or thionine sensitized gelatin plates are investigated with a singlebeam exposure experiment. It is found that thionine bleaching can be modeled by a first-order theory; whereas, a higher-order theory is found necessary to explain methylene blue bleaching. PMID- 20582129 TI - Processing of holographic AgBr films studied by x-ray fluorescence analysis. AB - The feasibility of using x-ray fluorescence techniques to determine the concentrations of silver, bromine, and iodine in silver halogenide holographic films is studied. A small apparatus employing a 30-mCi (57)Co radioactive source and a germanium photon detector is described. AgBr films were exposed to different amounts of light and subjected to several types of chemical processing, and their silver and halogen contents were investigated. In addition, the relationship between the concentration of absorbing silver in the emulsion and its optical density was determined. PMID- 20582130 TI - Interferometric scanning acoustooptic spectrum analyzer. AB - An interferometric scanning acoustooptic (AO) spectrum analyzer is described. The instantaneous detector array is replaced by an AO Bragg cell driven by a short rf pulse and a single fast photodetector, and the diffracted beam is mixed with a local oscillator. The temporal modulation of the heterodyne signal gives the spectrum of the input signal with linear characteristics. Using this architecture, a dynamic range of 70 dB can be achieved with a large time bandwidth product (1000) and high speed (50 micros/spectrum). PMID- 20582131 TI - Thermally stable field compensated Michelson interferometer for measurement of temperature and wind of the planetary atmospheres. AB - A Michelson interferometer has been built to measure the wind and temperature in the earth's upper atmosphere using nightglow emissions from atomic oxygen and radical OH. The interferometer uses field compensation to give large geometric etendu allowing measurements with emission lines of intensity of approximately 30 R at zenith. For wind measurement, it is thermally stabilized permitting operation without difficulty. The instrument incorporates calibration sources allowing temperature and wind measurements. It is operated at the Observatoire de Haute-Provence (43 degrees 56'N, 5 degrees 43'E, France) in summer and Sodankyla (67 degrees 22'N, 26 degrees 38'E, Finland) in winter. Its performance is illustrated by some examples of measurements and results. PMID- 20582132 TI - Laser interferometric thermometry for substrate temperature measurement. AB - This paper investigates a simple noncontact optical thermometry technique based on the laser interferometric measurement of the thermal expansion and refractive index change of a thin transparent substrate or temperature sensor. The technique is shown to be extendible from room temperature to at least 900 degrees C with the proper choice of a thermally stable sensor. Sensor materials investigated included c-axis A1(2)O(3), MgO, MgAl(2)O(4) (spinel), Y(2)O(3)-ZrO(2) (yttria stabilized zirconia), and fused silica. Calibration data were taken at 633 nm by measuring the sensor response to known temperature changes. These data provided (1) the information needed for quantitative thermometry (i.e., the functional relationship between interference fringes and temperature for samples of known thickness) and (2) the thermal coefficient of refractive index for those materials with known thermal expansion coefficients. PMID- 20582133 TI - Surface figure measurements of radio telescopes with a shearing interferometer. AB - A new technique for determining the surface figure of large submillimeter wavelength telescopes is presented, which is based on measuring the telescope's focal plane diffraction pattern with a shearing interferometer. In addition to the instrumental theory, results obtained using such an interferometer on the 10.4-m diam telescope of the Caltech Submillimeter Observatory are discussed. Using wavelengths near 1 mm, a measurement accuracy of 9 microm, or lambda/115, has been achieved, and the rms surface accuracy has been determined to be just under 30 microm. The distortions of the primary reflector with changing elevation angle have also been measured and agree well with theoretical predictions of the dish deformation. PMID- 20582134 TI - Time reconstructions in light-in-flight recording by holography. AB - When light-in-flight recording by holography is used two different sorts of apparent distortion of the wavefronts exist. The first distortion is common to all types of ultrafast gating viewing system and like relativistic phenomena it is caused by the limited speed of light used for observation. The second distortion is produced by the holographic process itself and is caused by the limited speed of the light pulse used as a reference beam. By using the second distortion to compensate for the first it is possible to manipulate or eliminate apparent wavefront tilts or distortions so that measurement of the 3-D shape of wavefronts or other objects is facilitated. A reconstruction beam that is the conjugate of the reference beam results in three interesting effects, one of which is the reemission of the recorded pulse. PMID- 20582135 TI - Electrostatically driven micromechanical 2 x 2 optical switch. AB - This paper describes a new electrostatically driven micromechanical 2 x 2 optical switch which has advantages in terms of its small size and low driving power. Insertion losses, which are important to the fabrication of a low loss switch, are theoretically and experimentally evaluated. Based on the results, the relationship between cross angle and gap length is obtained in order to minimize insertion loss. The switch is demonstrated and its switching performance is examined. Insertion losses of less than 3.1 dB and crosstalk of less than-40 dB were obtained. PMID- 20582136 TI - Determination of basic grids for subtractive moire patterns. AB - The simple formula derived in the paper establishes a direct relationship between moire beat patterns and basic grids for minute displacements. The possibilities of finding a basic grid for a desired moire pattern are pointed out. The analysis is illustrated by several examples of Fresnel moire zone plate patterns and concentric equidistant circular moire patterns obtained by changes of scale and rotation. Possible advantages of the practical use of this element are outlined. PMID- 20582137 TI - Simultaneous temperature and sensitive two-species concentration measurements by single-shot CARS. AB - Simultaneous spatially and temporally resolved measurements of N(2) and O(2) mole fractions and of temperature are performed using coherent anti-Stokes Raman scattering (CARS). The CARS setup is used with the crossed-beam arrangement (BOXCARS) and nonresonant-background suppression. The technique employs two Stokes lasers, broadband and narrowband, in combination with a frequency-doubled Nd:YAG laser. Temperature and N(2) mole fractions are obtained by single-shot multiplex CARS spectra of N(2) using the broadband laser; O(2) mole fractions are deduced from a particular rovibrational Q-line of O(2) using the narrowband dye laser. The single-shot detectivity limit is better than 0.4% for oxygen at 2200 K and atmospheric pressure, i.e., 10(16) molecules x cm(-3). The capability of the technique for measuring 2-D probability density functions is demonstrated in the simple cases of an isothermal jet and a laminar premixed flame of air and ethylene. The experimental work reveals grave difficulties in using CARS for precise measurements of mole fractions: appreciable signals can be created very far from the geometrical focus; beam disruption by turbulence and the Stark effect cause large mole fraction measurement errors. These problems are discussed. Referencing the mole fraction of the second species by nitrogen mole fraction is demonstrated to be a solution for the turbulence effect in premixed flames. PMID- 20582138 TI - Automated measurement method for 360 degrees profilometry of 3-D diffuse objects. AB - An automated measurement method for 360 degrees surface topography of 3-D diffuse objects is presented. The method is based on the simple principle of triangulation with structured illumination. The geometric specifications of the structured light module used in the system are analyzed on a computer. Using an advantageous data acquisition schedule, high data acquisition rates and measuring accuracy can be achieved. The system comprises a structured lighting projector, a 2-D detector array, and a microcomputer for control and processing. Experimental results for 3-D objects are offered. PMID- 20582139 TI - Realization of an infrared spectroradiometer. AB - This paper describes a fully automatic spectroradiometer designed to measure the absolute spectral irradiance of light sources in the 800-2400-nm spectral range by direct comparison of radiation sources with a standard source, both placed the same distance away. The total estimated uncertainty in the comparison process is <1%, which, added to the standard source uncertainty, allows us to obtain the absolute spectral irradiance values of sources in this spectral range with an accuracy of better than 3%. PMID- 20582140 TI - Athermal glass for the infrared. AB - Refractive indices of four CLAP glass systems are measured at room temperature and at higher temperatures in the wavelength range of 0.4-5.5 microm. The coefficients of temperature changes of optical path lengths are calculated and are <1 x 10(-6)/ degrees C in the wavelength range longer than 1microm. This suggests an athermal glass application in the infrared ray region. PMID- 20582141 TI - Carbon arc solar simulator. AB - Measurements of the spatial, spectral, and temporal characteristics of the beam irradiance of a carbon arc solar simulator are reported. Pyroelectric radiometer measurements of total irradiance and spectroradiometer measurements of spectral irradiance are presented. The solar simulator spectral irradiance is compared with the ASTM standard AM 1.5 global solar spectral irradiance over a wavelength region of 300-2500 nm. The suitability of the solar simulator for laser receiver testing is discussed. PMID- 20582142 TI - Ultraviolet conical diffraction: a near-stigmatic tandem grating mounting spectrometer. AB - Conical diffraction grating mounts (gratings used off-plane) offer many new possibilities in the ultraviolet and extreme ultraviolet wavelength domain. Up to now, single conical diffraction gratings, whether coupled or not to grazing incidence gratings, have had limited spectral resolution and disadvantages owing to the simultaneous monochromatic slit image rotation with the grating rotation during the wavelength scan. Here we propose a tandem conical diffraction mount that improves the spectral resolution and nearly eliminates the monochromatic slit image rotation. This results in the improvement of spectral image quality. Through the example of a complete solar telescope-spectrometer instrumentation, the qualities (spectral and angular resolution-2 pm and 1 sec of arc) and limits (lower efficiency) of the mounting are compared to other recent solar instrumentations proposed in the 30-135-nm wavelength range. PMID- 20582143 TI - Optical anisotropy in thin films deposited obliquely: in situ observations and computer modeling. AB - Normal incidence optical anisotropies are monitored during the growth of dielectric and metal films deposited at 45 degrees by logging the quantities R( perpendicular),R( ||), T( perpendicular) and T( ||) as functions of mass thickness d. For both ZrO(2) and Ti(2)O(3), the experimental profile of (R( perpendicular) - R( ||)) vs d is consistent with a refractive anisotropy that remains nearly constant during deposition. Gold, silver, and aluminum (deposited in the absence of oxygen) are shown to exhibit characteristic anisotropy vs d profiles that can be associated with the refractive index resonance in a globular metal film. The anisotropic effects observed in metals, both during deposition and during subsequent argon-ion sputter etching, are modeled by considering the film to comprise a mixture of crystallite-and void-defined materials and by adopting simplified structural hysteresis loops. PMID- 20582144 TI - Assessing Primary Care Physician's Beliefs and Attitudes of Asthma Exacerbation Treatment and Follow-Up. AB - OBJECTIVE: The objective of this survey was to assess adult primary care physicians' and pediatricians' perceptions of asthma exacerbation management, including beliefs concerning the discharge of patients from the emergency department (ED) following asthma exacerbations. METHODS: This was a cross sectional survey of primary care physicians (PCPs) treating adult or pediatric patients. Surveys were mailed to physicians and included questions on how PCPs define an exacerbation, how they are notified and how they followed-up with their patients who experienced exacerbations. RESULTS: A total of 189 physicians were targeted in this survey, with 124 (65%) returning a completed survey. The majority of physicians agreed that an exacerbation included worsening asthma requiring a course of oral corticosteroids (83%). However, >/=70% of physicians agreed that an exacerbation could also include events which did not require OCS. Overall, 71% of PCPs believed that the majority of their patients' asthma exacerbations were treated in the doctor's office with only 6% believing the majority were treated in the ED. Over 90% of PCPs surveyed said they scheduled a follow-up with their patients "all or most of the time" when notified of an ED visit for an asthma exacerbation. Of the adult PCPs surveyed, 20% said they were never notified when one of their patients received treatment in the hospital because of an asthma exacerbation, whereas only 10% of pediatricians said they were never notified. The majority of PCPs surveyed (79%) indicated that if a controller medication was warranted, the ED staff should initiate treatment at time of discharge. CONCLUSIONS: This study showed that healthcare providers may not share a common definition of an asthma exacerbation. In addition, most physicians believe that the majority of exacerbations are treated in their office or at home. Further, most agreed that if a controller medication was warranted, the ED or urgent care staff should initiate treatment. PMID- 20582146 TI - Variability of Carotenoid Biosynthesis in Orange Colored Capsicum spp. AB - Pepper, Capsicum spp., is a worldwide crop valued for heat, nutrition, and rich pigment content. Carotenoids, the largest group of plant pigments, function as antioxidants and as vitamin A precursors. The most abundant carotenoids in ripe pepper fruits are beta-carotene, capsanthin, and capsorubin. In this study, the carotenoid composition of orange fruited Capsicum lines was defined along with the allelic variability of the biosynthetic enzymes. The carotenoid chemical profiles present in seven orange pepper varieties were determined using a novel UPLC method. The orange appearance of the fruit was due either to the accumulation of beta-carotene, or in two cases, due to only the accumulation of red and yellow carotenoids. Four carotenoid biosynthetic genes, Psy, Lcyb, CrtZ 2, and Ccs were cloned and sequenced from these cultivars. This data tested the hypothesis that different alleles for specific carotenoid biosynthetic enzymes are associated with specific carotenoid profiles in orange peppers. While the coding regions within Psy and CrtZ-2 did not change in any of the lines, the genomic sequence contained introns not previously reported. Lcyb and Ccs contained no introns but did exhibit polymorphisms resulting in amino acid changes; a new Ccs variant was found. When selectively breeding for high provitamin A levels, phenotypic recurrent selection based on fruit color is not sufficient, carotenoid chemical composition should also be conducted. Based on these results, specific alleles are candidate molecular markers for selection of orange pepper lines with high beta-carotene and therefore high pro-vitamin A levels. PMID- 20582147 TI - A direct test of the differentiation mechanism: REM, BCDMEM, and the strength based mirror effect in recognition memory. AB - We explore competing explanations for the reduction in false alarm rate observed when studied items are strengthened. Some models, such as Retrieving Effectively from Memory (REM; Shiffrin & Steyvers, 1997), attribute the false alarm rate reduction to differentiation, a process in which strengthening memory traces at study directly reduces the memory evidence for lure items. Models with no differentiation mechanism, such as the Bind-Cue-Decide Model of Episodic Memory (BCDMEM; Dennis & Humphreys, 2001), explain the false alarm rate reduction in terms of the strength of items expected at retrieval. To contrast these explanations, we separately manipulated item strength at encoding and retrieval. Participants studied mixed lists of weak and strong items. Weak items were always presented once. On separate lists, strong items were either presented twice (Strong-2X) or five times (Strong-5X). Within each strength condition, participants completed separate tests with mixed (strong and weak) targets, pure weak targets, or pure strong targets. They were correctly informed of the type of target on each test. Results showed that false alarm rates decreased from the strong-2X condition to the strong-5X condition for the mixed and pure-strong tests, but not for the pure-weak tests. That is, false alarm rates were determined by the strength of targets appearing on the test, not by the content of the study list. The results support BCDMEM's expectation-based explanation and not REM's differentiation-based explanation. PMID- 20582145 TI - Effects of environmental pollutants on the reproduction and welfare of ruminants. AB - Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare. PMID- 20582148 TI - Nicotine addiction in light smoking African American mothers. AB - Although African Americans (AA) smoke fewer average cigarettes per day (CPD) than European Americans (EA), they carry a disproportionate tobacco related morbidity and mortality burden. OBJECTIVE: To evaluate ethnic differences in markers of nicotine addiction, including rates of lifetime nicotine dependence (ND) symptoms, current smoking and smoking during pregnancy across different levels of peak lifetime cigarette consumption. METHODS: Data from 237 EA (N=118) and AA (N=119) mothers participating in the Missouri Family Study (2003-2005), an ethnically diverse family study of offspring outcomes in high and low risk families, were used to contrast prevalence of ND symptoms and other smoking behaviors between EA and AA women at low (1-10 CPD), moderate (11-19 CPD), and high (>= 20 CPD) levels of lifetime peak daily cigarette consumption. RESULTS: Compared with EA smokers, AAs had lower lifetime prevalence of DSM-IV ND (68% v. 54%, p<.05), consumed fewer CPD during their heaviest lifetime consumption (18% EA v. 58% AA smoked <= 10 CPD, p<.0001), but did not differ in overall rates of smoking during pregnancy or current smoking. However, stratifying by categories of peak lifetime daily cigarette use, AA mothers who smoked <= 10 CPD reported greater lifetime ND symptoms and current smoking than their EA counterparts. In addition, nearly two-thirds of AA mothers in this smoking category smoked during pregnancy and 30% smoked throughout an entire pregnancy. The respective prevalence estimates in EA mothers were 38% and 0%. CONCLUSIONS: Stratifying the sample into categories of lifetime peak daily cigarette use revealed significant ethnic/racial differences in smoking prevalence during pregnancy that were obscured in overall analysis. Substantial public health risks warranting clinical attention exist among light smokers, particularly AA women. PMID- 20582149 TI - Immobilization of magnetic iron oxide nanoparticles on laponite discs - an easy way to biocompatible ferrofluids and ferrogels. AB - Magnetic nanocomposites containing iron oxide (maghemite) nanoparticles, well embedded in a synthetic clay matrix (laponite) were prepared by a new one step chemical route and characterized by TEM, XRD, magnetization measurements, Mossbauer spectroscopy, DLS, and MRI measurements. The synthetic procedure leads to non-stoichiometric gamma-Fe(2)O(3) with a controllable content in the nanocomposite. Magnetic nanoparticles incorporated in the diamagnetic clay matrix exhibit a mean diameter of 13 nm, superparamagnetic behavior with a high saturation magnetization achievable at low applied magnetic fields. In-field Mossbauer spectra and ZFC/FC magnetization curves reveal a perfect ferrimagnetic ordering within nanoparticles with negligible spin frustration and interparticle interactions due to the complete coating of maghemite surfaces by the nanocrystalline laponite matrix. Magnetic iron oxide nanoparticles embedded in laponite matrix exhibit strong T(2) weighted MRI contrast. The maghemite/laponite composite particles have 200 nm hydrodynamic diameter and form very stable hydrosols and/or hydrogels depending on their concentration in water. PMID- 20582150 TI - Consistency of Random Survival Forests. AB - We prove uniform consistency of Random Survival Forests (RSF), a newly introduced forest ensemble learner for analysis of right-censored survival data. Consistency is proven under general splitting rules, bootstrapping, and random selection of variables-that is, under true implementation of the methodology. Under this setting we show that the forest ensemble survival function converges uniformly to the true population survival function. To prove this result we make one key assumption regarding the feature space: we assume that all variables are factors. Doing so ensures that the feature space has finite cardinality and enables us to exploit counting process theory and the uniform consistency of the Kaplan-Meier survival function. PMID- 20582151 TI - A Pilot Study of Aerobic Exercise as an Adjunctive Treatment for Drug Dependence. AB - Intervention to increase exercise in drug dependent patients represents a potentially useful yet unexplored strategy for preventing relapse. However, there are currently no established exercise interventions for use with this population. The purpose of this pilot study was to examine the feasibility of aerobic exercise as an adjunct to substance abuse treatment among drug dependent patients. Participants included 16 (31% female, 38.3 years old) drug dependent patients who participated in a 12-week, moderate-intensity aerobic exercise intervention. Participants attended a mean of 8.6 sessions (out of 12). Participants demonstrated a significant increase in percent days abstinent for both alcohol and drugs at the end of treatment, and those who attended at least 75% of the exercise sessions had significantly better substance use outcomes than those who did not. In addition, participants showed a significant increase in their cardiorespiratory fitness by the end of treatment. While preliminary, this study is one of the first to demonstrate the feasibility of incorporating aerobic exercise during drug abuse treatment. Future randomized control trials are a necessary next step to test the efficacy of a moderate-intensity aerobic exercise intervention as an adjunct to drug abuse treatment in this patient population. PMID- 20582152 TI - Healthy Living in Two Worlds: Testing a Wellness Curriculum for Urban Native Youth. AB - The Healthy Living in Two Worlds project developed a wellness curriculum for urban, Northeastern Native American youth. The curriculum sought to increase physical activity, decrease or prevent recreational tobacco use, and increase healthy eating practices. The program was delivered in a summer day camp format to 16 Native American youth ages 9-13. These youth have considerable exposure to recreational tobacco use in their households and among their peers but they express an intention to resist pressure to use recreational tobacco products. Some of these youth do not eat regular meals, particularly breakfast and lunch. Program participants appear to be physically active and their activity seems to have increased after the program. PMID- 20582154 TI - Supporting Siblings of Children with Cancer: A Need for Family-School Partnerships. AB - When a child has a chronic illness, it is readily apparent that the family and school must enter into a partnership to assure that the educational needs of the child are being met. A family-school partnership, however, may also be important to address the needs of siblings of children with chronic illness. Siblings of children with diseases such as cancer are often highly distressed and may experience decrements in academic achievement within 2 years of diagnosis. Teachers and classroom peers may be a valuable source of support to these children. This manuscript documents the mental health needs of siblings of children with cancer, describes their perceptions regarding amount of social support received and importance of social support across home and school sources, and reveals important associations between social support and more positive emotional, behavioral, and academic functioning. These findings suggest that family-school partnerships may be valuable to address the mental health needs of siblings of children with cancer. PMID- 20582153 TI - Possible applications for replicating HIV 1 vectors. AB - Since its discovery some 25 years ago, much has been learned about HIV type 1 and the molecular details of its replication cycle. This insight has been used to develop lentiviral vector systems that have advantages over conventional retroviral vector systems. For safety reasons, the lentiviral vector systems are replication incompetent and the risk of generating a replication competent virus has been minimized. Nevertheless, there may be certain applications for replication competent HIV based vector systems, and we will review our activities in this particular field. This includes the generation of a conditionally replicating HIV 1 variant as a safe live attenuated virus vaccine, the construction of mini HIV variants as cancer selective viruses for virotherapy against leukemia, and the use of a conditionally live anti HIV gene therapy vector. Although safety concerns will undoubtedly remain for the use of replication competent HIV based vector systems, some of the results in cell culture systems are very promising and warrant further testing in appropriate animal models. PMID- 20582155 TI - Validating female psychopathy subtypes: differences in personality, antisocial and violent behavior, substance abuse, trauma, and mental health. AB - Recent empirical investigations utilizing male prisoners have begun to validate clinical conceptualizations of primary and secondary psychopathy subtypes. We extended this literature by identifying similar psychopathic subtypes in female prisoners on the basis of personality structure using model-based cluster analysis. Secondary psychopaths (n = 39) were characterized by personality traits of negative emotionality and low behavioral constraint, an early onset of antisocial and criminal behavior, greater substance use and abuse, more violent behavior and institutional misconduct, and more mental health problems, including symptoms of posttraumatic stress disorder and suicide attempts. Primary psychopaths (n = 31) exhibited few distinguishing personality features but were prolific criminals especially in regards to nonviolent crime, and exhibited relatively few mental health problems despite substantial exposure to traumatic events. The results support alternative etiological pathways to antisocial and criminal behavior that are evident in personality structure as well as gender similarities and differences in the manifestation of psychopathic personalities. PMID- 20582156 TI - Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4. AB - This Letter describes a detailed SAR analysis of the mGluR4 positive allosteric modulator, PHCCC. We have now developed compounds with improved potency and efficacy; in addition, compounds are presented that show selectivity for mGluR4 versus the other mGluR subtypes. PMID- 20582157 TI - Bridging: Locating Critical Connectors in a Network. AB - This paper proposes several measures for bridging in networks derived from Granovetter's (1973) insight that links which reduce distances in a network are important structural bridges. Bridging is calculated by systematically deleting links and calculating the resultant changes in network cohesion (measured as the inverse average path length). The average change for each node's links provides an individual level measure of bridging. We also present a normalized version which controls for network size and a network level bridging index. Bridging properties are demonstrated on hypothetical networks, empirical networks, and a set of 100 randomly generated networks to show how the bridging measure correlates with existing network measures such as degree, personal network density, constraint, closeness centrality, betweenness centrality, and vitality. Bridging and the accompanying methodology provide a family of new network measures useful for studying network structure, network dynamics, and network effects on substantive behavioral phenomenon. PMID- 20582158 TI - Effects of prenatal care on maternal postpartum behaviors. AB - Most research on the effectiveness of prenatal care has focused on birth outcomes and has found small or no effects. It is possible, however, that prenatal care is "too little too late" to improve pregnancy outcomes in the aggregate, but that it increases the use of pediatric health care or improves maternal health-related parenting practices and, ultimately, child health. We use data from the Fragile Families and Child Wellbeing birth cohort study that have been augmented with hospital medical record data to estimate effects of prenatal care timing on pediatric health care utilization and health-related parenting behaviors during the first year of the child's life. We focus on maternal postpartum smoking, preventive health care visits for the child, and breastfeeding. We use a multi pronged approach to address the potential endogeneity of the timing of prenatal care. We find that first trimester prenatal care appears to decrease maternal postpartum smoking by about 5 percentage points and increase the likelihood of 4 or more well-baby visits by about 1 percentage point, and that it may also have a positive effect on breastfeeding. These findings suggest that there are benefits to standard prenatal care that are generally not considered in evaluations of prenatal care programs and interventions. PMID- 20582159 TI - A DERATING METHOD FOR THERAPEUTIC APPLICATIONS OF HIGH INTENSITY FOCUSED ULTRASOUND. AB - Current methods of determining high intensity focused ultrasound (HIFU) fields in tissue rely on extrapolation of measurements in water assuming linear wave propagation both in water and in tissue. Neglecting nonlinear propagation effects in the derating process can result in significant errors. In this work, a new method based on scaling the source amplitude is introduced to estimate focal parameters of nonlinear HIFU fields in tissue. Focal values of acoustic field parameters in absorptive tissue are obtained from a numerical solution to a KZK type equation and are compared to those simulated for propagation in water. Focal waveforms, peak pressures, and intensities are calculated over a wide range of source outputs and linear focusing gains. Our modeling indicates, that for the high gain sources which are typically used in therapeutic medical applications, the focal field parameters derated with our method agree well with numerical simulation in tissue. The feasibility of the derating method is demonstrated experimentally in excised bovine liver tissue. PMID- 20582160 TI - On the Origin of the Chemical Barrier and Tunneling in Enzymes. AB - This paper presents both a review of some recent results from our group and experimental groups, and some new theoretical results all of which are helping to form a more physically rigorous picture of the process of enzymatic catalysis. A common classical picture of enzymatic catalysis is the transition state tight binding model. Schwartz and Schramm1 have recently argued from both theoretical and experimental results that this picture is incorrect. We now investigate what the nature of barriers might be in enzymatic reactions, and what this viewpoint might imply for tunneling in a hydrogen transfer enzyme. For lactate dehydrogenase we conclude that the enzymes role in catalysis is at least partially to hunt through configuration space for those configurations that minimize chemical free energy barriers. Those configurations do not seem to be stable basins on the free energy surface, and in fact the overall free energy barrier to reaction may well largely be due to this stochastic hunt - both probabilistically and energetically. We suggest further computations to test this hypothesis. PMID- 20582162 TI - Image-based models of cardiac structure in health and disease. AB - Computational approaches to investigating the electromechanics of healthy and diseased hearts are becoming essential for the comprehensive understanding of cardiac function. In this article, we first present a brief review of existing image-based computational models of cardiac structure. We then provide a detailed explanation of a processing pipeline which we have recently developed for constructing realistic computational models of the heart from high resolution structural and diffusion tensor (DT) magnetic resonance (MR) images acquired ex vivo. The presentation of the pipeline incorporates a review of the methodologies that can be used to reconstruct models of cardiac structure. In this pipeline, the structural image is segmented to reconstruct the ventricles, normal myocardium, and infarct. A finite element mesh is generated from the segmented structural image, and fiber orientations are assigned to the elements based on DTMR data. The methods were applied to construct seven different models of healthy and diseased hearts. These models contain millions of elements, with spatial resolutions in the order of hundreds of microns, providing unprecedented detail in the representation of cardiac structure for simulation studies. PMID- 20582163 TI - Alcoholism and Strongyloides stercoralis: daily ethanol ingestion has a positive correlation with the frequency of Strongyloides larvae in the stools. AB - BACKGROUND: Significantly higher prevalence of Strongyloides stercoralis has been reported in chronic alcoholic patients. The aim of this investigation was to report the prevalence of Strongyloides larvae in stools of chronic alcoholic patients with known daily ethanol intake. METHODS: From January 2001 through December 2003 the results of fecal examinations and the daily ethanol intake were retrieved from the records of 263 chronic alcoholic and from 590 non-alcoholic male patients that sought health care at the outpatients unit of the University Hospital C A Moraes. Alcoholic patients were separated into four groups, with 150g intervals between the groups according to the daily ethanol intake. RESULTS: (a) The frequency of Strongyloides was significantly higher in alcoholic patients than in control group (overall prevalence in alcoholic 20.5% versus 4.4% in control group; p = 0.001). Even in the group with a daily intake of ethanol equal to or less than 150g the prevalence was higher than in control group, although non significant (9.5%, versus 4.4% in control group; p = 0,071); (b) the prevalence of Strongyloides in alcoholic patients rises with the increase of ethanol intake (Pearson's Correlation Coefficient = 0.956; p = 0.022), even in patients without liver cirrhosis (Pearson's Correlation Coefficient = 0.927; p = 0.037). CONCLUSION: These results confirm and reinforce the hypothesis that chronic alcoholism is associated with Strongyloides infection, which is in direct relationship with the severity of alcoholism, independently of the presence of liver cirrhosis. PMID- 20582161 TI - Polymer nanofibrous structures: Fabrication, biofunctionalization, and cell interactions. AB - Extracellular matrix fibers (ECM) such as collagen, elastin, and keratin provide biological and physical support for cell attachment, proliferation, migration, differentiation and ultimately cell fate. Therefore, ECM fibers are an important component in tissue and organ development and regeneration. Meanwhile, polymer nanofibers could play the same critical role in tissue regeneration process. Fibrous structures can be fabricated from a variety of materials and methods with diameters ranging throughout the size scale where cells can sense individual fibers (several nanometers to several microns). Polymer nanofiber scaffolds can be designed in a way that predictably modulates a variety of important cell behaviors towards a desired overall function. The nanofibrous topography itself, independent of the fiber material, has demonstrated the potential to modulate cell behaviors desirable in tissue engineering such as: unidirectional alignment; increased viability, attachment, and ECM production; guided migration; and controlled differentiation. The versatility of polymer nanofibers for functionalization with biomolecules opens the door to vast opportunities for the design of tissue engineering scaffolds with even greater control over cell incorporation and function. Despite the promise of polymer nanofibers as tissue engineering scaffolds there have been few clinically relevant successes because no single fabrication technique currently combines control over structural arrangement, material composition, and biofunctionalization, while maintaining reasonable cost and yield. Promising strategies are currently being investigated to allow for the fabrication of optimal polymer nanofiber tissue engineering scaffolds with the goal of treating damaged and degenerated tissues in a clinical setting. PMID- 20582164 TI - Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini. AB - The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies. PMID- 20582165 TI - Selected microRNAs define cell fate determination of murine central memory CD8 T cells. AB - During an immune response T cells enter memory fate determination, a program that divides them into two main populations: effector memory and central memory T cells. Since in many systems protection appears to be preferentially mediated by T cells of the central memory it is important to understand when and how fate determination takes place. To date, cell intrinsic molecular events that determine their differentiation remains unclear. MicroRNAs are a class of small, evolutionarily conserved RNA molecules that negatively regulate gene expression, causing translational repression and/or messenger RNA degradation. Here, using an in vitro system where activated CD8 T cells driven by IL-2 or IL-15 become either effector memory or central memory cells, we assessed the role of microRNAs in memory T cell fate determination. We found that fate determination to central memory T cells is under the balancing effects of a discrete number of microRNAs including miR-150, miR-155 and the let-7 family. Based on miR-150 a new target, KChIP.1 (K (+) channel interacting protein 1), was uncovered, which is specifically upregulated in developing central memory CD8 T cells. Our studies indicate that cell fate determination such as surface phenotype and self-renewal may be decided at the pre-effector stage on the basis of the balancing effects of a discrete number of microRNAs. These results may have implications for the development of T cell vaccines and T cell-based adoptive therapies. PMID- 20582166 TI - Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha) recruits bone marrow derived cells to the murine pulmonary vasculature. AB - BACKGROUND: Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We used a mouse bone marrow transplant model in which lethally irradiated mice were rescued with bone marrow transplanted from green fluorescent protein (GFP)(+) transgenic mice to determine the role of HIMF in recruiting BMD cells to the lung vasculature during PH development. Exposure to chronic hypoxia and pulmonary gene transfer of HIMF were used to induce PH. Both models resulted in markedly increased numbers of BMD cells in and around the pulmonary vasculature; in several neomuscularized small (approximately 20 microm) capillary like vessels, an entirely new medial wall was made up of these cells. We found these GFP(+) BMD cells to be positive for stem cell antigen-1 and c-kit, but negative for CD31 and CD34. Several of the GFP(+) cells that localized to the pulmonary vasculature were alpha-smooth muscle actin(+) and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs). The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3 kinase-dependent manner. CONCLUSIONS/SIGNIFICANCE: These results demonstrate HIMF dependent recruitment of BMD mesenchymal-like cells to the remodeling pulmonary vasculature. PMID- 20582167 TI - Metallomic profiling and linkage map analysis of early Parkinson's disease: a new insight to aluminum marker for the possible diagnosis. AB - BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative disorder. The diagnosis of PD is challenging and currently none of the biochemical tests have proven to help in diagnosis. Serum metallomic analysis may suggest the possibility of diagnosis of PD. METHODOLOGY/RESULTS: The metallomic analysis was targeted on 31 elements obtained from 42 healthy controls and 45 drug naive PD patients using ICP-AES and ICP-MS to determine the concentration variations of elements between PD and normal. The targeted metallomic analysis showed the significant variations in 19 elements of patients compared to healthy control (p<0.04). The partial least squares discriminant analysis (PLS-DA) showed aluminium, copper, iron, manganese and zinc are the key elements, contributes the separation of PD patients from control samples. The correlation coefficient analysis and element-element ratio confirm the imbalance of inter-elements relationship in PD patients' serum. Furthermore, elements linkage map analysis showed aluminium is a key element involved in triggering of phosphorus, which subsequently lead to imbalance of homeostatic in PD serum. The execution of neural network using elements concentrations provides 95% accuracy in detection of disease. CONCLUSIONS/SIGNIFICANCE: These results suggest that there is a disturbance in the elements homeostasis and inter-elements relationship in PD patients' serum. The analysis of serum elements helps in linking the underlying cellular processes such as oxidative stress, neuronal dysfunction and apoptosis, which are the dominating factors in PD. Also, these results increase the prospect of detection of early PD from serum through neural network algorithm. PMID- 20582169 TI - Asthma and allergic rhinitis: Linked in treatment and outcomes. PMID- 20582168 TI - Targeting mitochondrial cell death pathway to overcome drug resistance with a newly developed iron chelate. AB - BACKGROUND: Multi drug resistance (MDR) or cross-resistance to multiple classes of chemotherapeutic agents is a major obstacle to successful application of chemotherapy and a basic problem in cancer biology. The multidrug resistance gene, MDR1, and its gene product P-glycoprotein (P-gp) are an important determinant of MDR. Therefore, there is an urgent need for development of novel compounds that are not substrates of P-glycoprotein and are effective against drug-resistant cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this present study, we have synthesized a novel, redox active Fe (II) complex (chelate), iron N- (2 hydroxy acetophenone) glycinate (FeNG). The structure of the complex has been determined by spectroscopic means. To evaluate the cytotoxic effect of FeNG we used doxorubicin resistant and/or sensitive T lymphoblastic leukemia cells and show that FeNG kills both the cell types irrespective of their MDR phenotype. Moreover, FeNG induces apoptosis in doxorubicin resistance T lymphoblastic leukemia cell through mitochondrial pathway via generation reactive oxygen species (ROS). This is substantiated by the fact that the antioxidant N-acetyl cysteine (NAC) could completely block ROS generation and, subsequently, abrogated FeNG induced apoptosis. Therefore, FeNG induces the doxorubicin resistant T lymphoblastic leukemia cells to undergo apoptosis and thus overcome MDR. CONCLUSION/SIGNIFICANCE: Our study provides evidence that FeNG, a redox active metal chelate may be a promising new therapeutic agent against drug resistance cancers. PMID- 20582170 TI - New FDA safety warnings for LABAs: A call for asthma guidelines revisit for solo beta agonist. PMID- 20582171 TI - The calcified lung nodule: What does it mean? AB - The aim of this review is to present a pictorial essay emphasizing the various patterns of calcification in pulmonary nodules (PN) to aid diagnosis and to discuss the differential diagnosis and the pathogenesis where it is known. The imaging evaluation of PN is based on clinical history, size, distribution and the gross appearance of the nodule as well as feasibility of obtaining a tissue diagnosis. Imaging is instrumental in the management of PN and one should strive not only to identify small malignant tumors with high survival rates but to spare patients with benign PN from undergoing unnecessary surgery. The review emphasizes how to achieve these goals. One of the most reliable imaging features of a benign lesion is a benign pattern of calcification and periodic follow-up with computed tomography showing no growth for 2 years. Calcification in PN is generally considered as a pointer toward a possible benign disease. However, as we show here, calcification in PN as a criterion to determine benign nature is fallacious and can be misleading. The differential considerations of a calcified lesion include calcified granuloma, hamartoma, carcinoid, osteosarcoma, chondrosarcoma and lung metastases or a primary bronchogenic carcinoma among others. We describe and illustrate different patterns of calcification as seen in PN on imaging. PMID- 20582172 TI - Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients. AB - BACKGROUND: The aim of this study was to evaluate treatment outcomes in patients with thoracic actinomycosis and identify patient characteristics associated with unfavorable responses to antibiotic therapy. METHODS: A retrospective analysis was performed on 40 patients with pathologically confirmed thoracic actinomycosis. RESULTS: Initial surgical treatment was performed on 17 patients to control severe symptoms such as hemoptysis or rule out lung cancer. Sixteen (94%) patients were successfully treated, including three patients who did not receive postoperative antibiotics, and one patient died of a postoperative complication. The median duration of oral antibiotic therapy after surgery was 3 months. After the diagnosis of actinomycosis, 23 patients began antibiotic therapy. The median duration of oral antibiotic therapy was 5 months. Favorable treatment outcomes were achieved in 18 of these 23 patients (78%), while five (22%) showed unfavorable responses to antibiotic therapy. Surgery was successfully performed in these five patients. The patients with unfavorable responses to antibiotic therapy had a longer duration of symptoms prior to treatment (median, 10 months) as compared to patients with favorable responses (median, 2 months; P = 0.012). CONCLUSIONS: Medical treatment failure is possible in patients with thoracic actinomycosis, and close monitoring is necessary in those who begin antibiotic therapy. In addition, surgical resection may be a valid option for patients who do not respond to antibiotic therapy, with the consideration of the age and comorbid conditions. PMID- 20582174 TI - Acinetobacter pneumonia: Is the outcome different from the pneumonias caused by other agents. AB - BACKGROUND: The principal aim of the present study was to determine whether Acinetobacter spp. pneumonia differs from hospital-acquired pneumonias (HAPs) caused by other agents with respect to therapeutic success and survival rate. METHODS: This study includes 140 adult patients diagnosed with HAPs caused by identified etiologic agents between March 2005 and February 2006. These patients were divided into two groups according to the agent responsible for their infection (Acinetobacter spp. [n = 63] or non-Acinetobacter spp. [n = 77]). The groups were compared in terms of risk factors, therapeutic success and six-week survival rates. RESULTS: Previous antibiotic use and the risk of aspiration were independent factors responsible for the development of Acinetobacter spp. pneumonia. Hypoalbuminemia, steroid use and the use of a mechanical ventilator were determined to be mortality-associated independent risk factors for Acinetobacter spp. pneumonia. The clinical success rate at the end of therapy was 41.6% and, at the sixth week, the survival rate was 35% among patients in whom Acinetobacter spp. was the causative agent. Conversely, in the control group, these values were 43 and 32%, respectively (P > 0.05). We found that the use of the appropriate antibiotics for the treatment of Acinetobacter spp. pneumonia was an important factor in survival (P < 0.001). CONCLUSION: The outcomes of Acinetobacter spp. pneumonia do not differ from HAPs associated with non Acinetobacter spp. in terms of therapeutic success and survival rates. PMID- 20582173 TI - Sarcoidosis-associated pulmonary hypertension: Clinical features and outcomes in Arab patients. AB - BACKGROUND: Pulmonary hypertension (PH) occurs in many patients with interstitial lung disease, including sarcoidosis. We explored the frequency, clinical characteristics and outcomes of PH in Arab patients diagnosed with pulmonary sarcoidosis. METHODS: A retrospective study in three tertiary hospitals was performed on 96 patients who underwent Doppler echocardiography. Demographic and clinical characteristics, physiological studies and computed tomography (CT) results were collected, and compared between patients with and without PH. RESULTS: Twenty (20.8%) patients were found to have PH. Patients with PH were more likely to be symptomatic (cough, P = 0.008; dyspnea, P = 0.04), to have an advanced radiographic stage (P = 0.001), and to be receiving systemic therapy (P = 0.001), compared to those without PH. Physiological data including pulmonary function test parameters, arterial blood gas levels and oxygen saturation at rest and after exercise were all significantly lower in patients with PH compared to those without PH. Comparison of CT patterns between patients with and without PH showed significant differences in the frequencies of ground-glass opacity (61.5 vs. 28.8%, P = 0.032) and fibrosis (76.9 vs. 44.2%, P = 0.035). In total, four patients died during the study period, including three with evidence of PH. CONCLUSIONS: The frequency of PH in the present study was 20.8%. Clinical, physiologic and radiographic characteristics appeared to differentiate patients with PH from those without PH. The presence of PH contributed to poor outcomes in patients with pulmonary sarcoidosis. PMID- 20582175 TI - Pulmonary embolism in intensive care unit: Predictive factors, clinical manifestations and outcome. AB - OBJECTIVE: To determine predictive factors, clinical and demographics characteristics of patients with pulmonary embolism (PE) in ICU, and to identify factors associated with poor outcome in the hospital and in the ICU. METHODS: During a four-year prospective study, a medical committee of six ICU physicians prospectively examined all available data for each patient in order to classify patients according to the level of clinical suspicion of pulmonary thromboembolism. During the study periods, all patients admitted to our ICU were classified into four groups. The first group includes all patients with confirmed PE; the second group includes some patients without clinical manifestations of PE; the third group includes patients with suspected and not confirmed PE and the fourth group includes all patients with only deep vein thromboses (DVTs) without suspicion of PE. The diagnosis of PE was confirmed either by a high-probability ventilation/perfusion (V/Q) scan or by a spiral computed tomography (CT) scan showing one or more filling defects in the pulmonary artery or in its branches. The diagnosis was also confirmed by echocardiography when a thrombus in the pulmonary artery was observed. RESULTS: During the study periods, 4408 patients were admitted in our ICU. The diagnosis of PE was confirmed in 87 patients (1.9%). The mean delay of development of PE was 7.8 +/- 9.5 days. On the day of PE diagnosis, clinical examination showed that 50 patients (57.5%) were hypotensive, 63 (72.4%) have SIRS, 15 (17.2%) have clinical manifestations of DVT and 71 (81.6%) have respiratory distress requiring mechanical ventilation. In our study, intravenous unfractionated heparin was used in 81 cases (93.1%) and low molecular weight heparins were used in 4 cases (4.6%). The mean ICU stay was 20.2 +/- 25.3 days and the mean hospital stay was 25.5 +/- 25 days. The mortality rate in ICU was 47.1% and the in-hospital mortality rate was 52.9%. Multivariate analysis showed that factors associated with a poor prognosis in ICU are the use of norepinephrine and epinephrine. Furthermore, factors associated with in hospital poor outcome in multivariate analysis were a number of organ failure associated with PE >/= 3. MOREOVER, COMPARISON BETWEEN PATIENTS WITH AND WITHOUT PE SHOWED THAT PREDICTIVE FACTORS OF PE ARE: acute medical illness, the presence of meningeal hemorrhage, the presence of spine fracture, hypoxemia with PaO(2)/FiO(2) ratio <300 and the absence of pharmacological prevention of venous thromboembolism. CONCLUSION: Despite the high frequency of DVT in critically ill patients, symptomatic PE remains not frequently observed, because systematic screening is not performed. Pulmonary embolism is associated with a high ICU and in-hospital mortality rate. Predictive factors of PE are acute medical illness, the presence of meningeal hemorrhage, the presence of spine fracture, hypoxemia with PaO(2)/FiO(2) < 300 and the absence of pharmacological prevention of venous thromboembolism. PMID- 20582176 TI - Virtual and fiber-optic bronchoscopy in patients with indication for tracheobronchial evaluation. AB - OBJECTIVE: The aim of this study was to compare the results of virtual bronchoscopy (VB) images in defining tracheobronchial pathologies with those of fiber-optic bronchoscopy (FOB) in patients with clinical indication for bronchoscopy. METHODS: Twenty-two patients with bronchoscopy indication were evaluated with FOB and VB. The VB results were evaluated blindly, independent of the FOB results. RESULTS: In 19 of the 22 patients, tracheobronchial abnormalities were present on FOB, whereas 3 patients had normal findings on FOB. In 17 of 19 patients, VB demonstrated the FOB diagnosis of tracheobronchial abnormality. While FOB detected 11 endoluminal lesions, VB detected 6. While FOB detected 20 obstructive lesions, VB detected 26. In evaluating external compression, FOB detected 2 lesions and VB detected 15. CONCLUSIONS: VB is a non invasive, uncomplicated, and reproducible examination method in patients with an indication for thorax examination. Virtual bronchoscopy could find a clinically broader field of application in the future. PMID- 20582177 TI - H1N1 infection-induced thyroid storm. AB - A thyroid storm is a life-threatening exacerbation of thyrotoxicosis, and is usually characterized by hyperthermia, tachycardia, severe agitation and altered mental status. A thyroid storm may be triggered by many causes, including systemic pulmonary infections. Delay in prompt diagnosis leads to high mortality. We present the first case of H1N1 infection triggering a thyroid storm. The delay in diagnosis because of preoccupancy with the H1N1 pandemic may have contributed to the poor outcome. When assessing cases with H1N1 infection, physicians should be more vigilant in order not to miss other important diagnoses. PMID- 20582178 TI - Melioidosis and pulmonary tuberculosis co-infection in a diabetic. AB - Burkholderia pseudomallei is the causative agent of melioidosis. It is endemic in South East Asian countries and North Australia. Sporadic cases of melioidosis have been reported from several parts of South India. Melioidosis may manifest as chronic pneumonia mimicking tuberculosis and generally be seen as a single entity. We report the first case of melioidosis and pulmonary tuberculosis co infection in a diabetic patient. The causative agents were identified using standard methods and the patient recovered after completion of the recommended antibiotic therapy. Melioidosis is an emerging infectious disease in India. Though melioidosis and tuberculosis present with similar clinical picture, co infections are rare. Hence, increased awareness among clinicians and microbiologists can help in diagnosing the disease even when there is no clinical suspicion. PMID- 20582179 TI - An elderly man having large pulmonary mass and chest pain. PMID- 20582180 TI - Prevalence of asthma in school children in rural India. PMID- 20582181 TI - QuantiFERON-TB gold test versus tuberculin skin test. PMID- 20582182 TI - Influenza vaccination among healthcare workers at a tertiary care hospital in Saudi Arabia: Facing challenges. PMID- 20582183 TI - Exenatide: a new promising antidiabetic agent. AB - Exenatide is a unique agent which can effectively control blood glucose levels in type 2 diabetes mellitus without producing dangerous adverse effects. In addition, it can lower body weight which is very essential for the treatment of obese type 2 diabetes mellitus patients. Since it can delay the destruction of islet beta-cells, type 2 diabetes mellitus patients are not rapidly converted to type 1 diabetes mellitus and ultimately appearance of complications of the disease is halted or delayed. Its long-acting-release formula, which would be used once per week, simultaneously retaining all the properties of twice-daily subcutaneous administration, is undergoing clinical trial. This drug is considered as an adjunct to metformin/sulfonylureas/insulin. PMID- 20582184 TI - Monoclonal antibodies as diagnostics; an appraisal. AB - Ever since the development of Hybridoma Technology in 1975 by Kohler and Milstein, our vision for antibodies as tools for research for prevention, detection and treatment of diseases, vaccine production, antigenic characterization of pathogens and in the study of genetic regulation of immune responses and disease susceptibility has been revolutionized. The monoclonal antibodies being directed against single epitopes are homogeneous, highly specific and can be produced in unlimited quantities. In animal disease diagnosis, they are very useful for identification and antigenic characterization of pathogens. Monoclonal antibodies have tremendous applications in the field of diagnostics, therapeutics and targeted drug delivery systems, not only for infectious diseases caused by bacteria, viruses and protozoa but also for cancer, metabolic and hormonal disorders. They are also used in the diagnosis of lymphoid and myeloid malignancies, tissue typing, enzyme linked immunosorbent assay, radio immunoassay, serotyping of microorganisms, immunological intervention with passive antibody, antiidiotype inhibition, or magic bullet therapy with cytotoxic agents coupled with anti mouse specific antibody. Recombinant deoxyribonucleic acid technology through genetic engineering has successfully led to the possibility of reconstruction of monoclonal antibodies viz. chimeric antibodies, humanized antibodies and complementarily determining region grafted antibodies and their enormous therapeutic use. PMID- 20582185 TI - Development and Evaluation of pH-Dependent Micro Beads for Colon Targeting. AB - The purpose of this research was to develop and evaluate multiparticulates of alginate and chitosan hydrogel beads exploiting pH sensitive property for colon targeted delivery of theophylline. Alginate and chitosan beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S100. All formulations were evaluated for particle size, encapsulation efficiency, swellability and in vitro drug release.In vitro dissolution studies performed following pH progression method demonstrated that the drug release from coated beads depends on coat weights applied and pH of dissolution media. Mechanism of drug release was found to be swelling and erosion-dependent. The studies showed that formulated alginate and chitosan beads can be used effectively for the delivery of drug to colon and a coat weight of 20% weight gain was sufficient to impart an excellent gastro resistant property to the beads for effective release of drug at higher pH values. PMID- 20582186 TI - Synthesis, characterization and histopathological study of a lead-based Indian traditional drug: naga bhasma. AB - The aim of the present study is to prepare and characterize Naga bhasma on structural and elemental basis to address the role of the raw materials used during the preparation, compound form of the lead bhasma, nature (crystalline/amorphous) and crystallite/particle size of the drug. The study also covers the toxicological effect of the drug on albino rats. It was found that drug contains lead in nano-crystalline (~60 nm) lead sulfide form (Pb(2+)) associated with the organic contents and different nutrient elements coming from the herbs used during the preparation. Naga bhasma prepared was found to be totally safe in histopathology study on rats at a dose of 6 mg/100 g/day. The different characterization techniques used present a role model for the quality control and standardization of such kinds of herbo-metallic medicines. PMID- 20582187 TI - A radiometric study of factors affecting drug output of jet nebulizers. AB - Jet nebulizers show an unreasonable variation in drug output and nebulization rates that leads to clinical and regulatory problems. Current evaluation methods appear inadequate for the purpose. Our objective was to evaluate Technetium-99m radiometry to study nebulizer parameters and the factors influencing it quantitatively. Drug output, output rate and residual mass and the effect of excipient, temperature, surface tension, air-jet speed, and equipment brand and aging were studied. Though nebulization of radiolabeled drugs followed first order kinetics, the rates were significantly different; the heaviest drug (Tc-99m colloid) and Tc-99m salbutamol had the least nebulization. Nebulization rate for the first minute was invariably higher than the mean rate signifying the concentration effect of the solute. Drug residue was 35-75%. Drug output of different nebulizer chamber and air compressor brands was different to the extent of 270% and 180% respectively. 'Aging' of fluid chamber, cold drug fluid and obstruction in air-jet resulted in significant reduction in output, while addition of 2% saline as excipient did not change the output rate. Addition of ethyl alcohol resulted in a maximum of 260% enhancement (with Tc-99m salbutamol), while further reduction in surface tension was counterproductive irrespective of the drug used. We conclude that radiometry can provide valuable parametric information on the performance of different jet nebulizers. PMID- 20582188 TI - Comparative phytochemical investigation of the sources of ayurvedic drug patha: a chromatographic fingerprinting analysis. AB - Standardization of herbal drugs based on their chemical and biological activity profile is an important prerequisite for acquiring the herbal market. The main problem encountered in standardization of Ayurvedic drugs is proper identification of the source plant. The present study was aimed to establish identification characters, quality control parameters, chemical and biological parameters for roots of three plants Cissampelos pareira, Cyclea peltata and Stephania japonica (Fam. Menispermaceae) which are being used as source of Patha, in the market. All the three plant were subjected for evaluation of quality control parameters as per WHO guidelines and root extracts and total alkaloidal fractions were subjected for HPTLC and HPLC fingerprinting analysis using a marker compound Bebeerine isolated from roots of Cissampelos pareira. The parameters studied clearly indicated the significant differences among the three plant materials. The roots of Cissampelos pareira can be distinguished from other two plants by presence of high concentration of alkaloids especially the presence of high concentration of pharmacologically active alkaloid bebeerine, which was found to be present in very low concentration in Stephania japonica and absent in roots of Cyclea peltata. The roots of Cyclea peltata were found to contain high concentration of saponins and comparatively in low concentration in Cissampelos pareira where as it was found to be absent in roots of Stephania japonica. PMID- 20582189 TI - Degradation kinetics of benzyl nicotinate in aqueous solution. AB - The degradation of benzyl nicotinate in aqueous solution over a pH range of 2.0 10.0 at 50+/-0.2 degrees was studied. The degradation was determined by high performance liquid chromatography. The degradation was observed to follow apparent first-order rate kinetics and the rate constant for the decomposition at 25 degrees was estimated by extrapolation. The reaction was shown to be hydroxide ion catalyzed and the Arrhenius plots showed the temperature dependence of benzyl nicotinate degradation. A significant increase in the stability of benzyl nicotinate was observed when glycerol or polyethylene glycol 400 was incorporated into the aqueous solution. PMID- 20582190 TI - A supercritical fluid chromatography/tandem mass spectrometry method for the simultaneous quantification of metformin and gliclazide in human plasma. AB - Present study reports the development and validation of a simultaneous estimation of metformin and gliclazide in human plasma using supercritical fluid chromatography followed by tandem mass spectrometry. Acetonitrile:water (80:20) mixture was used as a mobile phase along with liquid CO(2) in supercritical fluid chromatography and phenformin as an internal standard. The modified plasma samples were analyzed by electro-spray ionization method in selective reaction monitoring mode in tandem mass spectrometry. Supercritical fluid chromatographic separation was performed using nucleosil C(18) containing column as a stationary phase. The separated products were identified by characteristic peaks and specific fragments peaks in tandem mass spectrometry as m/z 130 to 86 for metformin, m/z 324 to 110 for gliclazide and m/z 206 to 105 for phenformin. The present method was found linear in the concentration ranges of 6.0-3550 ng/ml and 7.5-7500 ng/ml for metformin and gliclazide, respectively. Pharmacokinetic study was performed after an oral administration of dispersible tablets containing 500 mg of metformin and 80 mg of gliclazide using same techniques. PMID- 20582191 TI - Multiparticulate system for colon targeted delivery of ondansetron. AB - Targeted delivery of drugs to colon has the potential for local treatment of a variety of colonic diseases. The main objective of the study was to develop a multiparticulate system containing chitosan microspheres for the colon targeted delivery of ondansetron for the treatment of irritable bowel syndrome. This work combines pH-dependent solubility of eudragit S-100 polymers and microbial degradability of chitosan polymers. Chitosan microspheres containing ondansetron were prepared by emulsion cross linking method. The effect of process variables like chitosan concentration, drug-polymer ratio, emulsifier concentration and stirring speed were studied on particle size and entrapment efficiency of chitosan microspheres. In vitro drug release studies in simulated gastro intestinal fluids showed a burst drug release pattern in the initial hour necessitating microencapsulation around the chitosan microspheres. The optimized formulation was then subjected to microencapsulation with eudragit S-100 by solvent evaporation technique. The effect of different coat/core ratio on particle size, drug entrapment efficiency and in vitro drug release were studied. Formulation which contain 1:10 core/coat ratio released lesser amount of drug in the upper gastro intestinal conditions and so selected as best formulation and then subjected to in vitro drug release studies in presence of rat ceacal contents to assess biodegradability of chitosan microspheres in colon. In order to study the drug release mechanism in vitro drug release data was fitted into various kinetic models. Analysis of regression values suggested that the possible drug release mechanism was Peppas model. PMID- 20582192 TI - Topical formulations of serratiopeptidase: development and pharmacodynamic evaluation. AB - Serratiopeptidase, an enzyme derived from Serratia marcescences strain E-15 (ATCC 21074), present in the gut wall of the silk worm possesses anti-inflammatory properties, and can prove to be a suitable alternative to commonly used non steroidal antiinflammatory agents. Being sensitive to gastric degradation, serratiopeptidase is conventionally given orally in the form of enteric coated tablet formulations. Topical formulations of serratiopeptidase would be useful to treat local inflammations and may prove to be more effective compared to non steroidal antiinflammatory agents. The present study investigates the feasibility of developing topical preparations of serratiopeptidase in the form of ointments and gels. Excipient compatibility of serratiopeptidase with various excipients and polymers, formulation development, characterization and stability studies have been carried out. Stable formulation was evaluated for anti-inflammatory activity by oxazolone induced ear edema method in mice and allergenic potential by passive cutaneous anaphylaxis. PMID- 20582193 TI - Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method. AB - The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres were prepared by using water-in-oil-in-oil (W/O(1)/O(2)) double emulsion solvent diffusion method, using different ratios of ethylcellulose to tolmetin sodium. Span 80 was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties, drug content, loading efficiency, production yield, and particle size. Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to characterize microparticles. The in vitro release studies were performed in pH 1.2 and 7.4. The prepared microspheres were spherical in shape. The drug-loaded microspheres showed near to the theoretical of entrapment and release was extended up to 24. The X-ray diffractogram and differential scanning thermographs showed amorphous state of the drug in the microspheres. It was shown that the drug: polymer ratio, stirring rate, volume of dispersing medium and surfactant influenced the drug loading, particle size and drug release behavior of the formed microparticles. The results showed that, generally, an increase in the ratio of drug: polymer (0.5:1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The in vitro release profile could be modified by changing various processing and formulation parameters to give a controlled release of drug from the microparticules. The release of tolmetin was influenced by the drug to polymer ratio and particle size and was found to be diffusion and erosion controlled. The best-fit release kinetic was achieved with Peppas model. PMID- 20582194 TI - Formulation and evaluation of rizatriptan benzoate mouth disintegrating tablets. AB - The present investigation deals with development of mouth disintegrating tablets of rizatriptan benzoate to produce the intended benefits. Mouth disintegrating tablets of rizatriptan benzoate were prepared using superdisintegrants crospovidone, carboxymethylcellulose calcium, Indion 414 and Indion 234 using the direct compression method. The tablets prepared were evaluated for thickness, uniformity of weight, content uniformity, hardness, friability, wetting time, in vitro and in vivo disintegration time, mouth feel, in vitro drug release and assay by high performance liquid chromatography. The tablets disintegrated in vitro and in vivo within 4 to 7 s and 6 to 19 s, respectively. Almost 90% of drug was released from all formulations within 20 min. The drug release from the formulations followed first order kinetics. Stability studies of the tablets at 40+/-2 degrees /75%+/-5% RH for 1 mo showed non significant drug loss. The formulation containing combination of crospovidone and Indion 234 was found to give the best results. Apart from fulfilling all official and other specifications, the tablets exhibited higher rate of release. PMID- 20582195 TI - Quality control standards for the roots of three plumbago species. AB - Physicochemical parameters of roots of three Plumbago species, Plumbago capensis, P. rosea and P. zeylanica belonging to Plumbaginaceae were analyzed. Microbial contamination, aflatoxins, pesticide residue and heavy metal content were also determined. Attempt has also been made to estimate the biologically active chemical plumbagin present in them and the data compared. The study ensures that the quality control parameters do help in the proper standardization of the crude drugs in drug development process for global acceptance. PMID- 20582196 TI - Characterization of indomethacin release from polyethylene glycol tablet fabricated with mold technique. AB - The purpose of this study was to use polyethylene glycol as a carrier to improve the solubility of an aqueous insoluble drug by melting and molding method. The release of dissolved drug was designed to be subsequently sustained with an addition of xanthan gum. The release of indomethacin from the developed system into phosphate buffer pH 6.2 was conducted using the dissolution apparatus. This carrier system could effectively enhance the solubility of indomethacin and an addition of xanthan gum could sustain the drug release. Eudragit L100 film coating could protect the carrier not to be disturbed with HCl buffer pH 1.2 and could dissolve in phosphate buffer pH 6.2, therefore, the drug release from coated tablet was initially very low but subsequently gradually released and prolonged in phosphate buffer pH 6.2. Differential scanning calorimetry study indicated the amorphous state of drug in polyethylene glycol carrier. Scanning electron microscopy photomicrograph indicated the drug diffusion outward through the porous network of matrix tablets into the dissolution fluid and curve fitting signified that the drug release kinetic was Fickian diffusion. PMID- 20582197 TI - Formulation and characterization of rifampicin microcapsules. AB - Rifampicin biodegradable microcapsules were prepared by feasible emulsification ionic gelation method for a novel controlled release product. Sodium alginate and Carbopol 974P were used as coating polymers in different ratios 1:1, 1:2, 1:3 and 1:4 to obtain elegant microcapsules. The formulations were characterized for encapsulation efficiency, drug loading, sieve analysis, scanning electron microscopy and in vitro release studies. The microcapsules were discrete, large, almost spherical and free flowing with encapsulation efficiency in the range of 75% to 89%, drug loading 75% to 86% and size 440 mum to 500 mum. Rifampicin release from these microcapsules was slow and extended over longer periods of time depending on the polymer coat. Drug release was diffusion controlled and followed first order kinetics. The formulation MC1 with a coating ratio of 1:1 (Sodium alginate: Carbopol 974P) was found to be suitable for oral controlled release. PMID- 20582198 TI - Antioxidant activity in the extracts of two edible aroids. AB - Two neglected species of Araceae, Alocasia macrorhiza (Linn.) G. Don and Alocasia fornicata (Roxb.) Schott are important as food and ethno medicine in Asia and Africa. Their bioefficacy is documented in the Ayurveda. The solvent extracts of different edible parts of these two species like rhizomes, leaves, roots and stolons were screened for in vitro antioxidant properties using standard procedures. The successive extracts in hexane, benzene, toluene, chloroform, diethyl ether, ethyl acetate and water fraction exhibited IC(50) values in the following order, roots>rhizome>leaves for Alocasia macrorhiza and leaves>stolon for Alocasia fornicate, respectively in 2,2-diphenyl-1-picryl hydrazyl antioxidant inhibition assay. Maximum antioxidant activity was observed in diethyl ether extracts for both species. The IC(50) values were comparable with those of quercetine and ascorbic acid as standards. These results suggest that the two aroid species have antioxidant activity in their edible parts and should be extracted using diethyl ether solvent. PMID- 20582199 TI - RP-HPLC Method for the Determination of Losartan Potassium and Ramipril in Combined Dosage Form. AB - A simple, specific and accurate reverse phase liquid chromatographic method was developed for the simultaneous determination of losartan potassium and ramipril in table dosage forms. A hypersil ODS C18, 4.6x250 mm, 5 mum column in isocratic mode, with mobile phase acetonitrile:methanol:10 mM tetra butyl ammonium hydrogen sulphate in water in the ratio of 30:30:40% v/v/v was used. The flow rate was 1.0 ml/min and effluent was monitored at 210 nm. The retention times of losartan potassium and ramipril were 4.7 and 3.3 min, respectively. The linearity range for losartan potassium and ramipril were in the range of 0.04-100 mug/ml and 0.2 300 mug/ml, respectively. The proposed method was also validated and successfully applied to the estimation of losartan potassium and ramipril in combined tablet formulations. PMID- 20582200 TI - Spectrophotometric estimation of olmesartan medoxomil and hydrochlorothiazide in tablet. AB - A simultaneous determination of olmesartan medoxomil and hydrochlorothiazide by absorption ratio spectrophotometric method has been developed in combined tablet dosage form. The method is based on measurements of absorbance at isoabsoptive point. The Beer's law obeys in the range of 10-30 mug/ml for both olmesartan medoxomil and hydrochlorothiazide respectively. The proposed method was validated by performing recovery study and statistically. PMID- 20582201 TI - RP-HPLC Method for the Estimation of Dutasteride in Tablet Dosage Form. AB - A simple, sensitive and precise RP-HPLC method was developed for the determination of dutasteride in tablet dosage form. The RP-HPLC separation was achieved on phenomenex C(18) column (250 mm, id 4.6 mm, 5 mum) using mobile phase methanol:water (90:10 v/v) at a flow rate of 1 ml/min at an ambient temperature. Quantification was achieved with photodiode array detection at 235 nm over the concentration range 1-12 mug/ml. The method was validated statistically and was applied successfully for the determination of dutasteride in tablets. PMID- 20582202 TI - Activity of Superoxide Dismutase and Catalase in Fenugreek (Trigonella foenum graecum) in Response to Carbendazim. AB - Fenugreek (Trigonella foenum-graecum) is an annual herb, used as a spice and traditionally as medicine. Fenugreek finds its uses in treating hyperglycemia, hyperlipidemia and disorders of gastro-intestinal and cardiovascular systems. Fenugreek cultivation in India is affected by fungal diseases like root-rot and damping-off and fungicides like carbendazim are used to overcome these infections. Fungicides play both positive and negative role in plants; fungicides protect plants from diseases and also exert oxidative stress simultaneously. This report is on the response of antioxidants, superoxide dismutase and catalase in fenugreek seeds and plants treated to different concentrations of carbendazim. PMID- 20582203 TI - A new stability indicating HPLC method for related substances in zolmitriptan. AB - A sensitive, precise, specific, linear and stability indicating isocratic HPLC method was developed for the analysis of related substances in zolmitriptan. The potential known related substances are (S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one (impurity I) and (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one (impurity II). The method can be used for the detection and quantification of known and unknown impurities and degradants in the drug substance zolmitriptan during routine analysis and also for stability studies in view of its capability to separate degradation products. PMID- 20582204 TI - Evaluation of Wound Healing Potential of Bauhinia purpurea Leaf Extracts in Rats. AB - The present study was carried out to evaluate the effect of methanol and chloroform extracts of Bauhinia purpurea on experimentally induced excision, incision, burn and dead space wound models in Sprague Dawley rats. Formulations of methanol and chloroform extracts of Bauhinia purpurea were prepared in carbopol and simple ointment base at concentrations of 2.5% and 5% and applied to the wounds. In the excision and burn wound models, animals treated with high doses of methanol and chloroform showed significant reduction in time taken for epithelization and wound contraction (50%) compared to control. A significant increase in breaking strength was found in incision wound model with methanol and chloroform extracts compared to their respective bases. In the dead space wound model, methanol and chloroform extract treatment (100 and 500 mg/kg) orally produced a significant increase in the breaking strength, dry tissue weight and hydroxyproline content of the granulation tissue when compared to control. Among the extracts, methanol extract exhibited more activity followed by the chloroform extract. In conclusion, the present study indicated that Bauhinia purpurea leaves exhibited wound healing activity. PMID- 20582205 TI - Effect of Flow Aids on Mucoadhesive Properties of Polymeric Discs of Polyoxyethylene and Carbopol 971P. AB - The aim of present study is to investigate the effect of flow aids on the observed in vitro mucoadhesion of two representative polymers; polyoxyethylene and Carbopol((R)) 971P. More recently it has been shown that the addition of small amounts of certain excipients to a mucoadhesive formulation can lead to a substantial decrease in observed mucoadhesion in an in vitro test system, which suggests that formulation of these systems could be crucial in developing successful dosage forms. A series of experiments has been carried out which indicates that the presence of flow aids at high concentrations present in tablets can affect the observed ex-vivo mucoadhesive bond. Magnesium stearate (5%) exerts its negative effect on the mucoadhesion of Carbopol((R)) 971P and polyoxyethylene combination by hindering the hydration of the polymer. Adhesion time of formulation containing 5% magnesium stearate was found 4.7+/-0.34 h and percent hydration of same formulation was 70.12%.Talc and colloidal silicon dioxide (Aerosil), which do not possess the same hydrophobic properties or have available divalent cations were found to be viable alternatives to magnesium stearate. PMID- 20582206 TI - Formulation design of fast disintegrating tablets using disintegrant blends. AB - In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method, crospovidone (up to 3% w/w) and croscarmellose sodium (up to 5% w/w) in combination were used as superdisintegrants. Since disintegrants complement each other, accelerating the disintegration process when used together. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 12 s), one promising formulation was tested for in vitro drug release pattern in phosphate buffer pH 6.8 and short-term stability (at 40 degrees /70% RH for 3 mo), drug-excipient interaction (IR spectroscopy) were studied. Among the formulations tested, formulation DCPC(4) containing 5% w/w of croscarmellose sodium and 3% w/w of crospovidone as superdisintegrant emerged as the overall best (t(50%) 7.0 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulation indicated that there were no significant changes in drug content and in vitro dispersion time (p<0.05). PMID- 20582207 TI - Simultaneous spectrophotometric determination of drotaverine hydrochloride and paracetamol in tablet. AB - Two simple, accurate and reproducible spectrophotometric methods; Q analysis and first order derivative method have been described for the simultaneous estimation of drotaverine hydrochloride and paracetamol in combined tablet dosage form. Absorption maxima of drotaverine hydrochloride and paracetamol in distilled water were found to be 303.5 nm and 243.5 nm respectively. Beer's law was obeyed in the concentration range 5-50 mug/ml for drotaverine and 5-60 mug/ml for paracetamol. In Q analysis method, two wavelengths were selected at isobestic point (277 nm) and lambda(max) of paracetamol (243.5 nm). In first order derivative method, zero crossing point for drotaverine hydrochloride and paracetamol were selected at 303.5 nm and 243.5 nm, respectively. The results of two methods were validated statistically and recovery studies were found to be satisfactory. PMID- 20582208 TI - Spectrophotometric and HPLC methods for simultaneous estimation of amlodipine besilate, losartan potassium and hydrochlorothiazide in tablets. AB - Two UV-spectrophotometric and one reverse phase high performance liquid chromatography methods have been developed for the simultaneous estimation of amlodipine besilate, losartan potassium and hydrochlorothiazide in tablet dosage form. The first UV spectrophotometric method was a determination using the simultaneous equation method at 236.5, 254 and 271 nm over the concentration range 5-25, 10-50 and 5-25 mug/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. The second UV method was a determination using the area under curve method at 231.5-241.5, 249-259 and 266-276 nm over the concentration range of 5-25, 5-25 and 10-50 mug/ml for amlodipine besilate, hydrochlorothiazide and losartan potassium, respectively. In reverse phase high performance liquid chromatography analysis is carried out using 0.025 M phosphate buffer (pH 3.7):acetonitrile (57:43 v/v) as the mobile phase and Kromasil C18 (4.6 mm i.dx250 mm) column as stationery phase with detection wavelength of 232 nm linearity was obtained in the concentration range of 2-14, 20-140 and 5-40 mug/ml for amlodipine besilate, losartan potassium and hydrochlorothiazide, respectively. Both UV-spectrophotometric and reverse phase high performance liquid chromatography methods were statistically validated and can be used for analysis of combined dose tablet formulation containing amlodipine besilate, losartan potassium and hydrochlorothiazide. PMID- 20582209 TI - Antioxidant activities of some cameroonian plants extracts used in the treatment of intestinal and infectious diseases. AB - Antioxidant activity test using two different methods namely 2,2-diphenyl-1 picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothialozinesulfonate) diammonium salt free radical scavenging test has been carried out on three Cameroonian plant extracts used in the treatment of intestinal and infectious diseases: Pittosporum mannii Hook f. (Pittosporaceae), Vepris heterophylla R. Letouzey (Rutaceae) and Ricinodendron heudelotii (Baill) Pierre ex Pax (Euphorbiaceae). Results of this study in the 2,2-diphenyl-1-picrylhydrazyl scavenging test show that the ethyl acetate extract of P. mannii and the methanol extract of V. heterophylla exhibit high free radical scavenging activities with IC(50) values of 177.74 and 204.69 mug/ml, respectively while the methanol/dichloromethane (1+1) extract of R. heudelotii showed weak free radical scavenging activities as compared to Trolox (939.19 mug/ml) used as standard. In the same manner, 2,2'-azinobis(3 ethylbenzothialozinesulfonate) diammonium salt radical scavenging test of these extracts was in accordance of the result of 2,2-diphenyl-1-picrylhydrazyl test. The antioxidant properties of these extracts probably explain partly, the use of these plants in traditional medicine for the treatment of infectious diseases and inflammations. PMID- 20582210 TI - Antioxidant and Antimicrobial Activity of Alpinia officinarum. AB - Alpinia officinarum is a rhizome belonging to the family zingeberaeceae. Hydro alcoholic extract by hot and cold maceration and methanol extract by percolation process Qualitative phytochemical analysis of extract of Alpinia officinarum rhizome showed a majority of the compound including tannins, alkaloids, flavonoids and saponins. Hydroalcoholic extract prepared by hot maceration process was found to contain more phenol and flavonol and it was measured as 50.1 mg/g and 54.02 mg/g, respectively. All the three extracts showed moderate to potent antimicrobial activity against the Bacillus cereus, Staphylococcus aureas, Pseudomonas auroginosa, Escherichia coli. None of the extracts showed antifungal activity against Aspergillus niger and Candida albicans. All the three extracts showed a concentration dependent radical scavenging activity by inhibiting diphenylpicrylhydrazyl free radical at the same time hydroalcoholic extract prepared by hot maceration process showed better reducing and total antioxidant activity. PMID- 20582211 TI - Journal of conservative dentistry is now PUBMED indexed. PMID- 20582212 TI - A new dimension to conservative dentistry: Air abrasion. AB - Air abrasion dentistry has evolved over a period of time from a new concept of an alternative means of cavity preparation to an essential means of providing a truly conservative preparation for preservation of a maximal sound tooth structure. The development of bonded restorations in combination with air abrasion dentistry provides a truly minimal intervention dentistry. This article reviews the development of air abrasion, its clinical uses, and the essential accessories required for its use. PMID- 20582213 TI - Effect of different placement techniques on marginal microleakage of deep class II cavities restored with two composite resin formulations. AB - AIM: The study aims to evaluate and compare marginal microleakage in deep class II cavities restored with various techniques using different composites. MATERIALS AND METHODS: Sixty freshly extracted teeth were divided into six groups of 10 teeth each. Standardized class II cavities were made and were restored using composites of different consistencies with different placement techniques. Group 1 with Microhybrid composite, Group 2 with Packable composite, Group 3 Microhybrid composite with a flowable composite liner, Group 4 Packable composite with a flowable composite liner, Group 5 Microhybrid composite with precured composite insert in second increment and Group 6 Packable composite with precured insert in second increment. Specimens then were stored in distilled water, thermocycled and immersed in 50% silver nitrate solution. These specimens were sectioned and evaluated for microleakage at the occlusal and cervical walls separately using stereomicroscope. RESULTS: The results demonstrated that in the occlusal wall, packable composite, showed significantly more marginal microleakage than the other groups. In the cervical wall, teeth restored with a flowable composite liner showed less marginal microleakage when compared to all other groups. CONCLUSION: Based on the results of this study, the use of flowable composite as the first increment is recommended in deep class II cavities. PMID- 20582214 TI - CT evaluation of canal preparation using rotary and hand NI-TI instruments: An in vitro study. AB - BACKGROUND: Controlled, uniformly tapered radicular preparation is a great challenge in endodontics. Improper preparation can lead to procedural errors like transportation of foramen, uneven dentine thickness, stripping of root canal, formation of ledge, zip, and elbow in curved canals. These procedural errors and their sequel can adversely affect the prognosis of treatment. AIM/OBJECTIVES: The present in vitro study aims to evaluate canal preparation based on the following factors: canal transportation, remaining dentine thickness and comparing centering ability between hand Ni-Ti K files and ProTaper rotary Ni-Ti instruments using computed tomography (CT). MATERIALS AND METHODS: For evaluation, 30 mesiobuccal roots of maxillary molars were selected. Of these, 15 roots were distributed into two groups where Group 1 included hand instrumentation with Ni-Ti K-files; and Group 2 comprised ProTaper NiTi rotary system. Pre instrumentation and post instrumentation three-dimensional CT images were obtained from root cross-sections that were 1 mm thick from apex to the canal orifice; scanned images were then superimposed and compared. RESULT: It was observed that the manual technique using hand Ni-Ti K-file produced lesser canal transportation and maintained greater dentine thickness than the rotary ProTaper technique at middle and coronal third and this difference was statistically significant. No significant difference was seen with regard to canal transportation and remaining root dentine at apical levels. With regard to centering ratio, no significant difference was seen between both the groups at all levels. CONCLUSION: ProTaper should be used judiciously, especially in curved canals, as it causes higher canal transportation and thinning of root dentine at middle and coronal levels. None of the groups showed optimal centering ability. PMID- 20582215 TI - Post cementation sensitivity evaluation of glass Ionomer, zinc phosphate and resin modified glass Ionomer luting cements under class II inlays: An in vivo comparative study. AB - OBJECTIVE: This study aims to compare the patient-perceived post-cementation sensitivity of class II metal restorations preoperatively, immediately after cementation, one week after cementation and one month after cementation with (1) Glass Ionomer luting cement (2) Zinc Phosphate cement and (3) Resin-modified Glass Ionomer luting cement. MATERIALS AND METHODS: A total of 60 patients, irrespective of sex, in the age group of 15-50 years were selected and the teeth were randomly divided into three groups of 20 each. Twenty inlay cast restorations were cemented with three different luting cements. The criteria adapted to measure tooth sensitivity in the present study were objective examination for sensitivity. (1) Cold water test (2) Compressed air test and (3) Biting pressure test. RESULTS: The patients with restorations cemented with Resin modified Glass ionomer demonstrated the least postoperative sensitivity when compared with Glass Ionomer and zinc phosphate cement at all different intervals of time evaluated by different tests. CONCLUSION: The patients with restorations cemented with resin-modified Glass ionomer demonstrated the least postoperative sensitivity. PMID- 20582216 TI - A comparative study of intra canal stress pattern in endodontically treated teeth with average sized canal diameter and reinforced wide canals with three different post systems using finite element analysis. AB - STUDY METHODOLOGY: THIS IS A COMPARATIVE STUDY OF INTRA CANAL STRESS PATTERNS IN ENDODONTICALLY TREATED MAXILLARY CENTRAL INCISOR WITH: average sized canal diameter and wide canals reinforced with three different post systems - cast post and core, carbon fiber post, stainless steel post; restored with ceramic crown using finite element analysis (FEA). All the models were subjected to a force of 100N applied at 450 to the long axis of the tooth at the middle third of the palatal surface of the restored ceramic crown. RESULTS: The FEA revealed that all the post systems showed maximum stress in the coronal and middle third of the root. Maximum stress was seen on the inner dentinal wall in case of stainless steel post followed by cast gold and carbon fiber post, both in the models without reinforcement as well as in the reinforced models. PMID- 20582217 TI - The effect of one-step and multi-step polishing systems on surface texture of two different resin composites. AB - OBJECTIVE: The purpose of this in-vitro study was to evaluate the surface roughness of two direct resin composites polished with one-step and multi-step polishing systems. MATERIALS AND METHODS: The resin composites examined in this study include minifill-hybrid composite Esthet-X (DENTSPLY/Caulk, Milford, DE, USA) and packable composite Solitaire II (Heraeus Kulzer, Inc., Southbend). A total of 42 discs (10 x 2 mm), 21 specimens of each restorative material were fabricated. Seven specimens per composite group received no polishing treatment and served as control. For each composite group, the specimens were randomly divided into two polishing systems: One-step PoGo (Dentsply/Caulk, Milford, DE, USA) and multi-step Super Snap (Shofu, Inc. Kyoto, Japan). Polishing systems were applied according to the manufacturer's instructions after being ground wet with 1200 grit silicon carbide paper. The surface roughness values were determined using a profilometer. RESULTS: Data was subjected to student's t test at a significance level of 0.05. The smoothest surfaces were achieved under Mylar strips in both the composite groups. Mean Ra values ranged from 0.09 to 0.3 mum for Esthet-X group and from 0.18 to 0.3 mum for Solitaire II with different polishing systems. The ranking of the order of surface roughness on the basis of the type of composite was as follows: Esthet-X < Solitaire II for PoGo system and Esthet-X = Solitaire II for Super Snap; and the ranking for the polishing system was: PoGo < Super Snap (P > heart > brain > epididymis > kidney > liver > lung > spleen > muscle. Real-time PCR and immunohistochemistry results revealed similar expression differences in different age testes, with high expression levels during adolescence. Immunofluorescence results suggested that PHGPx mainly expressed in Leydig cells and spermatids in mature goat testes. PMID- 20582225 TI - Generation of Fgfr3 conditional knockout mice. AB - Fibroblast growth factor receptor 3 (FGFR3), highly conserved in both humans and murine, is one of key tyrosine kinase receptors for FGF. FGFR3 is expressed in different tissues, including cartilage, brain, kidney, and intestine at different development stages. Conventional knockout of Fgfr3 alleles leads to short life span, and overgrowth of bone. In clinic, human FGFR3 mutations are responsible for three different types of chondrodysplasia syndromes including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). For better understanding of the roles of FGFR3 in different tissues at different stages of development and in pathological conditions, we generated Fgfr3 conditional knockout mice in which loxp sites flank exons 9-10 in the Fgfr3 allele. We also demonstrated that Cre-mediated recombination using Col2a1-Cre, a Cre line expressed in chondrocyte during bone development, results in specific deletion of the gene in tissues containing cartilage. This animal model will be useful to study distinct roles of FGFR3 in different tissues at different ages. PMID- 20582227 TI - Spatiotemporal drivers of dissolved organic matter in high alpine lakes: Role of Saharan dust inputs and bacterial activity. AB - The effects of many environmental stressors such as UV radiation are mediated by dissolved organic matter (DOM) properties. Therefore, determining the factors shaping spatial and temporal patterns is particularly essential in the most susceptible, low dissolved organic carbon (DOC) lakes. We analyzed spatiotemporal variations in dissolved organic carbon concentration and dissolved organic matter optical properties (absorption and fluorescence) in 11 transparent lakes located above tree line in the Sierra Nevada Mountains (Spain), and we assessed potential external (evaporation and atmospheric deposition) and internal (bacterial abundance, bacterial production, chlorophyll a, and catchment vegetation) drivers of DOM patterns. At spatial and temporal scales, bacteria were related to chromophoric DOM (CDOM). At the temporal scale, water soluble organic carbon (WSOC) in dust deposition and evaporation were found to have a significant influence on DOC and CDOM in two Sierra Nevada lakes studied during the ice-free periods of 2000-2002. DOC concentrations and absorption coefficients at 320 nm were strongly correlated over the spatial scale (n = 11, R(2) = 0.86; p < 0.01), but inconsistently correlated over time, indicating seasonal and interannual variability in external factors and a differential response of DOC concentration and CDOM to these factors. At the continental scale, higher mean DOC concentrations and more CDOM in lakes of the Sierra Nevada than in lakes of the Pyrenees and Alps may be due to a combination of more extreme evaporation, and greater atmospheric dust deposition. PMID- 20582226 TI - Water buffalo genome science comes of age. AB - The water buffalo is vital to the lives of small farmers and to the economy of many countries worldwide. Not only are they draught animals, but they are also a source of meat, horns, skin and particularly the rich and precious milk that may be converted to creams, butter, yogurt and many cheeses. Genome analysis of water buffalo has advanced significantly in recent years. This review focuses on currently available genome resources in water buffalo in terms of cytogenetic characterization, whole genome mapping and next generation sequencing. No doubt, these resources indicate that genome science comes of age in the species and will provide knowledge and technologies to help optimize production potential, reproduction efficiency, product quality, nutritional value and resistance to diseases. As water buffalo and domestic cattle, both members of the Bovidae family, are closely related, the vast amount of cattle genetic/genomic resources might serve as shortcuts for the buffalo community to further advance genome science and biotechnologies in the species. PMID- 20582228 TI - Multi-Channel Transfer Function with Dimensionality Reduction. AB - The design of transfer functions for volume rendering is a difficult task. This is particularly true for multi-channel data sets, where multiple data values exist for each voxel. In this paper, we propose a new method for transfer function design. Our new method provides a framework to combine multiple approaches and pushes the boundary of gradient-based transfer functions to multiple channels, while still keeping the dimensionality of transfer functions to a manageable level, i.e., a maximum of three dimensions, which can be displayed visually in a straightforward way. Our approach utilizes channel intensity, gradient, curvature and texture properties of each voxel. The high dimensional data of the domain is reduced by applying recently developed nonlinear dimensionality reduction algorithms. In this paper, we used Isomap as well as a traditional algorithm, Principle Component Analysis (PCA). Our results show that these dimensionality reduction algorithms significantly improve the transfer function design process without compromising visualization accuracy. In this publication we report on the impact of the dimensionality reduction algorithms on transfer function design for confocal microscopy data. PMID- 20582229 TI - Unique Patterns of Substance Misuse associated with PTSD, Depression, and Social Phobia. AB - OBJECTIVES: This study investigated the relations between post-trauma psychopathology and substance abuse in a sample of trauma-exposed college students (n = 136) assigned to four groups based on primary diagnosis: posttraumatic stress disorder, depression, social phobia, or well-adjusted (participants who had low levels of distress). Groups were compared on a series of dimensions of substance use/abuse. RESULTS: Participants in the PTSD group evidenced greater substance use and abuse than those in the social phobia and well-adjusted groups on several dimensions and greater alcohol consumption than the depressed group. Correlation analyses suggested that most dimensions of substance abuse were related more strongly to avoidance and numbing (cluster C) symptoms than to reexperiencing and hyperarousal. CONCLUSIONS: The present findings suggest that trauma-related psychopathology may be associated with a more hazardous pattern of substance use than depression and social phobia. PMID- 20582230 TI - Matrix strains induced by cells: Computing how far cells can feel. AB - Many tissue cells exert contractile forces that mechanically couples them to elastic matrices and that influence cell adhesion, cytoskeletal organization, and even cell differentiation. However, strains within the depths of matrices are often unclear and are likely relevant not only to the fact that some matrices such as so-called basement membranes are thin relative to cell dimensions but also to defining how far cells can 'feel'. Here we briefly present experimental results for cell spreading on thin, ligand-coated gels and for prestress in stem cells in relation to gel stiffness. We then introduce a finite element computation in which a cell is placed on an elastic matrix, while matrix elasticity and thickness are varied in order to compute and compare elastostatic deformations within the matrix. Average interfacial strains between cell and matrix show large deviations only when soft matrices are a fraction of the height and width of a cell, proving consistent with experiments. Three-dimensional (3D) cell morphologies that model stem cell-derived neurons, myoblasts, and osteoblasts show that a cylinder-shaped myoblast induces the highest strains, consistent with the prominent contractility of muscle. Groups of such cells show a weak crosstalk in matrix strains, but the cells must be much closer than a cell width. Cells thus feel on length scales closer to that of adhesions than on cellular scales or higher. PMID- 20582232 TI - One Germany, Two Worlds of Housework? Examining Employed Single and Partnered Women in the Decade after Unification. PMID- 20582231 TI - Parents' Incomes and Children's Outcomes: A Quasi-Experiment. AB - We examine the role that an exogenous increase in household income due to a government transfer unrelated to household characteristics plays in children's long run outcomes. Children in affected households have higher levels of education in their young adulthood and a lower incidence of criminality for minor offenses. Effects differ by initial household poverty status. An additional $4000 per year for the poorest households increases educational attainment by one year at age 21 and reduces having ever committed a minor crime by 22% at ages 16-17. Our evidence suggests that improved parental quality is a likely mechanism for the change. PMID- 20582234 TI - Gold-Based Magneto/Optical Nanostructures: Challenges for In Vivo Applications in Cancer Diagnostics and Therapy. AB - Nanoparticles with gold shell and iron core have unique optical and magnetic properties which can be utilized for simultaneous detection and treatment strategies. Several nanoparticles have been synthesized and shown to mediate a variety of potential applications in biomedicine, including cancer molecular optical and magnetic resonance imaging, controlled drug delivery, and photothermal ablation therapy. However, to be effective, these nanoparticles must be delivered efficiently into their targets. In this review, we will provide an updated summary of the gold-shelled magnetic nanoparticles that have been synthesized, methods for characterization, and their potential for cancer diagnosis and treatment. We will also discuss the biological barriers that need to be overcome for the effective delivery of these nanoparticles. The desired nanoparticle characteristics needed to evade these biological barriers were also explained. Hopefully, this review will help researchers in designing nanoparticles by carefully choosing the optimum size, shape, surface charge, and surface coating. PMID- 20582233 TI - Mechanisms of self-nonself discrimination and possible clinical relevance. AB - This review discusses different mechanisms that result in immunological tolerance, such as intrathymic deletion of immature T cells, intrathymic and extrathymic generation of regulatory T cells, effector mechanisms of regulatory T cells as well as molecular pathways involved in extrathymic generation of regulatory T cells in vivo and in vitro. These molecular mechanisms should enable investigators to develop clinical protocols aiming at the specific prevention of unwanted immune responses, thereby replacing indiscriminate immunosuppression that often has fatal consequences. PMID- 20582235 TI - Activation of lecithin:cholesterol acyltransferase by HDL ApoA-I central helices. AB - Lecithin:cholesterol acyltransferase (LCAT) is an enzyme that first hydrolyzes the sn-2 position of phospholipids, preferentially a diacylphosphocholine, and then transfers the fatty acid to cholesterol to yield a cholesteryl ester. HDL ApoA-I is the principal catalytic activator for LCAT. Activity of LCAT on nascent or lipid-poor HDL particles composed of phospholipid, cholesterol and ApoA-I allows the maturation of HDL particles into lipid-rich spherical particles that contain a core of cholesteryl ester surrounded by phospholipid and ApoA-I on the surface. This article reviews the recent progress in elucidating structural aspects of the interaction between LCAT and ApoA-I. In the last decade, there has been considerable progress in understanding the structure of ApoA-I and the central helices 5, 6, and 7 that are known to activate LCAT. However, much less information has been forthcoming describing the 3D structure and conformation of LCAT required to catalyze two separate reactions within a single monomeric peptide. PMID- 20582237 TI - Investigation of Sparse Data Mouse Imaging Using Micro-CT with a Carbon-Nanotube Based X-ray Source. AB - There has been a renewed interest in algorithm development for image reconstruction from highly incomplete data in computed tomography (CT). Such algorithms may lead to reduced imaging dose and time, and to the design of innovative configurations tailored to specific imaging tasks. In recent years, a carbon-nanotube (CNT)-based field-emission x-ray source has been developed, which offers easy electronic control of radiation and thus can be an ideal candidate for gated imaging. We have recently proposed algorithms for image reconstruction from fan- and cone-beam data collected at highly sparse angular views through minimization of the total-variation (TV) of the image subject to the condition that the estimated data are consistent with the measured data. In this work, we investigate and demonstrate the application of the TV-minimization algorithm to reconstructing images from mouse data acquired with a CNT-based CT scanner at a number of views much lower than what is used in conventional CT imaging. The results demonstrate that the TV-minimization algorithm can yield images with quality comparable to those obtained from a large number of views by use of the conventional algorithms. The significance of the work may lie in that the substantial reduction of projection views promised by the TV-minimization algorithm can be exploited for reducing imaging dose and time or for improving temporal resolution in tasks such as dynamic imaging. PMID- 20582236 TI - Novel Objective Biomarkers of Alcohol Use: Potential Diagnostic and Treatment Management Tools in Dual Diagnosis Care. AB - Alcohol use disorders are highly prevalent conditions that generate a large fraction of the total public health burden. These disorders are concentrated in mentally ill populations, in which reliability of self-reporting of alcohol consumption may be especially compromised. The application of objective biomarkers for alcohol use may therefore play an important role in these patients. This article provides a description and comparative overview of traditional versus novel biomarkers of alcohol consumption. Greater professional familiarity with and use of novel biomarkers as diagnostic and treatment management tools may enhance clinical standards and research on alcohol use in patients with a dual diagnosis. PMID- 20582238 TI - A Review of Acculturation Measures and Their Utility in Studies Promoting Latino Health. AB - The authors reviewed the acculturation literature with the goal of identifying measures used to assess acculturation in Hispanic populations in the context of studies of health knowledge, attitudes, and behavior change. Twenty-six acculturation measures were identified and summarized. As the Hispanic population continues to grow in the United States, there is a need to develop rigorous acculturation measures that include health indicators. Findings suggest that multidimensional acculturation scales are robust measurement tools when assessing nationality, cultural awareness, media and language preferences, and health status. Furthermore, aspects of Hispanic cultural lifestyle, such as beliefs about nutrition and physical activity, affect health care utilization, treatment, and prevention. Health communication researchers should consider aspects of cultural values and beliefs, and their impact on health status, for future research and health promotion interventions. PMID- 20582239 TI - Bioinformatic Identification of Novel Methyltransferases. AB - Methylation of DNA, protein, and even RNA species are integral processes in epigenesis. Enzymes that catalyze these reactions using the donor S adenosylmethionine fall into several structurally distinct classes. The members in each class share sequence similarity that can be used to identify additional methyltransferases. Here, we characterize these classes and in silico approaches to infer protein function. Computational methods such as hidden Markov model profiling and the Multiple Motif Scanning program can be used to analyze known methyltransferases and relay information into the prediction of new ones. In some cases, the substrate of methylation can be inferred from hidden Markov model sequence similarity networks. Functional identification of these candidate species is much more difficult; we discuss one biochemical approach. PMID- 20582241 TI - Use of carboxymethyl cellulose and collagen carrier with equine bone lyophilisate suggests late onset bone regenerative effect in a humerus drill defect - a pilot study in six sheep. AB - We assessed the use of a filler compound together with the osteoinductive demineralized bone matrix (DBM), Colloss E. The filler was comprised of carboxymethyl-cellulose and collagen type 1. The purpose of the study was to see if the filler compound would enhance the bone formation and distribute the osteoinductive stimulus throughout the bone defect. Six sheep underwent a bilateral humerus drill defect. The drill hole was filled with a compound consisting of 100 mg CMC, 100 mg collagen powder, and 1 ccm autologous full blood in one side, and a combination of this filler compound and 20 mg Colloss E in the other. The animals were divided into three groups of two animals and observed for 8, 12 and 16 weeks. Drill holes was evaluated using quantitative computed tomography (QCT), micro computed tomography (microCT) and histomorphometry. Mean total bone mineral density (BMD) of each implantation site was calculated with both QCT and microCT. Bone volume to total volume (BV/TV) was analyzed using microCT and histomorphometry. Although not statistically significant, results showed increased bone BMD after 16 weeks in microCT data and an increased BV/TV after 16 weeks in both microCT and histology. Correlation between QCT and microCT was R(2) = 0.804. Correlation between histomorphometry and microCT BV/TV data was R(2) = 0.8935 and with an average overrepresentation of 8.2% in histomorphometry. In conclusion the CMC-Collagen + Colloss E filler seems like a viable osteogenic bone filler mid- to long term. A correlation was found between the analytical methods used in this study. PMID- 20582240 TI - Basic science considerations in primary total hip replacement arthroplasty. AB - Total Hip Replacement is one of the most common operations performed in the developed world today. An increasingly ageing population means that the numbers of people undergoing this operation is set to rise. There are a numerous number of prosthesis on the market and it is often difficult to choose between them. It is therefore necessary to have a good understanding of the basic scientific principles in Total Hip Replacement and the evidence base underpinning them. This paper reviews the relevant anatomical and biomechanical principles in THA. It goes on to elaborate on the structural properties of materials used in modern implants and looks at the evidence base for different types of fixation including cemented and uncemented components. Modern bearing surfaces are discussed in addition to the scientific basis of various surface engineering modifications in THA prostheses. The basic science considerations in component alignment and abductor tension are also discussed. A brief discussion on modular and custom designs of THR is also included. This article reviews basic science concepts and the rationale underpinning the use of the femoral and acetabular component in total hip replacement. PMID- 20582242 TI - What is a Successful Outcome Following Reverse Total Shoulder Arthroplasty? AB - BACKGROUND: With variations in joint destruction, patient expectations and health status, it can be difficult to interpret outcomes following arthroplasty. The purpose of this study was to determine the relationships between different outcome indicators in 44 patients followed for two years after a reverse shoulder arthroplasty. METHODS: Prospectively collected outcomes included the Constant Murley score, Simple Shoulder Test (SST), range of motion (ROM), strength, patient satisfaction with their care and independent clinician case-review to determine global clinical outcome. Continuous outcomes were divided in two subgroups according to definitions of functional outcomes. Cohen's kappa was used to evaluate agreement between outcomes. Pearson correlations were used to quantify interrelationships. RESULTS: Although 93% of patients were substantially satisfied, fewer had good results on the other outcomes: 68% on global clinical outcome, 46% on SST and 73% on Constant-Murley score. The SST demonstrated better than chance agreement with Constant-Murley score, ROM in flexion, abduction and external rotation, and strength in external rotation. No agreement between satisfaction and other outcomes were observed. Significant correlations were observed between Constant-Murley score and SST (r = 0.78). The Constant-Murley score and SST demonstrated variable correlation with ROM and strength in flexion, abduction, internal and external rotation (0.38 < r < 0.73); the highest correlations being observed with shoulder elevation ROM (r > 0.50). CONCLUSIONS: Results show that outcome varies according to patient perspective and assessment methods. Patient satisfaction with their care was related to neither self reported nor physical impairment outcomes. Positive patient ratings of satisfaction may not necessarily be evidence of positive outcomes. PMID- 20582243 TI - Cognitive Behavioral Principles Within Group Mentoring: A Randomized Pilot Study. AB - This study evaluated the effectiveness of a group mentoring program that included components of empirically supported mentoring and cognitive behavioral techniques for children served at a community mental health center. Eighty-six 8- to 12-year old children were randomly assigned to either group mentoring or a wait-list control group. Group mentoring significantly increased children's reported social problem-solving skills and decreased parent-reported child externalizing and internalizing behavior problems after controlling for other concurrent mental health services. Attrition from the group mentoring program was notably low (7%) for children. The integration of a cognitive behavioral group mentoring program into children's existing community mental health services may result in additional reductions in externalizing and internalizing behavior problems. PMID- 20582244 TI - Smart technology for global access to healthcare. PMID- 20582245 TI - A Variance Analysis for POMDP Policy Evaluation. AB - Partially Observable Markov Decision Processes have been studied widely as a model for decision making under uncertainty, and a number of methods have been developed to find the solutions for such processes. Such studies often involve calculation of the value function of a specific policy, given a model of the transition and observation probabilities, and the reward. These models can be learned using labeled samples of on-policy trajectories. However, when using empirical models, some bias and variance terms are introduced into the value function as a result of imperfect models. In this paper, we propose a method for estimating the bias and variance of the value function in terms of the statistics of the empirical transition and observation model. Such error terms can be used to meaningfully compare the value of different policies. This is an important result for sequential decision-making, since it will allow us to provide more formal guarantees about the quality of the policies we implement. To evaluate the precision of the proposed method, we provide supporting experiments on problems from the field of robotics and medical decision making. PMID- 20582246 TI - CAVITATION OF THE GHON FOCUS IN AN HIV-INFECTED INFANT WHO ACQUIRED TUBERCULOSIS AFTER THE INITIATION OF HAART. AB - Tuberculosis immune reconstitution inflammatory syndrome (IRIS) may present as new or worsening cavitation. We present an HIV-infected infant in whom TB infection and subsequent cavitation of the Ghon focus appeared to coincide with immune reconstitution due to highly active antiretroviral therapy (HAART). TB IRIS in response to infection that occurs after starting HAART has not previously been described. PMID- 20582247 TI - Sex differences in visceral adipose tissue post-bariatric surgery compared to matched non-surgical controls. AB - OBJECTIVE AND METHODS: Given the profound weight loss after gastric banding and bypass we compared fat compartmentalization by whole body magnetic resonance imaging in women and men after these procedures to two groups of non-surgical controls who were either matched for age, weight and height or were of lower body mass index (BMI). RESULT: In women post-surgery (n=17; BMI 31.7 kg/m(2)) there was lower visceral adipose tissue (VAT) (1.4 vs 2.5 kg; P<0.01) compared with matched controls (n=59; BMI 32.1 kg/m(2)). In contrast, VAT (5.3 vs 5.4 kg) was nearly identical in men post-surgery (n=10; BMI 34.1 kg/m(2)) compared with matched controls (n=10; BMI 32.1 kg/m(2)) even though the degree of weight reduction was not significantly different from women (27.4 vs 32.6%). Furthermore, VAT when adjusted for total adipose tissue (TAT) was 43% less in women post-surgery (1.2 vs 2.1 kg; P=0.03) than in controls with lower BMI (25.1 kg/m(2)). After adjustment for TAT, subcutaneous adipose tissue in women post surgery was significantly greater than matched controls (35.1 vs 34.2 kg; P=0.03). There was a significant negative correlation of VAT and the degree of weight loss in women (r=-0.57; P=0.018) but this relationship was not significant in men (r=-0.39; P=0.27). Skeletal muscle was lower in both sexes compared with matched controls (women, 21.8 vs 23.1 kg; men, 32.5 vs 35.5 kg). CONCLUSION: Prospective studies are necessary to confirm if there is a sexual dimorphism in the effects of bariatric surgery on body composition. PMID- 20582248 TI - SOURCES OF THE ARCTIC FLORA: ORIGINS OF ARCTIC SPECIES IN RANUNCULUS AND RELATED GENERA. AB - The arctic biome is a relatively young ecosystem with ~2300 species of vascular plants. We studied the genus Ranunculus as an example of the origin and evolution of the arctic flora. For this purpose we used molecular phylogenetic and clock analyses based on evaluation of nuclear ITS and chloroplast matK-trnK DNA sequences in 194 taxa of Ranunculus and closely related genera. Taxa occurring in the Arctic arose form seven phylogenetic lineages of Ranunculus and also in the genera Coptidium and Halerpestes. Two clades of Ranunculus are species-rich in the Arctic, i.e., Ranunculus sect. Ranunculus and R. sect. Auricomus (both from R. subg. Ranunculus), but this is due to a number of arctic "microtaxa" morphologically barely separate from R. acris in the former clade and the widely agamospermic species complex of R. auricomus in the latter. Lineages with species adapted to wetlands or aquatic habitats are significant groups represented in the arctic flora (R. subg. Ranunculus sectt. Flammula and Hecatonia/Xanthobatrachium, R. subg. Batrachium, genus Coptidium) but show no clear signs of radiation in the Arctic or the northern boreal zone, except for sectt. Hecatonia/Xanthobatrachium, with R. hyperboreus and R. sceleratus subsp. reptabundus. Astonishingly few of the otherwise numerous lineages of Ranunculus with distributions in the higher mountain systems of Eurasia and North America have acted as "founding sources" for the arctic flora. The only clear example is that of the arctic-alpine R. glacialis and the Beringian R. chamissonis from the lineage of subg. R. sectt. Aconitifolii/Crymodes, although there might be others in sect. Auricomus not recovered in the current molecular data. Lineages that gave rise to arctic taxa diverged from each other from the early Miocene (R. glacialis/R. chamissonis, Coptidium, lineages in Halerpestes) and continued at an even rate throughout the Tertiary. There are no signs that the intense climate changes of the late Pliocene and the Quaternary substantially accelerated or impeded diversification in Ranunculus. Only the crown group split of R. acris and its relatives is clearly of Quaternary age. A detailed comparison concerning morphology, karyology, and life form excludes fundamental differences between taxa of Ranunculus in the Arctic and their respective closest relatives in regions south of it. Ecological traits, e.g., preferences for dry or moist soils or growth in open and sheltered conditions, also do not differ between arctic and nonarctic taxa. Migration into the Arctic thus started from different phylogenetic lineages and at different times, without development of obvious special traits in the adaptation to arctic environments. This recurrent pattern in Ranunculus differs from that seen in other arctic genera, e.g., Artemisia, in which special traits of adaptation to arctic environments are found. In Ranunculus, the origin of the open arctic biome primarily favored range expansions of taxa/species already adapted to wet habitats in cold areas and depending on rapid dispersal. PMID- 20582249 TI - Easing semantically enriched information retrieval-An interactive semi-automatic annotation system for medical documents. AB - Mapping medical concepts from a terminology system to the concepts in the narrative text of a medical document is necessary to provide semantically accurate information for further processing steps. The MetaMap Transfer (MMTx) program is a semantic annotation system that generates a rough mapping of concepts from the Unified Medical Language System (UMLS) Metathesaurus to free medical text, but this mapping still contains erroneous and ambiguous bits of information. Since manually correcting the mapping is an extremely cumbersome and time-consuming task, we have developed the MapFace editor.The editor provides a convenient way of navigating the annotated information gained from the MMTx output, and enables users to correct this information on both a conceptual and a syntactical level, and thus it greatly facilitates the handling of the MMTx program. Additionally, the editor provides enhanced visualization features to support the correct interpretation of medical concepts within the text. We paid special attention to ensure that the MapFace editor is an intuitive and convenient tool to work with. Therefore, we recently conducted a usability study in order to create a well founded background serving as a starting point for further improvement of the editor's usability. PMID- 20582250 TI - EFFECT OF PHALLOIDIN ON FILAMENTS POLYMERIZED FROM HEART MUSCLE ADP-ACTIN MONOMERS. AB - The effect of phalloidin on filaments polymerized from ADP-actin monomers of the heart muscle was investigated with differential scanning calorimetry. Heart muscle contains alpha-skeletal and alpha-cardiac actin isoforms. In the absence of phalloidin the melting temperature was 55 degrees C for the alpha-cardiac actin isoform and 58 degrees C for the alpha-skeletal one when the filaments were generated from ADP-actin monomers. After the binding of phalloidin the melting temperature was isoform independent (85.5 degrees C). We concluded that phalloidin stabilized the actin filaments of alpha-skeletal and alpha-cardiac actin isoforms to the same extent when they were polymerized from ADP-actin monomers. PMID- 20582251 TI - Tinted windshield and its effects on aging drivers' visual acuity and glare response. AB - Increasingly, automobile designers are utilizing tinted glasses for concept cars, specialty models, or to differentiate their vehicles. The objective of this study was to assess whether alternating different tinted windshields would affect aging drivers' visual acuity and glare response. Two commercially available windshields (bluish and greenish with same transmittance) were compared. The tests of visual acuity, contrast threshold, glare detection, and discomfort glare rating were performed to address the windshield effects on both the older and younger populations. Fourteen elderly and seven young individuals participated in the study. The results indicated that alternating between the tested tinted windshields would not affect drivers' visual performance for both age groups. The implications and future research are discussed. PMID- 20582252 TI - Effects of planar and non-planar driver-side mirrors on age-related discomfort glare responses. AB - In this study, we evaluated subjective nighttime discomfort-glare responses on three different types of planar and non-planar driver-side mirrors on two age groups. Fifty-six individuals (28 young [18-35 years] and 28 old [65 years and over]) participated in this experiment. Subjective discomfort-glare rating scores on three different types of driver-side mirrors were assessed utilizing De Boer's rating scale in a controlled nighttime driving environment (laboratory ambient illuminant level-l lux with headlight turned off). Three driver-side mirrors included planar "flat mirror": radius of curvature 242650.92 mm, reflectivity 0.60114, and surface reflectance 0.60568; "curved mirror": radius of curvature 1433.3 mm, reflectivity 0.21652, and surface reflectance 0.58092; "blue mirror": radius of curvature 1957.1 mm, reflectivity 0.25356, and surface reflectance 0.54585. The results indicated that with the same glare level (as measured by angle of incidence and illuminance in front of the eyes), older adults reported worse feelings of glare than their younger counterparts. Furthermore, the results indicated that both young and older adults reported worse feelings of glare for planar driver-side mirror than non-planar driver-side mirrors. These results suggest that older adults' criterion of discomfort-glare is more sensitive than their younger counterparts, and importantly, the non-planar driver-side mirrors can be beneficial in terms of reducing nighttime discomfort-glare for both the young and the elderly. PMID- 20582253 TI - Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms. AB - Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT) membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse. PMID- 20582254 TI - Relationship between age-related gait adaptations and required coefficient of friction. AB - A laboratory study was conducted to evaluate if age-related gait adaptations in walking velocity, step length and heel contact velocity could adversely influence friction demand characteristics (i.e. RCOF) and the likelihood of slip initiation. Additionally, relationship between transitional acceleration of the whole body center-of-mass (COM) and friction demand was assessed between young and older participants. Fourteen younger (7 females and 7 males, 18-30 years old) and 14 older (7 females and 7 males, over 65 years old) adults participated in the study. While wearing a safety harness, all participants walked at their preferred gait speed for approximately 20 min on the linear walking track, and synchronized ground reaction forces and posture data were captured using the force plates and six infrared cameras, respectively.The results indicated that older adults walked slower with slower heel contact velocity, and produced lower friction demand (i.e. RCOF) in comparison to younger adults. However, ANCOVA indicated that the differences in heel contact velocity between the two age groups were due to effects of walking velocity. The multiple regression and bivariate regression analyses suggested that, for older adults, heel contact velocity was a predictor for the RCOF, whereas, for younger adults, walking velocity, step length and transitional acceleration of the whole body COM were the factors contributing to the RCOF.In conclusion, the present study suggested that gait adaptations among the elderly must be considered when predicting the likelihood of slip initiation. PMID- 20582255 TI - A novel analytic measure for the water maze utilizing the concept of entropy. PMID- 20582256 TI - Decisions of voluntary action: what vs when. PMID- 20582257 TI - Forget before you remember: dynamic mechanism of memory decay and retrieval. PMID- 20582258 TI - "Apneas" in Purkinje cell activity: evidence for the bistability of membrane potential in the awake cat cerebellum. PMID- 20582259 TI - The attentional selection in visual search within short-term memory representations. PMID- 20582260 TI - The behavioral relevance of multisensory neural response interactions. AB - Sensory information can interact to impact perception and behavior. Foods are appreciated according to their appearance, smell, taste and texture. Athletes and dancers combine visual, auditory, and somatosensory information to coordinate their movements. Under laboratory settings, detection and discrimination are likewise facilitated by multisensory signals. Research over the past several decades has shown that the requisite anatomy exists to support interactions between sensory systems in regions canonically designated as exclusively unisensory in their function and, more recently, that neural response interactions occur within these same regions, including even primary cortices and thalamic nuclei, at early post-stimulus latencies. Here, we review evidence concerning direct links between early, low-level neural response interactions and behavioral measures of multisensory integration. PMID- 20582261 TI - A tactile P300 brain-computer interface. AB - In this study, we investigated a Brain-Computer Interface (BCI) based on EEG responses to vibro-tactile stimuli around the waist. P300 BCIs based on tactile stimuli have the advantage of not taxing the visual or auditory system and of being potentially unnoticeable to other people. A tactile BCI could be especially suitable for patients whose vision or eye movements are impaired. In Experiment 1, we investigated its feasibility and the effect of the number of equally spaced tactors. Whereas a large number of tactors is expected to enhance the P300 amplitude since the target will be less frequent, it could also negatively affect the P300 since it will be difficult to identify the target when tactor density increases. Participants were asked to attend to the vibrations of a target tactor, embedded within a stream of distracters. The number of tactors was two, four or six. We demonstrated the feasibility of a tactile P300 BCI. We did not find a difference in SWLDA classification performance between the different numbers of tactors. In a second set of experiments we reduced the stimulus onset asynchrony (SOA) by shortening the on- and/or off-time of the tactors. The SOA for an optimum performance as measured in our experiments turned out to be close to conventional SOAs of visual P300 BCIs. PMID- 20582262 TI - Deletion of P2X2 and P2X3 receptor subunits does not alter motility of the mouse colon. AB - Purinergic P2X receptors contribute to neurotransmission in the gut. P2X receptors are ligand-gated cation channels that mediate synaptic excitation in subsets of enteric neurons. The present study evaluated colonic motility in vitro and in vivo in wild type (WT) and P2X2 and P2X3 subunit knockout (KO) mice. The muscarinic receptor agonist, bethanechol (0.3-3 muM), caused similar contractions of the longitudinal muscle in colon segments from WT, P2X2 and P2X3 subunit KO mice. Nicotine (1-300 muM), acting at neuronal nicotinic receptors, caused similar longitudinal muscle relaxations in colonic segments from WT and P2X2 and P2X3 subunit KO mice. Nicotine-induced relaxations were inhibited by nitro-l arginine (NLA, 100 muM) and apamin (0.1 muM) which block inhibitory neuromuscular transmission. ATP (1-1000 muM) caused contractions only in the presence of NLA and apamin. ATP-induced contractions were similar in colon segments from WT, P2X2 and P2X3 KO mice. The mouse colon generates spontaneous migrating motor complexes (MMCs) in vitro. The MMC frequency was higher in P2X2 KO compared to WT tissues; other parameters of the MMC were similar in colon segments from WT, P2X2 and P2X3 KO mice. 5-Hydroxytryptophan-induced fecal output was similar in WT, P2X2 and P2X3 KO mice. These data indicate that nicotinic receptors are located predominately on inhibitory motor neurons supplying the longitudinal muscle in the mouse colon. P2X2 or P2X3 subunit containing receptors are not localized to motor neurons supplying the longitudinal muscle. Synaptic transmission mediated by P2X2 or P2X3 subunit containing receptors is not required for propulsive motility in the mouse colon. PMID- 20582263 TI - Exciting news from the adult mouse subventricular zone. PMID- 20582264 TI - What happens to olfaction without adult neurogenesis? PMID- 20582265 TI - Headlong into a genomic singularity. PMID- 20582266 TI - Impact of RNA editing on functions of the serotonin 2C receptor in vivo. AB - Transcripts encoding 5-HT(2C) receptors are modified posttranscriptionally by RNA editing, generating up to 24 protein isoforms. In recombinant cells, the fully edited isoform, 5-HT(2C-VGV), exhibits blunted G-protein coupling and reduced constitutive activity. The present studies examine the signal transduction properties of 5-HT(2C-VGV) receptors in brain to determine the in vivo consequences of altered editing. Using mice solely expressing the 5-HT(2C-VGV) receptor (VGV/Y), we demonstrate reduced G-protein coupling efficiency and high affinity agonist binding of brain 5-HT(2C-VGV) receptors. However, enhanced behavioral sensitivity to a 5-HT(2C) receptor agonist was also seen in mice expressing 5-HT(2C-VGV) receptors, an unexpected finding given the blunted G protein coupling. In addition, mice expressing 5-HT(2C-VGV) receptors had greater sensitivity to a 5-HT(2C) inverse agonist/antagonist enhancement of dopamine turnover relative to wild-type mice. These behavioral and biochemical results are most likely explained by increases in 5-HT(2C) receptor binding sites in the brains of mice solely expressing 5-HT(2C-VGV) receptors. We conclude that 5-HT(2C VGV) receptor signaling in brain is blunted, but this deficiency is masked by a marked increase in 5-HT(2C) receptor binding site density in mice solely expressing the VGV isoform. These findings suggest that RNA editing may regulate the density of 5-HT(2C) receptor binding sites in brain. We further caution that the pattern of 5-HT(2C) receptor RNA isoforms may not reflect the pattern of protein isoforms, and hence the inferred overall function of the receptor. PMID- 20582267 TI - Behavioral assessments for pre-clinical pharmacovigilance. PMID- 20582268 TI - Electric stimulation with sinusoids and white noise for neural prostheses. AB - We are investigating the use of novel stimulus waveforms in neural prostheses to determine whether they can provide more precise control over the temporal and spatial pattern of elicited activity as compared to conventional pulsatile stimulation. To study this, we measured the response of retinal ganglion cells to both sinusoidal and white noise waveforms. The use of cell-attached and whole cell patch clamp recordings allowed the responses to be observed without significant obstruction from the stimulus artifact. Electric stimulation with sinusoids elicited robust responses. White noise analysis was used to derive the linear kernel for the ganglion cell's spiking response as well as for the underlying excitatory currents. These results suggest that in response to electric stimulation, presynaptic retinal neurons exhibit bandpass filtering characteristics with a peak response that occurs 25 ms after onset. The experimental approach demonstrated here may be useful for studying the temporal response properties of other neurons in the CNS. PMID- 20582269 TI - Design challenges of implantable pressure monitoring system. AB - Pressure in various organs and body parts, such as blood vessels, heart, brain, eyes, bladder and GI tracts, is an important indication of health. Long term, continuous pressure monitoring is critically needed for a number of applications. When combined with existing neuro-prosthetics devices, they may provide better solutions to many neural disorders. First efforts toward a long-term implantable pressure monitoring system were initiated more than 40 years ago. However, a reliable, safe and implantable pressure sensor for long-term applications is not yet commercially available. This paper attempts to reveal the design challenges associated with the development of a long-term implantable pressure sensor. PMID- 20582270 TI - Statistical learning analysis in neuroscience: aiming for transparency. AB - Encouraged by a rise of reciprocal interest between the machine learning and neuroscience communities, several recent studies have demonstrated the explanatory power of statistical learning techniques for the analysis of neural data. In order to facilitate a wider adoption of these methods, neuroscientific research needs to ensure a maximum of transparency to allow for comprehensive evaluation of the employed procedures. We argue that such transparency requires "neuroscience-aware" technology for the performance of multivariate pattern analyses of neural data that can be documented in a comprehensive, yet comprehensible way. Recently, we introduced PyMVPA, a specialized Python framework for machine learning based data analysis that addresses this demand. Here, we review its features and applicability to various neural data modalities. PMID- 20582271 TI - The hybrid BCI. AB - Nowadays, everybody knows what a hybrid car is. A hybrid car normally has two engines to enhance energy efficiency and reduce CO2 output. Similarly, a hybrid brain-computer interface (BCI) is composed of two BCIs, or at least one BCI and another system. A hybrid BCI, like any BCI, must fulfill the following four criteria: (i) the device must rely on signals recorded directly from the brain; (ii) there must be at least one recordable brain signal that the user can intentionally modulate to effect goal-directed behaviour; (iii) real time processing; and (iv) the user must obtain feedback. This paper introduces hybrid BCIs that have already been published or are in development. We also introduce concepts for future work. We describe BCIs that classify two EEG patterns: one is the event-related (de)synchronisation (ERD, ERS) of sensorimotor rhythms, and the other is the steady-state visual evoked potential (SSVEP). Hybrid BCIs can either process their inputs simultaneously, or operate two systems sequentially, where the first system can act as a "brain switch". For example, we describe a hybrid BCI that simultaneously combines ERD and SSVEP BCIs. We also describe a sequential hybrid BCI, in which subjects could use a brain switch to control an SSVEP-based hand orthosis. Subjects who used this hybrid BCI exhibited about half the false positives encountered while using the SSVEP BCI alone. A brain switch can also rely on hemodynamic changes measured through near-infrared spectroscopy (NIRS). Hybrid BCIs can also use one brain signal and a different type of input. This additional input can be an electrophysiological signal such as the heart rate, or a signal from an external device such as an eye tracking system. PMID- 20582272 TI - Exploring the function of neural oscillations in early sensory systems. AB - Neuronal oscillations appear throughout the nervous system, in structures as diverse as the cerebral cortex, hippocampus, subcortical nuclei and sense organs. Whether neural rhythms contribute to normal function, are merely epiphenomena, or even interfere with physiological processing are topics of vigorous debate. Sensory pathways are ideal for investigation of oscillatory activity because their inputs can be defined. Thus, we will focus on sensory systems as we ask how neural oscillations arise and how they might encode information about the stimulus. We will highlight recent work in the early visual pathway that shows how oscillations can multiplex different types of signals to increase the amount of information that spike trains encode and transmit. Last, we will describe oscillation-based models of visual processing and explore how they might guide further research. PMID- 20582273 TI - mGluR(1) Receptors Contribute to Non-Purinergic Slow Excitatory Transmission to Submucosal VIP Neurons of Guinea-Pig Ileum. AB - Vasoactive intestinal peptide (VIP) immunoreactive secretomotor neurons in the submucous plexus are involved in mediating bacterial toxin-induced hypersecretion leading to diarrhoea. VIP neurons become hyperexcitable after the mucosa is exposed to cholera toxin, which suggests that the manipulation of the excitability of these neurons may be therapeutic. This study used standard intracellular recording methods to systematically characterize slow excitatory postsynaptic potentials (EPSPs) evoked in submucosal VIP neurons by different stimulus regimes (1, 3 and 15 pulse 30 Hz stimulation), together with their associated input resistances and pharmacology. All slow EPSPs were associated with a significant increase in input resistance compared to baseline values. Slow EPSPs evoked by a single stimulus were confirmed to be purinergic, however, slow EPSPs evoked by 15 pulse trains were non-purinergic and those evoked by 3 pulse trains were mixed. NK(1) or NK(3) receptor antagonists did not affect slow EPSPs. The group I mGluR receptor antagonist, PHCCC reduced the amplitude of purinergic and non-purinergic slow EPSPs. Blocking mGluR(1) receptors depressed the overall response to 3 and 15 pulse trains, but this effect was inconsistent, while blockade of mGluR(5) receptors had no effect on the non-purinergic slow EPSPs. Thus, although other receptors are almost certainly involved, our data indicate that there are at least two pharmacologically distinct types of slow EPSPs in the VIP secretomotor neurons: one mediated by P2Y receptors and the other in part by mGluR(1) receptors. PMID- 20582274 TI - Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala. AB - A common characteristic of irritable bowel syndrome (IBS) is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI) tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic pituitary-adrenal axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor and glucocorticoid receptor-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS. PMID- 20582275 TI - The cornucopia of intestinal chemosensory transduction. AB - The chemosensory transduction mechanisms that the gastrointestinal (GI) tract uses to detect chemical and nutrient stimuli are poorly understood. The GI tract is presented with a wide variety of stimuli including potentially harmful chemicals or toxins as well as 'normal' stimuli including nutrients, bacteria and mechanical forces. Sensory transduction is at its simplest the conversion of these stimuli into a neural code in afferent nerves. Much of the information encoded is used by the enteric nervous system to generate local reflexes while complementary information is sent to the central nervous system via afferents or by release of hormones to affect behaviour. This review focuses on the chemosensory transduction mechanisms present in the GI tract. It examines the expression and localisation of the machinery for chemosensory transduction. It summarises the types of cells which might be involved in detecting stimuli and releasing neuroactive transmitters. Finally, it highlights the idea that chemosensory transduction mechanisms in the GI tract utilise many overlapping and complementary mechanisms for detecting and transducing stimuli into reflex action. PMID- 20582276 TI - Synaptic Network Activity Induces Neuronal Differentiation of Adult Hippocampal Precursor Cells through BDNF Signaling. AB - Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potentiation (LTP)-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg(2+) free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine- and Mg(2+)-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca(2+) influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF) from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling. PMID- 20582277 TI - Additive effects of physical exercise and environmental enrichment on adult hippocampal neurogenesis in mice. AB - Voluntary physical exercise (wheel running, RUN) and environmental enrichment both stimulate adult hippocampal neurogenesis but do so by different mechanisms. RUN induces precursor cell proliferation, whereas ENR exerts a survival-promoting effect on newborn cells. In addition, continued RUN prevented the physiologically occurring age-related decline in precursor cell in the dentate gyrus but did not lead to a corresponding increase in net neurogenesis. We hypothesized that in the absence of appropriate cognitive stimuli the potential for neurogenesis could not be realized but that an increased potential by proliferating precursor cells due to RUN could actually lead to more adult neurogenesis if an appropriate survival promoting stimulus follows the exercise. We thus asked whether a sequential combination of RUN and ENR (RUNENR) would show additive effects that are distinct from the application of either paradigm alone. We found that the effects of 10 days of RUN followed by 35 days of ENR were additive in that the combined stimulation yielded an approximately 30% greater increase in new neurons than either stimulus alone, which also increased neurogenesis. Surprisingly, this result indicates that although overall the amount of proliferating cells in the dentate gyrus is poorly predictive of net adult neurogenesis, an increased neurogenic potential nevertheless provides the basis for a greater efficiency of the same survival-promoting stimulus. We thus propose that physical activity can "prime" the neurogenic region of the dentate gyrus for increased neurogenesis in the case the animal is exposed to an additional cognitive stimulus, here represented by the enrichment paradigm. PMID- 20582278 TI - Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning. AB - Adult neurogenesis replenishes olfactory bulb (OB) interneurons throughout the life of most mammals, yet during this constant flux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the sub-ventricular zone (SVZ). Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs) born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral deficit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local field potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB. PMID- 20582280 TI - Meta-analysis of kindling-induced gene expression changes in the rat hippocampus. AB - Numerous studies have been performed to examine gene expression patterns in the rodent hippocampus in the kindling model of epilepsy. However, recent reviews of this literature have revealed limited agreement among studies. Because this conclusion was based on retrospective comparison of reported "hit lists" from individual studies, we hypothesized that re-analysis of the original expression data would help address this concern. In this paper, we reanalyzed four genome wide expression studies of excitotoxin-induced kindling in rat and performed a statistical meta-analysis. The meta-analysis revealed over 800 genes which show significant change in expression 24 h after initial seizure induction, and 59 genes altered after 10 days. To evaluate our results in light of previous work, we assembled a reference list of genes formed from a consensus of the published literature. Our profiles include most of the genes in this reference list, and most of the additional genes are from pathways or biological processes previously recognized to be altered in kindling. In addition our results emphasized expression changes in lipid metabolism and protein degradation pathways. We conclude that a cautious re-analysis of published expression data can help illuminate genes and pathways underling kindling. Supplementary Material is available at http://www.chibi.ubc.ca/faculty/pavlidis/meta-analysis-of-brain kindling/ PMID- 20582281 TI - To What Extent is Blood a Reasonable Surrogate for Brain in Gene Expression Studies: Estimation from Mouse Hippocampus and Spleen. AB - Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain), it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlation between the tissues for genes that display a high heritability of expression level. This correlation is not limited to apparent expression differences caused by sequence polymorphisms in the target sequences and includes both cis and trans genetic effects. A tissue such as blood could therefore give surrogate information on expression in brain for a subset of genes, in particular those co-expressed between the two tissues, which have heritably varying expression. PMID- 20582279 TI - Wiring Olfaction: The Cellular and Molecular Mechanisms that Guide the Development of Synaptic Connections from the Nose to the Cortex. AB - Within the central nervous system, the olfactory system fascinates by its developmental and physiological particularities, and is one of the most studied models to understand the mechanisms underlying the guidance of growing axons to their appropriate targets. A constellation of contact-mediated (laminins, CAMs, ephrins, etc.) and secreted mechanisms (semaphorins, slits, growth factors, etc.) are known to play different roles in the establishment of synaptic interactions between the olfactory epithelium, olfactory bulb (OB) and olfactory cortex. Specific mechanisms of this system (including the amazing family of about 1000 different olfactory receptors) have been also proposed. In the last years, different reviews have focused in partial sights, specially in the mechanisms involved in the formation of the olfactory nerve, but a detailed review of the mechanisms implicated in the development of the connections among the different olfactory structures (olfactory epithelium, OB, olfactory cortex) remains to be written. In the present work, we afford this systematic review: the different cellular and molecular mechanisms which rule the formation of the olfactory nerve, the lateral olfactory tract and the intracortical connections, as well as the few data available regarding the accessory olfactory system. These mechanisms are compared, and the implications of the differences and similarities discussed in this fundamental scenario of ontogeny. PMID- 20582282 TI - Genetics of the hippocampal transcriptome in mouse: a systematic survey and online neurogenomics resource. AB - Differences in gene expression in the CNS influence behavior and disease susceptibility. To systematically explore the role of normal variation in expression on hippocampal structure and function, we generated an online microarray database for a diverse panel of strains of mice, including most common inbred strains and numerous recombinant inbred lines (www.genenetwork.org). Using this resource, coexpression networks for families of genes can be generated rapidly to test causal models related to function. The data set is optimized for quantitative trait locus (QTL) mapping and was used to identify over 5500 QTLs that modulate mRNA levels. We describe a wide variety of analyses and novel synthetic approaches that take advantage of this resource, and demonstrate how both the data and associated tools can be applied to the study of gene regulation in the hippocampus and relations to structure and function. PMID- 20582283 TI - Neurokinin-1 receptor activation in globus pallidus. AB - The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O2)11] substance P (SM-SP) at 1 muM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson's disease. PMID- 20582284 TI - P300-Based Brain-Computer Interface Communication: Evaluation and Follow-up in Amyotrophic Lateral Sclerosis. AB - To describe results of training and 1-year follow-up of brain-communication in a larger group of early and middle stage amyotrophic lateral sclerosis (ALS) patients using a P300-based brain-computer interface (BCI), and to investigate the relationship between clinical status, age and BCI performance. A group of 21 ALS patients were tested with a BCI-system using two-dimensional cursor movements. A four choice visual paradigm was employed to training and test the brain-communication abilities. The task consisted of reaching with the cursor one out of four icons representing four basic needs. Five patients performed a follow up test 1 year later. The clinical severity in all patients were assessed with a battery of clinical tests. A comparable control group of nine healthy subjects was employed to investigate performance differences. Nineteen patients and nine healthy subjects were able to achieve good and excellent cursor movements' control, acquiring at least communication abilities above chance level; during follow-up the patients maintained their BCI-skill. We found mild cognitive impairments in the ALS group which may be attributed to motor deficiencies, while no relevant correlation has been found between clinical data and BCI performance. A positive correlation between age and the BCI-skill in patients was found. Time since training acquisition and clinical status did not affect the patients brain communication skill at early and middle stage of the disease. A brain communication tool can be used in most ALS patients at early and middle stage of the disease before entering the locked-in stage. PMID- 20582285 TI - A Simple and Accurate onset Detection Method for a Measured Bell-shaped Speed Profile. AB - Motor control neuroscientists measure limb trajectories and extract the onset of the movement for a variety of purposes. Such trajectories are often aligned relative to the onset of individual movement before the features of that movement are extracted and their properties are inspected. Onset detection is performed either manually or automatically, typically by selecting a velocity threshold. Here, we present a simple onset detection algorithm that is more accurate than the conventional velocity threshold technique. The proposed method is based on a simple regression and follows the minimum acceleration with constraints model, in which the initial phase of the bell-shaped movement is modeled by a cubic power of the time. We demonstrate the performance of the suggested method and compare it to the velocity threshold technique and to manual onset detection by a group of motor control experts. The database for this comparison consists of simulated minimum jerk trajectories and recorded reaching movements. PMID- 20582286 TI - Offline Identification of Imagined Speed of Wrist Movements in Paralyzed ALS Patients from Single-Trial EEG. AB - The study investigated the possibility of identifying the speed of an imagined movement from EEG recordings in amyotrophic lateral sclerosis (ALS) patients. EEG signals were acquired from four ALS patients during imagination of wrist extensions at two speeds (fast and slow), each repeated up to 100 times in random order. The movement-related cortical potentials (MRCPs) and averaged sensorimotor rhythm associated with the two tasks were obtained from the EEG recordings. Moreover, offline single-trial EEG classification was performed with discrete wavelet transform for feature extraction and support vector machine for classification. The speed of the task was encoded in the time delay of peak negativity in the MRCPs, which was shorter for faster than for slower movements. The average single-trial misclassification rate between speeds was 30.4 +/- 3.5% when the best scalp location and time interval were selected for each individual. The scalp location and time interval leading to the lowest misclassification rate varied among patients. The results indicate that the imagination of movements at different speeds is a viable strategy for controlling a brain-computer interface system by ALS patients. PMID- 20582288 TI - Frequency-Domain Analysis of Intrinsic Neuronal Properties using High-Resistant Electrodes. AB - Intrinsic cellular properties of neurons in culture or slices are usually studied by the whole cell clamp method using low-resistant patch pipettes. These electrodes allow detailed analyses with standard electrophysiological methods such as current- or voltage-clamp. However, in these preparations large parts of the network and dendritic structures may be removed, thus preventing an adequate study of synaptic signal processing. Therefore, intact in vivo preparations or isolated in vitro whole brains have been used in which intracellular recordings are usually made with sharp, high-resistant electrodes to optimize the impalement of neurons. The general non-linear resistance properties of these electrodes, however, severely limit accurate quantitative studies of membrane dynamics especially needed for precise modelling. Therefore, we have developed a frequency domain analysis of membrane properties that uses a Piece-wise Non-linear Electrode Compensation (PNEC) method. The technique was tested in second-order vestibular neurons and abducens motoneurons of isolated frog whole brain preparations using sharp potassium chloride- or potassium acetate-filled electrodes. All recordings were performed without online electrode compensation. The properties of each electrode were determined separately after the neuronal recordings and were used in the frequency-domain analysis of the combined measurement of electrode and cell. This allowed detailed analysis of membrane properties in the frequency-domain with high-resistant electrodes and provided quantitative data that can be further used to model channel kinetics. Thus, sharp electrodes can be used for the characterization of intrinsic properties and synaptic inputs of neurons in intact brains. PMID- 20582287 TI - Co-expression of Argonaute2 Enhances Short Hairpin RNA-induced RNA Interference in Xenopus CNS Neurons In Vivo. AB - RNA interference (RNAi) is an evolutionarily conserved mechanism for sequence specific gene silencing. Recent advances in our understanding of RNAi machinery make it possible to reduce protein expression by introducing short hairpin RNA (shRNA) into cells of many systems, however, the efficacy of RNAi-mediated protein knockdown can be quite variable, especially in intact animals, and this limits its application. We built adaptable molecular tools, pSilencer (pSi) and pReporter (pRe) constructs, to evaluate the impact of different promoters, shRNA structures and overexpression of Ago2, the key enzyme in the RNA-induced silencing complex, on the efficiency of RNAi. The magnitude of RNAi knockdown was evaluated in cultured cells and intact animals by comparing fluorescence intensity levels of GFP, the RNAi target, relative to mCherry, which was not targeted. Co-expression of human Ago2 with shRNA significantly enhanced efficiency of GFP knockdown in cell lines and in neurons of intact Xenopus tadpoles. Human H1- and U6-promotors alone or the U6-promotor with an enhancer element were equally effective at driving GFP knockdown. shRNA derived from the microRNA-30 design (shRNA(mir30)) enhanced the efficiency of GFP knockdown. Expressing pSi containing Ago2 with shRNA increased knockdown efficiency of an endogenous neuronal protein, the GluR2 subunit of the AMPA receptor, functionally accessed by recording AMPA receptor-mediated spontaneous synaptic currents in Xenopus CNS neurons. Our data suggest that co-expression of Ago2 and shRNA is a simple method to enhance RNAi in intact animals. While morpholino antisense knockdown is effective in Xenopus and Zebrafish, a principle advantage of the RNAi method is the possibility of spatial and temporal control of protein knockdown by use of cell type specific and regulatable pol II promoters to drive shRNA and Ago2. This should extend the application of RNAi to study gene function of intact brain circuits. PMID- 20582289 TI - In Silico Enhanced Restriction Enzyme Based Methylation Analysis of the Human Glioblastoma Genome Using Agilent 244K CpG Island Microarrays. AB - Genome wide methylation profiling of gliomas is likely to provide important clues to improving treatment outcomes. Restriction enzyme based approaches have been widely utilized for methylation profiling of cancer genomes and will continue to have importance in combination with higher density microarrays. With the availability of the human genome sequence and microarray probe sequences, these approaches can be readily characterized and optimized via in silico modeling. We adapted the previously described HpaII/MspI based Methylation Sensitive Restriction Enzyme (MSRE) assay for use with two-color Agilent 244K CpG island microarrays. In this assay, fragmented genomic DNA is digested in separate reactions with isoschizomeric HpaII (methylation-sensitive) and MspI (methylation insensitive) restriction enzymes. Using in silico hybridization, we found that genomic fragmentation with BfaI was superior to MseI, providing a maximum effective coverage of 22,362 CpG islands in the human genome. In addition, we confirmed the presence of an internal control group of fragments lacking HpaII/MspI sites which enable separation of methylated and unmethylated fragments. We used this method on genomic DNA isolated from normal brain, U87MG cells, and a glioblastoma patient tumor sample and confirmed selected differentially methylated CpG islands using bisulfite sequencing. Along with additional validation points, we performed a receiver operating characteristics (ROC) analysis to determine the optimal threshold (p 120mm). A cross validation study on 14 obese subjects confirmed these observations, when the JP quadratic equations under estimated body fat predicted using dual energy x-ray absorptiometry (DXA) by 2.1% whereas our exponential power-function model was found to underestimate body fat by less than 1.0%. Otherwise, the agreement between the DXA fat (%) and the two models were found to be almost identical, with both coefficients of variation being 10.2%. CONCLUSIONS: Caution should be exercised when predicting body fat using the JP quadratic equations for subjects with sums of skinfolds>120 mm. For these subjects, we recommend estimating body fat using the tables reported in the present manuscript, based on the more biologically sound and empirically valid exponential power-function model. PMID- 20582332 TI - On habits and addiction: An associative analysis of compulsive drug seeking. AB - The processes that underlie the pathological pursuit of drugs in addiction and that support the transition from casual drug taking to their compulsive pursuit have recently been proposed to reflect the interaction of two action control processes that mediate the goal-directed and habitual control of actions for natural rewards. Here we describe the evidence for these learning processes, their associate structure and the motivational mechanisms through which their operation is translated into performance. Finally, we describe the potential changes in the interaction between habitual and goal-directed processes induced by drug addiction that subserve compulsive drug pursuit; i.e. the increase in habit learning and reduction in the regulation of habits induced by changes in the circuitry that mediates goal-directed action. PMID- 20582333 TI - In situ Materials Characterization using the Tissue Diagnostic Instrument. AB - An understanding of the mechanical behavior of polymers is critical towards the design, implementation, and quality control of such materials. Yet experiments and method for the characterization of material properties of polymers remain challenging due the need to reconcile constitutive assumptions with experimental conditions. Well-established modes of mechanical testing, such as unconfined compression or uniaxial tension, require samples with specific geometries and carefully controlled orientations. Moreover, producing specimens that conform to such specifications often requires a considerable amount of sample material. In this study we validate a micromechanical indentation device, the Tissue Diagnostic Instrument (TDI), which implements a cyclic indentation method to determine the material properties of polymers and elastomeric materials. Measurements using the TDI require little or no sample preparation, and they allow the testing of sample materials in situ. In order to validate the use of the TDI, we compared measurements of modulus determined by the TDI to those obtained by unconfined compression tests and by uniaxial tension tests within the limit of small stresses and strains. The results show that the TDI measurements were significantly correlated with both unconfined compression (p<0.001; r(2) = 0.92) and uniaxial tension tests (p<0.001; r(2)=0.87). Moreover, the measurements across all three modes of testing were statistically indistinguishable from each other (p=0.92; ANOVA) and demonstrate that TDI measurements can provide a surrogate for the conventional methods of mechanical characterization. PMID- 20582334 TI - EXTRACTING PRINCIPLE COMPONENTS FOR DISCRIMINANT ANALYSIS OF FMRI IMAGES. AB - This paper presents an approach for selecting optimal components for discriminant analysis. Such an approach is useful when further detailed analyses for discrimination or characterization requires dimensionality reduction. Our approach can accommodate a categorical variable such as diagnosis (e.g. schizophrenic patient or healthy control), or a continuous variable like severity of the disorder. This information is utilized as a reference for measuring a component's discriminant power after principle component decomposition. After sorting each component according to its discriminant power, we extract the best components for discriminant analysis. An application of our reference selection approach is shown using a functional magnetic resonance imaging data set in which the sample size is much less than the dimensionality. The results show that the reference selection approach provides an improved discriminant component set as compared to other approaches. Our approach is general and provides a solid foundation for further discrimination and classification studies. PMID- 20582336 TI - A bimetallic uranium mu-dicarbide complex: synthesis, X-ray crystal structure, and bonding. AB - The synthesis, spectroscopy, structure, and bonding of the molecular uranium dicarbide complex (mu,eta(1):eta(1)-C(2))[U(N[t-Bu]Ar)(3)](2) (Ar = 3,5 Me(2)C(6)H(3)) is described. PMID- 20582337 TI - Desorption electrospray ionization-mass spectrometry for the detection of analytes extracted by thin-film molecularly imprinted polymers. AB - Desorption electrospray ionization-mass spectrometry (DESI-MS) is a powerful technique for the analysis of solid and liquid surfaces that has found numerous applications in the few years since its invention. For the first time, it is applied to the detection of analytes extracted by molecularly imprinted polymers (MIPs) in a thin-film format. MIPs formed with 2,4-dichlorophenoxyacetic acid (2,4-D) as the template were used for the extraction of this analyte from aqueous solutions spiked at concentrations of 0.0050-2.0 mg L(-1) (approximately 2 x 10( 8) to approximately 1 x 10(-5) M). The response was linear up to 0.50 mg L(-1), and then levelled off due to saturation of the active sites of the MIP. In MS/MS mode, the signal at 0.0050 mg L(-1) was still an order of magnitude higher than the signal of a blank. The MIP DESI-MS approach was also used for the analysis of tap water and river water spiked with 2,4-D and four analogues, which indicated that these analogues were also extracted to various extents. For practical applications of the MIP, a detection technique is required that can distinguish between these structurally similar compounds, and DESI-MS fulfills this purpose. PMID- 20582335 TI - Ultrathin SmVO4 nanosheets: ionic liquid-assisted hydrothermal synthesis, characterization, formation mechanism and optical property. AB - We report on the synthesis of ultrathin SmVO(4) nanosheets through a simple and facile ionic liquid-assisted hydrothermal approach and their application in luminescence properties. The as-prepared products were characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy/high-resolution TEM, energy dispersive X-ray microanalysis, Fourier transform infrared spectrometry and photoluminescence technique. The SmVO(4) nanosheets had a tetragonal (t-) structure with the thickness of 10-20 nm and the size in the range of 10-12 microm. We found that the amount of ionic liquid, pH value and synthesizing temperature played crucial roles in controlling the structure and morphology of as-prepared samples. Particularly, the amount of ionic liquid [BMIM]Br can effectively control the shape of t-SmVO(4) nanostructures by adsorption on the (001) plane of the crystals, resulting in their preferential growth along the [100] and [010] directions via hydrogen bond co-pi-pi stack interaction. A dissolution-recrystallization process was reasonably proposed to understand the formation mechanism of t-SmVO(4) nanosheets based on the experimental results. In addition, the photoluminescence spectra reveals that the as-prepared t-SmVO(4) nanosheets exit red emission related to (4)G(5/2)-->(6)H(7/2) transition. PMID- 20582338 TI - Sorption, desorption, and surface oxidative fate of nicotine. AB - Nicotine dynamics in an indoor environment can be greatly affected by building parameters (e.g. relative humidity (RH), air exchange rate (AER), and presence of ozone), as well as surface parameters (e.g. surface area (SA) and polarity). To better understand the indoor fate of nicotine, these parameter effects on its sorption, desorption, and oxidation rates were investigated on model indoor surfaces that included fabrics, wallboard paper, and wood materials. Nicotine sorption under dry conditions was enhanced by higher SA and higher polarity of the substrate. Interestingly, nicotine sorption to cotton and nylon was facilitated by increased RH, while sorption to polyester was hindered by it. Desorption was affected by RH, AER, and surface type. Heterogeneous nicotine ozone reaction was investigated by Fourier transform infrared spectrometry with attenuated total reflection (FTIR-ATR), and revealed a pseudo first-order surface reaction rate of 0.035 +/- 0.015 min(-1) (at [O(3)] = 6 +/- 0.3 x 10(15) molecules cm(-3)) that was partially inhibited at high RH. Extrapolation to a lower ozone level ([O(3)] = 42 ppb) showed oxidation on the order of 10(-5) min( 1) corresponding to a half-life of 1 week. In addition, similar surface products were identified in dry and high RH using gas chromatography-mass spectrometry (GC MS). However, FTIR analysis revealed different product spectra for these conditions, suggesting additional unidentified products and association with surface water. Knowing the indoor fate of condensed and gas phase nicotine and its oxidation products will provide a better understanding of nicotine's impact on personal exposures as well as overall indoor air quality. PMID- 20582340 TI - A fluorescent sensor for pyrophosphate based on a Pd(II) complex. AB - A mixture of the Pd(II) complex [Pd(NO(3))(2)(bipy)] (bipy = 2,2'-bipyridine) and the fluorescent dye Methylcalcein blue (MCB) constitutes a chemosensing ensemble which can be used for the detection of pyrophosphate (PPi) by fluorescence spectroscopy. The sensor operates in buffered aqueous solution at neutral pH, and allows sensing PPi at low to mid micromolar concentrations with very good selectivity over other anions such as phosphate, acetate, nitrate, sulfate, chloride, and bicarbonate. PMID- 20582341 TI - Crossed molecular beam ion-imaging study of the Cl + SiH4 --> HCl + SiH3 reaction: product vibrational state-to-state correlation. AB - The dynamics of the Cl + SiH(4) --> HCl + SiH(3) reaction has been studied using the crossed molecular beam technique with slice imaging. The ion images of the silyl radical (SiH(3)) product from the Cl + SiH(4) reaction were recorded at different collision energies, using the (2 + 1) resonance enhanced multi-photon ionization (REMPI) technique. The product velocity and angular distributions of this reaction were determined from the recorded images. The vibrational state-to state correlation of the relative population between the two reaction products, SiH(3) and HCl, was also determined. Finally, the Cl + SiH(4) results are compared with that of the F + SiH(4) reaction. PMID- 20582342 TI - 2H NMR study of 2D melting and dynamic behaviour of CDCl3 confined in ACF nanospace. AB - Two-dimensional melting of trichloromethane (chloroform) confined in activated carbon fibre was investigated using differential thermal analysis and (2)H NMR techniques. Differential thermal analysis revealed a thermal anomaly with an endothermic peak at 269 K, which was distributed from 250 K to 287 K on the heating direction. This anomaly was also observed upon cooling at the same temperature. Furthermore, (2)H NMR revealed that slow motion such as molecular hopping and/or diffusion of CDCl(3) in ACF affected the spectral line width. The temperature dependence (Arrhenius plot) of the spectral line width showed an inflection point at 227 K. The activation energy of molecular motion of CDCl(3) in ACF was 4 kJ mol(-1) at temperatures greater than 227 K and 7.7 kJ mol(-1) at temperatures less than 227 K. Reduction of the activation energy suggests that the average intermolecular distance between CDCl(3) molecules enlarges above the inflection point. The difference of activation energy (3.7 kJ mol(-1)) is close to the enthalpy of fusion in typical plastic crystals. These results reveal that the thermal anomaly and the transition of dynamic process correspond respectively to melting of CHCl(3) in ACF and the pre-melting phenomenon. PMID- 20582339 TI - Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders. AB - Muscarinic acetylcholine receptors (mAChRs) represent exciting therapeutic targets for the treatment of multiple CNS disorders. The high degree of conservation of amino acids comprising the orthosteric acetylcholine (ACh) binding site between individual mAChR subtypes has hindered the development of subtype-selective compounds that bind to this site. As a result, many academic and industry researchers are now focusing on developing allosteric activators of mAChRs including both positive allosteric modulators (PAMs) and allosteric agonists. In the past 10 years major advances have been achieved in the discovery of allosteric ligands that possess much greater selectivity for individual mAChR subtypes when compared to previously developed orthosteric agents. These novel allosteric modulators of mAChRs may provide therapeutic potential for treatment of a number of CNS disorders such as Alzheimer's disease and schizophrenia. PMID- 20582343 TI - Coordination study of a new class of imine imidazol-2-imine ligands to titanium(IV) and palladium(II). AB - A new family of ligand precursors, N-(1-(2,6-dimethylphenylimino)ethyl)-1,3 bis(aryl)imidazol-2-imine hydrochloride, wherein aryl = 2,4,6-trimethylphenyl (3a) and 2,6-diisopropylphenyl (3b), was prepared and structurally characterised. Deprotonation of the salts yields molecules with delocalised pi-electrons, leading to zwitterionic mesomeric structures. Titanium(IV) (4a,b) and palladium(II) (5a,b) complexes were isolated and also structurally characterised. Two different coordination modes were observed where the ligand is either coordinated in a bidentate fashion as expected, or in a monodentate fashion through the more basic aryliminic nitrogen atom. PMID- 20582344 TI - Functionalisation of terpyridine complexes containing the Re(CO)3(+) moiety. AB - The investigation into the substitution and addition chemistry of Re(sigma(2) terpy)(CO)(3)Cl shows that the chloride in Re(sigma(2)-terpy)(CO)(3)Cl (1) may be substituted for acetonitrile to give [Re(sigma(2)-terpy)(CO)(3)(CH(3)CN)][PF(6)] (2), but in the cationic complex [Re(sigma(2)-terpyMe)(CO)(3)Cl][PF(6)] (4), where the pendant pyridine has been methylated, substitution of the chloride could not be achieved using standard conditions. However, use of [Re(sigma(2) terpyMe)(CO)(3)I][PF(6)] (3) results in the formation of [Re(sigma(2) terpyMe)(CO)(3)(CH(3)CN)][PF(6)](2) (5). The acetonitrile ligand in complex 2 was found to be labile and could be substituted by pyridine donors. PMID- 20582345 TI - Ultrafast Grignard addition reactions in the presence of water. AB - The addition of allylmagnesium bromide and benzylmagnesium chloride to carbonyl compounds was investigated in the presence of protic reagents such as water and the rate of carbonyl addition was found to be comparable to the rate of protonation by the reagent. PMID- 20582346 TI - Arylsilane oxidation--new routes to hydroxylated aromatics. AB - An efficient route to hydroxylated aromatics has been developed, via the oxidation of aryl organosilanes under functional group-tolerant and relatively mild conditions, using sub-stoichiometric amounts of fluoride promoters. PMID- 20582347 TI - Light-driven nanoscale chiral molecular switch: reversible dynamic full range color phototuning. AB - A light-driven nanoscale chiral molecular switch was found to impart its chirality to an achiral liquid crystal host to form a self-organized, optically tunable helical superstructure capable of fast and reversible phototuning of the structural reflection across the entire visible region. PMID- 20582348 TI - Locking an oxidation-sensitive dynamic peptide system in the gel state. AB - We describe an enzyme-driven dynamic supramolecular peptide system which displays multiple reversible pathways, giving rise to emergent properties that are dictated by environmental conditions and that can be locked in a gel-state. PMID- 20582349 TI - Three's company: co-crystallization of a self-assembled S(4) metallacyclophane with two diastereomeric metallacycle intermediates. AB - Three discrete supramolecular self-assembled arsenic(iii) complexes including an unusual S(4)-symmetric tetranuclear [As(4)L(2)Cl(4)] metallacyclophane and two diastereomeric cis/trans-[As(2)LCl(2)] metallacycle intermediates co-crystallize within a single crystal lattice. PMID- 20582350 TI - Porphyrin based molecular turnstiles. AB - Molecular turnstiles, based on a hinge composed of a Sn-porphyrin bearing coordinating sites at the meso positions and a handle, equipped with a tridentate coordinating pole or its Pd(ii) complex, connected to the porphyrin through Sn-O bonds, offering open (free rotation of the handle around the hinge) and close states (blockage of rotation through binding of Pd(ii)) were designed, prepared and studied both in solution and in the solid state. PMID- 20582351 TI - Streamlined approach to a new gelator: inspiration from solid-state interactions for a mercury-induced gelation. AB - A new gelator was discovered by identifying molecular scaffolds exhibiting 1D intermolecular interactions in the solid-state and synthesizing derivatives. Gelation can be triggered by adding Hg(OAc)(2) to a precursor molecule. The in situ gelation is selective for Hg(2+) over other metals. PMID- 20582352 TI - Revival of TE2A; a better chelate for Cu(II) ions than TETA? AB - A highly effective synthetic route for TE2A was developed and the (64)Cu-labeled TE2A complexes showed higher kinetic inertness and faster clearance than most commonly used TETA analogs. PMID- 20582353 TI - Chiral binaphthylbisbipyridine-based copper(I) coordination polymer gels as supramolecular catalysts. AB - A novel class of chiral coordination polymer organogels, with multi-stimuli responsive properties and suitable for use as catalysts in 1,3-dipolar Huisgen cycloaddition reaction, are reported. PMID- 20582354 TI - A general design platform for ionic liquid ions based on bridged multi heterocycles with flexible symmetry and charge. AB - A conceptual design platform for new ionic liquids with variable heterocycles, bridges, symmetry, and charge was developed using simple alkylation, click, and ionic liquid chemistries and demonstrated with 1-(2-(5-tetrazolidyl)ethyl)-3-(5 1H-tetrazolyl)methylimidazolium and its conversion into room-temperature ionic liquids as cation or as anion. PMID- 20582355 TI - Heterobimetallic porphyrin-based single-chain magnet constructed from manganese(III)-porphyrin and trans-dicyanobis(acetylacetonato) ruthenate(III) containing co-crystallized bulk anions and cations. AB - Two cyanide-bridged alternated 1 : 1 Ru(III)/Mn(III) complexes structurally characterized as single-chain containing co-crystallized bulk anions and cations have been successfully assembled from [Mn(TPP)(H(2)O)(2)](+) and [Ru(acac)(2)(CN)(2)](-) blocks. Systematic investigation of their magnetic properties reveals typical single-chain magnet (SCM) behaviors for both of them. PMID- 20582356 TI - Novel heteronuclear ruthenium-copper coordination compounds as efficient DNA cleaving agents. AB - The DNA-cleavage ability of novel bifunctional heterobimetallic copper-ruthenium complexes is demonstrated by using gel electrophoresis. PMID- 20582357 TI - Metal ion driven formation of a light-harvesting antenna investigated by sensitized luminescence and fluorescence anisotropy. AB - Zn(ii) complexation drives the formation of a light-harvesting antenna constituted by two multicomponent luminescent ligands: a cyclam-cored dendrimer decorated at the periphery with 16 naphthyl units and an anthracene-based molecular clip. PMID- 20582358 TI - Hydrolysis of cisplatin--a first-principles metadynamics study. AB - Cisplatin, or cis-[Pt(NH(3))(2)Cl(2)], was the first member of a new revolutionary class of anticancer drugs that is still used today for the treatment of a wide variety of cancers. The mode of action of cisplatin starts inside the cell with the hydrolysis of Pt-Cl bonds to form a Pt-aqua complex. The solvent environment plays an essential role in many biochemical processes in general, and is expected to have a particular strong effect on the activation (hydrolysis) of cisplatin and cisplatin derivatives. To investigate these solvent effects, we have studied the explicit solvent structures during cisplatin hydrolysis by means of Car-Parrinello molecular dynamics simulations. Since hydrolysis is an activated process, and thus a rare event on the simulation timescale, we have applied the metadynamics sampling technique to map out the free energy landscape from which the reaction mechanism and activation free energy are obtained. Our simulations show that hydrogen bonding between solvent water molecules and metal complexes in the hydrolyzed product systems is stronger than that in the reactant cisplatin system. In addition, the free energy profiles from our metadynamics simulations for the cisplatin hydrolysis shows that the second hydrolysis of cisplatin is thermodynamically favourable, which is in good agreement with experimental results and previous static density functional theory calculations. The reactant channels for both hydrolysis steps are rather wide and flat, indicative of a continuous spectrum of allowed mechanisms with no strong preference for either concerted dissociative or concerted associative pathways. Three or five coordinated metastable intermediates do not exist in aqueous solution. PMID- 20582359 TI - Copper protection by self-assembled monolayers of aromatic thiols in alkaline solutions. AB - Copper corrosion in alkaline solutions is inhibited by the formation of self assembled monolayers of aromatic thiols, made of either benzenethiol or 2 naphthalenethiol or 4-acetamidothiophenol. Electrochemical experiments, based on voltammetry and impedance spectroscopy, point out the much lower reactivity of copper surfaces towards oxidation, when covered by compact adlayers of the above molecules bonded through the S atom. The peculiar shape and peak position in the voltammetric reduction of residual oxides grown on modified metal surfaces suggest that they are due to Cu(I) suboxides, probably grown on reactive metal defects. XPS experiments have confirmed that the aromatic adlayers are still covering most of the Cu surface even after 1 h immersion in 0.5 M NaOH. The main changes in Auger and XP spectra indicate the formation of much less Cu(2)O in the protected samples than in the corresponding bare Cu aged in NaOH. From the experimental data the presence of defective copper oxides on modified Cu has been deduced. PMID- 20582360 TI - Structural diversity in manganese, iron and cobalt complexes of the ditopic 1,2 bis(2,2'-bipyridyl-6-yl)ethyne ligand and observation of epoxidation and catalase activity of manganese compounds. AB - A ditopic 1,2-bis(2,2'-bipyridyl-6-yl)ethyne ligand, L, has been synthesized for the first time by consecutive Suzuki and Sonogashira coupling reactions either in a one- or two-step synthesis. Coordination of L with some first-row transition metals, Fe, Mn and Co showed a very rich structural diversity that can be obtained with this ligand. Reaction of L with Mn(II)(OAc)(2) yielded a dimanganese(II) complex, [Mn(2)L(mu-OAc)(3)]PF(6), (1) where the two somewhat inequivalent trigonal-bipyramidal Mn atoms separated by 3.381 A are bridged by L and three acetate moieties. A similar reaction of L with Mn(III)(OAc)(3) yielded a very different dimanganese complex [Mn(2)L'(OH)(OAc)(2)(DMF)(2)]PF(6) x DMF (2) where L' is a E-1,2-bis(2,2'-bipyridyl-6-yl)ethene fragment that was formed in situ. The L' ligand bridges between the two Mn centers, despite its trans configuration, which leads to a very strained ethene bridging moiety. The Mn atoms are also bridged by two acetate ligands and a hydroxy group that bridges between the Mn atoms and the ethene fragment; DMF completes the octahedral coordination around each Mn atom which are separated by 3.351 A. A comproportionation reaction of L with Mn(II)(OAc)(2) and n-Bu(4)NMnO(4) yielded a tetramanganese compound, [Mn(4)(mu(3)-O)(2)(OAc)(4)(H(2)O)(2)L(2)](PF(6))(2) x 2 CH(3)CN (3). Compound 3 has a dimer of dimers structure of the tetranuclear Mn core that consists of binuclear [Mn(2)O(OAc)(2)L](+) fragment and a PF(6) anion. BVS calculations indicate that 3 is a mixed-valent 2Mn(II) plus 2Mn(III) compound where two [Mn(II)(2)O(OAc)(2)L](+) fragments are held together by Mn(III)-O inter fragment linkers which have a distorted octahedral geometry. The Mn atoms in the [Mn(2)O(OAc)(2)L](+) fragments have a capped square-pyramid configuration where an aqua ligand is capped on one of the faces. Although the aqua ligand is well within a bonding distance to a carbon atom of the proximal ethyne bridge, there does not appear to be an oxygen-carbon bond formation, rather the ligand is constrained in this position, as deduced by the observation that the bond lengths and angles of the ligand are essentially the same as those for the free ligand, L. Reaction of L with perchlorate or triflate salts of Fe(II), Mn(II) and Co(II) in dry acetonitrile yielded binuclear triple helicate structures (2:3 metal to L ratios) [Fe(2)L(3)](CF(3)SO(3))(4) x CH(3)CN (4), [Mn(2)L(3)](ClO(4))(4) x 1.7 CH(3)CN x 1.65 EtOEt (5) and [Co(2)L(3)](ClO(4))(4) x 2 CH(3)CN x 2 EtOEt (6) where each M(II) center with a slightly distorted octahedral geometry is bridged by three of the ditopic ligands. The M-M distances varied; 5.961 A (Mn), 6.233 A (Co) 6.331 A (Fe). Reaction of L with Co(ClO(4))(2) x 6 H(2)O in wet acetonitrile yielded a dicobalto(III) compound, [Co(2)L'(3)(O)(2)](ClO(4))(2) x H(2)O (7), with two types of L' fragments; one bridging between the two Co centers and two non-bridging ligands, each bonded to a Co atom via one bipyridyl group where the other is non-bonding. The octahedral coordination sphere around each Co atom is completed by the formation of a cobalt-carbon bond from the two carbon atoms of the ethene moiety of the bridging ligand and by a hydroxy moiety that is also bonded to the ethene group of the non-bridging ligand. Reaction of L with Co(ClO(4))(2) x 6 H(2)O in dry acetonitrile in the presence of Et(3)N yielded the tetracobalto(II) complex {[Co(2)L(4)(OH)(4)](ClO(4))(4)}(2) (8) with a unique twisted square configuration of cobalt ions with Co-Co distances of 3.938 to 4.131 A. In addition to the L bridging ligand the Co atoms are linked by hydroxy moieties. Some preliminary catalytic studies showed that the Mn compounds 1 and 2 were active (high yield within 3 min) for alkene epoxidation with peracetic acid and hydrogen peroxide dismutation (catalase activity). PMID- 20582361 TI - Facile access to boryltetralins and borylnaphthalenes via a cycloaddition using o quinodimethanes. AB - Borylalkenes are found to serve as efficient dienophiles in a cycloaddition reaction with o-quinodimethanes, giving diverse boryltetralins, which are convertible into borylnaphthalenes via an oxidative aromatization. PMID- 20582362 TI - Textural and mechanical characteristics of carbon aerogels synthesized by polymerization of resorcinol and formaldehyde using alkali carbonates as basification agents. AB - Five organic aerogels were prepared simultaneously by polycondensation of resorcinol and formaldehyde using different alkali carbonates (M(2)CO(3), M = Li, Na, K, Rb and Cs) as basification agents. The gelation time depended on the carbonate used, increasing from Li(2)CO(3) to Cs(2)CO(3). The porosity of the samples is defined during this process, when the three-dimensional packing of primary particles is formed. The slower the gelation, the greater the overlapping of primary particles and the formation of clusters, leading to a mechanical reinforcement of the samples and the progressive displacement of their pore size distribution (PSD) towards larger pores. Carbonization produces certain shrinkage of the structure and increases the microporosity and the Young modulus of the samples. Carbon aerogels change from mesoporous to macroporous materials as the counter-ion size of the carbonate increases. PMID- 20582363 TI - Cysteine radical cation: A distonic structure probed by gas phase IR spectroscopy. AB - The interest in the radical cations of amino acids is twofold. On the one hand, these species are relevant in enzymatic catalysis and in oxidative damage of proteins. On the other hand, as constituents of peptides and proteins, they aid the mass spectrometric characterization of these biomolecules, yielding diagnostic fragmentation patterns and providing complementary information with respect to the one obtained from even electron ions. The cysteine radical cation has been obtained by S-NO bond cleavage of protonated S-nitrosocysteine and thoroughly characterized by IRMPD spectroscopy, both in the 1000-2000 cm(-1) range (the highly structurally diagnostic, so-called 'fingerprint' range) and in the 2900-3700 cm(-1) spectral range, encompassing O-H and N-H stretching vibrations. In this way the distonic structure in which the charge is on the NH(3) group and the spin is on the sulfur atom is unambiguously demonstrated. This tautomer is a local minimum on the potential energy surface, at 29.7 kJ mol( 1) with respect to the most stable tautomer, a captodative structure allowing extensive delocalization of charge and spin. PMID- 20582364 TI - New insights into the photodynamics of acetylacetone: isomerization and fragmentation in low-temperature matrixes. AB - UV and IR photoreactivities of acetylacetone isolated at 4.3 K in four matrixes (N(2), Ne, Ar, Xe), pure and doped with O(2) are investigated, using either tunable UV and IR optical parametric oscillators, or a broad band mercury lamp. Samples are probed by UV and FTIR spectroscopies: electronic and vibrational transitions are assigned and irradiation kinetics are analyzed. Contrary to what is observed in the gas phase, stereoisomerization is the main reaction observed: UV irradiation breaks the strong H-bond of the stable enolic form of acetylacetone, leading to the observation of non-chelated forms. Isomerization among the different non-chelated forms as well as back-isomerization to the chelated form are also observed under UV irradiation. Similar reactions and reaction rates are observed for the four matrixes, indicating that the inter system crossing to the T(1) state involved in the isomerization process is very fast, probably due to efficient coupling with phonons, in contrast with gas phase where inter-system crossing is rate-limiting. When matrixes are doped with O(2), dissociation of the non-chelated forms under UV irradiation is observed and fragments, in particular CO, are formed in large amounts. Dissociation through a Norrish type-I reaction is probably one of the reaction channels occurring during electronic relaxation: dissociation is hindered by the surrounding cage in the case of pure matrixes while fragments immediately react with O(2) in the case of doped matrixes. The differences between gas phase and cold solid medium photodynamics of acetylacetone are discussed. PMID- 20582365 TI - Counteranion-dependent mechanisms of intramolecular proton transfer in aprotic solution. AB - Using the freon mixture CDF(3)/CDClF(2) as solvent we have been able to measure the (1)H and (15)N NMR spectra of the doubly (15)N labeled 2,2'-bipyridinium cation (BpyH(+)) at temperatures down to 115 K. The obtained NMR parameters strongly depend on the type of counteranions indicating the formation of ion pairs. In the case of the bulky poorly coordinating tetrakis[3,5 bis(trifluoromethyl)phenyl]-borate as the counteranion a strong intramolecular NHN hydrogen bond was observed in BpyH(+) exhibiting a degenerate intramolecular proton transfer which is of the order of 10(6) s(-1) even at 120 K. By contrast, the weak hydrogen bond acceptor tetrafluoroborate favors a weak intermolecular FHN interaction and quenches the intramolecular proton transfer. The intramolecular proton transfer requires in this case a dissociation of the ion pair which is hindered by the Coulomb interaction. A slow intramolecular proton transfer was observed in the case of dichloroacetate which forms a strong intermolecular OHN hydrogen bond to BpyH(+). The mechanism of this transfer presumably involves a preliminary intermolecular proton transfer from nitrogen towards oxygen followed by a hydrogen bond switch to the neighboring nitrogen to which the proton is then transferred. PMID- 20582366 TI - Single nanocavity electrodes: fabrication, electrochemical and photonic properties. AB - Nanosphere lithography has been used to create spherical recessed electrodes of nanometre dimensions capable of enhancing fluorescent signals. PMID- 20582367 TI - Raman and SERS spectroscopy of cucurbit[n]urils. AB - Cucurbit[n]urils (CB[n]) are a family of supramolecular hosts which can provide highly selective recognition based on their size (n). In this work we study their Raman spectroscopic signatures both experimentally and by molecular simulation and find systematic trends providing evidence of ring strain effects with size. Furthermore, we present for the first time their surface-enhanced Raman scattering (SERS) spectra utilizing both nanostructured surface and nanoparticle based approaches. Using SERS we can detect CB[n] at the ppb level and are able to distinguish between them in mixtures. Our study paves the way for utilization of CB[n] in highly sensitive, multiplexed, real time and high throughput molecular recognition assays based on SERS. PMID- 20582368 TI - Coupling between motor proteins determines dynamic behaviors of motor protein assemblies. AB - Transport of intracellular cargos by multiple microtubule motor proteins is believed to be a common and significant phenomenon in vivo, yet signatures of the microscopic dynamics of multiple motor systems are only now beginning to be resolved. Understanding these mechanisms largely depends on determining how grouping motors affect their association with microtubules and stepping rates, and hence, cargo run lengths and velocities. We examined this problem using a discrete state transition rate model of collective transport. This model accounts for the structural and mechanical properties in binding/unbinding and stepping transitions between distinct microtubule-bound configurations of a multiple motor system. In agreement with previous experiments that examine the dynamics of two coupled kinesin-1 motors, the energetic costs associated with deformations of mechanical linkages within a multiple motor assembly are found to reduce the system's overall microtubule affinity, producing attenuated mean cargo run lengths compared to cases where motors are assumed to function independently. With our present treatment, this attenuation largely stems from reductions in the microtubule binding rate and occurs even when mechanical coupling between motors is weak. Thus, our model suggests that, at least for a variety of kinesin dependent transport processes, the net 'gains' obtained by grouping motors together may be smaller than previously expected. PMID- 20582369 TI - Bis(phosphinimino)methanides as non-innocent ligand in zinc chemistry: synthesis and structures. AB - Reactions of the bis(phosphinimino)methane {CH2(Ph2PNSiMe3)2} with the zinc dihalides ZnCl2 and ZnI2 afforded the corresponding bis(phosphinimino)methane complexes [{(Me3SiNPPh2)2CH2}ZnCl2] (1) and [{(Me3SiNPPh2)2CH2}ZnI2] (2). In contrast, treatment of {CH2(Ph2PNSiMe3)2} with ZnPh2 in toluene gave the bis(phosphinimino)methanide complex of [{(Me3SiNPPh2)2CH}ZnPh] (3). Further reaction of 3 with the heterocumulenes di(p-tolyl)carbodiimine and diphenyl ketene resulted via a nucleophilic addition of the methine carbon atom of the {CH(Ph2PNSiMe3)2}- ligand to the heterocumulenes in a C-C bond formation. New tripodal phenyl zinc complexes of composition [{(Me3SiNPPh2)2CH)(p-Tol)NC-N(p Tol)}ZnPh] (4) and [{(Me3SiNPPh2)2CH)(Ph2CC-O)}ZnPh] (5) were obtained. PMID- 20582370 TI - Environmental geochemistry reflected by rare earth elements in Bohai Bay (North China) core sediments. AB - In Bohai Bay sediment, two cores were collected to estimate the source of sediments, and assess the environmental changes. Sequential extractions were carried out in this study. Rare earth elements (REE) were leached out from four labile fractions: Exchangeable (L1), Bound to carbonates (L2), Bound to Fe-Mn oxides (L3), Bound to organic matter (L4), and the remainder was Residual (R5). The percentages of REE in different fractions follow the order: R5 > L3 > L2 > L4 > L1. With heavy REE depletion and no pronounced REE fractionation, NASC normalized REE patterns of Bohai Bay sediments are quite consistent with that of Haihe River sediment, which is the key river of Bohai Bay. Y/Ho ratios of total contents are all much lower than the average value of continental crust, while Y/Ho ratios of L2 are higher than those of other fractions. Based on the patterns of REE and Y/Ho ratios of samples, sediments of Bohai Bay mainly come from terrigenous matters, which are mainly brought by Haihe River. And REE combined with carbonates may be partly inherited from anthropogenic matter. Moreover, environmental changes exert significant influences on the patterns and fractionations of REE, and they can be deduced from the characteristics of REE. Our results on the patterns and burial fluxes of REE reflect two environmental changes: Bohai Bay has been shifting towards more reducing conditions in the last one hundred years, and there was a large flood in 1939. PMID- 20582371 TI - Torsional energy levels of nitric acid in reduced and full dimensionality with ElVibRot and Tnum. AB - The internal rotation (nu(9)) of nitric acid is studied using several ab initio models including 1D models and full dimensionality (9D) ones. For the 9D calculations, an adiabatic separation between the large amplitude motion, i.e. the torsion, and the eight other modes is performed. The potential energy surface is calculated at CCSD(T) level with a triple zeta atomic basis set and is expanded in a Taylor series up to the second-order along the torsional path. The vibrational calculations are performed with the codes ElVibRot and Tnum. Our main results show that the torsional energy levels and the corresponding tunneling spliting are in good agreement with the experimental ones. Furthermore, the resonance between 2nu(9) and nu(5) (NO(2) in-plane bending) is also well described with full dimensionality models. PMID- 20582372 TI - Chitosan as efficient porous support for dispersion of highly active gold nanoparticles: design of hybrid catalyst for carbon-carbon bond formation. AB - Macroporous catalyst was obtained by dispersing nanosized gold in the fibrils of the chitosan matrix, followed by CO(2) supercritical drying of the resulting hybrid material. The accessible gold nanoparticles are highly active for carbon carbon cross coupling reactions. PMID- 20582373 TI - Nickel-catalyzed, sodium iodide-promoted reductive dimerization of alkyl halides, alkyl pseudohalides, and allylic acetates. AB - The first general method for the reductive dimerization of alkyl halides, alkyl mesylates, alkyl trifluoroacetates, and allylic acetates is reported which proceeds with low catalyst loading (0.5 to 5 mol%), generally high yields (80% ave yield), and good functional-group tolerance. PMID- 20582374 TI - Prediction of the structures of free and oxide-supported nanoparticles by means of atomistic approaches: the benchmark case of nickel clusters. AB - The structures of Ni/MgO nanoparticles are studied by means of global optimization searches. The results from four different model potentials, sharing the same functional forms but different parametrizations, are reported and compared. Two parametrizations over four give qualitatively correct results, and one of them is also quantitatively satisfactory. The other models fail to explain some qualitative features observed in the experiments, such as the formation of hcp nanodots at small sizes or the transition to fcc structures at large sizes. The important features that an atomistic potential must present for the correct prediction of Ni cluster structures are discussed and generalized. PMID- 20582375 TI - The first members of the octasubstituted naphthalene spider-host series with type I (abababab) conformation: gateway to new nano-host gas storage materials. AB - Octakis(m-tolyloxymethyl)naphthalene, the first Type I spider host produced, crystallises from tetraglyme forming a novel channel structure with the host molecule attaining exact D(2) symmetry. The (flexible) channel structure is retained for guest CS(2), the host now only having exact C(2) symmetry. The octa sulfone octakis(m-tolylsulfonylmethyl)naphthalene is also of Type I in its triclinic DMSO clathrate. DNMR establishes a substantial difference in molecular flexibilities in solution. PMID- 20582376 TI - Enzymatic formation of a photoresponsive supramolecular hydrogel. AB - This paper reports the first example of the use of an enzymatic reaction to generate a photoresponsive hydrogelator, which represents a convenient route to expand the scope of optically controlled molecular self-assembly in water. PMID- 20582377 TI - Organic dyes with remarkably high absorptivity; all solid-state dye sensitized solar cell and role of fluorine substitution. AB - A series of new organic D-pi-A dyes, A1, A2-H and A2-F, possessing a remarkably high absorption extinction coefficient of epsilon > 5.0 x 10(4) M(-1) cm(-1) at peak wavelength were synthesized, among which, A2-F having a key fluorine substitution attains excellent all solid-state DSSC performance, with optimized parameters of eta = 4.86%, J(SC) = 7.52 mA cm(-2), V(OC) = 0.91 V, and FF = 0.71. PMID- 20582378 TI - The interface of chemical biology and the nervous system (related to the NIDA Chemical Genomics Symposium). PMID- 20582379 TI - Band-gap tunable (Cu2Sn)(x/3)Zn(1-x)S nanoparticles for solar cells. AB - Sphalerite-type (Cu(2)Sn)(x/3)Zn(1-x)S (0 < or = x < or = 0.75) nanocrystals with tunable band gaps were successfully prepared via a solvothermal approach. Band gaps of the nanoparticles could be adjusted from 3.48 eV to 1.23 eV by changing the composition. Their implementation in quantum dot sensitized solar cells (QDSSCs) suggests considerable potential in solar cells. PMID- 20582380 TI - Silver triflate-catalyzed three-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and alpha,beta-unsaturated carbonyl compound. AB - A highly efficient silver triflate-catalyzed three-component reaction of 2 alkynylbenzaldehyde, sulfonohydrazide, and alpha,beta-unsaturated carbonyl compound is reported, which affords H-pyrazolo[5,1-a]isoquinoline-1-carboxylates in good yield. PMID- 20582382 TI - Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G quadruplex binding motif. AB - A bis-guanylhydrazone derivative of diimidazo[1,2-a:1,2-c]pyrimidine has unexpectedly been found to be a potent stabiliser of several quadruplex DNAs, whereas there is no significant interaction with duplex DNA. Molecular modeling suggests that the guanylhydrazone groups play an active role in quadruplex binding. PMID- 20582381 TI - Synthesis and evaluation of indazole based analog sensitive Akt inhibitors. AB - The kinase Akt is a key signaling node in regulating cellular growth and survival. It is implicated in cancer by mutation and its role in the downstream transmission of aberrant PI3K signaling. For these reasons, Akt has become an increasingly important target of drug development efforts and several inhibitors are now reaching clinical trials. Paradoxically it has been observed that active site kinase inhibitors of Akt lead to hyperphosphorylation of Akt itself. To investigate this phenomenon we here describe the application of a chemical genetics strategy that replaces native Akt with a mutant version containing an active site substitution that allows for the binding of an engineered inhibitor. This analog sensitive strategy allows for the selective inhibition of a single kinase. In order to create the inhibitor selective for the analog sensitive kinase, a diversity of synthetic approaches was required, finally resulting in the compound PrINZ, a 7-substituted version of the Abbott Labs Akt inhibitor A 443654. PMID- 20582383 TI - Assessment of pain expression in infant cry signals using empirical mode decomposition. AB - BACKGROUND: The presence of decoupling, i.e. the absence of coupling between fundamental frequency variation and intensity contour during phonetic crying, and its extent, reflects the degree of maturation of the central nervous system. OBJECTIVES: The aim of this work was to evaluate whether Empirical Mode Decomposition (EMD) is a suitable technique for analyzing infant cries. We hereby wanted to assess the existence and extent of decoupling in term neonates and whether an association between decoupling (derived from EMD) and clinical pain expression could be unveiled. METHODS: To assess decoupling in healthy term neonates during procedural pain, 24 newborns were videotaped and crying was recorded during venous blood sampling. Besides acoustic analysis, pain expression was quantified based on the Modified Behavioral Pain Scale (MBPS). Fundamental frequency and the intensity contour of the cry signals were extracted by applying the EMD to the data, and the correlation between the two was studied. RESULTS: Based on data collected in healthy term neonates, correlation coefficients varied between 0.39 and 0.83. The degree of decoupling displayed extended variability between the neonates and also in different cry bouts in a crying sequence within an individual neonate. CONCLUSION: When considering the individual ratio between the mean correlation of cry bouts during a crying sequence and their standard deviation, there seems to be a positive trend with increasing MBPS value. This might indicate that higher stressed subjects have less consistency in the investigated acoustic cry features, concluding that EMD has potential in the assessment of infant cry analysis. PMID- 20582384 TI - Construction of an interface terminology on SNOMED CT. Generic approach and its application in intensive care. AB - OBJECTIVE: To provide a generic approach for developing a domain-specific interface terminology on SNOMED CT and to apply this approach to the domain of intensive care. METHODS: The process of developing an interface terminology on SNOMED CT can be regarded as six sequential phases: domain analysis, mapping from the domain concepts to SNOMED CT concepts, creating the SNOMED CT subset guided by the mapping, extending the subset with non-covered concepts, constraining the subset by removing irrelevant content, and deploying the subset in a terminology server. RESULTS: The APACHE IV classification, a standard in the intensive care with 445 diagnostic categories, served as the starting point for designing the interface terminology. The majority (89.2%) of the diagnostic categories from APACHE IV could be mapped to SNOMED CT concepts and for the remaining concepts a partial match was identified. The resulting initial set of mapped concepts consisted of 404 SNOMED CT concepts. This set could be extended to 83,125 concepts if all taxonomic children of these concepts were included. Also including all concepts that are referred to in the definition of other concepts lead to a subset of 233,782 concepts. An evaluation of the interface terminology should reveal what level of detail in the subset is suitable for the intensive care domain and whether parts need further constraining. In the final phase, the interface terminology is implemented in the intensive care in a locally developed terminology server to collect the reasons for intensive care admission. CONCLUSIONS: We provide a structure for the process of identifying a domain specific interface terminology on SNOMED CT. We use this approach to design an interface terminology on SNOMED CT for the intensive care domain. This work is of value for other researchers who intend to build a domain-specific interface terminology on SNOMED CT. PMID- 20582385 TI - Detection algorithm for single motor unit firing in surface EMG of the trapezius muscle. AB - BACKGROUND: Work-related musculoskeletal disorders (MSD) of the neck and the shoulders are a growing problem in society. An interesting pattern of spontaneous muscle activity, the firing of a single motor unit, in the trapezius muscle is observed during a laboratory study in a rest state or a state with a mental load. OBJECTIVE: In this study, we report on the finding of the single motor unit firing and we present a detection algorithm to localize these single motor unit firings. METHODS: A spike train detection algorithm, using a nonlinear energy operator and correlation, is presented to detect burst of highly correlated, high energetic spike-like segments. RESULTS: This single motor unit was visible in 65% of the test subjects on one or both trapezius muscles although there was no change in posture of the test subjects. All the segments in the data that were determined as single motor unit firings were detected by the algorithm. DISCUSSION: The physiological meaning of this firing pattern is a very low and subconscious contraction of the muscle. A long-term contraction could lead to the exhaustion of the muscle fibers, thus resulting in musculoskeletal disorders. The detection algorithm is able to localize this phenomenon in a sEMG measurement. The ability of detecting these firings is helpful in the research of its origin. CONCLUSION: The detection algorithm can be used to gain insight in the physiological origin of this phenomenon. In addition, the algorithm can also be used in a biofeedback system to warn the user for this undesired contraction to prevent MSD. PMID- 20582386 TI - Interferences between baroreflex and respiration. Evaluation by symbolic analysis and conditional entropy. AB - BACKGROUND: The baroreflex is one of the most important short-term cardiovascular autonomic control mechanisms. Its interactions with other reflexes, mainly cardiopulmonary reflexes, are of paramount importance in controlling heart rate. OBJECTIVES: This study assesses the coupling between baroreflex and respiration during a progressive bicycle mild dynamical exercise. METHODS: The coupling was assessed by symbolic analysis and conditional entropy. RESULTS: Findings suggested the close relationship between the baroreflex sequences and the phase of respiratory signal and, thus, the interference between baroreflex and cardiopulmonary reflexes. CONCLUSIONS: Indexes describing baroreflex based on spontaneous variability are strongly affected by cardiopulmonary influences. PMID- 20582387 TI - Linear and fractal heart rate dynamics during sleep at high altitude. Investigation with textile technology. AB - OBJECTIVES: To investigate the effects of hypoxia during sleep on linear and self similar components of heart rate variability (HRV) in eight healthy subjects at high altitude on Mount Everest. METHODS: ECG was monitored by using an innovative textile-based device, the MagIC system. For each subject three night recordings were performed at sea level (SL), at 3500 m and 5400 m above SL. RR Interval (RRI) was derived on a beat-by-beat basis from the ECG and the VLF, LF and HF spectral components and the LF/HF ratio were estimated. Short- (alpha1) and long term (alpha2) scale exponents as well as the recently proposed spectrum of self similarity coefficients, alpha(n) were estimated by detrended fluctuation analysis (DFA). RESULTS: With respect to SL, all HRV parameters but one (alpha2) were significantly modified at 3500 m. However, at 5400 m they tended to return to the SL values and this was in contrast with the increase in the hypobaric hypoxia and in the number of central sleep apneas occurring at higher altitude. The only HRV index that displayed changes at 5400 m was the DFA alpha(n) spectrum, with alpha(n) values significantly lower than at SL for 20 < n <50 and higher for 200 < n <400, being n the box size. CONCLUSIONS: While the biological interpretation of these results is still in progress, our data indicates that the cardiac response to high altitude hypoxia during sleep can hardly be fully explored by traditional HRV estimators only, and requires the additional support of more sophisticated indexes exploring also nonlinear and fractal features of cardiac variability. PMID- 20582388 TI - A virtual reality simulator for teaching and evaluating dental procedures. AB - OBJECTIVES: We present a dental training system with a haptic interface that allows dental students or experts to practice dental procedures in a virtual environment. The simulator is able to monitor and classify the performance of an operator into novice or expert categories. The intelligent training module allows a student to simultaneously and proactively follow the correct dental procedures demonstrated by an intelligent tutor. METHODS: The virtual reality (VR) simulator simulates the tooth preparation procedure both graphically and haptically, using a video display and haptic device. We evaluated the performance of users using hidden Markov models (HMMs) incorporating various data collected by the simulator. We implemented an intelligent training module which is able to record and replay the procedure that was performed by an expert and allows students to follow the correct steps and apply force proactively by themselves while reproducing the procedure. RESULTS: We find that the level of graphics and haptics fidelity is acceptable as evaluated by dentists. The accuracy of the objective performance assessment using HMMs is encouraging with 100 percent accuracy. CONCLUSIONS: The simulator can simulate realistic tooth surface exploration and cutting. The accuracy of automatic performance assessment system using HMMs is also acceptable on relatively small data sets. The intelligent training allows skill transfer in a proactive manner which is an advantage over the passive method in a traditional training. We will soon conduct experiments with more participants and implement a variety of training strategies. PMID- 20582390 TI - [Tako-Tsubo cardiomyopathy--what do, what don't we know?]. PMID- 20582389 TI - [Patient care in the acute phase of stress induced cardiomyopathy (Tako-Tsubo cardiomyopathy)--and thereafter?]. AB - The prognosis of patients presenting with Tako-Tsubo cardiomyopathy (TTC) is generally considered to be favorable. However, in the acute phase of the disorder complications are not infrequent and, therefore, continuous monitoring and consistent therapy in an intensive care unit is essential. Typical complications in patients with TTC are cardiogenic shock, obstruction of the left ventricular outflow tract (LVOT), occasionally accompanied by acute mitral regurgitation, arrhythmias, predominantly torsade de pointes tachycardias due to QT prolongation, left ventricular (LV) thrombus formation with or without consecutive thromboembolic events, and LV rupture. After confirmation of TTC by coronary angiography, repeat echocardiography should be performed. A standardized therapy for patients with TTC has so far not been established. Recommendations for the acute phase include the administration of anxiolytic agents for patients who present with preceding emotional stress, consistent therapy of physical stressors (such as pain or asthma) and avoidance of catecholamine therapy. Shock due to LVOT obstruction is treated by administration of volume and beta-blockers. With respect to the occurrence of torsade de pointes tachycardias, drugs which might cause QT prolongation should not be given. The notable incidence of LV thrombus formation justifies therapeutic anticoagulation. Systematic studies and treatment recommendations for the prophylaxis of recurrent TTC do not exist. The recently reported association between TTC and malignant disorders should prompt tumor screening and subsequent preventive medical checkups in patients affected by TTC. PMID- 20582391 TI - Proposed Mayo Clinic criteria for the diagnosis of Tako-Tsubo cardiomyopathy and long-term prognosis. AB - Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy with a clinical presentation indistinguishable from myocardial infarction. TTC is estimated to represent 1%-2% of patients presenting with acute myocardial infarction. It most commonly occurs in postmenopausal women and is frequently precipitated by a stressful event. Chest pain and dyspnea are the typical presenting symptoms. Transient ST-segment elevation on ECG and a small rise in cardiac biomarkers are common. Characteristic wall motion abnormalities extend beyond the territory of a single epicardial coronary artery in the absence of obstructive coronary lesions. Supportive treatment leads to spontaneous rapid recovery in nearly all patients. The prognosis is excellent, and recurrence occurs in < 10% of patients. In this article, we review the clinical features of TTC that form the basis of the Mayo Clinic diagnostic criteria, as well as the long-term prognosis for this type of cardiomyopathy. PMID- 20582392 TI - Combined-modality treatment for anal cancer: current strategies and future directions. AB - BACKGROUND: Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C (MMC) is the treatment of choice for anal carcinoma. The most appropriate radiation (RT) dose, fractionation, techniques, and the most effective chemotherapy regimen (agents, number of neoadjuvant, concomitant, adjuvant cycles) remain to be established. MATERIAL AND METHODS: This review article focuses on recent randomized trials designed to improve standard 5-FU/MMC based CRT through the inclusion of (induction, concurrent, maintenance) cisplatin, and describes developments in combining RT with other chemotherapeutic drugs and targeted therapies. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. RESULTS: Based on results of three recent randomized phase III trials, neither induction chemotherapy (RTOG 98-11, ACCORD 03) or maintenance chemotherapy with 5-FU/cisplatin (ACT II) nor RT dose escalation (ACCORD 03) improved the outcome of concurrent 5-FU/MMC-CRT. A randomized phase II trial (EORTC 22011-40014) compared concurrent 5-FU/MMC-CRT with cisplatin/ MMC CRT. The response rate of cisplatin/MMC-CRT was promising, but compliance to this regimen was limited. Current phase I/II studies are evaluating the use of capecitabine, oxalipatin, and the EGFR (epidermal growth factor receptor) inhibitor cetuximab. CONCLUSION: Concurrent 5-FU/MMC-CRT without induction or maintenance chemotherapy remains the standard of care for anal cancer patients. PMID- 20582393 TI - Long-term outcome of mitomycin C- and 5-FU-based primary radiochemotherapy for esophageal cancer. AB - BACKGROUND AND PURPOSE: For definitive radiochemotherapy, 5 fluorouracil/cisplatin protocols have been considered the standard of care for esophageal carcinoma over the last 2 decades. By contrast, most patients treated at the University Hospital, LMU Munich, Germany, received 5 fluorouracil/mitomycin C. The objective of this retrospective analysis was to determine the value of 5-fluorouracil/mitomycin-C-based therapy. PATIENTS AND METHODS: Tumor stage, treatment received, and outcome data of patients treated for esophageal cancer between 1982 and 2007 were collected; endpoint of the analysis was overall survival. RESULTS: 298 patients with inoperable cancer of the esophagus were identified (16.8% adenocarcinoma, 77.5% squamous cell carcinoma). At diagnosis, 61.7% (184/298) had UICC stage III-IV, 54.4% (162/298) positive lymph nodes, and 26.5% (79/298) metastatic disease. 74.5% of all patients (222/298) received radiation doses between 55 and 65 Gy, 65.8% (196/298) were subjected to concomitant chemotherapy. The median follow-up period (patients alive) was 4.1 years. A significant increase of overall survival (p < 0.0001) in the radiochemotherapy versus the radiotherapy-alone group was observed. 52% (102/196) in the 5-fluorouracil/ mitomycin C group had tumor stages comparable to the RTOG 85-01 study cohort (T1-3 N0-1 M0). The median survival in this subgroup was 18.2 months, 3- and 5-year survival rates were 22.7% (21/102) and 15.0% (13/102), respectively. CONCLUSION: Despite being nominally inferior to platinum based radiochemotherapy, the overall survival rates are in a similar range. Thus, the mitomycin-C-based radiochemotherapy approach may considered to be as effective as the standard therapy. However, there is no randomized trial available in order to prove the equality. PMID- 20582394 TI - Volumetric modulated arc therapy for advanced pancreatic cancer. AB - BACKGROUND: Intensity-modulated radiotherapy (IMRT) allows for improved sparing of organs at risk (OARs) in advanced pancreatic cancer. A planning study evaluated if volumetric modulated arc therapy (RapidArc [RA]) could be used as an alternative to IMRT in such cases. PATIENTS AND METHODS: In ten patients, five field IMRT (5f-IMRT) plans with fixed gantry positions were compared to RA plans using similar constraints for planning target volume (PTV) and OARs. PTV coverage, conformity indices (CI), and OAR doses were compared. One patient was treated using RA and calculated dose distributions were measured in coronal planes in a solid-water phantom. RESULTS: RA plans showed superior mean CI of 1.09 +/- 0.02 (+/- 1 SD [standard deviation]) versus 1.20 +/- 0.10 in 5f-IMRT (p = 0.003). Both techniques achieved similar sparing of the right kidney, but RA significantly reduced left kidney doses with V(15) of 7.2% +/- 5.3% and 15.9% +/- 11.1%, respectively; p = 0.02. RA modestly decreased mean doses to liver (13.8 vs. 15.1 Gy; p = 0.003), stomach (16.7 vs. 17.9 Gy; p = 0.017), small bowel (19.8 vs. 22.1 Gy; p < 0.001), and duodenum (38.8 vs. 41.9 Gy; p = 0.004). Film dosimetry revealed excellent agreement between calculated and measured dose distributions. The delivery time for RA was < 3 min. CONCLUSION: RA planning achieved superior CI for pancreatic tumors compared to 5f-IMRT, and modestly reduced OAR doses. Fast treatment delivery using RA may decrease the risk of intrafractional organ motion. PMID- 20582395 TI - [Automated delivery of codes for charge in radiotherapy]. AB - BACKGROUND AND PURPOSE: For the medical billing of Radiotherapy every fraction has to be encoded, including date and time of all administered treatments. With fractions averaging 30 per patient and about 2,500 new patients every year the number of Radiotherapy codes reaches an amount of 70,000 and more. Therefore, an automated proceeding for transferring and processing therapy codes has been developed at the Department of Radiotherapy Freiburg, Germany. This is a joint project of the Department of Radiotherapy, the Administration Department, and the Central IT Department of the University Hospital of Freiburg. MATERIAL AND METHODS: The project consists of several modules whose collaboration makes the projected automated transfer of treatment codes possible. The first step is to extract the data from the department's Clinical Information System (MOSAIQ). These data are transmitted to the Central IT Department via an HL7 interface, where a check for corresponding hospitalization data is performed. In the further processing of the data, a matching table plays an important role allowing the transformation of a treatment code into a valid medical billing code. In a last step, the data are transferred to the medical billing system. RESULTS AND CONCLUSION: After assembling and implementing the particular modules successfully, a first beta test was launched. In order to test the modules separately as well as the interaction of the components, extensive tests were performed during March 2006. Soon it became clear that the tested procedure worked efficiently and accurately. In April 2006, a pilot project with a few qualities of treatment (e.g., computed tomography, simulation) was put into practice. Since October 2006, nearly all Radiation Therapy codes (approximately 75,000) are being transferred to the comprehensive Hospital Information System (HIS) automatically in a daily routine. PMID- 20582396 TI - Dosimetric evaluation of high-dose-rate interstitial brachytherapy boost treatments for localized prostate cancer. AB - PURPOSE: To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. MATERIAL AND METHODS: Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters. RESULTS: The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23. CONCLUSION: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended. PMID- 20582397 TI - [Is retrospective preventive detention finished? Legal consequences of the verdict of the European Court of Human Rights from 17.12.2009]. AB - On 17.12.2009 the European Court of Human Rights announced a verdict on the admissibility of retrospective abolition of the 10-year time limit for the first preventive detention for violent criminals after a court process lasting 5.5 years. The Court decreed that this was a breach of the Convention and awarded the internee damages of 50,000 EUR. This verdict, which has initially brought the damages to the person concerned but not freedom, will have substantial effects on the right of preventive detention. This decision is final since 10 May 2010 after the High Court rejected the appeal of the Federal Government. This article presents the verdict of the European Court and discusses the sequelae for the right of preventive detention. PMID- 20582398 TI - Triple jeopardy: impact of partner violence perpetration, mental health and substance use on perceived unmet need for mental health care among men. AB - OBJECTIVES: To examine the relationship between intimate partner violence (IPV) perpetration, serious mental illness, and substance use and perceived unmet need for mental health treatment in the past year among men in the general population using the behavioral model for health-care use (Aday and Anderson in Health Serv Res 9:208-220, 1974; Andersen in A behavioral model of families' use of health services, 1968; Andersen in Med Care 46:647-653, 2008). METHODS: Non-Hispanic black, Hispanic, and non-Hispanic white males aged 18-49 years and cohabiting with a spouse/partner were included in this analysis of the 2002 National Survey on Drug Use and Health. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated using logistic regression. RESULTS: The proportion of men reporting unmet treatment need was greater among IPV perpetrators than nonperpetrators (12.1 vs. 3.4%, respectively). Hazardous drinking, illicit drug use, alcohol and drug abuse/dependence, and SMI were also more common among perpetrators. Perpetrators were twice as likely to report unmet need for treatment after taking predisposing, enabling, and need factors into account (AOR 2.00, CI 1.13-3.55). Alcohol abuse/dependence (AOR 2.96, CI 1.79-4.90), drug abuse/dependence (AOR, 1.79, CI 1.01-3.17), substance abuse treatment (AOR 3.09, CI 1.18-8.09), and SMI (AOR 8.46, CI 5.53-12.94) were independently associated with perceived unmet need for treatment. CONCLUSIONS: These findings suggest that men who perpetrate IPV are at increased risk of perceived unmet need for mental health care. This study also emphasizes the need to identify substance use disorders and mental health problems among IPV perpetrators identified in health, social service, or criminal justice settings. Further research should address barriers to care specific to men who perpetrate IPV beyond economic factors. PMID- 20582399 TI - Measuring smoking-related preoccupation and compulsive drive: evaluation of the obsessive compulsive smoking scale. AB - RATIONALE: Tobacco use for many people is compulsive in nature. Compelling theories of how smoking becomes compulsive exist but are largely based on extrapolation from neuroscience findings. Research on smokers is impeded, in part, by a lack of instruments that specifically measure compulsive smoking. OBJECTIVE: This study evaluated the measurement structure and validity of the Obsessive Compulsive Smoking Scale (OCSS), a ten-item questionnaire designed to measure compulsive smoking. METHODS: Participants were 239 daily smokers (>/=1 cigarette/day), including 142 students at a public university in Chicago and 97 veterans treated at the VA Boston Healthcare System. The OCSS and questionnaires measuring current and past smoking, cigarette craving, automatic smoking, and nicotine dependence were administered. RESULTS: Factor analysis with maximum likelihood extraction and oblique rotation revealed two correlated underlying factors, interpreted as "Preoccupation with Smoking" and "Compulsive Drive." The measurement structure was consistent across students and veterans, and confirmed in an independent sample of adults (n = 95). Veterans exhibited higher OCSS scores (full scale and subscales) than students. Across groups, higher OCSS scores were positively correlated with smoking intensity, craving, and nicotine dependence. OCSS full-scale and compulsive drive scores, but not smoking preoccupation scores, were inversely correlated with past month smoking reduction and minutes since last cigarette. CONCLUSIONS: The OCSS is a valid and reliable inventory for measuring the degree to which daily smokers are preoccupied with smoking and engage in compulsive tobacco use, and may be useful for advancing understanding of core smoking phenotypes or for tailoring cessation therapies. PMID- 20582400 TI - Part II: defining and quantifying individual and co-cultured intracellular proteomes of two thermophilic microorganisms by GeLC-MS2 and spectral counting. AB - Probing the intracellular proteome of Thermotoga maritima and Caldicellulosiruptor saccharolyticus in pure and co-culture affords a global investigation into the machinery and mechanisms enduring inside the bacterial thermophilic cell at the time of harvest. The second of a two part study, employing GeLC-MS(2) a variety of proteins were confidently identified with <1% false discovery rate, and spectral counts for label-free relative quantification afforded indication of the dynamic proteome as a function of environmental stimuli. Almost 25% of the T. maritima proteome and 10% of the C. saccharolyticus proteome were identified. Through comparison of growth temperatures for T. maritima, a protein associated with chemotaxis was uniquely present in the sample cultivated at the non-optimal growth temperature. It is suspected that movement was induced due to the non-optimal condition as the organism may need to migrate in the culture to locate more nutrients. The inventory of C. saccharolyticus proteins identified in these studies and attributed to spectral counting, demonstrated that two CRISPR-associated proteins had increased expression in the pure culture versus the co-culture. Further focusing on this relationship, a C. saccharolyticus phage-shock protein was identified in the co-culture expanding a scenario that the co-culture had decreased antiviral resistance and accordingly an infection-related protein was present. Alterations in growth conditions of these bacterial thermophilic microorganisms offer a glimpse into the intricacy of microbial behavior and interaction. PMID- 20582401 TI - A fast method for screening and/or quantitation of tetrahydrocannabinol and metabolites in urine by automated SPE/LC/MS/MS. AB - Marijuana is one of the most commonly used illicit substances. The high usage of this substance results in it being commonly encountered in clinical samples throughout the USA and Europe. Due to its wide availability and use, marijuana is also commonly encountered in forensic toxicology laboratories. The proposed method utilized an automated solid phase extraction (SPE) coupled to liquid chromatography/mass spectrometry (LC/MS). The automated SPE procedure was developed using Hysphere C8-EC sorbent, and the high performance liquid chromatography (HPLC) separation was performed using an Xterra MS C(18) column with a total runtime of 10 min. The standard curves linearity generally fell between 6 and 500 ng/mL. The limits of detection ranged from 2 to 4 ng/mL, and the limits of quantitation ranged from 8 to 12 ng/mL. The bias and imprecision were determined using a simple analysis of variance (single factor). The results demonstrate bias as <11% and percent imprecision as <12% for all components at four quality control levels. This method has been in use for over 2 years and has been applied to numerous forensic samples. When compared to other published methods, it exceeds others in its simplicity and speed of analysis. This method takes advantage of robotics and automation for a total analysis time of 10 min, including sample preparation, separation, and detection. PMID- 20582402 TI - Determination of organic acids in Vaccinium berry standard reference materials. AB - Nine organic acids (citric acid, galacturonic acid, glycolic acid, isocitric acid, malic acid, oxalic acid, quinic acid, shikimic acid, and tartaric acid) and two anions (phosphate and sulfate) were determined in a suite of Vaccinium berry containing dietary supplement standard reference materials (SRMs). Following solvent extraction, three independent methods were utilized in the quantification of these compounds. The first method involved reversed-phase liquid chromatography with ultraviolet absorbance detection at 210 nm and isotope dilution mass spectrometry. The second method utilized ion chromatography with conductivity detection. Finally, gas chromatography with isotope dilution mass spectrometry detection was used following derivatization with N-methyl-N trifluoroacetamide (MSTFA). The combined data from these methods was used for the assignment of organic acid levels in the seven candidate SRMs. PMID- 20582403 TI - Quality analytics of Internet pharmaceuticals. AB - Trading pharmaceutical products through the Internet poses several challenges related to legal responsibilities, good distribution practices, information content and patient use, financial implications, but also regarding product quality. One of the major concerns is the well-known phenomenon of counterfeited and/or substandard drugs commercialized through rogue Internet sites. Therefore, controlling and assuring the quality of those products has become an important and challenging task for the authorities. This review gives an overview of the different quality attributes that can be evaluated to have a complete understanding of the quality of the finished pharmaceutical product traded through the Internet, as well as the current analytical techniques that serve this objective. Aspects considered are labelling and packaging, physicochemical quality attributes, identification and assay of active substances and/or excipients, impurity profiling, biopharmaceutical testing and data interpretation. PMID- 20582404 TI - Spectroscopic and analytical characteristics of an inductively coupled argon plasma combined with hydride generation with or without simultaneous introduction of the sample aerosol for optical emission spectrometry. AB - A radially viewed inductively coupled argon plasma was used for optical emission spectrometry of volatile species formed by reaction with NaBH(4) (hydride generation). The volatile hydrides were either introduced into the plasma alone or at the same time as a sample aerosol generated by pneumatic nebulization with a commercially available Concomitant Metals Analyzer. The effects of the forward power, the presence of pre-reducing agents [(NH(2))(2)SC, KI, KBr and hot HCl], the occurrence of easily ionized elements (Ca, K, Mg and Na) in the analyte solutions on the excitation temperature (as measured via Ar atomic lines) and the electron number density were investigated for both of the sample introduction modes applied. The detection limits and the signal-to-background intensity ratios for As, Bi, Sb, Se and Sn lines were also evaluated and were observed to deteriorate with increasing power. When simultaneous hydride generation and pneumatic nebulization was employed under optimized experimental conditions, detection limits of 3.5, 2.9, 4.3, 1.5 and 2.1 microg L(-1) for As, Bi, Sb, Se and Sn, respectively, were obtained, and the intensities of the analytical lines for elements that do not form volatile hydrides were found to be 40% (Cd), 30% (Ni), 20% (Co, Cr, Fe, Mn and Zn) and 10% (Cu, Mg, V) greater than those obtained when only pneumatic nebulization was used. PMID- 20582405 TI - The influence of intracellular storage material on bacterial identification by means of Raman spectroscopy. AB - Previous studies dealing with bacterial identification by means of Raman spectroscopy have demonstrated that micro-Raman is a suitable technique for single-cell microbial identification. Raman spectra yield fingerprint-like information about all chemical components within one cell, and combined with multivariate methods, differentiation down to species or even strain level is possible. Many microorganisms may accumulate high amounts of polyhydroxyalkanoates (PHA) as carbon and energy storage materials within the cell and the Raman bands of PHA might impede the identification and differentiation of cells. To date, the identification by means of Raman spectroscopy have never been tested on bacteria which had accumulated PHA. Therefore, the aim of this study is to investigate the effect of intracellular polymer accumulation on the bacterial identification rate. Combining fluorescence imaging and Raman spectroscopy, we identified polyhydroxybutyrate (PHB) as a storage polymer accumulating in the investigated cells. The amount of energy storage material present within the cells was dependent on the physiological status of the microorganisms and strongly influenced the identification results. Bacteria in the stationary phase formed granules of crystalline PHB, which obstructed the Raman spectroscopic identification of bacterial species. The Raman spectra of bacteria in the exponential phase were dominated by signals from the storage material. However, the bands from proteins, lipids, and nucleic acids were not completely obscured by signals from PHB. Cells growing under either oxic or anoxic conditions could also be differentiated, suggesting that changes in Raman spectra can be interpreted as an indicator of different metabolic pathways. Although the presence of PHB induced severe changes in the Raman spectra, our results suggest that Raman spectroscopy can be successfully used for identification as long as the bacteria are not in the stationary phase. PMID- 20582406 TI - Determination of different recreational drugs in hair by HS-SPME and GC/MS. AB - A simple procedure combining headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC/MS) to detect and quantify amphetamines, ketamine, methadone, cocaine, cocaethylene and Delta(9)-tetrahydrocannabinol (THC) in hair is described. This procedure allows, in a single sample, even scant, analysis of drugs requiring different analytical conditions. A hair sample (10 mg) is washed and subjected to acidic hydrolysis. Then the HS-SPME is carried out (10 min at 90 degrees C) for amphetamines, ketamine, methadone, cocaine and cocaethylene. For derivatization of analytes, the fibre is introduced into the headspace of another closed vial containing acetic anhydride. After a chromatographic run, an alkaline hydrolysis for THC analysis is carried out in the same vial containing the hair sample previously used. For adsorption, the solid-phase microextraction needle is inserted into the headspace of the vial and the fibre is exposed for 30 min at 150 degrees C. For derivatization of analytes, the fibre is introduced into the headspace of another closed vial containing N methyl-N-(trimethylsilyl)trifluoroacetamide. The GC/MS parameters were the same for both chromatographic runs. The linearity was proved to be between 0.01 and 10.00 ng/mg. The repeatability (intra- and interday precision) was below 10% as the coefficient of variation for all compounds. The accuracy, as the relative recovery, was 96.2-103.5% (spiked samples) and 88.6-101.7% (quality control sample). The limit of detection ranged from 0.01 to 0.12 ng/mg, and the limit of quantification ranged from 0.02 to 0.37 ng/mg. Application of the procedure to real hair samples is described. To the best of our knowledge, the proposed procedure combining HS-SPME and GC/MS is the first one be to successfully applied to the simultaneous determination of most of the common recreational drugs, including THC, in a single hair sample. PMID- 20582407 TI - Raman-based geobarometry of ultrahigh-pressure metamorphic rocks: applications, problems, and perspectives. AB - Raman-based geobarometry has recently become increasingly popular because it is an elegant way to obtain information on peak metamorphic conditions or the entire pressure-temperature-time (P-T-t) path of metamorphic rocks, especially those formed under ultrahigh-pressure (UHP) conditions. However, several problems need to be solved to get reliable estimates of metamorphic conditions. In this paper we present some examples of difficulties which can arise during the Raman spectroscopy study of solid inclusions from ultrahigh-pressure metamorphic rocks. PMID- 20582408 TI - Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis. AB - The role of bacterial infections in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Patients with RA often exhibit periodontal disease, which is associated with pathogens like Porphyromonas gingivalis. The present study examines the direct effects of P. gingivalis on apoptosis of human chondrocytes (a feature of inflammatory joint diseases) as one can assume an interrelation of pathogenesis of RA and P. gingivalis infections. Primary chondrocytes were infected with P. gingivalis. Early apoptotic and dead cell analysis was performed using Annexin-V, 7AAD, and propidium iodide and examined by flow cytometry and fluorescence microscopy. Caspase activation and DNA fragmentation were determined by western blot analysis and TUNEL reaction. Flow cytometry and fluorescence microscopy demonstrated an increase of Annexin-V positive early apoptotic chondrocytes after infection. Western blot showed upregulation of activated caspase-3 expression, and TUNEL reaction revealed considerable DNA fragmentation following infection. The data show that P. gingivalis promotes early and later stages of apoptosis of primary human chondrocytes, which might contribute to the joint damage seen in the pathogenesis of RA. PMID- 20582409 TI - Evidence for the heparin-binding ability of the ascidian Xlink domain and insight into the evolution of the Xlink domain in chordates. AB - The vertebrate Xlink domain is found in two types of genes: lecticans and their associated hyaluronan-and-proteoglycan-binding-link-proteins (HAPLNs), which are components of the extracellular matrix, and those represented by CD44 and stabilins, which are expressed on the surface of lymphocytes. In both types of genes, Xlink functions as a hyaluronan binding domain. We have already reported that protochordate ascidians possess only the latter type of gene. The present analysis of the expression of ascidian Xlink domain genes revealed that these genes function in blood cell migration and apoptosis. While the Xlink domain is found in various metazoans, including ascidians and nematodes, hyaluronan is believed to be specific for vertebrates. In comprehensive genome surveys for hyaluronan synthase (HAS), we found no HAS gene in ascidians. We also established that hyaluronan is absent from the ascidian body biochemically. Therefore, ascidians possess the Xlink domain, but they lack HA. We recovered one ascidian Xlink domain gene that encoded a heparin-binding protein, although it shows no affinity for hyaluronan. Based on these findings, we conclude that in invertebrates, the Xlink domain serves as heparin-binding protein domain and functions in blood cell migration and apoptosis. Its binding affinity for HA might have been acquired in the vertebrate lineage. PMID- 20582410 TI - Copy number variation and association over T-cell receptor genes--influence of DNA source. AB - Genomic copy number variants (CNVs) are a common, heritable source of inter individual differences in genomic sequence. Their influence on phenotypic variability and their involvement in the pathogenesis of several common diseases is well established and the object of many current studies. In the course of examining CNV association to various quantitative traits in a general population, we have detected a strong association of CNVs over the four TCR genes to lymphocyte and neutrophil numbers in blood. In a small replication series, we have further characterized the nature of these CNVs and found them not to be germline, but dependent on the origin of analysed DNA. Germline deletion and rearrangement around the T-cell receptor (TCR) genes naturally occurs in white blood cells. Blood DNA derived from persons with high lymphocyte counts generates variable intensity signals which behave like germline CNVs over these genes. As DNA containing a relative high proportion of these CNV-like events involving the TCR genes has the ability to influence genotype counts of SNPs in the regions of these genes, care should be taken in interpreting and replicating association signals on variants within these genes when blood-derived DNA is the only source of data. PMID- 20582411 TI - Identifying diazotrophs by incorporation of nitrogen from (15)N(2) into RNA. AB - The diversity and abundance of active diazotrophs was investigated in a New Zealand pulp and paper wastewater by enrichment with (15)N(2). Purified (15)N-RNA was analysed by reverse transcription, molecular cloning and sequence analysis of 16S rRNA to reveal a diverse community of bacteria as indicated by a Shannon Weaver Index value of > 2.8. The major class represented in the enriched culture were the gamma-Proteobacteria at 85% with a secondary group of the phylum Firmicutes present at 8.2%, the remaining sequences were affiliated with the alpha- and beta-Proteobacterial classes (1.4% and 4.3%, respectively). Three dominant genera, Aeromonas, Pseudomonas and Bacillus, were identified by comparison with published sequences and phylogenetic analysis. To confirm that representatives of the taxonomic groups identified from the active enriched nitrogen-fixing community were capable of fixing nitrogen Aeromonas and Pseudomonas species were cultivated and shown to possess nifH genes. In wastewater, fluorescence in situ hybridisation probing revealed that the dominant nitrogen-fixing population identified in this study were present in the population, but at lower levels. The population is, therefore, reliant on a small sub-population of diazotrophs to supply the community's nitrogen needs above that already present in the wastewater. PMID- 20582412 TI - Effect of heavy training in contact sports on MRI findings in the pubic region of asymptomatic competitive athletes compared with non-athlete controls. AB - OBJECTIVE: Bone marrow edema (BME) at the pubic symphysis on magnetic resonance imaging (MRI) is usually associated with groin pain and stress injury of the pubic bone. Little is known of the pubic MR imaging findings of asymptomatic heavy training athletes in contact sports. MATERIALS AND METHODS: Pelvic MRI of male asymptomatic soccer (n=10), ice hockey (n=10), bandy (n=10) and female floor ball players (n=10) were compared with non-athlete controls (10 males, 10 females) without groin pain to analyse the presence of BME (on a four-point scale). To study the possible changes of BME directly following heavy physical activity, 10 bandy players underwent MRI before and immediately after a 2-h training session. RESULTS: Magnetic resonance imaging showed minimal BME (grade 1) at the pubic symphysis in 19 of the 40 athletes (48%). Two soccer and 2 ice hockey players (20%) had moderate grade 2 pubic edema, but severe grade 3 BME findings were not found. Also 10 out of 20 (50%) of controls had grade 1 BME. The extent of increased signal was equally distributed in the asymptomatic athletes of different contact sports and controls. A heavy 2-h training session did not cause any enhanced signal at the pubic symphysis. CONCLUSIONS: This study indicates that the presence of grade 1 pubic BME was a frequent finding in contact sports and comparable to that in non-athletes. Grade 2 BME was found only in asymptomatic athletes undergoing heavy training. PMID- 20582413 TI - Aminobisphosphonate-pretreated dendritic cells trigger successful Vgamma9Vdelta2 T cell amplification for immunotherapy in advanced cancer patients. AB - Hepatocellular carcinoma (HCC) and colorectal carcinoma with hepatic metastases (mCRC) are cancers with poor prognosis and limited therapeutic options. New approaches are needed and adoptive immunotherapy with Vgamma9Vdelta2 T lymphocytes represents an attractive strategy. Indeed, Vgamma9Vdelta2 T cells were shown to exhibit efficient lytic activity against various human tumor cell lines, and in vitro Vgamma9Vdelta2 T expansion protocol based on single phosphoantigen stimulation could be easily performed for healthy donors. However, a low proliferative response of Vgamma9Vdelta2 T cells was observed in about half of the cancer patients, leading to an important limitation in the development of Vgamma9Vdelta2 T cell-based immunotherapy. Here, for the first time in the context of cancer patients, Vgamma9Vdelta2 T cell expansions were performed by co culturing peripheral blood mononuclear cell (PBMCs) with autologous dendritic cells (DCs) pretreated with aminobisphosphonate zoledronate. For patients not responding to the conventional culture protocol, co-culture of PBMC with zoledronate-pretreated DCs induced strong cell expansion and allowed reaching a minimal rate of purity of 70% of Vgamma9Vdelta2 T cells. The potent immunostimulatory activity of zoledronate-treated DCs was associated with higher amount of isopentenyl pyrophosphate (IPP) in the culture and was correlated with better ability to activate Vgamma9Vdelta2 T cells as measured by IFN-gamma production. Moreover, we demonstrated that the cytotoxic level of Vgamma9Vdelta2 T cells against freshly autologous tumor cells isolated from patients could be significantly increased by pretreating the tumor cells with zoledronate. Thus, this method of generating Vgamma9Vdelta2 T cells leads eligible for Vgamma9Vdelta2 T cell adoptive immunotherapy the HCC and mCRC patients. PMID- 20582414 TI - Response of soil inorganic nitrogen to land use and topographic position in the Cofre de Perote volcano (Mexico). AB - This study addressed the effects of land use and slope position on soil inorganic nitrogen and was conducted in small watersheds. The study covered three land use types: tropical cloud forest, grassland, and coffee crop. To conduct this research, typical slope small watersheds were chosen in each land use type. Slopes were divided into three positions: shoulder, backslope, and footslope. At the center of each slope position, soil sampling was carried out. Soil inorganic nitrogen was measured monthly during a period of 14 months (July 2005-August 2006) with 11 observations. Significant differences in soil NH(4) (+)-N and NO(3) (-)-N content were detected for both land use and sampling date effects, as well as for interactions. A significant slope position-by-sampling date interaction was found only in coffee crop for NO(3) (-)-N content. In tropical cloud forest and grassland, high soil NH(4) (+)-N and low NO(3) (-)-N content were recorded, while soil NO(3) (-)-N content was high in coffee crop. Low NO(3) (-)-N contents could mean a substantial microbial assimilation of NO(3) (-)-N, constituting an important mechanism for nitrogen retention. Across the entire land use set, the relationship between soil temperature and soil inorganic N concentration was described by an exponential decay function (N = 33 + 2459exp(-0.23T), R (2) = 0.44, P < 0.0001). This study also showed that together, soil temperature and gravimetric soil water content explained more variation in soil inorganic N concentration than gravimetric soil water content alone. PMID- 20582415 TI - Endocrine and bone disease in appropriately treated adult patients with beta thalassemia major. AB - With the optimization of transfusional and chelation regimens, beta-thalassemia has changed from a pediatric disease with poor life expectancy into a chronic disease. Bone demineralization is an important cause of morbidity in older patients; the etiology is multifactorial and partially unknown. We examined, cross-sectionally, 111 adult patients with beta-thalassemia major (66 females and 45 males, 32.6 +/- 6 years) who were regularly transfused, sufficiently chelated and replaced for endocrine defects. Bone demineralization was detected in 92.7% of patients with different severity according to gender and site: osteopenia was the prominent finding at the femur, osteoporosis at the lumbar spine (p < 0.001), more evident in males. The femoral site was more influenced by biochemical and clinical factors; despite adequate replacement, the femoral T-score was lower in the hypogonadic group than in the eugonadic group (p = 0.047). A significant correlation was found between the bone mass and body mass index (BMI), alkaline phosphatase (ALP), and pre-transfusional Hb levels. The multivariate analysis indicated as significant regressors ALP, BMI and hypoparathyroidism (T-score, p = 0.005, 0.035, and 0.002; Z-score, 0.002, 0.009, and 0.003, respectively) at the femoral site; whereas, only ALP at the lumbar spine (p = 0.008 and 0.045 for T and Z-scores, respectively). The statistical significance was reached more frequently by the T-score, while the Z-score seemed to be a less sensitive parameter. Despite best care facilities, bone demineralization in thalassemic patients remains a challenge. Further exploration of the relationships between bone loss and endocrine, biochemical and hematologic parameters is warranted to find effective measures to reduce the risk of fracture in this disease. PMID- 20582416 TI - Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. AB - PURPOSE: Doxorubicin is a mainstay of cancer chemotherapy despite its clinical limitations that arise from its cardiotoxicity and the high incidence of multi drug resistance. Recent studies revealed a protective effect of thymoquinone, a non-toxic constituent of the essential oil of Nigella sativa, against doxorubicin induced cardiotoxicity. We now investigated the influence of thymoquinone on various other effects exerted by doxorubicin in human cancer cells. METHODS: Doxorubicin, thymoquinone and equimolar mixtures of both were tested for cytotoxicity on human cells of HL-60 leukaemia, 518A2 melanoma, HT-29 colon, KB V1 cervix, and MCF-7 breast carcinomas as well as multi-drug-resistant variants thereof and on non-malignant human fibroblasts (HF). Apoptosis induction was analysed via DNA fragmentation, activity studies of the caspases-3, -8 and -9, determination of changes in the mitochondrial membrane potential and in the ratio of the mRNA expressions of pro- and anti-apoptotic proteins bax and bcl-2. The generation of reactive oxygen species (ROS) was assessed by the NBT assay. RESULTS: Thymoquinone improved the anti-cancer properties of doxorubicin in a cell line-specific manner. We found a significant rise of the growth inhibition by doxorubicin in HL-60 and multi-drug-resistant MCF-7/TOPO cells when thymoquinone had been added. The mode of action of both drugs and of their mixture was mainly apoptotic. In HL-60 cells, the drug mixture caused an additional concentration maximum of effector caspase-3 not observed for either of the pure drugs. The impact of the drug mixture on the mitochondria of HL-60 cells was also greater than those of the individual quinones alone. In addition, the drug mixture led to a higher concentration of reactive oxygen species in HL-60 cells. CONCLUSIONS: In summary, thymoquinone is a booster for the anti-cancer effect of doxorubicin in certain cancer cell lines. Distinct improvements on efficacy, selectivity, and even breaches of multi-drug resistance were observed for equimolar mixtures of doxorubicin and thymoquinone. PMID- 20582417 TI - Population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with cancer. AB - Clofarabine for injection is a second-generation nucleoside analog approved in the United States (Clolar((r))) and Europe (Evoltra((r))) for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. This report describes the population pharmacokinetics of clofarabine and its metabolite 6 ketoclofarabine in adult and pediatric patients with hematologic malignancies or solid tumors. Clofarabine pharmacokinetics were best described by a 2-compartment model with linear elimination and first-order absorption after oral administration. Clofarabine was rapidly absorbed following oral administration with a mean absorption time of less than 2 h and bioavailability of 57.5%. The important covariates affecting clofarabine pharmacokinetics were age, weight, and estimated creatinine clearance (eCrCL). No difference in pharmacokinetics was observed between sexes, races, or disease type. The elimination half-life was dependent on all the covariates but was generally less than 7 h in all cases. A difference in clofarabine pharmacokinetics was observed between adults and children. For a pediatric patient 3 years old weighing 16 kg with an eCrCL of 138 mL/min/1.73 m(2), the population estimates for total systemic clearance and volume of distribution at steady-state were 18.3 L/h (1.14 L/h/kg) and 92.9 L (5.81 L/kg), respectively. alpha- and beta-half-life were 0.9 and 4.4 h, respectively. For an elderly patient 82 years old weighing 96 kg with an eCrCL of 46 mL/min/1.73 m(2), the population estimates for CL and Vdss were 21.5 L/h (0.22 L/h/kg) and 257.4 L (268 L/kg), respectively. alpha- and beta-half-life were 0.5 and 10.6 h, respectively. Because of the difference in pharmacokinetics, adults have higher exposure than children given a similar dose standardized to body surface area. The exact mechanism of this difference is not understood. As eCrCL decreased, exposure increased due to reduced total systemic clearance. In the case of moderate (eCrCL 30 to 60 mL/min/1.73 m(2)) and severe (eCrCL <30 mL/min/1.73 m(2)) renal impairment, dose reduction may be needed to maintain similar exposure in an equivalent patient of the same age, weight, and normal renal function after both oral and intravenous administration. 6-Ketoclofarabine was a minor metabolite with peak plasma concentrations occurring about 1 h after the start of the infusion and having a metabolite ratio averaging less than 5% and not more than 8% for any particular individual. 6-Ketoclofarabine was rapidly cleared from plasma with an average apparent half-life of 4.9 h (range 3.9 to 6.2 h). No accumulation of 6-ketoclofarabine was observed with predose samples all below the limit of quantification on Days 8 and 15. Further monitoring of 6 ketoclofarabine is not required in future studies. PMID- 20582418 TI - GA3 stimulates the formation and germination of somatic embryos and the expression of a KNOTTED-like homeobox gene of Cocos nucifera (L.). AB - The micropropagation of coconut palm has progressed rapidly; yet, there are constraints with regard to the number of somatic embryos formed and their germination. To overcome these, we tested the effect of gibberellic acid and characterized genes of the KNOX family. Gibberellic acid at 0.5 muM increased 1.5 fold the number of calli forming somatic embryos and twofold the number of somatic embryos per callus, calli with germinating embryos and the number of germinating somatic embryos per callus. With regard to the study of KNOX family genes, the complete sequences of two KNOX-like genes were obtained for CnKNOX1 and CnKNOX2. The deduced amino acid sequence of both showed highly conserved domains characteristic of KNOX genes. CnKNOX1 showed high homology with KNOX class I proteins. CnKNOX1 expression was detected throughout the embryogenesis process except in somatic embryos at the pro-globular stage, and was highest in somatic embryos at the coleoptilar stage. No detection of CnKNOX1 expression occurred in calli with aberrant embryos. The addition of gibberellic acid stimulated the expression of CnKNOX1 earlier and the relative expression at all stages was higher. CnKNOX2 expression occurred at all stages peaking at the globular stage, but gibberellic acid treatment decreased the expression. Gene expression was also analyzed in tissues of different organs of adult palms. With CnKNOX1, high level of expression was found in tissues of organs with, but not in those without, meristem, whereas CnKNOX2 expression was detected in tissues with and also in those without meristem. PMID- 20582419 TI - Shaker-like potassium channels in Populus, regulated by the CBL-CIPK signal transduction pathway, increase tolerance to low-K+ stress. AB - Shaker-like potassium channels in plants play an important role in potassium absorption and transport. Here, we characterized 11 genes encoding shaker-like channels from Populus trichocarpa. Furthermore, two homologs from this family were isolated from Populus euphratica and named PeKC1 and PeKC2. Subcellular localization analysis of them in Nicotiana benthamiana revealed that they are located in the cell membrane. Yeast two-hybrid assays showed that they not only interacted strongly with PeCIPK24, a homolog of AtCIPK23, but also interacted with several other CIPK members, including PeCIPK10 and PeCIPK17. To further analyze their function, we over-expressed PeKC1 or PeKC2 in akt1 mutant, the results show that the transgenic plant can recover the mutant phonotype sensitive to low-K(+) stress. This means PeKC1 or PeKC2 can complement the function of AKT1 in akt1 mutant, involved in the CBL1-CIPK23 signal transduction pathway and play an important role under low-K(+) stress. PMID- 20582420 TI - Echolocation behaviour of Megaderma lyra during typical orientation situations and while hunting aerial prey: a field study. AB - Bats modify the structure and emission pattern of their calls to cope with the functional constraints of a given echolocation situation. As a consequence, the flexibility in sonar call use affects the potential niche use of a species. The present paper addresses call use in Megaderma lyra, a species with a short, broadband multiharmonic basic call, in typical orientation situations, when emerging from and re-entering a day roost, in cruising flight and when passing through vegetation, and during the pursuit of tethered, flying insects. While call duration and emission rate were adapted to the four orientation situations, call spectral composition was similar in these situations, except that bats emitted calls containing more harmonics when re-entering the roost. These moderate call modifications may be accounted for by the observation that M. lyra stayed close to landscape elements even in open habitats. Although M. lyra is a typical gleaner, all tested bats approached flying insects, guided by sonar calls of significantly decreasing duration and pulse interval, and of increasing sweep rate. Before capture, peak frequency was lowered from call to call. The spontaneous approaches towards flying insects with systematic changes in call pattern suggest regular aerial hunting in this species. PMID- 20582421 TI - Endovascular management of arteriovenous malformations and other intracranial arteriovenous shunts in neonates, infants, and children. AB - PURPOSE: We discuss the management of cerebral arteriovenous shunts in neonates, infants, and children, with emphasis on our experience with pediatric cerebral arteriovenous malformations (AVMs). The management of vein of Galen malformations is discussed in a separate chapter. METHODS: An all-inclusive retrospective chart review of the endovascular surgery operative record database at the Hyman Newman Institute for Neurology and Neurosurgery at Roosevelt Hospital in NYC was conducted. All consecutive pediatric patients (newborn to 18 years of age) with intracranial arteriovenous shunts who presented from January 1, 2004 to June 16, 2009 were included. RESULTS: A total of 151 consecutive pediatric patients with intracranial arteriovenous shunts were evaluated from the period of January 1, 2004 to June 16, 2009. This included 56 patients with vein of Galen malformations, 48 cerebral AVMs, 11 patients with pial arteriovenous fistulae, six patients with dural arteriovenous malformations, and 30 patients with mixed intracranial vascular malformations. Forty-four patients underwent a total of 163 endovascular embolizations. The complications rate for endovascular embolizations was 6.7% (11 in 163), 5.5% with temporary complications and 1.2% with permanent complications. The mortality rate for the group of patients (excluding patients with vein of Galen malformations) that underwent endovascular embolizations was 0.0%. CONCLUSIONS: Careful clinical observation and timely intervention are important in the management of pediatric patients with intracranial arteriovenous shunts. Trans-arterial endovascular embolization with liquid embolic agents is the treatment of choice for safe stabilization and/or improvement of symptoms in the group of pediatric patients with intracranial arteriovenous malformations. PMID- 20582422 TI - A population-based case-control study of risk factors for neural tube defects in Shenyang, China. AB - PURPOSE: To explore the risk factors for neural tube defects (NTD) in Shenyang, we carried out a population-based case-control study. METHODS: We used chi-square test or Fisher's exact test to evaluate variations in the prevalence by selected covariates. Adjusted odds ratios and 95% confidence intervals were derived from univariate and multivariable conditional logistic models. RESULTS: A history of maternal previous birth defect-affected pregnancy was a risk factor for NTDs (adjusted OR = 4.00, 95%CI = 1.29-12.45). Risks for NTDs were significantly associated with exposure to maternal factors during the periconceptional period such as a history of fever or cold (adjusted OR = 6.36, 95%CI = 3.24-12.52), use of analgesic and antipyretic drugs (adjusted OR = 4.94, 95%CI = 1.79-13.63), oral contraceptive use (adjusted OR 2.06, 95%CI 1.16, 3.68), and passive smoking (adjusted OR = 2.24, 95%CI = 1.04-4.81). Folic acid tablets use and fresh vegetable or fruit consumption >=6 meals a week in periconception appeared to be protective factors (adjusted OR 0.33, 0.55, and 0.40, and 95%CI 0.13-0.44, 0.30 1.01, and 0.21-0.74, respectively). Differences in risk were found between the two most common phenotypes of NTD, anencephaly, and spina bifida. CONCLUSIONS: This study suggests that a history of previous birth defect-affected pregnancy, a history of maternal fever or cold, use of analgesics, antipyretics, and oral contraceptives, exposure to passive smoking, folic acid use, and consumption of fresh vegetable and fruit may be associated with NTD risk. PMID- 20582423 TI - Plasma folate concentrations after a single dose ingestion of whole and skimmed folic acid fortified milks in healthy subjects. AB - BACKGROUND: Since mandatory folic acid fortification of grains and cereals was introduced in order to prevent neural tube defects, the number of products that are being fortified with folic acid is growing, especially milk and dairy products. However, the effectiveness of this action remains controversial. AIM OF THE STUDY: To investigate the efficiency of skimmed milk as a vehicle for folic acid fortification by the determination of the acute absorption from low-fat fortified milk compared to fortified and unfortified whole milk in healthy subjects. DESIGN: A single-dose bioavailability study was performed using three commercially available milks (whole and skimmed milk fortified with folic acid and unfortified whole milk). Healthy volunteers (3 women, 2 men) were administered a single dose of 430 ml of each milk, at 1-week intervals between test days. Plasma total folate concentrations, at baseline and hourly from 1.5 up to 6.5 h after ingestion, were measured. RESULTS: Plasma folate concentration was significantly increased, when compared to baseline values, 1.5 h after ingestion of skimmed fortified milk, and 2.5 h after whole fortified milk, and remained significantly higher than baseline values for up to 6.5 h after both treatments. The highest plasma folate concentration (20.9 +/- 3.1 nmol/l) was obtained 6.5 h postprandial in response to skimmed fortified milk. The acute absorption of folic acid, calculated on the basis of area under the plasma folate concentration curve, was significantly higher from skimmed fortified milk compared to fortified and unfortified whole milk. CONCLUSIONS: The absorption of folic acid from fortified skimmed milk is faster than the absorption of folic acid from fortified whole milk, and it renders significantly higher plasma folate concentration when compared to whole milk. These findings indicate that skimmed milk could be considered an efficient food matrix for folic acid fortification. PMID- 20582424 TI - Does stereochemistry influence transdermal permeation of flurbiprofen through the rat skin? AB - The possible enantioselectivity in the permeation of the chiral anti-inflammatory drug flurbiprofen across hairless rat skin was studied. The transdermal permeability of individual enantiomers from donor solution containing racemic flurbiprofen (0.1%) and pure enantiomers (0.05%) in isopropyl myristate solution was determined using side-by-side diffusion cells. The permeation profiles of enantiomers (R)- and (S)-flurbiprofen from donor solution containing racemic (RS) flurbiprofen are comparable. When donor solution contained pure enantiomers, marked differences were observed between the permeation rates of (R)- and (S) flurbiprofen. The steady-state flux and permeability coefficient were significantly higher for (R)-flurbiprofen in comparison with (S)-flurbiprofen (the flux ratio R/S = 2.04; p < 0.05). PMID- 20582425 TI - Intravaginal administration of isosorbide mononitrate and misoprostol for cervical ripening and induction of labour: a randomized controlled trial. AB - BACKGROUND: Labor induction in the presence of unfavorable cervix is a common indication for the use of prostaglandins. However, in the last years, there has been a considerable interest in the use of nitrous oxide donors for cervical ripening and labor induction. OBJECTIVE: To evaluate the efficacy and safety of intravaginal administration of NOD isosorbide mononitrate (IMN) plus misoprostol versus misoprostol alone for cervical ripening and induction of labor. SETTING: Department of Obstetrics and Gynecology, Woman's Health Center, Assiut University. METHODS: Two hundred and ninety women scheduled for labor induction were recruited and assigned randomly to IMN or placebo followed by misoprostol 50 MUg. The efficacy of the medication was evaluated by predetermined outcome variables for cervical ripening and induction of labor and delivery. RESULTS: The two groups were comparable with respect to age, parity, gestational age, indication for induction, and Bishop's score. Women receiving IMN plus misoprostol showed significant changes in the Bishop score 6 h after administration as compared to misoprostol plus placebo (8.57 +/- 1.46 vs. 7.6 +/- 1.39 h, P = 0.001), significantly shorter intervals from the beginning of the induction to the beginning of the active phase of labor (10.97 +/- 2.87 vs. 13.91 +/- 2.16 h, P = 0.0004) and from the beginning of induction to the time of delivery (19.56 +/- 3.96 vs. 23 +/- 2.62 P <= 0.001). No significant differences in the incidence of uterine hypersystole, tachysystole and hyperstimulation. Regarding headache, much more women suffer headache in the IMN group (51) with significant difference to placebo group (11). CONCLUSIONS: Using a combination of IMN and misoprostol is more efficient than misoprostol alone in terms of fast cervical ripening and shortening of induction-labour interval. PMID- 20582426 TI - The prognostic significance of optimal debulking in the setting of a complete clinical response for advanced ovarian carcinoma patients receiving maintenance chemotherapy. AB - AIM: We investigated if optimal surgical debulking increases tumor responsiveness to maintenance chemotherapy and improves survival in advanced ovarian cancer patients who previously attained a clinical complete response (CCR) to primary chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed 75 advanced ovarian cancer patients, of whom 43 and 32 underwent optimal versus suboptimal cytoreduction, respectively. All patients exhibited a CCR following 6 cycles of paclitaxel and carboplatin and subsequently received maintenance chemotherapy (paclitaxel 135 mg/m(2); q21 days). RESULTS: The median progression free survival (PFS) for the optimally debulked patients was 35 months, compared to 20 months for the suboptimal population (P = 0.003). Moreover, a Cox model analysis revealed that an increased number of maintenance chemotherapy cycles and optimal surgical reduction significantly correlated with favorable patient PFS (P < 0.001). In regard to overall survival (OS), the patients who had optimal cytoreductive surgery exhibited improved OS results compared to the sub-optimal surgery group (42 vs. 27 months; P < 0.001). However, a Cox model analysis indicated that a greater number of maintenance chemotherapy cycles was a surrogate marker for improved OS (P < 0.001), but surgery type was not (P > 0.05). Duration of overall patient follow-up exceeds 41 months. CONCLUSION: In advanced ovarian cancer patients who achieve a CCR following induction chemotherapy, optimal cytoreduction may confer a greater clinical benefit from a maintenance approach compared to suboptimal cytoreduction. PMID- 20582427 TI - Transvaginal Doppler sonography for evaluation of irregular uterine bleeding with DMPA. AB - BACKGROUND: The main cause for discontinuation of depot medroxyprogesterone acetate (DMPA) use is irregular menstrual bleeding. The exact pathophysiological mechanisms of irregular bleeding have remained unclear. Transvaginal Doppler is a non-invasive method for studying changes in blood flow which may highlight the underlying pathology in those cases with irregular uterine bleeding. The aim of this study was to quantify the uterine and subendometrial microvasculature in DMPA users with irregular bleeding pattern in comparison to DMPA users with amenorrhea. STUDY DESIGN: This is a case control study. Forty users of DMPA were divided into two groups: one group included 20 users with irregular uterine bleeding and the second group included 20 amenorrheic users. Pulsatility index (PI) and resistance index (RI) of uterine and subendometrial blood vessels were determined. Power Doppler Energy was used to quantify the signal percentage of the subendometrial area. RESULTS: There is significant reduction of PI and RI in the uterine artery and subendometrial microvasculature in cases of irregular uterine bleeding. CONCLUSION: Irregular uterine bleeding with DMPA associated with increased perfusion of uterine and subendometrial blood vessels. PMID- 20582428 TI - Breast abscess following nipple piercing: a case report and review of the literature. AB - BACKGROUND: Nipple piercing gains popularity and social acceptance within the last years, especially among young people. The medical literature reports an increase of complications in the post-piercing period. CASE REPORT: We report a case of a young woman, who presented with a light enlargement of the right breast and tenderness in the retroareolar region following nipple piercing 5 months ago. On ultrasound, a poorly marginated hypoechoic lesion was seen which was suspicious of an inflammation. After 1 week of antibiotic therapy, the mass had enlarged. As carcinoma could not be excluded, open biopsy was performed. Histology showed signs of chronic mastitis. CONCLUSION: To date, only a few reports of breast abscess after nipple piercing have been published. With the increasing prevalence of body piercing, it is important to document and report infections which may be discovered many months following piercing. Carcinoma can mimic breast abscess and should be included in the differential diagnosis. PMID- 20582429 TI - Effects of 50-Hz magnetic field exposure on superoxide radical anion formation and HSP70 induction in human K562 cells. AB - Epidemiological studies suggest a correlation between exposure to low-level extremely low-frequency (ELF) magnetic fields (MF) and certain cancers and neurodegenerative diseases. Experimental studies have not provided any mechanism for such effects, although at flux density levels significantly higher than the ones encountered in epidemiological studies, radical homoeostasis and levels of stress response proteins can be affected. Here, we report on the influence of MF exposure (50-Hz sine wave; 1 h; 0.025-0.10 mT; vertical or horizontal MF exposure direction) on different cellular parameters (proliferation, cell cycle distribution, superoxide radical anion, and HSP70 protein levels) in the human leukaemia cell line K562. The positive control heat treatment (42 degrees C, 1 h) did not affect either cell proliferation or superoxide radical anion production but caused accumulation of cells in the G2 phase and increased the stress protein HSP70. MF exposure (0.10 mT, 1 h) did not affect either cell cycle kinetics or proliferation. Both vertical and horizontal MF exposures for 1 h caused significantly and transiently increased HSP70 levels (>twofold), at several flux densities, compared to sham controls and also compared to heat treatment. This exposure also increased (30-40%) the levels of the superoxide radical anion, comparable to the positive control PMA. Addition of free radical scavengers (melatonin or 1,10-phenantroline) inhibited the MF-induced increase in HSP70. In conclusion, an early response to ELF MF in K562 cells seems to be an increased amount of oxygen radicals, leading to HSP70 induction. Furthermore, the results suggest that there is a flux density threshold where 50-Hz MF exerts its effects on K562 cells, at or below 0.025 mT, and also that it is the MF, and not the induced electric field, which is the active parameter. PMID- 20582430 TI - Tremor following ischemic stroke of the posterior thalamus. PMID- 20582431 TI - Subthalamic nucleus deep brain stimulation changes speech respiratory and laryngeal control in Parkinson's disease. AB - Adequate respiratory and laryngeal motor control are essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on respiratory and laryngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of respiratory and laryngeal control, and whether these changes were correlated with limb function and stimulation parameters. Eighteen PD participants with bilateral STN DBS were tested within a morning session after a minimum of 12 h since their most recent dose of anti-PD medication. Testing occurred when DBS was on, and again 1 h after DBS was turned off, and included aerodynamic measures during syllable production, and standard clinical ratings of limb function. We found that PD participants exhibited changes with DBS, consistent with increased respiratory driving pressure (n = 9) and increased vocal fold closure (n = 9). However, most participants exceeded a typical operating range for these respiratory and laryngeal control variables with DBS. Changes were uncorrelated with limb function, but showed some correlation with stimulation frequency and pulse width, suggesting that speech may benefit more from low-frequency stimulation and shorter pulse width. Therefore, high-frequency STN DBS may be less beneficial for speech-related respiratory and laryngeal control than for limb motor control. It is important to consider these distinctions and their underlying mechanisms when assessing the impact of STN DBS on PD. PMID- 20582432 TI - Postural control in 13-year-old soccer players. AB - To evaluate the effect of early systematic soccer training on postural control we measured center-of-pressure (COP) variability, range, mean velocity and frequency in bipedal quiet stance with eyes open (EO) and closed (EC) in 44 boys aged 13 (25 boys who practiced soccer for 5-6 years and 19 healthy boys who did not practice sports). The soccer players had better stability, particularly in the medial-lateral plane (M/L); their COP variability and range were lower than in controls in both EO (p < 0.05) and EC (p < 0.0005) condition indicating that the athletes were less dependent on vision than non-athletes. Improved stability of athletes was accompanied by a decrease in COP frequency (p < 0.001 in EO, and p < 0.04 in EC) which accounted for lower regulatory activity of balance system in soccer players. The athletes had lower COP mean velocity than controls (p < 0.0001 in both visual condition), with larger difference in the M/L than A/P plane (p < 0.00001 and p < 0.05, respectively). Postural behavior was more variable within the non-athletes than soccer players, mainly in the EC stances (p < 0.005 for all COP parameters). We conclude that: (1) soccer training described was efficient in improving the M/L postural control in young boys; (2) athletes developed specific postural strategies characterized by decreased COP frequency and lower reliance on vision. PMID- 20582433 TI - Diagnostic score for acute appendicitis: is it actually useful? PMID- 20582434 TI - Host-derived suppression of nematode reproductive and fitness genes decreases fecundity of Heterodera glycines Ichinohe. AB - To control Heterodera glycines Ichinohe (soybean cyst nematode) in Glycine max (L.) Merr. (soybean), we evaluated the use of producing transgenic soybean seedlings expressing small interfering RNAs (siRNAs) against specific H. glycines genes. Gene fragments of three genes related to nematode reproduction or fitness (Cpn-1, Y25 and Prp-17) were PCR-amplified using specific primers and independently cloned into the pANDA35HK RNAi vector using a Gateway cloning strategy. Soybean roots were transformed with these constructions using a composite plant system. Confirmation of transformation was attained by PCR and Southern blot analysis. Transgene expression was detected using reverse transcription PCR (RT-PCR) and expression of siRNAs was confirmed in transgenic plants using northern blot analysis. Bioassays performed on transgenic composite plants expressing double-stranded RNA fragments of Cpn-1, Y25 and Prp-17 genes resulted in a 95, 81 and 79% reduction for eggs g(-1) root, respectively. Furthermore, we demonstrated a significant reduction in transcript levels of the Y25 and Prp-17 genes of the nematodes feeding on the transgenic roots via real time RT-PCR whereas the expression of non-target genes were not affected. The results of this study demonstrate that over-expression of RNA interference constructs of nematode reproduction or fitness-related genes can effectively control H. glycines infection with levels of suppression comparable to conventional resistance. PMID- 20582435 TI - Involvement of PTEN/Akt signaling in capsular invasive carcinomas developed in a rat two-stage thyroid carcinogenesis model after promotion with sulfadimethoxine. AB - PURPOSE: Rat thyroid follicular cell carcinomas invading into the thyroid capsule are highly produced by promotion with sulfadimethoxine (SDM) in a rat two-stage thyroid carcinogenesis model. In this study, we investigated the participation of phosphoinositide 3-kinase (PI3K) signaling pathway that is associated with malignant phenotypes of many cancers on the development of SDM-induced capsular invasive carcinomas. METHODS: Thyroid proliferative lesions developed 10 or 15 weeks after promotion with SDM in male F344 rats initiated with N-bis(2 hydroxypropyl)nitrosamine were immunohistochemically analyzed with regard to cellular distribution of phosphatase and tensin homolog (PTEN) and Akt isoforms, as well as their downstream molecules. RESULTS: Increased expression of PI3K signaling molecules was evident in association with the development of lesion stages from the early focal hyperplasia to the late carcinomas. Capsular carcinomas, and the less frequent parenchymal carcinomas, exclusively expressed phosphorylated, inactive PTEN, and active Akt isoforms, as did their downstream molecules. Among the Akt isoforms, enhanced expression of Akt1 was more prominent than that of Akt2 in both capsular and parenchymal carcinomas. CONCLUSIONS: Activation of the PI3K pathway through phosphorylation of PTEN promotes the high production of capsular carcinomas as well as the development of less frequent parenchymal carcinomas. PMID- 20582437 TI - Biliary parasite Pseudamphistomum truncatum (Opistorchiidae) in American mink (Mustela vison) and Eurasian otter (Lutra lutra) in Ireland. AB - Native Eurasian otter (Lutra lutra) and introduced American mink (Mustela vison) carcasses collected throughout Ireland were screened for biliary parasites. Secondary intermediate hosts, Cyprinid fish, were also examined for Opistorchiid metacercariae. Twenty-nine mink and 24 otter gall bladders were screened for biliary parasites. A single mink and three otters were found to be infected with the digenetic trematode Pseudamphistomum truncatum. Eighty-nine percent of roach (Rutilus rutilus) from the River Shannon were infected with P. truncatum metacercariae, confirming the persistence of the parasite. This is the first record of the species in Ireland, and its recent introduction is probably related to the movement and release of Cyprinid fishes by anglers. PMID- 20582436 TI - Molecular cloning and characterization of a gene encoding methionine aminopeptidase 2 of Schistosoma japonicum. AB - Methionine aminopeptidase 2 (MAP2) is an essential enzyme that is involved in protein maturation. It plays a key role in the removal of the initiating methionine residue from nascent polypeptide chains. In the present study, a gene encoding methionine aminopeptidase 2 of Schistosoma japonicum (SjMAP2) was cloned and characterized. Real-time RT-PCR and Western blot analysis revealed that this was expressed in each testing developmental stage in S. japonicum, but more highly expressed at 42 days in male adult worm, suggesting this gene as male differentially expressed. The results also showed that the gene was differentially expressed in worms from three different host species. It was highly expressed in worms from the schistosome-susceptible mouse, expressed at a lower level in worms from the less susceptible rat, and at an even lower level in worms from the non-permissive host Microtus fortis. The expression of the gene was affected significantly when the hosts were treated with praziquantel: Expression was down-regulated by 92.17% and 49.01%, respectively, in treated male and female adult worms in comparison with untreated worms. An immuno-experiment in mice indicated that vaccination with recombinant SjMAP2 could induce partial protective efficacy against schistosome infection. The data presented here suggest that SjMAP2 is an important molecule in the development of the schistosome and that it may be a potential new drug target or vaccine candidate for schistosomiasis. PMID- 20582438 TI - Molecular cloning and expression profiles of Argonaute proteins in Schistosoma japonicum. AB - Small non-coding RNAs including microRNAs and small interfering RNAs play important roles in many biological processes of many organisms. Argonaute proteins serve as a key component of the RNA-induced silencing complex for mediating miRNA/siRNA functions. In the present study, we systematically investigated Argonaute proteins in Schistosoma japonicum by using bioinformatics in combination with 5'- and 3'-Rapid Amplification of cDNA ends techniques and thus obtained three full-length cDNAs encoding Argonaute proteins, named as SjAgo1, SjAgo2, and SjAgo3, respectively. Additionally, SjAgo1/2/3 were differentially expressed in different developmental stages of schistosomes as determined by real-time RT-PCR and Western blot. Taken together, our preliminary results suggested that SjAgo1/2/3 may control gene expression during the life cycle of S. japonicum and therefore may regulate schistosome development and other biological processes. PMID- 20582439 TI - Non-native grass invasion suppresses forest succession. AB - Multiple factors can affect the process of forest succession including seed dispersal patterns, seedling survival, and environmental heterogeneity. A relatively understudied factor affecting the process of succession is invasions by non-native plants. Invasions can increase competition, alter abiotic conditions, and provide refuge for consumers. Functional traits of trees such as seed size and life history stage may mediate the effects of invasions on succession. We tested the effects of the forest invader Microstegium vimineum on planted and naturally regenerating trees in a multi-year field experiment. We established plots containing nine species of small- and large-seeded tree species planted as seeds or saplings, and experimentally added Microstegium to half of all plots. Over 3 years, Microstegium invasion had an overall negative effect on small-seeded species driven primarily by the effect on sweetgum, the most abundant small-seeded species, but did not affect large-seeded species such as hickory and oak species, which have more stored seed resources. Natural regeneration was over 400% greater in control than invaded plots for box elder, red maple, and spicebush, and box elder seedlings were 58% smaller in invaded plots. In contrast to the effects on tree seedlings, invasion did not affect tree sapling survival or growth. Microstegium may be directly reducing tree regeneration through competition. Invaded plots had greater overall herbaceous biomass in 2006 and 2008 and reduced light availability late in the growing season. Indirect effects may also be important. Invaded plots had 120% more thatch biomass, a physical barrier to seedling establishment, and significantly greater vole damage to tree saplings during 2006 and 2007. Our results show that two tree functional traits, seed size and life history stage, determined the effects of Microstegium on tree regeneration. Suppression of tree regeneration by Microstegium invasions may slow the rate of forest succession and alter tree species composition. PMID- 20582440 TI - Drought negatively affects communities on a foundation tree: growth rings predict diversity. AB - Understanding how communities respond to extreme climatic events is important for predicting the impact of climate change on biodiversity. The plant vigor and stress hypotheses provide a theoretical framework for understanding how arthropods respond to stress, but are rarely tested at the community level. Following a record drought, we compared the communities of arthropods on pinyon pine (Pinus edulis) that exhibited a gradient in physical traits related to environmental stress (e.g., growth rate, branch dieback, and needle retention). Six patterns emerged that show how one of the predicted outcomes of climate change in the southwestern USA (i.e., increased drought severity) alters the communities of a foundation tree species. In accordance with the plant vigor hypothesis, increasing tree stress was correlated with an eight to tenfold decline in arthropod species richness and abundance. Trees that were more similar in their level of stress had more similar arthropod communities. Both foliage quantity and quality contributed to arthropod community structure. Individual species and feeding groups differed in their responses to plant stress, but most were negatively affected. Arthropod richness (r(2) = 0.48) and abundance (r(2) = 0.48) on individual trees were positively correlated with the tree's radial growth during drought. This relationship suggests that tree ring analysis may be used as a predictor of arthropod diversity, which is similar to findings with ectomycorrhizal fungi. A contrast of our findings on arthropod abundance with published data on colonization by mutualistic fungi on the same trees demonstrates that at low stress these two communities respond differently, but at high stress both are negatively affected. These results suggest that the effect of extreme climatic events such as drought on foundation tree species are likely to decrease multi-trophic diversity and shift arthropod community composition, which in turn could cascade to affect other associated taxa. PMID- 20582442 TI - Non-erosive reflux disease rather than cervical inlet patch involves globus. AB - BACKGROUND: Gastroesophageal reflux is the most favored etiology for globus; however, recent studies suggest that a cervical inlet patch (heterotopic gastric mucosa in the cervical esophagus) involves globus. This study aimed to reveal whether these two conditions were associated with globus. METHODS: A prospective cross-sectional survey was conducted for 2116 consecutive patients who underwent esophagogastroduodenoscopy in our hospital. Patients were interviewed about globus sensations and reflux symptoms prior to endoscopy. Non-erosive reflux disease was considered with reflux symptoms without reflux esophagitis. Inlet patch was detected using narrow-band imaging. RESULTS: Sixty-three patients were excluded, and of the remaining 2053 patients (1117 male, 61 years old on average), 120 (5.8%) and 284 (13.8%) had globus and inlet patch, respectively. Multivariate analysis (n = 1584) following the exclusion of proton pump inhibitor users revealed that female gender, younger age (<60), inlet patch, and reflux symptoms were independent risk factors for the development of globus; however, reflux esophagitis was an independent factor for reducing the development of globus. In a reanalysis of non-erosive reflux disease instead of reflux symptoms, inlet patch and non-erosive reflux disease were independent risk factors for the development of globus (odds ratio, 2.9 and 12.1, respectively). CONCLUSIONS: Non erosive reflux disease was more closely associated with globus than an inlet patch. Our controversial results indicating a strong association of globus with non-erosive reflux disease and an inverse association of globus with reflux esophagitis may suggest that mechanisms other than gastroesophageal reflux as the etiology, such as an esophageal visceral hypersensitivity, involve globus. PMID- 20582443 TI - Oral health-related quality of life is linked with subjective well-being and depression in early old age. AB - Although a body of research has targeted predictors of well-being and depression in old age, the consideration of oral health-related quality of life (OHRQoL) as a predictor of these major psychosocial endpoints has been rare in the previous literature. The objective of this study was to test whether OHRQoL is associated with well-being and depression, after controlling for relevant confounders; also, the mediating role of subjective health, a major predictor of both well-being and depression, has been explored. OHRQoL was measured by two commonly used assessment instruments, the geriatric oral health assessment index (GOHAI) and oral health impact profile (OHIP); well-being was assessed by the Philadelphia Geriatric Center Morale Scale (PGCMS) and depression by the self-rating depression scale (SDS). We used a subsample of 197 participants from the older cohort (1930-1932) of the Interdisciplinary Longitudinal Study of Adult Development. Regression models and structural equations modeling (SEM) were used for the test for study variable relationships. Both GOHAI and OHIP revealed significant associations to both PGCMS and SDS at the bivariate level. In regression analyses considering gender, household situation, subjective health, and both OHRQoL indicators, only OHIP remained a significant predictor of well being and depression. In addition, supportive evidence for a mediating role of subjective health regarding the linkage between OHRQoL and an overall latent construct of well-being was found in the SEM analysis. In conclusion, OHRQoL is significantly linked with well-being and depression in old age, while subjective health is able to mediate the relationship. The generally underrated role of OHRQoL with respect to well-being and depression in late adulthood deserves more attention. PMID- 20582445 TI - Salmonellae in food stuffs of plant origin and their implications on human health. AB - Salmonella enterica is one of the most common causes of food-borne infection in human beings. Cases of Salmonella infection have been decreasing in Europe in the last ten years, yet, Salmonella infections are still the main cause of acute diarrhea syndrome. Globalization has caused the international food industry to increase the production of collective nutrition produce and products. This has intensified the need for authorized and accredited laboratories to monitor microbiological food safety. All parameters indicate the necessity of a multi sector approach to this problem. Food safety supervision involves the analysis and identification of risk management, as well as the monitoring, evaluating, and regulating of crop irrigation. We can be more certain with a multi-sector approach that the number of Salmonella infections caused by plant-originated food stuffs will not increase in the future. PMID- 20582446 TI - Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction. AB - It has been proposed that it is not necessary to adjust the dose of linezolid (LZD) in patients with reduced renal function. However, significantly lower platelet counts and hemoglobin levels have been reported in such patients compared to those in patients with normal renal function. This suggests that the appropriate dose and administration method for LZD are yet to be established in patients with renal dysfunction. The subjects in this study were patients with renal dysfunction who developed adverse effects of thrombocytopenia and anemia during treatment with LZD. We investigated the association of these adverse effects with the blood LZD concentration and the area under the concentration time curve from zero to 24 h (AUC(0-24)), determined using a one-compartment Bayesian model (n = 20). The measured blood LZD concentration was significantly higher than the predicted concentration in a population pharmacokinetics approach (p < 0.01), and severe thrombocytopenia developed as the blood LZD concentration increased. The platelet count and hemoglobin level decreased as the AUC(0-24) of LZD increased in patients with renal dysfunction, and the correlations were significant: r = 0.593 and r = 0.783, respectively (p < 0.01). These findings suggest that LZD administered to patients with renal dysfunction may reach a high blood level and subsequently increase the AUC(0-24), which may then induce adverse effects of severe thrombocytopenia and anemia. PMID- 20582447 TI - Force networks and elasticity in granular silos. AB - We have made experimental observations of the force networks within a two dimensional granular silo similar to the classical system of Janssen. Models like that of Janssen predict that pressure within a silo saturates with depth as the result of vertical forces being redirected to the walls of the silo where they can then be carried by friction. We use photoelastic particles to obtain information not available in previous silo experiments --the internal force structure. We directly compare various predictions with the results obtained by averaging ensembles of experimentally obtained force networks. We identify several differences between the mean behavior in our system and that predicted by Janssen-like models: We find that the redirection parameter describing how the force network transfers vertical forces to the walls varies with depth. We find that changes in the preparation of the material can cause the pressure within the silo to either saturate or to continue building with depth. Most strikingly, we observe a nonlinear response to overloads applied to the top of the material in the silo. For larger overloads we observe the previously reported "giant overshoot" effect where overload pressure decays only after an initial increase (G. Ovarlez et al., Phys. Rev. E 67, 060302(R) (2003)). For smaller overloads we find that additional pressure propagates to great depth. Analysis of the differences between the inter-grain contact and force networks suggests that, for our system, when the load and the particle weight are comparable, particle elasticity acts to stabilize the force network, allowing deep propagation. For larger loads, the force network rearranges, resulting in the expected, Janssen like behavior. Thus, a meso-scale network phenomenon results in an observable nonlinearity in the mean pressure profile. PMID- 20582448 TI - Ligamentum flavum cyst in the lumbar spine: a case report and review of the literature. AB - Degenerative changes in the lumbar spine can be followed by cystic changes. Most reported intraspinal cysts are ganglion or synovial cysts. Ligamentum flavum pseudocyst, as a cystic lesion in the lumbar spine, is a rare and unusual cause of neurologic signs and symptoms and is usually seen in elderly persons (due to degenerative changes). They are preferentially located in the lower lumbar region, while cervical localization is rare. Complete removal of the cyst leads to excellent results and seems to preclude recurrence. We report the case of a right-sided ligamentum flavum cyst occurring at L3-L4 level in a 70-year-old woman, which was surgically removed with excellent postoperative results and complete resolution of symptoms. In addition, we discuss and review reports in the literature. PMID- 20582449 TI - Unexplained changes in tilt table test outcomes after moving to a new laboratory. PMID- 20582450 TI - Rab protein evolution and the history of the eukaryotic endomembrane system. AB - Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity. PMID- 20582451 TI - Factor binding and chromatin modification in the promoter of murine Egr1 gene upon induction. AB - The influence of chromatin on immediate-early gene expression has been studied in a model of Egr1 induction in intact mouse cells. ChIP analysis of factor and RNA polymerase binding reveals that the gene is constitutively poised for transcription in nonstimulated cells, but a repressing chromatin structure hampers productive transcription. Stimulation with phorbol esters results in a transient activation, which starts at 5 min and peaks at 30 min. Quantitative mapping of promoter occupancy by the different factors shows for the first time that no direct competition between SP1 and EGR1 occurs. The phosphorylation of ELK1 and CREB, which involves both the cascades of MEK1/2 and p38 kinases, is required for gene expression, which ceases following the binding of NAB1 and NAB2 to the promoter. The changes in histone acetylation and the differential recruitment of histone-modifying complexes further show the role of chromatin in the activation of this immediate-early gene. PMID- 20582452 TI - Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. AB - Germ cell tumours (GCTs) are a diverse group of neoplasms all of which are generally believed to arise from germ cell progenitors (PGCs). Even those that form in the nervous system are likewise believed to be PGC-derived, despite being found a great distance from the normal location of germ cells. The primary evidence in favour of this model for the origins of intracranial GCTs is that they share molecular features with other GCTs. Those features include shared gene expression and a lack of methylation of imprinted genes, including SNRPN. Contrary to this model, we have proposed that endogenous neural stem cells of the brain are a more likely origin for these tumours. We show here that the lack of methylation of SNRPN that has previously been taken to indicate an origin for GCTs from PGCs is also seen in neural stem cells of mice and humans. We believe that, in the light of these and other recent observations, endogenous neural precursors of the brain are a more plausible origin for intracranial GCTs than are misplaced PGCs. PMID- 20582453 TI - Evaluation of haloalkaliphilic sulfur-oxidizing microorganisms with potential application in the effluent treatment of the petroleum industry. AB - Haloalkaliphilic sulfur-oxidizing mixed cultures for the treatment of alkaline saline effluents containing sulfide were characterized and evaluated. The mixed cultures (IMP-PB, IMP-XO and IMP-TL) were obtained from Mexican alkaline soils collected in Puebla (PB), Xochimilco (XO) and Tlahuac (TL), respectively. The Ribosomal Intergenic Spacer Analysis (RISA) revealed bacteria related to Thioalkalibacterium and Thioalkalivibrio in IMP-XO and IMP-PB mixed cultures. Halomonas strains were detected in IMP-XO and IMP-TL. In addition, an uncultured Bacteroides bacterium was present in IMP-TL. Mixed cultures were evaluated at different pH and NaCl concentrations at 30 degrees C. IMP-PB and IMP-TL expressed thiosulfate-oxidizing activity in the 7.5-10.5 pH range, whereas IMP-XO presented its maximal activity with 19.0 mg O2 g (protein)-1 min-1, at pH 10.6; it was not affected by NaCl concentrations up to 1.7 M. In continuous culture, IMP-XO showed a growth rate of 15 day-1, productivity of 433.4 mg(protein) l-1 day-1 and haloalkaliphilic sulfur-oxidizing activity was also detected up to 170 mM by means of N-methyl-diethanolamine (MDEA). Saline-alkaline soil samples are potential sources of haloalkaliphilic sulfur-oxidizing bacteria and the mixed cultures could be applied in the treatment of inorganic sulfur compounds in petroleum industry effluents under alkaline-saline conditions. PMID- 20582454 TI - Paclitaxel-loaded, folic-acid-targeted and TAT-peptide-conjugated polymeric liposomes: in vitro and in vivo evaluation. AB - OBJECTIVE: Folic acid and TAT peptide were conjugated on the octadecyl quaternized, lysine-modified chitosan-cholesterol polymeric liposomes (FA-TATp PLs) to investigate their potential feasibility for tumor-targeted drug delivery. METHODS: FA-TATp-PLs encapsulating paclitaxel or calcein were synthesized and characterized. Cellular uptake of PLs, FA-PLs, TATp-PLs and FA-TATp-PLs was studied by confocal laser scanning microscopy (CLSM) in folate receptor (FR) positive KB nasopharyngeal epidermal carcinoma cells and FR-deficient A549 lung cancer cells. In vitro and in vivo antitumor activity of paclitaxel-loaded FA TATp-PLs were also evaluated in KB and A549 cells as well as in a murine KB xenograft model. RESULTS: Our data showed that 80% paclitaxel released from FA TATp-PLs in 2 weeks. Different from other various PLs, CLSM analyses showed that FA-TATp-PLs had a significantly high efficient intracellular uptake in both KB and A549 cells. These data revealed the targeting effects of folate decoration, the transmembrane ability of TAT peptide as well as a synergistic interaction between them. In addition, paclitaxel-loaded FA-TATp-PLs exhibited a more superior antitumor effect in vitro and in vivo as compared to that with Taxol. CONCLUSIONS: FA-TATp-PLs possessing both targeting effect and transmembrane ability may serve as a promising carrier for the intracellular delivery of therapeutic agents. PMID- 20582455 TI - Rapid intradermal delivery of liquid formulations using a hollow microstructured array. AB - PURPOSE: The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. METHODS: 3M's hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. RESULTS: Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. CONCLUSIONS: 3M's hMTS can provide rapid, intradermal delivery of 300-1,500 uL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. PMID- 20582457 TI - Evaluating the Healthy Start program: a life course perspective. PMID- 20582456 TI - The role of the inflammasome in nonmyeloid cells. AB - Inflammasomes are cytosolic multiprotein complexes that can proteolytically activate caspase-1. Activated caspase-1 is needed for the maturation and secretion of interleukin (IL)-1beta and IL-18. In the past decade, there has been tremendous progress in our knowledge of inflammasome function and IL-1 signaling, mainly in cells of the innate immune system, such as monocytes, macrophages, neutrophils, and dendritic cells. Because nonimmune cells, including keratinocytes, synovial cells, or astrocytes, can form an interface between the body and the environment or a defined compartment (brain, joint), they are important guardians for the detection of danger signals and the consecutive initiation of an inflammatory response. They are present in anatomical compartments that are less accessible to myeloid cells and thus can fulfill tasks usually performed by residential macrophages. This review focuses on recent progress in our understanding of the processing and functional role of IL-1 in epithelial, mesenchymal, and neuronal cells and in conditions such as tissue repair. PMID- 20582458 TI - Integrated approaches to improve birth outcomes: perinatal periods of risk, infant mortality review, and the Los Angeles Mommy and Baby Project. AB - This article provides an example of how Perinatal Periods of Risk (PPOR) can provide a framework and offer analytic methods that move communities to productive action to address infant mortality. Between 1999 and 2002, the infant mortality rate in the Antelope Valley region of Los Angeles County increased from 5.0 to 10.6 per 1,000 live births. Of particular concern, infant mortality among African Americans in the Antelope Valley rose from 11.0 per 1,000 live births (7 cases) in 1999 to 32.7 per 1,000 live births (27 cases) in 2002. In response, the Los Angeles County Department of Public Health, Maternal, Child, and Adolescent Health Programs partnered with a community task force to develop an action plan to address the issue. Three stages of the PPOR approach were used: (1) Assuring Readiness; (2) Data and Assessment, which included: (a) Using 2002 vital records to identify areas with the highest excess rates of feto-infant mortality (Phase 1 PPOR), and (b) Implementing Infant Mortality Review (IMR) and the Los Angeles Mommy and Baby (LAMB) Project, a population-based study to identify potential factors associated with adverse birth outcomes. (Phase 2 PPOR); and (3) Strategy and Planning, to develop strategic actions for targeted prevention. A description of stakeholders' commitments to improve birth outcomes and monitor infant mortality is also given. The Antelope Valley community was engaged and ready to investigate the local rise in infant mortality. Phase 1 PPOR analysis identified Maternal Health/Prematurity and Infant Health as the most important periods of risk for further investigation and potential intervention. During the Phase 2 PPOR analyses, IMR found a significant proportion of mothers with previous fetal loss (45%) or low birth weight/preterm (LBW/PT) birth, late prenatal care (39%), maternal infections (47%), and infant safety issues (21%). After adjusting for potential confounders (maternal age, race, education level, and marital status), the LAMB case-control study (279 controls, 87 cases) identified additional factors associated with LBW births: high blood pressure before and during pregnancy, pregnancy weight gain falling outside of the recommended range, smoking during pregnancy, and feeling unhappy during pregnancy. PT birth was significantly associated with having a previous LBW/PT birth, not taking multivitamins before pregnancy, and feeling unhappy during pregnancy. In response to these findings, community stakeholders gathered to develop strategic actions for targeted prevention to address infant mortality. Subsequently, key funders infused resources into the community, resulting in expanded case management of high-risk women, increased family planning services and local resources, better training for nurses, and public health initiatives to increase awareness of infant safety. Community readiness, mobilization, and alignment in addressing a public health concern in Los Angeles County enabled the integration of PPOR analytic methods into the established IMR structure and [the design and implementation of a population-based l study (LAMB)] to monitor the factors associated with adverse birth outcomes. PPOR proved an effective approach for identifying risk and social factors of greatest concern, the magnitude of the problem, and mobilizing community action to improve infant mortality in the Antelope Valley. PMID- 20582461 TI - Community street theatre as a tool for interventions on alcohol use and other behaviors related to HIV risks. AB - This paper presents data on the role and implementation of street theatre as a communications technique for HIV behavioral interventions in low income slum communities in Mumbai. Second, we situate the uses of street theatre as a social intervention strategy within a long history of outdoor drama as entertainment and social action in India. Street theatre with accompanying activities was a central element of the RISHTA project's communications strategy in communities in Mumbai, designed to deliver tailored risk reduction messages to married men who were involved in extramarital relationships. The paper presents examples of the contents and delivery of alcohol risk reduction messages through street plays that were developed and performed by actors from low income communities. The paper situates street plays as part of the domain of prevention strategies, which can be effective in reducing HIV risks, including those related to alcohol use. PMID- 20582459 TI - Neonatal exendin-4 leads to protection from reperfusion injury and reduced rates of oxidative phosphorylation in the adult rat heart. AB - PURPOSE: Glucagon like peptide-1 (7-36) amide (GLP-1) is an incretin hormone with multiple salutary cardiovascular effects. A short course of the GLP-1 analogue Exendin-4 (Ex-4) in the neonatal period prevents the development of mitochondrial dysfunction and oxidative stress in a rat prone to obesity and diabetes. We sought to evaluate whether neonatal Ex-4 can exert the same effect in the normal rat heart, as well as whether Ex-4 could affect susceptibility to cardiac reperfusion injury. METHODS: After birth, Sprague Dawley rat pups were given either Ex-4 (1 nmole/kg body weight) or vehicle (1% BSA in 0.9% saline) subcutaneously for 6 days. Animals were studied at juvenile (4-6 weeks) and adult (8-9 months) ages. Using the Langendorff isolated perfused heart, cardiovascular function was assessed at baseline and following ischemia-reperfusion. Mitochondria were isolated from fresh heart tissue, and oxidative phosphorylation and calcium sequestration were analyzed. TBARS, MnSOD activity, and non-enzymatic anti-oxidant capacity were measured to assess the degree of oxidative stress present in the two groups. RESULTS: Both at the juvenile and adult age, Ex-4 treated rats demonstrated improved recovery from an ischemic insult. Rates of oxidative phosphorylation were globally reduced in adult, but not juvenile Ex-4 treated animals. Furthermore, mitochondria isolated from adult Ex-4 treated rats sequestered less calcium before undergoing the mitochondrial permeability transition. Oxidative stress did not differ between groups at any time point. CONCLUSION: A short course of Exendin-4 in the neonatal period leads to protection from ischemic injury and a preconditioned mitochondrial phenotype in the adult rat. PMID- 20582460 TI - The genome sequence of an H11N2 avian influenza virus from a Thick-billed Murre (Uria lomvia) shows marine-specific and regional patterns of relationships to other viruses. AB - Influenza A viruses infect a range of host species, including various mammals and more than 100 species of birds. For avian influenza viruses (AIV), prevalence varies between different groups of birds, with waterfowl showing the highest prevalence. We have sequenced the complete genome of A/Thick-billed Murre/Newfoundland/031/2007(H11N2), an AIV identified in the pelagic seabird, Thick-billed Murre (Uria lomvia). This represents the first complete genome sequence of an AIV from this host species, and only the second complete genome sequence from a seabird in the alcid group. All of the virus segments fall within the American avian lineage. Several of the segments show a close relationship to AIV identified in other marine host species, and also a strong geographic association with other AIV sequences from the northeastern coast of North America from recent years. The identification of this virus, and the growing number of AIV identified in seabird species, indicates these marine birds could be underappreciated host species. This has potential consequences for global influenza dynamics because of the seasonal distributions and migratory patterns of this group of birds. PMID- 20582462 TI - Community-level HIV/STI interventions and their impact on alcohol use in urban poor populations in India. AB - This paper describes an Indo-US, research and intervention project for HIV/STI prevention and sexual risk reduction in urban poor communities in Mumbai, India in which formative research established the importance of reduction in alcohol use as one of the central features of the intervention. As a part of formative research, in-depth interviews with married women and men indicated that alcohol had a direct negative effect on marital relationships, violence, household economics and men's involvement in extramarital sex. The project utilized diverse community intervention mechanisms over the course of a three year intervention effort. Comparison of pre-post intervention, cross-sectional samples showed a significant drop in overall use of alcohol in the study communities. Analysis of a longitudinal panel sample identified sub-groups of married men based on their demographic, behavioral and attitudinal characteristics at baseline who stopped drinking during the intervention period. Results also demonstrated that a reduction in men's alcohol use during the intervention period was associated with a reduction in sexual risk behavior and related variables. PMID- 20582463 TI - The intra-hippocampal leucine administration impairs memory consolidation and LTP generation in rats. AB - Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder, predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of individuals affected by this deficiency, the mechanisms underlying the neuropathology of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter, long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls) into the hippocampus immediately post training in the behavioral task. Twenty-four hours after training in the step down test, the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements. Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from leucine administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious leucine effect on cognition. PMID- 20582464 TI - DNA repair signature is associated with anthracycline response in triple negative breast cancer patients. AB - We hypothesized that a subset of sporadic triple negative (TN) breast cancer patients whose tumors have defective DNA repair similar to BRCA1-associated tumors are more likely to exhibit up-regulation of DNA repair-related genes, anthracycline-sensitivity, and taxane-resistance. We derived a defective DNA repair gene expression signature of 334 genes by applying a previously published BRCA1-associated expression pattern to three datasets of sporadic TN breast cancers. We confirmed a subset of 69 of the most differentially expressed genes by quantitative RT-PCR, using a low density custom array (LDA). Next, we tested the association of this DNA repair microarray signature expression with pathologic response in neoadjuvant anthracycline trials of FEC (n = 50) and AC (n = 16), or taxane-based TET chemotherapy (n = 39). Finally, we collected paraffin fixed, formalin-embedded biopsies from TN patients who had received neoadjuvant AC (n = 28), and tested the utility of the LDA to discriminate response. Correlation between RNA expression measured by the microarrays and 69-gene LDA was ascertained. This defective DNA repair microarray gene expression pattern was significantly associated with anthracycline response and taxane resistance, with the area under the ordinary receiver operating characteristic curve (AUC) of 0.61 (95% CI = 0.45-0.77), and 0.65 (95% CI = 0.46-0.85), respectively. From the FFPE samples, the 69-gene LDA could discriminate AC responders, with AUC of 0.79 (95% CI = 0.59-0.98). In conclusion, a promising defective DNA repair gene expression signature appears to differentiate TN breast cancers that are sensitive to anthracyclines and resistant to taxane-based chemotherapy, and should be tested in clinical trials with other DNA-damaging agents and PARP-1 inhibitors. PMID- 20582465 TI - PALB2 analysis in BRCA2-like families. AB - BRCA2 and PALB2 function together in the Fanconi anemia (FA)-Breast Cancer (BRCA) pathway. Mono-allelic and bi-allelic BRCA2 and PALB2 mutation carriers share many clinical characteristics. Mono-allelic germline mutations of BRCA2 and PALB2 are risk alleles of female breast cancer and have also been reported in familial pancreatic cancer, and bi-allelic mutations cause a severe form of Fanconi anemia. In view of these similarities, we investigated whether the prevalence of PALB2 mutations was increased in breast cancer families with the occurrence of BRCA2 associated tumours other than female breast cancer. PALB2 mutation analysis was performed in 110 non-BRCA1/2 cancer patients: (a) 53 ovarian cancer patients from female breast-and/or ovarian cancer families; (b) 45 breast cancer patients with a first or second degree relative with pancreatic cancer; and (c) 12 male breast cancer patients from female breast cancer families. One truncating PALB2 mutation, c.509_510delGA, resulting in p.Arg170X, was found in a male breast cancer patient. We conclude that germline mutations of PALB2 do not significantly contribute to cancer risk in non-BRCA1/2 cancer families with at least one patient with ovarian cancer, male breast cancer, and/or pancreatic cancer. PMID- 20582466 TI - Weekly paclitaxel improved pathologic response of primary chemotherapy compared with standard 3 weeks schedule in primary breast cancer. AB - The purpose of this study is to compare the efficacy of weekly paclitaxel to every-3-week schedule in terms of pathologic response and toxicity which caused treatment delay in primary chemotherapy of breast cancer. After pretreatment of two cycles of cyclophosphamide/ pirarubicin/ fluorouracil (cyclophosphamide 500 mg/m(2) days 1, 8; pirarubicin 35 mg/m(2) days 1, 8; 5-Fu 200 mg/m(2) day ci day 1-28, every 4 weeks), 219 women with histologically confirmed T(1-3) N(0-2) M(0) invasive breast cancer, whose vertical diameters production of breast tumor reduced not more than 75%, were randomized to receive four cycles of Pq3wC (arm A: paclitaxel 175 mg/m(2) day 1, carboplatin AUC 6 d1, every 3 weeks) or Pq1wC (arm B: paclitaxel 60 mg/m(2) days 1, 8, 15, carboplatin AUC 6 day 1 for every 3 weeks) before surgery, stratified by partial or no response (stable disease and progression of disease) evaluated by ultrasonography. Pathologic response of the primary tumor was assessed by using Miller and Payne grading system. We defined grade 4/5 as excellent response, grade 3/4/5 as response and treatment delay as paclitaxel administration being delayed at least 1 week because of toxicity in this study. 213 patients (2 cases with concurrent bilateral breast cancer) were eligible for analysis, 109 patients with 110 lesions in arm A and 104 patients with 105 lesions in arm B. Patients in arm B had a higher excellent pathologic response rate and a higher pathologic response rate compared with patients in arm A (59.0 vs. 45.5%, P = 0.046 and 86.7 vs. 71.8%, P = 0.007). Pathologic complete response (pCR) rate in breast alone was similar between two arms (P = 0.733), but there was a higher pCR rate in patients with partial response to two cycles of cyclophosphamide/pirarubicin/fluorouracil than those with no response (32.4 vs. 13.9%, P = 0.001). There was no treatment-related death, however more patients in arm B than in arm A experienced treatment delay caused by toxicity (60.6 vs. 11.9%, P < 0.001). Under the condition of same cumulative doses, weekly paclitaxel was more effective than 3 weeks schedule in terms of pathologic response to primary chemotherapy in breast cancer, and caused more treatment delay related to toxicity though well tolerant. PMID- 20582467 TI - A synthetic globotriaosylceramide analogue inhibits HIV-1 infection in vitro by two mechanisms. AB - Previously, it was shown that the cell-membrane-expressed glycosphingolipid, globotriaosylceramide (Gb(3)/P(k)/CD77), protects against HIV-1 infection and may be a newly described natural resistance factor against HIV infection. We have now investigated the potential of a novel, water soluble, non-toxic and completely synthetic analogue of Gb(3)/P(k) (FSL-Gb(3)) to inhibit HIV-1 infection in vitro. A uniquely designed analogue, FSL-Gb(3), of the natural Gb(3)/P(k) molecule was synthesized. HIV-1(IIIB) (X4 virus) and HIV-1(Ba-L) (R5 virus) infection of PHA/interleukin-2-activated, peripheral blood mononuclear cells (PBMCs) and Jurkat T cells in vitro was assessed, as well as infection of U87.CD4.CCR5 by various clinical R5 tropic viruses after treatment with FSL-Gb(3). We monitored Gb(3), CD4 and CXCR4 expression by fluorescent antibody cell sorting and viral replication by p24(gag) ELISA. Total cellular Gb(3) was examined by glycosphingolipid extraction and thin layer chromatography. In vivo toxicity was monitored in mice by histological assessment of vital organs and lymphoid tissue. FSL-Gb(3) blocked X4 and R5 of both lab and clinical viral strains in activated PBMCs or the U87.CD4.CCR5 cell line with a 50% inhibitory concentration (IC(50)) of approximately 200-250 microM. FACS and TLC overlay showed that FSL-Gb(3) can insert itself into cellular plasma membranes and that cellular membrane-absorbed FSL-Gb(3) is able to inhibit subsequent HIV-1 infection. There was no effect of FSL-Gb(3) on cell surface levels of CD4 or CXCR4. Thus, FSL-Gb(3) can inhibit HIV 1 by two mechanisms: direct inhibition of virus and inhibition of viral entry. Infusion of FSL-Gb(3) into laboratory mice at doses well in excess of theoretical therapeutic doses was tolerated with no untoward reactions. Our results demonstrate the potential utility of using a completely synthetic, water soluble globotriaosylceramide analogue, FSL-Gb(3), having low toxicity, for possible future use as a novel therapeutic approach for the systemic treatment of HIV/AIDS. PMID- 20582469 TI - Bacillus deserti sp. nov., a novel bacterium isolated from the desert of Xinjiang, China. AB - A Gram-positive, rod-shaped, motile and spore-forming bacterium, designated ZLD 8(T), was isolated from a desert soil sample collected from Xinjiang Province in north-west China, and subjected to a polyphasic taxonomic analysis. This isolate grew optimally at 30 degrees C and pH 7.0. It grew with 0-4% NaCl (optimum, 0 1%). Comparative 16S rRNA gene sequence analysis showed that strain ZLD-8(T) was closely related to members of the genus Bacillus, exhibiting the highest 16S rRNA gene sequence similarity to Bacillus kribbensis DSM 17871(T) (98.0%). The levels of 16S rRNA gene sequence similarity with respect to other Bacillus species with validly published names were less than 96.3%. The DNA G + C content of strain ZLD 8(T) was 40.1 mol%. The strain contained MK-7 as the predominant menaquinone. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major fatty acids (>5% of total fatty acids) were anteiso-C15:0 (39.56%), iso-C14:0 (25.69%), C16:1 omega7c alcohol (10.13%) and iso-C15:0 (5.27%). These chemotaxonomic results supported the affiliation of strain ZLD-8(T) to the genus Bacillus. However, low DNA-DNA relatedness values and distinguishing phenotypic characteristics allowed genotypic and phenotypic differentiation of strain ZLD-8(T) from recognized Bacillus species. On the basis of the polyphasic evidence presented, strain ZLD-8(T) is considered to represent a novel species of the genus Bacillus, for which the name Bacillus deserti sp. nov. is proposed. The type strain is ZLD-8(T) (=CCTCC AB 207173(T) = KCTC 13246(T)). PMID- 20582470 TI - Influence of cell surface characteristics on adhesion of Saccharomyces cerevisiae to the biomaterial hydroxylapatite. AB - The influence of the physicochemical properties of biomaterials on microbial cell adhesion is well known, with the extent of adhesion depending on hydrophobicity, surface charge, specific functional groups and acid-base properties. Regarding yeasts, the effect of cell surfaces is often overlooked, despite the fact that generalisations may not be made between closely related strains. The current investigation compared adhesion of three industrially relevant strains of Saccharomyces cerevisiae (M-type, NCYC 1681 and ALY, strains used in production of Scotch whisky, ale and lager, respectively) to the biomaterial hydroxylapatite (HAP). Adhesion of the whisky yeast was greatest, followed by the ale strain, while adhesion of the lager strain was approximately 10-times less. According to microbial adhesion to solvents (MATS) analysis, the ale strain was hydrophobic while the whisky and lager strains were moderately hydrophilic. This contrasted with analyses of water contact angles where all strains were characterised as hydrophilic. All yeast strains were electron donating, with low electron accepting potential, as indicated by both surface energy and MATS analysis. Overall, there was a linear correlation between adhesion to HAP and the overall surface free energy of the yeasts. This is the first time that the relationship between yeast cell surface energy and adherence to a biomaterial has been described. PMID- 20582471 TI - A guide to successful bioprospecting: informed by actinobacterial systematics. AB - New structurally diverse natural products are discovered when novel screening procedures are introduced or when high quality biological materials from new sources are examined in existing screens, hence it is important to foster these two aspects of novelty in drug discovery programmes. Amongst prokaryotes, actinomycetes, notably streptomycetes, remain a rich source of new natural products though it has become increasingly difficult to find such metabolites from common actinomycetes as screening 'old friends' leads to the costly rediscovery of known compounds. The bioprospecting strategy which is the subject of this review is based upon the premise that new secondary metabolites can be found by screening relatively small numbers of dereplicated, novel actinomycetes isolated from marine sediments. The success of the strategy is exemplified by the discovery of a range of novel bioactive compounds, notably atrop-abyssomicin C and proximicins A, B and C from Verrucosispora strains isolated from sediment samples taken from the Sea of Japan and the Raune Fjord, respectively, and the dermacozines derived from Dermacoccus strains isolated from the Challenger Deep of the Mariana Trench in the Pacific Ocean. The importance of current advances in prokaryotic systematics in work of this nature is stressed and a plea made that resources be sought to train, support and employ the next generation of actinobacterial systematists. PMID- 20582472 TI - Drug related problems after discharge from an Australian teaching hospital. AB - OBJECTIVE: To reconcile patients' medicines and to classify drug related problems identified during medication review conducted after discharge from hospital. SETTING: Patients were discharged from the cardiology unit of Westmead Hospital after recruitment into the Westmead Medicines Project which ran from 2004 to 2007. METHOD: This retrospective study involved an analysis of drugs, diseases and drug related problems in medication review reports available for 76 out of 85 patients who received a Home Medicines Review (HMR). Data sources for medication reconciliation and analyses also included hospital discharge summaries (n = 70) and GP referrals for HMR (n = 44). Comprehensive clinical profiles were constructed for the 76 subjects whose drug related problems were identified, coded, and then classified from their HMR reports. MAIN OUTCOME MEASURES: Number, type, distribution and international classification of drugs, diseases and drug related problems. RESULTS: Patients were prescribed drugs for a broad range of cardiovascular, circulatory, endocrine, respiratory and digestive system diseases. Mean number of drugs per patient in discharge summaries: 8.7 +/- SD 3.3 (range 3-19); in GP referrals: 8.9 +/- SD 4.3 (range 2-23); and in HMR reports: 10.8 +/- SD 4.0 (range 3-24). Mean number of diseases per patient in discharge summaries: 4.1 +/- SD 2.9 (range 1-11); and in HMR reports: 4.7 +/- SD 2.6 (range 1-12). A total of 398 drug related problems were identified for 71 (93.3%) patients with mean 5.6 +/- SD 4.3 problems (range 1-21). The most frequently recorded problems were the patients' uncertainty about drug aim: n = 128 (32.0%); potential interactions n = 89 (22.4%); and adverse reactions n = 60 (15.1%). CONCLUSION: This study showed that patients recently discharged from a tertiary care hospital had a significant number of drug related problems. Classification of drugs and diseases revealed a broad range of non-cardiovascular medicines and conditions in the patients from an acute care cardiology unit. We found that home medicines review provided continuity of care and an opportunity for medication reconciliation which revealed marked differences in number of drugs, between hospital discharge and medicines review. The patients' uncertainly about their drugs and their diverse range of co-morbidities indicated the need for timely counselling by pharmacists in the community. PMID- 20582473 TI - Microalgal biomass production: challenges and realities. AB - The maximum quantum yield (Phi (max)), calculated from the maximum chlorophyll a specific photosynthetic rate divided by the quantum absorption per unit chlorophyll a, is 8 photons or 0.125 mol C per mol Quanta light energy. For the average solar radiation that reaches the earth's surface this relates to a photosynthetic yield of 1.79 g(dw) m(-2) day(-1) per percentage photosynthetic efficiency and it could be doubled for sunny, dry and hot areas. Many factors determine volumetric yields of mass algal cultures and it is not simply a question of extrapolating controlled laboratory rates to large scale outdoor production systems. This is an obvious mistake many algal biotechnology start-up companies make. Closed photobioreactors should be able to outperform open raceway pond cultures because of the synergistic enhancement of a reduced boundary layer and short light/dark fluctuations at high turbulences. However, this has not been shown on any large scale and to date the industrial norm for very large production systems is open raceway production ponds. Microalgal biomass production offers real opportunities for addressing issues such as CO(2) sequestration, biofuel production and wastewater treatment, and it should be the preferred research emphasis. PMID- 20582475 TI - Anisotropic solute diffusion tensor in porcine TMJ discs measured by FRAP with spatial Fourier analysis. AB - A new method solely based on spatial Fourier analysis (SFA) was developed to completely determine a two-dimensional (2D) anisotropic diffusion tensor in fibrous tissues using fluorescence recovery after photobleaching (FRAP). The accuracy and robustness of this method was validated using computer-simulated FRAP experiments. This method was applied to determine the region-dependent anisotropic diffusion tensor in porcine temporomandibular joint (TMJ) discs. The average characteristic diffusivity of 4 kDa FITC-Dextran across the disc was 26.05 +/- 4.32 MUm2/s which is about 16% of its diffusivity in water. In the anteroposterior direction, the anterior region (30.99 +/- 5.93 MUm2/s) had significantly higher characteristic diffusivity than the intermediate region (20.49 +/- 5.38 MUm2/s) and posterior region (20.97 +/- 2.46 MUm2/s). The ratio of the two principal diffusivities represents the anisotropy of the diffusion and ranged between 0.45 and 0.51 (1.0 = isotropic). Our results indicated that the solute diffusion in TMJ discs is inhomogeneous and anisotropic. These findings suggested that diffusive transport in the TMJ disc is dependent on tissue composition (e.g., water content) and structure (e.g., collagen orientation). This study provides a new method to quantitatively investigate the relationship between solute transport properties and tissue composition and structure. PMID- 20582476 TI - Stiffness analysis of cardiac electrophysiological models. AB - The electrophysiology in a cardiac cell can be modeled as a system of ordinary differential equations (ODEs). The efficient solution of these systems is important because they must be solved many times as sub-problems of tissue- or organ-level simulations of cardiac electrophysiology. The wide variety of existing cardiac cell models encompasses many different properties, including the complexity of the model and the degree of stiffness. Accordingly, no single numerical method can be expected to be the most efficient for every model. In this article, we study the stiffness properties of a range of cardiac cell models and discuss the implications for their numerical solution. This analysis allows us to select or design numerical methods that are highly effective for a given model and hence outperform commonly used methods. PMID- 20582477 TI - Histone deacetylase inhibitors synergistically potentiate death receptor 4 mediated apoptotic cell death of human T-cell acute lymphoblastic leukemia cells. AB - Cell-death signaling through the pro-apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors, death receptor 4 (DR4) and DR5, has shown tumor-selective apoptotic activity. Here, we examine susceptibility of various leukemia cell lines (HL-60, U937, K562, CCRF-CEM, CEM-CM3, and THP-1) to an anti-DR4 agonistic monoclonal antibody (mAb), AY4, in comparison with TRAIL. While most of the leukemia cell lines were intrinsically resistant to AY4 or TRAIL alone, the two T-cell acute lymphoblastic leukemia (T-ALL) lines, CEM-CM3 and CCRF-CEM cells, underwent synergistic caspase-dependent apoptotic cell death by combination of AY4 or TRAIL with a histone deacetylase inhibitor (HDACI), either suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). All of the combined treatments synergistically downregulated several anti-apoptotic proteins (c-FLIP, Bcl-2, Bcl-X(L), XIAP, and survivin) without significant changing the expression levels of pro-apoptotic proteins (Bax and Bak) or the receptors (DR4 and DR5). Downregulation of c-FLIP to activate caspase-8 was a critical step for the synergistic apoptosis through both extrinsic and intrinsic apoptotic pathways. Our results demonstrate that the HDACIs have synergistic effects on DR4 specific mAb AY4-mediated cell death in the T-ALL cells with comparable competence to those exerted by TRAIL, providing a new strategy for the targeted treatment of human T-ALL cells. PMID- 20582474 TI - Etioplast and etio-chloroplast formation under natural conditions: the dark side of chlorophyll biosynthesis in angiosperms. AB - Chloroplast development is usually regarded as proceeding from proplastids. However, direct or indirect conversion pathways have been described in the literature, the latter involving the etioplast or the etio-chloroplast stages. Etioplasts are characterized by the absence of chlorophylls (Chl-s) and the presence of a unique inner membrane network, the prolamellar body (PLB), whereas etio-chloroplasts contain Chl-s and small PLBs interconnected with chloroplast thylakoids. As etioplast development requires growth in darkness for several days, this stage is generally regarded as a nonnatural pathway of chloroplast development occurring only under laboratory conditions. In this article, we have reviewed the data in favor of the involvement of etioplasts and etio-chloroplasts as intermediary stage(s) in chloroplast formation under natural conditions, the molecular aspects of PLB formation and we propose a dynamic model for its regulation. PMID- 20582478 TI - Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis. PMID- 20582479 TI - In reply to: Association between utility and treatment among patients with prostate cancer. AB - This is a brief commentary in response to article-Jayadevappa et al. (Qual Life Res 19:711-729, 2010). The commentary draws attention to issues that complicate QoL assessments in generic and disease-specific measures and its association to the treatment. PMID- 20582480 TI - Tissue allograft coding and traceability in USM Tissue Bank, Malaysia. AB - In Malaysia, tissue banking activities began in Universiti Sains Malaysia (USM) Tissue Bank in early 1990s. Since then a few other bone banks have been set up in other government hospitals and institutions. However, these banks are not governed by the national authority. In addition there is no requirement set by the national regulatory authority on coding and traceability for donated human tissues for transplantation. Hence, USM Tissue Bank has taken the initiatives to adopt a system that enables the traceability of tissues between the donor, the processed tissue and the recipient based on other international standards for tissue banks. The traceability trail has been effective and the bank is certified compliance to the international standard ISO 9001:2008. PMID- 20582481 TI - Amides, triterpene and flavonoids from the leaves of Melastoma malabathricum L. AB - Successive extraction of the dried leaves of Melastoma malabathricum, followed by purification using repeated chromatographic techniques, yielded six compounds, including two amides, auranamide and patriscabratine, a triterpene, alpha-amyrin, and three flavonoids, quercitrin, quercetin and kaempferol-3-O-(2'',6''-di-O-p trans-coumaroyl)-beta-glucoside. Their structures were elucidated by spectroscopic means and also by direct comparison of their spectroscopic data with respective published data. These three phenolic constituents were found to be active as free radical scavengers, with quercetin being the strongest radical scavenger, having an IC(50) value of 0.69 microM in the UV method. Quercitrin and kaempferol-3-O-(2'',6''-di-O-p-trans-coumaroyl)-beta-glucoside showed moderate radical scavenging, with IC(50) values of 74.1 and 108.8 microM, respectively. PMID- 20582482 TI - Study of intra-subject random variations of stabilometric parameters. AB - This study of intra-subject random variations of stabilometric parameters was achieved in the context of the standardized clinical stabilometry, in use in France and Southern Europe since 1985. The outstanding interest of stabilometry to follow up patients makes the results of this study indispensable for clinicians and their international publication is particularly important as, these days, the standardization Committee for clinical stabilometry resumes its work within the International Society for Postural and Gait Research. Such a study is possible only on the topological stabilometric parameters because of the stroboscopic effect on the dynamic parameters of the sampling rate of our computerized measuring chains. PMID- 20582483 TI - Improved breath alcohol analysis in patients with depressed consciousness. AB - Many patients in pre-hospital and emergency care are under the influence of alcohol. In addition, some of the more common pathological conditions can introduce a behaviour that can be mistaken to be related to alcohol inebriation. Fast quantitative determination of the breath alcohol concentration (BrAC) in emergency patients facilitates triage and medical assessment, but shallow expirations performed by non-cooperative patients reduce the measurement reliability. The aim of this study was to evaluate if breath alcohol analysis in non-cooperative patients can be improved with use of simultaneous measurement of the expired carbon dioxide (CO(2)). With prototypes of a handheld breath alcohol analyser based on infrared transmission spectroscopy the alcohol and CO(2) concentration in expired breath from 37 cooperative and non-cooperative patients were measured. The results show that enhanced breath sampling with use of a pump and estimation of the end expiratory BrAC with use of the ratio between the measured partial pressure of CO(2) (PCO2) and a reference value of the alveolar PCO2, provided adequate correlation with the blood alcohol concentration (BAC). This pre-clinical study has shown that breath alcohol analysis in shallow expirations from non-cooperative patients can be improved with use of CO(2) as a tracer gas. PMID- 20582484 TI - Advanced biofeedback from surface electromyography signals using fuzzy system. AB - The aims of this study were to develop a fuzzy inference-based biofeedback system and investigate its effects when inducing active (shoulder elevation) and passive (relax) pauses on the trapezius muscle electromyographic (EMG) activity during computer work. Surface EMG signals were recorded from clavicular, descending (bilateral) and ascending parts of the trapezius muscles during computer work. The fuzzy system readjusted itself based on the history of previous inputs. The effect of feedback was assessed in terms of muscle activation regularity and amplitude. Active pause resulted in non-uniform muscle activity changes in the trapezius muscle depicted by increase and decrease of permuted sample entropy in ascending and clavicular parts of trapezius, respectively (P < 0.05) compared with no pause. Concomitantly, the normalized root mean square of EMG increased approximately 5% in descending part of trapezius bilaterally (P < 0.01). These findings confirm that advanced feedback can change the pattern of muscle activation. PMID- 20582485 TI - Association between physician specialty and uptake of new medical technologies: HPV tests in Florida Medicaid. AB - BACKGROUND: It is well established that specialists often adopt new medical technologies earlier than generalists, and that racial and ethnic minority patients are less likely than White patients to receive many procedures and prescription drugs. However, little is known about the role that specialists or generalists may play in reducing racial and ethnic disparities in uptake of new medical technologies. Human papillomavirus (HPV) DNA tests, introduced as a cervical cancer screening tool in 2000, present a rich context for exploring patterns of use across patient and provider subgroups. OBJECTIVE: To identify patient characteristics and the provider specialty associated with overall and appropriate use of HPV DNA tests over time, and to examine the associations between clinical guidelines and adoption of the test in an underserved population. DESIGN: Retrospective longitudinal study using Florida Medicaid administrative claims data. PARTICIPANTS: Cervical cancer screening test claims for 415,239 female beneficiaries ages 21 to 64 from July 2001 through June 2006. MAIN MEASURES: Overall and appropriate use of HPV DNA tests. KEY RESULTS: Although minority women were initially less likely than White women to receive HPV DNA tests, test use grew more rapidly among Black and Hispanic women compared to White women. Obstetricians/gynecologists were significantly more likely than primary care providers to administer HPV DNA tests. Release of the first set of clinical guidelines was associated with a large increase in the use of HPV DNA tests (adjusted odds ratio: 2.46, p<0.0001); subsequent guidelines were associated with more modest increases. CONCLUSIONS: Uptake of new cervical cancer screening protocols can occur quickly among traditionally underserved groups and may be aided by early adoption by specialists. PMID- 20582486 TI - Cytochrome c oxidase is essential for copper-induced regression of cardiomyocyte hypertrophy. AB - Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy. PMID- 20582487 TI - Recent updates on the melanin-concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists. AB - Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic peptide which was originally found to lighten skin color in fish that is highly conserved among many species. MCH interacts with two G-protein-coupled receptors, MCH1R and MCH2R, but only MCH1R is expressed in rodents. MCH is mainly synthesized in the lateral hypothalamus and zona incerta, while MCH1R is widely expressed throughout the brain. Thus, MCH signaling is implicated in the regulation of many physiological functions. The identification of MCH1R has led to the development of small-molecule MCH1R antagonists that can block MCH signaling. MCH1R antagonists are useful not only for their potential therapeutic value, but also for understanding the physiological functions of the endogenous MCH system. Here, we review the physiological functions of the MCH system which have been investigated using MCH1R antagonists such as food intake, anxiety, depression, reward, and sleep. This will help us understand the physiological functions of the MCH system and suggest some of the potential applications of MCH1R antagonists in human disorders. PMID- 20582488 TI - Secretin mRNA in the subdivision of primary sensory neurons in the trigeminal ganglion of rats. AB - The primary sensory neurons use glutamate as a major neurotransmitter. Several neuropeptides are also found in these neurons. In our laboratory we demonstrated secretin-like immunoreactivity in primary sensory neurons of several species including human, rat and cat. In the present experiment utilizing in situ hybridization, we have demonstrated for the first time that secretin is not only immunostained but is also expressed in the primary sensory neurons of the trigeminal ganglion of male rats. In intact rats, secretin mRNA was not observed; we had to use intracerebroventricular colchicine administration to induce the expression of secretin. Secretin was expressed in about 5% of the cells in all the three subdivisions of the trigeminal ganglion. The secretin-synthetizing cells were large and medium sized, and their mean diameter was about 50 MUm. When we compared the percentage and the size of secretin to that of calcitonin gene related peptide (CGRP), substance-P (SP) and vasoactive intestinal polypeptide (VIP) cells, it was found that CGRP, SP and VIP are present in about 15-20% of the cells and their mean diameter is about 20-25 MUm. The morphometric data indicate that secretin is present in a subdivision of neurons that is different from the subdivision of the CGRP, SP and VIP cells. It is suggested that secretin may modulate the function of the primary neurotransmitter. PMID- 20582489 TI - Anatomical global spatial normalization. AB - Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain structures. Two types of mean preserving scaling methods were investigated, "shape preserving" and "shape standardizing". aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to rho (2), the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages. PMID- 20582490 TI - The role of lipid transfer proteins in allergic diseases. AB - Nonspecific lipid transfer proteins (LTPs) are important allergens in fruits, vegetables, nuts, pollen, and latex. Despite their wide distribution throughout the plant kingdom, their clinical relevance is largely confined to the Mediterranean area. As they can sensitize via the gastrointestinal tract, LPTs are considered true food allergens, and IgE reactivity to LTPs is often associated with severe systemic symptoms. Although Pru p 3 represents the predominant LTP in terms of patients' IgE recognition, the contribution of pollen LTPs in primary sensitization cannot be ruled out. Due to structural homology, LTPs from different allergen sources are generally IgE cross-reactive. However, sensitization profiles among allergic patients are extremely heterogeneous, and individual cross-reactivity patterns can be restricted to a single LTP or encompass many different LTPs. Molecule-based approaches in allergy research and diagnosis are important for better understanding of LTP allergy and could assist clinicians with providing adequate patient-tailored advice. PMID- 20582491 TI - Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs. AB - The aim of this study was to evaluate the healing of class III furcation defects following transplantation of autogenous periosteal cells combined with beta tricalcium phosphate (beta-TCP). Periosteal cells obtained from Beagle dogs' periosteum explant cultures, were inoculated onto the surface of beta-TCP. Class III furcation defects were created in the mandibular premolars. Three experimental groups were used to test the defects' healing: group A, beta-TCP seeded with periosteal cells were transplanted into the defects; group B, beta TCP alone was used for defect filling; and group C, the defect was without filling materials. Twelve weeks post surgery, the tissue samples were collected for histology, immunohistology and X-ray examination. It was found that both the length of newly formed periodontal ligament and the area of newly formed alveolar bone in group A, were significantly increased compared with both group B and C. Furthermore, both the proportion of newly formed periodontal ligament and newly formed alveolar bone in group A were much higher than those of group B and C. The quantity of cementum and its percentage in the defects (group A) were also significantly higher than those of group C. These results indicate that autogenous periosteal cells combined with beta-TCP application can improve periodontal tissue regeneration in class III furcation defects. PMID- 20582492 TI - Percutaneous penetration modifiers and formulation effects: thermal and spectral analyses. AB - The study investigated the formulation effects of laurocapram and iminosulfurane derived penetration modifiers on human stratum corneum using thermal and spectral analyses. Firstly, formulations of penetration modifiers were assessed as enhancers/retardants using the model permeant, diethyl-m-toluamide followed by investigation of their mechanisms of action using differential scanning calorimetry (DSC) and attenuated total reflectance Fourier-transform infra-red spectroscopy. The penetration modifiers investigated were laurocapram, 3 dodecanoyloxazolidin-2-one (N-0915), S,S-dimethyl-N-(4-bromobenzoyl) iminosulfurane (DMBIS), S,S-dimethyl-N-(2-methoxycarbonylbenzenesulfonyl) iminosulfurane (DMMCBI) and tert-butyl 1-dodecyl-2-oxoazepan-3-yl-carbamate (TBDOC) that were formulated in either water, propylene glycol (PG), ethanol or polyethylene glycol 400 (PEG 400). The results explain the mechanism for the first time why an enhancer can become a retardant or vice versa depending upon the vehicle in which it is applied to the skin. DSC indicated that penetration modifier formulations enhanced permeation of active mainly by disruption and fluidization of the stratum corneum lipid bilayers while IR data indicated characteristic blue shifts with decreases in peak intensity. On the other hand, DSC of penetration modifier formulations showing retardation depicted elevated T (m2) with a strengthening of lipid-protein complex while IR results indicated formation of multiple peaks around 1,738 cm(-1) transition in stratum corneum spectra suggesting retardation may be caused by organization of SC lipids by increased H-bonding. PMID- 20582493 TI - Floating tablet of trimetazidine dihydrochloride: an approach for extended release with zero-order kinetics. AB - Trimetazidine dihydrochloride is an effective anti-anginal agent; however, it is freely soluble in water and suffers from a relatively short half-life. To solve this encumbrance, it is a prospective candidate for fabricating trimetazidine extended-release formulations. Trimetazidine extended-release floating tablets were prepared using different hydrophilic matrix forming polymers including HPMC 4000 cps, carbopol 971P, polycarbophil, and guar gum. The tablets were fabricated by dry coating technique. In vitro evaluation of the prepared tablets was performed by the determination of the hardness, friability, content uniformity, and weight variation. The floating lag time and floating duration were also evaluated. Release profile of the prepared tablets was performed and analyzed. Furthermore, a stability study of the floating tablets was carried out at three different temperatures over 12 weeks. Finally, in vivo bioavailability study was done on human volunteers. All tablet formulas achieved < 0.5 min of floating lag time, more than 12 h of floating duration, and extended t (1/2). The drug release in all formulas followed zero-order kinetics. T4 and T8 tablets contained the least polymer concentration and complied with the dissolution requirements for controlled-release dosage forms. These two formulas were selected for further stability studies. T8 exhibited longer expiration date and was chosen for in vivo studies. T8 floating tablets showed an improvement in the drug bioavailability compared to immediate-release tablets (Vastrel(r) 20 mg). PMID- 20582494 TI - The transdermal patches for site-specific delivery of letrozole: a new option for breast cancer therapy. AB - The aim of this work was to evaluate capability of site-specific delivery of a transdermal patch through determination of letrozole in local tissues disposition in female mice. After transdermal administration, the letrozole levels in skin, muscle, and plasma were 10.4-49.3 MUg/g, 1.64-6.89 MUg/g, and 0.35-1.64 MUg/mL, respectively. However, after the mice received letrozole suspension, the drug concentration of plasma and muscle were 0.20-4.80 MUg/mL and 0.15-2.38 MUg/g. There was even no drug determined in skin through all experiments. Compared with oral administration, the transdermal patch for site-specific delivery of letrozole could produce high drug concentrations in skin and muscle and meanwhile obtain low drug level in plasma. These findings show that letrozole transdermal patch is an appropriate delivery system for application to the breast tumor region for site-specific drug delivery to obtain a high local drug concentration and low circulating drug concentrations avoiding the risk of systemic side effects. PMID- 20582495 TI - The Chitranjan Ranawat Award: fate of two-stage reimplantation after failed irrigation and debridement for periprosthetic knee infection. AB - BACKGROUND: Irrigation and debridement is an attractive low morbidity solution for acute periprosthetic knee infection. However, the failure rate in the literature is high, averaging 68% (range, 61%-82%). Patients who fail subsequently undergo two-stage reimplantation after a prolonged period of illness. This leads to higher surgical risk and further delays in rehabilitation and may contribute to failure of subsequent revision surgery. QUESTIONS/PURPOSES: We determined the rerevision rate due to infection after two-stage reimplantation performed for failed irrigation and debridement of infected TKA. METHODS: We performed a multicenter retrospective review of periprosthetic knee infections treated with a two-stage procedure from 1994 to 2008. Selection criteria for the study included initial treatment with irrigation and debridement and subsequent two-stage revision surgery. Failure of two-stage revision was defined as the need for any additional surgery due to infection. RESULTS: Of the 83 knees that had undergone previous irrigation and debridement, 28 (34%) failed subsequent two stage revision and required reoperation for persistent infection. CONCLUSIONS: The failure rate in this series of two-stage revisions for periprosthetic knee infection in patients treated with previous irrigation and debridement is considerably higher than previously reported failure rates of two-stage revision. Factors affecting the failure rate may include host quality, thoroughness of debridement, and organism virulence. Patients and surgeons must understand that irrigation and debridement, while initially attractive, may lead to high failure rates of subsequent two-stage reimplantation. LEVEL OF EVIDENCE: Level III, therapeutic study. See the guidelines online for a complete description of level of evidence. PMID- 20582496 TI - Office-based core needle biopsy of bone and soft tissue malignancies: an accurate alternative to open biopsy with infrequent complications. AB - BACKGROUND: Biopsy is a critical step in the diagnosis of musculoskeletal malignancy. As an alternative to open biopsy, percutaneous core needle biopsy techniques have been developed. As many studies combine office-based, image guided, and operative biopsies, the accuracy of office-based core needle biopsy is not well documented. QUESTION/PURPOSES: We asked whether (1) office-based core needle biopsy for the diagnosis of malignant musculoskeletal neoplasms would have few complications and diagnostic and accuracy rates comparable to those cited in the literature for core needle biopsy, (2) diagnostic errors related to office based core needle biopsy would result in surgical treatment errors, and (3) tissue core quantity and tumor type would affect accuracy. PATIENTS AND METHODS: We retrospectively reviewed 234 patients with 252 core needle biopsies of malignant bone and soft tissue neoplasms at one institution between 1999 and 2007. Biopsy accuracy and errors were determined on the basis of histologic evaluation of prior or subsequent biopsies and/or resected specimens, when available. We eliminated 19 patients who had needle biopsies: three had the core needle biopsy completed in the operating room and 16 had insufficient documentation or followup, leaving 233 for study. RESULTS: Of the 233 core needle biopsies, 212 (91%) were diagnostic and accurate for malignancy. Fourteen (6%) biopsies were nondiagnostic. Major errors, defined as a benign diagnosis in a malignant tumor, occurred in seven cases (3%). Minor errors, defined as errors in histopathologic diagnosis or grade, occurred in 24 biopsies (10%). All nondiagnostic and major core needle biopsy errors were identified and addressed with either a diagnostic open biopsy or definitive wide local excision, resulting in no surgical treatment errors. Accuracy was not influenced by core number; however, myxoid lesions showed a correlation with biopsy error. There were no biopsy-related complications. CONCLUSIONS: Office-based core needle biopsy for diagnosis of malignant musculoskeletal neoplasms has high diagnostic and accuracy rates without associated complications. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of the level of evidence. PMID- 20582497 TI - How does osteonecrosis about the knee progress in young patients with leukemia?: a 2- to 7-year study. AB - BACKGROUND: Osteonecrosis is a major treatment complication of pediatric leukemias owing to its potential to cause joint deterioration. Because of potential long-term effects of osteonecrosis on joints, information regarding its progression and collapse in different patients can be used to identify high-risk groups, advise the patients and parents of this complication, and potentially consider the risk for development of osteonecrosis in planning primary treatment. QUESTIONS/PURPOSES: We therefore determined: (1) the incidence of joint collapse and/or pain in young patients with hematologic malignancies diagnosed with ON of the knee; (2) risk factors associated with collapse; and (3) the relationship between size and location of osteonecrotic knee lesions and the likelihood of joint collapse. PATIENTS AND METHODS: We retrospectively reviewed 109 patients with hematologic malignancies and MRI-confirmed knee osteonecrosis. The median age was 11.5 years (range, 2.3-18.8 years) at primary diagnosis of hematologic malignancy and a median age of 13.4 years (range, 2.7-23.3 years) at diagnosis of osteonecrosis of the knee. For analyses, we used the first and last MR images. Minimum clinical followup was 2.3 years after diagnosis of knee osteonecrosis (median, 6 years; range, 2.3-7.17 years). RESULTS: Joint collapse occurred in 22% (24 of 109). Older age, pain at osteonecrosis presentation, and lesions extending to the articular surface of distal femoral epiphyses were associated with joint collapse. CONCLUSIONS: Younger patients and those without extensive femoral epiphyseal involvement have a better prognosis for osteonecrosis of the knee. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 20582498 TI - [Characteristics of patients suffering from chronic pain with depressive symptoms in three different treatment settings]. AB - BACKGROUND: Only few studies considered demographic and medical characteristics of pain patients with depressive symptoms. METHODS: The present study is a cross sectional observation of 585 patients suffering from chronic pain and depressive symptoms from all over Switzerland who got an antidepressant treatment in 122 medical practices (internal medicine, general medicine, psychiatry). Based on their clinical experience within the Swiss mental health system, the authors hypothesized that internists and general practitioners, compared to psychiatrists, treat older and less depressive patients with less intense chronic pain and with regional origin from Central Europe. RESULTS: In accordance with this hypothesis, internists (and general practitioners), compared to psychiatrists, more frequently provided care for older patients from Central Europe with less severe depressive symptoms and lower pain intensity and less head pain. Furthermore, compared with Central European patients, those patients from Eastern and Southern Europe presented more intense overall pain mainly affecting the head, extremities, back, and thorax whereas Southern Europeans tended to suffer even more frequently from chest pain compared with their Central European peers. CONCLUSION: The study design pragmatically represents the caring situation for depressed patients with chronic pain in Switzerland regarding regional origin and pain intensity. The results are based on a respectable sample size recruited from all Swiss regions and by the physician specialities primarily involved in long-term management of this patient group. PMID- 20582499 TI - [Varicella and herpes zoster. Part 2: therapy and prevention]. AB - In Germany, five antiviral agents are approved for antiviral therapy in zoster patients (acyclovir, valacyclovir, famciclovir, brivudine, and foscarnet). They should be administered within 72 h after rash onset and can significantly shorten viral replication and reduce the complications. In 2004, the German Standing Committee on Vaccination (STIKO) at the Robert Koch Institute suggested the active immunization against varicella with a live attenuated varicella vaccine (Oka strain) for all children and young persons. The first dose is given between the ages of 11 and 14 months, the second at the earliest 4 weeks later. Passive immunization is indicated as postexposure prophylaxis in high-risk individuals within 72-96 h after exposure. High-risk individuals are pregnant women, immunocompromised patients, or newborns, whose mothers had a primary varicella infection 5 days before or 2 days after birth. The Shingles Prevention Study demonstrated that vaccination is the most effective strategy for prevention of herpes zoster and postherpetic neuralgia. PMID- 20582500 TI - [Interdisciplinary emergency admissions. Assurance of treatment quality and efficiency with an integrated treatment approach]. PMID- 20582501 TI - [Health services research in oncology using claims data]. AB - BACKGROUND: Cancer is in the focus of public and scientific interest as one of the leading causes of death, with an increasing case load due to demographic changes and rising treatment costs. Comparatively, little is known about health care utilization of cancer patients. METHODS: This article first gives an overview of health services research and claims data of German statutory health insurance funds. Second, claims data of the Gmunder ErsatzKasse (GEK) for a period of 3 months (10-12/2008) are used to analyze patterns of drug prescriptions by oncologists. RESULTS: A total of 1.98 million prescriptions were included. Based on all prescriptions, the proportion of compounded prescriptions is about 17 times higher for oncologists compared to other physicians (34.4% vs. 2.0%). Fur- thermore, the costs of these solutions prescribed by oncologists are higher (median: 397.68 Euros vs. 15.45 Euros). CONCLUSION: Health services research in oncology is urgently needed. Claims data of German health insurance funds offer a broad range of opportunities, especially when linked with other data. However, in the case of individually prepared solutions, claims data provide no further information on the drug. PMID- 20582502 TI - [Electrophysiologic diagnosis and therapy]. PMID- 20582503 TI - [Gallstone ileus in underlying stenosis of the sigmoid due to recurrent diverticulitis--a rare complication of cholelithiasis]. AB - BACKGROUND: Gallstone ileus is a rare complication of cholelithiasis and an uncommon cause of intestinal obstruction. It accounts for about 1-4% of all mechanical bowel obstructions. The clinical symptoms and signs of gallstone ileus are mostly nonspecific. CASE REPORT: An 82-year-old woman with recurrent diverticulitis of the sigmoid was admitted because of cramping right upper abdominal pain and signs of large bowel obstruction. Abdominal ultrasound revealed pneumobilia and severe diverticulitis of the sigmoid with signs of ileus. Endoscopic retrograde cholangiography visualized the cholecystoenteric fistula. In addition, computed tomography (CT) scan revealed two stones 3 cm in diameter leading to nearly complete obstruction of the sigmoid. The patient underwent an open cholecystectomy, closure of the cholecystoenteric fistula, and sigmoidectomy. CONCLUSION: This case report demonstrates that relative stenoses of the sigmoid due to recurrent diverticulitis may predispose to the impaction of foreign bodies. Gallstone ileus is a rare but important differential diagnosis of intestinal obstruction. Ultrasound and CT scans are very helpful in diagnosing gallstone ileus. The treatment is surgical. Unfortunately, surgical therapy of this rare complication is associated with a high morbidity and mortality rate due to multiple comorbidities and age-related problems of these patients. The management of patients with gallstone ileus should be individualized. PMID- 20582504 TI - [Symptomatic pericardial cyst]. PMID- 20582505 TI - [Not Available]. PMID- 20582507 TI - Disaster response. Natural disaster: Katrina. AB - The aftermath and response to a disaster can be divided into four phases. The importance of each depends on the length of time without resupply and the resources that are required. This in turn depends on the time span of the disaster; the area involved; the number of the population affected; the resupply available; the extent of the devastation; and the size of the evacuation. The above phases are discussed using hurricane Katrina as an example. The phases are as follows: immediate response, evacuation, backfill and resupply, and restoration. The restoration phase is usually the longest and requires the most resources. This article addresses the situation of Katrina, the mistakes that were made, the lessons that were learned, and the solutions that are needed. Appropriate training and practice are required for all participants using realistic scenarios. PMID- 20582508 TI - High-mobility-group box chromosomal protein 1 as a new target for modulating stress response. AB - Major surgical procedures induce a systemic inflammatory response syndrome (SIRS) characterized by the overproduction of proinflammatory cytokines, which induces excessive stress and may trigger postoperative complications. This has prompted the hypothesis that drugs which relieve SIRS might improve the postoperative course of major surgery. One of the most promising targets for these drugs is high-mobility-group box chromosomal protein 1 (HMGB1). In 1999, HMGB1 was found to be a key late mediator of sepsis. It is now known to be associated with various kinds of acute and chronic inflammation, and is recognized as one of the most important danger signals in stress response. In this article, we present the latest information about HMGB1 and discuss its promise as a novel target for modulating stress response. PMID- 20582509 TI - Aberrant methylation in non-small cell lung cancer. AB - The potential of tumor suppressor genes (TSGs) to serve as clinical markers for disease detection, progression, and therapeutic response was evaluated by conducting a comprehensive review of the English-language scientific literature on aberrant promoter methylation of TSGs in non-small cell lung cancer (NSCLC). Genome-wide hypermethylation and silencing of TSGs are common features of cancer cells. Aberrant promoter methylation has been found in NSCLC, and research is now focused on the identification of specific genes that exhibit differential expression levels based on the methylation state. Aberrant methylation in NSCLC is observed in the early development of cancer and can be detected in DNA circulating in the blood or isolated from sputum. Therefore, methylation assays offer the promise of a noninvasive test for detecting cancer. In addition, the identification of cancer-specific epigenetic changes may be useful for molecular classification and disease stratification. Hence, the detection of cancer specific methylation changes heralds an exciting new era in the diagnosis of cancer, its prognosis, and therapeutic responsiveness, and warrants further investigation in NSCLC. PMID- 20582510 TI - Properties and identification of cancer stem cells: a changing insight into intractable cancer. AB - Although the idea was originally proposed decades ago, it has recently emerged that cancer can arise from small cell populations that differ from other progenies. These populations have the ability not only to renew themselves, but also to give rise to diverse phenotypes through the process of differentiation. The result is the formation of clinically observed heterogeneous tumors. Because of their similarity to somatic stem cells, these small cell populations have been termed cancer stem cells (CSCs). The involvement of CSCs was demonstrated in leukemia and has since been noted in other solid tumors, such as brain, breast, and gastrointestinal cancers. We support the notion that a curative operation serves as the most beneficial means to make a prognosis of malignancies. However, currently, chemotherapy is another of the promising strategies for the successful treatment of some malignancies. It is thought, however, that CSCs play a role in resistance to anticancer therapy, thus leading to the occurrence of metastasis, a common characteristic of intractable tumors. As a result, the study of CSCs is expected to improve the effectiveness of current therapies and lead to the development of novel therapeutic approaches for such cancers in the future. PMID- 20582511 TI - A segmentectomy of the right upper lobe has an advantage over a right upper lobectomy regarding the preservation of the functional volume of the right middle lobe: analysis by perfusion single-photon emission computed tomography/computed tomography. AB - PURPOSE: To evaluate the advantages of a segmentectomy of the right upper lobe (RUL) over a right upper (RU) lobectomy regarding the preservation of the functional volume of the right middle lobe (RML), the postoperative forced expiratory volume in one second (FEV(1)) of the RML was compared between an RU lobectomy and an RUL segmentectomy, by using a coregistered perfusion single photon emission computed tomography and computed tomography (SPECT/CT). METHODS: The pulmonary function tests and perfusion SPECT/CT were conducted before and after surgery (RU lobectomy: 7; RUL segmentectomy: 13). The FEV(1) of the RML before and after surgery was calculated from the data of the pulmonary function test and SPECT/CT. RESULTS: In the RU lobectomy group, the percentage change of FEV(1) was 71% +/- 12%, which was significantly lower in comparison to 92% +/- 9% in the RUL segmentectomy group (P = 0.001). In the lobectomy group, the preoperative FEV(1) of the RML was 0.17 +/- 0.10 l, which decreased significantly to 0.06 +/- 0.06l after surgery (P = 0.009). In the segmentectomy group, FEV(1) of the RML before and after the surgery were 0.23 +/- 0.10 l and 0.20 +/- 0.111, of which the difference was not significant. CONCLUSION: An RUL segmentectomy has an advantage over an RU lobectomy regarding the preservation of pulmonary function, due to a greater preservation of not only the lung tissue, but also the FEV(1) of the RML. PMID- 20582512 TI - An assessment of surgery for portal hypertensive patients performed at a single community hospital. AB - PURPOSE: The outcomes of surgery for portal hypertensive patients at a single community hospital in the last two decades were retrospectively examined. METHODS: From June 1989 to March 2008, 13 of 848 (1.5%) portal hypertensive patients admitted and treated at the community hospital underwent surgery. The types of surgery performed were a distal splenorenal shunt for 2 patients, gastric devascularization and splenectomy for 8, laparoscopic gastric devascularization and splenectomy for 1, distal gastrectomy for 1, and splenectomy alone for 1. This study reviewed the postoperative records of the endoscopic findings and additional treatments, and the perioperative records. RESULTS: No patient had bleeding from esophagogastric varices during the 75-month mean follow-up period after surgery. Five patients had one or two series of endoscopic treatment for recurrent likely-to-bleed esophageal varices. One patient needed interventional radiology for recurrent gastric varices. No patients died due to upper gastrointestinal bleeding. The survival rates were 87.5% after 5 years and 46.9% after 10 years. CONCLUSIONS: Surgery for portal hypertensive patients performed at a single community hospital is still safe and effective, and has been adequately incorporated into the late treatment strategy for portal hypertensive patients. PMID- 20582514 TI - Can the physiologic ability and surgical stress (E-PASS) scoring system predict operative morbidity after distal pancreatectomy? AB - PURPOSE: Mortality rates after pancreatic resection are now lower than 5% in high volume centers; however, morbidity remains high. This stresses the importance of identifying accurate predictors of operative morbidity after pancreatic resection. The Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system was developed for a comparative audit of general surgical patients. Our previous study confirmed its usefulness for predicting morbidity after pancreaticoduodenectomy. In the present study, we evaluated whether the E PASS scoring system can predict the occurrence of complications after distal pancreatectomy (DP). METHODS: The subjects were 46 patients who underwent DP for pancreatic disease. We studied correlations between the incidence of postoperative complications and the preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS) of the E-PASS scoring system. RESULTS: A collective total of 20 postoperative complications developed in 13 (28.3%) of the 46 patients. All E-PASS scores, particularly PRS and CRS, were significantly higher in the patients with postoperative complications than in those without complications. The complication rate increased with increasing PRS, SSS, and CRS scores. CONCLUSION: The E-PASS scoring system is useful for predicting morbidity after DP. PMID- 20582513 TI - Impact of perioperative peripheral blood values on postoperative complications after esophageal surgery. AB - PURPOSE: Prediction of the postoperative course of esophagectomy is an important part of the strict perioperative management of patients undergoing surgery for esophageal cancer. METHODS: To evaluate their clinical importance, peripheral blood values, including white blood cell count (WBC), lymphocyte count, and the levels of total protein, transferrin, factor XIII, D-dimer, fibrin, and fibrinogen degradation products (FDP) were measured before and after esophagectomy for esophageal cancer in 24 patients. RESULTS: The preoperative WBC and the pre- and postoperative lymphocyte count were decreased remarkably in patients who received preoperative chemoradiotherapy. The values of perioperative serum transferrin were significantly lower in patients with postoperative pneumonia than in those without. The activity of plasma factor XIII was suppressed on postoperative day (POD) 7 in patients with pneumonia and on POD 14 in patients with leakage. CONCLUSIONS: These results suggest that patients who receive preoperative chemoradiotherapy are potentially immunosuppressed, the preoperative serum transferrin level is a possible predictive marker of postoperative pneumonia, and suppression of factor XIII activity is related to anastomotic insufficiency. PMID- 20582515 TI - Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria. AB - PURPOSE: Hepatectomy is feasible for patients with hepatocellular carcinoma (HCC) who are eligible for liver transplantation according to the Milan criteria if they have good hepatic function. This retrospective study investigates the prognostic factors of hepatectomy in HCC patients meeting the Milan criteria. METHODS: Between 1991 and 2005, 175 patients underwent hepatectomy for HCC at our institute; 111 met and 64 exceeded the Milan criteria. The prognostic factors for hepatectomy were investigated using a Cox regression model. RESULTS: Operative mortality and morbidity were significantly lower in the patients who met the criteria than in those who exceeded the criteria. After a median follow-up of 51.5 months, the 5-year survival rate was significantly better for the patients who met the criteria than for those who exceeded the criteria (77.8% vs 35.7%; P < 0.0001). The factors predictive of poor prognosis were poor differentiation, microscopic vasculobiliary invasion, and a high serum des-gamma-carboxy prothrombin (DCP) level (>100 mAU/ml) for the patients who met the Milan criteria; and only the presence of a microsatellite lesion for the patients who did not meet the Milan criteria. CONCLUSIONS: Hepatectomy is safe and beneficial for HCC patients who meet the Milan criteria, but a high preoperative serum DCP level may be predictive of a poor prognosis. PMID- 20582516 TI - Reconstruction of the knee extensor mechanism in patients with a malignant bone tumor of the proximal tibia. AB - PURPOSE: Reconstruction of the knee extensor mechanism after the excision of a malignant bone tumor is often difficult, particularly if the tumor is located in the proximal tibia. We developed a novel method to reconstruct the knee extensor mechanism using autologous fasciae, and subsequently evaluated the efficacy of this method. METHODS: We examined the studied reconstruction method, range of motion, extension lag, knee extensor strength, and functional evaluation of three patients with a malignant bone tumor in the proximal tibia. All three patients underwent reconstruction of the knee extensor mechanism by our method. RESULTS: All patients experienced satisfactory outcomes with regard to the above-mentioned parameters. The functional evaluation scores in the three patients were 90%, 95%, and 95% (mean, 90%). CONCLUSION: In this analysis of our recently devised reconstruction method, the follow-up duration was short and only three patients were investigated. However, if appropriate patients are carefully selected for this procedure, long-term outcomes associated with new technique may be better than those associated with other methods of the knee extensor reconstruction. PMID- 20582517 TI - Utilization of three-dimensional computed tomography for papillary thyroid carcinoma arising in the thyroglossal duct remnant: report of a case. AB - This report presents a rare and interesting case of papillary thyroid carcinoma arising in a thyroglossal duct remnant (TDR) that was diagnosed by three dimensional computed tomography (3DCT). The patient, a 61-year-old woman, presented with a painless mass in the anterior suprahyoid region that had gradually enlarged over a 2-year period. Three-dimensional CT successfully revealed the thyroglossal duct (TD) descending from the tumor to the isthmus of the thyroid. An ultrasonography-guided fine-needle aspiration biopsy of the tumor was positive for carcinoma. A total thyroidectomy was performed in addition to the Sistrunk procedure. The histological findings indicated papillary thyroid carcinoma arising in the TDR and thyroid papillary microcarcinoma in the left thyroid lobe. The patient underwent radioactive iodine ablation and thyroid suppression therapy. This is apparently the first reported case of papillary thyroid carcinoma arising in a TDR evaluated using 3DCT. Three-dimensional CT was able to clarify the relative locations of the tumor, TD, and thyroid in the present case, and visualization of the TD allowed a definitive preoperative diagnosis that would not otherwise have been possible using conventional imaging techniques. This case suggests that 3DCT may therefore play an important role in providing definitive information on patients with anterior neck masses that are difficult to diagnose. PMID- 20582518 TI - A rare primary diaphragmatic hemangioma successfully treated by laparoscopic surgery: report of a case. AB - This report presents a very rare case of a primary diaphragmatic hemangioma, which was successfully treated by laparoscopic surgery. A 64-year-old man with a left diaphragmatic mass without any significant symptoms was treated by laparoscopic surgery and thus was diagnosed to have a diaphragmatic hemangioma following a pathological examination. Laparoscopic treatment in the deep and narrow abdominal spaces such as the diaphragmatic region is very useful as a less invasive treatment, as well as providing an excellent observation from which to make an accurate diagnosis. PMID- 20582519 TI - Spontaneous left subclavian artery dissection with concurrent thrombosis and embolic occlusion of the lower limbs: report of a case. AB - A subclavian artery dissection (SAD) is usually associated with coexisting aortic disease, and spontaneous SAD is extremely rare. This report presents the case of a spontaneous SAD patient who developed atypical clinical symptoms. A 41-year-old woman presented with bilateral ischemia of her lower limbs. An urgent bilateral femoral thrombo-embolectomy was performed using a balloon catheter. Postoperative enhanced computed tomography (CT) demonstrated a localized thrombus in the left subclavian artery extending toward the descending thoracic aorta, and a follow-up CT angiogram obtained 3 months later revealed left SAD and complete resolution of the thrombus. The patient was anticoagulated with warfarin in addition to antiplatelet drugs after the balloon catheter thromboembolectomy. This is the first report of lower limb ischemia caused by an embolism from a mural thrombus of the descending thoracic aorta extending from spontaneous SAD. PMID- 20582520 TI - Malignant glomus tumor of the stomach with multiorgan metastases: report of a case. AB - This report presents the case of a 65-year-old female patient with a malignant glomus tumor of the stomach, with metastases to the kidney and brain. The clinical presentation and imaging results are discussed, and the literature on malignant glomus tumors is reviewed. PMID- 20582521 TI - Primary tuberculosis of the appendix in a young male patient: report of a case. AB - A 23-year-old man without a history of tuberculosis presented with right lower abdominal pain and a fever. An increased inflammatory response was found, and abdominal computed tomography showed a diffuse enlargement and wall thickening in the appendix. An ileocecal abscess and perforating appendicitis were suspected. Therefore, an emergency operation was performed. The surgery revealed a diffuse enlargement with adhesion to the retroperitoneum, which was suspected to be a neoplastic lesion of the appendix, thus an ileocecal resection including the appendix was performed. A histopathological examination revealed a number of epithelioid granulomas having Langerhans giant cells with caseous necrosis in the appendix, in addition to many granulomas without caseous necrosis in the regional lymph nodes. No tubercle bacilli were detected by Ziehl-Neelsen staining. Further examination revealed no tubercular lesions in other organs, thus leading to the diagnosis of primary tuberculosis of the appendix. This is an extremely rare disease reported in Japan. PMID- 20582522 TI - Rectal endometriosis masquerading as dissemination in a patient with rectal cancer: report of a case. AB - A 57-year-old woman was diagnosed as having rectal cancer. A barium enema study showed the apple-core sign at the rectosigmoid colon, and colonoscopy revealed an encircled ulcerated tumor. A laparoscope-assisted resection of the rectum was planned; however, the rectal cancer directly invaded the uterus body. The operation was converted to open surgery. An elastic hard tumor suspected of being peritoneal dissemination at the peritoneal reflection was detected and excised together with the rectum below the peritoneal reflection. A histological examination of this tumor revealed that cystic glands lined by nonmucinous columnar epithelial cells were seen on the serosal side and were embedded in the proper muscle of the rectum. This tumorous lesion was diagnosed as endometriosis. PMID- 20582523 TI - Fish bone penetration of the duodenum extending into the pancreas: report of a case. AB - We report a case of fish bone penetration of the duodenum extending into the pancreatic head, which was successfully treated by surgery. A 73-year-old woman was admitted with upper abdominal dull pain that had persisted for 3 days. Computed tomography showed a linear calcified body, which appeared to penetrate the posterior wall of the duodenal bulb into the pancreatic head. A laparotomy was performed based on the preoperative diagnosis of localized peritonitis caused by penetration of the duodenum into the pancreas by an ingested foreign body. The foreign body was safely removed from both the pancreas and duodenum and was found to be a fish bone, measuring 4 cm in length. Neither an abscess nor hematoma was detected at the site of the pancreatic head. The postoperative course was uneventful. This case demonstrates an unusual presentation of fish bone penetration of the duodenum with a migration to the pancreas. PMID- 20582524 TI - Long-term survival after a repetitive surgical approach in a patient with acinar cell carcinoma of the pancreas and recurrent liver metastases: report of a case. AB - Acinar cell carcinoma is a relatively rare malignant neoplasm, which represents 1%-2% of all pancreatic exocrine tumors. Its prognosis is thought to be poor, especially when it metastasizes to the liver. This report concerns a case of a long-term survivor of metastatic acinar cell carcinoma who was successfully treated with repetitive surgery. A 62-year-old man underwent a distal pancreatectomy for a pancreatic tumor, which was histologically diagnosed as an acinar cell carcinoma. The tumor recurred in the liver three times within 41 months. At the first recurrence, four hepatic lesions appeared 7 months after the initial pancreatectomy and were managed with an extended left hepatic lobectomy and partial liver resection. Thereafter, a solitary nodule in Segment 6 was identified 21 months after the second surgery and was treated with a partial liver resection. A solitary lesion in Segment 8/5 appeared 11 months after the third surgery and was also managed by a partial liver resection. The patient has remained disease-free for 22 months since the last surgery and has survived 65 months since the initial diagnosis. Although no consensus has been reached on surgery for metastatic acinar cell carcinoma, the current case has important implications for establishing an appropriate treatment strategy. PMID- 20582525 TI - Challenging surgical management of a giant inguinoscrotal hernia: report of a case. AB - This report describes the surgical management of a giant inguinoscrotal hernia, which extended below the patient's knees, causing considerable physical discomfort and impairment of his quality of life. Initial management involved improving the patient's general condition and performing progressive preoperative pneumoperitoneum over 18 days. Surgery involved debulking the contents of the massive hernia sac by performing right hemicolectomy and transverse colectomy, repositioning of the small bowel into the abdominal cavity, resection of the giant hernia sac, and plastic reconstruction of the penis and scrotal region. The abdominal wall was reinforced with composite mesh. Despite a complicated postoperative course, the patient recovered well and has progressively returned to normal activities. Although challenging and demanding, surgery represents the only mode of treatment that can offer the patient with a giant inguinoscrotal hernia a satisfactory level of function and quality of life. PMID- 20582526 TI - Digit-assisted thoracoscopic surgery for mediastinal tumors: a novel technique. AB - Digit-assisted thoracoscopic surgery (DATS) is a novel, minimally invasive approach for achieving a superior mediastinal mass, by allowing the surgeon's finger to pass into the superior mediastinum through a suprasternal route. In this study a DATS procedure for a bronchogenic cyst in the superior mediastinum was performed. The procedure worked well for dissecting the tissue around the mass, and thus reduced the effort required to perform the operation. In the current study DATS was found to be superior to the standard technique. PMID- 20582528 TI - Biofuels in China. AB - The Chinese government is stimulating the biofuels development to replace partially fossil fuels in the transport sector, which can enhance energy security, reduce greenhouse gas emissions, and stimulate rural development. Bioethanol, biodiesel, biobutanol, biogas, and biohydrogen are the main biofuels developed in China. In this chapter, we mainly present the current status of biofuel development in China, and illustrate the issues of feedstocks, food security and conversion processes. PMID- 20582527 TI - Past, present, and future industrial biotechnology in China. AB - Fossil resources, i.e. concentrated carbon from biomass, have been irrecoverably exhausted through modern industrial civilization in the last two hundred years. Serious consequences including crises in resources, environment and energy, as well as the pressing need for direct and indirect exploitation of solar energy, pose challenges to the science and technology community of today. Bioenergy, bulk chemicals, and biomaterials could be produced from renewable biomass in a biorefinery via biocatalysis. These sustainable industries will match the global mass cycle, creating a new form of civilization with new industries and agriculture driven by solar energy. Industrial biotechnology is the dynamo of a bioeconomy, leading to a new protocol for production of energy, bulk chemicals, and materials. This new mode of innovation will place the industry at center stage supported by universities and research institutes. Creativity in industrial biotechnology will be promoted and China will successfully follow the road to green modernization. China's rapid economic development and its traditional capacity in fermentation will place it in an advantageous position in the industrial biotechnology revolution. The development and current status of industrial biotechnology in China are summarized herein. PMID- 20582529 TI - Oxygen sensing: a common crossroad in cancer and neurodegeneration. AB - Prolyl hydroxylase domain (PHD) proteins are cellular oxygen sensors that orchestrate an adaptive response to hypoxia and oxidative stress, executed by hypoxia-inducible factors (HIFs). By increasing oxygen supply, reducing oxygen consumption, and reprogramming metabolism, the PHD/HIF pathway confers tolerance towards hypoxic and oxidative stress. This review discusses the involvement of the PHD/HIF response in two, at first sight, entirely distinct pathologies with opposite outcome, i.e. cancer leading to cellular growth and neurodegeneration resulting in cell death. However, these disorders share common mechanisms of sensing oxygen and oxidative stress. We will focus on how PHD/HIF signaling is pathogenetically implicated in metabolic and vessel alterations in these diseases and how manipulation of this pathway might offer novel treatment opportunities. PMID- 20582530 TI - The neurodevelopmental implications of PI3K signaling. AB - Our understanding of the mechanisms involved in the formation of the complex arrangement of neurons and their interconnections within the brain has made significant progress in recent years. Current research has uncovered a network of intracellular signaling events that provide precise coordination of a diverse array of cellular responses, including trafficking events, cytoskeletal remodeling, gene transcription, and protein ubiquitination and translation. This chapter considers the specific cellular responses controlled by the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is instructive with regard to a number of important steps involved in the development of the brain. These range from the mediation of extrinsic signals - such as growth factors, axon guidance cues, and extracellular matrix components - to intrinsic effectors, such as downstream signaling components that act, for example, at the translation level. PI3K signaling is, consequently, at the heart of controlling neuronal migration and neuronal morphogenesis, as well as dendrite and synapse development. Many neurobehavioral disorders arise as a consequence of subtle developmental abnormalities. Unsurprisingly, therefore, aberrant PI3K signaling has been indicated by many studies to be a contributing factor to the pathophysiology of disorders such as schizophrenia and autism. In this chapter, we will focus on the specific, yet divergent, cellular processes that are achieved through PI3K signaling in neurons and are key to brain development. PMID- 20582531 TI - Immunobiology of cancer therapies targeting CD137 and B7-H1/PD-1 cosignal pathways. AB - Cancer immunotherapy is finally entering a new era with manipulation of cosignaling pathways as a therapeutic approach, for which the principle was proved nearly two decades ago. In addition to CTLA-4, CD137 and B7-H1/PD-1 pathways are two new targets in the stage. CD137 pathway is costimulatory and its agonistic antibody delivers potent signal to drive T cell growth and activation. On the other hand, blockade of B7-H1/PD-1 pathway with antagonistic antibody has shown to protect ongoing T cell responses from impairment by immune evasion mechanism in cancer microenvironment. With these tools in hand, a mechanism-based design of combined immunotherapy with high efficacy is becoming a reality. PMID- 20582533 TI - Hypoxia and hypoxia inducible factors in cancer stem cell maintenance. AB - Hypoxia promotes tumor progression through multiple mechanisms including modifying angiogenesis, metabolism switch and invasion. Hypoxia inducible factors (HIFs), particularly HIF1alpha and HIF2alpha, are key mediators in cancer hypoxia response and high expression levels of HIFs correlate with a poor prognosis in various tumor types. Cancer stem cells (CSCs), also known as cancer initiating cells or tumor propagation cells, are neoplastic cells that could self-renewal, differentiate as well as initiate tumor growth in vivo. Cancer stem cells are believed to be the key drivers in tumor growth and therapy resistance. Hypoxia has been shown to help maintain multiple normal stem cell population but its roles in cancer stem cells were largely unknown. Our group and other researchers recently identified that hypoxia is also a critical microenvironmental factor in regulating cancer stem cells' self-renewal, partially by enhancing the activity of stem cell factors like Oct4, c-Myc and Nanog. The effects of hypoxia on cancer stem cells seem to be primarily mediated by HIFs, particularly HIF2alpha. HIF2alpha is highly expressed in cancer stem cells in gliomas and neuroblastomas and loss of HIF2alpha leads to significant decrease in cancer stem cell proliferation and self-renewal. These findings illustrated a new mechanism through which oxygen tension and microenvironment influences cancer development. Targeting hypoxia niches may therefore improve therapy efficacy by eliminating cancer stem cell population. PMID- 20582534 TI - From the bench to the bed side: PI3K pathway inhibitors in clinical development. AB - A number of intracellular kinase components of the PI3K/Akt/mTOR pathway have been targeted over the past few years, leading to a new generation of anticancer agents that effectively and specifically disrupt this pathway in tumor cells. Here, progress in the identification and clinical evaluation of compounds designed to modulate the enzymatic activity of PI3K, Akt, mTOR, and Hsp90 is reviewed. PMID- 20582532 TI - Phosphatidylinositol 3-kinase: the oncoprotein. AB - The catalytic and regulatory subunits of class I phosphoinositide 3-kinase (PI3K) have oncogenic potential. The catalytic subunit p110alpha and the regulatory subunit p85 undergo cancer-specific gain-of-function mutations that lead to enhanced enzymatic activity, ability to signal constitutively, and oncogenicity. The beta, gamma, and delta isoforms of p110 are cell-transforming as overexpressed wild-type proteins. Class I PI3Ks have the unique ability to generate phosphoinositide 3,4,5 trisphosphate (PIP(3)). Class II and class III PI3Ks lack this ability. Genetic and cell biological evidence suggests that PIP(3) is essential for PI3K-mediated oncogenicity, explaining why class II and class III enzymes have not been linked to cancer. Mutational analysis reveals the existence of at least two distinct molecular mechanisms for the gain of function seen with cancer-specific mutations in p110alpha; one causing independence from upstream receptor tyrosine kinases, the other inducing independence from Ras. An essential component of the oncogenic signal that is initiated by PI3K is the TOR (target of rapamycin) kinase. TOR is an integrator of growth and of metabolic inputs. In complex with the raptor protein (TORC1), it controls cap-dependent translation, and this function is essential for PI3K-initiated oncogenesis. PMID- 20582535 TI - Introduction. AB - The phosphoinositide-3-kinase (PI3K) family of lipid kinases has been well conserved from yeast to mammals. In this evolutionary perspective on the PI3K family, we discuss the prototypical properties of PI3Ks: 1) the utilization of sparse but specifically localized lipid substrates; 2) the nucleation signaling complexes at membrane-targeted sites; and 3) the integration of intracellular signaling with extracellular cues. Together, these three core properties serve to establish order within the entropic environment of the cell. Many human diseases, including cancer and diabetes, are the direct result of loss or defects in one or more of these core properties, putting much hope in the clinical use of PI3K inhibitors singly and in combination to restore order within diseased tissues. PMID- 20582537 TI - Imaging studies of recovery from unilateral neglect. AB - The paper reviews the contribution of functional neuroimaging investigations (using single photon emission tomography, positron emission tomography and functional magnetic resonance) to the study of the neural mechanisms of recovery in patients with unilateral spatial neglect due to stroke. In addition, it highlights the important contribution of Luigi Pizzamiglio's experimental work in establishing a theoretical framework for the interpretation of imaging findings. The main tenet of this conception is that the brain reorganisation associated to recovery results from the engagement of both ipsilesional and contralesional brain areas, which in normal subjects are associated to task-relevant processes, such as oculomotor behaviour and visuo-spatial attentional shifts. PMID- 20582536 TI - Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes. AB - AIMS/HYPOTHESIS: Upon stimulation of insulin signalling or contraction-induced AMP-activated protein kinase (AMPK) activation, the glucose transporter GLUT4 and the long-chain fatty acid (LCFA) transporter CD36 similarly translocate from intracellular compartments to the plasma membrane of cardiomyocytes to increase uptake of glucose and LCFA, respectively. This similarity in regulation of GLUT4 traffic and CD36 traffic suggests that the same families of trafficking proteins, including vesicle-associated membrane proteins (VAMPs), are involved in both processes. While several VAMPs have been implicated in GLUT4 traffic, nothing is known about the putative function of VAMPs in CD36 traffic. Therefore, we compared the involvement of the myocardially produced VAMP isoforms in insulin- or contraction-induced GLUT4 and CD36 translocation. METHODS: Five VAMP isoforms were silenced in HL-1 cardiomyocytes. The cells were treated with insulin or the contraction-like AMPK activator oligomycin or were electrically stimulated to contract. Subsequently, GLUT4 and CD36 translocation as well as substrate uptake were measured. RESULTS: Three VAMPs were demonstrated to be necessary for both GLUT4 and CD36 translocation, either specifically in insulin-treated cells (VAMP2, VAMP5) or in oligomycin/contraction-treated cells (VAMP3). In addition, there are VAMPs specifically involved in either GLUT4 traffic (VAMP7 mediates basal GLUT4 retention) or CD36 traffic (VAMP4 mediates insulin- and oligomycin/contraction-induced CD36 translocation). CONCLUSIONS/INTERPRETATION: The involvement of distinct VAMP isoforms in both GLUT4 and CD36 translocation indicates that CD36 translocation, just like GLUT4 translocation, is a vesicle mediated process dependent on soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex formation. The ability of other VAMPs to discriminate between GLUT4 and CD36 translocation allows the notion that myocardial substrate preference can be modulated by these VAMPs. PMID- 20582538 TI - Effect of retinal and/or extra-retinal information on age in memory-guided saccades. AB - The aim of the study was to determine whether the addition of retinal or extra retinal information could be used to improve memory-guided saccadic performance in healthy participants. Furthermore, we included two age groups in our study; healthy young adult subjects (mean age 20 years) and healthy middle-aged adult subjects (mean age 52 years). All subjects performed a novel task that incorporated a Go/NoGo task with a memory-guided saccade paradigm to investigate whether extra-retinal information (making a saccade towards the visible target) or retinal (a visible frame-of-reference) has any affect on the accuracy or variability of the response. We found all subjects made slight hypometric responses to the memory-guided targets. Both younger and middle-aged subjects revealed an increase in accuracy in the Go task compared with the NoGo task and the framed condition compared to the frameless condition, respectively. The frame also revealed a significant decrease in variability in the memory-guided saccades. A positive correlation in errors between the 1st and 2nd saccade in the Go task was revealed for all subjects; however, the older subjects revealed a greater correlation than younger subjects. The results presented indicate that younger and middle-aged perform highly similar patterns of errors during eye movements to remembered locations. However, middle-aged subjects show a greater tendency to use extra-retinal and retinal feedback to guide the response. PMID- 20582540 TI - Cervical spinal canal compromise in a 14-year-old girl with hereditary multiple exostoses. PMID- 20582541 TI - FDG-PET for early assessment of Alzheimer's disease: isn't the evidence base large enough? PMID- 20582542 TI - Preincisional versus postincisional administration of parecoxib in colorectal surgery: effect on postoperative pain control and cytokine response. A randomized clinical trial. AB - BACKGROUND: Preincisional pain management aims at reducing pain and inflammatory response. We investigated whether preincisional parecoxib administration reduces pain, opioid requirements, and cytokine production after surgery for colonic cancer. METHODS: Forty one patients whose American Society of Anesthesiologists (ASA) status was I-II and who were scheduled for colorectal cancer surgery were randomly divided in two groups according to the timing of parecoxib administration: Group PRE (preincisional) received parecoxib 40 mg intravenously 30 min before skin incision and group POST (postincisional) received the same dose 30 min after skin incision. Postoperative analgesia involved the administration of patient-controlled analgesia (PCA) morphine to all patients. We recorded verbal rating scale (VRS) scores and morphine consumption at 1, 6, 18, and 24 h after surgery and blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) 30 min before skin incision, at peritoneal closure, and 24 h postoperatively. RESULTS: The VRS scores were similar between groups. Although morphine consumption was significantly lower in group PRE at 6, 18 and 24 h postoperatively (p = 0.044, p = 0.02, p < 0.001, respectively) morphine-related adverse effects did not differ between the two groups. The serum IL-6 was significantly (p = 0.042) elevated from the baseline value 24 h postoperatively in group POST. CONCLUSIONS: Preincisional parecoxib administration compared to postincisional administration reduced postoperative morphine consumption, but without affecting morphine-related adverse effects and attenuated IL-6 production 24 h after surgery for colorectal cancer. PMID- 20582543 TI - Repeat resection of pulmonary metastasis is beneficial for patients with colorectal carcinoma. AB - BACKGROUND: The role for repeat pulmonary metastasectomy for colorectal carcinoma has not been well defined. To identify the class of patients who benefit from pulmonary resection of recurrent pulmonary metastases, we herein reviewed our institutional experience. METHODS: Between 1990 and 2007, 84 patients with pulmonary metastases from colorectal carcinomas underwent complete pulmonary resection, and 22 of them (26%) later underwent complete resection for repeat pulmonary metastasis. Various perioperative variables were investigated retrospectively in these patients to confirm a role for repeat metastasectomy and analyze prognostic factors after repeat pulmonary metastasectomy. RESULTS: Overall survival and disease-free survival after repeat pulmonary metastasectomy were, respectively, 61 and 32% at 5 years. On univariate analysis, male gender and less than 1 year of disease-free status after the first pulmonary metastasectomy demonstrated significantly adverse overall survival (p = 0.01 and p = 0.009, respectively). Elevated preoperative serum carcinoembryonic antigen (CEA) level and maximum tumor size larger than 3 cm were also significantly adverse prognostic factors for disease-free survival (p = 0.03 and p = 0.04, respectively). The overall survival curve after repeat pulmonary metastasectomy was almost identical with that after complete resection of the first pulmonary metastasis. CONCLUSIONS: Patients with more than 1 year of disease-free status after the first pulmonary metastasectomy demonstrated a significantly better overall survival. Normal preoperative serum CEA level and maximum tumor size <3 cm were significantly adverse prognostic factors for disease-free survival. Our data imply that repeat pulmonary metastasectomy might be beneficial as it can salvage a subset of patients with colorectal carcinoma who retain favorable prognostic determinants. PMID- 20582544 TI - Routine ultrasound and limited computed tomography for the diagnosis of acute appendicitis. AB - BACKGROUND: Acute appendicitis continues to be a challenging diagnosis. Preoperative radiological imaging using ultrasound (US) or computed tomography (CT) has gained popularity as it may offer a more accurate diagnosis than classic clinical evaluation. The optimal implementation of these diagnostic modalities has yet to be established. The aim of the present study was to investigate a diagnostic pathway that uses routine US, limited CT, and clinical re-evaluation for patients with acute appendicitis. METHODS: A prospective analysis was performed of all patients presenting with acute abdominal pain at the emergency department from June 2005 until July 2006 using a structured diagnosis and management flowchart. Daily practice was mimicked, while ensuring a valid assessment of clinical and radiological diagnostic accuracies and the effect they had on patient management. RESULTS: A total of 802 patients were included in this analysis. Additional radiological imaging was performed in 96.3% of patients with suspected appendicitis (n = 164). Use of CT was kept to a minimum (17.9%), with a US:CT ratio of approximately 6:1. Positive and negative predictive values for the clinical diagnosis of appendicitis were 63 and 98%, respectively; for US 94 and 97%, respectively; and for CT 100 and 100%, respectively. The negative appendicitis rate was 3.3%, the perforation rate was 23.5%, and the missed perforated appendicitis rate was 3.4%. No (diagnostic) laparoscopies were performed. CONCLUSIONS: A diagnostic pathway using routine US, limited CT, and clinical re-evaluation for patients with acute abdominal pain can provide excellent results for the diagnosis and treatment of appendicitis. PMID- 20582545 TI - Multidetector computed tomography with triple-bolus contrast medium administration protocol for preoperative anatomical and functional assessment of potential living renal donors. AB - OBJECTIVE: To evaluate multidetector computed tomography (MDCT) with a triple bolus contrast administration protocol for preoperative anatomical and functional assessment of living renal donors. METHODS: Fifty-five potential living renal donors underwent MDCT of which 27 proceeded to donor nephrectomy. A triple-bolus contrast administration protocol was used for simultaneous acquisition of arterial, nephrographic, and excretory phases. MDCT images were independently reviewed in random order by two radiologists blinded to surgical anatomy findings. Diagnostic accuracy for anatomical variants was quantified by sensitivity and specificity. Differential renal function (DRF) was derived from MDCT for 54 patients and compared with technetium-99 m dimercaptosuccinic acid renography (Tc-99 m DMSA). RESULTS: All triple-bolus MDCT examinations were technically adequate. Accessory renal arteries and veins were identified at surgery in 33% (n = 9/27) and 22% (n = 6/27) of donor kidneys. The mean difference between MDCT-derived DRF and DMSA was 0.8% (95% CI 0.1-1.6) with 95% limits of agreement of -4.6% (95% CI -3.3 to -5.9) to 6.3% (95% CI 5.0-7.6). MDCT delivered a mean (SD, range) radiation dose of 9.5 (3.6, 3.6-17.3) mSv. CONCLUSION: MDCT with a triple-bolus contrast administration provides accurate anatomical and functional evaluation of living renal donors. PMID- 20582546 TI - Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate. AB - INTRODUCTION: Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are controversial. The objective of this study was to investigate the impact of photodynamic diagnosis (PDD) on the recurrence-free survival rate of patients with the initial diagnosis of T1G3 bladder cancer. PATIENTS AND METHODS: Between 1995 and 2007, 153 patients were treated for T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition at our hospital, and 76 patients underwent TUR-BT in a standard white light setting at other institutions. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for induction of fluorescence. Average follow-up was 53.9 months. Fisher's exact test and Kaplan-Meier method were used to test data for significance. RESULTS: Of the 77 patients who were treated using PDD at initial TUR-BT, recurrence was observed in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed recurrence (P < 0.001). The detection rate of additional carcinoma in situ was 35.4% in the PDD group versus 21.8% in the white light group (P = 0.077). A limitation of the present study is the retrospective, monocentre setting, which is more likely to be biased. CONCLUSION: PDD during initial TUR-BT in T1G3 bladder cancer seems to reduce significantly the rate of recurrence in our study population. Therefore, PDD seems to be associated with superior initial tumour control and more effective tumour treatment even in patients with highly aggressive tumours like T1G3 bladder cancer. PMID- 20582547 TI - Prospective study of sexual dysfunction in men with rectal cancer: feasibility and results of nerve sparing surgery. AB - PURPOSE: Rectal cancer surgery is impaired by a high rate of postoperative sexual dysfunction cause of frequent nerve injuries. The aim of this study was to prospectively evaluate sexual function in a group of male patients after total mesorectal excision (TME) for rectal cancer, using an autonomic nerve sparing technique. METHODS: All patients underwent autonomic nerve preserving TME. Sexual function was assessed using the International Index of Erectile Function standardized questionnaire. All patients were studied preoperatively and at 3, 6, 12, 18, and 24 months after surgery. RESULTS: Fifty-one patients with adenocarcinoma of the rectum were enrolled; after excluding 16 patients not sexually active, nine with T4 stage disease and six with metastatic disease, 20 patients were prospectively evaluated. The preoperative erectile function (EF) domain score of the International Index of Erectile Function was 24.3 (+/-4.1). The score of the EF domain was 17.6 (+/-7.5), 19.l9 (+/-7.2), 20.3 (+/-7.4), 20.5 (+/-7.4), and 20.6 (+/-7.4) at 3, 6, 12, 18, and 24 months after surgery. In the group of patients in which there were no macroscopic damages to the nerves, only two out of 15 (13.3%) developed erectile dysfunction. All five patients in whom incomplete pelvic nerve preservation was necessary developed erectile dysfunction. CONCLUSION: Our data show that nerve sparing technique can reduce the incidence of sexual dysfunction. Unfortunately, the technique is not applicable in every patient. Indications and techniques of autonomic nerve preservation are not standardized. Controlled trials with long-term follow-up seem to be necessary. PMID- 20582548 TI - Transient evoked otoacoustic emissions in superior canal dehiscence syndrome. AB - Superior semicircular canal dehiscence syndrome (SCDS) is a clinical disorder that is characterized by vertigo and oscillopsia induced by loud sounds. Transient evoked otoacoustic emissions (TEOAEs) allow to noninvasively check the integrity of the cochlea. The present study aimed at identifying cochlear stress as the result of micro alterations of the cochlear functionality due to anatomic anomaly. 11 SCDS and 10 normal individuals as control group were submitted to history taking, otological examination, basic audiologic evaluation and TEOAEs analysis using the standard wideband protocol and moving time window analysis. Although TEOAEs test results showed no statistically significant difference using the standard protocol, off-line analysis of the waveforms' "effective duration" was statistically significantly shortened (p < 0.0001) when compared to normal ears. In conclusion, dehiscence of bone overlying the superior canal has been shown to have effects on inner ear function in terms of a third mobile window theory, thus altering pressure across cochlear partition with decrease in inner ear impedance. PMID- 20582549 TI - Functional outcomes of patients with advanced pyriform sinus cancer treated with extended near-total laryngopharyngectomy and free fasciocutaneous flap reconstruction. AB - The objective of this study was to evaluate the functional results in patients with advanced pyriform sinus cancer treated with extended near-total laryngopharyngectomy (ENTLP) and free fasciocutaneous flap reconstruction. We reviewed the medical records of patients with pyriform sinus cancer who were treated at Kaohsiung Chang Gung Memorial Hospital, a tertiary medical center in Taiwan, between June 1998 and December 2008. This retrospective study enrolled the patients who had a stage III or IV pyriform sinus cancer and was surgically treated with ENTLP and free fasciocutaneous flap reconstruction. Thirteen patients meeting the inclusion criteria were enrolled. Three patients had stage III cancer, and ten had IVa. All were men with the age distribution ranged from 38 to 75 years. The average length of hospitalization was 19 days. Twelve (92.3%) patients could develop shunt speech postoperatively, and eight (61.5%) patients used shunt speech for their routine conversation. Eleven (84.6%) patients could ultimately return to an oral diet; the remaining two (15.4%) patients stayed dependent on a feeding tube for part or all of their nutrition. Two patients died from distant metastases, and one patient died from complications of postoperative concurrent chemoradiotherapy, while the other ten patients survived until the last follow-up without evidence of locoregional tumor recurrence. In conclusion, in the surgical treatment of patients with locally advanced pyriform sinus cancer, ENTLP and free fasciocutaneous flap reconstruction is an oncologically safe, voice-conserving, and prosthesis-free procedure which offers satisfactory functional speech and swallowing outcomes. PMID- 20582550 TI - Respiratory complications after supracricoid partial laryngectomy. AB - The objective of the study was to analyze the incidence, treatment, and prevention of early and late respiratory complications in a series of patients who had supracricoid partial laryngectomies with either cricohyoidoepiglottopexy or cricohyoidopexy. From medical charts, we retrospectively reviewed 101 patients who underwent supracricoid partial laryngectomies, from 1980 to 2006, for laryngeal squamous cell carcinoma, and recorded the various postoperative complications and the time of decannulation. The mortality rate was 3.96%. Early complications included broncho-pulmonary infections and laryngeal stenoses which occurred in 9.9%. Univariate analysis showed a statistically significant relationship between the pulmonary complications and neck dissections (p < 0.04). Later, they were due to laryngeal obstruction (neolaryngeal mucosal flap, residual false vocal cord fold or arytenoid edema). The median decannulation time was 8 days, and there was a significant relationship between the decannulation delay and the pulmonary complications. Only two patients had a later definitive tracheotomy. Respiratory complications after supracricoid partial laryngectomy are frequent, but can be easily managed in most cases. A preoperative pulmonary assessment is necessary to select patients. During surgery, a precise impaction of the hyoid bone with the cricoid cartilage and a repositioning of an arytenoid can avoid some postoperative stenoses. PMID- 20582551 TI - Synergistic interaction effect between job control and social support at work on general psychological distress. AB - PURPOSE: Little is known about the interaction between job control and social support at work on common mental disorders. To examine whether there is a synergistic interaction effect between job control and social support at work on general psychological distress and whether it differs by the level of job demands. METHODS: About 1,940 male and female workers from the Malmo Shoulder and Neck Study were chosen for this cross-sectional study. Job control, social support at work, and job demands were measured by the Swedish version of the Job Content Questionnaire, and general psychological distress was assessed by the General Health Questionnaire. RESULTS: A significant excessive risk increase for general psychological distress was observed when workers had both low job control and low social support at work in both men and women. The synergistic effect was stronger in women, when job demands were low (Rothman's synergy index was 2.16 vs. 1.51 when job demands were high). However, in male workers, while a strong synergistic effect between job control and social support at work was found when job demands were low (synergy index was 9.25), there was an antagonistic effect when job demands were high (synergy index was 0.52). CONCLUSIONS: There was a synergistic interaction effect between job control and social support at work on general psychological distress, but the synergistic effect or its effect size differed by the level of job demands and gender. An atomic, additive approach to the risk assessment of the psychosocial work characteristics on common mental disorders could be misleading or lead to a risk underestimation. PMID- 20582552 TI - Reciprocal correlation between the expression of cyclooxygenase-2 and E-cadherin in human bladder transitional cell carcinomas. AB - Carcinoma cells become more motile and invasive via downmodulation of E-cadherin. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis. The aim of this study is to investigate the relationship between the expression of COX-2 and E-cadherin in a bladder cancer cell line and human bladder transitional cell carcinoma (TCCs). Phorbol 12-myristate 13-acetate (PMA) treatment for 5637 bladder cancer cells increased COX-2 expression, slightly induced Slug expression, and decreased E-cadherin expression. Ectopic expression of COX-2 or prostaglandin E(2) (PGE(2)) treatment for 5637 cells reduced E cadherin expression. This finding was confirmed by the result that knockdown of COX-2 expression or indomethacin administration increased the expression of E cadherin. When compared with cells' motility in serum-free medium, the treatment of PMA and PGE(2) increased cell motility, and indomethacin treatment slightly decreased cell motility. In the tissues of bladder TCCs, COX-2 expression was inversely correlated with membranous E-cadherin expression and positively correlated with nuclear beta-catenin expression. The expression of COX-2 and nuclear beta-catenin expression was significantly higher in TCCs of high grade and invasive growth than in TCCs of low grade and noninvasive growth. In contrast, membranous E-cadherin expression was more decreased in tumors of high grade and invasive growth. In addition, nuclear beta-catenin expression was significantly related to tumor recurrence. We suggest that COX-2 pathway reduces membranous E-cadherin expression in bladder TCCs and their expression pattern may provide important information in predicting the clinical behavior of bladder TCCs. PMID- 20582553 TI - Pseudopod-like basal cell processes in intestinal cholecystokinin cells. AB - Cholecystokinin (CCK) is secreted by neuroendocrine cells comprising 0.1%-0.5% of the mucosal cells in the upper small intestine. Using CCK promoter-driven green fluorescent protein (GFP) expression in transgenic mice, we have applied immunofluorescence techniques to analyze the morphology of CCK cells. GFP and CCK colocalize in neuroendocrine cells with little aberrant GFP expression. CCK containing cells are either flask- or spindle-shaped, and in some cells, we have found dendritic processes similar to pseudopods demonstrated for gut somatostatin containing D cells. Most pseudopods are short, the longest process visualized extending across three cells. Pseudopods usually extend to adjacent cells but some weave between neighboring cells. Dual processes have also been observed. Three-dimensional reconstructions suggest that processes are not unidirectional and thus are unlikely to be involved in migration of CCK cells from the crypt up the villus. Abundant CCK immunostaining is present in the pseudopods, suggesting that they release CCK onto the target cell. In order to identify the type of cells being targeted, we have co-stained sections with antibodies to chromogranin A, trefoil factor-3, and sucrase-isomaltase. CCK cell processes almost exclusively extend to sucrase-isomaltase-positive enterocytes. Thus, CCK cells have cellular processes possibly involved in paracrine secretion. PMID- 20582555 TI - Dural tears in percutaneous endoscopic lumbar discectomy. AB - The objective of the study was to demonstrate the clinical characteristics of dural tears during percutaneous endoscopic lumbar discectomy (PELD) and to discuss how to prevent this unintended complication. The study used data from 816 consecutive patients who underwent PELD between 2003 and 2007. A total of nine patients (1.1%) experienced symptomatic dural tears. The clinical outcomes were evaluated using the visual analogue scale (VAS), the Oswestry disability index (ODI), and modified MacNab criteria. Intractable radicular pain was the most common symptom, while classical manifestations, such as CSF leakage or wound swelling, were rare. In three of the nine cases, the dural tears were detected intraoperatively, while the remaining six cases were not recognized during the procedure. Among the unrecognized patients, two patients were found with nerve root herniation causing profound neurological deficits. All patients were managed by secondary open repair surgeries. The mean follow-up period was 30.8 months. The mean VAS of radicular leg pain improved from 8.3 to 2.6, and that of back pain improved from 4.1 to 2.6. The mean ODI improved from 69.6 to 29.2%. The final outcomes were excellent in one, good in five, fair in one, and poor in two patients. As application of the endoscopic procedure has been broadened to more complex cases, the risk of dural tears may increase. Unrecognized dural tear with nerve root herniation may cause permanent neurological sequelae. Accurate information and proper technical considerations are essential to prevent this unpredictable complication. PMID- 20582554 TI - Perioperative complications with rhBMP-2 in transforaminal lumbar interbody fusion. AB - Bone morphogenetic protein (BMP) is commonly used as an ICBG substitute for transforaminal lumbar interbody spine fusion (TLIF). However, multiple recent reports have raised concerns regarding a substantial incidence of perioperative radiculopathy. Also, given the serious complications reported with anterior cervical BMP use, risks related to swelling and edema with TLIF need to be clarified. As TLIF related complications with rhBMP-2 have generally been reported in small series or isolated cases, without a clear denominator, actual complication rates are largely unknown. The purpose this study is to characterize perioperative complications and complication rates in a large consecutive series of TLIF procedures with rhBMP-2. We reviewed inpatient and outpatient medical records for a consecutive series of 204 patients [113 females, 91 males, mean age 49.3 (22-79) years] who underwent TLIF using rhBMP-2 between 2003 and 2007. Complications observed within a 3-month perioperative interval were categorized as to etiology and severity. Wound problems were delineated as wound infection, hematoma/seroma or persistent drainage/superficial dehiscence. Neurologic deficits and radiculopathies were analyzed to determine the presence of a clear etiology (screw misplacement) and identify any potential relationship to rhBMP-2 usage. Complications were observed in 47 of 204 patients (21.6%) during the 3 month perioperative period. Major complications occurred in 13 patients (6.4%) and minor complications in 34 patients (16.7%). New or more severe postoperative neurologic complaints were noted in 13 patients (6.4%), 6 of whom required additional surgery. These cases included one malpositioned pedicle screw and one epidural hematoma. In four patients (2.0%), localized seroma/hematoma in the area of the foramen caused neural compression, and required revision. In one additional patient, vertebral osteolysis caused foraminal narrowing and radiculopathy, but resolved without further surgery. Persistent radiculopathy without clear etiology on imaging studies was seen in six patients. Wound related problems were seen in six patients (2.9%), distributed as wound infection (3), hematoma/seroma (1) and persistent drainage/dehiscence (2). Overall, this study demonstrates a modest complication rate for TLIF using rhBMP-2. While perioperative complications which appeared specific to BMP usage were noted, they occurred infrequently. It will be necessary to weigh this incidence of complications against the complication rate associated with ICBG harvest and any differential benefit in obtaining a solid arthrodesis. PMID- 20582556 TI - Preferential superior surface motion in wear simulations of the Charite total disc replacement. AB - Laboratory wear simulations of the dual-bearing surface Charite total disc replacement (TDR) are complicated by the non-specificity of the device's center of rotation (CoR). Previous studies have suggested that articulation of the Charite preferentially occurs at the superior-bearing surface, although it is not clear how sensitive this phenomenon is to lubrication conditions or CoR location. In this study, a computational wear model is used to study the articulation kinematics and wear of the Charite TDR. Implant wear was found to be insensitive to the CoR location, although seemingly non-physiologic endplate motion can result. Articulation and wear were biased significantly to the superior-bearing surface, even in the presence of significant perturbations of loading and friction. The computational wear model provides novel insight into the mechanics and wear of the Charite TDR, allowing for better interpretation of in vivo results, and giving useful insight for designing future laboratory physical tests. PMID- 20582557 TI - Low back pain in childhood and adolescence: assessment of sports activities. AB - A cross-sectional study that targeted a total of 43,630 pupils in Niigata City, Japan was performed. The objective of the study was to evaluate the association between sports activities and low back pain (LBP) in childhood and adolescence in Japan. Regarding risk factors of LBP, a large number of studies have been conducted that have examined gender differences, height and weight, body mass index, sports time, differences in lifestyle, family history, and mental factors; however, no definitive conclusion has yet been made. A questionnaire survey was conducted using 43,630 pupils, including all elementary school pupils from the fourth to sixth grade (21,893 pupils) and all junior high pupils from the first to third year (21,737 pupils) in Niigata City (population of 785,067). 26,766 pupils who were determined to have valid responses (valid response rate 61.3%) were analyzed. Among the 26,766 pupils with valid responses, 2,591 (9.7%) had LBP at the time of the survey, and 8,588 (32.1%) had a history of LBP. The pupils were divided between those who did not participate in sports activities except the physical education in school (No sports group: 5,486, 20.5%) and those who participated in sports activities (Sports group: 21,280, 79.5%), and the difference in lifetime prevalence between No sports group and Sports group was examined. The odds ratio for LBP according to sports activity was calculated by multiple logistic regression analysis adjusted for gender, age, and body mass index. In addition, the severity of LBP was divided into three levels (Level 1: no limitation in any activity, Level 2: necessary to refrain from participating in sports and physical activities, and Level 3: necessary to be absent from school), and Levels 2 and 3 were defined as severe LBP; the severity was compared between No sports group and Sports group and in each sport's items. Moreover, in Sports group, the amount of time spent participating in sports activities were divided into three groups (Group 1: less than 6 h per week, Group 2: 6-12 h per week, and Group 3: 12.1 h per week or more), and the dose-response between the amount of time spent participating in sports activities and the occurrence of LBP were compared. In No sports group, 21.3% experienced a history of LBP; in Sports group, 34.9% experienced LBP (P < 0.001). In comparison to No sports group, the odds ratio was significantly higher for Sports group (1.57), and also significantly higher for most of the sports items. The severity of LBP was significantly higher in Sports group (20.1 vs. 3.2%, P < 0.001). The amount of time spent participating in sports activities averaged 9.8 h per week, and a history of LBP significantly increased in the group which spent a longer time participating in sports activities (odds ratio 1.43 in Group 3). These findings suggest that sports activity is possible risk factors for the occurrence of LBP, and it might increase the risk for LBP in childhood and adolescence. PMID- 20582558 TI - Post-traumatic thoracic scoliosis with rib head dislocation and intrusion into the spinal canal: a case report and review of literature. AB - The objective of the study was to report a rare occurrence of dislocation and intrusion of two rib heads into the spinal canal at the convex apex of a post traumatic thoracic scoliosis in an adult in the absence of any neurological impairment. A 47-year-old male presented with a slowly progressive, post traumatic thoracic scoliosis and a mild aching sensation over the posterior chest wall. The lower limb neurology and bowel and bladder function were normal. There was no clinical evidence of neurofibromatosis. CT scans showed that the 8th and 9th ribs on the convex apex of the scoliotic curve had intruded into the spinal canal and were lying adjacent to the dura and spinal cord. The MRI scan did not show any cord signal intensity changes. Although rib dislocation and intrusion into the spinal canal is uncommon, images should be carefully analysed to rule out this condition in sharp angular scoliotic curves. PMID- 20582560 TI - The perceptual origins of the abstract same/different concept in human infants. AB - Very few experiments have studied the two item same/different relation in young human infants. This contrasts with an extensive animal literature. We tested young infants with two novel tasks designed specifically to provide convergent comparative measures. Each infant completed both tasks allowing an assessment of their understanding of the abstract concept rather than task-specific abilities. In a looking time task with photographic stimuli, we found that 8-month-olds are sensitive to the relation but 4-month-olds are not. The second task used an anticipatory eye movement paradigm with simple geometric stimuli. On each trial, two colored shapes appear and moved upwards behind an occluder. They reappeared on either the upper left or right depending on the relation between them. Infants at both ages learned and generalized the dependency but only for the different relation. These results show that human infants can learn the same/different concept but that, in strong continuity with animal results, their abilities are firmly grounded in perception. PMID- 20582559 TI - Inhibition and stimulation of formation of the ferroxidase center and the iron core in Pyrococcus furiosus ferritin. AB - Ferritin is a ubiquitous iron-storage protein that has 24 subunits. Each subunit of ferritins that exhibit high Fe(II) oxidation rates has a diiron binding site, the so-called ferroxidase center (FC). The role of the FC appears to be essential for the iron-oxidation catalysis of ferritins. Studies of the iron oxidation by mammalian, bacterial, and archaeal ferritin have indicated different mechanisms are operative for Fe(II) oxidation, and for inhibition of the Fe(II) oxidation by Zn(II). These differences are presumably related to the variations in the amino acid residues of the FC and/or transport channels. We have used a combination of UV-vis spectroscopy, fluorescence spectroscopy, and isothermal titration calorimetry to study the inhibiting action of Zn(II) ions on the iron-oxidation process by apoferritin and by ferritin aerobically preloaded with 48 Fe(II) per 24-meric protein, and to study a possible role of phosphate in initial iron mineralization by Pyrococcus furiosus ferritin (PfFtn). Although the empty FC can accommodate two zinc ions, binding of one zinc ion to the FC suffices to essentially abolish iron-oxidation activity. Zn(II) no longer binds to the FC nor does it inhibit iron core formation once the FC is filled with two Fe(III). Phosphate and vanadate facilitate iron oxidation only after formation of a stable FC, whereupon they become an integral part of the core. These results corroborate our previous proposal that the FC in PfFtn is a stable prosthetic group, and they suggest that its formation is essential for iron-oxidation catalysis by the protein. PMID- 20582561 TI - Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine. AB - A 36-year-old female patient who was diagnosed with chronic myocarditis as an initial manifestation of systemic lupus erythematosus (SLE) was admitted to our hospital. At her third occurrence of heart failure, we performed an endomyocardial biopsy and proved chronic myocarditis with SLE. Subsequently, she was treated with prednisolone and the immunosuppressive agent mizoribine (MZR), and her cardiac function improved. We describe for the first time treatment with MZR for chronic cardiac involvement of SLE. PMID- 20582562 TI - Monitoring of perceptions, anticipated behavioral, and psychological responses related to H5N1 influenza. AB - BACKGROUND: The aim of this study was to monitor changes in behavioral and emotional responses to human H5N1 in the community over a 28-month period (from November 2005 to February 2008). METHODS: A total of 3,527 Hong Kong Chinese adults were interviewed by telephone within the framework of six identical cross sectional surveys carried out during the 28-month study period. Given a hypothetical scenario that two to three new human-to-human H5N1 cases had been reported in Hong Kong, the trends of the respondents in various H5N1-related risk perceptions, anticipated personal psychological responses, and anticipated personal preventive behaviors were investigated. RESULTS: Over time, a decreased proportion of the respondents (1) felt susceptible to contracting H5N1, (2) expected a large outbreak would eventually occur, (3) believed that the impacts of H5N1 were worse than those of severe acute respiratory syndrome (SARS), and (4) anticipated adopting more types of preventive measures and experiencing mental distress in the case of a small-scale outbreak in Hong Kong (AOR from 0.27 to 0.43, p < 0.001), but the public remained vigilant on public health behaviors, such as hand-washing. The prevalence of misconceptions on the mode of transmission declined, but remained high; perceptions on the fatality of H5N1 remained largely underestimated. The SARS experience and unconfirmed beliefs about the transmission modes were associated with variables on anticipated preventive behaviors and emotional distress. CONCLUSION: Starting in 2005 through to 2008, respondents perceived a decreasing level of susceptibility, severity, and anticipated stress towards a hypothetical human-to-human H5N1 outbreak, possibly due to the low efficiency of transmission. The public's general preparedness was still relatively good and rational, even though individual preventive behaviors were less common. However, misconceptions were prevalent among the respondents. Based on these results, public education is warranted to rectify these misconceptions. PMID- 20582563 TI - The effect of formalin fixation on the levels of brain transition metals in archived samples. AB - Reports that iron, zinc and copper homeostasis are in aberrant homeostasis are common for various neurodegenerative diseases, particularly for Huntington's disease, Parkinson's disease, and Alzheimer's disease. Manipulating the levels of these elements in the brain through the application of chelators has been and continues to be tested therapeutically in clinical trials with mixed results. Much of the data indicating that these metals are abnormally concentrated in Alzheimer's disease and Parkinson's disease brain tissue was generated through the analysis of post-mortem human tissue which was archived in formalin. In this study, we evaluated the effect of formalin fixation of brain on the levels of three important transition metals (iron, copper, and zinc) by atomic absorption spectroscopy. Paired brain specimens were obtained at autopsy for each case; one was conserved by formalin archival (averaging four years), the other was rapidly frozen. Both white and grey matter samples were analyzed and the concentrations of iron and zinc were found to decrease with fixation. Iron was reduced by 40% (P < 0.01), and zinc by 77% (P < 0.0001); copper concentrations increased by 37% (P < 0.05) by the paired T-test. The increase in copper is likely due to contamination from trace copper in the formalin. These results indicate that transition metal data obtained from fixed tissue may be heavily distorted and care should be taken in interpreting this data. PMID- 20582564 TI - When biased language use is associated with bullying and dominance behavior: the moderating effect of prejudice. AB - Biased language related to sexual orientation is used frequently among students and is related to prominent social concerns such as bullying. Prejudice toward gay, lesbian, bisexual, and transgender individuals also has been examined among adolescents, but separately from these behaviors. This study tested whether biased language use was associated with bullying and dominance irrespective of sexual prejudice or if sexual prejudice moderated these associations among 290 high school students (50% female; 56% White). Sexual prejudice was associated with biased language use among boys only. Biased language was associated with bullying regardless of levels of sexual prejudice for boys. However, this association was dependent on sexual prejudice for girls. For dominance behavior, its association with biased language was moderated by sexual prejudice for boys, but not girls. However, girls' engagement in all behaviors was significantly less than boys. These results indicate nuanced ways in which multiple factors contribute to the use of sexual orientation biased language. Also, they underscore the need to address biased language and prejudice as part of anti bullying programs. PMID- 20582565 TI - Developmental experiences during extracurricular activities and Australian adolescents' self-concept: particularly important for youth from disadvantaged schools. AB - Extracurricular activities provide adolescents with a number of positive personal and interpersonal developmental experiences. This study investigated whether developmental experiences that occurred during extracurricular activities were linked to a more positive self-concept for Australian adolescents, and whether this link was particularly salient for youth from disadvantaged schools. Adolescents (N = 1,504, 56% Female) from 26 diverse high schools across Western Australia were surveyed. The findings revealed that adolescents from low socio economic status schools who participated in extracurricular activities had a more positive general self-worth and social self-concept than adolescents from similar socio-economic schools who did not participate in any extracurricular activities. Furthermore, the positive developmental experiences that occurred during extracurricular activities predicted a more positive general self-worth and social and academic self-concept, and this link was stronger for youth from low SES schools. These findings suggest that the developmental experiences afforded by extracurricular activities may foster positive adolescent development. PMID- 20582566 TI - Estimating the directed information to infer causal relationships in ensemble neural spike train recordings. AB - Advances in recording technologies have given neuroscience researchers access to large amounts of data, in particular, simultaneous, individual recordings of large groups of neurons in different parts of the brain. A variety of quantitative techniques have been utilized to analyze the spiking activities of the neurons to elucidate the functional connectivity of the recorded neurons. In the past, researchers have used correlative measures. More recently, to better capture the dynamic, complex relationships present in the data, neuroscientists have employed causal measures-most of which are variants of Granger causality with limited success. This paper motivates the directed information, an information and control theoretic concept, as a modality-independent embodiment of Granger's original notion of causality. Key properties include: (a) it is nonzero if and only if one process causally influences another, and (b) its specific value can be interpreted as the strength of a causal relationship. We next describe how the causally conditioned directed information between two processes given knowledge of others provides a network version of causality: it is nonzero if and only if, in the presence of the present and past of other processes, one process causally influences another. This notion is shown to be able to differentiate between true direct causal influences, common inputs, and cascade effects in more two processes. We next describe a procedure to estimate the directed information on neural spike trains using point process generalized linear models, maximum likelihood estimation and information-theoretic model order selection. We demonstrate that on a simulated network of neurons, it (a) correctly identifies all pairwise causal relationships and (b) correctly identifies network causal relationships. This procedure is then used to analyze ensemble spike train recordings in primary motor cortex of an awake monkey while performing target reaching tasks, uncovering causal relationships whose directionality are consistent with predictions made from the wave propagation of simultaneously recorded local field potentials. PMID- 20582567 TI - Mitochondrial and chromosomal insights into karyotypic evolution of the pygmy mouse, Mus minutoides, in South Africa. AB - The African pygmy mouse, Mus minutoides, displays extensive Robertsonian (Rb) diversity. The two extremes of the karyotypic range are found in South Africa, with populations carrying 2n = 34 and 2n = 18. In order to reconstruct the scenario of chromosomal evolution of M. minutoides and test the performance of Rb fusions in resolving fine-scale phylogenetic relationships, we first describe new karyotypes, and then perform phylogenetic analyses by two independent methods, using respectively mitochondrial cytochrome b sequences and chromosomal rearrangements as markers. The molecular and chromosomal phylogenies were in perfect congruence, providing strong confidence both for the tree topology and the chronology of chromosomal rearrangements. The analysis supports a division of South African specimens into two clades showing opposite trends of chromosomal evolution, one containing all specimens with 34 chromosomes (karyotypic stasis) and the other grouping all mice with 18 chromosomes that have further diversified by the fixation of different Rb fusions (extensive karyotypic reshuffling). The results confirm that Rb fusions are by far the predominant rearrangement in M. minutoides but strongly suggest that recurrent whole-arm reciprocal translocations have also shaped this genome. PMID- 20582568 TI - Intranigral LPS administration produces dopamine, glutathione but not behavioral impairment in comparison to MPTP and 6-OHDA neurotoxin models of Parkinson's disease. AB - The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre motor phase of Parkinson's disease. PMID- 20582569 TI - Hairpin transcription does not necessarily lead to efficient triggering of the RNAi pathway. AB - Previously, we had shown that stable expression of a hairpin RNA sharing homology with the coat protein (CP) of the Cucumber mosaic virus (CMV) (hpRNA(CMV)) produced CMV resistant Nicotiana tabacum plants. However, only 17% of the hpRNA(CMV)-expressing plants generated substantial amounts of siRNAs that mediated CMV resistance (siRNAs(CMV)). Here, we demonstrate that the transcription of a hpRNA(CMV) per se is not sufficient to trigger cytoplasmic and nuclear RNAi. A multiple-transgene copy line showed a strong resistance phenotype. Segregation of individual copies revealed that in one locus, the transgene-produced hpRNA(CMV) transcript was processed into 21-nt and 24-nt siRNAs(CMV) and lines containing this locus were resistant. At a second locus, where the transgene was shown to be transcribed, no siRNAs(CMV) were produced and lines harbouring only this locus were susceptible. In addition, the second locus failed to trigger de novo RNA-directed DNA methylation (RdDM) in cis, of its cognate sequence. However, after being induced in trans, methylation in the transcribed region of the transgene was maintained in both CG and CHG residues. Sequence-specific maintenance of methylation in transcribed regions, as well as diverse RNA degradation pathways in plants are discussed in view of our observations. PMID- 20582570 TI - Evaluation of Client Services (ECS): a measure of treatment satisfaction for people with chronic mental illnesses. AB - This article describes the development and psychometric assessment of the Evaluation of Client Services (ECS) measure of treatment satisfaction for people with chronic mental illnesses in community treatment settings. The ECS, a 20-item instrument, was validated in a sample of 184 individuals receiving outpatient mental health treatment in New York City. The four dimensions of the ECS, (1) treatment management and treatment outcome, (2) treatment relationship, (3) communication and information exchange, and (4) reachability of treatment facilities are internally consistent and stable over time. Analyses also show that the ECS is a valid indicator of satisfaction with mental health services which meaningfully correlates with quality of life and another measure of treatment satisfaction. The ECS is a brief and easy to understand treatment satisfaction tool with good psychometric properties. PMID- 20582571 TI - "That Could Be Me Squishing Chips on Someone's Car." How Friends Can Positively Influence Bullying Behaviors. AB - Semi-structured one-on-one interviews with a purposive sample of 51 grade 7 students (12 years old) who reported bullying others explored what might encourage students to stop bullying others. The theoretical perspectives of symbolic interactionism, in particular the development of self and definition of the situation, were used to inform this study. Dissonance theory was used to understand how students felt about their bullying behaviors. The theme of peer group emerged as an influence when considering desisting bullying others. Feelings of dissonance reinforced by peers and the need to be accepted by peers facilitated positive changes if significant peers disapproved of bullying. Some students changed friendship groups to move away from negative situations, representing significant development of self. School-based programs can work to enhance the positive influence of prosocial students, to focus on the development of self, and to reduce the social status achieved by some through bullying others. PMID- 20582572 TI - Colored potato extracts induce superoxide dismutase-2 mRNA via ERK1/2 pathway in HepG2 cells. AB - Rats fed a diet containing Shadow Queen (SQ), an anthocyanin-rich potato cultivar, previously showed an increase in the hepatic superoxide dismutase (SOD) 2 mRNA level. We investigated whether an extract of SQ would directly increase the hepatic SOD-2 mRNA level in HepG2 cells. Furthermore, we estimated the intracellular signaling pathway for the induction of SOD-2 mRNA expression. HepG2 cells were stimulated using extracts of four crops, including SQ, for 12 h; only extracts of colored potatoes induced SOD-2 mRNA expression significantly. This induction of SOD-2 mRNA expression was blocked by an inhibitor of the extracellular signal-related kinase (ERK) 1/2 pathway. Furthermore, an extract of SQ increased the phosphorylation of ERK1/2 after 15 or 30 min of stimulation. These data indicate that an extract of SQ directly induces hepatic SOD-2 mRNA expression via activation of ERK1/2 pathway in HepG2 cells. PMID- 20582573 TI - Comparing respondent-driven sampling and targeted sampling methods of recruiting injection drug users in San Francisco. AB - The objective of this article is to compare demographic characteristics, risk behaviors, and service utilization among injection drug users (IDUs) recruited from two separate studies in San Francisco in 2005, one which used targeted sampling (TS) and the other which used respondent-driven sampling (RDS). IDUs were recruited using TS (n = 651) and RDS (n = 534) and participated in quantitative interviews that included demographic characteristics, risk behaviors, and service utilization. Prevalence estimates and 95% confidence intervals (CIs) were calculated to assess whether there were differences in these variables by sampling method. There was overlap in 95% CIs for all demographic variables except African American race (TS: 45%, 53%; RDS: 29%, 44%). Maps showed that the proportion of IDUs distributed across zip codes were similar for the TS and RDS sample, with the exception of a single zip code that was more represented in the TS sample. This zip code includes an isolated, predominantly African American neighborhood where only the TS study had a field site. Risk behavior estimates were similar for both TS and RDS samples, although self-reported hepatitis C infection was lower in the RDS sample. In terms of service utilization, more IDUs in the RDS sample reported no recent use of drug treatment and syringe exchange program services. Our study suggests that perhaps a hybrid sampling plan is best suited for recruiting IDUs in San Francisco, whereby the more intensive ethnographic and secondary analysis components of TS would aid in the planning of seed placement and field locations for RDS. PMID- 20582574 TI - Understanding the significance, reasons and patterns of abnormal vital signs after gastric bypass for morbid obesity. AB - Anastomotic leaks and bleeding are the two most feared major complications in patients undergoing laparoscopic gastric bypass (LRYGB). This study was designed to evaluate if there is a clinical correlation between abnormal vital signs and postoperative leaks and bleeding. After IRB approval and adherence to HIPAA guidelines, a retrospective review of medical records was performed on 518 patients who underwent LRYGB between October 2002 and October 2006. Vital signs from each patient were monitored hourly. Eight patients out of 518 (1.54%) were discovered to have anastomotic leak. A marked increase in heart rate up to 120 bpm at 20 h after surgery occurred in five of eight patients (62.5%). Of the eight patients who had a leak, seven (87.5%) experienced sustained tachycardia above 120 bpm. On the other hand, 20 patients out of 518 (3.86%) were discovered to have postoperative bleeding. A gradual rather than a dramatic increase in heart rate was recorded in 17 of 20 patients (85%) starting 8 h after surgery. Five patients (25%) had unsustained tachycardia above 120 bpm. Twelve patients in this group (60%) were seen to have cyclical tachycardia that never exceeded 120 bpm at any point during hospitalization. Marginal hypotension was found in seven patients (35%) in this group. Sustained tachycardia with a heart rate exceeding 120 bpm appears to be an indicator of anastomotic leak. Tachycardia less than 120 bpm that has occurred in a cyclical pattern strongly pointed toward postoperative bleeding. Anastomotic leaks and bleeding are the two most feared major complications in patients undergoing LRYGB. This study was designed to evaluate if there is a clinical correlation between abnormal vital signs and postoperative leaks and bleeding. PMID- 20582575 TI - Symposium on nutritional anemia. Editorial. PMID- 20582576 TI - Modified escalated BEACOPP as salvage chemotherapy in classic Hodgkin lymphoma. PMID- 20582577 TI - Effect of wild type PTEN gene on proliferation and invasion of multiple myeloma. AB - We explored the effect of the wild type PTEN gene on the proliferation, apoptosis and invasive ability of multiple myeloma (MM) cells from MM patients and RPMI 8226 cells (a human myeloma cell line), and the effect of the PTEN/focal adhesion kinase (FAK)/MMP signaling pathway on the invasion activity of RPMI 8226 cells. The proliferation of RPMI 8226 cells and purified myeloma cells from MM patients were markedly inhibited after these cells were transfected with recombinant adenovirus-PTEN vectors containing green fluorescent protein (Ad-PTEN-GFP). Maximum growth inhibition of RPMI 8226 cells and purified myeloma cells from MM patients by AD-PTEN-GFP was 42.01 and 24.75%, respectively. After transfection with PTEN-siRNA, the proliferation of RPMI 8226 cells was increased significantly compared with NS-siRNA transfected controls. The maximal survival rate was 141.55 +/- 8.34% in PTEN-siRNA transfected RPMI 8226 cells. Apoptosis of RPMI 8226 cells or purified myeloma cells from MM patients in the Ad-PTEN-GFP group was increased significantly when compared with that in the Ad-GFP (adenovirus vectors only expressing green fluorescent protein) group (p < 0.01). The cell cycle of RPMI 8226 cells was arrested at the G2/M phase. Furthermore, the number of cells that migrated through the matrigel and filter from the upper chamber to the lower chamber in the transwell assay in the Ad-GFP group was significantly larger than that in the Ad-PTEN-GFP group (52.65 +/- 7.39 vs. 23.50 +/- 6.12, p < 0.01). In the PTEN-siRNA group, the cell number (79.50 +/- 11.89) was significantly larger than that in the NS-siRNA group (47.17 +/- 7.76, p < 0.01). When RPMI 8226 cells were transfected with Ad-PTEN-GFP or NS-siRNA, the expression level of PTEN mRNA was up-regulated, and the expression levels of FAK, MMP-2 and MMP-9 mRNA were down-regulated significantly compared with that of the Ad-GFP group and the PTEN siRNA group (p < 0.01, p < 0.05). The protein levels of FAK and p-FAK, MMP-2 and MMP-9 in RPMI 8226 cells which were transfected with Ad-PTEN-GFP decreased significantly, but increased significantly in PTEN-siRNA transfected RPMI 8226 cells (p < 0.01, p<0.05). These results indicated that wild type PTEN, which inhibited FAK, MMP-2, and MMP-9, could suppress the proliferation and invasion ability of multiple myeloma cells. Modulating the expression of PTEN may be a potential strategy for the treatment of multiple myeloma. PMID- 20582578 TI - Development of a population pharmacokinetic model for taranabant, a cannibinoid-1 receptor inverse agonist. AB - Taranabant is a cannabinoid-1 receptor inverse agonist developed for the treatment of obesity. A population model was constructed to facilitate the estimation of pharmacokinetic parameters and to identify the influence of selected covariates. Data from 12 phase 1 studies and one phase 2 study were pooled from subjects administered single and multiple oral doses of taranabant ranging from 0.5 to 8 mg. A total of 6,834 taranabant plasma concentrations from 187 healthy and 385 obese subjects were used to develop the population model in NONMEM. A standard covariate analysis using forward selection (alpha = 0.05) and backward elimination (alpha = 0.001) was conducted. A three-compartment model with first-order absorption and elimination adequately described plasma taranabant concentrations. The population mean estimates for apparent clearance and apparent steady-state volume of distribution were 25.4 L/h and 2,578 L, respectively. Statistically significant covariate effects were modest in magnitude and not considered clinically relevant (the effects of body mass index (BMI) and creatinine clearance (CrCL) on apparent clearance; BMI, age, CrCL, and gender on apparent volume of the peripheral compartment and age on apparent intercompartmental clearance). The pharmacokinetic profile of taranabant can adequately be described by a three-compartment model with first-order absorption and elimination. Clinical dose adjustment based on covariates effects is not warranted. PMID- 20582579 TI - Breast cancer resistance protein (BCRP) and sulfotransferases contribute significantly to the disposition of genistein in mouse intestine. AB - The low bioavailability of genistein has impeded its development into a therapeutic agent. Our earlier studies indicate that glucuronidation is one of the major barriers to genistein oral bioavailability. This study will determine how sulfotransferases and efflux transporters affect its intestinal disposition. A rodent intestinal perfusion model and S9 fractions were used. Sulfate excretion rates were comparable to glucuronide excretion in mouse small intestine but significantly higher than glucuronide excretion in mouse colon, which is different from rat intestinal disposition but similar to disposition in Caco-2 cells. To define efflux transporter(s) involved in sulfate excretion, two organic anion inhibitors (estrone sulfate and dihydroepiandrosterone sulfate) or a multidrug resistance protein inhibitor (MK-571) were used but neither was able to decrease the excretion of genistein sulfates. In contrast, the excretion of genistein sulfate decreased substantially (>90%) in small intestine of breast cancer resistance protein (BCRP) knockout mice and became undetectable in colon of the knockout mice. The excretion rates of genistein glucuronide in the small intestine of BCRP knockout mice were also significant decreased (78%). This study shows clearly that BCRP facilitates the cellular genistein sulfate excretion by removing sulfates to prevent their backward hydrolysis and to limit substrate inhibition, indicating that BCRP plays a dominant role in genistein sulfate excretion and a significant role in genistein glucuronide excretion in the mouse intestine. PMID- 20582580 TI - PKC delta mediates pro-inflammatory responses in a mouse model of caerulein induced acute pancreatitis. AB - Acute pancreatitis is an inflammatory disorder of the pancreas. Protein kinase C (PKC) delta plays an important role in mediating chemokine production in mouse pancreatic acinar cells. This study aims to investigate the role of PKC delta in the pathogenesis of acute pancreatitis and to explore the mechanisms through which PKC delta mediates pro-inflammatory signaling. Acute pancreatitis was induced in mice by ten hourly intraperitoneal injections of caerulein. PKC delta translocation inhibitor peptide (deltaV1-1) at a dose of 1.0 mg/kg or Tat (carrier peptide) at a dose of 1.0 mg/kg was administered to mice either 1 h before or 1 h after the first caerulein injection. One hour after the last caerulein injection, the mice were killed and pancreas, lungs, and blood were collected. Prophylactic and therapeutic treatment with deltaV1-1 attenuated caerulein-induced plasma amylase levels and pancreatic edema. Treatment with deltaV1-1 decreased myeloperoxidase activity and monocyte chemotactic protein-1 levels in both pancreas and plasma. PKC delta mediated acute pancreatitis by activating pancreatic nuclear factor kappaB, activator protein-1, and mitogen activated protein kinases. Moreover, blockade of PKC delta attenuated lung myeloperoxidase activity and edema. Histological examination of pancreatic and lung sections confirmed protection against acute pancreatitis. Treatment with Tat had no protective effect on acute pancreatitis. Blockade of PKC delta represents a promising prophylactic and/or therapeutic tool for the treatment of acute pancreatitis. PMID- 20582581 TI - Transcription factor profiling leading to the identification of putative transcription factors involved in the Medicago truncatula-Uromyces striatus interaction. AB - Understanding the host response to Uromyces sp., the causal agent of rust in many crop species, is crucial in elucidating the specific biology of rust resistance. In an attempt to unravel the Medicago truncatula-U. striatus interaction, we performed a global analysis of transcription factor (TF) expression in resistant and susceptible accessions of the model plant M. truncatula during infection with U. striatus. For this purpose, an established qPCR platform was applied, consisting of specific primer pairs for more than 1,000 predicted TF genes. A total of 107 putative TF genes out of the 1,084 studied were differentially expressed. Thirteen of the TFs that were differentially expressed between resistant and susceptible genotypes are known to be relevant in cellular defense. These data suggest that resistance could be mediated both by genes that are constitutively expressed and by genes, which are activated/repressed when plants are inoculated. These defense related TFs sequences were amplified in chickpea DNA with the aim of determining the location of these genes on the genetic map of this crop and identifying possible DNA regions involved in resistance mechanisms. PMID- 20582582 TI - Concentration and gas-particle partitioning of hexachlorobenzene in the ambient air before and after the Beijing Olympic Games. AB - Systematic studies of hexachlorobenzene in the ambient air before and after the Beijing Olympic Games were carried out during July 2007 to March 2009. Air samples were collected around 20th monthly on the roof of a building near the Olympic center. The average concentration of hexachlorobenzene was 264 pg x m( 3), which was higher in winter than other seasons. However, hexachlorobenzene concentration was decreased clearly in winter in 2008 compare with in 2007 due to the implementation of a series of "Green Olympic" policies. Gas-particle partitioning shows that the increase of hexachlorobenzene levels in winter time was mainly contributed by the high total suspended particulate from combustion processes such as coal-burning and traffic emission. PMID- 20582583 TI - Extracellular matrix produced by osteoblasts cultured under low-magnitude, high frequency stimulation is favourable to osteogenic differentiation of mesenchymal stem cells. AB - The effects of low-magnitude, high-frequency (LMHF) mechanical stimulation on osteoblastic cells are poorly understood. We have developed a system that generates very small (15-40 MUepsilon), high-frequency (400 Hz, sine) deformations on osteoblast cultures (MC3T3-E1). We investigated the effects of these LMHF stimulations mainly on extracellular matrix (ECM) synthesis. The functional properties of this ECM after decellularization were evaluated on C3H10T1/2 mesenchymal stem cells (MSCs). LMHF stimulations were applied 20 min once daily for 1, 3, or 7 days in MC3T3-E1 culture (1, 3, or 7 dLMHF). Cell number and viability were not affected after 3 or 7 dLMHF. Osteoblast response to LMHF was assessed by an increase in nitric oxide secretion, alteration of the cytoskeleton, and focal contacts. mRNA expression for fibronectin, osteopontin, bone sialoprotein, and type I collagen in LMHF cultures were 1.8-, 1.6-, 1.5-, and 1.7-fold higher than controls, respectively (P < 0.05). In terms of protein, osteopontin levels were increased after 3 dLMHF and ECM organization was altered as shown by fibronectin topology after 7 dLMHF. After decellularization, 7 dLMHF ECM or control ECM was reseeded with MSCs. Seven dLMHF-ECM improved early events such as cell attachment (2 h) and focal contact adhesion (6 h) and, later (16 h), modified MSC morphological parameters. After 5 days in multipotential medium, gene-expression changes indicated that 7 dLMHF-ECM promoted the expression of osteoblast markers at the expense of adipogenic marker. LMHF stimulations of osteoblasts are therefore efficient and sufficient to generate osteogenic matrix. PMID- 20582585 TI - Acquired factor VIII haemophilia following influenza vaccination. PMID- 20582586 TI - Assessment of MTBE biodegradation pathways by two-dimensional isotope analysis in mixed bacterial consortia under different redox conditions. AB - The fuel oxygenate, methyl tert-butyl ether (MTBE), although now widely banned or substituted, remains a persistent groundwater contaminant. Multidimensional compound-specific isotope analysis (CSIA) of carbon and hydrogen is being developed for determining the extent of MTBE loss due to biodegradation and can also potentially distinguish between different biodegradation pathways. Carbon and hydrogen isotopic fractionation factors were determined for MTBE degradation in aerobic and anaerobic laboratory cultures. The carbon isotopic enrichment factor (epsilonC) for aerobic MTBE degradation by a bacterial consortium containing the aerobic MTBE-degrading bacterium, Variovorax paradoxus, was -1.1 +/- 0.2 per thousand and the hydrogen isotope enrichment factor (epsilonH) was 15 +/- 2 per thousand. This corresponds to an approximated lambda value (Lambda = epsilonH/epsilonC) of 14. Carbon isotope enrichment factors for anaerobic MTBE degrading enrichment cultures were -7.0 +/- 0.2 per thousand and did not vary based on the original inoculum source, redox condition of the enrichment, or supplementation with syringic acid as a co-substrate. The hydrogen enrichment factors of cultures without syringic acid were insignificant, however a strong hydrogen enrichment factor of -41 +/- 3 per thousand was observed for cultures which were fed syringic acid during MTBE degradation. The Lambda = 6 obtained for NYsyr cultures might be diagnostic for the stimulation of anaerobic MTBE degradation by methoxylated compounds by an as yet unknown pathway and mechanism. The stable-isotope enrichment factors determined in this study will enhance the use of CSIA for monitoring anaerobic and aerobic MTBE biodegradation in situ. PMID- 20582587 TI - Selection and characterization of DNA aptamers with binding selectivity to Campylobacter jejuni using whole-cell SELEX. AB - The need for pre-analytical sample processing prior to the application of rapid molecular-based detection of pathogens in food and environmental samples is well established. Although immunocapture has been applied in this regard, alternative ligands such as nucleic acid aptamers have advantages over antibodies such as low cost, ease of production and modification, and comparable stability. To identify DNA aptamers demonstrating binding specificity to Campylobacter jejuni cells, a whole-cell Systemic Evolution of Ligands by EXponential enrichment (SELEX) method was applied to a combinatorial library of FAM-labeled single-stranded DNA molecules. FAM-labeled aptamer sequences with high binding affinity to C. jejuni A9a as determined by flow cytometric analysis were identified. Aptamer ONS-23, which showed particularly high binding affinity in preliminary studies, was chosen for further characterization. This aptamer displayed a dissociation constant (K(d) value) of 292.8 +/- 53.1 nM with 47.27 +/- 5.58% cells fluorescent (bound) in a 1.48-microM aptamer solution. Binding assays to assess the specificity of aptamer ONS-23 showed high binding affinity (25-36%) for all other C. jejuni strains screened (inclusivity) and low apparent binding affinity (1-5%) with non-C. jejuni strains (exclusivity). Whole-cell SELEX is a promising technique to design aptamer-based molecular probes for microbial pathogens without tedious isolation and purification of complex markers or targets. PMID- 20582584 TI - Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy. AB - Genetic factors contribute to the phenotype of drug response, but the translation of pharmacogenetic outcomes into drug discovery, drug development or clinical practice has proved to be surprisingly disappointing. Despite significant progress in pharmacogenetic research, only a few drugs, such as cetuximab, dasatinib, maraviroc and trastuzumab, require a pharmacogenetic test before being prescribed. There are several gaps that limit the application of pharmacogenetics based upon the complex nature of the drug response itself. First, pharmacogenetic tests could be more clinically applicable if they included a comprehensive survey of variation in the human genome and took into account the multigenic nature of many phenotypes of drug disposition and response. Unfortunately, much of the existing research in this area has been hampered by limitations in study designs and the nonoptimal selection of gene variants. Secondly, although responses to drugs can be influenced by the environment, only fragmentary information is currently available on how the interplay between genetics and environment affects drug response. Third, the use of a pharmacogenetic test as a standard of care for drug therapy has to overcome significant scientific, economic, commercial, political and educational barriers, among others, in order for clinically useful information to be effectively communicated to practitioners and patients. Meanwhile, the lack of efficacy is in this process is quite as costly as drug toxicity, especially for very expensive drugs, and there is a widespread need for clinically and commercially robust pharmacogenetic testing to be applied. In this complex scenario, therapeutic drug monitoring of parent drugs and/or metabolites, alone or combined with available pharmacogenetic tests, may be an alternative or complementary approach when attempts are made to individualize dosing regimen, maximize drug efficacy and enhance drug safety with certain drugs and populations (e.g. antidepressants in older people). PMID- 20582588 TI - Extending the alkene substrate range of vinyl chloride utilizing Nocardioides sp. strain JS614 with ethene oxide. AB - Nocardioides sp. strain JS614 grows on the C(2) alkenes ethene (Eth), vinyl chloride, and vinyl fluoride as sole carbon sources. The presence of 400-800 microM ethene oxide (EtO) extended the growth substrate range to propene (C(3)) and butene (C(4)). Propene-dependent growth of JS614 was CO(2) dependent and was prevented by the carboxylase/reductase inhibitor 2-bromoethanesulfonic acid, sodium salt (BES), while growth on Eth was not CO(2) dependent or BES sensitive. Although unable to promote growth, both propene and propene oxide (PrO)-induced expression of the genes encoding the alpha subunit of alkene monooxygenase (etnC) and epoxyethane CoM transferase (etnE) to similar levels as did Eth and EtO. Propene was transformed by Eth-grown and propene-grown/EtO-induced JS614 to PrO at a rate 4.2 times faster than PrO was consumed. As a result PrO accumulated in growth medium to 900 microM during EtO-induced growth on propene. PrO (50-100 microM) exerted inhibitory effects on growth of JS614 on both acetate and Eth, and on EtO-induced growth on Eth. However, higher EtO concentrations (300-400 microM) overcame the negative effects of PrO on Eth-dependent growth. PMID- 20582589 TI - The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer. AB - BACKGROUND: Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer. METHODS: The number, IFN gamma production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro. RESULTS: The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-gamma production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity. CONCLUSION: NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy. PMID- 20582591 TI - Socializing makes thick-skinned individuals: on the density of epidermal alarm substance cells in cyprinid fish, the crucian carp (Carassius carassius). AB - In cyprinid fish, density of epidermal club cells (i.e. alarm substance cells) has been found to vary between lakes with different predator fauna. Because predators can be labelled with chemical cues from prey, we questioned if club cell density could be controlled indirectly by predators releasing prey cues. In particular, we suspected a possible feedback mechanism between chemical alarm signals and their cellular source. We raised crucian carp singly and in groups of four. For both rearing types, fish were exposed to skin extracts of either conspecifics or brown trout (without club cells), and provided either low or high food rations. Independent of rearing type, condition factor and club cell density increased with food ration size, but no change was found in club cell density following exposure to conspecific alarm signals. However, the density of club cells was found significantly higher for fish raised in groups than for fish raised alone. We conclude that an increased condition factor results in more club cells, but crucian carp may also possess an awareness of conspecific presence, given by higher club cell densities when raised in groups. This increase in club cell density may be induced by unknown chemical factors released by conspecifics. PMID- 20582592 TI - Neurocutaneous vascular syndromes. AB - There have been significant recent advances in the past several years in the field of neurocutaneous vascular syndromes, including the development of more stringent diagnostic criteria for PHACE syndrome, the renaming of macrocephaly cutis marmorata telangiectatica congenita to macrocephaly-capillary malformation to accurately reflect the true nature of the syndrome, and discovery of new genetic mutations such as RASA-1. There have also been advances in the understanding and management of Sturge-Weber syndrome.PHACE syndrome is a constellation of neurologic, arterial, cardiac, ophthalmologic, and sternal abnormalities associated with infantile hemangiomas. PHACE is an acronym for Posterior fossa malformation, Hemangioma, Arterial anomalies, Coarctation of the aorta, Eye abnormalities. Some authors include an "S" for PHACE(S) to denote the association of ventral defects including Sternal clefting and Supraumbilical raphe.The accurate diagnosis and work-up of these patients require coordination of care across multiple disciplines, including neuroradiology, radiology, dermatology, neurology, surgery, and interventional radiology, among others.This paper is meant to update clinicians and researchers about important advances in these rare, important vascular syndromes, to improve care, and lay the foundation for future directions for research. PMID- 20582593 TI - My living history to pediatric neurosurgery. PMID- 20582590 TI - Bacterial diversity in the haloalkaline Lake Elmenteita, Kenya. AB - Lake Elmenteita is one of the alkaline saline lakes within the Kenyan Rift valley. The lake is situated on the floor of the Kenyan Rift Valley at 1,776 m above sea level and has no direct outlet. The microbial diversity of the lake was investigated using a culture-independent approach. Five different sampling points were selected randomly within the lake. Wet sediments and water samples were collected from each sampling point. In addition, dry mud cake was collected from three points where the lake had dried. DNA was extracted from the samples and the 16S rRNA genes amplified using universal primers for Bacteria. Thirteen clone libraries were constructed using the PCR amplified 16S rRNA genes. A total of 1,663 clones were picked. Representative clones were selected using ARDRA technique for sequencing. 655 partial and non-chimeric clone sequences indicated the presence of 37 orders in the Domain Bacteria. Cyanobacteria were the most abundant clones in terms of numbers whereas members of the phylum Firmicutes group were the second in terms of numbers but the most diverse in terms of genera represented. All clones affiliated to the class Betaproteobacteria originated from DNA obtained from the water samples. Analysis using BLAST showed that 93.1% of the sequenced clones had similarity values below 98% to both cultured and as yet uncultured bacteria, resulting in 596 phylotypes. Therefore, it can be concluded that Lake Elmenteita harbours phylogenetically diverse groups of bacteria involved in complex metabolic interactions within the Lake's ecosystem. PMID- 20582594 TI - One-year clinical outcomes with abciximab in acute myocardial infarction: results of the BRAVE-3 randomized trial. AB - PURPOSE: In the Bavarian Reperfusion Alternatives Evaluation (BRAVE)-3 study upstream administration of abciximab additional to 600 mg clopidogrel loading did not reduce the infarct size in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions. The aim of this study was to investigate 1-year clinical outcomes in the BRAVE-3 study patients. METHODS: A total of 800 patients with acute STEMI within 24 h from symptom onset, all treated with 600 mg of clopidogrel were randomized in a double-blind fashion to receive either abciximab (n = 401) or placebo (n = 399) in the intensive care unit before being sent to the catheterization laboratory. RESULTS: The main outcome of interest of the present study, the composite of death, recurrent myocardial infarction, stroke or revascularization of the infarct-related artery (IRA) at 1 year, was 23.0% (92 patients) in the abciximab versus 25.7% (102 patients) in the placebo group [relative risk (RR) = 0.90, 95% confidence interval (CI) 0.67-1.20; P = 0.46]. The combined incidence of death, recurrent myocardial infarction or stroke was 9.3% in the abciximab group versus 6.0% in the placebo group (RR = 1.55, 95% CI 0.93-2.58; P = 0.09). There was a significant reduction of the IRA revascularization with abciximab compared to placebo (16.3 vs. 22.3%, RR = 0.71, 95% CI 0.52-0.98; P = 0.04). CONCLUSION: In patients with STEMI, all receiving 600 mg clopidogrel, abciximab did not improve overall clinical outcomes at 1 year after primary coronary stenting. PMID- 20582596 TI - Cerebral computed tomography perfusion at the bedside using a portable CT scanner: report of two cases. PMID- 20582595 TI - Dendro[C(60)]fullerene DF-1 provides radioprotection to radiosensitive mammalian cells. AB - In this study, the ability of the C(60) fullerene derivative DF-1 to protect radiosensitive cells from the effects of high doses of gamma irradiation was examined. Earlier reports of DF-1's lack of toxicity in these cells were confirmed, and DF-1 was also observed to protect both human lymphocytes and rat intestinal crypt cells against radiation-induced cell death. We determined that DF-1 protected both cell types against radiation-induced DNA damage, as measured by inhibition of micronucleus formation. DF-1 also reduced the levels of reactive oxygen species in the crypt cells, a unique capability of fullerenes because of their enhanced reactivity toward electron-rich species. The ability of DF-1 to protect against the cytotoxic effects of radiation was comparable to that of amifostine, another ROS-scavenging radioprotector. Interestingly, localization of fluorescently labeled DF-1 in fibroblast was observed throughout the cell. Taken together, these results suggest that DF-1 provides powerful protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, and cell death. PMID- 20582597 TI - Biomechanical analysis of running in weightlessness on a treadmill equipped with a subject loading system. AB - One countermeasure used during long-duration spaceflight to maintain bone and muscle mass is a treadmill equipped with a subject loading system (SLS) that simulates gravity. To date, little is known about the biomechanics of running in weightlessness on such a treadmill-SLS system. We have designed an instrumented treadmill/force plate to compare the biomechanics of running in weightlessness to running on Earth. Gravity was simulated by two pneumatic pistons pulling downward on a subject's harness, with a force approximately equal to body weight on Earth. Four transducers, mounted under the treadmill, measured the three components of the reaction force exerted by the tread belt under the foot. A high-speed video camera recorded the movements of limb segments while the electromyography of the four lower limb muscles was registered. Experiments in weightlessness were conducted during the European Space Agency parabolic flight campaigns. Control experiments were performed on the same subjects on Earth. When running on the treadmill with an SLS, the bouncing mechanism of running is preserved. Depending on the speed of progression, the ground reaction forces, contact and aerial times, muscular work and bone stress differed by a maximum of +/- 5-15% during running on the treadmill with an SLS, as compared to that on Earth. The movements of the lower limb segments and the EMG patterns of the lower limb muscles were also comparable. Thus, the biomechanics of running on Earth can reasonably be duplicated in weightlessness using a treadmill with an SLS that generates a pull down force close to body weight on Earth. PMID- 20582598 TI - Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury. AB - PURPOSE: Primary graft dysfunction still represents a major challenge in liver transplantation. We herein studied in an isolated rat liver perfusion model whether a multidrug donor preconditioning (MDDP) can not only reduce but also completely prevent cold ischemia-reperfusion injury. METHODS: MDDP included curcumin, simvastatin, N-acetylcysteine, erythropoietin, pentoxyphylline, melatonin, glycine, and methylprednisolone. Postischemic reperfusion was performed after 24 h cold storage in histidine-tryptophan-ketoglutarate solution with 37 degrees C Krebs Henseleit bicarbonate buffer. RESULTS: Cold hepatic ischemia-reperfusion resulted in a massive K(+) release, protein loss, and aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase elevation. This was associated with increased malondialdehyde formation, enhanced tumor necrosis factor-alpha and interleukin-6 production, pronounced leukocytic tissue infiltration, and apoptotic cell death. CONCLUSIONS: MDDP abolished the inflammation response and was capable of completely preventing the manifestation of parenchymal injury. Thus, MDDP potentiates the protective effects reported after single-drug donor preconditioning and may therefore be an interesting approach to improve the outcome in clinical liver transplantation. PMID- 20582599 TI - Why so late?!--delay in treatment of colorectal cancer is socially determined. AB - PURPOSE: The interval between symptom onset and therapy in patients with colorectal cancer was studied. METHODS: One hundred twenty three patients with colorectal cancer were included. Demography data, symptoms, consultations, and tumour stage were obtained by standardized questionnaires. Risk factors for delayed treatment were analysed. RESULTS: Eighty six patients suffered from colonic cancer. The total time between the first symptoms and therapy ranged from 13 to 442 days (mean, 148). Delay of surgical therapy was responsible for significantly higher tumour grades. Delayed start of therapy was found to be correlated to the type of cancer, socioeconomic status, marital status, and quality of first consultation (univariate analysis). On multivariate analyses, type of cancer, marital and socioeconomic status remained significantly associated with delayed treatment (all p values <= 0.001, r(2) = 0.50). CONCLUSIONS: The delay in treatment of colorectal cancer depends on socioeconomic status and family background. Achieving equity in colorectal cancer detection may require consideration of high-risk subgroups. PMID- 20582600 TI - Uncinate process first--a novel approach for pancreatic head resection. AB - PURPOSE: Partial pancreatico-duodenectomy is the standard treatment for malignancies of the pancreatic head. We describe a technical modification with a retrograde dissection of the pancreatic head as a novel surgical approach. METHODS: Retrograde resection of the pancreatic head is performed starting with the uncinate process after division of the first jejunal loop and transection of the pancreas as the last operative step of the resection. Technical aspects and possible advantages for this procedure are discussed. RESULTS: The retrograde resection can be safely performed and offers a comfortable and innovative approach for pancreatico-duodenectomy. CONCLUSIONS: The "uncinate process first" approach can serve as an additional approach in modern pancreatic surgery. Further studies are required to evaluate this procedure regarding operative parameters and postoperative outcome compared to the standard resection. PMID- 20582601 TI - Primary closure versus T-tube drainage after common bile duct exploration for choledocholithiasis. AB - PURPOSE: The aim of this study was to evaluate the benefits and harms of primary closure versus T-tube drainage after common bile duct (CBD) exploration for choledocholithiasis. METHODS: A literature search of MEDLINE (PubMed), EMBASE, and the Cochrane Library was done to identify randomized controlled trials assessing the benefits and harms of primary closure versus T-tube drainage after CBD exploration from Jan. 1990 to Apr. 2010. A meta-analysis was set up to distinguish overall difference between the primary closure and the T-tube drainage group. RESULTS: There were statistically significant differences between groups: biliary complications (odds ratio (OR) 95% confidence interval (CI), 0.42 (0.19-0.92); P = 0.03), main complications (OR 95% CI, 0.46 (0.23-0.90); P = 0.02), operating time (weighted mean difference (WMD) 95% CI, -19.53 (-29.35 to 9.71); P < 0.0001), and hospital stay (WMD 95% CI, -4.16 (-7.07 to -1.24); P = 0.005) except peri-operative mortality (OR 95% CI, 0.83 (0.11-6.37); P = 0.86), residual stones (OR 95% CI, 0.70 (0.22-2.25); P = 0.55), and abdominal collections (OR 95% CI, 1.93 (0.34-10.76); P = 0.46). And the result of wound infection (OR 95% CI, 0.38 (0.14-1.02); P = 0.05) tended to favor the primary closure group. CONCLUSION: The primary closure might be as effective as T-tube drainage after choledochotomy in the prevention of the development of post operative complications. PMID- 20582602 TI - Oligosymptomatic vs. symptomatic incisional hernias--who benefits from open repair? AB - INTRODUCTION: Incisional hernias are one of the most often complications in abdominal surgery and therefore present a significant surgical and socioeconomic problem. To date, incisional hernias are always an indication for surgery, regardless of the patient's symptoms. However, it remains unclear to what extent the surgery actually results in symptomatic improvement and whether a relevant risk of incarceration exists. The purpose of this study was to investigate the motivation that led to incisional hernia repairs and whether patients benefit from surgery with regard to pain and subjective criteria. MATERIALS AND METHODS: This prospective study included patients who underwent open abdominal incisional hernia repair using mesh implantation. Data collection was done preoperatively and 6 months postoperatively. The intensity of pain was evaluated using the Numeric Analog Scale (NAS). Patients were divided according to their preoperative level of pain into oligosymptomatic (NAS 0-3) and symptomatic (NAS 4-10) groups, and the postoperative outcome of both groups was compared. RESULTS: Ninety patients were prospectively enrolled: 45 males (50.0%) and 45 females (50.0%); 43 patients (47.8%) were oligosymptomatic preoperatively, while 47 patients (52.2%) reported relevant pain. The most frequent motivation for surgery named by the oligosymptomatic patients was fear of incarceration (79.1%), while the symptomatic patients mostly mentioned pain (76.6%). At 6 months postoperatively, significantly more oligosymptomatic patients complained of relevant pain (p < 0.001). In the symptomatic patient group, there was a significant reduction in relevant pain (p < 0.001). At that time, the level of relevant pain was comparable in both groups (33.3% versus 35.6%). Seven of 87 patients (8.0%) experienced recurrence within 6 months. Three patients with acute incarceration were treated with emergency repair (3.2%). CONCLUSIONS: In patients with oligosymptomatic incisional hernias, fear of incarceration is the most frequent motivation for surgical treatment, even though the actual risk of incarceration seems to be rather low. If the incisional hernia causes relevant discomfort preoperatively, the surgery provides significant relief. In contrast, there is no improvement regarding pain in the oligosymptomatic patient group. This leads to the conclusion that, in the case of oligosymptomatic incisional hernias, the general indication for surgical revision should be viewed critically. PMID- 20582603 TI - Endotoxin elimination in sepsis: physiology and therapeutic application. AB - PURPOSE: The present review summarizes key papers on the elimination of endotoxin in human. RESULTS: Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and are involved in the pathogenesis of sepsis and septic shock. Elimination of LPS is vital; therefore, therapeutic detoxification of LPS may offer new perspectives. Multiple mechanisms eliminate LPS in human comprising molecules that bind LPS and prevent it from signaling, enzymes that degrade and detoxify LPS, processes that inactivate LPS following uptake into the reticulo-endothelial system, and mechanisms of adaptation that modify target cells responding to LPS. These mechanisms are powerful and detoxification capacity adapts as required. Results of therapeutic interventions aiming at the removal of LPS by medication (immunoglobulins) or extracorporeal means are controversial. At least in part, animal experiments revealed increased survival. Human trials confirmed the positive effects on parameters of secondary importance, but not on morbidity or survival which was attributed to the heterogeneity of patients suffering from consequences of severe infectious diseases and sepsis. CONCLUSION: The hypothesis of LPS-driven inflammatory processes remains very attractive. However, few therapeutic yet immature options have been developed to date. PMID- 20582604 TI - The role of pollen limitation on the coexistence of two dioecious, wind pollinated, closely related shrubs in a fluctuating environment. AB - Elucidating the mechanisms of species coexistence is a crucial goal in ecology. Theory suggests that, when resource abundance fluctuates, coexistence can be achieved if each species in a competing pair is better at exploiting resources at opposite extremes of a fluctuating resource spectrum. Nonetheless, the proximal mechanisms allowing coexistence remain largely unexplored. In a previous paper, we showed that the coexistence of two Atriplex species was facilitated by their varying demographic response (in survival, growth and recruitment) to fluctuation in water availability. Here we explore the effect of spatial distribution, and pollen and resource limitation on the reproductive success (production of viable seeds) of the same two species. An analysis of their spatial distribution showed that Atriplex acanthocarpa had a clumped distribution, which is thought to increase the effectiveness of pollination in wind-pollinated plants, while Atriplex canescens had a random distribution, a pattern expected to restrict wind pollination success. A pollen and resource (water and nutrients) addition experiment implemented through a repeated-measures design demonstrated that seed viability of A. canescens was both pollen and resource limited, but that these effects were negligible in A. acanthocarpa. Under natural conditions, pollen limitation restricted seed number in A. canescens to only one-third of that recorded when manual pollination was performed. By decreasing its fecundity (and consequent potential seedling recruitment), pollen limitation reverses the competitive advantage of A. canescens over A. acanthocarpa when the limiting resource (water) is abundant and seedling recruitment takes place. To our knowledge, our study of this congeneric pair in the Chihuahuan Desert is the first to document a link between pollen limitation and species coexistence. PMID- 20582605 TI - Identification of RNA regions that determine temperature sensitivities in betanodaviruses. AB - Betanodaviruses, the causative agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNA genomes. The larger genomic segment, RNA1 (~3.1 kb), encodes an RNA-dependent RNA polymerase (protein A), and the smaller genomic segment RNA2 (~1.4 kb) codes for the coat protein. These viruses can be classified into four genotypes, designated striped jack nervous necrosis virus (SJNNV), redspotted grouper nervous necrosis virus (RGNNV), tiger puffer nervous necrosis virus (TPNNV), and barfin flounder nervous necrosis virus (BFNNV), based on similarities in their partial RNA2 sequences. The optimal temperatures for the growth of these viruses are 20-25 degrees C (SJNNV), 25-30 degrees C (RGNNV), 20 degrees C (TPNNV), and 15-20 degrees C (BFNNV). However, little is known about the mechanisms underlying the temperature sensitivity of these viruses. We first constructed two reassortants between SJNNV and RGNNV to test their temperature sensitivity. The levels of viral growth and RNA replication of these reassortants and parental viruses in cultured fish cells were similar at 25 degrees C. However, the levels of all of the viruses but RGNNV were markedly reduced at 30 degrees C. These results indicate that both RNA1 and RNA2 control the temperature sensitivity of betanodaviruses by modulating RNA replication or earlier viral growth processes. We then constructed ten mutated RGNNVs, the RNA1 segments of which were chimeric between SJNNV and RGNNV, and showed that only chimeric viruses bearing the RGNNV RNA1 region, encoding amino acid residues 1-445, grew similarly to the parental RGNNV at 30 degrees C. This portion of protein A is known to serve as a mitochondrial-targeting signal rather than functioning as an enzymatic domain. PMID- 20582606 TI - Immunomodulatory activities of a new pentapeptide (Bursopentin) from the chicken bursa of Fabricius. AB - The bursa of Fabricius (BF) is a central immune organ in birds, and some peptides from chicken BF have demonstrated important immune functions. Here, a new 626.27 Da pentapeptide, Bursopentin (BP5, Cys-Lys-Arg-Val-Tyr) was isolated and purified by reverse-phase high-performance liquid chromatography. In this study, we examined the effects of BP5 on antigen-specific immune response in BALB/c mice sensitized with inactivated avian influenza virus (AIV) [A/Duck/Jiangsu/NJ08/05 (AIV H9N2 subtype)]. The results suggested that BP5 enhanced anti-hemagglutinin antibody (IgG, the isotypes IgG1 and IgG2a) production, induced both of Th1- (IL 2 and IFN-gamma) and Th2-type (IL-4 and -10) cytokines, increased proliferations of splenic lymphocyte subsets CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+) and B cells, and enhanced cytotoxic T-lymphocyte activity of the activated splenocytes against NIH3T3 cells. The effects of BP5 on the proliferation of isolated T- and/or B-cell populations of BALB/c mice were assessed, and the data suggested that BP5 promoted spleen lymphocyte proliferation by activating B cells directly and T cells indirectly. Further analysis revealed that B-lymphocyte proliferation induced by BP5 is mediated by reactive oxygen species generated from thiol auto-oxidation of BP5. Furthermore, our data indicated that protein kinase C, mitogen-activated protein kinase, and nuclear factor kappa B are involved in the signal transductions during the BP5-induced B lymphocyte proliferation. This study indicates that BP5 could be a potential immunomodulator for future immuno-pharmacological use. PMID- 20582607 TI - Why OppA protein can bind sequence-independent peptides? A combination of QM/MM, PB/SA, and structure-based QSAR analyses. AB - Periplasmic oligopeptide-binding protein (OppA) is the initial receptor in the ATP-binding cassette (ABC) system of bacteria, which exhibits a broad specificity in binding oligopeptides without regard to sequence. Here, we present a computational study on the structural properties and energetic landscapes of OppA protein interacting with its cognate ligands on the basis of 28 structure/affinity-known OppA-tripeptide complexes. By employing a well-designed protocol that couples the hybrid quantum mechanical/molecular mechanical (QM/MM) scheme and the sophisticated Poisson-Boltzmann/surface area (PB/SA) solvent model together to analyze and decompose the energy components associated with the OppA peptide binding, we demonstrate that the broad specificity of OppA-recognizing peptides is originated from a series of exquisite balances between the free energy contributions from, for example, the direct nonbonded interactions and indirect desolvation effects, the main chains and side chains, and the different residue positions of the tripeptide ligands. We also show that, in a framework of structure-based quantitative structure-activity relationship (SB-QSAR) methodology, the QM/MM-PB/SA-derived energy terms could be used as a good descriptor to characterize the interaction profile of OppA with peptides and correlate pretty well with the experimentally measured affinities of the binding. PMID- 20582608 TI - A typically atypical tenosynovitis. AB - A 68-year-old woman developed tenosynovitis of the right second digit without a history of injury or animal bites. Apart from high titer anti-nuclear antibodies, serological studies were unremarkable. Tuberculin test and interferon gamma release assay were both negative. Several immunosuppressive therapies led only to partial relief of symptoms. Of note, clinical symptoms worsened significantly after introduction of adalimumab therapy. Tenosynovectomy was performed revealing a granulomatous inflammatory process. Seven weeks later, Mycobacterium malmoense could be cultured from the surgical specimen. A four drug antibiotic regimen was started and immunosuppressive therapy discontinued resulting in complete clinical remission. Our case highlights non-tuberculous mycobacterial (NTM) tenosynovitis as an important differential diagnosis of atypical arthritis. A negative tuberculin skin test as well as negative Ziehl-Neelsen stain does not argue against NTM infection. In fact, mycobacterial culture for extended periods remains the gold standard for diagnosis. PMID- 20582609 TI - Study of the direct bactericidal effect of Nd:YAG and diode laser parameters used in endodontics on pigmented and nonpigmented bacteria. AB - Laser light can be used during endodontic procedures to sterilize the root canal by destroying bacteria. Previous in-vitro studies that investigated the mechanism of the destruction of bacteria inhabiting the root canal by 1,064-nm Nd:YAG and 808-nm diode laser light used substrates that absorb light in the near-infrared (NIR) spectrum. These substrates heat the bacterial microenvironment, which possibly contributes to cell death. To determine the direct effect of laser light on the bacterial sample in the absence of detrimental heating, a sapphire substrate, which is virtually transparent in NIR spectrum, was inoculated with bacterial samples and subjected to laser irradiation at 1,064 nm (1.5 W, 15 Hz) and at 808 nm (1.5 W, 20 Hz). Enterococcus faecalis, Escherichia coli, and Porphyromonas gingivalis bacteria were used. E. faecalis and E. coli were largely unaffected by laser light. The viability of P. gingivalis, a pigmented bacterium, was directly affected by both NIR wavelengths (a 57% decrease of viability at 1,064 nm and a 31% decrease at 808 nm). Our results indicate that the primary mediator of cell death appears to be the interaction between NIR laser light and the bacterial microenvironment, most likely in the form of heating. Our research suggests that when optimizing the efficacy of laser-assisted endodontic sterilization of the root canal, the optical characteristics of the bacterial microenvironment play a key role, as nonpigmented bacteria appear to be virtually transparent at 808 nm and 1,064 nm. PMID- 20582610 TI - Long-term effects of a single application of a water-cooled pulsed Nd:YAG laser in supplement to scaling and root planing in patients with periodontal inflammation. AB - The aim of this work was to investigate the long-term effects of a single application of a water-cooled pulsed neodymium yttrium aluminium garnet (Nd:YAG) laser, in combination with scaling and root planing (SRP) for the treatment of periodontal inflammation. Twenty-two patients were included in this split-mouth single blind randomized controlled clinical trial. The parameters of the air and water-cooled Nd:YAG laser were: 4 W, 80 mJ/pulse, 50 Hz and a pulse width of 350 MUs. The "test side" was treated with a single application of Nd:YAG laser and SRP; while the "control side " was treated with SRP alone. At baseline, and after a median follow-up time of 20 months (range 12-39), periodontal inflammatory parameters (plaque index [PI], gingival index [GI], probing pocket depth [PPD]), and marginal bone loss (on digital bite-wing radiographs) were measured. Gingival crevicular fluid (GCF) was collected from the teeth 35, 36, 45, and 46 at baseline and at follow-up. Pl (p < 0.01), GI (p < 0.01), and PPD (p < 0.001) were significantly lower on the test side compared to the control side at follow-up. Radiological results showed significantly less bone loss on the test side compared to the control side (p < 0.05). GCF volume was lower on the test side compared to the control side (p < 0.01). In conclusion, a single application of Nd:YAG laser in combination with SRP had a positive long-term effect on periodontal health compared to treatment by SRP alone. PMID- 20582611 TI - Musculoskeletal: what's different in children? Pain and limping. PMID- 20582612 TI - An analytical solution for the radial and tangential displacements on a thin hemispherical layer of articular cartilage. AB - A simplified analytical solution has been obtained for the radial and tangential displacements on the surface of a thin, hemispherical layer of porous-elastic articular cartilage firmly bonded to a rigid foundation. A static pressure distributed according to a paraboloid of revolution is applied simulating cartilage compression by a porous indenter. The solution method is in the form of an asymptotic series and uses Laplace transforms. The analytical predictions are in qualitative agreement with the behaviour of biphasic articular cartilage reported in the literature. A direct comparison with numerical simulations using commercially available Finite Element Modelling (FEM) software was also carried out for conditions relevant to natural hip joints and the results show a good quantitative agreement overall. PMID- 20582613 TI - SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinase of the human malaria parasite Plasmodium falciparum. AB - Over the last decade, several protein kinases inhibitors have reached the market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. The functions of the majority of protein kinases of Plasmodium falciparum, the parasitic protist responsible for the most virulent form of human malaria, remain unknown. Here we present a thorough characterisation of PfTKL3 (PF13_0258), an enzyme that belongs to the tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics that PfTKL3 is essential for asexual parasite proliferation in human erythrocytes. PfTKL3 is expressed in both asexual and gametocytes stages, and in the latter the protein co-localises with cytoskeleton microtubules. Recombinant PfTKL3 displays in vitro autophosphorylation activity and is able to phosphorylate exogenous substrates, and both activities are dramatically dependent on the presence of an N-terminal "sterile alpha-motif" domain. This study identifies PfTKL3 as a validated drug target amenable to high-throughput screening. PMID- 20582614 TI - Enzyme replacement therapy for Morquio A: an active recombinant N acetylgalactosamine-6-sulfate sulfatase produced in Escherichia coli BL21. AB - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency. Currently no effective therapies exist for MPS IVA. In this work, production of a recombinant GALNS enzyme (rGALNS) in Escherichia coli BL21 strain was studied. At shake scale, the effect of glucose concentration on microorganism growth, and microorganism culture and induction times on rGALNS production were evaluated. At bench scale, the effect of aeration and agitation on microorganism growth, and culture and induction times were evaluated. The highest enzyme activity levels at shake scale were observed in 12 h culture after 2-4 h induction. At bench scale the highest enzyme activity levels were observed after 2 h induction. rGALNS amounts in inclusion bodies fraction were up to 17-fold higher than those observed in the soluble fraction. However, the highest levels of active enzyme were found in the soluble fraction. Western blot analysis showed the presence of a 50-kDa band, in both soluble and inclusion bodies fractions. These results show for the first time the feasibility and potential of production of active rGALNS in a prokaryotic system for development of enzyme replacement therapy for MPS IVA disease. PMID- 20582615 TI - Spontaneous acute subdural hematoma as the initial manifestation of chronic myeloid leukemia. AB - Spontaneous acute subdural hematoma is rare and limited to sporadic case reports, associated with neoplasm, aneurysm, arteriovenous malformation and cocaine use. Subdural hematoma has also been reported in association with leukemic malignancies, either during therapy or after diagnosis. However, there are no reports of spontaneous acute subdural hematoma as the primary initial presenting manifestation of a chronic myeloid leukemia. Here we describe one case of a 53 year-old male that presented with severe right-sided headache and intermittent left-sided paresthesias. CT scan showed non-traumatic right-sided acute subdural hematoma. Further evaluation revealed that the patient had chronic myeloid leukemia. His peripheral white blood count normalized after Gleevec and hydroxyurea chemotherapy. Furthermore, he had no neurological deficits after his subdural collection was adequately evacuated. PMID- 20582616 TI - Cadmium and transport of ions and substances across cell membranes and epithelia. AB - Toxic metals such as cadmium (Cd(2+)) pose serious risks to human health. However, even though the importance of Cd(2+) as environmental health hazards is now widely appreciated, the specific mechanisms by which it produces its adverse effects have yet to be fully elucidated. Cd(2+) is known to enter cells, it binds and interacts with a multitude of molecules, it may indirectly induce oxidative stress and interfere with gene expression and repair of DNA. It also interacts with transport across cell membranes and epithelia and may therefore disturb the cell's homeostasis and function. Interaction with epithelial transport, especially in the kidney and the liver, may have serious consequences in general health. A lot of research still needs to be done to understand the exact way in which Cd(2+) interferes with these transport phenomena. It is not always clear whether Cd(2+) has primary or secondary effects on cell membrane transport. In the present review we try to summarize the work that has been done up to now and to critically discuss the relevance of the experimental work in vitro with respect to the in vivo situation. PMID- 20582617 TI - Mycelial cultivation of Phellinus linteus using cheese-processing waste and optimization of bioconversion conditions. AB - A medicinal mushroom, Phellinus linteus, was successfully cultivated using a cheese-processing waste, whey, and the optimal bioconversion conditions for the maximum mycelial growth rate was also estimated through solid-state cultivation experiments. Response surface analysis with a face-centered design (center point replication = 5) was applied to statistically approximate the simultaneous effects of the three variables, i.e., substrate concentration (10-30 g lactose l 1), temperature (20-30 degrees C), and pH (4-6), on the mycelial growth rate of P. linteus. The following is a partial cubic model where eta is the mycelial growth rate (K(r)) and x(k) is the corresponding variable term (k = substrate concentration, temperature, and pH in order): eta = -23.8 + 8.67 * 10-2 x1 + 1.48x2 + 1.77x3 + 8.00 * 10-4 x1x2 + 7.25 * 10-2 x1x3 + 5.13 * 10-2 x2x3 -1.28 * 10-2 x12 -3.18 * 10-2 x22. -2.64 * 10-1 x32 -3.28 * 10-3 x1x2 x3 + 4.68 * 10-4 x12x2. The produced response surface model proved to be significant (r2 > 0.99, P value <0.0001, coefficient of variation <5%) to describe the explored space. Temperature was found to be the most significant factor of dominant effects on the mycelial growth rate, and other variables such as temperature2, pH, pH2, and (substrate concentration2 * temperature) also showed significant effects on the model output. The maximum mycelial growth rate was predicted to be 2.80 mm d-1 at 29.7 g lactose l-1, 26.2 degrees C, and pH 5. Our results proved a good potential of whey to serve as an alternative growth medium for cultivating P. linteus mycelia. This may provide another potential for managing this nutrient-rich waste in a cost-effective way. PMID- 20582618 TI - Biodegradation of 2-nitrotoluene by Micrococcus sp. strain SMN-1. AB - A bacterial consortium capable of degrading nitroaromatic compounds was isolated from pesticide-contaminated soil samples by selective enrichment on 2 nitrotoluene as a sole source of carbon and energy. The three different bacterial isolates obtained from bacterial consortium were identified as Bacillus sp. (A and C), Bacillus flexus (B) and Micrococcus sp. (D) on the basis of their morphological and biochemical characteristics and by phylogenetic analysis based on 16S rRNA gene sequences. The pathway for the degradation of 2-nitrotoluene by Micrococcus sp. strain SMN-1 was elucidated by the isolation and identification of metabolites, growth and enzymatic studies. The organism degraded 2 nitrotoluene through 3-methylcatechol by a meta-cleavage pathway, with release of nitrite. PMID- 20582620 TI - Towards the development of hemerythrin-based blood substitutes. AB - Hemerythrin is proposed as an alternative to hemoglobin-based blood substitutes. In contrast to hemoglobin, hemerythrin exhibits negligible reactivity towards oxidative and nitrosative stress agents (peroxide, nitric oxide, nitrite). Protocols for attachment of polyethylene glycol and glutaraldehyde cross-linking of Hr are described. These derivatizations appear to have favorable effects on O(2) affinity and autoxidation rates for use in blood substitutes. Based on lessons learned from hemoglobin-based blood substitutes, these derivatizations should also help limit extravasation and antigenicity of a hemerythrin-based blood substitute. PMID- 20582621 TI - Ethnic-racial socialization and adjustment among Latino college students: the mediating roles of ethnic centrality, public regard, and perceived barriers to opportunity. AB - Parents' efforts to socialize their children around issues of ethnicity and race have implications for well-being in several life domains, including academic and psychological adjustment. The present study tested a multiple mediator model in which parental ethnic-racial socialization was linked to psychological adjustment through two dimensions of ethnic identity (ethnic centrality and public regard) as well as two types of perceived barriers to opportunity (language and economic). Data were drawn from a sample of Latino students (N = 227; 65% women) attending a highly selective university. Results suggest that cultural socialization was related to self-esteem, depressive symptoms, and physical symptoms, and that part of its association with self-esteem was mediated by ethnic centrality beliefs. In contrast, preparation for bias had few direct associations with adjustment in this sample; this type of ethnic-racial socialization primarily functioned through its association with public regard and perceived language barriers to upward mobility. Moreover, in predicting self esteem, public regard and perceived language barriers exhibited equally important roles as mediators of preparation for bias. These findings extend previous research, and implications for future research on ethnic-racial socialization among Latinos are discussed. PMID- 20582622 TI - Racial/ethnic socialization and parental involvement in education as predictors of cognitive ability and achievement in African American children. AB - Racial/ethnic socialization has not been studied in the context of other parenting behaviors such as parental involvement in education and its relationship to children's cognitive outcomes. The present study tested the impact of racial/ethnic socialization and parental involvement in education on cognitive ability and achievement in a sample of African American youth. Two dimensions of racial/ethnic socialization, cultural exposure (i.e., exposure to diverse cultures) and cultural socialization (i.e., in-group pride), were examined in a sample of 92 African American mother-child dyads, of which 50% were female. Maternal reports of involvement during their child's 5th grade year were examined as a moderator in the relationship between racial/ethnic socialization and cognitive ability and achievement. Hierarchical regression analyses revealed that mothers' reports of cultural exposure messages measured in 4th grade predicted children's scores on 5th grade assessments of passage comprehension. There was also a significant interaction indicating that greater cultural exposure and more parental involvement in education predicted better reading passage comprehension scores over time. The implications for assessing dimensions relevant to cognitive ability and achievement in African American children are discussed. PMID- 20582623 TI - Genes or culture: are mitochondrial genes associated with tool use in bottlenose dolphins (Tursiops sp.)? AB - Some bottlenose dolphins use marine sponges as foraging tools ('sponging'), which appears to be socially transmitted from mothers mainly to their female offspring. Yet, explanations alternative to social transmission have been proposed. Firstly, the propensity to engage in sponging might be due to differences in diving ability caused by variation of mitochondrial genes coding for proteins of the respiratory chain. Secondly, the cultural technique of sponging may have selected for changes in these same genes (or other autosomal ones) among its possessors. We tested whether sponging can be predicted by mitochondrial coding genes and whether these genes are under selection. In 29 spongers and 54 non-spongers from two study sites, the non-coding haplotype at the HVRI locus was a significant predictor of sponging, whereas the coding mitochondrial genes were not. There was no evidence of selection in the investigated genes. Our study shows that mitochondrial gene variation is unlikely to be a viable alternative to cultural transmission as a primary driver of tool use in dolphins. PMID- 20582625 TI - Discussion of "Bayesian local influence for survival models" by Ibrahim, Zhu and Tang. PMID- 20582624 TI - Natural factors to consider when using acetylcholinesterase activity as neurotoxicity biomarker in Young-Of-Year striped bass (Morone saxatilis). AB - Acetylcholinesterase (AChE) activity is one of the most common biomarkers of neurotoxicity used in aquatic organisms. However, compared to its extensive use as biomarker, the effects of natural factors on AChE activity remain unclear especially in estuarine fishes. The aim of this study was to evaluate the effects of natural factors on AChE activity of striped bass (Morone saxatilis) juveniles. Brain AChE activity was measured in YOY (Young-Of-Year) individuals collected monthly from August 2007 to January 2008 at 12 different sites in the San Francisco Estuary system. The spatio-temporal variability of AChE was analyzed relative to water temperature and salinity as well as fish size. AChE activity was highly positively correlated with water temperature and to a lesser extent negatively with fish size while no relationship was detected with salinity. Taking into account these natural factors when using AChE as a biomarker will help to determine and understand the effects of neurotoxic contaminants on fish in estuarine systems. PMID- 20582626 TI - Gene transfer into Solanum tuberosum via Rhizobium spp. AB - Agrobacterium tumefaciens-mediated transformation (ATMT) is the preferred technique for gene transfer into crops. A major disadvantage of the technology remains the complexity of the patent landscape that surrounds ATMT which restricts its use for commercial applications. An alternative system has been described (Broothaerts et al. in Nature 433:629-633, 2005) detailing the propensity of three rhizobia to transform the model crop Arabidopsis thaliana, the non-food crop Nicotiana tabacum and, at a very low frequency, the monocotyledonous crop Oryza sativa. In this report we describe for the first time the genetic transformation of Solanum tuberosum using the non-Agrobacterium species Sinorhizobium meliloti, Rhizobium sp. NGR234 and Mesorhizobium loti. This was achieved by combining an optimal bacterium and host co-cultivation period with a low antibiotic regime during the callus and shoot induction stages. Using this optimized protocol the transformation frequency (calculated as % of shoots equipped with root systems with the ability to grow in rooting media supplemented with 25 MUg/ml hygromycin) of the rhizobia strains was calculated at 4.72, 5.85 and 1.86% for S. meliloti, R. sp. NGR234 and M. loti respectively, compared to 47.6% for the A. tumefaciens control. Stable transgene integration and expression was confirmed via southern hybridisation, quantitative PCR analysis and histochemical screening of both leaf and/or tuber tissue. In light of the rapid advances in potato genomics, combined with the sequencing of the potato genome, the ability of alternative bacteria species to genetically transform this major food crop will provide a novel resource to the Solanaceae community as it continues to develop potato as both a food and non-food crop. PMID- 20582627 TI - Suitability of the clonal marbled crayfish for biogerontological research: a review and perspective, with remarks on some further crustaceans. AB - This article examines the suitability of the parthenogenetic marbled crayfish for research on ageing and longevity. The marbled crayfish is an emerging laboratory model for development, epigenetics and toxicology that produces up to 400 genetically identical siblings per batch. It is easily cultured, has an adult size of 4-9 cm, a generation time of 6-7 months and a life span of 2-3 years. Experimental data and biological peculiarities like isogenicity, direct development, indeterminate growth, high regeneration capacity and negligible senescence suggest that the marbled crayfish is particularly suitable to investigate the dependency of ageing and longevity from non-genetic factors such as stochastic developmental variation, allocation of metabolic resources, damage and repair, caloric restriction and social stress. It is also well applicable to examine alterations of the epigenetic code with increasing age and to identify mechanisms that keep stem cells active until old age. As a representative of the sparsely investigated crustaceans and of animals with indeterminate growth and extended brood care the marbled crayfish may even contribute to evolutionary theories of ageing and longevity. Some relatives are recommended as substitutes for investigation of topics, for which the marbled crayfish is less suitable like genetics of ageing and achievement of life spans of decades under conditions of low food and low temperature. Research on ageing in the marbled crayfish and its relatives is of practical relevance for crustacean fisheries and aquaculture and may offer starting points for the development of novel anti-ageing interventions in humans. PMID- 20582628 TI - Why does ADHD confer risk for cigarette smoking? A review of psychosocial mechanisms. AB - Research has documented that adolescents and young adults with attention deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking, but less attention has examined why this risk exists. The current paper reviews the literature on different psychosocial mechanisms [self-medication hypothesis, social factors (social modeling, social impairments), cognitive factors (attitudes, coping skills), and psychological variables (ADHD symptom dimensions, comorbidity)] that might explain this increased smoking risk. Results of the review suggest that, while the self-medication hypothesis has some theoretical merit, it has not been adequately examined among adolescents and young adults with ADHD. Further, cognitive and social factors may be important mechanisms that help to explain the association between ADHD and cigarette smoking, but research in these areas is sparse. Finally, a larger body of literature suggests that different psychological aspects of ADHD (e.g., comorbidity, symptom dimensions) are related to smoking. Interpretation of findings of many of these studies was hindered due to significant methodological problems and the lack of a guiding theoretical orientation. Potential theories that might facilitate future work in this area are discussed. Future research should continue to explore these important psychosocial mechanisms as well as gene-environment interactions in examining the link between ADHD and cigarette smoking. PMID- 20582629 TI - Operational fidelity to an evidence-based HIV prevention intervention for people living with HIV/AIDS. AB - Evidence-based interventions are often disseminated in public health education with little known about their operational fidelity. This study examined the delivery of intervention components (operational fidelity) of a widely disseminated HIV prevention program designed for people living with HIV/AIDS named Healthy Relationships. Two hundred ninety-nine agencies that had been trained in the intervention by the Centers for Disease Control and Prevention were contacted, and 122 (41%) completed confidential interviews. Among the 93 agencies that implemented the program, 39 (40%) adapted at least one core element activity, and 21 (23%) dropped an activity. Most adaptations were intended to improve the community fit of the intervention. Agencies believed that funders demand that they implement the intervention with fidelity. Models of technology transfer that emphasize behavior change processes rather than specific curriculum content may advance prevention program dissemination. PMID- 20582630 TI - Fusarium verticillioides: evaluation of fumonisin production and effect of fungicides on in vitro inhibition of mycelial growth. AB - The objectives of this study were to evaluate the fumonisin production by 16 F. verticillioides strains on corn cultures and the effect of quintozene and fludioxonil + metalaxyl-M fungicides on "in vitro" mycelial growth on agar. In addition, the effect of fludioxonil + metalaxyl-M on fumonisin production in defined liquid culture medium was analyzed. Fumonisin B(1) levels on corn cultures ranged from 2.41 to 3996.36 MUg/g and the F. verticillioides 103F strain produced the highest level (3996.36 +/- 390.49 MUg/g, P < 0.05). F. verticillioides strains were inoculated in potato dextrose agar with the addition of quintozene (75 to 9,375 MUg/ml) and fludioxonil + metalaxyl-M (1.5 + 0.6 to 187.5 + 75 MUg/ml) in order to evaluate the effect of these fungicides on "in vitro" mycelial growth. The F. verticillioides strains showed great variability concerning ED(50) values, which were below the recommended application dose for quintozene, but above that for fludioxonil + metalaxyl-M. Moreover, fungicide addition to the culture medium increased mean FB(1) levels compared to the control, suggesting the importance of focusing on the effect of fungicides on mycotoxin production as well as on the phytopathogen control. PMID- 20582631 TI - Occurrence of different species of fusarium from wheat in relation to disease levels predicted by a weather-based model in Argentina pampas region. AB - Fusarium head blight (FHB) is an important disease throughout many of the world wheat-growing areas that have humid to semi-humid climate. The infection happens mainly during the anthesis of the wheat, when there have been favorable conditions of moisture and temperature. The direct relation of the infection to environmental factors makes possible the formulation of mathematical models that predict the disease. The causal agent of the FHB of the spike of wheat is attributed principally to Fusarium graminearum. High economic losses due yield decrease have been recorded in Argentina. In the present work, 67 isolates of Fusarium spp. were obtained from samples of wheat grains from Pampas region from 15 locations distributed in Buenos Aires, Entre Rios, Santa Fe and Corboba provinces during 2006 and 2007 wheat-growing seasons. The identification of species from monosporic isolates was carried out by morphological characterization and use of species-specific PCR-based assays. Both identification criteria were necessary and complementary for the species determination, since in some cases the molecular identification was not specific. Scanty presence of F. graminearum was observed in 2006 wheat-growing season coinciding with the lack of favorable meteorological conditions for producing FHB infection events. High presence of F. graminearum isolates was observed in 2007 wheat-growing season, in accordance with moderate incidence of the disease according to spatial distribution of FHB incidence values. The aim of this report was to identify the causal agent of the FHB disease by different taxonomic criteria and to relate its occurrence with disease incidence values predicted by a weather-based model in Argentina. PMID- 20582632 TI - Association between gap junction protein-alpha 8 polymorphisms and age-related cataract. AB - GJA8 plays an important role in lens growth and transparency. Therefore, we hypothesized that two single nucleotide polymorphisms (SNPs) in GJA8 might be associated with age-related cataract. We investigated the SNPs rs1495960 and rs9437983 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, in 96 age-related cataract patients, and 208 gender- and age-matched healthy controls. No significant differences between cases and controls were seen in genotype or allele distributions of rs1495960 (P > 0.05). The allele distribution of rs9437983 was different between cases and controls, but no difference was detected in its genotype distribution. Cataract patients had a significantly lower G-G haplotype frequency (4.9% vs. 15.5%, P = 0.0001), and a significantly higher G-A haplotype frequency (45.6% vs. 36.4%, P = 0.030) than controls. Limiting to nuclear cataract cases significantly increased the differences between cases and controls for G-G and G-A haplotypes. These results support that the GJA8 gene may be a novel susceptibility gene for age-related cataracts. PMID- 20582633 TI - Polymorphisms of MRF4 and H-FABP genes association with growth traits in Qinchuan cattle and related hybrids. AB - PCR-RFLP was applied to analyse polymorphisms within the MRF4 and heart fatty acid-binding protein (H-FABP) gene for correlation studies with growth traits in three-month-old Qinchuan (QQ), Qinchuan * Limousin (LQ) and Qinchuan * Red Angus (AQ) cattle. The results showed that 874 bp PCR products of MRF4 digested with XbaI and 2,075 bp PCR products of H-FABP digested with HaeIII were polymorphic in the three populations. Moreover, the frequencies of allele A at MRF4 locus and allele B at H-FABP locus in the QQ, AQ, and LQ populations were 0.8358/0.8888/0.8273 and 0.8358/0.7500/0.8195 respectively. Allele A at MRF4 locus and allele B at H-FABP locus were dominant in the three populations. No statistically significant differences in growth traits were observed among the genotypes of the all three populations at H-FABP locus. However, the association of MRF4 polymorphism with growth traits was then determined in all three populations. The body weight, withers height, heart girth and height at hip cross of individuals with genotype AA were higher than those with genotype AB or BB (P < 0.05). Therefore, we suggest that the MRF4 gene may function in the control or expression of growth traits, particularly body weight, withers height, heart girth and height at hip cross. PMID- 20582634 TI - An experimental research on chronic intermittent hypoxia leading to liver injury. AB - PURPOSE: Sleep apnea-hypopnea syndrome and its chronic intermittent hypoxia component may cause multi-system-targeted injury. The latest finding shows that liver is one of the injured organs. The purpose of the study is to observe the dynamic process of the influence that chronic intermittent hypoxia plays on rat liver enzyme, hepatic histology, and ultrastructure based on lipid disorders. METHODS: A total of 72 male Wistar rats were randomly divided into three groups. The control group was fed with a regular chow diet, the high fat group with a high fat diet, and the high fat plus intermittent hypoxia group with a high fat diet with a 7-h/day intermittent hypoxia treatment. Changes were observed in rat liver enzyme, hepatic histology, and ultrastructure of the three groups on the third, sixth, and ninth weeks, respectively. The liver paraffin sections were detected with myeloperoxidase. RESULTS: The liver function and structure of the control group were found to be normal; the liver enzyme level of the high fat group was significantly higher than that of the control group on the sixth and ninth weeks; and the liver enzyme level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group on the third, sixth, and ninth weeks (all P < 0.01). Observed by a light microscope and a transmission electron microscope, the high fat group and the high fat plus intermittent hypoxia group were all characterized by nonalcoholic fatty liver disease: the high fat group was characterized by simple fatty liver on the third and sixth weeks and by steatohepatitis on the ninth week; the damage of the high fat plus intermittent hypoxia group was significantly more severe than that of the high fat group in all the monitoring points, characterized by steatohepatitis on the sixth week and by obvious liver fibrosis on the ninth week; the myeloperoxidase level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group (all P < 0.01). CONCLUSIONS: Under the conditions of high fat and intermittent hypoxia, the injury to the liver function, hepatic histology, and ultrastructure is more severe than that of the high fat group. The injury mainly was characterized by nonalcoholic fatty liver disease and becomes more severe with increased exposure time. Oxidative stress may play an important role in the mechanism. PMID- 20582635 TI - Monuments as sampling surfaces of recent traffic pollution. AB - BACKGROUND, AIM AND SCOPE: A new approach towards monuments, considering them as a passive sampler of pollution, is presented. Cultural Heritage objects suffer daily the damages of environmental pollution, especially in those areas interested by heavy traffic. Since monuments undergo only periodic conservation or maintenance works, surfaces are able to accumulate atmospheric deposit and to record changes in its composition. An optimised analytical protocol was developed in order to quantify platinum and rhodium at trace level on surfaces. The two elements have become tracers of automobile emissions in recent years, since the introduction of catalytic converters, and could have catalytic effects on the decay reactions of natural and artificial stone materials. As a first case study, the cement mortar surfaces of a twentieth century monument, the Camerlata Fountain, in Como (Italy) were investigated. MATERIALS AND METHODS: The surfaces of the monument were scraped in areas both exposed to atmosphere and sheltered by the architectural elements of the building. The powders were dissolved by microwave-assisted mineralisation with a solution of HCl and HNO(3). The solution was filtered, irradiated and analysed by adsorptive cathodic stripping voltammetry. The powders were also analysed by infrared spectroscopy and X-ray diffraction in order to determine the chemical and mineralogical composition. RESULTS AND DISCUSSION: An analysis protocol was set up considering the matrix effect and the expected low concentrations of the two metals. The results enlightened variable concentration values and distribution areas of platinum (0.013-45 MUg/kg) and rhodium (0.55-274.4 MUg/kg), suggesting the ability of artificial stone surfaces to accumulate the two elements. The sample chemical and mineralogical composition was consistent with a typical cement plaster interested by decay phenomena. CONCLUSIONS: This work investigated the relation between Cultural Heritage and pollution by another point of view. The analytical protocol presented in this paper was effective in determining platinum and rhodium in traces on the investigated stone surfaces with negligible matrix effects. RECOMMENDATION AND PERSPECTIVES: The presence of platinum and rhodium on monument surfaces should be of significant interest when planning Cultural Heritage conservation. A better knowledge of the role of the two metals in decay phenomena could impact in a positive way artwork conservation. PMID- 20582636 TI - Manganese in the urban atmosphere: identifying anomalous concentrations and sources. AB - PURPOSE: Industrial emissions can raise urban background levels of inhalable Mn particles in an order of magnitude above normal, eclipsing the contribution made by natural sources and traffic. METHODS: The source of such emissions can be identified using a multidisciplinary approach which integrates ICP-MS chemical analyses of PM(10) and PM(2.5) samples with positive matrix factorization source apportionment modelling, scanning electron microscopy and meteorological data. RESULTS: We apply this methodology to data from Santander (N Spain), where morning Mn-bearing industrial contamination sourcing from the SW is returned towards the city by afternoon NE sea breezes. This wind direction reversal carries the industrial pollution plume inland, detectably raising urban background levels of MnPM(10) in the town of Torrelavega 20 km away. Industrially sourced daily urban background Mn levels at Santander reach >1,000 ng/m(3), average >150 ng/m(3). CONCLUSIONS: We demonstrate the anomalous nature of such concentrations by comparing them with >2,500 PM(10) chemical analyses of ambient PM(10) from other sites in Spain which show how current background Mn levels in urban air typically average only 10 ng/m(3), rising to 20-25 ng/m(3) in city traffic sites. Daily levels of atmospheric Mn PM(10) only rarely exceed 50 ng/m(3), usually during desert dust intrusions which, in extreme cases (such as Canary Islands "calima" events from Africa) can produce Mn concentrations of 100 125 ng/m(3). PMID- 20582637 TI - Do patients seeking laparoscopic adjustable gastric banding surgery differ from those seeking gastric bypass surgery? A comparison of psychological profiles across ethnic groups. AB - BACKGROUND: Understanding presurgical psychological functioning is important in determining whether patients may benefit from psychological support before or after undergoing bariatric surgery. However, few studies have directly explored whether presurgical psychosocial profiles differ for patients presenting for different bariatric surgeries and what, if any, impact ethnic background might have. The present study compared presurgical depressive symptomatology, binge eating symptoms, and psychopathology in Caucasian and African American laparoscopic adjustable gastric banding (LAGB) and gastric bypass (RYGB) patients. METHODS: Patients (n=272) presenting for either LAGB or RYGB surgery completed self-report measures of depressive symptomatology (BDI), binge eating symptoms (BES), and psychopathology/personality (PAI) as part of the presurgical psychological evaluation. RESULTS: RYGB patients endorsed more depressive symptomatology, binge eating symptoms, somatic complaints, and antisocial features than LAGB patients, though higher BMI in the RYGB patients accounted for differences in binge eating symptoms. When the sample was examined by ethnic group, LAGB-RYGB differences were found only in African American, and not Caucasian, patients. CONCLUSIONS: Psychosocial profiles appear to differ for African American patients presenting for LAGB and RYGB surgeries; however, some of these differences are accounted for by differences in presurgical BMI. Gaining a better understanding of the initial psychological characteristics of bariatric surgery candidates may improve clinicians' abilities to identify and address specific areas of concern for these patients. PMID- 20582638 TI - Use of highly purified and mixed antibodies for simultaneous detection of multiple protein species released from mitochondria upon induction of the permeability transition. AB - Concomitant with the induction of the mitochondrial permeability transition (PT), cytochrome c is released from mitochondria into the cytosol where it triggers subsequent steps of cellular apoptosis. Thus, inducers of the mitochondrial PT would become "seed compounds" of regulators of apoptosis. However, when we examine the actions of certain chemicals on the release of mitochondrial cytochrome c, the behaviors of not only cytochrome c but also multiple mitochondrial protein species must be carefully examined because the mitochondrial PT and release of proteins from mitochondria occur in diverse manners. In the present study, we examined whether it is possible to measure the behaviors of multiple protein species in a single experiment using purified and mixed antibodies. The results obtained clearly indicate that this procedure would be applicable for high-throughput screening of regulators of apoptosis. Further requirements necessary for the establishment of a useful screening system for apoptosis regulators are discussed. PMID- 20582639 TI - Enzyme production by solid substrate fermentation of Pleurotus ostreatus and Trametes versicolor on tomato pomace. AB - A process of solid state fermentation (SSF) on tomato pomace was developed with the white-rot fungi Pleurotus ostreatus and Trametes versicolor, using sorghum stalks as support. Operative parameters (humidity, water activity, and size of substrate particles) guaranteeing a good colonization of tomato pomace by both fungi were defined and conditions for production at high titers of the industrially relevant enzymes laccase, xylanase and protease were identified. Significant laccase activity levels (up to 36 U g(-1) dry matter) were achieved without any optimization of culture conditions, neither by nutrient addition nor by O(2) enrichment. Furthermore, protease activity levels up to 34,000 U g(-1) dry matter were achieved, being higher than those reported for the fungi typically considered as the best protease producers such as Aspergillus strains. Moreover, as one of the most significant results of this study, analysis of P. ostreatus tomato SSF samples by zymogram revealed two bands with laccase activity which had not been detected so far. PMID- 20582640 TI - Production and characterization of cellobiohydrolase from a novel strain of Penicillium purpurogenum KJS506. AB - A high cellobiohydrolase (CBH)-producing strain was isolated and identified as Penicillium purpurogenum KJS506 according to the morphology and comparison of internal transcribed spacer rDNA gene sequence. When rice straw and corn steep powder were used as carbon and nitrogen sources, respectively, a maximum CBH activity of 2.6 U mg-protein(-1), one of the highest among CBH-producing microorganisms, was obtained. The optimum temperature and pH for CBH production were 30 degrees C and 4.0, respectively. The increased production of CBH in P. purpurogenum culture at 30 degrees C was confirmed by two-dimensional electrophoresis followed by MS/MS sequencing of the partial peptide. The internal amino acid sequences of P. purpurogenum CBH showed a significant homology with hydrolases from glycoside hydrolase family 7. The extracellular CBH was purified to homogeneity by sequential chromatography of P. purpurogenum culture supernatants on a DEAE-sepharose column, a gel filtration column, and then on a Mono Q column with fast-protein liquid chromatography. The purified CBH was a monomeric protein with a molecular weight of 60 kDa and showed broad substrate specificity with maximum activity towards p-nitrophenyl beta-D: cellobiopyranoside. P. purpurogenum CBH showed t (1/2) value of 4 h at 60 degrees C and V (max) value of 11.9 MUmol min(-1) mg-protein(-1) for p nitrophenyl-D: -cellobiopyranoside. Although CBHs have been reported, the high specific activity distinguishes P. purpurogenum CBH. PMID- 20582691 TI - Peroxyoxalate chemiluminescence detection for the highly sensitive determination of fluorescence-labeled chlorpheniramine with Suzuki coupling reaction. AB - A sensitive and selective high performance liquid chromatography-peroxyoxalate chemiluminescence (PO-CL) method has been developed for the simultaneous determination of chlorpheniramine (CPA) and monodesmethyl chlorpheniramine (MDCPA) in human serum. The method combines fluorescent labeling with 4-(4,5 diphenyl-1H-imidazole-2-yl)phenyl boronic acid using Suzuki coupling reaction with PO-CL detection. CPA and MDCPA were extracted from human serum by liquid liquid extraction with n-hexane. Excess labeling reagent, which interfered with trace level determination of analytes, was removed by solid-phase extraction using a C18 cartridge. Separation of derivatives of both analytes was achieved isocratically on a silica column with a mixture of acetonitrile and 60 mM imidazole-HNO(3) buffer (pH 7.2; 85:15, v/v) containing 0.015% triethylamine. The proposed method exhibited a good linearity with a correlation coefficient of 0.999 for CPA and MDCPA within the concentration range of 0.5-100 ng/mL. The limits of detection (S/N = 3) were 0.14 and 0.16 ng/mL for CPA and MDCPA, respectively. Using the proposed method, CPA could be selectively determined in human serum after oral administration. PMID- 20582641 TI - Heat treatment increases the incidence of alopecia areata in the C3H/HeJ mouse model. AB - Alopecia areata (AA) is a common autoimmune disease characterized by non-scarring hair loss. Previous studies have demonstrated an association between AA and physiological/psychological stress. In this study, we investigated the effects of heat treatment, a physiological stress, on AA development in C3H/HeJ mice. Whereas this strain of mice are predisposed to AA at low incidence by 18 months of age, we observed a significant increase in the incidence of hair loss in heat treated 8-month-old C3H/HeJ mice compared with sham-treated mice. Histological analysis detected mononuclear cell infiltration in anagen hair follicles, a characteristic of AA, in heat-treated mouse skin. As expected, increased expression of induced HSPA1A/B (formerly called HSP70i) was detected in skin samples from heat-treated mice. Importantly, increased HSPA1A/B expression was also detected in skin samples from C3H/HeJ mice that developed AA spontaneously. Our results suggest that induction of HSPA1A/B may precipitate the development of AA in C3H/HeJ mice. For future studies, the C3H/HeJ mice with heat treatment may prove a useful model to investigate stress response in AA. PMID- 20582692 TI - Integration of spore-based genetically engineered whole-cell sensing systems into portable centrifugal microfluidic platforms. AB - Bacterial whole-cell biosensing systems provide important information about the bioavailable amount of target analytes. They are characterized by high sensitivity and specificity/selectivity along with rapid response times and amenability to miniaturization as well as high-throughput analysis. Accordingly, they have been employed in various environmental and clinical applications. The use of spore-based sensing systems offers the unique advantage of long-term preservation of the sensing cells by taking advantage of the environmental resistance and ruggedness of bacterial spores. In this work, we have incorporated spore-based whole-cell sensing systems into centrifugal compact disk (CD) microfluidic platforms in order to develop a portable sensing system, which should enable the use of these hardy sensors for fast on-field analysis of compounds of interest. For that, we have employed two spore-based sensing systems for the detection of arsenite and zinc, respectively, and evaluated their analytical performance in the miniaturized microfluidic format. Furthermore, we have tested environmental and clinical samples on the CD microfluidic platforms using the spore-based sensors. Germination of spores and quantitative response to the analyte could be obtained in 2.5-3 h, depending on the sensing system, with detection limits of 1 x 10(-7) M for arsenite and 1 x 10(-6) M for zinc in both serum and fresh water samples. Incorporation of spore-based whole-cell biosensing systems on microfluidic platforms enabled the rapid and sensitive detection of the analytes and is expected to facilitate the on-site use of such sensing systems. PMID- 20582693 TI - Quantitation of plasmid DNA deposited on gold particles for particle-mediated epidermal delivery using ICP-MS. AB - DNA-plasmid-based vaccines are a promising class of next generation therapeutics. Particle-mediated epidermal delivery is an attractive method for the administration of DNA plasmid vaccines. This technology utilizes minute quantities of DNA plasmid which have been deposited onto the surface of 2-3 microm gold particles, and so the development of this technology requires the use of analytical methods that can accurately quantitate the amount of the DNA on the particle. Spectroscopic methods are generally insufficient for this task due to interference from the gold particle. ICP-MS circumvents this issue while allowing for the sensitive, reproducible, and accurate determination of the quantity of DNA on the particle surface. This report will detail the development and application of such a method. PMID- 20582694 TI - Spatially resolved determination of the structure and composition of diatom cell walls by Raman and FTIR imaging. AB - Vibrational spectroscopic imaging has developed into a versatile tool to study the local composition of various materials. Here, we present for the first time that Raman mapping and Fourier transform infrared imaging are useful tools to study diatom cell walls as is demonstrated for the species Stephanopyxis turris. The unicellular diatoms exhibit intricately micro- and nano-patterned cell walls, which consist of amorphous silica as well as various organic and inorganic constituents, thus making up an extremely interesting inorganic/organic hybrid material. The structure and composition of this material as well as the biochemical and biophysical processes leading to its formation remain to be challenges for ongoing research. Whereas the lateral resolution of Fourier transform infrared imaging is limited to 5 microm by diffraction, Raman maps are shown to be capable of detecting the spatial distribution of the silica as well as an additional inorganic component and the organic material down to 330-nm resolution. Due to the spherical shape of the sample with a radius of 40 microm and the requirement to accurately focus the laser before each Raman measurement within the micrometer range, Raman maps of whole diatom cell walls were registered after an adjustment of the axial position. The results reveal local differences in the cell wall composition of the honeycomb-like structures and the bottom layer. PMID- 20582695 TI - Comparison of CIM discs and CPG glass as solid supports for bioanalytical columns used in allergen detection. AB - This work presents a comparison of convective interaction media (CIM) and controlled pore glass (CPG) as solid supports for immunoglobulin antibodies used in bioanalytical detection of allergens in foodstuffs. A flow-injection manifold with highly sensitive thermal lens spectrometric detection was used for this purpose. Using beta-lactoglobulin, a milk allergen, as a model analyte, CIM disc supports had a higher linear range (0.2-3.5 microg L(-1)), better reproducibility (intra-day RSD = 1%, inter-day RSD = 10%), lower consumption of reagents, and better immunocolumn stability (1 month, over 240 injections of substrate), while providing comparable LODs (0.1 microg L(-1)). Application of CIM discs as solid supports in immunocolumns for allergen detection enables fast and sensitive screening of allergens in foodstuffs with sample throughput of up to eight samples per hour. PMID- 20582696 TI - A simple, sensitive and selective quantum-dot-based western blot method for the simultaneous detection of multiple targets from cell lysates. AB - Quantum dots (Qdots) are fluorescent nanoparticles that have great potential as detection agents in biological applications. Their optical properties, including photostability and narrow, symmetrical emission bands with large Stokes shifts, and the potential for multiplexing of many different colours, give them significant advantages over traditionally used fluorescent dyes. Here, we report the straightforward generation of stable, covalent quantum dot-protein A/G bioconjugates that will be able to bind to almost any IgG antibody, and therefore can be used in many applications. An additional advantage is that the requirement for a secondary antibody is removed, simplifying experimental design. To demonstrate their use, we show their application in multiplexed western blotting. The sensitivity of Qdot conjugates is found to be superior to fluorescent dyes, and comparable to, or potentially better than, enhanced chemiluminescence. We show a true biological validation using a four-colour multiplexed western blot against a complex cell lysate background, and have significantly improved previously reported non-specific binding of the Qdots to cellular proteins. PMID- 20582698 TI - Progress and possible applications of miniaturised separation techniques and elemental mass spectrometry for quantitative, heteroatom-tagged proteomics. AB - The application of miniaturised separation techniques such as capillary LC, nano LC or capillary electrophoresis offers a number of advantages in terms of analytical performance, solvent consumption and the ability to analyse very small sample amounts. These features make them attractive for various bioanalytical tasks, in particular those related to the analysis of proteins and peptides. The skillful combination of such techniques with inductively coupled plasma mass spectrometry (ICP-MS) has recently permitted the design of combined analytical approaches utilising either elemental or molecule-specific detection techniques such as electrospray ionisation (ESI) or matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry in a highly complementary manner for, as an example, proteomics-orientated research (heteroatom-tagged proteomics). Such hybrid approaches are, in particular, providing promising new options for the fast screening of complex samples for specific metal-containing or--more generally speaking--heteroatom-containing biomolecules, as well as the accurate absolute quantification of biomolecules, which is still an unsolved problem in bioanalysis. Here, progress in as well as the potential and the special requirements of hyphenating miniaturised separation techniques with ICP MS are reviewed and critically discussed. In addition, selected applications are highlighted to indicate current and possible future trends within this emerging area of research. PMID- 20582697 TI - Llama-derived single-domain antibodies for the detection of botulinum A neurotoxin. AB - Single-domain antibodies (sdAb) specific for botulinum neurotoxin serotype A (BoNT A) were selected from an immune llama phage display library derived from a llama that was immunized with BoNT A toxoid. The constructed phage library was panned using two methods: panning on plates coated with BoNT A toxoid (BoNT A Td) and BoNT A complex toxoid (BoNT Ac Td) and panning on microspheres coupled to BoNT A Td and BoNT A toxin (BoNT A Tx). Both panning methods selected for binders that had identical sequences, suggesting that panning on toxoided material may be as effective as panning on bead-immobilized toxin for isolating specific binders. All of the isolated binders tested were observed to recognize bead-immobilized BoNT A Tx in direct binding assays, and showed very little cross-reactivity towards other BoNT serotypes and unrelated protein. Sandwich assays that incorporated selected sdAb as capture and tracer elements demonstrated that all of the sdAb were able to recognize soluble ("live") BoNT A Tx and BoNT Ac Tx with virtually no cross-reactivity with other BoNT serotypes. The isolated sdAb did not exhibit the high degree of thermal stability often associated with these reagents; after the first heating cycle most of the binding activity was lost, but the portion of the protein that did refold and recover antigen-binding activity showed only minimal loss on subsequent heating and cooling cycles. The binding kinetics of selected binders, assessed by both an equilibrium fluid array assay as well as surface plasmon resonance (SPR) using toxoided material, gave dissociation constants (K(D)) in the range 2.2 x 10(-11) to 1.6 x 10(-10) M. These high-affinity binders may prove beneficial to the development of recombinant reagents for the rapid detection of BoNT A, particularly in field screening and monitoring applications. PMID- 20582699 TI - Exploratory analysis of human urine by LC-ESI-TOF MS after high intake of olive oil: understanding the metabolism of polyphenols. AB - Olive oil polyphenols have important biological properties which closely depend on their bioavailability; it is, therefore, essential to understand how polyphenols are absorbed, metabolized, and eliminated from the body. An analytical method based on rapid-resolution liquid chromatography (RRLC) coupled with mass spectrometric detection with a time-of-flight analyzer (RRLC-ESI-TOF MS) has been developed for analysis of the main olive oil phenolic compounds and their metabolites in human urine. Urine samples from ten healthy volunteers were collected before and 2, 4, and 6 h after intake of 50 mL extra-virgin olive oil. The proposed method includes liquid-liquid extraction with ethyl acetate, which provides extraction recoveries of the phenolic compounds studied between 35 and 75% from spiked urine samples. Good repeatability was obtained--the relative standard deviations (RSDs) of peak areas in intra-day and inter-day studies were 4.3 and 6.5%, respectively. Statistical studies enabled us to discriminate between urine samples before and after intake, and facilitated the search for m/z values enabling this discrimination. Based on the very accurate mass information and the isotopic pattern provided by the TOF MS analyzer, together with other available information, ten of these biomarkers and more than 50 metabolites, obtained through phase I and phase II biotransformation reactions, were tentatively identified. Additionally, kinetic studies were conducted on the metabolites identified as possible biomarkers; for most of the compounds concentrations were maximum in the first two hours. PMID- 20582700 TI - Right paraduodenal hernia: characteristic MDCT findings. AB - Right paraduodenal hernia is a very rare cause of abdominal pain. It can lead to bowel obstruction, ischemia, and perforation with a high mortality. A timely and correct diagnosis with a rapid diagnostic tool is mandatory. However, clinical diagnosis of right paraduodenal hernia is difficult for its nonspecific symptoms. Traditionally, paraduodenal hernia was diagnosed by small bowel series that was a time-consuming image study. We report a case of right paraduodenal hernia with pre-operative fast diagnosis by multidetector row computed tomography. Fortunately, the ischemic bowel loops were timely alleviated by reduction and resection was prevented. PMID- 20582701 TI - Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours. AB - OBJECTIVE: Percutaneous biopsies are gaining acceptance in the diagnosis of soft tissue tumours. Sampling in the most representative area is not easy in sarcomas of huge dimension. We hypothesised that ultrasound (US) contrast medium could identify the representative area for focus core-needle biopsy (CNB) METHODS: This is a retrospective cohort series of 115 soft-tissue masses treated from January 2007 to November 2008. Accuracy of US-guided CNB after contrast-enhanced US (CEUS) was determined by comparing the histology of the biopsy with the definitive diagnosis in 105 surgically excised samples (42 benign, 63 malignant) and with the expected outcome in the remaining ten malignant cases not surgically treated. A myxoid component was present in 21 sarcomas (34.4%). RESULTS: Of samples, 94.8% were adequate for diagnosis with 97.1% sensitivity and 92.5% specificity. Sensitivity and specificity in specific histopathological subgroupings were 100%, and in grading definition they were 100% and 96.8%. DISCUSSION: US-guided CNB is safe and effective. US contrast medium depicts tumour vascular supply and identifies the representative area(s) for sampling. Sensitivity and specificity are also high in subgrouping and grading, including myxoid types. Discussion about biopsy is part of the essential multidisciplinary strategy for these tumours. PMID- 20582702 TI - Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis. AB - BACKGROUND: Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high risk women. METHODS: A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). RESULTS: Of 127 articles found, 7 were selected for the meta analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of >=5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. CONCLUSION: Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. PMID- 20582703 TI - Dissociation between cVEMP and oVEMP responses: different vestibular origins of each VEMP? PMID- 20582704 TI - Fear of recurrence following head and neck cancer in the outpatient clinic. AB - Fear of recurrence (FOR) following head and neck cancer is one of the most frequent concerns of patients and is associated with psychological distress. The aims of this study were, first, to report the clinical characteristics of patients selected for FOR concerns on a patient concerns inventory (PCI) and, second, to compare the degree of FOR using a FOR questionnaire of those patients expressing FOR concerns on the PCI with those who did not. Two cohorts were used. The first comprised consecutive oncology patients attending clinics from August 2007 for 9 months (N = 123). These patients completed the PCI only. The second comprised patients attending the same clinic for over 4 months from October 2008 (N = 68), and this group completed both the PCI and the FOR questionnaire. FOR was the most frequently selected issue on the PCI (42%). There were no obvious differences in selecting FOR by patient characteristics. Those who scored 'a lot' or 'all the time' for questions 1-6 in the FOR questionnaire and responses (on a 10-point scale) of 7-10 for question 7 were deemed as having 'significant' FOR. In those raising the issue of FOR on the PCI, 79% (15/19) had significant problems compared to 24% (12/49) if they did not. FOR is a common concern and because it is not possible to identify patients based on clinical parameters, it is important to screen for FOR to direct patients to appropriate support and intervention. PMID- 20582706 TI - Intravitreal bevacizumab in combination with laser therapy for the treatment of severe retinopathy of prematurity (ROP) associated with vitreous or retinal hemorrhage. AB - PURPOSE: To evaluate outcomes of intravitreal injection of bevacizumab for the treatment of severe retinopathy of prematurity (ROP) associated with vitreous or retinal hemorrhages (VH or RH). METHODS: This is a prospective interventional case-series. Fourteen eyes of eight premature infants with severe ROP associated with vitreous or retinal hemorrhage were consecutively included. In eight eyes, VH and/or RH precluding complete laser ablation developed at the time of laser treatment. In six eyes, VH developed early after laser ablation. All participants underwent intravitreal injection of 0.625 mg (0.025 ml) bevacizumab immediately after diagnosis of VH or RH. Follow-up examinations were performed at days 1, 3, 7, and 14, and 1, 2 and 3 months after injection. Main outcome measure was the absence of unfavorable structural outcomes. RESULTS: Mean gestational age was 27.6 weeks (range, 26-29 weeks) and mean birth weight was 1047 g (range, 780-1500 g). Mean gestational age at the time of injection was 35.4 weeks (range, 32-38 weeks). In all eyes, plus disease disappeared completely within 2 weeks and VH and/or RH was absorbed at last follow-up. None of the eyes developed unfavorable structural outcomes. No eyes needed additional injection or laser treatment. No major systemic or ocular complications were observed. CONCLUSION: In this small series of patients, intravitreal injection of bevacizumab was effective for treatment of severe retinopathy of prematurity associated with vitreous or retinal hemorrhage. PMID- 20582705 TI - Ultrastructural changes of cornea after ethanol ingestion in Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats. AB - PURPOSE: To compare ethanol-induced ultrastructural changes in corneas of Otsuka Long-Evans Tokushima fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats. METHODS: Forty, five-week-old male LETO and OLETF rats were fed an ethanol containing liquid diet (LETO alc and OLETF alc) for 11 weeks, and another forty OLETF and LETO rats were put on a pair-fed control diet (LETO con and OLETF con) for 11 weeks. The body weight and fasting blood glucose levels, and 2-hour blood glucose levels after glucose tolerance test (GTT) were checked every week. Central corneal thickness (CCT) was measured with an ultrasound pachymeter after 11 weeks. After corneal buttons were excised, transmission electron microscopy (TEM) examination was performed. RESULTS: The CCTs in groups LETO-alc (179.39 +/- 28.64 microm) and OLETF-alc (189.46 +/- 44.44 microm) were significantly thicker than those in groups LETO-con (168.07 +/- 15.57 microm) and OLETF-con (179.28 +/- 14.68 microm) respectively (P < 0.05). The percentage of basement membrane occupied by hemidesmosome (HD/BM) in the LETO-alc (43.2 +/- 3.7%) and OLETF-alc (35.3 +/- 4.1%) was lower than that in the LETO-con (51.5 +/- 2.6%) and OLETF-con (41.6 +/- 3.5%) group respectively (P < 0.05). Descemet's membrane thickness of the LETO-alc (4.45 +/- 0.3 microm) and OLETF-alc (4.98 +/- 0.5 microm) was greater than that of the LETO-con (4.11 +/- 0.2 microm) and OLETF-con (4.57 +/- 0.3 microm) group respectively (P < 0.05). In the OLETF group, the hemidesmosomes and endothelial tight junctions were less electron-dense; interstromal edema was more prominent than that in the LETO group. CONCLUSIONS: Corneal ultrastructural damage can develop in the pre-diabetic stage and when alcohol is ingested chronically in rats. PMID- 20582707 TI - Equilibrium of vegetation and climate at the European rear edge. A reference for climate change planning in mountainous Mediterranean regions. AB - Mediterranean mountains harbour some of Europe's highest floristic richness. This is accounted for largely by the mesoclimatic variety in these areas, along with the co-occurrence of a small area of Eurosiberian, Boreal and Mediterranean species, and those of Tertiary Subtropical origin. Throughout the twenty-first century, we are likely to witness a climate change-related modification of the biogeographic scenario in these mountains, and there is therefore a need for accurate climate regionalisations to serve as a reference of the abundance and distribution of species and communities, particularly those of a relictic nature. This paper presents an objective mapping method focussing on climate regions in a mountain range. The procedure was tested in the Cordillera Central Mountains of the Iberian Peninsula, in the western Mediterranean, one of the ranges occupying the largest area of the Mediterranean Basin. This regionalisation is based upon multivariate analyses and upon detailed cartography employing 27 climatic variables. We used spatial interpolation of data based on geographic information. We detected high climatic diversity in the mountain range studied. We identified 13 climatic regions, all of which form a varying mosaic throughout the annual temperature and rainfall cycle. This heterogeneity results from two geographically opposed gradients. The first one is the Mediterranean-Euro Siberian variation of the mountain range. The second gradient involves the degree of oceanicity, which is negatively related to distance from the Atlantic Ocean. The existing correlation between the climatic regions detected and the flora existing therein enables the results to be situated within the projected trends of global warming, and their biogeographic and ecological consequences to be analysed. PMID- 20582708 TI - Risk analysis of blood transfusion requirements in emergency and elective spinal surgery. AB - Spinal surgery has long been considered to have an elevated risk of perioperative blood loss with significant associated blood transfusion requirements. However, a great variability exists in the blood loss and transfusion requirements of differing patients and differing procedures in the area of spinal surgery. We performed a retrospective study of all patients undergoing spinal surgery who required a transfusion>=1 U of red blood cells (RBC) at the National Spinal Injuries Unit (NSIU) at the Mater Misericordiae University Hospital over a 10 year period. The purpose of this study was to identify risk factors associated with significant perioperative transfusion allowing the early recognition of patients at greatest risk, and to improve existing transfusion practices allowing safer, more appropriate blood product allocation. 1,596 surgical procedures were performed at the NSIU over a 10-year period. 25.9% (414/1,596) of these cases required a blood transfusion (n=414). Surgical groups with a significant risk of requiring a transfusion>2 U RBC included deformity surgery (RR=3.351, 95% CI 1.123-10.006, p=0.03), tumor surgery (RR=3.298, 95% CI 1.078-10.089, p=0.036), and trauma surgery (RR=2.444, 95% CI 1.183-5.050, p=0.036). Multivariable logistic regression analysis identified multilevel surgery (>3 levels) as a significant risk of requiring a transfusion>2 U RBC (RR=4.682, 95% CI 2.654 8.261, p<0.0001). Several risk factors in the spinal surgery patient were identified as corresponding to significant transfusion requirements. A greater awareness of the risk factors associated with transfusion is required in order to optimize patient management. PMID- 20582709 TI - Anterior shear strength of the porcine lumbar spine after laminectomy and partial facetectomy. AB - Degenerative lumbar spinal stenosis is the most common reason for lumbar surgery in patients in the age of 65 years and older. The standard surgical management is decompression of the spinal canal by laminectomy and partial facetectomy. The effect of this procedure on the shear strength of the spine has not yet been investigated in vitro. In the present study we determined the ultimate shear force to failure, the displacement and the shear stiffness after performing a laminectomy and a partial facetectomy. Eight lumbar spines of domestic pigs (7 months old) were sectioned to obtain eight L2-L3 and eight L4-L5 motion segments. All segments were loaded with a compression force of 1,600 N. In half of the 16 motion segments a laminectomy and a 50% partial facetectomy were applied. The median ultimate shear force to failure with laminectomy and partial facetectomy was 1,645 N (range 1,066-1,985) which was significantly smaller (p = 0.012) than the ultimate shear force to failure of the control segments (median 2,113, range 1,338-2,659). The median shear stiffness was 197.4 N/mm (range 119.2-216.7) with laminectomy and partial facetectomy which was significantly (p = 0.036) smaller than the stiffness of the control specimens (median 216.5, 188.1-250.2). It was concluded that laminectomy and partial facetectomy resulted in 22% reduction in ultimate shear force to failure and 9% reduction in shear stiffness. Although relatively small, these effects may explain why patients have an increased risk of sustaining shear force related vertebral fractures after spinal decompression surgery. PMID- 20582710 TI - Anterior versus posterior surgery for multilevel cervical myelopathy, which one is better? A systematic review. AB - The objective of the study is to perform a systematic review to compare the clinical outcomes and complications of anterior surgery with posterior surgery for multilevel cervical myelopathy (MCM). MEDLINE, EMBASE databases and other databases were searched for all the relevant original articles published from January 1991 to November 2009 comparing anterior with posterior surgery for MCM. Subgroup analysis was performed according to the follow-up years. The following end points were mainly evaluated: final follow-up JOA (Japanese Orthopaedic Association) scale, recovery rate and complication outcomes. Ten articles fulfilled all inclusion criteria. For multilevel CSM patients, the final follow up JOA score for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 0.83 [0.24, 1.43]) in the 'follow-up time <= 5 years' subgroup, but had no significant differences in the 'follow-up time > 5 years' subgroup (p > 0.05). The recovery rate for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 10.08 [1.39, 18.78]) in the 'follow-up time <= 5 years' subgroup. No study reported the recovery rate for the follow-up time > 5 years. For multilevel OPLL patients, the final follow-up JOA score and recovery rate for the anterior group were both significantly higher than the posterior group in the 'follow-up time <= 5 years' subgroup (p < 0.05, WMD 2.50 [0.16, 4.85]; p < 0.05, WMD 29.48 [29.09, 29.87], respectively). One study [31] which mean follow-up time was 6 years was enrolled in the 'follow-up time > 5 years' subgroup. The results showed there was no significant difference in final follow-up JOA score and recovery rate between anterior and posterior group for patients with occupying ratio of OPLL <60% (p > 0.05), while in patients with occupying ratio >= 60%, the final follow-up JOA score and recovery rate of anterior surgery were both superior to that of posterior surgery (p < 0.05). For both multilevel CSM and OPLL patients, the complications for the anterior group were significantly more than the posterior group in the 'follow-up time <= 5 years' subgroup (p < 0.05, OR 7.33 [2.96, 18.20] for CSM patients; p < 0.05, OR 4.44 [1.80, 10.98] for OPLL patients), but were similar to the posterior group in the 'follow-up time >5 years' subgroup (p > 0.05). In conclusion, anterior surgery had better clinical outcomes and more complications at the early stage after operation for both multilevel CSM and OPLL patients. At the late stage, posterior surgery had similar clinical outcomes and complications to anterior surgery for CSM patients, and OPLL patients with occupying ratio of OPLL <60%. While for OPLL patients with occupying ratio >= 60%, anterior surgery had superior clinical outcome to posterior surgery. PMID- 20582711 TI - Cytoplasmic membrane fluidity and fatty acid composition of Acidithiobacillus ferrooxidans in response to pH stress. AB - Strain variation in the acidophile Acidithiobacillus ferrooxidans was examined as a product of membrane adaptation in response to pH stress. We tested the effects of sub and supra-optimal pH in two type strains and four strains isolated from acid mine drainage water around Sudbury, Ontario, Canada. Growth rate, membrane fluidity and phase, determined from the fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene, and fatty acid profiles were compared. The effect of pH 1.5 was the most pronounced compared to the other pH values of 1.8, 3.1, and 3.5. Three different types of response to lower pH were observed, the first of which appeared to maintain cellular homeostasis more effectively. This adaptive mode included a decrease in membrane fluidity and concomitant depression of the phase transition in two distinct membrane lipid components. This was explained through the increase in saturated fatty acids (predominantly 16:0 and cyclopropane 19:0 w8c) with a concomitant decrease in 18:1 w7c fatty acid. The other strains also showed common adaptive mechanisms of specific fatty acid remodeling increasing the abundance of short-chain fatty acids. However, we suspect membrane permeability was compromised due to potential phase separation, which may interfere with energy transduction and viability at pH 1.5. We demonstrate that membrane physiology permits differentiating pH tolerance in strains of this extreme acidophile. PMID- 20582713 TI - Honokiol: an effective inhibitor of high-glucose-induced upregulation of inflammatory cytokine production in human renal mesangial cells. AB - OBJECTIVE: To evaluate the regulatory effects of honokiol on high-glucose (HG) induced inflammatory responses of human renal mesangial cells (HRMCs). MATERIALS AND METHODS: We performed MTS assays to determine the non-cytotoxic concentration of honokiol for HRMCs. Enzyme-linked immunosorbent assays were performed to analyze the expressions of the proteins interleukin (IL)-1beta, IL-18, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, RANTES, and prostaglandin (PG) E2. The total nitric oxide (NO) concentration was determined using the Griess reaction. RESULTS: Treatment with 50 mmol/L glucose markedly increased the level of IL-1beta, IL-18, TNF-alpha, PGE2, NO, TGF-beta1, MCP-1, MIP-1alpha, and RANTES. Honokiol (~20 MUmol/L) treatment inhibited the HG induced expression of inflammatory cytokines such as IL-1beta, IL-18, TNF-alpha, PGE2, NO, and TGF-beta1 in a dose-dependent manner. Moreover, it markedly inhibited the expression of chemokines such as MCP-1, MIP-1alpha, and RANTES, which are upregulated under HG conditions. CONCLUSION: Honokiol inhibits the HG induced expression of inflammatory factors in HRMCs. Honokiol may be considered a promising drug with potent anti-inflammatory activities in addition to its strong anti-cancer, anti-angiogenesis, and anti-neurodegenerative effects. PMID- 20582712 TI - Functional genomics of soybean for improvement of productivity in adverse conditions. AB - Global soybean production is frequently impacted by various stresses, including both abiotic and biotic stresses. To develop soybean plants with enhanced tolerance to different stressors, functional genomics of soybean and a comprehensive understanding of available biotechnological resources and approaches are essential. In this review, we will discuss recent advances in soybean functional genomics which provide unprecedented opportunities to understand global patterns of gene expression, gene regulatory networks, various physiological, biochemical, and metabolic pathways as well as their association with the development of specific phenotypes. Soybean functional genomics, therefore, will ultimately enable us to develop new soybean varieties with improved productivity under adverse conditions by genetic engineering. PMID- 20582715 TI - Functional analysis of SlEZ1 a tomato enhancer of zeste (E(z)) gene demonstrates a role in flower development. AB - The Enhancer of Zeste (E(z)) Polycomb group (PcG) proteins, which are encoded by a small gene family in Arabidopsis thaliana, have been shown to participate to the control of flowering and seed development. For the time being, little is known about the function of these proteins in other plants. In tomato E(z) proteins are encoded by at least two genes namely SlEZ1 and SlEZ2 while a third gene, SlEZ3, is likely to encode a truncated non-functional protein. The analysis of the corresponding mRNA demonstrates that these two genes are differentially regulated during plant and fruit development. We also show that SlEZ1 and SlEZ2 are targeted to the nuclei. These results together with protein sequence analysis makes it likely that both proteins are functional E(z) proteins. The characterisation of SlEZ1 RNAi lines suggests that although there might be some functional redundancy between SlEZ1 and SlEZ2 in most plant organs, the former protein is likely to play specific function in flower development. PMID- 20582714 TI - Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes. AB - OBJECTIVE AND DESIGN: Monocyte locomotion inhibitory factor (MLIF), an amebic peptide with antiinflammatory properties, was evaluated in collagen-induced arthritis (CIA) to test its effects on the onset and acute inflammatory response of arthritis. MATERIAL: DBA1/J mice at 8-10 weeks of age were divided into four groups (eight mice per group). TREATMENT: The adjuvant group received Freund adjuvant, the CIA group was immunized with collagen II, the MLIF/CIA group received collagen II and MLIF, and the MLIF group received MLIF and Freund adjuvant. METHODS: All groups were evaluated clinically. Seven weeks after the collagen injection, at the peak of the clinical arthritis score, limb specimens were collected and histological studies and gene expression analysis using microarrays were performed. RESULTS: MLIF administered weekly as a preventive scheme delayed and reduced the severity of acute arthritis. MLIF induced gene changes in functional categories including adhesion molecules, matrix metalloproteinases, and inflammatory cytokines. CONCLUSIONS: MLIF could be an interesting new molecule to investigate in the field of rheumatoid arthritis pathogenesis research for its potential to prevent inflammation. PMID- 20582716 TI - Bone-like nanocomposites based on self-assembled protein-based matrices with Ca2+ capturing capability. AB - In the present work, bone-like nanocomposites have been successfully synthesized based on the mineralization of self-assembled protein-based microgels. Such mircogels were achieved by the in vitro reconstitution of collagen monomeric solutions in the presence of alginate in a microemulsion system. Microstructural observations revealed that the collagen-alginate composite beads possessed a nanofibrous three dimensional (3D) interconnected porous microstructure. The obtained microgels were pre-incubated in calcium-containing solution to capture Ca(2+) ions, and subsequently immersed in phosphate-containing solution to initiate the formation of hydroxyapatite (HA) by an alternative incubating procedure. It was observed that a substantial amount of bone-like apatite nanocrystals were orderly and homogeneously deposited throughout the porous fibrillar networks. Herein, the collagen-alginate composite microgels served as a mineralization template for the synthesis of HA-polymer nanocomposites, which could be ideal vehicles potentially for cell carriers, bone repair and proteins and drugs delivery in tissue regeneration. PMID- 20582717 TI - Physical activity levels after treatment for breast cancer: one-year follow-up. AB - Among patients with breast cancer, few studies have examined the pattern of change of physical activity levels over time or the predictive factors for this change. Particularly sparse are studies comparing pre-surgical physical activity levels with those 12 months post-surgery. Patients with a primary operable breast cancer (N = 267) filled in the Physical Activity Computerised Questionnaire before breast surgery and 1, 3, 6 and 12 months post-operatively. Patient-, disease- and treatment-related factors were prospectively collected. Total physical activity level and occupational, sport and household activity levels were significantly decreased the first month post-operatively and did not recover during the first year after surgery. 'Being employed' was a predictive factor for a larger decrease of the total activity level, comparing the pre-operative and 12 months post-surgery stages. Having a spouse, a pN2-3 lesion and over 20 lymph nodes dissected predicted a decrease in occupational activity. Advanced age and smoking behaviour predicted a decrease in sport activities, and not having a spouse predicted a decrease in household activities. This study showed that 1 year after breast cancer surgery, pre-operative physical activity levels were not recovered. Breast cancer patients, and in particular those at risk for a decreased physical activity level, should be identified, encouraged and guided to increase their activities. PMID- 20582718 TI - Ketosis in buffalo (Bubalus bubalis): clinical findings and the associated oxidative stress level. AB - As little is known about the oxidant/antioxidant status in buffalo with ketosis, the present study was delineated to assess the oxidative stress level associated with clinical ketosis in water buffalo. A total of 91 parturient buffalo at smallholder farms were studied (61 suspected to be ketotic and 30 healthy). Clinical and biochemical investigations were carried out for each buffalo. Based on clinical findings and the level of beta-hydroxybutyrate (BHB), buffalo were allocated into ketotic (42), subclinical cases (19). Clinically, there was an association between clinical ketosis and anorexia (p<0.001), constipation (p<0.001), decreased milk yield (p<0.001), ruminal stasis (p<0.001), and loss of body condition (p<0.01). Biochemically, in clinical ketosis compared with subclinical and control cases, there was a significant increase (p<0.05) of BHB, malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase (AST), L alanine aminotransferase (ALT). However, there was a significant decrease of glucose, phosphorus, magnesium,total cholesterol and HDL-cholesterol. There was a positive correlation between BHB and MDA (r=0.433), BHB and NO (r=0.37), MDA and NO (r=0.515), and Glucose and phosphorus(r=0.521). However, there was a negative correlation between BHB and glucose (r= -0.341) and HDL and NO (r= -0.379). The result of the present study indicates that hyperketonemia in buffalo is associated with an increase of oxidative stress levels. Further studies need to be done on the efficacy of antioxidants as an ancillary treatment to relief the oxidative stress caused by ketosis. PMID- 20582719 TI - Investigation of African swine fever in slaughtered pigs, Plateau state, Nigeria, 2004-2006. AB - The occurrence of African swine fever (ASF) DNA in slaughtered pigs in the major pig producing areas of Plateau state over a 2-year period was investigated. Three hundred fifty-nine pig tissue samples from five local government councils (LGCs) were analyzed by clinical signs (C/S), postmortem (PM) lesions and polymerase chain reaction (PCR). The results of diagnosis made by C/S and PM were compared to results obtained by PCR. Out of the 359 abattoir samples, 13 (3.62%) were positive by examination of C/S and PM lesions while 346 (96.38%) were negative. Jos-north LGC had the highest occurrence of PCR positive samples (31 samples); Panyam in Mangu LGC had no positive result. PCR analysis identified 53 positive samples (14.76%); more than 40 were identified on the field. Of the samples, 306 were PCR negative, thus giving a true ASF status of pigs in Plateau state. Analysis of the results, variables involved in the ASF spread and predictable effects of such findings in the pig industry in Plateau state and Nigeria as a whole is discussed. PMID- 20582720 TI - Factorial invariance, scale reliability, and construct validity of the job control and job demands scales for immigrant workers: the multi-ethnic study of atherosclerosis. AB - Immigrants have a different social context from those who stay in their home country or those who were born to the country that immigrants now live. Cultural theory of risk perception suggests that social context influences one's interpretation of questionnaire items. We examined psychometric properties of job control and job demand scales with US- and foreign-born workers who preferred English, Spanish, or Chinese (n = 3,114, mean age = 58.1). Across all groups, the job control scale had acceptable Cronbach's alpha (0.78-0.83) and equivalent factor loadings (DeltaCFI < 0.01). Immigrants had low alpha (0.42-0.65) for the job demands scale regardless of language, education, or age of migration. Two job demand items had different factor loadings across groups. Among immigrants, both scales had inconsistent associations with perceived job stress and self-rated health. For a better understanding of immigrants' job stress, the concept of job demands should be expanded and immigrants' expectations for job control explored. PMID- 20582721 TI - Health- and oral health-related quality of life among preschool children with cerebral palsy. AB - OBJECTIVES: To assess the health- and oral health-related quality of life of preschool children with cerebral palsy (CP) and to determine their inter relationship between the two quality of life measures. METHODS: A total of 144 preschool children with and without CP were invited to participate in the case control study. Health-related quality of life was assessed by the Pediatric Quality of Life Inventory Version 4.0 (PedsQLTM 4.0) and oral health-related quality of life by the Early Childhood Oral Health Impact Scale (ECOHIS). Differences in PedsQLTM 4.0 and ECOHIS scores were determined between the groups, and correlation between PedsQL and ECOHIS were explored. RESULTS: Significant differences in overall scores of PedsQLTM 4.0 (P < 0.001) and in overall scores of ECOHIS (P < 0.05) were apparent between the two groups. In terms of health- and oral health-related quality of life, preschool children with CP fared worse than the age-gender-matched control group. There was a positive albeit weak correlation (r = 0.203, P < 0.05) between PedsQLTM 4.0 and ECOHIS scores. CONCLUSIONS: Differences in health- and oral health-related quality of life exist among preschool children with CP. Correlation between health- and oral health related quality of life could at best be described as weak. PMID- 20582722 TI - Measuring community integration after spinal cord injury: validation of the Sydney psychosocial reintegration scale and community integration measure. AB - OBJECTIVES: To evaluate the reliability, validity, sensitivity to change, and clinical usefulness of the Sydney Psychosocial Reintegration Scale (SPRS) and Community Integration Measure (CIM) for people with spinal cord injury (SCI). METHODS: A sample of 58 people with recent traumatic SCI was followed up at 12 months post-discharge from inpatient rehabilitation. The SPRS, CIM, Craig Handicap Assessment and Reporting Technique (CHART) and SF-6D Health Utility Scale (SF-6D) were administered. RESULTS: The SPRS and CIM were internally consistent (alpha = .80 and .78, respectively). The SPRS showed greatest sensitivity to change as measured by percentage of participants meeting minimum difference in score change over time (21%). CIM and CHART had comparable sensitivity to change (14% minimum difference). SPRS correlated significantly with CHART (r = .72, P < .001), unlike CIM. Neither SPRS nor CIM discriminated between high and low impairment, unlike CHART. Correlations with CHART and SF-6D domains supported convergent and divergent validity of the SPRS domains. CONCLUSIONS: Research should continue to develop conceptually and psychometrically valid instruments to capture the multidimensionality of community integration. The SPRS and CIM show potential to extend measurement of community reintegration following SCI. PMID- 20582723 TI - Methods of emulsifying linoleic acid in biohydrogenation studies in vitro may bias the resulting fatty acid profiles. AB - The effects of three emulsifying methods on ruminal fatty acid biohydrogenation (BH) in vitro were compared. Using a static in-vitro gas test system, four replicates of each treatment were incubated in buffered ruminal fluid. Hemicellulose (300 mg dry matter) was supplemented either with or without linoleic acid (9c12c-18:2, 5% in diet dry matter) and incubated for 4 and 24 h. Three methods of emulsifying 9c12c-18:2 were tested: (1) ethanol, (2) Tween 80, and (3) sonication. The products were then compared to non-emulsified 9c12c-18:2. Out of the three emulsifying methods tested, ethanol and sonication resulted in stable 9c12c-18:2 emulsions, indicating good 9c12c-18:2 distribution, while the Tween 80 emulsion was less stable. BH was strongly inhibited by treating 9c12c 18:2 with ethanol and sonication at different steps of the BH-pathway, resulting in changed concentrations of certain BH intermediates. The fatty acid profile generated from the major BH-pathways of 9c12c-18:2 with Tween 80 was comparable to that without emulsification after 24 h of incubation. We conclude that it is not recommended to emulsify lipids before incubating them in vitro when investigating fatty acid BH. If emulsification of 9c12c-18:2 is necessary, Tween 80 seems to be the method that interferes least with BH. PMID- 20582726 TI - Delayed-onset PTSD among war veterans: the role of life events throughout the life cycle. AB - BACKGROUND: The underlying mechanisms of delayed-onset PTSD are yet to be understood. This study examines the role of stressful life events throughout the life cycle in delayed-onset PTSD following combat. METHODS: 675 Israeli veterans from the 1982 Lebanon War, 369 with antecedent combat stress reaction (CSR) and 306 without CSR were assessed prospectively, 1, 2 and 20 years after the war. Veterans were divided into four groups, according to the time of first PTSD onset (first onset at 1983, 1984, and 2002 and no PTSD onset). They were assessed for post-, peri- and pre-traumatic life events, as well as military and socio demographic characteristics. RESULTS: Our findings indicate that shorter delays in PTSD onset were associated with a higher risk for CSR, a higher number of pre- and post-war life events, more severe subjective battle exposure, greater perceived danger during combat and a more stressful military position. CSR was found to be the most powerful predictor of PTSD onset. A recency effect was also found, with more recent life events proving to be stronger predictors of PTSD onset. CONCLUSIONS: First, our findings validate the existence of delayed-onset PTSD, as it was found among a substantial number of participants (16.5%). Second, post-, peri- and pre-traumatic life events are associated with the time of PTSD onset. Thus, practitioners and researchers are encouraged to examine not only the original trauma, but also the stressful experiences throughout the survivors' life cycle. In particular, identification of antecedent CSR may help mental help professionals in targeting high-risk populations. PMID- 20582727 TI - Endosymbiosis of Chlorella species to the ciliate Paramecium bursaria alters the distribution of the host's trichocysts beneath the host cell cortex. AB - Each symbiotic Chlorella of the ciliate Paramecium bursaria is enclosed in a perialgal vacuole membrane derived from the host digestive vacuole membrane. Alga free paramecia and symbiotic algae can grow independently. Mixing them experimentally can cause reinfection. Earlier, we reported that the symbiotic algae appear to push the host trichocysts aside to become fixed beneath the host cell cortex during the algal reinfection process. Indirect immunofluorescence microscopy with a monoclonal antibody against the trichocysts demonstrates that the trichocysts change their locality to form algal attachment sites and decrease their density beneath the host cell cortex through algal reinfection. Transmission electron microscopy to detect acid phosphatase activity showed that some trichocysts near the host cell cortex are digested by the host lysosomal fusion during algal reinfection. Removal of algae from the host cell using cycloheximide recovers the trichocyst's arrangement and number near the host cell cortex. These results indicate that symbiotic algae compete for their attachment sites with preexisting trichocysts and that the algae have the ability to ensure algal attachment sites beneath the host cell cortex. PMID- 20582728 TI - B-lymphocyte activating factor levels are increased in patients with Wegener's granulomatosis and inversely correlated with ANCA titer. AB - Circulating autoantibodies against neutrophils (ANCA) are a distinctive finding in patients with Wegener's granulomatosis (WG). B-lymphocyte activating factor (BAFF) promotes autoantibody production by increasing B cell survival and proliferation. We investigated serum BAFF levels (s-BAFF) in a WG patient cohort in relation to ANCA titers and disease activity. Baseline data were obtained in twenty-two WG patients (55% female, age 44 years, disease duration 1 year). S BAFF was determined by capture ELISA and associations between s-BAFF, clinical (Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI) and Disease Extent Index (DEI)) and biochemical (C-reactive protein (CRP), IgG and ANCA) disease measures were analysed in a cross sectional as well as longitudinal analysis. S-BAFF was increased in WG patients compared to healthy controls (1.8 vs. 0.55 ng/ml, p < 0.01). S-BAFF was higher in ANCA negative than ANCA-positive WG sera (2.16 vs. 1.29 ng/ml, p < 0.01), correlated independently and inversely with ANCA levels (Rs -0.48, p < 0.01) but did not correlate with CRP, BVAS, DEI or VDI scores. Individual s-BAFF profiles were stable over time in 68% of patients. The finding of a negative correlation between ANCA levels and s-BAFF that is independent of steroid treatment indicates that BAFF does not directly drive ANCA production in WG. PMID- 20582729 TI - Cyclical changes in collagen concentration in relation to growth and development of buffalo corpus luteum. AB - In the present study, changes in luteal fresh weight and concentration of collagen in cyclic buffalo corpus luteum were investigated at 4 stages of its growth and development/regression. The collagen concentration was determined by estimating hydroxyproline, a collagen specific amino acid present in luteal tissues. The mean fresh weight increased (P < 0.001) over the luteal phase, reached maximum at late-luteal stage and decreased (P < 0.001) subsequently at follicular stage. The weight of the mature CL was 2.5 times heavier than the CL haemorrhagicum and regressing CL. Results showed that cyclic buffalo CL contains collagen at all 4 stages of development during oestrous cycle. The collagen in luteal tissues constitutes about 0.9% to 1.2% of luteal fresh weight with the highest content appearing in mature tissue. The concentration of collagen increased (P < 0.001) with the stages of CL development over the luteal phase and the highest concentration was recorded at follicular phase with the decline of luteal weight. The total content of collagen per CL also showed the same trend during luteal phase but decreased at follicular phase with the loss of luteal tissues. In conclusion, collagen concentration in cyclic buffalo CL changes with the growth and development of CL across the oestrous cycle. The synthesis of collagen is faster between early- to mid-luteal stage than mid- to late-luteal stage. PMID- 20582730 TI - Personal identity and bioethics: the state of the art. AB - In this introduction to the special issue of Theoretical Medicine and Bioethics on the topic of personal identity and bioethics, I provide a background for the topic and then discuss the contributions in the special issue by Eric Olson, Marya Schechtman, Tim Campbell and Jeff McMahan, James Delaney and David Hershenov, and David DeGrazia. PMID- 20582731 TI - Variations in short tandem repeats deduced on the basis of the number of repeats and the relationship of these variations with longevity. AB - The objective of this study was to investigate the quantitative characteristics of short tandem repeat (STR) variations deduced on the basis of the number of STRs that are beneficial for human survival. The longevity group included 60 nonagenarian subjects, and the control group included 250 reference adults (age, 20-50 years). Alleles of 15 Combined DNA Index System STR loci were determined using a commercial polymerase chain reaction kit. An STR with the highest frequency distribution in a population (control group) was considered as a conservative STR, and the number of core unit repeats of this STR allele was considered as the median repeat number in the STR locus (STRm). The absolute difference between the STRm and the number of core unit repeats of other STR alleles can be considered as the quantitative marker of variation for that particular STR allele (M value). The mean M values of CSF1TPO in the longevity group were significantly higher than those in the control group (P < 0.05). These findings appear to suggest that at least one of the STR loci may be associated with longevity. The M value of STR may be a new and high-efficacy genetic marker. PMID- 20582732 TI - Prognostic and predictive biomarkers in renal cell carcinoma. AB - With the recent advances in targeted therapies, biomarkers in renal cell carcinoma (RCC) continue to be developed. Historically, information regarding prognosis has come from clinicopathologic variables, however in recent years much research has focused on the molecular basis of renal cell cancer. The discovery of reliable biomarkers in RCC could have an important impact on diagnosis, prognosis, and prediction of therapeutic benefit. To date, most biomarker research has centered on byproducts of the von Hippel-Lindau (VHL) pathway including VHL mutations, vascular endothelial growth factor (ligands and receptors), hypoxia-inducible factor, and carbonic anhydrase IX. This review examines these potential biomarkers, biomarker prognostic models, and molecular expression profiles in the field of renal cell carcinoma. PMID- 20582733 TI - A rare case of primary seminoma of the small bowel with lymph node involvement. AB - INTRODUCTION: One thousand four hundred new cases of testicular cancer are diagnosed annually in the UK, with peak incidence in men aged 25-35 years old. Seminomas account for over 40% of cases. The involvement of the gastrointestinal tract with seminoma is unusual. CASE DESCRIPTION: We present a rare case of primary seminoma of the small bowel with lymph node involvement in a 30-year-old man who presented with iron deficiency anaemia and non-specific postprandial abdominal pain. A computed tomographic scan revealed small bowel wall thickening and mesenteric lymphadenopathy. Laparoscopic jejunal resection was performed and subsequent histology confirmed the diagnosis of primary seminoma of the small bowel. The patient also received three courses of cisplastin-based chemotherapy with good therapeutic outcome. DISCUSSION: The possible anatomical origins of the seminoma include: the small bowel itself, a result of anomalies during embryogenesis, location of the lymphatic drainage of the testis, an occult testicular metastasis or a viable metastasis from a primary testicular lesion which had already regressed. CONCLUSION: The investigation of unexplained iron deficiency anaemia in a young male patient requires full investigation of the entire gastrointestinal tract. PMID- 20582735 TI - Backbone assignment of the catalytic core of a Y-family DNA polymerase. AB - Sulfolobus solfataricus DNA polymerase IV (Dpo4), a model Y-family DNA polymerase, bypasses DNA lesions. Here, we report the assignments for the backbone nitrogen, carbon, and amide proton NMR signals of Dpo4's catalytic core consisting of the finger, palm, and thumb domains. Our work provides the basis for further NMR spectroscopic studies of the interactions among Dpo4, DNA, and an incoming nucleotide. PMID- 20582734 TI - Hypertension management and microvascular insulin resistance in diabetes. AB - Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes. PMID- 20582736 TI - CD-NP: an innovative designer natriuretic peptide activator of particulate guanylyl cyclase receptors for cardiorenal disease. AB - The natriuretic peptide (NP) family consists of structurally similar, although physiologically distinct, peptides that play an important role in cardiorenal homeostasis. CD-NP is a novel chimeric natriuretic peptide developed by the Mayo Clinic, in which the 15-amino acid COOH-terminus of dendroaspis NP is fused to C type NP. CD-NP is a dual activator of NP receptors A and B, and therefore, possesses the strong antiproliferative and antifibrotic properties of C-type NP with the potent natriuretic, diuretic, and aldosterone-inhibiting properties of dendroaspis NP. CD-NP has favorable cardiorenal properties when compared to recombinant B-type NP (nesiritide), including preservation of glomerular filtration rate with minimal blood pressure-lowering effects. Thus, CD-NP has emerged as an appealing novel therapeutic strategy for heart failure. The endogenous NP system, the development rationale for CD-NP, as well as in vitro, animal, and human studies and future directions will be reviewed. PMID- 20582738 TI - Application of drastic model and GIS: for assessing vulnerability in hard rock granitic aquifer. AB - Geographic information system (GIS) has become one of the leading tools in the field of hydrogeological science that helps in assessing, monitoring, and conserving groundwater resources. Groundwater is a finite resource, which is being overexploited due to increase in demand over the years leading to decrease in its potentiality. In the present study, DRASTIC model has been used to prepare groundwater vulnerable zone in hard rock aquifer of granitic terrain. The main objective is to determine susceptible zone for groundwater pollution by integrating hydrogeological layers in GIS environment. The layers such as depth of aquifer, recharge, aquifer yield, soil type, topography, vadose zone, and transmissivity are incorporated in the DRASTIC model. The final output of the map shows that around 60% of the area falls under low to no risk of pollution zone. The high risk of pollution zones are mostly present towards the margin of southeastern periphery. The lower part of the basin as well as small area on northern side falls under moderate risk of pollution zone. For the assessment of groundwater pollution zone, 24 groundwater samples have been collected from different vulnerable zones. The chemical analysis of sample shows that the southeastern margin of basin has relatively high concentration of nitrate as compared to other parts of the basin. It is present in high pollution zone as well as moderate pollution zone. The present model can be used for assessment and management of groundwater. PMID- 20582739 TI - Adsorption study of 14C-paraquat in two Malaysian agricultural soils. AB - The adsorption equilibrium time and effects of pH and concentration of (14)C labeled paraquat (1,1(')-dimethyl-4,4(')-bipyridylium dichloride) in two types of Malaysian soil were investigated. The soils used in the study were clay loam and clay soils from rice fields. Equilibrium studies of paraquat in a soil and pesticide solution were conducted. Adsorption equilibrium time was achieved within 2 h for both soil types. The amount of (14)C-labeled paraquat adsorbed onto glass surfaces increased with increasing shaking time and remained constant after 10 h. It was found that paraquat adsorbed by the two soils was very similar: 51.73 (clay loam) and 51.59 MU g g(-1) (clay) at 1 MU g/ml. The adsorption of paraquat onto both types of soil was higher at high pH, and adsorption decreased with decreasing pH. At pH 11, the amounts of (14)C-labeled paraquat adsorbed onto the clay loam and clay soil samples were 4.08 and 4.05 MU g g(-1), respectively, whereas at pH 2, the amounts adsorbed were 3.72 and 3.57 MU g g(-1), respectively. Results also suggested that paraquat sorption by soil is concentration dependent. PMID- 20582737 TI - Pathogenesis of diffuse large B cell lymphoma. AB - Substantial additional insight has been obtained in the past decade regarding the pathogenesis of diffuse large B cell lymphoma (DLBCL). Distinct subtypes of DLBCL have been defined by gene expression profiling (GEP) and they differ not only in GE profiles but also in the pattern of genetic abnormalities. The ability to correlate corresponding genetic and GEP data markedly facilitates the identification of target genes in regions with copy number abnormalities. Oncogenic pathways are often differentially activated in these different subtypes of DLBCL, suggesting that therapy should be targeted according to these differences. The tumor microenvironment plays a significant role in determining outcome and may be a novel target for therapy. The role of microRNA in lymphomagenesis is increasingly being recognized and mutation of key genes has been demonstrated to drive the activation of the NF-kappaB pathway and B cell receptor signaling. The pace of discovery will be even more rapid in the near future with the convergence of data from multiple complementary genome-wide studies and technological innovations including the rapid advance in the technology of high-throughput sequencing. PMID- 20582740 TI - Assessment of the variability in response of radish and brinjal at biochemical and physiological levels under similar ozone exposure conditions. AB - The present investigation was done to evaluate the effects of ambient air pollutants on physiological and biochemical characteristics of radish (Raphnus sativa L. var. Pusa Reshmi) and brinjal (Solanum melongena L. var. Pusa hybrid-6) plants grown in open-top chambers with filtered (FCs) and non-filtered (NFCs) treatments at a suburban site in Varanasi, India. Eight hourly mean concentrations of 11.8, 20.8, and 40.8 ppb for SO2, NO2, and O3, respectively, were recorded. O3 was the most significant pollutant affecting the plant performance. Photosynthetic rate and stomatal conductance declined in both the test plants in NFCs as compared to FCs. Lipid peroxidation was higher in NFCs, but the increase was more in radish compared to brinjal. The constitutive levels of the antioxidants as well as their increments upon O3 exposure were of higher magnitude in brinjal as compared to radish. Reduction in Fv/Fm ratio of the plants in NFCs was a regulatory mechanism to cope with the inefficiency of Calvin cycle. The data indicate that O3 triggered the protective mechanisms in plants which resulted in increments in enzymatic and non-enzymatic antioxidants of O3 exposed plants. The variability of the magnitude of responses in radish and brinjal due to O3 stress suggests that radish is more susceptible to ambient O3 injury compared to brinjal. PMID- 20582742 TI - Efficient enzymatic production of the bacterial second messenger c-di-GMP by the diguanylate cyclase YdeH from E. coli. AB - Cyclic di-GMP (c-di-GMP) is an almost universal bacterial second messenger involved in the regulation of cell surface-associated traits and the persistence of infections. GGDEF and EAL domain-containing proteins catalyse c-di-GMP synthesis and degradation, respectively. We report the enzymatic large-scale synthesis of c-di-GMP, making use of the GGDEF domain-containing protein YdeH from Escherichia coli. Overexpression and purification of YdeH have been established, and the conditions for c-di-GMP synthesis were optimised. In contrast to the chemical synthesis of c-di-GMP, enzymatic c-di-GMP production is a one-step reaction that can easily be performed with the equipment of a standard biochemical lab. The protocol allows the production of milligram amounts of c-di GMP within 1 day and paves the way for extensive biochemical and biophysical studies on c-di-GMP-mediated processes. PMID- 20582741 TI - Pharmacologic approaches for the management of symptoms and cardiovascular consequences of obstructive sleep apnea in adults. AB - INTRODUCTION: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, arousals from sleep, and daytime sleepiness. Accumulating evidence indicates that hypoxemia and sleep disruption contribute to the development of cardiovascular abnormalities in OSA. OSA is effectively treated with continuous positive airway pressure (CPAP) therapy that splints open the airway during sleep. Studies have shown that CPAP therapy improves daytime sleepiness and attenuates cardiovascular abnormalities in patients with OSA. However, not all patients with OSA tolerate or adhere to CPAP therapy. Even patients who regularly use CPAP therapy may have a few hours each night exposed to the negative effects of untreated OSA. As a result, complementary pharmacologic therapies that can be used with CPAP therapy have the potential to reduce symptoms and consequences of OSA. DISCUSSION: The wake-promoting medications modafinil and armodafinil effectively improve residual sleepiness in patients treated with CPAP therapy. Although results are equivocal so far, modafinil and armodafinil may also improve quality of life and global clinical condition in patients with OSA and residual sleepiness treated with CPAP therapy. Pharmacologic therapies also have the potential to be used with CPAP therapy to minimize cardiovascular perturbations and risk of cardiovascular disease. Preliminary studies suggest that inhibition of the enzyme xanthine oxidase and inhibition of sympathetic nervous system overactivity may have therapeutic potential to reduce cardiovascular harm in patients with OSA. CONCLUSION: Future studies of pharmacologic therapies to reduce symptoms and cardiovascular consequences of OSA should be increasingly performed as our understanding of the mechanisms mediating the adverse effects of OSA continues to evolve. PMID- 20582743 TI - The dysfunctional gut. AB - After many decades debating whether the clinical manifestations of patients with functional digestive symptoms originate "in their minds" or "in their guts," arguments remain strong on both sides of the controversy. However, advances in understanding of gut physiology and pathophysiology, and persuasive evidence on the bidirectionality of the regulatory traffic between the enteric and central nervous systems, are helping to characterize clinical situations in which we can legitimately speak of gut dysfunction, as opposed to others where symptoms are not associated with apparent or detectable gut disturbances and may truly represent somatization of an affective disorder. In this review, we describe available clinically applicable technology, albeit in specialized clinical research units, that may be used to discern whether or not challenging patients have gut sensory or motor disturbances. The practical yield of applying such methods to diagnostic investigation may be substantial, because it establishes a plausible mechanism of disease that may be used in patient management and patient persuasion, to remove uncertainties and to prevent futile repetition of conventional diagnostic tests. By evolving from symptom analysis to mechanism based diagnosis, our gastroenterology community may progress toward the goal of delivering the full diagnostic spectrum from altered morphology to disturbed function. PMID- 20582744 TI - Cerebellum atrophy and development of a peripheral dysgraphia: a paediatric case. AB - Two types of dysgraphia may be distinguished: the core ones, which reflect damage to the linguistic orthographic routes, and the peripheral ones, produced by alterations in the selection or execution of graphic motor patterns. We report the case of an 8-year-old male child, who consulted specialists due to difficulties in writing, with a background of acute cerebellar swelling at the age of 4. The writing pattern he has developed shows characteristic errors of a peripheral dysgraphia. The magnetic resonance imaging taken during the neuropsychological evaluation shows a mild atrophy in the cerebellum cortex. Our case is similar to previous studies of adult patients and equally supports the fact that the functional network responsible for the peripheral control of writing abilities may include the cerebellum, which not only maintains previously learnt writing processes but is also involved in the evolutionary acquisition of this ability. PMID- 20582745 TI - [Is postoperative pain only a nociceptive pain?]. AB - More than 75% of patients undergoing surgery suffer from acute pain. Most of this pain transforms into chronic pain. Currently, treatment of postoperative pain is based mainly on opioids, but results are not quite satisfactory. Postoperative pain is defined as a condition of tissue injury together with muscle spasm after surgery. Recently, peripheral and central sensitization has been shown within the mechanisms of postoperative pain generation. Accordingly, anti-convulsive drugs have been used successfully for the treatment of postoperative pain. Therefore, the issue of whether postoperative pain is purely a nociceptive pain remains a topic of debate. Considering that every surgical intervention might result in a nerve injury, it is not surprising to find neuropathic pain features within the postoperative pain itself. In light of these findings, it would be more precise to define postoperative pain as a combination of inflammatory and neuropathic components instead of as pure pain. Thus, the appropriate postoperative treatment should be planned involving both of these components. PMID- 20582746 TI - Effects of ketamine added to ropivacaine in pediatric caudal block. AB - OBJECTIVES: We aimed to determine the hemodynamic effects and postoperative pain control quality of ropivacaine and ketamine addition to ropivacaine in children undergoing inguinal hernia repair with caudal anesthesia. METHODS: A total of 45 patients (1-4 years) scheduled to undergo inguinal hernia repair were studied. Anesthesia was induced with sevoflurane in O2/N2O and vecuronium was administered to facilitate endotracheal intubation. Anesthesia was maintained with sevoflurane in O2/N2O. Patients were randomly divided into three groups. Following endotracheal intubation, we administered 2 mg/kg 0.2% ropivacaine to Group R; 0.5 mg/kg ketamine to Group K; and 2 mg/kg 0.2% ropivacaine plus 0.5 mg/kg ketamine to Group R+K caudally. Pain levels were evaluated via modified CHEOPS, and sedation levels were assessed by the Wilson Sedation Scale. RESULTS: At the postoperative 45th minute (min), the CHEOPS score was significantly higher in Group R compared to Group K and Group R+K (p<0.05). This score was significantly higher in Group R than in Group R+K at the postoperative 60th min (p<0.05). The effective analgesic period was significantly higher in Group K (852+/-309 min) and Group R+K (1032+/-270 min) than in Group R (435.5+/-273 min) (p<0.05). The analgesic requirement in the first 24 hours postoperatively was lower in Group R+K than the other groups. Sedation scores were below 2 in all groups. There were no significant differences between groups regarding adverse events. CONCLUSION: The results of the present study indicate that caudal ropivacaine, ketamine and ropivacaine plus ketamine provided effective postoperative analgesia. Additionally, ketamine combined with ropivacaine lengthened the duration of analgesia while lowering analgesic requirements. PMID- 20582747 TI - Comparison of emotional status and physical activity between women with chronic widespread pain and fibromyalgia. AB - OBJECTIVES: This study was conducted to compare the emotional status and physical activity level in women with chronic widespread pain (CWP) and fibromyalgia (FM). METHODS: Thirty-three women with CWP above the waist, including the upper extremities, and 68 women with FM were evaluated. To determine physical and emotional status, the Fibromyalgia Impact Questionnaire (FIQ), the Experience of Physical Activity Instrument, the Leisure Time Physical Activity Instrument, the Physical Activity at Home and Work Instrument, and the Hospital Anxiety and Depression Scale (HADS) were used. RESULTS: The CWP group had higher physical impairment scores than the FM group (p<0.05); however, the women with FM reported that they felt worse during the previous week than the other group before the interview. They also had higher scores for pain, morning tiredness and depression (FIQ 5, 7 and 10). Emotional symptoms were significantly elevated in FM patients versus the CWP patients. Conversely, no significant differences were found between the groups concerning the health status (FIQ-total) and physical activity (p>0.05). The results indicate that increased pain intensity and spread of pain have negative effects on both physical functioning and emotional status. CONCLUSION: The women with FM reported much more severe clinical symptoms than those with CWP. Therefore, in addition to physical functioning, the emotional status of women with chronic pain should also be evaluated. PMID- 20582748 TI - [Content analysis of websites directed to low back pain]. AB - OBJECTIVES: In this study, we aimed to evaluate the websites directed at providing information about low back pain with respect to their content and quality. METHODS: The websites were detected by scanning the words 'low back pain' from the Turkish pages module of the Google search portal. One hundred and fifty websites introduced on the first 20 pages were evaluated; the 65 websites determined to fulfill the desired criteria were analyzed in detail. RESULTS: Twenty of the 65 websites were excluded due to low quality, extraction from another website, sales promotion-related books/products, or qualified as news. In the majority of websites, no site administrator was indicated. When an administrator was indicated, the common specialities were physical therapists (13%), neurosurgeons (8%) and anesthesiologists (4%). Ten of the websites (22%) provided a pain definition close to international standards, whereas pain classification was available on most of the websites (84%). There was no mention of methods of pain scoring on any of them. Treatment modalities for which information was given included mostly behavioral, physical and pharmacological therapies, respectively. Complementary techniques, in order, included acupuncture, yoga and bioenergy. On 10 websites, text was supported with medical photographs, and videos were available on two. None of the websites had a provision for selection of other languages. CONCLUSION: Websites directed to low back pain should be enriched with respect to scientific content, thereby serving to increase the level of social education related to pain management. PMID- 20582749 TI - [The effects of the administration of subfacial levobupivacaine infusion with the ON-Q pain pump system on postoperative analgesia and tramadol consumption in cesarean operations]. AB - OBJECTIVES: In this study, the effects of administration of subfacial levobupivacaine infusion with the ON-Q pain pump system were investigated in elective cesarean operations for postoperative pain control and tramadol-sparing effect. METHODS: Fifty ASA I-II patients scheduled for cesarean operation were enrolled into this study. Patients were randomly divided into two groups: Group I served as a control group, without the ON-Q pain pump system, whereas Group II received the ON-Q pain pump system with subfacial 0.25% levobupivacaine infusion for 24 hours at 4 ml/hour. All patients received a standard anesthetic protocol. At the end of the surgery, all patients received tramadol i.v. Via a PCA (Patient Controlled Analgesia) device. Pain scores were assessed at 2, 6, 12 and 24 hours postoperatively. Tramadol consumption and adverse effects were noted in the first 24 hours following surgery. RESULTS: The pain scores were significantly lower in the levobupivacaine group when compared with the control group (p<0.05). The cumulative tramadol consumption was lower in the levobupivacaine group than in the control group (p<0.05). Group II used less antiemetic and had less postoperative nausea and vomiting, and the difference was statistically significant (p<0.05). CONCLUSION: No complication occurred as a result of the ON Q pain pump system. Subfacial levobupivacaine infusion with the ON-Q pain pump system diminished postoperative pain and the need for tramadol use following cesarean operations. PMID- 20582750 TI - [Burnout in healthcare workers in the Anesthesiology and Algology Departments in the Middle Anatolian region of Turkey]. AB - OBJECTIVES: Anesthesiology and Algology healthcare workers work under difficult conditions a majority of the time, and their physical and mental status must be determined in order to improve working conditions. In this study, the main goal was to evaluate the burnout level of Anesthesiology and Algology healthcare workers in the Middle Anatolian region of Turkey. METHODS: A questionnaire was sent to Anesthesiology and Algology healthcare workers of hospitals with an Algology clinic in the Middle Anatolian region and were returned by e-mail in March and April 2008. In the questionnaire, descriptive features and the Turkish validated Maslach burnout inventory (MBI) were evaluated. The MBI has 3 aspects: emotional exhaustion (EE), depersonalization (D) and personal accomplishment (PA). All questionnaires were evaluated by SPSS 11.5 program. RESULTS: 113 people were enrolled, of whom 18.8% (21) were specialist doctors and 41.1% (46) were residents. Among the doctors, the mean daily and weekly working periods were 10.3+/-2.3 and 61.3+/-19 hours, respectively. The period spent by doctors in Algology was 100% in 9.6%, 75% in 9.7% and 25% in 61.5%. Working conditions were evaluated, and 20.9% of healthcare workers were unsatisfied with the physical conditions, 19.3% with the working period and 52.5% with wages. MBIs in doctors were calculated as EE 14.7+/-5, D 5.7+/-3.5, and PA 21.6+/-4.2. CONCLUSION: This study revealed similar high burnout scores among healthcare workers, which reflect a serious burnout in the Anesthesiology and Algology group in Turkey. Burnout may be affected by dissatisfaction with working conditions. Improvement in physical conditions and reorganization to achieve psychological support might be helpful towards improving the health of healthcare workers. PMID- 20582751 TI - [Pasha-Cath in the treatment of post-thoracotomy pain syndrome]. AB - Post-thoracotomy pain syndrome is a chronic pain syndrome and is seen in approximately 5-65% of patients after thoracotomy. Post-thoracotomy pain syndrome is generally considered to be neuropathic pain due to intercostal nerve injury. A 21- year-old male patient experienced pain radiating along the incision after the thoracotomy operation. Allodynia and hyperalgesia were determined in the upper part of the incision; visual analogue scale (VAS) score was 10. Gabapentin and amitriptyline were started as medical treatment. Three months later, the patient complained of concentration difficulty at work and in daily life. Medical therapy was planned again. In view of the persisting complaints, epidural pulse radio frequency with Pasha-Cath was scheduled. After 3 weeks and also at 3 months, the VAS was 2. After 6 months, VAS remained at 2. As a result, we concluded that epidural pulse radio frequency with Pasha-Cath is an alternative and effective choice of treatment in post-thoracotomy pain syndrome when the medical treatment alone is not sufficient. PMID- 20582752 TI - An exploration of factors influencing adherence to highly active anti-retroviral therapy (HAART) among people living with HIV/AIDS in Northern Thailand. AB - This paper presents the first of a three-phase study exploring the experiences of people living with HIV/AIDS (PLWHA) in Northern Thailand. The principal aim of the study was to gain an in-depth understanding of the factors contributing to adherence in patients taking highly active anti-retroviral therapy (HAART). These insights were used in phase two to inform a number of interventions aimed at improving medication adherence in patients commencing HAART for the first time. The study comprised a cohort of 32 PLWHA over the age of 18 years who had taken HAART for at least three months. Both qualitative and quantitative methods were used. The qualitative component used a multiple case study approach to explore and describe the experiences of patients receiving HAART. The quantitative component comprised the Morisky Medication Adherence Scale and a demographic survey of the respondents. This demographic data were used to provide descriptive statistics of the research population and assist with the interpretation of the qualitative data. The findings identified a number of social, clinical, and economic factors influencing adherence to HAART. These findings led to a number of recommendations that health care providers and policy-makers can implement to improve medication adherence rates in patients taking HAART. The findings demonstrated that improved adherence not only led to improved clinical outcomes, but also the overall quality of life of PLWHA. PMID- 20582753 TI - Partner involvement in perinatal care and PMTCT services in Mbeya Region, Tanzania: the providers' perspective. AB - Partner involvement is considered to increase the effectiveness of female oriented services for sexual and reproductive health (SRH), like those for antenatal care (ANC) or the prevention of mother-to-child transmission of HIV (PMTCT). However, male participation rates remain mostly low, and previous research has identified restrictive provider attitudes among barriers for partner participation in such services. Individual perspectives and experiences of healthcare providers are assumed to significantly influence the quality of delivered services. This study aimed at exploring providers' attitudes regarding partner involvement in ANC/PMTCT and other SRH services. A hundred interviews based on a semi-structured questionnaire were conducted among healthcare providers employed in an ANC-based PMTCT program in Mbeya Region, Tanzania. Interviewees expressed overall approval of male partner integration into the services, but this approval decreased when specifying for different service types, especially in those related to perinatal examinations or labor and delivery. Divergence between general attitudes and self-reported individual behavior was observed, querying the reliability of expressed attitudes. Among providers having at least one child, personally experienced partner attendance and approval of partner involvement were significantly associated for most service types. Although general views on partner involvement in SRH services seem to be mostly supportive, there is a need for health services to strengthen providers' positions toward male involvement, for example by communicating clear policies and job guidelines, and by encouraging partner service attendance among providers themselves. PMID- 20582754 TI - Coping strategies as mediators of the relationship between sense of coherence and stress reactions: Israeli adolescents under missile attacks. AB - This study aimed to explore the relationships between sense of coherence (SOC) and stress reactions as mediated by cognitive appraisal and coping strategies among adolescents facing the acute stressful situation of missile attacks. Employing the Salutogenic Model and the interactionist approach to coping, we asked what the roles of situational factors such as coping strategies and cognitive appraisal were in mediating the relationship between SOC and stress reactions. Data were gathered during January 2009 when hundreds of missiles fell in southern Israel. One hundred and thirty eight adolescents filled out questionnaires dealing with SOC, cognitive appraisal (endangerment feelings), Adolescent Coping Scale, state anxiety, state anger, and psychological distress. Overall, our model explained 55% of the variance in stress reactions. SOC had the strongest total direct and indirect effects. Previous findings have indicated SOC as playing only a limited role in explaining stress reactions in acute stress situations. The results of this study highlight the potential of SOC as a powerful resilience factor even in an acute situation, through mediation of situational factors. PMID- 20582755 TI - The effects of physiological arousal on cognitive and psychomotor performance among individuals with high and low anxiety sensitivity. AB - Information-processing models of anxiety posit that anxiety pathology is associated with processing biases that consume cognitive resources and may detract from one's ability to process environmental stimuli. Previous research has consistently indicated that high anxiety has a negative impact on cognitive and psychomotor performance. Anxiety sensitivity, or the fear of anxiety and anxiety-related arousal sensations, is an anxiety vulnerability factor that has been shown to play a role in the development and maintenance of panic attacks and panic disorder. However, relatively little is known regarding the potential impact of anxiety sensitivity on performance. In the present study, 105 college students who scored either high (>= 24) or low (<= 14) on the Anxiety Sensitivity Index were randomly assigned to complete a series of arousal-induction tasks or no activity, followed immediately by three cognitive and psychomotor performance tasks: digit span - backward, math fluency, and grooved pegboard. Results indicated that participants with high anxiety sensitivity performed comparably to individuals with low anxiety sensitivity on each task, regardless of arousal level. PMID- 20582756 TI - "...Not just a minor thing, it is something major, which stops you from functioning daily": quality of life and daytime functioning in insomnia. AB - According to diagnostic manuals, insomnia is a 24-hr disorder, impairing important aspects of daytime functioning. There is, however, little published work describing the impact of insomnia on important areas of functioning or, indeed, the experience of living with chronically disturbed sleep on a daily basis. This study recruited 11 volunteers with persistent insomnia to take part in 1 of 3 focus-group discussions, exploring the typical daytime consequences of poor sleep and impact on quality of life (QoL). A sub-sample (n = 8) were also asked to keep an audio-diary for 7 days--appraising sleep quality and subsequent daytime functioning. Interpretative phenomenological analysis (IPA) of transcripts produced 3 superordinate themes: "just struggle through," "isolated, feeling like an outsider," and "insomnia as an obstruction to the desired self." Participants described daily difficulties with cognitive, emotional, and physical functioning; this had the cumulative effect of reducing work performance and social participation, as well as limiting life aspirations. Participants also described feeling isolated because of their disorder; this was precipitated by a lack of understanding from others and experiences with health care providers. Important novel data were generated on the proximal and distal impact of insomnia, indicating that chronically disturbed sleep can seriously limit overall QoL. PMID- 20582757 TI - Attrition and adherence in the online treatment of chronic insomnia. AB - This study examined the ability of the Theory of Planned Behavior (TPB; Ajzen, 1985) and the Transtheoretical Model of Behavior Change (TTM; Prochaska & DiClemente, 1983) to explain adherence and attrition in an online treatment program for chronic insomnia. Responses to questionnaire measures of the TPB and TTM were used to predict adherence and dropout over the subsequent 5 weeks of treatment. Results showed that there was a 17% dropout rate and that perceived behavioral control, social support, and intention to complete the program were significantly associated with adherence to sleep hygiene homework. Attrition was predicted only by symptom severity and psychiatric comorbidity. Implications are that these models should be considered to maximize adherence. PMID- 20582758 TI - Applying principles of good practice for translation and cross-cultural adaptation of sleep-screening instruments in children. AB - With the increase in the number of international projects in pediatric sleep medicine, the need to adapt sleep-screening tools for use in cross-cultural settings has rapidly grown. However, accepted procedures for translating and adapting existing measures are not uniformly and consistently incorporated in epidemiologic studies, resulting in potential measurement problems. The aims of this brief report are to (a) give an overview of principles for the translation and cultural adaptation of pediatric sleep-screening instruments and (b) illustrate these procedures in describing the translation and adaptation of two widely used pediatric sleep-screening tools for a German population. Challenges in the development of cross-cultural adaptations of parent-report sleep-screening measures for children are also discussed. PMID- 20582759 TI - Sleepiness and health in midlife women: results of the National Sleep Foundation's 2007 Sleep in America poll. AB - The 2007 Sleep in America poll, a random-sample telephone survey, provided data for this study of sleep in community-dwelling women aged 40 to 60 years. The majority of the respondents were post- or perimenopausal, overweight, married or living with someone, and reported good health. A subsample (20%) reported sleepiness that consistently interfered with daily life; the sleepy subsample reported more symptoms of insomnia, restless legs syndrome, obstructive sleep apnea, depression and anxiety, as well as more problems with health-promoting behaviors, drowsy driving, job performance, household duties, and personal relationships. Hierarchical regression showed that sleepiness along with depressive symptoms, medical comorbidities, obesity, and lower education were associated with poor self-rated health, whereas menopause status (pre-, peri- or post-) was not. These results suggest that sleep disruptions and daytime sleepiness negatively affect the daily life of midlife women. PMID- 20582760 TI - Clinical management of behavioral insomnia of childhood: treatment of bedtime problems and night wakings in young children. AB - Behavioral insomnia of childhood (BIC; more commonly known as bedtime problems and night wakings) commonly occurs in young children (0.9945. The recoveries were 83.4-112.3% with good coefficients of variation of 2.0-10.8%. The limits of detection were between 0.3 and 1.4 ng g(-1) for the six Sudan dyes, and between 3.7 and 6.0 ng g(-1) for Para Red. The limits of quantification were between 0.9 and 4.8 ng g(-1) for the six Sudan dyes, and between 12.2 and 19.8 ng g(-1) for Para Red. PMID- 20582781 TI - Determination of furan in jarred baby food purchased from the Spanish market by headspace gas chromatography-mass spectrometry (HS-GC-MS). AB - The aim of this paper is to offer a method based on headspace gas chromatography mass (HS-GC-MS) spectrometry technique in-house validated and use to estimate furan concentrations in jarred baby-food samples purchased from the Spanish market. The validation was performed according to ISO 17025 and European Food Safety Authority (EFSA) requirements and the results obtained (limit of detection (LOD) = 0.05 microg kg(-1); limit of quantification (LOQ) = 4 microg kg(-1), lowest validated level; relative standard deviation (RSD) = 3.1-10.5%; recoveries = 85.4-101.5%) confirm that this method is fit for the routine analysis of furan in jarred baby food control. Furan was analysed in 39 different baby-food samples and the mean levels varied between 64.6 microg kg(-1) (rice and chicken samples) and less than or equal to the LOQ (fruit-based samples). The mean concentrations found for the different matrices were 5.0, 37.8, 25.2, 33.8 and 30.5 microg kg( 1) for fruit, vegetables, meat/vegetables, fish/vegetables and dairy-containing baby foods, respectively. According to the statistical analyses, fruit-based baby food samples had significantly lower concentrations of furan. Mean values for the other matrices were at least five times higher, and this is in accordance with the levels reported in other studies. PMID- 20582782 TI - Innovation to improve health care provision and health systems in sub-Saharan Africa - promoting agency in mid-level workers and district managers. AB - Initiatives to address the human resource crisis in African health systems have included expanded training of mid-level workers (MLWs). Currently, MLWs are the backbone of many health systems in Africa but they are often de-motivated and they often operate in circumstances in which providing high quality care is challenging. Therefore, assuming that introducing additional people will materially change health system performance is unrealistic. We briefly critique such unifocal interventions and review the literature to understand the factors that affect the motivation and performance of MLWs. Three themes emerge: the low status and inadequate recognition of MLWs, quality of care issues and working in poorly managed systems. In response we propose three interrelated interventions: a regional association of MLWs to enhance their status and recognition, a job enrichment and mentoring system to address quality and a district managers' association to improve health systems management. The professionalisation of MLWs and district managers to address confidence, self-esteem and value is considered. The paper describes the thinking behind these interventions, which are currently being tested in Kenya, Nigeria, South Africa and Uganda for their acceptability and appropriateness. We offer the policy community a complementary repertoire to existing human resource strategies in order to effect real change in African health systems. PMID- 20582783 TI - Notes on the temperature dependence of carbon isotope fractionation by aerobic CH(4)-oxidising bacteria. AB - While the importance of environmental analyses based on isotope discrimination has been growing, uncertainties remain about underlying phenomena. Published results on the temperature dependence of carbon isotope fractionation during methane oxidation in various media show different trends. A decrease in fractionation is generally expected with temperature, but some data for methane oxidation in aqueous media show an inverse relationship. This apparent contradiction was probed by representing the first methane oxidation step as three elementary processes: the adsorption of methane on the bacterial cell wall, the desorption of methane from the wall, and the conversion of methane into methanol mediated by methane monooxygenase (MMO) enzymes. Assuming that the proportion of vacant adsorption sites is stationary, a formula for the composite fractionation factor alpha was obtained. It was shown that alpha not only expresses the fractionation that may occur in each elementary process, but that it also depends on the ratio of the kinetic rates for conversion into methanol and desorption. This result and experimental data were used to estimate the activation energy for the desorption of methane from methanotroph cell wall in aqueous medium ( approximately 200 kJ/mol). Simple Rosso models of bacterial maximal-specific growth rate were then used to demonstrate that alpha and the isotope fractionation from the MMO-mediated conversion into methanol alone could vary in opposite ways as temperature changes, but that care must be exercised when using fitted relationships across wide temperature ranges. PMID- 20582784 TI - Nitrogen isotopes determination in natural gas: analytical method and first results on magmatic, hydrothermal and soil gas samples. AB - A continuous-flow GC/IRMS technique has been developed to analyse delta(15)N values for molecular nitrogen in gas samples. This method provides reliable results with accuracy better than 0.15 per thousand and reproducibility (1sigma) within+/-0.1 per thousand for volumes of N(2) between 1.35 (about 56 nmol) and 48.9 muL (about 2 mumol). The method was tested on magmatic and hydrothermal gases as well as on natural gas samples collected from various sites. Since the analysis of nitrogen isotope composition may be prone to atmospheric contamination mainly in samples with low N(2) concentration, we set the instrument to determine also N(2) and (36)Ar contents in a single run. In fact, based on the simultaneously determined N(2)/(36)Ar ratios and assuming that (36)Ar content in crustal and mantle-derived fluids is negligible with respect to (36)Ar concentration in the atmosphere, for each sample, the degree of atmospheric contamination can be accurately evaluated. Therefore, the measured delta(15)N values can be properly corrected for air contamination. PMID- 20582785 TI - Assessment of recharge and flowpaths in a limestone thermomineral aquifer system using environmental isotope tracers (Central Portugal). AB - We conducted chemical and isotopic analyses to develop and test a hydrogeological model of thermomineral water circulation in a limestone aquifer system at Caldas da Rainha (Central Portugal), contributing to future borehole-drilling and development strategies, with the aim of extracting waters with the best possible flow and/or temperature. The thermomineral waters (T approximately 33 degrees C) discharge from springs and boreholes located close to a locally N-S-oriented oblique fault (60 degrees E) that places loamy and detritic Upper Jurassic rocks and Hettangian-Rhaetian marls (and evaporitic deposits) in contact. (14)C determinations indicate a pmC content between 29.33+/-0.14 and 44.39+/-0.20 pmC. The presence of HCO[image omitted] , Ca(2+) (and Mg(2+)) are ascribed to water limestone interactions, while Na(+), Cl(-) and SO[image omitted] concentrations are mainly associated with the dissolution of halite and gypsum lenses found along the regional syncline structure. The delta(18)O values of Caldas da Rainha thermomineral water were slightly lower than those of shallow groundwater from the Upper Jurassic rocks, suggesting the existence of two distinct aquifer systems. The different isotopic composition of water also indicates that the main recharge of the thermomineral waters likely occurs in the Middle and Lower Jurassic limestone formations of the Candeeiros Mountains. The presence of (3)H (from 1.1 to 2.8 TU) in some thermomineral borehole waters (showing rather similar geochemical signatures) suggests mixing of small amounts of shallow groundwater with thermomineral waters, as a result of leaking borehole casing construction or a recharge when the (3)H content in the atmosphere was higher than that at present. Caldas da Rainha thermomineral waters having delta(34)S(sulphate) and delta(18)O(sulphate) values between+14.9 and+19.1 per thousand and+11.1 and+16.2 per thousand, respectively, indicate that the sulphate is the result of water-rock interaction with evaporitic formations. The obtained chemical and isotopic data have informed the further development of a hydrogeological model that will be used by decision-makers, in order to contribute to the socio-economic development of the spa region. PMID- 20582786 TI - Spatial and temporal variability of stable isotopes and biological parameters for the Danube River in Serbia. AB - This paper presents the results of hydrological, physicochemical, biological, and isotopic investigations of the Danube River along the stretch through Serbian territory conducted during four campaigns in September and November 2007, September 2008 and April 2009. The stable isotope values exhibited significant changes both in the Danube (-10.7 to-9.5 per thousand for delta(18)O and-73.7 to 67.1 per thousand for delta(2)H) and in its tributaries (-9.1 to-8.5 per thousand for delta(18)O and-69.4 to-59.4 per thousand for delta(2)H) depending on the time of survey, which could be partly attributed to the influences of seasonal effects. Results emphasise the dominant role of tributaries inflows from aquifers along the Danube. The very narrow range of delta(13)C(POC) (from-28.9 to-27.4 per thousand) was associated with relatively high C/N ratios (C/N>9), and together with delta(15)N(TPN) values, the date suggested that, in early spring, a major fraction of particulate organic matter was derived from allochthonous matter. An orthogonal varimax rotation of the principal components analysis identified four latent factors ('mineral related', 'biological', 'hardness', and 'soil inlets') which are responsible for the data structure covering 79% of the observed variations among the variables studied. A reliable grouping of samples with respect to the season was found. PMID- 20582787 TI - Hekla cold springs (Iceland): groundwater mixing with magmatic gases. AB - We have analysed the chemical and stable isotope compositions of four spring waters situated just northwest of the Hekla volcano, where cold water emerges from the base of the lava flows. The stable isotope ratios of water (H, O), dissolved inorganic carbon (C) and sulphate (S) were used to determine whether magmatic gases are mixing with the groundwater. The waters can be characterised as Na-HCO(3) type. The results show that deep-seated gases mix with groundwater, substantially affecting the concentration of solutes and the isotopic composition of dissolved carbon and sulphate. PMID- 20582788 TI - Stable isotopic and geochemical variability within shallow groundwater beneath a hardwood hammock and surface water in an adjoining slough (Everglades National Park, Florida, USA). AB - Data from a 10-month monitoring study during 2007 in the Everglades ecosystem provide insight into the variation of delta(18)O, deltaD, and ion chemistry in surface water and shallow groundwater. Surface waters are sensitive to dilution from rainfall and input from external sources. Shallow groundwater, on the other hand, remains geochemically stable during the year. Surface water input from canals derived from draining agricultural areas to the north and east of the Everglades is evident in the ion data. delta(18)O and deltaD values in shallow groundwater remain near the mean of-2.4 and-12 per thousand, respectively. (18)O and D values are enriched in surface water compared with shallow groundwater and fluctuate in sync with those measured in rainfall. The local meteoric water line (LMWL) for precipitation is in close agreement with the global meteoric water line; however, the local evaporation line (LEL) for surface water and shallow groundwater is delta D=5.6 delta(18)O+1.5, a sign that these waters have experienced evaporation. The intercept of the LMWL and LEL indicates that the primary recharge to the Everglades is tropical cyclones or fronts. delta deuterium to delta(18)O excess (D(ex) values) generally reveal two moisture sources for precipitation, a maritime source during the fall and winter (D (ex)>10 per thousand) and a continental-influenced source (D (ex)<10 per thousand) in the spring and summer. PMID- 20582789 TI - (15)N natural abundance of non-fixing woody species in the Brazilian dry forest (caatinga). AB - Foliar delta(15)N values are useful to calculate N(2) fixation and N losses from ecosystems. However, a definite pattern among vegetation types is not recognised and few data are available for semi-arid areas. We sampled four sites in the Brazilian caatinga, along a water availability gradient. Sites with lower annual rainfall (700 mm) but more uniform distribution (six months) had delta(15)N values of 9.4 and 10.1 per thousand, among the highest already reported, and significantly greater than those (6.5 and 6.3 per thousand) of sites with higher rainfall (800 mm) but less uniform distribution (three months). There were no significant differences at each site among species or between non-fixing legume and non-legume species, in spite of the higher N content of the first group. Therefore, they constitute ideal reference plants in estimations of legume N(2) fixation. The higher values could result from higher losses of (15)N depleted gases or lower losses of enriched (15)N material. PMID- 20582790 TI - Stable sulphur isotope ratios in the moss species Hylocomium splendens (Hedw.) B.S.G. and Pleurozium schreberi (Brid.) Mitt. from the Kielce area (south-central Poland). AB - Stable sulphur isotope determinations were performed on 18 moss samples collected at nine sites in forested areas of the city of Kielce. The delta(34)S of Hylocomium splendens varied from 4.4 to 7.1 per thousand, whereas the delta(34)S of Pleurozium schreberi was in the range of 3.7-9.1 per thousand. The Holy Cross Mountains mosses display a positive delta(34)S signature of airborne SO(2) and sulphates of anthropogenic origin, which is characteristic for this part of Europe. Some spatial variations in the delta(34)S of mosses are due to the interactions that occur between coal combustion emissions with diverse isotopic imprints, variations in wind direction and topographic features combined with biological fractionation. PMID- 20582791 TI - The kinetic and solvent deuterium isotope effects in the 4- and 5-positions of the indole ring on the enzymatic decomposition of L-tryptophan. AB - The kinetic and solvent deuterium isotope effects in the 4- and 5-positions of the indole ring on the enzymatic decomposition of l-tryptophan catalysed by the enzyme TPase (EC. 4.1.99.1) were determined. The isotope effects were investigated by the non-competitive method using [4'-(2)H]-l-tryptophan, which was enriched in deuterium in 70% in the 4-position. The numerical values of isotope effects for 100% enrichment in deuterated label in that position were calculated by approximation. Those same isotope effects were determined for [5' (2)H]-l-tryptophan fully deuteriated in the 5' -position. PMID- 20582792 TI - Mass dependence of calcium isotope fractionations in crown-ether resin chromatography. AB - Benzo 18-crown-6-ether resin was synthesised by the phenol condensation polymerisation process in porous silica beads, of which particle diameter was ca 60micro Calcium adsorption chromatography was performed with the synthesised resin packed in a glass column. The effluent was sampled in fractions, and the isotopic abundance ratios of (42)Ca, (43)Ca, (44)Ca, and (48)Ca against (40)Ca were measured by a thermo-ionisation mass spectrometer. The enrichment of heavier calcium isotopes was observed at the front boundary of calcium adsorption chromatogram. The mass dependence of mutual separation of calcium isotopes was analysed by using the three-isotope-plots method. The slopes of three-isotope plots indicate the relative values of mutual separation coefficients for concerned isotopic pairs. The results have shown the normal mass dependence; isotope fractionation is proportional to the reduced mass difference, (M - M')/MM', where M and M' are masses of heavy and light isotope, respectively. The mass dependence clarifies that the isotope fractionations are originated from molecular vibration. The observed separation coefficient epsilon is 3.1x10(-3) for the pair of (40)Ca and (48)Ca. Productivity of enriched (48)Ca by crown-ether resin was discussed as the function of the separation coefficient and the height equivalent to the theoretical plate. PMID- 20582793 TI - Experimental plant for simultaneous production of (14)N and (15)N by (15)N/(14)N exchange in NO, NO(2)-HNO(3) system under pressure. AB - An experimental study on (14)N and (15)N simultaneous separation using the chemical exchange in NO, NO(2)-HNO(3) system under pressure is presented. The influence of the pressure and of the interstage 10 M HNO(3) flow rate on the separation of (14)N and (15)N was measured on a packed column with product and waste refluxers. At steady state and 1.8 atm (absolute), the isotopic concentration at the bottom of the separation column was 0.563 at% (15)N, and in the top of the column was 0.159 at% (15)N. The height equivalent to a theoretical plate and interstage 10 M HNO(3) flow rate values, obtained in these experimental conditions, allows the separation of (14)N highly depleted of (15)N and of (15)N at 99 at% (15)N concentration. PMID- 20582794 TI - Enzymatic synthesis of some (15)N-labelled L-amino acids. AB - Our group has developed a stereospecific enzymatic method, which is very efficient for the in vitro synthesis of l-[(15)N]serine, l-[(15)N]methionine and l-[(15)N]glutamic acid. These amino acids were prepared from the corresponding alpha -ketoacids in the suitable enzymatic systems. The bacterial NAD-dependent amino acid dehydrogenases alanin dehydrogenase, leucin dehydrogenase and glutamate dehydrogenase were used as catalysts. Glucose dehydrogenase was used for the regeneration of NADH and (15)NH(4)Cl as isotopically labelled material at 99 at.% (15)N. All reactions are inexpensive and easy to perform on a synthetically useful scale (1-10g) giving high yields of l-amino acids. The (15)N isotope content was determined by mass spectrometry. PMID- 20582795 TI - Gordon Research Conference: Isotopes in Biological and Chemical Sciences, 14-19 February 2010, Galveston, TX, USA. PMID- 20582796 TI - Amyotrophic lateral sclerosis patients show executive impairments on standard neuropsychological measures and an ecologically valid motor-free test of executive functions. AB - The study aimed to evaluate the nature and extent of executive deficits in nondemented amyotrophic lateral sclerosis (ALS) patients. A total of 22 ALS patients and 21 matched controls were compared on standard neuropsychological tests of executive functions with appropriate control for motor impairment and on an ecologically valid motor-free test of executive functions, the Medication Scheduling Task (MST). Our results show that motor dysfunction can present a significant confound when using standard neuropsychological measures; however, even when accounting for motor disabilities, ALS patients show a robust pattern of cognitive dysfunctions. Additionally, MST was shown to be a sensitive measure of cognitive impairment, providing an important insight into cognitive processes relevant for patients' daily living. PMID- 20582797 TI - A rejoinder to Lawrence (2010): it helps if you compare the correct items. PMID- 20582798 TI - Straight eye for the gay guy: composing queerness. AB - Drawing on the work of Didier Eribon and his theorization of the construction of gay male subjectivity, this article examines different "texts," broadly defined, that grapple specifically with straight men attempting to represent male homosexuality: Norman Mailer's essay, "The Homosexual Villain"; the Bravo reality television series Boy Meets Boy, and Michael Griffith's short story, "Hooper Gets a Perm." These texts represent attempts by straight authors to grapple with queer experience in ways that move the imagination of queers beyond simple stereotypes or uncritical explorations of the sexual "other." In the process of examining these texts, the following questions are addressed: What happens when a straight man attempts to represent a gay man? Does he "get it right," and is such a question even useful? More specifically, what is the value in having straights imagine queerness? Is such an imagining possible? Is such desirable? And, if so, what are the contours of such an imagining-as well as its possibilities and limitations, pedagogically, personally, and politically? Ultimately, I contend that the straight imagining of queerness offers rich potential for mutual understanding; furthermore, attempting to understand what goes into the making of those representations tells us much about how queerness circulates in our culture as a subject, a figure of discussion, contention, and representation. PMID- 20582799 TI - Barriers to optimal care between physicians and lesbian, gay, bisexual, transgender, and questioning adolescent patients. AB - The objective of this article was to identify barriers to optimal care between physicians and LGBTQ (lesbian, gay, bisexual, transgender, and questioning) adolescents. To this end, 464 anonymous, self-administered surveys were distributed in 2003 to residents and attending physicians in pediatrics, internal medicine, obstetrics-gynecology, psychiatry, emergency medicine, and family practice at Upstate Medical University. The survey included questions pertaining to practice, knowledge, and attitude pertaining to lesbian, gay, transgender, or questioning (LGBTQ) adolescents. One hundred eight four surveys were returned. The majority of physicians would not regularly discuss sexual orientation, sexual attraction, or gender identity while taking a sexual history from a sexually active adolescent. As well, the majority of physicians would not ask patients about sexual orientation if an adolescent presented with depression, suicidal thoughts, or had attempted suicide. If an adolescent stated that he or she was not sexually active, 41% of physicians reported that they would not ask additional sexual health-related questions. Only 57% agreed to an association between being a LGBTQ adolescent and suicide. The majority of physicians did not believe that they had all the skills they needed to address issues of sexual orientation with adolescents, and that sexual orientation should be addressed more often with these patients and in the course of training. This study concludes that barriers in providing optimal care for LGBTQ adolescents can be found with regard to practice, knowledge, and attitude regardless of medical field and other demographics collected. Opportunities exist to enhance care for LGBTQ adolescents. PMID- 20582800 TI - Investigating differences in public support for gay rights issues. AB - Public opinion surrounding two of the most well-known gay rights issues-same-sex marriage and adoption by gays and lesbians-varies widely: About 30% of the public favors same-sex marriage, while about 50% favors adoption. The purpose of this study was to examine and compare the demographic variables that predict attitudes toward same-sex marriage and adoption by gays and lesbians. Political ideology and attendance at religious services emerged as the strongest predictors. However, a close examination of the two issues shows that there were important differences between them. These differences may aid gay rights advocates in crafting media campaigns designed to increase support for same-sex marriage. PMID- 20582801 TI - Discrimination and victimization: parade for lesbian, gay, bisexual, and transgender (LGBT) pride, in Chile. AB - This article describes the population participating in the LGBT Pride Parade in Santiago, Chile, from discrimination and victimization standpoints. The sample consisted of 488 subjects older than 18 years (M = 25.1), who were interviewed during the 2007 event. For this purpose, a questionnaire from the Latin American Centre of Sexuality and Human Rights (CLAM) was adapted and administered. Approximately 35% of respondents reported having experimented school, religious, or neighborhood discrimination. The more discriminated are transgender people. Approximately three fourths of respondents reported experiencing ridicule and almost 60% reported experiencing insults or threats. Transgender were significantly more likely than gay men, lesbians, and bisexuals to experience discrimination or victimization events. Finally, the parade acquired an important social and political character in the context of a clearly homophobic society. PMID- 20582802 TI - Staff perceptions of same-gender sexual contacts in long-term care facilities. AB - An ongoing fear in the gay and lesbian community is that long-term care (LTC) facilities may not be sensitive to their needs. In the present study, 218 LTC staff members responded to one of three vignettes in which resident sexual contact was observed, with only the gender of the characters changing, to create different gender pairings. Results suggested that staff rated male-male and female-female pairings more negatively than heterosexual intimacy. Knowledge about older adult sexuality made little difference in staff ratings. However, staff attitudes were directly related to ratings of negative reaction and level of acceptability of same-gender sexuality. PMID- 20582803 TI - Blanchard's Autogynephilia Theory: a critique. AB - Over the last 20 years, Ray Blanchard, Ph.D., with a variety of coauthors and collaborators, has proposed a theory that links the sexual orientation of male-to female transsexuals with the presence or absence of autogynephilia (erotic arousal by the thought or image of "himself" as a woman). Blanchard's Autogynephilia Theory suggests that the association between sexual orientation and autogynephilia among male-to-female transsexuals is clinically important and the association is always (or almost always) present. Although the theory has been criticized by clinicians, researchers, and transsexuals themselves, it has not been critiqued in a peer-reviewed article previously. This article will attempt to fill that gap. Key studies on which the theory is based will be analyzed and alternative interpretations of the data presented. I conclude that although autogynephilia exists, the theory is flawed. PMID- 20582805 TI - Antigenotoxic effect of allicin against estradiol-17beta-induced genotoxic damage in cultured mammalian cells. AB - Antigenotoxic activity of allicin, one of the sulphur compounds of garlic (Allium sativum) which possesses antioxidant and thiol disulphide exchange activity, was studied against estradiol-17beta-induced genotoxic damage using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameters. Approximately 10, 20 and 40 microM of estradiol-17beta was tested for its genotoxic effect in the presence of metabolic activation and was found to be genotoxic at 20 and 40 microM. Approximately 20 microM of estradiol-17beta was treated along with 5, 10 and 15 microM of allicin, separately, in the presence of metabolic activation. Similar treatments were given with 40 microM of estradiol 17beta. Treatments along with allicin result in the reduction of CAs and SCEs, suggesting its anti-genotoxic activity in human lymphocytes in vitro against estradiol-17beta-induced genotoxic damage. PMID- 20582806 TI - Effects of tetrandrine on cAMP and cGMP levels in rabbit corpus cavernosum in vitro. AB - The aim of this study was to further investigate the relaxation mechanism of tetrandrine (Tet), a bis-benzylisoquinoline alkaloid isolated from the Chinese medicinal herb-root of Stephania tetrandra S Moore, on rabbit corpus cavernosum tissue in vitro. The effects of Tet on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded by means of (125)I radioimmunoassay. The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol mg(-1). Tet increased the cAMP concentration in a dose dependent manner (p < 0.05), but this effect was not inhibited by an adenylate cyclase inhibitor (cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine, MDL 12, 330A) (p > 0.05). The accumulation of cAMP induced by prostaglandin E(1) (PGE(1), a stimulator of cAMP production) was also augmented by Tet in a dose dependent manner (p < 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol mg(-1). Tet did not affect this concentration of cGMP, neither in the presence nor the absence of a guanyl cyclase inhibitor (1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (p > 0.05). Further, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Tet (p > 0.05). Tet, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting PDEs activity. PMID- 20582807 TI - Pharmacological activities on Ephedra nebrodensis Tineo. AB - As a part of our endeavour to screen Mediterranean medicinal plants for various pharmacological activities, we evaluated antihistaminic, adaptogenic, anti inflammatory, antinociceptive, hypotensive and locomotor properties, and antioxidant potential of Ephedra nebrodensis. (1)H-NMR spectroscopy was carried out to identify the plant metabolites, which confirmed the presence of ephedrinic skeleton alkaloids. The ethanol : acetone (1 : 1) extract exhibited dose-related antihistaminic, anti-inflammatory, antinociceptive, hypotensive, antioxidant and locomotor stimulant activity. The plant bears potential for further studies. PMID- 20582808 TI - Susceptibility of complete bacteria and spheroplasts of Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi to rolliniastatin-2. AB - Rolliniastatin-2 is an acetogenin with elevated cytotoxic activity whose effect on bacteria has not yet been analysed and was isolated by CC from the hexanic extract of Annona diversifolia Saff (Annonaceae) seeds. In this study, we evaluated the susceptibility of Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi as well as spheroplasts of these bacteria to the compound, determining percent inhibition by turbidimetry. The complete bacteria were susceptible to rolliniastatin-2 (28-40% at 2 mg mL(-1)), while spheroplasts showed an increased susceptibility (55-58%, at 1 ng mL(-1)). The most susceptible bacterium was P. aeruginosa, while the spheroplasts of E. coli and S. typhi were most sensitive to the compound's effects. PMID- 20582809 TI - A new antitumour ansamitocin from Actinosynnema pretiosum. AB - A new compound of ansamitocin was isolated from the extracts of fermentation medium of mutant strain HGF052 derived from Actinosynnema pretiosum ssp. aurantium ATCC 31565, and identified as N-demethyl-desepoxy-9-methoxy-maytansinol (1) on the basis of extensive spectroscopic methods. Bioassay results showed that compound 1 had cytotoxic activity against HL-60 and BEL-7402 cell lines. PMID- 20582810 TI - A study of the chemical composition of black cumin oil and its effect on penetration enhancement from transdermal formulations. AB - The chemical composition of the solvent extracted fixed oil of black cumin (Nigella sativa L.) seeds was determined by capillary GC and GC/MS. Thirty-two fatty acids (99.9%) have been identified in the fixed oil. The major fatty acids were linoleic acid (50.2%), oleic acid (19.9%), margaric acid (10.3%), cis-11,14 eicosadienoic acid (7.7%) and stearic acid (2.5%). The effect of black cumin oil on in vitro percutaneous absorption of the model lipophilic drug carvedilol was investigated using excised rat abdominal skin. Transdermal flux, permeability coefficient and enhancement factor were calculated for different concentrations of oil in isopropyl alcohol. Black cumin oil (5% v/v) exhibited the highest enhancement in permeation. The increase in the permeability of the drug is due to increased drug diffusivity through the stratum corneum under the influence of black cumin oil. A higher content of linoleic acid (and other unsaturated fatty acids) in the oil has been postulated to be responsible for the enhancement of in vitro percutaneous absorption of the drug. PMID- 20582811 TI - Natural products inhibit LPS-induced activation of pro-inflammatory cytokines in peripheral blood mononuclear cells. AB - Haemodialysis (HD) patients have many biochemical, immune and inflammatory alterations that can lead to an increased risk for cardiovascular disease. The two major factors affecting these disorders are (a) metabolic, biochemical, immune or inflammatory alterations due to the uremic syndrome per se and (b) alterations due to the therapeutic treatments of uremia, especially HD-induced stress. HD-induced stress includes activation of the pro-inflammatory transcription factor NF-kappaB. In the present study, we have employed lipopolysaccharide (LPS) to activate the peripheral blood mononuclear cells (PBMC), as a model of HD-induced stress. The natural products curcumin, resveratrol and parthenolide are known inhibitors of the activation of NF-kappaB. PBMCs were treated with various concentrations of curcumin, resveratrol and parthenolide and tested for the abilities of these natural products to protect against the LPS-induced expression, secretion of the pro-inflammatory cytokines TNFalpha, IL-1beta and IL-6 and activation of the pro-inflammatory COX-2. We report here that parthenolide is an especially effective natural product that limits the development of a pro-inflammatory state by preventing the activation of all four of these pro-inflammatory signals. The approach of limiting the development of a pro-inflammatory state in HD patients during the dialysis procedure by addition of a natural product that protects against activation of NF kappaB might be a clinically useful approach to protect leukocytes from HD induced stress. PMID- 20582812 TI - Evaluation of in vitro activity of carvacrol against Candida albicans strains. AB - In this study, the in vitro activity of carvacrol on 100 clinical isolates of Candida albicans was evaluated by determining the minimum inhibitory concentrations (MICs). Susceptibility of clinical isolates of C. albicans to carvacrol was determined by broth microdilution method. Carvacrol was active in vitro against all strains of C. albicans, with MICs ranging from 0.125% to 0.004%. MIC(50) and MIC(90) values of carvacrol were observed at 0.064 and 0.125 mg mL(-1), respectively. MIC and MFC values were similar for most of the tested strains. These results indicated that carvacrol inhibited the growth of C. albicans, implying its potential use in the topical treatment of C. albicans infections. PMID- 20582813 TI - Disaster in the Gulf: public health and public responsibility. PMID- 20582814 TI - Why bioethicists still need to think more about sex ... PMID- 20582815 TI - Should human beings have sex? Sexual dimorphism and human enhancement. AB - Since the first sex reassignment operations were performed, individual sex has come to be, to some extent at least, a technological artifact. The existence of sperm sorting technology, and of prenatal determination of fetal sex via ultrasound along with the option of termination, means that we now have the power to choose the sex of our children. An influential contemporary line of thought about medical ethics suggests that we should use technology to serve the welfare of individuals and to remove limitations on the opportunities available to them. I argue that, if these are our goals, we may do well to move towards a "post sex" humanity. Until we have the technology to produce genuine hermaphrodites, the most efficient way to do this is to use sex selection technology to ensure that only girl children are born. There are significant restrictions on the opportunities available to men, around gestation, childbirth, and breast-feeding, which will be extremely difficult to overcome via social or technological mechanisms for the foreseeable future. Women also have longer life expectancies than men. Girl babies therefore have a significantly more "open" future than boy babies. Resisting the conclusion that we should ensure that all children are born the same sex will require insisting that sexual difference is natural to human beings and that we should not use technology to reshape humanity beyond certain natural limits. The real concern of my paper, then, is the moral significance of the idea of a normal human body in modern medicine. PMID- 20582816 TI - Sex redux. PMID- 20582817 TI - Response to open peer commentaries on "Human dignity and transhumanism: do anthro technological devices have moral status?". PMID- 20582818 TI - The risks of "sexual normalcy". PMID- 20582819 TI - Humans should be free of all biological limitations including sex. PMID- 20582820 TI - Resisting Sparrow's sexy reductio: selection principles and the social good. PMID- 20582821 TI - Sexual dimorphism and the value of feminist bioethics. PMID- 20582822 TI - Sex and enhancement: a phenomenological-existential view. PMID- 20582823 TI - The value of sex in procreative reasons. PMID- 20582824 TI - Sexual dimorphism and sexual intermediaries. PMID- 20582825 TI - Is there a moral obligation to have children of only one sex? PMID- 20582826 TI - This is what happens when you forget about gender. PMID- 20582827 TI - Sex, romance, and research subjects: an ethical exploration. AB - Professional standards in medicine and psychology treat concurrent sexual relationships with patients as violations of fiduciary trust, and they sometimes rule out sexual relationships even after a clinical relationship is over. These standards also rule out sex with research subjects who are also patients, but what about nonclinical relationships where there are not always parallels to the standards of clinical medicine? One way to treat sex in nonclinical research relationships is to treat it as sex is treated elsewhere among adults, as a matter of individual choice and responsibility. Alternately, one could ask oversight bodies to draw lines between research that can safely accommodate sexual relationships and research that cannot. One could even ask researchers to avoid all concurrent sexual relationships with their research participants, as happens in clinical medicine. Each of these options has drawbacks that undermine its value as a definitive solution. The deficiencies of these options highlight the need for a professional code of conduct for nonclinical researchers. PMID- 20582828 TI - No sex please, we're social scientists? PMID- 20582829 TI - On the costly compromises of nonclinical research relationships. PMID- 20582830 TI - No sex please in sexuality research. PMID- 20582831 TI - Human dignity and transhumanism: do anthro-technological devices have moral status? AB - In this paper, I focus on the concept of human dignity and critically assess whether such a concept, as used in the Universal Declaration on Bioethics and Human Rights, is indeed a useful tool for bioethical debates. However, I consider this concept within the context of the development of emerging technologies, that is, with a particular focus on transhumanism. The question I address is not whether attaching artificial limbs or enhancing particular traits or capacities would dehumanize or undignify persons but whether nonbiological entities introduced into or attached to the human body contribute to the "augmentation" of human dignity. First, I outline briefly how the Universal Declaration on Bioethics and Human Rights uses the concept of dignity. Second, I look at the possibility of a universal bioethics in relation to the concept of human dignity. Third, I examine the concept of posthuman dignity and whether the concept of human dignity as construed in the declaration has any relevance to posthuman dignity. PMID- 20582832 TI - Human dignity, transhuman dignity, and all that jazz. PMID- 20582833 TI - Toward a "post-posthuman dignity area" in evaluating emerging enhancement technologies. PMID- 20582834 TI - Dignity and agential realism: human, posthuman, and nonhuman. PMID- 20582835 TI - Deciphering dignity. PMID- 20582836 TI - Inconsistency of human rights approaches to human dignity with transhumanism. PMID- 20582837 TI - Transhumanism, human dignity, and moral status. PMID- 20582838 TI - Dignity, arete, and hubris in the transhumanist debate. PMID- 20582839 TI - Dignity, posthumanism, and the community of values. PMID- 20582841 TI - An attachment perspective on incarcerated parents and their children. AB - The United States now incarcerates more people than any other country in the world (Pew Charitable Trust, 2008), and most of these incarcerated individuals have one or more children 18 years of age or younger (Glaze & Maruschak, 2008). Although the actual number is not known because the information is not systematically collected by jails, prisons, schools, child welfare agencies, or other organizations or institutions, a conservative estimate is that more than three million children are affected (Glaze & Maruschak, 2008; Western & Wildeman, 2009). In editing this special issue we had two major goals: (1) to introduce the many issues raised by parental incarceration to readers already grounded in attachment theory and research and (2) to highlight the importance of an attachment perspective to those who study and work with incarcerated parents. The contributors to this special issue present conceptual and empirical articles focusing on attachment issues related to incarcerated parents and their children. This introduction provides an overview of these contributions. PMID- 20582842 TI - Parental incarceration, attachment and child psychopathology. AB - Theory and evidence relating parental incarceration, attachment, and psychopathology are reviewed. Parental incarceration is a strong risk factor for long-lasting psychopathology, including antisocial and internalizing outcomes. Parental incarceration might threaten children's attachment security because of parent-child separation, confusing communication about parental absence, restricted contact with incarcerated parents, and unstable caregiving arrangements. Parental incarceration can also cause economic strain, reduced supervision, stigma, home and school moves, and other negative life events for children. Thus, there are multiple possible mechanisms whereby parental incarceration might increase risk for child psychopathology. Maternal incarceration tends to cause more disruption for children than paternal incarceration and may lead to greater risk for insecure attachment and psychopathology. Children's prior attachment relations and other life experiences are likely to be of great importance for understanding children's reactions to parental incarceration. Several hypotheses are presented about how prior insecure attachment and social adversity might interact with parental incarceration and contribute to psychopathology. Carefully designed longitudinal studies, randomized controlled trials, and cross-national comparative research are required to test these hypotheses. PMID- 20582843 TI - Attachment, parental incarceration and possibilities for intervention: an overview. AB - Incarceration of parents and pregnant women, which is quite common in the United States, creates problems for the incarcerated individuals' children. Here we summarize attachment research related to this issue and explain how attachment related interventions might reduce both the negative effects on children of having their parents incarcerated and the likelihood of future crime and incarceration on the part of both the adults and their children. We consider the intergenerational transmission of attachment insecurity, the practice of having an incarcerated adult's parent take custody of the children, and the multitude of problems associated with incarcerated adults' attachment insecurity (including perpetrated and received abuse, drug and alcohol problems, a history of educational and employment difficulties, and inadequate models of parenting). We discuss validated attachment intervention programs that might be used with incarcerated parents, as well as barriers to implementing such programs. PMID- 20582844 TI - Enhancing attachment security in the infants of women in a jail-diversion program. AB - Pregnant female offenders face multiple adversities that make successful parenting difficult. As a result, their children are at risk of developing insecure attachment and attachment disorganization, both of which are associated with an increased likelihood of poor developmental outcomes. We evaluated the outcomes of participants in Tamar's Children, a 15-month jail-diversion intervention for pregnant, nonviolent offenders with a history of substance abuse. All women received extensive wrap-around social services as well as the Circle of Security Perinatal Protocol (Cooper, Hoffman, & Powell, 2003). We present data on 20 women and their infants who completed the full dosage of treatment (a residential-living phase from pregnancy until infant age six months and community-living phase until 12 months). Results indicated that (1) program infants had rates of attachment security and attachment disorganization comparable to rates typically found in low-risk samples (and more favorable than those typically found in high-risk samples); (2) program mothers had levels of maternal sensitivity comparable to mothers in an existing community comparison group; and (3) improvement over time emerged for maternal depressive symptomatology, but not other aspects of maternal functioning. Given the lack of a randomized control group, results are discussed in terms of the exploratory, program-development nature of the study. PMID- 20582845 TI - Attachment organization in a sample of incarcerated mothers: distribution of classifications and associations with substance abuse history, depressive symptoms, perceptions of parenting competency and social support. AB - We report attachment classifications in a sample of pregnant women incarcerated in a state prison with a nursery program. Analyses were based on 69 women serving sentences for felony crimes who were followed from the birth of their child to completion of the prison nursery co-residence. They completed the Adult Attachment Interview shortly after entering the program and scales measuring depression, perceived parenting competency, and social support at study entry (Time 1) and program completion (Time 2). Incarcerated mothers had higher rates of insecure attachment than previous low-risk community samples. Compared with dismissing and secure mothers, preoccupied mothers reported higher levels of depressive symptoms, lower parenting competency, and lower satisfaction with social support at the conclusion of the nursery program. Higher scores on unresolved loss and derogation were associated with a history of substance abuse; higher scores on unresolved trauma were associated with depressive symptoms at program completion. PMID- 20582846 TI - Intergenerational transmission of attachment for infants raised in a prison nursery. AB - Within a larger intervention study, attachment was assessed with the Strange Situation Procedure for 30 infants who co-resided with their mothers in a prison nursery. Sixty percent of infants were classified secure, 75% who co-resided a year or more and 43% who co-resided less than a year, all within the range of normative community samples. The year-long co-residing group had significantly more secure and fewer disorganized infants than predicted by their mothers' attachment status, measured by the Adult Attachment Interview, and a significantly greater proportion of secure infants than meta-analyzed community samples of mothers with low income, depression, or drug/alcohol abuse. Using intergenerational data collected with rigorous methods, this study provides the first evidence that mothers in a prison nursery setting can raise infants who are securely attached to them at rates comparable to healthy community children, even when the mother's own internal attachment representation has been categorized as insecure. PMID- 20582847 TI - Attachment and caregiving relationships in families affected by parental incarceration. AB - This longitudinal, mixed method study focused on 57 families of children who participated in a mentoring program for children of incarcerated parents. Children ranged in age from 4 to 15 years. Monthly interviews were conducted with children, caregivers, and mentors during the first six months of program participation, and questionnaires were administered at intake and six months to assess caregiver-child and incarcerated parent-child relationships, contact with incarcerated parents, and children's behavior problems. Although some children viewed their incarcerated parents as positive attachment figures, other children reported negative feelings toward or no relationship with incarcerated parents. In addition, our assessments of children nine years old and older revealed that having no contact with the incarcerated parent was associated with children reporting more feelings of alienation toward that parent compared to children who had contact. Children's behavior problems were a primary concern, often occurring in a relational context or in reaction to social stigma associated with parental imprisonment. PMID- 20582849 TI - An analysis of hospital brand mark clusters. AB - This study analyzed brand mark clusters (i.e., various types of brand marks displayed in combination) used by hospitals in the United States. The brand marks were assessed against several normative criteria for creating brand marks that are memorable and that elicit positive affect. Overall, results show a reasonably high level of adherence to many of these normative criteria. Many of the clusters exhibited pictorial elements that reflected benefits and that were conceptually consistent with the verbal content of the cluster. Also, many clusters featured icons that were balanced and moderately complex. However, only a few contained interactive imagery or taglines communicating benefits. PMID- 20582848 TI - Parental incarceration: the challenges for attachment researchers. AB - This commentary has two parts. In the first part I highlight major theoretical issues raised by the two integrative articles, adding my own perspective and interpretations. Next I discuss selected findings from the two intervention programs designed to enhance infant-mother attachment in prison- and jail diversion nurseries and the multi-informant interview study of children's, caregivers', and mentors' comments about an incarcerated parent. I offer some additional background, queries, and what I hope to be clarifications. In the second part of this commentary, I reflect on ways in which theory and findings presented in this special issue might inform future intervention research on children of incarcerated parents and their families, briefly touching on issues related to recruitment of participants, research design, and qualitative and quantitative measures, as well as required conceptual innovations, social policy, and advocacy. PMID- 20582850 TI - Pharmaceutical counterfeiting and the RFID technology intervention. AB - Both nationally and internationally, pharmaceutical counterfeiting has become a problem that is threatening economic stability and public health. The purpose of the present research study review was to analyze the scope and severity of pharmaceutical counterfeiting and to establish if the implantation of the Radio Frequency Identification Device (RFID) model can more efficiently be used within the pharmaceutical supply chain to reduce the problem counterfeit drugs impose on public health and international economic stability. Results indicated that implementing the RFID model for tracking drugs at the item level in the pharmaceutical supply chain has potential to alleviate the scope of the counterfeit drug problem. Recommendations for how the pharmaceutical industry may sooner adopt the RFID model are made. PMID- 20582851 TI - Uncompensated care and quality assurance among rural hospitals. AB - Health care disparities in rural areas remain significant in the U.S. health care industry. Uncompensated care makes health care disparities in rural areas worse, and rural hospitals are unfavorably positioned to compete with urban hospitals in the economic-downturn marketplace. How uncompensated care affects quality care among rural hospitals has been lightly investigated. Given that many rural residents experience difficulty accessing high quality care and given the importance of establishing quality care practice standards in a rural setting, we conducted a systematic literature review to identify some quality-care barriers and opportunities and suggested strategies to strengthen the position of rural hospitals in response to uncompensated care. PMID- 20582852 TI - Electronic medical records in long-term care. AB - Long-term care (LTC) facilities possess unique characteristics in terms of implementation and utilization of electronic medical records (EMRs). The focus of LTC is on a population requiring care encompassing all aspects associated with quality of life rather than simply acute treatment. Because this focus is of a larger scale than traditional medical facilities, the priorities in the implementation and utilization of EMRs are higher in accessing patient history information. The purpose of this study was to determine the EMR utilization in the chronic care settings. In conclusion, the literature review performed does not support the fact that EMRs are currently being effectively and widely used in the LTC facilities. PMID- 20582853 TI - Transport of inorganic mercury and methylmercury in target tissues and organs. AB - Owing to the prevalence of mercury in the environment, the risk of human exposure to this toxic metal continues to increase. Following exposure to mercury, this metal accumulates in numerous organs, including brain, intestine, kidneys, liver, and placenta. Although a number of mechanisms for the transport of mercuric ions into target organs were proposed in recent years, these mechanisms have not been characterized completely. This review summarizes the current literature related to the transport of inorganic and organic forms of mercury in various tissues and organs. This review identifies known mechanisms of mercury transport and provides information on additional mechanisms that may potentially play a role in the transport of mercuric ions into target cells. PMID- 20582854 TI - The potential of selected brominated flame retardants to affect neurological development. AB - Various brominated flame retardants (BFR), including polybrominated diphenyl ether (PBDE) congeners, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), are commonly used in household items and electronics and have been detected in the environment and/or the bodily fluids of people, including children. Some studies in animals suggest that exposure to PBDE congeners, HBCD, or TBBPA during the perinatal period may affect locomotor activity and/or memory and learning. Epidemiological studies showing similar effects in humans, however, are lacking. To assess whether an association exists between perinatal exposure and development of consistent neurobehavioral alterations, published animal studies investigating perinatal exposure to PBDE congeners, HBCD, or TBBPA with specific neurobehavioral evaluations-particularly, assessments of motor activity were reviewed for consistency of results. Our analysis shows that although the majority of studies suggest that perinatal exposure affects motor activity, the effects observed were not consistent. This lack of consistency includes the type of motor activity (locomotion, rearing, or total activity) affected, the direction (increase or decrease) and pattern of change associated with exposure, the existence of a dose response, the permanency of findings, and the possibility of gender differences in response. Interestingly, Good Laboratory Practices (GLP) compliant studies that followed U.S. Environmental Protection Agency (EPA)/Organization for Economic Cooperation and Development (OECD) guidelines for developmental neurotoxicity testing found no adverse effects associated with exposure to PBDE209, HBCD, or TBBPA at doses that were orders of magnitude higher and administered over longer durations than those used in the other studies examined herein. The lack of consistency across studies precludes establishment of a causal relationship between perinatal exposure to these substances and alterations in motor activity. PMID- 20582855 TI - Providing effective supervision in clinical neuropsychology. AB - A specialty like clinical neuropsychology is shaped by its selection of trainees, educational standards, expected competencies, and the structure of its training programs. The development of individual competency in this specialty is dependent to a considerable degree on the provision of competent supervision to its trainees. In clinical neuropsychology, as in other areas of professional health service psychology, supervision is the most frequently used method for teaching a variety of skills, including assessment, report writing, differential diagnosis, and treatment. Although much has been written about the provision of quality supervision in clinical and counseling psychology, very little published guidance is available regarding the teaching and provision of supervision in clinical neuropsychology. The primary focus of this article is to provide a framework and guidance for the development of suggested competency standards for training of neuropsychological supervisors, particularly at the residency level. In this paper we outline important components of supervision for neuropsychology trainees and suggest ways in which clinicians can prepare for supervisory roles. Similar to Falender and Shafranske (2004), we propose a competency-based approach to supervision that advocates for a science-informed, formalized, and objective process that clearly delineates the competencies required for good supervisory practice. As much as possible, supervisory competencies are related to foundational and functional competencies in professional psychology, as well as recent legislative initiatives mandating training in supervision. It is our hope that this article will foster further discussion regarding this complex topic, and eventually enhance training in clinical neuropsychology. PMID- 20582856 TI - Do executive function deficits differentiate between children with attention deficit hyperactivity disorder (ADHD) and ADHD comorbid with oppositional defiant disorder? A cross-cultural study using performance-based tests and the behavior rating inventory of executive function. AB - This study examined the differential executive dysfunction of children with attention deficit hyperactivity disorder (ADHD) and those with ADHD and oppositional defiant disorder (ODD) in Han Chinese. A total of 258 children (89 ADHD, 53 ADHD + ODD, 116 controls) completed performance-based executive function tests and had their everyday life executive skills rated by their parents using the Behavior Rating Inventory of Executive Function (BRIEF). Both the ADHD and ADHD + ODD groups performed worse than the controls in the Stroop and Trail making tests and the BRIEF. The ADHD + ODD group were rated worse than the ADHD group on the BRIEF, but the two groups showed no significant difference in the performance-based tests. These findings suggest Han Chinese children with ADHD display executive dysfunction in performance-based tests and everyday life scenarios, in a similar way to findings in Western counterparts. However, children with ADHD + ODD showed more severe executive dysfunction in everyday life scenarios than those with ADHD only. PMID- 20582860 TI - Digestive Disease Week 2010. Turning Science into Medicine--part 1. AB - The Digestive Disease Week 2010 conference, held in New Orleans, included topics covering new therapeutic developments in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. This conference report highlights selected presentations on the novel thiopurine-based immunosuppressive agents B-0N and E-1 (both Giuliani SpA/Friedrich-Alexander-Universitaet Erlangen Nuernberg); the investigation of ML-3403 (c-a-i-r biosciences GmbH), a p38 MAPK inhibitor for the treatment of chronic inflammatory disease; the development of ALV-003 (Alvine Pharmaceuticals Inc) for the treatment of celiac disease; efficacy studies of AST-120 in patients with irritable bowel syndrome; and a clinical trial evaluating linaclotide (Ironwood Pharmaceuticals Inc/Forest Laboratories Inc/Astellas Pharma Inc/Almirall Prodesfarma SA) withdrawal during chronic constipation therapy. PMID- 20582861 TI - Digestive Disease Week 2010. Turning Science into Medicine--part 2. AB - The Digestive Disease Week 2010 conference, held in New Orleans, included topics covering new therapeutic developments in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. This conference report highlights selected presentations on the apolipoprotein E-mimetic peptide COG-112 (Cognosci Inc) for the potential treatment of Citrobacter rodentium-induced colitis; the inhibition of sphingosine kinase with ABC-294640 (Apogee Biotechnology Corp) to alleviate stress after hepatic ischemia-reperfusion injury; TLR4 targeting with NI-0101 (NovImmune SA) to prevent colitis-associated cancer; immunization against TNF with TNFalpha kinoid (Neovacs SA) for the treatment of patients with Crohn's disease; and preclinical studies with the anti inflammatory agent minnelide (University of Minnesota) for the treatment of pancreatic cancer. PMID- 20582862 TI - Association for Research in Vision and Ophthalmology (ARVO)--2010 Annual Meeting. For Sight: The Future of Eye and Vision Research--part 1. AB - The 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), held in Fort Lauderdale, FL, USA, included topics covering new therapeutic developments in the field of eye and vision research. This conference report highlights selected presentations on the development of FOV 2304 (Fovea Pharmaceuticals SA) for the potential treatment of diabetic macular edema; PHA-666859 (Pfizer Inc) for diabetic retinopathy; GTx-878 (GTx Inc) and FCFD-4514S (Genentech Inc) for age-related macular degeneration; SYL-040012 (Sylentis Sau) for ocular hypertension associated with open-angle glaucoma; PEG PLA-TNP-470 (Harvard Medical School) for ocular neovascularization; recombinant galectin-3 (Senju Pharmaceutical Co Ltd) for corneal injury; and CellBead Neuro (CellMed Inc) for neurological trauma and neurodegeneration. PMID- 20582863 TI - Association for Research in Vision and Ophthalmology (ARVO)--2010 Annual Meeting. For Sight: The Future of Eye and Vision Research--part 2. AB - The 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), held in Fort Lauderdale, FL, USA, included topics covering new therapeutic developments in the field of eye and vision research. This conference report highlights selected presentations on the development of OT-440 (Othera Pharmaceuticals Inc) for the potential treatment of glaucoma, an extended release implant of brimonidine (pSivida Corp) for ocular hypertension, AR-12286 (Aerie Pharmaceuticals Inc) for ocular hypertension or glaucoma, AC-8 (Calmune Corp/RiboVax Biotechnologies SA) for ocular diseases following HSV infection, and fidarestat (Sanwa Kagaku Kenkyusho Co Ltd) and the recombinant proteins NOV and NOVCter (INSERM/University Rene Descartes) for corneal neovascularization. PMID- 20582864 TI - Generics, Supergenerics and Patent Strategies--SMi's 13th Annual Meeting. AB - SMi's 13th Annual Meeting on Generics, Supergenerics and Patent Strategies, held in London, included topics covering new trends in the generics field, the difficulties faced by companies in entering the generics market and recent developments in IP. This conference report highlights selected presentations on generics in India, protecting pharmaceutical products in China, changes in generics law and litigation in the US and Europe, challenges for market selection and entry for generics companies, the influence of changes in the healthcare market on the generics industry, supergenerics, and biosimilars. PMID- 20582865 TI - Vaccine Manufacturing--Second Annual visiongain Conference. AB - The Vaccine Manufacturing--Second Annual visiongain Conference, held in London, included topics covering new technological developments in the field of influenza vaccine research. This conference report highlights selected presentations on influenza vaccine development in mammalian, insect and avian embryonic cells, regulatory considerations for cell culture-based influenza vaccine production, an improved animal model for influenza infection, and considerations for designing vaccine manufacturing facilities. Investigational drugs discussed include FluBiovax (Immunobiology Ltd) and FluBlok (Protein Sciences Corp/UMN Pharma Inc). PMID- 20582866 TI - Drug Development for Neurodegenerative Diseases--Second Annual marcus evans Conference. Advances in drug development for NDD and expediting discovery through novel compounds and sound clinical trials. AB - The Second Annual marcus evens Drug Development for Neurodegenerative Diseases Conference, held in Boston, included topics covering new therapeutic developments in the field of neurodegenerative diseases. This conference report highlights selected presentations on biomarkers for neurodegenerative diseases; novel approaches to therapy for neurodegenerative disorders, including targeting PKCepsilon in Alzheimer's disease, small-molecule therapeutics for neurogenesis, neureglins to promote neurorecovery, and updates on several investigational drugs; and progress in neurodegenerative disease research, including measuring microtubule dynamics in Parkinson's disease and drug delivery to the brain. Investigational drugs discussed include NNI-251 (NeuroNascent Inc), neuregulins including glial growth factor 2 (Acorda Therapeutics Inc), AL-108 (Allon Therapeutics Inc) and EVP-0962 (EnVivo Pharmaceuticals Inc). PMID- 20582867 TI - American Society of Gene & Cell Therapy--13th Annual Meeting. AB - The American Society of Gene & Cell Therapy's 13th Annual Meeting, held in Washington, DC, included topics covering new developments in the field of gene therapy. This conference report highlights selected presentations on adenoviral therapies for the treatment of cancer, HIV immunotherapies and gene/cell therapies for the treatment of genetic disorders. Investigational drugs discussed include the TAG vaccine and INGN-007 (both Gradalis Inc), AdCD40L (Uppsala University), Ad5-SSTR/TK-RGD (University of Alabama at Birmingham), CGTG-102 (Oncos Therapeutics Ltd) and lexgenleucel-T (VIRxSYS Corp). PMID- 20582868 TI - H1N1 Swine Flu: The 2010 Perspective--A New York Academy of Sciences Meeting. AB - The H1N1 Swine Flu: The 2010 Perspective conference, held in New York City, included topics covering new research developments regarding the H1N1 influenza virus. This conference report highlights selected presentations on high-yield reassortant viral production, virus transmission and pathogenesis in ferret and guinea pig models, and the advantages of virus-like particle vaccines. Fatal pathology findings from the 2009 H1N1 strain in New York, and preparedness for and response to the 2009 pandemic, are also discussed. PMID- 20582869 TI - Medichem--BIT Life Sciences' First Annual International Conference. AB - Medichem--BIT Life Sciences' First Annual International Conference, held in Beijing, included topics covering new developments in the field of medicinal chemistry for drug discovery. This conference report highlights selected presentations on research into the basic biology of signaling, ion channels and natural products; tools and techniques in medicinal chemistry; and medicinal chemistry for developing drugs for neurological, neoplastic and inflammatory diseases. Investigational drugs discussed include TTA-A8 (Merck & Co Inc). PMID- 20582870 TI - The 'retro-design' concept for novel kinase inhibitors. AB - Protein kinases are among the most attractive therapeutic targets for a broad range of diseases. This feature review highlights and classifies the main design principles employed to generate active and selective kinase inhibitors. In particular, emphasis is focused on a fragment-based lead-generation approach, which constitutes a novel design method for developing type II kinase inhibitors with distinct binding kinetic attributes. This 'retro-design' strategy relies on a customized fragment library, and contrasts the traditional approach used in the design of type II inhibitors. PMID- 20582871 TI - Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders. AB - Mutations located in the human genes encoding voltage-gated calcium channels are responsible for a variety of diseases referred to as calcium channelopathies, including familial hemiplegic migraine, episodic ataxia type 2, spinocerebellar ataxia type 6, childhood absence epilepsy and autism spectrum disorder, all of which are rare inherited forms of common neurological disorders. The genetic basis of these calcium channelopathies provides a unique opportunity to investigate their underlying mechanisms from the molecular to whole-organism levels. Studies of channelopathies provide insight on the relationships between channel structure and function, and reveal diverse and unexpected physiological roles for the channels. Importantly, these studies may also lead to the identification of drugs for the treatment of genetically acquired channel disorders, as well as to novel therapeutic practices. In this feature review, recent findings regarding neurological calcium channelopathies are discussed. PMID- 20582873 TI - Arimoclomol, a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis. AB - Recent years have seen an explosion of research into increasingly prevalent neurodegenerative diseases. Arimoclomol (BRX-220), being developed by CytRx Corp, is an oral therapeutic candidate for the treatment of amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease. ALS is a fatal, incurable disorder, which can present as sporadic (90 to 95% of cases) or familial (5 to 10% of cases) forms. The etiology of sporadic ALS remains unknown and much of the understanding of ALS pathogenesis has been derived through study of its familial forms; in particular, through study of autosomal dominant mutations in the SOD1 (copper/zinc superoxide dismutase) gene, which cause approximately 20% of familial ALS cases. Under conditions of excessive stress, arimoclomol induces amplification of the cytoprotective heat shock response in order to protect motor neurons from death. Comprehensive in vivo and in vitro studies demonstrated its effect in the prevention of neuronal loss and promotion of motor neuron survival, even after symptom onset. Clinical trials have reported good tolerability and safety. This paper discusses the rationale for arimoclomol use in ALS, the preclinical and clinical evidence collected to date, the likelihood of its promising preclinical results translating to humans, and the relevance of this research for neurodegeneration as a whole. PMID- 20582872 TI - GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease. AB - GSK-1605786 (CCX-282; Traficet-EN), a selective antagonist of the CC chemokine receptor (CCR9), is being developed by GlaxoSmithKline plc under license from ChemoCentryx Inc for the potential treatment of inflammatory bowel disease, including Crohn's disease and celiac disease. CCR9 is a tissue-specific lymphocyte trafficking molecule that selectively attracts both B- and T-cells to the small gut. Inhibition of CCR9 by GSK-1605786 may inhibit B- and T-cell entry to the small gut and ameliorate inflammation while leaving immune function at other anatomical sites unaffected. GSK-1605786 was assessed as a treatment for moderate-to-severe Crohn's disease in the phase II/III PROTECT-1 trial and as a treatment for celiac disease in a phase II trial. Data suggest that GSK-1605786 is efficacious in patients with Crohn's disease with the advantage of being orally bioavailable. PMID- 20582874 TI - The effects of protein ingestion on GH concentrations in visceral obesity. AB - Growth hormone (GH), a hormone originating from the anterior pituitary gland, is an important regulator of metabolism and body composition. Low GH secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass. It has been shown that GH release can be promoted by ingestion of protein, in particular gelatin protein. The question remains; is the GH-promoting effect of gelatin protein also present in a population with blunted GH response, such as visceral obesity? 8 lean women (age: 23+/-3 years, BMI: 21.6+/-2.0 kg/m (2)) and 8 visceral obese women (age: 28+/-7 years, BMI: 33.8+/-5.5 kg/m (2)) were compared with regard to their 5-h GH response after oral ingestion of gelatin protein (0.6 g protein per kg bodyweight), placebo (water), or injection of growth hormone releasing hormone (GHRH) (1 mu/kg body weight), in a randomized crossover design. GH response after placebo, gelatin protein, or GHRH was higher in lean subjects than in visceral obese subjects (p<0.05). Ingestion of gelatin protein increased GH response compared with placebo in both visceral obese (182.1+/-81.6 microg/l.5 h vs. 28.4+/-29.8 microg/l.5 h) and lean (631.7+/-144.2 microg/l.5 h vs. 241.0+/-196.8 microg/l.5 h) subjects (p<0.05). GH response after ingestion of gelatin protein in visceral obese did not differ from that in lean, placebo-treated subjects (p=0.45). GH concentrations after GHRH injection correlated significantly with GH concentrations after gelatin ingestion (AUC; r=0.71, p<0.01, Peak; r=0.81, p<0.01). Further research is needed to investigate if gelatin protein is able to improve metabolic abnormalities in hyposomatotropism in the long term or to investigate the relevance of protein as diagnostic tool in hyposomatotropism. PMID- 20582875 TI - [Preoperative smoking cessation in patients with lung cancer]. AB - Successful smoking cessation is associated with a survival benefit for patients with lung cancer. However, smokers newly diagnosed with non-small cell lung cancer and scheduled for curative resection are frequently discouraged from stopping smoking in the immediate preoperative period. This recommendation is based on the results of one single prospective cohort study published in 1998 which reported an increased risk of perioperative pulmonary complications in patients undergoing non-thoracic surgery who had reduced their tobacco consumption within the two months leading up to the operation. During the past 12 years, numerous observational studies have investigated the impact of preoperative smoking cessation on perioperative risk for thoracic and non thoracic surgery. However, no more than six studies included patients with pulmonary neoplasms. Owing to methodological limitations and considerable heterogeneity of the included patient groups, the existing data are insufficient to support or refuse any recommendation regarding cessation advice for patients during the immediate preoperative phase. In view of the post-cessation recovery time-course of pathophysiological alterations relevant to the occurrence of perioperative complications, a smoke-free preoperative interval of 2 - 6 weeks appears most favourable. However, this is difficult to achieve as a curative resection should not be postponed. Since there is no scientific evidence demonstrating a negative impact of preoperative smoking cessation on prognosis, patients newly diagnosed with lung cancer should be encouraged to make an attempt to quit while waiting for thoracic surgery. PMID- 20582876 TI - Acute effects of delta9-tetrahydrocannabinol on the auditory evoked mismatch negativity are modulated by the NRG1 gene. PMID- 20582877 TI - [Conserving surgery for breast cancer]. AB - Breast cancer is the first women's cancer. Conserving surgery associated with radiotherapy, is in progress. Her indications are frequent. The result for local control and global survival are the same as radical surgery. PMID- 20582878 TI - Helicobacter pylori and gastric cancer. AB - BACKGROUND: Patients infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies, in particular gastric carcinomas. AIM: This review was aimed to analyze the relationship between gastric carcinoma and Helicobacter pylori infection and to rule out the possibility of preventive measures. METHODS: To identify articles for this review, a PubMed search was conducted using the following key words: gastric cancer, Helicobacter pylori. RESULTS: The risk for developing cancer includes environmental, host-genetic and bacterial factors, which induce physiologic and histologic changes in the stomach. There are two major pathways for the development of gastric cancer by helicobacter pylori: the indirect action on gastric epithelial cells through inflammation leading to gastric atrophy and intestinal metaplasia and the direct action through the induction of protein modulation and gene mutation. PMID- 20582879 TI - [Biliary stent occlusion]. AB - BACKGROUND: Endoscopic stent insertion is as a method of choice for palliative treatment of malignant biliary strictures. Two types of biliary stent were actually used plastic and metallic self-expandable. Occlusion of the stent can be observed in both. AIM: To assess the management of biliary stent occlusion. METHODS: From january 2006 to december 2007, 120 biliary stents were inserted in 97 patients. Indications of biliary stents were malignant stricture in 67% of cases. Biliary stent occlusion was defined by necessity of stent replacement. RESULTS: 118 plastic and 2 metallic self-expandable biliary stents were inserted. Obstruction of the biliary stent was observed in 12 patients, after a mean time of 5,5 months [1-15]. A recurrent biliary desobstruction was necessary in 6 patients. Stent exchange was realised in 33,3% of cases for malignant biliary stenosis and in 66,6% for benign stricture (p=0,01). Obstruction of the stent was symptomatic (cholangitis, jaundice) in more of 50% of cases. Management consisted on the stent exchange by a new plastic stent for clogging plastic stent and on insertion of plastic stent inside the metallic one for the occluded metallic stent. CONCLUSION: Obstruction can occur for the two types of biliary stent. Survival of the patient, cost of the stent guide the choice of the stent will be used. PMID- 20582880 TI - C-telopeptides of type I collagen in postmenopausal women: an experience in a Tunisian clinical laboratory. AB - AIM: The purpose of study was to evaluate the interest of C-telopeptides of type I collagen (CTX) in the diagnosis of osteoporosis in postmenopausal women and to define its cut-off value. METHODS: A transverse descriptive study enrolled postmenopausal women: 139 osteoporotic (G1) and 39 non osteoporotic (G2). The 2 groups were defined by bone density measurement. The following markers were measured: serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX). Statistical analyses were performed using SPSS 10.5. The corresponding estimation of sensitivity and specificity of CTX have been presented as 'receiver Operating Curve' (ROC). RESULTS: There was no difference in the measurement of ALP and bone ALP in the 2 groups but CTX was statistically higher in G1 compared to G2 (p <0.001). The percentage of osteoporotic women (G1) with CTX values > 0.500 ng/ml was higher than that of non osteoporotic women (G2). We have established a ROC curve to find the cut-off value of CTX that enables the distinction between osteoporotic women with high level of bone remodelling, and non osteoporotic women. The cut-off value of CTX 0.55 pg/ml was the best; it associated best sensitivity and specificity. CONCLUSION: The total increase and significance for CTX was greater in the group of osteoporotic women and appeared therefore to be a good bone turnover marker in the diagnosis of osteoporosis in comparison with ALP and bone ALP. The cut-off value of CTX 0.55 pg/ml may improve the sensitivity and specificity of prediction of future fractures. PMID- 20582881 TI - Comparison of cigarette and waterpipe smoking among pupils in the urban area of Sousse, Tunisia. AB - BACKGROUND: Epidemiological and observational evidence suggests that waterpipe use is growing in popularity worldwide. AIM: The purpose of this study was to examine the prevalence of cigarette and water pipe tobacco use among pupils aged 13-17 years in the urban area of Sousse, Tunisia and to identify the factors which predict current cigarette and/or waterpipe smoking in this population. METHODS: Across-sectional study was carried out on a representative sample of schoolchildren aged between 13 and 17 years in colleges and public secondary schools of the urban area of Sousse. We used a pre tested and self administered questionnaire to measure tobacco consumption. The significance level for all analyses was p<0.05. Statistical analysis was conducted with SPSS 10.0 software. RESULTS: Participants were 1569 youth. Fifty two percent of them were male. The mean age of the sample was 15+/-1.5 years. Total cigarette smoking percentage for ever and current use were 33.1% and 7.6% respectively. Total water pipe smoking percentage for ever and current use were 19.3% and 5.2% respectively. Overall, the total percentages of cigarette and water pipe smoking (ever and current) were higher for male and aged pupils. Multivariate regression analyses showed that the two types of tobacco use were related. CONCLUSION: Despite the growing adoption of water-pipe smoking, there remains limited research in this area. Increased surveillance and additional research are necessary to address this growing threat to public health. PMID- 20582882 TI - Childhood nephrectomy indications: a changing profile. AB - AIM: To assess the changing profile of children's nephrectomy indications in the south of Tunisia during the last two decades. METHODS: There were 94 children who underwent nephrectomy between 1982 and 2007. They were classified into two groups. The first group included 55 out of 511 hospitalized children between 1982 and 1994, the second included 39 out of 382 hospitalized children between 1995 and 2007. K2 (Chi-squared) test was used for this statistical analysis. A P value of < 0.05 was considered statistically significant. RESULTS: The average was 7. Pathologies leading to nephrectomies were dominated in both groups by 3 main aetiologies: urolithiasis (42.5%), Wilm's tumors (21.3%) and pelvi-ureteric junction (13.8%). While in the first group, urolithiasis was found to be the major indication of nephrectomy (54.5%, p<0.05), in the second group, kidney tumors had become the major indication (33%, p<0.05) followed by urolithiasis (25.6%). So, the rate of nephrectomies performed due to urolithiasis had clearly decrease (P = 0.005), but there were no statistical differences observed between the rates of nephrectomies performed due to tumors or upper urinary tract malformations in the two groups. CONCLUSION: The profile of children's nephrectomy indications in Tunisia stretches currently to be similar to the one of the industrialized countries, with regression of evolved kidney lithiasis leaving place to the tumorous pathologies, because of early detection, improvement and appropriate treatment of urinary lithiasis. PMID- 20582883 TI - [Adjuvant chemotherapy in resected non small cell lung cancer: preliminary results about 8 cases]. AB - AIM: Report the preliminary results of adjuvant chemotherapy in patients surgically treated for non small lung cancer. METHODS: It's a prospective study about 12 patients surgically treated between January 2005 and December 2007.8 patients had benefit of adjuvant chemotherapy. The protocol had been based at 4 cycles of Cisplatine. RESULTS: Our 8 men patients, aged for the mean of 59 years with a Performans Status at 1, had benefit of adjuvant chemotherapy after curative surgery. Six patients considered us II B stage, had benefit immediately for surgically treatment. Adjuvant chemotherapy protocol had been based of Cisplatin and Vinorelbine (5 patients) and Cisplatin and Gemcitabine (1 patient). The 4 cycles can be administered without any limiting toxicity only for one patient who's received 2 cycles of Cisplatin and Gemcitabine in front of the severity of digestive side effects. Two patients considered us IIIB stage, had been surgically treated after neo adjuvant chemotherapy based at Cisplatin and Vinorelbine. Histological response was complete for twice of them. The same chemotherapy was stopped after 2 cycles us adjuvant, in front of haematological side effects. Two patients did at 4 and 15 months of neoplasic progression. The six other patients had been still on life with a move back of 33 months. CONCLUSION: Post operative adjuvant chemotherapy is the standard treatment for the II A and II B stages and probably for IB stage. For none immediately operative patients (IIIA and some III B), articulation of chemotherapy with surgery must be clarified. PMID- 20582884 TI - [Neonatal hearing screening with transient otoacoustic emissions: pilot study]. AB - BACKGROUND: Bilateral hearing loss is present in 1-3 per 1000 newborn infants, and in 2-4 per 100 infants in the intensive care unit population. All infants with hearing loss should be identified before 3 months of age and receives intervention by 6 months. If undetected, this will impede speech, language, and cognitive development. In Tunisia, we do not have an exhaustive information on the real importance of the auditive handicap. The aim of our study was to evaluate the feasibility and the practical aspects of a pilot tunisian universal neonatal hearing screening (UNHS) program based on transient evoked otoacoustic emission reporting the incidence of hearing impairment in this population. METHODS: A prospective study during one year (01/05/2006 to the 30/04/2007). Transient evoked otoacoustic emission was planned for all live births. If the test could not be practised in maternity or that research was negative, an appointment was delivered for a research of the O.T.E.A.P in an interval of 1 week - 1 month. Infants who did not meet TEOAE pass criteria underwent diagnostic auditory brainstem response (ABR) testing. RESULTS: During the study period, 3342 live births were recorded, 3260 were included. Total coverage rate was of 41% (1333/3260). We recorded 3 cases of bilateral hearing loss (0.9 per thousand screened infants) and 5 with unilateral sensorineural hearing loss (1.5 per thousand screened infants). CONCLUSION: The incidence of congenital hearing loss in our population seems relatively high. Hearing screening for all neonates using transient evoked otoacoustic emission is feasible but several practical aspects should be revised. PMID- 20582885 TI - [Sirolimus-eluting stent in the prevention of restenosis in small coronary arteries]. AB - BACKGROUND: Angioplasty of coronary arteries with a small diameter (commonly defined as diameter inferior than 2.75 mm) is associated with a high rate of restenosis and revascularization. Since the use of Drug Eluting Stents (DES) and considering their good results on simple lesions compared to other techniques (balloon dilation and bare metal stents), many studies have also demonstrated the superiority of DES in reducing restenosis and revascularization of complex lesions in particular lesions on coronary arteries with small diameter. AIM: Assessment of this revascularization procedure. METHODS: Our study is a prospective one carried on between june 2002 and august 2006, involving a cohort of 299 patients. Patients are divided into 2 groups: group I: 175 patients with 220 lesions on coronary arteries with small diameter treated by 233 sirolimus DES (Cypher) and group II: 124 patients treated by 136 angioplasty of coronary arteries with diameter superior than 2.75 mm using 179 DES. RESULTS: During hospitalisation, there was no significant difference in MACE between the 2 groups. Nevertheless, 2 patients among the first group had no angioplasty because of unsuccessful progression of the balloon through the lesion and the absence of atherectomy in our center. All patients having acute thrombosis during hospitalization and presenting with ST elevated acute coronary syndrome had successful urgent revascularization with TIMI 3 flow. The mid-term follow-up (12 months) concerned 157/174 patients in group I and 113/123 patients in group II. We observed a higher mortality and non fatal myocardial infarction in group I without statistically significant difference. CONCLUSION: despite the complexity of the lesions on coronary arteries with small diameter and despite the association with several risk factors in particular diabetes, the use of DES reduces the MACE specially secondary revascularisations thus improving early and midterm prognosis. PMID- 20582886 TI - [Pulse-wave Doppler Tissue Imaging in the assessment of regional left ventricular diastolic function in patients with coronary artery disease]. AB - AIM: Myocardial ischemia impairs the diastolic left ventricular (LV) function earlier than the systolic function. We evaluated the value of pulse-wave Doppler Tissue Imaging (DTI) in the study of regional myocardial function of LV in patients with coronary artery disease. METHODS: We performed a prospective study in 60 patients with coronary artery disease that we compared to 40 healthy individuals in order to assess the value of pulse-wave DTI to study the diastolic LV function . Both groups had a clinical examination, ECG, echocardiography and pulse-wave DTI. Only the patients had a coronary angiography. Pulse-wave DTI was applied to the 16 myocardial segments of the LV, we measured the isovolumetric relaxation time (IVRT), early (Ea) and late diastolic (Aa) velocities. RESULTS: We have demonstrated that compared with healthy subjects, patients with coronary artery disease has a significant increase of IVRT (100.2 +/- 20 ms vs 62.5 +/- 12.2, p <0.001) and lower Ea (7.6 +/- 1.6 vs. 9.2 +/- 2.6) and report Ea / Aa. These anomalies are more pronounced in akinetic segments compared with hypokinetic segments. Relying on data from the coronary angiography, we found in patients that IVRT had increased, Ea and Ea / Aa lowered in most segments hypoperfused than in normally perfused segments. An IVRT > 70ms and Ea <8.3 cm / s emerge as threshold values to identify myocardial ischemia. More coronary lesions are severe more Ea and Ea/Aa decline and IVRT increase. The culprit coronary artery could be identified by pulse- wave DTI since the DTI parameter anomalies are systemized CONCLUSION: The pulsed DTI technique seems to be attractive as a non-invasive evaluation method of ischemic heart disease. PMID- 20582887 TI - [HELLP syndrome: about 17 cases and literature review]. AB - BACKGROUND: HELLP syndrome is defined as an association of hemolytic anemia, raised liver enzymes and thrombocytopenia. It is a severe manifestation of pre eclampsia. AIM: We tried to specify the epidemic factors and the best management of HELLP syndrome Methods: A retrospective study held during 6 years in the department of gynaecology and obstetrics in La Marsa hospital and according to a literature revue. RESULTS: The dominating symptoms included low abdominal pain and vomiting. The syndrome was discovered after 30.5 weeks of amenorrhea on average. Infant extraction was by cesarean section in 11 cases. Maternal morbidity was mainly marked by eclampsia and haemostatic disturbances while neonatal morbidity was attributable to the included prematurity. CONCLUSION: The main management consists essentially in a medical reanimation, in addition to a rapid foetal extraction. PMID- 20582888 TI - [Investigation of three nosocomial outbreaks of Serratia marcescens in an intensive care unit in Sfax-Tunisia]. AB - THE AIM of the study was to type Serratia marcescens responsible for nosocomial outbreaks in an intensive care unit in Sfax -Tunisia. METHODS: The relatedness between S. marcescens isolates was studied by Pulsed field gel electrophoresis (PFGE). We included 56 strains of Serratia marcescens isolated from patients hospitalized in the intensive care unit during 2003 and 2004. Seven epidemiological unrelated strains of Serratia marcescens were also tested. Samples from environment and hands of the nursing and medical staff were collected and cultured to identify the source of contamination. RESULTS: All strains showed a wild type of antimicrobial susceptibility. PFGE typing revealed that three different clones were present. None of the cultures taken from hands of unit staff and from environmental samples yielded positive results for S. marcescens. CONCLUSION: We have confirmed the presence of three consecutive outbreaks caused by three genetically unrelated bacterial clones of Serratia marcescens in the intensive care unit ward. These outbreaks are closely related to the frequent use of colistin and the lack of measures of hygiene in this ward. PMID- 20582889 TI - [Immature teratoma of the ovary and pregnancy]. AB - BACKGROUND: Composing of less than 1% of all ovarian cancers, immature teratoma is a malignancy that mainly affects the young. Immature teratoma of the ovary together with pregnancy is rare. To our knowledge, this association was reported only in twelve cases. AIM: We Report two cases of immature teratoma of the ovary diagnosed during pregnancy and their respective issue. OBSERVATION: 1st case. A 28 years old woman gravida 1 with an immature teratoma of the ovary discovered during delivery by caesarean section. The treatment was conservative including salpingo-oophorectomy, omentectomy, aortic lymph node dissection and appendectomy. This patient had a second pregnancy with a good outcome. She delivered by caesarean section in order to perform radical treatment: hysterectomy and oophorectomy of the remaining ovary. 2nd case. A 22 years old woman gravida 1 with adnexal mass diagnosed during an ultrasonography exam at 15 weeks gestation. A conservative treatment was indicated, including salpingo oophorectomy, omentectomy, aortic lymph node dissection, appendectomy and biopsy of the remaining ovary. The patient had a normal vaginal delivery. CONCLUSION: Immature teratoma is graded from 1 to 3. The management of this association is discussed, but it takes in consideration the surgical staging, the grade and the secretion of aFP. Conservative treatment without associating chemotherapy can be tempted in tumours with a stade AI and a low grade. PMID- 20582890 TI - Transitory, spontaneously recovering, peripheral facial nerve palsy after vionorelbine administration. AB - BACKGROUND: Vinorelbine is a semi-synthetic vinca alkaloid that has demonstrated a broad spectrum of activity. It is widely used in non small cell lung cancer. CASE REPORT: We report the case of a 50 year old man, having stage IV lung carcinoma with a unique cerebral metastasis in the right hemisphere. Focal cerebral radiotherapy was first administrated followed by intravenous chemotherapy associating vinorelbine to cisplatin. He has developed multiple subsequent and transitory episodes of monolateral peripheral facial nerve palsy in the left side during vinorelbine administration. The palsy has completely and spontaneously resolved at a short interval, around twenty minutes, after the end of the drug infusion. Obvious cerebral tumor progression was excluded by means of CT scan; the drug was thereby administrated as scheduled until the end of the treatment. CONCLUSION: We describe an unusual side effect, until now reported in only two cases, having brain-stem gliomas, among English and French literature, dealing with vinorelbine as adjuvant treatment. We discuss possible neurological and oncological implications. PMID- 20582891 TI - Childhood occipital epilepsy of Gastaut: a case report. AB - BACKGROUND: Idiopathic childhood occipital epilepsy of Gastaut is a rare but well defined syndrome within the group of idiopathic focal epilepsies in childhood. Clinical manifestations are characterized by simple partial seizures with mainly visual symptoms followed by secondary generalization. AIM: Report of a case of Childhood Occipital Epilepsy. CASE REPORT: We report a case of 10-year-old-girl, with no history. At the age of 9 years, the patient started experiencing repetitive events without fever. The first event consisted of several episodes of loss of consciousness with hypotonia and post ictal amnesia. The second type was three episodes of stereotyped, elaborated complex visual hallucinations, during 10 minutes. One month later, a third type of tonico-clonic generalized seizures appeared. Neurological examination and routine laboratory investigation were normal. Brain neuroimaging was normal. Interictal EEG showed bilateral discharges of slow generalized waves activated by hyperventilation. She has been treated by Sodium Valproate. All seizures stopped and she remained free of seizures. CONCLUSION: This epileptic syndrome must be identified, and treated without delay. In fact, without appropriate treatment, the evolution may lead to a continuous spike-wave during the sleep with cognitive deterioration. PMID- 20582892 TI - Cutaneous, pulmonary and sinusal aspergillosis in a diabetic patient. AB - BACKGROUND: Cutaneous aspergillosis is rarely reported in diabetic patients. AIM: The objective of our study is to report a case of lethal disseminated aspergillosis revealed by multiples skin necroses, with pulmonary and sinusal involvement in a diabetic patient. CASE REPORT: A 60-year-old diabetic woman, presented with one month -rapidly -extensive, 1 to 10 cm skin necroses of the trunk, limbs and eyelids. Few days after her admission, she developed dyspnoea. Chest X-ray showed an interstitial and alveolar syndrome with multiple excavated anfractuous-edged-opacities. Facial CT scan showed a right orbital cellulitis with Pansinusitis. The methaminesilver stains on a cutaneous biopsy showed filamentous septate fungal hyphae with branches at right angles. The immunofluorescence with an anti-aspergillus serum was positive. The diagnosis of secondary disseminated aspergillosis to a primary pulmonary focus with cutaneous, sinusal, and upper airway's dissemination was made. The patient died despite an intravenous amphotericin B therapy. CONCLUSION: This report emphasizes the importance of evoking and seeking for a mycosis in every skin necrotic and ulcerative lesions occurring in an immunocompromised patient. The prognosis depends on the diagnosis and treatment institution delay. PMID- 20582893 TI - [Primitive adenocarcinoma of the fallopian tube]. PMID- 20582894 TI - [Prenatal diagnosis of left atrium congenital diverticula]. PMID- 20582895 TI - [Placenta accreta]. PMID- 20582896 TI - [Cardiogenic and non cardiogenic pulmonary edema: pathomechanisms and causes]. AB - The development of pulmonary edema is divided in cardiogenic and non-cardiogenic. Cardiogenic edema pathogenically is caused by elevated hydrostatic pressure in the pulmonary capillaries due to left sided congestive heart failure. Non cardiogenic pulmonary edema is categorized depending on the underlying pathogenesis in low-alveolar pressure, elevated permeability or neurogenic edema. Some important examples of causes are upper airway obstruction like in laryngeal paralysis or strangulation for low alveolar pressure, leptospirosis and ARDS for elevated permeability, and epilepsy, brain trauma and electrocution for neurogenic edema. The differentiation between cardiogenic versus non-cardiogenic genesis is not always straightforward, but most relevant, because treatment markedly differs between the two. Of further importance is the identification of the specific underlying cause in non-cardiogenic edema, not only for therapeutic but particularly for prognostic reasons. Depending on the cause the prognosis ranges from very poor to good chance of complete recovery. PMID- 20582897 TI - [Prevalence of heart murmurs, aortic and pulmonic stenosis in boxers presented for pre-breeding exams in Switzerland]. AB - Boxer are predisposed to subaortic (SAS) and pulmonic stenosis (PS). To decrease the prevalence, pre-breeding cardiologic exams were performed in the last years. In our study the results of 309 pre-breeding exams of boxers presented between 1999 and 2008 were evaluated retrospectively. The overall prevalence of heart murmurs was 26.5 %. A SAS was diagnosed in 25 (8.1 %) and a PS in 10 (3.3 %) dogs. A combination of both defects was found in 7 (2.3 %) Boxers. Animals with a heart murmur of at least grade 3/6 had a significantly higher peak aortic flow velocity (VmaxAo) than animals without or only soft heart murmurs. Over the study period both the frequency of heart murmurs and diagnosis of SAS and PS decreased. PMID- 20582898 TI - [Left ventricular hypertrophy in the cat - "when hypertrophic cardiomyopathy is not hypertrophic cardiomyopathy"]. AB - According to WHO classification hypertrophic cardiomyopathy (HCM) is a primary genetic cardiomyopathy. Echocardiographically HCM is characterized by symmetric, asymmetric or focal left ventricular hypertrophy (LVH) without recognizable underlying physical cause. However, echocardiographically HCM in cats may not be distinguishable from other causes of a thick appearing left ventricle. Hypovolemia can look like a hypertrophied ventricle but is basically only pseudohypertrophic. Well recognized and logical physical causes of LVH include systemic hypertension and outflow obstruction. LVH similar to HCM may also be found in feline hyperthyroidism. The context of the disease helps to differentiate these physical / physiological causes of LVH. Difficult to distinguish from HCM, particularly when based on a snapshot of a single echocardiographic exam, are myocarditis and <>. Only the clinical and echocardiographic course allow a reasonably confident etiological diagnosis and the differentiation between HCM and secondary LVH. PMID- 20582899 TI - [Natural infection with Angiostrongylus vasorum: characterisation of 3 dogs with pulmonary hypertension]. AB - Pulmonary hypertension (PH), together with its accompanying clinical signs and underlying causes, e.g. pulmonary thrombosis, are more and more recognized as an important clinical entity also in dogs. This article characterizes the clinical picture of 3 dogs with PH caused by natural infection with Angiostrongylus vasorum. All 3 dogs were of small breeds ( < 10 kg), the age at the time of diagnosis was 1, 2 and 11 years. Clinically, dyspnea and exercise intolerance were the predominating signs, 2 dogs developed hemoptysis, 1 dog developed right sided congestive heart failure. Severe arterial hypoxemia (PaO2 41 - 53 mmHg) reflected the severity of pulmonary parenchymal and vascular damage. Severe hyperglobulinemia (59 und 88 g/l) in two dogs implicated a long lasting infection. Anthelmintic treatment in 2 dogs resulted in quick clinical, radiographic and echocardiographic normalization. PH is the consequence of multiple causes and pathomechanisms, and the recognition of PH is primarily of differential diagnostic relevance. Prognosis and therapy in cases with PH mainly depend on the underlying cause, rather than on the PH and on its degree. PMID- 20582900 TI - [20 years since the control of transmitted eye diseases]. PMID- 20582904 TI - Abstracts of the XII Symposium on Vascular Access For Hemodialysis. Las Vegas, Nevada, USA. May 12-14, 2010. PMID- 20582903 TI - Abstracts of the International Congress Angio Access for Hemodialysis. Tours, France. June 14-16, 2010. PMID- 20582905 TI - Analgesic use and the risk for progression of chronic kidney disease. AB - PURPOSE: The chronic effect of various analgesics on the progression of chronic kidney disease (CKD) is inconclusive. There is also lack of information on the renal safety of selective cyclooxygenase-2 (COX-2) inhibitors. This study aimed to clarify the renal risk of analgesic use in CKD patients. METHODS: A cohort study using a nationally representative database randomly sampled from National Health Insurance (NHI) enrollees was performed. The study population included a total of 19,163 newly diagnosed CKD patients. Clinical conditions were defined by diagnostic codes and exposure information on analgesics was derived from service claims. Cox proportional hazard model was used to assess the association between analgesic use and the risk of progression to end stage renal disease (ESRD). RESULTS: CKD patients using acetaminophen, aspirin, and non-selective non steroidal anti-inflammatory drugs (NSAIDs) had an increased risk for ESRD with multivariable-adjusted HRs (95%CIs) of 2.92 (2.47-3.45), 1.96 (1.62-2.36), and 1.56 (1.32-1.85), respectively. The trends toward higher risk with increasing exposure dose were significant for all classes of analgesics (all P for trend < 0.001). Among COX-2 inhibitors, only rofecoxib, but not celecoxib, shows a significant risk association with ESRD (HR = 1.98; 95%CI, 1.15-3.40). CONCLUSIONS: Our data indicated exacerbating effects of acetaminophen, aspirin, and non-selective NSAIDs on CKD in a dose-dependent manner. For COX-2 inhibitors, only rofecoxib showed an increased risk for ESRD. Although the possibility of residual confounding cannot be completely ruled out, given the common use of analgesics, the possible relation suggested by this study warrants further investigation. PMID- 20582906 TI - Ginkgo biloba and risk of cancer: secondary analysis of the Ginkgo Evaluation of Memory (GEM) Study. AB - PURPOSE: Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date. METHODS: A total of 3069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120 mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo. RESULTS: During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio (HR), 1.09; 95% confidence interval (CI), 0.87-1.36; p = 0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95%CI, 0.97-4.80; p = 0.06) and colorectal (HR, 1.62; 95%CI, 0.92-2.87; p = 0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95%CI, 0.43-1.17; p = 0.18). CONCLUSIONS: Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer. PMID- 20582907 TI - Pharmacoepidemiology of patients hospitalized for somatoform disorders in psychiatric hospitals and departments. AB - PURPOSE: Pharmacological treatment is used in patients with somatoform disorders (SD) although the empirical evidence is scarce. We evaluated the current pharmacological treatment strategies used for psychiatric in-patients diagnosed with SD in Central Europe. METHODS: Cross-sectional data of the pharmacological treatment, age, gender, and the primary psychiatric diagnosis of 70,566 in patients were collected on 2 days in April and October of the years 1994-2006 in 57 psychiatric hospitals and departments. RESULTS: Three hundred fifty nine patients corresponding to 0.51% of the psychiatric in-patient population were hospitalized for SD. 94.7% of the SD patients received psychopharmacological treatment including antidepressants (78.2%), neuroleptics (43.3%), tranquilizers (22.6%), hypnotics (15.6%), and anticonvulsants (12.3%). 61.3% were treated with psychotropic combinations, most commonly antidepressant and neuroleptic (36.2%). In addition, 63.7% received one or multiple somatic medications. DISCUSSION: As compared to general medical and neurological in-patient populations, SD patients represent a small proportion of the psychiatric in-patient population. They commonly receive multiple psychotropic and somatic medications. The psychotropics used have predominantly sedating characteristics. CONCLUSION: SD patients are at risk of polypharmacy in psychiatry. PMID- 20582908 TI - Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database. AB - PURPOSE: Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulation. This study investigated the risk of ICH for phenprocoumon which is the most widely used oral anticoagulant in Germany. METHODS: We conducted a nested case-control study in a cohort of 13.4 million insurants of 4 German statutory health insurances (SHIs) who were continuously enrolled for 6 months prior to cohort entry. Cases were patients hospitalized for ICH. Ten controls were matched to each case by SHI, birth year, and sex using incidence density sampling. Rate ratios (RR) of ICH for current phenprocoumon use as compared to non-use were estimated from odds ratios calculated by conditional logistic regression analyses considering multiple risk factors. RESULTS: Analysis of the full cohort revealed a strong increase in incidence of ICH with increasing age. In the nested case-control study including 8138 cases of ICH and 81,373 matched controls, we observed an increased risk of ICH for current phenprocoumon exposure that varied with age. The phenprocoumon-associated risk of ICH was lower in older age groups with RRs from 4.20 (95% confidence interval (CI) 2.44-7.21) for phenprocoumon users less than 55 years of age to 2.43 (95%CI, 1.81-3.27) for those older than 85 years. Our study confirmed known risk factors of ICH. DISCUSSION: Phenprocoumon exposure was associated with an increased risk of ICH. The interaction of risk for phenprocoumon with age was unexpected and needs further study. PMID- 20582909 TI - Prescribing of anti-osteoporotic therapies following the use of proton pump inhibitors in general practice. AB - PURPOSE: To determine the association, if any, between the prescribing of proton pump inhibitors and drugs for the management of osteoporosis. METHODS: The study employed a retrospective cohort design using the Irish Health Services Executive (HSE) Primary Care Reimbursement Services (PCRS) pharmacy database, which contains prescription information for 1.2 million people (30% of the population). Those aged 55 years and over were included. Individuals were classified as new PPI users if they initiated PPI therapy after 2003, and those not receiving PPI therapy after 2003 as the comparison group. Subsequent prescribing of anti osteoporotic therapy was considered from 2004 to 2007 in both groups. Adjusted odds ratios (OR and 95%CIs) were determined by logistic regression, adjusting for age, gender and medications, which potentially affect bone mineral density. RESULTS: 442,341 patients were identified, 209 175 were PPI users and the 233,166 were used as the comparison group. The odds ratio (95%CI) for the prescribing of anti-osteoporotic therapies following the prescribing of PPIs was OR = 1.69 (95%CI 1.66 1.72) compared to not receiving any PPI therapy, when adjusted for age and sex. When adjustments were made for other confounders, the OR decreased to OR = 1.26 (95%CI 1.23-1.28). The strength of the association increased with increasing duration of PPI therapy 6-12 months OR = 1.19 (95%CI 1.15-1.23) and for >24 months, OR= 2.09 (95%CI 2.04, 2.13) compared to < 3 months. The OR also increased with increase in dose of therapy. CONCLUSION: The results of the study indicate the association between the prescribing of bisphosphonates following the use of proton pump inhibitors may be clinically relevant. PMID- 20582910 TI - Statin and NSAID use and prostate cancer risk. AB - PURPOSE: Some studies have reported reduced risks of advanced, but not early, prostate cancer among statin users, and one study found a reduced risk only among statin users who had also used non-steroidal anti-inflammatory drugs (NSAIDs). We have previously reported no association between statin use and prostate cancer in our hospital-based Case Control Surveillance Study. The purpose of the present analyses was to update the findings by cancer stage and to evaluate the joint use of statins and NSAIDs. METHODS: Cases were 1367 men with prostate cancer and controls were 2007 men with diagnoses unrelated to statin or NSAID use. We used multivariable logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for statin use compared with no use, and joint use of statin and NSAIDs compared with use of neither. RESULTS: The odds ratio among regular statin users was 1.1 (95%CI 0.9-1.5), and odds ratios were similar among early and late stage cancers. The odds ratio among joint statin and NSAID users was 1.1 (95%CI 0.7-1.6). CONCLUSION: The present results do not support a protective effect of statin use, or statin and NSAID use, on the risk of advanced prostate cancer. PMID- 20582911 TI - Increased risk of hospitalization for acute hepatitis in patients with previous exposure to NSAIDs. AB - BACKGROUND: Epidemiological studies related to hospitalization due to the hepatotoxicity of traditional non-steroidal anti-inflammatory drugs (NSAIDs) are infrequent, and case reports of hepatotoxicity of nimesulide, celecoxib, and rofecoxib seem to be increasing. The reimbursement database of National Health Insurance (NHI) in Taiwan provided an opportunity for post-marketing surveillance. We conducted this study to determine the association between the use of hepatoxic NSAIDs and increased hospitalizations related to acute hepatitis. METHODS: We included hospitalized subjects with a major diagnosis of acute or sub-acute necrosis of liver or toxic hepatitis and excluded viral and other causes of hepatobiliary diseases from the NHI database from 1 April 2001 to 31 December 2004. We applied two kinds of models to analyze by uni-directional and bi-directional case-crossover designs during the 28 days exposure periods and performed conditional logistic regression models. RESULTS: There were 4519 cases of hospitalization relating to acute hepatitis, and the odds ratios of celecoxib, nimesulide, dicofenac, ibuprofen, and other hepatoxic NSAIDs were significantly increased. Compared with the adjusted odds ratios of other hepatoxic NSAIDs (OR = 2.13, 95%CI = 2.00, 2.28), celecoxib (OR =1.92, 95%CI = 1.38, 2.69) was similar during the 28 days by our uni-directional case-crossover design. CONCLUSIONS: Our results provide evidence for an increased risk of hospitalization with acute hepatitis among hepatoxic NSAIDs including celecoxib users. Further mechanistic research is warranted in order to document celecoxib's hepatotoxicity. PMID- 20582912 TI - Factors associated with the use of corticosteroids in the initial management of idiopathic pulmonary fibrosis. AB - PURPOSE: Idiopathic pulmonary fibrosis (IPF) has not been shown to respond to corticosteroid therapy; however, many patients receive these drugs at the time of diagnosis. The factors that are associated with the decision to prescribe corticosteroids have not been examined. METHODS: We conducted a retrospective cohort study of 1126 patients with a new diagnosis of IPF using The Health Improvement Network (THIN) database from the United Kingdom. We used generalized estimating equation (GEE) regression models to test the association of patient characteristics, co-morbid diseases, and disease characteristics with the use of corticosteroids within 30 days of IPF diagnosis. RESULTS: Bivariable analyses demonstrated an association between female sex, the presence of dyspnea, the need for oxygen, past steroid use, and the use of corticosteroids immediately prior to diagnosis with the use of corticosteroids at the time of diagnosis. After adjustment with multivariable GEE regression, only the use of oxygen at the time of diagnosis (OR 1.69, CI 1.14-2.49), the past use of corticosteroids (OR 1.50, CI 1.04-2.15), and use of corticosteroids immediately prior to diagnosis (OR 5.72, CI 3.80-8.60) remained significantly associated with the use of corticosteroids immediately following diagnosis. No association was found between prior diabetes, osteoporosis, glaucoma, hypertension, congestive heart failure, obesity, or peptic ulcer disease and use of corticosteroids at diagnosis. CONCLUSIONS: The decision to prescribe corticosteroids is associated with oxygen use and past corticosteroid use but is not influenced by factors such as age, gender, or common co-morbid conditions that may pre-dispose patients to adverse events of therapy. PMID- 20582913 TI - Improved antimicrobial activity of h-lysozyme (107-115) by rational Ala substitution. AB - The most challenging target in the design of new antimicrobial agents is the development of antibiotic resistance. Antimicrobial peptides are good candidates as lead compounds for the development of novel anti-infective drugs. Here we propose the sequential substitution of each Ala residue present in a lead peptide with known antimicrobial activity by specific amino acids, rationally chosen, that could enhance the activity of the resultant peptide. Taking the fragment 107 115 of the human lysozyme as lead, two-round screening by sequentially replacing both Ala residues (108 and 111) by distinct amino acids resulted in a novel peptide with 4- and 20-fold increased antimicrobial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, respectively. These results reinforce the strategy proposed, which, in combination with simple and easy screening tools, will contribute to the rapid development of new therapeutic peptides required by the market. PMID- 20582914 TI - Informed consent for genetic research. AB - Genetic research often utilizes or generates information that is potentially sensitive to individuals, families, or communities. For these reasons, genetic research may warrant additional scrutiny from investigators and governmental regulators, compared to other types of biomedical research. The informed consent process should address the range of social and psychological issues that may arise in genetic research. This paper addresses a number of these issues, including recruitment of participants, disclosure of results, psychological impact of results, insurance and employment discrimination, community engagement, consent for tissue banking, and intellectual property issues. Points of consideration are offered to assist in the development of protocols and consent processes in light of contemporary debates on a number of these issues. PMID- 20582915 TI - Targeted enrichment of specific regions in the human genome by array hybridization. AB - While whole-genome resequencing remains expensive, genomic partitioning provides an affordable means of targeting sequence efforts towards regions of high interest. There are several competitive methods for targeted capture; these include molecular inversion probes, microdroplet-segregated multiplex PCR, and on array or in-solution capture-by-hybridization. Enrichment of the human exome by array hybridization has been successfully applied to pinpoint the causative allele of Mendelian disorders. This protocol focuses on the application of Agilent 1 M arrays for capture-by-hybridization and sequencing on the Illumina platform, although the library preparation method may be adaptable to other vendors' array platforms and sequencing technologies. PMID- 20582916 TI - Targeted exon sequencing by in-solution hybrid selection. AB - This unit describes a protocol for the targeted enrichment of exons from randomly sheared genomic DNA libraries using an in-solution hybrid selection approach for sequencing on an Illumina Genome Analyzer II. The steps for designing and ordering a hybrid selection oligo pool are reviewed, as are critical steps for performing the preparation and hybrid selection of an Illumina paired-end library. Critical parameters, performance metrics, and analysis workflow are discussed. PMID- 20582917 TI - The application of computer-based tools in obtaining the genetic family history. AB - Family health history is both an adjunct to and a focus of current genetic research, having long been known to be a powerful predictor of individual disease risk. As such, it has been primarily used as a proxy for genetic information. Over the past decade, new roles for family history have emerged, perhaps most importantly as a primary tool for guiding decision-making on the use of expensive genetic testing. The collection of family history information is an important but time-consuming process. Efforts to engage the patient or research subject in preliminary data collection have the potential to improve data accuracy and allow clinicians and researchers more time for analytic tasks. The U.S. Surgeon General, the Centers for Disease Control and Prevention (CDC), and others have developed tools for electronic family history collection. This unit describes the utility of the Web-based My Family Health Portrait (https://familyhistory.hhs.gov) as the prototype for patient-entered family history. PMID- 20582918 TI - Doppler fetal mechanical PR interval prolongation with positive maternal anti-RNP but negative SSA/Ro and SSB/La auto-antibodies. PMID- 20582919 TI - Two- or three-dimensional ultrasonography: which is the best predictor of pulmonary hypoplasia? AB - OBJECTIVE: The aim of our study is to compare the three-dimensional (3D) ultrasound fetal lung volume measurements with two-dimensional (2D) ultrasound biometric parameters in predicting pulmonary hypoplasia (PH). METHODS: From June 2006 to November 2008, we identified 35 fetuses at high risk for developing PH, including premature preterm rupture of membranes (17), fetal skeletal malformations (7), hydrothorax (7), and bilateral renal dysplasia (4). 3D lung volumes adjusted for gestational age (GA) or estimated fetal weight (EFW), thoracic circumference adjusted for GA or femur length, thoracic/abdominal circumference ratio, and thoracic/heart area ratio were measured. RESULTS: Three infants were excluded because no clinical or histological information regarding lung hypoplasia was available. Of the 32 remaining infants, 13 (41%) were diagnosed with PH at postmortem examination or by clinical and radiological examination. 3D lung volume measurements had a better diagnostic accuracy for predicting PH either when adjusted for GA [sensitivity, 12/13 (92%); specificity, 16/19 (84%); positive predictive value 12/15 (80%); negative predictive value, 16/17(94%)] or EFW [sensitivity, 11/13 (85%); specificity, 18/19 (94%); positive predictive value 11/12(92%); negative predictive value, 18/20(90%)] compared to the 2D biometric measurement. CONCLUSION: 3D lung volume measurements seem to be useful in the prenatal prediction of PH. PMID- 20582920 TI - Fetal tricuspid valve Doppler at 11-13 weeks and 6 days: reference values and reproducibility. AB - OBJECTIVE: To determine normal blood flow velocities across the fetal tricuspid valve (TV) at 11-13 weeks and 6 days of gestation and to examine the reproducibility of these measurements. METHODS: A prospective study involving 166 normal singleton pregnancies examined at 11-13 weeks and 6 days was carried out. Descriptive analysis of E- and A-waves' maximum velocities, E/A ratio, duration of the cardiac cycle (C) and diastole (D) and D/C ratio were calculated. Intraobserver and interobserver agreement analysis was performed in a subgroup of 12 cases. RESULTS: Average ( +/- SD) flow velocities were: E-wave, 25.0 ( +/- 4.6) cm/s; A-wave, 42.9 ( +/- 5.9) cm/s; E/A, 0.58 ( +/- 0.07); cardiac cycle, 390 ( +/- 21.1) ms; diastole, 147 ( +/- 18) ms and D/C, 0.38 ( +/- 0.04). Significant correlation was observed between all parameters (except A-wave) and gestational age but not with nuchal translucency (NT). Intraclass correlation coefficients (interobserver, intraobsever examiner 1 and intraobserver examiner 2) were: E-wave, 0.53, 0.53 and 0.64; A-wave, 0.45, 0.46 and 0.49; cardiac cycle, 0.70, 0.79 and 0.84 and diastole, 0.63, 0.85 and 0.82, respectively. CONCLUSIONS: The present study establishes normal Doppler parameters for blood flow across the TV at 11-13 weeks and 6 days and demonstrates that these parameters do not correlate with NT measurement and have good/moderate reproducibility. PMID- 20582921 TI - Syntheses and activities of backbone-side chain cyclic octapeptide ligands with N functionalized phosphotyrosine for the N-terminal SH2-domain of the protein tyrosine phosphatase SHP-1. AB - The protein tyrosine phosphatase SHP-1 plays an important role in many physiological and pathophysiological processes. This phosphatase is activated through binding of ligands to its SH2-domains, mainly to the N-terminal one. Based on a theoretical docking model, backbone-to-side chain cyclized octapeptides were designed as ligands. Assembly of such modelled structures required the synthesis of N-functionalized tyrosine derivatives and their incorporation into the sequence. Because of difficulties encountered in the condensation of N-protected amino acids to the N-alkylated tyrosine-peptide we synthesized and used preformed dipeptide building units. As all attempts to obtain phosphorylated dipeptide units failed, the syntheses had to be performed with a free phenolic function. Use of different N-alkyl or cycloalkyl residues in the N-functionalized side chains allowed to investigate the effect of ring size, flexibility and hydrophobicity of formed lactam bridges on stimulatory activity. All tested linear and cyclic octapeptides stimulate the phosphatase activity of SHP-1. Stimulatory activities of cyclic ligands increase with the chain length of the lactam bridges resulting in increased flexibility and better entropic preformation of the binding conformation. The strong activity of some cyclic octapeptides supports the modelled structure. PMID- 20582922 TI - Severe congenital toxoplasmosis due to a Toxoplasma gondii strain with an atypical genotype: case report and review. PMID- 20582923 TI - The influence of tuber mineral element composition as a function of geographical location on acrylamide formation in different Italian potato genotypes. AB - BACKGROUND: The present study was aimed at examining the effect of tuber mineral composition, distinctive for geographical location, on the expression of acrylamide precursors in three potato genotypes (Arinda, Rossa di Cetica and Sieglinde) in three Italian potato cultivation regions (Puglia, Sicily and Tuscany). RESULTS: Sucrose and amino acids were not correlated with acrylamide formation. In contrast, reducing sugars, limiting with respect to the principal amino acid precursor asparagine, were positively correlated with acrylamide. From analysis of variance, both acrylamide and reducing sugars were not significant for variety but highly significant for location, with higher levels occurring in all three varieties cultivated in Tuscany, followed by Sicily and Puglia respectively. Reducing sugars were negatively correlated with K and Ca and positively correlated with Zn and Cu. Neither N nor P was correlated with reducing sugar content. Path analysis, a statistical technique distinguishing causation and correlation between variables, was implemented to provide additional insight on the interactions between mineral elements and reducing sugars under open field conditions. The variation in reducing sugars in all three varieties was shown to be attributable to Zn. CONCLUSION: Cultivation location has a significant impact on the composition of tuber mineral elements and, as a result, on genotype in the expression of reducing sugars. The negative correlation between Zn and K and the variation in reducing sugar content attributed to the element Zn, which is particularly available in acid soils, are important factors warranting future research aimed at reducing acrylamide formation from an agronomic perspective. PMID- 20582925 TI - The esophageal 'pouch sign': a benign transient finding. AB - OBJECTIVE: Sonographic finding of an esophageal pouch is considered pathognomonic for fetal esophageal atresia (EA). We investigated the clinical significance of this finding. METHODS: Longitudinal sonographic follow-up in pregnancy and neonatal diagnostic work-up was performed in six fetuses with an esophageal neck pouch referred for polyhydramnios and a small or absent stomach. Fetal swallowing and cyclic distension of the pouch were observed for at least 30 min, and follow up examinations were conducted at 2 to 3 weeks intervals. RESULTS: First visualization of the pouch occurred between 18 and 29 weeks of gestation. All pouches were located above the fetal clavicle. No additional anomalies were detected on detailed anatomic survey. Five fetuses had normal karyotypes. At 21 to 33 weeks of gestation, polyhydramnios had resolved, and the stomach was found to be normal in size and shape in all cases. The neonatal work-up ruled out EA in all cases. CONCLUSION: The fetal esophageal pouch sign occurs in structurally normal fetuses and should not be considered pathognomonic for EA or serve as the grounds for pregnancy termination. PMID- 20582927 TI - Chop, chop. PMID- 20582929 TI - Ultrasound assessment of fetal head position. PMID- 20582930 TI - Something new about early pregnancy: decidual biosensoring and natural embryo selection. PMID- 20582931 TI - Evaluation of the CHOP cardiovascular score as a prognostic predictor of outcome in twin-twin transfusion syndrome after laser coagulation of placental vessels in a prospective cohort. AB - OBJECTIVE: To investigate the prognostic value of cardiac function assessment by the previously reported CHOP (Children's Hospital of Philadelphia) cardiovascular score in twin-twin transfusion syndrome (TTTS). METHODS: All consecutive monochorionic pregnancies presenting with TTTS over a 24-month period were evaluated by preoperative echocardiography before percutaneous laser coagulation of chorionic vessels. Each of the 12 items of the CHOP score was evaluated prospectively and the cardiovascular score was categorized into stages using previously published cut-offs. The outcome considered for this study was neonatal survival of neither, one or both twins. RESULTS: In total, 215 pregnancies were enrolled. Due to technical issues, CHOP evaluation was incomplete in 16% of cases and follow-up was unavailable in 12%. Overall, there was a significant relationship between the CHOP score and the Quintero staging system, although this relationship was significantly reduced when parameters used in the Quintero system were removed from the CHOP score. Based upon neonatal survival, the CHOP score did not show any prognostic value regarding overall pregnancy outcome or individual recipient survival. CONCLUSION: Cardiac function assessment using the CHOP score is not of clinical use as a prognostic marker in TTTS. This suggests that cardiac function may not be of interest for preoperative staging when laser coagulation is the first-line treatment, other than to confirm the diagnosis of TTTS requiring surgery. PMID- 20582932 TI - Premature labor after fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: post-procedure management problems. PMID- 20582933 TI - The questionable value of VOCAL indices of perfusion. PMID- 20582934 TI - Effects of roasting and boiling of quinoa, kiwicha and kaniwa on composition and availability of minerals in vitro. AB - BACKGROUND: Andean indigenous crops such as quinoa (Chenopodium quinoa), kiwicha (Amaranthus caudatus) and kaniwa (Chenopodium pallidicaule) seeds are good sources of minerals (calcium and iron). Little is known, however, about mineral bioavailability in these grains. Thus the aim of the present study was to determine the iron, calcium and zinc potential availability in raw, roasted and boiled quinoa, kaniwa and kiwicha seeds. Potential availability was estimated by dialyzability. RESULTS: These seeds are good sources of phenolic compounds and kaniwa of dietary fiber. Their calcium, zinc and iron content is higher than in common cereals. In general, roasting did not significantly affect mineral dialyzability. Conversely, in boiled grains there was an increase in dialyzability of zinc and, in the case of kaniwa, also in iron and calcium dialyzability. CONCLUSION: Taking into account the high content of minerals in Andean grains, the potential contribution of these minerals would not differ considerably from that of wheat flour. Further studies are required to research the effect of extrusion on mineral availability in Andean grains. PMID- 20582935 TI - Sonographic evaluation of the fetal conus medullaris at 20 to 24 weeks' gestation. AB - OBJECTIVE: To determine the normal level of the conus medullaris (CM) of the spinal cord of normal fetuses at 20 to 24 weeks' gestation using abdominal sonography. METHODS: Using a 4 to 8 MHz ultrasound abdominal transducer, CM was imaged in the midsagittal plane with the fetal spine facing toward the transducer. The CM ending level was located by counting the vertebrae caudal starting at T12, which was identified by lowest fetal rib. The CM locations were defined according to their positions relative to the vertebrae. RESULTS: One hundred and ten consecutive pregnant women were included in the study. The CM was clearly demonstrated in 78 (71%) of these cases. Most of the scanned fetuses had the CM ending height adjacent to vertebrae L2, L2-3 inter-space and L3 (73/78, 93%). The L1-2, L2, L2-3, and L3 vertebral groups did not differ in mean gestational weeks, maternal age, or fetal gender. CONCLUSION: The level of the CM can be determined at 20 to 24 weeks' gestation in about 70% of fetuses. Most of the scanned fetuses had the CM ending height adjacent to vertebrae L2, L2-3 vertebral space, and L3 (73/78, 93%). When detected lower than the third lumbar vertebra it should prompt prenatal and postnatal surveillance. PMID- 20582936 TI - How to manage an unresectable or recurrent sialoblastoma. AB - Only 2-5% of all salivary gland tumors occur in children. Sialoblastoma is an extremely rare salivary gland tumor diagnosed at birth or shortly thereafter with significant variability in histological range and clinical course, so that it may be difficult to predict the most appropriate therapy. In cases where surgical removal is not curative or technically feasible, chemotherapy may be attempted. We report herein a patient with progression of a huge partially resected sialoblastoma who was successfully treated with chemotherapy. Systemic chemotherapy with vincristine, actinomycin D, and cyclophosphamide (VAC) seems to be an effective adjuvant or neoadjuvant treatment option for unresectable or recurrent sialoblastoma. PMID- 20582937 TI - Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium. AB - BACKGROUND: Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. PROCEDURE: This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L-asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. RESULTS: Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1 mg/m(2)). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3 mg/m(2)). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. CONCLUSIONS: The combination of bortezomib (1.3 mg/m(2)) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3 mg/m(2) cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT00440726). PMID- 20582938 TI - Measurement of tyrosine hydroxylase transcripts in bone marrow using biopsied tissue instead of aspirates for neuroblastoma. AB - BACKGROUND: Molecular detection of tyrosine hydroxylase (TH) transcripts by quantitative RT-PCR (qRT-PCR) is a sensitive method to detect neuroblastoma (NB) cells in the bone marrow (BM). However, its clinical utility following chemotherapy has not been thoroughly investigated. PROCEDURES: TH transcripts in the BM were measured by qRT-PCR both at diagnosis and during the course of chemotherapy. The results were analyzed with respect to assay timing, tumor volume and histological findings. RESULTS: TH transcripts were detected in 100% of BM aspirates at diagnosis in cases with concurrent tumor involvement in the BM section; however, the proportion of TH transcript positive BM aspirates in cases with concurrent tumor involvement in the BM section gradually decreased following chemotherapy (55.5% after three cycles, 28.6% after six cycles and 0% after nine or more cycles of chemotherapy). Decreased proportion of TH transcript positive BM aspirates was associated with reduced tumor volume in the BM and differentiation of tumors into mature forms during chemotherapy. When qRT-PCR was performed with both aspirated and biopsied tissue during chemotherapy, TH transcripts were detected in BM tissue not only in all of the histology-positive cases but also in some of the histology-negative cases, while the proportion of TH transcript positive BM aspirates was low, even in histology-positive cases. CONCLUSIONS: Measurement of TH transcripts in BM aspirates does not appear to be clinically useful during or after chemotherapy. Therefore, molecular monitoring of NB cells during or after chemotherapy using BM tissue is more optimal than testing on BM aspirates. PMID- 20582939 TI - Regression of a congenital mesoblastic nephroma. AB - Histologically, the cellular variant of congenital mesoblastic nephroma (CMN) is very similar to another rare tumor of infancy, infantile fibrosarcoma (IFS). In addition to the histologic similarities, these tumor types share cytogenetic abnormalities including translocation t(12;15)(p13;q25). We describe herein the case of a child who did not have immediate surgical resection of a CMN and whose tumor was untreated for 8 months. During that time, the tumor demonstrated a significant degree of regression. The shared translocation with IFS, a tumor with well-documented potential for spontaneous regression, suggests that this genetic abnormality may have contributed to the favorable clinical course. PMID- 20582940 TI - Long-term survivors of childhood cancer report quality of life and health status in parity with a comparison group. AB - BACKGROUND: There is a need for more knowledge about how survivors of childhood cancer perceive their lives and what influence current health status has on their quality of life. The purpose was to describe this among a group of long-term survivors and among a comparison group. PROCEDURE: Telephone interviews were performed with a cohort of 246 long-term survivors and 296 randomly selected from the general population using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW). The participants nominated the areas they considered to be most important in life and rated the current status of each area on a seven-point category scale. An overall individual index score was calculated as a measure of quality of life. Self-reported health status was assessed using the Short Form Health Survey (SF-36). RESULTS: Long-term survivors rated their overall quality of life and self-reported health status almost in parity with the comparison group. In both groups, family life, relations to other people, work and career, interests and leisure activities were the areas most frequently reported to influence quality of life. The survivors only differed from the comparison group on one of eight SF-36 scales reflecting problems with daily activities owing to physical health. CONCLUSIONS: Health status was not shown to have a major impact on overall quality of life, indicating that health and quality of life should be evaluated distinctively as different constructs. This should be taken in consideration in clinical care of children with childhood cancer and long-term survivors. PMID- 20582941 TI - Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP). AB - Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft tissue tumor in children. DFSP is characterized by a specific fusion of the platelet-derived growth factor beta (PDGFbeta) with the collagen type 1alpha1 (COL1alpha1) gene which renders these tumors responsive to targeted therapy with tyrosine kinase inhibitors, such as imatinib mesylate, as is reported in adults. In the current report, we describe the first small pediatric DFSP series, in which response to imatinib mesylate contributed to successful treatment outcome. PMID- 20582942 TI - Paraoxonase gene mutations in amyotrophic lateral sclerosis. AB - Three clustered, homologous paraoxonase genes (PON1, PON2, and PON3) have roles in preventing lipid oxidation and detoxifying organophosphates. Recent reports describe a genetic association between the PON genes and sporadic amyotrophic lateral sclerosis (ALS). We now report that in genomic DNA from individuals with familial and sporadic ALS, we have identified at least 7 PON gene mutations that are predicted to alter PON function. PMID- 20582943 TI - Acute necrotizing encephalopathy during novel influenza A (H1N1) virus infection. AB - A novel swine-origin influenza A (H1N1) virus was recently identified in Mexico. Some cases of infection with neurological complications have been reported to date. We report a case of acute necrotizing encephalopathy associated with the novel H1N1 virus in a 2-year-old European girl who suddenly developed fever, seizures, and altered mental status. Brain and spinal cord magnetic resonance imaging showed bilateral symmetrical lesions of the insulae, thalami, geniculate bodies, and pons tegmentum suggestive of an acute necrotizing encephalopathy. An involvement of meninges and spinal cord was observed configuring an acute necrotizing meningoencephalomyelitis. PMID- 20582944 TI - Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats. AB - OBJECTIVE: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. METHODS AND RESULTS: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. INTERPRETATION: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect. PMID- 20582945 TI - Steps forward in neuroblastoma genetic epidemiology. PMID- 20582946 TI - Stromal and epithelial predominant Wilms tumours have an excellent outcome: the SIOP 93 01 experience. AB - BACKGROUND: Wilms tumour (WT) has various subtypes that are correlated with prognosis and require distinct therapy. Stromal predominant (SpWT) and epithelial WT (EpWT) have previously been associated with a good outcome. The current analysis describes the outcome and (tumour) characteristics of all patients with SpWT, EpWT, including highly differentiated epithelial type (HDET), treated according to the International Society of Pediatric Oncology (SIOP) 93-01 study. PROCEDURE: All children older than 6 months and below 18 years of age with localized or metastatic WT and intermediate risk (IR) histology or HDET treated with pre-operative chemotherapy were included in the present analysis. RESULTS: A total of 1,389 eligible patients had IR or HDET histology: 1% HDET, 4% EpWT, 10% SpWT, and 85% other IR. For EpWT/HDET, 93% had stage I/IIN-, 5-year EFS was 90.2% and overall survival of (OS) 98.4%, as compared to 84.0% and 92.5% in other IR histology (NS). Stage I EpWT/HDET had a significant better outcome than stage I of other IR. In SpWT 82% of cases had stage I/IIN-; 5-year EFS was 94.3% and OS 99.2%, significantly better compared to other IR histology. All patients with stage I are alive (2/149 relapses); 3/52 stage IIN-, 2/21 stage IIN+/III, and 6/12 stage IV patients relapsed (1 deceased per stage group). CONCLUSIONS: The good outcome for EpWT and SpWT generally is very good which may be related to low age and low stage in most cases. A reduction of treatment intensity and/or duration may be justified especially for low stage SpWT that has an EFS close to 100%. PMID- 20582947 TI - Visual cortical neurophysiology with ipsilateral sensorimotor cortical lesions. PMID- 20582949 TI - Hypomyelination versus delayed myelination. PMID- 20582950 TI - Survivorship outcomes research based on record linkage. PMID- 20582951 TI - Morbidity of pandemic H1N1 influenza in children with cancer. AB - BACKGROUND: To define the mortality and the current impact of the H1N1 pandemic in pediatric hematology-oncology centers, we performed a specific survey. PROCEDURE: Pharyngeal swabs from patients with fevers of unknown origin, flu-like symptoms or bronchopneumonia were screened for H1N1 using PCR. RESULTS: Sixty-two patients with documented H1N1 infection were reported: 16 had recently stopped therapy, 2 were at the diagnosis stage, and 44 were receiving therapy. The clinical course was severe (requiring ICU admission) in only 1 patient, moderate (requiring hospital admission) in 38, and mild in the remaining 23 (37%), treated as outpatients. While none of the patients died of H1N1-related complications, two patients died of progressive cancer; in all of the remaining cases, symptoms resolved within 11 days. The clinical course was complicated by respiratory distress or bronchopneumonia in 10 cases. Oseltamivir was given to 82% of patients. Chemotherapy was temporarily withdrawn in 54% of cases for a median time of 21 days (range, 4-43 days). CONCLUSION: H1N1 infection in children with cancer was not reported as the cause of death in any case but resulted in reduced intensity of anti-cancer therapy. PMID- 20582954 TI - Yield of systematic transcranial Doppler in patients with transient ischemic attack. AB - OBJECTIVE: Urgent evaluation and treatment of transient ischemic attack (TIA) patients in a dedicated TIA clinic may reduce the 90-day stroke risk by 80%. ABCD2 (Age, Blood pressure, Clinical features, Duration, Diabetes) score and magnetic resonance imaging abnormalities help to identify patients at high risk of stroke. Our aim was to determine whether the use of transcranial Doppler (TCD) examination on arrival at the TIA clinic yields additional information that facilitates the identification of patients at high risk of stroke recurrence. METHODS: Between January 2003 and December 2007, 1,881 patients were admitted to SOS-TIA clinic (a TIA clinic with around-the-clock access). Clinical and vascular assessment included TCD performed by a neurologist immediately after admission. Stroke prevention measures were initiated on arrival, in accordance with guidelines. All patients were followed for 1 year after presentation to the SOS TIA clinic. RESULTS: A total of 1,823 TCD examinations were performed within 4 hours of admission. Intracranial narrowing or occlusion was found in 8.8% of patients, and was independently associated with age, hypertension, and diabetes. After 1-year follow-up on best preventive therapy, the incidence of recurrent vascular events (intracranial revascularization for TIA recurrence, stroke, myocardial infarction, and vascular death combined) was 7.0% in patients with intracranial narrowing or occlusion and 2.4% in those without (log-rank, p = 0.007). The hazard ratio of combined outcome for the presence of intracranial narrowing or occlusion was 2.29 (95% confidence interval [CI], 1.15-4.56; p = 0.02) in multivariate analysis including age, gender, hypertension, and diabetes, and was 2.50 (95%CI, 1.24-5.05; p = 0.01) in multivariate analysis including ABCD2 score > or =4. INTERPRETATION: Immediate TCD examination on arrival at the TIA clinic is feasible and could help to identify patients at high risk of vascular events recurrence. This study supports a systematic intracranial vascular examination in the initial management of TIA. PMID- 20582955 TI - Pediatric moyamoya disease: An analysis of 410 consecutive cases. AB - OBJECTIVE: Moyamoya disease (MMD) is a cerebrovascular occlusive disease of the bilateral internal carotid arteries that causes a compensatory abnormal vascular network at the base of brain. The rare incidence and various surgical techniques applied have limited the clinical research on MMD. METHODS: We conducted a retrospective analysis of the surgical outcome of 410 pediatric MMD patients. All patients were treated in a relatively uniform scheme at a single institution. The surgical procedures consisted of bilateral encephaloduroarteriosynangiosis augmented by bifrontal encephalogaleo-/periosteal synangiosis. Logistic regression analyses were applied to reveal the prognostic factors for surgical outcome. RESULTS: The overall clinical outcome was excellent in 66%, good in 15%, fair in 15%, and poor in 4% of the patients. Therefore, 81% of the patients had a favorable clinical outcome (excellent and good). Multivariate analyses revealed that infarction on presentation was associated with unfavorable clinical outcome (odds ratio [OR], 2.85; 95% confidence interval [CI], 1.49-5.46; p < 0.01) and decreased vascular reserve only on single-photon emission computerized tomography (OR, 0.07; 95% CI, 0.01-0.52; p < 0.01), with favorable clinical outcome. INTERPRETATION: Our results indicate that an early diagnosis and active intervention before establishment of irreversible hemodynamic change are essential to achieve a favorable clinical outcome in children with MMD. PMID- 20582956 TI - XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL. AB - BACKGROUND: Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X-linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies. PROCEDURE: XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome. RESULTS: XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/10(5) MNC, P < 0.0001) indicating a post-transcriptional regulation of XIAP expression. In patients with T-cell ALL, poor prednisone response was associated with increased XIAP expression (median: 2.8 in good vs. 5.8 in poor responders; P = 0.005). Similarly, T-cell ALL patients suffering adverse events showed higher initial XIAP levels than patients in continuous complete remission (CCR) (median: 2.7 in patients in CCR vs. 5.6 in patients suffering adverse events; P = 0.007). XIAP inhibition using the low-molecular weight SMAC mimetic LBW242 resulted in a significant increase of prednisone induced apoptosis in vitro. CONCLUSION: In childhood ALL compared to control bone marrow, the expression of the apoptosis inhibitor XIAP is highly increased by post-transcriptional regulation. The association with poor in vivo glucocorticoid response and outcome in T-cell ALL suggests XIAP inhibition as a promising novel approach for the treatment of resistant ALL. PMID- 20582957 TI - Successful treatment of multiply relapsed lymphoma with rituximab as a single agent. AB - The treatment of non-Hodgkin lymphoma (NHL) is an example of the successful therapy of cancer in children; the cure rate overall at approximately 80%. Unfortunately, relapsed NHL has a dismal prognosis, and the customary treatment is highly toxic chemotherapy followed by hematopoietic stem cell transplantation (HSCT). A child with relapsed T-cell rich B-NHL was treated with rituximab alone. This was delivered in eight doses after the recurrence of disease after high-dose chemotherapy and allogenic HSCT that was undertaken for the first relapse. Eight years after the last dose of rituximab he remains in complete remission. PMID- 20582958 TI - How do leukemic stem cells find their niche? PMID- 20582959 TI - Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease. AB - BACKGROUND: L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. PROCEDURE: Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. RESULTS: SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. CONCLUSION: L-Arg levels in steady state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. PMID- 20582960 TI - Molecular diagnosis of childhood acute leukemia: Serbian experience. PMID- 20582961 TI - Fine-tuning treatment for Wilms Tumor patients: Which way should we turn the dial? PMID- 20582962 TI - Topotecan and etoposide combination to test neuroblastoma in pediatric preclinical testing program. PMID- 20582963 TI - Plasmablastic lymphoma of oral cavity in a HIV-negative child. PMID- 20582964 TI - Placing of tunneled central venous catheters prior to induction chemotherapy in children with acute lymphoblastic leukemia. AB - BACKGROUND: Tunneled central venous catheters (CVCs) are inevitable in children with acute lymphoid leukemia (ALL). The aim of this study was to evaluate the risk of CVC-related complications in children with ALL in relation to timing of catheter placement and type of catheter. PROCEDURE: All children hospitalized from January 2000 to March 2008 with newly diagnosed ALL and with double-lumen total implantable devices (TIDs) or tunneled external catheters (TEs) were included retrospectively. We only used data related to the patient's first catheter. RESULTS: We included 98 children; 35 received a TID and the remaining 63 received a TE. A total number of 29,566 catheter days and 93 catheter associated blood stream infections (CABSI) was identified. We found a CABSI rate of 3.1/1,000 catheter days (5.4/1,000 catheter days for TEs and 1.4/1,000 catheter days for TIDs, incidence rate ratio (IRR) 3.82 (95% CI 2.37-6.35) P = 0.0001). No difference was found in CABSI between neither early versus later placed TIDs (IRR = 0.99 (95% CI 0.41-2.45) P = 0.98) nor early versus later placed TEs (IRR = 0.81 (95% CI 0.40-1.86) P = 0.54). We found no difference between early and later placed catheters regarding non-elective removal (RR = 0.86 (95% CI 0.72-1.03) P = 0.09). TEs had a higher risk of non-elective removal compared with TIDs (RR = 3.95 (95% CI 1.88-8.29) P < 0.001). CONCLUSIONS: The study did not find that children with ALL and with early placed CVCs experienced significantly more complications compared with children with late placed catheters. This study found that children with ALL and TEs experienced more complications than children with TIDs. PMID- 20582965 TI - High health-related quality of life among long-term survivors of childhood acute lymphoblastic leukemia. AB - BACKGROUND: Health-related quality of life (HRQoL) was assessed in a cohort of long-term childhood acute lymphoblastic leukemia (ALL) survivors. PROCEDURE: Rand 36-Item health Survey (RAND-36) was used to assess subjective HRQoL in 74 survivors of ALL an average of 20 years after the diagnosis. Cranial irradiation had been administered to 46 of the survivors, while 28 survivors had solely been treated with chemotherapy. The control group consisted of 146 healthy young adults selected from local population registry. Survivors were examined by a physician and late effects were graded using the Common Terminology Criteria for Adverse Events (CTCAEv3). RESULTS: ALL survivors achieved significantly higher scores than the controls on three of the eight HRQoL subscales; role limitations due to emotional problems (P = 0.030), mental health (P = 0.030) and vitality (P = 0.004). In comparison to controls, survivors with a follow-up of more than 20 years had significantly higher scores on vitality (P = 0.006) and mental health (P = 0.011). Survivors with severe (grade 3 and 4) late effects scored significantly better than controls on vitality (P = 0.043) and mental health (P = 0.040). Patients who had been treated for an ALL relapse and had received the most intensive chemo- and radiotherapy had significantly higher scores on mental health (P = 0.004) and vitality (P = 0.004) than the controls. CONCLUSIONS: Long term survivors of childhood ALL reported equal or better HRQoL in RAND-36. Higher HRQoL scores were associated with more severe late effects and intensive therapy. Our findings support the idea of response bias. PMID- 20582966 TI - Secondary adrenal insufficiency in an infant after intrathecal triple chemotherapy. AB - Intrathecal triple chemotherapy (ITT) with hydrocortisone, methotrexate, and cytarabine is commonly used in treatment of pediatric acute leukemias. While prolonged systemic administration of corticosteroids is known to suppress the hypothalamic-pituitary-adrenal axis, there have been no reports describing this effect following administration of ITT. We present an infant with relapsed acute myelogenous leukemia who developed clinically significant central adrenal axis suppression following six doses of ITT over 3 weeks, proven by corticorelin stimulation test. As multiple pediatric leukemia protocols incorporate ITT, particularly in infants, we feel that ITT should be considered as a potential source of adrenal axis suppression. PMID- 20582967 TI - Solitary, extracutaneous, skull-based juvenile xanthogranuloma. AB - We report a case of an 18-month-old female who presented an occipital bone lesion with progressive growth. Imaging studies showed a left extradural, skull-based tumor partially occupying the posterior fossa. Histopathological and immunohistochemical studies confirmed a juvenile xanthogranuloma (JXG). Partial surgical resection, chemotherapy, and conformational radiotherapy were used. Exclusive extracutaneous JXG with an intracranial, vertebral, or skull-based localization is extremely rare. PMID- 20582968 TI - Incidence of skin lesions of Kaposi sarcoma in HIV-positive children. PMID- 20582969 TI - Tigecycline treatment of multi-drug-resistant Corynebacterium jeikeium infection in a child with relapsing and refractory acute lymphoblastic leukemia. AB - Corynebacterium jeikeium has been recognized as an important cause of infection, particularly among neutropenic patients who have central venous catheter (CVC). Routine use of tigecycline in children is not yet approved. Here in we present a child with relapsed-refractory lymphoblastic leukemia who was successfully treated with tigecyline due to multi-drug-resistant C. jeikeium sepsis without removal of CVC. Our case highlights the use of tigecycline where there are no alternatives. Further studies regarding the efficacy and safety of tigecycline in pediatric patients are needed. PMID- 20582970 TI - Randomized trial to compare LSA2L2-type maintenance therapy to daily 6 mercaptopurine and weekly methotrexate with vincristine and dexamethasone pulse for children with acute lymphoblastic leukemia. AB - BACKGROUND: A total of 201 pediatric cases of acute lymphoblastic leukemia were treated with the ALL-96 protocol by the Kyushu-Yamaguchi Children's Cancer Study Group. PROCEDURE: Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). All of the patients were classified into standard-risk (SR) or high-risk (HR) groups and were randomly assigned to receive maintenance therapy with either LSA2L2-type or 6-mercaptopurine (6-MP)/methotrexate (MTX) with vincristine (VCR) and dexamethasone (DEX) pulse in both risk groups. RESULTS: The 7-year event-free survival (EFS) and overall survival (OS) rates in the entire study population were 72.1% (95% CI: 68.0-76.2%) and 84.8% (95% CI: 79.7-89.9%), respectively, and the EFS of the SR patients (85.3% [95% CI: 78.2-92.4%]) was significantly better than HR patients (62.4% [95% CI: 52.2-72.6%]) (P = 0.0007). CONCLUSIONS: There were no differences in the EFS between the different maintenance therapies in each risk group; however, grade IV liver toxicity occurred more often in the patients receiving 6-MP/MTX with VCR and DEX therapy than in patients receiving LSA2L2. PMID- 20582971 TI - Childhood, adolescent, and young adult cancer survivors research program of British Columbia: objectives, study design, and cohort characteristics. AB - BACKGROUND: The Childhood, Adolescent, and Young Adult Cancer Survivors Research Program (CAYACS) has been established in the province of British Columbia (BC), Canada, to carry out research into late effects and survivor care in multiple domains, and to inform policy and practice. PROCEDURE: This program identifies a survivor cohort and comparison groups from population-based registries and links their records to population-based files of outcomes and outcome determinants, to create a research database and conduct studies of long-term outcomes and care. RESULTS: The initial cohort consisted of all 5-year survivors of cancer or a tumor diagnosed under age 25 years from 1970 to 1995, who were residents in BC at the time of diagnosis, and followed till 2000 (3,841 subjects). Seven percent have died, and 77% have treatment information available. Data on death and second cancer occurring in BC are available. Late morbidity and healthcare utilization information is available for 68% of survivors (79% of those diagnosed from 1981). Education outcomes are available for 71% of those born during 1978-1995 and diagnosed under age 15 years. CONCLUSIONS: Use of registries, administrative databases, and record linkage methodologies is a cost-effective and comprehensive means to conduct survivorship research. This program should add to knowledge of risks of late effects and impacts on care, inform development of strategies to manage risks, evaluate the effects of surveillance and interventions, and assess new risks as the cohort ages, more recent survivors enter the cohort, and treatments change. PMID- 20582972 TI - Initial testing of the replication competent Seneca Valley virus (NTX-010) by the pediatric preclinical testing program. AB - BACKGROUND: Seneca Valley virus (NTX-010) is a non-recombinant, replication competent RNA virus that is undergoing phase 1 clinical trials in adults for tumors with neuroendocrine characteristics. Here we have evaluated the antitumor activity of NTX-010 administered systemically. PROCEDURES: In vitro NTX-010 was tested against 23 cell lines exposed for 96 hr at 1 x 10(-4) to 10(4) viral particles (vp)/cell. In vivo NTX-010 was administered intravenously once at 3 x 10(12) vp/kg. Three measures of antitumor activity were used: (1) an objective response measure modeled after the clinical setting; (2) a treated to control (T/C) tumor volume measure; and (3) a time to event (fourfold increase in tumor volume for solid tumor models), measure based on the median event-free survival (EFS) of treated and control animals for each xenograft. RESULTS: In vitro NTX 010 demonstrated a marked cytotoxic effect in a subset of the cell lines from the neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma panels. In vivo the most consistent activity was observed for the rhabdomyosarcoma and the neuroblastoma panels, with all four of the alveolar rhabdomyosarcoma xenografts and four of five neuroblastoma xenografts achieving CR or maintained CR. Objective responses were also observed in the rhabdoid tumor, Wilms tumor, and glioblastoma panels. CONCLUSIONS: NTX-010 demonstrated a high level of activity both in vitro and in vivo. Further analysis of existing testing and molecular characterization data may help define the biological characteristics of cancer cells that are associated with response to NTX-010. PMID- 20582974 TI - Potential response to curcumin in infantile hemangioendothelioma of the liver. AB - A case of life-threatening infantile hemangioendothelioma of the liver in a 6 month-old infant treated successfully with the dietary supplement curcumin is reported, with 6-year follow-up. Implications for pathogenesis based on sites of action of curcumin are considered. PMID- 20582975 TI - Is there an association between bicuspid aortic valve and neuroblastoma? AB - An association has been reported between neuroblastoma and congenital heart disease, frequently bicuspid aortic valve [Holzer and Franklin. Arch Dis Child 2002;87:61-64; George et al. J Pediatr 2004;144:444-448; Friedman et al. Pediatr Cardiol 1998;19:480-481; Monte et al. Am J Pediatr Hematol Oncol 1985;7:109-116]. To evaluate this in a large patient group with neuroblastoma, we examined echocardiograms of patients with neuroblastoma from 1987 to January 2007 to determine if there was a higher incidence of bicuspid aortic valves compared to the general population without neuroblastoma. We found that only 0.7% of neuroblastoma patients had the congenital heart defect of bicuspid aortic valves compared with 1-2% in the general population [Braverman et al. Curr Prob Cardiol 2005;30:470-522]. Our data show that neuroblastoma is not associated with bicuspid aortic valves. PMID- 20582973 TI - Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. AB - BACKGROUND: Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other. PROCEDURE: We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with eight SCN progeny of a sperm donor and six different mothers. RESULTS: One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor's spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. CONCLUSIONS: The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process. PMID- 20582976 TI - Pleomorphic xanthoastrocytoma in children and adolescents. AB - BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor occurring primarily in children and young adults. The superficial location of the tumor facilitates gross total resection (GTR) thus conferring a relatively favorable outcome with a reported 10-year overall survival (OS) of 70%. PROCEDURE: A retrospective case analysis of children and adolescents diagnosed and treated with PXA in our institution between January 1980 and March 2009 and a literature review. RESULTS: 85.7% of our patients with a GTR were recurrence free. Only one of seven patients with less than a GTR did not recur and median time to recurrence was under 1 year in patients who did not have a GTR. Two of three patients with anaplastic features or malignant transformation at initial presentation progressed. Five-year OS and recurrence free survival (RFS) was 85.7% and 49%, respectively. CONCLUSIONS: GTR is the preferred treatment modality for PXA. Anaplastic features, though uncommon at initial presentation, confer a less favorable outcome. The role of adjuvant therapy with primary and recurrent anaplastic PXAs, especially when complete resection is not feasible, warrants further study. PMID- 20582977 TI - Chemokine/chemokine receptor interactions in extramedullary leukaemia of the skin in childhood AML: differential roles for CCR2, CCR5, CXCR4 and CXCR7. AB - Chemokine receptor/ligand interactions orchestrate the migration of cells to peripheral tissues such as the skin. We analysed chemokine receptor expression by acute myeloid leukaemic (AML) cells present in peripheral blood (n = 7), bone marrow (n = 6), or skin (n = 11) obtained from 15 paediatric AML patients with skin involvement and in 10 AML patients without skin involvement. High percentages of circulating CCR2(pos) AML cells were only detected in patients with extramedullary disease. Skin-residing AML cells displayed a different set of receptors in situ, namely: CCR5, CXCR4, CXCR7 and CX3CR1. These results suggest the involvement of different chemokine/chemokine receptor interactions in homing and retention of AML blasts in the skin. PMID- 20582979 TI - Neuroblastoma of unknown primary site with periorbital bone metastasis in a child. AB - Neuroblastoma is the second most common solid tumor in children. Most tumors arise in the adrenal glands or paravertebral region. Rarely, patients present with metastatic disease but no primary site can be found despite extensive imaging. We report here a patient with a large periorbital bone metastasis and bone marrow involvement but with no known primary site. PMID- 20582978 TI - Osteosarcoma in children 5 years of age or younger at initial diagnosis. AB - BACKGROUND: Since osteosarcoma is extremely rare in children < or =5 years of age, we sought to investigate if tumor characteristics, treatment strategies, and outcomes differ compared to older patients. PROCEDURE: Patients <20 years of age with high-grade osteosarcoma reported to national SEER database from 1973 to 2006 were separated into two groups based on age at diagnosis: < or =5 years (n = 49) and 6-19 years (n = 1,687). Patient, tumor, and treatment characteristics were compared using Fisher exact tests. Overall survival was estimated by Kaplan-Meier methods and compared using log-rank tests and Cox models. RESULTS: Patients < or =5 years had higher proportions of osteosarcoma arising from the upper limb compared to older patients (24.5% vs. 11.2%; P = 0.006). These very young patients had a significantly higher proportion of telangiectatic histology (10.2% vs. 2.9%; P = 0.017). Sex, metastatic status, race, or ethnicity did not differ by age. A higher proportion of very young patients was treated with amputation (55.2% vs. 27.3%; P = 0.002). Five-year overall survival was inferior for patients with localized osteosarcoma 5 years of age or younger compared to older children (51.9% vs. 67.3%; P = 0.03). After controlling for metastatic status, year of diagnosis, and tumor site, the hazard ratio for death in very young patients was 1.6 (95% confidence interval 1.02-2.36; P = 0.04) compared to older patients. CONCLUSIONS: Tumor characteristics, treatment, and outcomes differ among children < or =5 years of age compared to older pediatric patients. These differences may reflect differences in tumor biology. PMID- 20582980 TI - A novel G473A mutation in the glucose-6-phosphate dehydrogenase gene. AB - Hereditary deficiency in human glucose-6-phosphate dehydrogenase (G6PD) is mostly caused by single nucleotide change in the G6PD gene which leads to single amino acid substitution. In 104 cases of Chinese children with G6PD deficiency, RT-PCR DGGE (denaturing gradient gel electrophoresis) combined with DNA sequencing was carried out to screen the mutations within the coding region of G6PD gene. A novel missense mutation (G473A), predicting a Cys-to-Tyr substitution at codon 158, was identified in a male infant patient and confirmed in his mother. This G6PD variant (158 Tyr) showed decreased enzyme activity, belonging to WHO Class II. We designated this variant as G6PD Shenzhen by the birthplace of the propositus. PMID- 20582981 TI - MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: a report from the Children's Oncology Group. AB - BACKGROUND: The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li-Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro. PROCEDURE: We genotyped children (n = 575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population. RESULTS: The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; P = 0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961. CONCLUSIONS: The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy. PMID- 20582982 TI - Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare malignancy in the United States, which is considered a low-risk country. METHODS: We searched the surveillance, epidemiology, and end results (SEER) database for patients with NPC who were diagnosed from 1988 to 2006. We compared the clinical features and outcomes of children and adolescents (<20 years old) and adults. RESULTS: The incidence for children and adolescents was 0.5 per million person-years versus 8.4 in adults. NPC was less rare in black children and adolescents (incidence, 1.5 per million person-years). Our search criteria retrieved 129 children and adolescents and 5,885 adults. Black children and adolescents represented 34.9% of patients below the age of 20 years. Younger patients had distinct features with advanced stages more frequently observed (31% and 46% of children and adolescents had stages III and IV, respectively) and 87% had WHO type III histology. Outcome was better in children and adolescents with 5-year NPC-specific survival of 83% +/- 3.9% compared to 62% +/- 0.8% in adults (P < 0.001). In a multivariate model, the following factors affected the outcome: age, race, stage, and histologic type. Young adults (20-45 years old) had almost double the risk of NPC-specific mortality when compared to children and adolescents [hazards ratio (HR), 1.93; P = 0.0077]. Children and adolescents with NPC were at higher risk of getting second cancer than adults (observed-to-expected ratio of 4.36 in children and adolescents; vs. 1.41 in adults; both were significantly higher than general population). CONCLUSION: Despite the use of similar treatment approaches, NPC in children and adolescents may have different biologic features. Young patients are at higher risk of developing therapy related complications, including second cancer. PMID- 20582983 TI - WT1 peptide immunotherapy for cancer in children and young adults. AB - Wilms tumor gene (WT1) can be overexpressed in childhood cancers. We evaluated the efficacy of WT1 vaccination for five children with solid cancer or acute leukemia. WT1 vaccine was administered to HLA-A*2402-positive patients with WT1 overexpressing residual tumor despite prior conventional treatment. One patient showed complete response and one patient showed stable disease according to the Response Evaluation Criteria in Solid Tumors; the remaining three showed progressive disease. Treatment-related adverse effects were limited to local injection site erythema. These results suggest that WT1 vaccination has therapeutic potential, but any beneficial effect may be insufficient in the presence of gross residual disease. PMID- 20582984 TI - Upregulation of K2P5.1 potassium channels in multiple sclerosis. AB - OBJECTIVE: Activation of T cells critically depends on potassium channels. We here characterize the impact of K(2P)5.1 (KCNK5; TASK2), a member of the 2-pore domain family of potassium channels, on T-cell function and demonstrate its putative relevance in a T-cell-mediated autoimmune disorder, multiple sclerosis (MS). METHODS: Expression of K(2P)5.1 was investigated on RNA and protein level in different immune cells and in MS patients' biospecimens (peripheral blood mononuclear cells, cerebrospinal fluid cells, brain tissue specimen). Functional consequences of K(2P)5.1 expression were analyzed using pharmacological modulation, small interfering RNA (siRNA), overexpression, electrophysiological recordings, and computer modeling. RESULTS: Human T cells constitutively express K(2P)5.1. After T-cell activation, a significant and time-dependent upregulation of K(2P)5.1 channel expression was observed. Pharmacological blockade of K(2P)5.1 or knockdown with siRNA resulted in reduced T-cell functions, whereas overexpression of K(2P)5.1 had the opposite effect. Electrophysiological recordings of T cells clearly dissected K(2P)5.1-mediated effects from other potassium channels. The pathophysiological relevance of these findings was demonstrated by a significant K(2P)5.1 upregulation in CD4(+) and CD8(+) T cells in relapsing/remitting MS (RRMS) patients during acute relapses as well as higher levels on CD8(+) T cells of clinically isolated syndrome, RRMS, and secondary progressive multiple sclerosis patients during clinically stable disease. T cells in the cerebrospinal fluid from MS patients exhibit significantly elevated K(2P)5.1 levels. Furthermore, K(2P)5.1-positive T cells can be found in inflammatory lesions in MS tissue specimens. INTERPRETATION: Selective targeting of K(2P)5.1 may hold therapeutic promise for MS and putatively other T-cell mediated disorders. PMID- 20582985 TI - Retinal fractals and acute lacunar stroke. AB - This study aimed to determine whether retinal fractal dimension, a quantitative measure of microvascular branching complexity and density, is associated with lacunar stroke. A total of 392 patients presenting with acute ischemic stroke had retinal fractal dimension measured from digital photographs, and lacunar infarct ascertained from brain imaging. After adjusting for age, gender, and vascular risk factors, higher retinal fractal dimension (highest vs lowest quartile and per standard deviation increase) was independently and positively associated with lacunar stroke (odds ratio [OR], 4.27; 95% confidence interval [CI], 1.49-12.17 and OR, 1.85; 95% CI, 1.20-2.84, respectively). Increased retinal microvascular complexity and density is associated with lacunar stroke. PMID- 20582986 TI - Environmental neurotoxin-induced progressive model of parkinsonism in rats. AB - OBJECTIVE: Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. METHODS: We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism. RESULTS: Cycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). alpha-Synuclein (alpha-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified alpha-syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and alpha syn aggregates in the SN. INTERPRETATION: Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. PMID- 20582987 TI - T2*-weighted magnetic resonance imaging with hyperoxia in acute ischemic stroke. AB - OBJECTIVE: We describe the first clinical application of transient hyperoxia ("oxygen challenge") during T2*-weighted magnetic resonance imaging (MRI), to detect differences in vascular deoxyhemoglobin between tissue compartments following stroke. METHODS: Subjects with acute ischemic stroke were scanned with T2*-weighted MRI and oxygen challenge. For regions defined as infarct core (diffusion-weighted imaging lesion) and presumed penumbra (perfusion-diffusion mismatch [threshold = T(max) > or =4 seconds], or regions exhibiting diffusion lesion expansion at day 3), T2*-weighted signal intensity-time curves corresponding to the duration of oxygen challenge were generated. From these, the area under the curve, gradient of incline of the signal increase, time to maximum signal, and percentage signal change after oxygen challenge were measured. RESULTS: We identified 25 subjects with stroke lesions >1ml. Eighteen subjects with good quality T2*-weighted signal intensity-time curves in the contralateral hemisphere were analyzed. Curves from the diffusion lesion had a smaller area under the curve, percentage signal change, and gradient of incline, and longer time to maximum signal (p < 0.05, n = 17) compared to normal tissue, which consistently showed signal increase during oxygen challenge. Curves in the presumed penumbral regions (n = 8) showed varied morphology, but at hyperacute time points (<8 hours) showed a tendency to greater percentage signal change. INTERPRETATION: Differences in T2*-weighted signal intensity-time curves during oxygen challenge in brain regions with different pathophysiological states after stroke are likely to reflect differences in deoxyhemoglobin concentration, and therefore differences in metabolic activity. Despite its underlying complexities, this technique offers a possible novel mode of metabolic imaging in acute stroke. PMID- 20582988 TI - Clinician-scientist training: a perspective from across the pond. PMID- 20582989 TI - Reply: Predicted pathogenic missense mutation of PGRN found in a normal control. PMID- 20582990 TI - Multiple sclerosis and viruses. AB - Discussing the problem of multiple sclerosis and viruses should not be limited to reviewing the epidemiological evidence in favor, or against, a particular candidate, such as Epstein-Barr virus or human herpes virus 6. In this text, I discuss the difficulty of going from association to causation in human epidemiology; the fact that viruses can trigger or prevent autoimmunity; the problem of our very limited knowledge of the viruses that we harbor as part of our metagenome; and the role of such viral flora in multifactorial diseases and also, possibly, in health. PMID- 20582991 TI - Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease. AB - OBJECTIVE: Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels. METHODS: In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels. RESULTS: Fifty-eight randomly selected IPD patients were compared to 58 age- and sex-matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels. INTERPRETATION: IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. PMID- 20582992 TI - Does body mass index increase risk of hemorrhagic stroke? PMID- 20582993 TI - Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. AB - OBJECTIVE: L-dopa is the most widely used and most effective therapy for Parkinson disease (PD), but chronic treatment is associated with motor complications in the majority of patients. It has been hypothesized that providing more continuous delivery of L-dopa to the brain would reduce the risk of motor complications, and that this might be accomplished by combining L-dopa with entacapone, an inhibitor of catechol-O-methyltransferase, to extend its elimination half-life. METHODS: We performed a prospective 134-week double-blind trial comparing the risk of developing dyskinesia in 747 PD patients randomized to initiate L-dopa therapy with L-dopa/carbidopa (LC) or L dopa/carbidopa/entacapone (LCE), administered 4x daily at 3.5-hour intervals. The primary endpoint was time to onset of dyskinesia. RESULTS: In comparison to LC, patients receiving LCE had a shorter time to onset of dyskinesia (hazard ratio, 1.29; p = 0.04) and increased frequency at week 134 (42% vs 32%; p = 0.02). These effects were more pronounced in patients receiving dopamine agonists at baseline. Time to wearing off and motor scores were not significantly different, but trended in favor of LCE treatment. Patients in the LCE group received greater L dopa dose equivalents than LC-treated patients (p < 0.001). INTERPRETATION: Initiating L-dopa therapy with LCE failed to delay the time of onset or reduce the frequency of dyskinesia compared to LC. In fact, LCE was associated with a shorter time to onset and increased frequency of dyskinesia compared to LC. These results may reflect that the treatment protocol employed did not provide continuous L-dopa availability and the higher L-dopa dose equivalents in the LCE group. PMID- 20582994 TI - Cross-resistance and possible mechanisms of chlorpyrifos resistance in Laodelphax striatellus (Fallen). AB - BACKGROUND: Laodelphax striatellus (Fallen) is a major pest of cultivated rice and is commonly controlled in China with the organophosphate insecticides. To develop a better resistance management strategy, a chlorpyrifos-resistant strain of L. striatellus was selected in the laboratory, and its cross-resistance to other insecticides and possible mechanisms of the chlorpyrifos resistance were investigated. RESULTS: After 25 generations of selection with chlorpyrifos, the selected strain of L. striatellus developed 188-fold resistance to chlorpyrifos in comparison with the susceptible strain, and showed 14- and 1.6-fold cross resistance to dichlorvos and thiamethoxam respectively. There was no apparent cross-resistance to abamectin. Chlorpyrifos was synergised by the inhibitor triphenyl phosphate; the carboxylesterase synergistic ratio was 3.8 for the selected strain, but only 0.92 for the susceptible strain. The carboxylesterase activity of the selected strain was approximately 4 times that of the susceptible strain, whereas there was no significant change in the activities of alkaline phosphatase, acid phosphatase, glutathione S-transferase and cytochrome P450 monooxygenase between the strains. The Michaelis constant of acetylcholinesterase, maximum velocity of acetylcholinesterase and median inhibitory concentration of chlorpyrifos-oxon on acetylcholinesterase were 1.7, 2.5 and 5 times higher respectively in the selected strain. CONCLUSION: The high cross-resistance to the organophosphate dichlorvos in the chlorpyrifos-resistant strain suggests that other non-organophosphate insecticides would be necessary to counter resistance, should it arise in the field. Enhanced activities of carboxylesterase and the acetylcholinesterase insensitivity appear to be important mechanisms for chlorpyrifos resistance in L. striatellus. PMID- 20582995 TI - Ageing and irradiance enhance vitamin E content in green edible tissues from crop plants. AB - BACKGROUND: Tocopherol (vitamin E) is an antioxidant essential in human nutrition. Several approaches have aimed to enhance tocopherol content in crops by the genetic modification of plants, a practice that generates some social concern. As tocopherol accumulates with leaf age in some wild plants and the antioxidant mechanisms respond with flexibility to stress conditions, it is hypothesised that tocopherol content can be increased in edible plants by the manipulation of harvesting time and growth conditions, in particular irradiance. RESULTS: Ontogenic changes in tocopherol concentration have been studied in photosynthetic tissues of edible leaves (lettuce, spinach, corn salad and dandelion) and green fruits (cucumber and pepper). In all species, tocopherol content increased with tissue age. Spinach showed the fastest rate of tocopherol accumulation, and growth at higher irradiance had a synergistic effect on the rate of accumulation. The same irradiance dependence of this accumulation was observed in fruits, but a final decrease with senescence occurred in cucumber. CONCLUSION: This study demonstrates that the content of tocopherol in vegetables can be notably enhanced (or reduced) by simply selecting the appropriate harvesting time and/or by manipulating the environmental conditions during the growth period. PMID- 20582996 TI - Nutrient use efficiency and arbuscular mycorrhizal root colonisation of winter wheat cultivars in different farming systems of the DOK long-term trial. AB - BACKGROUND: For organic farming, cultivars are required with high nutrient use efficiency under nutrient limited conditions. Arbuscular mycorrhizal fungi (AMF) are known to contribute to nutrient uptake under low input conditions. We compared nutrient use efficiency (NUE) of old and modern organically and conventionally bred cultivars in organic and conventional systems and assessed AMF-root colonisation (AMF-RC) in relation to nutrient concentrations. RESULTS: Cultivars and systems had a statistically significant effect on nitrogen (N) and phosphorus (P) concentrations and NUE parameters, whereas no genotype x environment interactions appeared. In contrast to N and P uptake, the NUE parameters were higher under organic than under conventional conditions. NUE for N increased with the year of release of cultivars. In the organic systems, the organically bred cultivars could not outperform the conventionally bred cultivars in grain yield and NUE parameters. AMF-RC was higher in the organic than in the conventional system, but did not differ among cultivars. CONCLUSION: Cultivars achieving high NUE in the organic systems were found among modern cultivars, irrespective of the breeding programme. Nutrient conditions during the breeding programme did not affect AMF-RC. No clear evidence was found that AMF symbiosis contributed more to nutrient concentrations under low input than under high input conditions. PMID- 20582998 TI - Outcome measure for stress urinary incontinence treatment (OMIT): results of two society of urodynamics and female urology (SUFU) surveys. AB - INTRODUCTION: To reach some agreement on a minimum set of outcomes measures (OMs) for the post-operative evaluation of stress incontinent women, we applied the concept of "lower common denominator" to study which OM instruments are used amongst SUFU members. METHODS: With SUFU approval, a short online, 11 items, email-based survey was prepared to assess what OMs current SUFU members are using in daily practice. The first survey administered after the annual SUFU meeting targeted recent SUFU meeting attendees. The same survey was redistributed later on to include all SUFU members. RESULTS: Each survey ran for a 10-day period. Response rate for the first survey was 50 (approximately 30%) and 106 (approximately 25%) for the second. Responders were geographically well distributed, had been in practice for 1-15 years (approximately 75%), performed 5 15 cases/month, and practiced in a university (56%) or group (30%) setting. Great consistency was noted between surveys for preferred questionnaires [UDI-6 (40 52%), UDI-6, and IIQ-7 (30-34%)], office tests [urinalysis and post-void residual (30-35%)], exam [Baden-Walker and/or POP-Q (38-55%), cough stress test (54-51%)], imaging (none), and urodynamics (none, unless complications). The most common "dislikes" in descending order were: 24 hr pad test, Q-tip test, bladder diary, long questionnaires, POP-Q. CONCLUSION: These two SUFU surveys did not explore what each physician thinks is the best OM but what members use regularly in their practices. Similar findings were noted in both surveys, supporting the concept that a minimum set of OM could be developed for reporting surgical outcomes of incontinence procedures in the future. PMID- 20582997 TI - Thalamic sensitization transforms localized pain into widespread allodynia. AB - OBJECTIVE: Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole-body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin. METHODS: Extracephalic allodynia was assessed using single unit recording of thalamic trigeminovascular neurons in rats and contrast analysis of blood oxygenation level-dependent (BOLD) signals registered in functional magnetic resonance imaging (fMRI) scans of patients exhibiting extracephalic allodynia. RESULTS: Sensory neurons in the rat posterior thalamus that were activated and sensitized by chemical stimulation of the cranial dura exhibited long-lasting hyperexcitability to innocuous (brush, pressure) and noxious (pinch, heat) stimulation of the paws. Innocuous, extracephalic skin stimuli that did not produce neuronal firing at baseline (eg, brush) became as effective as noxious stimuli (eg, pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, fMRI assessment of BOLD signals showed that brush and heat stimulation at the skin of the dorsum of the hand produced larger BOLD responses in the posterior thalamus of subjects undergoing a migraine attack with extracephalic allodynia than the corresponding responses registered when the same patients were free of migraine and allodynia. INTERPRETATION: We propose that the spreading of multimodal allodynia and hyperalgesia beyond the locus of migraine headache is mediated by sensitized thalamic neurons that process nociceptive information from the cranial meninges together with sensory information from the skin of the scalp, face, body, and limbs. PMID- 20582999 TI - Systematic review: Abdominal or pelvic floor muscle training. PMID- 20583001 TI - Real-time measurement of oxyhemoglobin concentration changes in the frontal micturition area: an fNIRS study. AB - OBJECTIVE: To explore brain activity in the frontal micturition area during natural bladder behavior. METHODS: Five control subjects (one man and four women; mean age 61 years [38-70]) and four subjects with detrusor overactivity (all men; mean age 55 years [33-65]) were enrolled in the study. We performed real-time measurements of oxyhemoglobin concentration (oxy-Hb) changes in the frontal micturition area using functional near-infrared spectroscopy (fNIRS) in response to quasi-natural, continuous bladder filling, and voiding in a sitting position. RESULTS: In the control group the following results were obtained: (1) a slight increase of oxy-Hb before first sensation occurred, (2) there was a continuous increase of oxy-Hb during bladder filling to the point just after voiding began, (3) there was a continuous decrease of oxy-Hb after voiding, (4) in subjects who were unable to urinate, oxy-Hb also decreased after attempting to void, and (5) the area activated was the bilateral lateral prefrontal area, particularly Brodmann's areas 8, 10, and 46. In the detrusor overactivity group, (6) an increase of oxy-Hb before first sensation was rare and frontal cortical activation was weak, (7) at the moment detrusor overactivity appeared, fNIRS brain activity in the frontal cortex did not change significantly; and otherwise the results were almost the same as those in the control group. CONCLUSIONS: This study shows that the frontal micturition area is activated during natural bladder filling and voiding using fNIRS. PMID- 20583009 TI - Cancer and neurodegeneration meet. PMID- 20583010 TI - Whole blood assay for trypsin activity using polyanionic focusing gel electrophoresis. AB - The measurement of trypsin activity directly in blood is important for the development of novel diagnostics and for biomedical research. Presently, most degradative enzyme assays require sample preparation, making them time consuming, costly, and less accurate. We recently demonstrated a simple and rapid electrophoretic assay for the measurement of trypsin activity directly in whole blood. This assay utilizes a charge-changing fluorescent peptide substrate that produces a positively charged fluorescent product fragment upon cleavage by the target enzyme. This fragment is then rapidly separated from whole blood by electrophoresis and quantified with a fluorescent detector. In this study, we demonstrate that polyanionic poly-L-glutamic acid-doped polyacrylamide gels can focus the fluorescent cleavage product and markedly improve the LODs of the assay. A LOD of 2 pg in 6 microL (0.3 ng/mL) in whole human blood was achieved after a 1-h reaction of enzyme and substrate followed by 10 min of electrophoresis. This is 50- to 200-fold better than the estimated reference levels for trypsin (15-60 ng/mL) in blood. This straightforward technique now allows for the rapid measurement of clinically relevant levels of trypsin activity in microliter volumes of whole blood, providing a useful tool for the development of novel point-of-care diagnostics. PMID- 20583011 TI - Chemometric and biological validation of a capillary electrophoresis metabolomic experiment of Schistosoma mansoni infection in mice. AB - Metabonomic and metabolomic studies are increasingly utilized for biomarker identification in different fields, including biology of infection. The confluence of improved analytical platforms and the availability of powerful multivariate analysis software have rendered the multiparameter profiles generated by these omics platforms a user-friendly alternative to the established analysis methods where the quality and practice of a procedure is well defined. However, unlike traditional assays, validation methods for these new multivariate profiling tools have yet to be established. We propose a validation for models obtained by CE fingerprinting of urine from mice infected with the blood fluke Schistosoma mansoni. We have analysed urine samples from two sets of mice infected in an inter-laboratory experiment where different infection methods and animal husbandry procedures were employed in order to establish the core biological response to a S. mansoni infection. CE data were analysed using principal component analysis. Validation of the scores consisted of permutation scrambling (100 repetitions) and a manual validation method, using a third of the samples (not included in the model) as a test or prediction set. The validation yielded 100% specificity and 100% sensitivity, demonstrating the robustness of these models with respect to deciphering metabolic perturbations in the mouse due to a S. mansoni infection. A total of 20 metabolites across the two experiments were identified that significantly discriminated between S. mansoni-infected and noninfected control samples. Only one of these metabolites, allantoin, was identified as manifesting different behaviour in the two experiments. This study shows the reproducibility of CE-based metabolic profiling methods for disease characterization and screening and highlights the importance of much needed validation strategies in the emerging field of metabolomics. PMID- 20583012 TI - Cyclative cleavage through dipolar cycloaddition: polymer-bound azidopeptidylphosphoranes deliver locked cis-triazolylcyclopeptides as privileged protein binders. PMID- 20583014 TI - Beyond the Pummerer reaction: recent developments in thionium ion chemistry. AB - Since the early 1960s the Pummerer reaction has evolved to become an indispensable tool for synthesis, and continues to serve as a source of inspiration for organic chemists. In recent years, many exciting advances have demonstrated the broad scope and synthetic utility of Pummerer methodology and the versatility of thionium ion intermediates. PMID- 20583013 TI - Modular synthesis of 1,2-diamine derivatives by palladium-catalyzed aerobic oxidative cyclization of allylic sulfamides. PMID- 20583015 TI - RNA dynamics by design: biasing ensembles towards the ligand-bound state. PMID- 20583016 TI - A metal-organic framework as an electrocatalyst for ethanol oxidation. PMID- 20583017 TI - Fused-gene approach to photoswitchable and fluorescent biliproteins. PMID- 20583018 TI - Uniform amplification of phage with different growth characteristics in individual compartments consisting of monodisperse droplets. PMID- 20583019 TI - The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5 methoxycarbonylmethyluridine at the wobble position of tRNA. PMID- 20583020 TI - Porous metal carboxylate boron imidazolate frameworks. PMID- 20583021 TI - Quantification of the sixth DNA base hydroxymethylcytosine in the brain. PMID- 20583022 TI - Amidinium carboxylate salt bridges as a recognition motif for mechanically interlocked molecules: synthesis of an optically active [2]catenane and control of its structure. PMID- 20583023 TI - Total synthesis and structural reassignment of (+)-dictyosphaeric acid A: a tandem intramolecular Michael addition/alkene migration approach. PMID- 20583024 TI - The first artificial cell--a revolutionary step in synthetic biology? PMID- 20583025 TI - Glycosylation enhances peptide hydrophobic collapse by impairing solvation. AB - Post-translational N-glycosylation of proteins is ubiquitous in eukaryotic cells, and has been shown to influence the thermodynamics of protein collapse and folding. However, the mechanism for this influence is not well understood. All atom molecular dynamics simulations are carried out to study the collapse of a peptide linked to a single N-glycan. The glycan is shown to perturb the local water hydrogen-bonding network, rendering it less able to solvate the peptide and thus enhancing the hydrophobic contribution to the free energy of collapse. The enhancement of the hydrophobic collapse compensates for the weakened entropic coiling due to the bulky glycan chain and leads to a stronger burial of hydrophobic surface, presumably enhancing folding. This conclusion is reinforced by comparison with coarse-grained simulations, which contain no explicit solvent and correspondingly exhibit no significant thermodynamic changes on glycosylation. PMID- 20583029 TI - IL-6: regulator of Treg/Th17 balance. AB - IL-6 is a pleiotropic cytokine involved in the physiology of virtually every organ system. Recent studies have demonstrated that IL-6 has a very important role in regulating the balance between IL-17-producing Th17 cells and regulatory T cells (Treg). The two T-cell subsets play prominent roles in immune functions: Th17 cell is a key player in the pathogenesis of autoimmune diseases and protection against bacterial infections, while Treg functions to restrain excessive effector T-cell responses. IL-6 induces the development of Th17 cells from naive T cells together with TGF-beta; in contrast, IL-6 inhibits TGF-beta induced Treg differentiation. Dysregulation or overproduction of IL-6 leads to autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA), in which Th17 cells are considered to be the primary cause of pathology. Given the critical role of IL-6 in altering the balance between Treg and Th17 cells, controlling IL-6 activities is potentially an effective approach in the treatment of various autoimmune and inflammatory diseases. Here, we review the role of IL-6 in regulating Th17/Treg balance and describe the critical functions of IL-6 and Th17 in immunity and immune-pathology. PMID- 20583030 TI - Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. AB - Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and many other stimuli, including products derived from either pathogens or the host during innate immune responses. Although mast cells are best known for their role in IgE-associated allergic disorders, mast cells can also exacerbate models of autoimmunity, enhance the sensitization and/or effector phases of certain cutaneous contact hypersensitivity responses, and increase inflammation and mortality during some severe bacterial infections. In other settings, however, mast cells can limit inflammation and tissue injury: mast cells promote host resistance in certain models of bacterial or parasite infection, limit pathology during some acquired immune responses to environmental Ag, including examples of severe contact hypersensitivity, and have adjuvant-like properties that can enhance the development of protective immunity against pathogens. These and other findings suggest that mast cells occupy a critical niche at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may function to perturb or help to restore homeostasis (or both), with consequences that can either promote health or contribute to disease. PMID- 20583034 TI - Multi-photon resonance enhancement of third harmonic generation in human oxyhemoglobin and deoxyhemoglobin. AB - Cancer cells require excessive oxygen and nutrition to support their rapid growth, so angiogenesis and decrease of blood oxygen are often associated with areas of cancer development. Current technologies for blood oxygen measurement, however, do not possess high spatial resolution and therefore cannot be used to detect small tumors in their early stage. In this paper, we studied the third harmonic generation (THG) spectra of oxy- and deoxyhemoglobin in the 1170-1365 nm region, which is strongly influenced by the multi-photon resonance effect, especially around the Soret transition band. Our spectroscopic results thus indicate the high potential of THG spectroscopic microscopy for oxygen depletion level measurement of a single red blood cell in vivo. PMID- 20583031 TI - NKT cells, Treg, and their interactions in bone marrow transplantation. AB - Bone marrow transplantation (BMT) is a potentially curative treatment for patients with leukemia and lymphoma. Tumor eradication is promoted by the anti tumor activity of donor T cells contained in the transplant; however, donor T cells also mediate the serious side effect of graft-versus-host disease (GVHD). Separation of GVHD from graft anti-tumor activity is an important goal of research in improving transplant outcome. One approach is to take advantage of the immunomodulatory activity of regulatory NKT cells and CD4(+)CD25(+) Treg of host and/or donor origin. Both host and donor NKT cells and donor Treg are able to prevent GVHD in murine models. In this review, we summarize the mechanisms of NKT cell- and Treg-mediated protection against GVHD in mice while maintaining graft anti-tumor activity. In addition, we also examine the interactions between NKT cells and Treg in the context of BMT, and integrate the data from murine experimental models with the observations made in humans. PMID- 20583035 TI - Application of dynamic diffractive optics for enhanced femtosecond laser based cell transfection. AB - We demonstrate the advantages of a dynamic diffractive optical element, namely a spatial light modulator (SLM) for the controlled and enhanced optoinjection and phototransfection of mammalian cells with a femtosecond light source. The SLM provides full control over the lateral and axial positioning of the beam with sub micron precision. Fast beam translation enables time-sequenced irradiation, which is shown to enhance the optoinjection efficiency and alleviate the problem of exact beam positioning on the cell membrane. We show that irradiation in three axial positions doubles the number of viably optoinjected cells when compared with a single dose. The presented system also enables untargeted raster scan irradiation which provides a higher throughput transfection of adherent cells at the rate of 1 cell per second. Additionally, fluorescent imaging is used to demonstrate cell selective two-step gene therapy. PMID- 20583036 TI - Improved film morphology reduces charge carrier recombination into the triplet excited state in a small bandgap polymer-fullerene photovoltaic cell. PMID- 20583037 TI - Capsules with silver nanoparticle enrichment subdomains and their antimicrobial properties. AB - The fabrication of polyelectrolyte multilayer capsules with controllable submicron-sized subdomains and the in situ synthesis of silver nanoparticles are reported. Because poly(acrylic acid) (PAA) is released from the shell of the capsules in the dissolution process of sacrificial cores, the remaining poly(4 vinylpyridine) (PVP) forms subdomains of spheres with controllable sizes, which can be tuned by the number of PVP/PAA bilayers. This creates capsules with special surface morphology and enables the in situ synthesis of Ag nanoparticles within the PVP subdomains on the shell of capsules. In addition, the in-situ formed Ag nanoparticles can be mostly released from PVP subdomains of capsules in pH 2.0 solution, whereas they are stable in neutral solution. These specially designed capsules containing Ag nanoparticles can be used as antimicrobial materials and potentially benefit remote drug release by laser activation. PMID- 20583038 TI - Organic fluorophores exhibiting highly efficient photoluminescence in the solid state. AB - There has been extensive research on the development of organic optoelectronic devices, such as organic light-emitting diodes, organic field-effect transistors, and organic solid-state lasers from various viewpoints, ranging from basic studies to practical applications. As organic materials are used as solids in these devices, the importance of organic chromophores that exhibit intense emissions of visible light in the solid state is greatly increasing in the field of organic electronics. However, highly efficient emission from organic solids is very difficult to attain because most organic emitting materials strongly tend to cause concentration quenching of the luminescence in the condensed phase. Therefore, in order to generate and improve organic optoelectronic devices, it is necessary to design novel chromophores that exhibit superior solid-state emission performance. This Focus Review covers the recent development of highly emissive organic small molecules whose photoluminescence quantum yields in the solid state have been reported. Following the introduction, the photophysical processes of excited molecules are briefly reviewed. Subsequently, organic solid fluorophores are described with an emphasis on the characteristics of their molecular structures. PMID- 20583039 TI - One-dimensional carbon nanotube/SnO2/noble metal nanoparticle hybrid nanostructure: synthesis, characterization, and electrochemical sensing. AB - Herein we report a facile and efficient method for self-assembling noble-metal nanoparticles (NPs) to the surface of SnO(2)-coated carbon nanotubes (CNT@SnO(2)) to construct CNT@SnO(2)/noble metal NP hybrids. By using SnCl(4) as the precursor of the SnO(2) shell on the surface of CNTs, the hydrolysis speed of SnCl(4) was slowed down in ethanol containing a trace amount of urea and water. The coaxial nanostructure of CNT@SnO(2) was confirmed by using X-ray powder diffraction (XRD) and transmission electron microscopy (TEM). It was found that the coating layer of SnO(2) was homogeneous with the mean thickness of 8 nm. The CNT@SnO(2)/noble metal NP hybrids were obtained by mixing noble-metal NPs with as-prepared CNT@SnO(2) coaxial nanocables by means of a self-assembly strategy. With the amino group terminated, the CNT@SnO(2) coaxial nanocable can readily adsorb the as-prepared noble-metal NPs (Au, Ag, Au-Pt, and Au-Pd NPs). The presence of an amino group at the surface of SnO(2) was proved by use of X-ray photoelectron spectroscopy (XPS). In addition, H(2)O(2) sensing by amperometric methods could serve as detection models for investigating the electrocatalytic ability of as prepared hybrid materials. It was found that wide linear ranges and low detection limits were obtained by using the enzyme-free CNT@SnO(2)@Au-Pt modified electrode, which indicated the potential utilizations of the hybrid based on CNT@SnO(2) for electrochemical sensing. PMID- 20583040 TI - A dendrimer chiroptical switch based on the reversible intramolecular photoreaction of anthracene and benzene rings. AB - A series of Frechet-type dendrimers with 9-benzyloxymethylanthracene cores were synthesized and characterized. The chiral source for the dendrimers was an (S)-2 methyl-1-butoxy group in the 3-position of the benzene ring. Irradiation at 366 nm of a dilute benzene solution led to the formation of two diastereomers (1:1) through a quantitative intramolecular [4pi+4pi] cycloaddition between the central anthracene ring and the neighboring benzene ring. The process can be reversed with 254 nm UV light or heat. The benzene rings in the dendrons work as a light harvesting system. The optical rotation values measured for the reversible process showed fatigue resistance. Thus, a promising new type of chiroptical switch has been created that has optical rotation values as output signals. PMID- 20583041 TI - A pre-organised truxene platform for phosphorescent [Ru(bpy)2] and [Os(bpy)2] metal centres: a clear-cut switch from Forster- to Dexter-type energy-transfer mechanism. AB - We report on the synthesis, optical properties and energy-transfer features of a series of transition-metal-containing complexes and dyads, based on a pre organised truxene scaffold. In this series, the [Ru(bpy)(3)](2+) and [Os(bpy)(3)](2+) photoactive terminals are coupled to the bridging aromatic truxene core through rigid ethynyl linkers. The photoinduced energy-transfer processes taking place from the Ru- to the Os-based levels, and from the truxene bridging ligand to the terminal-metal chromophores are studied and the pathways and mechanisms are discussed. The photoinduced energy-transfer process observed in the dyad proceeds rapidly through: i) an efficient (1)L-->(1)Os direct energy transfer followed by intersystem crossing to (3)Os, and ii) a fast (1)L-->(1)Ru energy-transfer step and subsequent intersystem crossing to (3)Ru followed by a (3)Ru-->(3)Os energy-transfer process. The first (1)L-->(1)Os and (1)L-->(1)Ru steps are controlled by a dipole-dipole interaction (Forster mechanism), whereas the subsequent (3)Ru-->(3)Os step proceeds by means of a long-range (approximately 24 A) through-bond mediated Dexter mechanism, facilitated by the conjugation along the bpy-truxene-bpy molecular axis. PMID- 20583042 TI - Cavity-shaped ligands: calix[4]arene-based monophosphanes for fast Suzuki-Miyaura cross-coupling. AB - Five conical calix[4]arenes that have a PPh(2) group as the sole functional group anchored at their upper rim were assessed in palladium-catalysed cross-coupling reactions of phenylboronic acid with aryl halides (dioxane, 100 degrees C, NaH). With arylbromides, remarkably high activities were obtained with the catalytic systems remaining stable for several days. The performance of the ligands is comparable to a Buchwald-type triarylphosphane, namely, (2'-methyl[1,1'-biphenyl] 2-yl)diphenylphosphane, which in contrast to the calixarenyl phosphanes tested may display chelating behaviour in solution. With the fastest ligand, 5 diphenylphosphanyl-25,26,27,28-tetra(p-methoxy)benzyloxy-calix[4]arene (8), the reaction turnover frequency for the arylation of 4-bromotoluene was 321,000 versus 214,000 mol(ArBr).mol(Pd)(-1).h(-1) for the reference ligand. The calixarene ligands were also efficient in Suzuki cross-coupling reactions with aryl chlorides. Thus, by using 1 mol% of [Pd(OAc)(2)] associated with one of the phosphanes, full conversion of the deactivated arenes 4-chloroanisole and 4 chlorotoluene was observed after 16 h. The high performance of the calixarenyl phosphanes in Suzuki-Miyaura coupling of aryl bromides possibly relies on their ability to stabilise a monoligand [Pd(0)L(ArBr)] species through supramolecular binding of the Pd-bound arene inside the calixarene cavity. PMID- 20583043 TI - Catalyst versus substrate induced selectivity: kinetic resolution by palladacycle catalyzed allylic imidate rearrangements. PMID- 20583044 TI - Identifying the bond responsible for the fluorescence modulation in an amyloid fibril sensor. AB - An ultrafast intramolecular bond twisting process is known to be the responsible mechanism for the sensing activity of the extensively used amyloid fibril sensor thioflavin T (ThT). However, it is not yet known which one of the two possible single bonds in ThT is actually involved in the twisting process. To resolve this fundamental issue, two derivatives of ThT have been designed and synthesized and subsequently their photophysical properties have been studied in different solvents. It is understood from the present study that the rotation around the central C-C single bond, and not that around the C-N single bond, is primarily responsible for the sensor activity of ThT. Detailed viscosity-dependent fluorescence studies revealed that the ThT derivative with restricted C-N bond rotation acts as a better sensor than the derivative with free C-N bond rotation. The better sensory activity is directly correlated with a shorter excited-state lifetime. Results obtained from the photophysical studies of the ThT derivatives have also been supported by the results obtained from quantum chemical calculations. PMID- 20583045 TI - Magnetic coupling in enantiomerically pure trinuclear helicate-type complexes formed by hierarchical self-assembly. AB - Based on chiral, enantiomerically pure 7-[(S)-phenylethylurea]-8-hydroxyquinoline (1-H), trinuclear helicate-type complexes 2-5 are formed with divalent transition metal cations. X-ray structural analyses reveal the connection of two monomeric complex units [M(1)(3)](-) (M=Zn, Mn, Co, Ni) by a central metal ion to form a "dimer". Due to the enantiopurity of the ligand, the complexes are obtained as pure enantiomers, resulting in pronounced circular dichroism (CD) spectra. Single ion effects and intra- and intermolecular coupling are observed with dominating ferromagnetic coupling in the case of the cobalt(II) and nickel(II) and dominating antiferromagnetic coupling in the case of the manganese(II) complex. PMID- 20583046 TI - Cyclodextrin-based bimodal fluorescence/MRI contrast agents: an efficient approach to cellular imaging. AB - A novel bimodal fluorescence/MRI probe based on a cyclodextrin scaffold has been synthesized and characterized. The final agent employs the fluorescein (F) functionality as a fluorescence marker and the Gd(III) complex of a macrocyclic DOTA-based ligand (GdL) having one aminobenzyl-phosphinic acid pendant arm as an MRI probe, and has a statistical composition of (GdL)(6.9)-F(0.1)-beta-CD. Slow rotational dynamics (governed by a very rigid cyclodextrin scaffold) combined with fast water exchange (ensured by the chosen macrocyclic ligand) resulted in a high relaxivity of approximately 22 s(-1) mM(-1) per Gd(III) or approximately 150 s(-1) mM(-1) per molecule of the final conjugate (20 MHz, 25 degrees C). In vitro labelling of pancreatic islets (PIs) and rat mesenchymal stem cells has been successfully performed. The agent is not cytotoxic and is easily internalized into cells. The labelled cells can be visualized by MRI, as proved by the detection of individual labelled PIs. A fluorescence study performed on mesenchymal stem cells showed that the agent stays in the intracellular space for a long time. PMID- 20583047 TI - Towards molecular design rationalization in branched multi-thiophene semiconductors: the 2-thienyl-persubstituted alpha-oligothiophenes. AB - The introduction of branching in multi-thiophene semiconductors, although granting the required solubility for processing, results in an increased molecular fluxionality and a higher level of distortion, thus hampering pi conjugation. Accordingly, branched oligothiophenes require rationalization of their structure-reactivity relationships for target-oriented design and optimization of the synthetic effort. Our current research on spiderlike oligothiophenes affords deep insight into the subject, and introduces new, easily accessible molecules with attractive functional properties. In particular, a regular series, T'X(Y), of five new multi-thiophene systems, T'5(3), T'8(4), T'11(5), T'14(6), and T'17(7), constituted by five, eight, 11, 14, and 17 thiophene units, respectively, their longest alpha-conjugated chain consisting of tri-, tetra-, penta-, hexa-, and heptathiophene moieties, respectively, has been synthesized and fully characterized from the structural, spectroscopic, and electrochemical point of view. The electronic properties of the monomers and their electropolymerization ability are discussed and rationalized as a function of their molecular structure, particularly in comparison with the series of 5 (2,2'-dithiophene)yl-persubstituted alpha-oligothiophenes (TX(Y)) previously reported by us. These oligothiophenes are easily accessible materials, with promising properties for applications as active layers in multifunctional organic devices including solar cells. PMID- 20583048 TI - Seed-mediated synthesis of Au nanocages and their electrocatalytic activity towards glucose oxidation. AB - We report a modified seed-mediated approach for the synthesis of uniform Au nanocages (AuNCs). HAuCl(4) was reduced in an aqueous mixture of hexamethylenetetramine (HMT), poly(N-vinyl-2-pyrrolidone) (PVP), and AgNO(3). The nanocages were (54.6+/-13.3) nm in outer-edge length and about 12 nm in wall thickness. The structure of the AuNCs was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Morphological changes associated with the seed-mediated growth of Au nanoparticles (AuNPs) in the absence of HMT or PVP were examined. The results demonstrate that both PVP and HMT play important roles in the formation of the nanocage structure. The function of AgNO(3) was also studied. A possible formation mechanism for the AuNCs was investigated by monitoring TEM images of the Au nanostructures formed at various reaction times. The electrocatalytic activity of the AuNCs towards the oxidation of glucose was explored, and a nonenzymatic glucose sensor with high sensitivity and good stability was further fabricated. To the best of our knowledge, this is the first report of the preparation of AuNCs by a seed-mediated strategy and of the application of AuNCs in the electrocatalytic oxidation of glucose. Our results should facilitate the creation of novel nanomaterials with various morphologies and the exploration of their applications in nanotechnological, optical, catalytic, and materials science fields. PMID- 20583049 TI - Two-step thermal spin transition and LIESST relaxation of the polymeric spin crossover compounds Fe(X-py)2[Ag(CN)2]2 (X=H, 3-methyl, 4-methyl, 3,4-dimethyl, 3 Cl). AB - In the series of polymeric spin-crossover compounds Fe(X-py)(2)[Ag(CN)(2))](2) (py=pyridine, X=H, 3-Cl, 3-methyl, 4-methyl, 3,4-dimethyl), magnetic and calorimetric measurements have revealed that the conversion from the high-spin (HS) to the low-spin (LS) state occurs by two-step transitions for three out of five members of the family (X=H, 4-methyl, and X=3,4-dimethyl). The two other compounds (X=3-Cl and 3-methyl) show respectively an incomplete spin transition and no transition at all, the latter remaining in the HS state in the whole temperature range. The spin-crossover behaviour of the compound undergoing two step transitions is well described by a thermodynamic model that considers both steps. Calculations with this model show low cooperativity in this type of systems. Reflectivity and photomagnetic experiments reveal that all of the compounds except that with X=3-methyl undergo light-induced excited spin state trapping (LIESST) at low temperatures. Isothermal HS-to-LS relaxation curves at different temperatures support the low-cooperativity character by following an exponential decay law, although in the thermally activated regime and for aX=H and X=3,4-dimethyl the behaviour is well described by a double exponential function in accordance with the two-step thermal spin transition. The thermodynamic parameters determined from this isothermal analysis were used for simulation of thermal relaxation curves, which nicely reproduce the experimental data. PMID- 20583050 TI - Triptycene-derived calix[6]arenes: synthesis, structures, and their complexation with fullerenes C60 and C70. AB - Two pairs of novel triptycene-derived calix[6]arenes 4a,b and 5a,b have been efficiently synthesized through both one-pot and two-step fragment-coupling strategies starting from 2,7-bis(hydroxymethyl)-1,8-dimethoxytriptycene 1. Subsequent demethylation of 4a,b and 5a,b with BBr(3) in dry dichloromethane gave the macrocyclic compounds 6a,b and 7a,b. Treatment of either 4a or 6a with AlCl(3) resulted in the same debutylated product 8, while 9 was similarly obtained from either 5a or 7a. Structural studies revealed that all of the macrocycles have well-defined structures with fixed conformations both in solution and in the solid state owing to the introduction of the triptycene moiety with a rigid three-dimensional (3D) structure, making them very different from their classical calix[6]arene counterparts. As a consequence, it was found that all of these the triptycene-derived calix[6]arenes could encapsulate small neutral molecules in their cavities in the solid state. Moreover, it was also found that the macrocycles 4b and 5b showed highly efficient complexation abilities toward fullerenes C(60) and C(70), forming 1:1 complexes with association constants ranging from (5.22+/-0.20) x 10(4) to (8.68+/-0.30) x 10(4) M(-1). PMID- 20583051 TI - Thermo- and acid-responsive photochromic spironaphthoxazine-containing organogelators. AB - A series of photochromic spironaphthoxazine derivatives has been designed, synthesized, and characterized by using (1)H NMR spectroscopy, FAB mass spectrometry, and elemental analysis. Their photophysical and photochromic behavior have been investigated. Two of the compounds (G(12)-en-SA-SO and G(16) en-SA-SO) have been shown to be capable of forming stable thermoreversible organogels in organic solvents, tested by the "stable-to-inversion of a test tube" method. Addition of p-toluenesulfonic acid was found to induce the formation of stable organogels at concentrations below that of the critical gelation concentration (c.g.c.), with a concomitant change in color from colorless to purple. Transmission electron microscopy and scanning electron microscopy of the xerogels showed typical fibrous structures in the micrometer scale. The activation parameters for the bleaching reaction of G(8)-en-SA-SO in the solution state and G(16)-en-SA-SO in the gel state have been determined in ethanol through kinetic studies at various temperatures. The results showed that the rate of the bleaching reaction in the gel state was much slower than that in the solution state. PMID- 20583052 TI - Planar chiral organoborane Lewis acids derived from naphthylferrocene. AB - Enantiomerically pure metalated 2-(1-naphthyl)ferrocene (NpFc) derivatives NpFcM (M=SnMe(3), HgCl) were prepared and characterized by multinuclear NMR and UV/Vis spectroscopy, cyclic voltammetry, and elemental analysis. Optical rotation measurements were performed and the absolute configuration of the new planar chiral ferrocene species was confirmed by single-crystal X-ray diffraction analysis. The mercuriated species NpFcHgCl proved suitable as a reagent for the preparation of the chiral organoborane Lewis acid NpFcBCl(2), which can in turn be converted to other ferrocenylboranes by replacement of Cl with nucleophiles. The highly Lewis acidic perfluoroarylborane derivatives NpFcB(C(6)F(5))Cl and NpFcB(C(6)F(5))(2) were successfully prepared by treatment with CuC(6)F(5). The structures were studied by single-crystal X-ray diffraction and variable temperature (19)F NMR spectroscopy, which suggested that pi stacking of a C(6)F(5) group on boron with the adjacent naphthyl group is energetically favorable. UV/Vis absorption spectroscopy and cyclic voltammetry measurements were performed to examine the electronic properties of these novel redox-active chiral Lewis acids. PMID- 20583053 TI - 2-Hydroxyazobenzenes to tailor pH pulses and oscillations with light. AB - This paper evaluates the 2-hydroxyazobenzene platform for tailoring proton concentration pulses and oscillations with monochromatic light. The easily prepared 2-hydroxyazobenzenes exhibit large absorptions in the near-UV range. Photoisomerization was investigated by UV/Vis absorption, (1)H NMR spectroscopy, and steady-state fluorescence emission. In the whole investigated series, the trans stereoisomer of the 2-hydroxyazobenzene motif provides the corresponding cis derivative with an action cross section in the 10(3) M(-1) cm(-1) range. At the same time, photoisomerization is accompanied by a significant pK drop of the phenol group. According to the phenyl-substituent pattern, cis-to-trans thermal back-isomerization can be tuned in the 10 ms-100 s range. Up to 2 units of reversible pH drops or pH oscillations on the 10 s timescale have been obtained by appropriately tailoring single-wavelength illumination of 2-hydroxyazobenzene solutions. PMID- 20583054 TI - Synthesis of functionalized indoles with a trifluoromethyl-substituted stereogenic tertiary carbon atom through an enantioselective Friedel-Crafts alkylation with beta-trifluoromethyl-alpha,beta-enones. AB - Chiral complexes of BINOL-based ligands with zirconium tert-butoxide catalyze the Friedel-Crafts alkylation reaction of indoles with beta-trifluoromethyl alpha,beta-unsaturated ketones to give functionalized indoles with an asymmetric tertiary carbon center attached to a trifluoromethyl group. The reaction can be applied to a large number of substituted alpha-trifluoromethyl enones and substituted indoles. The expected products were obtained with good yields and ees of up to 99%. PMID- 20583055 TI - Mechanistic insights into the one-pot synthesis of propargylamines from terminal alkynes and amines in chlorinated solvents catalyzed by gold compounds and nanoparticles. AB - Propargylamines can be obtained from secondary amines and terminal alkynes in chlorinated solvents by a three- and two-component synthesis catalyzed by gold compounds and nanoparticles (Au-NP) under mild conditions. The use of dichloromethane allows for the activation of two C-Cl bonds and a clean transfer of the methylene fragment to the final product. The scope of the reaction as well as the influence of different gold(III) cycloaurated complexes and salts has been investigated. The involvement of gold nanoparticles generated in situ in the process is discussed and a plausible reaction mechanism is proposed on the basis of the data obtained. PMID- 20583056 TI - Formation and rearrangement of Sn(II) phosphanediide cages. AB - The room-temperature reactions of Sn(NMe(2))(2) with less sterically demanding primary phosphines (RPH(2)) give the homoleptic phosphanediide compounds [SnPR](n) in high yields (R=tBu (1a), cyclohexyl (1b), 1-adamantyl (1c)). However, the room-temperature reaction of Mes*PH(2) (Mes*=2,4,6-tBu(3)C(6)H(2)) with Sn(NMe(2))(2) gives the model intermediate [{SnPMes*}(2)(mu NMe(2))SnP(H)Mes*] (3), together with the product of complete deprotonation [SnPMes*](3) (4). Phosphorus--phosphorus bonded products are produced in these reactions at elevated temperatures. If the reaction producing 1a is heated to reflux then [tBuP(H)P(H)tBu] is produced as the major product (together with tin metal). The novel octanuclear cage [{SnPtBu}(7)Sn(PtBu)(3)] (2) can also be isolated in low yield, resulting from formal addition of the heterocyclic stannylene [(tBuP)(3)Sn] to a Sn-P single bond of the intact structure of 1a. Prolonged heating of the reaction producing 3 and 4 leads to the formation of the diphosphene [PMes*](2) (5) and tin metal. The X-ray structures of the heptamer 1a (n=7), octanuclear 2 and trinuclear 3 are reported. PMID- 20583057 TI - A computational study of rhodium pincer complexes with classical and nonclassical hydride centres as catalysts for the hydroamination of ethylene with ammonia. AB - The catalytic hydroamination of ethylene with ammonia was investigated by means of density functional theory (DFT) calculations. An initial computational screening of key reaction steps (C-N bond formation, N-H bond cleavage), which are assumed to be part of a catalytic cycle, was carried out for complexes with the [M(L)]-complex fragment (M=Rh, Ir; L=NCN, PCP; NCN=2,5 bis(dimethylaminomethyl)benzene, PCP=2,5-bis- (dimethylphosphanylmethyl)benzene). Based on the evaluation of activation barriers, this screening showed the rhodium compound with the NCN ligand to be the most promising catalyst system. A detailed investigation was carried out starting with the hypothetical catalyst precursor [Rh(NCN)(H)(2)(H(2))] (1). A variety of activation pathways to yield the catalytically active species [Rh(NCN)(H)(NH(2))] (5), as well as [Rh(NCN)(C(2)H(5))(NH(2))] (17), were identified. With 5 and 17 several closed catalytic cycles could be calculated. One of the calculated cycles is favoured kinetically and bond-forming events have activation barriers low enough to be put into practice. The calculations also show that for experimental realisation the synthesis of 1 is not necessary, as the synthesis of 17 would establish an active catalyst directly without the need for activation. Oligomerisation of ethylene would be possible in principle and would be expected as a competitive side reaction. Accordingly not only ethylamine would be observed in an experimental system, as amines with longer carbon chains also can be formed. PMID- 20583058 TI - Fabrication of a biocompatible and conductive platform based on a single-stranded DNA/graphene nanocomposite for direct electrochemistry and electrocatalysis. AB - A novel electrochemical platform was designed by combining the biocompatibility of single-stranded DNA (ss-DNA) and the excellent conductivity of graphene (GP). This nanocomposite (denoted as ss-DNA/GP) was first used as an electrode material for the immobilization and biosensing of redox enzymes. On the basis of electrostatic interactions, horseradish peroxidase (HRP) self-assembled with ss DNA/GP on the surface of a glassy carbon (GC) electrode to form an HRP/ss DNA/GP/GC electrode. UV/Vis and FTIR spectra were used to monitor the assembly process and indicated that the immobilized HRP on the ss-DNA/GP matrix retained its native structure well. A pair of stable and well-defined redox peaks of HRP with a formal potential of about -0.26 V (vs. Ag/AgCl) in a pH 7.0 phosphate buffer solution were obtained at the HRP/ss-DNA/GP/GC electrode; this demonstrates direct electron transfer between the immobilized HRP and the electrode. In addition, the modified electrode showed good electrocatalytic performance towards H(2)O(2) with high sensitivity, wide linear range, and good stability. Accordingly, the ss-DNA/GP nanocomposite provides a novel and efficient platform for the immobilized redox enzyme to realize direct electrochemistry and has a promising application in the fabrication of third generation electrochemical biosensors. PMID- 20583059 TI - Self-sorted assembly in a mixture of donor and acceptor chromophores. AB - A simple and novel supramolecular approach for orthogonal self-assembly of donor and acceptor chromophores has been demonstrated. Suitably designed 1,5 dialkoxynaphthalene (DAN) and naphthalene tetracarboxylic acid diimide (NDI) derivatives were used as the donor and acceptor systems, respectively. The molecular design for self-sorting relies upon the precise control over the placement of the self-complementary hydrogen-bonding units (amide functionality) with respect to the individual chromophore. By design, the distances between the two amide groups in the donor and acceptor chromophores are not identical, and consequently the effect of the hydrogen-bonding interaction cannot be maximised in the case of alternate donor-acceptor-type pi-stacking. Thus a relatively weak charge-transfer interaction is expected to be sacrificed, and segregated assembly among the individual chromophores should be enforced by virtue of the much stronger effects of hydrogen bonding and pi-pi stacking. Detailed spectroscopic studies were carried out to probe the mode of self-assembly in various derivatives of the DAN-NDI donor-acceptor pairs to establish the utility of the molecular design as a generalised one for orthogonal self-assembly. PMID- 20583060 TI - Dumbbell-shaped dinuclear iridium complexes and their application to light emitting electrochemical cells. AB - A novel family of dumbbell-shaped dinuclear complexes in which an oligophenyleneethynylene spacer is linked to two heteroleptic iridium(III) complexes is presented. The synthesis, as well as the electrochemical and photophysical characterization of the new complexes, is reported. The experimental results are interpreted with the help of density functional theory calculations. From these studies we conclude that the lowest triplet excited state corresponds to a (3)pi-pi* state located on the conjugated spacer. The presence of this state below the (3)MLCT/(3)LLCT emitting states of the end capping Ir(III) complexes explains the low quantum yields observed for the dinuclear complexes (one order-of-magnitude less) with respect to the mononuclear complexes. The potential application of the novel dinuclear complexes in optoelectronic devices has been tested by using them as the primary active component in double-layer light-emitting electrochemical cells (LECs). Although the luminance levels are low, the external quantum efficiency suggests that a near-quantitative internal electron-to-photon conversion occurs in the device. This indicates that the emission inside the device is highly optimized and that the self-quenching associated with the high concentration of the complex in the active layer is minimized. PMID- 20583061 TI - Iron(III)-catalyzed cyclization of alkynyl aldehyde acetals: experimental and computational studies. AB - FeCl(3)6 H(2)O- and FeBr(3)-catalyzed Prins cyclization/halogenation of alkynyl aldehyde acetals has been realized with acetyl chloride or bromide as halogen source in dichloromethane to afford 2-(1-halobenzylidene or alkylidene) substituted five-membered carbo- and heterocycles, and thus provides an alternative route for vinylic C-Cl and C-Br bond formation. Five- to eight membered cyclic enones were efficiently synthesized by FeCl(3)6.H(2)O-catalyzed intramolecular cyclization of alkynyl aldehyde acetals in acetone under mild conditions. An oxocarbonium species generated in situ is proposed to initiate the reaction, and the target products are formed via vinylogous carbenium cation and oxete intermediates according to DFT calculations. Intermolecular reactions of alkynes and aldehyde acetals were also investigated with 20-40 mol% FeCl(3)6.H(2)O catalyst, and produced alpha,beta-unsaturated enones and chlorinated indene derivatives. The present protocol has applications in the synthesis of carbo-, oxa- and azacycles. PMID- 20583062 TI - Straightforward generation of helical chirality driven by a versatile heteroscorpionate ligand: self-assembly of a metal helicate by using CH-pi interactions. PMID- 20583063 TI - Anthraquinone sulfonate modified, layered double hydroxide nanosheets for dye sensitized solar cells. PMID- 20583064 TI - Al3Li4(BH4)13: a complex double-cation borohydride with a new structure. AB - The new double-cation Al-Li-borohydride is an attractive candidate material for hydrogen storage due to a very low hydrogen desorption temperature (approximately 70 degrees C) combined with a high hydrogen density (17.2 wt%). It was synthesised by high-energy ball milling of AlCl(3) and LiBH(4). The structure of the compound was determined from image-plate synchrotron powder diffraction supported by DFT calculations. The material shows a unique 3D framework structure within the borohydrides (space group=P-43n, a=11.3640(3) A). The unexpected composition Al(3)Li(4)(BH(4))(13) can be rationalized on the basis of a complex cation [(BH(4))Li(4)](3+) and a complex anion [Al(BH(4))(4)](-). The refinements from synchrotron powder diffraction of different samples revealed the presence of limited amounts of chloride ions replacing the borohydride on one site. In situ Raman spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TG) and thermal desorption measurements were used to study the decomposition pathway of the compound. Al-Li-borohydride decomposes at approximately 70 degrees C, forming LiBH(4). The high mass loss of about 20 % during the decomposition indicates the release of not only hydrogen but also diborane. PMID- 20583065 TI - Fullerene derivatives that bear aliphatic chains as unusual surfactants: hierarchical self-organization, diverse morphologies, and functions. AB - Conventionally, amphiphiles are composed of hydrophobic and hydrophilic units. They are able to exhibit a wide variety of structures depending on the environment. Such features have been applied in supramolecular chemistry, by which apolar and polar groups are implemented in the molecular design. Here we present an attractive approach to introduce unique amphiphilicity. Relatively simple fullerene (C(60)) derivatives that bear long aliphatic chains behave as uncommon surfactants in organic media. Although two hydrophobic units are used to assemble the derivatives, slight differences in their polarity and chemical nature may make them incompatible and thus arrange them in microphase-separated mesostructures as lamellar ones. These assemblies are maintained by relatively weak forces, pi-pi interactions among C(60) moieties and van der Waals forces between alkyl chains. Therefore, the derivatives can undergo "supramolecular polymorphism" by which different supramolecular assemblies arise by changing the conditions of assembly. A simple modification in their substituent motif of derivatives influences the intermolecular interactions and provides a wide variety of supramolecular materials. PMID- 20583066 TI - Reactions of alkynes with [RuCl(cyclopentadienyl)] complexes: the important first steps. AB - Cyclopentadienyl-ruthenium half-sandwich complexes with eta(2)-bound alkyne ligands have been suggested as catalytic intermediates in the early stages of Ru catalyzed reactions with alkynes. We show that electronically unsaturated complexes of the formula [RuCl(Cp--)(eta(2)-RC[triple bond]CR')] can be stabilized and crystallized by using the sterically demanding cyclopentadienyl ligand Cp-- (Cp--=eta(5)-1-methoxy-2,4-tert-butyl-3-neopentyl-cyclopentadienyl). Furthermore we demonstrate that [RuCl(2)(Cp==)](2) is an active and regioselective catalyst for the [2+2+2] cyclotrimerization of alkynes. The first elementary steps of the reaction of mono(eta(2)-alkyne) complexes containing {RuCl(Cp*)} (Cp*=eta(5)-C(5)Me(5)) and {RuCl(Cp--)} fragments with alkynes were investigated by DFT calculations at the M06/6-31G* level in combination with a continuum solvent model. Theoretical results are able to rationalize and complement the experimental findings. The presence of the sterically demanding Cp - ligand increases the activation energy required for the formation of the corresponding di(eta(2)-alkyne) complexes, enhancing the initial regioselectivity, but avoiding the evolution of the system towards the expected cyclotrimerization product when bulky substituents are present. Theoretical results also show that the electronic structure and stability of a metallacyclic intermediate is strongly dependent on the nature of the substituents present in the alkyne. PMID- 20583067 TI - Hierarchical crystalline superstructures of conducting polymers with homohelicity. PMID- 20583068 TI - On the NH effect in ruthenium-catalysed hydrogenation of ketones: rational design of phosphine-amino-alcohol ligands for asymmetric hydrogenation of ketones. PMID- 20583069 TI - Biaxial nematic mesophases from shape-persistent mesogens with a fluorenone bending unit. PMID- 20583070 TI - Bionanoprobes with excellent two-photon-sensitized Eu3+ luminescence properties for live cell imaging. PMID- 20583071 TI - Coordination chemistry without frontiers: a short analysis and applications of a new method for the description of closed coordination clusters. PMID- 20583072 TI - Nucleophilic silylenoid character of stable phosphonium sila-ylides. PMID- 20583073 TI - Sodium-mediated magnesiation of thiophene and tetrahydrothiophene: structural contrasts with furan and tetrahydrofuran. PMID- 20583074 TI - When emotionality trumps reason: a study of individual processing style and juror bias. AB - "Cognitive Experiential Self Theory" (CEST) postulates that information processing proceeds through two pathways, a rational one and an experiential one. The former is characterized by an emphasis on analysis, fact, and logical argument, whereas the latter is characterized by emotional and personal experience. We examined whether individuals influenced by the experiential system (E-processors) are more susceptible to extralegal biases (e.g. defendant attractiveness) than those influenced by the rational system (R-processors). Participants reviewed a criminal trial transcript and defendant profile and determined verdict, sentencing, and extralegal susceptibility. Although E processors and R-processors convicted attractive defendants at similar rates, E processors were more likely to convict less attractive defendants. Whereas R processors did not sentence attractive and less attractive defendants differently, E-processors gave more lenient sentences to attractive defendants and harsher sentences to less attractive defendants. E-processors were also more likely to report that extralegal factors would change their verdicts. Further, the degree to which emotionality trumped rationality within an individual, as measured by a novel scoring method, linearly correlated with harsher sentences and extralegal influence. In sum, the results support an "unattractive harshness" effect during guilt determination, an attraction leniency effect during sentencing and increased susceptibility to extralegal factors within E processors. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID- 20583075 TI - Safety of small-for-size grafts in adult-to-adult living donor liver transplantation using the right lobe. AB - The problem of graft size is one of the critical factors limiting the expansion of adult-to-adult living donor liver transplantation (LDLT). We compared the outcome of LDLT recipients who received grafts with a graft-to-recipient weight ratio (GRWR) < 0.8% or a GRWR > or = 0.8%, and we analyzed the risk factors affecting graft survival after small-for-size grafts (SFSGs) were used. Between June 1997 and April 2008, 427 patients underwent LDLT with right lobe grafts at the Department of Surgery of Samsung Medical Center. Recipients were divided into 2 groups: group A with a GRWR < 0.8% (n = 35) and group B with a GRWR > or = 0.8% (n = 392). We retrospectively evaluated the recipient factors, donor factors, and operative factors through the medical records. Small-for-size dysfunction (SFSD) occurred in 2 of 35 patients (5.7%) in group A and in 14 of 392 patients (3.6%) in group B (P = 0.368). Graft survival rates at 1, 3, and 5 years were not different between the 2 groups (87.8%, 83.4%, and 74.1% versus 90.7%, 84.5%, and 79.4%, P = 0.852). However, when we analyzed risk factors within group A, donor age and middle hepatic vein tributary drainage were significant risk factors for graft survival according to univariate analysis (P = 0.042 and P = 0.038, respectively). Donor age was the only significant risk factor for poor graft survival according to multivariate analysis. The graft survival rates of recipients without SFSD tended to be higher than those of recipients with SFSD (85.3% versus 50.0%, P = 0.074). The graft survival rates of recipients with grafts from donors < 44 years old were significantly higher than those of recipients with grafts from donors > or = 44 years old (92.2% versus 53.6%, P = 0.005). In conclusion, an SFSG (GRWR < 0.8%) can be used safely in adult-to-adult right lobe LDLT when a recipient is receiving the graft from a donor younger than 44 years. PMID- 20583077 TI - Small-for-size graft: not defined solely by being small for size. PMID- 20583078 TI - Immunosuppression, cancer, and the long-term outcomes after liver transplantation: can we do better? PMID- 20583079 TI - Urgent revascularization for hepatic artery thrombosis: maybe good for the few, definitely good for the many. PMID- 20583080 TI - Improvement in hepatopulmonary syndrome after methadone withdrawal: a case report with implications for disease mechanism. AB - Spontaneous resolution of hepatopulmonary syndrome (HPS) without liver transplantation or improvement in the underlying liver disease has rarely been reported in the literature. Increased endogenous production of nitric oxide has been implicated in the pathogenesis of HPS. We report the case of a 50-year-old man with hepatitis C cirrhosis who demonstrated dramatic improvement in HPS after withdrawal from chronic methadone therapy. We speculate on the potential role of opiate receptors in the pulmonary vasculature and their effect on nitric oxide signaling as a potential mechanism accounting for the patient's clinical improvement. PMID- 20583081 TI - Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation. AB - In contrast to other solid organ transplantations, liver grafts have tolerogenic properties. Animal models indicate that donor leukocytes transferred into the recipient after liver transplantation (LTX) play a relevant role in this tolerogenic phenomenon. However, the specific donor cell types involved in modulation of the recipient alloresponse are not yet defined. We hypothesized that this unique property of liver grafts may be related to their high content of organ-specific natural killer (NK) and CD56(+) T cells. Here, we show that a high proportion of hepatic NK cells that detach from human liver grafts during pretransplant perfusion belong to the CD56bright subset, and are in an activated state (CD69(+)). Liver NK cells contained perforin and granzymes, exerted stronger cytotoxicity against K562 target cells when compared with blood NK cells, and secreted interferon-gamma, but no interleukin-10 or T helper 2 cytokines, upon stimulation with monokines. Interestingly, whereas the CD56bright subset is classically considered as noncytolytic, liver CD56bright NK cells showed a high content of cytolytic molecules and degranulated in response to K562 cells. After LTX, but not after renal transplantation, significant numbers of donor CD56dim NK and CD56(+) T cells were detected in the recipient circulation for approximately 2 weeks. In conclusion, during clinical LTX, activated and highly cytotoxic NK cells of donor origin are transferred into the recipient, and a subset of them mixes with the recirculating recipient NK cell pool. The unique properties of the transferred hepatic NK cells may enable them to play a role in regulating the immunological response of the recipient against the graft and therefore contribute to liver tolerogenicity. PMID- 20583082 TI - Use of model for end-stage liver disease exception points for early liver transplantation and successful reversal of hepatic myelopathy with a review of the literature. AB - Hepatic myelopathy (HM) is a rarely reported disorder characterized by progressive spastic paraparesis due to impaired corticospinal tract function in the setting of cirrhosis or portosystemic shunting. HM has not to date been recognized as a Model for End-Stage Liver Disease (MELD) exception for transplantation. Outcomes for a small number of patients from Europe and Asia who have undergone liver transplantation (LT) for HM suggest a potential neurological benefit, especially with earlier transplantation. We report the first use of MELD exception points for the condition of HM to enable early LT resulting in the reversal of marked spastic paraparesis. Our patient, whose myelopathy had markedly progressed without further hepatic decompensation, underwent LT 14 months after the diagnosis of HM with an adjusted MELD score of 30, which was granted as a United Network for Organ Sharing exception. After LT, there was significant neurological improvement as the patient progressed from wheelchair dependency to full ambulation. We reviewed the literature of other HM patients who had undergone LT. With our patient, there were in all 15 reported cases of LT in individuals with HM. LT can lead to a marked improvement in HM, particularly in the earlier clinical stages of the disorder. Early LT can be accomplished, as in our case, by the submission of an appeal for a MELD upgrade. PMID- 20583083 TI - Reply: Ethical perspectives on living donor organ transplantation in Asia. PMID- 20583084 TI - Prospects for stem cell transplantation in the treatment of hepatic disease. AB - Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated. PMID- 20583085 TI - Escape hepatitis B virus mutations in recipients of antibody to hepatitis B core antigen-positive liver grafts receiving hepatitis B immunoglobulins. AB - A variety of prophylactic strategies are used to prevent the risk of hepatitis B virus (HBV) transmission from antibody to hepatitis B core antigen (anti-HBc) positive donors. The mechanisms underlying the failure of HBV immunoglobulin monoprophylaxis have been poorly evaluated. Seventy-seven anti-HBc-positive grafts were used in 21 hepatitis B surface antigen (HBsAg)-positive recipients and 56 HBsAg-negative recipients. HBsAg-positive recipients received prophylaxis comprising hepatitis B immunoglobulins (HBIG) and antiviral agents, 45 HBsAg negative recipients received a modified HBIG regimen, and 11 HBsAg-negative recipients received no prophylaxis. Both donors and recipients were screened for HBsAg, antibody to HBsAg (anti-HBs) and anti-HBc in their sera and for HBV DNA in both their sera and liver. S gene mutations were investigated after HBV reinfection. HBV infection occurred in 15 HBsAg-negative recipients (19.4%) at a median interval of 16 months (range = 6-67 months) post-transplant and in none of the HBsAg-positive recipients. HBV infections were observed in 31.6% of HBV-naive recipients and 7.7% of HBV-immune recipients receiving HBIG prophylaxis versus 100% of HBV-naive recipients (P = 0.0068) and 33% of HBV-immune recipients (P = 0.08) with no such prophylaxis. S gene mutations were identified in 9 recipients. In conclusion, priority should be given to using anti-HBc positive grafts for HBsAg-positive or HBV-immune recipients. Our study has confirmed the high risk of HBV transmission to naive recipients. HBIG monoprophylaxis was associated with a significant risk of de novo HBV infection and HBV escape mutations. In these patients, we therefore recommend prophylaxis with lamivudine or new nucleos(t)ides analogues. The potential benefits of HBIG prophylaxis combined with antiviral drugs require further evaluations. Long-term prophylaxis is needed because of the long interval of de novo HBV infection post-transplant in some patients. PMID- 20583086 TI - The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. AB - To expand the donor liver pool, ways are sought to better define the limits of marginally transplantable organs. The Donor Risk Index (DRI) lists 7 donor characteristics, together with cold ischemia time and location of the donor, as risk factors for graft failure. We hypothesized that donor hepatic steatosis is an additional independent risk factor. We analyzed the Scientific Registry of Transplant Recipients for all adult liver transplants performed from October 1, 2003, through February 6, 2008, with grafts from deceased donors to identify donor characteristics and procurement logistics parameters predictive of decreased graft survival. A proportional hazard model of donor variables, including percent steatosis from higher-risk donors, was created with graft survival as the primary outcome. Of 21,777 transplants, 5051 donors had percent macrovesicular steatosis recorded on donor liver biopsy. Compared to the 16,726 donors with no recorded liver biopsy, the donors with biopsied livers had a higher DRI, were older and more obese, and a higher percentage died from anoxia or stroke than from head trauma. The donors whose livers were biopsied became our study group. Factors most strongly associated with graft failure at 1 year after transplantation with livers from this high-risk donor group were donor age, donor liver macrovesicular steatosis, cold ischemia time, and donation after cardiac death status. In conclusion, in a high-risk donor group, macrovesicular steatosis is an independent risk factor for graft survival, along with other factors of the DRI including donor age, donor race, donation after cardiac death status, and cold ischemia time. PMID- 20583088 TI - Thrombelastograph platelet mapping in a patient receiving antiplatelet therapy. PMID- 20583090 TI - Reply: Liver grafts from donors with central nervous system tumors: a single center perspective. PMID- 20583089 TI - Management of splenic artery aneurysms in liver transplant recipients. PMID- 20583091 TI - Long-term results of urgent revascularization for hepatic artery thrombosis after pediatric liver transplantation. AB - Hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) is a serious complication resulting in bile duct necrosis and often requiring retransplantation. Immediate surgical thrombectomy/thrombolysis has been reported to be a potentially successful treatment for restoring blood flow and avoiding urgent retransplantation. The long-term results of this strategy remain to be determined. In 232 pediatric liver transplants, we analyzed long term outcomes after urgent revascularization for early HAT. HAT developed in 32 patients (13.7%). In 16 children (50%), immediate surgical thrombectomy was performed in an attempt to salvage the graft. Fourteen patients (44%) underwent urgent retransplantation, and 2 (6%) died before further intervention. Immediate thrombectomy resulted in long-term restoration of the hepatic artery flow in 6 of 16 patients (38%) and in 1- and 5-year graft and patient survival rates of 83% and 67%, respectively. In 10 patients, revascularization was unsuccessful, and retransplantation was inevitable. The 1- and 5-year patient survival rates in this group decreased to 50% and 40%, respectively. After immediate retransplantation, the 5-year patient survival rate was 71%. In conclusion, immediate surgical thrombectomy for HAT after pediatric OLT results in long-term graft salvage in about one-third of patients. However, when thrombectomy is unsuccessful, long-term patient survival is lower than the survival of patients who underwent immediate retransplantation. PMID- 20583092 TI - Increased incidence of early de novo cancer in liver graft recipients treated with cyclosporine: an association with C2 monitoring and recipient age. AB - The goal of this study was to determine the risk factors for de novo cancer after liver transplantation (LTx). Retrospective analyses were performed in 385 LTx patients who underwent transplantation between 1986 and 2007. In total, 50 (13.0%) recipients developed de novo malignancy. The cumulative incidence of de novo cancer at 1, 5, 10, and 15 years after LTx was 2.9% +/- 0.9%, 10.5% +/- 1.8%, 19.4% +/- 3.0%, and 33.6% +/- 6.8%, respectively. The standardized incidence ratio of malignancy in LTx patients compared to the general population was 2.2 (95% confidence interval: 1.6-2.8). After excluding posttransplant lymphoproliferative disorder and skin cancer, patients with de novo cancer had a significantly lower survival rate compared to recipients who remained cancer free. The identified univariate risk factors for de novo cancer were cyclosporine A (CsA) treatment, time period of LTx, and recipient age. In multivariate analysis, only CsA treatment emerged as an independent risk factor for de novo cancer, which was attributed to more aggressive cancer types. A surprising finding was that CsA treatment specifically enhanced cancer risk in patients who underwent transplantation after 2004, when C(2) monitoring (blood concentration at 2 hours postdose) was introduced. In addition, these patients showed a significantly lower acute rejection rate, which might reflect a more robust immunosuppressive status caused by the CsA-C(2) regimen. When age was considered, only patients < or =50 years had a higher cancer rate when treated with CsA compared to treatment with tacrolimus. Our data suggest that, compared to tacrolimus treatment, CsA treatment with C(2) monitoring or in younger patients of < or =50 years is associated with a higher early de novo cancer risk after LTx. PMID- 20583093 TI - All-in-one ex vivo self-reconstruction technique using an autologous inferior vena cava for a right lobe liver graft with multiple and complex venous orifices. PMID- 20583094 TI - Analysis of serine-threonine kinase specificity using arrayed positional scanning peptide libraries. AB - Protein kinases vary substantially in their consensus phosphorylation motifs, the residues that are either preferred or deselected by the kinase at specific positions surrounding the phosphorylation site. The protocol described here is used to rapidly determine phosphorylation motifs for serine-threonine kinases. The procedure involves screening an arrayed combinatorial peptide library consisting of 198 biotinylated substrates. Peptides are phosphorylated by the kinase of interest in the presence of radiolabeled ATP and then captured on streptavidin membrane. The membrane is subsequently washed, dried, and exposed to a phosphor screen to visualize and quantify incorporation of radiolabel into the peptides. The phosphorylation motif is thereby derived from the relative extent of phosphorylation of each peptide in the array. PMID- 20583095 TI - Visualization of kinase activity with FRET-based activity biosensors. AB - Genetically encodable FRET-based kinase activity reporters (KARs) enable real time monitoring of kinase activity dynamics in living cells with high spatiotemporal resolution. This unit describes a general protocol for utilizing KARs to visualize kinase activity in living mammalian cells with fluorescence microscopy. PMID- 20583096 TI - Analysis of protein tyrosine phosphatases and substrates. AB - Protein tyrosine phosphorylation is a reversible post-translational modification that is essential for life in eukaryotic cells. The combinatorial action of both protein tyrosine kinases and protein tyrosine phosphatases (PTPs) determines the net level of cellular tyrosine phosphorylation. This unit discusses methods to determine the level of protein tyrosine phosphatase activity and methods for discovering novel substrates for protein tyrosine phosphatases. PMID- 20583097 TI - Fluorescent peptide assays for protein kinases. AB - Protein kinases are enzymes that regulate many cellular events in eukaryotic cells, such as cell-cycle progression, transcription, metabolism, and apoptosis. Protein kinases each have a conserved ATP-binding site, as well as one or more substrate-binding site(s) that exhibit recognition features for a protein substrate. Thus, by bringing ATP and a substrate into close proximity, each protein kinase can modify its substrate by transferring the gamma phosphate of the ATP molecule to a serine, threonine, or tyrosine residue on the substrate. In such a way, signaling pathways downstream from the substrate can be regulated, dependent on the phosphorylated versus dephosphorylated forms of the substrate. This unit describes an assay employing a fluorescent peptide substrate to measure the incorporation of non-radiolabeled phosphate. The assay is based on the principle that the phosphorylation of the peptide substrate leads to an increase in the fluorescence emission intensity of an appended fluorophore. PMID- 20583098 TI - ChIP-Seq: a method for global identification of regulatory elements in the genome. AB - This unit describes ChIP-Seq methodology, which involves chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (Seq), and enables the genome-wide identification of binding sites of transcription factors (TFs) and other DNA-binding proteins. The process is initiated by cross-linking DNA and DNA-bound proteins. Subsequently, chromatin is isolated from nuclei and subjected to sonication. An antibody against a specific TF or DNA-binding protein is then used to immunoprecipitate specific DNA-TF complexes. ChIP DNA is purified, sequencing adapters are ligated, and 30- to 35-nucleotide (nt) sequence reads are generated. The sequence of the DNA fragments is mapped back to the reference genome for determination of the binding sites. PMID- 20583099 TI - Bisulfite sequencing of DNA. AB - Exact positions of 5-methylcytosine (m(5)C) on a single strand of DNA can be determined by bisulfite genomic sequencing (BGS). Treatment with bisulfite ion preferentially deaminates unmethylated cytosines, which are then converted to uracil upon desulfonation. Amplifying regions of interest from deaminated DNA and sequencing products cloned from amplicons permits determination of methylation at single-nucleotide resolution along single DNA molecules, which is not possible with other methylation analysis techniques. This unit describes a BGS technique suitable for most DNA sources, including formaldehyde-fixed tissue. Considerations for experimental design and common sources of error are discussed. PMID- 20583101 TI - Mortality in a cohort of Danish patients with fibromyalgia: increased frequency of suicide. AB - OBJECTIVE: A previous study demonstrated an association between self-reported widespread body pain and increased mortality. The aim of this study was to analyze whether fibromyalgia (FM) and FM-like symptoms are related to increased mortality. METHODS: From hospital records, we identified 1,361 patients referred during the period 1984-1999 because of the suspicion of FM. The cases were reviewed by reviewers who were blinded to the outcome. The cohort was followed up for a total of 5,295 person-years at risk and was linked to the Danish Mortality Register. Using the number of years at risk and sex-, age-, and calendar-specific mortality rates from the general population, cause-specific standardized mortality ratios [SMRs] were calculated. RESULTS: We observed no overall increased mortality among patients with FM. Among the 1,269 female patients, the SMRs (95% confidence intervals [95% CIs]) for an increased risk of death from suicide, liver cirrhosis/biliary tract disease, and cerebrovascular disease were 10.5 (95% CI 4.5-20.7), 6.4 (95% CI 2.3-13.9), and 3.1 (95% CI 1.1-6.8), respectively. The suicide risk was increased at the time of diagnosis and remained increased after 5 years. Patients meeting the American College of Rheumatology criteria for FM and patients with possible FM had the same cause specific mortality pattern. No increased cause-specific mortality was observed in the 84 male patients. CONCLUSION: The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup. The results also suggest that risk factors for liver disease and cerebrovascular disease should be evaluated in patients with FM. PMID- 20583100 TI - Chondroprotective role of the osmotically sensitive ion channel transient receptor potential vanilloid 4: age- and sex-dependent progression of osteoarthritis in Trpv4-deficient mice. AB - OBJECTIVE: Mechanical loading significantly influences the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. Transient receptor potential vanilloid 4 (TRPV4) is a Ca(++)-permeable ion channel that is highly expressed by articular chondrocytes and can be gated by osmotic and mechanical stimuli. The goal of this study was to determine the role of Trpv4 in the structure of the mouse knee joint and to determine whether Trpv4(-/-) mice exhibit altered Ca(++) signaling in response to osmotic challenge. METHODS: Knee joints of Trpv4(-/-) mice were examined histologically and by microfocal computed tomography for osteoarthritic changes and bone structure at ages 4, 6, 9, and 12 months. Fluorescence imaging was used to quantify chondrocytic Ca(++) signaling within intact femoral cartilage in response to osmotic stimuli. RESULTS: Deletion of Trpv4 resulted in severe osteoarthritic changes, including cartilage fibrillation, eburnation, and loss of proteoglycans, that were dependent on age and male sex. Subchondral bone volume and calcified meniscal volume were greatly increased, again in male mice. Chondrocytes from Trpv4(+/+) mice demonstrated significant Ca(++) responses to hypo-osmotic stress but not to hyperosmotic stress. The response to hypo-osmotic stress or to the TRPV4 agonist 4alpha-phorbol 12,13-didecanoate was eliminated in Trpv4(-/-) mice. CONCLUSION: Deletion of Trpv4 leads to a lack of osmotically induced Ca(++) signaling in articular chondrocytes, accompanied by progressive, sex-dependent increases in bone density and osteoarthritic joint degeneration. These findings suggest a critical role for TRPV4-mediated Ca(++) signaling in the maintenance of joint health and normal skeletal structure. PMID- 20583102 TI - Role of Th17 cells in human autoimmune arthritis. AB - OBJECTIVE: To delineate the role of Th17 cells in the pathogenesis of autoimmune arthritides. METHODS: Th17 cells were analyzed in well-defined homogeneous cohorts of patients with the prototypical autoimmune arthritides rheumatoid arthritis (RA) and psoriatic arthritis (PsA), grouped according to patients who had very early active RA (n = 36; mean disease duration 2.8 months, Disease Activity Score in 28 joints 5.0) and those who had very early active PsA (n = 20; mean disease duration 2.3 months), none of whom had received treatment with glucocorticoids or disease-modifying antirheumatic drugs, as well as patients with established RA (n = 21; mean disease duration 68 months) who were considered either responders or nonresponders to therapy. Groups of healthy individuals and patients with osteoarthritis (a noninflammatory arthritis) were used as control cohorts. Expression of T lineage-specific transcription factors (RORC, T-bet, GATA-3, and FoxP3) and the response of CD4 T cells to Th17 cell-inducing conditions were analyzed in vitro. RESULTS: The frequencies of Th17 cells and levels of interleukin-17 strongly correlated with systemic disease activity at both the onset and the progression of RA or PsA. The values were reduced to control levels in patients with treatment-controlled disease activity. Th17 cells were enriched in the joints, and increased frequencies of synovial Th17 cells expressed CCR4 and CCR6, indicative of selective migration of Th17 cells to the joints. The intrinsically elevated expression of RORC, accompanied by biased Th17 cell development, and the resistance of Th17 cells to a natural cytokine antagonist in patients with RA and patients with PsA were suggestive of the underlying molecular mechanisms of uncontrolled Th17 activity in these patients. CONCLUSION: Th17 cells play an important role in inflammation in human autoimmune arthritides, both at the onset and in established disease. PMID- 20583103 TI - Targeting ADAM-17/notch signaling abrogates the development of systemic sclerosis in a murine model. AB - OBJECTIVE: Systemic sclerosis (SSc) is characterized by the fibrosis of various organs, vascular hyperreactivity, and immunologic dysregulation. Since Notch signaling is known to affect fibroblast homeostasis, angiogenesis, and lymphocyte development, we undertook this study to investigate the role of the Notch pathway in human and murine SSc. METHODS: SSc was induced in BALB/c mice by subcutaneous injections of HOCl every day for 6 weeks. Notch activation was analyzed in tissues from mice with SSc and from patients with scleroderma. Mice with SSc were either treated or not treated with the gamma-secretase inhibitor DAPT, a specific inhibitor of the Notch pathway, and the severity of the disease was evaluated. RESULTS: As previously described, mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase I antibodies. The Notch pathway was hyperactivated in the skin, lung, fibroblasts, and splenocytes of diseased mice and in skin biopsy samples from patients with scleroderma. ADAM-17, a proteinase involved in Notch activation, was overexpressed in the skin of mice and patients in response to the local production of reactive oxygen species. In HOCl-injected mice, DAPT significantly reduced the development of skin and lung fibrosis, decreased skin fibroblast proliferation and ex vivo serum-induced endothelial H(2)O(2) production, and abrogated the production of anti-DNA topoisomerase I antibodies. CONCLUSION: Our results show the pivotal role of the ADAM-17/Notch pathway in SSc following activation by reactive oxygen species. The inhibition of this pathway may represent a new treatment of this life-threatening disease. PMID- 20583104 TI - Observational study to determine predictors of rheumatology clinic visit provider contact time. AB - OBJECTIVE: To address perceived inefficiencies in an academic rheumatology practice, a timing/work-flow evaluation was initiated to determine the factors that predict the provider contact time (PCT), i.e., the amount of time that attending physicians spend with patients during an outpatient encounter. METHODS: This prospective observational study was conducted at the University of Colorado Hospital Rheumatology Clinic for return patient visits in early 2008. Each patient encounter was subdivided into components, and the time for each component was recorded. Up to 20 return-visit encounters per provider were randomly selected for inclusion. Multivariate linear regression was used to predict the time, in minutes, that providers spent with patients, and logistic regression was used to determine the time intervals associated with the patient's perception that the visit ran on time. RESULTS: Variables associated with increased PCT were whether a procedure was performed in the clinic (P = 0.037) and whether the visit occurred in the afternoon (P < 0.025). For every minute a provider was late in beginning to see a patient, the PCT decreased by 0.32 minutes (95% confidence interval [95% CI] 0.15, 0.49). Variables associated with the patient's perception that the visit ran on time included the check-in to vitals delay (odds ratio [OR] 0.95; 95% CI 0.92, 0.99) and the provider delay (OR 0.92; 95% CI 0.86, 0.99). CONCLUSION: The patient's punctuality and the presence of a resident are not significantly associated with the time that a provider spends with a patient. However, the degree to which the provider runs late was associated with decreased PCT and diminishes the patient's perception that the visit is running on time. PMID- 20583106 TI - Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis. AB - OBJECTIVE: To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein-induced myositis (CIM). METHODS: Beta(2)-microglobulin-null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically. RESULTS: The incidence of myositis development was significantly lower in beta2-microglobulin null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell-induced muscle injuries were significantly more severe than the CD4 T cell-induced muscle injuries. CONCLUSION: Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM. PMID- 20583105 TI - The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis. AB - OBJECTIVE: To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. RESULTS: The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. CONCLUSION: We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM. PMID- 20583107 TI - Enhanced NF-kappaB activation with an inflammasome activator correlates with activity of autoinflammatory disease associated with NLRP3 mutations outside of exon 3: comment on the article by Jeru et al. PMID- 20583109 TI - Pneumocystis jiroveci pneumonia following rituximab treatment in Wegener's granulomatosis. AB - OBJECTIVE: Wegener's granulomatosis (WG) is a devastating small-vessel vasculitis in children. Standard treatment consists of immunosuppressive medications with cyclophosphamide potentially associated with significant infectious side effects, including Pneumocystis jiroveci pneumonia (PCP). Recently, rituximab, a monoclonal antibody against B cells, has successfully been used in refractory disease. METHODS: We describe the first pediatric patient with refractory WG with sinus and lung disease who developed PCP 6 months after treatment with rituximab, while being treated with methotrexate and prednisone. This 9-year-old child had no CD20+ B cells at time of infection, with normal lymphocyte and CD4 counts. RESULTS: This study provides a review of the published literature, including current protocols, which suggest chemoprophylaxis only in WG patients receiving T cell-targeted immunosuppression such as cyclophosphamide. However, clinical and laboratory evidence points toward a possible role of B cells in the defense against PCP. CONCLUSION: Routine PCP chemoprophylaxis should be strongly considered in patients with WG treated with rituximab. PMID- 20583111 TI - Transient receptor potential vanilloid 4 channel as an important modulator of chondrocyte mechanotransduction of osmotic loading. PMID- 20583112 TI - Measuring fatigue in rheumatoid arthritis: a cross-sectional study to evaluate the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional questionnaire, visual analog scales, and numerical rating scales. AB - OBJECTIVE: Current patient-reported outcome measures of fatigue in rheumatoid arthritis (RA) have limitations, providing only a global perspective. This study constructed a questionnaire (the Bristol RA Fatigue Multi-Dimensional Questionnaire [BRAF-MDQ]) from 45 preliminary questions derived from analysis of patient interviews and surveys and explored its structure for fatigue dimensions. The BRAF-MDQ and short BRAF numerical rating scales (NRS) and visual analog scales (VAS) for severity, effect, and ability to cope with fatigue were evaluated for validity. METHODS: Two hundred twenty-nine RA patients with fatigue (VAS score >=5 of 10) completed preliminary BRAF and comparator fatigue scales. Iterative analyses informed item removal or retention in the BRAF-MDQ and identification of subscales (using Cronbach's alpha for internal consistency and factor analysis to identify dimensions). The BRAF-MDQ and short scales were tested in relation to potentially associated variables for criterion and construct validity (Spearman's correlation). RESULTS: The 20-item BRAF-MDQ had good internal consistency (Cronbach's alpha = 0.932), criterion validity (correlation with other fatigue scales: r = 0.643-0.813), and construct validity (correlations with disability, mood, helplessness, and pain: r = 0.340-0.627). Factor analysis showed 4 distinct dimensions (physical fatigue, living with fatigue, cognition fatigue, and emotional fatigue), which correlated well with the RA Multidimensional Assessment of Fatigue scale (r = 0.548-0.834). The BRAF VAS and NRS showed similar criterion and construct validity. CONCLUSION: The BRAF instruments include standardized NRS and VAS for fatigue severity, effect, and coping, are RA specific, and have evidence to support validity. The BRAF-MDQ uniquely measures 4 separate dimensions, which may facilitate development of individually-tailored fatigue management programs. PMID- 20583113 TI - Quality of osteoarthritis management and the need for reform in the US. PMID- 20583114 TI - Robotic surgery of the infratemporal fossa utilizing novel suprahyoid port. AB - OBJECTIVES/HYPOTHESIS: To develop a minimally invasive technique for robotic access to the infratemporal fossa and describe use of a novel suprahyoid port placement. STUDY DESIGN: A cadaveric study to assess feasibility of robotic dissection of the infratemporal fossa using a novel, midline suprahyoid port placement. METHODS: Six complete and two partial dissections of the infratemporal fossa were carried out on one fixed and three fresh cadaveric heads using the da Vinci surgical robot (Intuitive Surgical, Inc., Sunnyvale, CA). The suprahyoid port site was utilized to place one robotic arm into the vallecula. The second arm and 30 degrees camera were placed transorally, and dissections were performed through the lateral pharyngeal wall and into the infratemporal fossa with identification and preservation of the lingual nerve, inferior alveolar nerve, internal and external carotid arteries, jugular vein, and cranial nerves IX-XII. Surgical clips were placed at the extent of dissection, and computed tomography (CT) imaging was obtained after dissections. RESULTS: The transoral and midline suprahyoid port sites provide excellent access to the infratemporal fossa. The midline port site has excellent utility for accessing wide areas of the skull base bilaterally. CT imaging shows surgical clips placed successfully at the skull base foramina of major neurovascular structures. CONCLUSIONS: Robotic surgery offers several advantages over traditional endoscopic surgery with the addition of tremor-free, two-handed technique and microscopic three-dimensional visualization. A midline suprahyoid port placement provides minimally invasive access for excellent exposure of the infratemporal fossa bilaterally. PMID- 20583115 TI - Expression of p53, MDM2, p21, heat shock protein 70, and HPV 16/18 E6 proteins in oral verrucous carcinoma and oral verrucous hyperplasia. AB - BACKGROUND: Oral verrucous hyperplasia is a precancerous lesion of oral verrucous carcinoma. METHODS: This study used immunohistochemistry to examine the expression of p53, murine double minute 2 (MDM2), p21, heat shock protein 70 (HSP 70), and human papillomavirus (HPV) 16/18 E6 proteins in 48 oral verrucous carcinoma and 30 oral verrucous hyperplasia samples. RESULTS: The mean labeling indices of p53, MDM2, p21, HSP 70, and HPV 16/18 E6 proteins in oral verrucous carcinoma samples were 21%, 31%, 7%, 17%, and 0.5%, respectively, and those in oral verrucous hyperplasia samples were 19%, 35%, 11%, 14%, and 0.3%, respectively. CONCLUSIONS: Immunohistochemistry with the above-cited 5 biomarkers could not help differentiate oral verrucous hyperplasia from oral verrucous carcinoma. The low expression of p21 may partially explain abnormal epithelial overgrowth in both verrucous lesions. The pathogenesis of both verrucous lesions may be at least partially attributed to the overexpression of MDM2 protein and moderate expression of HSP 70 protein in both lesions. PMID- 20583117 TI - What is the treatment of the lateral neck in clinically localized sporadic medullary thyroid cancer? PMID- 20583118 TI - Retraction. Effects of recombinant type 1 interferon therapy on human muscle diseases. PMID- 20583119 TI - Digital necroses and vascular thrombosis in severe spinal muscular atrophy. AB - Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons. We report two unrelated patients with severe SMA type I who had only one SMN2 copy and developed ulcerations and necroses of the fingers and toes. Sural nerve biopsy was normal in patient 1, whose affected skin displayed necroses and thrombotic occlusions of small vessels. Corresponding to a mouse model and other patients with similar findings, we believe that severe survival motor neuron (SMN) deficiency may present as vasculopathy. PMID- 20583123 TI - Gabapentin-induced exacerbation of myasthenia gravis. PMID- 20583125 TI - History of outcome measures for myasthenia gravis. AB - This review illustrates how measurements of clinical status in patients with myasthenia gravis have evolved from clinical descriptions and estimates of mortality rates to more sophisticated evaluative instruments, including numerical rating scales that measure strength, endurance, quality of life, and activities of daily living. The rationale and use of weighting and the importance of patient reported outcomes are also discussed. The measurement of the steroid-sparing effect of an immunosuppressant is also reviewed. PMID- 20583124 TI - Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics. AB - Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty-one mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C-reactive protein (CRP) were increased. CRP levels were 5.84 +/- 1.01 ng/ml for controls and 11.24 +/- 1.52 ng/ml for ALS subjects, as determined by enzyme-linked immunoassay. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb-onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%. PMID- 20583127 TI - Serum Mac-2BP does not distinguish men with high grade, large volume prostate cancer from men with benign prostatic hyperplasia. AB - BACKGROUND: Mac-2 binding protein (Mac-2BP) is a secreted protein that has been used as a serum prognostic marker for several types of cancers. A previous study showed that serum Mac-2BP was significantly higher (~2-fold) in men with prostate cancer compared to healthy men. We investigated whether serum Mac-2BP could distinguish men with high grade, large volume prostate cancer from men with benign prostatic hyperplasia (BPH). METHODS: A commercially available ELISA kit was used to measure Mac-2BP in paired pre- and post-prostatectomy sera from 10 men with high grade, large volume prostate cancer, in pre-operative sera from 50 untreated men with high grade, large volume prostate cancer, and in sera from 50 men with clinical symptoms of BPH and biopsy-negative for prostate cancer. Results were analyzed by Student's t-test and receiver operating characteristic (ROC) curves. RESULTS: Levels of Mac-2BP did not decrease in post-prostatectomy sera, and Mac-2BP values were not significantly different in the sera of men with prostate cancer versus those with BPH. CONCLUSION: Serum Mac-2BP does not appear to originate in the prostate and it is unlikely that Mac-2BP can be used for the differential diagnosis of prostate cancer versus BPH. PMID- 20583128 TI - Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. AB - We have previously reported evidence that variation at GABA(A) receptor genes is associated with susceptibility to bipolar disorder with schizophrenia-like psychotic features (Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type) with gene-wide significance at GABRB1, GABRA4, GABRB3, GABRA5, and GABRR3. Here we provide suggestive evidence implicating a sixth member of the gene family, GABRR1 (gene-wide P = 0.0058; experiment-wide corrected significance P = 0.052). PMID- 20583129 TI - Maternal smoking during pregnancy is associated with epigenetic modifications of the brain-derived neurotrophic factor-6 exon in adolescent offspring. AB - Prenatal exposure to maternal cigarette smoking (PEMCS) is associated with variations in brain and behavior in adolescence. Epigenetic mechanisms may mediate some of the consequences of PEMCS through methylation of deoxyribonucleic acid (DNA) in genes important for brain development, such as the brain-derived neurotrophic factor (BDNF). In the current study, we used bisulfite sequencing to assess DNA methylation of the BDNF promoter in the blood of adolescents whose mothers smoked during pregnancy. We demonstrate that PEMCS is associated with higher rates of DNA methylation in the BDNF-6 exon. These results suggest that PEMCS may lead to long-term down-regulation of BDNF expression via the increase of DNA methylation in its promoter region. Such mechanisms could, in turn, lead to modifications in both development and plasticity of the brain exposed in utero to maternal cigarette smoking. PMID- 20583130 TI - Reported occupational respiratory diseases in three Spanish regions. AB - BACKGROUND: In 2002, a voluntary registry of occupational respiratory diseases was initiated in the test phase in Asturias, Catalonia, and Navarre (Spain). Based on data from the fully implemented voluntary registry, we assessed the differences in the incidence and characteristics of the diseases reported in the three regions studied and compared them with those notified to the compulsory official system. METHODS: Physicians whose daily practice includes patients with occupational respiratory diseases were invited to participate. Newly diagnosed cases occurring during 2003 in the work force of the three regions studied were reported on a notification form every 2 months. Data from the compulsory official notification system were obtained from statistics on work-related diseases for possible disability benefits. RESULTS: Five hundred thirty-three new cases, representing a cumulative incidence of 183.52 (168.27-199.78) per million workers per year, were reported. The number of cases and the incidence, overall and for each disease, causes of the diseases, and the occupations varied considerably between regions. The number of cases reported to the voluntary system was more than threefold greater than the number reported to the compulsory official system. CONCLUSIONS: The compulsory scheme for reporting occupational respiratory diseases is seriously under-reporting in the three Spanish regions studied. Our voluntary surveillance program, which showed considerable differences in the characteristics and incidence of these diseases among the regions, appears to be more effective. PMID- 20583131 TI - Expression analysis of putative stem cell markers in human benign and malignant prostate. AB - BACKGROUND: Stem cells were suggested to be present in human prostate cancer as a small population of distinct cells, which may contribute to carcinogenesis, tumor recurrence, and chemoresistance. To identify potential prostatic stem cells, we analyzed the expression of several potential stem cell markers in benign prostate and prostatic adenocarcinoma. METHODS: CD44, CD133, Oct4, SOX2, and EZH2 expression was detected by immunohistochemical (IHC) staining using tissue microarray assays (TMA) composed of benign (non-neoplastic) prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and prostatic adenocarcinoma. Positive staining was defined as 1+ (<10%), 2+ (10-50%), or 3+ (>50%). RESULTS: We found CD44 staining in 97% and 72% of benign + HGPIN and malignant lesions, respectively. CD133 staining was detected in a small fraction (4 of 67) of prostate carcinomas. We found that Oct4 nuclear expression was strongly associated with benign lesions and HGPIN but not prostate cancer (P < 0.05). In most cases, nuclear expression of EZH2 and SOX2 was detected in less than 10% of cells in non-neoplastic prostate glands, HGPINs or prostate adenocarcinomas. Moreover, 27 of 33 SOX2 1+ prostate cancers were also EZH2 1+, whereas all 33 of these cases were CD44+. CONCLUSIONS: Expression of CD44 and Oct4 identified large populations of benign and malignant cells in the prostate, which did not fit the definition of stem cells as a small fraction of the total cell population. Our results suggest that combined expression of embryonic stem cell markers EZH2 and SOX2 might identify potential cancer stem cells as a minor (<10%) subgroup in CD44+ prostatic adenocarcinoma. PMID- 20583132 TI - 1,25-dihydroxyvitamin D(3) and PI3K/AKT inhibitors synergistically inhibit growth and induce senescence in prostate cancer cells. AB - BACKGROUND: 1-Alpha, 25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits proliferation of multiple cancer cell types including prostate cells and upregulates p21 and/or p27, while loss of Pten and PI3K/AKT activation stimulates survival and downregulates p21 and p27. We hypothesized that inhibition of the PI3K/AKT pathway synergizes with the antiproliferative signaling of 1,25(OH)(2)D(3). METHODS: Viability, cell cycle and senescence of cells were evaluated upon combinational treatment with 1,25(OH)(2)D(3) and pharmacological PI3K/AKT inhibitors. RESULTS: Pharmacological inhibitors of PI3K or Akt and 1,25(OH)(2)D(3) synergistically inhibited growth of DU145, LNCaP, primary human prostate cancer cell strains and Pten null mouse prostatic epithelial cells (MPEC). The inhibitors used included API-2 (Triciribine) and GSK690693 which are currently in clinical trials for treatment of cancer. A novel mechanism for antiproliferative effects of 1,25(OH)(2)D(3) in prostate cells, induction of senescence, was discovered. Combination of 1,25(OH)(2)D(3) and AKT inhibitor cooperated to induce G(1) arrest, senescence, and p21 levels in prostate cancer cells. As AKT is commonly activated by PTEN loss, we evaluated the role of Pten in responsiveness to 1,25(OH)(2)D(3) using shRNA knockdown and by in vitro knockout of Pten. MPEC that lost Pten expression remained sensitive to the antiproliferative action of 1,25(OH)(2)D(3), and showed higher degree of synergism between AKT inhibitor and 1,25(OH)(2)D(3) compared to Pten-expressing counterparts. CONCLUSIONS: These findings provide the rationale for the development of therapies utilizing 1,25(OH)(2)D(3) or its analogs combined with inhibition of PI3K/AKT for the treatment of prostate cancer. PMID- 20583133 TI - Expression of cancer/testis antigens in prostate cancer is associated with disease progression. AB - BACKGROUND: The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. METHODS: CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. RESULTS: A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. CONCLUSIONS: Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics. PMID- 20583134 TI - Inhibition of angiopoietin-2 in LuCaP 23.1 prostate cancer tumors decreases tumor growth and viability. AB - BACKGROUND: Angiopoietin-2 is expressed in prostate cancer (PCa) bone, liver, and lymph node metastases, whereas, its competitor angiopoietin-1 has limited expression in these tissues. Therefore, we hypothesized that the inhibition of angiopoietin-2 activity in PCa will impede angiogenesis, tumor growth, and alter bone response in vivo. METHODS: To test our hypothesis we used L1-10, a peptide Fc fusion that inhibits interactions between angiopoietin-2 and its receptor tie2. We blocked angiopoietin-2 activity using L1-10 in established subcutaneous and intra-tibial LuCaP 23.1 xenografts. We then determined the effect of L1-10 on survival, tumor growth, serum PSA, proliferation, microvessel density, and angiogenesis-associated gene expression in subcutaneous tumors. We also determined serum PSA, tumor area, and bone response in intra-tibial tumors. RESULTS: The administration of L1-10 decreased tumor volume and serum PSA, and increased survival in SCID mice bearing subcutaneous LuCaP 23.1 tumors. Histomorphometric analysis, showed a further significant decrease in tumor epithelial area within the L1-10 treated LuCaP 23.1 subcutaneous tumors (P=0.0063). There was also a significant decrease in cell proliferation (P=0.012), microvessel density (P=0.012), and a significant increase in ANGPT-2 and HIF-1alpha mRNA expression (P<=0.05) associated with L1-10 treatment. Alternatively, in LuCaP 23.1 intra-tibial tumors L1-10 treatment did not significantly change serum PSA, tumor area or bone response. CONCLUSIONS: Our results demonstrate that inhibiting angiopoietin-2 activity impedes angiogenesis and growth of LuCaP 23.1 PCa xenografts. Based on these data, we hypothesize that angiopoietin-2 inhibition in combination with other therapies may represent a potential therapy for patients with metastatic disease. PMID- 20583135 TI - Decreased expression of insulin-like growth factor binding protein-5 during N-(4 hydroxyphenyl)retinamide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells: regulation by CCAAT/enhancer-binding protein. AB - Insulin-like growth factor (IGF)-binding protein-5 (IGFBP5), an important member of the IGF axis involved in regulating cell growth and differentiation, acts by modulating IGF signaling and also by IGF-independent mechanisms. We identified IGFBP5 by microarray analysis as a gene differentially regulated during N-(4 hydroxyphenyl)retinamide (4HPR)-induced neuronal differentiation of human retinal pigment epithelial (RPE) cells. IGFBP5 is expressed in human RPE cells, and its expression, mRNA as well as protein, is greatly decreased during the 4HPR-induced neuronal differentiation. Exogenous IGFBP5 does not block the neuronal differentiation indicating that IGFBP5 down-regulation may not be a prerequisite for the neuronal differentiation. IGFBP5 down-regulation, similar to neuronal differentiation, is mediated by the MAPK pathway since U0126, an inhibitor of MEK1/2, effectively blocked it. The overexpression of transcription factor CCAAT/enhancer binding protein-beta (C/EBPbeta) inhibited the 4HPR-induced down regulation of IGFBP5 expression and the neuronal differentiation of RPE cells. Interestingly, the binding of C/EBPbeta to the IGFBP5 promoter was decreased by the 4HPR treatment as indicated by gel shift and chromatin immunoprecipitation analyses. Further, the deletion of C/EBP response element from IGFBP5 promoter markedly decreased the basal promoter activity and abolished its responsiveness to 4HPR treatment in reporter assays, suggesting that the expression of IGFBP5 is regulated by C/EBP. Thus, our results clearly demonstrate that the IGFBP5 expression is down-regulated during 4HPR-induced neuronal differentiation of human RPE cells through a MAPK signal transduction pathway involving C/EBPbeta. PMID- 20583137 TI - Serum early prostate cancer antigen (EPCA) as a significant predictor of incidental prostate cancer in patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia. AB - BACKGROUND: Early prostate cancer antigen (EPCA), a nuclear matrix protein, has been recently suggested as a novel biomarker in malignant lesions of the prostate. This study was to determine whether preoperative serum EPCA levels predicted the presence of incidental prostate cancer (IPCa) in patients undergoing TURP for BPH. METHODS: Serum EPCA levels were measured by ELISA in 449 consecutive patients with symptomatic BPH treated with TURP and 112 healthy men. Predictive performance of serum EPCA levels for IPCa were evaluated. RESULTS: With a cutoff of 10ng/ml, serum EPCA protein had a 100% specificity for the healthy men and a 98% specificity and a 100% sensitivity in separating men with IPCa from those without. Serum EPCA levels in patients with IPCa were significantly higher than in those without and in healthy controls (17.63+/ 2.42ng/ml vs. 5.58+/-1.61 ng/ml and 4.95+/-1.43 ng/ml, all P<0.001), whereas an indwelling transurethral catheter presence and 5alpha-reductase inhibitor therapy had no effect on EPCA levels (P=0.144 and P=0.238, respectively). The area under ROC curves (AUC) showed that serum EPCA level had the best predictive accuracy of all IPCa (AUC: 0.952, 95% CI: 0.912-0.981, P<0.001). Univariate and multivariate Cox regression analyses further demonstrated the independently predictive performance by preoperative serum EPCA (Hazards Ratio: 4.23, 95% CI: 3.62-6.46, P<0.001). CONCLUSIONS: This study firstly shows that EPCA might be used as a highly sensitive and specific serum biomarker to predict IPCa presence and to help reduce the unnecessary biopsies taken before TURP in patients with BPH. PMID- 20583136 TI - Mechanisms of adiponectin-mediated COX-2 induction and protection against iron injury in mouse hepatocytes. AB - Adiponectin (APN)-mediated cyclooxygenase (COX)-2 induction is known to have various protective effects on cardiovascular diseases. However, the molecular mechanisms of APN-mediated COX-2 induction and its protection against iron mediated injury in hepatocytes are still unclear. Herein, we show that AMP mediated peroxisome proliferator-activated receptor (PPAR)alpha activation was attributable to COX-2 induction by APN, which was further confirmed by identifying novel functional PPAR responsive elements (PPREs) in the mouse COX-2 promoter region. Prostaglandin (PG)I2 and PGE2, metabolites of COX-2, time dependently increased in hepatocytes treated with APN. Interestingly, beraprost and misoprostol, respective agonists for PGI2 and PGE2, mimicked the protective effects of APN in iron-mediated inflammation in hepatocytes. The iron dextran activated nuclear factor (NF)-kappaB pathway was correlated with the increased production of inflammatory cytokines including tumor necrosis factor-alpha, intercellular adhesion molecule-1, and monocyte chemotactic protein-1. This was eliminated by administration of APN, whereas blockage of PPARalpha activation, an upstream regulator of COX-2 induction by APN, and COX-2 activation reversed the anti-inflammatory effect of APN, suggesting the crucial role of COX-2 in this event. Herein, we demonstrate that APN-mediated COX-2 induction through a PPARalpha-dependent mechanism, and COX-2 exerted an anti-inflammatory effect of APN in hepatocytes subjected to iron challenge. PMID- 20583138 TI - Cancer morbidity among Danish male urban bus drivers: A historical cohort study. AB - OBJECTIVE: To investigate whether urban bus drivers are at increased risk for cancer. METHODS: Urban bus drivers in a cohort established in 1978 in the three largest cities of Denmark were followed-up in the Danish Cancer Registry until the end of 2003, and relative risks for cancers were estimated. RESULTS: Of 2,037 men included 70% reported in 1978 that they smoked. The standardized incidence ratio (SIR) for cancer in comparison with that of other male residents of the three cities was 1.09 [1.0-1.2]. The excess was due mainly to increased risks for cancers of the bladder (SIR, 1.6; 1.2-2.0) and lung (1.2; 1.0-1.4). In an analysis with internal comparisons and adjustment for smoking, we found no significant associations between duration of employment and increased risks for cancers at these two sites. CONCLUSIONS: In this long-term follow-up study we found little evidence of a causal association between employment as an urban bus driver in Denmark and subsequent cancer. PMID- 20583139 TI - Lung cancer in the melt shops of Ontario steelmakers. PMID- 20583140 TI - The mood disorder questionnaire: its impact on the field [corrected]. PMID- 20583141 TI - Attachment, depression, and cortisol: Deviant patterns in insecure-resistant and disorganized infants. AB - Both attachment insecurity and maternal depression are thought to affect infants' emotional and physiological regulation. In the current study, Strange Situation Procedure (SSP) attachment classifications, and cortisol stress reactivity and diurnal rhythm were assessed at 14 months in a prospective cohort study of 369 mother-infant dyads. Maternal lifetime depression was diagnosed prenatally using the Composite International Diagnostic Interview (CIDI). Insecure-resistant infants showed the largest increase in cortisol levels from pre- to post-SSP; the effect was even stronger when they had depressive mothers. Disorganized children showed a more flattened diurnal cortisol pattern compared to nondisorganized children. Findings are discussed from the perspective of a cumulative risk model. PMID- 20583143 TI - Challenges to bonnet monkey (Macaca radiata) social groups: Mother-infant dyad and infant social interactions. AB - The mother-infant dyad is crucial to early development in a variety of species. The complexity of social groupings in nonhuman primates makes this relationship resilient as well as susceptible to early challenges associated with environmental chaos. Quantitative behavior observations of bonnet monkey mother infant interactions were collected from 28 mother-infant dyads between one and twelve months of age. Social groups were subjected to several prenatal and/or postnatal housing relocations within a single year resulting in two study groups. One group experienced relocations (ATYPICAL, n = 14) and the second group (TYPICAL, n = 14) was conceived and reared in the same location. Behaviors in the ethogram included mother-infant interactions and infant social interactions with other members of the group. Observations between ages of two to four months were analyzed by a mixed model analysis of variance including fixed effects of per and postnatal history (TYPICAL, ATYPICAL), age, and history by age interaction and random effects of mother and infant nested within mother. A significant effect of relocation history was noted on a number of infant behaviors. ATYPICAL infants were out of direct contact with their mother at an earlier age but remained in her proximity. Control of proximity shifted to offsrping in the ATYPICAL group compared to the TYPICAL group. Furthermore, greater social interactions between two and four months of age with other members of the social group as well as the ir mother were observed in the ATYPICAL group. It is suggested that continuous challenge associated with relocation may affect the infant at later developmental ages due to these early differences in ways that are yet unclear. PMID- 20583144 TI - Is infant holding-side bias related to motor asymmetries in mother and child? AB - Studies have revealed a preference for the left hemibody in infant holding in 65 85% of cases. Several investigations have linked this preference to maternal asymmetries. The main goal of the present study was to assess manual and hemispheric asymmetries in both mother and child and delineate their respective influence on holding-side biases. Holding side was assessed by direct observation, and by use of a questionnaire within populations of mother-child dyads. Maternal asymmetries were handedness and hemispheric specialization for perceiving emotions. Infant asymmetries were fetal position, asymmetric tonic neck reflex (ATNR) at birth and handedness at 19 months of age. To that purpose a longitudinal study has been made with infants observed at 2 and 19 months of age. A significant relationship was found between maternal handedness and holding preferences, but no significant relation was obtained between hemispheric specialization and holding preferences. Fetal position in utero but not ATNR, was significantly related to holding-side preferences. Finally, holding side at 2 months was significantly associated with infants' unimanual preferences. PMID- 20583142 TI - Defining age limits of the sensitive period for attachment learning in rat pups. AB - Enhanced odor preference learning and attenuated fear learning characterizes rat pups' attachment learning Sensitive Period for learning the maternal odor. This period terminates at 10 days old (PN10) with increasing endogenous levels of the stress hormone, corticosterone. Increasing Sensitive Period pups' corticosterone prematurely terminates the Sensitive Period, while decreasing corticosterone in older pups delays Sensitive Period termination. Here we extend these findings and define the age range corticosterone alters learning and question whether corticosterone permanently terminates the Sensitive Period. Pups were odor-0.5 mA shock conditioned with either corticosterone increased (PN5-6; 4 mg/kg vs. saline) or decreased (PN15-16; naturally by maternal presence or corticosterone synthesis blocker, Metyrapone). Finally, PN7-8 pups were conditioned with corticosterone and reconditioned without corticosterone to assess whether the Sensitive Period was permanently terminated. Results indicate developmental limits for corticosterone regulation of pup learning are PN6 through PN15. Furthermore, inducing precocious corticosterone induced fear learning was not permanent, since reconditioning without corticosterone enabled odor preference learning. Results suggest pups are protected from learning aversions to maternal odor until approaching weaning. PMID- 20583145 TI - Neonatal amygdala or hippocampus lesions influence responsiveness to objects. AB - Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age and sham-operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala-lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus-lesioned animals' propensity for exploration mirrored that of control animals in some contexts but that of amygdala-lesioned animals in other contexts. At 18 months of age, both amygdala-lesioned and hippocampus-lesioned animals were judged to be less fearful than controls during the testing procedure. Implications for understanding the neurobiology of emotional behavior are discussed. PMID- 20583147 TI - Agenesis of the corpus callosum and congenital lymphedema: A novel recognizable syndrome? AB - We present double first cousins, a girl and a boy, with the uncommon association of agenesis of the corpus callosum and congenital lymphedema. Other features shared by both include oligohydramnios, similar facial dysmorphism, sacral dimple, developmental delay, and sociable personality. While some of these findings overlap with FG syndrome and Hennekam syndrome, the findings in our patients are sufficiently different to exclude these diagnoses. We propose that this is a new syndrome with presumed autosomal recessive inheritance. PMID- 20583146 TI - Anti-histone H1 IgGs from blood serum of systemic lupus erythematosus patients are capable of hydrolyzing histone H1 and myelin basic protein. AB - Novel hydrolytic activity of the anti-histone H1 antibodies (Ab) toward histone H1 and myelin basic protein (MBP) was shown. Blood serum of ten patients with clinically diagnosed systemic lupus erythematosus (SLE), and nine healthy donors (control) were screened for the anti-histone H1 antibody- and anti-MBP antibody mediated specific proteolytic activity. IgGs were isolated by chromatography on Protein G-Sepharose, and four of ten SLE patients appeared to possess IgGs that were capable of cleaving both histone H1 and MBP. Such activity was confirmed to be an intrinsic property of the IgG molecule, since it was preserved at gel filtration at alkaline and acidic pH. At the same time, proteolytic activity was absent in the sera-derived Ab of all healthy donors under control. Anti-histone IgGs were purified by the affinity chromatography on histone H1-Sepharose. Their cross-reactivity toward cationic proteins (histones, lysozyme, and MBP) and their capability of hydrolyzing histone H1 and MBP were detected. However, these IgGs were not cleaving core histones, lysozyme, or albumin. Capability of cleaving histone H1 and MBP was preserved after additional purification of anti-histone H1 IgGs by the HPLC gel filtration. The protease activity of anti-histone H1 IgG Ab was inhibited by serine protease inhibitors. PMID- 20583149 TI - Amish microcephaly: Long-term survival and biochemical characterization. AB - Amish microcephaly (MCPHA, OMIM #607196) is a metabolic disorder that has been previously characterized by severe infantile lethal congenital microcephaly and alpha-ketoglutaric aciduria. All reported patients have been from the Pennsylvania Amish community and homozygous for a p.Gly177Ala mutation in SLC25A19. We present a further male patient with MCPHA born to distantly consanguineous parents in Ontario, Canada with Amish ancestors. Microcephaly was evident at 21 weeks gestation on ultrasound. At birth, the facial appearance and brain MRI scan were characteristic of MCPHA, with the additional features of partial agenesis of the corpus callosum and a closed spinal dysraphic state. Urine levels of alpha-ketoglutaric acid were normal at birth and during metabolic crisis, but were markedly elevated during a time of metabolic stability. A severe lactic acidosis was present during metabolic crises and responded to treatment with a high fat diet. At age 7 years, the child is healthy but has severe microcephaly and profound developmental delay. SLC25A19 has been described as a mitochondria inner membrane transporter for both deoxynucleotides and thiamine pyrophosphate (TPP). The biochemical phenotype of MCPHA may be attributable to decreased activity of the three mitochondrial enzymes that require TPP as a cofactor: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched chain amino acid dehydrogenase. We confirm that alpha-ketoglutaric aciduria is not a constant finding in MCPHA and suggest that a persistent lactic acidemia may be more common. The diagnosis should be considered in patients with severe congenital microcephaly, especially in association with lissencephaly, dysgenesis of the corpus callosum, or a spinal dysraphic state. PMID- 20583150 TI - Pheochromocytoma in a 2.75-year-old-girl with a germline von Hippel-Lindau mutation Q164R. AB - Pheochromocytomas are rare tumors of the adrenal gland occurring sporadically or as part of familial cancer syndromes. Here we report on the case of a pheochromocytoma due to the germline missense mutation c.491A>G (Q164R) in exon 3 of the von Hippel-Lindau gene in a girl as young as 2.75 years. Extended analyses of her relatives showed that the mutation occurred de novo in the patient's father who was subsequently diagnosed with bilateral pheochromocytomas and a retinal angioma. To the best of our knowledge, this is the youngest patient presenting with pheochromocytoma so far described in the literature. The same VHL mutation has been reported in a patient who developed a pheochromocytoma at the age of 10 years; therefore, for known VHL Q164R mutation carriers, we suggest screening for pheochromocytoma beginning at 2 years of age. PMID- 20583151 TI - Vici syndrome associated with unilateral lung hypoplasia and myopathy. PMID- 20583152 TI - Perturbation of the consensus activation site of endothelin-3 leads to Waardenburg syndrome type IV. PMID- 20583153 TI - Constitutional ring chromosome 11 mosaicism in a Wilms tumor patient: Cytogenetic, molecular and clinico-pathological studies. AB - We report on a boy with three cell lines: 46,XY, r(11)(p15.5,q25)[90]/45,XY,-11 [8]/47,XY, r(11)(p15.5,q25)x2[2], with minor anomalies and mental retardation who developed asynchronous bilateral Wilms tumors (WTs). Array comparative genomic hybridization (CGH) performed on peripheral blood leukocytes of the patient led to the identification of a constitutional duplication of 4.8 Mb at 11p15.5 11p15.4. This duplication was found to involve the chromosome of paternal origin, and occurred in tandem on the ring chromosome 11. Despite the constitutive duplication of the paternal 11p15 chromosome region, the patient showed no sign of Beckwith-Wiedemann syndrome. However, the molecular characterization of the two neoplasias was consistent with their independent origin and showed that they arose from the two distinct cellular clones with the ring chromosome, indicating that this anomaly is likely to have caused the patient's susceptibility to WT development. PMID- 20583154 TI - Two patients with Rubinstein-Taybi syndrome and severe pulmonary interstitial involvement. PMID- 20583155 TI - Steinfeld syndrome: Further delineation. AB - Steinfeld syndrome, which was first reported in 1982, is characterized by holoprosencephaly, phocomelia, clefting, congenital heart defects, and other anomalies. There have been two additional reports since then. This report describes a fetus with clinical features consistent with Steinfeld syndrome and it is the first patient with this condition to have extensive genetic evaluation. This appears to be an autosomal dominant syndrome with widely variable expression. The clinical features of this syndrome are reviewed. PMID- 20583156 TI - Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey. AB - Cornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non-CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS. PMID- 20583157 TI - Wormian bones in osteogenesis imperfecta: Correlation to clinical findings and genotype. AB - The presence of a larger than usual number of Wormian bones (accessory skull bones completely surrounded by a suture line) is a well-known radiographic sign of osteogenesis imperfecta (OI), but the phenotypic and genotypic correlates are not well characterized. In the present study we retrospectively analyzed skull radiographs of 195 OI patients (median age 11.8 years, range 0.4-48 years; 100 female). A significant number of Wormian bones (SNWB, defined as the presence of 10 or more Wormian bones) were found in at least one patient in all of the OI types studied (I, III to VII). SNWB were observed in 35% of patients with OI type I, in 96% of patients with OI type III and 78% of patients with OI type IV. SNWB were present in 28% of patients with haploinsufficiency (nonsense and frameshift) mutations in COL1A1, in 96% of patients with helical glycine substitutions in the alpha 1 chain of collagen type I and in 72% of patients with helical glycine substitutions in the alpha 2 chain of collagen type I. Stepwise multivariate logistic regression analysis showed that height z-score, an indicator of disease severity, was inversely related with the prevalence of SNWB. SNWB were visible in 19 of the 26 patients who had skull radiographs in the first year of life, including a 2-week-old newborn. Thus, it appears that SNWB occur more frequently in more severely affected OI patients and seem to develop mostly in utero. PMID- 20583158 TI - Fragile X leads to X chromosome loss: Comments from a cytogeneticist. PMID- 20583159 TI - Sirenomelia and VACTERL association in the offspring of a woman with diabetes. AB - Sirenomelia and VACTERL association are defects of blastogenesis of unknown cause. Although they appear clinically distinct, some epidemiological and experimental studies suggest a common pathogenetic mechanism. We report on the reproductive history of a 28-year-old obese, diabetic mother who had three pregnancies. The first resulted in the birth of a sirenomelic child, the second in a miscarriage, while the third was terminated for fetal malformations, diagnosed post-mortem as VACTERL association. This observation supports the relationship between sirenomelia and VACTERL, which probably represent the two ends of the same phenotypic spectrum. Their occurrence in the same sibship also indicates a possible common cause. The coexistence with maternal diabetes seems more than a chance occurrence and the constellation of malformations observed in the present family may be explained as the pleiotropic effect of the same teratogenic agent interacting with genetic predisposition to diabetes and/or obesity. PMID- 20583161 TI - A new familial insertion, ins(18;9)(q12.2;q33.1q31.1) with a 9q31.1-9q33.1 deletion in a girl with a cleft lip and palate. PMID- 20583162 TI - A patient with Pendred syndrome whose goiter progressed with normal serum thyrotropin and iodine organification. AB - Biallelic mutations of SLC26A4 (encoding pendrin) cause Pendred syndrome (PS), an autosomal recessive genetic disorder with deafness and goiter. The mechanism underlying the development of the goiter is unknown. Here, we report clinical and molecular findings of a patient with PS. This 27-year-old woman was born to nonconsanguineous healthy parents. She was seen at our hospital due to hearing loss at age 3 years, and subsequently developed goiter at age 10 years. From age 15 years, her thyroid gland showed progressive enlargement accompanied by elevation of serum thyroglobulin reaching 10-fold the normal amount. Thyroidal iodine uptake was also increased during goiter progression ((123)I uptake at 24 hr: 20.2% at age 17 years; 69.4% at age 24 years; reference, 8-40), while serum thyrotropin (TSH) levels and iodine organification (examined by the perchrolate or thiocyanate discharge test) remained normal. We sequenced SLC26A4 using standard PCR-based technique, and found one novel (p.T537P) and one recurrent (p.H723R) mutations in a compound heterozygous state. Expression experiments using COS-7 cells showed that the two mutants were entrapped in the endoplasmic reticulum and were poorly localized at the plasma membrane. In summary, a molecularly confirmed PS patient showed goiter progression accompanied by elevated serum thyroglobulin and increased thyroidal iodine uptake, but normal serum TSH levels and normal iodine organification. This implies that some pendrin mutations may involve direct stimulation of thyroid cell proliferation with no TSH hyperstimulation and no iodine organification defect. PMID- 20583164 TI - Maternal uniparental heterodisomy of chromosome 6 in a boy with an isolated cleft lip and palate. AB - We describe a chromosome 6 uniparental disomy (UPD6) in a boy, discovered during a screening for the genetic cause of cleft lip and palate. In the medical literature, almost all documented cases of UPD6 are paternal in origin, and only four were maternal. We present here a report of complete maternal chromosome 6 uniparental heterodisomy. Haplotype analysis was performed using highly polymorphic short tandem repeat (STR) markers that span both arms of chromosome 6. Analysis of these markers revealed the presence of two maternal alleles but no paternal allele, indicating an instance of maternal uniparental heterodisomy. Chromosome analysis of peripheral blood lymphocytes confirmed a normal male karyotype. Advanced maternal age at the time of the infant's birth and heterodisomy of markers around the centromere favors a meiosis-I error. No specific phenotype has been reported for maternal UPD6. Therefore, the cleft lip and palate in the present case probably occurred due to other risk factors. This report provides further evidence that maternal UPD6 has no specific clinical consequences and adds to the collective knowledge of this rare chromosomal finding. PMID- 20583165 TI - The AJMG SEQUENCE: Decoding news and trends for the medical genetics community. Too much? Not enough? PMID- 20583166 TI - After Havasupai litigation, Native Americans wary of genetic research. PMID- 20583168 TI - Rubinstein-Taybi syndrome and Hirschsprung disease in a patient harboring an intragenic deletion of the CREBBP gene. PMID- 20583169 TI - Epidemiology of congenital idiopathic talipes equinovarus in Iowa, 1997-2005. AB - Congenital idiopathic talipes equinovarus (ITEV), also known as clubfoot, is a well-recognized foot deformity. To date, prevalence estimates and descriptive data reported for ITEV have varied due to differences in study methodology. Using population-based surveillance data collected by the Iowa Registry for Congenital and Inherited Disorders, we examined isolated ITEV births delivered from 1997 through 2005 and compared to live births in Iowa during the same time period. An overall prevalence was calculated for live, singleton full-term births only. Prevalence odds ratios (POR)s and 95% confidence intervals (CI)s were examined for selected infant and parental characteristics. The prevalence of isolated ITEV was 11.4 per 10,000 live, singleton full-term births (95% CI = 10.3, 12.6), with no significant variation in prevalence during the study period. Increased PORs were found for males (POR 1.8; 95% CI = 1.5, 2.3) and maternal smoking during pregnancy (POR = 1.5, 95% CI = 1.2, 1.9); low birth weight (<2,500 g) showed an increase among females (POR = 3.2, 95% CI = 1.5, 6.9) but not males (POR = 0.9, 95% CI = 0.3, 2.8). Elevated, but non-significant, PORs were found for season of birth, maternal education, and trimester prenatal care was initiated; decreased PORs were found for fetal presentation, maternal race/ethnicity, parity, area of residence, and parental age at delivery. Our study of a well-defined, homogenous sample suggested that prevalence of isolated ITEV in Iowa was similar to that reported in other population-based studies and provided support for some, but not all, previously reported associations with infant and parental characteristics. More detailed, longitudinal studies of isolated ITEV are recommended. PMID- 20583171 TI - Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1. AB - Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal-recessive disorder resulting from mutations in one of three peroxisomal genes essential for ether lipid biosynthesis, PEX7 (RCDP1), GNPAT (RCDP2), and AGPS (RCDP3). Affected patients have characteristic features including shortening of the proximal long bones, epiphyseal stippling, bilateral cataracts, growth and developmental delays. Whereas the majority of patients have RCDP type 1, around 5% have RCDP type 2 or 3. We identified a patient with RCDP type 2 and an apparent homozygous deletion, c.1428delC, after full sequencing of his GNPAT genes. The father was heterozygous for this mutation, while sequencing of the maternal GNPAT genes revealed only wild-type sequence. Southern analyses performed on parental gDNA did not show evidence of a maternal gene deletion. Amplification and fragment analysis of dinucleotide repeat markers spanning chromosome 1 in the patient and both parents revealed paternal uniparental inheritance. We discuss the potential mechanisms causing uniparental disomy (UPD) in this patient and review the literature on chromosome 1 UPD. The absence of non-RCDP clinical features in this patient was consistent with previous literature supporting the absence of imprinted genes on chromosome 1. This first description of RCDP caused by UPD dramatically changes the parental recurrence risk, highlighting the value of obtaining parental genotypes when the proband has a putative homozygous mutation by sequence analysis. PMID- 20583170 TI - Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate. AB - Cleft lip/palate comprises a large fraction of all human birth defects, and is notable for its significant lifelong morbidity and complex etiology. Several studies have shown that genetic factors appear to play a significant role in the etiology of cleft lip/palate. Human chromosomal region 9q21 has been suggested in previous reports to contain putative cleft loci. Moreover, a specific region (9q22.3-34.1) was suggested to present a approximately 45% probability of harboring a cleft susceptibility gene. Fine mapping of 50 SNPs across the 9q22.3 34.11 region was performed to test for association with cleft lip/palate in families from United States, Spain, Turkey, Guatemala, and China. We performed family-based analyses and found evidence of association of cleft lip/palate with STOM (rs306796) in Guatemalan families (P = 0.004) and in all multiplex families pooled together (P = 0.002). This same SNP also showed borderline association in the US families (P = 0.04). Under a nominal value of 0.05, other SNPs also showed association with cleft lip/palate and cleft subgroups. SNPs in STOM and PTCH genes and nearby FOXE1 were further associated with cleft phenotypes in Guatemalan and Chinese families. Gene prioritization analysis revealed PTCH and STOM ranking among the top fourteen candidates for cleft lip/palate among 339 genes present in the region. Our results support the hypothesis that the 9q22.32 34.1 region harbors cleft susceptibility genes. Additional studies with other populations should focus on these loci to further investigate the participation of these genes in human clefting. PMID- 20583172 TI - Metopic craniosynostosis due to mutations in GLI3: A novel association. AB - We report on the novel association of trigonocephaly and polysyndactyly in two unrelated patients due to mutations within the last third (exon 14) and first third (exon 6) of the GLI3 gene, respectively. GLI3 acts as a downstream mediator of the Sonic hedgehog signal-transduction pathway which is essential for early development; and plays a role in cell growth, specialization, and patterning of structures such as the brain and limbs. GLI3 mutations have been identified in patients with Pallister-Hall, Grieg cephalopolysyndactyly syndrome (GCPS), postaxial polydactyly type A1, preaxial polydactyly type IV, and in one patient with acrocallosal syndrome (ACLS). Furthermore, deletions including the GLI3 gene have been reported in patients with features of GCPS and ACLS. To date, trigonocephaly has not been associated with abnormalities of GLI3 and craniosynostosis is not a feature of GCPS. However, Hootnick and Holmes reported on a father with polysyndactyly and son with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum, considered GCPS thereafter. Guzzetta et al. subsequently described a patient with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum postulating a diagnosis of GCPS, later considered ACLS. In retrospect, these two patients, evaluated prior to mutational analysis, and our patients, with confirmed mutations, likely fall within the GLI3 morphopathy spectrum and may provide a bridge to better understanding those patients with overlapping features of GCPS and ACLS. Based on this observation, we suggest GLI3 studies in patients presenting with this constellation of findings, specifically metopic craniosynostosis with polysyndactyly, in order to provide appropriate medical management and genetic counseling. PMID- 20583173 TI - Seize the day: Newborn screening for SMA. PMID- 20583174 TI - Paternal isodisomy of chromosome 2 as a cause of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. AB - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is an autosomal recessive disorder affecting mitochondrial fatty acid oxidation due to mutations in the HADHA gene. We report on a 22-month-old child who was identified on expanded newborn screening with an abnormal acylcarnitine pattern and increased C14OH. Molecular analysis showed that the child was homozygous for the common mutation, c.1526G > C (p.Glu510Gln) in the HADHA gene. Carrier testing on the parental samples revealed that the father was heterozygous for the mutation whereas the mother did not carry the mutation. Short tandem repeat testing with markers covering both short and long arms of chromosome 2 showed that the child has paternal uniparental isodisomy. We highlight the importance of parental testing in cases of homozygosity in autosomal recessive disorders and its impact on genetic counseling of the family. PMID- 20583175 TI - Recurrence of achondrogenesis type 2 in sibs: Additional evidence for germline mosaicism. AB - Achondrogenesis Type II (ACG2) is a lethal skeletal disorder caused by a dominant mutation in the type II collagen gene (COL2A1). Familial cases have been reported, suggesting both germline and somatic mosaicism. We report on two pregnancies from the same couple with gross, radiologic, and microscopic findings of ACG2. Molecular analysis of the second infant demonstrated heterozygosity for a c.2303G > A transition (p.Gly768Asp) in exon 33 of the COL2A1 gene. Although this mutation could not be proven by molecular studies in the first infant, identical findings in two affected pregnancies support germline mosaicism as the cause of ACG2 in this family. PMID- 20583176 TI - Autosomal dominant prelingual hearing loss with palmoplantar keratoderma syndrome: Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene. AB - About one to three of a 1,000 neonates are afflicted at birth with a serious hearing impairment, with about half of the cases due to genetic causes. Genetic causes of hearing impairment are very heterogeneous. About half of all cases of genetically caused nonsyndromic hearing loss can be ascribed to mutations in the GJB2 gene (connexin 26) and to deletions in the GJB6 gene(connexin 30). Thus far, about 90 different mutations have been identified in the GJB2 gene, of which the majority are autosomal recessive. Ten mutations are autosomal dominant and are in most cases associated with various skin diseases: the keratitis-ichthyosis deafness (KID) syndrome, Vohwinkel syndrome and palmoplantar keratoderma with deafness. To date, the following mutations have been identified which lead to the Palmoplantar Keratoderma syndrome with deafness; Gly59Ala, Gly59Arg, His73Arg, Arg75Trp, and Arg75Gln. We are reporting on four patients with severe hearing impairment. They are members of three unrelated families, who are carriers of mutations Arg75Trp or Arg75Gln, but unlike patients of other publications, do not all present with Palmoplantar Keratoderma syndrome. Our investigations document additional evidence for the correlation between the cited mutations in the GJB2 gene and a syndromic hearing impairment with palmoplantar keratoderma. PMID- 20583177 TI - Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients. AB - Holoprosencephaly (HPE) is genetically heterogeneous. Variable phenotypic manifestations within families with normal and affected patients have been attributed to the number and type of HPE gene mutations. Environmental agents may also contribute to the severity as well as the requirement of multiple hits. Clinical expression is extremely variable ranging from minor facial signs to complex craniofacial anomalies such as cyclopia. Main genes involved include SHH, GLI2, PTCH1, TGIF, ZIC2, TDGF1, SIX3; however, several other candidates have been proposed. Recently it was established that the human growth arrest specific gene 1 (GAS1) is a potential locus for several human craniofacial malformations. Here, we report on four Brazilian patients with GAS1 DNA sequence change who presented variable phenotypical manifestations ranging from classic HPE to HPE-like signs. Two patients had single DNA sequence change in the GAS1 gene, while in other two, an additional mutation in the SHH gene was observed. Clinical manifestations presented by these patients suggest that GAS1 could be considered a candidate locus for one of the types of human HPE. PMID- 20583178 TI - Mandibulofacial dysostosis, severe lower eyelid coloboma, cleft palate, and alopecia: A new distinct form of mandibulofacial dysostosis or a severe form of Johnson-McMillin syndrome? AB - We describe a patient with a phenotype characterized by mandibulofacial dysostosis with severe lower eyelid coloboma, cleft palate, abnormal ears, alopecia, delayed eruption and crowded teeth, and sensorioneural hearing loss. The karyotype and the screening for mutations in the coding region of TCOF1 gene were normal. The clinical signs of our case overlap the new mandibulofacial dysostosis described by Stevenson et al. [2007] and the case with Johnson McMillin syndrome described by Cushman et al. [2005]. The similar clinical signs, mainly, the severe facial involvement observed in these cases suggest that they can represent a new distinct form of mandibulofacial dysostosis or the end of the spectrum of Johnson-McMillin syndrome. PMID- 20583179 TI - A de novo 4q34 interstitial deletion of at least 9.3 Mb with no discernible phenotypic effect. AB - Cytogenetically visible imbalances without phenotypic effect are still rare despite the extent of large-scale copy number variation in the normal population revealed by array CGH. Here we report on a phenotypically normal 30-year-old female with a de novo, cytogenetically visible, interstitial deletion of band 4q34. She was referred following three successive miscarriages, one of which was an intra-uterine death with subendocardial fibroelastosis and dilated cardiomyopathy. There was no other notable medical or family history, she was of normal intelligence and had no dysmorphic features. FISH and Array CGH with a customized 1 Mb BAC array showed that the deletion is a minimum of 9.3 and a maximum of 10.7 Mb in size, between approximately 173 Mb in 4q34.1 and approximately 182 Mb in 4q34.3. The deletion contains only 23 known coding genes giving a low average gene density of approximately 2 genes/Mb. This case further illustrates that (1) sizeable imbalances can be associated with apparent phenotypic normality, (2) gene density is a better guide to possible phenotypic consequences than aberration size, and (3) it is not always safe to assume that de novo imbalances will be causal. PMID- 20583180 TI - Petty syndrome and Fontaine-Farriaux syndrome: Delineation of a single syndrome. AB - In 1990, Petty et al. described two patients representing a novel syndrome with "congenital progeriod" features and neither had classical progeria nor Wiedemann Rautenstrauch syndrome, though many findings were overlapping. One of the cases had previously been described by Dr. Wiedemann in 1948. The key features of Petty syndrome include pre and postnatal growth restriction, decreased subcutaneous fat with loose skin, enlarged fontanelle with underdeveloped calvarium, coronal synostosis, unruly hair pattern with non-uniform distribution, prominent eyebrows, umbilical hernia, distal digital hypoplasia, and normal or near normal development. Significant overlap to other syndromes, particularly the Fontaine Farriaux syndrome, is apparent. In 2004, Ardinger postulated that Petty syndrome, like classical progeria, might be secondary to a defect in the lamin A/C (LMNA) gene. The purpose of this paper is to describe two new unrelated cases of this unique syndrome that further delineate the phenotype, compare to phenotypically similar syndromes, and postulate that Petty syndrome could represent a new laminopathy. In addition, evidence suggesting that the Petty syndrome and Fontaine-Farriaux syndromes are variable expressions of the same condition is discussed. PMID- 20583181 TI - Terminal osseous dysplasia with pigmentary defects (TODPD): Follow-up of the first reported family, characterization of the radiological phenotype, and refinement of the linkage region. AB - Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies and pigmentary skin defects. We have previously described this syndrome in several females from a large, four generation pedigree. The presentation in the affected patients included multiple anomalies, hypertelorism, iris colobomas, punched-out pigmentary abnormalities over the face and scalp, brachydactyly, and digital fibromatosis. The phenotype was highly variable thus suggesting that X-inactivation plays an important role in the expression of the disease. Following our initial description of this condition there have been reports of more cases supporting the initial phenotypic description of this disease. We report on the follow-up of this family at about 10 years from the first evaluation. A detailed clinical follow-up and a review of the skeletal surveys suggests that although the most striking features involves the hands and feet, the skeletal involvement is more generalized and affects many other areas. Our previous linkage analysis has demonstrated mapping to Xq27.3 Xq28. Using a 6,056 SNP array, we have further refined the critical region within the Xq28 region. We have also excluded two candidate genes (FLNA and FAM58A) mapping in the critical region. The identification of the gene responsible for this rare condition will shed light on the molecular pathways leading to the various congenital anomalies of TODPD and will allow a more accurate genetic counseling to the affected individuals. PMID- 20583182 TI - Mixed gonadal dysgenesis in a child with isodicentric Y chromosome: Does the relative proportion of the 45,X line really matter? AB - Isodicentric Y chromosomes [idic(Y)] cause several sex-linked phenotypes ranging from typical Turner syndrome, to phenotypic males, and to those with ambiguous genitalia. The idic(Y) are unstable during mitosis and therefore result in mosaicism with an additional cell line. The associated phenotypic heterogeneity was attributed to variable location of the breakpoints and to the proportion of idic(Y)-containing cells in gonads and other tissues. We report on a phenotypic and cytogenetic characterization of an apparently male patient with ambiguous genitalia and mixed gonadal dysgenesis who was found to be mosaic 45,X/46,X,idic(Y). Unexpectedly, the histologically male gonad showed a predominant proportion of 45,X cells suggesting that additional factors, other than the proportion of the 45,X cell line and the location of the breakpoint, may play a role in gonadal determination and differentiation. Our observation suggests that the timing of the mitotic loss of idic(Y) during gonadal ontogenesis and the proportion of SRY positive pre-Sertoli cells in the gonad are probably more relevant than the postnatal proportion of the different mosaic clones. We discuss the dynamic nature of mitotic instability of isodicentric Y chromosomes and the fundamental role of Sertoli cells in gonadal differentiation and their contribution to the phenotypic variability. PMID- 20583183 TI - Hemifacial myohyperplasia sequence. AB - This is a report of an additional patient affected by hemifacial myohyperplasia (HMH). We postulate that this condition originates around the fourth gestational week at any step of cranial muscle development from somitomeres to branchial arches, most probably due to prolonged period of proliferation during cranial muscle development, subsequent abnormal contact between cranial neural crest (CNC) cells and cranial myoblasts, and an impaired interaction among CNC cells and cranial myoblasts derivatives. HMH may represent another example of somatic mosaicism and its features can be explained by a combination of morphostatic and morphodynamic mechanisms of pattern formation during development. Here we suggest that HMH is a sequence in which the primary defect is hyperplasia of the facial muscles and the other findings are secondary to this. PMID- 20583185 TI - Interstitial duplication in the proximal long arm of chromosome 16. PMID- 20583184 TI - Molecular characterization of a de novo 6q24.2q25.3 duplication interrupting UTRN in a patient with arthrogryposis. AB - Chromosome 6q duplications have been documented repeatedly, allowing the delineation of a "6q duplication syndrome," characterized by hypertelorism, downslanting palpebral fissures, tented upper lip, short neck, severe mental and growth retardation, and joint contractures. Most reported cases result from malsegregation of a reciprocal translocation leading to a terminal 6q duplication and partial monosomy of another chromosome. Only 11 cases of de novo pure duplication have been reported so far. The breakpoints do not appear to be recurrent, but in most cases they have not been characterized molecularly, precluding genotype-phenotype correlation. We report on an 8-year-old girl with a phenotype consistent with mild 6q duplication syndrome, including characteristic physical findings, mild mental retardation, and joint contractures. She carries a 13 Mb de novo 6q24.2q25.3 duplication, diagnosed by high-resolution karyotype and confirmed by array-CGH. Molecular characterization of the duplicated segment with quantitative PCR showed that the proximal breakpoint is localized within the UTRN gene, encoding utrophin, the autosomal homologue of dystrophin. We discuss the possible implication of UTRN in arthrogryposis associated with duplications spanning the 6q23q26 region. PMID- 20583186 TI - Karoly Mehes: Pioneer in the study of minor anomalies. A good and creative friend remembered. PMID- 20583187 TI - A user's guide to the elements of standard morphologic terminology: Analysis and database. PMID- 20583188 TI - Ruvalcaba syndrome revisited. PMID- 20583189 TI - New palpebral fissure measurements. PMID- 20583190 TI - The right to ignore genetic status of late onset genetic disease in the genomic era; Prenatal testing for Huntington disease as a paradigm. AB - During the last decade, the field of human genome research has gone through a phase of rapid discovery that has provided scientists and physicians with a wide variety of research tools that are applicable to important medical issues. We describe a true case of familial Huntington disease (HD) in which we modified personal details to protect patient's privacy, where the proband at risk preferred not to know his disease status but wanted to know the status in his unborn child. Once we found the father to be negative, the case raised an important ethical question regarding the management of this as well as future pregnancies. This article discusses the arguments for and against the right not to know of one's carrier status, as well as professional obligations in the context of withholding unwanted information that may have direct implications not only for the patient himself but also for other family members. HD has served as a model for many other adult onset genetic diseases in terms of carrier testing guidelines. Hence, we feel it is time to revisit the issue of prenatal testing for HD and consider updating the current recommendations regarding the patient's right to "genetic ignorance", or the right not to know genetic information. PMID- 20583191 TI - Cohesin biology and the cohesinopathies: Abstracts from the Second Biennial Conference, Pontignano, Italy, 2009. AB - The cohesin proteins compose an evolutionarily conserved complex whose fundamental role in chromosomal cohesion and coordinated segregation of sister chromatids has been well characterized across species. Recently regulators and structural components of cohesin have been found to surprisingly cause specific human developmental disorders (collectively termed "cohesinopathies") and some cancers when mutated. Since the first report of cohesin's role in regulating gene expression 10 years ago, there has been an explosion of literature implicating cohesin in multiple diverse cellular and gene regulatory processes. While downregulating cohesin sufficiently to cause significant sister chromatid cohesion defects is universally lethal to multicellular organisms, the mechanism of action by which cohesin effects developmental processes appears to be through a non-canonical role as a regulator of gene expression. It became evident that there was a need to bring cohesin basic scientists together with clinical investigators interested in the medical disorders associated with cohesin dysfunction to cross pollinate their fields and advance both the basic biology as well as the understanding of, and improved treatments for, this newly classified group of clinical disorders. Towards this end an international meeting hosted by the CNR in Italy and jointly supported by funds from the CdLS USA Foundation and the National Institute of Child Health and Development (NIH) was established in 2007. Based upon the success of that meeting a standing biennial meeting was established and the proceedings from the Second International Cohesin Biology and the Cohesinopathies Biennial Meeting held in Pontignano, Italy in 2009 are presented here. PMID- 20583192 TI - Effects of fermentation by lactic acid bacteria on the antigenicity of bovine whey proteins. AB - BACKGROUND: The main whey proteins alpha-lactalbumin (alpha-LA) and beta lactoglobulin (beta-LG) are considered as the major allergens in cow's milk. Microbial fermentation can produce some proteolytic enzymes, which can induce the degradation of milk protein allergens. In this study, the effects of fermentation by lactic acid bacteria on the antigenicity of alpha-LA and beta-LG were investigated using indirect competitive ELISA. Meanwhile, the proteolysis of milk proteins was detected by TNBS assay and SDS-PAGE electrophoresis. RESULTS: Fermentation by lactic acid bacteria could significantly reduce the antigenicity of alpha-LA and beta-LG in skim milk. Combined strains of Lactobacillus helveticus and Streptococcus thermophilus were the most effective in reducing the antigenicity of both whey proteins. In addition, alpha-LA and beta-LG antigenicity decreased to a lower value at 6 h of fermentation and at 0.5 d of cold storage by fermentation with the combined strains. The results of TNBS assay and SDS-PAGE electrophoresis showed that lactic acid bacteria strains used in this study hydrolysed whey proteins only to a limited extent. CONCLUSION: The fermentation with lactic acid bacteria is an effective way to reduce whey proteins antigenicity. PMID- 20583193 TI - Estimation of ruminal and intestinal digestion profiles, hourly effective degradation ratio and potential N to energy synchronization of co-products from bioethanol processing. AB - BACKGROUND: Little research has been conducted to determine the magnitude of the differences in nutritive value among wheat dried distillers' grains with solubles (DDGS), corn DDGS and blend DDGS, or between different bioethanol plants. The objectives of this study were to compare different types of DDGS and different bioethanol plants in terms of: (1) rumen degradation kinetics profile of each DDGS component and rumen availability; (2) intestinal digestion profile of rumen undegraded protein; (3) hourly effective rumen degradation ratio and potential N to-energy synchronization; (4) the role of acid detergent insoluble nitrogen in the determination of nutrient availability of DDGS. In addition, these parameters were compared in DDGS as opposed to parental grain. RESULTS: (1) The effective degradability of dry matter in DDGS samples increased as the content of feedstock wheat increased. DDGS are a good source of rumen-undegradable protein. The protein content of DDGS derived from wheat is higher relative to that derived from corn; however, the undegradability of the protein fraction increases as the proportion of corn in the feedstock augments. (2) In addition, DDGS provide significant amounts of rumen-degradable protein, which increased as the content of wheat in the feedstock increased. This indicates a potential loss of N when high levels of DDGS are included in the diet. (3) Acid detergent insoluble crude protein (ADICP) levels were low across DDGS samples, revealing no effect on ruminal and intestinal disappearance of protein. However, consideration should be given to the numerical differences in digestibility of rumen-undegradable protein and the relation to ADICP content. (4) Further research with a higher number of samples and higher variability in the ADICP content should be undertaken to investigate the effect of ADICP on rumen and intestinal disappearance of DDGS protein. CONCLUSION: The digestive characteristics of each DDGS component (dry matter, organic matter, crude protein and neutral detergent fiber), the hourly effective degradation ratio between N and organic matter, and the intestinal availability of rumen-undegradable protein differed significantly (P < 0.05) among wheat DDGS, blend DDGS and corn DDGS, and to a lesser extent between the different bioethanol plants. These results indicate that it is inappropriate to assume fixed rumen and intestinal degradation characteristics for DDGS without considering factors such as DDGS type and bioethanol plant origin. PMID- 20583194 TI - Toward small animal models for the study of human hepatitis viruses. PMID- 20583195 TI - Pre-"EMT"ing key processes in liver carcinogenesis: Growing evidence for how malignant hepatocytes invade and conquer. PMID- 20583197 TI - Diagnostic utility of chromosome 17 and p16 abnormalities in fluorescence in situ hybridization tests in primary sclerosing cholangitis. PMID- 20583198 TI - Methodological issues in a meta-analysis. PMID- 20583200 TI - Influence of degree of hydrolysis on functional properties and angiotensin I converting enzyme-inhibitory activity of protein hydrolysates from cuttlefish (Sepia officinalis) by-products. AB - BACKGROUND: In Tunisia the cuttlefish-processing industry generates large amounts of solid wastes. These wastes, which may represent 35% of the original material and constitute an important source of proteins, are discarded without any attempt at recovery. This paper describes some functional properties and the angiotensin I-converting enzyme (ACE)-inhibitory activity of protein hydrolysates prepared by hydrolysis of cuttlefish (Sepia officinalis) by-products with crude enzyme extract from Bacillus licheniformis NH1. RESULTS: Cuttlefish by-product protein hydrolysates (CPHs) with different degrees of hydrolysis (DH 5, 10 and 13.5%) were prepared. All CPHs contained 750-790 g kg(-1) proteins. Solubility, emulsifying capacity and water-holding capacity increased while fat absorption and foaming capacity decreased with increasing DH. All hydrolysates showed greater fat absorption than the water-soluble fraction from undigested cuttlefish by-product proteins and casein. CPHs were also analysed for their ACE-inhibitory activity. CPH3 (DH 13.5%) displayed the highest ACE inhibition (79%), with an IC(50) value of 1 mg mL(-1). CONCLUSION: Hydrolysis of cuttlefish by-product proteins with alkaline proteases from B. licheniformis resulted in a product with excellent solubility over a wide pH range and high ACE-inhibitory activity. This study suggests that CPHs could be utilised to develop functional foods for prevention of hypertension. PMID- 20583201 TI - Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance. AB - BACKGROUND: Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450-substrate interactions. RESULTS: Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X-ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also 'V'-shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT-CYP6G1 complex and a non-resistant CYP6A2 homology model implies that tight-fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin. CONCLUSION: The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities. PMID- 20583202 TI - Thrips (Thysanoptera: Thripidae) mitigation in seedling cotton using strip tillage and winter cover crops. AB - BACKGROUND: Thrips are the most consistent insect pests of seedling cotton in the southeastern United States, where symptoms can range from leaf curling to stand loss. In a 2 year study, thrips adults and immatures were sampled at 14, 21 and 28 days after planting on cotton planted with a thiamethoxam seed treatment in concert with crimson clover, wheat or rye winter cover crops and conventional or strip tillage to investigate potential differences in thrips infestations. RESULTS: Densities of adult thrips, primarily Frankliniella fusca (Hinds), peaked on the first sampling date, whereas immature densities peaked on the second sampling date. Regardless of winter cover crop, plots that received strip tillage experienced significantly fewer thrips at each sampling interval. In addition, assessment of percentage ground cover 42 days after planting showed that there was more than twice as much ground cover in the strip-tilled plots compared with conventionally tilled plots. Correlation analyses showed that increased ground cover was inversely related to thrips densities that occurred on all three sampling dates in 2008 and the final sampling date in 2009. CONCLUSIONS: Growers who utilize strip tillage and a winter cover crop can utilize seed treatments for mitigation of early-season thrips infestation. PMID- 20583203 TI - Hospitalization costs associated with warfarin-related bleeding events among older community-dwelling adults. AB - PURPOSE: A prior paper from this study demonstrated that patient report of receiving medication instructions from health care professionals is associated with reduced risk of warfarin-related bleeding hospitalizations. The objective of this analysis was to describe the hospitalization costs due to warfarin-related bleeding events in older community-dwelling adults and to estimate the hospitalization costs avoided due to the receipt of medication instruction from different sources. METHODS: We estimated the expected hospitalization costs associated with four instruction sources based on the respective incidence rate of observed hospitalizations and mean hospitalization cost for warfarin-related bleeding episodes from a prospective cohort study of beneficiaries of the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE). We estimated hospitalization costs avoided due to each instruction source compared to no instructions using the payer's perspective. We conducted probabilistic sensitivity analysis to account for uncertainty in our parameters. RESULTS: One hundred twenty-six warfarin-related bleeding hospitalizations occurred during the observation period with a mean cost of $10,819 (SD: $11,536). The mean expected hospitalization cost from a warfarin-related bleeding hospitalization without instruction was $835 per year per person. Hospitalization costs avoided with instruction from a health care professional ranged from $443 to $481 per year per person. CONCLUSIONS: The costs per hospitalization associated with warfarin related bleeding events are substantial. Instructions for warfarin management from a health care professional may reduce the number of warfarin-related bleeding hospitalizations and associated costs. Investments in interventions to improve communication regarding warfarin management may be justified economically based on the potential cost savings estimated in this study. PMID- 20583204 TI - Biosimilars: pharmacovigilance and risk management. AB - Biosimilars cannot be authorized based on the same requirements that apply to generic medicines. Despite the fact that the biosimilar and reference drug can show similar efficacy, the biosimilar may exhibit different safety profile in terms of nature, seriousness or incidence of adverse reactions. However, the data from pre-authorization clinical studies normally are insufficient to identify all potential differences. Therefore, clinical safety of similar biological medicinal products must be monitored closely on an ongoing basis during the post-approval phase including continued risk-benefit assessment. The biosimilar applicant must provide the European Medicines Agency (EMEA) with a risk management plan (EU-RMP) and pharmacovigilance programme with its application, including a description of the potential safety issues associated with the similar biological medicinal product that may be a result of differences in the manufacturing process from the reference biologic. The most critical safety concern relating to biopharmaceuticals (including biosimilars) is immunogenicity. Risk management applies scientifically based methodologies to identify, assess, communicate and minimise risk throughout a drug's life cycle so as to establish and maintain a favourable benefit-risk profile in patients. The risk management plan for biosimilars should focus on heightens the pharmacovigilance measures, identify immunogenicity risk and implement special post-marketing surveillance. Although International Nonproprietary Names (INNs) served as a useful tool in worldwide pharmacovigilance, for biologicals they should not be relied upon as the only means of product identification. Biologicals should always be commercialized with a brand name or the INN plus the manufacturer's name. PMID- 20583205 TI - The Tayside Stroke Cohort: exploiting advanced regional medical informatics to create a region-wide database for studying the pharmacoepidemiology of stroke. AB - PURPOSE: Observational studies can provide valuable information where data from randomised controlled trials is lacking. We aimed to generate a region-wide longitudinal register of stroke patients using record-linkage of existing clinical and research datasets. METHODS: The population were residents of Tayside, Scotland from 1994-2005. Stroke cases were identified from hospital inpatient admission records, death certificates and prescribing data. These were augmented with data derived from free-text CT-brain scan reports. Strokes were classified as intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or ischaemic stroke (IS). The methodology was validated by audit of patient case records. The incidence was calculated using direct standardisation to the standard European population for ages 45-84. Twenty-eight day case-fatality rates were calculated as percentages. RESULTS: There were 12 620 all-cause incident strokes (ICH 1057; SAH 511; IS 6257; undetermined 4795). Standardised incidences per 100 000 by subtypes of stroke were: ICH 35 (95%CI 33-38), SAH 19 (17-22) and IS 210 (205-217). The 28-day case-fatality rates were: ICH 49% (95%CI 46-52), SAH 38% (34-43) and IS 19% (18-20). Comparisons with previous studies were favourable for ICH and SAH. For IS the incidence was lower and fatality rate higher than elsewhere. Three hundred and three sets of patient case records were audited. The positive predictive value (PPV) for identifying cases of stroke was 94.7% (95%CI 91.6-96.7). CONCLUSIONS: The case ascertainment in the TSC compares favourably to established stroke cohorts. This cost effective resource can now be linked with multiple other clinical and research datasets in Tayside to further understanding of stroke and its treatment. PMID- 20583206 TI - Thiazolidinediones, cardiovascular disease and cardiovascular mortality: translating research into action for diabetes (TRIAD). AB - BACKGROUND: Studies have associated thiazolidinedione (TZD) treatment with cardiovascular disease (CVD) and questioned whether the two available TZDs, rosiglitazone and pioglitazone, have different CVD risks. We compared CVD incidence, cardiovascular (CV), and all-cause mortality in type 2 diabetic patients treated with rosiglitazone or pioglitazone as their only TZD. METHODS: We analyzed survey, medical record, administrative, and National Death Index (NDI) data from 1999 through 2003 from Translating Research Into Action for Diabetes (TRIAD), a prospective observational study of diabetes care in managed care. Medications, CV procedures, and CVD were determined from health plan (HP) administrative data, and mortality was from NDI. Adjusted hazard rates (AHR) were derived from Cox proportional hazard models adjusted for age, sex, race/ethnicity, income, history of diabetic nephropathy, history of CVD, insulin use, and HP. RESULTS: Across TRIAD's 10 HPs, 1,815 patients (24%) filled prescriptions for a TZD, 773 (10%) for only rosiglitazone, 711 (10%) for only pioglitazone, and 331 (4%) for multiple TZDs. In the seven HPs using both TZDs, 1,159 patients (33%) filled a prescription for a TZD, 564 (16%) for only rosiglitazone, 334 (10%) for only pioglitazone, and 261 (7%) for multiple TZDs. For all CV events, CV, and all-cause mortality, we found no significant difference between rosiglitazone and pioglitazone. CONCLUSIONS: In this relatively small, prospective, observational study, we found no statistically significant differences in CV outcomes for rosiglitazone- compared to pioglitazone-treated patients. There does not appear to be a pattern of clinically meaningful differences in CV outcomes for rosiglitazone- versus pioglitazone-treated patients. PMID- 20583207 TI - Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's disease. AB - PURPOSE: To estimate the risk (and determinants) of discontinuing cholinesterase inhibitors (ChEIs) in a population-based sample of Alzheimer's disease (AD) patients. METHODS: This is a retrospective cohort study based on linked de identified administrative health data from the province of Saskatchewan, Canada. The cohort included all AD patients receiving a ChEI prescription during the first year of provincial coverage (2000-2001). Persistence was defined as no gap of 60+ days between depletion and subsequent refill of a ChEI prescription. Kaplan-Meier analysis was used to estimate the risk of discontinuation over 40 months. Cox regression with time-varying covariates was used to assess risk factors for ChEI discontinuation. RESULTS: The sample included 1080 patients (64% female, average age 80 +/- 7 years). Baseline mean (SD) Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ) scores were 20.8 (4.4) and 17.5 (7.7), respectively. Over 40 months, 84% discontinued therapy. The 1-year risk of discontinuation was 66.4% (95%CI 63.5-69.3%). Discontinuation was significantly more likely for females (adjusted HR 1.34, 95%CI 1.16-1.55) and among those with lower MMSE scores (2.52, 2.01-3.17 if <15), not receiving social assistance (1.25, 1.07-1.45), and paying at least 65% of total prescription costs (1.51, 1.30-1.74). It was significantly less likely for patients with frequent physician visits (0.78, 0.66-0.93, for 7-19 vs. <7 visits), higher Chronic Disease Scores (0.74, 0.61-0.89, for 7+ vs. <4), and FAQ scores of 9+ (0.82, 0.69 0.99). CONCLUSION: The likelihood of discontinuing ChEI therapy was high in this real-world sample of AD patients. Significant predictors included clinical, socioeconomic, and practice factors. PMID- 20583208 TI - Antipsychotics and the risk of death in the elderly: an instrumental variable analysis using two preference based instruments. AB - PURPOSE: Observational studies have investigated the comparative safety of antipsychotics with varying results. Instrumental variable analysis has been suggested as a possible alternative to conventional analyses when there is concern about the effect of unmeasured confounding in observational studies. Using the example of the risk of death with typical compared to atypical antipsychotics, we aimed to explore the performance of two different instruments. We used the doctor prescribing preference instrument, which has been used in previous studies, to investigate further the assumptions of this instrument in the Australian population. We also propose an alternative instrument, nursing home facility preference. METHODS: With the Australian Department of Veterans' Affairs administrative claims database, we used an instrumental variable analysis to compare the risk of death after 12 months between the two antipsychotic classes. RESULTS: Using the doctor prescribing preference instrument we estimated that typical antipsychotics were associated with an extra 24 (95% Confidence Interval (CI) 18-30) deaths per 100 patients per year compared to atypical antipsychotics, and an extra 10 (95% CI 7-14) deaths per 100 patients per year among nursing home residents. Facility prescribing preference was a stronger instrument (OR=19.2 95% CI 17.1-21.6) and provided a better balance of covariates than doctor prescribing preference. CONCLUSIONS: Our study has shown that valid instruments in one population may not be directly applicable to other health care settings and testing of assumptions is crucial when performing IV analyses. Facility prescribing preference appears to be a potentially valid instrument for further work in this area. PMID- 20583209 TI - Factors associated with persistence of cholinesterase inhibitor treatments in the elderly. AB - PURPOSE: To identify factors associated with one-year persistence of cholinesterase inhibitor (ChI) treatments. METHODS: A retrospective cohort study was performed using the reimbursement database of the Echantillon Generaliste des Beneficiaires, a 1/96(e) representative sample of subjects affiliated to the French National Healthcare Insurance System. Among this, patients who initiated a ChI treatment between 1 January 2004 and 31 December 2005 and for whom 1 year of follow-up in the database after treatment initiation was available were identified. One-year persistence of ChI treatment was defined as an ongoing treatment without dispensing interval exceeding 60 consecutive days during the 12 months following treatment initiation. Drug switches were not considered as treatment discontinuation. A multivariate logistic regression was conducted to identify, among patients characteristics (sociodemographic, drug uses), factors associated with one-year persistence of ChI treatments. RESULTS: Among the 942 patients who initiated a treatment with ChI during the study period, 72.4% were women; mean age was 79.6 years (SD = 7.4). Patients used eight other different drugs in median (Inter-Quartile Range: 5-11); 63.7% used psychotropics, 63.6% used cardiovascular drugs. One-year persistence of ChI treatments was estimated at 45.3%. Persistence of ChI treatments was lower in patients aged 80 years and over (OR = 0.74, 95%CI: 0.57-0.96); it was higher in patients using antidepressants at ChI treatment initiation (OR = 1.38, 95%CI: 1.05-1.82). CONCLUSIONS: One-year persistence of ChI treatment was estimated at 45.3% in this French sample. To optimize persistence of ChI treatment in the demented, patients poorly symptomatic and/or aged over 80 years should be especially monitored. PMID- 20583210 TI - Conditional beta-catenin loss in mice promotes chemical hepatocarcinogenesis: role of oxidative stress and platelet-derived growth factor receptor alpha/phosphoinositide 3-kinase signaling. AB - Activation of beta-catenin, the central effector of the canonical Wnt pathway and a recognized oncogene, has been implicated in hepatocellular carcinoma. We examined N-nitrosodiethylamine (DEN)-induced tumorigenesis in hepatic beta catenin conditional knockout mice (beta-cat KO). Male beta-cat KO and age- and sex-matched littermate controls were given a single intraperitoneal DEN injection and followed for 6-12 months for hepatic tumors. Hepatic tumors were characterized for histology, proliferation, apoptosis, oxidative stress, and specific proteins by way of western blot, immunohistochemistry, and coprecipitation studies. For in vivo tumor intervention studies, specific inhibitors were administered intraperitoneally or through drinking water. Intriguingly, beta-cat KO mice showed a paradoxical increase in susceptibility to DEN-induced tumorigenesis. This accelerated tumorigenesis is due to increased injury and inflammation, unrestricted oxidative stress, fibrosis, and compensatory increase in hepatocyte proliferation secondary to platelet-derived growth factor receptor alpha (PDGFRalpha)/phosphoinositide 3-kinase (PIK3CA)/Akt activation and c-Myc overexpression. In vitro suppression of beta-catenin expression in hepatoma cells led to enhanced PDGFRalpha expression, which was abrogated in the presence of nuclear factor kappaB (NF-kappaB) inhibitor. Daily treatment of 6-month-old DEN-exposed beta-cat KO with PDGFRalpha inhibitor dramatically reduced tumor numbers and size. Inclusion of N-acetyl-L-cysteine, a known antioxidant and NF-kappaB inhibitor, in the drinking water led to complete abolition of tumorigenesis in DEN-exposed beta-cat KO. CONCLUSION: Loss of beta catenin impairs the liver's ability to counteract DEN-induced oxidative stress and enhances tumorigenesis through PDGFRalpha/PIK3CA/Akt signaling. Blockade of PDGFRalpha or oxidative stress dramatically affects beta-catenin-deficient tumorigenesis. Also, hepatoma cells use PDGFRalpha/PIK3CA signaling as an escape mechanism following beta-catenin suppression, and their sequential suppression profoundly impedes tumor proliferation. PMID- 20583211 TI - HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis. AB - Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 microg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 microg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 microg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH associated signs and symptoms was similar for C282Y homozygotes and HFE wild types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = -6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = -3%, 16%; P = 0.11). CONCLUSION: Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 microg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes. PMID- 20583212 TI - Transforming growth factor-beta induces senescence in hepatocellular carcinoma cells and inhibits tumor growth. AB - Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16(Ink4a)) are frequently inactivated in these cancers. We tested whether transforming growth factor-beta (TGF-beta) could serve as a potential senescence inducer in HCC. First, we screened for HCC cell lines with intact TGF-beta signaling that leads to small mothers against decapentaplegic (Smad)-targeted gene activation. Five cell lines met this condition, and all of them displayed a strong senescence response to TGF-beta1 (1-5 ng/mL) treatment. Upon treatment, c-myc was down regulated, p21(Cip1) and p15(Ink4b) were up-regulated, and cells were arrested at G(1). The expression of p16(Ink4a) was not induced, and the senescence response was independent of p53 status. A short exposure of less than 1 minute was sufficient for a robust senescence response. Forced expression of p21(Cip1) and p15(Ink4b) recapitulated TGF-beta1 effects. Senescence response was associated with reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) induction and intracellular reactive oxygen species (ROS) accumulation. The treatment of cells with the ROS scavenger N-acetyl-L-cysteine, or silencing of the NOX4 gene, rescued p21(Cip1) and p15(Ink4b) accumulation as well as the growth arrest in response to TGF-beta. Human HCC tumors raised in immunodeficient mice also displayed TGF-beta1-induced senescence. More importantly, peritumoral injection of TGF-beta1 (2 ng) at 4-day intervals reduced tumor growth by more than 75%. In contrast, the deletion of TGF-beta receptor 2 abolished in vitro senescence response and greatly accelerated in vivo tumor growth. CONCLUSION: TGF beta induces p53-independent and p16(Ink4a)-independent, but Nox4-dependent, p21(Cip1)-dependent, p15(Ink4b)-dependent, and ROS-dependent senescence arrest in well-differentiated HCC cells. Moreover, TGF-beta-induced senescence in vivo is associated with a strong antitumor response against HCC. PMID- 20583213 TI - "Nonalcoholic fatty liver disease" in a developing country: a different perspective. PMID- 20583214 TI - Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. AB - Beta-blockers may have a negative impact on survival in patients with cirrhosis and refractory ascites. The aim of this study was to evaluate the effect of the administration of beta-blockers on long-term survival in patients with cirrhosis and refractory ascites. We performed a single-center, observational, case-only, prospective study of patients with cirrhosis and refractory ascites who did or did not receive beta-blockers for the prevention of gastrointestinal bleeding; 151 patients were included. The mean Model for End-Stage Liver Disease score was 18.8 +/- 4.1. All patients regularly underwent large-volume paracentesis and intravenous albumin administration. Seventy-seven patients (51%) were treated with propranolol (113 +/- 46 mg/day). The median follow-up for the whole group was 8 months. The median survival time was 10 months [95% confidence interval (CI) = 8-12 months]. The probability of survival at 1 year was 41% (95% CI = 33% 49%). The clinical characteristics and laboratory values at enrolment were not significantly different between patients who were receiving propranolol and those who were not. The median survival time was 20.0 months (95% CI = 4.8-35.2 months) in patients not treated with propranolol and 5.0 months (95% CI = 3.5-6.5 months) in those treated with propranolol (P = 0.0001). The 1-year probability of survival was significantly lower in patients who received propranolol [19% (95% CI = 9%-29%)] versus those who did not [64% (95% CI = 52%-76%), P < 0.0001]. The independent variables of mortality were Child-Pugh class C, hyponatremia and renal failure as causes of refractory ascites, and beta-blocker therapy. CONCLUSION: The use of beta-blockers is associated with poor survival in patients with refractory ascites. These results suggest that beta-blockers should be contraindicated in these patients. PMID- 20583215 TI - A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with alpha1-antitrypsin deficiency. AB - Alpha(1)-antitrypsin is the most abundant circulating protease inhibitor. The severe Z deficiency allele (Glu342Lys) causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes. This causes neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. We have developed a conformation-specific monoclonal antibody (2C1) that recognizes the pathological polymers formed by alpha(1)-antitrypsin. This antibody was used to characterize the Z variant and a novel shutter domain mutant (His334Asp; alpha(1)-antitrypsin King's) identified in a 6-week-old boy who presented with prolonged jaundice. His334Asp alpha(1)-antitrypsin rapidly forms polymers that accumulate within the endoplasmic reticulum and show delayed secretion when compared to the wild-type M alpha(1)-antitrypsin. The 2C1 antibody recognizes polymers formed by Z and His334Asp alpha(1)-antitrypsin despite the mutations directing their effects on different parts of the protein. This antibody also recognized polymers formed by the Siiyama (Ser53Phe) and Brescia (Gly225Arg) mutants, which also mediate their effects on the shutter region of alpha(1)-antitrypsin. CONCLUSION: Z and shutter domain mutants of alpha(1) antitrypsin form polymers with a shared epitope and so are likely to have a similar structure. PMID- 20583216 TI - Micafungin: a brief review of pharmacology, safety, and antifungal efficacy in pediatric patients. AB - Invasive fungal infections are a major cause of morbidity and mortality in children with hematological malignancies and those undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). Although several new antifungal compounds recently became available, some are not yet approved for the use in the pediatric population. Among the new class of echinocandins, micafungin has been licensed in Europe and Japan for children including neonates. Because micafungin is well tolerated and exhibits few clinical relevant drug-drug interactions, the compound is of particular interest for prophylaxis and treatment of invasive mycoses in pediatric patients with cancer or following allogeneic HSCT. This review will focus on the currently available pediatric data of micafungin with emphasis on pharmacokinetics, efficacy, and safety. PMID- 20583217 TI - A new technique to stratify stroke risk in transient ischemic attack patients? PMID- 20583218 TI - Infections during induction therapy for children with acute lymphoblastic leukemia. the role of sulfamethoxazole-trimethoprim (SMX-TMP) prophylaxis. AB - BACKGROUND: Bacteremias are frequent during induction therapy for acute lymphoblastic leukemia (ALL) in children. Antibacterial prophylaxis therapy may thus be warranted. The purpose of this study was to analyze the rate of infections during induction therapy in two cohorts of children with ALL where one cohort received prophylactic sulfamethoxazole-trimethoprim (SMX-TMP). PROCEDURE: All infections were registered through a retrospective non-randomized review of medical records of 171 consecutive children newly diagnosed with ALL below 15 years of age at diagnosis. A total of 85 children treated from 1992 to 2000 did not receive SMX-TMP, whereas 86 children treated from 2000 to 2008 received SMX TMP 20 mg/kg in one daily oral dose during induction therapy. RESULTS: A total of 26% of all children had no febrile episodes during induction. Infections were more frequent in children below 5 years of age. Significantly fewer children receiving SMX-TMP developed fever (17% vs. 34%, P = 0.02) and bacteremia (20% vs. 45%, P = 0.0003). Especially children with non-high risk criteria had fewer infections when receiving prophylaxis. When adjusting for age, type of catheter, and SMX-TMP prophylaxis on the risk of bacteremia by a multiple Cox regression analysis, we found that age and prophylaxis, but not the type of catheter, were associated with a significantly reduced risk of bacteremia. CONCLUSION: Children with ALL receiving SMX-TMP prophylaxis during induction therapy experienced fewer febrile episodes, fewer days with fever demanding intravenous antibiotic treatment, and fewer episodes of bacteremia. Both SMX-TMP prophylaxis and age played significant independent roles for the occurrence of bacteremia. PMID- 20583219 TI - Perspectives of data analysis of enzyme inhibition and activation, part 4: equations for calculation of constants of enzyme activation and inhibition. AB - Equations for calculation of constants of enzyme activation and nontrivial types of enzyme inhibition, which are not reported in the literature, have been deduced. Examples of using these equations are also presented. PMID- 20583221 TI - Flexible residency program. PMID- 20583220 TI - Evaluation and management of pulmonary disease in ataxia-telangiectasia. AB - SUMMARY: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double-stranded DNA. The clinical phenotype is complex and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A-T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well-studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A-T are also outlined. PMID- 20583222 TI - Continuous dopaminergic therapy in Parkinson disease: time to stride back? PMID- 20583223 TI - Reply: Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy? PMID- 20583224 TI - Comparative effectiveness research in neurology: healthcare reform will increase the focus on finding the most effective--and affordable--treatment. PMID- 20583225 TI - NINDS common data element project: a long-awaited breakthrough in streamlining trials. PMID- 20583227 TI - 4-aminopyridine: new life for an old drug. PMID- 20583232 TI - Parathyroid gland preservation and selective autotransplantation utilizing topical lidocaine in total thyroidectomy. AB - OBJECTIVES/HYPOTHESIS: To review a new technique during total thyroidectomy that facilitates parathyroid gland preservation and selective autotransplantation utilizing topical 2% plain lidocaine as a spasmolytic/vasodilator agent. STUDY DESIGN: Retrospective case series review at a university hospital. METHODS: The study population comprised 100 consecutive patients (84 women and 16 men; mean age, 52 years) undergoing total thyroidectomy from January 2007 to December 2008. Interventions were: parathyroid glands (PGs) with signs of devascularization treated with a topical solution of 2% plain lidocaine in an attempt to restore blood flow before committing to autotransplantation. RESULTS: The main outcome measure was the incidence of hypoparathyroidism. A total of 40 parathyroid glands were autotransplanted. None of the 100 patients developed permanent hypoparathyroidism. There were no adverse effects utilizing this technique. CONCLUSIONS: In our experience, the use of lidocaine spasmolysis is a useful technique in thyroid surgery for salvaging devascularized PGs. Its utility as a selection method for PG autotransplantation incurs minimal risk or cost and might further reduce the incidence of permanent hypoparathyroidism. Further study is warranted. PMID- 20583233 TI - Second branchial fistula with unusual presentation--a case report. AB - Complete second branchial fistula is a rare clinical entity. The classical presentation of second branchial fistula is recurrent discharge from the external opening with or without recurrent painful neck swelling. We report an unusual case whose presenting symptom was a long-standing history of throat discomfort with recurrent blood stained saliva. Her symptoms resolved after her branchial fistula was excised. PMID- 20583234 TI - Does thyroid gland examination by palpation alter serum hormone levels? AB - OBJECTIVES/HYPOTHESIS: The goal of this study was to investigate the effects of routine thyroid gland palpation on serum thyroid hormone levels. STUDY DESIGN: Prospective study at Haydarpasa Numune Research and Education Hospital, Istanbul, Turkey. METHODS: This study was carried out in two groups with a total of 50 consecutive adults. Group I consisted of 20 patients (12 female and 8 male, aged 20-48 years) with a diagnosis of nodular thyroid disease confirmed by ultrasound imaging techniques. The second group consisted of 30 otherwise healthy subjects (17 female and 13 male, aged 18-50 years) referred for neck and thyroid ultrasound and with no thyroid pathology detected. Thyroid gland palpations were performed by the same physician. Blood samples were obtained before and 2 hours after thyroid gland palpation. Serum total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), and thyroglobulin (TG) measurements were made. RESULTS: We found that routine palpation in the first group caused a significant increase in serum TT3 (P < .05), FT3 (P < .01), FT4 (P < .05), and TG (P < .05) levels. In the second group, TT3 (P < .01), FT3 (P < .05), FT4 (P < .05), and TG (P < .05) levels also increased significantly after palpation. Differences in TSH and TT4 levels were not significant in any of the groups (P > .05). CONCLUSIONS: Preliminary data proposing a possible effect of routine thyroid gland palpation on serum thyroid hormone levels suggest that serum thyroid hormone measurements should be performed before any manipulation of the gland, including palpation, to avoid misdiagnosis. PMID- 20583235 TI - In reference to Advanced pediatric mastoiditis with and without intracranial complications. PMID- 20583237 TI - Airway obstruction and hemophilia-A: epiglottis hematoma. AB - Acute upper airway obstruction is a potentially life-threatening event. Hemophilia-A is a coagulopathy with high risk for spontaneous bleeding. Here we describe for the first time a spontaneous epiglottic internal hemorrhage leading to upper airway narrowing in a hemophilia-A patient. The patient was admitted to the intensive care unit for airway observation and treatment with factor VIII supplementation. In the first 48 hours there was rapid respiratory improvement. The epiglottic swelling resolved on the 5th day. In this patient no oral intubation or surgical management was needed. PMID- 20583241 TI - The effect of topical sodium thiosulfate in experimentally induced myringosclerosis. AB - OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the effect of topical sodium thiosulfate (STS) in experimentally induced myringosclerosis (MS). STUDY DESIGN: A prospective experimental animal study. METHODS: Thirty Wistar albino rats were bilaterally myringotomized. The right ears were treated with STS or saline daily, and the left ears were left untreated and used as controls. The tympanic membranes were observed by otoendoscopy weekly, and tympanometric measurements were performed. All animals were histopathologically examined for myringosclerotic plaques. RESULTS: Under otoendoscopy, myringosclerosis were observed around the handle of the malleus and near the annular region. The numbers of myringosclerotic ears were significantly more frequent in control and saline groups compared with the STS group (P < .05), and the formation of MS was more severe in control and saline groups compared with STS group (P < .05). Using tympanometric measurement, significantly reduced magnitudes of maximum admittance were observed in control and saline groups compared to normal and STS groups (P < .05). Under histopathologic examination, the tympanic membrane of the STS group appeared thinner than the control group (P < .05), with reduced calcium deposition than control and saline groups. CONCLUSIONS: Our results show that sodium thiosulfate has a preventive role in the development of myringosclerosis in the experimental animal model. PMID- 20583242 TI - Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: feasibility studies. AB - BACKGROUND AND OBJECTIVE: The main objective of the present study is to demonstrate the feasibility of utilizing a novel non-invasive radiofrequency (RF) device to induce lethal thermal damage to subcutaneous adipose tissue only by establishing a controlled electric field that heats up fat preferentially. STUDY DESIGN/MATERIALS AND METHODS: Adipocyte cells in six-well plates were subjected to hyperthermic conditions: 45, 50, 55, 60, and 65 degrees C during 1, 2, and 3 minutes. Cell viability was assessed 72 hours after exposure. Two groups of abdominoplasty patients were treated with the RF device during and days before their surgical procedure. Temperatures of cutaneous and subcutaneous tissues were measured during treatment (3 minutes) of the first group. The immediate tissue response to heating was assessed by acute histology. The delayed tissue response was assessed by histology analysis of the second group, 4, 9, 10, 17, and 24 days after treatment (22 minutes). A mathematical model was used to estimate treatment temperatures of the second group. The model uses patient-based diagnostic measurements as input and was validated with in vivo clinical temperature measurements. RESULTS: Cell viability dropped from 89% to 20% when temperature increased from 45 to 50 degrees C during 1 minute exposures. Three minutes at 45 degrees C resulted in 40% viability. In vivo, the temperature of adipose tissue at 7-12 mm depth from the surface increased to 50 degrees C while the temperature of cutaneous tissues was <30 degrees C during RF exposure. Acute and longitudinal histology evaluations show normal epidermal and dermal layers. Subcutaneous tissues were also normal acutely. Subcutaneous vascular alterations, starting at day 4, and fat necrosis, starting at day 9, were consistently observed within 4.5 19 mm depth from the skin surface. Subcutaneous tissue temperatures were estimated to be 43-45 degrees C for 15 minutes. CONCLUSIONS: A controlled internal electric field perpendicular to the skin-fat interface is selective in heating up fat and, consequently, has the ability to induce lethal thermal damage to subcutaneous adipose tissues while sparing overlying and underlying tissues. In vitro adipocyte cells are heat sensitive to thermal exposures of 50 and 45 degrees C on the order of minutes, 1 and 3 minutes, respectively. In vivo, 15 minutes thermal exposures to 43-45 degrees C result in a delayed adipocyte cellular death response-in this study, 9 days. The novel RF device presented herein effectively delivers therapeutic thermal exposures to subcutaneous adipose tissues while protecting epidermal and dermal layers. PMID- 20583243 TI - Temporal heating profile influence on the immediate bond strength following laser tissue soldering. AB - BACKGROUND: Bonding of tissues by laser heating is considered as a future alternative to sutures and staples. Increasing the post-operative bond strength remains a challenging issue for laser tissue bonding, especially in organs that have to sustain considerable tension or pressure. In this study, we investigated the influence of different temporal heating profiles on the strength of soldered incisions. The thermal damage following each heating procedure was quantified, in order to assess the effect of each heating profile on the thermal damage. MATERIALS AND METHODS: Incisions in porcine bowel tissue strips (1 cmx4 cm) were soldered, using a 44% liquid albumin mixed with indocyanine green and a temperature controlled laser (830 nm) tissue bonding system. Heating was done either with a linear or a step temporal heating profile. The incisions were bonded by soldering at three points, separated by 2 mm. Set-point temperatures of T(set) = 60, 70, 80, 90, 100, 110, 150 degrees C and dwell times of t(d) = 10, 20, 30, 40 seconds were investigated. The bond strength was measured immediately following each soldering by applying a gradually increased tension on the tissue edges until the bond break. RESULTS: Bonds formed by linear heating were stronger than the ones formed by step heating: at T(set) = 80 degrees C the bonds were 40% stronger and at T(set) = 90 degrees C the bonds strength was nearly doubled. The bond strength difference between the heating methods was larger as T(set) increased. CONCLUSION: Linear heating produced stronger bonds than step heating. The difference in the bond strength was more pronounced at high set-point temperatures and short dwell times. The bond strength could be increased with either higher set-point temperature or a longer dwell time. PMID- 20583244 TI - Optimization of the excimer laser assisted non-occlusive anastomosis (ELANA) flap retrieval rate. AB - BACKGROUND AND OBJECTIVES: A key element in the Excimer Laser Assisted Non occlusive Anastomosis (ELANA) technique is the retrieval of a disc ("flap") of artery wall from the anastomosis by the laser catheter tip. We assessed if the flap retrieval rate could be optimized. METHODS: We used a specially designed in vitro model using rabbit aortas. We tested three essential elements of the technique: (1) laser energy (10, 13, 15, or 18 mJ), (2) pressure on the catheter (0, 0.1, 0.2, or 0.4 N), and (3) number of lasing episodes (1 or 2). We made 2,280 anastomoses using different combinations of settings. With a logistic regression model we assessed the influence of each parameter. Current clinical settings (10 mJ, 0.2 N, 1 episode) were reference categories. RESULTS: Flap retrieval rate using conventional settings was 86.7%, equivalent to earlier reported clinical data. A significantly higher flap retrieval appeared when laser energy was increased to 13 mJ (OR 3.0, 95% CI 1.8-4.8), 15 mJ (OR 3.2, 95% CI 1.9 5.3), and 18 mJ (OR 3.7, 95% CI 2.2-6.2). A second lasing episode also significantly increased flap retrieval (OR 2.1, 95% CI 1.4-3.0). However, if we increased energy to 15 or 18 mJ, the effect of a second laser episode was insignificant. When the catheter was pushed down with 0.4 N, flap retrieval decreased significantly in all subgroups (OR 0.07, 95% CI 0.04-0.14). CONCLUSION: The flap retrieval of the ELANA anastomosis technique can be optimized to 100% by setting the laser energy at 15 mJ. However, safety studies are necessary before clinical application. A second lasing episode of 10 mJ is a good alternative to increase the flap retrieval. Moreover, the surgeon should be trained to apply not more than 0.2 N on the catheter. PMID- 20583245 TI - Assessment of tissue alteration in skin after interaction with photomechanical waves used for gene transfection. AB - BACKGROUND AND OBJECTIVE: We previously delivered a therapeutic gene to skin grafts of rats by using photomechanical waves (PMWs), also called laser-induced stress waves (LISWs), with the objective of enhancing adhesion of grafted tissue. The objective of this study was to evaluate tissue alterations that are possibly caused by PMWs used for gene delivery on the basis of immunohistochemistry and electron microscopy. MATERIALS AND METHODS: PMWs were generated by irradiating an elastic laser target (rubber disk) with 532 nm nanosecond laser pulses from a (of) Q-switched Nd:YAG laser. Tissue alterations were evaluated by histological analysis using hematoxylin and eosin (H&E) staining and immunohistochemical stainings, including anti-rat CD68 antibody staining to identify macrophages for detection of inflammation and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining for assessment of apoptosis. Morphological changes of cell membranes and organelles were evaluated by transmission electron microscopy. RESULTS: Skin exposed to PMWs that were generated at a laser fluence of 1.2 J/cm(2) (42 MPa in peak pressure), which is the optimum laser fluence (pressure) for therapeutic gene delivery to skin graft, showed no noticeable damage. At fluences higher than 1.8 J/cm(2) (>51 MPa), fragmentation of nuclei was observed and the number of CD68-positive cells increased remarkably. No significant increases in the numbers of TUNEL-positive keratinocytes and fibroblasts were observed at 1.2 J/cm(2). At fluences higher than 1.8 J/cm(2), the averaged ratio of TUNEL-positive cells also increased. The results of electron microscopy revealed that PMWs generated at 1.2 J/cm(2) caused neither damage to the cell membrane, nuclear membrane, or organelles. CONCLUSION: We observed no noticeable tissue alteration under the optimum laser irradiation conditions used for therapeutic gene delivery to a skin graft, demonstrating low invasiveness of our PMW-based gene transfection. PMID- 20583246 TI - Depth of tissue ablation and residual thermal damage caused by a pixilated 2,940 nm laser in a swine skin model. AB - BACKGROUND/OBJECTIVE: The purpose of this study was to assess the effects of fluence, pulse stacking, and multiple passes on the depth of injury caused by a fractionated Er:YAG laser in an in vivo farm pig model. DESIGN/MATERIAL/METHODS: A fractionated 2,940 nm Er:YAG laser (Pixel, Alma Lasers, Caesarea, Israel) was applied to the flank skin of a Yorkshire cross pig. The 11 mmx11 mm handpiece was comprised of either 49 or 81 microbeams (200 microm diameter), depending on the tip configuration. There were six different parameter sets divided according to total energy per pulse (150, 285, and 500 mJ) and tip type (81 or 49 microbeams per 11 mmx11 mm macrospot). Each of these six groups was subdivided according to number of stacked pulses (1, 3, and 6) and number of passes (1, 3, and 6). This resulted in a total of 36 treatment parameters. RESULTS: With the 49 microbeam configuration, a single pulse resulted in partial epidermal ablation at 150 mJ, complete epidermal ablation at 285 mJ and partial dermal ablation at 500 mJ to a depth of 90 microm. Stacking the pulses resulted in a significant increase in ablation with each fluence with the maximal depth of ablation measured at 140 microm after six stacked pulses at 500 mJ. Increasing the number of passes did not result in a significant increase in ablative depth, but did create a larger surface area of ablation. Residual thermal damage (RTD) was minimal and remained between 10 and 20 microm. CONCLUSIONS: The fractionated Er:YAG laser exhibited some of the same tissue interactions as its fully ablative counterparts. An increase in fluence resulted in an increase in ablative depth with minimal RTD. Additionally, RTD was unaffected by pulse stacking or by additional passes. Differences were that pulse stacking appeared to yield a more rapid decrease in ablation efficiency and additional passes did not seem to increase the depth of ablation. PMID- 20583248 TI - Increase in matrix metalloproteinase-2 level in the chicken retina after laser photocoagulation. AB - BACKGROUND AND OBJECTIVE: We investigated the levels of matrix metalloproteinase 2 (MMP-2), which has been implicated in various vitreoretinal diseases, in the retina after laser photocoagulation (LPC). MATERIALS AND METHODS: The time course of MMP-2 expression in 2-day-old chicken retinas before and 6 hours, 12 hours, 1 day, 2 days, 4 days, 8 days, 16 days, and 32 days after LPC was determined by real-time PCR and gelatin zymography. The basal level of MMP-2 in the retina and vitreous was also measured by gelatin zymography. MMP-2 localization in the retina was examined by immunohistochemistry. The localization of MMP-2 mRNA was determined by fluorescent in situ hybridization. The internal limiting membrane (ILM) was observed by scanning electron microscopy. RESULTS: MMP-2 mRNA expression in the retina peaked at day 4, but gelatin zymography showed that MMP 2 peaked 6 hours after LPC and the significant increase in the level of active MMP-2 lasted for more than 4 days. The concentration of MMP-2 in the vitreous was significantly higher than that in the retina. A distinct MMP-2 signal around the ILM was identified 6 hours after LPC, but MMP-2 mRNA was not detected there. Electron microscopy showed a damaged retinal surface after LPC. CONCLUSION AND OUTLOOK: The significant increase in retinal MMP-2 which lasted for more than 4 days after LPC may be induced by influx from the vitreous into the retina. This MMP-2 dynamics may contribute to pathological processes in the retina after LPC. PMID- 20583247 TI - A physical method to enhance transdermal delivery of a tissue optical clearing agent: combination of microneedling and sonophoresis. AB - BACKGROUND AND OBJECTIVES: Various physical methods, such as microneedling, laser ablation, sonophoresis, and sandpaper, have been widely studied to enhance the transdermal delivery of tissue optical clearing (TOC) agents. A previous study demonstrated that the microneedling method could effectively enhance the permeability of a TOC agent through the skin barrier. STUDY DESIGN/MATERIALS AND METHODS: In this study, we introduce a new physical combination method which utilizes both microneedling and sonophoresis to further enhance the transdermal delivery of a TOC agent, glycerol. Porcine skin samples were divided into a control group treated only with the microneedle roller and a test group treated with both the microneedle roller and sonophoresis. Glycerol was applied topically after microneedling. The optimal concentration and transdermal delivery efficacy of glycerol were quantitatively evaluated. RESULTS: A 70% glycerol solution was determined to be the optimal concentration for the combination method. The combination method resulted in approximately a 2.3-fold higher transdermal diffusion rate of glycerol when compared to the microneedling method alone. CONCLUSION: The combination method and optimal glycerol concentration effectively enhanced transdermal delivery of glycerol by accelerating the diffusion rate through the skin barrier. PMID- 20583249 TI - New technique using combined pulsed dye laser and fractional resurfacing for treating facial angiofibromas in tuberous sclerosis. AB - BACKGROUND AND OBJECTIVE: Tuberous sclerosis (TS) is a well-described genetic disorder that is classically associated with up to hundreds of facial angiofibromas. Due to the progressive nature of the skin lesions and the early clinical presentation, a safe and effective technique for treating these disfiguring skin lesions is needed. STUDY DESIGN/PATIENTS AND METHODS: We report a combinatorial technique for treating the angiofibromas of TS. We present a case series of three TS patients treated with this technique combining pinpoint electrosurgery, pulsed-dye laser treatment, and ablative fractional resurfacing (AFR). RESULTS: In all presented cases, improvement in the number and appearance of facial angiofibromas and erythema is noted. No scarring or adverse events were reported. CONCLUSION: The technique of electrosurgery, pulsed-dye laser treatment, and AFR represents a new and safe therapeutic option for treating facial angiofibromas associated with TS. PMID- 20583250 TI - Human liver autofluorescence: an intrinsic tissue parameter discriminating normal and diseased conditions. AB - BACKGROUND AND OBJECTIVE: Autofluorescence (AF) emission is an intrinsic parameter that can provide real-time information on morpho-functional properties of biological tissue, being strictly related with their biochemical composition and structural organization. The diagnostic potentials of AF-based techniques have been investigated on normal, fibrotic, and steatotic liver tissues, in reference to histological features as evidenced by specific histochemical stainings. MATERIALS AND METHODS: AF emission under excitation at 366 nm has been examined on cryostatic tissue sections obtained from biopsies collected during surgical operation, by means of fluorescence imaging and microspectrofluorometric techniques. RESULTS: NAD(P)H, collagen, and vitamin A were found to be the endogenous fluorophores characterizing normal, fibrotic, and steatotic liver tissue AF, respectively. The differences of their photo-physical properties, in terms of emission amplitude, spectral shape, and response to irradiation, give rise to modifications of overall AF signal collected from tissues that allow the liver conditions to be distinguished. CONCLUSION: The study provides a valid premise for a development of AF-based optical biopsy techniques for a real-time discrimination of liver anatomo-pathological patterns. PMID- 20583251 TI - Two-dimensional changes and surface characteristics from an erbium laser used for root canal preparation. AB - BACKGROUND AND OBJECTIVE: Erbium lasers have been advocated for use in root canal because of their ability to ablate dentin and remove biologic debris in the root canal space. This study evaluated the ability of an Er:YAG laser to remove dentin predictably in the root canal system and its cleaning ability. STUDY DESIGN/MATERIALS AND METHODS: Twenty-eight single-rooted extracted teeth were assigned into two groups. The first group was cleaned and shaped using crown-down technique with GT rotary files (control). The second group used an Er:YAG laser with ceramic tip, above the dentin ablation threshold for root canal shaping. A separate group of three teeth was evaluated for cleanliness using an Er:YAG laser with spiral tips. Amount of dentin removed in the buccal-lingual and mesial distal directions was measured, the data analyzed by ANOVA. Surface characteristics were qualitatively examined. RESULTS: The control group produced cleaner, better shaped root canals, faster than the Er:YAG group. The Er:YAG group removed more dentin in the coronal portion but less in the middle and apical thirds. The Er:YAG with spiral tip group left a dense smear layer in the middle and apical thirds. The Er:YAG group was subject to procedural errors more often than the control group. CONCLUSION: The Erbium laser studied was equivalent to rotary files in the coronal and middle thirds but not in the apical thirds of the root canal system. PMID- 20583252 TI - Photodynamic inactivation of Acinetobacter baumannii using phenothiazinium dyes: in vitro and in vivo studies. AB - BACKGROUND AND OBJECTIVE: Phenothiazinium dyes have been reported to be effective photosensitizers inactivating a wide range of microorganisms in vitro after illumination with red light. However, their application in vivo has not extensively been explored. This study evaluates the bactericidal activity of phenothiazinium dyes against multidrug-resistant Acinetobacter baumannii both in vitro and in vivo. STUDY DESIGN/MATERIALS AND METHODS: We report the investigation of toluidine blue O, methylene blue, 1,9-dimethylmethylene blue, and new methylene blue for photodynamic inactivation of multidrug-resistant A. baumannii in vitro. The most effective dye was selected to carry out in vivo studies using third-degree mouse burns infected with a bioluminescent A. baumannii strain, upon irradiation with a 652 nm noncoherent light source. The mice were imaged daily for 2 weeks to observe differences in the bioluminescence time curve between the photodynamic therapy (PDT)-treated mice in comparison with untreated burns. RESULTS: All the dyes were effective in vitro against A. baumannii after 30 J/cm(2) irradiation of 635 or 652 nm red light had been delivered, with more effective killing when the dye remained in solution. New methylene blue was the most effective of the four dyes, achieving a 3.2-log reduction of the bacterial luminescence during PDT in vivo after 360 J/cm(2) and an 800 microM dye dose. Moreover, a statistically significant reduction of the area under the bioluminescence-time curve of PDT-treated mice was observed showing that the infection did not recur after PDT. CONCLUSIONS: Phenothiazinium dyes, and especially new methylene blue, are potential photosensitizers for PDT to treat burns infected with multidrug-resistant A. baumannii in vivo. PMID- 20583253 TI - Photodynamic therapy selectively enhances liposomal doxorubicin uptake in sarcoma tumors to rodent lungs. AB - BACKGROUND: In specific conditions, photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial barrier in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We hypothesized that Visudyne(R)-mediated PDT could selectively increase liposomal doxorubicin (Liporubicin) uptake in sarcoma tumors to rodent lungs while sparing the normal surrounding tissue. MATERIALS AND METHODS: Sarcoma tumors were generated subpleurally in the left lower lung lobe of 66 Fischer rats. Ten days following sarcoma implantation, tumors underwent different pre-treatment schemes: no PDT (controls), low-dose PDT (0.0625 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)) and high-dose PDT (0.125 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)). Liporubicin was then administered and allowed to circulate for 1, 3, or 6 hours. At the end of each treatment scheme, we assessed the uptake of Liporubicin in tumor and lung tissues by high performance liquid chromatography and fluorescence microscopy. RESULTS: In all PDT-treated groups, there was a significant enhancement of Liporubicin uptake in tumors compared to controls after 3 and 6 hours of drug circulation. In addition, Liporubicin distribution within the normal lung tissue was not affected by PDT. Thus, PDT pre-treatment significantly enhanced the ratio of tumor-to-lung drug uptake compared to controls. Finally, fluorescence microscopy revealed a well detectable Liporubicin signaling throughout PDT-treated tumors but not in controls. CONCLUSIONS: PDT is a tumor-specific enhancer of Liporubicin distribution in sarcoma lung tumors which may find a translation in clinics. PMID- 20583254 TI - Mechanisms underlying early development of pulmonary vascular obstructive disease in Down syndrome: An imbalance in biosynthesis of thromboxane A2 and prostacyclin. AB - Patients with Down syndrome (DS) and a left-to-right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A(2) and prostacyclin (PGI(2)) in four groups of infants, cross-classified as shown below, by measuring the urinary excretion levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha): DS infants with a left-to-right shunt and PH (D-PH, n = 18), DS infants without congenital heart defect (D-C, n = 8), non-DS infants with a left-to-right shunt and PH (ND-PH, n = 12), and non-DS infants without congenital heart defect (ND-C, n = 22). The urinary excretion ratios of 11-dehydro-TXB(2) to 2,3-dinor-6-keto PGF(1alpha) in the D-PH, D-C, ND-PH, and ND-C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11-dehydro-TXB(2) to 2,3-dinor-6-keto PGF(1alpha) was higher in the presence of DS (P < 0.001), independently of the presence of PH (P = 0.297). The predominant biosynthesis of TXA(2) over PGI(2), leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left-to-right shunt. PMID- 20583255 TI - Analysis of cardiac development in the turtle Emys orbicularis (Testudines: Emidydae) using 3-D computer modeling from histological sections. AB - In this article we present a 3-D modeling study of cardiac development in the European pond turtle, Emys orbicularis (of the reptilian order Testudines). The study is aimed at elucidating the embryonic development of the horizontal septum in the ventricle and underscoring the importance of 3-D reconstructions in studying morphogenesis. Turtles possess one common ventricle, partly divided into three cava by a vertical and a horizontal septum, of which the embryonic origins have so far not been described. We used serial sectioning and computerized high resolution 3-D reconstructions of different developmental stages to create a chronological overview of cardiogenesis, in order to study this process. This has yielded a new understanding of the development of the horizontal septum and (directly related) the looping of the heart tube. This looping is found to be markedly different from that in the human heart, with the turtle having two clear bends in the part of the heart tube leaving the primitive ventricle, as opposed to one in humans. It is this particular looping that is responsible for the formation of the horizontal septum. In addition to our findings on the ventricular septation this study has also yielded new insights into the developmental origins of the pulmonary vein. The 3-D reconstructions were built using our platform TDR-3-D base and enabled us to study the developmental processes in specific parts of the turtle heart separately and in three dimensions, over time. The complete 3-D reconstructions have been made available to the reader via internet using our 3-D model browser application, which allows interactive viewing of the models. The browser application can be found on bio imaging.liacs.nl/galleries/emysorbicularis/TurtleGallery.html, along with additional images of both models and histological sections and animation sequences of the models. By allowing the reader to view the material in such an interactive way, we hope to make optimal use of the new 3-D reconstruction techniques and to engage the reader in a more direct manner. PMID- 20583256 TI - Hepatocyte growth factor induces invasion and migration of ovarian cancer cells by decreasing the expression of E-cadherin, beta-catenin, and caveolin-1. AB - Distant metastases are unusual occurrences at presentation and during the progression of epithelial ovarian cancer. There are no good clinical predictors of this phenomenon. In this study, we examined the role of hepatocyte growth factor (HGF) in cell metastasis in ovarian cancer HO8910 cells. We found that HGF has functions in biological processes essential to metastasis, including morphological remodeling, invasion and migration (P = 0.000, P = 0.001). Western blotting showed that in HGF treated group, the expression of E-cadherin, beta catenin, and caveolin-1 was decreased as compared with the control group (P = 0.000, P = 0.002, P = 0.000). Immunofluorescence staining demonstrated that the population of E-cadherin, beta-catenin, and caveolin-1 at the cell membrane was downregulated. Reverse transcriptase polymerase chain reaction analysis revealed the decreased expression of E-cadherin, beta-catenin, and caveolin-1 at the mRNA level. Our data indicated that HGF leads to downregulation of E-cadherin, beta catenin, and caveolin-1, disassembly of cell-cell contacts, and invasion and migration enhancement in human ovarian cancer cells. PMID- 20583257 TI - Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy. AB - Breast and prostate cancers are specially metastasizing to bone. Metastases from breast cancer usually exhibit a mixed osteolytic/osteosclerotic aspect, with osteolysis predominating. Osteosclerosis is a common finding in prostatic cancer although osteolysis occurs within the sclerotic lesions. B-cell malignancies (lymphoma, myeloma) are also associated with marked osteolysis. Histopathological examination of bone biopsies was used for the diagnosis of malignancies and, prior to embedding, microcomputed tomography (microCT) was done on the bone specimens. Patients (247) who presented either a bone metastasis, an overt myeloma, a lymphoma or a monoclonal gammopathy of undetermined significance were studied. All patients had a bone biopsy studied by 2D histomorphometry for the histopathology. During the fixation time, the bone cores were analyzed by microCT. On the 3D reconstructed models provided by microCT, signs of osteolysis/osteosclerosis were searched: excess of bone resorption, focal disorganization of microarchitecture, bone metaplasia, osteosclerosis. A strong agreement was obtained between histomorphometry and microCT results using Cohen's kappa test (kappa = 0.713). MicroCT identified excess bone resorption on trabecular surfaces when eroded surfaces were >10.5% by histomorphometry. MicroCT failed to identify some patients with smoldering myeloma or some lymphomas with microresorption. MicroCT data are obtained within 4 hr and suggest the malignant invasion of bone marrow when excess of bone resorption/formation is obtained. MicroCT can be used in the immediate postbiopsy period making possible a fast identification of malignancy. However these signs are not specific and must be confirmed by histopathological analysis. PMID- 20583258 TI - Developmental profile of claudin-3, -5, and -16 proteins in the epithelium of chick intestine. AB - Proteins in the claudin family are a main component of tight junctions and form a seal that modulates paracellular transport in intestinal epithelium. This research tests the hypothesis that claudins 3, 5, and 16 will appear in the epithelium of embryonic intestine during functional differentiation. Immunohistochemistry is utilized to explore the developmental patterns of claudin 3, -5, and -16 proteins in the epithelium of embryonic chick intestine from 9 days prior to hatching through the early post-hatch period. These claudin proteins either changed their cellular localization or first appeared around the time of hatching. After hatching, claudin-3 expression was prominent in basal lateral regions of the epithelium along the entire villus, but was absent from crypts. Claudin-5 was expressed most strongly in the crypt and lower villus epithelium within junctional complexes, whereas immunostaining of claudin-16 was localized within goblet cells of the upper villus region. The relative mRNA levels of claudin-3, -5, and -16 showed similar patterns; transcript levels rose between 18 and 20 days of development, then dropped by 2 days post-hatch. Results of this work indicate that the claudin proteins assume their final locations within the epithelium around the time of hatching, suggesting that in addition to their known barrier and fence functions within tight junctions, these claudins may have additional roles in the differentiation and/or physiological function of chick intestine. The localization of claudin-16 to goblet cells and its distribution in the more mature cells of the upper villus region suggest an unexpected role in goblet cell maturation and mucus secretion. PMID- 20583259 TI - The anatomy of the gastrointestinal tract of the African lungfish, Protopterus annectens. AB - The gastrointestinal tract of the African lungfish Protopterus annectens is a composite, which includes the gut, the spleen, and the pancreas. The gut is formed by a short oesophagus, a longitudinal stomach, a pyloric valve, a spiraling intestine, and a cloaca. Coiling of the intestine begins dorsally below the pylorus, winding down to form six complete turns before ending into the cloaca. A reticular tissue of undisclosed nature accompanies the winding of the intestinal mucosa. The spleen is located along the right side of the stomach, overlapping the cranial end of the pancreas. The pancreas occupies the shallow area, which indicates on the gut dorsal side the beginning of the intestine coiling. In addition, up to 25 lymphatic-like nodes accompany the inner border of the spiral valve. The mesenteric artery forms a long axis for the intestine. All the components of the gastrointestinal tract are attached to each other by connective sheaths, and are wrapped by connective tissue, and by the serosa externally. We believe that several previous observations have been misinterpreted and that the anatomy of the lungfish gut is more similar among all the three lungfish genera than previously thought. Curiously, the gross anatomical organization is not modified during aestivation. We hypothesize that the absence of function is accompanied by structural modifications of the epithelium, and are currently investigating this possibility. PMID- 20583260 TI - Enhancement of P-glycoprotein expression by hepatocyte transplantation in carbon tetrachloride-induced rat liver. AB - The multidrug resistance protein P-glycoprotein (P-gp) is physiologically expressed at the bile canalicular membrane of the liver, where it participates in the biliary excretion of various lipophilic drugs. Chronic exposure to carbon tetrachloride (CCI(4)) is known to induce hepatic fibrosis resulting in hepatotoxicity. This study focuses on the effects of CCI(4) and hepatic transplantation (HT) on the P-gp expressions in rat liver. Male SD rats were treated with CCI(4) to induce liver damage for 3, 7, 14, 21, and 28 days, respectively. Immunohistochemistry revealed that P-gp was widely distributed in the liver and was spread from the cytoplasm to cell membrane of the rat liver. Western blot showed remarkable increase of P-gp expression in 3 days CCI(4) treated rats, whereas, a continuous decrease in the P-gp expression was seen in 7, 14, 21, and 28 days CCI(4)-treated rats. After HT with cells from the normal rat liver, the level of P-gp increased comparing with those from the sham operation. Blood biochemistry showed decreased levels of serum alanine transaminase, aspartate transaminase, and alkaline phosphatase and increased serum levels of triglyceride and total protein, which indicated the improved function of the liver damaged by CCI(4). These results illustrate the variation of the expression of P-gp in CCI(4)-induced hepatic damage and an increase of P gp level after HT in the toxic liver induced by CCI(4). We hypothesized that P-gp may play a protective role in the process of liver injury. HT can be beneficial to ameliorate the rat liver functional damage induced by CCI(4). PMID- 20583261 TI - Onset of apoptosis in the cystic duct during metamorphosis of a Japanese lamprey, Lethenteron reissneri. AB - A nonparasitic lamprey in Japan, Lethenteron reissneri, stops feeding prior to the commencement of metamorphosis. Resumption of feeding cannot take place due to major alterations in the digestive system, including loss of the gall bladder (GB) and biliary tree in the liver. This degeneration of bile ducts is considered to depend on programmed cell death or apoptosis, but molecular evidence of apoptosis remains lacking. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and immunohistochemistry with an antibody against active caspase-3, we showed that epithelial cells of the cystic duct (CD) and GB became TUNEL-positive by the early metamorphosing stage. Immunohistochemical staining of active caspase-3, a key mediator in the apoptotic cascade, showed that the apoptotic signal was initiated in the region around the CD in the late larval phase. In later stages, active caspase-3-positive epithelial cells were also observed in the large intrahepatic bile duct (IHBD) and peripheral small IHBDs. At the early metamorphosing stage, bile canaliculi between hepatocytes were dilated and displayed features resembling canaliculi in cholestasis. Onset of apoptosis around the CD, which is the pathway for the storage of bile juice, and progression of apoptosis towards the large IHBD, which is the pathway for the secretion of bile juice, may lead to temporary intrahepatic cholestasis. The present study represents the first precise spatial and temporal analysis of apoptosis in epithelial cells of the biliary tract system during metamorphosis of any lamprey species. PMID- 20583262 TI - Ontogenetic scaling of caudal fin shape in Squalus acanthias (Chondrichthyes, Elasmobranchii): a geometric morphometric analysis with implications for caudal fin functional morphology. AB - The shark heterocercal caudal fin and its contribution to locomotion are of interest to biologists and paleontologists. Current hydrodynamic data show that the stiff dorsal lobe leads the ventral lobe, both lobes of the tail are synchronized during propulsion, and tail shape reflects its overall locomotor function. Given the difficulties surrounding the analysis of shark caudal fins in vivo, little is known about changes in tail shape related to ontogeny and sex in sharks. A quantifiable analysis of caudal fin shape may provide an acceptable proxy for inferring gross functional morphology where direct testing is difficult or impossible. We examined ontogenetic and sex-related shape changes in the caudal fins of 115 Squalus acanthias museum specimens, to test the hypothesis that significant shape changes in the caudal fin shape occur with increasing size and between the sexes. Using linear and geometric morphometrics, we examined caudal shape changes within the context of current hydrodynamic models. We found no statistically significant linear or shape difference between sexes, and near isometric scaling trends for caudal dimensions. These results suggest that lift and thrust increase linearly with size and caudal span. Thin-plate splines results showed a significant allometric shape change associated with size and caudal span: the dorsal lobe elongates and narrows, whereas the ventral lobe broadens and expands ventrally. Our data suggest a combination of caudal fin morphology with other body morphology aspects, would refine, and better elucidate the hydrodynamic factors (if any) that underlie the significant shape changes we report here for S. acanthias. PMID- 20583263 TI - Muscle architecture in the mystacial pad of the rat. AB - The vibrissal system of the rat is an example of active tactile sensing, and has recently been used as a prototype in construction of touch-oriented robots. Active vibrissal exploration and touch are enabled and controlled by musculature of the mystacial pad. So far, knowledge about motor control of the rat vibrissal system has been extracted from what is known about the vibrissal systems of other species, mainly mice and hamsters, since a detailed description of the musculature of the rat mystacial pad was lacking. In the present work, the musculature of the rat mystacial pad was revealed by slicing the mystacial pad in four different planes, staining of mystacial pad slices for cytochrome oxidase, and tracking spatial organization of mystacial pad muscles in consecutive slices. We found that the rat mystacial pad contains four superficial extrinsic muscles and five parts of the M. nasolabialis profundus. The connection scheme of the three parts of the M. nasolabialis profundus is described here for the first time. These muscles are inserted into the plate of the mystacial pad, and thus, their contraction causes whisker retraction. All the muscles of the rat mystacial pad contained three types of skeletal striated fibers (red, white, and intermediate). Although the entire rat mystacial pad usually functions as unity, our data revealed its structural segmentation into nasal and maxillary subdivisions. The mechanisms of whisking in the rat, and hypotheses concerning biomechanical interactions during whisking, are discussed with respect to the muscle architecture of the rat mystacial pad. PMID- 20583264 TI - Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression. AB - Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA induced thermal hyperalgesia of rats. PMID- 20583266 TI - Histochemical and ultrastructural observations of respiratory epithelium and gland in yak (Bos grunniens). AB - Submucous glands and epithelial mucous cells of yak (Bos grunniens) respiratory tract have been studied by a variety of histochemical methods and transmission electron microscopy for differentiating and characterizing serous and mucous cells. By light microscopy, the distribution, numbers of mucous cells, volume of mucous glands (Reid index), and the ratio of mucous cell to serous cell in the bronchial tree were measured with different staining. Histochemically, a majority of mucous cells, presented in the surface epithelium of bronchi and glands, secreted neutral and acid mucosubstances, only a few sulfated mucosubstances were present. No mucus-producing cells were observed from the terminal to respiratory bronchiolar level. Ultrastructurally, serous cells in glands of the lamina propria had two distinct forms: one type filled with many round dense secretory granules, plentiful RER and few other organelles, similar to other animals; the other type contained some oval mitochondrial and distended RER, the granules resembled the former. The mucous cells in gland were similar to that of epithelium, which containing abundant secretory granules with an eccentric core. The mucous cells of the surface epithelium differ from other animals in the structure and histochemistry of their secretory granules. Analysis of the size and distribution of the secretory granules and other organelles of serous cells suggested that differences represent different phases of a secretory cycle, not various populations of cell or granules. PMID- 20583267 TI - Quantitative computed tomography of humpback whale (Megaptera novaeangliae) mandibles: mechanical implications for rorqual lunge-feeding. AB - Rorqual whales (Balaenopteridae) lunge at high speed with mouth open to nearly 90 degrees to engulf large volumes of prey-laden water. This feeding process is enabled by extremely large skulls and mandibles that increase mouth area, thereby facilitating the flux of water into the mouth. When these mandibles are lowered during lunge-feeding, they are exposed to high drag, and therefore, may be subject to significant bending forces. We hypothesized that these mandibles exhibited a mechanical design (shape and density distribution) that enables these bones to accommodate high loads during lunge-feeding without exceeding their breaking strength. We used quantitative computed tomography (QCT) to determine the three-dimensional geometry and density distribution of a pair of subadult humpback whale (Megaptera novaeangliae) mandibles (length = 2.10 m). QCT data indicated highest bone density and cross-sectional area, and therefore, high resistance to bending and deflection, from the coronoid process to the middle of the dentary, which then decreased towards the anterior end of the mandible. These results differ from the caudorostral trends of increasing mandibular bone density in mammals, such as humans and the right whale, Eubalaena glacialis, indicating that adaptive bone remodeling is a significant contributing factor in establishing mandibular bone density distributions in rorquals. PMID- 20583265 TI - Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex. AB - Fibroblast growth factor-23 (FGF23) is a hormone that modulates circulating phosphate (P(i)) levels by controlling P(i) reabsorption from the kidneys. When FGF23 levels are deficient, as in tumoral calcinosis patients, hyperphosphatemia ensues. We show here in a murine model that Fgf23 ablation disrupted morphology and protein expression within the dentoalveolar complex. Ectopic matrix formation in pulp chambers, odontoblast layer disruption, narrowing of periodontal ligament space, and alteration of cementum structure were observed in histological and electron microscopy sections. Because serum P(i) levels are dramatically elevated in Fgf23(-/-), we assayed for apoptosis and expression of members from the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, both of which are sensitive to elevated P(i) in vitro. Unlike X-linked hypophosphatemic (Hyp) and wild-type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23(-/-) specimens. Further, in comparison to Hyp and WT samples, decreased bone sialoprotein and elevated dentin matrix protein-1 protein levels were observed in cementum of Fgf23(-/-) mice. Additional dentin-associated proteins, such as dentin sialoprotein and dentin phosphoprotein, exhibited altered localization in both Fgf23(-/-) and Hyp samples. Based on these results, we propose that FGF23 and (P(i)) homeostasis play a significant role in maintenance of the dentoalveolar complex. PMID- 20583268 TI - Histological and ultrastructural characterization of developing miniature pig salivary glands. AB - Salivary glands are a classic model of organ development and differentiation. Miniature pigs are considered as a unique animal model for salivary gland researchers in the fields of gene transfer, radiation damage, and functional reconstruction. However, there is little information about the development of miniature pig salivary glands. The present article was designed to study the developmental stages of salivary glands in miniature pigs using histological and ultrastructural methods. Sections from E40, E60, E80, E95 embryos, and P0 pups were stained with hematoxylin-eosin, Alcian blue, or periodic acid-schiff. Selected specimens were also processed for electron microscopy. The development of the miniature pig salivary glands can be divided into five different stages that refer to the stages of the developing mouse submandibular gland. The histological characteristics of the miniature pig salivary glands at different developmental stages were synchronously verified at the ultrastructural level. Interestingly, the development of the miniature pig parotid gland trailed that of the submandibular gland by approximately 15 days. Our study provides first-hand data regarding the morphological organogenesis of salivary glands in the miniature pig and provides a foundation for further research on this model. PMID- 20583269 TI - Histomorphology of the penis bone (Baculum) in the gray long-eared bat Plecotus austriacus (Chiroptera, Vespertilionidae). AB - For the first time, the histomorphology of the penis bone of a bat (Plecotus austriacus) was examined in detail. From Plecotus austriacus, 14 whole penes and 11 isolated bacula were studied and compared to bacula of Plecotus auritus and Plecotus macrobullaris. The baculum was located on specimen microradiographs and in micro-CT images in the tip of the penis. Using serial semithin sections and surface-stained, undecalcified ground sections, the types of bone and other tissues constituting the baculum were examined by light microscopy. 3D reconstructions were generated from the serial semithin sections and from micro CT images. The shaft and the proximal branches of the Y-shaped baculum form a tubular bone around a medullary cavity. Since the small diameter of this channel and the main lamellar bone around it resemble a Haversian canal, the baculum is equivalent to a single-osteon bone. Several oblique nutrient canals enter this medullary cavity in the shaft and branches. All ends of the baculum consist predominantly of woven bone. The collagen fiber bundles of the tunica albuginea of both corpora cavernosa insert via fibrocartilage into the woven bone of the branches. Thus, the microscopic structures support the hypothesis that the baculum functions as a stiffening element in the erect penis. In this study, several microscopic imaging techniques were evaluated for displaying the microscopic structures of the baculum. Specimen microradiography, but especially micro-CT proved to be suitable nondestructive methods for accurate and reproducible demonstration and comparison of the three-dimensional structures of the baculum in different bat species. PMID- 20583270 TI - Whole blood flow cytometric measurement of NFATc1 and IL-2 expression to analyze cyclosporine A-mediated effects in T cells. AB - The calcineurin inhibitor Cyclosporine A (CsA) is one of the crucial immunosuppressive drugs given after organ transplantation. The small therapeutic window of CsA generates the dilemma that efficient and toxic drug doses differ only slightly. Moreover, these threshold concentrations differ considerably between individuals; therefore, functional assays are urgently needed. We explored whether the transcription factor NFATc1, a direct as well as indirect target of CsA, can be used as a potential biomarker to determine the individual immunosuppressive activity of CsA. First, in isolated human T cells we showed that flow cytometry is practicable to measure NFATc1, the most abundant NFATc isoform in activated T cells. Second, for whole blood we developed a flow cytometric assay to determine in parallel the inducible transcription factor NFATc1 and the cytokine IL-2 in stimulated T cells. We found that added CsA inhibits both the expression of NFATc1 and IL-2 in T cells of stimulated whole blood samples with IC(50) values of 200 and 150 nM, respectively. The intra- and inter-assay variability was low, and clinical practicability was good. Further experiments have to demonstrate whether the parallel cytometric measurement of NFATc1 and IL-2 in whole blood is a good predictor of individual CsA efficacy and toxicity in CsA-treated patients. PMID- 20583272 TI - Cytometry and single cell analysis: 30 years of coevolution. PMID- 20583273 TI - Neuron tracing in perspective. AB - The study of the structure and function of neuronal cells and networks is of crucial importance in the endeavor to understand how the brain works. A key component in this process is the extraction of neuronal morphology from microscopic imaging data. In the past four decades, many computational methods and tools have been developed for digital reconstruction of neurons from images, with limited success. As witnessed by the growing body of literature on the subject, as well as the organization of challenging competitions in the field, the quest for a robust and fully automated system of more general applicability still continues. The aim of this work, is to contribute by surveying recent developments in the field for anyone interested in taking up the challenge. Relevant aspects discussed in the article include proposed image segmentation methods, quantitative measures of neuronal morphology, currently available software tools for various related purposes, and morphology databases. (c) 2010 International Society for Advancement of Cytometry. PMID- 20583274 TI - Data analysis in flow cytometry: the future just started. AB - In the last 10 years, a tremendous progress characterized flow cytometry in its different aspects. In particular, major advances have been conducted regarding the hardware/instrumentation and reagent development, thus allowing fine cell analysis up to 20 parameters. As a result, this technology generates very complex datasets that demand for the development of optimal tools of analysis. Recently, many independent research groups approached the problem by using both supervised and unsupervised methods. In this article, we will review the new developments concerning the use of bioinformatics for polychromatic flow cytometry and propose what should be done to unravel the enormous heterogeneity of the cells we interrogate each day. PMID- 20583276 TI - Microfluidic impedance-based flow cytometry. AB - Microfabricated flow cytometers can detect, count, and analyze cells or particles using microfluidics and electronics to give impedance-based characterization. Such systems are being developed to provide simple, low-cost, label-free, and portable solutions for cell analysis. Recent work using microfabricated systems has demonstrated the capability to analyze micro-organisms, erythrocytes, leukocytes, and animal and human cell lines. Multifrequency impedance measurements can give multiparametric, high-content data that can be used to distinguish cell types. New combinations of microfluidic sample handling design and microscale flow phenomena have been used to focus and position cells within the channel for improved sensitivity. Robust designs will enable focusing at high flowrates while reducing requirements for control over multiple sample and sheath flows. Although microfluidic impedance-based flow cytometers have not yet or may never reach the extremely high throughput of conventional flow cytometers, the advantages of portability, simplicity, and ability to analyze single cells in small populations are, nevertheless, where chip-based cytometry can make a large impact. PMID- 20583275 TI - Good cell, bad cell: flow cytometry reveals T-cell subsets important in HIV disease. AB - Flow cytometry is a key technology in the study of HIV disease. In this article, we review various cellular markers that can be measured in the setting of pathogenesis or vaccination studies, including markers of activation, differentiation, senescence, immune suppression, and function. In addition, we discuss important considerations for making these measurements. Finally, we examine how flow cytometry studies have taught researchers about the disease process, and the potential for flow cytometry technology to guide treatment decisions and evaluate vaccine candidates in the future. PMID- 20583277 TI - Nuclear genome size: are we getting closer? AB - Correct information on genome size is important in many areas of research. For a long time, scientists have been struggling to understand the reason for the huge variation in eukaryotic genome size and its biological significance. More recently, the knowledge on genome size has become important to structure genome sequencing projects as their scale and cost depend on genome size. Despite the fact that the first estimates of genome size in eukaryotes were made more than 50 years ago, we are still not quite sure about the exact genome size in practically all animal and plant species. Moreover, different estimates continue to be published for the same species. These discrepancies compromise data comparison and interpretation and point to methodological problems, which include standardization. This article assesses the current state of DNA reference standards for flow cytometry and the issues related to their calibration. PMID- 20583279 TI - Small but mighty: how the MACS-technology based on nanosized superparamagnetic particles has helped to analyze the immune system within the last 20 years. AB - Today, magnetic cell sorting and flow cytometric cell sorting both are state-of the-art technologies, with a plethora of applications in biology and biomedicine. Both technologies have their stand-alone applications, but they also perfectly complement each other, in particular for the analysis and isolation of fragile and rare cells. The technological evolution from simple magnets and steel wool separation columns to sophisticated instrumentation and automated procedures has paved the way for magnetic cell separation in the scientific community. This review will focus on applications of magnetic cell sorting with commercially available paramagnetic MACS(R)-nanoparticles (Miltenyi Biotech, Bergisch Gladbach, Germany) that have allowed unprecedented approaches to the exploration of the immune system in basal and clinical research of humans and rodents. Thus, during the last 20 years this technology has been continuously developed so that the widest array of leukocyte subsets, stem cells, and connective tissue cells can be addressed by MACS(R)-conjugated antibodies directed against cell-specific surface antigens or secreted cytokines for research and clinical applications. PMID- 20583280 TI - Viability states of bacteria--specific mechanisms of selected probes. AB - Single cell techniques like flow cytometry combined with viability staining can help to obtain information on viability states of bacteria. Many fluorescent dyes are available for this purpose and can be chosen according to the available excitation source, the species used, and the background of scientific questions and relevant specifications. Within this short overview, we focus on two diverse groups of bacteria: the gram- Escherichia coli and representatives of the gram+ Mycobacterium to demonstrate differences and similarities in dye uptake principles, processing and binding. We call for attention to possible diverse responses of different species to various viability assays. The cell surface structure of bacteria and the chemical properties of fluorescent probes considerably determine the success of a certain staining practice. Particular focus was drawn on analysis of membrane integrity, uptake of substrates and transformation of fluorogenic substrates. PMID- 20583281 TI - Is length an appropriate estimator to characterize pulmonary alveolar capillaries? A critical evaluation in the human lung. AB - Stereological estimations of total capillary length have been used to characterize changes in the alveolar capillary network (ACN) during developmental processes or pathophysiological conditions. Here, we analyzed whether length estimations are appropriate to describe the 3D nature of the ACN. Semi-thin sections of five human lungs, previously investigated by Gehr et al. (Respir Physiol 1978; 32:121-140), were used to estimate alveolar capillary length using a "design-based" or a "model-based" stereological approach. The design-based approach involves counting of capillary profiles related to a defined area of the reference space. The model-based approach bases on the assumption that capillaries are round tubes and length was calculated from capillary volume and surface area. The model-based approach provided a mean of 6,950 km (SD: 3,108 km) for total capillary length, the design-based approach resulted in a mean of 2,746 km (SD: 722 km). Because of the geometry of the ACN both approaches carry an unpredictable bias. The bias incurred by the design-based approach is proportional to the ratio between radius and length of the capillary segments in the ACN, the number of branching points and the winding of the capillaries. The model-based approach is biased because of the real noncylindrical shape of capillaries and the network structure. In conclusion, the estimation of the total length of capillaries in the ACN cannot be recommended as the geometry of the ACN does not fulfill the requirements for stereological length estimation. Until new methods are being developed, the unbiased estimates of capillary volume, and surface area should be preferred. PMID- 20583284 TI - Using cases to strengthen inference on the association between single nucleotide polymorphisms and a secondary phenotype in genome-wide association studies. AB - Case-control genome-wide association studies provide a vast amount of genetic information that may be used to investigate secondary phenotypes. We study the situation in which the primary disease is rare and the secondary phenotype and genetic markers are dichotomous. An analysis of the association between a genetic marker and the secondary phenotype based on controls only (CO) is valid, whereas standard methods that also use cases result in biased estimates and highly inflated type I error if there is an interaction between the secondary phenotype and the genetic marker on the risk of the primary disease. Here we present an adaptively weighted (AW) method that combines the case and control data to study the association, while reducing to the CO analysis if there is strong evidence of an interaction. The possibility of such an interaction and the misleading results for standard methods, but not for the AW or CO approaches, are illustrated by data from a case-control study of colorectal adenoma. Simulations and asymptotic theory indicate that the AW method can reduce the mean square error for estimation with a prespecified SNP and increase the power to discover a new association in a genome-wide study, compared to CO analysis. Further experience with genome-wide studies is needed to determine when methods that assume no interaction gain precision and power, thereby can be recommended, and when methods such as the AW or CO approaches are needed to guard against the possibility of nonzero interactions. PMID- 20583283 TI - Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. AB - Cell culture studies and animal models point to an important role of oxidative/nitrosative stress in the pathogenesis of cerebral ammonia toxicity. However, it is unknown whether oxidative/nitrosative stress in the brain is also characteristic of hepatic encephalopathy (HE) in humans. We therefore analyzed post mortem cortical brain tissue samples from patients with cirrhosis dying with or without HE in comparison with brains from patients without liver disease. Significantly elevated levels of protein tyrosine-nitrated proteins, heat shock protein-27, and 8-hydroxyguanosine as a marker for RNA oxidation were found in the cerebral cortex of HE patients, but not of patients with cirrhosis but without HE. Glutamine synthetase (GS) activity was significantly decreased, whereas GS protein expression was not significantly affected. Protein expression of the glutamate/aspartate cotransporter was up-regulated in HE, whereas protein expression of neuronal and inducible nitric oxide synthases, manganese-dependent and copper/zinc-dependent superoxide dismutase, and glial glutamate transporter-1 were not significantly increased. CONCLUSION: These data indicate that HE in patients with cirrhosis is associated with oxidative/nitrosative stress, protein tyrosine nitration, and RNA oxidation, suggesting a role of oxidative stress in the pathogenesis of HE in patients with cirrhosis. PMID- 20583285 TI - Bayesian mixture models for the incorporation of prior knowledge to inform genetic association studies. AB - In the last decade, numerous genome-wide linkage and association studies of complex diseases have been completed. The critical question remains of how to best use this potentially valuable information to improve study design and statistical analysis in current and future genetic association studies. With genetic effect size for complex diseases being relatively small, the use of all available information is essential to untangle the genetic architecture of complex diseases. One promising approach to incorporating prior knowledge from linkage scans, or other information, is to up- or down-weight P-values resulting from genetic association study in either a frequentist or Bayesian manner. As an alternative to these methods, we propose a fully Bayesian mixture model to incorporate previous knowledge into on-going association analysis. In this approach, both the data and previous information collectively inform the association analysis, in contrast to modifying the association results (P-values) to conform to the prior knowledge. By using a Bayesian framework, one has flexibility in modeling, and is able to comprehensively assess the impact of model specification on posterior inferences. We illustrate the use of this method through a genome-wide linkage study of colorectal cancer, and a genome-wide association study of colorectal polyps. PMID- 20583286 TI - An "almost exhaustive" search-based sequential permutation method for detecting epistasis in disease association studies. AB - Due to the complex nature of common diseases, their etiology is likely to involve "uncommon but strong" (UBS) interactive effects--i.e. allelic combinations that are each present in only a small fraction of the patients but associated with high disease risk. However, the identification of such effects using standard methods for testing association can be difficult. In this work, we introduce a method for testing interactions that is particularly powerful in detecting UBS effects. The method consists of two modules--one is a pattern counting algorithm designed for efficiently evaluating the risk significance of each marker combination, and the other is a sequential permutation scheme for multiple testing correction. We demonstrate the work of our method using a candidate gene data set for cardiovascular and coronary diseases with an injected UBS three locus interaction. In addition, we investigate the power and false rejection properties of our method using data sets simulated from a joint dominance three locus model that gives rise to UBS interactive effects. The results show that our method can be much more powerful than standard approaches such as trend test and multifactor dimensionality reduction for detecting UBS interactions. PMID- 20583287 TI - Analyze multivariate phenotypes in genetic association studies by combining univariate association tests. AB - Multivariate phenotypes are frequently encountered in genome-wide association studies (GWAS). Such phenotypes contain more information than univariate phenotypes, but how to best exploit the information to increase the chance of detecting genetic variant of pleiotropic effect is not always clear. Moreover, when multivariate phenotypes contain a mixture of quantitative and qualitative measures, limited methods are applicable. In this paper, we first evaluated the approach originally proposed by O'Brien and by Wei and Johnson that combines the univariate test statistics and then we proposed two extensions to that approach. The original and proposed approaches are applicable to a multivariate phenotype containing any type of components including continuous, categorical and survival phenotypes, and applicable to samples consisting of families or unrelated samples. Simulation results suggested that all methods had valid type I error rates. Our extensions had a better power than O'Brien's method with heterogeneous means among univariate test statistics, but were less powerful than O'Brien's with homogeneous means among individual test statistics. All approaches have shown considerable increase in power compared to testing each component of a multivariate phenotype individually in some cases. We apply all the methods to GWAS of serum uric acid levels and gout with 550,000 single nucleotide polymorphisms in the Framingham Heart Study. PMID- 20583288 TI - Liver graft procurement in donors with central nervous system cancers. PMID- 20583289 TI - Evaluating the power to discriminate between highly correlated SNPs in genetic association studies. AB - Neighboring common polymorphisms are often correlated (in linkage disequilibrium (LD)) as a result of shared ancestry. An association between a polymorphism and a disease trait may therefore be the indirect result of a correlated functional variant, and identifying the true causal variant(s) from an initial disease association is a major challenge in genetic association studies. Here, we present a method to estimate the sample size needed to discriminate between a functional variant of a given allele frequency and effect size, and other correlated variants. The sample size required to conduct such fine-scale mapping is typically 1-4 times larger than required to detect the initial association. Association studies in populations with different LD patterns can substantially improve the power to isolate the causal variant. An online tool to perform these calculations is available at http://moya.srl.cam.ac.uk/ocac/FineMappingPowerCalculator.html. PMID- 20583290 TI - Recurrent low gamma-glutamyl transpeptidase cholestasis following liver transplantation for bile salt export pump (BSEP) disease (posttransplant recurrent BSEP disease). AB - Bile salt export pump (BSEP) deficiency is a hereditary cholestatic syndrome that results from mutations in the ABCB11 (ATP-binding cassette B11) gene. Severely affected patients develop end-stage liver disease in the first decade of life. Liver transplantation has traditionally been thought of as curative for BSEP disease. We describe the clinical course of 6 patients who developed recurrent low gamma-glutamyl transpeptidase cholestasis, that mimicks BSEP disease, following transplantation. All had documented genetic defects in ABCB11 that were predicted to lead to a congenital absence of BSEP protein. The time to development of recurrence was variable; 4 underwent repeat liver transplantation for complications of recurrent disease and all 4 again developed recurrent disease after retransplantation. Siblings of these patients who also underwent liver transplantation for BSEP disease have not developed "recurrent" disease. Three of the patients with "recurrent" disease ultimately died, 2 as a direct result of complications of their liver disease. PMID- 20583291 TI - Acute lower respiratory tract infections by human metapneumovirus in children in Southwest China: a 2-year study. AB - Human metapneumovirus (hMPV) has been reported to cause both upper and lower respiratory tract diseases in susceptible populations, particularly in children and the elderly. In this study, we describe a hospital-based epidemiological study of hMPV in patients presenting to a children's hospital and show the demographic and clinical characteristics associated with hMPV infection in China, retrospectively. Specimens were collected over a 2-year period from children hospitalized with acute lower respiratory tract infections (ALRTI) and analyzed for the presence of hMPV using real-time RT-PCR assays. The presence of hMPV was detected in 227 (25.9%) of the 878 children studied and may circulate year-round in the area, peaking during the winter-spring season. Younger children (aged less than 6 months) had the highest positive rate. Infections by hMPV showed similar epidemiology and clinical manifestations as for respiratory syncytial virus (RSV) and were found in high co-infections with RSV. Subgroup A2 hMPV was the most predominant genotype identified during the study period. This study indicates that hMPV is one of the major respiratory pathogens found in children in southwest China and vaccine development should be under consideration. PMID- 20583292 TI - Dornase alfa improves the health-related quality of life among Brazilian patients with cystic fibrosis--a one-year prospective study. AB - SUMMARY BACKGROUND: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. PATIENTS AND METHODS: One hundred fifty six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T(0)), and at 3 (T(1)), 6 (T(2)), 9 (T(3)), and 12 (T(4)) months of follow-up. Eighteen patients were excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. RESULTS: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T(4) - T(0) = 8.1; 95% confidence interval (95% CI) = [2.1;14.0]; effect size (ES) = 0.35; P < 0.001), Emotional Functioning (T(4) - T(0) = 5.6; 95% CI = [1.1;10.1]; ES = 0.31; P < 0.05), Social Functioning (T(4) - T(0) = 6.0; 95% CI = [1.3;11.7]; ES = 0.31; P < 0.05), Body Image (T(4) - T(0) = 11.9; 95% CI = [4.1;19.7]; ES = 0.42; P < 0.05), and Treatment Burden (T(4) - T(0) = 5.3; 95% CI = [0.3;10.3]; ES = 0.24; P < 0.05) domains in the younger group. A significant improvement in Role Functioning (T(4) - T(0) = 6.1; 95% CI = [1.1;11.1]; ES = 0.40; P < 0.05), Body Image (T(4) - T(0) = 12.6; 95% CI = [3.5;21.7]; ES = 0.46; P < 0.05), and Weight (T(4) - T(0) = 11.7; 95% CI = [1.8;21.6]; ES = 0.40; P < 0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T(4) - T(0) = 5.5; 95% CI = [1.5;9.4]; ES = 0.30; P < 0.05), Respiratory Symptoms (T(4) - T(0) = 7.6; 95% CI = [3.9;11.4]; ES = 0.48; P < 0.05), and Weight (T(4) - T(0) = 10.1; 95% CI = [1.6;18.6]; ES = 0.26; P < 0.05) domains. CONCLUSION: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment. PMID- 20583293 TI - Free radical-scavenging activity and DNA damaging potential of auxins IAA and 2 methyl-IAA evaluated in human neutrophils by the alkaline comet assay. AB - Auxins, of which indole-3-acetic acid (IAA) is the most widespread representative, are plant hormones. In addition to plants, IAA also naturally occurs in humans in micromolar concentrations. In the presence of peroxidase, indolic auxins are converted to cytotoxic oxidation products and have thus been proposed for use in gene-directed enzyme/prodrug tumor therapy. Since data on the genotoxicity of IAA and its derivatives are not consistent, here we investigate the early DNA damaging effects (2-h treatment) of the auxins, IAA, and 2-methyl indole-3-acetic acid (2-Me-IAA) by the alkaline comet assay and compare them with their free radical-scavenging activity measured by the 2,2-diphenyl-1 picrylhydrazyl (DPPH) assay. Human neutrophils are chosen as the test system since they possess inherent peroxidase activity. The results of the comet assay indicate an increase in DNA damage in a dose-dependent manner up to 1.00 mM of both auxins. Generally, IAA applied in the same concentration had greater potential to damage DNA in human neutrophils than did 2-Me-IAA. The genotoxicities of the two examined auxins are negatively correlated with their antioxidant activities, as measured by the DPPH assay; 2-Me-IAA showed a higher antioxidant capacity than did IAA. We assume that differences in the molecular structure of the tested auxins contributed to differences in their metabolism, in particular, with respect to interactions with peroxidases and other oxidative enzymes in neutrophils. However, the exact mechanisms have to be elucidated in future studies. PMID- 20583295 TI - First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function. AB - Sclerosteosis is a rare bone dysplasia characterized by greatly increased bone mass, especially of the long bones and the skull. Patients are tall, show facial asymmetry and often have syndactyly. Clinical complications are due to entrapment of cranial nerves. The disease is thought to be due to loss-of-function mutations in the SOST gene. The SOST gene product, sclerostin, is secreted by osteocytes and transported to the bone surface where it inhibits osteoblastic bone formation by antagonizing Wnt signaling. In a small Turkish family with sclerosteosis, we identified a missense mutation (c.499T>C; p.Cys167Arg) in exon 2 of the SOST gene. This type of mutation has not been previously reported and using different functional approaches, we show that it has a devastating effect on the biological function of sclerostin. The affected cysteine is the last cysteine residue of the cystine-knot motif and loss of this residue leads to retention of the mutant protein in the ER, possibly as a consequence of impaired folding. Together with a significant reduced ability to bind to LRP5 and inhibit Wnt signaling, the p.Cys167Arg mutation leads to a complete loss of function of sclerostin and thus to the characteristic sclerosteosis phenotype. PMID- 20583294 TI - ADHD prevalence and association with hoarding behaviors in childhood-onset OCD. AB - BACKGROUND: It has been suggested that attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), both neurodevelopmental disorders with onset in childhood, are highly comorbid, but previous studies examining ADHD and OCD comorbidity have been quite variable, partly because of inconsistency in excluding individuals with tic disorders. Similarly, ADHD has been postulated to be associated with hoarding although this potential relationship is largely methodologically unexplored. This study aimed to examine the prevalence of ADHD among individuals with childhood-onset OCD but without comorbid tic disorders, as well as to examine the relationship between clinically significant hoarding behaviors (hoarding) and ADHD. METHOD: ADHD prevalence rates and the relationship between ADHD and hoarding were examined in 155 OCD-affected individuals (114 probands and 41 relatives, age range 4-82 years) recruited for genetic studies and compared to pooled prevalence rates derived from previously published studies. RESULTS: In total, 11.8% met criteria for definite ADHD, whereas an additional 8.6% had probable or definite ADHD (total=20.4%). In total, 41.9% of participants with ADHD also had hoarding compared to 29.2% of participants without ADHD. Hoarding was the only demographic or clinical variable independently associated with ADHD (odds ratio=9.54, P<0.0001). CONCLUSION: ADHD rates were elevated in this sample of individuals with childhood-onset OCD compared to the general population rate of ADHD, and there was a strong association between ADHD and clinically significant hoarding behavior. This association is consistent with recent studies suggesting that individuals with hoarding may exhibit substantial executive functioning impairments and/or abnormalities, including attentional problems. PMID- 20583297 TI - Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. AB - The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of type 1 (slow twitch) fibers compared to type 2 (fast twitch) fibers. To investigate whether mutations in RYR1 are a cause of CFTD we sequenced RYR1 in seven CFTD families in whom the other known causes of CFTD had been excluded. We identified compound heterozygous changes in the RYR1 gene in four families (five patients), consistent with autosomal recessive inheritance. Three out of five patients had ophthalmoplegia, which may be the most specific clinical indication of mutations in RYR1. Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1 are a relatively common cause of CFTD and can be associated with extreme fiber size disproportion. PMID- 20583298 TI - Neurodevelopmental effects of prenatal exposure to psychotropic medications. AB - Until now, studies on the reproductive safety of psychotropics have typically assessed the risk of congenital malformations and perinatal complications associated with in utero exposure to such medications. However, little is known of their inherent potential neurobehavioral teratogenicity. The objective is to analyze available data from studies investigating developmental outcome of children exposed prenatally to psychotropics. A computerized Medline/PubMed/TOXNET/ENBASE search (1960-2010) was conducted using the following keywords: pregnancy, child/infant development/neurodevelopment, antidepressants, benzodiazepines, mood stabilizers, and antipsychotics. A separate search was also run to complete the safety profile of single specific medications. Resultant articles were cross-referenced for other relevant articles not identified in the initial search. A noncomputerized review of pertinent journals and textbooks was also performed. All studies published in English and reporting primary data on the developmental outcome of infants exposed in utero to psychotropics and born without malformations were collected. As regards antiepileptic drugs, only studies that provided data on specific medications approved for psychiatric practice use (carbamazepine, lamotrigine, and valproate) were considered. Data were extracted from 41 articles (38 identified electronically and 3 nonelectronically), which met the inclusion criteria. Despite reviewed studies showing relevant methodological limitations, concordant, albeit preliminary, information seems to exclude that prenatal exposure to both selective serotonin reuptake inhibitors and tricyclic antidepressants may interfere with the infants' psychological and cognitive development. Conversely, information on valproate strongly discourages its use in pregnant women. Moreover, although data on carbamazepine remain controversial, information on whole classes of drugs and single medications is either absent (second-generation antipsychotics) or too limited (first-generation antipsychotics, benzodiazepines, lithium, and lamotrigine) to inform the decision-making process. For all classes of psychotropics, new and/or further studies are warranted to answer definitively the urgent question about the impact of prenatal exposure to such medications on infant development. PMID- 20583299 TI - Functional analysis of the HGSNAT gene in patients with mucopolysaccharidosis IIIC (Sanfilippo C Syndrome). AB - Mucopolysaccharidosis (MPS) IIIC is an autosomal recessive lysosomal storage disorder caused by a deficiency in heparan acetyl CoA: alpha-glucosaminide N acetyltransferase (HGSNAT). The characteristic feature is the deterioration of the central nervous system, but other symptoms may include coarse facies, developmental delay, macrocrania and motor retardation. HGSNAT is localised to the lysosomal membrane and catalyses a transmembrane acetylation in which the terminal glucosamine residue of heparan sulphate acquires an acetyl group, thus forming N-acetylglucosamine. 54 variants of the HGSNAT gene have been identified in MPS IIIC patients thus far, 22 of which are missense mutations. In this study, 20 of the latter were introduced into the cDNA of HGSNAT, and the resultant derivatives were exogenously expressed in cell culture. Transfection of 16 of these resulted in the synthesis of negligible HGSNAT protein and activity. The levels and function of the remaining 4 mutants, however, were similar to those of exogenously expressed wild-type HGSNAT. Interestingly, c.1209G>T (p.W403C), which is present in a variant classified in the former category, has only been sequenced in alleles also possessing c.1843G>A (p.A615T), which independently has a negligible effect on HGSNAT expression. This report suggests that these may function together to abolish HGSNAT activity. PMID- 20583300 TI - Antioxidant liposomes protect against CEES-induced lung injury by decreasing SAF 1/MAZ-mediated inflammation in the guinea pig lung. AB - We reported earlier in a guinea pig model that exposure of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog, causes lung injury associated with the activation of tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinases (MAPK) signaling, and activator protein-1 (AP-1) transcription factor. Our earlier studies also revealed that antioxidant liposomes can be used as antidotes. Proinflammatory cytokines IL-1, IL-6, and TNF-alpha, either alone or in combination, can induce the activation of another group of transcription factors, namely SAF-1 (serum accelerator factor-1)/MAZ (Myc-associated zinc finger protein). Phosphorylation of SAF-1 via MAPK markedly increases its DNA binding and transactivational potential. The objective of the present study was to investigate whether CEES exposure causes activation of IL-1 beta, IL-6, and SAF-1/MAZ and whether these effects can be prevented by antioxidant liposomes. A single dose (200 microL) of the antioxidant liposome mixture was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed either 1 h or 30 days after CEES exposure. CEES exposure caused an upregulation of proinflammatory cytokines IL-6 and IL-1 beta in the lung along with an increase in the activation of transcription factor SAF-1/MAZ. The antioxidant liposomes treatment significantly blocked the CEES-induced activation of IL-6, IL-1 beta, and SAF-1/MAZ. This might suggest that antioxidant liposomes might offer a potential therapeutic strategy against inflammatory diseases associated with activation of these bioactive molecules. PMID- 20583301 TI - PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit. AB - Mutation of the human prion protein gene (PRNP) open reading frame (ORF) accounts for almost all reported familial concurrence of prion disease. The more common mutations globally: octapeptide repeat insertions, P102L, D178N, E200K, and V210I have occurred in large multigenerational pedigrees and display autosomal dominant inheritance, however, many rare genetic changes have been reported that are of uncertain pathogenicity. Based on 19 years of PRNP sequencing at the MRC Prion Unit, London, and analysis of 3664 samples from patients referred with suspected prion disease and healthy populations, we present novel allele combinations, healthy control population data, results of screening the PRNP ORF in DNA from the entire referral series and the CEPH human genome diversity cell line panel. Of the 10 alleles detected in patients for which detailed cases histories are presented, 4 are unreported (G54S, D167N, V209M, Q212PP), two changes are thought to be pathogenic but have not been described in our regions (P105L from the UK, G114V from India and Turkey), and the remainder reported in healthy control populations or in trans to known pathogenic mutations suggesting non- or low pathogenicity (G54S, 1-OPRI, G142S, N171S, V209M, E219K). New genotype-phenotype correlations and population frequencies presented will help the diagnosis and genetic counselling of those with suspected inherited prion disease. PMID- 20583302 TI - LPIN1 gene mutations: a major cause of severe rhabdomyolysis in early childhood. AB - Autosomal recessive LPIN1 mutations have been recently described as a novel cause of rhabdomyolysis in a few families. The purpose of the study was to evaluate the prevalence of LPIN1 mutations in patients exhibiting severe episodes of rhabdomyolysis in infancy. After exclusion of primary fatty acid oxidation disorders, LPIN1 coding sequence was determined in genomic DNA and cDNA. Among the 29 patients studied, 17 (59%) carried recessive nonsense or frameshift mutations, or a large scale intragenic deletion. In these 17 patients, episodes of rhabdomyolysis occurred at a mean age of 21 months. Secondary defect of mitochondrial fatty oxidation or respiratory chain was found in skeletal muscle of two patients. The intragenic deletion, c.2295-866_2410-30del, was identified in 8/17 patients (47%), all Caucasians, and occurred on the background of a common haplotype, suggesting a founder effect. This deleted human LPIN1 form was unable to complement Delta pah1 yeast for growth on glycerol, in contrast to normal LPIN1. Since more than 50% of our series harboured LPIN1 mutations, LPIN1 should be regarded as a major cause of severe myoglobinuria in early childhood. The high frequency of the intragenic LPIN1 deletion should provide a valuable criterion for fast diagnosis, prior to muscle biopsy. PMID- 20583303 TI - Synthesis and characterization of a Hyaluronan-polyethylene copolymer for biomedical applications. AB - Hyaluronan (HA)-based biomaterials are of interest for bone and cartilage tissue engineering because HA plays an important role in orthopedic tissue development, function, and repair. The goal of this project was to develop a biomaterial that incorporated the constituents of both a hydrogel and a hydrophobic polymer for biomedical applications. A series of amphiphilic graft copolymers consisting of HA, a glycosaminoglycan, and high-density polyethylene (HDPE), that is, HA-co HDPE, were fabricated. The chemical characteristics, physical and viscoelastic properties, and cytocompatibility of novel HA-co-HDPE materials were characterized via Fourier Transform infrared (FTIR) spectroscopy, solid state nuclear magnetic resonance (ssNMR) spectroscopy, differential scanning calorimetry (DSC), dynamic shear testing, and an in vitro human osteoblast cell study. The esterification reaction between HA and functionalized HDPE resulted in semicrystalline, insoluble powder. The dynamic shear properties of HA-co-HDPE concentrated solutions were more like natural proteoglycans than the HA control. HA-co-HDPE was successfully compression molded into disks that swelled upon hydration. Osteoblasts were viable and expressed the osteoblast phenotype after 7 days of culture on HA-co-HDPE materials. These HA-co-HDPE materials may have several biomaterial applications in saline suspension or molded form, including orthopedic tissue repair. PMID- 20583304 TI - Characterization of protein degradation in serum-based lubricants during simulation wear testing of metal-on-metal hip prostheses. AB - A size exclusion high performance liquid chromatography (SEC-HPLC) method has been developed which is capable of separation and quantitation of bovine serum albumin (BSA) and bovine serum globulin (BSG) components of serum-based lubricant (SBL) solutions. This allowed characterization of the stability profiles of these proteins when acting as lubricants during hip wear simulation, and identification of wear-specific mechanisms of degradation. Using cobalt-chromium metal-on-metal (MOM) hip joints, it was observed that BSA remained stable for up to 3 days (215K cycles) of wear testing after which the protein degraded in a fairly linear fashion. BSG on the other hand, began to degrade immediately and in a linear fashion with a rate constant of 5% per day. Loss of both proteins occurred via the formation of high molecular weight aggregates which precipitated out of solution. No fragmentation of the polypeptide backbone of either protein was observed. Data obtained suggest that protein degradation was not due to microbial contamination, denaturation at the air-water interface, or frictional heating of articulating joint surfaces in these studies. We conclude that the primary source of protein degradation during MOM simulation testing occurs via high shear rates experienced by SBL solutions at articulating surfaces, possibly coupled with metal-protein interactions occurring as new and reactive metal surfaces are generated during wear testing. The development of this analytical methodology will allow new studies to clarify the role of SBL solutions in wear simulation studies and the interactions and lubricating properties of serum proteins with prosthetic surfaces other than MOM. PMID- 20583306 TI - Antibacterial effect of polyethyleneimine nanoparticles incorporated in provisional cements against Streptococcus mutans. AB - BACKGROUND: Frequently provisional restorations require long-term permanence in the oral cavity, thus an antibacterial effect is desirable. We hypothesized that this effect may be achieved by incorporating polyethyleneimine (PEI) nanoparticles into provisional cements. METHODS: The nanoparticles antibacterial effect incorporated at 0.5%, 1%, and 2% w/w into provisional cement, was studied in vitro. The antibacterial effect against Streptococcus mutans and Enterococcus faecalis was tested using direct contact test. The data was analyzed using the ANOVA test, with the Dunnett test for multiple pairwise comparisons. RESULTS: A strong antibacterial effect was evident in all test groups after an aging period of 14 days against S. mutans and E. faecalis (p < 0.05). A significant effect was found between study groups 0.5% w/w and 1% w/w group, as well as between study groups 0.5% w/w and 2% w/w for E. faecalis (p < 0.05). No significant difference was found between study groups 1% w/w and 2% w/w. The growth rate graphs depict an effective bacteria inhibition starting from 1% w/w. CONCLUSION: PEI nanoparticles incorporated at low concentrations in a provisional cement exhibit antibacterial effect against S. mutans and E. faecalis for a period of 14 days. The minimum effective concentration suggested is 1% w/w. CLINICAL IMPLICATIONS: Incorporation of nanoparticles may prevent caries and inflammation, and thereby improve the results of the prosthetic treatment. Further investigation is necessary on the effect on mechanical properties and clinical relevance. PMID- 20583305 TI - Rubber-toughening of dimethacrylate dental composite resin. AB - Dimethacrylate dental composite resins exhibit inherently low toughness. Toughening of these materials may reduce the incidence of marginal and bulk fracture of composite restorations. OBJECTIVE: To determine if dimethacrylate dental restorative materials can be rubber-toughened, and if so, to identify a possible mechanism. METHODS: A filler composed of aggregates of polybutadiene/silica as well as irregularly-shaped silica slabs was produced by mixing silica with polybutadiene in dichloromethane. The dried filler was subsequently ground and sieved to < 25 microm. Polybutadiene/silica ratios were varied from 0:1 (control) to 0.5:1. EDAX analysis verified the composition of the complex filler. Filler was added to a bis-GMA/bis-EMA/TEGDMA resin system and fractured in three-point bend test mode at a crosshead speed of 1 mm/min. In addition, 1 bar was fractured at a crosshead speed of 0.001 mm/min to identify a possible mechanism for toughening. RESULTS: In specimens fractured at 1 mm/min, flexural modulus is increased or maintained and flexural strength and energy to break increase as the amount of polybutadiene in the aggregates increases. Cavitation of high-rubber-containing aggregates is demonstrated. In the one specimen fractured at 0.001 mm/min, a marked increase in size of high-rubber containing aggregates along with severe shear damage in the surrounding matrix is shown, suggesting that cavitation with subsequent absorption of energy during shear yielding is the likely mechanism behind the increase in energy to break in bars fractured at 1 mm/min. SIGNIFICANCE: These results indicate that dimethacrylate dental composite materials can be rubber toughened, which may potentially reduce marginal and bulk fractures of composite restorations, and consequently extend their service lifetime. PMID- 20583307 TI - Corticosteroid-releasing cochlear implant: a novel hybrid of biomaterial and drug delivery system. AB - In this study, drug-eluting cochlear implant (CI) electrodes were prepared, and the amount of drug released was determined. Dexamethasone (DEX) (0.25-2% w/w, the weight percent of the final cured polymer) was used as a bioactive agent to suppress postsurgical inflammations upon mixing with a two-part nonrestricted pourable medical-grade silicone elastomer. Batch reproducibility analysis was performed on three consecutive batches. Drug release experiments were accomplished in normal saline medium, where DEX was analyzed via a validated HPLC method. The drug loading percentage and the device surface area were the most dominant parameters explored to monitor the drug release behavior from CI coatings. Total cumulative amount of DEX released from various loaded samples was in the order of 2 > 1 > 0.5 > 0.35 > 0.25% w/w, but the cumulative percentage of drug released showed a reverse order. The DEX dosages between 0.1 and 1 microg were released from samples of smallest to highest loadings during the initial 24 h, and dosages <1-5 microg were released from similar samples of various loadings at the first patency 2 weeks. The extent of crosslinking was only effective on release profile at lower drug loadings of 0.25% w/w relative to 0.5%. It was also found that release profile was not affected by postcuring. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID- 20583309 TI - Advanced glycation end products-induced apoptosis attenuated by PPARdelta activation and epigallocatechin gallate through NF-kappaB pathway in human embryonic kidney cells and human mesangial cells. AB - BACKGROUND: Diabetic nephropathy has attracted many researchers' attention. Because of the emerging evidence about the effects of advanced glycation end products (AGEs) and receptor of AGE (RAGE) on the progression of diabetic nephropathy, a number of different therapies to inhibit AGE or RAGE are under investigation. The purpose of the present study was to examine whether peroxisome proliferator-activated receptor delta (PPARdelta) agonist (L-165041) or epigallocatechin gallate (EGCG) alters AGE-induced pro-inflammatory gene expression and apoptosis in human embryonic kidney cells (HEK293) and human mesangial cells (HMCs). METHODS: The HEK cells and HMC were separated into the following groups: 100 microg/mL AGE alone for 18 h; AGE treated with 1 microM L 165041 or 10 microM EGCG, and untreated cells. Inflammatory cytokines, nuclear factor-kappaB pathway, RAGE expression, superoxide dismutase and cell apoptosis were determined. RESULTS: AGE significantly increased tumour necrosis factor alpha (TNF-alpha), a major pro-inflammatory cytokine. The mRNA and protein expression of RAGE were up-regulated. These effects were significantly attenuated by pre-treatment with L-165041 or EGCG. AGE-induced nuclear factor-kappaB pathway activation and both cells apoptosis were also inhibited by L-165041 or EGCG. Furthermore, both L-165041 and EGCG increased superoxide dismutase levels in AGE treated HEK cells and HMC. CONCLUSIONS: This study demonstrated that PPARdelta agonist and EGCG decreased the AGE-induced kidney cell inflammation and apoptosis. This study provides important insights into the molecular mechanisms of EGCG and PPARdelta agonist in attenuation of kidney cell inflammation and may serve as a therapeutic modality to treat patients with diabetic nephropathy. PMID- 20583311 TI - Myocardial perfusion scintigraphy in asymptomatic diabetic patients: a critical review. AB - The increasing prevalence of diabetes mellitus and the associated high cardiovascular risk has made the non-invasive identification of silent coronary heart disease in diabetic individuals an important issue. This strategy could identify higher risk asymptomatic patients with diabetes mellitus in whom coronary revascularization may improve the outcome beyond that achieved by currently recommended medical management. Stress myocardial perfusion imaging has been shown to be effective in detecting coronary heart disease and predicting adverse cardiac events in asymptomatic diabetic patients. However, the clinical utility of myocardial perfusion scintigraphy is debated intensively due to the paucity of prospective and outcome based evidence. The controversy stems from several observational studies, epidemiologic data and cost-effectiveness analyses. Thus, although several authors and professional organizations advocate the use of stress imaging for screening higher risk asymptomatic diabetic patients, others are cautious in recommending any kind of stress testing in that population. This review is based on a broad survey of the literature and discusses the potential role of stress myocardial perfusion scintigraphy in screening asymptomatic diabetic subjects for coronary heart disease in the current era and in relation with other non-invasive screening tools. PMID- 20583310 TI - The roles of NADPH-oxidase and nNOS for the increased oxidative stress and the oxygen consumption in the diabetic kidney. AB - BACKGROUND: Sustained hyperglycaemia induces increased renal oxygen consumption resulting in reduced oxygen availability in the diabetic kidney. We investigated the roles of the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the neuronal nitric oxide synthase (nNOS) for the increased oxygen consumption in streptozotocin-diabetic rats. METHODS: Oxygen consumption was measured in isolated proximal tubular cells (PTC) from streptozotocin-induced diabetic rats (n = 7-9 per group) with and without chronic treatment with apocynin, a NADPH oxidase inhibitor, or S-methyl-L-thiocitrulline (SMTC), a selective nNOS inhibitor, or a combination of the two and the results were compared to normoglycaemic controls (n = 10). Oxidative stress was estimated from thiobarbituric acid reactive substances and protein expression measured by Western blot. RESULTS: Proximal tubular cells from untreated diabetic rats had increased oxygen consumption compared to controls (40.6 +/- 7.9 versus 10.9 +/- 2.0 nmol/mg protein/min). All treatments reduced the diabetes-induced increase in oxygen consumption (apocynin 10.5 +/- 1.7, SMTC 19.7 +/- 3.0 and apocynin + SMTC 21.6 +/- 3.6 nmol/mg protein/min). Neither apocynin nor SMTC had any effect on the oxygen consumption in cells pre-incubated with ouabain, an inhibitor of active electrolyte transport. Oxidative stress was elevated in the diabetic kidney and inhibited by all treatments. The increased oxygen consumption by diabetic proximal tubular cells correlated with increased protein expressions of p47(phox) and nNOS and the treatments prevented these increases. CONCLUSIONS: Diabetes induces oxidative stress, which increases oxygen consumption in proximal tubular cells. Inhibition of either NADPH-oxidase or nNOS prevented the increased oxygen consumption. The effect of blocking both these enzymes was less than additive suggesting overlapping pathways which warrant further studies. PMID- 20583312 TI - The mitogenicity of insulin analogues in vitro relative to insulin and IGF-I - Response to Kazda et al. AB - Lispro insulin in a malignant cell line resembled IGF-I more closely than insulin. PMID- 20583315 TI - Contribution of case-mix classification to profiling hospital characteristics and productivity. AB - Case-mix classification has made it possible to analyze acute care delivery case volumes and resources. Data arising from observed differences have a role in planning health policy. Aggregated length of hospital stay (LOS) and total charges (TC) as measures of resource use were calculated from 34 case-mix groups at 469 hospitals (1,721,274 eligible patients). The difference between mean resource use of all hospitals and the mean resource use of each hospital was subdivided into three components: amount of variation attributable to hospital practice behavior (efficiency); amount attributable to hospital case-mix (complexity); and amount attributable to the interaction. Hospital characteristics were teaching status (academic or community), ownership, disease coverage, patients, and hospital volume. Multivariate analysis was employed to determine the impact of hospital characteristics on efficiency. Mean LOS and TC were greater for academic than community hospitals. Academic hospitals were least associated with LOS and TC efficiency. Low disease coverage was a predictor of TC efficiency while low patient volume was a predictor of unnecessarily long hospital stays. There was an inverse correlation between complexity and efficiency for both LOS and TC. Policy makers should acknowledge that differentiation of hospital function needs careful consideration when measuring efficiency. PMID- 20583316 TI - Health care utilization, cost burden and coping strategies by disability status: an analysis of the Viet Nam National Health Survey. AB - There is a need for nationally representative information on the affordability of health care by disability status to assist in the design of equitable health systems in developing countries. Using the Viet Nam National Health Survey (2001 2002), this paper analyses health care utilization, cost burden and coping strategies for people with disabilities versus the population at large. The results clearly show that the disabled population are more prone to hospitalization, and spend more on inpatient stays and pharmaceuticals. Households with disabled members are at greater risk of catastrophic health expenditures and debt financing, posing a serious threat to economic welfare. PMID- 20583317 TI - Skin sensitization, false positives and false negatives: experience with guinea pig assays. AB - The advent of the local lymph node assay (LLNA), and efforts to develop in vitro alternatives for the identification of skin sensitizing chemicals has focused attention on the issue of false positive and false negative results. In essence, the question becomes 'what is the gold standard?' In this context, attention has focused primarily on the LLNA as this is now the preferred assay for skin sensitization testing. However, for many years prior to introduction of the LLNA, the guinea pig maximization test and the occluded patch test of Buehler were the methods of choice. In order to encourage a more informed dialogue about the relative performance, accuracy and applicability of the LLNA and guinea pig tests, we have here considered the extent to which guinea pig methods were themselves subject to false positives and negative results. We describe and discuss here well-characterized examples of instances where both false negatives (including abietic acid and eugenol) or false positives (including vanillin and sulfanilic acid) have been recorded in guinea pig tests. These and other examples are discussed with particular reference to the fabrication of a gold standard dataset that is required for the validation of in vitro alternatives. PMID- 20583318 TI - Comparative study on the influence of subcutaneous administration of diphenyl and dicholesteroyl diselenides on sulphydryl proteins and antioxidant parameters in mice. AB - Although in vitro data from our previous studies show that the antioxidant effect and reactions of both diphenyl diselenide (DPDS) and dicholesteroyl diselenide (DCDS) towards thiol-containing proteins differ considerably, the present study sought to evaluate the interaction of both organodiselenides with thiol containing proteins in vivo. Mice were injected subcutaneously with DPDS or DCDS previously dissolved in soya bean oil at doses of 0.5 mmol kg-1 body weight for four consecutive days. The activities of delta aminolevulinic acid dehydratase (ALA-D), Na+/K+-ATPase, and isoforms of lactate dehydrogenase (LDH) and catalase were investigated. In addition, the antioxidant status of the mice was determined by measuring the levels of glutathione (GSH), vitamin C (Vit C) and thiobarbituric acid reactive substances. The results show that both diselenides significantly increased the levels of GSH and Vit C but did not markedly alter other antioxidant indices. With respect to the thiol-containing enzymes that were evaluated, DPDS and not DCDS caused a marked reduction in the activities of hepatic ALA-D; however, both diselenides inhibited all isoforms of LDH evaluated. In addition, the activities of cerebral Na+/K+-ATPase were not markedly inhibited by both diselenides, suggesting that this cerebral enzyme may not be a molecular target of organodiselenides toxicity. Taken together, the pharmacological and toxicological chemistry of organoselenium compounds is complex and multifactorial and is dependent on delicate equations which include vehicle solution, animal species and mode of delivery. PMID- 20583319 TI - Ion channels in toxicology. AB - Ion channels play essential roles in human physiology and toxicology. Cardiac contraction, neural transmission, temperature sensing, insulin release, regulation of apoptosis, cellular pH and oxidative stress, as well as detection of active compounds from chilli, are some of the processes in which ion channels have an important role. Regulation of ion channels by several chemicals including those found in air, water and soil represents an interesting potential link between environmental pollution and human diseases; for instance, de novo expression of ion channels in response to exposure to carcinogens is being considered as a potential tool for cancer diagnosis and therapy. Non-specific binding of several drugs to ion channels is responsible for a huge number of undesirable side-effects, and testing guidelines for several drugs now require ion channel screening for pharmaceutical safety. Animal toxins targeting human ion channels have serious effects on the population and have also provided a remarkable tool to study the molecular structure and function of ion channels. In this review, we will summarize the participation of ion channels in biological processes extensively used in toxicological studies, including cardiac function, apoptosis and cell proliferation. Major findings on the adverse effects of drugs on ion channels as well as the regulation of these proteins by different chemicals, including some pesticides, are also reviewed. Association of ion channels and toxicology in several biological processes strongly suggests these proteins to be excellent candidates to follow the toxic effects of xenobiotics, and as potential early indicators of life-threatening situations including chronic degenerative diseases. PMID- 20583320 TI - Effects of (+)-catechin and (-)-epicatechin on heterocyclic amines-induced oxidative DNA damage. AB - The aim of the present study was to evaluate the protective effect of (+) catechin and (-)-epicatechin against 2-amino-3,8- dimethylimidazo[4,5 f]quinoxaline (8-MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8 diMeIQx) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP)-induced DNA damage in human hepatoma cells (HepG2). DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. Increasing concentrations of 8-MeIQx, 4,8-diMeIQx and PhIP induced a significant increase in DNA strand breaks and oxidized purines and pyrimidines in a dose-dependent manner. Among those, PhIP (300 um) exerted the highest genotoxicity. (+)-Catechin exerted protection against oxidized purines induced by 8-MeIQx, 4,8-diMeIQx and PhIP. Oxidized pyrimidines and DNA strand breaks induced by PhIP were also prevented by (+)-catechin. Otherwise, (-) epicatechin protected against the oxidized pyrimidines induced by PhIP and the oxidized purines induced by 8-MeIQx and 4,8-diMeIQx. One feasible mechanism by which (+)-catechin and (-)-epicatechin exert their protective effect towards heterocyclic amines-induced oxidative DNA damage may be by modulation of phase I and II enzyme activities. The ethoxyresorufin O-deethylation (CYP1A1) activity was moderately inhibited by (+)-catechin, while little effect was observed by (-) epicatechin. However, (+)-catechin showed the greatest increase in UDP glucuronyltransferase activity. In conclusion, our results clearly indicate that (+)-catechin was more efficient than (-)-epicatechin in preventing DNA damage (strand breaks and oxidized purines/pyrimidines) induced by PhIP than that induced by 8-MeIQx and 4,8-diMeIQx. PMID- 20583321 TI - The cell wall integrity checkpoint: coordination between cell wall synthesis and the cell cycle. AB - The cell wall is an essential cellular component for the survival of fungi. The cell wall of the budding yeast Saccharomyces cerevisiae undergoes remodelling during the cell cycle. Evidence is accumulating that there are regulatory mechanisms that link cell wall remodelling and cell cycle progression. Here, we review one such mechanism, known as the 'cell wall integrity checkpoint', which functions to control cell cycle progression in response to cell wall perturbation. PMID- 20583322 TI - An online method combining a Gasbench II with continuous flow isotope ratio mass spectrometry to determine the content and isotopic compositions of minor amounts of carbonate in silicate rocks. AB - An online method using continuous flow isotope ratio mass spectrometry (CF-IRMS) interfaced with a Gasbench II device was established to analyze carbon and oxygen isotopic compositions and to estimate the content of minor amounts of carbonate in silicate rocks. The mixtures of standard materials and high-purity quartz are firstly used to calibrate different quantities of carbonate in silicates. The results suggest that the accuracy and precision of the online analysis are both better than those obtained using an offline method. There is a positive correlation between the carbonate weight and the Mass44 ion beam intensity (or peak area). When the weight of carbonate in the mixtures is greater than 70 microg (equal to approximately 1800 mV Mass44 ion beam intensity), the delta(13)C and delta(18)O values of samples usually have accuracy and precision of +/-0.1 per thousand and +/-0.2 per thousand (1sigma), respectively. If the weight is less than 70 microg, some limitations (e.g., not perfectly linear) are encountered that significantly reduce the accuracy and precision. The measured delta(18)O values are systematically lower than the true values by -0.3 to -0.7 per thousand; the lower the carbonate content, the lower the measured delta(18)O value. For samples with lower carbonate content, the required phosphoric acid doses are higher and more oxygen isotope exchanges with the water in the phosphoric acid. To guarantee accurate results with high precision, multiple analyses of in-house standards and an artificial MERCK sample with delta(13)C values from -35.58 to 1.61 per thousand and delta(18)O from 6.04 to 18.96 per thousand were analyzed simultaneously with the unknown sample. This enables correction of the measured raw data for the natural sample based on multiple point normalization. The results indicate that the method can be successfully applied to a range of natural rocks. PMID- 20583323 TI - Analysis of triglycerides in food items by desorption electrospray ionization mass spectrometry. AB - The triglyceride composition and oxidation behavior of edible oil and margarine samples were analyzed by desorption electrospray ionization mass spectrometry (DESI-MS). For the characterization of the lipids, the chain length and the degree of unsaturation of the fatty acids were determined. The measurements were carried out in positive ion mode; the triglycerides were detected as alkali metal or ammonium adducts. The DESI solvent was water/methanol 1:1 (v/v); measurements were carried out both with and without the addition, as an ionizing agent, of ammonium acetate that enhances the signal intensity of the ammonium adduct ions. The spectra were interpreted for both cases and intensities were compared. Triglyceride monomers and dimers were observed in the spectra. Tandem mass spectrometric (MS/MS) measurements were carried out to determine the structure of the triglycerides. It was demonstrated that the terminal fatty acids in the sn1- or sn3-position are more likely to be cleaved than the internal fatty acid (sn2 position). Characteristic triglyceride patterns were obtained using a simple and rapid sample preparation protocol comprising the simple deposition of samples onto a glass carrier surface. The triglyceride data was analyzed by principal component analysis (PCA). The different edible oils were clearly separated and the hydrogenated derivatives were identified by their triglyceride spectra. The oxidation of the oil samples was observed and the oxidation products were detected and identified. This method provides a fast and simple technique for the detection and analysis of triglycerides in oil- or fat-containing samples ranging from food items to tissue samples. The potential application areas include nutritional studies, the food industry and cosmetics. PMID- 20583324 TI - Structural characterization of poly(amino)ester dendrimers and related impurities by electrospray tandem mass spectrometry. AB - An acid-terminated poly(amino)ester dendrimer was studied by electrospray ionization tandem mass spectrometry to establish its fragmentation pathways, with the aim of using them to investigate the structure of any defective molecules generated during the dendrimer synthesis. This poly(amino)ester dendrimer could be ionized in both polarities but the most structurally relevant dissociation pathways were found from the deprotonated molecule in negative ion mode. The dissociation pattern of this dendrimer is fully described and supported by accurate mass measurements. The main dissociation reactions of the negatively charged polyacidic dendrimer were shown to consist of (i) the release of carbon dioxide and ethene within a branch, which proceeds as many times as intact neutral branches are available; and (ii) the elimination of an entire dendrimer arm. Monitoring the occurrence of these reactions together with any deviation from these two main routes allowed six major dendritic impurities to be structurally characterized. PMID- 20583325 TI - Use of stable isotope labeled probes to facilitate liquid chromatography/mass spectrometry based high-throughput screening of time-dependent CYP inhibitors. AB - Inhibition curve shift is a commonly used approach for screening of time dependent CYP inhibitors which requires parallel paired incubations to obtain two inhibition curves for comparison. For the control incubation, a test compound is co-incubated with a probe substrate in human liver microsomes (HLM) fortified with NADPH; for the time-dependent incubation (TDI), the test compound is pre incubated with NADPH-fortified HLM followed by a secondary incubation with a probe substrate. For both incubations, enzyme activity is measured respectively by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis of the CYP specific metabolite, and a TDI inhibitor can be readily identified by inhibition curve shifting as a result of CYP inactivation by the test compound during the pre-incubation. In the present study, we describe an alternative approach to facilitate TDI screening in which stable isotope labeled CYP-specific probes are used for the TDI, and non-labeled substrates are included in the control incubation. Because CYP-specific metabolites produced in the TDI are stable isotope labeled, two sets of incubation samples can be combined and then simultaneously analyzed by LC/MS/MS in the same batch run to reduce the run time. This new method has been extensively validated using both a number of known competitive and TDI inhibitors specific to five most common CYPs such as 1A2, 2C9, 2C19, 2D6, and 3A4. The assay is performed in a 96-well format and can be fully automated. Compared to the traditional method, this approach in combination with sample pooling and a short LC/MS/MS gradient significantly enhances the throughput of TDI screening and thus can be easily implemented in drug discovery to evaluate a large number of compounds without adding additional resource. PMID- 20583326 TI - New features on the fragmentation patterns of homoisoflavonoids in Ophiopogon japonicus by high-performance liquid chromatography/diode-array detection/electrospray ionization with multi-stage tandem mass spectrometry. AB - Homoisoflavonoids, a special class of flavonoids, are mainly distributed in the Liliaceae family and have various biological activities. Previously, very little research has been reported on the gas-phase fragmentation patterns of homoisoflavonoids by electrospray ionization mass spectrometry. In this paper, we report the use of high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) to study the fragmentation behavior of 11 homoisoflavonoid standards and to analyze homoisoflavonoids in Ophiopogon japonicus. In total, 28 homoisoflavonoids (including seven novel constituents) were characterized. The deprotonated [M--H](-) molecules of the homoisoflavonoids containing a saturated C2--C3 bond afforded the A or B product ion (base peak) according to whether the B-ring was substituted with a hydroxyl group. For the homoisoflavonoids containing a C-2-C-3 double bond, the product ions (A or C ion) were created from the precursor [M-H](-) ion as the base peak when the B-ring was substituted with a hydroxyl group. The homoisoflavonoids carrying a formyl group in the A-ring readily eliminated one molecule of CO to form the product ion [M + H-CO](-) (base peak) irrespective whether the C-2-C-3 bond was saturated or not. This product ion afforded the [M-H-CO-B-ring--CH(2) + H](-) ion by cleavage of the C3-C9 bond. This latter product ion always appeared in tandem mass (MS/MS) spectra of type I homoisoflavonoids. The common features of flavonoids observed during the gas-phase fragmentation mechanisms were the loss of the following groups: 15 Da (CH(3)), 18 Da (H(2)O), 28 Da (CO), 44 Da (CO(2)) and 46 Da (CH(2)O(2)). A retro-Diels-Alder (RDA)-like cleavage was also observed for the homoisoflavonoids. The different gas-phase fragmentation routes were characterized for the deprotonated molecules obtained from the various homoisoflavonoids and collision-induced dissociation (CID) fragmentation differences were noted for the different locations of the various substituents. In conclusion, we can say that this study allowed us to structurally elucidate and identify homoisoflavonoids distributed in related plants and their complex prescriptions. PMID- 20583327 TI - Treatment of fetal goitrous hypothyroidism: value of direct intramuscular L thyroxine therapy. PMID- 20583329 TI - A new look at stress disorder. PMID- 20583328 TI - Bladder control. Treatment can help. PMID- 20583330 TI - Aging without getting old. Vitality for life. PMID- 20583331 TI - I have heart surgery scheduled and it has given me a wake-up call to stop smoking. However, I've heard that stopping before surgery might cause more harm than good. Is this true? PMID- 20583332 TI - Control your blood sugar with a supplement? PMID- 20583333 TI - Theoretical predictions of wurtzite III-nitride nano-materials properties. AB - In this paper, top-down and bottom-up approaches are used to predict material properties of group III-nitride nanostructures. The first approach calculates the melting temperature, melting enthalpy, Debye temperature and energy bandgap of InN, GaN and AlN through classical thermodynamics. The second approach calculates the surface energies in the liquid and solid states of the considered nitrides materials through molecular dynamics. Moreover, the liquid and solid surface energies of the zinc-blende and wurtzite III-V materials are compared. Finally, the phase diagram of a ternary III-nitride nanomaterial, AlGaN, is presented and the variation of its energy bandgap with composition is predicted. PMID- 20583334 TI - In vivo kinetic degradation analysis and biocompatibility of aliphatic polyester polyurethanes. AB - Polyester polyurethanes incorporating polyhedral oligosilsesquioxane (POSS) as the crystalline hard block were evaluated for biocompatibility and degradation over 24 weeks in vivo. In vitro studies were also used to predict the onset of mass loss. The molecular weight of each sample was found to decrease quickly over an 8 week period and then became constant due to the nondegrading POSS hard block. Kinetic analysis of the initial molecular weight change indicated that the degradation rate was dependent on the soft block composition. Crystallinity, melting temperature, and heat of fusion of the polyurethanes were found to increase during degradation as the amorphous polyester soft segments were hydrolyzed. The histological analysis of each polymer demonstrated rapid resolution of the acute and chronic inflammatory responses and the development of expected, normal foreign body reaction, consisting of adherent macrophages and foreign body giant cells on the surface of the polymers, and fibrous capsule formation around the polymer. No acute and/or chronic inflammation was seen after 3 weeks, indicating that the polymers in film form and biodegraded form, that is, particles, were biocompatible and did not elicit inflammatory responses expected for toxic or nonbiocompatible materials. PMID- 20583335 TI - Healthcare-associated infections studies project: an American Journal of Infection Control and National Healthcare Safety Network data quality collaboration. PMID- 20583336 TI - Recent advances in the rapidly evolving field of fibroblast growth factor 23 in chronic kidney disease. AB - PURPOSE OF REVIEW: In recent years, there has been an increasing awareness of the central regulatory role of fibroblast growth factor 23 (FGF23) in mineral metabolism and its particular prominence in patients with chronic kidney disease (CKD). RECENT FINDINGS: FGF23 is a powerful predictor of adverse clinical outcomes in CKD that appears to be superior to existing mineral metabolism markers such as serum phosphate and parathyroid hormone. Interesting new data suggest a central role of bone health in the regulation of FGF23 secretion, whereas another important new study reported that virtually all circulating FGF23 in advanced renal failure is biologically intact. Finally, new data demonstrate the ability to alter FGF23 levels using common CKD therapies such as phosphate binders, active vitamin D, and cinacalcet. SUMMARY: Although FGF23 was originally discovered in studies of rare diseases, we expect that its primary utility in mainstream clinical practice will ultimately lie in the management of CKD. Emerging data highlight the potential of FGF23 as a novel diagnostic to identify CKD patients at the highest risk for disease progression, cardiovascular disease, and death, and those who might benefit from early phosphorus-related therapies before the onset of overt hyperphosphatemia. PMID- 20583337 TI - Rational design of bridging selenocyanates by thermal decomposition reactions. AB - The powerful use of thermal decomposition reactions as tool for the directed synthesis of a new selenocyanate is described. This method offers a facile access to a large number of new compounds, in which the metal centers are bridged by small anionic linker ligands and therefore, cooperative magnetic phenomena can be expected. PMID- 20583338 TI - Obesity: Light-to-moderate alcohol consumption may reduce weight gain in middle aged or older women. PMID- 20583339 TI - Diabetes: Progression of diabetic retinopathy found to be a potential risk during pregnancy. PMID- 20583340 TI - Lipids: Eprotirome shows promise as a novel way to target dyslipidemia. PMID- 20583341 TI - Diagnosis: Neonatal growth hormone deficiency. PMID- 20583342 TI - Cancer: Second-line therapy for adrenocortical carcinoma proves beneficial. PMID- 20583343 TI - Cancer: Long-term use of metformin could protect against breast cancer. PMID- 20583344 TI - Use of cerebral oximetry for monitoring cardiac output during off-pump implantation of Jarvik 2000 left ventricular assist device. PMID- 20583345 TI - Management of rising prostate-specific antigen following a negative biopsy. PMID- 20583346 TI - Use of metal prosthesis and risk of bone cancer. PMID- 20583347 TI - Polymer stabilized cholesteric liquid crystal arrays for detecting vaporous amines. AB - In this paper, we report the utility of a colorimetric polymer stabilized cholesteric liquid crystal (PSCLC) array for detecting vaporous amines. The PSCLC with various polymer concentrations (5-20% w/w) is made into an array which shows distinct color changes upon exposure to 400 parts-permillion (ppm) octylamine vapor at 23-35 degrees C. Interestingly, PSCLC shows stronger response to primary amine over secondary amine, tertiary amine, ester, aldehyde, and alkane having similar molecular weights. PSCLCs also give detection limits as low as 2 ppmv for decylamine. Because PSCLC is transparent at room temperature and changes color upon exposure to amine vapors, it can be coated on windows or safety goggles to offer protection against amine vapors. PMID- 20583348 TI - By the way, doctor. I wash my face very little because I have heard soaps, no matter how mild, dry out skin. What do you think--what should I wash my face with? PMID- 20583349 TI - By the way, doctor. In addition to a multivitamin, I have been taking vitamin B12 supplements (1,000 mcg) for a few years, hoping to increase my energy. My recent blood profile showed a high level of B12(1,826 pg/ml). Should I stop taking B12? My energy is about the same. PMID- 20583350 TI - By the way, doctor. I'm starting to check my blood pressure at home. When during the day should I do it? PMID- 20583351 TI - Persistence pays off in cardiac rehabilitation. At home or away, a rehab program can do wonders for your heart. PMID- 20583352 TI - Better ways to get your produce. Farmers' markets and growing your own trump the grocery store. PMID- 20583353 TI - Coronary artery vasospasm. A sudden spasm of the coronary arteries can feel like a heart attack. PMID- 20583354 TI - Clearing clogged arteries in the neck. Balloon angioplasty is getting better at unblocking carotid arteries, but surgery still has the edge. PMID- 20583355 TI - Ask the doctor. I am 86 years old and have high blood pressure and diabetes. As part of my last physical exam, my doctor ordered tests to check my carotid arteries. They showed that one was nearly 70% blocked. My doctor said I had to have surgery right away of I would have a stroke. Is she right? I am the only person taking care of my 88-year-old husband, and can't be away from him for long. PMID- 20583356 TI - Your choice for dieting. PMID- 20583357 TI - Ask the doctor. Last year I had a deep-vein thrombosis with a small pulmonary embolism, apparently precipitated by flying across the country without getting up and walking around. I did just fine with anticoagulation and am now off all medications. Is it safe to fly again? If so, what precautions would you recommend? PMID- 20583358 TI - Ask the doctor. I have been taking CholestOff for a few years to lower my cholesterol. Does CholestOff have any long-term side effects that might be a problem for breast cancer survivors like me? PMID- 20583359 TI - By the way, doctor. If coffee constricts blood vessels, why would it help migraine sufferers, since the constriction curtails blood flow, which would seem to cause more pain? PMID- 20583360 TI - By the way, doctor. Thiazide diuretics are often recommended as the first medication to use to control blood pressure, but I've heard that a large study called ALLHAT found an association between thiazide diuretics and diabetes. Is this something to be concerned about? PMID- 20583361 TI - By the way, doctor. My 78-year-old husband has wet macular degeneration. He is being treated with a drug called Avastin. Is that a good choice? PMID- 20583362 TI - By the way, doctor. I belch a lot and get a feeling of fullness in the upper abdomen. Is this common condition? What are the causes and cures? I would prefer natural remedies. PMID- 20583363 TI - By the way, doctor. I'm in good health and have a good lipid profile but occasionally have a yearning for brisket or corned beef. I recently read that even one meal heavy in fat could cause atherosclerosis. What do you think? PMID- 20583364 TI - Gender and the categories of experienced history. PMID- 20583365 TI - Writing gender into history and history in gender: "Creating a Nation" and Australian historiography. PMID- 20583366 TI - Dealing with love: the ambiguous independence of the single woman in early modern England. PMID- 20583367 TI - Pictures from the margins of marriage: representations of spinsters and single mothers in the mid-Victorian novel, inter-war Hollywood melodrama and British film of the 1950s and 1960s. PMID- 20583368 TI - Masters of the earth: gender and destalinisation in Soviet reformist painting of the Khrushchev thaw. PMID- 20583369 TI - Rethinking gender and power in the US occupation of Japan, 1945-1952. PMID- 20583370 TI - Savage irony: the imaginative power of the "military comfort women" in the 1990s. PMID- 20583371 TI - Gender, slavery and the making of new world identities. PMID- 20583372 TI - Women's history and biography. PMID- 20583373 TI - Periodontal treatment could improve glycaemic control in diabetic patients. Evidence-based Dentistry 2009; 10: 20-21. PMID- 20583375 TI - Vitamin D: a bright spot in nutrition research. Too little of the sunshine vitamin linked to heart disease, statin-related muscle pain, other conditions. PMID- 20583374 TI - Of sheep and scribbling: women and writing in (mostly) early modern England. PMID- 20583377 TI - Blood pressure: how low should you go? Too low may be a problem for people with clogged coronary arteries. PMID- 20583378 TI - Peripheral artery disease and stroke. PMID- 20583379 TI - Ask the doctor. I've heard you should take an aspirin if you think you are having a heart attack. I already take aspirin (325 mg) every day. Should I still take an aspirin if I feel a heart attack coming on? PMID- 20583380 TI - Ask the doctor. What is the story on using red yeast rice to lower cholesterol? You have warned readers against using it in the past, but I heard about a new study that shows it works. Are you ready to admit you are wrong on this one? PMID- 20583381 TI - Genetics and dentistry. PMID- 20583383 TI - Retraction of an original article in whole. Fournier's gangrene and its management at a tertiary care hospital. PMID- 20583382 TI - Searchers of the dead: authority, marginality, and the interpretation of plague in England, 1574-1665. PMID- 20583384 TI - Monitoring the coverage and impact of human papillomavirus vaccine - report of WHO meeting, November 2009. PMID- 20583385 TI - Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2010 (data received in WHO headquarters as of June 1 2010). PMID- 20583386 TI - Monthly report on dracunculiasis cases, January-April 2010. PMID- 20583387 TI - Progress in leprosy control:Indonesia, 1991-2008. PMID- 20583388 TI - Superior results following the Ross procedure in patients with congenital heart disease. AB - BACKGROUND AND AIM OF THE STUDY: The Ross procedure is a versatile operation that can be applied for aortic valve replacement (AVR) in patients with congenital heart disease (CHD), including small infants and those with complex left ventricular outflow tract (LVOT) obstruction. Herein, the clinical outcome is reported following the Ross procedure in patients with CHD at the authors' institution. METHODS: The medical records of patients who underwent the Ross procedure for CHD between 1991 and 2007 were reviewed. A competing-risks methodology was used to determine the time-related prevalence and associated factors for three mutually exclusive end states after the Ross procedure, namely death prior to subsequent cardiac reoperation, cardiac reoperation, and survival without subsequent reoperation. RESULTS: A total of 151 patients (98 males, 53 females) was identified. The median age at the time of surgery was 8.6 years (range: 4 days to 33 years). Previously, 103 patients (68%) had undergone cardiac interventions, and 43 (28%) required LVOT enlargement (modified Ross-Konno procedure). A competing-risk analysis showed that, at 10 years after the Ross procedure, 8% of patients had died without subsequent reoperation, 26% underwent cardiac reoperation, and 66% remained alive without further reoperation. The 10 year freedom from autograft and homograft reoperation was 95% and 71%, respectively. Factors associated with early risk of mortality were age < 1 year and no prior surgical/percutaneous intervention at the time of the Ross procedure. Surgical factors associated with cardiac reoperation were concurrent cardiac surgery and the use of fresh homografts. There were no bleeding or thromboembolic complications, and the 15-year freedom from endocarditis was 95%. Ultimately, 99% of the survivors were in NYHA class I or II. CONCLUSION: The Ross procedure remains the authors' procedure of choice for AVR in patients with CHD. Outcomes in infants aged < 1 year may improve with better patient selection and palliative surgical/percutaneous interventions prior to valve replacement. The late survival was excellent and valve-related complications were minimal. The high autograft longevity led to few patients requiring late reoperation for graft replacement. PMID- 20583389 TI - Clinical experience with expanded use of the Ross procedure: a paradigm shift? AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the short-term survival and functional outcome after the Ross procedure, with expanded inclusion criteria. METHODS: A total of 91 patients (21 females, 70 males; mean age 57.3 +/ 13.1 years; range: 0.1-74 years) underwent aortic valve replacement (AVR) with a Ross procedure at the authors' institution during the year 2007. The underlying valve diseases were stenosis in 60 patients, regurgitation in 17, and a mixed lesion in 14. Seven patients suffered from acute infective endocarditis, and in five patients the Ross operation was a reoperative procedure. Forty-four patients (48%) underwent surgery in association with concomitant procedures, which included predominantly coronary artery bypass surgery, mitral valve repair or replacement, or procedures of the ascending aorta. RESULTS: The mean cardiopulmonary bypass and aortic cross-clamp times were 147 +/- 31 min (range: 87-246 min) and 124 +/- 26 min (range: 73-195 min), respectively. Hospital mortality was 2.2%. No patient died during the follow up period. The aortic gradient was decreased from 5.1 +/- 2 mmHg at discharge, to 3.2 +/- 1 mmHg during follow up (p < 0.05); at the same times, the mean gradient of the decellularized tissue-engineered pulmonary valve was 2.8 +/- 1 mmHg and 2.7 +/- 1 mmHg, respectively. An echocardiographic examination of neo-aortic valve competence at 12 months revealed no or trivial aortic valve regurgitation in 80 patients, and mild (grade 1+) regurgitation in nine patients. No patient required reoperation of the autograft during follow up. Two patients underwent reconstruction of the right ventricular outflow tract. At 12 months' follow up, all patients enjoyed normal social interactions, were in NYHA functional class I or II, and free from complications. CONCLUSION: The Ross procedure can be offered as an alternative to standard prosthetic AVR with an excellent short-term outcome. The former inclusion/exclusion criteria for this procedure should be re-evaluated. PMID- 20583390 TI - The first fifty consecutive Bentall operations with a prefabricated tissue-valved aortic conduit: a single-center experience. AB - BACKGROUND AND AIM OF THE STUDY: Composite replacement is the standard treatment for the repair of aortic aneurysm with aortic valve pathology. With improved long term durability and no requirement for long-term anticoagulation, tissue-valved conduits have become increasingly popular. Herein are reported the results achieved with 50 consecutive 'Bentall' operations, using the first commercially available prefabricated stentless tissue-valved conduit (Vascutek BioValsalva). METHODS: Between September 2007 and September 2009, a total of 50 patients (10 females, 40 males; mean age 65 +/- 7 years) received a BioValsalva conduit. Concomitant procedures included coronary artery bypass grafting (CABG; n = 15), other valve (n = 5), and aortic arch replacement with circulatory arrest (n = 20; three of these had an additional frozen elephant trunk). Four of the procedures were re-operations. A six-month follow up with echocardiography and clinical examination was completed in 25 patients. RESULTS: The 30-day mortality was 8% (4/50). Three of these patients underwent concomitant procedures. The cardiopulmonary bypass (CPB) and cross-clamp times were 178 +/- 30 min and 106 +/ 7 min, respectively. The triple-layered vascular graft proved to be hemostatic, without suture-line bleeding. Both, the initial and follow up echocardiography showed no valvular insufficiency, with a mean gradient of 13 +/- 5 mmHg. All patients were in NYHA class I-II. CONCLUSION: The BioValsalva prefabricated tissue-valved conduit showed very good early results. The ischemic time required to construct a 'home-made' stentless tissue-valved conduit was eliminated, thus reducing the cross-clamp time. The conduit also offered the hemodynamic advantages of a stentless valve. PMID- 20583391 TI - In-vivo blood velocity and velocity gradient profiles downstream of stented and stentless aortic heart valves. AB - BACKGROUND AND AIM OF THE STUDY: Abnormal flow conditions across aortic bioprosthetic valves may result in degenerative processes. Thus, it is important to implant biological valve prostheses with velocity profiles similar to those of native valves. The study aim was to compare blood velocity and velocity gradient profiles downstream of stented and stentless aortic valves implanted in pigs, and in native porcine valves. METHODS: Stented valve prostheses (Mitroflow, n = 7) or stentless valve prostheses (Solo, n = 5 or Toronto SPV, n = 7) were implanted into pigs; the native valve was retained in eight animals. After weaning the animals from cardiopulmonary bypass, cardiac magnetic resonance imaging was performed to determine the blood velocities and velocity gradient profiles. RESULTS: The native valves had a significantly lower peak velocity (92 +/- 26 cm/s) than the artificial valves (Solo: 247 +/- 107 cm/s; Toronto: 252 +/- 41 cm/s; Mitroflow: 229 +/- 18 cm/s). The native valves exhibited a flat velocity profile during systole, whereas the Solo valve, and especially the Toronto SPV valve, displayed more parabola-shaped velocity profiles; velocity profiles downstream of the Mitroflow valve exhibited a flat shape. The native valves had a lower mean velocity gradient at peak systole (p < 0.0001). The velocity gradient percentage above mean was lowest for the native valve (0.14 +/- 0.11; p < 0.0001), while the Mitroflow valve had a percentage of 0.57 +/- 0.09, which was lower than the Solo valve (0.69 +/- 0.12; p = 0.074), and significantly lower than the Toronto valve (0.70 +/- 0.08; p = 0.015). All valves displayed high velocity gradients adjacent to the aortic wall; in particular, the Toronto SPV which also had high velocity gradients at the center of the vessel. CONCLUSION: All of the artificial valves tested had a significantly higher mean velocity gradient and peak velocity than the native valves. However, the Mitroflow had a mean velocity and a velocity gradient percentage lower than the two stentless valves. The Solo and Mitroflow valves displayed velocity profiles most like native valves, while the Toronto valve had a more irregular asymmetric velocity profile. PMID- 20583392 TI - Mitral valve replacement with the Quattro stentless pericardial bioprosthesis: mid-term clinical and echocardiographic follow up. AB - BACKGROUND AND AIM OF THE STUDY: Preservation of the subvalvar apparatus during mitral valve replacement (MVR) is associated with improved ventricular function and patient outcome. The Quattro valve is a chordally supported stentless mitral valve bioprosthesis that undergoes anticalcification treatment and is sutured to both annulus and papillary muscles heads, thus preserving annuloventricular continuity. The study aim was to assess the mid-term hemodynamic and functional results following MVR using the Quattro valve. METHODS: Between 1998 and 2005, a total of 76 patients received the Quattro valve at the authors' institution. A competing-risks methodology was used to determine the time-related prevalence of four mutually exclusive end-states: death; subsequent valve removal for dysfunction; subsequent valve removal for endocarditis; and survival without valve reoperation. Serial echocardiograms (n = 321) were collected, and regression models adjusted for repeated measures were used to model the longitudinal progression of the prosthesis mitral valve area (MVA), peak gradient (PG), mean gradient (MG), mitral regurgitation (MR) and ejection fraction (EF) over time. RESULTS: The median patient age was 33 years, and the most common underlying pathology rheumatic fever (46%). Of the patients, 35 (46%) had undergone a prior mitral surgery. A competing-risks analysis showed that, at 10 years after Quattro implantation, 11% of patients had died without subsequent replacement, 57% underwent valve replacement for dysfunction, 7% for endocarditis, and 26% remained alive without reoperation. Overall, 24 valves were explanted (five for endocarditis and 19 for valve malfunction). On multivariable analysis, risk factors for reoperation were prior mitral surgery (p = 0.03), especially prior MVR (p = 0.04). Serial echocardiographic data showed progressive increases in PG and MR, a decrease in MVA, and stable MG and EF. CONCLUSION: In a fairly young population, the longevity of the Quattro valve was limited by a high risk of endocarditis and reoperation requirement. In addition to valve degeneration, malfunction without structural change was a frequent cause of prosthesis replacement. This may be due to an unpredictable geometric ventricular adaptation to the prosthesis, with subsequent development of prosthesis insufficiency or subvalvar stenosis. Further evaluation is required to identify the best candidates to receive the Quattro bioprosthesis. PMID- 20583393 TI - Infective endocarditis in patients with diabetes mellitus. AB - BACKGROUND AND AIM OF THE STUDY: Numerous studies have been conducted to investigate the conditions associated with poor outcome among patients with infective endocarditis (IE). Yet, diabetes mellitus alone has rarely been analyzed as participating in the prognosis, and few data are available relating to the clinical characteristics of IE in diabetics. The study aim was to assess the influence of diabetes mellitus on the characteristics and prognosis of IE, and to identify predictors of poor outcome among diabetic patients with this condition. METHODS: The study included consecutive patients with IE who had presented to a tertiary center between 1990 and 2006. All patients underwent transthoracic and transesophageal echocardiography. Three or more blood cultures were collected from each patient. Records of all patients were collected prospectively into a computerized database. RESULTS: Among 309 patients with definitive IE (according to modified Duke criteria), 38 (12%) had diabetes mellitus. Typically, diabetic patients were older than non-diabetics (67.1 +/- 10.4 versus 60.7 +/- 15.8 years; p < 0.001), had more serious comorbidities (Charlson index 2.8 +/- 0.7 versus 1.2 +/- 0.5; p = 0.005), and a higher frequency of enterococcal endocarditis. No differences were noted between patients with or without diabetes mellitus for the valve involved, nor for the subvalvular involvement. In a multivariate analysis, diabetes mellitus was identified as an independent predictor of mortality (OR 2.49; 95% CI 1.15-5.62). Surgery was performed in the active phase in 139 patients: surgical mortality was higher for diabetic patients (29% versus 10% p = 0.049). In-hospital mortality was significantly higher among diabetic patients (34%) than in non-diabetics (20%) (p = 0.002). Enterococcal endocarditis, left ventricular ejection fraction < 0.45, multi-organ failure, heart failure, persistent fever after one week of antibiotic therapy, and a Charlson index > 3 were associated with an increased mortality among diabetic patients. CONCLUSION: Diabetes mellitus represents a relevant risk factor for a worse clinical course and outcome of IE. PMID- 20583394 TI - Considerations in timing of surgical intervention for infective endocarditis with cerebrovascular complications. AB - BACKGROUND AND AIM OF THE STUDY: The timing of the surgical intervention for active infective endocarditis (IE) is particularly difficult when there is a cerebrovascular complication. The study aim was to investigate the results of surgical treatment for active IE in patients with recent cerebrovascular events, and to evaluate the relationship between the size of cerebral infarction and timing of the surgical intervention. METHODS: Between January 1991 and April 2009, the details of 21 patients with cerebrovascular complications before surgery were analyzed retrospectively. Types of complication included cerebral infarction (n = 13), hemorrhagic infarction (n = 4), and cerebral hemorrhage (n = 4). The surgical treatment was single valve surgery (n = 14), multiple valve surgery (n = 3), and modified Bentall surgery (n = 4). The mean interval between onset of the cerebrovascular event and surgical intervention was 27.0 +/- 18.8 days. RESULTS: Eight patients underwent surgery within two weeks; among these patient, seven had a small cerebral infarction (< or = 15 mm diameter) and one patient had a cerebral hemorrhage. Postoperative exacerbation of cerebral complications was not observed among the eight patients treated within two weeks. The interval between onset of the cerebral event and cardiac surgery was significantly shorter in patients with a small infarction (18 days) than with a large infarction (38 days) (p < 0.05). None of the patients with a small infarction had postoperative exacerbation of their cerebral complication, even with a significantly shorter interval. However, postoperative hemorrhage into the infarction area was observed in one patient with a large infarction. CONCLUSION: The study results showed that IE patients with a small non-hemorrhagic cerebral infarction may safely undergo cardiac surgery, even within two weeks of the onset of a cerebrovascular event. PMID- 20583395 TI - Short-term results of repeat valve replacement: a predictive factor analysis. AB - BACKGROUND AND AIM OF THE STUDY: The new-generation bioprostheses are associated with a longer lifespan, and therefore tend to be implanted in younger patients. However, with the increase in life expectancy, the trend is towards a higher rate of repeat valve replacement. Hence, the study aim was to evaluate the present mortality and risk factors for repeat valvular surgery. METHODS: A total of 183 consecutive patients (87 males, 96 females; mean age 62 years; range: 28-88 years) who underwent repeat valve replacement at the authors' institution between 2001 and 2004 was reviewed. Reoperations in these patients were required due to structural degeneration of the bioprosthesis (50%), to paravalvular leak (20%), and to prosthetic endocarditis (14%), valve thrombosis (9%), and plasty failure (9%). In total, 105 patients (57%) had received at least one bioprosthesis during the previous operation, 58 (31%) had a mechanical valve, 15 (8%) had an isolated mitral plasty, and five (2%) hybrid procedures. All preoperative and operative risk factors were studied. RESULTS: The overall operative mortality rate was 6.6% (n = 12), but only 3.9% (n = 4) for the bioprosthesis reoperation. The risk factors for mortality included pulmonary hypertension (> 60 mmHg; p = 0.03), renal insufficiency (p = 0.02), more than one repeat valve replacement (p = 0.004), previous mechanical prosthesis (p = 0.02), previous mitral surgery (p = 0.019), and associated tricuspid surgery (p = 0.03). CONCLUSION: The data acquired tended to show that repeat valve replacement of bioprostheses may be carried out with an acceptable operative risk, in connection with the majority of operations on bioprostheses being secondary to structural degeneration of the implant. Hence, in most cases a well-controlled, programmed operation would lead to very low mortality (< 4%), despite a significant morbidity rate. PMID- 20583396 TI - Sildenafil and beraprost combination therapy in patients with pulmonary hypertension undergoing valvular heart surgery. AB - BACKGROUND AND AIM OF THE STUDY: Sildenafil and beraprost, as orally available pulmonary vasodilators, are used increasingly to treat pulmonary hypertension (PH). An evaluation was made, in patients with PH undergoing valvular heart surgery, as to whether preoperative combined oral sildenafil and beraprost treatment could induce synergistic and prolonged pulmonary vasodilation, or result in a loss of pulmonary selectivity. METHODS: Fifty patients scheduled for valvular heart surgery with a mean pulmonary arterial pressure (PAP) > 30 mmHg were randomly assigned to receive either 50 mg oral sildenafil + 40 microg beraprost, or a placebo, 15 min before the induction of anesthesia. Hemodynamic variables were measured intraoperatively. RESULTS: The treatment group had a significantly lower systemic vascular resistance index at 60 min after medication. No other significant intergroup differences in hemodynamic variables were observed. In addition, significantly more patients in the treatment group required vasopressor therapy. In both groups, the PAP was significantly reduced by general anesthesia, and almost normalized after valvular heart surgery. CONCLUSION: Preoperative oral sildenafil and beraprost treatment resulted in a loss of pulmonary selectivity, and did not provide any additional pulmonary vasodilation or favorable perioperative hemodynamics in patients with PH undergoing valvular heart surgery. PMID- 20583397 TI - Simultaneous aortic and mitral valve replacement in children: time-related outcomes and risk factors. AB - BACKGROUND AND AIM OF THE STUDY: Valve replacement in children is problematic, and associated with high anticoagulation-related complications and increased reoperation requirements. Multiple valve replacement may further increase morbidity and worsen outcome. The results are reported of combined aortic valve replacement (AVR) and mitral valve replacement (MVR) in children. METHODS: The medical records of children who underwent simultaneous AVR and MVR between 1984 and 2004 were reviewed, and the short-term and long-term results and variables affecting outcomes explored. The mean duration of follow up was 9.7 +/- 6.6 years. RESULTS: A total of 84 patients (62 males, 22 females; mean age 15.0 +/- 2.2 years) was identified. The underlying pathology was mainly rheumatic (94%) and endocarditis (4%). Among the patients, 21 (25%) had undergone a prior cardiac surgery. The implanted valves were either mechanical (n = 71) or bioprosthetic (n = 13). The average aortic and mitral valve sizes were 22 mm and 29 mm, respectively. In total, 21 patients had concomitant cardiac surgery, most commonly tricuspid valve repair (n = 18). The mean cardiopulmonary bypass time and ischemic time were 142 +/- 47 min and 107 +/- 33 min, respectively. Survival at 30 days and at one year was 96% and 94%, respectively. The overall 15-year survival was 78% (bioprosthesis 92% versus mechanical 76%; p = 0.4). The 15-year freedom from cardiac reoperation was 59%, and 68% and 75% for mitral and aortic reoperation, respectively. Significant risk factors for reoperation were the use of a bioprosthetic valve (p = 0.003) and female gender (p = 0.03). Freedom rates from endocarditis, thromboembolic and bleeding complications at 15 years were 90%, 92%, and 96%, respectively. Among survivors, 95% were in NYHA class I/II. CONCLUSION: Children with rheumatic fever and endocarditis may require simultaneous AVR and MVR. Although the operative mortality is acceptable, patients continue to have constant attrition with time, especially those who have received mechanical prostheses. The risk of cardiac reoperation requirement is high in all patients. Despite the greater need for reoperation, bioprosthetic valves could be offered to selected patients, such as females and those who are non-compliant with anticoagulation regimens. PMID- 20583398 TI - Aortic dilatation in patients with prosthetic aortic valve: comparison of MRI and echocardiography. AB - BACKGROUND AND AIM OF THE STUDY: Patients with prosthetic aortic valve have an increased risk for aortic dissection, which rises further with growing aortic diameters. Thus, accurate aortic monitoring is required. As transthoracic echocardiography (TTE), the current clinical standard, is frequently restricted to the proximal ascending aorta, the use of two-dimensional cardiovascular magnetic resonance (2D-CMR) in transverse orientation was investigated as a screening tool to assess ascending aortic dimensions. METHODS: Fast, non-contrast enhanced, non-breath-hold, steady-state free-precession (SSFP) sequences (1.5 Tesla, slice thickness 7 mm, gap 1.8 mm, scan time 10-15 s) were applied to image the thorax in transverse planes. To test the accuracy of aortic dimensions obtained in this way, comparison was made to contrast-enhanced three-dimensional MR angiography (3D-MRA) as the 'gold standard' in 30 patients with aortic or aortic valve disease. After validation, transverse 2D-CMR was used to assess ascending aortic dimensions in 65 patients with aortic bioprostheses, and the results were compared to those acquired with TTE. RESULTS: Data acquired with both 2D-CMR and 3D-MRA agreed well when assessing ascending aortic diameters (r = 0.99; p < 0.001; mean difference 0.1 +/- 0.1 cm). In patients with bioprostheses, the image quality was diagnostic in 100% of cases for 2D-CMR, and in 93.4% for TTE. The ascending aortic diameter by 2D-CMR (mean 3.8 +/- 0.5 cm; range: 2.6-5.0 cm) was larger (p < 0.001) than by TTE (3.3 +/- 0.6 cm; range: 2.3-4.9 cm). Aortic dilatation (diameter, indexed by body surface area, > 2.1 cm/m2) was present in 38.5% of 2D-CMR cases and in 11.5% of TTE cases. The intra- and inter observer variabilities to assess aortic dimensions by 2D-CMR were 2.1 +/- 1.9% and 4.3 +/- 3.7%, respectively. CONCLUSION: Imaging of the complete thorax in transverse orientation using fast, non-contrast-enhanced SSFP images provided an accurate and reliable approach to screen for aortic dilatation. In patients with aortic bioprostheses, 2D-CMR revealed a high prevalence of aortic dilatation, which was considerably underestimated by TTE. PMID- 20583399 TI - Planimetry of mitral valve stenosis in rheumatic heart disease by magnetic resonance imaging. AB - BACKGROUND AND AIM OF THE STUDY: To date, no investigations have been made on the role of magnetic resonance imaging (MRI) in evaluating mitral stenosis (MS) in Asian countries such as India, where rheumatic MS is more common. An accurate assessment of the mitral valve area (MVA) is particularly important when managing patients with valvular stenosis. Current standard techniques to assess the severity of MS include echocardiography and cardiac catheterization, the former of which represents the most practical approach. The study aim was to evaluate the accuracy and clinical utility of planimetry of the MVA and peak gradient, assessed by MRI in comparison with echocardiography, in rheumatic heart disease (RHD) patients with MS. METHODS: Among a group of 30 patients with suspected or known MS, planimetry of the MVA and mitral valve gradient (MVG) was performed with a 1.5 Tesla MRI scanner, using a breath-hold balanced gradient echo sequence (true FISP) and velocity-encoded MRI, respectively. The data obtained were compared with the echocardiographically determined MVA (ECHO-MVA). RESULTS: The correlation between the MRI-MVA and ECHO-MVA was 0.81 (p < 0.0001), and between the MRI-MVG and ECHO-MVG was 0.81 (p < 0.0001). The MRI-MVA slightly overestimated the ECHO-MVA by 8.1% (1.61 +/- 0.42 cm2 versus 1.48 +/- 0.42 cm2; p < 0.05). CONCLUSION: To the present authors' knowledge, this study is the first in which MRI has been used to evaluate MVA by planimetry, particularly in RHD. MRI is capable of adequately evaluating patients with rheumatic MS with respect to the peak gradient and MVA by planimetry. Thus, MRI planimetry of the mitral valve orifice in MS offers a reliable and safe method for the quantification of MS. Further studies are required to standardize the procedure in those patients with atrial fibrillation, or who are more symptomatic. PMID- 20583400 TI - Modified repair in patients with Ebstein's anomaly. AB - BACKGROUND AND AIM OF THE STUDY: Since 1988, a modified repair technique has been used at the authors' institution to treat patients with Ebstein's anomaly. This technique restructures the valve mechanism at the level of the true tricuspid annulus by using the most mobile leaflet for valve closure, without plication of the atrialized chamber. A total of 19 patients had additional attachment of the anterior right ventricular wall to the interventricular septum (Sebening's stitch) and reconstruction of the tricuspid valve as a double-orifice valve. The long-term results of the study are presented. METHODS: Between 1988 and 2008, tricuspid valve repair was performed in 50 patients with Ebstein's anomaly (33 females, 17 males; median age 22 years; range: 0.6 to 60 years), at the authors' institution. The median follow up was 68 months (range: 5 to 238) months. Details of the survival rate, reoperations, NYHA class, maximal VO2, right ventricular function (velocity-time integral pulmonary artery (VTI-PA)), and tricuspid valve insufficiency were documented. RESULTS: No patient deaths occurred during surgery; the early mortality was 7.1%, and late mortality 2.4%. Those patients who died were all aged > 50 years, and in NYHA class III or IV. No additional patient deaths have occurred since 2004. Four reoperations were necessary. Both, the NYHA class and tricuspid valve insufficiency were improved significantly (from 3.1 to 1.8; p < 0.001 and from 3.2 to 1.9; p < 0.001, respectively). The VTI-PA was increased significantly, with a stable heart rate (p = 0.01). No aneurysm of the right ventricle was observed. CONCLUSION: The long-term follow up demonstrated good clinical results in tricuspid repair, without plication of the right ventricle, even in cases where tricuspid valve replacement was discussed. Modifications seemed to support these results. Surgery in older patients with a progressive NYHA class seemed to carry a higher operative mortality. PMID- 20583401 TI - Supra-annular stitch to avoid distortion of the right coronary cusp in aortic root resuspension. AB - BACKGROUND AND AIM OF THE STUDY: The David procedure has been described in order to preserve the native aortic valve during correction of aortic root aneurysms, and to restore its competence in the case of aortic valve insufficiency. In general, the long-term stability of this procedure is very promising; any recurrence of aortic valve incompetence during follow up can be attributed mainly to a primary suboptimal geometry. METHODS: A distortion of the right coronary cusp was frequently observed after using the technique as originally described. This was due to the base of the right coronary cusp (RCC) being placed deeper in the left ventricular outflow tract than the adherent septal myocardium. By placing the central stitch at the right coronary base supra-annularly, the right coronary base is not rotated outwards after tying. RESULTS: This modification of the David procedure was carried out in 10 patients, with near-perfect valve geometry and competence. CONCLUSION: This technical modification represents a simple and safe way to avoid distortion of the RCC in aortic root resuspension. PMID- 20583402 TI - Rheumatic tricuspid valve disease: an evidence-based systematic overview. AB - BACKGROUND AND AIM OF THE STUDY: Right-sided valve abnormalities are less common than their left-sided counterparts. Furthermore, whilst organic rheumatic involvement of the tricuspid valve is not uncommon, it receives less attention than left-sided heart valves. An evidence-based systematic overview was carried out to assess the epidemiology, diagnosis and management of organic rheumatic tricuspid valve disease (RTVD) over the past half century. METHODS: A computed search spanning more than four decades was conducted to identify articles on various aspects of RTVD. The bibliographies of all relevant articles were also searched. RESULTS: A total of 2,497 rheumatic heart disease patients (mean age 25.5 years; female:male ratio 1.3:1) was included. RTVD was detected in 193 patients (7.7%). Echocardiography was used to detect tricuspid valve involvement in all patients. Associated mitral valve disease was present in 99.3% of the patients with RTVD. A total of 1,092 patients (mean age 45.4 years) was included from six studies on surgical correction of the tricuspid valve. Of these patients, 278 (25.4%) underwent tricuspid valve replacement, while 814 (74.5%) had tricuspid valve repair. The in-hospital mortality was 9.9%, and late mortality 33.2% CONCLUSION: RTVD is not uncommon among patients with rheumatic heart disease, but attracts less attention and might, therefore, be overlooked. Echocardiography is the most common diagnostic tool. Although indications for surgical intervention are not well defined, valve repair may have a better outcome than replacement. PMID- 20583403 TI - Pilot licensing after aortic valve surgery. AB - BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve is the most common congenital heart malformation, and a high percentage of patients with this condition will develop complications over time. It is rare that pilots undergo aortic valve surgery, and the confirmation of flight-licensing requirements after aortic valve replacement (AVR) is a challenge for the patient's cardiac surgeon and, particularly, for the Aeromedical Examiner (AME). Only AMEs are able to determine the flight status of pilots. Furthermore, in military and in civil aviation (e.g., Red Bull Air Race), the high G-load environment experienced by pilots is an exceptional physiological parameter, which must be considered postoperatively. METHODS: A review was conducted of the aeronautical, surgical and medical literature, and of European pilot-licensing regulations. Case studies are also reported for two Swiss Air Force pilots. RESULTS: According to European legislation, pilots can return to flight duty from the sixth postoperative month, with the following limitations: that an aortic bioprosthesis presents no restrictions in cardiac function, requires no cardioactive medications, yet requires a flight operation with co-pilot, the avoidance of accelerations over +3 Gz and, in military aviation, restricts the pilot to non-ejection-seat aircraft. The patient follow up must include both echocardiographic and rhythm assessments every six months. Mechanical prostheses cannot be certified because the required anticoagulation therapy is a disqualifying condition for pilot licensing. CONCLUSION: Pilot licensing after aortic valve surgery is possible, but with restrictions. The +Gz exposition is of concern in both military and civilian aviation (aerobatics). The choice of bioprosthesis type and size is determinant. Pericardial and stentless valves seem to show better flow characteristics under high-output conditions. Repetitive cardiological controls are mandatory for the early assessment of structural valve disease and rhythm disturbances. A pre emptive timing is recommended when reoperation is indicated, without waiting for clinical manifestations of structural valve disease. PMID- 20583404 TI - The association of heart valve diseases with coronary artery dominance. AB - BACKGROUND AND AIM OF THE STUDY: Aortic stenosis (AS) is thought to be caused by calcific degeneration of the aortic valve. Clinical observations suggest an association between a left dominant coronary circulation and AS, a situation previously investigated at necropsy and with small observational studies. Mitral regurgitation (MR) and aortic regurgitation (AR) are both disorders with multiple etiologies, but neither has any known association with coronary artery dominance. METHODS: The coronary angiogram database of a tertiary referral centre was reviewed for consecutive left heart catheter data acquired over a six-year period. The severity of AS was classified by measured pressure gradient (in mmHg) as none (0), mild (< 30), moderate (30-49), or severe (> 49). Both, MR and AR were assessed visually by the operator. RESULTS: A total of 1,891 patients was included. In the AS group there was a significant association with a left dominant coronary circulation (p < 0.0001), and the proportion of patients with left dominance increased with the severity of AS (p < 0.005). There was no significant association of AR with coronary artery dominance (p = 0.84). MR was associated with a reduced prevalence of left dominance (p < 0.005). CONCLUSION: AS was associated with a left dominant coronary circulation, and the incidence of left dominance was increased with the severity of AS, but the opposite situation was true for MR. The reasons for these observations remain unclear. PMID- 20583405 TI - Thrombocytopenia after aortic valve replacement: comparison between mechanical and biological valves. AB - BACKGROUND AND AIM OF THE STUDY: Concerns have been recently raised regarding the postoperative decrease in platelet count after aortic valve replacement (AVR). Thus, a retrospective analysis was conducted of patients after AVR with regards to postoperative platelet count. METHODS: The data were analyzed from all patients undergoing AVR with (n = 829) or without (n = 1,230) coronary artery bypass grafting (CABG) at a single center between January 1998 and May 2009. The lowest (minimum) platelet count within the first five postoperative days was determined. RESULTS: The patients received either an ATS mechanical prosthesis (ATS; n = 401), a St. Jude Medical mechanical prosthesis (SJM; n = 791), a Carpentier-Edwards Perimount bioprosthesis (CEP; n = 618), a Medtronic Freestyle stentless bioprosthesis (FRE; n = 213), or a Sorin Freedom Solo stentless bioprosthesis (SFS; n = 36). By using a multivariate linear regression model, the following independent risk factors for a lower postoperative platelet count were revealed: age, body surface area, active endocarditis, preoperative platelet count, duration of extracorporeal circulation, number of grafts, valve size, and units of transfused fresh-frozen plasma and red blood cells. On entering the type of prosthesis into the multivariate linear regression analysis, together with the other risk factors, patients with CEP and FRE valve prostheses had a lower minimum postoperative platelet count than those with mechanical prostheses (ATS and SJM). CONCLUSION: Patients undergoing AVR with the Carpentier-Edwards Perimount bioprosthesis or a Medtronic Freestyle stentless bioprosthesis had a lower minimum platelet count within the first five postoperative days, compared to patients receiving ATS and St. Jude Medical mechanical prostheses. No differences were identified between the Sorin Freedom Solo and all other valve prostheses. PMID- 20583406 TI - Puerperal endocarditis in an adult woman with congenital heart disease: a case report. PMID- 20583407 TI - Balloon dilatation of rheumatic tricuspid stenosis. PMID- 20583408 TI - Spontaneous resolution of severe hemolysis after valve surgery. PMID- 20583409 TI - Another cause of severe aortic regurgitation: congenital quadricuspid aortic valve. PMID- 20583410 TI - The effect of a new hemostatic agent for difficult cases of non-variceal gastrointestinal bleeding: Ankaferd blood stopper. PMID- 20583411 TI - Recurrence incidence of small HCC in cirrhosis patients by ablation versus injection. AB - BACKGROUND/AIMS: The incidence of local recurrence of hypervascular hepatocellular carcinoma (HCC) (15 mm or less) was compared retrospectively between a group treated with radiofrequency ablation (RFA) using cool-tip (Radionics, USA) 10-mm electrodes and a group treated with percutaneous ethanol injection (PEI). METHODOLOGY: There were 23 patients who were treated for a total of 25 tumors during a 3-year period at our hospital. Ten of the tumors (11.1 +/- 2.7mm) were treated with RFA using cool-tip 10-mm electrodes and 15 tumors (10.6 +/- 2.7 mm) were treated with PEI. After treatment, progression was evaluated in enhanced CT scans every 3-6 months to confirm presence or absence of local recurrence. RESULTS: The number of recurrences, mean observation period, and mean recurrence period in the RFA group were 2 (20%), 6.6 months, and 6 months. The number of recurrences, mean observation period, and mean recurrence period in the PEI group were 2 (13.3%), 19.1 months, and 18 months. The period between treatment and recurrence tended to be longer in the PEI group than in the RFA group to be significant p < 0.05. CONCLUSIONS: The results suggest that PEI treatment is more effective in local treatment of hypervascular HCC with tumor diameters of 15 mm or less. PMID- 20583412 TI - Lessons learnt after 12 years experience in laparoscopic cholecystectomy at a single center. AB - BACKGROUND/AIMS: This study was conducted to determine the results obtained with laparoscopic cholecystectomy (LC) at the Department of the First Minimal Invasive Surgery and Bile Duct Surgery, Sheng Jing Hospital of China Medical University. The authors compared current six years results with those at the former six years of the experience and developing a guideline. METHODOLOGY: Between May 1997 and May 2009, 2400 LCs were performed at the "Department of the First Minimal Invasive Surgery and Bile Duct Surgery, Sheng Jing Hospital of China Medical University"; 952 patients were operated on between May 1997 and May 2003, and 1,448 between Jun 2003 and May 2009. Data describing the peri-operative interventions, operative methods and maneuvers, complications and methods of preventing them was collected and analyzed. RESULTS: Mean hospital stay was 3.75 days. Conversion to open surgery was required for 0.46% of cases (11 patients). The surgical complication rate was 0.66%, with the most frequent being bile duct complications (0.42%) and bleeding (0.08%). Two patients died (0.08%). When the results (1997-2003 vs. 2003-2009) were compared, the differences in the history of a previous operation (30 vs. 23.8%, p = 0.001), role of the resident in LC (4.4 vs. 28.2%, p < 0.001), number of LCs for chronic calculous cholecystitis (52.42 vs. 66.16%, p < 0.001), for acute calculous cholecystitis (13.76 vs. 6.5%, p < 0.001) and for gallbladder polyp (32.76 vs. 26.45%, p = 0.001) and mean hospital stay (4.65 vs. 2.85 days, p = 0.034) was observed. In the latter 1448 cases (60.3%), LC was done without the need for routine urinary catheter or gastric tube insertion. CONCLUSIONS: These results should be interpreted with caution as this is a retrospective study with much uncontrolled bias. We can rely on our practice to accumulate and summarize our experience to formulate perioperative interventions, gradually develop routines management protocols and shorten the learning curve. PMID- 20583413 TI - Expression of LAPTM4B in gallbladder carcinoma cells: the role in invasive potential. AB - BACKGROUND/AIMS: It was previously established that LAPTM4B-35 highly expressed in gallbladder carcinoma and being of clinicopathological and prognostic significances. However, expression of LAPTM4B gene in gallbladder carcinoma (GBC SD), a gallbladder carcinoma cell line, and its role in invasive potential remain unclear. METHODOLOGY: Expression of LAPTM4B in GBC-SD cells was first detected. Plasmids, pcDNA3-AE (containing complete open reading frame of LAPTM4B) and Mock (pcDNA3), were transiently transfected into GBC-SD cells. Invasive phenotypes (migration and invasion) and relative molecules were then shown by transwell assay, crossing river test and Western blot analysis. RESULTS: Immunocytochemical staining revealed that LAPTM4B-35 positively expressed in cytoplasm of GBC-SD cells. But LAPTM4B-35 expression was obviously weaker in GBC-SD cells than that in BEL-7402 cells (positive control). Besides, cells transfected with pcDNA3-AE presented shorter crossing river time, less migrated and invaded cell numbers, compared with cells transfected with the Mock plasmid and parent cells. Finally, increased expressions of active uPA, MMP-9, pro MMP-2 and active MMP-2 were also observed in cells transfected with pcDNA3-AE. CONCLUSIONS: Our data suggested that LAPTM4B expressed in GBC-SD cells at a relatively low level. Forced overexpression of LAPTM4B increased invasive potential of GBC-SD cells, through modulating molecules associated with degradation of extracellular matrix. PMID- 20583414 TI - Agenesis of the gallbladder with adipose tissue in the gallbladder fossa. AB - Agenesis of the gallbladder with normal bile ducts is a rare anomaly. More cases have been reported preoperatively because of the increased awareness of this entity. However some cases remain difficult to diagnosis. We report such a case. A symptomatic male patient (age 45) was diagnosed with chronic atrophic cholecystitis and cholecystlithiasis by ultrasonography and computed tomography scan. The images revealed solid tissue in the gallbladder fossa. However, during laparoscopic exploration no gallbladder or ectopic gallbladder was found. Only adipose tissue and the gallbladder artery were identified during the operation. Gallbladder agenesis was diagnosed postoperatively. It still remains a challenge to determine surgical intervention in these cases. PMID- 20583415 TI - Facing the challenge of treating gallbladder carcinoma. Review of the literature. AB - Gallbladder carcinoma (GBC) remains the most common biliary tract malignancy and is characterized as an aggressive and highly lethal disease. There is also a wide discrepancy among sources regarding the epidemiology of the tumor. Despite recent research on the therapeutic strategies against gallbladder neoplastic disorders, surgical resection appears the only potentially curative approach. Unfortunately, a mere minority of patients is eligible to undergo surgical intervention. In addition, surgical removal of gallbladder tumor does not necessarily guarantee patient's long-term recovery. Alternative therapies, such as radio and chemotherapy proved insufficient. The aim of this review was to evaluate the results of surgical treatment for GBC with special reference to the extent of its histological spread and to present the recent literature in order to provide an update on the current concepts of surgical management of the disease. PMID- 20583416 TI - Significance of defecography in the diagnosis and evaluation of male patients with defecation disorders. AB - BACKGROUND/AIMS: There are few reports on defecography in male patients with defecation disorders (DD) such as morphological and functional abnormalities (MFA) in the anorectal region. To clarify the significance of defecography in male patients with DD, defecography was performed in the diagnosis and evaluation of DD. METHODOLOGY: The subjects of this study included 37 male patients with DD (group A; aged 15 to 73 years, average 46.5 years). As a control (group B), 30 male healthy volunteers (aged 26 to 66 years, average 46.9 years) were also examined. To perform defecography, we used a plastic pot placed on the elevated footrest of an X-ray table, and evaluated the findings of defecography. A contrast medium (a mixture of barium and wheat flour) was infused into the rectum. RESULTS: In group A, the incidence of a sense of incomplete emptying of the rectum was significantly greater than that in patients with chronic constipation, difficulty in bowel emptying, perineal pain with defecation, and discomfort in the perineal region (p = 0.0483, p < 0.0001, p < 0.0001, p < 0.0001, respectively). The incidence of bowel habits (once per day) in group B was significantly greater than that that in group A (p < 0.0001). The incidence of defecation with straining in group A was significantly greater than that in group B (p < 0.0001). In group A, the incidences of abnormalities of the levator muscles and abnormalities of the levator muscle with abnormalities in the rectal wall were significantly greater than abnormalities of the rectal wall (p = 0.0049) and normal defecogram (p = 0.1022). The incidence of the normal defecogram in group B was significantly greater than that in group A (p < 0.0001). CONCLUSIONS: Defecography clearly showed MFA in male patients with DD. Defecography is useful for the diagnosis and evaluation of the MFA in male patients with DD. PMID- 20583417 TI - Endoscopic submucosal dissection using a novel vibration endoscopy. AB - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) technique requires special skill and involves a prolonged procedure time. Therefore, the present study aim is to increase the efficiency of endoscopic treatment techniques by vibrating the endoscope scope itself. The usefulness of this vibration endoscopy for ESD was evaluated in 6 porcine stomachs. METHODOLOGY: Vibration endoscope modified a commercial endoscope (Olympus: GIF-Q200). Investigations to measure procedure time were conducted separately with and without vibration of 5,000 or 10,000 rpm applied at the time of circumferential incision and submucosal dissection. RESULTS: Among circumferential incisions, submucosal dissection and a total of both, the average procedure durations with vibration at 10,000 rpm were significantly shorter than that without vibration. CONCLUSION: When performing peripheral incisions and submucosal dissection with a knife in ESD, the time for the procedure was reduced by adding vibration. PMID- 20583418 TI - Elucidating therapeutic effects on patients with hepatocellular carcinoma and main portal vein thrombosis. AB - BACKGROUND/AIMS: The survival duration for patients diagnosed with hepatocellular carcinoma (HCC) with main portal vein thrombosis (MPVT) was usually less than 3 months. The aim of this study is to elucidate whether treatment can prolong the survival for such patients. METHODOLOGY: Retrospectively we analyzed the clinical features and outcomes of 63 patients with HCC and MPVT over a 7-year period. Three therapeutic modalities--transcatheter arterial chemotherapy (TAC) with or without radiotherapy (RT), and systemic chemotherapy--were applied. RESULTS: The patients were divided into two groups: 34 (54%) patients were treated, while the remaining 29 (46%) were not. Multivariate analysis revealed that Child-Pugh class, Okuda stage for HCC and the presence of treatment were the principal factors to predict survival. The survival was significantly longer in treated patients than those untreated both in the Child-Pugh class A or B patients. Significantly longer survival is evident in patients treated by TAC combing RT compared to those underwent TAC alone, systemic chemotherapy or no treatment. CONCLUSIONS: The survival of Child-Pugh class A or B patients can be extended by the use of an appropriate therapeutic modality. TAC combined with RT did the best benefit to prolong survival in such patients. PMID- 20583419 TI - Laparoscopic versus open restoration of intestinal continuity after Hartmann procedure. AB - BACKGROUND/AIMS: To present the initial experience with laparoscopic technique of restoration after Hartmann procedure compared to open surgery. METHODOLOGY: All patients submitted to Hartmann procedure from 2003 to 2008 were considered. The following parameters were evaluated: age, gender, comorbidities, American Society of Anesthesiologists score, indication for the procedure, Hinchey scale, interval between Hartmann and reversal procedure, total operative time of Hartmann reversal, pain management, delay in renewal of peristalsis, start of alimentation, length of hospital stay, morbidity, and mortality. RESULTS: Six patients were divided into groups A and B. Patients in group A underwent open Hartmann reversal and patients in group B underwent laparoscopic Hartmann reversal. Mean operative time was 136,6 min for group A and 95,6 min for group B. Mean postoperative duration of nasogastric tube placement was 2 days for group A and 1 day for group B. Group B showed a earlier return of bowel function and earlier restart of alimentation. Group B had shorter length of stay. There was no mortality or morbidity. CONCLUSIONS: Laparoscopic approach showed a shorter mean postoperative nasogastric tube time of placement and a shorter mean hospital stay, with faster resumption of bowel movements and early solid diet alimentation. PMID- 20583420 TI - Neuroendocrine tumours--analysis of own material--a nine--year retrospective study. AB - BACKGROUND/AIMS: Neuroendocrine tumours are fairly rare neoplasms that require different treatments and have various prognoses. The aim of this study was to present the author's observations of the histological tumor types, occurrence and its surgical treatment. METHODOLOGY: Thirty-five cases of neuroendocrine tumours were studied retrospectively in a 9-year period. All cases were investigated for haematological and biochemical parameters. Ultrasonography, scintigraphy, computed tomography or magnetic resonance imaging of abdominal cavity, pelvis, thorax or neck--depend on the tumor localization--were done in every individual. All cases were subjected to surgical procedure with an aim to resect the tumour completely. RESULTS: In the present study were observed 6 cases of carcinoids localized in ileum, cecum and sigmoid colon, 1 case of gastrinoma in pancreatic head localization, 1 case of insulinoma localized in pancreatic tail, 1 case of vipoma localised in pancreatic head, 2 cases of nesidioblastoma and 1 case of microcystic adenoma with neuroendocrine differentiation in pancreatic tail localization and 1 case of nonspecific apudoma observed in ileum. There were 6 cases of neuroendocrine tumours localized in pancreas. In the study we have also 11 cases of medullary thyroid carcinomas. In adrenal glands we observed 10 benign and 1 malignant pheochromocytoma (one bilateral female case with Multiple Endocrine Neoplasia type 2A). CONCLUSIONS: Neuroendocrine tumours occur very rare. Their clinical course makes recognition difficulties and as a result they are usually quite extensive when first detected. The clinical manifestations of some neuroendocrine tumours are not specific, so it causes a lot of difficulties in early diagnosis and treatment. PMID- 20583421 TI - Entecavir for hepatitis B virus flare treatment in patients with Crohn's disease. AB - Chronic hepatitis B virus (HBV) infection is a global health problem and has an increased prevalence in patients with Crohn's disease due to their increased requirement for high-risk procedures. A balance between viral replication and host immune response exists and drugs such as the immunosuppressive agents used to treat Crohn's disease may alter this balance. These may result in a hepatic flare, which manifests as high viremia, increased transaminase levels, and hepatic decompensation. The present study describes two cases of hepatic flare thought to be caused by treatment of acute Crohn's disease with systemic corticosteroids and/or azathioprine. Both patients presented with raised transaminase and gamma glutamyl transferase levels and viremia. One patient experienced a decrease in hepatic function, as evidenced by a reduced serum albumin (2.5g/ dL) and jaundice (total bilirubin 5.2 mg/dL), and hepatic decompensation, with ascites. Both patients were treated with the nucleoside analogue entecavir 0.5 mg/day and experienced reductions in HBV-DNA and hepatic enzyme levels within 4-7 days. The patient with decompensation received diuretic therapy and parenteral nutrition to support hepatic function and a clinical improvement was seen. Both patients were discharged 2 weeks after admission and, during follow-up, HBV-DNA levels became negative after 1 and 5 months, respectively. No adverse events were reported in either patient. To the best of our knowledge, this is the first documented report of treatment of HBV flare with entecavir in patients co-affected with Crohn's disease. PMID- 20583422 TI - Preoperative radiotherapy of rectal cancer--influence of fractionation and dose. AB - BACKGROUNDS/AIMS: We have been focused on patients with preoperative irradiation and compared two modes of radiotherapy, short-term (15 days) and long-term (45 days). METHODOLOGY: Monitored group of 183 patients who had undergone a preoperative irradiation between 01/01/1998 and 12/31/2002 were irradiated in two modes: with a dose of 45Gy applied in 25 fractions/1.8Gy per fraction (CFD45) and a dose of 34.5Gy in 15 fractions/2.3Gy per fraction (CFD34.5). RESULTS: No statistically significant difference in the occurrence of acute and postoperative complications, of locoregional recurrences and secondary dissemination, was mentioned in either group. In patients irradiated with CFD34.5 amputation of the rectum followed in 55%, and unlike the group irradiated with CFD45 the percentage of amputations was significantly lower (42%). We have recorded the average 5-year overall survival (OS) in those irradiated with CFD4.5 in 54% versus 61% in those irradiated with CFD45. More considerable conclusion was made comparing a 5-year disease-specific survival (DSS) versus the mode of irradiation, CFD34.5 57%, versus CFD45 71%. The significance level reached 10% (p = 0.057). CONCLUSIONS: Pre-operative irradiation of the rectal cancer with the dose of 45Gy in 25 fractions/dose of 1.8Gy per fraction is a standard recommended procedure. PMID- 20583423 TI - The role of pRB, p16 and cyclin D1 in colonic carcinogenesis. AB - BACKGROUND/AIMS: This study is aimed to investigate abnormal expression of the Rb protein (pRb), p16(INK4a) (p16) and cyclin D1 in colorectal adenomas and adenocarcinomas and to assess the possible alterations in Rb pathway in colorectal carcinogenesis. METHODOLOGY: 44 cases of colorectal adenoma and 44 cases of colorectal adenocarcinoma were examined histopathologically and immunohistochemically using monoclonal antibodies to identify abnormalities of pRb, p16, and cyclin D1 expression. Staining degree of above-mentioned markers was assessed by using a semi-quantitative method in all cases in order to determine any staining differences. RESULTS: In 70.5% of the adenomas and 97.7% of the adenocarcinomas, an overexpression of pRb was found. There was a statistically significant relationship between the immunoreactivity of pRb and villous/tubulovillous types of adenomas (p < 0.05). There was a loss of p16 expression in 84.1% of adenomas and 61.4% of adenocarcinomas. Statistically significantly, the p16 overexpression was not seen in any of tubular adenomas (p < 0.001). Overexpression of cyclin D1 was found in only 9.1% of adenomas, while 31.8% of adenocarcinomas overexpressed this protein. Loss of expression of cyclin D1 was similar in adenomas and adenocarcinomas (27.3% and 25%, respectively). Staining degrees of all three cell cycle proteins were shown to be statistically different in adenomas and adenocarcinomas, for pRb (p = 0.001), for p16 ( p = 0.045), and cyclin D1 ( p = 0.05). Also, there was only a mild agreement with respect to p16 and cyclin D1 relationship between for adenomas ( K = +0.28 p = 0.051) and for adenocarcinomas ( K = +0.35 p = 0.017). Besides, there was no correlation between the expression of pRb, p16, and cyclin D1 and clinicopathological tumor characteristics and prognostic data such as stage or lymph node/liver metastasis. CONCLUSIONS: pRb, p16 and cyclin D1 are shown to be aberrantly expressed in both colorectal adenomas and adenocarcinomas. It can be claimed that disturbances in Rb pathway take part in colonic carcinogenesis and pRb, p16 and cyclin D1 play an ever increasing role in the further stages of adenoma-carcinoma sequence. PMID- 20583424 TI - GABARAP is overexpressed in colorectal carcinoma and correlates with shortened patient survival. AB - BACKGROUND/AIMS: Gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP), the mammalian homologue of yeast Atg8, is involved in autophagosome formation during autophagy. The aim of this study is to explore the expression and its prognostic significance in comparison with various clinicopathological predictors of survival. METHODOLOGY: GABARAP protein expression was determined by immunohistochemistry in 103 colorectal cancers. Cytoplasmic immunoreactivity was scored semiquantitatively. The results were analyzed in correlation with various clinicopathological variables, including patient survival. Chi-square test and Kaplan-Meier survival analysis were applied. RESULTS: The expression of GABARAP was significantly higher in colorectal cancers than that in adjacent matched nontumor tissues (51.5% vs 33.0%, p < 0.01). Increased expression of GABARAP expression in colorectal cancers was significantly correlated with a low grade of differentiation and shortened overall survival (p < 0.05). There were no significant differences between the expression of GABARAP and age, gender, stage, tumor size, location of primary tumor, and lymph node invasion. CONCLUSIONS: Our data demonstrated that GABARAP is frequently expressed in colorectal cancer. Overexpression of GABARAP is a new independent prognostic marker, which is associated with poor differentiation as well as shortened overall survival. PMID- 20583425 TI - Ligation of oesophageal varices may increase formation of "deep" gastric collaterals. AB - BACKGROUND/AIMS: Endosonography (EUS) is rarely used in the routine diagnostic of portal hypertension in patients with cirrhosis even though it has significantly higher sensitivity for detection of varices than gastroduodenoscopy. The aim of this cross-sectional study was to assess the features of portal hypertension identified with EUS and to analyze the effect of variceal ligation on the prevalence of "deep" varices in subjects with cirrhosis. METHODOLOGY: A cohort of 121 patients was divided into 2 groups depending on whether they had a history of variceal bleeding treated with ligation or not. RESULTS: "Deep" oesophageal varices and large (> 5 mm) gastric varices occurred significantly more common in patients with previous banding. Also, large "deep" gastric varices occurred significantly more common in the banded group with no or small varices than in the not-banded group with similar endoscopy. Sixty percent of banded patients who had grade II/III oesophageal varices on endoscopy had large "deep" gastric varices comparing to 20% of not-banded with the same endoscopical findings (p = 0.04). CONCLUSION: Previous banding may increase the risk of the development of large "deep" oesophageal and gastric varices. Thus potential new indication for EUS in patients with cirrhosis could be a follow-up examination after successful eradication of varices. PMID- 20583426 TI - Quality of small bowel preparation for video-capsule endoscopy. Prospective comparison of two different preparations. AB - BACKGROUND/AIM: The best preparation for successful small bowel video-capsule endoscopy (VCE) is still unknown. The primary aim of our study was to compare sodium phosphate (PS) and polyethylene glycol (PEG) purge on the quality of small bowel preparation. METHODOLOGY: In this prospective, non-randomized, two centers study, we evaluated 47 and 48 consecutive outpatients who received PS and PEG preparations, respectively. Two independent investigators measured the proportion of small bowel transit time (SBTT) without clean mucosa. Two other investigators assessed bowel preparation independently, using a visual analogue scale (VAS). RESULTS: The proportion of SBTT without clean mucosa was similar for both preparations, in the proximal [3.8 (2.1-8.7) % vs. 4.85 (2.7-9.7) %, p = 0.24)] and in the distal half [31.9 (10.7-52.5) % vs. 22.9 (6.9-57.7) %, p = 0.48] of VCE recording. There was moderate - good correlation of VAS assessment of bowel preparation with the proportion of SBTT without clean mucosa in the proximal (r = 0.69, p < 0.001) and in the distal half (r = 0.76, p < 0.001) of the recording. The outcome measures of the studies were similar for both preparations. CONCLUSIONS: PS and PEG preparations result in similar quality of small bowel preparation and similar outcome measures of VCE studies. VAS assessment could be an alternative measure of bowel preparation in clinical practice. PMID- 20583427 TI - Three common CARD15 mutations are not responsible for the pathogenesis of Crohn's disease in Iranians. AB - BACKGROUND/AIMS: Crohn's disease frequency has increased in recent years in Iran. Genetic and environmental factors predispose people to this disease. Mutation in Caspase Recruitment Domain 15 (CARD15) gene is the most well known genetic predisposing factor to this disease. Frequency of three common CARD15 mutations has been studied in different ethnic groups. We aimed to study the frequency of these mutations in Iranian patients affected with Crohn's Disease. METHODOLOGY: One hundred fifteen proved cases of Crohn Disease and 115 age and sex matched normal controls were recruited in this study. Lf1007fs, R702W and G908R mutations were studied by Polymerase Chain Reaction-Restriction Fragment Length Polymorphims (PCR-RFLP) followed by sequencing the positive cases. RESULTS: Lf1007fs and G908R mutations were not found in either patients or age-sex matched controls. Just in two patients, R702W mutation was proved by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing. None of these patients had illeal or fibrostenotic type of disease while 14.7% of total patients had stricturing type of disease. No complication was seen in these two patients while 50.4% of patients had acquired complications during the course of disease. CONCLUSION: The three mutations described are not responsible for the pathogenesis of Crohn's Disease in Iranians. The results are in accordance with other Asian nations' studies on IBD Patients. PMID- 20583428 TI - Predictive factors of azathioprine prescription in adult patients with Crohn's disease. AB - BACKGROUND/AIMS: Azathioprine is the most commonly used immunomodulator in Crohn's disease. The aims of the study are to determine the cumulative frequency of azathioprine prescription in non selected consecutive inpatients with Crohn's disease and to identify a subgroup of patients with high risk of azathioprine prescription during the follow-up. METHODOLOGY: We studied consecutive in patients with established diagnosis of Crohn's disease admitted in our department in years 2002 and 2003. Cumulative frequency of azathioprine use during the follow-up was calculated. Predictive factors of azathioprine use were studies based on clinical, biological and endoscopic charts at the first hospitalization in our department. RESULTS: We include 88 patients (52 males, mean age 31.3 years (18 - 68)). Azathioprine was prescribed in 38 patients (43.2%) with a mean period of 12.9 months (1 - 90) after the first hospitalization. The cumulative frequency of azathioprine prescription was 11% the first month, 31% at 6 months, 35% at one year and 49% at 6 years. In univariate analysis, azathioprine use was more frequent in previously treated patients in an other department (p = 0.05), in case of ileal involvement > 40 cm (p = 0.02), previously treated patients with corticosteroids (p = 0.001), first treatment in our unit by corticosteroids (p < 0.0001), duration of the flare more than 6 months (p = 0.01), CDAI > 204 points (p < 0.0001), Hemoglobin level < 9.7 g/ dl (p < 0.0001) and cholesterolemia level < 1.32 g/l (p < 0.0001). Independent factors associated with azathioprine use in our population were diffuse involvement of the ileum at initial hospitalization (p = 0.0001; OR [95%CI]: 17.9 [4.1-77.9]), and previous prescription of corticosteroid therapy (p = 0.04; OR [95% CI]: 5 [1.1-25]). CONCLUSION: Azathioprine is frequently used in adult Crohn's disease patients, maximally within the first year after the first hospitalization. Patients with diffuse ileal involvement and previously treated patients with corticosteroids are at higher risk to azathioprine use and should have systematically the preventive strategies to ovoid opportunistic infections since their first visit. PMID- 20583429 TI - Nonfunctional retroperitoneal paraganglioma presenting as acute upper gastrointestinal hemorrhage. AB - Paragangliomas are very rare tumors arising from extraadrenal chromaffin cells. Clinical presentation of benign retroperitoneal nonfunctional paraganglioma is unspecific. Symptoms may occur when tumor attains a remarkable size or when complications arise. This article reports a case of nonfunctional retroperitoneal paraganglioma as a cause of acute upper gastrointestinal hemorrhage which represents the unusual urgent clinical manifestation of these tumors. The presented case emphasizes the necessity to include extraadrenal paraganglioma in the differential diagnosis in all patients with retroperitoneal mass found even in the presence of at first appearance non-related emergency condition like acute upper gastrointestinal bleeding. PMID- 20583430 TI - Octreotide therapy for hepatocellular carcinoma: a systematic review of the evidence from randomized controlled trials. AB - Currently no standard treatment for patients with advanced hepatocellular carcinoma (HCC), and available literature assessing octreotide's treatment effect on HCC reports discordant results. The primary purpose of this study was to evaluate the effect of octreotide therapy on patient survival. The secondary endpoints were to assess tumor response, quality of life and adverse effects. PUBMED, MEDLINE, OVID and SPRINGER databases were searched through January 2009. Randomized controlled trials that compared octreotide treatment with placebo or no treatment were selected. Finally, four randomized controlled trials (three of which were high quality trials) published in 1998 or later with a total of 373 patients were included in this review. Because a significant clinical heterogeneity existed between the included trials, making meta-analysis inappropriate; only a narrative systematic review was performed. Of the three high-quality trials, only one(126 patients) reported octreotide could improve survival and quality of life of HCC patients, whereas the other two(189 patients) suggested octreotide did not have survival benefit in HCC; moreover, none of the three trials indicated that octreotide has significant beneficial effect on tumor regression or decrease of tumor mass. Nonetheless, serious adverse effects were not reported in these included trials. In this review, results from included randomized controlled trials demonstrated no clear benefit of octreotide therapy in advanced HCC patients. In order to detect a realistic treatment advantage, further larger well-designed multicenter randomized trials will have to be conducted. PMID- 20583431 TI - Detection of hepatitis C virus (HCV) in body fluids from HCV monoinfected and HCV/HIV coinfected patients. AB - BACKGROUND/AIMS: The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is supported by the demonstration that the actual virus is present in several body fluids. In this study, we investigated the relationship between the detection of HCV RNA in body fluids (saliva, cervical smears, seminal fluid and peripheral blood mononuclear cells) from chronically HCV-infected patients and several viral and host factors. METHODOLOGY: This study comprised 16 HIV/ HCV coinfected and 21 HCV monoinfected patients with a median age of 38 and 45 years, respectively. HCV-RNA was detected in serum and fluids samples by reverse transcription-nested polymerase chain reaction. Genotypes were determined by using RFLP and direct nucleotide sequencing of the PCR products and plasma viral loads by using NASBA HCV-QT. RESULTS: When compared on the basis of the results of the detection of HCV-RNA in fluids, patients did not differ significantly in relation to viral load, genotype, HCV/HIV coinfection, and epidemiological host factors. CONCLUSIONS: Our data suggest that HCV can be detected in body fluids of chronically HCV-infected patients independent of these cofactors, including circulating HCV load and HCV/HIV coinfection. Studies on HCV dynamics are needed to gain insights into nonparenteral transmission of HCV. PMID- 20583432 TI - Esophagogastric varices predict mortality in hospitalized patients with alcoholic liver disease in Taiwan. AB - BACKGROUND/AIMS: Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in Western countries. The present study investigated the status and the risk factors for predicting mortality of ALD in Taiwan. METHODOLOGY: We retrospective studied 100 consecutive in patients with ALD between 1992 and 2000. All patients had a history of alcohol consumption exceeding 80 g per day for at least 5 years. RESULTS: The study comprised 93 men and 7 women with a mean age of 45.4 years. The ALD included fatty liver (21%), alcoholic hepatitis (15%), alcoholic hepatitis superimposed on alcoholic cirrhosis (24%), and alcoholic cirrhosis (40%). Forty-four percent of patients had esophagogastric varices. Thirty-three percent of patients were mortality. The presence of esophagogastric varices was the only parameter identified by univariate and multivariate analyses and had a statistically significant association with increased mortality (OR: 8.603; 95% CI: 2.009-36.864; p = 0.004). The cumulative survival for ALD patients with varices was significantly lower than for patients without varices. CONCLUSIONS: The presence of esophagogastric varices had a statistically significant relationship with increased mortality. This study strongly implicates esophagogastric varices were a valuable poor prognostic factor with mortality. Upper gastrointestinal endoscopy is a simple clinical available tool for the assessment of the occurrence of varices to predict the disease severity and mortality in hospitalized patients with ALD. PMID- 20583433 TI - Insulin resistance in liver cirrhosis. AB - BACKGROUND/AIMS: Liver cirrhosis is a chronic disease by degeneration, regeneration and fibrosis in the liver parenchyma, caused by many diseases. Insulin resistance can be defined as any type of decrease in the effect that may occur at the phases following insulin's secretion from beta-cells of the pancreas, where it is produced, until it has the expected effects in the target cells. The aim of the present study is to demonstrate the presence of insulin resistance in LC, which is common in our country and region, and investigate the existence of association between insulin resistance occuring in LC and cytokine levels, age, gender, CRP, Hs-CRP, Child-Pugh score and etiology of LC. METHODOLOGY: A total of 79 patients with liver cirrhosis (group 1) were included in the study, and 50 subjects as controls (group 2). Of liver cirrhosis patients, 49 (62%) were male and 30 (38%) were female, with a mean age of 54.71 +/- 14.68. Of the controls, 23 (46%) were male and 27 (54%) were female, with a mean age of 41.9 +/- 11.54. Severity of cirrhosis was assessed by Modified Child-Turcoutte Pugh score. Seven cases (8.9%) were at the Child-Pugh stage A, 35 cases (44.3%) at the Child-Pough stage B, and 37 cases (46.8%) at the Child-Pough stage C. HOMA IR was calculated and values > 2.7 were regarded as presence of insulin resistance (HOMA-IR +). Serum glucose, albumin, bilirubin values were studied with enzymatic method (Architect C-16000); serum CRP, Hs-CRP values with nephelometric method by Beckman Coulter Image Nephelometer (immunochemistry system); insulin, C-peptide with electrochemiluminance immunological method; prothrombin time with radiation method by ACL-Advance brand device. RESULTS: In this study, glucose (p = 0.004), insulin (p = 0.010), C-peptide (p < 0.001), HOMA IR (p < 0.001), TNF-alpha (p < 0.001), IL-2RES (p < 0.001), IL-6 (p = 0.002), CRP (p < 0.001) and HsCRP (p = 0.006) levels are elevated in LC patients, compared to control group. Consequently, high HOMA-IR in LC supports the fact that insulin resistance develops in LC, as it is reported in similar studies. When HOMA-IR positive and negative patients within LC patients are compared, it is seen that insulin resistance develops independently of age, etiology, gender, Child-Pugh classification, spleen size, TNF-alpha, IL-16, IL-2RES, IL-6, IL-10, CRP, Hs-CRP (p > 0.05) levels. PMID- 20583434 TI - ADAMTS13 activity decreases after hepatectomy, reflecting a postoperative liver dysfunction. AB - BACKGROUND/AIMS: The precise mechanism and prophylactic strategy of deteriorated hepatic function after liver surgery have not been fully understood. The substrate of ADAMTS13, unusually large von Willebrand factor multimers, is produced in vascular endothelial cells at liver injury, leading to platelet aggregation. The decrease of plasma ADAMTS13 activity may involve not only the formation of platelet thrombi in the liver, but also subsequent progression of liver dysfunction through a microcirculatory disturbance. This study evaluated changes of plasma ADAMTS13 activity and its clinical relevance in patients with hepatectomy. METHODOLOGY: Plasma ADAMTS13 activity and its related parameters were sequentially determined after hepatectomy in 70 patients. RESULTS: ADAMTS13 activity significantly decreased preoperative 67.0 +/- 30.6 to 48.1 +/- 24.6% after hepatectomy (p < 0.0001). Pringle's maneuver for longer than 45 minutes (p = 0.0007) and major hepatectomy (p = 0.0002) were significantly associated with the decrease of ADAMTS13 activity to less than 40%. The decreased ADAMTS13 activity reflected postoperative thrombocytopenia (p = 0.0028) and hyperbilirubinemia (p < 0.05). CONCLUSIONS: Plasma ADAMTS13 activity significantly decreased after hepatectomy due to ischemic injury together with liver mass reduction, reflecting a postoperative liver dysfunction. Monitoring of ADAMTS13 activity may be useful to prevent further development of the liver failure after hepatectomy. PMID- 20583435 TI - May the method of hepatic parenchymal transection influence early results of liver surgery? AB - BACKGROUND/AIMS: Aim of this work was to analyze retrospectively two groups of patients who underwent hepatic resection using two different techniques, to determine whether exists a difference in hepatic tolerance and in the early outcome. METHODOLOGY: We retrospectively analyzed seventy-one patients divided into group 1, treated with kellyclasia and Pringle maneuver, and group 2 treated with a radiofrequency device. The following parameters were analyzed: age; sex; type of disease, number of major/minor resections; total operative time and transection time; number and time of clampings; blood loss; pre- and postoperative transaminases and total bilirubin; length of hospitalization; morbidity and mortality. RESULTS: Median total operative time and median hospital stay were similar in both groups but median median blood loss was higher in group 1. ALT levels in group 1 were higher than in group 2. Morbidity and mortality were observed only in group 1. CONCLUSIONS: Kelly-crush is related to a lower parenchymal tolerance as shown by the higher increase in postoperative alanine aminotransferase levels. PMID- 20583436 TI - Deep cholestatic jaundice as the predominant manifestation in autoimmune hepatitis. AB - Autoimmune hepatitis is a chronic liver disease of unknown etiology. The diagnosis is based on the exclusion of other liver diseases such as drug-induced liver disease, alcohol liver disease, viral liver diseases and so on, characterizing by elevation of transaminases, hypergammaglobulinemia, auto antibodies and the histological features of interface hepatitis and plasma cells infiltration. However, deep cholestatic jaundice as the initial presentation, with elevated serum transaminases one month later, is rare in autoimmune hepatitis. We described a case of type 1 autoimmune hepatitis with deep cholestatic jaundice and hyperbilirubinemia as the initial predominant manifestation. It demonstrated that the cholestasis can also occur as the initial predominant syndrome in autoimmune hepatitis and respond well to the treatment with the glycyrrhizin and ursodeoxycholic acid. PMID- 20583437 TI - A hepatic metastasis from pleomorphic adenoma of salivary gland: an unusual presentation. AB - Metastasizing pleomorphic adenoma (PA) is a rare condition displaying benign histological features as of PA in the metastatic lesion. The present study report a case of 46 years old male presented with space occupying lesion in the right lobe of liver. Patient underwent extended right hepatectomy for space occupying lesion in liver and the histological features were suggestive of metastatic benign pleomorphic adenoma. Surgical resection is the treatment of choice for both primary and metastatic lesion. PMID- 20583438 TI - Acute seronegative autoimmune hepatitis. AB - A 52-year-old woman who had some atypical features of autoimmune hepatitis is described here. Acute presentation, negativity of all autoimmune markers and the features of multiple acinar confluent necrosis were interesting findings. She had a complete resolution under standart immunosuppressive therapy. PMID- 20583439 TI - Comparison of outcome of hepatectomy with thoraco-abdominal or abdominal approach. AB - BACKGROUND/AIMS: Thoraco-abdominal approach is a suitable choice for hepatectomy to secure good view for mobilization. The aim of this study was to assess efficacy of thoraco-abdominal approach (TAA) for hepatectomy. METHODOLOGY: There were compared clinicopathological data, surgical results and postoperative complications of 425 consecutive patients who underwent hepatectomy via abdominal (AA) (n = 147) or TAA (n = 278). RESULTS: Blood loss and operating time were significantly higher in TAA than AA group (970 vs. 830 ml and 408 vs. 372 min.) (p < 0.05). Prevalence of pleural effusion was significantly higher in TAA than AA group (24 vs. 9%) (p < 0.01). However, proportions of patients who developed hepatic complications such as biloma (14 vs. 23%), and wound infection (8 vs.25%) were significantly less in TAA than AA group (p < 0.05). Hospital stay after hepatectomy and mortality were similar between both groups. Presence of chronic viral hepatitis, lower platelet count, higher level of serum hyaluronic acid, larger blood loss and TAA correlated significantly with thoracic complications (p < 0.05). Multivariate analysis showed that increased blood loss (p = 0.011), but not TAA, was a significant determinant of thoracic complications (p = 0.08). CONCLUSIONS: TAA can be considered a relatively safe approach for hepatectomy with minimal abdominal complications nevertheless of frequent pleural effusion. PMID- 20583440 TI - Neuroendocrine tumors of pancreas: how can we apply the 2006 TNM proposal? AB - BACKGROUND/AIMS: In 2006, a TNM system for foregut neuroendocrine tumors has been proposed. Our study aimed to present the management of neuroendocrine tumors of pancreas according to this classification and to highlight some of its limitations. METHODOLOGY: Clinical, biochemical, radiological, surgical and pathological data were retrospectively collected on 22 consecutives patients, who underwent surgery for neuroendocrine tumors of pancreas between November, 1991 and September, 2005. These data were used to set the TNM. RESULTS: After excluding 5 patients, the remaining 17 patients were analyzed. In 9 patients, with a mean age of 39 years, tumors were benign with a mean size of 1.8 cm, classed at stage I-IIa, whereas for 8 patients with a mean age of 57 years, tumors were malignant with a mean size of 6cm and were classed at stage IIb-IV. There were 3 deaths in stage IIb-IV, and none in stage I-IIa. CONCLUSION: TNM may be considered as a useful tool for prognostic stratification, but true benign tumors need to be excluded in order to improve the classification. Size and age appeared as variables affecting malignant behavior and the prognosis. PMID- 20583442 TI - Limited pancreatectomy for metastatic pancreatic tumors from renal cell carcinoma. AB - BACKGROUND/AIMS: Metastasis of renal cell carcinoma (RCC) to distant organs occurs commonly, even after radical nephrectomy, but metastatic lesions are rarely detected in the pancreas. The present study aim was to improve the postoperative quality of life of a patient with pancreatic metastasis of RCC through limited resection of the pancreas. METHODOLOGY: Since therapeutic modalities including chemotherapy or radiation are ineffective for metastatic tumors, surgical intervention is a treatment of choice in selected patients. In patients with multiple pancreatic metastases, however, near-total or total pancreatectomy may result in a lower quality of life postoperatively due to endocrine and exocrine pancreatic insufficiency. RESULTS: We used limited resection of the pancreas combined with removal of the uncinate process and distal pancreatectomy for a 65-year-old woman with multifocal pancreatic metastases located in the uncinate process, body, and tail of the pancreas, which were detected 6 years after radical nephrectomy for RCC. This surgical procedure allowed preservation of about 40% of the pancreatic parenchyma, with complete excision of metastatic tumors in the pancreas. CONCLUSIONS: The patient has had an excellent quality of life with well-preserved pancreatic function and no evidence of tumor recurrence for 31 months after pancreatic surgery. PMID- 20583441 TI - SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors. AB - BACKGROUND/AIMS: Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). METHODOLOGY: We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. RESULTS: In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. CONCLUSION: The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP. PMID- 20583443 TI - Actinomycosis of the pancreas: a case report and review of the literature. AB - Actinomycosis is a chronic suppurative and granulomatous disease usually caused by Actinomyces israelii. The pathogen produces a characteristic granulomatous inflammatory fibrosis and mass lesion. Abdominal actinomycosis is often difficult to diagnose before operation because of its rarity and chronic disease progression without any characteristic clinical features. In particular, pancreas is very rare location of actinomycosis. The present paper is a report of a case of 55-year-old man with pancreatic actinomycosis presenting as symptoms of pancreatitis. The patient was confirmed by pancreatoduodenectomy for impression of pancreatolith and mass-like lesion of head portion of pancreas. Treatment with operation followed by additional oral penicillin therapy for 3 months was successful. We report a case of pancreatic actinomycosis with a brief review of literature. PMID- 20583444 TI - Extreme analysis of risk factors for lymph node metastasis in gastric cancer. AB - BACKGROUND/AIMS: The accurate diagnosis of lymph node metastasis is necessary in gastric cancer. This study was carried out to identify the risk factors of lymph node metastasis by extreme analysis. METHODOLOGY: Data from 77 patients with lymph node-positive small gastric cancer and 128 patients with lymph node negative large gastric cancer were collected. The relationship between the two groups was compared, based on the clinical, pathologic, and preoperative clinical laboratory analysis findings. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: Rural residence, introversive personality, low third gastric cancer, low serum fibrinogen content, serosal invasion, and high serum CEA level were found to be associated with lymph node metastasis. The rural residence, introversive personality, serosal invasion, and high serum CEA level were the independent risk factors for lymph node metastasis in the multivariate logistic regression model. CONCLUSIONS: Rural residence, introversive personality, serosal invasion, and high serum CEA level were significantly and independently related to lymph node metastasis. The limited surgery with potentially incomplete lymph node dissection is not recommended in gastric cancer patients with these risk factors. PMID- 20583445 TI - Assessment of interactions between mucins of gastric juice and Helicobacter pylori--preliminary study. AB - BACKGROUND/AIMS: Helicobacter pylori resides primarily in the gastric mucus layer composed of carbohydrate-rich glycoproteins, mucins. Carbohydrates of the secretory MUC 5AC mucin are one of the proved receptors for H. pylori adhesins. A participation of the membrane-associated MUC 1 in the mechanism of infection is also suggested. The main aim of the study was to support the participation of the membrane associated MUC 1 mucin in the mechanism of infection. METHODOLOGY: 13 gastric juices were included in the study. The presence of MUC 5AC and MUC 1 mucins as well as H. pylori bindings were performed using ELISA tests. RESULTS: MUC 1 and MUC 5AC mucins were present in all the examined juices. H. pylori adhered to both glycoproteins. CONCLUSIONS: H. pylori bind to the secretory MUC 5AC mucin as well as to the epithelial MUC 1. This supports the idea that the membrane-associated mucin is involved in the mechanism of H. pylori infection. PMID- 20583446 TI - The mRNA expression of cytochrome P450 isoforms in human gastric tissue. AB - BACKGROUND/AIMS: Human Cytochrome P450 (CYP) comprises a multigene family of microsomal enzymes that metabolize a wide variety of xenobiotics, including drugs and carcinogens. Although the a number of CYP enzymes were also detected in epithelial cells along the gastrointestinal tract, little is known about the expression of CYP genes in gastric tissue. METHODOLOGY: In this study, the expression patterns of CYP isoforms was investigated in a total of 14 antral biopsy tissues obtained from the patients with either chronic gastritis (n = 6) or cancer (n = 8) by gene-specific real-time reverse transcriptase -PCR analyses. We employed primer sets specific for CYPs -1A1, -1A2, -2A6, -2B6, -2C, -2D6, 2E1, and -3A5. RESULTS: Among the isoforms CYP1A1, CYP2C and CYP2D6 gave rise to detectable mRNAs in all 14 gastric tissues while the mRNAs for the other CYPs were detected in some of the tissues. The expression patterns were compared to clinical parameters. There were no significant differences in the parameters between the two groups; however the mRNA expression of CYP2A6 was significantly higher in women than man (p < 0.05). CONCLUSIONS: Our data suggests that the CYP isoforms were independently expressed with respect to the pathological status in human gastric tissue. PMID- 20583447 TI - Gastric variceal rupture successfully treated with repeated EIS and EVL. AB - A 68-year-old female with liver cirrhosis presented at the Emergency Room of our hospital with copious tarry stools. Upper gastrointestinal endoscopy showed an isolated gastric variceal rupture, and we performed endoscopic injection sclerotherapy using cyanoacrylate, on four occasions, resulting in successful hemostasis. Injection of CA is a useful emergency treatment option for gastric variceal bleeding without gastro-renal shunt. PMID- 20583448 TI - Usefulness of laparoscope-assisted antrectomy for gastric carcinoids with hypergastrinemia. AB - The mechanisms responsible for development of gastric carcinoid tumors (type I carcinoids) in type A atrophic gastritis are hyperplasia of enterochromaffin-like cells that are associated with hypergastrinemia, and tumorigenesis. Endoscopic resection and gastrectomy are applied as treatment modalities for gastric carcinoids associated with gastrin hypersecretion. However, since the underlying pathology is the hyperplasia of gastrin-secreting cells and over-production of gastrin in the antropyloric region, antrectomy seems a logical treatment modality. To date, we have performed laparoscopic-assisted anterectomies in 3 cases of type I gastric carcinoid. The lesions have regressed or disappeared in 2 cases, in which resections of the foci were not performed. Furthermore, no has been observed in the other case, in which laparoscopic resection was performed. A laparoscopic antrectomy for type I gastric carcinoid is a minimally invasive treatment relevant to the pathology of the disease, and it is also expected to produce regression or even spontaneous resolution of the tumor. PMID- 20583449 TI - Successful treatment of a primary gastric T-cell lymphoma lacking the human T cell leukemia virus type 1. AB - Primary gastric lymphomas generally are of B-cell lineage. Among the previously reported cases of exceptional primary gastric T-cell lymphomas, most demonstrate evidence of human T-cell leukemia virus type 1 (HTLV-1) infection with a poor prognosis. The present study is a report of a rare case of primary gastric T-cell lymphoma without HTLV-1 which could be successfully treated with surgical resection and adjuvant chemotherapy. The patient was a 50-year-old Japanese male who presented with epigastric pain. Clinical examination showed no lymphadenopathy or skin changes. Radiographic and endoscopic examinations revealed an ill-demarcated ulcerative lesion in the stomach, and a biopsy specimen confirmed high-grade lymphoma. Total gastrectomy with regional lymph node dissection was performed. Histological examination of the gastric lesion revealed a malignant lymphoma, diffuse large cell type, with lymph nodal involvement. On immunohistochemistry, tumor cells were positive for CD3, CD4 and CD30, but negative for CD8, CD20 and CD56, implying a T-cell nature. Following surgery, the patient received 8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone/CHOP). To date the patient has been free of recurrence for 86 months without further treatment. Review of previously reported cases of primary gastric T-cell lymphoma indicates that the prognosis is better without than with HTLV-1. We conclude that primary gastric T-cell lymphomas without HTLV-1 should be managed in the same way as the more common diffuse large B-cell type gastric lymphomas. PMID- 20583450 TI - Does expression of receptor tyrosine kinases in gastric adenocarcinoma correlate with clinicopathological parameters? AB - BACKGROUND/AIMS: This study was initiated in order to define the (co-)expression patterns of target receptor tyrosine kinases (RTKs) in human gastric adenocarcinoma and to correlate them with clinicopathological parameters. METHODOLOGY: The (co-)expression pattern of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 was analyzed in 56 samples of human gastric adenocarcinoma and correlated with staging and survival. RESULTS: VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 were expressed at relevant levels in 79%, 50%, 50%, 63%, 55% and 30%, respectively. VEGFR2, VEGFR3, and PDGFRbeta were significantly co-expressed. Thirty-four percent of gastric adenocarcinoma samples revealed a co-expression of 6 receptors, 27% expressed 5 receptors and only 23% showed expression of 3 receptors or less. Expression of VEGFR1, VEGFR2, VEGFR3, PDGFRalpha, PDGFRbeta and EGFR1 in gastric adenocarcinoma did not significantly correlate with a higher pT-category, the presence of lymph node metastasis (pN+) or overall survival. However, a trend towards a higher pT-category was seen for expression of VEGFR1 without reaching statistical significance. CONCLUSIONS: The data obtained reveal that specific RTKs are significantly co-expressed. However, co-expression of RTKs did not impact on staging or survival. It has to be further analyzed, if the expression of the respective ligands is of higher relevance than the expression of the receptor itself. PMID- 20583451 TI - Health characteristics of the American Indian or Alaska Native adult population: United States, 2004-2008. AB - OBJECTIVE: This report compares national estimates for selected health status indicators, health behaviors, health care utilization, health conditions, immunizations, and human immunodeficiency virus (HIV) testing status for American Indian or Alaska Native (AIAN) adults with those for white, black, Asian, and Hispanic adults aged 18 years and over. METHODS: The estimates in this report were derived from the Family Core and the Sample Adult core components of the 2004-2008 National Health Interview Surveys, conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics. Estimates were generated and compared using the SUDAAN statistical package to account for the complex sample design. RESULTS: In general, compared with other groups, non Hispanic AIAN adults' are more likely to have poorer health, unmet medical needs due to cost, diabetes, trouble hearing, activity limitations, and to have experienced feelings of psychological distress in the past 30 days. Non-Hispanic AIAN adults are more likely to be current smokers and current drinkers compared with other adults. CONCLUSION: The non-Hispanic AIAN community faces many health challenges as reflected in their higher rates of risky health behaviors, poorer health status and health conditions, and lower utilization of health services. PMID- 20583452 TI - Another case of knotting of an epidural catheter. PMID- 20583453 TI - Health insurance in the United States. PMID- 20583454 TI - Achieving the opt out for Medicare physician supervision for nurse anesthetists. AB - With California's July 2009 opt-out from the Medicare physician supervision requirement for nurse anesthetists, 15 states have now opted out since 2001. The work of the American Association of Nurse Anesthetists (AANA) that led to the supervision opt-out rule being implemented has a long history. Beginning in 1994, when the Health Care Financing Administration (HCFA) first proposed deferring to the states on the supervision issue, the AANA worked for 7 years with HCFA and members of Congress to lay the groundwork for the opt-out rule that ultimately enabled the California governor's recent action. PMID- 20583455 TI - Prolonged apnea after small single dose of intravenous tramadol. AB - We report an unusual case of respiratory depression and prolonged apnea after a single, 50-mg intravenous dose of tramadol. Shortly after an uneventful surgery and anesthesia, the patient was administered intravenous tramadol. Soon after the tramadol injection, the patient became apneic, did not respond to verbal command, and started exhibiting oxygen desaturation. He was quickly administered 100% oxygen and positive pressure ventilation via a Bain circuit, and it took 45 minutes for the spontaneous respiration to return to regular. The respiratory depression could be due to increased amount of (+)enantiomer in that ampoule of tramadol. Physiological parameters affecting the metabolism of either enantiomer of tramadol or perioperative drugs need to be evaluated, as do physiological changes affecting the activity or metabolism of (+enantiomer. This case report demonstrates that even a small single dose of tramadol administered intravenously in the immediate postoperative period after general anesthesia may manifest as sudden and prolonged apnea. PMID- 20583456 TI - Effects of Celox and TraumaDEX on hemorrhage control in a porcine model. AB - The purpose of this study was to compare the effectiveness of 2 hemostatic agents, chitosan-based Celox and the biopolymeric, microporous particles TraumaDEX, with a control group in a porcine model of hemorrhage. The animals were randomly assigned to 1 of 3 groups: Celox (n = 5), TraumaDEX (n = 5), or a standard pressure dressing alone (n = 5). To simulate a battlefield injury, the investigators generated a compound groin injury with transection of the femoral artery and vein in 15 pigs. After 1 minute of uncontrolled hemorrhage, Celox or TraumaDEX was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 minutes of direct manual pressure was applied to the wound, followed by a standard pressure dressing (3M Coban). After 30 minutes, dressings were removed, and the amount of bleeding was measured. There were statistically significant differences in bleeding between Celox and control (P = .01) and between TraumaDEX and control (P = .038), but no statistically significant difference in bleeding between Celox and TraumaDEX (P = .478). Celox and TraumaDEX may be effective hemostatic agents for use in civilian and military trauma. PMID- 20583457 TI - Anesthetic management of a pituitary tumor resection with dexmedetomidine. AB - Dexmedetomidine (Precedex, Hospira, Lake Forest, Illinois), an alpha-2 agonist, mainly is used for sedating mechanically ventilated uncooperative patients in the intensive care setting. It also is being used by anesthesia providers for multiple purposes, including cardiothoracic surgeries, neurological surgeries, and awake-fiberoptic intubations and for patients with a high risk for airway obstruction. This article reports the investigation of the off-label use of dexmedetomidine as an anesthetic adjunct for a transsphenoidal pituitary tumor resection in an adult. The dexmedetomidine infusion not only provided the patient with added sedation but also decreased the need for narcotics and volatile agents while providing hemodynamic stability. PMID- 20583458 TI - Operative splenectomy for treatment of homozygous thalassemia major in Afghan children at a US military hospital. AB - Afghanistan is a war-ravaged country surrounded by mountainous terrain. Due to the geography and harsh living conditions, people have intermarried among tribes for centuries. The right familial combinations can cause manifestations of genetic linked diseases. Thalassemia major is one of these genetic diseases that are prevalent throughout southwest Asia and Africa. This condition is so severe that if left untreated, many patients die before their fifth birthday. Modern treatments in developed countries are not available in remote regions of Afghanistan. Frequent blood transfusions and surgical removal of enlarged spleens are the only options to improve life expectancy and quality of life. US military surgical hospitals and teams frequently encountered these patients and provided surgical treatment. Overall, surgical treatment of hypersplenism due to thalassemia major in this austere environment was highly successful. This article discusses the preoperative plan, intraoperative management, and postoperative care provided to 45 infants and children who underwent open splenectomy at a US military forward operating field hospital in Afghanistan. PMID- 20583459 TI - Neuraxial anesthesia for a parturient with hypogammaglobulinemia: a case report. AB - Hypogammaglobulinemia is characterized as a deficiency in humoral immunity. Humoral immunity deficiencies include the absence of B cells and/or serum immunoglobulins. Common clinical features include a predisposition toward infections naturally defended against through antibody-mediated responses. Clinical manifestations of this condition, in the parturient, may contraindicate neuraxial anesthesia. A 30-year-old parturient with hypogammaglobulinemia was admitted for repeated cesarean delivery and a bilateral tubal ligation. The pathophysiology and anesthetic management of the parturient with hypogammaglobulinemia is discussed. PMID- 20583460 TI - Ischemic optic neuropathy after spine surgery. AB - Visual loss is a traumatic occurrence that has been reported after prone spine surgical procedures performed under general anesthesia. The most common cause of postoperative visual loss is ischemic optic neuropathy. Although the incidence of postoperative visual loss is rare, this devastating injury has been reported more frequently. Several factors increase the risk for the development of ischemic optic neuropathy. Results from several case studies have attributed ischemic optic neuropathy with vision loss after general anesthesia to perioperative anemia, blood loss, hypotension, and prolonged operative times. Ischemic optic neuropathy usually presents with painless visual loss and visual field deficits during the immediate postoperative period. There is no definitive treatment. Prevention is the key. PMID- 20583461 TI - Vagal nerve stimulation: a case report. AB - Despite numerous medications designed to eliminate or decrease seizures, an estimated 20% of epileptic patients in the United States remain refractory to these agents. Vagal nerve stimulation can decrease the number of seizure episodes. In 1997, the US Food and Drug Administration approved the first implantable stimulation device for the treatment of medically refractory epilepsy. This case report describes the anesthetic management of a patient for placement of a vagal nerve stimulator. A review is presented of the current literature regarding long-term antiepileptic drug therapy and its effect on anesthetic management, pathophysiology of epilepsy and seizure propagation, and the effects of commonly used anesthetic agents on the seizure threshold. Also discussed are the physiology of vagal nerve stimulation, benefits and potential complications that may occur with its implantation, and device mechanics as it relates to future surgical procedures. As the use of vagal nerve stimulators increases, knowledge of these processes is important to ensure safe and effective anesthetic management. PMID- 20583462 TI - Anesthesia case management for thyroidectomy. AB - An intimate knowledge of the anatomy, physiology, pathophysiology, pharmacology, and specific issues related to anesthesia case management for thyroidectomy is essential to provide high-quality care. Airway management may be difficult despite a normal airway examination due to impingement of a thyroid mass on the laryngeal and tracheal structures. Anesthetists must be prepared to use emergency airway adjuncts in case a patient cannot be ventilated or intubated. Because sympathetic nervous system hyperactivity is associated with increased amounts of thyroid hormone, it is essential that all patients having an elective thyroidectomy be in a euthyroid state before surgery. There are multiple preoperative antithyroid medication regimens that effectively treat thyroid hormone hypersecretion. However, although a rare event, thyroid storm can still occur during the perioperative period. Anesthetic considerations and surgical complications are presented. PMID- 20583463 TI - [Microencapculation of daunorubicin with biodegradable polymer matrix]. AB - Procedure for microencapsulation providing stable formation of high quality microspheres was designed. Conditions for deposition of the anthracycline antibiotic daunorubicin to polymer matrix were developed and microsheres loaded with various quantities of the drug were prepared. The kinetics of the in vitro and in vivo release of daunorubicin from the microsheres was studied. The rate of the rubomycin release to the medium in vitro (balanced phosphate buffer at 37.8 degrees C) in a 300-hour experiment directly depended on the quantity of the incorporated drug and averaged 0.81 x 10(-4) to 2.3 x 10(-4) mcg/ml x h. The experiment on laboratory animals with intraperitoneal administration of the rubomycin microsperes showed that the drug remained in the blood and abdominal liquid for a long time (up to 10 days). Possible control of the quantity of the rubomycin encapsulation to the polymer matrix, no sharp efflux of the drug at the early stages of the observation and low rate of the drug release to the medium allowed to conclude that the use of the biodegradable polymer microsperes as carriers of the high toxic antibiotic providing its prolonged action was prospective. PMID- 20583464 TI - [Red blood cells hemolysis under combined action of ultrasonic waves and polyene antibiotics]. AB - Ultrasonic and induced hemolysis of red blood cells in the presence of alkyl derivatives of amphotericin B and levorin modified by the amino and carboxy groups was investigated. Amphotericin B derivatives such as metamphocin, ethamphocin and carboamphocin and levorin derivatives such as levoridon, isolevoridon and carbolevoridon were shown to have their own hemolytic activity in isotonic medium at concentrations of 10(-5) - 10(-4) M in erythrocyte suspension. The exposure of erythromycytes to pure dimethylsulfoxide (0.1-30%), the main solvent of polyene antibiotics, as well as to propamphocin and butamphocin did not induce hemolysis and had a stabilizing action an red blood cells during the ultrasonic hemolysis. It was suggested that changing of the mechanical strength of erythrocytes under the action of the polyenes was likely associated with impairment of microviscosity of the protein-lipid system of the erythrocyte membranes due to formation of structural ionic channels of molecular size. PMID- 20583465 TI - [Express determination of beta-lactam antibiotics in biological matter with potentiometric sensors]. AB - Stability of aqueous solutions of beta-lactam antibiotics (sodium benzylpenicillin, oxacillin, amoxycillin, phenoxymethylpenicillin, cefotaxime, cefazolin) in biological matter of various acidity was investigated spectrophotometrically. Potentiometric sensors (based on ionic association of beta-lactam tetradecylammonium) sensitive to penicillins and cephalosporins within the concentrations of 1 x 10(-5) - 1 x 10(-1) M were designed. The sensors provided determination of concentration of individual antibiotics and their summary content in the presence of a significant excess of inorganic ions. Express methods for ionometric determination of beta-lactams in blood serum and mixed saliva were developed. PMID- 20583466 TI - [Study on activity of antistaphylococcal antibiotic batumin against methicillin resistant strains of staphylococci]. AB - A stable increase in the frequency of methicillin resistant clinical isolates of staphylococci was recorded. 258 strains of Staphylococcus aureus and S. epidermidis, including methicillin resistant ones, were susceptible to batumin. The minimum inhibitory concentration of batumin ranged within 0.04 and 0.5 mcg/ml and depended on the concentration of the microbial cells and the medium pH. The medium composition had limited influence on the batumin activity. No differences in the batumin activity against methicillin susceptible and methicillin resistant staphylococci were observed. The antibiotic had bactericidal action on the strains (2-4 mcg / ml). The results of the study showed that batumin ointment was prospective for eradication of S. aureus. including MRSA, in cases with the nasal carriage and for control of multiresistant strains during hospital outbreaks. PMID- 20583467 TI - [Efficacy of cefixime and cefepime vs. other cephalosporins in experimental plague of albino mice due to variants FI+ and FI- of the plague microbe]. AB - Efficacy of cefixime and cefepime vs. ceftriaxone, cefotaxime, ceftazidime and cefoperazone was studied in vitro and in the treatment of experimental plague of albino mice due to natural, antigen complete strains of the plague microbe and the pathogen variants deprived of the ability to produce the capsule antigen fraction I (FI- phenotype). The MICs of cefixime and cefepime for 20 FI+ and 20 FI- strains of the plague microbe were 0.02-0.08 mg/l, that corresponded to the MICs of ceftriaxone, cefotaxime and ceftazidime. The MICs of cefoperazone were somewhat higher (0.1-0.2 mg/l). The ED50 values of cefixime and cefepime for prevention and treatment of experimental plague in mice statistically did not significantly differ from the ED50 values of ceftriaxone, cefotaxime, ceftazidime and cefoperazone. The efficacy indices (EIs) of cefixime and cefepime were > 10(4) independent of the infective strain phenotype (FI+ or FI-) and did not differ from those of ceftriaxone and ceftazidime. The efficacy of cefotaxime and cefoperazone was somewhat lower (EIs 1.7 x 10(3)-8.9 x 10(3)). Both the antibacterials were shown to provide high protective and therapeutic efficacy (80 100% of the survivors) independent of the phenotype (FI+ or FI-) of the pathogen infective strain. The results allowed to consider the antibiotics prospective in prevention and treatment of plague. PMID- 20583468 TI - [Treatment of late stages of anthracic infection]. AB - Ways for increasing the anthrax treatment efficacy by combined use of antibiotics, toxin neutralizing, immunomodulating, symptomatic and pathogenetic agents are considered. The dynamics of the infection development was studied on rabbits by the microbiological, cytochemical, biochemical and cytomorphologic criteria. The efficacy of monoantibacterial and complex schemes of the etiopathogenetic therapy of the disease at the early and late stages (phases) of the infection generalization was estimated. PMID- 20583469 TI - [Problem of antibiotic resistance development in Staphylococcus epidermidis population subject to technogenic load]. AB - Antibiotic resistance of Staphylococcus epidermidis isolates from the pharynx of persons in various regions of Krasnoyarsk was tested. The highest percentage of the isolates was resistant to beta-lactam antibiotics in both the ecologically comparatively favourable regions and the regions exposed to diverse technogenic loads. However, the isolates from the ecologically unfavourable regions were highly resistant to a greater variety of antibiotics. The neuronet analysis as well revealed high informative value of the results. PMID- 20583470 TI - [Panavir, as a broad spectrum antiviral agent]. PMID- 20583471 TI - [Pilot plant for microbiological synthesis. Engineer and technological aspects]. AB - A biotechnological pilot plant (National Research Centre of Antibiotics) and its technical potentialities in production of various biosynthetic products are described. Some engineer and technological aspects of the fermentation equipment and particularly sterilization of the media and apparatus, fermentation broth aeration under sterile conditions and control of biosynthesis technological parameters (t degrees, pO2, P, pH, foaming, etc.) are considered. The pilot plant is designed for fermentation processes under aseptic conditions with the use practically of any object, from bacteria to tissue cultures. PMID- 20583472 TI - K-ras expression--marker of dysplasia and cancer. AB - Molecular and epidemiological data indicated that the presence of HPV virus is not sufficient to induce transformation, suggesting the implication of other several cellular factors. Constitutive activation of the Ras signaling pathway is an important component of malignant progression for a number of different cancers. In this context, the objectives of our study were: the quantitative assessment of the K-ras gene expression changes in the development of the HPV positive cervical cancers. We observed that the K-ras mRNA expression levels did not gradually increase with the severity of injury. The mRNA expression in the ASCUS increased 2.02 times as compared with the control group, while in LSIL group only 1.76 times. However ras expression was increased in the HSIL/cancer group by 2.27 times when was reported to the control group. The presence of low risk HPV infection (IrHPV) does not lead to increased ras expression, remaining at baseline, but K-ras expression was increased in the presence of high risk HPV infection (hrHPV). In addition, we noted that in hrHPV single infections ras expression is increased (0.96 +/- 0.48) comparing with hrHPV co-infections. Our findings indicate that high expression of ras among hrHPV infection can be a marker of cervical cancer development. PMID- 20583473 TI - Curdlan derivatives able to enhance cytostatic drugs activity on tumor cells. AB - The chemotherapy success to kill cancer cells depends on its ability to stop cell division. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. Taking into account the severe side effects of chemotherapy, drugs producers also focus on natural products obtained either from medicinal plants, or from microorganisms. The complex polysaccharides named beta-glucans are active compounds with immune activity. beta-glucan polymers belong to a class of drugs with effects on the immune system, such as: anti-tumoral, anti-infectious, protection against fungi, bacteria and viruses infections. The correct selection of beta-glucans is essential to identify compounds with favorable clinical effects. The aim of this study was to investigate the capacity of six Curdlan (beta-glucan) derivatives to up-regulate the Doxorubicin, Actinomycin D and Cyclophophamide cytostatic drug activity on tumor cells (murine B16 melanoma and human HEp-2 laryngeal carcinoma cell lines). Our results demonstrated that Palm SP derivative, as well as SP and Palm CM/SP derivatives were able to potentiate Doxorubicin action or Actinomycin D effect on B16 tumor cells. SP derivative significantly enhanced cytostatic activity of Cyclophosphamide on B16 cells. All the investigated Curdlan derivatives (SP, Palm CM/SP, CM/SP, Palm CM, Palm SP and CM) were able to inhibit HEp-2 tumor cell growth, by up-regulating Doxorubicin and Actinomycin D cytostatic activity. PMID- 20583474 TI - The influence of some probiotic supernatants on the growth and virulence features expression of several selected enteroaggregative E. coli clinical strains. AB - The purpose of this study was the assessment of the influence of three probiotic supernatants (Bifidobacterium breve ATCC 15700, Enterococcus faecium ATCC 19434, Lactobacillus casei subsp. casei ATCC 393) on the growth (quantified by viable cell counts) and virulence features expression (adherence ability to HEp-2 cells and inert substratum- slime test) of several selected EAggEC diarrhoeagenic strains as well as the cytotoxicity of the respective supernatants on HEp-2 cells. RESULTS: Our in vitro studies are demonstrating that the selected supernatants, when added simultaneously with the bacterial culture are generally opposing to the adherence to the cellular substratum by the EAggEC strains. When added after the pre-adherence period, the supernatants did not change the adherence indexes of the EAggEC strains, but induced slight changes in the adherence pattern, reducing the frequency and size of bacterial aggregates. Only in few cases, the bacterial growth rate was slightly increased or sustained by the probiotic supernatants, a possible explanation being that we used supernatants obtained from 24 hrs fresh cultures, which are probably still containing some nutrients and probably also other growth factors. CONCLUSION: Our results are demonstrating that soluble probiotic metabolites accumulated in culture supernatants may interfere with the first step of adherence and colonization of the cellular and inert substrata by EAggEC strains, probablyby the cross-talk between probiotic soluble molecules and quorum-sensing mediators of opportunistic strains; so, direct contact between the probiotic and pathogenic bacteria are not always necessary for the occurrence of a protective effect, that could be partly mediated by the soluble molecules secreted by specific probiotic strains. PMID- 20583475 TI - In vitro study of the inhibitory activity of usnic acid on dental plaque biofilm. AB - The vegetal extracts are used as an ecological alternative to classical anti infectious treatments based on antibiotics, exhibiting the advantage of reduced secondary effects. Most of these compounds are secondary metabolites, especially aromatic substances synthesized by plants in a reduced concentration. The aim of this study was to investigate the influence of usnic acid against quorum sensing and response mechanisms involved in the initiation and development of the dental plaque biofilm and its tolerance to antimicrobials. Three samples of super gingival dental plaque were treated for different time intervals with usnic acid at 200 ig/ml in dimethyl-sulfoxide, representing the MIC value. Each dental plaque sample was inoculated in Brain Heart Infusion medium to establish the microbial growing curve by viable cells counts using the tenfold microdilutions method. For strains identification there were used the microtest galleries: API 20Strep, API Staph, API 20NE, API 20E. MIC value for usnic acid was determined by twofold microdilution technique. Usnic acid selectively inhibited the biofilm development by Gram positive bacteria and the expression of haemolytic properties of strains isolated from the dental plaque. The growth curve of the isolated strains was affected by usnic acid, the changes consisting of the lag phase extension to 6-10 h (this time interval being considered as the persistence time of antimicrobial activity) and the significant decrease of the viable cell number and consecutively, the prolongation of the generation time. These effects are demonstrating the interference of the usnic acid with the intra- and interspecies signalling mechanisms based on quorum sensing and response and dependent on cell density, giving the possibility to use them as an active principle in some new pharmaceutical formula intended for the prevention and treatment of gingival and periodontal pathologies. PMID- 20583476 TI - In vitro susceptibility of Erwinia amylovora (Burrill) Winslow et. al. to Citrus maxima essential oil. AB - Regulatory constraints and environmental and human health concerns have promoted the search for alternative bio-control strategies of fire blight, a destructive disease of rosaceous plants which produces serious losses in apple and pear orchards all over the world. The aim of this study was to establish the antimicrobial activity of Citrus maxima essential oil against Erwinia amylovora. An agar diffusion method was used for the screening of the inhibitory effect of Citrus maxima essential oil on bacterial strains growth. The quantitative inhibitory effect of pomelo oil on in vitro biofilm development was established by a microtiter colorimetric assay. In order to investigate the ability of pomelo oil to interfere with bacterial adherence and subsequent biofilm development on leaves obtained from different pomaceous fruit trees species and cultivars: Pyrus (Napoca, Williams), Malus (Golden Delicious) and Cydonia (Aromate), leaves were immersed in pomelo oil for 1, 2, 3, 5 and 10 minutes before exposing them to bacterial colonization. The architecture of bacterial biofilms developed on leaf surface was analyzed using Confocal Scanning Laser Microscopy (CSLM). Our results showed that Citrus maxima essential oil inhibited the development of bacterial biofilms on leaves, pomelo oil being more active on Cydonia (Aromate) leaves when the leaves were treated for 5 minutes. The results obtained from this study may contribute to the development of new bio-control agents as alternative strategies to protect fruit trees from fire blight disease. PMID- 20583477 TI - Antibiotic resistance of Gram negative bacilli strains isolated from the Intensive Care Unit in Fundeni Clinical Institute, Bucharest, Romania. AB - The aim of this study was to investigate the antibiotic resistance profile of 58 Gram negative bacilli strains (GNB): 36 non-fermentative GNB (NGNB), including 19 strains of Acinetobacter spp., 11 of Pseudomonas aeruginosa, 6 of Stenotrophomonas maltophilia and 22 enterobacterial strains (14 strains of KEHSs, 6 belonging to the group Proteus-Providencia and 2 Escherichia coli) isolated from nasal, pharyngeal exudates and also from bronchial secretions, from immuno depressed patients admitted in the Intensive Care Unit of Fundeni Clinical Institute. METHHODS: the antibiotic susceptibility testing was performed according to CLSI 2009 recommendations and the production of beta-lactamases was investigated by ESBL chromogenic media, double disc diffusion test, ESBL E-test, Amp C E-test and MBL E-test. RESULTS: 68% of the enterobacterial strains produced extended-spectrum beta- lactamases (ESBL), 13.63% of them expressing simultaneously the Amp C enzyme. All enterobacterial strains were susceptible to carbapenems (Imipenem and Ertapenem). Metallo-beta lactamases production among NGNB strains with resistance to Imipenem was high (80%), these strains being also multi-resistant to the majority of tested antibiotics with the exception of colistin. CONCLUSIONS: our results showed that the majority of the analyzed strains were multi-drug resistant. Antibiotic multi-resistance and the increasing number of severe infections caused by these strains are a major issue for ICU, where patients with severe diseases and destabilized physiological condition are often admitted. PMID- 20583478 TI - Group B streptococcus colonization of Romanian women: phenotypic traits of isolates from vaginal swabs. AB - In the attempt to enrich the local contemporary laboratory data regarding the group B streptococcus (GBS) colonization, isolates obtained from the vaginal swab cultures were characterized for their serotype distribution and antibiotic susceptibility. The 100 GBS isolates analyzed were collected during a four-month period of year 2009 from women screened in ambulatory for vaginal carriage of GBS. The GBS isolates were classified based on their capsular polysaccharide structures using commercially available antisera. Susceptibility to penicillin, ampicillin, erithromycin, clindamycin, tetracycline, ofloxacin, and chloramphenicol was initially tested using antibiotic disk diffusion technique according to CLSI guidelines. Minimum inhibitory concentrations of erythromycin and tetracycline for the isolates with reduced susceptibility were evaluated according to the CLSI criteria and macrolide-lincosamide-streptogramin B (MLSB) resistance was investigated by a double-disk test with erythromycin and clindamycin disks. All the GBS isolates were serotypeable. Their distribution comprised six different serotypes of which serotypes II (26%), III (26%), and Ia (19%) prevailed and no serotype VI, VII, and VIII isolates were found. Overall, the GBS isolates were fully susceptible to penicillin and ampicillin, but the rates of susceptibility to the other antimicrobial agents tested were decreased, ranging from 87% for chloramphenicol to 5% for tetracycline. Reduced susceptibility to clindamycin and erythromycin was detected in 18% and 19% of isolates, respectively. For the latter, 84% displayed a constitutive MLSB phenotype, 11% had an inducible MLSB phenotype, and M phenotype was expressed by 5% of them. Erythromycin-resistant GBS isolates displayed concurrently resistance to at least one more antibiotic. In conclusion, according to our study the most frequent GBS serotypes isolated from the vaginal microflora were II and III, followed by serotype Ia. While the GBS isolates remain susceptible to beta lactams, resistance to alternative antimicrobial drugs such as erythromycin and clindamycin seems to be an increasing concern for our region. Further phenotypic and genotypic studies are required to identify specific aspects of GBS strains colonizing or infecting the local population. PMID- 20583480 TI - Cost-cutting in high demand. PMID- 20583479 TI - Investigation of Helicobacter pylori infection in Jordanian patients using six enzyme immunoassays for immunoglobulin G (IGG) and IGA testing. AB - Helicobacter pylori (H. pylori) is the etiologic agent of a variety of gastrointestinal disorders. The rationale of the current study is to evaluate six enzyme immunoassays for detection of anti-H. pylori immunoglobulin G (IgG) and IgA in Jordanian patients. Biopsy specimens and blood samples were obtained from patients underwent the endoscopy unit at Al-Bashir hospital in Jordan. The serum samples were investigated for the presence of anti-H. pylori IgG and IgA antibodies in patients with positive H. pylori biopsy samples. The results showed that IgG utilizing kits are more sensitive than of IgA kits and the IgA kits are more specific than of that IgG kits. Moreover, the biopsy is seemingly the gold standard for diagnosis of H. pylori is followed by H. pylori culture on brucella agar medium. An imperfect relation between the presence of H. pylori infection and the antibody response was existed that could be explained either because of the unsatisfactory sensitivities and specificities of the commercial kits used or because of weak immunological response in our patients to H. pylori antigens. Collectively, the H. pylori diagnosis that depends on the detection of anti-H. pylori antibodies in the hospital setting and in the screening programs should consider another test for confirmation the initial diagnosis. PMID- 20583481 TI - Spine product pricing presents latest cost control challenge. PMID- 20583482 TI - Good news: knee implant prices slip. PMID- 20583484 TI - It is not fair! PMID- 20583483 TI - Radiographs need improvement. PMID- 20583486 TI - Dishing the dirt on Facebook. PMID- 20583485 TI - Are 'working interviews' a good idea? PMID- 20583487 TI - Top tips for staying out of peer review. PMID- 20583488 TI - Sales skills for young dentists. PMID- 20583489 TI - Insurance limitations: why? PMID- 20583491 TI - A new dentist's most-asked legal questions. PMID- 20583490 TI - After dental school: now what? Sizing up your opportunities. PMID- 20583492 TI - Our country is debating where we are in relation to where we began over two hundred years ago. PMID- 20583493 TI - Diagnostic discussion. Odontogenic keratocyst. PMID- 20583494 TI - How to treat a difficult-to-anesthetize patient. Twelve alternatives to the traditional inferior alveolar nerve block. AB - In the case of the difficult-to-anesthetize patient, the inferior alveolar nerve can be particularly challenging In those patients, other approaches may be necessary to achieve profound anesthesia. This article presents techniques that may be used in those efforts. The clinician can change his target slightly, or increase the dosage of anesthetic. Accessory innervation by lingual and mylohyoid nerves sometimes needs to be addressed. Some standard alternative approaches are Gow-Gates and Varizani-Akinosi injections. Intraosseous and intraligamentary injections should be considered. For lower anteriors, infiltration and incisive nerve blocks can be effective. Slight changes in armamentarium, such as increasing the needle gauge, can be helpful. Twelve approaches that can be used instead of or as an adjunct to, the traditional Halstead injection are described. PMID- 20583495 TI - How to manage odontogenic infections. PMID- 20583497 TI - How to create accurate bite records: improving restorative predictability. PMID- 20583496 TI - How to work with the best possible staff. PMID- 20583498 TI - How to launch your dental website. PMID- 20583499 TI - Integrating child dental care at Community Smiles: the director's goals fulfilled.... AB - Community Smiles/Dade County Dental Research Clinic provides dental care to the indigent population of Miami-Dade County. A local board of directors governs the organization, with dental procedures performed by volunteer professionals from the community. The research clinic partners with community organizations to obtain sustained funding from diverse sources. The clinic has a long-term commitment to the growth and development of children in the community. Certainly, changing the structure and focus of the clinic toward children's dental care and seeking community funding and resources to institute this program was an experiment. In his four years as clinic director and chief executive officer (CEO) at Community Smiles, the late Dr. Robert M. Wolf brought increased clinic productivity and organizational change that expanded community involvement. Dr. Wolf's tenure at Community Smiles brought general increases in patients care in terms of patients visits, new patients and number of procedures performed. However, the key to his administration as clinic director and CEO was the production and integration of a children's dentistry program into the mainstream activities of the clinic. Furthermore, he oversaw the successful corporate reorganization of Community Smiles as the clinic emerged under a non-profit corporate structure employing multi-faceted community resources. Emphasizing new dental programs for children in the community is culturally and socially competent--positively impacting the public health. Community Smiles became a venue where disparities were largely eliminated and access to dental treatment increased. Health care was promoted as Community Smiles became a place that helped build a healthier community. PMID- 20583501 TI - Mapping oral health worldwide. Interview by Lois K Cohen. PMID- 20583500 TI - A response to "Dental implications of acute stroke therapy and anticoagulation for stroke prevention". PMID- 20583502 TI - The dawn of the industrial age and the cottage industry of dentistry. PMID- 20583503 TI - Chlorhexidine as a canal irrigant: a review. AB - The use of an irrigant during root canal therapy is an important factor in the cleaning and disinfecting of the root canal system. While sodium hypochlorite has been used for decades as a primary irrigant, other irrigants have been investigated as alternatives. This article reviews chlorhexidine as a canal irrigant, explores its different properties, and provides the dental practitioner with information to help make a more informed decision when choosing an irrigant. PMID- 20583504 TI - Surgical considerations and management of patients with mucocutaneous disorders. AB - Surgeons may be confronted with providing periodontal plastic or implant therapy for patients with gingival manifestations of systemic conditions. These conditions (often referred to as mucocutaneous disorders) commonly present with features of desquamative gingivitis, which was once believed to represent a disease entity. However, today, the term desquamative gingivitis is used to describe clinical features of various local or systemic diseases or disorders that result in chronic gingival lesions characterized by epithelial desquamation, erythema, ulceration, and/or vesiculobullous lesions of the gingiva. Often, other oral tissues also are involved. Mucocutaneous disorders include such disease entities as lichen planus, graft-versus-host disease, pemphigoid, pemphigus vulgaris, lupus erythematosus, erythema multiforme, and linear IgA disease. Surgeons should be able to recognize these disorders and have the tools necessary to treat these conditions so that they can render the appropriate surgical care. This article describes the diagnosis, etiology, and clinical manifestation of these disease entities, as well as the surgical considerations and management in providing care to these patients. PMID- 20583505 TI - A classification system of patients for esthetic fixed implant-supported prostheses in the edentulous maxilla. AB - Edentulous maxillary fixed rehabilitation using dental implants is challenging and requires meticulous planning because of anatomic variations and the importance of facial and dental esthetics. This article reviews the application of facial esthetics, lip support, smile lines, residual ridge position, tooth proportions, and tooth positions for different types of patients. Based on these parameters, a simple new classification system is proposed to classify patients into four categories, which will help facilitate an easier diagnostic and communicative system. It will also enable the clinician to understand when and why gingiva-colored prosthetic material is needed. Using this classification system, a stepwise method of diagnosis and management techniques are described in detail for each of the four classes. The proposed classification system has been based on an analysis of various successfully treated patients with a minimum follow-up period of 2 years. PMID- 20583506 TI - In complex restorative cases, understanding the patient's expectations is the first step. PMID- 20583507 TI - The maturation of CAD/CAM. PMID- 20583508 TI - Honor, duty, and purpose in surgery. PMID- 20583509 TI - Gold Medal Forum Winner. Unfractionated heparin three times a day versus enoxaparin in the prevention of deep vein thrombosis in trauma patients. AB - Venous thromboembolic disease is a significant source of morbidity and mortality in hospitalized trauma patients. Multiple drugs and dosing regimens have been suggested for pharmacoprophylaxis. In this study, we compared efficacy, complications, and cost of unfractionated heparin administered subcutaneously three times a day with standard-dosed enoxaparin for prophylaxis of deep venous thrombosis (DVT) in adult trauma patients over 1 year. Patients admitted for greater than 72 hours who received pharmacoprophylaxis as part of a comprehensive DVT protocol were included. A change was made in the protocol from enoxaparin (30 mg twice a day or 40 mg per day) to heparin (5000 U three times a day) at midyear. Surveillance lower extremity venous ultrasound was performed according to established institutional guidelines. Data, including demographics, associated injuries, complications, and cost, were collected and analyzed. Four hundred seventy-six patients met inclusion criteria. Two hundred thirty-seven (49.8%) patients received enoxaparin and 239 (50.2%) received heparin. Proximal lower extremity DVTs were detected in 16 (6.75%) patients in the enoxaparin group and 17 (7.11%) in the heparin group (P = 0.999). Risk factors for DVT in these patients included spinal cord injury (P = 0.001) and closed head injury (P = 0.031). There was no difference between the incidence of pulmonary emboli and bleeding. There was an estimated yearly pharmacy cost savings of $135,606. In trauma patients, subcutaneous heparin dosed three times a day may be as effective as standard-dosed enoxaparin for prophylaxis of venous thromboembolism without increased complications. Heparin three times a day for venous thromboembolism prophylaxis was associated with significant pharmaceutical cost savings. PMID- 20583510 TI - Optimizing surgical care: a contemporary assessment of temperature, oxygen, and glucose. AB - Factors such as temperature, oxygen, and glucose have recently been implicated in the development of surgical sepsis by either promoting or attenuating protective components of the innate immune response. Reducing infective sequelae and the improvement of the quality of care of surgical patients is a top practice priority today. These factors and their associated effects are discussed through the examination of recent clinical and scientific studies to provide an up-to date evidence-based review. PMID- 20583511 TI - Operative experience in the era of duty hour restrictions: is broad-based general surgery training coming to an end? AB - Since the institution of Accreditation Council for Graduate Medical Education (ACGME) resident work hour restrictions, conflicting evidence exists regarding the impact on resident case volume with most data from single-institution studies. We examined the effect of restrictions on national resident operative experience. After permission from the ACGME, we reviewed the publicly available national resident case log data (1999 through 2008) maintained on the ACGME web site (www.acgme.org), including total major cases with subanalysis of the ACGME specified categories. The mean cases per resident were compared before (1999 to 2003) and after (2003 to 2008) restrictions. After the implementation of duty hour restrictions, the mean number of total cases per resident significantly decreased (949 +/- 18 vs 911 +/- 14, P = 0.004). Subanalysis showed a significant increase in alimentary tract (217 +/- 7 vs 229 +/- 3, P = 0.004), skin/soft tissue (31 +/- 3 vs 36 +/- 1, P = 0.01), and endocrine (26 +/- 2 vs 31 +/- 2, P = 0.006) cases. However, we observed a significant decrease in head and neck (21 +/ 0.3 vs 20 +/- 0.3, P = 0.01), vascular (164 +/- 29 vs 126 +/- 5, P = 0.01), pediatric (41 +/- 1 vs 37 +/- 2, P = 0.006), genitourinary (10 +/- 2 vs 7 +/- 1, P = 0.004), gynecologic surgery (5 +/- 1 vs 3 +/- 0.6, P = 0.002), plastics (16 +/- 0.3 vs 15 +/- 0.7, P = 0.03), and endoscopy (91 +/- 3 vs 82 +/- 2, P < 0.001) procedures. Analysis of the ACGME-compiled national data confirms that duty hour restrictions have significantly impacted resident operative experience. Importantly, experience in specialty areas, including vascular and endoscopy, appears to have been sacrificed for consolidation of resources into general surgery services as indicated by the increase in alimentary tract and endocrine cases. These findings raise the following question: Is the era of truly broad based general surgery training coming to an end? PMID- 20583512 TI - Design, development, and validation of a take-home simulator for fundamental laparoscopic skills: using Nintendo Wii for surgical training. AB - Assuring quality surgical trainees within the confines of reduced work hours mandates reassessment of educational paradigms. Surgical simulators have been shown to be effective in teaching surgical residents, but their use is limited by cost and time constraints. The Nintendo Wii gaming console is inexpensive and allows natural hand movements similar to those performed in laparoscopy to guide game play. We hypothesize that surgical skills can be improved through take-home simulators adapted from affordable off-the-shelf gaming consoles. A total of 21 surgical residents participated in a prospective, controlled study. An experimental group of 14 surgical residents was assigned to play Marble Mania on the Nintendo Wii using a unique physical controller that interfaces with the WiiMote controller followed by a simulated electrocautery task. Seven residents assigned to the control group performed the electrocautery task without playing the game first. When compared with the control group, the experimental group performed the task with fewer errors and superior movement proficiency (P < 0.05). The experimental group demonstrated increased ambidexterity with improvement in proficiency of the nondominant hand over time. In conclusion, the Nintendo Wii gaming device along with Marble Mania serves as an effective take home surgical simulator. PMID- 20583513 TI - Optimization of donor management goals yields increased organ use. AB - Multiple strategies have been used in an effort to increase the pool of organs for transplantation. Standardizing donor management has produced promising results. Donor management goals (DMGs) are now being used as end points of intensive care unit care during the prerecovery phase but no prospective results have been reported. Data from the United Network for Organ Sharing Region 11 were collected for successful achievement of eight common donor management goals (mean airway pressure [MAP], central venous pressure [CVP], pH, PaO2, sodium, glucose, single pressor use, and urine output) before organ recovery. Two time periods were studied with different panels of DMGs. The analysis identified the success rate of transplantation. Goals were stratified by their statistical correlation with the number of organs transplanted per donor (OTPD) in an effort to identify the most important parameter(s). Eight hundred five organ donors were studied with 2685 organs transplanted. DMGs were assessed through two phases of the study. Achieving DMGs rose from 18 to 66 per cent associated with significant improvement in OTPD (range, 2.96 to 3.45). The success of transplantation was primarily associated with limitations in vasopressor use and PaO2. Tight glucose control did affect the rate of pancreatic transplants. Thoracic organs were the most sensitive to DMGs with a 10- to 15-fold increase in lung transplantation when PaO2 rose above 100 mmHg. MAP, CVP, pH, sodium, and urine output had little effect on transplantation. Standardization of end points of donor management was associated with increased rates of transplantation. Surprisingly, not all standard goals are necessary for optimal organ use. The most significant parameters were the low use of vasopressor agents and oxygenation. Donor management strategies should strive to optimize these goals. PMID- 20583514 TI - Flexion-extension cervical spine plain films compared with MRI in the diagnosis of ligamentous injury. AB - The purpose of this study was to compare flexion-extension (FE) plain films with MRI as the gold standard in the diagnosis of ligamentous injury (LI) of the cervical spine after trauma. A retrospective review of patients sustaining blunt trauma from January 2000 to December 2008 (n = 22929) who had both FE and MRI of the cervical spine was performed. Two hundred seventy-one patients had 303 FE films. Forty-nine also had MRI. The average Injury Severity Score was 15.6 +/- 10.2, Glasgow Coma Scale was 13.8 +/- 3.5, lactate 2.2 +/- 1.7 mmol/L, and hospital stay of 8 +/- 11.2 days. FE failed to identify all eight LIs seen on MRI. FE film sensitivity was 0 per cent (zero of eight), specificity 98 per cent (40 of 41), positive predictive value 0 per cent (zero of one), and negative predictive value 83 per cent (40 of 48). Although classified as negative for purposes of analysis, FE was incomplete 20.5 per cent (62 of 303) and ambiguous 9.2 per cent (28 of 303) of the time. The charge of FE is $535 so $48150 (90 incomplete/ambiguous films) could have been saved by eliminating these films. FE should no longer be used to diagnose LI. Given the rare incidence of these injuries, MRI should be used when there is high clinical suspicion of injury. PMID- 20583515 TI - Real-world experience with type I endoleaks after endovascular repair of the thoracic aorta. AB - Endoleaks are a frequent complication of thoracic endovascular aortic repair (TEVAR) and will likely increase in incidence with application of the technique to more complicated aortic anatomy and a wider range of thoracic aortic pathologies. Management generally consists of aggressive repair of Type I endoleaks; however, the natural history of Type I endoleaks after TEVAR remains largely unknown. The purpose of this study was to examine the incidence and characteristics of Type I endoleaks and to evaluate clinical outcomes of patients with Type I endoleaks after TEVAR. A single-center retrospective review was performed on all patients who underwent TEVAR over a 4-year period. Type I endoleaks were detected in 21 per cent (27 of 129) of patients on post-deployment aortography or CT angiography. During a mean follow-up of 750.63 +/- 483 days, 59 per cent (16 of 27) closed spontaneously; 30 per cent (eight of 27) required secondary endovascular intervention; and 11 per cent (three of 27) have persisted with no increase in maximum aortic diameter. No patients have died or required open surgical conversion as a result of their Type I endoleak. Although accurate predictors of spontaneous resolution of Type I endoleaks have yet to be definitively characterized, our initial results suggest that it may be safe to observe small Type I endoleaks given that a large percentage resolve spontaneously and no endoleak-related deaths have occurred. PMID- 20583516 TI - Differences in presentation and perioperative outcome after pancreaticoduodenectomy for cancer and benign pancreatitis. AB - The aim of this study was to examine differences in presentation and outcome in pancreaticoduodenectomy for benign and malignant processes. Pancreaticoduodenectomies performed for pancreatic adenocarcinoma or chronic pancreatitis from 2000 to 2008 were identified from a prospectively maintained database and compared. Pancreaticoduodenectomy revealed adenocarcinoma in 220 patients and benign chronic pancreatitis in 40 patients. Patients with adenocarcinoma were older (64 +/- 10.6 years and 47.6 +/- 10.8 years, respectively, P < 0.001) and more likely to demonstrate jaundice (92 and 13%, respectively, P < 0.001), weight loss (76 and 58%, respectively, P = 0.01), and discrete masses (72 and 55%, respectively, P = 0.03). By contrast, chronic pancreatitis presented with increased pain (98 and 49%, respectively, P < 0.001) and nausea (68 and 32%, respectively, P < 0.001). Patients with pancreatitis experienced reduced blood loss (227 +/- 156 and 571 +/- 626 mL, respectively, P = 0.05) and transfusion (10 and 42%, respectively, P < 0.001). Postoperatively, the groups were similar in risk of fistula, gastroparesis, overall morbidity, and mortality. Infection rates were higher in adenocarcinoma (42 and 20%, respectively, P = 0.01). Forty-nine patients underwent pancreaticoduodenectomy for presumptive chronic pancreatitis, of which nine had adenocarcinoma; logistic regression identified increasing age and jaundice as predictors of malignancy. Compared with patients with adenocarcinoma, those who undergo pancreaticoduodenectomy for chronic pancreatitis are less likely to require preoperative biliary drainage and perioperative transfusion. Infectious complication risk is higher in patients with adenocarcinoma. Increased age and jaundice should raise suspicion of cancer in patients with chronic pancreatitis undergoing evaluation for surgical treatment. PMID- 20583517 TI - Role of growth factors in improved skin flap viability caused by phosphodiesterase-5 inhibitor. AB - Flap necrosis is one of the major complications of reconstructive surgery and sildenafil citrate has been shown to decrease flap necrosis in preclinical animal models. However, the mechanisms underlying sildenafil's therapeutic efficacy are not known. As with other phosphodiesterase 5 selective inhibitors, sildenafil causes vasodilation and enhanced blood flow. In addition, sildenafil can also alter gene expression. This study is designed to test the hypothesis that increased expression of angiogenic growth factors may be responsible for therapeutic efficacy of sildenafil. A modified McFarlane flap measuring 3 x 10 cm was created on the dorsal skin of male Sprague-Dawley rats. For growth factor expression experiment, rats were administered either vehicle or sildenafil 10 mg/Kg intraperitoneal (IP). Ribonucleic acid (RNA) extracted from skin flap was analyzed to assess the messenger ribonucleic acid (mRNA) levels of different angiogenic growth factors. For skin flap viability experiment, fibrin film impregnated with vehicle, fibroblast growth factor (FGF) (5.0 microg) or vascular endothelial growth factor (VEGF) (2.0 microg) was applied to the wound. The skin flap was then returned to its native position and stapled in place. Total affected area (area of necrosis and blood flow stasis) of each rat on postoperative day 14 was analyzed with orthogonal polarization spectral imaging. Daily systemic treatment with sildenafil significantly (P < 0.05) increased the expression of FGF1 and FGF Receptor 3 on postoperative day 3 by 5.08- and 4.78 fold, respectively. In addition, sildenafil increased the expression of VEGF-A, VEGF-B, and VEGF-C by 2.66-, 2.02-, and 2.00-fold, respectively. Subcutaneous treatment with FGF but not VEGF-A tended to decrease total affected area in rats. These data demonstrate that sildenafil altered the expression of FGF and VEGF. Altered expression of growth factors may be, at least partly, responsible for the beneficial effects of sildenafil citrate on skin viability. PMID- 20583518 TI - Prior biliary tree instrumentation does not preclude hepatic arterial therapy for malignancy. AB - Hepatic arterial therapy (HAT) has become an accepted alternative for patients with unresectable hepatic malignancies. HAT has an acceptable toxicity profile, yet its safety for use in patients who have undergone significant biliary manipulation is undocumented. A retrospective review identified 18 consecutive patients with unresectable hepatic malignancies who had undergone significant prior biliary tree manipulation. All patients received peri-HAT antibiotics. Clinicopathologic, treatment-related, and outcomes data were collected and analyzed. Eighteen patients who had HAT were analyzed; 72 per cent were men, the median age was 61 years, and 61 per cent had greater than 25 per cent hepatic parenchymal replacement by tumor. Seventy-eight per cent of patients had an indwelling biliary stent and 22 per cent had undergone a hepaticojejunostomy. Twenty-two per cent of patients developed a complication, none of which were infectious, and there were no peri-HAT deaths. The majority of patients had evidence of either a partial response (55%) or stable disease (22%) upon follow up. One patient had a complete response to HAT. The median survival was 27 months. Hepatic arterial therapy seems to be safe for patients with unresectable hepatic malignancies and a history of significant biliary instrumentation. There is no increased risk of infectious complications in this population after HAT. PMID- 20583519 TI - Obstructed defecation after stapled hemorrhoidopexy: a report of four cases. AB - Stapled hemorrhoidopexy or Procedure for Prolapse and Hemorrhoids (PPH) has become an accepted alternative to excisional hemorrhoidectomy for treating prolapsing hemorrhoids. Although rare, severe complications have been reported after this procedure. We report a series of four male patients with the unusual but debilitating symptoms of obstructed defecation (OD) after PPH. Presenting symptoms included evacuation difficulty, rectal pain, and urgency. All had scarring and stenosis at their PPH anastomotic staple line with a resultant ball valve effect in three patients as the mobile, excessive, proximal rectal mucosa prolapsed past this relatively immobile area. The fourth patient had an anterior rectal mucosal pouch distal to the PPH staple line. In three of the four patients the anastomosis was below the dentate line or on an oblique angle. Corrective operative intervention largely relieved OD symptoms. One patient, more refractory to successful revision, was eventually diagnosed and treated successfully for pudendal neuropathy. Avoidance of the complication of OD is possible through careful patient selection, proper operative technique, and consideration of nonsurgical etiologies. These complications are complex in nature but most patients will respond to an individualized treatment plan that combines surgical and medical interventions. PMID- 20583520 TI - Laparoscopic common duct exploration in 90-bed rural hospital. AB - Laparoscopic common bile duct exploration (LCBDE) is an effective procedure when endoscopic retrograde cholangiopancreatography is not available. From January 2004 until December 2009, 1254 patients presented with biliary tract disease. Laparoscopic cholecystectomy was attempted in 1240 (98%) cases and completed in 1232 (98%) cases. Laparoscopic cholangiograms were performed in 627 (50%) cases. LCBDE was carried out in 33 (2.6%) cases. Of the 33 LCBDEs, 29 (2.3%) were via the cystic duct, four (0.32%) through a choledochotomy; eight (0.64%) of the total laparoscopic cholecystectomies were converted to open cholecystectomies. LCBDE can be done safely in small hospitals and is very useful when endoscopic retrograde cholangiopancreatography is not available. PMID- 20583521 TI - Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices? AB - Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer. PMID- 20583522 TI - Management of enteroatmospheric fistulae in the open abdomen. AB - There are few complications dreaded more by the general surgeon than the development of an enteroatmospheric fistula in the face of the open abdomen. The open abdomen has become a valuable tool in the treatment of trauma and complex surgical patients. The development of enteroatmospheric fistulae leads to increased cost, morbidity, and mortality. In our case series, we describe the use of Malecot catheters and early mobilization of skin and subcutaneous tissue flaps to manage enteroatmospheric fistulae. All of our patients were discharged from the hospital and did not develop any complications from the procedure. All of our patients' fistulae ultimately closed. This procedure could lead to decreased cost and morbidity. PMID- 20583523 TI - Analysis of demographic and tumor characteristics of an inner city breast cancer patient population compared with patients treated in National Surgical Adjuvant Breast and Bowel Project trials. AB - In June of 2008 we initiated a breast clinic designed to serve patients regardless of funding status. We analyzed age, race,tumor size, nodal status, estrogen, progesterone, and her-2-neu status. We compared our results to NSABP B 06 (nodal status), B-15 (estrogen, progesterone, and Her-2-neu receptor status), B-18, and B-27 (age, race, and tumor size) to determine whether our patient population was similar to patients included in these trials. Forty-nine patients with newly diagnosed breast cancer were treated during our first year (53 total cancers). Eight patients had noninvasive cancer; 45 had invasive disease. The mean age was 52.2 +/- 12.2 years compared to a mean age of 48.4 +/- 9.8 years in the B-06 trial (P = 0.005). Thirty six patients were African American (74%) compared to 10% and 12% in the NSABP B-18 and B-27 trials (P < 0.00001). A total of 23 of our patients with invasive cancer had involved axillary lymph nodes which was statistically more common than the 35.3% of node positive patients in the B-06 trial (P = 0.03). Tumor size (3.6 +/- 3.3 cm), estrogen (54.4%), and progesterone (52.8%) receptor status were similar to NSABP trials. Only 6 (13.3%) of our patients were considered Her-2-neu positive compared to 29.4% in the B-15 trial which was significantly less prevalent (P = 0.02). Significantly different demographic and tumor characteristics were identified in our inner city breast cancer patient population compared to NSABP patients. These results question the validity of using recommendations from large cooperative group trials in the development of treatment plans for our inner city patient population. PMID- 20583524 TI - Stapled intestinal anastomosis in neonates: validation of safety and efficacy. AB - The safety and effectiveness of a stapled intestinal anastomosis in adults and children is well documented. However, the role of this technique in neonates is not well validated. We report our experience with stapled intestinal anastomoses in the neonate at the University of Mississippi Medical Center. All patients from the neonatal intensive care unit who had a stapled intestinal anastomosis between February 2007 and May 2008 were identified. A stapled side-to-side functional end to-end intestinal anastomosis was performed in all patients using a gastrointestinal anastomosis stapler. Demographic, management, and outcome data were collected via chart review. Variables collected included: birth weight, estimated gestational age at birth and surgery, weight at surgery, the use of vasopressors, associated diagnoses, location of the anastomosis, and postoperative clinic visits. A total of 18 patients were identified during the study period. Nine had small bowel to small bowel, eight had ileum to colon, and one had a colon to colon anastomosis. The average weight at time of operation was 2.8 kilograms (Kg) and the average estimated gestational age at surgery was 38.7 weeks. The only complication reported was a partial small bowel obstruction on postoperative day 12, which was successfully treated nonoperatively. Two patients died from problems not associated with the anastomosis. There were no anastomotic leaks or strictures. The literature regarding the use of stapled bowel anastomoses in neonates is scant. Stapled intestinal anastomoses can be performed safely in neonates without a high rate of complication. The long-term effects of stapled intestinal anastomoses in the neonate are unknown. Future areas of interest would include effects on postoperative feeding and operative time. PMID- 20583525 TI - Ruptured colonic intramural hematoma with massive hemorrhage after aortic valve replacement. PMID- 20583526 TI - Hyperparathyroidism and pregnancy. PMID- 20583527 TI - Foreign body retention in the gut, an unusual pointer to annular pancreas. PMID- 20583528 TI - Fatal case of multi-drug resistant Acinetobacter baumannii necrotizing fasciitis. PMID- 20583529 TI - Amyloidosis of the colon: pitfalls in surgical management. PMID- 20583530 TI - Clinical presentation and management of liver adenoma hemorrhagic complications. PMID- 20583531 TI - Emergent pancreaticoduodenectomy for Dieulafoy lesion of the duodenum. PMID- 20583532 TI - Ruptured thoracoabdominal aneurysm with aortocaval fistula, aortic dissection type III, and bilateral femoral aneurysms in patient with Marfan syndrome. PMID- 20583533 TI - Combined open and endovascular repair of a DeBakey type IIIb dissection with complete distal true lumen occlusion. PMID- 20583534 TI - Sciatic hernia involving the ureter. PMID- 20583535 TI - Growth hormone testing nutrition and metabolic balance, do we have the full picture? PMID- 20583536 TI - Primary aldosteronism and its impact on the generation of arterial hypertension, endothelial injury and oxidative stress. AB - Aldosterone plays an important role in blood pressure homeostasis, the regulation of circulating volume, and the maintenance of the sodium-potassium balance by binding to the mineralocorticoid receptor (MR). Primary aldosteronism (PA) states are associated with an increased cardiovascular risk, mediated not only by hypertension but also by the action of aldosterone in the modulation of vasodilation/vasoconstriction and oxidative stress. In this review, we discuss some of the cardiovascular actions of aldosterone and the most frequent causes of PA. PMID- 20583537 TI - Metaphyseal condrodysplasia, Schmid-type, a differential diagnosis with rickets. PMID- 20583538 TI - Adiposity, physical activity and blood lipid profile in 13-year-old adolescents. AB - The main aim of this study was to determine the extent to which physical activity and adiposity are associated with blood cholesterol levels in male adolescents. Anthropometric and physical fitness values were measured in all children. Body mass index (BMI) and physical activity index (PAI) were used to split participants into active overweight (ACO) and non-active normal-weight (NAN) groups. The cutoffs for the ACO group were BMI > or = 22.6 kg/m2 and PAI > or = 3.5, respectively, whereas the corresponding cutoffs for the NAN groups were BMI < 20.0 kg/m2 and PAI < 2. A total of 65 children (29 in ACO group, 36 in NAN group) were selected according to the above criteria. ACO group showed significantly higher BMI and body fat as compared to their NAN counterparts (p < 0.05). Adolescents from ACO group attained superior scores for PAI and aerobic fitness (p < 0.05). Most blood lipid variables were significantly lower in ACO group as compared to NAN (p < 0.05) while HDL-cholesterol was higher in ACO group (p < 0.05). There was significant positive correlation between HDL-cholesterol and PAI in ACO group (r = 0.38; p < 0.05). The physical activity index explained the majority of variance in HDL-cholesterol for ACO group (beta = 0.513; p < 0.05). It seems that physical activity in adolescents is a more important factor in balancing blood lipid status than adiposity per se, particularly for HDL cholesterol. PMID- 20583539 TI - Relationship between metabolic parameters and thyroid hormones and the level of gastric peptides in children with autoimmune thyroid diseases. AB - Overweight and diseases connected with it are increasing problems in children and adults. We often observe change of weight in thyroid disease. It is emphasized that changes in hormones such as peptide levels are in close relationship with regulation of body mass: ghrelin increases appetite and in effect increases body mass, but obestatin decreases appetite and weight. The aim of the study was to analyze the relationship between lipid-carbohydrate metabolism parameters and thyroid hormones and the level of gastric peptides (ghrelin and obestatin) in young patients with Graves' disease, Hashimoto's thyroiditis and in children with simple goiter. The study group formed 78 patients suffering from Graves' disease (29 girls and 2 boys; aged from 6 to 21 - mean 15,2 yrs) and Hashimoto's thyroiditis (29 girls and 3 boys; aged from 9 to 18--mean 14.5 yrs). The control group consisted of children with simple goiter--13 girls and 2 boys; aged from 9 to 18 --mean 14.8 yrs. In all patients, ghrelin and obestatin levels were analyzed by the RIA method (Phoenix Pharmaceuticals, USA). In children and adolescents with untreated Graves' disease we found higher levels of insulin and HOMA-IR index compared to the group of children with simple goiter (34 +/- 8 microIU/mL vs 15 +/- 5; p < 0.03; 7.3 +/- 1.2 vs 3 +/- 0.3, p < 0.03). No significant correlations were observed of gastric hormones with antithyroid antibodies, lipids or h-CRP in patients with untreated hyperthyroidism and subclinical hypothyroidism. Positive correlation was noted of insulin and glucose levels and HOMA-IR index with ghrelin level in children with newly diagnosed Graves' disease (r = 0.109, p < 0.045; r = 0.176, p < 0.036; r = 0.174, p < 0.037). The correlation was also positive between obestatin level and HOMA-IR index in children with subclinical hypothyroidism in the course of Hashimoto's thyroiditis (r = 0.497, p < 0.011). We also examined the relationship between BMI, thyroid hormones and the level of gastric peptides. In untreated GD patients, ghrelin level exhibited a significant negative correlation with fT3 and fT4 (r = -0.38, p < 0.041; r = -0.459, p < 0.012) and positive with TSH (r = 0.38, p < 0.041) and BMI (r = 0.8, p < 0.01). In conclusion, we suggest that the disturbances in carbohydrate parameters in thyroid diseases have an essential effect on change of hormone-controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in Subclinical hypothyroidism). PMID- 20583540 TI - Stimulated growth hormone concentrations in obese pediatric patients with mild and severe insulin resistance: a pilot study. AB - BACKGROUND: GH excess predisposes to insulin resistance (IR). Obese patients have blunted responses to GH stimulation and decreased spontaneous secretion. GH secretion has not been studied in the context of IR.rr OBJECTIVE: To determine whether varying degrees of IR effects GH dynamics in obese children. PATIENTS/DESIGN: Patients (all > 10 y) were categorized according to gender and HOMA-IR to have either mild or severe IR. Twenty patients (10 female) with mild IR completed the study, as did 18 (9 female) in the severe group. Each patient underwent a GH stimulation test with GHRH. GH peak and area under the curve (AUC) were compared between the groups. RESULTS: Severe IR females had higher peak GH (mean +/- SD, 9.5 +/- 4.4 vs. 5.8 +/- 3.7 ng/dl, p = 0.04) and trended toward higher GH AUC (356 +/- 207 vs. 221 +/- 128, p = 0.06) than mild IR females. There were no differences in GH response in males, CONCLUSIONS: There may be a positive relationship between severity of IR and peak GH in obese girls. PMID- 20583541 TI - Amiodarone-induced thyrotoxicosis in children and adolescents is a possible outcome in patients with low iodine intake. AB - BACKGROUND/OBJECTIVE: The identification of the different subtypes of amiodarone induced thyrotoxicosis (AIT) may provide a rational basis for the choice of the appropriate medical treatment. The aim of this study was to evaluate differential diagnosis and treatment regimens of AIT in children and adolescent. PATIENTS: We reported 3 patients: A 6.7 years old boy with type I AIT; a 17.9 years old girl with type II AIT and a 14.6 years old girl with mixed type AIT. CONCLUSIONS: AIT is not an uncommon complication in countries with low iodine intake. AIT can be asymptomatic and can occur at any time in patients receiving amiodarone therapy. It is also very important to distinguish the type of AIT when planning therapy. Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued. PMID- 20583542 TI - Analysis of serum adiponectin, resistin and leptin levels in children and adolescents with autoimmune thyroid disorders. AB - Leptin, adiponectin and resistin, mainly produced by adipocytes, play a major role in body weight regulation. Disturbances in the maintenance of normal body weight are found to occur also in thyroid diseases. There is a close relationship of the changes in thyroid hormones with the contents of adipose tissue and adipocyte-secreted proteins regulating energetic metabolism in the body. The study objective was to analyze the levels of leptin, adiponectin and resistin in children with untreated Graves' disease, subclinical hypothyroidism in Hashimoto's thyroiditis and in children with simple goiter. The study involved 78 patients with Graves' disease (29 girls and 2 boys, aged 6-21 years, mean 15.2) and with Hashimoto's thyroiditis (30 girls and 2 boys, aged 9-18 years, mean 14.5). The control group consisted of adolescents with simple goiter (13 girls and 2 boys, aged 9-18 years, mean 14.8). The levels of leptin, adiponectin and resistin were determined using the ELISA method (R&D System, USA). Patients with untreated Graves' disease showed higher adiponectin level than the patients with hypothyroidism in Hashimoto's thyroiditis and in simple goiter (14.24 +/- 0.89 vs. 9.18 +/- 2.65, 10.15 +/- 2.5, p < 0.007, p < 0.01), but lower resistin level as compared to simple goiter and Hashimoto's thyroiditis (10.24 +/- 5.2 vs. 13.29 +/- 3.8, 12.2 +/- 2.8, p < 0.01, NS). The analysis of leptin levels revealed no significant differences between children with subclinical hypothyroidism and untreated Graves' disease (4.42 +/- 0.87 vs. 3.1 +/- 0.45 NS). In conclusion, we suggest that disturbances in thyroid hormones in thyroid diseases have an essential effect on the levels of adiponectin and resistin released by adipose tissue. PMID- 20583543 TI - Molecular diagnosis of 46,XY DSD and identification of a novel 8 nucleotide deletion in exon 1 of the SRD5A2 gene. AB - Phenotypic presentation of 46,XY DSD depends on the underlying defects. Defect in androgen action on the target tissues or production of active metabolite share common morphological features. Molecular study may help differentiating these abnormalities with precision. Mutational analysis of androgen receptor (AR) and SRD5A2 genes was performed in 29 patients with 46,XY DSD, by PCR-SSCP. The amplicons that showed an aberrant migration in SSCP were subjected to sequencing. Interestingly, six patients from 4 unrelated families (a pair of sibs, uncle/nephew and other two isolated) were identified with mutations in SRD5A2 gene. In five patients p.R246Q missense mutation was detected, of which four were homozygous and one was compound heterozygous: g.80_87delT CGCGAAG (p.A27fsX132) and p.R246Q. Another patient with isolated micropenis harbored a heterozygous p.G196S missense mutation. No AR gene mutation was detected. In conclusion, our study suggests that p.R246Q mutation is common amongst patients with SRD5A2 gene defect from the Northern states of India. Also, it records a novel deletion in exon 1 of SRD5A2 gene in a patient with severe hypospadias. PMID- 20583544 TI - Can auxology, IGF-I and IGFBP-3 measurements followed by MRI and genetic tests replace GH stimulation tests in the diagnosis of GH deficiency in children? AB - BACKGROUND/AIMS: GH levels < 10 ng/ml in response to two different GH stimulation tests (GHSTs) are traditionally used to identify children with GH deficiency (GHD). Since GHSTs are imprecise, other diagnostic tools have been proposed. We assessed whether auxology, IGF-I and IGFBP-3 measurements followed by brain MRI and genetic analysis can replace the current diagnostic approach. METHODS: Fifty three children diagnosed with GHD by two different GHSTs. GH-1 gene was sequenced. RESULTS: At presentation, 17% of patients were with height above -1.5 SD and 28% above -2.0 SD; 50% had IGF-1 concentration above -1.5 SD and 58% above -2.0 SD; 59% had pituitary anomalies demonstrated by MRI. Fourteen patients harbored the heterozygous R183H mutation, one patient had the N47D mutation and one had a novel F25Y mutation in GH-1. Using cut-off levels of -1.5 SD for height, IGF-I and IGFBP-3 excluded the diagnosis of GHD in 17, 68 and 79% of the children, respectively; a cut-off of -2 SD excluded 28, 88 and 96%, respectively. Further brain MRI and genetic tests excluded 81-96% and 96-100%, respectively, of children currently diagnosed with GH. CONCLUSION: Use of the tested approach, which avoids carrying out two GHSTs, would exclude most children currently diagnosed with GHD. Until better tools become available, we recommend identifying GHD in children by an integrated approach combining phenotype, auxological parameters, hormonal measurements and two separate GHSTs, with MRI and genetic tests to support the diagnosis. PMID- 20583545 TI - Body fat measurements in elite adolescent volleyball players: correlation between skinfold thickness, bioelectrical impedance analysis, air-displacement plethysmography, and body mass index percentiles. AB - BACKGROUND: Determination of body composition is an essential parameter in training athletes because low fat-muscle ratio might improve physical performance in many types of sports. Since training is often conducted in the field, it is important to determine whether simple field measurements of body composition assessment correlate with laboratory measurements. OBJECTIVE: Examine the correlation of body fat content as measured using skinfold thicknesses (SF), air displacement plethysmography (BOD POD), bioelectrical impedance analysis (BIA) and body mass index (BMI) age and gender adjusted percentiles. METHOD: Body mass as measured by SF, BOD POD, BIA, and BMI percentiles were examined in 29 elite, national team level, male and female volleyball players (age range 13 to 18) at the beginning of the training season. RESULTS: Body fat percent measured by SF, BIA and BOD POD were highly positively correlated (r > 0.83). Measurements of body fat by SF, BIA and BOD POD were weakly correlated with BMI percentiles (r < 0.45). CONCLUSIONS: Results suggest that BMI percentile is not a good measure for body fat in adolescent elite male and female volleyball players. SF and measurements of body composition by BIA and BOD POD are essentially interchangeable. PMID- 20583546 TI - Autonomic bladder dysfunction in an adolescent with type 1 diabetes. AB - Diabetic autonomic bladder dysfunction is rare in the pediatric age group. An adolescent girl aged 16 years and 7 months, with type 1 diabetes mellitus since the age of 6 years, was diagnosed as having diabetic cystopathy. Ultrasonography of the urinary tract showed a distended bladder with normal kidneys. Laboratory evaluation revealed: normal serum urea, creatinine and electrolytes and elevated microalbuminuria. Urodynamic study demonstrated an impaired bladder sensation, increased cystometric capacity and detrusor arreflexia. Although more prevalent in adults and the elderly, autonomic bladder dysfunction must be considered in adolescents with type 1 diabetes mellitus. PMID- 20583547 TI - Autoimmune thyroiditis and diabetes mellitus type 1 after long-term gonadotropin releasing hormone agonist treatment for central precocious puberty: evolution or coincidence? AB - Very few abnormalities in endocrine function have been reported during long term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. Most authors agree that this therapy is safe and effective. We present an unusual outcome of long term GnRHa therapy in two girls with central precocious puberty(CPP) of idiopathic or organic origin. They have received monthly depot injections of triptorelin acetate for a time period of 8 years. Thyroid function was examined by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies, and ultrasound of the thyroid gland. One of the girls was at the age of 8.5 years, having elevated thyroid antibodies, mild goitier and an abnormal ultrasound of the thyroid gland, suggesting autoimmune thyroiditis. Another girl with a hypothalamic hamartoma developed diabetes mellitus at the age of 9 years. Both of these girls were early diagnosed for CPP, at 6 months and 8 months respectively, and given GnRHa treatment. So far, it is not known whether these autoimmune diseases are related to the GnRHa treatment or are simply a coincidence. However, we suggest a closer monitoring of girls with CPP who have had a long period of treatment. PMID- 20583548 TI - Novel growth hormone receptor gene mutation in a patient with Laron syndrome. AB - Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation. PMID- 20583549 TI - A novel missense mutation in the AVPR2 gene of a Japanese infant with nephrogenic diabetes insipidus. AB - We describe an infant with nephrogenic diabetes insipidus (NDI) with a novel mutation in the arginine vasopressin receptor 2 (AVPR2) gene. A 1-month-old infant showed failure to thrive and hypernatremia. The water deprivation test revealed elevated serum osmolality and low urine osmolality. The patient showed a slight but not significant response to intramuscular injection of arginine vasopressin (AVP). DNA analysis revealed a novel missense mutation involving substitution of proline for leucine at position 173 (P173L), which was reported to be important for stabilizing the hydrogen bond between tyrosine at position 205 and leucine at position 169. This mutation was not detected in 116 ethnic matched controls. This case, with clinical data including the water deprivation test and P173L mutation, will facilitate understanding the structure and function of the A VPR2. PMID- 20583550 TI - Early presentation of familial paraganglioma with SDHB mutation in a 13 year old child and its mother. AB - Paragangliomas are extradadrenal neuroendocrine tumors, recently associated with gene mutations in the succinate dehydrogenase complex (SDH). These mutations are thought to be responsible for the familial paraganglioma syndrome. Average age of tumor diagnosis for SDH mutation carriers is about 30 years of age, but patients younger than 10 years have been reported. We present the case of a 13 year-old boy with abdominal paraganglioma, whose mother also had a history of thoracic paraganglioma diagnosed at 14 years of age. Both were found to carry a mutation in exon 4 of the SDHB gene, heterozygous for c.418G>T, p.Val140Phe sequence. Compared to the other SDH subtypes, SDHB associated tumors have been found to be much more aggressive. This has led to current recommendations that tumor screening of asymptomatic SDHB carriers should start as early as 10 years of age. An even earlier initiation seems warranted for the identified carriers in this family. PMID- 20583551 TI - [Hydrophilic regulator hexapeptides as inhibitors of tumor cell multiple drug resistance]. AB - Multiple drug resistance (MDR) of tumor cells to cytostatics is one of the most often and severe complications of chemotherapy in oncological patients. The phenomenon of MDR could be due to a sharp increase of the activity of the ATP dependent transport proteins of the ABC system, that provides pumping of the drug from the cells to the extracellular space. Up to now, all the attempts to design agents preventing MDR were of no success. One of the prospective trends is the use of hydrophilic regulator hexapeptides. Three regulator hydrophilic hexapeptides of the linear and cyclic structure were used as the MDR modulators. The sensitivity of the tumor cells to various cytostatics in the presence of the peptides was determined by the MTT-test and the direct counting of the survived cells. The effect of the hexapeptides on MCF7, KB8-5 and PC3 cells was investigated. It was concluded that the hydrophilic hexapeptides of the linear and cyclic structure increased the sensitivity to doxorubicin (a cytostatic). The tumor cell MDR inhibition was mediated by the ATP-dependent transport protein MRP. Such a characteristic of the hexapeptides is of interest for their use as agents preventing MDR. PMID- 20583552 TI - [Interferon inductor cupping of postvaccinal complications after variolation]. AB - Efficacy of arbidol and ridostin in cupping postvaccinal complications due to variolation was studied by the clinico-virological, hematological and biochemical indices and it was shown that arbidol was efficient in cupping development of dermal complications, lowered the severity of the postvaccinal reaction and stimulated the cellular and humoral immune response. Ridostin, a high molecular interferon inductor, was highly efficient in cupping all the forms of the postvaccinal complications, including the neurological and cutaneous ones. PMID- 20583553 TI - [Dynamics of beta-lactams resistance distribution in Streptococcus pneumoniae and its clinical significance]. PMID- 20583554 TI - [Dynamics of acquires resistance in the main gramnegative pathogens of surgical infections to beta-lactams in 2004-2008]. AB - Resistance of 2134 clinical isolates of etiologically significant species of gramnegative bacteria to 5 beta-lactam antibiotics, i. e. cefepime, piperacillin/tazobactam, cefoperazone/sulbactam, imipenem and ceftazidime (the 3rd generation cephalosporin) as the reference drug was investigated for the period of 5 years (2004-2008). In total, 554 strains of E. coli, 578 strains of P. aeruginosa, 255 strains of Acinetobacter spp., 161 strains of Proteus mirabilis, 359 strains of Klebsiella pneumoniae and 227 strains of Enterobacter cloacae were assayed in dynamics. The comparative analysis of the frequency of the antibiotic resistant isolates from the patients treated within 2004-2008 with often and long-term use of cefoperazom-sulbactam, meropenem and imipenem revealed an increase in development of resistance to all beta-lactams, including the inhibitor-protected ones. It least of all concerned imipenem, still isolation of 39.5% of the imipenem resistant strains of P. aeruginosa was in favour of the tendency. A dramatic 3-5-fold rise of resistance in 2007 and 2008 in the isolates of K. pneumoniae, E. cloacae and Acinetobacter spp. to both the inhibitor protected beta-lactams, that averaged 56 and 45%, 45 and 35% and 26 and 30% respectively, deserved attention. It was assumed that the main mechanism of resistance in the isolates to the inhibitor-protected beta-lactams was hyperproduction of beta-lactamase of type CTX-M. The large part of the cefepime resistant isolates of K. pneumoniae and Acinetobacter spp. (76.8 and 62.2% respectively) was in favour of the assumption. It was concluded that periodical reversion of the policy of preventive antibiotic prophylaxis was necessary, since such a prophylaxis is a reliable barrier to development of postoperative complications and at the same time it promotes selection of nosocomial strains with some other mechanisms of antibiotic resistance under hospital conditions. PMID- 20583555 TI - [Cycloferon efficacy in the treatment of acute respiratory tract viral infection and influenza during the morbidity outbreak in 2009-2010]. AB - Clinical signs of acute respiratory tract viral infection and influenza in 150 patients under the standard symptomatic therapy with cycloferon, an early interferon 1 and 2 inductor are described. The patients were randomized by the body temperature on the day of the medical advise seeking. The clinical process of the respiratory tract infection was characterized by the second increase of the body temperature stated in 31.8% of the patients. By the clinical signs the infection was mixed (virus-virus) that explained the second increase of the body temperature. Normalization of the temperature was stated on the 4th or 5th day of the observation. The catarrhal and intoxication syndromes were observed for no more than 5 days. When the treatment was started in time (on the day of the medical advise seeking), cycloferon provided minimization of the intoxication and catarrhal syndromes and normalization of the body temperature on the 4th day of the therapy without the use of antibacterial agents. PMID- 20583556 TI - [Efficacy of cytoflavin in therapy of encephalophathy in patients with neuroinfection]. AB - The use of cytoflavin solution in complex therapy of patients with neuroinfection was studied. It showed a favourable effect on the disease clinical process, evident from less pronounced intoxication and meningeal signs by the 11th day of the treatment and improvement of the liquorological picture. The cytoflavin efficacy was also confirmed by normalization of the brain bioelectric activity evident from the electroencephalograms and by reduction of the level of antioxidants, such as metalloproteids and superoxidodismutase, that was in favour of the drug antiinflammatory and antioxidant effects. The use of cytoflavin tablets during in early convalescence period promoted earlier recovery of the intellectual and mnestic reactions. On the whole, the use of cytoflavin promoted favourable process and outcomes of neuroinfections and could be recommended for the use during the acute state and re habilitation of the patients. PMID- 20583557 TI - [Resistance of antibiotic-producing actinomycetes to their own antibiotics]. PMID- 20583558 TI - [Antibiotic resistance in hospital: do we control the situation?]. PMID- 20583559 TI - [Kinetic and equilibrium parameters of erythromycin sorption on various sorbents]. AB - Optimal conditions for erythromycin sorption on supercoupled isoporous Purolight sorbents (styrosorbs) S-106, S-150 and S-160 and on macroporous sulfocation exchanger KU-23 were determined. High selectivity of erythromycin sorption on the supercoupled isoporous cation exchanger S-106 was shown, that was evident from the high distribution coefficient. The effective diffusion coefficient on the cation exchanger S-106 was higher by a factor of 10(2) (1.1 x 10(-11) m2/s) that was in favour of a comparatively high diffusion rate. PMID- 20583560 TI - [Fermentative production of 1,3;1,6-beta-D-glucan (translam), a labeled immunostimulant and investigation of its pharmacokinetics and pharmacodynamics]. AB - Production of labeled translam from a marine mollusk was provided by the use 1,3 beta-D-glucanase. The pharmacokinetics of the 14C-translam metabolism in the experimental rats by the accumulation level and the retention time in the organs and tissue and the excretion rate with the feces and urine was of the same character as that of carbohydrates and in particular that of glucose, whereas the excretion of translam mainly with the urine was likely evident of its incomplete hydrolysis after the intramuscular administration. PMID- 20583561 TI - [Antibiotics produced by Photorhabdus luminescens ZMI, a symbiont of entomopathogenic nematodes]. AB - A novel strain of Photorhabdus luminescens ZMI isolated from nematode larvae Heterorhabditis sp. was shown to produce antibiotic complexes with antibacterial and antifungal activities. The antibiotic complexes secreted extracellularly and intracellularly were separated into individual components. Comparison of their properties with the databases for biologically active compounds suggested that component A was identical to 3,5-dihydroxy-4-isopropylstilbene, components B and H belonged to anthraquinone derivatives, component C secreted only extracellularly was likely a novel antibiotic. PMID- 20583562 TI - [Ribavirin prophylaxis and therapy of experimental West Nile fever]. AB - Investigation of the efficacy of ribavirin against the West Nile virus in standard cell cultures showed that in high concentrations it inhibited the virus reproduction (the inhibition coefficient of 100%). In the experiments on albino mice infected with the West Nile virus in a dose of 10 LD50 ribavirin was used in the form of injections in a dose of 20 mg/kg for 7 days in the scheme of urgent prophylaxis and proved to be highly efficient in protection of the animals from death (85-percent survival). PMID- 20583563 TI - [Hepatoprotective effect of hepatophyt in experimental drug hepatitis]. AB - The hepatoprotective action of Hepatophyt was studied on Wistar rats with experimental hepatitis caused by exposure of the animals to tetracycline. Hepatophyt was administered per os in a dose of 0.1 g/kg. Its significant pharmacotherapeutic action was due to the content of biologically active substances, mainly of polyphenol nature. As natural antioxidants, they provided stabilization of the biomembranes and increased the energetic potential of the hepatic cells and the contractile capacity of the pericanal microfilaments, thus stimulating the synthesis and transport of the cholates and excretion of bilirubin and cholesterol with bile. PMID- 20583564 TI - [Antibiotic resistance of gramnegative nosocomial pathogens in Minsk ICUs]. AB - The species pattern and antibiotic resistance of gramnegative isolates from patients with nosocomial infections in Minsk ICUs were studied. Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli were the main pathogens, highly resistant to the antibiotics used. Imipenem, meropenem, polymyxin B, ampicillin/sulbactam, amikacin and cefoperazone/sulbactam were the most active antimicrobials against the isolates. The choice of antimicrobials for empirical therapy of hospital infections in ICUs should be based on the local situation regarding the antibiotic resistance, that makes it obligatory to use regular microbiological monitoring in all hospitals thus providing the policy of the use of antimicrobials in ICUs. PMID- 20583565 TI - [Optimization of the treatment of patients with chronic cardiac insufficiency and cardiopulmonary pathology]. PMID- 20583566 TI - [Safety of floracid (levofloxacin), a Russian antimicrobial, in the treatment of outpatients]. PMID- 20583567 TI - [Mechanism of action of macrolide antibiotic filipin on cell and lipid membranes]. AB - The review deals with investigation of the mechanism of action of macrolide pentaene antibiotic filipin on cell and bilayer lipid membranes (BLM). The sterol hypothesis of the filipin mechanism of action is confirmed experimentally. The hemolytic and geneticocytological action of filipin, its action on virus infection and prion protein-associated diseases are discussed. The data on the mechanism of filipin action on BLM are presented. Filipin single ionic channels with conductance of 15-20 pS that is 3-4 times higher than that of the amphotericin channels were detected on cholesterol-containing membranes in filipin low concentration (1 x 10(-8) M) aqueous salt solution. Combined ionic channels of filipin and amphotericin B with conductance of 25-30 pS, that is 1.5 2 time lower than that of the clean filipin channels and 5 times higher that of the clean amphotericin B channels were also detected. The selectivity of filipin channels is mainly cationic. The potential of the penetrating ion on 10-fold gradient is +18 mV. The practical aspects of filipin application in biology, medicine and pharmacology are indicated. PMID- 20583568 TI - [Fatty acid of human plasma under the influence of acute strong normobaric hypoxia]. AB - The influence of acute normobaric hypoxia on total pool of human plasma fatty acids was studied in experiment (respiration of hypoxic gas mixture containing 8% of O2, during 25 min). Health status of participants-volunteers and the hypoxia intensity were monitored with a complex of electrophysiological methods: EEC, ECG, measurement of blood pressure, SpO2, evaluation of cardiac output, gas analysis of exhaled air. Using gas chromatography we studied plasma fatty acids total profile (esterificated and non-esterificated) before hypoxia exposure, on 2nd, 5th, 10th, 20th minutes of acute hypoxia and on 5th and 15th minutes of recovery. It was shown that blood saturation value dropped to 52.1 +/- 7.1 % on 25th minute of hypoxia exposure. There were no statistically significant changes in concentrations of total fatty acids, saturated fatty acids, monounsaturated palmitoleic acid, polyunsaturated linoleic and linolenic acids. Significant (p < 0.05) decrease of concentration of oleic and arachidonic acids was displayed that persisted after 15 minutes of recovery period. It is possible to assume that these changes in unsaturated fatty acid concentration were caused by activation of free radical oxidation processes and production of oleic acid derivatives. The performed hypoxic test seemed to be sufficient in order to reveal hypoxia effects on metabolism of individual unsaturated fatty acids. PMID- 20583569 TI - [Disruption of latent inhibition in adult rats after prepubertal dopamine terminals lesions in the ventral hippocampus]. AB - Wistar rats were submitted to bilateral ventral hippocampal injection of 6 hydroxydopamine on 32nd day after birth. Latent inhibition was measured in passive or active avoidance tasks when the rats received 20 and 100 pre-exposures of conditioned stimulus. Prepubertal and adult lesioned rats showed a deficit in the latent inhibition but not in the capacity to avoidance learning in presence of the conditioned stimulus novelty. Possible mechanism of the involvement of hippocampal dopaminergic terminals in attention inhibition to irrelevant information is considered. PMID- 20583570 TI - [Study of the association between catalepsy, anxiety, aggression and depressive like behavior in congenic mice]. AB - Catalepsy is a natural passive defense strategy in animals and a syndrome of some mental di sorders. The main gene encoding catalepsy was located in mice on the distal fragment 55-75 cM of chromosome 13. Two congenic lines AKR.CBA-D13Mit76 and AKR.CBA-D 13Mit78 carrying the 55- to 71-, and 71- to 75-cM fragments of chromosome 13 transferred from the cataleptic strain CBA to the non-cataleptic strain AKR genome were created. It was shown that half of mice of congenic AKR.CBA-D 13 Mit76 line containing fragment 55-71 cM displayed pronounced catalepsy similar to the donor CBA strain. Also we demonstrated decreased of exploratory behavior in the open field test and an increased of intermale aggression of AKR.CBA-D 13Mit76 mice compared with the parent strain AKR. No differences were found in the forced swim test between AKR.CBA-D 13Mit76 and AKR mice. Behavior of congenic mice AKR.CBA-D 13Mit78 did not differ from the parent strain AKR in all used tests. PMID- 20583571 TI - [Role of heat shock proteins, aldose reductase, Bcl-2 protein and microRNA in the mechanism of delayed preconditioning of heart]. AB - Analysis of published data allows affirming that heat shock proteins (HSP) play an important role in the mechanism of cardioprotective effect of delayed preconditioning. However, HSP in all probability are non-end effectors but mediators of preconditioning because a peak of their levels in myocardium does not concur with maximal elevation of cardiac tolerance to impact of ischemia and reperfusion. There are bases to think that aldose reductase and Bcl-2 protein are claimants to the role of end-effectors of delayed preconditioning but microRNAs serve as mediators of forming increased cardiac tolerance to ischemia reperfusion. PMID- 20583572 TI - [NO-dependent. Modulation of contractile function in capsule of lymph nodes]. AB - Phase and tonic contractions of capsular smooth muscles of bovine mesenteric lymph nodes were studied in vitro. Smooth muscle cells of the node capsule demonstrated spontaneous contractile activity; frequency of spontaneous phase contractions was averaged 1.1 +/- 0.14 min(-1), amplitude 1.7 +/- 0.21 mH. Sodium nitroprusside (0.1-1 microM) and acethylcholine (1 microM) reduced frequency and amplitude of phase contractions of smooth muscles of the lymph node, sodium nitroprusside (1 microM) arrested spontaneous contractile activity completely and decreased tone of the smooth muscle cells. Preliminary incubation of tissues with L-NAME, methylene blue or glibenclamide reduced the relaxation effect of acethylcholine considerably. We suggest that endothelial cells of subcapsular sinus of the lymph node produce NO which results in opening of ATP-sensitive K(+) channels of smooth muscle cell membrane by means of cascade reaction and the relaxation of smooth muscle. PMID- 20583573 TI - [Neuronal mechanisms of voluntary and involuntary movements in parafascicular (CM PF) thalamic complex in spasmodic torticollis patients]. AB - Activity of 144 parafascicular CM-Pf thalamic neurons was studied and recorded by means of microelectrodes during 18 stereotactical neurosurgical operations in spasmodic torticollis patients. High reactivity of two previously classified neurons with single sporadic activity (A-type) and bursts of Ca2(+)-dependent activity (B-type) were found during verbally ordered voluntary movements. There are coordinated reciprocal activation-inhibition A-type and B-type neuronal responses at the stage of verbal command presentation and synergic activation responses on the high of movement and in the aftereffect. Voluntary movement realization was accompanied by short-term local synchronization and stabilization of oscillatory (3-5 Hz) neuronal activity. The neuronal response differences between voluntary movements with and without neck muscle exertion and involuntary pathological movements prove the CM-Pf involvement in the pathology of spasmodic torticollis desease. PMID- 20583574 TI - [Experimental approaches to research role of genotype in locus TAG 1A of gene receptor dopamine second type in narcotic dependence]. AB - The aim of this study was investigation into influence of genotype in locus TAG 1A of gene receptor dopamine second type on mechanisms forming narcotic dependence. Study of water schedule and behavior in "open field" test before and after compulsory alcoholization was performed on two groups of adult rats with genotypes A1/A1 and A2/A2 in locus TAG 1A. The results obtained suggest the effect that allele A1 (or genotype A1/A1) in locus TAG 1A of gene receptor dopamine second type exerts upon accelerated development of alcohol tolerance and forming of narcotic dependence. These results also confirm previously obtained data on association of allele A1 in locus TAG 1A of gene receptor dopamine second type with hard clinical course of alcoholism and narcotic dependence. PMID- 20583575 TI - [Interrelation of hemodynamic changes in systemic and pulmonary circulation under experimental myocardial ischemia in cats]. AB - Myocardial ischemia caused inhibition of myocardial contractility, increased pressure in the left atrium, reduced cardiac output and reduced systemic blood pressure. The decrease in cardiac output is due to a combination of the myocardial contractility reduction and that of the outflow of blood from the pulmonary vascular bed. Hemodynamic changes in the arterial part of the systemic circulation are accompanied by shifts in its venous part: reduced blood flow in the anterior and posterior caval veins and a decrease in venous return. The determining factor for reducing the flow of venous blood to the heart during myocardial ischemia is a decrease in cardiac output. Myocardial ischemia of the left ventricle is accompanied by a decrease in pressure and blood flow in the pulmonary artery. The data obtained suggest that the degree of reduction of these indicators of pulmonary hemodynamics depends on the elevated pressure in the left atrium resulting from reduction of the left ventricle contractility. The degree of hemodynamic disorders in systemic and pulmonary circulation in myocardial ischemia depends not only on the size of the zone of myocardial ischemia of the left ventricle, but also on the duration of cessation of its blood supply. We suggest that the time factor is a decisive one with respect to severity of hemodynamic disorders occurring only at a certain, critical, size of the zone of myocardial ischemia. PMID- 20583576 TI - [The regulatory role of the oxide nitrogen and monoxide carbon under oxidative stress in experimental dyslipidemia]. AB - The condition of the system "prooxidants-antioxidants" in dynamic model alimentary dyslipidemia in Vistar rats of the lines were studied. General antioxidant activities, activities of antioxidant enzymes (katalase, glutathione reductase, glutathione peroxidase), levels of glutathione, products of lipoperoxides in blood and liver, intensive forming of the oxide nitrogen and monoxide carbon were investigated. The role of the signal molecules (oxide nitrogen and monoxide carbon) in regulation oxidative stress was discussed. It is shown that breach of the dynamic balance between synthesis of oxide nitrogen and monoxide carbon displaces the compensation response in the "prooxidants antioxidants" system. The reinforcement formation of monoxide carbon decreases synthesis of oxide nitrogen by cells, activation of the lipoperoxidation processes, progressive oxidative stress, apoptosis induction signal. PMID- 20583577 TI - [The blood acid-base values of various qualifying groups of sportsmen in physiological condition and in exercise]. AB - The acid-base parameters and buffer systems of blood of different qualifying groups of sportsmen in physiological condition and at physical work were studied. It is shown that initial differences of the acid-basic condition and buffer capacity of integral blood of sportsmen of high qualifying group lead to changes of the pH dynamics at raising concentration of lactate. Dynamics of the blood lactate concentration is analyzed at stepped-raising exercise in sportsmen of different qualification, the possible molecular mechanism of sharp increase in concentration of lactate in the blood is discussed. It is shown that the point of a break on a curve of change of the pH precedes a point of break on a curve of increase in concentration of lactate at physical work. The received results can be used for definition of the moment of approach of an anaerobic threshold with pH-measurement of the blood. PMID- 20583578 TI - [Comparative study of substrate and inhibitory specificity of monoamine oxidase in the optic ganglia of squids]. AB - Comparative study of substrate specificity of monoamine oxidase (MAO) of optic ganglia of the Pacific squid Todarodes pacificus and the Commander squid Berryteuthis magister has been carried out. The enzyme of the Pacific squid, unlike that of the Commander squid, has been established to be able to deaminate not only tyramine, tryptamine, serotonin, benzylamine, and beta-phenylethylamine, but also histamine--substrate of diamine oxidase (DAO). In relation to all studied substrates, the MAO activity of optic ganglia of T. pacificus is several times higher as compared with B. magister. In the case of deamination of serotonin this difference was the greatest and amounted to 5 times. Semicarbazide, the classic DAO inhibitor, at a concentration of 10 mM did not inhibit catalytic activity of both studied enzymes. The substrate-inhibitory analysis with use of deprenyl and chlorogiline, specific inhibitors of different MAO forms, indicates homogeneity of the enzyme of the Pacific squid and heterogeneity of the Commander squid enzyme whose composition seems probably to contain at least two MAO forms. There are obtained quantitative differences in substrate specificity and reaction capability with respect to the inhibitors chlorgiline and deprenyl for MAO of optic ganglia of the studied squid species. These differences probably can be explained by significant differences in the evolutionary level of these biological species. PMID- 20583580 TI - [Evaluation of functional state of crayfish Pontastacus leptodactylus in normal and toxic environment by characteristics of their cardiac activity and hemolymph biochemical parameters]. AB - The work deals with study of basic characteristics of cardiac activity (HR and stress-index) and hemolymph protein parameters in the crayfish Pontastacus leptodactylus. The main criteria of the crayfish selection are developed for formation of the animal reference groups available for subsequent toxicologic experiments. The action of a model toxicant, hydroquinone (often present in waste water), at a concentration of 1 g/l on parameters of the crayfish cardiac activity at various exposition time, its effect on circadian cardiac activity and on the hemolymph total protein were studied. At its short-term exposure, hydroquinone produced a temporary increase of HR and stress-index, but had no marked effect on the total protein parameters in hemolymph. At long action (for one day), hydroquinone led to a considerable tachycardia, disturbance of the circadian cardioactivity and to a decrease by 40% of the hemolymph total protein. In 50% of cases the toxicant caused death of the animals either in the course of its action or at period of washout from the toxicant. Mechanisms of the toxic action of hydroquinone at various levels of organization are discussed. PMID- 20583579 TI - [Transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis]. AB - Mechanisms of transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis were studied by using 204Tl. Transport of Tl+ in lamprey oocytes has been shown to be realized by at least two pathways: through Na/K-pump and by the mechanism of Na,K,Cl-cotransport. In the standard Ringer solution (mM): 4 KCl, 140 NaCl, 0.5 CaCl2, 5 glucose, 10 Tris-HCl--in the presence of oubain, the coefficient of the 204Tl stationary distribution (cell/medium) was within the range of 2.3-2.5, while the time necessary to reach its 50 % value amounted to 40-5 min at 20 degrees C. In potassium-free media, transport of 204Tl via Na/K-pump was described by simple kinetis with saturation and was characterized by the value V(max) = 520 pmol/(cell x h) and K(M) = 0.3 mM. In the presence of 4 mM K+ and 0.1 mM/l Tl+, the oubain-sensitive Tl+ flow decreased to 75 pmol/(cell x h). At activation of the mechanism of Na,K,Cl cotransport by the outer Na+ (in Na-NMDG media of different composition) the total inflow of Tl+ reached 193 +/- 20 pmol/(cell x h), while the butamenide sensitive component--119 +/- 12 pmol/(cell x h) with K(M) for Na+ about 20 mM. In the incubation media with variable concentration of chloride ions (replacement of Cl- by NO3(-)) the total Tl+ flow reached 220 +/- 21, while via the mechanisms of Na,K,Cl-cotransport--87 +/- 8 pmol/(cell x h). Under our experimental conditions, mechanisms of active transport and Na,K,Cl-cotransport accounted for 94% of the Tl+ inflow. The potassium channels that usually are also permeable to monovalent thallium ions were not revealed. PMID- 20583581 TI - [Metabotropic glutamate receptors in the mechanisms of plasticity of central nervous system of the honeybee Apis mellifera]. AB - Localization of metabotropic glutamate receptors (MGR) in head ganglion of honeybee Apis mellifera, and mechanisms of participation of activated MGR in CNS plasticity are investigated by means of complex approach using immunochemical, electrophysiological and behavioral methods. Influense of MGR activation on GABAergic system and ionotropic glutamate receptors (IGR) of AMPA- and NMDA subtypes in studied. MGRa are revealed in lateral and medial calices of mushroom bodies. The inhibiting influence of MGR on AMPA- and NMDA receptors is shown using method of conditioned reflex. Previous activation of MGR neutralizes the inhibiting effect of GABA. Modulating role of heterogeneous MGR population in mechanisms of CNS plasticity on the level of glutamate-ergic synapse, and at interaction with GABAergic system is discussed. PMID- 20583582 TI - [Effect of harmaline of the complex spike waveform and depression time in cerebellar Purkinje cell discharge in rat postnatal ontogenesis]. AB - Functional relationship between waveform of complex spike (CS) and depression time of simple spike (SS) in discharge of cerebellar Purkinje cells was studied after their activation with afferent climbing fiber at different terms of postnatal ontogenesis in norm and after treatment with harmaline. The experiments were carried out on three age groups of Wistar rats: rat pups (2 weeks), the adult (4-6 months), and the old animals (22-26 months). It was established that the CS duration in norm was approximately equal in rat pups, adult, and old animals, whereas it markedly decreased from the young to the old animals during the SS depression in the Purkinje cell discharge. Frequency of small action potential (sAP) and their number in the Purkinje cell discharge were approximately equal in young rat pups and adult animals, while in old animals these parameters were higher, on average, by 30%. After administration of harmaline, all CS parameters in rat pups and old animals increased in parallel with the depression time elongation. In adult rats, harmaline did not produce statistically significant changes of the mean values of CS parameters, but an increase of the simple spike depression time was observed. The obtained results allow concluding that the CS waveform and the simple spike depression time in norm are functionally coupled and change with age. The effect of harmaline on the CS waveforms as well as on interrelation of the CS duration and the SS depression time in the Purkinje cell discharge was more pronounced at the early and the late stages of Wistar rat postnatal ontogenesis. PMID- 20583583 TI - [Effect of copper ions on spatial density of NO-synthase-positive cells in the intestine of the mussel Crenomytilus grayanus (Mollusca: Bivalvia: Mytilidae) a histochemical study]. AB - By the histochemical method of detection of NADPH-diaphorase (NADPH-d) (EC 1.6.99.1) the state of nitroxidergic enteric nervous system of the mussel Crenomytilus grayanus was studied under conditions of an increased copper concentration in water. Under the action of copper ions the density of distribution of NADPH-d-positive cells has been established to be changed as compared with control throughout 28 days. A sharp rise of proportion of the labeled cells and their enzyme activity was noted after one day of the experiment. The labeled bipolar cells were of dark blue color and were located within the epithelium. There were revealed numerous nerve fibers penetrating the intestinal epithelium throughout its entire length as well as bipolar nerve cells in epithelium of the minor typhlosole and of crystalline style sac; in control molluscs the NADPH-d-positive cells in these parts were absent. After 7 days the difference between control and experimental decreased and remained at this level after 14 days, while after 21 days of exposition the proportion of labeled cells in the experimental mussels was lower than in control, but increased again after 28 days. It is suggested that nitric oxide is an important protective factor of the intestinal epithelium of the mussel C. grayanus and participates in adaptation of this mollusc to action of the elevated concentration of copper ions in water. PMID- 20583584 TI - [Expression of contractile proteins alpha-actin and myosin of smooth muscle cells and collagen of IV type in human placenta at placental insufficiency in III trimester of pregnancy]. AB - Changes of expression of contractile proteins (alpha-actin and myosin of smooth muscle cell) and of collagen of IV type in stroma of human placental villi were studied at the diagnosed placental insufficiency (PI) in III trimester of pregnancy. The study revealed pronounced disturbances of expression of contractile proteins and collagen of IV type at PI. It is shown that in perivascular envelopes of vessels of stem and intermediate villi there is present a much greater amount of cells expressing smooth muscle actin and myosin. These cells are arranged by the denser concentric layers and more compactly than in norm and fill the intervascular space inside the villi. The width of perivascular envelopes of vessels is higher, while vascular lumens are lower than in norm. In terminal villi the capillary walls are thickened and the number of pericytes immunopositive against the smooth muscle cell alpha-actin and myosin as well as collagen of IV type is increased. The change of synthesis of the cytoskeletal contractile proteins and collagen of IV type is shown to lead to structural disturbances of villi of different types and of perivascular areas and vessels, which doubtlessly indicates their participation in pathogenesis of placental dysfunction and of disturbance of placental hemodynamics. PMID- 20583585 TI - [Functional approach to the problem of treatment of diseases caused by highly mobile protists]. PMID- 20583586 TI - [Effect of insulin on some characteristics of the food-procuring activity of the crucian carp Carassius carassius]. PMID- 20583587 TI - [Buffer, respiratory properties, and ion surrounding of hemoglobin in the sterlet Acipenser ruthenus]. PMID- 20583588 TI - [Lateral peculiarities of the process of mental spinning of the scheme of human body]. PMID- 20583589 TI - [Effect of processes in the earth's crust on evolution of photosynthesis (as indicated by data on carbon isotopic composition)]. AB - A probable mechanism of effect of processes occurring in the Earth's crust on evolution of photosynthesis is considered. According to the hypothesis, this effect is realized through entrance to the Earth's atmosphere of carbon dioxide that stimulates photosynthesis. Supply of CO2 is irregular and is due to irregular movements of the Earth's crust plates. This is accompanied by destruction of carbonates and conversion of carbon of the organic matter to CO2 due to processes of reduction of sulfates. The CO2 content in atmosphere rises for relatively short orogenic periods, due to intensive crust plate movement, while for the subsequent long periods, called the geosynclinal ones, of the relatively slow plate movement, the CO2 content falls due to the higher rate of its consumption for photosynthesis. Owing to the carbon isotopic fractionation accompanying photosynthesis, regular isotopic differences appear between the atmospheric CO2 and the "living" matter (Relay's effect); these differences are then transformed to isotope differences of the carbonate and organic carbon. At the appearance in atmosphere of free oxygen--product of photosynthesis--in organisms there appears photorespiration that also is accompanied by fractionation of carbon isotopes, but with effect of opposite sign. This leads to enrichment of the photosynthesizing biomass with 13C isotope at the orogenic periods. As a result, the initially pronounced isotope differences of the carbonate and organic carbon decrease by the end of the geosyclinal periods. According to the proposed model, concentrations of CO2 and O2 are exchanged in the antiphase. They lead to alternation of periods of warning up and cooling off on the Earth. The former coincide with the orogenic periods, the latter appear at the end of geosyclinal periods when oxygen is accumulated in atmosphere, while organic substance in sediments. Accumulation of organic substance leads to formation of petroleum-maternal masses. To substantiate the model, data on isotope composition of carbon of carbonate and organic substance in rocks are used and its ability to explain several known natural regularities and empirical correlations. The model is used for analysis of some key stages of evolution of photosynthesis. PMID- 20583590 TI - [Hypothesis of evolutionary origin of several human and animal diseases]. AB - Studies of our Laboratory in the field of molecular and evolutionary endocrinology have allowed us to put forward a hypothesis about evolutionary origin of endocrine and other diseases of human and animals. This hypothesis is considered using a model of hormonal signal systems. It is based on the concept formulated by the authors about molecular defects in hormonal signal systems as the key causes of endocrine diseases; on evolutionary conservatism of hormonal signal systems, which stems logically from the authors' concept of the prokaryotic origin and endosymbiotic appearance in the course of evolution of chemosignal systems in the higher eukaryotes; from the fact that the process of formation of hormonal signal systems with participation of endosymbiosis including the horizontal transfer of genes is accompanied by transfer not only of normal, but also of the defected genetic material. There are considered examples of the principal possibility of transfer of defected genes between bacteria and eukaryotic organisms. Analysis of the current literature allows suggesting inheritance of pathogenic factors from evolutionary ancestors in the lineage prokaryotes--lower eukaryotes--higher eukaryotes. PMID- 20583591 TI - [Multiform wave organization of neurophysiological processes--universal "language" of human brain in realization of informational-controlling functions]. AB - There are summarized literature data and results of many-year Laboratory studies disclosing principles of multiform spatial-temporal organization of different by rates neurophysiologic brain processes as the universal "language" of its informational-controlling functions. Current concepts of electrogenesis and physiological significance of ratios of gradual changes of biopotentials and impulse activity of neurons are considered in studies of cerebral mechanisms of regulation of normal and pathological states, organization of human psychic activity. Proposed and argumented is the concept of probability principle of hierarchical organization of different by rates neurophysiologic processes of the brain zones, structures, and areas in formation of the brain systems participating in provision of the higher psychic functions and states. It is proposed to discuss the concept of the brain as the "swimming", many-contour, neurodynamic informational-controlling suprasystem with universal, hierarchically organized neurodynamic structures--"functional organs" after A. A. Ukhtomskii (1978), of which formation provides an extensive informational brain capacity and a large specter of adaptive possibilities of the human organism. PMID- 20583592 TI - [Transcriptional gene silencing in plants]. AB - The review presents current data on molecular genetic mechanisms of suppression of the gene (transgene) expression in plants at the transcriptional level. The stages of RNA-directed DNA methylation are discussed in detail. Mutations affecting transcriptional gene inactivation without altering nucleotide sequence methylation are described. PMID- 20583593 TI - [Functional interaction between an insulator and a Pc-dependent silencer with the example of the Mcp boundary of the Drosophila melanogaster Abd-B gene]. AB - Insulators are cis-regulatory elements that prevent improper gene activation and heterochromatin spreading. An insulator is contained in the Mcp boundary from the regulatory region of the Drosophila melanogaster Abd-B gene. The barrier function of the Mcp insulator was studied and proved to be due to two modules. One is responsible for long-distance interactions and the capability of blocking enhancers. The other is essential for blocking Pc-dependent repression. It was observed for the first time that an insulator increased the repressor activity of a neighbor silencer. PMID- 20583594 TI - Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136. AB - LanK is TetR-like regulatory protein recently shown to regulate the export and glycosylation of landomycins in Streptomyces cyanogenus S136. Here, several properties of the lanK-mediated regulation were deciphered. LanK seems to function as oligomer as evident from experiments in vitro. In vivo, it is able to recognize various landomycins with altered aglycon structure and the minimal concentration of landomycin A sensed by LanK lies in low nanomolar range. Coexpression studies showed that the positive regulatory gene lanI upregulates lanK-dependent lan genes once the negative LanK-regulation is cancelled. Gene lanK can be useful for the construction of biosensor strains for sensitive and specific identification of producers of landomycin-like molecules with long glycosidic chains. PMID- 20583595 TI - [Phenotypic switching of Escherichia coli cells containing cyclic digenic systems with negative feedback upon changes in cultivation conditions]. AB - One of the mechanisms for the epigenetic control of cell phenotypes is based on switching the functioning regimes of bistable gene networks, which can maintain the two alternative levels of gene expression under the same conditions. Cyclic digenic systems with negative feedback represent an example of a simple bistable gene network. Cells carrying artificial cyclic digenic systems on plasmids inherit each alternative phenotype upon exponential growth on rich medium during several cell generations. The action of specific inducers is necessary for switching. In this work, the impact of changes in cell cultivation conditions on the phenotypic composition of the clonal Escherichia coli cell population containing artificial cyclic digenic systems with negative feedback was studied. Phenotypes differ with respect to the expression level of marker proteins: beta galactosidase and GFP. Slow growth on a medium containing little-available carbon sources was shown to cause the transition from the phenotype Lac- to Lac+ in the absence of inducers. Phenotypic switching cannot be explained by transcriptional activation of the lactose operon, because 80 +/- 15% of cells inherit the acquired phenotype after replating bacteria on rich medium. Inheritance of the phenotype Lac- in batch culture depends on the medium and duration of cultivation. Dynamics of changes in the activity of beta-galactosidase and culture fluorescence suggests that a decrease in the level of metabolism resulted in the switch of these cyclic systems from bistable to monostable functioning regime, which corresponds to the Lac+ phenotype with respect to the ratio of regulatory proteins. Thus, the instability of growth conditions may cause phenotypic heterogeneity in the clonal population of cells containing bistable gene networks. PMID- 20583596 TI - [Involvement of the global regulators GrrS, RpoS, and SplIR in formation of biofilms in Serratia plymuthica]. AB - Most bacteria exist in the natural environment as biofilms, multicellular communities attached to hard surfaces. Biofilms have a characteristic architecture and are enclosed in the exopolymer matrix. Bacterial cells in biofilms are extremely resistant to antibacterial factors. It was shown in this work that the GrrA/GrrS system of global regulators of gene expression and the sigma S subunit of RNA polymerase (RpoS) play a significant role in positive regulation of biofilm formation in the rhizospheric bacterium Serratia plymuthica IC1270. Inactivation of grrS and rpoS genes resulted in an up to six-to-sevenfold and four-to-fivefold reduction in biofilm formation, respectively. Mutations in the grrS gene decreased the capacity of the bacterium for swarming motility. The splIR Quorum Sensing (QS) system was shown to negatively influence the biofilm formation. Transfer of the recombinant plasmid containing cloned genes splI/splR of S. plymuthica HRO-C48 into S. plymuthica IC1270 cells led to a twofold decrease of their ability to form biofilms. Inactivation of the splI gene coding for the synthase of N-acyl-homoserine lactones in S. plymuthica HRO-C48 resulted in a 2-2.5-fold increase in the level of biofilm formation, whereas the inclusion of plasmid carrying the cloned splI/splR genes into these mutant cells restored the biofilm formation to the normal level. The results obtained demonstrate that the formation of biofilms in S. plymuthica is positively regulated by the GrrA/GrrS and RpoS global regulators and is negatively regulated by the SplIR QS system. PMID- 20583597 TI - [Genetic variation of some varieties of common juniper Juniperus communis L. inferred from analysis of allozyme loci]. AB - Using the method of allozyme analysis, genetic variation, diversity, and population structure of Juniperus communis L. var. communis and J. communis L. var. saxatilis Pall. (= J. sibirica Burgsd. = J. nana Wild), growing on the territory of Russia, J. c. var. communis from Sweden, and J. c. var. depressa Pursh from Northern America (Alaska), was investigated. The total level of genetic variation of these varieties was found to be higher than the values obtained for the other conifers. The population samples of J. c. var. depressa from Alaska and J. c. var. saxatilis from Sakhalin were noticeably different from all other populations examined. Between the other samples, no substantial genetic differences were observed. These populations were characterized by weak interpopulation differentiation along with the absence of expressed geographical pattern of the allele frequency spatial distribution. The only exception was the procumbent form of common juniper from the high mountain populations of South and North Ural, which was somewhat different from the others. PMID- 20583598 TI - [Genetic variation of Oplopanax elatus (Nakai) Nakai (Araliaceae)]. AB - Using allozyme analysis, genetic and genotypic variation of rare relict species, a member of one of ancient angiosperm families, Araliaceae, the clone-forming plant Oplopanax elatus (Nakai) Nakai, was evaluated. Electrophoretic separation of the enzymes is described, and genetic interpretation of the enzymes variation patterns is presented. The values of genetic variation indices obtained were low (P = 25%; A = 1.45: Ho = 0.131; He = 0.113) and comparable with the data reported for the rare plant species and the representatives of the family Araliaceae. The main factors responsible for the polymorphism level observed might be the evolutionary history of the species and gene drift. The level of genotypic diversity (G/N = 0.76; D = 0.97) was substantially higher, compared to the values reported for species with vegetative reproduction (D = 0.62). These results suggest certain contribution of the propagation by seeds in the formation of the species of interest. PMID- 20583599 TI - [Genetic control of gliadin components in wheat Triticum spelta L]. AB - The componental composition of electrophoretic spectra of gliadin in Triticum spelta L. was studied. By analogy with common wheat T. aestivum L., it was established that genes controlling gliadin components in spelt are also located in short arms of chromosomes of homeological groups 1 and 6. Analysis of gliadin spectra in F2 grains from the crosses k-20539 x Ershovskaya 32 and k-20558 x Ershovskaya 32 revealed linkage of some components and their grouping into blocks (alleles) of coinherited gliadin components. Alleles of gliadin-coding loci identical to alleles of common wheat and new alleles earlier unknown for wheat populations have been identified. PMID- 20583600 TI - [Dynamics of chromosome variation in mole voles Ellobius tancrei (Mammalia, Rodentia) in Pamiro-Alai in the period from 1982 to 2008]. AB - Analysis of a new karyological material of mole voles Ellobius tancrei from a zone of high chromosome variation (Pamiro-Alai) in comparison with the data obtained 25 years ago showed a slight shift of the chromosome numbers on the western border of the Robertsonian fan due to the expansion of the area of forms with a low chromosome number. In the central part of the fan zone, the process of active hybridization of forms with different chromosome numbers, but not of the original forms, is still going on. Some problems of speciation on the basis of Robertsonian translocations are discussed. PMID- 20583601 TI - [Polymorphism of microsatellite markers in breeds of common carp (Cyprinus carpio L.) of Russian breeding]. AB - Using five microsatellite loci, genotyping and genetic diversity estimates were obtained for nine samples representing seven common carp breeds most widespread in Russia. For comparison, the samples of Amur wild common carp (Cyprinus carpio haematopterus) and a sample of European Hungarian common carp were used. In the samples examined (n = 148) a total of 78 alleles were revealed. The highest mean allele number per locus (4.3) was identified in Amur wild common carp, while the lowest number was found in Cherepets carps (4.0). In different breeds, the observed heterozygosities varied from 0.819 (Altai carp) to 0.651 (Cherepets scaly carp). Three out of five microsatellite loci (MFW-24, MFW-28, and MFW-19) revealed a high level of population differentiation. In the dendrogram of genetic differences, all breeds clustered into two groups. One of these groups was composed of the two strains of Ropsha common carp, Stavropol common carp, Amur wild common carp, and the two samples of Cherepets common carp. The second cluster included Altai common carp (Cis-Ob' and Chumysh populations), two Angelinskii common carp breeds (mirror and scaly), and Hungarian common carp. The pairs of breeds/populations/strains, having common origin, were differentiated. Specifically, these were two populations of Altai common carp, two strains of Ropsha common carp, as well as the breeds of Angelinskii and Cherepets common carps. The reasons for genetic differentiation of Russian common carp breeds, as well as the concordance of the evolutionary histories of these breeds, some of which originated from the European breeds, while the others contain substantial admixture of the Amur wild common carp, are discussed. PMID- 20583602 TI - [The expression of transmission ratio distortion (TRD) and the frequency of carriers of t haplotypes in natural populations of house mice Mus musculus]. AB - The character of TRD (transmission ratio distortion) was analyzed using the database formed on the basis of the results obtained for a collection of mice carrying different t haplotypes during 30 years of experimental observations. Quantitative TRD parameters were determined in male mice with T/t(w) genotypes from natural populations in crosses with females from laboratory collections. The TRD value varied in the range from 0.41 to 0.74. The frequencies of t haplotypes in natural Mus musculus populations from different regions (Moscow, Moscow oblast, Tajikistan, Lithuania, and Mongolia) varied from 12% (Tigrovaya Balka, Tajikistan) to 44% (Ulan-Bator, Mongolia). The factors and mechanisms determining a low frequency of t haplotypes in natural populations are discussed. PMID- 20583603 TI - [Genomic versus chromosomal polytypy in studies of mitochondrial and nuclear DNA markers in the Microtus arvalis group]. AB - Common voles of the Microtus arvalis group distributed over the territory of European Russia are represented by three karyotypic categories, i.e., sympatric sibling species with 2n = 46 and 54, and two allopatric karyoforms in one of them, 2n = 46. For each category, molecular markers were found. For two 46 chromosome forms (arvalis and obscurus), DNA was for the first time studied in karyotypes and non-karyotyped specimens for a parapatric hybrid zone, where high diversity of intermediate karyotypes was recorded. Preferential migration of the mitochondrial markers in arvalis and significant differences in the cline width for chromosomal and nuclear markers in obscurus were shown. The hybrid zone examined exhibited unusual combination of such features as the practically complete absence of "pure" representatives of the original parental forms and a clear deficiency of the first generation hybrids. The mtDNA divergence for the arvalis and obscurus karyogroups (4.6%) is comparable to the lowest limit for interspecies differences within the large and complex genus Microtus. PMID- 20583604 TI - [Polymorphism of a short fragment of the mitochondrial genome control region (D loop) in the Siberian roe deer Capreolus pygargus Pallas, 1771 (Artiodactyla, Cervidae) from the Russian Far East]. AB - Genetic diversity of Siberian roe deer Capreolus pygargus, 1771 from the Russian Far East was studied based on polymorphism analysis of a mtDNA control region fragment (390 bp). Three phylogenetic lines were found in the animals examined. The trend for change of haplotypes of different phylogroups was shown to occur from north to south in Sikhote-Alin. The haplotype distribution of Siberian roe deer in the Russian Far East correlated with data on morphologiocal variability. PMID- 20583605 TI - Biogeographic study of the honey bee (Apis mellifera L.) from Serbia, Bosnia and Herzegovina and Republic of Macedonia based on mitochondrial DNA analyses. AB - In this work, Apis mellifera carnica and A. m. macedonica honey bees from Serbia, Bosnia and Herzegovina and Republic of Macedonia were analysed using molecular techniques in order to improve our knowledge about biogeography of A. mellifera on the Balkan peninsula. This is the first time that the indigenous honey bees from Bosnia and Herzegovina and Republic of Macedonia have been analyzed using a molecular approach. Sampling was carried out from 560 stationary apiaries where bees were kept in traditional hives (woven skeps). The COI-COII regions of 1680 samples were PCR-amplified and sequenced. To reveal the haplotype of studied bees, the obtained sequences were aligned with published sequence data of haplotypes that belong to A. mellifera C phylogenetic lineage. The C2D mtDNA haplotype was found in all honey bees sampled from Serbia, Bosnia and Herzegovina and Republic of Macedonia. These results show that A. m. carnica and A. m. macedonica share the same C2D mtDNA haplotype. COI gene segments of 1680 samples were PCR-amplified and digested with restriction enzymes NcoI and StyI in order to discriminate A. m. macedonica from A. m. carnica. Amplified fragment patterns produced by both restriction enzymes matched with diagnostic pattern characteristic for A. m. macedonica in case of samples from east, south and south west parts of Serbia, and Republic of Macedonia, fragments of samples from northern part of Serbia and Bosnia and Herzegovina did not include NcoI and StyI restriction sites. These results indicate that honey bees from east, south and south-west parts of Serbia, and Republic of Macedonia belong to the A. m. macedonica, and honey bees from northern part of Serbia and Bosnia and Herzegovina belong to another subspecies, probably to the A. m. carnica. Therefore A. m. macedonica has much wider area of distribution than it was previously considered. PMID- 20583606 TI - [Marriage structure of Yakut populations: migrations]. AB - Rural and urban settlements of the Republic of Sakha (Yakutia) are characterized by intense marriage migrations: both indigenous residents of different uluses (districts) of the republic (7-30%) and migrants from outside Yakutia (7-29%) contract marriages in five administrative centers analyzed in this respect. All the populations studied are characterized by a wide geographic range of the birthplaces of persons contracted marriages there (from 14 to 24 uluses of Yakutia), without any predominant migration flow from one district to another. The proportion of homolocal marriages among indigenous ethnic groups (Evenks, Evens, and Yukagirs) is as high as 75-100%; this proportion among Yakuts varies from 26 to 68%; heterolocal marriages are more characteristic of Russian immigrants (41-95%). Positive assortative marriages among persons with the same birthplaces have been found in all populations except for Momsky ulus. PMID- 20583607 TI - [Mutation analysis of K-ras protooncogene in colorectal adenocarcinomas and polyps in Russian patients]. AB - To estimate diagnostic value of K-ras mutations during cancer risk group formation, they were studied in the samples of sporadic carcinomas (n = 33) and malignant (n = 13) polyps of large intestine obtained during surgery or polypectomy. Using PCR analysis, restriction analysis, SSCP analysis and automated sequencing, eight various point mutations were revealed. Six of them were located in codon 12 and two, in codon 13 of the K-ras gene. Mutation frequency in carcinomas, benign and malignant polyps was 43, 49, and 69%, respectively. In the healthy tissue of the large intestine, no changes in codons 12 and 13 in the K-ras gene were observed. Mutations in the groups of Russian patients examined partially overlapped. In patients with colorectal carcinoma the mutation frequency in the K-ras gene was not associated with disease onset age, location, and the extent of tumor differentiation while it was associated with the stage of tumor process. The maximum mutation frequency was revealed in polyps of patients over 70 years of age as well as in the adenomas of villous histology and large size ((1 cm). No correlation between the K-ras mutation frequency and the extent of polyp dysplasia was observed. PMID- 20583608 TI - [Barrai's parameters for the Kirov oblast population and their geographic distribution]. AB - The distribution of surnames in for populations of the district rank in Kirov oblast has been used to calculate Barrai's parameters, which are the following: Ir, 0.0008-0.0208; H, 6.80-11.57; v, 0.003-0.058; alpha, 47.35-1191.39; R, 23.03 50.07. The results have been compared with data on the 1980s; no substantial changes in the studied parameters during a generation have been found. PMID- 20583609 TI - [Molecular structure of the allelic variants of (AAT)n microsatellite locus Du47D in the parthenogenetic species Darevskia unisexualis and bisexual parental species D. valentini and D. raddei]. AB - Microsatellite repeats are one of the most widespread elements of the eukaryotic genome, but are poorly studied in species with clonal reproduction. PCR analysis and DNA sequencing were used to study the molecular structure of the allelic variants of microsatellite locus Du47D in the parthenogenetic species Darevskia unisexualis and its evolutionary ancestors, bisexual species D. raddei and D. valentini, of the genus Darevskia (Lacerta saxicola complex). Sequencing showed that the allelic variants of the D. unisexualis Du47D locus and the alleles of its D. raddei and D. valentini orthologs have a perfect microsatellite cluster structure, differ in number of ATT monomeric units, and have certain species specific combinations of nucleotide substitutions, deletions, and insertions in the microsatellite-flanking DNA sequences. The Du47D alleles that the parthenogenetic species inherited from D. valentini or from D. raddei were identified. PMID- 20583610 TI - [The retinal pigment epithelial cells of the adult newt and rat under conditions of in vitro organotypic culture]. AB - To understand why the retinal pigment epithelium (RPE) has different potentials for neural differentiation in lower and higher vertebrates, the RPEs of adult newts and rats were compared under similar in vitro cultivation conditions. The RPEs of both animal species were organotypically cultivated within the posterior eye wall under constant rotation in the serum medium free of growth factors. Comparison of the cell morphology, proliferation, and expression of pan-neural markers demonstrated that the RPE cells of adult newts and rats under similar in vitro conditions displayed both similarities and differemces. They were able to synthesize DNA but rarely divided mitotically. In addition, part of the RPE cells of both the newt and the rat were dislodged from the layer, migrated, and acquired a macrophage phenotype. However, the majority of the cells retained the initial morphology and remained within the layer. In several cases, these cells displayed the initial characteristics of neural differentiation, namely, expression of pan-neural proteins. The difference between the newt and rat RPE cells was in the ability of the former to generate in vitro an additional row of dedifferentiated NF-200-positive cells, characteristic of in vivo newt retinal regeneration. These data demonstrate that the RPE cells of the adult newt and rat retain the potential of manifesting neural cell traits; however, more advanced changes towards differentiation are characteristic of only the newt RPE. PMID- 20583611 TI - [Transcriptional factor Pitx2: localization during triton retina regeneration]. AB - For the first time immune-chemical analysis of transcriptional factor Pitx2 localization during triton retina regeneration after its removal and also in tissues of a nonoperated eye of an adult triton has been carried out. Protein Pitx2 has been found in the nucleus of the earliest neuroblasts that form the germ of the retina. At a later stage of retina regeneration, Pitx2 was found in the nucleus of differentiating cells of ganglionic layers that correspond to Pitx2 protein localization in the native retina. Protein Ptix2 has also been found in the nucleus of less differentiated cells of the peripheral region of regenerative and native retina. It was demonstrated that protein Pitx2 is expressed not only in retina but also in other tissues of the posterior sector of the eye (pigment epithelium, choroid) using immune-histochemical and Western blot hybridization. It is supposed that transcriptional factor Pitx2 has been involved in the control of subsequent stages of retina regeneration from pigment epithelium cells. PMID- 20583612 TI - [The correlation between fish growth and several biochemical characteristics by the example of the steelhead Parasalmo mykiss Walb]. AB - Correlation analysis demonstrated a statistically significant correlation of linear-weight characteristics of the steelhead rainbow trout (cultivated steelhead form) with an RNA/DNA ratio and the expression level of the gene encoding cytochrome c oxidase (CO) in two-year-old individuals (1+) as well as the expression level of the gene encoding the myosin heavy chain (MyHC) and activities of the enzymes CO and lactate dehydrogenase (LDH) in muscles and 1 glycerophosphate dehydrogenase (1-GPDH) and glucose-6-phosphate dehydrogenase (G 6-PDH) in the liver of two- and three-year-old individuals (1+ and 2+). With age, the correlation of 1-GPDH and G-6-PDH activities in the rainbow trout liver with the fish body weight increased, whereas their correlations with the body length reduced. The age- and sex-related distinctions in the MyHC gene expression and activities of the white muscle enzyme LDH and the liver enzymes 2-GPDH and G-6 PDH were detected in rainbow trout of both age cohorts. PMID- 20583613 TI - [Variability of the exogenic antioxidant effect on survival: modeling in Drosophila lines with different lifespan and l(2)gl-tumor suppressor dosage]. AB - Different exogenic antioxidants and geroprotectors are used to decrease age abnormalities and enhance the human life span. However, the antioxidant effect on lifespan is variable and requires detailed analysis. In the present report, we modeled in Drosophila the peculiar character of action of various doses of a new phenol antioxidant TC-13. We studied the TC-13 effect on aging of two Drosophila lines with genetically determined contrast lifespan dynamics. In addition, we tested the TC-13 antioxidant influence on the background of heterozygozity on the loss-of-function mutation of the l(2)gl tumor suppressor. The differing effect of TS-13 on LS, the character of which depends on the antioxidant dosage, genotype of line, and sex of Drosophila, was found. TS-13 in the concentration 0.2% did not affect the lifespan in all studied lines and decreased survival, whereas the antioxidant in a concentration of 1% positively affected the lifespan in both males and females of long-living lines. The antioxidant effect on animal lines with a smaller dose of tumor suppressor l(2)gl resulted in a decrease of the lifespan. PMID- 20583614 TI - [Fungal to bacterial biomass ratio in the forest soil profile]. AB - The carbon content in microbial biomass (Cmic-BM) was determined in various horizons of the soil profile (sod-podzo, gray, podzol, and rzhavozem) of various forests (oak, spruce Yellow Archangel, spruce moss, aspen, spruce broadleaf) in the southern taiga of European Russia (Moscow and Kaluga oblasts) by the substrate induced respiration (SIR) and direct microscopy (DM) methods. The fungi to-bacteria ratio was measured by the selective inhibition technique and DM. A quantitative differentiation of the fungal mycelium was suggested. The Cmic DM/Cmic-SIR in various horizons of the soil profile was about 98%. The fungal contribution to MB was 52-74% and 92-99% according to the SIR and DM data, respectively. The microbial parameters were associated with the CO2 and N2O production by the soils. The contradictory data about the fungi proportion in the MB of soils of various ecosystems were discussed. PMID- 20583615 TI - [Transition of entheropathogenic and saprotrophic bacteria in the eco-niche cycle: animals-excrement-soil-plants-animals]. AB - The possibility of transition of saprotrophic and enteropathohenic bacterial populations following the chain of naturally related habitats--fodder-animal gastrointestinal tract (GIT)-animals excrement-soil-plants and again animals with a cyclic formation--has been investigated quantitatively. All bacteria used in the experiments have been shown to successfully overcome all the mechanical, physical-chemical, and biological barriers in the food chain and to come out into the environment with a quite high number. It has been demonstrated that the same bacterial population can pass the whole cycle without additional introduction of similar populations from the outside. PMID- 20583616 TI - [Role of differential expression of sdh1-1 and sdh1-2 genes in alteration of isoenzyme composition of succinate dehydrogenase in germinating maize seeds]. AB - A probable mechanism of alteration of the isoenzyme composition of succinate dehydrogenase (SDH) due to differential expression of genes encoding subunit A was considered. The alteration of SDH activity during maize seed germination was investigated, and its maximal activity on day 4-5 of germination was found. The alteration of the sdh1-1 and sdh1-2 gene expression level during maize seed germination was evaluated using the quantitative polymerase chain reaction method. The presence of four forms of the studied enzymes, providing multiple SDH functions was found in maize inflorescence using electrophoresis in polyacrylamide gel. PMID- 20583617 TI - [Structure of the glial cells in the nervous system of parasitic and free-living flatworms]. AB - This study is devoted to ultrastructural and immunosytochemical investigation of the nervous system in parasitic and free-living platyhelminthes to learn if glial cells exist in the nervous system of flatworms. We described the ultrastructure of different types of glial cells and the peculiarities of myelinization of gigantic axons; immunoreactivity to the S100b protein is revealed. Comparative analysis of the glia structure of annelids and platods is given; structural, functional, and evolutionary aspects of myelinization of gigantic axons, which are revealed in cestodes, are discussed. PMID- 20583618 TI - [The spatial organization of winter bird communities in the East European and West Siberian plains]. AB - The main trends in the territorial changes in winter bird communities and the environmental factors determining them were analyzed based on long-term counts in the East European and West Siberian plains. These trends are reduced to a decline in the winter avian complexes (in the number of species and individuals) in the north- and eastward directions and with a decrease in the degree of sheltering and feed reserves in the habitats associated with reduction in afforestation. The specific regional features of winter East European avian complexes are the larger number of species and individuals in the nemoral forest, forest-steppe, and steppe landscapes, and inland water bodies as compared with the West Siberian avian complexes, as well as an increased influence of the degree of development and agricultural transformation of landscapes. PMID- 20583619 TI - [Coordination between locomotor and respiratory rhythms in the great ramshorn snail Planorbarius corneus: transmitter-dependent modifications]. AB - In a reduced preparation of Planorbarius corneus consisting of the CNS and mantle complex, both the dopamine precursor L-DOPA and the serotonin precursor 5-HTP have been found to be able to induce and maintain rhythmic pneumostome (PN) movements phase-coupled to fictive cyclic locomotion in a neurotransmitter specific manner. After the transection of pedal commissures, pharmacologically induced PN movements were coordinated with the locomotor activity rhythm generated by the left pedal ganglion, as in Lymnaea regardless of spatial inversion of its CNS. Nevertheless, in Planorbarius during the 5-HTP-induced fictive muscular locomotion, the PN was never opened, but cuddled up to the mantle at the same phase of the locomotor cycle corresponding to close down the PN in Lymnaea. PMID- 20583620 TI - [Effect of rabbit adaptation to cold on the depressor muscarinic cholinergic reaction of the arterial pressure of the hind limb vessels and the small intestine in situ and the systemic arterial pressure]. AB - Modification of the main parameters of cholinergic reactions in rabbits, i.e., of the specific sensitivity to agonists (EC50), maximal reaction values (Pm) of arterial pressure in the hind limb vessels and small intestine in situ, and systemic arterial pressure after adaptation to cold for 1, 5, 10, and 30 days has been investigated. The depressor reaction to acetylcholine (muscarinic cholinergic receptors agonist) was established to correspond to the model p = (PmAn)/(EC(50)(n) + An) with n=1. In the control EC50 was equal to 0.85, 1.01, and 1.21 nmol/kg, while Pm equaled 100, 32.6, and 61.2 mm Hg for the hind limb vessels, small intestine in situ, and systemic arterial pressure, respectively. As a result of rabbits adaptation to cold in situ, qualitatively similar modifications in the EC50 and Pm value in the hind limb vessels and in the small intestine occurred with correlation coefficient r = 0.83 for the EC50 parameters and r = 0.74 for the Pm parameters. No correlations between EC50 and Pm in the systemic arterial pressure were observed. PMID- 20583621 TI - [Influence of derivatives of arachidonic and docosohexaenic acids on AMPA receptors in Purkinje neurons and cognitive functions in mice]. AB - The effect of derivatives of arachidonic and docosahexaenoic acids on AMPA receptors in Purkinje cells from the rat cerebellum was studied using the patch clamp electrophysiological method. It was shown that derivatives of arachidonic acid-arachidonoyl dopamine and docosahexaenoic acid-docosahexaenoyl dopamine and ester of docosahexaenoic acid with ethylene glycol in nanomolar concentrations effectively potentiated the ionic currents caused by activation of AMPA receptors of kainic acid. Ester of docosahexaenoic acid with nitroethylene glycol blocked AMPA receptors, and anandamide (ethanolamide of arachidonic acid) was not effective. A behavioral test showed that docosahexaenoyl dopamine in doses of 0.1 20 mg/kg had no effect on the learning and memory abilities of the animals tested. PMID- 20583622 TI - [Fibrinolytic and hypoglycemic effects of the Pro-Gly-Pro-Leu peptide during development of insulin-dependent diabetes in rats]. AB - Repeated (over 7 days) intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals at a dose of 1 mg/kg before injection of the diabetogenic metabolite alloxan provided effective protection of an organism against development of insulin-dependent diabetes mellitus and prevented development of hypercoagulating alterations in the system of hemostasis. An increasing in the anticoagulating and fibrinolytic activities in rat blood plasma was detected. The peptide under study also showed antidiabetogenic action: repeated intranasal introduction of the Pro Gly-Pro-Leu peptide into animals for 7 days inhibited development of diabetes symptoms in rats pretreated with alloxan. PMID- 20583623 TI - [Spatial distribution of Marmota baibacina and M. sibirica (Marmota, Sciuridae, Rodentia) in a zone of sympatry in Mongolian Altai: bioacoustic analysis]. AB - The spatial distribution of two marmot species Marmota baibacina and M. sibirica in a zone of coexistence was studied by using their alarm call as a diagnostic trait. It was found that M. baibacina prefers to inhabit bouldery screes, whereas M. sibirica inhabits all suitable biotopes. The difference in biotopic distribution of these species could be explained by M. sibirica forcing M. baibacina out of optimum habitats. Cases of coexistence of both species in one family group sites were registered, which might contribute to the appearance of hybrids. PMID- 20583624 TI - [Volutionary reorganizations of ontogenesis in related frog species of the family Myobatrachidae]. AB - Literary data on the comparative embryology of Australian endemic frogs of the family Myobatrachidae have been considered. Six main types of development have been recognized, the important criteria for which are egg size, the site of embryo and tadpole development (in water or on land), the character of larval nutrition (exotrophic or endotrophic), the occurrence of direct development, brooding, etc. An attention has been also paid to the character of the early cleavage process in the embryos of various species. The peculiarities of ontogeny in Myobatrachidae are compared with those in representatives of other families in the order Anura. The perspectives of some further embryological studies of this Australian frog family have been outlined. PMID- 20583625 TI - [Geometry and mechanics of the morphogenesis of active membranes on the example of plant trichome cells of the genus Draba L]. AB - The stages of the early morphogenesis of simple (unbranched) and complex (branched) unicellular trichomes are studied in two species of the genus Draba- D. sibirica (Pall.) Thell. and D. daurica DC. The geometry of morphogenesis is estimated by analyzing intraindividual variation of quantitative morphological characteristics of the developing leaf blade and peduncle trichomes. The surface of all types oftrichome cells first acquires a spherical shape, followed by a U shaped configuration with cylindrical proximal and spherical distal regions. In the development of complex trichomes, the area of the distal zone grows at a higher rate, which leads to separation of its volume into individual spherical regions, the morphogenesis of which repeats the early morphogenetic stages of the overall trichome cell, forming simple (unbranched) or complex (branched) trichome rays. As a rule, the lateral polarity of a trichome cell coincides with the proximodistal polarity of the leaf. Quantitative morphological data make it possible to infer an algorithm of the changes in shape common for all trichome cells, namely, the growth cycle comprising alternation of the phases of increase and decrease in the curvature of the outer cell surface. This surface is an active membrane expanded by the internal pressure and concurrently capable of actively increasing its area by incorporation of new structural elements. A distinctive feature of the proposed model is the geometrical inhomogeneity of the surface movement, changing the radius of curvature and creating internal (active) mechanical stresses in this membrane. A decrease in the ratio of the membrane surface area to the volume deprives the spatially homogeneous shape of its stability; correspondingly, the transition from elastic resistance to internal pressure to active resistance with the help of curvature differentiation becomes more energetically favorable. The source for growth and morphogenesis of the active membrane is alternation of the phases of local curvature leveling, which "charges" the membrane with active mechanical stresses and "discharge" of these stresses, leading to differentiation of the membrane's local curvatures. PMID- 20583626 TI - [Changes in topology and geometry of the embryonic epithelium of Xenopus during relaxation of mechanical tension]. AB - The paper presents the results of statistical evaluation of the changes of cellular apex connections, apical angles, and apical indices of ventral cells of the epiectodermal gastrula of Xenopus during the first HC-four hours after the relaxation of mechanical tension. In the unrelaxed epithelium, an overwhelming majority of cells have three apical connections, apical angles close to 120 degrees, and apical indices around one (isodiametric cells); after relaxation, the number of cells with more than three connections, the number of apical angles deviating substantially from 120 degrees, and the percentage of columnar cells with high apical index increase. Apices with more than three connections tend to gather in enclosed groups, forming a smooth line of cell walls. The length and curvature of cell walls with four apical connections significantly exceeds those same indicators for cells with three apical connections. The observed changes in topology and geometry of cells correspond to reconstructions observed during normal morphogenesis. They are considered in terms of the hyper-restoration model of mechanical tension in relaxed epithelial layers. PMID- 20583627 TI - [Docosahexaenoyl dopamine in freshwater hydra: effects on regeneration and metabolic changes]. AB - The effects of docosahexaenoyl dopamine and docosahexaenoic acid on the regeneration of hydra gastric and basal fragments are studied. Docosahexaenoyl dopamine induced morphogenetic abnormalities such as single ectopic tentacles in the gastric region and projections in the gastric and basal regions. Docosahexaenoic acid had no effect on the morphogenesis except for a mild slowing of the regeneration rate. Since no hydrolysis of docosahexaenoyl dopamine was detected in hydra extract, it was assumed that the morphogenetic effect could be associated with the dopamine component of this complex. PMID- 20583628 TI - [Disproportionate eruption of maxillary and mandibular incisors in the long tailed ground squirrel]. AB - Abstract-The surface of the maxillary and mandibular incisors of Spermophilus undulatus long-tailed ground squirrels, including those born in the current year and those that have hibernated (trapped one month or later after hibernation) is studied. The presence of daily growth on the incisors' surface allows the evaluation of their eruption rate; a specific change in the character of the incisors' eruption corresponds to winter hibernation (hibernation zone), which serves as the time mark. Correlation between the eruption rates of the maxillary and mandibular incisors typical for rodents is found in yearlings and some animals after hibernation. The eruption rate of the mandibular incisors is higher than the eruption rate of the maxillary incisors and can be taken as proportional to their length. In individuals that have hibernated and show proportional eruption of the incisors, the proportion of the total length of the incisor formed before and after hibernation is equal for the maxillary and mandibular incisors. In the individuals that have hibernated and show the correlation of the total length of the maxillary and mandibular incisors typical for rodents, the eruption rate of the mandibular incisor is equal to or less than the eruption rate of the maxillary incisor and the proportion of the incisor formed before hibernation is greater in the mandibular incisor than in the maxillary. This disproportionate pattern of incisor eruption is not typical for rodents and is a result of inequal grinding of the maxillary and mandibular incisors, which ultimately results in the normal ratio of the total length of the maxillary and mandibular incisors. PMID- 20583629 TI - [Interlinear differences in generative function formation in pubescence of male mice]. AB - The formation of generative function in pubescence is studied in males of three inbred mice lines BALB/cLac, CBA/Lac, and PT. From days 35 through 60 of life every 5 days the amount of sperm cells and the quantity of abnormal heads of spermatozoa in males are calculated in both epididymises and the morphometry of the testicles, epididymises, and seminal vesicles is carried out. Interlinear deviations in the pubertal dynamics of the parameters of spermatogenesis and the morphometric indexes are determined, indicating a weak spermatogenesis process in males of CBA/Lac in comparison with males from the other lines. Males from the line CBA/Lac are characterized by a low amount ofepididymal spermatozoa combined with low frequency of abnormal spermatozoon heads; these traits can be considered as a compensatory process that increases fertility, By the end of the period, i.e., on days 55-60 of life, the males of all three inbred mice lines have not reached the definitive level in the number ofepididymal spermatozoa; the weight of the testicles, epididymise, and seminal vesicles; and body weight. Thus, in laboratory mice, the beginning of reproductive activity is not connected with these reproductive indexes reaching the definitive level. The results of the study show that in adult mature males of laboratory mice the interlinear deviations in generative function emerge in the pubertal period and persist thereafter. PMID- 20583630 TI - [Polyunsaturated fatty acids prevent the development of locomotor disturbances caused by changes in the neurohumoral background in rat pups]. AB - The present study shows the effectiveness of using polyunsaturated fatty acids in pregnant rats in order to prevent behavioral alterations in neonatal rats caused by the action of the pathogenic peptide factors of blood serum with perinatal damage of the central nervous system. PMID- 20583631 TI - [Cytogenetic study on the activity of the ferret embryonic genome before implantation]. AB - A cytogenetic study of the activity of the embryonic genome in ferret (Mustelaputorius) blastocysts during 6 days after their transition from the oviduct to the uterus has been carried out. It has been found that the prolongation in the preimplantation period in the ferret is not accompanied by inhibition of mitosis or activity in nucleolus organizing regions of inner cell mass cells as occurs in species having an obligatory delay of implantation (obligate embryonic diapause). Amitosis of trophoblast cells starts at the periimplantation stage as in other species that do not have obligate diapause. The data obtained are consistent with the hypothesis that the obligatory stage of delayed implantation might occur in some mammals in different taxonomic groups as a result of chromosome mutations affecting the genetic control of the chronology of events (timing) of embryogenesis. Consequently the characteristics of delayed implantation should be different in different species. PMID- 20583632 TI - [Nursing father--myth or reality? The role of secretions of father-male specific skin glands in survival and of Campbell's hamsters offspring (Phodopus campbelli Thomas, 1905; Cricetidae, Rodentia)]. AB - Biparental Campbell's hamster (Phodopus campbelli) were used for testing the hypothesis that secretions of father-male specific skin glands (midventral gland and additional sacculi) may promote juveniles survival in mother's absence. For the hypothesis testing, juveniles at age 7 or 8 days were left either with father or with mother till day 30, and their survival and growth rate were compared. Amongst males, there were 26 surgically operated specimens (with midventral gland and sacculi removed, group OP, rearing 128 juveniles) and 37 sham operated specimens (group SHAM, rearing 189 juveniles). Control group (where both parents were intact and present) consisted of 28 pairs with 166 juveniles. Separation from female-mother led to significant decrease in pups body weight during first days of experiment; this effect was more pronounced in OP group. The majority of OP pups (92.3% and 52.6% of those separated from mothers on 7th and 8th day, respectively) were to be returned to females due to emaciation threatening their lives ("lost"). In SHAM group the amount of "lost" pups was significantly lower (43.5 and 21.6% respectively, P < 0.001). The data obtained suggest that activity of father-male specific skin glands may be an important factor determining pups survival and growth. Apparently, the glands secretion can be a reserve source of nutritive material for deserted juveniles. PMID- 20583633 TI - [Structure and geography of hydrothermal communities in the Global ocean]. AB - Hydrothermal vent communities in different regions have been explored using deep sea manned submersibles "Pisces" and "Mir". Microdistribution of dominating animals has been studied by means of visual observations, photo and video analyses. In the present work, a generalized scheme of vent field zonation is proposed/based on microdistribution patterns of vent organisms in different regions. In disjunct biogeographic regions, established zones are marked by vicariating taxa and assemblages. Most previous biogeographic studies address the distribution of vent taxa. In our study we attempt to reveal general patterns of hydrothermal assemblages and communities distribution. Therefore we address the distribution of leading species dominating or codominating vent assemblages. According to the analysis, eight main biogeographic regions can be established in the Pacific, Atlantic, and Indian Oceans. Communities in disjunctive biogeographic regions are clearly distinguished, first of all, by the dominance of different taxa in the euthermal (near-went or "shimmering water") zone. The analysis of vertical distribution of leading vent species reveals the most significant changes in community composition at the depths of 400-600, 1000-1500 and 2700-3000 m. It is concluded that geographic and bathymetric distribution patterns of vent communities demonstrate good concurrence with global-scale geographic and vertical distribution patterns of "normal" non-vent fauna. PMID- 20583634 TI - [Evolutionary basis of ecological diversity in dicotyledons]. AB - Evolutionary prerequisites of dicots current ecological diversity are studied. Structural and functional differences of the taxa generations replacing one another under the influence of the planet climate changes are described. The results of comparison of plant groups belonging to different subclasses confirm the adaptive parallelism in the structural and functional evolution, as well as the relationship between adaptogenesis and climate changes in Cenozoic. The supposition is made that the system of structural and functional traits of a taxon forms in compliance with climate specificity at the time and place of its establishment. Stability of plant species characters and their environmental requirements is corroborated by shift of species ranges in full accordance with habitat drift under climate changes influence. The similarity of evolutional and zonal series of dicots is shown. The present structural and functional diversity of taxa and ecosystems is considered to be a consequence of dissimilarity in their phylogenetic age. The conclusion is made that the current biological diversity is founded on historical diversity of habitats and plant species being phylogenetically adapted to them. PMID- 20583635 TI - [Convergent development of the subcutaneous muscles in moles and golden moles]. AB - The goal of the investigation was to clarify the ways of subcutaneous muscles development in burrowing forms of insectivores--moles (Talpidae) and golden moles (Chrysochloridae). To achieve the goal the comparative morpho-functional analysis of subcutaneous and facial musculature of six mole genera (Neurotrichus, Urotrichus, Talpa, Mogera, Scalopus, Parascalops), two genera of chrysochlorids (Chrysochloris, Eremitalpa), and some other non-specialized forms of insectivorous mammals from Erinaceidae, Tenrecidae, Soricidae and Solenodontidae was carried out. It was shown that some of m. cutaneus trunci derivatives interact intimately with facial musculature. Besides, subcutaneous muscle forms additional layers that facilitate the operation of shaking ground particles off the for, which is rather important for burrowers. Overall complication of subcutaneous musculature in moles and chrysochlorids is accompanied by convergent similarity in the development of some musculature portions. At the same time some layers of m. cutaneus trunci seem to have evolved in different, special ways. PMID- 20583637 TI - Keep the baby in the bathwater. PMID- 20583636 TI - [Nonparametric methods for comparative assessment of species diversity as applied to riverine macrozoobenthic communities]. AB - Models for relationship between sampling effort and estimates of species number and other characteristics of species diversity are considered and evaluated. In the analysis, different randomization algorithms and other statistical methods of monitoring data processing are used including jackknife and bootstrap procedures, algorithms ICE and Chao2, Colwell-Mao interpolation model, Mikhaelis-Menten curves, and others. A comparative analysis of overall species richness in macrozoobenthic communities using streams of the Lower Volga basin as a case study is performed with the aid of different extrapolation models, and the resulting estimates are discussed. The relationships are analyzed between sampling effort (number of hydrobiological samples) and cumulative estimates of species richness and basic indices of species diversity. The means towards improvement of conclusions substantiation when ranking riverine communities by species diversity are considered. PMID- 20583638 TI - Video conferencing used to provide care and support for hard to reach communities. PMID- 20583639 TI - A father's story. PMID- 20583640 TI - Interprofessional working through the eating abroad together project. AB - This article explores a collaboration between the health, social care and education faculties at Canterbury Christ Church University in the UK to address the Labour government's aims to promote healthy eating, language learning and cultural awareness in children, and collaborative working among professionals. The Eating Abroad Together project used healthy eating as a vehicle to promote the acquisition of language skills and the exchange of cultural experiences. It also promoted cross-curricular working between children's nursing students and student teachers in primary schools. PMID- 20583641 TI - Identifying medication errors in surgical prescription charts. AB - BACKGROUND: Each year 200 million prescriptions for children and adolescents are issued in the UK, with a 1.5 per cent prevalence of errors. AIM: To identify and quantify medication errors on surgical children's prescription charts over a four month period at two hospital sites. METHOD: Retrospective review of the prescription charts of 175 children at a children's hospital and a children's unit. RESULTS: Errors totalled 301, the most common was overwriting of a prescription, the least common was incorrect dates. No resulting adverse events were recorded. CONCLUSION: The prevalence of errors needs to be reduced to avoid serious adverse incidents. Computerised physician order entry systems are discussed as a potential solution. PMID- 20583642 TI - Techniques to use when consulting families about child health services. AB - Government policy proposed by Lord Darzi (2009) and others has highlighted the importance of consultation with patients and carers. NHS foundation trusts have a duty to consult local populations of patients, and these include children and their parents. In this article suggestions are made about how such consultation can be demonstrated by children's nurses. It outlines three techniques that nurses can use: patient stories, cafe scientifique and spotlight sessions. PMID- 20583643 TI - Nurses' roles in NHS reform. PMID- 20583644 TI - Involvement of private sector can save nurses time to care. PMID- 20583645 TI - College votes for directors of nursing to replace general managers. PMID- 20583646 TI - No more heroes. PMID- 20583647 TI - High impact actions: discharge planning. AB - This article, the first in a series on the NHS Institute for Innovation and Improvement's eight high impact actions, presents three case studies of how senior nurses in acute and community settings have developed hospital discharge arrangements to improve patient flow and ensure more effective use of bed capacity. PMID- 20583648 TI - Legal responsibility and accountability. AB - Shifting boundaries in healthcare roles have led to anxiety among some nurses about their legal responsibilities and accountabilities. This is partly because of a lack of education about legal principles that underpin healthcare delivery. This article explains the law in terms of standards of care, duty of care, vicarious liability and indemnity insurance. PMID- 20583649 TI - Changing your focus to achieve your goals. AB - To achieve their goals, nurses must be able to visualise and plan for them. This article, the second in a series of six, explains how changes in focus can lead to success. PMID- 20583650 TI - Workload and workforce planning: devolving the programme. AB - This article describes how implementing the Nursing and Midwifery Workload and Workforce Planning programme has been devolved from central government to individual NHS boards, and how its implementation has helped to ensure that senior nursing staff have become aware of their accountability for workload and workforce planning. PMID- 20583651 TI - Achieving quality assurance through clinical audit. AB - Audit is a crucial component of improvements to the quality of patient care. Clinical audits are undertaken to help ensure that patients can be given safe, reliable and dignified care, and to encourage them to self-direct their recovery. Such audits are undertaken also to help reduce lengths of patient stay in hospital, readmission rates and delays in discharge. This article describes the stages of clinical audit and the support required to achieve organisational core values. PMID- 20583652 TI - Embracing diversity. PMID- 20583653 TI - Lasting menace. PMID- 20583654 TI - Our inner Neandertal. PMID- 20583655 TI - Damp rocks from space. PMID- 20583656 TI - Microscopic giants. PMID- 20583657 TI - Putting addiction to bed. PMID- 20583658 TI - Heartburn headache. PMID- 20583660 TI - Patent still pending. PMID- 20583659 TI - Manipulation of the crowd. PMID- 20583661 TI - Terminate the terminators. PMID- 20583662 TI - Get serious about budget deficits. PMID- 20583663 TI - When scientists sin. PMID- 20583665 TI - Is the universe leaking energy? PMID- 20583664 TI - No country is an island. PMID- 20583667 TI - The dirty truth about plug-in hybrids. PMID- 20583666 TI - DNA drugs come of age. PMID- 20583668 TI - War of the machines. PMID- 20583669 TI - Clean energy from filthy water. PMID- 20583670 TI - Winged victory. PMID- 20583671 TI - How babies think. PMID- 20583672 TI - The drillers are coming. PMID- 20583673 TI - A new discipline in medicine, physiatry: physical medicine and rehabilitation. AB - Physiatry is a relatively new area of medicine worldwide and continues to evolve to meet the medical needs of patients. The fundamental goal of Rehabilitation Medicine is functional performance and quality of life. Lord Viscount Tedder stated, "that the greatest field of the specialty lay in the restoration of individuals to full physical fitness, for he said, "life was not merely to be alive, but to be well". One of the highest awards in the AAPMR is the Frank H Krusen Award, and one of the awardees, Henry Betts and Joel Press, the founder of the Spine and Sports Rehabilitation Center at the Rehabilitation Institute of Chicago, say, "Medicine adds years to people's life, Physiatry adds quality to those years." PMID- 20583674 TI - Early electron transfer in cytochrome c oxidase occurs by a chymotrypsin type relay. AB - Evidence suggests that when ferrocytochrome c (the substrate) reduces cytochrome c oxidase (COX), electrons from the former enter the latter via Trp-104. What is still to be determined is the method by which electrons are transferred from ferrocytochrome c to Trp-104 and the method by which electrons arriving at Trp 104 are moved on to Cu(A), the first of the enzyme's four redox centres to be reduced. To shed light on this process, we used the computer to create and analyse an enzyme-substrate complex formed from the published structure of the two proteins. It was found that the front haem edge of ferrocytochrome c was in close proximity to Trp-104 of COX and that inclusive of Trp-104, only nine amino acid residues from COX lie along a broad channel stretching from Trp-104 to the enzyme's Cu(A) centre. Six of the nine residues, Trp-104, Tyr-105, His-102 Trp 106, Asp-158 and Glu-198, had the ideal chemical properties and were properly aligned to facilitate electron transfer. Here we propose that the reduction of Trp-104 and the subsequent reduction of Cu(A) occur by a hydride/hydrogen ion relay system similar to that seen at the active site of chymotrypsin. PMID- 20583675 TI - Assessment of limited joint mobility of the hand in Black Africans with diabetes mellitus and in non-diabetics. AB - OBJECTIVE: This study is designed to further characterize Limited Joint Mobility (LJM) of the hand using quantitative goniometric measurements among Black Africans with Type 2 diabetes mellitus and non-diabetes. METHODS: Seventy-six patients with Type 2 diabetes and 63 normal controls matched for age and gender were purposively selected. Visual clinical examination and quantitative goniometric assessment of patients with DM and non-DM controls were done. The LJM was graded using the criteria of Silverstein et al. Glycaemic control and proteinuria were also assessed. RESULTS: Prevalence of LJM among Type 2 DM patients was 26.3% compared with 4.8% in normal controls. Subjects with LJM within the control group were significantly older than those with LJM within the DM group (p < 0.05). Prayer sign was 11.8% in DM patients compared with 4.8% of control. The flattening sign demonstrated by the inability to flatten their hands on a flat surface was more in patients with DM (10.5%) compared with 4.8% in the control group. Stage II LJM with 18.4% prevalence was the commonest followed by Stage III (7.9%) among patients with DM. Poor glycaemic control was found in 85%, using fasting plasma glucose and 70%, using 2-hour postprandial blood glucose (2 hpp). CONCLUSION: We conclude that Black Africans with Type 2 DM only have moderately severe cases of LJM. PMID- 20583676 TI - Haematological, biochemical and bone density parameters in vegetarians and non vegetarians. AB - OBJECTIVE: The objective is to determine any possible differences between haematological, biochemical and bone mineral density in vegetarians (vegans and lacto-ovovegetarians) and non-vegeterians. METHODS: The examined group consisted of 100 individuals: 50 non-vegetarians and 50 vegetarians. The vegetarian group was further divided in 2 subgroups: 20 vegans and 30 lacto-ovovegetarians. In all participants, plasma levels of erythrocytes, haemoglobin, haematocrit, iron, low density lipoprotein, (LDL), high density lipoprotein (HDL) total cholesterol, triglycerides and glucose were measured. Quantitative ultrasound parameters of the right calcaneus were determined in all participants. RESULTS: The results showed that lacto-ovovegetarians had statistically significantly higher red blood cell counts and haematocrit values than non-vegetarians. Vegans also had higher haematocrit values than non-vegetarians. Statistically significant differences were found between iron plasma levels in the examined groups. Iron levels were lower in non-vegetarians than in vegans and lacto-ovovegetarians. Non-vegetarians had much higher levels of cholesterol, triglycerides and LDL than the other two groups, but there were no differences found between same values in vegans and lacto-ovovegetarians. CONCLUSION: A well planned and balanced vegetarian diet, with avoidance of risk factors, does not result in abnormalities in laboratory tests and bone status parameters. PMID- 20583677 TI - Small victories, new challenges: two decades of maternal mortality surveillance in Jamaica. AB - OBJECTIVES: The paper summarizes the changing epidemiology of maternal mortality and the new challenges as Jamaica seeks to contribute to the international goal to reduce maternal mortality by 75% worldwide between 1990 and 2015. METHODS: This is a review of Jamaica's two decades of maternal mortality surveillance experience. RESULTS: Jamaica began episodic reproductive age mortality surveys between 1981 and 1983. In order to move to continuous surveillance, maternal deaths were made a Class 1 notifiable event in 1998. Reporting has steadily improved with over 80% of deaths notified, however events in the first trimester and after the first week post-partum were less likely to be reported. While gestational hypertension remains the leading cause of death, the cause-specific mortality rate has declined in response to specific efforts to reduce its prevalence and consequences. Haemorrhage and infection also declined significantly in prevalence and rank. HIV disease moved rapidly to become the fourth-ranked cause of maternal death. Another lifestyle problem is the growing prevalence of obesity, with its contribution to deaths from heart disease, diabetes mellitus and gestational hypertension. A national maternal mortality surveillance committee has been established to monitor national trends and address policy issues. One of its first tasks will be to develop clinical guidelines to standardize management of the leading direct and indirect complications of pregnancy. CONCLUSION: Jamaica has the capacity to achieve MDG5, however local and national maternal mortality committees and health teams will have to systematically address the deficiencies identified. PMID- 20583678 TI - Jamaican youth health status 2005. AB - The purpose of this survey is to determine health-seeking behaviour, nutritional status and lifestyles of adolescents aged 10-15 years. A random sample of 3003 (1422 males and 1581 females) schoolchildren, aged 10-15 years, was studied in a cross-sectional, interviewer-administered school-based survey conducted in all school types islandwide in a nationally representative sample of Jamaican children currently attending school. Some 3003 youths, 1422 males and 1581 females were interviewed. Males and females had similar healthcare-seeking behaviour but fewer students attending schools in rural areas reported having their eyes or hearing checked, or had seen a dentist than those attending urban schools. Some twelve per cent of adolescents were overweight/obese. More females than males and more urban than rural students were overweight or obese. More boys (86.3%) were physically active in the last week than girls (75%). Physical activity peaked at age 13 years and was lowest at ages 11 and 14-15 years. Some 13% of adolescents 10-15 years old reported having had sexual intercourse, with boys being four times as likely as girls to report sexual activity (OR - 4.97; C.I. - 3.82, 6.47). The median age of sexual debut was 15.43 years for boys and over 15 years for girls. One-third of adolescents drank alcohol and 3% smoked marijuana in the past year. More boys than girls used drugs (p < 0.01). Some 14% of adolescents felt lonely, sad or wanted to cry most of the time/always. One tenth seriously considered suicide. This study concluded that most adolescents attending primary and secondary schools in Jamaica were not involved in risky behaviour. However, it reveals some critical areas of concern with regard to nutritional status and physical activity, emotional well-being, drug use and sexual activity. PMID- 20583680 TI - Acute myocardial infarction in the West Indies: early observations, current issues and future concerns. AB - In the epidemiological transition from infectious diseases in the Caribbean, chronic non-communicable diseases, including cardiovascular disease, have emerged as important public health interest. Although hypertensive heart disease predominates in Afro-Caribbean populations, ischaemic heart disease and acute myocardial infarction have also been present, but the prevalence has been somewhat under-appreciated. PMID- 20583679 TI - Health status and health maintenance practices among doctors and nurses at two hospitals in Jamaica. AB - The health of doctors and nurses is of paramount importance because they must be well to perform their jobs optimally under difficult conditions. However, the challenge of their working environment and the culture of their professions often lead to physical and mental illnesses. Despite this, there are several barriers to doctors and nurses seeking healthcare. In this study, the health status and health maintenance practices of doctors and nurses at two hospitals in Kingston, Jamaica, were assessed. This population was previously reported to have a 27% prevalence of probable mental distress based on the General Health Questionnaire 30 (GHQ30). Two hundred and twelve doctors and nurses were recruited into the study. The reported prevalence of chronic diseases was determined while mental health status was based on the GHQ30, reported signs and symptoms of stress and job satisfaction. Health maintenance practices studied included, health-seeking behaviour willingness to seek counselling, reported source of emotional support and use of alcohol and tobacco as coping strategies. Although, less than 50% of study participants reported that they were satisfied with their job, the mean number of days missed from work in the "last six months" was less than two and a half days. The mean time for "last doctor's visit" for nurses and doctors in the current study were 0.93 and 2.4 years, respectively. Females were more willing to seek medical attention than males. More than 50% reported signs and symptoms of stress and major sources of emotional support were friends (55.7%), followed by spouses (36.0%) and colleagues (12.3%). The prevalence of chronic diseases was less than 1% and alcohol and tobacco did not appear to be major coping strategies. The population appeared to be physically healthy and despite the known prevalence of probable mental distress, doctors and nurses appeared unwilling to seek healthcare. Probable barriers to seeking healthcare included confidentiality issues and the need to appear healthy to colleagues, patients and the community. PMID- 20583681 TI - C-reactive protein: adjunct to cardiovascular risk assessment. AB - OBJECTIVES: The study aimed to investigate whether elevated plasma high sensitivity C-reactive protein (hs-CRP) levels are independently associated with an increased risk of cardiovascular disease (CVD) and to then assess the effectiveness of the addition of hs-CRP testing to cardiovascular risk assessment by standard lipid screening. METHODS: A retrospective hospital-based case-control study was designed. All patients attending Cross Crossing Medical Centre (CCMC) for routine cardiovascular assessment or emergency treatment were included. Cases were defined as patients with a cardiovascular event and controls as those without an event. Data collected included blood measurements of hs-CRP and cholesterol, demographic data, drug and risk factor history. RESULTS: Odds ratio of 1.84 (95% CI 1.00, 3.38) indicated that a patient with elevated hs-CRP is 1.84 times more at risk of CVD than one with normal hs-CRP. Additionally, the association between hs-CRP and CVD was found to be independent of the other risk factors (p = 0.058). Hs-CRP ranked fourth as an indicator of risk above smoking and diabetes, and patients with both high hs-CRP and high cholesterol (OR = 9.5) were 3.5 times more at risk of CVD than someone with high cholesterol alone (OR = 6.0). CONCLUSIONS: Hs-CRP testing enhanced the clinical identification of patients at risk of cardiovascular events. It can therefore contribute to timely implementation of effective lifestyle modification and pharmaceutical intervention. PMID- 20583682 TI - Angiomyolipoma of the kidney: the experience at the University Hospital of the West Indies. AB - OBJECTIVE: Angiomyolipoma (AML) of the kidney is an uncommon tumour that, until recently, was often misdiagnosed preoperatively as renal cell carcinoma (RCC). Newer radiological techniques have allowed more accurate preoperative diagnosis which can facilitate preoperative counselling and planning for conservative therapy. This study reviews the experience with these uncommon tumours at the University Hospital of the West Indies. METHODS: All cases of AML diagnosed during the period 1980 to 2007 were retrospectively identified from the files of the Department of Pathology. From these records, selected data were retrieved and analysed. These included patient demographics, clinical history, clinical diagnosis and pathologic characteristics of the specimen submitted. The total number of primary renal tumours diagnosed in adults during the same period was also determined for comparison. RESULTS: Eleven cases of AML were identified among 149 primary renal tumours in adults. Ten of these cases occurred in women. Amongst these, a single case of tuberous sclerosis was confirmed in a patient with bilateral lesions. Excluding this patient, who was 24-years-old, ages ranged from 24 to 86 years with a mean of 44 years (median 40.5 years) and an equal number of lesions was present on each side. Abdominal or flank pain were the most common clinical symptoms, present in six cases but in three cases, the tumours were discovered incidentally. The correct clinical diagnosis was made pre operatively in a single case. By contrast, a diagnosis of RCC or other malignant tumour was proffered in eight cases. Pathologically, the maximum dimension of the seven excised tumours, in whom such information was recorded, ranged from 3.5 cm to 12 cm with a median of 7 cm. Spontaneous haemorrhage in the tumour was noted in three cases, all greater than 4.5 cm in maximum dimension. CONCLUSIONS: These data confirm that AML is uncommon at the University Hospital of the West Indies. There was an overwhelming female preponderance and patients presented, most commonly, in the 3rd to 4th decades. Tuberous sclerosis was identified in a solitary case. In this series, symptomatic lesions were > 4.5 cm in maximum dimension and haemorrhage complicated three cases. Most cases were incorrectly diagnosed preoperatively. PMID- 20583683 TI - An exploratory analysis of the epidemiology and surgical management of perforated diverticular disease over a two-year period at a referral centre in the Caribbean. AB - OBJECTIVE: We present an exploratory analysis of data collected on perforated diverticular disease (PDD) in Barbados and suggest possible areas for further study. SUBJECTS AND METHODS: All cases of perforated diverticular disease treated at the Queen Elizabeth Hospital (QEH) Barbados, between January 1, 2005 and December 31, 2006 were reviewed. The patient's age, gender location of disease, Hinchey stage, operative procedure, rate of colostomy reversal, length of hospitalization, incidence of peri-operative morbidity and postoperative mortality were analysed using principal components analysis (PCA). RESULTS: Fourteen cases of PDD were treated at the QEH during this period. Six (43%) of the patients had perforated right-sided diverticulitis (PRSD). In the PCA, Dimensions 1 and 2 were the two dimensions examined, as they both had Eigenvalues over 1. Dimension 1 can be taken as an indicator of the intensity of the disease. On dimension 2, length of hospitalization had the highest component loading (0.875). The mean hospital stay was 10.6 days in PRSD, 9.5 in left-sided perforations with primary anastomosis, and 16.2 days for those with a Hartmann's procedure. The overall peri-operative morbidity was 28% and there was no mortality in the series. CONCLUSION: This preliminary study seems to show a relatively high incidence of PRSD in a predominantly Afro-Caribbean population. More research is needed to determine the exact aetiology of this disease. In our experience, primary anastomosis in carefully selected patients with either PRSD or perforated left-sided diverticulitis (PLSD) may result in shorter hospitalization. PMID- 20583684 TI - Utility of colour Doppler sonography in patients with Graves' disease. AB - OBJECTIVE: Assessment of thyroid blood flow gives valuable information about underlying functional status. Colour Flow Doppler Sonography (CFDS) is a powerful tool which displays tissue blood flow and vascularity. Colour Flow Doppler Sonography of the thyroid gland in different subsets of patients with Graves' disease was studied to define its role in initial diagnosis and management. METHODS: Eighty consecutive patients with Graves' disease (both treated and untreated) presented to hospital between August 2007 and February 2008. All patients were evaluated with CFDS of the thyroid for size, vascularity and peak systolic velocity (PSV) of the Inferior Thyroid Artery (ITA). Pertechnate scan and thyroidal autoantibody levels were done in selected cases. The patients were divided into Untreated Graves' disease (n = 31), Graves' disease on treatment but hyperthyroid (n = 26) and euthyroid Graves' disease on therapy (n = 23). Mann Whitney U-test was used for statistical analysis and a p-value of less than 0.05 was considered significant. RESULTS: Thyroid blood flow, as assessed by PSV of ITA, was significantly higher in untreated Graves' disease than in Graves disease on treatment but hyperthyroid and euthyroid Graves respectively (61.5 +/- 19.5 versus 42.9 +/- 24.7 versus 32.2 +/- 12.9 cm/s, p < 0.05). Parenchymal vascularity of the thyroid gland was higher in hyperthyroid patients than in euthyroid patients irrespective of therapy. In both groups on therapy, the dose of carbimazole correlated with the vascularity of the gland (r = 0.492 versus 0.564, p < 0.05). Colour Flow Doppler Sonography parameters correlated significantly with pertechnate scan results giving comparable sensitivity and specificity. CONCLUSION: Assessment of thyroid blood flow by CFDS is an effective marker in the initial diagnosis of Graves' disease. Vascularity of the gland can predict long term disease course while on medical therapy. PMID- 20583685 TI - Urinary bacterial pathogens and their antimicrobial susceptibility profile for the years 2005-2007 in St Kitts. AB - OBJECTIVE: The purpose of this study is to review bacterial isolates from cases of urinary tract infection (UTI) and their antimicrobial susceptibility pattern for the years 2005-2007 in St Kitts. It is hoped that the study will be of use in the treatment of cases of UTI in St Kitts. METHODS: The laboratory records at St Francis Hospital, Basseterre, St Kitts, for bacterial isolates from cases of urinary tract infection and their susceptibility profiles for three years, 2005 2007, were retrospectively reviewed and compared. RESULTS: A total of 595 isolates of 13 species of pathogenic bacteria were recovered from cases of UTI. Escherichia coli was the predominant species recovered each year. Among the other species frequently recovered were Citrobacter spp, Enterobacter spp, Klebsiella pneumoniae and Pseudomonas aeruginosa. CONCLUSION: This study, the first of its kind from St Kitts serves to emphasize that treatment of UTI should be instituted generally on the basis of antimicrobial susceptibility tests. PMID- 20583686 TI - Are women ready to do HIV test? AB - OBJECTIVE: To identify the factors that influence the stage of change with regards to HIV testing in women (16- 45-years-old) in Westmoreland using the trans-theoretical model (TTM) of behaviour change. DESIGN AND METHODS: A structured interview-assisted questionnaire was administered to 372 pregnant and non-pregnant respondents in urban and rural areas of Westmoreland after random selection of four public health facilities. The trans-theoretical model which suggests that behaviour change process moves through five stages from pre contemplation to maintenance was used to evaluate readiness for HIV testing. RESULTS: Most pregnant women who tested previously were at the preparation stage (78.5%) while non-pregnant women who tested previously were at contemplation (68.5%). The significant predictors of being in the action or maintenance stage among pregnant women was being 20- 24-years-old, experiencing a first pregnancy and being exposed to counselling. For women who had never tested, preparation was significantly associated with being in an unstable union (non-pregnant). No significant association was found for non-pregnant, previously tested females or for pregnant women who had never tested. CONCLUSION: The majority of women lacked self-efficacy as they were unable to maintain the behaviour and did not recognize its importance in the absence of pregnancy. Interventions are needed to target non-pregnant women, especially teenagers, women over 25-years old and women in unions. Integration of testing services into all aspects of primary healthcare, established testing protocols and simultaneous marketing to selected at-risk groups will increase the uptake of HIV testing opportunities and contribute to the control of this epidemic. PMID- 20583687 TI - The epidemiology of fungaemia at the University Hospital of the West Indies, Kingston, Jamaica. AB - OBJECTIVES: To determine the epidemiology of fungaemia at the University Hospital of the West Indies (UHWI) as well as the incidence of fungaemia at the UHWI over a four-year period. METHODS: A cross-sectional survey was conducted over a one year period (2002). The RapID Yeast Plus Panel Identification kit was used to identify the yeasts found in blood while morphology and dimorphism were used to identify the single mold isolated, Histoplasma capsulatum. In addition, a retrospective review of the number of cases of fungaemia at the UHWI over a four year period from 1998 was done using the laboratory and clinical records in order to determine the incidence over this period. RESULTS: The study showed that Yeast not C albicans (YNCA) accounted for 47% of the isolates while Candida albicans accounted for 29%. Of the YNCA species, Candida tropicalis was the most common (75%), followed by C pseudotropicalis (12.5%) and C glabrata (12.5%). Cryptococcus sp accounted for 18% of all fungal isolates and there was one isolate (6%) of Histoplasma capsulatum. The medical wards had the most isolates (47%), followed by surgery (29%) and the Intensive Care Unit (ICU) [24%]. While the rate at which fungi were isolated from the blood remained constant over 1998, 1999 and 2001, this doubled in 2002 from 0.26% to 0.5%. CONCLUSION: Although the incidence of fungaemia at the UHWI has remained relatively low, there was a marked increase in the last year of the study (2002) with a doubling of the number of positive fungal cultures. Candida species account for most cases of fungaemia at the UHWI. However non-albicans Candida spp were more commonly isolated than C albicans, a trend that needs to be monitored because of its implications for therapy. PMID- 20583688 TI - Pneumococcal meningitis in Jamaican children. AB - OBJECTIVE: To describe the clinical features and outcome of pneumococcal meningitis in Jamaican children. METHODS: All patients admitted to the Bustamante Hospital for Children, during the period 1995-1999, who had pneumococcus isolated from cerebrospinal fluid (CSF) or pleocytosis in association with a blood culture isolate of pneumococcus were selected. Demographic, clinical and laboratory data were collected. RESULTS: Twenty-five (23%) of 111 patients with pneumococcal infections satisfied criteria for meningitis. The median age was 8 months (range 0.5-60 months). There were 4 (16%) cases of sickle cell disease, 2 (50%) of whom were first diagnosed during the current illness. This represents a 53-fold increased risk of pneumoccocal meningitis in patients with Sickle-cell disease based on population prevalence rates. Oxacillin resistance occurred in 3 (12%) patients, one of whom died. Mortality rate was 12% (3) with all deaths occurring in infants < 1 year. Poor outcome occurred in 36% (9) of the patients. Of the (35%) 8 survivors who had follow-up evaluation, (38%) 3 had documented hearing loss. CONCLUSIONS: Meningitis is a common clinical syndrome of invasive pneumococcal disease, occurring in 23% of cases resulting in mortality and high morbidity among Jamaican children. Local seroepidemiological studies are urgently needed to inform national vaccine decisions. As an interim plan, policymakers should consider a risk-based strategy to vaccine prophylaxis that will ensure that high risk groups such as children with sickle cell disease are offered currently available conjugate pneumococcal vaccines. PMID- 20583689 TI - Profile of tuberculous meningitis with or without HIV infection and the predicators of adverse outcome. AB - OBJECTIVES: To compare the clinical, radiological and cerebrospinal fluid (CSF) findings, at hospital admission, among adult patients with tuberculous meningitis (TBM) with or without HIV infection and to identify the factors that predict adverse outcome at six months. METHODS: A total of 82 adult patients with TBM were included (40 HIV-positive and 42 HIV-negative). Several clinical (duration of illness, Glasgow Coma Scale score, presence of high temperature, headache, cranial nerve or sphincter abnormality, seizures and endocrine dysfunction), radiological (presence of hydrocephalus, cerebral infarction and oedema, meningeal enhancement, granuloma) and cerebrospinal fluid parameters (glucose, protein, lactate, lymphocytes, neutrophils and adenosine deaminase values) were recorded along with CD4 count in the peripheral blood. Statistical analysis was performed using the chi-square test. Individual variables were evaluated as prognostic factors for adverse outcome in both groups by calculating the relative risk of association for each. RESULTS: Temperature more than 38.33 degrees C was more common in the HIV-negative group while seizures, hydrocephalus, cerebral infarction and low CD4 count occurred significantly more commonly in the HIV positive group. Hydrocephalus had strong association with severe neurological deficit and seizure with death in both the groups. CONCLUSION: Several clinical and laboratory features of TBM in patients who are HIV-positive are distinctly different from those without HIV infection; some of these have an association with the probability of adverse outcome. PMID- 20583690 TI - In-vitro fertilization: donor egg sharing for premature ovarian failure. AB - Premature ovarian failure may be a consequence of gonadotoxic cytotoxic chemotherapy or radiation therapy for malignant or systemic disease often resulting in major quality of life concerns. This is the first reported case in the English-speaking Caribbean using in-vitro fertilization (IVF) donor egg sharing in a patient who experienced premature ovarian failure following chemotherapy and radiation for Hodgkin's disease. The donor's indication was tubal factor infertility. Both patients delivered healthy infants. PMID- 20583691 TI - Chronic renal failure from the English-speaking Caribbean: 2007 data. AB - AIM: Development of the renal registry to include patients at different stages of chronic kidney disease (CKD). BACKGROUND: The 2007 renal registry include cases at different stages of CKD based on the current guidelines according to the National Kidney Foundation (NKF) Kidney Disease Outcome Initiative (K/DOQI) staging. There was an increase in the number of participating countries, with the addition of Antigua and Barbuda, St Lucia and Turks and Caicos. METHODS: Data were collected using a questionnaire form. Data were stored and analysed in Words Excel for Windows or SPSS 12.0. RESULTS: Data were available for Antigua and Barbuda (n = 43), British Virgin Islands (n = 69), Cayman Islands (n = 45), Trinidad and Tobago (n = 564), Jamaica (n = 920), Turks and Caicos (n = 64), St Lucia (n = 51) and Bahamas (n = 121). The registry identified hypertension, diabetes mellitus and Chronic Glomerulonephritis (CGN) as the commonest causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in these countries. The leading cause of death reported was listed as ischaemic heart disease/heart failure, sepsis and cerebrovascular accident. CONCLUSIONS: The majority of patients with CKD and ESRD had hypertension, diabetes mellitus and CGN as the major causes. Collection of data for patients with CKD at different stages was met with some challenges, and resulted in underestimation of the true number of persons with CKD across these Caribbean countries. More emphasis will continue to be placed on improving data collection so the true incidence, prevalence and healthcare burden of CKD is known in the Caribbean. A web based programme is being developed to improve data collection. PMID- 20583692 TI - Echocardiographic findings in an Afro-Caribbean population referred for evaluation of incidental bundle branch block on electrocardiogram. PMID- 20583693 TI - Traumatic neuroma of the lower lip. AB - Traumatic neuroma is a rare disorder that represents a reactive proliferation of neural tissue following damage to an adjacent nerve. Clinically, oral lesions usually appear as a nodule of normal or grayish white smooth surface colouration, and patients may complain of pain as a frequent symptom. We report a case of a painless lower lip traumatic neuroma, clinically misdiagnosed as lipoma, in a 24 year-old Caucasian woman. On intraoral examination, a yellowish and smooth sessile, well-delimited, painless, nodular lesion measuring 10 mm x 7 mm x 4 mm in size was observed on the mucosal lower lip. An excisional biopsy was performed and the final diagnosis was traumatic neuroma. After 18 months of follow-up, the patient is asymptomatic and there are no signs of recurrence. PMID- 20583694 TI - Rhabdomyomatous mesenchymal hamartoma: clinical overview and report of a case with spontaneous regression. AB - A case of cutaneous rhabdomyomatous mesenchymal hamartoma in a 6-year-old Afro Caribbean girl is reported with review of the literature. The lesions were fine, located on the central face and became inapparent after six months. Spontaneous regression of these lesions has not been previously reported. Although rare, continued reporting will facilitate the elucidation of the clinical features and natural history of these lesions and the relationship to disordered embryogenesis. PMID- 20583695 TI - Medical abortion in primary care: pitfalls and benefits. AB - We describe five pitfalls of medical abortion: ectopic pregnancy not terminated after misoprostol, but without negative side-effects; long-term vaginal blood loss with suspicious retained products which disappeared spontaneously; a patient with uterus myomatatosus with severe pain and retained products in the uterus; repetition of misoprostol because of retained products in the uterus after two weeks and an allergic reaction to methotrexate. Despite these pitfalls, there are enough benefits to consider medical abortion with methotrexate and misoprostol as a safe method with a high success rate of more than 91% and a good alternative for surgical abortion. An invasive procedure is not necessary, there are no long term complications and it can be performed at an earlier stage, which makes it more acceptable in society. In Curacao, where abortion is legally restricted, medical abortion is performed with methotrexate and misoprostol. In countries where abortion is legal, mifepristone and misoprostol are the first choice. PMID- 20583696 TI - Cutaneous myiasis caused by Dermatobia hominis acquired in Jamaica. AB - The authors describe a case of cutaneous myiasis caused by Dermatobia hominis in a 23-year-old Italian woman who contracted the infestation during a tour in Jamaica. The infestation was located on the back and was characterized clinically by a single inflammatory nodule. To our knowledge, this is the first case of cutaneous myiasis due to Dermatobia hominis acquired in Jamaica. PMID- 20583697 TI - Community genetic interactions mediate indirect ecological effects between a parasitoid wasp and rhizobacteria. AB - Indirect ecological effects (IEEs) clearly influence species dynamics and abundance, yet relatively little is known about how they influence the evolution of species involved. While genetic variation in the species causing and responding to the IEE has obvious effects, the influence of genetic variation in intermediate species remains unexamined. Given the often counterintuitive responses of populations to IEEs this seems a significant omission. Following a community genetics approach, we used a model tetra-trophic system (parasitoid wasp, aphid, barley, and rhizobacteria) to investigate the effect of genetic interactions within the two linking species (aphids and barley) on the IEE of rhizobacteria on wasps. We show that 12.4% of the variation in wasp size, a proxy for fitness, is explained by higher-order interactions between aphid genotype (A), barley genotype (B), and presence or absence of rhizobacteria (R) (Genotype[B] x Genotype[A] x Environment[R]). Thus, the IEE of rhizobacteria on the parasitoid wasp is influenced by the specific combination of aphid and barley genotypes that mediate the interactions. In some cases changes in the genotypes of the intermediate species completely reverse the effect of rhizobacteria on wasp size. Our work demonstrates that within-species genetic variation is important in shaping IEEs in communities, an essential component of community evolutionary processes. PMID- 20583698 TI - Lidar remote sensing variables predict breeding habitat of a Neotropical migrant bird. AB - A topic of recurring interest in ecological research is the degree to which vegetation structure influences the distribution and abundance of species. Here we test the applicability of remote sensing, particularly novel use of waveform lidar measurements, for quantifying the habitat heterogeneity of a contiguous northern hardwoods forest in the northeastern United States. We apply these results to predict the breeding habitat quality, an indicator of reproductive output of a well-studied Neotropical migrant songbird, the Black-throated Blue Warbler (Dendroica caerulescens). We found that using canopy vertical structure metrics provided unique information for models of habitat quality and spatial patterns of prevalence. An ensemble decision tree modeling approach (random forests) consistently identified lidar metrics describing the vertical distribution and complexity of canopy elements as important predictors of habitat use over multiple years. Although other aspects of habitat were important, including the seasonality of vegetation cover, the canopy structure variables provided unique and complementary information that systematically improved model predictions. We conclude that canopy structure metrics derived from waveform lidar, which will be available on future satellite missions, can advance multiple aspects of biodiversity research, and additional studies should be extended to other organisms and regions. PMID- 20583699 TI - Morphological response of songbirds to 100 years of landscape change in North America. AB - Major landscape changes caused by humans may create strong selection pressures and induce rapid evolution in natural populations. In the last 100 years, eastern North America has experienced extensive clear-cutting in boreal areas, while afforestation has occurred in most temperate areas. Based on museum specimens, I show that wings of several boreal forest songbirds and temperate songbirds of non forest habitats have become more pointed over the last 100 years. In contrast, wings of most temperate forest and early-successional boreal forests species have become less pointed over the same period. In contrast to wing shape, the bill length of most species did not change significantly through time. These results are consistent with the "habitat isolation hypothesis", i.e., songbirds evolved in response to recent changes in the amount of available habitat and associated implications for mobility. Rapid morphological evolution may mitigate, without necessarily preventing, negative consequences of habitat loss caused by humans through direct exploitation or climate change. PMID- 20583700 TI - The role of environmental variables in structuring landscape-scale species distributions in seafloor habitats. AB - Ongoing statistical sophistication allows a shift from describing species' spatial distributions toward statistically disentangling the possible roles of environmental variables in shaping species distributions. Based on a landscape scale benthic survey in the Dutch Wadden Sea, we show the merits of spatially explicit generalized estimating equations (GEE). The intertidal macrozoobenthic species, Macoma balthica, Cerastoderma edule, Marenzelleria viridis, Scoloplos armiger, Corophium volutator, and Urothoe poseidonis served as test cases, with median grain-size and inundation time as typical environmental explanatory variables. GEEs outperformed spatially naive generalized linear models (GLMs), and removed much residual spatial structure, indicating the importance of median grain-size and inundation time in shaping landscape-scale species distributions in the intertidal. GEE regression coefficients were smaller than those attained with GLM, and GEE standard errors were larger. The best fitting GEE for each species was used to predict species' density in relation to median grain-size and inundation time. Although no drastic changes were noted compared to previous work that described habitat suitability for benthic fauna in the Wadden Sea, our predictions provided more detailed and unbiased estimates of the determinants of species-environment relationships. We conclude that spatial GEEs offer the necessary methodological advances to further steps toward linking pattern to process. PMID- 20583701 TI - Deciphering the relative contributions of multiple functions within plant-microbe symbioses. AB - For microbial symbioses with plants, such as mycorrhizas, we typically quantify either the net effects of one partner on another or a single function a symbiont provides. However, many microbial symbioses provide multiple functions to plants that vary based on the microbial species or functional group, plant species, and environment. Here we quantified the relative contributions of multiple functions provided by arbuscular mycorrhizal (AM) fungi to symbiont-mediated changes in plant biomass. We used two published data sets, one that measured multiple functions (pathogen protection and nutrient uptake) on a single plant and one that measured a single function (pathogen protection) on multiple plants. Using structural equation modeling, we observed strong variation in the functional pathways by which AM fungi altered plant growth; changes in plant biomass were associated with different functions (and different AM fungal functional groups) for the different plant species. Utilizing this methodology across multiple partners and environments will allow researchers to gauge the relative importance of functions they isolate and, perhaps more importantly, those they did not consider. This baseline information is essential for establishing the specific mechanisms by which microbial symbioses influence plant diversity and to more effectively utilize these organisms in agriculture, restoration and conservation. PMID- 20583702 TI - Bias, precision, and parameter redundancy in complex multistate models with unobservable states. AB - Multistate mark-recapture models with unobservable states can yield unbiased estimators of survival probabilities in the presence of temporary emigration (i.e., in cases where some individuals are temporarily unavailable for capture). In addition, these models permit the estimation of transition probabilities between states, which may themselves be of interest; for example, when only breeding animals are available for capture. However, parameter redundancy is frequently a problem in these models, yielding biased parameter estimates and influencing model selection. Using numerical methods, we examine complex multistate mark-recapture models involving two observable and two unobservable states. This model structure was motivated by two different biological systems: one involving island-nesting albatross, and another involving pond-breeding amphibians. We found that, while many models are theoretically identifiable given appropriate constraints, obtaining accurate and precise parameter estimates in practice can be difficult. Practitioners should consider ways to increase detection probabilities or adopt robust design sampling in order to improve the properties of estimates obtained from these models. We suggest that investigators interested in using these models explore both theoretical identifiability and possible near-singularity for likely parameter values using a combination of available methods. PMID- 20583703 TI - When does local spatial structure hinder competitive coexistence and reverse competitive hierarchies? AB - Classical theory states that if conspecifics have a greater competitive effect on individuals than heterospecifics then coexistence should occur, and ecologists have spent much effort exploring ways to generate coexistence when this condition is not met. One process that has received particular attention in the last two decades is the effect of within-species aggregation and between-species segregation caused by limited dispersal. A number of theories have emerged as to how this common spatial pattern may help maintain biodiversity, and the general conclusion that has emerged is that spatial structure should almost always help competitors to coexist. But does spatial structure really always aid biodiversity? An individual-based model based on a spatial extension to the Lotka Volterra competition equations and its mathematical approximation are presented to determine how local spatial structure may affect communities in which there is strong niche differentiation. Two main results emerge from analyses of the models. First, intraspecific competition being greater than interspecific competition coexistence may no longer be sufficient to generate coexistence when spatial structure is strong; and the species with the highest intraspecific competition coefficient is likely to be excluded. Second, dominance hierarchies may be reversed so that a competitor may become the subordinate species when dispersal and competitive interactions occur over short spatial scales. Both results emerge because, even though a species may be globally rare, intense clumping means most interactions occur between conspecifics, and if this is very intense it may be sufficient to stop a species from invading. However, long-range dispersal may ameliorate these effects by reducing the frequency of conspecific interactions, and this is especially important when a species is rare since it is very likely to land in an area dominated by heterospecifics. These results are most relevant to sessile organisms that produce relatively few viable offspring that survive to adulthood and that have relatively weak dispersal. The conclusion is that within-species aggregation may hinder coexistence when the toughest competitor an individual is likely to face is a member of its own species. PMID- 20583704 TI - Life-history evolution in range-shifting populations. AB - Most evolutionary theory does not deal with populations expanding or contracting in space. Invasive species, climate change, epidemics, and the breakdown of dispersal barriers, however, all create populations in this kind of spatial disequilibrium. Importantly, spatial disequilibrium can have important ecological and evolutionary outcomes. During continuous range expansion, for example, populations on the expanding front experience novel evolutionary pressures because frontal populations are assorted by dispersal ability and have a lower density of conspecifics than do core populations. These conditions favor the evolution of traits that increase rates of dispersal and reproduction. Additionally, lowered density on the expanding front eventually frees populations on the expanding edge from specialist, coevolved enemies, permitting higher investment into traits associated with dispersal and reproduction rather than defense against pathogens. As a result, the process of range expansion drives rapid life-history evolution, and this seems to occur despite ongoing serial founder events that have complex effects on genetic diversity at the expanding front. Traits evolving on the expanding edge are smeared across the landscape as the front moves through, leaving an ephemeral signature of range expansion in the life-history traits of a species across its newly colonized range. Recent studies suggest that such nonequilibrium processes during recent population history may have contributed to many patterns usually ascribed to evolutionary forces acting in populations at spatial equilibrium. PMID- 20583705 TI - Linking precipitation and C3-C4 plant production to resource dynamics in higher trophic-level consumers. AB - In many ecosystems, seasonal shifts in temperature and precipitation induce pulses of primary productivity that vary in phenology, abundance, and nutritional quality. Variation in these resource pulses could strongly influence community composition and ecosystem function, because these pervasive bottom-up forces play a primary role in determining the biomass, life cycles, and interactions of organisms across trophic levels. The focus of this research is to understand how consumers across trophic levels alter resource use and assimilation over seasonal and interannual timescales in response to climatically driven changes in pulses of primary productivity. We measured the carbon isotope ratios (delta(13)C) of plant, arthropod, and lizard tissues in the northern Chihuahuan Desert to quantify the relative importance of primary production from plants using C3 and C4 photosynthesis for consumers. Summer monsoonal rains on the Sevilleta Long Term Ecological Research (LTER) site in New Mexico support a pulse of C4 plant production that has tissue delta(13)C values distinct from C3 plants. During a year when precipitation patterns were relatively normal, delta(13)C measurements showed that consumers used and assimilated significantly more C4-derived carbon over the course of a summer, tracking the seasonal increase in abundance of C4 plants. In the following spring, after a failure in winter precipitation and the associated failure of spring C3 plant growth, consumers showed elevated assimilation of C4-derived carbon relative to a normal rainfall regime. These findings provide insight into how climate, pulsed resources, and temporal trophic dynamics may interact to shape semiarid grasslands such as the Chihuahuan Desert in the present and future. PMID- 20583706 TI - Impact of invertebrate herbivory in grasslands depends on plant species diversity. AB - Invertebrate herbivores are ubiquitous in most terrestrial ecosystems, and theory predicts that their impact on plant community biomass should depend on diversity and productivity of the associated plant communities. To elucidate general patterns in the relationship between invertebrate herbivory, plant diversity, and productivity, we carried out a long-term herbivore exclusion experiment at multiple grassland sites in a mountainous landscape of central Germany. Over a period of five years, we used above- and belowground insecticides as well as a molluscicide to manipulate invertebrate herbivory at 14 grassland sites, covering a wide range of plant species diversity (13-38 species/m2) and aboveground plant productivity (272-1125 g x m(-2) x yr(-1)), where plant species richness and productivity of the sites were not significantly correlated. Herbivore exclusion had significant effects on the plant communities: it decreased plant species richness and evenness, and it altered plant community composition. In particular, exclusion of belowground herbivores promoted grasses at the expense of herbs. In contrast to our expectation, herbivore effects on plant community biomass were not influenced by productivity. However, effect size of invertebrate herbivores was negatively correlated with plant diversity of the grasslands: the effect of herbivory on biomass tended to be negative at sites of high diversity and positive at sites of low diversity. In general, the effects of aboveground herbivores were relatively small as compared to belowground herbivores, which were important drivers of plant community composition. Our study is the first to show that variation in the effects of invertebrate herbivory on plant communities across a landscape is significantly influenced by plant species richness. PMID- 20583707 TI - Fire and grazing in a mesic tallgrass prairie: impacts on plant species and functional traits. AB - Fire is a globally distributed disturbance that impacts terrestrial ecosystems and has been proposed to be a global "herbivore." Fire, like herbivory, is a top down driver that converts organic materials into inorganic products, alters community structure, and acts as an evolutionary agent. Though grazing and fire may have some comparable effects in grasslands, they do not have similar impacts on species composition and community structure. However, the concept of fire as a global herbivore implies that fire and herbivory may have similar effects on plant functional traits. Using 22 years of data from a mesic, native tallgrass prairie with a long evolutionary history of fire and grazing, we tested if trait composition between grazed and burned grassland communities would converge, and if the degree of convergence depended on fire frequency. Additionally, we tested if eliminating fire from frequently burned grasslands would result in a state similar to unburned grasslands, and if adding fire into a previously unburned grassland would cause composition to become more similar to that of frequently burned grasslands. We found that grazing and burning once every four years showed the most convergence in traits, suggesting that these communities operate under similar deterministic assembly rules and that fire and herbivory are similar disturbances to grasslands at the trait-group level of organization. Three years after reversal of the fire treatment we found that fire reversal had different effects depending on treatment. The formerly unburned community that was then burned annually became more similar to the annually burned community in trait composition suggesting that function may be rapidly restored if fire is reintroduced. Conversely, after fire was removed from the annually burned community trait composition developed along a unique trajectory indicating hysteresis, or a time lag for structure and function to return following a change in this disturbance regime. We conclude that functional traits and species-based metrics should be considered when determining and evaluating goals for fire management in mesic grassland ecosystems. PMID- 20583708 TI - El Nino-southern oscillation effect on a fire regime in northeastern Mexico has changed over time. AB - The El Nino Southern Oscillation (ENSO) is a climate-forcing mechanism that has been shown to affect precipitation and the occurrence of wildfires in many parts of the world. In the southern United States and northern Mexico, warm events (El Nino) are associated with moist winter conditions and fewer fires, while cool events (La Ninia) tend to favor dry winters and more fires. We tested this relationship in a region of northeastern Mexico by characterizing the historical fire regime and climatic influences: Fire regimes were reconstructed from fire scar samples collected from 100 trees in three high-elevation sites on Pena Nevada in southern Nuevo Le6n. The sites were approximately 25 ha each, and the site centers were approximately 1 km apart. The earliest recorded fire occurred in 1521 and the time period we used for analysis was 1645-1929. The sites were characterized by frequent surface fires before the 1920s. In the three sites, mean fire intervals ranged from 8.6 to 9.6 years (all fires) and 11.9 to 18.6 years (fires that scarred > or = 25% of recording trees). The per-tree mean fire return interval was 17 years, and all three sites burned in the same year seven times between 1774 and 1929. After 1929, fires were nearly eliminated in all sites, likely due to human causes. We found a temporal change in the association between ENSO events and fires; before the 1830s La Nina events were significantly associated with fire years, while after the 1830s this association was not significant. In 1998, when the most severe El Nino event of the past century occurred, the three sites experienced severe, stand-replacing fires that killed many trees that had survived multiple surface fires in the past. Prior to the 1830s, fires tended to occur during dry La Nina years, but since then both La Nina and El Nino have been associated with dry years in this region, especially during the last three decades. This result suggests that ENSO effects have changed over time in this location and that phases of ENSO are not consistent indicators of precipitation, fire occurrence, or fire behavior in this area of northeastern Mexico. PMID- 20583709 TI - Montane meadow change during drought varies with background hydrologic regime and plant functional group. AB - Climate change models for many ecosystems predict more extreme climatic events in the future, including exacerbated drought conditions. Here we assess the effects of drought by quantifying temporal variation in community composition of a complex montane meadow landscape characterized by a hydrological gradient. The meadows occur in two regions of the Greater Yellowstone Ecosystem (Gallatin and Teton) and were classified into six categories (M1-M6, designating hydric to xeric) based upon Satellite pour l'Observation de la Terre (SPOT) satellite imagery. Both regions have similar plant communities, but patch sizes of meadows are much smaller in the Gallatin region. We measured changes in the percent cover of bare ground and plants by species and functional groups during five years between 1997 and 2007. We hypothesized that drought effects would not be manifested evenly across the hydrological gradient, but rather would be observed as hotspots of change in some areas and minimally evident in others. We also expected varying responses by plant functional groups (forbs vs. woody plants). Forbs, which typically use water from relatively shallow s,oils compared to woody plants, were expected to decrease in cover in mesic meadows, but increase in hydric meadows. Woody plants, such as Artemisia, were expected to increase, especially in mesic meadows. We identified several important trends in our meadow plant communities during this period of drought: (1) bare ground increased significantly in xeric meadows of both regions (Gallatin M6 and Teton M5) and in mesic (M3) meadows of the Teton, (2) forbs decreased significantly in the mesic and xeric meadows in both regions, (3) forbs increased in hydric (M1) meadows of the Gallatin region, and (4) woody species showed increases in M2 and M5 meadows of the Teton region and in M3 meadows of the Gallatin region. The woody response was dominated by changes in Artemisia spp. and Chrysothamnus viscidiflorus. Thus, our results supported our expectations that community change was not uniform across the landscape, but instead could be predicted based upon functional group responses to the spatial and temporal patterns of water availability, which are largely a function of plant water use and the hydrological gradient. PMID- 20583710 TI - The stability of African savannas: insights from the indirect estimation of the parameters of a dynamic model. AB - Savannas are characterized by a competitive tension between grasses and trees, and theoretical models illustrate how this competitive tension is influenced by resource availability, competition for these resources, and disturbances. How this universe of theoretical possibilities translates into the real world is, however, poorly understood. In this paper we indirectly parameterize a theoretical model of savanna dynamics with the aim of gaining insights as to how the grass-tree balance changes across a broad biogeographical gradient. We use data on the abundance of trees in African savannas and Markov chain Monte Carlo methods to estimate the model parameters. The analysis shows that grasses and trees can coexist over a broad range of rainfall regimes. Further, our results indicate that savannas may be regulated by either asymptotically stable dynamics (in the absence of fire) or by stable limit cycles (in the presence of fire). Rainfall does not influence which of these two classes of dynamics occurs. We conclude that, even though fire might not be necessary for grass-tree coexistence, it nonetheless is an important modifier of grass: tree ratios. PMID- 20583711 TI - Native pollen thieves reduce the reproductive success of a hermaphroditic plant, Aloe maculata. AB - Pollen is unique among floral rewards in functioning as both a carrier of gametes and an attractant and nutritious resource for floral visitors. Animals that collect pollen without pollinating (pollen thieves) could reduce siring success of thieved plants and cause pollen limitation of seed set at the population level; however, such impacts on plant reproduction have not been demonstrated experimentally. To test these effects we added hives of native honey bees (Apis mellifera scutellata) to populations of a primarily bird-pollinated plant, Aloe maculata, in eastern South Africa. In field and aviary trials, bee addition increased pollen removal from anthers but decreased pollen deposition on stigmas, and so reduced both male and female pollination components. Further, total seed production decreased with hive addition in the aviary experiment and in three of four field populations, indicating that population-level pollen theft can also compromise reproductive success. In the field, naturally occurring allodapine bees also seemed to act as pollen thieves, outweighing the effect of honey bee hive addition at one of the four aloe populations. Our results highlight the importance of social bees as pollen thieves, even of plants that have evolved in their presence, and the role of dichogamy in promoting pollen theft. Given the commonness of both social bees and dichogamy, pollen theft is likely a much more common influence on floral ecology and evolution than suggested by the sparse literature. PMID- 20583712 TI - Vascular plant removal effects on biological N fixation vary across a boreal forest island gradient. AB - There is currently much interest in understanding how biodiversity loss affects the functioning of ecosystems, but few studies have evaluated how ecosystem processes change in response to one another following biodiversity loss. We focused on a well-described gradient of 30 forested lake islands in northern Sweden, where island size determines the occurrence of lightning-ignited wildfire, which in turn determines successional stage, plant species composition, and productivity. We investigated the effect of biodiversity loss on biological nitrogen fixation by feathermosses through an experiment consisting of factorial removals of three understory shrub species (Vaccinium myrtillis, Vaccinium vitis idaea, and Empetrum hermaphroditum) and two plant functional groups (shrubs and tree roots). We tested the hypothesis that, following vascular plant species loss, N fixation rates would be impaired by changes in pools or processes that increase extractable soil N, because changes in the supply rate of N to feathermosses should influence their demand for newly fixed N. Further, we hypothesized that the effects of removals on N fixation would depend on environmental context (i.e., island size), because it has been previously demonstrated that the effect of vascular plant species removal on N recycling pools and processes was strongest on productive islands. The data demonstrated that removal of two shrub species (V. vitis-idaea and E. hermaphroditum) negatively aflected the N fixation of Hylocomium splendens, but positively affected Pleurozium schreberi, resulting in unchanged areal N fixation rates. In the functional removal experiment, tree root removal resulted in a significant negative effect on N fixation. The effects of shrub and root removals on N fixation occurred only on small islands and thus were context dependent. This pattern did not correspond to the effect of shrub and root removal treatments on N-recycling pools or processes, which only occurred in response to specific vascular plant removals on large or medium islands. The data thus did not support our hypothesis that N fixation was directly responsive to changes in N-recycling pools or processes caused by vascular plant species removals, but instead highlighted the importance of species-specific interactions and environmental context in determining the manner in which biodiversity loss alters ecosystem processes. PMID- 20583713 TI - Impact of elevated N input on soil N cycling and losses in old-growth lowland and montane forests in Panama. AB - Nitrogen deposition is projected to increase rapidly in tropical ecosystems, but changes in soil-N-cycling processes in tropical ecosystems under elevated N input are less well understood. We used N-addition experiments to achieve N-enriched conditions in mixed-species, lowland and montane forests in Panama. Our objectives were to (1) assess changes in soil mineral N production (gross rates of N mineralization and nitrification) and retention (microbial immobilization and rapid reactions to organic N) during 1- and 9-yr N additions in the lowland forest and during 1-yr N addition in the montane forest and (2) relate these changes to N leaching and N-oxide emissions. In the old-growth lowland forest located on an Inceptisol, with high base saturation and net primary production not limited by N, there was no immediate effect of first-year N addition on gross rates of mineral-N production and N-oxide emissions. Changes in soil-N processes were only apparent in chronic (9 yr) N-addition plots: gross N mineralization and nitrification rates, NO3- leaching, and N-oxide emissions increased, while microbial biomass and NH4+ immobilization rates decreased compared to the control. Increased mineral-N production under chronic N addition was paralleled by increased substrate quality (e.g., reduced C:N ratios of litterfall), while the decrease in microbial biomass was possibly due to an increase in soil acidity. An increase in N losses was reflected in the increase in 15N signatures of litterfall under chronic N addition. In contrast, the old-growth montane forest located on an Andisol, with low base saturation and aboveground net primary production limited by N, reacted to first-year N addition with increases in gross rates of mineral-N production, microbial biomass, NO3- leaching, and N oxide emissions compared to the control. The increased N-oxide emissions were attributed to increased nitrification activity in the organic layer, and the high NO3- availability combined with the high rainfall on this sandy loam soil facilitated the instantaneous increase in NO3-leaching. These results suggest that soil type, presence of an organic layer, changes in soil-N cycling, and hydrological properties are more important indicators than vegetation as an N sink on how tropical forests respond to elevated N input. PMID- 20583714 TI - Height is more important than light in determining leaf morphology in a tropical forest. AB - Both within and between species, leaf physiological parameters are strongly related to leaf dry mass per area (LMA, g/m2), which has been found to increase from forest floor to canopy top in every forest where it has been measured. Although vertical LMA gradients in forests have historically been attributed to a direct phenotypic response to light, an increasing number of recent studies have provided evidence that water limitation in the upper canopy can constrain foliar morphological adaptations to higher light levels. We measured height, light, and LMA of all species encountered along 45 vertical canopy transects across a Costa Rican tropical rain forest. LMA was correlated with light levels in the lower canopy until approximately 18 m sample height and 22% diffuse transmittance. Height showed a remarkably linear relationship with LMA throughout the entire vertical canopy profile for all species pooled and for each functional group individually (except epiphytes), possibly through the influence of gravity on leaf water potential and turgor pressure. Models of forest function may be greatly simplified by estimating LMA-correlated leaf physiological parameters solely from foliage height profiles, which in turn can be assessed with satellite and aircraft-based remote sensing. PMID- 20583715 TI - Deforestation homogenizes tropical parasitoid-host networks. AB - Human activities drive biotic homogenization (loss of regional diversity) of many taxa. However, whether species interaction networks (e.g., food webs) can also become homogenized remains largely unexplored. Using 48 quantitative parasitoid host networks replicated through space and time across five tropical habitats, we show that deforestation greatly homogenized network structure at a regional level, such that interaction composition became more similar across rice and pasture sites compared with forested habitats. This was not simply caused by altered consumer and resource community composition, but was associated with altered consumer foraging success, such that parasitoids were more likely to locate their hosts in deforested habitats. Furthermore, deforestation indirectly homogenized networks in time through altered mean consumer and prey body size, which decreased in deforested habitats. Similar patterns were obtained with binary networks, suggesting that interaction (link) presence-absence data may be sufficient to detect network homogenization effects. Our results show that tropical agroforestry systems can support regionally diverse parasitoid-host networks, but that removal of canopy cover greatly homogenizes the structure of these networks in space, and to a lesser degree in time. Spatiotemporal homogenization of interaction networks may alter coevolutionary outcomes and reduce ecological resilience at regional scales, but may not necessarily be predictable from community changes observed within individual trophic levels. PMID- 20583716 TI - Internally driven alternation of functional traits in a multispecies predator prey system. AB - The individual functional traits of different species play a key role for ecosystem function in aquatic and terrestrial systems. We modeled a multispecies predator-prey system with functionally different predator and prey species based on observations of the community dynamics of ciliates and their algal prey in Lake Constance. The model accounted for differences in predator feeding preferences and prey susceptibility to predation, and for the respective trade offs. A low food demand of the predator was connected to a high food selectivity, and a high growth rate of the prey was connected to a high vulnerability to grazing. The data and the model did not show standard uniform predator-prey cycles, but revealed both complex dynamics and a coexistence of predator and prey at high biomass levels. These dynamics resulted from internally driven alternations in species densities and involved compensatory dynamics between functionally different species. Functional diversity allowed for ongoing adaptation of the predator and prey communities to changing environmental conditions such as food composition and grazing pressure. The trade-offs determined whether compensatory or synchronous dynamics occurred which influence the variability at the community level. Compensatory dynamics were promoted by a joint carrying capacity linking the different prey species which is particularly relevant at high prey biomasses, i.e., when grazers are less efficient. In contrast, synchronization was enhanced by the coupling of the different predator and prey species via common feeding links, e.g., by a high grazing pressure of a nonselective predator. The communities had to be functionally diverse in terms of their trade-offs and their traits to yield compensatory dynamics. Rather similar predator species tended to cycle synchronously, whereas profoundly different species did not coexist. Compensatory dynamics at the community level thus required intermediately strong tradeoffs for functional traits in both predators and their prey. PMID- 20583717 TI - Recruitment facilitation can drive alternative states on temperate reefs. AB - How the combination of positive and negative species interactions acts to drive community dynamics is a fundamental question in ecology. Here we explore one aspect of this question by expanding the theory of predator-mediated coexistence to include the potential role of facilitation between the predator and inferior competitor. To motivate and illustrate our simple model, we focus on sea-urchin algae interactions in temperate rocky reef systems and incorporate recruitment facilitation, a common characteristic of marine systems. Specifically, the model represents sea urchin grazing on macroalgae, macroalgal competition with crustose coralline algae (CCA), and facilitation of sea urchin recruitment to CCA. These interactions generate alternative stable states, one dominated by macroalgae and the other by urchins, which do not occur when recruitment facilitation of urchins to CCA is ignored. Therefore, recruitment facilitation provides a possible mechanism for alternative kelp forest and urchin barren states in temperate marine systems, where storm events or harvesting of urchins or their predators can drive switches between states that are difficult to reverse. In systems with such dynamics, spatial management such as no-take marine reserves may play a crucial role in protecting community structure by increasing the resilience to shifts between states. PMID- 20583718 TI - Coexistence mechanisms and the paradox of the plankton: quantifying selection from noisy data. AB - Many species of phytoplankton typically co-occur within a single lake, as do many zooplankton species (the "paradox of the plankton"). Long-term co-occurrence suggests stable coexistence. Coexistence requires that species be equally "fit" on average. Coexistence mechanisms can equalize species' long-term average fitnesses by reducing fitness differences to low levels at all times, and by causing species' relative fitness to fluctuate over time, thereby reducing differences in time-averaged fitness. We use recently developed time series analysis techniques drawn from population genetics to estimate the strength of net selection (time-averaged selection over a year) and fluctuating selection (an index of the variation in selection throughout the year) in natural plankton communities. Analysis of 99 annual time series of zooplankton species dynamics and 49 algal time series reveals that within-year net selection generally is statistically significant but ecologically weak. Rates of net selection are -10 times faster in laboratory competition experiments than in nature, indicating that natural coexistence mechanisms are strong. Most species experience significant fluctuating selection, indicating that fluctuation-dependent mechanisms may contribute to coexistence. Within-year net selection increases with enrichment, implying that among-year coexistence mechanisms such as trade offs between competitive ability and resting egg production are especially important at high enrichment. Fluctuating selection also increases with enrichment but is independent of the temporal variance of key abiotic factors, suggesting that fluctuating selection does not emerge solely from variation in abiotic conditions, as hypothesized by Hutchinson. Nor does fluctuating selection vary among lake-years because more variable abiotic conditions comprise stronger perturbations to which species exhibit frequency-dependent responses, since models of this mechanism fail to reproduce observed patterns of fluctuating selection. Instead, fluctuating selection may arise from internally generated fluctuations in relative fitness, as predicted by models of fluctuation-dependent coexistence mechanisms. Our results place novel constraints on hypotheses proposed to explain the paradox of the plankton. PMID- 20583719 TI - Variable direct and indirect effects of a habitat-modifying invasive species on mortality of native fauna. AB - Habitat-modifying invasive species can influence rates of predation on native prey either directly by providing protective structure or indirectly by modifying traits of prey species responding to the habitat. The alga Caulerpa taxifolia is one of the most successful invasive species of shallow-water marine systems globally, often provisioning habitat in areas previously lacking in vegetated structure. We experimentally evaluated the direct effect of Caulerpa to provide refuge for the native clam Anadara trapezia and how this balances with its influence on two trait-mediated indirect interactions that may increase Anadara's susceptibility to predators. Specifically, Caulerpa's alteration of physical and chemical properties of the surrounding water and sediment deteriorate Anadara's condition and predator resistance properties and also cause Anadara, though normally buried, to project from beneath the sediment, exposing it to predators. Our results show that Anadara are somewhat (but not consistently) protected from predators by living among Caulerpa. Shallow burial depth did not counteract this protective effect. However at times of year when predator activity diminishes and conducive environmental conditions develop, negative effects of Caulerpa habitat such as hypoxia and lowered flow may dominate. Under such situations, poor clam condition accentuates Anadara's susceptibility to mortality. Ultimately, a slight and inconsistent positive effect of Caulerpa to protect Anadara from predators is exceeded by the strong negative effect of Caulerpa on clam mortality, which is heightened by clams' weakened condition produced by chronic exposure to Caulerpa. Our results show that invasive habitat-modifying species can affect mortality of native species not simply through obvious positive direct effects of their protective structure, but indirectly through contrasting negative modification of the traits of prey species responding to the habitat. PMID- 20583720 TI - Habitat heterogeneity and activity of an omnivorous ecosystem engineer control stream community dynamics. AB - All communities vary through time. This variability originates from both intrinsic and extrinsic sources. Intrinsic sources are due to actions of organisms in a community, i.e., population dynamics and species interactions, while extrinsic variability is variability created by elements of habitat or environmental change. There is a growing appreciation that these two sources may interact, producing patterns of community variability that cannot be predicted or explained by focusing on a single source. We performed a field experiment that simultaneously manipulated trophic structure (intrinsic) and habitat heterogeneity (extrinsic) in order to examine the interaction between sources of variability in a South Carolina (USA) stream macroinvertebrate community. To manipulate trophic structure, we experimentally altered local abundances of crayfish which are keystone species and ecosystem engineers, while our manipulation of habitat was to alter stream substrate heterogeneity. We focused on two types of community variability as responses to our manipulations: aggregate variability (i.e., variability of summed species) and compositional variability (i.e., variability in relative abundances of species) by monitoring community composition through a 10-week experiment. We found that community dynamics shifted from patterns in variability indicative of synchrony (high aggregate variability + low compositional) to variability indicative of compensation (low aggregate variability + high compositional) along a gradient of increasing habitat heterogeneity. However, the shift in community dynamics only occurred when crayfish were present in the community. Supporting evidence from the experiment suggested that sediment engineering effects of crayfish acted as a community-wide perturbation in low-heterogeneity habitat creating synchronous dynamics. However, in high-heterogeneity enclosures, crayfish effects were moderated by refugia provided by a more complex substratum. The switch from synchronous to compensatory dynamics is significant since compensation stabilizes aggregate community properties and ecosystem functions while synchrony frequently exacerbates aggregate variability. Results from this experiment demonstrate that an interaction between intrinsic and extrinsic sources of variability can alter community dynamics and that such an alteration does not occur in the absence of an interaction. PMID- 20583721 TI - Colonization of the Lesser Antilles by land birds. AB - This study addresses characteristics of source and island populations of nonraptorial land birds that have colonized the Lesser Antilles to determine whether colonization by individual source populations is a continuous process or occurs in transient phases. Species were classed as non-colonists, recent colonists, old endemic residents in the Lesser Antilles, and old endemic taxa that had recently spread within the archipelago. If colonization were transient, source populations of recent colonists would be more widely distributed than source populations of older, endemic island species. I compared the ecological and geographic distributions of source populations and island populations for each of the colonization groups based on a variety of literature and field data. Ages of colonization events and spread within the islands were determined by sequence divergence in mitochondrial genes, where available; relative ages were otherwise inferred from taxonomic differentiation and gaps in island distribution. Within the Lesser Antilles, old colonists, whether endemic or recently spread, tended to inhabit forest rather than open environments. Recently spread old colonists, like young colonists, had relatively greater abundance and broader habitat distribution within islands. These patterns were paralleled in northern South American source populations, but the trends were relatively weak. The strongest pattern was the propensity for source populations of young colonists and older, re-expanded endemics to occur independently on islands off the Caribbean coast of Venezuela. In comparisons with non-colonists in Trinidad, species that have recently colonized the Lesser Antilles tended to occur in more open habitats and to be more abundant locally, as well as more widespread through continental zoogeographical zones. Nested ANOVA based on a taxonomic hierarchy demonstrated that relative abundance and ecological and geographic distributions are labile, most of the variation being among species within genera. This is consistent with the idea that periods of high population productivity leading to colonization of offshore islands are transient. The existence of such phases can be inferred from correlations, albeit weak, between the status of populations in the Lesser Antilles and the ecological and geographic distribution of their putative source populations in the mainland. PMID- 20583722 TI - Many routes lead to Rome: potential causes for the multi-route migration system of Red Knots, Calidris canutus Islandica. AB - Migrants, such as birds or representatives of other taxa, usually make use of several stopover sites to cover the distance between their site of origin and destination. Potentially, multiple routes exist, but often little is known about the causes and consequences of alternative migration routes. Apart from their geographical distribution, the suitability of potential sites might play an important role in the animals' decisions for a particular itinerary. We used an optimal-migration model to test three nonmutually exclusive hypotheses leading to variations in the spring migration routes of a subspecies of Red Knot, Calidris canutus islandica, which migrates from wintering grounds in Western Europe to breeding grounds in Greenland and the Canadian Arctic: the breeding location hypothesis, the energy budget hypothesis, and the predation risk hypothesis. Varying only breeding location, the model predicted that birds breeding in the Canadian Arctic and on West Greenland stop over on Iceland, whereas birds breeding in East and Northeast Greenland migrate via northern Norway, a prediction that is supported by empirical findings. Energy budgets on stopover sites had a strong influence on the choice of route and staging times. Varying foraging-intensity and mass-dependent predation risk prompted the birds to use less risky sites, if possible. The effect of simultaneous changes in the energy budget and predation risk strongly depended on the site where these occurred. Our findings provide potential explanations for the observations that C. canutus islandica uses a diverse array of migration routes. Scrutinizing the three alternative driving forces for the choice of migratory routes awaits further, specific data collection in rapidly developing fields of research (e.g., predation risk assessment, GPS tracking). Generally, the type of modeling presented here may not only highlight alternative explanations, but also direct follow-up empirical research. PMID- 20583723 TI - Predator proximity as a stressor in breeding flycatchers: mass loss, stress protein induction, and elevated provisioning. AB - We investigated the physiological and behavioral consequences for prey breeding at different distances from a nesting predator. In a natural setting, Pied Flycatchers (Ficedula hypoleuca) made territory location decisions relative to established Sparrowhawk (Accipiter nisus) nests. From female flycatchers attending nests at different distances from Sparrowhawk nests, we measured body mass, blood stress protein (HSP60 and HSP70), and plasma immunoglobulin levels at the beginning (initial) and end (final) of the flycatcher breeding cycle, and provisioning rates during the nestling phase. We found that individuals breeding in closer proximity to Sparrowhawk nests, under higher perceived predation risk, showed significantly lower body mass, higher stress protein and immunoglobulin levels, and higher nestling provisioning rates compared to those individuals breeding farther away. Across the range of distances investigated (30-610 m), final stress protein levels decreased linearly with distance, whereas the final measures of the other variables showed unimodal trends, increasing or decreasing until an intermediate distance (approximately 350 m) and reversing the direction of the trend. Within 300 m, however, all measures showed significant linear associations with distance from the Sparrowhawk nest. Body mass and stress protein associations with distance from Sparrowhawk nests were only present during late breeding, and not in early incubation. Spatial proximity to Sparrowhawk nests consistently explained significant variation in both physiological and behavioral measures, despite the multitude of potential sources of variation for these measures in a natural setting. This suggests that predictable spatial patterns in these measures in avian communities are determined by the sites of breeding predators. Habitat selection decisions of migrant prey that vary only slightly spatially have consequences even at the cellular level, which plausibly have impacts on individual survival. In addition, this study suggests that predation risk is an important factor affecting physiological condition of prey, including stress protein induction in terrestrial vertebrates. PMID- 20583724 TI - Foraging decisions of bison for rapid energy gains can explain the relative risk to neighboring plants in complex swards. AB - Herbivores commonly base their foraging decisions not only on the intrinsic characteristics of plants, but also on the attributes of neighboring species. Although herbivores commonly orient their food choices toward the maximization of energy intake, the impact of such choices on neighboring plants remains largely unexplored. We evaluated whether foraging decisions by herbivores aiming at a rapid intake of digestible energy could explain multiple neighboring effects in complex swards. Specifically, we assessed how spatial patterns of occurrence of Carex atherodes, a highly profitable sedge species, could control the risk of bison (Bison bison) herbivory for seven other plant species. The foraging behavior of 70 free-ranging bison was evaluated in their natural environment during summer, and then related to plant characteristics. We used this information to estimate the instantaneous intake rate of digestible energy at individual feeding stations. We found that neighbor contrast defense and associational susceptibility can both be explained by simple foraging rules of energy maximization. Energy gains were higher when C. atherodes was consumed while avoiding the species for which we detected neighbor contrast defense. The lower intake rate associated with their consumption was due to an increase in handling time caused by their small size relative to C. atherodes. Bison also had higher energy gains by consuming instead of avoiding the plant species that experienced associational susceptibility. Because most of these plants were at least as tall as C. atherodes, their presence increased the heterogeneity of the grazed stratum. Avoiding their consumption increased handling time thereby reducing the instantaneous rate of energy intake. Overall, we found that bison adjust their fine-scale foraging decisions to vertical and horizontal sward structures in a way that maximizes their energy intake rate. Energy maximization principles thus provide a valuable framework to evaluate a broad-range of neighboring effects for prey faced with generalist consumers. PMID- 20583725 TI - On goodness-of-fit measure for dendrogram-based analyses. AB - Clustering methods are widely used tools in many aspects of science, such as ecology, medicine, or even market research, that commonly deal with dendrogram based analyses. In such analyses, for a given initial dissimilarity matrix, the resulting dendrogram may strongly vary according to the selected clustering methods. However, numerous dendrogram-based analyses require adequate measurement for assessing of which of the clustering methods preserves most faithfully the initial dissimilarity matrix. While cophenetic correlation coefficient-based measures have been widely used for this purpose, we emphasize here that it is not always a suitable approach. We thus propose a measure based on a matrix norm, the 2-norm, to adequately check which of the resulting ultrametric distance matrices related to the dendrograms is the closest to the initial dissimilarity matrix. In addition, we also propose an objective way to define a benchmark value (threshold value) in order to assess whether the degree of conformity between the ultrametric distance matrix selected and the initial dissimilarity matrix is satisfactory. Our proposal may notably be incorporated within a recently proposed approach that involves the use of clustering methods in environmental science and beyond. In ecology, various functional diversity indices based on clustering species from their functional dissimilarities may benefit from this overall approach. PMID- 20583726 TI - Latitudinal variation in seasonal activity and mortality in ratsnakes (Elaphe obsoleta). AB - The ecology of ectotherms should be particularly affected by latitude because so much of their biology is temperature dependent. Current latitudinal patterns should also be informative about how ectotherms will have to modify their behavior in response to climate change. We used data from a total of 175 adult black ratsnakes (Elaphe obsoleta) radio-tracked in Ontario, Illinois, and Texas, a latitudinal distance of >1500 km, to test predictions about how seasonal patterns of activity and mortality should vary with latitude. Despite pronounced differences in temperatures among study locations, and despite ratsnakes in Texas not hibernating and switching from diurnal to nocturnal activity in the summer, seasonal patterns of snake activity were remarkably similar during the months that snakes in all populations were active. Rather than being a function of temperature, activity may be driven by the timing of reproduction, which appears similar among populations. Contrary to the prediction that mortality should be highest in the most active population, overall mortality did not follow a clinal pattern. Winter mortality did increase with latitude, however, consistent with temperature limiting the northern distribution of ratsnakes. This result was opposite that found in the only previous study of latitudinal variation in winter mortality in reptiles, which may be a consequence of whether or not the animals exhibit true hibernation. Collectively, these results suggest that, at least in the northern part of their range, ratsnakes should be able to adjust easily to, and may benefit from, a warmer climate, although climate-based changes to the snakes' prey or habitat, for example, could alter that prediction. PMID- 20583727 TI - Functional leaf traits and biodiversity effects on litter decomposition in a stream: comment. PMID- 20583728 TI - A pilot study of Hungarian discourse markers. AB - This study is the first attempt at detecting formal and positional characteristics of single-word simple discourse markers in a spontaneous speech sample of Hungarian. In the first part of the research, theoretical claims made in the relevant literature were tested. The data did not confirm or only partially confirmed the claims that Hungarian discourse markers (i) occur in turn initial position and (ii) are prosodically independent, that is, are flanked by a pause on either side. In the second part, we looked at word forms both occurring as discourse markers and having syntactic functions in order to determine the features and cues which help us during speech perception to identify and distinguish between syntactic and discourse marking functions. The points of analysis were as follows: the position of the given word form in the clause, the degree of lenition in its articulation, the duration of the word form, the modulation of fundamental frequency, and the occurrence of sentence stress, if any, on the word form at hand. The results show that one or the other, or some combination, of these various factors may play a role in the perception process in certain instances only; this suggests that other parameters, yet to be explored, are also involved in the identification of these functions. PMID- 20583729 TI - Retroflexion of voiced stops: data from Dhao, Thulung, Afar and German. AB - The present article illustrates that the specific articulatory requirements for voiced alveolar or dental stops can cause tongue tip retraction and tongue mid lowering and thus retroflexion of voiced front coronals. This retroflexion is shown to have occurred diachronically in the three typologically unrelated languages Dhao (Malayo-Polynesian), Thulung (Sino-Tibetan), and Afar (East Cushitic). In addition to the diachronic cases, we provide synchronic data for retroflexion from an articulatory study with four speakers of German, a language usually described as having alveolar stops. With these combined data we supply evidence that voiced retroflex stops (as the only retroflex segments in a language) could have emerged from dental or alveolar voiced stops because the voiced front coronal plosive /d/ is generally articulated in a way that favors retroflexion, that is, with a smaller and more retracted place of articulation and a lower tongue and jaw position than /t/. The present proposal thereby supplements the observation made by Haudricourt (1950), Greenberg (1970), Bhat (1973), and Ohala (1983) that retroflex voiced stops can emerge from voiced coronal implosives for articulatory and aerodynamic reasons. PMID- 20583730 TI - Identification of acoustically modified Mandarin tones by non-native listeners. AB - This study investigated identification of fragmented Mandarin tones by non-native listeners. Monosyllabic Mandarin words were digitally processed to generate intact, silent-center, center-only, and onset-only syllables. The syllables were recorded with two carrier phrases such that the offset of the carrier tone and the onset of the target tone were either continuous or discontinuous in fundamental frequency (F0). The syllables were presented with an original carrier phrase, excised from the carrier phrase, or excised and cross-spliced with another carrier phrase. Response accuracy and reaction time were measured, and tone confusion patterns were analyzed. Overall, tone identification varied as a function of modification and tone. Intact and center-only syllables were identified more accurately than silent-center and onset-only syllables. Tone 2 was consistently the most challenging tone to identify. Although the performance level of the third-year students approached that of native listeners reported in Lee, Tao, and Bond (2008), the non-native listeners did not show evidence of using coarticulatory information. Nonetheless, the continuity or discontinuity in F0 between the carrier and target tones did affect tone identification, suggesting the influence of context in non-native tone identification. PMID- 20583731 TI - Height differences in English dialects: consequences for processing and representation. AB - This study examines the role of abstractness during the activation of a lexical representation. Abstractness and conflict are directly modeled in our approach by invoking lexical representations in terms of contrastive phonological features. In two priming experiments with English nouns differing only in vowel height of their stem vowels (e.g.,pin vs. pan), we compare a conflict versus non-conflict situation across English dialects. Based on differences in the vowel height representation, the conflict occurs in American English, but not in New Zealand English. The results show that there is a lack of priming in the conflict, but not in the non-conflict situation. This is taken as evidence for the claim that lexical access is sensitive to conflicts and non-conflicts between acoustic phonetic and phonological information. We therefore conclude that discrete phonological features are crucial determiners for successful speech perception, which is in line with abstractionist approaches. PMID- 20583732 TI - Cross-language perception of non-native tonal contrasts: effects of native phonological and phonetic influences. AB - This study examined the perception of the four Mandarin lexical tones by Mandarin naive Hong Kong Cantonese, Japanese, and Canadian English listener groups. Their performance on an identification task, following a brief familiarization task, was analyzed in terms of tonal sensitivities (A-prime scores on correct identifications) and tonal errors (confusions). The A-prime results revealed that the English listeners' sensitivity to Tone 4 identifications specifically was significantly lower than that of the other two groups. The analysis of tonal errors revealed that all listener groups showed perceptual confusion of tone pairs with similar phonetic features (T1-T2, T1-T4 and T2-T3 pairs), but not of those with completely dissimilar features (T1-T3, T2-T4, and T3-T4). Language specific errors were also observed in their performance, which may be explained within the framework of the Perceptual Assimilation Model (PAM: Best, 1995; Best & Tyler, 2007). The findings imply that linguistic experience with native tones does not necessarily facilitate non-native tone perception. Rather, the phonemic status and the phonetic features (similarities or dissimilarities) between the tonal systems of the target language and the listeners' native languages play critical roles in the perception of non-native tones. PMID- 20583733 TI - Collagen injection for correcting vocal fold asymmetry: high-speed imaging. AB - OBJECTIVES: We hypothesized that high-speed digital imaging with videokymographic and laryngotopographic analysis would provide a quantitative method to evaluate the effect of collagen injection for the correction of asymmetric and irregular vocal fold vibration in unilateral vocal fold paralysis. METHODS: Videokymographic and laryngotopographic analysis was performed for high-speed digital recordings of vocal fold vibration for visualizing the glottal vibratory patterns, and for quantifying the frequency of vibration of each vocal fold, respectively, including comparisons between the paralyzed and normal vocal folds before and after surgery. This included prospective observations of 11 subjects with unilateral vocal fold paralysis (4 male, 7 female; mean +/- SD age, 67.1 +/- 12.0 years) using high-speed digital image analysis before and after collagen injection. RESULTS: Analysis of the laryngotopographs revealed 2 distinct frequencies of vibration for the paralyzed and contralateral vocal folds for 8 of the 11 subjects before surgery. After collagen injection, the vibration frequencies became identical, despite asymmetric vibration amplitudes. Asymmetric vibration amplitudes were also observed in the other 3 subjects before surgery, but the amplitudes became symmetric after collagen injection, despite a persistent phase shift. CONCLUSIONS: Asymmetric vibration in vocal fold paralysis was exemplified by differences in vibration frequency and amplitude between the vocal folds. The present study showed that after collagen injection, these aspects of vibratory patterns improved toward symmetry. This surgical procedure could improve the functional symmetry of the larynx for phonation. PMID- 20583734 TI - High-resolution manometry of pharyngeal swallow pressure events associated with head turn and chin tuck. AB - OBJECTIVES: We quantified the effect of swallowing maneuvers on pharyngeal pressure events using high-resolution manometry. METHODS: Seven subjects swallowed multiple 5-mL water boluses in 3 different postural conditions: neutral, head turn, and chin tuck. Pressure and timing events were recorded with a 36-sensor high-resolution manometry catheter. We analyzed the regions of the velopharynx and the base of the tongue for maximum pressure, rate of pressure increase, pressure gradient, and duration of pressure above baseline. In the region of the upper esophageal sphincter (UES), we analyzed the duration of pressure declination, minimum pressure during UES opening, and maximum pressures before and after UES opening. RESULTS: The maneuvers did not have a significant effect on maximum pressure, rate of pressure increase, or pressure gradients in the velopharyngeal or tongue base regions. The duration of pressure above baseline was significantly longer in the velopharynx for head turn. The preswallow maximum UES pressure was significantly greater for neutral swallows than for head turn, and the postswallow maximum pressure was significantly lower for chin tuck. Both maneuvers appeared to prolong UES pressure declination duration, but neither prolongation reached significance. CONCLUSIONS: High resolution manometry allows for optimal spatial and temporal resolution during recording of pressure events along the length of the pharynx, and revealed previously undetected task-dependent pressure and timing differences during chin tuck and head turn in healthy adults. These maneuvers appear to influence the UES to a greater degree than the velopharynx or the tongue base. Further studies designed to quantify the effect of other maneuvers and bolus consistencies on the generation of pharyngeal pressure events both in normal and in disordered subjects may lead to hypothesis-driven, optimal, individualized swallowing therapies. PMID- 20583735 TI - Bioactive glass S53P4 in the filling of cavities in the mastoid cell area in surgery for chronic otitis media. AB - OBJECTIVES: Chronic infection of the middle ear and cholesteatoma can be treated surgically by exenteration of the mastoid air cells behind the ear. After a procedure with the canal wall-down technique, a cavity remains that is sometimes difficult to clean, collects crust, and becomes repeatedly infected. Such problematic mastoid cavities can be eliminated by filling the created cavity surgically after thorough removal of mucous membranes and cleaning of the bone. METHODS: We treated 7 patients with cavities after canal wall-down surgery for the treatment of chronic suppurative otitis media or cholesteatoma by filling the difficult-to-clean cavity in the mastoid cell area with granules of bioactive glass (BAG) S53P4 to avoid further retraction formation. The area with BAG was carefully closed with a musculoperiosteal flap. RESULTS: After the canal wall down tympanomastoidectomy, the mastoid cavities were successfully filled in all 7 patients. No biomaterial-associated infection was seen, and no disadvantages for the patients due to the BAG were observed. The cavity in the mastoid cell area decreased in size in all patients treated. CONCLUSIONS: This BAG seems to be a promising material for filling mastoid cavities after canal wall-down tympanomastoidectomy. PMID- 20583736 TI - Characterization of supraglottic phonation in children after airway reconstruction. AB - OBJECTIVES: We examined select acoustic (signal type), aerodynamic, and perceptual measures and associated surgical data in a cohort of children who were endoscopically identified as using supraglottic phonation after undergoing airway reconstruction. METHODS: Twenty-one children (4 to 18 years of age) who were seen in the Cincinnati Children's Hospital Medical Center for Pediatric Voice Disorders and identified as using supraglottic phonation were included in this study. According to standard protocol, each of these children underwent acoustic, aerodynamic, and perceptual analyses and laryngeal imaging. Their medical records were reviewed for surgical history. RESULTS: Four primary supraglottic compression patterns and 3 distinct sound sources for voice were identified. Signal type classification revealed that 20 of 21 voice signals were either type II or type III. Signal type was moderately associated with compression pattern (p = 0.01). No statistically significant findings were found in testing the Consensus Auditory Perceptual Evaluation of Voice (CAPE-V) Overall Severity score against compression patterns and vibration source. The mean Strain scores for participants who used a combined source of vibration were significantly higher than for those who used their ventricular folds. CONCLUSIONS: The compensatory compression patterns and alternate sources of vibration used by these children resulted in moderate to severe dysphonias. How children compensate after undergoing airway reconstruction has important implications for behavioral and surgical interventions aimed at improving voice quality. Not all aspects of traditional voice evaluation are suitable for this population. PMID- 20583737 TI - Dysphagia, stricture, and pneumonia in head and neck cancer patients: does treatment modality matter? AB - OBJECTIVES: Dysphagia-related sequelae are common after head and neck cancer treatment. Our aims were 1) to document overall and site-specific dysphagia, stricture, and pneumonia rates in a Medicare population, 2) to calculate treatment-specific rates and adjusted odds of developing these complications, and 3) to track changes in rates between 1992 and 1999. METHODS: Head and neck cancer patients between 1992 and 1999 were identified in combined Surveillance Epidemiology and End Results (SEER) registry and Medicare databases. Multivariate analyses determined odds of dysphagia, stricture, and pneumonia based on modality. RESULTS: Of 8,002 patients, 40% of experienced dysphagia, 7% stricture, and 10% pneumonia within 3 years of treatment. In adjusted analyses, patients treated with chemoradiation had more than 2.5-times-greater odds of dysphagia than did those treated with surgery alone. Combined therapy was associated with increased odds of stricture (p<0.05). The odds of pneumonia were increased in patients treated with radiation with or without chemotherapy. Temporally, the dysphagia rates increased 10% during this period (p<0.05). CONCLUSIONS: Sequelae of head and neck cancer treatment are common and differ by treatment regimen. Those treated with chemoradiation had higher odds of experiencing dysphagia and pneumonia, whereas patients treated with any combined therapy more commonly experienced stricture. These sequelae represent major sources of morbidity and mortality in this population. PMID- 20583738 TI - Normal muscular activity during swallowing as measured by surface electromyography. AB - OBJECTIVES: Speech-language pathologists use surface electromyography biofeedback as a tool to facilitate swallowing treatment, particularly to improve swallowing strength and coordination. The present study sought to establish normative data of swallowing muscular activity as measured by surface electrodes in order to compare the performance of patients with dysphagia to normal swallow performance. METHODS: Thirty normal young (18 to 25 years of age) and elderly (60 or more years of age) subjects swallowed 3 bolus volumes (5, 10, and 20 mL) in 2 conditions: swallow-to-command and swallow-when-ready. Swallow muscular activity was measured in microvolts with a portable biofeedback unit. RESULTS: There were significant differences between the 2 swallowing conditions in both age groups. Neither age nor bolus volume had a significant effect on the findings. CONCLUSIONS: In using surface electromyography biofeedback as an adjunct to swallowing rehabilitation, it may be more beneficial to use swallow-to-command techniques if one is interested in measuring maximum effort, regardless of patient age or volume selected. PMID- 20583739 TI - Fatal case of tumor-associated hemorrhage in a large vestibular schwannoma. AB - Vestibular schwannomas are benign neoplasms that arise from Schwann cells of the eighth cranial nerve. Most manifest clinically with tinnitus, unilateral sensorineural hearing loss, and dysequilibrium secondary to compression of the vestibulocochlear nerve; major adverse events such as intratumoral hemorrhage causing acute neurologic deterioration are rare. We report the case of a 69-year old man with a large vestibular schwannoma who required anticoagulation for several medical comorbidities. The patient began having progressively worsening neurologic symptoms, including facial nerve paralysis and dysequilibrium, which confined him to a wheelchair. After presentation, the patient was admitted to the hospital. Several days after alteration of his anticoagulation therapy in preparation for surgery, he developed intracranial hemorrhage. Attempts were made to stabilize the patient, including posterior fossa craniectomy and evacuation of hematoma; however, the intracranial hemorrhage ultimately resulted in a fatal outcome. During this procedure, a biopsy specimen was obtained, showing benign vestibular schwannoma. The literature for intratumoral hemorrhage into vestibular schwannoma and the pathologic findings in our case are reviewed. PMID- 20583740 TI - Bacterial coinfection and antimicrobial resistance in patients with paranasal sinus fungus balls. AB - OBJECTIVES: The aim of this study was to investigate the incidence of bacterial coinfection and antimicrobial resistance in cases of fungus balls of the paranasal sinuses. METHODS: Between December 1991 and August 2008, 229 patients underwent endoscopic sinus surgery or the Caldwell-Luc procedure for paranasal sinus fungus ball treatment. From 123 of these patients, a total of 124 specimens were obtained for aerobic and anaerobic culture. Antimicrobial susceptibility tests were performed. RESULTS: Ninety-one cultures (73.4%) were positive for bacteria, and 33 showed no bacterial growth. A total of 134 bacterial organisms were isolated: 65 gram-positive, 55 gram-negative, and 14 anaerobic. The most frequently isolated organisms were coagulase-negative Staphylococcus (14.9%), Staphylococcus aureus (12.7%), Enterobacter aerogenes (12.7%), viridans-group streptococci (8.9%), and Pseudomonas aeruginosa (8.2%). Among the gram-positive cocci, 12.2% were resistant to ciprofloxacin, 27.6% to clindamycin, 30% to oxacillin, 35.8% to erythromycin, 35.9% to trimethoprim-sulfamethoxazole, 56.5% to penicillin, 56.8% to gentamicin, and 0% to teicoplanin and vancomycin. Among the gram-negative rods, fewer than 10% were resistant to imipenem, piperacillin tazobactam, amikacin, gentamicin, ceftazidime, cefepime, and tobramycin, whereas more than 80% showed resistance to ampicillin and cefazolin. When we compared the data from the periods 1991 to 2000 and 2001 to 2008, there were no significant differences in the isolation rates of particular bacterial species and no significant differences in resistance rates except for clindamycin-resistant gram positive cocci and cefazolin-resistant gram-negative rods. CONCLUSIONS: Bacterial coinfections were identified in more than two thirds of patients with fungus balls and purulent secretions. This finding suggests that bacterial infection may influence the development and persistence of clinical symptoms in a substantial portion of fungus ball cases. PMID- 20583742 TI - Effect of nitric oxide synthase inhibitor on increase in nasal mucosal blood flow induced by sensory and parasympathetic nerve stimulation in rats. AB - OBJECTIVES: Neural control of nasal blood flow (NBF) has not been systematically investigated. The aim of the present study was to evaluate the effect of electrical stimulation of both sensory and parasympathetic nerves innervating the nasal mucosal arteries on NBF in rats. METHODS: In anesthetized rats, nasociliary (sensory) nerves and postganglionic (parasympathetic) nerves derived from the right sphenopalatine ganglion were electrically stimulated. We measured NBF with a laser-Doppler flowmeter. RESULTS: The nerve stimulation increased NBF on both sides and increased the mean arterial blood pressure. The increase in NBF was larger on the ipsilateral side than on the contralateral side. Hexamethonium bromide, a ganglion blocker, abolished the stimulation-induced pressure effect and the increase in NBF on the contralateral side, but did not abolish the increase in NBF on the ipsilateral side. The remaining increase in NBF was abolished by N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor. Histochemical analysis with nicotinamide adenine dinucleotide phosphate diaphorase showed neuronal nitric oxide synthase-containing nerves that innervate nasal mucosal arteries. CONCLUSIONS: Nitric oxide released from parasympathetic nitrergic nerves may contribute to an increase in NBF in rats. The afferent impulses induced by sensory nerve stimulation may lead to an increase in mean arterial blood pressure that is partly responsible for the increase in NBF. PMID- 20583743 TI - A versatile synthesis of fumaquinone. AB - Fumaquinone, a novel prenylated naphthoquinone antibiotic, was synthetized from ethyl acetoacetate in three steps (58% overall yield). The key step of the synthesis is the construction of the naphthoquinone skeleton by a regioselective Diels-Alder reaction between a 2-alkyl 1,3-bis(trimethylsilyloxy)-1,3-diene derivative and a bromoquinone. This short and versatile approach confirms the structure of fumaquinone and allows the synthesis of derivatives at the C-6 position. PMID- 20583741 TI - Biosimulation of inflammation and healing in surgically injured vocal folds. AB - OBJECTIVES: The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx. METHODS: We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma. The ABM was calibrated with empirical data on inflammatory mediators (eg, tumor necrosis factor) and extracellular matrix components (eg, hyaluronan) from published studies on surgical vocal fold injury in the rat population. RESULTS: The simulation results reproduced and predicted trajectories seen in the empirical data from the animals. Moreover, the ABM studies suggested that hyaluronan fragments might be the clinical surrogate of tissue damage, a key variable that in these simulations both is enhanced by and further induces inflammation. CONCLUSIONS: A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies. PMID- 20583744 TI - Aza-1,2,3-triazole-3-alanine synthesis via copper-catalyzed 1,3-dipolar cycloaddition on aza-progargylglycine. AB - The parallel synthesis of seven aza-1,2,3-triazole-3-alanine azapeptides of the Growth Hormone Releasing Peptide-6 (GHRP-6) was accomplished via a Cu-catalyzed azide-alkyne [3+2] cycloaddition on an aza-propargylglycine residue anchored on Rink amide resin. Circular dichroism spectroscopy in water demonstrated that azapeptides which possess an aza-1,2,3-triazole-3-alanine residue at the Trp(4) position of the GHRP-6 sequence adopt beta-turn conformations. PMID- 20583745 TI - Synthesis of guanidines from azides: a general and straightforward methodology in carbohydrate chemistry. AB - The ability of the guanidinylating reagent N',N''-diBoc-N-triflyl-guanidine (GN Tf) to react with in situ formed free amines from azides in carbohydrate scaffolds was explored. This reaction proved to be an efficient method to prepare guanidine derivatives in a one-pot manner with good to excellent yields, either with primary or secondary azides with different substitution patterns. Labile protecting groups such as benzyl ethers are not removed under these hydrogenolytic conditions. PMID- 20583746 TI - A ruthenium-rhodamine complex as an activatable fluorescent probe. AB - We describe the synthesis and characterization of a ruthenium-bipyridyl complex bearing a rhodamine-based fluorescent ligand. The complex is weakly fluorescent due to the quenching of rhodamine. Upon irradiation of the MLCT band it releases rhodamine in a fast and clean heterolytic reaction, increasing its fluorescence nearly 6-fold and making it the first visible-light activatable fluorophore based in transition metal chemistry. These properties and its lack of toxicity make it a good candidate for its use as a biologically friendly caged fluorescent probe. The use of this probe as a neuronal marker, and as a flow profiler in a thin, planar cavity and in a model flow injection analysis (FIA) is demonstrated. PMID- 20583747 TI - Co-self-assembly of binary colloidal crystals at the air-water interface. AB - A simple, fast, and cost-effective co-self-assembly approach to fabricate large area two-dimensional (2D) binary colloidal crystals has been developed. By manipulating the size ratio and number ratio of the two monodisperse polystyrene latexes, a variety of binary colloidal crystal monolayers with different structures were successfully prepared. The co-self-assembly mechanism of the 2D binary colloidal crystals at the air-water interface was investigated. It was found that the glass slide and the ethanol involved in this work had played significant roles as buffer storage and spreading agent, respectively. PMID- 20583748 TI - Uranium(VI) tetraoxido core coordinated by bidentate nitrate. AB - The synthesis and structural characterization of the compounds K[(UO(2))(2)(UO(4))(OH)(NO(3))(2)]H(2)O (1) and Ba[(UO(2))(4)(UO(4))(2)(OH)(2)(NO(3))(4)]H(2)O (2) have revealed that each contains sheets that are based upon the beta-U(3)O(8)-type topology and that these sheets are linked through low-valence interlayer cations. Consistent with other uranium(VI) compounds that have topologically identical sheets, one of the uranium(VI) sites exhibits a highly unusual (UO(4))(2-) tetraoxido core that is further coordinated by two bidentate (NO(3))(-) groups. PMID- 20583749 TI - Intramolecular sigma-bond metathesis/protonolysis on zirconium(IV) and hafnium(IV) pyridylamido olefin polymerization catalyst precursors: exploring unexpected reactivity paths. AB - A temperature-controlled metathesis/protonolysis takes place on group 4 amidopyridinate polymerization catalyst precursors. Unraveling this unprecedented reactivity path allowed us to highlight the importance of the metal precursor choice while preparing improved catalytic structures or studying new catalytic processes. PMID- 20583750 TI - Cytotoxic flavonoids as agonists of peroxisome proliferator-activated receptor gamma on human cervical and prostate cancer cells. AB - We conducted in silico screening for human peroxisome proliferator-activated receptor gamma (hPPARgamma) by performing an automated docking study with 450 flavonoids. Among the eight flavonoids as possible agonists of hPPARgamma, only 3,6-dihydroxyflavone (4) increased the binding between PPARgamma and steroid receptor coactivator-1 (SRC-1), approximately 5-fold, and showed one order higher binding affinity for PPARgamma than a reference compound, indomethacin. The 6 hydroxy group of the A-ring of 3,6-dihydroxyflavone (4) participated in hydrogen bonding interactions with the side chain of Tyr327, His449, and Tyr473. The B ring formed a hydrophobic interaction with Leu330, Leu333, Val339, Ile341, and Met364. Therefore, 3,6-dihydroxyflavone is a potent agonist of hPPAR with cytotoxic effects on human cervical and prostate cancer cells. PMID- 20583751 TI - Performance of ultrathin silicon solar microcells with nanostructures of relief formed by soft imprint lithography for broad band absorption enhancement. AB - Recently developed classes of monocrystalline silicon solar microcells can be assembled into modules with characteristics (i.e., mechanically flexible forms, compact concentrator designs, and high-voltage outputs) that would be impossible to achieve using conventional, wafer-based approaches. This paper presents experimental and computational studies of the optics of light absorption in ultrathin microcells that include nanoscale features of relief on their surfaces, formed by soft imprint lithography. Measurements on working devices with designs optimized for broad band trapping of incident light indicate good efficiencies in energy production even at thicknesses of just a few micrometers. These outcomes are relevant not only to the microcell technology described here but also to other photovoltaic systems that benefit from thin construction and efficient materials utilization. PMID- 20583752 TI - Homo- and heptanor-sterols and tremulane sesquiterpenes from cultures of Phellinus igniarius. AB - Four steroids, a homopregnene (1) and three heptanorergosterane derivatives (2 4), nine tremulane sesquiterpenes (5-13), and 18 known compounds have been isolated from cultures of the fungus Phellinus igniarius. Their structures and absolute configurations were elucidated by spectroscopic data analysis. In preliminary in vitro assays, at 10(-5) M, compounds 8, 9, 13, and 3beta-hydroxy 11,12-O-isopropyldrimene (14) showed significant vascular-relaxing activities against phenylephrine-induced vasoconstriction with relaxing rates of 35.7%, 45.4%, 46.6%, and 32.1%, respectively, as compared with the blank control. PMID- 20583753 TI - The response of Escherichia coli NikR to nickel: a second nickel-binding site. AB - The Escherichia coli transcription factor NikR mediates two levels of regulatory control of Ni(II) uptake in response to changes in the levels of available nickel. Despite the evidence that metal binding to two distinct sites on NikR, referred to as the high- and low-affinity Ni(II) sites, is required for Ni(II) selective DNA binding by the protein, the role of the latter set of Ni(II) ions in the activation of NikR remains controversial, and the position of the putative low-affinity Ni(II)-binding site(s) on NikR has not been determined. In this study we confirm that NikR has a high-affinity Ni(II)-binding site that is maintained upon DNA binding. The ligands of the low-affinity Ni(II)-binding site were examined by using selective chemical modification and mass spectrometry performed in the presence of excess Ni(II) and DNA. We localized this Ni(II) site to a region at the interface between the metal- and DNA-binding domains and identified His48 and His110 as residues that participate in the low-affinity Ni(II)-binding response. Mutation of His48 and His110 to asparagines reduces significantly both NikR's tendency to precipitate in the presence of excess Ni(II) and the affinity of the DNA-bound complex in the presence of excess Ni(II). A complete scheme involving all of the metal-binding sites that contribute to the regulatory function of E. coli NikR in nickel homeostasis is described. PMID- 20583755 TI - Controlled assembly of hydrogenase-CdTe nanocrystal hybrids for solar hydrogen production. AB - We present a study of the self-assembly, charge-transfer kinetics, and catalytic properties of hybrid complexes of CdTe nanocrystals (nc-CdTe) and Clostridium acetobutylicum [FeFe]-hydrogenase I (H(2)ase). Molecular assembly of nc-CdTe and H(2)ase was mediated by electrostatic interactions and resulted in stable, enzymatically active complexes. The assembly kinetics was monitored by nc-CdTe photoluminescence (PL) spectroscopy and exhibited first-order Langmuir adsorption behavior. PL was also used to monitor the transfer of photogenerated electrons from nc-CdTe to H(2)ase. The extent to which the intramolecular electron transfer (ET) contributed to the relaxation of photoexcited nc-CdTe relative to the intrinsic radiative and nonradiative (heat dissipation and surface trapping) recombination pathways was shown by steady-state PL spectroscopy to be a function of the nc-CdTe/H(2)ase molar ratio. When the H(2)ase concentration was lower than the nc-CdTe concentration during assembly, the resulting contribution of ET to PL bleaching was enhanced, which resulted in maximal rates of H(2) photoproduction. Photoproduction of H(2) was also a function of the nc-CdTe PL quantum efficiency (PLQE), with higher-PLQE nanocrystals producing higher levels of H(2), suggesting that photogenerated electrons are transferred to H(2)ase directly from core nanocrystal states rather than from surface-trap states. The duration of H(2) photoproduction was limited by the stability of nc-CdTe under the reactions conditions. A first approach to optimization with ascorbic acid present as a sacrificial donor resulted in photon-to-H(2) efficiencies of 9% under monochromatic light and 1.8% under AM 1.5 white light. In summary, nc-CdTe and H(2)ase spontaneously assemble into complexes that upon illumination transfer photogenerated electrons from core nc-CdTe states to H(2)ase, with low H(2)ase coverages promoting optimal orientations for intramolecular ET and solar H(2) production. PMID- 20583754 TI - An array-based method to identify multivalent inhibitors. AB - Carbohydrate-protein interactions play a critical role in a variety of biological processes, and agonists/antagonists of these interactions are useful as biological probes and therapeutic agents. Most carbohydrate-binding proteins achieve tight binding through formation of a multivalent complex. Therefore, both ligand structure and presentation contribute to recognition. Since there are many potential combinations of structure, spacing, and orientation to consider and the optimal one cannot be predicted, high-throughput approaches for analyzing carbohydrate-protein interactions and designing inhibitors are appealing. In this report, we develop a strategy to vary neoglycoprotein density on a surface of a glycan array. This feature of presentation was combined with variations in glycan structure and glycan density to produce an array with approximately 600 combinations of glycan structure and presentation. The unique array platform allows one to distinguish between different types of multivalent complexes on the array surface. To illustrate the advantages of this format, it was used to rapidly identify multivalent probes for various lectins. The new array was first tested with several plant lectins, including concanavalin A (conA), Vicia villosa isolectin B4 (VVL-B(4)), and Ricinus communis agglutinin (RCA120). Next, it was used to rapidly identify potent multivalent inhibitors of Pseudomonas aeruginosa lectin I (PA-IL), a key protein involved in opportunistic infections of P. aeruginosa , and mouse macrophage galactose-type lectin (mMGL-2), a protein expressed on antigen presenting cells that may be useful as a vaccine targeting receptor. An advantage of the approach is that structural information about the lectin/receptor is not required to obtain a multivalent inhibitor/probe. PMID- 20583756 TI - Phosphorus-nitrogen compounds. 21. Syntheses, structural investigations, biological activities, and DNA interactions of new N/O spirocyclic phosphazene derivatives. The NMR behaviors of chiral phosphazenes with stereogenic centers upon the addition of chiral solvating agents. AB - The reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6), with N/O-donor type N-alkyl (or aryl)-o-hydroxybenzylamines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrolidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted compounds (2a-2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e-3h) and trispirophosphazenes (3i-3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-amino-1-propanoxide), respectively. Compounds 3a-3d have cis and trans geometric isomers. Only the trans isomers of these compounds are isolated. Compounds 3a-3h have two stereogenic P atoms. They are expected to be in cis (meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i 3k), there are three stereogenic P atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a-3k are confirmed by (31)P NMR spectroscopy upon the addition of the chiral solvating agent; (S)-(+)-2,2,2 trifluoro-1-(9'-anthryl)ethanol. The molecular structures of 3i-3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different from that of others. Additionally, 4a and 4b are also expected to exist as cis-trans-trans and cis-cis-cis geometric isomers, but both of them are found to be in cis-trans-trans geometries. The solid-state structures of 2a, 2e, 2f, 3e, and 3f are determined by X-ray crystallography. The compounds 2f-2i, 3e-3i, and 3k are screened for antibacterial activity against gram-positive and gram negative bacteria and for antifungal activity against yeast strains. These compounds (except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f-2i, 3e-3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied. The compounds 2f-2i, 3e-3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA. PMID- 20583757 TI - Analysis of stage-specific expression of basic proteins in Leishmania infantum. AB - Prior analyses of the proteome of the protozoan parasite Leishmania have underrepresented basic proteins. Here, we applied protein fractionation by isoelectric point (pI) using free-flow electrophoresis (FFE) to study stage specific expression of basic proteins in this pathogen. Overall, we resolved 2469 protein spots in both the flagellated promastigote and the nonmotile amastigote forms in the basic range by two-dimensional gel electrophoresis (2-DE). Highly basic proteins were enriched by FFE fractionation, allowing many to be identified and characterized for the first time by proteomics analysis. Among proteins upregulated in the promastigote stage, we found glycolytic enzymes and flagellar proteins. Proteins upregulated in the amastigote stage included enzymes involved in gluconeogenesis and fatty acid beta-oxidation. In both life stages, many proteins were found in multiple spots or as proteolytic fragments, suggesting that extensive post-translational modification and processing occur. Interestingly, evidence was obtained suggesting that some of these processes may be stage-specific. PMID- 20583758 TI - Disorder-order ferroelectric transition in the metal formate framework of [NH4][Zn(HCOO)3]. AB - A three-dimensional chiral metal formate framework compound, [NH(4)][Zn(HCOO)(3)], undergoes a paraelectric-ferroelectric phase transition at 191 K triggered by the disorder-order transition of NH(4)(+) cations within the structure. PMID- 20583759 TI - Pi-extended dipyrrins capable of highly fluorogenic complexation with metal ions. AB - The synthesis and properties of a new family of pi-extended dipyrrins capable of forming brightly fluorescent complexes with metal ions are reported. The metal complexes possess tunable spectral bands and exhibit different emission properties depending on the mode of metal coordination. PMID- 20583760 TI - Reducing the symmetry of bimetallic Au@Ag nanoparticles by exploiting eccentric polymer shells. AB - We demonstrate a facile colloidal method for synthesizing Janus nanoparticles, whose eccentric polymer shells are exploited to fabricate eccentric bimetallic cores. PMID- 20583761 TI - One concept, three implementations of 3D pharmacophore-based virtual screening: distinct coverage of chemical search space. AB - Feature-based pharmacophore modeling is a well-established concept to support early stage drug discovery, where large virtual databases are filtered for potential drug candidates. The concept is implemented in popular molecular modeling software, including Catalyst, Phase, and MOE. With these software tools we performed a comparative virtual screening campaign on HSP90 and FXIa, taken from the 'maximum unbiased validation' data set. Despite the straightforward concept that pharmacophores are based on, we observed an unexpectedly high degree of variation among the hit lists obtained. By harmonizing the pharmacophore feature definitions of the investigated approaches, the exclusion volume sphere settings, and the screening parameters, we have derived a rationale for the observed differences, providing insight on the strengths and weaknesses of these algorithms. Application of more than one of these software tools in parallel will result in a widened coverage of chemical space. This is not only rooted in the dissimilarity of feature definitions but also in different algorithmic search strategies. PMID- 20583762 TI - Carotenoids in energy transfer and quenching processes in Pcb and Pcb-PS I complexes from Prochlorothrix hollandica. AB - Chlorophyll (Chl) a/b-binding proteins from Prochlorothrix hollandica known as Pcb antennae were studied by femtosecond transient absorption technique to identify energy transfer rates and pathways in Pcb and Pcb-PS I complexes. Carotenoids transfer energy to Chl with low efficiency of approximately 25% in Pcb complexes. Interestingly, analysis of transient absorption spectra identified a pathway from the hot S(1) state of zeaxanthin and/or beta-carotene as the major energy transfer channel between carotenoids and chlorophylls in Pcb whereas the S(2) state contributes only marginally to energy transfer. Due to energetic reasons, no energy transfer is possible via the relaxed S(1) state of carotenoids. The low overall energy transfer efficiency of carotenoids recognizes chlorophylls as the main light-harvesting pigments. Besides Chl a, presence of Chl b, which transfers energy to Chl a with nearly 100% efficiency, significantly broadens the spectral range accessible for light-harvesting and improves cross section of Pcb complexes. The major role of carotenoids in Pcb is photoprotection. PMID- 20583763 TI - Origin of the different activity and selectivity toward hydrogenation of single metal Au and Pt on TiO2 and bimetallic Au-Pt/TiO2 catalysts. AB - To improve the activity of Au/TiO(2) catalysts toward hydrogenation without decreasing chemoselectivity, a number of isolated and supported Au, Pt, and Au-Pt nanoparticles have been investigated by means of density functional theory (DFT) calculations. H(2) dissociation on Pt and Au-Pt nanoparticles is considerably faster than that on Au, because H(2) adsorption on Pt atoms is dissociative and no activation barriers are involved. The high chemoselectivity of Au/TiO(2) catalysts does not exist in Pt/TiO(2) catalysts no matter how small the Pt particles are, but can be preserved in Au-Pt/TiO(2) catalysts if the Au/Pt ratio is high enough as to keep Pt atoms isolated and not at the active metal-support interface. PMID- 20583764 TI - Neutron reflectivity study of the structure of pH-responsive polymer brushes grown from a macroinitiator at the sapphire-water interface. AB - Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes have been grown by surface-initiated atom transfer radical polymerization (SI-ATRP) from a polyanionic macroinitiator adsorbed at the sapphire-water interface, and neutron reflectivity has been used to characterize the structures and pH response of the brushes. The polymer brushes are well-described by Gaussian density profiles with an additional thin, dense layer close to the solid-liquid interface for the thicker brushes at pH 7 and 9, which produces a spike in the density profile. The spike in the distribution accounts for less than 5% of the polymer and disappears as the brushes swell at pH 3. The observed swelling behavior has been used in combination with the predictions of scaling theory and previous experimental measurements to determine the grafted density of PDMAEMA chains. PMID- 20583765 TI - What fraction of DNA double-strand breaks produced by the direct effect is accounted for by radical pairs? AB - The purpose of this investigation was to determine what fraction of double strand breaks (dsb's), generated by the direct effect of ionizing radiation on DNA, can be accounted for by radical pairs. A radical pair is defined as two radicals trapped within a separation distance of <3 nm. Q-band EPR was used to measure the yield of radical pairs in calf thymus DNA films X-irradiated at 4 K. The EPR spectrum of DNA showed no evidence of radical pairs. To determine the relative sensitivity for radical pair detection via Q-band EPR, we measured the yield of radical pairs in single crystals of thymine, G(rp-Thy). Under the same conditions employed for DNA, G(rp-Thy) was approximately 8 nmol/J. The value of G(rp-Thy), in conjunction with the measured signal-to-noise, was used to calculate an upper limit for the yield of radical pairs in DNA, G(max)(rp-DNA) < 0.7-1.4 nmol/J. The upper limit, G(max)(rp-DNA), was compared with the yield of dsb's, G(total)(dsb) = 10 nmol/J, previously measured in pUC18 DNA films by Purkayastha, S.; Milligan, J. R.; Bernhard, W. A. Radiat. Res. 2007, 168, 357. We found that G(total)(dsb) > 2 x G(max)(rp-DNA), implying that a significant fraction of dsb's were not derived from a pair of trappable radicals. At least one of the two precursors needed to form a dsb was a diamagnetic (molecular) product. The hypothesis is that EPR silent lesions are formed through a molecular pathway. For example, a two-electron oxidation of deoxyribose would result in a deoxyribose carbocation intermediate that ultimately leads to a strand break. PMID- 20583766 TI - Acidification of the oxygen scavenging system in single-molecule fluorescence studies: in situ sensing with a ratiometric dual-emission probe. AB - For most of the single-molecule fluorescence studies to date, biomolecules of interest are labeled with small organic dyes which suffer from their limited photostability evidenced by blinking and photobleaching. An enzymatic oxygen scavenging system of glucose oxidase and catalase is widely used to improve the dye photostability but with the unfavorable side effect of producing gluconic acid. It is known that accumulation of this byproduct in solution can lead to considerable acidification, but the uncertainty in its severity under experimentally relevant conditions has been a long-standing area of concern due to the lack of a suitable assay. In this paper we report a fluorescence-based analytical assay for quantitatively assessing the acidification of oxygen scavenging systems in situ. By using a ratiometric, dual-emission dye, SNARF-1, we observed the presence and, for the first time, measured the severity of solution acidification due to the oxygen scavenging system for a number of conditions relevant to single-molecule studies. On the basis of the quantitative analysis of the acidification profile under these conditions, practical guidelines for optimizing the oxygen scavenging system are provided. This in situ assay should be applicable to a large variety of future single-molecule fluorescence studies. PMID- 20583767 TI - Method for detection of trace metal and metalloid contaminants in coal-generated fuel gas using gas chromatography/ion trap mass spectrometry. AB - There exists an increasing need to develop a reliable method to detect trace contaminants in fuel gas derived from coal gasification. While Hg is subject to current and future regulations, As, Se, and P emissions may eventually be regulated. Sorbents are the most promising technology for the removal of contaminants from coal-derived fuel gas, and it will be important to develop a rapid analytical detection method to ensure complete removal and determine the ideal time for sorbent replacement/regeneration in order to reduce costs. This technical note explores the use of a commercial gas chromatography/ion trap mass spectrometry system for the detection of four gaseous trace contaminants in a simulated fuel gas. Quantitative, repeatable detection with limits at ppbv to ppmv levels were obtained for arsine (AsH(3)), phosphine (PH(3)), and hydrogen selenide (H(2)Se), while qualitative detection was observed for mercury. Decreased accuracy and response caused by the primary components of fuel gas were observed. PMID- 20583768 TI - Selective synthesis of Zn(1 - x)Mn(x)Se nanobelts and nanotubes from [Zn(1 - x)Mn(x)Se](DETA)0.5 nanbelts in solution (x = 0-0.15) and their EPR and optical properties. AB - Zn(1 - x)Mn(x)Se (x = 0-0.15) nanobelts and nanotubes can be synthesized via the removal of diethylenetriamine (DETA) in 1-octadecene (ODE) and ethylene glycol (EG), respectively, using [Zn(1 - x)Mn(x)Se](DETA)(0.5) nanobelts as a template. The as-prepared ZnSe nanobelts are single-crystalline and grown along the [001] direction, and the ZnSe nanotubes consist of nanoparticles assembled along the [001] direction. In addition, Mn(2+)-doped Zn(1 - x)Mn(x)Se (x = 0.05, 0.10, 0.15) nanotubes are prepared for the first time if doped [Zn(1 - x)Mn(x)Se](DETA)(0.5) nanobelts are used as the template. The formation process of Zn(1 - x)Mn(x)Se nanobelts and nanotubes has been studied, and a plausible mechanism is proposed. Photoluminescence (PL) and electron paramagnetic resonance (EPR) spectra of Zn(1 - x)Mn(x)Se nanobelts and Zn(1 - x)Mn(x)Se nanotubes have been investigated. PMID- 20583771 TI - Rovibrational energy transfer in Ne-Li2(A1Sigmau+,v=0): Comparison of experimental data and results from classical and quantum calculations. AB - Absolute rate constants for rotational and rovibrational energy transfer in the system Ne-Li2(A1Sigmau+) were measured by a dispersed fluorescence technique following excitation of the (v = 0,j = 18) initial level of Li2(A1Sigmau+). The rate coefficients for Deltav = 0 processes decline monotonically with increasing |Deltaj|. The Deltav = 1 rate coefficients are also peaked near Deltaj = 0 but show a broad shoulder extending to approximately Deltaj = 30. Classical trajectory calculations and accurate quantum mechanical close-coupled calculations were used to compute theoretical rate constants from an ab initio potential surface. The agreement between the classical and quantum calculations is very good. The calculations slightly overestimate the measured rate constants for Deltav = 0, Deltaj or= 20, implying that the anisotropy of the ab initio surface is too small at short range and too large at long range. For Deltav = 1 collisions, the calculations agree well with experiment for Deltaj 0 collisions, disagreeing with experiment by a factor of 2 for Deltaj approximately 20 but agreeing better at higher and lower Deltaj. Analysis of classical trajectories indicates that the vibrationally inelastic collisions fall into two groups corresponding to equatorial and near end impacts; the former generally produce small Deltaj while the latter produce large Deltaj. Studies of a simple model potential show that this dual mechanism may be a general phenomenon not limited to the particular potential surface employed here. Criteria controlling the relative importance of the two vibrational excitation routes are enumerated. PMID- 20583770 TI - Molecular dynamics study of the behavior of selected nanoscale building blocks in a gel-phase lipid bilayer. AB - The cellular membrane functions as a regulating barrier between the intracellular and extracellular regions. For a molecule to reach the interior of the cell from the extracellular fluid, it must diffuse across the membrane, via either active or passive transport. The rigid structure of lipid bilayers, which are a key component of cellular membranes, prohibit simple diffusion of most particles, while vital nutrients are transported to the interior by specific mechanisms, such as ion channels and transport proteins. Although the cellular membrane provides the cell with protection against unwanted toxins that may be in the extracellular medium, some foreign particles can reach the interior of the cell, resulting in irregularities in cellular function. This behavior is particularly noted for permeants with compact molecular structure, suggesting that common nanoscale building blocks, such as fullerenes, may enter into the interior of a cell. To gauge the propensity for such particles to cross the membrane, we have computed the Gibbs free energy of transfer along the axis normal to the bilayer surface for two nanoscale building blocks, C(60) and a hydrogen-terminated polyhedral oligomeric silsequioxane (H-POSS) monomer, in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer using molecular dynamics simulations and potential of mean force calculations. The studies show that C(60) has a substantial energetic preference for the soft polymer region of the lipid bilayer system, below the water/bilayer interface, with a transition energy from bulk water of -19.8 kcal/mol. The transition of C(60) from the bulk water to the center of the bilayer, while also energetically favorable, has to overcome a +5.9 kcal/mol energetic barrier in the hydrophobic lipid tail region. The H-POSS simulations indicate an energy minimum at the water-bilayer interface, with an energy of -10.9 kcal/mol; however, a local minimum of -2.7 kcal/mol is also observed in the hydrophobic dense aliphatic region. The energy barrier seen in the hydrophobic core region of the C(60) study is likely due to the significant penalty associated with inserting the relatively large particle into such a dense region. In contrast, whereas H-POSS is found to be subject to an energetic penalty upon insertion into the bilayer, the relatively small size of the H-POSS solute renders this penalty less significant. The energy barrier seen in the soft polymer region for the H-POSS monomer is primarily attributed to the lack of favorable solute-bilayer electrostatic interactions, which are present in the interfacial region, and fewer van der Waals interactions in the soft polymer region than the dense aliphatic region. These results indicate that C(60) may partition into the organic phase of the DPPC/water system, given the favorable free energies in the soft polymer and dense aliphatic regions of the bilayer, and H-POSS is likely to partition near the water-bilayer interface, where the particle has low-energy electrostatic interactions with the polar head groups of the bilayer. PMID- 20583772 TI - Investigation of conformation-dependent properties of L-phenylalanine in neutral and radical cations by using a density functional taking into account noncovalent interactions. AB - Conformation-dependent properties of l-phenylalanine in neutral and radical cations have been studied by using density functional theory (DFT) with a new density functional M05-2X, which is applicable to molecular systems with nonconvalent interactions. Adiabatic and vertical ionization energies and charge distributions in the cationic conformers in addition to optimized geometrical structures for both the neutral and the cationic conformers were evaluated. These results were compared with DFT (B3LYP) results. The M05-2X results can explain the correspondence between the observed and predicted conformers without ambiguity. The possibility of conformerization of neutral conformers is indicated from the results of IRC (intrinsic reaction coordinate) profiles. PMID- 20583773 TI - Modulation of phase separation between spherical and rodlike molecules using geometric surfactancy. AB - A Dyad consisting of C(60) linked to a pi-conjugated oligomer by a propylene spacer was synthesized to explore its ability to modulate phase separation between OFTB and PCBM using differential scanning calorimetry, hot-stage polarizing optical microscopy, X-ray diffraction, and atomic force microscopy techniques. Upon thermal annealing at 10 degrees C above its T(g) for 12-48 h, the 1:1 blend of OFTB and PCBM resulted in a eutectic mixture. Thermal annealing of a OFTB:Dyad:PCBM film with a 9:2:9 mass ratio at 10 degrees C above its T(g) for 12 h resulted in an amorphous film. Its AFM phase image indicated phase separation into two interspersed 30 nm amorphous domains at approximately equal fractions. Geometric surfactancy is inferred from the formation of microemulsions in analogy to widely reported traditional oil-surfactant-water systems and ternary polymer blends. In contrast, thermal annealing of a 7:6:7 film under a similar condition resulted in an amorphous film with compositional uniformity. PMID- 20583775 TI - Reaction and reorganization free energies of electron-transfer reactions under restricted geometry conditions. AB - Electron-transfer reactions between iron and cobalt complexes were studied in beta-cyclodextrin (betaCD), 2-hydroxypropyl-beta-cyclodextrin (HbetaCD), and 18 crown-6 ether (18C6) solutions. The results were rationalized taking as the basis the Marcus-Hush formalism. We employed two different approaches, depending on the kind of receptor and solvent, to obtain the reorganization and reaction free energies that determine the reaction rate constant. The opposite trends in reactivity observed in betaCD and HbetaCD solutions and the behavior in solutions of 18C6 are explained. PMID- 20583774 TI - Nontemplated approach to tuning the spectral properties of cyanine-based fluorescent nanoGUMBOS. AB - Template-free controlled aggregation and spectral properties in fluorescent organic nanoparticles (FONs) is highly desirable for various applications. Herein, we report a nontemplated method for controlling the aggregation in near infrared (NIR) cyanine-based nanoparticles derived from a group of uniform materials based on organic salts (GUMBOS). Cationic heptamethine cyanine dye 1,1',3,3,3',3'-hexamethylindotricarbocyanine (HMT) was coupled with five different anions, viz., [NTf(2)(-)], [BETI(-)], [TFPB(-)], [AOT(-)], and [TFP4B( )], by an ion-exchange method to obtain the respective GUMBOS. The nanoGUMBOS obtained via a reprecipitation method were primarily amorphous and spherical (30 100 nm) as suggested by selected area electron diffraction (SAED) and transmission electron microscopy (TEM). The formation of tunable self-assemblies within the nanoGUMBOS was characterized using absorption and fluorescence spectroscopy in conjunction with molecular dynamics simulations. Counterion controlled spectral properties observed in the nanoGUMBOS were attributed to variations in J/H ratios with different anions. Association with the [AOT(-)] anion afforded predominant J aggregation enabling the highest fluorescence intensity, whereas [TFP4B(-)] disabled the fluorescence due to predominant H aggregation in the nanoparticles. Analyses of the stacking angle of the cations based on molecular dynamic simulation results in [HMT][NTf(2)], [HMT][BETI], and [HMT][AOT] dispersed in water and a visual analysis of the representative simulation snapshots also imply that the type of aggregation was controlled through the counterion associated with the dye cation. PMID- 20583776 TI - Nickel-catalyzed [2 + 2 + 2] cycloaddition of two enones and an alkyne. AB - A fully intermolecular [2 + 2 + 2] cycloaddition of two enones and an alkyne has been achieved. This reaction proceeds stereoselectively to give one diastereomer as a sole product. PMID- 20583777 TI - Syntheses of copillar[5]arenes by co-oligomerization of different monomers. AB - Three copillar[5]arenes, pillar[5]arenes containing different repeating units, were successfully prepared by co-oligomerization of different monomers. It was demonstrated that the yields of pillararenes could be improved by using hydroquinone diethers with appropriate aliphatic chain lengths. Pseudorotaxane type threaded structures were obtained in the solid state by the inclusion of an n-hexane molecule into the cavity of either a homopillar[5]arene, a pillar[5]arene containing only one repeating unit, or a copillar[5]arene. PMID- 20583778 TI - Facile benzo-ring construction via palladium-catalyzed functionalization of unactivated sp3 C-H bonds under mild reaction conditions. AB - A practical synthetic method for the annulation of benzo-rings by the intramolecular coupling of an aryl iodide and a methylene C-H bond is described. The palladium-catalyzed C-H functionalization is directed by an aminoquinoline carboxamide group, which can be easily installed and removed. High yields and broad substrate scope were achieved. An additive of ortho-phenyl benzoic acid, identified from a systematic screening, functions as a critical ligand for the catalytic process under mild condition, even at near room temperature. PMID- 20583780 TI - Printed, sub-3V digital circuits on plastic from aqueous carbon nanotube inks. AB - Printing electronic components on plastic foils with functional liquid inks is an attractive approach for achieving flexible and low-cost circuitry for applications such as bendable displays and large-area sensors. The challenges for printed electronics, however, include characteristically slow switching frequencies and associated high supply voltages, which together impede widespread application. Combining printable high-capacitance dielectrics with printable high mobility semiconductors could potentially solve these problems. Here we demonstrate fast, flexible digital circuits based on semiconducting carbon nanotube (CNT) networks and high-capacitance ion gel gate dielectrics, which were patterned by jet printing of liquid inks. Ion gel-gated CNT thin-film transistors (TFTs) with 50 microm channel lengths display ambipolar transport with electron and hole mobilities >20 cm(2)/V.s; these devices form the basis of printed inverters, NAND gates, and ring oscillators on both polyimide and SiO(2) substrates. Five-stage ring oscillators achieve frequencies >2 kHz at supply voltages of 2.5 V, corresponding to stage delay times of 50 micros. This performance represents a substantial improvement for printed circuitry fabricated from functional liquid inks. PMID- 20583779 TI - Chaperone-like N-methyl peptide inhibitors of polyglutamine aggregation. AB - Polyglutamine expansion in the exon 1 domain of huntingtin leads to aggregation into beta-sheet-rich insoluble aggregates associated with Huntington's disease. We assessed eight polyglutamine peptides with different permutations of N methylation of backbone and side chain amides as potential inhibitors of polyglutamine aggregation. Surprisingly, the most effective inhibitor, 5QMe(2) [Anth-K-Q-Q(Me(2))-Q-Q(Me(2))-Q-CONH(2), where Anth is N-methylanthranilic acid and Q(Me(2)) is side chain N-methyl Q], has only side chain methylations at alternate residues, highlighting the importance of side chain interactions in polyglutamine fibrillogenesis. Above a 1:1 stoichiometric ratio, 5QMe(2) can completely prevent fibrillation of a synthetic aggregating peptide, YAQ(12)A; it also shows significant inhibition at substoichiometric ratios. Surface plasmon resonance (SPR) measurements show a moderate K(d) with very fast k(on) and k(off) values. Sedimentation equilibrium analytical ultracentrifugation indicates that 5QMe(2) is predominantly or entirely monomeric at concentrations of CO(X(1)Sigma(+)) + H((2)S) rate constant: the role of the long-range potential. AB - Faced with the lack of experimental data on the C(3P) + OH(X2Pi) --> CO(X1Sigma+) + H(2S) reaction, we propose here to compare rate constant values and their behavior with temperature following various dynamical models and, in particular, to check the sensivity of these quantities with the long-range part of the potential energy surface. For that, we have evaluated the C + OH rate constant using the quasiclassical trajectory (QCT) method, the adiabatic capture centrifugal sudden approximation (ACCSA), and the mean potential capture theory (MPCT) based on a full ab initio potential energy surface fitted with q12,5 kernels or on a perturbative multipolar expansion (MPE) potential including the monomer spin orbit splittings (MPE-SO) or not. Despite the various approximations involved in the different methods and PESs, an excellent agreement is obtained in a subset of three models: the ACCSA method with PME-SO or ab initio PESs and the QCT method with the latter PES. This suggests that the reaction takes place once the system enters the deep valley of products. In that case, the errors due to these approximate methods and PESs are small and, consequently, the rate constants are accurately calculated. Furthermore, these findings provide evidence of preponderance of the entrance channel in the reactivity of this system. PMID- 20583798 TI - Absorption cross section of ozone isotopologues calculated with the multiconfiguration time-dependent hartree (MCTDH) method: I. The Hartley and Huggins bands. AB - The absorption cross sections of 18 isotopologues of the ozone molecule have been calculated in the range of the Hartley-Huggins bands (27000-55000 cm(-1)). All 18 possible ozone isotopologues made with (16)O, (17)O, and (18)O have been considered, with emphasis on those of geophysics interest like (16)O(3) (17)O(16)O(2), (16)O(17)O(16)O, (18)O(16)O(2), and (16)O(18)O(16)O. We have used the MCTDH algorithm to propagate wavepackets. As an initial wavepacket, we took the vibrational ground state multiplied by the transition dipole moment surface. The cross sections have been obtained from the autocorrelation function of this wavepacket. Only two potential energy surfaces (PESs) and the corresponding transition dipole moment are involved in the calculation. The dissociating R state has been omitted. The calculations have been performed only for J = 0. The comparison with the experimental absorption cross sections of (16)O(3) and (18)O(3) has been performed after an empirical smoothing which mimics the rotational envelop. The isotopologue dependence of the cross sections of 18 isotopologues can be split into two energy ranges, (a) from 27000 to 32000 cm( 1), the Huggins band, which is highly structured, and (b) from 32000 to 55000 cm( 1), the main part of the cross section which has a bell shape, the Hartley band. This bell-shaped envelop has been characterized by a new analytic model depending on only four parameters, amplitude, center, width, and asymmetry. The isotopologue dependence of these parameters reveals the tiny differences between the absorption cross sections of the various isotopologues. In contrast to the smooth shape of the Hartley band, the Huggins band exhibits pronounced vibrational structures and therefore shows large isotopologue differences which may induce a significant isotopologue dependence of the ozone photodissociation rates under actinic flux. PMID- 20583799 TI - Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. AB - Circulating tumor cells (CTCs) are tumor cells circulating in the peripheral blood of patients with metastatic cancer. Detection of CTCs has clinical significance in cancer therapy because it would enable earlier diagnosis of metastasis. In this research, a microfluidic device equipped with a size selective microcavity array for highly efficient and rapid detection of tumor cells from whole blood was developed. The microcavity array can specifically separate tumor cells from whole blood on the basis of differences in the size and deformability between tumor and hematologic cells. Furthermore, the cells recovered on the microcavity array were continuously processed for image-based immunophenotypic analysis using a fluorescence microscope. Our device successfully detected approximately 97% of lung carcinoma NCI-H358 cells in 1 mL whole blood spiked with 10-100 NCI-H358 cells. In addition, breast, gastric, and colon tumor cells lines that include EpCAM-negative tumor cells, which cannot be isolated by conventional immunomagnetic separation, were successfully recovered on the microcavity array with high efficiency (more than 80%). On an average, approximately 98% of recovered cells were viable. Our microfluidic device has high potential as a tool for the rapid detection of CTCs and can be used to study CTCs in detail. PMID- 20583800 TI - Real-time electrochemical monitoring of cellular H2O2 integrated with in situ selective cultivation of living cells based on dual functional protein microarrays at Au-TiO2 surfaces. AB - This paper demonstrates a novel strategy for site-selective cell adhesion and in situ cultivation of living cells, integrated with real-time monitoring of cellular small biomolecules based on dual functional protein microarrays. The protein microarrays have been produced on the superhydrophobic|philic Au-TiO2 micropatterns, through further modification of L-cysteine (Cys) and followed by successive immobilization of a model protein, cytochrome c (cyt c). Experimental results have revealed that the created cyt c microarrays play dual functions: one is employed as a robust substrate for site-selective cell adhesion and in situ cultivation of living cells, because the protein microarrays exhibit high selectivity and bioaffinity toward cells, as well as long biostability under cell culture condition up to 7 days. Meanwhile, the cyt c microarrays can also serve as sensing elements for hydrogen peroxide (H2O2) due to the inherent enzymatic activity of the heme center in cyt c. Direct electron transfer of cyt c has been enhanced at the Cys-modified Au-TiO2 (Au-TiO2/Cys) microarrays, and the electrochemical behavior can be tuned by varying the width and spacing of the microband arrays. Furthermore, cyt c is stably immobilized on the Au-TiO2/Cys microarrays and maintains its enzymatic activity after confined on the microarrays. Thus, the optimized cyt c microarrays show striking analytical performance for H2O2 determination, e.g., high sensitivity and selectivity, broad linear range from 10(-9) M to 10(-2) M, low detection limit down to 2 nM, and short response time within 5 s. As a result, the excellent analytical properties of the cyt c microarrays, as well as the characteristic of the protein microarrays themselves, including high selectivity, long biostability, and good bioaffinity, opens up a method for selective in situ cultivation of cells integrated with real-time detection of signaling biomolecules such as H2O2 released from living cells, which shows potential for physiological and pathological investigations. PMID- 20583801 TI - First-principles study of the electronic, optical properties and lattice dynamics of tantalum oxynitride. AB - First-principles calculations of the electronic, optical properties and lattice dynamics of tantalum oxynitride are performed with the density functional theory plane-wave pseudopotential method. The analysis of the electronic structure shows a covalent nature in Ta-N bonds and Ta-O bonds. The hybridization of anion 2p and Ta 5d states results in enhanced dispersion of the valence band, raising the top of the valence band and leading to the visible-light response in TaON. It has a high dielectric constant, and the anisotropy is displayed obviously in the lower energy region. Our calculation indicated that TaON has excellent dielectric properties along [010] direction. Various optical properties, including the reflectivity, absorption coefficient, refractive index, and the energy-loss spectrum are derived from the complex dielectric function. We also present phonon dispersion relation, zone-center optical mode frequency, density of phonon states, and some thermodynamic properties. The experimental IR modes (B(u) at 808 cm(-1) and A(u) at 863 cm(-1)) are reproduced well and assigned to a combination of stretching and bending vibrations for the Ta-N bond and Ta-O bond. The thermodynamic properties of TaON, such as heat capacity and Debye temperature, which were important parameters for the measurement of crystal physical properties, were first given for reference. Our investigations provide useful information for the potential application of this material. PMID- 20583803 TI - Structure and dynamics of multiple cationic vectors-siRNA complexation by all atomic molecular dynamics simulations. AB - Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems. PMID- 20583802 TI - Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways. AB - The catalytic mechanism of carboxypeptidase A (CPA) for the hydrolysis of ester substrates is investigated using hybrid quantum mechanical/molecular mechanical (QM/MM) methods and high-level density functional theory. The prevailing mechanism was found to utilize an active-site water molecule assisted by Glu270, and this so-called promoted-water pathway is similar to that in the CPA catalyzed proteolytic reaction (D. Xu and H. Guo, J. Am. Chem. Soc. 2009, 131, 9780). On the other hand, our simulations indicated the existence of an alternative pathway due to direct nucleophilic attack of Glu270 on the scissile carbonyl carbon. This so-called nucleophilic pathway, which is not viable in proteolytic reactions, leads to a stable acyl-enzyme complex. However, the nucleophilic pathway is nonproductive as it is blocked by a high barrier in the deacylation step. On the basis of results reported here and in our earlier publication, a unified model is proposed to account for nearly all experimental observations concerning the catalysis of CPA. PMID- 20583804 TI - Partial nitrification/denitrification can be attributed to the slow response of nitrite oxidizing bacteria to periodic anoxic disturbances. AB - This work aims to assess and model the behavior of both ammonium (AOB) and nitrite (NOB) oxidizing bacteria during the transition from completely anoxic to aerobic conditions. An enhanced aerobically grown culture containing AOB and NOB was subjected to anoxic conditions of varying durations from 1.5 to 12 h before its exposure to aerobic conditions. Experiments were carried out in both continuously stirred tank reactor (CSTR) and batch type reactors. Although the AOB did not exhibit any impact in their performance following the anoxic disturbance, the NOB were seriously inhibited presenting a period of reduced growth rate, which was proportional to the duration of the disturbance. This finding proves the previously postulated mechanism (NOB inhibition under periodic aerobic/anoxic operation) for achieving nitrogen removal via the partial nitrification/denitrification (PND) process as demonstrated in lab- and pilot scale operating conditions. A mathematical model was developed to describe with sufficient accuracy the performance of AOB and NOB under aerobic, anoxic, and transient conditions in both CSTR and batch type systems. The model is able to describe the inhibitory effect of anoxic exposure to NOB by assuming enzyme deactivation (under anoxic conditions) and reactivation (adjustment of the NOB enzymatic mechanism) under aerobic conditions. The presented kinetic model is quite simple and general and therefore may be used for predicting the performance of mixed growth biological systems operating via the PND process. PMID- 20583805 TI - Antibacterial activity of nanosilver ions and particles. AB - The antibacterial activity of nanosilver against Gram negative Escherichia coli bacteria is investigated by immobilizing nanosilver on nanostructured silica particles and closely controlling Ag content and size. These Ag/SiO(2) nanoparticles were characterized by S/TEM, EDX spectroscopy, X-ray diffraction the exposed Ag surface area was measured qualitatively by O(2) chemisorption. Furthermore, the fraction of dissolved nanosilver was determined by measuring the released (leached) Ag(+) ion concentration in aqueous suspensions of such Ag/SiO(2) particles. The antibacterial effect of Ag(+) ions was distinguished from that of nanosilver particles by monitoring the growth of E. coli populations in the presence and absence of Ag/SiO(2) particles. The antibacterial activity of nanosilver was dominated by Ag(+) ions when fine Ag nanoparticles (less than about 10 nm in average diameter) were employed that release high concentrations of Ag(+) ions. In contrast, when relatively larger Ag nanoparticles were used, the concentration of the released Ag(+) ions was lower. Then the antibacterial activity of the released Ag(+) ions and nanosilver particles was comparable. PMID- 20583806 TI - Binary probes for nucleic acid analysis. PMID- 20583807 TI - Trace analysis of bromate in potato snacks using high-performance liquid chromatography-tandem mass spectrometry. AB - A simple, sensitive, and selective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method in the negative-ion electrospray ionization (ESI(-)) mode was validated for the quantitation of bromate (BrO(3)(-)) in potato snacks. Ground snack specimens ( approximately 0.5 g/sample) are spiked with Br(18)O(3)(-), stable-isotope labeled bromate internal standard (IS), and vortexed with a mixture of distilled/deionized water (dd water) and heptane. Subsequently, the specimens are centrifuged, and a small portion of the aqueous extract is isolated, diluted with dd water (1:4), and analyzed by HPLC-MS/MS. The methodology has a quantitation range of 10-1000 ppb, an accuracy of 1.5-7.5%, and a precision of 5.2-13.4% across the concentration range. PMID- 20583808 TI - Relationship between lipid peroxidation and antioxidant status in the muscle of German Holstein bulls Fed n-3 and n-6 PUFA-enriched diets. AB - This study evaluated the influence of different n-3 and n-6 PUFA-enriched diets on the relationship between lipid peroxidation and antioxidant status by analyzing fatty acids (FA), lipid peroxidation, antioxidant capacity (AOC), antioxidant enzymes, trace elements, and fat-soluble vitamins in the longissimus muscle. Diet caused significant changes in muscle FA composition, leading to accumulation of beneficial n-3 FA. beta-Carotene and catalase activity were significantly elevated in muscle of the n-3 PUFA-enriched diet group compared to the n-6 PUFA-enriched diet group. Lipid peroxidation was higher in muscle of the n-3 PUFA-enriched diet group after 15 min of reaction time. There was no significant effect of diet on AOC, but it increased with reaction time. The present results suggest that the antioxidant defense in muscle of the n-3 PUFA enriched diet group could balance reactive substances under low oxidative conditions. However, the antioxidant capacity was not sufficient under abundant accumulation of reactive substances. PMID- 20583809 TI - Hydrogen molecules inside fullerene C70: quantum dynamics, energetics, maximum occupancy, and comparison with C60. AB - Recent synthesis of the endohedral complexes of C(70) and its open-cage derivative with one and two H(2) molecules has opened the path for experimental and theoretical investigations of the unique dynamic, spectroscopic, and other properties of systems with multiple hydrogen molecules confined inside a nanoscale cavity. Here we report a rigorous theoretical study of the dynamics of the coupled translational and rotational motions of H(2) molecules in C(70) and C(60), which are highly quantum mechanical. Diffusion Monte Carlo (DMC) calculations were performed for up to three para-H(2) (p-H(2)) molecules encapsulated in C(70) and for one and two p-H(2) molecules inside C(60). These calculations provide a quantitative description of the ground-state properties, energetics, and the translation-rotation (T-R) zero-point energies (ZPEs) of the nanoconfined p-H(2) molecules and of the spatial distribution of two p-H(2) molecules in the cavity of C(70). The energy of the global minimum on the intermolecular potential energy surface (PES) is negative for one and two H(2) molecules in C(70) but has a high positive value when the third H(2) is added, implying that at most two H(2) molecules can be stabilized inside C(70). By the same criterion, in the case of C(60), only the endohedral complex with one H(2) molecule is energetically stable. Our results are consistent with the fact that recently both (H(2))(n)@C(70) (n = 1, 2) and H(2)@C(60) were prepared, but not (H(2))(3)@C(70) or (H(2))(2)@C(60). The ZPE of the coupled T-R motions, from the DMC calculations, grows rapidly with the number of caged p-H(2) molecules and is a significant fraction of the well depth of the intermolecular PES, 11% in the case of p-H(2)@C(70) and 52% for (p-H(2))(2)@C(70). Consequently, the T-R ZPE represents a major component of the energetics of the encapsulated H(2) molecules. The inclusion of the ZPE nearly doubles the energy by which (p H(2))(3)@C(70) is destabilized and increases by 66% the energetic destabilization of (p-H(2))(2)@C(60). For these reasons, the T-R ZPE has to be calculated accurately and taken into account for reliable theoretical predictions regarding the stability of the endohedral fullerene complexes with hydrogen molecules and their maximum H(2) content. PMID- 20583810 TI - Structure, dynamics, and energetics of siRNA-cationic vector complexation: a molecular dynamics study. AB - The design and synthesis of safe and efficient nonviral vectors for gene delivery has attracted significant attention in recent years. Previous experiments have revealed that the charge density of a polycation (the carrier) plays a crucial role in complexation and the release of the gene from the complex in the cytosol. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with six cationic carrier systems of varying charge and surface topology. The simulations reveal detailed molecular-level pictures of the structures and dynamics of the RNA-polycation complexes. Estimates for the binding free energy indicate that electrostatic contributions are dominant followed by van der Waals interactions. The binding free energy between the 8(+)polymers and the RNA is found to be larger than that of the 4(+)polymers, in general agreement with previously published data. Because reliable binding free energies provide an effective index of the ability of the polycationic carrier to bind the nucleic acid and also carry implications for the process of gene release within the cytosol, these novel simulations have the potential to provide us with a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance the rational design of nonviral gene delivery systems. PMID- 20583811 TI - Mechanism of reductive decomposition of pentachlorophenol by Ti-doped beta Bi(2)O(3) under visible light irradiation. AB - The reductive decomposition of pentachlorophenol (PCP) by photocatalysis with Ti doped beta-Bi(2)O(3) was investigated under visible light (lambda > 420 nm) irradiation. The results indicated that hydroxyl radical (*OH) and singlet oxygen ((1)O(2)) could not be detected with electron spin resonance (ESR) on the photocatalyst under light irradiation. An electron scavenger weakened the photocatalytic activity of the photocatalyst for the decomposition of PCP; however, scavengers of reactive oxygen species (ROS) enhanced the activity. The decomposition intermediates of PCP detected by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) suggested the existence of phenol, cyclohexanone, cyclohexanol, glycol, and propylene. All the evidence suggested that reductive dechlorination was the major route in the decomposition of PCP, during which the photogenerated electron under visible light irradiation acted as reductant. The reliability of the proposed reductive mechanism was further verified by comparing the reduction potential (E(re)) of PCP with the conduction band potential (E(cb)) of the photocatalyst. The decomposition pathway of PCP with electron reduction under visible light irradiation was also investigated. PMID- 20583812 TI - Degradation of organic pollutants in a photoelectrocatalytic system enhanced by a microbial fuel cell. AB - Photocatalytic oxidation mediated by TiO(2) is a promising oxidation process for degradation of organic pollutants, but suffers from the decreased photocatalytic efficiency attributed to the recombination of photogenerated electrons and holes. Thus, a cost-effective supply of external electrons is an effective way to elevate the photocatalytic efficiency. Here we report a novel bioelectrochemical system to effectively reduce p-nitrophenol as a model organic pollutant with utilization of the energy derived from a microbial fuel cell. In such a system, there is a synergetic effect between the electrochemical and photocatalytic oxidation processes. Kinetic analysis shows that the system exhibits a more rapid p-nitrophenol degradation at a rate two times the sum of rates by the individual photocatalytic and electrochemical methods. The system performance is influenced by both external resistor and electrolyte concentration. Either a lower external resistor or a lower electrolyte concentration results in a higher p-nitrophenol degradation rate. This system has a potential for the effective degradation of refractory organic pollutants and provides a new way for utilization of the energy generated from conversion of organic wastes by microbial fuel cells. PMID- 20583814 TI - Thermoresponsive hydrogel as a delivery scaffold for transfected rat mesenchymal stem cells. AB - The concept of stem cells as a therapeutic agent has been gaining momentum. A common mode of administration of these cells is by direct injection into the target tissue. This can result in many of the cells being lost due to reflux from the injection site leading to a local loss of implanted cells. PoligoGel is a nontoxic hydrogel with an LCST near body temperature. It is also shown to be nontoxic to multiple cell types, and in the case of rat mesenchymal stem cells does not alter their differentiative capacity, either by inducing differentiation, or limiting the potential for subsequent differentiation after removal from the gel. Embedding cells in PoligoGel also does not interfere with the cells' ability to delivery therapeutic growth factors post transfection with plasmid DNA. Here a thermoresponsive hydrogel, PoligoGel, is shown to have potential to act as a scaffold for the retention of cells at an injection site, mitigating migration or washing of the cells away from the target site after implantation. PMID- 20583815 TI - Specific detection of gastric alpha-antitrypsin by immobilized trypsin on polyHEMA films. AB - Early diagnosis of gastric carcinoma is crucial for maximizing medical treatment efficacy. For the purpose of real time diagnosis ("virtual biopsy") of stomach malignancy we developed a polyHEMA platform capable of capturing human alpha1 antitrypsin precursor (A1AT); a model proteinaceous luminal biomarker. Its specific attachment to the polymeric platform was accomplished by immobilized trypsin, which was linked to the surface of the polyHEMA film by a series of PEG based spacers. Recognition was enabled by adapting an ELISA-like methodology, using rabbit anti-A1AT and HRP-conjugated anti-rabbit IgG as a secondary antibody. Since this A1AT-sensing platform was designed to be detected by endoscopic means such as a video capsule, its physical stability was tested after casting on top of a polycarbonate surface. It was found that, in contrast to classical ELISA analysis performed on polystyrene plates, A1AT detection was possible only when spacer arms were used to immobilize the capturing moiety, trypsin, with a 7-fold increase in the optical signal and a saturation kinetics dependency upon the concentration of the A1AT biomarker. PMID- 20583817 TI - Greasing their way: lipid modifications determine protein association with membrane rafts. AB - Increasing evidence suggests that biological membranes can be laterally subdivided into domains enriched in specific lipid and protein components and that these domains may be involved in the regulation of a number of vital cellular processes. An example is membrane rafts, which are lipid-mediated domains dependent on preferential association between sterols and sphingolipids and inclusive of a specific subset of membrane proteins. While the lipid and protein composition of rafts has been extensively characterized, the structural details determining protein partitioning to these domains remain unresolved. Here, we review evidence suggesting that post-translation modification by saturated lipids recruits both peripheral and transmembrane proteins to rafts, while short, unsaturated, and/or branched hydrocarbon chains prevent raft association. The most widely studied group of raft-associated proteins are glycophosphatidylinositol-anchored proteins (GPI-AP), and we review a variety of evidence supporting raft-association of these saturated lipid-anchored extracellular peripheral proteins. For transmembrane and intracellular peripheral proteins, S-acylation with saturated fatty acids mediates raft partitioning, and the dynamic nature of this modification presents an exciting possibility of enzymatically regulated raft association. The other common lipid modifications, that is, prenylation and myristoylation, are discussed in light of their likely role in targeting proteins to nonraft membrane regions. Finally, although the association between raft affinity and lipid modification is well-characterized, we discuss several open questions regarding regulation and remodeling of these post-translational modifications as well as their role in transbilayer coupling of membrane domains. PMID- 20583816 TI - Multicolor monitoring of dysregulated protein kinases in chronic myelogenous leukemia. AB - The Bcr-Abl and Lyn protein tyrosine kinases have been separately linked to the emergence of imatinib resistance in patients with chronic myelogenous leukemia. We have developed fluorescent sensors for these kinases that are enzymatically and photophysically distinct, allowing us to simultaneously, yet separately, visualize the tyrosine kinase activities of both Abl and Lyn. Multicolor monitoring revealed that an imatinib-resistant cell line (MYL-R) displays a remarkable 13-fold enhancement in Lyn kinase activity relative to its imatinib sensitive counterpart (MYL). By contrast, both cell lines display nearly identical Abl activities. The upregulation of Lyn kinase phosphotransferase activity in MYL-R cells is linked to an overexpression of the Lyn B isoform. Furthermore, MYL-R cells possess a 4-fold higher level of activated Lyn and 5 fold lower level of autoinhibited Lyn than MYL cells. Finally, studies with an activating SH2 ligand revealed that Lyn from imatinib-resistant MYL-R cells is primed and active, whereas Lyn from imatinib-sensitive cells is dependent upon phosphorylated SH2 ligands for activity. PMID- 20583818 TI - Intermittent contact-scanning electrochemical microscopy (IC-SECM): a new approach for tip positioning and simultaneous imaging of interfacial topography and activity. AB - A new scanning electrochemical microscopy (SECM) tip positioning method that allows surface topography and activity to be resolved simultaneously and independently is presented. The tip, controlled by a piezoelectric positioner operated in closed loop, is oscillated normal to the substrate surface. Changes in the oscillation amplitude, caused by the intermittent contact (IC) of the tip with the substrate surface, are used as a feedback signal to control the tip height. The method is illustrated with amperometric feedback approach curve measurements to inert (insulating) and active (conducting) substrates using 12.5 and 1 microm radii Pt disk electrodes. Imaging of gold bands on a glass substrate demonstrates the capabilities for simultaneous topography and activity mapping. The prospect for using IC methodology more widely with other types of tips is highlighted briefly. PMID- 20583819 TI - Effects of counter anions on intense photoluminescence of 1-D chain gold(I) complexes. AB - A series of cationic carbene complexes of Au(I) with different types of counteranions, [Au{C(OMe)NHMe}(2)](+)(X(-)) (X(-) = CF(3)SO(3)(-), PF(6)(-), CF(3)CO(2)(-), ClO(4)(-), and I(-)), was synthesized, and their intense photoluminescence was studied. These complexes crystallize in the same space group, and the X-ray crystallographic data of these samples revealed the short Au(I)-Au(I) aurophilic distances (3.263-3.335 A), where planar carbene Au(I) complexes are organized into linear stacks. The aurophilic Au(I)-Au(I) interactions found in the crystalline state give rise to phosphorescence with relatively high emission quantum efficiencies, whereas [Au{C(OMe)NHMe}(2)](+)(X( )) complexes show no appreciable emission in solutions. The Au(I)-Au(I) distances in the crystal of [Au{C(OMe)NHMe}(2)](+)(X(-)) vary depending on the type of counteranions because the carbene ligands of Au(I) cations are linked through hydrogen bonds with adjacent counteranions. The effects of counteranions on the Au(I)-Au(I) aurophilic interactions allow one to modulate the intense photoluminescence color from blue to yellow by adjusting the counteranions of [Au{C(OMe)NHMe}(2)](+)(X(-)) complexes. PMID- 20583820 TI - Ionic memcapacitive effects in nanopores. AB - Using molecular dynamics simulations, we show that, when subject to a periodic external electric field, a nanopore in ionic solution acts as a capacitor with memory (memcapacitor) at various frequencies and strengths of the electric field. Most importantly, the hysteresis loop of this memcapacitor shows both negative and diverging capacitance as a function of the voltage. The origin of this effect stems from the slow polarizability of the ionic solution due to the finite mobility of ions in water. We develop a microscopic quantitative model which captures the main features we observe in the simulations and suggest experimental tests of our predictions. We also suggest a possible memory mechanism due to the transport of ions through the nanopore itself, which may be observed at small frequencies. These effects may be important both in DNA sequencing proposals using nanopores and possibly in the dynamics of action potentials in neurons. PMID- 20583821 TI - Photopatternable quantum dots forming quasi-ordered arrays. AB - We have functionalized core-shell CdSe/ZnS quantum dots (QDs) with a photosensitive monolayer, rendering them solution processable and photopatternable. Upon exposure to ultraviolet radiation, films composed of this material were found to polymerize, forming interconnected arrays of QDs. The photoluminescence properties of the nanocrystal films increased with photocuring. The material was found to be suitable for spin casting and was used as the active layer in a green electroluminescent device. The electroluminescence efficiency of devices containing a photocured active layer was found to be largely enhanced when compared to devices containing nonphotocured active layers. The material also showed excellent adhesion to both organic and inorganic substrates because of the unique combination of a siloxane and a photopatternable layer as ligands. The pristine functionalized nanocrystals could easily be used for two-dimensional patterning on organic and inorganic substrates. The photopatternable quantum dots were uniformly dispersed into a photopolymerizable resin to fabricate QD embedded three-dimensional microstructures. PMID- 20583822 TI - Proteomics analysis of distinct portal vein tumor thrombi in hepatocellular carcinoma patients. AB - Portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is known as a major complication associated with poor survival. We clinically defined a type of distinct PVTT (dPVTT) in small HCC patients that is distant to liver parenchyma tumor (PT). The biological features of dPVTT are not clear. We utilized two-dimensional electrophoresis and tandem MS to compare and identify differentially expressed proteins between dPVTT and PT tissues. Of the 65 spots identified as differentially expressed (p < 0.05) between the two cancerous tissues, 19 (corresponding to 19 unique proteins) were identified. Further analysis of five proteins confirmed quantitative differences between the two tumor tissues. Upon comparison with PT tissues of HCC, c-kit was also significantly upregulated in dPVTTs in small HCC patients and the CSQT-2 cell line derived from dPVTT tissues, which validated the differences between the dPVTT and PT tissues. The protein expression profiles and proteins identified in this study demonstrate the presence of dPVTTs with more malignant phenotypes and will be useful in clarifying the mechanisms through which dPVTT develops. Specific treatments targeting dPVTT might be applied to HCC patients with dPVTT. PMID- 20583824 TI - Green predictions. PMID- 20583823 TI - Small-molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry. AB - Post-translational modifications on histones are an important mechanism for the regulation of gene expression and are involved in all aspects of cell growth and differentiation, as well as pathological processes including neurodegeneration, autoimmunity, and cancer. A major challenge within the chromatin field is to develop methods for the quantitative analysis of histone modifications. Here we report a mass spectrometry (MS) approach based on ultraperformance liquid chromatography high/low collision switching (UPLC-MS(E)) to monitor histone modifications in cells. This approach is exemplified by the analysis of trimethylated lysine-9 levels in histone H3, following a simple chemical derivatization procedure with d(6)-acetic anhydride. This method was used to study the inhibition of histone demethylases with pyridine-2,4-dicarboxylic acid (PDCA) derivatives in cells. Our results show that the PDCA-dimethyl ester inhibits JMJD2A catalyzed demethylation of lysine-9 on histone H3 in human HEK 293T cells. Demethylase inhibition, as observed by MS analyses, was supported by immunoblotting with modification-specific antibodies. The results demonstrate that PDCA derived small molecules are cell permeable demethylase inhibitors and reveal that quantitative MS is a useful tool for measuring post-translational histone modifications in cells. PMID- 20583825 TI - Delivering sustainable infrastructure that supports the urban built environment. AB - Sustainable living will require megacity-level infrastructural support designs and paradigms. PMID- 20583826 TI - Toxicological mixture models are based on inadequate assumptions. PMID- 20583827 TI - Potential implications for monitoring serum bile acid profiles in circulation with serum proteome for carbon tetrachloride-induced liver injury/regeneration model in mice. AB - Bile acids have recently emerged as versatile signaling molecules, and their signaling pathway is a promising target for the treatment of metabolic diseases. Here, we developed a highly sensitive and high-throughput quantification method for six taurine- and glycine-conjugated bile acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry after solid-phase extraction (SPE-MALDI-TOF MS). In a carbon tetrachloride (CCl4)-induced liver injury/regeneration model in mice, serum bile acid profiles were monitored, and the same samples were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and protein spots that significantly changed in quantity in a serial time points were identified by MALDI-TOF MS. Serum taurocholic acid (TCA) concentration was significantly elevated earlier than the increase of serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activity, a potentially sensitive marker for minimal hepatic damage. Furthermore, TCA peaked at 20 h after treatment when massive serum proteins appeared in circulation. It should be noted that direct MALDI-imaging mass spectrometry (IMS) has succeeded in showing a hepatic lobular distribution change of TCA, predominantly seen in zone 1 area whereas necrotic changes were dominant in zone 3 area. The in-depth analysis of bile acid profiles in circulation with hepatic lobular distribution is a strong basis to understand the serum proteome in CCl4 induced liver injury model. PMID- 20583829 TI - Molecular-scale investigations of cellulose microstructure during enzymatic hydrolysis. AB - Changes in cellulose microstructure have been proposed to occur throughout hydrolysis that impact enzyme access and hydrolysis rates. However, there are very few direct observations of such changes in ongoing reactions. In this study, changes in the microstructure of cellulose are measured by simultaneous confocal and atomic force microscopy and are correlated to hydrolysis extents and quantities of bound enzyme in the reaction. Minimally processed and never-dried cellulose I was hydrolyzed by a purified cellobiohydrolase, Trichoderma reesei Cel7A. Early in the reaction ( approximately 30% hydrolysis), at high hydrolysis rates and high bound cellulase quantities, untwisting of cellulose microfibrils was observed. As the hydrolysis reaction neared completion (>80% hydrolysis), extensively thinned microfibrils (diameters of 3-5 nm) and channels (0.3-0.6 nm deep) along the lengths of the microfibrils were observed. The prominent microstructural changes in cellulose due to cellobiohydrolase action are discussed in the context of the overall hydrolysis reaction. PMID- 20583828 TI - Near-infrared fluorescent probe for imaging of pancreatic beta cells. AB - The ability to image and ultimately quantitate beta-cell mass in vivo will likely have far reaching implications in the study of diabetes biology, in the monitoring of disease progression or response to treatment, and for drug development. Here, using animal models, we report on the synthesis, characterization, and intravital microscopic imaging properties of a near infrared fluorescent exendin-4 analogue with specificity for the GLP-1 receptor on beta cells (E4(K12)-Fl). The agent demonstrated subnanomolar EC(50) binding concentrations, with high specificity and binding that could be inhibited by GLP 1R agonists. Following intravenous administration to mice, pancreatic islets were readily distinguishable from exocrine pancreas, achieving target-to-background ratios within the pancreas of 6:1, as measured by intravital microscopy. Serial imaging revealed rapid accumulation kinetics (with initial signal within the islets detectable within 3 min and peak fluorescence within 20 min of injection), making this an ideal agent for in vivo imaging. PMID- 20583830 TI - New method and detection of high concentrations of monomethylarsonous acid detected in contaminated groundwater. AB - Monomethylarsonous acid (MMAIII) was detected in groundwater from a former herbicide production plant in the USA. The site has total arsenic concentrations up to thousands of mg/L, representing one of the most severe cases of arsenic contamination ever reported. Structure-specific detection of MMAIII, along with arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV), was achieved using liquid chromatography separation with electrospray ionization tandem mass spectrometry detection (HPLC-ESI-MS/MS). To enable the electrospray of MMAIII and AsIII, dimercaptosuccinic acid (DMSA) was used to derivatize these trivalent arsenicals online, so that their complexes with DMSA could be detected using negative ionization ESI-MS/MS. The presence of MMAIII was verified using high resolution mass spectrometry to measure accurate mass, tandem mass spectrometry to monitor fragmentation, and three different separation techniques to resolve arsenic species. The measured accurate mass of the suspected MMAIII compound in a groundwater sample was 122.9607+/-0.0003 amu, which was in good agreement with the theoretical value and that of the MMAIII standard. Simultaneous monitoring of AsO+ at m/z 91 and SO+ at m/z 48 using HPLC ICPMS operating in dynamic reaction cell mode ruled out possible confounding from any sulfur-containing arsenic compound. The concentrations of MMAIII found in the groundwater samples from a contaminated site were as high as 3.9-274 mg/L, the highest ever observed in the environment. PMID- 20583831 TI - Photocontrolled compound release system using caged antimicrobial peptide. AB - A novel photocontrolled compound release system using liposomes and a caged antimicrobial peptide was developed. The caged antimicrobial peptide was activated by UV irradiation, resulting in the formation of pores on the liposome surface to release the contained fluorophores. The compound release could be observed using fluorescence measurements and time-lapse fluorescence microscopy. UV irradiation resulted in a quick release of the inclusion compounds (within 1 min in most cases) under simulated physiological conditions. The proposed system is expected to be applicable in a wide range of fields from cell biology to clinical sciences. PMID- 20583832 TI - Microsecond dye regeneration kinetics in efficient solid state dye-sensitized solar cells using a photoelectrochemically deposited PEDOT hole conductor. AB - Microsecond dye-regeneration kinetics was observed in efficient solid state dye sensitized solar cells using photoelectrochemically deposited poly(3,4 ethylenedioxythiophene (PEDOT) hole conductors using transient absorption spectroscopy. The dye-regeneration rate is orders of magnitude slower than the case using the I(-)/I(3)(-) redox couple or commonly used small molecule hole conductor and is attributed to the low dye to PEDOT ratio within the films. PMID- 20583833 TI - Plasmonic nanoparticle dimers for optical sensing of DNA in complex media. AB - We introduce a new sensing modality based on the actuation of discrete gold nanoparticle dimers. Binding of the target DNA leads to a geometrical extension of the dimer, thereby yielding a spectral blue shift in the hybridized plasmon mode as detected by single nanostructure scattering spectroscopy. The magnitude and opposite direction of this shift enabled us to spectroscopically distinguish the target from nonspecific binding and to detect the target in complex media like serum. PMID- 20583834 TI - Rapid acquisition of multidimensional solid-state NMR spectra of proteins facilitated by covalently bound paramagnetic tags. AB - We describe a condensed data collection approach that facilitates rapid acquisition of multidimensional magic-angle spinning solid-state nuclear magnetic resonance (SSNMR) spectra of proteins by combining rapid sample spinning, optimized low-power radio frequency pulse schemes and covalently attached paramagnetic tags to enhance protein (1)H spin-lattice relaxation. Using EDTA Cu(2+)-modified K28C and N8C mutants of the B1 immunoglobulin binding domain of protein G as models, we demonstrate that high resolution and sensitivity 2D and 3D SSNMR chemical shift correlation spectra can be recorded in as little as several minutes and several hours, respectively, for samples containing approximately 0.1-0.2 micromol of (13)C,(15)N- or (2)H,(13)C,(15)N-labeled protein. This mode of data acquisition is naturally suited toward the structural SSNMR studies of paramagnetic proteins, for which the typical (1)H longitudinal relaxation time constants are inherently a factor of at least approximately 3-4 lower relative to their diamagnetic counterparts. To illustrate this, we demonstrate the rapid site-specific determination of backbone amide (15)N longitudinal paramagnetic relaxation enhancements using a pseudo-3D SSNMR experiment based on (15)N-(13)C correlation spectroscopy, and we show that such measurements yield valuable long-range (15)N-Cu(2+) distance restraints which report on the three-dimensional protein fold. PMID- 20583835 TI - Asymmetric vinylogous aldol reaction of silyloxy furans with a chiral organic salt. AB - Despite their synthetic significance there is a general lack of asymmetric vinylogous aldol reactions that tolerate variations of both the silyloxy furans and aldehydes. We have developed a new chiral organic catalyst based on a carboxylate-ammonium salt prepared from a thiourea-amine and a carboxylic acid. This new catalyst enabled us to develop an efficient asymmetric vinylogous aldol reaction of unprecedented scope with respect to both 2-trimethylsilyloxy furans and aldehydes. PMID- 20583837 TI - Polyphenylene-based materials for organic photovoltaics. PMID- 20583839 TI - Transmetalation is the rate-limiting step: quantitative kinetic investigation of nickel-catalyzed oxidative coupling of arylzinc reagents. AB - Transmetalation is the rate-limiting step! The transmetalation between arylzinc reagents and ArNi(II)R was confirmed as the rate-limiting step in the nickel catalyzed oxidative coupling reactions. It was proved to be an excellent model allowing the first quantitative measurement of the kinetic rate constants of transmetalation from a live catalytic system. Rate constants from 0.04 to 0.31 M( 1) s(-1) were obtained for different arylzinc reagents under the conditions, and the activation enthalpy DeltaH(++) was 14.6 kcal/mol for PhZnCl. The substituent effect on the transmetalation was also gained for the first time from the catalytic reaction. PMID- 20583840 TI - Quantitative determination of interactions between tannic acid and a model protein using diffusion and precipitation assays on cellulose membranes. AB - Astringency perception has been associated with interactions between tannins present in some foods and salivary proteins. A variety of laboratory methods to measure tannin-protein interactions have been designed. Most of them, however, do not differentiate clearly between tannins and the protein fraction. The aim of this work was to characterize a method to measure tannin-protein interactions by following the behavior of the protein fraction. Experiments were performed with a representative hydrophilic globular protein, bovine serum albumin (BSA), and a gallotannin-rich commercial product, tannic acid (TA). Using cellulose membranes, concentration dependency of the inhibitory effect of TA upon the diffusion of BSA on the membrane and the ability of TA to precipitate BSA were assayed. Selective staining of the protein fraction was obtained using Coomassie Blue. TA inhibited BSA diffusion in a concentration-dependent manner in the range from a 0.1-0.2 up to a 1 microg of TA/microg of BSA ratio. Likewise, maximal precipitation of BSA (equivalence point) occurred at a 0.55 microg of TA/microg of BSA ratio, that is, when about 36 representative molecules of TA (average molecular weight = 1000) interact with every molecule of BSA (molecular weight = 66, 000). The procedure may be readily adapted to measure interactions between different types of tannins and proteins that may be of relevance for taking decisions during food manufacturing. PMID- 20583841 TI - Thorough study of reactivity of various compound classes toward the Folin Ciocalteu reagent. AB - A thorough study was done to test the reactivity of the Folin-Ciocalteu (F-C) reagent toward various compound classes. Over 80 compounds were tested. Compound classes included phenols, thiols, vitamins, amino acids, proteins, nucleotide bases, unsaturated fatty acids, carbohydrates, organic acids, inorganic ions, metal complexes, aldehydes, and ketones. All phenols, proteins, and thiols tested were reactive toward the reagent. Many vitamin derivatives were also reactive, as were the inorganic ions Fe(+2), Mn(2+), I(-), and SO(3)(2-). Other compounds showing reactivity included the nucleotide base guanine and the trioses glyceraldehyde and dihydroxyacetone. Copper complexation enhanced the reactivity of salicylate derivatives toward the reagent, whereas zinc complexation did not. Several amino acids and sugars that were reported to be reactive toward the F-C reagent in earlier studies were found not to be reactive in this study, at least in the concentrations used. Reaction kinetics of each compound with the F-C reagent were also measured. Most compounds tested showed a biphasic kinetic pattern with half-lives under 1 min. Trolox and ascorbic acid displayed a rapid monophasic pattern in which the reaction reached end point within 1 min. In summary, this study has shown that the F-C reagent is significantly reactive toward other compounds besides phenols. As other investigators have suggested, the F-C assay should be seen as a measure of total antioxidant capacity rather than phenolic content. Because phenolics are the most abundant antioxidants in most plants, it gives a rough approximation of total phenolic content in most cases. PMID- 20583842 TI - Isolation, characterization, and immunological effects of alpha-galacto oligosaccharides from a new source, the herb Lycopus lucidus Turcz. AB - This study was designed to isolate and characterize a mixture of alpha-galacto oligosaccharides (GOS) from a new source, the roots of Lycopus lucidus Turcz. (RL), a traditional dietary treatment. In this study, the chemical components and immunological function of RL-GOS were investigated. HPLC analysis showed that the purified RL-GOS was a typical raffinose family oligosaccharide (RFO) with a high stachyose content of 51.8% (w/w), followed by 26.5% raffinose and 10.1% verbascose. Further functional evaluation showed that RL-GOS could elicit a significant increase (p < 0.05 vs control) in humoral immunity, as measured by plaque-forming cell (PFC) generation and serum hemolysin level in response to sheep red blood cells (SRBC) at all three tested doses of RL-GOS (0.75, 1.5, and 3.0 g/kg of BW) in mice. In addition, the cellular immune activity of RL-GOS was also demonstrated by enhancing in vivo delayed-type hypersensitivity (DTH) reaction to SRBC and spleenocyte proliferation response to concanavalin A (p < 0.05, compared with control group). Nevertheless, there were no significant differences in weight gain, lymphoid organ indices, and phagocytosis capacity following RL-GOS treatment. This study provides evidence for the discovery of a new GOS source (20% w/w GOS in fresh roots of L. lucidus Turcz.) and its potential application as an immune stimulant in functional foods. PMID- 20583843 TI - Searching for early signs of pancreatic cancer. PMID- 20583844 TI - 1-(5-carboxyindol-1-yl)propan-2-one inhibitors of human cytosolic phospholipase A(2)alpha with reduced lipophilicity: synthesis, biological activity, metabolic stability, solubility, bioavailability, and topical in vivo activity. AB - Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent inhibitors of human cytosolic phospholipase A(2)alpha (cPLA(2)alpha). In continuation of our attempts to develop clinical active cPLA(2)alpha inhibitors, a series of structurally related indole-5 carboxylic acids with reduced lipophilicity was synthesized and tested for cPLA(2)alpha-inhibitory potency. Furthermore, the thermodynamic solubility of these compounds and their metabolic stability in rat liver microsomes were evaluated. With an IC(50) of 0.012 microM against the isolated enzyme, compound 36 was one of the most potent cPLA(2)alpha inhibitors that emerged during the structure-activity relationship study. Concomitantly, 36 possessed the highest water solubility (212 microg/mL at pH 7.4) of all new target compounds. Despite these favorable properties, peroral application of 36 (100 mg/kg) in mice only led to low concentrations of the substance in blood plasma. A very high plasma clearance was observed after intravenous administration of 36 (10 mg/kg). However, in a topical murine model of contact dermatitis, 36 showed a pronounced anti-inflammatory in vivo activity. PMID- 20583845 TI - Dihydrogen activation by antiaromatic pentaarylboroles. AB - Facile metal-free splitting of molecular hydrogen (H(2)) is crucial for the utilization of H(2) without the need for toxic transition-metal-based catalysts. Frustrated Lewis pairs (FLPs) are a new class of hydrogen activators wherein interactions with both a Lewis acid and a Lewis base heterolytically disrupt the hydrogen-hydrogen bond. Here we describe the activation of hydrogen exclusively by a boron-based Lewis acid, perfluoropentaphenylborole. This antiaromatic compound reacts extremely rapidly with H(2) in both solution and the solid state to yield boracyclopent-3-ene products resulting from addition of hydrogen atoms to the carbons alpha to boron in the starting borole. The disruption of antiaromaticity upon reaction of the borole with H(2) provides a significant thermodynamic driving force for this new metal-free hydrogen-splitting reaction. PMID- 20583846 TI - Functionalization of peptides and proteins by Mukaiyama aldol reaction. AB - The scope of the catalyst-free water-based Mukaiyama aldol reaction was explored through its application to the site-selective functionalization of N-terminal aldehydes of peptides and proteins. Various functional groups were introduced under mild and environmentally friendly conditions, with the first demonstration of aldol C-C bond formation in protein labeling studies. The efficiency and speed achieved in protein labeling can be of special interest in chemical biology studies. PMID- 20583847 TI - Late-onset ankylosing spondylitis and spondylarthritis: an update on clinical manifestations, differential diagnosis and pharmacological therapies. AB - Ankylosing spondylitis (AS) and spondylarthritis (SpA) are generally observed in young male patients but can be diagnosed in the elderly. These cases correspond to late-onset or late-diagnosed AS or SpA. The clinical presentation may be either typical axial disease with a more severe illness compared with young-onset disease, or peripheral oligoarthritis of the lower limbs with pitting oedema (late-onset peripheral spondylarthropathy). New criteria for axial SpA including MRI-determined modifications of the sacroiliac joints may help the clinician with diagnosis. The treatment options for late-onset/-diagnosed AS include the same drugs as those taken by patients with young-onset AS, i.e. NSAIDs, sulfasalazine and anti-tumour necrosis factor (TNF)-alpha agents. Anti-TNFalpha agents are very effective drugs in young-onset AS and SpA. However, the effectiveness and safety of this drug class has not been specifically evaluated in elderly AS/SpA patients, and caution is therefore required with use of these drugs in elderly patients with co-morbidities and/or polypharmacy. In particular, careful evaluation for the risk of infection and cardiovascular events is recommended before initiating anti-TNFalpha agents in this age category. However, safety data from elderly patients with rheumatoid arthritis seem reassuring. With the increasing life expectancy and the new diagnostic modalities for axial (and peripheral) SpA, it is likely that the number of patients (diagnosed) with late onset AS/SpA will increase. Thus, the clinician must be familiar with the clinical characteristics and particularities of this group of inflammatory rheumatic diseases. PMID- 20583848 TI - Tissue-selective estrogen complexes: a promising option for the comprehensive management of menopausal symptoms. AB - At menopause many women experience undesired symptoms such as hot flashes and those associated with vulvovaginal atrophy, and are susceptible to loss of bone mass. Menopausal therapies to date include various estrogen and estrogen progestin (progesterone congener) formulations. However, both physicians and women became concerned about hormone-related therapies following publication of data from the Women's Health Initiative. Thus, the need exists for alternative therapies for postmenopausal women. Tissue-selective estrogen complexes (TSECs) are the pairing of estrogen(s) with a selective estrogen receptor modulator (SERM). The goal of developing a TSEC is to provide the clinical benefits of each of its components with improved tolerability. This goal can potentially be achieved by the result of the different molecular and cellular activities of the treatment's estrogen and SERM components. The therapeutic profile of a TSEC would optimally include relief of hot flashes, treatment of vulvovaginal atrophy and its symptoms, and prevention of bone loss, while providing safety for the endometrium and breast. Recent data indicate that the TSEC containing the SERM bazedoxifene and conjugated estrogens relieves hot flashes, improves vulvovaginal atrophy and its symptoms, and prevents loss of bone mass without stimulating the endometrium. This article reviews the current options for menopausal treatment as well as the environment that has driven the most recent evolution of new therapies for menopausal women, including the most recent development of the TSEC bazedoxifene and its early preclinical and clinical data. PMID- 20583849 TI - Optimal management of peptic ulcer disease in the elderly. AB - Recent data report that the incidence of peptic ulcer is decreasing in the general population; conversely, the rates of gastric and duodenal ulcer hospitalization and mortality remain very high in older patients. Two major factors that might explain this epidemiological feature in the elderly population are the high prevalence of Helicobacter pylori infection and the increasing prescriptions of gastroduodenal damaging drugs, including NSAIDs and/or aspirin (acetylsalicylic acid). The main goals for treating peptic ulcer disease in old age are to reduce recurrence of the disease and to prevent complications, especially bleeding and perforation. The available treatments for peptic ulcer are essentially based on gastric acid suppression with antisecretory drugs and the eradication of H. pylori infection. The aim of this article is to report the available data on clinical efficacy and tolerability of peptic ulcer treatments in elderly patients and provide recommendations for their optimal use in this special population. Proton pump inhibitor (PPI)-based triple therapies for 7 days are highly effective for the cure of H. pylori-positive peptic ulcers as well as for reducing ulcer recurrence. Antisecretory drugs are also the treatment of choice for NSAID- or aspirin-related peptic ulcers and are useful as preventive therapy in chronic users of NSAIDs and low-dose aspirin as antiplatelet therapy. Antisecretory PPI therapy has a favourable tolerability profile in geriatric patients; however, monitoring is suggested in older patients with frequent pulmonary infections, gastrointestinal malabsorption, unexplained chronic diarrhoea, osteoporosis or those taking concomitant cytochrome P450 2C19 metabolized medications. The overall approach to the geriatric patient should include a comprehensive geriatric assessment that ensures multidimensional evaluation of the patient in order to better define the clinical risk of adverse outcomes in the older patient with peptic ulcer and its complications. PMID- 20583850 TI - Potential medication problems in older newly diagnosed cancer patients in Canada during cancer treatment: a prospective pilot cohort study. AB - INTRODUCTION: Older cancer patients are possibly at an increased risk of medication-related problems because, typically, they receive many medications during their cancer treatment, both for the cancer itself and for supportive care. OBJECTIVES: The aim of this study was to describe the number and severity of potential medication problems during treatment of cancer in the first year after diagnosis. We also sought to examine whether patients receiving systemic cancer treatment had more medication-related problems at 3, 6 and 12 months than those not receiving systemic cancer treatment. METHODS: This was a prospective pilot cohort study on health and vulnerability in older newly diagnosed cancer patients with 1-year follow-up. The study was conducted at Segal Cancer Centre, Jewish General Hospital, Montreal, Canada. Of 156 eligible patients, 112 agreed to participate (response 71.8%). The patients were aged >or=65 years and were newly diagnosed with breast, colorectal or lung cancer, lymphoma or multiple myeloma. Patients were asked for permission to obtain their list of medications from their pharmacist. The cancer treatment information was abstracted from the medical chart. Vigilance Sante software was used to identify the presence, type and severity of potential medication problems. RESULTS: The median number of medications was five at baseline, seven at 3 months and six at 6 and 12 months. At baseline, 247 potential medication problems were identified, followed by 273 at 3 months, 229 at 6 months and 188 at 12 months. About half of the patients at each follow-up had one or more moderate or severe potential medication problem. Patients receiving systemic cancer treatment had significantly fewer potential problems at 3 months than patients not receiving systemic cancer treatment, but no differences were observed at 6 and 12 months. The most common warnings were contraindications, interactions and miscellaneous warnings, and the cancer treatment was involved in 12% of all potential problems. CONCLUSION: This study showed that the majority of older newly diagnosed cancer patients take prescribed medication and about two-thirds have potential medication problems, of which about half are of at least moderate severity. The cancer treatment was involved in only a small proportion of all potential drug problems. PMID- 20583851 TI - Improved blood pressure control in elderly hypertensive patients: results of the PAPY-65 Survey. AB - BACKGROUND: Blood pressure (BP) control is far from optimal. Studies on factors influencing BP control in the elderly are limited, yet identification of factors contributing to the low rate of BP control is a prerequisite to improvement of clinical management. OBJECTIVE: To evaluate the rate of BP control and the relationship between different clinical characteristics and BP control in treated hypertensive outpatients aged >or=65 years. METHODS: The PAPY-65 Survey was a prospective cross-sectional survey conducted in primary care in Belgium in 2007. Participating primary-care physicians were required to include consecutive hypertensive patients aged >or=65 years and treated with antihypertensive drugs. Demographic and anthropometric data as well as data on cardiovascular risk factors and history were obtained. BP was measured in accordance with the European Society of Hypertension/European Society of Cardiology guidelines. RESULTS: The mean +/- standard deviation (SD) age of the 1272 patients enrolled in the survey was 75 +/- 7 years; 702 (55%) patients were women. The mean +/- SD systolic/diastolic BP was 134/79 +/- 13/8 mmHg. BP was normalized (reduced to <140/90 mmHg, or <130/80 mmHg in patients with diabetes mellitus) in 617 (48.5%) patients overall and in 88 (24%) patients with diabetes (n = 371). The majority of patients (921; 72%) were treated with two or more antihypertensive drugs. Both general obesity (body mass index >or=30 vs <25 kg/m2) and abdominal obesity were associated with lack of BP control (unadjusted odds ratio [OR] 2.988, 95% CI 2.200, 4.057 and OR 2.066, 95% CI 1.649, 2.588, respectively). Abdominal obesity was no longer related to BP control when adjusted for the presence of diabetes. Diabetes was strongly associated with lack of BP control only when a stringent definition of BP control (<130/80 mmHg) was used. The combined presence of subclinical organ damage and a history of cardiovascular disease was associated with less uncontrolled BP (OR 0.62, 95% CI 0.48, 0.80). CONCLUSION: Compared with previous data in the elderly in Belgium, a clear improvement in BP control was observed, probably related to the use of more antihypertensive agents. The presence of diabetes, excess bodyweight and abdominal obesity were all associated with poor BP control. PMID- 20583852 TI - Statin prescribing in the elderly in the Netherlands: a pharmacy database time trend study. AB - INTRODUCTION: There is some evidence that the beneficial effects of HMG-CoA reductase inhibitors (statins) in the elderly are at least comparable to the effects in middle-aged people. However, several studies have shown prescription rates of statins to be significantly lower in the elderly than in younger populations. OBJECTIVE: The aim of the present study was to monitor statin prescribing trends in the elderly in the Netherlands over time in terms of prevalence, incidence, type of statin, dose prescribed and adherence to clinical guidelines. METHODS: The database of a community pharmacy in Utrecht, which includes prescription data for approximately 11,000 people, was analysed to investigate trends in statin prescriptions from January 1999 to December 2008. The 1-year prevalence and incidence of statin use stratified by age were determined for each calendar year. Rate ratios (RRs) and 95% confidence intervals were calculated with 1999 as the reference year. Furthermore, the following trends of interest were calculated for each calendar year: the percentage of statin users prescribed simvastatin or atorvastatin, the median dose of simvastatin and atorvastatin prescribed, and the percentage of simvastatin users prescribed a dosage of 40 mg/day (which is recommended by the Dutch multidisciplinary guideline). RESULTS: The 1-year prevalence of statin use in medication users aged >or=50 years increased from 13.9% in 1999 to 22.8% in 2008 (RR 1.6; 95% CI 1.4, 1.9; p < 0.001). Overall, the lowest prevalence (5.1% in 1999 and 15.2% in 2008) and incidence rates (3.2% in 2000 and 4.2% in 2008) were found in patients aged >or=80 years. Before 2006, simvastatin was the most commonly prescribed statin, but the number of users declined as the percentage of patients with new simvastatin prescriptions decreased (from 43.4% in 2000 to 36.5% in 2005) and the percentage of patients treated with new atorvastatin prescriptions increased (from 37.7% in 2000 to 47.3% in 2005). As from 2006, when the Dutch multidisciplinary guideline for Cardiovascular Risk Management was introduced, recommending treatment with a daily simvastatin dose of 40 mg, the number of simvastatin users increased again and most treatment-naive patients were started on simvastatin (62.3% in 2006, increasing to 66.7% in 2008). The median simvastatin dose increased from 10 mg in 1999 to 20 mg in 2001, remaining at the same dose until 2008, and appeared to be related to the patient's age. From 2006, patients aged >or=80 years were the least likely group to receive the recommended dose of 40 mg simvastatin daily (10.0-20.0% of simvastatin users aged >or=80 years compared with 32.5-36.9% of simvastatin users aged 60-69 years). CONCLUSION: Despite the benefits of statin treatment previously reported in older patients, the prevalence and incidence of statin use were lower in elderly patients compared with younger patients. In addition, lower dosages of statins were prescribed. These findings suggest the beneficial effects of statins in the elderly observed in clinical trials may not be achieved in everyday practice. PMID- 20583853 TI - Intanza 15 microg intradermal seasonal influenza vaccine: in older adults (aged >or=60 years). AB - Intradermal seasonal influenza vaccine delivered by a microneedle injection system (Intanza) contains inactivated split virion antigens from influenza type A (H1N1 and H3N2) and B strains as recommended annually by the WHO and the EU for the prevention of seasonal influenza. In randomized, comparator-controlled, phase III trials in elderly volunteers, Intanza 15 microg elicited a strong immune response against influenza virus. In a pivotal trial, seroprotection rates with Intanza 15 microg were significantly greater than with the intramuscular comparator vaccine Vaxigrip (primary endpoint). A strong immune response was also observed with Intanza 15 microg following second and third annual vaccinations in consecutive seasons in terms of seroprotective antibody titres for all three strains (H1N1, H3N2 and B). In another phase III trial, Intanza 15 microg was as immunogenic as the intramuscular, adjuvanted vaccine Fluad, with noninferiority established in terms of ratios of geometric mean titres against H1N1 and B strains using the haemagglutinin inhibition method and against all three strains using the single radial haemolysis method. Intanza 15 microg was generally well tolerated in clinical trials in the elderly, with the most common adverse events observed being solicited injection-site reactions. The majority of solicited injection-site reactions were mild and spontaneously resolved within 1-3 days of onset; transient, visible injection-site reactions with the intradermal route of injection are not surprising as the vaccine is injected close to the skin surface. PMID- 20583854 TI - Theoretical studies on the molecular basis of HIV-1RT/NNRTIs interactions. AB - Molecular dynamics simulations (MD) of the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complexed with the four non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz (EFV), emivirine (EMV), etravirine (ETV) and nevirapine (NVP), were performed to examine the structures, binding free energies and the importance of water molecules in the binding site. The binding free energy, calculated using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), was found to decrease in the following order: EFV ~ ETV > EMV > NVP. The decrease in stability of the HIV-1 RT/NNRTI complexes is in good agreement with the experimentally derived half maximal inhibitory concentration (IC(50)) values. The interaction energy of the protein-inhibitor complexes was found to be essentially associated with the cluster of seven hydrophobic residues, L100, V106, Y181, Y188, F227, W229 and P236, and two basic residues, K101 and K103. Moreover, these residues are considered to be the most frequently detected mutated amino acids during treatment by various NNRTIs and therefore, those most likely to have been selected in the population for resistance. PMID- 20583855 TI - Synthesis and antiproliferative activities against Hep-G2 of salicylanide derivatives: potent inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase. AB - A series of salicylanilide derivatives (compounds 1-32) were synthesised by reacting substituted salicylic acids and anilines. The chemical structures of these compounds were determined by (1)H-NMR, electrospray ionisation mass spectrometry (ESI-MS) and elemental analysis. The compounds were assayed for their antiproliferative activities against the Hep-G2 cell line by the 3-(4,5 dimethylthylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Among the compounds tested, 22 and 28 showed the most favouable antiproliferative activities with 50% inhibitory concentration (IC(50)) values of 1.7 and 1.3 MUM, respectively, which were comparable to the positive control of 5-fluorouracil (IC(50)=1.8 MUM). A solid-phase ELISA assay was also performed to evaluate the ability of compounds 1-32 to inhibit the autophosphorylation of the epidermal growth factor receptor tyrosine kinase (EGFR TK). Docking simulations of 22 and 28 were carried out to illustrate the binding mode of the molecule into the EGFR active site, and the result suggested that both compounds 22 and 28 could bind the EGFR kinase well. PMID- 20583857 TI - A facile microwave assisted green chemical synthesis of novel piperidino 2 thioxoimidazolidin-4-ones and their in vitro microbiological evaluation. AB - A series of novel hybrid heterocyclic compounds, 3-(3-alkyl-2,6-diarylpiperin-4 ylidene)-2-thioxoimidazolidin-4-ones were synthesised and a comparative study was also carried out under microwave irradiation. The synthesised compounds were characterised by their melting points, elemental analysis, MS, FT-IR, one dimensional NMR (1H, D(2)O exchanged 1H and (13)C), two dimensional HOMOCOSY and NOESY spectroscopic data. All the synthesised title compounds were screened for their in vitro antibacterial and antifungal activity against clinically isolated strains namely B. subtilis, M. luteus, S. typhii, S. paratyphii B, S. felxneri, P. vulgaris, A. niger, Mucor, Rhizopus and M. gypsuem and the results were discussed. PMID- 20583856 TI - Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations. AB - Nantenine, as well as a number of flexible analogs, were evaluated for acetylcholinesterase (AChE) inhibitory activity in microplate spectrophotometric assays based on Ellman's method. It was found that the rigid aporphine core of nantenine is an important structural requirement for its anticholinesterase activity. Nantenine showed mixed inhibition kinetics in enzyme assays. Molecular docking experiments suggest that nantenine binds preferentially to the catalytic site of AChE but is also capable of interacting with the peripheral anionic site (PAS) of the enzyme, thus accounting for its mixed inhibition profile. The aporphine core of nantenine may thus be a useful template for the design of novel PAS or dual-site AChE inhibitors. Inhibiting the PAS is desirable for prevention of aggregation of the amyloid peptide Abeta, a major causative factor in the progression of Alzheimer's disease (AD). PMID- 20583858 TI - Substituted benzenediol Schiff bases as promising new anti-glycation agents. AB - A feature of diabetes is that the rate of protein glycation and the formation of advanced glycation endproducts (AGEs) increases spontaneously due to the abnormally elevated levels of sugar in the blood. The glycation of proteins is associated with a large number of late diabetic complications (retinopathy, neuropathy, atherosclerosis, end stage renal diseases, rheumatoid arthritis and neurodegenerative diseases). The increase in diabetic complications is a major cause of morbidity and mortality, which has increased significantly in the last two decades. Therefore, there is a considerable recent interest in the identification of lead molecules, which can inhibit the glycation process or slow it down considerably. A new class of anti-glycation agents has been identified, based on the spectrofluorimetric analysis of fluorescent advanced glycation endproducts (AGEs), benzenediol Schiff bases, and their structure-activity relationships have been studied. Some of these compounds have shown a promising anti-glycation potential in vitro. PMID- 20583859 TI - Pharmacological significance of triazole scaffold. AB - The triazole nucleus is one of the most important and well known heterocycles which is a common and integral feature of a variety of natural products and medicinal agents. Triazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, antihypertensive, antimalarial, local anaesthetic, antianxiety, antidepressant, antihistaminic, antioxidant, antitubercular, anti-Parkinson's, antidiabetic, antiobesity and immunomodulatory agents, etc. The broad and potent activity of triazole and their derivatives has established them as pharmacologically significant scaffolds. The basic heterocyclic rings present in the various medicinal agents are 1,2,3-triazole and 1,2,4-triazole. A large volume of research has been carried out on triazole and their derivatives, which has proved the pharmacological importance of this heterocyclic nucleus. The present paper is an attempt to review the pharmacological activities reported for triazole derivatives in the current literature with an update of recent research findings on this nuclei. PMID- 20583861 TI - Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes). AB - The development of serine protease inhibitors often results in the discovery of new lead compounds containing strong basic amidine functions that usually suffer from poor absorption from the intestine. In order to improve oral bioavailability of these drugs, prodrug principles such as the conversion of amidines into amidoximes may be applied. In this work, two HPLC-based separation methods of serine protease inhibitors (amidines) and their N-hydroxylated prodrugs have been developed and characterised. This was performed by evaluating 11 distinct amidine amidoxime pairs with different physicochemical parameters (clogP: -3 to 5.1). The HPLC methods developed allowed excellent separation of the compound pairs examined. Also, the possible selection of different separation techniques (i.e. adsorption- and ion-pair-chromatography) permits universal application. Moreover, both techniques are compatible with mass spectrometry and are superior to the previously described methods. In summary, both HPLC methods are suitable for the separation of most amidoxime-prodrugs currently in clinical or preclinical development. PMID- 20583862 TI - Design, synthesis and pharmacological evaluation of novel azole derivatives of aryl acetic acid as anti-inflammatory and analgesic agents. AB - A series of substituted azole derivatives (3a-e, 4a-e and 5a-e) were synthesised by the cyclisation of N(1)(diphenylethanoyl)-N(4)-substituted phenyl thiosemicarbazides under various reaction conditions. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen, were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds 5-(diphenylmethyl)-N (4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3b) and 5-(diphenylmethyl)-N-(3-chloro 4-fluorophenyl)-1,3,4-oxadiazol-2-amine (3c) emerged as the most active compounds of the series, and were moderately more potent than the standard drug, ibuprofen. (This abstract was published in Inflammation Research, Supplement 2, Volume 56, page A101, 2008.). PMID- 20583863 TI - A short polypeptide from the herpes simplex virus type 2 ICP10 gene can induce antigen aggregation and autophagosomal degradation for enhanced immune presentation. AB - It has been reported that certain polypeptides derived from aggregation-prone cellular proteins can turn soluble green fluorescent protein (GFP) into aggregates. Here we report our finding that a short peptide derived from a viral gene, ICP10 of herpes simplex virus (HSV)-2, also possesses such a property. A sequence as short as 13 amino acids from the middle region of the gene can convert GFP into an aggregation-prone toxic protein once it is fused to the C terminus. Moreover, this short peptide can direct a surrogate tumor antigen into the autophagosome/lysosome degradation pathway, drastically increasing both MHC class I and class II antigen presentation. The simultaneous induction of both arms of the T cell immune response to the tumor antigen effectively protects the immunized animals from tumor challenge. Designated VIPA (i.e., viral inducer of protein aggregation), this unique viral sequence may represent an attractive candidate as a molecular adjuvant for cancer immunotherapy and for other immunologically preventable diseases. PMID- 20583864 TI - Bis dihydropyrimidine: synthesis and antimycobacterial activity. AB - A series of bis dihydropyrimidine compounds were synthesised by reacting dapsone with acetylacetoacetate to produce N1-4-[4-(2-oxopropylcarboxamido) phenylsulphonyl] phenyl-3-oxobutanamide, then treated with guanidine hydrochloride and an appropriate aldehyde with a catalytic amount of p-toluene sulphonic acid (PTSA) in the presence of methanol to afford the title compounds. The synthesised compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv and isoniazid (INH) resistant M. tuberculosis. Among the synthesised compounds, compound N5-(4-4-[6-(4 fluorophenyl)-2-imino-4-methyl-1,2,3,4-tetrahydro-5 pyrimidinylcarboxamido]phenylsulphonylphenyl)-6-(4-fluorophenyl)-2-imino-4-methyl 1,2,3,4-tetrahydro-5-pyrimidine carboxamide (3g) was found to be the most promising compound with activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis with a minimum inhibitory concentration (MIC) between 0.08 and 0.10 MUM. PMID- 20583865 TI - Evaluating evidence and grading recommendations: the SIS/IDSA guidelines for the treatment of complicated intra-abdominal infections. AB - BACKGROUND: Guidelines for the management and treatment of complicated intra abdominal infections have been generated by a joint effort of the Surgical Infection Society and the Infectious Diseases Society of America. Continued review is needed of the process of these guideline development efforts, the evidence collected, and the recommendations developed by this collaboration. METHODS: The literature employed in the development of these guidelines and the process for the development of the recommendations was reviewed. RESULTS: The process for the development of the guidelines required providing answers to questions surrounding the type of evidence, the quality of that evidence, and whether the data used were generated from clinical trials with investigators blinded to the randomization scheme. The recommendations most commonly follow randomized comparative trials, with observational reports and expert opinions assuming a lesser role. Sources of bias and conflict of interest considerations also must be important in guideline development, with full disclosure from participants. CONCLUSIONS: Standards for the evaluation of data and recommendations in the guidelines for complicated intra-abdominal infection provided a rigorous evaluation of available clinical information. This process serves as a model for the development of additional guidelines for patient care. PMID- 20583866 TI - Avoiding colectomy during surgical management of fulminant Clostridium difficile colitis. AB - BACKGROUND: Clostridium difficile is the most common cause of nosocomial diarrhea in adults. Over the last decade, there has been a substantial increase in the disease-associated morbidity and mortality rate from this infection accompanied by identification of new hypervirulent strains. Fulminant colitis, a severe and complicated form of the disease that frequently necessitates surgical intervention, occurs in 3-8% of patients infected with C. difficile. The postoperative mortality rate for fulminant colitis continues to be dire, ranging from 34-57%. METHODS: Review of the literature to offer insight into the dilemma associated with the surgical management of fulminant C. difficile colitis and provide alternatives to total abdominal colectomy for treatment. RESULTS: Several recent studies have elucidated factors that contribute to the unacceptably high postoperative mortality rate: Surgical intervention too late in the course of the disease, lack of clearly defined guidelines for patient selection, and difficulty in predicting the clinical course of the disease. Perforation, need for vasopressor support, and end-organ damage all affect the postoperative mortality rate negatively. CONCLUSION: A high clinical suspicion and careful patient selection for colectomy is imperative to improve postoperative survival. An alternative surgical strategy for fulminant C. difficile colitis is laparoscopic creation of an ileostomy with total colonic washout. PMID- 20583867 TI - Abdominal wall infections with in situ mesh. AB - BACKGROUND: Synthetic mesh is used commonly in the repair of abdominal wall hernias. Infection at the surgical site where mesh is present poses a formidable clinical problem. METHODS: The current surgical literature was reviewed to formulate accepted approaches to the management of hernia repairs with infected mesh. RESULTS: Prevention of mesh infection is best achieved by judicious use of systemic antibiotics. Topical antibiotics often are used without convincing evidence to support their value. Laparoscopic repairs have lower infection rates than open repairs. Evidence is lacking to support lower rates of infection with mesh of specific composition or with antibacterial agents that coat the mesh. The diagnosis of mesh infection is principally a clinical one. Repairs of infected mesh usually necessitate antibiotics and removal of the foreign material. Clinical judgment is required for attempts at salvaging portions of the mesh. Component separation or biological materials may be used in those circumstances for hernia repair in which large defects are created by removal of the infected synthetic material. CONCLUSIONS: Prevention of mesh infections remains the best strategy. Clinical judgment is essential in determining the degree of mesh removal. Continued clinical studies are necessary to improve the outcomes of established mesh infection in hernia repairs. PMID- 20583868 TI - MicroRNA-20a overexpression inhibited proliferation and metastasis of pancreatic carcinoma cells. AB - The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA 20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3 mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3' untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma. PMID- 20583869 TI - Evaluating how rimantadines control the proton gating of the influenza A M2 proton port via allosteric binding outside of the M2-channel: MD simulations. AB - In order to understand how rimantadine (RMT) inhibits the proton conductance in the influenza A M2 channel via the recently proposed "allosteric mechanism", molecular dynamics simulations were applied to the M2-tetrameric protein with four RMTs bound outside the channel at the three protonation states: the 0H closed, 1H-intermediate and 3H-open situations. In the 0H-closed state, a narrow channel with the RMT-Asp44-Trp41 H-bond network was formed, therefore the water penetration through the channel was completely blocked. The Trp41-Asp44 interaction was absent in the 1H-intermediate state, whilst the binding of RMT to Asp44 remained, which resulted in a weakened helix-helix packing, therefore the channel was partially prevented. In the 3H-open state it was found that the electrostatic repulsion from the three charged His37 residues allowed the Trp41 gate to open, permitting water to penetrate through the channel. This agreed well with the potential of the means force which is in the following order: 0H > 1H > 3H. PMID- 20583870 TI - Third generation fluoroquinolones antibacterial drug based mixed-ligand Cu(II) complexes: structure, antibacterial activity, superoxide dismutase activity and DNA-interaction approach. AB - The copper(II) complexes of the type [Cu(SPF)(A(n))Cl]/[Cu(PFL)(A(n))Cl] (where SPF is sparfloxacin, PFL is pefloxacin and A(n) is 2,2'-dipyridylamine/pyridine-2 carboxalehyde/thiophene-2-carboxaldehyde) were synthesised and were found to have a pyramidal geometry with a square base. The superoxide dismutase (SOD) like activity of the complexes were measured using an NBT/NADH/PMS system, these were expressed in terms of the concentration of complex which termianates the formation of formazan by 50% (IC50 value) and found to range from 0.781 to 1.354 MUM. The interactions of the complexes with DNA were studied by absorption titration, viscosity measurement and gel electrophoresis under physiological conditions. The antimicrobial efficiency of the complexes were tested on five different microorganisms and showed good biological activity. PMID- 20583871 TI - The broad spectrum of lymphatic health and disease. PMID- 20583873 TI - Assessment of volume measurement of breast cancer-related lymphedema by three methods: circumference measurement, water displacement, and dual energy X-ray absorptiometry. AB - BACKGROUND: Following treatment for breast cancer 12%-60% develop breast cancer related lymphedema (BCRL). There are several ways of assessing BCRL. Circumference measurement (CM) and water displacement (WD) for volume measurements (VM) are frequently used methods in practice and research, respectively. The aim of this study was to evaluate CM and WD for VM of the BCRL arm and the contralateral arm, comparing the results with regional dual energy X ray absorptiometry (DXA). METHODS AND RESULTS: Twenty-four women with unilateral BCRL were included in the study. Blinded duplicate VM were obtained from both arms using the three methods mentioned above. CM and DXA were performed by two observers. WD was performed by a group of observers. Mean differences (d) in duplicated volumes, limits of agreement (LOA), and 95% confidence intervals (CI) were calculated for each method. The repeatability expressed as d (95% CI) between the duplicated VM of the BCRL arm and the contralateral arm was for DXA 3 ml (-6-11) and 3 ml (1-7), respectively. For CM and WD, the d (95% CI) of the BCRL arm were 107 ml (86-127) and 26 ml (-26-79), respectively and in the contralateral arm 100 ml (78-122) and -6 ml (-29-17), respectively. CONCLUSIONS: DXA is superior in repeatability when compared to CM and WD for VM, especially for the BCRL arm but also the contralateral arm. PMID- 20583872 TI - Lymphatic pump treatment mobilizes leukocytes from the gut associated lymphoid tissue into lymph. AB - BACKGROUND: Lymphatic pump techniques (LPT) are used clinically by osteopathic practitioners for the treatment of edema and infection; however, the mechanisms by which LPT enhances lymphatic circulation and provides protection during infection are not understood. Rhythmic compressions on the abdomen during LPT compress the abdominal area, including the gut-associated lymphoid tissues (GALT), which may facilitate the release of leukocytes from these tissues into the lymphatic circulation. This study is the first to document LPT-induced mobilization of leukocytes from the GALT into the lymphatic circulation. METHODS AND RESULTS: Catheters were inserted into either the thoracic or mesenteric lymph ducts of dogs. To determine if LPT enhanced the release of leukocytes from the mesenteric lymph nodes (MLN) into lymph, the MLN were fluorescently labeled in situ. Lymph was collected during 4 min pre-LPT, 4 min LPT, and 10 min following cessation of LPT. LPT significantly increased lymph flow and leukocytes in both mesenteric and thoracic duct lymph. LPT had no preferential effect on any specific leukocyte population, since neutrophil, monocyte, CD4+ T cell, CD8+ T cell, IgG+B cell, and IgA+B cell numbers were similarly increased. In addition, LPT significantly increased the mobilization of leukocytes from the MLN into lymph. Lymph flow and leukocyte counts fell following LPT treatment, indicating that the effects of LPT are transient. CONCLUSIONS: LPT mobilizes leukocytes from GALT, and these leukocytes are transported by the lymphatic circulation. This enhanced release of leukocytes from GALT may provide scientific rationale for the clinical use of LPT to improve immune function. PMID- 20583874 TI - Lymphatic vessel hypertrophy in inflamed human tonsils. AB - The structural and molecular properties of the human tonsil lymphatic microvascular system are important to understand as these features likely contribute to fluid balance, immunity, and tumor metastasis. The tonsil is a unique lymphoid organ in that it is in intimate contact with the contents of the upper aerodigestive tract and that there are no identifiable afferent lymphatics. Conventional immunofluorescence microscopy demonstrated a remarkable degree of lymphatic vessel architecture within the tonsil; LYVE-1-positive lymphatic vessels were detected around each germinal center and in the marginal regions between the follicles. High resolution confocal laser scanning immunofluoresence microscopy demonstrated that individual lymphatic endothelial cells had a classic 'oak leaf' shape and discontinuous expression of CD31 and VE-cadherin; characteristics hypothesized to be related to fluid and cellular transport. A comparative analysis demonstrated a dramatic increase in lymphatic but not blood vessel density and complexity in inflamed compared to noninflamed tonsil tissue. The results of this study describe the spatial organization of the tonsil lymphatic vasculature, discontinuous expression of CD31 and VE-cadherin in human lymphatic capillaries, and a change in lymphatic vessel morphology in response to inflammation. PMID- 20583875 TI - Indocyanine green and lymphatic imaging: current problems. AB - BACKGROUND: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has recently been presented as a comparatively easy and informative technique to image lymphatic channels in vivo. However, no data or references have been provided concerning the impact of ICG application on normal lymphatic contractility and lymph transport. Thus, the imaging agent and/or the method of administration may introduce a significant artifact. METHODS AND RESULTS: Standard pharmacological tests were performed to investigate the influence of ICG on the spontaneous contractility of isolated, cannulated, and pressurized rat mesenteric lymphatic vessels. The data demonstrate that non-irradiated ICG dramatically and dynamically influences the contractility of rat lymphatic vessels in both a dose- and diluent-dependent manner with low ICG concentrations principally altering contractile frequency and higher ICG concentrations completely blocking lymphatic contractility. CONCLUSIONS: Currently, both researchers and doctors should exercise caution in extrapolating the data obtained with ICG imaging to normal lymphatic function regardless of whether it was obtained in mice, pigs, or humans. Careful and extended pharmacological tests must be performed to evaluate the mechanism of action of ICG on the contractility and physiology of lymphatic vessels with consideration of dose, diluent, and duration of irradiation. PMID- 20583878 TI - Synthesis of some novel 2,5-disubstituted thiazolidinones from a long chain fatty acid as possible anti-inflammatory, analgesic and hydrogen peroxide scavenging agents. AB - Some new decanoic acid [2,5-disubstituted-4-oxo-thiazolidin-3-yl]amides (6a-j) have been synthesised by the condensation of decanoic acid hydrazide with various aromatic aldehydes to yield the Schiff's bases. Cyclocondensation of the Schiff's bases with thioglycollic acid afforded 4-thiazolidinone derivatives. The structures of the newly synthesised compounds were confirmed by analytical and spectral methods. The anti-inflammatory, analgesic and antioxidant activity of the title compounds were evaluated. Compound 6j exhibited 44.84 % inhibition of inflammation and was the most potent anti-inflammatory agent of the series whereas compound 6f demonstrated the most potent analgesic activity (69.82% inhibition of writhing) followed by compounds 6e and 6g. All the synthesised compounds exhibited a potent antioxidant activity. PMID- 20583879 TI - Intraoperative detection of gamma emissions using K-alpha X-ray fluorescence. PMID- 20583881 TI - MitraClip catheter-based mitral valve repair system. AB - The ongoing evolution of transcatheter valve technology is impressive. Mitral valve regurgitation is the most common type of heart valve insufficiency and mitral valve surgery is, next to aortic valve surgery, the second leading valvular surgical procedure in the western world. However, there is a large patient population suffering from mitral valve regurgitation that is currently not treated with heart surgery because of significant morbidity and mortality risks. This large underserved patient population could benefit from a less invasive treatment. The MitraClip system (Abbott Vascular, Menlo Park, CA, USA) is the first commercially available medical technology providing a catheter-based nonsurgical repair alternative for patients suffering from mitral valve regurgitation and has the greatest clinical experience compared with other alternative devices. The device is currently in late-stage clinical trials in the USA and has received the CE mark. PMID- 20583882 TI - Development and performance of the zotarolimus-eluting Endeavor coronary stent. AB - Given statistically significant and clinically meaningful reductions in angiographic restenosis and repeat revascularization, treatment with drug-eluting stents (DESs) has become established as a standard of care in percutaneous coronary revascularization. However, despite their superior efficacy compared with conventional bare metal stents, experiences with first-generation DESs from both clinical trials and real-world practice have raised attention to the late safety risk of stent thrombosis that may be related to biologic incompatibility, delayed vessel healing and/or impaired endothelial function. To address the outstanding needs related to DES safety and deliverability while maintaining efficacy, the Endeavor zotarolimus-eluting stent (Medtronic CardioVascular, CA, USA) is distinguished by favorable safety and efficacy demonstrated in clinical trials and usual practice. The purpose of this article is to describe the mechanical and pharmacologic features of the Endeavor stent, provide an overview of comparative trial results of the Endeavor stent with bare metal stents and alternative DESs, and detail recent and developing trials specific to the Endeavor stent that provide further insight to stent biocompatibility and safety. PMID- 20583883 TI - Heart failure: the challenge of selecting patients for implantable cardioverter defibrillator therapy. AB - Patients with heart failure die predominantly of progressive pump failure or sudden cardiac death. Therefore, it is attractive to believe that an implantable cardioverter defibrillator (ICD) will dramatically reduce mortality by reducing sudden death. However, unfortunately it is not that simple; sudden death is not the same as ICD-preventable death. While ICD prophylaxis always reduces arrhythmic death, it does not always reduce all-cause mortality due to competing risks. Importantly, an arrhythmia may be a marker for heart failure decompensation, with patients at increased risk of heart failure death following shock therapy. Randomized trials have now demonstrated the potential benefits of ICDs in selected patients with left ventricular dysfunction, yet they have also failed to demonstrate benefit in populations where one might have expected to see benefit (e.g., early post-myocardial infarction). Device therapy can offer heart failure patients much more than just a simple shock box. The addition of a left ventricular lead to allow biventricular pacing (cardiac resynchronization therapy) improves symptoms and prolongs life in selected patients with QRS prolongation. Newer technologies allow remote monitoring through the device, which offers the potential to recognize heart failure decompensation or arrhythmias early so that appropriate treatment can be instituted. However, deciding which patient should receive an ICD remains one of the most challenging questions in cardiovascular medicine. PMID- 20583884 TI - Biomimetics for the induction of bone formation. AB - The new strategy to initiate the induction of bone formation is to carve smart, self-inducing geometric cues assembled within biomimetic medical devices. These are endowed with the striking prerogative of differentiating myoblastic and/or pericytic stem cells into osteoblastic-like cells attached to the morphogenetic concavities; osteoblastic-like cells secrete osteogenic gene products of the TGF beta supergene family, further differentiating invading stem cells into osteoblastic-like cells, and initiating bone formation by induction as a secondary response. PMID- 20583885 TI - Improvement of the fatigue life of titanium alloys for biomedical devices through microstructural control. AB - A limited number of reports exist regarding the systematic investigation or comparison of the fatigue strength of titanium alloys for medical devices, including plain, fretting and notch fatigue, for improvement through various treatments and processes, with respect to related microstructures. This article focuses on the changes and improvements in fatigue strength of newly developed beta-type and practically used alpha + beta-titanium alloys for medical devices through heat treatments, thermomechanical treatments and surface modifications. PMID- 20583886 TI - Palladium alloys for biomedical devices. AB - In the biomedical field, palladium has primarily been used as a component of alloys for dental prostheses. However, recent research has shown the utility of palladium alloys for devices such as vascular stents that do not distort magnetic resonance images. Dental palladium alloys may contain minor or major percentages of palladium. As a minor constituent, palladium hardens, strengthens and increases the melting range of alloys. Alloys that contain palladium as the major component also contain copper, gallium and sometimes tin to produce strong alloys with high stiffness and relatively low corrosion rates. All current evidence suggests that palladium alloys are safe, despite fears about harmful effects of low-level corrosion products during biomedical use. Recent evidence suggests that palladium poses fewer biological risks than other elements, such as nickel or silver. Hypersensitivity to palladium alone is rare, but accompanies nickel hypersensitivity 90-100% of the time. The unstable price of palladium continues to influence the use of palladium alloys in biomedicine. PMID- 20583887 TI - Cardiac output monitoring in pediatric patients. AB - Cardiac output (CO) measurement is becoming increasingly important in the field of pediatric intensive care medicine and pediatric anesthesia. In the past few decades, various new technologies have been developed for the measurement of CO. Some of these methods are applicable to pediatric patients and some are already being used in children. The devices and methods have their advantages and limitations and, therefore, it is difficult for the clinician to decide which technique should be used. This article focuses on the currently available minimally invasive and noninvasive monitoring devices for CO measurement in children. A brief explanation of the technical aspects of each method and clinical use will be followed by the knowledge gained from infant animal and clinical pediatric studies. The goal of this article is to give an update of the various CO measurement technologies in children. PMID- 20583888 TI - Device therapy for arrhythmia management in adults with congenital heart disease. AB - The number of children with congenital heart disease surviving into adulthood has increased dramatically. Refinement in surgical techniques and effective subsequent care has mainly been responsible for this change. However, many of these survivors have significant lifestyle altering symptoms associated with rhythm disorders. These may result from the primary congenital anomaly or from surgical correction. Tachyarrhythmias often result from re-entrant circuits around surgical scars in the setting of a markedly enlarged cardiac chamber. Symptomatic bradyarrhythmias may result from surgical interruption of the conduction system or from the use of antiarrhythmic medication. The management of these lifestyle altering rhythm disorders frequently involves cardiac devices, including pacemakers, antitachycardia devices, defibrillators and resynchronization devices. We review the underlying causes for common rhythm disorders and discuss the specific challenges with cardiac device use in the adult congenital heart disease population. In addition, we address pacing for improvement of ventricular function and innovations likely to impact the field. PMID- 20583889 TI - Recent advances in the development of nucleic acid diagnostics. AB - Since the early 1970s, the use of nucleic acid sequences for specific diagnostic applications has followed a somewhat linear pattern of development. Early methods for restriction enzyme digestion, as well as reverse transcription, were followed in the late 1970s by Southern, northern and dot blotting, as well as DNA sequencing. In 1985, the description of PCR and the routine laboratory manipulation of sufficient quantities of DNA for diagnostics, resulted in the exponential growth of molecular biology. Subsequently, alternative DNA and RNA amplification protocols followed. The last 10 years have seen the second explosion in molecular biology with the development of real-time quantitative PCR and oligonucleotide microarrays. This advancement continues with the development of methods for 'direct' nucleic acid target detection from samples without in vitro amplification, and enhanced transduction elements for improved sensitivity of nucleic acid detection. In this article, we will describe the current state of the art in nucleic acid diagnostics, the use of nucleic acid-based diagnostics in clinical practice and the emerging technologies in the field. Finally, we will describe future trends and expected advances in the field. PMID- 20583890 TI - Evolution of precise and multimodal MRI and TRUS in detection and management of early prostate cancer. AB - The combination of T2-weighted MRI with functional MRI, including contrast enhanced MRI, diffusion-weighted imaging and magnetic resonance spectroscopy, has been recognized as the most promising diagnostic modality for the detection and staging of localized prostate cancer. In spite of the relatively low predictive value of the transrectal ultrasonography (US) image alone, transrectal US-guided prostate biopsy is currently the most clinically used, gold standard technique to confirm pathological prostate cancer. A possible way of improving the precision of prostate biopsy is to use computer-aided analysis, the fusion of the US image with MRI, or by introducing contrast-enhanced US, elastography and/or 3D US to be coupled with computer-assistance or robotic needle placement. Computer-aided surgical navigation systems with image-fusion or image-overlaying capability, integrated with real-time organ tracking systems and/or robotic systems for feedback on the 3D spatial positions of the surgical targets and instruments, can provide attractive opportunities to improve the digitally-coordinated precision of minimally invasive urology, along with predictive ability to guide toward ideal surgical outcomes. PMID- 20583891 TI - Cochlear implantation update: contemporary preoperative imaging and future prospects - the dual modality approach as a standard of care. AB - The selection of cochlear implant (CI) candidates requires consideration of a variety of clinical and radiographic factors. The present article reviews the current knowledge regarding the preoperative imaging of CI candidates and explores emerging developments in different imaging modalities. Preoperative radiologic assessment should evaluate the status of the middle/inner ear, auditory nerve and central acoustic pathways. Preoperative computed tomography displays anatomic middle ear variations of surgical importance. MRI can demonstrate fluid/obliteration in the inner ear and depict the retrocochlear auditory pathways. Dual modality imaging with high-resolution computed tomography and MRI of the petrous bone and brain can provide the maximum information regarding surgical landmarks and detect deafness-related abnormalities. Cost effectiveness issues also justify its use. New systems are now becoming available, offering improved soft-tissue delineation, sophisticated segmentation techniques, volumetric measurements, semitransparent views and superior surface resolution, thus significantly advancing our diagnostic acumen and making the preoperative evaluation of CI candidates more accurate and reliable. PMID- 20583894 TI - The effect of acute administration of rifampicin and imatinib on the enterohepatic transport of rosuvastatin in vivo. AB - Hepatobiliary transporters efficiently shunt rosuvastatin from the blood stream, into the hepatocyte, followed by transporter-mediated excretion into the bile ducts. This study aimed at investigating the contribution of sinusoidal versus canalicular transport on the pharmacokinetics of an intrajejunal dose of 80 mg rosuvastatin in pigs (control group, n = 2 + 6). The transport inhibitors, rifampicin (20 mg/kg, n = 6) and imatinib (14 mg/kg, n = 6), were administered as 2-h long intravenous infusions. Plasma samples were withdrawn from the portal and hepatic vein simultaneously during 5 h along with bile sample collection. Rifampicin reduced the hepatic extraction of rosuvastatin by 35% and the area under the curve in the hepatic vein compartment increased by a factor of 6.3 (95% confidence intervals (CI): 3.1-32, P value <0.01). The increase in the portal vein compartment was less pronounced than in the hepatic vein, 2.0-fold (95% CI: 1.1-3.8, P value <0.05), suggesting that the inhibition was predominantly located in the liver rather than in the intestine and suggesting inhibition if sinusoidal transport. In contrast, no effect on the pharmacokinetics of rosuvastatin was observed following concomitant administration with imatinib possibly due to insufficient concentration of the inhibitor inside the hepatocyte. Rifampicin significantly affected the hepatobiliary transport of rosuvastatin, however imatinib did not alter the plasma exposure of rosuvastatin. PMID- 20583895 TI - Malondialdehyde and superoxide dismutase correlate with FEV(1) in patients with COPD associated with wood smoke exposure and tobacco smoking. AB - Tobacco smoking is the primary risk factor for chronic obstructive pulmonary disease (COPD). However, recent epidemiological studies have established domestic exposure to wood smoke and other biomass fuels as additional important risk factors, characteristic in developing countries. Oxidative stress is one of the mechanisms concerned with pathogenesis of COPD. However, the molecular mechanisms involved in the onset and progress of COPD associated with biomass and specifically that derived from wood smoke exposure remain unknown. We analyzed the relationship between forced expiratory volume in first second (FEV(1)) with plasma malondialdehyde (MDA) concentration and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in COPD patients associated with wood smoke (WSG; n = 30), tobacco smoking (TSG; n = 30), and healthy control subjects (HCG; n = 30). Differences between FEV(1) from WSG and TSG (58 +/- 22% and 51 +/- 24%, respectively) with HCG (100 +/- 6%) were observed (P < 0.01). Plasma MDA concentration was higher in both WSG and TSG (1.87 +/- 0.81 and 1.68 +/- 0.82 nmol/mL, respectively) compared with HCG (0.42 +/- 0.17 nmol/mL; P < 0.01). SOD activity showed a significant increase in both WSG and TSG (0.36 +/- 0.12 and 0.37 +/- 0.13 U/mL) compared with HCG (0.19 +/- 0.04 U/mL; P < 0.01). No differences were shown regarding GPx, GR, and GST activities between COPD and control groups. Inverse correlations were founded between MDA and SOD with FEV(1) in both COPD patients and control subjects (P < 0.001). These results indicate a role for oxidative stress in COPD associated with wood smoke similar to that observed with tobacco smoking in subjects who ceased at least 10 years previous to this study. PMID- 20583896 TI - Multifocal chorangiomatosis. AB - Multifocal chorangiomatosis (MC) is an uncommon villous capillary lesion sharing some features with villous chorangiosis and placental chorangioma. We prospectively identified 53 cases of MC among 5429 consecutively accessioned placentas of >20 weeks gestation over a 10-year period. Two gestational age (GA) matched controls were selected for each case from the same cohort and a case control analysis of associated clinical and pathologic features was performed. Multifocal chorangiomatosis was seen at all GAs but was most frequent in very preterm placentas (<32 weeks). Avascular villi, villous chorangiosis, and distal villous immaturity were each seen in approximately half of placentas with MC. Other common placental findings included concentric narrowing of fetal villous arterioles, villous edema, and dysmorphic villi. Only one case had an associated placental chorangioma. Maternal factors significantly associated with MC were advanced maternal age, non-African-American ancestry, nonprimigravid status, and >5 previous pregnancies. Infants with placental MC had a significantly increased prevalence of congenital anomalies. Multifocal chorangiomatosis was subcategorized as extensive versus patchy based on the size of the largest focus (> versus < *2 microscopic field). Fetuses with extensive MC, when compared with patchy MC, were more likely to have congenital anomalies and stillbirth and to be large for GA. Paradoxically, those with patchy MC were more likely to be small for GA. The results of this study suggest that MC may represent an abnormal proliferation of the paravascular capillary net in proximal villi related to fetoplacental developmental anomalies and abnormal fetal blood flow. PMID- 20583897 TI - Different sensitivity in expression of transcription factor mRNAs in congenic mice following exposure to low-level toluene. AB - To investigate the relationship between sensitivity to toluene exposure and genetic background, male congenic mice, C57BL/10 (H-2(b)) and B10.BR/Sg (H-2(k)) were exposed to 0, 5, and 50 ppm toluene for 6 h per day, 5 days per week for 6 weeks. Groups of mice were injected with ovalbumin (OVA) intraperitoneally before starting exposure schedule and these mice were then challenged with aerosolized OVA as a booster. Following 24 h of the last exposure, the spleens were collected. We examined spleen cell proliferation using DNA synthesis and T-helper 1/2-related transcription factor genes in spleen of two congenic mice using real time reverse transcriptase-polymerase chain reaction. Although lipopolysaccharide induced (LPS-induced) cell proliferation was significantly increased in 50 ppm toluene-exposed, nonimmunized B10.BR mice but not in C57BL/10 mice, exposure to 50 ppm toluene significantly decreased LPS-induced cell proliferation in immunized B10.BR mice. The expression of transcription factor forkhead box P3, signal transducers and activators of transcription (STAT)5 and STAT6 mRNAs was significantly increased in spleen from 5 ppm toluene-exposed, OVA-immunized B10.BR mice, but not in those of C57BL/10 mice. Although there may be other differences unrelated to H-2 locus between the congenic mice of the same background, the findings of the present study strongly suggest a possible role of H-2 locus in the toluene-induced immune disturbance. PMID- 20583898 TI - Classical neurotransmitters and neuropeptides involved in major depression: a review. AB - We propose several pathways that could be involved in major depression. According to our proposal, noradrenaline hypoactivity could occur through a strong presynaptic GABAergic inhibition, via GABA(B) receptors, and serotonin hypoactivity through a strong glutaminergic inhibition via subreceptor 5 of the metabotropic glutaminergic receptor. In this sense, it is important to know whether the antagonists of such receptors might be able to improve the symptoms observed in major depression. Some neuropeptides are also altered in such states (corticotropin-releasing hormone, neuropeptide Y, galanin). It is also important to know whether in addition to current antidepressants the administration of neuropeptides and their agonists/antagonists could ameliorate depressive symptoms. PMID- 20583899 TI - More than meets the eye? Redefining idiopathic intracranial hypertension. AB - Idiopathic intracranial hypertension (IIH) is a disease of unknown etiology associated with increased intracranial pressure, predominantly affecting obese females of childbearing age. The history of IIH is quite unique, featuring only limited advancements in evidenced-based treatments, but boasting literally countless changes in nomenclature, proposed etiology, and conceptual approach. Despite its elusive pathogenesis, an evolution of our approach to IIH can be traced sequentially through identifiable periods. Contemporary research suggests that we are approaching a new phase in IIH, redefining it as a global neurologic syndrome with more far-reaching effects than previously realized. PMID- 20583900 TI - Human prefrontal cortical response to the meditative state: a spectroscopy study. AB - The effect of Qigong meditation on the hemodynamics of the prefrontal cortex was investigated by spectroscopy with a single-wavelength probe (650 nm) and confirmed by standard near-infrared spectroscopy with a dual-wavelength probe. Deoxyhemoglobin changes were recorded with the single-wavelength probe over the left prefrontal cortex during meditation by Qigong practitioners, and non practitioners instructed in the technique. Practitioners showed a significant decrease in deoxyhemoglobin levels suggesting an increase in prefrontal activation during meditation. The results were confirmed in a second set of experiments with the standard dual-wavelength probe, in which significant differences in the decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations were observed in practitioners as compared with non-practitioners. The study thus provides evidence that Qigong meditation has a significant effect on prefrontal activation. PMID- 20583901 TI - Estrogen reduces BDNF level, but maintains dopaminergic cell density in the striatum of MPTP mouse model. AB - Degeneration of dopaminergic (DA) axons in the striatum triggers upregulation of striatal trophic activity and striatal DA neuronal number in animal models of Parkinson's disease (PD). The present study investigated the effects of 17beta estradiol (E2) on brain-derived neurotrophic factor (BDNF) expression and the density of DA neurons in the striatum of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) mouse model in correlation with nigrostriatal DA innervation. Adult male C57Bl/6 mice were treated with E2 or vehicle for 11 days. Following 5 days of E2 or vehicle pretreatment, animals were injected with MPTP on day 6. On day 11, all mice were sacrificed, and the striatum were collected and processed for tyrosine hydroxylase (TH) and BDNF immunohistochemistry. Striatal TH-immunoreactive (IR) neurons were counted. Extent of DA innervation and BDNF expression in the striatum were assessed by measuring optical density of TH and BDNF immunoreactivity, respectively. Pretreatment with E2 partially prevented DA denervation and decreased striatal BDNF upregulation triggered by MPTP, but maintained the density of striatal TH-IR neurons to that observed in MPTP group. These findings suggest that estrogen protection of nigrostriatal DA axons against MPTP as well as preservation of the striatal TH-IR cell density in MPTP/E2 mice may be not mediated by BDNF. PMID- 20583902 TI - Polymorphisms of the prion protein gene (PRNP) in a Serbian population. AB - Prion diseases are a group of etiologically heterogeneous neurodegenerative disorders. We have analyzed the coding region of PRNP gene in 121 healthy citizens of Serbia to determine whether the frequencies of M129V, E219K, and octapeptide repeat number polymorphism. For Serbian population, polymorphism of PRNP gene at codon 129 does not differ from healthy European populations. Also codon 219 is monomorphic for the Glu allele both in Serbian population and other European populations. On the contrary, in Serbian population we did not detect any deletions or insertions in octapeptide repeat region, whereas deletions were detected in other European populations. PMID- 20583903 TI - Schizophrenia and apolipoprotein E gene polymorphism in Serbian population. AB - Apolipoprotein E (APOE) gene variants are associated with alterations in brain function and increased risk of Alzheimer's disease (AD) and conflicting results have been reported in schizophrenia. Our results showed no significant differences in APOE allele or genotype frequencies between the Serbian schizophrenic patients and control individuals. However, we observed a possible association between particular subtypes of schizophrenia and APOE epsilon3/epsilon3 genotype (p = .01221) and epsilon4 allele showed a tendency toward positive association with responding to typical neuroleptics. APOE genotypes have no major influence on risk of schizophrenia, treatment and response to conventional antipsychotics, and age of onset in schizophrenia. PMID- 20583904 TI - The relationship between akathisia and subjective tolerability in patients with schizophrenia. AB - Akathisia remains a significant issue even in the era of atypical antipsychotics. The purpose of the present study was to examine the association of akathisia with various domains of subjective tolerability in order to contribute to the renewed interest in akathisia and the subjective experience of antipsychotic treatment. Fifty schizophrenic outpatients receiving stable doses of risperidone were evaluated for akathisia, schizophrenic symptoms, and subjective tolerability. Subjective tolerability was comprehensively assessed using the Liverpool University Neuroleptic Side Effect Rating Scale. Analysis of covariance revealed that the akathisia group had a significantly higher total score as well as higher subscale scores of extrapyramidal side effect, psychic side effect, and autonomic side effect on the Liverpool University Neuroleptic Side Effect Rating Scale. Further analysis using binary logistic regression analysis revealed that these variables were significantly associated with akathisia. The results of our study suggest that akathisia is significantly associated with a wide range of subjective tolerability profiles, implying the necessity to effectively manage akathisia even its mild forms considering its strong association with subjective tolerability in general. PMID- 20583905 TI - Disinhibition in the unaffected hemisphere is related with the cortical involvement of the affected hemisphere. AB - To investigate whether the disinhibition of the unaffected hemisphere (UH) is related with the lesion location or integrity of the corticospinal tract, we evaluated the intracortical excitability of hand motor cortex in the UH using a paired-pulse transcranial magnetic stimulation paradigm short intracortical inhibition (sICI) and intracortical facilitation (ICF) in 30 subacute stroke survivors. The participants were then classified according to the lesion locations (cortical versus subcortical) and the presence of motor-evoked potential (MEP) response on the paretic hand (MEP+ versus MEP-). The sICI and ICF in the UH were compared according to lesion location and presence of paretic MEP. The sICI and ICF in the UH were comparable between MEP+ and MEP- groups. However, in terms of lesion location, intracortical inhibition was present in patients with subcortical lesions, whereas the patients with cortical lesions showed significant disinhibition in the UH. In conclusion, these findings support that the disinhibition of UH in subacute stage is related to the location of lesion rather than the integrity of the corticospinal tract. PMID- 20583908 TI - Representation invariant genetic operators. AB - A genetic algorithm is invariant with respect to a set of representations if it runs the same no matter which of the representations is used. We formalize this concept mathematically, showing that the representations generate a group that acts upon the search space. Invariant genetic operators are those that commute with this group action. We then consider the problem of characterizing crossover and mutation operators that have such invariance properties. In the case where the corresponding group action acts transitively on the search space, we provide a complete characterization, including high-level representation-independent algorithms implementing these operators. PMID- 20583906 TI - Paradoxical embolus across atrial septal defect and posterior circulation infarct in neurosurgical patients. AB - Paradoxical embolism through a patent foramen ovale or atrial septal defect is increasingly recognized in association with embolic strokes, with the advent of modern echocardiography. The authors describe two neurosurgical cases with such an anomaly that suffered nonfatal embolic stroke in the cerebellum. The patients developed posterior inferior cerebellar artery infarcts, which were managed conservatively and had no neurological deficits. They evaluate possible factors for emboli to occur in a perioperative neurosurgical setting and provide a brief review of literature on preoperative management of patients with this cardiac defect. Closure of cardiac shunts is warranted before non-emergent neurosurgical operations. During emergency craniotomies, proper precautions should be taken to reduce the incidence of venous air embolism and paradoxical embolism. PMID- 20583909 TI - Computer-automated evolution of an X-band antenna for NASA's Space Technology 5 mission. AB - Whereas the current practice of designing antennas by hand is severely limited because it is both time and labor intensive and requires a significant amount of domain knowledge, evolutionary algorithms can be used to search the design space and automatically find novel antenna designs that are more effective than would otherwise be developed. Here we present our work in using evolutionary algorithms to automatically design an X-band antenna for NASA's Space Technology 5 (ST5) spacecraft. Two evolutionary algorithms were used: the first uses a vector of real-valued parameters and the second uses a tree-structured generative representation for constructing the antenna. The highest-performance antennas from both algorithms were fabricated and tested and both outperformed a hand designed antenna produced by the antenna contractor for the mission. Subsequent changes to the spacecraft orbit resulted in a change in requirements for the spacecraft antenna. By adjusting our fitness function we were able to rapidly evolve a new set of antennas for this mission in less than a month. One of these new antenna designs was built, tested, and approved for deployment on the three ST5 spacecraft, which were successfully launched into space on March 22, 2006. This evolved antenna design is the first computer-evolved antenna to be deployed for any application and is the first computer-evolved hardware in space. PMID- 20583910 TI - Theoretical convergence guarantees for cooperative coevolutionary algorithms. AB - Cooperative coevolutionary algorithms have the potential to significantly speed up the search process by dividing the space into parts that can each be conquered separately. However, recent research presented theoretical and empirical arguments that these algorithms tend to converge to suboptimal solutions in the search space, and are thus not fit for optimization tasks. This paper details an extended formal model for cooperative coevolutionary algorithms, and uses it to explore possible reasons these algorithms converge to optimal or suboptimal solutions. We demonstrate that, under specific conditions, this theoretical model will converge to the globally optimal solution. The proofs provide the underlying theoretical foundation for a better application of cooperative coevolutionary algorithms. We demonstrate the practical advantages of applying ideas from this theoretical work to a simple problem domain. PMID- 20583911 TI - Evolutionary dynamics of tag mediated cooperation with multilevel selection. AB - Understanding the conditions and dynamics that produce cooperation in evolving systems remains a fundamental goal of evolutionary theory. Significant progress has been made in determining the conditions that support cooperation in simple models, but the evolutionary dynamics that lead from noncooperative conditions to cooperation are still poorly understood. And, in more complex models, even the conditions that support cooperation are not well defined. In this paper we study the dynamics of the evolution of cooperation in both a simple tag-mediated cooperation model and in a more complex version of the same system in which there is multilevel competition--competition between both individuals and populations of individuals. The results show that the inclusion of multilevel competition has both quantitative effects (increasing the frequency and duration of the periods of cooperation) and qualitative effects (introducing a new stable state) on the evolutionary dynamics of cooperation. PMID- 20583912 TI - Approximating covering problems by randomized search heuristics using multi objective models. AB - The main aim of randomized search heuristics is to produce good approximations of optimal solutions within a small amount of time. In contrast to numerous experimental results, there are only a few theoretical explorations on this subject. We consider the approximation ability of randomized search heuristics for the class of covering problems and compare single-objective and multi objective models for such problems. For the VertexCover problem, we point out situations where the multi-objective model leads to a fast construction of optimal solutions while in the single-objective case, no good approximation can be achieved within the expected polynomial time. Examining the more general SetCover problem, we show that optimal solutions can be approximated within a logarithmic factor of the size of the ground set, using the multi-objective approach, while the approximation quality obtainable by the single-objective approach in expected polynomial time may be arbitrarily bad. PMID- 20583913 TI - Learning factorizations in estimation of distribution algorithms using affinity propagation. AB - Estimation of distribution algorithms (EDAs) that use marginal product model factorizations have been widely applied to a broad range of mainly binary optimization problems. In this paper, we introduce the affinity propagation EDA (AffEDA) which learns a marginal product model by clustering a matrix of mutual information learned from the data using a very efficient message-passing algorithm known as affinity propagation. The introduced algorithm is tested on a set of binary and nonbinary decomposable functions and using a hard combinatorial class of problem known as the HP protein model. The results show that the algorithm is a very efficient alternative to other EDAs that use marginal product model factorizations such as the extended compact genetic algorithm (ECGA) and improves the quality of the results achieved by ECGA when the cardinality of the variables is increased. PMID- 20583914 TI - Red-light light-emitting diode irradiation increases the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells. AB - OBJECTIVE: The objective of this study was to investigate the effects on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (MSCs) by using red-light light-emitting diode (LED) irradiation. BACKGROUND DATA: Low level light irradiation (LLLI) has been shown to enhance proliferation and cytokine secretion of a number of cells. MSCs are capable of regenerating various mesenchymal tissues and are essential in supporting the growth and differentiation of hematopoietic stem cells within the bone marrow. MATERIALS AND METHODS: Rat bone marrow MSCs were treated with single or multiple doses of LLLI from an LED array (630 nm) at the irradiances of 5 and 15 mW/cm(2), and radiant exposures of 2 and 4 J/cm(2). The proliferation, clonogenic potential, and osteogenic differentiation of MSCs were evaluated after illumination. RESULTS: The growth of MSCs was enhanced by red-light LLLI, and the effect became more obvious at low cell density. A single dose of LLLI led only to a short-term increase in MSCs proliferation. A maximal increase in cell proliferation was observed with multiple exposures of LLLI at 15 mW/cm(2) and 4 J/cm(2). The number of colony-forming unit fibroblasts increased when cells were illuminated under the optimal parameter. During osteogenesis, significant increases (p < 0.01) in both alkaline phosphatase and osteocalcin expressions were found in the MSCs that received light irradiation. CONCLUSION: Our data demonstrated that MSCs proliferation was enhanced by multiple exposures to LLLI from 630-nm LEDs, and cell growth depended on the plating density. Furthermore, multiple dose of LLLI could enhance the osteogenic potential of rat MSCs. PMID- 20583915 TI - Autogenous periosteal barrier membranes and bone grafts in the treatment of periodontal intrabony defects of single-rooted teeth: a 12-month reentry randomized controlled clinical trial. AB - BACKGROUND: This randomized clinical trial compares the outcomes of combination treatment by autogenous periosteal membranes and bone graft versus guided tissue regeneration (GTR) with collagen membranes or open-flap debridement (OFD) only in the treatment of intraosseous defects. METHODS: Forty-two patients affected by moderate to severe chronic periodontitis were enrolled. Each patient had one deep intrabony defect (>=6 mm). They were randomly assigned into three groups: patients treated with 1) an OFD procedure alone (OFD group); 2) a GTR procedure with collagen membranes (GTR group); and 3) a combined treatment procedure by autogenous periosteal membranes and autogenous bone chips (aCPRT group). Clinical and intrasurgical examinations including probing depth (PD), clinical attachment level (CAL), gingival recession (GR), and defect bone level (DBL) were performed at baseline and after 1 year. RESULTS: After 1 year, all of the evaluated clinical parameters showed statistically significant changes from baseline within each group (P <0.01). The GTR and aCPRT groups had significantly greater PD reductions (5.2 and 4.4 mm, respectively) and CAL (3.2 and 3.9 mm) and DBL gains (2.4 and 3.1 mm) compared to the OFD group (PD, 2.9 mm; CAL, 1.6 mm; DBL, 1.5 mm); moreover, the aCPRT group showed a significantly smaller GR increase (0.5 mm) and a greater DBL gain (3.1 mm) compared to the GTR group (2 and 2.4 mm, respectively; P <0.05). CONCLUSIONS: Both the GTR and aCPRT treatments produce additional clinical benefits over OFD alone. Moreover, the aCPRT technique can minimize post-surgical GR and produce better defect bone-level improvement. PMID- 20583916 TI - Increased prevalence of cardiovascular and autoimmune diseases in periodontitis patients: a cross-sectional study. AB - BACKGROUND: Associations between periodontitis and cardiovascular and autoimmune diseases are most often assessed in patients with a particular cardiovascular or autoimmune disease. To prevent selection bias, this study assesses the existence of associations between periodontitis and cardiovascular and autoimmune diseases in patients attending a dental or periodontal clinic. METHODS: Data were collected from 1,276 randomly selected dental records from patients attending a dental (n = 588) or periodontal (n = 688) clinic. Data on the prevalence of cardiovascular and autoimmune diseases were obtained from a validated health questionnaire. Data on the presence of periodontitis were taken from patients' dental records. RESULTS: In uncontrolled analyses, the prevalence of hypertension, diabetes mellitus (DM), and rheumatoid arthritis (RA) is significantly increased in patients with periodontitis. Controlled for confounding, periodontitis was associated with DM, with an odds ratio of 4 (1.03 to 15.3), in the dental clinic. DM was not associated with periodontitis in periodontal clinics. Hypertension does not seem to be associated with periodontitis when controlling for confounders. Periodontitis may be associated with RA in both clinic types. CONCLUSIONS: The increased prevalence of cardiovascular and autoimmune diseases among patients with periodontitis attending dental or periodontal clinics may, at least in part, be influenced by confounding. However, the increased prevalence of DM and RA in patients with periodontitis could not be explained by confounding. PMID- 20583917 TI - Oral malodorous compound induces osteoclast differentiation without receptor activator of nuclear factor kappaB ligand. AB - BACKGROUND: Hydrogen sulfide (H(2)S), the main component of halitosis, is one of the etiologic factors for periodontitis. We recently reported that H(2)S may induce pathologic changes in rat alveolar bone. The objective of this study is to determine the effect of H(2)S on osteoclast differentiation. METHODS: Murine macrophage cells RAW264 were cultured in medium lacking nuclear factor kappaB ligand (receptor activator of nuclear factor kappaB ligand) in 5% CO(2) with air at 37 degrees C for 24 hours; then 0.05, 0.5, or 5 ng/ml H(2)S was added to the CO(2)-air mix for 4 days. The controls received the CO(2)-air mix with no H(2)S. Cell differentiation was evaluated by counting the tartrate-resistant acid phosphatase (TRAP)-positive cells. Extracellular signaling-regulated kinase1/2 (ERK1/2) and mitogen-activated protein kinase p38 phosphorylation were examined by Western blotting. The bone-resorption activity was determined with the resorption assay of calcium phosphate. RESULTS: There were significantly more TRAP-positive cells at a concentration of 0.05 ng/ml H(2)S than at the other concentrations (P <0.001). Cathepsin K protein, a specific marker for osteoclasts, was expressed in the H(2)S-induced multinuclear cells. Resorption of calcium phosphate significantly increased in the H(2)S-induced TRAP-positive cells cultured on plates coated with calcium phosphate apatite (P <0.01). The phosphorylation of ERK1/2 and p38 were accelerated by H(2)S, and increased with time. PD98059 and SB203580, specific inhibitors of ERK1/2 and p38, suppressed the activation of these enzymes and osteoclast differentiation by H(2)S. CONCLUSION: Results demonstrate that H(2)S at physiologic concentrations in mouth air induces osteoclasts from RAW264 cells. PMID- 20583918 TI - A systematic review of clinical efficacy of adjunctive antibiotics in the treatment of smokers with periodontitis. AB - BACKGROUND: The aim of this study is to systematically review the evidence of the efficacy of adjunctive antibiotic therapy to periodontal therapy in smokers with periodontitis. METHODS: A search was conducted for randomized clinical trials (RCTs) with durations >=6 months that compared periodontal therapy with and without adjunctive antibiotics for the treatment of periodontitis in smokers. Data sources primarily included PubMed with MeSH terms and free text as well as EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Clinical Trials. In addition, a hand search of selected periodontal journals, bibliographies, and review articles was conducted. Independent reviewers were assigned to make independent searches and quality assessments (MA and DB) of the included studies, and disagreements were resolved by discussion. RESULTS: Five RCTs were selected for quantitative and qualitative assessments. Little evidence was found that supported the use of antibiotic therapy in conjunction with surgical periodontal therapy in smokers. With respect to non-surgical therapy, consistent improvements in clinical attachment level (CAL) gain and probing depth (PD) reduction was reported after the use of a 250-mg azithromycin tablet in one study. Adjunctive doxycycline gel and minocycline microspheres statistically improved CAL gain (in one RCT) and PD reduction (in one RCT), respectively. However, the risk of bias in all studies was estimated as high. Also, inadequate and inconsistent data precluded performing meta-analyses. CONCLUSIONS: The present systematic review concludes that the evidence for an additional benefit of adjunctive antibiotic therapy in smokers with chronic periodontitis is insufficient and inconclusive. Additional well-designed RCTs are required to assess the effect of antibiotics in conjunction with periodontal treatments in smokers. PMID- 20583919 TI - Comparison between micro- and macrosurgical techniques for the treatment of localized gingival recessions using coronally positioned flaps and enamel matrix derivative. AB - BACKGROUND: The aim of this study is to compare the macro- and microsurgery techniques for root coverage using a coronally positioned flap (CPF) associated with enamel matrix derivative (EMD). METHODS: Thirty patients were selected for the treatment of localized gingival recessions (GRs) using CPF associated to EMD. Fifteen patients were randomly assigned to the test group (TG), and 15 patients were randomly assigned to the control group (CG). The microsurgical approach was performed in the TG, and the conventional macrosurgical technique was performed in the CG. The clinical parameters evaluated before surgery and after 6 months were GR, probing depth, relative clinical attachment level, width of keratinized tissue (WKT), and thickness of keratinized tissue (TKT). The discomfort evaluation was performed 1 week postoperative. RESULTS: There were no statistically significant differences between groups for all parameters at baseline. At 6 months, there was no statistically significant difference between the techniques in achieving root coverage. The percentage of root coverage was 92% and 83% for TG and CG, respectively. After 6 months, there was a statistically significant increase of WKT and TKT in TG only. Both procedures were well tolerated by all patients. CONCLUSIONS: The macro- and microsurgery techniques provided a statistically significant reduction in GR height. After 6 months, there was no statistically significant difference between the techniques regarding root coverage, and the microsurgical technique demonstrated a statistically significant increase in WKT and TKT. PMID- 20583920 TI - Effect of HIV infection status and anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants. AB - Serotype-specific antibody concentration and opsonophagocytic activity (OPA) were evaluated after 3 doses of pneumococcal conjugate vaccine. Groups included human immunodeficiency virus (HIV)-positive infants with CD4(+) cell percentages > or =25% who initiated immediate antiretroviral treatment (the HIV+/ART+ group) or whose antiretroviral treatment was deferred until clinically or immunologically indicated (the HIV+/ART- group). Immune responses were also evaluated in HIV noninfected infants born to HIV-seronegative (M-/I-) or HIV-positive mothers (M+/I-). Antibody concentrations were similar between HIV+/ART+ and HIV+/ART- infants. However, antibody concentrations were lower in M-/I- infants than in M+/I- infants. Nevertheless, M-/I- infants had superior OPA responses, compared with those in HIV+/ART+ infants, who in turn had better OPA responses, compared with those in HIV+/ART- infants. PMID- 20583922 TI - Impact of results of methicillin-resistant Staphylococcus aureus surveillance culture of nasal specimens on subsequent antibiotic prescribing patterns. AB - We studied the potential impact of results of methicillin-resistant Staphylococcus aureus (MRSA) surveillance culture of nasal specimens on physicians' vancomycin-prescribing habits. We compared 116 case patients who had positive results with 116 matched control subjects who had negative results. On multivariate analyses, a positive MRSA carrier status remained strongly predictive of vancomycin use within the subsequent 12 weeks. PMID- 20583921 TI - T-bet, GATA-3, and Foxp3 expression and Th1/Th2 cytokine production in the clinical outcome of human infection with Leishmania (Viannia) species. AB - BACKGROUND: T cell differentiation determines susceptibility and resistance to experimental cutaneous leishmaniasis, yet mixed T1/Th2 responses characterize the clinical spectrum of human infection with Leishmania (Viannia) species. MATERIALS AND METHODS: To discern the interrelationship of T cell differentiation and outcome of human infection, we examined factors that regulate T cell differentiation and Th1/Th2 cytokine responses in asymptomatic infection, active and historical chronic and recurrent cutaneous leishmaniasis. T-bet, GATA-3, Foxp3, and cytokine gene expression were quantified by real-time polymerase chain reaction and correlated with interleukin 2, interferon gamma, tumor necrosis factor alpha, interleukin 4, interleukin 13, and interleukin 10 secretion during in vitro response to live Leishmania panamensis. RESULTS: Higher GATA-3 expression than T-bet expression occurred throughout the 15 days of coculture with promastigotes; however, neither transcription nor secretion of interleukin 4 was detected. A sustained inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines interferon gamma and tumor necrosis factor alpha was observed in asymptomatic infection. In contrast, higher T-bet expression and a higher ratio of T-bet to GATA-3 characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased interleukin 2 secretion, compared with control subjects, was directly correlated with Foxp3 expression and interleukin 13 secretion in chronic disease. CONCLUSIONS: Regulation of the inflammatory response rather than biased Th1/Th2 response distinguished asymptomatic and recalcitrant outcomes of infection with Leishmnania viannia species. PMID- 20583923 TI - Comparison of costs of surgical site infection and endometritis after cesarean delivery using claims and medical record data. AB - We used administrative and clinical data from a case-control study to calculate the costs of surgical site infection and endometritis after cesarean delivery. Attributable costs determined by multivariate generalized least-squares regression models with the 2 data sets were similar, suggesting that administrative data can be used to calculate infection costs. PMID- 20583925 TI - The imperfect ancestral recombination graph reconstruction problem: upper bounds for recombination and homoplasy. AB - One of the central problems in computational biology is the reconstruction of evolutionary histories. While models incorporating recombination and homoplasy have been studied separately, a missing component in the theory is a robust and flexible unifying model which incorporates both of these major biological events shaping genetic diversity. In this article, we introduce the first such unifying model and develop algorithms to find the optimal ancestral recombination graph incorporating recombinations and homoplasy events. The power of our framework is the connection between our formulation and the Directed Steiner Arborescence Problem in combinatorial optimization. We implement linear programming techniques as well as heuristics for the Directed Steiner Arborescence Problem, and use our methods to construct evolutionary histories for both simulated and real data sets. PMID- 20583924 TI - An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. AB - BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma (KS) and multicentric Castleman disease (MCD) in human immunodeficiency virus (HIV)-infected patients. Patients with KSHV-MCD develop fevers, wasting, hypoalbuminemia, cytopenias, and hyponatremia that are related to overproduction of KSHV-encoded viral interleukin (IL)-6 (vIL-6) and human IL-6 (hIL-6). METHODS: We identified 6 HIV-infected patients with KS or serological evidence of KSHV infection who had severe inflammatory MCD-like symptoms but in whom we could not diagnose MCD, and we hypothesized that these symptoms resulted from vIL-6 overproduction. Serum vIL-6 levels were assessed in these 6 patients and compared with levels in 8 control patients with symptomatic KSHV-MCD and 32 control patients with KS. KSHV viral load, serum hIL-6 level, and human IL-10 level were also evaluated. RESULTS: Patients with inflammatory MCD-like symptoms but without MCD had elevated vIL-6 levels, comparable with levels in patients with symptomatic KSHV-MCD, and had levels that were significantly greater than those in control patients with KS (P = .003). Elevated hIL-6, IL-10, and KSHV viral loads were also comparable to patients with symptomatic KSHV-MCD and significantly greater than those with KS. CONCLUSIONS: A subset of patients with HIV and KSHV co-infection, but without MCD, can develop severe systemic inflammatory symptoms associated with elevated levels of KSHV vIL-6, IL-6, and KSHV viral loads. Excess lytic activation of KSHV, production of the lytic gene product vIL6, and associated immunologic dysregulation may underlie the pathophysiology of these symptoms. This IL-6-related inflammatory syndrome is important to consider in critically ill patients with HIV and KSHV co-infection. PMID- 20583926 TI - A probabilistic and continuous model of protein conformational space for template free modeling. AB - One of the major challenges with protein template-free modeling is an efficient sampling algorithm that can explore a huge conformation space quickly. The popular fragment assembly method constructs a conformation by stringing together short fragments extracted from the Protein Data Base (PDB). The discrete nature of this method may limit generated conformations to a subspace in which the native fold does not belong. Another worry is that a protein with really new fold may contain some fragments not in the PDB. This article presents a probabilistic model of protein conformational space to overcome the above two limitations. This probabilistic model employs directional statistics to model the distribution of backbone angles and 2(nd)-order Conditional Random Fields (CRFs) to describe sequence-angle relationship. Using this probabilistic model, we can sample protein conformations in a continuous space, as opposed to the widely used fragment assembly and lattice model methods that work in a discrete space. We show that when coupled with a simple energy function, this probabilistic method compares favorably with the fragment assembly method in the blind CASP8 evaluation, especially on alpha or small beta proteins. To our knowledge, this is the first probabilistic method that can search conformations in a continuous space and achieves favorable performance. Our method also generated three dimensional (3D) models better than template-based methods for a couple of CASP8 hard targets. The method described in this article can also be applied to protein loop modeling, model refinement, and even RNA tertiary structure prediction. PMID- 20583927 TI - Code optimization of the subroutine to remove near identical matches in the sequence database homology search tool PSI-BLAST. AB - A central task in protein sequence characterization is the use of a sequence database homology search tool to find similar protein sequences in other individuals or species. PSI-BLAST is a widely used module of the BLAST package that calculates a position-specific score matrix from the best matching sequences and performs iterated searches using a method to avoid many similar sequences for the score. For some queries and parameter settings, PSI-BLAST may find many similar high-scoring matches, and therefore up to 80% of the total run time may be spent in this procedure. In this article, we present code optimizations that improve the cache utilization and the overall performance of this procedure. Measurements show that, for queries where the number of similar matches is high, the optimized PSI-BLAST program may be as much as 2.9 times faster than the original program. PMID- 20583928 TI - The integration of genetic maps using Bayesian inference. AB - In the absence of a comprehensive sequence-based map of a species' genome, genetic maps constitute the next best source of genetic information. Information derived from such maps can be used, for example, in identifying the genes that form quantitative trait loci (QTLs) and for performing comparative genomics between species. Integrating information from a collection of maps will provide more accurate inferences on, for example, marker locations. We describe a method for integrating (possibly conflicting) experimentally derived genetic maps. It assumes a fully probabilistic model that describes the relationship between experimentally derived genetic maps and the integrated map. The model views experimentally derived maps for a given species' chromosome as noisy realisations of a single "true" map, where the noise consists of possible linear distortions and measurement error on the marker locations. Bayesian statistical inference methodology is then used to infer the integrated map (the "true" map) and its attendant uncertainties in the marker locations by using data from a number of experimentally determined genetic maps. The method is shown to work well on simulated data and is used to integrate linkage maps of Pig chromosome 6 and also linkage and radiation hybrid maps of Cow chromosome 1. PMID- 20583929 TI - Discretization of time series data. AB - An increasing number of algorithms for biochemical network inference from experimental data require discrete data as input. For example, dynamic Bayesian network methods and methods that use the framework of finite dynamical systems, such as Boolean networks, all take discrete input. Experimental data, however, are typically continuous and represented by computer floating point numbers. The translation from continuous to discrete data is crucial in preserving the variable dependencies and thus has a significant impact on the performance of the network inference algorithms. We compare the performance of two such algorithms that use discrete data using several different discretization algorithms. One of the inference methods uses a dynamic Bayesian network framework, the other-a time and state-discrete dynamical system framework. The discretization algorithms are quantile, interval discretization, and a new algorithm introduced in this article, SSD. SSD is especially designed for short time series data and is capable of determining the optimal number of discretization states. The experiments show that both inference methods perform better with SSD than with the other methods. In addition, SSD is demonstrated to preserve the dynamic features of the time series, as well as to be robust to noise in the experimental data. A C++ implementation of SSD is available from the authors at http://polymath.vbi.vt.edu/discretization . PMID- 20583930 TI - Diversity and clinical science in obstetrics and gynecology. PMID- 20583931 TI - Parity and low birth weight and preterm birth: a systematic review and meta analyses. AB - OBJECTIVE: To systematically review the risks of pregnancy outcomes among women of different parity. MATERIAL AND METHODS: Electronic databases were searched for studies, in English language, in which primary objective was to assess association between parity and pregnancy outcomes. Meta-analyses were performed and unadjusted odds ratios (ORs) and mean differences along with 95% confidence interval (CI) were calculated. MAIN OUTCOME MEASURES: Low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), birth weight, and gestational age. RESULTS: Forty-one studies, most with moderate risk of bias were included. Nulliparity was associated with increased unadjusted odds of LBW (OR 1.41, 95% CI 1.26, 1.58) and SGA (OR 1.89, 95% CI 1.82, 1.96) and reduction in birth weight (weighted mean difference -282 g, 95% CI -486, -79 g) but not PTB (OR 1.13, 95% CI 0.96, 1.34). Grand multiparity and great grand multiparity were not associated with LBW (OR 1.10, 95% CI 0.95, 1.32 and OR 0.92, 95% CI 0.78, 1.09) or PTB (OR 0.96, 95% CI 0.77, 1.19 and OR 1.32, 95% CI 0.61, 2.83). CONCLUSIONS: Nulliparity was associated with a significantly increased unadjusted risk of LBW/SGA birth, whereas grand multiparity and great grand multiparity were not associated with increased risk of pregnancy outcomes. PMID- 20583932 TI - Outcomes of cystocele repair surgery in relation to different anesthesia methods. AB - OBJECTIVE: To investigate outcomes of cystocele surgery by different anesthesia and evaluation of patient satisfaction. DESIGN: Population-based, retrospective study. SETTING: All clinics that included patients in the Swedish National Register for Gynecological Surgery. POPULATION: A total of 1,364 women who underwent cystocele repair from January 2006 to June 2009. METHODS: The study population was retrieved from the Register among women who had surgery and where there was complete information on concurrently used anesthesia. Clinical variables were compared. Peri- and postoperative complications were investigated. Multivariate logistic regression analysis was applied to identify independent factors for patient satisfaction. MAIN OUTCOME MEASURES: Time to recovery, complications and patient satisfaction. RESULTS: We found a wide variation between hospitals with respect to use of local anesthesia (LA) in cystocele surgery. Length of hospital stay, duration of use of postoperative painkilling drugs, and patient-reported time to return to daily activity were shorter in the LA group compared to the other two anesthesia forms. Postoperative complications did not differ between groups. Age (> or =50 years) and patient-reported complications were independent factors related to patient satisfaction (OR 3.05; 95%CI 1.36-6.82 and OR 0.21; 95%CI 0.12-0.36, respectively). Patient satisfaction did not relate to methods of anesthesia. CONCLUSION: Cystocele surgery can be performed safely using LA thus limiting the use of more invasive anesthesia methods. LA benefits patients and should be increasingly used. PMID- 20583933 TI - No increased risk of adverse pregnancy outcomes in women with urinary tract infections: a nationwide population-based study. AB - OBJECTIVE: To examine the risk of adverse pregnancy outcomes (low birthweight (LBW), preterm birth, and small-for-gestational age (SGA)) in pregnant women with urinary tract infections (UTIs) using a 3-year nationwide population-based database, simultaneously taking characteristics of infant and mother into consideration. Design. Retrospective cross-sectional study. SETTING: Taiwan. SAMPLE: In total, 42,742 mothers with UTIs and 42,742 randomly selected mothers were included. METHODS: Conditional logistic regression analyses to investigate the risk of LBW, preterm birth, and SGA, comparing these two cohorts. MAIN OUTCOME MEASURES: LBW, preterm birth, and SGA. RESULTS: Pearson chi(2) tests show that there were significant differences in the prevalence of preterm births (<37 weeks) (7.2%, 7.7 vs. 8.3%, p = 0.006) and SGA infants (<10th percentile) (16.1%, 16.5 vs. 18.9%, p = 0.003) among pregnant women who were not exposed to UTIs, those exposed to antepartum non-pyelonephritic UTIs and those exposed to pyelonephritis. However, after adjusting for potential confounding factors, the odd ratios (ORs) for LBW were not statistically significant for mothers exposed to antepartum non-pyelonephritic UTIs, compared to women who were not diagnosed with UTIs; neither for <34 or <37 weeks nor SGA <10th percentile and <2 SDs. Similarly, compared to women who were not exposed to UTIs, the adjusted ORs for LBW, <34 weeks, <37 weeks, SGA <10th centile, and <2 SD did not reach a significant level for mothers exposed to pyelonephritis. CONCLUSIONS: Women exposed to antepartum pyelonephritis or non-pyelonephritic UTIs were not at increased risk of having LBW, preterm, and SGA babies, compared to mothers who did not experience UTIs. PMID- 20583934 TI - Comparison of single and multiple dose methotrexate therapy for unruptured tubal ectopic pregnancy: a prospective randomized study. AB - OBJECTIVE: To compare the success rates of single and multiple dose methotrexate protocols for the treatment of unruptured tubal ectopic pregnancy. DESIGN: Prospective randomized controlled trial. SETTING: Maternity and teaching hospital in Turkey. POPULATION: One hundred twenty women treated with methotrexate therapy for unruptured tubal ectopic pregnancy. METHODS: Sixty-two women received a single dose and 58 received a multiple dose methotrexate regimen. MAIN OUTCOME MEASURES: Success rate of methotrexate therapy (women successfully treated with one injection and women who completed four doses). RESULTS: In the single dose group, treatment was considered successful in 50 women (80.6%), whereas in the multiple dose group, 52 women (89.7%) responded to treatment (p = 0.21; OR 0.90, 95%CI 0.77-1.05). The average number of days required for human chorionic gonadotropin (hCG) levels to fall below 5 mU/mL was longer in the single dose (22.3 +/- 7.6) compared with the multiple dose group (18.3 +/- 10.7) (p = 0.03). In the single dose group fewer or 17 women (24.7%) experienced side-effects compared to 28 (48.3%) of those who had multiple doses (p = 0.02, OR 0.57, 95%CI 0.35-0.92). CONCLUSION: A multiple dose methotrexate regimen for the treatment of unruptured tubal ectopic pregnancy is not more effective than a single dose one. In addition, multiple doses may cause more side-effects, but the time for hCG levels to fall below 5 mU/mL is shorter. PMID- 20583935 TI - Cesarean delivery in Finland: maternal complications and obstetric risk factors. AB - OBJECTIVE: To assess the rate of maternal complications related to cesarean section (CS) and to compare morbidity between elective, emergency and crash emergency CS. To establish risk factors associated with maternal CS morbidity. DESIGN: A prospective multicenter cohort study. SETTING: Twelve delivery units in Finland. POPULATION: Women delivering by CS (n = 2,496) during a 6 months period in the study hospitals. METHODS: Data on pregnant women, CS, and maternal recovery during the hospital stay was collected prospectively on report forms. The complication rates by different CSs were calculated, and factors associated with morbidity were analyzed by odds ratios (OR). MAIN OUTCOME MEASURES: Maternal complication rates in different types of CS. The association of risk factors with morbidity. RESULTS: About 27% of women delivering by CS had complications; 10% had severe complications. The complication rate was higher in emergency CS than in elective CS, and highest in crash-emergency CS. Significant independent risk factors for maternal morbidity were emergency CS and crash-emergency CS compared to elective CS (OR 1.8; 95% confidence interval (CI) 1.5-2.2), pre-eclampsia (OR 1.5; CI 1.1-2.0), maternal obesity (OR 1.4; CI 1.1-1.8) and maternal increasing age (OR 1.1; CI 1.03-1.2 per each 5 years). CONCLUSIONS: Maternal complications are frequent in CS, and although performing CS electively reduces the occurrence of complications, the frequency is still high. The complication rate depends on the degree of emergency, and increases with maternal obesity, older age and pre eclampsia. PMID- 20583936 TI - High cesarean prevalence in a national population-based study in Brazil: the role of private practice. AB - BACKGROUND: Excessive use of cesarean sections (CSs) is a serious problem worldwide. OBJECTIVE: To estimate the frequency and identify factors associated with cesarean deliveries in Brazil. DESIGN: Cross-sectional study conducted in 2006-2007 as part of the third edition of the Children's and Women's National Demographic and Health Survey. SETTING: Brazil. SAMPLE: Brazilian women in reproductive age. METHODS: Socioeconomic and demographic data were utilized, including maternal age, education level, per capita income, skin color, smoking habit, marital status, age at first delivery, parity, and type of prenatal services. MAIN OUTCOME MEASURES: Adjusted estimate of the prevalence ratios of the type of delivery performed (cesarean or vaginal). RESULTS: Cesarean prevalence was 43.9% (95% CI: 40.9-46.9), 68.7% for women who had per capita income greater than US$ 125 per month, and 77.2% for those who had attended private or privately insured prenatal services. In the adjusted analysis, the variables that presented significant prevalence ratios (95% confidence interval) were macro-region [southeast = 1.45 (1.21-1.73); south = 1.48 (1.24-1.77), and midwest = 1.43 (1.21-1.71)], maternal age above 25 years [26-30 years = 1.57 (1.25-1.97); > or = 31 years = 1.77 (1.39-2.27)], education levels > or = 9 years (PR = 1.86, 95% CI: 1.55-2.23), and having attended private or privately insured prenatal services (PR = 1.87, 95% CI: 1.65-2.12) and parity [primipara = 1.87 (1.47-2.36)]. CONCLUSIONS: CS rates are generally very high in Brazil. They are significantly higher than the average among women attending private/insured antenatal care, among the highly educated, and in provinces with higher socioeconomic levels. PMID- 20583937 TI - Effects of intrapartum epidural analgesia at high altitudes: maternal, fetal, and neonatal outcomes. A randomized controlled trial of two formulations of analgesics. AB - OBJECTIVES: To investigate whether intrapartum epidural analgesics (bupivacaine or ropivacaine) have an influence (safety and efficacy) on mothers, fetuses, or newborns at high altitudes (2,200 m above the sea level). DESIGN: Prospective randomized trial. SETTING: A tertiary referral hospital in Aseer region, Saudi Arabia. POPULATION: Eighty parturient women with normal full term pregnancy (37 40 weeks) were randomly allocated to a group receiving epidural bupivacaine 0.125% and the other receiving ropivacaine 0.2%, with fentanyl 100 microg given to both groups. METHODS: Intra- and postpartum clinical management of the pregnant women and newborns and fetal Doppler assessments were performed. MAIN OUTCOME MEASURES: Severity of pain, onset and duration of analgesia, and occurrence of motor blockade were primary outcomes. Progress of labor, need for oxytocin augmentation, mode of delivery, and neonatal condition were secondary outcomes. RESULTS: Demographic, labor characteristics, and neonatal outcomes of the two groups were comparable. The onset of analgesia was relatively more rapid for ropivacaine group (p = 0.067). Duration of analgesia after the first bolus dose was longer and the need for supplemental epidural analgesic doses was lesser in the bupivacaine group (p = 0.041 and 0.045, respectively). In both groups, the fetal umbilical and middle cerebral artery pulsatility indices showed significant change when compared to the baseline of the same group. CONCLUSION: At high altitudes, no major advantage was found for epidural ropivacaine over bupivacaine in addition to fentanyl for labor analgesia and no harmful effects of the medications were found on mothers, fetuses, or newborns. PMID- 20583938 TI - Physical activity during pregnancy in obese and normal-weight women as assessed by pedometer. AB - OBJECTIVE: To compare physical activity as assessed by a pedometer in obese and normal-weight pregnant women at different gestational ages. To evaluate the use of a pedometer in pregnancy. DESIGN: Cross-sectional study. SETTING: Department of obstetrics and gynecology in a university hospital in Copenhagen. POPULATION: 338 pregnant women, 175 normal-weight women with body mass index (BMI) 20-25 kg/m(2) and 163 obese women with BMI > or = 30 kg/m(2). METHODS: Physical activity was assessed by a pedometer (Yamax Digiwalker SW-700/701) on seven consecutive days in six different groups: normal-weight or obese at gestational ages 11-13, 18-22, and 36-38, and expressed as median number of daily steps during a whole week, working days, and weekends. MAIN OUTCOME MEASURES: Relation between BMI and physical activity during pregnancy and compliance with wearing the pedometer. RESULTS: Noncompliance was more frequent in obese than in normal weight women (19 vs. 10%, p < 0.001). Physical activity was lower in obese women at all gestational ages (6,482, 7,446, 4,626 steps/day in obese vs. 7,558, 8,865, 6,289 steps/day in normal-weight, p < 0.05-0.11). The greatest difference between obese and normal-weight women was seen during weekends. The level of physical activity was higher in both groups at mid-gestation than during earlier and later gestational ages. CONCLUSION: Physical activity in pregnant women can be assessed by the pedometer and the method was well accepted by the women; however, the compliance was lower in the obese. The level of physical activity differs between different gestational groups and is lower in obese than in normal-weight women, especially during leisure time. PMID- 20583939 TI - Paget's disease of the vulva: evaluation of recurrence relative to symptom duration, volumetric excision of lesion, and surgical margin status. AB - We analyzed recurrences with regard to symptom duration, volumetric excision, and surgical margin in 11 women with Paget's disease of the vulva. Data concerning demographics, surgical margin, and current state were collected. In addition, the three-dimensional excisional skin and lesion size was determined from surgical and pathology reports. Recurrence was observed in 6 women where the symptom duration was longer than in those without recurrence (33 vs. 11 months, p < 0.02). During the initial operation, the fraction of removed normal skin was 85.3% in all the women, and 79.8% (range 67-97%) in those with recurrence and 92.0% (range 86-96%) in those without (p < 0.04). Of 11 women, 8 had positive margins of whom 4 developed recurrence and 4 did not. Of the 3 patients with negative margins, 2 experienced recurrence but the third did not (p = 0.58). Recurrence was not associated with positive margins, but correlated with symptom duration and volumetric excision. PMID- 20583940 TI - Vaginal involvement in genital erosive lichen planus. AB - A specialized Vulva Clinic with dedicated gynecologists and dermatologists was established in Oslo, Norway, in 2003. Fifty-eight women referred to the clinic in 2003-2009 were diagnosed with genital erosive lichen planus. All patients filled out a questionnaire. Gynecological examination, including vaginal inspection, was performed, if necessary in general anesthesia. Median age at symptom start was 51 years (range 17-78 years) with 15 women (26%) being younger than 40 years old. Sexual abstinence was reported by 36 women and dyspareunia by another 10. On examination, vaginal involvement was seen in 49 women, including vaginal synechiae in 29 and total obliteration of the vagina in 9. Of 56 women treated with topical corticosteroids for at least three months, two had complete response and 36 partial responses. Similarly, of 22 women treated with tacrolimus, three had complete and six partial response. We conclude that vaginal involvement is more common in genital erosive lichen planus than previously reported. PMID- 20583941 TI - Fetal cardiac arrhythmia during bupropion use. PMID- 20583945 TI - Speech perception performance as a function of stimulus pulse rate and processing strategy preference for the Cochlear Nucleus CI24RE device: relation to perceptual threshold and loudness comfort profiles. AB - Current cochlear implants can operate at high pulse rates. The effect of increasing pulse rate on speech performance is not yet clear. Habituation to low rates may affect the outcome. This paper presents the results of three subsequent studies using different experimental paradigms, applying the Nucleus CI24RE device, and conducted by ten European implant teams. Pulse rate per channel varied from 500 to 3500 pulses per second with ACE and from 1200 to 3500 pps with CIS strategy. The results showed that the first rate presented had little effect on the finally preferred rate. Lower rates were preferred. The effect of pulse rate on word scores of post-linguistic implantees was small; high rates tended to give lower scores. However, there were no significant differences between the word scores across subjects if collected at the individually preferred pulse rate. High pulse rates were preferred when the post-implantation threshold was low. PMID- 20583946 TI - The interface of population-based cancer registries and biobanks in etiological and clinical research--current and future perspectives. AB - BACKGROUND: The availability of quality assured, population-based cancer registries and biobanks with high quality samples makes it possible to conduct research on large samples sets with long follow-up within a reasonable time frame. Defined quality for both cancer registries and biobanks is essential for enabling high quality biobank-based research. Recent networking projects have brought these infrastructures together to promote the combined use of cancer registries and biobanks in cancer research. MATERIALS AND METHODS: In this report we review the current status and future perspectives of cancer registries and biobanks and how the interface between them should be developed to optimally further cancer research. RESULTS AND DISCUSSION: Major conclusions for future improvements are that the research exploiting cancer registries and biobanks, and the research that is building and optimising the infrastructure, should evolve together for maximally relevant progress. Population-based and sustainable biobanks that continuously and consecutively store all samples ("Biological registries") under strict quality control are needed. There is also a need for increased education, information and visibility of the interdisciplinary sciences required for optimal exploitation of these resources. PMID- 20583947 TI - A brain-computer interface for long-term independent home use. AB - Our objective was to develop and validate a new brain-computer interface (BCI) system suitable for long-term independent home use by people with severe motor disabilities. The BCI was used by a 51-year-old male with ALS who could no longer use conventional assistive devices. Caregivers learned to place the electrode cap, add electrode gel, and turn on the BCI. After calibration, the system allowed the user to communicate via EEG. Re-calibration was performed remotely (via the internet), and BCI accuracy assessed in periodic tests. Reports of BCI usefulness by the user and the family were also recorded. Results showed that BCI accuracy remained at 83% (r = -.07, n.s.) for over 2.5 years (1.4% expected by chance). The BCI user and his family state that the BCI had restored his independence in social interactions and at work. He uses the BCI to run his NIH funded research laboratory and to communicate via e-mail with family, friends, and colleagues. In addition to this first user, several other similarly disabled people are now using the BCI in their daily lives. In conclusion, long-term independent home use of this BCI system is practical for severely disabled people, and can contribute significantly to quality of life and productivity. PMID- 20583948 TI - Preliminary assessment of dynamic contrast-enhanced CT implementation in pretreatment FDG-PET/CT for outcome prediction in head and neck tumors. AB - BACKGROUND: Recently published data show some controversy concerning the impact of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in predicting head and neck tumors (HNT) outcome. Assessment of tumor blood supply parameters using dynamic contrast-enhanced CT (DCE-CT) may deliver additional information concerning this important question. PURPOSE: To evaluate the contribution of DCE-CT implemented in pretherapeutic FDG-PET/CT protocol for prognosis prediction in patients with HNT. MATERIAL AND METHODS: Ten consecutive patients (median age 50 years, range 47-74 years) with histologically proven HNT underwent FDG-PET/CT with DCE-CT before treatment. FDG uptake was measured by maximum standardized uptake value (SUV(max)). Relative tumor blood volume (rTBV) was determined from DCE-CT using Patlak analysis. Intratumoral heterogeneity was assessed by means of lacunarity analysis. Obtained values were compared with time to-progression and overall survival. PET and DCE-CT images were compared on a pixel-by-pixel basis using Pearson coefficient of correlation. RESULTS: Three patients with lower FDG uptake (SUV(max): 8+/-1) and five patients with higher FDG uptake (SUV(max): 15+/-4, P=0.004) were free of local recurrence for 24 months. Two groups of patients with significantly differing lower (group A: 0.37+/-0.02, n=6) and higher (group B: 0.52+/-0.01, n=4; P<0.01), tumor heterogeneity (lacunarity) were identified. Corresponding mean rTBV was higher in group A (9.6+/-1.8 ml/100 ml) than in group B (6.2+/-0.6 ml/100 ml). All six patients with homogeneous tumor blood supply (lower lacunarity) and higher rTBV were free of local recurrence during 24 months, while two of four patients with heterogeneous tumor blood supply (higher lacunarity) and lower rTBV died during follow-up due to tumor relapse. A weak correlation between FDG-PET and DCE-CT rTBV was observed (R(2)=0.1). CONCLUSION: FDG-PET/CT and DCT-CT are complementary methods for surveillance assessment in patients with HNT. Implementation of DCE CT in the pretreatment FDG-PET/CT protocol may improve tumor outcome prediction. PMID- 20583949 TI - Evaluation of the potential for pharmacokinetic and pharmacodynamic interactions between dutogliptin, a novel DPP4 inhibitor, and metformin, in type 2 diabetic patients. AB - OBJECTIVE: Dutogliptin is a novel, orally available, potent, and selective DPP4 inhibitor that improves glycemic control in type 2 diabetic patients. The objective of this study was to evaluate the potential pharmacokinetic and pharmacodynamic interactions, as well as the tolerability, of dutogliptin and metformin alone and in combination in type 2 diabetic patients. METHODS: This was a single-center, randomized, open-label, 3-way, crossover study in type 2 diabetic patients. All patients received three treatment regimens, each of 5 days duration in order to reach steady state: 400 mg once daily of dutogliptin (the anticipated clinical dose); 1000 mg metformin twice daily (maximum effective clinical dose); and concomitant administration of 400 mg dutogliptin once daily and 1000 mg metformin twice daily. RESULTS: Co-administration of dutogliptin and metformin did not alter the pharmacokinetics of either agent. The geometric mean ratio, GMR (dutogliptin + metformin/dutogliptin) of the area under the plasma concentration-time curve (AUC(0-24h)) at steady state was 0.91 (90% CI: 0.79 1.06; p = 0.29); the GMR of the maximum plasma concentrations (C(max)) was 0.95 (90% CI: 0.76-1.19; p = 0.70); the time to maximum plasma concentrations (T(max)) was essentially the same for dutogliptin with or without metformin. The GMR (dutogliptin + metformin/metformin) of AUC(0-12h) at steady state was 0.99 (90% CI: 0.84-1.17; p = 0.93); the GMR of C(max) was 0.91 (90% CI: 0.79-1.04; p = 0.18); T(max) was comparable for metformin with or without dutogliptin. Metformin added to dutogliptin had no effect on plasma DPP4 inhibition. All three treatment regimens were well tolerated. CONCLUSIONS: In this small, multiple dose study, the steady state pharmacokinetics of either dutogliptin or metformin were not altered by co-administration of the two agents. Dutogliptin and metformin were well tolerated either alone or in combination and co-administered metformin did not alter the ex vivo DPP4 inhibition by dutogliptin. There is no need to consider pharmacokinetic and pharmacodynamic interactions when determining the dosage of either agent for co-administration. A phase 3 clinical trial is underway to provide more definitive data on the safety and efficacy of dutogliptin administered on a background of metformin treatment. PMID- 20583950 TI - Using telepractice in parent training in early autism. AB - There is a growing body of literature indicating that intense early intervention is current best practice for treating children with autism spectrum disorders (ASD). Several studies demonstrate the effectiveness of parents as agents of intervention in the child's home environment. However, this approach requires intense one-on-one supervision by highly trained professionals. Consequently, there is a significant gap between the intensive service requirements for children with ASD and the available resources to provide these services. In the current pilot study, the use of remote technology, telepractice, is evaluated as a tool for coaching parents of two children found to have ASD. Two clinical models of intervention are compared: a traditional model of twice-weekly speech and language therapy sessions (traditional clinical model) and a model where a once-a-week clinical session is followed by a home-based session administered by the parents and remotely supervised and coached by the clinician (clinic/telepractice model). Results suggest that gains obtained in traditional therapy can be maintained and even exceeded in a treatment model that uses telepractice. Parents reported that they perceived telepractice sessions to be as valuable as those delivered directly by the clinician, felt comfortable using the technology, and were willing to continue intervention with their children at home. These preliminary results suggest that use of telepractice holds promise for reducing the demands on available resources of service for this population. A study with a larger population is currently underway including cost-benefit analyses to examine the implications for such a treatment model to its users and to the healthcare system. PMID- 20583951 TI - Safety of telemental healthcare delivered to clinically unsupervised settings: a systematic review. AB - The safety of telemental healthcare delivered to clinically unsupervised settings, such as a personal residence, must be established to inform policy and further the dissemination of telemental health programs. The aim of this article is to provide an overview of safety issues associated with telemental healthcare and, through a systematic literature review, evaluate the safety of telemental healthcare delivered to unsupervised settings. The review resulted in a total of nine studies that specifically evaluated the delivery of telemental healthcare to unsupervised settings. Six of the nine studies reviewed explicitly described safety plans or specific precautions that could be used if necessary. Two of the nine studies reported events that required the researchers to use safety procedures to effectively respond to concerns they had regarding participant safety. In both of these studies, the issues were resolved with prescribed safety procedures. Recommendations and future directions for the development and evaluation of safety protocols are discussed. PMID- 20583952 TI - A study on an information security system of a regional collaborative medical platform. AB - The objective of this study was to share the experience of building an information security system for a regional collaborative medical platform (RCMP) and discuss the lessons learned from practical projects. Safety measures are analyzed from the perspective of system engineering. We present the essential requirements, critical architectures, and policies for system security of regional collaborative medical platforms. PMID- 20583953 TI - Long-term treatment with a "Yang-invigorating" Chinese herbal formula, Wu-Zi-Yan Zong-Wan, reduces mortality and liver oxidative damage in chronic alcohol intoxicated rats. AB - Long-term alcohol consumption has been reported to increase oxidative stress in multiple organs and accelerate the aging process. A previous study in our laboratory has shown that Wu-Zi-Yan-Zong-Wan (WZ), a "Yang-invigorating" Chinese herbal formula, protected against ethanol-induced toxicity in HepG2 cells transfected to express human CYP2E1, presumably by enhancing mitochondrial antioxidant status and functional ability. The present study aims to investigate whether WZ extract treatment can afford protection against chronic ethanol induced oxidative stress (a major risk factor of aging) and mortality in rats. The effect of the extract (1.8 g, 4.5 g, and 9 g raw materials/kg per day) on chronic ethanol hepatotoxicity was investigated in rats receiving steady intragastric infusion of ethanol-containing liquid diet. The results showed that long-term (42 days) herbal co-treatment protected against chronic ethanol-induced mortality and hepatotoxicity and in rats, as evidenced by decreased plasma transaminases activities. The extract also suppressed the pathological development of fatty liver, as assessed by histopathological examination and the ratio of liver weight to body weight. The hepatoprotection afforded by the extract was associated with decreases in the extents of reactive oxygen species production, lipid peroxidation, and oxidative modification of proteins, as well as the reversal of altered mitochondrial reduced glutathione level. The results suggest that the suppressive effect of WZ on chronic ethanol-induced oxidative stress and mortality may be attributed to the antioxidant action, particularly in mitochondria. PMID- 20583954 TI - The effect of age on the efficacy of human mesenchymal stem cell transplantation after a myocardial infarction. AB - OBJECTIVE: Clinical trials of cardiac cell therapy have indicated limited benefits in aging patients, even though preclinical studies using young animals consistently reported significant improvements. Animal studies have demonstrated reduced efficacy of donor cells isolated from older individuals. Here, we evaluated the effects of donor age on the function of human mesenchymal stem cells (hMSCs) in the context of cell therapy for ischemic cardiomyopathy. METHODS: In vitro, we compared the growth and clonogenic potential of hMSCs isolated from young or old patients (1-5 vs. 50-70 years old). In vivo, we injected young or old hMSCs (2.0 x 10(6)) (or medium) into the infarcted myocardia of immunosuppressed rats immediately after coronary artery ligation (myocardial infarction [MI]). We assessed cardiac function (echocardiography) at 1, 2, and 4 weeks after MI, and myocardial matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) levels at 1 week. RESULTS: In vitro, growth and colony-forming unit fibroblast (CFU-F) formation were markedly diminished in old hMSCs (p < 0.001 and p < 0.05, respectively, vs. young). In vivo, compared with old hMSCs or medium, young hMSCs best preserved ejection fraction, fractional shortening (p < 0.05), and left ventricular end-diastolic and end-systolic volumes (p < 0.01). Recipients of young hMSCs also exhibited increases in vascular density and TIMP-3 protein levels and activity (p < 0.05), and decreases in MMP protein levels and activity (p < 0.05). CONCLUSIONS: The regenerative capacity of hMSCs was significantly influenced by age. Transplanting young hMSCs improved functional outcomes after an MI by preventing matrix degradation and promoting angiogenesis. The clinical implication is that aged patients require an optimized source of stem cells for treatment. PMID- 20583955 TI - Extended retroperitoneal necrotizing fasciitis with genital involvement, resembling fournier gangrene. AB - BACKGROUND: Necrotizing fasciitis is a serious infection that originates in the subcutaneous tissues. Although many reports have been published about necrotizing infections of other anatomical sites, retroperitoneal necrotizing soft tissue infection is a rare entity that has been described in only a few case reports. The etiology and clinical course of retroperitoneal necrotizing fasciitis can be variable and it is often difficult to identify the etiology of the infective process. CASE REPORT: We report a 58-year-old man with rapidly progressive, gas producing, necrotizing inflammation in the retroperitoneum, complicated with genital involvement resembling Fournier gangrene. The patient was managed successfully by aggressive drainage, debridement, and sequential laparotomies to track and control the extensive necrosis of the retroperitoneum and perineum, in addition to systemic care to control sepsis. After his general condition stabilized, early rectosigmoid adenocarcinoma was identified and resected curatively. He remained well at follow up, six months after discharge. RESULTS: In retrospect, the trigger of the disease process was unclear. Although it was believed possibly to be due to the colon lesion, adenocarcinoma of the rectosigmoid colon was identified and the patient was managed successfully. CONCLUSIONS: Similar to necrotizing infections at other anatomical sites, early diagnosis and timely surgical intervention and systemic antimicrobial therapy are mandatory for treating patients with retroperitoneal necrotizing fasciitis. PMID- 20583956 TI - Clinical update on the use of moxifloxacin in the treatment of community-acquired complicated intraabdominal infections. AB - BACKGROUND: Community-acquired complicated intraabdominal infections (cIAIs) present problems for clinicians and have substantial impact on hospital resources. Because of the polymicrobial nature of these infections, successful management of cIAIs depends on timely and appropriate use of antisepsis and antiinfective strategies. METHODS: The literature pertinent to this article was reviewed. RESULTS: The Surgical Infection Society and the Infectious Disease Society of America guidelines recommend a variety of single and combined antimicrobial therapies, including fluoroquinolone therapy, for prophylactic and definitive treatment of cIAIs with different severities. Moxifloxacin, a fluoroquinolone, demonstrates a broad spectrum of antimicrobial (including anaerobic) activity, good tissue penetration into the gastrointestinal tract, and a good tolerability profile. Clinical data also have demonstrated that moxifloxacin is effective as monotherapy for patients with cIAIs. This review identifies the clinical issues impacting antimicrobial selection in cIAI and discusses data on the role of moxifloxacin in light of the current guidelines for management of these patients. CONCLUSION: Moxifloxacin provides clinicians with a convenient monotherapy option for the treatment of mild-to-moderate cIAIs. PMID- 20583957 TI - Nonsurgical treatment of pyomyoma in the postpartum period. AB - BACKGROUND: Only 13 cases of pyomyoma related to pregnancy have been described since 1945. Treatment consists of hysterectomy, which exposes critically ill patients to operative risks and induces infertility. CASES: Three cases of pyomyoma in the postpartum period are described. Treatment using computed tomography-guided drainage was realized successfully in two cases. CONCLUSION: Therapy via drainage and lavage of pyomyoma is a viable option to preserve patient fertility. In the absence of a proper response to this treatment, total abdominal hysterectomy is the treatment of choice. PMID- 20583958 TI - Depressive disorders among cohorts of women veterans with diabetes, heart disease, and hypertension. AB - OBJECTIVES: To compare the rates of major and minor depression in cohorts of women veterans with diabetes or heart disease or hypertension and examine variations in these rates by demographic, socioeconomic, and health status among these women. METHODS: This was a retrospective cross-sectional analysis of fiscal year 2002 and 2003 data on 13,430 women veterans with diabetes or heart disease or hypertension who were diagnosed with depression and used Veteran Health Administration (VHA) clinics. International Classification of Diseases, 9th ed. Clinical Modification codes from merged VHA and Medicare claims files were used to identify diabetes, heart disease, hypertension, and depression. Chi-square tests and multinomial logistic regressions were used to characterize women veterans with major and minor depression. RESULTS: Of all the women veterans diagnosed with diabetes or heart disease or hypertension and using the VHA clinics, 27% were diagnosed with depression. Of these 13,430 women with any depression, 60% were diagnosed with minor depression and 40% had major depressive disorders (MDD). Compared to major depression, minor depression was significantly more likely among women veterans who were older, without any other psychiatric condition and substance use disorders. CONCLUSIONS: Minor depression is highly prevalent among women veterans with complex chronic illness, such as diabetes or heart disease or hypertension (i.e., women at risk or with cardiovascular conditions), suggesting a need to closely monitor these women to reduce the risk of major depression. Some subgroups of women were more likely to have minor depression than major depression; studies that exclusively focus on major depression will selectively miss these subgroups of women veterans. PMID- 20583959 TI - Self-reported mental health status and recent mammography screening. AB - OBJECTIVE: The purpose of this study was to assess the association between self perceived mental health status and mammography screening in Kentucky. METHODS: Using a cross-sectional design, we examined survey data from the 2002 Kentucky Behavioral Risk Factor Surveillance System (BRFSS) for women aged > or =40. Mental health status was measured by the reported number of days that mental health was not good; the number of days feeling sad, blue, or depressed; and the number of days feeling worried, tense, or anxious. The outcome was mammography within the last 2 years. Three logistic regression analyses were performed, one with each of the mental health status questions as the predictor variable. Analyses controlled for age, race, marital status, education, income, and health insurance status. RESULTS: The numbers of poor mental health days, depressed days, and anxious days were found to be significant or near-significant predictors of recent mammography. Odds ratios (ORs) comparing women reporting 30 poor mental health days, depressed days, or anxious days with similar women reporting zero days were estimated to be 1.68 (95% confidence interval [CI] 1.08 2.63), 1.49 (0.93-2.40), and 1.46 (0.96-2.23), respectively. CONCLUSIONS: Self reported poor mental health, depression, and anxiety may be associated with nonreceipt of regular mammography screening. How mental health symptoms and self reported poor mental health status contribute to decreased mammography screening should be explored. PMID- 20583960 TI - Urethral strictures and bipolar transurethral resection in saline of the prostate: fact or fiction? AB - PURPOSE: To compare the incidence of urethral strictures after monopolar transurethral resection of the prostate (TURP) and bipolar transurethral resection in saline (TURIS) for symptomatic benign prostatic hyperplasia. PATIENTS AND METHODS: Between January 2005 and January 2009, 518 patients with symptomatic benign prostate hyperplasia underwent either monopolar or bipolar resection. In a randomized trial, the incidence of urethral strictures after both treatment modalities was analyzed. RESULTS: Over 48 months, 255 patients were treated with conventional TURP and 263 patients with TURIS. Patient related, operation, and hospitalization characteristics were similar in both groups. After a mean follow-up of 32.1 months (range 50-7 months), the incidence of urethral strictures was 2.4% in the TURP group. After a comparable period of 31.4 months (range 50-7 months), the incidence in the TURIS group was 1.5%. No statistically significant difference was obtained (P = 0.539). These values were compared with the results of other randomized controlled trials with the same or other bipolar technology. No statistically significant difference in urethral structures was noticed between monopolar and bipolar resections (P = 0.739). CONCLUSIONS: With a stricture incidence of 1.5%, bipolar transurethral prostate resection has a low stricture rate, comparable with monopolar TURP (2.4%). PMID- 20583961 TI - Dissemination of cefotaxime-M-producing Escherichia coli isolates in poultry farms, but not swine farms, in China. AB - The objective of this study was to investigate the distribution of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli isolates in swine and poultry farms in China. Rectal or cloaca swabs of swine and chicken were collected from four province-level regions of China, and E. coli isolates were recovered and tested for antimicrobial susceptibility. The isolates producing ESBLs were further characterized by pulsed-field gel electrophoresis (PFGE) and sequence analysis of genes encoding beta -lactamases and class I integrons. In total, 156 and 224 E. coli isolates were recovered from rectal swabs of four swine farms and cloaca swabs of six chicken farms, respectively. Prevalence of resistant isolates was higher in chicken than in swine. Fifty-six isolates producing ESBLs were identified from chicken samples, but no ESBL-producing isolates were identified from swine samples. Of 56 ESBL-producing isolates, 54 isolates contained cefotaxime (CTX)-M type beta-lactamases, including bla(CTX-M 14) (n = 24), bla(CTX-M-65) (n = 13), bla(CTX-M-55) (n = 10), bla(CTX-M-24) (n = 3), bla(CTX-M-3) (n = 2), bla(CTX-M-15) (n = 1), and bla(CTX-M-64) (n = 1). Among 54 E. coli isolates containing bla(CTX-M), 11 PFGE clusters and 42 PFGE patterns were identified. More importantly, more than three-fourth of the ESBL-producing isolates in chicken were also resistant to ciprofloxacin. Our data demonstrated that chicken had become an important reservoir of bla(CTX-M) in China. Detailed molecular comparison of plasmids and genomes of isolates from various sources will help to better define the transmission dynamics of bla(CTX-M) between humans and food-producing animals. PMID- 20583962 TI - Seasonal prevalence of asymptomatic norovirus infection in Korean children. AB - The prevalence of asymptomatic norovirus (NoV) infection was investigated in children registered for kindergarten in Korea during the winter and summer. Children with no gastrointestinal symptoms, including diarrhea and abdominal pain, during the 2 weeks before and following sample collection were included in this investigation. NoV presence and genetic identification were determined with real-time reverse transcriptase-polymerase chain reaction and conventional nested reverse transcriptase-polymerase chain reaction. The prevalence of NoV in asymptomatic children was 5.5% in the winter and 3.5% in the summer, respectively. GII.4 was the most prevalent NoV genotype, but GII.2 and GI.10 were also found during genetic analysis. This study demonstrates that asymptomatic NoV infection may be an important source of transmission in kindergarten children. PMID- 20583963 TI - Cysteine-string protein's neuroprotective role. AB - Cysteine-string protein (CSP), a member of the DnaJ/Hsp40 family of cochaperones, is critical for maintaining neurotransmitter release and preventing neurodegeneration. CSP likely forms a chaperone complex on synaptic vesicles together with the 70-kDa heat shock cognate (Hsc70) and the small glutamine-rich tetratricopeptide repeat (TPR)-containing protein (SGT) that may control or protect the assembly and activity of SNARE proteins and various other protein substrates. Here, the author summarizes studies that elucidated CSP's neuroprotective role. PMID- 20583964 TI - Reduced-intensity conditioning allogeneic stem cell transplant for relapsed or transformed aggressive B-cell non-Hodgkin lymphoma. AB - The role of reduced-intensity conditioning allogeneic stem cell transplant (RIC allo-SCT) in aggressive B-cell non-Hodgkin lymphoma (NHL) remains a matter of debate. This single-center analysis aimed to assess the potential benefit of RIC allo-SCT in 19 consecutive patients with relapsed or transformed aggressive B cell NHL. Aggressive transformation (primary or secondary) was documented for these patients by pathological examination. In this series, all patients but two (n = 17; 89.5%) could actually receive autologous stem cell transplant (auto-SCT) prior to RIC allo-SCT. At the time of allo-SCT, eight patients (42%) were in first complete remission (CR), six (31.5%) were beyond first CR, and five (26.5%) were in partial remission. With a median follow-up of 32 (range, 3-86) months, nine patients experienced grade 2-4 acute GVHD (47.5%) and 10 patients had extensive chronic GVHD (52.5%). Overall, the incidence of non-relapse mortality was 26% (95% CI, 8-44%). At last follow-up, 12 patients (63%) were in sustained CR. The Kaplan-Meier estimates of progression-free and overall survival rates were 68% and 68%, respectively, at 4 years. We conclude that RIC allo-SCT after auto-SCT is feasible and a potentially efficient therapy for relapsed or transformed aggressive B-cell NHL, warranting further prospective evaluation. PMID- 20583965 TI - Influence of metformin on GLUT1 gene and protein expression in rat streptozotocin diabetes mellitus model. AB - CONTEXT: Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK). Recent findings indicate that some metabolic actions of metformin occur also by AMPK-independent mechanisms. OBJECTIVE: To study the action of metformin on expression of GLUT1 glucose transporter in rat streptozotocin model of diabetes mellitus. MATERIALS AND METHODS: Streptozotocin-induced rats were treated with metformin while monitoring parameters of carbohydrate and lipid metabolism. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time quantitative RT-PCR and immunohistochemistry correspondingly. RESULTS: Metformin treatment decreased glucose concentration, glycated haemoglobin % and improved glucose tolerance. Streptozotocin diabetes provoked increase of both GLUT1 gene and protein expression in kidneys, metformin treatment produced normalization of the GLUT1 expression levels. In the liver, diabetes triggered an increase in GLUT1 protein expression, which was normalized by metformin. CONCLUSION: Metformin is prospective for treatment of diabetic nephropathy. PMID- 20583966 TI - Non-electronic communication aids for people with complex communication needs. AB - Non-electronic communication aids provide one form of augmentative and alternative communication (AAC) for people with complex communication needs. The aim here was to explore non-electronic communication aids as one AAC option and research challenges. This aim was addressed by reviewing funding for the provision of AAC systems, data from an Australian pilot project providing non electronic communication aids, an audit of aided AAC published studies (2000 2009), and discussion of the review literature. Combined, these sources indicate that although there is great demand for non-electronic communication aids, funding schemes, both in Australia and internationally, have focused on electronic communication aids. Such funding has usually failed to meet the total device costs and has not provided for adequate speech-language pathology support. Data from the pilot indicated the demand for non-electronic communication aids, and patterns suggest potential factors that govern the types selected. Despite the high demand for non-electronic aids, the research literature has tended to focus on electronic communication aids, including within intervention studies and addressing design features and long-term outcomes. Concerns about ensuring that AAC systems are chosen according to the assessed needs of individuals are discussed within the context of limitations in outcomes research and appropriate outcome measures. PMID- 20583967 TI - A multi-endpoint evaluation of cytochrome P450 1A2, 2B6 and 3A4 induction response in human hepatocyte cultures after treatment with beta-naphthoflavone, phenobarbital and rifampicin. AB - U.S. FDA and EMEA guidance recommend that the preferred in vitro model for cytochrome P450 induction testing is human hepatocytes coupled with acceptable inducers as controls. However, there are surprisingly few published studies characterizing this model system for dose and time-dependence response to model inducing compounds. The concentration-dependent response and time-course for the induction of CYP1A2, CYP2B6 and CYP3A4 by inducing agents beta-naphthoflavone, phenobarbital and rifampicin, respectively were examined in two or more donors using multiple end-points (mRNA, enzyme activity and Western blot analysis). Depending on the endpoint, exposure time for maximal response of CYP induction potential for the three enzymes ranged from 24 to 72 hours. Of the concentrations of BNF, PB and RIF tested, those which gave the maximal response were found to be 33 uM, > 2 mM and 10 uM, respectively. PMID- 20583968 TI - P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. AB - The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds. Mdr1a/b(-/ ), Mrp4(-/-), and wild-type mice were administered 20 or 40 mg/kg irinotecan, and plasma samples were collected for 6 hours. Irinotecan and SN-38 lactone and carboxylate were quantitated and data were analyzed with nonlinear mixed-effects modeling. Mdr1a/b genotype was a significant covariate for the clearance of both irinotecan lactone and SN-38 lactone. Exposures to irinotecan lactone and SN-38 lactone after a 40 mg/kg dose were 1.6-fold higher in Mdr1a/b(-/-) mice compared to wild-type mice. Plasma concentrations of irinotecan lactone, irinotecan carboxylate, and SN-38 lactone in Mrp4(-/-) mice were similar to the wild-type controls. These results suggest that P-gp plays a role in irinotecan and SN-38 elimination, but Mrp4 does not affect irinotecan or SN-38 plasma pharmacokinetics. PMID- 20583970 TI - Methionine aminopeptidases as potential targets for treatment of gastrointestinal cancers and other tumours. AB - Methionine aminopeptidases (MetAP) are intracellular metalloproteins responsible for the removal of the initiator NH(2)-terminal methionine from newly synthesized proteins, thereby facilitating their intracellular translocation from the ribosome. Two types of MetAP enzymes, MetAP-1 (type-I) and MetAP-2 (type-II), which have a similar three-dimensional structure despite a low homology in their sequences, have been described. Since the discovery that fumagillin, an irreversible MetAP-2 inhibitor, prevents angiogenesis, different studies have been carried out to analyze the role of MetAP proteins as potential targets in cancer treatment. Data obtained indicate that anticancer effect of MetAP-2 inhibitors may be a result of the combined effect of MetAP-2 inhibition in endothelial cells (anti-angiogenesis) and in tumour cells directly. Moreover, it has been recently described that MetAP-1 has a potential role on cell division, and MetAP-1-specific inhibition is able to induce apoptosis in both HeLa and HT 1080 cell lines. A new subtype of MetAP-1, called MetAP-1D, has been found overexpressed in samples from colon cancer patients, its inhibition resulting in a decreased cell growth. Although molecular mechanisms of action of these proteins are largely unknown, a significant progress has been made to understand their structure-function relationships and their physiological roles. Their potential as promising targets in cancer treatment and in the development of new antitumour agents is analyzed focusing on MetAP irreversible inhibitors. The present review summarizes recent research data on different molecules able to induce MetAP inhibition in gastrointestinal cancers and other tumours. PMID- 20583971 TI - Involvement of the toxic AGEs (TAGE)-RAGE system in the pathogenesis of diabetic vascular complications: a novel therapeutic strategy. AB - Diabetic vascular complications are leading causes of acquired blindness, end stage renal failure, a variety of neuropathies, and accelerated atherosclerosis, which may be involved in the disabilities and high mortality rates suffered by diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro inflammatory molecules and elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic vascular complications. Therefore, the inhibition of TAGE formation, blockade of TAGE-RAGE interaction, and the suppression of RAGE expression or its downstream pathways are promising targets for therapeutic interventions against diabetic vascular complications. In this review, we discuss the pathophysiological role of the TAGE-RAGE-oxidative stress system and related therapeutic interventions for preventing the development and progression of diabetic vascular complications. PMID- 20583972 TI - Histone Deacetylase inhibitors: new promise in the treatment of immune and inflammatory diseases. AB - The development of Histone Deacetylase (HDAC) inhibitors has, until recently, principally been driven by their potential as anti-cancer agents. However, there is emerging evidence that HDAC inhibitors could have utility in the treatment of chronic immune and inflammatory disorders, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, airway hyperresponsiveness and organ transplant rejection. Here we discuss the merits of various, structurally-distinct HDAC inhibitors as potential anti-inflammatory therapeutics and provide examples of the novel medicinal chemistry approaches being undertaken to realize HDAC as a druggable target in this clinical setting. PMID- 20583973 TI - Molecular targeting of aberrant transcription factors in leukemia: strategies for RUNX1/ETO. AB - Malignant cell transformation is caused by mutations in distinct key regulatory genes involved in cell growth, apoptosis, senescence and differentiation. Particularly in human leukemia, chromosomal translocations involving crucial hematopoietic transcription factors are frequently causally linked to the disease. Transcription factors commonly have a modular structure, comprising distinct domains for DNA- binding, dimerization and protein-protein interaction. Each domain is functionally important and in principle accessible for a molecular based therapeutic intervention. Uncovering the molecular structure of critical domains will allow the rational development of therapeutic agents that inhibit particular functions of leukemogenic transcription factors. However, so far most approaches are in the experimental stage. Among others, the RUNX1/ETO fusion protein, commonly found within acute myeloid leukemia cells carrying the translocation t(8;21), is currently intensively studied at the functional and structural level as well as in animal models. This combined effort has allowed the development of specific targeting approaches addressing different functional domains of the fusion protein. With a special focus on RUNX1/ETO we will discuss recent strategies to directly interfere with aberrant transcription factors to block their leukemogenic function. PMID- 20583974 TI - Effects of Cissampelos sympodialis Eichl. and its alkaloid, warifteine, in an experimental model of respiratory allergy to Blomia tropicalis. AB - Asthma is one of the most prevalent chronic diseases worldwide. Medicinal plants are historically used in its treatment. The plant Cissampelos sympodialis, known in Northeastern Brazil as "Jarrinha" or "Milona", is used to treat some inflammatory conditions, including asthma. The objective of this study was to evaluate the potential of Cissampelos sympodialis EICHL. extract (CsE) and its isolated alkaloids, especially warifteine (Wa) on a Blomia tropicalis extract (BtE)-induced experimental model of allergy. The respiratory allergy was induced in AJ mice by the administration of BtE. Mice were orally treated with the 400 mg/kg of CsE or 8 mg/kg of total alkaloids fraction (TAF) or 4 mg/kg of Wa and the following parameters were analyzed: (a) total cell numbers in bronchoalveolar fluid (BAF); (b) differential cell numbers in BAF; (c) eosinophil peroxidase (EPO) activity in BAF; (d) IgE serum levels by passive cutaneous anaphylaxis; (e) IL-5, IL-13, IL-10, and IFN-gamma levels in BAF; (f) histopathological alterations in the lung. The treatment of the animals with CsE, Wa or TAF led to a reduction in the numbers of total cells and eosinophils in BAF. The same reduction was observed in EPO levels in the BAF. The levels of IL-5 and IL-13 were also reduced in animals treated with Cissampelos sympodialis, while IL-10 levels were significantly increased in the BAF of CsE-treated animals. The treatment also decreased the density of inflammatory cells in the lung by histopathological examination demonstrating the potential of this medicinal plant as new agent for asthma treatment. PMID- 20583975 TI - Mitigation of radiation injuries via suppression of the renin-angiotensin system: emphasis on radiation nephropathy. AB - Radiation nephropathy and other normal tissue radiation injuries can be successfully mitigated, and also treated, by antagonists of the renin-angiotensin system (RAS). This implies a mechanistic role for that system in radiation nephropathy, yet no evidence exists to date of activation of the RAS by irradiation. RAS antagonists, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are the standard of care in the treatment of subjects with other chronic progressive kidney diseases, in which they exert benefit by reducing both glomerular and tubulo-interstitial injury. These drugs are likely to act in a similar way to mitigate radiation nephropathy. PMID- 20583976 TI - Renin-angiotensin system blockers and modulation of radiation-induced brain injury. AB - Radiation-induced brain injury remains a major cause of morbidity in cancer patients with primary or metastatic brain tumors. Approximately 200,000 individuals/year are treated with fractionated partial or whole-brain irradiation, and > half will survive long enough (<=6 months) to develop radiation-induced brain injury, including cognitive impairment. Although short term treatments have shown efficacy, no long-term treatments or preventive approaches are presently available for modulating radiation-induced brain injury. Based on previous preclinical studies clearly demonstrating that renin angiotensin system (RAS) blockers can modulate radiation-induced late effects in the kidney and lung, we and others hypothesized that RAS blockade would similarly modulate radiation-induced brain injury. Indeed, studies in the last 5 years have shown that both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor antagonists (AT(1)RAs) can prevent/ameliorate radiation induced brain injury, including cognitive impairment, in the rat. The mechanistic basis for this RAS blocker-mediated effect remains the subject of ongoing investigations. Putative mechanisms include, i] blockade of Ang II/NADPH oxidase mediated oxidative stress and neuroinflammation, and ii] a change in the balance of angiotensin (Ang) peptides from the pro-inflammatory and pro-oxidative Ang II to the anti-inflammatory and anti-oxidative Ang-1-7). However, given that both ACEIs and AT(1)RAs are 1] well-tolerated drugs routinely prescribed for hypertension, 2] exhibit some antitumor properties, and 3] can prevent/ameliorate radiation-induced brain injury, they appear to be ideal drugs for future clinical trials, offering the promise of improving the quality of life of brain tumor patients receiving brain irradiation. PMID- 20583978 TI - Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity. AB - The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established radiation injury, for example in the case of radiation accidents or acts of terrorism. PMID- 20583977 TI - Potential targets for intervention in radiation-induced heart disease. AB - Radiotherapy of thoracic and chest wall tumors, if all or part of the heart was included in the radiation field, can lead to radiation-induced heart disease (RIHD), a late and potentially severe side effect. RIHD presents clinically several years after irradiation and manifestations include accelerated atherosclerosis, pericardial and myocardial fibrosis, conduction abnormalities, and injury to cardiac valves. The pathogenesis of RIHD is largely unknown, and a treatment is not available. Hence, ongoing pre-clinical studies aim to elucidate molecular and cellular mechanisms of RIHD. Here, an overview of recent pre clinical studies is given, and based on the results of these studies, potential targets for intervention in RIHD are discussed. PMID- 20583979 TI - Treatment for radiation-induced pulmonary late effects: spoiled for choice or looking in the wrong direction? AB - Due to the radiosensitivity of the lung, toxic endpoints, in the form of radiation pneumonitis and pulmonary fibrosis, are relatively frequent outcomes following radiation treatment of thoracic neoplasms. Because of the potential lethal nature of these normal tissue reactions, they not only lead to quality-of life issues in survivors, but also are deemed dose-limiting and thereby compromise treatment. The mitigation and treatment of lung normal tissue late effects has therefore been the goal of many investigations; however, the complexity of both the organ itself and its response to injury has resulted in little success. Nonetheless, current technology allows us to propose likely targets that are either currently being researched or should be considered in future studies. PMID- 20583980 TI - Hematological targets of radiation damage. AB - Radiation-induced myelosuppression remains a rate-limiting factor of radiotherapy and chemotherapy. Therefore, hematological targets of radiation damage are of great significance for radiation oncology and normal tissue injury and protection. Protection of hematopoietic stem and progenitor cells is pivotal. In order to develop therapeutic targets, it is necessary to understand the mechanisms of stem cell renewal and differentiation. Recent advances in the molecular pathology of hematopoietic stem cells indicate a fine balance between various extrinsic and intrinsic signaling pathways in preserving the self-renewal and proliferative capacity of stem cells. Extrinsic signaling involves a microenvironment niche factors such as neighboring stromal cells, osteoblasts, and adipocytes secreting cytokines, chemokines, and metalloproteinases; intrinsic regulation involves Wnt/hedgehog/Notch signaling, DNA damage-induced epigenetic alterations, telomere shortening, and early senescence. Various drugs including synthetic cytokine mimetics, cytokine stimulators, and DNA repair modulators are being tested as radioprotectants. Colony-stimulating factors are routinely used in clinics to treat neutropenia induced by chemotherapy and radiotherapy as well as to mobilize and expand progenitors used in autologous transplantation. However, toxicity has limited their use. The vitamin E isoforms gamma tocotrienol, a potent free radical scavenger that has displayed promising anticarcinogenic properties, was recently shown to protect bone marrow (BM) from radiation injury and to stimulate hematopoiesis in a murine model. This chapter focuses on the potential targets of radiation damage in BM and speculates on the mechanisms of protection by gamma-tocotrienol and how these mechanisms can contribute to radioprotection in general and to protection of BM during chemotherapy and radiotherapy in particular. PMID- 20583983 TI - Targets of potential radioprotective drugs. PMID- 20583982 TI - Novel strategies to ameliorate radiation injury: a possible role for tetrahydrobiopterin. AB - Novel pharmacological strategies are urgently needed to prevent or reduce radiation-induced tissue injury. Microvascular injury is a prominent feature of both early and delayed radiation injury. Radiation-induced endothelial dysfunction is believed to play a key role in the pathogenesis of post irradiation tissue injury. Hence, strategies that could prevent or improve endothelial malfunction are expected to ameliorate the severity of radiation injury. This review focuses on the therapeutic potential of the nitric oxide synthase (NOS) cofactor 5,6,7,8-tetrahydrobiopterin (BH4) as an agent to reduce radiation toxicity. BH4 is an essential cofactor for all NOS enzymes and a critical determinant of NOS function. Inadequate availability of BH4 leads to uncoupling of the NOS enzyme. In an uncoupled state, NOS produces the highly oxidative radicals superoxide and peroxynitrite at the cost of NO. Under conditions of oxidative stress, such as after radiation exposure, BH4 availability might be reduced due to the rapid oxidation of BH4 to 7,8 dihydrobiopterin (7,8-BH2). As a result, free radical-induced BH4 insufficiency may increase the oxidative burden and hamper NO-dependent endothelial function. Given the growing evidence that BH4 depletion and subsequent endothelial NOS uncoupling play a major role in the pathogenesis of endothelial dysfunction in various diseases, there is substantial reason to believe that improving post irradiation BH4 availability, by either supplementation with it or modulation of its metabolism, might be a novel strategy to reduce radiation-induced endothelial dysfunction and subsequent tissue injury. PMID- 20583984 TI - The renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry. AB - 68Ge/68Ga radionuclide generators have been investigated for almost fifty years now, since the cyclotron-independent availability of positron emitting 68Ga via the 68Ge/68Ga system had always attracted researches working in basic nuclear chemistry as well as radiopharmaceutical chemistry. However, it took decades and generations of research (and researchers) to finally approach a reliable level of 68Ge/68Ga generator designs, adequate to the modern requirements of radiometal labeling chemistry. 68Ga radiopharmacy now is awaking from a sort of hibernation. The exciting perspective for the 68Ge/68Ga generator, now - more than ever, asks for systematic chemical, radiochemical, technological and radiopharmaceutical efforts, to guarantee reliable, highly-efficient and medically approved 68Ge/68Ga generator systems. The expected future broad clinical impact of 68Ga-labelled radiopharmaceuticals - beyond the 68Ga-DOTA-octreotide derivatives - for imaging tumors and many organs, on the other hand, identifies the development of sophisticated Ga(III) chelating structures to be a key factor. Today, open chain complexing agents have almost completely been displaced by macrocyclic DOTA and NOTA-derived conjugates. Structures of chelating moieties are being optimized in terms of thermodynamic stability and kinetic inertness, in terms of labeling efficacies at different, even acidic pH, and in terms of synthetic options towards bifunctionality, directed to sophisticated covalent coupling strategies to a variety of biologically relevant targeting vectors. Today, one may expect that the 68Ge/68Ga radionuclide generator systems could contribute to and facilitate the clinical impact of nuclear medicine diagnoses for PET in a dimension comparable to the established 99Mo/99(m)Tc generator system for SPECT. PMID- 20583985 TI - Radioligands for the PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5). AB - Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCR), which activate intracellular secondary messenger systems when bound by the physiological ligand glutamate. Modulation of mGluR5s has potential for the treatment of variety of psychiatric and neurological diseases such as depression, anxiety, schizophrenia and Parkinson's disease. Positron emission tomography (PET) might offer the possibility to visualize the mGluR5 and present an interesting tool for studying this receptor-subtype under physiologic and pathologic conditions. In this review paper, emphasis is given to the radiosynthesis, in vitro and in vivo characterization of recently published mGluR5 PET tracers. PMID- 20583981 TI - Modifying radiation damage. AB - Radiation leaves a fairly characteristic footprint in biological materials, but this is rapidly all but obliterated by the canonical biological responses to the radiation damage. The innate immune recognition systems that sense "danger" through direct radiation damage and through associated collateral damage set in motion a chain of events that, in a tissue compromised by radiation, often unwittingly result in oscillating waves of molecular and cellular responses as tissues attempt to heal. Understanding "nature's whispers" that inform on these processes will lead to novel forms of intervention targeted more precisely towards modifying them in an appropriate and timely fashion so as to improve the healing process and prevent or mitigate the development of acute and late effects of normal tissue radiation damage, whether it be accidental, as a result of a terrorist incident, or of therapeutic treatment of cancer. Here we attempt to discuss some of the non-free radical scavenging mechanisms that modify radiation responses and comment on where we see them within a conceptual framework of an evolving radiation-induced lesion. PMID- 20583986 TI - Radioligands for the angiotensin II subtype 1 (AT1) receptor. AB - Over the last years, ligands for angiotensin II subtype 1 receptor (AT1R) have been developed as an alternative to the use of angiotensin-converting enzyme (ACE) inhibitors for controlling high blood pressure. Radiolabeled versions of these ligands have proven vital to the development of more potent and specific drugs for the treatment of hypertension. Imaging studies using radiolabeled AT1R ligands have also elucidated the role these receptors play in angiogenesis as well as in various disease states beyond hypertension. PMID- 20583987 TI - Current state of agonist radioligands for imaging of brain dopamine D2/D3 receptors in vivo with positron emission tomography. AB - Dopamine (DA) is known to play an important role in numerous brain functions and has been suggested to be involved in several neuropsychiatric and neurological disorders. From early on, positron emission tomography (PET) studies of the DA system have yielded high interest. Currently, several aspects of the functionality of DA neurons can be imaged, including the DA synthesis rate and the expression of DA-related proteins (receptors and transporters). A more recent application of radioligands targeting DA receptors is to study the endogenous neurotransmitter levels in vivo in brain. In vitro binding studies have suggested that in general DA receptors, as many other G-protein coupled receptors, exist in two affinity states for agonist binding. The high affinity state is thought to represent the functional state of the receptor, and the proportion between high and low affinity states may change with the development of disease. PET imaging with agonist radioligands may provide information on the existence of the high affinity state in vivo. In addition, DA receptor agonist radioligands may be superior tools for measuring changes in endogenous DA levels as antagonist radioligands inherently bind to both the low and the high affinity state. This review primarily summarizes the present status of the D(2)/D(3) receptor agonist PET radioligands. In addition several PET studies evaluating the utility of the agonist concept are discussed. PMID- 20583988 TI - Radionuclide based imaging of prostate cancer. AB - Prostate cancer (PCa) is the second leading cause of cancer deaths in American men. Early detection of PCa by blood tests for elevated levels of prostate specific-antigen (PSA) has lead to early treatment and a reduction in death rates. However, PSA level alone does not distinguish between PCa and normal conditions that cause elevated PSA. Furthermore, because PCa can be a very slow growing cancer, even confirmation of PCa cells in a biopsy gives no indication whether the PCa will progress into active disease within the individual's lifetime. As a result many patients receive treatment that they may not need. Imaging is an attractive modality for the detection and characterization of disease because most techniques are non- or minimally invasive, nondestructive, provide dynamic real-time data, and allow for repeat measurements. In PCa, advanced imaging techniques could be useful for accurate staging of primary disease, restaging of recurrent disease, detection of metastatic lesions, and predicting the aggressiveness of the disease. This paper reviews the radionuclide based imaging agents for planar, single photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging currently used in the clinic and those under development for PCa. The former includes the bone agents technetium diphosphonates and F-18 fluoride, the metabolic agents 2-[18F]fluoro-2 deoxy-D-glucose (FDG), and receptor targeted radiolabeled monoclonal antibodies including ProstaScint. The latter agents include C-11 acetate, C-11 and F-18 choline, C-11 and F-18 labeled 1-aminocyclobutane-1-carboxylic acid, radiolabeled androgen receptor binding compounds, radiolabeled peptides and small molecules for receptors over expressed either on prostate cancer itself or on the associated tumor neovasculature. Coregistration of PET or SPECT images with CT or MRI scans, improvements in imaging cameras, and image reconstruction algorithms have improved the quality of the images to the point where dual modality (radionuclide/CT or MRI) imaging with several agents can now be considered for staging of PCa. In addition, the high selectivity and rapid localization of many of the new agents under development portends promise for a greater use of radionuclide imaging for prostate cancer detection, characterization, and treatment monitoring. PMID- 20583989 TI - [11C]Phosgene: a versatile reagent for radioactive carbonyl insertion into medicinal radiotracers for positron emission tomography. AB - [11C]Phosgene has been playing a relatively modest but continuous and manifest role all along the history of radiochemistry for Positron Emission Tomography. It acts as a radiolabelling agent through carbonyl insertion, usually between heteroatoms, and benefits from a high chemical reactivity allowing for short reaction times. The aim of this review is to give an overview of this radiochemistry from its beginning until the present day. After drawing up the inventory of the various ways of its production, the reactions in which it has been employed and the labelled products that have been synthesised with it are catalogued. This comprises the reactions of [11C]phosgene with primary, secondary and tertiary amines to labelled isocyanates and carbamoyl chlorides, which serve as intermediates for symmetrical and unsymmetrical [11C]ureas and [11C]carbamates, reactions with alcohols leading to labelled carbamates and carbonates via [11C]chloroformates, cyclisation reactions to heterocycles and the radiochemistry of the secondary radiolabelling agents [11C]urea and diethyl- or dimethyl [11C]carbonate. Apart from this already vast field of chemical possibilities there should be room for extension of the use of [11C]phosgene to other chemistry, notably that of C-11C bond formation. PMID- 20583990 TI - PET radioligands for the vesicular acetylcholine transporter (VAChT). AB - The vesicular acetylcholine transporter (VAChT) is a glycoprotein responsible for the accumulation of acetylcholine into pre-synaptic vesicules of cholinergic neurons. Cholinergic innervation has been shown to be decreased at the earlier stages of Alzheimer's disease (AD). Thus, the expression of VAChT has been correlated with the severity of the dementia and has been considered as a significant diagnostic target for AD. To this end numerous radioligands based on the vesamicol scaffold have been developed for imaging the VAChT using positron emission tomography (PET). Among the various radioligands only a small number have been evaluated in vivo in non-human primate and human. Despite promising in vitro, ex vivo and first in vivo studies, most of them are unsuitable for clinical use in humans due to poor selectivity over sigma receptors, low extraction from the blood, slow brain kinetics or fast metabolism. To date (-) [(11)C]OMV (1), (-)-[(11)C]MABV (2), (-)-[(18)F]-FEOBV (6), (-)-trans-2-hydroxy-3 (4-(4-[(18)F]fluorobenzoyl)piperidine)tetralin (8) and [(18)F]FBMV (12) are promising radioligands for the VAChT, though further validation is required to confirm their clinical usefulness. PMID- 20583991 TI - Labeling strategies of peptides with 18F for positron emission tomography. AB - A variety of peptides labeled with the positron emitting radionuclide fluorine-18 have shown promise as tracers for use in positron emission tomography (PET) for the detection of malignancies. Peptides can be produced with a formidable versatility allowing them to target a vast diversity of uniquely expressed or overexpressed receptors associated with pathological conditions. The quantitative nature of PET gives the opportunity to stage and monitor the progress of the disease. The pharmacokinetics of peptides are compatible with the half-life of fluorine-18 (110 min), allowing the generation of high quality PET images within the time frame of 1-3 hours or longer. The production of high energy gamma emitting radiopharmaceuticals puts certain constraints and requirements on the production method. These are to a large extent dictated by the short half-life of the 18F and the need for appropriate shielding of the operator. For large scale productions, a fully automated production process is a requirement. Compared to low molecular weight fluorine-18 labeled tracers, the production of 18F-labeled peptides entails specific challenges. As opposed to small organic molecules where direct labeling with no-carrier added 18-fluoride is feasible, peptides do not normally allow for such a direct labeling approach. Therefore, peptides are for all practical purposes labeled by 18F-prosthetic groups, also called bifunctional labeling agents, making their synthesis relatively complicated. During the last decade, various methodologies have been developed for the introduction of 18F fluoride into peptides. The strategies employed for the labeling of peptides with 18F all represent their own advantages and inconveniences, still some are more flexible than others. In this review, the aim is to provide an overview and discuss the strategies currently used for labeling of peptides with 18F for PET. PMID- 20583992 TI - Recent development of radioligands for imaging alpha7 nicotinic acetylcholine receptors in the brain. AB - The alpha7 nicotinic acetylcholine receptors (nAChRs), ligand-gated Ca(2+) channels composed of homopentamers of alpha7 subunits, represent the most abundant with alpha4beta2 nAChRs in the brain. Several lines of evidence suggest that alpha7 nAChRs play a role in the physiology of neuropsychiatric diseases such as schizophrenia, Alzheimer's disease, anxiety, depression, and drug addiction; hence, alpha7 nAChRs seem to be attractive therapeutic targets for these diseases. Several researchers have attempted to develop radioligands that can be used to selectively and quantitatively examine the distribution of alpha7 nAChRs in the human brain with positron emission tomography (PET) or single photon emission tomography (SPECT). Although efforts are underway, very low density of alpha7 nAChR and scarcity of very high affinity ligands hamper the development of alpha7 subtype-selective radioligands for in vivo imaging. In this article, we review the recent topics on the development of PET/SPECT ligands for in vivo imaging of alpha7 nAChRs in the brain. PMID- 20583993 TI - Radiolabeled nucleoside analogues for PET imaging of HSV1-tk gene expression. AB - The HSV1-tk gene has been explored as a reporter and/or suicide gene in molecular imaging of gene expression. Gene therapy with HSV1-tk and the use of this gene as a marker have been applied in patients with various forms of cancer. However, the conditions for clinical gene therapy protocols have yet to be optimized. A method to monitor the activity of HSV-tk in vivo would be extremely useful to optimize clinical gene therapy protocols. Positron emission tomography (PET) with a suitable probe can offer information about both the extent of gene expression and its distribution, provided that an appropriate reporter gene is included in the therapeutic cassette. PET imaging provides higher resolution and sensitivity and allows noninvasive quantification of biological processes. Several radiolabeled pyrimidine (thymidine) and purine (acycloguanosine) derivatives have been developed as reporter probes for imaging of HSV-TK enzyme activity with PET. In this review, information on radiolabeling and PET imaging of HSV1-tk gene expression with various nucleoside analogues is presented. PMID- 20583994 TI - Non-invasive imaging of the type 2 cannabinoid receptor, focus on positron emission tomography. AB - The type 2 cannabinoid receptor (CB(2)R) is a relatively new target for drug development, as the receptor was only discovered in 1993. The CB(2)R is mainly expressed in tissues and organs related to the immune system. However, in pathological conditions, mostly inflammatory, a strong upregulation has been observed. Because of its expression in activated microglia, the type 2 cannabinoid receptor might play an important role in pathologies with a neuroinflammatory component. Positron emission tomography provides a sensitive non-invasive imaging technique to study and quantify receptor expression. In this review, the importance of CB(2)R imaging, the current status and the future possibilities for the development of CB(2)R PET radioligands are discussed. PMID- 20583995 TI - Development of effective PET and SPECT imaging agents for the serotonin transporter: has a twenty-year journey reached its destination? AB - The serotonin transporter (SERT) has been implicated in a variety of neuropsychiatric disorders including depression, schizophrenia, substance abuse, alcoholism, and Alzheimer's disease. Radiotracer-based in vivo imaging techniques such as Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) are important tools to investigate the functions of SERT in the living brain under normal conditions and its dysfunction in diseases. In this report we review the development and validation of effective PET and SPECT radiotracers in the last twenty years. First, the requirements for an effective imaging tracer, and factors influencing a tracer's in vivo imaging performance are discussed. PET and SPECT radiotracers for SERT are then categorized and reviewed according to their chemical scaffolds: 1) SSRIs and related compounds; 2) tropane-based ligands; 3) isoquinolines; and 4) substituted diarylsulfides. Critical evaluation and comments are provided for promising radiotracers, if any, emerging from each chemical scaffold. Based on experimental data gathered from radiotracer development for SERT, an examination of the relationship between an imaging tracer's in vitro physicochemical and pharmacological properties and its in vivo performance parameters is provided. Finally, tracers available for imaging applications in humans are assessed and compared in terms of tissue binding kinetics, non-specific binding, and specific binding signals in vivo. From these assessments, we conclude that, after twenty years of development efforts, a number of effective PET and SPECT radiotracers have now been validated and are available for imaging SERT in humans. The applications of these efficacious SERT imaging agents will further advance our understanding of this important transporter in psychiatric and neurodegenerative disorders. PMID- 20583996 TI - Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors. AB - MSC (mesenchymal stromal cells) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. In the present study, we investigated whether MSC have protective/reparative effects in anti-Thy1 disease, an Ab (antibody)-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats: (i) rats injected with anti-Thy1.1 Ab on day 0 (group A); (ii) rats injected with anti-Thy1.1 Ab on day 0+MSC on day 3 (group B); (iii) rats injected with anti-Thy1.1 Ab on day 0+mesangial cells on day 3 (group C); (iv) rats injected with saline on day 0+MSC on day 3 (group D); and (v) rats injected with saline on day 0 (group E). Rats were killed on days 1, 3, 7 and 14. MSC prevented the increase in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, MSC suppressed the release of IL-6 (interleukin-6) and TGF-beta (transforming growth factor-beta), modulated glomerular PDGF-beta (platelet-derived growth factor-beta), and reset the scatter factors and their receptors, potentiating HGF (hepatocyte growth factor)/Met and inactivating MSP (macrophage-stimulating protein)/Ron (receptor origin nantaise). Few MSC were found in the kidney. These results indicate that MSC improve anti-Thy 1 disease not by replacing injured cells, but by preventing cytokine-driven inflammation and modulating PDGF-beta and the scatter factors, i.e. systems that regulate movement and proliferation of monocytes and mesangial cells. PMID- 20583997 TI - PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. AB - The beta-isoform of PIP4K (PtdIns5P-4-kinase) regulates the levels of nuclear PtdIns5P, which in turn modulates the acetylation of the tumour suppressor p53. The crystal structure of PIP4Kbeta demonstrated that it can form a homodimer with the two subunits arranged in opposite orientations. Using MS, isoform-specific antibodies against PIP4Ks, RNAi (RNA interference) suppression and overexpression studies, we show that PIP4Kbeta interacts in vitro and in vivo with the PIP4Kalpha isoform. As the two isoforms phosphorylate the same substrate to generate the same product, the interaction could be considered to be functionally redundant. However, contrary to expectation, we find that PIP4Kbeta has 2000-fold less activity towards PtdIns5P compared with PIP4Kalpha, and that the majority of PIP4K activity associated with PIP4Kbeta comes from its interaction with PIP4Kalpha. Furthermore, PIP4Kbeta can modulate the nuclear localization of PIP4Kalpha, and PIP4Kalpha has a role in regulating PIP4Kbeta functions. The results of the present study suggest a rationale for the functional interaction between PIP4Kalpha and PIP4Kbeta and provide insight into how the relative levels of the two enzymes may be important in their physiological and pathological roles. PMID- 20583998 TI - Promiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa. AB - The MexAB-OprM drug efflux pump is central to multidrug resistance of Pseudomonas aeruginosa. The ability of the tripartite protein to confer drug resistance on the pathogen is crucially dependent on the presence of all three proteins of the complex. However, the role of each protein in the formation of the intact functional complex is not well understood. One of the key questions relates to the (in)ability of MexB to act independently of its cognitive partners, MexA and OprM. In the present study, we have demonstrated that, in the absence of MexA and OprM, MexB can: (i) recruit AcrA and TolC from Escherichia coli to form a functional drug-efflux complex; (ii) transport the toxic compound ethidium bromide in a Gram-positive organism where the periplasmic space and outer membrane are absent; and (iii) catalyse transmembrane chemical proton gradient (DeltapH)-dependent drug transport when purified and reconstituted into proteoliposomes. Our results represent the first evidence of drug transport by an isolated RND (resistance-nodulation-cell division)-type multidrug transporter, and provide a basis for further studies into the energetics of RND-type transporters and their assembly into multiprotein complexes. PMID- 20583999 TI - Epithelial marker expression in Salzmann nodular degeneration shows characteristics of limbal transient amplifying cells and alludes to an involvement of the epithelium in its pathogenesis. AB - PURPOSE: To look at the epithelial nature of Salzmann nodular degeneration (SND) and its possible relation with the aetiology of the subepithelial collagen deposition. METHODS: Histological slides of 28 patients with SND were analysed for limbal and central corneal epithelial markers. Expression pattern of these markers in the basal layer of the epithelium was analysed and compared to the expression pattern in central corneal and limbal epithelium. Statistical analysis was performed by means of analysis of variance. RESULTS: Expression of the epithelial stem cell marker ABCG2 and p63 was low in SND. Expression of CK12, a marker for terminally differentiated epithelium, was low, as well. But, CK19 and Enolase-alpha expressions were significantly increased and resembled the expression pattern of transient amplifying cells (TAC) of the limbus. CONCLUSION: The epithelium in SND shows similar characteristics as TAC of the limbus and seems to be metabolically more active than the differentiated central corneal epithelium. This could be related to the deposition of subepithelial collagen fibrils seen in SND and points out a possible involvement of the corneal epithelium in the aetiology of Salzmann nodular degeneration. PMID- 20584000 TI - The eye of Vesalius. AB - In the time of Vesalius, knowledge of ocular anatomy was limited. The first description of the anatomy of the eye comes from Democrites, for whom the eye was surrounded by two 'coats', filled with a homogenous fluid. The optic nerve was hollow and the lens was considered to be a postmortem artefact. Until the 15th century AD, medicine was influenced by the writings of Galenus and the model of the eye he proposed was still considered valid, even after Vesalius. According to the Alexandrian tradition, the lens was considered as the seat of visual perception. Although Vesalius rightly deserves the title of father of modern anatomy, his description of ocular anatomy was rudimentary and often incorrect. He described a musculus retractorius bulbi, which is found only in lower mammals, not in primates. The lens, the role of which as an optical device he recognized correctly, was placed too centrally in the eye. The optic nerve was not correctly placed and, following Galenus, Vesalius described only seven cranial nerves. The Galenian concept of ocular anatomy was to endure until the development of the microscope by Anthony van Leeuwenhoek. Modern ocular anatomy, in fact, can be dated from the works of Zinn. PMID- 20584001 TI - Neutrophil-dominant experimental autoimmune uveitis in CC-chemokine receptor 2 knockout mice. AB - PURPOSE: Murine experimental autoimmune uveitis (EAU) is an animal model of human uveitis. It has been demonstrated that ocular-infiltrating macrophages are crucial for EAU induction, and monocyte chemoattractant protein-1 (MCP-1) was actually upregulated in the eye. CC chemokine receptor-2 (CCR2) is the receptor of MCP-1, and macrophages fail to recruit particular lesions in CCR2 knockout (KO) mice. To confirm the role of macrophages in EAU, we examined EAU in CCR2 KO mice. METHODS: CCR2 KO mice and wild-type (WT) mice that had the same genetic background were immunized with human interphotoreceptor retinoid-binding protein peptide 1-20 emulsified in complete Freund's adjuvant. At multiple time-points, EAU severity was evaluated based on microscopic fundus observation and histological examination. To examine the phenotype of retinal-infiltrating cells, single cells were prepared from the eye and analysed by flow cytometry. RESULTS: In WT mice, EAU was induced at the peak of day 16 and marked macrophage infiltration was observed. Although macrophages failed to be recruited into the eye in CCR2 KO mice, severe uveitis was induced unexpectedly. Flow cytometry and histology revealed that most of the infiltrating cells were neutrophils. We also compared the intraocular chemokine concentrations between WT mice and KO mice. Two CXC chemokine (monokine induced by interferon-gamma and interferon-gamma inducible protein-10) were upregulated in KO mice. CONCLUSION: Interphotoreceptor retinoid-binding protein peptide immunization caused neutrophil-dominant uveitis in CCR2 KO mice. In the absence of macrophages, neutrophils can be alternatively recruited and can cause tissue damage. PMID- 20584002 TI - Intravitreal ranibizumab treatment of retinal angiomatous proliferation. AB - PURPOSE: To determine the efficacy of intravitreal injections of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) in neovascular age related macular degeneration. METHODS: Retrospective, consecutive case series of 26 eyes (26 patients) treated with intravitreal injections of 0.5 mg ranibizumab for RAP. Patients received intravitreal injections at monthly intervals during upload phase for a 3-month period. RESULTS: Mean visual acuity before treatment was 0.75 +/- 0.38logMAR (mean +/- SD, n = 26). In the upload phase, mean visual acuity improved 4 weeks after the initial injection to 0.6 +/- 0.37logMAR (n = 26) and to 0.53 +/- 0.34logMAR (n = 26) 4 weeks after the third monthly intravitreal injection of ranibizumab. The mean optical coherence tomography (OCT) central foveal thickness reduced from 345 +/- 55 MUm at baseline to 215 +/- 87 MUm at 3 months. In the maintenance phase, mean visual acuity after 6 months was 0.66 +/- 0.38logMAR (n = 12) and 0.7 +/- 0.37logMAR after 9 months (n = 6). The mean OCT central foveal thickness was 259 +/- 59 MUm (n = 13) at 6 months and 280 +/- 127 MUm (n = 6) at nine-month follow-up. CONCLUSION: Intravitreal ranibizumab resulted in an improvement of visual acuity 4 weeks after the first injection but was more pronounced after 3 months. A reduction in leakage and OCT central foveal thickness was seen 3 months after the commencement of treatment. PMID- 20584003 TI - Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. AB - BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. OBJECTIVES: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. RESULTS: None of the 2496 reports identified satisfied the inclusion criteria. CONCLUSIONS: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose. PMID- 20584004 TI - Allergen cross reactions: a problem greater than ever thought? AB - BACKGROUND: Cross reactions are an often observed phenomenon in patients with allergy. Sensitization against some allergens may cause reactions against other seemingly unrelated allergens. Today, cross reactions are being investigated on a per-case basis, analyzing blood serum specific IgE (sIgE) levels and clinical features of patients suffering from cross reactions. In this study, we evaluated the level of sIgE compared to patients' total IgE assuming epitope specificity is a consequence of sequence similarity. METHODS: Our objective was to evaluate our recently published model of molecular sequence similarities underlying cross reactivity using serum-derived data from IgE determinations of standard laboratory tests. We calculated the probabilities of protein cross reactivity based on conserved sequence motifs and compared these in silico predictions to a database consisting of 5362 sera with sIgE determinations. RESULTS: Cumulating sIgE values of a patient resulted in a median of 25-30% total IgE. Comparing motif cross reactivity predictions to sIgE levels showed that on average three times fewer motifs than extracts were recognized in a given serum (correlation coefficient: 0.967). Extracts belonging to the same motif group co-reacted in a high percentage of sera (up to 80% for some motifs). CONCLUSIONS: Cumulated sIgE levels are exaggerated because of a high level of observed cross reactions. Thus, not only bioinformatic prediction of allergenic motifs, but also serological routine testing of allergic patients implies that the immune system may recognize only a small number of allergenic structures. PMID- 20584005 TI - Management of anaphylaxis in primary care: Canadian expert consensus recommendations. AB - BACKGROUND: Anaphylaxis is often managed inadequately. We used findings from a systematic review of gaps in anaphylaxis management to develop evidence-based recommendations for gaps rated as clinically important by a panel of Canadian allergy experts. METHODS: The nominal group technique (NGT) consensus methodology was used to develop evidence-based recommendations for the management of anaphylaxis in primary care. Physician-specific gaps from our systematic review were prioritized by consensus meeting participants in two rounds, which involved the rating, discussion, and re-rating of gaps. Using current anaphylaxis guidelines, recommendations were then developed for each category of gaps that were identified by the panel as clinically important. RESULTS: Thirty unique physician gaps from the systematic review were categorized according to gaps of knowledge and anaphylaxis practice behaviors. The panel rated diagnosis of anaphylaxis, and when and how to use epinephrine auto-injectors as clinically important knowledge gaps; and rated infrequent or delayed epinephrine administration, low rate of auto-injector prescription, and infrequent or no referrals to allergy specialists after a reaction as important practice behavior gaps. Evidence from four guidelines was used to support the consensus recommendation statements for three resulting categories of gap themes: anaphylaxis management, epinephrine use, and follow-up care. CONCLUSION: We used an NGT consensus methodology to develop an educational resource for primary care physicians and allergists to better understand how to manage patients with anaphylaxis. Next steps include testing our findings against observed data in primary care settings and to develop other strategies or tools to overcome gaps in anaphylaxis management. PMID- 20584006 TI - Occupational allergy to bell pepper pollen in greenhouses in the Netherlands, an 8-year follow-up study. AB - BACKGROUND: Pollen from bell pepper plants cultivated in greenhouses are known to cause occupational allergic disease. A cross-sectional study among 472 bell pepper employees in 1999 estimated prevalences for sensitization to bell pepper pollen of 28% and for work-related allergic symptoms of 54%. There is scarce information on the incidence of work-related allergy and its risk factors. Aims of the present study were to estimate the cumulative incidence of work-related symptoms and sensitization to bell pepper pollen, and to determine risk factors for the onset of these symptoms and sensitization. METHODS: Bell pepper employees who participated in a cross-sectional survey in 1999 were asked to take part in a follow-up study in 2007. Information on demographic characteristics, job characteristics and allergic symptoms was gathered by means of a questionnaire. Furthermore, skin tests were performed with a.o. bell pepper pollen. RESULTS: In total, 280 of 472 employees were available for questionnaires and in 250 employees allergy tests were performed. During the 8-year follow-up, the cumulative incidence of sensitization to bell pepper pollen was 9% and of work related rhinitis 19%. Atopy [odds ratio (OR) 5.60] and smoking (OR 3.53) were significantly associated with development of rhinitis. The cumulative incidence of work-related asthma symptoms was 8%. Again atopy (OR 5.03) and smoking (OR 11.85) were significant risk factors. CONCLUSION: Cumulative incidences for sensitization to bell pepper pollen, work-related rhinitis and asthma symptoms were 9%, 19% and 8%, respectively. Atopy and smoking are risk factors for developing work-related symptoms among workers in bell pepper horticulture. PMID- 20584007 TI - Discrimination between moderate and severe disease may be used in patients with either treated or untreated allergic rhinitis. AB - BACKGROUND: Allergic rhinitis (AR) is a common disease with major socioeconomic burden and a significant impact on quality of life. OBJECTIVE: The aim of this study was to discriminate between moderate and severe AR patients whether receiving treatment or not, using a modified criterion of allergic rhinitis and its impact on asthma (ARIA) classification. METHODS: The modified ARIA severity classification (J Allergy Clin Immunol, 120, 2007, 359) categorizes AR as mild (no items affected), moderate (1-3 items affected), and severe (all four items affected). We applied these criteria to 1666 treated and 1058 untreated AR patients and compared their symptoms total four-symptom score (T4SS) and quality of life (ESPRINT-15), according to their clinical severity. RESULTS: Allergic rhinitis clinical status was significantly worse (P < 0.001) in treated than in untreated patients. For both treated and untreated patients, T4SS and ESPRINT-15 Quality of life scores were significantly worse (P < 0.001) in severe than in moderate patients. CONCLUSIONS: The modified ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among both treated and untreated patients. PMID- 20584008 TI - Early markers for protective mechanisms during rush venom immunotherapy. AB - BACKGROUND: Allergen-specific venom immunotherapy (VIT) represents the only rational-based option to treat allergic sensitizations against bee and wasp venom. So far, there is not much knowledge about early induction of protective and tolerogenic pathways during VIT. OBJECTIVES: To identify the earliest markers for protective mechanisms against allergic reactions in the peripheral blood during the build-up phase of VIT. METHODS: PBMC and monocytes were isolated, and serum samples were taken before and during a five day build-up phase from 65 hymenoptera venom allergic patients. Expression level of tolerogenic markers was analyzed on mRNA and protein level. Serum levels of different soluble tolerogenic factors were measured. RESULTS: We observed significantly enhanced tryptophan degradation, elevated ILT4 expression of monocytes as well as IL-10 production of CD3(+) T cells only a few hours after the first injection on day 1, followed by increased IL-10 serum levels, monocyte apoptosis and elevated intracellular cAMP levels of monocytes on day 3 combined with a higher ILT3 protein expression and IL-10 secretion of monocytes on day 5. CONCLUSION: From these data, we conclude that tryptophan depletion, ILT3/4-mediated inhibition, higher IL-10 production as well as intracellular cAMP might contribute to early induction of protective mechanisms against allergic reactions during the build-up phase of VIT. PMID- 20584009 TI - Lymphocytes in endometriosis. AB - Endometriosis is a disease characterized by the presence of endometriotic tissue outside the uterine cavity. Although its pathogenesis remains to be elucidated, immune status is suggested to play an important role in the initiation and the progression of the disease. In particular, immune cells in lymphoid lineage that comprised T and B lymphocytes and natural killer cells play essential roles in determining either accept or reject survival, implantation, and proliferation of endometrial and endometriotic cells. Numerous studies have shown aberrant functions of these immune cells in women with endometriosis. The abnormalities include reduced activity of cytotoxic T cells and NK cells, cytokine secretion by helper T cells, and autoantibody production by B lymphocytes. These alterations are suggested to be induced by various manners and promote the disease. Understanding of these immune aspects in endometriosis is thus expected to benefit the treatment of the disease. PMID- 20584010 TI - The myxovirus resistance protein, MX1, interacts with tubulin beta in uterine glandular epithelial cells. AB - PROBLEM: MX proteins are upregulated during viral infection and during early pregnancy in ruminants by type I interferons and exhibit a number of characteristics that would suggest they function in basic cellular processes. We hypothesize MX1 plays a role in intracellular trafficking and secretion, and the objective of this study was to identify cellular proteins that interact with MX1. METHOD OF STUDY: western blot and polymerase chain reaction were used to detect expression of MX1 and endogenous interferon (IFN), respectively. Affinity chromatography and mass spectrometry identified proteins that interacted with MX1. These interactions were confirmed and characterized using co immunoprecipitation and co-immunofluorescence. RESULTS: MX1 was expressed in ovine glandular epithelial cells without IFN treatment, while another interferon stimulated gene, ISG15, was not. MX1 was shown to interact with tubulin beta (TUBB) during interphase and mitosis and nocodazole disrupted this interaction. CONCLUSION: we propose that by tethering to TUBB, MX1 could be transporting proteins or vesicles throughout the cell, such as those destined for secretion or required for mitosis. This would be a novel role for an ISG, but one that is consistent with the enhanced secretion occurring in the uterus during early pregnancy in ruminants in response to conceptus-produced IFN-tau. PMID- 20584011 TI - Incidence of sperm-immobilizing antibodies in infertile women with past Chlamydia trachomatis infection. AB - PROBLEM: Among the risk factors for antisperm antibody production, inflammatory diseases of the genital tract are believed to play an important role. Chlamydia trachomatis infection is one of the most common sexually transmitted diseases. There are some reports suggesting that human sperm have antigens that cross-react immunologically with certain microbial antigens, such as C. trachomatis. However, this is still controversial. We performed a retrospective study to investigate the correlation between anti-chlamydial antibodies and sperm-immobilizing antibodies in infertile women. METHOD OF STUDY: Between January 2007 and March 2009, the presence of sperm-immobilizing antibodies was examined by the sperm immobilization test using sera from 273 infertile women. Anti-chlamydial antibodies (IgG and IgA) were examined to prove past C. trachomatis infection by ELISA using the same sera from infertile women. RESULTS: The overall incidence of sperm-immobilizing antibodies was 2.9% (8/273) in infertile women. The incidences of sperm-immobilizing antibodies were 6.4% (5/78) in cases with past C. trachomatis infection and 1.5% (3/195) in cases without past C. trachomatis infection. There was a significant difference between the two groups (P = 0.031). CONCLUSION: A significantly higher incidence of sperm-immobilizing antibodies was noted in infertile women with past C. trachomatis infection compared with that of those without past C. trachomatis infection. This is the first demonstration that C. trachomatis infection could play a role in the production of sperm immobilizing antibodies in infertile women. PMID- 20584013 TI - Indoleamine 2,3-dioxygenase gene in pre-eclampsia. PMID- 20584015 TI - Intra-arterial chemotherapy for retinoblastoma: the beginning of a long journey. AB - Conservative management of retinoblastoma has evolved from external beam radiotherapy to systemic chemotherapy by intravenous route and now to localized chemotherapy by intra-arterial route in some cases. With 16-year experience, systemic chemotherapy has been found effective for minimal to moderately advanced retinoblastoma with tumour control of 90% or better, few side effects and even hope for return of some vision. Localized intra-arterial chemotherapy with delivery under fluoroscopy and catheterization of the ophthalmic artery is now undergoing evaluation and appears to provide striking control for retinoblastoma, particularly recurrent tumour seeds following other therapies. The limitations and complications of this approach have yet to be defined. Toxicity of the chemotherapy to the delicate retinal vessels is unknown. Despite its allure, intra-arterial chemotherapy should be used with caution, as in other fields of paediatric oncology it has been found to provide no advantage over intravenous chemotherapy. Time will tell. PMID- 20584014 TI - Enlarging the scope of cell-penetrating prenylated peptides to include farnesylated 'CAAX' box sequences and diverse cell types. AB - Protein prenylation is a posttranslational modification that is present in a large number of proteins; it has been proposed to be responsible for membrane association and protein-protein interactions, which contribute to its role in signal transduction pathways. Research has been aimed at inhibiting prenylation with farnesyltransferase inhibitors based on the finding that the farnesylated protein Ras is implicated in 30% of human cancers. Despite numerous studies on the enzymology of prenylation in vitro, many questions remain about the process of prenylation as it occurs in living cells. Here we describe the preparation of a series of farnesylated peptides that contain sequences recognized by protein farnesyltransferase. Using a combination of flow cytometry and confocal microscopy, we show that these peptides enter a variety of different cell types. A related peptide where the farnesyl group has been replaced by a disulfide linked decyl group is also shown to be able to efficiently enter cells. These results highlight the applicability of these peptides as a platform for further study of protein prenylation and subsequent processing in live cells. PMID- 20584016 TI - Hospital-admitted eye injury in Victoria, Australia. AB - BACKGROUND: The public health concern represented by eye injury in Victoria, Australia has been known for a period now approaching 20 years. However, there has been no improvement observed in this public health concern since it was first identified in the 1990s. This study further investigates the epidemiology of eye injury in Victoria, specifically hospital-admitted eye injury. METHODS: The Victorian Admitted Episodes Dataset was surveyed for eye injury coded by the International Classification of Diseases 10th revision during the period spanning 2001-2005, retrieving all cases of hospital-admitted eye injury in Victoria during the surveyed period. RESULTS: During the period surveyed, the average incidence of eye injury requiring hospital admission in Victoria was 53.6 per 100 000 person-years. Sixty-four per cent of patients were male and 36% were female (P < 0.001). Male patients were most commonly middle-aged compared with female patients who were most commonly middle-aged to elderly (P < 0.001). Core patient groups included: elderly women sustaining eye injuries as a result of falls (particularly in residential homes); middle-aged men sustaining eye injuries as a result of assault and in transport-related accidents. CONCLUSION: The incidence of hospital-admitted eye injury in Victoria has increased since it was first identified as a concern in the 1990s. The design and implementation of an effective preventative strategy to reduce the rate of hospital-admitted eye injury in Victoria presents as a difficult task given that the most common causes are represented by falls, assault and transport-related accidents. PMID- 20584017 TI - Demographic characteristics, patterns and risk factors for retinal vein occlusion in Nepal: a hospital-based case-control study. AB - PURPOSE: Retinal vein occlusion (RVO) is an increasing problem leading to visual impairment in Nepal. Our study investigates the demographic characteristics, patterns and risk factors for RVO in this developing Asian country. METHODS: This is a hospital-based case-control study conducted at the Tilganga Institute of Ophthalmology of Nepal during the period of January 2007 to January 2008. All consecutive new cases of RVO diagnosed at the Institute were included. Cases with intraocular inflammation or a prior history of intraocular injections, laser therapy or vitrectomy for RVO were excluded from the study. Age, sex and geographically matched subjects were recruited as a control group from patients who presented for regular eye examinations at the same hospital during the study period. RESULTS: A total of 218 patients with RVO presented during the study period. The mean age of the patients was 61.1 + or - 12.3 years with more men (58.3%) than women. The mean age for control groups was 61.3 + or - 13.0 years. Seventy per cent of subjects had branch retinal vein occlusion, whereas central retinal vein occlusion was present in 26.6%. 63.9% of branch retinal vein occlusion was found in the superotemporal branch. Hypermetropia, primary open angle glaucoma, hypertension, mixed diabetes and hypertension, and heart disease were significantly higher in RVO cases as compared with the control group. CONCLUSION: The demographic characteristics, patterns and risk factors of RVO in Nepal can help guide interventions against these blinding diseases in similar developing countries. PMID- 20584018 TI - Relationship between retinal sensitivity and morphologic changes in eyes with confluent soft drusen. AB - PURPOSE: To examine the relationship between retinal sensitivity and morphologic changes in the macular area of eyes with confluent soft drusen. METHODS: We retrospectively reviewed the medical records of the 21 consecutive patients (22 eyes) who had confluent soft drusen in the macular area. Using spectral-domain optical coherence tomography, a 6 x 6-mm area of each macula was examined with 256 sequential horizontal scans. Microperimetry in the macular area was carried out using the Micro Perimeter 1. RESULTS: Spectral-domain optical coherence tomography images showed that protrusion of the retinal pigment epithelium (RPE) corresponded to the site of the confluent soft drusen. In addition, irregularities of the reflective line of the junction between inner and outer segments (IS/OS) of the photoreceptors were noted in 17 (77.3%) eyes. These irregularities were seen in the area with the protrusion of RPE. At 510 (68.1%) of 748 points with an intact retina, retinal sensitivity was 14 decibels or better. However, a retinal sensitivity of 14 decibels or better was obtained at 38.9% of points in irregular RPE with an intact IS/OS line, but at only 15.2% of points with an irregular IS/OS line. The mean retinal sensitivities within the area of irregular RPE with an intact IS/OS line, or in areas with an irregular IS/OS line, respectively, were significantly lower than that of intact retina (P < 0.0001). CONCLUSION: Eyes with confluent soft drusen often show focal areas with reduced retinal function, areas that are consistent with irregularity of the RPE or of the IS/OS line. PMID- 20584019 TI - Scleral perforation secondary to a spontaneously dehisced senile scleral plaque: clinical features and management. PMID- 20584020 TI - Comparative study of the retinal vessel anatomy of rhesus monkeys and humans. AB - OBJECTIVES: This study aims to compare retinal vessel anatomy of normal rhesus monkeys and humans and to provide a basis from a structural perspective for the use of rhesus monkey as an experimental model in future studies of retinal vessels. METHODS: The retinas of six normal rhesus monkey eyes and eight human eyecups following corneal transplantation were obtained and stained using adenosine diphosphatase methods. The distributions, orders, layers of the retinal vessels and the perifoveal vascular ring were compared. RESULTS: With adenosine diphosphatase staining, distinct retinal vessels were fully discernable from the first order surrounding the optic disc to the fifth order. There were no statistically significant differences between rhesus monkeys and humans in the percentages of vessels surrounding the optic disc at the equator and the peripheral region. Vascular networks in both species were arranged in several layers around the optic disc, two anastomotic layers at the equator and one sparse layer peripherally. Capillaries at the macular area were quite dense and an intact perifoveal vascular ring was observed. No differences were observed between rhesus monkeys and humans in the percentage area of the vessels and the area, perimeter and diameter of the perifoveal vascular ring. CONCLUSIONS: The distributions, orders, layers and the perifoveal vascular ring of the retinal vessels of rhesus monkey are quite similar to those of humans. The data suggest that from an anatomical perspective, the rhesus monkey is a good animal model for the study of human retinal vessels, particularly the macular capillaries. PMID- 20584021 TI - Insertion of the levator aponeurosis and Muller's muscle on the tarsus: a cadaveric study in Caucasians. AB - PURPOSE: To elucidate the insertion of the levator aponeurosis and Muller's muscle on the upper eyelid of Caucasians through cadaveric study. METHODS: Sagittal full thickness sections of 11 cadaveric upper eyelids in Caucasian (7 right and 4 left; age range, 78-101 years old at death; age average, 87.7 years old) were prepared and stained with Masson's trichrome. The specimens were examined microscopically to discern the configuration of the levator aponeurosis, Muller's muscle and tarsus. Main outcome measures were the position of insertion of the levator aponeurosis and Muller's muscle onto tarsus. RESULTS: In all 11 specimens, the levator aponeurosis inserted onto the distal tarsal plate, reaching the level of the marginal arterial arcade. The extension of Muller's muscle in 4/11 specimens (36.4%) surpassed the superior margin of the tarsal plates, but did not reach any further down the tarsus than its upper third; in the remaining seven specimens (63.6%), Muller's muscle attached to the superior aspect of the tarsal plate. CONCLUSIONS: This study from Caucasian cadavers suggests that fibres from the levator apponeurosis extends down to the distal portion of upper eyelid tarsus, with majority of Muller's muscle insertion being onto the superior aspect of the tarsal plate. PMID- 20584022 TI - Orbital bone and soft tissue calcification in CREST syndrome. PMID- 20584023 TI - High glucose-induced apoptosis in bovine retinal pericytes is associated with transforming growth factor beta and betaIG-H3: betaIG-H3 induces apoptosis in retinal pericytes by releasing Arg-Gly-Asp peptides. AB - BACKGROUND: Transforming growth factor beta (TGF-beta) plays an important role in diabetic retinopathy. betaIG-H3 is a downstream target molecule of TGF-beta that may participate in the pathogenesis of diabetic retinopathy and in particular in the loss of pericytes during early pathological changes. METHODS: We observed bovine retinal pericytes apoptosis and the increased expression of TGF-beta and betaIG-H3 induced by high concentrations of glucose in the cell culture media. An anti-TGF-beta antibody was used to block glucose-induced retinal pericytes apoptosis. Retinal pericytes were also transfected with cDNA encodings either wild-type or mutant betaIG-H3 lacking Arg-Gly-Asp (RGD) sequences in order to validate the effects of betaIG-H3 and RGD signalling on retinal pericytes apoptosis. RESULTS: A cell death-detecting enzyme-linked immunosorbent assay revealed that 25 mM glucose significantly increased cell death compared with 5.5 mM glucose after 5 or 7 days of exposure (P < 0.01). High glucose significantly increased the TGF-beta levels as compared with 5.5 mM glucose after 5 days, and betaIG-H3 levels after 3, 5 and 7 days of exposure (P < 0.01). TGF-beta increased cell death and betaIG-H3 levels in a dose-dependent manner, with a maximal effect observed at 1 ng/mL. An anti-TGF-beta antibody nearly completely blocked high glucose-induced cell death. Wild-type betaIG-H3-transfected cells showed a significant increase in cell death as compared with mutant betaIG-H3-transfected (Mycb-c) cells, untransfected or mock-transfected cells. CONCLUSION: These results suggest that hyperglycaemia-induced expression of TGF-beta and betaIG-H3 contributes to accelerated retinal pericytes apoptosis. betaIG-H3 induces pericytes apoptosis through its RGD motif, which may constitute an important pathogenic mechanism leading to pericytes loss in diabetic retinopathy. PMID- 20584024 TI - Cerebrospinal fluid secretion. PMID- 20584025 TI - Retinal haemorrhage in abusive head trauma. AB - Paediatric abusive head injury may have grave consequences, especially when characterized by repetitive acceleration-deceleration forces (shaken baby syndrome). Death occurs in approximately 30% and permanent neurologic damage in up to 80% of the victims. Retinal haemorrhages are a cardinal sign seen in approximately 85% of cases. In most cases haemorrhages are preretinal, intraretinal and subretinal, too numerous to count, and involving the entire retinal surface extending to the ora serrata. Traumatic macular retinoschisis is a lesion with important diagnostic significance. Vitreoretinal traction appears to be the mechanism of haemorrhage and schisis formation along with a possible role of orbital tissue trauma from repetitive acceleration-deceleration forces. Ophthalmologists must carefully document ocular findings. Appropriate autopsy examination should include ocular and orbital tissue removal. Although there is a wide differential diagnosis for retinal haemorrhages, clinical appearance, when considered in the context of systemic and laboratory findings, usually leads to the correct diagnosis. PMID- 20584026 TI - Calciphylaxis of the temporal artery masquerading as temporal arteritis. AB - We describe a case of a 75-year-old man with diabetes type II and end-stage renal disease, presenting with a one-month history of blurring of vision in the left eye. Fundus exam showed pale and swollen optic nerve in the left eye, and temporal artery biopsy showed diffuse and extensive calcification at the internal elastic lamina and media. Biopsy of dusky erythematous lesions over the calves revealed the diagnosis of calciphylaxis. The temporal artery calcific lesions should hence be differentiated from the less extensive atherosclerotic changes, which mainly affect the media of the artery, as it is crucial to suspect this life-threatening diagnosis in patients at risk. PMID- 20584027 TI - Clinical characteristics and outcome of current standard management of central retinal artery occlusion. AB - BACKGROUND: To investigate the visual outcomes in acute central retinal artery occlusion (CRAO) with current standard therapy at two university teaching hospitals. METHODS: Retrospective analysis of two cohorts of CRAO patients from John Hopkins Hospital (JHH; USA), and Flinders Medical Centre (FMC; Australia), treated with current standard therapy. The outcome measures were visual acuity, and subsequent ocular and systemic ischaemic events. RESULTS: The mean follow-up period was 11.2 +/- 13.1 months in the JHH cohort and 35.4 +/- 34.9 months in the FMC cohort. The frequency distribution of vascular risk factors and the incidence of subsequent ischaemic events were similar for the patients from both institutions. All patients from JHH were treated as inpatients, whereas 79% of patients from FMC were treated as outpatients. More patients in the JHH cohort underwent paracentesis, ocular massage or were treated with intraocular hypotensive agents (76%) than in the FMC cohort (26%); however, there was no significant difference in visual outcome between the two cohorts (P = 0.114). CONCLUSION: Despite differences in management of CRAO between two institutions in different countries, visual outcomes were similar. This suggests a lack of efficacy of current standard treatment in acute CRAO. PMID- 20584028 TI - Toric implantable collamer lens for patients with moderate to severe myopic astigmatism: 12-month follow-up. AB - PURPOSE: To report on the 12-month follow-up of 77 eyes with moderate to high myopic astigmatism implanted with toric implantable collamer lenses (ICLs). METHODS: Retrospective case-note review of 77 eyes from 42 patients undergoing toric ICL placement by one surgeon. Preoperative mean spherical equivalent -2.50 dioptres (D) to -15.00 D myopia and 1.00 D to 7.00 D astigmatism. RESULTS: At 12 months, mean manifest refractive cylinder (MRC) decreased 81% from 2.38 D to 0.44 D. MRC within 1.00 D occurred in 99% (76/77) of eyes, whereas 86% (66/77) had MRC within 0.75 D. 99% (76/77) had postoperative best-corrected visual acuity (BCVA) better than or equal to preoperative values, whereas 78% (60/77) gained up to one line BCVA and 1% (1/77) lost one line BCVA. Uncorrected binocular vision of 6/6 or better occurred in 90% (38/42) of patients compared with binocular BCVA of 6/6 or better in 67% (28/42) preoperatively. One ICL was replaced due to low vaulting. Two eyes with astigmatism of 3.25 D and 3.50 D received subsequent laser in situ keratomileusis (LASIK) to reduce residual small refractive errors. Indications for ICL were: myopia too high for LASIK (73%), cornea too thin for LASIK (44%) and contact lens intolerance (33%). Night halos were reported in 10% (8/77) of eyes at 12 months. One ICL was removed due to unrecognized preoperative glaucoma. There were no cases of cataract formation, or endophthalmitis. CONCLUSION: This study is the largest reported series of toric ICL implantation in New Zealand. It supports the safety, efficacy and predictability of toric ICLs to treat myopic astigmatism. PMID- 20584029 TI - Ancient origin of the CTH alelle carrying the c.200C>T (p.T67I) variant in patients with cystathioninuria. AB - Hereditary cystathioninuria is due to mutations in the CTH gene that encodes for cystathionase, a pyridoxal-5'-phosphate (PLP) dependent enzyme. To date, mutations in this gene have been described in 10 unrelated cystathioninuric patients. Enzyme assays have showed that mutated cystathionase exhibits lower activity than controls. As cystathioninuria is usually accompanied by a wide variety of symptoms, it has been questioned whether it is a disease or just a biochemical finding not associated with the clinical picture of these patients. This is the first report of Spanish patients with cystathioninuria and mild to severe neurological symptoms in childhood. After oral pyridoxine therapy biochemical parameters have normalized but clinical amelioration was not evident. All patients were homozygotes for the c.200C>T (p.T67I) variant which is the most prevalent inactivating mutation in the CTH gene. To further investigate the history of the alleles carrying the c.200C>T transition in Europe, we also constructed the haplotypes on the CTH locus in our Spanish patients as well as in a clinical series of cystathioninuric patients from the Czech Republic harboring the same nucleotide change. We suggest that the CTH p.T67I substitution could have an ancient common origin, which probably occurred in the Neolithic Era and spread throughout Europe. PMID- 20584030 TI - Parental origin of apparently balanced de novo complex chromosomal rearrangements investigated by microdissection, whole genome amplification, and microsatellite mediated haplotype analysis. AB - Complex chromosomal rearrangements (CCRs) are rare findings in clinical cytogenetics. As a result of the high risk of unbalanced segregation, familial cases are even rarer and maternal transmission occurs more frequently than paternal transmission. Analogous to Drosophila and mice, as well as to CCRs involving the Y chromosome or a clinically relevant associated deletion, a preferential origin in spermatogenesis has been assumed but not proven directly and systematically thus far. Here, we investigated three healthy adults, one healthy child, and one child with multiple congenital anomalies and various balanced de novo CCRs. The analyses were performed in each case on 10 copies of a derivative chromosome and their normal homologs by glass-needle microdissection, whole genome amplification (WGA), and microsatellite-mediated haplotype analysis. With respect to the number of chromosomes involved in each case and in all cases together, the number of chromosomal segments in each case and in all cases together, and the number of breakpoints in each case and in all cases together, the conformity for paternal origin of all derivative chromosomes and maternal origin of their normal homologs makes formation in paternal germline more likely than a postzygotic formation with an accidental uniformity. In conclusion, our results confirm the preferential formation of de novo balanced CCRs in the paternal germline. PMID- 20584031 TI - Novel splice-site mutations and a large intragenic deletion in PLA2G6 associated with a severe and rapidly progressive form of infantile neuroaxonal dystrophy. AB - Infantile neuroaxonal dystrophy, INAD, is a severe progressive psychomotor disorder with infantile onset and characterized by the presence of axonal spheroids throughout the central and peripheral nervous systems. A subset of INAD patients shows also brain iron accumulation which represents instead the distinctive feature of the idiopathic neurodegeneration with brain iron accumulation, NBIA. These diseases share the same causative gene, PLA2G6, encoding iPLA2-VIA, a calcium-independent phospholipase. Mutations that lead to a complete absence of protein are associated with a severe INAD profile, while compound heterozygous mutations with possibly a residual protein activity are instead associated with the less severe NBIA phenotype. Here we describe two INAD patients both with an unusually rapid disease progression and a peculiar neuroradiological presentation in one of them. Compound heterozygosity for a large intragenic deletion and a nonsense mutation was found in one of them while the other is carrying two novel splice-site mutations. Breakpoint-sequence analysis suggests a non-allelic-homologous-recombination (NAHR) event, probably underlying the rearrangement. These findings, while supporting the genotype phenotype correlation already observed in INAD patients, provide the first sequence characterization of a genomic rearrangement in PLA2G6 gene, thus orienting the search for missing mutant alleles in PLA2G6 related diseases. PMID- 20584032 TI - Reliability of the Respiratory Movement Measuring Instrument, RMMI. AB - INTRODUCTION: A new instrument to measure breathing movements, Respiratory Movement Measuring Instrument (RMMI), has been developed. There is still a lack of knowledge about the reliability of the instrument. OBJECTIVES: The aim was to investigate reliability of the RMMI. METHODS: In this trial, RMMI (ReMo Inc. Keldnaholt, Reykjavik, Iceland) was used. Inter- and intrarater reliability was performed on 30 volunteers who were tested three times in the supine position. Two of the tests were performed by one of the authors and the third test by the other. Intrasubject reliability was tested on 10 volunteers 12 times randomly during 1 h. Intra-instrument reliability was performed by measuring 12 solid surfaces where the instrument was placed horizontally against a couch or vertically against a chair. RESULTS: Intra-rater reliability: The correlations were moderate to strong (r = 0.54-0.94) except for the left lower thoracic position r = 0.35. Inter-rater reliability: The correlations were strong (r = 0.71-0.99) except for the left lower thoracic position r = 0.35. The strongest correlations were seen on the tests on abdominal breathing movements. Intra subject reliability: The over-all difference within and between the participants and test was non-significant (P = 0.98). The average difference between the tests was 1.4 mm. Intra instrument: The differences between the measurements were small (mean 0.15 mm). The over-all difference was non-significant (P = 0.79). CONCLUSION: The RMMI is a reliable instrument and usable in both clinical practice and research. PMID- 20584033 TI - Male-female differences in forearm skin tissue dielectric constant. AB - Tissue dielectric constant (TDC) measurements at 300 MHz via the coaxial line reflection method are useful to evaluate local skin tissue water and its change, but virtually all available data relate to measurements on women. Because TDC values in part depend on skin thickness, we hypothesized that differences in male female skin may be associated with male-female differences in TDC. To test this hypothesis, we compared TDC values in volar forearm skin of 60 young adult volunteers (30 men, 25.0 +/- 2.5 years, 30 women, 27.4 +/- 6.6 years) in the seated position using a probe with an effective measurement depth of 1.5 mm. Results showed that TDC values (mean +/- SD) for men were significantly greater than for women (33.2 +/- 4.0 versus 29.4 +/- 2.7, P<0.001) constituting an overall difference of about 13%. This finding suggests that when TDC measurements are used in research or clinical studies in which both men and women are included in a common study population, it would be prudent to consider this difference in both experimental design and data interpretation. This is especially true if absolute TDC values are of interest in contrast to changes in TDC values on the same subject subsequent to time passage or secondary to an intervention. Despite greater TDC values measured in men, calculations of the impact of a greater male skin thickness indicate that the greater TDC values of men may or may not reflect a greater relative local skin tissue water in men compared to women. PMID- 20584034 TI - Difficult pacemaker implantation. Detection of a wrong course due to sinus venosus type atrial septal defect. PMID- 20584035 TI - Analysis of the harmonized growth pattern of fetal organs by multidimensional scaling and hierarchical clustering. AB - The development of an organ may be affected by various growth and differentiation factors released from other organs. These factors are believed to have important effects on the development of multiple organs. To detect and analyze harmonized development among multiple organs, similarities in growth patterns among fetal organs were examined using multivariate analysis. Ninety human fetuses obtained from the Kyoto Collection of Human Embryos were dissected. Harmonized development of organs was evaluated by multidimensional scaling and cluster analysis using measurements (length, width, height, and weight) of the fetal organs. Similar growth patterns were observed between the brain, including cerebrum, diencephalon, and midbrain (cerebrum-to-midbrain [Cer-Mid]), and pituitary (crown rump length [CRL] 95-155 mm). Further, similar growth patterns were observed between the liver and Cer-Mid and cerebellum (Cb; CRL 156-202 mm), and between Cer-Mid and Cb (CRL 203-253 mm). Similarities in growth patterns were also observed between right and left lungs (CRL 99-235 mm) and between the aorta and heart (CRL 139-187 mm), but not between the lung and pulmonary trunk. These findings revealed synchronized development among fetal organs and suggested a functional and structural relationship among different organs in the prenatal period. These relationships include the existence of common factors in organ development, such as cross-talk mediated by humoral factors, and the presence of an anatomical and functional relationship in the fetal circulatory system. PMID- 20584036 TI - Isolation of the left subclavian artery from the pulmonary artery in a patient with CHARGE association. AB - A male infant diagnosed with CHARGE association presented with respiratory insufficiency and a cardiac murmur. Diagnostic evaluation showed a right sided aortic arch with an isolation of the left subclavian artery arising from the pulmonary artery through a left patent arterial duct. This is a rare cardiac disorder not previously described in patients with CHARGE association, detected with a 3D computed tomography scan, which emphasizes the importance of a thorough cardiac screening in patients with CHARGE association. PMID- 20584037 TI - Severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and hypoplastic left heart syndrome: proposal of a new syndrome. AB - Peters Plus syndrome is a very rare autosomal recessive condition characterized by ocular defects (typically Peters anomaly) and other systemic major/minor anomalies. Mutations in the B3GALTL gene encoding beta 1,3-glucosyltransferase have been found in virtually all patients with typical Peters Plus syndrome. We report on a female patient with unusually severe manifestations of Peters Plus syndrome, including anterior eye staphyloma, cleft lip and palate, and hypoplastic left heart syndrome (HLHS). Analysis of the B3GALTL gene revealed no mutation in the patient. To our knowledge, HLHS has not previously been reported in Peters Plus syndrome so far, and anterior staphyloma, a most severe defect of the anterior eye chamber, is also apparently rare in the syndrome. Our patient might represent a new syndrome of severe Peters Plus syndrome-like phenotype with anterior eye staphyloma and HLHS. PMID- 20584038 TI - Comparison of classification systems for congenital melanocytic nevi. AB - BACKGROUND: Congenital melanocytic nevi (CMNs) are found in approximately 1% of newborn infants, but these represent only a small proportion of the total population of nevi. They vary widely in size, from a small spot to a large area. Later in childhood, these lesions become thickened, verrucous, and hairy. Giant CMNs predispose to malignant melanoma, with a reported incidence of 2% to 31%. OBJECTIVE: To compare three different classification methods of the CMNs to determine which is most accurate. PARTICIPANTS AND METHODS: Sixty patients were included in the study (34 male, 26 female), with an average age of 17.4 (range 3 32). The nevi were evaluated using three different classification methods: total area of the nevus (in cm(2)), greatest nevus dimension, and percentage of nevus surface area to total patient body surface area. An appropriate treatment procedure for each case was applied, and participants were followed from 1997 to 2007. RESULTS: Malignant transformation was noted in 15.4% of participants with congenital nevi, which was confirmed histopathologically after excision. CONCLUSION: We recommend the calculation of total nevus area as the most useful method for assessment of the risk of developing melanoma in a CMN. The authors have indicated no significant interest with commercial supporters. PMID- 20584039 TI - Human immunodeficiency virus-associated lipohypertrophy (buccal fat pad lipoma like lesions) reduced with subcutaneously injected sodium deoxycholate. PMID- 20584040 TI - Treatment of erythromelanosis follicularis faciei et colli using a dual wavelength laser system: a split-face treatment. PMID- 20584041 TI - Pyogenic granuloma arising as a complication of 595 nm tunable pulsed dye laser treatment of port-wine stains: report of four cases. PMID- 20584042 TI - Venous-like leg ulcers without venous insufficiency in congenital anemia: successful treatment using compression bandages. PMID- 20584043 TI - A simple and effective treatment for ectopic sebaceous glands on the areola. PMID- 20584044 TI - Rapid progression of a basal cell carcinoma after photodynamic therapy. PMID- 20584045 TI - Plantar melanoma: is the prognosis always bad? PMID- 20584046 TI - A tunneled and turned-over nasolabial flap for reconstruction of full thickness nasal ala defects. PMID- 20584047 TI - Neurological complications in two children with Lemierre syndrome. AB - Lemierre syndrome is a distinct clinical syndrome comprising oropharyngeal sepsis and fever, internal jugular vein thrombosis and remote septic metastases caused by Fusobacterium species. The mortality rate was historically high and although use of antibiotics led to a dramatic fall in incidence, a resurgence has been seen recently. A 14-year-old male developed Lemierre syndrome after tonsillitis. There was extensive leptomeningitis, especially over the clivus, causing 6th and 12th cranial nerve palsies, a clinical feature termed the 'clival syndrome'. He also developed an epidural abscess in the cervical spine, which was unsafe for surgical drainage. Conservative treatment with an extended course of antibiotics and anticoagulation for jugular vein thrombosis led to a good recovery. A 15-year old female developed Lemierre syndrome after a persistent sore throat lasting 7 weeks. She had palsy of the 12th cranial nerve from clival osteomyelitis. She was treated with a 6-week course of antibiotics and anticoagulants leading to almost full recovery at 3-month review. Awareness of the potential neurological complications of Lemierre syndrome and prompt management are crucial in reducing morbidity and mortality in this 'forgotten disease'. PMID- 20584048 TI - Epilepsy in hemiplegic cerebral palsy due to perinatal arterial ischaemic stroke. PMID- 20584049 TI - Why are children with cerebral palsy more likely to have emotional and behavioural difficulties? PMID- 20584050 TI - Paroxysmal disorders in infancy: a diagnostic challenge. PMID- 20584051 TI - 3D echocardiographic delineation of mitral-aortic intervalular fibrosa pseudoaneurysm caused by bicuspid aortic valve endocarditis. AB - Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare complication of infective endocarditis of the aortic valve eventually resulting in coronary artery compression, stroke or rupture into the left atrium, aorta or pericardial space. A prompt diagnosis by either transthoracic or transesophageal echocardiography is mandatory to address the patient to cardiac surgery. We report the clinical case of a 25-year-old white man who was admitted to the emergency department for dyspnoea and fever. Echocardiographic examination showed a bicuspid aortic valve with a huge sessile vegetation and a pseudaneurysm of the mitral-aortic intervalvular fibrosa. In addition to conventional two-dimensional examination, three-dimensional echocardiography provided additional information of this complication, precisely delineating the lesions and addressing the cardiac surgeon in choosing the most appropriate operating strategy. Patient underwent then aortic root replacement and the pseudoaneurysm was closed by means of a bovine pericardial patch. PMID- 20584052 TI - Role of contrast-enhanced transesophageal echocardiography for detection of and scoring intrapulmonary vascular dilatation. AB - BACKGROUND: Intrapulmonary vascular dilatations (IVD) are microvascular pulmonary changes mediated by nitric oxide that cause right-to-left shunt and hypoxemia. Contrast-enhanced transthoracic echocardiography (cTTE) is the gold standard diagnostic test for IVD. OBJECTIVE: To evaluate contrast-enhanced transesophageal echocardiography (cTEE) in the diagnosis and grading of IVD. METHODS: A study group (SG) of 63 cirrhotic patients were compared to 20 shunt-free control subjects (CG). Both groups underwent cTEE and cTTE using intravenous injections of agitated saline solution for contrast tests. Patients with patent foramen ovale, when detected, were excluded. Late appearance of microbubbles in the left atrium was diagnostic of pulmonary shunt (positive contrast test) and was graded as trivial, mild, moderate or severe by cTEE. Contrast tests were negative in 7 patients (35%) and trivial in the remaining 13 (65%) in CG, so only contrast grades >= mild were considered to be positive IVD tests in the SG. Gasometric change was expressed as the alveolar-arterial oxygen tension difference (A-aO2D) and was considered abnormally high at values >20 mmHg. RESULTS: SG: positive IVD tests were present in 23 patients (36%) by cTTE and 47 (75%) by cTEE (P < 0.001). These patients showed A-aO2D values significantly higher than those with negative IVD tests (P < 0.02) and were directly proportional to the contrast grade. cTEE allowed the diagnosis of IVD in three additional patients with high A-aO2D that were not detected by cTTE. CONCLUSION: cTEE enabled diagnosis of IVD in a greater number of patients with gasometric changes compared to cTTE. The contrast effect grade by cTEE seems to be proportional to IVD magnitude. PMID- 20584053 TI - Atrial Septal Defect Occluder Device Huge Thrombus in Patient with Low Ejection Fraction. PMID- 20584054 TI - Differences in left ventricular twist related to age: speckle tracking echocardiographic data for healthy volunteers from neonate to age 70 years. AB - OBJECTIVE: To determine normal left ventricular (LV) twist characteristics in different age groups and assess changes between neonates and the elderly. METHODS: Short-axis left ventricle images at basal and apical levels were acquired in 274 healthy volunteers (aged 15 days to 72 years) by two-dimensional echocardiography, and were analyzed off-line using Speckle tracking echocardiography (STE) software to obtain LV twist measurements. The peak apical rotation (PAr), peak basal rotation (PBr), peak LV twist (Ptw), peak LV twist normalized by LV length (PtwN), peak untwisting velocity (PutwV), and isovolumic untwisting% (Iutw%) were measured. RESULTS: LV twist values vary with age. Ptw was higher in older volunteers. PtwN varied inconsistently with age. PutwV and Iutw% were lower in the young and old with a peak in mid-age ranges. CONCLUSIONS: STE is an effective noninvasive method to assess LV twist. Age-related differences in LV twist may reflect maturation and adaptive modulation of LV torsional biomechanics from neonate to the elderly. PMID- 20584055 TI - Three-dimensional transthoracic echocardiography in identification of aorto-right atrial fistula and aorto-right ventricular fistulas. AB - We report the case of a 72-year-old woman who developed new onset right ventricular failure after redo aortic valve replacement. The diagnosis of left to right shunt was initially made using two-dimensional transthoracic echocardiography (2DTTE) and 2D transesophageal echo with color Doppler (TEE). Definite diagnosis of aorto-right atrial and aorto-right ventricular fistula was made using three-dimensional transthoracic echocardiography (3DTTE) with color flow Doppler imaging. Early recognition and diagnosis of this rare surgical complication is imperative for prompt surgical repair of this lethal defect. 3DTTE should be utilized in cases of new onset heart failure with unclear etiology to diagnose unusual causes of this potentially fatal condition. PMID- 20584056 TI - Recovery of long-axis left ventricular function after aortic valve replacement in patients with severe aortic stenosis. AB - BACKGROUND: Patients with aortic stenosis (AS) should undergo aortic valve replacement (AVR) before irreversible LV dysfunction has developed. Assessment of long-axis left ventricular (LV) function may assist in proper timing of AVR. OBJECTIVES: To assess serial changes in long-axis LV function before and after AVR in patients with severe AS and preserved LV ejection fraction. METHODS: The study comprised 27 consecutive patients (mean age 64.9 +/- 11.7 years, 15 males) with symptomatic severe AS, scheduled for AVR. Seventeen subjects without known cardiac disease, matched for age, gender, LV ejection fraction and cardiovascular risk factors, served as a control group. Long-axis LV function assessment was done with tissue Doppler imaging at 3 weeks, 6 months, and 12 months after AVR. RESULTS: Mean aortic valve area in the AS group was 0.70 +/- 0.24 cm2. Pre-AVR peak systolic mitral annular velocities were significantly lower compared to controls (6.7 +/- 1.5 vs. 8.9 +/- 2.0 cm/s, P < 0.05). Post-AVR peak systolic mitral annular velocities improved to 9.1 +/- 2.9 at 3 weeks, 8.6 +/- 2.7 at 6 months, and 8.1 +/- 1.7 cm/s at 12 months (P < 0.05). Improvements were seen over the whole range of pre-AVR peak systolic mitral annular velocities. Patients with improved Sm after AVR (defined as >= 10% compared to baseline values) did not differ in baseline characteristics as compared to those who did not improve. CONCLUSIONS: In patients with severe AS and preserved LV ejection fraction, abnormal systolic mitral annular velocities improve after AVR, independent of the pre-AVR value. PMID- 20584057 TI - Routine screening for abdominal aortic aneurysm during clinical transthoracic echocardiography in a Korean population. AB - BACKGROUND: An abdominal aortic aneurysm (AAA) is potentially fatal when ruptured. Whereas the transthoracic echocardiography (TTE) protocol does not routinely include examination of the infrarenal abdominal aorta, the protocol is performed quickly and easily for AAA screening. AIM: The aim of this study was to evaluate the clinical utility of the protocol for AAA screening during TTE in a Korean population referred for clinical TTE. METHODS: All of the patients who were scheduled for TTE were enrolled in the study. At the end of TTE protocol, the abdominal aorta was evaluated at the level below the renal artery origin. RESULTS: A total of 6,267 patients were screened, and the abdominal aortas were visualized in 79% (4,939 patients) of patients screened. AAA was diagnosed in 27 patients, 23 of whom were male. The mean age of AAA patients was 66.5 years old, and 81% of AAA patients were over 60 years old. The presence of AAA was associated with male gender and older age, as well as with hypertension and smoking. Of the 27 patients, 11 patients (0.2% of the study population) did not have a history of AAA screening and were newly diagnosed by TTE. CONCLUSIONS: Screening of AAA during TTE is easy and feasible. Even though the prevalence of AAA in patients is very low, detection of asymptomatic AAA may save lives. Therefore, opportunistic examination of the abdominal aorta during routine TTE, which involves little time and cost, would appear to be effective, at least in patients over 60 years of age, especially in men. PMID- 20584058 TI - Noninvasive assessment of left ventricular stroke work index in patients with severe mitral regurgitation: correlation with invasive measurement and exercise capacity. AB - BACKGROUND: Noninvasively measured left ventricular stroke work index (LVSWI) may be an ideal indicator that can provide more relevant information about cardiac performance in severe mitral regurgitation (MR). We sought to correlate the noninvasive LVSWI with invasive measure of LVSWI and validate its clinical usefulness by comparing the noninvasive LVSWI with exercise capacity. METHODS: Twenty-nine patients with severe MR who underwent cardiac catheterization and 61 patients with severe MR who underwent cardiopulmonary exercise test were evaluated for comparison of noninvasive LVSWI with invasive LVSWI via cardiac catheterization and peak exercise capacity, respectively. RESULTS: Mean noninvasive LVSWI was 33.1 +/- 9.7 g.m/m2, which was in a good agreement with invasive LVSWI (34.9 +/- 15.1 g.m/m2, intraclass correlation coefficient = 0.72, P < 0.001). Noninvasive LVSWI (beta= 0.35, P = 0.001) was independently related with peak exercise capacity. Indexed left atrial volume (beta=-0.27, P = 0.042), mean blood pressure (beta=-0.21, P = 0.030), age (beta=-0.47, P < 0.001) estimated pulmonary artery systolic pressure (beta=-0.21, P = 0.030) and male gender (beta= 0.36, P = 0.001) were also independently associated with exercise capacity. CONCLUSIONS: Noninvasive LVSWI has a good correlation with invasively measured LVSWI and is a clinically useful parameter for evaluating true cardiac performance in patients with severe MR. PMID- 20584059 TI - Dynamic circle image in left ventricle outflow tract. AB - A 46-year-old man presented with a complaint of effort dyspnea. On transthoracic echocardiography a circle appeared in LVOT. It was seen freely floating, disappearing in every systole and appearing again in diastole. Turbulence was seen inside the circle with color Doppler. Transesophageal echocardiography showed aortic cusps and their coaptation to be normal. Aortic root diameters were normal at the annulus, sinus of Valsalva, and sinotubular junction. There were no signs of dissection, infective endocarditis or abscess. But as the probe was advanced, left sinus of Valsalva was found to be prolapsed, and ruptured into LVOT. PMID- 20584060 TI - The utility of dobutamine stress echocardiography for the diagnosis of coronary artery disease in the HIV population. AB - BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has increased human immunodeficiency virus (HIV) patient longevity by 10-15 years. This increased longevity has habituated new cardiovascular complications, in particular, accelerated coronary artery disease (CAD). Although dobutamine stress echocardiography (DSE) is a highly sensitive and specific test for the noninvasive detection of underlying CAD in the general population, its utility in the HIV population remains unknown. OBJECTIVE: The objective of the current study was to assess the validity of DSE for the noninvasive detection of underlying symptomatic CAD in the HIV population using cardiac catheterization as the gold standard. METHODS AND RESULTS: A total of 40 HIV positive patients (mean 49 +/- 8 years; 31 males) between 2006 and 2009 inclusively underwent routine DSE and coronary angiography. A positive stress echo with new wall motion abnormalities was detected in 9 (23%) individuals. Coronary angiography, following DSE, detected obstructive CAD in 12 (30%) individuals. For the diagnosis of obstructive CAD, DSE has a sensitivity of 67%, specificity of 97%, positive predictive value (PPV) of 89%, and negative predictive value (NPV) of 87%. CONCLUSION: In this select HIV population, DSE was highly specific for the noninvasive detection of obstructive CAD. PMID- 20584061 TI - Cardiac autonomic function and global left ventricular performance in autoimmune eauthyroid chronic thyroiditis: is treatment necessary at the euthyroid stage? AB - OBJECTIVE: Autoimmune chronic thyroiditis (ACT) is characterized by lymphocyte infiltration in the thyroid gland and the presence of antithyroid antibodies in serum. Medical treatment does not affect antibody levels and treatment decision is not definite yet for the euthyroid patients. We aimed to evaluate cardiac autonomic function and global left ventricular performance in autoimmune euthyroid chronic thyroiditis and determine the need for medical treatment. METHOD: We studied 30 ACT patients and 25 healthy control subjects. Cardiac autonomic function is evaluated by heart rate recovery (HRR). Global left ventricular performance is evaluated by two-dimensional echocardiography and pulsed-wave tissue Doppler echocardiography. RESULTS: There was no difference between patients and controls with respect to clinical and biochemical parameters except hemoglobin (13.67 +/- 1.25 g/dL, 14.51 +/- 1.35 g/dL, p:0.047) and low density lipoprotein (120.71 +/- 24.91 mg/dL, 100.55 +/- 14.73 mg/dL, p: 0.003). Tei index was significantly higher in ACT group (0.521 +/- 0.074, 0.434 +/- 0.034, P < 0.0001). E'/A' was found to be significantly lower (1.234 +/- 0.42, 1.750 +/- 0.291, P < 0.0001) and E/E' was found to be higher than the controls (8.482 +/- 0.449, 6.039 +/- 0.209, P < 0.0001). HRR was significantly lower than the controls (20 +/- 4 BPM, 30 +/- 8 BPM, P < 0.0001). CONCLUSION: Although left ventricular performance is found to be normal by conventional echocardiographic methods, it is found to be impaired when Tei index and tissue Doppler parameters are used. Cardiac autonomic function is also impaired in ACT patients. As a result of these cardiac changes, medical treatment may be considered earlier, even at the euthyroid stage. PMID- 20584062 TI - A novel two-dimensional echocardiographic finding in cardiac amyloidosis. AB - BACKGROUND: A number of echocardiographic findings characteristic of cardiac amyloidosis (CA) have been described, each with limitations. METHODS: A distinctive wall motion pattern of preserved myocardial thickening at left ventricular apex with hypokinesis in basal and midsegments was observed in two patients with biopsy proven CA. Following this observation, endomyocaradial biopsy files beginning in 2007 were reviewed. Seven consecutive patients with documented CA were identified. Two-dimensional (2D) echocardiograms for each were reviewed in consensus by two experienced echocardiographers. Clinical and electrocardiographic data were obtained from chart review. RESULTS: All patients were men with class II-IV heart failure. Six had light chain CA, 1 senile CA. Six patients had coronary angiography. One had a 60% left anterior descending coronary artery stenosis. Five had nonobstructive disease. Echocardiograms for all seven patients demonstrated the distinctive pattern of preserved myocardial thickening at apex with hypokinesis in basal and midsegments. Reduced ejection fraction was present in six and increased wall thickness and myocardial echogenicity in seven. Other echo signs of amyloid were variably present. Three had low voltage on electrocardiogram. CONCLUSION: A distinctive 2D echocardiographic pattern of preserved segmental wall motion at left ventricular apex with hypokinesis in basal to midsegments was consistently identified in seven consecutive patients with endomyocardial biopsy-proven CA. PMID- 20584063 TI - Single-beat determination of right ventricular function in patients with atrial fibrillation. AB - BACKGROUND: In atrial fibrillation (AF), left ventricular (LV) systolic function positively correlates with the ratio of the preceding to prepreceding RR intervals (RRp/RRpp) and single-beat determination of LV function at a beat with equal RRp and RRpp closely estimates the average value over all cardiac cycles. The study was designed to evaluate the feasibility of single-beat determination that was based on the ratio of RRp/RRpp to accurately assess RV function in AF. METHODS: In 60 patients with AF, RV fractional area change (RVFAC), RRp and RRpp were measured during 20 beats for each patient. The relationship between RVFAC and RRp/RRpp was evaluated by linear regression analysis. The measured values of RVFAC at the beats with equal RRp and RRpp were compared with the average values over 20 beats. The influence of RRp cycle lengths on the values of RVFAC at the beats with equal RRp and RRpp was examined from the plot of normalized value against RR intervals. RESULTS: There were a positive linear relationship between RVFAC and RRp/RRpp in all patients (P < 0.001 in all). The RVFAC measured by single-beat method and cycle lengths < 500 ms were usually far below the average values. After excluding beats with cycle lengths < 500 ms, RVFAC determined by single-beat method was very close to the average values (y = 0.96x + 1.91%, r = 0.961; P < 0.001; bias 0.26%). CONCLUSIONS: RV FAC correlates positively with RRp/RRpp and single-beat determination of RV function is feasible and accurate in patients with chronic AF. PMID- 20584064 TI - Performance of echocardiographic parameters in sequential monitoring of left ventricular function in an animal model of acute heart failure. AB - INTRODUCTION: Numerous newer parameters have been established for sensitive and reproducible evaluation of left ventricular (LV) dysfunction. We assessed the performance of these parameters in sequential monitoring of LV function in an animal model of controllable drug-induced LV dysfunction. METHODS: To establish predictable aggravating LV dysfunction, seven male beagle dogs were anesthetized and received intermittent injection of esmolol and propofol of gradually increasing dosage. Parameters reflecting LV function were measured after each drug infusion. These included LV ejection fraction (LVEF) measured by both two dimensional (2D) and three-dimensional (3D) echocardiography, Tei index, ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') and 2D strain-derived parameters. Changes in these parameters over time were compared with the baseline value. RESULTS: Changes in 2D and 3D LVEF were observed after infusion with propofol (5 mg/kg) and esmolol (3.5 mg/kg). Doppler-derived parameters including E/e' and the Tei index failed to detect LV dysfunction prior to 2D LVEF. Significant changes in 2D strains and strain rates (SRs) could be induced by relatively small anesthetic dosages (~4 mg propofol/kg and 2.5 mg esmolol/kg). Strain-derived parameters were generally highly reproducible and longitudinal strain had the best intraobserver and interobserver reproducibility. CONCLUSIONS: The 2D strain parameters provide accurate identification of subclinical impairment of LV function earlier than all other echocardiographic indices. PMID- 20584065 TI - Cystic mass in interventricular septum; a rare presentation of sinus of Valsalva aneurysm. AB - A young male presented with progressively increasing breathlessness for one year. Echocardiography showed a cystic echolucent cavity in interventricular septum communicating with sinus of Valsalva. A diagnosis of unruptured aneurysm of Valsalva dissecting into the interventricular septum was made. This complication is extremely rare and early recognition may prevent a potential catastrophe. PMID- 20584066 TI - Impact of myocardial acceleration during isovolumic contraction in evaluating subclinical right ventricular systolic dysfunction in type 2 diabetes mellitus patients. AB - AIM: In diabetes mellitus (DM) patients, left ventricular dysfunction is widely evaluated and established by conventional diagnostic methods, whereas right ventricular (RV) function is not as sufficiently evaluated. The aim of this study is to assess the preclinical effects of DM on RV function by using novel Tissue Doppler Imaging (TDI)-derived indices. METHODS: The study included 96 patients with type II DM [60 with DM only and 36 patients with coexisting DM and hypertension (DMHT)] and 40 healthy controls. Conventional parameters and TDI derived systolic velocities of tricuspid annulus [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), RV Tei index] were measured. RESULTS: TDI-derived RV IVA was significantly lower in both DM and DMHT patients compared to controls indicating subclinical impairment in RV systolic function in the study patients (P = 0,0001). However RV IVA was similar in DM and DMHT subgroup supporting RV systolic impairment in DM was independent from HT. In correlation analysis, RV IVA was significantly correlated with the existence of diabetic nephropathy (r =-0,38; P = 0,003), retinopathy (r =-0,35; P = 0,006), insulin resistance (r =-0,52; P = 0,0001). CONCLUSIONS: Diabetes is associated with subclinical RV systolic dysfunction, regardless of coexisting hypertension. Tissue Doppler-derived IVA; is a novel, non-invasive parameter which may be used in early detection of RV systolic dysfunction in patients with DM. PMID- 20584067 TI - Assessment of left ventricular volumes and function by real time three dimensional echocardiography in a pediatric population: a TomTec versus QLAB comparison. AB - BACKGROUND: Three-dimensional echocardiography (3DE) allows accurate calculation of ventricular volumes despite a remaining geometric assumption on the ventricular shape. Few studies involving full volume reconstruction software have been performed on children. Our aim was to compare the left ventricular (LV) volume measurements obtained with the most used 3D analysis software in a pediatric population. METHODS: Fifty patients (median age: 9.5 years) without cardiac disease were included in the study. 3DE was performed with the X4-2 or X7 2 matrix probe (ie33, Philips). The LV volume analysis was performed with QLAB 6.0 (semiautomated border detection) and TomTec 4D LV (primary manual tracking with semiautomated border detection). RESULTS: TomTec analysis feasibility amounted to 94% whereas QLAB analysis feasibility only reached 80% (P = 0.037). The analysis time was shorter with QLAB than TomTec (5 +/- 2 versus 6 +/- 3 minutes, P < 0.05). The stroke volume, end diastolic and end systolic LV volume measurements performed on the 40 patients were strongly correlated (r > 0.97; P < 0.0001) with minimal bias. The LV ejection fraction was well correlated (r = 0.79; P < 0.0001). CONCLUSION: 3D LV volume quantification is feasible either by using manual or automated reconstruction software in a normal pediatric population. LV Measurements are well correlated. Differences in volume reconstruction algorithms provide specific software performance characteristics. TomTec is a more feasible method but requires a longer analysis time. Further studies are needed to validate the accuracy of the method to calculate enlarged LV volumes in patients with congenital heart diseases. PMID- 20584068 TI - Myocardial strain characterization in different left ventricular adaptative responses to high blood pressure: a study based on 3D-wall motion tracking analysis. AB - BACKGROUND: High blood pressure increases left ventricular (LV) after-load. Furthermore, LV response to that high blood pressure varies among different subjects. Nevertheless, myocardial deformation behavior in these different adaptative responses has not been analyzed until now. METHODS: Prospective study in which 66 consecutive hypertensive patients were enrolled in between May and August 2009. Every patient underwent a standard echocardiographic study and a three-dimensional-wall motion tracking (3D-WMT) study. The patients were classified according to parameters derived from echocardiography in four different groups: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: Mean age was 68 years (57-74.25; 51.5% male). Comparing the four groups, significant differences were found for the five 3D-WMT-derived parameters. When patients were compared with hypertensive patients with normal geometry, our finding show that: (a) LV average torsion is the only impaired parameter that is found in the LV concentric remodelling group (P < 0.05 vs. group 1); (b) there is a trend for an increase (P = 0.055) in LV average radial strain in the group with concentric hypertrophy and this increase is accompanied by a significant decrease in the remaining studied parameters (P < 0.05); and (c) in the LV eccentric hypertrophy group, there is a significant impairment in all the studied parameters (P < 0.05). CONCLUSIONS: LV adaptative response to hypertension is accompanied by a modification or even impairment, in LV myocardial deformation evaluated by 3D-WMT. This assessment might be useful to detect early and subtle deformation impairments in hypertensive patients and it could help optimize their clinical management. PMID- 20584069 TI - Echocardiographic determinants of the clinical condition in patients with a systemic right ventricle. AB - BACKGROUND: Ventricular systolic and diastolic function, as measured by echocardiography, are diminished in patients with a systemic right ventricle (RV). As the clinical implications of these finding remained unknown, we aimed to identify echocardiographic parameters of systolic and diastolic ventricular function that are independent determinants of the clinical condition in these patients. METHODS: Forty-six adult patients (61% male; mean age 33 [range 18-69] years) with a systemic RV underwent echocardiography to assess qualitative and quantitative systolic and diastolic function of the systemic RV and the subpulmonary left ventricle (LV). Uni- and multivariate linear regression analyses were performed to identify independent echocardiographic determinants for NYHA class, maximal exercise capacity (V'O(2peak)) and NT-proBNP levels. RESULTS: We found qualitative assessment of RV and LV function to be significantly associated with NYHA class (RV: beta= 0.26; P = 0.05 and LV: beta= 0.82; P < 0.01), V'O(2peak) (RV: beta=-10.4; P < 0.05 and LV: beta=-18.4; P < 0.05) and NT-proBNP levels (RV: beta= 0.58; P < 0.01 and LV: beta= 1.40; P < 0.001). Tricuspid annulus plane systolic excursion (TAPSE) was significantly associated with NYHA class (beta=-0.92; P = 0.001), V'O(2peak) (beta= 18.5; P = 0.05), and serum NT-proBNP levels (beta=-1.00; P < 0.05). Associations between quantitative parameters of systolic subpulmonary LV function and clinical parameters were less distinct. We found no associations between RV and LV diastolic function and clinical parameters. CONCLUSIONS: Qualitative function of the systemic RV and the subpulmonary LV, and TAPSE, are determinants of clinical condition in patients with a systemic RV. These patients' clinical condition could not be determined by echocardiographically measured diastolic RV function, and systolic and diastolic LV function. PMID- 20584070 TI - Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease. AB - BACKGROUND: Blocking the renin-angiotensin system (RAS) with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors protects against renal injury in patients with chronic kidney disease (CKD). The aim of this study was to compare the chronic effects of telmisartan and enalapril on proteinuria, urinary liver-type fatty acid-binding protein (L-FABP) and endothelin (ET)-1 levels in patients with mild CKD. MATERIALS AND METHODS: Thirty CKD patients with mild to moderate renal insufficiency (20 men and 10 women; mean age, 37 years; estimated glomerular filtration rate (eGFR) > 60 mL min(-1) and blood pressure > 130/85 mmHg) were included in the study. Patients were randomly assigned to receive telmisartan at 80 mg day(-1) (n = 15) or enalapril at 10 mg day(-1) (n = 15). We measured blood pressure, serum creatinine, eGFR, urinary protein, L-FABP and ET-1 before the start of treatment and 6 and 12 months after the start of treatment. RESULTS: The blood pressure reduction rate was similar between the two groups. Urinary protein, L-FABP and ET-1 levels were significantly reduced in both groups 6 and 12 months (P < 0.001) after treatment, but the reduction rates were more pronounced in patients receiving telmisartan than in those receiving enalapril (P < 0.001). Estimated glomerular filtration rate was increased similarly in both groups at 12 months. CONCLUSIONS: The study results suggest that telmisartan results in a greater reduction of urinary markers than does enalapril and that this effect occurs by a mechanism independent of blood pressure reduction. It would be needed to investigate whether the differences may be distinct or not the same when other dosages are used. PMID- 20584071 TI - Role of glucocorticoid receptor polymorphism in adrenal incidentalomas. AB - BACKGROUND: Adrenal incidentalomas (AI) have been associated with and an increased prevalence of metabolic and bone complications. The N363S and BclI polymorphisms of the glucocorticoid receptor (GR) have been associated with an increased sensitivity to glucocorticoid (GC). This observational study aims to evaluate whether BclI and N363S polymorphisms play a role in the development of complications in AI. MATERIALS AND METHODS: We enrolled 100 patients with AI (66 F; 34M). The presence of diabetes, arterial hypertension (AH), dyslipidaemia, osteoporosis and vertebral fracture (Fx), waist circumference and the Body Mass Index (BMI) were assessed. DNA samples were genotyped. Patients with wild-type BclI, wild-type N363S and heterozygous BclI polymorphism were classified as carriers of haplotype 1 (H1; n = 86), patients with homozygous BclI and heterozygous N363S polymorphism of GR of haplotype 2 (H2; n = 14). RESULTS: We found no clinical or biochemical differences between haplotype 1 and 2 groups, but a higher prevalence of the simultaneous presence of Fx plus AH in H2 patients (H2 n = 7, H1 n = 16, P = 0.01). Logistic regression analysis showed that the presence of Fx and of AH and the combination of the presence of Fx plus AH were associated with the H2 genotype regardless of the degree of cortisol secretion, age, BMI and BMD (OR 4.88, 95%CI 1.47-18.40, P = 0.05; OR 8.25, 95%CI 0.98-69.52, P = 0.05; OR 7.25, 95%CI 1.57-35.78, P = 0.011; respectively). CONCLUSIONS: In AI patients, the presence of the haplotype 2 of BclI and N363S is associated with the presence of AH, Fx and with the combination of Fx and AH. PMID- 20584072 TI - Nuclear and mitochondrial sequence data reveal and conceal different demographic histories and population genetic processes in Caribbean reef fishes. AB - Mitochondrial and nuclear sequence data should recover historical demographic events at different temporal scales due to differences in their effective population sizes and substitution rates. This expectation was tested for two closely related coral reef fish, the tube blennies Acanthemblemaria aspera and A. spinosa. These two have similar life histories and dispersal potentials, and co occur throughout the Caribbean. Sequence data for one mitochondrial and two nuclear markers were collected for 168 individuals across the species' Caribbean ranges. Although both species shared a similar pattern of genetic subdivision, A. spinosa had 20-25 times greater nucleotide sequence divergence among populations than A. aspera at all three markers. Substitution rates estimated using a relaxed clock approach revealed that mitochondrial COI is evolving at 11.2% pairwise sequence divergence per million years. This rapid mitochondrial rate had obscured the signal of old population expansions for both species, which were only recovered using the more slowly evolving nuclear markers. However, the rapid COI rate allowed the recovery of a recent expansion in A. aspera corresponding to a period of increased habitat availability. Only by combining both nuclear and mitochondrial data were we able to recover the complex demographic history of these fish. PMID- 20584073 TI - The evolution of spite: population structure and bacteriocin-mediated antagonism in two natural populations of xenorhabdus bacteria. AB - Spite occurs when an individual harms itself in the act of harming other individuals. Such behaviors were once assumed to be of limited evolutionary importance, as the conditions for the evolution of spite were thought to be too restrictive. Recent theoretical work, however, suggests that spatial population structure, which allows local competition among genotypes, could favor the evolution of spite. One of the clearest examples of spite is the costly production and release by bacteria of toxins (called bacteriocins) that can kill unrelated strains of the same species. Here, we establish the existence of spatial structure in two natural populations of bacteriocin-producing bacteria. Specifically, relatedness decreased with increasing spatial distance between the field isolates. In addition, toxin-mediated inhibitions were found only between isolates that were collected more than 1 m apart and that were generally less than 80% similar in their genomic fingerprints. Taken together, the results suggest that the bacteria are spatially structured, with mixing of genotypes and spiteful interactions at the boundaries between demes. PMID- 20584074 TI - The cost of sexual signaling in yeast. AB - The handicap principle holds that costly sexual signals can reliably indicate mate quality. Only individuals of high quality can afford a strong signal--the cost of signaling is relatively lower for high-quality signalers than for low quality signalers. This critical property is difficult to test experimentally because the benefit of signaling on mating success, and cost of signaling on other components of fitness, cannot easily be separated in obligate sexual organisms. We therefore studied the facultatively sexual yeast Saccharomyces cerevisiae, which produces pheromones to attract potential mates. To precisely measure the cost of signaling, the signal was reduced or removed by deleting one or both copies of the pheromone-encoding genes and measuring asexual growth rate in competition with a wild-type signaler. We manipulated signaler quality either by changing the quality of the assay environment or by changing the number of deleterious mutations carried. For both types of treatment, we found that the cost of signaling decreased as the quality of the signaler increased, demonstrating that the yeast pheromone signal has the key property required for selection under the handicap principle. We found that cells of high genetic quality produce stronger signals than low-quality cells, verifying that the signal is indeed honest. PMID- 20584076 TI - Organizational constraints on Ste12 cis-elements for a pheromone response in Saccharomyces cerevisiae. AB - Ste12 of Saccharomyces cerevisiae binds to pheromone-response cis-elements (PREs) to regulate several classes of genes. Genes induced by pheromones require multimerization of Ste12 for binding of at least two PREs on responsive promoters. We have systematically examined nucleotides of the consensus PRE for binding of wild-type Ste12 to DNA in vitro, as well as the organizational requirements of PREs to produce a pheromone response in vivo. Ste12 binds as a monomer to a single PRE in vitro, and two PREs upstream of a minimal core promoter cause induction that is proportional to their relative affinity for Ste12 in vitro. Although consensus PREs are arranged in a variety of configurations in the promoters of responsive genes, we find that there are severe constraints with respect to how they can be positioned in an artificial promoter to cause induction. Two closely-spaced PREs can induce transcription in a directly-repeated or tail-to-tail orientation, although PREs separated by at least 40 nucleotides are capable of inducing transcription when oriented in a head-to-head or tail-to-tail configuration. We characterize several examples of promoters that bear multiple consensus PREs or a single PRE in combination with a PRE-like sequence that match these requirements. A significant number of responsive genes appear to possess only a single PRE, or PREs in configurations that would not be expected to enable induction, and we suggest that, for many pheromone-responsive genes, Ste12 must activate transcription by binding to cryptic or sub-optimal sites on DNA, or may require interaction with additional uncharacterized DNA bound factors. PMID- 20584077 TI - Solution properties of full-length integrin alpha(IIb)beta3 refined models suggest environment-dependent induction of alternative bent /extended resting states. AB - The recently published novel integrin alpha(IIb)beta(3) ectodomain crystallographic structure and NMR structures of its transmembrane/cytoplasmic segments were employed to refine previously developed molecular models. Alternative complete alpha(IIb)beta(3) models were built and evaluated, and their shape was compared with EM maps and their computed hydrodynamic/conformational properties were compared with the available experimental data. A partially extended/closed model, or a mixture of bent/closed and extended/closed conformations, are both compatible with the results of a recent small-angle neutron scattering study of Triton X-100-solubilized resting alpha(IIb)beta(3), while new electron microscopy evidence of nanodiscs-embedded alpha(IIb)beta(3) supports the bent/closed resting form. However, only an extended/closed model matches well the hydrodynamics of either octyl-glucoside-solubilized or nanodiscs embedded resting alpha(IIb)beta(3), suggesting that different solubilization strategies and substrate interactions might operate a conformational selection between alternative, stable states. Furthermore, extended/open models are required to match the electron tomography map and the hydrodynamics following the priming-induced beta(3) hybrid domain swing-out, but without immediate full tail separation. Importantly, both extension and opening transitions can occur by pivoting at the recently identified beta(3) hinge point, which does not appear to be freely flexible. The structure and mechanism of action of integrins thus seem to depend on discrete transitions and to be more tightly coupled to the local environment than previously thought. PMID- 20584075 TI - Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites. AB - A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria model Plasmodium chabaudi, we found that low-dose chemotherapy did reduce competitive release. A higher drug dose regimen exerted stronger positive selection on resistant parasites for no detectable clinical gain. We estimated instantaneous selection coefficients throughout the course of replicate infections to analyze the temporal pattern of the strength and direction of within-host selection. The strength of selection on resistance varied through the course of infections, even in untreated infections, but increased immediately following drug treatment, particularly in the high-dose groups. Resistance remained under positive selection for much longer than expected from the half life of the drug. Although there are many differences between mice and people, our data do raise the question whether the aggressive treatment regimens aimed at complete parasite clearance are the best resistance management strategies for humans. PMID- 20584078 TI - TOMOCOMD-CAMPS and protein bilinear indices--novel bio-macromolecular descriptors for protein research: I. Predicting protein stability effects of a complete set of alanine substitutions in the Arc repressor. AB - Descriptors calculated from a specific representation scheme encode only one part of the chemical information. For this reason, there is a need to construct novel graphical representations of proteins and novel protein descriptors that can provide new information about the structure of proteins. Here, a new set of protein descriptors based on computation of bilinear maps is presented. This novel approach to biomacromolecular design is relevant for QSPR studies on proteins. Protein bilinear indices are calculated from the kth power of nonstochastic and stochastic graph-theoretic electronic-contact matrices, M(m)(k) and (s)M(m)(k), respectively. That is to say, the kth nonstochastic and stochastic protein bilinear indices are calculated using M(m)(k) and (s)M(m)(k) as matrix operators of bilinear transformations. Moreover, biochemical information is codified by using different pair combinations of amino acid properties as weightings. Classification models based on a protein bilinear descriptor that discriminate between Arc mutants of stability similar or inferior to the wild-type form were developed. These equations permitted the correct classification of more than 90% of the mutants in training and test sets, respectively. To predict t(m) and Delta DeltaG(f)(o) values for Arc mutants, multiple linear regression and piecewise linear regression models were developed. The multiple linear regression models obtained accounted for 83% of the variance of the experimental t(m). Statistics calculated from internal and external validation procedures demonstrated robustness, stability and suitable power ability for all models. The results achieved demonstrate the ability of protein bilinear indices to encode biochemical information related to those structural changes significantly influencing the Arc repressor stability when punctual mutations are induced. PMID- 20584079 TI - In vitro effect of branch extracts of Juniperus species from Turkey on Staphylococcus aureus biofilm. AB - Methanol and aqueous branch extracts of five Juniperus species were examined for their effects on Staphylococcus aureus ATCC 6538P and S. aureus 810 biofilm. The Turkish plant material was Juniperus communis L. var. communis, J. communis L. var. saxatilis Pall., Juniperus drupacea Labill., Juniperus oxycedrus L. ssp. oxycedrus, J. oxycedrus L. ssp. macrocarpa (Sibth. & Sm.) Ball. The Juniperus extracts were subjected to preliminary phytochemical analysis by thin-layer chromatography. The antimicrobial activity was evaluated using the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The effects of the extracts on biofilm formation and preformed biofilm were quantified by both biomass OD and the CFU counting method. The phytochemical screening revealed the presence of polyphenols, coumarins, lignans, steroids, alkaloids and terpenes. For both strains, the MICs of all extracts were in the range of 4.88-78.12 microg mL(-1). On S. aureus ATCC 6538P, the effects of subinhibitory concentration (0.5 MIC) of the extracts were minimal on planktonic growth and on adhering cells, whereas they were greater on biofilm formation. Differently, on S. aureus 810, they showed only a rather low efficacy on biofilm formation. The extracts at 2 MIC demonstrated a good activity on a preformed biofilm of S. aureus ATCC 6538P. PMID- 20584080 TI - Characterization of a lipopolysaccharide mutant of Leptospira derived by growth in the presence of an anti-lipopolysaccharide monoclonal antibody. AB - A lipopolysaccharide mutant of Leptospira interrogans (LaiMut) was obtained by growth in the presence of an agglutinating monoclonal antibody (mAb) against lipopolysaccharide. Agglutination reactions with anti-lipopolysaccharide mAbs and polyclonal antibodies showed that LaiMut had lost some serogroup Icterohaemorrhagiae agglutinating epitopes. However, LaiMut displayed an increased reactivity to antisera against related serogroups, suggesting that the disruption of some lipopolysaccharide epitopes resulted in greater exposure to cross-reactive epitopes, not accessible to antibodies in the wild type (LaiWT). Comparison of the nucleotide sequences of the lipopolysaccharide loci of LaiMut and Lai wild type (LaiWT) strains showed an inframe stop mutation in the gene encoding undecaprenyl-galactosyltransferase, a protein that provides a fundamental and nonredundant function essential for lipopolysaccharide biosynthesis. Despite this, the biosynthesis of lipopolysaccharide agglutinating antigens was not abolished by the mutation. Based on the phenotype of LaiMut and analysis of the domain structure of the undecaprenyl-galactosyltransferase in relation to the mutation, we propose that the mutation results in the expression of two functional proteins in place of the undecaprenyl-galactosyltransferase. We hypothesize that the loss of coordination of the coupled function afforded by the intact dual function protein present in the parent strain results in an inefficient production of lipopolysaccharide in LaiMut. PMID- 20584081 TI - New plasmids and putative virulence factors from the draft genome of an Australian clinical isolate of Photorhabdus asymbiotica. AB - Clinical isolates of Photorhabdus asymbiotica have been recovered from patients in both the United States of America and Australia, and the full sequence of P. asymbiotica ATCC43949 from the United States has been reported recently. In contrast to other bacteria in the genus that only infect insects, P. asymbiotica strains are able to infect both insects and humans. Using a combination of Solexa (Illumina) and 454 Life Sciences (Roche) sequence data in different assembly pipelines, we report on a draft genome sequence of a strain of P. asymbiotica recovered from a patient from Kingscliff, Australia. The best assembly yielded an N50 scaffold size of 288 627 base pairs (bp) with >88.6% of the predicted genome covered by scaffolds over 100 000 bp. One of the central differences found between this Australian isolate and the US isolate is the presence of an additional plasmid, pPAA3. This plasmid is similar to pCRY from Yersinia pestis, the causative agent of bubonic plague, and the presence of pPAA3 may account for the increased virulence of Australian isolates both against tissue culture cells and infected patients. The genome of the Kingscliff strain also contains several genomic differences from the US isolate, whose potential significance in virulence against both humans and insects is discussed. PMID- 20584082 TI - Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea. AB - The tripartite ATP-independent periplasmic (TRAP) transporters are the best studied family of substrate-binding protein (SBP)-dependent secondary transporters and are ubiquitous in prokaryotes, but absent from eukaryotes. They are comprised of an SBP of the DctP or TAXI families and two integral membrane proteins of unequal sizes that form the DctQ and DctM protein families, respectively. The SBP component has a structure comprised of two domains connected by a hinge that closes upon substrate binding. In DctP-TRAP transporters, substrate binding is mediated through a conserved and specific arginine/carboxylate interaction in the SBP. While the SBP component has now been relatively well characterized, the membrane components of TRAP transporters are still poorly understood both in terms of their structure and function. We review the expanding repertoire of substrates and physiological roles for experimentally characterized TRAP transporters in bacteria and discuss mechanistic aspects of these transporters using data primarily from the sialic acid-specific TRAP transporter SiaPQM from Haemophilus influenzae, which suggest that TRAP transporters are high-affinity, Na(+)-dependent unidirectional secondary transporters. PMID- 20584083 TI - Differential adaptation of microbial pathogens to airways of patients with cystic fibrosis and chronic obstructive pulmonary disease. AB - Cystic fibrosis (CF), the most common autosomal recessive disorder in Caucasians, and chronic obstructive pulmonary disease (COPD), a disease of adults, are characterized by chronic lung inflammation, airflow obstruction and extensive tissue remodelling, which have a major impact on patients' morbidity and mortality. Airway inflammation is stimulated in CF by chronic bacterial infections and in COPD by environmental stimuli, particularly from smoking. Pseudomonas aeruginosa is the major bacterial pathogen in CF, while in COPD, Haemophilus influenzae is most frequently observed. Molecular studies indicate that during chronic pulmonary infection, P. aeruginosa clones genotypically and phenotypically adapt to the CF niche, resulting in a highly diverse bacterial community that is difficult to eradicate therapeutically. Pseudomonas aeruginosa clones from COPD patients remain within the airways only for limited time periods, do not adapt and are easily eradicated. However, in a subgroup of severely ill COPD patients, P. aeruginosa clones similar to those in CF persist. In this review, we will discuss the pathophysiology of lung disease in CF and COPD, the complex genotypic and phenotypic adaptation processes of the opportunistic bacterial pathogens and novel treatment options. PMID- 20584084 TI - Biochemical characterization of an ecto-ATP diphosphohydrolase activity in Candida parapsilosis and its possible role in adenosine acquisition and pathogenesis. AB - In this work, we describe the ability of intact cells of Candida parapsilosis to hydrolyze extracellular ATP. ATP hydrolysis was stimulated by MgCl(2) in a dose dependent manner. The ecto-ATPase activity was increased in the presence of 5 mM MgCl(2), with values of V(max) and apparent K(m) for Mg-ATP(2-) increasing to 33.80 +/- 1.2 nmol Pi h(-1) 10(-8) cells and 0.6 +/- 0.06 mM, respectively. Inhibitors of phosphatases, mitochondrial Mg(2+)-ATPases and Na(+)-ATPases had no effect on the C. parapsilosis Mg(2+)-stimulated ATPase activity, but extracellular impermeant compounds, 4,4'-diisothiocyanatostilbene-2,2'disulfonic acid and suramin, reduced enzyme activity in yeast living cells by 83.1% and 81.9%, respectively. ARL 67156 (6-N,N'-diethyl-d-beta-gamma-dibromomethylene ATP), a nucleotide analogue, also inhibited the ecto-ATPase activity in a dose dependent manner. ATP was the best substrate for the yeast Mg(2+)-stimulated ecto enzyme, but ADP, ITP, CTP, GTP and UTP were also hydrolyzed. A direct relationship between ecto-ATPase activity and adhesion to host cells was observed. In these assays, inhibition of enzyme activity resulted in decreased levels of yeast adhesion to epithelial cells. Based also on the differential expression of ecto-ATPase activities in the different isolates of C. parapsilosis, the possible role of this enzyme in fungal biology is discussed. PMID- 20584085 TI - The impact of menstrual disorders on quality of life in women with inherited bleeding disorders. AB - SUMMARY: Menorrhagia, heavy menstrual bleeding, is a common condition that has a substantial impact on the lives of many women. The objective measurement of menorrhagia is often impractical; therefore diagnosis and treatment are usually based on the direct perception of the woman. Menstrual problems are likely to be worse in women with bleeding disorders, as they are more likely to have heavy and painful menstrual periods and ovulation bleeding and pain. These can have a major impact on the quality of women's lives, especially those who suffer heavy menstruation. These problems can also lead to limitations at work and school and hinder educational and academic achievements. Only few studies describe how quality of life (QOL) changes in women with an underlying haemostatic defect; poorer QOL being associated with more frequent bleeding symptoms. Early recognition, accurate diagnosis and appropriate management of bleeding disorders should improve not only the quality of care for affected women but also their QOL. Increased awareness of the high prevalence of menstrual problems especially menorrhagia is essential for early diagnosis and provision of appropriate treatments without any delay. Accurate knowledge of the impact of menorrhagia on health-related quality of life (HRQOL) and its adequate assessment help individualize treatment and assess the magnitude of changes in HRQOL. An ideal situation would be to use a generic and a disease-specific measure together so that comparisons can be made on a general and disease-specific level. PMID- 20584086 TI - Perspectives from the frontlines: palliative care providers' expectations of Canada's compassionate care benefit programme. AB - Recognising their valuable role as key informants, this study examines the perspectives of front-line palliative care providers (FLPCP) regarding a social benefit programme in Canada designed to support family caregivers at end-of-life, namely the Compassionate Care Benefit (CCB). The CCB's purpose is to provide income assistance and job security to family caregivers who take temporary leave from employment to care for a dying family member. Contributing to an evaluative study that aims to provide policy-relevant recommendations about the CCB, this analysis draws on semi-structured interviews undertaken in 2007/2008 with FLPCPs (n = 50) from across Canada. Although participants were not explicitly asked during interviews about their expectations of the CCB, thematic content analysis revealed 'expectations' as a key finding. Through participants' discussions of their knowledge of and familiarity with the CCB, specific expectations were identified and grouped into four categories: (1) temporal; (2) financial; (3) informational; and (4) administrative. Findings demonstrate that participants expect the CCB to provide: (1) an adequate length of leave time from work, which is reflective of the uncertain nature of caregiving at end-of-life; (2) adequate financial support; (3) information on the programme to be disseminated to FLPCPs so that they may share it with others; and (4) a simple, clear, and quick application process. FLPCPs hold unique expertise, and ultimately the power to shape uptake of the CCB. As such, their expectations of the CCB contribute valuable knowledge from which relevant policy recommendations can be made to better meet the needs of family caregivers and FLPCPs alike. PMID- 20584087 TI - Selling your self? The psychological impact of street sex work and factors affecting support seeking. AB - Previous research investigating the risks of female street sex work has tended to focus on the most tangible risks to physical health and safety. This is reflected in the provision of support services for sex workers, where these aspects are prioritised. There is little research focusing solely on the psychological risks of sex work. This qualitative study aimed to explore the perceived psychological impact of street sex work and factors that affected support seeking. Interviews were carried out with a sample of UK female street sex workers (n = 7) who attended a drop-in clinic and health professionals (n = 5) who provided input to the drop-in service. The analytic process, which drew from an interpretative phenomenological approach, revealed four main themes that work together to describe the emotional impact of selling sex. Implications for support services and future research are highlighted. PMID- 20584088 TI - Self-care and cystic fibrosis: a review of research with adults. AB - The issue of self-care is becoming increasingly central to both policy and practice in health and social care in the community. It is imperative therefore that research in this important area is drawn together and presented coherently so as to ensure that change can be informed by evidence and implemented sensitively. As cystic fibrosis (CF) has until recently been regarded as a paediatric condition, there is relatively little research that focuses on the self-care of adults. Although not entirely uncritical of traditional biomedicine, these studies focus on individual patient deficits and are directed primarily at facilitating their 'compliance'. After discussing some important methodological, evidential and theoretical limitations of this research, other recent CF literature will be considered that suggests the possibility of developing a 'social model' for self-care research. The proposed model is more pluralistic and less prescriptive than its predecessors and the resulting 'types' of self-care indicate that both old and new, mainstream and marginal discourses should co exist. Indeed, recognising the legitimacy of distinct varieties of self-care not only guards against unwarranted moralising and pathologising but may also enable self-care support to be negotiated and tailored more appropriately. PMID- 20584089 TI - Image analysis as an adjunct to manual HER-2 immunohistochemical review: a diagnostic tool to standardize interpretation. AB - AIMS: Accurate determination of HER-2 status is critical to identify patients for whom trastuzumab treatment will be of benefit. Although the recommended primary method of evaluation is immunohistochemistry, numerous reports of variability in interpretation have raised uncertainty about the reliability of results. Recent guidelines have suggested that image analysis could be an effective tool for achieving consistent interpretation, and this study aimed to assess whether this technology has potential as a diagnostic support tool. METHODS AND RESULTS: Across a cohort of 275 cases, image analysis could accurately classify HER-2 status, with 91% agreement between computer-aided classification and the pathology review. Assessment of the continuity of membranous immunoreactivity in addition to intensity of reactivity was critical to distinguish between negative and equivocal cases and enabled image analysis to report a lower referral rate of cases for confirmatory fluorescence in situ hybridization (FISH) testing. An excellent concordance rate of 95% was observed between FISH and the automated review across 136 informative cases. CONCLUSIONS: This study has validated that image analysis can robustly and accurately evaluate HER-2 status in immunohistochemically stained tissue. Based on these findings, image analysis has great potential as a diagnostic support tool for pathologists and biomedical scientists, and may significantly improve the standardization of HER-2 testing by providing a quantitative reference method for interpretation. PMID- 20584090 TI - Secondary vascular changes in pulmonary sequestrations. AB - AIMS: Whilst parenchymal changes in pulmonary sequestrations are well described, there are comparatively little data on associated vascular changes and their extent. The aim of this study was to retrospectively review morphological changes within sequestrations, concentrating on vascular changes and associations with clinical parameters. METHODS AND RESULTS: Twenty-seven resected cases of sequestrations (intralobar n = 20, extralobar n = 7) showed a male predominance (n = 16) and an age range of 2 months-60 years (average 13 years). Plexogenic vascular changes (medial hypertrophy and intimal fibrosis) were seen in 15 of 27 cases, as well as plexiform lesions in seven cases. Patients with plexogenic changes had a higher mean age compared with those lacking vascular changes (19 versus 6 years) and were more commonly female. Respiratory tract infections were associated solely with intralobar sequestrations. No other associations between presenting symptoms and histopathological parameters were identified. Adjacent lung showed lesser plexogenic changes in six of 22 intralobar cases. There were features of type 2 congenital cystic adenomatoid lesions in 63% of cases. Dissection of the supplying systemic artery (n = 1), intralesional aspergilloma (n = 1) and coexistent lymphangiomatosis (n = 1) were also identified. CONCLUSIONS: Hypertensive vascular changes are not uncommon in both intrapulmonary and extrapulmonary sequestrations, although their relative severity seems unrelated to presenting symptoms. PMID- 20584092 TI - Dietary antioxidants improve arteriogenic erectile dysfunction. AB - Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de endothelialization of the iliac arteries. Ballooned and age-matched control animals were assigned into subgroups receiving pomegranate extract antioxidants in drinking water or tap water as placebo. After 8 weeks, penile blood flow and erectile activity were recorded. Erectile tissue relaxation, oxidative products, oxidative stress-responsive genes and structure were examined using organ bath, enzyme immunoassay, quantitative real-time polymerase chain reaction and transmission electron microscopy, respectively. Arterial ballooning caused diffused atherosclerosis, decreased intracavernosal blood flow and led to ED. Impairment of endothelium-dependent relaxation, diffused fibrosis, increased oxidative products, upregulation of superoxide dismutase (SOD) and aldose reductase (AR) gene expression, mitochondrial and endothelial structural damage and increased caveolae were evident in erectile tissues from atherosclerotic animals receiving placebo. Upregulation of antioxidant enzymes SOD and AR failed to protect ischaemic erectile tissue from oxidative injury. Pomegranate extract significantly improved intracavernosal blood flow, erectile activity, smooth muscle relaxation and fibrosis of the atherosclerotic group in comparison with the atherosclerotic group receiving placebo, but did not normalize them to the age-matched control levels. Pomegranate extract appeared more effective in diminishing oxidative products, preventing SOD and AR gene upregulation, and protecting mitochondrial, endothelial and caveolae structural integrity of the atherosclerotic group. Our data suggest the presence of oxidative stress in ED and a more efficient action of antioxidants on molecular and ultrastructural alterations than on distinct functional deficit and structural damage in the ischaemic penis. PMID- 20584091 TI - Evaluation of glomerular filtration rate in HIV-1-infected patients before and after combined antiretroviral therapy exposure. AB - BACKGROUND: The prevalence and factors associated with an increased risk of renal dysfunction in HIV-infected patients receiving or not receiving antiretroviral therapy (ART) have been poorly evaluated in observational settings. METHODS: Patients in the ICONA Foundation cohort with at least two creatinine values available while still ART-naive were enrolled in the study. A logistic regression analysis was performed to identify predictors of an estimated glomerular filtration rate (eGFR)<90 mL/min/1.73 m(2) at baseline. The incidence and predictors of a >20% reduction in eGFR from pre-combination ART (cART) levels (or a decrease from >=90 to <90 mL/min/1.73 m(2) ) were evaluated by Poisson regression. RESULTS: A total of 1505 patients were included in the study; 363 (24%) had eGFR<90 mL/min/1.73 m(2) at baseline. Older patients [odds ratio (OR) 1.58 per 10 years older; P<0.00001], female patients (OR 2.41 vs. male patients; P<0.00001), those who had diabetes and/or hypertension (OR 2.36 vs. neither; P<0.03) and patients with higher baseline CD4 count (OR 1.06 per 100 cells/MUL higher; P<0.03) showed a greater risk of eGFR<90 mL/min/1.73 m(2) . Ninety-six patients experienced an eGFR decrease of >20% from pre-cART levels (6.8 per 100 person-years). Older age [relative risk (RR) 1.41 per 10 years older; P=0.005], female gender (RR 2.25 vs. male; P=0.003) and current exposure to didanosine (ddI), tenofovir and protease inhibitors were the major determinants. CONCLUSIONS: We observed a relatively high rate of mild renal dysfunction in the absence of ART. In addition to traditional risk factors such as older age and diabetes/hypertension, female gender and current use of ddI, tenofovir and protease inhibitors were associated with a greater risk of decreased renal function as measured by eGFR. PMID- 20584093 TI - Characterization of dendritic cells in testicular draining lymph nodes in a rat model of experimental autoimmune orchitis. AB - The maturation state of dendritic cells (DC) is regarded as a control point for the induction of peripheral tolerance or autoimmunity. Experimental autoimmune orchitis (EAO) serves as a model to investigate inflammatory-based testicular impairment, which ranks as a significant cause of male infertility. This work aimed to determine whether DC enrichment occurs organotypically in testicular draining lymph nodes (TLN) compared with LN draining the site of immunization (ILN) and thus contributes to the pathogenesis of autoimmune orchitis. In this regard, we quantified and characterized the DC from TLN and ILN in rats with EAO. Flow cytometric analysis showed a significant increase in the percentage of DC (OX62+) only in TLN from EAO rats compared with normal (N) and adjuvant control (C) groups. The number of DC from ILN and TLN expressing CD80, CD86 and major histocompatibility complex (MHC) II was comparable among N, C and experimental (E) groups at 30 and 50 days after the first immunization. However, TLN DC from EAO rats (50 days) showed an increase in mean fluorescence intensity for MHC II compared with N, C and E groups (30 days). The mRNA expression level of IL-10 and IL-12p35 was significantly upregulated in enriched DC fraction from TLN in EAO rats with no significant changes observed in ILN DC. The expression of IL-23p19 mRNA remained unchanged. Functional data, using proliferation assays showed that EAO-DC from TLN, but not from ILN, significantly enhanced the proliferation of naive T cells compared with C-DC. In summary, our data suggest that the DC in TLN from orchitis rats are mature, present antigens to T cells and stimulate an autoimmune response against testicular antigens, thus causing immunological infertility. PMID- 20584095 TI - Empirical evidence of senescence in adult damselflies (Odonata: Zygoptera). AB - 1. Age-dependent increases in mortality have been documented in a variety of species of insect under laboratory conditions. However, while strong statistical evidence has been presented for senescence in vertebrate populations in the wild, we know little about the rate and shape of senescence in wild populations of insects. 2. Odonates (damselflies and dragonflies) provide excellent candidate species for evaluating demographic senescence as they are large enough to be marked individually and they are easily re-sighted without recapture. The prevailing opinion - based entirely on qualitative examination of the declines in log numbers alive with time since marking - is that odonates exhibit age independent daily survivorship. 3. Here, we examine mark-recapture data on the Azure Damselfly Coenagrion puella over two consecutive seasons. For the first time, we evaluate and compare the fit of quantitative models that not only account for weather-dependent daily variation in daily re-sighting rates, but also age-dependent variation in daily survivorship. 4. Models with age-dependent declines in daily survivorship provide a more parsimonious explanation for the data than similar models without these age-dependent effects. In general, models in which mortality increases in an exponential (Gompertz) fashion explain the mark-recapture sequences more efficiently than a range of alternative models, including those in which mortality increases as a power function (Weibull) or reaches a plateau (logistic). These results are indicative of a general senescent decline in physiological functioning, which is particularly marked after 15 days as a mature adult. 5. Weather (temperature, sun and precipitation) and initial mite load influenced the probability of daily re-sighting. Weather and mite load also influenced daily survivorship, but their effects differed between seasons. 6. Overall, fitting models with age as an explicit covariate demonstrates that odonates do indeed senesce. This contradicts previously held assumptions that Odonata do not exhibit age-dependent survivorship in the wild. PMID- 20584094 TI - The mechanical function of the periodontal ligament in the macaque mandible: a validation and sensitivity study using finite element analysis. AB - Whilst the periodontal ligament (PDL) acts as an attachment tissue between bone and tooth, hypotheses regarding the role of the PDL as a hydrodynamic damping mechanism during intraoral food processing have highlighted its potential importance in finite element (FE) analysis. Although experimental and constitutive models have correlated the mechanical function of the PDL tissue with its anisotropic, heterogeneous, viscoelastic and non-linear elastic nature, in many FE simulations the PDL is either present or absent, and when present is variably modelled. In addition, the small space the PDL occupies and the inability to visualize the PDL tissue using MUCT scans poses issues during FE model construction and so protocols for the PDL thickness also vary. In this paper we initially test and validate the sensitivity of an FE model of a macaque mandible to variations in the Young's modulus and the thickness of the PDL tissue. We then tested the validity of the FE models by carrying out experimental strain measurements on the same mandible in the laboratory using laser speckle interferometry. These strain measurements matched the FE predictions very closely, providing confidence that material properties and PDL thickness were suitably defined. The FE strain results across the mandible are generally insensitive to the absence and variably modelled PDL tissue. Differences are only found in the alveolar region adjacent to the socket of the loaded tooth. The results indicate that the effect of the PDL on strain distribution and/or absorption is restricted locally to the alveolar bone surrounding the teeth and does not affect other regions of the mandible. PMID- 20584096 TI - Local exposure shapes spatial patterns in infectivity and community structure of Daphnia parasites. AB - 1. Spatial patterns in parasite community structure are probably driven by the availability of infectious stages. This is because hosts become infected through picking up infectious stages from their environment. Several studies have, however, reported strong genotype by genotype interactions and parasite-mediated selection in hosts. This leads to the prediction of a parasite by host population interaction with respect to infection rates and intensities, which may also shape spatial patterns in parasite community structure. 2. Using the water flea Daphnia magna and its microparasites as a model, we carried out a laboratory experiment to test explicitly to what extent parasite community structure in host populations is determined by the availability of infectious stages in the sediment they are exposed to, and to what extent host population identity and location play a role. 3. We exposed 10 D. magna host populations each to sediment of their own habitat and sediment of the other nine habitats, and monitored the parasite community of the resulting experimental populations. 4. Sediment seems to be a strong determinant of parasite infection rates, while there was no overall effect of host population. Sympatric parasite and host population combinations did in most cases not result in significantly different infection rates than allopatric parasite and host combinations. Our results indicate that spore availability could be the key variable determining parasite community structure in natural Daphnia populations. PMID- 20584097 TI - Food-web composition affects cross-ecosystem interactions and subsidies. AB - 1. Ecosystems may affect each other through trophic interactions that cross ecosystem boundaries as well as via the transfer of subsidies, but these effects can vary depending on the identity of species involved in the interaction. 2. In this study, we manipulated two terrestrial bromeliad-living spider species (Aglaoctenus castaneus, Corinna gr. rubripes) that have variable hunting modes, to test their individual and combined effects on aquatic invertebrate community structure and ecosystem processes (i.e. decomposition rate and nitrogen cycling). We predicted that these terrestrial predators can affect aquatic invertebrates and nutrient dynamics within water-filled bromeliads. 3. Aglaoctenus spiders reduced the richness, abundance and biomass of aquatic insect larvae via consumptive or non-consumptive effects on ovipositing terrestrial adults, but effects of the two spider species in combination were usually the linear average of their monoculture effects. In contrast, invertebrates with entirely aquatic life cycles were unaffected or facilitated by spiders. Spiders did not affect either net detritivore biomass or the flux of detrital nitrogen to the bromeliad. Instead, Corinna spiders contributed allochthonous nitrogen to bromeliads. 4. Our results provide the novel observations that predators in one ecosystem not only directly reduce taxa whose life cycles cross-ecosystem boundaries, but also indirectly facilitate taxa whose life cycles are entirely within the second ecosystem. This compensatory response between cross-ecosystem and within ecosystem taxa may have led to an attenuation of top-down effects across ecosystem boundaries. In addition, our results add to a growing consensus that species identity is an important determinant of community structure and ecosystem functioning. Thus, the composition of both terrestrial and aquatic food webs may affect the strength of cross-ecosystem interactions. PMID- 20584098 TI - Prey dispersal rate affects prey species composition and trait diversity in response to multiple predators in metacommunities. AB - 1. Recent studies indicate that large-scale spatial processes can alter local community structuring mechanisms to determine local and regional assemblages of predators and their prey. In metacommunities, this may occur when the functional diversity represented in the regional predator species pool interacts with the rate of prey dispersal among local communities to affect prey species diversity and trait composition at multiple scales. 2. Here, we test for effects of prey dispersal rate and spatially and temporally heterogeneous predation from functionally dissimilar predators on prey structure in pond mesocosm metacommunities. An experimental metacommunity consisted of three pond mesocosm communities supporting two differentially size-selective invertebrate predators and their zooplankton prey. In each metacommunity, two communities maintained constant predation and supported either Gyrinus sp. (Coleoptera) or Notonecta ungulata (Hemiptera) predators generating a spatial prey refuge while the third community supported alternating predation from Gyrinus sp. and N. ungulata generating a temporal prey refuge. Mesocosm metacommunities were connected at either low (0.7% day(-1)) or high (10% day(-1)) planktonic prey dispersal. The diversity, composition and body size of zooplankton prey were measured at local and regional (metacommunity) scales. 3. Metacommunities experiencing the low prey dispersal rate supported the greatest regional prey species diversity (H') and evenness (J'). Neither dispersal rate nor predation regime affected local prey diversity or evenness. The spatial prey refuge at low dispersal maintained the largest difference in species composition and body size diversity between communities under Gyrinus and Notonecta predation, suggesting that species sorting was operating at the low dispersal rate. There was no effect of dispersal rate on species diversity or body size distribution in the temporal prey refuge. 4. The frequency distribution, but not the range, of prey body sizes within communities depended upon prey dispersal rate and predator identity. Taken together, these results demonstrate that prey dispersal rate can moderate the strength of predation to influence prey species diversity and the local frequency distribution of prey traits in metacommunities supporting ecologically different predators. PMID- 20584099 TI - Isolation and characterization of new poly(3HB)-accumulating star-shaped cell aggregates-forming thermophilic bacteria. AB - AIMS: This study aimed at isolating thermophilic bacteria that utilize cheap carbon substrates for the economically feasible production of poly(3 hydroxybutyrate), poly(3HB), at elevated temperatures. METHODS AND RESULTS: Thermophilic bacteria were enriched from an aerobic organic waste treatment plant in Germany, and from hot springs in Egypt. Using the viable colony staining method for hydrophobic cellular inclusions with Nile red in mineral salts medium (MSM) containing different carbon sources, six Gram-negative bacteria were isolated. Under the cultivation conditions used in this study, strains MW9, MW11, MW12, MW13 and MW14 formed stable star-shaped cell-aggregates (SSCAs) during growth; only strain MW10 consisted of free-living rod-shaped cells. The phylogenetic relationships of the strains as derived from 16S rRNA gene sequence comparisons revealed them as members of the Alphaproteobacteria. The 16S rRNA gene sequences of the isolates were very similar (>99% similarity) and exhibited similarities ranging from 93 to 99% with the most closely related species that were Chelatococcus daeguensis, Chelatococcus sambhunathii,Chelatococcus asaccharovorans, Bosea minatitlanensis, Bosea thiooxidans and Methylobacterium lusitanum. Strains MW9, MW10, MW13 and MW14 grew optimally in MSM with glucose, whereas strains MW11 and MW12 preferred glycerol as sole carbon source for growth and poly(3HB) accumulation. The highest cell density and highest poly(3HB) content attained were 4.8g l(-l) (cell dry weight) and 73% (w/w), respectively. Cells of all strains grew at temperatures between 37 and 55 degrees C with the optimum growth at 50 degrees C. CONCLUSIONS: New PHA-accumulating thermophilic bacterial strains were isolated and characterized to produce poly(3HB) from glucose or glycerol in MSM at 50 degrees C. SSCAs formation was reported during growth. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this is the first report on the formation of SSCAs by PHA-accumulating bacteria and also by thermophilic bacteria. PHA-producing thermophiles can significantly reduce the costs of fermentative PHA production. PMID- 20584100 TI - Trajectories of antisocial behaviour towards siblings predict antisocial behaviour towards peers. AB - BACKGROUND: Young siblings' antisocial behaviour is common yet its impact has received relatively little research attention. METHODS: We examined trajectories of antisocial behaviour for a socially diverse sample (n = 99, 58 boys and 41 girls) who were filmed with their older siblings (52 boys and 47 girls) at ages 3 and 6 and with unfamiliar peers at age 6. Latent growth models were used to analyse three indicators of antisocial behaviour (refusal to share/interact, bullying and harming). RESULTS: The average trajectory of antisocial behaviour towards siblings was stable and particularly high for boys with brothers and for children of mothers with no educational qualifications. Sustained and escalating antisocial behaviours towards siblings predicted bullying and refusals to share/interact with unfamiliar peers, independent of associations with concurrent antisocial behaviour towards sibling. CONCLUSIONS: These findings highlight the importance of a developmental perspective when examining antisocial behaviour between young siblings. PMID- 20584101 TI - Reversible autism among congenitally blind children? A controlled follow-up study. AB - BACKGROUND: Atypical forms of autism may yield insights into the development and nature of the syndrome. METHODS: We conducted a follow-up study of nine congenitally blind and seven sighted children who, eight years earlier, had satisfied formal diagnostic criteria for autism and had been included in groups matched for chronological age and verbal ability. In keeping with the original study, we met with teachers to discuss a DSM-based checklist of clinical features of autism, and conducted direct observations of the children to complete assessments on the Childhood Autism Rating Scale (CARS; Schopler, Reichler, and Renner, 1986) and the Behavior Checklist for Disordered Preschoolers (BCDP; Sherman, Shapiro, & Glassman, 1983). RESULTS: As predicted, a substantially higher proportion of blind (eight out of nine) than sighted (none out of seven) children now failed to meet formal DSM criteria for autism, and in keeping with BCDP ratings, they had significantly lower CARS scores. CONCLUSIONS: Follow-up of nine congenitally blind children with autism revealed that, in adolescence, only one still satisfied diagnostic criteria for the syndrome. We consider the implications for theoretical perspectives on the development of autism. PMID- 20584102 TI - A light and scanning electron microscopic study of the closing apparatus in tintinnid ciliates (Ciliophora, Spirotricha, Tintinnina): a forgotten synapomorphy. AB - A membranous closing apparatus shuts the lorica opening in disturbed tintinnids of six genera belonging to four families. The homology of the apparatuses is investigated, using data from the literature and Mediterranean tintinnids studied in vivo and by scanning electron microscopy. Morphological and functional similarities indicate that the foldable closing apparatus is not only a synapomorphy of the genera Codonella (Codonellidae) and Dictyocysta (Dictyocystidae), as suggested 80 years ago, but also of Codonaria (Codonellidae) and Codonellopsis (Codonellopsidae). In Codonaria, Codonella, and Dictyocysta, the apparatuses merge posteriorly into membranous lorica sacs, which probably represent homologous structures. The diagnoses of these genera are improved according to the new findings. The close relationship of Codonella, Codonellopsis, and Dictyocysta is also inferred from small subunit rRNA phylogenies and the ultrastructure of the capsules. It contradicts the current lorica-based classification of the tintinnids. The assumption that the diaphragm like apparatus in the genera Salpingacantha and Salpingella is not homologous to the foldable ones in the genera mentioned above is supported by molecular and cytological features. PMID- 20584103 TI - Strain-dependent serotonin neuron feedback control: role of serotonin 2C receptors. AB - We investigated the role of serotonin(2C) receptor-mediated feedback mechanisms in the response to citalopram in C57BL/6 and DBA/2 mice, which are respectively responders and non-responders to selective serotonin reuptake inhibitors in the forced swimming test. The microdialysis technique was used to assess changes in extracellular serotonin and GABA in the mouse dorsal raphe (DR). Citalopram (1.25 20 mg/kg) raised extracellular serotonin and GABA in the DR of both mouse strains. These effects were abolished by depleting brain serotonin with p chlorophenylalanine (300 mg/kg * 3). Systemic and/or intra-DR infusion of the serotonin(2C) receptor antagonist 6-chloro-5-methyl-1-[[2-[(2-methyl-3 pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline (1 mg/kg and 0.1 MUM, respectively) enhanced citalopram's effect on extracellular serotonin in the DR and medial prefrontal cortex and abolished the rise of GABA in the DR of DBA/2 mice but had no effect in C57BL/6 mice. The serotonin(2C) receptor agonist Ro60-0175 (0.03-3.0 mg/kg) reduced extracellular serotonin and raised GABA in the DR of DBA/2 mice but had much less effect in C57BL/6 mice. These findings show that the sensitivity of serotonin(2C) receptors determines the efficacy of augmentation strategies aimed at enhancing the effect of serotonin reuptake inhibitors on extracellular serotonin through the suppression of serotonin(2C) receptor mediated feedback control of serotonin neurons. PMID- 20584105 TI - In vitro modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity. AB - We have previously shown that all perineuronal nets (PNNs) bearing neurons express a hyaluronan synthase (HAS), a link protein (usually cartilage link protein-1; Crtl1) and a chondroitin sulfate proteoglycan (usually aggrecan). Animal lacking Crtl1 in the CNS lacks normal PNNs. PNNs are implicated in the control of neuronal plasticity, and interventions to modulate PNN formation will be useful for manipulating plasticity. We have developed an in vitro model which demonstrates how the structural components of PNNs trigger their formation, using human embryonic kidney cells, which do not normally produce a pericellular matrix. Expression of HAS3 leads to the production of a diffuse matrix. It was converted into a compact PNN-like structure when the cells also expressed Crtl1 and aggrecan. This matrix was stained by Wisteria floribunda, contained Crtl1 and aggrecan, and like PNNs, could only be solubilized in 6 M urea. In the absence of hyaluronan produced by HAS3, aggrecan and Crtl1 dissipated into the medium, but when the cells were transfected to produce a hyaluronan matrix, Crtl1 and aggrecan were incorporated into it. Cells lacking any one of these molecules showed impaired integrity of the PNNs. Cells expressing HAS3 and Crtl1 were able to incorporate exogenous aggrecan into their pericellular matrix. PMID- 20584104 TI - Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson's disease. AB - Peripheral inflammation could play a role in the origin and development of certain neurodegenerative disorders. To ascertain this possibility, a model of dopaminergic neurodegeneration based on the injection of the inflammatory agent lipopolysaccharide (LPS) within the substantia nigra was assayed in rats with ulcerative colitis (UC) induced by the ingestion of dextran sulphate sodium. We found an increase in the levels of inflammatory markers from serum (tumor necrosis factor-alpha, IL-1beta, IL-6 and the acute phase protein C-reactive protein) and substantia nigra (tumor necrosis factor-alpha, IL-1beta, IL-6, inducible nitric oxide synthase, intercellular adhesion molecule-1, microglial and astroglial populations) of rats with UC, as well as an alteration of the blood-brain barrier permeability and the loss of dopaminergic neurons. UC reinforced the inflammatory and deleterious effects of LPS. On the contrary, clodronate encapsulated in liposomes (ClodLip), which depletes peripheral macrophages, ameliorated the effect of LPS and UC. Peripheral inflammation might represent a risk factor in the development of Parkinson's disease. PMID- 20584106 TI - Activation of GABA-B receptors induced by systemic amphetamine abolishes dopamine release in the rat lateral septum. AB - The lateral septum is a brain nucleus involved in various mental disorders such as anxiety and drug addiction. In the present study, we investigated whether systemic amphetamine, known to release dopamine (DA) in nucleus accumbens, will also release DA in lateral septum. Our results show that systemic amphetamine administration (2 mg/kg i.p.) induced a significant increase in DA extracellular levels in nucleus accumbens but not in lateral septum. Interestingly, intralateral septum perfusion of amphetamine through the microdialysis probe induced a significant increase in DA extracellular levels. To test if GABAergic neurotransmission in lateral septum was responsible for inhibiting the release of DA when amphetamine was administered systemically, we perfused a GABA-B selective antagonist (CGP-52432) intra lateral septum. Systemic amphetamine administration induced a significant increase in lateral septum DA release when CGP-52432 was concomitantly superfused. Our results indicate that the systemic administration of amphetamine induces an increase in lateral septum GABA release and the consequent activation of GABA-B receptors counteracting the direct effect of amphetamine on lateral septum DA release. PMID- 20584107 TI - Co-expression of leptin and oestrogen receptors in the preoptic-hypothalamic area. AB - The interaction between the reproductive axis and energy balance suggests that leptin acts as a possible mediator. This hormone acts in the regulation of metabolism, feeding behaviour and reproduction. Animals homozygous for the gene 'ob' (ob/ob) are obese and infertile, and these effects are reversed after systemic administration of leptin. Thus, the present study aimed to determine: (i) whether cells that express leptin also express oestrogen receptors of type alpha (ER-alpha) or -beta (ER-beta) in the medial preoptic area (MPOA) and in the arcuate (ARC), dorsomedial (DMH) and ventromedial hypothalamic nucleus and (ii) whether there is change in the gene and protein expression of leptin in these brain areas in ovariectomised (OVX) animals when oestrogen-primed. Wistar female rats with normal oestrous cycles or ovariectomised oestrogen-primed or vehicle (oil)-primed were utilised. To determine whether there was a co-expression, immunofluorescence was utilised for double staining. Confocal microscopy was used to confirm the co-expression. The technique of real-time polymerase chain reaction and western blotting were employed to analyse gene and protein expression, respectively. The results obtained showed co-expression of leptin and ER-alpha in the MPOA and in the DMH, as well as leptin and ER-beta in the MPOA, DMH and ARC. However, we did not detect leptin in the MPOA, ARC and DMH using western blotting and there was no statistical difference in leptin gene expression in the MPOA, DMH, ARC, pituitary or adipose tissue between OVX rats treated with oestrogen or vehicle. In conclusion, the results obtained in the present study confirm that the brain is also a source of leptin and reveal co expression of oestrogen receptors and leptin in the same cells from areas related to reproductive function and feeding behaviour. Although these data corroborate the previous evidence obtained concerning the interaction between the action of brain leptin and reproductive function, the physiological relevance of this interaction remains uncertain and additional studies are necessary to elucidate the exact role of central leptin. PMID- 20584108 TI - Evidence for suprachiasmatic vasopressin neurones innervating kisspeptin neurones in the rostral periventricular area of the mouse brain: regulation by oestrogen. AB - In rodents, a circadian signal from the suprachiasmatic nucleus (SCN) is essential for the pro-oestrous surge of gonadotrophin-releasing hormone (GnRH), which, in turn, induces luteinising hormone (LH) surge and ovulation. We hypothesised that kisspeptin (KP) neurones in the anteroventral periventricular and periventricular preoptic nuclei (AVPV/PeN) form part of the communication pathway between the SCN and GnRH neurones. In anterograde track tracing studies, we first identified vasopressin (VP)-containing axons of SCN origin in apposition to KP-immunoreactive (IR) neurones. Studies to quantify this input relied on the observation that VP-synthesising neurones in the SCN differ from other VP systems in their lack of galanin expression. In ovariectomised mice, 30.79 +/- 1.63% of KP-IR perikarya and proximal dendrites within the AVPV/PeN received galanin negative VP-IR varicosities. Oestrogen-treatment significantly increased the number of KP-IR neurones, with their percentage apposed by galanin-negative VP-IR varicosities (46.95 +/- 1.88%) and the number of VP-IR appositions on individual KP-IR neurones. At the ultrastructural level, the VP-IR terminals formed symmetric synapses with KP-IR neurones, which was in accordance with the morphology of inhibitory synapses established by SCN neurones. By contrast to VP, vasoactive intestinal polypeptide (VIP), which is synthesised by a distinct subset of SCN neurones, occurred only rarely in axons apposed to KP-IR neurones. Altogether, our results are consistent with the hypothesis that KP neurones located in the mouse AVPV/PeN receive circadian information from the SCN via a vasopressinergic monosynaptic pathway, which is enhanced by oestrogen. PMID- 20584109 TI - Sleep-related painful erection in a 50-year-old man successfully treated with cinitapride. AB - INTRODUCTION: The sleep-related painful erection (SRPE) is a well-established parasomnia characterized by episodes of penile pain during an erection and typically appears during REM sleep. It is associated with nocturnal awakenings, anxiety, and irritability. AIM: To report a case study that highlights the successful treatment of SRPE with cinitapride. METHODS: We present a case report of a 50-year-old man suffering from SRPE that was studied by polysomnography. RESULTS: Severe fragmentation of rapid eye movement (REM) sleep was observed, and nine episodes of sleep-related erections were observed through the night; they were associated with REM sleep, and five of them were classified as SRPE. Cinitapride before the onset of sleep was started. Both the frequency and intensity of SRPE gradually decreased during a period of 6 months with the maintenance of normal sexual function. CONCLUSION: Cinitapride can play a role in reducing SRPE at night probably due to central modulation of neurotransmitters mediating erection. PMID- 20584110 TI - New enhancements of the scrotal one-incision technique for placement of artificial urinary sphincter allow proximal cuff placement. AB - INTRODUCTION: Urinary incontinence impairs sexual functioning and sexual satisfaction. Traditional artificial urinary sphincter (AUS) implantation requires perineal incision for cuff placement and a second inguinal incision for reservoir and pump placement. We believed AUS could be placed easier and quicker through one scrotal incision. Aim. In an effort to effect more proximal placement of the cuff while keeping the advantages of the one scrotal incision technique, we report enhancements to the original surgical technique. METHODS: Thirty patients have been operated upon using the enhanced technique. A modification of the SKW retractor system (AMS) facilitates deep bulbar exposure. Twenty patients were first time implantations and 10 were revisions with five of the revisions having had the original AUS placed by traditional two-incision technique. Two of the first time AUS patients received an inflatable penile prosthesis through the same incision. MAIN OUTCOME MEASURES: We evaluated site of cuff placement, sizes of cuffs used, postoperative continence status. RESULTS: All of the virgin AUS required dissection of the bulbocavernosus muscle prior to cuff placement. In scrotally placed revisions, replacement cuffs were situated considerably proximal (4.5-7.5 cm) to the original cuff site. The perineal placed revisions were accomplished through a scrotal incision with replacement of two cuffs in the same site and the three other patients immediately distal. No intraoperative complications were seen. One patient developed scrotal hematoma requiring drainage. Only 15 patients are available for follow-up and all are socially continent (one pad or less). CONCLUSIONS: Transscrotal approach is used safely and efficiently for penile implants and AUS implantation. The new enhancements to the one-scrotal incision technique allow more proximal cuff placement as evidenced by the bulbocavernosus muscle dissection and use of larger cuffs. Continence rate is similar to rates achieved with perineal placement of cuff found in the literature. PMID- 20584111 TI - Vasculogenic erectile dysfunction and metabolic syndrome. AB - INTRODUCTION: Erectile dysfunction (ED), defined as the inability to achieve and/or maintain a penile erection sufficient for sexual intercourse, is a health problem affecting more than one-half of men between the age of 40 and 70 years. AIM: The aim of the present study was to determine the potential factors affecting penile vascular flow and predictability of vascular flow in patients with ED. METHODS: Totally 163 male patients between 29 and 82 years of age who were admitted to our outpatient clinic with complaints of ED were included. After a detailed medical history was obtained, all patients were asked to complete the International Index of Erectile Function (IIEF) questionnaire. Blood samples were obtained for measurements of serum cholesterol, triglycerides, and fasting blood glucose (FBG), and the body mass index (BMI) was calculated. MAIN OUTCOME MEASURES: Penile color Doppler ultrasonography (PDU) was performed to evaluate flow patterns, Mann-Whitney U-test and Spearman correlation analyses were used to assess the relationship of PDU findings with hypertension, obesity (BMI >= 25 kg/m(2) ), FBG, and cholesterol levels measurements. RESULTS: The mean age, IIEF score, and BMI of the study population was 51.3 +/- 12.1 years, 11.9 +/- 6.1 and 28.5 +/- 4.0 kg/m(2), respectively. When the vascular pathologies detected with PDU and the presence of risk factors were compared, no significant correlation was determined between arterial insufficiency and metabolic syndrome (MS), whereas there was a significant correlation between veno-occlusive dysfunction and MS. CONCLUSION: The prevalence of ED increases with advanced age and with the presence of a systemic disease. Basic evaluations may not always be sufficient for assessment of ED. In the presence of MS, the use of penile Doppler ultrasonography should be considered for the evaluation of penile vascular structures in ED patients. PMID- 20584112 TI - Disorders of orgasm in women: a literature review of etiology and current treatments. AB - INTRODUCTION: Disorders of orgasm in women, defined as the persistent or recurrent delay in or absence of orgasm, affect up to a quarter of the female population. AIM: To review existing research findings on the etiology and treatments of disorders of orgasm in women to provide a useful reference tool for clinicians who evaluate and treat patients with these conditions. METHODS: PubMed and PsycINFO search for articles published between 1980 and 2009 using the keywords "orgasm*,""anorgasmia," and "female*,""woman," or "women," in addition to "female orgasmic disorder" and "disorders of orgasm in women." MAIN OUTCOME MEASURES: Findings on the etiological factors and effects of a variety of treatment interventions on improving disorders of orgasm in women. Results. Literature on prevalence and causes of disorders of orgasm in women is abundant, yet more reports of successful treatments are needed. Nevertheless, many promising approaches have been suggested, and data support several potential treatments such as bupropion, sildenafil, estrogen, and testosterone among others. CONCLUSIONS: Although more research is needed to better understand and manage disorders of orgasm in women, significant progress is being made. PMID- 20584113 TI - Intracavernous delivery of synthetic angiopoietin-1 protein as a novel therapeutic strategy for erectile dysfunction in the type II diabetic db/db mouse. AB - INTRODUCTION: Patients with erectile dysfunction (ED) associated with type II diabetes often have impaired endothelial function and tend to respond poorly to oral phosphodiesterase type 5 inhibitors. Therefore, neovascularization is a promising strategy for curing diabetic ED. AIM: To determine the effectiveness of a soluble, stable, and potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous angiogenesis and erectile function in a mouse model of type II diabetic ED. Methods. Sixteen-week-old male db/db mice (in which obesity and type II diabetes are caused by a mutation in the leptin receptor) and control C57BL/6J mice were used and divided into four groups (N=14 per group): age-matched controls; db/db mice receiving two successive intracavernous injections of phosphate-buffered saline (PBS) (days -3 and 0; 20 uL); db/db mice receiving a single intracavernous injection of COMP-Ang1 protein (day 0; 5.8 ug/20 uL); and db/db mice receiving two successive intracavernous injections of COMP-Ang1 protein (days -3 and 0; 5.8 ug/20 uL). MAIN OUTCOME MEASURES: Two weeks later, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with antibodies to platelet/endothelial cell adhesion molecule-1 (PECAM-1) (endothelial cell marker), phosphohistone H3 (PH3, a nuclear protein indicative of cell proliferation), phospho-endothelial nitric oxide synthase (eNOS), and eNOS. Penis specimens from a separate group of animals were used for cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) quantification. RESULTS: Local delivery of COMP-Ang1 protein significantly increased eNOS phosphorylation and cGMP and cAMP expression compared with that in the group treated with PBS. Repeated intracavernous injections of COMP-Ang1 protein completely restored erectile function and cavernous endothelial content through enhanced cavernous neoangiogenesis as evaluated by PECAM-1 and PH3 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay, whereas a single injection of COMP-Ang1 protein elicited partial improvement. CONCLUSION: Cavernous neovascularization using recombinant Ang1 protein is a novel therapeutic strategy for the treatment of ED resulting from type II diabetes. PMID- 20584114 TI - Nicardipine vs. saline injection as treatment for Peyronie's disease: a prospective, randomized, single-blind trial. AB - INTRODUCTION: Various conservative treatments for Peyronie's disease (PD) have been attempted over the years. Intralesional verapamil injection has been tested in prospective randomized studies, but the effect of this treatment seems insufficient. Nicardipine is a calcium antagonist alternative to verapamil and is reportedly more effective in vitro. AIM: The objective of our study was to evaluate the usefulness of intralesional nicardipine injection as a conservative treatment for PD in the transition period of acute and chronic phase. METHODS: Eighty-six patients (age: 38-72 years, mean: 52) were enrolled in this study. A total of 74 patients were assigned randomly to nicardipine group (10 mg diluted in 10 mL of distilled water daily, N=37) and control group (10 mL of saline water, N=37). A total of six injections were administrated biweekly. MEAN OUTCOME MEASURE: The subjects were assessed by International Index of Erectile Function (IIEF)-5 and international pain scale. The plaque size was measured by ultrasonography after 20 ug intracavernosal injection of alprostadil (prostaglandin E1). The penile curvature was also measured by taking a photograph at maximum rigidity. RESULTS: A reduction of pain score was seen throughout the course of treatment in both groups with a significant difference between the nicardipine and control groups (multiple analysis of variance test, P=0.019). A significant improvement of IIEF-5 score occurred only in the nicardipine group at 48 weeks after the initiation of treatment (P<0.01). The plaque size was significantly reduced at 48 weeks only in the nicardipine group (12 points, P=0.0004 by paired t-test). The penile curvature was significantly improved in both groups (P<0.01) without significant difference between them (P=0.14). There were no severe side effects, such as hypotension or other cardiovascular events. CONCLUSION: Our findings indicate that intralesional nicardipine injection is clinically effective as a conservative treatment for PD in the transition period of acute and chronic phase. PMID- 20584116 TI - A protein tyrosine kinase inhibitor, imatinib mesylate (Gleevec), improves erectile and vascular function secondary to a reduction of hyperglycemia in diabetic rats. AB - INTRODUCTION: Erectile dysfunction (ED) afflicts 50% of diabetic men, many of whom experience poor results with phosphodiesterase type 5 inhibitors. The protein tyrosine kinase (PTK) inhibitor imatinib (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland) has therapeutic potential in diabetic men by maintaining beta-cell function. AIM: To determine if imatinib has a beneficial effect on erectile and vascular function in diabetic rats. METHODS: Male Sprague Dawley rats were divided into six groups: (i) control; (ii) imatinib (50mg/kg, daily gavage)-treated control; (iii) diabetic; (iv) preventive imatinib (8 weeks); (v) reversal imatinib (4 weeks untreated diabetes and 4 weeks of treatment); and (vi) insulin (8 weeks)-treated diabetic rats. MAIN OUTCOME MEASURES: After 8 weeks, all groups underwent cavernosal nerve stimulation and measurements of intracavernosal pressure (ICP) and mean arterial pressure (MAP). Contractile and relaxation responses were evaluated using isolated strips of corpus cavernosum smooth muscle (CCSM) and aorta. RESULTS: Diabetic rats exhibited a 32% decrease in weight and fivefold increase in blood glucose levels. Imatinib-treated diabetic rats gained weight and partially improved blood glucose levels. Diabetic rats displayed a decrease in ICP/MAP. While maximum electrical field stimulation- and acetylcholine (ACh)-induced relaxations in CCSM strips from the diabetics were reduced, preventive imatinib or insulin treatment normalized ICP/MAP ratios and improved relaxation responses. ACh responses in diabetic aortas were diminished by 50.1% and restored by imatinib. While contractile responses to phenylephrine in diabetic CCSM were not altered, there was a significant enhancement (59.4 %) in the aortic contractile response in diabetic rats, which was restored by imatinib and insulin treatment. CONCLUSIONS: In diabetic rats, prolonged therapy with imatinib improves diabetes-related ED and vascular function, which may involve normalization of high glucose levels and restoration of PTK activation. Future studies are needed to elaborate on the actions of imatinib on diabetic vascular complications. PMID- 20584115 TI - Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study. AB - INTRODUCTION: Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. AIMS: To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. METHODS: The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 uM) on the tension induced by 0.1 uM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 uM, 0.1 uM, 1 uM) and the production of cAMP and cGMP determined by means of radioimmunoassays. MAIN OUTCOME MEASURES: Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RESULTS: RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119 fold in the presence of CNP or BK, respectively. CONCLUSION: Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways. PMID- 20584117 TI - Morphological and functional evidence for the contribution of the pudendal artery in aging-induced erectile dysfunction. AB - INTRODUCTION: Aging increases the risk of both erectile dysfunction (ED) and cardiovascular disease. These conditions have similar etiologies and commonly coexist. One unifying concept is the role of arterial insufficiency which is a primary factor in the onset of age-related ED. AIM: Based on the novel finding that the pudendal arteries contribute 70% of the total penile vascular resistance, our objective was to morphometrically and functionally characterize this vessel in young and old normotensive rats. METHODS: Erectile function was monitored in 15- and 77-week Sprague-Dawley rats using the apomorphine bioassay (80mg/kg, s.c.). Anesthetized animals were perfusion-fixed, aortic, renal, and internal pudendal arteries were excised, embedded, sectioned, stained, and morphometrically assessed using light microscopy. Hearts were excised, separated, and weighed prior to perfusion. Contractile and relaxation responses to acetylcholine (ACh) and phenylephrine (PE) were assessed by wire myograph. MAIN OUTCOME MEASURES: Erectile function, morphological measurements, concentration response curves to ACh and PE. RESULTS: With age, there were marked decreases in erectile responses compared to younger rats (2.8+/-0.87 vs. 0.3+/-0.58). The pudendal arteries had a relatively small lumen (303+/-13.8um) and a thick medial layer (47+/-2.2um). In aged pudendal arteries, the lumen diameter did not change, and yet the medial layer, cross sectional area, and extracellular matrix were markedly increased. In contrast, the lumen diameter and wall thickness of the aorta and renal arteries in aged rats increased proportionally. An increase in small, round, smooth muscle cells was seen in aged pudendal arteries. Functionally, there were no differences in contractile responses to PE; however, ACh-induced relaxation decreased with age. CONCLUSIONS: In aged rats, erectile function was severely diminished when pudendal arteries had undergone marked phenotypic changes. Specifically, there was endothelial dysfunction and pathological remodeling of this vessel with age, characterized by medial thickening, impaired vasodilation and significantly reduced capacity for penile blood flow. PMID- 20584118 TI - Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis. PMID- 20584119 TI - The EPIFARM study: an observational study in 574 community pharmacies in Spain characterizing patient profiles of men asking for erectile dysfunction medication. AB - INTRODUCTION: Community pharmacists may be an important first point of contact for erectile dysfunction (ED) patients, but to date there are no reports of the characteristics of men approaching pharmacists for ED advice or treatment. AIM: To characterize the profiles of men with and without phosphodiesterase-5 inhibitors (PDE5i) prescription asking for ED treatment at the pharmacy. METHODS: A multicenter, observational, cross-sectional study was conducted in Spanish community pharmacies September-November 2008. Of men asking for ED advice or treatment, each investigator recruited one with and one without PDE5i prescription. Study pharmacists completed a questionnaire of patient demographic, clinical, and behavioural data including the Sexual Health Inventory for Men. MAIN OUTCOME MEASURES: Demographic characteristics and responses to questionnaires. RESULTS: Five hundred and seventy-four pharmacists recruited 1,147 patients; 1,113 were included for analysis. There were no statistical differences between the groups regarding weight, hypertension, diabetes mellitus, hypercholesterolemia, dyslipidemia, depression, or stress. There were no statistical differences in severity of ED (P=0.7892) or proportion of men without ED in each group (P=0.5755). ED symptoms had been present for a mean of 26 months in both groups before first consultation with a healthcare professional. The visit to the pharmacy was the first discussion about ED for 60.2% of the nonprescription group, and 50% of those who had previously discussed ED had done so with a pharmacist in the first instance. In the nonprescription group, 85.1% of men asked for a PDE5i. CONCLUSIONS: Many men approached a community pharmacist for ED treatment and those with and without a PDE5i prescription had an equivalent ED severity and comorbidity profile. Community pharmacists should be trained in current concepts underlying the diagnosis and management of ED to enable them to educate men and encourage them to seek further medical care, increasing the chance of early detection of undiagnosed comorbidities such as cardiovascular disease. PMID- 20584120 TI - Greater tactile sensitivity and less use of immature psychological defense mechanisms predict women's penile-vaginal intercourse orgasm. AB - INTRODUCTION: Previous research has suggested that diminished tactile sensitivity might be associated with reduced sexual activity and function. Research has also demonstrated significant physiological and psychological differences between sexual behaviors, including immature psychological defense mechanisms (associated with various psychopathologies) impairing specifically women's orgasm from penile vaginal intercourse (PVI). AIMS: To examine the extent to which orgasm triggered by PVI (distinguished from other sexual activities) is associated with both greater tactile sensitivity and lesser use of immature psychological defenses. METHODS: Seventy French-Canadian female university students (aged 18-30) had their finger sensitivity measured with von Frey type microfilaments, completed the Defense Style Questionnaire and a short form of the Marlowe-Crowne social desirability scale, and provided details of the 1 month (and ever) frequencies of engaging in, and having an orgasm from, PVI, masturbation, anal intercourse, partner masturbation, and cunnilingus. MAIN OUTCOME MEASURES: Logistic and linear regression prediction of orgasm triggered by PVI from tactile sensitivity, age, social desirability responding, and immature psychological defenses. RESULTS: Having a PVI orgasm in the past month was associated with greater tactile sensitivity (odds ratio=4.0 for each filament point) and less use of immature defense mechanisms (odds ratio=5.1 for each scale point). Lifetime PVI orgasm was associated only with less use of immature defense mechanisms (and lower social desirability responding score). Orgasms triggered by other activities were not associated with either tactile sensitivity or immature defense mechanisms. Tactile sensitivity was also associated with greater past month PVI frequency (inclusion of PVI frequency in a logistic regression model displaced tactile sensitivity), and lesser use of immature defenses was associated with greater past month PVI and PVI orgasm frequencies. CONCLUSIONS: Both diminished physical sensitivity and the presence of specific psychological impairments might decrease the likelihood of women's orgasm from specifically PVI, but not other sexual activities. PMID- 20584121 TI - Sexual arousal in East Asian and Euro-Canadian women: a psychophysiological study. AB - INTRODUCTION: Studies of ethnic differences in self-report measures of sexuality have shown East Asian women to be more sexually conservative and less sexually experienced than Caucasian women. There is also strong evidence supporting the notion of ethnic group differences in general measures of nonsexual psychophysiological arousal; however, there have been no previous studies exploring ethnicity and physiological sexual arousal. AIM: The objective of this study was to explore group differences in self-reported and physiological sexual arousal in Euro-Canadian and East Asian women living in Canada; we also aimed to explore the association between level of acculturation (both mainstream and heritage) and sexual arousal in East Asian women only. METHODS: Seventy-five women (N=38 Euro-Canadian, N=37 East Asian) completed a battery of questionnaires and underwent psychophysiological sexual arousal testing using the vaginal photoplethysmograph. They also completed a self-report measure of subjective arousal before and after erotic stimulus exposure. MAIN OUTCOME MEASURES: All women completed the Female Sexual Function Index, Vancouver Index of Acculturation, and Sexual Beliefs and Information Questionnaire. Change in genital sexual arousal (vaginal pulse amplitude; VPA), and change in subjective sexual arousal were measured during exposure to erotic stimuli. RESULTS: The groups did not differ in the percent increase in VPA induced by erotic stimuli, nor was there a correlation between VPA and subjective sexual arousal. Among East Asian women alone, neither heritage nor mainstream acculturation was correlated with change in VPA. CONCLUSIONS: East Asian and Euro-Canadian women who show similar ratings of sexual behaviors and self-reported sexual arousal do not differ in physiological or subjective arousal induced by erotic stimuli in the laboratory. PMID- 20584122 TI - The relationship between androgens, regulators of collagen metabolism, and Peyronie's disease: a case control study. AB - INTRODUCTION: Changes in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie's Disease (PD). Androgens such as dehydroepiandrosterone sulfate (DHEA-S) and testosterone influence collagen metabolism by modulating the activity of matrix metalloproteases (MMP) and tissue inhibitors of metalloproteases (TIMP). AIM: The aim of this study was to evaluate the interrelationship between androgens (DHEA-S and testosterone), key regulators of collagen metabolism such as insulin-like growth factor (IGF) 1 and IGF Binding Protein 3 (IGF-BP3), the MMP/TIMP system, and PD. METHODS: Age matched PD patients (14) and healthy men (10) who acted as controls were recruited. Blood samples were collected from all subjects in the early morning hours after an overnight fast. MAIN OUTCOME MEASURES: Serum levels of testosterone, sex hormone binding globulin, DHEA-S, 3-alpha-androstanediol glucuronide, pro-MMP-1, MMP-1, MMP-2, TIMP-1, TIMP-2, IGF-1 and IGF-BP3 were measured in both groups. Statistical methods included univariate, bivariate, and multivariate regression models. RESULTS: Levels of DHEA-S (114.5 vs. 169.5 ug/dL; p = 0.03), IGF-BP3 (2.96 vs. 3.79 ug/mL; p = 0.01), and TIMP-1 (173.1 vs. 195 ng/mL; p = 0.01) were significantly lower in PD patients. In contrast, the level of TIMP-2 (102 vs. 85 ng/mL; p = 0.001) was significantly lower in the control group. Using stepwise regression analysis, only TIMP-2 (p < 0.001) and DHEA-S (p = 0.04) were significantly related to PD in the final model (R(2) = 0.63). TIMP-1 and DHEA-S (r = 0.55, p < 0.05) were positively correlated in the PD group, whereas IGF-1 and testosterone (r = -0.54, p < 0.05), and IGF-BP3 and testosterone (r = -0.68, p < 0.05) were negatively correlated in PD patients. CONCLUSIONS: Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observation remain to be established. PMID- 20584123 TI - Vascularized cadaveric fibula flap for treatment of erectile dysfunction following failure of penile implants. AB - INTRODUCTION: Postpriapism erectile dysfunction in patients with sickle cell disease is a particularly devastating condition. Where penile implants have failed, there is no good surgical alternative at present. Free tissue transfer is fraught with risks in patients with sickle cell disease and are not the best option for treatment. AIM: To describe a new surgical technique involving prefabrication of a bone flap for treatment of erectile dysfunction in a patient with sickle cell disease. METHODS: The descending branch of the lateral circumflex femoral artery was isolated and implanted within a cadaveric bone segment. The prefabricated flap was then transferred 2 months later as a neophallus for penile autoaugmentation. RESULTS: Bone scan showed viability of the bone flap after transfer. The patient was able to have vaginal intercourse and successfully achieve orgasm 2 months after the second stage surgery. CONCLUSIONS: Prefabrication of a cadaveric bone flap and subsequent transfer is a novel and effective technique for treatment of erectile dysfunction refractory to medical management. This technique may be particularly useful for "implant cripples," who have no other surgical option. PMID- 20584124 TI - Improved ejaculatory latency, control and sexual satisfaction when PSD502 is applied topically in men with premature ejaculation: results of a phase III, double-blind, placebo-controlled study. AB - INTRODUCTION: PSD502 is a novel aerosolized, lidocaine-prilocaine, spray being developed for the treatment of lifelong premature ejaculation. The clinical profile of PSD502 is described in one of two double-blind, placebo-controlled, phase III studies. AIM: To determine the effect of PSD502 on the Index of Premature Ejaculation (IPE) and intravaginal ejaculatory latency (IELT) of men with lifelong PE. METHODS: Men with lifelong PE who documented an IELT <= 1 minute with two or more of the first three sexual encounters during a 4-week baseline period were randomized to receive double-blind treatment with PSD502 or placebo for 3 months. Patients completed IPE and Premature Ejaculation Profile questionnaires at entry and monthly visits, and recorded stop-watch timed IELT during each encounter. Safety was assessed by collecting adverse event data and standard safety measures. MAIN OUTCOME MEASURES: Stopwatch timed IELT recordings and a patient-reported outcome questionnaire the IPE were used in this study to determine the effect of PSD502 applied topically 5 minutes before intercourse. RESULTS: Two hundred fifty-six men with PE were randomized from 38 centers in the U.S., Canada, and Poland. The geometric mean IELT over the 3-month treatment period increased from a baseline of 0.56 minute and 0.53 minute in the PSD502 and placebo group respectively to 2.60 and 0.80 minute. There were significantly greater increases in the scores for the IPE domains of ejaculatory control, sexual satisfaction and distress in the PSD502 group than in the placebo group, with a mean 5.0 point difference between treatments in change from baseline in the IPE domain for ejaculatory control, 4.6 point difference in change from baseline in the IPE domain for sexual satisfaction, and a 2.5 point difference in change from baseline in the IPE domain for distress. This was supported by improvements in all secondary endpoints. CONCLUSION: In this study, PSD502 applied topically to the glans penis 5 minutes before intercourse showed significantly improved ejaculatory latency, ejaculatory control, sexual satisfaction and distress and was shown to be well tolerated by patients and partners. PMID- 20584125 TI - Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. AB - INTRODUCTION: The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks. AIM: The aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals. METHODS: Forty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months. MAIN OUTCOME MEASURES: Body composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded. RESULTS: There was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period. CONCLUSIONS: There was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy. PMID- 20584126 TI - Pelvimetric dimensions do not impact upon nerve sparing or erectile function recovery in patients undergoing radical retropubic prostatectomy. AB - INTRODUCTION: The impact of unfavorable pelvic anatomy on the likelihood of having a nerve sparing radical retropubic prostatectomy (RRP) and the potential correlation between pelvic dimensions and recovery of erectile function (EF) after RRP have not been previously evaluated. AIM: To determine the impact of different pelvic bony and soft tissue dimensions as well as apical prostate depth on the likelihood of performing bilateral nerve sparing and on recovery of EF after RP. METHODS: Between November 2001 and June 2007, 644 potent men undergoing RRP had preoperative MRI where pelvimetry was performed with bilateral nerve sparing in 504 men. Outcomes including varying degrees of recovery of EF (level 1: normal; level 2: partial erections routinely sufficient for intercourse; level 3: partial erections occasionally sufficient for intercourse) were assessed. Median follow-up was 44.1 (interquartile range: 29.2, 65.3) months. We evaluated independent predictors of performing a bilateral nerve sparing procedure and of recovery of EF using multivariable Cox proportional hazards methods. MAIN OUTCOME MEASURES: Likelihood of performing bilateral nerve sparing as well as recovery of EF after RRP. RESULTS: Patients with higher clinical stage and biopsy Gleason score are less likely to undergo bilateral nerve sparing. Surgeon is also a factor in the likelihood of having bilateral nerve sparing RRP. On multivariate Cox regression analysis, factors predictive of recovery of EF were age, pretreatment erectile function, surgeon, and modified Charlson score. None of the pelvimetric dimensions were significant predictors of any degree of recovery of EF. However, the study is limited by its retrospective nature and by being based on MRI evaluations useful for cancer staging rather than anatomical evaluation of pelvimetric dimensions. CONCLUSIONS: We did not find unfavorable pelvic anatomy to impact the likelihood of performing a nerve sparing procedure or to be predictive of any degree of recovery of EF after RRP. PMID- 20584127 TI - Radiofrequency treatment of vaginal laxity after vaginal delivery: nonsurgical vaginal tightening. AB - INTRODUCTION: All women who have given birth vaginally experience stretching of their vaginal tissue. Long-term physical and psychological consequences may occur, including loss of sensation and sexual dissatisfaction. One significant issue is the laxity of the vaginal introitus. AIM: To evaluate safety and tolerability of nonsurgical radiofrequency (RF) thermal therapy for treatment of laxity of the vaginal introitus after vaginal delivery. We also explored the utility of self-report questionnaires in assessing subjective effectiveness of this device. METHODS: Pilot study to treat 24 women (25-44 years) once using reverse gradient RF energy (75-90 joules/cm(2) ), delivered through the vaginal mucosa. Post-treatment assessments were at 10 days, 1, 3, and 6 months. MAIN OUTCOME MEASURES: Pelvic examinations and adverse event reports to assess safety. The author modified Female Sexual Function Index (mv-FSFI) and Female Sexual Distress Scale-Revised (FSDS-R), Vaginal Laxity and Sexual Satisfaction Questionnaires (designed for this study) to evaluate both safety and effectiveness, and the Global Response Assessment to assess treatment responses. RESULTS: No adverse events were reported; no topical anesthetics were required. Self-reported vaginal tightness improved in 67% of subjects at one month post treatment; in 87% at 6 months (P<0.001). Mean sexual function scores improved: mv FSFI total score before treatment was 27.6 +/- 3.6, increasing to 32.0 +/- 3.0 at 6 months (P < 0.001); FSDS-R score before treatment was 13.6 +/- 8.7, declining to 4.3 +/- 5.0 at month 6 post-treatment (P < 0.001). Twelve of 24 women who expressed diminished sexual satisfaction following their delivery; all reported sustained improvements on SSQ at 6 months after treatment (P = 0.002). CONCLUSION: The RF treatment was well tolerated and showed an excellent 6-month safety profile in this pilot study. Responses to the questionnaires suggest subjective improvement in self-reported vaginal tightness, sexual function and decreased sexual distress. These findings warrant further study. PMID- 20584128 TI - Portuguese version of Cues for Sexual Desire Scale: the influence of relationship duration. AB - INTRODUCTION: It is well established that sexual desire is a triggered response to effective sexual stimuli. Factors that trigger women's sexual desire can change over time and circumstances. The Cues for Sexual Desire Scale (CSDS) is a valuable assessment tool to measure the range and magnitude of such stimuli. AIM: To investigate the psychometric properties of CSDS within a Portuguese community sample of women; to examine the influence of relationship duration on CSDS scores. METHODS: Portuguese women (N=3,687) over age 18 completed a web-based survey of previously pilot-tested items. Main Outcome Measures. Factor structure and internal consistency of CSDS scores; differences between women in longer-term (more than five years) and shorter-term (less than three years) relationships; predictors of CSDS scores. RESULTS: A factor analysis revealed a difference in factor structure between the Portuguese and the original (English) version of CSDS. A five factor solution explained 58.3% of the total variance. The CSDS demonstrated good reliability (Cronbach's = 0.913). All subscales had alpha values greater than 0.85. Women in longer-term relationships had significantly fewer cues for sexual desire (M = 124) compared to women in shorter-term relationships (M = 128), t(1,879) = 3.7, P < 0.001. Older women (beta = -0.075; P < 0.001), and longer term relationships (beta = -0.056; P < 0.05), were significant predictors of lower CSDS-P scores. Additionally, women who masturbated (beta = 0.172; P < 0.001) and reached orgasm easily (beta = 0.059; P < 0.001) had higher scores for CSDS-P. CONCLUSIONS: The CSDS is a useful instrument for identifying triggers that facilitate sexual desire in Portuguese women. Women in longer-term relationships reported fewer cues compared to women in shorter-term relationships. This has clinical implications and suggests that encouraging women to consider newer and varied cues that might evoke or enhance sexual desire may be one means of addressing concerns with low sexual desire. PMID- 20584129 TI - Durability of response following cessation of tadalafil taken once daily as treatment for erectile dysfunction. AB - INTRODUCTION: Research has focused on improvement of erectile function during treatment with phosphodiesterase type 5 (PDE5) inhibitors, but less is known about what occurs after treatment cessation. AIM: The aim of this retrospective analysis was to examine durability of response, defined as sustainability of erectogenic benefits following treatment cessation, in men with erectile dysfunction (ED) following long-term treatment with daily tadalafil. METHODS: The subjects (N=160) had participated in a 12-week double-blind trial followed by a one-year, open-label extension of tadalafil 5mg once daily. The extension was followed by a 4-week, treatment-free follow-up period. A total of 158 subjects completed International Index of Erectile Function-Erectile Function (IIEF-EF) domain score and were included in this analysis. MAIN OUTCOME MEASURES: The primary measures for this analysis were changes in ED severity category as captured by the IIEF-EF domain score. RESULTS: At the end of the 1-year open label treatment period, a majority (86.1%, n=136) of subjects had either improved by at least one ED severity category (e.g., Severe to Moderate) (n=128), or maintained Normal erectile function (EF domain score >=26) (n=8), compared to baseline. Following the 4-week, treatment-free period, 63 of those subjects (46.3% of the 136 subjects) had continued improvement of at least one ED severity category (n=61) or maintained scores in the Normal category (n=2) compared with baseline. Subjects who showed a sustained benefit of treatment were considered to have demonstrated a "durable response." Seventy-three subjects (53.7%) did not have a durable response following treatment cessation. A few patient characteristics were associated with durability of response. CONCLUSIONS: Of those men who demonstrated improved erectile function while taking tadalafil 5mg once daily for 1 year, 46.3% continued to show improvement compared with baseline following a 4-week treatment free period. Durability of response should be a focus of future research. PMID- 20584130 TI - Prevalence, risk factors, and predictors of female sexual dysfunction in a primary care setting: a survey finding. AB - INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent sexual health problem but poorly investigated at the primary care level. AIM: This article examines the prevalence of sexual dysfunction and its possible risk factors associated with women at high risk of FSD in a hospital-based primary practice. METHODS: A validated Malay version of the Female Sexual Function Index (MVFSFI) was utilized to determine FSD in a cross-sectional study design, involving 163 married women, aged 18-65 years, in a tertiary hospital-based primary care clinic in Kuala Lumpur, Malaysia. Sociodemographic, marital profile, health, and lifestyle for women at high risk of FSD and those who were not at high risk were compared and their risk factors were determined. MAIN OUTCOME MEASURES: Prevalence of FSD in Malaysian women based on the MVFSFI, and its risk factors for developing FSD. RESULTS: Some 42 (25.8%) out of 163 women had sexual dysfunction. Prevalence of sexual dysfunction increased significantly with age. Sexual dysfunctions were detected as desire problem (39.3%), arousal problem (25.8%), lubrication problem (21.5%), orgasm problem (16.6%), satisfaction problem (21.5%) and pain problems (16.6%). Women at high risk of FSD were significantly associated with age (OR 4.1, 95% CI 1.9 to 9.0), husband's age (OR 4.3 95% C.I 1.9 to 9.3), duration of marriage (OR 3.3, 95% CI 1.6 to 6.8), medical problems (OR 8.5, 95% CI 3.3 to 21.7), menopausal status (OR 6.6, 95% CI 3.1 to 14.3), and frequency of sexual intercourse (OR 10.7, 95% CI 3.6 to 31.7). Multivariate analysis showed that medical problem (adjusted OR 4.6, 95% CI 1.6 to 14.0) and frequency of sexual intercourse (adjusted OR 7.2, 95% CI 2.1 to 24.0) were associated with increased risk of having FSD. Those who practiced contraception were less likely to have FSD. CONCLUSION: Sexual health problems are prevalent in women attending primary care clinic where one in four women were at high risk of FSD. Thus, primary care physician should be trained and prepared to address this issue. PMID- 20584131 TI - Colonization history and genetic diversity: adaptive potential in early stage invasions. AB - The introduction of Anolis cristatellus from the multiple species anole community of Puerto Rico in the Greater Antilles to the island of Dominica in the Lesser Antilles, with its solitary endemic anole, provides an example of a very recent, timed, single colonization. We investigate the geographic origin and adaptive potential of the Dominican population using a range of methods including mtDNA phylogeography, nuclear microsatellite variation and multiple paternity studies, as well as heritability estimates, common garden experiments and comparative geographic studies of quantitative scalation traits. Phylogeographic analysis of NADH2 and microsatellite studies suggests that the Dominican population arose from a set of individuals from the central west area of Puerto Rico within their endemic range. The multiple-individual inoculation, together with sperm storage and evidence of multiple paternity indicate genetic variability and suggest the potential for adaptation by natural selection. Estimates of heritability, common garden experiments and broad sense Q(ST)/F(ST) ratios, linked to replicated comparisons along elevational transects go some way to suggesting that the invasive populations may be adapting by natural selection, in parallel with the endemic anole, in the brief period since their introduction. PMID- 20584132 TI - Molecular evolution of shattering loci in U.S. weedy rice. AB - Cultivated rice fields worldwide are plagued with weedy rice, a conspecific weed of cultivated rice (Oryza sativa L.). The persistence of weedy rice has been attributed, in part, to its ability to shatter (disperse) seed prior to crop harvesting. In the United States, separately evolved weedy rice groups have been shown to share genomic identity with exotic domesticated cultivars. Here, we investigate the shattering phenotype in a collection of U.S. weedy rice accessions, as well as wild and cultivated relatives. We find that all U.S. weedy rice groups shatter seeds easily, despite multiple origins, and in contrast to a decrease in shattering ability seen in cultivated groups. We assessed allelic identity and diversity at the major shattering locus, sh4, in weedy rice; we find that all cultivated and weedy rice, regardless of population, share similar haplotypes at sh4, and all contain a single derived mutation associated with decreased seed shattering. Our data constitute the strongest evidence to date of an evolution of weeds from domesticated backgrounds. The combination of a shared cultivar sh4 allele and a highly shattering phenotype, suggests that U.S. weedy rice have re-acquired the shattering trait after divergence from their progenitors through alternative genetic mechanisms. PMID- 20584133 TI - Seeing red: the origin of grain pigmentation in US weedy rice. AB - Weedy forms of crop species infest agricultural fields worldwide and are a leading cause of crop losses, yet little is known about how these weeds evolve. Red rice (Oryza sativa), a major weed of cultivated rice fields in the US, is recognized by the dark-pigmented grain that gives it its common name. Studies using neutral molecular markers have indicated a close relationship between US red rice and domesticated rice, suggesting that the weed may have originated through reversion of domesticated rice to a feral form. We have tested this reversion hypothesis by examining molecular variation at Rc, the regulatory gene responsible for grain pigmentation differences between domesticated and wild rice. Loss-of-function mutations at Rc account for the absence of proanthocyanidin pigments in cultivated rice grains, and the major rc domestication allele has been shown to be capable of spontaneous reversion to a functional form through additional mutations at the Rc locus. Using a diverse sample of 156 weedy, domesticated and wild Oryzas, we analysed DNA sequence variation at Rc and its surrounding 4 Mb genomic region. We find that reversion of domestication alleles does not account for the pigmented grains of weed accessions; moreover, we find that haplotypes characterizing the weed are either absent or very rare in cultivated rice. Sequences from genomic regions flanking Rc are consistent with a genomic footprint of the rc selective sweep in cultivated rice, and they are compatible with a close relationship of red rice to Asian Oryzas that have never been cultivated in the US. PMID- 20584134 TI - Strong genetic differentiation and postglacial origin of populations in the marine midge Clunio marinus (Chironomidae, Diptera). AB - The marine midge Clunio marinus (Chironomidae, Diptera) is characterized by a one dimensional distribution along the European Atlantic coast, where its lunar and circadian emergence rhythms are genetically adapted to the local tidal regimes, resulting in a series of 'temporal races'. Clunio marinus is restricted to rocky coasts and thus the temporal races occur in different rocky patches. We studied 10 populations of Clunio marinus from five different regions, spanning the major rocky mainland coasts from Spain to Norway, using amplified fragment length polymorphisms (AFLP), microsatellites and mitochondrial cytochrome oxidase I (COI) sequences. Star-like patterns of COI haplotypes within regions indicate postglacial colonization. A high degree of shared polymorphisms in AFLP markers suggests colonization from a single source, implying postglacial evolution of timing adaptations in relation to the local tidal regime. In contrast, no COI haplotypes are shared among regions. We hypothesize that different levels of differentiation of nuclear vs. mitochondrial markers in the source region were carried forward during postglacial expansion. Despite the recent origin of populations, all markers reveal distinct genetic differentiation between rocky coasts on a scale of 650-1150 km. Differentiation between rocky coasts is not correlated to timing adaptations, suggesting that geographic isolation is prevalent between rocky coasts and that this facilitated the evolution of local timing adaptations. At the same time there is little genetic differentiation within rocky coasts on a scale of 2-6 km; leaving open the possibility that within rocky coasts with large variation in tidal regimes, temporal adaptations evolved in the face of gene flow. PMID- 20584135 TI - Evolution of host breadth in broad interactions: mycorrhizal specificity in East Asian and North American rattlesnake plantains (Goodyera spp.) and their fungal hosts. AB - Host breadth is often assumed to have no evolutionary significance in broad interactions because of the lack of cophylogenetic patterns between interacting species. Nonetheless, the breadth and suite of hosts utilized by one species may have adaptive value, particularly if it underlies a common ecological niche among hosts. Here, we present a preliminary assessment of the evolution of mycorrhizal specificity in 12 closely related orchid species (genera Goodyera and Hetaeria) using DNA-based methods. We mapped specificity onto a plant phylogeny that we estimated to infer the evolutionary history of the mycorrhiza from the plant perspective, and hypothesized that phylogeny would explain a significant portion of the variance in specificity of plants on their host fungi. Sampled plants overwhelmingly associated with genus Ceratobasidium, but also occasionally with some ascomycetes. Ancestral mycorrhizal specificity was narrow in the orchids, and broadened rarely as Goodyera speciated. Statistical tests of phylogenetic inertia suggested some support for specificity varying with increasing phylogenetic distance, though only when the phylogenetic distance between suites of fungi interacting with each plant taxon were taken into account. These patterns suggest a role for phylogenetic conservatism in maintaining suits of fungal hosts among plants. We stress the evolutionary importance of host breadth in these organisms, and suggest that even generalists are likely to be constrained evolutionarily to maintaining associations with their symbionts. PMID- 20584136 TI - Phylogeography of the marine macroalga Sargassum hemiphyllum (Phaeophyceae, Heterokontophyta) in northwestern Pacific. AB - Sargassum hemiphyllum is commonly found in Japan and Korea, with a variety, var. chinense, that is found distributed in the southern Chinese coast. We previously reported distinct genetic differentiation between the two taxa based on the PCR RFLP data of plastid RubiscoL-S spacer. The present study aims at elucidating the phylogeographic pattern of S. hemiphyllum based on more markers in the nuclear and extranuclear genomes, with a view to reveal the occurrence of hybridization. The two allopatrically distributed taxa were found to be genetically distinct in nuclear ITS2, plastidial Rubisco (Rbc) and mitochondrial TrnW_I (Trn) spacers. Their divergence was postulated to be attributable to the vicariant event which resulted from the isolation of the Sea of Japan during the late Miocene (6.58 11.25 Mya). Divergence within both S. hemiphyllum and the chinense variety was observed based on Trn spacer, while the divergence in S. hemiphyllum was further confirmed in Rbc spacer. This divergence appears to correspond to the separation of the Japanese populations between the Sea of Japan and the Pacific that occurred around 0.92-2.88 Mya (the early Pleistocene). The presence of an ITS2 clone resembling var. chinense sequences in a Japanese population of S. hemiphyllum (JpNS) raises the possibility of the introgression of var. chinense individuals into S. hemiphyllum population. Compared to that between S. hemiphyllum and the chinense variety, hybridization among the Japanese and Korean populations of S. hemiphyllum is highly probable as all these individuals share a pool of nuclear ITS2 sequences, possibly attributable to incomplete concerted evolution of ITS2. PMID- 20584137 TI - Detection and management of an outbreak of equine herpesvirus type 1 infection and associated neurological disease in a veterinary teaching hospital. AB - BACKGROUND: Because of the serious disease sequelae associated with equine herpesvirus type 1 (EHV-1) infections, awareness and control measures used to control outbreaks are important issues for all horse populations. OBJECTIVES: Describe the occurrence and management of an outbreak of EHV-1 infection at a veterinary hospital. ANIMALS: Horses hospitalized at a referral veterinary hospital. METHODS: A horse with myeloencephalopathy associated with EHV-1 infection (EHM) was admitted for diagnostic evaluation and treatment under strict infection control procedures. We describe the occurrence and management of a nosocomial outbreak of EHV-1 infections associated with admission of this patient. RESULTS: Despite institution of rigorous biosecurity precautions at the time of admission of the index case, EHV-1 infections spread to 6 other horses that were hospitalized at the James L. Voss Veterinary Teaching Hopsital, including 2 that served as sources of infection for horses on their home premises after discharge. Infection with EHV-1 was confirmed by polymerase chain reaction (PCR) and by seroconversion documented by glycoprotein G ELISA. A voluntary quarantine was imposed and admissions were restricted to prevent additional horses from being exposed. Quarantine duration was abbreviated by serial testing of all horses with PCR. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings illustrate the contagious disease risk that can accompany management of horses with EHM. Horses with active nasal EHV-1 shedding should be isolated in an airspace that is separate from other horses by strictly enforced biosecurity and isolation procedures. Serial testing with PCR may be a useful adjunct to determine when the risk of transmission has been minimized. PMID- 20584138 TI - Intravenous administration of azumolene to reverse malignant hyperthermia in swine. AB - BACKGROUND: The efficacy of intravenous (IV) administration of azumolene (Az), an analogue 30-fold more soluble than dantrolene, on pigs susceptible to malignant hyperthermia (MH) is incompletely understood. OBJECTIVE: To evaluate efficacy of Az on MH crisis in pigs. ANIMALS: Eight normal (MHN) and 7 susceptible to MH (MHS) pigs (Landrace * Large White * Pietran). METHODS: Prospective, laboratory trial. Hypermetabolic crisis was observed in MHS pigs, but not in MHN pigs, after a combined administration of inhaled halothane (1.5%) and IV injection of succinylcholine (SCh; 2.5 mg/kg). Susceptibility was confirmed using a caffeine and halothane contracture test. Az was administered 15 minutes after administration of SCh. RESULTS: Respiratory acidosis (pH 7.16 +/- 0.02; Pco(2) , 46.2 +/- 9.1 mmHg, HCO(3) , 22.5 +/- 2.3 mmol/L), fever (38.2 +/- 1.1 degrees C), cardiac arrhythmias, and muscle contracture were observed in MHS pigs. MHS pigs (n = 5) treated with Az (2 mg/kg IV) survived the crisis with attenuation of signs (pH 7.30 +/- 0.10; Pco(2) , 36.3 +/- 4.5 mmHg; HCO(3) , 22.9 +/- 2.3 mmol/L) and recovery of normal muscle tone and cardiac rhythm. CONCLUSIONS AND CLINICAL IMPORTANCE: Az represents a possible substitute for dantrolene to reverse MH crisis in susceptible pigs. PMID- 20584139 TI - Molecular investigation of the viral kinetics of equine herpesvirus-1 in blood and nasal secretions of horses after corticosteroid-induced recrudescence of latent infection. AB - BACKGROUND: Recrudescence of latent equine herpesvirus 1 (EHV-1) with subsequent viral shedding via nasal secretions is a potential source of infection for susceptible horses and has been implicated in outbreaks occurring in closed populations. OBJECTIVES: To describe the viral kinetics of reactivated EHV-1 in blood and nasal secretions from latently infected horses after administration of corticosteroids, and to study the infectious nature of reactivated EHV-1 to sentinel horses. ANIMALS: Eight healthy horses. METHODS: Four horses infected 4 months previously with EHV-1 received dexamethasone on 5 consecutive days. Four seronegative horses served as sentinels and had direct contact with the latently infected horses. All horses were monitored daily for development of clinical signs. Whole blood and nasal secretions were collected daily for molecular detection and cell culture of EHV-1. Serum was collected weekly for the detection of antibodies against EHV-1. RESULTS: All horses in the latently infected group showed transient molecular detection of EHV-1 in blood and nasal secretions, but only 1 horse developed fever. Three latently infected horses developed an increase in antibody concentrations against EHV-l. Viral cultures remained negative for all latently infected horses after corticosteroid administration. None of the sentinel horses developed clinical signs, viremia, viral shedding, or seroconversion. CONCLUSIONS AND CLINICAL IMPORTANCE: EHV-1 was successfully reactivated after corticosteroid administration in latently infected horses. However, transmission of reactivated virus to sentinel horses was unsuccessful. Failure to effectively transmit EHV-1 to susceptible horses may have resulted from the low level and short period of viral shedding in latently infected horses. PMID- 20584140 TI - Ventricular arrhythmias during race recovery in Standardbred Racehorses and associations with autonomic activity. AB - BACKGROUND: A lack of information on normal heart rhythm at maximal effort hampers investigation of poor performance and sudden death in Standardbred racing. HYPOTHESIS/OBJECTIVE: To characterize rhythm variations during scheduled racing in clinically normal Standardbred horses. ANIMALS: Two hundred and eighty eight Standardbred horses competing in 40 scheduled races at a Southern Ontario racetrack. METHODS: Observational study, convenience sampling: Heart rhythm was monitored by ECG from harnessing to postrace recovery and assessed visually and by examining heart rate intervals. Rhythm variations were used as response variables in multivariate analysis of race records detailing signalment, race, and race outcome. RESULTS: Monitoring involved 345 individual horse or race events. Occasional, isolated premature cycles, only, occurred during the race. Postrace, sudden cardiac slowing (punctuated deceleration [PD]) appeared in 42 events (12.2%). Only premature ventricular complexes were exhibited in 40 events postrace (11.6%), whereas 55 (15.9%) exhibited complex ventricular arrhythmias (CVA) including torsades-like polymorphic ventricular tachycardia, 34.5% of these being closely associated with PD (odds ratio = 8). Predispositions to CVA were found for horses parked at the 1/2 mile (odds ratio = 3), and trotters breaking in the stretch (odds ratio = 38). Horses spontaneously reverted to sinus rhythm and no sudden death events were encountered. CONCLUSIONS AND CLINICAL IMPORTANCE: Arrhythmias occur frequently in racing Standardbreds during cardiac deceleration, often associated with sudden, rapid increases in vagal tone. Circumstances imposing unusual demand and racing at the trot appear to predispose. Findings provide insight into possible mechanisms of sudden death. PMID- 20584141 TI - A clinical index for disease activity in cats with chronic enteropathy. AB - BACKGROUND: There is a need for a clinically useful, quantitative index for measurement of disease activity in cats with chronic enteropathy (CE). OBJECTIVE: To develop a numerical activity index that is of practical value to clinicians treating CE in cats. ANIMALS: Eighty-two cats with CE. METHODS: Retrospective case review of 59 cats diagnosed with inflammatory bowel disease (IBD). Prospective validation study of 23 cats having either IBD or food-responsive enteropathy (FRE). Multivariate regression analysis was used to identify which combination of clinical and laboratory variables were best associated with intestinal inflammation of IBD. This combination of variables was expressed in a score that was used as an activity index for the prospective assessment of disease activity and of the effect of treatment in cats with IBD or FRE. RESULTS: The combination of gastrointestinal signs, endoscopic abnormalities, serum total protein, serum alanine transaminase/alkaline phosphatase activity, and serum phosphorous concentration had the best correlation with histopathologic inflammation and comprise the feline chronic enteropathy activity index (FCEAI). Positive treatment responses in cats with CE were accompanied by significant (P < .05) reductions in FCEAI scores after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: The FCEAI is a simple numerical measure of inflammatory activity in cats with CE. The scoring index can be reliably used in the initial assessment of disease severity for both IBD and FRE and as a measure of clinical response to treatment for these disorders. PMID- 20584142 TI - Diagnostic accuracy of d-dimer and other peritoneal fluid analysis measurements in dairy cows with peritonitis. AB - BACKGROUND: Peritoneal fluid analysis in cattle traditionally includes the classic parameters despite the fact that they have only moderate diagnostic accuracy and often fail to identify the pathogenesis or etiological factors. Therefore additional parameters recently have been established to improve diagnostic precision. In a recent study, reference ranges for several of these parameters have been proposed in dairy cows. HYPOTHESIS/OBJECTIVES: The aim of this observational study was to assess the diagnostic value of D-Dimer and other measurements of peritoneal fluid analysis in dairy cows with peritonitis. ANIMALS: The study included 110 Holstein-Friesian cows grouped into cows with peritonitis (n = 47) and cows without peritonitis (n = 63). METHODS: Peritoneal fluid was obtained by abdominocentesis. Total protein, albumin, glucose, cholesterol, fibrinogen, l-lactate, D-Dimer, lactate dehydrogenase (LDH), alkaline phosphatase, creatine phosphokinase, white blood cell, and red blood cell were determined in peritoneal fluid and venous blood. Serum-ascites albumin gradient (SAAG) and ratios of peritoneal fluid-venous blood were calculated. Sensitivity (SN) and specificity (SP) were calculated and receiver operating characteristic curve analysis performed. RESULTS: Peritoneal fluid D-Dimer was most accurate in diagnosing peritonitis in cows (SN and SP>95.0%). Total protein concentration, LDH and LDH ratio, and SAAG had sensitivities between 49.0 and 67.1%, and specificities between 88.4 and 95.5%. A low-peritoneal fluid glucose concentration was found to be highly indicative of septic peritonitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of the recently introduced parameters may increase the diagnostic value of peritoneal fluid analysis and provide additional specific information. Therefore these measurements should be included in the routine procedure. PMID- 20584143 TI - Outbreak of salmonellosis caused by Salmonella enterica serovar Newport MDR-AmpC in a large animal veterinary teaching hospital. AB - BACKGROUND: Nosocomial salmonellosis is an important problem for large animal veterinary teaching hospitals (VTHs). OBJECTIVE: To describe failure of an Infection Control Program (ICP) that resulted in an outbreak of salmonellosis caused by Salmonella Newport multidrug resistant (MDR)-AmpC at a large animal VTH. ANIMALS: Sixty-one animals identified with the outbreak strain of Salmonella. METHODS: Retrospective study: Data collected included signalment, presenting complaint, duration of hospitalization, discharge status, and financial information. Phenotypic and genotypic characterization was performed on Salmonella isolates. RESULTS: The outbreak occurred despite an existing ICP; the ICP was reviewed and weaknesses identified. Routine patient surveillance was not performed before or during the outbreak; fecal sampling was triggered only by a patient algorithm based on clinical signs. Sixty-one animals were infected with the outbreak strain of S. Newport, and the majority were horses (n = 54). Case fatality rate was 36.1%. S. Newport isolates demonstrated high genetic similarity (Dice >= 0.96), and all had the MDR-AmpC phenotype. Environmental persistence of the organism necessitated complete hospital closure, extensive decontamination, and remediation of the facility. A paradigm shift in the relevance of biosecurity in a VTH and the establishment of a stringent ICP were integral components of successful hospital reopening. CONCLUSIONS AND CLINICAL IMPORTANCE: An ineffective ICP resulted in a nosocomial outbreak caused by a MDR S. Newport in a VTH. Closure of a VTH affected all missions of the institution and had substantial financial impact (US$4.12 million). PMID- 20584144 TI - Population dynamics of American horseshoe crabs--historic climatic events and recent anthropogenic pressures. AB - Populations of the American horseshoe crab, Limulus polyphemus, have declined, but neither the causes nor the magnitude are fully understood. In order to evaluate historic demography, variation at 12 microsatellite DNA loci surveyed in 1218 L. polyphemus sampled from 28 localities was analysed with Bayesian coalescent-based methods. The analysis showed strong declines in population sizes throughout the species' distribution except in the geographically isolated southern-most population in Mexico, where a strong increase in population size was inferred. Analyses suggested that demographic changes in the core of the distribution occurred in association with the recolonization after the Ice Age and also by anthropogenic effects, such as the past overharvest of the species for fertilizer or the current use of the animals as bait for American eel (Anguilla rostrata) and whelk (Busycon spp.) fisheries. This study highlights the importance of considering both climatic changes and anthropogenic effects in efforts to understand population dynamics--a topic which is highly relevant in the ongoing assessments of the effects of climate change and overharvest. PMID- 20584145 TI - Phylogeographic structure of Hippophae tibetana (Elaeagnaceae) highlights the highest microrefugia and the rapid uplift of the Qinghai-Tibetan Plateau. AB - The uplift of the Qinghai-Tibetan Plateau (QTP) dramatically changed the topography and climate of Asia and affected the biodiversity of the plateau and its adjacent areas. However, the effects of the uplift on the dispersal, differentiation and adaptation of plants remain a puzzle when the date and processes of the uplift cannot be determined with certainty and the impacts of the Quaternary glaciations on plants on the QTP are unknown. To clarify the relationships among plants on the QTP with the plateau uplift and the Quaternary glaciations, the cpDNA trnT-trnF regions of 891 individuals from 37 populations of Hippophae tibetana, endemic to the QTP, were sequenced in the present study. A total of 50 haplotypes were found and a strong phylogeographic structure was revealed (N(ST) = 0.854, G(ST) = 0.611, N(ST) > G(ST), P < 0.01). The results show that three main lineages of the present populations of H. tibetana occupy the western, the middle, and the eastern geographical range, respectively, and their divergence time dates back to 3.15 Ma before present. Of 50 haplotypes, 33 (66%) are private haplotypes, which are restricted to single populations. These private haplotypes are scattered throughout the present geographical range of H. tibetana and originated from multiple differentiations in many lineages during more than 1.0 Ma period, strongly suggesting that multiple microrefugia of H. tibetana existed throughout the present geographical range during the last glacial maximum (LGM) and even earlier glaciations. Additionally, the average elevation of present populations is over 4500 m in the west and the equilibrium line of glaciers in the LGM was 500-300 m lower than present in the major interior part of the plateau suggesting that at most sites in the west, LGM microrefugia of H. tibetana may have been above 4000 m above sea level, the highest of all known refugia. Moreover, the divergence times among and within the three lineages and their distinct distributions as well as dispersal barriers support the theory of the recent and rapid uplift of the QTP. The rapid uplift of the plateau within the last 3.4 Ma and the associated environmental changes may have affected the dispersal and differentiation of H. tibetana and shaped its phylogeographic structure. PMID- 20584146 TI - Genetic analysis of two phosphodiesterases reveals cyclic diguanylate regulation of virulence factors in Dickeya dadantii. AB - Cyclic diguanylate (c-di-GMP) is a second messenger implicated in the regulation of various cellular properties in several bacterial species. However, its function in phytopathogenic bacteria is not yet understood. In this study we investigated a panel of GGDEF/EAL domain proteins which have the potential to regulate c-di-GMP levels in the phytopathogen Dickeya dadantii 3937. Two proteins, EcpB (contains GGDEF and EAL domains) and EcpC (contains an EAL domain) were shown to regulate multiple cellular behaviours and virulence gene expression. Deletion of ecpB and/or ecpC enhanced biofilm formation but repressed swimming/swarming motility. In addition, the ecpB and ecpC mutants displayed a significant reduction in pectate lyase production, a virulence factor of this bacterium. Gene expression analysis showed that deletion of ecpB and ecpC significantly reduced expression of the type III secretion system (T3SS) and its virulence effector proteins. Expression of the T3SS genes is regulated by HrpL and possibly RpoN, two alternative sigma factors. In vitro biochemical assays showed that EcpC has phosphodiesterase activity to hydrolyse c-di-GMP into linear pGpG. Most of the enterobacterial pathogens encode at least one T3SS, a major virulence factor which functions to subvert host defences. The current study broadens our understanding of the interplay between c-di-GMP, RpoN and T3SS and the potential role of c-di-GMP in T3SS regulation among a wide range of bacterial pathogens. PMID- 20584147 TI - Role of inositol 1,4,5-triphosphate signalling in gravitropic and phototropic gene expression. AB - Plants sense light and gravity to orient their direction of growth. One common component in the early events of both phototropic and gravitropic signal transduction is activation of phospholipase C (PLC), which leads to an increase in inositol 1,4,5-triphosphate (InsP(3)) levels. The InsP(3) signal is terminated by hydrolysis of InsP(3) through inositolpolyphosphate-5-phosphatases (InsP 5 ptases). Arabidopsis plants expressing a heterologous InsP 5-ptase have low basal InsP(3) levels and exhibit reduced gravitropic and phototropic bending. Downstream effects of InsP(3)-mediated signalling are not understood. We used comparative transcript profiling to characterize gene expression changes in gravity- or light-stimulated Arabidopsis root apices that were manipulated in their InsP(3) metabolism either through inhibition of PLC activity or expression of InsP 5-ptase. We identified InsP(3)-dependent and InsP(3)-independent co regulated gene sets in response to gravity or light stimulation. Inhibition of PLC activity in wild-type plants caused similar changes in transcript abundance in response to gravitropic and phototropic stimulation as in the transgenic lines. Therefore, we conclude that changes in gene expression in response to gravitropic and phototropic stimulation are mediated by two signal transduction pathways that vary in their dependence on changes in InsP(3). PMID- 20584148 TI - Oxylipin channelling in Nicotiana attenuata: lipoxygenase 2 supplies substrates for green leaf volatile production. AB - Lipoxygenases (LOXs) are key enzymes in the biosynthesis of oxylipins, and catalyse the formation of fatty acid hydroperoxides (HPs), which represent the first committed step in the synthesis of metabolites that function as signals and defences in plants. HPs are the initial substrates for different branches of the oxylipin pathway, and some plant species may express different LOX isoforms that supply specific branches. Here, we compare isogenic lines of the wild tobacco Nicotiana attenuata with reduced expression of NaLOX2 (irlox2) or NaLOX3 (irlox3) to determine the role of these different LOX isoforms in supplying substrates for two different pathways: green leaf volatiles (GLVs) and jasmonic acid (JA). Reduced NaLOX2 expression strongly decreased the production of GLVs without influencing the formation of JA and JA-related secondary metabolites. Conversely, reduced NaLOX3 expression strongly decreased JA biosynthesis, without influencing GLV production. The temporal expression of NaLOX2 and NaLOX3 also differed after elicitation; NaLOX3 was rapidly induced, attaining highest transcript levels within 1 h after elicitation, whereas NaLOX2 transcripts reached maximum levels after 14 h. These results demonstrate that N. attenuata channels the flux of HPs through the activities of different LOXs, leading to different direct and indirect defence responses mediating the plant's herbivore resistance. PMID- 20584149 TI - Overexpression of yeast spermidine synthase impacts ripening, senescence and decay symptoms in tomato. AB - Polyamines (PAs) are ubiquitous, polycationic biogenic amines that are implicated in many biological processes, including plant growth and development, but their precise roles remain to be determined. Most of the previous studies have involved three biogenic amines: putrescine (Put), spermidine (Spd) and spermine (Spm), and their derivatives. We have expressed a yeast spermidine synthase (ySpdSyn) gene under constitutive (CaMV35S) and fruit-ripening specific (E8) promoters in Solanum lycopersicum (tomato), and determined alterations in tomato vegetative and fruit physiology in transformed lines compared with the control. Constitutive expression of ySpdSyn enhanced intracellular levels of Spd in the leaf, and transiently during fruit development, whereas E8-ySpdSyn expression led to Spd accumulation early and transiently during fruit ripening. The ySpdSyn transgenic fruits had a longer shelf life, reduced shriveling and delayed decay symptom development in comparison with the wild-type (WT) fruits. An increase in shelf life of ySpdSyn transgenic fruits was not facilitated by changes in the rate of water loss or ethylene evolution. Additionally, the expression of several cell wall and membrane degradation-related genes in ySpdSyn transgenic fruits was not correlated with an extension of shelf life, indicating that the Spd-mediated increase in fruit shelf life is independent of the above factors. Crop maturity, indicated by the percentage of ripening fruits on the vine, was delayed in a CaMV35S-ySpdSyn genotype, with fruits accumulating higher levels of the antioxidant lycopene. Notably, whole-plant senescence in the transgenic plants was also delayed compared with WT plants. Together, these results provide evidence for a role of PAs, particularly Spd, in increasing fruit shelf life, probably by reducing post-harvest senescence and decay. PMID- 20584150 TI - A plant DNA ligase is an important determinant of seed longevity. AB - DNA repair is important for maintaining genome integrity. In plants, DNA damage accumulated in the embryo of seeds is repaired early in imbibition, and is important for germination performance and seed longevity. An essential step in most repair pathways is the DNA ligase-mediated rejoining of single- and double strand breaks. Eukaryotes possess multiple DNA ligase enzymes, each having distinct roles in cellular metabolism. Here, we report the characterization of DNA LIGASE VI, which is only found in plant species. The primary structure of this ligase shows a unique N-terminal region that contains a beta-CASP motif, which is found in a number of repair proteins, including the DNA double-strand break (DSB) repair factor Artemis. Phenotypic analysis revealed a delay in the germination of atlig6 mutants compared with wild-type lines, and this delay becomes markedly exacerbated in the presence of the genotoxin menadione. Arabidopsis atlig6 and atlig6 atlig4 mutants display significant hypersensitivity to controlled seed ageing, resulting in delayed germination and reduced seed viability relative to wild-type lines. In addition, atlig6 and atlig6 atlig4 mutants display increased sensitivity to low-temperature stress, resulting in delayed germination and reduced seedling vigour upon transfer to standard growth conditions. Seeds display a rapid transcriptional DNA DSB response, which is activated in the earliest stages of water imbibition, providing evidence for the accumulation of cytotoxic DSBs in the quiescent seed. These results implicate AtLIG6 and AtLIG4 as major determinants of Arabidopsis seed quality and longevity. PMID- 20584151 TI - Reliability and validity of the Norwegian translation of the Child Eating Disorder Examination (ChEDE). AB - The Child Eating Disorder Examination (ChEDE) is a valid and reliable semi structured interview, which measures eating-disorder specific psychopathology in children and young adolescents. The instrument is an adaptation of version 12.0D of the original Eating Disorder Examination (EDE 12.0) for adults. The Norwegian translation of the ChEDE is currently the only instrument for assessing eating disorder psychopathology in Norwegian children and adolescents. This study aimed to investigate the psychometric properties of the Norwegian translation of the ChEDE 12.0. The Norwegian version of ChEDE 12.0 was administered to 15 Norwegian children with anorexia nervosa (AN), 15 children with diabetes mellitus type 1 (DM) and two groups of 15 age-matched controls. The groups were compared using a matched pairs design. The results showed that the subscale scores of the AN group were significantly higher than those of the other groups, and the DM comparison group did not differ from its control group. The current AN group scored significantly higher on the Shape Concern subscale than the previous UK sample, with implications for construct validity or cross-cultural effects worthy of further study. Inter-rater reliability was generally high (r=0.91 to 1.00), although there were significant differences between raters on specific items for individual participants. Alpha coefficients for each of the ChEDE subscales indicated a high degree of internal consistency. It was concluded that the Norwegian version of the ChEDE 12 has adequate psychometric properties and can be recommended for clinical and research use with young people with eating disorders in Norway. PMID- 20584152 TI - Associations of self-esteem and temperament traits to self- and teacher-reported social status among classmates. AB - The present study examined the validity of self- and teacher-reported social status and its relations to self-esteem and temperament in a geographically representative cohort of Finnish adolescents (N = 3941, mean age 15.1 years). High agreement was found between self- and teacher-rated social status (r = 0.42). Different aspects of self-esteem were differently related to social status. When other temperament and self-esteem variables were included in the analyses, strongest predictor for self-rated social status in both genders was social self-esteem (p < 0.01) and for teacher-rated social status general self esteem (p < 0.01). The strongest temperamental predictors of social status were lower inhibition in girls (p < 0.01, self- and teacher-rated) and higher impulsivity (p < 0.01, self-rated) and activity (p < 0.01, teacher-rated) in boys. The present findings are consistent with the view that social functioning and peer relations are associated with individual differences in self-concept and temperament dimensions. PMID- 20584153 TI - Rearing practices and impulsivity/hyperactivity symptoms in relation to inflated responsibility and obsessive-compulsive symptoms. AB - The aim of the study was to investigate potential precursors of inflated responsibility (responsibility attitudes) and obsessive-compulsive (OCD) symptoms. It was argued that both parental overprotection and impulsivity, separately and in interaction with each other, contribute to inflated responsibility and OCD symptoms. In a large sample of young adults (N = 570), self-report measures of OCD symptoms (OCI-R), responsibility attitudes (RAS), anxiety/depression (HADS), rearing practices (EMBU), present and past impulsivity/hyperactivity symptoms (IMP/HY) were administered. Overprotection as well as IMP/HY were found to predict OCD symptoms as well as inflated responsibility. Finally, a significant interaction was found between IMP/HY and overprotection with regard to both OCD symptoms and inflated responsibility. This effect reflected that IMP/HY was more strongly related to OCD symptoms and responsibility in people who had not been overprotected than in people who had been. Conversely overprotection was related to OCD symptoms and responsibility in people low but not in people high in IMP/HY. The results seem to indicate that the inadequacy between offer and need for parental control may play a role in the development of OCD symptoms. PMID- 20584154 TI - Kidney transplantation in a patient with congenital vena cava and right vena iliaca communis hypoplasia. PMID- 20584155 TI - Serum allergen-specific immunoglobulin E in atopic and healthy cats: comparison of a rapid screening immunoassay and complete-panel analysis. AB - Feline and canine atopic dermatitis are thought to have a similar immunopathogenesis. As with dogs, detection of allergen-specific IgE in cat serum merely supports a diagnosis of feline atopy based on compatible history, clinical signs and elimination of other pruritic dermatoses. In this study, a rapid screening immunoassay (Allercept((r)) E-Screen 2nd Generation; Heska AG, Fribourg, Switzerland; ES2G) was compared with a complete-panel serum allergen specific IgE assay (Allercept((r)); Heska AG; CP) in healthy cats with no history of skin disease and in atopic cats. The latter had no diagnosis of external parasitism, infection, food hypersensitivity or other skin disease explaining their pruritus, and expressed cutaneous reaction patterns typically associated with feline allergic skin disease (head, neck or pinnal pruritus, miliary dermatitis, self-induced alopecia, eosinophilic granuloma complex). The proportion of cats positive on either the ES2G or the CP assays was not significantly different between the atopic and healthy cat groups. There was, however, strong agreement between the results of the ES2G and CP assay; overall, the two tests were in agreement for 43 of 49 (88%) serum samples. There was also strong agreement when individual allergen groups were evaluated (agreement noted: indoor, 41 of 49 samples; grasses/weeds, 37 of 49 samples; and trees, 41 of 49 samples). These results indicate that although neither test is diagnostic for feline atopic dermatitis, the screening assay is beneficial for predicting the results of a complete-panel serum allergen-specific IgE assay in cats. PMID- 20584159 TI - The rickettsias and the bacteria formerly associated with the order Rickettsiales, namely, the genus Coxiella, are of major importance for the study of obligate intracellular microorganisms and their potential use as biological weapons. Preface. PMID- 20584161 TI - Results from a mathematical model for human monocytic ehrlichiosis. PMID- 20584160 TI - First evidence of Anaplasma infection in Crete, Greece. Report of six human cases. PMID- 20584162 TI - The prevalence of Anaplasma phagocytophilum in host-seeking Ixodes ricinus ticks in Norway. PMID- 20584163 TI - A 4-year study of Anaplasma phagocytophilum in Portugal. PMID- 20584164 TI - Anaplasma phagocytophilum propagation is enhanced in human complement-containing medium. PMID- 20584165 TI - Detection of Anaplasma phagocytophilum in wild boar in Slovenia. PMID- 20584166 TI - Molecular mechanism of gentamicin resistance in Bartonella henselae. PMID- 20584167 TI - Rickettsia spp. infection in Rhipicephalus sanguineus ticks in a Brazilian spotted fever endemic rural area in Rio de Janeiro state, Brazil. PMID- 20584168 TI - Transmission of Rickettsia sp. DmS1 in the tick, Dermacentor marginatus. PMID- 20584169 TI - Protracted speciation revitalizes the neutral theory of biodiversity. AB - Understanding the maintenance and origin of biodiversity is a formidable task, yet many ubiquitous ecological patterns are predicted by a surprisingly simple and widely studied neutral model that ignores functional differences between species. However, this model assumes that new species arise instantaneously as singletons and consequently makes unrealistic predictions about species lifetimes, speciation rates and number of rare species. Here, we resolve these anomalies - without compromising any of the original model's existing achievements and retaining computational and analytical tractability - by modelling speciation as a gradual, protracted, process rather than an instantaneous event. Our model also makes new predictions about the diversity of 'incipient' species and rare species in the metacommunity. We show that it is both necessary and straightforward to incorporate protracted speciation in future studies of neutral models, and argue that non-neutral models should also model speciation as a gradual process rather than an instantaneous one. PMID- 20584170 TI - Ecological competition favours cooperation in termite societies. AB - Conflict and competition lie at the heart of the theories of both ecology and sociobiology. Despite this, the interaction between societal conflicts on one hand and ecological competition on the other remains poorly understood. Here, we investigate this interaction in two ecologically similar sympatric termite species, Cryptotermes secundus Hill and Cryptotermes domesticus Haviland. We manipulated the incidence of king and queen loss (within-species conflict) and the incidence of cohabitation of the two species (between-species competition) in a series of 2 year experiments. Manipulation alone had no detectable effect and most colonies survived the 2-year period. In contrast, promoting both within- and between-species conflict caused the great majority of colonies to die. Moreover, the resulting colony loss was much more rapid in the conflict-ridden C. domesticus than in C. secundus. Our data suggest that ecological competition among species can greatly exacerbate the impact of internal conflicts, thereby promoting the evolution of within-species cooperation. PMID- 20584171 TI - Thromboangiitis obliterans and endothelial function. AB - BACKGROUND: Endothelial dysfunction may be involved in the pathophysiology of thromboangiitis obliterans (TAO). This study compares endothelial function and large artery stiffness between 10 TAO patients assessed during an exacerbation phase and 10 age- and sex-matched control subjects. MATERIAL AND METHODS: Flow mediated vasodilation after gradual hand skin heating (from 28 degrees C to 44 degrees C) and endothelium-independent vasodilation after sublingual administration of 150 microg glyceryl trinitrate (GTN) were studied using a high resolution echotracking system to simultaneously measure the brachial artery (BA) diameter and changes in wall shear stress. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity. RESULTS: The baseline BA diameter was significantly smaller in TAO patients (3599 +/- 668 microm) than in control subjects (4114 +/- 671, P = 0.04). Hand warming caused a linear increase in shear stress accompanied by a linear increase in BA diameter as a function of increasing temperature for TAO patients and control subjects. There was no significant difference between the two groups [relative increase in BA diameter: + 9.3% (-0.1 to 11.5) vs. + 4.8% (3.0 to 8.1), respectively; P = 0.63]. The slope of the BA diameter vs. shear stress relationship did not significantly differ between the two groups. The relative increase in the BA diameter after GTN was significantly greater in TAO patients than in controls [+ 30.8% (28.6 to 33.6) vs. + 16.2% (12.6 to 21.9) respectively; P = 0.02]. Finally, TAO patients had greater aortic stiffness than control subjects (9.81 +/- 1.72 m s(-1) vs. 7.82 +/ 0.84 m s(-1) respectively; P = 0.0052). CONCLUSIONS: Acute TAO is characterised by vasoconstriction and increased aortic stiffness in the absence of changes in flow-mediated dilation. PMID- 20584172 TI - Relationship of sFas with metabolic risk factors and their clusters. AB - BACKGROUND: Metabolic risk factors are known to cause atherosclerosis through inflammation. In the process of inflammation, soluble Fas (sFas) may interfere with the apoptotic pathway and contribute to dysregulated inflammation. Recent studies suggest sFas as a marker of inflammation in patients with cardiovascular diseases. However, whether a relationship exists between sFas levels and metabolic risk factors among healthy subjects remains unclear. MATERIALS AND METHODS: We measured the serum sFas levels of 876 subjects selected as controls for a nested case-control study within the JACC Study. The adjusted means of the sFas levels were compared according to the presence of overweight/obesity, hypertension, hyperlipidaemia, diabetes and their clusters. RESULTS: sFas level was significantly associated with overweight/obesity (2.42 ng mL(-1) in overweight/obese men and 2.19 in others) and hyperlipidaemia (2.34 ng mL(-1) in men with hyperlipidaemia and 2.19 in others) among men, though not with hypertension or diabetes. Moreover, a clear association between sFas levels and the cluster number of metabolic risk factors was observed independently with age, smoking and drinking(2.39, 2.28, 2.24 and 2.11 ng dL(-1) in men with three to four, two, one and none of the four metabolic risk factors respectively). However, among women, clear associations were not observed between sFas levels and the four metabolic risk factors or their clustering. CONCLUSIONS: Serum sFas levels appear to be associated with overweight/obesity, hyperlipidaemia and clusters of metabolic risk factors among men, suggesting that sFas may elevate to down-regulate increased apoptosis in atherogenesis processes. PMID- 20584173 TI - Making sense of multisensory integration. PMID- 20584174 TI - Semantic confusion regarding the development of multisensory integration: a practical solution. AB - There is now a good deal of data from neurophysiological studies in animals and behavioral studies in human infants regarding the development of multisensory processing capabilities. Although the conclusions drawn from these different datasets sometimes appear to conflict, many of the differences are due to the use of different terms to mean the same thing and, more problematic, the use of similar terms to mean different things. Semantic issues are pervasive in the field and complicate communication among groups using different methods to study similar issues. Achieving clarity of communication among different investigative groups is essential for each to make full use of the findings of others, and an important step in this direction is to identify areas of semantic confusion. In this way investigators can be encouraged to use terms whose meaning and underlying assumptions are unambiguous because they are commonly accepted. Although this issue is of obvious importance to the large and very rapidly growing number of researchers working on multisensory processes, it is perhaps even more important to the non-cognoscenti. Those who wish to benefit from the scholarship in this field but are unfamiliar with the issues identified here are most likely to be confused by semantic inconsistencies. The current discussion attempts to document some of the more problematic of these, begin a discussion about the nature of the confusion and suggest some possible solutions. PMID- 20584176 TI - Visuohaptic convergence in a corticocerebellar network. AB - The processing of visual and haptic inputs, occurring either separately or jointly, is crucial for everyday-life object recognition, and has been a focus of recent neuroimaging research. Previously, visuohaptic convergence has been mostly investigated with matching-task paradigms. However, much less is known about visuohaptic convergence in the absence of additional task demands. We conducted two functional magnetic resonance imaging experiments in which subjects actively touched and/or viewed unfamiliar object stimuli without any additional task demands. In addition, we performed two control experiments with audiovisual and audiohaptic stimulation to examine the specificity of the observed visuohaptic convergence effects. We found robust visuohaptic convergence in bilateral lateral occipital cortex and anterior cerebellum. In contrast, neither the anterior cerebellum nor the lateral occipital cortex showed any involvement in audiovisual or audiohaptic convergence, indicating that multisensory convergence in these regions is specifically geared to visual and haptic inputs. These data suggest that in humans the lateral occipital cortex and the anterior cerebellum play an important role in visuohaptic processing even in the absence of additional task demands. PMID- 20584175 TI - Visual-vestibular cue integration for heading perception: applications of optimal cue integration theory. AB - The perception of self-motion is crucial for navigation, spatial orientation and motor control. In particular, estimation of one's direction of translation, or heading, relies heavily on multisensory integration in most natural situations. Visual and nonvisual (e.g., vestibular) information can be used to judge heading, but each modality alone is often insufficient for accurate performance. It is not surprising, then, that visual and vestibular signals converge frequently in the nervous system, and that these signals interact in powerful ways at the level of behavior and perception. Early behavioral studies of visual-vestibular interactions consisted mainly of descriptive accounts of perceptual illusions and qualitative estimation tasks, often with conflicting results. In contrast, cue integration research in other modalities has benefited from the application of rigorous psychophysical techniques, guided by normative models that rest on the foundation of ideal-observer analysis and Bayesian decision theory. Here we review recent experiments that have attempted to harness these so-called optimal cue integration models for the study of self-motion perception. Some of these studies used nonhuman primate subjects, enabling direct comparisons between behavioral performance and simultaneously recorded neuronal activity. The results indicate that humans and monkeys can integrate visual and vestibular heading cues in a manner consistent with optimal integration theory, and that single neurons in the dorsal medial superior temporal area show striking correlates of the behavioral effects. This line of research and other applications of normative cue combination models should continue to shed light on mechanisms of self-motion perception and the neuronal basis of multisensory integration. PMID- 20584177 TI - Staying within the lines: the formation of visuospatial boundaries influences multisensory feature integration. AB - The brain processes multisensory features of an object (e.g., its sound and shape) in separate cortical regions. A key question is how representations of these features bind together to form a coherent percept (the 'binding problem'). Here we tested the hypothesis that the determination of an object's visuospatial boundaries is paramount to the linking of its multisensory features (i.e., that the refinement of attended space through the formation of visual boundaries establishes the boundaries for multisensory feature integration). We recorded both scalp and intracranial electrophysiological data in response to Kanizsa-type illusory contour stimuli (in which pacman-like elements give the impression of a single object), their non-illusory counterparts, and auditory stimuli. Participants performed a visual task and ignored sounds. Enhanced processing of task-irrelevant sounds when paired with attended visual stimuli served as our metric for multisensory feature integration [e.g., Busse et al. (2005) Proc. Natl Acad. Sci. USA 102: 18751-18756]. According to our hypothesis, task-irrelevant sounds paired with Kanizsa-type illusory contour stimuli (which have well-defined boundaries) should receive enhanced processing relative to task-irrelevant sounds paired with non-illusory contour stimuli (which have ambiguous boundaries). The scalp data clearly support this prediction and, combined with the intracranial data, advocate for an important extension of models for multisensory feature integration. We propose a model in which (i) the visual boundaries of an object are established through processing in occipitotemporal cortex, and (ii) attention then spreads to cortical regions that process features that fall within the object's established visual boundaries, including its task-irrelevant multisensory features. PMID- 20584178 TI - The electrophysiological time course of the interaction of stimulus conflict and the multisensory spread of attention. AB - Previously, we have shown that spatial attention to a visual stimulus can spread across both space and modality to a synchronously presented but task-irrelevant sound arising from a different location, reflected by a late-onsetting, sustained, negative-polarity event-related potential (ERP) wave over frontal central scalp sites, probably originating in part from the auditory cortices. Here we explore the influence of cross-modal conflict on the amplitude and temporal dynamics of this multisensory spreading-of-attention activity. Subjects attended selectively to one of two concurrently presented lateral visually presented letter streams to perform a sequential comparison task, while ignoring task-irrelevant, centrally presented spoken letters that could occur synchronously with either the attended or unattended lateral visual letters and could be either congruent or incongruent with them. Extracted auditory ERPs revealed that, collapsed across congruency conditions, attentional spreading across modalities started at approximately 220 ms, replicating our earlier findings. The interaction between attentional spreading and conflict occurred beginning at approximately 300 ms, with attentional-spreading activity being larger for incongruent trials. Thus, the increased processing of an incongruent, task-irrelevant sound in a multisensory stimulation appeared to occur some time after attention has spread from the attended visual part to the ignored auditory part, presumably reflecting the conflict detection and associated attentional capture requiring accrual of some multisensory interaction processes at a higher level semantic processing stage. PMID- 20584179 TI - Attention regulates the plasticity of multisensory timing. AB - Evidence suggests than human time perception is likely to reflect an ensemble of recent temporal experience. For example, prolonged exposure to consistent temporal patterns can adaptively realign the perception of event order, both within and between sensory modalities (e.g. Fujisaki et al., 2004 Nat. Neurosci., 7, 773-778). In addition, the observation that 'a watched pot never boils' serves to illustrate the fact that dynamic shifts in our attentional state can also produce marked distortions in our temporal estimates. In the current study we provide evidence for a hitherto unknown link between adaptation, temporal perception and our attentional state. We show that our ability to use recent sensory history as a perceptual baseline for ongoing temporal judgments is subject to striking top-down modulation via shifts in the observer's selective attention. Specifically, attending to the temporal structure of asynchronous auditory and visual adapting stimuli generates a substantial increase in the temporal recalibration induced by these stimuli. We propose a conceptual framework accounting for our findings whereby attention modulates the perceived salience of temporal patterns. This heightened salience allows the formation of audiovisual perceptual 'objects', defined solely by their temporal structure. Repeated exposure to these objects induces high-level pattern adaptation effects, akin to those found in visual and auditory domains (e.g. Leopold & Bondar (2005) Fitting the Mind to the World: Adaptation and Aftereffects in High-Level Vision. Oxford University Press, Oxford, 189-211; Schweinberger et al. (2008) Curr. Biol., 18, 684-688). PMID- 20584180 TI - Acquired prior knowledge modulates audiovisual integration. AB - Orienting responses to audiovisual events in the environment can benefit markedly by the integration of visual and auditory spatial information. However, logically, audiovisual integration would only be considered successful for stimuli that are spatially and temporally aligned, as these would be emitted by a single object in space-time. As humans do not have prior knowledge about whether novel auditory and visual events do indeed emanate from the same object, such information needs to be extracted from a variety of sources. For example, expectation about alignment or misalignment could modulate the strength of multisensory integration. If evidence from previous trials would repeatedly favour aligned audiovisual inputs, the internal state might also assume alignment for the next trial, and hence react to a new audiovisual event as if it were aligned. To test for such a strategy, subjects oriented a head-fixed pointer as fast as possible to a visual flash that was consistently paired, though not always spatially aligned, with a co-occurring broadband sound. We varied the probability of audiovisual alignment between experiments. Reaction times were consistently lower in blocks containing only aligned audiovisual stimuli than in blocks also containing pseudorandomly presented spatially disparate stimuli. Results demonstrate dynamic updating of the subject's prior expectation of audiovisual congruency. We discuss a model of prior probability estimation to explain the results. PMID- 20584181 TI - Onset timing of cross-sensory activations and multisensory interactions in auditory and visual sensory cortices. AB - Here we report early cross-sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300-ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within-modality and cross-sensory activations. fMRI cross sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects the influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl's gyrus) the onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross-sensory activations thus started later than sensory-specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross-sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30-35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory and 74 ms in the visual cortex, i.e., 3-21 ms after inputs from the two modalities converged. PMID- 20584183 TI - Independent mechanisms for ventriloquism and multisensory integration as revealed by theta-burst stimulation. AB - The visual and auditory systems often concur to create a unified perceptual experience and to determine the localization of objects in the external world. Co occurring auditory and visual stimuli in spatial coincidence are known to enhance performance of auditory localization due to the integration of stimuli from different sensory channels (i.e. multisensory integration). However, auditory localization of audiovisual stimuli presented at spatial disparity might also induce a mislocalization of the sound towards the visual stimulus (i.e. ventriloquism effect). Using repetitive transcranial magnetic stimulation we tested the role of right temporoparietal (rTPC), right occipital (rOC) and right posterior parietal (rPPC) cortex in an auditory localization task in which indices of ventriloquism and multisensory integration were computed. We found that suppression of rTPC excitability by means of continuous theta-burst stimulation (cTBS) reduced multisensory integration. No similar effect was found for cTBS over rOC. Moreover, inhibition of rOC, but not of rTPC, suppressed the visual bias in the contralateral hemifield. In contrast, cTBS over rPPC did not produce any modulation of ventriloquism or integrative effects. The double dissociation found in the present study suggests that ventriloquism and audiovisual multisensory integration are functionally independent phenomena and may be underpinned by partially different neural circuits. PMID- 20584182 TI - TMS of posterior parietal cortex disrupts visual tactile multisensory integration. AB - Functional neuroimaging studies have implicated a number of brain regions, especially the posterior parietal cortex (PPC), as being potentially important for visual-tactile multisensory integration. However, neuroimaging studies are correlational and do not prove the necessity of a region for the behavioral improvements that are the hallmark of multisensory integration. To remedy this knowledge gap, we interrupted activity in the PPC, near the junction of the anterior intraparietal sulcus and the postcentral sulcus, using MRI-guided transcranial magnetic stimulation (TMS) while subjects localized touches delivered to different fingers. As the touches were delivered, subjects viewed a congruent touch video, an incongruent touch video, or no video. Without TMS, a strong effect of multisensory integration was observed, with significantly better behavioral performance for discrimination of congruent multisensory touch than for unisensory touch alone. Incongruent multisensory touch produced a smaller improvement in behavioral performance. TMS of the PPC eliminated the behavioral advantage of both congruent and incongruent multisensory stimuli, reducing performance to unisensory levels. These results demonstrate a causal role for the PPC in visual-tactile multisensory integration. Taken together with converging evidence from other studies, these results support a model in which the PPC contains a map of space around the hand that receives input from both the visual and somatosensory modalities. Activity in this map is likely to be the neural substrate for visual-tactile multisensory integration. PMID- 20584184 TI - Enhancing multisensory spatial orienting by brain polarization of the parietal cortex. AB - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces polarity-specific excitability changes in the human brain, therefore altering physiological, perceptual and higher-order cognitive processes. Here we investigated the possibility of enhancing attentional orienting within and across different sensory modalities, namely visual and auditory, by polarization of the posterior parietal cortex (PPC), given the putative involvement of this area in both unisensory and multisensory spatial processing. In different experiments, we applied anodal or sham tDCS to the right PPC and, for control, anodal stimulation of the right occipital cortex. Using a redundant signal effect (RSE) task, we found that anodal tDCS over the right PPC significantly speeded up responses to contralateral targets, regardless of the stimulus modality. Furthermore, the effect was dependant on the nature of the audiovisual enhancement, being stronger when subserved by a probabilistic mechanism induced by blue visual stimuli, which probably involves processing in the PPC. Hence, up-regulating the level of excitability in the PPC by tDCS appears a successful approach for enhancing spatial orienting to unisensory and crossmodal stimuli. Moreover, audiovisual interactions mostly occurring at a cortical level can be selectively enhanced by anodal PPC tDCS, whereas multisensory integration of stimuli, which is also largely mediated at a subcortical level, appears less susceptible to polarization of the cortex. PMID- 20584186 TI - Neuromagnetic oscillations to emotional faces and prosody. AB - Higher association cortices as well as unisensory areas can support multisensory integration [D. Senkowski et al. (2008) Trends Neurosci., 31, 401-409]. The present study investigated whether audiovisual integration of emotional information emerges early at unisensory or later at higher association cortices. Emotional stimuli were presented in three blocks: audiovisual (AV), auditory (A) and visual (V). Eighteen participants performed a delayed emotional recognition task (happy, angry or neutral prosody and/or facial expression) while whole-brain magnetoencephalography (MEG) data were obtained. Time-frequency evoked and total power analyses were performed on the sensor data, and source localization of the frequencies of interest performed via a synthetic aperture magnetometry beamformer. To examine crossmodal integration between bimodal and unimodal conditions, two contrasts were specified: AV > A and AV > V. In the AV > A contrast, early effects were observed on both the temporal and the occipital evoked responses. However, at the source level, early alpha suppression was limited to the occipital sources without changes in temporal cortices. In the AV > V contrast, sensor and source findings revealed increased alpha suppression only in temporal cortices, with no changes in visual cortex. Thus, no crossmodal effect in unisensory areas emerged. Instead, increased frontal alpha activity in both the AV > A and AV > V contrasts supports the view that affective information from face and prosody converges at higher association cortices. PMID- 20584187 TI - Multisensory cues improve sensorimotor synchronisation. AB - Synchronising movements with events in the surrounding environment is an ubiquitous aspect of everyday behaviour. Often, information about a stream of events is available across sensory modalities. While it is clear that we synchronise more accurately to auditory cues than other modalities, little is known about how the brain combines multisensory signals to produce accurately timed actions. Here, we investigate multisensory integration for sensorimotor synchronisation. We extend the prevailing linear phase correction model for movement synchronisation, describing asynchrony variance in terms of sensory, motor and timekeeper components. Then we assess multisensory cue integration, deriving predictions based on the optimal combination of event time, defined across different sensory modalities. Participants tapped in time with metronomes presented via auditory, visual and tactile modalities, under either unimodal or bimodal presentation conditions. Temporal regularity was manipulated between modalities by applying jitter to one of the metronomes. Results matched the model predictions closely for all except high jitter level conditions in audio-visual and audio-tactile combinations, where a bias for auditory signals was observed. We suggest that, in the production of repetitive timed actions, cues are optimally integrated in terms of both sensory and temporal reliability of events. However, when temporal discrepancy between cues is high they are treated independently, with movements timed to the cue with the highest sensory reliability. PMID- 20584185 TI - Dynamic, rhythmic facial expressions and the superior temporal sulcus of macaque monkeys: implications for the evolution of audiovisual speech. AB - Audiovisual speech has a stereotypical rhythm that is between 2 and 7 Hz, and deviations from this frequency range in either modality reduce intelligibility. Understanding how audiovisual speech evolved requires investigating the origins of this rhythmic structure. One hypothesis is that the rhythm of speech evolved through the modification of some pre-existing cyclical jaw movements in a primate ancestor. We tested this hypothesis by investigating the temporal structure of lipsmacks and teeth-grinds of macaque monkeys and the neural responses to these facial gestures in the superior temporal sulcus (STS), a region implicated in the processing of audiovisual communication signals in both humans and monkeys. We found that both lipsmacks and teeth-grinds have consistent but distinct peak frequencies and that both fall well within the 2-7 Hz range of mouth movements associated with audiovisual speech. Single neurons and local field potentials of the STS of monkeys readily responded to such facial rhythms, but also responded just as robustly to yawns, a nonrhythmic but dynamic facial expression. All expressions elicited enhanced power in the delta (0-3Hz), theta (3-8Hz), alpha (8 14Hz) and gamma (> 60 Hz) frequency ranges, and suppressed power in the beta (20 40Hz) range. Thus, STS is sensitive to, but not selective for, rhythmic facial gestures. Taken together, these data provide support for the idea that that audiovisual speech evolved (at least in part) from the rhythmic facial gestures of an ancestral primate and that the STS was sensitive to and thus 'prepared' for the advent of rhythmic audiovisual communication. PMID- 20584188 TI - Observing touch activates human primary somatosensory cortex. AB - We used magnetoencephalography to show that the human primary somatosensory (SI) cortex is activated by mere observation of touch. Somatosensory evoked fields were measured from adult human subjects in two conditions. First, the experimenter touched the subject's right hand with her index finger (Experienced touch). In the second condition, the experimenter touched her own hand in a similar manner (Observed touch). Minimum current estimates were computed across three consecutive 300-ms time windows (0-300, 300-600 and 600-900 ms) with respect to touch onset. During 'Experienced touch', as expected, the contralateral (left) SI cortex was strongly activated in the 0-300 ms time window. In the same time window, statistically significant activity also occurred in the ipsilateral SI, although it was only 2.5% of the strength of the contralateral activation; the ipsilateral activation continued in the 300-600 ms time window. During 'Observed touch', the left SI cortex was activated during the 300-600 ms interval; the activation strength was 7.5% of that during the significantly activated period (0-300 ms) of 'Experienced touch'. The results suggest that when people observe somebody else being touched, activation of their own somatosensory circuitry may contribute to understanding of the other person's somatosensory experience. PMID- 20584189 TI - Tactile capture of auditory localization: an event-related potential study. AB - The well-known ventriloquist illusion arises when sounds are mislocalized towards a synchronous but spatially discrepant visual stimulus, and a similar effect of touch on audition has also been reported. By manipulating hand position, we recently demonstrated that this audiotactile ventriloquism effect predominantly operates in an external coordinate system. Using event-related potentials, the present study investigated the neural correlates of this audiotactile ventriloquism effect. Participants reported the perceived location of brief auditory stimuli that were presented either alone or with concurrent tactile stimuli to the fingertips, which were situated at the left and right side of the speaker array. Concurrent electroencephalogram recordings suggested a biasing of cortical activity by the tactile stimuli, which was only observed for trials in which a ventriloquist illusion was elicited. Irrespective of the physical location of the sound source in the bimodal trials, centrally perceived sounds elicited an enhanced centrally distributed negativity, compared to laterally perceived sounds, between 260 and 400 ms following stimulus onset, similar to unimodal auditory stimuli that were actually presented from central and lateral positions, respectively. Moreover, this effect was modulated by hand posture. When external and anatomically centred reference frames were in conflict, the event-related potential effect was reduced for small audiotactile spatial discrepancies, which corresponded to the behavioural finding of a reduced audiotactile ventriloquism effect compared to a parallel hand posture. The present data suggest that the cortical representation of auditory space is adjusted to coincide with spatially disparate tactile input. PMID- 20584190 TI - Tactile remapping beyond space. AB - Reacting to a touch on the skin often requires the remapping of the initial somatotopicaly-based representation of the stimulus into an external frame of reference that incorporates information about current body posture. A growing number of studies support the view that tactile encoding in external coordinates occurs automatically. However, it remains unclear whether or not spatial task demands are required to trigger this remapping process, casting some doubt on the automaticity hypothesis. We designed three experiments in which space was progressively removed, and tactile remapping across different body postures was gauged through the modulation of visual performance. We used speeded two alternative forced-choice colour judgements (i.e., a nonspatial selection feature) about visual targets presented laterally following a spatially noninformative (congruent or incongruent) tactile cue on one hand. In experiment 1, using footpedal responses, visual performance was modulated according to the external location of the tactile cue, regardless of hand posture (either crossed or uncrossed). In experiment 2, using verbal responses, external cueing was also observed (albeit in an attenuated fashion) despite the removal of space from response set. In experiment 3 we removed spatial uncertainty about cue and target locations by presenting tactile cues and visual targets from fixed positions, yet spatial congruency still exerted some modulation on visual performance, again independent of hand posture. These results demonstrate that engaging in spatial tasks is not a prerequisite for triggering tactile remapping, and are thus in agreement with previous accounts suggesting that touch is automatically remapped. PMID- 20584191 TI - Seeing the body modulates audiotactile integration. AB - Audiotactile integration has been studied using various experimental setups but so far crossmodal congruency effects (CCEs) have not been found for tactile targets paired with auditory distractors. In the present study we investigated whether audiotactile CCEs exist and, if so, whether these CCEs have similar characteristics to those found by previous authors with visual distractors. We measured audiotactile CCEs by attaching four vibrators to the backs of participants and presented auditory stimuli from four loudspeakers placed, in separate blocks, at different distances in front of or behind the participant's body. Participants discriminated the elevation of tactile stimuli while ignoring the auditory distractors. CCEs were found only when participants were provided with noninformative vision of their own body, as seen from behind via a camera and head-mounted display; they were absent when participants did not view their body. Furthermore, in contrast to visuotactile CCEs, audiotactile CCEs did not depend on whether the distractors were presented on the same or different side as the tactile targets. The present study provides the first demonstration of an audiotactile CCE: incongruent auditory distractors impaired performance on a tactile elevation discrimination task relative to performance with congruent distractors. We show that audiotactile CCEs differ from visuotactile CCEs as they do not appear to be as sensitive to the spatial relations between the distractors and the tactile stimuli. We also show that these CCEs are modulated by vision of the body. PMID- 20584192 TI - Which finger? Early effects of attentional selection within the hand are absent when the hand is viewed. AB - The sight of a hand can bias the distribution of spatial attention, and recently it has been shown that viewing both hands simultaneously can facilitate spatial selection between tactile events at the hands when these are far apart. Here we directly compared the electrophysiological correlates of within-hand and between hands tactile-spatial selection to investigate whether within-hand selection is similarly facilitated by viewing the fingers. Using somatosensory event-related potentials, we have shown that effects of selection between adjacent fingers of the same hand at early somatosensory components P45 and N80 were absent when the fingers were viewed. Thus, we found a detrimental effect of vision on tactile spatial within-body part (i.e. hand) selection. In contrast, effects of tactile spatial selection between hands placed next to each other, which were first found at the P100 component, were unaffected by vision of the hands. Our findings suggest that (i) within-hand and between-hands selection can operate at different stages of processing, and (ii) the effects of vision on within-hand and between hands attentional selection may reflect fundamentally different mechanisms. PMID- 20584193 TI - Are surface properties integrated into visuohaptic object representations? AB - Object recognition studies have almost exclusively involved vision, focusing on shape rather than surface properties such as color. Visual object representations are thought to integrate shape and color information because changing the color of studied objects impairs their subsequent recognition. However, little is known about integration of surface properties into visuohaptic multisensory representations. Here, participants studied objects with distinct patterns of surface properties (color in Experiment 1, texture in Experiments 2 and 3) and had to discriminate between object shapes when color or texture schemes were altered in within-modal (visual and haptic) and cross-modal (visual study followed by haptic test and vice versa) conditions. In Experiment 1, color changes impaired within-modal visual recognition but had no effect on cross-modal recognition, suggesting that the multisensory representation was not influenced by modality-specific surface properties. In Experiment 2, texture changes impaired recognition in all conditions, suggesting that both unisensory and multisensory representations integrated modality-independent surface properties. However, the cross-modal impairment might have reflected either the texture change or a failure to form the multisensory representation. Experiment 3 attempted to distinguish between these possibilities by combining changes in texture with changes in orientation, taking advantage of the known view independence of the multisensory representation, but the results were not conclusive owing to the overwhelming effect of texture change. The simplest account is that the multisensory representation integrates shape and modality independent surface properties. However, more work is required to investigate this and the conditions under which multisensory integration of structural and surface properties occurs. PMID- 20584194 TI - The brain weights body-based cues higher than vision when estimating walked distances. AB - Optic flow is the stream of retinal information generated when an observer's body, head or eyes move relative to their environment, and it plays a defining role in many influential theories of active perception. Traditionally, studies of optic flow have used artificially generated flow in the absence of the body-based cues typically coincident with self-motion (e.g. proprioceptive, efference copy, and vestibular). While optic flow alone can be used to judge the direction, speed and magnitude of self-motion, little is known about the precise extent to which it is used during natural locomotor behaviours such as walking. In this study, walked distances were estimated in an open outdoor environment. This study employed two novel complementary techniques to dissociate the contributions of optic flow from body-based cues when estimating distance travelled in a flat, open, outdoor environment void of distinct proximal visual landmarks. First, lenses were used to magnify or minify the visual environment. Second, two walked distances were presented in succession and were either the same or different in magnitude; vision was either present or absent in each. A computational model was developed based on the results of both experiments. Highly convergent cue weighting values were observed, indicating that the brain consistently weighted body-based cues about twice as high as optic flow, the combination of the two cues being additive. The current experiments represent some of the first to isolate and quantify the contributions of optic flow during natural human locomotor behaviour. PMID- 20584195 TI - Multisensory determinants of orientation perception: task-specific sex differences. AB - Females have been reported to be more 'visually dependent' than males. When aligning a rod in a tilted frame to vertical, females are more influenced by the frame than are males, who align the rod closer to gravity. Do females rely more on visual information at the cost of other sensory information? We compared the subjective visual vertical and the perceptual upright in 29 females and 24 males. The orientation of visual cues presented on a shrouded laptop screen and of the observer's posture were varied. When upright, females' subjective visual vertical was more influenced by visual cues and their responses were more variable than were males'. However, there were no differences between the sexes in the perceptual upright task. Individual variance in subjective visual vertical judgments and in the perceptual upright predicted the level of visual dependence across both sexes. When lying right-side down, there were no reliable differences between the sexes in either measure. We conclude that heightened 'visual dependence' in females does not generalize to all aspects of spatial processing but is probably attributable to task-specific differences in the mechanisms of sensory processing in the brains of females and males. The higher variability and lower accuracy in females for some spatial tasks is not due to their having qualitatively worse access to information concerning either the gravity axis or corporeal representation: it is only when gravity and the long body axis align that females have a performance disadvantage. PMID- 20584196 TI - Sensory-specific clock components and memory mechanisms: investigation with parallel timing. AB - A challenge for researchers in the time-perception field is to determine whether temporal processing is governed by a central mechanism or by multiple mechanisms working in concert. Behavioral studies of parallel timing offer interesting insights into the question, although the conclusions fail to converge. Most of these studies focus on the number-of-clocks issue, but the commonality of memory mechanisms involved in time processing is often neglected. The present experiment aims to address a straightforward question: do signals from different modalities marking time intervals share the same clock and/or the same memory resources? To this end, an interval reproduction task involving the parallel timing of two sensory signals presented either in the same modality or in different modalities was conducted. The memory component was tested by manipulating the delay separating the presentation of the target intervals and the moment when the reproduction of one of these began. Results show that there is more variance when only visually marked intervals are presented, and this effect is exacerbated with longer retention delays. Finally, when there is only one interval to process, encoding the interval with signals delivered from two modalities helps to reduce variance. Taken together, these results suggest that the hypothesis stating that there are sensory-specific clock components and memory mechanisms is viable. PMID- 20584197 TI - Prevalence of the MspI and Ile462Val SNPs of cytochrome P-450 1A1 in hidradenitis suppurativa. AB - Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that affects the hair follicles in the axillary, perianal and inguinal area. Its cause and pathogenesis are unknown, but cigarette smoking increases the risk of developing HS conceivably by accumulating toxic metabolites in sweat. The xenobiotic compounds from tobacco are metabolized by the cytochromes P-450. The cytochrome P 450 1A1 (CYP1A1), one of the most active isoenzymes, harbours several polymorphisms. Two of them, MspI and Ile(462)Val single nucleotide polymorphism (SNP), are associated with enhanced activity and inducibility. Performing direct DNA sequencing, we investigated the frequencies of these SNP in 51 patients with HS, 45 of these were smokers. We found similar overall SNP rates in our patients in comparison with previous data for Caucasian or German controls. Obviously, there is no relation between the occurrence of these SNPs and the risk of developing HS. PMID- 20584199 TI - Inhibition of the diclofenac-induced cyclooxygenase-2 activity by paracetamol in cultured macrophages is not related to the intracellular lipid hydroperoxide tone. AB - Paracetamol, a weak inhibitor of cyclooxygenase COX-1 and COX-2 activities, has been reported to inhibit the activity of COX-2 induced by diclofenac in J774.2 macrophage cell line. The lack of inhibition of COX-2 by paracetamol in inflamed tissues and thereby the lack of anti-inflammatory activity has been attributed to high lipid hydroperoxide (LHP) tone. In this study, we demonstrate that the inhibition of the diclofenac-induced COX-2 activity in J774.2 cells by paracetamol is not related to the intracellular LHP tone as paracetamol inhibited this activity in the absence and presence of T-butyl hydroperoxide, which is an LHP donor, to the same extents. In fact, treatment of the cells with diclofenac resulted in an increase in the LHP tone. Stimulation of the cells with lipopolysaccharide (LPS) results in the induction of a COX-2 activity, which was not inhibited by paracetamol. This represents the classical induction pathway for COX-2. LPS stimulation did not alter the LHP tone. These results suggest that the enzymatic activity of the diclofenac-induced COX-2 protein does not depend on the supply of hydroperoxides to its peroxidase active site. PMID- 20584200 TI - Neuropharmacological effects of lipoic acid and ubiquinone on delta aminolevulinic dehydratase, Na(+) , K(+) -ATPase, and Mg(2+) -ATPase activities in rat hippocampus after pilocarpine-induced seizures. AB - In this study, we investigated the effects of lipoic acid (LA) in the hippocampus oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10mg/kg, i.p., LA group), ubiquinone [20mg/kg, i.p., ubiquinone (UQ) group], pilocarpine (400mg/kg, i.p., P400 group), and the association of LA (10mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.) or UQ (20mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.), 30min before of administration of P400 (LA plus P400 group and UQ plus P400 group, respectively). After the treatments, all groups were observed for 1h. The enzyme activities (delta-aminolevulinic dehydratase (delta-ALA-D), Mg(2+) -ATPase, and Na(+) , K(+) -ATPase) were measured using spectrophotometric methods, and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA and UQ were also evaluated on the same parameters. We reported here for the first time that Na(+) , K(+) -ATPase and delta-ALA-D activities inhibition and Mg(2+) -ATPase stimulation in the pilocarpine model are probably attributed to the oxidative stress caused by seizures in the rat hippocampus. The addition of the antioxidants LA and UQ may reverses the previously mentioned Na(+) , K(+) -ATPase and delta-ALA-D inhibitions and Mg(2+) ATPase stimulation. CONCLUSIONS: The oxidative stress plays an important signaling role in pilocarpine-induced seizures, and antioxidant drugs might be considered as therapeutical tools in this pathology. PMID- 20584201 TI - Fixed-dose combinations for cough and common cold in India: an assessment of availability and rationality. AB - This study was conducted to determine the number and composition of the various cough and cold formulations available in the Indian market and to study their pharmacological rationale over a period of 7years. Data for the study was collected from an annual Drug Compendium entitled 'THE DRUG TODAY' of the years 2001, 2004, and 2007. Medications were assessed for total number, different formulations, and number of constituents present in each formulation, their pharmacological group and amount of each constituent per dose. Rationality of available preparations was assessed on a seven-point scoring criteria. There are over thirteen hundred drug products for cough and cold in the Indian market, which is an increase of 71.2% from the year 2001. More than 90% of the preparations were fixed-dose combinations (FDCs). Majority of the cough and cold preparations had 3-4 constituents. Many preparations contained more than one constituent of the same pharmacological group. Some preparations had constituents with opposing action. A wide variation in the amount of each constituent present per dose in different formulations was observed. The number of banned drug combinations for cough and cold showed an increase from 9 in 2001 to 27 in 2007. Rationality assessment of the FDC preparations revealed that most of the preparations were irrational and had no documented benefit in the treatment of common cold. Availability of such a large number of irrational FDCs for cough and cold requires serious review of the legal provisions in India for drug manufacturing and marketing. PMID- 20584202 TI - Reduced cardiac remodelling and prevention of glutathione deficiency after omega 3 supplementation in chronic heart failure. AB - n-3 polyunsaturated fatty acids (omega-3) supplementation is associated with reduced cardiovascular mortality and post-infarction death. However, the impact of omega-3 supplementation in congestive heart failure (CHF) is still unknown. This study assesses the effects of omega-3 supplementation on left ventricular (LV) function and remodelling. We assessed, in rats with CHF induced by left coronary ligation, the effects of a 1-week and a 12-week supplementation with omega-3 (450 mg/kg per day) on LV hemodynamics, function and structure. Chronic omega-3 reduces total peripheral resistance due to an increase in cardiac output without modification of arterial pressure. Only chronic omega-3 reduces LV end diastolic pressure and LV relaxation constant. Moreover, chronic omega-3 decreases LV systolic and diastolic diameters, LV weight and collagen density. Acute and chronic omega-3 increase LV gamma-glutamyl-cysteine synthetase and oppose glutathione deficiency resulting in a reduction of myocardial oxidized glutathione. In experimental CHF, long-term omega-3 supplementation improves LV hemodynamics and function and prevents LV remodelling and glutathione deficiency. The latter might be one of the mechanisms involved, but whether other mechanism, independent of myocardial redox 'status', such as reduced inflammation, are implicated remains to be confirmed. PMID- 20584203 TI - Neuropharmacological effects of lipoic acid and ubiquinone on the mRNA level of interleukin-1beta and acetylcholinesterase activity in rat hippocampus after seizures. AB - The purpose of this study was to investigate the neuroprotective effects of lipoic acid and ubiquinone on interleukin-1beta (IL-1beta) mRNA levels and acetylcholinesterase (AChE) activities in rat hippocampus after pilocarpine induced seizures. Wistar rats were intraperitoneally administered with either 0.9% saline (icontrol group), LA (10 or 20 mg/kg, LA10 or LA20 groups), UQ (20 or 40 mg/kg, UQ20 and UQ40 groups), pilocarpine (400 mg/kg, P400 group), or co administration of pilocarpine with LA or UQ groups 30 min prior to LA or UQ administration. After the treatments, all groups were observed for 1 h. IL-1beta mRNA and AChE activity in rat hippocampus at 1 h after SE onset was determined. Results showed that rats pretreated with LA or UQ developed less seizures and SE more slowly and has less number than animals treated with pilocarpine alone. Reduced IL-1beta mRNA and marked AChE activities in the hippocampus were significantly higher in rats pretreated with LA or UQ in comparison with the values of the control and seized groups. Our findings strongly support the hypothesis that an increase on IL-1beta mRNA levels in hippocampus occurs during seizures induced by pilocarpine, which indicates that inflammatory process plays a crucial role in seizures pathogenic consequences. Our result also suggests that LA or UQ can exert significant neuroprotective effects, at least in part, because of the increase in the AChE activities in rat hippocampus that will be useful in the treatment of neurodegenerative diseases. PMID- 20584204 TI - Management of acute coronary syndromes from a gender perspective. AB - Acute Coronary Syndromes are the most frequent manifestations of coronary heart disease (CHD). Gender differences in treatment intensity, including differences in level of care, have been reported. Also differences in benefit from certain treatments, especially invasive treatment, have been discussed. Finally, differences in outcome between men and women have been proposed. Results have been inconsistent, partly depending on if and how adjustment for differences in background characteristics has been made. PMID- 20584205 TI - Role of catecholamine oxidation in sudden cardiac death. AB - Although sudden cardiac death is a leading cause of mortality, the mechanisms for its pathogenesis are poorly understood. Because overactivation of sympathetic nervous system is invariably seen in subjects with high risk for sudden cardiac death, elevated levels of circulating catecholamine levels are considered to result in lethal ventricular arrhythmias and subsequent sudden cardiac death. Such arrhythmogenic effects of catecholamines are generally believed to occur by their actions on alpha-adrenoceptors in coronary arteries for inducing coronary spasm and subsequent myocardial ischemia as well as on beta-adrenoceptors in cardiomyocytes for increasing the concentration of cyclic AMP excessively and producing defects in intracellular Ca2+ handling. Experimental evidence from our laboratory has revealed that excessive amounts of circulating catecholamines are oxidized to aminochromes, which are highly reactive quinine compounds. The oxidation products of catecholamines have been demonstrated to produce subcellular alterations, intracellular Ca2+ overload, coronary spasm, myocardial cell damage, depletion of high energy stores, and ventricular arrhythmias. In addition, oxyradicals, which are known to generate oxidative stress and produce cardiotoxic effects, including arrhythmias, are formed during the oxidation of catecholamines. Accordingly, it is proposed that oxidation of catecholamines and the generation of oxidative stress under stressful conditions may play a critical role in the genesis of ventricular arrhythmias that may result in sudden cardiac death. PMID- 20584206 TI - Mechanisms of hypokalemia-induced ventricular arrhythmogenicity. AB - Hypokalemia is a common biochemical finding in cardiac patients and may represent a side effect of diuretic therapy or result from endogenous activation of renin angiotensin system and high adrenergic tone. Hypokalemia is independent risk factor contributing to reduced survival of cardiac patients and increased incidence of arrhythmic death. Animal studies demonstrate that hypokalemia induced arrhythmogenicity is attributed to prolonged ventricular repolarization, slowed conduction, and abnormal pacemaker activity. The prolongation of ventricular repolarization in hypokalemic setting is caused by inhibition of outward potassium currents and often associated with increased propensity for early afterdepolarizations. Slowed conduction is attributed to membrane hyperpolarization and increased excitation threshold. Abnormal pacemaker activity is attributed to increased slope of diastolic depolarization in Purkinje fibers, as well as delayed afterdepolarizations caused by Ca2+ overload secondary to inhibition of Na+--K+ pump and stimulation of the reverse mode of the Na+--Ca2+ exchange. Hypokalemia effect on repolarization is not uniform at distinct ventricular sites thereby contributing to amplified spatial repolarization gradients which promote unidirectional conduction block. In hypokalemic heart preparations, the prolongation of action potential may be associated with shortening of effective refractory period, thus increasing the propensity for ventricular re-excitation over late phase of repolarization. Shortened refractoriness and slowed conduction contribute to reduced excitation wavelength thereby facilitating re-entry. The interplay of triggering factors (early and delayed afterdepolarizations, oscillatory prepotentials in Purkinje fibers) and a favorable electrophysiological substrate (unidirectional conduction block, reduced excitation wavelength, increased critical interval for ventricular re excitation) may account for the mechanism of life-threatening tachyarrhythmias in hypokalemic patients. PMID- 20584207 TI - Gender-specific aspects of treatment of cardiovascular risk factors in primary and secondary prevention. AB - In men, cardiovascular diseases (CVD) increase steadily by the age of 35 years and reach a plateau in the 7th decade of life, whereas in women few years after the menopause, from about 50 years, the incidence of cardio-cerebro-vascular diseases progressively increases, becoming the leading cause of mortality and morbidity. Because of the greater incidence of CVD in men until the early 1980s, the information on cardiovascular risk factors has been gathered mainly from men and then translated in women. But sex steroid milieu has a different impact on cardiovascular risk profile, as cardiovascular risk factors have a different importance in determining future cardiovascular events in the two sexes and therapeutic strategies have a different impact on reducing cardiovascular risk in the two sexes. Aim of this study is to review the gender-specific aspects influencing the development of cardiovascular risk factors and cardiovascular preventative strategies both in primary and in secondary prevention. PMID- 20584208 TI - Effects induced by inhibitors of the phosphatidylinositol 3-kinase/Akt and nitric oxide synthase/guanylyl cyclase pathways on the isometric contraction in rat aorta: a comparative study. AB - This work was aimed to determine whether isometric contraction in Wistar rat aorta is related to the phosphatidylinositol 3-kinase (PI3K)/Akt-dependent activation of endothelial nitric oxide synthase (eNOS). Basically, we hypothesized that additional increases in active tone occur after the pharmacological inhibition of a transduction pathway involved in NO synthesis or action. In intact aortic rings contracted with phenylephrine or high K(+), the cumulative administration of the PI3K inhibitor, LY294002, elicited significant decreases--but not supplementary increases--in tone. In endothelium-intact tissues, on the other hand, the Akt1/2 kinase inhibitor did not alter phenylephrine- and K(+)-induced isometric contractions. The PI3K inhibitor wortmannin (1 * 10(-7) m) produced a significant supplementary contraction only in endothelium-intact aortic rings precontracted with phenylephrine. Higher concentrations of this inhibitor produced relaxations of phenylephrine and high K(+)-constricted endothelium-intact and endothelium-denuded aortic rings. LY294002 and wortmannin did not cause any potentiating effect on phenylephrine- and angiotensin II-induced concentration-dependent contractile responses in endothelium-intact tissues. In intact aortic rings contracted with phenylephrine or high K(+), the addition of the NOS inhibitor, L-NAME, or the guanylyl cyclase inhibitor, ODQ, further augmented tone in a concentration-dependent manner, and these supplementary contractions were significantly reduced by endothelium removal. Taken together, our data suggest that the PI3K/Akt pathway is not counteracting aortic isometric contractions by activation of the eNOS. It appears, on the other hand, that the smooth muscle PI3K can stimulate contraction without activation of the protein kinase Akt in response to GPCR agonists and high K(+). PMID- 20584209 TI - Do all antihypertensive drugs improve carotid intima-media thickness? A network meta-analysis of randomized controlled trials. AB - The many clinical trials investigating the effect of various antihypertensive drugs on carotid intima-media thickness (CIMT) produced conflicting results. We used meta-analysis to evaluate CIMT changes and network meta-analysis to rank drugs according to the magnitude of these changes. We identified 31 randomized controlled trials listed in three databases as of January 2008. Using a random effects model, we found a significant CIMT decrease with antihypertensive drugs compared to placebo (-0.10 [-0.16; -0.04]). Overall effect sizes vs. placebo were significant for angiotensin-converting enzyme (ACE) inhibitors (-0.08 [-0.14; 0.02]), and a trend was found for beta-blockers (-0.09 [-0.19; 0.01]). The data did not allow other direct comparisons vs. placebo. Significant benefits were found for calcium-channel blockers (CCBs) compared to both ACE inhibitors (0.37 [0.20; 0.54]), as well as for angiotensin II receptor blockers (ARBs) compared to beta-blockers (0.42 [0.29; 0.55]). Diuretics were less efficient than CCBs (-0.09 [-0.16; -0.02]). Indirect comparisons with network meta-analysis showed significant effects of CCBs and ARBs vs. placebo (both P < 0.05) and vs. diuretics (both P < 0.001). The CIMT decrease with ACE inhibitors and beta blockers was greater than with diuretics (both P < 0.05) but was not different from the placebo effect. In subgroup analyses, significant benefits occurred with lower baseline CIMT values and shorter treatment durations but were unrelated to the size of the blood pressure decrease. In conclusion, among antihypertensive drugs, CCBs and ARBs have the greatest effect on CIMT. PMID- 20584210 TI - N-acetylcysteine-induced headache in hospitalized patients with acute acetaminophen overdose. AB - Intravenous N-acetylcysteine (IV-NAC) is usually regarded as a safe antidote to acetaminophen overdose. However, during infusion of the loading dose, adverse drug reactions such as a headache may occur. The objectives of this study were to investigate the prevalence of headache in patients presenting to hospital after acetaminophen overdose and to determine which clinical findings are most predictive of headache among these patients. This is a retrospective cohort study of hospital admissions for acute acetaminophen overdose that was conducted over a period of 4 years from January 1, 2005 to December 31, 2008. Demographic data, clinical characteristics, and predictors of headache were analyzed. spss 15 was used for data analysis. Two-hundred and fifty-five patients were studied; their mean age was 23.1 +/- 1.6; 83.9% of them were women and 14.9% had a headache during hospitalization. Headache among patients was significantly associated with IV-NAC administration (P = 0.001), intentional ingestion of drug (P = 0.04), acetaminophen concentration above 'possible toxicity' treatment line (P = 0.04), a high acetaminophen concentration (P = 0.04), and a long hospital stay (P = 0.03). Multiple logistic regression showed a significant risk factor for headache in patients administered IV-NAC (P = 0.04). We recorded a high frequency of headache in patients with acute acetaminophen overdose in our geographical area. This study suggests that among those patients, the use of IV-NAC is associated with an increased risk of headache. PMID- 20584211 TI - Correlation of seizures and biochemical parameters of oxidative stress in experimentally induced inflammatory rat models. AB - The role of oxidative stress in the pathogenesis of various conditions including epilepsy, inflammatory bowel disease and rheumatoid arthritis is evolving. The aim of this study was to find out the correlation between various inflammatory models with seizures and antioxidant parameters. Fifty-four male rats were divided into three groups of colitis, adjuvant arthritis and cotton wool granuloma (CWG). Each group had three subgroups of control, model and treatment. Thalidomide was used as treatment in colitis and arthritis group, whereas etoricoxib was used in CWG group. In colitis and arthritis groups, thalidomide was administered for 3 and 17 days, respectively, whereas etoricoxib was administered for 7 days in CWG group. At the end of treatment protocols, a subconvulsive dose of pentylenetetrazole (PTZ) (40 mg/kg i.p.) was injected intraperitoneally to note seizure onset and score. After confirming the presence of inflammation by morphological and histological studies, plasma and brain biochemical parameters of oxidative stress were estimated. The models of colitis, arthritis and CWG were effectively produced as evidenced by morphological scores (P < 0.001). Thalidomide reduced the morphological score (P < 0.002) and seizure grade (P < 0.001), whereas increased seizure onset (P < 0.001) in the arthritis group. There was an increase in malondialdehyde levels in the brain of thalidomide-treated groups (P < 0.002) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. There was neither improvement in seizure nor any significant changes in lipid peroxidation and antioxidant enzyme levels in etoricoxib-treated group. Thalidomide was effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. As it increased lipid peroxidation and reduced SOD and GPx, further evaluation is necessary with respect to oxidative stress. PMID- 20584213 TI - Problem solved: erectile dysfunction (ED) = early death (ED). PMID- 20584214 TI - Peripheral artery disease: appreciating the asymptomatic - yet lethal - epidemic. PMID- 20584212 TI - Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans. AB - Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect the risk of nicotine dependence in a new sample of African Americans (AAs) (N = 710). We also analyzed this AA sample together with a European American (EA) sample (N = 2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7 and CHRNA10 show modest association with nicotine dependence risk in the AA sample. In addition, CHRNA4, CHRNB3-CHRNA6 and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor single nucleotide polymorphisms (SNPs) that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the AA sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in EAs and also 1.9% in AAs; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations. PMID- 20584215 TI - Novel oral anticoagulants: the potential relegation of vitamin K antagonists in clinical practice. PMID- 20584216 TI - Medical reasoning and the failure of electronic medical record systems in the United States. PMID- 20584217 TI - Adherence to statin therapy: the key to survival? PMID- 20584218 TI - Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus. AB - * A significant proportion of men with erectile dysfunction (ED) exhibit early signs of coronary artery disease (CAD), and this group may develop more severe CAD than men without ED (Level 1, Grade A). * The time interval among the onset of ED symptoms and the occurrence of CAD symptoms and cardiovascular events is estimated at 2-3 years and 3-5 years respectively; this interval allows for risk factor reduction (Level 2, Grade B). * ED is associated with increased all-cause mortality primarily due to increased cardiovascular mortality (Level 1, Grade A). * All men with ED should undergo a thorough medical assessment, including testosterone, fasting lipids, fasting glucose and blood pressure measurement. Following assessment, patients should be stratified according to the risk of future cardiovascular events. Those at high risk of cardiovascular disease should be evaluated by stress testing with selective use of computed tomography (CT) or coronary angiography (Level 1, Grade A). * Improvement in cardiovascular risk factors such as weight loss and increased physical activity has been reported to improve erectile function (Level 1, Grade A). * In men with ED, hypertension, diabetes and hyperlipidaemia should be treated aggressively, bearing in mind the potential side effects (Level 1, Grade A). * Management of ED is secondary to stabilising cardiovascular function, and controlling cardiovascular symptoms and exercise tolerance should be established prior to initiation of ED therapy (Level 1, Grade A). * Clinical evidence supports the use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy in men with CAD and comorbid ED and those with diabetes and ED (Level 1, Grade A). * Total testosterone and selectively free testosterone levels should be measured in all men with ED in accordance with contemporary guidelines and particularly in those who fail to respond to PDE5 inhibitors or have a chronic illness associated with low testosterone (Level 1, Grade A). * Testosterone replacement therapy may lead to symptomatic improvement (improved wellbeing) and enhance the effectiveness of PDE5 inhibitors (Level 1, Grade A). * Review of cardiovascular status and response to ED therapy should be performed at regular intervals (Level 1, Grade A). PMID- 20584219 TI - How to manage medications in the setting of liver disease with the application of six questions. AB - OBJECTIVE: Reviewing the current literature to guide clinicians managing medications in the setting of liver disease. LITERATURE SOURCES: Using the terms liver disease, medication management, and therapeutic monitoring, a literature review was conducted to identify peer-reviewed articles in MEDLINE (1966-April 2009). Reference citations were reviewed as an additional resource. Published English-language literatures, articles and trials were reviewed. Emphasis was placed on prospective, randomised, double-blind, placebo-controlled clinical trials. QUESTION SYNTHESIS: An informed decision on how to manage medications in the setting of liver disease should account for changes that transpire in a medication's first-pass metabolism, protein binding, volume of distribution, clearance and pharmacodynamic interactions. To incorporate these issues within one's thought process, clinicians can utilise the following six questions to evaluate a medication use: (i) Is the patient experiencing acute or chronic liver failure? (ii) Does the drug have high hepatic first-pass metabolism? (iii) Is the medication highly protein-bound? (iv) Is there a change in the volume of distribution for the medication? (v) Is the clearance of the medication significantly altered? and (vi) Is there a pharmacodynamic interaction with the medication? CONCLUSIONS: The introduction and use of six clinically relevant questions in the setting of liver disease can serve as a guide to clinicians who manage patients with liver disease. PMID- 20584220 TI - Management of patients with peripheral arterial disease in primary care: a cross sectional study in Germany. AB - BACKGROUND: Studies in the primary care setting are of high interest for assessing the management situation of patients with manifestations of atherothrombosis. AIMS: Therefore, we documented diagnostic procedures, characteristics, and management of patients with symptomatic and asymptomatic peripheral arterial disease (PAD). MATERIALS & METHODS: Prospective cross sectional study in primary care practices throughout Germany. RESULTS: A total of 671 patients with newly diagnosed PAD were included (mean age 69.1 years; 62.1% men). Cardiovascular risk factors were highly prevalent in the total PAD group: arterial hypertension in 84.2%, hyperlipidaemia in 75.5%, present smoking in 45.0% and diabetes mellitus in 47.3%. Atherothrombotic comorbidities were also frequent: coronary artery disease in 44.9% and cerebrovascular disease in 28.1%. For confirmation of diagnosis, patients were referred to specialists in 66.9% of cases. Overall, ankle brachial index was measured in 89.0%, and a clinical PAD score assessed in 66.6% (agreement of both measures with Cohen's kappa only, kappa = 0.039; p = 0.209). Drug treatment of risk factors (as secondary prophylaxis) in line with current guidelines was reported in a high percentage of patients: 88.6% with any antiplatelet drug, 69.3% with statins, 62.4% with angiotensin converting enzyme inhibitors, 23.5% with AT(1) receptor blockers and 43.9% with beta-blockers. Between asymptomatic and symptomatic PAD, differences in the risk factor/comorbidity profiles were small; however, the latter group received intensified treatment. CONCLUSION: Our findings confirm that patients with PAD pose a substantial challenge to physicians because of their high number of comorbidities. Compared with previous studies, management of such patients appears to have improved. PMID- 20584221 TI - Stability and antimicrobial effectiveness of treprostinil sodium in Sterile Diluent for Flolan. AB - INTRODUCTION: Long-term intravenous infusion of epoprostenol and treprostinil for treatment of pulmonary arterial hypertension (PAH) via a central venous catheter is associated with the risk of bloodstream infection (BSI). While several potential explanations exist for possible differences in BSI incidence among intravenous prostanoids, one hypothesis suggests that the alkaline pH of epoprostenol in Sterile Diluent for Flolan (SDF) has greater antimicrobial activity compared with the neutral pH of other common diluents such as sterile saline or water, which have been used for treprostinil. METHODS: The chemical stability and antimicrobial activity of 4 microg/ml and 130 microg/ml treprostinil in SDF were assessed according to United States and European Pharmacopeia. RESULTS: At both concentrations, treprostinil in SDF remained stable after incubation at 40 degrees C and ambient relative humidity for up to 52 h. Solution pH also remained stable (range 10.4-10.6), and the solutions were essentially free of particulate at all time points examined. Antimicrobial activity was measured using an antimicrobial effectiveness test after inoculation with five species of bacteria, yeast and mould. The antimicrobial activity of both concentrations of treprostinil met United States Pharmacopeia requirements. Further, the antimicrobial activity of treprostinil in SDF against gram-negative bacteria (> 4 log(10) reductions) exceeded that previously described for treprostinil in sterile saline. CONCLUSION: These results suggest that dilution of treprostinil with the alkaline solution SDF may reduce the risk of infection from inadvertent patient contamination compared with dilution of treprostinil in sterile saline. PMID- 20584222 TI - Evaluation of NT-proBNP to predict outcomes in advanced heart failure. AB - AIMS: To determine which factors predict outcomes in a group of patients with advanced heart failure, and in particular if NT-proBNP provides additional clinical and prognostic information to other haemodynamic and biochemical data. METHODS AND RESULTS: Ninety-one patients were studied who were being evaluated for heart transplantation, with 166 assessments. The patients had advanced heart failure as determined by median cardiac index of 2.0 l/min/m(2), left ventricular end-diastolic diameter of 7.0 mm and levels of NT-proBNP of 2473 pg/ml. Median follow-up time was 359 days. Clinicians were blinded to NT-proBNP levels. NT proBNP significantly correlated with cardiac index (R = -0.44, p < 0.001), right atrial pressure (R = 0.40, p < 0.001), pulmonary arterial wedge pressure (R = 0.38, p < 0.001) and albumin (R = -0.52, p < 0.001), and total bilirubin with right atrial pressure (R = 0.59, p < 0.001). Cardiac index was the most important independent predictor of outcome (p = 0.0001), although bilirubin (p = 0.001) and NT-proBNP (p < 0.05) were also significant. In patients with a 50% increase in NT proBNP, 64% had adverse outcomes, whereas those in whom levels were stable, 22% had adverse outcomes (p < 0.05). CONCLUSION: Cardiac index is the primary independent predictor of outcome in advanced heart failure when haemodynamic deterioration is evident. In situations where invasive haemodynamics are not available, total bilirubin (reflecting hepatic congestion) and NT-proBNP (related to haemodynamics) also provide important prognostic information. PMID- 20584223 TI - The association between serum uric acid level and coronary artery disease. AB - OBJECTIVE: This study was designed to determine the relationship between serum uric acid level and the presence and severity of coronary artery disease (CAD). METHODS: A total of 1012 patients who underwent coronary angiography were included in this study. All patients were assessed for the presence of cardiovascular risk factors and ongoing medications. Serum uric acid and creatinine level, as well as a fasting lipid profile and fasting blood glucose, were measured in all patients before the procedure. The severity of CAD was assessed by the Gensini score. RESULTS: Of 1012 patients (mean age, 59.4 +/- 10.24 years), 680 were men (mean age, 58.7 +/- 10.5 years) and 332 were women (mean age, 61.0 +/- 9.51 years). Of the study patients, 703 (69%) were hypertensive, 292 (28.9%) were diabetic (DM), 304 (30%) had a smoking history, 306 (30%) had low high-density lipoprotein cholesterol levels and 350 (34%) had hypertriglyceridaemia. CAD was present in 689 (68%) patients who were assessed by coronary angiography. One-, two- and three-vessel disease was detected in 32.6%, 32.5% and 34.9% of the patients respectively; left main coronary artery lesion was detected in 15% of the patients. A statistically significant difference in the mean uric acid concentrations was found between the patients with or without CAD [380 +/- 121 micromol/l (6.39 +/- 2.04 mg/dl) vs. 323.5 +/- 83.2 micromol/l (5.44 +/- 1.40 mg/dl) p < 0.001]. Based on logistic regression analysis, the increased serum uric acid level was found to be associated with the presence of CAD in both men and women (p < 0.001). The increased serum uric acid level was also found to be associated with the severity of CAD in both men and women based on multivariate linear regression analysis (p < 0.001). CONCLUSION: In conclusion, serum uric acid level was found to be associated with the presence and severity of CAD. PMID- 20584224 TI - The effect of healthcare provider education on diabetes management of hospitalised patients. AB - BACKGROUND: The importance of optimising blood glucose (BG) control in hospitalised patients is widely accepted. To determine whether focused education of physicians and nurses would result in measurable changes in glycaemic control, the effect of a diabetes-focused educational programme on point of care (POC) BG measures was monitored. METHODS: This programme included 2 h symposium and 2 h interactive session. The POC BG measures were determined at 2-month period prior to implementing the programme and the ensuing 7 months after. Outcome parameters included the mean BG values, the incidence of hyperglycaemia (BG > 180 mg/dl) and hypoglycaemia (BG < 60 mg/dl). The outcome parameters were analysed by comparing the Internal Medicine (target service) to other such as Neurology and Surgical Trauma where no programme was offered. RESULTS: On Internal Medicine, the mean BG decreased soon after implementing the programme and stayed lower than the baseline values over 7 months. The changes were significant at the third, fourth, seventh and the ninth month of the study. Hyperglycaemia decreased significantly (p < 0.05) on the third, fourth, seventh and eighth month, while hypoglycaemia increased following the education programmes. On Neurology and Surgical Trauma, the mean BG values were significantly higher, and hypoglycaemia was significantly lower during the same time frame. CONCLUSIONS: Implementing an educational programme for healthcare providers had significant effects on the lowering of mean BG values and the incidence of hyperglycaemia, but increased the risk of hypoglycaemia. The merits of such programmes need to be tested before their widespread implementation. PMID- 20584225 TI - Services for erectile dysfunction in the UK - a 12-month review of referrals to a west Midlands NHS clinic. AB - INTRODUCTION: Few studies have addressed the health economics of the provision of services for sexual dysfunction within the National Health Service. AIM: To evaluate the referral patterns, workload and prescribing costs in secondary care resulting from government guidance on erectile dysfunction (ED). METHOD: A review of 324 consecutive referral letters to the Good Hope Hospital Erectile Dysfunction Clinic was conducted to assess the purpose of referral. Prescribing data and costs were assessed over the same 2-year period. RESULTS: Severe distress was the main reason for referral in 54% of referrals. Long term prescribing according to government guidance doubled the cost of care and created an unsustainable increase in clinic and pharmacy workload. CONCLUSIONS: Existing regulations designed to control costs of ED therapy have created health inequalities, waste of resources and have increased the overall cost of care. PMID- 20584226 TI - Documentation of cerebrospinal fluid opening pressure and other important aspects of lumbar puncture in acute headache. AB - BACKGROUND: Measuring cerebrospinal fluid (CSF) opening pressure by lumbar puncture (LP) is an essential tool in the investigation of patients with acute headache. AIM: To assess documentation of opening CSF pressure in those with acute headache undergoing LP. General documentation of the procedure and CSF investigations was also assessed. METHODS: Retrospective review of medical records of patients admitted to a teaching hospital Acute Medical Admissions Unit over a three-month period with a presenting complaint of headache. RESULTS: A total of 106 patients presented with headache of whom 48 patients had at least one LP attempted. Only 41 patients (85%, 95% CI 72-94) had their LP documented. Of 47 patients that had a successful LP, 22 (47%) had a recorded opening pressure. Eighteen (32%) of all patients had their position recorded, with seven (15%) patients having had position and opening pressure documented. Twenty patients (43%) had the appropriate results documented. Twelve patients (31%) had paired serum glucose measured. CONCLUSIONS: Documentation of a LP for headache in the acute setting was generally poor. CSF opening pressure measurement was frequently omitted and no appropriate action taken if high. Paired serum glucose was rarely measured. Acute physicians may benefit from a proposed protocol and documentation sticker. PMID- 20584228 TI - Systematic review and meta analysis: polyethylene glycol in adults with non organic constipation. AB - It is unclear how polyethylene glycol (PEG) laxatives compare with other classes of laxative in terms of efficacy. To assess efficacy of PEG vs. placebo and active comparators in adults with non-organic constipation. Text Word searches were carried out on MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Clinical Trials and Google Scholar databases covering the period January 1970 to October 2009. Search terms were (constipation) AND (randomised OR randomized) AND (PEG OR polyethylene OR macrogol OR movicol OR idrolax OR miralax OR transipeg OR forlax OR colyte OR golytely OR isocolan OR nulytely) NOT colonoscopy. Only published randomised controlled trials, with a parallel-group or cross-over design, comparing oral PEG with placebo or a comparator laxative in adults with a history of non-organic constipation, were included. The frequency of defaecation in each arm, on completion of the protocol-defined treatment duration was extracted. All pooled analyses were based on random effect models. Of the 20 qualifying studies, 10 were vs. placebo, seven were vs. lactulose, and four were vs. other agents. One study compared PEG, placebo and lactulose. PEG treatment resulted in a highly significant increase in defaecations/week over placebo (all studies: additional 1.98 stools/week; p = 0.0003, high-quality studies: additional 2.34 stools/week; p = 0.0001) and over lactulose (all studies: additional 1 stool/week; p = 0.0017, high-quality studies: additional 1.65 stools/week; p = 0.021). This meta analysis is the only quantitative statistical analysis to have been published in the field. PEG was found to be a more effective laxative than lactulose in adult patients with constipation. PMID- 20584227 TI - Efficacy of almotriptan in early intervention for treatment of acute migraine in a primary care setting: the START study. AB - AIMS: The benefits of taking almotriptan early for acute migraine when pain is mild have clearly been demonstrated in the neurology setting. The aim of this study was to determine whether similar benefits with early intervention of almotriptan can be achieved in everyday general practice, where most migraineurs are managed. METHODS: In this European, prospective, observational study, patients were asked to treat up to three migraine attacks over a 2-month period with almotriptan 12.5 mg administered within 1 h of pain onset and when pain was mild (early + mild intervention group). RESULTS: A total of 501 patients were enrolled in primary care centres across Spain, France and Italy. The intention-to treat analysis involved 454 patients who reported 1174 migraine attacks, with early intervention being used in 138 of these attacks. A greater proportion of patients who took almotriptan early + mild for their first migraine attack (n = 42) were pain free at 2 h compared with those in the non-early + mild intervention group (n = 410) (62% vs. 35%; p < 0.001). Similar results were obtained for all migraine attacks comparison [65% (n = 138) vs. 38% (n = 1036); p < 0.001]. Other secondary end-points were also significantly in favour of early + mild treatment, including sustained pain free (SPF), SPF with no adverse events (SNAE), and time lost because of migraine (all p < 0.001). Almotriptan was well tolerated with no serious adverse events reported. CONCLUSIONS: In the primary care setting, early intervention with almotriptan for treatment of migraine provides significant clinical benefits compared with delaying treatment and/or waiting until pain intensity has progressed beyond mild. PMID- 20584229 TI - Drug and dietary interactions of the new and emerging oral anticoagulants. AB - Oral warfarin is associated with extensive food and drug interactions, and there is a need to consider such interactions with the new oral anticoagulants (OACs) dabigatran etexilate, rivaroxaban and apixaban. A literature survey was conducted using PubMed, EMBASE and recent abstracts from thrombosis meetings to identify publications related to food, drug and dietary supplement interaction studies with dabigatran etexilate, rivaroxaban and apixaban. Clinical experience regarding food interactions is currently limited. Regarding drug-drug interactions, dabigatran requires caution when used in combination with strong inhibitors or inducers of P-glycoprotein, such as amiodarone or rifampicin. Rivaroxaban (and possibly apixaban) is contraindicated in combination with drugs that strongly inhibit both cytochrome P450 3A4 and P-glycoprotein, such as azole antimycotics, and caution is required when used in combination with strong inhibitors of only one of these pathways. Important drug interactions of the new OACs that can lead to adverse clinical reactions may also occur with non steroidal anti-inflammatory drugs and antiplatelet drugs, such as aspirin and clopidogrel. Over-the-counter (OTC) medications and food supplements (e.g. St. John's Wort) may also interact with the new OACs. Given the common long-term use of drugs for some chronic disorders, the frequent use of OTC medications and the need for multiple treatments in special populations, such as the elderly people, it is essential that the issue of drug interactions is properly evaluated. New OACs offer significant potential advantages to the field of venous thromboprophylaxis, but we should not fail to appreciate their lack of extensive clinical experience. PMID- 20584230 TI - Pharmacological and non-pharmacological treatment of non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis and steatohepatitis to cirrhosis. Based on its strongest risk factors namely visceral obesity and insulin resistance, NAFLD is thought to be the hepatic manifestation of the metabolic syndrome and is considered to be the most common liver disorder in Western countries. Pathophysiological mechanisms include an enlarged pool of fatty acids, subclinical inflammation, oxidative stress and imbalances of various adipocytokines such as adiponectin. Accordingly, targets for therapeutic interventions are miscellaneous: amelioration of obesity by pharmacological, surgical or lifestyle intervention has been evaluated with success in numerous, but not all studies. Some efficacy was reported for metformin and short-term glitazone treatment. In a large recently reported trial, vitamin E supplementation improved biochemical and histological markers in subjects with non-alcoholic steatohepatitis. Blockade of the endocannabinoid system has been proposed to be a promising target in NAFLD; however, very recently the cannabinoid receptor blocker rimonabant has been withdrawn because of central nervous system toxicity. Cytoprotective therapies and statins have been mainly ineffective in NAFLD. New but so far insufficiently studied therapeutic approaches include inhibitors of the renin-angiotensin system as well as incretin mimetics respectively. PMID- 20584231 TI - Thyroid hormone replacement: an iatrogenic problem. AB - Thyroid hormone replacement is one of the very few medical treatments devised in the 19th century that still survive. It is safe, very effective and hailed as a major success by patients and clinicians. Currently, it is arguably the most contentious issue in clinical endocrinology. The current controversy and patient disquiet began in the early 1970s, when on theoretical grounds and without proper assessment, the serum thyrotropin (TSH) concentration was adopted as the means of assessing the adequacy of thyroxine replacement. The published literature shows that the serum TSH concentration is a poor indicator of clinical status in patients on thyroxine. The adequacy of thyroxine replacement should be assessed clinically with the serum T3 being measured, when required, to detect over replacement. PMID- 20584232 TI - Irrespective of stomach conditions. PMID- 20584233 TI - Beneficial effects of long-term enzyme replacement therapy in a child with Fabry disease. PMID- 20584234 TI - Celebrating a career in neuroendocrinology. PMID- 20584235 TI - Rates of depression and participation in senior centre activities in community dwelling older persons. AB - The purpose of this study was to determine the role that senior citizen centres play in decreasing depression in community-dwelling older persons. A quantitative cross-sectional design was utilized. A questionnaire was used to determine demographic and lifestyle data. The dependent variable, depression symptoms, was measured using the 15-point Geriatric Depression Scale. Eighty-eight per cent stated that they attend for the friends and social support. Second, the study demonstrated that community-dwelling older persons can have those needs fulfilled at the senior centres. Ninety-four per cent of them have made close friends at their centres. Ninety-four per cent stated that their lives had improved since attending the senior centre. Eighty-six per cent felt they had made friends on whom they could rely when needed. PMID- 20584236 TI - The Strengthening Families Program 10-14: influence on parent and youth problem solving skill. AB - The aim of this paper is to report the results of a preliminary examination of the efficacy of the Strengthening Families Program (SFP) 10-14 in improving parent and youth problem-solving skill. The Hypotheses in this paper include: (1) youth and parents who participated in SFP would have lower mean scores immediately (T2) and 6 months (T3) post intervention on indicators of hostile and negative problem-solving strategies; (2) higher mean scores on positive problem solving strategies; and (3) youth who participated in SFP would have higher mean scores at T2 and at T3 on indicators of individual problem solving and problem solving efficacy than youth in the comparison group. The dyads were recruited from elementary schools that had been stratified for race and assigned randomly to intervention or comparison conditions. Mean age of youth was 11 years (SD = 1.04). Fifty-seven dyads (34-intervention&23-control) were videotaped discussing a frequently occurring problem. The videotapes were analysed using the Iowa Family Interaction Rating Scale (IFIRS) and data were analysed using Dyadic Assessment Intervention Model. Most mean scores on the IFIRS did not change. One score changed as predicted: youth hostility decreased at T3. Two scores changed contrary to prediction: parent hostility increased T3 and parent positive problem solving decreased at T2. SFP demonstrated questionable efficacy for problem solving skill in this study. PMID- 20584237 TI - Could repressive coping be a mediating factor in the symptom profile of individuals diagnosed with schizophrenia? AB - Despite a relatively high prevalence, and the enduring patronage of the disorder by psychiatry and the pharmaceutical industry, innovative conceptualization of schizophrenia in a client-empowering and quality of life-enhancing way appears to represent a vacuum within the clinical agenda, certainly taking second place to 'patient management'. However, against this bland background of medicalization of what is clearly a poorly understood and complex multifactorial syndrome, innovative treatment approaches aimed at symptom control, in particular, the stress vulnerability model (SVM), have been developed. However, the SVM is an incomplete model of patient experience and says little of aetiological note. One area of psychological function that may give further insight into the symptom experience associated with schizophrenia within the context of stress vulnerability concerns the mechanisms of repression. Ironically, the notion of repression will for many represent the epitome of nonevidence-based psychiatric theory and related psychodynamic therapy practice. However, more contemporary work within the psychological literature has aimed to make the concept both measurable and observable. No longer occluded by the context of psychoanalysis, cognitive science accounts of repression may be of value in facilitating understanding of the variability and predictability of symptoms of schizophrenia and may provide a dimension of therapeutic engagement allied to the SVM. PMID- 20584238 TI - Expectations and illusions: a position paper on the relationship between mental health practitioners and social exclusion. AB - Over the last 10 years, the social inclusion agenda has been gaining momentum as a policy driver in mental health services. Prior to the seminal Social Exclusion Unit (SEU) report, Mental Health and Social Exclusion, there was a lack of awareness concerning the pervasive links between social exclusion and mental health problems. In the report, the SEU suggested that mental health practitioners themselves may actually be contributing to this social exclusion. This finding has been given limited coverage in both social inclusion literature and research. The current paper is a positioned commentary further exploring the relationship between practitioners and the social exclusion of mental health service users. A literature review was conducted in order to identify themes among factors which appear to moderate and contribute to this relationship. These factors are presented and implications for inclusive practice are explored. PMID- 20584239 TI - Family members' involvement in psychiatric care: experiences of the healthcare professionals' approach and feeling of alienation. AB - The involvement of family members in psychiatric care is important for the recovery of persons with psychotic disorders and subsequently reduces the burden on the family. Earlier qualitative studies suggest that the participation of family members can be limited by how they experience the professionals' approach, which suggests a connection to the concept of alienation. Thus, the aim of this study was in a national sample investigate family members' experiences of the psychiatric health care professionals' approach. Data were collected by the Family Involvement and Alienation Questionnaire. The median level and quartiles were used to describe the distributions and data were analysed with non parametric statistical methods. Seventy family members of persons receiving psychiatric care participated in the study. The results indicate that a majority of the participants respond that they have experiencing a negative approach from the professionals, indicating lack of confirmation and cooperation. The results also indicate that a majority of the participants felt powerlessness and social isolation in the care being provided, indicating feelings of alienation. A significant but weak association was found between the family members' experiences of the professionals' approach and their feelings of alienation. PMID- 20584240 TI - Adolescents' strengths and difficulties: approach to attachment styles. AB - This research is a descriptive field study conducted in order to investigate the relationship between adolescent difficulties and the attachment style. The study aims to investigate the relationship between adolescent attachment style and strength and difficulties in Turkey. Children attachment style and difficulties pattern in the group of adolescents aged 11-16 years old were compared with each other. Several different questionnaires, including The Strength and Difficulties Questionnaire, The Relationship Scale Questionnaire were applied to 384 (mean age 12.10 +/- 1.4 years) adolescents. The data were analysed using descriptive statistics, Pearson correlation coefficients, anova, t-test, Kruskall Wallis and effect sizes. The adolescent secure attachment style was associated with increased levels of prosocial behaviour, decreased levels of emotional symptoms, hyperactivity/inattention, peer relationship problems, conduct problems, total difficulties scores. The adolescent fearful attachment style was associated with increased levels of emotional symptoms, and total difficulties scores. The adolescent dismissing attachment style was significantly associated with higher levels of emotional symptoms, hyperactivity/inattention, total difficulties scores and lower levels of prosocial behaviour. Adolescent strengths and difficulties are associated with their attachment style. Insecure attachment styles of dismissing and fearful were associated with increased mental symptom reporting. It is suggested that further studies may illuminate the clinical value of the attachment disorder and quantify parental contribution to psychopathology. Giving the therapeutic, structured mental support programme to adolescents that have attachment problems could be beneficial in improving mental status of these individuals. PMID- 20584241 TI - Relating realist metatheory to issues of gender and mental health. AB - This paper seeks to advance the debate that considers critical realism as an alternative approach for understanding gender and mental health and its relatedness to mental health research and practice. The knowledge base of how 'sex' and 'gender' affect mental health and illness is expanding. However, the way we conceptualize gender is significant and challenging as quite often our ability to think about 'gender' as independent of 'sex' is not common. The influences and interplay of how sex (biological) and gender (social) affect mental health and illness requires consideration. Critical realism suggests a shared ontology and epistemology for the natural and social sciences. While much of the debate surrounding gender is guided within a constructivist discourse, an exploration of the concept 'gender' is reflected on and some key realist propositions are considered for mental health research and practice. This is achieved through the works of some key realist theorists. Critical realism offers potential for research and practice in relation to gender and mental health because it facilitates changes in our understanding, while simultaneously, not discarding that which is already known. In so doing, it allows the biological (sex) and social (gender) domains of knowledge for mental health and illness to coexist, without either being reduced to or defined by the other. Arguably, greater depth and explanations for gender and mental health issues are presented within a realist metatheory. PMID- 20584242 TI - Health professionals' attitudes to depot injection antipsychotic medication: a systematic review. AB - Healthcare professionals are key providers of information about antipsychotic medication and may have a significant influence on the decisions that service users make about how their medication is delivered. This systematic review aimed to explore health professionals' attitudes and beliefs towards antipsychotic depot medication. A systematic search of AMED, BNI, CINAHL, EMBASE, HEALTH BUSINESS ELITE, HMIC, MEDLINE and PsycINFO was carried out, as well as hand searches of journals and citation searches. Studies were selected if the terms 'attitudes/beliefs' and 'depot/injection' were included in the title or abstract, if health professionals were participants in the study and if original data were included. The search strategy produced 131 papers. Eight relevant studies were then selected for the review. They included six cross-sectional surveys and two qualitative studies. It was shown that the research carried out is still very sparse. Depots are seen as old fashioned, stigmatizing, causingside effects and being costly, and they are often not prescribed because of a presumed adherence to oral medication. More research needs to be carried out to further explore these issues, to look at the role of non-medical prescribers and explore the relationship between health professionals' attitudes and those of service users. PMID- 20584243 TI - Psychotropic PRN use among older people's inpatient mental health services. AB - Concerns have been expressed about the use of antipsychotics with older people, particularly in those who have dementia. Pro re nata (PRN) psychotropic medications including antipsychotics are commonly used to manage disturbed and distressed behaviour. This audit aimed to understand the use of PRN psychotropic medications in older people's inpatient mental health services and the quality of prescriptions and nursing documentation associated with this. A retrospective audit was undertaken on 154 patients on 11 wards in three Mental Health Trusts in the North West of England. A proforma adapted from previous research was used to collect data. Eighty-seven patients were prescribed combinations of 14 psychotropic drugs in 145 different prescriptions as PRN. Seventy-six doses of PRN were administered to 26 patients (range 1-17 doses). The most commonly administered drug was Lorazepam (n = 28, 36.8%). Drugs were most frequently administered during the night (n = 33, 43.4%). The majority of administrations of PRN were not documented (n = 45, 59.2%). PRN appeared to be used differently (smaller doses and less frequently) in this study compared to previous research of those aged under 65. Further work needs to examine the use of the use of PRN psychotropic medicines and the older person, and focus on developing alternative nonpharmacological interventions. PMID- 20584250 TI - Photodynamic therapy in dermatology: state-of-the-art. AB - Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications. PMID- 20584251 TI - The minimal melanogenesis dose/minimal erythema dose ratio declines with increasing skin pigmentation using solar simulator and narrowband ultraviolet B exposure. AB - PURPOSE: To investigate the relation between pre-exposure skin pigmentation and the minimal melanogenesis dose (MMD)/minimal erythema dose (MED) ratio after a single narrowband ultraviolet B (nUVB) and solar simulator (Solar) exposure. BACKGROUND: In fair-skinned individuals, it is well known that the UV dose to give pigmentation (MMD) after a single exposure to UVB is larger than the UV dose to elicit erythema (MED) (MEDor=50% repigmentation. The repigmentation (>or=50%) in face/neck and trunk were much higher than that in the extremities (P<0.05). (3) The repigmentation (>or=50%) in disease duration of 2 years were 100.0% and 46.2% (P<0.05). (4) The average cumulative doses in the face/neck, trunk and extremities were 7.92+/-5.26, 9.93+/-7.36 and 22.13+/-8.15 J/cm(2). The doses in the face/neck and trunk were much lower than those in the extremities. (P<0.05). Side effects were limited mainly to symptomatic erythema. CONCLUSION: The clinical data indicate that the treatment of vitiligo using a 308 nm excimer laser is safe and effective. However, lesion location and disease duration may be the key factors affecting the clinical outcome. PMID- 20584253 TI - Eye protection for ultraviolet B phototherapy and psoralen ultraviolet A patients. AB - BACKGROUND/PURPOSE: We tested eye protection used for phototherapy patients. The study also established current practice concerning eye protection in a sample of UK phototherapy units. METHODS: The ultraviolet (UV) transmission spectra of 30 'UV protective' contact lenses were measured at 5 nm intervals between 290 and 400 nm. Sunglasses, small UV goggles and UV visors were tested between 270 and 420 nm. We surveyed the use of eye protection during phototherapy in 78 UK phototherapy units. RESULTS: All samples of sunglasses, eye protection goggles, visors and sunglasses comfortably passed previously published arbitrary limits of acceptability. Most contact lenses showed some protection in the UVB, but most had little or no UVA protection. Of 78 UK phototherapy units 21 (33%) use tinted goggles during UV exposures, two (3%) use a visor only, 28 (43%) use both and nine (14%) use clear plastic (probably polycarbonate) goggles. CONCLUSIONS: UV transmission for sunglasses and contact lenses is lower compared with samples tested 10 years ago. All samples of glasses, goggles and visors tested provided adequate protection in the UV range according to published arbitrary limits of acceptability. Most contact lenses did not provide significant UV protection in the UVA range. PMID- 20584254 TI - Photopatch testing negative in systemic quinine phototoxicity. AB - Drug-induced phototoxicity can be caused by topical or systemic agents and is diagnosed on the basis of clinical history, examination and appropriate investigations. Photopatch testing is the investigation of choice for topical photocontact allergic dermatitis, but its use in drug-induced phototoxicity has not been validated. We retrospectively analyzed the results of photopatch testing to the drug quinine sulfate in three patients in whom a diagnosis of drug-induced phototoxicity to this agent had been made. None of the three patients had positive photopatch test reactions at any time point. This demonstrates that in our patients, photopatch testing to quinine sulfate was not a useful additional investigation for diagnosing drug-induced phototoxicity. PMID- 20584255 TI - Treatment of progressive macular hypomelanosis with narrow-band ultraviolet B phototherapy. AB - Treatment for progressive macular hypomelanosis (PMH) has been disappointing. Recently, Propionibacterium acnes had been postulated as the causative agent and narrow-band ultraviolet B (NBUVB) had been shown to stimulate melanogenesis and has antibacterial properties. The aim of this study was to evaluate the effectiveness of NBUVB in the treatment of PMH. A retrospective analysis of PMH cases diagnosed and treated with NBUVB treatment from 1 January 2007 to 30 April 2009 at the National Skin Centre (NSC) was conducted. The diagnosis of PMH was clinical. Treatment with NBUVB (311 nm) was given twice to thrice weekly. The initial treatment dose was determined as 70% of the patients' individual 311 nm UVB minimal erythema dose. The dose was increased by 10-20% if previous treatment had caused no or slight erythema. Percentage repigmentation from baseline was assessed at each follow-up. A total of six patients diagnosed with PMH were treated with NBUVB in NSC in the past 2 years. Three patients had good improvement and the remainder had moderate improvement. Recurrence did occur. No adverse events were documented. The success of NBUVB as a monotherapy provides a viable and relatively safe, albeit temporary relief, for these individuals. PMID- 20584256 TI - Unsuccessful treatment of recalcitrant cutaneous discoid lupus erythematosus with photodynamic therapy. AB - Discoid lupus erythematosus (DLE) can be a therapeutic challenge. Antimalarials and topic steroids are the first-line standard therapies, while systemic steroids, immunomodulators (as azathioprine, methotrexate, cyclosporine), retinoids (acitretin), thalidomide, auranofin and dapsone are used as second-line therapies. We report two patients with recalcitrant DLE who were treated with three and two sessions of 5-aminolevulinic photodynamic therapy without an improvement and with a bad tolerance to the therapy. PMID- 20584257 TI - Preferential induction of endothelin-1 in a human epidermal equivalent model by narrow-band ultraviolet B light sources. AB - Narrow-band ultraviolet B (NB-UVB; 310-315 nm) is commonly used to treat vitiligo, but the mechanisms underlying the therapeutic effect have not been understood completely. Here, we evaluated the effects of broadband UVB (BB-UVB), NB-UVB, 308 nm xenon chloride (XeCl) excimer laser, and 308 nm XeCl excimer light on the expression of endothelin-1 (ET-1) in a cultured human epidermal tissue model. Our results provide a theoretical basis for the effectiveness of UVB irradiation, including excimer light and excimer laser, in the treatment of vitiligo. PMID- 20584258 TI - Narrow-band ultraviolet B as a potential alternative treatment for resistant psychogenic excoriation: an open-label study. AB - Narrow-band ultraviolet therapy has been used successfully for the treatment of inflammatory skin disorders and generalized pruritus. We have prospectively evaluated seven consecutive patients with resistant psychogenic excoriation (PE) treated with narrow-band ultraviolet B (NB-UVB). Approximately 70% of all patients showed improvement in their condition. NB-UVB therapy was well tolerated, with no serious side effects. We may conclude that, when treating a patient with PE, NB-UVB in combination with other approaches may provide extra benefit in resistant cases. PMID- 20584259 TI - Variables in full-body ultraviolet B treatment of skin diseases. AB - Ultraviolet B (UVB) treatment is most often performed according to a fixed schedule, not necessarily considering important variables such as UV intensity, type of UVB source and skin pigmentation. These variables can rather easily be taken into consideration by the right choice of dosing unit. The advantage of going from dosing in time to Joule to standard erythema dose or to minimal erythema dose is considered. The size of most variables may be diminished considerably. Following these guidelines, it is possible to increase the efficacy of UVB phototherapy without increasing the risk of unintentional burning. PMID- 20584260 TI - Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. AB - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. METHODS: Randomized crossover single blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg(-1) min(-1), n = 8), GLP-1 (0.75 pmol kg(-1) min(-1), n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C peptide, peptide YY (PYY) and ghrelin. KEY RESULTS: Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg(-1) min(-1) decreased gastric half emptying time from 128.5 +/- 34.0 min in controls to 93.3 +/- 6.3 and 85.2 +/- 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg(-1) min(-1) decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon like peptide-1 0.75 pmol kg(-1) min(-1) increased half-emptying time from 76.6 +/ 7.6 min to 329.4 +/- 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05-0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). CONCLUSION & INFERENCES: The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes. PMID- 20584261 TI - Contrasting effects of ghrelin and des-acyl ghrelin on the lumbo-sacral defecation center and regulation of colorectal motility in rats. AB - BACKGROUND: We have previously demonstrated that a centrally penetrant ghrelin receptor agonist enhances colorectal motility, through activation of the lumbo sacral defecation center (L6-S1 region of the spinal cord) in rats. In the present study, we examined the effects of the native peptide and its non-acylated counterpart in eliciting this stimulatory effect on colorectal motility. METHODS: Rats were anesthetised with alpha-chloralose and ketamine, and colorectal intraluminal pressure and propelled intraluminal liquid volume were recorded in vivo. KEY RESULTS: Intrathecal application of acylated ghrelin to the L6-S1 region of the spinal cord, but not intravenous application, elicited groups of phasic increases in colorectal intraluminal pressure that were associated with increased fluid output through the anal cannula. The effect was dose-dependent. The colokinetic effects of ghrelin were prevented if the pelvic nerves were severed. Reverse transcription polymerase chain reaction revealed the expression of the ghrelin and ghrelin receptor genes in the lumbo-sacral spinal cord. In contrast to acylated ghrelin, des-acyl ghrelin failed to cause changes in colorectal motility. However, when des-acyl ghrelin and ghrelin were applied simultaneously at the L6-S1 region, the ghrelin-induced enhancement of colorectal motility was significantly attenuated. CONCLUSION & INFERENCES: It is concluded that acylation of the ghrelin peptide is essential to promote propulsive contractions of the colorectum and that des-acyl ghrelin opposes this effect. At most other sites of ghrelin action, des-acyl ghrelin either has no effect or it mimics ghrelin. This is the first evidence that non-acylated ghrelin opposes the action of the acylated peptide in the spinal cord. PMID- 20584262 TI - Accuracy in assessment of colonic transit time with particles: how many markers should be used? AB - BACKGROUND: Colonic transit time (CTT) is often measured with particle methods in clinical practice, but few studies have evaluated the role of particle amounts for the results obtained. METHODS: Colonic transit time was studied in 28 subjects taking radiopaque particles for six consecutive days followed by an abdominal radiograph on day 7. Four distinguishable marker types were ingested simultaneously in an amount of 5, 10, 15, and 20 daily, respectively, and CTT calculated for each type as the number of retained markers divided by the daily intake. Reference values were based on 50 markers daily. KEY RESULTS: Accuracy measured as median deviation of CTT from reference was for 20 markers day(-1) 0.08 days, for 15 markers day(-1) 0.10 days, for 10 markers day(-1) 0.12 days, and for 5 markers day(-1) 0.20 days. The CTT values obtained with 5 markers day( 1) deviated significantly more from the reference value than CTT values obtained with 10 markers day(-1) (P < 0.05) and with 15 and 20 markers day(-1) (P < 0.01). Colonic transit times obtained with 20, 15, or 10 markers day(-1) did not differ significantly (P > 0.1). CONCLUSIONS & INFERENCES: Colonic transit time can be assessed with reasonable accuracy after repeated ingestion of particles. For clinical use, a daily amount of 10 or 12 markers is proposed for reporting CTT in days or hours, respectively. Doses below 10 daily yield a steeply increasing deviation from reference values. PMID- 20584263 TI - Gastric emptying of hexose sugars: role of osmolality, molecular structure and the CCK1 receptor. AB - BACKGROUND: It is widely reported that hexose sugars slow gastric emptying (GE) via osmoreceptor stimulation but this remains uncertain. We evaluated the effects of a panel of hexoses of differing molecular structure, assessing the effects of osmolality, intra-individual reproducibility and the role of the CCK(1) receptor, in the regulation of GE by hexoses. METHODS: Thirty one healthy non-obese male and female subjects were studied in a series of protocols, using a (13) C-acetate breath test to evaluate GE of varying concentrations of glucose, galactose, fructose and tagatose, with water, NaCl and lactulose as controls. GE was further evaluated following the administration of a CCK(1) receptor antagonist. Three subjects underwent repeated studies to evaluate intra-individual reproducibility. KEY RESULTS: At 250 mOsmol, a hexose-specific effect was apparent: tagatose slowed GE more potently than water, glucose and fructose (P < 0.05). Fructose (P < 0.05) also slowed GE, but with substantial inter-, but not intra-, individual differences. As osmolality increased further the hexose-specific differences were lost. At 500 mOsmol, all hexoses slowed GE compared with water (P < 0.05), whereas lactulose and saline did not. The slowing of GE by hexose sugars appeared to be CCK(1) receptor-dependent. CONCLUSIONS & INFERENCES: The effects of hexose sugars on GE appear related to their molecular structure rather than osmolality per se, and are, at least in part, CCK(1) receptor-dependent. PMID- 20584264 TI - Psychometric properties of questionnaires evaluating health-related quality of life and functional status in polytrauma patients with lower extremity injury. AB - BACKGROUND: Long term disability is common among polytrauma patients. However, as yet little information exists on how to adequately measure functional status and health-related quality of life following polytrauma. AIMS: To establish the unidimensionality, internal consistency and validity of two health-related quality of life measures and one functional status questionnaire among polytrauma patients. METHODS: 186 Patients with severe polytrauma including lower extremity injury completed the Sickness Impact Profile-136 (SIP-136), the Medical Outcomes Study 36-Item Short Health Survey (SF-36) and the Groningen Activity Restriction Scale (GARS) 15 months after injury. Unidimensionality and internal consistency was assessed by principal components analysis and Cronbach's alpha (alpha). To test the construct validity of the questionnaires, predetermined hypotheses were tested. RESULTS: The unidimensionality and internal consistency of the GARS and the SF-36, but not the SIP-136 were supported. The construct validity of the SF 36, GARS and to a lesser extent the SIP-136 was confirmed. CONCLUSION: The SF-36 and the GARS appear to be preferable for use in polytrauma patients over the SIP 136. PMID- 20584266 TI - Mental health policy in Kenya -an integrated approach to scaling up equitable care for poor populations. AB - BACKGROUND: Although most donor and development agency attention is focussed on communicable diseases in Kenya, the importance of non-communicable diseases including mental health and mental illness is increasingly apparent, both in their own right and because of their influence on health, education and social goals. Mental illness is common but the specialist service is extremely sparse and primary care is struggling to cope with major health demands. Non health sectors e.g. education, prisons, police, community development, gender and children, regional administration and local government have significant concerns about mental health, but general health programmes have been surprisingly slow to appreciate the significance of mental health for physical health targets. Despite a people centred post colonial health delivery system, poverty and global social changes have seriously undermined equity. This project sought to meet these challenges, aiming to introduce sustainable mental health policy and implementation across the country, within the context of extremely scarce resources. METHODS: A multi-faceted and comprehensive programme which combined situation appraisal to inform planning, sustained intersectoral policy dialogue at national and regional level; establishment of a health sector system for coordination, supervision and training of at each level (national, regional, district and primary care); development workshops; production of toolkits, development of guidelines and standards; encouragement of intersectoral liaison at national, regional, district and local levels; public education; and integration of mental health into health management systems. RESULTS: The programme has achieved detailed situation appraisal, epidemiological needs assessment, inclusion of mental health into the health sector reform plans, and into the National Package of Essential Health Interventions, annual operational plans, mental health policy guidelines to accompany the general health policy, tobacco legislation, adaptation of the WHO primary care guidelines for Kenya, primary care training, construction of a quality system of roles and responsibilities, availability of medicines at primary care level, some strengthening of intersectoral liaison with police, prisons and schools, and public education about mental health. CONCLUSIONS: The project has demonstrated the importance of using a multi-faceted and comprehensive programme to promote sustainable system change, key elements of which include a focus on the use of rapid appropriate assessment and treatment at primary care level, strengthening the referral system, interministerial and intersectoral liaison, rehabilitation, social inclusion, promotion and advocacy to mobilize community engagement. PMID- 20584265 TI - Newer insights into the mechanism of action of Psidium guajava L. leaves in infectious diarrhoea. AB - BACKGROUND: Psidium guajava L., Myrtaceae, is used widely in traditional medicine for the treatment of diarrhoea, dysentery, gastroenteritis, stomachaches, and indigestion. However, the effect of the leaf extract of P. guajava on the pathogenesis of infectious diarrhoea has not been studied. The present study evaluates the effect of a hot aqueous extract (decoction) of dried leaves of P. guajava on parameters associated with pathogenicity of infectious diarrhoea. The aim was to understand its possible mechanism(s) of action in controlling infectious diarrhoea and compare it with quercetin, one of the most reported active constituents of P. guajava with antidiarrhoeal activity. METHODS: The crude decoction and quercetin were studied for their antibacterial activity and effect on virulence features of common diarrhoeal pathogens viz. colonization of epithelial cells and production and action of enterotoxins. Colonization as measured by adherence of enteropathogenic Escherichia coli (EPEC) and invasion of enteroinvasive E. coli (EIEC) and Shigella flexneri was assessed using HEp-2 cell line. The production of E. coli heat labile toxin (LT) and cholera toxin (CT) and their binding to ganglioside monosialic acid (GM1) were studied by GM1-ELISA whereas the production and action of E. coli heat stable toxin (ST) was assessed by suckling mouse assay. RESULTS: The decoction of P. guajava showed antibacterial activity towards S. flexneri and Vibrio cholerae. It decreased production of both LT and CT and their binding to GM1. However, it had no effect on production and action of ST. The decoction also inhibited the adherence of EPEC and invasion by both EIEC and S. flexneri to HEp-2 cells. Quercetin, on the other hand, had no antibacterial activity at the concentrations used nor did it affect any of the enterotoxins. Although it did not affect adherence of EPEC, it inhibited the invasion of both EIEC and S. flexneri to HEp-2 cells. CONCLUSION: Collectively, the results indicate that the decoction of P. guajava leaves is an effective antidiarrhoeal agent and that the entire spectrum of its antidiarrhoeal activity is not due to quercetin alone. PMID- 20584267 TI - Comparing the retention mechanisms of tandem duplicates and retrogenes in human and mouse genomes. AB - BACKGROUND: Multiple models have been proposed to interpret the retention of duplicated genes. In this study, we attempted to compare whether the duplicates arising from tandem duplications and retropositions are retained by the same mechanisms in human and mouse genomes. RESULTS: Both sequence and expression similarity analyses revealed that tandem duplicates tend to be more conserved, whereas retrogenes tend to be more divergent. The duplicability of tandem duplicates is also higher than that of retrogenes. However, positive selection seems to play significant roles in the retention of both types of duplicates. CONCLUSIONS: We propose that dosage effect is more prevalent in the retention of tandem duplicates, while 'escape from adaptive conflict' (EAC) effect is more prevalent in the retention of retrogenes. PMID- 20584268 TI - Patient safety in Dutch primary care: a study protocol. AB - BACKGROUND: Insight into the frequency and seriousness of potentially unsafe situations may be the first step towards improving patient safety. Most patient safety attention has been paid to patient safety in hospitals. However, in many countries, patients receive most of their healthcare in primary care settings. There is little concrete information about patient safety in primary care in the Netherlands. The overall aim of this study was to provide insight into the current patient safety issues in Dutch general practices, out-of-hours primary care centres, general dental practices, midwifery practices, and allied healthcare practices. The objectives of this study are: to determine the frequency, type, impact, and causes of incidents found in the records of primary care patients; to determine the type, impact, and causes of incidents reported by Dutch healthcare professionals; and to provide insight into patient safety management in primary care practices. DESIGN AND METHODS: The study consists of three parts: a retrospective patient record study of 1,000 records per practice type was conducted to determine the frequency, type, impact, and causes of incidents found in the records of primary care patients (objective one); a prospective component concerns an incident-reporting study in each of the participating practices, during two successive weeks, to determine the type, impact, and causes of incidents reported by Dutch healthcare professionals (objective two); to provide insight into patient safety management in Dutch primary care practices (objective three), we surveyed organizational and cultural items relating to patient safety. We analysed the incidents found in the retrospective patient record study and the prospective incident-reporting study by type of incident, causes (Eindhoven Classification Model), actual harm (severity-of-outcome domain of the International Taxonomy of Medical Errors in Primary Care), and probability of severe harm or death. DISCUSSION: To estimate the frequency of incidents was difficult. Much depended on the accuracy of the patient records and the professionals' consensus about which types of adverse events have to be recognized as incidents. PMID- 20584269 TI - Protein complex prediction via verifying and reconstructing the topology of domain-domain interactions. AB - BACKGROUND: High-throughput methods for detecting protein-protein interactions enable us to obtain large interaction networks, and also allow us to computationally identify the associations of proteins as protein complexes. Although there are methods to extract protein complexes as sets of proteins from interaction networks, the extracted complexes may include false positives because they do not account for the structural limitations of the proteins and thus do not check that the proteins in the extracted complex can simultaneously bind to each other. In addition, there have been few searches for deeper insights into the protein complexes, such as of the topology of the protein-protein interactions or into the domain-domain interactions that mediate the protein interactions. RESULTS: Here, we introduce a combinatorial approach for prediction of protein complexes focusing not only on determining member proteins in complexes but also on the DDI/PPI organization of the complexes. Our method analyzes complex candidates predicted by the existing methods. It searches for optimal combinations of domain-domain interactions in the candidates based on an assumption that the proteins in a candidate can form a true protein complex if each of the domains is used by a single protein interaction. This optimization problem was mathematically formulated and solved using binary integer linear programming. By using publicly available sets of yeast protein-protein interactions and domain-domain interactions, we succeeded in extracting protein complex candidates with an accuracy that is twice the average accuracy of the existing methods, MCL, MCODE, or clustering coefficient. Although the configuring parameters for each algorithm resulted in slightly improved precisions, our method always showed better precision for most values of the parameters. CONCLUSIONS: Our combinatorial approach can provide better accuracy for prediction of protein complexes and also enables to identify both direct PPIs and DDIs that mediate them in complexes. PMID- 20584270 TI - Detection of quantitative trait loci affecting haematological traits in swine via genome scanning. AB - BACKGROUND: Haematological traits, which consist of mainly three components: leukocyte traits, erythrocyte traits and platelet traits, play extremely important role in animal immune function and disease resistance. But knowledge of the genetic background controlling variability of these traits is very limited, especially in swine. RESULTS: In the present study, 18 haematological traits (7 leukocyte traits, 7 erythrocyte traits and 4 platelet traits) were measured in a pig resource population consisting of 368 purebred piglets of three breeds (Landrace, Large White and Songliao Black Pig), after inoculation with the swine fever vaccine when the pigs were 21 days old. A whole-genome scan of QTL for these traits was performed using 206 microsatellite markers covering all 18 autosomes and the X chromosome. Using variance component analysis based on a linear mixed model and the false discovery rate (FDR) test, 35 QTL with FDR < 0.10 were identified: 3 for the leukocyte traits, 28 for the erythrocyte traits, and 4 for the platelet traits. Of the 35 QTL, 25 were significant at FDR < 0.05 level, including 9 significant at FDR < 0.01 level. CONCLUSIONS: Very few QTL were previously identified for hematological traits of pigs and never in purebred populations. Most of the QTL detected here, in particular the QTL for the platelet traits, have not been reported before. Our results lay important foundation for identifying the causal genes underlying the hematological trait variations in pigs. PMID- 20584271 TI - Does chocolate reduce blood pressure? A meta-analysis. AB - BACKGROUND: Dark chocolate and flavanol-rich cocoa products have attracted interest as an alternative treatment option for hypertension, a known risk factor for cardiovascular disease. Previous meta-analyses concluded that cocoa-rich foods may reduce blood pressure. Recently, several additional trials have been conducted with conflicting results. Our study summarises current evidence on the effect of flavanol-rich cocoa products on blood pressure in hypertensive and normotensive individuals. METHODS: We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP) for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive). Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P < 0.05. RESULTS: Fifteen trial arms of 13 assessed studies met the inclusion criteria. Pooled meta analysis of all trials revealed a significant blood pressure-reducing effect of cocoa-chocolate compared with control (mean BP change +/- SE: SBP: -3.2 +/- 1.9 mmHg, P = 0.001; DBP: -2.0 +/- 1.3 mmHg, P = 0.003). However, subgroup meta analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 +/- 3.0 mmHg; P = 0.0009; DBP: -2.7 +/- 2.2 mm Hg, P = 0.01), while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 +/- 2.3 mmHg, P = 0.17; DBP: -1.3 +/- 1.6 mmHg, P = 0.12). Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30 mg to 1000 mg in the active treatment groups, and interventions ran for 2 to 18 weeks. Meta-regression analysis found study design and type of control to be borderline significant but possibly indirect predictors for blood pressure outcome. CONCLUSION: Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension. Flavanol-rich chocolate did not significantly reduce mean blood pressure below 140 mmHg systolic or 80 mmHg diastolic. PMID- 20584272 TI - Newly described human polyomaviruses Merkel cell, KI and WU are present in urban sewage and may represent potential environmental contaminants. AB - Recently, three new polyomaviruses (KI, WU and Merkel cell polyomavirus) have been reported to infect humans. It has also been suggested that lymphotropic polyomavirus, a virus of simian origin, infects humans. KI and WU polyomaviruses have been detected mainly in specimens from the respiratory tract while Merkel cell polyomavirus has been described in a very high percentage of Merkel cell carcinomas. The distribution, excretion level and transmission routes of these viruses remain unknown.Here we analyzed the presence and characteristics of newly described human polyomaviruses in urban sewage and river water in order to assess the excretion level and the potential role of water as a route of transmission of these viruses. Nested-PCR assays were designed for the sensitive detection of the viruses studied and the amplicons obtained were confirmed by sequencing analysis. The viruses were concentrated following a methodology previously developed for the detection of JC and BK human polyomaviruses in environmental samples. JC polyomavirus and human adenoviruses were used as markers of human contamination in the samples. Merkel cell polyomavirus was detected in 7/8 urban sewage samples collected and in 2/7 river water samples. Also one urine sample from a pregnant woman, out of 4 samples analyzed, was positive for this virus. KI and WU polyomaviruses were identified in 1/8 and 2/8 sewage samples respectively. The viral strains detected were highly homologous with other strains reported from several other geographical areas. Lymphotropic polyomavirus was not detected in any of the 13 sewage neither in 9 biosolid/sludge samples analyzed.This is the first description of a virus isolated from sewage and river water with a strong association with cancer. Our data indicate that the Merkel cell polyomavirus is prevalent in the population and that it may be disseminated through the fecal/urine contamination of water. The procedure developed may constitute a useful tool for studying the excreted strains, prevalence and transmission of these recently described polyomaviruses. PMID- 20584273 TI - Facilitators and barriers to implementing clinical care pathways. AB - BACKGROUND: The promotion of care pathways in the recent Governmental health policy reports of Lord Darzi is likely to increase efforts to promote the use of care pathways in the NHS. Evidence on the process of pathway implementation, however, is sparse and variations in how organisations go about the implementation process are likely to be large. This paper summarises what is known about factors which help or hinder clinicians in adopting and putting care pathways into practice, and which consequently promote or hinder the implementation of scientific evidence in clinical practice. DISCUSSION: Care pathways can provide patients with clear expectations of their care, provide a means of measuring patient's progress, promote teamwork on a multi-disciplinary team, facilitate the use of guidelines, and may act as a basis for a payment system. In order to achieve adequate implementation, however, facilitators and barriers must be considered, planned for, and incorporated directly into the pathway with full engagement among clinical and management staff. Barriers and/or facilitators may be present at each stage of development, implementation and evaluation; and, barriers at any stage can impede successful implementation. Important considerations to be made are ensuring the inclusion of all types of staff, plans for evaluating and incorporating continuous improvements, allowing for organisational adaptations and promoting the use of multifaceted interventions. SUMMARY: Although there is a dearth of information regarding the successful implementation of care pathways, evidence is available which may be applied when implementing a care pathway. Multifaceted interventions which incorporate all staff and facilitate organisational adaptations must be seriously considered and incorporated alongside care pathways in a continuous manner. In order to better understand the mechanism upon which care pathways are effective, however, more research specifically addressing conditions under which providers become engaged in using care pathways is needed. PMID- 20584274 TI - Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study. AB - BACKGROUND: Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC. METHODS: Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis. RESULTS: In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27).In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93).In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay ( 10) ANOVA with independent evaluator-rated symptom severity scores as the continuous dependent variable also detected no main effects for age or for any interactions involving age. In light of the small sample size, the mean symptom severity scores at weeks 0 and 8 for younger and older patients randomized to behavioral therapy were also plotted. Visual inspection of these data indicated that although the groups appeared to have started at similar levels of severity for children /= 10; the week 8 data show that the three younger children did at least as well as if not slightly better than the nine older children and adolescents. CONCLUSIONS: Behavior therapy for pediatric trichotillomania appears to be efficacious even in young children. The developmental and clinical implications of these findings will be discussed. TRIAL REGISTRATION: Clinicaltrials.gov NCT00043563. PMID- 20584277 TI - Health economics: the start of clinical freedom. AB - BACKGROUND: Since Professor Hampton announced the death of clinical freedom in 1983, the increasing influence of Evidence-based Medicine and Health Technology Assessment has contributed to augment the feeling that clinicians have a secondary role in the therapeutic decision-making process. DISCUSSION: This article constitutes a reflection on how clinicians may use the results of economic evaluations in their daily clinical practice, making decisions about cost-effectiveness on a case by case basis, and addressing both the patient's and society's needs. To that end, some illustrating examples are taken from the literature to show there are factors with great impact on cost-effectiveness results that can be easily identified and modified by clinicians. SUMMARY: The evolution of the discipline and the trend towards a tailored therapy suggest that health economics is not the end of clinical freedom but the start of it. PMID- 20584276 TI - Guidelines on uncomplicated urinary tract infections are difficult to follow: perceived barriers and suggested interventions. AB - BACKGROUND: Urinary tract infections (UTI) are among the most common health problems seen in general practice. Evidence-based guidelines on UTI are available, but adherence to these guidelines varies widely among practitioners for reasons not well understood. The aim of this study was to identify the barriers to the implementation of a guideline on UTI perceived by Dutch general practitioners (GPs) and to explore interventions to overcome these barriers. METHODS: A focus group study, including 13 GPs working in general practices in the Netherlands, was conducted. Key recommendations on diagnosis and treatment of uncomplicated UTI were selected from the guideline. Barriers to guideline adherence and possible interventions to address these barriers were discussed. The focus group session was audio-taped and transcribed verbatim. Barriers were classified according to an existing framework. RESULTS: Lack of agreement with the recommendations, unavailable and inconvenient materials (i.e. dipslides), and organisational constraints were perceived as barriers for the diagnostic recommendations. Barriers to implementing the treatment recommendations were lack of applicability and organisational constraints related to the availability of drugs in pharmacies. Suggested interventions were to provide small group education to GPs and practice staff members, to improve organisation and coordination of care in out of hour services, to improve the availability of preferred dosages of drugs, and to pilot-test guidelines regionally. CONCLUSIONS: Despite sufficient knowledge of the recommendations on UTI, attitudinal and external barriers made it difficult to follow them in practice. The care concerning UTI could be optimized if these barriers are adequately addressed in implementation strategies. The feasibility and success of these strategies could be improved by involving the target group of the guideline in selecting useful interventions to address the barriers to implementation. PMID- 20584278 TI - On the resuscitation of clinical freedom. AB - BACKGROUND: This paper is a response to the suggestion by Sacristan et al that clinicians can increase their clinical freedom by undertaking individualised economic analyses that demonstrate that interventions, which at a population level do not reach conventional thresholds of cost-effectiveness, do so in particular patients. DISCUSSION: In this reply, I question the presumption that "clinical freedom" is necessarily desirable and go on to argue that, even if it is, the proposal that clinicians should do individualised economic evaluation is flawed. Firstly, the additional clinical choice that may be gained from individualised economic analyses that demonstrate that an intervention, generally considered not to be cost-effective, is cost-effective in a particular patient, is likely to be counterbalanced by other analyses that produce the converse result (i.e. that an intervention that is cost-effective at a population level may not be so in a particular patient)--a complementary consequence, which is ignored by Sacristan et al in their paper. Secondly, the skills and time required to do an individualised economic analysis are likely to exceed those of most clinicians. Thirdly, and most importantly, asking clinicians to make rationing judgements at the point of care is a threat to patient trust and can harm the doctor-patient relationship. SUMMARY: Individualised economic evaluations are neither a desirable nor feasible method for increasing clinical choice. PMID- 20584279 TI - Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans. AB - BACKGROUND: The gene daf-2 encodes the single insulin/insulin growth factor-1 like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. RESULTS: We found that the e1370 mutation alters aerobic energy production substantially. In wild type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370) adult animals. The increase in daf-2(e1370) mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370) animals. CONCLUSIONS: We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function. PMID- 20584280 TI - Treatment choices for fevers in children under-five years in a rural Ghanaian district. AB - BACKGROUND: Health care demand studies help to examine the behaviour of individuals and households during illnesses. Few of existing health care demand studies examine the choice of treatment services for childhood illnesses. Besides, in their analyses, many of the existing studies compare alternative treatment options to a single option, usually self-medication. This study aims at examining the factors that influence the choices that caregivers of children under-five years make regarding treatment of fevers due to malaria and pneumonia in a rural setting. The study also examines how the choice of alternative treatment options compare with each other. METHODS: The study uses data from a 2006 household socio-economic survey and health and demographic surveillance covering caregivers of 529 children under-five years of age in the Dangme West District and applies a multinomial probit technique to model the choice of treatment services for fevers in under-fives in rural Ghana. Four health care options are considered: self-medication, over-the-counter providers, public providers and private providers. RESULTS: The findings indicate that longer travel, waiting and treatment times encourage people to use self-medication and over-the-counter providers compared to public and private providers. Caregivers with health insurance coverage also use care from public providers compared to over-the-counter or private providers. Caregivers with higher incomes use public and private providers over self-medication while higher treatment charges and longer times at public facilities encourage caregivers to resort to private providers. Besides, caregivers of female under-fives use self-care while caregivers of male under-fives use public providers instead of self-care, implying gender disparity in the choice of treatment. CONCLUSIONS: The results of this study imply that efforts at curbing under-five mortality due to malaria and pneumonia need to take into account care-seeking behaviour of caregivers of under fives as well as implementation of strategies. PMID- 20584281 TI - Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. AB - BACKGROUND: The diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings. METHODS: KYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR. RESULTS: High expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026). The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0 2A tumors (p = 0.049). When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression), the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065). Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029). The survival rate of patients from the high expression group (n = 10) was lower than that in the low expression group (n = 11), and all the patients in the low VEGF-C expression group survived. CONCLUSIONS: The expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node. PMID- 20584282 TI - The impact of a standardised intramuscular sedation protocol for acute behavioural disturbance in the emergency department. AB - BACKGROUND: Acute behavioural disturbance (ABD) is an increasing problem in emergency departments. This study aimed to determine the impact of a structured intramuscular (IM) sedation protocol on the duration of ABD in the emergency department. METHODS: A historical control study was undertaken comparing 58 patients who required physical restraint and parenteral sedation with the structured IM sedation protocol, to 73 historical controls treated predominantly by intravenous sedation, according to individual clinician preference. The primary outcome was the duration of the ABD defined as the time security staff were required. Secondary outcomes were the requirement for additional sedation, drug related-adverse effects and patient and staff injuries. RESULTS: The median duration of the ABD in patients with the new sedation protocol was 21 minutes (IQR: 15 to 35 minutes; Range: 5 to 78 minutes) compared to a median duration of 30 minutes (IQR: 15 to 50 minutes; Range: 5 to 135 minutes) in the historical controls which was significantly different (p = 0.03). With IM sedation only 27 of 58 patients (47%; 95% CI: 34% to 60%) required further sedation compared to 64 of 73 historical controls (88%; 95%CI: 77% to 94%). There were six (10%) drug related adverse events with the new IM protocol [oxygen desaturation (5), oxygen desaturation/airway obstruction (1)] compared to 10 (14%) in the historical controls [oxygen desaturation (5), hypoventilation (4) and aspiration (1)]. Injuries to staff occurred with three patients using the new sedation protocol and in seven of the historical controls. Two patients were injured during the new protocol and two of the historical controls. CONCLUSION: The use of a standardised IM sedation protocol was simple, more effective and as safe for management of ABD compared to predominantly intravenous sedation. PMID- 20584283 TI - Clinical consequences of road traffic injuries among the elderly in Japan. AB - BACKGROUND: Road traffic injuries among the elderly have recently become a public health issue; therefore, we investigated the clinical characteristics of such injuries among the elderly in Japan. METHODS: A retrospective study was performed using data from a medium-sized hospital emergency department. Data were extracted from medical records for one year, and patients were categorized into groups ages 18-64, 65-74 and 75+. Variables included demographic characteristics, injury circumstances, and nature of injury. Univariate and bivariate descriptive statistical analyses were performed, and multivariate logistic regression was used to evaluate injury severity and hospital admission by age groups. RESULTS: A total of 1,656 patients were studied. Patients aged 65+ had more chest wall injury, intracranial injury, lower extremity fracture, and intrathoracic injury than patients aged 18-64. CONCLUSIONS: Injury circumstances and nature of injuries associated with traffic incidents showed different patterns by age groups, particularly among the elderly. PMID- 20584284 TI - Clinical use of biomarkers of survival in pulmonary fibrosis. AB - BACKGROUND: Biologic predictors or biomarkers of survival in pulmonary fibrosis with a worse prognosis, more specifically in idiopathic pulmonary fibrosis would help the clinician in deciding whether or not to treat since treatment carries a potential risk for adverse events. These decisions are made easier if accurate and objective measurements of the patients' clinical status can predict the risk of progression to death. METHOD: A literature review is given on different biomarkers of survival in interstitial lung disease, mainly in IPF, since this disease has the worst prognosis. CONCLUSION: Serum biomarkers, and markers measured by medical imaging as HRCT, pertechnegas, DTPA en FDG-PET are not ready for clinical use to predict mortality in different forms of ILD. A baseline FVC, a change of FVC of more than 10%, and change in 6MWD are clinically helpful predictors of survival. PMID- 20584285 TI - Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas. AB - BACKGROUND: Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed. METHODS: sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC. RESULTS: At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5 81.0%). CONCLUSIONS: Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary. PMID- 20584286 TI - Coordinated transcriptional regulation of two key genes in the lignin branch pathway--CAD and CCR--is mediated through MYB- binding sites. AB - BACKGROUND: Cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the final steps in the biosynthesis of monolignols, the monomeric units of the phenolic lignin polymers which confer rigidity, imperviousness and resistance to biodegradation to cell walls. We have previously shown that the Eucalyptus gunnii CCR and CAD2 promoters direct similar expression patterns in vascular tissues suggesting that monolignol production is controlled, at least in part, by the coordinated transcriptional regulation of these two genes. Although consensus motifs for MYB transcription factors occur in most gene promoters of the whole phenylpropanoid pathway, functional evidence for their contribution to promoter activity has only been demonstrated for a few of them. Here, in the lignin-specific branch, we studied the functional role of MYB elements as well as other cis-elements identified in the regulatory regions of EgCAD2 and EgCCR promoters, in the transcriptional activity of these gene promoters. RESULTS: By using promoter deletion analysis and in vivo footprinting, we identified an 80 bp regulatory region in the Eucalyptus gunnii EgCAD2 promoter that contains two MYB elements, each arranged in a distinct module with newly identified cis-elements. A directed mutagenesis approach was used to introduce block mutations in all putative cis-elements of the EgCAD2 promoter and in those of the 50 bp regulatory region previously delineated in the EgCCR promoter. We showed that the conserved MYB elements in EgCAD2 and EgCCR promoters are crucial both for the formation of DNA-protein complexes in EMSA experiments and for the transcriptional activation of EgCAD2 and EgCCR promoters in vascular tissues in planta. In addition, a new regulatory cis-element that modulates the balance between two DNA-protein complexes in vitro was found to be important for EgCAD2 expression in the cambial zone. CONCLUSIONS: Our assignment of functional roles to the identified cis elements clearly demonstrates the importance of MYB cis-elements in the transcriptional regulation of two genes of the lignin-specific pathway and support the hypothesis that MYB elements serve as a common means for the coordinated regulation of genes in the entire lignin biosynthetic pathway. PMID- 20584287 TI - Home-based chlamydia testing of young people attending a music festival--who will pee and post? AB - BACKGROUND: Chlamydia is most common among young people, but only a small proportion of Australian young people are tested annually. Home-based chlamydia testing has been piloted in several countries to increase testing rates, but uptake has been low. We aimed to identify predictors of uptake of home-based chlamydia testing to inform future testing programs. METHODS: We offered home based chlamydia testing kits to participants in a sexual behaviour cross sectional survey conducted at a music festival in Melbourne, Australia. Those who consented received a testing kit and were asked to return their urine or vaginal swab sample via post. RESULTS: Nine hundred and two sexually active music festival attendees aged 16-29 completed the survey; 313 (35%) opted to receive chlamydia testing kits, and 67 of 313 (21%) returned a specimen for testing. One participant was infected with chlamydia (1% prevalence). Independent predictors of consenting to receive a testing kit included older age, knowing that chlamydia can make women infertile, reporting more than three lifetime sexual partners and inconsistent condom use. Independent predictors of returning a sample to the laboratory included knowing that chlamydia can be asymptomatic, not having had an STI test in the past six months and not living with parents. CONCLUSIONS: A low proportion of participants returned their chlamydia test, suggesting that this model is not ideal for reaching young people. Home-based chlamydia testing is most attractive to those who report engaging in sexual risk behaviours and are aware of the often asymptomatic nature and potential sequelae of chlamydia infection. PMID- 20584288 TI - A qualitative study of naturopathy in rural practice: a focus upon naturopaths' experiences and perceptions of rural patients and demands for their services. AB - BACKGROUND: Complementary and alternative medicine (CAM) use--of which naturopathy constitutes a significant proportion--accounts for approximately half of all health consultations and half of out-of-pocket expenditure in Australia. Data also suggest CAM use is highest amongst rural Australians. Unfortunately little is known about the grass-roots reality of naturopathy or other CAM use in rural regions. METHODS: Semi-structured interviews were conducted with 20 naturopaths practising in the Darling Downs region of South-East Queensland to assess their perceptions and experiences of rural patients and demand for their services. RESULTS: Naturopaths described strong demand in rural areas for their services and perceived much of this demand as attributable to cultural traits in rural communities that served as pull factors for their naturopathic services. Such perceived traits included a cultural affinity for holistic approaches to health and disease and the preventive philosophy of naturopathy and an appreciation of the core tenet of naturopathic practice to develop closer therapeutic relationships. However, cost and a rural culture of self-reliance were seen as major barriers to naturopathic practice in rural areas. CONCLUSIONS: Demand for naturopathic services in rural areas may have strong underlying cultural and social drivers. Given the apparent affinity for and increasingly large role played by CAM services, including naturopathic medicine, in rural areas it is imperative that naturopathic medicine and the CAM sector more broadly become a core focus of rural health research. PMID- 20584289 TI - A novel allele of FILAMENTOUS FLOWER reveals new insights on the link between inflorescence and floral meristem organization and flower morphogenesis. AB - BACKGROUND: The Arabidopsis FILAMENTOUS FLOWER (FIL) gene encodes a YABBY (YAB) family putative transcription factor that has been implicated in specifying abaxial cell identities and thus regulating organ polarity of lateral organs. In contrast to double mutants of fil and other YAB genes, fil single mutants display mainly floral and inflorescence morphological defects that do not reflect merely a loss of abaxial identity. Recently, FIL and other YABs have been shown to regulate meristem organization in a non-cell-autonomous manner. In a screen for new mutations affecting floral organ morphology and development, we have identified a novel allele of FIL, fil-9 and characterized its floral and meristem phenotypes. RESULTS: The fil-9 mutation results in highly variable disruptions in floral organ numbers and size, partial homeotic transformations, and in defective inflorescence organization. Examination of meristems indicates that both fil-9 inflorescence and floral meristems are enlarged as a result of an increase in cell number, and deformed. Furthermore, primordia emergence from these meristems is disrupted such that several primordia arise simultaneously instead of sequentially. Many of the organs produced by the inflorescence meristems are filamentous, yet they are not considered by the plant as flowers. The severity of both floral organs and meristem phenotypes is increased acropetally and in higher growth temperature. CONCLUSIONS: Detailed analysis following the development of fil-9 inflorescence and flowers throughout flower development enabled the drawing of a causal link between multiple traits of fil-9 phenotypes. The study reinforces the suggested role of FIL in meristem organization. The loss of spatial and temporal organization of fil-9 inflorescence and floral meristems presumably leads to disrupted cell allocation to developing floral organs and to a blurring of organ whorl boundaries. This disruption is reflected in morphological and organ identity aberrations of fil-9 floral organs and in the production of filamentous organs that are not perceived as flowers. Here, we show the role of FIL in reproductive meristem development and emphasize the potential of using fil mutants to study mersitem organization and the related effects on flower morphogenesis. PMID- 20584290 TI - Targeting the angiotensin II type 2 receptor (AT2R) in colorectal liver metastases. AB - BACKGROUND: Blockade of the angiotensin (ANG) II type 1 receptor (AT1R) inhibits tumour growth in several cancers, including colorectal cancer (CRC) liver metastases. While AT1R blockade has been extensively studied, the potential of targeting the antagonistically acting AT2R in cancer has not been investigated. This study examined the effect of AT2R activation with the agonist CGP42112A in a mouse model of CRC liver metastases. RESULTS: In vitro, mouse CRC cell (MoCR) proliferation was inhibited by treatment with CGP42112A in a dose dependent manner while apoptosis was increased. Immunofluorescent staining for key signalling and secondary messengers, PLA2 and iNOS, were also increased by CGP42112A treatment in vitro. Immunohistochemical staining for proliferation (PCNA) and the apoptosis (active caspase 3) markers confirmed a CGP42112A associated inhibition of proliferation and induction of apoptosis of mouse CRC cells (MoCR) in vivo. However, angiogenesis and vascular endothelial growth factor (VEGF) appeared to be increased by CGP42112A treatment in vivo. This increase in VEGF secretion by MoCRs was confirmed in vitro. Despite this apparent pro-angiogenic effect, a syngenic orthotopic mouse model of CRC liver metastases showed a reduction in liver to body weight ratio, an indication of tumour burden, following CGP42112A treatment compared to untreated controls. CONCLUSIONS: These results suggest that AT2R activation might provide a novel target to inhibit tumour growth. Its potential to stimulate angiogenesis could be compensated by combination with anti-angiogenic agents. PMID- 20584291 TI - Early fluid resuscitation with hyperoncotic hydroxyethyl starch 200/0.5 (10%) in severe burn injury. AB - INTRODUCTION: Despite large experience in the management of severe burn injury, there are still controversies regarding the best type of fluid resuscitation, especially during the first 24 hours after the trauma. Therefore, our study addressed the question whether hyperoncotic hydroxyethyl starch (HES) 200/0.5 (10%) administered in combination with crystalloids within the first 24 hours after injury is as effective as 'crystalloids only' in severe burn injury patients. METHODS: 30 consecutive patients were enrolled to this prospective interventional open label study and assigned either to a traditional 'crystalloids only' or to a 'HES 200/0.5 (10%)' volume resuscitation protocol. Total amount of fluid administration, complications such as pulmonary failure, abdominal compartment syndrome, sepsis, renal failure and overall mortality were assessed. Cox proportional hazard regression analysis was performed for binary outcomes and adjustment for potential confounders was done in the multivariate regression models. For continuous outcome parameters multiple linear regression analysis was used. RESULTS: Group differences between patients receiving crystalloids only or HES 200/0.5 (10%) were not statistically significant. However, a large effect towards increased overall mortality (adjusted hazard ratio 7.12; P = 0.16) in the HES 200/0.5 (10%) group as compared to the crystalloids only group (43.8% versus 14.3%) was present. Similarly, the incidence of renal failure was 25.0% in the HES 200/0.5 (10%) group versus 7.1% in the crystalloid only group (adjusted hazard ratio 6.16; P = 0.42). CONCLUSIONS: This small study indicates that the application of hyperoncotic HES 200/0.5 (10%) within the first 24 hours after severe burn injury may be associated with fatal outcome and should therefore be used with caution. TRIAL REGISTRATION: NCT01120730. PMID- 20584292 TI - Meta-analysis of cotton fiber quality QTLs across diverse environments in a Gossypium hirsutum x G. barbadense RIL population. AB - BACKGROUND: Cotton fibers (produced by Gossypium species) are the premier natural fibers for textile production. The two tetraploid species, G. barbadense (Gb) and G. hirsutum (Gh), differ significantly in their fiber properties, the former having much longer, finer and stronger fibers that are highly prized. A better understanding of the genetics and underlying biological causes of these differences will aid further improvement of cotton quality through breeding and biotechnology. We evaluated an inter-specific Gh x Gb recombinant inbred line (RIL) population for fiber characteristics in 11 independent experiments under field and glasshouse conditions. Sites were located on 4 continents and 5 countries and some locations were analyzed over multiple years. RESULTS: The RIL population displayed a large variability for all major fiber traits. QTL analyses were performed on a per-site basis by composite interval mapping. Among the 651 putative QTLs (LOD > 2), 167 had a LOD exceeding permutation based thresholds. Coincidence in QTL location across data sets was assessed for the fiber trait categories strength, elongation, length, length uniformity, fineness/maturity, and color. A meta-analysis of more than a thousand putative QTLs was conducted with MetaQTL software to integrate QTL data from the RIL and 3 backcross populations (from the same parents) and to compare them with the literature. Although the global level of congruence across experiments and populations was generally moderate, the QTL clustering was possible for 30 trait x chromosome combinations (5 traits in 19 different chromosomes) where an effective co localization of unidirectional (similar sign of additivity) QTLs from at least 5 different data sets was observed. Most consistent meta-clusters were identified for fiber color on chromosomes c6, c8 and c25, fineness on c15, and fiber length on c3. CONCLUSIONS: Meta-analysis provided a reliable means of integrating phenotypic and genetic mapping data across multiple populations and environments for complex fiber traits. The consistent chromosomal regions contributing to fiber quality traits constitute good candidates for the further dissection of the genetic and genomic factors underlying important fiber characteristics, and for marker-assisted selection. PMID- 20584293 TI - Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development. AB - BACKGROUND: The Mexican axolotl (Ambystoma mexicanum) is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic) form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum) that typically undergo a metamorphosis. RESULTS: Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph) and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs) were identified as unique to the axolotl (n = 76) and tiger salamander (n = 292) than were identified as shared (n = 108). All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times. CONCLUSIONS: Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome-wide reduction in mRNA abundance across loci, including genes that regulate hypothalamic-pituitary activities. This suggests that an axolotls failure to undergo anatomical metamorphosis late in the larval period is indirectly associated with a mechanism(s) that acts earlier in development to broadly program transcription. The axolotl hopeful monster provides a model to identify mechanisms of early brain development that proximally and ultimately affect the expression of adult phenotypes. PMID- 20584294 TI - Anaemia and low birth weight in Medani, Hospital Sudan. AB - BACKGROUND: Reducing the incidence of Low birth weight (LBW) neonates by at least one third between 2000 and 2010 is one of the major goals of the United Nations resolution "A World Fit for Children". This was a case-control study conducted between August-October 2009 in Medani Hospital, Sudan to investigate the risk factors for LBW. Cases were mothers who delivered singleton baby < 2500 gm. Controls were mothers delivered singleton baby of >/= 2500 gm. FINDINGS: Out of 1224 deliveries, 97 (12.6%) of the neonates were LBW deliveries. While maternal socio-demographic characteristics (age, parity and mother education) and anthropometrics measurements were not associated with LBW, lack of antenatal care (OR = 5.9, 95% CI = 1.4-24.4; P = 0.01) and maternal anaemia (OR = 9.0, 95% CI = 3.4-23.8; P < 0.001) were the main risk factor for LBW. CONCLUSION: Thus, more care on antenatal care and nutrition may prevent LBW. PMID- 20584295 TI - Identifying differentially regulated subnetworks from phosphoproteomic data. AB - BACKGROUND: Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation). Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action. RESULTS: Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor. CONCLUSIONS: SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data. PMID- 20584296 TI - A study of HIV/AIDS related knowledge, attitude and behaviors among female sex workers in Shanghai China. AB - BACKGROUND: China is currently facing a rapid and widespread increase in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The activities of female sex workers (FSWs) have contributed to the mounting epidemic of HIV/AIDS and other sexually transmitted diseases (STDs). Therefore, this study aimed to assess the HIV/AIDS-related knowledge, attitude and risk behaviors among FSWs operating in Shanghai China. METHODS: A cross-sectional study was conducted in five districts of Shanghai, including three suburbs and two downtown locales. We adopted a cluster randomized sampling method to obtain ten geographic sites which consisted of one or more communities/villages proximal to a location where FSWs were accessible. A total of 324 FSWs from 109 Xitou Fang, massage parlors and hair salons who explicitly provided sexual services were enrolled in the study. Each participant completed a questionnaire survey and interview aimed to collect information on the individual's knowledge, attitude, and behaviors associated with risk for HIV/AIDs. RESULTS: The overall correct answer rate of HIV/AIDS-related knowledge was 60.8%, and the knowledge of FSWs from downtown areas was significantly higher than those from suburban areas (P < 0.05). The percentage of FSWs who reported having experiences in commercial sexual services without the use of condoms was 33.6%. Condom slippage or breakage was reported as having occurred at least once by 51.2% of the FSWs. FSWs from suburban areas were found to more often engage in high-risk behaviors, including oral and anal sex, than those from downtown areas (P < 0.001). Many of the FSWs (65.7%) reported having non-client sexual partners (most were identified as boyfriends or husbands); however, condom usage with these partners were lower (34.3%). CONCLUSIONS: Based on the findings from our survey, we advise that promotion of HIV/AIDS-related knowledge be targeted towards FSWs in Shanghai, especially those operating in the suburbs. HIV prevention efforts, such as urging constant condom usage with both clients and steady partners, should be sustained and reinforced among the female sex workers population. PMID- 20584297 TI - Task-related modulation of anterior theta and posterior alpha EEG reflects top down preparation. AB - BACKGROUND: Prestimulus EEG alpha activity in humans has been considered to reflect ongoing top-down preparation for the performance of subsequent tasks. Since theta oscillations may be related to poststimulus top-down processing, we investigated whether prestimulus EEG theta activity also reflects top-down cognitive preparation for a stimulus. RESULTS: We recorded EEG data from 15 healthy controls performing a color and shape discrimination task, and used the wavelet transformation to investigate the time course and power of oscillatory activity in the signals. We observed a relationship between both anterior theta and posterior alpha power in the prestimulus period and the type of subsequent task. CONCLUSIONS: Since task-differences were reflected in both theta and alpha activities prior to stimulus onset, both prestimulus theta (particularly around the anterior region) and prestimulus alpha (particularly around the posterior region) activities may reflect prestimulus top-down preparation for the performance of subsequent tasks. PMID- 20584298 TI - Evolutionary patterns at the RNase based gametophytic self - incompatibility system in two divergent Rosaceae groups (Maloideae and Prunus). AB - BACKGROUND: Within Rosaceae, the RNase based gametophytic self-incompatibility (GSI) system has been studied at the molecular level in Maloideae and Prunus species that have been diverging for, at least, 32 million years. In order to understand RNase based GSI evolution within this family, comparative studies must be performed, using similar methodologies. RESULT: It is here shown that many features are shared between the two species groups such as levels of recombination at the S-RNase (the S-pistil component) gene, and the rate at which new specificities arise. Nevertheless, important differences are found regarding the number of ancestral lineages and the degree of specificity sharing between closely related species. In Maloideae, about 17% of the amino acid positions at the S-RNase protein are found to be positively selected, and they occupy about 30% of the exposed protein surface. Positively selected amino acid sites are shown to be located on either side of the active site cleft, an observation that is compatible with current models of specificity determination. At positively selected amino acid sites, non-conservative changes are almost as frequent as conservative changes. There is no evidence that at these sites the most drastic amino acid changes may be more strongly selected. CONCLUSIONS: Many similarities are found between the GSI system of Prunus and Maloideae that are compatible with the single origin hypothesis for RNase based GSI. The presence of common features such as the location of positively selected amino acid sites and lysine residues that may be important for ubiquitylation, raise a number of issues that, in principle, can be experimentally addressed in Maloideae. Nevertheless, there are also many important differences between the two Rosaceae GSI systems. How such features changed during evolution remains a puzzling issue. PMID- 20584299 TI - Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer. AB - BACKGROUND: Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer. METHODS: Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m2/day was administered on each day of irradiation. RESULTS: Twenty six measurable lesions were evaluated. Overall in field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand foot syndrome (one patient) and grade 1/2 fatigue (three patients). CONCLUSIONS: Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses. PMID- 20584300 TI - Dietary n-3:n-6 fatty acid ratios differentially influence hormonal signature in a rodent model of metabolic syndrome relative to healthy controls. AB - Dietary ratios of omega-3 (n-3) to omega-6 (n-6) polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of the metabolic syndrome, including insulin sensitivity, inflammation, lipid profiles and adiposity. However, the role of dietary PUFAs in regulating energy systems in healthy relative to metabolic diseased backgrounds has not been systematically addressed. We used dietary manipulation of n-3 to n-6 PUFA ratios in an animal model of metabolic syndrome and a related healthy line to assay feeding behavior and endocrine markers of feeding drive and energy regulation. Two related lines of rodents with a healthy and a metabolic syndrome phenotype were fed one of two isocaloric diets, comprised of either a 1:1 or a 1:30 n-3 to n-6 ratio, for 30 days. Food intake and weight gain were monitored; and leptin, ghrelin, adiponectin and a suite of hypothalamic neuropeptides involved in energy regulation were assayed following the dietary manipulation period. There was no difference in caloric intake or weight gain between diet groups, however there was a significant interaction between diet and phenotypic line on central and peripheral markers of energy homeostasis. Thus serum levels of leptin, acylated ghrelin and adiponectin, and mRNA levels of the anorexigenic hypothalamic neuropeptide, cocaine-amphetamine related transcript (CART), showed differential, dietary responses with HCR rats showing an increase in anorexigenic signals in response to unbalanced n-3:6 ratios, while LCR did not. These data are the first to demonstrate that a rodent line with a metabolic syndrome-like phenotype responds differentially to dietary manipulation of n-3 and n-6 fatty acids relative to a related healthy line with regard to endocrine markers of energy homeostasis. The dietary n-3:n-6 ratios used in this experiment represent extreme points of natural human diets, however the data suggest that optimal recommendations regarding omega-3 and omega-6 intake may have differing effects in healthy subjects relative to metabolic syndrome patients. Further research is necessary to establish these responses in human populations. PMID- 20584301 TI - Accumulated coercion and short-term outcome of inpatient psychiatric care. AB - BACKGROUND: The knowledge of the impact of coercion on psychiatric treatment outcome is limited. Multiple measures of coercion have been recommended. The aim of the study was to examine the impact of accumulated coercive incidents on short term outcome of inpatient psychiatric care METHODS: 233 involuntarily and voluntarily admitted patients were interviewed within five days of admission and at discharge or after maximum three weeks of care. Coercion was measured as number of coercive incidents, i.e. subjectively reported and in the medical files recorded coercive incidents, including legal status and perceived coercion at admission, and recorded and reported coercive measures during treatment. Outcome was measured both as subjective improvement of mental health and as improvement in professionally assessed functioning according to GAF. Logistic regression analyses were performed with patient characteristics and coercive incidents as independent and the two outcome measures as dependent variables RESULTS: Number of coercive incidents did not predict subjective or assessed improvement. Patients having other diagnoses than psychoses or mood disorders were less likely to be subjectively improved, while a low GAF at admission predicted an improvement in GAF scores CONCLUSION: The results indicate that subjectively and professionally assessed mental health short-term outcome of acute psychiatric hospitalisation are not predicted by the amount of subjectively and recorded coercive incidents. Further studies are needed to examine the short- and long term effects of coercive interventions in psychiatric care. PMID- 20584302 TI - New clinically relevant, orthotopic mouse models of human chondrosarcoma with spontaneous metastasis. AB - BACKGROUND: Chondrosarcoma responds poorly to adjuvant therapy and new, clinically relevant animal models are required to test targeted therapy. METHODS: Two human chondrosarcoma cell lines, JJ012 and FS090, were evaluated for proliferation, colony formation, invasion, angiogenesis and osteoclastogenesis. Cell lines were also investigated for VEGF, MMP-2, MMP-9, and RECK expression. JJ012 and FS090 were injected separately into the mouse tibia intramedullary canal or tibial periosteum. Animal limbs were measured, and x-rayed for evidence of tumour take and progression. Tibias and lungs were harvested to determine the presence of tumour and lung metastases. RESULTS: JJ012 demonstrated significantly higher proliferative capacity, invasion, and colony formation in collagen I gel. JJ012 conditioned medium stimulated endothelial tube formation and osteoclastogenesis with a greater potency than FS090 conditioned medium, perhaps related to the effects of VEGF and MMP-9. In vivo, tumours formed in intratibial and periosteal groups injected with JJ012, however no mice injected with FS090 developed tumours. JJ012 periosteal tumours grew to 3 times the non-injected limb size by 7 weeks, whereas intratibial injected limbs required 10 weeks to achieve a similar tumour size. Sectioned tumour tissue demonstrated features of grade III chondrosarcoma. All JJ012 periosteal tumours (5/5) resulted in lung micro metastases, while only 2/4 JJ012 intratibial tumours demonstrated metastases. CONCLUSIONS: The established JJ012 models replicate the site, morphology, and many behavioural characteristics of human chondrosarcoma. Local tumour invasion of bone and spontaneous lung metastasis offer valuable assessment tools to test the potential of novel agents for future chondrosarcoma therapy. PMID- 20584303 TI - Quality of life of adolescents with cancer: family risks and resources. AB - PURPOSE: The goal of this study was to evaluate the relative contribution of treatment intensity, family sociodemographic risk, and family resources to health related quality of life (QOL) of 102 adolescents in treatment for cancer. METHODS: Adolescents and parents completed self-report measures of teen QOL, family functioning, and parent-child bonding. Based on parent report of family sociodemographic variables, an additive risk index was computed. A pediatric oncologist rated treatment intensity. RESULTS: Simultaneous regression analyses demonstrated the significant contribution of roles in family functioning and quality of parent-child relationship to prediction of psychosocial QOL (parent and teen-reported) as well as parent-reported teen physical QOL over and above the contribution of treatment intensity. Family sociodemographic risk did not contribute to QOL in these regression analyses. In additional analyses, specific diagnosis, types of treatment and individual sociodemographic risk variables were not associated with QOL. Parent and teen ratings of family functioning and quality of life were concordant. CONCLUSIONS: Family functioning, including quality of parent-child relationship, are central and potentially modifiable resistance factors in teen QOL while under treatment for cancer. Even more important than relying on diagnosis or treatment, screening for roles and relationships early in treatment may be an important aspect of determining risk for poor QOL outcomes. PMID- 20584304 TI - Protein docking by Rotation-Based Uniform Sampling (RotBUS) with fast computing of intermolecular contact distance and residue desolvation. AB - BACKGROUND: Protein-protein interactions are fundamental for the majority of cellular processes and their study is of enormous biotechnological and therapeutic interest. In recent years, a variety of computational approaches to the protein-protein docking problem have been reported, with encouraging results. Most of the currently available protein-protein docking algorithms are composed of two clearly defined parts: the sampling of the rotational and translational space of the interacting molecules, and the scoring and clustering of the resulting orientations. Although this kind of strategy has shown some of the most successful results in the CAPRI blind test http://www.ebi.ac.uk/msd-srv/capri, more efforts need to be applied. Thus, the sampling protocol should generate a pool of conformations that include a sufficient number of near-native ones, while the scoring function should discriminate between near-native and non-near-native proposed conformations. On the other hand, protocols to efficiently include full flexibility on the protein structures are increasingly needed. RESULTS: In these work we present new computational tools for protein-protein docking. We describe here the RotBUS (Rotation-Based Uniform Sampling) method to generate uniformly distributed sets of rigid-body docking poses, with a new fast calculation of the optimal contacting distance between molecules. We have tested the method on a standard benchmark of unbound structures and we can find near-native solutions in 100% of the cases. After applying a new fast filtering scheme based on residue based desolvation, in combination with FTDock plus pyDock scoring, near-native solutions are found with rank 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. CONCLUSIONS: Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML. PMID- 20584306 TI - Primary follicular lymphoma of the fallopian tube found incidentally in a patient treated for endometrial carcinoma: a case report. AB - We report a rare case of primary lymphoma of fallopian tube in a 68-year-old woman who underwent total hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. The specimen showed a well-differentiated endometrioid adenocarcinoma with superficial myometrial invasion. The left fallopian tube revealed a 1 cm nodule that histologically showed diffuse lymphoid follicles consisting of small cleaved lymphocytes and occasional larger cells. The cells were immunopositive for CD20, BCL-2, and BCL-6 but negative for CD3 and CD43. Polymerase chain reaction confirmed a monoclonal B-cell population. Fluorescence in-situ hybridization revealed at (14, 18) translocation. The patient had absent lymphadenopathy and negative CT scan of chest, abdomen, and pelvis. The findings were consistent with a primary low grade follicular lymphoma of fallopian tube. She did not receive chemotherapy and remained disease free for 13 months after surgery. Our case suggests that primary lymphoma of fallopian tube may be associated with a favorable prognosis. PMID- 20584307 TI - Innovative gait robot for the repetitive practice of floor walking and stair climbing up and down in stroke patients. AB - BACKGROUND: Stair climbing up and down is an essential part of everyday's mobility. To enable wheelchair-dependent patients the repetitive practice of this task, a novel gait robot, G-EO-Systems (EO, Lat: I walk), based on the end effector principle, has been designed. The trajectories of the foot plates are freely programmable enabling not only the practice of simulated floor walking but also stair climbing up and down. The article intended to compare lower limb muscle activation patterns of hemiparetic subjects during real floor walking and stairs climbing up, and during the corresponding simulated conditions on the machine, and secondly to demonstrate gait improvement on single case after training on the machine. METHODS: The muscle activation pattern of seven lower limb muscles of six hemiparetic patients during free and simulated walking on the floor and stair climbing was measured via dynamic electromyography. A non ambulatory, sub-acute stroke patient additionally trained on the G-EO-Systems every workday for five weeks. RESULTS: The muscle activation patterns were comparable during the real and simulated conditions, both on the floor and during stair climbing up. Minor differences, concerning the real and simulated floor walking conditions, were a delayed (prolonged) onset (duration) of the thigh muscle activation on the machine across all subjects. Concerning stair climbing conditions, the shank muscle activation was more phasic and timely correct in selected patients on the device. The severely affected subject regained walking and stair climbing ability. CONCLUSIONS: The G-EO-Systems is an interesting new option in gait rehabilitation after stroke. The lower limb muscle activation patterns were comparable, a training thus feasible, and the positive case report warrants further clinical studies. PMID- 20584308 TI - Spontaneous dural tear leading to intracranial hypotension and tonsillar herniation in Marfan syndrome: a case report. AB - BACKGROUND: We describe the case of a 38 year old male with Marfan syndrome who presented with orthostatic headaches and seizures. CASE PRESENTATION: The patient was diagnosed with Spontaneous Intracranial Hypotension secondary to CSF leaks, objectively demonstrated by MR myelogram with intrathecal contrast. Epidural autologous blood patch was administered at the leakage site leading to significant improvement. CONCLUSION: Our literature search shows that this is the second reported case of a Marfan patient presenting with symptomatic spontaneous CSF leaks along with tonsillar herniation. PMID- 20584309 TI - Uterine primitive neuroectodermal tumor with adenosarcoma: a case report. AB - INTRODUCTION: Primitive neuroectodermal tumor of the uterus is extremely rare. They occur as either pure primitive neuroectodermal tumors or admixed with neoplasms of mullerian origin. CASE PRESENTATION: A case of uterine primitive neuroectodermal tumor with adenosarcoma in a 50-year-old Asian Indian woman is presented. Histologically, the neoplasm displayed perivascular pseudorosettes and occasional Homer-Wright rosettes. A strong positivity for neuronspecific enolase and synaptophysin was noted, while chromogranin and CD99 were negative. Merging imperceptibly with the neuroectodermal components were the areas of adenosarcoma. CONCLUSION: To the best of our knowledge, this report represents the second case of a uterine primitive neuroectodermal tumor with an admixed adenosarcoma. PMID- 20584311 TI - Complicated sternal dehiscence treated with the strasbourg thoracic osteosyntheses system (STRATOS) and the transposition of greater omentum: a case report. AB - Sternal dehiscence is a serious complication after cardiac surgery. Sternal refixation, performed by simple rewiring or techniqual modification of rewiring as described by Robicsek, can fail, overall when the bone quality is poor or the sternum is completely destroyed. The sternal closure systems, consisting of plates, screws or rib clips and titanium bars, have been recently introduced to treat the complicated sternal dehiscence. We describe for the first time the use of the Strasbourg Thoracic Osteosyntheses System (STRATOS) and the greater omentum, to treat a complicated sternal dehiscence, causing chest pain and respiratory failure. PMID- 20584310 TI - Role of thioredoxin reductase 1 and thioredoxin interacting protein in prognosis of breast cancer. AB - INTRODUCTION: The purpose of this work was to study the prognostic influence in breast cancer of thioredoxin reductase 1 (TXNRD1) and thioredoxin interacting protein (TXNIP), key players in oxidative stress control that are currently evaluated as possible therapeutic targets. METHODS: Analysis of the association of TXNRD1 and TXNIP RNA expression with the metastasis-free interval (MFI) was performed in 788 patients with node-negative breast cancer, consisting of three individual cohorts (Mainz, Rotterdam and Transbig). Correlation with metagenes and conventional clinical parameters (age, pT stage, grading, hormone and ERBB2 status) was explored. MCF-7 cells with a doxycycline-inducible expression of an oncogenic ERBB2 were used to investigate the influence of ERBB2 on TXNRD1 and TXNIP transcription. RESULTS: TXNRD1 was associated with worse MFI in the combined cohort (hazard ratio = 1.955; P < 0.001) as well as in all three individual cohorts. In contrast, TXNIP was associated with better prognosis (hazard ratio = 0.642; P < 0.001) and similar results were obtained in all three subcohorts. Interestingly, patients with ERBB2-status-positive tumors expressed higher levels of TXNRD1. Induction of ERBB2 in MCF-7 cells caused not only an immediate increase in TXNRD1 but also a strong decrease in TXNIP. A subsequent upregulation of TXNIP as cells undergo senescence was accompanied by a strong increase in levels of reactive oxygen species. CONCLUSIONS: TXNRD1 and TXNIP are associated with prognosis in breast cancer, and ERBB2 seems to be one of the factors shifting balances of both factors of the redox control system in a prognostic unfavorable manner. PMID- 20584312 TI - 8q24 sequence variants in relation to prostate cancer risk among men of African descent: a case-control study. AB - BACKGROUND: Human chromosome 8q24 has been implicated in prostate tumorigenesis. METHODS: Consequently, we evaluated seven 8q24 sequence variants relative to prostate cancer (PCA) in a case-control study involving men of African descent. Genetic alterations were detected in germ-line DNA from 195 incident PCA cases and 531 controls using TaqMan polymerase chain reaction (PCR). RESULTS: Inheritance of the 8q24 rs16901979 T allele corresponded to a 2.5-fold increase in the risk of developing PCA for our test group. These findings were validated using multifactor dimensionality reduction (MDR) and permutation testing (p = 0.038). The remaining 8q24 targets were not significantly related to PCA outcomes. CONCLUSIONS: Although compelling evidence suggests that the 8q24 rs16901979 locus may serve as an effective PCA predictor, our findings require additional evaluation in larger studies. PMID- 20584313 TI - Analysis of inhibitor of apoptosis protein family expression during mammary gland development. AB - BACKGROUND: Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. Here we examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution. RESULTS: Six out of eight mammalian IAP family members are expressed in the mammary gland. Notably, quantitative PCR and immunoblotting revealed that XIAP, c-IAP1 and c-IAP2 are down-regulated in pregnancy and lactation, and prior to the onset of involution. In cultured mammary epithelial cells (MECs), XIAP levels decreased in response to inhibition of growth factor signalling. Maintaining XIAP levels in MECs by expressing exogenous XIAP protected them from all apoptotic stimuli tested. CONCLUSIONS: These data suggest that the developmental regulation of IAP expression in vivo contributes to naturally occurring programmes of cell death. PMID- 20584314 TI - Herpes simplex virus induces neural oxidative damage via microglial cell Toll like receptor-2. AB - BACKGROUND: Using a murine model of herpes simplex virus (HSV)-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2)-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS) are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. METHODS: Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from beta actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. RESULTS: Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. CONCLUSIONS: These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection. PMID- 20584315 TI - Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. AB - BACKGROUND: The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated. METHODS: Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 x 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure. RESULTS: The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01). CONCLUSIONS: ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS. PMID- 20584317 TI - Tubulohelical membrane arrays: From the initial observation to the elucidation of nanophysical properties and cellular function. AB - Lipids undergo self-assembly to form ordered nonlamellar, nanoperiodic arrays both in vitro and in vivo. While engineering of such membrane arrays for technical devices is envisaged, we know little about their cellular function. Do they represent building blocks of an inherent cellular nanotechnology? Prospects for answering this question could be improved if the nanophysical properties of the membrane arrays could be studied in the context of specific cellular functions. Therefore, we draw attention to exceptional complex membrane arrays found in the renal epithelial cell line PtK2 that could provide perfect conditions for both biophysical and cell functional studies. The so-called tubulohelical membrane arrays (TUHMAs) combine nanoperiodicity of lipid membranes with that of helix-like proteinaceous core structures. Strikingly, they show several characteristics of dynamic, microtubule-associated single organelles. Our initial data indicate that TUHMA formation occurs in the depth of the cytoplasm under participation of cytoplasmic nucleoporins. Once matured, they may fuse with the nuclear membrane in polarized positions, either perpendicularly or in parallel to the nucleus. As a starting point for the initiation of functional studies we found a connection between TUHMAs and primary cilia, indicated by immunolabeling patterns of detyrosynated tubulin and cytoplasmic nucleoporins. We discuss these observations in the context of the ciliary cycle and of the specific requirement of ciliated renal epithelial cells for oriented cell division. Finally, we raise the question of whether putative nanooptical properties of TUHMAs could serve for communicating orientation between dividing cells.MCS codes: 92C37, 92C05, 92C50. PMID- 20584318 TI - Patient with pontine warning syndrome and bilateral posterior internuclear ophthalmoplegia: case report. AB - BACKGROUND: Capsular warning syndrome was first described in 1993, featured with repetitive episodes of motor and/or sensory dysfunction without cortical signs. Recently, it has been demonstrated that clinically typical capsular warning syndrome can be associated with pontine infarct and the term oepontine warning syndrome was coined. CASE PRESENTATION: A 54-year-old woman with a history of hypertension was seen with profound left-sided hemiplegia. She had had 3 episodes of left-sided weakness before complete hemiplegia. Her speech was slurred. Left central facial palsy and hemiglossoplegia were presented. Her left plantar response was extensor and bilateral posterior internuclear ophthalmoplegia was seen on neurologic examination. Biochemical tests revealed hyperglycemia and dyslipidemia on the next day. MRI demonstrated an acute right paramedian pontine infarct. The patient was commenced on oral clopidogrel, atorvastatin and acarbose. After 23 days of hospitalization, she was discharged with severe left hemiplegia. CONCLUSIONS: 1) Pontine warning syndrome may be underestimated and understudied. 2) Posterior internuclear ophthalmoplegia is a rare clinical sign in cerebrovascular diseases, while it can help to locate a brainstem lesion rather than an internal capsular one. 3) Blood pressure lowering administration may be improper for patients with pontine warning syndrome. PMID- 20584316 TI - Comparison of the chloroplast peroxidase system in the chlorophyte Chlamydomonas reinhardtii, the bryophyte Physcomitrella patens, the lycophyte Selaginella moellendorffii and the seed plant Arabidopsis thaliana. AB - BACKGROUND: Oxygenic photosynthesis is accompanied by the formation of reactive oxygen species (ROS), which damage proteins, lipids, DNA and finally limit plant yield. The enzymes of the chloroplast antioxidant system are exclusively nuclear encoded. During evolution, plastid and mitochondrial genes were post endosymbiotically transferred to the nucleus, adapted for eukaryotic gene expression and post-translational protein targeting and supplemented with genes of eukaryotic origin. RESULTS: Here, the genomes of the green alga Chlamydomonas reinhardtii, the moss Physcomitrella patens, the lycophyte Selaginella moellendorffii and the seed plant Arabidopsis thaliana were screened for ORFs encoding chloroplast peroxidases. The identified genes were compared for their amino acid sequence similarities and gene structures. Stromal and thylakoid-bound ascorbate peroxidases (APx) share common splice sites demonstrating that they evolved from a common ancestral gene. In contrast to most cormophytes, our results predict that chloroplast APx activity is restricted to the stroma in Chlamydomonas and to thylakoids in Physcomitrella. The moss gene is of retrotransposonal origin.The exon-intron-structures of 2CP genes differ between chlorophytes and streptophytes indicating an independent evolution. According to amino acid sequence characteristics only the A-isoform of Chlamydomonas 2CP may be functionally equivalent to streptophyte 2CP, while the weakly expressed B- and C-isoforms show chlorophyte specific surfaces and amino acid sequence characteristics. The amino acid sequences of chloroplast PrxII are widely conserved between the investigated species. In the analyzed streptophytes, the genes are unspliced, but accumulated four introns in Chlamydomonas. A conserved splice site indicates also a common origin of chlorobiont PrxQ.The similarity of splice sites also demonstrates that streptophyte glutathione peroxidases (GPx) are of common origin. Besides a less related cysteine-type GPx, Chlamydomonas encodes two selenocysteine-type GPx. The latter were lost prior or during streptophyte evolution. CONCLUSION: Throughout plant evolution, there was a strong selective pressure on maintaining the activity of all three investigated types of peroxidases in chloroplasts. APx evolved from a gene, which dates back to times before differentiation of chlorobionts into chlorophytes and streptophytes, while Prx and presumably also GPx gene patterns may have evolved independently in the streptophyte and chlorophyte branches. PMID- 20584319 TI - Elevated MED28 expression predicts poor outcome in women with breast cancer. AB - BACKGROUND: MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression. METHODS: Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed. RESULTS: MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death. CONCLUSIONS: We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer. PMID- 20584320 TI - Primary breast lymphomas: a multicentric experience. AB - BACKGROUND: The Primary Breast Lymphomas (PBL) represent 0,38-0,70% of all non Hodgkin lymphomas (NHL), 1,7-2,2% of all extranodal NHL and only 0,04-0,5% of all breast cancer. Most frequent PBLs are the diffuse large B cell lymphomas; in any case-reports MALT lymphomas lack or are a rare occurrence. Their incidence is growing. From 1880 (first breast resection for "lymphadenoid sarcoma" carried out by Gross) to the recent past the gold standard treatment for such diseases was surgery. At present such role has lost some of its importance, and it is matter of debate. METHODS: Twenty-three women affected by PBL underwent surgery. Average age was 63 years (range: 39-83). Seven suffered of hypothyroidism secondary to autoimmune thyroiditis. Fourteen patients underwent mastectomy, nine patients received quadrantectomy (average neoplasm diameter: 1.85 cm, range: 1.1-2.6 cm). In 10 cases axillary dissection was carried out. Pathologic examination revealed 16 diffuse large B cell lymphomas and 7 MALT lymphomas. RESULTS: Seven patients in the mastectomy group had a recurrence (50%), and all of them with diffuse large B cell lymphomas at stage II. Two of these had not received chemotherapy. No patient undergoing quadrantectomy had recurrence. In the mastectomy group disease free survival (DFS) at 5 and 10 years was 57 and 50%. Overall survival (OS) at 5 and 10 years was 71.4% and 57.1% respectively. All recurrences were systemic. DFS and OS at 5 and 10 years was 100% in the quadrantectomy group. In the patients with recurrence mortality was 85.7%. For stage IE DFS and OS at 5 and 10 years were 100%. For stage II DFS at 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62.5% respectively. For MALT lymphomas DFS and OS at 5 and 10 years were 100%. For diffuse large B cell lymphomas DFS at 5 and 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62,5% respectively. CONCLUSIONS: The role of surgery in this disease should be limited to get a definitive diagnosis while for the staging and the treatment CT scan and chemo/radiotherapy are respectively mandatory. MALT PBLs have a definitely better prognosis compared to large B cell lymphomas. The surgical treatment must always be oncologically radical (R0); mastectomy must not be carried out as a rule, but only when tissue sparing procedures are not feasible. Axillary dissection must always be performed for staging purposes, so avoiding the risk of under-staging II or IE, due to the possibility of clinically silent axillary node involvement. PMID- 20584321 TI - An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer. AB - BACKGROUND: Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. METHODS: We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. RESULTS: An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. CONCLUSIONS: This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID- 20584322 TI - Pathway analysis comparison using Crohn's disease genome wide association studies. AB - BACKGROUND: The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. METHODS: We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. RESULTS: Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. CONCLUSIONS: Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight. PMID- 20584323 TI - ScreenMill: a freely available software suite for growth measurement, analysis and visualization of high-throughput screen data. AB - BACKGROUND: Many high-throughput genomic experiments, such as Synthetic Genetic Array and yeast two-hybrid, use colony growth on solid media as a screen metric. These experiments routinely generate over 100,000 data points, making data analysis a time consuming and painstaking process. Here we describe ScreenMill, a new software suite that automates image analysis and simplifies data review and analysis for high-throughput biological experiments. RESULTS: The ScreenMill, software suite includes three software tools or "engines": an open source Colony Measurement Engine (CM Engine) to quantitate colony growth data from plate images, a web-based Data Review Engine (DR Engine) to validate and analyze quantitative screen data, and a web-based Statistics Visualization Engine (SV Engine) to visualize screen data with statistical information overlaid. The methods and software described here can be applied to any screen in which growth is measured by colony size. In addition, the DR Engine and SV Engine can be used to visualize and analyze other types of quantitative high-throughput data. CONCLUSIONS: ScreenMill automates quantification, analysis and visualization of high-throughput screen data. The algorithms implemented in ScreenMill are transparent allowing users to be confident about the results ScreenMill produces. Taken together, the tools of ScreenMill offer biologists a simple and flexible way of analyzing their data, without requiring programming skills. PMID- 20584324 TI - Knowledge of human papillomavirus infection and its prevention among adolescents and parents in the greater Milan area, Northern Italy. AB - BACKGROUND: In order to be widely accepted by users, the implementation of a new health intervention requires them to be adequately informed about its clinical importance, benefits and risks. The aim of this study was to provide data on the knowledge of Italian adolescents and parents concerning human papillomavirus (HPV) infection and its prevention in order to allow the development of adequate training programmes. METHODS: Between 2 May and 15 June 2008, we made a cross sectional survey of 863 high school students and 2,331 parents of middle and high school students using two anonymously completed questionnaires covering the knowledge of HPV infection and related diseases, and attitudes to vaccinations. The approached schools were a convenience sample of the schools of the greater Milan area, Northern Italy. RESULTS: More mothers than fathers were aware that HPV infection could concern their children (58% vs 53%; p = 0.004) and were favourable towards vaccinating their children against HPV (68% vs 65%; p = 0.03); among the students, more females than males were aware that HPV infection could concern themselves (45% vs 26%; p < 0.001) and would undergo vaccination against HPV (68% vs 40%; p < 0.001). The parents' propensity to vaccinate their children against HPV was significantly associated with professing the Catholic religion (odds ratio - OR = 0.61, 95% confidence interval - CI 0.46-0.82, being atheist), the gender of the offspring (OR = 1.88, 95% CI 1.53-2.30, having at least one daughter), a propensity to vaccinations in general (OR = 23.1, 95% CI 13.7-38.8), a knowledge that HPV vaccine is aimed at preventing cervical cancer (OR = 2.31, 95% CI 1.69-3.16), and an awareness that HPV could affect their own children (OR = 3.52, 95% CI 2.89-4.29). The students who were aware that HPV infection could affect themselves were more in favour of to HPV vaccination, regardless of whether they were male (OR = 5.73, 95% CI 2.85-11.5) or female (OR = 2.39, 95% CI 1.66-3.46). CONCLUSIONS: Both students and parents seem to underestimate the likelihood of HPV infection, and this is associated with a lower propensity for vaccination. This is an important indication for future training programmes concerning HPV prevention designed to increase the acceptance of HPV vaccine in families. PMID- 20584325 TI - Angiography and embolisation for solid abdominal organ injury in adults - a current perspective. AB - Over the past twenty years there has been a shift towards non-operative management (NOM) for haemodynamically stable patients with abdominal trauma. Embolisation can achieve haemostasis and salvage organs without the morbidity of surgery, and the development and refinement of embolisation techniques has widened the indications for NOM in the management of solid organ injury. Advances in computed tomography (CT) technology allow faster scanning times with improved image quality. These improvements mean that whilst surgery is still usually recommended for patients with penetrating injuries, multiple bleeding sites or haemodynamic instability, the indications for NOM are expanding.We present a current perspective on angiography and embolisation in adults with blunt and penetrating abdominal trauma with illustrative examples from our practice including technical advice. PMID- 20584326 TI - Methicillin Resistant Staphylococcus Aureus Infection as a causative agent of fistula formation following total laryngectomy for advanced head & neck cancer. AB - AIMS: The purpose of this paper was to investigate the impact of Methicillin Resistant Staphylococcus Aureus (MRSA) infection in the aetiology of pharyngo cutaneous fistula (PCF) formation following total laryngectomy for advanced laryngeal cancer. METHODS: This was a retrospective uncontrolled case study series of 31 consecutive patients based in a single institution tertiary referral head and neck oncology centre. RESULTS: Pharyngo-cutaneous fistulas (PCF) following total laryngectomy occurred in 10 (32%) patients. MRSA was identified in 80% of patients with a PCF compared to 9% of patients that did not develop a fistula (p = 0.0001255 Fisher exact test). MRSA infection (p = 0.00012) and previous radiotherapy (p = 0.00025) were the only significant factors found to be important in fistula formation on multivariate analysis. Post-operative infections such as cellulitis, chest infection and carotid fistula were also associated with MRSA infections. CONCLUSION: MRSA infection following total laryngectomy for laryngeal cancer can lead to potential serious complications such as PCF. Patients who underwent total laryngectomy following radiotherapy failure are at a higher risk of acquiring MRSA. PMID- 20584327 TI - Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis. AB - BACKGROUND: The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. METHODS: Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. RESULTS: Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). CONCLUSION: Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology. PMID- 20584329 TI - Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature. AB - BACKGROUND: In vivo studies demonstrate that the Prox1 transcription factor plays a critical role in the development of the early lymphatic system. Upon Prox1 expression, early lymphatic endothelial cells differentiate from the cardinal vein and begin to express lymphatic markers such as VEGFR-3, LYVE-1 and Podoplanin. Subsequent in vitro studies have found that differentiated vascular endothelial cells can be reprogrammed by Prox1 to express a lymphatic gene profile, suggesting that Prox1 can initiate the expression of a unique gene signature during lymphangiogenesis. While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo. RESULTS: Overexpression of Prox1 in vascular endothelial cells during embryonic development results in the reprogramming of genes to that of a more lymphatic signature. Consequent to this overexpression, embryos suffer from gross edema that results in embryonic lethality at E13.5. Furthermore, hemorrhaging and anemia is apparent along with clear defects in lymph sac development. Alterations in junctional proteins resulting in an increase in vascular permeability upon Prox1 overexpression may contribute to the complications found during embryonic development. CONCLUSION: We present a novel mouse model that addresses the importance of Prox1 in early embryonic lymphangiogenesis. It is clear that there needs to be a measured pattern of expression of Prox1 during embryonic development. Furthermore, Prox1 reprograms vascular endothelial cells in vivo by creating a molecular signature to that of a lymphatic endothelial cell. PMID- 20584328 TI - Estimating enrichment of repetitive elements from high-throughput sequence data. AB - We describe computational methods for analysis of repetitive elements from short read sequencing data, and apply them to study histone modifications associated with the repetitive elements in human and mouse cells. Our results demonstrate that while accurate enrichment estimates can be obtained for individual repeat types and small sets of repeat instances, there are distinct combinatorial patterns of chromatin marks associated with major annotated repeat families, including H3K27me3/H3K9me3 differences among the endogenous retroviral element classes. PMID- 20584330 TI - Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD). AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver diseases, ranging from pure steatosis to nonalcoholic steatohepatitis (NASH), and eventually to liver cirrhosis with its complications. Identifying advanced fibrosis in patients is crucial to evaluating prognosis and possible therapeutic intervention. A novel, simple, and highly accurate scoring system called BARD, which identifies patients with NAFLD and without significant fibrosis, has been recently introduced and validated in North America..The aim of this study is to validate the BARD scoring system in a Polish cohort with NAFLD. METHODS: A group of 104 Caucasians with biopsy-proven NAFLD were included in this study. Fibrosis in liver biopsies was evaluated according to the Histological Scoring System for Nonalcoholic Fatty Liver Disease. The BARD scoring system was assessed according to Harrison et al.: BMI > or = 28 = 1 point, AST/ALT ratio (AAR) > or = 0.8 = 2 points, type 2 diabetes mellitus = 1 point. RESULTS: Age over 50 and AAR over 0.8 showed, respectively, a moderate and strong association with advanced fibrosis. A BARD score of 2-4 points was associated with F3 or F4 stages of fibrosis with an odds ratio of 17.333 (95% Cl; 3,639 - 82.558) and negative predictive value of 97%. CONCLUSION: Our results demonstrate that the BARD scoring system has value in the non-invasive diagnosis of advanced fibrosis in NAFLD patients. The vast majority of patients with NAFLD would avoid liver biopsy if BARD was broadly introduced into the clinic. PMID- 20584331 TI - Nonparametric methods for the analysis of single-color pathogen microarrays. AB - BACKGROUND: The analysis of oligonucleotide microarray data in pathogen surveillance and discovery is a challenging task. Target template concentration, nucleic acid integrity, and host nucleic acid composition can each have a profound effect on signal distribution. Exploratory analysis of fluorescent signal distribution in clinical samples has revealed deviations from normality, suggesting that distribution-free approaches should be applied. RESULTS: Positive predictive value and false positive rates were examined to assess the utility of three well-established nonparametric methods for the analysis of viral array hybridization data: (1) Mann-Whitney U, (2) the Spearman correlation coefficient and (3) the chi-square test. Of the three tests, the chi-square proved most useful. CONCLUSIONS: The acceptance of microarray use for routine clinical diagnostics will require that the technology be accompanied by simple yet reliable analytic methods. We report that our implementation of the chi-square test yielded a combination of low false positive rates and a high degree of predictive accuracy. PMID- 20584332 TI - Identifying structures, processes, resources and needs of research ethics committees in Egypt. AB - BACKGROUND: Concerns have been expressed regarding the adequacy of ethics review systems in developing countries. Limited data are available regarding the structural and functional status of Research Ethics Committees (RECs) in the Middle East. The purpose of this study was to survey the existing RECs in Egypt to better understand their functioning status, perceived resource needs, and challenges. METHODS: We distributed a self-administered survey tool to Egyptian RECs to collect information on the following domains: general characteristics of the REC, membership composition, ethics training, workload, process of ethics review, perceived challenges to effective functioning, and financial and material resources. We used basic descriptive statistics to evaluate the quantitative data. RESULTS: We obtained responses from 67% (12/18) of the identified RECs. Most RECs (10/12) have standard operating procedures and many (7/12) have established policies to manage conflicts of interests. The average membership was 10.3 with a range from 7-19. The predominant member type was physicians (69.5% of all of the REC members) with little lay representation (13.7%). Most RECs met at least once/month and the average number of protocols reviewed per meeting was 3.8 with a range from 1-10. Almost three-quarters of the members from all of the 12 RECs indicated they received some formal training in ethics. Regarding resources, roughly half of the RECs have dedicated capital equipment (e.g., meeting room, computers, office furniture, etc); none of the RECs have a formal operating budget. Perceived challenges included the absence of national research ethics guidelines and national standards for RECs and lack of ongoing training of its members in research ethics. CONCLUSION: Our study documents several areas of strengths and areas for improvements in the operations of Egyptian RECs. Regarding strengths, many of the existing RECs meet frequently, have a majority of members with prior training in research ethics, and have written policies. Regarding areas for improvements, many RECs should strive for a more diverse membership and should receive more financial resources and administrative support personnel. We recommend that RECs include more individuals from the community and develop a continuing educational program for its members. Institutional officials should be aware of the resource capacity needs of their RECs. PMID- 20584333 TI - Experiences of physical activity during pregnancy in Danish nulliparous women with a physically active life before pregnancy. A qualitative study. AB - BACKGROUND: National guidelines recommend that healthy pregnant women take 30 minutes or more of moderate exercise a day. Most women reduce the level of physical activity during pregnancy but only a few studies of women's experiences of physical activity during pregnancy exist. The aim of the present study was to elucidate experiences and views of leisure time physical activity during pregnancy in nulliparous women who were physically active prior to their pregnancy. METHODS: A qualitative study was conducted by means of personal interviews. Nineteen women, all with a moderate pre-pregnancy level of physical activity but with different levels of physical activity during pregnancy, participated in the study. Content analysis was applied. RESULTS: In the analyses of experiences and views of physical activities during pregnancy, four categories and nine sub-categories were developed: Physical activity as a lifestyle (Habit and Desire to continue), Body awareness (Pregnancy-related discomfort, Having a complicated pregnancy and A growing body), Carefulness (Feelings of worry and Balancing worry and sense of security) and Sense of benefit (Feelings of happiness and Physical well-being). CONCLUSION: As other studies have also shown, women find that the discomfort and complications associated with pregnancy, the growing body, and a sense of insecurity with physical activity are barriers to maintaining former levels of physical activity. This study adds a new perspective by describing women's perceptions of these barriers and of overcoming them--thus, when pregnant, the majority of the women do not cease to be physically active but continue to be so. Barriers are overcome by applying one's own experience, looking to role models, mirroring the activities of other pregnant women and following the advice of experts (midwives/physiotherapists). Women then continue to be physically active during pregnancy, most often to a lesser extent or in alternative activities, and derive considerable enjoyment and physical well-being from this. PMID- 20584334 TI - Genetic properties of feed efficiency parameters in meat-type chickens. AB - BACKGROUND: Feed cost constitutes about 70% of the cost of raising broilers, but the efficiency of feed utilization has not kept up the growth potential of today's broilers. Improvement in feed efficiency would reduce the amount of feed required for growth, the production cost and the amount of nitrogenous waste. We studied residual feed intake (RFI) and feed conversion ratio (FCR) over two age periods to delineate their genetic inter-relationships. METHODS: We used an animal model combined with Gibb sampling to estimate genetic parameters in a pedigreed random mating broiler control population. RESULTS: Heritability of RFI and FCR was 0.42-0.45. Thus selection on RFI was expected to improve feed efficiency and subsequently reduce feed intake (FI). Whereas the genetic correlation between RFI and body weight gain (BWG) at days 28-35 was moderately positive, it was negligible at days 35-42. Therefore, the timing of selection for RFI will influence the expected response. Selection for improved RFI at days 28 35 will reduce FI, but also increase growth rate. However, selection for improved RFI at days 35-42 will reduce FI without any significant change in growth rate. The nature of the pleiotropic relationship between RFI and FCR may be dependent on age, and consequently the molecular factors that govern RFI and FCR may also depend on stage of development, or on the nature of resource allocation of FI above maintenance directed towards protein accretion and fat deposition. The insignificant genetic correlation between RFI and BWG at days 35-42 demonstrates the independence of RFI on the level of production, thereby making it possible to study the molecular, physiological and nutrient digestibility mechanisms underlying RFI without the confounding effects of growth. The heritability estimate of FCR was 0.49 and 0.41 for days 28-35 and days 35-42, respectively. CONCLUSION: Selection for FCR will improve efficiency of feed utilization but because of the genetic dependence of FCR and its components, selection based on FCR will reduce FI and increase growth rate. However, the correlated responses in both FI and BWG cannot be predicted accurately because of the inherent problem of FCR being a ratio trait. PMID- 20584335 TI - microRNA evolution in a human transcription factor and microRNA regulatory network. AB - BACKGROUND: microRNAs (miRNAs) are important cellular components. The understanding of their evolution is of critical importance for the understanding of their function. Although some specific evolutionary rules of miRNAs have been revealed, the rules of miRNA evolution in cellular networks remain largely unexplored. According to knowledge from protein-coding genes, the investigations of gene evolution in the context of biological networks often generate valuable observations that cannot be obtained by traditional approaches. RESULTS: Here, we conducted the first systems-level analysis of miRNA evolution in a human transcription factor (TF)-miRNA regulatory network that describes the regulatory relations among TFs, miRNAs, and target genes. We found that the architectural structure of the network provides constraints and functional innovations for miRNA evolution and that miRNAs showed different and even opposite evolutionary patterns from TFs and other protein-coding genes. For example, miRNAs preferentially coevolved with their activators but not with their inhibitors. During transcription, rapidly evolving TFs frequently activated but rarely repressed miRNAs. In addition, conserved miRNAs tended to regulate rapidly evolving targets, and upstream miRNAs evolved more rapidly than downstream miRNAs. CONCLUSIONS: In this study, we performed the first systems level analysis of miRNA evolution. The findings suggest that miRNAs have a unique evolution process and thus may have unique functions and roles in various biological processes and diseases. Additionally, the network presented here is the first TF miRNA regulatory network, which will be a valuable platform of systems biology. PMID- 20584336 TI - A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement. AB - BACKGROUND: The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV), however, possesses several mechanisms to evade complement-mediated lysis (CoML) and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH) through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. PRESENTATION OF THE HYPOTHESIS: Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively) linked to a complement-activating human IgG1 Fc domain ((anti-gp120 x anti-C3d)-Fc), can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. TESTING THE HYPOTHESIS: Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 x anti-C3d)-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of (anti-gp120 x anti-C3d)-Fc lysis of HIV compared to untreated virus. IMPLICATIONS OF THE HYPOTHESIS: The targeted complement activator, (anti-gp120 x anti-C3d)-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells. PMID- 20584337 TI - Recurrent furunculosis as a cause of isolated penile lymphedema: a case report. AB - INTRODUCTION: Isolated lymphedema of the penis is extremely rare: combined involvement of the scrotum and penis is the norm. Furunculosis as a cause is not, to our knowledge, previously reported. We present a case of isolated penile lymphedema that responded to excision of lymphedematous tissue and reconstruction with flaps. CASE PRESENTATION: A 32-year-old Arab man presented with a three-year history of a gradually increasing, painless penile swelling. Our patient's main complaint was non-erectile sexual dysfunction. The swelling was preceded by at least three prior episodes of severe furunculosis at the penile root. He had no other contributory past medical or family history. On examination there was gross penile enlargement, maximally at the mid shaft, associated with thickened skin at the sites of prior furunculosis. The glans and scrotum were normal. Both testes were palpable. Serology for filariasis, and urinary tract ultrasound and computed tomography scan were normal. The clinical diagnosis was lymphedema following recurrent penile furunculosis. At operation the lymphedematous tissues were removed. Closure of the penile shaft was accomplished by bilateral advancement of flaps from both ends of the penis. He resumed normal sexual activity one month after surgery. At 12 months, he had a good cosmetic result, with no signs of recurrence. CONCLUSIONS: Furunculosis at the penile root may result in lymphedema confined to the penile shaft, sparing the scrotum. Excision of abnormal tissue and cover with a skin flap gave excellent cosmetic results, and allowed satisfactory sexual activity. PMID- 20584338 TI - Functional network of glycan-related molecules: glyco-net in glycoconjugate data bank. AB - BACKGROUND: Glycans are involved in a wide range of biological process, and they play an essential role in functions such as cell differentiation, cell adhesion, pathogen-host recognition, toxin-receptor interactions, signal transduction, cancer metastasis, and immune responses. Elucidating pathways related to post translational modifications (PTMs) such as glycosylation are of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids and various biological events are considered extremely valuable and convenient tools for the systematic investigation of PTMs. However, there is no database which dynamically draws functional networks related to glycans. DESCRIPTION: We have created a database called Glyco-Net http://www.glycoconjugate.jp/functions/, with many binary relationships among glycan-related molecules. Using search results, we can dynamically draw figures of the functional relationships among these components with nodes and arrows. A certain molecule or event corresponds to a node in the network figures, and the relationship between the molecule and the event are indicated by arrows. Since all components are treated equally, an arrow is also a node. CONCLUSIONS: In this paper, we describe our new database, Glyco-Net, which is the first database to dynamically show networks of the functional profiles of glycan related molecules. The graphical networks will assist in the understanding of the role of the PTMs. In addition, since various kinds of bio-objects such as genes, proteins, and inhibitors are equally treated in Glyco-Net, we can obtain a large amount of information on the PTMs. PMID- 20584340 TI - A review of the trunk surface metrics used as Scoliosis and other deformities evaluation indices. AB - BACKGROUND: Although scoliosis is characterized by lateral deviation of the spine, a 3D deformation actually is responsible for geometric and morphologic changes in the trunk and rib cage. In a vast related medical literature, one can find quite a few scoliosis evaluation indices, which are based on back surface data and are generally measured along three planes. Regardless the large number of such indices, the literature is lacking a coherent presentation of the underlying metrics, the involved anatomic surface landmarks, the definition of planes and the definition of the related body axes. In addition, the long list of proposed scoliotic indices is rarely presented in cross-reference to each other. This creates a possibility of misunderstandings and sometimes irrational or even wrong use of these indices by the medical society. MATERIALS AND METHODS: It is hoped that the current work contributes in clearing up the issue and gives rise to innovative ideas on how to assess the surface metrics in scoliosis. In particular, this paper presents a thorough study on the scoliosis evaluation indices, proposed by the medical society. RESULTS: More specifically, the referred indices are classified, according to the type of asymmetry they measure, according to the plane they refer to, according to the importance, and relevance or the level of scientific consensus they enjoy. CONCLUSIONS: Surface metrics have very little correlation to Cobb angle measurements. Indices measured on different planes do not correlate to each other. Different indices exhibit quite diverging characteristics in terms of observer-induced errors, accuracy, sensitivity and specificity. Complicated positioning of the patient and ambiguous anatomical landmarks are the major error sources, which cause observer variations. Principles that should be followed when an index is proposed are presented. PMID- 20584339 TI - Small RNAs, DNA methylation and transposable elements in wheat. AB - BACKGROUND: More than 80% of the wheat genome is composed of transposable elements (TEs). Since active TEs can move to different locations and potentially impose a significant mutational load, their expression is suppressed in the genome via small non-coding RNAs (sRNAs). sRNAs guide silencing of TEs at the transcriptional (mainly 24-nt sRNAs) and post-transcriptional (mainly 21-nt sRNAs) levels. In this study, we report the distribution of these two types of sRNAs among the different classes of wheat TEs, the regions targeted within the TEs, and their impact on the methylation patterns of the targeted regions. RESULTS: We constructed an sRNA library from hexaploid wheat and developed a database that included our library and three other publicly available sRNA libraries from wheat. For five completely-sequenced wheat BAC contigs, most perfectly matching sRNAs represented TE sequences, suggesting that a large fraction of the wheat sRNAs originated from TEs. An analysis of all wheat TEs present in the Triticeae Repeat Sequence database showed that sRNA abundance was correlated with the estimated number of TEs within each class. Most of the sRNAs perfectly matching miniature inverted repeat transposable elements (MITEs) belonged to the 21-nt class and were mainly targeted to the terminal inverted repeats (TIRs). In contrast, most of the sRNAs matching class I and class II TEs belonged to the 24-nt class and were mainly targeted to the long terminal repeats (LTRs) in the class I TEs and to the terminal repeats in CACTA transposons. An analysis of the mutation frequency in potentially methylated sites revealed a three-fold increase in TE mutation frequency relative to intron and untranslated genic regions. This increase is consistent with wheat TEs being preferentially methylated, likely by sRNA targeting. CONCLUSIONS: Our study examines the wheat epigenome in relation to known TEs. sRNA-directed transcriptional and post transcriptional silencing plays important roles in the short-term suppression of TEs in the wheat genome, whereas DNA methylation and increased mutation rates may provide a long-term mechanism to inactivate TEs. PMID- 20584341 TI - Predictors of nursing home admission of individuals without a dementia diagnosis before admission - results from the Leipzig Longitudinal Study of the Aged (LEILA 75+). AB - BACKGROUND: In previous decades a substantial number of community-based studies mostly including dementia cases examined predictors of nursing home admission (NHA) among elderly people. However, no one study has analysed predictors of NHA for individuals without developing dementia before NHA. METHODS: Data were derived from the Leipzig Longitudinal Study of the Aged, a population-based study of individuals aged 75 years and older. 1,024 dementia-free older adults were interviewed six times on average every 1.4 years. Socio-demographic, clinical, and psychometric variables were obtained. Kaplan-Meier estimates were used to determine mean time to NHA. Cox proportional hazards regression was used to examine predictors of long-term NHA. RESULTS: Of the overall sample, 7.8 percent of the non-demented elderly (n = 59) were admitted to nursing home (NH) during the study period. The mean time to NHA in the dementia-free sample was 7.6 years. Characteristics associated with a shorter time to NHA were increased age, living alone, functional and cognitive impairment, major depression, stroke, myocardial infarction, a low number of specialist visits and paid home helper use. CONCLUSIONS: Severe physical or psychiatric diseases and living alone have a significant effect on NHA for dementia-free individuals. The findings offer potentialities of secondary prevention to avoid or delay NHA for these elderly individuals. Further investigation of predictors of institutionalization is warranted to advance understanding of the process leading to NHA for this important group. PMID- 20584342 TI - Ventilation inhomogeneity is one criterion among many in multidimensional PEEP titration. PMID- 20584343 TI - Association between the spread of circulating tumor cells and breast cancer subtypes. PMID- 20584345 TI - Managing bone mineral density with oral bisphosphonate therapy in women with breast cancer receiving adjuvant aromatase inhibition. AB - The use of adjuvant aromatase inhibitors is associated with an increased risk of osteoporosis and fractures. The oral bisphosphonate, risedronate--dosed as the US Food and Drug Administration approved for the treatment or prevention of postmenopausal osteoporosis--appears to mitigate bone loss associated with 2 years of adjuvant anastrozole in women with early-stage breast cancer. PMID- 20584344 TI - The contribution of dynamic stromal remodeling during mammary development to breast carcinogenesis. AB - Breast cancer is a heterogeneous disease whose prognosis varies depending upon the developmental stage of the breast tissue at diagnosis. Notably, breast cancers associated with pregnancy exhibit increased rates of metastasis and poorer long-term survival compared to those diagnosed after menopause. However, postmenopausal breast cancers associated with obesity exhibit a more aggressive behavior and confer decreased overall patient survival compared to those diagnosed in non-obese individuals. Since the mammary gland is a dynamic tissue that undergoes significant changes throughout a woman's lifetime, especially during pregnancy and following menopause, we present evidence to support the notion that changes occurring throughout development within the mammary stromal compartment may account for some of the biological differences in breast cancer subtypes and behaviors. PMID- 20584346 TI - Immune status in sepsis: the bug, the site of infection and the severity can make the difference. AB - Studying a large number of patients with sepsis, the Hellenic sepsis study group led by Evangello Giamarellos-Bourboulis emphasizes that the nature of the bacterial infection, its origin (community or nosocomial), its site, and its severity exert different pressures on the immune system. Their study illustrates the heterogeneity of patients with sepsis and points out that numerous key parameters of severe infection influence immune status. PMID- 20584347 TI - Biopsy-proven myocardial sequels in Kawasaki disease with giant coronary aneurysms. AB - BACKGROUND: Although most Kawasaki disease with giant coronary aneurysms is asymptomatic, conventional investigations might not identify previous lesions, or all Kawasaki disease with giant aneurysms at risk of future myocardial lesions. We evaluated the long-term histopathology of the myocardium, especially of intramural small vessels in asymptomatic Kawasaki disease with giant aneurysms. METHOD: The initial study comprised 16 consecutive Kawasaki patients - male-to female ratio was 12:4 - aged from 2 to 12 years, and in the subsequent study, the same patients were aged from 4.9 to 16 years. Endomyocardial biopsies were histopathologically evaluated. Microangiopathies, mitochondrial abnormalities, and loss or disarray of myofibrils were compared by electron microscopy. RESULTS: The incidence of histopathological abnormalities such as degeneration, hypertrophy, and inflammatory cell infiltration was quite high in the initial study, and inflammatory cell infiltration, interstitial fibrosis, and disarray were very noticeable at follow-up biopsies. The area of fibrous tissue was significantly higher in patients administered with intravenous immunoglobulin at follow-up biopsies. Electron microscopy showed microangiopathies including microthrombi within intramural small vessels in some patients at follow-up biopsies. The sites of the coronary aneurysms did not seem to have an impact on the biopsy findings, suggesting that the underlying pathophysiology is related to the original disease process. CONCLUSIONS: Whether the abnormalities were due to direct myocardial injury, chronic ischaemia, repeated small-vessel thrombosis, or other problems associated only with biopsies, is difficult to determine. However, this subgroup had residual abnormal lesions in the myocardium. Follow-up should be more aggressive in this group of patients to identify myocardial damage that could be asymptomatic. PMID- 20584348 TI - Acute viral myocarditis: role of immunosuppression: a prospective randomised study. AB - OBJECTIVE: To conduct a prospective randomised study to show the efficacy of immune suppression with prednisolone, administered at the 3-month duration of acute myocarditis. METHODS: The diagnosis of acute viral myocarditis was made based on echocardiography and serum viral antibodies. The inclusion criterion was acute myocarditis of 3 months duration. In all, 68 of 173 children were available for randomisation into a prednisolone-treated group of 44 and a control group of 24 children. The follow-up period in the prednisolone-treated group was 15.1 plus or minus 9.2 months and 13.6 plus or minus 10.6 months for the control group. RESULTS: Compared with controls, 1 month after randomisation significantly more children in the prednisolone-treated group increased their ejection fraction to more than 40% (p = 0.029). Discrete analysis of change in the ejection fraction from the one at randomisation to one after 1 month of randomisation of greater than 10% and less than 10% or no change between groups showed a significantly greater number with improvement in the prednisolone-treated group (p = 0.019). At the end of the follow-up visits, a significantly larger number of children in the prednisolone-treated group had an ejection fraction of more than 60% compared with the control group (p = 0.049). CONCLUSION: It is concluded that immune suppression with prednisolone, administered at 3 months of the onset of acute myocarditis, is effective in significantly bringing about improvement and cure in persistent left ventricular failure. PMID- 20584349 TI - Asymptomatic rhythm and conduction abnormalities in children with acute rheumatic fever: 24-hour electrocardiography study. AB - Some rhythm and conduction abnormalities can occur in children with acute rheumatic fever. These abnormalities have been defined based on standard electrocardiography; however, the real prevalence of these abnormalities has not been investigated previously by the evaluation of long-term electrocardiographic recordings. In this study, we evaluated the asymptomatic rhythm and conduction abnormalities in children with acute rheumatic fever by evaluating the 24-hour electrocardiography. We evaluated the standard electrocardiography and the 24 hour electrocardiography of 64 children with acute rheumatic fever. On standard electrocardiography, the frequency of the first-degree atrioventricular block was found to be 21.9%. Electrocardiography at 24 hours detected three additional and separate patients with a long PR interval. Mobitz type I block and atypical Wenckebach periodicity were determined in one patient (1.56%) on 24-hour electrocardiography. While accelerated junctional rhythm was detected in three patients on standard electrocardiography, it was present in nine patients according to 24-hour electrocardiography. Premature contractions were present in 1.7% of standard electrocardiography, but in 29.7% of 24-hour electrocardiography. Absence of carditis was found to be related to the presence of accelerated junctional rhythm (p > 0.05), and the presence of carditis was found to be related to the presence of premature contractions (p = 0.000). In conclusion, our results suggest that in children with acute rheumatic fever, the prevalence of rhythm and conduction abnormalities may be much higher than determined on standard electrocardiography. Further studies are needed to clarify whether or not these abnormalities are specific to acute rheumatic fever. PMID- 20584350 TI - Prevalence of consanguineous marriages among Iranian Georgians. AB - Consanguineous marriage--marriage between relatives--has received a great deal of attention as a potential risk factor for many adverse health outcomes. The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Iranian Georgians living in Frydoonshahr (Isfahan province, central Iran). Data on consanguineous marriages were collected using a simple questionnaire. The total number of couples in this study was 646. Consanguineous marriage was classified by the degree of relationship between couples. First cousin marriages (14.2%) were the most common type of consanguineous marriages, followed by second cousin (7.0%), beyond second cousin (1.5%) and first cousin once removed (0.6%). The mean inbreeding coefficient (alpha) was calculated as 0.0104 for the population. The present study shows that the study population, as other Iranian populations, has a high level of consanguinity. PMID- 20584351 TI - Psychosocial correlates of body mass index in four groups of Quebec adults. AB - The objective of the present analysis was to study the associations between body weight psychosocial correlates and body mass index (BMI) among four groups of adults in the Quebec population. Data were taken from the Social Lifestyles and Health 1998 Survey performed by the Institut de la Statistique du Quebec (ISQ). The suggested guidelines of the ISQ were used to estimate the population's proportions and for statistical analysis. The groups studied were 25- to 44- and the 45- to 64-year-old men and women. In all groups, currently trying to lose weight increased the odds of reporting an excess weight. Better perceived eating habits was associated with lower BMI in most groups except in the 25- to 44-year old women, where the trend was not significant. Higher number of physical activities related to transport and cigarette smoking were associated with lower BMI in both men groups. In both women groups, more frequent consumption of alcoholic beverages decreased significantly the odds of reporting excess body weight. A university degree was associated with a lower BMI only in the 25- to 44 year-old men. Regular practise of leisure time physical activity was associated with a lower BMI only in 45- to 64-year-old women. Opposite associations were observed between perceived health and BMI. In the 45- to 64-year-old men, better perceived health increased the odds of reporting an excess weight. Conversely, the odds of reporting excess weight decreased with better health in 25- to 44 year-old women. Many correlates differ between age group and sex. The identification of these factors illustrates the need to adapt obesity-related programmes toward specific sub-groups within the general population. PMID- 20584352 TI - Comparing knowledge and use of health services of migrants from rural and urban areas in Kunming City, China. AB - This paper compares the knowledge and utilization of health services among rural residents, urban residents, rural migrants and urban migrants in a large Chinese city. Data were obtained from a questionnaire survey of 2765 individuals (1951 heads of households and 814 spouses) in Guandu district, Kunming, in 2005. The determinants of their knowledge and utilization of health services were analysed using multivariate logistic regression. First, the migrant population was less likely to know of, or utilize, high-level hospitals and township hospitals than residents. Migrants were more likely to utilize private rather than public services for general health care and delivery care. Second, there was a difference between rural migrants and urban migrants in terms of knowledge and utilization of health services. Rural migrants utilized more low-cost private clinics, but had less knowledge about sources of condoms than urban migrants. Finally, rural residents had more knowledge and utilization of township hospitals than urban residents. This latter group were more likely to utilize high-level hospitals. Migrants' access to health care in urban China is understood better using a dual rural-urban and migrant-resident analytical framework. Rural migrants are the most disadvantaged in their access to urban health care. Further reform of the registered residence system and urban public financing system is recommended. Better information on services and their utilization should be provided to migrants and residents. PMID- 20584353 TI - Building sites for science. PMID- 20584354 TI - The cost-effectiveness of the SPHERE intervention for the secondary prevention of coronary heart disease. AB - OBJECTIVES: The Secondary Prevention of Heart disEase in geneRal practicE (SPHERE) trial has recently reported. This study examines the cost-effectiveness of the SPHERE intervention in both healthcare systems on the island of Ireland. METHODS: Incremental cost-effectiveness analysis. A probabilistic model was developed to combine within-trial and beyond-trial impacts of treatment to estimate the lifetime costs and benefits of two secondary prevention strategies: Intervention - tailored practice and patient care plans; and Control - standardized usual care. RESULTS: The intervention strategy resulted in mean cost savings per patient of euro512.77 (95 percent confidence interval [CI], -1086.46 91.98) and an increase in mean quality-adjusted life-years (QALYs) per patient of 0.0051 (95 percent CI, -0.0101-0.0200), when compared with the control strategy. The probability of the intervention being cost-effective was 94 percent if decision makers are willing to pay euro45,000 per additional QALY. CONCLUSIONS: Decision makers in both settings must determine whether the level of evidence presented is sufficient to justify the adoption of the SPHERE intervention in clinical practice. PMID- 20584355 TI - Low-molecular-weight heparins: pharmacoeconomic decision modeling based on meta analysis data. AB - OBJECTIVES: The aim of this study was to compare efficacy, safety, and consumption of low-molecular-weight heparins with unfractionated heparin, and to develop a pharmacoeconomic decision model based on meta-analysis data. METHODS: Review and meta-analysis were performed of published randomized control trials directly comparing the safety and efficacy of low-molecular-weight heparins (LMWHs)-that is, nadroparin, enoxaparin, and dalteparin-and unfractionated heparin (UFH) was performed by two reviewers using inclusion/exclusion criteria based on the research objectives. The value of fixed effects and random effects odds ratio (95 percent confidence interval) was calculated for each trial for the composite end point. Subsequently, a pharmacoeconomic decision modeling based on reference pricing methodology was implemented. RESULTS: In comparison to UFH, all LMWHs have independently demonstrated greater safety and effectiveness. None of the LMWHs demonstrated a significant superiority over each other; therefore, the group of LMWHs was interchangeable and suitable for cost minimization analysis and reference price implementation. Being the least expensive option, dalteparin single DDD price was set as the reference. Introduction of reference pricing for LMWHs would decrease the total expenditure on LMWHs of approximately 30 percent and would result in total savings of 1.830-2.070 thousand LTL in the country of Lithuania (approximately 0.8 million USD) per year. CONCLUSIONS: The meta analysis results of LMWHs could be used to support a policy on reference-based pricing and pharmacoeconomic decision modeling in healthcare institutions, which would allow a decrease in healthcare expenditures. PMID- 20584356 TI - Quality-adjusted life expectancy benefits of laparoscopic bariatric surgery: a United States perspective. AB - OBJECTIVES: The method of choice for bariatric surgery remains controversial. The aim of this study was to compare the outcome of laparoscopic Roux-en-Y gastric bypass (L-RYGB) versus laparoscopic adjustable gastric banding (LAGB) using quality-adjusted life-years (QALYs). METHODS: We developed a Markov model of the quality of life and survival of L-RYGB and LAGB in obese patients. Using census data, we estimated the probability of dying and quality of life for each year of each cohort. RESULTS: For all cohorts, L-RYGB offers the highest advantage in QALYs compared with gastric banding. The youngest cohort showed the greatest discrepancy between the two surgical methods, with 7.8, 6.4, and 4.7 QALYs gained with L-RYGB over LAGB for the age groups 35, 45, and 55, respectively. Those with the highest presurgical body mass index (BMI) acquired the most advantage with L RYGB, with 2.8, 6.4, and 9.6 QALYs gained with L-RYGB over LAGB for the BMI groups 40, 50, and 60. Males had a slightly higher advantage with L-RYGB, with 6.5 QALYs gained with L-RYGB over LAGB compared with 6.0 QALYs for females. CONCLUSIONS: For the cohorts studied, L-RYGB is the preferred surgical treatment for obesity if the sole metric is QALYs. The young and extremely obese are core groups who will gain the most QALYs following L-RYGB. PMID- 20584357 TI - Extending influenza vaccination to individuals aged 50-64: a budget impact analysis. AB - OBJECTIVES: Influenza (vernacular name, flu) is a viral infection that causes a high consumption of resources. Several studies have been carried out to provide an economic evaluation of the vaccination programs against influenza. Nevertheless, there is still a lack of evidence about the dynamic effects resulting from the reduction of the transmission power. This study considers the impact on contagiousness of alternative strategies against influenza in people aged 50-64 in Italy, France, Germany, and Spain. METHODS: By using the Influsim 2.0 dynamic model, we have determined the social benefits of different coverage levels in every country compared with the ones currently recommended. We have subsequently performed a Budget Impact Analysis to determine whether the currently recommended coverage results from an optimal budget allocation. A probabilistic sensitivity analysis was also conducted. RESULTS: We found that in Germany, the optimal coverage level is 38.5 percent, in France 32.4 percent, in Italy 32.75 percent, and 28.3 percent in Spain. By extending the coverage level, social saving tends to increase up to 100 percent for France and Italy and up to 80 percent for Germany and Spain. CONCLUSIONS: Decision makers should allocate the budget for vaccination against influenza consistently with the estimation of the optimal coverage level and with the dynamic effects resulting from the reduction of the transmission power. PMID- 20584358 TI - Integrating local data into hospital-based healthcare technology assessment: two case studies. AB - OBJECTIVES: Health technology assessment (HTA) programs influence practice on a broad scale through reimbursement decisions or national guidelines. Hospital based HTA programs inform clinical decisions at the local level. Typically, they do this by adapting general HTA to their local setting, or by creating new HTA. However, unlike payer-based HTA organizations, hospital-based HTA organizations can also integrate local data into their reports. METHODS: We describe two examples of local data integrated into hospital-based HTA. In the first, qualitative data were used to select a new cardiac catheterization lab. In the second, quantitative data was used to inform a decision on whether to continue telemedicine services to critical care units. Local evidence sources included equipment service records, and interviews with physicians, technicians, and administrative staff in the first example, and the hospital's administrative and claims databases in the second example. RESULTS: In each case, there was little evidence from the peer-reviewed literature that could be applied to the decision. In the first example, staffing patterns and local preferences had considerable bearing on technology choices. In the second example, local outcomes data from administrative records were decisive. CONCLUSIONS: Hospital-based HTA using local data can fill gaps in the published evidence, and also improve the generalizability of evidence to the local setting. To take advantage of local evidence, health systems should encourage the development of hospital-based HTA centers, seek out local preference data, and maintain databases of patient outcomes and utilization of services. PMID- 20584359 TI - Economic evaluation, human immunodeficiency virus infection and screening: a review and critical appraisal of economic studies. AB - OBJECTIVES: The aim of this study was to review, systematically and critically, evidence used to derive estimates of cost-effectiveness of human immunodeficiency virus (HIV) screening. METHODS: A systematic review was conducted. Searched were three main electronic bibliographic databases from 1993 to 2008 using key words including HIV, mass screening, HAART, economic evaluation, cost-effectiveness analysis, modeling. We included studies of sexually transmitted HIV infection in both sexes, including studies comparing diagnostic testing protocols and partner notification. Outcomes included were cases of HIV infection detected, deterioration to the AIDS state, secondary transmission of HIV, the quality adjusted life-years/survival, costs, and cost-effectiveness of HIV screening. RESULTS: Eighty-four papers were identified; ten of which were formal economic evaluations, one cost study, three effectiveness studies, and three systematic reviews of HIV prevention programs. The predominant assertion was that HIV screening is cost-effective; methodological problems, such as the preponderance of static models which are inappropriate for infectious diseases, varying perspectives from which the studies were analyzed, and arbitrary threshold incremental cost-effectiveness ratio levels, limited the validity of these findings, and their usefulness in informing health policy decisions. CONCLUSIONS: The majority of published economic evaluations are based on inappropriate static models. This flaw renders the results of these studies as inconclusive and the purported cost-effectiveness of HIV screening debatable. The results of this review could form a basis for consideration of further research and analysis by health economists into the cost-effectiveness of HIV screening. PMID- 20584360 TI - Health technology assessment to optimize health technology utilization: using implementation initiatives and monitoring processes. AB - BACKGROUND: The way in which a health technology is used in any particular health system depends on the decisions and actions of a variety of stakeholders, the local culture, and context. In 2009, the HTAi Policy Forum considered how health technology assessment (HTA) could be improved to optimize the use of technologies (in terms of uptake, change in use, or disinvestment) in such complex systems. METHODS: In scoping, it was agreed to focus on initiatives to implement evidence based guidance and monitoring activities. A review identified systematic reviews of implementation initiatives and monitoring activities. A two-day deliberative workshop was held to discuss key papers, members' experiences, and collectively address key questions. This consensus paper was developed by email and finalized at a postworkshop meeting. RESULTS: Evidence suggests that the impact and use of HTA could be increased by ensuring timely delivery of relevant reports to clearly determined policy receptor (decision-making) points. To achieve this, the breadth of assessment, implementation initiatives such as incentives and targeted, intelligent dissemination of HTA result, needs to be considered. HTA stakeholders undertake a variety of monitoring activities, which could inform optimal use of a technology. However, the quality of these data varies and is often not submitted to an HTA. CONCLUSIONS: Monitoring data should be sufficiently robust so that they can be used in HTA to inform optimal use of technology. Evidence-based implementation initiatives should be developed for HTA, to better inform decision makers at all levels in a health system about the optimal use of technology. PMID- 20584361 TI - The usefulness of NICE guidance in practice: different perspectives of managers, clinicians, and patients. AB - OBJECTIVES: The UK National Institute for Health and Clinical Excellence (NICE) has been widely hailed as an international leader in health technology assessment. The objectives of its guidance are to ensure uniformity in healthcare provision, and promote a systematic and accountable way to allocate resources. However, research relating to the implementation of guidance is limited, and little is known about how it influences decision making at the consultation level or how useful it is to individual patients. METHODS: In-depth interviews were undertaken with professionals involved in healthcare provision at the community level, and with clinical professionals and patients providing or receiving care for morbid obesity and breast cancer (n = 52). RESULTS: Although NICE guidance was generally well-regarded, in practice it was of more importance and usefulness to managerial than clinical professionals. Clinicians used a patchy approach to implementation depending on whether recommendations accorded with their personal interpretation of the evidence available, and whether funding was available locally. Many patients had not heard of NICE, and clinical professionals did not alert them to its existence. Even where patients knew about relevant guidance, they were rarely able to use it to assert their right to treatment. CONCLUSIONS: These findings challenge the perception that NICE guidance results in consistent and accountable decision making, and the limited accessibility and usefulness of guidance to patients suggests more information and support is needed at the point of provision if these objectives are to be achieved. PMID- 20584362 TI - Are adverse effects incorporated in economic models? A survey of current practice. AB - BACKGROUND: Clearly the benefits of a treatment must not be outweighed by the adverse effects. If researchers fail to incorporate adverse effects adequately in models, this could limit the validity of the results obtained. In the worst case, interventions that are cost-effective may be shown not to be. The aim of this research was to review current practice when incorporating adverse effects in economic models. METHODS: A survey of HTA reports commissioned by the National Institute for Health Research (NIHR) Health Technology Assessment programme, published between 2004 and 2007 was conducted. All reports which investigated the clinical and cost-effectiveness of a health technology using a systematic review and an economic model framework were included. RESULTS: A total of eighty reports met the inclusion criteria. Of the models including adverse effects (43/80), 67 percent used a clinical adverse effects parameter, 79 percent a cost of adverse effects parameter, 86 percent used one of these, and 60 percent used both. Of the thirty-seven models that did not include adverse effects, eighteen justified this omission, most commonly lack of data; nineteen appeared to make no explicit consideration of adverse effects in the model. CONCLUSIONS: In many cases, poor reporting made it difficult to ascertain if there had been any consideration of adverse effects. We suggest that the findings of this survey support a call for much clearer and explicit reporting of adverse effects, or their exclusion, in decision models and for explicit recognition in future guidelines that "all relevant outcomes" should include some consideration of adverse events. PMID- 20584363 TI - Modeling in pharmacoeconomic studies: funding sources and outcomes. AB - OBJECTIVES: The prime objective of this study was to investigate whether sponsorship by the pharmaceutical industry affected the results of full economic evaluations (FEE) based on modeling. In particular, we focused on the flourishing literature based on Markov models, by far the most widely exploited tool for estimating lifetime costs and benefits. METHODS: We made a literature search of the international database PubMed to find all the studies on pharmacological treatments based on Markov models published in English in the period January 1, 2004 to June 30, 2009. We selected the FEEs focused on single drugs only, specifically cost-effectiveness and cost-utility analyses. Two hundred articles including FEEs based on Markov models were considered eligible. For the analysis, we classified the FEEs into two groups according to whether or not they had financial backing from the pharmaceutical industry. We then assessed the main conclusions, which were classified as (i) "favorable," (ii) "doubtful," and (iii) "unfavorable." RESULTS: Of the 200 articles, 138 (69 percent) were sponsored and 162 (81 percent) reached favorable conclusions. Sponsored studies were much more likely to report favorable conclusions than nonsponsored ones (95 percent and 50 percent, p < .001), the former even omitting unfavorable conclusions. CONCLUSIONS: The review found a substantial share of studies supported by the pharmaceutical industry, almost all concluding in favor of the drug studied, without any unfavorable conclusions at all. These results confirm also in the field of pharmacoeconomic studies that the best way of limiting confounding factors is by clearly distinguishing assessors from manufacturers and marketers of any new technology. PMID- 20584364 TI - Patients' perspectives in health technology assessment: a route to robust evidence and fair deliberation. AB - There is increasing emphasis on providing patient-focused health care and ensuring patient involvement in the design of health services. As health technology assessment (HTA) is meant to be a multidisciplinary, wide-ranging policy analysis that informs decision making, it would be expected that patients' views should be incorporated into the assessment. However, HTA is still driven by collection of quantitative evidence to determine the clinical and cost effectiveness of a health technology. Patients' perspectives about their illness and the technology are rarely included, perhaps because they are seen as anecdotal, biased views. There are two distinct but complementary ways in which HTAs can be strengthened by: (i) gathering robust evidence about the patients' perspectives, and (ii) ensuring effective engagement of patients in the HTA process from scoping, through evidence gathering, assessment of value, development of recommendations and dissemination of findings. Robust evidence eliciting patients' perspectives can be obtained through social science research that is well conducted, critically appraised and carefully reported, either through meta-synthesis of existing studies or new primary research. Engagement with patients can occur at several levels and we propose that HTA should seek to support effective patient participation to create a fair deliberative process. This should allow two-way flow of information, so that the views of patients are obtained in a supportive way and fed into decision-making processes in a transparent manner. PMID- 20584365 TI - Priority setting for health technology assessment at CADTH. AB - OBJECTIVES: The aim of this study was to describe a current practical approach of priority setting of health technology assessment (HTA) research that involves multi-criteria decision analysis and a deliberative process. METHODS: Criteria related to HTA prioritization were identified and grouped through a systematic review and consultation with a selection committee. Criteria were scored through a pair-wise comparison approach. Criteria were pruned based on the average weights obtained from consistent (consistency index < 0.2) responders and consensus. HTA proposals are ranked based on available information and a weighted criteria score. The rank, along with additional contextual information and discussion among committee members, is used to achieve consensus on HTA research priorities. RESULTS: Six of eleven criteria represented > 75 percent of the weight behind committee member decisions to conduct an HTA. These criteria were disease burden, clinical impact, alternatives, budget impact, economic impact, and available evidence. Since May 2006, committees have considered 102 proposals at sixteen biannual in-person advisory committee meetings. These have selected twenty-nine research priorities for the HTA program. CONCLUSIONS: The approach works well and was easy to implement. Feedback from committee members has been positive. This approach may assist HTA and other research agencies in better priority setting by informing the selection of the most important and policy relevant topics in the presence of a wide variety of research proposals. This may in turn lead to efficiently allocating resources available for HTA research. PMID- 20584366 TI - Evaluation criteria to assess the value of identification sources for horizon scanning. AB - OBJECTIVES: The English National Horizon Scanning Centre routinely scans thirty five sources to identify new and emerging health technologies. The aim of the study was to develop and apply evaluation criteria and scores to assess the value of sources, and to identify a cutoff score below which sources would be recommended for removal from routine horizon scanning. Criteria to evaluate each source scanned could result in a more efficient approach in the selection process. METHODS: Evaluation criteria were developed following a review of the literature and discussions with horizon analysts. Proposed criteria were piloted on a random selection of six sources, and then applied to all thirty-five sources. The criteria were assessed using the Analytic Hierarchy Process. RESULTS: Eight criteria were identified as being most relevant for assessing the value of scanning sources. The three most important (primary) criteria were coverage (approximate percentage of relevant information), quality (reliable, accurate, objective), and efficiency (estimated time to identify one potentially significant health technology or other relevant information). Seven sources fell beneath the cutoff score and were recommended for removal from routine scanning. CONCLUSIONS: The criteria were considered useful in the assessment of current sources, and have the potential to be used to assess new ones. These criteria may be useful for other horizon scanning centers to pilot and validate. PMID- 20584367 TI - Capsule endoscopy in Italy: an unbalanced review of the literature. PMID- 20584369 TI - Comorbidity: a network perspective. AB - The pivotal problem of comorbidity research lies in the psychometric foundation it rests on, that is, latent variable theory, in which a mental disorder is viewed as a latent variable that causes a constellation of symptoms. From this perspective, comorbidity is a (bi)directional relationship between multiple latent variables. We argue that such a latent variable perspective encounters serious problems in the study of comorbidity, and offer a radically different conceptualization in terms of a network approach, where comorbidity is hypothesized to arise from direct relations between symptoms of multiple disorders. We propose a method to visualize comorbidity networks and, based on an empirical network for major depression and generalized anxiety, we argue that this approach generates realistic hypotheses about pathways to comorbidity, overlapping symptoms, and diagnostic boundaries, that are not naturally accommodated by latent variable models: Some pathways to comorbidity through the symptom space are more likely than others; those pathways generally have the same direction (i.e., from symptoms of one disorder to symptoms of the other); overlapping symptoms play an important role in comorbidity; and boundaries between diagnostic categories are necessarily fuzzy. PMID- 20584370 TI - Latent variables and the network perspective. AB - We discuss the latent variables construct, particularly in regard to the following: that latent variables are considered as the sole explanatory factor of a disorder; that pragmatic concerns are ignored; and that the relationship of these variables to biological markers is not addressed. Further, we comment on the relationship between bridge symptoms and causality, and discuss the proposal in relationship to other constructs (endophenotypes, connectionist-inspired networks). PMID- 20584371 TI - The rocky road from Axis I to Axis II: extending the network model of diagnostic comorbidity to personality pathology. AB - Although the network model represents a promising new approach to conceptualizing comorbidity in psychiatric diagnosis, the model applies most directly to Axis I symptom disorders; the degree to which the model generalizes to Axis II disorders remains open to question. This commentary addresses that issue, discussing opportunities and challenges in applying the network model to DSM-diagnosed personality pathology. PMID- 20584372 TI - Aligning psychological assessment with psychological science. AB - Network analysis is a promising step forward in efforts to align psychological assessment with explanatory theory in psychological science. The implications of Cramer et al.'s analysis are quite general. Networks analysis may illuminate functional relations not only among observable behaviors that comprise psychological disorders, but among cognitive and affective processes that causally contribute to everyday experience and action. PMID- 20584373 TI - Comorbid science? AB - We agree with Cramer et al.'s goal of the discovery of causal relationships, but we argue that the authors' characterization of latent variable models (as deployed for such purposes) overlooks a wealth of extant possibilities. We provide a preliminary analysis of their data, using existing algorithms for causal inference and for the specification of latent variable models. PMID- 20584374 TI - Visualizing genetic similarity at the symptom level: the example of learning disabilities. AB - Psychological traits and disorders are often interrelated through shared genetic influences. A combination of maximum-likelihood structural equation modelling and multidimensional scaling enables us to open a window onto the genetic architecture at the symptom level, rather than at the level of latent genetic factors. We illustrate this approach using a study of cognitive abilities involving over 5,000 pairs of twins. PMID- 20584375 TI - An agenda for symptom-based research. AB - The network approach proposed by Cramer et al. suggests fascinating new directions of research on mental disorders. Research is needed to find evidence for the causal power of symptoms, to examine symptoms thoroughly, to investigate individual differences in edge strength, to discover etiological processes for each symptom, and to determine whether and why symptoms cohere into distinct mental disorders. PMID- 20584376 TI - Symptom networks and psychiatric categories. AB - The network approach to psychiatric phenomena has the potential to clarify and enhance psychiatric diagnosis and classification. However, its generally well justified anti-essentialism views psychiatric disorders as invariably fuzzy and arbitrary, and overlooks the likelihood that the domain includes some latent categories. Network models misrepresent these categories, and fail to recognize that some comorbidity may represent valid co-occurrence of discrete conditions. PMID- 20584377 TI - Extending the network perspective on comorbidity. AB - Cramer et al. make a good case for reconceptualizing comorbid psychopathologies in terms of complex network theory. We suggest the need for an extension of their network model to include reference to latent causes. We also draw attention to a neglected approach to theory appraisal that might usefully be incorporated into the methodology of network theory. PMID- 20584378 TI - Network models of psychopathology and comorbidity: philosophical and pragmatic considerations. AB - Cramer et al.'s account of comorbidity comes with a substantive philosophical view concerning the nature of psychological disorders. Although the network account is responsive to problems with extant approaches, it faces several practical and conceptual challenges of its own, especially in cases where the individual differences in network structures require the analysis of intra individual time-series data. PMID- 20584379 TI - Is there a contradiction between the network and latent variable perspectives? AB - First, we question whether Cramer et al.'s proposed network model can provide a viable scientific foundation for investigating comorbidity without invoking latent variables in some form. Second, the authors' claim that the network perspective is radically different from a latent variable perspective rests upon an undemonstrated premise. Without being demonstrated, we think the premise is potentially misleading. PMID- 20584380 TI - Network origins of anxiety and depression. AB - Cramer et al. contrast two possible explanations for psychological symptoms: latent variables (i.e., specific cause) versus a network of causality between symptoms. There is a third explanation: The reason for comorbidity and the reported network structure of psychological symptoms is that the underlying biological cause is a psychoneuroimmunoendocrine information network which, when dysregulated, leads to several maladaptive psychological and somatic symptoms. PMID- 20584381 TI - The network perspective will help, but is comorbidity the question? AB - Latent variable modeling has revealed important conundrums in the DSM classification system. We agree that the network perspective has potential to inspire new insights and resolve some of these conundrums. We note, however, that alone it cannot really help us understand etiology. Etiology, not comorbidity, is the fundamental question. PMID- 20584382 TI - Toward scientifically useful quantitative models of psychopathology: the importance of a comparative approach. AB - Cramer et al. articulate a novel perspective on comorbidity. However, their network models must be compared with more parsimonious latent variable models before conclusions can be drawn about network models as plausible accounts of comorbidity. Latent variable models have proven generative in studying psychopathology and its external correlates, and we doubt network models will prove as useful for psychopathology research. PMID- 20584383 TI - Questions about networks, measurement, and causation. AB - Cramer et al. present a thoughtful application of network analysis to symptoms, but certain questions remain open. These questions involve the intended causal interpretation, the critique of latent variables, individual variation in causal networks, Borsboom's idea of networks as measurement models, and how well the data support the stability of the network results. PMID- 20584384 TI - Symptoms as latent variables. AB - In the target article, Cramer et al. suggest that diagnostic classification is improved by modeling the relationship between manifest variables (i.e., symptoms) rather than modeling unobservable latent variables (i.e., diagnostic categories such as Generalized Anxiety Disorder). This commentary discusses whether symptoms represent manifest or latent variables and the implications of this distinction for diagnosis and treatment. PMID- 20584385 TI - Latent variable models are network models. AB - Cramer et al. present an original and interesting network perspective on comorbidity and contrast this perspective with a more traditional interpretation of comorbidity in terms of latent variable theory. My commentary focuses on the relationship between the two perspectives; that is, it aims to qualify the presumed contrast between interpretations in terms of networks and latent variables. PMID- 20584386 TI - Some mental disorders are based on networks, others on latent variables. AB - Cramer et al. persuasively conceptualize major depressive disorder (MDD) and generalized anxiety disorder (GAD) as network disorders, rejecting latent variable accounts. But how does their radical picture generalize across the suite of mental and personality disorders? Addictions are Axis I disorders that may be better characterized by latent variables. Their comorbidity relationships could be captured by inserting them as nodes in a super-network of Axis I conditions. PMID- 20584387 TI - Comorbidity: the case of developmental psychopathology. AB - In developmental psychopathology, differentiating between the coexistence and the clinical entity of two problem areas is of utmost importance. So far, logistic regression analysis has already provided helpful answers, as shown in studies on comorbidity of tic disorders. While the concept of bridging symptoms may be investigated adequately by both logistic regression and the network approach, the former (latent variable) seems to be of advantage with regard to the problems of multiple comorbidities and development. PMID- 20584388 TI - Comorbidity: cognition and biology count! AB - We agree with Cramer et al. that pure cases of behavioral disorders with no symptom overlaps are rare. However, we argue that disorders do exist and the network idea is limited and limiting. Networks of symptoms are observed mainly at behavioral levels. The core deficit is commonly at the cognitive or brain levels, and there the story is completely different. PMID- 20584389 TI - Looking at comorbidity through the glasses of neuroscientific memory research: a brain-network perspective. AB - As psychiatric illnesses have correlates in the brain, it is surprising that Cramer et al. make almost no reference to the brain's network character when proposing a network approach to comorbidity of psychiatric diseases. We illustrate how data from combined neuropsychological and functional and structural brain-imaging investigations could inform theoretical models about the role played by overlapping symptoms in the etiology of psychiatric comorbidity and the pathways from one disorder to another. PMID- 20584390 TI - The importance of modeling comorbidity using an intra-individual, time-series approach. AB - We suggest that the network approach to comorbidity (Cramer et al.) is best examined by using longitudinal, multi-measurement, intra-individual data. Employment of time-series analysis to the examination of the generalized anxiety disorder and major depressive disorder comorbidity enables a detailed appreciation of fluctuations and causal trajectories in terms of both symptoms and cognitive vulnerability. PMID- 20584391 TI - Consequences of a network view for genetic association studies. AB - Cramer et al's proposal to view mental disorders as the outcome of network dynamics among symptoms obviates the need to invoke latent traits to explain co occurrence of symptoms and syndromes. This commentary considers the consequences of such a network view for genetic association studies. PMID- 20584392 TI - Networks as complex dynamic systems: applications to clinical and developmental psychology and psychopathology. AB - Cramer et al.'s article is an example of the fruitful application of complex dynamic systems theory. We extend their approach with examples from our own work on development and developmental psychopathology and address three issues: (1) the level of aggregation of the network, (2) the required research methodology, and (3) the clinical and educational application of dynamic network thinking. PMID- 20584393 TI - The missing developmental dimension in the network perspective. AB - We welcome network theory as a tool for modelling the multi-directional interactions that characterise disease. However, we feel that Cramer et al. have neglected one important aspect: how diseases change over developmental time. We discuss principles such as fan in, fan out, bottlenecks, and common pathways, and argue that modelling these developmental aspects can be vital, particularly in deriving properly targeted treatments. PMID- 20584395 TI - The abandonment of latent variables: philosophical considerations. AB - Cramer et al.'s critique of latent variables implicitly advocates a type of scientific anti-realism which can be extended to many dispositional constructs in scientific psychology. However, generalizing Cramer et al.'s network model in this way raises concerns about its applicability to psychopathology. The model could be improved by articulating why a given cluster of symptoms should be considered disordered. PMID- 20584394 TI - Comorbidity in the context of neural network properties. AB - Cramer et al.'s network approach reconceptualizes mental comorbidity on the basis of symptom space originating from psychometric signatures. We argue that the advantages of this approach need to be regarded in the context of the multi-level functional organization of the neural substrate, ranging from neurogenetic to psychometric. Neuroelectric oscillations are proposed as a level-integrating principle. PMID- 20584396 TI - Precis of doing without concepts. AB - Although cognitive scientists have learned a lot about concepts, their findings have yet to be organized in a coherent theoretical framework. In addition, after twenty years of controversy, there is little sign that philosophers and psychologists are converging toward an agreement about the very nature of concepts. Doing without Concepts (Machery 2009) attempts to remedy this state of affairs. In this article, I review the main points and arguments developed at greater length in Doing without Concepts. PMID- 20584397 TI - Default knowledge, time pressure, and the theory-theory of concepts. AB - I raise two issues for Machery's discussion and interpretation of the theory theory. First, I raise an objection against Machery's claim that theory-theorists take theories to be default bodies of knowledge. Second, I argue that theory theorists' experimental results do not support Machery's contention that default bodies of knowledge include theories used in their own proprietary kind of categorization process. PMID- 20584398 TI - Carving nature at its joints using a knife called concepts. AB - That humans can categorize in different ways does not imply that there are qualitatively distinct underlying natural kinds or that the field of concepts splinters. Rather, it implies that the unitary goal of forming concepts is important enough that it receives redundant expression in cognition. Categorization science focuses on commonalities involved in concept learning. Eliminating "concept" makes this more difficult. PMID- 20584399 TI - Not different kinds, just special cases. AB - Machery's Heterogeneity Hypothesis depends on his argument that no theory of concepts can account for all the extant reliable categorization data. I argue that a single theoretical framework based on graphical models can explain all of the behavioral data to which this argument refers. These different theories of concepts thus (arguably) correspond to different special cases, not different kinds. PMID- 20584400 TI - An additional heterogeneity hypothesis. AB - In this commentary, I make three points concerning Machery's response to neo empiricism. First, his methodological critique fails to remove the threat that neo-empiricism poses to his conceptual eliminativism. Second, evidence suggests that there are multiple semantic codes, some of which are not perceptually based. Third, this representational heterogeneity thwarts neo-empiricism but also raises questions with respect to how we should "do without concepts." PMID- 20584401 TI - Unity amidst heterogeneity in theories of concepts. AB - This commentary raises two concerns with Machery's approach in Doing without Concepts. The first concern is that it may be possible to preserve a unified theory of concepts by distinguishing facts about concept individuation from facts about cognitive structures and processes. The second concern questions the sharpness of the distinction Machery draws between psychological and philosophical conceptions of concepts. PMID- 20584402 TI - Two uneliminated uses for "concepts": hybrids and guides for inquiry. AB - Machery's case against hybrids rests on a principle that is too strong, even by his own lights. And there are likely important generalizations to be made about hybrids, if they do exist. Moreover, even if there were no important generalizations about concepts themselves, the term picks out an important class of entities and should be retained to help guide inquiry. PMID- 20584403 TI - Concept talk cannot be avoided. AB - Distinct systems for representing concepts as prototypes, exemplars, and theories are closely integrated in the mind, and the notion of concept is required as a framework for exploring this integration. Eliminating the term "concept" from our theories will hinder rather than promote scientific progress. PMID- 20584404 TI - Eliminating the "concept" concept. AB - Machery suggests that the concept of "concept" is too heterogeneous to serve as a "natural kind" for scientific explanation, so cognitive science should do without concepts. I second the suggestion and propose substituting, in place of concepts, inborn and acquired sensorimotor category-detectors and category-names combined into propositions that define and describe further categories. PMID- 20584405 TI - Defending the concept of "concepts". AB - We critically review key lines of evidence and theoretical argument relevant to Machery's "heterogeneity hypothesis." These include interactions between different kinds of concept representations, unified approaches to explaining contextual effects on concept retrieval, and a critique of empirical dissociations as evidence for concept heterogeneity. We suggest there are good grounds for retaining the concept construct in human cognition. PMID- 20584406 TI - Hybrid vigor and conceptual structure. AB - Machery rightly points out a diverse set of phenomena associated with concepts that create challenges for many traditional views of their nature. It may be premature, however, to give up such views completely. Here I defend the possibility of hybrid models of concept structure. PMID- 20584407 TI - The faux, fake, forged, false, fabricated, and phony: problems for the independence of similarity-based theories of concepts. AB - Some things in our environment are not what they seem, and they provide a challenge to theories of concepts that emphasize similarity. Section 1 of my commentary explores a dilemma this situation creates for Machery. Section 2 describes a more general problem for prototype and exemplar theories. Section 3 locates a place for similarity-based concepts, and indicates an alternative to Machery's thesis. PMID- 20584408 TI - The function and representation of concepts. AB - Machery has usefully organized the vast heterogeneity in conceptual representation. However, we believe his argument is too narrow in tacitly assuming that concepts are comprised of only prototypes, exemplars, and theories, and also that its eliminative aspect is too strong. We examine two exceptions to Machery's representational taxonomy before considering whether doing without concepts is a good idea. PMID- 20584409 TI - Concepts are a functional kind. AB - This commentary focuses on Machery's eliminativist claim, that "concept" ought to be eliminated from the theoretical vocabulary of psychology because it fails to denote a natural kind. I argue for the more traditional view that concepts are a functional kind, which provides the simplest account of the empirical evidence discussed by Machery. PMID- 20584410 TI - From conceptual representations to explanatory relations. AB - Machery emphasizes the centrality of explanation for theory-based approaches to concepts. I endorse Machery's emphasis on explanation and consider recent advances in psychology that point to the "heterogeneity" of explanation, with consequences for Machery's heterogeneity hypothesis about concepts. PMID- 20584411 TI - Concepts and theoretical unification. AB - Concepts are mental symbols that have semantic structure and processing structure. This approach (1) allows for different disciplines to converge on a common subject matter; (2) it promotes theoretical unification; and (3) it accommodates the varied processes that preoccupy Machery. It also avoids problems that go with his eliminativism, including the explanation of how fundamentally different types of concepts can be co-referential. PMID- 20584412 TI - Where are nature's joints? Finding the mechanisms underlying categorization. AB - Machery argues that concepts are too heterogeneous to be a natural kind. I argue that the book does not go far enough. Theories of concepts assume that the task of categorizing warrants a unique set of cognitive constructs. Instead, cognitive science must look across tasks to find a fundamental set of cognitive mechanisms. PMID- 20584413 TI - Concepts versus conceptions (again). AB - Machery neglects the crucial role of concepts in psychological explanation, as well as the efforts of numerous "externalists" of the last 40 years to provide an account of that role. He rightly calls attention to the wide variation in people's epistemic relations to concepts - people's conceptions of things - but fails to appreciate how externalist and kindred proposals offer the needed stability in concepts themselves that underlies that variation. PMID- 20584414 TI - Why don't concepts constitute a natural kind? AB - Machery argues that concepts do not constitute a natural kind. We argue that this is a mistake. When appropriately construed, his discussion in fact bolsters the claim that concepts are a natural kind. PMID- 20584415 TI - Evidence of coordination as a cure for concept eliminativism. AB - I argue that Machery stacks the deck against hybrid theories of concepts by relying on an unduly restrictive understanding of coordination between concept parts. Once a less restrictive notion of coordination is introduced, the empirical case for hybrid theories of concepts becomes stronger, and the appeal of concept eliminativism weaker. PMID- 20584416 TI - Conceptual atomism rethought. AB - Focusing on Machery's claim that concepts play entirely different roles in philosophy and psychology, I explain how one well-known philosophical theory of concepts, Conceptual Atomism (CA), when properly understood, takes into account both kinds of roles. PMID- 20584417 TI - Banishing the thought. AB - The first seven chapters of Doing without Concepts offer a perfectly reasonable view of current research on concepts. The last chapter, on which the central thesis of the book rests, provides little actual evidence that using the term "concept" impedes scientific progress. It thus fails to demonstrate that this term should be eliminated from the scientific vernacular. PMID- 20584418 TI - Are prototypes and exemplars used in distinct cognitive processes? AB - We argue that Machery provides no convincing evidence that prototypes and exemplars are typically used in distinct cognitive processes. This partially undermines the fourth tenet of the Heterogeneity Hypothesis and thus casts doubts on Machery's way of splitting concepts into different kinds. Although Machery may be right that concepts split into different kinds, such kinds may be different from those countenanced by the Heterogeneity Hypothesis. PMID- 20584419 TI - Doing with development: moving toward a complete theory of concepts. AB - Machery proposes that the construct of "concept" detracts from research progress. However, ignoring development also detracts from research progress. Developmental research has advanced our understanding of how concepts are acquired and thus is essential to a complete theory. We propose a framework that both accounts for development and holds great promise as a new direction for thinking about concepts. PMID- 20584420 TI - The theoretical indispensability of concepts. AB - Machery denies the traditional view that concepts are constituents of thoughts, and he more provocatively argues that concepts should be eliminated from our best psychological taxonomy. I argue that the constituency view has much to recommend it (and is presupposed by much of his own theory), and that the evidence gives us grounds for pluralism, rather than eliminativism, about concepts. PMID- 20584421 TI - Developing without concepts. AB - We evaluate the heterogeneity hypothesis by considering the developmental time course and the mechanism of acquisition of exemplars, prototypes, and theories. We argue that behavioral and modeling data point to a sequential emergence of these three types of concepts within a single system. This suggests that similar or identical underlying cognitive processes - rather than separate ones - underpin representation acquisition. PMID- 20584422 TI - Parsimony and the triple-system model of concepts. AB - Machery's dismissive position on parsimony requires that we examine especially carefully the data he provides as evidence for his complex triple-system account. We use the prototype-exemplar debate as an example of empirical findings which may not, in fact, support a multiple-systems account. We discuss the importance of considering complexity in scientific theory. PMID- 20584424 TI - Dietary guidelines and goal-setting. PMID- 20584429 TI - Editorial. Interventional neuroradiology is dead! Long live endovascular therapy! PMID- 20584423 TI - Pathological implications of cell cycle re-entry in Alzheimer disease. AB - The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD. PMID- 20584430 TI - Editorial. Interventional neuroradiology in the United kingdom. PMID- 20584431 TI - Hereditary haemorrhagic telangiectasia in children. Endovascular treatment of neurovascular malformations. Results in 31 patients. AB - SUMMARY: Hereditary haemorrhagic telangiectasia (HHT) is a heterogeneous disease that may present with different clinical phenotypes and different clinical expressions. Concerning the neurovascular expressions of this disease, the paediatric age group in particular presents with potentially devastating symptomatic phenotypes. The purpose of this article was to review the therapeutic results of endovascular treatment of neurovascular malformations in children. A total of 31 children under the age of 16 were included in this retrospective analysis. All children were treated in a single centre. Twenty children presented with 28 arteriovenous (AV) fistulae including seven children with spinal AV fistulae and 14 children with cerebral AV fistulae (one child had both a spinal and cerebral fistulae). Eleven children had small nidus type AV malformations. All embolizations were performed in a single centre employing superselective glue injection. Follow-up ranged between three and 168 months (mean: 66 months) A total of 115 feeding vessels were embolized in 81 single sessions resulting in a mean overall occlusion rate of the malformation of 77.4% (ranging from 30 to 100%). Two of 30 patients (6.5%) died as a direct complication of the embolization procedure, two patients (6.5%) had a persistent new neurological deficit, eight patients (26.7%) were clinically unchanged following the procedure. In 11 patients (36.7%) an amelioration of symptoms but no cure could be achieved, six patients (20%) were completely asymptomatic following the endovascular procedure. In the surviving patients morphological complete occlusion was possible in twelve patients (38%), therapy is still not complete in six patients. Since the natural history of neurovascular manifestations of HHT in children is associated with a high morbidity and mortality, therapeutic intervention is mandatory. In most instances a morphological target can be identified, therefore even partial and staged treatment can be performed. Our results demonstrate that in 27/31 patients these targeted interventions resulted in stabilizing the disease, ameliorating the symptoms or even in curing the patient. The endovascular approach employing glue as the embolizing agent represents therefore a safe and efficient way to control the neurovascular phenotypes of HHT. PMID- 20584432 TI - Symptomatic Radionecrosis after AVM Stereotactic Radiosurgery. Study of 16 Consecutive Patients. AB - SUMMARY: The purpose of our study was to analyze the outcome of symptomatic radionecrosis following stereotactic radiosurgery for brain arteriovenous malformations. Of 225 patients treated by linear accelerator radiosurgery for brain AVM, 16 (7,1%) presented post-radiosurgery symptomatic radionecrosis on a mean follow-up period of 50 months (range 1-123 months). Once diagnosed with radionecrosis, 14 of 16 patients were subjected to high dose corticotherapy consisting of escalating doses of dexamethasone for several weeks. The mean interval of occurrence of new symptoms was 11.6 months post-radiosurgery (range 6 20 months). The mean time of follow-up was 2.9 years post radiotherapy ranging from seven months to eight years. Of the 16 patients with symptomatic radionecrosis, 11 (68,75%) showed complete resolution of symptoms while five (31,25%) showed improvement but still presented a neurological deficit at the closing date of the study. At the closing date, 11 patients (68.75%) had angiographically completely obliterated arteriovenous malformations while another two patients had an obliteration of 95% to 98% and one patient had a 98% obliteration with development of a new contralateral AVM. In our series, symptomatic radionecrosis occurred in 7.1% of patients treated with stereotactic radiosurgery for brain AVM. These patients where subjected to a prompt, high dose corticosteroid treatment and most presented symptom resolution or improvement with a fair obliteration rate, offering protection from bleeding. Permanent neurologic deficits attributable to radionecrosis occurred in 2.2% of our patient population treated with stereotactic radiosurgery for brain AVM. PMID- 20584433 TI - Accuracy of Voxel-Based and Algebraic Formula-Based Methods in Quantifying Cerebral Aneurysm Volume by 3D-Rotational Digital Subtraction Angiography. An In Vitro and In-Vivo Study. AB - SUMMARY: Accurate knowledge of cerebral aneurysm volume would be valuable in guiding the volume of embolized material required for optimal filling of an aneurysm sac and recording percentage volume filling. Algebraic volumes are frequently estimated by algebraic volume formulae. 3D digital subtraction angiography (DSA) aids endovascular treatment planning and yields volumetric data. Our aim was to define the accuracy of 3D-DSA in quantifying aneurysm volume using an automated voxel-based volumetric method (voxel volume method) and compare results to volumes calculated by ellipsoid and cylindrical algebraic formulae (algebraic volume method). We constructed 13 latex aneurysm moulds and measured their true volumes using a micropipette in-vitro. 3D-DSA was performed on contrast filled moulds and experimental volume estimated by both voxel and algebraic methods. In our in-vivo study we quantified the voxel and algebraic volumes from the 3D data sets of 75 cerebral aneurysms. The linear regression test provided correction values between voxel and algebraic methods. The in-vitro study showed that the voxel volume method was the most accurate (mean percentage deviation from true volume 3.7 +/- 3.5%; p=0.9). The ellipsoid method significantly underestimated - 11.2 +/- 13.6%; p < 0.05) and the cylindrical method overestimated (42.6 +/- 35.7%; p < 0.05) true aneurysm volume. Similar results were obtained in-vivo. While algebraic measurements could be corrected by an equation, the clinical usefulness of this equation is questionable due to the large volume range to achieve a 95% confidence interval. The voxel volume method is accurate in quantifying aneurysm volume. Aneurysms in-vivo do not conform to simple algebraic geometry. Aneurysm volume on 3D-DSA should be calculated by the voxel-based method and not by algebraic formulae. PMID- 20584434 TI - Endovascular Coiling of Aneurysm Remnants after Clipping in Patients with Follow up. A Single Center Experience. AB - SUMMARY: The vast majority of intracranial aneurysms can be obliterated completely with surgical clipping. However, postoperative remnants occur in about 4 to 8% of patients who undergo postoperative angiography. Endovascular embolization has been successfully performed in patients with postoperative aneurysm remnant and it may represent a therapeutic alternative to surgical reintervention. Twelve aneurysm remnants after surgical clipping were treated with endovascular embolization using GDC. All aneurysms were located in the anterior circulation. Our experience confirms the feasibility and relative safety of this treatment strategy that may be considered a valid alternative to reintervention. PMID- 20584435 TI - Rupture of a large vertebral artery aneurysm following proximal occlusion. AB - SUMMARY: Proximal occlusion of the vertebral artery is regarded as a safe and effective method of treating aneurysms of the vertebral artery or the vertebrobasilar junction unsuitable for treatment by neck clipping. Complications known to develop after this procedure include ischemic lesions of the perforators and other areas. There are only a limited number of reports on early rupture of aneurysm following proximal occlusion of the vertebral artery for the treatment of unruptured aneurysm. We recently encountered a case of large aneurysm of the vertebral artery identified after detection of brainstem compression. This patient underwent proximal occlusion of the vertebral artery with a coil and developed a fatal rupture of the aneurysm ten days after proximal occlusion. The patient was a 72-year-old woman who had complained of dysphagia and unsteadiness for several years. An approximately 20 mm diameter aneurysm was detected in her left vertebral artery. She underwent endovascular treatment, that is, her left vertebral artery was occluded with coils at a point proximal to the aneurysm. Her initial post-procedure course was uneventful. However, she suddenly developed right-side hemiparesis nine days after procedure. At that time, CT scan suggested sudden thrombosis of the aneurysm. Right vertebral angiography revealed a small part of the aneurysm. She was treated conservatively. Ten days after the procedure, she suffered massive subarachnoid haemorrhage. Both the present case and past reports suggest that proximal occlusion of the vertebral artery is effective in treating relatively large aneurysms unsuitable for treatment by neck clipping or trapping. However, when the bifurcation of the posterior inferior cerebellar artery (PICA) is distal to the occluded point in cases where the PICA bifurcates from the aneurysm or the neck region, blood supply to the aneurysm may persist because anterograde blood flow to the PICA may be preserved. Therefore, clinicians must consider the possibility of aneurysm rupture after proximal occlusion in the following cases: 1) when the aneurysm is large or giant, but non thrombosed; 2) when thrombosis occurs soon after the procedure; 3) when postoperative angiography shows partial filling of the aneurysm with contrast agent through the contralateral vertebral artery of basilar artery or the cervical muscle branches. PMID- 20584436 TI - Subarachnoid Haemorrhage from a Large Cerebral Aneurysm Visible only on Repeat Angiography. AB - SUMMARY: We report the case of a 49-year-old woman with a massive subarachnoid haemorrhage in conjunction with trauma. The initial cerebral angiography was normal. Three weeks later she had a second subarachnoid haemorrhage. A repeat angiography demonstrated an eight mm aneurysm of the internal carotid artery bifurcation, a region clearly normal in the previous angiography. PMID- 20584437 TI - Combined neuroform intracranial stent and bioactive matrix detachable coil for embolization of a broad-necked persistent primitive trigeminal artery aneurysm. A case report. AB - SUMMARY: We report a patient with a wide-necked aneurysm arising at the bifurcation of the right internal carotid artery and the persistent primitive trigeminal artery (PPTA) treated successfully by Matrix detachable coil occlusion and assisted by a Neuroform intracranial stent. First, a Neuroform self-expanding intracranial stent was delivered via a 5-F Guider Softtip XP and placed as desired, then the aneurysm dome was embolized with two Matrix detachable coils through the interstices of the stent. The aneurysm was 80% occluded angiographically and the parent artery was patent. DSA imaging six months after the procedure showed the aneurysm to be obliterated at angiography and the neck tissue thickness of the aneurysm to be increased, but the parent artery diameter was not impacted. We describe the case in detail and discuss our preliminary experience of using the Neuroform stent and Matrix detachable coils for the treatment of a PPTA wide-necked aneurysm. PMID- 20584438 TI - Emergency rescue primary stenting for atherosclerotic basilar artery occlusion with acute thrombosis. A case report. AB - SUMMARY: We demonstrate endovascular stent deployment for the treatment of atherosclerotic basilar artery occlusion with acute thrombosis. Application of a microstent without previous balloon dilatation resulted in vessel reopening and good clinical improvement. Emergency primary stent application can be technically feasible and improve the outcome in acute basilar artery occlusion and clinical status. PMID- 20584439 TI - N-butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistula. Presenting with subarachnoid haemorrhage. AB - SUMMARY: We report an unusual case of spinal dural arteriovenous fistula (SDAVF) presenting with subarachnoid haemorrhage (SAH). Cure was achieved with endovascular treatment with n-butyl 2- cyanoacrylate (NBCA). A review of the literature revealed five cases of cervical SDAVF that presented with SAH. None of these cases were treated with NBCA. PMID- 20584440 TI - Metachronous Multiplicity of Spinal Cord Arteriovenous Fistula and Spinal Dural AVF in a Patient with Hereditary Haemorrhagic Telangiectasia. AB - SUMMARY: HHT (Hereditary Haemorrhagic Telangiectasia or Rendu Osler Weber disease) is a known autosomal dominant dysplasia. The first clinical presentation of HHT in a child may be a cerebral or spinal AVM. We present the case of a young boy with HHT who had a previous spinal cord AVF treated by surgical obliteration and then presented with a spinal dural AVF nine months later. This patient had surgical obliteration of a spinal cord perimedullary AVF and subsequently developed a new spinal dural AVF at a different level. The diagnosis was made by spinal MR imaging and spinal angiography. PMID- 20584441 TI - Editorial. Why "neuroendovascular surgery"? PMID- 20584442 TI - Letter to the editor. Anticoagulant and antithrombotic agent use in intracranial aneurysm treatment call for a consensus. PMID- 20584444 TI - The anastomotic venous circle of the base of the brain. AB - SUMMARY: Adjacent to the arterial circle of Willis at the base of the brain, there is an anastomotic circle of veins linking the right and left halves of the cerebral deep venous system. This venous circle is formed by anterior and posterior transverse anastomotic channels (the anterior and posterior communicating veins), and paramedian longitudinal vessels (the basal veins of Rosenthal). This collateral venous network has received considerably less attention than its arterial counterpart, but is its functional homologue. Although inconstant, it can be seen readily with current neuroimaging techniques including three-dimensional digital subtraction venographic phase 3D arteriography (3D-DSV) and CT venography (CTV). The venous circle represents a route of contralateral venous drainage that may become important, particularly when segments of the basal vein are absent (with or without complex DVA), or in high flow states including arteriovenous shunts that access the deep venous system.We review the gross anatomy and provide examples of the radiologic imaging of this venous circle. PMID- 20584443 TI - Vertebroplasty in the treatment of spine disease. AB - SUMMARY: We report our experience in the treatment of thoracic and lumbosacral spinal pain due to vertebral bone fractures. This pathology can be related to osteoporosis but also to metastatic disease and less frequently vertebral haemangioma. From April 2001 through December 2004 we treated 238 patients for a total of 455 vertebral bodies. 175 patients had osteoporosis, 70 had metastasis and 13 had vertebral haemangioma. Sacroplasty was performed in six patients to obtain a cement filling of sacral metastasis. The procedures were mostly performed under fluoroscopy and only in cases of metastasis or sacroplasty was CT/fluoroscopy guidance preferred for optimal filling of the area of osteolysis. We evaluated the results at six and 18 months follow-up and analysed the incidence of new vertebral fractures, vascular and disk leakage and the incidence of major and minor complications. Biopsy was performed only in doubtful cases. We obtained different results considering the etiology of the disease. We obtained a 92% success rate at six months follow-up and 89% success at 18 months follow-up in osteoporosis, a 77% and 72% success rate at six and 18 months follow-up in metastastic patients, and no change at six and 18 months follow-up in patients with vertebral haemangioma in which the success rate was of 95%. We noted extravertebral leakage in 41% of vertebral bodies of which 31% were treated at the level of the vascular space and only 10% at the level of the disk space, and symptomatic in only two cases (acute compressive radiculitis, medically treated and resolved within a month). Six patients presented new fractures in the adjacent vertebral body and 30% had a partial recovery in the height of the vertebral body with kyphosis curve reduction. Vertebroplasty is a good technique to obtain spine pain relief and has a low incidence of side effects. Good quality equipment is important to obtain these results. PMID- 20584445 TI - Pathology of Stented Common Carotid Aneurysm in Dogs. Comparison between Stenting and Stent-Assisted Coiling. AB - SUMMARY: To elucidate focal successive histological responses of the neck of wide necked aneurysm after single stent implantation and stent-assisted coiling, an experimental wide-necked aneurysm model was surgically created in bilateral common carotid arteries of adult dogs. Balloon-expandable porous stents were positioned across the aneurysm necks on both sides. The aneurysm cavity of one side was additionally loosely coiled with Gugliemi detachable coils after stent implantation. The dogs were followed up with ultrasonography and angiography, then sacrificed at two days, one month, and one year and the aneurysm specimen was subjected to macro, micro, and electron microscopic observation. Stent implantation and coiling was successful in eight dogs. This investigation observed that single stent implantation slowed down the blood flow within the aneurysm, but barely induced thrombosis within the aneurysm. There was neointima formation over the stent mesh without thrombus within the aneurysm cavity, but it did not cover the whole aneurysm neck at one year.Aneurysms treated with stent assisted coiling showed thrombosis within the aneurysms and neointima formation over the whole aneurysm orifice. These results suggest that the neointima could develop over bare stent filament without thrombus within the aneurysm cavity, coils could enhance thrombosis within the aneurysm cavity and facilitate neointima formation over the aneurysm orifice. Stent-assisted coiling may be an alternative option for the treatment of wide-necked aneurysms. PMID- 20584446 TI - Recurrent or new symptomatic cerebral aneurysm after previous treatment. AB - SUMMARY: With the establishment of endovascular coiling as a successful treatment for symptomatic cerebral aneurysms, attention is now being directed at the durability of this treatment. If this is to be accurately done it will be important to understand the causes of symptomatic aneurysm presentation after previous treatment. In order to assess this we undertook a retrospective review, covering the four year period from 2000 to 2004, of all patients re-presenting with a symptomatic saccular aneurysm after previous treatment. Seven patients were identified, six presenting with subarachnoid haemorrhage (SAH) and one with a third cranial nerve palsy. Three patients had incomplete clipping of their aneurysms and all presented within months of their initial treatment. The other four patients presented between five and 20 years after primary treatment and all were felt to have new cerebral aneurysms. Two of these patients had aneurysms develop at the same location as their previously treated lesions, however these were still felt to be new aneurysms rather than re-growth or recurrence because of their morphology. Based on our findings it would appear that development of a new cerebral aneurysm after clipping is more of a risk than aneurysm recurrence from treatment failure. This will need to be considered when evaluating re presentation after treatment by either coiling or clipping and more importantly, perhaps we should be directing more attention to preventing disease progression rather than treatment failure. PMID- 20584447 TI - Carotid blowout treated by direct percutaneous puncture of internal carotid artery with temporary balloon occlusion. AB - SUMMARY: Direct percutaneous puncture of a cervical carotid pseudoaneurysm for coil placement or acrylic embolization is described for the endovascular management of acute carotid blowout. However, direct puncture of the internal carotid artery (ICA) for the endovascular management of carotid blowout has not been described. We report a difficult case of acute carotid blowout syndrome in a patient who had radiation- induced occlusion of the right common carotid artery with vasculopathy and pseudoaneurysm in the right cervical ICA. Collaterals from the branches of the controlateral external carotid artery (ECA) anastomosed with branches of right ECA supplied the vasculopathy. We performed direct percutaneous puncture of the bulb of the right ICA using a spinal needle and placed fiber coils to occlude antegrade flow of the artery. During the injection of a mixture of N-butyl cyanoacrylate and lipiodol oil for embolization of the remaining carotid bulb, we transiently inflated an occlusion balloon in the controlateral common carotid artery to further arrest antegrade flow in the ICA. The vasculopathy and pseudoaneurysm of the right cervical ICA were successfully embolized, with preservation of the distal branches of the right ICA. PMID- 20584448 TI - PHACE Syndrome: Persistent Fetal Vascular Anomalies. A Case Report. AB - SUMMARY: PHACE(S) syndrome is an acronym for neurocutaneous disease encompassing the expression of (P) posterior cranial fossa malformations, (H) facial haemangiomas, (A) arterial anomalies, (C) aortic coarctaion and other cardiac defects, (E) eye abnormalities and (S) for sternal malformation or stenotic arterial diseases. We report on a case of PHACE syndrome complete expression with persistent fetal vascular anomalies unusually in a 55-year-old women with large bilateral facial and neck haemangioma and posterior fossa circulation insufficiency. PMID- 20584449 TI - Traumatic carotid-cavernous fistula: endovascular treatment with onyx and coils. AB - SUMMARY: Carotid cavernous fistulas (CCF) are mostly post-traumatic and are due to a tear of the internal carotid artery (ICA) inside the cavernous sinus. The improvement of endovascular techniques with venous approach enables the preservation of internal carotid artery patency in most cases when detachable balloons fail in order to reconstruct and repair the tear in the ICA. The case described here has a giant aneurysmatic dilatation of the cavernous sinus and inferior petrosal sinus. We associate coils and Onyx to occlude the lesion preserving and repairing the large hole of the fistula. PMID- 20584450 TI - Traumatic carotid cavernous fistula: failure of endovascular treatment with two stent-grafts. AB - SUMMARY: We describe an unconventional endovascular approach in a young patient with large highflow traumatic carotid cavernous fistula that could not be treated by detachable balloon procedure. Two coronary stent-grafts were used to close the large tear of internal carotid artery. After the failure of stenting procedure, the fistula was successfully treated by trapping with two detachable balloons. PMID- 20584451 TI - Dural arteriovenous fistulas: unusual access routes in the elderly. AB - SUMMARY: Transvenous embolization is effective in the treatment of an intracranial dural arteriovenous fistula (DAVF). Retrograde venous access to the fistula may be limited by associated sinus thrombosis, as in the two cases here reported. Unusual curative access routes were performed: direct superior ophthalmic vein puncture and through a small craniectomy, packing the sinus with detachable coils. When traditional routes proved impossible, unusual access routes must be devised. PMID- 20584452 TI - Abrupt Flow Arrest in the Internal Carotid Artery during Carotid Artery Stenting Using the Parodi Anti-Emboli System. AB - SUMMARY: We report a rare complication of carotid artery stenting (CAS) in a patient with severe carotid artery stenosis.CAS with a protection of the Parodi Anti-Emboli System was complicated by an abrupt flow arrest in the internal carotid artery before the guidewire passage through the stenotic site. PMID- 20584453 TI - Intracranial Arterial Dissection Related to HIV Infection. A Case Report with Histology. AB - SUMMARY: There are many reasons for patients infected with human immunodeficiency virus (HIV) to develop cerebrovascular disease. The HIV virus itself however may be a cause of vessel wall pathology. We present a clinical and pathological study of a patient who was HIV positive and presented with a subarachnoid haemorrhage. Cerebral angiography and later histology confirm that there was extensive vessel wall injury with dissection and a false aneurysm of the right middle cerebral artery. PMID- 20584454 TI - Errata Corrige. Interv Neuroradiol 11: 241-246, 2005. Cerebral Arteriovenous Malformation Embolized through Persistent Primitive Hypoglossal Artery. A Case Report. AB - SUMMARY: Carotid-vertebral anastomoses are commonly detected as incidental findings. But sometimes these channels are important for the clinical condition of the patient. Here a case of right thalamo-capsular arteriovenous malformation is described where a persistent primitive hypoglossal artery was the only route for embolization of the arteriovenous malformation. PMID- 20584456 TI - Brain Arteriovenous Malformations (BAVMs) in Thailand: Therapeutic Experience and Clinical Outcomes in Ramathibodi Hospital. PMID- 20584455 TI - Therapeutic management of cerebral arteriovenous malformations. Present role of interventional neuroradiology. AB - This chapter summarizes the authors' experience in the endovascular therapy of cerebral arteriovenous malformations (AVMs). This clinical series includes 660 patients treated from 1980 to 2005. The first 148 patients were treated at University Hospital, in London, Ontario Canada, in association with Drs. Allan Fox, Dave Pelz, John Girvin and Charles Drake. The next 512 patients were treated at UCLA Medical Center, Los Angeles, California in association with Drs. Gary Duckwiler, Reza Jahan, Jacques Dion, Pierre Gobin, Neil Martin and John Frazee. Only patients treated with superselective endovascular/intraoperative catheterization and embolization of avm arterial feeders were included. Cerebral arteriovenous malformations treated by non-selective injection of beads in ICA or vertebral arteries were excluded. Modern neuroimaging modalities associated to the anatomical, topographic and functional evaluations of cerebral avms such as brain CT and CTA, MRI, MRA and functional MRI are all utilized at UCLA Medical Center. They have become essential in the therapeutic management of avms closely related to cerebral eloquent areas (figure 1). PMID- 20584457 TI - Management of Brain AVMs at Bicetre: a Comparison of Two Patient Cohorts Treated in 1985-1995 and 1996-2005. PMID- 20584458 TI - Endovascular treatment of cerebral arteriovenous malformations with emphasis on the curative role of embolisation. AB - SUMMARY: Valavanis A, Pangalu A, Tanaka M. Endovascular treatment of cerebral arteriovenous malformations with emphasis on the curative role of embolisation. Schweiz Arch Neurol Psychiatr 2004;155:341-7. Cerebral arteriovenous malformations are complex and only partially understood vascular lesions of the central nervous system with a natural history characterised by significant morbidity and mortality mainly due to an increased hemorrhagic risk, Microneurosurgical removal, radiosurgical obliteration and neuroendovascular embolisation are the principal therapeutic modalities applied individually or in various combinations according to varying selection criteria for the treatment of cerebral arteriovenous malformations. In this context embolisation plays a central role cither as a complementary or as the sole treatment technique. This report summarises the evolutive 18 years of continuous experience of the senior author with the neuroradiological evaluation and endovascular treatment of 644 patients with a cerebral arteriovenous malformation. Special emphasis is given to the underlying concepts and specific endovascular techniques developed for the complete, i.e. curative embolisation of cerebral arteriovenous malformations. Precise angiographic analysis of the vascular composition and intrinsic angioarchitecture of the nidus of the arteriovenous malformation by super selective microcatheterisation is required to identify the types of feeding arteries and patterns of their supply, the number and vascular connections of nidal compartments, the types of arteriovenous shunts, the morphology of the vascular spaces composing the nidus and the number and exit patterns of draining veins. Complete angiographic investigation for recognition of secondarily induced phenomena of the cerebral vasculature, such as arterial and venous high-flow angiopathy and so-called perinidal angiogenesis is essential for a comprehensive evaluation and assessment of the associated haemorrhagic risk. Based on a precise topographic classification, detailed angioarchitectural analysis, application of superselective multimicrocatheterisation techniques along with a controlled intranidal injection of non-absorbable liquid embolic materials, nearly 40% of cerebral arteriovenous malformations can be completely and stably obliterated and therefore curatively treated by single session or multistaged embolisation with a morbidity of 1.3% and a mortality of 13%. which arc lower than the known natural history of this disease. PMID- 20584459 TI - Brain AVM Embolization. Retrospective Study Concerning 728 Patients Followed between 1984 and 2004. PMID- 20584460 TI - Endovascular treatment of brain arteriovenous malformations: the toronto experience. PMID- 20584461 TI - Embolization as one modality in a combined strategy for the management of cerebral arteriovenous malformations. AB - SUMMARY: We attempted to assess clinical results of management of cerebral arteriovenous malformation using a combination of endovascular, surgical and radiotherapeutic approaches. We retrospectively reviewed the angiographic and clinical data on prospectively collected consecutive patients treated by embolization from 1994 to 2004. The general philosophy was to attempt treatment by a combination of approaches only when an angiographic cure was likely or at least possible. The clinical outcome was assessed according to the modified Rankin scale. Although 404 patients were collected, complete files and follow-ups are available for 227 or 56% only. Most patients presented with hemorrhages (53%) or seizures (23%). The final management consisted in embolization alone in 34%, embolization followed by surgery in 47%, embolization and radiotherapy in 16%, and embolization, surgery and radiotherapy in 3% of patients. The embolization procedure itself could lead to an angiographic cure in only 16% of patients. When the management strategy could be completed, the cure rate increased to 66%. Complications of embolization occurred in 22.6% of patients. Overall clinical outcome was excellent (Rankin 0) in 43%, good (Rankin 1) in 38%, fair (Rankin 2) in 10%, poor (Rankin 3-5) in 2%, and the death rate was 7%. A combined strategy initially designed to provide angiographic cures cannot be completed in a significant number of patients; the total morbidity of treatment remains significant. There is no scientific evidence that cerebral arteriovenous malformations should be treated, and no clinical trial to prove that one approach is better than the other. Various treatment protocols have been proposed on empirical grounds. Small lesions can often be eradicated, with surgery when lesions are superficial, or with radiation therapy for deeper ones. There has been little controversy regarding therapeutic indications in these patients (1). The management of larger AVMs, sometimes in more eloquent locations, is much more difficult and controversial (2-4). Endovascular approaches have initially been developed to meet this challenge (5,6). It became quickly evident that embolization alone would rarely suffice to completely cure these lesions. The philosophy behind combined approaches is founded on 2 opinions: 1) There is no proven value of partial embolization, not even "partial benefits", and treatment should aim at an angiographic cure (7) and 2) By appropriately tailoring all available tools to each situation, such a cure could be reached with minimum or reasonable risks. We have used such a combined strategy for more than a decade now. Endovascular techniques and materials have evolved, and it is perhaps possible today to reach a cure by embolization alone in a larger proportion of patients than before (8). Aggressive embolizations, aiming for an endovascular cure, even sometimes in large lesions, have recently been promoted for their power or criticized for their risks (9). But before evaluating the advantages and inconveniences of new treatments, it may be wise to review the results we could achieve with a conventional approach combining endovascular, surgical and radiotherapeutic techniques. PMID- 20584462 TI - Combined Treatment of Brain AVMs: Analysis of Five Years (2000-2004) in the Verona Experience. PMID- 20584463 TI - Endovascular Treatment of AVMs in Glasgow. PMID- 20584464 TI - Intra-arterial Embolization in the Treatment of Brain Arteriovenous Malformations. AB - SUMMARY: The crucial question - treat or not a brain arteriovenous malformation - has been the object of many studies, sometimes contradictory. The authors analyse retrospectively, clinically and angiographically, the results of the intra arterial embolization in the treatment of 106 patients with brain arteriovenous malformation. The endo- vascular therapy was palliative or curative in 46% of the cases, in 30% of the patients the embolization was pre-surgery and in 18% the intra- arterial occlusion was pre-radiosurgery. In 6% the therapeutic protocol included embolization with surgery and radiosurgery. Cyanocrylate was used in 89% of the cases, and in 10% of the patients the embolic material used was Ethylene - vinyl alcohol copolymer - EVOH (Onyx). In this series 11% of total morbidity occurred - transitory in 8% and settled with permanent neurological deficit in 3% of the patients. The mortality post-embolization was 2% and the total mortality post-embolization and surgery was 3%. Total angiographic exclusion immediately post-embolization was confirmed in 24% of the cases. The mean period for clinical and angiographic follow-up was 38 months. 72 patients - 77% of the cases discharged from hospital showed complete exclusion of the lesion after the different combined therapeutic strategy - embolization, surgery and radiosurgery. New retrospective and long-term prospective studies based on the actual therapeutic protocols and new embolic agents are necessary to be able to evaluate accurately a new therapeutic reality in the brain arteriovenous malformations. PMID- 20584465 TI - Ectatic and Occlusive Diseases of the Venous Drainage System of Cerebral Arteriovenous Malformations (AVMs) - with Emphasis on Spectacular Shrinking Neurological Deficits after Embolization. AB - During reviewing cases with AVM, the author noticed that stenotic and occlusive changes of the draining veins are commonly seen in high flow cerebral AVMs. However, little attention has been paid to these venous diseases until ectatic veins, generated in the upstream of the venous system, cause mass effect to the surrounding structures, or redistribution and shunting toward regional veins became insufficient after they are markedly overloaded or occluded. Cases with such venous abnormality are clinically important because of the possibility of dramatic improvement of neurological deficits after embolization of AVMs. Following presenting treatment results of 177 AVM case, the author is going to present five cases with abnormality in the Galenic venous system and two cases with abnormality in cortical veins associating with high flow cerebral AVMs. Consideration will be made on symptomatology and pathophysiologic mechanism of venous abnormalities associating with high flow cerebral AVMs. PMID- 20584466 TI - The Characters of Images and Endovascular Embolization for High Risk Cerebral AVM. AB - SUMMARY: The high risk cerebral AVM can do great harm to people in case of hemorrhage .The goal of aathis paper is to discuss the characters of images and the technical manipulate of endovascular embolization for high risk cerebral AVM with bleeding. Fifty-six cases of high risk cerebral AVM with bleeding were confirmed by CT?MRI?and approved by whole cerebral DSA. Depended on the nidus of AVM, the superselective endovascular embolization with NBCA or embolization combined with radiological surgery was chosen. The nidus was eliminated for 100% in 36 cases after embolization for 1 to 3 processes. The rebleeding was found in 2 cases with new growth and survival aneurysm in nidus during the following period and treatment with Y-knife, and cured by second embolization. These are the main causes of brain bleeding composed of aneurysm and aneurysmlike dilation beside and located at the nidus, fine draining veins, and growth in ventricles. It is the favourable for the preference to eliminate the aneurysm in AVM during embolization to prevent brain from bleeding. PMID- 20584467 TI - Brain arteriovenous malformations technical note of endovascular treatment with glubran(r). PMID- 20584468 TI - Basics and Principles in the Application of Onyx LD Liquid Embolic System in the Endovascular Treatment of Cerebral Arteriovenous Malformations. PMID- 20584469 TI - Endovascular Treatment of Cerebral AVM: Our Experience with Onyx. AB - SUMMARY: We have been using Onyx, a non-adhesive liquid polymer, to treat cerebral AVMs endovascularly since 1999. During this time we have treated 45 consecutive, unselected patients. From the outset this product brought about a change in our approach to treating this type of lesion because of the different injection behaviour observed for this material compared with the adhesive Histoacryl that had been employed until then. The object of this article is to assess the results achieved by our team using this new embolic agent, following angiographic and clinical follow- up of cases for a minimum of six months and a maximum of five years (mean: two years). We propose new categories of cerebral AVM based on the expected behaviour of Onyx within the nidus. Our appraisal indicates that we have improved our angiographic results, achieving complete occlusion of the malformation in 22% of cases and over 80-% closure in 69% of cases. The morbimortality rate for the procedure was 18%. PMID- 20584470 TI - Endovascular treatment of brain arteriovenous malformations using onyx: preliminary results of a prospective multicenter study. AB - SUMMARY: The main final goal of the treatment of brain AVMs is to prevent bleeding and to obtain a complete occlusion of the nidus. The strategy of treatment of brain arteriovenous malformations (AVM) has to be defined by a multidisciplinary team and will usually combine several modalities (surgery, radiosurgery, embolization). Embolization is generally the first step of treatment. Occasionally embolization is able to completely occlude a small AVM. Otherwise embolization is the first step before surgery or radiosurgery. Several embolic agents have been proposed for embolization of brain AVMs like particles or cyanoacrylates. The main disadvantage of particles is the high frequency of recanalization. The cyanoacrylates are probably more appropriate, providing a permanent occlusion. However, due to the polymerizing characteristics of the glue, the time of injection is relatively short (few seconds or minutes) and a complete or substantial occlusion of the nidus is difficult to obtain, especially in the case of medium or largesized AVMs. Onyx is a nonadhesive liquid polymer made of a mixture of ethylene-vinyl-alcohol copolymer and dimethylsulfoxide. The theoretical advantage of a nonadhesive liquid is to eliminate the risk of gluing the microcatheter and subsequently to perform a more durable injection with a larger amounts of agent delivered in a single injection. Several French centers have undertaken a prospective, multicentric study to evaluate the clinical value of Onyx in embolization of brain AVMs. As required, 50 patients were included. Preliminary results are presented regarding the first 48 patients, the last 2 patients being included after writing of this paper. The treatment is now completed in 15 patients. As expected, it was possible with Onyx to perform long duration injections (5 to 70 minutes with a mean of 34 minutes). Volumes injected per session were also important (0.25 to 6 ml with a mean of 1.6 ml). According to the clinical experience of the centers, duration and volume injected were most important with Onyx than with cyanoacrylates. Out of the 15 patients for whom embolization is now completed, 14 had a percentage of occlusion of the nidus greater than 60% (with 2 complete occlusion). With regard to procedural complications, four acute postembolization hemorrhages (APEH) were observed (8% per patient, 4% per procedure). This rate of APEH is in the same range as with cyanoacrylates. PMID- 20584471 TI - Endovascular Treatment of Cerebral AVMs with a New Material: Onyx(R). Partial Results. PMID- 20584472 TI - Endovascular Treatment of Cerebral AVM with Onyx - Initial Experience. AB - SUMMARY: Five patients (M:2, F:3; Age range 9-51; N=30 yrs) with cerebral AVM were managed with Onyx embolization through endovascular route in last three months. Two patients had complete occlusion of AVM following embolisation. In remaining three, one had 95% occlusion and other two had 70% and 50% occlusion respectively. No procedural related complications were observed immediately following procedure. PMID- 20584473 TI - Clinical Analysis of 50 Cases of BAVM Embolization with Onyx, a Novel Liquid Embolic Agent. AB - SUMMARY: To report the embolization technique of using Onyx, a new liquid embolic agent, to treat cerebral arteriovenous malformations (AVMs) as well as its efficacy. 38 cases of cerebral AVMs located in eloquent area (motor, speech, visual nerve center), 9 in deep cerebral area, and another 3 cases in cerebellar hemisphere. The diameter of AVMs was smaller than 3cm in 10 cases, 3-6cm in 30 cases, and larger than 6cm in 10 cases.A 6F sheath was placed into the femoral artery after Selding's puncture. After a 6F guiding catheter was introduced into the internal carotid artery or vertebral artery, Ultraflow or Marathon microcatheter could be navigated into the nidus of AVMs.A long-slow injection of Onyx under fluoroscopic control was performed to embolize cerebral AVMs by adopting the "plug and push" technique. 10 AVM cases (20.0%) were considered to be totally occluded with Onyx in this group, 3 cases of which were found no regrowth by a 6-month follow-up. 25 cases (50%) were subtotally occluded while another 15 cases (30%) were partially embolized. Complications include: (1) severe cerebral hemorrhage occurred in three cases, two of them left hemiplegia after hematoma resection. (2) mild hemiplegia occurred in one lager frontal AVM patient. (3) mild visual deficit was left in one larger occipital AVM case. There was no severe complication in other 45 patients. Onyx has unique and distinctive superiority in treating cerebral AVMs. Nonetheless, the correct embolization technique should be learned to achieve good clinical results and to avoid complications. The long-term efficacy of Onyx embolization needs to be followed up. PMID- 20584474 TI - Brain AVM Embolization with Onyx(R): Analysis of Treatment in 34 Patients. AB - SUMMARY: The endovascular approach to arteriovenous malformations (AVM) using different embolizing agents is a well-established treatment option. This report assesses the results of our experience using a non "glueing" embolic material available for several years, commercially known as Onyx(R). We used Onyx to treat 34 consecutive patients in the last four years. All patients were treated in the same department by the same neuroradiological team, with a strictly repetitive technical strategy and procedural protocol. All our patients presented AVMs with Spetzler Grade 3 or more, because in our Institution Grade 1 or 2 AVMs are directly treated by surgical approach. We adopt a multidisciplinary treatment approach (embolization, surgery, radiotherapy) by which embolization is construed as work in progress offering definitive treatment of AVMs without severe risks. Embolization is mainly undertaken as the first step before surgery, to reduce flow and size of the AVM by a "targeted" technique. In addition to reducing lesion size, endovascular treatment aims to seal off AVM areas anatomically or haemodynamically complex for surgical treatment. Occasionally, the reduction in size allows a radiosurgical approach. Embolization seldom results in a definitive cure of AVMs. At the end of multimodal approach, we obtained the complete and definitive cure of AVM in 21/34 patients (two complete obliteration with interventional technique, 19 in combination with surgery); to these were added 5/34 patients who received radiosurgical therapy. No major complications arose during endovascular treatment. One patient had transitory (36 hour) impaired right arm pronation. The CT scan disclosed an asymptomatic mild SAH in the left sylvian fissure but no ischaemic areas. One patient still in treatment died from fatal rebleeding (the clinical onset had been with haemorrhage two weeks before the session) 12 days after the embolization. Excellent or good clinical outcome was obtained in 23/26 patients who completed the therapeutic protocol. Outcome was conditioned by focal symptoms present on admission in three patients due to haemorrhagic onset, but only one patient presented a severe disability on discharge. In our view, the main problem of Onyx is that the apparently easier approach will probably lead to a wider diffusion of these procedures. AVMs are extremely difficult and dangerous to treat: this is not affected by the quality of the embolizing agents used and must be kept in mind at all times. PMID- 20584475 TI - Computer simulation of flow dynamics in paraclinoidal aneurysms. AB - SUMMARY: Endovascular treatment, which is very useful method especially for paraclinoidal aneurysms, has the limitations of coil compaction and recanalization, which are difficult to predict. We tried to understand flow dynamic features, one of the important factors of such problems, using computer flow dynamics (CFD) simulations. CFD simulations were made in paraclinoidal aneurysm model of different size and protruded directions. Flow patterns, flow velocities and pressure are analyzed. Although the pressure on the aneurismal orifice is highest in the aneurysm protruding vertically - upward, the flow velocity is highest in the superior-medial protruding one. Significant difference is not observed in either flow patterns, flow velocities or pressures on the aneurismal orifices between the sizes of aneurismal sac. Among paraclinoidal aneurysms, an aneurysm protruding to superior-medially receives the most severe haemodynamic stresses at the orifice and the aneurysm size does not cause significant differences in the aspect of flow dynamics. It should be considered in the treatment of such aneurysms. PMID- 20584476 TI - Carotid artery stenting: experience of a single institute in china. AB - SUMMARY: Concern regarding the safety of Carotid angioplasty and stenting (CAS) exists because of the risk of cerebral embolization during the procedure. The purpose of this article is to discuss that technology modification may improve the outcomes of this procedure. Between October 1997 and October 2004, 439 consecutive patients with 478 stenotic carotid arteries were treated. 284 vessels were stented without the use of embolic protection devices and 194 vessels with protection. Among cases not using protection device, 201 arteries were stented with predilation alone, 63 with postdilation alone, six with both pre- and post dilation, two with neither and twelve were stented with balloon expandable stents. The technical success of 100%.The combined stroke and death rate during the procedure and the 30-day follow-up at 30 days was 1.67% overall. Three (0.63%) deaths occurred; one was due to a major infarction secondary to stent breakage, and two died of massive reperfusion intracerebral haemorrhage. There were total six ischemic stroke, of the five ischemic strokes wich developed in nonprotection group, two were among 201 cases with predilation alone (0.99%), which developed after stent deployment and postprocedure, and three among 63 cases with postdilation alone (4.76%), which developed immediately after postdilation. The incidence of ischemic stroke was lower among those who were stented with predilation alone than among those who were stented with postdilation alone. This likely results from reduced intimal injury and decreased risk of embolic complications. PMID- 20584477 TI - Retrospective Study of Complications Arising during Cerebral and Spinal Diagnostic Angiography from 1998 to 2003. AB - SUMMARY: This retrospective study aimed to assess the percentage of complications in the daily practice of cerebral and spinal cord diagnostic angiography at our institution and to compare this with literature reports published in the last twenty years and guidelines for angiography. From 1(st) December 1998 to 1(st) December 2003 2154 patients underwent digital angiography for a total of 5996 vessels selected. Three neurological complications arose during angiographic procedures in the five year period. * Focal neurological deficit resolving within 24h in two patients, * Permanent neurological deficit in one patient. There were no adverse systemic reactions to contrast medium. Retrospective analysis of our cohort disclosed a complication rate of 0.1% for transient neurological complications and 0.05% for permanent deficits. PMID- 20584478 TI - Combined effects of embolization and hypofractionated conformal stereotactic radiotherapy in arteriovenous malformations of the brain. AB - SUMMARY: There are three major treatment options for cerebral AVMs; surgery, embolization and radiosurgery. Embolization may be effective to reduce the size and density but completely obliterates AVMs only in a minority of cases. Radiosurgery may be an alternative to resection, especially in smaller AVMs. Large AVMs have been considered difficult to treat safely and effectively with single fraction radiosurgery. Hypofractionated conformal stereotactic radiotherapy (HCSRT) alone or in combination with embolization may be an alternative treatment. Embolization may reduce the volume and density of AVMs, followed by HCSRT, allowing a safe delivery of a higher total dose of radiation than possible with a single fraction. Sixteen patients with AVMs were treated with embolization and HCSRT. Embolization was performed in 1-6 (median 2) sessions. HCSRT was delivered in 5 fractions with 6-7 Gy each to the total dose of 30-35 Gy. Cerebral angiographies before and after embolization were digitally compared for calculation of volume reduction and luminescence as a measure of AVM density. The mean AVM volume in 15 patients was reduced from 11.9 +/- 2.1 (1-29, median 10.0) ml to 6.5 +/- 2.0 (0.5-28, median 3) ml by embolization. The luminescence for all AVMs was significantly higher after than before embolization, indicating that all AVMs were less dense after embolization. Thirteen out of 16 patients (13/16, 81%) treated with embolization and HCSRT have so far shown obliteration of their AVMs 2-9 (median 4) years after HCSRT. Three patients experienced neurological sequele after embolization, and three patients developed radionecrosis after HCSRT. Using a new method to compare cerebral angiographies in AVMs we report reduction in density and volume after embolization. The obliteration rate of a combined treatment with embolization and HCSRT seems comparable with single fraction radiosurgery although the AVMs in our series are larger than reported in most series treated with single fraction radiosurgery. PMID- 20584479 TI - Early Disappearance of Cord Signal Changes Following Endovascular Treatment of a Spinal Dural AV Fistula. AB - SUMMARY: Spinal dural arterio venous fistulas (SDAVFs) are the commonest type of spinal vascular malformations and are encountered mostly among adult patients. Magnetic Resonance Imaging (MRI) in patients with SDAVFs demonstrates features like spinal cord swelling and signal changes. Cord signal changes are believed to be due to venous stasis.Treatment of a spinal vascular malformation may result in complete or partial resolution of MR findings with associated clinical improvement. The earliest documentation of reduction or disappearance of cord signal changes on post treatment MR images, was one month later in one series in the literature.We present and discuss disappearance of cord signal changes on MRI within 72 hours following endovascular treatment by liquid glue injection in a patient with SDAVF. PMID- 20584480 TI - Simultaneous Bilateral Vertebral Artery 3D Rotational Angiography. Technical Report of Two Cases. AB - SUMMARY: We describe the first reported use of simultaneous bilateral vertebral artery rotational angiography to visualize an aneurysm. Images acquired from 3D rotational angiography with a single vertebral injection provided insufficient anatomic detail in two cases with vertebrobasilar junction aneurysms associated with fenestration. Therefore, simultaneous bilateral vertebral artery 3D rotational runs were performed. Anatomic detail was superior with the simultaneous injection and this allowed for the appropriate plan of care to be instituted. In the rare cases of vertebrobasilar junction aneurysm associated with fenestration, simultaneous bilateral vertebral artery 3D rotational angiography may provide the most useful anatomic detail when evaluating a patient for possible endovascular intervention. PMID- 20584481 TI - Cerebral Arteriovenous Malformation Embolized through Persistent Primitive Hypoglossal Artery: A Case Report. AB - SUMMARY: Carotid-vertebral anastomoses are commonly detected as incidental findings. But sometimes these channels are important for the clinical condition of the patient. Here a case of right thalamo- capsular arteriovenous malformation is described where a persistent primitive hypoglossal artery was the only route for embolization of the arteriovenous malformation. PMID- 20584482 TI - Aneurysm of persistent primitive hypoglossal artery occluded with guglielmi detachable coils. AB - SUMMARY: The persistent primitive hypoglossal artery is rare remnant of one of the four embryonal carotid-basilar anastomoses. It is present in 0.02- 0.26% of all cerebral angiogram. 14 cases of PHA aneurysms have been reportede in the literature and as far as we know no case in which endovascular embolization was used as a treatment. We present a case with subarachnoid haemorrhage due to aneurysm of persistent primitive hypoglossal artery. The aneurysm was successfully occluded with Guglielmi detachable coils. The SAH resolved and recovery was uneventful. PMID- 20584483 TI - Multiple intracranial aneurysms as delayed complication of atrial myxoma. Case report and literature review. AB - SUMMARY: We report a case of multiple intracranial aneurysms as delayed complication of atrial myxoma.We reviewed the literature of intracranial myxomal aneurysms, and trying to find reasonable therapy methods, but got the conclusion that neurosurgery and interventional treatment were not helpful, chemotherapy and radiotherapy maybe useful in the treatment of such cases. PMID- 20584484 TI - Temporary hidden aneurysms during pregnancy. A case report. AB - SUMMARY: There are a number of reports on cerebral aneurysmal ruptures during pregnancy. Although the cerebral aneurysmal rupture is quite rare during pregnancy, it leads to a high maternal mortality; which gives rise to a clinical significance. We have encountered a number of multiple cerebral aneurysms during pregnancy, and the ruptured cases were successfully treated with the coiling procedures. The coiling is found to be a good treatment method for ruptured aneurysms during pregnancy. The cerebral angiogram is the gold standard diagnostic method for detecting cerebral aneurysms. However, 1.8-20% of the cases are reported to be false negative in initial angiography, and only up to 20% can be diagnosed even with the additional angiographies.A special attention for a hidden aneurysm should also be required while managing the patients. PMID- 20584485 TI - High-flow traumatic carotico-jugular fistula manifesting as venous hypertensive encephalopathy. A case report. AB - SUMMARY: We report the clinical and angiographic findings in a patient who presented with venous hypertensive encephalopathy secondary to a traumatic carotico-jugular fistula. Endovascular entrapment of the fistula by occluding the common carotid artery and internal jugular vein at the base of the skull resulted in near total improvement of the patient's neurological status. PMID- 20584486 TI - Adjunct Use of a Self-expanding Stent for Treatment of Intracranial Stenosis. A Case Report. AB - SUMMARY: We present a case of a patient who received adjunct treatment with a self-expanding stent after balloon dilatation of a symptomatic stenosis of the carotid siphon. After predilatation, complementary angioplasty with a balloon expandable stent was abolished due to lack of compliance of the delivery system. Since the vascular anatomy allows for the passage of balloon systems only, the stenosis was further dilated and a self-expanding stent was delivered to avoid the risk of complications related to dissection and vessel recoil. However, problem of in-stent stenosis remains at the longterm follow-up period. PMID- 20584487 TI - Intracranial mechanical recanalization and fibrinolysis using a single hyperglide balloon microcatheter. Technical note. AB - SUMMARY: Endovascular treatment of acute blockage of the middle cerebral artery may require a combination of mechanical recanalization and chemical fibrinolysis. Using a single microcatheter to perform both techniques helps shorten procedure time. PMID- 20584488 TI - Transvenous Treatment of a Dural Arteriovenous Fistula of the Transverse Sinus by Embolization with Platinum Coils and Onyx HD 500+. AB - SUMMARY: We report the endovascular treatment of a symptomatic dural arteriovenous fistula in a 61- year-old male patient. The medial portion of the fistula was occluded with detachable platinum coils during an initial intervention using a transvenous approach. Due to persistence of the symptoms in a second intervention eight months later the fistula was completely occluded by the transvenous introduction of a liquid embolic agent (Onyx 500+). The liquid embolic agent was introduced under protection by the temporary balloon occlusion of the fistula's venous drainage. After the procedure, the patient was treated for three months with 75 mg clopidogrel (Plavix(R)) and with 100 mg acetylsalicylic acid (ASS(R)). A few days after the intervention, the patient was discharged without any neurological deficit and in good clinical condition. The follow- up examination six months later neither detected a recurrence of the dural arteriovenous fistula in the angiogram nor any neurological symptoms. PMID- 20584489 TI - Application of the liquid coil as an embolic material for arteriovenous malformations. AB - SUMMARY: The purpose of this paper is to clarify advantages and disadvantages of platinum liquid coils as an embolic material for AVMs. During the last eight years, 50 endovascular procedures using liquid coils were conducted in our institute for 19 cases with AVMs, 15 of which were located in the eloquent area. All but one presented with haemorrhage, the exception demonstrating repeated ischemic symptoms. Only liquid coils were used as the embolic material to obliterate the nidus and feeders. In ten of the 15 patients with AVMs located in the eloquent area and one case rejecting surgery, liquid coil embolization was applied one to 11 times (average 3.5 times) to achieve decrease in size and this was then followed by radiosurgery. The remaining eight AVM patients underwent total removal after liquid coil embolization. No complications were encountered during the peri-embolization period. In all cases, the purpose of embolization was to diminish the size to facilitate radiosurgery and decrease bleeding during surgery. The liquid coil has advantages as a material for embolization of AVMs; it is non-toxic and bioinart material; it seldom occludes normal minute vascular channels; when it used in a nidus, it seldom to migrates in the venous direction, and it has good radio-opacity and offers good marking for surgery. Appropriate applications include preoperative embolization or pre-radiosurgical embolization of AVMs, especially when staged embolizations are performed to reduce risk of perfusion pressure breakthrough in patients which are large or located in the eloquent area. PMID- 20584490 TI - Anatomic variations of the superficial middle cerebral vein: embryologic aspects of the regressed embryonic tentorial sinus. AB - SUMMARY: The embryonic tentorial sinus usually regressses during postnatal development, but its typical prenatal drainage patterns and intradural anastomoses can be depicted as various developmental phenotypic representations. Here, we tried to clarify the variant types of the superficial middle cerebral vein (SMCV) associated with the embryonic tentorial sinus. Total 41 patients and 82 hemispheres were included in this study. CT angiography was performed in all patients as screening for cerebrovascular disease or other intracranial disorders. A separate workstation and 3D software were used to evaluate the cranial venous systems with 3D volume rendering techniques, thin-slice MIP images, and MPR techniques for the analysis of its complicated angioarchitecture. Variations of the SMCV were classified according to the developmental alterations of the embryonic tentorial sinus, including sphenoparietal sinus (cranial remnant of tentorial sinus), basal sinus (floor of middle cranial fossa), petrosal and caudal remnant of the tentorial sinus. Secondary intradural anastomoses of cavernous and superior petrosal sinuses were also evaluated for the efferent pathways. The most frequent type of remnant tentorial sinus, sphenoparietal sinus was present in 49% (40/82) of hemispheres examined. Other regressed patterns of embryonic tentorial sinus were also identified in 38% (31/82): nine caudal remnant type around the transverse sinus, 12 petrosal type, one basal type, five unclassified cases, and mixed type were found in four cases. Secondary intradural cavernous sinus anastomosis was seen in 44% (36/82), however the most prevalent pattern was no anastomosis (46/82) with cavernous sinus. Only one case of superior petrosal sinus anastomosis was found in this series associated with basal sinus type. Anatomic variations of SMCV can be clearly demonstrated with embryologic aspects of the tentorial sinus according to its developmental regression and postnatal secondary adaptations of cerebral venous drainage. PMID- 20584491 TI - Anatomic variations of the deep cerebral veins,tributaries of Basal vein of rosenthal: embryologic aspects of the regressed embryonic tentorial sinus. AB - SUMMARY: The embryonic tentorial sinus regresses at the 60-80 mm embryologic stage and most of the deep venous channels constitute the basal vein of Rosenthal (BVR). Persisting remnants of the embryonic tentorial sinus can be seen in the adult configuration of the BVR.We tried to explain the anatomic representations of the BVR associated with the remnant embryonic tentorial sinus. A total 41 patients and 82 hemispheres were included in this study. CT angiography was performed in all patients as screening for cerebrovascular disease or other intracranial disorders. A separate workstation and 3D software were used to evaluate the cranial deep venous systems with 3D volume rendering techniques, thin-slice MIP images, and MPR techniques for the analysis of complicated angioarchitecture. Variations of the BVR were classified according to the developmental alterations of efferent pathways into four groups: telencephalic group (A) including tributaries of the uncal vein, inferior frontal vein, anterior communicating vein, and inferior striatal vein; diencephalic group (B) of the interior ventricular vein and peduncular vein; tegmental bridging group (C) of the longitudinal LMV anastomosis; tectal group (D) of the superior vermian vein and internal occipital vein in relation to the Galenic connection. The BVR constituted from the embryonic tentorial sinus was also assessed and the developmental aspects reviewed. Remnant embryonic tentorial sinus was visualized in 12% (10/82) of hemispheres, all of them invariably connected with the telencephalic (A) and diencephalic (B) groups. Most of those connections (9/10) to basal venous tributaries originated from the medial tentorial sinus except one case from the lateral tentorial sinus. No Galenic connections of the BVR were identified in 10% (8/82). Various tributaries of the BVR were classified as: Telencephalic group (A) 43% (35/82), Diencephalic group (B) 35% (29/82), Bridging group (C) 11% (9/82), and Tectal group (D) 6% (5/82). Four cases (5%) were unclassified and revealed only small basal tributaries of the BVR without connection to the great vein of Galen. Anatomic variations of the BVR connected with persistent embryonic tentorial sinus could often be demonstrated in adult configurations considering the embryologic aspects of developmental regression and secondary cerebral venous adaptations. PMID- 20584492 TI - Initial experience with intracranial stent-graft use. Technical notes. AB - SUMMARY: We describe our initial experience with the placement of two premounted balloon expandable intracranial Jostent stent-grafts within the intracavernous internal carotid artery for the treatment of a symptomatic large intracavernous aneurysm in one case and a post-traumatic caroticocavernous fistula in the second. Among the initial technical complications we encountered were stent-graft migration and rapidly progressive intragraft thrombosis, with delayed sealing of the stent-graft coverings and exclusion of the pathologies relating to the use of abciximab in both cases. Despite these initial problems both cases had excellent short-term clinical outcomes with angiographic exclusion of both lesions by day three and good clinical and angiographic outcomes at one and two months respectively. PMID- 20584493 TI - Complication analysis of 469 brain arteriovenous malformations treated with N butyl cyanoacrylate. AB - SUMMARY: We independently assessed the frequency, severity and determinants of neurological deficits after endovascular embolization with NBCA of brain arteriovenous malformations (BAVMs) to have a better basis for making treatment decisions. All the charts of 469 BAVMs patients who underwent embolization with NBCA were reviewed. We analyzed the complications and their relation to angiographic features. The 469 patients were treated with 1108 endovascular procedures. Each met one to eight times, average 2.3 times. Eleven patients showed treatment-related complications, including four haemorrhagic and seven ischemic complications. Of these 11 cases, two died, two had persistent disabling deficits, and another seven suffered transient neurological deficits. Our finding suggests a low rate of disabling treatment complications for embolization of brain AVMs with NBCA in this center. The management of AVM patients who have high risk of embolization therapy should be treated by special strategy. PMID- 20584494 TI - Percutaneous retrieval of intravascular broken catheter fragments. A novel technique using a balloon. AB - SUMMARY: We describe a novel technique to retrieve broken catheter fragments from the vascular tree at difficult locations using a balloon. A coronary balloon can be taken over a microwire into the catheter fragment to hold it after inflation of the balloon and then the whole assembly can be gradually taken out. We used this novel technique successfully in three patients where the snare failed to retrieve the broken catheter fragment from vascular tree. PMID- 20584495 TI - The dual catheter technique for coiling of wide-necked cerebral aneurysms. An under-reported method. AB - SUMMARY: Aneurysms with wide necks can be difficult to manage due to inability to contain the coil mass within the lesion. When standard devices will not suffice the use of two catheters delivering coils simultaneously into the aneurysm can often provide excellent results in terms of aneurysm obliteration. We report two cases of wide-necked aneurysms coiled successfully using the dual catheter technique. Both aneurysms were successfully treated using the dual catheter technique with coil retention within the aneurysm fundus and excellent flow throngh the afferent and efferent vessels. The dual catheter technique is an under-reported method for treating wide-necked aneurysms. Successful performance, however, relies upon considerations of coil type and delivery, coil deployment, catheter removal, and anticoagulation therapy. PMID- 20584496 TI - Spinal epidural haemangioma associated with extensive gastrointestinal haemangiomas. A case report. AB - SUMMARY: A case of spinal epidural cavernous haemangioma associated with gastrointestinal haemangiomas is discussed. The patient was a young Chinese female presenting with chronic lower back pain. She had a history of extensive gastric and small bowel haemangiomas. Lumbar spine MRI showed a heterogeneously enhancing epidural mass infiltrating the paravertebral muscles. Open biopsy confirmed an epidural cavernous haemangioma. To our knowledge, an association between spinal epidural cavernous haemangiomas and gastrointestinal haemangiomas has not been reported. PMID- 20584497 TI - Spontaneous Thrombosis of Significant Aneurysm Recanalization in the Long Term Follow-up of Coiled Aneurysms: Observation in Two Cases. AB - SUMMARY: Endovascular treatment of cerebral aneurysms with detachable coils has now been proved to be a superior alternative to open microsurgery in terms of survival free of disability at one year according to the recently published large randomized International Subaracnoid Aneurysm Trial (ISAT). However, aneurysm recanalization secondary to coil compaction is still the main problem of this technique observed in the follow-up period but treatment strategies for these regrowths are not yet well established. We present two interesting cases in which we observed a significant aneurysm recanalization at six month control angiography that was found to be spontaneously thrombosed in the late follow-up angiograms at the second and fifth years consecutively. PMID- 20584498 TI - Cerebral vasospasm and intracerebral haemorrhage in a case of pregnancy-related thrombotic thrombocytopoenic purpura/haemolytic uraemic syndrome. AB - SUMMARY: We report a case of a woman with pregnancyrelated thrombotic thrombocytopoenic purpura/haemolytic uraemic syndrome (TTP/HUS) who developed cerebral vasospasm similar to that seen in the other pregnancy-related thrombotic microangiopathic syndromes of eclampsia and HELLP syndrome. A further complication in this case was the development of a focal intracerebral haemorrhage necessitating surgical removal. Despite a successful evacuation of the haematoma and several plasma exchange treatments she developed recurrent haemolysis and thrombocytopoenia with an eventual fatal outcome due to severe pulmonary and gastrointestinal haemorrhage. PMID- 20584499 TI - Definitive embolization of meningiomas. A review. AB - SUMMARY: This review examines the possible role for definitive embolization as a primary therapy for intracranial meningiomas. Surgery or radiosurgery are currently considered the standard of care for most benign meningiomas. However, each of these carries substantial risks. The perioperative mortality for surgical resection, as reported in large series, is between 3.7-9.4%; these studies report a similarly high rate of new neurological deficits following surgery. The rate of complications from radiosurgery is reported between 2-16% and it may take months to years before improvement in symptoms occurs following this therapy. There are a few reports of treating meningiomas by embolization without subsequent surgery. While these studies include small numbers of patients and have limited follow-up, the initial results are very promising. Given the risks and limitations of surgery and radiosurgery, prospective trials are now needed to determine the safety and efficacy of definitive embolization. PMID- 20584500 TI - Contribution of renal tubule epithelial cells in the innate immune response during renal bacterial infections and ischemia-reperfusion injury. AB - The epithelial cells that line the renal tubule are sometimes severely injured in the course of inflammatory kidney diseases. These renal tubule epithelial cells (RTECs) express some of the Toll-like receptors (TLRs) of the innate immune system. A number of studies have implicated RTECs, together with bone marrow derived cells, in triggering an innate immune response to bacterial infection and/or ischemic stress. RTECs expressing TLR4, which recognizes lipopolysaccharide (LPS), contribute to defending the host against ascending urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPECs). Activation of TLR2 and TLR4 signaling by endogenous damage-associated molecular patterns controls the inflammatory responses of RTECs and cell apoptosis in kidneys subjected to ischemia/reperfusion (I/R) injury. This review will consider some recent advances in understanding of the role of RTECs in inducing the innate immune response in experimental models of ascending UTIs and renal I/R injury. Arginine vasopressin, which regulates renal water absorption, has been shown to act as a potent modulator of the innate response in collecting duct cells, a preferred intrarenal site for UPEC adhesion. The activation of the mitogen associated protein kinase ERK1/2 in post-hypoxic RTECs has also been shown to be selectively regulated by TLR2 via the serine-threonine protein phosphatase 5, which is associated with the endoplasmic reticulum resident heat shock protein, gp96, which acts as a master chaperone of TLRs. These findings provide further support for the concept that RTECs are actively involved in triggering the innate immune response, at least in the context of ascending UTIs and I/R injury. PMID- 20584501 TI - Using biomechanics to improve the surgical technique for internal fixation of intracapsular femoral neck fractures. AB - Despite advances in science and technology, the success rate for the treatment of displaced intracapsular femoral neck fractures in high-energy injuries remains disappointing. The blood supply system in the femoral head of humans does not favor recovery from these fractures. Once these fractures occur, osteonecrosis and nonunion rates may be as high as 30%, even if the newest technique is used. There are some surgical techniques used to supplement internal fixation to reestablish the blood supply in the femoral head, but none have been evidently successful. After analysis of related studies, the author concludes that immediate surgical treatment using improved techniques incorporating the principles of biomechanics can improve the success rate of treatment of these fractures. Using these principles, the fracture site can achieve sufficient stability. Consequently, the blood supply in the femoral head and neck can be reestablished earlier and loss of reduction of fragments during treatment can be minimized. Thus, the chance of full recovery from these complicated fractures can be maximized. In this study, the biomechanical characteristics of these fractures and the principles associated with the surgical techniques used for treating them are reviewed and clarified. Finally, a surgical technique which is ideal from the author's viewpoint is presented. The author believes that the recommended surgical technique may become the best method for treating these complicated fractures. PMID- 20584502 TI - Anti-osteoporotic activity of the petroleum ether extract of Cissus quadrangularis Linn. in ovariectomized Wistar rats. AB - BACKGROUND: The plant Cissus quadrangularis (CQ) is used as an osteoprotective agent in Ayurveda, the Indian system of alternative medicine. The present study was done to validate the anti-osteoporotic role of the petroleum ether extract of CQ on ovariectomy-induced osteoporosis in rats. METHODS: Female wistar rats were divided into five groups of six rats each; (1) The Normal control (NC) group (n=6) received no surgery and no treatment, (2). The Sham control (SHAM) group (n=6) received sham surgery but no treatment, (3) the Ovariectomized (OVX) group (n=6) received an ovariectomy and normal saline treatment for 90 days, (4) the Ovariectomized+raloxifene (OVX+RAL) group (n=6) received an ovariectomy and treatment with raloxifene, a known anti-osteoporotic agent for 90 days commencing from 22nd post ovariectomy day and (5) the Ovariectomy+Cissus quadrangularis (OVX+CQ) group (n=6) received an ovariectomy, and treatmentwith the petroleum ether extract of CQ 500 mg/kg body weight daily for 90 days commencing from 22nd post ovariectomy day. At the end of the treatment period, rats in all groups were sacrificed and the right femur was used for biomechanical analysis, and the left femur for histomorphometrical analysis. RESULTS: CQ significantly increased the force required to break the femur (p<0.001) and significantly increased the thickness of both cortical (p<0.001) and trabecular bone (p<0.001). This action of CQ was comparable to the action of raloxifene. CONCLUSIONS: The petroleum ether extract of CQ stem seems to possess anti-osteoporotic activity in rats. PMID- 20584503 TI - Prevalence and clinical relevance of serum autoantibodies in patients with chronic hepatitis C. AB - BACKGROUND: Chronic hepatitis C (CHC) is frequently associated with the presence of serum autoantibodies. The prevalence and clinical relevance of serum autoantibodies in CHC patients and their influence on antiviral treatment have not been well established. METHODS: From February 1999 to July 2004, 460 consecutive adult patients with CHC were studied. Antinuclear antibody (ANA) and smooth muscle antibody (SMA) were determined by indirect immunofluorescence. The presence of these antibodies was related to patient characteristics and to the outcome of 24 weeks of therapy with interferon (IFN) alfa-2b (n=376) or pegylated IFN alfa-2b (n=84) plus ribavirin. RESULTS: The prevalence of ANA and SMA was 7.4% and 19.3%, respectively. Seropositivity for ANA and/or SMA was associated with old age and high aspartate aminotransferase (AST) levels. The rates of sustained virological response and early withdrawal of therapy were comparable between autoantibody- positive and -negative patients. None of the autoantibody positive patients experienced a flare-up of transaminase during treatment, or developed severe systemic autoimmune disease. CONCLUSION: Serum ANA and/or SMA positive HCV-infected patients are older, and have higher disease activity and severity than their negative counterparts. However, the presence of ANA or SMA did not influence the response to combination antiviral therapy, which is safe and effective in autoantibody--positive CHC patients. PMID- 20584504 TI - Early reduction for congenital dislocation of the knee within twenty-four hours of birth. AB - BACKGROUND: Congenital dislocation of the knee (CDK) is a very rare condition that comprises a spectrum of deformities from subluxation to complete dislocation. The incidence of CDK is estimated at 1 per 100,000 live births, which is 1% of the incidence of developmental dysplasia of the hip (DDH). Moreover, 40-100% of patients with CDK have additional musculoskeletal anomalies, the most common being DDH and clubfoot. In general, the diagnosis is established immediately after birth according to the position of the knee recurvatum. Treatment with conservative methods at an early stage is most likely to yield successful results. We report here successful treatment of a series of CDK patients with early reduction. METHODS: From July 1990 to June 2007, 19 patients with CDK (affecting 25 knees) were treated with early reduction. Of these, 6 knees had dislocation, and 19 had subluxation. Since 1990, treatment has been guided by a protocol that considers patient age and the severity of the condition. In patients examined within 24 hours of birth, early, direct reduction under gentle, persistent manual traction was attempted. Birth history and perinatal course were obtained from medical records. Associated musculoskeletal anomalies were observed and treated after reduction of the knee joint. A Pavlik harness was used for at least 4 months in the concomitant treatment of DDH and CDK. Knee function was graded as excellent, good, fair, or poor. Radiographs were used to assess DDH during follow-up. RESULTS: After an average follow-up duration of 4.3 years, 18 patients showed an excellent or good outcome. One patient, whose knee could not be reduced, had severe multiple anomalies and died 16 days after birth. Fifteen of the nineteen patients had associated musculoskeletal anomalies, including DDH and foot deformity. Two cases of residual hip dysplasia after Pavlik harnessapplication required an acetabular osteotomy. CONCLUSIONS: For CDK patients, early and direct closed reduction within 24 hours of birth affords outcomes graded as either excellent or good. PMID- 20584505 TI - An early predictor of the outcome of patients with ventilator-associated pneumonia. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) contributes to high mortality, prolonged intensive care unit (ICU) stay and increased costs of health care. Reports of early predictors of death in patients with VAP are rare. Our study was designed to determine early predictors of poor outcome in patients with VAP. METHODS: A total 838 patients with nosocomial lower respiratory tract infection in a tertiary medical center from January, 2004 to June, 2006 were retrospectively reviewed. Forty-two patients had VAP and were enrolled in the study. The age, sex, underlying diseases, including hypertension, diabetes mellitus, chronic obstructive pulmonary disease, end-stage renal disease, congestive heart failure/coronary artery disease, and collagen vascular disease, diagnosis at admission, Acute Physiological Assessment and Chronic Health Evaluation II score (APACHE II score), Clinical Pulmonary Infection Score (CPIS), time between intubation and ICU admission, time between intubation and development of VAP, risk factors for multi-drug resistant pathogens, time to adequate therapy, initial antibiotics regimen, bacterial cultures, mortality rate from VAP, 28-day mortality rate and in-hospital mortality rate were compared between the mortality group and non-mortality group. RESULTS: The VAP, 28-day and in-hospital mortality rates were 23.8% (10/42), 40.5% (17/42) and 50% (21/42), respectively. The APACHE II score (p=0.002) and CPIS (p=0.048) at the onset of VAP, inadequate initial antibiotics treatment (p=0.007) and concomitant bacteremia (p=0.008) were the only parameters which were significantly different between groups. The independent risk factors for VAP mortality in multivariable analysis were the APACHE II score at the onset of VAP (p=0.018), inadequate initial antibiotics treatment (p=0.032) and concomitant bacteremia (p=0.034). An APACHE II score>27 at VAP onset was an independent and early predictor of the mortality. (ROC AUC: 0.841; Sensitivity: 70%; Specificity: 90.6%; p=0.001). CONCLUSION: A high APACHE II score (>27) at VAP onset was an independent and early predictor of mortality due to VAP. PMID- 20584506 TI - Impact of comorbidity on survival for locally advanced head and neck cancer patients treated by radiotherapy or radiotherapy plus chemotherapy. AB - BACKGROUND: The aim of this study was to investigate the impact of comorbidity on survival for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 214 patients with locally advanced HNSCC, treated with radiotherapy (RT) or RT plus chemotherapy (CT) from January 2000 to December 2003, were included. Comorbidity was scored by the Charlson comorbidity index (CCI). The patient-, tumor-, and treatment-related variables were recorded and overall survival (OS) and disease specific survival (DSS) were calculated. RESULTS: Seventy-one patients (33%) had at least one comorbid condition. The most common comorbid condition was liver disease (13.6%). Higher CCI scores were not significantly correlated with exposure to smoking, alcohol, or betel quid, but were associated with older age, fewer years of education years, and no CT (p<0.05). The 3-year OS and DSS rates were, respectively, 21.9% and 24.4% for all patients; 25.9% and 26.9% for those with CCI scores of 0, 21.8% and 28.3% for scores of 1, and 3.5% and 7.5% for scores>or=2. Multivariate analysis revealed that a CCI score>or=2, stage IV disease, a RT dose<70 Gy, and no CT were significant predictors of poorer OS and DSS. CONCLUSIONS: Our data reveal the significant survival impact of comorbidity on patients with locally advanced HNSCC treated by RT or RT plus CT. PMID- 20584507 TI - Changes in consultation-liaison psychiatry in the first five years of opearation of a newly-opened hospital. AB - BACKGROUND: Many studies have addressed changes in psychiatric consultation variables, but data from newly-opened hospitals is scarce. Thus, the aim of this study was to investigate changes in consultation-liaison services in the first five years of operation of a newly-opened hospital and compare this with similar data from established hospitals. METHODS: Psychiatric consultations in the first five years of operation of a new hospital were reviewed and psychiatric variables, including reason for referral, psychiatric diagnosis, physical condition leading to hospitalization, and recommended management, were collected. RESULTS: There were 1,610 psychiatric consultations in these five years, and the overall consultation rate was 1.30% of all admissions. The rate was relatively low in the first year, especially from the surgery department, but increased and then stabilized. The reasons for most referrals did not change significantly over the 5 years. Depression was the most frequent reason for referral and the major diagnosis during the study period. Although the diagnosis of depression increased significantly over the years, depression as a reason for referral did not increase consistently. A drug prescription was the most frequent recommendation, and medications shifted to more atypical antipsychotics and newer antidepressants over the study period. CONCLUSIONS: Most variables were stable, but there were still some interesting findings. The consultation rate was lower during the first year of the study period than later. Underdetection and underrecognition of depression persisted over the 5 years. Further comprehensive postgraduate education for physicians and arrangment of timely consultations are needed. These results could offer information on psychiatric consultations to other hospitals that are going to open in the future. PMID- 20584508 TI - Preoperative serum C-reactive protein and gastric cancer; clinical-pathological correlation and prognostic significance. AB - BACKGROUND: C-reactive protein (CRP) is a widely-used systemic biomarker for inflammation. Serum CRP is elevated in many malignancies, and is also a prognostic indicator of malignant potential. However, the prognostic significance for survival from gastric cancer has not yet been clarified. We studied the clinical- pathologic association and prognostic significance of preoperative serum CRP in gastric cancer patients. METHODS: A total of 170 gastric cancer patients were included in this study. The mean age of the patients was 65.1 years (range, 29-89), and 112 were men. All gastric cancer patients had undergone gastric resection. The serum CRP levels of patients before the operation along with those from 405 healthy controls were measured by a high sensitivity CRP test. RESULTS: The 95th percentile value (=3.0 mg/L) of the serum CRP data in 405 healthy controls was set as the upper cut-off value of the normal range. Abnormally high levels of serum CRP were observed in 65 (38.2%) of our 170 patients in contrast to only 20 (4.9%) of the 405 healthy controls (p<0.001). Elevated CRP was associated with older age (p=0.009), grossly infiltrative type (p=0.001), larger tumors (p<0.001), serosal invasion (p=0.001), lymph node metastasis (p<0.001), distant metastasis (p=0.017), and lymphatic invasion (p=0.002). Overall, a higher CRP level was strongly parallel to a pathologically more advanced stage (p=0.001). The 5-yr survival rate of patients with an elevated (>3.0 mg/L) CRP was significantly worse than those without (= 2-year follow up. Severe side effects or drug abuse were not detected in this cohort. CONCLUSIONS: The long-term treatment outcome shows that stimulants are effective in adult ADHD and side effects tend to be mild. PMID- 20584518 TI - Determinants of poor dental care in patients with schizophrenia: a historical, prospective database study. AB - BACKGROUND: Oral health status is poor and a disregarded health issue among patients with schizophrenia that is associated with the risk for additional social stigmatization and potentially fatal infections. METHOD: A historical, prospective database study of dental visits, utilizing the Danish National Patient Registry, of 21,417 patients with ICD-10-diagnosed schizophrenia in the year 2006 and of 18,892 patients for the 3-year period of 2004-2006 was conducted. Multiple logistic regression analyses were used to identify risk factors for lack of dental care. RESULTS: Only 43% of patients with schizophrenia (9,263/21,417)--compared to an annual dental visit rate of 68% in the general adult Danish population (2,567,634/3,790,446)-visited the dentist within 12 months in 2006 (OR = 2.8; 95% CI, 2.7-2.9; P < .0001). Moreover, only 31% of schizophrenia patients complied with a regular annual dental check-up visit between 2004 and 2006. Nonadherence to annual dental visits was consistently predicted by substance abuse diagnosis, involuntary legal status, living in an institution, admission to a psychiatric facility for a minimum of 30 days, and male sex, whereas clozapine treatment, atypical antipsychotic treatment, at least monthly outpatient visits, and age > 50 years were associated with a lower risk for inappropriate dental care. CONCLUSIONS: Patients with schizophrenia visit dentists much less frequently than the general population in the same country. Health professionals should pay more attention to the dental health care of patients with schizophrenia, actively encourage patients to regularly visit the dentist, and establish a formal collaboration with dentists to improve the dental health aspects of this disadvantaged patient group. PMID- 20584519 TI - Trauma exposure and posttraumatic stress disorder in primary care patients: cross sectional criterion standard study. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is one of the most common but least recognized anxiety disorders in primary care. This study aimed to describe the association of PTSD and trauma exposure with somatic symptoms, psychiatric comorbidity, functional impairment, and the actual treatment of PTSD in primary care. METHOD: This cross-sectional criterion standard study included 965 consecutive primary care patients from 15 civilian primary care clinics in the United States. The Structured Clinical Interview for DSM-IV (SCID) was used to establish diagnosis of PTSD and other anxiety disorders. Somatic symptoms, depression, and anxiety were measured with the Patient Health Questionnaire (PHQ), and functional impairment was measured with the Medical Outcomes Study Short-Form General Health Survey (SF-20). The study was conducted from November 2004 to June 2005. RESULTS: PTSD was diagnosed in 83 patients (8.6%; 95% CI, 7.0% 10.5%), and trauma exposure without fulfilling DSM-IV criteria for PTSD was reported by 169 patients (17.5%; 15.2%-20.0%). With odds ratios ranging between 2.1 (95% CI, 1.2-3.6) for headache and 9.7 (3.8-24.8) for chest pain, PTSD patients had markedly elevated somatic symptom rates compared to the reference group of patients with no PTSD or trauma exposure. PTSD was significantly associated with elevated rates of psychiatric comorbidity, pain, and impaired functioning. Patients reporting trauma but no PTSD had rates of somatic symptoms, psychiatric comorbidity, and functional impairment that were intermediate between PTSD and reference group patients. Adjusting for depression substantially attenuated the association of PTSD and trauma with somatic symptoms, suggesting that depression may be an important mediator of the PTSD-somatic symptoms relationship. CONCLUSIONS: The high frequency of PTSD in primary care and its association with psychiatric comorbidity and functional impairment underscore the need to better detect and treat PTSD in primary care. Recognizing the frequent somatic presentation of PTSD and appreciating the salience of comorbid depression may be especially important in optimizing PTSD care. PMID- 20584520 TI - Persistent depressive symptoms and cognitive function in late midlife: the Whitehall II study. AB - OBJECTIVE: Depression has been widely linked to poor cognition and dementia in the elderly. However, comorbidity at older ages does not allow an assessment of the role of mental health as a risk factor for cognitive outcomes. We examined the association between depressive symptoms, measured 6 times over an 18-year period, and cognitive deficits in late midlife. METHOD: Of the 10,308 participants in the Whitehall II study, 4,271 men and women (aged 35-55 years at baseline) were followed up for 18 years, during which depressive symptoms were assessed 6 times using the General Health Questionnaire depression subscale. The follow-up was from 1985-1988 to 2002-2004. Cognition was assessed at the most recent wave (2002-2004, mean age 61 years, range 50-74 years) using 6 tests: memory, reasoning, vocabulary, 2 tests of verbal fluency, and the MMSE (Mini Mental State Examination). Cognitive deficit was defined as MMSE score <28 and performance in the worst sex-specific quintile for the other tests. RESULTS: History of depressive symptoms, once or more in the 6 times assessed, had a weak association with some of the cognitive tests. However, in analysis adjusted for sociodemographic variables, diabetes, coronary heart disease, hypertension, stroke, and antidepressant use, persistent depressive symptoms (4-6 times) were associated with cognitive deficits on all tests: memory (OR=1.91; 95% CI, 1.36 2.67), reasoning (OR=1.60; 95% CI, 1.15-2.20), vocabulary (OR=1.75; 95% CI, 1.27 2.41), phonemic fluency (OR=1.40; 95% CI, 1.00-1.94), semantic fluency (OR=1.68; 95% CI, 1.20-2.35), and the MMSE (OR=1.76; 95% CI, 1.25-2.50). CONCLUSIONS: Our data show that depressive episodes tend to persist in some individuals, and these individuals are at a greater risk of cognitive deficits in late midlife. PMID- 20584522 TI - A cohort study of the prevalence and impact of comorbid medical conditions in pediatric bipolar disorder. AB - OBJECTIVE: To identify the association between medical or psychiatric comorbidities, clinical characteristics, or course of illness/recovery in pediatric bipolar disorder (BD). METHOD: Data from the South Carolina Medicaid program covering all medical services and medication prescriptions between January 1996 and December 2005 were used to analyze the temporal onset of 12 comorbid medical or psychiatric conditions for 1,841 children and adolescents diagnosed with BD using DSM-IV-TR criteria and for a random sample of 4,500 children not treated for psychiatric disorders. The primary outcome measures were diagnostic codes and regression analyses of patterns of acute and outpatient treatment services for BD over time. RESULTS: Ten conditions examined were significantly more prevalent in the BD cohort: obesity, type 2 diabetes mellitus, endocrine disorders, migraine headaches, central nervous system (CNS) disorders/epilepsy, organic brain disorders/mental retardation, cardiovascular disorders, attention-deficit/hyperactivity disorder (ADHD), asthma, and substance abuse (P <= .01). For clinical characteristics within the BD cohort, an adolescent-onset diagnosis of BD (age >=13 years) was significantly associated with the diagnosis of preexisting obesity, hypertension, migraine, mental retardation, endocrine disorders, and substance abuse (P <= .05), whereas recurrent depressive episodes were associated with preexisting endocrine disorders and substance abuse. Preexisting ADHD, substance abuse, CNS disorders/epilepsy, cardiovascular disorders, obesity, and asthma were associated with higher overall medical and psychiatric outpatient and acute service use, but none of these comorbid disorders differentially impacted the course of illness or recovery for BD. CONCLUSIONS: Neuropsychiatric (ie, ADHD, substance abuse, CNS disorders/epilepsy) and medical (ie, obesity, asthma, cardiovascular disease) disorders temporally precede the diagnosis of early-onset BD in pediatric patients and are associated with discrete facets of illness presentation, but they do not substantially alter the clinical course of the BD over time. PMID- 20584521 TI - Are maternal depression or symptom severity associated with breastfeeding intention or outcomes? AB - OBJECTIVE: Breastfeeding confers many health benefits to mothers and infants, while depression negatively affects mothers and infants. The aims of this study were to determine relationships between (1) major depressive disorder (MDD) and depressive symptom severity during pregnancy and breastfeeding intention; (2) MDD and depressive symptom severity during pregnancy and breastfeeding initiation and status at 2 and 12 weeks; and (3) serotonin reuptake inhibitor (SRI) use and breastfeeding intention, initiation, and status at 2 and 12 weeks. METHOD: Women were followed prospectively from pregnancy through 12 weeks postpartum for infant feeding intention (breast, breast and formula, formula, and uncertain), feeding practices and MDD (Structured Clinical Interview for DSM-IV Disorders), and depressive symptom severity (Hamilton Depression Rating Scale). Bivariate analyses and multivariable regression modeling were conducted. The study was conducted from July 2004 to September 2007. RESULTS: Study participants (intention n = 168, initiation n = 151, 2 weeks n = 137, 12 weeks n=103) were well educated (63% college degrees), older (49% >= or = 31 years), and predominantly white (77%). At enrollment, 23% had MDD, 21% had significant depressive symptoms, and 16% were taking an SRI. Neither MDD nor depressive symptom severity in pregnancy was related to breastfeeding intention, initiation or duration at 2 and 12 weeks. Intention to exclusively breastfeed was the most significant predictor of breastfeeding initiation and duration. SRI use in pregnancy was negatively associated with breastfeeding intention. SRI use at 2 weeks was negatively associated with 12-week breastfeeding status. CONCLUSION: Pregnancy is the optimal time to intervene to increase breastfeeding rates. Future research should identify strategies to overcome breastfeeding barriers posed by SRI use. PMID- 20584523 TI - Exploration of the resilience construct in posttraumatic stress disorder severity and functional correlates in military combat veterans who have served since September 11, 2001. AB - OBJECTIVE: This study evaluated the relationship between resilience and psychological functioning in military veterans deployed to a region of military conflict in support of Operation Enduring Freedom or Operation Iraqi Freedom. METHOD: 497 military veterans completed a structured psychiatric interview and questionnaires measuring psychological symptoms, resiliency, and trauma exposure. The study had 2 primary aims: (1) to examine whether the association between trauma exposure and PTSD was moderated by resilience and (2) to examine whether resilience was uniquely associated with functional outcomes after accounting for PTSD. Measures included the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (for PTSD diagnosis), the Connor-Davidson Resilience Scale, and the Traumatic Life Events Questionnaire. Data were collected between June 2005 and February 2009. RESULTS: Evaluating the association of resilience and trauma exposure with PTSD revealed main effects for combat exposure, lifetime trauma exposure, and resilience. Additionally, there was a significant (P < .05) interaction between combat exposure and resilience such that higher levels of resilience were particularly protective among individuals with high combat exposure. After controlling for age, gender, minority status, trauma exposure, and PTSD diagnosis, resilience was uniquely associated with decreased suicidality, reduced alcohol problems, lower depressive symptom severity, and fewer current health complaints and lifetime and past-year medical problems. CONCLUSIONS: These results suggest that resilience is a construct that may play a unique role in the occurrence of PTSD and severity of other functional correlates among deployed veterans. Future studies in this area would benefit from a prospective design, the evaluation of other possible protective processes (e.g., social support), and specific examination of particular aspects of resilience and how resilience may be increased. PMID- 20584524 TI - A systematic review of aripiprazole--dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. AB - OBJECTIVE: To evaluate relationships between aripiprazole dose, plasma level, pharmacologic activity, and clinical outcome in order to evaluate the potential for therapeutic drug monitoring. DATA SOURCES: In August 2008, we searched Embase, MEDLINE, and PubMed databases using the keywords aripiprazole, plasma levels, plasma concentration, and therapeutic drug monitoring. STUDY SELECTION: Twenty-one reports were retrieved. Eight studies investigating the relationship between blood concentrations of aripiprazole and dose, dopamine D(2)/D(3) occupancy, and/or outcome and adverse effects were then selected. DATA EXTRACTION: All data concerning plasma or serum concentrations of aripiprazole were included if concentrations were reported in relation to a dose, dopamine occupancy, or clinical outcome. Those reports solely investigating drug interactions were not included. DATA SYNTHESIS: A strong correlation exists between aripiprazole dose and plasma concentration. Positron emission tomography analyses suggest that there are significant relationships between dopamine receptor occupancy and both aripiprazole dose and blood concentration. Dopamine receptor occupancy appears to reach a plateau at doses above 10 mg, supporting the observation found in dose-response studies that 10 mg/d is the optimal dose for aripiprazole. CONCLUSIONS: The dose range for aripiprazole is well defined, and it reliably predicts plasma level, dopamine receptor occupancy, and clinical response. Plasma level variation appears to have minimal impact on clinical response, but it may predict some adverse effects. A putative target plasma level range of between 150 and 210 ng/mL is suggested. Therapeutic drug monitoring has limited value in the clinical use of aripiprazole, but it may be useful in assuring adherence and optimizing response in individuals. PMID- 20584525 TI - The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. AB - OBJECTIVE: To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode (MDE). METHOD: Inclusive, double-blind, randomized, controlled, 8-week, parallel group trial, conducted October 17, 2005 through January 30, 2009 in 8 Canadian academic and psychiatric clinics. Adult outpatients (N = 432) with MDE (Mini International Neuropsychiatric Interview, version 5.0.0, criteria) lasting at least 4 weeks, including 40.3% taking antidepressants at baseline, were randomly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid (EPA) and 150 mg/d of docosahexaenoic acid (DHA) or matched sunflower oil placebo (2% fish oil). The primary outcome was the self-report Inventory of Depressive Symptomatology (IDS SR(30)); the secondary outcome was the clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The adjusted mean difference between treatment and placebo was 1.32 points (95% CI, -0.20 to 2.84; P = .088) on the IDS-SR(30) and 0.97 points (95% CI, -0.012 to 1.95; P = .053) on the MADRS. Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group (P = .035). For patients without comorbid anxiety disorders (n = 204), omega-3 supplementation was superior to placebo, with an adjusted mean difference of 3.17 points on the IDS-SR(30) (95% CI, 0.89 to 5.45; P = .007) and 1.93 points (95% CI, 0.50 to 3.36; P = .008) on the MADRS. CONCLUSIONS: In this heterogeneous sample of patients with MDE, there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms. However, there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders. TRIAL REGISTRATION: controlled-trials.com Identifier: ISRCTN47431149. PMID- 20584526 TI - The spectrum of anxiety disorders in the medically ill. AB - OBJECTIVE: The purpose of this cross-sectional study was to assess the prevalence and characteristics of anxiety disorders in the medically ill. METHOD: A sample of 1,660 medical patients was recruited from different medical settings in different periods from 1996 to 2007. All patients underwent detailed semistructured interviews with the Structured Clinical Interview for DSM-IV (SCID) and the Structured Interview for Diagnostic Criteria for Psychosomatic Research (DCPR). RESULTS: Generalized anxiety disorder was the most frequent anxiety disturbance (10.3%) and was associated with DCPR somatization syndromes, Type A behavior, and irritable mood. Panic disorder with agoraphobia and agoraphobia without history of panic disorder had almost identical prevalence (about 4.5%), but differed in some patterns of somatization. Agoraphobia without panic attacks was related to illness denial, persistent somatization, anniversary reactions, and demoralization. Much lower prevalence rates were reported for social phobia and obsessive-compulsive disorder. CONCLUSIONS: The findings indicate that anxiety disorders are common in the setting of medical disease and are associated with several types of psychosomatic presentations. The links between agoraphobia without history of panic disorder and illness denial may provide an explanation for some discrepancies that have occurred in the literature as to the prevalence of agoraphobia in clinical samples compared to epidemiologic studies. PMID- 20584527 TI - InCl(3)-catalyzed asymmetric aza-Friedel-Crafts reaction of indoles with imines generated from O-pivaloylated beta-D-galactosylamine. AB - The highly diastereoselective InCl(3)-catalyzed aza-Friedel-Crafts reaction of substituted indoles with aldimines generated from Kunz's amine was studied. The reaction afforded the desired product in good to high yields with up to >19:1 diastereoselective ratios. The O-pivaloylated beta-D-galactosyl moiety could not be cleaved under the traditional acidic conditions. It was removed successfully after unmasking of the O-pivaloyl groups using MeOH/NaOMe and treatment with HOAc/H(2)O subsequently, to yield the 3-indolyl aryl methanamine derivatives in high optical purity. PMID- 20584528 TI - Towards a modular synthesis of well-defined chitooligosaccharides: synthesis of the four chitodisaccharides. AB - The total chemical synthesis of the four well-defined chitodisaccharides is described using N-trichloroacetyl (TCA) and N-benzyloxycarbonyl (Z) as C-2 protecting groups for acetamido and free amino groups, respectively. The synthesis is carried out according to a strategy that paves way to the elaboration of various homo- and hetero-chitooligosaccharides, with perfect control of the number and the position of GlcN and GlcNAc units along the oligomer chain. PMID- 20584529 TI - Self-assembly behavior of hematite nanoparticles with controllable anisotropic morphology. AB - In this work, complex structures such as long chain, "semi-flexible" chain, "threefold junction" and network were formed by self-assembly of colloidal hematite nanoparticles. Morphology of these colloidal nanoparticles used as building blocks transformed from truncated rhombohedra, hexagon to pseudo-hexagon by altering reaction time and surfactants. By further observation using HRTEM, these nanoparticles were confirmed to grow along the c-axis. It was found that the molecular structures of surfactants make great influence on the transformation of bonding modes between carboxyl and iron atom on the surface. Then crystal growth rate was changed. It led to two opposite growth trends along the c-axis. More interestingly, the chains formed by these colloidal nanoparticles were also assembled along the c-axis. Meanwhile, configuration diversity seemed related to the morphological anisotropy along the c-axis. It was believed that two main forces between the nanoparticles were responsible for the various configurations, magnetic dipole-dipole and exchange-coupling interaction. The morphological anisotropy was considered to play a key role in the coordination of the two interactions which led to different complex structures by self-assembly. Discussion was taken to explain the formation of these interesting configurations. PMID- 20584530 TI - Study of solvent adsorption on chemically bonded stationary phases by microcalorimetry and liquid chromatography. AB - A detailed, molecular-level description of the sorption mechanism in reversed phase liquid chromatography is of great interest to analytical chemists. For this purpose, solvent adsorption in the octadecyl stationary bonded phase was investigated. Preferential adsorption of solvents from an acetonitrile-water and methanol-water mobile phase was measured on a series of non-end-capped octadecyl bonded phases with different coverage densities of bonded ligands using the minor disturbance method. For a comparison, a microcalorimetric study of organic solvent adsorption on the stationary phase was executed. The results from the excess isotherm measurement agree well with the experimental measurement of the heat of immersion of the bonded stationary phases by the test solvents. The microcalorimetric measurement is another method for determination of solvation processes of the stationary phases. Changes of the heat of immersion provide information about the surface accessibility for interaction with solvent molecules. The increase of the stationary phase coverage density reduces the free space between bonded chains and penetration of solvent between organic chains. PMID- 20584531 TI - Fibrodysplasia ossificans progressiva: early diagnosis is critical yet challenging. PMID- 20584532 TI - Assessing portal fibrosis in parenteral nutrition-dependent patients treated with omega-3 fatty acid lipid emulsion. PMID- 20584533 TI - Standard versus bicaval techniques for orthotopic heart transplantation: an analysis of the United Network for Organ Sharing database. AB - OBJECTIVE: Most studies of anastomotic technique have been underpowered to detect subtle differences in survival. We analyzed the United Network for Organ Sharing database for trends in use and outcomes after either bicaval or traditional (biatrial) anastomoses for heart implantation. METHODS: Review of United Network for Organ Sharing data identified 20,999 recipients of heart transplants from 1997 to 2007. Patients were stratified based on the technique of atrial anastomosis: standard biatrial (atrial group, n = 11,919, 59.3%), bicaval (caval group, n = 7661, 38.1%), or total orthotopic (total group, n = 519, 2.6%). RESULTS: The use of the bicaval anastomosis is increasing, but many transplantations continue to use a biatrial anastomosis (1997, 0.2% vs 97.6%; 2007, 62.0% vs 34.7%; P < .0001). Atrial group patients required permanent pacemaker implantation more often (odds ratio, 2.6; 95% confidence interval, 2.2 3.1). Caval group patients had a significant advantage in 30-day mortality (odds ratio, 0.83; 95% confidence interval, 0.75-0.93), and Cox regression analysis confirmed the decreased long-term survival in the atrial group (hazard ratio, 1.11; 95% confidence interval, 1.04-1.19). CONCLUSIONS: Heart transplantations performed with bicaval anastomoses require postoperative permanent pacemaker implantation at lower frequency and have a small but significant survival advantage compared with biatrial anastomoses. We recommend that except where technical considerations require a biatrial technique, bicaval anastomoses should be performed for heart transplantation. PMID- 20584534 TI - An improved technique for aortic anastomosis: graft telescopic inversion. PMID- 20584535 TI - Thoracic metastasectomy for adoptive immunotherapy of melanoma: a single institution experience. AB - OBJECTIVES: Although refractory to chemotherapy, metastatic melanoma may respond to adoptive immunotherapy. As novel treatments evolve, surgeons may be asked to perform metastasectomy not only for palliation or potential cure but also for isolation of tumor-infiltrating lymphocytes. This study was undertaken to examine outcomes of patients with melanoma undergoing thoracic metastasectomy in preparation for investigational immunotherapy. METHODS: A retrospective review identified 107 consecutive patients who underwent 116 thoracic metastasectomy procedures from April 1998 to July 2009. Indications for surgical intervention included procurement of tumor-infiltrating lymphocytes, rendering of patients to no evaluable disease status, palliation, and diagnosis. Response Evaluation Criteria in Solid Tumors criteria were used to assess tumor response. RESULTS: Thoracotomy, lobectomy, and video-assisted thoracoscopic surgery with nonanatomic resection were the most common procedures. Major complications included 1 death and 1 coagulopathy-induced hemothorax. Seventeen patients were rendered to no evaluable disease status. Virtually all patients with residual disease had tumor specimens cultured for tumor-infiltrating lymphocytes; approximately 70% of tumor infiltrating lymphocyte cultures exhibited antitumor reactivity. Of the 91 patients with residual or recurrent disease, 24 (26%) underwent adoptive cell transfer of tumor-infiltrating lymphocytes, of whom 7 exhibited objective responses (29% response rate and 8% based on intent to treat). Rapid disease progression precluded tumor-infiltrating lymphocyte therapy in most cases. Actuarial 1- and 5-year survival rates for patients rendered to no evaluable disease status or receiving or not receiving tumor-infiltrating lymphocytes were 93% and 76%, 64% and 33%, and 43% and 0%, respectively. CONCLUSIONS: Relatively few patients currently having thoracic metastasectomy undergo adoptive cell transfer. Continued refinement of tumor-infiltrating lymphocyte expansion protocols and improved patient selection might increase the number of patients with melanoma benefiting from these interventions. PMID- 20584536 TI - Treatment of fusiform ascending aortic aneurysms: a comparative study with 2 options. AB - OBJECTIVE: Ascending aortic replacement and reinforced reduction aortoplasty are 2 optional procedures for the treatment of fusiform ascending aneurysms. This study was designed to compare the early and late results of these 2 options. METHODS: Between January 2000 and January 2008, 71 patients with fusiform ascending aortic aneurysms and aortic valve disease underwent reinforced reduction aortoplasty associated with aortic valve replacement (RRA group, n = 32) or ascending aortic replacement combined with aortic valve replacement (AAR group, n = 39). Patients requiring other concomitant cardiac procedures were excluded. Perioperative events and late results were compared. RESULTS: The variables of the 2 groups were similar, except age and preoperative diameter of the ascending aorta. Despite the nearly identical perioperative morbidity in the 2 groups, mean cardiopulmonary bypass time and aortic crossclamping time were shorter in the RRA group. The follow-up period was between 1 and 8 years (mean, 3 years and 4 months). The 5-year survival rate was 90.7% +/- 6.4% versus 87.0% +/- 6.3%, respectively. Although there was a significant increase in aortic sinus diameters in the AAR group, all aortic sinus diameters were within the acceptable range. There was no increase in proximal aortic arch diameters in the 2 groups. CONCLUSIONS: For the treatment of fusiform ascending aortic aneurysms, both procedures can result in favorable and comparable late results in appropriate patients. Furthermore, reinforced reduction aortoplasty should be encouraged more because of its significant operative simplicity and safety if only the quality of the aortic wall is acceptable. PMID- 20584537 TI - Atrioventricular valve repair in patients with functional single ventricle. AB - OBJECTIVE: We aimed to evaluate surgical repair of atrioventricular valve regurgitation in patients with functional single ventricle. METHODS: The medical records of 65 consecutive patients with functional single ventricle who underwent atrioventricular valve repair between January 1999 and October 2008 were reviewed retrospectively. Their characteristics were as follows: median age, 9.5 months; median weight, 6.0 kg; atrial isomerism, 31 patients; and hypoplastic left heart syndrome, 12 patients. Regurgitation was repaired at the palliative, Glenn, and Fontan stage in 21, 29, and 15 patients, respectively. RESULTS: The overall survival was 79% and 70% at 1 and 5 years, respectively. The risk factors for mortality were age less than 3 months (P < .001), body weight less than 4 kg (P < .001), hypoplastic left heart syndrome (P = .001), concomitant Norwood (P < .001), and the palliative stage (P = .004) on the univariate analysis, and body weight less than 4 kg (P = .010, hazard ratio, 9.8; 95% confidence interval, 1.7 55.6) on the multivariate analysis. Twenty patients underwent reoperation (repairs in 15; replacements in 5), and freedom from reoperation at 1 and 5 years was 69% and 57%, respectively. Concomitant systemic-to-pulmonary shunt (P = .040) was a risk factor for reoperation on the univariate analysis. Of the 48 survivors, 38 underwent Fontan completion, 7 underwent the Glenn procedure, and 3 are awaiting the Glenn procedure. CONCLUSIONS: The midterm results of atrioventricular valve repair in patients with functional single ventricle were favorable; however, young and small patients, especially those with hypoplastic left heart syndrome, still had poor outcomes. PMID- 20584538 TI - Quadruple valve replacement in patients with carcinoid heart disease. PMID- 20584539 TI - A set of rapid-response models for pollutant dispersion assessments in southern Spain coastal waters. AB - Three rapid-response Lagrangian particle-tracking dispersion models have been developed for southern Spain coastal waters. The three domains cover the Gulf of Cadiz (Atlantic Ocean), the Alboran Sea (Mediterranean), and the Strait of Gibraltar with higher spatial resolution. The models are based on different hydrodynamic submodels, which are run in advance. Tides are calculated using a 2D barotropic model in the three cases. Models used to obtain the residual circulation depend on the physical oceanography of each region. Thus, two-layer models are applied to Gibraltar Strait and Alboran Sea and a 3D baroclinic model is used in the Gulf of Cadiz. Results from these models have been compared with observations to validate them and are then used by the particle-tracking models to calculate dispersion. Chemical, radioactive and oil spills may be simulated, incorporating specific processes for each kind of pollutant. Several application examples are provided. PMID- 20584540 TI - A biofiltration model for tertiary nitrification of municipal wastewaters. AB - The main objective of this work concerns the evaluation of the biological aerated filtration model found in GPS-X, which had never been evaluated with adequate data. This model is interesting since it integrates the physical and biological phenomena involved during filtration with a low complexity of use. The validation of the model parameters combines experimental and theoretical approaches. Experimental data were recorded at a semi-industrial pilot scale submerged biofilter operated at a tertiary nitrification stage, receiving the effluent of a medium loaded activated sludge process for municipal wastewater. Also, several protocols were regularly applied to characterize the biofilm and the nitrogen removal performances: dry density and thickness of biofilm, nitrification rates and corresponding quantity of autotrophic biomass accumulated inside the filtering media, quantity of extracted autotrophic bacteria in the backwash water, nitrification capacity along the biofilter, as well as nitrogen compounds in the effluent. For short-term dynamic conditions, a set of reliable parameter values has been used to predict nitrogen removal for different data sets. For long-term dynamic periods, the need to adapt some of the parameters from one set of data to another is demonstrated. It is shown that the hydraulic loading rate and the backwashing frequency are the main parameters responsible for these modifications. PMID- 20584541 TI - EMPoWarMENT: Edmonton pediatric warfarin self-management pilot study in children with primarily cardiac disease. AB - Increasing numbers of children require warfarin thromboprophylaxis. Home INR testing by the patient (PST) has revolutionized warfarin management. However, the family/patient must contact the health team for guidance for warfarin dosing. Patient self management(PSM) prepares a patient performing PST to take an active role in warfarin dosing. Adult studies demonstrate that PSM is safe and effective with improved adherence and treatment satisfaction quality of life (QOL). OBJECTIVE: To estimate the safety and efficacy in children performing PSM or PST, to evaluate warfarin dose decision making in PSM, and warfarin related QOL. METHODS: Warfarinized children performing PST for >3m were randomized to PST or PSM. The PSM group underwent warfarin management education and assumed independent warfarin management. INRs were collected for a year prior to and for 1 year of study to determine TTR and warfarin decision making. QOL was assessed through inventory completion and interviews. RESULTS: 28 children were randomized and followed for 12 months. TTR was (83.9% pre/ post), and 77.7% pre to 83.0% post for PST and PSM (p=0.312). Appropriate warfarin decision making was 90% with no major bleeding episodes and no thromboembolic events. PSM was preferred by families. CONCLUSIONS: PSM for children may be a safe and effective management strategy for warfarinized children. Clinical studies with larger sample size are required. PMID- 20584542 TI - A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. AB - OBJECTIVE: The progression-free and median survival of patients with advanced ovarian cancer has not appreciably improved over the last decade. Novel targeted therapies, particularly antiangiogenic agents, may potentially improve clinical outcomes in patients with ovarian cancer. This phase II, open-label study evaluated oral pazopanib monotherapy in patients with low-volume recurrent ovarian cancer. METHODS: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with complete CA-125 response to initial platinum-based chemotherapy and subsequent elevation of CA-125 to >= 42 U/mL (> 2 * ULN) were treated with pazopanib 800 mg once daily until PD or unacceptable toxicity. This Green-Dahlberg study required 2 CA-125 responses in stage I (20 patients) to proceed to stage II (15 patients). The primary endpoint was CA-125 response (>= 50% decrease from baseline, confirmed >= 21 days after initial evaluation). RESULTS: Eleven of 36 patients (31%) had a CA-125 response to pazopanib, with median time to response of 29 days and median response duration of 113 days. Overall response rate was 18% in patients with measurable disease at baseline. The most common adverse events leading to discontinuation of study drug were grade 3 ALT (8%) and AST (8%) elevation. Only 1 grade 4 toxicity (peripheral edema) was reported. CONCLUSIONS: Pazopanib monotherapy was relatively well tolerated, with toxicity similar to other small-molecule, oral angiogenesis inhibitors, and demonstrated promising single-agent activity in patients with recurrent ovarian cancer. Further studies evaluating the potential role of pazopanib in patients with ovarian cancer are ongoing. PMID- 20584543 TI - Maternal dietary pattern during pregnancy is not associated with recurrent wheeze in children. AB - BACKGROUND: The rise in asthma prevalence over the last few decades may be a result of changes in prenatal or early-life environment, including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern. OBJECTIVE: To determine whether overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children. METHODS: A total of 1376 mother-infant pairs from Project Viva, a longitudinal prebirth cohort, who had responses for food frequency questionnaires in the first and second trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined by using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets. RESULTS: None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or the multivariable model (multivariable model, odds ratio per 1-point increase in Mediterranean diet, 0.98 [95% CI, 0.89 1.08]; AHEI-P, 1.07 [0.87-1.30]; Prudent, 1.02 [0.83-1.26]; Western, 0.98 [0.81 1.19]). CONCLUSION: Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants of offspring wheeze-associated illness than is dietary pattern. PMID- 20584544 TI - Infants aged 12 months can mount adequate serotype-specific IgG responses to pneumococcal polysaccharide vaccine. PMID- 20584545 TI - Successful long-term immunologic reconstitution by allogeneic hematopoietic stem cell transplantation cures patients with autosomal dominant hyper-IgE syndrome. PMID- 20584546 TI - Phl p 5 resorption in human oral mucosa leads to dose-dependent and time dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties. AB - BACKGROUND: Sublingual immunotherapy (SLIT) is safe and effective as treatment of allergic rhinitis and mild asthma. Oral mucosal Langerhans cells (oLCs) play a central role. However, little is known about allergen binding by oLCs during mucosal allergen resorption and its impact on oLC functions. OBJECTIVE: Binding of Phl p 5 to oLCs was studied in a standardized ex vivo model to investigate mechanisms important for SLIT. METHODS: Human oral mucosal biopsies were incubated with the grass pollen allergen Phl p 5. Migration, binding of Phl p 5, phenotype and cytokine production, and T-cell priming of Phl p 5-binding oLCs were analyzed. RESULTS: Significant uptake required more than 5 minutes, and dose dependent binding of Phl p 5 to oLCs was saturated at 100 microg/mL Phl p 5. Furthermore, Phl p 5 significantly increased the migratory capacity of oLCs but attenuated their maturation and strongly promoted the release of TGF-beta1 and IL 10 by oLCs themselves as well as by cocultured T cells. CONCLUSION: Oral mucosal Langerhans cells bind Phlp5 in a dose-dependent and time-dependent manner, leading to an increased production of tolerogenic cytokines and an enhanced migratory capacity but decelerated maturation of oLCs. PMID- 20584547 TI - Brief report: do delinquency and community violence exposure explain internalizing problems in early adolescent gang members? AB - Adolescent gang members are at higher risk for internalizing problems as well as exposure to community violence and delinquency. This study examined whether gang membership in early adolescence is associated with internalizing problems (depression, anxiety, and suicidal behavior) and whether these associations are mediated by delinquency and witnessing community violence. In a sample of 589 ethnically diverse early adolescents, gang membership was related to suicidal behavior but not depression or anxiety. Both delinquency and witnessing community violence mediated this association. Professionals working with gang members should assess these youth for suicidal behavior and provide interventions as needed. PMID- 20584548 TI - Preserved extracellular matrix components and retained biological activity in decellularized porcine mesothelium. AB - Mesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium was characterized for strength, composition of the matrix and biological activity. The tensile strength of the material was 40.65 +/- 21.65 N/cm. Extracellular matrix proteins collagen IV, fibronectin, and laminin as well as glycosaminoglycans were present in the material. Cytokines inherent in the extracellular matrix were preserved. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) were retained and the levels of VEGF and TGF-beta in the decellularized mesothelium were higher than those found in decellularized small intestinal submucosa (SIS). The decellularized mesothelium also stimulated human fibroblasts to produce more VEGF than fibroblasts grown on tissue culture plastic. Decellularized mesothelium is a sheet material with a combination of strength and biological activity that may have many potential applications in surgical repair and regenerative medicine. PMID- 20584550 TI - Association of temperament with subjective sleep patterns. AB - BACKGROUND: Emotional and cognitive functioning have been involved in insomnia etiology, and sleep disturbances are closely related to psychiatric disorders and personality traits. This study investigates the association of temperament with subjective sleep parameters. METHODS: In this web-survey, 5129 subjects (25.3% males) completed the Combined Emotional and Affective Temperament Scale (CEATS), which assesses emotional (fear, anger, drive and control) and affective (e.g. cyclothymic, hyperthymic) temperaments. Subjects also answered questions regarding subjective sleep parameters, psychiatric diagnosis, psychotropic medication intake and cigarette smoking. RESULTS: As control scores decreased, the later were the bed and the wake up time. Total sleep time was weakly associated with emotional temperaments. The higher the score of anger and the lower the score of control, the higher was the sleep-onset latency. As the anger score increased and the drive, fear and control scores decreased, the higher the number of nightly awakenings. The higher the drive and the control and the lower the anger scores, the better the sleep quality. For affective temperaments, depressives, labiles (related to ADHD) and cyclothymics (related to bipolar II disorders) go to bed and wake up later and have a worse profile regarding other sleep parameters. Hyperthymics and euthymics showed favorable sleep profiles. LIMITATIONS: Sample included a significant number of subjects with psychiatric diseases and on psychotropic medication. CONCLUSION: Dysregulated emotional activation (expressed as higher anger, and lower control and drive), as well as depressive, labile and cyclothymic affective temperaments were related to more dysfunctional sleep patterns. PMID- 20584549 TI - The use of microfiber composites of elastin-like protein matrix reinforced with synthetic collagen in the design of vascular grafts. AB - Collagen and elastin networks contribute to highly specialized biomechanical responses in numerous tissues and species. Biomechanical properties such as modulus, elasticity, and strength ultimately affect tissue function and durability, as well as local cellular behavior. In the case of vascular bypass grafts, compliance at physiologic pressures is correlated with increased patency due to a reduction in anastomotic intimal hyperplasia. In this report, we combine extracellular matrix (ECM) protein analogues to yield multilamellar vascular grafts comprised of a recombinant elastin-like protein matrix reinforced with synthetic collagen microfibers. Structural analysis revealed that the fabrication scheme permits a range of fiber orientations and volume fractions, leading to tunable mechanical properties. Burst strengths of 239-2760 mm Hg, compliances of 2.8-8.4%/100 mm Hg, and suture retention strengths of 35-192 gf were observed. The design most closely approximating all target criteria displayed a burst strength of 1483 +/- 143 mm Hg, a compliance of 5.1 +/- 0.8%/100 mm Hg, and a suture retention strength of 173 +/- 4 gf. These results indicate that through incorporation of reinforcing collagen microfibers, recombinant elastomeric protein-based biomaterials can play a significant role in load bearing tissue substitutes. We believe that similar composites can be incorporated into tissue engineering schemes that seek to integrate cells within the structure, prior to or after implantation in vivo. PMID- 20584551 TI - Oxytocin role in enhancing well-being: a literature review. AB - OBJECTIVES: Oxytocin (OT) has long been implicated in maternal bonding, sexual behavior and social affiliation behaviors. This paper reviews the wide effects of oxytocin and its key role in well-being. METHODS: Studies were identified through Medline, Pubmed, and PsychINFO search of the English-language literature from the past sixty years (1959 to 2009) using the key word "oxytocin" in human studies. Of the 287 articles identified, 102 were selected for review. RESULTS: OT induces a general sense of well-being including calm, improved social interactions, increased trust, and reduced fear as well as endocrine and physiological changes. Some central effects of OT are temporary and its release is associated with induction of secondary biochemical actions which mediate long-term benefits including blood pressure reduction, calm and affiliative behavior. As OT release is augmented by touch and physiological support so the hormone is involved in both the cause and benefits of social interactions. Just as OT has widespread effects in factors encompassing well-being, its dysfunction is associated with morbidity and decreased quality of life as observed neuropsychiatric conditions such as autism, schizophrenia and social phobias. CONCLUSIONS: Oxytocin (OT) is of potential use in enhancing interpersonal and individual well-being, and might have more applications in neuropsychiatric disorders especially those characterized by persistent fear, repetitive behavior, reduced trust and avoidance of social interactions. PMID- 20584552 TI - The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder. AB - INTRODUCTION: Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. METHODS: 64 patients with MDD were genotyped according to the above mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. RESULTS: Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. LIMITATIONS: The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. CONCLUSIONS: Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. PMID- 20584553 TI - Do patients with schizophrenia have a general or specific deficit in the perception of social threat? A meta-analytic study. AB - This study investigates whether social cognitive deficits found in patients with schizophrenia are specific to social threat stimuli, and whether the deficits increase across the delusion spectrum from a subclinical sample to clinical manifestation. The authors presented the meta-analytic review of the published literature on social threat perception performance in three kinds of group comparisons: a subclinical group and a healthy control group, a schizophrenia group and a healthy control group, and a schizophrenia with delusion symptoms group and a healthy control group. The meta-analysis of 20 studies yielded six weighted effect sizes. The largest differences were found between the schizophrenia with delusion group and the healthy controls in both the threat and non-threat conditions. No differences were found between the effect sizes in the threat-related condition and the non-threat condition in any of the three group comparisons. Age was found to be significantly correlated with the effect sizes. The performance differences in both the threat and non-threat conditions reflect a generalized performance deficit, rather than a specific deficit, in the perception of social threat stimuli among patients with schizophrenia. PMID- 20584554 TI - Association of anti-triosephosphate isomerase antibody and MRL/MpJ-Faslpr mouse. AB - The association between anti-triosephosphate isomerase (TPI) antibodies and MRL/MpJ-Fas(lpr) (MRL/lpr) mice was examined. We found that serum anti-TPI antibody levels in MRL/lpr mice, measured by enzyme-linked immunosorbent assay, were significantly higher than that of age-matched Balb/c mice and NZB/WF1 mice. Anti-TPI antibodies were detected in serum and cerebrospinal fluid in MRL/lpr mice by Western blotting. Inoculation of anti-TPI monoclonal antibody-producing hybridoma into the brain of Balb/c mice resulted in immunoglobulin deposition in the regions near the ventricles, hippocampus, and choroid plexus. Anti-TPI antibodies may play a role in the etiology of brain damage and behavioral deficits in MRL/lpr mice. PMID- 20584555 TI - Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume delineation of regional lymph node in patients with gastric carcinoma. AB - PURPOSE: To study the pattern of lymph node metastases (LNM) of gastric carcinoma (GC) and clarify the clinical target volume delineation of regional lymph node (CTVn). METHODS AND MATERIALS: The pattern of LNM of a total of 875 GC patients who had undergone gastrectomy and lymphadenectomy with more than 15 lymph nodes retrieved were retrospectively examined. The clinicopathologic factors related to LNM were analyzed using logistic regression analysis and linear regression. RESULTS: The rate of LNM in patients with upper GC was 75.3%, in middle ones 78.9%, in lower ones 64.9%, and 82.2% in patients with whole GCs. In terms of the ratio between metastatic and examined lymph nodes (N ratio) of GC patients, it was 35.8% in patients with upper tumors, 36.6% in middle ones, 27.6% in lower ones, and 51.0% in whole GCs. The maximum diameter and T stage of tumor emerged as statistically significant risk factors of the rate of LNM of GC (P<0.001, 0.001, respectively; HR=1.172, 2.132, respectively; 95% confidence interval: 1.083-1.268, 1.777-2.558, respectively). T stage (P<0.001), the maximum diameter of tumor (P<0.001), tumor differentiation (P=0.018) and macroscopic types of tumor (P=0.030) were significantly associated with N ratio. Our material showed an orderly spread to stations 1-16 clearly related to the position of the tumor (P<0. 001), nevertheless, there was no statistical difference between different locations of tumor with regards of the rate of LNM (P=0.614, HR=0.945, 95% confidence interval: 0.759-1.177) as well as N ratio (P>0.05). CONCLUSIONS: The pattern of LNM in GC is mainly correlated with the maximum diameter of tumor, T stage, macroscopic types and histologic differentiation. Rate of LNM and N ratio can be recommended as applicable parameters for lymph nodes involvement of GC. These factors should be considered comprehensively to design the CTVn for radiotherapy (RT) of GC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well. PMID- 20584556 TI - Gimeracil sensitizes cells to radiation via inhibition of homologous recombination. AB - BACKGROUND AND PURPOSE: 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. METHODS AND MATERIALS: We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. gamma-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. RESULTS: Results of gamma H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. CONCLUSIONS: Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways. PMID- 20584557 TI - Quantitative detection of Vibrio vulnificus in raw oysters by real-time loop mediated isothermal amplification. AB - Vibrio vulnificus is a significant cause of seafood-related morbidity and mortality in the United States. Rapid and sensitive detection assays are needed to facilitate better control of potential V. vulnificus infections from seafood consumption. Recently, loop-mediated isothermal amplification (LAMP) has been applied to detect V. vulnificus. In this study, the LAMP assay was coupled with either fluorescence- or turbidity-based real-time platforms for the quantitative detection of V. vulnificus in raw oysters. Both real-time platform assays possessed good specificity, with no false positive or false negative results among 38 V. vulnificus and 42 other bacteria tested. Comparable sensitivity was obtained using the two real-time platforms, with the assay limits of detection to be approximately 1-10 CFU/reaction of V. vulnificus in pure culture, up to 100 fold more sensitive than PCR. When applied to spiked oyster samples, the real time LAMP assays were able to detect 6.4x10(4) CFU/g of oyster without enrichment, 1000 fold more sensitive than PCR. Standard curves generated for detecting V. vulnificus in both pure culture and spiked oyster samples showed good linear regression between cell counts and the fluorescence Ct or turbidity Tt values. In summary, the real-time LAMP assays developed in the present study could be adopted for the quantitative detection of V. vulnificus in raw oysters with high sensitivity and specificity. PMID- 20584558 TI - Effect of hair color and sun sensitivity on nevus counts in white children in Colorado. AB - BACKGROUND: It has been widely reported that individuals with a light phenotype (ie, light hair color, light base skin color, and propensity to burn) have more nevi and are at greater risk for developing skin cancer. No studies have systematically investigated how phenotypic traits may interact in relation to nevus development. OBJECTIVE: We sought to systematically examine whether any combinations of phenotype are associated with a greater or lesser risk for nevus development in white children. METHODS: In the summer of 2007, 654 children were examined to determine full body nevus counts, skin color by colorimetry, and hair and eye color by comparison with charts. Interviews of parents were conducted to capture sun sensitivity, sun exposure, and sun protection practices. RESULTS: Among 9-year-old children with sun sensitivity rating type II (painful burn/light tan), those with light hair had lower nevus counts than did those with dark hair (P value for interaction = .03). This relationship was independent of eye color, presence of freckling, sex, usual daily sun exposure, sunburn in 2004 to 2007, sun protection index, and waterside vacation sun exposure. The difference in nevus counts was further determined to be specific to small nevi (<2 mm) and nevi in intermittently exposed body sites. LIMITATIONS: Geographic and genetic differences in other study populations may produce different results. CONCLUSION: The standard acceptance that dark phenotype is a marker for low melanoma risk and light phenotype a marker for high risk may need to be reevaluated. In non Hispanic white children, dark-haired individuals who burn readily and then tan slightly are more prone to nevus development, and may therefore be a previously underrecognized high-risk group for melanoma. PMID- 20584559 TI - Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma. AB - BACKGROUND: Merkel cell polyomavirus (MCV) was discovered by digital transcriptome subtraction as a monoclonal infection of Merkel cell carcinoma (MCC) tumors. Subsequent studies have repeatedly confirmed that MCV is the likely cause for most MCC. Polymerase chain reaction-based detection of the virus in other nonmelanoma skin cancers, however, has been inconsistent and controversial. OBJECTIVE: We sought to directly assay for MCV infection in squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) tumor cells by immunostaining for viral antigen. METHODS: CM2B4, a monoclonal antibody to exon 2 peptides of MCV T antigen, was used to examine tumors from 20 patients with MCC with and without secondary SCC or BCC tumors. RESULTS: MCV T antigen was readily detected in 15 (75%) of 20 MCC tumors including 11 MCC tumors from patients with secondary SCC or BCC. In contrast to MCC, none of these secondary BCC or SCC was MCV T-antigen positive. LIMITATIONS: A limitation was the small study size with antigen detection including only the MCV large T and 57kT proteins. CONCLUSIONS: MCV T antigen is generally not expressed in BCC or SCC tumors from a population favored to have MCV infection, ie, those persons already given the diagnosis of MCV positive MCC. This suggests that episodic polymerase chain reaction detection of MCV genome in BCC or SCC tumors may represent coincidental rather than causal infection, and that these tumors share other noninfectious risk factors. PMID- 20584560 TI - Digital squamous cell carcinoma and association with diverse high-risk human papillomavirus types. AB - Digital squamous cell carcinoma (SCC) presents a diagnostic challenge because of its relatively rare occurrence and mimicry of benign conditions. Although low risk human papillomavirus (HPV) subtypes are commonly associated with benign digital verrucae, digital SCC can be associated with high-risk, oncogenic HPV subtypes. We report 7 patients, including 4 HIV-positive patients, who presented with 10 lesions of digital SCC in situ. Six of 10 lesions were typed for HPV by immunostain or polymerase chain reaction. Multiple high-risk oncogenic subtypes were found, including HPV-16, -33, -51, and -73. The majority of reports linking HPV and digital SCCs have implicated the HPV-16 subtype. This case series highlights the diversity of oncogenic HPV types that may be associated with digital SCCs. Because the high rate of recurrence of digital SCCs may be a result of persistence of oncogenic HPV at the margins of resection, aggressive treatment of individual lesions and of genital reservoirs for HPV on patients and their sexual partners is warranted. PMID- 20584562 TI - Prediction of intrinsic solubility of generic drugs using MLR, ANN and SVM analyses. AB - The machine learning methods artificial neural network (ANN) and support vector machine (SVM) techniques were used to model intrinsic solubility of 74 generic drugs. The models obtained were compared with those obtained using multiple linear regression (MLR) analysis. Cluster analysis was used to split the data into a training set and test set. The appropriate descriptors were selected using a wrapper approach with multiple linear regressions as target learning algorithm. The descriptor selection and model building were performed with 10 fold cross validation using the training data set. The linear model fits the training set (n = 60) with R(2) = 0.814, while ANN and SVM higher values of R(2) = 0.823 and 0.835, respectively. Though the SVM model shows improvement of training set fitting, the ANN model was slightly superior to SVM and MLR in predicting the test set. The quantitative structure-property relationship study suggests that the theoretically calculated descriptors log P, first-order valence connectivity index ((1)chi(v)), delta chi (Delta(2)chi) and information content ((2)IC) have relevant relationships with intrinsic solubility of generic drugs studied. PMID- 20584563 TI - A bioactive labdane diterpenoid from Curcuma amada and its semisynthetic analogues as antitubercular agents. AB - A labdane diterpene dialdehyde was first time isolated from the chloroform extract of rhizomes of Curcuma amada. This compound exhibited antitubercular activity (MIC=500 microg/mL) against Mycobacterium tuberculosis H(37)Rv strain in BACTEC-460 assay. Two of its semisynthetic analogues also exhibited antitubercular activity at 250-500 microg/mL. It is the first report on isolation and antimycobacterial activity of this dialdehyde from C. amada. PMID- 20584564 TI - Body fluid retention and body weight change in anorexia nervosa patients during refeeding. AB - BACKGROUND & AIMS: Body weight gain is an important goal in anorexia nervosa (AN) patients, but inflation in body fluids could artificially increase body weight during refeeding. METHODS: 42 malnourished adult AN patients were refed using a normal-sodium diet, then 176 other malnourished adult AN patients received a refeeding low-sodium diet (BMI of the 218 patients: 13.4 +/- 1.9 kg/m(2)). Sodium balance, body composition by a 2-electrode impedance method (BIA, for assessment of total and extracellular water, fat-free mass, FFM), resting energy expenditure and energy intake were calculated. RESULTS: In the patients on normal-sodium diet, body weight, and total and extracellular water gains were higher than those of the low-sodium diet patients (P<0.01). Edema occurred more often in the former group (21% vs 6%; P<0.05). In almost all patients, BMI reached a plateau around 15-16 kg/m(2), then increased again. During this plateau, an increase in intracellular water and in "active FFM" was observed with BIA, together with a similar decrease in extracellular water. CONCLUSION: In AN patients, who are always afraid of gaining too much weight, in regard to their food intake, it will be useful to give a low-sodium diet until a 15-16 kg/m(2) BMI. This should be integrated into the cognitive behavioral therapy. PMID- 20584561 TI - Tyrosine kinases in inflammatory dermatologic disease. AB - Tyrosine kinases (TKs) are enzymes that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive an array of cellular responses including proliferation, differentiation, migration, and survival. Specific TKs have recently been identified as critical to the pathogenesis of several autoimmune and inflammatory diseases. Small-molecule inhibitors of TKs are emerging as a novel class of therapy that may provide benefit in certain patient subsets. In this review, we highlight TK signaling implicated in inflammatory dermatologic diseases, evaluate strategies aimed at inhibiting these aberrant signaling pathways, and discuss prospects for future drug development. PMID- 20584565 TI - Acetogenic fibers reduce fasting glucose turnover but not peripheral insulin resistance in metabolic syndrome patients. AB - BACKGROUND & AIMS: The acute ingestion of an acetogenic indigestible carbohydrate (lactulose) increased acetate turnover associated with decreased lipolysis (glycerol turnover) in insulin-resistant patients. It is not known whether a decreased lipolysis by chronic ingestion of acetogenic indigestible carbohydrates or fibers improves glucose turnover and insulin sensitivity. METHODS: Twenty-one men with metabolic syndrome ingested daily standardized drinks, with or without 28 g acetogenic fibers (acacia gum and pectin), for 5 weeks in a randomized double-blind crossover controlled study design. Euglycaemic-hyperinsulinaemic (EH) clamps coupled with kinetic studies were performed in the fasting state after treatments. RESULTS: Flatulence was more frequent with fiber treatment. Body weight, lipids as well as acetate and glycerol turnovers were unchanged. Fasting endogenous glucose turnover was improved after fiber treatment (7.9 +/- 1.3 MUmol kg(-1) min(-1)) compared with control (8.6 +/- 1.6 MUmol kg(-1) min( 1), P < 0.05). But insulin sensitivity (glucose infusion rate) during the EH clamp was not different at the end of fiber and control treatments, 3.7 +/- 1.8 and 3.8 +/- 1.5 mg kg(-1) min(-1), respectively, nor fasting plasma glucose and insulin. CONCLUSIONS: The chronic ingestion of acacia gum and pectin fibers did not decrease lipolysis but improved fasting endogenous glucose turnover with no effect on peripheral insulin resistance in metabolic syndrome patients. PMID- 20584566 TI - Perfluorinated compounds in the Antarctic region: ocean circulation provides prolonged protection from distant sources. AB - In order to investigate the extent to which Perfluorinated Contaminants (PFCs) have permeated the Southern Ocean food web to date, a range of Antarctic, sub Antarctic and Antarctic-migratory biota were analysed for key ionic PFCs. Based upon the geographical distribution pattern and ecology of biota with detectable vs. non-detectable PFC burdens, an evaluation of the potential contributory roles of alternative system input pathways is made. Our analytical findings, together with previous reports, reveal only the occasional occurrence of PFCs in migratory biota and vertebrate predators with foraging ranges extending into or north of the Antarctic Circumpolar Current (ACC). Geographical contamination patterns observed correspond most strongly with those expected from delivery via hydrospheric transport as governed by the unique oceanographic features of the Southern Ocean. We suggest that hydrospheric transport will form a slow, but primary, input pathway of PFCs to the Antarctic region. PMID- 20584567 TI - Minimally invasive surgically assisted rapid palatal expansion with limited approach under sedation: a report of 283 consecutive cases. AB - PURPOSE: An adequate transverse maxillary dimension is one of the critical aspects of a functional and stable occlusion. Surgically assisted rapid palatal expansion consists of a surgical liberation of the sites of resistance combined using orthopedic forces. Most technical descriptions advocate the use of general anesthesia with hospital admission. MATERIALS AND METHODS: Between March 2000 and July 2008, surgery was performed on 283 consecutive cases with transverse skeletal maxillary hypoplasia. The incision ran horizontally to reach the level of the laterals. Osteotomies of lateral walls and pterygoid disjunction were performed in all cases. A V-Y closure was performed in 2 layers. Patients were discharged after recovery from sedation. RESULTS: One hundred seventy-two of the 283 patients were male. Mean age was 18.3 years. Mean surgical time from incision to last suture was 19 minutes. Expanders were Hyrax in 221 cases and Haas in 61, and a bone-borne expander was used in 1 case. At the 1-year follow-up visit, mean expansion was 8.0 at the canines and 8.9 at the mesiovestibular cuspid of the first molar. General anesthesia has been classically advocated for these procedures, the argument being that pterygomaxillary disjunction was too traumatic to be performed under sedation. The surgical technique used sought to attain a balance between maximum mobilization of the maxilla with a complete liberation of all the buttresses and minimum morbidity to avoid further complications. CONCLUSIONS: The new technique that we report seeks to combine both aspects and allows for rapid intervention with local anesthesia plus sedation and a minimal approach with a total liberation of the maxillary resistances (piriform aperture pillars, zygomatic buttresses, midpalatal suture, and pterygoid junctions). The minimal approach and incision used in the technique guarantee vascular support to the maxilla via the vestibular corridors. PMID- 20584568 TI - Targeting microglial purinergic signaling to improve morphine analgesia. PMID- 20584569 TI - A motivational model of alcohol misuse in emerging adulthood. AB - Many emerging adults who have dropped out of high school are known to misuse alcohol. Expectancies and motives for drinking are pivotal in shaping the drinking behavior of emerging adults, especially those related to social influences. We tested a motivational model of problematic alcohol use using drinking motives (enhancement, social, conformity, coping) as multiple mediators to explain the association between social alcohol expectancies and alcohol misuse. A community sample of 104 individuals between ages 16 and 21 attending a General Educational Development (GED) program completed self-report measures of alcohol expectancies, drinking motives, quantity and frequency of drinking, and a structured interview that assessed the symptoms of alcohol use disorders. Results of multiple regression analysis testing multiple mediators indicated that social alcohol expectancies were associated with alcohol misuse through the mediated pathways of enhancement drinking motives. PMID- 20584570 TI - The frontal assessment battery (FAB) reveals neurocognitive dysfunction in substance-dependent individuals in distinct executive domains: Abstract reasoning, motor programming, and cognitive flexibility. AB - Substance-dependence is highly associated with executive cognitive function (ECF) impairments. However, considering that it is difficult to assess ECF clinically, the aim of the present study was to examine the feasibility of a brief neuropsychological tool (the Frontal Assessment Battery - FAB) to detect specific ECF impairments in a sample of substance-dependent individuals (SDI). Sixty-two subjects participated in this study. Thirty DSM-IV-diagnosed SDI, after 2weeks of abstinence, and 32 healthy individuals (control group) were evaluated with FAB and other ECF-related tasks: digits forward (DF), digits backward (DB), Stroop Color Word Test (SCWT), and Wisconsin Card Sorting Test (WCST). SDI did not differ from the control group on sociodemographic variables or IQ. However, SDI performed below the controls in DF, DB, and FAB. The SDI were cognitively impaired in 3 of the 6 cognitive domains assessed by the FAB: abstract reasoning, motor programming, and cognitive flexibility. The FAB correlated with DF, SCWT, and WCST. In addition, some neuropsychological measures were correlated with the amount of alcohol, cannabis, and cocaine use. In conclusion, SDI performed more poorly than the comparison group on the FAB and the FAB's results were associated with other ECF-related tasks. The results suggested a negative impact of alcohol, cannabis, and cocaine use on the ECF. The FAB may be useful in assisting professionals as an instrument to screen for ECF-related deficits in SDI. PMID- 20584571 TI - Failure to report attempts to quit smoking. AB - INTRODUCTION: Accurately assessing quit attempt history is important to develop population estimates of cessation and to increase our understanding of smoking trajectories. Thus, the current study investigated failure to report quit attempts as a function of length of quit attempt by time since quit attempt over the past year. METHODS: The present study used data from the Smoking Toolkit Study, a series of population-based surveys of smokers and recent ex-smokers in England aged 16 years and older. Among the 11,772 smokers identified at baseline (24.4% of the total sample), this study focused on the 4234 participants (36.0% of current smokers) who reported between one and three quit attempts in the past year. RESULTS: There was a strong trend for quit attempts that lasted for shorter periods of time to fail to be reported. After three months, 90.1% of those lasting less than one day, 63.7% of those lasting between a day a one week, and 38.9% of those lasting between one week and one month failed to be reported. CONCLUSION: A large proportion of unsuccessful quit attempts fail to be reported, particularly if they only last a short time or occurred longer ago. Therefore, population estimates of quit attempts based on retrospective data may be considerable underestimates and estimates of the success of quit attempts may be overestimates. Future research is needed to establish whether there is differential reporting of quit attempts as a function of features of attempts such as use of cessation aids. PMID- 20584572 TI - The mediation role of licit drugs in the influence of socializing on cannabis use among adolescents: A quantitative approach. AB - Licit substance use could be an early stage leading on to cannabis use. The aim of the study was to test a hypothetical sequential process leading from socializing to cannabis use so as to evaluate the mediator role of tobacco and alcohol. Data was derived from a French nationwide survey carried out in 2005 involving 29,393 teenagers aged 17. The analysis used structural equation modelling. The sequence tested was: socializing with friends-tobacco/alcohol use cannabis use-cannabis use disorders (CUD). Tobacco and alcohol consumptions appeared to be similarly influenced by the time spent with friends. However, tobacco mediation explained 57% of the sequence leading to cannabis use and 61% of the sequence leading to CUD, while the role of alcohol was weaker, at around 13%. Our results underline the effect of peer influence, in the course of night out socializing, on substance use among adolescents, and the importance of tobacco mediation in the process leading to cannabis use and misuse. This suggests that prevention in places frequented by adolescents should primarily target tobacco consumption, which explains the largest part of cannabis use variance. However, processes linking substance uses seem to be more complex, with the existence of reverse pathways from cannabis to licit drugs. Thus, the gateway effects of tobacco and alcohol require further exploration in relation to simultaneous polysubstance use. PMID- 20584573 TI - Binge drinking among gay, and lesbian youths: The role of internalized sexual stigma, self-disclosure, and individuals' sense of connectedness to the gay community. AB - We examined the prevalence of binge drinking among lesbian and gay (LG) youths, and evaluated whether experiences such as internalized sexual stigma, the experience of "coming out" to family and friends, and the individuals' sense of "connectedness" to the gay community could be associated with alcohol abuse. The research involved 119 gay (58.9%) and 83 lesbian (41.1%) Italian youths (18 to 24 years old). According to previous research, youths were categorized in non drinkers, social, binge and heavy drinkers. Results showed that the estimated percentage of binge drinking among gay and lesbian youths is 43.6%. The survey revealed that social, binge, and heavy drinkers differ in terms of some drinking variables, internalized sexual stigma, family and peer self-disclosure, and connectedness gay community. Implications for the prevention of binge drinking in LG youths are currently under discussion even if further investigation is urgently needed. PMID- 20584574 TI - Quality characteristics and composition of the longissimus muscle in the short loin from male and female farmed red deer in New Zealand. AB - Meat quality and composition characteristics are reported for the longissimus muscle from 10 red deer stags and 10 hinds aged about 20 months. All animals were pasture-finished but the stags and hinds came from different farms. The average carcass weight was 3.4 kg greater for the stag group (55.8 vs 52.4 kg; P=0.04), but measures of GR as a measure of fatness were similar and intramuscular fat content was significantly greater for the hind group (1.12% vs 0.63%; P<0.0001), as expected. The tenderness of cooked venison in terms of shear force and compression measures was significantly better for venison from the hind group, possibly due to the greater amount of intramuscular fat and slightly longer sarcomeres. The gender groups did not differ in absolute measures of colour or in the rate at which it deteriorated on display. However, the rate of colour deterioration was more rapid than other meats such as beef, as has been demonstrated elsewhere. The average ultimate pH and water-holding capacity were similar for the two groups. Venison from hinds contained more coenzyme Q(10), taurine, anserine, carnosine, and vitamin E. Group differences in fatty acid composition of intramuscular fat appeared to be mainly due to levels of fatness, which was greater for the hind group. PMID- 20584575 TI - Assessment of meat quality properties and development of a palatability prediction model for Korean Hanwoo steer beef. AB - Effects of the Korean carcass-grading system on carcass traits and meat quality parameters for the longissimus dorsi (LD) and semimembranosus (SM) muscles were investigated for Hanwoo steer beef. High quality grade beef cuts had significantly higher intramuscular fat content than those of low quality grade beef cuts. To establish a guaranteed system of eating quality for Hanwoo steer beef, a palatability prediction model was developed. The model development approach used canonical discriminant analysis and multivariate regression to assess effects of muscle type, cooking method, and aging treatment on Hanwoo beef quality grade. The palatability prediction model can provide Korean consumers with detailed information about expected eating quality for an individual cut, as well as provide critical information to the industry for maintaining high-quality beef production. The model is a significant advance in grading compared with the traditional carcass grading system, which applies a single quality grade to an entire carcass. PMID- 20584576 TI - Lack of benefit for the addition of androgen deprivation therapy to dose escalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer. AB - PURPOSE: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). METHODS AND MATERIALS: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA >=20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. RESULTS: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason >=8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. CONCLUSION: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study. PMID- 20584577 TI - Consolidation radiotherapy in primary central nervous system lymphomas: impact on outcome of different fields and doses in patients in complete remission after upfront chemotherapy. AB - PURPOSE: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. METHODS AND MATERIALS: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapse were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. RESULTS: At a median follow-up of 50 months, 21 patients are relapse free (5-year failure-free survival [FFS], 51%). WBRT doses >= 40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose >= 40 Gy. CONCLUSION: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity. PMID- 20584578 TI - Prostate intrafraction motion assessed by simultaneous kV fluoroscopy at MV delivery II: adaptive strategies. AB - PURPOSE: To investigate potential benefits of adaptive strategies for managing prostate intrafractional uncertainties when interfraction motion is corrected online. METHODS AND MATERIALS: Prostate intrafraction motion was measured using kV fluoroscopy during MV delivery for 571 fractions from 30 hypofractionated radiotherapy patients. We evaluated trending over treatment course using analysis of variance statistics, and we evaluated the ability to correct patient-specific systematic error and apply patient-specific statistical margins after 2 to 15 fractions to compensate 90% of motion. We also evaluated the ability to classify patients into small- and large-motion subgroups based on the first 2 to 20 fractions using discriminant analysis. RESULTS: No time trend was observed over treatment course, and intrafraction motion was patient specific (p < 0.0001). Systematic error in the first week correlated well with that in subsequent weeks, with correlation coefficients of 0.53, 0.50, and 0.41 in right-left (RL), anterior-posterior (AP), and superior-inferior (SI), respectively. After 5 fractions, the adaptive strategy resulted in average margin reductions of 0.3, 0.7, and 0.7 mm in RL, AP, and SI, respectively, with margins ranging from 1 to 3.2 mm in RL, 2 to 7.0 mm in AP, and 2 to 6.6 mm in SI. By contrast, population margins to include the same percentage of motion were 1.7, 4.0, and 4.1 mm. After 2 and 5 fractions, patients were classified into small- and large-motion groups with ~77% and ~83% accuracy. CONCLUSIONS: Adaptive strategies are feasible and beneficial for intrafraction motion management in prostate cancer online image guidance. Patients may be classified into large- and small-motion groups in early fractions using discriminant analysis. PMID- 20584579 TI - Application of a novel dose-uncertainty model for dose-uncertainty analysis in prostate intensity-modulated radiotherapy. AB - PURPOSE: To analyze dose uncertainty using a previously published dose uncertainty model, and to assess potential dosimetric risks existing in prostate intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: The dose uncertainty model provides a three-dimensional (3D) dose-uncertainty distribution in a given confidence level. For 8 retrospectively selected patients, dose uncertainty maps were constructed using the dose-uncertainty model at the 95% CL. In addition to uncertainties inherent to the radiation treatment planning system, four scenarios of spatial errors were considered: machine only (S1), S1 + intrafraction, S1 + interfraction, and S1 + both intrafraction and interfraction errors. To evaluate the potential risks of the IMRT plans, three dose-uncertainty based plan evaluation tools were introduced: confidence-weighted dose-volume histogram, confidence-weighted dose distribution, and dose-uncertainty-volume histogram. RESULTS: Dose uncertainty caused by interfraction setup error was more significant than that of intrafraction motion error. The maximum dose uncertainty (95% confidence) of the clinical target volume (CTV) was smaller than 5% of the prescribed dose in all but two cases (13.9% and 10.2%). The dose uncertainty for 95% of the CTV volume ranged from 1.3% to 2.9% of the prescribed dose. CONCLUSIONS: The dose uncertainty in prostate IMRT could be evaluated using the dose-uncertainty model. Prostate IMRT plans satisfying the same plan objectives could generate a significantly different dose uncertainty because a complex interplay of many uncertainty sources. The uncertainty-based plan evaluation contributes to generating reliable and error-resistant treatment plans. PMID- 20584580 TI - Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer. AB - PURPOSE: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. METHODS AND MATERIALS: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. RESULTS: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). CONCLUSION: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not. PMID- 20584582 TI - Radiological and clinical pneumonitis after stereotactic lung radiotherapy: a matched analysis of three-dimensional conformal and volumetric-modulated arc therapy techniques. AB - PURPOSE: Lung fibrosis is common after stereotactic body radiotherapy (SBRT) for lung tumors, but the influence of treatment technique on rates of clinical and radiological pneumonitis is not well described. After implementing volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) for SBRT, we scored the early pulmonary changes seen with arc and conventional three dimensional SBRT (3D-CRT). METHODS AND MATERIALS: Twenty-five SBRT patients treated with RA were matched 1:2 with 50 SBRT patients treated with 3D-CRT. Dose fractionations were based on a risk-adapted strategy. Clinical pneumonitis was scored using Common Terminology Criteria for Adverse Events version 3.0. Acute radiological changes 3 months posttreatment were scored by three blinded observers. Relationships among treatment type, baseline factors, and outcomes were assessed using Spearman's correlation, Cochran-Mantel-Haenszel tests, and logistic regression. RESULTS: The RA and 3D-CRT groups were well matched. Forty three patients (57%) had radiological pneumonitis 3 months after treatment. Twenty-eight patients (37%) had computed tomography (CT) findings of patchy or diffuse consolidation, and 15 patients (20%) had ground-glass opacities only. Clinical pneumonitis was uncommon, and no differences were seen between 3D-CRT vs. RA patients in rates of grade 2/3 clinical pneumonitis (6% vs. 4%, respectively; p = 0.99), moderate/severe radiological changes (24% vs. 36%, respectively, p = 0.28), or patterns of CT changes (p = 0.47). Radiological severity scores were associated with larger planning target volumes (p = 0.09) and extended fractionation (p = 0.03). CONCLUSIONS: Radiological changes after lung SBRT are common with both approaches, but no differences in early clinical or radiological findings were observed after RA. Longer follow-up will be required to exclude late changes. PMID- 20584583 TI - Impact of sequencing of postmastectomy radiotherapy and breast reconstruction on timing and rate of complications and patient satisfaction. AB - PURPOSE: There are few long-term studies of how the sequencing of postmastectomy radiotherapy (PMRT) and breast reconstruction (BR) affects the time to development of complications or patient satisfaction with BR. We therefore studied this issue. METHODS AND MATERIALS: One hundred thirteen women who underwent BR at Beth Israel Deaconess Medical Center (Boston, MA) from 1999-2006 and also received PMRT were included. Complications requiring surgery were categorized as early (within 90 days of BR) or late. The median length of follow up after BR was 46.5 months. Patients' general and esthetic satisfaction was assessed with a validated questionnaire. RESULTS: Complications occurred among 32% of 57 women receiving PMRT before BR and 44% of 57 patients having BR before PMRT (p = 0.176). Early complications were more frequent in patients who had PMRT first (18%) than for those with BR first (11%) (p = 0.210); conversely, late complication rates in the two groups were 14% and 33%, respectively (p = 0.009). General satisfaction was comparable between the PMRT-first and BR-first groups (68% and 68%, respectively; p = 0.995); esthetic satisfaction rates were also similar (50% and 62%, respectively; p = 0.238). CONCLUSIONS: The sequencing of PMRT and BR did not have a substantial impact on the total risk of complications or patients' general and esthetic satisfaction. However, early complications tended to develop in patients having PMRT first, whereas patients having BR first had a higher risk of late complications. Additional study of the effects of sequencing of PMRT on particular types of reconstructions may help devise strategies for reducing these risks. PMID- 20584581 TI - Proteomic analysis of radiation-induced changes in rat lung: Modulation by the superoxide dismutase mimetic MnTE-2-PyP(5+). AB - PURPOSE: To identify temporal changes in protein expression in the irradiated rat lung and generate putative mechanisms underlying the radioprotective effect of the manganese superoxide dismutase mimetic MnTE-2-PyP(5+). METHODS AND MATERIALS: Female Fischer 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy and killed from day 1 to 20 weeks after irradiation. Proteomic profiling was performed to identify proteins that underwent significant changes in abundance. Some irradiated rats were administered MnTE-2-PyP(5+) and changes in protein expression and phosphorylation determined at 6 weeks after irradiation. RESULTS: Radiation induced a biphasic stress response in the lung, as shown by the induction of heme oxygenase 1 at 1-3 days and at 6-8 weeks after irradiation. At 6-8 weeks after irradiation, the down-regulation of proteins involved in cytoskeletal architecture (filamin A and talin), antioxidant defense (biliverdin reductase and peroxiredoxin II), and cell signaling (beta-catenin, annexin II, and Rho-guanosine diphosphate dissociation inhibitor) was observed. Treatment with MnTE-2-PyP(5+) partially prevented the apparent degradation of filamin and talin, reduced the level of cleaved caspases 3 and 9, and promoted Akt phosphorylation as well as beta-catenin expression. CONCLUSION: A significant down-regulation of proteins and an increase in protein markers of apoptosis were observed at the onset of lung injury in the irradiated rat lung. Treatment with MnTE-2-PyP(5+), which has been demonstrated to reduce lung injury from radiation, reduced apparent protein degradation and apoptosis indicators, suggesting that preservation of lung structural integrity and prevention of cell loss may underlie the radioprotective effect of this compound. PMID- 20584584 TI - Impact of cranial irradiation added to intrathecal conditioning in hematopoietic cell transplantation in adult acute myeloid leukemia with central nervous system involvement. AB - PURPOSE: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). METHODS AND MATERIALS: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). RESULTS: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0 3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. CONCLUSIONS: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies. PMID- 20584585 TI - Bevacizumab, capecitabine, amifostine, and preoperative hypofractionated accelerated radiotherapy (HypoArc) for rectal cancer: a Phase II study. AB - PURPOSE: Bevacizumab has established therapeutic activity in patients with metastatic colorectal cancer, and anti-vascular endothelial growth factor therapy enhances the activity of radiotherapy in experimental models. We assessed the feasibility and efficacy of preoperative radiochemotherapy combined with bevacizumab in patients with rectal cancer. METHODS AND MATERIALS: Nineteen patients with radiologic T3 and/or N+ rectal carcinoma were treated with preoperative conformal hypofractionated accelerated radiotherapy (3.4 Gy in 10 consecutive fractions) supported with amifostine (500-1,000 mg daily), capecitabine (600 mg/m(2) twice daily, 5 days per week), and bevacizumab (5 mg/kg every 2 weeks for 2 cycles). Surgery followed 6 weeks after the end of radiotherapy. A cohort of 14 sequential patients treated with the same regimen without bevacizumab was available for comparison. RESULTS: Grade 2 or 3 diarrhea was noted in 7 of 19 patients (36.8%), which was statistically worse than patients receiving the same regimen without bevacizumab (p = 0.01). A higher incidence of Grade 2 or 3 proctalgia was also noted (21.1%) (p = 0.03). Bladder and skin toxicity was negligible. All toxicities regressed completely within 2 weeks after the end of therapy. Pathologic complete and partial response was noted in 7 of 19 cases (36.8%) and 8 of 19 cases (42.1%). Within a median follow up of 21 months, none of the patients has had late complications develop and only 1 of 18 evaluable cases (5.5%) has had locoregional relapse. CONCLUSIONS: Bevacizumab can be safely combined with hypofractionated radiotherapy and capecitabine as a preoperative radiochemotherapy regimen for patients with rectal cancer. The high pathologic complete response rates urges the testing of bevacizumab in randomized studies. PMID- 20584586 TI - Continuous arc rotation of the couch therapy for the delivery of accelerated partial breast irradiation: a treatment planning analysis. AB - PURPOSE: We present a novel form of arc therapy: continuous arc rotation of the couch (C-ARC) and compare its dosimetry with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) for accelerated partial breast irradiation (APBI). C ARC, like VMAT, uses a modulated beam aperture and dose rate, but with the couch, not the gantry, rotating. METHODS AND MATERIALS: Twelve patients previously treated with APBI using 3D-CRT were replanned with (1) C-ARC, (2) IMRT, and (3) VMAT. C-ARC plans were designed with one medial and one lateral arc through which the couch rotated while the gantry was held stationary at a tangent angle. Target dose coverage was normalized to the 3D-CRT plan. Comparative endpoints were dose to normal breast tissue, lungs, and heart and monitor units prescribed. RESULTS: Compared with 3D-CRT, C-ARC, IMRT, and VMAT all significantly reduced the ipsilateral breast V50% by the same amount (mean, 7.8%). Only C-ARC and IMRT plans significantly reduced the contralateral breast maximum dose, the ipsilateral lung V5Gy, and the heart V5%. C-ARC used on average 40%, 30%, and 10% fewer monitor units compared with 3D-CRT, IMRT, and VMAT, respectively. CONCLUSIONS: C-ARC provides improved dosimetry and treatment efficiency, which should reduce the risks of toxicity and secondary malignancy. Its tangent geometry avoids irradiation of critical structures that is unavoidable using the en face geometry of VMAT. PMID- 20584587 TI - Effect of nodal irradiation and fraction size on cardiac and cerebrovascular mortality in women with breast cancer treated with local and locoregional radiotherapy. AB - PURPOSE: To determine whether the adjuvant breast cancer radiation volume or fraction size (>2 Gy vs. <=2 Gy) affected the risk of fatal cardiac or cerebrovascular (CCV) events and to determine whether the addition of regional radiotherapy (RT) increased the risk of fatal cerebrovascular events compared with breast/chest wall RT alone. METHODS AND MATERIALS: Overall survival was compared for patients receiving breast/chest wall RT alone or breast/chest wall plus regional node RT (BRCW+NRT) in a population-based cohort of women with early stage breast cancer who had undergone RT between 1990 and 1996. The effect of laterality, age, systemic therapy, radiation volume, and fraction size on the risk of fatal CCV events was analyzed using a competing risk method. RESULTS: A total of 4,929 women underwent adjuvant RT. The median follow-up was 11.7 years. BRCW+NRT was associated with an increased risk of CCV death at 12 years (5% for BRCW+NRT vs. 3.5% for breast/chest wall RT alone; p = .004), but the fraction size was not (3.92% for a fraction size >2 Gy vs. 3.54% for a fraction size <2 Gy; p = .83). The 12-year absolute risk of death from stroke alone did not differ for either radiation volume (1.17% for BRCW+NRT vs. 0.8% for breast/chest wall RT alone; p = .22) or fraction size (p = .59). CONCLUSION: Regional RT was associated with a small (1.5% at 12 years), but statistically significant, increased risk of death from a CCV event. The addition of regional RT did not significantly increase the risk of death from stroke, although the number of events was small. An increased fraction size was not significantly associated with a greater risk of fatal CCV events. These data support the continued use of hypofractionated adjuvant regional RT. PMID- 20584588 TI - Rates of fetal alcohol exposure among newborns in a high-risk obstetric unit. AB - Meconium fatty acid ethyl esters (FAEEs) are sensitive and specific biomarkers for prenatal alcohol exposure (PAE) in pregnancy. We recently reported a 2.5% rate of FAEE positive meconium in a general population sample of infants born in the region of Grey-Bruce, Ontario. Women in this region with high-risk pregnancies are transferred to a tertiary care facility in London, Ontario. The objective of this study was to determine, in a population-based sample, whether high-risk pregnancies are associated with an increased risk of in utero alcohol exposure. Grey-Bruce residents transferred to the high-risk obstetric unit of St. Joseph's Health Care in London, Ontario were identified and consented to this anonymous prevalence study. Meconium was collected and analyzed for FAEE using gas chromatography with mass spectrometry. The prevalence of FAEE positive meconium was compared with the population-based prevalence in the Grey-Bruce. Fifty meconium specimens were collected from August 1, 2006 to July 31, 2007. Fifteen (30%) specimens tested positive for FAEE. The results indicate that infants born in the high-risk obstetric unit had a 12-fold higher risk of screening positive for second and third trimester alcohol exposure compared with infants born in the general population of Grey-Bruce (relative risk=12.04, 95% confidence interval=6.40-22.65, P<.0001). These results suggest that the high risk pregnancies should be screened for PAE and followed-up for potential diagnosis of fetal alcohol spectrum disorder. PMID- 20584589 TI - Lymph node management in clinically node-negative patients with papillary thyroid carcinoma. AB - AIMS: Systematic lymph node dissection in patients with papillary thyroid carcinoma (PTC) remains controversial. The objective of this study was to study the pattern of lymph node spread in patients with PTC clinically node-negative and then to propose a lymph node management strategy. METHODS: We retrospectively reviewed the records of patients who had undergone total thyroidectomy and a systematic central neck dissection (CND) and lateral neck dissection. Ninety patients with PTC without lymph nodes metastases (LNM) detected on preoperative palpation and ultrasonographic examination were included. RESULTS: Forty-one patients (45.5%) had LNM. Twenty-eight patients (31%) had a central and a lateral involvement. Thirteen patients (14.5%) had only a central involvement. All the patients without LNM in the central compartment were also free in the lateral compartment. There was no correlation between LNM status and TNM staging. The largest LNM in the central compartment was smaller than or equal to 5mm in 66% of the cases, and that could explain the lack of sensitivity of the preoperative ultrasonographic examination. CONCLUSION: CND could be considered at preoperative or intraoperative diagnosis of PTC whereas lateral neck dissection should be performed only in patients with preoperative suspected and/or intraoperatively proven LNM. Systematic CND allows an objective evaluation of lymph node status in this central cervical area where the LNM are particularly small and difficult to detect preoperatively. PMID- 20584590 TI - Correlation or coincidence between monocytosis and worsening of psychotic symptoms in veterans with schizophrenia? PMID- 20584591 TI - The changing aetiology of head and neck cancer: the role of human papillomavirus. AB - Human papillomavirus (HPV) is associated with the development of a subset of head and neck cancers arising in the oropharynx, which includes the tonsils, base of tongue and soft palate. HPV-associated oropharyngeal cancer (OPC) seems to be rapidly increasing in incidence in many countries, including the USA, Sweden and Greece, and is known to affect younger patients who are less likely to have been exposed to the carcinogenic effects of tobacco and alcohol than their HPV negative counterparts. There is accumulating evidence from prospective studies that HPV-positive OPC responds better to treatment, including chemotherapy and radiotherapy, than HPV-negative OPC, and that patients with HPV-positive disease have excellent long-term survival rates. To date, patients with HPV-positive and HPV-negative OPC are managed according to common treatment protocols; this may no longer be appropriate in an age when the delivery of targeted treatment, tailored to individual tumour and patient characteristics, is becoming a reality. This review summarises our current understanding of HPV-positive OPC, drawing parallels from the role of HPV in the development of cervical cancer. We also consider how knowledge of tumour HPV status may affect the future management and prevention of OPC and discuss the need for future collaborative trials in this important group of patients. PMID- 20584592 TI - Split-course hypofractionated palliative radiotherapy for patients with head and neck squamous cell carcinoma - a worthwhile treatment schedule in the UK? PMID- 20584593 TI - The efficacy of preventing neutropenic sepsis in patients with testicular germ cell tumours: results of two consecutive audits. PMID- 20584594 TI - Chemoradiotherapy for cervical cancer--do questions remain? PMID- 20584595 TI - Difference between patient-reported side effects of ciclesonide versus fluticasone propionate. AB - RATIONALE: Patient-reported outcomes provide new insights into the dynamics of asthma management. Further to asthma control and quality of life, self-reported side effects of treatment can be assessed with the validated Inhaled Corticosteroid Questionnaire (ICQ). OBJECTIVES: To compare patient-reported side effects between the inhaled corticosteroids ciclesonide and fluticasone propionate. METHODS: Patients with moderate or moderate-to-severe asthma, pre treated with a constant dose and type of medication, were randomized in three separate studies: 1) once daily ciclesonide 320 MUg (n = 234) or twice daily fluticasone propionate 200 MUg (n = 240); 2) twice daily ciclesonide 320 MUg (n = 255) or twice daily fluticasone propionate 375 MUg (n = 273); and 3) twice daily ciclesonide 320 MUg (n = 259) or twice daily fluticasone propionate 500 MUg (n = 244). Patients rated the side effect questions of the 15 domain ICQ on a 7-point Likert scale (0 = not at all, 6 = a very great deal) during scheduled visits. RESULTS: The majority of side effect scores remained similar with ciclesonide but worsened statistically significantly with fluticasone propionate from baseline to the end of the study in within-treatment analyses. In between-treatment analyses of studies 1 and 3 ciclesonide significantly improved total side effect scores (p < 0.025) and 14 out of 30 individual local and systemic domain scores (p < 0.025) compared with fluticasone propionate. In Study 2, although ciclesonide improved the majority of scores compared with fluticasone propionate only 'oropharyngeal itching' reached statistical significance (p < 0.025, one-sided). CONCLUSION: Patient-perceived side effects differ depending on the type of inhaled corticosteroids used. Patients with moderate-to-severe asthma report less intense side effects assessed with ICQ with ciclesonide than with fluticasone propionate. CLINICAL TRIAL REGISTRATION: The reported trials were completed before July 1 2005 and, therefore, are not registered. PMID- 20584596 TI - An ecotoxicological approach for hazard identification of energy ash. AB - Within the EU, ash should be classified by its inherent hazardous effects under criterion H-14 (ecotoxic) in the Directive on waste (2008/98/EC). Today, however, there are no harmonized quantitative criterions for such a classification, but it is stated that biological test systems can be used. In this study seven ash materials were leached and characterized, both biologically and chemically. The objectives were to evaluate if (a) clear concentration-response relationships could be achieved for the selected toxicity tests (bacteria, algae, crustacean and fish), (b) some test(s) are generally more sensitive and (c) the toxic responses were consistent with the chemical analyzes. Interestingly, our results indicate that high concentrations of non-hazardous components (Ca, K) influenced the toxicity of almost all ash eluates, whereas hazardous components (e.g. Zn, Pb) only influenced the toxicity of the eluates ranked as most hazardous. If considering both hazardous and non-hazardous substances, the observed toxic responses were relatively consistent with the chemical analyzes. Our results further showed that the (sub)chronic tests were much more sensitive than the acute tests. However, the use of extrapolation factors to compensate for using the less sensitive acute tests will likely lead to either over- or underestimations of toxicity. Our recommendation is therefore that classification of waste according to H-14 should be based on (sub)chronic test data. Finally, given that treatment of the eluates prior to toxicity testing has a major significance on the concentration and speciation of released substances, further studies are needed in order to propose a relevant testing scheme. PMID- 20584597 TI - Measurements of particulate matter concentrations at a landfill site (Crete, Greece). AB - Large amounts of solid waste are disposed in landfills and the potential of particulate matter (PM) emissions into the atmosphere is significant. Particulate matter emissions in landfills are the result of resuspension from the disposed waste and other activities such as mechanical recycling and composting, waste unloading and sorting, the process of coating residues and waste transport by trucks. Measurements of ambient levels of inhalable particulate matter (PM(10)) were performed in a landfill site located at Chania (Crete, Greece). Elevated PM(10) concentrations were measured in the landfill site during several landfill operations. It was observed that the meteorological conditions (mainly wind velocity and temperature) influence considerably the PM(10) concentrations. Comparison between the PM(10) concentrations at the landfill and at a PM(10) background site indicates the influence of the landfill activities on local concentrations at the landfill. No correlation was observed between the measurements at the landfill and the background sites. Finally, specific preventing measures are proposed to control the PM concentrations in landfills. PMID- 20584598 TI - Enhanced chromate reduction by resting Escherichia coli cells in the presence of quinone redox mediators. AB - The reduction of Cr(VI) by resting Escherichia coli cells was significantly enhanced by the quinone redox mediators, lawsone, menadione, anthraquinone-2 sulfonate and anthraquinone-2,6-disulfonate. In the presence of 0.2 mM lawsone, over 97.5% Cr(VI) (100 mg l(-1)) was reduced in 4h. The mediated reduction occurred at initial Cr(VI) concentrations of 50-250 mg l(-1), and increased with increasing initial biomass concentrations from 0.05 to 1.2 g l(-1). The addition of glucose as electron donor promoted the reduction process. Cu(2+), Ni(2+) and Co(2+) inhibited, whereas Mn(2+) and Pb(2+) stimulated reduction. Four rounds of mediated reduction were completed in 19 h, suggesting its stability and persistence. The efficient mediated microbial reduction of Cr(VI) is promising for rapid anaerobic removal of chromate. PMID- 20584600 TI - Bioethanol production from Lantana camara (red sage): Pretreatment, saccharification and fermentation. AB - Lantanacamara contains 61.1% (w/w) holocellulose and can serve as a low-cost feedstock for bioethanol production. Acid hydrolysis (3.0%, v/v H(2)SO(4), 120 degrees C for 45 min) of L. camara produced 187.14 mg/g total sugars along with fermentation inhibitors such as phenolics (8.2mg/g), furfurals (5.1mg/g) and hydroxy methyl furfurals (6.7 mg/g). Sequential application of overliming (pH 10.0) and activated charcoal (1.5%, w/v) adsorption was used to remove these toxic compounds from the acid hydrolysate. The acid-pretreated biomass of L. camara was further delignified through combined pretreatment of sodium sulphite (5.0% w/v) and sodium chlorite (3.0% w/v), which resulted in about 87.2% lignin removal. The enzymatic hydrolysis of delignified cellulosic substrate showed 80.0% saccharification after 28 h incubation at 50 degrees C and pH 5.0. Fermentation of acid and enzymatic hydrolysates with Pichiastipitis and Saccharomycescerevisiae gave rise to 5.16 and 17.7 g/L of ethanol with corresponding yields of 0.32 and 0.48 g/g after 24 and 16 h, respectively. PMID- 20584599 TI - Isolation and identification of 5-hydroxyl-5-methyl-2-hexenoic acid from Actinoplanes sp. HBDN08 with antifungal activity. AB - A bioactivity-guided approach was employed to isolate and determine the chemical identity of bioactive constituents with antifungal activity from Actinoplanes sp. HBDN08. The structure of the antifungal metabolite was elucidated as 5-hydroxyl-5 methyl-2-hexenoic acid on the basis of spectral analysis. This compound showed strong in vitro antifungal activity against Botrytis cinerea, Cladosporium cucumerinum and Corynespora cassiicola, with an IC(50) of 32.45, 27.17, and 30.66 mg/L, respectively; however, it only moderately inhibited hyphal growth of Rhizoctonia solani with an IC(50) of 61.64 mg/L. The in vivo antifungal activity under greenhouse conditions demonstrated that 5-hydroxyl-5-methyl-2-hexenoic acid could effectively control the diseases caused by B. cinerea, C. cucumerinum and C. cassiicola with 71.42%, 78.63% and 65.13% control values at 350 mg/L, respectively. This strong antifungal activity suggests that 5-hydroxyl-5-methyl-2 hexenoic acid might be a promising candidate for new antifungal agents. PMID- 20584601 TI - Evaluation of autotrophic and heterotrophic processes in biofilm reactors used for removal of sulphide, nitrate and COD. AB - Microbial cultures originated from an oil reservoir were used in three biofilm reactors and effects of sulphide and nitrate loading rates and molar loading ratio on the removal of sulphide, nitrate and acetate, and composition of end products were investigated. Application of biofilms improved sulphide and nitrate removal rates significantly when compared with freely suspended cells. Maximum sulphide and nitrate removal rates under autotrophic conditions were 30.0 and 24.4 mM h(-1), respectively (residence time: 0.5h). Oxidation of acetate occurred only at nitrate to sulphide molar loading ratios around 0.7 or higher when nitrate was present at levels higher than that required for oxidation of sulphide to sulphur. Conversion of sulphide to sulphate increased from 0% to 66% as nitrate to sulphide molar loading ratio was increased from 0.34 to 3.98. The highest nitrate and acetate removal rates in the bioreactor operated under heterotrophic conditions were 183.2 and 88.0 mM h(-1), respectively (residence time: 0.8h). PMID- 20584602 TI - Growth characteristics of Botryococcus braunii 765 under high CO2 concentration in photobioreactor. AB - To understand the potential of cultivating Botryococcus braunii with flue gas (normally containing high CO(2)) for biofuel production, growth characteristics of B. braunii 765 with 2-20% CO(2) aeration were investigated. The results showed that the strain could grow well without any obvious inhibition under all tested CO(2) concentrations with an aeration rate of 0.2 vvm, even without any culture pH adjustment (ranged from 6.0 to 8.0). The maximum biomass among all conditions was 2.31 g L(-1) on 25th day at 20% CO(2). Hydrocarbon content and algal colony size increased with the increase of CO(2) concentration. A negative correlation between algal biomass and culture total phosphorus was observed (from -0.828 to 0.911, P<0.01). Additionally, 2% sodium hypochlorite solution was used for photobioreactor sterilization to cultivate B. braunii. PMID- 20584603 TI - Efficient salt removal in a continuously operated upflow microbial desalination cell with an air cathode. AB - Microbial desalination cells (MDCs) hold great promise for drinking water production because of potential energy savings during the desalination process. In this study, we developed a continuously operated MDC--upflow microbial desalination cell (UMDC) for the purpose of salt removal. During the 4-month operation, the UMDC constantly removed salts and generated bio-electricity. At a hydraulic retention time (HRT) of 4 days (salt solution) and current production of ~62 mA, the UMDC was able to remove more than 99% of NaCl from the salt solution that had an initial salt concentration of 30 g total dissolved solids (TDS)/L. In addition, the TDS removal rate was 7.50 g TDSL(-1)d(-1) (salt solution volume) or 5.25 g TDSL(-1)d(-1) (wastewater volume), and the desalinated water met the drinking water standard, in terms of TDS concentration. A high charge transfer efficiency of 98.6% or 81% was achieved at HRT 1 or 4d. The UMDC produced a maximum power density of 30.8 W/m(3). The phenomena of bipolar electrodialysis and proton transport in the UMDC were discussed. These results demonstrated the potential of the UMDC as either a sole desalination process or a pre-desalination reactor for downstream desalination processes. PMID- 20584604 TI - Cyclic amide bioisosterism: strategic application to the design and synthesis of HCV NS5B polymerase inhibitors. AB - Conformational modeling has been successfully applied to the design of cyclic bioisosteres used to replace a conformationally rigid amide bond in a series of thiophene carboxylate inhibitors of HCV NS5B polymerase. Select compounds were equipotent with the original amide series. Single-point mutant binding studies, in combination with inhibition structure-activity relationships, suggest this new series interacts at the Thumb-II domain of NS5B. Inhibitor binding at the Thumb II site was ultimately confirmed by solving a crystal structure of 8b complexed with NS5B. PMID- 20584605 TI - Ceratinadins A-C, new bromotyrosine alkaloids from an Okinawan marine sponge Pseudoceratina sp. AB - Three new bromotyrosine alkaloids, ceratinadins A-C (1-3), were isolated from an Okinawan marine sponge Pseudoceratina sp. and the structures of 1-3 were elucidated on the basis of spectroscopic data. Ceratinadin A (1) was a novel bromotyrosine alkaloid possessing an N-imidazolyl-quinolinone moiety. Ceratinadins A (1) and B (2) showed antifungal activity. PMID- 20584606 TI - Natural products-based insecticidal agents 6. Design, semisynthesis, and insecticidal activity of novel monomethyl phthalate derivatives of podophyllotoxin against Mythimna separata Walker in vivo. AB - To discover the more potent analogs, 12 novel monomethyl phthalate derivatives of podophyllotoxin were synthesized and preliminarily tested against the pre-third instar larvae of Mythimna separata Walker in vivo at the concentration of 1mg/mL. Compounds 8e-i showed the higher insecticidal activity than podophyllotoxin. Especially 8g exhibited the most potent insecticidal activity compared with toosendanin, a commercially available insecticide derived from Melia azedarach. The structure-activity relationships demonstrated that trans-lactone, 4beta substitution, 2beta-chlorine substitution, and 4'-methoxy group were the important structural properties of podophyllotoxins for good insecticidal activity. PMID- 20584607 TI - N-demethylation of N-methyl alkaloids with ferrocene. AB - Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach. PMID- 20584608 TI - Antimalarial 3-arylamino-6-benzylamino-1,2,4,5-tetrazines. AB - We report on novel 3-arylamino-6-benzylamino-1,2,4,5-tetrazines with potent activity against Plasmodium falciparum. PMID- 20584609 TI - Rational design of a novel peripherally-restricted, orally active CB(1) cannabinoid antagonist containing a 2,3-diarylpyrrole motif. AB - A new series of 2,3-diarylpyrroles have been prepared and evaluated as CB(1) antagonists. Modulation of the topological polar surface area allowed the identification of high affinity peripherally-restricted CB(1) antagonists. Compound 11, obtained after further optimization of the metabolic profile displayed very low brain penetration, yet was able to reverse CP55940-induced gastrointestinal transit inhibition following oral administration. PMID- 20584610 TI - Design and synthesis of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec 4-yl]-2-trifluoromethyl-benzonitriles as androgen receptor antagonists. AB - A novel series of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec-4-yl] 2-trifluoromethyl-benzonitriles has been synthesized. The ability of these compounds to act as antagonists of the androgen receptor was investigated and several were found to have potent activity in vitro and in vivo. PMID- 20584611 TI - N-Benzylsalicylthioamides as novel compounds with promising antimycotic activity. AB - The in vitro biological activity of N-benzylsalicylthioamides was evaluated against eight fungal strains by the broth microdilution method and the results were compared with those obtained with fluconazole. The compounds exhibited an in vitro antifungal activity against the fluconazole-susceptible as well as the fluconazole-resistant fungal strains. The biological activity was analyzed by quantitative structure-activity relationship (QSAR). PMID- 20584612 TI - The biomechanics of heel ulcers. AB - Heel ulcers are common, dangerous and costly, but their etiology is poorly understood and no biomechanical studies were conducted to explore it. This paper describes a biomechanical investigation of heel ulcers using a theoretical model that characterizes the internal mechanical loading at the soft tissues of a supported heel. The study is aimed first at identifying some heel-ulcer-specific risk factors pointed out by the biomechanical theory, and second, at demonstrating the kind of support that biomechanical theory and computer modeling can offer in the conduct of clinical studies in the pressure ulcer field. The modeling demonstrated that atypical foot anatomies characterized by heavy-weight foot, sharp posterior calcaneus and thin soft tissue padding are theoretically more prone to heel ulcers. Diabetes and edema at the feet were also predicted to impose risks for heel ulcers, which agrees very well with clinical observations. This paper therefore demonstrated that a biomechanical theory can be used to explain and interpret clinical and epidemiological findings related to heel ulcers. PMID- 20584613 TI - (-)-N-Formylanonaine from Michelia alba as a human tyrosinase inhibitor and antioxidant. AB - Tyrosinase is the first and rate limiting enzyme in the synthesis of melanin pigments for coloring hair, skin, and eyes. As reported in this study, a natural product, (-)-N-formylanonaine isolated from the leaves of Michelia alba D.C. (Magnolianceae), was found to inhibit mushroom tyrosinase with an IC50 of 74.3 microM and to have tyrosinase and melanin reducing activities in human epidermal melanocytes without apparent cytotoxicity to human cells, superior to the known tyrosinase inhibitors, such as kojic acid and 1-phenyl-2-thiourea (PTU). Based on homology modeling, the compound binds the active site by coordinating with two Cu2+ ions. In addition, the compound had antioxidation activities in tests for scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power, and chelating metal ions. To our knowledge, this is the first study to reveal the bioactivities of (-)-N-formylanonaine from this plant species. PMID- 20584614 TI - Delayed soft tissue recurrence after treatment of ameloblastoma in a black African: case report and review of the literature. AB - INTRODUCTION: Ameloblastoma is rare worldwide. Delayed treatment can result in significant morbidity from facial deformity and infiltration of adjacent tissues. Mortality can occur from invasion of vital structures in the head and neck, super infection, recurrent and even distant metastases. Recurrence after radical treatment is not common. CASE REPORT: This paper presents a case of soft issue recurrence in the chin 21 years after radical resection of the mandible for ameloblastoma. The iliac crest bone grafted to the site was not involved in the tumour recurrence. Conclusion. Radical surgical resection is accepted treatment for solid/multicystic ameloblastoma. However, the surgical review should be for life as recurrence can occur after a long interval. PMID- 20584615 TI - Estimation of the number of biophotons involved in the visual perception of a single-object image: biophoton intensity can be considerably higher inside cells than outside. AB - Recently, we have proposed a redox molecular hypothesis about the natural biophysical substrate of visual perception and imagery [1,6]. Namely, the retina transforms external photon signals into electrical signals that are carried to the V1 (striatecortex). Then, V1 retinotopic electrical signals (spike-related electrical signals along classical axonal-dendritic pathways) can be converted into regulated ultraweak bioluminescent photons (biophotons) through redox processes within retinotopic visual neurons that make it possible to create intrinsic biophysical pictures during visual perception and imagery. However, the consensus opinion is to consider biophotons as by-products of cellular metabolism. This paper argues that biophotons are not by-products, other than originating from regulated cellular radical/redox processes. It also shows that the biophoton intensity can be considerably higher inside cells than outside. Our simple calculations, within a level of accuracy, suggest that the real biophoton intensity in retinotopic neurons may be sufficient for creating intrinsic biophysical picture representation of a single-object image during visual perception. PMID- 20584616 TI - Cerebrospinal fluid u-plasminogen activator and matrix metalloproteinase-9 levels in human eosinophilic meningitis associated with angiostrongyliasis. AB - Cerebrospinal fluid (CSF) urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) levels were measured in patients with eosinophilic meningitis associated with angiostrongyliasis (EOMA) by quantitative sandwich enzyme immunoassays. The CSF concentrations of uPA and MMP-9 were evaluated in 30 EOMA patients and 10 controls. The CSF uPA and MMP-9 levels of the EOMA patients were significantly higher than those of the controls (p<0.001). The positive detection values were 73% (22/30) and 86.7% (26/30) for uPA and MMP-9, respectively. The uPA detection was in correlation with headache duration (p=0.008) and stiff neck (p=0.048), while the MMP-9 was in correlation with CSF total protein (p=0.006), CSF leukocytosis (p=0.004) and CSF eosinophil numbers (p=0.02). CSF uPA and MMP-9 levels are potentially useful for the understanding of immunologic pathogenesis, for therapeutic targets, for the diagnosis of EOMA and for monitoring treatment efficacy. PMID- 20584617 TI - p75NTR is an obligate signaling receptor required for cues that cause sympathetic neuron growth cone collapse. AB - The p75 neurotrophin receptor (p75NTR) is required for the activity of growth cone collapsing factors such as Nogo, MAG, OMgP, and ephrin A. Specifically, p75NTR associates with the Nogo receptor and GPI-linked ephrin A, and unliganded p75NTR mediates the biological effects of those proteins. Here we assess the requirement for p75NTR for the growth cone collapsing responses of semaphorins (Sema) 3A and 3F and ephrin B2 in sympathetic neurons. We show that the ability of Sema 3s or ephrin B2 to collapse growth cones is suppressed in p75NTR-/- sympathetic neurons. Ectopic expression of p75NTR restores the collapsing activity of Sema 3 in p75NTR-/- neurons. Moreover, p75NTR must be bound to its neurotrophin ligands to participate in Sema 3-mediated collapse. Ligand-bound p75NTR participates in Sema 3 and ephrin B2-mediated collapse via the Rho signaling pathway, since inhibition of Rho signaling is sufficient to suppress the effects of Sema 3s and ephrin B2 in p75NTR+/+ but not p75NTR-/- neurons. Our data suggest that in addition to its role as a co-receptor, p75NTR may provide an obligate parallel neurotrophin-activated inhibitory pathway that broadly sensitizes neurons to inhibitory cues. PMID- 20584618 TI - Left atrial dissection and intramural hematoma after aortic valve replacement. PMID- 20584619 TI - Isolated unilateral aplasia of submandibular gland: a rare anomaly detected incidentally on computerized tomography. AB - Aplasia of the major salivary glands is a very uncommon anomaly, with isolated aplasia of only 1 submandibular gland being even rarer. We report a case of a 60 year-old woman in whom unilateral aplasia of the left submandibular gland was detected incidentally on computerized tomography with no other associated congenital abnormalities. PMID- 20584620 TI - Autotransplantation of teeth: a procedure that gets no respect. PMID- 20584621 TI - Epigenetics in pain and analgesia: an imminent research field. AB - Heritable phenotypes resulting from environment-caused changes in a chromosome without alterations in the DNA sequence are increasingly recognized as a basis of personalized therapy. Epigenetic mechanisms include covalent modifications of the DNA (methylation) or of the DNA-packaging histones (e.g., deacetylation or phosphorylation). In addition, regulatory non-coding RNA molecules (micro-RNAs) exert epigenetic actions. This leads to disruption or otherwise modified expression of genes. Environmental influences such as nutritional factors, exposure to chemicals or drugs, but also social factors appear to exert epigenetic actions. Histone modifications and DNA methylation are associated with the subject's age. Epigenetic mechanisms can silence the expression of pro- or antinociceptive genes. To the epigenetic control of nociception adds its control of the pharmacodynamics or pharmacokinetics of analgesics by epigenetic control of drug targets and analgesics metabolizing enzymes. Although epigenetics-based strategies for pain therapy are not yet available, experiments in rodents suggest that RNA interference may become a new therapy approach for neuropathic and other pain. Another epigenetic approach to analgesic treatment employs inhibitors of histone deacetylase that act on the epigenome by indirectly remodeling the spatial conformation of the chromatin. Finally, epigenetic techniques such as RNA interference have been employed in pain research to proof the contribution of certain proteins to nociception. Thus, the new field of epigenetics becomes increasingly used in research and management of pain and will complement genetics. This article introduces epigenetics to pain and summarizes the current and future utility. PMID- 20584622 TI - Risk of pneumonia onset and discontinuation of oral intake following videofluorography in patients with Lewy body disease. AB - OBJECTIVE: We investigated the time course of pneumonia onset and duration of continued oral intake following videofluorography (VFG) in patients with Lewy body disease. PATIENTS AND METHODS: Subjects were 90 patients with idiopathic Parkinson's disease (IPD) and 45 with Lewy body dementia (LBD). We performed a follow-up study of the time from VFG until onset of pneumonia or discontinuation of oral intake, up to a maximum of 24 months, and determined the associated risk factors. We evaluated the cumulative rates of pneumonia onset and continued oral intake over 24 months for each disease. RESULTS: Among patients with Lewy body disease, 53 developed pneumonia and 21 discontinued oral intake; patients with aspiration fared significantly worse [hazard ratio (HR) = 26.62, 3.21, p < 0.01, = 0.05]. Hoehn-Yahr (HY) stage during VFG was also a risk factor for discontinuation of oral intake. The cumulative rate of pneumonia onset was significantly higher in the aspiration group for both IPD and LBD (p < 0.01, <0.01). The cumulative rate of continued oral intake tended to be lower in the aspiration group for IPD, and was significantly lower for LBD (p = 0.07, <0.01). CONCLUSION: Aspiration during VFG was a risk factor for pneumonia onset in patients with Lewy body disease. Aspiration and HY stage during VFG were risk factors for discontinuing oral intake. The cumulative rate of continued oral intake up to 24 months after VFG was poorest for LBD patients with aspiration. PMID- 20584623 TI - Probabilistic framework for tracking in artifact-prone 3D echocardiograms. AB - The analysis of echocardiograms, whether visual or automated, is often hampered by ultrasound artifacts which obscure the moving myocardial wall. In this study, a probabilistic framework for tracking the endocardial surface in 3D ultrasound images is proposed, which distinguishes between visible and artifact-obscured myocardium. Motion estimation of visible myocardium relies more on a local, data driven tracker, whereas tracking of obscured myocardium is assisted by a global, statistical model of cardiac motion. To make this distinction, the expectation maximization algorithm is applied in a stationary and dynamic frame-of-reference. Evaluation on 35 three-dimensional echocardiographic sequences shows that this artifact-aware tracker gives better results than when no distinction is made. In conclusion, the proposed tracker is able to reduce the influence of artifacts, potentially improving quantitative analysis of clinical quality echocardiograms. PMID- 20584624 TI - Analysis of causal models of diet for patients with head and neck cancer receiving radiation therapy. AB - PURPOSE: This study seeks to establish causal models of diet which maintain the appetite of head and neck cancer patients receiving radiation therapy. SAMPLE AND METHODS: We collected data from 208 patients at two radiation doses, 30/50 Gy, using a questionnaire on appetite and analyzed the items using structural equation modeling. RESULTS: In the causal model for 30 Gy, we established a path using the four intervening variables "ease of consuming foods in smooth forms," "ease of consuming foods with a chewable texture and suitable temperature," "ease of consuming lightly seasoned foods with a flavorful smell," and "overall ease of consuming a given meal" from the temporal relationship between "dietary preferences" and "maintaining appetite while caring for the oral cavity." In the causal model for 50 Gy, we established a path between "ease of consuming foods with a mild temperature and smell," and "maintaining appetite while caring for the oral cavity" using the four intervening variables "ease of consuming foods that are easy to swallow," "ease of consuming foods that dissolve well in the mouth," "ease of consuming foods with a mild taste," and "overall ease of consuming a given meal." The goodness of fit indices for both models were above 0.85 for both the goodness of fit index (GFI) and adjusted GFI (AGFI), and less than 0.08 for root mean square error of approximation (RMSEA), indicating a satisfactory goodness of fit. CONCLUSIONS: Food characteristics help to maintain patient appetite at cumulative radiation doses of 30/50 Gy. PMID- 20584625 TI - Cultural interrelationships and the lived experience of Pakistani breast cancer patients. AB - AIM: There is a paucity of British and international literature on the psychological, sociological and cultural correlates of breast health in ethnic minority women. METHODS: This two centre qualitative study was part of a larger study that aimed to examine the influence of culture on the lived experience of Pakistani Muslim breast cancer patients. Thirty six patients attending hospital out-patient breast cancer clinics in Lahore, Pakistan and London, UK were recruited to the study. Women were predominantly married, 20-76 years of age with an average of three children. Semi-structured interviews were undertaken. Interview data were analysed using thematic analysis. RESULTS: Five themes emerged: Discovery and reaction to the disease; disclosure to family; developing emotions; emerging reality; long term uncertainty. CONCLUSIONS: Data infer that irrespective of city of residence, the cultural attributes of women, breast health awareness and reactions to the diagnosis and treatment are similar. To raise awareness, more focused health education interventions are needed. PMID- 20584626 TI - Improvements in physical and mental health following a rehabilitation programme for breast cancer patients. AB - PURPOSE: To investigate how breast cancer patients referred to in-patient rehabilitation at Mosseberg Rehabilitation Centre (MRC) in Sweden perceive their life situation, and if their life satisfaction and mental health have changed three months later. METHOD: This prospective study is based on 46 women, all of them in working age. Three validated questionnaires were used, the Life Satisfaction (Li-Sat 11) scale, the Maastricht Questionnaire and the Shirom Melamed Burnout Questionnaire (SMBQ). RESULTS: Statistically significant improvements for the variables physical and mental health were seen in the measurements made using the Li-Sat 11 scale. The SMBQ survey showed a statistically significant improvement in the composite results for the indices involved. Likewise, the Maastricht Questionnaire showed statistically significant improvements in health status with respect to feelings of exhaustion and fatigue. CONCLUSION: More effective treatments have resulted in an increase in the number of breast cancer survivors and in the demand for rehabilitation. This study shows improvements in health and satisfaction with health, but cannot conclude this result as only an effect of the rehabilitation programme. Since only a few studies have until now shed light on the benefits of in-patient rehabilitation following a breast cancer diagnosis, there is an urgent need for continued research in this area. PMID- 20584627 TI - An exploration of public knowledge of warning signs for cancer. AB - BACKGROUND: Warning signs of cancer have long been used as an effective way to summarise and communicate early indications of cancer to the public. Given the increasing global burden of cancer, the communication of these warning signs to the public is more important than ever before. AIM: This paper presents part of a larger study which explored the attitudes, knowledge and behaviours of people in mid-life towards cancer prevention. The focus of this paper is on the assessment of the knowledge of members of the public aged between 35 and 54 years of age. METHOD: A questionnaire was administered to a representative sample of the population listing 17 warning signs of cancer. These included the correct warning signs and distracter signs. Respondents were asked to correctly identify the seven warning signs. RESULTS: Findings show that respondents could identify 4.8 cancer warning signs correctly. Analysis by demographics shows that being female, being older, having a higher level of educational attainment and being in a higher socio-economic group are predictors of better level of knowledge of cancer warning signs. RECOMMENDATIONS: Recommendations are proffered with regard to better targeting, clarification and communication of cancer warning signs. PMID- 20584628 TI - Colorectal cancer follow-up: patient satisfaction and amenability to telephone after care. AB - PURPOSE: To explore patient satisfaction on different aspects of follow-up service provision following treatment for colorectal cancer and amenability to an alternative strategy for follow-up care. METHODS AND SAMPLE: A postal survey was administered to 297 eligible patients who had been treated for colorectal cancer at a large hospital in the North West of England. Patients were asked to indicate responses to questions comprising likert scales, including views on organisation of care, information and advice, personal experience of care, satisfaction with information and care, views on specialist nursing services and amenability to telephone follow-up. KEY RESULTS: One hundred and eighty-seven completed surveys were returned (62.97% response rate). Analysis of scale data indicated high levels of satisfaction on all outcome measures but sub-optimal rates of satisfaction on some items. Respondents indicated high levels of satisfaction with information related to disease and treatment but lower levels of satisfaction for items related to genetic risk, sexual attractiveness and self care. Colorectal nurse specialists were highly rated, especially in terms of information provision and personal experience of care. Patients were generally amenable to telephone follow-up, although male patients indicated higher levels of willingness to accept this approach than females. CONCLUSIONS: Satisfaction with traditional medical based follow-up is generally high in this patient cohort but there is room for improvement in terms of service delivery. High levels of satisfaction with the care delivered by colorectal nurse specialists and patient acceptance of telephone follow-up suggests nurse-led telephone follow-up is a viable alternative to traditional hospital based follow-up. PMID- 20584629 TI - Understanding sexuality in women with gynaecological cancer. AB - PURPOSE: To develop a better understanding of the term "sexuality" in the context of gynaecological cancer and to examine the applicability of Woods (1987) conceptual framework of sexuality when examining changes in sexuality following a gynaecological cancer diagnosis. METHODS: A comprehensive search for literature focusing on sexuality in gynaecological cancer patients, published in English from 1998 to 2009, was performed in the electronic databases CINAHL, Pubmed and ISI Web of Knowledge. KEY RESULTS: Results revealed that a lack of conceptual frameworks exist which aim to describe the concept of sexuality in cancer care. In addition, a greater emphasis exists in the literature on the physical aspect of sexual functioning with a neglect of other broader dimensions. However, Woods (1987) proposes a holistic view of sexuality which is composed of three inter related dimensions 1) Sexual Function 2) Sexual Self Concept and 3) Sexual Relationships. Through the examination of empirical literature surrounding sexuality in a gynaecological cancer context, this framework was further developed to create a neo-theoretical framework of sexuality. CONCLUSIONS: The main conclusion that can be drawn from this review of the literature is that sexuality is a multidimensional construct and must be assessed in this way. The neo theoretical framework of sexuality provides a holistic view towards sexuality which is lacking in the literature surrounding sexuality in the female cancer care context. Healthcare professionals could use this holistic approach when providing information and support to patients with gynaecological cancer. PMID- 20584630 TI - Anti-allergic potential of oligomannose-coated liposome-entrapped Cry j 1 as immunotherapy for Japanese cedar pollinosis in mice. AB - Administration of oligomannose-coated liposomes (OMLs) in mice can induce Th1 immune responses against antigens entrapped in the OMLs. In the present study, we investigated the anti-allergic effect of treatment with oligomannose-coated liposomes (OMLs) with entrapped Cry j 1, a major allergen of Japanese cedar pollen (Cry j 1/OMLs), in Balb/c mice sensitized with Cry j 1. Pretreatment of unsensitized mice with Cry j 1/OMLs repressed the elevation of total and allergen specific IgE levels in sera elicited in response to subsequent sensitization with Cry j 1. Cry j 1-specific IgG1 in sera also decreased in Cry j 1/OML-treated mice, while the levels of Cry j 1-specific IgG2a in these mice significantly increased after sensitization with Cry j 1. In addition, Cry j 1/OML-treated mice showed high IFN-gamma production from spleen cells and low IL-4/IFN-gamma and IL 5/IFN-gamma ratios in response to in vitro stimulation with Cry j 1. These results indicate that allergen-specific Th1 immune responses predominate over Th2 responses and control IgE elevation in Cry j 1/OML-treated mice. The anti allergic effect of Cry j 1/OML determined by suppression of serum IgE levels was also observed in Cry j 1-presensitized mice after challenge with antigen. Thus, Cry j 1/OMLs may be useful for immunotherapeutic control of allergic reactions to Japanese cedar pollinosis. PMID- 20584631 TI - Negative modulation of invariant natural killer T cell responses to glycolipid antigens by p38 MAP kinase. AB - Invariant natural killer T (iNKT) cells are CD1d-restricted, glycolipid-reactive lymphocytes with potent immunoregulatory characteristics. Although recent years have witnessed intensified interest in iNKT cells, little is known about intracellular signaling pathways that control iNKT cell responses, including those mediated by mitogen-activated protein kinases (MAPKs). We employed selective inhibitors of ERK1/2, JNK and p38 to examine the importance of these MAPKs in iNKT cell responses to the prototype glycolipid antigen alpha galactosylceramide (alpha GC). Activation of DN32.D3 iNKT cells in the presence of PD98059 led to decreased interleukin (IL)-2 production, indicating a role for ERK in mouse iNKT cell responses. In contrast, addition of the JNK inhibitor SP600125 to cultures did not significantly affect cytokine production, suggesting that JNK is not critically needed for iNKT cell responses. Interestingly, selective inhibition of p38 by either SB203580 or SK&F 86002 resulted in augmented IL-2 production by DN32.D3 cells after stimulation with alpha GC. This was also evident when iNKT cells were stimulated with an anti-CD3 monoclonal antibody thus bypassing the requirement for CD1d-mediated antigen presentation, indicating that p38 inhibition affects signal transduction downstream of iNKT cells' T cell receptors. Primary splenic iNKT cells similarly exhibited enhanced cytokine response to alpha GC when cultured in the presence of p38 inhibitors. Importantly, in vivo administration of SB203580 resulted in higher IL-4 and interferon-gamma secretion in alpha GC-treated mice. These results demonstrate that MAPKs play distinct signaling roles in iNKT cells and that both in vitro and in vivo iNKT cell responses to glycolipid antigens can be negatively modulated by p38. PMID- 20584632 TI - Risks associated with exercise testing and sports participation in cystic fibrosis. AB - BACKGROUND: Severe adverse reactions (SARs) associated with physical exercise have not been systematically studied in cystic fibrosis (CF). METHODS: Two surveys were conducted to assess the incidence of exercise-related SARs: a caregiver survey asking for complications associated with exercise testing and in hospital training therapy and a web-based patient survey asking for problems with exercise. RESULTS: 78 of 107 CF facilities caring for 4208 patients responded to the caregiver survey, 256 patients answered the web-based survey. No SARs were reported for 713 exercise tests. With in-hospital training, the yearly incidence of exercise-related SARs such as pneumothorax, cardiac arrhythmia, injury or hypoglycaemia was <1% each, the respective lifetime incidences reported by the patients were 0.8-6.3%. 67% of the patients reported no SARs with exercise. CONCLUSIONS: Exercise testing is safe in patients with CF. Despite the limitations in quality of data, the incidence of exercise-related SARs appears low in this population. PMID- 20584633 TI - Application of antimicrobial polypeptide host defenses to aquaculture: Exploitation of downregulation and upregulation responses. AB - Antimicrobial polypeptides (AMPPs), consisting of peptides and small proteins with antimicrobial activity, are an integral component of innate immunity. Their often potent properties and widespread prevalence in fish suggests that designing means of manipulating their levels has considerable potential for maintaining or improving fish health. There is evidence that a number of chronic stresses lead to significant downregulation of AMPPs and thus their monitoring could be a highly sensitive measure of health status and risk of an infectious disease outbreak. Conversely, upregulation of AMPP expression could be used to enhance disease resistance in stressful environments, as well as improve the efficacy of traditional antimicrobial drugs. However, further work is required in linking levels of a number of AMPPs to physiological function since, while a number of studies have documented the down- or upregulation of AMPPs via gene expression, relatively few studies have quantitatively examined changes in protein expression. In addition, not all AMPPs appear to be expressed at microbicidal levels in vivo, suggesting that at least some may have functions other than being directly protective. Nonetheless, in fish, there is evidence that some constitutively expressed AMPPs, such as piscidins and histone-like proteins, are expressed at microbicidal levels and that they decline with stress. Furthermore, certain AMPPs derived from hemoglobin-beta are upregulated to microbicidal levels after experimental challenge. The likely widespread distribution of these three AMPP groups in fish provides the opportunity to design strategies to greatly improve the health of cultured fish populations. PMID- 20584634 TI - Single twin demise: consequence for survivors. AB - Multiple pregnancies, the majority of which are twins, are at substantially higher risk of fetal morbidity and mortality when compared with singleton pregnancies. Single fetal demise occurs in up to 6.2% of all twin pregnancies. It may cause considerable risk for the co-twin including increased risk of fetal loss, premature delivery, neurovascular injury and end-organ damage. In this review we seek to summarise the most contemporary literature on the aetiology of single twin demise, the pathophysiology of injury to the surviving twin and the evidence for current management strategies. PMID- 20584635 TI - A rare case of congenital ulcerated subcutaneous fat necrosis of the newborn. PMID- 20584636 TI - Metastatic implantation squamous cell carcinoma in a split-thickness skin graft donor site. AB - We present the case of a patient who developed a possible implantation metastatic squamous cell carcinoma (SCC) at a donor site 2 months following split-thickness skin graft (STSG) harvesting. This case highlights implantation of malignant cells from a contaminated hollow needle as a mechanism of spread to skin graft donor sites and offers an important learning point in the practice of local anaesthetic cutaneous cancer surgery. PMID- 20584637 TI - Acquired atrial septal defects secondary to rupture of the atrial septum in dogs with degenerative mitral valve disease. AB - Acquired atrial septal defects (ASDs) secondary to atrial septal rupture are uncommon in dogs with degenerative mitral valve disease. Echocardiographic diagnosis of these defects has not previously been described. The echocardiographic features in two cases identified antemortem are presented in this report. ASDs can be difficult to identify on two-dimensional echocardiogram when relatively small in size and may be underreported. Acquired ASDs may alter the physiology, treatment plan and prognostic implications for the dogs in which they occur and their presence should be considered in all cases of degenerative mitral valve disease that develop signs of right-sided heart failure. PMID- 20584638 TI - [Expression of TGF-beta1 and E-cadherin in primary and metastatic ovarian carcinoma]. AB - OBJECTIVE: To detect the expression of the protein of TGF-beta1 and E-cadherin in the primary and metastatic lesions of ovarian carcinoma and explore the mechanism of the metastasis of ovarian carcinoma. METHODS: Immunohistochemistry (IHC) was performed to detect the expression of TGF-beta1 and E-cadherin proteins in primary and metastatic ovarian carcinoma, benign epithelial ovarian tumor and normal ovarian tissue. RESULTS: The expression of TGF-beta1 was significantly higher in ovarian carcinoma (67.2%) than in benign tumors (28.6%) and normal ovarian tissue (18.9%) (Chi2=26.94, P<0.001), but E-cadherin expression showed a reverse pattern. TGF-beta1 expression in the primary ovarian carcinoma carcinoma was associated with the FIGO stage, lymph metastasis and ascites of the tumor (P=0.01, P=0.01, and P=0.04, respectively). E-cadherin expression in the tumor was associated with the differentiation (P=0.02) and lymph metastasis of ovarian carcinoma (P=0.04). The expressions of TGF-beta1 and E-cadherin were all significantly lower in the primary tumors than in the metastatic tumor (Chi2=4.70, P=0.03; Chi2=5.91, P=0.015). A significant correlation was found between the expressions of the TGF-beta1 and E-cadherin in the primary carcinoma (Kappa value of -0.32, P=0.01). CONCLUSION: TGF-beta1 and E-cadherin are closely associated with the metastasis of ovarian carcinoma and might be potential targets for controlling the metastasis of ovarian carcinoma. PMID- 20584639 TI - [Expression and antibody preparation of FKBP38 and its application]. AB - OBJECTIVE: To obtain recombinant N-and C-terminal of FKBP38 and prepare anti FKBP38 polyclonal antibody for Western blotting (WB), immunohistochemical (IHC) and immunofluorescence (IF) analyses. METHODS: The N-terminal (1-207 aa) and C terminal (209-387 aa) cDNA of FKBP38 were sub-cloned from the full-length cDNA of FKBP38 and ligated to prokaryotic expression plasmid pGEX-6P-1 for construction of the recombinant vectors pGEX-6P-1-FKBP38-N and pGEX-6P-1-FKBP38-C. After sequencing, the recombinant vectors were transformed into E.coli BL21 and GST tagged FKBP38-NT and FKBP38-CT were induced by IPTG. The proteins were purified by Glutathione affinity chromatography column and characterized by SDS-PAGE. Rabbits were immunized with the purified recombinant protein to prepare the antiserum, which were analyzed by WB, IHC and IF. RESULTS: The recombinant vectors pGEX-6P-1-FKBP38-N and pGEX-6P-1-FKBP38-C were successfully constructed. After IPTG induction, the E.coli transformed with these plasmids expressed GST tagged protein, which was successfully purified. Western blotting demonstrated that the purified antibody could specifically bind to FKBP38 in various cell lines. Immunofluorescence assay showed that FKBP38 was located mainly on the mitochondria. Immunohistochemical analysis revealed cytoplasmic location of FKBP38 in breast cells. CONCLUSION: We successfully expressed and purified N- and C-terminal of FKBP38, and FKBP38 polyclonal antibody we prepared can specifically recognize FKBP38 in SB, IF and IHC assays, which facilitates further functional investigation of FKBP38. PMID- 20584640 TI - [Inhibitory effect of photodynamic therapy combined with paclitaxel on the proliferation of esophageal carcinoma Eca-109 cells]. AB - OBJECTIVE: To investigate the inhibitory effect of photodynamic therapy (PDT) in combination with paclitaxel (PCT) on proliferation in esophageal carcinoma Eca 109 cells line. METHODS: Eca-109 cells were treated with PCT alone, HPD alone at different doses, or their combinations. For the combined treatments, the cells were exposed to PCT for 12 h followed by incubation with HPD at high, middle or low concentrations for 4 h. PDT was then performed on these treated cells and fluorescence microscopic observation was made before and after PDT. The cell survival was measured by MTT assay, and the cell apoptosis rate analyzed by flow cytometry after a 24-h cell incubation following PDT. RESULTS: The fluorescence excitation of the cells was weakened after PDT. Combined treatments resulted in significantly lowered cell survival rate and increased cell apoptosis rates as compared to those of the control cells and the cells treated with PCT alone and low-dose HPD (P<0.01). Significant differences were also noted among the cells exposed to HPD at different concentrations (P<0.05). CONCLUSION: PDT combined with PCT have significant synergetic effects in inhibiting the proliferation of human esophageal carcinoma cells and inducing their apoptosis in vitro. PMID- 20584641 TI - [Effects of exercise on expression and phosphorylation of PI3K and PKB in insulin signaling in the skeletal muscles of type 2 diabetic rats]. AB - OBJECTIVE: To investigate the effect of exercise on the expressions of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (PKB) phosphorylation, protein and glucose transport proteins (GLUT4) at both the protein and mRNA levels in the skeletal muscles of type 2 diabetic rats. METHODS: Thirty male SD rats were randomly divided into control group with normal diet feeding, diabetic group and diabetic exercise group with high-fat diet feeding. After 8 weeks of the high-fat diet, each rat received an intraperitoneal injection of streptozotocin (STZ, 30 mg/kg). Three weeks after the injection, the rats were rated for the presence of diabetes, and the rats in the exercise groups took swimming training for 4 weeks; all the groups maintained their assigned diets. The gastrocnemius of all the rats were dissected 48 h after the last training session. Western blotting was applied to detect the phosphorylation and protein expression of PI3K and PKB and the protein expression of GLUT4. The expression of GLUT4 mRNA was determined by RT-PCR. RESULTS: Compared with the diabetic group, the diabetic rats in the exercise group showed significantly increased protein expression and phosphorylation of PKB (P<0.05) and elevated GLUT4 protein and mRNA expressions in the skeletal muscles (P<0.01, P<0.05). CONCLUSION: Exercise training can modulates insulin signal transduction through the protein expression and phosphorylation of the protein kinase to promote glucose uptake in the skeletal muscle of type 2 diabetic rats. PMID- 20584642 TI - [Effects of sodium butyrate on acetylation of histone in gamma-globin gene promoter regions in K562 cells: a study using chromatin immunoprecipitation]. AB - OBJECTIVE: To develop a real-time PCR-based chromatin immunoprecipitation (ChIP) assay for determining the effect of sodium butyrate on acetylation of histone in gamma-globin gene promoter regions in K562 cells. METHODS: K562 cells were grown in the presence or absence of 0.5 mmol/L sodium butyrate for 48 h, and 1=10(7) cells per group were used for real-time PCR-based ChIP with anti-acetylated histone H3 or H4 antibodies. The levels of acetylated histone H3 and H4 (acH3 and acH4) in Ggamma- and Agamma-globin gene promoter regions were measured. RESULTS: In the K562 cells with sodium butyrate treatment or without any treatment, the levels of acH3 or acH4 in Ggamma- or Agamma-globin gene promoter were higher than that in the necdin gene (negative control). Compared with the untreated K562 cells, the cells treated with 0.5 mmol/L sodium butyrate showed a 3.1-fold or 2.6 fold increase in acH3 or acH4 in Ggamma-globin gene promoter region, with also a 3.7-fold or 3.2-fold increase in acH3 or acH4 in Agamma-globin gene promoter region, respectively (P<0.01). CONCLUSION: We have successfully developed a real time PCR-based ChIP assay for analyzing the acetylation of histone H3 and H4 in gamma-globin gene promoter regions. Our results support the role of sodium butyrate in increasing the level of acetylated histone in gamma-globin gene promoter regions. PMID- 20584643 TI - [Forward genetic screening for zebrafish mutants defective in myelopoiesis]. AB - OBJECTIVE: To identify zebrafish mutants with myelopoiesis defects by ENU mutagenesis and large-scale forward genetic screening. METHODS: Male zebrafish were mutagenized with N-ethyl N-nitrosourea to induce mutations in the spermatogonial cells to generate the founders, which were outcrossed with AB to raise F1 fish. The F1 fish from different founders were mated to generate the F2 families. The F3 embryos from F2 sibling crosses were screened by Sudan black B staining and neutral red staining. RESULTS: A total of 350 F2 families from F1 sibling crosses were screened, and 1424 F2 crosses were analyzed. Six mutations were identified resulting in abnormal Sudan black B staining and neutral red staining, indicating the involvement of neutrophil deficiency or macrophage abnormalities. CONCLUSION: It is simple and cheap to induce and screen myelopoiesis deficiency in zebrafish by ENU chemical mutagenesis and Sudan black B staining and neutral red staining. These mutants shed light on the identification of the genes important to myelopoiesis in zebrafish. PMID- 20584644 TI - [Clinical features of panereatic disease-associated portal hypertension]. AB - OBJECTIVE: To investigate the clinical features and management of pancreatic disease-associated portal hypertension. METHODS: A retrospective analysis was carried out in patients with portal hypertension and concurrent pancreatic diseases. The medical records of these patients were reviewed including the data of demographics, etiologies, venous involvement, clinical presentations, laboratory tests, imaging studies, therapeutic modalities and outcomes. RESULTS: Fifty-two patients with portal hypertension resulting from pancreatic diseases were found in our hospital, accounting for 4% of all the patients with portal hypertension in 11 years. The underlying pancreatic diseases were chronic pancreatitis (21 cases, 35.6%), pancreatic carcinoma (20 cases, 33.9%), acute pancreatitis (8 cases, 13.6%), pancreatic pseudocyst (3 cases, 5.1%). Of the 40 patients whose venous involvement was identified, splenic vein obstruction occurred in 27 cases (67.5%) and portal vein obstruction in 16 cases (40.0%). Mild or moderate splenomegaly was present in 48 cases (81.4%), with leukocytopenia as the most common manifestation of the 31 cases (52.5%) with concomitant hypersplenism. Forty-five patients (76.3%) developed gastroesophageal varices (including 35 with isolated gastricvarices), and among them 22 experienced bleeding (42.3%). Conservative treatment was effective in controlling acute bleeding, but could not prevent re-bleeding. Splenectomy was performed in 18 patients mainly due to gastrointestinal hemorrhage. No postoperative bleeding occurred during the follow-up ranging from 8 months to 9 years. CONCLUSION: Pancreatic diseases may compromise portal vein and its tributaries, leading to generalized or regional portal hypertension. Pharmacological therapy can effectively control acute variceal bleeding, while surgical treatment is the appropriate procedure of choice in case of hemorrhagic recurrence. PMID- 20584645 TI - [Cerebral blood flow, cerebral blood volume, oxygen utilization and oxygen extraction fraction: the influence of age]. AB - OBJECTIVE: To analyze the changes of cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen utilization (CMRO2) and oxygen extraction fraction (OEF) with age. METHODS: The PET images of 7 young (21.0-/+1 years old) and 7 aged volunteers (60.9-/+4.7 years old) were analyzed to identify the areas where CBF, CBV, CMRO2, OEF had significant differences with age. The images were anatomically normalized by statistical parametric mapping (SPM2). A voxel by voxel calculation was performed to obtain the slope with age. Voxels which had statistically significant differences (P<0.05) with age were shown both on global and ROIs brain images. RESULTS: The CBF decreased with age as was consistent with previous reports. The age-related changes in CBV and CMRO2 were similar to CBF, but OEF increased with age. CONCLUSION: CBF, CBV and CMRO2 generally decline with age. The increase in OEF with age suggests a greater reduction in CBF than in CMRO2. The most significant decreases of CBF and CMRO2 occur in the convexity of the frontal cortex and inferior parietal cortex in all the functional images, while in the white matter, the influence of age is minimal. PMID- 20584646 TI - [Expression, purification and bioactivity evaluation of streptavidin-tagged human interleukin-21 fusion protein]. AB - OBJECTIVE: To obtain streptavidin-tagged human interleukin-21 (hIL21) fusion protein and evaluate its bioactivities. METHODS: hIL21-SA-pET21 and pET24a-SA- hIL21 plasmids were constructed and expressed in BL21(DE3) host bacteria. The hIL21-SA and SA- hIL21 fusion protein were purified through Ni-NTA affinity chromatography and refolded by dialysis. Flow cytometry was used to detect hIL21 SA and SA- hIL21 fusion protein on the biotinylated MB49 tumor cells. MTT assay was used to evaluate the effect of the fusion protein on the proliferation of human peripheral blood lymphocytes (PBLs) stimulated by Anti-CD3. RESULTS: The recombinant fusion proteins were highly expressed in BL21(DE3) at about 30% of the total bacterial proteins. The two fusion proteins exhibited bifunctional activities, i.e. both biotin-binding property and hIL21 activity and SA-mediated high-affinity binding to biotinylated cell surfaces (with anchoring modified rate of about 95.18% and 96.91%). CONCLUSION: We have successfully obtained bifunctional fusion protein hIL21-SA and SA- hIL21,which will provide a basis for further study of tumor biotherapy using the proteins. PMID- 20584647 TI - [Changes of neurotransmitter endothelin, thromboxance B2 and 6-keto-prostaglandin F1 alpha in patients with chronic pulmonary heart disease]. AB - OBJECTIVE: To explore the changes of the neurotransmitters in patients with chronic pulmonary heart disease (CPHD) and its clinical significance. METHODS: Seventy-two patients with CPHD (42 males, 30 females, mean age 55.6-/+8.9 years) were enrolled in the study, including 48 patients with compensated CPHD and 24 with uncompensated CPHD. Plasma endothelin (ET), thromboxance B2 (TXB2) and 6 keto-prostaglandin F1 alpha (6-K-PGFlalpha) were detected by radioimmunoassay. Thirty blood donors were selected as the normal control. RESULTS: Compared with the normal controls, CPHD patients showed abnormal pulmonary function, and significantly elevated levels of plasma ET and TXB2 (P<0.01) and lowered 6-K PGFlalpha(P<0.01), but no significant differences were found between the patients with compensated CPHD and uncompensated CPHD (P>0.05). Plasma ET and TXB2 levels were inversely correlated to 6-K-PGFlalpha level (r=-0.4571, P<0.05). CONCLUSION: The patients with CPHD present with obvious changes of plasma ET, TXB2 and 6-K PGFlalpha. PMID- 20584648 TI - [Relation between insulin resistance and glutamic acid decarboxylase antibody titers in latent autoimmune diabetes in adults]. AB - OBJECTIVE: To investigate the relation between insulin resistance and glutamic acid decarboxylase antibody (GAD-Ab) titers in latent autoimmune diabetes in adults (LADA). METHODS: The patients with phenotypic type 2 diabetes were screened for GAD-Ab positivity, and the 141 positive patients were divided into two subgroups according to the GAD-Ab titer, namely the high-titer group (LADA-1 subtype) and low-titer group (LADA-2 subgroup). The clinical features and insulin resistance were compared between the two groups. Insulin resistance was calculated by HOMA 2 software, and GAD-Ab and C peptide were determined with radioligand and radioimmune assay, respectively. RESULTS: Compared with low-titer LADA patients, the patients with high titers had younger age of onset, lower BMI, higher HbA1c level, and worse fasting and postprandial C peptide levels. The insulin resistance index by HOMA 2 was significantly lower in LADA-1 group than in LADA-2 group (1.6-/+1.1 vs 2.1-/+1.1, P=0.001). The HOMA2-IR index showed a negative correlation to GAD-Ab titer. CONCLUSION: The degree of insulin resistance is correlated to GAD-Ab titers in LADA, and low titer patients have higher insulin resistance level. PMID- 20584649 TI - [Mechanisms of foam cell formation in smooth muscle cell derived from bone marrow stem cells]. AB - OBJECTIVE: To establish a model of smooth muscle cells differentiated from bone mesenchymal stem cells (BMSC-SMCs) in vitro and explore the relationship between scavenger receptors A (SR-A) and caveolin-1. METHODS: BMSCs were isolated from the femoral bone of SD rats by adherent culture. After treatment of the BMSC-SMCs with 80 mg/L ox-LDL for 72 h, Western blotting was performed to detect the expression of scavenger receptor SR-A, cell cholesterol transport protein ATP binding cassette transporter Al (ABCA1) and caveolin-1. RESULTS: BMCS-SMCs became foam cells after treatment with ox-LDL. BMSC-SMC gave rise to more foam cell formation than VSMCs did. Western blotting showed that treatment with 80 mg/L ox LDL for 72 h resulted in significantly increased expression of SR-A and significantly decreased expressions of ABCA1 and caveolin-1. CONCLUSIONS: Treatment of BMCS-SMCs with ox-LDL results in cholesterol ester accumulation in the cells to result in foam cells, the mechanism of which involves up-regulation of scavenger receptor SR-A expression and down-regulation of the reverse cholesterol transport protein ABCA1 and caveolin-1 expression. PMID- 20584650 TI - [Short hairpin RNA targeting N-acetylglucosaminyltransferase V inhibits the proliferation of prostate cancer PC-3 cell line]. AB - OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) targeting N acetylglucosaminyltransferase V (GnT-V) on the proliferation of prostate cancer PC-3 cells. METHODS: Lipofectamine 2000 was used to transfect the recombinant plasmids carrying the shRNA targeting GnT-V gene into PC-3 cells. Semi quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of GnT-V, and CCK-8 assay was used to measure the cell proliferation after the transfection. RESULTS: The recombinant plasmids were successfully transfected into PC-3 cells, resulting in a reduction of GnT-V mRNA expression by 73%. The proliferation of PC-3 cells was significantly inhibited after the transfection. CONCLUSION: The shRNA targeting GnT-V gene can reduce the expression of GnT-V mRNA and inhibit the proliferation of PC-3 cells in vitro. PMID- 20584651 TI - [Quantitative determination of podophyllotoxin in dermal and blood microdialysis samples of rats by liquid chromatography-tandem mass spectrometry]. AB - OBJECTIVE: To develop and validate a sensitive method for quantitative analysis of podophyllotoxin in blood and dermal microdialysis samples of rats based on liquid chromatography-tandem mass spectrometry (UFLC-MS-MS). METHODS: The microdialysis samples were prepared by liquid-liquid extraction using ethyl acetate with etoposide as the internal standard (IS). Podophyllotoxin was separated with an Agilent ZORBAX XDB-C18 column (2.1 mmx50 mm, 3.5 microm). The mobile phase consisted of acetonitrile: 10 mmol/L ammonium acetate (40:60, V/V) at a flow rate of 0.3 ml/min and the analysis was performed at the ambient temperature. The UFLC-MS/MS system was operated in the mode of multiple reaction monitoring using the electrospray ionization technique in positive mode. RESULTS: Podophyllotoxin and etoposide responses were optimized at the transitions m/z 432.7-->397.3 and 589.5-->229.5, respectively. Calibration curves were linear over the range 2.0-1000 ng/ml. The lowest limits of quantification and detection values were 2.0 ng/ml and 0.7 ng/ml, respectively. The inter- and intra-day precision and accuracy were both less than 15%. CONCLUSION: This selective and sensitive method can be used to quantity podophyllotoxin in the blood and dermal microdialysates of rats. PMID- 20584652 TI - [Effects of SiRNA-EGFR on the expression of hyaluronidase gene EGFR in human breast cancer cells]. AB - OBJECTIVE: To study the effect of SiRNA-EGFR on the expression of hyaluronidase gene in human breast cancer cells. METHODS: Reverse transcription-polymerse chain reaction was used to detect the changes in the expression of EGFR mRNA in human breast cancer cell lines MDA-MB-231, MDA-MB-435S, ZR-75 and ZR-75-30 after transfection by SiRNA-EGFR. RESULTS: After transfection with SiRNA-EGFR, the expression levels of EGFR were significantly inhibited in MDA-MB-231, MDA-MB 435S, ZR-75 and ZR-75-30 cells (P<0.05). CONCLUSION: Transfection by SiRNA-EGFR can inhibit the expression of EGFR mRNA in human breast cancer cells. PMID- 20584653 TI - [Technical optimization for extracting hypotensive active peptides from Agrocybe aegerita]. AB - OBJECTIVE: To optimize the techniques for extracting hypotensive active peptides from Agrocybe aegerita. METHODS: The effects of the liquid/solid ratio, extraction time and temperature, pH value of the initial liquid on the extraction percentage (EP) of the hypotensive active peptides were investigated, and inhibition percentage (IP) of the extracts on angiotensin I-converting enzyme was determined. RESULTS: Optimal extraction of the hypotensive active peptides from Agrocybe aegerita was achieved with the liquid/solid ratio of 40:1, extraction time of 3 h, extraction temperature at 30 degrees Celsius;, and pH=8 of the initial liquid. The EP of the hypotensive active peptides from Agrocybe aegerita could reach 87.7% with IP of the extracts on angiotensin I-converting enzyme of 54.0%. CONCLUSION: This method is simple and efficient for extracting hypotensive active peptides from Agrocybe aegerita. PMID- 20584655 TI - [Evaluation of continuous venous-venous hemofiltration combined with coupled plasma filtration adsorption for treatment of systemic inflammation response syndrome with acute renal failure]. AB - OBJECTIVE: To evaluate the clinical efficacy of continuous venous-venous hemofiltration (CVVH) combined with coupled plasma filtration adsorption (CPFA) in the management of systemic inflammation response syndrome (SIRS) complicated by acute renal failure (ARF). METHODS: Thirty patients with SIRS complicated by ARF (including 25 with severe acute pancreatitis, 2 with colonic perforation with infection, and 3 with acute infective endocarditis) were randomly divided into CVVH plus CPFA group (n=14) and CVVH alone group (n=16). The APACHE II score, mean arterial pressure, PaO2/FiO2, TNF-alpha and IL-10 were detected prior to or after the intervention. The feasibility and tolerance of CVVH plus CPFA and the therapy-related adverse reactions were evaluated. RESULTS: The two groups showed no significant differences in the baseline clinical characteristics (P>0.05). The mean arterial pressure and PaO2/FiO2 increased significantly after treatment as compared with the control (P<0.05), with TNF-alpha being reduced and IL-10 elevated. In CVVH plus CPFA group, APACHEII score improved significantly after 10 days (P<0.05). No therapy-related adverse reactions were noted, suggesting good tolerance of CVVH plus CPFA. CONCLUSION: CVVH combined with CPFA is an effective and safe method for improving the clinical outcome of patients with SIRS and ARF. PMID- 20584654 TI - [Protective effect of puerarin against calcium overload after focal cerebral ischemia injury in rats]. AB - OBJECTIVE: To observe the temporal and spatial changes in the distribution of Ca2+ in the rat brain following focal cerebral ischemia injury and explore the protective effect of puerarin against calcium overload. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion in rats. After cerebral ischemia, puerarin was administered in the rats at different time points. The volume of ischemic cerebral tissue was assessed by TTC staining, and the fluorescence intensity of Ca2+ in the cortex and corpora striata was determined under laser scanning confocal microscope. RESULTS: The fluorescence intensity of Ca2+ in the infracted cortex and corpora striata begun to increase 2 h after the ischemia and was further enhanced with the prolongation of the ischemic time. No significance was found in the fluorescence intensity of Ca2+ between the cortex and corpora striata. The fluorescence intensity of Ca2+ in the infarcted corpora striata was obviously higher than that in the cortex after ischemia. Compared with that in the ischemic model group, the fluorescence intensity of Ca2+ in the infarcted cortex and corpora striata decreased significantly at 2 and 12 h following puerarin intervention (P<0.05). CONCLUSION: Puerarin treatment can relieve calcium overload, reduce cerebral ischemic volume and play a neuroprotective role against focal cerebral ischemia. Twelve hours following cerebral ischemic injury may be the time window for administering puerarin intervention. PMID- 20584656 TI - [Analysis of glucose levels and the risk for coronary heart disease in elderly patients in Guangzhou Haizhu district]. AB - OBJECTIVE: To investigate the prevalence of diabetes and prediabetes and their association with the risk for coronary heart disease (CHD) in elderly residents in Haizhu District of Guangzhou. METHODS: Stratified random sampling was employed to select a total of 1800 resident aged 50 years or older in the region. The fasting fingertip blood glucose>5.6 mmol/L was used as the criterion for the initial screening. The data were collected from qualified subjects via scheduled questionnaire surveys, blood collection and testing, and physical examination. The subjects were divided into the 3 groups, namely normal blood glucose, prediabetes, and diabetes groups. The combination rates of the relevant risk factors (hypertension, hyperlipemia, obesity, and central obesity) were compared among the groups by Framingham Heart Study to predict the occurrence of CHD in 10 years. RESULTS: The incidence was 11.00% for prediabetes and 7.56% for diabetes in the elderly residents in Haizhu District. The occurrence of hypertension, hyperlipemia, obesity, and central obesity was significant higher in the prediabetes and diabetes group than in the normal blood glucose group, and showed no significant differences between the former two groups. The 10-year risks for CHD were markedly higher in both the prediabetes and diabetes groups than in the normal blood glucose group, but similar between the former two groups. CONCLUSION: Elderly patients with prediabetes and diabetes have significantly increased 10-year risk for CHD in comparison with those with normal blood glucose, but the risk is similar between the former two groups, indicating a close association of IGR (impaired fasting glucose+ impaired fasting glucose) with CHD. Early control of blood glucose is essential to the prevention and control of CHD. PMID- 20584657 TI - [Three-dimensional design of surgery for mandibular retrusion]. AB - OBJECTIVE: To explore the feasibility of surgical design for mandibular retrusion using three-dimensional software. METHODS: Three-dimensional reconstruction was performed by Mimics software based on the preoperative CT data. The model of the maxillofacial region was imported into Rapidform software for measuring the associated parameters and Geomagic software for simulation of osteotomy. The reliability of the virtual operation was validated during the surgery. RESULTS: The model of mandibular retrusion was reconstructed and successfully used to simulate the surgery. The simulation result was applied in subsequent actual surgery and good surgical outcomes were achieved. CONCLUSION: The three dimensional software can be used to simulate the surgery for mandibular retrusion and improve the predictability and accuracy of the surgery. PMID- 20584658 TI - [Application of SELDI-TOF-MS in establishing a model for predicting radiotherapy response of hypopharyngeal cancers]. AB - OBJECTIVE: To detect the serum proteomic fingerprints in patients with hypopharyngeal squamous cell carcinoma (HPSCC) by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) protein chip array technique. METHODS: The serum samples were obtained from 58 HPSCC patients for protein expression analysis using SELDI-TOF Protein Chip technique and cation-exchange (CM10) protein array. All the spectra were compared and the qualified mass peaks with mass-to-charge ratios (m/z) between 1 and 70 kD were autotimatically detected. The tree analysis pattern was generated using Biomarker Patterns Software. RESULTS: The protein profiles of HPSCC serum were analyzed according to the clinical and pathological features of the patients and their treatment response. No significant difference was noted in the serum proteins between HPSCC patients with different statuses of cervical lympha node metastasis (P>0.05), and the difference between well differentiated and poorly differentiated HPSCC was only minor. No significant difference was found in the serum proteins between chemotherapy-sensitive patients and the insensitive patients (P>0.05), but 5 proteins were identified to be overexpressed in the sensitive patients (P < / = 0.05). Radiotherapy-sensitive HPSCC patients were segregated from the insensitive group with a sensitivity of 86.67% and specificity of 100%. CONCLUSION: The serum protein at the m/z value of 6115.74 is overexpressed in radiotherapy-sensitive HPSCC patients. Serum protein profiling allows the prediction of radiotherapy response in HPSCC patients, and the identified proteins may serve as candidate biomarkers for predicting the radiotherapy sensitivity of HPSCC. PMID- 20584659 TI - [Effect of ROUX-en-Y anastomosis and Billroth-II anastomosis after subtotal gastrectomy on blood glucose in type 2 diabetic patients]. AB - OBJECTIVE: To evaluate the effect of ROUX-en-Y anastomosis and Billroth-II anastomosis after subtotal gastrectomy on blood glucose in patients with type 2 diabetes. METHODS: From January 2006 to December 2009, 26 and 24 type 2 diabetic patients underwent subtotal gastrectomy for gastric cancer or gastric ulcer and received subsequent ROUX-en-Y anastomosis and Billroth-II anastomosis, respectively. Perioperative and postoperative blood glucose and glycosylated hemoglobin (HbA1c) were detected in these patients to identify the variations. RESULTS: In ROUX-en-Y group, the fasting blood glucose (FBG) of the patients decreased significantly in the first month after the operation (t=4.46, P<0.05), and the 2-hour postprandial glucose (2hPG) and HbA1c also underwent significant reductions in the first postoperative week and month, respectively (t=3.5, P<0.05; t=2.21, P<0.05). In Billroth-II group, the FBG decreased significantly till 6 months after the operation (t=2.0, P<0.05), and HbA1c reduction occurred 3 months after the operation (t=2.61, P<0.05). There were significant differences in FBG in the first postoperative month, 2hPG in the 6th month, and HbA1c in the 3rd month between the two groups (P<0.05). CONCLUSION: The ROUX-en-Y anastomosis and Billroth-II anastomosis after subtotal gastrectomy can both reduce blood glucose of type 2 diabetic patients, but the former approach has better effect. PMID- 20584660 TI - [Expressions of surviving, MMP2, TIMP1, CD44 and nm23 of two tumors originating from different immunosurveillance in the same patient]. AB - OBJECTIVE: To explore the differences in the survival, adhesion and diffusion capacity between different carcinomas originating from different immunosurveillance in the same patient. METHODS: The expressions of survivin, MMP2, TIMP1, CD44, and nm23 proteins were detected immunohistochemically in a patient with acute lymphoblastic leukemia and lymphoma after allogeneic blood stem cell transplantation. RESULTS: Survivin, MMP2, TIMP1, CD44, and nm23 proteins were positive in acute lymphoblastic leukemia samples obtained before transplantation and negative in the lymphoma tissue occurring after the transplantation. CONCLUSION: The expressions of survivin, MMP2, TIMP1, CD44, and nm23 proteins vary between the two carcinomas originating from different immunosurveillance in the same patient. PMID- 20584661 TI - [Effect of phosphatase PHLPP1 gene transfer on the proliferation of human umbilical vein endothelial cells]. AB - OBJECTIVE: To investigate the constituent expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in human umbilical vein endothelial cells (HUVECs) and the effect of PHLPP1 gene transfer on the proliferation of the cells in vitro. METHODS: Cultured HUVECs were transfected with pcDNA3-GFP or pcDNA3HA PHLPP1 via lipofectamine 2000. The cell proliferation ability was determined by cell counting and MTT colorimetric assay, and Western blotting was used to detect the protein expression of PHLPP1 in the cells. RESULTS: No PHLPP1 protein was detected in the non-transfected cells or pcDNA3-GFP-transfected cells. pcDNA3HA PHLPP1 gene transfection significantly increased PHLPP1 expression in the HUVECs (P<0.01), but the cell proliferation status remained unchanged (P>0.05). The absorbance of the cells measured by MTT assay was 0.134-/+0.0152, 0133-/+0.014 and 0.137-/+0.016, with cell counts of (8.293-/+0.962)x10(5), (7.937 /+0.101)x10(5) and (8.127-/+0.112)x10(5), respectively, showing no significant differences between the 3 groups (P>0.05). CONCLUSIONS: Phosphatase PHLPP1 may not be the most important signal protein in the regulation of HUVEC proliferation. PMID- 20584662 TI - [Mechanism of bortezomib in inducing apoptosis and improving chemosensitivity of Ishikawa cells]. AB - OBJECTIVE: To investigate the effect of bortezomib on the apoptosis and drug sensitivity of endometrial cancer cell line Ishikawa cells. METHODS: The IC50 of bortizomib, ADR, DDP and PTX in Ishikawa cells was determined using MTT method. After treatment with IC50 bortezomib for 6 and 12 h, the expressions of caspases 3, caspases-9 and bcl-2 genes were detected by RT-PCR, and the cell apoptotic rate and ROS level Ishikawa cells were evaluated by flow cytometry after treatment with half of the IC50 of the drugs for 24 h. RESULTS: The IC50 of bortizomib, ADR, DDP, and PTX was 71.6 nmol/L, 0.572 micromol/L, 67.4 micromol/L and 719.5 nmol/L, respectively. Bortizomib significantly increased the mRNA expressions of caspases-3 and caspases-9 but decreased the expression of bcl-2. Compared with the treatment with agents alone, combined treatment of the cells significantly improved the cytotoxicity of the chemotherapeutic agents (P<0.05) and increased the ROS level and the apoptosis of the cells. CONCLUSION: Bortizomib can inhibit the protein kinase to induce the apoptosis and enhance the chemosensitivity of Ishikawa cells. PMID- 20584663 TI - [PET and CT cross-modality medical image fusion based on out-location frame]. AB - OBJECTIVE: To develop a new method of PET and CT cross-modality medical image fusion based on out-location frame. METHODS: PET/CT cross-modality medical images were obtained based on the out-location frame and the external fiducial marker on the frame was used for rigid medical image registration. A variation model based on the wavelet transform was used for image fusion. RESULTS: The CT images were displayed by grey scale and overlaid with the PET images displayed by chromatic scale to obtain the image after registration and fusion. CONCLUSION: The method of external markers registration can be effective and accurate in achieving PET and CT image fusion. PMID- 20584664 TI - [Relationship between metabolic syndrome and general habits in daily life]. AB - OBJECTIVE: To study the relationship between life style and metabolic syndrome (MS). METHODS: Using identical protocol and questionnaire, 173 patients with MS and 173 without MS selected from the general population undergoing physical examinations in Guangdong General Hospital were surveyed for the risk factors of MS in their life style, and logistic regression analysis was performed to identify the risk factors. RESULTS: MS was significantly related to overweight, prolonged maintenance of sitting posture, and heavy life or work stresses, among which overweight was the most important factor contributing to MS (OR=11.442, P<0.000). Regular exercise, long exercise time, and anxiety were protective factors for MS. Meat intake, smoking, time of getting sleep and insomnia were not found to relate to MS. CONCLUSION: MS is correlated to some general habits in daily life, and a healthy life style may help in the prevention and treatment of MS. PMID- 20584665 TI - [Effects of continuous blood purification on hemodynamics and oxygenation in patients with acute respiratory distress syndrome]. AB - OBJECTIVE: To evaluate the effects of continuous blood purification on the hemodynamics and oxygenation in patients with acute respiratory distress syndrome (ARDS). METHODS: Twenty-one patients with ARDS were treated with continuous veno venous hemofiltration (CVVH) combined with plasma exchange. Hemodynamics and oxygenation were measured or calculated at scheduled intervals using Swan-Ganz catheters. RESULTS: The mean arterial pressure, partial pressure of arterial oxygen, oxygen delivery, oxygen consumption increased, heart rate, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, blood lactate concentration all decreased significantly after the treatment, and the oxygen extraction ratio underwent no obvious changes. CONCLUSIONS: Continuous blood purification can increase blood and oxygen supply but has no significant effects on oxygen extraction ratio in ARDS patients. PMID- 20584666 TI - [Ultrastructural change of the ectopic endometrium and its significance in endometriosis]. AB - OBJECTIVE: To analyze the ultrastructural characteristics of ectopic endometrium in endometriosis. METHODS: Ectopic endometria collected from patients with adenomyosis and ovarian endometriosis were examined under transmission electron microscope (TEM). RESULTS: In comparison to normal human endometrium, the ectopic glandular epithelium of adenomyosis patients showed reduced and shortened microvilli covering the surface of the secretory cells, with obviously increased, elongated and irregularly aligned cilia of ciliated cells projecting into the lumen. Numerous microvilli and cilia broke off from the cell surface and shed into the lumen. The mitochondria were enlarged, and multiple polyribosomes were present on the surface of RER. The Golgi apparatus with electron-lucent vacuoles was seen frequently. The glandular cells contained many lysosomes, lipofuscins and myelinosomes, and the cell nuclei showed varying shape and size. The nuclear membrane of the epithelial cells was irregularity. Cytoplasm protrusion containing a few organelles occurred and shed into the lumen. Some ectopic epithelial cells showed characteristic features of necrosis. The basement membrane became markedly tortuous and focal lysis of the extracellular matrix was seen. Ultrastructurally, the ectopic glandular epithelium in ovarian endometriosis showed short and sparse microvilli on the free surface of the secretory cells. Some microvilli broke off from the surface. The short cilia of the ciliated cells were seldom seen. The mitochondria were enlarged. The glandular cells contained small amounts of RER, many free ribosomes, Golgi apparatus, lipofuscins and myelinosomes. The nuclear membrane showed obvious irregularity. Some ectopic epithelial cells had giant nuclei. Cytoplasmic protrusions containing small amounts of organelles were observed in some ectopic epithelial cells. Apoptotic cell death occurred in some ectopic glandular epithelium cells. The basement membrane became markedly tortuous, and the decidual-like cells containing abundant short and club-shaped RER were observed. The number of macrophages was obviously increased. CONCLUSION: The ultrastructural change of the ectopic glandular epithelium in endometriosis promotes its transformation into endometriotic lesions. PMID- 20584667 TI - [Content analysis of total polyphenol in the leaves of Jatrophy curcas. L]. AB - OBJECTIVE: To establish a method for analyzing the content of total polyphenols in leaves of Jatropha curcas. L. METHODS: Gallic acid was used as reference substance, the content of total polyphenols was analyzed Folin-Ciocalteu chromatometry. RESULTS: There was a good linearity for gallic acid in the range of 0.002-0.010 g.L(-1). The content of total polyphenols in the leaves of Jatropha curcas. L was approximately 6.74% with RSD 0.75%. The sample solution was stable during 10-90 min with RSD 0.28%. The precision RSD was 0.23% and the average recovery 99.85% (n=5). CONCLUSION: This method is simple, fast and reproducible. PMID- 20584668 TI - [Postoperative analgesic effect of parecoxib sodium in patients with posterior spinal surgery]. AB - OBJECTIVE: To investigate the postoperative analgesic effect of parecoxib sodium in patients with posterior spinal surgery. METHODS: Eighty patients undergoing posterior spinal surgery under general anesthesia were randomly divided into parecoxib sodium group and placebo group (n=40). All the patients received a single dose of m ml morphine (1.0 mg/ml) as the background analgesia immediately after the operation. The patients in parecoxib sodium group were given 40 mg parecoxib sodium intravenously, and those in the placebo group received an equivalent volume of saline instead, and at 24 and 48 h after the operation, the same dose was repeated. The visual analog pain score, patient satisfaction and adverse reactions were recorded after the administrations. RESULTS: Compared with the placebo group, the patients in parecoxib sodium group had significantly lowered VAS score at 6, 12, 24, and 48 h after the operation (P<0.05). No significant differences were noted in the patient satisfaction and adverse reactions between the two groups. CONCLUSION: Postoperative short-term use of parecoxib sodium can can provide good postoperative analgesic effect in patients undergoing posterior spinal surgery. PMID- 20584669 TI - [Effect of Shengmaisan on learning and memory abilities and hippocampal nitric oxide synthase expression and neuronal apoptosis in rats with vascular dementia]. AB - OBJECTIVE: To observe the effect of Shengmaisan on the learning and memory abilities and the expression of nitric oxide synthase and neuron apoptosis in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of Shengmaisan for treatment of VD. METHODS: Wistar rats were divided randomly in to normal control group, sham-operated group, VD model group, high-dose Shengmaisan group, low-dose Shengmaisan group, and nimodipine group. In the latter 4 groups, bilateral common carotid artery occlusion (BCCAO) was performed to establish rat models of VD followed by intragastric administration of Shengmaisan at 10 or 30 g.kg(-1).day(-1) or nimodipine at 20 g.kg(-1).day(-1) accordingly. The rats in the control, sham-operated and model groups were given saline in the same manner. The improvement of learning and memory abilities of the rats was assessed using Morris water maze test, and NOS activity and neuronal apoptosis in the hippocampus were determined after the treatment. RESULTS: The learning and memory ability and hippocampal NOS activity and neuronal apoptosis in low-dose Shengmaisan group and nimodipine group were significantly different from those in the VD model group (P<0.01), but no significant differences were found between high-dose Shengmaisan group and nimodipine group (P>0.05). CONCLUSION: Shengmaisan can significantly improve the learning and memory abilities of VD rats but may not be able to totally reverse the damage. The therapeutic effect of Shengmaisan might be related to its effect in decreasing NOS activity and inhibiting neuronal apoptosis in the hippocampus. PMID- 20584670 TI - [Clinical significance of cathepsin B expressions in cervical cancer in tissues]. AB - OBJECTIVE: [corrected] To investigate cathepsin B (CB) expression in squamous cervical carcinoma and its relationship to the clinical and pathological condition. METHODS: CB expression was detected by immunohistochemistry in 56 cases of human invasive squamous cervical carcinoma (ISCC) tissues, 85 cases of cervical intraepithelial neoplasia (CIN) and 38 cases of normal cervical squamous epithelial tissue. The results were analyzed in relation to the grade of differentiation, depth of invasion and pelvic lymph node metastasis. RESULTS: The positive rates of CB were 87.5% (49/56), 48.3% (41/85) and 48.3% (41/85) in ISCC, CIN and normal tissue, respectively. CB expression in ISCC had significant differences from that ub the CIN and normal tissues (P<0.01). CB positive rates in the tissues with invasion of less than two thirds of the cervix and over two thirds of the cervix were 83.4% (28/34) and 95.5% (21/22) respectively, showing obvious differences between them (P<0.05). CB-positive rates also showed an obvious difference between the tissues with lymphatic metastasis and those without lymphatic metastasis [97.4% (37/38) vs 66.7% (12/18), P<0.05]. CB expression in ISCC was not related to the grade of differentiation. CONCLUSION: High expression of CB is closely associated with tumor infiltration and lymphatic metastasis of cervical cancer. PMID- 20584671 TI - [An analysis of the characteristics and etiology of hand, foot and mouth disease in a Guangzhou sentinel hospital from May to December, 2008]. AB - OBJECTIVE: To analyze the characteristics and etiology of hand, foot and mouth disease (HFMD) in a sentinel hospital of Guangzhou. METHODS: The epidemiological data and clinical specimens were collected from May to December, 2008 for virological investigations (viral isolation, RT-PCR and molecular identification) and phylogenetic analysis. RESULTS: A total of 309 clinical cases were reported, and the incidence was the highest in 2-4-year-old children, among whom only 15 developed complications, with human enterovirus 71 (HEV71) as the main pathogen (64.7%). Phylogenetic analysis indicated that ten Guangzhou EV71 isolates belonged to Cluster C4a. CONCLUSION: HFMD is an important infectious disease in children resulting from infections by HEV71 as the main pathogen in 2008, and the Guangzhou C4a strains co-evolved with the isolates from other provinces in China and the neighboring countries. PMID- 20584672 TI - [Effect of irbesartan on ACE2 expression in diabetic rat myocardium]. AB - OBJECTIVE: To explore the effect of irbesartan on angiotensin-converting enzyme 2 (ACE2) mRNA expression in diabetic rat myocardium. METHODS: Thirty 8-week-old male Wistar rats were randomly divided into control group (n=7), diabetic model group (n=14) and irbesartan group (n=9). Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), a blood glucose>16.7 mmol/L 72 h after the injection indicated successful establishment of diabetes. Four weeks after the modeling, the rats in irbesartan group were given 50 mg/kg irbesartan. ELISA was used to measure myocardial AngII content in the rats, and myocardial ACE2 mRNA expression was determined by real-time PCR. RESULTS: Myocardial AngII level in the diabetic model group was significantly higher than that in the control group (P<0.001). Irbesartan administration significantly lowered cardiac AngII levels in the diabetic rats (P<0.001). The rats in irbesartan group showed significantly increased myocardial ACE2 mRNA expression compared with those in the control and diabetic rat groups (P<0.05). CONCLUSION: Irbesartan can increase ACE2 mRNA expression in the myocardium, which might be one of the mechanisms underlying its effect in improving the cardiac function in diabetic rats. PMID- 20584673 TI - [Effect of small interfering RNA targeting Rac1 gene on colony formation of SW480 cells in vitro]. AB - OBJECTIVE: To construct a vector expressing small interfering RNA (siRNA) against Rac1 gene and observe its effect on soft agar colony formation of SW480 cells in vitro. METHODS: Oligos of 64 base pairs for hairpin RNA targeting Rac1 were chemically synthesized and annealed. The siRNA constructs for Rac1, produced by inserting the annealed oligos into the downstream of H1 promoter of linearized pSUPER, were confirmed by restriction digestion and DNA sequencing. The constructed Rac1-siRNA was transfected into SW480 cells and Western blotting was performed to assess the expression and interference efficiency of siRNAs against Rac1.The soft agar colony formation assay was used to study the effect of Rac1 gene silencing on SW480 cells. RESULTS: Restriction digestion and DNA sequencing showed that the siRNA targeting Rac1 gene was successfully constructed. The siRNA could effectively down-regulate the expression of Rac1 in SW480 cells. Soft agar colony formation assay showed that the colony number and diameter of SW480 cells was reduced after siRNA transfection. CONCLUSION: A vector expressing hairpin RNA against Rac1 gene are successfully produced, which significantly reduces the colony numbers and size of SW480 cells in vitro, suggesting that Rac1 plays an important role in the growth of colorectal cancer in vitro. PMID- 20584674 TI - [Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers]. AB - OBJECTIVE: To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. METHODS: From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. RESULTS: A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated to the survival of the patients. CONCLUSIONS: Zoledronic acid combined with chemotherapy is an effective treatment for NSCLC with bone metastases. Zoledronic acid is safe and well tolerated. Urinary NTX and serum BALP have a high value in the diagnosis, therapeutic effect monitoring and SRE prediction of NSCLC with bone metastases. PMID- 20584676 TI - [Therapeutic effect of tracheal anastomosis versus interventional bronchoscopy in the treatment of airway stenosis]. AB - OBJECTIVE: To compare the therapeutic effects of tracheal anastomosis and interventional bronchoscopy in the treatment of airway stenosis. METHODS: From February, 1990 to February 2008, 53 patients with airway stenosis including 32 male and 21 female patients aged 2 to 80 years (mean 38 years) received end-to end anastomosis or bronchoscopic stent-graft treatment in our hospital. End-to end anastomosis of the narrow sleeves resected was performed in 26 cases, balloon dilatation in 14 cases, and stent implantation in 13 cases. The clinical and follow-up data of the patients were analyzed retrospectively and the surgical outcomes were evaluated. RESULTS: No perioperative deaths occurred in these cases. Eight patients (5 with anastomosis, 2 with balloon dilation, and 1 with stent implantation) were lost to the follow-up ranging from 1 to 204 (mean 44.94 /+54.56) months. Of the patients available to the follow-up, 12 had airway restenosis, including 2 receiving end-to-end anastomosis (9.5%), 6 (50%) receiving balloon angioplasty, and 6 with granulation hyperplasia following stent implantation (50%). Of the 3 treatment, end-to-end anastomosis was associated with the lowest restenosis rate (Chi2=8.869, P=0.012). CONCLUSION: End-to-end anastomosis, with a low postoperative restenosis rate and better prognosis, should be the primary choice for treatment of tracheal airway stenosis. PMID- 20584675 TI - [Association of HLA-DR4, PAD4, and STAT4 expression in the peripheral blood with disease activity in patients with rheumatoid arthritis]. AB - OBJECTIVE: To explore the association of the expressions of human leukocyte antigen (HLA)-DR4, peptidyl arginine deiminase type4(PAD4), and signal transducer and activator of transcription 4 (STAT4) in the peripheral blood with the disease activity in patients with rheumatoid arthritis (RA). METHODS: Twenty-four RA patients in active stage (DAS28 score>or=2.6) and 14 RA patients in remission stage (DAS28 score<2.6) were enrolled in this study, with 12 healthy volunteers as the control. The QuantiGene Plex method was used to measure the expression level of HLA-DR4, PAD4, and STAT4 mRNA, and the relationship between the expressions of these genes and the DAS28 score, levels of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and rheumatoid factor (RF) was analyzed. RESULTS: The expressions of HLA-DR4, PAD4, and STAT4 were significantly higher in RA patients than in the healthy controls (P<0.05). The level of HLA-DR4 mRNA in the two RA groups showed no significant difference, but was significantly higher than that in the healthy controls. HLA-DR4 expression was not found to correlated to DAS28 score, anti-CCP antibody level or RF in the RA patients. The expressions of PAD4 and STAT4 were significantly different between the two RA groups (P<0.05). In the RA patients, PAD4 mRNA expression was positively correlated to DAS28 and anti-CCP antibody level (P<0.05), and STAT4 expression showed positive correlations to DAS28 and RF levels (P<0.05). CONCLUSION: HLA DR4, PAD4 and STAT4 are overexpressed in RA patients and may be involved in the pathogenesis of RA. The expressions of PAD4 and STAT4, but not HLA-DR4, are closely related to the disease activity of RA. Detection of peripheral blood PAD4 and STAT4 expressions can be helpful for evaluating the disease activity of RA. PMID- 20584677 TI - [Acupuncture at the acupoints of different meridians at the same anatomy level: a study with functional magnetic resonance imaging]. AB - OBJECTIVE: To investigate the response of the specific brain functional areas of normal human to acupuncture at the acupoints of different Meridians at the same anatomy level. METHODS: Twelve healthy young volunteers were enrolled in this research and functional magnetic resonance imaging (fMRI) scans were taken randomly in a block design. During the stimulation phase, an acupuncture needle inserted in right Shenmen (HT7) or Yanglao (SI6) was twirled at an angle of 180 degrees and a frequency of about 1.5 Hz. The collected images were analyzed using SPM2 for exploring the inter-group differences in blood oxygen level dependent (BOLD) responses. RESULTS Increases in BOLD signal (group analysis, corrected, 0.05, K>or=10) were found mainly in the right ostcentral gyrus of the frontal lobe (BA2, BA1, BA43) and left inferior frontal gyrus (BA47) by acupuncture at HT7, and chiefly in the left inferior parietal lobule (BA 40) and right inferior frontal gyrus (BA 45, BA 46) by acupuncture at SI6. CONCLUSION: Acupuncture of HT7 and SI6 elicits different BOLD responses in some related cerebral regions correlative with cognition. PMID- 20584678 TI - [Correlation between sleep apnea hypopnea syndrome and preeclampsia and the possible pathogenesis of preeclampsia]. AB - OBJECTIVE: To investigate the relationship between sleep apnea-hypopnea syndrome (SAHS) and preeclampsia and the possible pathogenesis of the latter. METHODS: Twenty-five healthy pregnant women, 43 pregnant women with preeclampsia, and 27 with preeclampsia complicated by SAHS were enrolled in this study. Apnea-hypopnea index (AHI) and the lowest arterial oxygen saturation (LSaO2) were measured through a 7-hour polysomnography (PSG), and the maternal age, gestational age, body mass index and 24-hour urine protein were recorded. RESULTS: All the indexes except for the maternal age and gestational age showed significant differences between the 3 groups. The two groups of preeclampsia patients showed a significant difference in BMI from the control cases. Significant positive correlations of AHI to BMI, MAP and 24-hour urine protein were noted; LSaO2 was found to inversely correlate to BMI, MAP, and 24-hour urine protein. In spite of the significant correlation of BMI to the other indexes, we found that BMI was less important than AHI and LSaO2. CONCLUSION: SAHS may induce or aggravate preeclampsia. Greater attention should be given to the presence of SAHS in pregnant women with obesity, but obesity is not the predominant predisposing factor for preeclampsia. PMID- 20584679 TI - [Effects of calponin-1 gene silencing on the biological behavior of uterine smooth muscle cells]. AB - OBJECTIVE: To study the effects of calponin-1 expression inhibition on the proliferation , invasiveness, apoptosis and cytoskeleton of uterine smooth muscle cells, and explore the molecular mechanism of calponin-1 in the uterine smooth muscle cells for labor onset. METHODS: siRNA-calponin-1 adenovirus plasmid was constructed and transfected into primarily cultured uterine smooth muscle cells. The proliferation, invasiveness and apoptosis of the cells were determined by MTT assay, matrigel invasion assays and flow cytometry, respectively. Rhodamine Phalloidin was used for labeling filamentous actin (F-actin), and the morphology and the distribution of F-actin was observed under fluorescence microscopy and analyzed quantitatively. RESULTS: The motor ability of uterine smooth muscle cells decreased significantly after transfection with siRNA-calponin-1 adenovirus plasmid (P<0.05). The transfected cells showed thinner, loosened and irregular F actin microfibers, and the cells in the empty vector and blank control groups showed thicker and longer F-actin microfibers. CONCLUSION: Inhibition of calponin 1 expression can inhibit uterine smooth muscle cell migration and cause the morphological change and rearrangement of F-actin without affecting its proliferation and apoptosis in vitro, suggesting that the morphological change and rearrangement of F-actin of uterine smooth muscle cell may be one of the important mechanisms in the labor onset. PMID- 20584680 TI - [Laparoscopic Roux-en-Y gastric bypass surgery for treatment of type 2 diabetes mellitus]. AB - OBJECTIVE: To investigate the surgical approach, feasibility and effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery for treating type 2 diabetes mellitus. METHODS: Seven obese patients with type 2 diabetes and 5 type 2 diabetic patients without obesity received LRYGB surgery. The changes of the body mass, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG), C peptide (C-P) and HbA1c% were observed postoperatively. RESULTS: LRYGB procedures were successfully performed in all the 12 patients with no conversion to open surgery. The resolution rate was 85.7% in the obese group and 80% in the non-obese diabetic group. CONCLUSION: LRYGB surgery is feasible for treatment of type 2 diabetes with good short-term result, but the long-term outcome awaits further observation. PMID- 20584681 TI - [PKC isoform selectivity and radiation-induced apoptosis of HepG2 cells]. AB - OBJECTIVE: To investigate the expressions of protein kinase C (PKC) isoforms in X ray-exposed HepG2 cells and identify the PKC isoforms that induce radioresistance in HepG2 cells. METHODS: Cultured HepG2 cells were divided into control group and 6 Gy radiation group for corresponding treatments. The fluorescence intensity (FI) and the percentage of positive cells were determined using flow cytometry. RESULTS: The FI of PKCalpha and PKCdelta were 2.28 and 5.05 in the radiation group, respectively, significantly higher than those in the control group (P<0.05). The percentages of PKCalpha- and PKCdelta -positive cells were significantly higher in the radiation group than in the control group (P<0.05). The FI and the percentages of PKC zeta, gamma, epsilon, zeta positive cells were rather low and showed no significant differences between the two groups (P>0.05); PKCbeta expression was not detected in the two groups of cells. The apoptosis rates of the control and radiation groups were 1.73% and 20.90%, respectively. CONCLUSION: PKCalpha and PKCdelta may be involved in protecting HepG2 cells from radiation-induced apoptosis. PMID- 20584682 TI - [Narcotrend index monitoring can predict the recovery of consciousness in patients undergoing abdominal surgery]. AB - OBJECTIVE: To investigate the value of Narcotrend (NT) index monitoring versus standard hemodynamic parameters in predicting the recovery of consciousness in patients undergoing abdominal surgery. METHODS: Forty ASA I or II patients undergoing elective abdominal surgery were randomized into two groups to receive sevoflurane-sufentanil anesthesia monitored by NT index or solely by clinical parameters. Anesthesia was induced with the inhalation of 8% sevoflurane and sufentanil target-controlled infusion at 0.2-0.5 ng/ml. The values of NT stage (NTS), NT index (NTI), and hemodynamic parameters (MAP and HR) were recorded during the period of recovery. The prediction probability (Pk) of each parameter was calculated and compared. RESULTS: NTS and NTl were closely correlated to the changes of consciousness during the recovery from general anesthesia. The Pk values of NTS and NTI in predicting eye opening and orientation recovery were 0.95, 0.92, and 0.92, 0.89, respectively, obviously higher than the Pk values of MAP and HR (P<0.05). CONCLUSION: NT monitoring can be used to effectively predict the recovery of consciousness in patients undergoing abdominal surgery and facilitates a significant reduction of the recovery time and sufentanil dosage during a sevoflurane-sufentanil anesthesia. PMID- 20584683 TI - [Tragus cartilage tympanoplasty for treatment of adhesive otitis media]. AB - OBJECTIVE: To evaluate the efficacy of cartilage tympanoplasty in the treatment of adhesive otitis media. METHODS: From June to October, 2008, 18 patients with adhesive otitis media (18 ears) were treated with tragus cartilage tympanoplasty. The air-bone gap changes and the self-perceived symptomatic improvement were evaluated at 1 month and 1 year after the operation. RESULTS: All the patients showed dry ear within 6 weeks after the operation. Tympanic membrane healing was achieved in 17 cases, and 1 case presented with a inferior-anterior fissure in the tympanic membrane. With the average preoperative air-bone gap (at 0.25, 0.5, 1.0, and 2.0 kHz) of 44.65 dB, the patients showed an obvious decrease of the air bone gap by over 10 dB at 1 month after the operation and by over 25 dB at one year. Symptomatic improvements were achieved in these cases, including alleviated ear discomforts (3/15 cases), total tinnitus relief (1/11 cases), and alleviated tinnitus (10/11 cases). High-frequency tinnitus was noted in 1 case (1/7 cases), and the tympanic membrane appeared normal in 17 cases. CONCLUSION: Tympanic membrane reconstruction using the tragus cartilage can be feasible for treatment of secretory otitis media, but the surgical indications should be carefully controlled. PMID- 20584684 TI - [Laparoendoscopic single-site surgery radical cystectomy with orthotopic taenia myectomy sigmoid neobladder: initial report]. AB - OBJECTIVE: To report the first case and detailed techniques of laparoendoscopic single-site surgery (LESS) radical cystectomy with orthotopic taenia myectomy sigmoid neobladder for organ-confined bladder cancer. METHODS: A 74-year-old man presented with gross hematuria for 2 months and biopsy revealed bladder cancer. LESS radical cystectomy and bilateral pelvic lymphadenectomies were performed using a single multilumen port inserted through a solitary 3.5 cm lower abdominal incision with conventional laparoscopic instruments. The taenia myectomy sigmoid pouch was then constructed by open procedure. RESULTS: The total operative time was 9.5 h, and the LESS procedure lasted for about 5.5 h. No other port incision was added. The final pathology revealed urothelial carcinoma. The estimated intraoperative blood loss was 600 ml with blood transfusion of 400 ml. The pelvic lymph nodes and the surgical margins of the ureters and urethra were all free of tumor invasion. No water electrolyte and metabolic acid-base balance disorders were observed perioperatively. The neobladder capacity was about 280 ml, with a residual urine volume of 10 ml and peak flow rate of 11.1 ml/s 3 months postoperatively. CONCLUSION: Although with a steep learning curve, LESS surgery can be a less invasive and promising alternative to muscle-invasive bladder carcinoma. PMID- 20584685 TI - [Expression of special AT-rich sequence-binding protein in bladder urothelial carcinoma and its clinical significance]. AB - OBJECTIVE: To detect the expression of special AT-rich sequence-binding protein (SATB1) in bladder urothelial carcinoma and investigate its correlation to the biological behavior of the carcinoma. METHODS: The expression of SATB1 mRNA was detected in 34 cases of bladder urothelial carcinoma and 14 normal bladder tissues by RT-PCR, and the protein expression of SATB1 was detected in 68 cases of bladder urothelial carcinoma and 17 normal bladder tissues by immunohistochemistry. The correlation between SATB1 expressions and the biological behavior of the tumor was analyzed. RESULTS: The expression of SATB1 was significantly higher in bladder urothelial carcinoma tissues than in normal bladder tissues (P<0.05). and the expression of SATB1 in the tumor tissues was correlated to the clinical stage and metastasis of the tumor. CONCLUSION: SATB1 expression can be associated with the development and metastasis of bladder urothelial carcinoma and may potentially serve as an indicator for predicting the prognosis of bladder urothelial carcinoma. PMID- 20584686 TI - [Correlation of multi-slice CT findings to clinical staging and prognosis of mesenteric blood vessel infarction]. AB - OBJECTIVE: To explore the correlation of multi-slice CT findings to the clinical staging and prognosis of intestinal obstruction due to mesenteric blood vessel infarction. METHODS: Fifty-four patients with intestinal obstruction resulting from infarction of the mesenteric vein or artery underwent multi-slice CT scanning, and the CT findings were analyzed for their relation with the intestinal ischemia and prognosis. RESULTS: Sixteen patients were confirmed to have mesenteric arterial thrombosis (29%) and 40 had mesenteric venous thromboses (71%) by multi-slice CT scanning. The total mortality rate was 29%, of which mesenteric artery infarction took up 87% and mesenteric vein infarction 5%. The prognosis of the patients was closely related to the cause of the bowel infarction. Such CT findings as increased intensity of the intestinal canal and decreased enhancement and thickening of the bowel wall indicated favorable prognosis, whereas the signs of paper-thin wall sign, fecal sign, pneumatosis of the bowel wall, mesenteric veno gas and pneumoperitoneum all suggested poor prognosis. CONCLUSION: Multi-slice CT scanning can identify mesenteric blood vessel infarction resulting in intestinal obstruction, and the CT signs can offer objective and valuable information for clinical staging and prognostic evaluation. PMID- 20584687 TI - [A retrospective analysis of the six-year data of peritoneal dialysis in a single center]. AB - OBJECTIVE: To investigate the epidemiology, peritoneal dialysis (PD) related complications and survival outcomes of 236 patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) in our center from January, 2004 to November, 2009. METHODS: The data including patient gender, age, time of PD initiation, addresses, types of medical reimbursement, primary diseases, modes of PD catheter placement surgery, types of PD catheter, PD related complications, and time of drop out were retrospectively analyzed. PD catheter migration rate, peritonitis rate, drop out rate (DOR), length of the time of PD therapy (TOT), and survival rate were calculated and compared with those of patients in other PD centers. RESULTS: The number of newly introduced patients increased gradually in the years from 2004 to 2009. The mean age of newly introduced patients was 47-/+16 years, and patients with age below 60 years accounted for 77.96%. Patients who paid for their own expenses accounted for 67.37% of all, and the rate of these patients decreased gradually. Similar to that in Asian-Pacific region, chronic glomerulonephritis was the most frequent cause of ESRD followed by diabetic nephropathy. The number of patients with chronic glomerulonephritis or obstructive nephropathy as the primary diseases was greater in this center than that reported in the Asian-Pacific region, accounting for 54.66% and 11.02% of all patients, respectively. In contrast, the patients with diabetic nephropathy or benign arteriolar renal sclerosis were less, accounting for 12.29% and 10.17% of all, respectively. PD catheter migration rate (8.05%) and peritonitis rate (1:44.22 patient-months) were both lower than those reported. The patient survival rates at 1, 2, 3 years were 83.65%, 51.59% and 29.81%, respectively, lower than those of other centers in the developed countries but higher than the mean levels in China. DOR decreased gradually to 11.56% in 2009, and TOT increased to 23.61 months. CONCLUSION: The above characteristics of the patients are related to many factors, including the "PD first" principle, high prevalence of urinary calculosis in the primary source regions of most patients, preventive partial omentum resection in some patients, education and follow-up for patients, and increased expense cover by medical insurance. PMID- 20584688 TI - [Expression of livin at the invasive tumor front of oral squamous cell carcinoma]. AB - OBJECTIVE: To study the expression of livin at the invasive tumor front of oral squamous cell carcinoma. METHODS: Forty-eight samples of oral squamous cell carcinoma were graded according to invasive front gading (IFG). The expression of livin was evaluated at the ITF and other parts of the same tumor using immunohistochemistry. RESULTS: Significant difference in the pathological grades was found between the ITF and the other parts of oral squamous cell carcinoma (P<0.01). The expression of livin at the ITF was significantly stronger than that in the other regions (P<0.01). A significant positive correlation was noted between livin expression and the TFG score (P<0.05). CONCLUSION: Inhibition of cell apoptosis is more obvious at the ITF of oral squamous cell carcinoma than in the other regions. Livin overexpression at the ITF may indicate greater malignancy and higher likeliness of tumor recurrence and metastasis. PMID- 20584689 TI - [Imaging features of primary pulmonary lymphoepithelioma-like carcinoma: report of 10 cases and literature review]. AB - OBJECTIVE: To study the imaging features of primary pulmonary lymphoepitheliom like carcinoma (LELC). METHODS: Ten cases of primary pulmonary LELC were confirmed by surgery and pathology. The findings in clinical pathology, X-ray and CT were retrospectively analyzed and the related references were reviewed. RESULTS: The clinical manifestations included coughing (5 cases), hemoptysis (2 cases), chest distress (4 cases), thoracodynia (3 cases), and fever (2 cases), with 3 cases being asymptomatic. Radiographically, primary pulmonary LELC appeared mainly as peripheral nodules or masses. The maximum diameter of the lesion was 2.3 to 12.4 cm. The lesions were slightly lobulated in 7 cases and spiky on the edge in 3 cases. Pleura retraction was shown in 3 cases. CT contrast scanning revealed light or significant enhancement in 5 cases. CONCLUSION: Primary pulmonary LELC has some characteristic imaging features, but X-ray and CT only are not sufficient for a definite diagnosis, which still relies on bronchoscopic biopsy and percutaneous pulmonary puncture biopsy. PMID- 20584690 TI - [Features of preoperative contrast-enhanced ultrasound of breast cancer: relationship with the syndrome classification in traditional Chinese medicine]. AB - OBJECTIVE: To analyze the relationship between the features of preoperative contrast-enhanced ultrasound and the differentiation of symptoms and signs for syndrome classification by traditional Chinese medicine (TCM). METHODS: Eighty two patients with malignant breast tumor were examined with contrast-enhanced ultrasound before the operation. The tumor diameter was greater than 2.0 cm in 48 cases and below 2.0 cm in 34 cases. According to the curative effect standard of TCM disorder, differentiation of symptoms and signs for classification of syndrome were performed, and the ultrasonic manifestations of different syndrome types were compared. RESULTS: In patients with maximum tumor diameter < or = 2 cm, Chong and Ren disorder type and liver Qi stagnation type were prevalent. In those with tumor diameter of <2 cm, Zeyi liver Qi stagnation type and virtual drug junction were more common. The mass peak intensity, slope of increase, enhancement intensity index and time-intensity curve of ultrasound differed significant between different syndrome types (P<0.05). CONCLUSION: The preoperative ultrasound features of breast cancer are associated with the syndrome types in TCM. PMID- 20584691 TI - [Effects of Liuweidihuang pills on pancreatic islet structure in OLETF rats]. AB - OBJECTIVE: To study the effects of Liuweidihuang pills on pancreatic islet structure in OLETF (Otsuka Long-Evans Tokushima Fatty) rats. METHODS: Forty male OLETF rats were divided randomly into Liuweidihuang pills group (Liuwei group) and control group (n=20). Ten male LETO rats were used as normal control group (LETO group). The rats in Liuwei group were given Liuweidihuang pills at the daily dose of 2.4 mg/kg intragastrically since the age of 8 weeks. Blood glucose was determined by OGTT. The rats were sacrificed at 8, 32 and 40 weeks and the pancreatic tissue was isolated to examine the morphological changes of the pancreas by HE staining and Masson trichrome staining. RESULTS: As the age of the rats increased, the pancreatic islets in the control group gradually showed fibrosis and islet atrophy, which were not found in Liuwei group. Masson staining visualized no fibrosis in Liuwei group. No significant pathological change occurred in the pancreatic islet of LETO rats. The rats in Liuwei group developed diabetes since 30 weeks of age and the incidence was 28.6% at 40 weeks, significantly lower than that in the control group (P<0.01). CONCLUSION: Liuweidihuang pills can prevent degeneration of the pancreatic islets in spontaneous OLETF rats. PMID- 20584692 TI - [Pure tone audiology for Meniere disease: a clinical analysis of 75 cases]. AB - OBJECTIVE: To analyze clinical pure tone test data in patients with Meniere disease and study the changes in the audiometic curve configuration. METHODS: A retrospective analysis was conducted of the pure tone test data in 75 cases (82 ears) from 1984 to 2008. The audiometic curve configuration was divided into 6 categories to analyze the relationship between the main curve types and the clinical stages. RESULTS The most common audiogram was the peak type (46.34%), followed by the falling type (19.51%) and the mountain type (12.19%), and the dip type was relatively rare (2.43%). No significant differences were found in the rate of peak audiograms between the clinical stages. The common audiogram peak frequency occurred at 2 kHz (47.39%). The top curve of 1-2 kHz had the largest proportion in mountain type audiograms (70%, 7/10 ears). CONCLUSION: The peak type and mountain type configuration are one of the audiological characteristics of Meniere disease, especially for 2 kHz peak, which may serve as the diagnostic features of Meniere disease in the vertigo patients on their first visit. PMID- 20584693 TI - [Correlation between ras gene and the resistance of nasopharyngeal carcinoma to cetuximab]. AB - OBJECTIVE: To explore the correlation of ras gene to the drug resistance of nasopharyngeal carcinoma to cetuximab. METHODS: Cultured 5-8F/Erbitux cells were induced by stepwise exposure to increasing doses of cetuximab. MTT assay was used to determine the IC50 (half inhibitory concentration) of cetuximab and the drug resistance index (RI). Western blotting was employed to detect the protein levels of H-ras and K-ras. Real-time PCR was used to detect the expression of H-ras and K-ras. Gene sequencing was performed to identify potential mutations in H-ras and K-ras genes. RESULTS: We successfully induced cetuximab-resistant 5-8F/Erbitux hNPC cells by stepwise exposure to increasing doses of cetuximab. After treatment with cetuximab for 3 and 5 days, the RI of 5-8F/Erbitux cells was 1.2 and 1.1, respectively. The 5-8F/Erbitux cells had increased levels of H-ras and K-ras protein expressions (P<0.001) and enhanced gene expressions of H-ras (P=0.016) and ras-p21 (P=0.113) with decreased K-ras gene expression (P=0.000). Sequence analysis identified no mutations in the H-ras and K-ras genes in codons 12, 13, 59, and 61. CONCLUSION: Gene amplification and overexpression of H-ras is the major mechanism that causes the drug resistance of 5-8F/Erbitux cells to cetuximab. PMID- 20584694 TI - [Value of carcinoembryonec antigen in biochemotherapy response monitoring in patients with Her-2-positive advanced breast cancer]. AB - OBJECTIVE: To assess the value of serum carcinoembryonec antigen (CEA) in monitoring the response to biochemotherapy by Herceptin plus taxol (TAX) in patients with Her-2-positive advanced breast cancer. METHODS: The changes in serum CEA level were investigated retrospectively after two cycles of biochemotherapy in 83 patients with Her-2-positive advanced breast cancer. The correlations between the changes and radiological objective response were analyzed. RESULTS: After two cycles of biochemotherapy, the clinical benefit rate (CBR) was 81.9%. In the 60 patients with lowered CEA level, the CBR was 85.0% (51/60), with a non-response rate of 15.0% (9/60); in contrast, the CBR was only 34.8% in 23 patients with elevated CEA, with a non-response rate of 65.2%, showing significant difference between the two groups (P<0.05). CONCLUSION: Serum CEA level can be used to monitor the therapeutic effect of biochemotherapy in patients with Her-2-positive advanced breast cancer. PMID- 20584695 TI - [Synergetic effect of self-prescribed decoction eliminating herpes in treatment of recurrent genital herpes]. AB - OBJECTIVE: To study the recurrence rate and clinical effect of the treatment of recurrent genital herpes with self-prescribed decoction eliminating herpes combined with recombinant human interleukin-2 (IL-2). METHODS: One hundred and forty patients diagnosed as having recurrent genital herpes were randomly divided into experimental group and control group, 10 each. The experimental group received treatment of self-prescribed decoction eliminating herpes combined with recombinant IL-2 and valaciclovir hydrochloride tablets, and the control group received recombinant IL-2 and valaciclovir hydrochloride tablets. RESULTS: The total effective rate and cure rate in experimental group were significantly higher than that in control group (P<0.01). There was a markedly lower recurrence rate of genital herpes in the experimental group (P<0.01). CONCLUSION: The self prescribed decoction eliminating herpes combined with recombinant human IL-2 is of quite effective against recurrent genital herpes and can significantly decrease the recurrence rate, thus further clinical study being necessary. PMID- 20584696 TI - [Risk factors for cerebral microbleeds]. AB - OBJECTIVE: To analyze the risk factors of cerebral microbleeds (CMBs). METHODS: A total of 113 patients with cerebrovascular diseases underwent examinations of magnetic resonance imaging (MRI) of the brain (including T1WI, T2WI, FLAIR, and SWI) and blood biochemical tests, and the brain regions, number and grades of the CMBs were analyzed. The association between CMBs and the cardiovascular risk factors were analyzed. RESULTS: A The occurrence and grade of CMBs were associated with the patients' age, hypertension, diabetes, lacunar infarction, diastolic blood pressure, systolic blood pressure and high-density lipoprotein (HDL) levels (P<0.05). CMB occurrence was significantly associated with diabetes, hypertension, and lacunar infarction (P<0.05), and its incidence varied significantly between different brain regions (P<0.05). CONCLUSION: Age, hypertension, diabetes, lacunar infarction, diastolic blood pressure, systolic blood pressure, and HDL are all risk factors for CMBs, among which diabetes, hypertension, and lacunar infarction are significant risk factors. CMBs occurs most frequently in the cortex and subcortical region, followed by the basal ganglia, thalamus, and the cerebellum, and most unlikely in the brainstem. PMID- 20584697 TI - [Effect of C5-siRNA silencing receptor C5 on myocardial ischemia injury in rats]. AB - OBJECTIVE: To study the effect of C5-siRNA on pathological changes after myocardial ischemia in rats. METHODS: Thirty healthy Sprague-Dawley rats were randomly divided into sham-operated group, ischemia group and C5-siRNA group. The cardiac ischemia models were established in ischemia group and C5-siRNA group by ligating the proximal end of the left anterior descending (LAD) coronary artery. The rats were infused with 100 microl/kg of C5-siRNA into myocardial tissue in C5 siRNA group and equal amount of normal saline in ischemia group and sham-operated group after ligating the LAD coronary artery for 30 min and then performed of ischemia for 4 hours. The cardiac index and left ventricular mass index were determined, morphological changes of myocardial tissue observed under optical microscope and the expression of C5 was detected by immunohistochemical staining and image analysis system. RESULTS: There were no statistically significant difference between the three groups in the left ventricular mass index and cardiac index in the rats after ischemia for 4 hours. Light microscopy indicated edema and degeneration of the myocardial tissue were milder in C5-siRNA group than in ischemia group, a small amount of red blood cells existed in the myocardial stroma of the former. The expression of C5 was increased more significantly in ischemia group and C5-siRNA group than in sham-operated group (P<0.001), but was decreased in C5-siRNA group more than in ischemia group with no statistically significant difference between the two groups (P=0.132). CONCLUSION: C5-siRNA could attenuate myocardial ischemia injury in rats by reducing inflammatory cell infiltration and expression of C5. PMID- 20584699 TI - Healthcare workers' self-reported effect of an interventional programme on knowledge and behaviour related to infection control. AB - INTRODUCTION: Adherence to infection control guidelines is low, and several efforts have been made to improve healthcare workers' performance of infection control measures. In this study, the performance and evaluation of a hospital wide infection control programme is described. The most important measure was distribution of an infection control newsletter. METHODS: In evaluation of the programme, a randomised selection of healthcare workers received a questionnaire to investigate in what degree the healthcare workers was aware of the programme and whether they reported behavioural change and refreshed knowledge as result of the programme. RESULTS: The intervention made it possible to reach >80% of the personnel in a Norwegian university hospital. Among those who actually read Infection Control Newsletter, 92.9% reported that their knowledge was refreshed and 60.6% reported behavioural change. DISCUSSION: The intervention had a significant impact on nurses and nurse assistants' reports on knowledge and behaviour related to infection control. Our study supports the importance of a long-term and multimodal approach to healthcare workers in infection control work. The time and resources spent to produce and distribute the Infection Control Newsletter was an effective way to reach out to a large number of healthcare workers. PMID- 20584698 TI - Preventing the obesity epidemic by second generation tailored health communication: an interdisciplinary review. AB - BACKGROUND: The prevention of obesity and health concerns related to obesity are major challenges worldwide. The use of eHealth communication and the tailoring of information delivered via the Internet at the individual level may increase the effectiveness of interventions. Mastering behaviors related to nutrition, physical activity, and weight management are the main issues in preventing obesity, and the need for interdisciplinary knowledge within this area is obvious. OBJECTIVE: The objectives were to review the literature on tailored health communication and to present an interdisciplinary analysis of studies on "second" generation tailored interventions aimed at behavior change in nutrition, physical activity, or weight management. METHODS: A literature search was conducted of the main electronic information sources on health communication. Selection criteria were defined, and 23 intervention studies were selected. The content analysis focused on the following: study designs, objectives of behavior change, target groups, sample sizes, study lengths, attrition rates, theories applied, intervention designs, computer-based channels used, statistically significant outcomes from the perspective of tailoring, and possible biases of the studies. However, this was not a structured meta-analysis and cannot be replicated as such. RESULTS: Of the 23 studies, 21 were randomized controlled trials, and all focused on behavior change: 10 studies focused on behavior change in nutrition, 7 on physical activity, 2 on nutrition and physical activity, and 4 on weight management. The target groups and the number of participants varied: 8 studies included more than 500 participants, and 6 studies included less than 100. Most studies were short; the duration of 20 studies was 6 months or less. The Transtheoretical Model was applied in 14 of the 23 studies, and feedback as a tailoring mechanism was used in addition to an Internet site (or program) in 15 studies and in addition to email in 11 studies. Self-reporting was used in 15 studies, and 14 studies did not have a no-information control group. Tailoring was more effective in nutrition interventions than in physical activity and weight management interventions. The outcomes were mixed or negative in 4 studies of physical activity interventions and in 3 studies of weight management. The use of a no-information control group seemed to have been linked to statistically significant between-group effects in measuring physical activity. This bias effect related to intervention design may explain the differences in the outcomes of the physical activity studies. CONCLUSIONS: Tailoring was shown to have been an effective method in nutrition interventions, but the results for physical activity were mixed, which is in line with previous studies. Nevertheless, the effect of possible biases, such as relying solely on self-reports and on intervention design without a no-information control group, should not be underestimated. Thus, the issue of bias merits more attention in planning interventions and in future meta-analyses. PMID- 20584700 TI - Patient safety begins with proper planning: a quantitative method to improve hospital design. AB - BACKGROUND: A quantitative methodology that enhances design of patient-safe healthcare facilities is presented. The prevailing paradigm of evaluating the design of healthcare facilities relies mainly on postconstruction criticism of design flaws; by then, design flaws may have already negatively affected patient safety. The methodology presented here utilises simulation-based testing in real size replicas of proposed hospital designs. Other simulations to assess design solutions generated mainly qualitative data about user experience. To assess the methodology, we evaluated one patient safety variable in a proposed hospital patient room. METHOD: Fifty-two physicians who volunteered to participate were randomly assigned to examine a standardised patient in two hospital room settings using a replica of the proposed architectural plan; the two settings differed only by the placement of the alcohol-based hand-rub dispenser. The primary outcome was the hand hygiene compliance rate. RESULTS: When the dispenser was in clear view of the physicians as they observed the patient, 53.8% sanitised their hands. When the dispenser was not in their field of view (as in the original architectural plan), 11.5% sanitised their hands (p=0.0011). Based on these results, the final architectural plans were adjusted accordingly. CONCLUSION: The methodology is an effective and relatively inexpensive means to quantitatively evaluate proposed solutions, which can then be implemented to build patient-safe healthcare facilities. It enables actual users to proactively identify patient safety hazards before construction begins. PMID- 20584701 TI - 'Quod scripsi, scripsi.' The quality of the report of telephone consultations at Dutch out-of-hours centres. AB - OBJECTIVE: To assess the quality of the content of reports of telephone consultations at out-of-hours centres and to investigate to what extent the reports reflect the actual telephone consultation. DESIGN AND SETTING: Cross sectional qualitative study; 17 out-of-hours centres in The Netherlands. METHOD: To assess the quality of the content of reports, a focus group developed the Reason for calling, Information gathered, Care advice given, Evaluation of the care advice with the patient (RICE) report rating instrument. Telephone Incognito Standardised Patients presented seven different clinical problems three times to 17 out-of-hours centres. All calls were recorded and transcribed. The out-of hours centres being called were asked for a copy of the report of the call. The authors assessed the quality of the content of the reports and compared this with the transcripts. RESULTS: The out-of-hours centres returned a report for 78% of the 357 calls. For the remaining 22% of the calls, no report was written. Reports contained almost always information about the medical reason for calling but little information about details of the clinical history. Patients' expectation, personal situation or perception of the care advice was seldom documented. In all but one out-of-hours centre, answers to obligatory questions were reported by triagists, although they had not been asked, varying between 1% and 54% of all questions entered. Triagists entered a subjective evaluation of a patients' condition in 12% of the reports. CONCLUSION: Reports of telephone consultations of out-of-hours centres contained little information on patients' clinical and personal condition. This could potentially endanger patients' continuity of care and might pose legal consequences for the triagist. PMID- 20584702 TI - Comparison of methods for identifying patients at risk of medication-related harm. AB - BACKGROUND: With the introduction of Computerised Physician Order Entry (CPOE) in routine hospital care, a great deal of effort has been put into refining Clinical Decision Support Systems (CDSS) to identify patients at risk of preventable medication-related harm. OBJECTIVES: This study compared a CPOE with basic CDSS and 16 clinical rules with a manual pharmacist medication review to detect overdose and drug-drug interactions that actually required a change in medication. METHODS: The study involved the review of 313 patients admitted over 5 months at an internal medicine ward where a change in medication as a result of dosing of therapeutic errors was detected by a manual medication review by a trained pharmacist. Subsequently, all these patients' medication orders (MOs) were entered into the authors' CPOE with basic CDSS. Medication orders with a safety alert indicating overdose and drug-drug interactions generated by the authors' CPOE with basic CDSS were compared with the same type of medication errors identified through manual review. The positive predictive value (PPV), sensitivity and specificity compared with manual review were determined. Second, a set of 16 clinical rules was applied to the patient and prescribing data. The overlap between the clinical rules and manual review was determined by comparing patients triggered by the clinical rule with patients with a corresponding error in the manual medication review. RESULTS: Manual medication review identified 57 medication errors involving overdose and 143 therapeutic errors of which 46 were drug-drug interactions. The CPOE with basic CDDS generated 297 safety alerts involving overdose (PPV 0.06, sensitivity 0.32, specificity 0.92) and 365 safety alerts involving drug-drug interactions (PPV 0.12, sensitivity 0.96, specificity 0.91). The clinical rules generated 313 safety alerts identifying 39% of all the overdoses and therapeutic errors found in the manual review at which they were targeted. In 23% of the alerts generated by a clinical rule, the patients actually required a change of medication as indicated by the manual review. When CPOE with basic CDSS and the rules were combined, 66% of the overdoses and therapeutic errors were identified. CONCLUSIONS: The authors' CPOE with basic CDSS and the clinical rules are useful early strategies for preventing medication related harm. They could be a first step towards more advanced decision support. These computerised systems will be even more useful in daily practice, once they are further fine-tuned to decrease the number of alerts that need no clinical action. PMID- 20584703 TI - Application of the ICF to referral delay in total joint arthroplasty. AB - BACKGROUND: The factors that affect referral for total joint arthroplasty (TJA) have been widely studied. Implicit in this work is the assumption that patient health status should determine priority for surgery. However, specification of patient health status lacks a strong theoretical framework. This study employs the WHO model of health outcomes, the International Classification of Functioning, Disability and Health (ICF), to examine patient health factors in the referral process for TJA. METHODS: Within 8 weeks prior to TJA, 260 patients electing for primary TJA completed a questionnaire which measured the ICF (impairment, activity limitations and participation restrictions) and four types of delay in their journey from initial consultation with their primary care physician to surgery. RESULTS: Impairment did not affect any stage of the referral process. In contrast, patients who had experienced a delay of 26 weeks or less between referral to a surgeon and being placed on the waiting list for surgery reported greater activity limitations and participation restrictions than patients who had waited more than 26 weeks. Further, patients who reported having wanted surgery for more than 52 weeks reported greater participation restrictions than patients who had wanted surgery for less than 52 weeks. CONCLUSIONS: The ICF identifies three health outcomes, two of which (activity limitations and participation restrictions) are related to delay in the referral process for TJA. The ICF is a useful theoretical framework for the study of factors that influence prioritisation for surgery. The level of functional and social disability appears to inform prioritisation for TJA by consultant orthopaedic surgeons. PMID- 20584704 TI - Overcoming barriers to guideline implementation: the case of cardiac rehabilitation. AB - AIMS: This study explored the strategies used by cardiac rehabilitation (CR) coordinators to overcome the obstacles to implementation of the evidence-based Reducing Risk in Heart Disease guidelines. METHODS: The study design used qualitative, semistructured in-depth interviews with 20 CR coordinators from New South Wales, Australia, to explore the strategies used to facilitate guideline implementation. Non-probability sampling was used to recruit CR coordinators to obtain a broad understanding of the issues. Interviews were transcribed and thematic content analysis was undertaken to identify common themes. RESULTS: Coordinators addressed the barriers to implementing guidelines through their commitment to best practice and striving to overcome the odds through providing opportunistic health education, alternate methods of secondary prevention, and partnering and engaging with local communities. CONCLUSIONS: Although CR coordinators face multiple barriers to implementing evidence-based guidelines for patients with coronary heart disease, they use strategies such as harnessing community capacity and using available resources creatively. The development of a more integrated, multifactorial and coordinated approach to improving use of guidelines in clinical practice to improve the treatment and secondary prevention of coronary heart disease is urgently needed. PMID- 20584705 TI - The relationship between external and local governance systems: the case of health care associated infections and medication errors in one NHS trust. AB - BACKGROUND: 'Organisational governance'--the systems, processes, behaviours and cultures by which an organisation leads and controls its functions to achieve its objectives--is seen as an important influence on patient safety. The features of 'good' governance remain to be established, partly because the relationship between governance and safety requires more investigation. AIMS: To describe external governance systems--for example, national targets and regulatory bodies- and an NHS Trust's formal governance systems for Health Care Associated Infections (HCAIs) and medication errors; to consider the relationships between these systems. METHODS: External governance systems and formal internal governance systems for both medication errors and HCAIs were analysed based on documentary analysis and interviews with relevant hospital staff. RESULTS: Nationally, HCAIs appeared to be a higher priority than medication errors, reflected in national targets and the focus of regulatory bodies. Locally, HCAIs were found to be the focus of committees at all levels of the organisation and, unlike medication errors, a central component of the Trust's performance management system; medication errors were discussed in appropriate governance committees, but most governance of medication errors took place at divisional or ward level. DISCUSSION: The data suggest a relationship between national and local prioritisation of the safety issues examined: national targets on HCAIs influence the behaviour of regulators and professional organisations; and these, in turn, have a significant impact on Trust activity. A contributory factor might be that HCAIs are more amenable to measurement than medication errors, meaning HCAIs lend themselves better to target-setting. PMID- 20584706 TI - Reducing referral delays in colorectal cancer diagnosis: is it about how you ask? AB - OBJECTIVES: Delays in colorectal cancer (CRC) diagnosis related to colonoscopy referrals are not well studied. The authors tested whether certain details of information transmitted through computerised provider order entry (CPOE)-based referrals affected timeliness of diagnostic colonoscopy for patients with newly diagnosed CRC. METHODS: The authors studied a 6-year cohort of all newly diagnosed patients with CRC at a large tertiary care Veterans Affairs hospital and its affiliated multispecialty clinics. Referring providers included primary care clinicians, resident trainees and other specialists. From the colonoscopy referral preceding CRC diagnosis, the authors determined request date, type and frequency of diagnostic clues provided (symptoms, signs, test results), notation of urgency, and documented evidence of verbal contact between referring provider and consultant to expedite referral. The authors compared distributions of proportions of diagnostic clues between patients with a lag of >60 and <=60 day, and examined predictors of lag time. RESULTS: Of 367 electronic referrals identified with a median lag of 57 days, 178 (48.5%) had a lag of >60 days. Referrals associated with longer lag times included those with 'positive faecal occult blood test' (92 days, p<0.0001), 'haematochesia' (75 days, p=0.02), 'history of polyps' (221 days, p=0.0006) and when 'screening' (vs specific symptoms) was given as the reason for diagnostic colonoscopy (203 days, p=0.002). Independent predictors of shorter wait times included three diagnostic clues, notation of urgency and documentation of verbal contact. CONCLUSIONS: Attention to certain details of diagnostic information provided to consultants through CPOE based referrals may help reduce delays in CRC diagnosis. PMID- 20584707 TI - Giant cell arteritis in Asians: a comparative study. AB - BACKGROUND: Giant cell arteritis (GCA) is a common systemic vasculitis, with a presumed Caucasian predominance. The occurrence of GCA in Asians has rarely been addressed. This study aims to assess the incidence of giant cell arteritis in Asians. METHODS: In this retrospective review, the self-reported ethnicities of patients with biopsy-proven GCA at the University of California-San Francisco (UCSF) were recorded. Ethnic distribution of the patient population served by UCSF was estimated from an age- and sex-matched control group. The odds ratio for each ethnicity (Asian and Caucasian) was determined and compared using Fisher's exact test and logistic regression analysis. RESULTS: The ethnic distribution of the 38 patients with positive temporal artery biopsies were as follows: Caucasian n=31 (81.6%), Asian n=1 (2.6%) and other n=6 (15.8%). The ethnic distribution of the patient population served by UCSF was as follows: Caucasian 42%, Asian 28% and other 30%. The difference in the proportion of GCA in Asians and Caucasians was statistically significant (OR 0.049 (95% CI 0.0065 to 0.374), p=0.0036). CONCLUSIONS: In our patient population, GCA was seen 20 times less frequently in Asian than Caucasian patients. Although this difference is significantly different (p=0.036), given the small sample size and wide CI this should be viewed as a rough estimate. PMID- 20584708 TI - Comparison of corneal changes after phacoemulsification using BSS Plus versus Lactated Ringer's irrigating solution: a prospective randomised trial. AB - BACKGROUND/AIMS: To compare two intraocular irrigating solutions, Balanced Salt Solution Plus (BSS Plus) versus Lactated Ringer's (Ringer), for the preservation of corneal integrity after phacoemulsification. METHODS: 110 patients undergoing phacoemulsification were randomised to either BSS Plus (n=55) or Ringer (n=55) as the irrigating solution. Patients were examined at baseline and at 1, 8, 15, 30 and 60 days postoperatively. Evaluations included specular microscopy to evaluate endothelial cell density (ECD) and endothelial cell size variability (CV), and corneal pachymetry for central corneal thickness (CCT) measurement. RESULTS: Groups were well balanced regarding baseline ECD, CV and CCT (p>0.05). There was no statistically significant difference between ECD reduction in group BSS Plus 13.1 +/- 2.0% and Ringer 9.2 +/- 1.9% (p<0.05) at day 60 or in any study visit. There was no statistically significant difference between CV increase in group BSS Plus 23.0 +/- 3.0% and Ringer 20.2 +/- 4.0% (p<0.05) at day 60 or in any study visit. CCT was significantly increased (p<0.05) at 1, 8, 15 and 30 days postoperatively, returning to baseline at 60 days in both groups. There was no significant difference in CCT increase in both groups at any visit. Interestingly, there were statistically significant correlations between ECD loss and phacoemulsification time (p<0.0001) and ECD loss and irrigation solution volume (p<0.0001) in the Ringer group, but not in the BSS Plus group. CONCLUSIONS: Ringers solution was similar to BSS Plus for corneal preservation in atraumatic cataract surgery. However, our study demonstrates that there is a trend towards lower postoperative endothelial cell density for surgeries with longer phacoemulsification time and higher irrigation volumes if Ringer is used. Trial registration number NCT00801358. PMID- 20584709 TI - Sequential versus concurrent KERARINGS insertion and corneal collagen cross linking for keratoconus. AB - PURPOSE: To evaluate the safety and efficacy of combined intracorneal ring segments (KERARINGS) insertion and corneal collagen cross-linking (CXL) performed in one session or two sessions and to present the refractive outcomes. SETTING: Magrabi Eye Hospital, Cairo, Egypt. METHODS: This prospective comparative study included 16 eyes of 10 patients with progressive mild to moderate keratoconus that were randomly divided into two groups. Group 1 included nine eyes that underwent KERARINGS insertion followed by CXL 6 montsh later; group 2 included seven eyes that underwent the two procedures at the same day. In both groups channel creation was performed using the femtosecond laser (Intralase FS 60). RESULTS: There was statistically significant improvement in both groups' uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), with significant reduction in refractive error and keratometric values (p<0.05). There was no statistically significant difference between both groups regarding the changes in UDVA, CDVA and refractive error (p>0.05). However, group 2 revealed more statistically significant reduction of keratometric values on topographical examination (p=0.046). The stromal haze that developed in both groups was more marked and persistent in group 2 than in group 1. CONCLUSION: Combined KERARINGS insertion and CXL can be performed safely in one or two sessions. However, the same-session procedure appears to be more effective regarding the improvement in the corneal shape. PMID- 20584710 TI - Vitreoschisis in macular diseases. AB - OBJECTIVES: Vitreoschisis is a possible pathogenic mechanism in macular diseases. Thus, the vitreoretinal interface was evaluated in monkey eyes and patients with various macular diseases in search of vitreoschisis. It is hypothesised that vitreoschisis is present in macular holes (MH) and macular pucker (MP), but not in other maculopathies. METHODS: Histopathology was studied in 14 monkey eyes and a vitrectomy specimen of a patient with macular pucker. Optical coherence tomography/scanning laser ophthalmoscopy (OCT/SLO) was performed in 239 eyes: 45 MH, 45 MP, 51 dry age-related macular degeneration (AMD), 53 non-proliferative diabetic retinopathy (NPDR) and 45 controls. RESULTS: Immunohistochemistry demonstrated lamellae in the posterior vitreous cortex of 12/14 (86%) monkey eyes. With OCT/SLO, vitreoschisis was detected in 24/45 (53%) MH and 19/45 (42%) MP eyes, but in only 7/53 (13%) NPDR, 3/51 (6%) AMD and 3/45 (7%) control eyes (p<0.001 for all comparisons). Rejoining of the inner and outer walls of the split posterior vitreous cortex was visible in 16/45 (36%) MH eyes and 15/45 (33%) MP eyes. Histopathology of the MP specimen confirmed a split with rejoining in the posterior vitreous cortex. CONCLUSIONS: Vitreoschisis was detected in half of eyes with MH and MP, but much less frequently in controls, AMD and NPDR patients. These findings suggest that anomalous PVD with vitreoschisis may be pathogenic in MH and MP. PMID- 20584711 TI - Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis. AB - AIM: To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. RESULTS: At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by >= 50% (n=12) or topical steroids reduced to <= 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate. PMID- 20584712 TI - Course of pattern-reversed visual evoked cortical potentials in 30 eyes after bony orbital decompression in dysthyroid optic neuropathy. AB - AIM: To investigate optic nerve function using the pattern-reversed visual evoked cortical potentials (VECP) before and after bony orbital decompression in dysthyroid optic neuropathy (DON) due to Graves' disease. METHODS: A total of 30 eyes of 15 patients (n=14 female) were observed over 30 +/- 13 months after bony three-wall orbital decompression. We examined visual acuity (VA), VECP P100 amplitudes and latencies, as well as proptosis using Hertel's exophthalmometry. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) VA increased, statistically significantly, by 2.4 lines during 30 +/- 13 months (from 0.38 +/- 0.25 before surgery to 0.14 +/- 0.1 at the end of observation, p=0.0001). All eyes maintained or improved vision by at least one line. Mean postoperative reduction of proptosis was 6.4 +/- 3 mm. While VECP P100 amplitudes improved significantly, P100 latencies remained abnormal in 18 eyes (60%) during follow-up of 10 +/- 7 months. Nine eyes (30%) with previous latency defects improved in at least one check test, five of which normalised completely. Worsening was evident in seven eyes (23%), and three previously normal eyes developed new pathological latencies. P100 latencies in 14 eyes (47%) remained unchanged. CONCLUSION: After decompression surgery, DON remission was observed in all patients regarding vision and VECP amplitudes. New or persistent P100 latency defects were seen in 60% of eyes after surgery. DON is considered to be caused by compressive ischaemic damage, which further underlines the importance of early decompression surgery. PMID- 20584713 TI - The effect of myopia on retinal nerve fibre layer measurement: a comparative study of spectral-domain optical coherence tomography and scanning laser polarimetry. AB - BACKGROUND/AIM: To evaluate the effect of myopia on retinal nerve fibre layer (RNFL) thickness measurement by using spectral domain optical coherence tomography (Cirrus HD OCT) and scanning laser polarimetry with enhanced corneal compensator (GDx ECC). METHODS: One hundred and forty-nine eyes of 149 myopic subjects were recruited and subdivided into three groups according to their refractive errors: high myopia group (spherical equivalent (SE) <= -6 D); moderate group (-3 D >= SE > -6 D); low group (-0.5D >= SE > - 3 D). RNFL thickness was measured by Cirrus High Definition (HD) OCT and GDx ECC. Associations between RNFL thickness and axial length/SE were evaluated by using Pearson correlation analysis. RESULTS: Average RNFL thickness measured with Cirrus OCT correlated significantly with axial length (r = -0.322, p < 0.001) and SE (r = 0.291, p < 0.001). No significant correlation was detected between axial length (r = -0.068, p = 0.407)/SE (r = 0.109, p = 0.187) and RNFL thickness measured with GDx ECC. CONCLUSION: Average RNFL thickness measured with Cirrus HD OCT decreases as the degree of myopia increases while no such correlation was detected in GDx ECC. Histological studies are warranted to further our understanding of the relationship between RNFL thickness and myopia. PMID- 20584714 TI - Ex vivo confocal microscopy of human corneal nerves. AB - AIMS: To evaluate the distribution, morphometry and the postmortem changes of the central and peripheral human corneal nerves by exvivo laser-scanning confocal microscopy (EVCM). METHODS: 24 eyes from 14 cadavers were retrieved at different time intervals after death and examined by EVCM. Five regions were examined in each eye: central, superior, inferior, temporal and nasal. In each region, corneal nerve images were categorised according to their anatomical location in the cornea into sub-basal, stromal and limbal nerves. Five nerve parameters were measured: density, orientation, diameter, numbers and branching pattern. RESULTS: Exvivo confocal scanning of a motionless eye allows high quality imaging and tracking of corneal and limbal nerves. Stromal nerves from the sub-Bowman's plexus perforate the Bowman's zone and terminate in bulb-like structures, from each of which a leash of sub-basal nerves arises. Following death, sub-basal nerve parameters showed significant changes. The density decreased from 9.23+/ 4.48 to 0.45+/-0.07 mm/mm(2), the diameter from 4.01+/-0.81 to 2.08+/-0.20 microm, the numbers from 8.3 to 1.0 and branching pattern from 39.38% to 0% (p<0.05) from day 1 to day 5 postmortem. Stromal and limbal nerves showed no significant changes in their density and diameter. CONCLUSIONS: This study establishes a direct link between sub-basal nerves and the sub-Bowman's nerves via distinct terminal bulbs. Limbal nerves are the thickest, are seen in all quadrants and can be traced to the corneal centre. The sub-basal nerve plexus rapidly degenerates after death but stromal and limbal nerves survive during the first five days after death. PMID- 20584715 TI - Retinopathy of prematurity: keeping the status quo. A case series detailing the importance of keeping the current guidelines for screening. PMID- 20584716 TI - Relationship between serum infliximab levels and acute uveitis attacks in patients with Behcet disease. AB - AIM: To investigate the relationship between the serum concentration of infliximab, a chimeric monoclonal antibody to tumour necrosis factor-alpha (TNF alpha), and its effectiveness in treating uveitis in Behcet disease. METHODS: The authors studied 20 patients with Behcet disease who had been treated with infliximab (5 mg/kg). After informed consent was obtained, samples of the peripheral blood were taken. The authors began collecting blood samples after at least 4 months of infliximab infusions. The first sample was collected at 1 h after an infliximab infusion (Day 0), then after 4 weeks (Week 4), and finally at 1 h prior to the infliximab infusion 8 weeks later (Week 8). The clinical data on uveitis were collected from the clinical charts of the patients. The serum concentration of infliximab was measured by an enzyme-linked immunosorbent assay. RESULTS: The mean serum concentration of infliximab in the 20 patients was 117.4 +/- 28.2 MUg/ml on Day 0, 11.4 +/- 6.8 MUg/ml on Week 4 and 6.3 +/- 4.8 MUg/ml on Week 8. The serum concentration of infliximab in each patient was significantly correlated with its effectiveness in resolving the recurrent episodes of uveitis. CONCLUSION: Monitoring infliximab serum concentrations is useful in determining the effectiveness of infliximab treatments for uveitis in Behcet disease. PMID- 20584717 TI - Epistaxis or epiphora as a sign for extension of a conjunctival melanoma. A series of six patients with nasolacrimal recurrence. AB - PURPOSE: To characterise malignant conjunctival melanomas with extension and recurrence in the nasolacrimal system. METHODS: Localisation of the primary tumour and recurrences of 210 conjunctival melanomas treated in The Netherlands were reviewed for orbital and nasal tumours (1978-2008). Based of these cases and literature data, characteristics for nasolacrimal system extension and metastasis were reviewed. RESULTS: Six patients (3%) showed a recurrence of the primary conjunctival melanoma in the nasolacrimal system. Two of the six primary tumours were limbal tumours; the other four were diffuse tumours involving the fornix. In all six patients, the primary conjunctival melanomas were associated with primary acquired melanosis. During the follow-up period (11.6+/-3 years, range 3.4-28.5 years, median 8.7 years) two patients developed metastases and died. CONCLUSIONS: Patients should be advised to contact their treating ophthalmologist in the case of symptoms of epiphora, nose obstructions and epistaxis, especially non-bulbar and diffuse cases associated with primary acquired melanosis. PMID- 20584718 TI - Trends in corneal graft surgery in the UK. AB - AIMS: The aims of this study were to examine trends over time and regional variation in rates of corneal graft surgery in the UK. METHODS: The hospital in patient enquiry (HIPE) and hospital episode statistics (HES) were analysed for keratoplasty admissions in England from 1971 to 2006. NHS Blood and Transplant (NHSBT) data were analysed for keratoplasty operations in the UK from 1999 to 2009. RESULTS: Annual rates of penetrating keratoplasty (PK) under HIPE and HES increased from 0.7 per 100,000 population (1971) to 3.9 (1992), then decreased to 3.1 (2006). Rates of lamellar keratoplasty (LK) increased from 0.1 (1971) to 0.9 (2006). Annual PK operations under NHSBT decreased from 1901 (1999/00) to 1473 (2008/9). Over the same period, deep anterior lamellar keratoplasty operations increased from 91 to 327 per year, while endothelial keratoplasty operations increased from 2 to 569 per year. Geographical analysis showed a wide variation across local authority areas in rates of keratoplasty around 1998-2004, especially for LK. CONCLUSION: The total number of corneal graft operations performed in the UK has increased slowly over the past decade. The proportion of lamellar versus penetrating keratoplasty has increased, with LK performed at the highest rates in specialist centres distributed across the UK. PMID- 20584719 TI - Knowledge, attitude and concerns among urban Malaysian parents of bedwetting children. PMID- 20584720 TI - Sustained happiness? Lack of repetition suppression in right-ventral visual cortex for happy faces. AB - Emotional stimuli have been shown to preferentially engage initial attention but their sustained effects on neural processing remain largely unknown. The present study evaluated whether emotional faces engage sustained neural processing by examining the attenuation of neural repetition suppression to repeated emotional faces. Repetition suppression of neural function refers to the general reduction of neural activity when processing a repeated stimulus. Preferential processing of emotional face stimuli, however, should elicit sustained neural processing such that repetition suppression to repeated emotional faces is attenuated relative to faces with no emotional content. We measured the reduction of functional magnetic resonance imaging signals associated with immediate repetition of neutral, angry and happy faces. Whereas neutral faces elicited the greatest suppression in ventral visual cortex, followed by angry faces, repetition suppression was the most attenuated for happy faces. Indeed, happy faces showed almost no repetition suppression in part of the right-inferior occipital and fusiform gyri, which play an important role in face-identity processing. Our findings suggest that happy faces are associated with sustained visual encoding of face identity and thereby assist in the formation of more elaborate representations of the faces, congruent with findings in the behavioral literature. PMID- 20584721 TI - Previously reappraised: the lasting effect of description type on picture elicited electrocortical activity. AB - To examine whether reappraisal modifies responses to subsequent encounters with stimuli, participants viewed neutral and unpleasant pictures that were preceded by negative or neutral descriptions which served as reappraisal frames. A half an hour later, the same pictures were presented, without preceding frames; EEG was recorded and participants rated each picture on arousal and valence. In line with previous work, unpleasant compared to neutral pictures elicited more positive early- (359 ms), mid- (1074 ms) and late-latency (2436 ms) centrally-distributed ERP components. Pictures previously preceded by negative compared to neutral reappraisal frames were rated as more unpleasant and more emotionally arousing; these pictures elicited a larger mid-latency (1074 ms) occipital positivity. Together, the data suggest that reappraisal exerts an enduring effect on both subjective and neural responses to stimuli. PMID- 20584722 TI - The impact of HLA-DRB alleles on the subclass titres of antibodies against citrullinated peptides. AB - OBJECTIVES: The association between HLA-DR haplotypes and RA have been well established. However, the molecular mechanisms of how HLA mediates susceptibility and/or progression of the disease remain elusive. We therefore turned to the RA specific antibodies directed against citrullinated peptide antigens (ACPAs) and investigated the association between HLA-DRB1 shared epitope (SE) alleles and the IgG subclass titres of cyclic citrullinated peptide (CCP)- and mutated citrullinated vimentin (MCV)-specific antibodies. METHODS: One hundred and twenty seven RA patients were typed for their HLA-DRB1 haplotypes applying low resolution and alleles potentially carrying the SE were sequenced. All patients' sera were analysed by ELISA for the presence of ACPA and 77 patients positive for CCP-specific antibodies were further analysed for the respective IgG subclasses. Subclass titres were then correlated to the presence of a SE. Finally, all patients were screened for the HLA-DRB4-associated splice variant. RESULTS: We found a gene dosage effect of the HLA-DRB1*04-associated SE on both the MCV- and CCP-specific IgG3 levels. The HLA-DRB4-associated splice variant accumulates in ACPA-negative RA patients. CONCLUSIONS: Both the dose-dependent increase in IgG3 among ACPA and the accumulation of the splice variant in ACPA-negative patients imply differential expression of the HLA alleles as the mechanism contributing to the susceptibility and/or disease progression of RA. The preponderance of IgG3 hints at a skewing towards a Th1 response and is reminiscent of increased signal strengths at the immunological synapse. Likewise, the abrogation of HLA-DRB4 expression due to the splice variant reduces the signal strength and seems to protect from ACPA development. PMID- 20584723 TI - Who, and what, causes health inequities? Reflections on emerging debates from an exploratory Latin American/North American workshop. PMID- 20584724 TI - Can exposure to noise affect the 24 h blood pressure profile? Results from the HYENA study. AB - OBJECTIVE; To study the association between exposure to transportation noise and blood pressure (BP) reduction during nighttime sleep. METHODS: 24-h ambulatory BP measurements at 15-min intervals were carried out on 149 persons living near four major European airports. Noise indicators included total and source-specific equivalent indoor noise, total number of noise events, annoyance scores for aircraft and road traffic nighttime noise. Long-term noise exposure was also determined. Multivariate linear regression analysis was applied. RESULTS: The pooled estimates show that the only noise indicator associated consistently with a decrease in BP dipping is road traffic noise. The effect shows that a 5 dB increase in measured road traffic noise during the study night is associated with 0.8% (-1.55, -0.05) less dipping in diastolic BP. Noise from aircraft was not associated with a decrease in dipping, except for a non-significant decrease noted in Athens, where the aircraft noise was higher. Noise from indoor sources did not affect BP dipping. CONCLUSIONS: Road traffic noise exposure may be associated with a decrease in dipping. Noise from aircraft was not found to affect dipping in a consistent way across centres and indoor noise was not associated with dipping. PMID- 20584726 TI - The quality and outcomes framework reduces disparities in health outcomes for cardiovascular disease. PMID- 20584725 TI - Contribution of material, occupational, and psychosocial factors in the explanation of social inequalities in health in 28 countries in Europe. AB - OBJECTIVES: To analyse the associations between socio-economic status (SES), measured using occupation, and self-reported health, and to examine the contribution of various material, occupational and psychosocial factors to social inequalities in health in Europe. METHODS: This study was based on data from the European Quality of Life Survey (EQLS) carried out in 2003. The total sample consisted of 6038 and 6383 working men and women in 28 countries in Europe (response rates: 30.3-91.2%). Each set of potential material, occupational and psychosocial mediators included between eight and 11 variables. Statistical analysis was performed using multilevel logistic regression analysis. RESULTS: Significant social differences were observed for self-reported health, manual workers being more likely to be in poor health (OR=1.89, 95% CI 1.46 to 2.46 for men, OR=2.18, 95% CI 1.71 to 2.77 for women). Strong social gradients were found for almost all potential mediating factors, and almost all displayed significant associations with self-reported health. Social differences in health were substantially reduced after adjustment for material, occupational and psychosocial factors, with material factors playing a major role. The four strongest contributions to reducing these differences were found for material deprivation, social exclusion, financial problems and job reward. Taking all mediators into account led to an explanation of the social differences in health by 78-100% for men and women. CONCLUSION: The association between SES and poor health may be attributed to differential distributions of several dimensions of material, occupational and psychosocial conditions across occupational groups. Interventions targeting different dimensions might result in a reduction in social inequalities in health. PMID- 20584727 TI - Does childhood meat eating contribute to sex differences in risk factors for ischaemic heart disease in a developing population? AB - BACKGROUND: A male epidemic of ischaemic heart disease (IHD) emerges with economic development. It has previously been hypothesised that this epidemic is due to nutritionally driven levels of pubertal sex steroids, which lead to a more atherogenic body shape and lipid profile in boys but not girls, without any sex specific effects on glucose metabolism. This study tests this hypothesis by examining the association of childhood meat eating with IHD risk in a developing Chinese population. METHODS: Multivariable linear and censored regression was used in a cross-sectional study of 19,418 Chinese older (>= 50 years) men and women from the Guangzhou Biobank Cohort Study (phases 2 and 3) to assess the adjusted associations of childhood meat eating with waist to hip ratio (WHR), high-density lipoprotein cholesterol and fasting plasma glucose. RESULTS: Adjusted for age, childhood hunger, life-course socioeconomic position and current lifestyle childhood almost daily meat eating compared with less than weekly meat eating was associated with higher WHR (0.007, 95% CI 0.0003 to 0.01) in men but not women. No association with fasting glucose was observed. CONCLUSIONS: Given the potential limitations of this study, especially the crude nature of the exposure and modest findings, the results should be considered as preliminary. However, they do lend support to the hypothesis that the male epidemic of premature IHD and sexual divergence in IHD rates that occur with economic development may be nutritionally driven in childhood. In elucidating the developmental origins of non-communicable chronic diseases, more attention should be focused on the sociohistorical context and the role of puberty. PMID- 20584728 TI - Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. AB - OBJECTIVES: To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. DESIGN: Population-based follow-up study. SETTING: All children born alive in Denmark 1995-2003. PARTICIPANTS: 588,967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. MAIN OUTCOME MEASURES: A diagnosis of ASD in the Danish Psychiatric Central Register. RESULTS: 33,139 (5.6%) of all children born in Denmark in 1995-2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555,828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4-13 years (median 9 years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. DISCUSSION: This population-based follow-up study found no risk of ASD in children born after assisted conception. PMID- 20584729 TI - Offspring birth weight and risk of mortality from diabetes in mothers. AB - BACKGROUND: Mothers with lower birth weight (LBW) offspring have been found to be associated with cardiovascular disease (CVD) morbidity, which shares many risk factors with diabetes. Aims To investigate the relation between offspring birth weight and maternal risk of mortality from diabetes. METHODS: A total of 1 400 383 singletons of primigravida registered in Taiwan between 1978 and 1987 were followed to the end of 2006. The offspring birth weight was assessed with and without standardisation for the gestational age of offspring. Cox model was used to estimate the HR of maternal diabetes mortality in relation to offspring birth weights. RESULTS: Altogether, 812 (5.8%) mothers died of diabetes. Mothers with LBW (<2500 g) and macrosomia (>4000 g) offspring were both at increased risks of mortality from diabetes with HR 1.76 (95% CI 1.46 to 2.19) and 2.86 (95% CI 2.32 to 3.53), respectively. Similar results were seen while birth weight was standardised for gestational age. CONCLUSIONS: This cohort study found that mothers with LBW and macrosomia offspring had an increased mortality risk of diabetes. This relationship could be attributable to the possible pathway of intergenerational effects or maternal insulin resistance due to maladaptation to pregnancy. PMID- 20584730 TI - Can attending preschool reduce the risk of tobacco smoking in adulthood? The effects of Kindergarten Union participation in South Australia. AB - BACKGROUND: Innovative strategies beyond the health system are required to reduce the prevalence of smoking. Early child development interventions are examples of interventions that can help set children on positive social and educational trajectories, which in turn may also reduce the prevalence of smoking. The aim of this study was to examine the effect of attendance at Kindergarten Union preschools on tobacco smoking in adulthood. METHODS: Kindergarten Union preschools delivered comprehensive services to children and their families, including education, parenting and health services, with a number of features consistent with contemporary ideas of high-quality service delivery. Using a retrospective cohort design with data from the North West Adelaide Health Study, this study examined different aspects of smoking behaviour in adults aged 34-67 years who attended a Kindergarten Union preschool at some stage between 1940 and 1972. Data were analysed using generalised linear model poisson regression with robust variance estimates, adjusting for both child and adult socio-economic factors and history of parental smoking. RESULTS: People who attended preschool had a reduced risk of ever smoking (prevalence ratio 0.87, 95% CI 0.77 to 0.98) and a reduced risk of current smoking in adulthood (prevalence ratio 0.77 (95% CI 0.59 to 1.00)), compared with those who did not attend preschool. There was no effect of preschool attendance on age at smoking uptake, age at quitting or the probability of quitting smoking. CONCLUSION: Attendance at the high-quality Kindergarten Union preschools was associated with a reduction in the initial uptake of smoking and thus the probability of being a current smoker. Among their other potential social benefits, high-quality, universal preschool programmes have the potential to help reduce smoking prevalence across the population. PMID- 20584731 TI - A study on rural-urban differences in neonatal mortality rate in China, 1996 2006. AB - OBJECTIVE: This study examined the differences in neonatal mortality rates between urban and rural areas in China. METHODS AND RESULTS: Data were taken from a database collected by the Chinese surveillance network for mortality of children under 5 years of age. The risk ratio of neonatal mortality for rural versus urban areas was between 2.2 and 2.7 for 1996-2006 and it declined to 2.0 in 2005-6. Pneumonia, birth asphyxia and preterm birth or low birth weight were the major contributors to the urban-rural differences in neonatal mortality, together with a relatively high proportion of home delivery and a relatively lower proportion of hospital treatment in rural areas. CONCLUSION: The urban rural differences reflect the gap between the developed and the underdeveloped regions in China at that period. The neonatal mortality rate in China's rural areas could decrease further if continuous efforts are successful to increase the rates of hospital delivery in rural areas. PMID- 20584732 TI - Socioeconomic differentials in cause-specific mortality among 1.4 million South Korean public servants and their dependents. AB - BACKGROUND: A growing number of investigations have explored the contribution of cause of death to socioeconomic inequalities in mortality in Europe and North America, but few such studies have been performed on Asian populations. OBJECTIVES: To analyse the socioeconomic inequality of cause-specific death rates from both an absolute and relative perspective, and to evaluate the contribution of cause of death to total mortality inequality in South Korea. METHODS: Data were obtained from public servant health insurance beneficiary records. 1,403,297 subjects aged 35-64 years were followed for 9 years. Health insurance premium levels were used as a socioeconomic position indicator. The outcome variables were all-cause, 11 broad causes and 41 specific causes of death. Mortality differentials were examined using cause-specific age-adjusted mortality, relative indices of inequality, and slope inequality indices. RESULTS: Graded inverse associations between income and mortality were found for most, but not all, specific causes of death. The major contributors to income differentials in total mortality in men were liver disease (15.4%), stroke (12.8%), land transport accidents (10.0%), lung cancer (7.1%) and liver cancer (7.0%). In women, stroke (30.7%), diabetes (9.1%), land transport accidents (6.6%), liver cancer (6.0%) and liver disease (5.1%) were important. Conclusions The contribution of the cause of death to socioeconomic inequality in mortality in South Korea differed from Western countries. To develop a policy to reduce the magnitude of socioeconomic inequality, an understanding of the major causes of death that contribute to mortality inequality is required. PMID- 20584733 TI - Body mass index and unintentional weight change associated with all-cause mortality in older Australians: the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA). PMID- 20584734 TI - The perspectives of kidney transplant recipients on medicine taking: a systematic review of qualitative studies. AB - BACKGROUND: Non-adherence to medication regimens after kidney transplantation is a major risk factor for acute rejection and graft loss, yet little is known about the perspectives of kidney transplant recipients on medicine taking. This study aimed to describe the beliefs, experiences and perspectives of kidney transplant recipients on medicine taking. METHODS: We conducted a systematic review of qualitative studies of medicine taking after kidney transplantation. Five electronic databases (to Week 3 of January 2010) were searched. Thematic synthesis of the results and conclusions reported in each included study was performed to develop descriptive and analytical themes. RESULTS: We included seven studies involving 207 participants. The six themes identified were (i) attitudes towards medicine taking, its impact on lifestyle, self-image, relationships and outlook on life; (ii) inadvertent forgetfulness, preoccupation with life commitments; (iii) medication properties; (iv) structure of healthcare services, poor access to pharmacy or affordable medications and conflicting medical appointments; (v) personal efforts in managing medications, organizing and devising strategies for taking medicines on time; and (vi) availability of external social support. These underpinned five reported medicine-taking behaviours including not taking medicines, seeking to change medications or dose, missing a dose, varying the timing of doses and vigilant adherence. CONCLUSIONS: Considering patients' attitudes, priorities, current life events, commitments, support systems and healthcare structures can inform interventions to promote concordance between prescribed medication and medicine-taking behaviours. This may improve treatment outcomes and mitigate the risks of non-adherence-related rejection. PMID- 20584735 TI - Tamoxifen is associated with lower mortality of encapsulating peritoneal sclerosis: results of the Dutch Multicentre EPS Study. AB - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with an increasing incidence. There is no clear consensus on the treatment of EPS, but anecdotal reports indicate improvement in EPS patients treated with tamoxifen. At present, there is no evidence for the effect of tamoxifen treatment in EPS patients. This study investigates the effect of treatment with tamoxifen on survival in EPS patients. METHODS: This study is a retrospective analysis of survival in EPS patients as part of the Dutch multicentre EPS study in the period January 1996 to July 2007. Sixty-three patients with severe EPS were followed up until August 2008. Demographic, patient and PD-related variables of EPS patients were investigated. Patients treated with tamoxifen were compared to patients not treated with tamoxifen. Survival was analysed with multivariate Cox regression analysis. RESULTS: Twenty-four patients were treated with tamoxifen, and 39 were not treated with tamoxifen. The clinical and demographic characteristics were similar for the tamoxifen-treated and non treated groups. The mortality rate was significantly lower in tamoxifen-treated patients compared to EPS patients not treated with tamoxifen (45.8% vs 74.4%, P=0.03). Survival in tamoxifen-treated patients, adjusted for calendar time, age, use of corticosteroids, presence of functioning transplantation, use of parental nutrition and centre influences was longer in comparison to not-treated patients (HR 0.39, P=0.056). CONCLUSIONS: Tamoxifen treatment in EPS patients is associated with lower mortality and shows a trend to an increased multivariate adjusted survival. This supports additional use of tamoxifen to treat patients with severe EPS. PMID- 20584736 TI - Proteome profile of peritoneal effluents in children on glucose- or icodextrin based peritoneal dialysis. AB - BACKGROUND: We compared the proteome profile of peritoneal effluents obtained with icodextrin (Ico) or glucose (Glu) in paediatric patients and defined the oxido-redox status of proteins. METHODS: Sixteen patients underwent two 14-h daytime dwells performed on subsequent days with 7.5% Ico and 3.86% Glu solutions. Protein composition was analysed by two-dimensional electrophoresis and mass spectrometry; oxidized products were evaluated by cyanine labelling. RESULTS: Peritoneal transport kinetics of beta2-microglobulin and cystatin C was linear for both solutions, but was significantly higher with Ico than with Glu, suggesting a better efficiency for these molecules. There was a linear correlation between total protein removal during Ico and Glu dialysis in the same patient, suggesting that it is a function of peritoneal membrane characteristics. The ratio between proteins removed by Ico and by Glu solutions was higher at low removal rate. Image gel analysis revealed 1064 and 774 spots, respectively, in Ico and Glu solutions; 524 were common, and 314 were higher in Ico than Glu effluents. Analysis of protein oxido-redox status showed a greater amount of oxidized albumin in Ico dialysate that was correlated with lower serum levels. CONCLUSIONS: Our results indicate a better efficiency of Ico in removing small proteins. Removal of big proteins and their oxidized isoforms reflects potentially opposite effects. The long-term clinical consequences of removing also potentially important molecules are to be defined. PMID- 20584737 TI - Immunolocalization indicates plasmodesmal trafficking of storage proteins during cambial reactivation in Populus nigra. AB - BACKGROUND AND AIMS: Cambium reactivation after dormancy and budbreak in deciduous trees requires a supply of mobilized reserve materials. The pathway and mode of transfer of these materials are poorly understood. METHODS: Transport of reserve materials during cambium reactivation in Populus nigra was investigated by conventional and immunocytochemical TEM analyses, SDS-PAGE, western blotting and intracellular microinjection of fluorescent dyes. KEY RESULTS: Proteinaceous compounds stored in vacuoles and protein bodies of vascular cells and ray cells disappeared within 3 weeks after cambial reactivation and budbreak. Some of these proteins (32 kDa, 30 kDa and 15 kDa) were labelled by lectin antibodies in SDS PAGE. The same antibodies were localized to plasmodesmata (PDs) between phloem parenchyma, ray cells and fusiform cambial cells. In addition, proteinaceous particles were localized inside the cytoplasmic sleeves of these PDs during budbreak. During this period, the functional diameter of PDs was about 2.2 nm which corresponds approximately to the Stokes' radius of the detected 15-kDa protein. CONCLUSIONS: Lectin-like reserve proteins or their degradation products seem to be transferred through PDs of phloem parenchyma and rays during cambial reactivation and budbreak. PD transfer of storage proteins is a novelty which supports the concept of symplasmic nutrient supply to the cambial region. PMID- 20584738 TI - Fibrinolysis during anaphylaxis, and its spontaneous resolution, as demonstrated by thromboelastography. AB - A large and ever-growing number of agents used in anaesthesia can precipitate acute anaphylactic reactions after their administration. Anaphylaxis is a sudden onset (or rapidly progressive), severe systemic allergic reaction, affecting multiple organ systems. The number of people who suffer severe systemic allergic reactions is increasing. The incidence is about 1-3 reactions per 10 000 population per annum, although anaphylaxis is not always recognized; therefore, certain UK studies may underestimate the incidence. In this case report, we present an episode of acute fibrinolysis associated with life-threatening anaphylaxis, demonstrated by thromboelastography (TEG) and resolving spontaneously. This is despite an added fibrinolytic insult in the form of cardiopulmonary bypass. There is a paucity of literature detailing fibrinolysis occurring during anaphylaxis, most likely due to the limited availability of TEG in the acute setting and the primary clinical focus of delivering life-saving interventions. PMID- 20584739 TI - Extraction of embolized lead tip from azygous vein using distal embolic protection device. AB - Indwelling pacemaker or defibrillator leads are often extracted with use of a cutting laser sheath. We report embolization of a tined pacemaker lead tip into the azygous vein, with the use of a distal embolization protection device to retrieve the fragment. Creative and non-traditional use of a filter-based device may assist in retrieval of embolized material. PMID- 20584740 TI - Implantable electrical devices for prevention of sudden cardiac death: data on implant rates from a 'real world' regional registry. AB - AIMS: International and national consensus guidelines define appropriate indications for implantable cardioverter-defibrillators (ICDs), but the variability in implant rates in 'real world' clinical practice is still unknown. METHODS AND RESULTS: In Emilia-Romagna, an Italian region with around 4.3 million inhabitants, a web-based registry was instituted to collect data for all ICDs implanted. Between January 2006 and December 2008, data from all consecutive patients resident in this region who underwent first implant of an ICD or a biventricular ICD were collected and standardized, considering each regional area (i.e. each of the nine provinces). The overall number of implanted ICDs had an increase in years 2007 and 2008, with a relative increase in comparison to 2006, by 14 and 48% respectively, reaching an average value of 16.2 per 10,000 inhabitants in 2008. Most of the increase was due to a rise in ICDs for primary prevention. The ratio between the implant rates of the provinces with the highest and the lowest implant rates, respectively, was around 2 in 2008. CONCLUSION: Implant rates for ICDs, considering both primary and secondary prevention of sudden death, show up to two-fold variations even in a geographical region where the general level of health care is advanced and well appreciated by the population. The lack of a common strategy for sudden death prevention, approved by both physicians and institutional regional authorities, together with some degree of variability in translating guidelines into clinical practice, were identified as the main factors explaining the heterogeneity in ICD implant rates. PMID- 20584741 TI - Influence of early life factors on social inequalities in psychiatric outcomes among young adult Norwegian men. AB - BACKGROUND: Social inequalities in health can to a substantial degree be explained by social causation. However, indirect selection by early life factors has been suggested. The main aim of this study was to estimate how much adult social gradients in selected psychiatric outcomes depended on parental and individual characteristics in early life. METHODS: The population comprised all males born in Norway 1967-71 (n = 170 678). We compiled data on several social and biological variables from birth onwards from different national registers. Health outcomes were collected from the Cause of Death Register (suicide) and the Labour and Welfare Administration (psychiatric disability, psychiatric sickness absence). Indicator of socio-economic position was education level at the age of 28 years. Men were followed up between 4 and 9 years from the age of 29 years. RESULTS: Crude rates per 100 000 person-years were 21.8 (suicide), 145.7 (disability) and 1164.7 (sickness absence). Social inequalities were strong and consistent for all outcomes. Parental and individual characteristics accounted for a substantial part of the social inequalities in neurosis or personality disorder disability (44.1%) and a moderate role for inequalities in psychiatric sickness absence (25.6%), schizophrenia disability (20.7%) and suicide (17.4%). General ability at the age of 18 years had strongest influence on the social health gradients. Suicide and schizophrenia disability were associated with a combination of high parental and low own education level. CONCLUSION: This study indicates that indirect selection explains a substantial part of social inequalities in certain psychiatric outcomes and that early life prevention is important to reduce health gradients. PMID- 20584742 TI - Characteristics of patients with minor ischaemic strokes and negative MRI: a cross-sectional study. AB - BACKGROUND Diffusion-weighted (DWI) MRI is recommended in UK guidelines to evaluate minor strokes, yet can produce negative results. OBJECTIVE: The authors determined the rate of negative MRI (including DWI) and associated features in patients presenting to hospital with minor strokes. METHODS: The authors performed a prospective observational cross-sectional study in a teaching hospital of patients with a clinical diagnosis of ischaemic lacunar or minor cortical stroke. The authors performed MRI (DWI, T2, fluid-attenuated inversion recovery (FLAIR), T2* and T1) as soon as possible after presentation. The authors used multivariate analysis to determine predictors of negative DWI and MRI (all sequences). Gold standard for clinical diagnosis of stroke was the opinion of an expert panel. RESULTS: The authors recruited 246 patients, mean age 68.1 years (SD 11.6 years), 162 were males (66%), and the median NIHSS was 2 (range 0 to 8). The median time from stroke onset to MR scan was 12 days (IQR 4-27 days). Eighty one patients (33%) did not show any ischaemia on DWI. Sixty patients (24%) did not show the recent infarct on MRI (DWI/T2/FLAIR). With multivariate analysis, less severe stroke, younger age, female gender and increased time from stroke onset to scan were associated with negative DWI. With multivariate analysis, younger age and female gender were associated with negative MRI (DWI or T2 or FLAIR) scans. CONCLUSIONS: There is a high rate of negative MRI and DWI among patients with minor stroke (a third) which has important management and research implications. A negative MRI or DWI does not exclude the diagnosis of stroke. PMID- 20584743 TI - Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activities using two closed-system products. AB - PURPOSE: A preliminary investigation was conducted to evaluate and compare the effectiveness of two closed-system products in preventing contamination of typical pharmacy workplace surfaces with cyclophosphamide during simulated hazardous drug preparation activities in a controlled laboratory setting. METHODS: Two separate trials simulating hazardous drug compounding using cyclophosphamide were performed with two different closed-system products. Prior to each trial, work area surfaces of the biological safety cabinet (BSC) workbench, the BSC airfoil and front grill, and the floor below the BSC were cleaned, and wipe samples were collected and analyzed to determine, if present, levels of cyclophosphamide. Following each trial, wipe samples were collected from the work area surfaces to determine the hazardous drug containment effectiveness of each closed-system product. RESULTS: Cyclophosphamide was not detected on work area surfaces prior to each trial. Low levels were detected on the BSC workbench surface following both trials. DISCUSSION: Based on the limited number of samples obtained during this preliminary study and the determination of the presence of the chemical of interest on the drug vials, no statistical evaluation was performed to compare the relative effectiveness of the two systems tested. Work practices and procedures regarding product operation may affect hazardous drug containment and worker safety. Further study and statistical analyses are needed. PMID- 20584744 TI - Vinflunine: review of a new vinca alkaloid and its potential role in oncology. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, in vitro and in vivo efficacy, and safety profile of vinflunine in the treatment of various solid tumors. DATA SOURCES: A literature search was conducted using keywords included vinflunine, vinca alkaloid, Javlor, and solid tumor in PubMed/MEDLINE (1950 January 2009) and International Pharmaceutical Abstracts (1950-January 2009). STUDY SELECTION AND DATA EXTRACTION: Published studies, posters, and meeting abstracts evaluating the in vitro and in vivo efficacy of vinflunine were reviewed. DATA SYNTHESIS: Vinflunine is the newest member of the vinca alkaloid family. It has the weakest affinity to tubulins, but is shown to have unique receptor-independent antiangiogenesis, and antimetastasis properties. After administration, it is distributed extensively into tissues, metabolized via the CYP3A4 system, and eventually excreted in urine and feces. Phase II/III trials reported activities of vinflunine in advanced stage nonsmall-cell lung cancer, metastatic breast cancer, metastatic renal cell carcinoma, transitional cell carcinomas of the urothelium, small-cell lung cancer, and malignant pleural mesothelioma as monotherapy and in combination with other chemotherapy agents. More ongoing trials are evaluating its use in other solid tumors and in combination regimens. The most common adverse events in these trials were hematological (anemia and neutropenia), constipation, fatigue, abdominal pain, and myalgia. CONCLUSIONS: Vinflunine is a new vinca alkaloid for the treatment of advanced staged solid tumors. Available data showed promising activities in various malignancies. Further studies are needed to further define vinflunine's role in oncology. PMID- 20584745 TI - Alprazolam as an in vivo probe for studying induction of CYP3A in cynomolgus monkeys. AB - Induction of the cytochrome P450 (P450) enzyme is a major concern in the drug discovery processes. To predict the clinical significance of enzyme induction, it is helpful to investigate pharmacokinetic alterations of a coadministered drug in a suitable animal model. In this study, we focus on the induction of CYP3A, which is involved in the metabolism of approximately 50% of marketed drugs and is inducible in both the liver and intestine. As a marker substrate for CYP3A activity, alprazolam (APZ) was selected and characterized using recombinant CYP3A enzymes expressed in Escherichia coli. Both human CYP3A4 and its cynomolgus P450 ortholog predominantly catalyzed APZ 4-hydroxylation with sigmoidal kinetics. When administered intravenously and orally to cynomolgus monkeys, APZ had moderate clearance; its first-pass extraction ratio after oral dosing was estimated to be 0.09 in the liver and 0.45 in the intestine. Pretreatment with multiple doses of rifampicin (20 mg/kg p.o. for 5 days), a known CYP3A inducer, significantly decreased plasma concentrations of APZ after intravenous and oral administrations (0.5 mg/kg), and first-pass extraction ratios were increased to 0.39 in the liver and 0.63 in the intestine. The results were comparable to those obtained in clinical drug-drug interaction (DDI) reports related to CYP3A induction, although the rate of recovery of CYP3A activity seemed to be slower than rates estimated in clinical studies. In conclusion, pharmacokinetic studies using APZ as a probe in monkeys may provide useful information regarding the prediction of clinical DDIs due to CYP3A induction. PMID- 20584746 TI - Population structure, virulence factors and resistance determinants of invasive, non-invasive and colonizing Streptococcus agalactiae in Poland. AB - OBJECTIVES: To analyse Streptococcus agalactiae (group B Streptococcus; GBS) isolates collected in Poland from various human infections and carriage in respect of their clonality, distribution of virulence factors and antimicrobial resistance determinants, including the detection of transposons involved in the dissemination of antimicrobial resistance. METHODS: One hundred and fourteen GBS isolates were analysed by multilocus sequence typing (MLST), serotyping and detection of alp genes of the alpha-like-protein (Alp) family. Determinants of resistance to macrolides and tetracycline, and associated transposons, were detected by PCR and analysed by sequencing. RESULTS: GBS isolates represented 30 different sequence types (STs), grouped in four clonal complexes (CCs), and belonged to seven serotypes. Serotype III was predominant (36.0%), followed by Ia, V, Ib, II, IV and VI. The most common alp genes were rib (26.3%) and alp1/alp5 (23.7%). The bac gene encoding the beta-compound of the surface C protein was present in 17.5% of isolates. Erythromycin resistance (18.4% of isolates) was found in all CCs, but was associated with serotype V and ST1. The most prevalent determinant of resistance was erm(B), usually located on the Tn3872-like transposon. Several changes were observed in the regulatory region of erm(B), some of them resulting in elevated ketolide MICs. Resistance to tetracycline was ubiquitous (91.2%) and its most common determinant was tet(M), occurring in several variants that were typically carried on Tn916-family transposons. CONCLUSIONS: Analysis of bacterial serotypes, alp genes and antimicrobial resistance determinants in the background of MLST-based population structure strengthened evidence of the importance of horizontal gene transfer in GBS evolution. PMID- 20584747 TI - Forgetting of emotional information is hard: an fMRI study of directed forgetting. AB - Strong evidence suggests that memory for emotional information is much better than for neutral one. Thus, one may expect that forgetting of emotional information is difficult and requires considerable effort. The aim of this item method directed forgetting functional magnetic resonance imaging study was to investigate this hypothesis both at behavioral and neural levels. Directed forgetting effects were observed for both neutral and emotionally negative International Affective Picture System images. Moreover, recognition rate of negative to-be-forgotten images was higher than in case of neutral ones. In the study phase, intention to forget and successful forgetting of emotionally negative images were associated with widespread activations extending from the anterior to posterior regions mainly in the right hemisphere, whereas in the case of neutral images, they were associated with just one cluster of activation in the right lingual gyrus. Therefore, forgetting of emotional information seems to be a demanding process that strongly activates a distributed neural network in the right hemisphere. In the test phase, in turn, successfully forgotten images- either neutral or emotionally negative--were associated with virtually no activation, even at the lowered P value threshold. These results suggest that intentional inhibition during encoding may be an efficient strategy to cope with emotionally negative memories. PMID- 20584748 TI - The PI3K-Akt mediates oncogenic Met-induced centrosome amplification and chromosome instability. AB - The oncogenic ability of aberrant hepatocyte growth factor receptor (Met) signaling is thought to mainly rely on its mitogenic and anti-apoptotic effects. Recently, however, cumulating evidences suggest that genomic instability may be a crucial factor in tumorigenesis. Here, we address whether oncogenic Met receptor is linked to the centrosome abnormality and genomic instability. We showed that expression of the constitutive active Met (CA-Met) induced supernumerary centrosomes probably due to deregulated centrosome duplication, which was accompanied with multipolar spindle formation and aneuploidy. Interestingly, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, significantly suppressed the appearance of supernumerary centrosomes. Moreover, knockdown of Akt with small interfering RNAs and overexpression of phosphatase and tensin homolog or dominant-negative Akt abrogated supernumerary centrosome formation, evidencing the involvement of PI3K signaling. We further showed that expression of CA-Met significantly increased aneuploidy in p53(-/-) HCT116 cells, but not in p53(+/+) HCT116 cells, indicating that the ability of CA-Met to induce chromosomal instability (CIN) phenotype is related with p53 status. Together, our data demonstrate that aberrant hepatocyte growth factor/Met signaling induces centrosome amplification and CIN via the PI3K-Akt pathway, providing an example that oncogenic growth factor signals prevalent in a wide variety of cancers have cross talks to centrosome abnormality and CIN. PMID- 20584749 TI - Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF {kappa}B activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of IKK{beta} as a potential target. AB - There are multiple lines of evidence supporting that chronic inflammation is linked to carcinogenesis. Nuclear factor-kappaB (NF-kappaB), a major redox sensitive transcription factor responsible for the induction of a wide array of pro-inflammatory genes, is frequently overactivated in many tumors. Moreover, constitutive activation of IkappaB kinase (IKK), a key regulator of NF-kappaB signaling, has been implicated in inflammation-associated tumorigenesis. Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; PIC) derived from grapes, rhubarb and sugarcane exhibits immunosuppressive and antitumorigenic activities in several cell lines, but the underlying mechanisms are poorly understood. In the present study, we found that PIC inhibited migration and anchorage independent growth of human mammary epithelial cells (MCF-10A) treated with the prototypic tumor promoter, 12-O-tetradecanoylphorbol-13-aceate (TPA). PIC treatment suppressed the TPA-induced activation of NF-kappaB and expression of cyclooxygenase-2 (COX-2) in MCF-10A cells. We speculate that an electrophilic quinone formed as a consequence of oxidation of PIC bearing the catechol moiety may directly interact with critical cysteine thiols of IKKbeta, thereby inhibiting its catalytic activity. In support of this speculation, the reducing agent dithiothreitol abrogated the inhibitory effects of PIC on TPA-induced activation of NF-kappaB signaling and expression of COX-2. In addition, the inhibitory effects of PIC on NF-kappaB activation and COX-2 induction were blunted in cells expressing mutant IKKbeta (C179A) in which cysteine 179 was replaced by alanine. In conclusion, our results show that direct modification of IKKbeta by PIC, presumably at the cysteine 179 residue, blocks NF-kappaB activation signaling and COX-2 induction in TPA-treated MCF-10A cells and also migration and transformation of these cells. PMID- 20584750 TI - Nitric oxide-mediated invasion in Barrett's high-grade dysplasia and adenocarcinoma. AB - Nitric oxide (NO) has been shown to induce double strand DNA breaks in Barrett's oesophagus (BO) and in other cancers has a role in invasion. The specific aims of this study were to investigate whether NO can induce invasion in cells representative of different stages of Barrett's progression and to determine possible underlying mechanisms. Physiological concentrations of NO that mimic luminal production of NO from dietary sources enhanced invasion in cell lines from high-grade dysplasia (GihTERT) and oesophageal adenocarcinoma (FLO) but not a non-dysplastic Barrett's cell line (QhTERT). Real-time reverse transcription polymerase chain reaction revealed that NO induced expression of matrix metalloproteinase (MMP)-1, -3, -7, -9 and -10 and tissue inhibitor of metalloproteinase (TIMP)-1, -2 and -3 in these cell lines. Furthermore, ex vivo treatment of Barrett's biopsy samples with NO induced increases in MMP-1 and TIMP 1 expression, suggesting that NO enhances invasion through deregulating MMP and TIMP expression in epithelial cells. In keeping with these findings, microarray analysis and immunohistochemistry performed on biopsy samples showed enhanced expression of MMP-1, -3, -7 and -10 and TIMP-1 in the progression from non dysplastic BO to adenocarcinoma, although this could not be directly attributed to the effect of NO. Thus, NO may play a role in Barrett's carcinogenesis through deregulating MMP and TIMP expression to enhance invasive potential. PMID- 20584751 TI - Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. AB - Simultaneous exposure of lab animals to toxic doses of the human carcinogen arsenic (As) and the essential trace element selenium (Se) results in a remarkable mutual detoxification. A likely basis for this is the in vivo formation and biliary excretion of seleno-bis(S-glutathionyl) arsinium ion [(GS)(2)AsSe](-); however, the transport protein responsible for the biliary efflux of [(GS)(2)AsSe](-) has not been identified. The multidrug resistance protein 2 (MRP2/ABCC2) is an adenosine triphosphate (ATP)-binding cassette transporter expressed at the canalicular membrane of hepatocytes. Rat Mrp2 is known to excrete the As glutathione (GSH/GS-) conjugates arsenic triglutathione [As(GS)(3)] and monomethyl arsenic diglutathione [CH(3)As(GS)(2)] into bile, and in vitro studies have established As(GS)(3) as a substrate for human MRP2. In the present study, membrane vesicles prepared from human embryonic kidney (HEK293T) cells transfected with human MRP2 were used to demonstrate that MRP2 transports [(GS)(2)AsSe](-). In addition, the characteristics of MRP2 transport of As(GS)(3) and [(GS)(2)AsSe](-) were investigated. As(GS)(3) and [(GS)(2)AsSe](-) are chemically labile and have the potential to dissociate. However, arsenite (As(III)) +/- selenite (Se(IV)) transport was not detected in the absence of GSH or in the presence of the non-reducing GSH analog, ophthalmic acid, suggesting that the conjugates are the transported forms. The apparent K(m) values for [(GS)(2)AsSe](-) and As(GS)(3) were 1.7 and 4.2 microM, respectively, signifying high relative affinities. Membrane vesicles prepared from human erythrocytes, which express the MRP2-related MRP1/ABCC1, MRP4/ABCC4 and MRP5/ABCC5, transported As(GS)(3) in an MRP1- and ATP-dependent manner but did not transport [(GS)(2)AsSe](-). These results have important implications for the Se-dependent and -independent disposition of As. PMID- 20584752 TI - OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization. AB - AIMS: Atherosclerosis is characterized by infiltration of inflammatory cells and enhanced vasa vasorum formation, for which immunological mechanisms may be involved. OX40, a membrane-bound molecule of the tumour necrosis factor-receptor superfamily, is expressed by activated T-cells, while OX40 ligand (OX40L) is expressed in activated macrophages and endothelial cells. In this study, we thus examined whether the OX40/OX40L system is involved in the pathogenesis of atherosclerosis. METHODS AND RESULTS: We examined apolipoprotein E-deficient (ApoE(-/-)) mice and ApoE(-/-)/OX40L-double-deficient (ApoE(-/-)/OX40L(-/-)) mice fed on a high-fat diet for 8 weeks. The extent of aortic atheroma was significantly less in ApoE(-/-)/OX40L(-/-) mice compared with ApoE(-/-) mice. We also treated high-fat-fed ApoE(-/-) mice with or without MGP34 antibody (OX40L specific neutralizing antibody) for 10 weeks. After the treatment, the extent of aortic atheroma was again significantly less in MGP34-treated mice compared with controls. Importantly, both vascular density in the aortic adventitia and vascular endothelial growth factor-induced angiogenesis in the Matrigel assay in vivo were significantly reduced in ApoE(-/-)/OX40L(-/-) mice compared with ApoE( /-) mice. Finally, when high-fat-fed ApoE(-/-) mice were transplanted with bone marrow cells from either wild-type or OX40L(-/-) mice, the extent of aortic atheroma was comparable between the two groups. CONCLUSION: These results indicate that the vascular OX40/OX40L system plays an important role in the formation of vasa vasorum and subsequent atherosclerosis, suggesting that the vascular OX40/OX40L system might be a new therapeutic target of atherosclerosis. PMID- 20584753 TI - Genetic analysis of genes controlling natural variation of seed coat and flower colors in soybean. AB - Soybean exhibits natural variation in flower and seed coat colors via the deposition of various anthocyanin pigments in the respective tissues. Although pigmentation in seeds or flowers has been well dissected at molecular level in several plant species, the genes controlling natural variation in anthocyanin traits in the soybean are not completely understood. To evaluate the genetic correlation between genetic loci and genes, 8 enzyme-encoding gene families and a transcription factor were localized in a soybean genome-wide genetic map. Among the seed coat color-controlling loci, the genetic location of the gene encoding for W1 was substantiated in the context of the current soybean molecular genetic map and O was postulated to correspond to anthocyanidin reductase. Among the genetic loci that regulate flower pigmentation, the genetic locations of the genes encoding for W1, W4, and Wp were identified, W3 was mapped on soybean linkage group B2 (chromosome 14), and W2 was postulated to correspond to an MYB transcription factor. Correlation studies between the developed markers and 3 color-controlling loci provided important empirical data that should prove useful in the design of marker-assisted breeding schemes as well as future association studies involving soybean. PMID- 20584754 TI - Physical activity in the UK: a unique crossroad? PMID- 20584755 TI - The effect of real-time gait retraining on hip kinematics, pain and function in subjects with patellofemoral pain syndrome. AB - BACKGROUND: Patellofemoral pain syndrome (PFPS) is the most common overuse injury in runners. Recent research suggests that hip mechanics play a role in the development of this syndrome. Currently, there are no treatments that directly address the atypical mechanics associated with this injury. OBJECTIVE: The purpose of this study was to determine whether gait retraining using real-time feedback improves hip mechanics and reduces pain in subjects with PFPS. METHODS: Ten runners with PFPS participated in this study. Real-time kinematic feedback of hip adduction (HADD) during stance was provided to the subjects as they ran on a treadmill. Subjects completed a total of eight training sessions. Feedback was gradually removed over the last four sessions. Variables of interest included peak HADD, hip internal rotation (HIR), contralateral pelvic drop, as well as pain on a verbal analogue scale and the lower-extremity function index. We also assessed HADD, HIR and contralateral pelvic drop during a single leg squat. Comparisons of variables of interest were made between the initial, final and 1 month follow-up visit. RESULTS: Following the gait retraining, there was a significant reduction in HADD and contralateral pelvic drop while running. Although not statistically significant, HIR decreased by 23% following gait retraining. The 18% reduction in HADD during a single leg squat was very close to significant. There were also significant improvements in pain and function. Subjects were able to maintain their improvements in running mechanics, pain and function at a 1-month follow-up. An unexpected benefit of the retraining was an 18% and 20% reduction in instantaneous and average vertical load rates, respectively. CONCLUSIONS: Gait retraining in individuals with PFPS resulted in a significant improvement of hip mechanics that was associated with a reduction in pain and improvements in function. These results suggest that interventions for PFPS should focus on addressing the underlying mechanics associated with this injury. The reduction in vertical load rates may be protective for the knee and reduce the risk for other running-related injuries. PMID- 20584756 TI - A comparison of two treatment protocols in the management of exercise-associated postural hypotension: a randomised clinical trial. AB - OBJECTIVE: To investigate which of two commonly used treatment protocols for exercise-associated postural hypotension (EAPH) resulted in earlier discharge from the medical facility. METHODS: This randomised clinical field trial was undertaken at two Ironman Triathlon competitions and one ultra-distance footrace. All collapsed athletes admitted to the medical facilities were considered for the trial. Following clinical assessment and special investigations to confirm the diagnosis of EAPH, 28 athletes were randomly assigned to an oral fluid and Trendelenburg position (OT=14) or an intravenous fluid (IV=14) treatment group. Following admission fluid intake was recorded, and all athletes were assessed clinically (blood pressure, heart rate, level of consciousness) every 15 min until discharge criteria were met. The main measure of outcome was the time to discharge (min). RESULTS: On admission, subjects in the OT and IV groups were similar with respect to age, systolic blood pressure, heart rate and serum sodium concentration. There were no significant differences in heart rate, systolic and diastolic blood pressure between groups and over time until discharge. The fluid intake during the treatment period was significantly greater in the IV group (IV 1045 +/- 185 ml, OT 204 +/- 149 ml; p<0.001). The average time to discharge for the OT group (58 +/- 23 min) was similar to that of the IV group (52.5 +/- 18 min; p=0.47). CONCLUSION: Endurance athletes with EAPH can be treated effectively using the Trendelenburg position and oral fluids and the administration of intravenous fluids does not reduce the time to discharge. The findings of this study support the hypothesis that EAPH is a result of venous pooling due to peripheral vasodilatation, rather than dehydration. PMID- 20584757 TI - Sense of effort and other unpleasant sensations during exercise: clarifying concepts and mechanisms. AB - INTRODUCTION: The sense of effort is an essential component of all forms of exercise. Although extensively studied, exercise physiologists have failed to reach consensus about whether this sensation is based on afferent sensory feedback or is centrally generated and independent of such feedback. This confusion has led to misunderstandings regarding the neurological mechanisms responsible for the sense of effort as opposed to other specific sensations such as pain and temperature. DISCUSSION: A mechanism in which the sense of effort is centrally generated and independent of feedback had been proposed more than 150 years ago. However, a more recent concept of sense of effort as a subjective rating of exercise intensity based on various sensations experienced during exercise given by Borg may have caused confusion, especially among exercise physiologists. Many began to use and understand the sense of effort as a sensation that is generated by afferent sensory feedback. The information reviewed in this article, together with the examples given, constitutes a body of evidence in favour of a centrally generated sense of effort. Afferent sensory feedback is important for the conscious awareness of different sensations such as pain and temperature, and plays important roles in the control of homeostasis. However, peripheral sensory feedback does not seem to be important for the generation of the sense of effort. CONCLUSION: The sense of effort and other specific sensations such as temperature, pain and other muscular sensations present two separate neurological mechanisms. While the former is centrally generated, the latter is based on afferent sensory feedback. An interaction of these sensations is likely the ultimate regulator of exercise performance. However, further investigation is required to fully understand these phenomena. PMID- 20584758 TI - Allergic and non-allergic rhinitis in swimmers: clinical and cytological aspects. AB - BACKGROUND: Rhinitis, either allergic or non-allergic, is frequent in athletes, particularly in swimmers. In this latter case, exposure to chlorine in swimming pools seems to play a relevant role, since it can exacerbate a pre-existing allergic rhinitis (AR) or produce a non-specific irritation. The aim of this study was to detail the clinical and cytological characteristics of rhinitis in swimmers, and to assess the possible role of chlorine-induced symptoms. METHODS: Elite swimmers with rhinitis symptoms underwent a complete diagnostic work-up, including allergy testing, nasal cytology and anterior rhinomanometry. Those evaluations were repeated after 1 month of use of a nasal clip during swimming. A matched group of asymptomatic swimmers was also studied. A total of 74 swimmers (54 symptomatic and 20 controls), with an age range of 9-21 years, were studied. In the control group, only mild and non-specific findings were observed, and only two had a positive skin test. RESULTS: In the symptomatic group, 24 (44%) had AR, and 19 (35%) had a predominant neutrophilic inflammation. The use of a nose clip reduced cellular infiltration and nasal resistances only in the subjects with neutrophilic rhinitis, whereas a clinical improvement was seen also in AR. CONCLUSION: A neutrophilic rhinitis occurs in a large proportion of swimmers. This seems to be irritative in its nature and can be prevented by avoiding the direct contact with chlorinated water. PMID- 20584759 TI - The effect of three different levels of footwear stability on pain outcomes in women runners: a randomised control trial. AB - BACKGROUND: The present study examines the injury status in women runners who are randomised to receive a neutral, stability or motion control running shoe. METHODS: 81 female runners were categorised into three different foot posture types (39 neutral, 30 pronated, 12 highly pronated) and randomly assigned a neutral, stability or motion control running shoe. Runners underwent baseline testing to record training history, as well as leg alignment, before commencing a 13-week half marathon training programme. Outcome measures included number of missed training days due to pain and three visual analogue scale (VAS) items for pain during rest, activities of daily living and with running. RESULTS: 194 missed training days were reported by 32% of the running population with the stability shoe reporting the fewest missed days (51) and the motion control shoe (79) the most. There was a significant main effect (p<0.001) for footwear condition in both the neutral and pronated foot types: the motion control shoe reporting greater levels of pain in all three VAS items. In neutral feet, the neutral shoe reported greater values of pain while running than the stability shoe; in pronated feet, the stability shoe reported greater values of pain while running than the neutral shoe. No significant effects were reported for the highly pronated foot, although this was limited by an inadequate sample size. CONCLUSION: The findings of this study suggest that our current approach of prescribing in-shoe pronation control systems on the basis of foot type is overly simplistic and potentially injurious. PMID- 20584760 TI - Genomic and proteomic responses to environmentally relevant exposures to dieldrin: indicators of neurodegeneration? AB - Dieldrin is a persistent organochlorine pesticide that induces neurotoxicity in the vertebrate central nervous system and impairs reproductive processes in fish. This study examined the molecular events produced by subchronic dietary exposures to 2.95 mg dieldrin/kg feed in the neuroendocrine brain of largemouth bass, an apex predator. Microarrays, proteomics, and pathway analysis were performed to identify genes, proteins, and cell processes altered in the male hypothalamus. Fifty-four genes were induced, and 220 genes were reduced in steady-state levels (p < 0.001; fold change greater than +/- 1.5). Functional enrichment analysis revealed that the biological gene ontology categories of stress response, nucleotide base excision repair, response to toxin, and metabolic processes were significantly impacted by dieldrin. Using isobaric tagging for relative and absolute quantitation, 90 proteins in the male hypothalamus were statistically evaluated for changes in protein abundance. Several proteins altered by dieldrin are known to be associated with human neurodegenerative diseases, including apolipoprotein E, microtubule-associated tau protein, enolase 1, stathmin 1a, myelin basic protein, and parvalbumin. Proteins altered by dieldrin were involved in oxidative phosphorylation, differentiation, proliferation, and cell survival. This study demonstrates that a subchronic exposure to dieldrin alters the abundance of messenger RNAs and proteins in the hypothalamus that are associated with cell metabolism, cell stability and integrity, stress, and DNA repair. PMID- 20584761 TI - Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes. AB - Acetaminophen induces the mitochondrial permeability transition (MPT) in hepatocytes. Reactive oxygen species (ROS) trigger the MPT and play an important role in AAP-induced hepatocellular injury. Because iron is a catalyst for ROS formation, our aim was to investigate the role of chelatable iron in MPT dependent acetaminophen toxicity to mouse hepatocytes. Hepatocytes were isolated from fasted male C3Heb/FeJ mice. Necrotic cell killing was determined by propidium iodide fluorometry. Mitochondrial membrane potential was visualized by confocal microscopy of tetramethylrhodamine methylester. Chelatable ferrous ion was monitored by calcein quenching, and 70 kDa rhodamine-dextran was used to visualize lysosomes. Cell killing after acetaminophen (10mM) was delayed and decreased by more than half after 6 h by 1mM desferal or 1mM starch-desferal. In a cell-free system, ferrous but not ferric iron quenched calcein fluorescence, an effect reversed by dipyridyl, a membrane-permeable iron chelator. In hepatocytes loaded with calcein, intracellular calcein fluorescence decreased progressively beginning about 4 h after acetaminophen. Mitochondria then depolarized after about 6 h. Dipyridyl (20mM) dequenched calcein fluorescence. Desferal and starch desferal conjugate prevented acetaminophen-induced calcein quenching and mitochondrial depolarization. As calcein fluorescence became quenched, lysosomes disappeared, consistent with release of iron from ruptured lysosomes. In conclusion, an increase of cytosolic chelatable ferrous iron occurs during acetaminophen hepatotoxicity, which triggers the MPT and cell killing. Disrupted lysosomes are the likely source of iron, and chelation of this iron decreases acetaminophen toxicity to hepatocytes. PMID- 20584762 TI - Hormonal suppression restores fertility in irradiated mice from both endogenous and donor-derived stem spermatogonia. AB - Irradiation interrupts spermatogenesis and causes prolonged sterility in male mammals. Hormonal suppression treatment with gonadotropin-releasing hormone (GnRH) analogues has restored spermatogenesis in irradiated rats, but similar attempts were unsuccessful in irradiated mice, monkeys, and humans. In this study, we tested a stronger hormonal suppression regimen (the GnRH antagonist, acyline, and plus flutamide) for efficacy both in restoring endogenous spermatogenesis and in enhancing colonization of transplanted stem spermatogonia in mouse testes irradiated with a total doses between 10.5 and 13.5 Gy. A 4-week hormonal suppression treatment, given immediately after irradiation, increased endogenous spermatogenic recovery 1.5-fold, and 11-week hormonal suppression produced twofold increases compared with sham-treated irradiated controls. Furthermore, 10-week hormonal suppression restored fertility from endogenous surviving spermatogonial stem cells in 90% of 10.5-Gy irradiated mice, whereas only 10% were fertile without hormonal suppression. Four- and 11-week hormonal suppression also enhanced spermatogenic development from transplanted stem spermatogonia in irradiated recipient mice, by 3.1- and 4.8-fold, respectively, compared with those not given hormonal treatment. Moreover, the 10-week hormonal suppression regimen, but not a sham treatment, restored fertility of some 13.5-Gy irradiated recipient mice from donor-derived spermatogonial stem cells. This is the first report of hormonal suppression inducing recovery of endogenous spermatogenesis and fertility in a mouse model treated with anticancer agents. The combination of spermatogonial transplantation with hormonal suppression should be investigated as a treatment to restore fertility in young men after cytotoxic cancer therapy. PMID- 20584763 TI - Quantitative expression of RIG-like helicase, NOD-like receptor and inflammasome related mRNAs in humans and mice. AB - The cell-type-, organ- and species-specific expression of the surface and endosomally located Toll-like receptors are well described but little is known about the respective expression profiles of cytosolic pattern recognition molecules. We therefore determined the mRNA expression levels of 15 cytosolic pattern recognition molecules in 11 solid organs of human and mice. Human organs revealed lower mRNA levels of most molecules as in spleen but at least 2-fold higher were inflammasome-related NOD, leucine-rich repeat and pyrin domain containing protein 1-3 (NLRP1-3) and -12 in brain, LGP2, retinoic acid-inducible gene I (RIG-I) and NLRP10 in liver, NLRP10 in small intestine, LGP2, RIG-I, NAIP, NLRP2 and -3 in testis and RIG-I, NLRP2 and -10 in muscle. In mice, most organs also expressed lower mRNA levels compared with spleen. Only NLRP6 in liver, NAIP and NLRP6 in small intestine, LGP2, nucleotide-binding oligomerization domain 1 (NOD1), NLRP1, -2, -6, -10 and -12 in colon and MDA5, RIG-I, NLRC4, NOD1, -2, NLRP1, -2, -6, -10 and -12 mRNA levels in kidney were higher. Resting human and mouse monocytes and T cells expressed most molecules and produced IL-1 beta and CCL5/RANTES upon activation. However, murine monocytes strongly up-regulated, whereas human monocytes down-regulated receptor expression upon activation. These data suggest that the cell-type-, organ- and species-specific expression and regulation need to be considered in the design and interpretation of related studies. PMID- 20584764 TI - Endotoxin tolerance attenuates airway allergic inflammation in model mice by suppression of the T-cell stimulatory effect of dendritic cells. AB - Prior exposure of dendritic cells (DCs) and monocytes/macrophages to LPS causes unresponsiveness to subsequent LPS stimulation, a phenomenon called endotoxin tolerance (ET). ET impairs antigen presentation of these cells to T cells by down regulating expression of MHC class II and co-stimulatory molecules such as CD86 and CD40. Some epidemiological studies have shown that endotoxin acts as a protective factor for allergic diseases. Accordingly, LPS has beneficial effects on the onset of airway allergic inflammation in model animals by T(h)1 skewing or induction of regulatory T cells. However, results derived from asthma model animals are controversial, probably due to the difficulty of handling LPS. We previously generated a monoclonal agonistic antibody against Toll-like receptor (TLR) 4, named UT12, which mimics the biological activities of LPS, exhibiting more potent and sustained ET than does LPS. In this study, we took advantage of UT12 to generate prolonged ET to explore the possibility that ET is involved in the inhibitory effects of the TLR4 signals on asthma model mice. Induction of ET by UT12 inhibited the capacity of DCs to expand ovalbumin (OVA)-specific T(h)2 and T(h)17 cells, without inducing T(h)1 cell or regulatory T-cell populations or producing inhibitory cytokines. Accordingly, administration of UT12 before the OVA sensitization significantly suppressed airway allergic inflammation by OVA inhalation. Taken together, these results demonstrate that ET induced by activating TLR4 signals attenuates airway allergic inflammation through direct suppression of the T-cell stimulatory effect of DCs in asthma model mice. PMID- 20584765 TI - Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. AB - Arenaviruses such as Lassa virus (LASV) cause significant morbidity and mortality in endemic areas. Using a glycoprotein (GP) exchange strategy, we have recently developed live-attenuated arenavirus vaccine prototypes (rLCMV/VSVG) based on lymphocytic choriomeningitis virus (LCMV), a close relative of LASV. rLCMV/VSVG induced long-term CD8(+) T cell immunity against wild-type virus challenge and exhibited a stably attenuated phenotype in vivo. Here we elucidated the innate and adaptive immune requirements for the control of rLCMV/VSVG. Infection of RAG( /-) mice resulted in persisting viral RNA in blood but not in overt viremia. The latter was only found in mice lacking both RAG and IFN type I receptor. Conversely, absence of IFN type II signaling or NK cells on an RAG-deficient background had only minor effects on vaccine virus load or none at all. rLCMV/VSVG infection of wild-type mice induced less type I IFN than did wild-type LCMV, and type I as well as type II IFNs were dispensable for the induction of virus-specific memory CD8 T cells and virus-neutralizing antibodies by rLCMV/VSVG. In conclusion, the adaptive immune systems are essential for elimination of rLCMV/VSVG, and type I but not type II IFN plays a major contributive role in lowering rLCMV/VSVG loads in vivo, attesting to the attenuation profile of the vaccine. Nevertheless, IFNs are not required for the induction of potent vaccine responses. These results provide a better understanding of the immunobiology of rLCMV/VSVG and will contribute to the further development of GP exchange vaccines for combating arenaviral hemorrhagic fevers. PMID- 20584766 TI - Attitudes and barriers to employment in HIV-positive patients. AB - BACKGROUND: Unemployment in the human immunodeficiency virus (HIV) population remains a major issue. Recent changes in the benefits system have triggered concerns about (re)integration into work for adults with HIV. AIMS: To examine attitudes and barriers to employment in HIV patients. METHODS: We undertook a cross-sectional study in the Royal Free HIV outpatient department from December 2008 to February 2009. The questionnaire collected data on demographics, date of HIV diagnosis, combination antiretroviral therapy, CD4 count, employment status, attitudes to work, psychological health and perception of barriers to employment. Logistic regression analyses were used to assess factors associated with not working. RESULTS: Five hundred and forty-five HIV patients took part. Overall, 26% were not working and of these, half (53%) had been unemployed for >5 years. Associations with not working were having been diagnosed with HIV >10 years before, poor psychological health and poor attitudes to employment. There was no association between objective measures of health (CD4 count) and employment status. Those not working were less likely to agree with that 'work is good for physical and mental health' (90 versus 97%: P < 0.01) and more likely to agree that 'should only work if 100% fit and well' (76 versus 51%: P < 0.001) compared to workers. Those currently not working had negative perceptions of their abilities to gain employment and to remain in work. CONCLUSIONS: There are opportunities for HIV services to provide psychological support around attitudes associated with unemployment and to help HIV-positive men in particular obtain and remain in work. PMID- 20584767 TI - Test-retest reliability of the Military Pre-training Questionnaire. AB - BACKGROUND: Musculoskeletal injuries are a significant cause of morbidity during military training. A brief, inexpensive and user-friendly tool that demonstrates reliability and validity is warranted to effectively monitor the relationship between multiple predictor variables and injury incidence in military populations. AIMS: To examine the test-retest reliability of the Military Pre training Questionnaire (MPQ), designed specifically to assess risk factors for injury among military trainees across five domains (physical activity, injury history, diet, alcohol and smoking). METHODS: Analyses were based on a convenience sample of 58 male British Army trainees. Kappa (kappa), weighted kappa (kappa(w)) and intraclass correlation coefficients (ICC) were used to evaluate the 2-week test-retest reliability of the MPQ. For index measures constituting the assessment of a given construct, internal consistency was assessed by Cronbach's alpha (alpha) coefficients. RESULTS: Reliability of individual items ranged from poor to almost perfect (kappa range = 0.45-0.86; kappa(w) range = 0.11-0.91; ICC range = 0.34-0.86) with most items demonstrating moderate reliability. Overall scores related to physical activity, diet, alcohol and smoking constructs were reliable between both administrations (ICC = 0.63 0.85). Support for the internal consistency of the incorporated alcohol (alpha = 0.78) and cigarette (alpha = 0.75) scales was also provided. CONCLUSIONS: The MPQ is a reliable self-report instrument for assessing multiple injury-related risk factors during initial military training. Further assessment of the psychometric properties of the MPQ (e.g. different types of validity) with military populations/samples will support its interpretation and use in future surveillance and epidemiological studies. PMID- 20584769 TI - Cognition and the risk of hospitalization for serious falls in the elderly: results from the Cardiovascular Health Study. AB - BACKGROUND: Many elderly adults fall every year, sometimes resulting in serious injury and hospitalization. Although impaired cognition is a risk factor for injurious falls, little is known about cognitive decline above the threshold of impairment and risk of serious falls in community-dwelling seniors. METHODS: In total, 702 of 5,356 older adults participating in the Cardiovascular Health Study experienced an injurious fall between 1990 and 2005, as indicated by hospitalization records. General cognition was measured annually with the Modified Mini-Mental State Examination and processing speed with the Digit Symbol Substitution Test. The Cox regression model was used to calculate hazard ratio and 95% confidence interval with and without time-dependent covariates and adjusted for known risk factors. RESULTS: Participants with slightly decreased Digit Symbol Substitution Test scores were at increased risk for a serious fall (hazard ratio = 1.58, 95% confidence interval = 1.15-2.17). The risk continued to increase with each quartile decrease in Digit Symbol Substitution Test score. Participants without prevalent cardiovascular disease at baseline and decreased Modified Mini-Mental State Examination scores (80-89) had a 45% increased risk for a serious fall and those at high risk for dementia (<80) were at twice the risk as participants scoring above 90 (hazard ratio = 2.16, 95% confidence interval = 1.60-2.91). CONCLUSIONS: Both decreased general cognition and decreased processing speed appear to be potential risk factors for serious falls in the elderly. When assessing the risk of serious falls in elderly patients, clinicians should consider usual factors like gait instability and sensory impairment as well as less obvious ones such as cardiovascular disease and cognitive function in nondemented adults. PMID- 20584770 TI - Handgrip strength: indications of paternal inheritance in three European regions. AB - BACKGROUND: Handgrip strength is an indicator of overall muscle strength. Poor handgrip strength is a risk factor for disability and mortality. We aimed to investigate the pattern of inheritance of handgrip strength in a sample of parent offspring pairs from three different European regions in Denmark, France, and Italy. METHODS: In this substudy of the European Challenge for Healthy Aging study, handgrip strength was measured in 290 subjects aged 90 years and older and in one of their offspring. RESULTS: When all pairs were considered together, parental and offspring handgrip strength were weakly correlated (r = .16; p < .01). However, paternal-offspring correlation was significantly higher than maternal-offspring correlation (r = .26; confidence interval [CI]: 0.11-0.41 versus r = .03; CI: -0.14 to 0.19; p = .04). This difference was particularly marked for daughters (r = -.07; CI: -0.29 to 0.16 for mother-daughter correlation versus r = .31; CI: 0.11-0.49 for father-daughter; p = .01) compared with sons (r = .12; CI: -0.13 to 0.36 for mother-son correlation versus r = .25; CI: 0.00-0.46 for father-son; p = .47). Father-daughter correlation remained higher than mother daughter when analyses were performed with 144 nondependent parents (r = .32; CI: 0.04; 0.55 versus r = -.25; CI: -0.61 to 0.21; p = .03). These results were similarly observed in the three regions of the study, where mean levels of handgrip strength strongly differed. CONCLUSIONS: It suggests that age-related effects on functional health among women could be mediated more through the paternal line than the maternal. PMID- 20584771 TI - Higher nicotine levels in schizophrenia compared with controls after smoking a single cigarette. AB - INTRODUCTION: The increase in blood nicotine after smoking a single cigarette is nicotine boost. We hypothesized that smokers with schizophrenia (SCZ) have a greater nicotine boost than controls without this disorder. METHODS: Twenty-one subjects (11 SCZ and 10 controls, CON) had repeated venous blood sampling before, during, and after smoking a single cigarette after 12-hr abstinence to measure nicotine concentrations. Blood samples were drawn at baseline (before smoking) and 1, 2, 4, 6, 8, 10, 20, 30, 60, 90, and 120 min after the first puff. Groups were similar in baseline characteristics, including gender and level of dependence, and all smoked 20-30 cigarettes/day. Area under the serum nicotine concentration-time curve (AUC(20)) was calculated for time up to 20 min after the start of smoking. RESULTS: The mean difference in AUC(20) was significantly greater for SCZ versus CON (135.4 ng-min/ml; 95% CI = 0.45-283.80). The shape of the nicotine concentration-time curve for SCZ was significantly different compared with controls (p < .01). Nicotine boost in the first 4 min of smoking was higher in SCZ versus CON (25.2 vs. 11.1 ng/ml, p < .01) with no difference in the total time spent smoking. DISCUSSION: This technique improves on methods, which draw only two blood specimens to assess nicotine intake. Understanding how nicotine boost differs in SCZ from CON may explain high levels of addiction and low success in cessation in smokers with SCZ. PMID- 20584772 TI - The prevalence of multifurcations in tree-space and their implications for tree search. AB - Phylogenetic tree-search is a major aspect of many evolutionary studies. Several tree rearrangement algorithms are available for tree-search, but it is hard to draw general conclusions about their relative performance because many effects are data set specific and can be highly dependent on individual implementations (e.g., RAxML or phyml). Using only the structure of the rearrangements proposed by the Nearest Neighbor Interchange (NNI) algorithm, we show tree-search can prematurely terminate if it encounters multifurcating trees. We validate the relevance of this result by demonstrating that in real data the majority of possible bifurcating trees potentially encountered during tree-search are actually multifurcations, which suggests NNI would be expected to perform poorly. We also show that the star-decomposition algorithm is a special case of two other popular tree-search algorithms, subtree pruning and regrafting (SPR) and tree bisection and reconnection (TBR), which means that these two algorithms can efficiently escape when they encounter multifurcations. We caution against the use of the NNI algorithm and for most applications we recommend the use of more robust tree-search algorithms, such as SPR and TBR. PMID- 20584773 TI - Retroposon insertions provide insights into deep lagomorph evolution. AB - The homogenous mammalian order Lagomorpha comprises about 80 species in two families, Ochotonidae (pikas) and Leporidae (rabbits and hares). However, the phylogenetic relationships among leporids are controversial. Molecular data, particularly from mitochondrial sequences, give highly homoplasious signals. To resolve the controversy between mitochondrial and nuclear data, we analyzed genomic orthologous retroposon insertion sites, a virtually homoplasy-free marker system. From a differential screen of rabbit genomic data for intronic retroposon insertions of CSINE elements, we polymerase chain reaction-amplified and sequenced 11 retroposons in eight representative lagomorphs. We found three retroposons shared among all lagomorphs but absent in outgroups, four confirmed the monophyly of leporids, and three significantly supported Pronolagus as the sister group to all other leporids. One retroposon supported the monophyly of Lepus. The position of Pronolagus outside of the remaining leporids supports the sequence-based signals of nuclear genes and clearly refutes the misleading signals of mitochondrial genes. PMID- 20584774 TI - Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. AB - AIMS: To assess the role of cardiac troponin T (cTnT) levels on admission using a new, highly sensitive assay (hsTnT) in the risk assessment of normotensive patients with acute pulmonary embolism (PE). METHODS AND RESULTS: We prospectively studied 156 consecutive normotensive patients with confirmed PE. The prognostic value of hsTnT at baseline was compared with the conventional cTnT troponin assay and with N-terminal pro-brain natriuretic peptide concentrations. Long-term follow-up was available for 153 patients (98.1%). Highly sensitive troponin T values ranged from 0.001 to 357.2 pg/mL [median 27.2 (25th-75th percentile 9.4-69.4) pg/mL]. Overall, 100 patients (64%) had hsTnT > or =14 pg/mL. Baseline hsTnT was higher in patients with an adverse 30-day outcome (> or =1: death, need for catecholamines, endotracheal intubation, or cardiopulmonary resuscitation) compared with an uncomplicated course [71.7 (35.5-117.9) vs. 26.4 (9.2-68.2) pg/mL; P = 0.027]. The cut-off value of 14 pg/mL showed an excellent prognostic sensitivity and negative predictive value (both 100%). In comparison, as many as 50% of the patients with an adverse early outcome would have been misclassified as low risk by cTnT (cut-off 0.03 ng/mL). Logistic regression indicated a two-fold increase in the risk of an adverse outcome for each increase of hsTnT by 1SD of the natural logarithm (P = 0.037). Patients with elevated hsTnT levels had a reduced probability of long-term survival (P = 0.029 by log rank); by Cox's regression analysis, hsTnT was the only laboratory biomarker predicting an elevated risk of death over the long term. CONCLUSION: Highly sensitive troponin T assays may be capable of improving risk stratification of non-high-risk PE. PMID- 20584775 TI - T-cadherin is present on endothelial microparticles and is elevated in plasma in early atherosclerosis. AB - AIMS: The presence of endothelial cell (EC)-derived surface molecules in the circulation is among hallmarks of endothelial activation and damage in vivo. Previous investigations suggest that upregulation of T-cadherin (T-cad) on the surface of ECs may be a characteristic marker of EC activation and stress. We investigated whether T-cad might also be shed from ECs and in amounts reflecting the extent of activation or damage. METHODS AND RESULTS: Immunoblotting showed the presence of T-cad protein in the culture medium from normal proliferating ECs and higher levels in the medium from stressed/apoptotic ECs. Release of T-cad into the circulation occurs in vivo and in association with endothelial dysfunction. Sandwich ELISA revealed negligible T-cad protein in the plasma of healthy volunteers (0.90 +/- 0.90 ng/mL, n = 30), and increased levels in the plasma from patients with non-significant atherosclerosis (9.23 +/- 2.61 ng/mL, n = 63) and patients with chronic coronary artery disease (6.93 +/- 1.31 ng/mL, n = 162). In both patient groups there was a significant (P = 0.043) dependency of T cad and degree of endothelial dysfunction as measured by reactive hyperaemia peripheral tonometry. Flow cytometry analysis showed that the major fraction of T cad was released into the EC culture medium and the plasma as a surface component of EC-derived annexin V- and CD144/CD31-positive microparticles (MPs). Gain-of function and loss-of-function studies demonstrate that MP-bound T-cad induced Akt phosphorylation and activated angiogenic behaviour in target ECs via homophilic based interactions. CONCLUSION: Our findings reveal a novel mechanism of T-cad dependent signalling in the vascular endothelium. We identify T-cad as an endothelial MP antigen in vivo and demonstrate that its level in plasma is increased in early atherosclerosis and correlates with endothelial dysfunction. PMID- 20584776 TI - Instantaneous coronary collateral function during supine bicycle exercise. AB - AIMS: The instantaneous response of the collateral circulation to isometric physical exercise in patients with non-occlusive coronary artery disease (CAD) is not known. METHODS AND RESULTS: Thirty patients (age 59 +/- 9 years) undergoing percutaneous coronary intervention because of stable CAD were included in the study. Collateral function was determined before and during the last minute of a 6 min protocol of supine bicycle exercise during radial artery access coronary angiography. Collateral flow index (CFI, no unit) was determined as the ratio of mean distal coronary occlusive to mean aortic pressure both subtracted by central venous pressure. To avoid confounding due to recruitment of coronary collaterals by repetitive balloon occlusions, patients were randomly assigned to a group 'rest first' with CFI measurement during rest followed by CFI during exercise, and to a group 'exercise first' with antecedent CFI measurement during exercise before CFI at rest. Simultaneously, coronary collateral conductance (occlusive myocardial blood flow per aorto-coronary pressure drop) was determined by myocardial contrast echocardiography in the last 10 consecutive patients. Overall, CFI increased from 0.168 +/- 0.118 at rest to 0.262 +/- 0.166 during exercise (P = 0.0002). The exercise-induced change in CFI did not differ statistically in the two study groups. Exercise-induced CFI reserve (CFI during exercise divided by CFI at rest) was 2.2 +/- 1.8. Overall, rest to peak bicycle exercise change of coronary collateral conductance was from 0.010 +/- 0.010 to 1.109 +/- 0.139 mL/min/100 mmHg (P < 0.0001); the respective change was similar in both groups. CONCLUSION: In patients with non-occlusive CAD, collateral flow instantaneously doubles during supine bicycle exercise as compared with the resting state. ClinicalTrials.gov Identifier: NCT00947050. PMID- 20584777 TI - Predictors of pregnancy complications in women with congenital heart disease. AB - AIMS: Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited. METHODS AND RESULTS: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome. CONCLUSION: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary. PMID- 20584778 TI - How to calculate vascular age with the SCORE project scales: a new method of cardiovascular risk evaluation. AB - AIMS: In 2008, a new cardiovascular risk table from the Framingham Heart Study was published, which incorporated the new concept 'vascular age'. The aim of the present study was to determine the vascular age calculated from the two SCORE project scales and to determine the degree of agreement in vascular age between the two scales. METHODS AND RESULTS: Vascular age was calculated according to its definition, but using the SCORE scale equations (for low- and high-risk countries) instead of the Framingham equations. Vascular age calculations were obtained covering all the absolute risk values in the SCORE charts, obtaining results of vascular age beyond 65 years of age. To determine the degree of agreement between vascular age calculated with the two SCORE scales (for high- and low-risk countries), the intraclass correlation coefficient was calculated. Of the 400 boxes in the SCORE charts, the vascular age differed between high- and low-risk countries by 1 year or less in 347 boxes (86.75%). In just six boxes (1.5%), the difference was 3 years. Agreement between the scales was very high, as demonstrated by their intraclass correlation coefficient of 0.997. CONCLUSION: Vascular age is a new concept derived from Framingham risk tables that can be calculated with other risk scales, like SCORE. Agreement of vascular age calculated from the SCORE equations for high- and low-risk countries was extremely high, in contrast to the poor agreement in absolute risk. PMID- 20584779 TI - Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran. AB - OBJECTIVE: To evaluate the association between polycyclic aromatic hydrocarbon (PAH) exposure in oesophageal epithelial tissue and oesophageal squamous cell carcinoma (ESCC) case status in an ESCC case-control study in a high-risk population in north-eastern Iran. METHODS: Tissue microarrays (TMAs) of non tumoral oesophageal biopsies from patients with biopsy-proven ESCC and gastrointestinal clinic patients with no endoscopic or biopsy evidence of ESCC (control subjects) in a rural region in north-eastern Iran were immunohistochemically stained. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11 raised against benzo[a]pyrene (B[a]P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis and the average staining in three replicates was calculated. The main outcome measure was adjusted ORs with 95% CIs for the association between antibody staining intensity and ESCC case status. RESULTS: Cultured ESCC cells exposed to B[a]P in vitro showed dose dependent staining with 8E11 but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyse 91 cases and 103 controls. Compared with the lowest quintile of 8E11 staining in the controls, adjusted ORs for the 2nd to 5th quintiles were 2.42, 5.77, 11.3 and 26.6 (95% CI 5.21 to 135), respectively (p for trend <0.001). With 5D11, 89 cases and 101 controls were analysed. No association between staining and case status was observed (ORs for the 2nd to 5th quintiles were 1.26, 0.88, 1.06 and 1.63 (95% CI 0.63 to 4.21), p for trend=0.40). CONCLUSIONS: Dramatically higher levels of 8E11 staining were observed in non-tumoral oesophageal epithelium from patients with ESCC than from control subjects. This finding strengthens the evidence for a causal role for PAHs in oesophageal carcinogenesis in north-eastern Iran. PMID- 20584780 TI - Helicobacter pylori potentiates epithelial:mesenchymal transition in gastric cancer: links to soluble HB-EGF, gastrin and matrix metalloproteinase-7. AB - BACKGROUND AND AIMS: Helicobacter pylori (H pylori) infection is a major risk factor in the development of distal gastric adenocarcinoma. Development of the invasive phenotype is associated with the phenomenon of epithelial:mesenchymal transition (EMT). Soluble heparin-binding epidermal growth factor (HB-EGF) has been implicated in this process. A study was undertaken to investigate the possibility that matrix metalloproteinase (MMP)-7 is upregulated in H pylori infection as a result of hypergastrinaemia, which may enhance shedding of HB-EGF and contribute towards EMT in gastric adenocarcinoma cell lines. METHODS: Three gastric epithelial cell lines (AGS, MGLVA1 and ST16) were co-cultured with the pathogenic H pylori strain 60190 and non-pathogenic strain Tx30a in an in vitro infection model. Gene expression was quantified by real-time PCR, HB-EGF shedding by ELISA and protein expression by immunofluorescence or immunohistochemistry. The INS-GAS mouse, a transgenic mouse model of gastric carcinogenesis which overexpresses amidated gastrin, was used to investigate the in vivo relationship between HB-EGF, MMP-7, gastrin and EMT. RESULTS: The pathogenic strain of H pylori significantly upregulated EMT-associated genes Snail, Slug and vimentin in all three gastric cell lines to a greater degree than the non-pathogenic strain. Pathogenic H pylori also upregulated HB-EGF shedding, a factor implicated in EMT, which was partially dependent on both gastrin and MMP-7 expression. Gastrin and MMP-7 siRNAs and MMP-7 neutralising antibody significantly reduced upregulation of HB-EGF shedding in H pylori infected gastric cell lines and reduced EMT gene expression. The effect of H pylori on EMT was also reversed by gastrin siRNA. Neutralisation of gastrin in the INS-GAS mouse model reduced expression of MMP-7, HB-EGF and key EMT proteins. CONCLUSION: The upregulation of MMP-7 by pathogenic H pylori is partially dependent on gastrin and may have a role in the development of gastric cancer, potentially through EMT, by indirectly increasing levels of soluble HB-EGF. PMID- 20584782 TI - Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. AB - BACKGROUND: Chronic hepatitis C (HCV) infection is associated with diabetes and favourable lipids. OBJECTIVE: To study the effect of this paradox on atherosclerosis and cardiometabolic response to HCV clearance. DESIGN: Cross sectional study. SETTING: Egypt. PARTICIPANTS: 329 chronically infected, 173 with cleared infection and 795 never infected participants aged >or=35 attended for baseline investigations. A subsample of 192, 115 and 187, respectively, underwent ultrasound. MAIN OUTCOME MEASURES: Diabetes, fasting glucose, lipids and fat deposition on ultrasound. Carotid intima-media thickness (IMT) measured atherosclerosis. RESULTS: Diabetes prevalence was raised (10.1% (95% CI 6.6 to 13.6), p=0.04) in HCV chronic, and cleared (10.1% (5.6 to 14.8), p=0.08) individuals versus 6.6% (4.9 to 8.3) in those never infected. Mesenteric fat was raised in chronic (36.4 mm (34.5 to 38.2), p=0.004), and cleared infection (37.8 (35.6 to 40.0), p<0.0001) vs never infected (32.7 (31.0 to 34.4)). LDL cholesterol was lower in chronic (2.69 mmol/l (2.53 to 2.86), p<0.001), but similar in cleared (3.56 (3.34 to 3.78), p=0.4) versus never infected (3.45 (3.30 to 3.60)). Carotid IMT did not differ by infection status: 0.73 (0.70 to 0.76, p=0.4), 0.71 (0.66 to 0.75, p=0.9), 0.71 (0.68 to 0.74), respectively. Adjustment for cardiovascular risk factors increased IMT in chronic infection (0.76 (0.72 to 0.79), p=0.02) versus never infected individuals (0.70 (0.67 to 0.73)). CONCLUSIONS: Hepatic function normalisation with HCV clearance may account for reversal of favourable lipids observed with HCV infection. Hyperglycaemia and visceral adiposity appear less amenable to HCV resolution. These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status. However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection. PMID- 20584783 TI - Loss of GM-CSF signalling in non-haematopoietic cells increases NSAID ileal injury. AB - BACKGROUND: Administration of granulocyte-macrophage colony stimulating factor (GM-CSF) relieves symptoms in Crohn's disease (CD). It has been reported that reduced GM-CSF bioactivity is associated with more aggressive ileal behaviour and that GM-CSF-null mice exhibit ileal barrier dysfunction and develop a transmural ileitis following exposure to non-steroidal anti-inflammatory drugs (NSAIDs). STAT5 signalling is central to GM-CSF action. It was therefore hypothesised that GM-CSF signalling in non-haematopoietic cells is required for ileal homeostasis. METHODS: Bone marrow (BM) chimeras were generated by reconstituting irradiated GM CSF receptor (gm-csfr) beta chain or GM-CSF (gm-csf) deficient mice with wild type BM (WTBM-->GMRKO and WTBM-->GMKO). Intestinal barrier function and the response to NSAID-induced ileal injury were examined. Expression of gm-csf, gm csfr or stat5 in Caco-2 and HT-29 intestinal epithelial cell (IEC) lines was knocked down and the effect of GM-CSF signalling on IEC survival and proliferation was determined. RESULTS: Elevated levels of GM-CSF autoantibodies in ileal CD were found to be associated with dysregulation of IEC survival and proliferation. GM-CSF receptor-deficient mice and WTBM-->GMRKO chimeras exhibited ileal hyperpermeability. NSAID exposure induced a transmural ileitis in GM-CSF receptor-deficient mice and WTBM-->GMRKO chimeras. Transplantation of wild type BM into GM-CSF-deficient mice prevented NSAID ileal injury and restored ileal barrier function. Ileal crypt IEC proliferation was reduced in WTBM-->GMRKO chimeras, while STAT5 activation in ileal IEC following NSAID exposure was abrogated in WTBM-->GMRKO chimeras. Following knock down of gm-csf, gm-csfr alpha or beta chain or stat5a/b expression in Caco-2 cells, basal proliferation was suppressed. GM-CSF normalised proliferation of Caco-2 cells exposed to NSAID, which was blocked by stat5a/b RNA interference. CONCLUSIONS: Loss of GM-CSF signalling in non-haematopoietic cells increases NSAID ileal injury; furthermore, GM-CSF signalling in non-haematopoietic cells regulates ileal epithelial homeostasis via the STAT5 pathway. The therapeutic use of GM-CSF may therefore be beneficial in chronic ileitis associated with CD. PMID- 20584784 TI - Cutting to the chase: circumferential endoscopic mucosal resection for Barrett's neoplasia. PMID- 20584785 TI - Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome. AB - INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable evidence concerning the magnitude of a possible excess risk is necessary to determine whether preventive measures, like screening colonoscopies, in FDRs are justified. AIMS AND METHODS: We analysed the incidence rate of CRC in FDRs and compared this with the general population through person-year analysis after adjustment for demographic characteristics. Population-based incidence data from the Eindhoven Cancer Registry during the period 1970-2006 were used to compare observed numbers of CRC cases in FDRs with expected numbers based on the incidence in the general population. RESULTS: A total of 347 FDRs (41% male) from 57 pedigrees were included, contributing 11 053 person-years of follow-up. During the study period, a total of 27 CRC cases occurred among FDRs compared to five expected CRC cases (p<0.001). The RR of CRC in FDRs compared to the general population was 5.4 (95% CI 3.7 to 7.8). Four FDRs satisfied the criteria for HPS. Based on the estimated HPS prevalence of 1:3000 in the general population the projected RR of HPS in FDRs was 39 (95% CI 13 to 121). CONCLUSIONS: FDRs of HPS patients have an increased risk for both CRC and HPS compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for FDRs seem justified but this needs to be prospectively evaluated. PMID- 20584786 TI - Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells. AB - High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum free or serum-reduced defined medium for adult stem cell cultures. PMID- 20584787 TI - Cytokinin-binding protein (70 kDa) from etioplasts and amyloplasts of etiolated maize seedlings and chloroplasts of green plants and its putative function. AB - Cytokinins regulate chloroplast differentiation and functioning, but their targets in plastids are not known. In this connection, the plastid localization of the 70 kDa cytokinin-binding protein (CBP70) was studied immunocytochemically in 4-d-old etiolated maize seedlings (Zea mays L., cv. Elbrus) using monoclonal antibodies (mAbs) against CBP70 recognizing this protein not only in nuclei and cytoplasm, but also in plastids. CBP70 was detected in the amyloplasts of the root cap and etioplasts of the mesocotyl, stem apex, and leaves encircling the stem axis in the node. Immunogold electron microscopy demonstrated CBP70 localization in amyloplasts outside starch grains and revealed a dependence of CBP70 content in etioplasts on the degree of their inner membrane differentiation: the low CBP70 amount in etioplasts at the early stages of membrane development, the high content in etioplasts with actively developing membranes, and a considerable decrease in plastids with the formed prolamellar body. This suggests that CBP70 is involved in etioplast structure development. CBP70 was also observed in chloroplasts of the bundle sheath of green maize leaves. CBP70 purified from etioplasts mediated trans-zeatin-dependent activation of transcription elongation in vitro in the transcription systems of maize etioplasts and barley chloroplasts, suggesting that CBP70 is a plastid transcription elongation factor or a modulator of plastid elongation factor activity. CBP70 involvement in the cytokinin-dependent regulation of plastid transcription elongation could be essential for the cytokinin control of the biogenesis of this organelle. PMID- 20584788 TI - Remote-controlled stop of phloem mass flow by biphasic occlusion in Cucurbita maxima. AB - The relationships between damage-induced electropotential waves (EPWs), sieve tube occlusion, and stop of mass flow were investigated in intact Cucurbita maxima plants. After burning leaf tips, EPWs propagating along the phloem of the main vein were recorded by extra- and intracellular microelectrodes. The respective EPW profiles (a steep hyperpolarization/depolarization peak followed by a prolonged hyperpolarization/depolarization) probably reflect merged action and variation potentials. A few minutes after passage of the first EPW peak, sieve tubes gradually became occluded by callose, with maximum synthesis occurring approximately 10 min after burning. Early stop of mass flow, well before completion of callose deposition, pointed to an occlusion mechanism preceding callose deposition. This obstruction of mass flow was inferred from the halt of carboxyfluorescein movement in sieve tubes and intensified secretion of aqueous saliva by feeding aphids. The early occlusion is probably due to proteins, as indicated by a dramatic drop in soluble sieve element proteins and a simultaneous coagulation of sieve element proteins shortly after the burning stimulus. Mass flow resumed 30-40 min after burning, as demonstrated by carboxyfluorescein movement and aphid activities. Stop of mass flow by Ca(2+) dependent occlusion mechanisms is attributed to Ca(2+) influx during EPW passage; the reversibility of the occlusion is explained by removal of Ca(2+) ions. PMID- 20584789 TI - Involvement of cytokinins in the grain filling of rice under alternate wetting and drying irrigation. AB - Cytokinins may reflect soil water status and regulate rice (Oryza sativa L.) grain filling. This study investigated the changes in cytokinin levels in rice plants and their relations with grain filling under alternate wetting and drying irrigation. Two 'super' rice cultivars were field grown. Three irrigation regimes, alternate wetting and moderate soil drying (WMD), alternate wetting and severe soil drying (WSD), and conventional irrigation (CI, continuously flooded), were imposed after flowering. No significant differences in grain-filling rate, grain weight, and cytokinin content were observed for the earlier-flowering superior spikelets among the three irrigation regimes. For the later-flowering inferior spikelets, however, their grain-filling rate and grain weight were significantly increased in the WMD and significantly reduced in the WSD when compared with those in the CI. Cytokinin contents in shoots (inferior spikelets and the flag leaves) in the WMD at the soil drying time were comparable with those in the CI, but they were significantly increased when plants were rewatered. The WSD significantly reduced cytokinin contents in the shoot either during soil drying or during the rewatering period. Cytokinin contents in roots showed no significant difference between the WMD and CI regimes. The WSD increased trans-zeatin-type cytokinins, whereas it reduced isopentenyladenine type cytokinins, in roots. Grain-filling rate and grain weight of inferior spikelets were very significantly correlated with cytokinin contents in these spikelets. The results suggest that a post-anthesis WMD holds great promise to improve grain filling of inferior spikelets through elevating cytokinin levels in the rice shoot. PMID- 20584790 TI - Campaigners for full smoking ban in Germany flag up workers' rights. PMID- 20584793 TI - Exercise therapy after corticosteroid injection for moderate to severe shoulder pain: large pragmatic randomised trial. AB - OBJECTIVE: To compare the effectiveness of subacromial corticosteroid injection combined with timely exercise and manual therapy (injection plus exercise) or exercise and manual therapy alone (exercise only) in patients with subacromial impingement syndrome. DESIGN: Pragmatic randomised clinical trial. SETTING: Primary care based musculoskeletal service. Patients Adults aged 40 or over with subacromial impingement syndrome with moderate or severe shoulder pain. INTERVENTIONS: Injection plus exercise or exercise only. MAIN OUTCOME MEASURES: Primary outcome was the difference in improvement in the total shoulder pain and disability index at 12 weeks. RESULTS: 232 participants were randomised (115 to injection plus exercise, 117 to exercise only). The mean age was 56 (range 40 78), 127 were women, and all had had a median of 16 weeks of shoulder pain (interquartile range 12-28). At week 12 there was no significant difference between the groups in change in total pain and disability index (mean difference between change in groups 3.26 (95% confidence interval -0.81 to 7.34), P=0.116). Improvement was significantly greater in the injection plus exercise group at week 1 (6.56, 4.30 to 8.82) and week 6 (7.37, 4.34 to 10.39) for the total pain and disability index (P<0.001), with no differences at week 24 (-2.26, -6.77 to 2.25, P=0.324). CONCLUSIONS: In the treatment of patients with subacromial impingement syndrome, injection plus exercise and exercise only are similarly effective at 12 weeks. Trial registration ISRCT 25817033; EudraCT No 2005-003628 20. PMID- 20584794 TI - Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. PMID- 20584795 TI - Efficacy of prophylactic intravenous calcium administration in first 5 days of life in high risk neonates to prevent early onset neonatal hypocalcaemia: a randomised controlled trial. PMID- 20584796 TI - Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis. AB - Defects of the NKX2-1 gene, encoding thyroid transcription factor-1, cause brain thyroid-lung syndrome (MIM 610978), characterised by benign hereditary chorea, congenital hypothyroidism and respiratory disease. The case of a term infant with mild primary congenital hypothyroidism and neonatal persistent respiratory failure with fatal outcome at 10 months of age despite continuous ventilatory support is described. Congenital defects of genes known to disturb surfactant protein and lipid homeostasis (SFTPB, SFTPC, ABCA3) were excluded. Hypothyroidism prompted sequencing of NKX2-1, which revealed a heterozygous 29 bp deletion (c.278_306del29) disrupting the affected allele. Analysis of bronchoalveolar lavage fluid demonstrated an abnormally low amount of surfactant protein C (SP-C) in relation to SP-B, and low levels of surfactant phospholipids, indicating disturbance of SP and lipid homeostasis as a consequence of NKX2-1 haploinsufficiency. NKX2-1 haploinsufficiency may lead to lethal respiratory failure of the newborn due to disruption of pulmonary surfactant homeostasis. NKX2-1 gene analysis should be considered when investigating irreversible respiratory insufficiency of the newborn. PMID- 20584797 TI - Is cerebral oxygen supply compromised in preterm infants undergoing surgical closure for patent ductus arteriosus? AB - BACKGROUND: A haemodynamically important patent ductus arteriosus (PDA) is a risk factor for brain damage in preterm infants. The authors previously reported lower regional cerebral oxygen saturation (rScO(2)) in infants with PDA, which recovered after administration of indomethacin. However, PDA ligation has been reported to pose an even higher risk of neurodevelopmental impairment. OBJECTIVE: To investigate the impact of surgical closure of PDA on rScO(2) and cerebral fractional tissue oxygen extraction (cFTOE), measured by near-infrared spectroscopy, and on amplitude-integrated electro-encephalography (aEEG) measured brain activity. DESIGN/METHODS: In 20 preterm infants (gestational age 24.7-30.4 weeks; birth weight 630-1540 g), blood pressure, arterial saturation, rScO(2), cFTOE and aEEG were monitored before, during and up to 24 h after surgery. RESULTS: Before surgery, median (range) rScO(2) was 53% (41-68%), and during surgery, but before ductal clipping, it was 46% (31-89%). Eleven infants showed a drop in blood pressure and 13 infants a drop in rScO(2) during surgery (range 2 21%), accompanied by a decrease in aEEG amplitude. Twelve infants had rScO(2) values below 50% during surgery, with five being below 40%. Only at 24 h after surgery was rScO(2) higher (61% (36-85%), p<0.05) and cFTOE values lower (0.38 (0.09-0.61); p<0.05) compared with preclipping values. CONCLUSION: Ductal ligation poses a risk for a further decrease in already compromised cerebral oxygenation in preterm infants. PMID- 20584798 TI - Positive effects of early continuous positive airway pressure on pulmonary function in extremely premature infants: results of a subgroup analysis of the COIN trial. AB - OBJECTIVE: Early continuous positive airway pressure (CPAP) may reduce lung injury in preterm infants. PATIENTS AND METHODS: Spontaneously breathing preterm infants were randomised immediately after birth to nasal CPAP or intubation, surfactant treatment and mechanical ventilation. Pulmonary function tests approximately 8 weeks post-term determined tidal breathing parameters, respiratory mechanics and functional residual capacity (FRC). RESULTS: Seventeen infants received CPAP and 22 mechanical ventilation. Infants with early CPAP had less mechanical ventilation (4 vs 7.5 days; p=0.004) and less total respiratory support (30 vs 47 days; p=0.017). Post-term the CPAP group had lower respiratory rate (41 vs 48/min; p=0.007), lower minute ventilation (223 vs 265 ml/min/kg; p=0.009), better respiratory compliance (0.99 vs 0.82 ml/cm H(2)O/kg; p=0.008) and improved elastic work of breathing (p=0.004). No differences in FRC were found. CONCLUSIONS: Early CPAP is feasible, shortens the duration of respiratory support and results in improved lung mechanics and decreased work of breathing. PMID- 20584799 TI - The management of heroin misuse in pregnancy: time for a rethink? AB - Heroin use in pregnancy is a worldwide problem. Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK. There is, however, increasing evidence of adverse effects upon developing cortical and visual function in children of treated heroin-addicted mothers. The longer-term implications of this are not yet clear, and are confounded by poly drug misuse and ongoing social deprivation. There is a paucity of evidence regarding outcome for infants who require pharmacological treatment for neonatal abstinence syndrome compared to those who have only mild symptoms. Well controlled studies of the treatment of heroin misuse in pregnancy that take account of both neonatal and longer term outcomes for the child are urgently required. PMID- 20584800 TI - An international survey of volume-targeted neonatal ventilation. AB - OBJECTIVE: To evaluate clinical practice of volume-targeted ventilation (VTV). DESIGN: Internet-based survey of all 50 tertiary neonatal units in Australia, New Zealand, Sweden, Denmark, Finland and Norway. RESULTS: Response rate was 100%. VTV was routinely used in 25 (50%) units; 15/25 (60%) in Australasia and 10/25 (40%) in the Nordic countries. The most common reason given for using VTV was that it reduces bronchopulmonary dysplasia (13/25; 52%). The median (IQR) of upper limits of target tidal volume were (1) for initial ventilation of preterm infants with respiratory distress syndrome 5.0 (4.6-6.0) ml/kg and (2) for infants with ventilator-dependent bronchopulmonary dysplasia 6.0 (5.0-8.0) ml/kg. The median (IQR) maximum peak inspiratory pressure limit units were prepared to use in VTV-mode was 35 (30-42.5) cm H(2)O. CONCLUSION: Half of the units used VTV routinely, but with a considerable variation in VTV practice. More studies are required to establish best VTV practice. PMID- 20584801 TI - Transport of premature infants is associated with increased risk for intraventricular haemorrhage. AB - BACKGROUND: Intraventricular haemorrhages (IVH) greatly impact the outcome of very low birth weight (VLBW) infants. This study examines the correlation between inter-hospital transport and the incidence and severity of IVH in VLBW infants in a large cohort of data. METHODS: The US National Inpatient Sample Database (NIS) and its KID subportion were analysed for the years 1997-2004. Infants <1500 g were included in the study and were classified into transport and inborn groups. Groups were further classified according to birth weight into <1000 g and 1000 1499 g. IVH and severe IVH (grades 3-4) were compared between groups and subgroups. Adjusted OR for IVH or severe IVH in correlation with inter-hospital transport were calculated using logistic regression models while controlling for clinical and demographic confounders. We examined changing trends of the incidence of IVH, incidence of neonatal transport and OR for IVH in correlation with neonatal transport in VLBW infants over the years. RESULTS: A total of 67 596 VLBW infants were included in the study. Overall incidence of IVH in the sample was 14.7%; the transport group had more IVH compared to inborn group (27.4% vs 13.42%): adjusted OR 1.75 (95% CI 1.64 to 1.86; p<0.001). Severe IVH was higher in the transport group compared to the inborn group (44.1% vs 32.9%); adjusted OR 1.44 (95% CI 1.22 to 1.70, p=0.001). Similar results were demonstrated in weight-based subgroups. There was increasing trends for neonatal transport and for IVH over the years (p<0.001 for both) with no significant change in the OR for IVH in transported infants. CONCLUSION: Inter-hospital transport of VLBW Infants is correlated with increased incidence and severity of IVH. This correlation has remained constant over the recent years. PMID- 20584802 TI - Nasal trauma due to continuous positive airway pressure in neonates. AB - OBJECTIVE: To evaluate the incidence and severity of nasal trauma secondary to nasal continuous positive airway pressure (nCPAP) in neonates. DESIGN: Prospective observational study. SETTING: Neonatal intensive care unit (NICU) of the University Hospital of Lausanne, Switzerland. PATIENTS: All neonates admitted between January 2002 and December 2007 treated by nCPAP were eligible. METHODS: Patients' noses were monitored during nCPAP. Nasal trauma was reported into three stages: (I) persistent erythema; (II) superficial ulceration; and (III) necrosis. RESULTS: 989 neonates were enrolled. Mean gestational age was 34 weeks (SD 4), mean birth weight 2142 g (SD 840). Nasal trauma was reported in 420 (42.5%) patients and it was of stage I, II and III in 371 (88.3%), 46 (11%) and 3 (0.7%) patients, respectively. Incidence and severity of trauma were inversely correlated with gestational age and birth weight. The risk of nasal trauma was greater in neonates <32 weeks of gestational age (OR 2.48, 95% CI 1.59 to 3.86), weighing <1500 g at birth (OR 2.28, 95% CI 1.43 to 3.64), treated >5 days by nCPAP (OR 5.36, 95% CI 3.82 to 7.52), or staying >14 days in the NICU (OR 1.67, 95% CI 1.22 to 2.28). Most cases of nasal trauma (90%) appeared during the first 6 days of nCPAP. Persistent visible scars were present in two cases. CONCLUSIONS: Nasal trauma is a frequent complication of nCPAP, especially in preterm neonates, but long-term cosmetic sequelae are very rare. This study provides a description of nasal trauma and proposes a simple staging system. This could serve as a basis to develop strategies of prevention and treatment of this iatrogenic event. PMID- 20584803 TI - Non-urgent caesarean delivery increases the need for ventilation at birth in term newborn infants. AB - OBJECTIVE: To compare the need for positive pressure ventilation (PPV) by bag and mask and by bag and endotracheal tube in newly born term infants with vertex presentation delivered by non-urgent caesarean section under regional anaesthesia or non-instrumental vaginal delivery. DESIGN: Cross-sectional study. SETTING: 35 public hospitals in 20 Brazilian state capitals. PATIENTS: 6929 inborn infants without congenital anomalies, with gestational ages from 37(0/7) to 41(6/7) weeks with vertex presentation, born between 1 and 30 September 2003. INTERVENTION: Non urgent caesarean versus non-instrumental vaginal delivery. Non-urgent caesarean was defined as delivery occurring in the absence of prolapsed cord, third trimester haemorrhage, failure of labour induction, fetal distress or non-clear amniotic fluid. MAIN OUTCOME MEASURES: PPV with bag and mask and with bag and endotracheal tube. Both outcomes were adjusted for potential confounding variables by logistic regression analysis. RESULTS: 2087 infants were born by non urgent caesarean and 4842 by non-instrumental vaginal delivery. Non-urgent caesarean delivery under regional anaesthesia compared to vaginal delivery under local or no anaesthesia increased the risk of bag and mask ventilation (OR 1.42, 95% CI 1.07 to 1.89) adjusted for number of gestations, maternal hypertension and birth weight. Ventilation with bag and endotracheal tube was associated only with low birth weight, adjusted for delivery mode and twin gestation. CONCLUSIONS: Term neonates with vertex presentation and clear amniotic fluid born by non urgent caesarean section under regional anaesthesia need to be assisted at birth by health professionals skilled in PPV. PMID- 20584804 TI - Empirical treatment of neonatal sepsis: are the current guidelines adequate? AB - OBJECTIVES: To use national laboratory surveillance data to determine whether pathogens responsible for neonatal bacteraemia were sensitive to nationally recommended antibiotic regimens. DESIGN: All reports of neonatal bacteraemia received by the Health Protection Agency's voluntary surveillance scheme in England and Wales from January 2006 until March 2008, were extracted from the database. Organisms were ranked by frequency, and proportions susceptible to antimicrobials recommended for empirical treatment of neonatal sepsis were determined. RESULTS: There were 1516 reports of bacteraemia for neonates <48 h old (early-onset) and 3482 reports for neonates 2-28 days old (late-onset). For early-onset bacteraemia, group B streptococcus (GBS) was the most frequent pathogen (31%) followed by coagulase-negative staphylococci (CoNS; 22%), non pyogenic streptococci (9%) and Escherichia coli (9%). For late-onset bacteraemia, CoNS were isolated most frequently (45%), followed by Staphylococcus aureus (13%), Enterobacteriaceae (9%), E coli (7%) and GBS (7%). More than 94% of organisms (early-onset) were susceptible to regimens involving combinations of penicillin with either gentamicin or amoxicillin, amoxicillin combined with cefotaxime or cefotaxime monotherapy. More than 95% of organisms (late-onset) were susceptible to gentamicin with either flucloxacillin or amoxicillin and amoxicillin with cefotaxime, but only 79% were susceptible to cefotaxime monotherapy. CONCLUSIONS: Current guidelines for empirical therapy in neonates with sepsis are appropriate. However, gentamicin-based regimens should be used in preference to cefotaxime-based treatments, because of lower levels of susceptibility to cefotaxime and the need to avoid exerting selective pressure for resistance. Surveillance data linked to clinical data should further inform rational antibiotic prescribing in neonatal units. PMID- 20584805 TI - Is remifentanil an option for premedication for neonatal endotracheal intubation? PMID- 20584806 TI - Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis. AB - OBJECTIVE: Osteoarthritis is a global clinical challenge for which no effective disease-modifying agents currently exist. This study identified protease activated receptor 2 (PAR-2) as a novel pathogenic mechanism and potential therapeutic target in osteoarthritis. METHODS: Experimental osteoarthritis was induced in wild-type and PAR-2-deficient mice by sectioning the medial meniscotibial ligament (MMTL), leading to the development of a mild arthropathy. Cartilage degradation and increased subchondral bone formation were assessed as indicators of osteoarthritis pathology. RESULTS: Four weeks following MMTL section, cartilage erosion and increased subchondral bone formation was evident in wild-type mice but was substantially reduced in PAR-2-deficient mice. Crucially, the therapeutic inhibition of PAR-2 in wild-type mice, using either a PAR-2 antagonist or a monoclonal antibody targeting the protease cleavage site of PAR-2, was also equally effective at reducing osteoarthritis progression in vivo. PAR-2 was upregulated in chondrocytes of wild-type but not sham-operated mice. Wild-type mice showed further joint degradation 8 weeks after the induction of osteoarthritis, but PAR-2-deficient mice were still protected. CONCLUSIONS: The substantial protection from pathology afforded by PAR-2 deficiency following the induction of osteoarthritis provides proof of concept that PAR-2 plays a key role in osteoarthritis and suggests this receptor as a potential therapeutic target. PMID- 20584807 TI - Risk of diabetes among patients with rheumatoid arthritis, psoriatic arthritis and psoriasis. AB - OBJECTIVE: To examine the risk of diabetes mellitus (DM) among subjects with rheumatoid arthritis (RA), psoriatic arthritis or psoriasis (PsA/PsO), compared with non-rheumatic controls. METHODS: Study cohorts were assembled using linked healthcare utilisation data from British Columbia. All people with at least two diagnoses of RA or PsA/PsO were included and compared with a cohort of people without any known rheumatic disease. The outcome of interest was a diagnosis of new-onset DM, as defined by initiation of an antidiabetic drug. Incidence rates (IRs) per 1000 person-years and IR ratios were calculated and Cox regression models were constructed to determine the hazard ratio (HR) for diabetes by age, gender, systemic immunosuppressive drug and glucocorticoid use. RESULTS: The study cohort comprised 48 718 subjects with RA, 40 346 with PsA/PsO and 442 033 without any rheumatic disease. The IR for DM among subjects with RA was 8.6 per 1000 person-years (95% CI 8.5 to 8.7), PsA/PsO 8.2 (95% CI 8.1 to 8.3) and for non-rheumatic controls 5.8 (95% CI 5.8 to 5.8). The adjusted HR for RA compared with non-rheumatic controls was 1.5 (95% CI 1.4 to 1.5) and 1.4 (95% CI 1.3 to 1.5) for PsA/PsO. CONCLUSIONS: RA and PsA/PsO appear to be associated with an increased risk of DM. The ability of potent antirheumatic treatments to reverse this trend warrants study. PMID- 20584809 TI - Connection: Schwartz Center Rounds at Massachusetts General Hospital Cancer Center. AB - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center, a nonprofit organization dedicated to supporting and advancing compassionate health care. The Center sponsors Schwartz Rounds, a multidisciplinary forum in which doctors, nurses, chaplains, social workers, and other staff reflect on important psychosocial issues that arise in caring for patients. Attendees participate in an interactive discussion about issues anchored in a case presentation and share their experiences, thoughts, and feelings. The patient narratives may center on wonderful events and transcendent experiences or tragic stories, during which staff can only bear witness to the suffering. The Rounds focus on caregivers' experiences, and encourage staff to share insights, own their vulnerabilities, and support each other. The primary objective is to foster healing relationships and provide support to professional caregivers, enhance communication among caregivers, and improve the connection between patients and caregivers. Currently, >50,000 clinicians attend monthly Schwartz Rounds at 195 sites in 31 states, numbers that are rapidly growing. In this article we explore the reasons that contribute to the success of this model of multidisciplinary reflection. PMID- 20584810 TI - Measuring circulating miRNAs: the new "PSA" for Breast Cancer? PMID- 20584811 TI - Chryseobacterium xinjiangense sp. nov., isolated from alpine permafrost. AB - Strain TSBY 67(T) was isolated during a study on the phylogenetic diversity of culturable bacteria from alpine permafrost in Tianshan Mountains, China. On the basis of 16S rRNA gene sequence analysis, strain TSBY 67(T) was closely related to members of the genus Chryseobacterium and exhibited 96.8 % 16S rRNA gene sequence similarity to Chryseobacterium aquaticum 10-46(T) and Chryseobacterium soldanellicola PSD 1-4(T). Strain TSBY 67(T) grew aerobically, at 4-37 degrees C, with 0-2 % NaCl and at pH 6-8. Cells were Gram-staining negative, non-motile and non-spore-forming rods. The dominant cellular fatty acids were iso-C(15 : 0) (26.9 %), iso-C(17 : 0) 3-OH (16.1 %) and iso-C(17 : 1)omega9c (15.4 %). The G+C content of the DNA was 33.5 mol%. Strain TSBY 67(T) was distinguishable from its closest phylogenetic neighbours by a combination of phenotypic characteristics. Therefore, strain TSBY 67(T) represents a novel species of the genus Chryseobacterium, for which the name Chryseobacterium xinjiangense sp. nov. is proposed. The type strain is TSBY 67(T) ( = NRRL B-51308(T) = CCTCC AB 207183(T)). PMID- 20584812 TI - Caldilinea tarbellica sp. nov., a filamentous, thermophilic, anaerobic bacterium isolated from a deep hot aquifer in the Aquitaine Basin. AB - An anaerobic, thermophilic, filamentous (0.45 * >100 um) bacterium, designated D1 25-10-4(T), was isolated from a deep hot aquifer in France. Cells were non-motile and Gram-negative. Growth was observed at 43-65 degrees C (optimum 55 degrees C), at pH 6.8-7.8 (optimum pH 7.0) and with 0-5 g NaCl l(-1) (optimum 0 g NaCl l( 1)). Strain D1-25-10-4(T) was a chemo-organotroph and fermented ribose, maltose, glucose, galactose, arabinose, fructose, mannose, sucrose, raffinose, xylose, glycerol, fumarate, peptone, starch and xylan. Yeast extract was required for growth. Sulfate, thiosulfate, sulfite, elemental sulfur, nitrate, nitrite and fumarate were not used as terminal electron acceptors. The G+C content of the DNA was 61.9 mol%. The major cellular fatty acids of strain D1-25-10-4(T) were C(17 : 0), C(18 : 0,) C(16 : 0) and iso-C(17 : 0). The closest phylogenetic relative of strain D1-25-10-4(T) was Caldilinea aerophila STL-6-O1(T) (97.9 % 16S rRNA gene sequence similarity). DNA-DNA relatedness between strain D1-25-10-4(T) and Caldilinea aerophila DSM 14535(T) was 8.7 +/- 1 %. On the basis of phylogenetic, genotypic and phenotypic characteristics, strain D1-25-10-4(T) represents a novel species within the genus Caldilinea, class Caldilineae, phylum Chloroflexi, for which the name Caldilinea tarbellica sp. nov. is proposed. The type strain is D1 25-10-4(T) ( = DSM 22659(T) = JCM 16120(T)). PMID- 20584813 TI - Bacillus luteolus sp. nov., a halotolerant bacterium isolated from a salt field. AB - A novel Gram-stain-positive, motile, strictly aerobic bacterium, designated YIM 93174(T), was isolated from a salt field in Korea. Cells of this strain were rod shaped and formed pale tangerine colonies and grew at pH 6.0-8.0 (optimal growth at pH 7.0), at 15-45 degrees C (optimum 28-37 degrees C) and at salinities of 0 10 % (w/v) NaCl (optimum 0-2 % NaCl). Some phenotypic characters allowed differentiation of strain YIM 93174(T) from its nearest phylogenetic relatives. Comparative 16S rRNA gene sequence analysis showed that strain YIM 93174(T) belongs to the genus Bacillus, exhibiting the highest level of sequence similarity with the type strain of Bacillus humi (95.7 %), followed by those of Bacillus alkalitelluris (94.9 %) and Bacillus litoralis (94.5 %). The major fatty acids were iso-C(15 : 0), anteiso-C(15 : 0) and iso-C(16 : 0). The cell-wall peptidoglycan was of the A1gamma type, containing meso-diaminopimelic acid as the diagnostic diamino acid. The genomic DNA G+C content was 36.9 mol% and the predominant respiratory quinone was MK-7. The major polar lipids of strain YIM 93174(T) were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and two unknown phospholipids. On the basis of the evidence from this polyphasic study, strain YIM 93174(T) represents a novel species of the genus Bacillus, for which the name Bacillus luteolus sp. nov. is proposed, with YIM 93174(T) ( = DSM 22388(T) = KCTC 13210(T) = CCTCC AA 208068(T)) as the type strain. PMID- 20584808 TI - A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. AB - Rapidly growing insights into the molecular biology of colorectal cancer (CRC) and recent developments in gene sequencing and molecular diagnostics have led to high expectations for the identification of molecular markers to be used in optimized and tailored treatment regimens. However, many of the published data on molecular biomarkers are contradictory in their findings and the current reality is that no molecular marker, other than the KRAS gene in the case of epidermal growth factor receptor (EGFR)- targeted therapy for metastatic disease, has made it into clinical practice. Many markers investigated suffer from technical shortcomings, resulting from lack of quantitative techniques to capture the impact of the molecular alteration. This understanding has recently led to the more comprehensive approaches of global gene expression profiling or genome-wide analysis to determine prognostic and predictive signatures in tumors. In this review, an update of the most recent data on promising biological prognostic and/or predictive markers, including microsatellite instability, epidermal growth factor receptor, KRAS, BRAF, CpG island methylator phenotype, cytotoxic T lymphocytes, forkhead box P3-positive T cells, receptor for hyaluronic acid mediated motility, phosphatase and tensin homolog, and T-cell originated protein kinase, in patients with CRC is provided. PMID- 20584815 TI - Paenibacillus phoenicis sp. nov., isolated from the Phoenix Lander assembly facility and a subsurface molybdenum mine. AB - A novel Gram-positive, motile, endospore-forming, aerobic bacterium was isolated from the NASA Phoenix Lander assembly clean room that exhibits 100 % 16S rRNA gene sequence similarity to two strains isolated from a deep subsurface environment. All strains are rod-shaped, endospore-forming bacteria, whose endospores are resistant to UV radiation up to 500 J m(-2). A polyphasic taxonomic study including traditional phenotypic tests, fatty acid analysis, 16S rRNA gene sequencing and DNA-DNA hybridization analysis was performed to characterize these novel strains. The 16S rRNA gene sequencing convincingly grouped these novel strains within the genus Paenibacillus as a separate cluster from previously described species. The similarity of 16S rRNA gene sequences among the novel strains was identical but only 98.1 to 98.5 % with their nearest neighbours Paenibacillus barengoltzii ATCC BAA-1209(T) and Paenibacillus timonensis CIP 108005(T). The menaquinone MK-7 was dominant in these novel strains as shown in other species of the genus Paenibacillus. The DNA-DNA hybridization dissociation value was <45 % with the closest related species. The novel strains had DNA G+C contents of 51.9 to 52.8 mol%. Phenotypically, the novel strains can be readily differentiated from closely related species by the absence of urease and gelatinase and the production of acids from a variety of sugars including l-arabinose. The major fatty acid was anteiso-C(15 : 0) as seen in P. barengoltzii and P. timonensis whereas the proportion of C(16 : 0) was significantly different from the closely related species. Based on phylogenetic and phenotypic results, it was concluded that these strains represent a novel species of the genus Paenibacillus, for which the name Paenibacillus phoenicis sp. nov. is proposed. The type strain is 3PO2SA(T) ( = NRRL B-59348(T) = NBRC 106274(T)). PMID- 20584814 TI - Ignatzschineria indica sp. nov. and Ignatzschineria ureiclastica sp. nov., isolated from adult flesh flies (Diptera: Sarcophagidae). AB - Two Gram-negative-staining, aerobic, non-motile, rod-shaped bacteria, designated strains FFA1(T) and FFA3(T), and belonging to the class Gammaproteobacteria were isolated from the gastrointestinal tract of adult flesh flies (Diptera: Sarcophagidae). Phylogenetic analysis of 16S rRNA gene sequence data placed these two strains within the genus Ignatzschineria with similarities of 98.6 % (FFA1(T)) and 99.35 % (FFA3(T)) to Ignatzschineria larvae L1/68(T). The level of gene sequence similarity between strains FFA1(T) and FFA3(T) was 99 %, 97.15 % and 78.1 % based on the 16S rRNA, 23S rRNA and gyrB gene sequences, respectively. Strains FFA1(T) and FFA3(T) shared 24 % DNA-DNA relatedness. DNA-DNA hybridization revealed a very low level of relatedness between the novel strains (22 % for strain FFA1(T) and 44 % for strain FFA3(T)) and I. larvae L1/68(T) genomic DNA. The respiratory quinone was Q-8 in both novel strains. The DNA G+C contents were 41.1 mol% and 40.1 mol% for strains FFA1(T) and FFA3(T), respectively. The cell membrane of both strains consisted of phosphatidylglycerol, phosphatidylethanolamine, phospholipids and aminophospholipid. The major fatty acids for both strains were C(16 : 0), summed feature 8 (C(18 : 1)omega7c and/or C(18 : 1)omega6c), CyC(19 : 0)omega8c and C(14 : 0). The results of DNA-DNA hybridization between the two new strains and I. larvae L1/68(T), in combination with phylogenetic, chemotaxonomic, biochemical and electron microscopic data, demonstrated that strains FFA1(T) and FFA3(T) represented two novel species of the genus Ignatzschineria for which the names Ignatzschineria indica sp. nov. (type strain FFA1(T) = DSM 22309(T) = KCTC 22643(T) = NCIM 5325(T)) and Ignatzschineria ureiclastica sp. nov. (type strain FFA3(T) = DSM 22310(T) = KCTC 22644(T) = NCIM 5326(T)) are proposed. PMID- 20584816 TI - Alcanivorax pacificus sp. nov., isolated from a deep-sea pyrene-degrading consortium. AB - A taxonomic study was carried out on a novel bacterial strain, designated W11 5(T), which was isolated from a pyrene-degrading consortium enriched from deep sea sediment of the Pacific Ocean. The isolate was Gram-reaction-negative and oxidase- and catalase-positive. Growth was observed in 0.5-12 % (w/v) NaCl and at 10-42 degrees C. On the basis of 16S rRNA gene sequence analysis, strain W11 5(T) was shown to belong to the genus Alcanivorax with a close relation to A. dieselolei B-5(T) (93.9 % 16S rRNA sequence similarity), A. balearicus MACL04(T) (93.1 %), A. hongdengensis A-11-3(T) (93.1 %), A. borkumensis SK2(T) (93.0 %), A. venustensis ISO4(T) (93.0 %) and A. jadensis T9(T) (92.9 %). Similarities between the gyrB gene sequences of W11-5(T) and other species of the genus Alcanivorax were between 76.8 and 80.8 %. The principal fatty acids were C(12 : 0) 3-OH (8.0 %), C(16 : 0) (29.1 %) and C(18 : 1)omega7c (27.4 %). The G+C content of the chromosomal DNA was 60.8 mol%. Based on its morphology, physiology and fatty acid composition as well as the results of 16S rRNA and gyrB gene sequence analyses, strain W11-5(T) ( = MCCC 1A00474(T) = CCTCC AB 208236(T) = LMG 25514(T)) represents a novel species of the genus Alcanivorax, for which the name Alcanivorax pacificus sp. nov. is proposed. PMID- 20584818 TI - Nevskia terrae sp. nov., isolated from soil. AB - A Gram-negative bacterium, designated KIS13-15(T), was isolated from soil in Korea. Cells were strictly aerobic rods and were motile with 1-3 subpolar flagella. 16S rRNA gene sequence analysis revealed that strain KIS13-15(T) belonged to the order Xanthomonadales of the class Gammaproteobacteria and was closely related to Nevskia soli GR15-1(T) (97.9 % 16S rRNA gene sequence similarity) and Nevskia ramosa Soe1(T) (96.8 %). Strain KIS13-15(T) exhibited 38 and 29 % DNA-DNA relatedness with N. soli KACC 11703(T) and N. ramosa DSM 11499(T), respectively. The major fatty acids (>10 % of the total) were C(18 : 1)omega7c (40.6 %) and C(16 : 0) (12.4 %). The major isoprenoid quinone was ubiquinone 8. DNA G+C content was 67.3 mol%. The phenotypic characterization combined with 16S rRNA gene sequence analysis and DNA-DNA hybridization clearly classified strain KIS13-15(T) in a novel species of the genus Nevskia, for which the name Nevskia terrae sp. nov. is proposed. The type strain is KIS13-15(T) ( = KACC 12736(T) = JCM 15425(T)). PMID- 20584817 TI - Rhizobium rosettiformans sp. nov., isolated from a hexachlorocyclohexane dump site, and reclassification of Blastobacter aggregatus Hirsch and Muller 1986 as Rhizobium aggregatum comb. nov. AB - A Gram-negative, rod-shaped, motile, aerobic bacterial strain, W3(T), was isolated from hexachlorocyclohexane (HCH)-contaminated groundwater from Lucknow, India, and its taxonomic position was determined using a polyphasic approach. Strain W3(T) shared highest 16S rRNA gene sequence similarity of 97.8 % with Rhizobium selenitireducens B1(T), followed by Rhizobium daejeonense L61(T) (97.7 %), Rhizobium radiobacter ATCC 19358(T) (97.5 %) and Blastobacter aggregatus IFAM 1003(T) (97.2 %). Strain W3(T) formed a monophyletic clade with Blastobacter aggregatus IFAM 1003(T) ( = DSM 1111(T)) in the cluster of species of the genus Rhizobium. Phylogenetic analyses of strain W3(T) using atpD and recA gene sequences confirmed the phylogenetic arrangements obtained by using 16S rRNA gene sequences. Hence, the taxonomic characterization of B. aggregatus DSM 1111(T) was also undertaken. Strains W3(T) and B. aggregatus DSM 1111(T) contained summed feature 8 (18 : 1omega7c and/or 18 : 1omega6c; 65.4 and 70.8 %, respectively) as the major fatty acid, characteristic of the genus Rhizobium. DNA-DNA relatedness of strain W3(T) with Rhizobium selenitireducens LMG 24075(T), Rhizobium daejeonense DSM 17795(T), Rhizobium radiobacter DSM 30147(T) and B. aggregatus DSM 1111(T) was 42, 34, 30 and 34 %, respectively. The DNA G+C contents of strain W3(T) and B. aggregatus DSM 1111(T) were 62.3 and 62.7 mol%, respectively. A nifH gene encoding dinitrogenase reductase was detected in strain W3(T) but not in B. aggregatus DSM 1111(T). Based on the results obtained by phylogenetic and chemotaxonomic analyses, phenotypic characterization and DNA-DNA hybridization, it is concluded that strain W3(T) represents a novel species of the genus Rhizobium, for which the name Rhizobium rosettiformans sp. nov. is proposed (type strain W3(T) = CCM 7583(T) = MTCC 9454(T)). It is also proposed that Blastobacter aggregatus Hirsch and Muller 1986 be transferred to the genus Rhizobium as Rhizobium aggregatum comb. nov. (type strain IFAM 1003(T) = DSM 1111(T) = ATCC 43293(T)). PMID- 20584819 TI - Halomonas vilamensis sp. nov., isolated from high-altitude Andean lakes. AB - A Gram-stain-negative, aerobic, rod-shaped, non-spore-forming bacterium (SV325(T)) was isolated from the sediment of a hypersaline lake located 4600 m above sea level (Laguna Vilama, Argentina). Strain SV325(T) formed cream to pink colonies, was motile and moderately halophilic, and tolerated NaCl concentrations of 1-25 % (w/v) with an optimum of 5-10 % (w/v). Growth occurred at 5-40 degrees C (optimum around 30 degrees C) and at pH 5.0-10.0 (optimum 7.0-8.0). The bacterium did not produce exopolysaccharides and stained positively for intracellular polyphosphate granules but not for poly-beta-hydroxyalkanoates. It produced catalase and oxidase, reduced nitrate to nitrite, hydrolysed gelatin, did not produce acids from sugars and utilized a limited range of substrates as carbon and energy sources: acetate, caproate, fumarate, dl-beta-hydroxybutyrate, malate, maleate, malonate and succinate. The predominant ubiquinones were Q-9 (92.5 %) and Q-8 (7.5 %), the major fatty acids were C(19 : 0) cyclo omega8c, C(16 : 0), C(17 : 0) cyclo and C(16 : 1)omega7c/iso-C(15:0) 2-OH, and the DNA G+C content was 55.0 mol%. Phylogenetic analyses based on the 16S rRNA gene indicated that strain SV325(T) belongs to the genus Halomonas in the class Gammaproteobacteria. Physiological and biochemical tests allowed phenotypic differentiation of strain SV325(T) from closely related species with validly published names. We therefore propose a novel species, Halomonas vilamensis sp. nov., with type strain SV325(T) ( = DSM 21020(T) = LMG 24332(T)). PMID- 20584820 TI - Test-retest reliability of isokinetic strength and endurance tests in patients with intermittent claudication. AB - The objective was to determine the reliability of isokinetic strength and endurance testing in the ankle joints of patients with intermittent claudication. Twenty-three patients with peripheral artery disease (PAD) and symptoms of intermittent claudication participated in the study. Isokinetic strength and endurance testing of the ankle joint were performed in symptomatic and asymptomatic legs on 3 separate days. Intraclass coefficient correlation of peak torque (PT) and total work (TW) ranged from 0.77 to 0.92 and 0.89 to 0.96, respectively. PT and TW increased significantly and similarly in both legs from day 1 to day 2 (PT: +42 +/- 84% in the symptomatic leg and +33 +/- 51% in the asymptomatic leg, p < 0.05;TW: +38 +/- 26% in the symptomatic leg and +26 +/- 50% in the asymptomatic leg, p < 0.05). In conclusion, isokinetic strength and endurance testing in the ankle joints of patients with PAD presents reliability coefficients ranging from 0.77 to 0.96. However, strength and endurance increased between the first and the other test sessions performed on separate days, suggesting that two test sessions are necessary for the accurate evaluation of strength and endurance in patients with PAD. PMID- 20584821 TI - Chronic atherosclerotic mesenteric ischemia (CMI). AB - Chronic mesenteric ischemia (CMI) is most likely caused by atherosclerosis and less frequently by external compression and vasculitis. Symptomatic CMI is an uncommon, potentially under-diagnosed condition caused by fixed stenoses or occlusion of, in most conditions, at least two visceral arteries. If only one of the three major bowel-providing arteries - the celiac trunk, and the superior and inferior mesenteric arteries - is affected, the patient is usually asymptomatic due to a tight collateral network. The only exception is the celiac artery compression syndrome which represents primarily a compression syndrome of celiac plexus nerves by the arcuate ligament in conjunction with a compression of the celiac trunk. CMI of atherosclerotic origin is associated with a high morbidity and mortality. During the last decade, endovascular revascularization has replaced surgical revascularization as the therapy of choice in most centers. This article reviews the most relevant clinical aspects of the disease and the current practice of diagnosis and treatment of CMI. PMID- 20584822 TI - Inconclusive evidence regarding the volume of gastric aspirate that can be safely reintroduced following residual volume measurements. PMID- 20584823 TI - Available evidence insufficient to assess safety and effectiveness of flu vaccines for older people. PMID- 20584824 TI - Insufficient evidence to recommend routine adjunctive chest physiotherapy for adults with pneumonia. PMID- 20584825 TI - Nurse practitioner provided home telemonitoring and medication management improves glycemic control in primary care patients with type 2 diabetes more than monthly care coordination telephone call. PMID- 20584826 TI - Evidence remains lacking that vaccinating healthcare workers prevents influenza in elderly residents in long-term care. PMID- 20584827 TI - Prophylactic paracetamol at the time of infant vaccination reduces the risk of fever, but also reduces antibody response. PMID- 20584828 TI - Prevalence of myocardial infarction over a 10-15-year period in the USA has decreased in midlife men but increased in women, with a decrease in the excess cardiovascular risk of men compared with women. PMID- 20584829 TI - Prevalence of undiagnosed urinary incontinence in women is 53% in the preceding year and 39% in the preceding week in a US managed-care population. PMID- 20584830 TI - 13% of parents of children who died of cancer considered requesting hastened death for their child: this was more likely if their child was in pain. PMID- 20584831 TI - Almost a fifth of children admitted to Dutch hospitals have acute or chronic malnutrition; risk factors include underlying disease and non-white ethnicity. PMID- 20584832 TI - Wound prevalence in community care settings in Ireland ranges from 2.7% in prisons to 33.5% in intellectual disability services, with pressure ulcers, leg ulcers, self-inflicted abrasions and surgical wounds the most common. PMID- 20584833 TI - Two types of exercise programme for institutionalised older people may preserve the ability to perform some activities of daily living. PMID- 20584834 TI - Higher physical activity during middle age is associated with increased odds of survival without cognitive or physical impairments in older women. PMID- 20584835 TI - An extended midwifery support programme did not increase breast feeding at 6 months, compared with standard postnatal midwifery support. PMID- 20584836 TI - Compared to a general wellness programme, an 18-month exercise programme for older women improves bone mineral density and fall risk but has similar improvements in predicted coronary heart disease risk. PMID- 20584837 TI - Patient-to-nurse ratio in neonatal ICU associated with daily weight gain, but not other clinical outcomes in moderately preterm infants. PMID- 20584838 TI - High ambient temperature associated with increased mortality in nursing home residents. PMID- 20584839 TI - Daily multidisciplinary team rounds associated with reduced 30-day mortality in medical intensive care unit patients. PMID- 20584840 TI - Many factors can determine whether a woman continues to breastfeed: knowing that breastfeeding is good for the baby is important to mothers but breastfeeding in public continues to be a negative experience for some. PMID- 20584841 TI - Following bereavement, poor health is more likely in carers who perceived that their support from health services was insufficient or whose family member did not die in the carer's preferred place of death. PMID- 20584842 TI - Community-dwelling older adults with balance impairment show a moderate increase in fall risk, although further research is required to refine how balance measurement can be used in clinical practice. PMID- 20584843 TI - Over-the-counter weight loss with orlistat? AB - Orlistat first became available (as 120 mg capsules [Xenical]) around 10 years ago as a prescription-only treatment for obesity.1 Earlier this year, orlistat 60 mg capsules (alli - GlaxoSmithKline Consumer Healthcare) became available for sale without a prescription to the public in the European Union. Orlistat 60 mg is available in the UK as a Pharmacy (P) medicine and so can be purchased over the-counter (OTC) from pharmacies. OTC orlistat is promoted as a new weight loss aid, "boosting weight loss by 50%" when added to a reduced calorie, lower-fat diet. Here we review the place of OTC orlistat in tackling obesity. PMID- 20584845 TI - Misleading presentation of empyema. PMID- 20584844 TI - Review of haemophagocytic lymphohistiocytosis. AB - Haemophagocytic lymphohistiocytosis (HLH) describes a clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response. It may develop subsequent to a number of recognised genetic mutations or in association with infection, malignancy, autoinflammatory or metabolic conditions. Even with the published diagnostic criteria it can be difficult to make the diagnosis of HLH. Patients presenting acutely to the general paediatrician or paediatric intensivist with a clinical picture of likely sepsis, ie fever, laboratory evidence of inflammatory response, coagulopathy and thrombocytopaenia should be appropriately investigated and managed for sepsis, but the possible diagnosis of HLH should be borne in mind, particularly in the child who deteriorates despite maximal therapy. This review discusses current knowledge on the classification, diagnosis and management of primary and secondary HLH, and suggests a pathway of investigation for the paediatrician faced with a potential case. PMID- 20584846 TI - Case-control analysis of paternal age and trisomic anomalies. AB - OBJECTIVES: To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome. DESIGN: Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months. SETTING: Data from 22 EUROCAT congenital anomaly registers in 12 European countries. PARTICIPANTS: Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age >= 20 weeks and terminations after prenatal diagnosis of the anomaly. Data include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome. MAIN OUTCOME MEASURES: Odds ratio (OR) associated with a 10-year increase in paternal age for each anomaly was estimated using conditional logistic regression. Results were adjusted to take account of the estimated association of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23). RESULTS: The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26). CONCLUSIONS: There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age. The larger positive associations of Klinefelter and XYY syndromes with paternal age compared with Patau and Edwards syndromes are consistent with the greater percentage of these sex chromosome anomalies being of paternal origin. PMID- 20584847 TI - The TSH threshold in neonatal screening for congenital hypothyroidism: a variable solution. AB - An algorithm is described whereby the threshold for thyroid-stimulating hormone used in neonatal screening for congenital hypothyroidism is re-set for each run on the basis of the variation and values of measurements of certified samples. PMID- 20584848 TI - Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow. AB - BACKGROUND: The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. METHODS: All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. RESULTS: Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identified with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. SUMMARY: Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance. PMID- 20584849 TI - Clinical presentation of childhood neuroborreliosis; neurological examination may be normal. AB - OBJECTIVE: Neuroborreliosis has its highest incidence in children and the older people. Signs and symptoms are different between the different age groups. The aim of this study was to describe the clinical spectrum of neuroborreliosis in children. DESIGN: The Dutch Paediatric Surveillance system registered cases of childhood neuroborreliosis during 2 years. All Dutch paediatric hospitals took part in this surveillance. Criteria for reporting cases were strictly defined. RESULTS: 89 cases of neuroborreliosis were reported; in 66 cases diagnosis was confirmed. Facial weakness was one of the presenting symptoms in 47 cases (71%) and the only symptom in nine children (14%). The five complaints most frequently reported were: malaise, headache, fatigue, fever and neck pain. 52 children (79%) had one or more objective neurological signs at presentation, of which facial nerve palsy, other cranial nerve abnormalities and meningeal signs were most frequent. 14 patients (21%), however, had no neurological signs at physical examination. In these patients, the number of subjective complaints was higher, and the time interval to diagnosis was longer compared with those with objective neurological abnormalities. CONCLUSIONS: In this study, 79% of paediatric neuroborreliosis patients presented with neurological signs, most often facial nerve palsy. 21% presented in an atypical way without neurological signs. A thorough neurological examination is essential once neuroborreliosis is considered in children. Even in the absence of neurological signs, neuroborreliosis may be suspected in children with typical antecedents and multiple symptoms. Cerebrospinal fluid investigations are then required to confirm the diagnosis. PMID- 20584850 TI - Pain management in the paediatric population: the regulatory situation in Europe. AB - This study compared the availability and the licensing status of analgesic drugs marketed in three European countries (Italy, France and the UK) and evaluated the evidence on safety and efficacy in the paediatric population of the drugs reported in the European Medicines Evaluation (EMA) document "Assessment of Pediatric Needs: Pain" (2005). Ten of 17 drugs reported in the EMA document were marketed with a paediatric licence in all three countries but with wide differences concerning age groups. In all, 594 randomised controlled trials (RCTs) concerning the 17 drugs in the EMA list were found through biomedical literature databases. Bupivacaine was the drug with the most trials retrieved (171 RCTs, 29%); 32 (5%) RCTs concerned clonidine not licensed for pain control, and 51 (9%) concerned ketamine licensed for paediatric use only in the UK. Access to, and the rational use, of drugs to prevent or control pain and its functional consequences pose a considerable challenge. There is a pressing need for further research and clinical development in the assessment and management of pain in children. PMID- 20584851 TI - Drowning and sudden cardiac death. PMID- 20584852 TI - Drug approval processes in Australian Paediatric Hospitals. AB - OBJECTIVE: To describe and evaluate the decision-making processes for drug approval in Australian paediatric hospitals. DESIGN: Multicentre descriptive study involving face-to-face interviews of drug and therapeutics committee chairs and secretaries, review of committee documents and drug submissions for all Australian paediatric hospital drug and therapeutics committees over a 1-year period. SETTING: All eight paediatric hospitals in Australia. PARTICIPANTS: Eight committee chairs and seven secretaries or delegates. MAIN OUTCOME MEASURES: Total drug expenditure, number of formulary submissions, individual-patient use approvals and approval rates for each hospital from 1 July 2006 to 30 June 2007, stratified by therapeutic class. Qualitative description of the approval processes. RESULTS: Total drug expenditure varied from $A1.7 million (US$1.5 million) to $A11.1 million (US$9.8 million) per hospital. The number of formulary submissions also varied, from 7 to 21, but approval rate was high (76%-100%) and not significantly different among hospitals (p=0.17). Several committees approved identical submissions for five drugs. The number of individual-patient use applications varied considerably, ranging from 10 to 456 per hospital. Where estimable, individual-patient use approval was 76%-100% and variable (p=0.03). Quality of evidence relating to safety and efficacy of drugs being considered was regarded as the most important factors influencing decision making, with the cost less important. Most committees had poor infrastructural support for approval processes. No committee formally included a pharmaco-economic evaluation. CONCLUSIONS: Most drug submissions in tertiary paediatric hospitals are approved; however, workload, drug expenditure and individual-patient use schemes vary considerably. Duplication of effort occurs, and few committees are resourced sufficiently given their terms of reference. PMID- 20584853 TI - Exercise echocardiography and the diagnosis of heart failure with a normal ejection fraction. PMID- 20584854 TI - Mechanical synchrony and survival in heart failure. PMID- 20584855 TI - Novel biochemical markers in suspected acute coronary syndrome: systematic review and critical appraisal. AB - CONTEXT: Early recognition of acute coronary syndrome (ACS) is essential. Cardiac troponins are not consistently elevated within the first hours after symptom onset. OBJECTIVE: Review current guidelines recommendations regarding biomarkers in the early assessment of ACS and review the evidence for using established and specific new diagnostic biomarkers. DATA SOURCES: MEDLINE and EMBASE. STUDY SELECTION: Articles on diagnostic accuracy of ACS biomarkers. DATA EXTRACTION: Relevance of clinical domain, adequacy of measures of clinical utility and outcome assessment. RESULTS: The 73 articles identified on early biochemical markers CK-MB, myoglobin, heart-type fatty acid binding protein (H-FABP), ischemia modified albumin (IMA), pregnancy-associated plasma protein A, glycogen phosphorylase isoenzyme BB and myeloid-related protein 8/14 often did not quantify clinical utility correctly. CONCLUSIONS: IMA and H-FABP seem to be promising biomarkers in the early assessment of ACS. There is an urgent need for adequately designed diagnostic studies of (novel) ACS markers against contemporary troponin assays. PMID- 20584856 TI - Translational promise of the apelin--APJ system. AB - Apelin, the endogenous ligand for the G-protein-coupled APJ receptor, is emerging as a key hormone in cardiovascular homoeostasis. It is expressed in a diverse range of tissues with particular preponderance for the cardiovascular system, being found in both the heart and vasculature. Apelin is the most potent in vitro inotrope yet identified and causes endothelium- and nitric oxide-dependent vasodilatation. It also appears to have a role in lipid and glucose metabolism as well as fluid homoeostasis. One of the key emerging features of the apelin--APJ system is its interaction with the renin-angiotensin system with the respective receptors sharing marked sequence homology, forming heterodimers, and mediating opposing physiological actions. To date, both preclinical and limited clinical studies suggest that the apelin--APJ system may have an important role in the pathogenesis of heart failure. Although the apelin--APJ system is downregulated, the inotropic actions of apelin persist and are enhanced in failing hearts without inducing ventricular hypertrophy. In combination with its interaction with the renin-angiotensin system, APJ agonism may provide a new therapeutic target in the treatment of acute and chronic heart failure. In this review, we highlight key aspects of the apelin--APJ system in health and disease, and consider its translational and therapeutic potential. The diverse actions of the apelin--APJ system have implications for understanding the pathophysiology of, and development of treatments for, several major cardiovascular diseases. PMID- 20584857 TI - Reduced left atrial function on exercise in patients with heart failure and normal ejection fraction. AB - AIMS: The cardinal symptom of heart failure with a normal ejection fraction (HFNEF) is exertional dyspnoea. The authors hypothesised that failure of left atrial (LA) compensatory mechanism particularly on exercise contributes to the genesis of symptoms in HFNEF patients. METHODS AND RESULTS: Fifty HFNEF patients, 15 asymptomatic hypertensive subjects and 30 healthy controls underwent rest and submaximal exercise echocardiography. Rest and exercise systolic, early diastolic and late diastolic (Am) mitral annular velocities were assessed using colour tissue Doppler echocardiography. Left atrial functional reserve index was calculated. Am at rest was comparable between all three groups, but exercise Am was significantly lower in HFNEF compared with hypertensive subjects and healthy controls resulting in a lower LA functional reserve index (0.84 (1.34) vs 2.39 (1.27) and 1.81 (1.39), p<0.001). LA volume index was significantly higher in HFNEF patients (30.4 (9.2) vs 27.9 (6.3) and 23.2 (7.1) ml/m(2), p=0.002). There was a significant correlation between Am on exercise with peak VO(2) max (r=0.514, p<0.001) and E/Em on exercise (r=-0.547, p<0.001). Area under the receiver operating characteristic for Am on exercise was 0.768 (95% CI=0.660 to 0.877). CONCLUSION: HFNEF patients have reduced LA function on exercise in addition to left ventricular systolic and diastolic dysfunctions. Reduced LA function probably contributes significantly to exercise intolerance and breathlessness in HFNEF patients. PMID- 20584858 TI - Monocoronary system with malignant course of the LAD. PMID- 20584859 TI - Cardiac imaging in the patient with chest pain: echocardiography. PMID- 20584860 TI - Use of drug eluting stents in ST segment elevation myocardial infarction. PMID- 20584861 TI - Comparing exposure zones by different exposure metrics using statistical parameters: contrast and precision. AB - Recently, the appropriateness of using the 'mass concentration' metric for ultrafine particles has been questioned and surface area (SA) or number concentration metrics has been proposed as alternatives. To assess the abilities of various exposure metrics to distinguish between different exposure zones in workplaces with nanoparticle aerosols, exposure concentrations were measured in preassigned 'high-' and 'low-'exposure zones in a restaurant, an aluminum die casting factory, and a diesel engine laboratory using SA, number, and mass concentration metrics. Predetermined exposure classifications were compared by each metric using statistical parameters and concentration ratios that were calculated from the different exposure concentrations. In the restaurant, SA and fine particle number concentrations showed significant differences between the high- and low-exposure zones and they had higher contrast (the ratio of between zone variance to the sum of the between-zone and within-zone variances) than mass concentrations. Mass concentrations did not show significant differences. In the die cast facility, concentrations of all metrics were significantly greater in the high zone than in the low zone. SA and fine particle number concentrations showed larger concentration ratios between the high and low zones and higher contrast than mass concentrations. None of the metrics were significantly different between the high- and low-exposure zones in the diesel engine laboratory. The SA and fine particle number concentrations appeared to be better at differentiating exposure zones and finding the particle generation sources in workplaces generating nanoparticles. Because the choice of an exposure metric has significant implications for epidemiologic studies and industrial hygiene practice, a multimetric sampling approach is recommended for nanoparticle exposure assessment. PMID- 20584862 TI - Simple respiratory protection--evaluation of the filtration performance of cloth masks and common fabric materials against 20-1000 nm size particles. AB - A shortage of disposable filtering facepiece respirators can be expected during a pandemic respiratory infection such as influenza A. Some individuals may want to use common fabric materials for respiratory protection because of shortage or affordability reasons. To address the filtration performance of common fabric materials against nano-size particles including viruses, five major categories of fabric materials including sweatshirts, T-shirts, towels, scarves, and cloth masks were tested for polydisperse and monodisperse aerosols (20-1000 nm) at two different face velocities (5.5 and 16.5 cm s-1) and compared with the penetration levels for N95 respirator filter media. The results showed that cloth masks and other fabric materials tested in the study had 40-90% instantaneous penetration levels against polydisperse NaCl aerosols employed in the National Institute for Occupational Safety and Health particulate respirator test protocol at 5.5 cm s 1. Similarly, varying levels of penetrations (9-98%) were obtained for different size monodisperse NaCl aerosol particles in the 20-1000 nm range. The penetration levels of these fabric materials against both polydisperse and monodisperse aerosols were much higher than the penetrations for the control N95 respirator filter media. At 16.5 cm s-1 face velocity, monodisperse aerosol penetrations slightly increased, while polydisperse aerosol penetrations showed no significant effect except one fabric mask with an increase. Results obtained in the study show that common fabric materials may provide marginal protection against nanoparticles including those in the size ranges of virus-containing particles in exhaled breath. PMID- 20584863 TI - Temporary threshold shifts at 1500 and 2000 Hz induced by loud voice signals communicated through earphones in the pinball industry. AB - To assess the risk of hearing loss among workers using earphones as communication devices at noisy worksites, we compared temporary threshold shifts (TTS) between ears on which workers wore earphones and ears on which no earphones were worn. We measured ambient noise and personal noise exposure as well as noise generated by and passed through earphones by applying frequency analysis at three pinball facilities during their hours of actual operation. We assessed hearing levels before and after a work shift (prework and postwork) of 54 workers by pure tone audiometry at six frequencies. The time-weighted averages for ambient noise and personal noise exposure exceeded 85 dB(A) and 90 dB(A), respectively. Overall sound pressure levels generated by and passing through earphones reached 109 dB(A). The one-third octave band spectrum of the earphone noise during the shift exceeded 90 dB(SPL) in the range of 315-2000 Hz. The number of ears demonstrating a TTS, defined as a shift of 10 dB or more in postwork over prework hearing thresholds, was significantly greater at 1500 and 2000 Hz among ears with earphones (P < 0.05 and P < 0.01, respectively) compared to those without. The reverse was observed at 4000 Hz for ears without earphones (P < 0.01). Workers wearing earphones or headsets as communication devices in noisy environments are exposed to high risk of hearing loss, particularly at the frequencies of 1500 and 2000 Hz. Ideally, hearing conservation programs for such workers should account for potential hearing losses at frequencies of 2000 Hz or lower frequencies induced by amplified voice signals. PMID- 20584864 TI - Rehabilitation in practice: neurogenic lower urinary tract dysfunction and its management. AB - This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'the trainee consistent demonstrates a knowledge of the pathophysiology of various specific impairments including bladder dysfunction' and 'management approaches for specific impairments including bladder dysfunction'. The lower urinary tract (bladder and urethra) has two roles: storage of urine and emptying at appropriate times. The optimal and coordinated activity of the lower urinary tract is subject to a complex neural control which involves all levels of the nervous system, from cortex to peripheral innervation. The complexity of the neural control of lower urinary tract explains the high prevalence of urinary disturbances in neurologic disease. Information obtained from history taking and supplemented by use of a bladder diary forms the cornerstone of evaluation. Ultrasonography is used to assess the degree of incomplete bladder emptying, and for assessing the upper tracts. Urodynamic tests, with or without simultaneous fluoroscopic monitoring, assess detrusor and bladder outlet function and give fundamental information about detrusor pressure and thus the risk factor for upper tract damage. Impaired emptying is most often managed by clean intermittent self-catheterization and this should be initiated if the post-void residual urine is greater than 100 mL or exceeds one third of bladder capacity, or rarely if spontaneous voiding is dangerous due to high detrusor pressure. Storage symptoms are most often managed using antimuscarinic medications. Other options include desmopressin to reduce urine output or intra detrusor injection of botulinum toxin type A to reduce detrusor overactivity. Understanding of the underlying mechanism of lower urinary tract dysfunction is crucial for effective management. PMID- 20584867 TI - Letter to the editor: Effects of electro-acupuncture on patients with schizophrenia. PMID- 20584868 TI - Lipoprotein(a) accelerates atherosclerosis in uremic mice. AB - Uremic patients have increased plasma lipoprotein(a) [Lp(a)] levels and elevated risk of cardiovascular disease. Lp(a) is a subfraction of LDL, where apolipoprotein(a) [apo(a)] is disulfide bound to apolipoprotein B-100 (apoB). Lp(a) binds oxidized phospholipids (OxPL), and uremia increases lipoprotein associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n = 19), human apoB 100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo(a)-Tg and WT mice. Uremia did not result in increased plasma apo(a) or Lp(a). Mean atherosclerotic plaque area in the aortic root was increased 1.8-fold in apo(a)-Tg (P = 0.025) and 3.3-fold (P = 0.0001) in Lp(a)-Tg mice compared with WT mice. Plasma OxPL, as detected with the E06 antibody, was associated with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia. PMID- 20584869 TI - Negative intratracheal pressure produced by esophageal detector devices causes tracheal wall collapse in a porcine cardiac arrest model. AB - BACKGROUND: Esophageal detector devices (EDDs) impose negative pressure on the trachea or esophagus to verify endotracheal tube (ETT) position. In cardiac arrest, the smooth muscle of the lower esophageal sphincter relaxes in a time dependent and irreversible manner. If relaxation also occurs in the muscular posterior tracheal wall, it could predispose tracheal invagination or collapse with negative pressure, potentially yielding false-negative (tracheal ETT, EDD indicates esophagus) results. We compared 3 different EDDs in their ability to correctly discriminate tracheal and esophageal intubation. METHODS: ETTs were placed into the trachea and esophagus of 5 domestic swine, and bronchoscopy was used to visualize the trachea while 3 EDDs were tested. Tracheal wall activity was observed before and after induced cardiac arrest. Tracheal ETTs were aspirated with increasing negative force and pressures at initial wall movement and >50% tracheal lumen obliteration were recorded. Measurements were repeated at 4, 8, and 12 minutes postarrest and pressures at tracheal wall collapse pre- and postarrest were determined. EDDs were also tested on esophageal ETTs prearrest and at 6 and 10 minutes postarrest. RESULTS: In a closed system, each EDD generated more than -100 cm H(2)O pressure. Average prearrest pressure at tracheal collapse was -112 cm H(2)O. Average postarrest collapse pressures were 68, -66, and -54 cm H(2)O at 4, 8, and 12 minutes postarrest. One EDD consistently gave equivocal results; the remaining 2 gave accurate results in all subjects. Most observed movement was insufficient to cause device failure although tracheal wall movement was noted in all postarrest EDD trials. Esophageal intubation was correctly determined at all times pre- and postarrest. CONCLUSION: These findings describe a mechanism for false-negative results from decreased posterior tracheal wall tone during cardiac arrest. Further studies are required to elucidate factors contributing to its occurrence and impact on EDD use. PMID- 20584870 TI - Echo rounds: intramural left coronary artery. PMID- 20584871 TI - Brief report: the long-term outcome of mandibular nerve block with alcohol for the treatment of trigeminal neuralgia. AB - Ninety-eight patients received 160 mandibular nerve (V3) blocks with alcohol for the treatment of trigeminal neuralgia in this prospective study. According to the Kaplan-Meier analysis, the probabilities of remaining pain free for 1, 2, 3, and 7 years after the procedures were 90.4%, 69%, 53.5%, and 33%, respectively. There was no significant difference in the probability of pain-free duration and complications between patients with repeat versus single V3 block with alcohol. We conclude that single and repeat V3 alcohol block for trigeminal neuralgia can provide long-lasting pain relief. PMID- 20584872 TI - Transcutaneous carbon dioxide monitoring accurately predicts arterial carbon dioxide partial pressure in patients undergoing prolonged laparoscopic surgery. AB - BACKGROUND: There may be large differences between measurements of end-tidal carbon dioxide partial pressure (Petco(2)) and arterial carbon dioxide partial pressure (Paco(2)) during laparoscopic surgeries. Transcutaneous carbon dioxide (Ptcco(2)) monitoring can be used to noninvasively and continuously estimate Paco(2). In the present study we evaluated the accuracy of Ptcco(2) monitoring in predicting the Paco(2) during laparoscopic surgeries with prolonged pneumoperitoneum. METHODS: Sixteen patients who underwent laparoscopic radical gastrectomy or radical proctectomy under general anesthesia were included in the study. Their Paco(2), Petco(2), and Ptcco(2) values were measured at 3 time points before and after pneumoperitoneum. Agreement among measures was assessed by the Bland-Altman method. RESULTS: Forty-eight sample sets were obtained. The average Paco(2)- Ptcco(2) difference was -0.9 + or - 6.4 mm Hg (mean + or - 2 SD). The average Paco(2) - Petco(2) difference was 7.5 + or - 7.0 mm Hg (mean + or - 2 SD). Paco(2) - Ptcco(2) was less than or equal to + or -5 mm Hg for 88% of the samples. Paco(2) - Petco(2) was less than or equal to + or -5 mm Hg for 17% of the samples (P < 0.05). CONCLUSIONS: While undergoing long-term pneumoperitoneum laparoscopic surgery, Ptcco(2) monitoring is more accurate than is PETCO(2) monitoring in predicting the patients' Paco(2). PMID- 20584873 TI - Analysis of operating room allocations to optimize scheduling of specialty rotations for anesthesia trainees. AB - INTRODUCTION: Because specialty workloads and corresponding operating room (OR) allocations vary among days of the week, anesthesia residents and student nurse anesthetists are sometimes assigned to cases off rotation (e.g., scheduled for cardiac surgery but assigned to urology for the day). We describe a method to create hybrid rotations of two specialties (e.g., cardiac and vascular surgery), thereby reducing the numbers of days that trainees are "pulled" from their scheduled rotations. METHODS: Raw data were the number of hours of OR time used by each surgical specialty on each workday for the preceding 9 months. These OR workloads were converted to the number of ORs to be allocated to each specialty for each day of the week on the basis of maximization of the efficiency of use of OR time. We considered all potential hybrid rotations of pairwise combinations of specialties to which trainees could be assigned. Integer linear programming was used to calculate the maximum number of trainees who could be scheduled to hybrid rotations and receive daily assignments matching those rotations. RESULTS: Validity of the results was shown by using data from a small facility for which the optimal solution could be discerned by inspection. Validity (appropriateness) of the constraints was demonstrated by the exclusion of each constraint, resulting in answers that are obviously incorrect. Novelty and usefulness of the method was evidenced by its choosing from among hundreds of thousands of potential combinations of specialties and its identifying appropriate assignments that were substantively different from current rotations. CONCLUSIONS: We developed a methodology to determine rotations consisting of combinations of specialties to be paired for purposes of trainee scheduling to reduce the incidence of daily assignments off rotation. Practically, with this method, anesthesia residents and student nurse anesthetists can be assigned cases within their scheduled rotations as often as possible. PMID- 20584874 TI - Brief report: the effects of the menstrual cycle on the hemodynamic response to laryngoscopy and tracheal intubation. AB - We designed this study to determine the effect of the menstrual cycle on the hemodynamic response to tracheal intubation (TI). Sixty-two ASA I women who were either in the follicular phase (group F, n = 31) or luteal phase (group L, n = 31) of their menstrual cycle were included in the study. Patients received propofol and rocuronium for intubation. Hemodynamic variables were recorded before administration of the IV anesthetic, as well as after TI. Rate pressure products were calculated. Groups were similar in terms of demographic data. Rate pressure products values at the first minute after TI were significantly increased in group L than were those in group F (P < 0.001). We conclude that the phase of the menstrual cycle is an important factor in the hemodynamic response to TI. PMID- 20584875 TI - Aortic cross-clamping and reperfusion in pigs reduces microvascular oxygenation by altered systemic and regional blood flow distribution. AB - BACKGROUND: In this study, we tested the hypothesis that aortic cross-clamping (ACC) and reperfusion cause distributive alterations of oxygenation and perfusion in the microcirculation of the gut and kidneys despite normal systemic hemodynamics and oxygenation. METHODS: Fifteen anesthetized pigs were randomized between an ACC group (n = 10), undergoing 45 minutes of aortic clamping above the superior mesenteric artery, and a time-matched sham surgery control group (n = 5). Systemic, intestinal, and renal hemodynamics and oxygenation variables were monitored during 4 hours of reperfusion. Microvascular oxygen partial pressure (microPo(2)) was measured in the intestinal serosa and mucosa and the renal cortex, using the Pd-porphyrin phosphorescence technique. Intestinal luminal Pco(2) was determined by air tonometry and the serosal microvascular flow by orthogonal polarization spectral imaging. RESULTS: Organ blood flow and renal and intestinal microPo(2) decreased significantly during ACC, whereas the intestinal oxygen extraction and Pco(2) gap increased. The intestinal response to reperfusion after ACC was a sustained reactive hyperemia but no such effect was seen in the kidney. Despite a sustained high intestinal O(2) delivery, serosal microPo(2) (median [range], 49 mm Hg [41-67 mm Hg] versus 37 mm Hg [27-41 mm Hg]; P < 0.05 baseline versus 4 hours reperfusion) and the absolute number of perfused microvessels decreased along with an increased intestinal Pco(2) gap (17 mm Hg [10-19 mm Hg] versus 23 mm Hg [19-30 mm Hg]; P < 0.05). In contrast, the kidney showed a progressive O(2) delivery decrease accompanied by a decrease in renal cortex oxygenation (70 mm Hg [52-93 mm Hg] versus 57 mm Hg [33-64 mm Hg]; P < 0.05). CONCLUSION: Increased systemic and regional blood flow and oxygen supply after ACC does not ensure adequate regional blood flow and microcirculatory oxygenation in all organs. PMID- 20584876 TI - Case report: pudendal nerve injury after a sciatic nerve block by the posterior approach. AB - We report a pudendal nerve injury that developed after a posterior approach to the sciatic nerve. A classical Labat's posterior sciatic nerve block on the right side was performed using an insulated needle and a nerve stimulator set at an initial current of 2 mA, 2 Hz frequency, and 0.1 ms duration. Painful paresthesia radiating to the right side of the patient's penis and right leg was experienced shortly after needle insertion. The needle was immediately withdrawn and redirected laterally. Motor responses for the common peroneal and tibial components of the sciatic nerve were elicited at 0.48 mA in both cases and a 10 mL bolus of mepivacaine 1.5% was injected onto each component. The sciatic nerve block was combined with a femoral nerve block to facilitate a knee arthroscopy. The trauma resulted in erectile dysfunction and partial loss of penile sensation as well as evidence of injury to the sciatic nerve itself. Symptoms and clinical signs of pudendal nerve injury lasted 7 months. This is the first time that sexual dysfunction as a result of a unilateral pudendal nerve injury that occurred after a posterior sciatic nerve block has been reported. PMID- 20584877 TI - Pain management after elective hallux valgus surgery: a prospective randomized double-blind study comparing etoricoxib and tramadol. AB - BACKGROUND: Pain is a common complaint after day surgery, and there is still a controversy surrounding the use of selective cyclooxygenase-2 (COX-2) inhibitors. In the present prospective, randomized, double-blind study we compared pain management with a selective (COX-2) inhibitor (etoricoxib) with pain management using sustained-release tramadol after elective hallux valgus surgery. METHODS: One hundred ASA 1 to 2 female patients were randomized into 2 groups of 50 patients each; oral etoricoxib 120 mg x 1 x IV + 90 mg x 1 x day V-VII and oral tramadol sustained-release 100 mg x 2 x VII. Pain, pain relief, satisfaction with pain management, and need for rescue medication were evaluated during the first 7 postoperative days. A computed tomography scan evaluating bone healing was performed 12 weeks after surgery. A clinical evaluation of outcome (healing, mobility, and patient-assessed satisfaction) was performed 16 weeks after surgery. RESULTS: Two patients withdrew before discharge from the hospital. Ninety-eight patients, 81 ASA 1 and 17 ASA 2 (82 nonsmokers and 14 smokers), mean age 49 years (19-65), weight 64 (47-83) kg, and height 167 (154-183) cm were evaluated. Overall pain was well managed, but the mean visual analog scale (VAS) was significantly lower among etoricoxib patients evaluated during the entire 7 day period studied (12.5 + or - 8.3 vs. 17.3 + or - 11, P < 0.05). patient's grading of pain relief (92 + or - 12 vs. 85 + or - 15, P < 0.05) and satisfaction with pain medication (47/49 vs. 39/49, P < 0.05) was higher among etoricoxib patients. Patients receiving tramadol reported significantly more side effects. Six patients, all in the tramadol group, discontinued the study because of side effects (P < 0.05). At 14-day follow-up 1 patient in the etoricoxib group and 5 patients in the tramadol group exhibited minor irritation in the wound area. The 12-week computed tomography scan showed good healing in 82 patients, 43 in the etoricoxib group, and 39 in the tramadol group. The study found ongoing healing in 11 patients, 4 in the etoricoxib group and 7 in the tramadol group. The 16 week patient-assessed Health Profile Quality of life revealed high patient satisfaction overall; 47 patients in each study group rated the outcome as satisfactory and the mean change in the patient-assessed quality of life VAS score was 6.2 and 2.6 for the etoricoxib and tramadol groups, respectively. Clinical follow-up at 16 weeks showed high functionality and no signs or symptoms of improper healing in any patient. CONCLUSION: Etoricoxib was found to be more effective and associated with fewer side effects in comparison with tramadol sustained release as a component of multimodel analgesia after elective hallux valgus surgery. There were no signs of impaired wound or bone healing associated with the use of etoricoxib. PMID- 20584878 TI - An analysis of household waste management policy using system dynamics modelling. AB - This paper analyses the Flemish household waste management policy. Based on historical data from the period 1991-2006, literature reviews and interviews, both mathematical and descriptive relationships are derived that describe Flemish waste collection, reuse, recycling and disposal behaviour. This provides insights into how gross domestic product (GDP), population and selective collection behaviour have influenced household waste production and collection over time. These relationships are used to model the dynamic relationships underlying household waste management in Flanders by using a system dynamics (SD) modelling approach. Where most SD models in literature are conceptual and descriptive, in the present study a real-life case with both correlational and descriptive relationships was modelled for Flanders, a European region with an outstanding waste management track record. This model was used to evaluate the current Flemish household waste management policy based on the principles of the waste hierarchy, also referred as the Lansink ranking. The results show that Flemish household waste targets up to 2015 can be achieved by the current waste policy measures. It also shows the sensitivity of some key policy parameters such as prevention and reuse. Given the general nature of the model and its limited data requirements, the authors believe that the approach implemented in this model can also assist waste policy makers in other regions or countries to meet their policy targets by simulating the effect of their current and potential household waste policy measures. PMID- 20584879 TI - Rosiglitazone and the case for safety over certainty. PMID- 20584880 TI - Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. AB - CONTEXT: Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes. OBJECTIVE: To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States. DESIGN, SETTING, AND PATIENTS: Nationwide, observational, retrospective, inception cohort of 227,571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation. MAIN OUTCOME MEASURES: Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference. RESULTS: A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12 1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year. CONCLUSION: Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older. PMID- 20584881 TI - Oviductal secretions: will they be key factors for the future ARTs? AB - A variety of evolutionary processes has led to the development of different organs to ensure that internal fertilization occur successfully. Fallopian tubes are a particularly interesting example of such organs. Some of the key events during fertilization and early embryo development occur in the oviduct. Knowledge of the different components described in the oviduct is extensive. Oviductal components include hormones, growth factors and their receptors that have important roles in the physiology of the oviduct and embryo development. Other oviductal factors protect the gamete and the embryos against oxidative stress and pathogens. Different proteins and enzymes are present in the oviductal fluid and have the ability to interact with the oocyte and the sperm before the fertilization occurs. Of special interest is the oviduct-specific glycoprotein (OVGP1), a glycoprotein that is conserved in different mammals, and its association with the zona pellucida (ZP). Interaction of the oocyte with oviductal secretions leads us to emphasize the concept of 'ZP maturation' within the oviduct. The ZP changes produced in the oviduct result in an increased efficiency of the in vitro fertilization technique in some animal models, contributing in particular to the control of polyspermy and suggesting that a similar role could be played by oviductal factors in human beings. Finally, attention should be given to the presence in the oviductal fluid of several embryotrophic factors and their importance in relation to the in vivo versus in vitro developmental ability of the embryos. PMID- 20584882 TI - The Plasmodium eukaryotic initiation factor-2alpha kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. AB - Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2alpha (eIF2alpha) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2alpha phosphatase removes the PO4 from eIF2alpha-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2alpha is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells. PMID- 20584883 TI - Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics. AB - The sphingosine 1-phosphate receptor 1 (S1P(1)) promotes lymphocyte egress from lymphoid organs. Previous work showed that agonist-induced internalization of this G protein-coupled receptor correlates with inhibition of lymphocyte egress and results in lymphopenia. However, it is unclear if S1P(1) internalization is necessary for this effect. We characterize a knockin mouse (S1p1r(S5A/S5A)) in which the C-terminal serine-rich S1P(1) motif, which is important for S1P(1) internalization but dispensable for S1P(1) signaling, is mutated. T cells expressing the mutant S1P(1) showed delayed S1P(1) internalization and defective desensitization after agonist stimulation. Mutant mice exhibited significantly delayed lymphopenia after S1P(1) agonist administration or disruption of the vascular S1P gradient. Adoptive transfer experiments demonstrated that mutant S1P(1) expression in lymphocytes, rather than endothelial cells, facilitated this delay in lymphopenia. Thus, cell-surface residency of S1P(1) on T cells is a primary determinant of lymphocyte egress kinetics in vivo. PMID- 20584885 TI - Paul F. Cranefield Award to Merritt C. Maduke. PMID- 20584884 TI - Identification of an immediate Foxp3(-) precursor to Foxp3(+) regulatory T cells in peripheral lymphoid organs of nonmanipulated mice. AB - CD4(+)CD25(+) regulatory T cells (T reg cells) expressing the transcription factor Foxp3 can be induced from peripheral T cell receptor (TCR) transgenic CD4(+)CD25(-)Foxp3(-) T cells stimulated with noninflammatory dendritic cells presenting low amounts of agonist cognate antigen. However, limited evidence exists for extra-thymic T reg cell generation from non-TCR transgenic T cells in unmanipulated mice. We compared events early during agonist-driven generation of Foxp3(+) TCR transgenic T cells to polyclonal CD4(+) T cell populations in unmanipulated mice. We identified an interleukin-2- and phosphatidylinositol-3 kinase-dependent precommitted Foxp3(-) precursor to Foxp3(+) T reg cells in peripheral lymphoid organs. Transforming growth factor beta signaling played a minor role in the generation and subsequent differentiation of these T reg precursor cells. PMID- 20584886 TI - Emerging questions about the macromolecular machines of muscle. PMID- 20584887 TI - Looking for answers to EC coupling's persistent questions. PMID- 20584888 TI - The curious role of sarcomeric proteins in control of diverse processes in cardiac myocytes. PMID- 20584889 TI - Regulation of contraction in mammalian striated muscles--the plot thick-ens. PMID- 20584890 TI - Mechanisms of muscle weakness in muscular dystrophy. PMID- 20584891 TI - Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome. AB - Mutations in GJB2, which encodes Cx26, are one of the most common causes of inherited deafness in humans. More than 100 mutations have been identified scattered throughout the Cx26 protein, most of which cause nonsyndromic sensorineural deafness. In a subset of mutations, deafness is accompanied by hyperkeratotic skin disorders, which are typically severe and sometimes fatal. Many of these syndromic deafness mutations localize to the amino-terminal and first extracellular loop (E1) domains. Here, we examined two such mutations, A40V and G45E, which are positioned near the TM1/E1 boundary and are associated with keratitis ichthyosis deafness (KID) syndrome. Both of these mutants have been reported to form hemichannels that open aberrantly, leading to "leaky" cell membranes. Here, we quantified the Ca(2+) sensitivities and examined the biophysical properties of these mutants at macroscopic and single-channel levels. We find that A40V hemichannels show significantly impaired regulation by extracellular Ca(2+), increasing the likelihood of aberrant hemichannel opening as previously suggested. However, G45E hemichannels show only modest impairment in regulation by Ca(2+) and instead exhibit a substantial increase in permeability to Ca(2+). Using cysteine substitution and examination of accessibility to thiol-modifying reagents, we demonstrate that G45, but not A40, is a pore-lining residue. Both mutants function as cell-cell channels. The data suggest that G45E and A40V are hemichannel gain-of-function mutants that produce similar phenotypes, but by different underlying mechanisms. A40V produces leaky hemichannels, whereas G45E provides a route for excessive entry of Ca(2+). These aberrant properties, alone or in combination, can severely compromise cell integrity and lead to increased cell death. PMID- 20584892 TI - Fast and slow voltage sensor rearrangements during activation gating in Kv1.2 channels detected using tetramethylrhodamine fluorescence. AB - The Kv1.2 channel, with its high resolution crystal structure, provides an ideal model for investigating conformational changes associated with channel gating, and fluorescent probes attached at the extracellular end of S4 are a powerful way to gain a more complete understanding of the voltage-dependent activity of these dynamic proteins. Tetramethylrhodamine-5-maleimide (TMRM) attached at A291C reports two distinct rearrangements of the voltage sensor domains, and a comparative fluorescence scan of the S4 and S3-S4 linker residues in Shaker and Kv1.2 shows important differences in their emission at other homologous residues. Kv1.2 shows a rapid decrease in A291C emission with a time constant of 1.5 +/- 0.1 ms at 60 mV (n = 11) that correlates with gating currents and reports on translocation of the S4 and S3-S4 linker. However, unlike any Kv channel studied to date, this fast component is dwarfed by a larger, slower quenching of TMRM emission during depolarizations between -120 and -50 mV (tau = 21.4 +/- 2.1 ms at 60 mV, V(1/2) of -73.9 +/- 1.4 mV) that is not seen in either Shaker or Kv1.5 and that comprises >60% of the total signal at all activating potentials. The slow fluorescence relaxes after repolarization in a voltage-dependent manner that matches the time course of Kv1.2 ionic current deactivation. Fluorophores placed directly in S1 and S2 at I187 and T219 recapitulate the time course and voltage dependence of slow quenching. The slow component is lost when the extracellular S1-S2 linker of Kv1.2 is replaced with that of Kv1.5 or Shaker, suggesting that it arises from a continuous internal rearrangement within the voltage sensor, initiated at negative potentials but prevalent throughout the activation process, and which must be reversed for the channel to close. PMID- 20584893 TI - The codon specificity of eubacterial release factors is determined by the sequence and size of the recognition loop. AB - The two codon-specific eubacterial release factors (RF1: UAA/UAG and RF2: UAA/UGA) have specific tripeptide motifs (PXT/SPF) within an exposed recognition loop shown in recent structures to interact with stop codons during protein synthesis termination. The motifs have been inferred to be critical for codon specificity, but this study shows that they are insufficient to determine specificity alone. Swapping the motifs or the entire loop between factors resulted in a loss of codon recognition rather than a switch of codon specificity. From a study of chimeric eubacterial RF1/RF2 recognition loops and an atypical shorter variant in Caenorhabditis elegans mitochondrial RF1 that lacks the classical tripeptide motif PXT, key determinants throughout the whole loop have been defined. It reveals that more than one configuration of the recognition loop based on specific sequence and size can achieve the same desired codon specificity. This study has provided unexpected insight into why a combination of the two factors is necessary in eubacteria to exclude recognition of UGG as stop. PMID- 20584895 TI - Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons. AB - microRNAs (miRNAs) constitute a novel class of small, noncoding RNAs that act as negative post-transcriptional regulators of gene expression. Although the nervous system is a prominent site of miRNA expression, little is known about the spatial expression profiles of miRNAs in neurons. Here, we employed compartmentalized Campenot cell culture chambers to obtain a pure axonal RNA fraction of superior cervical ganglia (SCG) neurons, and determined the miRNA expression levels in these subcellular structural domains by microarray analysis and by real-time reverse-transcription polymerase chain reaction. The data revealed stable expression of a number of mature miRNAs that were enriched in the axons and presynaptic nerve terminals. Among the 130 miRNAs identified in the axon, miR 15b, miR-16, miR-204, and miR-221 were found to be highly abundant in distal axons as compared with the cell bodies of primary sympathetic neurons. Moreover, a number of miRNAs encoded by a common primary transcript (pri-miRNA) were differentially expressed in the distal axons, suggesting that there is a differential subcellular transport of miRNAs derived from the same coding region of the genome. Taken together, the data provide an important resource for future studies on the regulation of axonal protein synthesis and the role played by miRNAs in the maintenance of axonal structure and function as well as neuronal growth and development. PMID- 20584894 TI - Heterogeneous nuclear ribonucleoproteins (hnRNPs) in cellular processes: Focus on hnRNP E1's multifunctional regulatory roles. AB - Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a family of RNA binding proteins. The complexity and diversity associated with the hnRNPs render them multifunctional, involved not only in processing heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs, but also acting as trans-factors in regulating gene expression. Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1), a subgroup of hnRNPs, is a KH-triple repeat containing RNA-binding protein. It is encoded by an intronless gene arising from hnRNP E2 through a retrotransposition event. hnRNP E1 is ubiquitously expressed and functions in regulating major steps of gene expression, including pre-mRNA processing, mRNA stability, and translation. Given its wide-ranging functions in the nucleus and cytoplasm and interaction with multiple proteins, we propose a post-transcriptional regulon model that explains hnRNP E1's widespread functional diversity. PMID- 20584896 TI - The HCV IRES pseudoknot positions the initiation codon on the 40S ribosomal subunit. AB - The hepatitis C virus (HCV) genomic RNA contains an internal ribosome entry site (IRES) in its 5' untranslated region, the structure of which is essential for viral protein translation. The IRES includes a predicted pseudoknot interaction near the AUG start codon, but the results of previous studies of its structure have been conflicting. Using mutational analysis coupled with activity and functional assays, we verified the importance of pseudoknot base pairings for IRES-mediated translation and, using 35 mutants, conducted a comprehensive study of the structural tolerance and functional contributions of the pseudoknot. Ribosomal toeprinting experiments show that the entirety of the pseudoknot element positions the initiation codon in the mRNA binding cleft of the 40S ribosomal subunit. Optimal spacing between the pseudoknot and the start site AUG resembles that between the Shine-Dalgarno sequence and the initiation codon in bacterial mRNAs. Finally, we validated the HCV IRES pseudoknot as a potential drug target using antisense 2'-OMe oligonucleotides. PMID- 20584897 TI - Direct detection of RNA in vitro and in situ by target-primed RCA: The impact of E. coli RNase III on the detection efficiency of RNA sequences distanced far from the 3'-end. AB - We improved the target RNA-primed RCA technique for direct detection and analysis of RNA in vitro and in situ. Previously we showed that the 3' --> 5' single stranded RNA exonucleolytic activity of Phi29 DNA polymerase converts the target RNA into a primer and uses it for RCA initiation. However, in some cases, the single-stranded RNA exoribonucleolytic activity of the polymerase is hindered by strong double-stranded structures at the 3'-end of target RNAs. We demonstrate that in such hampered cases, the double-stranded RNA-specific Escherichia coli RNase III efficiently assists Phi29 DNA polymerase in converting the target RNA into a primer. These observations extend the target RNA-primed RCA possibilities to test RNA sequences distanced far from the 3'-end and customize this technique for the inner RNA sequence analysis. PMID- 20584898 TI - Monitoring viral RNA in infected cells with LNA flow-FISH. AB - We previously showed the feasibility of using locked nucleic acid (LNA) for flow cytometric-fluorescence in situ hybridization (LNA flow-FISH) detection of a target cellular mRNA. Here we demonstrate how the method can be used to monitor viral RNA in infected cells. We compared the results of the LNA flow-FISH with other methods of quantifying virus replication, including the use of an enhanced green fluorescent protein (EGFP) viral construct and quantitative reverse transcription polymerase chain reaction. We found that an LNA probe complementary to Sindbis virus RNA is able to track the increase in viral RNA over time in early infection. In addition, this method is comparable to the EGFP construct in sensitivity, with both peaking around 3 h and at the same level of infected cells. Finally, we observed that the LNA flow-FISH method responds to the decrease in levels of viral RNA caused by antiviral medication. This technique represents a straightforward way to monitor viral infection in cells and is easily applicable to any virus. PMID- 20584899 TI - Transcriptome and targetome analysis in MIR155 expressing cells using RNA-seq. AB - Previous studies have demonstrated the utility of microarray expression analysis to identify potential microRNA targets. Nevertheless, technical limitations intrinsic to this platform constrain its ability to fully exploit the potential of assessing transcript level changes to explore microRNA targetomes. High throughput multiplexed Illumina-based next-generation sequencing (NGS) provides a digital readout of absolute transcript levels and imparts a higher level of accuracy and dynamic range than microarray platforms. We used Illumina NGS to analyze transcriptome changes induced by the human microRNA MIR155. This analysis resulted in a larger inferred targetome than similar studies carried out using microarray platforms. A comparison with 3' UTR reporter data demonstrated general concordance between NGS and corresponding 3' UTR reporter results. Nonharmonious results were investigated more deeply using transcript structure information assembled from the NGS data. This analysis revealed that transcript structure plays a substantial role in mitigated targeting and in frank targeting failures. With its high level of accuracy, its broad dynamic range, its utility in assessing transcript structure, and its capacity to accurately interrogate global direct and indirect transcriptome changes, NGS is a useful tool for investigating the biology and mechanisms of action of microRNAs. PMID- 20584900 TI - A small ubiquitin-related modifier-interacting motif functions as the transcriptional activation domain of Kruppel-like factor 4. AB - The zinc finger transcription factor, Kruppel-like factor 4 (KLF4), regulates numerous biological processes, including proliferation, differentiation, and embryonic stem cell self-renewal. Although the DNA sequence to which KLF4 binds is established, the mechanism by which KLF4 controls transcription is not well defined. Small ubiquitin-related modifier (SUMO) is an important regulator of transcription. Here we show that KLF4 is both SUMOylated at a single lysine residue and physically interacts with SUMO-1 in a region that matches an acidic and hydrophobic residue-rich SUMO-interacting motif (SIM) consensus. The SIM in KLF4 is required for transactivation of target promoters in a SUMO-1-dependent manner. Mutation of either the acidic or hydrophobic residues in the SIM significantly impairs the ability of KLF4 to interact with SUMO-1, activate transcription, and inhibit cell proliferation. Our study provides direct evidence that SIM in KLF4 functions as a transcriptional activation domain. A survey of transcription factor sequences reveals that established transactivation domains of many transcription factors contain sequences highly related to SIM. These results, therefore, illustrate a novel mechanism by which SUMO interaction modulates the activity of transcription factors. PMID- 20584901 TI - Identification of eukaryotic and prokaryotic methylthiotransferase for biosynthesis of 2-methylthio-N6-threonylcarbamoyladenosine in tRNA. AB - Bacterial and eukaryotic transfer RNAs have been shown to contain hypermodified adenosine, 2-methylthio-N(6)-threonylcarbamoyladenosine, at position 37 (A(37)) adjacent to the 3'-end of the anticodon, which is essential for efficient and highly accurate protein translation by the ribosome. Using a combination of bioinformatic sequence analysis and in vivo assay coupled to HPLC/MS technique, we have identified, from distinct sequence signatures, two methylthiotransferase (MTTase) subfamilies, designated as MtaB in bacterial cells and e-MtaB in eukaryotic and archaeal cells. Both subfamilies are responsible for the transformation of N(6)-threonylcarbamoyladenosine into 2-methylthio-N(6) threonylcarbamoyladenosine. Recently, a variant within the human CDKAL1 gene belonging to the e-MtaB subfamily was shown to predispose for type 2 diabetes. CDKAL1 is thus the first eukaryotic MTTase identified so far. Using purified preparations of Bacillus subtilis MtaB (YqeV), a CDKAL1 bacterial homolog, we demonstrate that YqeV/CDKAL1 enzymes, as the previously studied MTTases MiaB and RimO, contain two [4Fe-4S] clusters. This work lays the foundation for elucidating the function of CDKAL1. PMID- 20584902 TI - Structure of pleiotrophin- and hepatocyte growth factor-binding sulfated hexasaccharide determined by biochemical and computational approaches. AB - Endogenous pleiotrophin and hepatocyte growth factor (HGF) mediate the neurite outgrowth-promoting activity of chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains isolated from embryonic pig brain. CS/DS hybrid chains isolated from shark skin have a different disaccharide composition, but also display these activities. In this study, pleiotrophin- and HGF-binding domains in shark skin CS/DS were investigated. A high affinity CS/DS fraction was isolated using a pleiotrophin-immobilized column. It showed marked neurite outgrowth-promoting activity and strong inhibitory activity against the binding of pleiotrophin to immobilized CS/DS chains from embryonic pig brain. The inhibitory activity was abolished by chondroitinase ABC or B, and partially reduced by chondroitinase AC I. A pentasulfated hexasaccharide with a novel structure was isolated from the chondroitinase AC-I digest using pleiotrophin affinity and anion exchange chromatographies. It displayed a potent inhibitory effect on the binding of HGF to immobilized shark skin CS/DS chains, suggesting that the pleiotrophin- and HGF binding domains at least partially overlap in the CS/DS chains involved in the neuritogenic activity. Computational chemistry using molecular modeling and calculations of the electrostatic potential of the hexasaccharide and two pleiotrophin-binding octasaccharides previously isolated from CS/DS hybrid chains of embryonic pig brain identified an electronegative zone potentially involved in the molecular recognition of the oligosaccharides by pleiotrophin. Homology modeling of pleiotrophin based on a related midkine protein structure predicted the binding pocket of pleiotrophin for the oligosaccharides and provided new insights into the molecular mechanism of the interactions between the oligosaccharides and pleiotrophin. PMID- 20584903 TI - Bcl-2 and Bax interact via the BH1-3 groove-BH3 motif interface and a novel interface involving the BH4 motif. AB - The interaction of Bcl-2 family proteins at the mitochondrial outer membrane controls membrane permeability and thereby the apoptotic program. The anti apoptotic protein Bcl-2 binds to the pro-apoptotic protein Bax to prevent Bax homo-oligomerization required for membrane permeabilization. Here, we used site specific photocross-linking to map the surfaces of Bax and Bcl-2 that interact in the hetero-complex formed in a Triton X-100 micelle as a membrane surrogate. Heterodimer-specific photoadducts were detected from multiple sites in Bax and Bcl-2. Many of the interaction sites are located in the Bcl-2 homology 3 (BH3) region of Bax and the BH1-3 groove of Bcl-2 that likely form the BH3-BH1-3 groove interface. However, other interaction sites form a second interface that includes helix 6 of Bax and the BH4 region of Bcl-2. Loss-of-function mutations in the BH3 region of Bax and the BH1 region of Bcl-2 disrupted the BH3-BH1-3 interface, as expected. Surprisingly the second interface was also disrupted by these mutations. Similarly, a loss-of-function mutation in the BH4 region of Bcl-2 that forms part of the second interface also disrupted both interfaces. As expected, both kinds of mutation abolished Bcl-2-mediated inhibition of Bax oligomerization in detergent micelles. Therefore, Bcl-2 binds Bax through two interdependent interfaces to inhibit the pro-apoptotic oligomerization of Bax. PMID- 20584904 TI - Regulation of AMPA receptor trafficking and function by glycogen synthase kinase 3. AB - Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a multifunctional kinase implicated in neuronal development, mood stabilization, and neurodegeneration. However, the synaptic actions of GSK-3 are largely unknown. In this study, we examined the impact of GSK-3 on AMPA receptor (AMPAR) channels, the major mediator of excitatory transmission, in cortical neurons. Application of GSK-3 inhibitors or knockdown of GSK-3 caused a significant reduction of the amplitude of miniature excitatory postsynaptic current (mEPSC), a readout of the unitary strength of synaptic AMPARs. Treatment with GSK-3 inhibitors also decreased surface and synaptic GluR1 clusters on dendrites and increased internalized GluR1 in cortical cultures. Rab5, the small GTPase controlling the transport from plasma membrane to early endosomes, was activated by GSK-3 inhibitors. Knockdown of Rab5 prevented GSK-3 inhibitors from regulating mEPSC amplitude. Guanyl nucleotide dissociation inhibitor (GDI), which regulates the cycle of Rab5 between membrane and cytosol, formed an increased complex with Rab5 after treatment with GSK-3 inhibitors. Blocking the function of GDI occluded the effect of GSK-3 inhibitors on mEPSC amplitude. In cells transfected with the non-phosphorylatable GDI mutant, GDI(S45A), GSK-3 inhibitors lost the capability to regulate GDI-Rab5 complex, mEPSC amplitude, and AMPAR surface expression. These results suggest that GSK-3, via altering the GDI-Rab5 complex, regulates Rab5-mediated endocytosis of AMPARs. It provides a potential mechanism underlying the role of GSK-3 in synaptic transmission and plasticity. PMID- 20584905 TI - Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions. AB - Kv7 channels, especially Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3), are key determinants for membrane excitability in the brain. Some chemical modulators of KCNQ channels are in development for use as anti-epileptic drugs, such as retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)), which was recently approved for clinical use. In addition, several other compounds were also reported to potentiate activity of the Kv7 channels. It is therefore of interest to investigate compound-channel interactions, so that more insights may be gained to aid future development of therapeutics. We have conducted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic absorption spectrometry. Here, we report the characterization of a series of new structures that display isoform specificity and induce a marked reduction of deactivation distinct from that of retigabine. Furthermore, KCNQ2(W236L), a previously reported mutation that abolishes sensitivity to retigabine, remains fully sensitive to these compounds. This result, together with mutagenesis and other studies, suggests that the reported compounds confer a unique mode of action and involve new molecular determinants on the channel protein, consistent with the idea of recognizing a new site on channel protein. PMID- 20584906 TI - Methionine sulfoxide reductase B1 (MsrB1) recovers TRPM6 channel activity during oxidative stress. AB - Mg(2+) is an essential ion for many cellular processes, including protein synthesis, nucleic acid stability, and numerous enzymatic reactions. Mg(2+) homeostasis in mammals depends on the equilibrium between intestinal absorption, renal excretion, and exchange with bone. The transient receptor potential melastatin type 6 (TRPM6) is an epithelial Mg(2+) channel, which is abundantly expressed in the luminal membrane of the renal and intestinal cells. It functions as the gatekeeper of transepithelial Mg(2+) transport. Remarkably, TRPM6 combines a Mg(2+)-permeable channel with an alpha-kinase domain. Here, by the Ras recruitment system, we identified methionine sulfoxide reductase B1 (MsrB1) as an interacting protein of the TRPM6 alpha-kinase domain. Importantly, MsrB1 and TRPM6 are both present in the renal Mg(2+)-transporting distal convoluted tubules. MsrB1 has no effect on TRPM6 channel activity in the normoxic conditions. However, hydrogen peroxide (H(2)O(2)) decreased TRPM6 channel activity. Co-expression of MsrB1 with TRPM6 attenuated the inhibitory effect of H(2)O(2) (TRPM6, 67 +/- 5% of control; TRPM6 + MsrB1, 81 +/- 5% of control). Cell surface biotinylation assays showed that H(2)O(2) treatment does not affect the expression of TRPM6 at the plasma membrane. Next, mutation of Met(1755) to Ala in TRPM6 reduced the inhibitory effect of H(2)O(2) on TRPM6 channel activity (TRPM6 M1755A: 84 +/- 10% of control), thereby mimicking the action of MsrB1. Thus, these data suggest that MsrB1 recovers TRPM6 channel activity by reducing the oxidation of Met(1755) and could, thereby, function as a modulator of TRPM6 during oxidative stress. PMID- 20584907 TI - Identification of the chromophores involved in aggregation-dependent energy quenching of the monomeric photosystem II antenna protein Lhcb5. AB - Non-photochemical quenching (NPQ) of excess absorbed light energy is a fundamental process that regulates photosynthetic light harvesting in higher plants. Among several proposed NPQ mechanisms, aggregation-dependent quenching (ADQ) and charge transfer quenching have received the most attention. In vitro spectroscopic features of both mechanisms correlate with very similar signals detected in more intact systems and in vivo, where full NPQ can be observed. A major difference between the models is the proposed quenching site, which is predominantly the major trimeric light-harvesting complex II in ADQ and exclusively monomeric Lhcb proteins in charge transfer quenching. Here, we studied ADQ in both monomeric and trimeric Lhcb proteins, investigating the activities of each antenna subunit and their dependence on zeaxanthin, a major modulator of NPQ in vivo. We found that monomeric Lhcb proteins undergo stronger quenching than light-harvesting complex II during aggregation and that this is enhanced by binding to zeaxanthin, as occurs during NPQ in vivo. Finally, the analysis of Lhcb5 mutants showed that chlorophyll 612 and 613, in close contact with lutein bound at site L1, are important facilitators of ADQ. PMID- 20584908 TI - Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II. AB - Angiotensin II (ANG II) stimulates renal tubular reabsorption of NaCl by targeting Na(+)/H(+) exchanger NHE3. We have shown previously that inositol 1,4,5 triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concentration ([Ca(2+)](i)). In this study, we investigated the role of IRBIT in mediating NHE3 activation by ANG II. IRBIT is abundantly expressed in the proximal tubules where NHE3 is located. ANG II at physiological concentrations stimulates NHE3 transport activity in a model proximal tubule cell line. ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overexpression of IRBIT enhanced the effect of ANG II on NHE3. ANG II transiently increased binding of IRBIT to NHE3 at 5 min but became dissociated by 45 min. In comparison, it took at least 15 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression. The stimulation of NHE3 by ANG II was dependent on changes in [Ca(2+)](i) and Ca(2+)/calmodulin-dependent protein kinases II. Inhibition of CaMKII completely blocked the ANG II-induced binding of IRBIT to NHE3 and the increase in NHE3 surface abundance. Several serine residues of IRBIT are thought to be important for IRBIT binding. Mutations of Ser-68, Ser-71, and Ser-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity. In conclusion, our current findings demonstrate that IRBIT is critically involved in mediating activation of NHE3 by ANG II via a Ca(2+)/calmodulin-dependent protein kinases II-dependent pathway. PMID- 20584909 TI - Absence of DICER in monocytes and its regulation by HIV-1. AB - MicroRNAs (miRNAs) are a class of small RNA molecules that function to control gene expression and restrict viral replication in host cells. The production of miRNAs is believed to be dependent upon the DICER enzyme. Available evidence suggests that in T lymphocytes, HIV-1 can both suppress and co-opt the host's miRNA pathway for its own benefit. In this study, we examined the state of miRNA production in monocytes and macrophages as well as the consequences of viral infection upon the production of miRNA. Monocytes in general express low amounts of miRNA-related proteins, and DICER in particular could not be detected until after monocytes were differentiated into macrophages. In the case where HIV-1 was present prior to differentiation, the expression of DICER was suppressed. MicroRNA chip results for RNA isolated from transfected and treated cells indicated that a drop in miRNA production coincided with DICER protein suppression in macrophages. We found that the expression of DICER in monocytes is restricted by miR-106a, but HIV-1 suppressed DICER expression via the viral gene Vpr. Additionally, analysis of miRNA expression in monocytes and macrophages revealed evidence that some miRNAs can be processed by both DICER and PIWIL4. Results presented here have implications for both the pathology of viral infections in macrophages and the biogenesis of miRNAs. First, HIV-1 suppresses the expression and function of DICER in macrophages via a previously unknown mechanism. Second, the presence of miRNAs in monocytes lacking DICER indicates that some miRNAs can be generated by proteins other than DICER. PMID- 20584911 TI - Sean Morrison: A root and branch approach to stem cells. PMID- 20584910 TI - Structural insights into serine-rich fimbriae from Gram-positive bacteria. AB - The serine-rich repeat family of fimbriae play important roles in the pathogenesis of streptococci and staphylococci. Despite recent attention, their finer structural details and precise adhesion mechanisms have yet to be determined. Fap1 (Fimbriae-associated protein 1) is the major structural subunit of serine-rich repeat fimbriae from Streptococcus parasanguinis and plays an essential role in fimbrial biogenesis, adhesion, and the early stages of dental plaque formation. Combining multidisciplinary, high resolution structural studies with biological assays, we provide new structural insight into adhesion by Fap1. We propose a model in which the serine-rich repeats of Fap1 subunits form an extended structure that projects the N-terminal globular domains away from the bacterial surface for adhesion to the salivary pellicle. We also uncover a novel pH-dependent conformational change that modulates adhesion and likely plays a role in survival in acidic environments. PMID- 20584913 TI - Joining the interface: a site for Nmd3 association on 60S ribosome subunits. AB - The adaptor protein Nmd3 is required for Crm1-dependent export of large ribosomal subunits from the nucleus. In this issue, Sengupta et al. (2010. J. Cell Biol. doi:10.1083/jcb.201001124) identify a binding site for yeast Nmd3 on 60S ribosomal subunits using cryoelectron microscopy and suggest a conformational model for its release in the cytoplasm. The study provides the first detailed structural description of a ribosome biogenesis factor in complex with the large subunit. PMID- 20584914 TI - Neighborly relations: cadherins and mechanotransduction. AB - Cell-cell adhesions are sites where cells experience and resist tugging forces. It has long been postulated, but not directly tested, that cadherin adhesion molecules may serve in mechanotransduction at cell-cell contacts. In this issue, Le Duc et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201001149) provide direct evidence that E-cadherin participates in a mechanosensing pathway that regulates the actomyosin cytoskeleton to modulate cell stiffness in response to pulling force. PMID- 20584912 TI - Clearance of apoptotic cells: implications in health and disease. AB - Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies. PMID- 20584916 TI - Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. AB - Cell surface receptors integrate chemical and mechanical cues to regulate a wide range of biological processes. Integrin complexes are the mechanotransducers between the extracellular matrix and the actomyosin cytoskeleton. By analogy, cadherin complexes may function as mechanosensors at cell-cell junctions, but this capacity of cadherins has not been directly demonstrated. Furthermore, the molecular composition of the link between E-cadherin and actin, which is needed to sustain such a function, is unresolved. In this study, we describe nanomechanical measurements demonstrating that E-cadherin complexes are functional mechanosensors that transmit force between F-actin and E-cadherin. Imaging experiments reveal that intercellular forces coincide with vinculin accumulation at actin-anchored cadherin adhesions, and nanomechanical measurements show that vinculin potentiates the E-cadherin mechanosensory response. These investigations directly demonstrate the mechanosensory capacity of the E-cadherin complex and identify a novel function for vinculin at cell-cell junctions. These findings have implications for barrier function, morphogenesis, cell migration, and invasion and may extend to all soft tissues in which classical cadherins regulate cell-cell adhesion. PMID- 20584915 TI - Characterization of the nuclear export adaptor protein Nmd3 in association with the 60S ribosomal subunit. AB - The nucleocytoplasmic shuttling protein Nmd3 is an adaptor for export of the 60S ribosomal subunit from the nucleus. Nmd3 binds to nascent 60S subunits in the nucleus and recruits the export receptor Crm1 to facilitate passage through the nuclear pore complex. In this study, we present a cryoelectron microscopy (cryo EM) reconstruction of the 60S subunit in complex with Nmd3 from Saccharomyces cerevisiae. The density corresponding to Nmd3 is directly visible in the cryo-EM map and is attached to the regions around helices 38, 69, and 95 of the 25S ribosomal RNA (rRNA), the helix 95 region being adjacent to the protein Rpl10. We identify the intersubunit side of the large subunit as the binding site for Nmd3. rRNA protection experiments corroborate the structural data. Furthermore, Nmd3 binding to 60S subunits is blocked in 80S ribosomes, which is consistent with the assigned binding site on the subunit joining face. This cryo-EM map is a first step toward a molecular understanding of the functional role and release mechanism of Nmd3. PMID- 20584918 TI - Retraction. SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos. PMID- 20584917 TI - DNA polymerases nu and theta are required for efficient immunoglobulin V gene diversification in chicken. AB - The chicken DT40 B lymphocyte line diversifies its immunoglobulin (Ig) V genes through translesion DNA synthesis-dependent point mutations (Ig hypermutation) and homologous recombination (HR)-dependent Ig gene conversion. The error-prone biochemical characteristic of the A family DNA polymerases Polnu and Pol led us to explore the role of these polymerases in Ig gene diversification in DT40 cells. Disruption of both polymerases causes a significant decrease in Ig gene conversion events, although POLN(-/-)/POLQ(-/-) cells exhibit no prominent defect in HR-mediated DNA repair, as indicated by no increase in sensitivity to camptothecin. Poleta has also been previously implicated in Ig gene conversion. We show that a POLH(-/-)/POLN(-/-)/POLQ(-/-) triple mutant displays no Ig gene conversion and reduced Ig hypermutation. Together, these data define a role for Polnu and Pol in recombination and suggest that the DNA synthesis associated with Ig gene conversion is accounted for by three specialized DNA polymerases. PMID- 20584919 TI - Ethical analysis of withdrawing ventricular assist device support. AB - OBJECTIVE: To describe a series of patients with heart failure supported with a ventricular assist device (VAD) who requested (or whose surrogates requested) withdrawal of VAD support and the legal and ethical aspects pertaining to these requests. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients at Mayo Clinic, Rochester, MN, from March 1, 2003, through January 31, 2009, who requested (or whose surrogates requested) withdrawal of VAD support and for whom the requests were fulfilled. We then explored the legal and ethical permissibility of carrying out such requests. RESULTS: The median age of the 14 patients identified (13 men, 1 woman) was 57 years. Requests were made by 2 patients and 12 surrogates. None of the patients' available advance directives mentioned the VAD. For 11 patients, multidisciplinary care conferences were held before withdrawal of VAD support. Only 1 patient had an ethics consultation. All 14 patients died within 1 day of withdrawal of VAD support. CONCLUSION: Patients have the right to refuse or request the withdrawal of any unwanted treatment, and we argue that this right extends to VAD support. We also argue that the cause of death in these cases is the underlying heart disease, not assisted suicide or euthanasia. Therefore, patients with heart failure supported with VADs or their surrogates may request withdrawal of this treatment. In our view, carrying out such requests is permissible in accordance with the principles that apply to withdrawing other life-sustaining treatments. PMID- 20584920 TI - The role of nucleus accumbens shell in learning about neutral versus excitatory stimuli during Pavlovian fear conditioning. AB - We studied the role of nucleus accumbens shell (AcbSh) in Pavlovian fear conditioning. Rats were trained to fear conditioned stimulus A (CSA) in Stage I, which was then presented in compound with a neutral stimulus and paired with shock in Stage II. AcbSh lesions had no effect on fear-learning to CSA in Stage I, but selectively prevented learning about the neutral conditioned stimulus (CS) in Stage II. These results add to a growing body of evidence indicating an important role for the ventral striatum in fear-learning. They suggest that the ventral striatum and AcbSh, in particular, directs learning toward or away from a CS as a consequence of how well that CS predicts the shock unconditioned stimulus (US). AcbSh is required to reduce the processing of established predictors, thereby permitting neutral or less predictive stimuli to be learned about. PMID- 20584925 TI - Clorgyline-mediated reversal of neurological deficits in a Complexin 2 knockout mouse. AB - Complexin 2 is a protein modulator of neurotransmitter release that is downregulated in humans suffering from depression, animal models of depression and neurological disorders such as Huntington's disease in which depression is a major symptom. Although complexin 2 knockout (Cplx2-/-) mice are overtly normal, they show significant abnormalities in cognitive function and synaptic plasticity. Here we show that Cplx2-/- mice also have disturbances in emotional behaviours that include abnormal social interactions and depressive-like behaviour. Since neurotransmitter deficiencies are thought to underlie depression, we examined neurotransmitter levels in Cplx2-/- mice and found a significant decrease in levels of noradrenaline and the serotonin metabolite 5 hydroxyindoleacetic acid in the hippocampus. Chronic treatment with clorgyline, an irreversible inhibitor of monoamine oxidase A, restored hippocampal noradrenaline to normal levels (from 60 to 97% of vehicle-treated Cplx2+/+ mice, P<0.001), and reversed the behavioural deficits seen in Cplx2-/- mice. For example, clorgyline-treated Cplx2-/- mice spent significantly more time interacting with a novel visitor mouse compared with vehicle-treated Cplx2-/- mice in the social recognition test (34 compared with 13%, P<0.01). We were also able to reverse the selective deficit seen in mossy fibre-long-term potentiation (MF-LTP) in Cplx2-/- mice using the noradrenergic agonist isoprenaline. Pre treatment with isoprenaline in vitro increased MF-LTP by 125% (P<0.001), thus restoring it to control levels. Our data strongly support the idea that complexin 2 is a key player in normal neurological function, and that downregulation of complexin 2 could lead to changes in neurotransmitter release sufficient to cause significant behavioural abnormalities such as depression. PMID- 20584927 TI - Access to treatment for multiple sclerosis must be based on science, not hope. PMID- 20584926 TI - The early-onset torsion dystonia-associated protein, torsinA, is a homeostatic regulator of endoplasmic reticulum stress response. AB - Early-onset torsion dystonia is the most severe heritable form of dystonia, a human movement disorder that typically starts during a developmental window in early adolescence. Deletion in the DYT1 gene, encoding the torsinA protein, is responsible for this dominantly inherited disorder, which is non-degenerative and exhibits reduced penetrance among carriers. Here, we explore the hypothesis that deficits in torsinA function result in an increased vulnerability to stress associated with protein folding and processing in the endoplasmic reticulum (ER), where torsinA is located. Using an in vivo quantitative readout for the ER stress response, we evaluated the consequences of torsinA mutations in transgenic nematodes expressing variants of human torsinA. This analysis revealed that, normally, torsinA serves a protective function to maintain a homeostatic threshold against ER stress. Furthermore, we show that the buffering capacity of torsinA is greatly diminished by the DYT1-associated deletion or mutations that prevent its translocation to the ER, block ATPase activity, or increase the levels of torsinA in the nuclear envelope versus ER. Combinations of transgenic Caenorhabditis elegans designed to mimic clinically relevant genetic modifiers of disease susceptibility also exhibit a direct functional correlation to changes in the ER stress response. Furthermore, using mouse embryonic fibroblasts (MEFs) from torsinA knockout mice, we demonstrated that loss of endogenous torsinA results in enhanced sensitivity to ER stress. This study extends our understanding of molecular mechanisms underlying dystonia, and establishes a new functional paradigm to evaluate therapeutic strategies to compensate for reduced torsinA activity in the ER as a means to restore homeostatic balance and neuronal function. PMID- 20584928 TI - Coordination, childhood weight gain and obesity. PMID- 20584930 TI - Entamoeba histolytica liver abscess. PMID- 20584931 TI - Performing socially sensitive research in the 21st century. PMID- 20584932 TI - Trajectories of relative weight and waist circumference among children with and without developmental coordination disorder. AB - BACKGROUND: Children with developmental coordination disorder have been found to be less likely to participate in physical activities and therefore may be at increased risk of overweight and obesity. We examined the longitudinal course of relative weight and waist circumference among school-aged children with and without possible developmental coordination disorder. METHODS: We received permission from 75 (83%) of 92 schools in southwestern Ontario, Canada, to enrol children in the fourth grade (ages 9 and 10 at baseline). Informed consent from the parents of 2278 (95.8%) of 2378 children in these schools was obtained at baseline. The main outcome measures were body mass index (BMI) and waist circumference. Children were followed up over two years, from the spring of 2005 to the spring of 2007. RESULTS: Over the course of the study, we identified 111 children (46 boys and 65 girls) who had possible developmental coordination disorder. These children had a higher mean BMI and waist circumference at baseline than did those without the disorder; these differences persisted or increased slightly over time. Children with possible developmental coordination disorder were also at persistently greater risk of overweight (odds ratio [OR] 3.44, 95% confidence interval [CI] 2.34-5.07) and obesity (OR 4.00, 95% CI 2.57 6.21) over the course of the study. INTERPRETATION: Our findings showed that children with possible developmental coordination disorder were at greater risk of overweight and obesity than children without the disorder. This risk did not diminish over the study period. PMID- 20584933 TI - An unusual presentation of amebic liver abscesses. PMID- 20584936 TI - G8 Summit: a final test of credibility. PMID- 20584934 TI - Migration and health in Canada: health in the global village. AB - BACKGROUND: Immigration has been and remains an important force shaping Canadian demography and identity. Health characteristics associated with the movement of large numbers of people have current and future implications for migrants, health practitioners and health systems. We aimed to identify demographics and health status data for migrant populations in Canada. METHODS: We systematically searched Ovid MEDLINE (1996-2009) and other relevant web-based databases to examine immigrant selection processes, demographic statistics, health status from population studies and health service implications associated with migration to Canada. Studies and data were selected based on relevance, use of recent data and quality. RESULTS: Currently, immigration represents two-thirds of Canada's population growth, and immigrants make up more than 20% of the nation's population. Both of these metrics are expected to increase. In general, newly arriving immigrants are healthier than the Canadian population, but over time there is a decline in this healthy immigrant effect. Immigrants and children born to new immigrants represent growing cohorts; in some metropolitan regions of Canada, they represent the majority of the patient population. Access to health services and health conditions of some migrant populations differ from patterns among Canadian-born patients, and these disparities have implications for preventive care and provision of health services. INTERPRETATION: Because the health characteristics of some migrant populations vary according to their origin and experience, improved understanding of the scope and nature of the immigration process will help practitioners who will be increasingly involved in the care of immigrant populations, including prevention, early detection of disease and treatment. PMID- 20584937 TI - G8 Summit: sorting out the supplicants. PMID- 20584938 TI - Human rights group alleges Bush administration and physicians conducted illegal medical research on detainees. PMID- 20584939 TI - Former senior editor at The Lancet cries foul over firing for "gross misconduct". PMID- 20584940 TI - European impasse over patients' rights directive may be at an end. PMID- 20584942 TI - Brain. Editorial. PMID- 20584941 TI - RTM3, which controls long-distance movement of potyviruses, is a member of a new plant gene family encoding a meprin and TRAF homology domain-containing protein. AB - Restriction of long-distance movement of several potyviruses in Arabidopsis (Arabidopsis thaliana) is controlled by at least three dominant restricted TEV movement (RTM) genes, named RTM1, RTM2, and RTM3. RTM1 encodes a protein belonging to the jacalin family, and RTM2 encodes a protein that has similarities to small heat shock proteins. In this article, we describe the positional cloning of RTM3, which encodes a protein belonging to an undescribed protein family of 29 members that has a meprin and TRAF homology (MATH) domain in its amino-terminal region and a coiled-coil domain at its carboxy-terminal end. Involvement in the RTM resistance system is the first biological function experimentally identified for a member of this new gene family in plants. Our analyses showed that the coiled-coil domain is not only highly conserved between RTM3-homologous MATH containing proteins but also in proteins lacking a MATH domain. The cluster organization of the RTM3 homologs in the Arabidopsis genome suggests the role of duplication events in shaping the evolutionary history of this gene family, including the possibility of deletion or duplication of one or the other domain. Protein-protein interaction experiments revealed RTM3 self-interaction as well as an RTM1-RTM3 interaction. However, no interaction has been detected involving RTM2 or the potyviral coat protein previously shown to be the determinant necessary to overcome the RTM resistance. Taken together, these observations strongly suggest the RTM proteins might form a multiprotein complex in the resistance mechanism to block the long-distance movement of potyviruses. PMID- 20584943 TI - Predicting a window of therapeutic opportunity in multiple sclerosis. PMID- 20584944 TI - The age of single-gene neurological disorders is not dead. PMID- 20584945 TI - Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? AB - The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical physiological notions about vitamin D have recently been challenged and the main new findings are summarized. This vitamin could have an important immunological role involving a number of organs and pathologies, including autoimmune diseases and multiple sclerosis. Furthermore, human requirements for this vitamin are much higher than previously thought, and in medium- or high-latitude countries, they might not be met in the majority of the general population due to a lack of sunshine and an increasingly urbanized lifestyle. Thereafter, the different types of studies that have helped to implicate hypovitaminosis D as a risk factor for multiple sclerosis are reviewed. In experimental autoimmune encephalomyelitis, vitamin D has been shown to play a significant immunological role. Diverse epidemiological studies suggest that a direct chain of causality exists in the general population between latitude, exposure to the sun, vitamin D status and the risk of multiple sclerosis. New epidemiological analyses from France support the existence of this chain of links. Recently reported immunological findings in patients with multiple sclerosis have consistently shown that vitamin D significantly influences regulatory T lymphocyte cells, whose role is well known in the pathogenesis of the disease. Lastly, in a number of studies on serum levels of vitamin D in multiple sclerosis, an insufficiency was observed in the great majority of patients, including at the earliest stages of the disease. The questionable specificity and significance of such results is detailed here. Based on a final global analysis of the cumulative significance of these different types of findings, it would appear likely that hypovitaminosis D is one of the risk factors for multiple sclerosis. PMID- 20584946 TI - Does corticobasal degeneration exist? A clinicopathological re-evaluation. AB - The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed. PMID- 20584947 TI - National emergency department targets reach the shores of Australasia. PMID- 20584948 TI - Reliability and validity of an Italian four-level emergency triage system. AB - OBJECTIVES: To measure the reliability and predictive validity of a four-level triage system (I-4L). METHODS: This observational study was conducted in an urban hospital. Five nurses were randomly selected to assign a triage level to 246 paper scenarios, using the I-4L model. The I-4L model is a four-level triage system: urgency category (UC) 1 requires immediate response; UCs 2, 3 and 4 require assessment within 20, 60 and 120 min, respectively. Weighted kappa statistics were used to measure the inter-rater and intrarater reliability of the triage tool and the validity of the model was assessed based on the accuracy in predicting admission and in predicting a reference standard's triage code. RESULTS: The I-4L model's inter-rater reliability was kappa=0.73 (95% CI 0.67 to 0.79), and the intrarater reliability was kappa=0.82 (95% CI 0.67 to 0.96). Its accuracy of triage rating for admission and for prediction of a reference standard's triage code was good: 79% (95% CI 73% to 86%) and 93% (95% CI 89% to 96%), respectively. The percentages of patients admitted per triage level using the I-4L model was: 100% UC 1; 42% UC 2; 6% UC 3; and 2% UC 4. CONCLUSIONS: The I 4L triage model shows a good inter-rater and intrarater reliability for rating triage acuity and for accuracy in patient admission and prediction of a reference standard's triage code. PMID- 20584949 TI - Characteristics of medication overdose presentations to the ED: how do they differ from illicit drug overdose and self-harm cases? AB - BACKGROUND: Medication overdose accounts for >80% of hospital presentations for self-harm. Previous research has identified typical characteristics of medication overdose cases; however, these cases have not been well differentiated from other similar presentations, namely (1) illicit drug overdose and (2) self-harm by means other than overdose. METHOD: A 12-month audit of medication overdose cases (both intentional and unintentional) attending the emergency department (ED) of a major metropolitan public hospital in Melbourne, Australia was conducted. Comparison was made with patients attending for illicit drug overdose or for self harm by means other than overdose. RESULTS: Medication overdose cases (n=453) showed a broadly comparable profile with those found in earlier studies (predominantly female gender, aged in their 30s and referred for psychosocial assessment). A similar though not identical profile was noted for self-harm cases (n=545). In contrast, patients attending for illicit drug overdose (n=409) could be characterised as male, in their 20s and not referred for psychosocial assessment. Illicit drug overdose cases were more likely than either the medication overdose or self-harm cases to be triaged in the most urgent category (19.3, 3.8 and 3.9% respectively), suggesting a high level of acuity in this group. However, the illicit drug overdose group on average spent less time in the ED than medication overdose patients, and were less likely to require hospital admission. CONCLUSION: On both demographic and treatment variables, patients attending the ED following a medication overdose more closely resemble those attending for self-harm by means other than overdose than those attending for illicit drug overdose. PMID- 20584950 TI - Access block and overcrowding in emergency departments: an empirical analysis. AB - OBJECTIVE: To quantify the determinants of the duration of time spent in an emergency department (ED) for patients who need admission to hospital. METHODS: A retrospective analysis of a year of administrative data on all patients presenting to 38 public hospital EDs in Victoria, Australia in 2005/2006. Individual administrative data on patient care time, defined as the time in the ED from first being seen by a treating doctor to admission, were analysed using parametric survival analysis (generalised gamma model). Patient times were regarded as censored if the patients died in the ED or were transferred to another hospital. The outcome measure was the elasticity of patient care time, calculated as the percentage change in time for a 1% change in continuous variables and a unit change in dichotomous variables. RESULTS: The mean patient care time was 396 min (95% CI 395 to 398). Reduced time in ED was associated with the number of nurses (elasticity=-2.38%; 95% CI -2.31 to -2.45); the number of beds (elasticity= -2.99%; 95% CI, -2.89 to -3.08); the number of doctors (elasticity=-0.235%; 95% CI -0.232 to -0.237). There was significant variation in the time spent in the ED across hospitals after adjustment for observable differences in patient and hospital characteristics. Overall an increase in hospital resources, as measured by the number of nurses, doctors and physical beds, is associated with a significant reduction in patient care time in the ED. CONCLUSION: Increasing hospital capacity is likely to reduce overcrowding in the average ED, but factors that determine congestion in individual hospitals need to be further investigated. PMID- 20584951 TI - A woman with peri-orbital emphysema. PMID- 20584952 TI - Predictors of important neurological causes of dizziness among patients presenting to the emergency department. AB - OBJECTIVES: Dizziness is a common presenting complaint in the emergency department (ED). This prospective study describes the incidence, causes and outcome of ED patients presenting with dizziness and tries to identify predictors of central neurological causes of dizziness. METHODS: Single-centre prospective observational study in a university teaching hospital ED in Hong Kong. All ED patients (> or = 18 years old) presenting with dizziness were recruited for 1 month. Symptoms, previous health, physical findings, diagnosis and disposition were recorded. The outcome at 3 months was evaluated using hospital records and telephone interviews. Follow-up was also performed at 55 months using computerised hospital records to identify patients with subsequent stroke and those who had died. RESULTS: 413 adults (65% female, mean 57 years) were recruited. The incidence of dizziness was 3.6% (413/11 319). Nausea and/or vomiting (46%) and headache (20%) were the commonest associated findings. Hypertension (33%) was the commonest previous illness. Central neurological causes of dizziness were found in 6% (23/413) of patients. Age > or = 65 years (OR=6.13, 95% CI 1.97 to 19.09), ataxia symptoms (OR=11.39, 95% CI 2.404 to 53.95), focal neurological symptoms (OR=11.78, 95% CI 1.61 to 86.29), and history of previous stroke (OR=3.89, 95% CI 1.12 to 13.46) and diabetes mellitus (OR=3.57, 95% CI 1.04 to 12.28) predicted central causes of dizziness. CONCLUSIONS: Most dizzy patients had benign causes. Several clinical factors favoured a diagnosis of central neurological causes of dizziness. PMID- 20584953 TI - Pott's puffy tumour: a rare complication from frontal sinusitis. PMID- 20584954 TI - Impact of a new daily rapid access medical clinic in a Scottish district general hospital. AB - BACKGROUND: Medical admissions to hospital in the UK are rising by approximately 10% per year. A Medical Assessment Unit (MAU) was opened to help deal with the rising influx of patients. The objectives of this study were to determine if a daily rapid access medical clinic could provide a safe alternative to hospital admission and aid safe discharge for medical patients. METHODS: The rapid access clinic was embedded within the MAU, utilising existing resources. Patients were allocated and reviewed by a senior acute medicine specialist registrar (SpR). Data were collected from January to September 2008. RESULTS: 74 patients seen in the clinic were analysed. 93% of these were managed in an ambulatory fashion, avoiding admission and saving a potential 280 bed days. The same day discharge rate of all patients seen and assessed in the MAU was increased from 17% to 26% (p<0.001), following institution of the clinic. The readmission rate fell from 8% to 4% (p=0.12). CONCLUSIONS: A daily rapid access medical clinic embedded within a MAU was piloted and allowed the safe management of a variety of medical complaints in an ambulatory fashion. It enabled an increase in the discharge rate of patients referred for admission by general practitioners. This seemed to be more robust than as evidenced previously by a trend towards lower readmission rates. These results were dependent on the presence of a senior clinical decision maker to facilitate safe discharges. PMID- 20584955 TI - Is time to closure a factor in the occurrence of infection in traumatic wounds? A prospective cohort study in a Dutch level 1 trauma centre. AB - BACKGROUND: The dogma that traumatic wounds should not be sutured after 6 h is based on an animal experiment by P L Friedrich in 1898. There is no adequately powered prospective study on this cut-off of 6 h to confirm or disprove the dogma. The aim of this study was to provide evidence against the dogma that wounds should be sutured within 6 h after trauma. METHOD: 425 patients were included in a prospective cohort study. Patients' wounds were closed, independent of time after trauma. All patients were seen after 7-10 days for removal of stitches and wound control on infection. RESULTS: Of the 425 patients, 17 were lost to follow-up. Of the remaining 408 patients, 45 had wounds older than 6 h after trauma. At follow-up 372 patients (91%) had no infection and 36 patients had redness of the suture sites or worse. 11 patients (2.7%) had general redness or pus. Of those with a wound older than 6 h, three of 45 (6.7%) wounds were infected, versus 30 of 363 (9.1%) in wounds younger than 6 h (p=0.59). CONCLUSION: In everyday practice wounds are sutured regardless of elapsed time. Here an attempt was made to present the evidence for this daily routine, contrary to Friedrich's Dogma. PMID- 20584956 TI - Integrated care pathway for self-harm: our way forward. AB - BACKGROUND: Balancing pressures of the 4-h wait in Accident and Emergency (A&E) and the National Institute for Clinical Excellence (NICE) requirement for a psychosocial assessment (PSA) before leaving hospital for patients presenting with self-harm is a challenge. This paper suggests a new method for coping with this demand. METHODS: A score of 5 or above on the Modified Sad Persons Scale (MSPS), rated by general hospital staff, would result in an automatic admission to the general hospital for detailed PSA by the dedicated liaison psychiatry team the following day. RESULTS: Most patients are usually admitted due to medical concerns. Only a small number of patients needed further psychiatric inpatient admission. CONCLUSIONS: This integrated care pathway (ICP) is evidence of true multidisciplinary working resulting in mutually beneficial outcomes for both the acute and mental health trusts. PMID- 20584957 TI - Posterior reversible encephalopathy syndrome. AB - Posterior reversible encephalopathy syndrome is a recently described clinicoradiological entity. Neuroimaging is very demonstrative and can be the first clue to the diagnosis. Common causes of posterior reversible encephalopathy syndrome are hypertensive encephalopathy, immunosuppressive treatment, renal failure and eclampsia. Its pathogenesis remains poorly understood. Clinical findings are not sufficiently specific; however, neuroimaging is often characteristic. PMID- 20584958 TI - Prevalence of cocaine use among patients attending the emergency department with chest pain. AB - INTRODUCTION: Cocaine is the only drug to show a rise in misuse between 1996 and 2007 in England and Wales. It can cause chest pain and myocardial infarction. This study assessed the prevalence of cocaine use in patients presenting with chest pain, and determined the association between cocaine use and chest pain. METHODS: Patients presenting with chest pain had a urine sample collected at presentation. Each patient with chest pain was matched with a non-chest pain control. Demographic detail, drug history and clinical outcome was recorded, samples anonymised and subsequently tested for cocaine and metabolites. RESULTS: Of the 1469 patients, 101 (6.9%) tested positive for cocaine compared with 3.8% of controls (p<0.001). Men (8%) were more likely than women (5.1%) to test positive for cocaine. Two patients developed a myocardial infarction. Cocaine use was highest in those aged 18-30 years for both sexes and decreased with age. Cocaine-positive patients with chest pain were more likely to present in the evening, after midnight or at the weekend. Only 18% of all patients presenting with chest pain had a specific drug history recorded in their notes. CONCLUSIONS: As many patients do not admit to use of an illegal drug, routine testing would enable cocaine-related ischaemic events to be identified more easily but this remains controversial. As management of cocaine-induced chest pain is different from other causes of chest pain, doctors should routinely question patients with chest pain about cocaine use in addition to well recognised risk factors. PMID- 20584959 TI - Trauma-induced coagulopathy in severely injured patients: knowledge lost in translation? AB - BACKGROUND: Many guidelines exist on how to treat patients with multiple injuries correctly in an accident and emergency setting. The aim of the present work was to find out how well patients are treated focusing on trauma induced coagulopathy (TIC), and what anaesthetists involved in trauma care think about their own experiences with TIC. METHODS: In a retrospective chart review of patients with an Injury Severity Score (ISS) > or = 16 between October 2007 and October 2008. A total of 172 patients with multiple injuries (134 men, 38 women) were treated in the resuscitation room and underwent complete coagulation screening (international normalised ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT)). The presence of TIC was defined as INR>1.5 and aPTT>60 s or TT>15 s. Additionally, during the weekly anaesthesia and critical care grand round, a short questionnaire about TIC management was distributed to all anaesthetists involved in trauma care. RESULTS: Of the 172 patients with multiple injuries, 56 (32.6%) had TIC at admission to the resuscitation bay and 7 of these 56 (12.5%) received fresh-frozen plasma in the first hour of treatment. The mean of 55 anaesthetists thought that TIC could be corrected within about 30 min, although a chart review shows that it takes about 60 min to get complete laboratory based coagulation screening results. However, 70% of the doctors are not satisfied with the laboratory results they receive concerning TIC. CONCLUSIONS: There is an obvious discrepancy between the content of guidelines and the everyday practice. Future academic efforts in the area of trauma care should therefore focus more on the translational approach and the implementation of existing knowledge rather than on simply formulating guidelines. PMID- 20584960 TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Bet 1. PMID- 20584962 TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Bet 2. PMID- 20584963 TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Bet 3. PMID- 20584964 TI - Emergency Medical Services: a resource for victims of domestic violence? AB - BACKGROUND: Domestic violence (DV), also known as intimate partner violence (IPV), is one of the leading causes of serious injury among women of childbearing age. As first responders on the scene during DV calls where personal injuries have occurred, Emergency Medical Services (EMS) could routinely identify, report and assist victims of violence. Yet, little is known of the prevalence of DV calls in EMS practice, Emergency Medical Technicians' (EMT) knowledge and comfort in responding to such calls, or how they care for victims. METHOD: The objectives of this study were to assess EMTs' knowledge of and experience with providing care to victims of DV in the province of Ontario, Canada. Data were gathered through an online, short-answer survey. Survey data were analysed using basic frequency displays, and descriptive statistics are reported. RESULTS: Almost 500 EMTs participated in this study, the vast majority of whom (90%) attended at least one DV call in the preceding year, with 65% attending between 10 and 20 DV calls. The majority of respondents (84.5%) wished for more education and training on the issue. CONCLUSION: EMTs have frequent contact with victims of DV yet have received little education about the issue. The majority of those surveyed would like specific education and training on DV. PMID- 20584965 TI - Amisulpride overdose: suggested management of prolonged QTc. AB - A case of amisulpride overdose is presented and its effect on prolonging the QT (corrected) interval is discussed. Amisulpride is used for the treatment of schizophrenia and part of its safety profile is that is has no effect on the QT interval in therapeutic doses. The efficacy of intravenous calcium in restoring the QT to normal is proposed. PMID- 20584966 TI - A hero's woe: rotator cuff tear after performing the Heimlich manoeuvre. AB - The Heimlich manoeuvre is well recognised worldwide as an emergency technique to clear an obstructed airway. The potential for serious injury to the choking victim is also well reported. We report the first case of significant musculoskeletal injury suffered by a rescuer performing the Heimlich manoeuvre. He eventually made a full recovery from his injury. However, we need to be aware of the possibility of injury in the rescuer as well as the rescued. PMID- 20584968 TI - Caregiving in a patient's place of residence: turnover of direct care workers in home care and hospice agencies. AB - OBJECTIVE: High turnover and staff shortages among home care and hospice workers may compromise the quality and availability of in-home care. This study explores turnover rates of direct care workers for home care and hospice agencies. METHODS: OLS (ordinary least square) regression models are run using organizational data from 93 home care agencies and 29 hospice agencies in North Carolina. RESULTS: Home care agencies have higher total turnover rates than hospice agencies, but profit status may be an important covariate. Higher unemployment rates are associated with lower voluntary turnover. Agencies that do not offer health benefits experience higher involuntary turnover. CONCLUSION: Differences in turnover between hospice and home health agencies suggest that organizational characteristics of hospice care contribute to lower turnover rates. However, the variation in turnover rates is not fully explained by the proposed multivariate models. Future research should explore individual and structural-level variables that affect voluntary and involuntary turnover in these settings. PMID- 20584969 TI - Strontium ranelate decreases receptor activator of nuclear factor-KappaB ligand induced osteoclastic differentiation in vitro: involvement of the calcium-sensing receptor. AB - Strontium ranelate exerts both an anticatabolic and an anabolic effect on bone cells. To further investigate the mechanism by which strontium ranelate inhibits bone resorption, the effects of varying concentrations of Sr(o)(2+) on osteoclastic differentiation were studied using RAW 264.7 cells and peripheral blood monocytic cells (PBMCs). We report that increasing concentrations of Sr(o)(2+) down-regulate osteoclastic differentiation and tartrate-resistant acid phosphatase activity, leading to inhibition of bone resorption (-48% when PBMCs were cultured for 14 days in the presence of 2 mM Sr(o)(2+)). Using a dominant negative form of the calcium-sensing receptor (CaR) and a small interfering RNA approach, we provide evidences that the inhibition of osteoclast differentiation by Sr(o)(2+) is mediated by stimulation of the CaR. Moreover, our results suggest that the effects of Sr(o)(2+) on osteoclasts are, at least in part, mediated by inhibition of the receptor activator of nuclear factor-kappaB ligand (RANKL) induced nuclear translocation of nuclear factor-kappaB and activator protein-1 in the early stages of osteoclastic differentiation. In conclusion, our data indicate that Sr(2+) directly inhibits the formation of mature osteoclasts through down-regulation of RANKL-induced osteoclast differentiation and decreases osteoclast differentiation through the activation of the CaR. PMID- 20584970 TI - Transcellular passage of Neisseria meningitidis across a polarized respiratory epithelium. AB - Neisseria meningitidis is a major cause of sepsis and meningitis but is also a common commensal, present in the nasopharynx of between 8 and 20% of healthy individuals. During carriage, the bacterium is found on the surface of the nasopharyngeal epithelium and in deeper tissues, while to develop disease the meningococcus must spread across the respiratory epithelium and enter the systemic circulation. Therefore, investigating the pathways by which N. meningitidis crosses the epithelial barrier is relevant for understanding carriage and disease but has been hindered by the lack of appropriate models. Here, we have established a physiologically relevant model of the upper respiratory epithelial cell barrier to investigate the mechanisms responsible for traversal of N. meningitidis. Calu-3 human respiratory epithelial cells were grown on permeable cell culture membranes to form polarized monolayers of cells joined by tight junctions. We show that the meningococcus crosses the epithelial cell barrier by a transcellular route; traversal of the layer did not disrupt its integrity, and bacteria were detected within the cells of the monolayer. We demonstrate that successful traversal of the epithelial cell barrier by N. meningitidis requires expression of its type 4 pili (Tfp) and capsule and is dependent on the host cell microtubule network. The Calu-3 model should be suitable for dissecting the pathogenesis of infections caused by other respiratory pathogens, as well as the meningococcus. PMID- 20584971 TI - T-cell-independent immune responses do not require CXC ligand 13-mediated B1 cell migration. AB - The dynamic movement of B cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. B1a and B1b cells are enriched in the coelomic cavity, contribute to T-cell-independent (TI) antibody responses, and increase in number upon antigen exposure. B1 cell movement is largely governed by Cxc ligand 13 (Cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal B1 cells. In this study, we examined the role of Cxcl13-dependent B cell migration using Borrelia hermsii infection or intraperitoneal immunization with pneumococcal polysaccharide or 4-hydroxy-3-nitrophenyl-acetyl (NP)-Ficoll, all of which induce robust antibody responses from B1b cells. Surprisingly, we found that antibody responses to B. hermsii or to FhbA, an antigenic target of B1b cells, and the resolution of bacteremia were indistinguishable between wild type and Cxcl13-/- mice. Importantly, we did not observe an expansion of peritoneal B1b cell numbers in Cxcl13-/- mice. Nonetheless, mice that had resolved infection were resistant to reinfection, indicating that the peritoneal B1b cell reservoir is not required for controlling B. hermsii. Furthermore, despite a reduced peritoneal B1b compartment, immunization with pneumococcal polysaccharide vaccine yielded comparable antigen-specific antibody responses in wild-type and Cxcl13-/- mice and conferred protection against Streptococcus pneumoniae. Likewise, immunization with NP-Ficoll elicited similar antibody responses in wild-type and Cxcl13-/- mice. These data demonstrate that homing of B1 cells into the coelomic cavity is not a requirement for generating protective TI antibody responses, even when antigen is initially localized to this anatomical compartment. PMID- 20584972 TI - Interleukin-17A during local and systemic Staphylococcus aureus-induced arthritis in mice. AB - Staphylococcus aureus is one of the dominant pathogens that induce septic arthritis in immunocompromised hosts, e.g., patients suffering from rheumatoid arthritis treated with immunosuppressive drugs. S. aureus-induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Recently, interleukin-17A (IL-17A) has been discovered to be an important mediator of aseptic arthritis both in mice and humans, but its function in S. aureus-induced arthritis is largely unknown. Here, we investigated the role of IL 17A in host defense against arthritis following systemic and local S. aureus infection in vivo. IL-17A knockout mice and wild-type mice were inoculated systemically (intravenously) or locally (intra-articularly) with S. aureus. During systemic infection, IL-17A knockout mice lost significantly more weight than the wild-type mice did, but no differences were found in the mortality rate. The absence of IL-17A had no impact on clinical arthritis development but led to increased histopathological erosivity late during systemic S. aureus infection. Bacterial clearance in kidneys was increased in IL-17A knockout mice compared to the level in wild-type mice only 1 day after bacterial inoculation. During systemic S. aureus infection, serum IL-17F protein levels and mRNA levels in the lymph nodes were elevated in the IL-17A knockout mice compared to the level in wild-type mice. In contrast to systemic infection, the IL-17A knockout mice had increased synovitis and erosions and locally decreased clearance of bacteria 3 days after local bacterial inoculation. On the basis of these findings, we suggest that IL-17A is more important in local host defense than in systemic host defense against S. aureus-induced arthritis. PMID- 20584973 TI - Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis. AB - Batrachochytrium dendrobatidis is a chytrid fungus that causes the lethal skin disease chytridiomycosis in amphibians. It is regarded as an emerging infectious disease affecting diverse amphibian populations in many parts of the world. Because there are few model amphibian species for immunological studies, little is known about immune defenses against B. dendrobatidis. We show here that the South African clawed frog, Xenopus laevis, is a suitable model for investigating immunity to this pathogen. After an experimental exposure, a mild infection developed over 20 to 30 days and declined by 45 days postexposure. Either purified antimicrobial peptides or mixtures of peptides in the skin mucus inhibited B. dendrobatidis growth in vitro. Skin peptide secretion was maximally induced by injection of norepinephrine, and this treatment resulted in sustained skin peptide depletion and increased susceptibility to infection. Sublethal X irradiation of frogs decreased leukocyte numbers in the spleen and resulted in greater susceptibility to infection. Immunization against B. dendrobatidis induced elevated pathogen-specific IgM and IgY serum antibodies. Mucus secretions from X. laevis previously exposed to B. dendrobatidis contained significant amounts of IgM, IgY, and IgX antibodies that bind to B. dendrobatidis. These data strongly suggest that both innate and adaptive immune defenses are involved in the resistance of X. laevis to lethal B. dendrobatidis infections. PMID- 20584974 TI - Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge. AB - Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbAI) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbAI dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbAI and 35000HPhgbAII, respectively). Pigs immunized with the nHgbAI/MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbAI but not heterologous strain 35000HPhgbAII, as evidenced by the isolation of only strain 35000HPhgbAII from nHgbAI-immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbAI-immunized animals challenged with strains 35000HPhgbAI but not those challenged with strain 35000HPhgbAII. Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbAI/MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbAI/Freund's vaccine; however, anti-nHgbAI from both studies bound whole cells of 35000HPhgbAI better than 35000HPhgbAII and partially blocked hemoglobin binding to nHgbAI. In conclusion, despite eliciting lower antibody ELISA activity than the nHgbAI/Freund's, the nHgbAI/MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed. PMID- 20584975 TI - Transforming growth factor beta and CD25 are important for controlling systemic dissemination following Yersinia enterocolitica infection of the gut. AB - Infection of the gut by invasive bacterial pathogens leads to robust inflammatory responses that if left unchecked can lead to autoimmune disease and other sequelae. How the immune system controls inflammation and limits collateral damage to the host during acute bacterial infection is poorly understood. Here, we report that antibody-mediated neutralization of transforming growth factor beta (TGF-beta) prior to infection with the model enteric pathogen Yersinia enterocolitica reduces the mean time to death by 1 day (P=0.001), leads to rapid colonization of the liver and lung, and is associated with exacerbation of inflammatory histopathology. During Yersinia enterocolitica infection CD4+ cells are the source of de novo TGF-beta transcription in the Peyer's patches, mesenteric lymph nodes, and spleen. Correspondingly there is both antigen specific and -independent expansion of CD4+ CD25+ Foxp3+ and TGF-beta+ T regulatory cells (T-regs) after Yersinia infection that is reduced in ovalbumin T cell receptor-restricted OT-II mice. Functional inactivation of CD25 by anti-CD25 treatment results in more rapid death, dissemination of the bacteria to the liver and lungs, and exacerbated inflammatory histopathology, similar to what is seen during TGF-beta neutralization. Altogether, these data suggest that TGF-beta produced by T-regs is important in restricting bacteria during the acute phase of invasive bacterial infection of the gut. These data expand the roles of T-regs to include tempering inflammation during acute infection in addition to the well established roles of T-regs in chronic infection, control of immune homeostasis, and autoimmune disease. PMID- 20584976 TI - A pathoadaptive deletion in an enteroaggregative Escherichia coli outbreak strain enhances virulence in a Caenorhabditis elegans model. AB - Enteroaggregative Escherichia coli (EAEC) strains are important diarrheal pathogens. EAEC strains are defined by their characteristic stacked-brick pattern of adherence to epithelial cells but show heterogeneous virulence and have different combinations of adhesin and toxin genes. Pathoadaptive deletions in the lysine decarboxylase (cad) genes have been noted among hypervirulent E. coli subtypes of Shigella and enterohemorrhagic E. coli. To test the hypothesis that cad deletions might account for heterogeneity in EAEC virulence, we developed a Caenorhabditis elegans pathogenesis model. Well-characterized EAEC strains were shown to colonize and kill C. elegans, and differences in virulence could be measured quantitatively. Of 49 EAEC strains screened for lysine decarboxylase activity, 3 tested negative. Most notable is isolate 101-1, which was recovered in Japan, from the largest documented EAEC outbreak. EAEC strain 101-1 was unable to decarboxylate lysine in vitro due to deletions in cadA and cadC, which, respectively, encode lysine decarboxylase and a transcriptional activator of the cadAB genes. Strain 101-1 was significantly more lethal to C. elegans than control strain OP50. Lethality was attenuated when the lysine decarboxylase defect was complemented from a multicopy plasmid and in single copy. In addition, restoring lysine decarboxylase function produced derivatives of 101-1 deficient in aggregative adherence to cultured human epithelial cells. Lysine decarboxylase inactivation is pathoadapative in an important EAEC outbreak strain, and deletion of cad genes could produce hypervirulent EAEC lineages in the future. These results suggest that loss, as well as gain, of genetic material can account for heterogeneous virulence among EAEC strains. PMID- 20584977 TI - Porphyromonas gingivalis lipids inhibit osteoblastic differentiation and function. AB - Porphyromonas gingivalis produces unusual sphingolipids that are known to promote inflammatory reactions in gingival fibroblasts and Toll-like receptor 2 (TLR2) dependent secretion of interleukin-6 from dendritic cells. The aim of the present study was to examine whether P. gingivalis lipids inhibit osteoblastic function. Total lipids from P. gingivalis and two fractions, phosphoglycerol dihydroceramides and phosphoethanolamine dihydroceramides, were prepared free of lipid A. Primary calvarial osteoblast cultures derived from 5- to 7-day-old CD-1 mice were used to examine the effects of P. gingivalis lipids on mineralized nodule formation, cell viability, apoptosis, cell proliferation, and gene expression. P. gingivalis lipids inhibited osteoblast differentiation and fluorescence expression of pOBCol2.3GFP in a concentration-dependent manner. However, P. gingivalis lipids did not significantly alter osteoblast proliferation, viability, or apoptosis. When administered during specific intervals of osteoblast growth, P. gingivalis total lipids demonstrated inhibitory effects on osteoblast differentiation only after the proliferation stage of culture. Reverse transcription-PCR confirmed the downregulation of osteoblast marker genes, including Runx2, ALP, OC, BSP, OPG, and DMP-1, with concurrent upregulation of RANKL, tumor necrosis factor alpha, and MMP-3 genes. P. gingivalis total lipids and lipid fractions inhibited calvarial osteoblast gene expression and function in vivo, as determined by the loss of expression of another osteoblast differentiation reporter, pOBCol3.6GFPcyan, and reduced uptake of Alizarin complexone stain. Finally, lipid inhibition of mineral nodule formation in vitro was dependent on TLR2 expression. Our results indicate that inhibition of osteoblast function and gene expression by P. gingivalis lipids represents a novel mechanism for altering alveolar bone homeostasis at periodontal disease sites. PMID- 20584978 TI - Plasmodium vivax ookinete surface protein Pvs25 linked to cholera toxin B subunit induces potent transmission-blocking immunity by intranasal as well as subcutaneous immunization. AB - The nontoxic cholera toxin B subunit (CTB) was evaluated as a potential delivery molecule for the Plasmodium vivax ookinete surface protein, Pvs25. Recombinant Pvs25 was expressed as a secreted protein in the yeast Pichia pastoris, as a mixture of isoforms including multimers and the A and B monomers. The A isoform with the presumed native protein fold was the most abundant, accounting for more than 40% of all expressed protein. The molecularly uniform A isoform was chemically conjugated to CTB via its primary amines, and the fusion protein, retaining GM1-ganglioside affinity, was administered to BALB/c mice by the subcutaneous (s.c.) or intranasal (i.n.) route. Immunization of mice with conjugated Pvs25 without supplemental adjuvant induced antisera that specifically recognized P. vivax ookinetes in vitro. Furthermore, the antisera, when mixed with parasitized blood isolated from P. vivax patients from Thailand, was found to reduce parasite transmission to mosquitoes, conferring a 93 to 98% (s.c.) or a 73 to 88% (i.n.) decrease in oocyst number. Unconjugated Pvs25 alone conferred only a 23 to 60% (s.c.) or a 0 to 6% (i.n.) decrease in oocyst number. Coadministration of extraneous adjuvants, however, further enhanced the vaccine efficacy up to complete blockade. Taken together, we conclude that a weakly immunogenic Pvs25 by itself, when linked to CTB, transforms into a potent transmission-blocking antigen in both i.n. and s.c. routes. In addition, the present study is, to the best of our knowledge, the first demonstration of the immune potentiating function of CTB for a vaccine antigen delivered by the s.c. route. PMID- 20584979 TI - Phosphoinositide-dependent kinase 1 provides negative feedback inhibition to Toll like receptor-mediated NF-kappaB activation in macrophages. AB - Phosphoinositide-dependent kinase 1 (PDK-1) represents an important signaling component in the phosphatidylinositol 3-kinase (PI3K) pathway, which plays an essential role in controlling a coordinated innate immune response. Here, we show that mice with conditional disruption of PDK-1 specifically in myeloid lineage cells (PDK-1(Deltamyel) mice) show enhanced susceptibility to lipopolysaccharide (LPS)-induced septic shock accompanied by exaggerated liver failure. Furthermore, primary macrophages derived from PDK-1(Deltamyel) mice lack LPS- and Pam3CSK4 stimulated AKT activity but exhibit increased mRNA expression and release of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). Moreover, LPS- and Pam3CSK4-stimulated primary macrophages exhibit enhanced phosphorylation and degradation of IkappaBalpha. While immediate upstream Toll-like receptor 4 (TLR 4)-induced signaling, including IL-1 receptor (IL-1R)-associated protein kinase (IRAK) phosphorylation, is unaltered in the absence of PDK-1, macrophages from PDK-1(Deltamyel) mice exhibit prolonged ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF-6) in response to LPS stimulation. These experiments reveal a novel PDK-1-dependent negative feedback inhibition of TLR induced NF-kappaB activation in macrophages in vivo. PMID- 20584980 TI - CTCF controls expression and chromatin architecture of the human major histocompatibility complex class II locus. AB - The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divide the MHC-II locus into apparent evolutionary domains were identified. To define the role of CTCF in mediating regulation of the MHC II genes, chromatin conformation capture assays, which provide an architectural assessment of a locus, were conducted across the MHC-II region. Depending on whether MHC-II genes and the class II transactivator (CIITA) were being expressed, two CTCF-dependent chromatin architectural states, each with multiple configurations and interactions, were observed. These states included the ability to express MHC-II gene promoter regions to interact with nearby CTCF sites and CTCF sites to interact with each other. Thus, CTCF organizes the MHC-II locus into a novel basal architecture of interacting foci and loop structures that rearranges in the presence of CIITA. Disruption of the rearranged states eradicated expression, suggesting that the formation of these structures is key to coregulation of MHC II genes and the locus. PMID- 20584981 TI - Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis. AB - Both insulin and bone morphogenetic protein (BMP) signaling systems are important for adipocyte differentiation. Analysis of gene expression in BMP7-treated fibroblasts revealed a coordinated change in insulin signaling components by BMP7. To further investigate the cross talk between insulin and BMP signaling systems in brown adipogenesis, we examined the effect of BMP7 in insulin receptor substrate 1 (IRS-1)-deficient brown preadipocytes, which exhibit a severe defect in differentiation. Treatment of these cells with BMP7 for 3 days prior to adipogenic induction restored differentiation and expression of brown adipogenic markers. The high level of adipogenic inhibitor preadipocyte factor 1 (Pref-1) in IRS-1-null cells was markedly reduced by 3 days of BMP7 treatment, and analysis of the 1.3-kb pref-1 promoter revealed 9 putative Smad binding elements (SBEs), suggesting that BMP7 could directly suppress Pref-1 expression, thereby allowing the initiation of the adipogenic program. Using a series of sequential deletion mutants of the pref-1 promoter linked to the luciferase gene and chromatin immunoprecipitation, we demonstrate that the promoter-proximal SBE (-192/-184) was critical in mediating BMP7's suppressive effect on pref-1 transcription. Together, these data suggest cross talk between the insulin and BMP signaling systems by which BMP7 can rescue brown adipogenesis in cells with insulin resistance. PMID- 20584982 TI - Myristoylation and membrane binding regulate c-Src stability and kinase activity. AB - Myristoylation is critical for membrane association of Src kinases, but a role for myristate in regulating other aspects of Src biology has not been explored. In the c-Abl tyrosine kinase, myristate binds within a hydrophobic pocket at the base of the kinase domain and latches the protein into an autoinhibitory conformation. A similar pocket has been predicted to exist in c-Src, raising the possibility that Src might also be regulated by myristoylation. Here we show that in contrast to the case for c-Abl, myristoylation exerts a positive effect on c Src kinase activity. We also demonstrate that myristoylation and membrane binding regulate c-Src ubiquitination and degradation. Nonmyristoylated c-Src exhibited reduced kinase activity but had enhanced stability compared to myristoylated c Src. We then mutated critical residues in the predicted myristate binding pocket of c-Src. Mutation of L360 and/or E486 had no effect on c-Src membrane binding or localization. However, constructs containing a T456A mutation were partially released from the membrane, suggesting that mutagenesis could induce c-Src to undergo an artificial myristoyl switch. All of the pocket mutants exhibited decreased kinase activity. We concluded that myristoylation and the pocket residues regulate c-Src, but in a manner very different from that for c-Abl. PMID- 20584983 TI - Genes of the ecdysone biosynthesis pathway are regulated by the dATAC histone acetyltransferase complex in Drosophila. AB - Uncovering mechanisms that regulate ecdysone production is an important step toward understanding the regulation of insect metamorphosis and processes in steroid-related pathologies. We report here the transcriptome analysis of Drosophila melanogaster dAda2a and dAda3 mutants, in which subunits of the ATAC acetyltransferase complex are affected. In agreement with the fact that these mutations lead to lethality at the start of metamorphosis, both the ecdysone levels and the ecdysone receptor binding to polytene chromosomes are reduced in these flies. The cytochrome genes (spookier, phantom, disembodied, and shadow) involved in steroid conversion in the ring gland are downregulated, while the gene shade, which is involved in converting ecdysone into its active form in the periphery, is upregulated in these dATAC subunit mutants. Moreover, driven expression of dAda3 at the site of ecdysone synthesis partially rescues dAda3 mutants. Mutants of dAda2b, a subunit of the dSAGA histone acetyltransferase complex, do not share phenotype characteristics and RNA profile alterations with dAda2a mutants, indicating that the ecdysone biosynthesis genes are regulated by dATAC, but not by dSAGA. Thus, we provide one of the first examples of the coordinated regulation of a functionally linked set of genes by the metazoan specific ATAC complex. PMID- 20584984 TI - Islet beta-cell-specific MafA transcription requires the 5'-flanking conserved region 3 control domain. AB - MafA is a key transcriptional activator of islet beta cells, and its exclusive expression within beta cells of the developing and adult pancreas is distinct among pancreatic regulators. Region 3 (base pairs -8118 to -7750 relative to the transcription start site), one of six conserved 5' cis domains of the MafA promoter, is capable of directing beta-cell-line-selective expression. Transgenic reporters of region 3 alone (R3), sequences spanning regions 1 to 6 (R1-6; base pairs -10428 to +230), and R1-6 lacking R3 (R1-6(DeltaR3)) were generated. Only the R1-6 transgene was active in MafA(+) insulin(+) cells during development and in adult cells. R1-6 also mediated glucose-induced MafA expression. Conversely, pancreatic expression was not observed with the R3 or R1-6(DeltaR3) line, although much of the nonpancreatic expression pattern was shared between the R1-6 and R1-6(DeltaR3) lines. Further support for the importance of R3 was also shown, as the islet regulators Nkx6.1 and Pax6, but not NeuroD1, activated MafA in gel shift, chromatin immunoprecipitation (ChIP), and transfection assays and in vivo mouse knockout models. Lastly, ChIP demonstrated that Pax6 and Pdx-1 also bound to R1 and R6, potentially functioning in pancreatic and nonpancreatic expression. These data highlight the nature of the cis- and trans-acting factors controlling the beta-cell-specific expression of MafA. PMID- 20584985 TI - The C-terminal region of eukaryotic translation initiation factor 3a (eIF3a) promotes mRNA recruitment, scanning, and, together with eIF3j and the eIF3b RNA recognition motif, selection of AUG start codons. AB - The C-terminal domain (CTD) of the a/Tif32 subunit of budding yeast eukaryotic translation initiation factor 3 (eIF3) interacts with eIF3 subunits j/Hcr1 and b/Prt1 and can bind helices 16 to 18 of 18S rRNA, suggesting proximity to the mRNA entry channel of the 40S subunit. We have identified substitutions in the conserved Lys-Glu-Arg-Arg (KERR) motif and in residues of the nearby box6 element of the a/Tif32 CTD that impair mRNA recruitment by 43S preinitiation complexes (PICs) and confer phenotypes indicating defects in scanning and start codon recognition. The normally dispensable CTD of j/Hcr1 is required for its binding to a/Tif32 and to mitigate the growth defects of these a/Tif32 mutants, indicating physical and functional interactions between these two domains. The a/Tif32 CTD and the j/Hcr1 N-terminal domain (NTD) also interact with the RNA recognition motif (RRM) in b/Prt1, and mutations in both subunits that disrupt their interactions with the RRM increase leaky scanning of an AUG codon. These results, and our demonstration that the extreme CTD of a/Tif32 binds to Rps2 and Rps3, lead us to propose that the a/Tif32 CTD directly stabilizes 43S subunit mRNA interaction and that the b/Prt1-RRM-j/Hcr1-a/Tif32-CTD module binds near the mRNA entry channel and regulates the transition between scanning-conducive and initiation-competent conformations of the PIC. PMID- 20584986 TI - miR-375 inhibits differentiation of neurites by lowering HuD levels. AB - Neuronal development and plasticity are maintained by tightly regulated gene expression programs. Here, we report that the developmentally regulated microRNA miR-375 affects dendrite formation and maintenance. miR-375 overexpression in mouse hippocampus potently reduced dendrite density. We identified the predominantly neuronal RNA-binding protein HuD as a key effector of miR-375 influence on dendrite maintenance. Heterologous reporter analysis verified that miR-375 repressed HuD expression through a specific, evolutionarily conserved site on the HuD 3' untranslated region. miR-375 overexpression lowered both HuD mRNA stability and translation and recapitulated the effects of HuD silencing, which reduced the levels of target proteins with key functions in neuronal signaling and cytoskeleton organization (N-cadherin, PSD-95, RhoA, NCAM1, and integrin alpha1). Moreover, the increase in neurite outgrowth after brain-derived neurotrophic factor (BDNF) treatment was diminished by miR-375 overexpression; this effect was rescued by reexpression of miR-375-refractory HuD. Our findings indicate that miR-375 modulates neuronal HuD expression and function, in turn affecting dendrite abundance. PMID- 20584987 TI - Human Pat1b connects deadenylation with mRNA decapping and controls the assembly of processing bodies. AB - In eukaryotic cells, degradation of many mRNAs is initiated by removal of the poly(A) tail followed by decapping and 5'-3' exonucleolytic decay. Although the order of these events is well established, we are still lacking a mechanistic understanding of how deadenylation and decapping are linked. In this report we identify human Pat1b as a protein that is tightly associated with the Ccr4-Caf1 Not deadenylation complex as well as with the Dcp1-Dcp2 decapping complex. In addition, the RNA helicase Rck and Lsm1 proteins interact with human Pat1b. These interactions are mediated via at least three independent domains within Pat1b, suggesting that Pat1b serves as a scaffold protein. By tethering Pat1b to a reporter mRNA, we further provide evidence that Pat1b is also functionally linked to both deadenylation and decapping. Finally, we report that Pat1b strongly induces the formation of processing (P) bodies, cytoplasmic foci that contain most enzymes of the RNA decay machinery. An amino-terminal region within Pat1b serves as an aggregation-prone domain that nucleates P bodies, whereas an acidic domain controls the size of P bodies. Taken together, these findings provide evidence that human Pat1b is a central component of the RNA decay machinery by physically connecting deadenylation with decapping. PMID- 20584988 TI - Opposing roles of Dnmt1 in early- and late-stage murine prostate cancer. AB - Previous studies have shown that tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model is characterized by global DNA hypomethylation initiated during early-stage disease and locus-specific DNA hypermethylation occurring predominantly in late-stage disease. Here, we utilized Dnmt1 hypomorphic alleles to examine the role of Dnmt1 in normal prostate development and in prostate cancer in TRAMP. Prostate tissue morphology and differentiation status was normal in Dnmt1 hypomorphic mice, despite global DNA hypomethylation. TRAMP; Dnmt1 hypomorphic mice also displayed global DNA hypomethylation, but were characterized by altered tumor phenotype. Specifically, TRAMP; Dnmt1 hypomorphic mice exhibited slightly increased tumor incidence and significantly increased pathological progression at early ages and, conversely, displayed slightly decreased tumor incidence and significantly decreased pathological progression at advanced ages. Remarkably, hypomorphic Dnmt1 expression abrogated local and distant site macrometastases. Thus, Dnmt1 has tumor suppressor activity in early-stage prostate cancer, and oncogenic activity in late stage prostate cancer and metastasis. Consistent with the biological phenotype, epigenomic studies revealed that TRAMP; Dnmt1 hypomorphic mice show dramatically reduced CpG island and promoter DNA hypermethylation in late-stage primary tumors compared to control mice. Taken together, the data reveal a crucial role for Dnmt1 in prostate cancer and suggest that Dnmt1-targeted interventions may have utility specifically for advanced and/or metastatic prostate cancer. PMID- 20584989 TI - Dynamic localization of Fus3 mitogen-activated protein kinase is necessary to evoke appropriate responses and avoid cytotoxic effects. AB - Cellular responses to many external stimuli are mediated by mitogen-activated protein kinases (MAPKs). We investigated whether dynamic intracellular movement contributes to the spatial and temporal characteristics of the responses elicited by a prototypic MAPK, Fus3, in the mating pheromone response pathway in budding yeast (Saccharomyces cerevisiae). Confining Fus3 in the nucleus, via fusion to a histone H2B, reduced MAPK activation and diminished all responses (pheromone induced gene expression, cell cycle arrest, projection formation, and mating). Elimination of MAPK phosphatases restored more robust outputs for all responses, indicating that nuclear sequestration impedes full MAPK activation but does not abrogate its functional competence. Restricting Fus3 to the plasma membrane, via fusion to a lipid-modified CCaaX motif, led to MAPK hyperactivation yet severely impaired all response outputs. Fus3-CCaaX also caused aberrant cell morphology and a proliferation defect. Unlike similar phenotypes induced by pathway hyperactivation via upstream components, these deleterious effects were independent of the downstream transcription factor Ste12. Thus, appropriate cellular responses require free subcellular MAPK transit to disseminate MAPK activity optimally because preventing dynamic MAPK movement either markedly impaired signal-dependent activation and/or resulted in improper biological outputs. PMID- 20584991 TI - Isolation of sox9 duplicates in catfish: localization, differential expression pattern during gonadal development and recrudescence, and hCG-induced up regulation of sox9 in testicular slices. AB - In vertebrates, sox9 is a transcription factor that plays a crucial role in testicular development and chondrogenesis. Here, we report cloning of isoforms of sox9 (sox9a and sox9b) from air-breathing catfish Clarias gariepinus, which undergoes an annual reproductive cycle. Tissue distribution pattern showed differential expression of sox9 duplicates, wherein both forms were highly expressed in brain and gonads. Furthermore, we observed a dimorphic expression pattern of sox9a and sox9b in both adult and developing gonads using RT-PCR, indicating that sox9a retained its function in testis while sox9b might have a new role to play in ovary. Changes in sox9 mRNA levels using real-time quantitative PCR (qRT-PCR) during the seasonal reproductive cycle revealed that sox9a transcript in testis was abundant during testicular recrudescence (during spermatogenesis), and its expression significantly decreased during spawning and post-spawning phases. Furthermore, treatments of human chorionic gonadotropin and 11-ketotestosterone in vitro up-regulated sox9a mRNA levels in the testicular slices at 12 and 24 h time points, suggesting that gonadotropins might stimulate sox9 expression. These results suggest that sox9 might have a plausible role in the entrainment of the testicular cycle. In contrast, during the ovarian cycle, sox9b mRNA levels gradually declined from preparatory to post-spawning phases. Immunohistochemical (IHC) data showed that, in testis, sox9 is detectable in Sertoli and spermatogonial cell types except spermatid/spermatozoa. In the ovary, it is localized in the ooplasm of primary and pre-vitellogenic oocytes. These results were further confirmed by whole-mount IHC and qRT-PCR. PMID- 20584990 TI - Sortilin facilitates signaling of ciliary neurotrophic factor and related helical type 1 cytokines targeting the gp130/leukemia inhibitory factor receptor beta heterodimer. AB - Sortilin is a member of the Vps10p domain family of neuropeptide and neurotrophin binding neuronal receptors. The family members interact with and partly share a variety of ligands and partake in intracellular sorting and protein transport as well as in transmembrane signal transduction. Thus, sortilin mediates the transport of both neurotensin and nerve growth factor and interacts with their respective receptors to facilitate ligand-induced signaling. Here we report that ciliary neurotrophic factor (CNTF), and related ligands targeting the established CNTF receptor alpha, binds to sortilin with high affinity. We find that sortilin may have at least two functions: one is to provide rapid endocytosis and the removal of CNTF, something which is not provided by CNTF receptor alpha, and the other is to facilitate CNTF signaling through the gp130/leukemia inhibitory factor (LIF) receptor beta heterodimeric complex. Interestingly, the latter function is independent of both the CNTF receptor alpha and ligand binding to sortilin but appears to implicate a direct interaction with LIF receptor beta. Thus, sortilin facilitates the signaling of all helical type 1 cytokines, which engage the gp130/LIF receptor beta complex. PMID- 20584992 TI - Sperm DNA fragmentation induced by DNAse I and hydrogen peroxide: an in vitro comparative study among different mammalian species. AB - Sperm DNA damage may have adverse effects on reproductive outcome. Sperm DNA breaks can be detected by several tests, which evaluate DNA integrity from different and complementary perspectives and offer a new class of biomarkers of the male reproductive function and of its possible impairment after environmental exposure. The remodeling of sperm chromatin produces an extremely condensed nuclear structure protecting the nuclear genome from adverse environments. This nuclear remodeling is species specific, and differences in chromatin structure may lead to a dissimilar DNA susceptibility to mutagens among species. In this study, the capacity of the comet assay in its two variants (alkaline and neutral) to detect DNA/chromatin integrity has been evaluated in human, mouse, and bull sperm. The hypothesis that chromatin packaging might influence the amount of induced and detectable DNA damage was tested by treating sperm in vitro with DNAse I, whose activity is strictly dependent upon its DNA accessibility. Furthermore, hydrogen peroxide (H2O2) was used to assess whether spermatozoa of the three species showed a different sensitivity to oxidative stress. DNAse I induced damage was also assessed by the sperm chromatin structure assay and the TUNEL assay, and the performances of these two assays were compared and correlated with the comet assay results. Results showed a different sensitivity to DNAse I treatment among the species with human sperm resulting the most susceptible. On the contrary, no major differences among species were observed after H2O2 treatment. Furthermore, the three tests show a good correlation in revealing sperm with DNA strand breaks. PMID- 20584993 TI - Using MRI to measure drug action: caveats and new directions. AB - Investigating pharmacological modulation of brain activity using magnetic resonance imaging (MRI) presents an exciting opportunity to bridge the gap between preclinical and clinical studies, and holds the potential to be a useful tool in the discovery and development of novel therapeutic agents. Most functional MRI studies to date have utilized the blood oxygen level dependent (BOLD) contrast mechanism. Although this has some advantages over other techniques and is widely available, BOLD has two significant limitations for the study of drug effects; it is an indirect measurement of neuronal function, and produces only a relative (non-quantitative) measure of blood dynamics. Here we describe the various experimental manipulations that have been used to reduce the impact of these limitations, and discuss new ways of collecting and analysing imaging data that allow us to assess functional connectivity of the brain. We recommend some complementary techniques (such as arterial spin labelling and magnetoencephalography) that, if used in conjunction with BOLD functional MRI, will increase the interpretability and thus the utility of MRI for pharmacology research. PMID- 20584994 TI - Genetic moderation of CO2-induced fear by 5-HTTLPR genotype. AB - Inhalation of an increased concentration of carbon dioxide (CO(2)) has been shown to induce a state of negative affect in healthy subjects that is closely related to the clinical phenomenon of panic. It has been suggested that the vulnerability to CO(2) is moderated by differences in serotonin (5-HT) activity, caused by a functional polymorphism in the promoter region of the 5-HT transporter (5-HTTLPR) gene. Our aim was to examine the relationship between bi- and tri-allelic 5 HTTLPR genotype and the affective response to different dosages of inhaled CO(2) in healthy volunteers. Ninety-six subjects performed a double inhalation of four mixtures containing, respectively, 0%, 9%, 17.5% and 35% CO(2), following a double-blind, cross-over, randomized design. Affective responses were measured with a visual analogue scale for fear and the Panic Symptom List. 5-HTTLPR genotype was expressed as LL, SL and SS. Subjects with the SL and SS genotype reported less fear than LL subjects. A significant interaction effect was found between genotype and CO(2) dosage: the SS genotype showed lower fear scores than the LL genotype, particularly in the 17.5% CO(2) dose condition. The present study suggests that the dose-dependent fear reaction to CO(2) is moderated by a polymorphism in the 5-HT transporter gene, particularly at intermediate CO(2) dosages. It also underscores the usefulness of the introduction of an intermediate phenotype related to panic to reveal an underlying genetic vulnerability otherwise staying elusive. These results are in line with current theories on the role of 5-HT in both panic and respiration. PMID- 20584995 TI - Stem cells in human reproduction. PMID- 20584996 TI - Association of intramyocellular, intraperitoneal and liver fat with glucose tolerance in severely obese adolescents. AB - OBJECTIVE: Impaired glucose tolerance (IGT) is common among obese adolescents. The aim of the present study was to investigate the association between glucose tolerance and intramyocellular, intra-abdominal and liver fat in adolescents presenting with early-onset severe obesity. DESIGN AND METHODS: We studied 21 adolescents (mean age 13.5 years, range 11.5-15.9 years) referred to secondary care due to severe obesity (relative weight for height > +60% or body mass index > 98th percentile for age and sex, before the age of 10 years) and their eight non-obese siblings (mean age 14.4 years, range 11.8-16.7 years). All subjects underwent oral glucose tolerance tests, followed by magnetic resonance spectroscopy (MRS) to measure the intramyocellular fat content in mainly oxidative soleus and mainly glycolytic tibialis anterior muscles. MRS was also used to measure liver fat. Abdominal fat (subcutaneous, intraperitoneal and retroperitoneal) was measured using MR imaging. RESULTS: Compared with their non obese siblings, the obese adolescents had increased fat deposition in all anatomic locations studied. Eight obese adolescents had IGT, and they also had increased intramyocellular fat in the soleus (P=0.03) and increased intraperitoneal fat (P=0.04) compared with obese subjects with normal glucose tolerance (NGT). In contrast, no significant difference was seen between obese adolescents with NGT and IGT in liver fat (P=0.9) or intramyocellular fat in the tibialis anterior (P=0.13). In logistic regression analysis, increased soleus intramyocellular fat and intraperitoneal fat were significant predictors of IGT. CONCLUSIONS: IGT in obese adolescents is associated with increased intramyocellular and intraperitoneal fat rather than liver fat. PMID- 20584997 TI - Health insurance status and control of diabetes and coronary artery disease risk factors on enrollment into the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. AB - PURPOSE: The purpose of this study was to examine measures of chronic disease severity and treatment according to insurance status in a clinical trial setting. METHODS: Baseline insurance status of 776 patients with type 2 diabetes and stable coronary artery disease (CAD) enrolled in the United States in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was analyzed with regard to measures of metabolic and cardiovascular risk factor control. RESULTS: Compared with patients with private or public insurance, the uninsured were younger, more often female, and less often white non-Hispanic. Uninsured patients had the greatest burden of CAD. Patients with public insurance were treated with the greatest number of medications, had the greatest self reported functional status, and the lowest mean glycosylated hemoglobin and low density lipoprotein (LDL) cholesterol values. Overall, for 5 measured risk factor targets, the mean number above goal was 2.49 +/- 1.18. After adjustment for demographic and clinical variables, insurance status was not associated with a difference in risk factor control. CONCLUSIONS: In the BARI 2D trial, we did not observe a difference in baseline cardiovascular risk factor control according to insurance status. An important observation, however, was that risk factor control overall was suboptimal, which highlights the difficulty in treating type 2 diabetes and CAD irrespective of insurance status. PMID- 20584998 TI - Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. AB - OBJECTIVE: The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose stimulated insulin secretion in healthy subjects. RESEARCH DESIGN AND METHODS: Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. RESULTS: The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15 , and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). CONCLUSIONS: This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function. PMID- 20584999 TI - Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin. AB - OBJECTIVE: The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. RESEARCH DESIGN AND METHODS: Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3 deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. RESULTS: Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell derived C3, and not serum C3, is involved in the induction of diabetes in this model. CONCLUSIONS: The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement dependent. PMID- 20585001 TI - Renal hyperfiltration and arterial stiffness in humans with uncomplicated type 1 diabetes. AB - OBJECTIVE: We have reported that renal hyperfiltration is associated with endothelial dysfunction in early type 1 diabetes. However, the relationship between renal hyperfiltration and arterial stiffness is unknown. Accordingly, we measured arterial stiffness in type 1 diabetic subjects with hyperfiltering (n = 20) or normofiltering (n = 18). RESEARCH DESIGN AND METHODS: Augmentation index (AIx), aortic pulse wave velocity (PWV), renal hemodynamic function (inulin and paraaminohippurate clearances), and urinary and circulating plasma cGMP were measured in normoalbuminuric subjects with type 1 diabetes during clamped euglycemia (glucose 4-6 mmol/l) and hyperglycemia (glucose 9-11 mmol/l). RESULTS: During clamped euglycemia, hyperfiltering subjects (glomerular filtration rate >or=135 ml/min/1.73 m(2)) exhibited lower AIx values (-6.1 +/- 2.9 vs. 13.9 +/- 2.7%, P = 0.001) and higher cGMP levels in urine and plasma compared with normofiltering subjects. These differences were maintained during clamped hyperglycemia. As expected, renal hemodynamic responses to clamped hyperglycemia were exaggerated in normofilterers, but values for AIx remained unchanged. CONCLUSIONS: Renal hyperfiltration is associated with reduced arterial stiffness in subjects with uncomplicated type 1 diabetes. PMID- 20585000 TI - Sleep restriction for 1 week reduces insulin sensitivity in healthy men. AB - OBJECTIVE: Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness. RESEARCH DESIGN AND METHODS: This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20-35 years and BMI 20-30 kg/m(2)). Subjects spent 10 h/night in bed for >or=8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured. RESULTS: IVGTT-derived insulin sensitivity was reduced by (means +/- SD) 20 +/- 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 +/- 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 +/- 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep. CONCLUSIONS: Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance. PMID- 20585002 TI - Defining the ideal injection techniques when using 5-mm needles in children and adults. AB - OBJECTIVE: We aimed to establish the ideal injection techniques using 5-mm needles to reliably inject insulin into the subcutaneous fat in both children and adults and to quantify the associated pain and leakage of the test medium. RESEARCH DESIGN AND METHODS: A total of 259 subjects (122 children/adolescents and 137 adults) were injected with sterile air corresponding to 20 IU insulin (200 microl) with 32-G 5-mm needles at 90 degrees or 45 degrees , in the abdomen and thigh, and with or without a pinched skin fold. Injection depth was assessed via ultrasonography. Subjects rated pain on a visual analog scale. Test medium injections into the abdomen and thigh (0.2-0.6 ml) were also administered to assess injection leakage. RESULTS: Among children, 5.5% of injections were intramuscular (IM) and 0.5% were intradermal, while in adults, the incidence was 1.3 and 0.6%, respectively. The frequency of IM injections was greater in boys and negligible among adult women. Subcutaneous fat thickness was the primary predictor of the likelihood of IM injections (P < 0.001). A third of all patients reported experiencing no pain during insulin injection, with children/adolescents experiencing considerably more discomfort than adults. Some leakage of medium was observed, but was unrelated to injection volume and was generally minimal. CONCLUSIONS: 5-mm needles are reliably inserted into subcutaneous fat in both adults and children. These needles were associated with reduced pain and minimal leakage. We recommend an angled injection with a pinched skin fold for children, while in adults, the technique should be left to patient preference. PMID- 20585003 TI - Retinal blood flow in type 1 diabetic patients with no or mild diabetic retinopathy during euglycemic clamp. AB - OBJECTIVE: To compare total retinal blood flow in diabetic patients with no or mild nonproliferative diabetic retinopathy and healthy control subjects and to investigate in patients whether there is a difference between retinal blood flow before morning insulin and under normoglycemic conditions using a glucose clamp. RESEARCH DESIGN AND METHODS: Twenty patients with type 1 diabetes with no or mild diabetic retinopathy were included in this open parallel-group study, and 20 healthy age- and sex-matched subjects were included as control subjects. Retinal blood flow was assessed by combining velocity measurements using laser Doppler velocimetry and diameter measurements using a commercially available dynamic vessel analyzer. Measurements were performed before and during a euglycemic clamp. RESULTS: Total retinal blood flow was higher in diabetic patients (53 +/- 16 microl/min) than in healthy subjects (43 +/- 16 microl/min; P = 0.034 between groups). When plasma glucose in diabetic patients was reduced from 9.3 +/- 1.7 to 5.3 +/- 0.5 mmol/l (P < 0.001) retinal blood flow decreased to 49 +/- 15 microl/min (P = 0.0003 vs. baseline). Total retinal blood flow during the glucose clamp was not significantly different from blood flow in normal control subjects (P = 0.161). CONCLUSIONS: Type 1 diabetic patients with no or only mild diabetic retinopathy have increased retinal blood flow before their morning insulin dosage. Blood flow is reduced toward normal during euglycemic conditions. Retinal blood flow may fluctuate significantly with fluctuating plasma glucose levels, which may contribute to the microvascular changes seen in diabetic retinopathy. PMID- 20585004 TI - Prevalence of the metabolic syndrome among U.S. workers. AB - OBJECTIVE: Differences in the prevalence of cardiovascular disease (CVD) and its risk factors among occupational groups have been found in several studies. Certain types of workers (such as shift workers) may have a greater risk for metabolic syndrome, a precursor of CVD. The objective of this study was to assess the differences in prevalence and risk of metabolic syndrome among occupational groups using nationally representative data of U.S. workers. RESEARCH DESIGN AND METHODS: Data from 8,457 employed participants (representing 131 million U.S. adults) of the 1999-2004 National Health and Nutrition Examination Survey were used. Unadjusted and age-adjusted prevalence and simple and multiple logistic regression analyses were conducted, adjusting for several potential confounders (BMI, alcohol drinking, smoking, physical activity, and sociodemographic characteristics) and survey design. RESULTS: Of the workers, 20% met the criteria for the metabolic syndrome, with "miscellaneous food preparation and food service workers" and "farm operators, managers, and supervisors" having the greatest age adjusted prevalence (29.6-31.1%) and "writers, artists, entertainers, and athletes," and "engineers, architects, scientists" the lowest (8.5-9.2%). In logistic regression analyses "transportation/material moving" workers had significantly greater odds of meeting the criteria for metabolic syndrome relative to "executive, administrative, managerial" professionals (odds ratio 1.70 [95% CI 1.49-2.52]). CONCLUSIONS: There is variability in the prevalence of metabolic syndrome by occupational status, with "transportation/material moving" workers at greatest risk for metabolic syndrome. Workplace health promotion programs addressing risk factors for metabolic syndrome that target workers in occupations with the greatest odds may be an efficient way to reach at-risk populations. PMID- 20585005 TI - Effects of glutamine on glycemic control during and after exercise in adolescents with type 1 diabetes: a pilot study. AB - OBJECTIVE: To investigate if oral glutamine ameliorates exercise and postexercise nighttime hypoglycemia in type 1 diabetic adolescents. RESEARCH DESIGN AND METHODS: Ten adolescents (15.2 +/- 1.4 years [SD], A1C 6.9 +/- 0.9%) on insulin pumps were studied. The subjects were randomized to receive a glutamine or placebo drink pre-exercise and at bedtime (0.25 g/kg/dose). A 3:00 p.m. exercise session consisted of four 15-min treadmill/5-min rest cycles. Pre-exercise blood glucose was 140-150 mg/dl and was monitored throughout the night. Studies were randomized crossover over 3 weeks. RESULTS: Blood glucose levels dropped comparably (52%) during exercise on both days. However, the overnight number of hypoglycemic events was higher on glutamine than placebo (/=1 SD below the mean predicted HR or a chronotropic index <0.80 based on the prediction model established by this cohort were independent predictors of mortality (P<0.001 and P=0.023, respectively). CONCLUSIONS: Chronotropic incompetence is associated with an increased risk of death in asymptomatic women; however, the traditional male-based calculation overestimates the maximum HR for age in women. Sex-specific parameters of physiological HR response to exercise should be incorporated into clinical practice. PMID- 20585009 TI - Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation, left ventricular rupture, and adverse outcome in subacute myocardial infarction. AB - BACKGROUND: In patients with myocardial infarction, high serum levels of interleukin-6 cytokines predict a poor outcome. The common receptor of interleukin-6 cytokines, glycoprotein-130 (gp130), signals via janus kinase/signal transducer and activator of transcription (STAT), cytoplasmic protein tyrosine phosphatase/extracellular signal-regulated kinase, and phosphoinositide-3-kinase/Akt pathways, and the regulation of these pathways depends at least in part on the gp130 tyrosine-757 residue. By analyzing cardiomyocyte-specific gp130(Y757F) mutant mice, we investigated the effect of disturbed gp130 signaling after myocardial infarction. METHODS AND RESULTS: The cardiomyocyte-restricted alpha-myosin heavy chain-Cre-recombinase-loxP system was used to generate mice with gp130(Y757F) mutant cardiomyocytes (alphaMHC-Cre(tg/ );gp130(fl/Y757F) [Y(757)F]); all other cells carried at least 1 functional gp130 gene, ensuring normal gp130 signaling. Y(757)F mice displayed normal cardiac function and morphology at 3 months of age comparable to their nonmutant littermates. In response to myocardial infarction, Y(757)F mice displayed higher mortality associated with increased left ventricular rupture rate, sustained cardiac inflammation, and heart failure. These adverse effects were associated with prolonged and enhanced STAT3 activation and increased expression of interleukin-6 and of the complement-activating mannose-binding lectin C. Pharmacological inhibition of the complement system by cobra venom factor attenuated inflammation, prevented left ventricular rupture, and improved cardiac function in Y(757)F mice. Stronger effects were observed with a genetic reduction of STAT3 (STAT3(flox/+)) restricted to cardiomyocytes in Y(757)F mice, which prevented extensive upregulation of interleukin-6, complement activation, and sustained inflammation and lowered left ventricular rupture rate, heart failure, and mortality in subacute myocardial infarction. CONCLUSIONS: Impaired downregulation of gp130-mediated STAT3 activation in subacute infarction promotes cardiac inflammation, adverse remodeling, and heart failure, suggesting a potential causative role of high interleukin-6 serum levels after myocardial infarction. PMID- 20585010 TI - Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. AB - BACKGROUND: Diffuse myocardial fibrosis is a final end point in most cardiac diseases. It is missed by the cardiovascular magnetic resonance (CMR) late gadolinium enhancement technique. Currently, quantifying diffuse myocardial fibrosis requires invasive biopsy, with inherent risk and sampling error. We have developed a robust and noninvasive technique, equilibrium contrast CMR (EQ-CMR) to quantify diffuse fibrosis and have validated it against the current gold standard of surgical myocardial biopsy. METHODS AND RESULTS: The 3 principles of EQ-CMR are a bolus of extracellular gadolinium contrast followed by continuous infusion to achieve equilibrium; a blood sample to measure blood volume of distribution (1-hematocrit); and CMR to measure pre- and postequilibrium T1 (with heart rate correction). The myocardial volume of distribution is calculated, reflecting diffuse myocardial fibrosis. Clinical validation occurred in patients undergoing aortic valve replacement for aortic stenosis or myectomy in hypertrophic cardiomyopathy (n=18 and n=8, respectively). Surgical biopsies were analyzed for picrosirius red fibrosis quantification on histology. The mean histological fibrosis was 20.5+/-11% in aortic stenosis and 17.1+/-7.4% in hypertrophic cardiomyopathy. EQ-CMR correlated strongly with biopsy histological fibrosis: aortic stenosis, r(2)=0.86, Kendall Tau coefficient (T)=0.71, P<0.001; hypertrophic cardiomyopathy, r(2)=0.62, T=0.52, P=0.08; combined r(2)=0.80, T=0.67, P<0.001. CONCLUSIONS: We have developed and validated a new technique, EQ CMR, to measure diffuse myocardial fibrosis as an add-on to a standard CMR scan, which allows for the noninvasive quantification of the diffuse fibrosis burden in myocardial diseases. PMID- 20585011 TI - Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. AB - BACKGROUND: Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen associated pulmonary arterial hypertension in the modern management era. METHODS AND RESULTS: Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled. Patients were followed up for 3 years, and survival rates were analyzed. For incident cases, estimated survival (95% confidence intervals [CIs]) at 1, 2, and 3 years was 85.7% (95% CI, 76.5 to 94.9), 69.6% (95% CI, 57.6 to 81.6), and 54.9% (95% CI, 41.8 to 68.0), respectively. In a combined analysis population (incident patients and prevalent patients diagnosed within 3 years before study entry; n=190), 1-, 2-, and 3-year survival estimates were 82.9% (95% CI, 72.4 to 95.0), 67.1% (95% CI, 57.1 to 78.8), and 58.2% (95% CI, 49.0 to 69.3), respectively. Individual survival analysis identified the following as significantly and positively associated with survival: female gender, New York Heart Association functional class I/II, greater 6-minute walk distance, lower right atrial pressure, and higher cardiac output. Multivariable analysis showed that being female, having a greater 6-minute walk distance, and exhibiting higher cardiac output were jointly significantly associated with improved survival. CONCLUSIONS: In the modern management era, idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension remains a progressive, fatal disease. Mortality is most closely associated with male gender, right ventricular hemodynamic function, and exercise limitation. PMID- 20585012 TI - Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). AB - BACKGROUND: Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use. METHODS AND RESULTS: Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique. CONCLUSIONS: We identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID- 20585013 TI - Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. PMID- 20585014 TI - Responding to the clopidogrel warning by the US food and drug administration: real life is complicated. PMID- 20585015 TI - ACCF/AHA Clopidogrel clinical alert: approaches to the FDA "boxed warning": a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. PMID- 20585016 TI - Images in Cardiovascular Medicine. Inflammatory obstruction of the ureter caused by infrarenal aortitis. PMID- 20585017 TI - Letter by Protogerou et al regarding article, "Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease". PMID- 20585018 TI - Letter by Harris et al regarding article, "outcomes of patients with acute type a aortic intramural hematoma". PMID- 20585022 TI - Transformation of cardiovascular health: presidential address at the American Heart Association 2009 scientific sessions. PMID- 20585021 TI - Report of the pediatric heart network and national heart, lung, and blood institute working group on the perioperative management of congenital heart disease. PMID- 20585020 TI - Cardiovascular effects of ambient particulate air pollution exposure. PMID- 20585023 TI - Images in Cardiovascular Medicine. Cardiac magnetic resonance of acute myocarditis in an human immunodeficiency virus patient presenting with acute chest pain syndrome. PMID- 20585024 TI - Quantitative proteomics of caveolin-1-regulated proteins: characterization of polymerase i and transcript release factor/CAVIN-1 IN endothelial cells. AB - Caveolae are organelles abundant in the plasma membrane of many specialized cells including endothelial cells (ECs), epithelial cells, and adipocytes, and in these cells, caveolin-1 (Cav-1) is the major coat protein essential for the formation of caveolae. To identify proteins that require Cav-1 for stable incorporation into membrane raft domains, a quantitative proteomics analysis using isobaric tagging for relative and absolute quantification was performed on rafts isolated from wild-type and Cav-1-deficient mice. In three independent experiments, 117 proteins were consistently identified in membrane rafts with the largest differences in the levels of Cav-2 and in the caveola regulatory proteins Cavin-1 and Cavin-2. Because the lung is highly enriched in ECs, we validated and characterized the role of the newly described protein Cavin-1 in several cardiovascular tissues and in ECs. Cavin-1 was highly expressed in ECs lining blood vessels and in cultured ECs. Knockdown of Cavin-1 reduced the levels of Cav 1 and -2 and weakly influenced the formation of high molecular weight oligomers containing Cav-1 and -2. Cavin-1 silencing enhanced basal nitric oxide release from ECs but blocked proangiogenic phenotypes such as EC proliferation, migration, and morphogenesis in vitro. Thus, these data support an important role of Cavin-1 as a regulator of caveola function in ECs. PMID- 20585025 TI - Alterations of the salivary secretory peptidome profile in children affected by type 1 diabetes. AB - The acidic soluble fraction of whole saliva of type 1 diabetic children was analyzed by reversed phase (RP)(1)-HPLC-ESI-MS and compared with that of sex- and age-matched control subjects. Salivary acidic proline-rich phosphoproteins (aPRP), histatins, alpha-defensins, salivary cystatins, statherin, proline-rich peptide P-B (P-B), beta-thymosins, S100A8 and S100A9*(S100A9* corresponds to S100A9 vairant lacking the first four amino acids), as well some naturally occurring peptides derived from salivary acidic proline-rich phosphoproteins, histatins, statherin, and P-B peptide, were detected and quantified on the basis of the extracted ion current peak area. The level of phosphorylation of salivary acidic proline-rich phosphoproteins, histatin-1 (Hst-1), statherin and S100A9* and the percentage of truncated forms of salivary acidic proline-rich phosphoproteins was also determined in the two groups. The study revealed that statherin, proline-rich peptide P-B, P-C peptide, and histatins, were significantly less concentrated in saliva of diabetic subjects than in controls, while concentration of alpha-defensins 1, 2 and 4 and S100A9* was higher. The low concentration of P-C peptide was paralleled by high levels of some of its fragments. On the whole, the study highlighted the severe impairment of the repertoire of peptides involved in the safeguard of the oral cavity in children who have diabetes, as well as an higher concentration of the proinflammatory mediator S100A9* with respect to healthy children. PMID- 20585026 TI - Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. AB - Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g., inherited gain-of-function mutation channelopathies, ischemia, and chronic and vagally mediated atrial fibrillation). We hypothesize that the antimalarial quinoline chloroquine exerts potent antiarrhythmic effects by interacting with the cytoplasmic domains of Kir2.1 (I(K1)), Kir3.1 (I(KACh)), or Kir6.2 (I(KATP)) and reducing inward rectifier potassium currents. In isolated hearts of three different mammalian species, intracoronary chloroquine perfusion reduced fibrillatory frequency (atrial or ventricular), and effectively terminated the arrhythmia with resumption of sinus rhythm. In patch-clamp experiments chloroquine blocked I(K1), I(KACh), and I(KATP). Comparative molecular modeling and ligand docking of chloroquine in the intracellular domains of Kir2.1, Kir3.1, and Kir6.2 suggested that chloroquine blocks or reduces potassium flow by interacting with negatively charged amino acids facing the ion permeation vestibule of the channel in question. These results open a novel path toward discovering antiarrhythmic pharmacophores that target specific residues of the cytoplasmic domain of inward rectifier potassium channels. PMID- 20585027 TI - MR angiogenesis imaging with Robo4- vs. alphaVbeta3-targeted nanoparticles in a B16/F10 mouse melanoma model. AB - The primary objective of this study was to utilize MR molecular imaging to compare the 3-dimensional spatial distribution of Robo4 and alpha(V)beta(3) integrin as biosignatures of angiogenesis, in a rapidly growing, syngeneic tumor. B16-F10 melanoma-bearing mice were imaged with magnetic resonance (MR; 3.0 T) 11 d postimplantation before and after intravenous administration of either Robo4- or alpha(V)beta(3)-targeted paramagnetic nanoparticles. The percentage of MR signal-enhanced voxels throughout the tumor volume was low and increased in animals receiving alpha(V)beta(3)- and Robo4-targeted nanoparticles. Neovascular signal enhancement was predominantly associated with the tumor periphery (i.e., outer 50% of volume). Microscopic examination of tumors coexposed to the Robo4- and alpha(V)beta(3)-targeted nanoparticles corroborated the MR angiogenesis mapping results and further revealed that Robo4 expression generally colocalized with alpha(V)beta(3)-integrin. Robo4- and alpha(V)beta(3)-targeted nanoparticles were compared to irrelevant or nontargeted control groups in all modalities. These results suggest that alpha(V)beta(3)-integrin and Robo4 are useful biomarkers for noninvasive MR molecular imaging in syngeneic mouse tumors, but alpha(V)beta(3)-integrin expression was more detectable by MR at 3.0 T than Robo4. Noninvasive, neovascular assessments of the MR signal of Robo4, particularly combined with alpha(V)beta(3)-integrin expression, may help define tumor character prior to and following cancer therapy. PMID- 20585028 TI - c-Abl mediates high NaCl-induced phosphorylation and activation of the transcription factor TonEBP/OREBP. AB - The transcription factor TonEBP/OREBP promotes cell survival during osmotic stress. High NaCl-induced phosphorylation of TonEBP/OREBP at tyrosine-143 was known to be an important factor in increasing its activity in cell culture. We now find that TonEBP/OREBP also is phosphorylated at tyrosine-143 in rat renal inner medulla, dependent on the interstitial osmolality. c-Abl seemed likely to be the kinase that phosphorylates TonEBP/OREBP because Y143 is in a consensus c Abl phosphorylation site. We now confirm that, as follows. High NaCl increases c Abl activity. Specific inhibition of c-Abl by imatinib, siRNA, or c-Abl kinase dead drastically reduces high NaCl-induced TonEBP/OREBP activity by reducing its nuclear location and transactivating activity. c-Abl associates with TonEBP/OREBP (coimmunoprecipitation) and phosphorylates TonEBP/OREBP-Y143 both in cell and in vitro. High NaCl-induced activation of ataxia telangiectasia mutated, previously known to contribute to activation of TonEBP/OREBP, depends on c-Abl activity. Thus, c-Abl is the kinase responsible for high NaCl-induced phosphorylation of TonEBP/OREBP-Y143, which contributes to its increased activity. PMID- 20585029 TI - Group X secretory phospholipase A2 negatively regulates adipogenesis in murine models. AB - Studies in vitro indicate that group X secretory phospholipase A(2) (GX sPLA(2)) potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. To define the function of GX sPLA(2) in vivo, our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA(2) (GX(-/-) mice). When fed a normal rodent diet, GX(-/-) mice gained significantly more weight and had increased adiposity compared to GX(+/+) mice, which was not attributable to alterations in food consumption or energy expenditure. When treated with adipogenic stimuli ex vivo, stromal vascular cells isolated from adipose tissue of GX(-/-) mice accumulated significantly more (20%) triglyceride compared to cells from GX(+/+) mice. Conversely, overexpression of GX sPLA(2), but not catalytically inactive GX sPLA(2), resulted in a significant 50% reduction in triglyceride accumulation in OP9 adipocytes. The induction of genes encoding adipogenic proteins (PPARgamma, SREBP-1c, SCD1, and FAS) was also significantly blunted by 50-80% in OP9 cells overexpressing GX sPLA(2). Activation of the liver X receptor (LXR), a nuclear receptor known to up-regulate adipogenic gene expression, was suppressed in 3T3-L1 and OP9 cells when GX sPLA(2) was overexpressed. Thus, hydrolytic products generated by GX sPLA(2) negatively regulate adipogenesis, possibly by suppressing LXR activation. PMID- 20585030 TI - Modulation of Abeta42 fibrillogenesis by glycosaminoglycan structure. AB - The role of amyloid beta (Abeta) peptide in the onset and progression of Alzheimer's disease is linked to the presence of soluble Abeta species. Sulfated glycosaminoglycans (GAGs) promote Abeta fibrillogenesis and reduce the toxicity of the peptide in neuronal cell cultures, but a satisfactory rationale to explain these effects at the molecular level has not been provided yet. We have used circular dichroism, Fourier transform infrared spectroscopy, fluorescence microscopy and spectroscopy, protease digestion, atomic force microscopy (AFM), and molecular dynamics simulations to characterize the association of the 42 residue fragment Abeta(42) with sulfated GAGs, hyaluronan, chitosan, and poly(vinyl sulfate) (PVS). Our results indicate that the formation of stable Abeta(42) fibrils is promoted by polymeric GAGs with negative charges placed in frame with the 4.8-A separating Abeta(42) monomers within protofibrillar beta sheets. Incubation of Abeta(42) with excess sulfated GAGs and hyaluronan increased amyloid fibril content and resistance to proteolysis 2- to 5-fold, whereas in the presence of the cationic polysaccharide chitosan, Abeta(42) fibrillar species were reduced by 25% and sensitivity to protease degradation increased ~3-fold. Fibrils of intermediate stability were obtained in the presence of PVS, an anionic polymer with more tightly packed charges than GAGs. Important structural differences between Abeta(42) fibrils induced by PVS and Abeta(42) fibrils obtained in the presence of GAGs and hyaluronan were observed by AFM, whereas mainly precursor protofibrillar forms were detected after incubation with chitosan. Computed binding energies per peptide from -11.2 to 13.5 kcal/mol were calculated for GAGs and PVS, whereas a significantly lower value of -7.4 kcal/mol was obtained for chitosan. Taken together, our data suggest a simple and straightforward mechanism to explain the role of GAGs as enhancers of the formation of insoluble Abeta(42) fibrils trapping soluble toxic forms. PMID- 20585031 TI - Secretory-IgA antibodies play an important role in the immunity to Streptococcus pneumoniae. AB - This study was designed to investigate whether secretory-IgA (S-IgA) Abs induced by a pneumococcal surface protein A (PspA)-based nasal vaccine are necessary for prevention of streptococcal colonization. Mice nasally immunized with PspA plus a plasmid expressing Flt3 ligand (pFL) cDNA as a mucosal adjuvant showed significantly higher levels of PspA-specific S-IgA and IgG Ab responses in both plasma and nasal washes when compared with naive mice. Although IgA(-/-) mice given nasal PspA plus pFL had significantly high levels of PspA-specific IgG Abs, high numbers of CFUs were detected in nasal washes and nasal passages. In contrast, vaccinated wild-type mice showed essentially no bacteria in the nasal cavity. Further, a nasal vaccine consisting of PspA plus pFL effectively reduced pre-existing Streptococcus pneumoniae in the nasal cavity. These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity. PMID- 20585032 TI - Anti-CD40L immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A transgenic mice. AB - Anti-CD40L immunotherapy in systemic lupus erythematosus patients was associated with thromboembolism of unknown cause. We previously showed that monoclonal anti CD40L immune complexes (ICs) activated platelets in vitro via the IgG receptor (FcgammaRIIa). In this study, we examined the prothrombotic effects of anti-CD40L ICs in vivo. Because mouse platelets lack FcgammaRIIa, we used FCGR2A transgenic mice. FCGR2A mice were injected i.v. with preformed ICs consisting of either anti human CD40L mAb (M90) plus human CD40L, or a chimerized anti-mouse CD40L mAb (hMR1) plus mouse CD40L. ICs containing an aglycosylated form of hMR1, which does not bind FcgammaRIIa, were also injected. M90 IC caused shock and thrombocytopenia in FCGR2A but not in wild-type mice. Animals injected with hMR1 IC also experienced these effects, whereas those injected with aglycosylated-hMR1 IC did not, demonstrating that anti-CD40L IC-induced platelet activation in vivo is FcgammaRIIa-dependent. Sequential injections of individual IC components caused similar effects, suggesting that ICs were able to assemble in circulation. Analysis of IC-injected mice revealed pulmonary thrombi consisting of platelet aggregates and fibrin. Mice pretreated with a thrombin inhibitor became moderately thrombocytopenic in response to anti-CD40L ICs and had pulmonary platelet-thrombi devoid of fibrin. In conclusion, we have shown for the first time that anti-CD40L IC-induced thrombosis can be replicated in mice transgenic for FcgammaRIIa. This molecular mechanism may be important for understanding thrombosis associated with CD40L immunotherapy. The FCGR2A mouse model may also be useful for assessing the hemostatic safety of other therapeutic Abs. PMID- 20585033 TI - Cutting edge: CTNNBL1 is dispensable for Ig class switch recombination. AB - Ig class switch recombination (CSR) and somatic hypermutation require activation induced cytidine deaminase (AID). The search for AID-interaction factors has been a major research effort in the field, as the mechanism of preferential targeting of AID to Ig loci remains elusive. CTNNBL1 is one of the few identified AID interacting factors and has been shown to affect AID-mediated mutation and gene conversion in chicken DT40 cells. CTNNBL1 was also implicated in mammalian CSR by the fact that an AID mutant that fails to interact with CTNNBL1 also fails to support CSR in AID-deficient mouse B cells. To directly assess the role of CTNNBL1 in CSR, we disrupted the CTNNBL1 gene on both alleles in mouse CH12F3 cells by gene targeting. We found normal levels of CSR in CTNNBL1-deficient cells, indicating that CTNNBL1 is dispensable for CSR. PMID- 20585035 TI - Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus. AB - The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50-60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in the human population from 1930 to 2000, to induce cross-reactivity to and cross-protection against the pandemic swine-origin H1N1 virus, A/California/04/09. We show that exposure of mice to the 1947 virus, A/FM/1/47, or the 1934 virus, A/PR/8/34, induced robust cross-protective immune responses and these mice were protected against a lethal challenge with mouse adapted A/California/04/09 H1N1 virus. Conversely, we observed that mice exposed to the 2009 H1N1 virus were protected against a lethal challenge with mouse adapted 1947 or 1934 H1N1 viruses. In addition, exposure to the 2009 H1N1 virus induced broad cross-reactivity against H1N1 as well as H3N2 influenza viruses. Finally, we show that vaccination with the older H1N1 viruses, particularly A/FM/1/47, confers protective immunity against the 2009 pandemic H1N1 virus. Taken together, our data provide an explanation for the decreased susceptibility of the elderly to the 2009 H1N1 outbreak and demonstrate that vaccination with the pre-1950 influenza strains can cross-protect against the pandemic swine origin 2009 H1N1 influenza virus. PMID- 20585036 TI - A role for granzyme M in TLR4-driven inflammation and endotoxicosis. AB - Lymphocyte perforin and serine protease granzymes are well-recognized extrinsic mediators of apoptosis. We now demonstrate that cytotoxic lymphocyte granule components profoundly augment the myeloid cell inflammatory cytokine cascade in response to TLR4 ligation. Whereas caspase-1-deficient mice were completely resistant to LPS, reduced serum cytokine production and resistance to lethal endotoxicosis were also obtained with perforin-deficient mice, indicating a role for granzymes. Consistently, a lack of granzyme M (GrzM) resulted in reduced serum IL-1alpha, IL-1beta, TNF, and IFN-gamma levels and significantly reduced susceptibility to lethal endotoxicosis. These altered responses were also observed in granzyme A-deficient but not granzyme B-deficient mice. A role for APC-NK cell cross-talk in the inflammatory cascade was highlighted, as GrzM was exclusively expressed by NK cells and resistance to LPS was also observed on a RAG-1/GrzM-double deficient background. Collectively, the data suggest that NK cell GrzM augments the inflammatory cascade downstream of LPS-TLR4 signaling, which ultimately results in lethal endotoxicosis. Most importantly, these data demonstrate that granzymes should no longer be considered solely as mediators of apoptosis, but additionally as potential key regulators of inflammation. PMID- 20585034 TI - The cell-specific induction of CXC chemokine ligand 9 mediated by IFN-gamma in microglia of the central nervous system is determined by the myeloid transcription factor PU.1. AB - The IFN-gamma-inducible chemokines CXCL9 and CXCL10 are implicated in the pathogenesis of T cell-mediated immunity in the CNS. However, in various CNS immune pathologies the cellular localization of these chemokines differs, with CXCL9 produced by macrophage/microglia whereas CXCL10 is produced by both macrophage/microglia and astrocytes. In this study, we determined the mechanism for the microglial cell-restricted expression of the Cxcl9 gene induced by IFN gamma. In cultured glial cells, the induction of the CXCL9 (in microglia) and CXCL10 (in microglia and astrocytes) mRNAs by IFN-gamma was not inhibited by cycloheximide. Of various transcription factors involved with IFN-gamma-mediated gene regulation, PU.1 was identified as a constitutively expressed NF in microglia but not in astrocytes. STAT1 and PU.1 bound constitutively to the Cxcl9 gene promoter in microglia, and this increased significantly following IFN-gamma treatment with IFN regulatory factor-8 identified as an additional late binding factor. However, in astrocytes, STAT1 alone bound to the Cxcl9 gene promoter. STAT1 was critical for IFN-gamma induction of both the Cxcl9 and Cxcl10 genes in microglia and in microglia and astrocytes, respectively. The small interfering RNA-mediated knockdown of PU.1 in microglia markedly impaired IFN-gamma-induced CXCL9 but not STAT1 or IFN regulatory factor-8. Cells of the D1A astrocyte line showed partial reprogramming to a myeloid-like phenotype posttransduction with PU.1 and, in addition to the expression of CD11b, acquired the ability to produce CXCL9 in response to IFN-gamma. Thus, PU.1 not only is crucial for the induction of CXCL9 by IFN-gamma in microglia but also is a key determinant factor for the cell-specific expression of this chemokine by these myeloid cells. PMID- 20585037 TI - Role of the CXCR4/CXCL12 axis in lymphangioleiomyomatosis and angiomyolipoma. AB - Lymphangioleiomyomatosis (LAM) is a progressive disease caused by accumulation of metastatic (LAM) cells in the lungs, lymphatics, and the tumor angiomyolipoma (AML). LAM cells have biallelic loss of either tuberous sclerosis complex gene (but predominantly TSC-2) and resultant dysregulation of the mammalian target of rapamycin (mTOR) pathway. Chemokines are associated with neoplastic cell growth, survival, and homing to specific organs and may play similar roles in LAM. Our objective was to study comprehensively the expression and function of chemokine receptors and how their function interacts with dysregulation of the mTOR pathway in LAM and AML. We used RT-PCR and FACS to study receptor expression in primary AML cells and immunohistochemistry to investigate expression in tissues. Chemokine receptor function was analyzed in AML cells by Western blotting of signaling proteins and cell proliferation and apoptosis assays. Primary AML cells, LAM, and AML tissues expressed CCR3, CXCR4, CXCR6, and CXC3CR1. In AML cells, their ligands CXCL12 CX3CL1, CCL11, CCL24, and CCL28 caused robust phosphorylation of p42/44 MAPK and Akt. CXCL12 was expressed in type II pneumocytes covering LAM nodules and caused AML cell growth and protection from apoptosis, which was blocked by AMD3100, a CXCR4 inhibitor. The mTOR inhibitor rapamycin, but not AMD3100, inhibited growth of AML tumor xenografts. We conclude that the CXCL12/CXCR4 axis promotes, but is not absolutely required for, AML/LAM cell growth and survival. PMID- 20585038 TI - TCR beta allelic exclusion in dynamical models of V(D)J recombination based on allele independence. AB - Allelic exclusion represents a major aspect of TCRbeta gene assembly by V(D)J recombination in developing T lymphocytes. Despite recent progress, its comprehension remains problematic when confronted with experimental data. Existing models fall short in terms of incorporating into a unique distribution all the cell subsets emerging from the TCRbeta assembly process. To revise this issue, we propose dynamical, continuous-time Markov chain-based modeling whereby essential steps in the biological procedure (D-J and V-DJ rearrangements and feedback inhibition) evolve independently on the two TCRbeta alleles in every single cell while displaying random modes of initiation and duration. By selecting parameters via fitting procedures, we demonstrate the capacity of the model to offer accurate fractions of all distinct TCRbeta genotypes observed in studies using developing and mature T cells from wild-type or mutant mice. Selected parameters in turn afford relative duration for each given step, hence updating TCRbeta recombination distinctive timings. Overall, our dynamical modeling integrating allele independence and noise in recombination and feedback inhibition events illustrates how the combination of these ingredients alone may enforce allelic exclusion at the TCRbeta locus. PMID- 20585039 TI - Cooperation between deficiencies of IRF-4 and IRF-8 promotes both myeloid and lymphoid tumorigenesis. AB - Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF 4 and IRF-8 develop from a very early age a more aggressive chronic myelogenous leukemia-like disease than mice deficient in IRF-8 alone, correlating with a greater expansion of granulocyte-monocyte progenitors. Although these results demonstrate, for the first time, that IRF-4 can function as tumor suppressor in myeloid cells, interestingly, all mice deficient in both IRF-4 and IRF-8 eventually develop and die of a B-lymphoblastic leukemia/lymphoma. Combined losses of IRF-4 and IRF-8 therefore can cooperate in the development of both myeloid and lymphoid tumors. PMID- 20585040 TI - The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding. AB - Spectrin and protein 4.1R crosslink F-actin, forming the membrane skeleton. Actin and 4.1R bind to one end of beta-spectrin. The adjacent end of alpha-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium independent EF hands. The severely anemic sph(1J)/sph(1J) mouse has very fragile red cells and lacks the last 13 amino acids in the EF domain, implying that the domain is critical for skeletal integrity. To test this, we constructed a minispectrin heterodimer from the actin-binding domain, the EF domain, and 4 adjacent spectrin repeats in each chain. The minispectrin bound to F-actin in the presence of native human protein 4.1R. Formation of the spectrin-actin-4.1R complex was markedly attenuated when the minispectrin contained the shortened sph(1J) alpha-spectrin. The alpha-spectrin deletion did not interfere with spectrin heterodimer assembly or 4.1R binding but abolished the binary interaction between spectrin and F-actin. The data show that the alpha-spectrin EF domain greatly amplifies the function of the beta-spectrin actin-binding domain (ABD) in forming the spectrin-actin-4.1R complex. A model, based on the structure of alpha-actinin, suggests that the EF domain modulates the function of the ABD and that the C-terminal EF hands (EF(34)) may bind to the linker that connects the ABD to the first spectrin repeat. PMID- 20585041 TI - Tropomodulin 1-null mice have a mild spherocytic elliptocytosis with appearance of tropomodulin 3 in red blood cells and disruption of the membrane skeleton. AB - The short actin filaments in the red blood cell (RBC) membrane skeleton are capped at their pointed ends by tropomodulin 1 (Tmod1) and coated with tropomyosin (TM) along their length. Tmod1-TM control of actin filament length is hypothesized to regulate spectrin-actin lattice organization and membrane stability. We used a Tmod1 knockout mouse to investigate the in vivo role of Tmod1 in the RBC membrane skeleton. Western blots of Tmod1-null RBCs confirm the absence of Tmod1 and show the presence of Tmod3, which is normally not present in RBCs. Tmod3 is present at only one-fifth levels of Tmod1 present on wild-type membranes, but levels of actin, TMs, adducins, and other membrane skeleton proteins remain unchanged. Electron microscopy shows that actin filament lengths are more variable with spectrin-actin lattices displaying abnormally large and more variable pore sizes. Tmod1-null mice display a mild anemia with features resembling hereditary spherocytic elliptocytosis, including decreased RBC mean corpuscular volume, cellular dehydration, increased osmotic fragility, reduced deformability, and heterogeneity in osmotic ektacytometry. Insufficient capping of actin filaments by Tmod3 may allow greater actin dynamics at pointed ends, resulting in filament length redistribution, leading to irregular and attenuated spectrin-actin lattice connectivity, and concomitant RBC membrane instability. PMID- 20585042 TI - A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. AB - T-cell ubiquitin ligand-2 (TULA-2) is a recently discovered histidine tyrosine phosphatase thought to be ubiquitously expressed. In this work, we have investigated whether TULA-2 has a key role in platelet glycoprotein VI (GPVI) signaling. This study indicates that TULA-2 is expressed in human and murine platelets and is able to associate with Syk and dephosphorylate it. Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-gamma2 as well as enhanced GPVI-mediated platelet functional responses. In addition, shorter bleeding times and a prothrombotic phenotype were observed in mice lacking TULA-2. We therefore propose that TULA-2 is the primary tyrosine phosphatase mediating the dephosphorylation of Syk and thus functions as a negative regulator of GPVI signaling in platelets. PMID- 20585043 TI - Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera. AB - L3MBTL1, the human homolog of the Drosophila L(3)MBT polycomb group tumor suppressor gene, is located on chromosome 20q12, within the common deleted region identified in patients with 20q deletion-associated polycythemia vera, myelodysplastic syndrome, and acute myeloid leukemia. L3MBTL1 is expressed within hematopoietic CD34(+) cells; thus, it may contribute to the pathogenesis of these disorders. To define its role in hematopoiesis, we knocked down L3MBTL1 expression in primary hematopoietic stem/progenitor (ie, CD34(+)) cells isolated from human cord blood (using short hairpin RNAs) and observed an enhanced commitment to and acceleration of erythroid differentiation. Consistent with this effect, overexpression of L3MBTL1 in primary hematopoietic CD34(+) cells as well as in 20q- cell lines restricted erythroid differentiation. Furthermore, L3MBTL1 levels decrease during hemin-induced erythroid differentiation or erythropoietin exposure, suggesting a specific role for L3MBTL1 down-regulation in enforcing cell fate decisions toward the erythroid lineage. Indeed, L3MBTL1 knockdown enhanced the sensitivity of hematopoietic stem/progenitor cells to erythropoietin (Epo), with increased Epo-induced phosphorylation of STAT5, AKT, and MAPK as well as detectable phosphorylation in the absence of Epo. Our data suggest that haploinsufficiency of L3MBTL1 contributes to some (20q-) myeloproliferative neoplasms, especially polycythemia vera, by promoting erythroid differentiation. PMID- 20585044 TI - Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. AB - Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor-induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell-derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1(+)/c-Kit(+)/Lin(-) cells and interfered with their enhanced chemotactic migration to stromal cell-derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met-mediated mobilization. Our data show dynamic c Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms. PMID- 20585045 TI - Which dose of busulfan is best? PMID- 20585046 TI - Commentary. PMID- 20585047 TI - Commentary. PMID- 20585051 TI - Ameliorating children's reading-comprehension difficulties: a randomized controlled trial. AB - Children with specific reading-comprehension difficulties can read accurately, but they have poor comprehension. In a randomized controlled trial, we examined the efficacy of three interventions designed to improve such children's reading comprehension: text-comprehension (TC) training, oral-language (OL) training, and TC and OL training combined (COM). Children were assessed preintervention, midintervention, postintervention, and at an 11-month follow-up. All intervention groups made significant improvements in reading comprehension relative to an untreated control group. Although these gains were maintained at follow-up in the TC and COM groups, the OL group made greater gains than the other groups did between the end of the intervention and follow-up. The OL and COM groups also demonstrated significant improvements in expressive vocabulary compared with the control group, and this was a mediator of the improved reading comprehension of the OL and COM groups. We conclude that specific reading-comprehension difficulties reflect (at least partly) underlying oral-language weaknesses that can be effectively ameliorated by suitable teaching. PMID- 20585052 TI - Perceptual learning in a nonretinotopic frame of reference. AB - Perceptual learning is the ability to improve perception through practice. Perceptual learning is usually specific for the task and features learned. For example, improvements in performance for a certain stimulus do not transfer if the stimulus is rotated by 90 degrees or is presented at a different location. These findings are usually taken as evidence that orientation-specific, retinotopic encoding processes are changed during training. In this study, we used a novel masking paradigm in which the offset in an invisible, oblique vernier stimulus was perceived in an aligned vertical or horizontal flanking stimulus presented at a different location. Our results show that learning is specific for the perceived orientation of the vernier offset but not for its actual orientation and location. Specific encoding processes cannot be invoked to explain this improvement. We propose that perceptual learning involves changes in nonretinotopic, attentional readout processes. PMID- 20585053 TI - Restricted emigration, system inescapability, and defense of the status quo: system-justifying consequences of restricted exit opportunities. AB - The freedom to emigrate at will from a geographic location is an internationally recognized human right. However, this right is systematically violated by restrictive migration policies. In three experiments, we explored the psychological consequences of violating the right to mobility. Our results suggest that, ironically, restricted freedom of movement can lead to increased system justification (i.e., increased support of the status quo). In Study 1, we found that participants who read that their country was difficult to leave became stronger defenders of their system's legitimacy than before, even in domains unrelated to emigration policy (e.g., gender relations). In Study 2, we demonstrated that this increased system defense was the result of a motivated process. In Study 3, we broadened the scope of this psychological phenomenon by conceptually replicating it using a different system (participants' university) and measure of system defense. The importance of these two findings-the first experimental demonstration of the psychological consequences of restrictive emigration policies and the introduction of a novel psychological phenomenon-is discussed. PMID- 20585054 TI - Paracetamol/codeine probably had equivalent analgesia to ibuprofen in children with extremity injuries. PMID- 20585055 TI - Dosing dilemmas in obese children. AB - With the epidemic of childhood obesity, it is not uncommon for prescribers to puzzle over an appropriate drug dose for an obese child. Defining the optimum therapeutic dose of a drug relies on an understanding of pharmacokinetics and pharmacodynamics. Both these processes can be affected by body composition and the physiological changes that occur in obese children. As a rule of thumb, 75% of excess weight in obese subjects is fat mass, and the remainder lean mass. Although it is reasonable to assume that increases in fat mass alter the distribution of lipophilic drugs and increases in lean mass alter drug clearance, good quality and consistent clinical data supporting these assumptions are lacking for the majority of drugs. The relatively few clinical studies that have evaluated the impact of obesity have often been limited by poor design and insufficient sample size. Moreover, clinical studies conducted during drug development rarely include (or are required to include) obese subjects. Guidance on dosing obese children ought to be provided by drug manufacturers. This could be achieved by including obese patients in studies where possible, enabling the effect of body size on pharmacotherapy to be evaluated. This approach could be further augmented by the use of physiologically based-pharmacokinetic models during early (preclinical) development to predict the impact of obesity on drug disposition, and subsequent clinical studies later in development to provide confirmatory proof. In the meantime, for the majority of drugs already prescribed in children, particularly those where the therapeutic range is narrow or there is significant toxicity, the lack of a validated body size descriptor to use at the bedside means the choice of dose will rely on empirical experience and application of the precautionary principle. PMID- 20585056 TI - Spotting the wolf in sheep's clothing. PMID- 20585057 TI - Of trophies and pillars: exploring the terror management functions of short-term and long-term relationship partners. AB - Prior terror management research shows that mortality salience (MS) motivates both self-esteem striving and worldview bolstering. The present research examined these processes in the context of dating preferences. It was hypothesized that in short-term romantic contexts, MS-induced self-esteem striving motivates interest in dating a physically attractive other, whereas in long-term romantic contexts, MS-induced motives for worldview validation heighten interest in dating a same religion other. Study 1 showed that in a short-term dating context, MS increased preference for an attractive but religiously dissimilar person, whereas in a long term dating context, MS increased preference for a religiously similar, less attractive person. Study 2 clarified that MS motivates preference for attractive short-term partners for their self-enhancing properties rather than their potential sexual availability. Study 3 supported the theorized processes, showing that under MS, self-esteem-relevant constructs became spontaneously accessible in short-term dating contexts, whereas worldview-relevant constructs became spontaneously accessible in long-term dating contexts. PMID- 20585058 TI - The relation between trust beliefs and loneliness during early childhood, middle childhood, and adulthood. AB - Four studies examined the relation between trust and loneliness. Studies 1, 2, and 3 showed that trust beliefs negatively predicted changes in loneliness during early childhood (5-7 years), middle childhood (9-11 years), and young adulthood (18-21 years). Structural equation modeling yielded support for the hypothesis that the relation between trust beliefs and loneliness was mediated, in part, by social disengagement, which varied by age and gender. Study 4 showed that when young adults were primed for distrust rather than for trust cognitions, they showed greater withdrawal (loneliness) affect, lower willingness to disclose, and less perceived success in achieving rapport. The findings yielded support for the hypotheses that (a) low trust beliefs promote loneliness from childhood to adulthood and (b) social disengagement and cognitive schema mechanisms account for the relation. PMID- 20585059 TI - Relatedness of Vibrio cholerae O1/O139 isolates from patients and their household contacts, determined by multilocus variable-number tandem-repeat analysis. AB - The genetic relatedness of Vibrio cholerae O1/O139 isolates obtained from 100 patients and 146 of their household contacts in Dhaka, Bangladesh, between 2002 and 2005 was assessed by multilocus variable-number tandem-repeat analysis. Isolate genotypes were analyzed at five loci containing tandem repeats. Across the population, as well as within households, isolates with identical genotypes were clustered in time. Isolates from individuals within the same household were more likely to have similar or identical genotypes than were isolates from different households, but even within a household, isolates from different individuals often had different genotypes. When household contacts were sampled regularly for 3 weeks after the illness of the household index patient, isolates with genotypes related to the index patient appeared in contacts, on average, approximately 3 days after the index patient, while isolates with unrelated genotypes appeared in contacts approximately 6 days after. Limited data revealed that multiple isolates from the same individual collected within days of each other or even from a single stool sample may have identical, similar, or unrelated genotypes as well. Our results demonstrate that genetically related V. cholerae strains cluster in local outbreaks but also suggest that multiple distinct strains of V. cholerae O1 may circulate simultaneously within a household. PMID- 20585060 TI - Identification and characterization of a new ferric enterobactin receptor, CfrB, in Campylobacter. AB - The ferric enterobactin (FeEnt) receptor CfrA is present in the majority of Campylobacter jejuni isolates and is responsible for high-affinity iron acquisition. Our recent work and that of others strongly suggested the existence of another FeEnt uptake system in Campylobacter. Here we have identified and characterized a new FeEnt receptor (designated CfrB) using both in vitro and in vivo systems. CfrB, a homolog of C. jejuni NCTC 11168 Cj0444, shares approximately 34% of amino acid identity with CfrA. Alignment of complete CfrB sequences showed that the CfrB is highly conserved in Campylobacter. Immunoblotting analysis using CfrB-specific antiserum demonstrated that CfrB was dramatically induced under iron-restricted conditions and was produced in the majority of Campylobacter coli (41 out of 45) and in some C. jejuni (8 out of 32) primary strains from various sources and from geographically diverse areas. All of the CfrB-producing C. coli strains also produced CfrA, which was rarely observed in the tested C. jejuni strains. Isogenic cfrB, cfrA, and cfrA cfrB double mutants were constructed in 43 diverse Campylobacter strains. Growth promotion assays using these mutants demonstrated that CfrB has a major role in FeEnt iron acquisition in C. coli. Chicken colonization experiments indicated that inactivation of the cfrB gene alone greatly reduced and even abolished Campylobacter colonization of the intestines. A growth assay using CfrB-specific antiserum strongly suggested that specific CfrB antibodies could block the function of CfrB and diminish FeEnt-mediated growth promotion under iron restricted conditions. Together, this work reveals the complexity of FeEnt systems in the two closely related Campylobacter species and demonstrates the important role of the new FeEnt receptor CfrB in Campylobacter iron acquisition and in vivo colonization. PMID- 20585061 TI - Analyzing the regulatory role of the HigA antitoxin within Mycobacterium tuberculosis. AB - Bacterial chromosomally encoded type II toxin-antitoxin (TA) loci may be involved in survival upon exposure to stress and have been linked to persistence and dormancy. Therefore, understanding the role of the numerous predicted TA loci within the human pathogen Mycobacterium tuberculosis has become a topic of great interest. Antitoxin proteins are known to autoregulate TA expression under normal growth conditions, but it is unknown whether they have a more global role in transcriptional regulation. This study focuses on analyzing the regulatory role of the M. tuberculosis HigA antitoxin. We first show that the M. tuberculosis higBA locus is functional within its native organism, as higB, higA, and Rv1957 were successfully deleted from the genome together while the deletion of higA alone was not possible. The effects of higB-Rv1957 deletion on M. tuberculosis global gene expression were investigated, and a number of potential HigA regulated genes were identified. Transcriptional fusion and protein-DNA-binding assays were utilized to confirm the direct role of HigA in Rv1954A-Rv1957 repression, and the M. tuberculosis HigA DNA-binding motif was defined as ATATAGG(N(6))CCTATAT. As HigA failed to bind to the next-most-closely related motif within the M. tuberculosis genome, HigA may not directly regulate any other genes in addition to its own operon. PMID- 20585062 TI - Cholesterol-lowering therapy for primary prevention: still much we don't know. PMID- 20585063 TI - Prasugrel and cancer: an uncertain association or a credible risk that meaningfully alters the benefit-risk balance. PMID- 20585064 TI - When clinical practice guidelines meet the black box. PMID- 20585065 TI - Patient record review of the incidence, consequences, and causes of diagnostic adverse events. AB - BACKGROUND: Diagnostic errors often result in patient harm. Previous studies have shown that there is large variability in results in different medical specialties. The present study explored diagnostic adverse events (DAEs) across all medical specialties to determine their incidence and to gain insight into their causes and consequences by comparing them with other AE types. METHODS: A structured review study of 7926 patient records was conducted. Randomly selected records were reviewed by trained physicians in 21 hospitals across the Netherlands. The method used in this study was based on the well-known protocol developed by the Harvard Medical Practice Study. All AEs with diagnostic error as the main category were selected for analysis and were compared with other AE types. RESULTS: Diagnostic AEs occurred in 0.4% of hospital admissions and represented 6.4% of all AEs. Of the DAEs, 83.3% were judged to be preventable. Human failure was identified as the main cause (96.3%), although organizational- and patient-related factors also contributed (25.0% and 30.0%, respectively). The consequences of DAEs were more severe (higher mortality rate) than for other AEs (29.1% vs 7.4%). CONCLUSIONS: Diagnostic AEs represent an important error type, and the consequences of DAEs are severe. The causes of DAEs were mostly human, with the main causes being knowledge-based mistakes and information transfer problems. Prevention strategies should focus on training physicians and on the organization of knowledge and information transfer. PMID- 20585066 TI - Diagnostic adverse events: on to chapter 2: comment on "patient record review of the incidence, consequences, and causes of diagnostic adverse events". PMID- 20585067 TI - Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. AB - BACKGROUND: Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD. DATA SOURCES: Trials were identified through computerized literature searches of MEDLINE and Cochrane databases (January 1970-May 2009) using terms related to statins, clinical trials, and cardiovascular end points and through bibliographies of retrieved studies. STUDY SELECTION: Prospective, randomized controlled trials of statin therapy performed in individuals free from CVD at baseline and that reported details, or could supply data, on all-cause mortality. DATA EXTRACTION: Relevant data including the number of patients randomized, mean duration of follow-up, and the number of incident deaths were obtained from the principal publication or by correspondence with the investigators. DATA SYNTHESIS: Data were combined from 11 studies and effect estimates were pooled using a random-effects model meta-analysis, with heterogeneity assessed with the I(2) statistic. Data were available on 65,229 participants followed for approximately 244,000 person-years, during which 2793 deaths occurred. The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I(2) = 23%; 95% confidence interval, 0%-61% [P = .23]). CONCLUSION: This literature-based meta analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up. PMID- 20585068 TI - Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal. AB - BACKGROUND: Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels. METHODS: Careful review of both results and methods used in the trial and comparison with expected data. RESULTS: The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study. CONCLUSION: The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors. PMID- 20585069 TI - Variation in the net benefit of aggressive cardiovascular risk factor control across the US population of patients with diabetes mellitus. AB - BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in patients with diabetes mellitus (DM) can significantly reduce the risk of cardiovascular disease (CVD). However, to our knowledge, previous studies have not assessed variability in both the benefit and harm from pursuing LDL-C and BP target levels. METHODS: Our sample comprised individuals 30 to 75 years old with DM participating in the National Health and Nutrition Examination Survey III. We used Monte Carlo methods to simulate a treat-to-target strategy, in which patients underwent treatment intensification with the goal of achieving LDL-C and BP target levels of 100 mg/dL and 130/80 mm Hg, respectively. Patients received up to 5 titrations of statin therapy and 8 titrations of antihypertensive therapy. Treatment adverse effects and polypharmacy risks and burdens were incorporated using disutilities. Health outcomes were simulated using a Markov model. RESULTS: Treating to targets resulted in gains of 1.50 (for LDL-C) and 1.35 (for BP) quality-adjusted life-years (QALYs) of lifetime treatment-related benefit, which declined to 1.42 and 1.16 QALYs after accounting for treatment-related harms. Most of the total benefit was limited to the first few steps of medication intensification or to tight control for a limited group of very high-risk patients. However, because of treatment-related disutility, intensifying beyond the first step (LDL-C) or third step (BP) resulted in either limited benefit or net harm for patients with below-average risk. CONCLUSION: The benefits and harms from aggressive risk factor modification vary widely across the US population of individuals with DM, depending on a patient's underlying CVD risk, suggesting that a personalized approach could maximize a patient's net benefit from treatment. PMID- 20585070 TI - Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. AB - BACKGROUND: Trimethoprim therapy can cause hyperkalemia and is often coprescribed with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The objective of this study was to characterize the risk of hyperkalemia-associated hospitalization in elderly patients who were being treated with trimethoprim-sulfamethoxazole along with either an ACEI or an ARB. METHODS: We conducted a population-based, nested case-control study of a cohort of elderly patients 66 years or older who were residents of Ontario, Canada, and who were receiving continuous therapy with either an ACEI or an ARB. Case patients were those with a hyperkalemia-associated hospitalization within 14 days of receiving a prescription for trimethoprim-sulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. For each case, we identified up to 4 control patients from the same cohort matched for age, sex, and presence or absence of chronic renal disease and diabetes. Odds ratios were determined for the association between hyperkalemia-associated hospitalization and previous antibiotic use. RESULTS: During the 14-year study period, we identified 4148 admissions involving hyperkalemia, 371 of which occurred within 14 days of antibiotic exposure. Compared with amoxicillin, the use of trimethoprim sulfamethoxazole was associated with a nearly 7-fold increased risk of hyperkalemia-associated hospitalization (adjusted odds ratio, 6.7; 95% confidence interval, 4.5-10.0). No such risk was found with the use of comparator antibiotics. CONCLUSIONS: Among older patients treated with ACEIs or ARBs, the use of trimethoprim-sulfamethoxazole is associated with a major increase in the risk of hyperkalemia-associated hospitalization relative to other antibiotics. Alternate antibiotic therapy should be considered in these patients when clinically appropriate. PMID- 20585071 TI - Bicycle riding, walking, and weight gain in premenopausal women. AB - BACKGROUND: To our knowledge, research has not been conducted on bicycle riding and weight control in comparison with walking. Our objective was to assess the association between bicycle riding and weight control in premenopausal women. METHODS: This was a 16-year follow-up study of 18,414 women in the Nurses' Health Study II. Weight change between 1989 and 2005 was the primary outcome, and the odds of gaining more than 5% of baseline body weight by 2005 was the secondary outcome. RESULTS: At baseline, only 39% of participants walked briskly, while only 1.2% bicycled for more than 30 min/d. For a 30-min/d increase in activity between 1989 and 2005, weight gain was significantly less for brisk walking ( 1.81 kg; 95% confidence interval [CI], -2.05 to -1.56 kg), bicycling (-1.59 kg; 95% CI, -2.09 to -1.08 kg), and other activities (-1.45 kg; 95% CI, -1.66 to 1.24 kg) but not for slow walking (+0.06 kg; 95% CI, -0.22 to 0.35 kg). Women who reported no bicycling in 1989 and increased to as little as 5 min/d in 2005 gained less weight (-0.74 kg; 95% CI, -1.41 to -0.07 kg; P value for trend, <.01) than those who remained nonbikers. Normal-weight women who bicycled more than 4 h/wk in 2005 had a lower odds of gaining more than 5% of their baseline body weight (odds ratio, 0.74; 95% CI, 0.56 to 0.98) compared with those who reported no bicycling; overweight and obese women had a lower odds at 2 to 3 h/wk (odds ratio, 0.54; 95% CI, 0.34 to 0.86). CONCLUSIONS: Bicycling, similar to brisk walking, is associated with less weight gain and an inverse dose-response relationship exists, especially among overweight and obese women. Future research should focus on brisk walking and greater time spent bicycling. PMID- 20585072 TI - The quality of care provided to hospitalized patients at the end of life. AB - BACKGROUND: Patients in American hospitals receive intensive medical treatments. However, when lifesaving treatments are unsuccessful, patients often die in the hospital with distressing symptoms while receiving burdensome care. Systematic measurement of the quality of care planning and symptom palliation is needed. METHODS: Medical records were abstracted using 16 Assessing Care of Vulnerable Elders quality indicators within the domains of end-of-life care and pain management designed to measure the quality of the dying experience for adult decedents (n = 496) hospitalized for at least 3 days between April 2005 and April 2006 at a university medical center recognized for providing intensive care for the seriously ill. RESULTS: Over half of the patients (mean age, 62 years; 47% were women) were admitted to the hospital with end-stage disease, and 28% were 75 years or older. One-third of the patients required extubation from mechanical ventilation prior to death, and 15% died while receiving cardiopulmonary resuscitation. Overall, patients received recommended care for 70% of applicable indicators (range, 25%-100%). Goals of care were addressed in a timely fashion for patients admitted to the intensive care unit approximately half of the time, whereas pain assessments (94%) and treatments for pain (95%) and dyspnea (87%) were performed with fidelity. Follow-up for distressing symptoms was performed less well than initial assessment, and 29% of patients extubated in anticipation of death had documented dyspnea assessments. CONCLUSION: A practical, medical chart-based assessment identified discrete deficiencies in care planning and symptom palliation that can be targeted to improve care for patients dying in the hospital. PMID- 20585073 TI - Influence of physicians' management and communication ability on patients' persistence with antihypertensive medication. AB - BACKGROUND: Less than 75% of people prescribed antihypertensive medication are still using treatment after 6 months. Physicians determine treatment, educate patients, manage side effects, and influence patient knowledge and motivation. Although physician communication ability likely influences persistence, little is known about the importance of medical management skills, even though these abilities can be enhanced through educational and practice interventions. The purpose of this study was to determine whether a physician's medical management and communication ability influence persistence with antihypertensive treatment. METHODS: This was a population-based study of 13,205 hypertensive patients who started antihypertensive medication prescribed by a cohort of 645 physicians entering practice in Quebec, Canada, between 1993 and 2007. Medical Council of Canada licensing examination scores were used to assess medical management and communication ability. Population-based prescription and medical services databases were used to assess starting therapy, treatment changes, comorbidity, and persistence with antihypertensive treatment in the first 6 months. RESULTS: Within 6 months after starting treatment, 2926 patients (22.2%) had discontinued all antihypertensive medication. The risk of nonpersistence was reduced for patients who were treated by physicians with better medical management (odds ratio per 2-SD increase in score, 0.74; 95% confidence interval, 0.63-0.87) and communication (0.88; 0.78-1.00) ability and with early therapy changes (odds ratio, 0.45; 95% confidence interval, 0.37-0.54), more follow-up visits, and nondiuretics as the initial choice of therapy. Medical management ability was responsible for preventing 15.8% (95% confidence interval, 7.5%-23.3%) of nonpersistence. CONCLUSION: Better clinical decision-making and data collection skills and early modifications in therapy improve persistence with antihypertensive therapy. PMID- 20585074 TI - By Jove! What is a clinician to make of JUPITER? PMID- 20585076 TI - Prasugrel as a potential cancer promoter: review of the unpublished data. PMID- 20585077 TI - Physicians' views on defensive medicine: a national survey. PMID- 20585078 TI - Invited commentary--it is time to address the costs of defensive medicine: comment on "physicians' views on defensive medicine: a national survey". PMID- 20585079 TI - Increasing a patient's ability to identify his or her attending physician using a patient room display. PMID- 20585080 TI - Reasons for discontinuation of medication during hospitalization and documentation thereof: a descriptive study of 400 geriatric and internal medicine patients. PMID- 20585081 TI - Appropriate discard of "best" practice guidelines for acute low back pain. PMID- 20585082 TI - A possible epigenetic explanation for the relationship between physical activity and exceptional health among older women. PMID- 20585083 TI - Patient-centric colorectal cancer screening improvement strategies. PMID- 20585084 TI - Prolonged stability of progressive multifocal leukoencephalopathy in a patient with chronic lymphocytic leukemia. PMID- 20585086 TI - Role of cetuximab in the treatment of patients with NSCLC: are we throwing out the baby with the bath water? PMID- 20585089 TI - Impact of a pre-emptive skin treatment regimen on skin toxicities of anti epidermal growth factor receptor monoclonal antibodies: more questions than answers. PMID- 20585092 TI - Primary primitive neuroectodermal tumor of the breast. PMID- 20585090 TI - Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. AB - PURPOSE: While studies have found that adjuvant hormonal therapy for hormone sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. PATIENTS AND METHODS: We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio < 80%) of hormonal therapy. RESULTS: We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. CONCLUSION: Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women. PMID- 20585093 TI - Conflicting finding on intramucosal colon cancers based on national survival outcomes data. PMID- 20585094 TI - Rapid-learning system for cancer care. AB - Compelling public interest is propelling national efforts to advance the evidence base for cancer treatment and control measures and to transform the way in which evidence is aggregated and applied. Substantial investments in health information technology, comparative effectiveness research, health care quality and value, and personalized medicine support these efforts and have resulted in considerable progress to date. An emerging initiative, and one that integrates these converging approaches to improving health care, is "rapid-learning health care." In this framework, routinely collected real-time clinical data drive the process of scientific discovery, which becomes a natural outgrowth of patient care. To better understand the state of the rapid-learning health care model and its potential implications for oncology, the National Cancer Policy Forum of the Institute of Medicine held a workshop entitled "A Foundation for Evidence-Driven Practice: A Rapid-Learning System for Cancer Care" in October 2009. Participants examined the elements of a rapid-learning system for cancer, including registries and databases, emerging information technology, patient-centered and -driven clinical decision support, patient engagement, culture change, clinical practice guidelines, point-of-care needs in clinical oncology, and federal policy issues and implications. This Special Article reviews the activities of the workshop and sets the stage to move from vision to action. PMID- 20585095 TI - Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. AB - PURPOSE: Human T-cell lymphotropic virus type-I-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-alpha) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined. PATIENTS AND METHODS: We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed. RESULTS: According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021). CONCLUSION: These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL. PMID- 20585096 TI - Bevacizumab-induced diffusion restriction in patients with glioma: tumor progression or surrogate marker of hypoxia? PMID- 20585098 TI - Immunologic systemic effect of neoadjuvant chemotherapy requires investigation before tumor-associated lymphocytes can be introduced in breast cancer treatment algorithm. PMID- 20585099 TI - Impact of short-course preoperative radiotherapy for rectal cancer on patients' quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. AB - PURPOSE: The Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 (MRC CR07/NCIC CTG C016) trial showed that, in patients with operable rectal cancer, short-course preoperative radiotherapy (PRE) reduced the rate of local recurrence compared with surgery followed by selective postoperative chemoradiotherapy for patients with a positive circumferential resection margin. However, the advantages of giving PRE to all patients needs to be balanced against any negative impact on patients' quality of life. PATIENTS AND METHODS: All 1,350 patients were asked to complete the Medical Outcomes Study Short-Form 36-item (MOS SF-36) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal 38-item (EORTC QLQ-CR38) questionnaires. A priori hypotheses related to the impact of treatment on sexual, bowel, and physical function and general health. RESULTS: Male sexual dysfunction was significantly increased following surgery (P < .001), although there was no difference between treatment arms. However, a treatment difference had emerged at 6 months (PRE patients reporting significantly greater dysfunction; P = .004), which persisted out to at least 2 years (an insufficient number of female patients completed the sexual dysfunction questions to draw firm conclusions). Both treatment groups reported similar levels of decreased physical function at 3 months, but thereafter it returned to baseline levels. There was no evidence of any major changes between treatments or time points in terms of general health or bowel function, but exploratory analysis indicated a significant (P = .006 at 2 years) increase in the level of fecal incontinence with PRE. CONCLUSION: These results from a large randomized trial using validated patient-completed questionnaires show that, for males, the main adverse effect was sexual dysfunction, and the main cause of this was surgery, but that PRE also affected sexual and some aspects of bowel functioning. PMID- 20585101 TI - The effect of therapeutic touch on postoperative patients. AB - BACKGROUND: Therapeutic Touch (TT) is a complementary modality that has been demonstrated to reduce psychological distress and help patients to relax. It is unclear if there is an impact of TT on biobehavioral markers such as cortisol and natural killer cells (NKCs). There is some preliminary evidence that suggests relaxation may have positive effects on the immune system. PURPOSE: To test the efficacy of TT on pain and biobehavioral markers in patients recovering from vascular surgery. FRAMEWORK: The study was grounded in a psychoneuroimmunology framework to address how complementary therapies affect pain and biobehavioral markers associated with recovery in surgical patients. DESIGN: This was a between subjects intervention study. SAMPLE: Twenty-one postoperative surgical patients. MEASURES: Measures of level of pain and levels of cortisol and NKCs were obtained before and after a TT treatment. RESULTS: Compared with those who received usual care, participants who received TT had significantly lower level of pain, lower cortisol level, and higher NKC level. CONCLUSIONS AND IMPLICATIONS: Evidence supports TT as a beneficial intervention with patients. Future research on TT is still needed to learn more about how it functions. However, there is evidence to support incorporating TT into nursing practice. PMID- 20585102 TI - A study of the feasibility of introducing therapeutic touch into the operative environment with patients undergoing cerebral angiography. AB - The purpose of this pilot study was to determine whether Therapeutic Touch (TT) can be effectively used in the operative setting and whether it could produce positive outcomes in the period from cerebral angiography to discharge. The specific outcomes to be assessed were blood pressure, pulse, and respirations. TT is an intervention that involves the intentional direction of energy for the purpose of healing. The present study was developed within the conceptual framework of Rogers's model of unitary human beings. Data were collected at a center for endovascular surgery. The participants were 40 men and women aged between 18 and 80 years who were referred to the center for cerebral angiograms. The participants were English-speaking, ambulatory patients, with no history of prior cerebral angiograms and no psychiatric diagnosis. The design was a randomized, single-blind experiment. The research data were collected in the normal course of the angiogram procedure and recovery room. The blood pressure, pulse, and respirations were routinely noted before, during, and after the procedure. The study was significant in three aspects: (a) it was the first study to develop a protocol for delivering TT in the preoperative course of neurological patients, (b) the study is conceptualized within Rogers's conceptual model of unitary human beings, and (c) the study explored the impact of TT on selected outcomes in endovascular patients. A protocol for delivering TT in the operative setting was successfully developed and implemented. The efficacy of TT on the blood pressure, respirations, and pulse of the experimental group was not statistically significant. The reasons for this finding are explored, and suggestions are made for future research. PMID- 20585103 TI - Nursing 1000: a mosaic of lessons learned from patients. AB - Throughout my nursing career, I have been most grateful for the education and lessons that I received from the many gifted women and men faculty in the nursing programs I attended. From learning how to give a bed bath and intramuscular injections to writing a doctoral research proposal, the information, wisdom, guidance, and resources they shared with me are invaluable. I also am fortunate to have had the privilege of caring for many patients from whom I also learned invaluable lessons. Together, this latter group of women and men formed the faculty of Nursing 1000. They are the patients who were instrumental in shaping me and my nursing career. Many of them are no longer alive, and all of our paths have diverged, yet they remain influential in how I work with patients on a daily basis. The lessons they taught me form a most special montage. This mosaic article is a way to share with others what the faculty of Nursing 1000 taught me. It is also, in a small way, a tribute to all of the unique men and women with whom, as a nurse, I have shared transpersonal caring experiences and from whom I have learned much. The faculty of Nursing 1000 is composed of a variety of patients for whom I cared and who taught me valuable lessons that guided me in how to better care for patients in the future. Although the Nursing 1000 faculty are no longer physically part of my life, each day they continue to influence how I interact with others. The lessons they taught form a very special mosaic. To protect their confidentiality, all patient names are pseudonyms. PMID- 20585100 TI - Genome-wide association studies of cancer. AB - Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID- 20585104 TI - Expert holistic nurses' advice to nursing students. AB - PURPOSE: The purposes of this study were to describe the advice that expert holistic nurses gave to nursing students regarding the theory and practice of holistic nursing and to describe nursing students' experience and perceptions of their interaction with the experts. DESIGN: This was a qualitative descriptive study. METHODS: Nursing students who attended the 2008 and 2009 conferences of the American Holistic Nurses Association interviewed expert holistic nurses, asking them for advice for beginners. Students recorded the interviews on paper and wrote their perceptions of interacting with experts. The data were examined for recurring themes. FINDINGS: The most common advice from the experts was regarding the importance of self-care, person-centered care, touch, and lifelong learning. Students' perceptions of the interviews included feeling empowered to accomplish goals, gaining a greater understanding of holistic nursing, and feeling admiration for the holistic nurse experts. CONCLUSION: Giving students the opportunity to interact with nurse experts in an individual, informal setting is a useful educational strategy that increases knowledge, promotes socialization to the nursing profession, and offers students opportunities for professional networking. PMID- 20585106 TI - Effect of modest salt reduction on skin capillary rarefaction in white, black, and Asian individuals with mild hypertension. AB - Microvascular rarefaction occurs in hypertension. We carried out a 12-week randomized double-blind crossover trial to determine the effect of a modest reduction in salt intake on capillary rarefaction in 71 whites, 69 blacks, and 29 Asians with untreated mildly raised blood pressure. Both basal and maximal (during venous congestion) skin capillary density were measured by capillaroscopy at the dorsum and the side of the fingers. In addition, we used orthogonal polarization spectral imaging to measure skin capillary density at the dorsum of the fingers and the hand web. With a reduction in salt intake from 9.7 to 6.5 g/day, there was an increase in capillary density (capillaries per millimeter squared) from 101+/-21 to 106+/-23 (basal) and 108+/-22 to 115+/-22 (maximal) at the dorsum, and 101+/-25 to 107+/-26 (basal) and 110+/-26 to 116+/-26 (maximal) at the side of the fingers (P<0.001 for all). Orthogonal polarization spectral imaging also showed a significant increase in capillary density both at the dorsum of the fingers and the web. Subgroup analysis showed that most of the changes were significant in all of the ethnic groups. Furthermore, there was a significant relationship between the change in 24-hour urinary sodium and the change in capillary density at the side of the fingers. These results demonstrate that a modest reduction in salt intake, as currently recommended, improves both functional and structural capillary rarefactions that occur in hypertension, and a larger reduction in salt intake would have a greater effect. The increase in capillary density may possibly carry additional beneficial effects on target organs. PMID- 20585107 TI - Meta-analysis of genome-wide gene expression differences in onset and maintenance phases of genetic hypertension. AB - Gene expression differences accompany both the onset and established phases of hypertension. By an integrated genome-transcriptome approach we performed a meta analysis of data from 74 microarray experiments available on public databases to identify genes with altered expression in the kidney, adrenal, heart, and artery of spontaneously hypertensive and Lyon hypertensive rats. To identify genes responsible for the onset of hypertension we used a statistical approach that sought to eliminate expression differences that occur during maturation unrelated to hypertension. Based on this adjusted fold-difference statistic, we found 36 genes for which the expression differed between the prehypertensive phase and established hypertension. Genes having possible relevance to hypertension onset included Actn2, Ankrd1, ApoE, Cd36, Csrp3, Me1, Myl3, Nppa, Nppb, Pln, Postn, Spp1, Slc21a4, Slc22a2, Thbs4, and Tnni3. In established hypertension 102 genes exhibited altered expression after Bonferroni correction (P<0.05). These included Atp5o, Ech1, Fabp3, Gnb3, Ldhb, Myh6, Lpl, Pkkaca, Vegfb, Vcam1, and reduced nicotinamide-adenine dinucleotide dehydrogenases. Among the genes identified, there was an overrepresentation of gene ontology terms involved in energy production, fatty acid and lipid metabolism, oxidation, and transport. These could contribute to increases in reactive oxygen species. Our meta-analysis has revealed many new genes for which the expression is altered in hypertension, so pointing to novel potential causative, maintenance, and responsive mechanisms and pathways. PMID- 20585105 TI - Testicular cancer survivorship: research strategies and recommendations. AB - Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer. PMID- 20585108 TI - Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. AB - Ingestion of dietary (inorganic) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation. In addition, nitrite is a potent vasodilator in humans, an effect thought to underlie the blood pressure-lowering effects of dietary nitrate (in the form of beetroot juice) ingestion. Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain. Using a randomized crossover study design, we show that nitrate supplementation (KNO(3) capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO(3) (1488 mg of nitrate) versus 24 mmol of KCl [n=20]) or vegetable intake (250 mL of beetroot juice [5.5 mmol nitrate] versus 250 mL of water [n=9]) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers. In addition, post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration, whereby blood pressure is decreased in male volunteers, with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers. Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation. In addition, our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women. PMID- 20585109 TI - Tumor suppressor A20 protects against cardiac hypertrophy and fibrosis by blocking transforming growth factor-beta-activated kinase 1-dependent signaling. AB - A20 or tumor necrosis factor-induced protein 3 is a negative regulator of nuclear factor kappaB signaling. A20 has been shown previously to attenuate cardiac hypertrophy in vitro and postmyocardial infarction remodeling in vivo. In the present study, we tested the hypothesis that overexpression of A20 in the murine heart would protect against cardiac hypertrophy in vivo. The effects of constitutive human A20 expression on cardiac hypertrophy were investigated using in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding in A20 transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by echocardiography, as well as by pathological and molecular analyses of heart samples. Constitutive overexpression of human A20 in the murine heart attenuated the hypertrophic response and markedly reduced inflammation, apoptosis, and fibrosis. Cardiac function was also preserved in hearts with increased A20 levels in response to hypertrophic stimuli. Western blot experiments further showed A20 expression markedly blocked transforming growth factor-beta-activated kinase 1-dependent c-Jun N-terminal kinase/p38 signaling cascade but with no difference in either extracellular signal-regulated kinase 1/2 or AKT activation in vivo and in vitro. In cultured neonatal rat cardiac myocytes, [3H]proline incorporation and Western blot assays revealed that A20 expression suppressed transforming growth factor-beta-induced collagen synthesis and transforming growth factor-beta-activated kinase 1-dependent Smad 2/3/4 activation. In conclusion, A20 improves cardiac functions and inhibits cardiac hypertrophy, inflammation, apoptosis, and fibrosis by blocking transforming growth factor-beta-activated kinase 1-dependent signaling. PMID- 20585110 TI - Impact of cotrimoxazole on carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae in HIV-infected children in Zambia. AB - This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae as major causes of childhood mortality in HIV-infected children was investigated since these are unclear. Representative nasopharyngeal swabs were taken prior to randomization for 181 of 534 children (92 on cotrimoxazole and 89 on placebo). Bacterial identification and antibiotic susceptibility were performed by routine methods. Due to reduced mortality, prophylactic cotrimoxazole increased the median time from randomization to the last specimen from 48 to 56 months (P = 0.001). The carriage of H. influenzae was unaltered by cotrimoxazole. Carriage of S. pneumoniae increased slightly in both arms but was not statistically significant in the placebo arm. In S. pneumoniae switching between carriage and no carriage in consecutive pairs of samples was unaffected by cotrimoxazole (P = 0.18) with a suggestion that the probability of remaining carriage free was lower (P = 0.10). In H. influenzae cotrimoxazole decreased switching from carriage to no carriage (P = 0.02). Cotrimoxazole resistance levels were higher in postbaseline samples in the cotrimoxazole arm than in the placebo arm (S. pneumoniae, P < 0.0001; H. influenzae, P = 0.005). Cotrimoxazole decreased switching from cotrimoxazole resistance to cotrimoxazole sensitivity in S. pneumoniae (P = 0.002) and reduced the chance of H. influenzae remaining cotrimoxazole sensitive (P = 0.05). No associations were observed between the percentage of CD4 (CD4%), the change in CD4% from baseline, child age at date of specimen, child gender, or sampling month with carriage of either pathogen. PMID- 20585111 TI - Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. AB - BMS-790052 is the most potent hepatitis C virus (HCV) inhibitor reported to date, with 50% effective concentrations (EC(50)s) of < or = 50 pM against genotype 1 replicons. This exceptional potency translated to rapid viral load declines in a phase I clinical study. By targeting NS5A, BMS-790052 is distinct from most HCV inhibitors in clinical evaluation. As an initial step toward correlating in vitro and in vivo resistances, multiple cell lines and selective pressures were used to identify BMS-790052-resistant variants in genotype 1 replicons. Similarities and differences were observed between genotypes 1a and 1b. For genotype 1b, L31F/V, P32L, and Y93H/N were identified as primary resistance mutations. L23F, R30Q, and P58S acted as secondary resistance substitutions, enhancing the resistance of primary mutations but themselves not conferring resistance. For genotype 1a, more sites of resistance were identified, and substitutions at these sites (M28T, Q30E/H/R, L31M/V, P32L, and Y93C/H/N) conferred higher levels of resistance. For both subtypes, combining two resistance mutations markedly decreased inhibitor susceptibility. Selection studies with a 1b/1a hybrid replicon highlighted the importance of the NS5A N-terminal region in determining genotype-specific inhibitor responses. As single mutations, Q30E and Y93N in genotype 1a conferred the highest levels of resistance. For genotype 1b, BMS-790052 retained subnanomolar potency against all variants with single amino acid substitutions, suggesting that multiple mutations will likely be required for significant in vivo resistance in this genetic background. Importantly, BMS-790052-resistant variants remained fully sensitive to alpha interferon and small-molecule inhibitors of HCV protease and polymerase. PMID- 20585112 TI - Small-molecule screening using a whole-cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel antiadenoviral compound. AB - Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their antiadenoviral effect give inconsistent results. We have developed a whole cell-based assay for high throughput screening of potential antiadenoviral compounds. The assay is unique in that it is based on a replication-competent adenovirus type 11p green fluorescent protein (GFP)-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by > or = 80%, but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-{[2 (benzoylamino)benzoyl]amino}-benzoic acid, turned out to be a potent inhibitor of adenovirus replication. PMID- 20585113 TI - Different classes of antibiotics differentially influence shiga toxin production. AB - Shiga toxin (Stx) in Escherichia coli O157:H7 is encoded as a late gene product by temperate bacteriophage integrated into the chromosome. Phage late genes, including stx, are silent in the lysogenic state. However, stress signals, including some induced by antibiotics, trigger the phage to enter the lytic cycle, and phage replication and Stx production occur concurrently. In addition to the Stx produced by O157:H7, phage produced by O157:H7 can infect harmless intestinal E. coli and recruit them to produce Shiga toxin. To understand how antibiotics influence Stx production, Stx lysogens were treated with different classes of antibiotics in the presence or absence of phage-sensitive E. coli, and Stx-mediated inhibition of protein synthesis was monitored using luciferase expressing Vero cells. Growth-inhibitory levels of antibiotics suppressed Stx production. Subinhibitory levels of antibiotics that target DNA synthesis, including ciprofloxacin (CIP) and trimethoprim-sulfamethoxazole, increased Stx production, while antibiotics that target the cell wall, transcription, or translation did not. More Stx was produced when E. coli O157:H7 was incubated in the presence of phage-sensitive E. coli than when grown as a pure culture. Remarkably, very high levels of Stx were detected even when growth of O157:H7 was completely suppressed by CIP. In contrast, azithromycin significantly reduced Stx levels even when O157:H7 viability remained high. PMID- 20585114 TI - Serum and cerebrospinal fluid levels of colistin in pediatric patients. AB - Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 microg/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 microg/ml but increased in the presence of meningitis (approximately 0.5 microg/ml or 34 to 67% of serum levels). PMID- 20585115 TI - Pharmacokinetics of rifampin and clarithromycin in patients treated for Mycobacterium ulcerans infection. AB - In a randomized controlled trial in Ghana, treatment of Mycobacterium ulcerans infection with streptomycin (SM)-rifampin (RIF) for 8 weeks was compared with treatment with SM-RIF for 4 weeks followed by treatment with RIF-clarithromycin (CLA) for 4 weeks. The extent of the interaction of RIF and CLA combined on the pharmacokinetics of the two compounds is unknown in this population and was therefore studied in a subset of patients. Patients received CLA at a dose of 7.5 mg/kg of body weight once daily, rounded to the nearest 125 mg. RIF was administered at a dose of 10 mg/kg, rounded to the nearest 150 mg. SM was given at a dose of 15 mg/kg once daily as an intramuscular injection. Plasma samples were drawn at steady state and analyzed by liquid chromatography-tandem mass spectroscopy. Pharmacokinetic parameters were calculated with the MW/Pharm (version 3.60) program. Comedication with CLA resulted in a 60% statistically nonsignificant increase in the area under the plasma concentration-time curve (AUC) for RIF of 25.8 mg x h/liter (interquartile ratio [IQR], 21.7 to 31.5 mg x h/liter), whereas the AUC of RIF was 15.2 mg x h/liter (IQR, 15.0 to 17.5 mg x h/liter) in patients comedicated with SM (P = 0.09). The median AUCs of CLA and 14-hydroxyclarithromycin (14OH-CLA) were 2.9 mg x h/liter (IQR, 1.5 to 3.8 mg x h/liter) and 8.0 mg x h/liter (IQR, 6.7 to 8.6 mg x h/liter), respectively. The median concentration of CLA was above the MIC of M. ulcerans, but that of 14OH CLA was not. In further clinical studies, a dose of CLA of 7.5 mg/kg twice daily should be used (or with an extended-release formulation, 15 mg/kg should be used) to ensure higher levels of exposure to CLA and an increase in the time above the MIC compared to those achieved with the currently used dose of 7.5 mg/kg once daily. PMID- 20585116 TI - Development of daptomycin nonsusceptibility with heterogeneous vancomycin intermediate resistance and oxacillin susceptibility in methicillin-resistant Staphylococcus aureus during high-dose daptomycin treatment. PMID- 20585117 TI - Emergence of resistance among USA300 methicillin-resistant Staphylococcus aureus isolates causing invasive disease in the United States. AB - USA300 methicillin-resistant Staphylococcus aureus (MRSA) isolates are usually resistant only to oxacillin, erythromycin, and, increasingly, levofloxacin. Of these, oxacillin and levofloxacin resistances are chromosomally encoded. Plasmid mediated clindamycin, mupirocin, and/or tetracycline resistance has been observed among USA300 isolates, but these descriptions were limited to specific patient populations or isolated occurrences. We examined the antimicrobial susceptibilities of invasive MRSA isolates from a national surveillance population in order to identify USA300 isolates with unusual, possibly emerging, plasmid-mediated antimicrobial resistance. DNA from these isolates was assayed for the presence of resistance determinants and the presence of a pSK41-like conjugative plasmid. Of 823 USA300 isolates, 72 (9%) were tetracycline resistant; 69 of these were doxycycline susceptible and tetK positive, and 3 were doxycycline resistant and tetM positive. Fifty-one (6.2%) isolates were clindamycin resistant and ermC positive; 22 (2.7%) isolates were high-level mupirocin resistant (mupA positive); 5 (0.6%) isolates were trimethoprim sulfamethoxazole (TMP-SMZ) resistant, of which 4 were dfrA positive; and 7 (0.9%) isolates were gentamicin resistant and aac6'-aph2'' positive. Isolates with pSK41 like plasmids (n = 24) were positive for mupA (n = 19), dfrA (n = 6), aac6' aph2'' (n = 6), tetM (n = 2), and ermC (n = 8); 20 pSK41-positive isolates were positive for two or more resistance genes. Conjugative transfer of resistance was demonstrated between four gentamicin- and mupirocin-resistant and three gentamicin- and TMP-SMZ-resistant USA300 isolates; transconjugants harbored a single pSK41-like plasmid, which was PCR positive for aac6'-aph2'' and either mupA and/or dfrA. USA300 and USA100 isolates from the same state with identical resistance profiles contained pSK41-like plasmids with indistinguishable restriction and Southern blot profiles, suggesting horizontal plasmid transfer between USA100 and USA300 isolates. PMID- 20585118 TI - Pharmacokinetic/pharmacodynamic investigation of colistin against Pseudomonas aeruginosa using an in vitro model. AB - Colistin plays a key role in treatment of serious infections by Pseudomonas aeruginosa. The aims of this study were to (i) identify the pharmacokinetic/pharmacodynamic (PK/PD) index (i.e., the area under the unbound concentration-time curve to MIC ratio [fAUC/MIC], the unbound maximal concentration to MIC ratio [fC(max)/MIC], or the cumulative percentage of a 24-h period that unbound concentrations exceed the MIC [fT(>MIC)]) that best predicts colistin efficacy and (ii) determine the values for the predictive PK/PD index required to achieve various magnitudes of killing effect. Studies were conducted in a one-compartment in vitro PK/PD model for 24 h using P. aeruginosa ATCC 27853, PAO1, and the multidrug-resistant mucoid clinical isolate 19056 muc. Six intermittent dosing intervals, with a range of fC(max) colistin concentrations, and two continuous infusion regimens were examined. PK/PD indices varied from 0.06 to 18 for targeted fC(max)/MIC, 0.36 to 312 for fAUC/MIC, and 0 to 100% for fT(>MIC). A Hill-type model was fit to killing effect data, which were expressed as the log(10) ratio of the area under the CFU/ml curve for treated regimens versus control. With fC(max) values equal to or above the MIC, rapid killing was observed following the first dose; substantial regrowth occurred by 24 h with most regimens. The overall killing effect was best correlated with fAUC/MIC (R(2) = 0.931) compared to fC(max)/MIC (R(2) = 0.868) and fT(>MIC) (R(2) = 0.785). The magnitudes of fAUC/MIC required for 1- and 2-log(10) reductions in the area under the CFU/ml curve relative to growth control were 22.6 and 30.4, 27.1 and 35.7, and 5.04 and 6.81 for ATCC 27853, PAO1, and 19056 muc, respectively. The PK/PD targets identified will assist in designing optimal dosing strategies for colistin. PMID- 20585119 TI - Cloning and occurrence of czrC, a gene conferring cadmium and zinc resistance in methicillin-resistant Staphylococcus aureus CC398 isolates. AB - We recently reported a phenotypic association between reduced susceptibility to zinc and methicillin resistance in Staphylococcus aureus CC398 isolates from Danish swine (F. M. Aarestrup, L. M. Cavaco, and H. Hasman, Vet. Microbiol. 142:455-457, 2009). The aim of this study was to identify the genetic determinant causing zinc resistance in CC398 and examine its prevalence in isolates of animal and human origin. Based on the sequence of the staphylococcal cassette chromosome mec (SCCmec) element from methicillin-resistant S. aureus (MRSA) CC398 strain SO385, a putative metal resistance gene was identified in strain 171 and cloned in S. aureus RN4220. Furthermore, 81 MRSA and 48 methicillin-susceptible S. aureus (MSSA) strains, isolated from pigs (31 and 28) and from humans (50 and 20) in Denmark, were tested for susceptibility to zinc chloride and for the presence of a putative resistance determinant, czrC, by PCR. The cloning of czrC confirmed that the zinc chloride and cadmium acetate MICs for isogenic constructs carrying this gene were increased compared to those for S. aureus RN4220. No difference in susceptibility to sodium arsenate, copper sulfate, or silver nitrate was observed. Seventy-four percent (n = 23) of the animal isolates and 48% (n = 24) of the human MRSA isolates of CC398 were resistant to zinc chloride and positive for czrC. All 48 MSSA strains from both human and pig origins were found to be susceptible to zinc chloride and negative for czrC. Our findings showed that czrC is encoding zinc and cadmium resistance in CC398 MRSA isolates, and that it is widespread both in humans and animals. Thus, resistance to heavy metals such as zinc and cadmium may play a role in the coselection of methicillin resistance in S. aureus. PMID- 20585120 TI - Association of the extended-spectrum beta-lactamase gene blaTLA-1 with a novel ISCR element, ISCR20. AB - The bla(TLA-1) gene encoding an extended-spectrum beta-lactamase was identified in 11 enterobacterial isolates from Mexico City, Mexico. This gene was located on different plasmids and plasmid types with different sizes and incompatibility groups. It was associated with a novel insertion sequence, ISCR20, encoding a putative transposase that shared only 20% amino acid identity with the most closely related transposase of ISCR1. The ISCR20 element provided specific promoter sequences for expression of the bla(TLA-1) gene. PMID- 20585121 TI - Synergy of caspofungin with human polymorphonuclear granulocytes for killing Candida albicans. AB - The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 microg/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for the treatment of invasive fungal infections, including those refractory to conventional treatment with azole agents. PMID- 20585122 TI - Impact of multidrug-resistant Pseudomonas aeruginosa bacteremia on patient outcomes. AB - Trends of rising rates of resistance in Pseudomonas aeruginosa make selection of appropriate empirical therapy increasingly difficult, but whether multidrug resistant (MDR) P. aeruginosa is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents) P. aeruginosa bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with P. aeruginosa bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR P. aeruginosa. Patients with MDR P. aeruginosa bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively; P < 0.001) and had longer prior hospital stays (32.6 +/- 37.3 and 14.4 +/- 43.6 days, respectively; P = 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of > or = 22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (P = 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with P. aeruginosa bacteremia; efforts to curb the spread of MDR P. aeruginosa could be beneficial. PMID- 20585123 TI - Influence of empiric therapy with a beta-lactam alone or combined with an aminoglycoside on prognosis of bacteremia due to gram-negative microorganisms. AB - Evidence supporting the combination of aminoglycosides with beta-lactams for gram negative bacteremia is inconclusive. We have explored the influence on survival of empirical therapy with a beta-lactam alone versus that with a beta-lactam aminoglycoside combination by retrospectively analyzing a series of bacteremic episodes due to aerobic or facultative gram-negative microorganisms treated with single or combination therapy. The outcome variable was a 30-day mortality. Prognostic factors were selected by regression logistic analysis. A total of 4,863 episodes were assessed, of which 678 (14%) received combination therapy and 467 (10%) were fatal. Factors independently associated with mortality included age greater than 65 (odds ratio [OR], 2; 95% confidence interval [CI], 1.6 to 2.6), hospital acquisition (OR, 1.5; 95% CI, 1.2 to 1.9), a rapidly or ultimately fatal underlying disease (OR, 2.5; 95% CI, 2 to 3.2), cirrhosis (OR, 1.9; 95% CI, 1.4 to 2.6), prior corticosteroids (OR, 1.5; 95% CI, 1.1 to 2), shock on presentation (OR, 8.8; 95% CI, 7 to 11), pneumonia (OR, 2.8; 95% CI, 1.9 to 4), and inappropriate empirical therapy (OR, 1.8; 95% CI, 1.3 to 2.5). Subgroup analysis revealed that combination therapy was an independent protective factor in episodes presenting shock (OR, 0.6; 95% CI, 0.4 to 0.9) or neutropenia (OR, 0.5; 95% CI, 0.3 to 0.9). Combination therapy improved the appropriateness of empirical therapy in episodes due to extended-spectrum beta-lactamase (ESBL)- or AmpC-producing Enterobacteriaceae and Pseudomonas aeruginosa. In patients with gram-negative bacteremia, we could not find an overall association between empirical beta-lactam-aminoglycoside combination therapy and prognosis. However, a survival advantage cannot be discarded for episodes presenting shock or neutropenia, hence in these situations the use of combination therapy may still be justified. Combination therapy also should be considered for patients at risk of being infected with resistant organisms, if only to increase the appropriateness of empirical therapy. PMID- 20585124 TI - Plasmid-mediated resistance to cephalosporins in Salmonella enterica serovar Typhi. AB - This study characterized a cephalosporin-resistant Salmonella enterica serovar Typhi isolate. The organism possessed a plasmid encoding the CTX-M-15 extended spectrum-beta-lactamase. This plasmid is the determinant for the phenotype of cephalosporin resistance and is transferrable among Enterobacteriaceae. PMID- 20585125 TI - High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. AB - High-level azithromycin resistance (AZM-HR), defined as a MIC of > or = 256 mg/liter, emerged in Neisseria gonorrhoeae in the United Kingdom in 2004. To determine the mechanism of this novel phenotype, isolates from the United Kingdom that were AZM-HR (n, 19), moderately AZM resistant (MICs, 2 to 8 mg/liter) (n, 26), or sensitive (MICs, 0.12 to 0.25 mg/liter) (n, 4) were screened for methylase (erm) genes and for mutations in the mtrR promoter region, associated with efflux pump upregulation. All AZM-resistant isolates and 12 sensitive isolates were screened for mutations in domain V of each 23S rRNA allele. All AZM HR isolates contained the A2059G mutation (Escherichia coli numbering) in three (3 isolates) or four (16 isolates) 23S rRNA alleles. Most (22/26) moderately AZM resistant isolates contained the C2611T mutation in at least 3/4 alleles. The remainder contained four wild-type alleles, as did 8/12 sensitive isolates, while one allele was mutated in the remaining four sensitive isolates. Serial passage of AZM-sensitive colonies on an erythromycin-containing medium selected AZM-HR if the parent strain already contained mutation A2059G in one 23S rRNA allele. The resultant AZM-HR strains contained four mutated alleles. Eight isolates (five moderately AZM resistant and three AZM-HR) contained mutations in the mtrR promoter. No methylase genes were detected. This is the first evidence that AZM HR in gonococci may result from a single point mutation (A2059G) in the peptidyltransferase loop in domain V of the 23S rRNA gene. Mutation of a single allele is insufficient to confer AZM-HR, but AZM-HR can develop under selection pressure. The description of a novel resistance mechanism will aid in screening for the AZM-HR phenotype. PMID- 20585126 TI - In vitro activity of the new multivalent glycopeptide-cephalosporin antibiotic TD 1792 against vancomycin-nonsusceptible Staphylococcus isolates. AB - TD-1792 is a glycopeptide-cephalosporin heterodimer antibiotic with activity against a broad spectrum of gram-positive pathogens that includes methicillin susceptible and -resistant Staphylococcus aureus. The objective of the present study was to evaluate the in vitro activity of TD-1792 against a collection of clinical isolates of vancomycin-intermediate Staphylococcus spp. (VISS), heteroresistant VISS (hVISS), and vancomycin-resistant S. aureus (VRSA). The TD 1792, vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin MICs and minimum bactericidal concentrations (MBCs) were determined for 50 VISS/hVISS isolates and 3 VRSA isolates. Time-kill experiments (TKs) were then performed over 24 h with two vancomycin-intermediate S. aureus strains and two VRSA strains, using each agent at multiples of the MIC. TD-1792 and daptomycin were also evaluated in the presence and absence of 50% human serum to determine the effects of the proteins on their activities. Most of the VISS/hVISS isolates were susceptible to all agents except vancomycin. TD-1792 exhibited the lowest MIC values (MIC(90) = 0.125 microg/ml), followed by quinupristin-dalfopristin and daptomycin (MIC(90) = 1 microg/ml) and then linezolid (MIC(90) = 2 microg/ml). The presence of serum resulted in a 2- to 8-fold increase in the TD-1792 and daptomycin MIC values. In TKs, QD demonstrated bactericidal activity at multiples of the MIC that simulated therapeutic levels, whereas linezolid was only bacteriostatic. Both TD-1792 and daptomycin demonstrated rapid bactericidal activities against all isolates tested. The presence of proteins had only a minimal impact on the activity of TD-1792 in TKs. TD-1792 exhibited significant in vitro activity against multidrug-resistant Staphylococcus isolates and represents a promising candidate for the treatment of infections caused by gram positive organisms. PMID- 20585127 TI - Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum-beta-lactamase-producing Escherichia coli. AB - An increase in extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli has been observed in outpatient settings. Consequently, 100 ESBL-positive E. coli isolates from ambulatory patients with clinically confirmed urinary tract infections were collected by a single laboratory between October 2004 and January 2008. Antimicrobial susceptibility testing was carried out using the oral antibiotics fosfomycin, pivmecillinam, and nitrofurantoin and the parenteral antibiotic ertapenem. Susceptibility rates indicate that fosfomycin (97%), nitrofurantoin (94%), and pivmecillinam (85%) could be considered important oral treatment options. PMID- 20585128 TI - Easy strategy to protect antimicrobial peptides from fast degradation in serum. AB - Antimicrobial peptides are promising novel peptide leads, but their low serum stability often limits their further consideration in drug development programs. Here, we describe a generally applicable strategy to stabilize peptides against serum proteases by replacing arginine residues with alpha-amino-3-guanidino propionic acid (Agp). Peptide NH(2)-RRWRIVVIRVRR-CONH(2) was nearby totally degraded after 8 h in mouse serum, whereas the variant with Agp substituted was degraded less than 20%. The antimicrobial activity was not affected. PMID- 20585129 TI - Depolarization, bacterial membrane composition, and the antimicrobial action of ceragenins. AB - Ceragenins are cholic acid-derived antimicrobial agents that mimic the activity of endogenous antimicrobial peptides. Ceragenins target bacterial membranes, yet the consequences of these interactions have not been fully elucidated. The role of the outer membrane in allowing access of the ceragenins to the cytoplasmic membrane of gram-negative bacteria was studied using the ML-35p mutant strain of Escherichia coli that has been engineered to allow independent monitoring of small-molecule flux across the inner and outer membranes. The ceragenins CSA-8, CSA-13, and CSA-54 permeabilize the outer membrane of this bacterium, suggesting that the outer membrane does not play a major role in preventing the access of these agents to the cytoplasmic membrane. However, only the most potent of these ceragenins, CSA-13, was able to permeabilize the inner membrane. Interestingly, neither CSA-8 nor CSA-54 caused inner membrane permeabilization over a 30-min period, even at concentrations well above those required for bacterial toxicity. To further assess the role of membrane interactions, we measured membrane depolarization in gram-positive bacteria with different membrane lipid compositions, as well as in gram-negative bacteria. We found greatly increased membrane depolarization at the minimal bactericidal concentration of the ceragenins for bacterial species containing a high concentration of phosphatidylethanolamine or uncharged lipids in their cytoplasmic membranes. Although membrane lipid composition affected bactericidal efficiency, membrane depolarization was sufficient to cause lethality, providing that agents could access the cytoplasmic membrane. Consequently, we propose that in targeting bacterial cytoplasmic membranes, focus be placed on membrane depolarization as an indicator of potency. PMID- 20585130 TI - In vitro activity of tebipenem, a new oral carbapenem antibiotic, against beta lactamase-nonproducing, ampicillin-resistant Haemophilus influenzae. AB - In vitro activity of tebipenem, a new oral carbapenem antibiotic, against clinical Haemophilus influenzae isolates was compared with those of 8 reference agents. Isolates were classified into 6 resistance classes after PCR identification of beta-lactamase genes and ftsI gene mutations. For all isolates, the minimal concentration at which 90% of isolates were inhibited was lower for tebipenem than for the reference oral antibiotics, except for cefditoren. Tebipenem also showed excellent bactericidal activity against beta-lactamase nonproducing, ampicillin-resistant isolates. PMID- 20585131 TI - Clinical outcomes by methicillin-resistant Staphylococcus aureus staphylococcal cassette chromosome mec type: isolates recovered from a phase IV clinical trial of linezolid and vancomycin for complicated skin and skin structure infections. PMID- 20585132 TI - Antimicrobial susceptibility patterns for recent clinical isolates of anaerobic bacteria in South Korea. AB - We determined the antimicrobial susceptibilities of 255 clinical isolates of anaerobic bacteria collected in 2007 and 2008 at a tertiary-care hospital in South Korea. Piperacillin-tazobactam, cefoxitin, imipenem, and meropenem were highly active beta-lactam agents against most of the isolates tested. The rates of resistance of Bacteroides fragilis group organisms and anaerobic gram-positive cocci to moxifloxacin were 11 to 18% and 0 to 27%, respectively. PMID- 20585133 TI - First report of the multidrug resistance gene cfr and the phenicol resistance gene fexA in a Bacillus strain from swine feces. AB - A multidrug resistance gene, cfr, and a phenicol resistance gene, fexA, were detected in a Bacillus strain, BS-01, isolated from swine feces. The cfr gene was carried on a novel 16.5-kb plasmid, designated pBS-01. A complete Tn917 structure, which harbors the macrolide-lincosamide-streptogramin B resistance gene erm(B), was located downstream of the cfr gene. The fexA gene was discovered in the chromosomal DNA of the BS-01 strain and identified in a Tn558 variant. PMID- 20585134 TI - In vitro antimicrobial activity and mutant prevention concentration of colistin against Acinetobacter baumannii. AB - The antimicrobial activities of colistin and other antibiotics against clinical Acinetobacter baumannii and the mutant prevention concentration (MPC) of colistin against multidrug-resistant A. baumannii were studied. All 70 stains tested were sensitive to colistin. The MPC range of colistin against 30 multidrug-resistant A. baumannii stains was approximately 32 to >128 microg/ml, and the MPC at which 90% of the isolates tested were prevented (MPC(90)) exceeded 128 microg/ml, which was much higher than the plasma concentration of colistin at the current recommended dosage. So, combination therapy for colistin treatment of A. baumannii would be prudent to slow the emergence of resistance. PMID- 20585135 TI - Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis. AB - The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P < 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions. PMID- 20585142 TI - Hepatic enzyme induction: histopathology. AB - Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes. The additive growth and functional demands that initiated the response to hepatic enzyme induction cover a wide range of stimuli including pregnancy and lactation, hormonal fluctuations, dietary constituents, infections associated with acute-phase proteins, as well as responses to exposure to xenobiotics. Common xenobiotic enzyme inducers trigger pathways involving the constitutive androstane receptor (CAR), the peroxisome proliferator-activated receptor (PPAR), the aryl hydrocarbon receptor (AhR), and the pregnane-X-receptor (PXR). Liver enlargement in response to hepatic enzyme induction is typically associated with hepatocellular hypertrophy and often, transient hepatocyte hyperplasia. The hypertrophy may show a lobular distribution, with the pattern of lobular zonation and severity reflecting species, strain, and sex differences in addition to effects from specific xenobiotics. Toxicity and hepatocarcinogenicity may occur when liver responses exceed adaptive changes or induced enzymes generate toxic metabolites. These undesirable consequences are influenced by the type and dose of xenobiotic and show considerable species differences in susceptibility and severity that need to be understood for assessing the potential effects on human health from similar exposures to specific xenobiotics. PMID- 20585136 TI - Assessment of pandemic and seasonal influenza A (H1N1) virus susceptibility to neuraminidase inhibitors in three enzyme activity inhibition assays. AB - The neuraminidase inhibitors (NAIs) zanamivir and oseltamivir are currently the only antiviral drugs effective for the treatment and prophylaxis of 2009 pandemic influenza A (H1N1) virus infections. The proven potential of these viruses to acquire NAI resistance during treatment emphasizes the need to assess their NAI susceptibility. The 50% inhibitory concentrations (IC(50)s) are known to vary depending on the neuraminidase inhibition (NI) test used; however, few side-by side comparisons of different NI assays have been done. In the present study, a panel of 11 isolates representing 2009 seasonal and pandemic influenza H1N1 viruses, including oseltamivir-resistant H275Y variants, were tested in three functional NI assays: chemiluminescent (CL), fluorescent (FL), and colorimetric (CM). The sensitivities of the viruses to zanamivir, oseltamivir, and three investigational NAIs (peramivir, R-125489, and A-315675) were assessed. All isolates with the exception of H275Y variants were sensitive to all five NAIs by all three NI assays. The H275Y variants showed substantially elevated IC(50)s against oseltamivir and peramivir. The three NI assays generally yielded consistent results; thus, the choice of NI assay does not appear to affect conclusions based on drug susceptibility surveillance. Each assay, however, offers certain advantages compared to the others: the CL assay required less virus volume and the FL assay provided the greatest difference in the IC(50)s between the wild type and the variants, whereas the IC(50)s obtained from the CM assay may be the most predictive of the drug concentrations needed to inhibit enzyme activity in humans. It would be desirable to develop an NI assay which combines the advantages of all three currently available assays but which lacks their shortcomings. PMID- 20585143 TI - Early events in vascular injury in the rat induced by the phosphodiesterase IV inhibitor SCH 351591. AB - Treatment with drugs from multiple classes induces vascular injury with medial necrosis, hemorrhage, endothelial damage, and inflammation. Previous research has suggested early events might be occurring well in advance of the full lesions that appear forty-eight to seventy-two hours after dosing with SCH 351591, a PDE IV inhibitor. This study was performed to study early events in detail. Rats were dosed with 20 mg/kg of drug by gavage and sacrificed at times between fifteen and 240 minutes after dosing. Tissues were collected for histopathological analysis and gene expression studies. Serum was collected for biomarker analysis. The data from biomarker analysis showed a three-part response with an early phase that was maximal at fifteen to thirty minutes, a second phase from forty-five to 180 minutes, and the third phase that was starting to rise at four hours. The first phase included increases in lymphocytes, serum histamine, and serum nitrite. The second phase shows continued elevation of serum nitrite. The third phase was marked by an increase in serum GRO/CINC-1. At fifteen minutes, histopathology showed activation of mast cells, but not degranulation. Increases in endothelial activation and perivascular inflammatory cells were first apparent at thirty minutes and increased through 240 minutes. PMID- 20585144 TI - Effects of hepatic drug-metabolizing enzyme induction on clinical pathology parameters in animals and man. AB - Hepatic drug-metabolizing enzyme (DME) induction is an adaptive response associated with changes in preclinical species; this response can include increases in liver weight, hepatocellular hyperplasia and hypertrophy, and upregulated tissue expression of DMEs. Effects of DME induction on clinical pathology markers of hepatobiliary injury and function in animals as well as humans are not well established. This component of a multipart review of the comparative pathology of xenobiotically mediated induction of hepatic metabolizing enzymes reviews pertinent data from retrospective and prospective preclinical and clinical studies. Particular attention is given to studies with confirmation of DME induction and concurrent evaluation of liver and/or serum hepatobiliary marker enzyme activities and histopathology. These results collectively indicate that in the rat, when histologic findings are limited to hepatocellular hypertrophy, DME induction is not expected to be associated with consistent or substantive changes in serum or plasma activity of hepatobiliary marker enzymes such as alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. In the dog and the monkey, published studies also do not demonstrate a consistent relationship across DME-inducing agents and changes in these clinical pathology parameters. However, increased liver alkaline phosphatase or gamma glutamyltransferase activity in dogs treated with phenobarbital or corticosteroids suggests that direct or indirect induction of select hepatobiliary injury markers can occur both in the absence of liver injury and independently of induction of DME activity. Although correlations between tissue and serum levels of these hepatobiliary markers are limited and inconsistent, increases in serum/plasma activities that are substantial or involve changes in other markers generally reflect hepatobiliary insult rather than DME induction. Extrahepatic effects, including disruption of the hypothalamic-pituitary-thyroid axis, can also occur as a direct outcome of hepatic DME induction in humans and animals. Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans. PMID- 20585145 TI - Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat. AB - We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies. PMID- 20585146 TI - CardioVINEdb: a data warehouse approach for integration of life science data in cardiovascular diseases. AB - One of the major challenges in bioinfomatics is to integrate and manage data from different sources as well as experimental microarray data and present them in a user-friendly format. Therefore, we present CardioVINEdb, a data warehouse approach developed to interact with and explore life science data. The data warehouse architecture provides a platform independent web interface that can be used with any common web browser. A monitor component controls and updates the data from the different sources to guarantee up-todateness. In addition, the system provides a "static" and "dynamic" visualization component for interactive graphical exploration of the data. PMID- 20585147 TI - Non-invasive baroreflex sensitivity assessment using wavelet transfer function based time-frequency analysis. AB - A novel approach for the estimation of baroreflex sensitivity (BRS) is introduced based on time-frequency analysis of the transfer function (TF). The TF method (TF BRS) is a well-established non-invasive technique which assumes stationarity. This condition is difficult to meet, especially in cardiac patients. In this study, the classical TF was replaced with a wavelet transfer function (WTF) and the classical coherence was replaced with wavelet transform coherence (WTC), adding the time domain as an additional degree of freedom with dynamic error estimation. Error analysis and comparison between WTF-BRS and TF-BRS were performed using simulated signals with known transfer function and added noise. Similar comparisons were performed for ECG and blood pressure signals, in the supine position, of 19 normal subjects, 44 patients with a history of previous myocardial infarction (MI) and 45 patients with chronic heart failure. This yielded an excellent linear association (R > 0.94, p < 0.001) for time-averaged WTF-BRS, validating the new method as consistent with a known method. The additional advantage of dynamic analysis of coherence and TF estimates was illustrated in two physiological examples of supine rest and change of posture showing the evolution of BRS synchronized with its error estimations and sympathovagal balance. PMID- 20585148 TI - Gaussian mixture models for classification of neonatal seizures using EEG. AB - A real-time neonatal seizure detection system is proposed based on a Gaussian mixture model classifier. The system includes feature transformation techniques and classifier output postprocessing. The detector was evaluated on a database of 20 patients with 330 h of recordings. A detailed analysis of the choice of parameters for the detector is provided. A mean good detection rate of 79% was obtained with only 0.5 false detections per hour. A thorough review of all misclassified events was performed, from which a number of patterns causing false detections were identified. PMID- 20585149 TI - Contactless and continuous monitoring of heart rate based on photoplethysmography on a mattress. AB - This paper reports a novel contactless monitoring method to record photoplethysmogram (PPG) on a mattress for the continuous measurement of heart rate (HR). PPGs were obtained from subjects' fingers and backs with and without making a direct contact between the PPG sensor and their skin when they rested in a supine position on the mattress. Electrocardiograms (ECGs) were measured from the subjects' limbs for reference. Clear PPG waveforms were obtained from the subjects' backs. Beat-to-beat HR derived from contactless PPG measurement was comparable to those measured from contact PPG and ECG measurements. Thus we found that contactless PPG could be captured from the subjects' backs and it was sufficient to provide accurate HR measurements. This contactless monitoring of PPG has the potential to reduce obstruction in sleep and provide clinical evaluation in sleep study. PMID- 20585150 TI - The physiological impact of the nonlinearity of arterial elasticity in the ambulatory arterial stiffness index. AB - The ambulatory arterial stiffness index (AASI) is claimed to be a new estimator for arterial rigidity. It was recently defined as one minus the slope of the linear regression of systolic to diastolic ambulatory pressure during 24 h. Although several reports testify its clinical relevance, the explanation of how this new index is conceptually associated with arterial stiffness remains controversial. In this work we hypothesize that nonlinear arterial elasticity is behind AASI physiological principles. To that end, random number generators were used to emulate arterial cross-sectional area (CSA) during 24 h. Pressure values were calculated using linear and nonlinear elasticity models for rigid and compliant arteries. The AASI was calculated from simulated pressures and also analytically predicted for each model. Additionally, invasive aortic pressure and CSA were continuously measured in a conscious sheep during 24 h to test the nonlinear model. We found that analytical solutions agreed with simulation outcomes; for the nonlinear model, the AASI was higher in rigid arteries with respect to compliant arteries (0.51 versus 0.38) and the linear model systematically predicted AASI = 0. For in vivo pressure measurements, AASI was 0.31. Using the measured pulsatile CSA and an estimation of the elastic constant for the nonlinear model, the AASI was accurately predicted with errors below 5%. We conclude that the AASI is higher in stiffer arteries due to the nonlinear behavior of the arterial wall. With a nonlinear arterial function, the slope of the linear regression of diastolic to systolic pressures during 24 h depends on the product of an elastic constant by the pulsatile CSA. As the elastic constant dominates the product, the reported associations between the AASI and arterial stiffness indices now have a consistent explanation. PMID- 20585151 TI - Folate targeted polymeric 'green' nanotherapy for cancer. AB - The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)-'NanoGSE'-was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size approximately 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC(50) values were lowered by a factor of approximately 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach. PMID- 20585152 TI - Thermal stability of high-k Si-rich HfO(2) layers grown by RF magnetron sputtering. AB - The microstructure and optical properties of HfSiO films fabricated by RF magnetron sputtering were studied by means of x-ray diffraction, transmission electron microscopy, spectroscopic ellipsometry and attenuated total reflection infrared spectroscopy versus annealing treatment. It was shown that silicon incorporation in the HfO(2) matrix plays an important role in the structure stability of the layers. Thus, the increase of the annealing temperature up to 1000 degrees C did not lead to the crystallization of the films. The evolution of the chemical composition as well as a decrease of the density of the films was attributed to the phase separation of HfSiO on HfO(2) and SiO(2) phases in the film. An annealing at 1000-1100 degrees C results in the formation of the multilayer Si-rich/Hf-rich structure and was explained by a surface-directed spinodal decomposition. The formation of the stable tetragonal structure of HfO(2) phase was shown upon annealing treatment at 1100 degrees C. PMID- 20585153 TI - Nanotwinned gold nanowires obtained by chemical synthesis. AB - We demonstrate a facile method for synthesizing and isolating Au nanowires with a high density of twin boundary defects normal to the growth axis. In this process, oleylamine conveniently plays the role of the solvent, the reducing agent and the ligand. The geometry of the twin boundaries in the nanowires is in sharp contrast with the pentagonal twinning commonly observed in metal nanowires, and is of particular interest for its ultrahigh tensile strength. The nanostructure geometry and twin-twin average spacing were characterized using high-resolution electron microscopy, and the tensile strength of the nanowires was estimated in solution using a Ti ultrasonication probe. We present a model for explaining the role of the bulky ligand oleylamine in the formation of the twin boundaries that could be extended to include elastic terms in the ligand shell. Our work demonstrates that the use of bulky, asymmetric ligands can induce extensive formation of twin boundary defects that in turn control the mechanical properties at the nanoscale. PMID- 20585154 TI - Sub-10 nm crystalline silicon nanostructures by electron beam induced deposition lithography. AB - A novel top-down approach for the controllable fabrication of semiconductor nanostructures exhibiting quantum effects is described. By decomposing metal-rich precursor gas molecules with an electron beam, a sub-10 nm metal pattern can be formed and subsequently transferred to a semiconductor substrate. In such a way monocrystalline silicon nanodots and nanowires are produced as revealed by transmission electron microscopy. It is also shown how through controlled thermal or chemical oxidation the nanostructure surface can be passivated. By providing direct access to the sub-10 nm size range this method possesses promising potential for application in the quantum dot and nanoelectronics fields. PMID- 20585155 TI - Coaxial ZnSe/Si nanocables with controlled p-type shell doping. AB - Coaxial ZnSe/Si nanocables were successfully produced by a simple two-step growth method. ZnSe nanowire cores were first synthesized by thermal evaporation and then followed by the chemical vapor deposition (CVD) growth of Si shells. The former have a cubic single-crystal structure with a longitudinal direction of [Formula: see text], while the latter are polycrystalline and composed of a large number of Si crystal grains with dominantly (111) surfaces. Controlled p-type doping to the Si shells was implemented by B diffusion after the shell growth. Electrical measurements on the Si shells demonstrated that the shell conductivity could be tuned in a wide range of eight orders of magnitude by adjusting the B concentration, and a hole mobility of 11.7 cm(2) V( - 1) s( - 1) and a hole concentration of 2 x 10(15) cm( - 3) were revealed for the modestly doped Si shells. The ZnSe/Si core/shell nanocables have great potential in nano optoelectronic applications. PMID- 20585156 TI - Molecular heterojunction morphology on rough substrate surfaces: component separation by Fourier subtraction. AB - The study of molecular heterojunction morphology is often complicated by the presence of a topographically complex substrate. On such substrates, it is difficult to definitively assign a topographic feature to a specific component. We propose a technique, based on the separation of features in reciprocal space (Fourier subtraction), to deconvolute a heterojunction surface into two real space images. The technique has been successfully applied to three classes of systems: (1) where the overlayer features are smaller than those of the substrate, such as with small molecule growth on polymer substrates (DIP/PEDOT:PSS); (2) where the overlayer features are larger than the substrate, such as with a polymer film in contact with a corrugated metal surface (P3HT/Al), and (3) where both the overlayer and substrate features are of the same size. The Fourier subtraction method extends the study of morphology to heterojunctions with realistic substrates, where the complex topography may previously have prevented a basic description of the specific features of each component in a heterojunction film. PMID- 20585157 TI - Non-specific cellular uptake of surface-functionalized quantum dots. AB - We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically significant moieties, e.g. carboxyl, amino, and streptavidin, were used, in combination with surface derivatization with polyethylene glycol (PEG) for a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specific internalization is undesirable and when it is intended for material to be internalized as efficiently as possible. PMID- 20585158 TI - Ferrocene-coated CdSe/ZnS quantum dots as electroactive nanoparticles hybrids. AB - Electrochemical properties of core-shell CdSe/ZnS quantum dots (QDs) in a non aqueous solution are presented. Cathodic reduction and anodic oxidation processes involving the QD HOMO and LUMO levels as well as defect states were identified by cyclic voltammetry. The electrochemical bandgap was estimated from the anodic and cathodic redox peaks and found to match well with the optical bandgap estimated from the absorption spectrum. The trioctylphosphine oxide ligands on the surface of the QDs were exchanged to electroactive ferrocenyl thiols and the resulting material was characterized by NMR and optical spectroscopy. Cyclic voltammetry showed that the redox potentials of the QDs are modified due to the presence of ferrocene on the surface of the QD. The QD oxidation peak decreased and the reduction peak shifted to more negative potentials. The concurrent shift of the ferrocene redox peaks indicates that the system displays features of a 'molecular hybrid', where both the QD and the ligand influence each other. PMID- 20585159 TI - Design and evaluation of quantum dot sensors for making superficial x-ray energy radiation measurements. AB - The extraordinary physical properties of quantum dot (QD) materials such as high radiation sensitivity and good radiation resistivity indicate their potential for use in the fabrication of radiation sensors. This paper reports the design and fabrication of two kinds of radiation sensors based on ZnO and CdTe QDs. Both sensors are characterized using a Gulmay Medical D3000 DXR unit for superficial x ray irradiation with source photon energies that range from 36.9 to 64.9 keV. The QD radiation sensors exhibit excellent linearity with respect to different photon energy doses, radiation source to device surface distances, and field sizes. The effects of the electrode separation and the area density of the QD layer are also investigated. All sensors characterized show an outstanding repeatability under photon irradiation, with a signal variation less than 1%. PMID- 20585160 TI - Focused electron beam induced etching of silicon using chlorine. AB - A new beam-assisted process for removing silicon from a surface in the nanometer scale in a conventional scanning electron microscope is presented. This approach is based on focused electron beam induced etching with pure chlorine gas being used as the precursor. In contrast to the established etching process using a focused ion beam (with or without the addition of a precursor), no amorphization and gallium implanting of the substrate takes place. The observed low etch rates facilitate removal with sub-nanometer precision. No spontaneous etching of silicon as in the case of xenon difluoride was observed. Etch rates of up to 4 nm min( - 1) could be achieved as well as a minimum feature size of below 80 nm. The effect of etching parameters like electron beam energy, electron beam accelerating voltage or pixel spacing were systematically examined. Finally, the underlying etching mechanism in terms of secondary electron interactions and precursor replenishment is discussed. PMID- 20585161 TI - The intriguing thermal conductivity of ice nanotubes. AB - We have investigated the thermal conductivity of various ice nanotubes (Ice-NTs) using the nonequilibrium molecular dynamics method. The results indicate that Ice NTs have an unusually high thermal conductivity compared to that of the bulk ices. The thermal conductivity is sensitive to temperature, tube length and diameter, while being insensitive to polarization. We have also studied the confinement effect from single-walled carbon nanotubes (SWCNs). A very remarkable increase in the thermal conductivity is further observed after the Ice-NTs are confined in SWCNs. PMID- 20585162 TI - Continuous depth-sensing nano-mechanical characterization of living, fixed and dehydrated cells attached on a glass substrate. AB - Continuous depth-sensing nano-indentation on living, fixed and dehydrated fibroblast cells was performed using a dynamic contact module and vertically measured from a pre-contact state to the glass substrate. The nano-indentation tip-on-cell approaches took advantage of finding a contact surface, followed by obtaining a continuous nano-mechanical profile along the nano-indentation depths. In the experiment, serial indentations from the leading edge, i.e., the lamellipodium to nucleus regions of living, fixed and dehydrated fibroblast cells were examined. Nano-indentations on a living cell anchored upon glass substrate were competent in finding the tip-on-cell contact surfaces and cell heights. For the result on the fixed and the dehydrated cells, cellular nano-mechanical properties were clearly characterized by continuous harmonic contact stiffness (HCS) measurements. The relations of HCS versus measured displacement, varied from the initial tip-on-cell contact to the glass substrate, were presumably divided into three stages, respectively induced by cellular intrinsic behavior, the substrate-dominant property, and the substrate property. This manifestation is beneficial to elucidate how the underlying substrate influences the interpretation of the nano-mechanical property of thin soft matter on a hard substrate. These findings, based upon continuous depth-sensing nano-indentations, are presumably valuable as a reference to related work, e.g., accomplished by atomic force microscopy. PMID- 20585164 TI - Nanoporous thin films with controllable nanopores processed from vertically aligned nanocomposites. AB - Porous thin films with ordered nanopores have been processed by thermal treatment on vertically aligned nanocomposites (VAN), e.g., (BiFeO(3))(0.5):(Sm(2)O(3))(0.5) VAN thin films. Uniformly distributed nanopores with an average diameter of 60 nm and 150 nm were formed at the bottom and top of the nanoporous films, respectively. Controllable porosity can be achieved by adjusting the microstructure of VAN (BiFeO(3)):(Sm(2)O(3)) thin films and the annealing parameters. In situ heating experiments within a transmission electron microscope (TEM) column at temperatures from 25 to 850 degrees C, provides significant insights into the phase transformation, evaporation and structure reconstruction during the annealing. The in situ experiments also demonstrate the possibility of processing vertically aligned nanopores (VANP) with one phase stable in a columnar structure. These nanoporous thin films with controllable pore size and density could be promising candidates for thin film membranes and catalysis for fuel cell and gas sensor applications. PMID- 20585163 TI - Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles. AB - Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml( - 1) TQ for 50% 2,2-diphenyl-1 picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 +/- 0.002 mg ml( - 1)) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 +/- 5.6% after 96 h. PMID- 20585165 TI - Increased stability of mercapto alkane functionalized Au nanoparticles towards DNA sensing. AB - The use of gold nanoparticles (GNPs) in bioassays is often hampered by their colloidal stability. In this study, gold nanoparticles coated with different mercapto alkanes were investigated towards their stability. Hereto, the effects of the alkane chain length (5-11 methylene groups), the type of functional end group (-OH or -COOH) and the amount of incorporated poly-ethylene oxide units (none, 3 or 6) on the GNP stabilization was evaluated. Based on these results, an optimal mercapto alkane (HS(CH(2))(11)PEO(6)COOH) was selected to increase the colloidal stability up to 2 M NaCl. Furthermore, it was proved that this mercapto alkane is ideally suited to enhance the stability of DNA functionalized GNPs in high electrolytic hybridization buffers. The effectiveness of these DNA functionalized GNPs was demonstrated in a sandwich assay using a surface plasmon resonance biosensor. The superior stability of these nanoparticles during hybridization may lead to enhanced biosensor technologies. PMID- 20585166 TI - Controlled fabrication of Si nanocrystals embedded in thin SiON layers by PPECVD followed by oxidizing annealing. AB - The controlled fabrication of Si nanocrystals embedded in thin silicon oxynitride films (<15 nm) on top of a silicon substrate has been realized by PPECVD with N(2)O-SiH(4) precursors. The effect of inert and oxidizing annealing processes on the Si nanocrystal spatial and size distributions is studied by coupling ellipsometry measurements and cross-sectional transmission electron microscopy observations. This study gives an interesting insight into the physics underlying the Si nanocrystal nucleation, growth and oxidation mechanisms. In particular, it evidences the presence in the as-deposited films of a high density of small amorphous Si particles that crystallize after high temperature thermal annealing. Annealing under oxidizing conditions is shown to be a powerful way to create tunnel oxides of good quality and controlled thickness needed to design future memory devices. PMID- 20585167 TI - Enhancing the conductivity of transparent graphene films via doping. AB - We report chemical doping (p-type) to reduce the sheet resistance of graphene films for the application of high-performance transparent conducting films. The graphene film synthesized by chemical vapor deposition was transferred to silicon oxide and quartz substrates using poly(methyl methacrylate). AuCl(3) in nitromethane was used to dope the graphene films and the sheet resistance was reduced by up to 77% depending on the doping concentration. The p-type doping behavior was confirmed by characterizing the Raman G-band of the doped graphene film. Atomic force microscope and scanning electron microscope images reveal the deposition of Au particles on the film. The sizes of the Au particles are 10-100 nm. The effect of doping was also investigated by transferring the graphene films onto quartz and poly(ethylene terephthalate) substrates. The sheet resistance reached 150 Omega/sq at 87% transmittance, which is comparable to those of indium tin oxide conducting film. The doping effect was manifested only with 1-2 layer graphene but not with multi-layer graphene. This approach advances the numerous applications of graphene films as transparent conducting electrodes. PMID- 20585169 TI - Selective epitaxy of semiconductor nanopyramids for nanophotonics. AB - We present a detailed study of the parameters which affect the geometrical perfection of nanopyramids used for the site-selected nucleation of quantum dots. Through an understanding of crystal facet formation, we demonstrate that undesirable high index planes can be suppressed using carefully optimized lithography together with properly orientated source fluxes in the growth reactor. High quality InP nanopyramids are reported with individual InAs/InP quantum dots positioned with high precision. This represents an important milestone for the fabrication of complex quantum dot based nanophotonic devices. PMID- 20585168 TI - Additive controlled synthesis of gold nanorods (GNRs) for two-photon luminescence imaging of cancer cells. AB - Gold nanorods (GNRs) with a longitudinal surface plasmon resonance peak that is tunable from 600 to 1100 nm have been fabricated in a cetyl trimethylammoniumbromide (CTAB) micellar medium using hydrochloric acid and silver nitrate as additives to control their shape and size. By manipulating the concentrations of silver nitrate and hydrochloric acid, the aspect ratio of the GNRs was reliably and reproducibly tuned from 2.5 to 8. The GNRs were first coated with polyelectrolyte multilayers and then bioconjugated to transferrin (Tf) to target pancreatic cancer cells. Two-photon imaging excited from the bioconjugated GNRs demonstrated receptor-mediated uptake of the bioconjugates into Panc-1 cells, overexpressing the transferrin receptor (TfR). The bioconjugated GNR formulation exhibited very low toxicity, suggesting that it is biocompatible and potentially suitable for targeted two-photon bioimaging. PMID- 20585170 TI - Nanoparticle fractionation using an aligned carbon nanotube array. AB - A technique utilizing the capillary assisted sieving capability of carbon nanotubes (CNTs) to achieve fractionation of nanoparticles of small size distribution is presented. By dipping aligned CNT arrays into a solution comprising different sized quantum dots (QDs), size-selective gradient decoration of QDs onto CNTs is achieved. The fractionating capability of CNTs is also demonstrated for poly-dispersed manganese doped zinc sulfide nanoparticles and QDs of varying sizes and chemical compositions, which we attribute to the size selective sieving effect of CNTs. By controlling the terminating point for the flow of QDs across the CNT array, a QD size specific CNT/QD hybrid structure is achieved. PMID- 20585171 TI - The growth of silica and silica-clad nanowires using a solid-state reaction mechanism on Ti, Ni and SiO(2) layers. AB - A large area compatible and solid-state process for growing silica nanowires is reported using nickel, titanium and silicon dioxide layers on silicon. The silica nanowires also contain silicon, as indicated by Raman spectroscopy. The phonon confinement model is employed to measure the diameter of the Si rich tail for our samples. The measured Raman peak shift and full width at half-maximum variation with the nanowire diameter qualitatively match with data available in the literature. We have investigated the effect of the seedbed structure on the nanowires, and the effect of using different gas conditions in the growth stages. From this, we have obtained the growth mechanism, and deduced the role of each individual substrate seedbed layer in the growth of the nanowires. We report a combined growth mechanism, where the growth is initiated by a solid-liquid-solid process, which is then followed by a vapour-liquid-solid process. We also report on the formation of two distinct structures of nanowires (type I and type II). The growth of these can be controlled by the use of titanium in the seedbed. We also observe that the diameter of the nanowires exhibits an inverse relation with the catalyst thickness. PMID- 20585172 TI - Characterization of interface abruptness and material properties in catalytically grown III-V nanowires: exploiting plasmon chemical shift. AB - We have studied the assessment of chemical composition changes in III-V heterostructured semiconductor nanowires (NWs) with nanometric spatial resolution using transmission electron microscopy methods. These materials represent a challenge for conventional spectroscopy techniques due to their high sensitivity to electron beam irradiation. Radiation damage strongly limits the exposure time to a few (5-10) s, which reduces the sensitivity of the traditionally used x-ray spectroscopy. The rather low counting statistics results in significant errors bars for EDS chemical quantification (5-10%) and interface width determination (few nanometers). Plasmon chemical shift is ideal in this situation, as its measurement requires very short exposure times (approximately 100 ms) and the plasmon peak energy can be measured with high precision (approximately 20 meV in this work). This high sensitivity allows the detection of subtle changes (1-2%) in composition or even the detection of a small plasmon energy (33 +/- 7) meV change along usually assumed pure and homogeneous InAs segments. We have applied this approach to measure interface widths in heterostructure InAs/InP NWs grown using metal catalysts and also to determine the timescale (approximately 10 s) in which beam irradiation induces material damage in these wires. In particular, we have detected small As concentrations (4.4 +/- 0.5)% in the final InP segment close to the Au catalyst, which leads to the conclusion that As diffuses through the metal nanoparticle during growth. PMID- 20585173 TI - The use of ion-milling to control clustering of nanostructured, columnar thin films. AB - We present the use of ion-milling to reduce the capillary-induced clustering of vertical post nanostructures grown by glancing angle deposition. Nanostructures of several heights were grown and ion-milled for various times to investigate effects on post clustering. No clustering was observed given sufficient ion-mill exposure time, with the characteristic time being lower for shorter posts. The results demonstrate that these strengthened nanostructures are suitable for use in liquid environments. PMID- 20585174 TI - Vertically oriented epitaxial germanium nanowires on silicon substrates using thin germanium buffer layers. AB - We demonstrate a method to realize vertically oriented Ge nanowires on Si(111) substrates. Ge nanowires were grown by chemical vapor deposition using Au nanoparticles to seed nanowire growth via a vapor-liquid-solid growth mechanism. Rapid oxidation of Si during Au nanoparticle application inhibits the growth of vertically oriented Ge nanowires directly on Si. The present method employs thin Ge buffer layers grown at low temperature less than 600 degrees C to circumvent the oxidation problem. By using a thin Ge buffer layer with root-mean-square roughness of approximately 2 nm, the yield of vertically oriented Ge nanowires is as high as 96.3%. This yield is comparable to that of homoepitaxial Ge nanowires. Furthermore, branched Ge nanowires could be successfully grown on these vertically oriented Ge nanowires by a secondary seeding technique. Since the buffer layers are grown under moderate conditions without any high temperature processing steps, this method has a wide process window highly suitable for Si based microelectronics. PMID- 20585175 TI - Synthesis of Sn doped CuO nanotubes from core-shell Cu/SnO(2) nanowires by the Kirkendall effect. AB - Sn doped CuO nanotubes were synthesized by thermal oxidization of Cu/SnO(2) core shell nanowires in air through the Kirkendall effect. The Cu/SnO(2) core-shell nanowires were sequentially electrodeposited by forming a SnO(2) shell followed by electrodeposition of the Cu core. After thermal treatment in air, the core shell Cu/SnO(2) (13 +/- 2 nm thick shell on 128 +/- 15 nm in diameter core) nanowires were oxidized to form Sn doped CuO nanotubes with an average wall thickness and outer diameter of 54 nm and 176 nm, respectively. Room temperature I-V characterization indicated that the electrical resistivity of the nanostructures was 870 +/- 85 Omega cm. The methodology that was demonstrated is very general and could be used to synthesize coaxial SnO(2) shells with a variety of electrodeposited cores. In addition, doped metal oxide nanotubes can be readily synthesized by thermal oxidization of core-shell nanowires in air where the dopant content can be tuned by controlling the shell thickness through adjusting the deposition time. PMID- 20585176 TI - Plasma nanocoated carbon nanotubes for heat transfer nanofluids. AB - Multi-wall carbon nanotubes (CNTs) were plasma-treated using glow discharges of argon, oxygen and methane/oxygen mixtures and then dispersed into a base fluid of water. It was found that proper plasma treatments of CNTs using nanoscale plasma coatings significantly improve the dispersion and stabilize the suspension of CNTs in the base fluid. With 0.01 vol% addition of plasma-treated CNTs, a 25% initial increase in thermal conductivity was achieved and a stabilized 20% increase was observed with the resulting nanofluids after 5 days' settling. It should particularly be pointed out that such a large increase in thermal conductivity was achieved when plasma-treated CNTs were stably dispersed in water without adding any dispersing agents or surfactants. Surface modification of the CNTs was confirmed by Raman spectroscopy and ultra-thin (approximately 2 nm) plasma nanocoatings were noted on the treated CNT surfaces by transmission electron microscopy (TEM). PMID- 20585177 TI - [CKD-MBD (chronic kidney disease-mineral and bone disorder). CKD-MBD: chronic kidney disease-mineral and bone disorder]. AB - Disturbances in bone and mineral metabolism in patients with chronic kidney disease (CKD) affect not only the bone diseases but also other organ disorders in the whole body and deteriorate the survival of these patients. The term CKD Mineral and Bone Disorder (CKD-MBD) has been established describing a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD. Vascular calcification and secondary hyperparathyroidism are major diseases in CKD-MBD. PMID- 20585178 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). CKD-MBD in CKD patients not yet on dialysis; Status Quo]. AB - As late interventions for CKD-MBD from stage 5D have been revealed insufficient, treatment from earlier CKD stages, or predialysis stages, is now being focused. It is very important to investigate the mechanism underlying predialysis CKD-MBD before we proceed to the treatment. In this paper, possible treatment options for CKD-MBD in predialysis patients are briefly presented, according to the knowledge and hypothesized mechanism we have so far. More evidences need to be cumulated for the future guidelines for CKD-MBD in CKD patients not yet on dialysis. PMID- 20585179 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Paradigm shift in CKD-MBD guideline]. AB - It has been recognized that deranged mineral metabolism in CKD results not only in bone diseases but also in a higher risk of mortality, Accordingly, instead of the classic term "Renal Osteodystrophy (ROD) , "a new term, "CKD-Mineral and Bone Disorders (CKD-MBD), "has recently been proposed as a systemic disorder, with cardiovascular disease, fractures, and mortality as major outcomes. The Japanese Society for Dialysis Therapy (JSDT) clinical practice guideline for the management of secondary hyperparathyroidism in chronic dialysis patients was originally published in 2006. Then, new therapeutic modalities including cinacalcet and lanthanum carbonate have recently been introduced into the Japanese market, after JSDT guideline was published. Now, the revised version of the guideline has been prepared. PMID- 20585180 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). KDIGO CKD-MBD Clinical Practice Guideline]. AB - KDIGO published the first clinical practice guideline on CKD-MBD in 2009. The work group for this guideline consisted of well-known international experts including Masafumi Fukagawa from Japan and truly global in nature. This guideline is based on strict systemic evidence review and explore a new clinical dimension that aims to improve clinical outcome of individual patient but not only improve values of surrogate markers. This guideline is truly the result of international coordinate effort especially by 5 guideline organizations. PMID- 20585181 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Role of FGF23-Klotho axis in CKD-MBD]. AB - FGF23 is a novel bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 binds to FGF receptor1 (FGFR1) -Klotho complex in the kidney and thereby induces phosphaturia and suppresses 1,25-dihydroxyvitamin D synthesis. In patients with chronic kidney disease (CKD) , circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to secondary hyperparathyroidism. In patients undergoing dialysis, FGF23 levels are markedly elevated in response to hyperphosphatemia and active vitamin D therapy, which in turn cause hypophosphatemia and reduced 1,25-dihydroxyvitamin D after kidney transplantation. FGF23 also acts directly on the parathyroid to decrease parathyroid hormone synthesis and secretion; however, in end-stage CKD patients, markedly elevated FGF23 fails to suppress the secretion of parathyroid hormone. Recent data suggest that this parathyroid resistance to FGF23 may be caused by decreased expression of FGFR1-Klotho complex in hyperplastic parathyroid glands. Further elucidation of FGF23-Klotho axis will help us to improve the understanding of the pathogenesis of CKD-mineral and bone disorder. PMID- 20585182 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Bone metabolism in CKD-MBD]. AB - "Abnormality in bone metabolism" is one of the three components that construct CKD-MBD besides "abnormality in laboratory examination" and "abnormality in soft tissue calcification". However, not all the bone metabolic disorders found in CKD patients are regarded as symptoms of CKD-MBD. Generally, bone metabolic abnormality in CKD-MBD is recognized as that caused by abnormality in systemic mineral metabolism associated with CKD. Bone metabolism in CKD-MBD displays wide spectrum. Conventionally, bone metabolism in CKD patients was classified into 5 categories according to two assessment axis, "bone cell activity" and "bone mineralization". Recently, a new system called "Turnover Mineralization-Volumec (TMV) classification" was advocated that applied cancellous bone volume as another major assessment axis. However, both the new and the old are totally dependent on histological findings, and therefore they are practically no use at bedside. It is highly desirable to establish new classification based on non invasive study results and clinical outcomes. PMID- 20585183 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Effect of vitamin D on kidney and cardiovascular system]. AB - Recently, many investigators have reported that treatment with vitamin D improves outcomes of patients with chronic kidney disease. Though the detailed mechanisms have remained unclear, it has been speculated that such a treatment may prevent progression of chronic kidney disease and cardiovascular disease. It has been reported that Vitamin D may attenuate renal injury and ameliorate renal function and proteinuria. In addition, several studies have shown that vitamin D may prevent progression of atherosclerosis, vascular calcification and left ventricular hypertrophy. The emerging experimental and clinical evidence has suggested that vitamin D may protect kidney and cardiovascular system. PMID- 20585184 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Gene therapy for secondary hyperparathyroidism]. AB - Secondary hyperparathyroidism (SHPT) is one of the most important complications of chronic kidney disease. Although 1,25-D pulse therapy is effective for SHPT, hyperplastic parathyroid (PT) cells gradually develop resistance to 1,25-D. Vitamin D(3) receptor (VDR) levels are decreased in the PT glands of dialysis patients and animal models of renal failure. To develop a new approach to such rebellious tissue, recent research has shown that the functionality protein can be adjusted with the gene transfer to the parathyroid. The experiment using adenovirus clarifies that the gene transfer of VDR and calcium sensing receptor is enabled, and such a gene expression is induced. In the recent research, we examined both in vitro and in vivo the potential use of RNAi to suppress PTH production in PT cells of SHPT patients. These results provide the findings to understand the mechanism and new treatment to SHPT. PMID- 20585185 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Atheroma and vascular calcification in hemodialysis patients]. AB - Cardiovascular complications due to accelerated atherosclerosis and arterial stiffening are the principal cause of morbidity and mortality in patients with dialysis. Both are frequently associated with vascular calcification. Uremia specific factors are considered to play an important role in promoting these aortic wall changes, and may be more important than classical atherogenic risk factors. Disorders of calcium and phosphorus metabolism and secondary hyperparathyroidism have been recognized as independent risk factors of bone disease, and also soft tissue calcification, including arterial calcification and atheroma. The best strategy to treat, or even prevent, this complication would consist of control of serum phosphate concentration. PMID- 20585186 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Bone quality in chronic kidney disease : enzymatic and non-enzymatic glycation or oxidation induced cross-links in bone]. AB - Collagen cross-link formation in bone plays an important role in bone strength and the proper biological function of bone (Saito M, Osteoporos Int, [REVIEW] 2010). Plasma homocysteine (Hcys) level and oxidative stress are increased in patient with chronic kidney disease (CKD) at stage 3. Such moderately increased plasma content of Hcys and oxidative stress are well known to be an independent fracture risk. In a case-controlled study, a significant reduction in the actual amount of enzymatic cross-links and a marked increased in advanced glycation end products cross-link, pentosidine, in bone from patients with post-menopausal osteoporotic hip fracture showing hyperhomocysteinemia (Saito M, Calcif Tissue Int 2006). Additionally, hyperhomocysteinemia induced animal model also showed the same collagen cross-links abnormalities as patients with hyperhomocysteinemia (Saito M, Osteoporos Int, 2010). In this review, we summarized the recent literature. PMID- 20585187 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). The impact of CKD MBD on mortality]. AB - The final goal of CKD-MBD (chronic kidney disease, mineral and bone disorder) is to reduce the risk of death in uremic patients. To achieve this objective, it is of importance to manage laboratory abnormalities, bone abnormalities, and vascular calcification appropriately. Many observation studies suggested that the good control of serum phosphate, calcium, and PTH concentration would lead to the lower risk of death. Fracture and vascular calcification would increase the risk for mortality. In addition, some randomized clinical trials have shown that the use of CKD-MBD related drugs, e.g. vitamin D, phosphate binder, might lead to reductions in the risk of death. PMID- 20585188 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Role of cinacalcet in the treatment of CKD-MBD]. AB - Cinacalcet, a calcium receptor modulator, reduces serum phosphate levels as well as parathyroid hormone (PTH) and serum calcium levels, and improve the control of mineral metabolic disorder, which is a major problem by the active vitamin D sterols in the treatment of secondary hyperparathyroidism. In addition, cinacalcet could improve achievement of the biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD) recommended by K/DOQI and Japanese society for dialysis and therapy (JSDT) guidelines. Some clinical studies clarified the improvement of reduction in PTH levels and achievement targets for serum calcium and phosphate levels by the combined therapy with cinacalcet and vitamin D sterols, such as OPTIMA or ACHIEVE study. However, the effect of therapy may be different which medicine would be used mainly, further examination about the way to combine these two medicines is required. From the results of some experimental and clinical examinations, cinacalcet may have some efficiency on the prevention or regression of the parathyroid hyperplasia, onset of cardiovascular disease and ectopic calcification, prevention of bone fracture, and improvement of bone metabolism or mortality. Various efficient role of cinacalcet in the treatment of CKD-MBD would be elucidated if results of the clinical studies ongoing now, such as EVOLVE and ADVANCE or MBD-5D planning in Japan, will be published in the near future. PMID- 20585189 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Lanthanum carbonate and new phosphate binders in patients with chronic kidney disease]. AB - Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs. PMID- 20585190 TI - [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Parathyroid interventions: final one piece in the management of uremic SHPT patients]. AB - The term "renal osteodystrophy" has recently been replaced with "CKD-mineral and bone disorder (CKD-MBD)", which includes vascular calcification as well as bone abnormalities. Following this paradigm shift, the Japanese Society for Dialysis Therapy released guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients, which prioritized improvement in survival, but not in bone abnormalities. According to these guidelines, parathyroid intervention, such as parathyroidectomy and percutaneous ethanol injection therapy, should be indicated if mineral disorders cannot be managed by pharmacological means. Recently, several novel therapeutic tools, including sevelamer hydrochloride, calcitriol analogs, and cinacalcet hydrochloride have been introduced in the clinical setting in Japan. The other side 2009 KDIGO guideline suggest that, if the intact PTH levels fall below two times the upper limit of normal for the assay, calcitriol, vitamin D analogs, and/or calcimimetics be reduced or stopped. And in patients with CKD stages 3-5D with severe hyperparathyroidism (HPT) who fail to respond to medical/pharmacological therapy, this guideline suggest parathyroidectomy. Harmonizing these therapeutic modalities and parathyroid interventions, we should expect more effective management of CKD-MBD, leading to the improvement of morbidity and mortality in this patient population. In this part, we consider indication of parathyroid interventions surround the present condition. PMID- 20585191 TI - Pre-heparin serum lipoprotein lipase concentrations in obese men of contrasting physical activity status: a preliminary study. PMID- 20585192 TI - Comparative study of cerebellar degeneration in canine neuroaxonal dystrophy, cerebellar cortical abiotrophy, and neuronal ceroid-lipofuscinosis. AB - The cerebellar lesions of three dogs with canine neuroaxonal dystrophy (NAD), one dog with cerebellar cortical abiotrophy (CCA), and 4 dogs with neuronal ceroid lipofuscinosis (NCL) were examined to understand their pathogeneses. Purkinje cell loss was most severe in the vermis of a dog with CCA, and granule cell loss was most prominent in the cerebellar hemisphere of dogs with NCL. Immunohistochemically, CD3-and HLA-DR-positive cells were most frequent in the dogs with NCL, and moderate in dogs with NAD, but not in a dog with CCA. The number of cleaved caspase 3-positive cells was prominent in a dog with CCA, but no significant in the dogs with NAD. The results indicate different pathway of neuronal loss of these canine neuronal disorders. PMID- 20585193 TI - Molecular MR imaging of cancer gene therapy: ferritin transgene reporter takes the stage. AB - Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation mediated cancer gene therapy using the ferritin reporter gene. PMID- 20585194 TI - Diagnostic value of SPIO-mediated breath-hold, black-blood, fluid-attenuated, inversion recovery (BH-BB-FLAIR) imaging in patients with hepatocellular carcinomas. AB - PURPOSE: We assessed the value of adding a breath-hold, black-blood, fluid attenuated, inversion recovery (BH-BB-FLAIR) sequence with a small motion-probing gradient (b=10 s/mm(2)) using superparamagnetic iron oxide (SPIO) to our present studies that utilize SPIO to detect hepatocellular carcinoma (HCC). We used inversion recovery (IR) in a FLAIR sequence to suppress signals from cysts and a low b-value to suppress vessel signals and provide higher signal to noise than that using high b-value diffusion-weighted imaging. Use of SPIO is expected to reduce the signal in both normal liver parenchyma and in most benign lesions. MATERIALS AND METHODS: In 19 patients, we reviewed 38 HCC nodules diagnosed by CT arterioportography (CTAP) and CT during hepatic arteriography (CTHA). We divided SPIO-mediated images into sets, those obtained with and without BH-BB-FLAIR. Six radiologists individually interpreted the 2 image sets and sorted them by their confidence levels for the presence of HCC, and we calculated the area under the receiver operating characteristic (ROC) curve (Az) for each image set. RESULTS: On images obtained with BH-BB-FLAIR after SPIO administration, 33 of the 38 HCC nodules appeared as areas of high signal and cyst signal was extinguished. The ROC analysis showed significantly higher Az values in the set with BH-BB-FLAIR (0.89) than in the set without (0.83). CONCLUSIONS: Adding BH-BB-FLAIR to existing SPIO-mediated imaging protocols improved detection of HCC nodules and added only 24 s to the scan time. PMID- 20585195 TI - Correlation between estimated glomerular filtration rate (eGFR) and apparent diffusion coefficient (ADC) values of the kidneys. AB - PURPOSE: Study of the kidney by apparent diffusion coefficient (ADC) measurements is interesting because of the organ's high blood flow and water transport functions. We investigated the relationship between ADC values of the kidney and the estimated glomerular filtration rate (eGFR). METHODS: We retrospectively evaluated 180 patients (113 men, 67 women, aged 20 to 89 years, mean age, 61.06 years) who underwent abdominal magnetic resonance (MR) imaging at 1.5 tesla. Transverse multisection echo-planar diffusion-weighted imaging (DWI) was performed using diffusion gradient b-values of 50 and 1000 s/mm(2). Regions of interests (ROIs) were manually delineated in the parenchyma as large as possible at the level of the middle portion of the bilateral kidneys. For each kidney, 2 nonoverlapping ROIs were placed at different locations; 4 total ROIs from the bilateral kidneys were averaged for each patient. ADC values were measured directly from the ROIs. The eGFR was calculated by an equation based on serum creatinine level. The patients were divided into 3 groups: eGFR<30 mL/min/1.73 m(2); 30<==eGFR<60; and 60<==eGFR. RESULTS: The mean ADC values of the 3 groups were 1.71+/-0.18 for the group with eGFR<30 mL/min/1.73 m(2); 1.87+/-0.11 for those with eGFR>or=30; and 1.88+/-0.12x10(-3) mm(2)/s for those with eGFR>or=60. The mean ADC values were significantly lower in the patients with eGFR<30 than in the other groups (P<0.05); no difference was found between the other groups; and there was no statistically significant correlation between mean ADC and eGFR values. CONCLUSION: Patients with low eGFR tended to have lower ADC values. However, this study failed to show significant correlation between mean ADC values and eGFR. PMID- 20585196 TI - Signal alteration of the cochlear perilymph on 3 different sequences after intratympanic Gd-DTPA administration at 3 tesla: comparison of 3D-FLAIR, 3D-T1 weighted imaging, and 3D-CISS. AB - PURPOSE: Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) imaging after intratympanic gadolinium injection is useful for pathophysiologic and morphologic analysis of the inner ear. However, statistical analysis of differences in inner ear signal intensity among 3D-FLAIR and other sequences has not been reported. We evaluated the signal intensity of cochlear fluid on each of 3D-FLAIR, 3D-T(1)-weighted imaging (T(1)WI), and 3D-constructive interference in the steady state (CISS) to clarify the differences in contrast effect among these 3 sequences using intratympanic gadolinium injection. METHODS: Twenty-one patients underwent 3D-FLAIR, 3D-T(1)WI, and 3D-CISS imaging at 3 tesla 24 hours after intratympanic injection of gadolinium. We determined regions of interest of the cochleae (C) and medulla oblongata (M) on each image, evaluated the signal intensity ratio between C and M (CM ratio), and determined the ratio of cochlear signal intensity of the injected side to that of the non-injected side (contrast value). RESULTS: The CM ratio of the injected side (3.00+/-1.31, range, 0.53 to 4.88, on 3D-FLAIR; 0.83+/-0.30, range, 0.36 to 1.58 on 3D-T(1)WI) was significantly higher than that of the non-injected side (0.52+/-0.14, range, 0.30 to 0.76 on 3D-FLAIR; 0.49+/-0.11, range, 0.30 to 0.71 on 3D-T(1)WI) on 3D-FLAIR and 3D-T(1)WI (P<0.001), although no significant difference was observed on 3D CISS (10.03+/-2.19, range, 5.19 to 14.98, on the injected side; 9.52+/-1.63 range, 7.48 to 13.48, on the non-injected side) (P=0.11). The mean contrast value on 3D-FLAIR (5.93+/-2.57, range, 1.22 to 11.05) was significantly higher than that on 3D-T(1)WI (1.73+/-0.60, range, 0.98 to 3.09) (P<0.001). CONCLUSION: The 3D-FLAIR sequence is the most sensitive for observing alteration in inner ear fluid signal after intratympanic gadolinium injection. Our results warrant use of 3D-FLAIR as a sensitive imaging technique to clarify the pathological and morphological mechanisms of disorders of the inner ear. PMID- 20585197 TI - Increased sensitivity to low concentration gadolinium contrast by optimized heavily T2-weighted 3D-FLAIR to visualize endolymphatic space. AB - PURPOSE: To increase the sensitivity of 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) to low concentration gadolinium (Gd)-based contrast medium, we optimized sequence parameters on a phantom and evaluated the optimized sequence in patients suspicious for endolymphatic hydrops. MATERIALS AND METHODS: All scans were performed on a 3-tesla magnetic resonance (MR) unit using a 32 channel head coil. We optimized sequence parameters using a phantom filled with diluted Gd and compared the optimized protocol with 3D-FLAIR using conventional turbo spin echo sequence (3D-FLAIR-CONV). Nine patients underwent scanning using the newly optimized sequence and 3D-FLAIR-CONV 4 hours after double-dose administration of intravenous Gd. We subjectively scored separation of endo- and perilymph space and measured contrast-to-noise ratio (CNR) between endo- and perilymph. RESULTS: The optimized sequence in the phantom study consisted of: repetition time, 9000 ms; echo time, 540 ms; inversion time, 2400 ms; low constant readout flip angle, 120 degrees in the later part of the echo train. Image contrast became heavily T(2)-weighted (hT(2)W-3D-FLAIR). In patients, we recognized endolymphatic space for both the cochlea and vestibule significantly better by hT(2)W-3D-FLAIR than 3D-FLAIR-CONV (P<0.01). The mean CNR of the new method was also better than that of 3D-FLAIR-CONV (P<0.01). CONCLUSIONS: The newly optimized hT(2)W-3D-FLAIR was more sensitive than the previous method to low concentration of Gd. Visualization of the endolymphatic space by double-dose administration of intravenous Gd would be more reliable using hT(2)W-3D-FLAIR. PMID- 20585198 TI - Intrapelvic chronic expanding hematoma: magnetic resonance imaging findings with pathological correlation. AB - Chronic expanding hematoma is rare and occasionally misdiagnosed as malignant neoplasm. We describe a case in the female pelvis and correlate findings from pathology and magnetic resonance imaging. On diffusion-weighted images (DWI), our patient's hematoma showed 2 different signal intensities, which corresponded to pathological features of fresh and altered blood components. DWI can distinguish between such pathological features of a chronic expanding hematoma. PMID- 20585199 TI - Dual gradient-echo in-phase and opposed-phase magnetic resonance imaging to evaluate lipomatous metaplasia in patients with old myocardial infarction. AB - We present an alternative method for evaluating cardiac fat tissue-dual gradient echo in-phase and opposed-phase magnetic resonance imaging (IPOP-MRI) with electrocardiographic (ECG) gating. Conventional IPOP-MRI can be used to evaluate small amounts of fat and is widely used for abdominal imaging, but cardiac motion artifacts make its use difficult for cardiac imaging. Using ECG gating prior to IPOP-MRI, we evaluated lipomatous metaplasia after myocardial infarction. The areas of lipomatous metaplasia measured by IPOP-MRI with ECG gating correlated well with those areas on black-blood T(1)-weighted imaging (r=0.82, P<0.0001, mean bias-0.29 cm(2), limit of agreement+/-2.06 cm(2)). PMID- 20585200 TI - Callosal and diffuse white matter lesions with restricted water diffusion in hemophagocytic syndrome. AB - We present magnetic resonance (MR) imaging findings of the brain of a 6-year-old girl with fatal hemophagocytic syndrome (HPS); diffusion-weighted imaging shows abnormal intensity in the white matter and entire corpus callosum. HPS is a rare disorder that affects the mononuclear phagocyte system and not uncommonly involves the central nervous system. Various MR imaging findings of HPS have been reported, but restricted water diffusion throughout the entire corpus callosum lesion and lesions of the white matter have not been reported. PMID- 20585201 TI - Decreased number of circulating endothelial progenitor cells in patients with Graves' hyperthyroidism. AB - OBJECTIVE: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves' hyperthyroidism (GD), in whom an increased oxidative stress was observed. DESIGN AND METHODS: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL- 18, monocyte chemoattractant protein-1, tumor necrosis facotr- alpha, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzymelinked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. RESULTS: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p<0.05) compared to NC. Moreover, a reduced number of EPC was observed in patients with GD compared to NC (p<0.05) which turned to NC values after restoring euthyroidism. CONCLUSION: Patients with GD showed a reduction in the physiological protective mechanisms against endothelial damage, probably induced by increased inflammation and oxidative stress. PMID- 20585202 TI - Pediatric endocrine screening for von Hippel-Lindau disease: benefits and the challenge of compliance. AB - Fifteen children and adolescents (4 male) with a median age of 5.4 yr (range 1.2 13.6 yr) were entered into a screening protocol to identify lesions of von Hippel Lindau (VHL) disease. Fourteen had an affected first-degree relative and one had a previous VHL lesion. Screening during the period of 2000 to 2008 followed published guidelines and consisted of measurement of urinary catecholamines, adrenal and renal imaging and ophthalmological and central nervous system examinations and imaging. Screening identified 8 VHL lesions in 6 asymptomatic patients with confirmed genetic mutations. Five patients had elevated urinary noradrenaline excretion and in each case the presence of a pheochromocytoma was identified on adrenal magnetic resonance imagin scan. In one patient a left-sided tumor was identified 1 yr after a right-sided tumor had been removed. In a sixth patient a retinal capillary hemangioma and a cerebellar hemangioblastoma were identified. Patient compliance with the screening protocol was variable reflecting its time-intensive nature. A formal screening programme for this at risk population of pediatric patients, despite being intensive, can identify VHL lesions during a pre-morbid phase and may thus have a beneficial impact on prognosis in this serious disorder. PMID- 20585203 TI - Growth factors, adiponectin, leptin and body mass index in pre-pubertal children born large for gestational age. AB - OBJECTIVE: To examine whether the IGF axis in pre-pubertal children born large for gestational age (LGA) differs from that of those born appropriate for gestational age (AGA). RESEARCH DESIGN AND METHODS: The study population consisted of 98 non-obese children aged 5.5-8 yr, of whom 37 were LGA, with birth weight (BW) > 90th percentile, and 61 AGA. The LGA children were subdivided into two subgroups, with BW 90th-97th percentile (no.=24) and BW > 97th percentile (no.=13), respectively. Total and free IGF-I, their binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), leptin, adiponectin, fasting glucose (GF) and insulin (IF) were measured, and the homeostasis model assessment for insulin resistance (HOMA IR index) was determined. RESULTS: IGF-I, free IGF-I and IGFBP-1 were similar in both groups. Both LGA subgroups had lower IGFBP-3 levels than the AGA group (2.34 +/- 0.61 and 2.70 +/- 0.90, respectively, vs 3.92 +/- 1.1 MUg/ml, p < 0.01). Adiponectin was higher in the 90th-97th percentile LGA subgroup than the AGA group (p<0.01). GF and IF were higher in the LGA group (86.5 +/- 5.6 mg/dl, p < 0.01, and 5.84 +/- 2.13 MUU/ml, respectively, p < 0.05) than in the AGA group (82.6 +/- 7.7 mg/dl and 4.62 +/- 1.9 MUU/ml, respectively), as was the HOMA-IR index (1.27 +/- 0.60 vs 0.94 +/- 0.43, p < 0.01). These three parameters were also found higher in the >97th percentile LGA subgroup. CONCLUSION: The IGF axis was not different in pre-pubertal children born LGA or AGA, with the exception of IGFBP-3, which was lower in the LGA children. In LGA pre-pubertal children the severity of intrauterine overgrowth was associated with the insulin resistance indices. PMID- 20585204 TI - Acylated ghrelin levels in pre-pubertal obese children at diagnosis and after weight reduction: effect of oral glucose ingestion. AB - BACKGROUND: Ghrelin isoforms are involved in energy homeostasis and carbohydrate metabolism. AIM: To determine the influence of oral glucose ingestion and weight reduction on acylated ghrelin (AG) serum levels and on the AG to total ghrelin (TG) ratio (AG/TGr) in obese pre-pubertal children. SUBJECTS AND METHODS: Seventy obese children were studied at diagnosis (D) and after reduction of their body mass index (BMI) of over 1 (-1; no.=51) and 2 SD score (-2; no.=21). Body composition was analyzed and serum levels of glucose, insulin, TG and AG, and the AG/TGr were determined at every time-point in an oral glucose tolerance test (OGTT) at D and at -2. The control group consisted of 32 lean children. RESULTS: At D AG and TG levels were lower in obese children and negatively correlated with BMI. TG levels were negatively correlated with the homeostasis model assessment (HOMA) index in the whole cohort, as with the body fat content (BFC) in the obese patients. Weight loss exclusively reduced BFC and improved HOMA, increasing AG transiently and TG sustainedly, with AG/TGr exclusively decreasing at -2. Glucose ingestion caused a sustained increase in AG and decrease in TG, thus increasing the AG/TGr throughout the entire OGTT; this remained unaltered after weight reduction. CONCLUSIONS: TG and AG levels are influenced by BMI, showing an impairment in childhood obesity that can be improved through weight loss. The different fractions of ghrelin appear to play different roles in carbohydrate metabolism and the calculation of AG/TGr could be useful in the follow up of childhood obesity. PMID- 20585205 TI - A question of identity: should white uniforms be standard for hospital-based RNs? PMID- 20585206 TI - Patient education to reduce elective labor inductions. AB - PURPOSE: To reduce elective inductions among nulliparous women in a community hospital by adding standardized education regarding induction risks to prepared childbirth classes. STUDY DESIGN AND METHODS: Elective induction rates were compared between class attendees and nonattendees before and after the standardized content was added to prepared childbirth classes. A survey of nulliparous women's decisions regarding elective induction was conducted. RESULTS: Elective induction rates of 3,337 nulliparous women were evaluated over a 14-month period (n = 1,694, 7 months before adding content to classes; n = 1,643, 7 months after). Rates did not differ between class attendees (35.2%, n = 301) and nonattendees (37.2%, n = 312, p = .37) before the content was included. However, after standardized education was added, class attendees were less likely to have elective induction (27.9%, n = 239) than nonattendees (37%, n = 292, p < .00). Sixty-three percent of women who attended the classes and did not have elective induction indicated that the classes were influential in their decision. Physicians offered the option of elective induction to 69.5% (n = 937) of survey participants. This was a factor in women's decisions; 43.2% (n = 404) of those offered the option had elective induction, whereas 90.8% (n = 374) of those not offered the option did not have elective induction. CLINICAL IMPLICATIONS: Education regarding elective induction offered during prepared childbirth classes was associated with a decreased rate among nulliparous women who attended classes when compared to those who did not attend. Patient education may be beneficial in reducing elective inductions. PMID- 20585208 TI - Oral intake during labor: a review of the evidence. AB - The purpose of this article is to review evidence and practices within and beyond the United States related to the practice of maternal fasting during labor. Fasting in labor became standard policy in the United States after findings of a 1946 study suggested that pulmonary aspiration during general anesthesia was an avoidable risk. Today general anesthesia is rarely used in childbirth and its associated maternal mortality usually results from difficulty in intubation. Healthcare professionals have debated the risks and benefits of restricting oral intake during labor for decades, and practice varies internationally. Research from the United States, Australia, and Europe suggests that oral intake may be beneficial, and adverse events associated with oral intake such as vomiting and prolongation of labor do not seem to be associated with alterations in maternal or infant outcomes. The World Health Organization recommends that healthcare providers should not interfere in women's eating and drinking during labor when no risk factors are evident. Nurses in intrapartum settings are encouraged to work in multidisciplinary teams to revise policies that are unnecessarily restrictive regarding oral intake during labor among low-risk women. PMID- 20585210 TI - Impact of intimate partner violence on maternal child health. AB - This article synthesizes research that has examined the impact of abuse on women, fetuses, and developing children. Intimate partner violence affects the lives of millions of women, sometimes in ways we have yet to understand. Despite the research in this area, the full impact of abuse on the long-term physical and psychosocial well-being of women and their families is not fully understood. There are data, however, that suggest that lifelong health changes may be linked to patterns of abuse. Intimate partner violence during pregnancy has an impact on not only the woman but the developing fetus and the extended family. It is essential that all women be screened for intimate partner violence, and that nurses understand interventions that have been shown to be effective for this group of patients. PMID- 20585211 TI - Don't miss preconception care opportunities for adolescents. AB - PURPOSE: To examine pregnant adolescents' desire for pregnancy and determine whether there were opportunities for preconception care for pregnant adolescents with desired pregnancies. STUDY DESIGN: Retrospective chart review in a federally funded, urban adolescent care clinic. Medical records for 108 pregnant women under the age of 19 were the sample. A logistic regression model was developed to determine whether desiring pregnancy was associated with a lack of clinic visits before conception. For those adolescents who desired pregnancy and did have previous visits, preconception risks were identified. RESULTS: Of the 33% of adolescents who responded that their pregnancy was desired now or sooner, 18.5% arrived at the clinic already pregnant with no previous care, whereas 81.5% had at least one previous visit at this clinic. Those who desired pregnancy and did have previous visits had a multitude of risk factors present that could have been addressed with preconception counseling (including smoking, drugs, interpersonal violence, and weight issues). The majority of these adolescents had not desired a pregnancy at the time of pregnancy diagnosis; 57.4% of those had one or more documented visits at the clinic before receiving a pregnancy diagnosis. CLINICAL IMPLICATIONS: Nurses who provide care to adolescents have an opportunity to discuss future pregnancies and to use healthcare visits to teach about preconception health. Teaching adolescents who both express a desire for pregnancy and those who do not express such a desire is an important part of comprehensive nursing care. Teens require thorough teaching about healthcare risks such as smoking cessation, body weight control, interpersonal violence, and the need for folic acid. Adolescents should be prime recipients of preconception education at every healthcare visit. PMID- 20585212 TI - Nursing care for postpartum depression, part 1: do nurses think they should offer both screening and counseling? AB - PURPOSE: To assess nurses' views of a nursing model in which nurses screen and also treat new mothers who exhibit symptoms of depression. STUDY DESIGN AND METHODS: This is Part 1 of this descriptive survey (Part 2 in MCN 35(5)), in which nurses (n = 520) completed a statewide survey assessing nurses' views of a model of nursing care that both screens and treats postpartum depression. RESULTS: The majority "strongly agreed" or "agreed" with the statement "having nurses screen for depression using a brief screening tool is a good idea." Most (67.1%) chose the Ob-Gyn Clinic as the appropriate site for such screening. Regarding treatment by nurses, the vast majority of nurses (93.7%) "agreed" or "strongly agreed" with the statement "nurse-delivered counseling with mildly depressed women is a good idea." Almost one half of the nurses already regularly provided some form of counseling, and approximately three quarters were willing to participate in a counseling skills training program. Less than 1.0% (n = 3) indicated that nurse-delivered counseling should not be implemented. The most frequently chosen setting for a nurse-delivered counseling program was home visits (70.6%, n = 367). CLINICAL IMPLICATIONS: Our results indicate nurse delivered screening and treatment of postpartum women is overwhelmingly supported by this segment of U.S. nursing professionals, and indeed, is already occurring in many instances. Nurses who have frequent contact with women during the perinatal period are well positioned to provide screening and treatment for postpartum depression. To implement the two-part U.K. model (both screening and treatment), it is necessary to develop educational programs for staff and patients, and establish screening and treatment protocols as well as referral resources for those with such a need. PMID- 20585213 TI - Perspectives of college students on their childhood ADHD. AB - PURPOSE: To determine what successful young adults perceive was helpful to them when they were struggling with their attention-deficit hyperactivity disorder (ADHD) symptoms as children. STUDY DESIGN AND METHODS: Sixteen young adult college students with a history of ADHD participated in semistructured interviews that asked them which people and what strategies they had found most helpful to them during their childhood. Data were analyzed -using content analysis. RESULTS: The most helpful people were parents and teachers; the most helpful strategies were caring behaviors and active teaching/learning strategies. Participants remembered helpful people as "giving me strategies to help me keep my mind focused on something; keep me involved, keep me interested." CLINICAL IMPLICATIONS: Children with ADHD need the support of caring adults who use active teaching strategies. Nurses working with children and adolescents in any setting can educate parents about the best ways to help children with ADHD succeed, using some of the results of this research. PMID- 20585214 TI - Spirituality as a coping resource for African American parents of chronically ill children. AB - PURPOSE: To examine spirituality as a coping resource for a sample of African American parents who have a child with a chronic condition. STUDY DESIGN AND METHODS: Descriptive correlation design with a sample of 168 African American parents. Parents completed a demographic questionnaire, the Coping Health Inventory for Parents (CHIP), the Family Crisis Oriented Personal Evaluation Scale (F-COPES), and the spirituality subscale of the Functional Assessment of Chronic Illness Therapy Measurement System (FACIT-Sp-12). Data were analyzed with frequency distributions and Pearson product moment correlations. RESULTS: Most frequently reported positive coping patterns included "believing in God," "doing things with my children," "believing that my child is getting the best medical care," and "having faith in God." Most frequent coping resources included "having faith in God," "seeking information from the family doctor," and "showing that we are strong." Results revealed a significant positive correlation between positive parental coping patterns and spirituality. CLINICAL IMPLICATIONS: It is important for nurses to recognize ethnic and cultural aspects of coping and spirituality, and design and implement care measures that support spirituality among families with a child with special healthcare needs. PMID- 20585216 TI - What is computer literacy? PMID- 20585215 TI - The Mediterranean diet: a family affair. PMID- 20585218 TI - The International Year of the Nurse. PMID- 20585219 TI - Thromboprophylaxis for cesarean birth. PMID- 20585220 TI - PRISMA. PMID- 20585221 TI - Subsequent childbirth after a previous traumatic birth. AB - BACKGROUND: Nine percent of new mothers in the United States who participated in the Listening to Mothers II Postpartum Survey screened positive for meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for posttraumatic stress disorder after childbirth. Women who have had a traumatic birth experience report fewer subsequent children and a longer length of time before their second baby. Childbirth-related posttraumatic stress disorder impacts couples' physical relationship, communication, conflict, emotions, and bonding with their children. OBJECTIVE: The purpose of this study was to describe the meaning of women's experiences of a subsequent childbirth after a previous traumatic birth. METHODS: Phenomenology was the research design used. An international sample of 35 women participated in this Internet study. Women were asked, "Please describe in as much detail as you can remember your subsequent pregnancy, labor, and delivery following your previous traumatic birth." Colaizzi's phenomenological data analysis approach was used to analyze the stories of the 35 women. RESULTS: Data analysis yielded four themes: (a) riding the turbulent wave of panic during pregnancy; (b) strategizing: attempts to reclaim their body and complete the journey to motherhood; (c) bringing reverence to the birthing process and empowering women; and (d) still elusive: the longed-for healing birth experience. DISCUSSION: Subsequent childbirth after a previous birth trauma has the potential to either heal or retraumatize women. During pregnancy, women need permission and encouragement to grieve their prior traumatic births to help remove the burden of their invisible pain. PMID- 20585222 TI - Supplementing relaxation and music for pain after surgery. AB - BACKGROUND: Most postoperative patients have unrelieved pain despite the use of patient-controlled analgesia. Nurses need additional effective modalities. Relaxation and music (RM), in addition to analgesics, have been shown to reduce pain more than do analgesics alone. OBJECTIVES: The objectives of the study were to test an intervention of patient teaching for pain management (PT) and compare it with RM for immediate and general effects on postoperative pain. METHODS: Patients having abdominal surgery and receiving patient-controlled analgesia aged 18-75 years (n = 517) were randomized to four groups: PT, RM, a combination (PTRM), and a control. A 2 x 2 factorial design was used to assess PT-Effects and RM-Effects. Immediate effects on pain were measured on visual analogue sensation and distress scales before and after five 20-min tests in the first 2 days. Because participants also listened independently, general nonimmediate effects were examined at eight other times. RESULTS: Using multivariate analysis of covariance with contrasts and pretest control, immediate RM-Effects on pain were found at Day 1 a.m. (p < .001), Day 1 p.m. (p = .04), and Day 2 a.m. (p = .04). No PT-Effects or nonimmediate RM-Effects were found. DISCUSSION: Patient teaching did not result in less pain and did not support the theoretical proposition that PT reduces pain. However, the immediate RM-Effects supported the proposition that nonpharmacological adjuvants to analgesics can ease pain without adding side effects. PMID- 20585223 TI - The Active Balance Childhood program for improving coping and quality of life in Chinese American children. AB - BACKGROUND: Interventions to teach children healthy and effective coping skills could help reduce their risk of becoming overweight. However, few studies have examined whether an intervention that teaches coping strategies in weight management can influence children's coping behavior and psychosocial well-being. OBJECTIVE: The purpose of this study was to examine the efficacy of an interactive, a child-centered, and a family-based program in promoting effective coping, behavioral health, and quality of life in Chinese American children. METHODS: This study used a randomized controlled study of behavioral intervention in 67 Chinese American children (ages 8-10 years, normal weight and overweight) and their families. At baseline and 2, 6, and 8 months after baseline, children had anthropometric measurements and completed questionnaires related to coping skills and quality of life, and parents completed the Child Behavior Checklist. RESULTS: Children in the intervention group reported using more active coping strategies and having a higher quality of life in the physical and emotional health domains than did children in the control group during the 8-month study. Children's behavioral problems did not differ between the intervention and the control groups. Changes in coping and psychosocial well-being were not related to change in body mass index in the entire group, except increased body mass index is associated with decreased emotional quality of life. DISCUSSION: This culturally appropriate behavioral intervention was effective in promoting healthy coping and in improving quality of life in Chinese American children. Its utility for both optimal weight and overweight children suggests potential application of the intervention in a broad range of populations. PMID- 20585224 TI - Exploratory analysis of exercise adherence patterns with sedentary pregnant women. AB - BACKGROUND: It is not well understood how sedentary women who wish to engage in regular exercise adhere to interventions during pregnancy and what factors may influence adherence over time. OBJECTIVE: The aim of this study was to examine longitudinal patterns of pregnant women's adherence to exercise. METHODS: Exploratory secondary data analyses were carried out with 124 previously sedentary pregnant women (ages 31 +/- 5 years; 85% non-Hispanic White) from a randomized controlled trial. Daily exercise logs (n = 92) from 18 through 35 weeks of gestation were explored using linear regression, functional data, and principal component analyses. RESULTS: Adherence decreased as gestation week increased (p < .001). The top adherers maintained levels of adherence, and the bottom adherers decreased levels of adherence. And adherence pattern was influenced by types of exercise throughout the study period. DISCUSSION: Exercise behavior patterns were explored in a randomized controlled trial study, using chronometric data on exercise attendance. A new analytic approach revealed that sedentary pregnant women may adopt exercise habits differently from other populations. PMID- 20585225 TI - The use of interviews in Q methodology: card content analysis. AB - BACKGROUND: Although much has been published in the literature on how to perform a Q methodological study, the use of interviews within this process has received little attention. APPROACH: The purpose of this review is to explore the use of interviews in a Q methodological study. RESULTS: An introduction to Q methodology is provided. The aims of an interview within a Q methodological study are described, and how these aims lend themselves to a particular method of analysis is explored. How to perform this analysis is outlined. DISCUSSION: The use of interviews can increase the validity of a Q methodological study by providing the participant's rationale for analysis of the factor arrays. When to perform the interviews is still under debate, and further study is required to determine whether the timing affects the results. PMID- 20585226 TI - An application of longitudinal analysis with skewed outcomes. AB - BACKGROUND: Longitudinal designs are indispensable to the study of change in outcomes over time and have an important role in health, social, and behavioral sciences. However, these designs present statistical challenges particularly related to accounting for the variance and covariance of the repeated measurements on the same participants and to modeling outcomes that are not normally distributed. OBJECTIVES: The purpose of this study was to introduce a general methodology for longitudinal designs to address these statistical challenges and to present an example of an analysis conducted with data collected in a randomized clinical trial. In this example, the outcome of interest-monthly health-related out-of-pocket expenses incurred by breast cancer survivors-had a skewed distribution. METHODS: Common statistical approaches are for longitudinal analysis using linear and generalized linear mixed models are reviewed, and the discussed methods are applied to analyze monthly health-related out-of-pocket expenses. DISCUSSION: Although standard statistical software is available to conduct longitudinal analyses, training is necessary to understand and to take advantage of the various options available for model fitting. However, knowledge of the basics of the methodology allows assimilation and incorporation into practice of evidence from the numerous studies that use these designs. PMID- 20585227 TI - Self-induced vomiting as a probable mechanism of an isolated hyoid bone fracture. AB - Fractures of the laryngeal skeleton (hyoid bone and thyroid horns) are an important finding in a forensic autopsy because they are almost always caused by significant trauma and often are relevant in determining the cause and manner of death. In the forensic setting, these injuries are seen in some hangings and more frequently in manual strangulation. Less common mechanisms include direct blows, "choke holds," and hyperextension of the neck. We present a case of a 37-year-old woman who died of complications of acute ethanol intoxication. The case involves an incidental hyoid bone fracture unrelated to the cause of death as well as facial petechiae. After review of all of the medical records, autopsy findings and scene/police investigations-the key findings of facial petechial hemorrhages and hyoid bone fracture are best attributed to the mechanism of self-induced vomiting. This case emphasizes the importance of synthesizing autopsy findings with the patient's medical and social history to avoid unnecessary investigation or prosecution. This is the second known case of this novel mechanism of hyoid bone fracture in the medical literature and the first in the forensic literature. PMID- 20585228 TI - Reduction in Purkinje fiber number in rats undergone fatal electrocution. AB - Purkinje fibers in cardiac conduction tissue during fatal electrocution. A total of 16 Sprague Dawley rats were divided into 2 groups as follows: the electrocution group and the control group.Animals were deeply anesthetized with sodium pentobarbital and, in the electrocution group, all 8 rats underwent a fatal electrical shock (220 v,50 Hz) followed by cervical dislocation. In the control group, all 8 rats underwent execution by cervical dislocation. Following death, hearts were rapidly excised and perfused with 1% paraformaldehyde before tissues of the left ventricular anterior wall (LVAW) were isolated. The microscopic structure of the Purkinje fibers were subsequently analyzed using conventional hematoxylin and eosin staining. A majority of the Purkinje fibers were located in groups among the cardiac muscle of the LVAW. A significant reduction in Purkinje fiber expression was displayed in the electrocution group compared with the control group (P G 0.05).The mean total number of Purkinje fibers for the electrocution and control groups were 59 T 11 and 3287 T 19 cells, respectively (P G 0.05).The estimated number of Purkinje fibers in the LVAW of the control group was significantly greater than observed in the electrocution group(41.09 T 0.24 vs. 0.7375 T 0.14, P G 0.05). The findings of the current study suggest that such a reduction would be reflected in abnormal cardiac conduction and a possible cause of sudden death. PMID- 20585229 TI - The distribution of the perforators in the anterolateral thigh and the utility of multidetector row computed tomography angiography in preoperative planning. AB - This prospective study searches for the clinical relevance of preoperative multidetector row computed tomography (MDCT) angiography (CTA) for anterolateral thigh (ALT) free flap.Preoperative CTA data were collected in 100 patients between November 2004 and April 2008, and data from 139 limbs were evaluated for the number, type, and location of the ALT perforators. This information was used as operative roadmap and correlated with intraoperative findings in 58 patients.The MDCT revealed an average number of perforators of 2.28 per unilateral ALT (range, 0-4) and projected that 23% of the limb have at least 1 septocutaneous perforator. When the reference line connecting the anterior superior iliac spine ASIS and patella was divided into 10 equal parts, most of the perforators were concentrated in 4/10 to 7/10 and the most common was on the proximal 5/10. Two-thirds of septocutaneous perforators were present in the proximal half. Fifty-two of 58 patients had operative findings consistent with CTA, but 4 perforators failed to appear in preoperative CTA and 3 musculocutanenous perforators were initially identified as septocutaneous type but actually had a short intramuscular course.Preoperative mapping using MDCT angiography is fast, simple, and provides fairly accurate information about the location, type, and the course of the perforators. It allows appropriate selection of the sizable perforator with the shortest intramuscular course preoperatively leading to safer and easier operation with optimal outcome. PMID- 20585230 TI - Chest wall reconstruction in a pediatric patient with ectopia cordis. AB - Ectopia cordis is defined as a congenital malposition of the heart outside of the thoracic cavity. It is a rare condition, and complete ectopia cordis can be a fatal condition. Successful surgical reconstruction of this defect has been reported but is uncommon. The general approach to reconstructing the chest wall involves repositioning the heart and providing adequate coverage of the chest wall defect. We describe our experience with a patient who had complete thoracic ectopia cordis treated with staged chest wall reconstruction. The first stage involved temporary closure with synthetic material, and the second stage involved definitive reconstruction with autologous bone and cartilage grafts supported with plates. The patient has been active and without complaints since the second stage and is awaiting tracheal decannulation. There have been a few descriptions of how to approach chest wall reconstruction in patients with ectopia cordis. The 2 stage method described can be considered to repair the chest wall defect in complete thoracic ectopia cordis. PMID- 20585231 TI - Paraspinous muscle flap reconstruction of complex midline back wounds: Risk factors and postreconstruction complications. AB - With increasingly complex spine surgeries now being performed on a more comorbid patient population, the reconstruction of midline back wounds from these procedures is becoming a frequent dilemma encountered by plastic surgery. The purpose of this study is to examine the effect of various preoperative risk factors on postoperative wound healing complications after paraspinous muscle flap reconstruction of midline back defects. An Institutional Review Board approved, 11-year, retrospective, office and hospital chart review was conducted. All adult patients who underwent paraspinous muscle flap reconstruction during the study period were included. There were 92 patients in the study, representing the largest reported series to-date for the paraspinous muscle flap procedure. Mean follow-up was 120 days. Several wound-healing risk factors were present in this patient population: 72% were malnourished, 41% had hypertension, 37% were obese, 34% had a history of smoking, 32% had diabetes, 16% were on chronic steroids, 14% had a history of more than 2 previous spine surgeries, and 9% had a history of radiation to the wound area. Factors significantly (P < 0.05) associated with postreconstruction wound complications included history of traumatic spine injury, prereconstruction hardware removal, a history of more than 2 spine surgeries, hypertension, and lumbar wound location. This patient population possesses multiple comorbidities making complex wound healing difficult. Several specific risk factors are associated with an increased rate of postreconstruction wound complications after paraspinous muscle flaps. The paraspinous muscle flap remains an important tool for spinal wound reconstruction in the reconstructive surgeon's armamentarium. PMID- 20585232 TI - The role of antibiotics in reduction mammaplasty. AB - This prospective study was conducted to assess the influence of antibiotics use on surgical site infections (SSI) rates after reduction mammaplasty. Patients undergoing reduction mammaplasty were assigned to group 1 (n = 50), which received intravenous cephalotin pre- and postoperatively, besides oral cephalexin for 6 days after discharge, or to group 2 (n = 50), which received no antibiotics. Patients were followed up weekly for 30 days, regarding to SSI, by a blinded surgeon. The Centers for Disease Control and Prevention definitions and classification of SSI were adopted. There was no statistical difference between the groups in regard to age, body mass index, duration of operation, and total resection weight. SSI rates were 2% and 14% in groups 1 and 2, respectively (P = 0.03). In group 2, older patients and those with higher resection weight had significant higher SSI rates (P = 0.02 and P = 0.04, respectively). We observed that antibiotics use decreased SSI rates after reduction mammaplasty. PMID- 20585233 TI - Effect of mesenchymal stem cells on skin graft to flap prefabrication: an experimental study. AB - Angiogenetic potential has been reported for bone marrow-derived stem cells (BSCs) and adipose-derived stem cells (ASCs). The superficial femoral artery, vein, and fascia were used as a vascular crane for prefabrication model of skin graft to flap. BSCs or ASCs were injected before the adaptation of the graft to the vascular crane depending on the group. The prefabricated grafts were then transferred to inguinal region in every 7 days to observe the viability. In experiment part I (n = 18), the critical time for the prefabrication was found to be 1 week. In experiment part II (n = 12), the control and experiment assays were performed on the same animal to support the data of the experiment part I. The viability of flaps was evaluated. The vascular density was higher in BSC, and ASC groups. The Vascular Endothelial Growth Factor immunohistochemical staining was quantified. Furthermore, mesenchymal stem cells could be helpful in any prefabrication procedure in which neovascularization is indispensable. PMID- 20585234 TI - An analysis of the bacterial flora found in the external auditory canals of microtia patients: results and clinical applications. AB - During the process of auricular reconstruction in cases of microtia patients with external auditory canals (EAC), bacterial contamination from the EAC can cause cartilage infection. In this article, we retrospectively analyzed the data on bacterial flora present in the EAC of these patients.Preoperatively, in 91 microtia patients, culture samples were obtained, and isolates were tested for in vitro susceptibility to antibiotics. One hundred volunteers with no ear abnormalities were also evaluated as part of the control group.Seventy-nine specimens in 91 microtia patients showed growth of bacteria (86.8%): a total of 97 organisms were isolated. Dominating bacteria were of the staphylococci species (85.6%). Fourteen Staphylococcus isolates were resistant to methicillin. The percentage of microtia patients showing a presence of methicillin-resistant staphylococci isolates (15%) was significantly higher than the percentage in the "normal" volunteer group showing a presence of methicillin-resistant staphylococci isolates (2%; P = 0.0009).To decrease the complications that occurred due to cartilage infection during auricular reconstruction in the cases of microtia with EAC, we suggest that bacterial floras of the EAC be routinely examined and the patients be treated with appropriate antibiotics preoperatively. PMID- 20585235 TI - Pretreatment with octreotide modulates iNOS gene expression, mimics surgical delay, and improves flap survival. AB - We aimed to evaluate the role of a synthetic somatostatin analogue in delay procedure of experimental skin flaps. Thirty-six rats were randomly divided into 2 groups of 18 each to compare the possible local ischemic effect of octreotide with that of surgical delay in the dorsal random pattern skin flap model. The inducible nitric oxide synthase gene expression was assessed in the flap territory at intervals of immediate, 24 and 48 hours after preconditioning. Histologic analysis was performed in rats at 48th hour and 3 additional rats were used for microangiography. A gradual increase of daily transcript levels was detected in both groups (P < 0.05). The differences of molecular and histologic findings between the groups were not distinctive. Pharmacologically preconditioned rat displayed relevant microvascular features. Forty rats were further grouped randomly into 4 groups of 10 each. In group 1 rats, flaps were raised and reinserted without any prior intervention. Group 2 rats underwent surgical delay procedure, whereas flap territories of the others received either saline solution or octreotide 1 week before the ultimate flap harvest. After another 7-day period, both delay procedures were found effective in improving flap viability (P < 0.01). Ischemia induced by octreotide favored to investigate its utility in delay phenomenon. Although it was not as effective as the surgical delay procedure, it may be a safe pharmacologic alternative to improve the flap survival. PMID- 20585236 TI - A double-blind controlled trial of polyglytone 6211 versus poliglecaprone 25 for use in body contouring. AB - The use of absorbable sutures to obtain secure dermal closure in surgeries such as body contouring is common. The risk of complications based on the absorption rate of these materials is unknown. This study attempts to determine whether a faster absorbing suture material such as polyglytone 6211 will lead to fewer complications such as extrusion and granuloma formation as compared with less rapidly absorbing materials such as poliglecaprone 25. Concomitantly, this study also attempts to explore the possible negative outcomes that may be due to faster loss of strength, such as dehiscence and poor scar aesthetics. We found that extrusion occurs less frequently with the rapidly absorbed polyglytone 6211 suture material, without increase in granuloma formation, infection, dehiscence, cellulitis, necrosis, seroma formation, and hematoma formation. We also observed no clinical difference in the cosmetic appearance of scars at the 12-week postoperative follow-up visit. PMID- 20585237 TI - Melatonin ameliorates doxorubicin-induced skin necrosis in rats. AB - Doxorubicin (DXR), a highly effective chemotherapeutic agent, causes serious injury when extravasated. The injury can sometimes result in skin necrosis and ulceration, requiring surgery. The detrimental effect of DXR on the antioxidant system via free oxygen radicals is one of the mechanisms proposed in its etiology. Thus, we used melatonin, a potent antioxidant, and compared the effects with dimethylsulfoxide (DMSO), which is used in the treatment of patients with DXR-induced extravasation.Twenty-seven Wistar-albino rats were used. After intradermal injection of DXR, DMSO was injected into the extravasated area and melatonin was given intraperitoneally. On day 14 of the experiment, skin ulcers were clearly formed and samples were taken with a punch biopsy. Ulcer sizes were measured. Tissue samples were analyzed for superoxide dismutase, glutathione peroxidase, and malondialdehyde enzymes, and histopathologically evaluated.Melatonin clearly decreased MDA levels, ulcer size, and histopathologic ulcer scores in DXR extravasated tissue. DMSO also decreased MDA levels, ulcer size and histopathologic ulcer score. However, melatonin was remarkably more effective than DMSO in terms of antioxidant enzyme activity, oxidative stress, and histopathologic ulcer scores in rats. Necrosis was evident in the DXR-treated group and some slides showed necrosis involving the fascia. Histopathologic ulcer scores of the necrotic tissue decreased in the DMSO and melatonin groups. The ulcer score in the melatonin group was significantly lower than in the control group. Although the ulcer score in the DMSO group was lower than control, there was no statistically significant difference. The ulcer size in the DMSO group was significantly lower than the control group. The ulcer size in the melatonin group was significantly lower than both the DMSO and control groups.We believe that melatonin, either alone or in combination with DMSO, may be used for treating DXR extravasation. In addition, free oxygen radicals play a crucial role in the etiology of the injury, which should be considered in further studies. PMID- 20585238 TI - The German registry for natural orifice translumenal endoscopic surgery: report of the first 551 patients. AB - OBJECTIVE: To analyze patient outcome in the first 14 months of the German natural orifice translumenal endoscopic surgery (NOTES) registry (GNR). SUMMARY BACKGROUND DATA: NOTES is a new surgical concept, which permits scarless intra abdominal operations through natural orifices, such as the mouth, vagina, rectum, or urethra. The GNR was established as a nationwide outcome database to allow the monitoring and safe introduction of this technique in Germany. METHODS: The GNR was designed as a voluntary database with online access. All surgeons in Germany who performed NOTES procedures were requested to participate in the registry. The GNR recorded demographical and therapy data as well as data on the postoperative course. RESULTS: A total of 572 target organs were operated in 551 patients. Cholecystectomies accounted for 85.3% of all NOTES procedures. All procedures were performed in female patients using transvaginal hybrid technique. Complications occurred in 3.1% of all patients, conversions to laparoscopy or open surgery in 4.9%. In cholecystectomies, institutional case volume, obesity, and age had substantial effect on conversion rate, operation length, and length of hospital stay, but no effect on complications. CONCLUSIONS: Despite the fact that NOTES has just recently been introduced, the technique has already gained considerable clinical application. Transvaginal hybrid NOTES cholecystectomy is a practicable and safe alternative to laparoscopic resection even in obese or older patients. PMID- 20585239 TI - Trends in surgery for Crohn's disease in the era of infliximab. AB - OBJECTIVE: To examine the use of surgical procedures for Crohn's disease since the introduction of infliximab. SUMMARY BACKGROUND DATA: Prior studies have shown that the overall rate of surgery for Crohn's disease has not changed significantly since the introduction of infliximab, an immunomodulator considered particularly effective in treating Crohn's fistulas. How infliximab has affected individual rates of specific types of procedures, particularly surgery for intestinal fistulas, is unknown. METHODS: We used the Nationwide Inpatient Sample to identify all hospital admissions for Crohn's disease for each year from 1993 through 2004. Cases of Crohn's disease and relevant surgical interventions were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Using US Census data to establish population denominators, trends in population-based rates of use of these procedures were examined over time. Trends were tested for significance with Spearman rank correlation tests. RESULTS: From 1993 to 2004, there was no statistically significant change in population-based rates of small bowel and right colon resection, while rates of left colon resection, other colon resection, and rectal resection declined moderately. However, rates of surgical repair of fistulas of the small intestine, the most commonly performed fistula operation, increased by 60%, from 1.5 per 1,000,000 in 1993 to 2.4 per 1,000,000 in 2004 (P = 0.04). CONCLUSIONS: During the period of adoption of infliximab as a novel treatment for Crohn's disease, overall rates of bowel resections have either remained relatively stable or decreased moderately, while rates of small bowel fistula repair have increased significantly. These findings call into question the effectiveness of infliximab in preventing the need for surgery for Crohn's disease at the population level. PMID- 20585240 TI - Cholecystokinin/Cholecystokinin-1 receptor-mediated peripheral activation of the afferent vagus by enteral nutrients attenuates inflammation in rats. AB - OBJECTIVE: The current study investigates activation of the nutritional anti inflammatory pathway by lipid-rich nutrition. BACKGROUND: Enteral nutrition activates humoral and neural pathways to regulate food intake and sustain energy balance. Recently, we demonstrated that enteral nutrition and in particular lipid rich nutrition modulates inflammation and prevents organ damage. METHODS: Male rats were fasted or fed lipid-rich nutrition before hemorrhagic shock. Disruption of afferent vagal fibers with capsaicin (deafferentation) was used to investigate involvement of afferent fibers. Peripheral activation of afferent vagal fibers via cholecystokinin (CCK)-mediated activation of CCK-1 receptors was investigated using administration of the selectively peripheral acting CCK-1 receptor antagonist, A70104 and PEGylated-CCK9. Tissue and blood were collected 90 minutes after shock to assess systemic inflammation and intestinal integrity. RESULTS: Deafferentation reversed the inhibitory effect of lipid-rich nutrition on systemic levels of tumor necrosis factor-alpha and interleukin-6, and on intestinal leakage of horseradish peroxidase and bacterial translocation. Furthermore, the protective effects of lipid-rich nutrition were negated by A70104, indicating that lipid-rich nutrition triggers peripheral CCK-1 receptors on vagal afferents to modulate inflammation. These findings were substantiated by the fact that pretreatment of fasted rats with PEGylated-CCK9, which acts on peripheral CCK-1 receptors, attenuated systemic inflammation, and loss of intestinal integrity. CONCLUSION: These data demonstrate that enteral lipid-rich nutrition modulates inflammation and preserves intestinal integrity via CCK release which activates CCK-1 receptors located on afferent vagal fibers. Taken together, the current study reveals a novel gut-brain-immune axis and provides new insight into the applicability of enteral nutrition to treat inflammatory conditions. PMID- 20585241 TI - Pharmacologic treatment of anaphylaxis: can the evidence base be strengthened? AB - PURPOSE OF REVIEW: To evaluate the evidence base for the pharmacologic treatment of anaphylaxis. RECENT FINDINGS: In this review, we focus on four classes of medications (the alpha/beta-agonist epinephrine (adrenaline), H1-antihistamines, H2-antihistamines, and glucocorticoids) that are used in healthcare settings for the initial treatment of anaphylaxis. Epinephrine and many H1-antihistamines and glucocorticoids were introduced before the era of randomized controlled trials and before the era of evidence-based medicine. In anaphylaxis, no randomized controlled trials that are free from methodological problems and meet current standards have been performed with these medications, or with H2-antihistamines. The evidence base for epinephrine injection is stronger than the evidence base for use of other medications in anaphylaxis. Guidelines unanimously recommend prompt injection of epinephrine as the life-saving first-line medication in anaphylaxis; however, they differ in their recommendations for H1-antihistamines, H2-antihistamines, and glucocorticoids. Epinephrine is the only medication that is universally available for anaphylaxis treatment in healthcare settings worldwide. Paradoxically, it is underused in anaphylaxis treatment. SUMMARY: For ethical reasons, there should never be a placebo-controlled trial of epinephrine in anaphylaxis. We discuss why the possibility of conducting randomized placebo controlled trials with H1-antihistamines, H2-antihistamines, and particularly with glucocorticoids in anaphylaxis should be considered in order to improve the evidence base for treatment and guide clinical decision-making. We also describe the precautions that will be needed if randomized controlled trials are conducted in anaphylaxis. PMID- 20585242 TI - Recent advances in antileukotriene therapy. AB - PURPOSE OF REVIEW: Despite profound effects of leukotrienes in experimental models, clinical responses to antileukotriene drugs are highly heterogeneous. This review discusses recent advances concerning the molecular mechanisms of antileukotrienes as well as their efficacy in various clinical scenarios and patient groups. RECENT FINDINGS: Appreciation of the role of leukotriene E4 and the existence of its distinct receptors may explain the limited efficacy of current leukotriene receptor antagonists. Pharmacogenetic studies highlight the influence of several leukotriene pathway genes on clinical responsiveness. Benefits of addition of antileukotrienes to inhaled corticosteroids in chronic adult asthmatics have been shown, but their role in acute asthma is unclear. Evidence suggests they are not a first-line treatment for allergic rhinitis or urticaria, but may provide useful additional therapy. In children antileukotrienes provide symptomatic benefit in preschool wheezers, but have no clear role in bronchiolitis or acute asthma. Adherence to montelukast appears superior to inhaled corticosteroids. Use in sleep-disordered breathing and eosinophilic gastroenteropathies warrants further investigation. Despite recent concerns thorough analysis of existing data suggests antileukotrienes are well tolerated drugs. The possible link with Churg-Strauss syndrome requires further investigation. SUMMARY: The leukotriene pathway remains an attractive target in asthma and allergic disease, particularly in light of renewed appreciation of the role of leukotriene E4. Clarification of the clinical role of antileukotrienes is needed. PMID- 20585243 TI - Generation of reactive intermediates in photoallergic dermatitis. AB - PURPOSE OF REVIEW: Photosensitivity disorders are cutaneous reactions caused or amplified in their severity by sunlight, normally ultraviolet radiation (UVA or UVB). These reactions appear when xenobiotics are topically or systemically administered, and the individuals are exposed to solar or artificial light. RECENT FINDINGS: Photoallergic reactions seem to be initiated by covalent binding of the photosensitizer to a skin protein, forming adducts capable of interacting with the immune system. The most frequent reactions of this type (photoallergic dermatitis) are induced by drugs and mediated by T cells. Diagnosis of photoallergy requires identification of the responsible agent, which is not always clear-cut. Photopatch testing is the method of choice for definitive diagnosis. SUMMARY: In the current review, some specific examples of photoallergic xenobiotics are given. They include nonsteroidal anti-inflammatory drugs, antibiotics, platelet aggregation inhibitors, and sunscreens. In general, they are taken from the scientific literature published during the last decade, with particular emphasis on the most recent articles. The focus is on the mechanistic aspects, specifically on the generation of reactive intermediates capable of reacting with proteins. PMID- 20585244 TI - Opioid use in chronic noncancer pain: guidelines revisited. AB - PURPOSE OF REVIEW: The treatment of chronic noncancer pain with opioids is controversial. This review aims to find answers to three questions patients and physicians might have: how much (pain relief can be expected), how long (will pain relief be sustained) and how bad (are side-effects)? To this end, we reviewed the second generation of clinical guidelines on this topic. These are based on a significantly higher number of randomized controlled trials than former ones and, therefore, allow evidence-based statements. RECENT FINDINGS: Six guidelines have been launched recently to improve care and safety when treating chronic noncancer pain with opioids. The evidence base for long-term administration of opioids is weak, mostly due to methodological flaws in the available studies and because opioids have no superior effects compared with other analgesics. The maximum pain relief attributable to opioid or nonsteroidal anti-inflammatory drug administration for up to 3 months is 8-12 out of 100 units. It is doubtful that this is clinically important for patients with chronic noncancer pain. Even selected 'responders' from previous randomized controlled trials do not report noticeable pain relief. The small effect-size differences between the classes of analgesic drugs do not provide a basis for differential therapeutic decisions. SUMMARY: Many guideline panels concentrate their recommendations solely on safety of opioid analgesics and patients are usually not informed about the (low) degree of pain relief to be expected. This makes adherence of patients unlikely. Beyond that, multimodal treatment of chronic noncancer pain should become the center of attention. PMID- 20585245 TI - The role of botulinum toxin in management of pain: an evidence-based review. AB - PURPOSE OF REVIEW: In the present review we discuss the role of botulinum neurotoxins (BoNTs) in the management of different pain conditions, with evidence based data on the toxins' efficacy on pain and its mechanisms. RECENT FINDINGS: Experimental in-vitro studies have reported promising results of a novel recombinant chimera of BoNT A and E that inhibits the calcitonin gene-related peptide exocytosis from brainstem sensory neurons. Animal studies in neuropathic pain rat models have reported an analgesic effect of BoNT A given after the neuropathic procedure and a bilateral antinociceptive effect to the unilateral noxious stimuli. There is a growing body of evidence that BoNTs are effective in myofascial pain syndrome, neuropathic pain, and joint pain. The pre-existing evidence that BoNTs are ineffective in migraine or other headache disorders has not yet been challenged. In other pain syndromes, studies published in the last review year have not contributed significantly in either demonstrating or invalidating the research that has so far proved inconclusive. SUMMARY: The role of BoNTs in management of pain is not yet well established. Larger studies in neuropathic pain, joint pain, and myofascial pain syndrome are needed to fully ascertain the role for BoNT therapy in those areas. PMID- 20585246 TI - Standardizing care and monitoring for anesthesia or procedural sedation delivered outside the operating room. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize recommendations for the safe and efficient conductance of sedation and anesthesia at remote locations; and to define safety standards, monitoring techniques, quality of care and procedural eligibility. RECENT FINDINGS: Anesthesia outside of the operating room is rapidly increasing in numbers, which has seen a growth of older and sicker patients. These circumstances have created a need for guidelines, for both specialist anesthesia providers and nonanesthesia-trained practitioners, that define patient selection, minimum monitoring (hemodynamics and respiration), facility design and equipment, policy framework, recovery facilities and policies. The patient's safety throughout all stages of sedation and/or anesthesia is the most pertinent goal. Recent data emphasize the importance of monitoring pulse oximetry and end-tidal carbon dioxide for any sedating or anesthetic procedure. Substandard monitoring combined with oversedation and subsequent respiratory depression are implicated as the main reasons for catastrophic sedation and anesthetic outcomes at remote locations. SUMMARY: Patient selection, procedure appropriateness and location appropriateness are the key elements defining the provision of safe anesthesia care outside the operating room. Titratable, short-acting intravenous drugs are preferred such as propofol and remifentanil. PMID- 20585247 TI - Obesity genes and insulin resistance. AB - PURPOSE OF REVIEW: The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of 'metabolically healthy but obese' (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. RECENT FINDINGS: The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. SUMMARY: Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID- 20585248 TI - Mitochondrial dysfunction in obesity. AB - PURPOSE OF REVIEW: The review highlights recent findings regarding the functions of mitochondria in adipocytes, providing an understanding of their central roles in regulating substrate metabolism, energy expenditure, disposal of reactive oxygen species (ROS), and in the pathophysiology of obesity and insulin resistance, as well as roles in the mechanisms that affect adipogenesis and mature adipocyte function. RECENT FINDINGS: Nutrient excess leads to mitochondrial dysfunction, which in turn leads to obesity-related pathologies, in part due to the harmful effects of ROS. The recent recognition of 'ectopic' brown adipose in humans suggests that this tissue may play an underappreciated role in the control of energy expenditure. Transcription factors, PGC-1alpha and PRDM16, which regulate brown adipogenesis, and members of the TGF-beta superfamily that modulate this process may be important new targets for antiobesity drugs. SUMMARY: Mitochondria play central roles in ATP production, energy expenditure, and disposal of ROS. Excessive energy substrates lead to mitochondrial dysfunction with consequential effects on lipid and glucose metabolism. Adipocytes help to maintain the appropriate balance between energy storage and expenditure and maintaining this balance requires normal mitochondrial function. Many adipokines, including members of the TGF-beta superfamily, and transcriptional coactivators, PGC-1alpha and PRDM16, are important regulators of this process. PMID- 20585249 TI - Molecular neuroendocrine targets for obesity therapy. AB - PURPOSE OF REVIEW: Although energy balance is tightly regulated in order to maintain a specific level of adiposity, the incidence of obesity continues to increase. Consequently, it is essential that effective therapeutics for the treatment and prevention of obesity be developed. This review provides a brief update on some recent advances in the characterization of neuroendocrine targets for obesity therapy. RECENT FINDINGS: During the review period, considerable progress occurred in the understanding of previously described neuroendocrine regulators of energy balance, and several novel targets have been identified. Moreover, the understanding of the neural circuitry and molecular mechanisms of the neuroendocrine regulation of energy homeostasis has been expanded. SUMMARY: Energy balance is maintained by neuroendocrine signals arising from many tissues including the gastrointestinal tract and adipose tissue. These signals are integral to the cessation of meals and to the ability of the brain to monitor energy status and respond accordingly. Many current targets for obesity therapy are based on manipulating the activity of these signals and their receptors; however, to date, clinical-weight loss based on this strategy has been minimal and alternative approaches such as combinatorial therapies are emerging. PMID- 20585250 TI - Impact of laser eustachian tuboplasty on middle ear ventilation, hearing, and tinnitus in chronic tube dysfunction. AB - OBJECTIVES: Long-term Eustachian tube dysfunction (ETD) predisposes to various secondary middle ear diseases. Most surgical and prosthetical interventions on the Eustachian tube itself have proven to be ineffective, whereas middle ear surgeries treat the sequelae of ETD without major influence on the underlying tubal pathology. The purpose of our study was to evaluate the outcome of laser Eustachian tuboplasty (LETP) on tubal function and associated otological symptoms in topically anesthetized ETD patients with intact or perforated eardrums. DESIGN: In a prospective clinical investigation, outpatient LETP was carried out in 31 subjects with therapy-refractory chronic ETD. The study population comprised two groups: 16 patients with mesotympanic eardrum perforations diagnosed with noninflammatory chronic otitis media (COM) and 15 patients with intact eardrums including otitis media with effusion, adhesion processes, and dysfunctional pressure equalization. Clinical examination and data acquisition were performed 2 wks before LETP as well as 8 wks and 1 yr postoperatively. On COM patients, LETP was done at 10-wk intervals before the scheduled tympanoplasty. Assessment of clinical effectiveness was based on transnasal videoendoscopy, ear microscopy, tubal function tests (Valsalva maneuver and passive tubal opening), audio- and tympanometric measurements, and visual analog scales. Tansnasal, fiber-guided laser surgery was performed in contact mode using a semiconductor diode laser (lambda = 830 nm, 4 W). We hypothesized that regulated laser ablation of hyperplastic mucosa at the epipharyngeal dorsal circumference of the tubal ostium could be effective in improving the associated symptoms such as dysfunctional pressure equalization, aural fullness, conductive hearing loss, and tinnitus. RESULTS: LETP resulted in persistent volume reduction of the posterior tubal circumference in all patients. Objective parameters revealed significant improvement of tubal function tests and middle ear ventilation in 62% of subjects after 8 wks (66% after 1 yr). Significant long term reduction of conductive hearing loss was achieved in both patient groups. Besides, tinnitus loudness was significantly reduced in COM subjects after tympanoplasty. Visual analog scales showed very low values for intraoperative pain and discomfort and high scores for long-term overall patient satisfaction as well as improvement of the symptoms such as dysfunctional pressure equalization and aural fullness. Subjects with post-LETP Valsalva feasibility marked higher values for satisfaction and symptom improvement than patients without successful Valsalva maneuver. COM subjects scored higher in hearing improvement and satisfaction after LETP and successful tympanoplasty than patients with intact eardrums. CONCLUSIONS: Outpatient LETP seems to be a suitable, safe, easily applicable, and well-tolerated treatment option before (revision) tympanoplasties and in all investigated diseases developing from long-lasting pathologic middle ear ventilation. Minimally invasive shaping of the hyperplastic nasopharyngeal Eustachian tube under topical anesthesia seems to be effective in improving tubal function as well as the associated symptoms such as dysfunctional pressure equalization, aural fullness, and conductive hearing loss in otherwise therapy refractory chronic ETD. PMID- 20585251 TI - Dynamic sex roles among men who have sex with men and transmissions from primary HIV infection. AB - BACKGROUND: Previous studies estimating the fraction of transmissions from persons with primary HIV have not focused on the effects of switching sex role in male homosexual populations. Such behavioral fluctuations can increase the contribution of primary HIV in the overall population. METHODS: We modeled HIV transmission with 8 compartments defined by 4 behavioral groups, with different anal-insertive and anal-receptive combinations, and 2 stages of infection. We explored the effects of fluctuating behavioral categories on endemic prevalence and the fraction of transmissions from primary HIV. We varied transition rates to develop the theory on how behavioral fluctuation affects infection patterns, and we used the transition rates in a Netherlands cohort to assess overall effects in a real setting. RESULTS: The dynamics of change in behavior-group status over time observed in the Netherlands cohort amplifies the prevalence of infection and the fraction of transmissions from primary HIV, resulting in the highest proportions of transmissions being from people with primary HIV. Fluctuation between dual- or receptive-role periods and no-anal-sex periods mainly determines this amplification. In terms of the total transmissions, the dual-role risk group is dominant. Fluctuation between insertive and receptive roles decreases the fraction of transmissions from primary HIV, but such fluctuation is infrequently observed. CONCLUSION: The fraction of transmissions from primary HIV is considerably raised by fluctuations in insertive and receptive anal sex behaviors. This increase occurs even when primary HIV or later infection status does not influence risk behavior. Thus, it is not simply biology but also behavior patterns and social contexts that determine the fraction of transmissions from primary HIV. Moreover, each primary HIV transmission has a larger population effect than each later infection transmission because the men to whom one transmits from primary HIV carry on more chains of transmissions than the men to whom one transmits later in infection. Reducing transmissions from primary HIV should be a primary focus of HIV control efforts. PMID- 20585253 TI - Estimating pathogen-specific asymptomatic ratios. AB - The asymptomatic ratio (the proportion of asymptomatic infected cases among the total infected cases) is an important indicator in public health. However, symptoms manifested by a case infected with a pathogen may result from infections other than the specific pathogen of interest. When a case is infected with multiple pathogens, it can be difficult to distinguish which pathogen is causing the symptoms. These conditions complicate the estimation of asymptomatic ratios. We used influenza serologic data from Taiwan to test a novel log-linear binomial regression model that estimates pathogen-specific asymptomatic ratios for influenza subtypes. We find that 75% of the H1N1 subtype and 65% of the H3N2 subtype were asymptomatic. Asymptomatic ratios help to quantify the magnitude of asymptomatic persons who may be capable of spreading pathogens to others. PMID- 20585252 TI - Estimating the optimal CD4 count for HIV-infected persons to start antiretroviral therapy. AB - BACKGROUND: Optimal timing of antiretroviral therapy in HIV-infected persons is unclear, although 2 recent large observational studies have improved our understanding of the best CD4 threshold for initiation. These studies compared the effect of starting HAART on mortality and mortality/AIDS between strata defined using broad ranges of CD4 counts. We sought to expand this understanding using a novel statistical approach proposed by Robins et al. METHODS: Using observational data from 1034 antiretroviral-naive HIV-infected patients from Nashville, Tennessee, we directly estimated the optimal CD4 count for initiation of HAART to maximize patient health 6, 12, 24, and 36 months after the first instance of CD4 falling below 750. We measured health using 2 outcome metrics, one based on CD4 counts at the end of follow-up and the other based on a published quality-of-life scale; both metrics incorporated death, AIDS-defining events, serious non-AIDS events, and CD4 at the end of follow-up, if asymptomatic. RESULTS: The CD4-based metric estimated that to maximize health 6, 12, 24, and 36 months after study entry, HAART should be initiated within 3 months of CD4 first dropping below 495 (95% confidence interval [CI] = 468-522), 554 (459-750), 489 (427-750), and 509 (460-750), respectively. The quality-of life-based metric produced CD4 initiation threshold estimates of 337 (95% CI = 201-442), 354 (288-386), 358 (294-750), and 475 (287-750) for the same time points. CONCLUSIONS: Our results support early initiation of antiretroviral therapy, although the criterion for starting therapy depends on the choice of health outcome. PMID- 20585254 TI - Gestational age, birth weight, and risk for injuries in childhood. AB - BACKGROUND: Some children experience more injuries than others due to personal or environmental risk factors, or to chance. Most injury studies have focused on proximal causes; few have examined the role of neonatal characteristics such as birth weight and gestational age. METHODS: We carried out a population-based cohort study of 1,524,114 singletons born in Denmark between 1 January 1978 and 31 December 2004. We obtained information on gestational age, birth weight, and injury from the Danish Medical Birth Registry and the National Hospital Register. We followed participants up to age 29 years and estimated the incidence rate ratio (IRR) of hospitalization for injury, using Poisson regression models. RESULTS: The risk of injury throughout childhood (mainly before 12 years of age) increased with decreasing gestational age and birth weight. The IRR of injury in the first 12 years of life was 4.2 (95% CI = 3.5-5.1), 2.3 (2.0-2.5), and 1.5 (1.3-1.6), respectively, for children born at gestational weeks 20-32, 33-36, and 37-38, compared with those born at gestational weeks 39-41. The IRR was 4.0 (3.4 4.6), 2.5 (2.1-2.8), and 1.4 (1.3-1.6) for children with a birth weight less than 2000 g, 2000-2499 g, and 2500-2999 g, compared with children of 3000-3999 g. Birth weight was also associated with increased risks of injury after adjusting for gestational age. CONCLUSIONS: Children born with adverse neonatal conditions have a marked increased risk of injury. This suggests an opportunity to identify children who may benefit from injury prevention. More research is needed to identify the causal pathways driving these associations. PMID- 20585255 TI - Changes in residential proximity to road traffic and the risk of death from coronary heart disease. AB - BACKGROUND: Residential proximity to road traffic is associated with increased coronary heart disease (CHD) morbidity and mortality. It is unknown, however, whether changes in residential proximity to traffic could alter the risk of CHD mortality. METHODS: We used a population-based cohort study with a 5-year exposure period and a 4-year follow-up period to explore the association between changes in residential proximity to road traffic and the risk of CHD mortality. The cohort comprised all residents aged 45-85 years who resided in metropolitan Vancouver during the exposure period and without known CHD at baseline (n = 450,283). Residential proximity to traffic was estimated using a geographic information system. CHD deaths during the follow-up period were identified using provincial death registration database. The data were analyzed using logistic regression. RESULTS: Compared with the subjects consistently living away from road traffic (>150 m from a highway or >50 m from a major road) during the 9-year study period, those consistently living close to traffic (90%) did not require anaesthetic airway management despite an overall acute scan diagnosis rate of around 25% and 30 day mortality of 10%. PMID- 20585258 TI - Epidemiological review and proposed management of 'scaphoid' injury in children. AB - BACKGROUND: The epidemiology and optimal management of injury to the paediatric scaphoid (carpal navicular) is unknown.The objective of this study is to evaluate these parameters in the Emergency Department of a tertiary children's hospital. METHODS: A retrospective study of a 12-month period of all children attending a single Paediatric Emergency Department who underwent plain radiography of the scaphoid bone. RESULTS: One hundred and seventeen children (aged 8-12 years inclusive) were included (0.4% of all attendances). On the initial plain radiographs, 17 children showed definite or suspected fractures. At follow-up, only 12 had confirmed fractures. All these children had fallen onto their outstretched hand. Only one patient with normal plain radiographs at presentation was subsequently diagnosed with a scaphoid fracture. All healed without evidence of avascular necrosis. CONCLUSION: Pain in the anatomical snuff box is a poor indicator of bone injury to the scaphoid of any sort. Scaphoid fracture is a rare injury in childhood and from this study, it is extremely unlikely to occur under the age of 9 years.The actual bone pathology of an injured paediatric scaphoid may not be clear, but these children have significant pain and tenderness. Further studies are warranted to improve the diagnostic process and the management of paediatric scaphoid injury. PMID- 20585259 TI - A roadmap for CAHPS: what home health organizations need to know. PMID- 20585260 TI - Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and tenofovir in healthy subjects. AB - BACKGROUND: The potential for a drug interaction between S/GSK1349572 and tenofovir disoproxil fumarate (TDF) was evaluated in an open-label, repeat dose, 3-period, drug-drug interaction study in healthy subjects. METHODS: S/GSK1349572 was administered at 50 mg once daily for 5 days (period 1) followed by a 6-day washout period. TDF 300 mg once daily was then administered for 7 days (period 2). The combination of S/GSK1349572 and TDF was then coadministered for 5 days (period 3). Pharmacokinetic parameters were determined and compared between periods. RESULTS: Fifteen subjects completed all periods and follow-up. S/GSK1349572 and TDF were generally well tolerated with few adverse events reported. No clinically significant trends in post-dose laboratory abnormalities, vital signs, or electrocardiogram values were noted. Pharmacokinetic parameters of S/GSK1349572 and tenofovir during combination therapy were similar to those when given alone, demonstrating no significant drug interaction. S/GSK1349572 geometric least squares mean ratios (90% confidence interval) for AUC(0-tau), Cmax, and Ctau were 1.01 (0.908, 1.11), 0.969 (0.867, 1.08), and 0.920 (0.816, 1.04), respectively. Tenofovir geometric least squares mean ratios (90% confidence interval) for AUC(0-tau), Cmax, and Ctau were 1.12 (1.01, 1.24), 1.09 (0.974, 1.23), and 1.19 (1.04, 1.35), respectively. CONCLUSION: S/GSK1349572 and TDF can be coadministered without dose adjustment. PMID- 20585261 TI - Frequent screening for syphilis as part of HIV monitoring increases the detection of early asymptomatic syphilis among HIV-positive homosexual men. AB - BACKGROUND: Syphilis continues to be a significant public health problem among HIV-positive men who have sex with men (MSM) internationally. This study aimed to determine whether the routine inclusion of syphilis serology with every blood test performed as part of HIV monitoring increases the detection of early asymptomatic syphilis among HIV-positive MSM. METHODS: We examined the effect of this intervention, implemented in January 2007, on the detection of early asymptomatic syphilis among HIV-positive MSM attending the Melbourne Sexual Health Centre, Australia, and compared this with the previous clinic policy of annual syphilis screening. RESULTS: In the 18 months before and after the intervention, the median number of syphilis tests performed per man per year was 1 and 2, respectively. The proportion of MSM diagnosed with early syphilis who were asymptomatic was 21% (3 of 14) and 85% (41 of 48) for the 2 respective periods (P = 0.006). The time between the midpoint since last syphilis serology and diagnosis of syphilis was a median of 107 days (range 9-362) and 45 days (range 23-325) for the 2 periods, respectively (P = 0.018). CONCLUSIONS: The inclusion of routine syphilis serology with every blood test performed as part of HIV monitoring in HIV-positive MSM resulted in a large increase in the proportion of men diagnosed with early asymptomatic syphilis. This simple intervention probably also decreased the duration of infectiousness, enhancing syphilis control while also reducing morbidity. PMID- 20585263 TI - Increased turnover of FoxP3high regulatory T cells is associated with hyperactivation and disease progression of chronic HIV-1 infection. AB - OBJECTIVES: To characterize the homeostasis of CD4FoxP3 regulatory T cells (Treg) and its association with immune hyperactivation in the disease progression of chronic HIV-1 infection. DESIGN: Treg proliferation and apoptosis markers were determined and the relation to disease progression and Treg activation was analyzed. METHODS: Fifty-six HIV-1-infected highly active antiretroviral therapy (HAART)-naive subjects and 17 HAART-treated subjects were enrolled. Proliferation and apoptosis of Treg from peripheral blood were evaluated by intracellular Ki-67 and active caspase-3 or surface Annexin-V staining. T-cell activation markers, CD38 and HLA-DR, were simultaneously monitored. The effects of in vitro TCR (T cell receptor) stimulation on proliferation, apoptosis, and activation of Treg were determined from both HIV-1-infected subjects and healthy controls. RESULTS: HIV-1-infected patients displayed increased Treg turnover status indicated by higher expression of proliferation marker Ki-67 and apoptosis marker active caspase-3 and Annexin-V. Turnover level of Treg was positively associated with disease progression and immune hyperactivation. In vitro TCR stimulation increased the turnover level of Treg. The HAART treatment decreased the turnover and activation levels of Treg in complete responders. CONCLUSIONS: Turnover level of Treg was increased in HIV-1-infected subjects, which is associated with immune hyperactivation and the disease progression, and may serve as a surrogate marker to predict HIV-1 disease progression. PMID- 20585264 TI - Nonpharmacological treatment of tics in Tourette syndrome adding videotape training to self-hypnosis. AB - OBJECTIVE: This case series examines the practicality of using a standardized method of training children in self-hypnosis (SH) methods to explore its efficiency and short-term efficacy in treating tics in patients with Tourette syndrome. METHODS: The files of 37 children and adolescents with Tourette syndrome referred for SH training were reviewed, yielding 33 patients for analysis. As part of a protocol for SH training, all viewed a videotape series of a boy undergoing SH training for tic control. Improvement in tic control was abstracted from subjective patient report. RESULTS: Seventy-nine percent of the patients trained in this technique experienced short-term clinical response, defined as control over the average 6-week follow-up period. Of the responders, 46% achieved tic control with SH after only 2 sessions and 96% after 3 visits. One patient required 4 visits. CONCLUSIONS: Instruction in SH, aided by the use of videotape training, augments a protocol and probably shortens the time of training in this technique. If SH is made more accessible in this way, it will be a valuable addition to multi-disciplinary management of tic disorders in Tourette syndrome. PMID- 20585262 TI - HIV-1 drug resistance mutations are present in six percent of persons initiating antiretroviral therapy in Lusaka, Zambia. AB - OBJECTIVE: To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008. METHODS: Population sequencing of the HIV-1 pol gene was performed in the PharmAccess African Studies to Evaluate Resistance Monitoring cohort. Drug resistance-associated mutations (DRMs) were identified using the WHO 2009 Surveillance DRM list. Multiple logistic regression was used to assess factors associated with baseline resistance. RESULTS: The overall prevalence of baseline resistance was 5.7% [31 of 548 participants; 95% confidence interval (CI): 3.9 to 7.9]; the prevalence of DRMs associated with nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors was 1.1%, 4.0%, and 1.1%, respectively. Resistance prevalence was 5.2% (27 of 523) in antiretroviral-naive and 16.0% (4 of 25) in antiretroviral-experienced (ie, previous use of ART or antiretroviral prophylaxis for prevention of mother to-child transmission) participants (P = 0.022). Dual-class resistance to NRTIs and NNRTIs was observed in 0.6% of participants. HIV-1 subtype C was identified in 98.0% (537 of 548) of participants. Prior antiretroviral experience (odds ratio: 4.32, CI: 1.34 to 14.0, P = 0.015) and hemoglobin level (highest tertile versus lowest tertile odds ratio: 2.74, CI: 1.09 to 6.89, P = 0.033) were independently associated with baseline resistance. CONCLUSIONS: Baseline resistance may compromise the response to standard NNRTI-based first-line ART in 6% of patients in Lusaka, Zambia. Continuous resistance monitoring is warranted to maintain individual and population-level ART effectiveness. PMID- 20585265 TI - Stress reactivity as a moderator of family stress, physical and mental health, and functional impairment for children with sickle cell disease. AB - OBJECTIVE: To evaluate whether autonomic nervous system (ANS) reactivity modifies the relation between family stress, and physical and mental health, and functional impairment for children with sickle cell disease. METHODS: Thirty eight 5-to 8-year old children with sickle cell disease completed a 20-minute ANS reactivity protocol measuring respiratory sinus arrhythmia and pre-ejection period during comparison and challenge tasks in social, cognitive, sensory, and emotion domains. Domain-specific reactivity was calculated as the difference between challenge and comparison tasks; overall reactivity was calculated across domains as the mean of the difference scores. ANS profile scores combined the overall respiratory sinus arrhythmia and pre-ejection period reactivity scores. Caregivers completed measures of family stress, child physical and mental health symptoms, and functional impairment. RESULTS: Family stress was associated with child functional impairment whereas overall and cognitive ANS reactivity was associated with co-morbid internalizing and externalizing mental health symptoms. Interaction models showed that children with the classic ANS profile (parasympathetic inhibition and sympathetic activation) in the cognitive and emotion domains were most vulnerable to the effects of stress, with more functional impairment and injuries when family stress was high, controlling for age, sex, and parent education. CONCLUSION: The costs to patients and families in diminished quality of life and to the health care system could be reduced by further exploration of strategies to identify children with sickle cell disease who are most vulnerable under conditions of high family stress and heightened psychobiologic reactivity. PMID- 20585266 TI - Child behavior checklist clinical scales discriminate referred youth with autism spectrum disorder: a preliminary study. AB - OBJECTIVE: To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. METHOD: Comparisons were made between children with ASDs (n = 65) with intelligence quotient >70 and children without ASDs (N = 83) on the clinical scales of the Child Behavior Checklist. Stepwise logistic regression was used to identify those scales that best predicted ASDs when compared with the non-ASD comparison group. Receiver operating characteristic curves examined the ability of the significant predictor T-scores to identify ASDs versus the non-ASD subjects. RESULTS: Withdrawn, Social Problems, and Thought Problems T-scores were the best independent predictors of ASD status. The Withdrawn + Social + Thought Problems T-scores yielded an area under the curve of 0.86, indicating an 86% chance that a randomly selected sample of ASD subject will have abnormal scores on these scales than a randomly selected sample of non-ASD subjects. CONCLUSION: These findings suggest that a new Child Behavior Checklist-ASD profile consisting of the Child Behavior Checklist-Withdrawn, Social, and Thought Problems scales could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ASDs in the clinical setting. PMID- 20585267 TI - Can state early intervention programs meet the increased demand of children suspected of having autism spectrum disorders? AB - OBJECTIVE: To determine whether Early Intervention programs have the capacity to accommodate the expected increase in referrals following the American Academy of Pediatrics' 2007 recommendation for universal screening of 18- and 24-month-old children for Autism Spectrum Disorders (ASD). METHOD: We conducted a telephone survey of all state and territory early. Intervention coordinators about the demand for ASD evaluations, services, and program capacity. We used multivariate models to examine state-level factors associated with the capacity to serve children with ASD. RESULTS: Fifty-two of the 57 coordinators (91%) responded to the survey. Most states reported an increase in demand for ASD-related evaluations (65%) and services (58%) since 2007. In addition, 46% reported that their current capacity poses a challenge to meeting the 45-day time limit for creating the Individualized Family Service Plan. Many states reported that they have shortages of ASD-related personnel, including behavioral therapists (89%), speech-language pathologists (82%), and occupational therapists (79%). Among states that reported the number of service hours (n = 34) 44% indicated that children with ASD receive 5 or fewer weekly service hours. Multivariate models showed that states with a higher percentage of African-American and Latino children were more likely to have provider shortages whereas states with higher population densities were more likely to offer a greater number of service hours. CONCLUSION: Many Early Intervention programs may not have the capability to address the expected increase in demand for ASD services. Early Intervention programs will likely need enhanced resources to provide all children with suspected ASD with appropriate evaluations and services. PMID- 20585268 TI - Practice parameters and financial factors impacting developmental-behavioral pediatrics. AB - OBJECTIVE: Little has been published about the professional activities of developmental-behavioral (DB) pediatricians. To better understand the settings in which DB pediatricians work, allocation of their professional time, and how financial considerations impact their practice, the Society for Developmental and Behavioral Pediatrics surveyed its membership. METHOD: An extensive on-line three part survey was conducted in 2006-2007 assessing sociodemographic characteristics, practice descriptors, coding and billing practices, productivity goals and perceived pressures among Society for Developmental and Behavioral Pediatric's 438 physician members. RESULTS: Of the pediatricians responding, representing all regions of the United States, 93% were DB pediatrics subspecialty board certified or eligible. The majority was practicing DB pediatrics full-time (73%); and 67% were exclusively in academic settings. All reported seeing patients, 84% reported teaching, 76% reported having administrative responsibilities, and 46% reported conducting research. Despite having non-clinical responsibilities, full-time equivalent positions included an average of 25 hours per week in direct patient care and 14.5 hours per week (37% of clinical time) in indirect patient care. Only 42% reported working with multidisciplinary teams. Salaries varied widely within and across regions. Deficits in billing/coding practices, awareness of personal clinical productivity, and familiarity with national productivity benchmarks were identified. CONCLUSIONS: DB pediatricians work in diverse settings nationwide. They provide considerable time in indirect patient care, which is poorly reimbursed in general and relative to direct patient care. The results of this survey offer opportunities for provider, institutional and payer education. PMID- 20585269 TI - The effects of multisystemic therapy on family support for weight loss among obese African-American adolescents: findings from a randomized controlled trial. AB - OBJECTIVE: To determine whether multisystemic therapy, an intensive, home- and community-based intervention, could increase family support for healthy eating and exercise in obese African-American adolescents. Relationships between changes in family support, weight status, and body fat composition at the end of the trial were also evaluated. METHOD: A pilot randomized clinical trial was conducted with 49 obese adolescents (body mass index > or = 95th %ile). Participants were randomized to receive multisystemic therapy or Shapedown, a group weight loss intervention. Participants received treatment for 6 months. Data were collected at baseline and 7-month posttest (i.e., treatment termination). Changes in family support for healthy eating and exercise were assessed by self-report questionnaire. Bivariate analyses were used to assess the relationship between change in family support during the trial and youth body mass index, percent overweight, and body fat composition at follow-up. RESULTS: Participation in multisystemic therapy was associated with significantly greater improvements in family encouragement for healthy eating and family participation in exercise and greater decreases in discouraging behavior from family members than Shapedown participation. Increases in family participation in exercise were significantly related to lower youth body mass index, percent overweight, and body fat composition at follow-up. CONCLUSIONS: Intensive, home- and community based treatment increased family support for health behavior changes among obese minority adolescents, and these changes were directly related to weight status. Such health improvements are important for the well-being of a subset of youth who are at high risk for future health complications. PMID- 20585270 TI - Acral cutaneous melanoma in a Spanish Caucasian population. AB - Acral lentiginous melanoma (ALM) is the most frequent type of cutaneous melanoma in the Asian and African populations, but the fourth distinct variant of cutaneous melanoma in the Caucasian population. Histological criteria and prognosis of ALM remain controversial. A retrospective study, showing epidemiological, clinical, histological and survival characteristics of melanomas located on acral sites (acral cutaneous melanoma) compared with nonacral melanomas. Fifty-two of 552 melanomas (9.42%) were located on acral sites. Histological examination revealed ALMs in 30 cases (61%), nodular melanomas in seven cases (14.3%) and superficial spreading melanomas in five cases (10.2%). Patients with ulcerated melanomas had an older mean age (62.3 vs. 57.2 years) (P=0.02). Tumour thickness was greater in acral melanomas (2.8 vs. 1.9 mm) (P=0.039). Overall survival and disease-free survival did not differ significantly from melanomas on other sites. Acral cutaneous melanoma has peculiar epidemiological features in the Spanish population. They are more frequent in patients above 65 years of age and they have a greater tumour thickness, but they are not significantly associated with a lower survival. PMID- 20585271 TI - Clinical and therapeutic impact of 18F-FDG PET/CT whole-body acquisition including lower limbs in patients with malignant melanoma. AB - OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients. PMID- 20585272 TI - Unnecessary imaging, not hospital distance, or transportation mode impacts delays in the transfer of injured children. AB - OBJECTIVES: Timely transfer of injured children to pediatric trauma centers (PTCs) that can address their unique needs is important. This study was designed to understand the characteristics of transferred injured children. METHODS: Data from our level I PTC over 5 years (2002-2006) were reviewed. Transferred patients were divided based on time from injury to arrival at our PTC: early (<2 hours) and late (>2 hours). Data collected included demographics, Injury Severity Scale score, Glasgow Coma Scale score, mode of transportation, referring hospital information including pretransfer imaging, and disposition from our emergency room. RESULTS: Seven hundred forty-eight patients were included. Eighty-two percent (n = 612) were in the late group and arrived, on average, 6 hours after those transferred early (420 vs 69.9 minutes, P < 0.05). Seventy-nine percent (n = 147) of transfers with severe injuries (Injury Severity Scale score >15) and 47% (n = 15) of those with severe head injuries (Glasgow Coma Scale score <8) arrived late. The disproportionate number of late transfers was consistent among all transferring hospitals regardless of distance and only slightly improved in the group transferred by air ambulance. In addition, those transferred late had significantly more pretransfer imaging (49% vs 23%, P = 0.0025). CONCLUSIONS: Despite the advantages of care in trauma centers, a significant number of severely injured children are transferred well beyond 2 hours after injury. This study has demonstrated that this pattern of delayed transfer is a systemic problem occurring among all transferring hospitals regardless of distance or mode of patient transfer and is associated with increased use of imaging before transfer. PMID- 20585273 TI - Lifetime and age-conditional risk of human immunodeficiency virus diagnosis, Missouri, 1998-2007. AB - Lifetime and age-conditional probabilities of human immunodeficiency virus (HIV) diagnosis risk in Missouri were assessed using cross-sectional HIV diagnosis and mortality rates. An increased lifetime risk of HIV diagnosis was associated with males, blacks, and persons residing in metropolitan areas. The estimates emphasize the disparity in risk by race/ethnicity and area of residence. PMID- 20585274 TI - Comparing HIV partner notification effectiveness between blacks and Hispanics in New York City. AB - Between July 2006 and November 2007, a total of 894 blacks and 491 Hispanics were interviewed to assess partner notification services. Fewer Hispanics needed to be interviewed to identify 1 newly diagnosed partner as compared with blacks (24 vs. 60, P < 0.01), but number needed to be interviewed was similar for identifying partners with any HIV infection. PMID- 20585275 TI - STD screening of HIV-infected MSM in HIV clinics. AB - BACKGROUND: National guidelines for the care of human immunodeficiency virus (HIV)-infected persons recommend asymptomatic routine screening for sexually transmitted diseases (STDs). Our objective was to determine whether providers who care for HIV-infected men who have sex with men (MSM) followed these guidelines. METHODS: We abstracted medical records to evaluate STD screening at 8 large HIV clinics in 6 US cities. We estimated the number of men who had at least one test for syphilis, chlamydia (urethral and/or rectal), or gonorrhea (urethral, rectal, and/or pharyngeal) in 2004, 2005, and 2006. Urethral testing included nucleic acid amplification tests of both urethral swabs and urine. We also calculated the positivity of syphilis, chlamydia, and gonorrhea among screened men. RESULTS: Medical records were abstracted for 1334 HIV-infected MSM who made 14,659 visits from 2004-2006. The annual screening rate for syphilis ranged from 66.0% to 75.8% during 2004-2006. Rectal chlamydia and rectal and pharyngeal gonorrhea annual screening rates ranged from 2.3% to 8.5% despite moderate to high positivity among specimens from asymptomatic patients (3.0%-9.8%) during this period. Annual urethral chlamydia and gonorrhea screening rates were higher than rates for nonurethral sites, but were suboptimal, and ranged from 13.8% to 18.3%. CONCLUSIONS: Most asymptomatic HIV-infected MSM were screened for syphilis, indicating good provider adherence to this screening guideline. Low screening rates for gonorrhea and chlamydia, especially at rectal and pharyngeal sites, suggest that substantial barriers exist for complying with these guidelines. The moderate to high prevalence of asymptomatic chlamydial and gonococcal infections underscores the importance of screening. A range of clinical quality improvement interventions are needed to increase screening, including increasing the awareness of nucleic acid amplification tests for nonurethral screening. PMID- 20585276 TI - Prevalence and correlates of syphilis and condom use among male injection drug users in four Afghan cities. AB - BACKGROUND: : Injecting drug use is increasing in Afghanistan but little is known about sexual risk behaviors and sexually transmitted infection (STI) prevalence among injection drug users (IDU). The purpose of this study is to assess prevalence and correlates of syphilis and condom use with female sex workers (FSWs) among male IDUs in Hirat, Jalalabad, Kabul, and Mazar-i-Sharif, Afghanistan. METHODS: : Participants in this cross-sectional study completed an interviewer-administered questionnaire and serologic testing for syphilis between June 2005 and January 2008. Factors associated with syphilis condom use with FSWs were assessed with site-controlled logistic regression analysis. RESULTS: : Of 1078 male IDUs, most (90.3%) reported prior sexual experience, of whom 27.6% reported any condom use. Sexual experiences with FSWs (58.1%) and men or boys (25.7%) were common, although prior condom use with FSWs (32.6%) or male partners (10.8%) was relatively rare. Few reported having a lifetime STI diagnosis (6.3%, n = 68) or symptoms (10.4%, n = 110) in the last 6 months. Prevalence of syphilis was 3.72% (95% CI: 2.66%-5.06%) and varied significantly between sites ranging from 0% (Jalalabad) to 13.9% (Mazar-i-Sharif) (P < 0.001)). Syphilis was significantly associated with STI diagnosis (adjusted odds ratio [AOR] = 3.84) or sex with FSWs (AOR = 3.82) in the last 6 months, and with lower (<=6 years) educational level (AOR = 2.20). Prior condom use with FSWs was independently associated with living outside Afghanistan in the last decade (AOR = 5.52, 95% CI: 1.83-16.71), higher income (AOR = 2.03, 95% CI: 1.17-3.51), greater number of lifetime partners (AOR = 1.80, 95% CI: 1.32-2.45), and younger age (AOR = 0.985, 95% CI: 0.973-0.998). CONCLUSIONS: : Although prevalence of syphilis and condom use varied significantly by site, high levels of risky sexual behavior were common, and consistent condom use was rare among IDUs in Afghanistan. Harm reduction programming should incorporate sexual risk reduction and condom promotion and distribution in Afghan cities. PMID- 20585277 TI - Prevalence of human immunodeficiency virus testing and high-risk human immunodeficiency virus behavior among 18 to 22 year-old students and nonstudents: results of the National Survey of Family Growth. AB - BACKGROUND: This study characterized human immunodeficiency virus (HIV) testing and high-risk behavior among 18 to 22 year-old college students and nonstudents. METHODS: Data from 18 to 22 year-olds (n = 2007) in Cycle 6 of the National Survey of Family Growth, a nationally representative survey conducted between March 2002 and February 2003, were analyzed using univariate and multivariate methods. RESULTS: The estimated percentage of 18- to 22-year-olds ever tested for HIV excluding during blood donation was 34.2% (95% confidence interval [CI]: 31.6%-36.8%) and was less common among students than nonstudents after adjusting for age, gender, race/ethnicity, and marital status (adjusted OR [odds ratios]: 0.54; 95% CI: 0.40-0.73). The estimated percentage tested during the previous year was 18.1% (95% CI: 16.1%-20.1%), and there was no difference between students and nonstudents (adjusted OR: 0.76; 95% CI: 0.55-1.05). The estimated percentage of 18- to 22-year-olds reporting any high-risk HIV behavior was 37.5% (95% CI: 34.4%-40.5%). Of these, only 28.3% (95% CI: 24.5%-32.0%) had an HIV test within the year before the study, and this did not vary by student status (adjusted OR: 0.91; 95% CI: 0.62-1.35). CONCLUSIONS: More than one-third of this young adult population reported high-risk HIV behavior. Of these, less than one third was tested for HIV during the year before the study. These results indicate that enhanced HIV testing and prevention efforts are needed for students and nonstudents, and that HIV testing in this age group should be monitored over time. PMID- 20585278 TI - Distribution of sexually transmitted diseases and risk factors by work locations among female sex workers in Tijuana, Mexico. AB - BACKGROUND: Sex work is regulated in the Zona Roja (red light district) in Tijuana, Mexico, where HIV and sexually transmitted disease (STD) prevalence is high among female sex workers (FSWs). We examined the spatial distribution of STDs by work venue among FSWs in Tijuana. METHODS: FSWs aged 18 years and older who reported unprotected sex with >= 1 client in the past 2 months underwent testing for HIV, syphilis, gonorrhea, and Chlamydia. HIV/STDs were mapped by venue (i.e., bar, hotel) and Getis-Ord Gi statistics were used to identify geographic hotspots. High-risk venues were then identified using a standardized STD ratio (high risk defined as a ratio >= 1.25). Logistic regression was used to assess correlates of working at a high risk venue. RESULTS: Of 474 FSWs, 176 (36.4%) had at least 1 bacterial sexually transmitted infection (STI); 36 (7.6%) were HIV-positive. Within the Zona Roja, 1 venue was identified as a geographic "hotspot," with a higher than expected number of HIV/STD-positive FSW (P < 0.05) as compared to neighboring venues. Using the STD ratio definition, 11 venues were identified as high-risk; FSWs working in these locations had higher education, were more likely to report always using drugs with sex, and having mostly US clients. They were less likely to be registered FSWs or to live at their work venue. CONCLUSIONS: A relatively few number of sex work venues accounted for a large proportion of the HIV/STI burden among FSWs in Tijuana. Structural interventions that focus on sex work venues could help increase STI diagnosis, prevention, and treatment among FSWs in Tijuana. PMID- 20585279 TI - Xenotransplantation: still a bridge too far? PMID- 20585280 TI - Murine cytomegalovirus infection leads to increased levels of transplant arteriosclerosis in a murine aortic allograft model. AB - INTRODUCTION: Cytomegalovirus infection after heart transplantation is considered as risk factor for the development of transplant arteriosclerosis. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus (MCMV) as a single risk factor on transplant arteriosclerosis in an experimental aortic allograft model. METHODS: Major histocompatibility complex class I-mismatched aortas of C.B10-H2(b)/LilMcdJ donor were transplanted into BALB/c recipients, which were either mock-infected or infected with MCMV (strain Smith) on day 7 and harvested 37 days after transplantation. In one experimental group animals received a daily dose of everolimus to increase the viral load of recipients. Grafts were analyzed by histology, morphometry, and immunofluorescence. Intragraft cytokine mRNA production was analyzed by real-time polymerase chain reaction (PCR), and persistence of cytomegalovirus infection was confirmed by TaqMan PCR. RESULTS: After infection with MCMV, there was significantly more intimal proliferation when compared with uninfected controls (intimal proliferation 83.5%+/-9.6% [MCMV] vs. 43.9%+/-5.1% [MCMV]), indicating that MCMV plays a role in the development of transplant arteriosclerosis. Even after treatment with everolimus, MCMV infection pronounced significantly more intimal proliferation (intimal proliferation 52.5%+/-7.3% [MCMV] vs. 20.2%+/-1.7% [MCMV]). Intragraft mRNA expression showed significantly higher production of CD62E, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 after infection with MCMV. Cellular infiltration revealed significantly more CD4, CD8, and dendritic cells. We could also confirm the presence of MCMV for the duration of the experimental protocol by PCR within the spleen, liver, salivary glands, lung, and the aortic transplant. CONCLUSION: These data suggest that MCMV infection plays an important role in the development of transplant arteriosclerosis. PMID- 20585281 TI - Bloodstream infection after kidney transplantation: epidemiology, microbiology, associated risk factors, and outcome. AB - BACKGROUND: Bloodstream infection (BSI) is associated with both relevant morbidity and mortality rates after kidney transplantation. METHODS: From January 1, 2000 to January 31, 2006, all episodes of BSI were retrospectively assessed through the review of medical records in two tertiary teaching Hospitals in Sao Paulo, Brazil, where 3308 transplant procedures were performed during this period. Contaminants and polymicrobial infections were excluded. The main objectives of the study were to describe clinical and microbiologic aspects of BSI, as well as risk factors for both BSI and mortality from these infections in kidney transplant patients. RESULTS: BSI was detected in 185 patients, with onset after a median of 235 days after transplantation; 62% occurred after 6 months. The primary source of infection was the urinary tract in 37.8%. The most prevalent pathogen overall was Escherichia coli (30.3%). Risk factors for early acquired BSI (first 6 months after transplantation) were acute rejection, ureteric stent placement, and receiving an organ from a deceased donor. For late BSI (after 6 months), associated risk factors were acute rejection, Charlson Comorbidity Score more than or equal to 3, and receiving an organ from a deceased donor. Risk factors related to 30-day mortality were Acute Physiology and Chronic Health Evaluation II Score more than or equal to 20, shock, and respiratory failure. CONCLUSIONS: BSI is most frequently a consequence of urinary tract infection, with a high prevalence of gram-negative bacilli. Severity of disease was the main determinant of 30-day mortality after BSI, and based on the knowledge of risk factors, some interventions are suggested for reducing the rate of BSI after transplantation. PMID- 20585282 TI - Drugs for sexually transmitted infections. PMID- 20585283 TI - Preservation of ovarian function during chemotherapy. PMID- 20585284 TI - In brief: only the name remains the same. PMID- 20585285 TI - A sumatriptan needle-free injection for migraine. PMID- 20585286 TI - Ofatumumab (Arzerra) for CLL. PMID- 20585287 TI - Effects of individualized whole-body vibration on muscle flexibility and mechanical power. AB - AIM: The first purpose of the present study was to assess acute, residual and chronic effects of whole-body vibration on hamstring and lower back flexibility through the application of an individual frequency of vibration. The second purpose was to determine whether the applied vibration intervention over time influences flexibility and reactive strength differently. METHODS: Thirty-four young physically active subjects (19 female and 15 male) were randomly assigned to either a Control or a Vibration Group. Lower back and hamstring flexibility was measured using the Stand and Reach Test. The reactive strength was estimated calculating the power in Drop Jump. RESULTS: During whole-body vibration the relative change in acute flexibility for the Vibration Group (5.30+/-1.67 cm, 284%) reached a level of significance (P=0.038) compared to that of the Control Group (3.14+/-2.11 cm, 84%). Statistically significant differences in residual flexibility between the two groups were found at 6-min after the conclusion of vibration (P=0.034), at which point the Vibration Group showed the maximal relative change to pre-test (6.31+/-3.36 cm, 138%) versus the Control Group (3.06+/-1.87 cm, 20%). Chronic exposure of whole-body vibration did not produce significant changes in flexibility over time (P>0.05), whereas power in the Drop Jump performance of the Vibration Group increased significantly resulting in a benefit of 16% (P=0.019). CONCLUSION: The current study shows that individualized whole-body vibration without superimposing other exercises is an effective method of acutely increasing lower back and hamstring flexibility. Furthermore, the applied individualized whole-body vibration over time influences the reactive strength rather than flexibility. PMID- 20585288 TI - Deltoid muscle fiber characteristics in adolescent and adult wrestlers. AB - AIM: The aim of the present study was to examine the adaptation of myosin heavy chain (MHC) isoforms, capillary density and fiber cross sectional area (CSA) of deltoid muscle in adolescent and adult elite Greco-Roman wrestlers. METHODS: Eighteen Greco-Roman wrestlers were divided into two groups: adolescents included 10 athletes (group A) between 14-18 years of age (15.4+/-1.3 yrs) and adults included 8 athletes (group B) between 20-27 years (23.5+/-2.6 yrs). Histochemical analyses were used to determine the muscle fiber type distribution and the muscle fiber cross sectional area. MHC isoform composition was determined with protein electrophoresis, while capillary density (capillary to fiber ratio and capillaries per mm2) analysis was performed with a-amylase Periodic and Schiff staining. RESULTS: Adolescents demonstrated a significantly higher percentage of type I fibers (P<0.05) and type I fiber area (P<0.05) compared to the adults. The percentage of type IIa fiber area were significantly higher in adult wrestlers (P<0.05). MHC I isoforms was significantly higher in adolescents (P<0.05), whereas the MHC isoforms of IIa and IIx did not differ between groups. The capillary density (mm2) were significantly higher (P<0.05) in adolescents compared to adults. CONCLUSION: Our findings suggest that the observed muscle fiber profile in the deltoid muscle of wrestlers may represent an adaptation based on the mechanical and biochemical demands of the long-term training. Such adaptations are linked to the specific characteristics of the training program, the level and the previous training experience of the wrestlers. PMID- 20585289 TI - Effect of different sprint training regimes on the oxygen delivery-extraction in elite sprinters. AB - AIM: The effects of sprint training regimes of varying distance schedules on the oxygen delivery-extraction relationship were investigated in 15 young (22+/-1 years) healthy males national-level sprinters. METHODS: During one session subjects performed four sprints, in a schedule of increasing distance order (100, 200, 300 and 400 m), and during the other session, in a schedule of decreasing distance order (400, 300, 200, and 100 m). All sprint bouts were performed on a treadmill at a speed of 22 km/h-1, which corresponds to 85% of subjects' maximal speeds. The order of the running sequences during sessions was balanced over subjects. RESULTS: During both sprint schedules, all variables except for oxygen extraction in the incremented training regime, increased significantly from rest to exercise. Training regimes were not different with regard to cardiac output and absolute oxygen uptake. However, the decreasing compared to the increasing scheme was characterized by significantly (P<0.05) higher mean values of heart rate (194.5+/-4.1 185.2+/-5.7 beats/min-1, respectively), oxygen extraction (54.3+/-3.8 and 47.1+/-3.4 mL/L-1, respectively) and lactate (10.6+/-0.5 and 9.2+/-0.7 mmol/L-1, respectively), while stroke volume was significantly (P<0.05) lower (100.4+/-4.5 and 109.7+/-4.4 mL, respectively). CONCLUSION: The present study indicates that in sprinters performing a similar distance at the same speed, but under different training regimes interplay exists between oxygen delivery and extraction, suggesting a link between the type of training scheme and physiological cardiovascular and skeletal muscle metabolic adaptations. This may explain the absence of differences between the conditions in absolute oxygen uptake and peak power output. PMID- 20585290 TI - Oxygen uptake, heart rate and energy expenditure during slideboard routines at different cadence. AB - AIM: Little is known about the physiological response during slideboard exercise (SE). The aim of the present study was to analyse the oxygen uptake (V.O2), the heart rate (HR) and the energy expenditure (EE) during a typical slideboard exercise session and investigate differences on these variables when performing the same choreography at two different cadences (130 e 145 beats per minute - bpm). METHODS: The sample comprised 13 female university students (21,77+/-0,97 years), apparently healthy and physically active, with past training in SE and mastering the technical levels 1 and 2. The subjects performed randomly exercise sessions at 130 bpm and 145 bpm. The ventilatory response was measured by an open air circuit system (COSMED K4b2, Rome, Italy) and HR was measured by a portable monitor (Polar Wireless Double Electrode, Kempele, Finland). HR and V.O2, during SE at 130 bpm, were 179.88+/-834 bpm and 37.95+/-3.71 mL/kg/min respectively. At 145 bpm SE mean values were 182.08+/-9.58 bpm and 39.67+/-3.82 mL/kg/min respectively. EE during 130 bpm exercise was 10.60+/-1.69 kcal/min and at 145 bpm was 10.90+/-1.36 kcal/min. No differences were found between 130 and 145 bpm in none of the variables. We conclude that slideboard exercise cardio respiratory response does not seem affected by the rhythm of execution. Moreover the EE associated with this type of exercise is above the literature reports for other types of group aerobic exercises. PMID- 20585291 TI - Ankle-joint mobility and standing squat posture in elite junior cross-country skiers. A pilot study. AB - AIM: Skating technique in cross-country skiing is a complex multi-joint movement with kinematics comparable to those of the standing squat exercise where any restricted joint mobility in the lower extremity-chain may change the movement pattern. The aim of this pilot study was to investigate the effect of ankle mobility on trunk posture during squat exercise in cross-country skiers. METHODS: Seven elite junior cross-country skiers (age range 17-19 years) performed two different standing squats, one with hands on hips and one with arms extended above the head. The squats were recorded on video and analyzed in selected positions: 90 degrees and maximal knee flexion. Segment angles for shank and trunk were calculated from anatomical references relative to vertical/horizontal orientation in space. Recordings from passive ankle dorsiflexion were correlated with 1) trunk flexion, and 2) angle index (trunk flexion relative to shank angle). RESULTS: Reduced ankle dorsiflexion was moderately associated with increased trunk flexion with hands on hips (r=-0.51 to -0.57), and arms above head (r=-0.61 to -0.64). Further, reduced dorsiflexion was also moderately associated with decreased angle index with hands on hip (r=0.60 to 0.67) but highly associated with decreased angle index with arms above head (r=0.75 to 0.76). CONCLUSION: The results imply that reduced ankle dorsal mobility is related to decreased angle index as well as increased trunk flexion during squat exercise, thus indicating the relevance of good ankle joint mobility for appropriate upper-body posture during squat exercise. PMID- 20585292 TI - Superimposed electrical stimulation decreases maximal grip force. AB - AIM: The purpose of this study was to assess maximal grip force in two conditions of voluntary muscular contraction (MVC) and electrical stimulation superimposed on voluntary muscular contraction (SES) to better understand mechanisms and effectiveness of electrical stimulation of the hand. There is conflicting evidence regarding the effectiveness of electrical stimulation superimposed on voluntary muscular contraction on improving maximal force. Increased knowledge of the physiologic and mechanical effects of electrical stimulation applied during voluntary muscular contraction can lead to refinement of its clinical application. METHODS: Twenty subjects (36+/-13 years; 17 males and 3 females) participated in this study. All subjects were undergoing physical therapy within a hand rehabilitation center. They were instructed to randomly perform three grip determinations in both voluntary muscular contraction and superimposed electrical stimulation conditions to elicit maximal grip force of the unaffected hand. Force was assessed using a handheld dynamometer. Subjective force and contraction were assessed just after sessions as well as pain and discomfort using a visual analogue scale. RESULTS: The mean force values were 22+/-7 kg and 30+/-1 kg for the superimposed electrical stimulation and voluntary muscular contraction conditions, respectively. Analyses of the force measures showed that force was weaker in the superimposed electrical stimulation condition (P<0.001). Patients rated their pain and discomfort at 0+/-0 mm and 4+/-2.9 mm, respectively. CONCLUSION: Maximal grip force is reduced when electrical stimulation is superimposed to voluntary muscular contraction. This result could be explained by unbalanced muscular synergies at the hand due to SES, confirming these synergies as essential to produce maximal grip force. PMID- 20585293 TI - The effects of indoor cycling training in sedentary overweight women. AB - AIM: The aim of this study was to evaluate the body composition and physiological effects in young sedentary overweight women after an indoor cycle training period. METHODS: Fourteen subjects (22.6+/-2.1 yrs; 25-29.9 BMI) were trained for 12 weeks in a specific indoor cycling protocol (ICP) consisting of three sessions/week carried out in a fitness room. Body composition and physiological parameters were taken before the beginning of the study and after 12, 24 and 36 sessions. RESULTS: We observed a reduction of 2.6% and 3.2% in body weight and of 4.3% and 5% in fat mass after 24 and 36 sessions respectively (P<0.05). Lean mass increased by 2.3% and 2.6% respectively after 24 and 36 sessions. Body circumferences diminished in response to ICP. Resting heart rate decreased by 6.5% and 9% respectively after 24 and 36 sessions. After the tenth week, we found a reduction of 11 beats.min-1 in average training heart rate, an increase of 0.5 mL/kg-1.min-1 in average training oxygen uptake and an increase of 8.6 Watts in average power output. Moreover, an increase in cardio-respiratory fitness was observed (37.1+/-4.3 vs. 40.2+/-4.6 mL/kg-1.min-1) after 36 sessions. CONCLUSION: The decrease in body weight, without any restriction on food consumption, and the improvement in cardio-respiratory fitness suggests that ICP may be efficient for losing weight and preventing the increased risk of cardiovascular disease in young overweight women. Indoor cycling can be performed by young sedentary overweight women; however, it is fundamental to formulate training protocols which are intensity and length specific to the fitness level of the participants. PMID- 20585294 TI - Effect of plyometric training on chair-rise, jumping and sprinting performance in three age groups of women. AB - AIM: The main purpose of this study was to investigate the influence of 8-wk periodized plyometric training (PT) on chair-rise, jumping and sprinting performance in three groups of women of different age (40-50; 50-60; 60-70 years). METHODS: This study involved a group of 55 women between the ages of 40 and 70 with no PT experience participating in a gymnastic program and recreational activity that did not involve jumping and who had participated since five years. All tests to determine the values of strength endurance, vertical jumping performance (VJP) and velocity were carried out before (PRE), after (POST) and following 8 weeks of rest (DETRAINING) of the 8 weeks of PT. The performance tests were completed in 3 days. RESULTS: The primary finding of this investigation indicates that low impact PT using moderate volume of jumps produced similar enhancements in the three age groups of women in jumping and chair-rise performance (30 CST) (ranging 15-24 %). There were no enhancements in 10 m-sprint time in any of the age groups. In addition, 8 weeks of detraining following an 8 week PT program resulted in similar decreases in chair-rise and jumping performance in all training groups, whereas no further changes were observed in 10-m sprint time. CONCLUSION: The low impact PT proposed appears to be an optimal stimulus for improving VJP and 30 CST during short-term training periods in untrained middle-aged and elderly women. PMID- 20585295 TI - Growth, maturation, functional capacities and sport-specific skills in 12-13 year old- basketball players. AB - AIM: The influence of maturity status on body size, functional capacities and basketball-specific skills was evaluated and multivariate relationships between domains of variables were examined in 80 male basketball players 12.0-13.9 years. METHODS: Height, body mass and two skinfolds were measured. Stage of pubic hair (PH) was assessed clinically. Functional capacity was assessed with the vertical jump (squat jump, countermovement jump), 2-kg medicine ball throw, hand grip strength, 60-second sit-ups and endurance shuttle run. Performances on four basketball skills were tested: shooting, passing, dribbling and defensive movements. Analysis of covariance with age as the covariate was used to test differences among players by stage of puberty. Associations among body size, adiposity, functional capacities and skills were evaluated with canonical correlation analysis. RESULTS: Maturity status explained a significant portion of variance in body size (F=50.13, P<0.01, h2=057, for height; F=13.47, P<0.01, h2=0.26, for weight). The effect of pubertal status was significant for the jumps and upper limb strength, but not for sit-ups or aerobic endurance. Canonical correlations showed an inverse relationship of height and adiposity with skill tests, and a positive relationship between skills and a combination of abdominal muscular strength (sit-ups) and aerobic endurance. CONCLUSION: Skill appeared to be independent of pubertal status and the tallest group of basketball players did not attain better scores in basketball-specific skill tests. PMID- 20585297 TI - Effects of short-term very low-carbohydrate or conventional diet on strength performance. AB - AIM: Weight reduction strategies usually include diet and regular physical activity. A very low-carbohydrate and high protein diet (VLCD) may be preferred instead of a low energy conventional diet (CONV). The effects of VLCD on strength performance are yet to be understood. Aim of the study is to determine the effects of two different restrictive diets on strength performance. METHODS: Sedentary women were assigned to either a VLCD (<40 g carbohydrate; n=12) or a CONV diet (500 to 800 kcal restrictive; 48%, 22% and 30% from carbohydrate, protein and fat, respectively; n=12). Knee extension isokinetic strength tests (3 yen 15 reps at 60 degrees .s-1, with 90 or 180 s rest interval between sets) were performed prior and after a one week diet period. RESULTS: Both groups reduced body mass (VLCD: -2.6+/-1.0% vs. CONV: -1.9+/-1.3%; P<0.05), with no between diets effect. The sum of the total work in three sets (ATW) was 4850+/-1002 J vs. 4801+/-973 J with 90 s rest interval, and 4812+/-1174 J vs. 4812+/-1210 J with 180 s rest interval, respectively, in the pre vs. post-VLCD period. For CONV, values were 4709+/-729 J vs. 4530+/-996 J with 90 s rest interval, and 4760+/-732 J vs. 4816+/-702 J with 180 s rest interval, respectively, in the pre vs. post CONV treatment. No significant differences were detected in the ATW between groups. CONCLUSION: Short-term hypoenergetic diets, irrespective of the carbohydrate content, seem to reduce significantly body mass, but do not impair acute strength performance. PMID- 20585296 TI - The effect of post-exercise carbohydrate ingestion on inflammatory responses to short time, high-force eccentric exercise. AB - AIM: The aim of this study was to investigate muscle damage and inflammatory response following eccentric exercise as well as the effect of carbohydrate supplement on these responses in untrained men. METHODS: Eighteen healthy untrained men were randomly allocated into two carbohydrate (age 21/33+/-0/7 years) and placebo (age 20/66+/-1/22 years) groups. Forty-five repetitions of eccentric elbow flexion were performed with 90% of one maximum repetition by each subject. The exercises were done as three sets of 15 repetitions with 3 minutes rest between sets. Venous blood samples were obtained at pre-exercise, immediately, 8h, and 24h after exercise. Subjects consumed a 6% carbohydrate or placebo drink immediately following the exercise session, every hour, for 10 hours. RESULTS: CK activities and IL-6 levels were significantly greater than per exercise in immediately, 8 h and 24 h after exercise in both groups (P<0.05). No significant increases was observed in CRP levels immediately, 8 h and 24 h after exercise versus baseline, in both groups (P>0.05), but in 8 h versus immediately after exercise, the augmentation in the carbohydrate group was significant(P<0.05). Blood glucose increased significantly 8 h after exercise versus baseline in both groups (P<0.05). There was significant difference in serum IL-6 between two groups in 8 h and 24 h after exercise (P<0.05) and it was greater in carbohydrate group. There was no significant difference in serum CK, CRP, and glucose between two groups (P>0.05). CONCLUSION: According to results, carbohydrate increased the inflammatory (IL-6) response following resistance exercise, but had no effects on CRP and CK. PMID- 20585298 TI - Effects of the time of day of walking on dietary behaviour, body composition and aerobic fitness in post-menopausal women. AB - AIM: Post-menopause is linked to an increased risk of death from cardiovascular disease. Physical exercise and healthy dietary habits are normally suggested to enhance health. The aim of this study was to verify whether the time of day of walking had different effects on both spontaneous dietary intake and body composition modification in overweight and sedentary post-menopausal women. METHODS: Forty-two sedentary post-menopausal women (53.46+/-3.32 yrs) were recruited. Thirty-three completed the study: 29 were suitable for statistical analysis. Of those, 14 walked in the morning (MG) and 15 in the early evening (EG). Body composition, dietary habits and predicted VO2max were investigated. Food intake was analysed for energy, macronutrients and daily distribution. RESULTS: The Mann-Whitney test showed that according to the time of day of walking there were different fat mass (FM) reductions and dietary behaviour responses. EG reduced FM greater than MG and showed a major increase in morning energy intake (EI). Sub-samples did not differ in total EI, daily macronutrient portioning and daily meals variations. The variation of FM was correlated with that of proteins (r=-0.352), morning EI (r=-0.367) and aerobic performance (r=0.369). Both MG and EG improved their aerobic performance. CONCLUSION: The positive effects of walking on health could be optimised by its evening execution because it could also be linked to spontaneous dietary habit modification. PMID- 20585299 TI - Body mass index as a measure of bone mass. AB - AIM: BMI is an indicator of body composition (BC) and adiposity in particular. This status is the result of good correlations with indirect (e.g. predictive) two- and three-component models predicting body fat. Aim of the study is to measure the direct relation of BMI with total and segmental BC, e.g. of skin, muscle, bone, viscera and adipose tissue. METHODS: BC constituents of 29 white elderly persons (17 females and 12 males, aged 78.1+/-6.9 years) were determined by direct dissection. Correlations and stepwise linear regression analysis with BMI (dependent variable) and all BC constituents (independent variables) were calculated. RESULTS: All tissues dissected indicated a too high unexplained variance except for bone that accounted for 84% of BMI variance in females and 61% in males (P<0.001). No other constituents improved the prediction. CONCLUSION: The BMI cannot be an appropriate adiposity index. The high proportion of unexplained variance between BMI and direct BC constituents limit its use as a whole body and as a segmental BC index. The BMI could be an index for Bone Mass instead. PMID- 20585300 TI - Contrasting effects in anthropometric measures of total fatness and abdominal fat mass following endurance and concurrent endurance and resistance training. AB - An increased total fatness, and especially abdominal fat deposition, is associated with a greater risk for a variety of health problems and metabolic disturbances. It is commonly accepted that endurance training induces the greatest alterations in total adiposity despite resistance training possibly having other advantages on body fat distribution. Thirty-seven males were assigned to 16 weeks of endurance training (ET) (N=12), concurrent endurance and resistance training (CT) (N=13) or no exercise (N=12) to compare the effects of these modes of training on anthropometric measures of fat distribution in previously sedentary males on an Ad Libitum diet. The ET significantly (P0.05). Plasma GH, cortisol and lactate increased significantly after exercise both bouts (P<0.01), but there were no significant changes between MS and P (P>0.05). CONCLUSION: It is concluded that the acute bout of resistance exercise following MS and P systems provide similar training strain when the total volume of load lifted is matched. PMID- 20585304 TI - Short duration exhaustive running exercise does not modify lipid hydroperoxide, glutathione peroxidase and catalase. AB - AIM: Oxidative stress occurs only when exercise is exhaustive and is independent of the absolute duration of exercise. In this study the effects of short duration (03:50 +/- 00:06 min) high-intensity exhaustive exercise on lipid peroxidation and antioxidant status were examined. METHODS: A total of thirty-seven male university students (23.9+/-0.6 years old) participated in this study. None was involved in a regular training program before the study. Intensities of exercises were determined according to the maximum slope and speed they could run in Bruce Test Protocol which is used for determining V.O2max of the participants. Just before and after the high intensity exhaustive running exercise test, venous blood was collected and centrifuged to separate the plasma. RESULTS: Lipid hydroperoxides (LOOH) did not change, glutathione peroxidase (GPx) decreased (2%) and catalase (CAT) increased (13%) at the pre and post exhaustive exercise test. These changes were not statistically significant (P>0.05). On the other hand, lactate dehydrogenase (LDH) levels significantly increased (31%) (P< 0.001). CONCLUSION: As a result, it may be claimed that short duration exhaustive exercise test produced no important changes in LOOH, GPx and CAT levels. And exhaustive exercise-induced oxidative stress may be related with exercise duration. PMID- 20585307 TI - Ex vivo changes in blood glucose levels seldom change blood glucose control algorithm recommendations. AB - BACKGROUND: Hyperglycemia and glycemic variabilities are associated with adverse outcomes in critically ill patients. Blood glucose control with insulin mandates an adequate and precise assessment of blood glucose levels. Blood glucose levels, however, can change ex vivo after sampling. The aim of this study was to determine whether this phenomenon affects the practice of blood glucose control. METHODS: We performed an observational study in a mixed medical-surgical intensive care unit (ICU). ICU nurses were the primary healthcare workers involved in the practice of blood glucose control, and they used an insulin titration method and blood-sampling algorithm aimed at maintaining blood glucose levels between 5 to 8 mmol/L. RESULTS: Blood glucose levels were measured directly after sampling, as well as after 30 and 60 minutes using the same samples. Blood glucose control algorithm recommendations were scored for each measurement. We collected 450 blood samples from 74 patients (median of 3 [2-8] samples per patient). The mean ex vivo changes in the blood glucose level were rather small (-0.1+/-1.6 mmol/L (range -1.4 to 0.7) and -0.2+/-1.6 mmol/L (range 1.3 to 0.5) at 30 and 60 minutes after sampling, respectively; P<0.05). An ex vivo change in the blood glucose level hardly ever resulted in a change in algorithm recommendation (4% and 6% at 30 and 60 minutes after sampling, respectively). In most cases the algorithm advised a lower insulin infusion speed. CONCLUSION: Ex vivo changes in blood glucose levels, although statistically significant, seem clinically irrelevant. PMID- 20585311 TI - Exploring dopaminergic activity in ring chromosome 20 syndrome: a SPECT study. AB - AIM: Several lines of evidence indicate that the dopaminergic system may play a role in the propagation of epileptic seizures and, indeed, DOPA metabolism impairment has recently been demonstrated in PET studies of ring chromosome 20 [r(20)] patients. We conducted a study looking for correlations between r(20) mosaicism, other clinical variables and both pre-synaptic dopamine transporter (DAT) expression and post-synaptic D2 receptor density. METHODS: Five patients with r(20) and epilepsy were enrolled in the study. DAT expression and D2 density were measured by single photon emission tomography (SPECT) imaging with 185 MBq of [123I]ioflupane and [123I]IBZM, respectively, on different days. Linear correlations between r(20) mosaicism, clinical variables and binding of [123I]ioflupane or [123I]IBZM were examined. RESULTS: A significant correlation between seizure frequency and r(20) mosaicism was detected (r=0.903, P<0.05), along with a negative correlation between r(20) mosaicism and binding of [123I]ioflupane in the putamen and in the caudate nucleus (r=-0.692 and r=-807; P<0.05). Seizure frequency was positively correlated with post-synaptic D2 density (r=0.925, P<0.05). CONCLUSION: Striatal neurons are involved in r(20) epilepsy; the relationship found between r(20) mosaicism and DAT expression suggests that drugs acting on the dopaminergic system could have a place in the treatment of this rare form of epilepsy. PMID- 20585312 TI - Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice. AB - The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known; however, its role in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav-1 KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan (Telm), and cardiac function was assessed by echocardiography. Treatment of Cav-1 KO mice with Telm significantly improved cardiac function compared with age matched vehicle-treated Cav-1 KO mice, whereas Telm did not affect cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by Telm in Cav-1 KO but not in WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides A and B, beta-myosin heavy chain and TGF-beta, and Telm treatment normalized the expression of these genes. Telm reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, Telm treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy. PMID- 20585315 TI - Transplantation: Pediatric kidney donation after cardiac death. AB - A Dutch study has evaluated the outcomes after transplantation of kidneys from pediatric patients after cardiac death. Such programs instigate ethical debate regarding the classification of donors, and raise questions about the suitability of protocols for determining when an individual can be declared dead, and thus, can donate their organs. PMID- 20585313 TI - ErbB4 promotes cyclooxygenase-2 expression and cell survival in colon epithelial cells. AB - The ErbB4 receptor tyrosine kinase is expressed at high levels in human and mouse colitis, and inhibits colon epithelial cell apoptosis in the presence of proinflammatory cytokines. In this study, we investigated the molecular mechanisms responsible for ErbB4-induced cell survival. In cultured mouse colon epithelial cells, ErbB4 overexpression resulted in increased levels of cyclooxygenase-2 (COX-2) mRNA and protein; in contrast, ErbB4 knockdown with siRNA blocked COX-2 accumulation in response to tumor necrosis factor. Although ErbB4 is expressed as up to four isoforms in epithelial tissues, its ability to promote COX-2 expression was isoform independent. ErbB4-stimulated COX-2 induction was associated with an increase in mRNA half-life and was blocked by inhibition of Src, phosphatidylinositol (PI) 3-kinase, or epidermal growth factor receptor (EGFR). Furthermore, ErbB4 expression promoted EGFR phosphorylation in the presence of heregulin, implicating ErbB4-EGFR heterodimerization in these responses. As to the cellular responses to ErbB4 activation, increased survival of ErbB4-expressing cells in the presence of proinflammatory cytokines was sensitive to the COX-2 inhibitor celecoxib. Furthermore, ErbB4-overexpressing cells acquired the ability to form colonies in soft agar, indicative of cellular transformation, also in a celecoxib-sensitive manner. Together our data indicate that ErbB4 is a key regulator of COX-2 expression and cellular survival in colon epithelial cells, acting in concert with EGFR through a Src- and PI 3-kinase dependent mechanism. These results suggest that chronic overexpression of ErbB4 in the context of inflammation could contribute to colitis-associated tumorigenesis by inhibiting colonocyte apoptosis. PMID- 20585316 TI - Dialysis: Can we predict death in patients on dialysis? AB - The survival advantages associated with renal replacement therapy might be counterbalanced by its negative effects on quality of life. Cohen et al. have proposed a simple mortality prediction model to help physicians discuss prognosis and individualized palliative care with patients on maintenance hemodialysis, to enable patients and their families make informed treatment decisions. PMID- 20585317 TI - Acute kidney injury: is acute kidney injury a risk factor for long-term mortality? AB - Acute kidney injury seems to have sequelae long beyond the index hospitalization. A new study suggests that even after adjusting for the impact of subsequent chronic kidney disease, acute kidney injury is associated with an increased risk of death. PMID- 20585318 TI - End-stage renal disease: a new comorbidity index for estimating mortality risk in ESRD. AB - A new comorbidity index predicts the risk of mortality in patients with end-stage renal disease (eSrD). This index, which was developed using data from a large US database, is an important tool for observational research in patients with eSrD, but its value in patient populations other than dialysis populations in the US needs to be validated. PMID- 20585319 TI - Pediatrics: Acute kidney injury leads to pediatric patient mortality. AB - Data are lacking on the impact of acute kidney injury (AKI) in children admitted to an intensive care unit. Schneider and colleagues have now performed a large scale assessment of the use of the rIFle criteria for characterizing AKI in children and have determined the mortality and morbidity associated with AKI in this patient group. PMID- 20585320 TI - What should patients be told about obesity-related risks? PMID- 20585321 TI - Choroidal ruptures after adjuvant intravitreal injection of bevacizumab for aggressive posterior retinopathy of prematurity. AB - In recent times, laser treatment combined with intravitreal bevacizumab (Avastin) has been used rarely as early investigations to treat patients with aggressive posterior retinopathy of prematurity (ROP). We describe choroidal ruptures that were documented at 10 weeks after this combined treatment in a preterm infant born at 28 weeks gestation with a birth weight of 1190 g. Aggressive posterior ROP was diagnosed at the age of 6 weeks. Initial treatment included bilateral laser ablation, followed immediately by intravitreal bevacizumab (IVB, 0.75 mg) in the right eye. On day 5, a remarkable regression of plus sign and fibrovascular proliferation was noted only in the right eye. At this point, additional laser treatment combined with IVB was given in the left eye, which dramatically resolved plus disease and neovascularization. At 10 weeks after IVB in the left eye, two sites of choroidal ruptures were revealed along the posterior edges of laser scars. There was no evidence of choroidal neovascularization associated with the choroidal ruptures. Choroidal rupture may occur shortly after laser ablation plus IVB treatment for aggressive posterior ROP. This occurrence requires recognition to determine whether it is actually related to the treatment. Long-term follow-up is important for understanding the nature and progression of this potentially serious complication. PMID- 20585322 TI - Intermittent 'bulge' in the umbilical cord. PMID- 20585324 TI - Genome-wide association study of conduct disorder symptomatology. AB - Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 * 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder. PMID- 20585325 TI - Impaired glycolytic response in peripheral blood mononuclear cells of first-onset antipsychotic-naive schizophrenia patients. AB - Little is known about the biological mechanisms underpinning the pathology of schizophrenia. We have analysed the proteome of stimulated and unstimulated peripheral blood mononuclear cells (PBMCs) from schizophrenia patients and controls as a potential model of altered cellular signaling using liquid chromatography mass spectrometry proteomic profiling. PBMCs from patients and controls were stimulated for 72 h in vitro using staphylococcal enterotoxin B. In total, 18 differentially expressed proteins between first-onset, antipsychotic naive patients and controls in the unstimulated and stimulated conditions were identified. Remarkably, eight of these proteins were associated with the glycolytic pathway and patient-control differences were more prominent in stimulated compared with unstimulated PBMCs. None of these proteins were altered in chronically ill antipsychotic-treated patients. Non-linear multivariate statistical analysis showed that small subsets of these proteins could be used as a signal for distinguishing first-onset patients from controls with high precision. Functional analysis of PBMCs did not reveal any difference in the glycolytic rate between patients and controls despite increased levels of lactate and the glucose transporter-1, and decreased levels of the insulin receptor in patients. In addition, subjects showed increased serum levels of insulin, consistent with the idea that some schizophrenia patients are insulin resistant. These results show that schizophrenia patients respond differently to PBMC activation and this is manifested at disease onset and may be modulated by antipsychotic treatment. The glycolytic protein signature associated with this effect could therefore be of diagnostic and prognostic value. Moreover, these results highlight the importance of using cells for functional discovery and show that it may not be sufficient to measure protein expression levels in static states. PMID- 20585326 TI - Long-lasting involuntary motor activity after spinal cord injury. AB - STUDY DESIGN: The study design used is prospective cohort study. OBJECTIVES: This study was designed to neurophysiologically characterize spinal motor activity during recovery from spinal cord injury (SCI). SETTING: University of Louisville, Louisville, Kentucky, USA. METHODS: Twenty-five consecutive acute SCI admissions were recruited for this study. The American Spinal Injury Association Impairment Scale (AIS) was used to categorize injury level and severity at onset. Surface EMG recording was carried out initially between the day of admission and 17 days post-onset (6.0 +/- 4.3, mean +/- s.d. days). Follow-up recordings were performed for up to 9 months after injury. Initial AIS distribution was 7 AIS-A; 3 AIS-B; 2 AIS-C; 13 AIS-D. RESULTS: Twelve subjects (48%) showed long-duration involuntary motor-unit activation during relaxation. This activity was seen on initial examination in nine and on follow-up by 3 months post-injury in three others. It was seen in muscles innervated from the injury zone in 11 and caudal to the lesion in 9 subjects. This activity was independent of the presence or absence of tendon reflexes and the ability to volitionally suppress plantar stimulation elicited reflex withdrawal. CONCLUSION: The form of involuntary activity described here is the likely result of the altered balance of excitation and inhibition reaching spinal motor neurons because of the loss of inhibitory interneurons or their reduced activation by damaged supraspinal drive and the synaptic reorganization that follows SCI. As such, this activity may be useful for monitoring the effects of neuroprotective and restorative intervention strategies in persons with SCI. PMID- 20585327 TI - Diagnostic criteria of traumatic central cord syndrome. Part 2: a questionnaire survey among spine specialists. AB - STUDY DESIGN: A questionnaire survey. OBJECTIVES: To evaluate the need for the introduction of quantitative diagnostic criteria for the traumatic central cord syndrome (TCCS). SETTING: An online questionnaire survey with participants from all over the world. METHODS: An invitation to participate in an eight-item online survey questionnaire was sent to surgeon members of AOSpine International. RESULTS: Out of 3340 invited professionals, 157 surgeons (5%) from 41 countries completed the survey. Whereas most of the respondents (75%) described greater impairment of the upper extremities than of the lower extremities in their own TCCS definitions, symptoms such as sensory deficit (39%) and bladder dysfunctions (24%) were reported less frequently. Initially, any difference in motor strength between the upper and lower extremities was considered most frequently (23%) as a 'disproportionate' difference in power. However, after presenting literature review findings, the majority of surgeons (61%) considered a proposed difference of at least 10 points of power (based on the Medical Research Council scale) in favor of the lower extremities as an acceptable cutoff criterion for a diagnosis of TCCS. Most of the participants (40%) felt that applying a single criterion to the diagnosis of TCCS is insufficient for research purposes. CONCLUSION: Various definitions of TCCS were used by physicians involved in the spinal trauma care. The authors consider a difference of at least 10 motor score points between upper and lower extremity power a clear diagnostic criterion. For clinical research purposes, this diagnostic criterion can be considered as a face valid addendum to the commonly applied TCCS definition as introduced by Schneider et al. PMID- 20585328 TI - Effects of iloprost and piracetam in spinal cord ischemia-reperfusion injury in the rabbit. AB - STUDY DESIGN: Experimental Study. OBJECTIVES: The aim of this study was to investigate the neuroprotective effects of iloprost and piracetam on spinal cord ischemia/reperfusion (I/R) injury in the rabbit. SETTINGS: The Experimental Research Center of Selcuk University, Konya, Turkey. METHODS: A total of 24 rabbits were divided into four groups of six rabbits each, as follows: group 1 (n = 6) sham, laparotomy only; group 2 (n = 6) I/R; group 3 (n = 6) I/R+iloprost; and group 4 (n = 6) I/R+piracetam. I/R was established in groups 2, 3 and 4. Subsequently, they were followed up neurologically for 24 h until the rabbits were killed; biochemical and histopathological examinations of samples from the spinal cord were carried out. RESULTS: Neurological examination results were significantly better in the iloprost and piracetam groups compared with the I/R group (P < 0.05). Neuroprotection was achieved with iloprost and piracetam by suppressing malondialdehyde (P < 0.05), increasing glutathione peroxidase activity (P < 0.05) and decreasing the xanthine oxidase level. In histopathological assessment, iloprost and piracetam groups were statistically different from the I/R group in terms of the number of apoptotic neurons in gray matter and white matter, as well as in terms of degenerated neurons and glial cells (P < 0.05). No statistical difference was determined between the four groups in the number of degenerated glial cells (P > 0.05). CONCLUSION: This study has shown that iloprost and piracetam have neuroprotective effects in I/R injury both neurologically and histopathologically because of inhibition of lipid peroxidation. PMID- 20585329 TI - Four decades of Fontan palliation. AB - The Fontan palliation was introduced in 1968 to treat cardiac malformations unsuitable for biventricular repair. This procedure has transformed the surgical management of congenital heart disease. In this Review, we reflect on the outcomes and clinical problems associated with this unique circulation after more than 40 years of experience. We also summarize the evolution of the Fontan procedure, highlight the long-term clinical issues and their management, and consider future expectations of a circulation driven by a single ventricle with the systemic and pulmonary blood flow in series rather than in parallel. PMID- 20585330 TI - New antithrombotic agents--insights from clinical trials. AB - Antithrombotic agents are the cornerstones of therapy for thrombosis. The compositions of arterial and venous clots differ, rendering antiplatelet agents more effective for arterial thrombosis and anticoagulants more effective for venous disease. Despite taking acetylsalicylic acid, some patients with arterial disease experience thrombotic events. The addition of the ADP-receptor antagonist clopidogrel to therapeutic regimens containing acetylsalicylic acid improves outcomes in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. However, clopidogrel has several limitations, including variable absorption, drug-drug interactions and genetic factors that lead to reduced generation of the active metabolite, and a delayed onset and offset of action. A search for new ADP-receptor inhibitors has yielded drugs such as prasugrel, ticagrelor, and cangrelor. For patients with venous thrombosis, the coumarins have been the only available oral anticoagulants for more than 60 years. Despite their effectiveness in preventing and treating thromboembolism, coumarins have well-documented limitations, including drug-drug and drug-dietary interactions, a narrow therapeutic range, and inconvenience and cost of monitoring therapy. A search for new oral anticoagulants has yielded drugs such as dabigatran etexilate, rivaroxaban, and apixaban. In this article, we review these new antithrombotic agents and provide plausible explanations for the results of phase III randomized controlled trials of these drugs. PMID- 20585332 TI - X inactivation: Get in LINE for silencing. PMID- 20585333 TI - Development: A code to distinguish winners and losers. PMID- 20585331 TI - Plant immunity: towards an integrated view of plant-pathogen interactions. AB - Plants are engaged in a continuous co-evolutionary struggle for dominance with their pathogens. The outcomes of these interactions are of particular importance to human activities, as they can have dramatic effects on agricultural systems. The recent convergence of molecular studies of plant immunity and pathogen infection strategies is revealing an integrated picture of the plant-pathogen interaction from the perspective of both organisms. Plants have an amazing capacity to recognize pathogens through strategies involving both conserved and variable pathogen elicitors, and pathogens manipulate the defence response through secretion of virulence effector molecules. These insights suggest novel biotechnological approaches to crop protection. PMID- 20585334 TI - Defect in efferocytosis leads to alternative activation of macrophages in Francisella infections. AB - The macrophage is a versatile cell type that can sense and respond to a particular need based on the conditions of the microenvironment. Some studies have recently suggested that pathogens can directly influence the polarization of macrophages. As Francisella infections are characterized by intense necrotic infiltrates in the lung as well as in distal sites of infection, we sought to investigate whether pulmonary Francisella infections could cause the polarization of alternatively activated macrophages (M2/aaMs). Our results indicate that Francisella infections can cause the polarization of M2/aaM in vivo and that macrophages can be polarized toward an M2/aaM phenotype more potently if dead cell debris is used for stimulation in the presence and absence of Francisella infections. Finally, we also demonstrate that efferocytosis is inhibited in macrophages infected with Francisella, thus providing a potential explanation for the lack of clearance and eventual accumulation of dead cell debris associated with this disease. PMID- 20585335 TI - Polyclonal Treg cells enhance the activity of a mucosal adjuvant. AB - The efficacy of vaccines can be greatly improved by adjuvants that enhance and modify the magnitude and the duration of the immune response. Several approaches to design rational adjuvants are based on the suppression of regulatory T-cell (Treg) function. Here, we evaluated whether removal or addition of Treg at the time of vaccination with tetanus toxoid and the mucosal adjuvant cholera toxin (CT), would affect immune responses. We found that depletion/inactivation of CD4(+)CD25(+) Treg, either by treatment of BALB/c mice with anti-CD25 monoclonal antibodies or by adoptive transfer of CD4(+)CD25(-) T lymphocytes depleted of CD4(+)CD25(+) Treg into nu/nu mice, impaired antibody production after mucosal immunization in the presence of CT. Conversely, transfer of polyclonal, but not Ag-specific, CD4(+)CD25(+)Foxp3(+) Treg to normal BALB/c mice enhanced CT-induced antibody responses. An increased titer of both immunoglobulin IgG1 and IgG2a antibody subclasses was found, however, the ratio between IgG1/IgG2a with or without polyclonal Treg was comparable, suggesting that polyclonal Treg influence the magnitude, but not the quality of the immune response. Recipients of polyclonal Treg that had been immunized with CT had an increased number of Ag specific CD4(+) T cells with an activated phenotype (CD44(hi)) in the draining lymph nodes. This accumulation of Ag-specific CD4(+) T lymphocytes could favour the germinal centre formation and may promote T-dependent B-cell responses. Overall, our study indicates that Foxp3(+) Treg can not only function as suppressor cells but also as helper T cells, depending on the type of immune response being evaluated and the microenvironment in which the response is generated. PMID- 20585336 TI - Innate lymphocytes induce inflammatory bowel disease. PMID- 20585337 TI - Lowering TCR expression on naive CD8+ T cells does not affect memory T-cell differentiation. AB - The generation of long-lived memory T (Tm) cells is critical for the success of vaccination, but the factors controlling their differentiation are still poorly defined. We examined the hypothesis that the level of T-cell receptor (TCR) engagement contributed to memory CD8(+) T-cell generation. By manipulating TCR expression levels on murine, naive ovalbumin (OVA)-specific CD8(+) T cells, we showed that the expansion of antigen (Ag)-specific CD8(+) T cells is minimally affected by the level of TCR expression. Indeed, naive CD8(+) T cells expressing as little as a 1000 TCRs (30-fold less) show only a 2.5-fold reduction in the number of effectors generated. Furthermore, the TCR expression levels influenced neither the acquisition of effector functions nor the generation of functional Tm cells. Our data indicate that during an in vivo immune response, a threshold in the number of TCRs engaged by naive CD8(+) T cells is required for full T-cell expansion but not for their differentiation into effector and Tm cells. PMID- 20585338 TI - IBS: An epigenetic perspective. AB - IBS is a common and debilitating disorder. The pathophysiology of IBS is poorly understood and is currently viewed as a biopsychosocial disorder with symptoms mediated via the brain-gut axis. Epidemiological studies of IBS point to risk factors such as familial clustering, sexual abuse and other forms of childhood trauma, low birth weight and gastrointestinal infection. Epigenetics focuses on the complex and dynamic interaction between the DNA sequence, DNA modifications and environmental factors, all of which combine to produce the phenotype. Studies in animal models of early stress and in humans who have experienced childhood trauma or abuse suggest that these events can lead to long-lasting epigenetic changes in the glucocorticoid receptor gene brought about by hypermethylation of a key regulatory component. Animal studies also indicate that the microbiota has a pivotal role in programming the core stress system, the hypothalamic-pituitary adrenal axis and the immune system through epigenetic mechanisms. In this Perspectives, an epigenetic model of IBS is presented that incorporates many of the current findings regarding IBS, including proinflammatory markers, neuroendocrine alterations and links with both psychosocial stress and stress related to infection. We conclude that applying epigenetic methodology to this common and disabling disorder may help unravel its complex pathophysiology and lead to more effective treatments. PMID- 20585339 TI - Evolving challenges in hepatic fibrosis. AB - Continued elucidation of the mechanisms of hepatic fibrosis has yielded a comprehensive and nuanced portrait of fibrosis progression and regression. The paradigm of hepatic stellate cell (HSC) activation remains the foundation for defining events in hepatic fibrosis and has been complemented by progress in a number of new areas. Cellular sources of extracellular matrix beyond HSCs have been identified. In addition, the role of chemokine, adipokine, neuroendocrine, angiogenic and NAPDH oxidase signaling in the pathogenesis of hepatic fibrosis has been uncovered, as has the contribution of extracellular matrix stiffness to fibrogenesis. There is also increased awareness of the contribution of innate immunity and greater understanding of the complexity of gene regulation in HSCs and myofibroblasts. Finally, both apoptosis and senescence have been recognized as orchestrated programs that eliminate fibrogenic cells during resolution of liver fibrosis. Ironically, the progress that has been made has highlighted the growing disparity between advances in the experimental setting and their translation into new diagnostic tools and treatments. As a result, focus is shifting towards overcoming key translational challenges in order to accelerate the development of new therapies for patients with chronic liver disease. PMID- 20585341 TI - Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. AB - MicroRNAs are non-coding RNAs that can block mRNA translation and influence mRNA stability. Recent evidence indicates that miRNA variations can affect drug resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics research. We investigated associations between polymorphisms in both miRNA containing genomic regions (primary and precursor miRNA) and in genes related to miRNA biogenesis with clinical outcome in metastatic colorectal cancer (mCRC) patients treated with 5-fluorouracil and irinotecan (CPT-11). Eighteen single nucleotide polymorphisms (SNPs) were analyzed in 61 patients. A significant association with tumor response and time to progression (TTP) was found for SNP rs7372209 in pri-miR26a-1 (P=0.041 and P=0.017, respectively). The genotypes CC and CT were favorable when compared with the TT variant genotype. In addition, SNP rs1834306, located in the pri-miR-100 gene, significantly correlated with a longer TTP (P=0.04). In the miRNA-biogenesis pathway, a trend was identified between SNP rs11077 in the exportin-5 gene and disease control rate (P=0.076). This study is the first to suggest a relationship between treatment outcome and SNPs in the miRNA-biogenesis machinery, in both primary and precursor miRNAs. Our results suggest that miRNA polymorphic variants might be useful predictors of clinical outcome in mCRC patients treated with 5-fluorouracil and CPT-11 combination. PMID- 20585340 TI - Cellular and molecular aspects of vascular dysfunction in systemic sclerosis. AB - Systemic sclerosis (SSc) is characterized by vascular alterations, activation of the immune system and tissue fibrosis. Vascular insufficiency manifests early in the disease, and although there is evidence of an active repair process, capillaries deteriorate and regress. Factors that contribute to the failure of vascular regeneration might include persistent injury, an imbalance between proangiogenic and antiangiogenic mediators, intrinsic abnormal properties of the cellular components of the vessels, and the presence of fibroblast-derived antiangiogenic factors. In addition, circulating dysfunctional endothelial progenitor cells might further exacerbate vessel deterioration. Abnormal expression of transcription factors, including Fra2 and Fli1, has been proposed to contribute to SSc vasculopathy. Fli1 regulates genes that are involved in vessel maturation and stabilization, suggesting that reduced levels of Fli1 in SSc vasculature could contribute to the development of unstable vessels that are prone to regression. Conversely, proliferating endothelial cells and pericytes, in the presence of an appropriate stimulus, might transdifferentiate into collagen-producing cells, and thus contribute to the initiation of fibrosis. Despite progress in treating the symptoms of vascular disease in SSc, the underlying mechanisms remain poorly understood. An improved knowledge of the molecular and cellular pathways that contribute to SSc vasculopathy could help in the design of effective therapies in the future. PMID- 20585342 TI - Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate. AB - In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate. PMID- 20585343 TI - The function of microRNAs, small but potent molecules, in human prostate cancer. AB - Prostate cancer is one of the most significant cancers of men all over the world. The microRNAs (miRNAs) possess crucial functions in pathogenesis of the disease and its gain of androgen independency. The miRNAs are small, approximately 18-24 nucleotides, non-coding, endogenously synthesized RNAs that regulate gene expression post-transcriptionally. They are found in viruses, plants, and animal cells. The miRNAs have critical functions in gene expression and their dysregulation may cause tumor formation and progression of several diseases. Here, we have reviewed the most current literature to elucidate the function of miRNAs in human prostate cancer. We believe that this will help investigators not only working in prostate cancer, but also studying the miRNAs in other diseases to delineate the functions of miRNAs implicated in human prostate cancer development and progression. PMID- 20585345 TI - Heat-shock protein 70 expression in the seminal plasma of patients with chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome. AB - The purpose of this study was to assess the diagnostic value and potentially protective capacity of heat-shock protein 70 (HSP70) in chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this study, seminal plasma levels of cytokines (tumor necrosis factor-alpha (TNF alpha) and interleukin 1beta (IL-1beta)) and HSP70 were evaluated by enzyme linked immunosorbent assay in 80 men: 15 healthy controls, 16 men with chronic bacterial prostatitis, 23 men with CP/CPPS IIIA and 26 with CP/CPPS IIIB. The HSP70 levels in chronic bacterial prostatitis and CP/CPPS patients were correlated with chronic prostatitis symptom index (CPSI). Significantly increased levels of cytokines (TNF-alpha and IL-1beta) and HSP70 were observed in seminal plasmas from patients with chronic bacterial prostatitis compared with CP/CPPS patients and controls. However, only IL-1beta was significantly elevated compared with CP/CPPS IIIB and controls in patients with CP/CPPS IIIA. HSP70 levels in CP/CPPS patients were significantly lower than that in controls. HSP70 concentration in seminal plasma was negatively correlated with CPSI in chronic bacterial prostatitis. The results indicated that HSP70 and IL-1beta appear to be the most reliable and predictive surrogate markers to diagnose chronic bacterial prostatitis and CP/CPPS, respectively. HSP70 has an important protective role in the regulation of cell functions in chronic bacterial prostatitis. CP/CPPS would probably be detrimental to the ability of T cells and consequently suppress the expression of HSP70. PMID- 20585344 TI - ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification. AB - Gene fusions prevalent in prostate cancer (CaP) lead to the elevated expression of the ERG proto-oncogene. ERG activation present in 50-70% of prostate tumors underscores one of the most common oncogenic alterations in CaP. Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein status in CaP still remains to be defined. Furthermore, development of ERG protein-based assays may provide a new dimension to evaluation of gene fusions involving diverse androgen regulated promoters and the ERG protein-coding sequence. Through exhaustive evaluations of 132 whole-mount prostates (261 tumor foci and over 200 000 benign glands) for the ERG oncoprotein nuclear expression, we demonstrated 99.9% specificity for detecting prostate tumor cells using a highly specific anti-ERG monoclonal antibody. The ERG oncoprotein expression correlated well with fusion transcript or gene fusion in randomly selected specimens. Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients. Conversely, ERG negative PINs were associated with ERG-negative carcinoma. Taken together, the homogeneous and strong ERG expression detected in individual tumors establishes the potential for ERG oncoprotein-based stratification of CaP. PMID- 20585346 TI - Bowels control brain: gut hormones and obesity. AB - Food intake and energy expenditure are tightly regulated by the brain, in a homeostatic process that integrates diverse hormonal, neuronal and metabolic signals. The gastrointestinal tract is an important source of such signals, which include several hormones released by specialized enteroendocrine cells. These hormones exert powerful effects on appetite and energy expenditure. This Review addresses the physiological roles of peptide YY, pancreatic polypeptide, islet amyloid polypeptide, glucagon-like peptide 1, glucagon, oxyntomodulin, cholecystokinin and ghrelin and discusses their potential as targets for the development of novel treatments for obesity. PMID- 20585348 TI - Lymphocytic hypophysitis with diabetes insipidus in a young man. AB - BACKGROUND: A 29-year-old man was referred to a multidisciplinary pituitary clinic with a 3.5-year history of central diabetes insipidus, initially presumed to be idiopathic based on a normal MRI scan of the pituitary gland. Subsequent scanning revealed a suprasellar mass, which demonstrated progressive enlargement on serial imaging. He also developed hypogonadotropic hypogonadism. INVESTIGATIONS: Measurement of levels of serum morning fasting cortisol, adrenocorticotropic hormone, total testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, insulin-like growth factor 1, TSH and free T(4), MRI of the pituitary gland and a transsphenoidal biopsy of a pituitary mass were performed. DIAGNOSIS: Lymphocytic hypophysitis presenting with diabetes insipidus, with development of hypogonadotropic hypogonadism and a suprasellar mass. MANAGEMENT: The patient was treated with intranasal desmopressin and transdermal testosterone. The underlying lymphocytic hypophysitis was initially managed conservatively with serial MRI and visual field testing. No immunosuppressant medication was given and, aside from the diagnostic transsphenoidal biopsy, no surgical intervention was required. He subsequently developed secondary hypothyroidism, secondary adrenal insufficiency and growth hormone deficiency. These disorders were managed with levothyroxine and prednisone. PMID- 20585347 TI - Cardiovascular involvement in patients with different causes of hyperthyroidism. AB - Various clinical disorders can cause hyperthyroidism, the effects of which vary according to the patient's age, severity of clinical presentation and association with other comorbidities. Hyperthyroidism is associated with increased morbidity and mortality from cardiovascular disease, although whether the risk of specific cardiovascular complications is related to the etiology of hyperthyroidism is unknown. This article will focus on patients with Graves disease, toxic adenoma and toxic multinodular goiter, and will compare the cardiovascular risks associated with these diseases. Patients with toxic multinodular goiter have a higher cardiovascular risk than do patients with Graves disease, although cardiovascular complications in both groups are differentially influenced by the patient's age and the cause of hyperthyroidism. Atrial fibrillation, atrial enlargement and congestive heart failure are important cardiac complications of hyperthyroidism and are prevalent in patients aged > or = 60 years with toxic multinodular goiter, particularly in those with underlying cardiac disease. An increased risk of stroke is common in patients > 65 years of age with atrial fibrillation. Graves disease is linked with autoimmune complications, such as cardiac valve involvement, pulmonary arterial hypertension and specific cardiomyopathy. Consequently, the etiology of hyperthyroidism must be established to enable correct treatment of the disease and the cardiovascular complications. PMID- 20585349 TI - Genetic and cellular characterization of Caenorhabditis elegans mutants abnormal in the regulation of many phase II enzymes. AB - BACKGROUND: The phase II detoxification enzymes execute a major protective role against xenobiotics as well as endogenous toxicants. To understand how xenobiotics regulate phase II enzyme expression, acrylamide was selected as a model xenobiotic chemical, as it induces a large number and a variety of phase II enzymes, including numerous glutathione S-transferases (GSTs) in Caenorhabditis elegans. METHODOLOGY/PRINCIPAL FINDINGS: To begin dissecting genetically xenobiotics response pathways (xrep), 24 independent mutants of C. elegans that exhibited abnormal GST expression or regulation against acrylamide were isolated by screening about 3.5x10(5) genomes of gst::gfp transgenic strains mutagenized with ethyl methanesulfonate (EMS). Complementation testing assigned the mutants to four different genes, named xrep-1, -2, -3, and -4. One of the genes, xrep-1, encodes WDR-23, a nematode homologue of WD repeat-containing protein WDR23. Loss of-function mutations in xrep-1 mutants resulted in constitutive expression of many GSTs and other phase II enzymes in the absence of acrylamide, and the wild type xrep-1 allele carried on a DNA construct successfully cured the mutant phenotype of the constitutive enzyme expression. CONCLUSIONS/SIGNIFICANCE: Genetic and cellular characterization of xrep-1 mutants suggest that a large number of GSTs and other phase II enzymes induced by acrylamide are under negative regulation by XREP-1 (WDR-23), which is likely to be a functional equivalent of mammalian Keap1 and a regulator of SKN-1, a C. elegans analogue of cap-n-collar Nrf2 (nuclear factor erythroid 2-related factor 2). PMID- 20585350 TI - What the CERAD Battery Can Tell Us about Executive Function as a Higher-Order Cognitive Faculty. AB - Executive function (EF) is believed to control or influence the integration and application of cognitive functions such as attention and memory and is an important area of research in cognitive aging. Recent studies and reviews have concluded that there is no single test for EF. Results from first-order latent variable modeling have suggested that little, if any, variability in cognitive performance can be directly (and uniquely) attributed to EF; so instead, we modeled EF, as it is conceptualized, as a higher-order function, using elements of the CERAD neuropsychological battery. Responses to subtests from two large, independent cohorts of nondemented elderly persons were modeled with three theoretically plausible structural models using confirmatory factor analysis. Robust fit statistics, generated for the two cohorts separately, were consistent and support the conceptualization of EF as a higher-order cognitive faculty. Although not specifically designed to assess EF, subtests of the CERAD battery provide theoretically and empirically robust evidence about the nature of EF in elderly adults. PMID- 20585351 TI - Identifying and improving knowledge deficits of emergency airway management of tracheotomy and laryngectomy patients: a pilot patient safety initiative. AB - Objectives. To evaluate the knowledge base of hospital staff regarding emergent airway management of tracheotomy and laryngectomy patients, and the impact of the introduction of a bedside airway form. Methods. Cross-sectional surveys of physicians, nurses, and respiratory therapists at a tertiary care hospital prior to and 24 months after introduction of a bedside Emergency Airway Access (EAA) form. Results. Pre- and postintervention surveys revealed several knowledge deficits. Preintervention, 37% of medical internists and 19% overall did not know that laryngectomy patients cannot be orally ventilated, and 67% of internists could not identify the purpose of stay sutures in recently created tracheotomies. Postintervention, these numbers improved for all groups. Furthermore, 80% of respiratory therapists reported encountering the EAA form in an emergent situation and found it useful. Conclusion. A knowledge deficit is identified in caregivers expected to provide emergency management of patients with airway anatomy altered by subspecialty surgeons. Safety initiatives such as the EAA form may improve knowledge among providers. PMID- 20585352 TI - Clinical Use of Cinacalcet in MEN1 Hyperparathyroidism. AB - Background. Management of multiple-endocrine neoplasia type 1- (MEN1-) associated hyperparathyroidism is associated with high recurrence rates and high surgical morbidity due to multiple neck explorations. Cinacalcet, a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism and parathyroid carcinoma, may provide a medical alternative for the management of these complex patients. Methods. A prospective audit was performed of eight patients; three males and five females, aged 20-38 at diagnosis. Two patients commenced cinacalcet as primary treatment and six had previous surgery. Six patients had complications of hyperparathyroidism: renal calculi, renal dysfunction, and reduced bone mineral density. All were commenced on cinacalcet 30 mg bd for MEN1 associated hyperparathyroidism; doses were subsequently reduced to 30 mg od in four patients. Results. Significant reductions were observed in serum calcium and PTH measurements. Serum calcium reduced by a median of 0.35 mmol/L (P = .012 Wilcoxon Signed Rank). Serum PTH levels decreased by a median of 5.05 pmol/L (P = .012). There was no change in urine calcium. Duration ranged from 10-35 months with maintenance of control. Cinacalcet was well tolerated by six patients; one experienced nausea and one experienced diarrhoea. Conclusion. Cinacalcet is an effective and well-tolerated medical treatment for the management of complex primary hyperparathyroidism. PMID- 20585353 TI - A topological description of hubs in amino Acid interaction networks. AB - We represent proteins by amino acid interaction networks. This is a graph whose vertices are the proteins amino acids and whose edges are the interactions between them. Once we have compared this type of graphs to the general model of scale-free networks, we analyze the existence of nodes which highly interact, the hubs. We describe these nodes taking into account their position in the primary structure to study their apparition frequency in the folded proteins. Finally, we observe that their interaction level is a consequence of the general rules which govern the folding process. PMID- 20585354 TI - Age-Related Differences in Stepping Response When Stepping onto a Known Soft Surface under Dual Task Conditions. AB - The purpose of this study was to investigate whether age-related differences in stepping response influence postural control when stepping onto a known soft surface under dual task conditions. Nine young and eleven older female adults participated. First, they stepped on a flat surface while grasping an empty cup (single task), and then they repeated the task while grasping a cup filled with water (dual task). For the second experiment, they stepped on a soft surface placed in front of them while performing the above tasks. The main result was that %DIP (initiation phase as a percentage of the total stepping task time) was significantly higher for older than for young adults during the dual task on the soft surface. In conclusion, caution due to previous experience may increase attentional demand during dual tasks and lengthen the time required for central nervous processing in order to avoid losing postural stability in older adults, resulting in reductions in step velocity and step length compared to those in young adults. PMID- 20585355 TI - Identification of residues important for the activity of Haloferax volcanii AglD, a component of the archaeal N-glycosylation pathway. AB - In Haloferax volcanii, AglD adds the final hexose to the N-linked pentasaccharide decorating the S-layer glycoprotein. Not knowing the natural substrate of the glycosyltransferase, together with the challenge of designing assays compatible with hypersalinity, has frustrated efforts at biochemical characterization of AglD activity. To circumvent these obstacles, an in vivo assay designed to identify amino acid residues important for AglD activity is described. In the assay, restoration of AglD function in an Hfx. volcanii aglD deletion strain transformed to express plasmid-encoded versions of AglD, generated through site directed mutagenesis at positions encoding residues conserved in archaeal homologues of AglD, is reflected in the behavior of a readily detectable reporter of N-glycosylation. As such Asp110 and Asp112 were designated as elements of the DXD motif of AglD, a motif that interacts with metal cations associated with nucleotide-activated sugar donors, while Asp201 was predicted to be the catalytic base of the enzyme. PMID- 20585356 TI - Dietary intake and physical activity of normal weight and overweight/obese adolescents. AB - Purpose. To evaluate the relationship between overweight/obesity and dietary/lifestyle factors among Italian adolescents. Methods. On a total of 756 adolescents with mean age 12.4 +/- 0.9, body mass index, food consumption, and time dedicated to after school physical activities and to TV viewing were determined. The data were analysed according to age, nutritional status, and gender. The analysis of variance and multiple logistic regression analysis were performed to investigate the association between dietary/lifestyle factors and overweight/obesity. Results. The percentages of overweight and obesity were, respectively, 28% and 9% among boys, 24% and 7% among girls. The overweight/obesity condition in both genders was associated with parental overweight/obesity (P < .001 for mother), less time devoted to physical activity (P < .001 for boys and P < .02 for girls) and being on a diet (P < .001). Direct associations were also observed between BMI and skipping breakfast and the lower number of meals a day (boys only). Conclusions. This pilot study reveals some important dietary and lifestyle behaviour trends among adolescents that assist with identification of specific preventive health actions. PMID- 20585357 TI - Endomyocardial biopsy of right atrial angiosarcoma guided by intracardiac echocardiography. AB - We report a case of a 22-year-old female who presented with pericardial effusion and cardiac tamponade. She was diagnosed with a right atrial mass by computed tomography and was referred to our institution for biopsy of this mass. Transcatheter biopsy was performed with intracardiac echocardiography (ICE) guidance, avoiding the need for transesophageal echocardiography or surgery to obtain the biopsy. ICE for transcatheter biopsy of an intracardiac mass is an attractive modality which provides precise localization of the cardiac structures. PMID- 20585359 TI - Synthesis and Characterization of a Linear [Mn(3)(O(2)CMe)(4)(py)(8)] Complex. AB - Two new compounds that consist of the linear trinuclear manganese(II) cation [Mn(3)(O(2)CMe)(4)(py)(8)](2+) cocrystallizing with different counteranions (I(3) (-), [1]; ClO(4) (-), [2]) are reported. Complex 1 was prepared from the reaction of [Mn(O(2)CMe)(2)] . 4H(2)O with I(2) in MeCO(2)H/py, whereas complex 2 was isolated from the reaction of [Mn(3)O(O(2)CMe)(6)(py)(3)] . py with [Mn(ClO(4))(2)] . 6H(2)O in MeCN/py. The crystal structures of both compounds were determined by single crystal X-ray crystallography. Magnetic susceptibility studies that were performed in microcrystalline powder of 1 in the 2-300 K range revealed the presence of antiferromagnetic exchange interactions that resulted in an S = 5/2 ground spin state. PMID- 20585358 TI - Mood disorders are glial disorders: evidence from in vivo studies. AB - It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment. PMID- 20585360 TI - Growth hormone deficiency in a case of crouzon syndrome with hydrocephalus. AB - Crouzon syndrome is one of the most common craniofacial syndromes and is inherited as autosomal dominant with variable expression. We report an 11 and a half-year-old boy with Crouzon syndrome with severe growth retardation. He had hydrocephalus since infancy and recently suffered from frequent dizziness. His bone age was only 5 years according to the Greulich and Pyle atlas. Magnetic resonance imaging showed shallow orbits, obstructive hydrocephalus, and cerebellar tonsil herniation. Growth hormone provocative tests revealed a reduced peak growth hormone response in both insulin and clonidine tests. Severe iron deficiency anemia was noted at the same time. Molecular analysis identified a common mutation point of Cys278Phe for Crouzon syndrome in exon IIIa of the fibroblast growth factor receptor 2 (FGFR2) gene. Since growth retardation is not a common feature of Crouzon syndrome, we reviewed the literature for the incidence of hydrocephalus in Crouzon syndrome and the association with growth hormone deficiency. PMID- 20585361 TI - Gallstone ileus of the sigmoid colon: an unusual cause of large-bowel obstruction. AB - Gallstone ileus of the colon is an exceedingly rare cause of large-bowel obstruction. It is usually the result of fistula formation between the gallbladder and large bowel facilitating entry of the stone into gastrointestinal tract. Contrast enhanced abdominal computed tomography is an important diagnostic aid. Surgical management is the treatment of choice to prevent the disastrous complications of large-bowel obstruction. We describe the case of a 92-year-old man who presented with symptoms and signs of large-bowel obstruction. Radiological investigation showed a large gallstone impacted in the sigmoid colon. Open enterolithotomy was undertaken relieving the obstruction and the patient made a full recovery. PMID- 20585362 TI - Acute appendicitis together with chylous ascites: is it a coincidence? AB - Acute chylous ascites is a rarely seen clinical picture, therefore, examination findings are often confused with acute appendicitis. To the best of our knowledge, there is no publication to date showing the occurrence of them together. This study presents the treatment plan for a 25-year-old male patient with both acute chylous ascites and appendicitis. Surgical findings were retrocaecal appendicitis, evident lymphangiectasia in the proximal segment of jejunum, and approximately 3 lt of chylous fluid. An appendectomy was performed and drainage was applied. Low-fat total parenteral nutrition (TPN) and octreotide treatment were administered for 7 days postoperatively. We also present a general review of some studies on chylous ascites, which have been published in the English language medical literature since 1910. PMID- 20585364 TI - Endosonography-guided pancreatic duct drainage for chronic pancreatitis: a case report and review. AB - A 50-year-old man was admitted to our department, complaining of epigastric pain and high fever. CT revealed a pseudocyst at the pancreatic head with upstream dilatation of the pancreatic duct (PD) and fluid collection surrounding the pancreas. Endosonography-guided PD drainage (ESPD) was performed because of unsuccessful ERCP. With a curved linear array echoendoscope, a 7.2 F catheter was placed in the PD. Laboratory data showed improvement in a few days and revealed disappearance of the fluid collection. Ten days after ESPD, a 7 F stent was placed in the PD via the puncture tract across the papilla of Vater followed by transpapillary replacement with a 10 F stent. CT showed a reduction in diameter of the PD and disappearance of the pseudocyst. ESPD is a feasible and useful procedure in selected patients with chronic pancreatitis showing stenosis of the main PD when transpapillary approach is impossible. PMID- 20585365 TI - Cavernous hemangioma of the rib: a rare diagnosis. AB - Hemangioma of the rib is an uncommon benign vascular tumour. A case of rib hemangioma in a 29-year-old woman is presented. Chest roentgenogram and computed tomography revealed a mass along the inner surface of the 7th left rib with bone destruction. She underwent resection of the 7th rib. The pathologic diagnosis was cavernous hemangioma. Hemangiomas of the rib are rare tumours but should be kept in mind in the differential diagnosis of rib tumours. PMID- 20585363 TI - Effect of Agaricus blazei Murill on the pulmonary tissue of animals with streptozotocin-induced diabetes. AB - The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Agaricus blazei Muril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.). Agaricus blazei Muril was administered daily starting 40 days after disease onset. A. Blazei was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening of A. Blazei detected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43 +/- 0.09; P < .001) as compared to the control group (0.18 +/- 0.02), followed by a reduction in the A. Blazei-treated group (0.33 +/- 0.04; P < .05). iNOS was found increased in the lung in diabetic rats and reduced in the A. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress and contributed to tissue recovery. PMID- 20585366 TI - A man with an umbilicated papule of the hand: what is your diagnosis? AB - Introduction. Ecthyma contagiosum is a zoonotic disease caused by the parapoxvirus that causes "sore mouth" in sheep and goats and orf in human. Case Presentation. A 61-year-old sheep farmer presented with a painful non-pruritic lesion on the left hand that had been present for approximately 5 weeks. Physical examination demonstrated a 1 cm pearly, umbilicated papule with raised borders. A biopsy showed an asymmetrical nodule with parakeratotic crust and acanthosis with thin epidermal strands extending deeply in the underlying dermis. Marked edema, capillary proliferation and extensive lymphocytic infiltration was also present. One red intranuclear inclusion was identified in an epidermal keratinocyte. A diagnosis of human orf (ecthyma contagiosum) was made. Conclusion. Infected sheep and freshly vaccinated sheep or goats are the reservoir for human infection. After an incubation period of 3-7 days, parapoxvirus infections produce 1-3 painful lesions measuring 1-2 cm in diameter. The natural history of the disease is complete resolution and no treatment is indicated. Prevention of echthyma contagiosum in ruminants through vaccination is thought to be the best way to control infection. PMID- 20585367 TI - Single incision laparoscopic colectomy: technical aspects, feasibility, and expected benefits. AB - Background. This paper studied technical aspects and feasibility of single incision laparoscopic colectomy (SILC). Methods. Bibliographic search was carried out up to October 2009 including original articles, case reports, and technical notes. Assessed criteria were techniques, operative time, scar length, conversion, complications, and hospitalization duration. Results. The review analyzed seventeen SILCs by seven surgical teams. A single port system was used by four teams. No team used the same laparoscope. Two teams used two laparoscopes. All teams used curved instruments. SILC time was 116 +/- 34 minutes. Final scar was longer than port incision (31 +/- 7 versus 24 +/- 8 mm; P = .036). No conversion was reported. The only complication was a bacteremia. Hospitalization was 5 +/- 2 days. Conclusion. SILC is feasible. A single incision around the umbilical scar represents cosmetic progress. Comparative studies are needed to assess potential abdominal wall and recovery benefits to justify the increased cost of SILC. PMID- 20585368 TI - Life-threatening clostridial sepsis in a postmenopausal patient with degenerating uterine leiomyoma. AB - Clostridium perfringens is a fulminant infection that affects patients with a high rate of morbidity and mortality. Fortunately, C. perfringens-associated sepsis and death in the gynecologic patient is rarely encountered. We report a case of intrauterine C. perfringens presenting as life-threatening sepsis in a postmenopausal patient. PMID- 20585369 TI - Pericardiectomy for pleuropericardial effusion complicating bacterial pneumonia. AB - Severe pericardial effusion is a rare complication of bacterial pneumonia and it usually disappears under medical treatment. Herein we report a case of a girl with a congenital immunodeficient syndrome and bacterial pneumonia, who developed recurrent and life-threatening pericardial effusion refractory to medical treatment. She was finally treated with pericardiectomy. PMID- 20585370 TI - Spontaneous Bacterial Pericarditis and Coronary Sinus Endocarditis Caused by Oxacillin-Susceptible Staphylococcus aureus. AB - This paper describes a case of a 44-year-old male patient previously healthy admitted with an unusual spontaneous acute bacterial pericarditis associated with coronary sinus mass. Two-dimensional echocardiography showed large loculated pericardial effusion with signs of diastolic restriction and an image suggesting vegetation in topography of the right atrium coronary sinus. Pericardial drainage, coronary sinus vegetation resection, and antibiotic therapy with Oxacillin were performed due to Oxacillin-susceptible Staphylococcus aureus identified on the pericardial effusion and blood culture. This is a rare condition and a unique combination of a spontaneous acute bacterial pericarditis with coronary sinus endocarditis without cardiac valve compromise. PMID- 20585372 TI - Hippocampal neurons keep track of two things--one moving, one not- simultaneously. PMID- 20585371 TI - Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop. AB - Invariant Natural Killer T cells (iNKT) are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR) loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells. PMID- 20585373 TI - Dynamic grouping of hippocampal neural activity during cognitive control of two spatial frames. AB - Cognitive control is the ability to coordinate multiple streams of information to prevent confusion and select appropriate behavioral responses, especially when presented with competing alternatives. Despite its theoretical and clinical significance, the neural mechanisms of cognitive control are poorly understood. Using a two-frame place avoidance task and partial hippocampal inactivation, we confirmed that intact hippocampal function is necessary for coordinating two streams of spatial information. Rats were placed on a continuously rotating arena and trained to organize their behavior according to two concurrently relevant spatial frames: one stationary, the other rotating. We then studied how information about locations in these two spatial frames is organized in the action potential discharge of ensembles of hippocampal cells. Both streams of information were represented in neuronal discharge-place cell activity was organized according to both spatial frames, but almost all cells preferentially represented locations in one of the two spatial frames. At any given time, most coactive cells tended to represent locations in the same spatial frame, reducing the risk of interference between the two information streams. An ensemble's preference to represent locations in one or the other spatial frame alternated within a session, but at each moment, location in the more behaviorally relevant spatial frame was more likely to be represented. This discharge organized into transient groups of coactive neurons that fired together within 25 ms to represent locations in the same spatial frame. These findings show that dynamic grouping, the transient coactivation of neural subpopulations that represent the same stream of information, can coordinate representations of concurrent information streams and avoid confusion, demonstrating neural-ensemble correlates of cognitive control in hippocampus. PMID- 20585374 TI - Incidence and reproduction numbers of pertussis: estimates from serological and social contact data in five European countries. AB - BACKGROUND: Despite large-scale vaccination programmes, pertussis has remained endemic in all European countries and has been on the rise in many countries in the last decade. One of the reasons that have been discussed for the failure of vaccination to eliminate the disease is continued circulation of the pathogen Bordetella pertussis by mostly asymptomatic and mild infections in adolescents and adults. To understand the impact of asymptomatic and undiagnosed infection on the transmission dynamics of pertussis we analysed serological data from five European countries in combination with information about social contact patterns from five of those countries to estimate incidence and reproduction numbers. METHODS AND FINDINGS: We compared two different methods for estimating incidence from individual data on IgG pertussis toxin (PT) titres. One method combines the cross-sectional surveys of titres with longitudinal information about the distribution of amplitude and decay rate of titres in a back-calculation approach. The second method uses age-dependent contact matrices and cross sectional surveys of IgG PT titres to estimate a next generation matrix for pertussis transmission among age groups. The next generation approach allows for computation of basic reproduction numbers for five European countries. Our main findings are that the seroincidence of infections as estimated with the first method in all countries lies between 1% and 6% per annum with a peak in the adolescent age groups and a second lower peak in young adults. The incidence of infections as estimated by the second method lies slightly lower with ranges between 1% and 4% per annum. There is a remarkably good agreement of the results obtained with the two methods. The basic reproduction numbers are similar across countries at around 5.5. CONCLUSIONS: Vaccination with currently used vaccines cannot prevent continued circulation and reinfection with pertussis, but has shifted the bulk of infections to adolescents and adults. If a vaccine conferring lifelong protection against clinical and subclinical infection were available pertussis could be eliminated. Currently, continuing circulation of the pathogen at a subclinical level provides a refuge for the pathogen in which it can evolve and adjust to infect vaccinated populations. Please see later in the article for the Editors' Summary. PMID- 20585376 TI - Erratum to: The Wide-Awake Approach to Dupuytren's Disease: Fasciectomy under Local Anesthetic with Epinephrine. AB - [This corrects the article DOI: 10.1007/s11552-009-9239-y.]. PMID- 20585375 TI - Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat. AB - Following trauma of the adult brain or spinal cord the injured axons of central neurons fail to regenerate or if intact display only limited anatomical plasticity through sprouting. Adult cortical neurons forming the corticospinal tract (CST) normally have low levels of the neuronal calcium sensor-1 (NCS1) protein. In primary cultured adult cortical neurons, the lentivector-induced overexpression of NCS1 induces neurite sprouting associated with increased phospho-Akt levels. When the PI3K/Akt signalling pathway was pharmacologically inhibited the NCS1-induced neurite sprouting was abolished. The overexpression of NCS1 in uninjured corticospinal neurons exhibited axonal sprouting across the midline into the CST-denervated side of the spinal cord following unilateral pyramidotomy. Improved forelimb function was demonstrated behaviourally and electrophysiologically. In injured corticospinal neurons, overexpression of NCS1 induced axonal sprouting and regeneration and also neuroprotection. These findings demonstrate that increasing the levels of intracellular NCS1 in injured and uninjured central neurons enhances their intrinsic anatomical plasticity within the injured adult central nervous system. PMID- 20585377 TI - Enhanced prefrontal serotonin 5-HT(1A) currents in a mouse model of Williams Beuren syndrome with low innate anxiety. AB - Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the hemizygous deletion of 28 genes on chromosome 7, including the general transcription factor GTF2IRD1. Mice either hemizygously (Gtf2ird1(+/-)) or homozygously (Gtf2ird1(-/-)) deleted for this transcription factor exhibit low innate anxiety, low aggression and increased social interaction, a phenotype that shares similarities to the high sociability and disinhibition seen in individuals with WBS. Here, we investigated the inhibitory effects of serotonin (5-HT) on the major output neurons of the prefrontal cortex in Gtf2ird1(-/-) mice and their wildtype (WT) siblings. Prefrontal 5-HT receptors are known to modulate anxiety like behaviors, and the Gtf2ird1(-/-) mice have altered 5-HT metabolism in prefrontal cortex. Using whole cell recording from layer V neurons in acute brain slices of prefrontal cortex, we found that 5-HT elicited significantly larger inhibitory, outward currents in Gtf2ird1(-/-) mice than in WT controls. In both genotypes, these currents were resistant to action potential blockade with TTX and were suppressed by the selective 5-HT(1A) receptor antagonist WAY-100635, suggesting that they are mediated directly by 5-HT(1A) receptors on the recorded neurons. Control experiments suggest a degree of layer and receptor specificity in this enhancement since 5-HT(1A) receptor-mediated responses in layer II/III pyramidal neurons were unchanged as were responses mediated by two other inhibitory receptors in layer V pyramidal neurons. Furthermore, we demonstrate GTF2IRD1 protein expression by neurons in layer V of the prefrontal cortex. Our finding that 5-HT(1A)-mediated responses are selectively enhanced in layer V pyramidal neurons of Gtf2ird1(-/-) mice gives insight into the cellular mechanisms that underlie reduced innate anxiety and increased sociability in these mice, and may be relevant to the low social anxiety and disinhibition in patients with WBS and their sensitivity to serotonergic medicines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689 010-9044-5) contains supplementary material, which is available to authorized users. PMID- 20585378 TI - Aging in fragile X syndrome. AB - Many studies have focused on the behavior and cognitive problems in young patients with fragile X syndrome (FXS), but there are no studies about the problems in aging for those with FXS. The discovery of the fragile X-associated tremor ataxia syndrome (FXTAS), a neurodegenerative disorder related to elevated FMR1-mRNA, in elderly men and some women with the premutation, intensified the need for aging studies in FXS. Approximately 40% of males with FXS have repeat size mosaicism and as a result, some of these individuals also have elevated levels of FMR1-mRNA which theoretically puts them at risk for FXTAS. Here, we have surveyed all of the aging patients with FXS that we have followed over the years to clarify the medical complications of aging seen in those with FXS. Data was collected from 62 individuals with the FXS full mutation (44 males; 18 females) who were at least 40 years old at their most recent clinical examination. We found that the five most frequent medical problems in these patients were neurological problems (38.7%), gastrointestinal problems (30.6%), obesity (28.8%), hypertension (24.2%) and heart problems (24.2%). Movement disorders were significantly different between males and females (38.6% vs.10.2%, p = 0.029). We did not find any differences in medical problems between those with a full mutation and those with mosaicism. Identification of medical problems associated with aging in FXS is important to establish appropriate recommendations for medical screening and treatment considerations. PMID- 20585379 TI - Phase-plate electron microscopy: a novel imaging tool to reveal close-to-life nano-structures. AB - After slow progress in the efforts to develop phase plates for electron microscopes, functional phase plate using thin carbon film has been reported recently. It permits collecting high-contrast images of close-to-life biological structures with cryo-fixation and without staining. This report reviews the state of the art for phase plates and what is innovated with them in biological electron microscopy. The extension of thin-film phase plates to the material-less type using electrostatic field or magnetic field is also addressed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12551 008-0006-z) contains supplementary material, which is available to authorized users. PMID- 20585380 TI - Software survey: VOSviewer, a computer program for bibliometric mapping. AB - We present VOSviewer, a freely available computer program that we have developed for constructing and viewing bibliometric maps. Unlike most computer programs that are used for bibliometric mapping, VOSviewer pays special attention to the graphical representation of bibliometric maps. The functionality of VOSviewer is especially useful for displaying large bibliometric maps in an easy-to-interpret way. The paper consists of three parts. In the first part, an overview of VOSviewer's functionality for displaying bibliometric maps is provided. In the second part, the technical implementation of specific parts of the program is discussed. Finally, in the third part, VOSviewer's ability to handle large maps is demonstrated by using the program to construct and display a co-citation map of 5,000 major scientific journals. PMID- 20585381 TI - Plasticity versus repeatability in seabird migratory behaviour. AB - Pelagic seabird populations can use several discrete wintering areas, but it is unknown if individuals use the same wintering area year after year. This would have consequences for their population genetic structure and conservation. We here study the faithfulness of individuals to a moulting area within and among years in a small pelagic seabird, the Thin-billed prion, which moult their primary feathers during the early part of the non-breeding period. According to stable carbon isotope ratios (delta(13)C) of these feathers, 90% of Thin-billed prions moult in Antarctic and 10% in South American waters. Repeated samples from individuals in 2 or 3 years indicated that several birds changed between Antarctic and South American moulting areas or vice versa. However, individuals moulting in an area in one year were more likely to do so again. Four out of five adults maintained highly conserved delta(13)C over the extended moulting period. One bird, however, had systematic changes in delta(13)C indicating latitudinal movements between the two areas during moult. Thus, the present data show that this seabird species has a highly flexible migratory strategy, not only at the population level, but also at the individual level, enabling these seabirds to exploit a highly unpredictable environment. PMID- 20585382 TI - Adaptation or constraint? Reference-dependent scatter in honey bee dances. AB - The waggle dance of the honey bee is used to recruit nest mates to a resource. Dancer bees, however, may indicate many directions within a single dance bout; we show that this scatter in honey bee dances is strongly dependent on the sensory modality used to determine a reference angle in the dance. Dances with a visual reference are more precise than those with a gravity reference. This finding undermines the idea that scatter is introduced into dances, which the bees could perform more precisely, in order to spread recruits out over resource patches. It also calls into question reported interspecific differences that had been interpreted as adaptations of the dance to different habitats. Our results support a non-adaptive hypothesis: that dance scatter results from sensory and performance constraints, rather than modulation of the scatter by the dancing bee. However, an alternative adaptive hypothesis cannot be ruled out. PMID- 20585383 TI - Metabolic state alters economic decision making under risk in humans. AB - BACKGROUND: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. METHODOLOGY/PRINCIPAL FINDINGS: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl ghrelin levels respectively. CONCLUSIONS/SIGNIFICANCE: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity. PMID- 20585384 TI - Born knowing: tentacled snakes innately predict future prey behavior. AB - BACKGROUND: Aquatic tentacled snakes (Erpeton tentaculatus) can take advantage of their prey's escape response by startling fish with their body before striking. The feint usually startles fish toward the snake's approaching jaws. But when fish are oriented at a right angle to the jaws, the C-start escape response translates fish parallel to the snake's head. To exploit this latter response, snakes must predict the future location of the fish. Adult snakes can make this prediction. Is it learned, or are tentacled snakes born able to predict future fish behavior? METHODS AND FINDINGS: Laboratory-born, naive snakes were investigated as they struck at fish. Trials were recorded at 250 or 500 frames per second. To prevent learning, snakes were placed in a water container with a clear transparency sheet or glass bottom. The chamber was placed over a channel in a separate aquarium with fish below. Thus snakes could see and strike at fish, without contact. The snake's body feint elicited C-starts in the fish below the transparency sheet, allowing strike accuracy to be quantified in relationship to the C-starts. When fish were oriented at a right angle to the jaws, naive snakes biased their strikes to the future location of the escaping fish's head, such that the snake's jaws and the fish's translating head usually converged. Several different types of predictive strikes were observed. CONCLUSIONS: The results show that some predators have adapted their nervous systems to directly compensate for the future behavior of prey in a sensory realm that usually requires learning. Instead of behavior selected during their lifetime, newborn tentacled snakes exhibit behavior that has been selected on a different scale- over many generations. Counter adaptations in fish are not expected, as tentacled snakes are rare predators exploiting fish responses that are usually adaptive. PMID- 20585385 TI - Direct visualization of protease action on collagen triple helical structure. AB - Enzymatic processing of extracellular matrix (ECM) macromolecules by matrix metalloproteases (MMPs) is crucial in mediating physiological and pathological cell processes. However, the molecular mechanisms leading to effective physiological enzyme-ECM interactions remain elusive. Only scant information is available on the mode by which matrix proteases degrade ECM substrates. An example is the enzymatic degradation of triple helical collagen II fragments, generated by the collagenase MMP-8 cleavage, during the course of acute inflammatory conditions by gelatinase B/MMP-9. As is the case for many other matrix proteases, it is not clear how MMP-9 recognizes, binds and digests collagen in this important physiological process. We used single molecule imaging to directly visualize this protease during its interaction with collagen fragments. We show that the initial binding is mediated by the diffusion of the protease along the ordered helix on the collagen (3/4) fragment, with preferential binding of the collagen tail. As the reaction progressed and prior to collagen degradation, gelatin-like morphologies resulting from the denaturation of the triple helical collagen were observed. Remarkably, this activity was independent of enzyme proteolysis and was accompanied by significant conformational changes of the working protease. Here we provide the first direct visualization of highly complex mechanisms of macromolecular interactions governing the enzymatic processing of ECM substrates by physiological protease. PMID- 20585386 TI - Sympatric and allopatric divergence of MHC genes in threespine stickleback. AB - Parasites can strongly affect the evolution of their hosts, but their effects on host diversification are less clear. In theory, contrasting parasite communities in different foraging habitats could generate divergent selection on hosts and promote ecological speciation. Immune systems are costly to maintain, adaptable, and an important component of individual fitness. As a result, immune system genes, such as those of the Major Histocompatibility Complex (MHC), can change rapidly in response to parasite-mediated selection. In threespine stickleback (Gasterosteus aculeatus), as well as in other vertebrates, MHC genes have been linked with female mating preference, suggesting that divergent selection acting on MHC genes might influence speciation. Here, we examined genetic variation at MHC Class II loci of sticklebacks from two lakes with a limnetic and benthic species pair, and two lakes with a single species. In both lakes with species pairs, limnetics and benthics differed in their composition of MHC alleles, and limnetics had fewer MHC alleles per individual than benthics. Similar to the limnetics, the allopatric population with a pelagic phenotype had few MHC alleles per individual, suggesting a correlation between MHC genotype and foraging habitat. Using a simulation model we show that the diversity and composition of MHC alleles in a sympatric species pair depends on the amount of assortative mating and on the strength of parasite-mediated selection in adjacent foraging habitats. Our results indicate parallel divergence in the number of MHC alleles between sympatric stickleback species, possibly resulting from the contrasting parasite communities in littoral and pelagic habitats of lakes. PMID- 20585387 TI - Quantifying the performance of individual players in a team activity. AB - BACKGROUND: Teamwork is a fundamental aspect of many human activities, from business to art and from sports to science. Recent research suggest that team work is of crucial importance to cutting-edge scientific research, but little is known about how teamwork leads to greater creativity. Indeed, for many team activities, it is not even clear how to assign credit to individual team members. Remarkably, at least in the context of sports, there is usually a broad consensus on who are the top performers and on what qualifies as an outstanding performance. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine how individual features can be quantified, and as a test bed for other team-based human activities, we analyze the performance of players in the European Cup 2008 soccer tournament. We develop a network approach that provides a powerful quantification of the contributions of individual players and of overall team performance. CONCLUSIONS/SIGNIFICANCE: We hypothesize that generalizations of our approach could be useful in other contexts where quantification of the contributions of individual team members is important. PMID- 20585388 TI - Statistical tests for associations between two directed acyclic graphs. AB - Biological data, and particularly annotation data, are increasingly being represented in directed acyclic graphs (DAGs). However, while relevant biological information is implicit in the links between multiple domains, annotations from these different domains are usually represented in distinct, unconnected DAGs, making links between the domains represented difficult to determine. We develop a novel family of general statistical tests for the discovery of strong associations between two directed acyclic graphs. Our method takes the topology of the input graphs and the specificity and relevance of associations between nodes into consideration. We apply our method to the extraction of associations between biomedical ontologies in an extensive use-case. Through a manual and an automatic evaluation, we show that our tests discover biologically relevant relations. The suite of statistical tests we develop for this purpose is implemented and freely available for download. PMID- 20585389 TI - IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis. AB - Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM) recovered from the lungs of mice undergoing cecal ligation and puncture (CLP) display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3) and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/-) mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response. PMID- 20585390 TI - Bronchus-associated lymphoid tissue (BALT) and survival in a vaccine mouse model of tularemia. AB - BACKGROUND: Francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant. METHODOLOGY/PRINCIPAL FINDINGS: Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensis and neisserial recombinant PorB as an adjuvant candidate. Then, mice were challenged via the same route with the F. tularensis attenuated live vaccine strain (LVS). Mouse survival and analysis of a number of immune parameters were conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infection presented prominent lymphoid aggregates in peribronchial and perivascular areas, consistent with the location of bronchus-associated lymphoid tissue (BALT). BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs). We also observed local production of antibody generating cells and homeostatic chemokines in BALT areas. CONCLUSIONS: These data indicate that PorB might be an optimal adjuvant candidate for improving the protective effect of F. tularensis antigens. The presence of BALT induced after intranasal challenge in vaccinated mice might play a role in regulation of local immunity and long-term protection, but more work is needed to elucidate mechanisms that lead to its formation. PMID- 20585391 TI - JAK2 V617F constitutive activation requires JH2 residue F595: a pseudokinase domain target for specific inhibitors. AB - The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 alphaC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the alphaC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type. PMID- 20585392 TI - The Src homology 2 domain-containing adapter protein B (SHB) regulates mouse oocyte maturation. AB - SHB (Src homology 2 domain-containing adapter protein B) is involved in receptor tyrosine kinase signaling. Mice deficient in the Shb gene have been found to exhibit a transmission ratio distortion with respect to inheritance of the Shb null allele among offspring and this phenomenon was linked to female gamete production. Consequently, we postulated that Shb plays a role for oocyte biology and thus decided to investigate oocyte formation, meiotic maturation, and early embryo development in relation to absence of the Shb gene. Oogenesis was apparently accelerated judging from the stages of oocyte development on fetal day 18.5 and one week postnatally in Shb -/- mice; but in adulthood ovarian follicle maturation was impaired in these mice. Completion of meiosis I (first polar body extrusion) was less synchronized, with a fraction of oocytes showing premature polar body extrusion in the absence of Shb. In vitro fertilization of mature oocytes isolated from Shb +/+, +/- and -/- mice revealed impaired early embryo development in the -/- embryos. Moreover, the absence of Shb enhanced ERK (extracellular-signal regulated kinase) and RSK (ribosomal S6 kinase) signaling in oocytes and these effects were paralleled by an increased ribosomal protein S6 phosphorylation and activation. It is concluded that SHB regulates normal oocyte and follicle development and that perturbation of SHB signaling causes defective meiosis I and early embryo development. PMID- 20585393 TI - The Werner syndrome protein suppresses telomeric instability caused by chromium (VI) induced DNA replication stress. AB - Telomeres protect the chromosome ends and consist of guanine-rich repeats coated by specialized proteins. Critically short telomeres are associated with disease, aging and cancer. Defects in telomere replication can lead to telomere loss, which can be prevented by telomerase-mediated telomere elongation or activities of the Werner syndrome helicase/exonuclease protein (WRN). Both telomerase and WRN attenuate cytotoxicity induced by the environmental carcinogen hexavalent chromium (Cr(VI)), which promotes replication stress and DNA polymerase arrest. However, it is not known whether Cr(VI)-induced replication stress impacts telomere integrity. Here we report that Cr(VI) exposure of human fibroblasts induced telomeric damage as indicated by phosphorylated H2AX (gammaH2AX) at telomeric foci. The induced gammaH2AX foci occurred in S-phase cells, which is indicative of replication fork stalling or collapse. Telomere fluorescence in situ hybridization (FISH) of metaphase chromosomes revealed that Cr(VI) exposure induced an increase in telomere loss and sister chromatid fusions that were rescued by telomerase activity. Human cells depleted for WRN protein exhibited a delayed reduction in telomeric and non-telomeric damage, indicated by gammaH2AX foci, during recovery from Cr(VI) exposure, consistent with WRN roles in repairing damaged replication forks. Telomere FISH of chromosome spreads revealed that WRN protects against Cr(VI)-induced telomere loss and downstream chromosome fusions, but does not prevent chromosome fusions that retain telomere sequence at the fusion point. Our studies indicate that environmentally induced replication stress leads to telomere loss and aberrations that are suppressed by telomerase mediated telomere elongation or WRN functions in replication fork restoration. PMID- 20585394 TI - Transforming growth factor beta 2 and heme oxygenase 1 genes are risk factors for the cerebral malaria syndrome in Angolan children. AB - BACKGROUND: Cerebral malaria (CM) represents a severe outcome of the Plasmodium falciparum infection. Recent genetic studies have correlated human genes with severe malaria susceptibility, but there is little data on genetic variants that increase the risk of developing specific malaria clinical complications. Nevertheless, susceptibility to experimental CM in the mouse has been linked to host genes including Transforming Growth Factor Beta 2 (TGFB2) and Heme oxygenase 1 (HMOX1). Here, we tested whether those genes were governing the risk of progressing to CM in patients with severe malaria syndromes. METHODOLOGY/PRINCIPAL FINDINGS: We report that the clinical outcome of P. falciparum infection in a cohort of Angolan children (n = 430) correlated with nine TGFB2 SNPs that modify the risk of progression to CM as compared to other severe forms of malaria. This genetic effect was explained by two haplotypes harboring the CM-associated SNPs (Pcorrec. = 0.035 and 0.036). In addition, one HMOX1 haplotype composed of five CM-associated SNPs increased the risk of developing the CM syndrome (Pcorrec. = 0.002) and was under-transmitted to children with uncomplicated malaria (P = 0.036). Notably, the HMOX1-associated haplotype conferred increased HMOX1 mRNA expression in peripheral blood cells of CM patients (P = 0.012). CONCLUSIONS/SIGNIFICANCE: These results represent the first report on CM genetic risk factors in Angolan children and suggest the novel hypothesis that genetic variants of the TGFB2 and HMOX1 genes may contribute to confer a specific risk of developing the CM syndrome in patients with severe P. falciparum malaria. This work may provide motivation for future studies aiming to replicate our findings in larger populations and to confirm a role for these genes in determining the clinical course of malaria. PMID- 20585395 TI - No association between oxytocin receptor (OXTR) gene polymorphisms and experimentally elicited social preferences. AB - BACKGROUND: Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. METHODOLOGY/PRINCIPAL FINDINGS: We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games. CONCLUSION: We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant. PMID- 20585396 TI - CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. AB - BACKGROUND: Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression. METHODOLOGY/PRINCIPAL FINDINGS: We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells. CONCLUSIONS/SIGNIFICANCE: This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs. PMID- 20585397 TI - Aerosol chemistry over a high altitude station at northeastern Himalayas, India. AB - BACKGROUND: There is an urgent need for an improved understanding of the sources, distributions and properties of atmospheric aerosol in order to control the atmospheric pollution over northeastern Himalayas where rising anthropogenic interferences from rapid urbanization and development is becoming an increasing concern. METHODOLOGY/PRINCIPAL FINDINGS: An extensive aerosol sampling program was conducted in Darjeeling (altitude approximately 2200 meter above sea level (masl), latitude 27 degrees 01'N and longitude 88 degrees 15'E), a high altitude station in northeastern Himalayas, during January-December 2005. Samples were collected using a respirable dust sampler and a fine dust sampler simultaneously. Ion chromatograph was used to analyze the water soluble ionic species of aerosol. The average concentrations of fine and coarse mode aerosol were found to be 29.5+/-20.8 microg m(-3) and 19.6+/-11.1 microg m(-3) respectively. Fine mode aerosol dominated during dry seasons and coarse mode aerosol dominated during monsoon. Nitrate existed as NH(4)NO(3) in fine mode aerosol during winter and as NaNO(3) in coarse mode aerosol during monsoon. Gas phase photochemical oxidation of SO(2) during premonsoon and aqueous phase oxidation during winter and postmonsoon were the major pathways for the formation of SO(4)(2-) in the atmosphere. Long range transport of dust aerosol from arid regions of western India was observed during premonsoon. The acidity of fine mode aerosol was higher in dry seasons compared to monsoon whereas the coarse mode acidity was higher in monsoon compared to dry seasons. Biomass burning, vehicular emissions and dust particles were the major types of aerosol from local and continental regions whereas sea salt particles were the major types of aerosol from marine source regions. CONCLUSIONS/SIGNIFICANCE: The year-long data presented in this paper provide substantial improvements to the heretofore poor knowledge regarding aerosol chemistry over northeastern Himalayas, and should be useful to policy makers in making control strategies. PMID- 20585399 TI - Gene flow and genetic diversity of a broadcast-spawning coral in northern peripheral populations. AB - Recently, reef-building coral populations have been decreasing worldwide due to various disturbances. Population genetic studies are helpful for estimating the genetic connectivity among populations of marine sessile organisms with metapopulation structures such as corals. Moreover, the relationship between latitude and genetic diversity is informative when evaluating the fragility of populations. In this study, using highly variable markers, we examined the population genetics of the broadcast-spawning coral Acropora digitifera at 19 sites in seven regions along the 1,000 km long island chain of Nansei Islands, Japan. This area includes both subtropical and temperate habitats. Thus, the coral populations around the Nansei Islands in Japan are northern peripheral populations that would be subjected to environmental stresses different from those in tropical areas. The existence of high genetic connectivity across this large geographic area was suggested for all sites (F(ST) < or = 0.033) although small but significant genetic differentiation was detected among populations in geographically close sites and regions. In addition, A. digitifera appears to be distributed throughout the Nansei Islands without losing genetic diversity. Therefore, A. digitifera populations in the Nansei Islands may be able to recover relatively rapidly even when high disturbances of coral communities occur locally if populations on other reefs are properly maintained. PMID- 20585398 TI - Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner. AB - HIV's ability to establish long-lived latent infection is mainly due to transcriptional silencing in resting memory T lymphocytes and other non dividing cells including monocytes. Despite an undetectable viral load in patients treated with potent antiretrovirals, current therapy is unable to purge the virus from these latent reservoirs. In order to broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as an HIV inhibitor and latent activator. Bryostatin revealed antiviral activity against R5- and X4-tropic viruses in receptor independent and partly via transient decrease in CD4/CXCR4 expression. Further, bryostatin at low nanomolar concentrations robustly reactivated latent viral infection in monocytic and lymphocytic cells via activation of Protein Kinase C (PKC) -alpha and -delta, because PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. Bryostatin specifically modulated novel PKC (nPKC) involving stress induced AMP Kinase (AMPK) inasmuch as an inhibitor of AMPK, compound C partially ablated the viral reactivation effect. Above all, bryostatin was non-toxic in vitro and was unable to provoke T-cell activation. The dual role of bryostatin on HIV life cycle may be a beneficial adjunct to the treatment of HIV especially by purging latent virus from different cellular reservoirs such as brain and lymphoid organs. PMID- 20585400 TI - How are the interests of incapacitated research participants protected through legislation? An Italian study on legal agency for dementia patients. AB - BACKGROUND: Patients with dementia may have limited capacity to give informed consent to participate in clinical research. One possible way to safeguard the patients' interests in research is the involvement of a proxy in the recruitment process. In Italy, the system of proxy is determined by the courts. In this study we evaluate the timing for appointment of a legal proxy in Italy and identify predictive variables of appointment. METHODOLOGY/PRINCIPAL FINDINGS: Subjects were recruited among the outpatients seeking medical advice for cognitive complaints at the Centre for Research and Treatment of Cognitive Dysfunctions, University of Milan, "Luigi Sacco" Hospital. The Centre was participating to the AdCare Study, a no-profit randomised clinical trial coordinated by the Italian National Institute of Health. The requirement that informed consent be given by a legal representative dramatically slowed down the recruitment process in AdCare, which was prematurely interrupted. The Centre for Research and Treatment of Cognitive Dysfunctions collected data on the timing required to appoint the legal representatives. Patients diagnosed with dementia and their caregivers were provided information on the Italian law on legal agency (law 6/2004). At each scheduled check-up the caregiver was asked whether she/he had applied to appoint a legal proxy for the patient and the time interval between the presentation of the law, the registration of the application at the law court chancellery and the sentence of appointment was registered. The study involved 169 demented patients. Seventy-eight patients (46.2%) applied to appoint a legal proxy. These subjects were usually younger, had been suffering from dementia for a longer time, had less than two children and made more use of memantine. The mean interval time between the presentation of the law and the patients' application to the law court chancellery was two months. The mean interval time between the patient's application to the law court chancellery and the sentence of appointment was four months. CONCLUSIONS/SIGNIFICANCE: In Italy the requirement that legal representatives be appointed by the courts slows down subjects' participation in research. Other procedures for legal agency of the incapacitated patients may be adopted, taking as examples other EU countries' systems. PMID- 20585401 TI - Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts. AB - BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL), significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM) mesenchymal stem cells (MSC) on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(-) Burkitt type BJAB, median survival = 46 days) and an aggressive (EBV(+) B lymphoblastoid SKW6.4, median survival = 27 days) behavior in nude-SCID mice. Intra-peritoneal (i.p.) injection of MSC (4 days after i.p. injection of lymphoma cells) significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days). Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i) MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii) MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL. PMID- 20585402 TI - Targeted genome-wide enrichment of functional regions. AB - Only a small fraction of large genomes such as that of the human contains the functional regions such as the exons, promoters, and polyA sites. A platform technique for selective enrichment of functional genomic regions will enable several next-generation sequencing applications that include the discovery of causal mutations for disease and drug response. Here, we describe a powerful platform technique, termed "functional genomic fingerprinting" (FGF), for the multiplexed genomewide isolation and analysis of targeted regions such as the exome, promoterome, or exon splice enhancers. The technique employs a fixed part of a uniquely designed Fixed-Randomized primer, while the randomized part contains all the possible sequence permutations. The Fixed-Randomized primers bind with full sequence complementarity at multiple sites where the fixed sequence (such as the splice signals) occurs within the genome, and multiplex amplify many regions bounded by the fixed sequences (e.g., exons). Notably, validation of this technique using cardiac myosin binding protein-C (MYBPC3) gene as an example strongly supports the application and efficacy of this method. Further, assisted by genomewide computational analyses of such sequences, the FGF technique may provide a unique platform for high-throughput sample production and analysis of targeted genomic regions by the next-generation sequencing techniques, with powerful applications in discovering disease and drug response genes. PMID- 20585403 TI - Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates. AB - Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure. PMID- 20585404 TI - Diagnostic accuracy and optimal use of three tests for tuberculosis in live badgers. AB - BACKGROUND: Accurate diagnosis of tuberculosis (TB) due to infection with Mycobacterium bovis is notoriously difficult in live animals, yet important if we are to understand the epidemiology of TB and devise effective strategies to limit its spread. Currently available tests for diagnosing TB in live Eurasian badgers (Meles meles) remain unvalidated against a reliable gold standard. The aim of the present study was to evaluate the diagnostic accuracy and optimal use of three tests for TB in badgers in the absence of a gold standard. METHODOLOGY/PRINCIPAL FINDINGS: A Bayesian approach was used to evaluate the diagnostic accuracy and optimal use of mycobacterial culture, gamma-interferon assay and a commercially available serological test using multiple samples collected from 305 live wild badgers. Although no single test was judged to be sufficiently sensitive and specific to be used as a sole diagnostic method, selective combined use of the three tests allowed guidelines to be formulated that allow a diagnosis to be made for individual animals with an estimated overall accuracy of 93% (range: 75% to 97%). Employing this approach in the study population of badgers resulted in approximately 13 out of 14 animals having their true infection status correctly classified from samples collected on a single capture. CONCLUSIONS/SIGNIFICANCE: This method of interpretation represents a marked improvement on the current procedure for diagnosing M. bovis infection in live badgers. The results should be of use to inform future test and intervention strategies with the aim of reducing the incidence of TB in free-living wild badger populations. PMID- 20585405 TI - Production and Roles of Glial Tissue Inhibitor of Metalloproteinases-1 in Human Immunodeficiency Virus-1-Associated Dementia Neuroinflammation: A Review. AB - PROBLEM STATEMENT: Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and its cognate targets, the Matrix Metalloproteinases (MMPs), were differentially expressed in human brain samples with or without HIV-1 infection or HIV-1 Encephalitis (HIVE). APPROACH: A through literature review demonstrated that cell culture models of Central Nervous System (CNS) cell types had been used to illustrate the intricate temporal patterns of TIMP-1/MMP expression, regulated by a variety of inflammatory cytokines. RESULTS: As MMPs and TIMP-1 can significantly altered the extracellular environment and cell signaling, the differential regulation of TIMP-1/MMP expression in neuroinflammation can impact neuronal function and survival in disease conditions. TIMP-1 pro-survival effects had been demonstrated in a variety of cell types including CNS neurons, protecting cells from a wide range of stress and insults. TIMP-1, also known to interact with non-MMP targets, altered cell behavior. In this review, we discussed the possibility that the upregulation of TIMP-1 by glia in acute neuroinflammation may be a neuroprotective response. CONCLUSION: It will be important to delineate the effects of TIMP-1 on neurons and identify receptors and downstream signaling pathways, in order to evaluate TIMP-1 as a therapeutic strategy for neuroinflammatory and neurodegenerative diseases. PMID- 20585406 TI - Face Fields and Microperimetry for Estimating the Location of Fixation in Eyes with Macular Disease. AB - Face field evaluation provides insights into the presence and location of the preferred retinal locus, as validated by comparisons with findings from microperimetry. This technique requires no special equipment and can be used in a clinic or at a person's home by clinicians and low vision rehabilitation specialists. PMID- 20585407 TI - HOW THE EAR WORKS - NATURE'S SOLUTIONS FOR LISTENING. PMID- 20585408 TI - Grandparents Raising Grandchildren in the United States: Changing Family Forms, Stagnant Social Policies. AB - As a consequence of increased divorce rates, the proliferation of single-parent families, and patterns of economic stagnation, parents are increasingly relying on extended family to care for children. In the past few decades, a substantial increase in the number of grandparents raising grandchildren has been observed within the United States. Grandparents who raise their grandchildren are particularly vulnerable, as are the grandchildren in their care; however, U.S. policy currently presents many barriers, gaps, and unintended consequences for grandparent caregivers. In this paper, we use two theoretical paradigms 1) structural lag and 2) the political economy of aging perspective to argue that U.S. policy has not kept pace with the reality of the family and - as a result - those families who are most vulnerable often receive the least support. We propose that as family forms become more diverse a redefinition of the family to one that is less bound by residence and biology, to one based more on function, will be required. PMID- 20585409 TI - Joint generalized estimating equations for multivariate longitudinal binary outcomes with missing data: An application to AIDS data. AB - In a large, prospective longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women, instead of a single outcome variable, there are multiple binary outcomes (e.g., abnormal heart rate, abnormal blood pressure, abnormal heart wall thickness) considered as joint measures of heart function over time. In the presence of missing responses at some time points, longitudinal marginal models for these multiple outcomes can be estimated using generalized estimating equations (GEE) (Liang and Zeger, 1986), and consistent estimates can be obtained under the assumption of a missing completely at random (MCAR) mechanism. When the missing data mechanism is missing at random (MAR), that is the probability of missing a particular outcome at a time-point depends on observed values of that outcome and the remaining outcomes at other time points, we propose joint estimation of the marginal models using a single modified GEE based on an EM-type algorithm. The proposed method is motivated by the longitudinal study of cardiac abnormalities in children born to HIV-infected women and analyses of these data are presented to illustrate the application of the method. Further, in an asymptotic study of bias, we show that under an MAR mechanism in which missingness depends on all observed outcome variables, our joint estimation via the modified GEE produces almost unbiased estimates, provided the correlation model has been correctly specified, whereas estimates from standard GEE can lead to substantial bias. PMID- 20585410 TI - Experimental investigation of cryogenic oscillating heat pipes. AB - A novel cryogenic heat pipe, oscillating heat pipe (OHP), which consists of an 4 * 18.5 cm evaporator, a 6 * 18.5 cm condenser, and 10 cm length of adiabatic section, has been developed and experimental characterization conducted. Experimental results show that the maximum heat transport capability of the OHP reached 380W with average temperature difference of 49 degrees C between the evaporator and condenser when the cryogenic OHP was charged with liquid nitrogen at 48% (v/v) and operated in a horizontal direction. The thermal resistance decreased from 0.256 to 0.112 while the heat load increased from 22.5 to 321.8 W. When the OHP was operated at a steady state and an incremental heat load was added to it, the OHP operation changed from a steady state to an unsteady state until a new steady state was reached. This process can be divided into three regions: (I) unsteady state; (II) transient state; and (III) new steady state. In the steady state, the amplitude of temperature change in the evaporator is smaller than that of the condenser while the temperature response keeps the same frequency both in the evaporator and the condenser. The experimental results also showed that the amplitude of temperature difference between the evaporator and the condenser decreased when the heat load increased. PMID- 20585411 TI - What's in View for Toddlers? Using a Head Camera to Study Visual Experience. AB - This article reports 2 experiments using a new method to study 18- to 24-month olds' visual experiences as they interact with objects. Experiment 1 presents evidence on the coupling of head and eye movements and thus the validity of the head camera view of the infant's visual field in the geometry of the task context. Experiment 2 demonstrates the use of this method in the naturalistic context of toy play with a parent. The results point to the embodied nature of toddlers' attentional strategies and to importance of hands and hand actions in their visual experience of objects. The head camera thus appears to be a promising method that, despite some limitations, will yield new insights about the ecology and content of young children's experiences. PMID- 20585412 TI - INTEGRATING MULTI-SCALE BLOB/CURVILINEAR DETECTOR TECHNIQUES AND MULTI-LEVEL SETS FOR AUTOMATED SEGMENTATION OF STEM CELL IMAGES. AB - Studies of differentiation abilities of stem cells have been attracting a lot of attention over the last years. Microscopy can be used to record details of the differentiation process of stem cells under different perturbations and is an important tool for studying stem cell differentiation. Since it is infeasible to quantitatively analyze a huge amount of image data manually, automated image analysis systems are urgently needed. However, the complicated morphological appearances of stem cells are challenging to the existing segmentation methods. Herein, we propose a new, automated scheme for stem cell segmentation. This scheme first uses the multi-scale blob and curvilinear structure detectors to delineate the skeletons of stem cells quickly and then segment out stem cells by refining the skeletons to the cell boundaries using multi-level sets. The initial experimental results indicate the effectiveness of the proposed scheme. PMID- 20585413 TI - An Image Based System Biology Approach for Alzheimer's Disease Pathway Analysis. AB - We report multifactorial analysis of candidate mechanisms of Alzheimer's disease utilizing high content analysis, gene expression microarray, and linear regression model to integrate neuronal imaging data with hippocampal gene expression data. Our analysis led to the identification of several genes that may contribute to different image traits or phenotypes in the amyloid-beta (Abeta) injured neurons. Gene network and biological pathways analysis for those genes were further analyzed and led to several novel pathways that may contribute to amyloid plaque triggered neurite loss. PMID- 20585414 TI - The Design and Synthesis of Highly Branched and Spherically Symmetric Fluorinated Macrocyclic Chelators. AB - Two novel, highly fluorinated macrocyclic chelators with highly branched and spherically symmetric fluorocarbon moieties have been designed and efficiently synthesized. This is achieved by conjugating a spherically symmetric fluorocarbon moiety to the macrocyclic chelator DOTA, with or without a flexible oligo oxyethylene linker between these two parts. As a result of the spherical symmetry, all 27 fluorine atoms in each fluorinated chelator give a sharp singlet (19)F NMR signal. The hydrophilicity and the (19)F relaxation behavior of fluorinated chelators can be modulated by the insertion of a flexible linker between the fluorocarbon moiety and the macrocyclic linker. These chelators serve as prototypes for (1)H-(19)F dual-nuclei magnetic resonance imaging agents. PMID- 20585415 TI - MINIMIZING THE RISK OF PREGNANCY, SEXUALLY TRANSMITTED DISEASES, AND HIV AMONG INCARCERATED ADOLESCENT GIRLS: Identifying Potential Points of Intervention. AB - Delinquent girls are at elevated risk for unplanned pregnancy and sexually transmitted diseases when compared with non-delinquent peers. Participants-234 incarcerated female juveniles-completed demographic, individual, partner, peer, and family measures and were tested for sexually transmitted diseases. Disease rates were as follows: chlamydia (20%), gonorrhea (4%), and syphilis (1%). Stepwise multiple linear regression analysis assessed the relationship of the predictor variable sets with sexual risk. Demographic and individual variables had the strongest associations with risk. Peer, partner, or family variables did not account for significant additional variance. The results suggest that an intervention could be delivered during the window of opportunity during the girls' incarceration, changing their knowledge, attitudes, and skills that are implicated in risky sexual behavior before they are released back into the community. PMID- 20585416 TI - The midline, oral ectoderm, and the arch-0 problem. AB - In most versions of theories of the segmentation of the vertebrate head, a premandibular segment is present rostral to the jaw-forming mandibular segment. These theories posit that in ancient fishes this segment included a gill and a gill-supporting skeleton, which then was modified to support the anterior brain. However, we find no recent evidence for existence of such a premandibular segment. Rather, new findings from studies of fate mapping and gene expression show that the "premandibular" territory is in fact the maxillary region of the mandibular arch. A signaling cascade, beginning with dorsal midline mesoderm in the gastrula and relayed through neural ectoderm and then oral ectoderm, greatly expands the skeletal derivatives of maxillary neural crest in a manner fully consistent with the Gans-Northcutt theory of the vertebrate new head. PMID- 20585418 TI - Web-based instruction on substance abuse and drug diversion. AB - OBJECTIVES: To develop a pilot study to assess the effectiveness of a Web-based educational module on enhancing understanding of substance abuse and drug diversion, and to assess students' abilities and confidence in applying the information. DESIGN: A Web-based instructional module was presented to students enrolled in their second pre-professional year, and students were informed that it was part of a research study. Knowledge was tested using 10 pre- and post module questions. Students were also presented with 5 survey questions assessing abilities related to the learning objectives. ASSESSMENT: The median percentage of correct responses increased from 60% (Interquartile range [IQR] 20%) for the pre-module questions to 90% (IQR = 10%) for the post-module questions. The median percent gain in knowledge was 20% (IQR = 20%) which was significant (p < 0.0001). CONCLUSIONS: Web-based instruction is an alternative method for engaging students in course content. We found that 59% of our pilot study group worked in a pharmacy. From the success of the pilot study, the module was implemented as an extra credit assignment in a required course to provide a foundation for developing professional responsibility. PMID- 20585419 TI - Current events project in a pharmacotherapy course. AB - OBJECTIVE: To implement and assess a current events project added to the curriculum of a pharmacotherapy course in a doctor of pharmacy (PharmD) program. DESIGN: Third-year PharmD students researched a current event topic related to infectious diseases and prepared a written and verbal summary that was presented to their classmates. ASSESSMENT: Scores on course examinations and quizzes to assess students' knowledge of current events material were equal to or better than non-current events material. Based upon a student self-assessment survey, this active-learning activity increased students' awareness of current events related to pharmacy practice, and their understanding of the process to prepare and present information to a group in a statistically significant manner. There was a positive but not significant improvement in students' desire to prepare and present information to a group; ability to evaluate, organize, and present information in a written report; and ability to verbally present material to a group. CONCLUSION: The addition of a current events presentation as an active learning activity significantly increased students' awareness of current events related to pharmacy practice and their understanding of the process to prepare and present information to a group. PMID- 20585420 TI - Web-based portfolios for pharmaceutical care plans during advanced pharmacy practice experiences. AB - OBJECTIVE: To implement and assess a Web-based patient care portfolio system for development of pharmaceutical care plans by students completing advanced pharmacy practice experiences (APPEs) throughout a statewide preceptor network. DESIGN: Using a Web database, students in APPEs documented 6 patient cases within 5 disease state categories. Through discussion of the disease states and inclusion of patient information such as problems, desired outcomes, and interventions, a complete pharmaceutical care plan was developed for each patient. ASSESSMENT: Student interventions were compared by geographical regions to assess continuity of patient care activities by students. Additionally, students completed an evaluation of the portfolio course to provide feedback on the portfolio process. Students documented an average of 1.8 therapeutic interventions per patient case and documented interventions in all geographical regions. The majority of students indicated that the portfolio process improved their ability to develop a pharmaceutical care plan. CONCLUSION: The Web-based patient care portfolio process assisted with documentation of compliance with Accreditation Council of Pharmacy Education (ACPE) standards and College of Pharmacy Competency Statements. Students indicated the portfolio process was beneficial in developing skills needed for creating pharmaceutical care plans. PMID- 20585421 TI - Pharmacy student knowledge and communication of medication errors. AB - OBJECTIVES: To describe and evaluate pharmacy students' knowledge of and comfort in communicating, managing, and preventing medication errors. METHODS: Using a cross-sectional design, a survey instrument was administered to fifth-year pharmacy students. The survey instrument included both open- and close-ended questions to describe and examine factors associated with knowledge and comfort in communication of medication errors. RESULTS: Survey instruments were completed by 93 students (90% response rate). Nearly 80% reported not having received training in communicating medication errors. The perception of having more adequate training was related to greater knowledge in the communication of medication errors (p < or = 0.001). Knowledge was also associated with students having greater comfort in communicating medication errors (p < or = 0.05). CONCLUSIONS: The need and value of additional training for pharmacy students in communicating medication errors was demonstrated. Educational interventions should be developed to provide consistent instruction on these communication issues. PMID- 20585422 TI - Pharmacy students' perceptions and emotional responses to aggressive incidents in pharmacy practice. AB - OBJECTIVE: To explore pharmacy students' experiences with and perceptions of aggressive incidents in pharmacy practice. METHODS: Data were taken from a survey completed by second-year pharmacy (P2) students and analyzed using a retrospective, cross-sectional design. Survey items were adapted using the following scales: Perception of Aggression Survey (POAS), List of Aggressive Incidents experienced by mental health staff, and List of Emotions experienced by nurses. RESULTS: The majority of respondents did not identify aggression as normal, instead perceiving it as a violent reaction and functional. The 3 most frequent aggressive incidents experienced were: verbal abuse to face (40%); verbal abuse on the phone (39%); and refusal to cooperate with instructions (34%). The 3 most frequent emotions reported were: frustration (70%), empathy (65%), and no pride in their profession (70% rarely-never). CONCLUSION: Pharmacy students reported experiencing aggressive incidents with patients in person and on the phone, and with patients not following instructions. Preparing future pharmacists in techniques to address and resolve patients' aggression must become a priority for pharmacy academia and further research in this area is needed. PMID- 20585423 TI - Assessment of pharmacy student professionalism across a curriculum. AB - OBJECTIVES: To evaluate changes in professionalism across the curriculum among pharmacy students in different classes. METHODS: A professionalism instrument was administered early in the first (P1) year, upon completing the introductory pharmacy practice experiences (IPPE) near the end of the second (P2) year, and upon completing the advanced pharmacy practice experiences (APPE) at the end of the fourth (P4) year. RESULTS: The professionalism scale and its subscales were compared for the 3 time points for the class of 2009. Significant differences were noted in professionalism scores between the P1 and P4 years and for altruism, accountability, and honor/integrity subscale scores for the class of 2009. No significant differences were noted when the scores for 4 P1 classes, and 3 P2 classes were compared. CONCLUSION: An increase in professionalism scores and altruism, accountability, and honor/integrity scores was demonstrated, providing evidence that the curricular and co-curricular activities in the school of pharmacy helped develop professionalism in the class of 2009 students. PMID- 20585424 TI - Student learning: perception versus reality. PMID- 20585425 TI - Performance improvement in pharmacy education. PMID- 20585426 TI - A hand and glove approach to pharmacy experiential education and residency training. PMID- 20585427 TI - Quantitative assessment of assisted problem-based learning in a pharmaceutics course. AB - OBJECTIVES: To assess the effectiveness of assisted problem-based learning (PBL) compared to a didactic approach in a pharmaceutics course. DESIGN: Data were collected over 7 offerings of the course. In the first half of the semester about half of the students (PBL1) learned in a PBL format while the other students (PBL2) received didactic lectures. In the second half of the semester, the teaching methods were reversed. ASSESSMENT: Performance on the midterm examination and a comprehensive final examination was used to assess the effect of PBL. Over the 7-year period, PBL1 students scored significantly higher on the midterm examinations. Scores on the final examinations did not differ significantly, but PBL2 students had a higher mean score on questions based on material from the second half of the semester. CONCLUSIONS: PBL produced a short term (weeks) improvement in learning and our results suggest that the effect may persist in the medium term (months). PMID- 20585428 TI - Reflections on the first three years as a junior faculty member. PMID- 20585429 TI - Pharmacy education in India. AB - Pharmacy education in India traditionally has been industry and product oriented. In contrast to the situation in developed nations, graduate pharmacists prefer placements in the pharmaceutical industry. To practice as a pharmacist in India, one needs at least a diploma in pharmacy, which is awarded after only 2 years and 3 months of pharmacy studies. These diploma-trained pharmacists are the mainstay of pharmacy practice. The pharmacy practice curriculum has not received much attention. In India, there has been a surge in the number of institutions offering pharmacy degrees at various levels and a practice-based doctor of pharmacy (PharmD) degree program was started in some private institutions in 2008. However, relatively little information has been published describing the current status of complex pharmacy education of India. In this paper we describe pharmacy education in India and highlight major issues in pharmacy practice including deficiencies in curriculum. The changing face of the profession is discussed, including the establishment of the PharmD program. The information presented in this paper may stimulate discussion and critical analysis and planning, and will be of value in further adaptation of the pharmacy education to desired educational outcomes. PMID- 20585430 TI - Wellness: Pharmacy education's role and responsibility. AB - The root cause of most chronic diseases in America is self-inflicted through an unhealthy lifestyle including poor diet, insufficient exercise, inability to maintain a healthy weight, tobacco use, and excessive alcohol consumption. Americans' ability to adhere to healthy lifestyles appears to be declining.1,2 The pharmacy profession, while positioned to provide an answer to this problem, has done little. In addition, academic pharmacy's primary focus is on drugs and diseases with limited instruction in the area of wellness. It is time for pharmacy education to step up and take a leadership role in enhancing the wellness of Americans. PMID- 20585431 TI - A motivational interviewing course for pharmacy students. AB - OBJECTIVE: To create, implement, and evaluate a pharmacy course on motivational interviewing. DESIGN: A 3-hour elective course was created to train doctor of pharmacy (PharmD) students in brief patient-centered motivational interviewing counseling strategies that have proven effective with the types of health issues most commonly addressed in pharmacy settings. Students were assisted in developing their skills through required readings, interactive lectures, in-class demonstrations and practice sessions, out of class skills practice, one-on-one supervision provided by doctoral level clinical health psychology students, and written reflections on each class session. ASSESSMENT: Students demonstrated significant improvement in motivational interviewing skills and a high level of motivation for and confidence in using these skills in their future practice. Students overall assessment of the course and supervision process was highly positive. CONCLUSION: This patient-centered counseling skills course was feasible and produced improvements in PharmD students' counseling skills and increased their motivation and confidence to use motivational interviewing skills in their future communications with patients. PMID- 20585432 TI - Using electronic medical records to teach patient-centered care. AB - OBJECTIVE: To develop, implement, and evaluate the use of electronic medical records (EMRs) in disease state management activities to teach pharmacy students patient-centered care skills. DESIGN: Faculty created 12 patient cases and an EMR for each simulated patient. Students used the information in the EMR to confirm the presence of a disease in their patient; to design and monitor an evidence based patient-centered care plan, and document their assessment, medication, and monitoring recommendations; and to follow up in a SOAP (subjective, objective, assessment, plan) note format within the EMR. ASSESSMENT: A precourse and postcourse survey instrument was administered to assess students' perceived gains in knowledge and attitudes regarding the use of EMRs for learning patient centered care skills. A grading rubric was used to evaluate each SOAP note. CONCLUSION: Implementation of disease state management activities involving EMRs improved pharmacy students' patient care skills. PMID- 20585433 TI - The teaching mission of pharmacy practice: promoting academic pharmacy careers early on. PMID- 20585434 TI - Postgraduate programs in clinical pharmacy and pharmacy practice: are we heading in the right direction? PMID- 20585435 TI - Education, postgraduate training, board certification, and experience requirements in advertisements for clinical faculty positions. AB - OBJECTIVES: To compare requirements for pharmacy practice faculty positions in advertisements from 2002 through 2006 to those reported from 1990 through 1994. METHODS: Positions advertised from January 2002 through December 2006 in 3 newsletters and journals were evaluated for required or preferred degree, completion of residencies and/or fellowships, years of work experience, board certification, and other postgraduate training and education. Advertisements were separated by tenure-eligibility and rank. RESULTS: Of 426 advertisements for faculty members, 77% required additional training, including residencies and fellowships or their equivalent in experience. Board certification was required in only 0.9% but preferred in 11%. Advertisements for tenure-eligible positions did not have more extensive requirements than nontenured, nor did upper vs. lower rank. CONCLUSIONS: Compared to 1996, the number of advertisements requiring postgraduate training to secure a faculty position almost doubled. Whether the qualifications of faculty members recruited match the requirements is unknown. PMID- 20585436 TI - Job location decisions of pharmacy graduates in British Columbia. AB - OBJECTIVES: To determine the factors influencing pharmacy graduates' selection of their first professional job location. METHODS: A survey was conducted of the 2007 graduating class of the University of British Columbia, examining hometown location, community and workplace factors, personal relationships, financial factors, and leisure activities. Responses were analyzed to determine whether community size or demographic characteristics affected the degree to which each factor influenced the job location decision. RESULTS: The majority of graduates moved from their hometowns to larger communities, mainly to the largest city in British Columbia. Most of those taking jobs in rural and remote communities grew up in or near those communities, and were more influenced by community size and anticipated working conditions, and less influenced by access to cultural and social activities, than their urban counterparts. CONCLUSIONS: The admission of students from rural and remote communities is modestly effective in ensuring a supply of pharmacists for these areas. PMID- 20585437 TI - Factors influencing pharmacy students' choice of major and its relationship to anticipatory socialization. AB - OBJECTIVES: To determine factors that influenced students' choice of pharmacy as a major and assess relationships between these factors and anticipatory socialization. METHODS: Two hundred fifteen freshman and sophomore students enrolled in a 0-6 doctor of pharmacy program completed a survey instrument on which they rated 6 motivational factors in their decision to major in pharmacy and answered questions related to anticipatory socialization. Bivariate and multivariate analyses were used to answer the research questions posed. RESULTS: Female students ranked desire to help others as a stronger motivating factor in their decision to pursue a career in pharmacy than did male students. Caucasian students rated providing more career opportunities and providing an entry-level doctorate as stronger motivating factors for pursuing pharmacy than did Asian students. Asian students had lower levels of anticipatory socialization than other students. Students with higher levels of motivation had higher levels of anticipatory socialization. CONCLUSION: Results of this study provide further insight into effective recruiting strategies and recommendations for improved pharmacy education. PMID- 20585438 TI - The dose window for radiation-induced protective adaptive responses. AB - Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low dose rate exposure. However, these thresholds for protection are not a fixed function of total dose, but also vary with dose rate, additional radiation or non-radiation stressors, tissue type and p53 functional status. Exposures above the upper threshold are generally detrimental, while exposures below the lower threshold may or may not increase either cancer or non-cancer disease risk. PMID- 20585439 TI - Immunological mechanism of the low-dose radiation-induced suppression of cancer metastases in a mouse model. AB - According to the doctrine underlying the current radiation protection regulations each, no matter how small, exposure to ionizing radiation may be carcinogenic. However, numerous epidemiological observations demonstrate that cancer incidence and/or mortality are not elevated among inhabitants of the high- versus low natural-background radiation areas and homes. Results of our own and other authors' studies described in this paper bear testimony to the possibility that stimulation of the anti-neoplastic immune surveillance mediated by NK lymphocytes and activated macrophages explains, at least partially, the accumulating epidemiological and experimental evidence indicating that low-level exposures to the low-linear energy transfer (LET) radiation inhibit the development of spontaneous and artificial metastases in humans and laboratory animals, respectively. The results presented also suggest the possibility of using low level X- and gamma-ray exposures to cure cancer and to prevent cancer metastases. For a broader perspective, the results presented may help towards relaxing the current radiation protection regulations, especially as they apply to diagnostic and therapeutic exposures of patients to the indicated forms of radiation. PMID- 20585440 TI - Low-dose cancer risk modeling must recognize up-regulation of protection. AB - IONIZING RADIATION PRIMARILY PERTURBS THE BASIC MOLECULAR LEVEL PROPORTIONAL TO DOSE, WITH POTENTIAL DAMAGE PROPAGATION TO HIGHER LEVELS: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation. Physical-static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins; - molecular repair, especially of DNA; - removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses, - followed by replacement of lost elements. Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms. Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from non-radiogenic endogenous sources. Adaptive protections have a maximum after single tissue absorbed doses around 100 to 200 mSv and disappear with higher doses. Low dose rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals. Adaptive protection preventing only about 2 - 3 % of endogenous life-time cancer risk would fully balance a calculated induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect. Low dose-risk modeling must recognize up-regulation of protection. PMID- 20585441 TI - Special issue introduction. PMID- 20585442 TI - The healthy worker effect and nuclear industry workers. AB - The linear no-threshold (LNT) dose-effect relationship has been consistently used by most radiation epidemiologists to estimate cancer mortality risk. The large scattering of data by International Agency for Research on Cancer, IARC (Vrijheid et al. 2007; Therry-Chef et al. 2007; Cardis et al. 2007), interpreted in accordance with LNT, has been previously demonstrated (Fornalski and Dobrzynski 2009). Using conventional and Bayesian methods the present paper demonstrates that the standard mortality ratios (SMRs), lower in the IARC cohort of exposed nuclear workers than in the non exposed group, should be considered as a hormetic effect, rather than a healthy worker effect (HWE) as claimed by the IARC group. PMID- 20585443 TI - Observations on the Chernobyl Disaster and LNT. AB - The Chernobyl accident was probably the worst possible catastrophe of a nuclear power station. It was the only such catastrophe since the advent of nuclear power 55 years ago. It resulted in a total meltdown of the reactor core, a vast emission of radionuclides, and early deaths of only 31 persons. Its enormous political, economic, social and psychological impact was mainly due to deeply rooted fear of radiation induced by the linear non-threshold hypothesis (LNT) assumption. It was a historic event that provided invaluable lessons for nuclear industry and risk philosophy. One of them is demonstration that counted per electricity units produced, early Chernobyl fatalities amounted to 0.86 death/GWe year), and they were 47 times lower than from hydroelectric stations ( approximately 40 deaths/GWe-year). The accident demonstrated that using the LNT assumption as a basis for protection measures and radiation dose limitations was counterproductive, and lead to sufferings and pauperization of millions of inhabitants of contaminated areas. The projections of thousands of late cancer deaths based on LNT, are in conflict with observations that in comparison with general population of Russia, a 15% to 30% deficit of solid cancer mortality was found among the Russian emergency workers, and a 5% deficit solid cancer incidence among the population of most contaminated areas. PMID- 20585445 TI - A novel, single algorithm approach to predict acenocoumarol dose based on CYP2C9 and VKORC1 allele variants. AB - The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an "acenocoumarol-dose genotype score" (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (> 28 mg/week) compared with the low-dose (< 7 mg/week) group (mean(SEM) of 84.1+/-3.4 vs. 62.2+/-4.8, P = 0.008). An AGS > 70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112 10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti coagulation. PMID- 20585444 TI - Radiation hormesis: historical perspective and implications for low-dose cancer risk assessment. AB - Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID- 20585446 TI - Live recombinant Salmonella Typhi vaccines constructed to investigate the role of rpoS in eliciting immunity to a heterologous antigen. AB - We hypothesized that the immunogenicity of live Salmonella enterica serovar Typhi vaccines expressing heterologous antigens depends, at least in part, on its rpoS status. As part of our project to develop a recombinant attenuated S. Typhi vaccine (RASTyV) to prevent pneumococcal diseases in infants and children, we constructed three RASTyV strains synthesizing the Streptococcus pneumoniae surface protein PspA to test this hypothesis. Each vector strain carried ten engineered mutations designed to optimize safety and immunogenicity. Two S. Typhi vector strains (chi9639 and chi9640) were derived from the rpoS mutant strain Ty2 and one (chi9633) from the RpoS(+) strain ISP1820. In chi9640, the nonfunctional rpoS gene was replaced with the functional rpoS gene from ISP1820. Plasmid pYA4088, encoding a secreted form of PspA, was moved into the three vector strains. The resulting RASTyV strains were evaluated for safety in vitro and for immunogenicity in mice. All three RASTyV strains were similar to the live attenuated typhoid vaccine Ty21a in their ability to survive in human blood and human monocytes. They were more sensitive to complement and were less able to survive and persist in sewage and surface water than their wild-type counterparts. Adult mice intranasally immunized with any of the RASTyV strains developed immune responses against PspA and Salmonella antigens. The RpoS(+) vaccines induced a balanced Th1/Th2 immune response while the RpoS(-) strain chi9639(pYA4088) induced a strong Th2 immune response. Immunization with any RASTyV provided protection against S. pneumoniae challenge; the RpoS(+) strain chi9640(pYA4088) provided significantly greater protection than the ISP1820 derivative, chi9633(pYA4088). In the pre-clinical setting, these strains exhibited a desirable balance between safety and immunogenicity and are currently being evaluated in a Phase 1 clinical trial to determine which of the three RASTyVs has the optimal safety and immunogenicity profile in human hosts. PMID- 20585447 TI - Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. AB - BACKGROUND: Histone deacetylase inhibitors (HDACis) re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process. METHODOLOGY/PRINCIPAL FINDINGS: Applying Analysis of Functional Annotation (AFA) on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR) DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs. CONCLUSIONS/SIGNIFICANCE: Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC inhibition could also be attributed to several other pathways besides the ones investigated in this study. However, our study does provide insights into the mechanism that governs downregulation of HR DNA repair genes upon HDAC inhibition, which can lead to rationale usage of HDACis in the clinics. PMID- 20585448 TI - Oncoproteomic analysis reveals co-upregulation of RELA and STAT5 in carboplatin resistant ovarian carcinoma. AB - BACKGROUND: Ovarian cancer is one of the most lethal types of female malignancy. Although most patients are initially responsive to platinum-based chemotherapy, almost all develop recurrent chemoresistant tumors and succumb to their diseases. Elucidating the pathogenesis underlying drug resistance is fundamental to the development of new therapeutics, leading to improved clinical outcomes in these patients. METHODS AND FINDINGS: We compared the proteomes of paired primary and recurrent post-chemotherapy ovarian high-grade serous carcinomas from nine ovarian cancer patients using CIEF/Nano-RPLC coupled with ESI-Tandem MS. As compared to their primary tumors, more than half of the recurrent tumors expressed higher levels of several proteins including CP, FN1, SYK, CD97, AIF1, WNK1, SERPINA3, APOD, URP2, STAT5B and RELA (NF-kappaB p65), which were also validated by quantitative RT-PCR. Based on shRNA screening for the upregulated genes in in vitro carboplatin-resistant cells, we found that simultaneous knockdown of RELA and STAT5B was most effective in sensitizing tumor cells for carboplatin treatment. Similarly, the NF-kappaB inhibitor, BMS-345541, and the STAT5 inhibitor, Dasatinib, significantly enhanced cell sensitivity to carboplatin. Moreover, both RELA and STAT5 are known to bind to the promoter region of Bcl-X, regulating its promoter activity. In this regard, augmented Bcl xL expression was detected in carboplatin-resistant cells. Combined ectopic expression of RELA and STAT5B enhanced Bcl-xL promoter activity while treatment with BMS-345541 and Dasatinib decreased it. Chromatin immunoprecipitation of the Bcl-X promoter region using a STAT5 antibody showed induction of RELA and STAT5 DNA-binding segments both in naive cells treated with a high concentration of carboplatin as well as in carboplatin-resistant cells. CONCLUSIONS: Proteomic analysis identified RELA and STAT5 as two major proteins associated with carboplatin resistance in ovarian tumors. Our results further showed that NF kappaB and STAT5 inhibitor could sensitize carboplatin-resistant cells and suggest that such inhibitors can be used to benefit patients with carboplatin resistant recurrent ovarian cancer. PMID- 20585449 TI - The involvement of IL-17A in the murine response to sub-lethal inhalational infection with Francisella tularensis. AB - BACKGROUND: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell mediated immunity and IFNgamma in the host response to Francisella tularensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary gammadelta and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1xLD(50) resulted in a fatal disease. CONCLUSION: In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia. PMID- 20585450 TI - Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols. AB - BACKGROUND: Nitric oxide (NO) has long been recognized to affect muscle contraction, both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibrillar proteins remain unknown. Here we report that nitrogen oxides directly regulate striated muscle myosins. PRINCIPAL FINDINGS: Exposure of skeletal and cardiac myosins to physiological concentrations of nitrogen oxides, including the endogenous nitrosothiol S-nitroso-L-cysteine, reduced the velocity of actin filaments over myosin in a dose-dependent and oxygen-dependent manner, caused a doubling of force as measured in a laser trap transducer, and caused S nitrosylation of cysteines in the myosin heavy chain. These biomechanical effects were not observed in response to S-nitroso-D-cysteine, demonstrating specificity for the naturally occurring isomer. Both myosin heavy chain isoforms in rats and cardiac myosin heavy chain from human were S-nitrosylated in vivo. SIGNIFICANCE: These data show that nitrosylation signaling acts as a molecular "gear shift" for myosin--an altogether novel mechanism by which striated muscle and cellular biomechanics may be regulated. PMID- 20585451 TI - Immune response to Lactobacillus plantarum expressing Borrelia burgdorferi OspA is modulated by the lipid modification of the antigen. AB - BACKGROUND: Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively. CONCLUSIONS/SIGNIFICANCE: Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response. PMID- 20585452 TI - Protective unfolded protein response in human pancreatic beta cells transplanted into mice. AB - BACKGROUND: There is great interest about the possible contribution of ER stress to the apoptosis of pancreatic beta cells in the diabetic state and with islet transplantation. METHODS AND FINDINGS: Expression of genes involved in ER stress were examined in beta cell enriched tissue obtained with laser capture microdissection (LCM) from frozen sections of pancreases obtained from non diabetic subjects at surgery and from human islets transplanted into ICR-SCID mice for 4 wk. Because mice have higher glucose levels than humans, the transplanted beta cells were exposed to mild hyperglycemia and the abnormal environment of the transplant site. RNA was extracted from the LCM specimens, amplified and then subjected to microarray analysis. The transplanted beta cells showed an unfolded protein response (UPR). There was activation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress, increased expression of ER chaperones and ERAD (ER-associated protein degradation) proteins. The other two arms of ER stress, PERK and ATF-6, had many down regulated genes. Downregulation of EIF2A could protect by inhibiting protein synthesis. Two genes known to contribute to apoptosis, CHOP and JNK, were downregulated. CONCLUSIONS: Human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins. PMID- 20585453 TI - Rapid microsatellite isolation from a butterfly by de novo transcriptome sequencing: performance and a comparison with AFLP-derived distances. AB - BACKGROUND: The isolation of microsatellite markers remains laborious and expensive. For some taxa, such as Lepidoptera, development of microsatellite markers has been particularly difficult, as many markers appear to be located in repetitive DNA and have nearly identical flanking regions. We attempted to circumvent this problem by bioinformatic mining of microsatellite sequences from a de novo-sequenced transcriptome of a butterfly (Euphydryas editha). PRINCIPAL FINDINGS: By searching the assembled sequence data for perfect microsatellite repeats we found 10 polymorphic loci. Although, like many expressed sequence tag derived microsatellites, our markers show strong deviations from Hardy-Weinberg equilibrium in many populations, and, in some cases, a high incidence of null alleles, we show that they nonetheless provide measures of population differentiation consistent with those obtained by amplified fragment length polymorphism analysis. Estimates of pairwise population differentiation between 23 populations were concordant between microsatellite-derived data and AFLP analysis of the same samples (r = 0.71, p<0.00001, 425 individuals from 23 populations). SIGNIFICANCE: De novo transcriptional sequencing appears to be a rapid and cost-effective tool for developing microsatellite markers for difficult genomes. PMID- 20585454 TI - The financial burden of morbidity in HIV-infected adults on antiretroviral therapy in Cote d'Ivoire. AB - BACKGROUND: Large HIV care programs frequently subsidize antiretroviral (ARV) drugs and CD4 tests, but patients must often pay for other health-related drugs and services. We estimated the financial burden of health care for households with HIV-infected adults taking antiretroviral therapy (ART) in Cote d'Ivoire. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional survey. After obtaining informed consent, we interviewed HIV-infected adults taking ART who had consecutively attended one of 18 HIV care facilities in Abidjan. We collected information on socioeconomic and medical characteristics. The main economic indicators were household capacity-to-pay (overall expenses minus food expenses), and health care expenditures. The primary outcome was the percentage of households confronted with catastrophic health expenditures (health expenditures were defined as catastrophic if they were greater than or equal to 40% of the capacity-to-pay). We recruited 1,190 adults. Median CD4 count was 187/mm(3), median time on ART was 14 months, and 72% of subjects were women. Mean household capacity-to-pay was $213.7/month, mean health expenditures were $24.3/month, and 12.3% of households faced catastrophic health expenditures. Of the health expenditures, 75.3% were for the study subject (ARV drugs and CD4 tests, 24.6%; morbidity events diagnosis and treatment, 50.1%; transportation to HIV care centres, 25.3%) and 24.7% were for other household members. When we stratified by most recent CD4 count, morbidity events related expenses were significantly lower when subjects had higher CD4 counts. CONCLUSIONS/SIGNIFICANCE: Many households in Cote d'Ivoire face catastrophic health expenditures that are not attributable to ARV drugs or routine follow-up tests. Innovative schemes should be developed to help HIV-infected patients on ART face the cost of morbidity events. PMID- 20585455 TI - How pig sperm prepares to fertilize: stable acrosome docking to the plasma membrane. AB - BACKGROUND: Mammalian sperms are activated in the oviduct. This process, which involves extensive sperm surface remodelling, is required for fertilization and can be mimicked under in vitro fertilization conditions (IVF). METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that such treatments caused stable docking and priming of the acrosome membrane to the apical sperm head surface without the emergence of exocytotic membrane fusion. The interacting membranes could be isolated as bilamellar membrane structures after cell disruption. These membrane structures as well as whole capacitated sperm contained stable ternary trans-SNARE complexes that were composed of VAMP 3 and syntaxin 1B from the plasma membrane and SNAP 23 from the acrosomal membrane. This trans-SNARE complex was not observed in control sperm. CONCLUSIONS/SIGNIFICANCE: We propose that this capacitation driven membrane docking and stability thereof is a preparative step prior to the multipoint membrane fusions characteristic for the acrosome reaction induced by sperm-zona binding. Thus, sperm can be considered a valuable model for studying exocytosis. PMID- 20585456 TI - Complete nucleotide sequence of CTX-M-15-plasmids from clinical Escherichia coli isolates: insertional events of transposons and insertion sequences. AB - BACKGROUND: CTX-M-producing Escherichia coli strains are regarded as major global pathogens. METHODOLOGY/PRINCIPAL FINDINGS: The nucleotide sequence of three plasmids (pEC_B24: 73801-bp; pEC_L8: 118525-bp and pEC_L46: 144871-bp) from Escherichia coli isolates obtained from patients with urinary tract infections and one plasmid (pEC_Bactec: 92970-bp) from an Escherichia coli strain isolated from the joint of a horse with arthritis were determined. Plasmid pEC_Bactec belongs to the IncI1 group and carries two resistance genes: bla(TEM-1) and bla(CTX-M-15). It shares more than 90% homology with a previously published bla(CTX-M)-plasmid from E. coli of human origin. Plasmid pEC_B24 belongs to the IncFII group whereas plasmids pEC_L8 and pEC_L46 represent a fusion of two replicons of type FII and FIA. On the pEC_B24 backbone, two resistance genes, bla(TEM-1) and bla(CTX-M-15), were found. Six resistance genes, bla(TEM-1), bla(CTX-M-15), bla(OXA-1), aac6'-lb-cr, tetA and catB4, were detected on the pEC_L8 backbone. The same antimicrobial drug resistance genes, with the exception of tetA, were also identified on the pEC_L46 backbone. Genome analysis of all 4 plasmids studied provides evidence of a seemingly frequent transposition event of the bla(CTX-M-15)-ISEcp1 element. This element seems to have a preferred insertion site at the tnpA gene of a bla(TEM)-carrying Tn3-like transposon, the latter itself being inserted by a transposition event. The IS26-composite transposon, which contains the bla(OXA-1), aac6'-lb-cr and catB4 genes, was inserted into plasmids pEC_L8 and pEC_L46 by homologous recombination rather than a transposition event. Results obtained for pEC_L46 indicated that IS26 also plays an important role in structural rearrangements of the plasmid backbone and seems to facilitate the mobilisation of fragments from other plasmids. CONCLUSIONS: Collectively, these data suggests that IS26 together with ISEcp1 could play a critical role in the evolution of diverse multiresistant plasmids found in clinical Enterobacteriaceae. PMID- 20585458 TI - A Lagrangian identification of the main sources of moisture affecting northeastern Brazil during its pre-rainy and rainy seasons. AB - This work examines the sources of moisture affecting the semi-arid Brazilian Northeast (NEB) during its pre-rainy and rainy season (JFMAM) through a Lagrangian diagnosis method. The FLEXPART model identifies the humidity contributions to the moisture budget over a region through the continuous computation of changes in the specific humidity along back or forward trajectories up to 10 days period. The numerical experiments were done for the period that spans between 2000 and 2004 and results were aggregated on a monthly basis. Results show that besides a minor local recycling component, the vast majority of moisture reaching NEB area is originated in the south Atlantic basin and that the nearby wet Amazon basin bears almost no impact. Moreover, although the maximum precipitation in the "Poligono das Secas" region (PS) occurs in March and the maximum precipitation associated with air parcels emanating from the South Atlantic towards PS is observed along January to March, the highest moisture contribution from this oceanic region occurs slightly later (April). A dynamical analysis suggests that the maximum precipitation observed in the PS sector does not coincide with the maximum moisture supply probably due to the combined effect of the Walker and Hadley cells in inhibiting the rising motions over the region in the months following April. PMID- 20585457 TI - The structure of tumor endothelial marker 8 (TEM8) extracellular domain and implications for its receptor function for recognizing anthrax toxin. AB - Anthrax toxin, which is released from the gram-positive bacterium Bacillus anthracis, is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds a receptor on the surface of the target cell and further assembles into a homo-heptameric pore through which EF and LF translocate into the cytosol. Two distinct cellular receptors for anthrax toxin, TEM8/ANTXR1 and CMG2/ANTXR2, have been identified, and it is known that their extracellular domains bind PA with low and high affinities, respectively. Here, we report the crystal structure of the TEM8 extracellular vWA domain at 1.7 A resolution. The overall structure has a typical integrin fold and is similar to that of the previously published CMG2 structure. In addition, using structure based mutagenesis, we demonstrate that the putative interface region of TEM8 with PA (consisting of residues 56, 57, and 154-160) is responsible for the PA-binding affinity differences between the two receptors. In particular, Leu56 was shown to be a key factor for the lower affinity of TEM8 towards PA compared with CMG2. Because of its high affinity for PA and low expression in normal tissues, an isolated extracellular vWA domain of the L56A TEM8 variant may serve as a potent antitoxin and a potential therapeutic treatment for anthrax infection. Moreover, as TEM8 is often over-expressed in tumor cells, our TEM8 crystal structure may provide new insights into how to design PA mutants that preferentially target tumor cells. PMID- 20585459 TI - Small DNA pieces in C. elegans are intermediates of DNA fragmentation during apoptosis. AB - While studying small noncoding RNA in C. elegans, we discovered that protocols used for isolation of RNA are contaminated with small DNA pieces. After electrophoresis on a denaturing gel, the DNA fragments appear as a ladder of bands, approximately 10 nucleotides apart, mimicking the pattern of nuclease digestion of DNA wrapped around a nucleosome. Here we show that the small DNA pieces are products of the DNA fragmentation that occurs during apoptosis, and correspondingly, are absent in mutant strains incapable of apoptosis. In contrast, the small DNA pieces are present in strains defective for the engulfment process of apoptosis, suggesting they are produced in the dying cell prior to engulfment. While the small DNA pieces are also present in a number of strains with mutations in predicted nucleases, they are undetectable in strains containing mutations in nuc-1, which encodes a DNase II endonuclease. We find that the small DNA pieces can be labeled with terminal deoxynucleotidyltransferase only after phosphatase treatment, as expected if they are products of DNase II cleavage, which generates a 3' phosphate. Our studies reveal a previously unknown intermediate in the process of apoptotic DNA fragmentation and thus bring us closer to defining this important pathway. PMID- 20585460 TI - Stage-specific effects of candidate heterochronic genes on variation in developmental time along an altitudinal cline of Drosophila melanogaster. AB - BACKGROUND: Previously, we have shown there is clinal variation for egg-to-adult developmental time along geographic gradients in Drosophila melanogaster. Further, we also have identified mutations in genes involved in metabolic and neurogenic pathways that affect development time (heterochronic genes). However, we do not know whether these loci affect variation in developmental time in natural populations. METHODOLOGY/PRINCIPAL FINDINGS: Here, we constructed second chromosome substitution lines from natural populations of Drosophila melanogaster from an altitudinal cline, and measured egg-adult development time for each line. We found not only a large amount of genetic variation for developmental time, but also positive associations of the development time with thermal amplitude and altitude. We performed genetic complementation tests using substitution lines with the longest and shortest developmental times and heterochronic mutations. We identified segregating variation for neurogenic and metabolic genes that largely affected the duration of the larval stages but had no impact on the timing of metamorphosis. CONCLUSIONS/SIGNIFICANCE: Altitudinal clinal variation in developmental time for natural chromosome substitution lines provides a unique opportunity to dissect the response of heterochronic genes to environmental gradients. Ontogenetic stage-specific variation in invected, mastermind, cricklet and CG14591 may affect natural variation in development time and thermal evolution. PMID- 20585462 TI - Intent to receive pandemic influenza A (H1N1) vaccine, compliance with social distancing and sources of information in NC, 2009. AB - BACKGROUND: Public adherence to influenza vaccination recommendations has been low, particularly among younger adults and children under 2, despite the availability of safe and effective seasonal vaccine. Intention to receive 2009 pandemic influenza A (H1N1) vaccine has been estimated to be 50% in select populations. This report measures knowledge of and intention to receive pandemic vaccine in a population-based setting, including target groups for seasonal and H1N1 influenza. METHODOLOGY AND PRINCIPAL FINDINGS: On August 28-29, 2009, we conducted a population-based survey in 2 counties in North Carolina. The survey used the 30x7 two-stage cluster sampling methodology to identify 210 target households. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Knowledge of pandemic influenza A (H1N1) vaccine was high, with 165 (80%) aware that a vaccine was being prepared. A total of 133 (64%) respondents intended to receive pandemic vaccine, 134 (64%) intended to receive seasonal vaccine, and 109 (53%) intended to receive both. Reporting great concern about H1N1 infection (PR 1.55; 95%CI: 1.30, 1.85), receiving seasonal influenza vaccine in 2008-09 (PR 1.47; 95%CI: 1.18, 1.82), and intending to receive seasonal influenza vaccine in 2009-10 (PR 1.27; 95%CI: 1.14, 1.42) were associated with intention to receive pandemic vaccine. Not associated were knowledge of vaccine, employment, having children under age 18, gender, race/ethnicity and age. Reasons cited for not intending to get vaccinated include not being at risk for infection, concerns about vaccine side effects and belief that illness caused by pandemic H1N1 would be mild. Forty-five percent of households with children under 18 and 65% of working adults reported ability to comply with self-isolation at home for 7-10 days if recommended by authorities. CONCLUSIONS AND SIGNIFICANCE: This is the first report of a population based rapid assessment used to assess knowledge and intent to receive pandemic vaccine in a community sample. Intention to receive pandemic and seasonal vaccines was higher than previously published reports. To reach persons not intending to receive pandemic vaccine, public health communications should focus on the perceived risk of infection and concerns about vaccine safety. PMID- 20585461 TI - Desire and dread from the nucleus accumbens: cortical glutamate and subcortical GABA differentially generate motivation and hedonic impact in the rat. AB - BACKGROUND: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. METHODOLOGY/PRINCIPAL FINDINGS: Microinjections of a GABA(A) agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic "liking" or "disliking" by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste "liking" (at rostral sites) versus "disliking" (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation. CONCLUSIONS/SIGNIFICANCE: We conclude that the nucleus accumbens contains two functional affective keyboards for amino acid signals: a motivation-generating keyboard and a hedonic-generating keyboard. Corticolimbic glutamate signals and subcortical GABA signals equivalently engage the motivation keyboard to generate desire and-or dread. Only subcortical GABA signals additionally engage the hedonic keyboard to amplify affective "liking" and "disliking" reactions. We thus suggest that top-down cortical glutamate signals powerfully regulate motivation components, but are relatively unable to penetrate core hedonic components of emotion. That may carry implications of limits to therapeutic regulation of pathological emotions. PMID- 20585463 TI - Trapped Field Characteristics of Stacked YBCO Thin Plates for Compact NMR Magnets: Spatial Field Distribution and Temporal Stability. AB - This paper presents experimental and analytical results of trapped field characteristics of a stack of square YBCO thin film plates for compact NMR magnets. Each YBCO plate, 40 mm * 40 mm * 0.08 mm, has a 25-mm diameter hole at its center. A total of 500 stacked plates were used to build a 40-mm long magnet. Its trapped field, in a bath of liquid nitrogen, was measured for spatial field distribution and temporal stability. Comparison of measured and analytical results is presented: the effects on trapped field characteristics of the unsaturated nickel substrate and the non-uniform current distribution in the YBCO plate are discussed. PMID- 20585464 TI - Animal Modeling and Neurocircuitry of Dual Diagnosis. AB - Dual diagnosis is a problem of tremendous depth and scope, spanning many classes of mental disorders and addictive drugs. Animal models of psychiatric disorders studied in addiction paradigms suggest a unitary nature of mental illness and addiction vulnerability both on the neurocircuit and clinical-behavioral levels. These models provide platforms for exploring the interactive roles of biological, environmental and developmental factors on neurocircuits commonly involved in psychiatric and addiction diseases. While suggestive of the artifice of segregated research, training, and clinical cultures between psychiatric and addiction fields, this research may lead to more parsimonious, integrative and preventative treatments for dual diagnosis. PMID- 20585465 TI - Institutionalized ghosting: policy contexts and language use in erasing the person with Alzheimer's. AB - The ordinary social engagement of human life would not usually be considered an arena for language policy. Yet clinical evidence mounts that social interaction improves our lives as we age. Since social engagement decreases cardiovascular risks (Ramsay et al. in Ann Epidemiol 18:476-483, 2008) and delays memory loss among those living in communities (Ertel et al. in Am J Public Health 98:1215 1220, 2008), practices that prohibit social interaction threaten human well being. For persons who have Alzheimer's disease (AD), social interaction continues to play an integral part in cognitive function and delays in memory loss, according to a longitudinal study of social networks (Bennett et al. in Lancet Neurol 5:406-412, 2007). Increasingly, person-centered care that promotes social engagement for those with AD is promoted as an institutional policy to improve outcomes of dementia care (Edvardsson et al. in Int Psychogeriatr 20:764 776, 2008). Yet the training of caregivers may neither reflect person-centered care nor include attention to communication, suggesting covert policies in practice. PMID- 20585466 TI - Filtered Backprojection Reconstruction with Depth-Dependent Filtering. AB - A direct filtered-backprojection (FBP) reconstruction algorithm is presented for circular cone-beam computed tomography (CB-CT) that allows the filter operation to be applied efficiently with shift-variant band-pass characteristics on the kernel function. Our algorithm is derived from the ramp-filter based FBP method of Feldkamp et al. and obtained by decomposing the ramp filtering into a convolution involving the Hilbert kernel (global operation) and a subsequent differentiation operation (local operation). The differentiation is implemented as a finite difference of two (Hilbert filtered) data samples and carried out as part of the backprojection step. The spacing between the two samples, which defines the low-pass characteristics of the filter operation, can thus be selected individually for each point in the image volume. We here define the sample spacing to follow the magnification of the divergent-beam geometry and thus obtain a novel, depth-dependent filtering algorithm for circular CB-CT. We evaluate this resulting algorithm using computer-simulated CB data and demonstrate that our algorithm yields results where spatial resolution and image noise are distributed much more uniformly over the field-of-view, compared to Feldkamp's approach. PMID- 20585467 TI - The Catalytic Asymmetric Intramolecular Stetter Reaction. AB - This account chronicles our efforts at the development of a catalytic asymmetric Stetter reaction using chiral triazolium salts as small molecule organic catalysts. Advances in the mechanistically related azolium-catalyzed asymmetric benzoin reaction are discussed, particularly as they apply to catalyst design. A chronological treatise of reaction discovery, catalyst optimization and reactivity extension follows. PMID- 20585468 TI - Evidence-Based Practices for Parentally Bereaved Children and Their Families. AB - Parental death is one of the most traumatic events that can occur in childhood, and several reviews of the literature have found that the death of a parent places children at risk for a number of negative outcomes. This article describes the knowledge base regarding both empirically-supported, malleable factors that have been shown to contribute to or protect children from mental health problems following the death of a parent and evidence-based practices to change these factors. In addition, nonmealleable factors clinicians should consider when providing services for children who have experienced the death of a parent are reviewed. PMID- 20585469 TI - Examining How Context Changes Intervention Impact: The Use of Effect Sizes in Multilevel Mixture Meta-Analysis. AB - In describing the impact of an intervention, a single effect size, odds ratio, or other summary measure is often employed. This single measure is useful in calibrating the effect of one intervention against others, but it is less meaningful when the intervention displays variation in impact. A single intervention trial can show differential effects when subgroups respond differentially, when impact varies by environmental context, or when there is varying impact with different outcome measures or across follow-up time. This article presents a multilevel mixture modeling approach for meta-analyses that summarizes these sources of impact variation across trials and measured outcomes. PMID- 20585471 TI - Nanoparticle technology: Addressing the fundamental roadblocks to protein biomarker discovery. AB - The incorporation of affinity baits into N-isopropylacrylamide-hydrogel-based nanoparticles offers a novel technology that addresses the major analytical challenges of disease biomarker discovery. In solution in complex biologic fluids (e.g. blood or urine), core-shell bait-containing nanoparticles can perform three functions in one step: (a) sieve molecules according to size, (b) sequestrate and concentrate target analytes, and (c) protect analytes from degradation. PMID- 20585470 TI - Alterations in striatal synaptic transmission are consistent across genetic mouse models of Huntington's disease. AB - Since the identification of the gene responsible for HD (Huntington's disease), many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI (knock-in) mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons) in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition. PMID- 20585472 TI - Omics.pnl.gov: A Portal for the Distribution and Sharing of Multi-Disciplinary Pan-Omics Information. PMID- 20585473 TI - Growth and Landscape Performance of Ten Herbaceous Species in Response to Saline Water Irrigation. AB - Ten herbaceous perennials and groundcovers were grown in raised beds from June to September in a dry, hot desert environment and micro-spray drip irrigated with synthesized saline solutions at electrical conductivity of 0.8 (tap water), 3.2, or 5.4 dS/m. Plant height and two perpendicular widths were recorded monthly to calculate the growth index. Landscape performance was assessed monthly by visual scores. Salinity did not affect the visual scores in Achillea millefolium L., Gaillardia aristata Pursh, Lantana x hybrida 'New Gold', Lonicera japonica Thunb. 'Halliana', and Rosmarinus officinalis L. 'Huntington Carpet' throughout the experiment. Glandularia canadensis (L.) Nutt. 'Homestead Purple' performed better than Glandularia x hybrida (Gronland & Rumpler) G. L. Nesom & Pruski. Lantana montevidensis (Spreng.) Brig. had lower visual scores at 5.4 dS/m compared to the control and 3.2 dS/m. Most plants of Rudbeckia hirta L. did not survive when irrigated at 3.2 dS/m or 5.4 dS/m. Shoot biomass of A. millefolium, G. aristata, L. x hybrida, L. japonica, R. officinalis, and V. macdougalii was not influenced by the salinity of irrigation water. Therefore, A. millefolium, G. aristata, L. x hybrida, L. japonica, and R. officinalis can be irrigated with non-potable water at salinity up to 5.4 dS/m with little reduction in growth and aesthetic appearance. PMID- 20585475 TI - Simple diagnostic tests for subungual pigmentation. AB - Subungual pigmentation can have benign and malignant etiologies. A common and important differential diagnosis is between subungual hematoma and subungual acrolentiginous melanoma. We have introduced Dr. Eckert Haneke's technique and our Hydrogen Peroxide modification for distinguishing these entities clinically. Dr. Haneke's technique uses the hemocult reaction to detect hematoma from the specimen, while our modification uses Hydrogen Peroxide to clear the hematoma and make the decision clinically. Both are minimally invasive techniques which can be performed without pain. Often these procedures spare the patient an unnecessary tissue biopsy with its morbidity and discomfort. Importantly, they reassure the patient that he or she has a benign disorder. PMID- 20585474 TI - Brain stimulation for the treatment of pain: A review of costs, clinical effects, and mechanisms of treatment for three different central neuromodulatory approaches. AB - Methods of cortical stimulation including epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) are emerging as alternatives in the management of pain in patients with chronic medically-refractory pain disorders. Here we consider the three methods of brain stimulation that have been investigated for the treatment of central pain: MCS, rTMS, and tDCS. While all three treatment modalities appear to induce significant clinical gains in patients with chronic pain, tDCS is revealed as the most cost-effective approach (compared to rTMS and MCS) when considering a single year of treatment. However, if a 5-year treatment is considered, MCS is revealed as the most cost-effective modality (as compared to rTMS and tDCS) for the neuromodulatory treatment of chronic pain. We discuss the theory behind the application of each modality as well as efficacy, cost, safety, and practical considerations. PMID- 20585477 TI - Determining the severity of atopic dermatitis in children presenting in general practice: an easy and fast method. AB - Assessment of the severity of atopic dermatitis (AD) is necessary to evaluate the disease process. This study evaluates and validates the TIS in children with AD presenting in general practice. Independent investigators determined the severity of AD using the TIS and the objective SCORAD. The interobserver agreement for the TIS and SCORAD was calculated, as was the correlation between TIS and SCORAD. The mean time to assess the TIS was less than one minute. A moderate-to-good agreement between the observers was found for the TIS (kappa = 0.604 or 0.464), or SCORAD (kappa = 0.695 or 0.700). There was an excellent correlation between TIS and SCORAD (r(s) = 0.755-0.839). In conclusion, the TIS is an easy and fast method to score AD. Because of the moderate to good interobserver agreement and the high correlation with the SCORAD, we recommend the TIS to determine the severity of AD in general practice. PMID- 20585476 TI - Diagnostic pitfalls in newborns and babies with blisters and erosions. AB - Establishing the correct diagnosis in newborns presenting with blisters and erosions is not always a straightforward process. Many different disease entities including acquired (i.e., infectious, immunobullous, traumatic) and inherited disorders have to be taken into consideration. Similarities in clinical appearance, colonization and/or superinfections of preexisting skin lesions, as well as the absence of late changes in the neonate often pose significant diagnostic challenges. In this paper we discuss by giving examples the process of making an accurate diagnosis of blistering skin diseases in the neonatal period on the basis of a diagnostic algorithm. In addition, we provide an overview of the rational use and the limitations of laboratory procedures such as microbial testing, routine light microscopy, immunofluorescence antigen mapping, transmission electron microscopy, and molecular genetic analysis. PMID- 20585478 TI - Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Takayasu's Arteritis. AB - Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20-30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasu's arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG. PMID- 20585479 TI - Clinical characteristics of cutaneous melanoma and second primary malignancies in a dutch hospital-based cohort of cutaneous melanoma patients. AB - The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy. In conclusion, 48 patients developed a subsequent malignancy. As nonmelanoma skin cancer is the most frequent second malignancy, our results subscribe to the necessity of follow-up by a dermatologist. PMID- 20585480 TI - An experimental in vivo model to characterize "heavy legs" symptom in topical formulations. AB - The "Heavy legs" symptom is regarded as an early expression of chronic venous failure, estimated to affect 40% of the population in developing countries. A new methodology is proposed to approach the "tired or heavy legs" symptom. Seven females with this complaint applied a standard topical formulation during 28 days in one leg randomly chosen. Local blood flow records were obtained instantaneously and during postural change with a laser doppler flowmeter (LDF). High-frequency sonography and local morphometry were also obtained at Days 0, 14, and 28. When compared with D0, LDF values present a significant decrease of both basal and dynamical values after Day 14 and Day 28 suggesting that this effect may result from the formulation application, also involving the related massage. Centimetric measurements and sonographic analysis also supported those inferences. The proposed methodology can evaluate the dynamical changes of "heavy legs" symptom and eventually be very useful to assess the related claim support. PMID- 20585481 TI - Progressive macular hypomelanosis: a rarely diagnosed hypopigmentation in Caucasians. AB - A 35-year-old woman who developed whitish macules on trunk and limbs at 12 years of age and observed a remarkable increase of the hypopigmentated lesions after her pregnancies at ages 29 and 32 years. Because of the highly characteristic clinical aspect and the light- and electron-microscopic histopathologic findings, we diagnosed progressive macular hypomelanosis (PMH). It is a nonscaly disorder with hypopigmented macules mainly on the trunk and is more often seen in young women. In contrast to some authors assuming the presence of Propionibacterium spp. as a matter of principle in PMH, we report a case with no evidence for Propionibacterium spp. PMID- 20585483 TI - Desmoplastic melanoma: report of 5 cases. AB - Background. The clinical presentation of desmoplastic melanoma is often challenging. We report the experience of the Melanoma Unit of Spedali Civili University Hospital of Brescia, Italy. Method. Study subjects were drawn from 1770 patients with histologica confirmed melanoma. Within this group, desmoplastic melanoma developed in 5 patients. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated. Results. Of the 5 patients described in this study, 2 were males and 3 females. The average age was 62.4 years ranging from 56 to 68 years. Breslow thickness ranged from 2.1 to 12 mm with a mean thickness of 5.8 mm. Primary treatment of 5 patients included a wide local excision of their primary lesions. Conclusions. Desmoplastic melanoma is a rare neoplasm which clinically may mimic other tumours or cutaneous infiltrate of uncertain significance. The diagnosis is hiastopathological and radical resection is necessary. PMID- 20585482 TI - Cutaneous scarring: a clinical review. AB - Cutaneous scarring can cause patients symptoms ranging from the psychological to physical pain. Although the process of normal scarring is well described the ultimate cause of pathological scarring remains unknown. Similarly, exactly how early gestation fetuses can heal scarlessly remains unsolved. These questions are crucial in the search for a preventative or curative antiscarring agent. Such a discovery would be of enormous medical and commercial importance, not least because it may have application in other tissues. In the clinical context the assessment of scars is becoming more sophisticated and new physical, medical and surgical therapies are being introduced. This review aims to summarise some of the recent developments in scarring research for non-specialists and specialists alike. PMID- 20585484 TI - Response of fibroblastic rheumatism to infliximab. AB - Onset is usually sudden with symmetrical articular involvement of both small and large joints, occurrence of solid skin nodules, and rapid progression. Treatment is generally unrewarding. Here we report a severe and disabling case of FR responding favorably to infliximab therapy. After 32 weeks of continuous treatment, skin lesions dramatically improved and arthropathy partially regressed. PMID- 20585485 TI - Looking back.......looking ahead. PMID- 20585486 TI - The basket trainer: A homemade laparoscopic trainer attainable to every resident. AB - Laparoscopic trainers have been proved to be effective to improve skills of laparoscopic surgery; they are usually installed at hospital in the surgical department with limited access hours, usually inconvenient to the schedule of the resident. Simple trainer boxes are necessary for residents who desire developing their skills at home independently to the venue and hours of surgical departments. Our goal is to bring the laparoscopic trainer to the desktop of the surgical resident by making it very cheap, small, light, secure and easy to construct. We describe a model of laparoscopic trainer using steel basket which, we believe, meets all of the above-mentioned requirements. It is accessible to any personal budget and can be constructed with a minimum of hand skill. It is small and light enough to permit its daily use on the desktop of the resident for a couple of hours, then after it can be stocked in any locker. PMID- 20585487 TI - Anastomotic leak rate and outcome for laparoscopic intra-corporeal stapled anastomosis. AB - AIMS: A prospective clinical audit of all patients undergoing laparoscopic surgery with the intention of primary colonic left-sided intracorporeal stapled anastomosis to identify the rate of anastomotic leaks on an intention to treat basis with or without defunctioning stoma. MATERIALS AND METHODS: All patients undergoing laparoscopic colorectal surgery resulting in left-sided stapled anastomosis were included with no selection criteria applied. All operations were conducted by the same surgical team and the same preparation and intraoperative methods were used. The factors analyzed for this audit were patient demographics (age and sex), indication for operation, procedure performed, height of anastomosis, leak rate and the outcome, inpatient stay, mortality, rate of defunctioning stomas, and rate of conversion to open procedure. Results for anastomotic leakage were compared with known results from the Wessex Colorectal Audit for open colorectal surgery. RESULTS: A total of 69 patients (43 females, 26 males; median age 69 years, range 19 - 86 years) underwent colonic procedures with left-sided intracorporeal stapled anastomoses. Of these, 14 patients underwent reversal of Hartmann's, 42 - Anterior Resection, 11 - Sigmoid Colectomy, 2 - Left Hemicolectomy. Excluding reversals of Hartmann's, 29 operations were performed for malignant and 26 for benign disease. Five patients were defunctioned, and 3 were subsequently reversed. The median height of anastomosis was 12 cm, range 4 - 18 cm from anal verge as measured either intra operatively, or by rigid sigmoidoscopy post-operatively. Four cases were converted to open surgery. There was 1 post-operative death within 30 days. There was 1 anastomotic leak (the patient that died), and 1 patient developed a colo vesical fistula. Median post-operative stay was 7 days, range 2-19. CONCLUSION: This clinical audit confirms that the anastomotic leak rate for left-sided colorectal stapled anastomosis is no worse than that for open surgery. Therefore the decision making process for defunctioning stoma should be guided by the same principles as open surgery. PMID- 20585488 TI - One stage bilateral endoscopic sympathectomy under local anesthesia: Is a valid, and safe procedure for treatment of palmer hyperhidrosis? AB - OBJECTIVE: Thoracoscopic sympathetic surgery is currently the best treatment for hyperhidrosis, and the success rate is quite high, but poor emphasis has been given to the type of anaesthesia and its application through either one or two stages of surgery. This study has evaluated the operative and postoperative results of one-stage bilateral thoracoscopic sympathectomy under local anaesthesia. MATERIALS AND METHODS: From 2003 to 2007, n=14 patients with hyperhidrosis of the upper limbs [4 females and 10 males] with a mean age of 28+/ 2.11 year [range 26-44] were included. They were operated on by means of bilateral ETS under local anaesthesia. The mean follow-up was 1.5 years (range 13 24 months). RESULTS: No operative mortality was recorded. The mean operating room time for the whole bilateral procedure under was 73. 5+/-14.5 range [60 -120] min most of the patients were discharged the same day after a chest roentgenogram except, only two patients with gustatory sweating one recurrent sweating in the patient who had previously axillary hyperhidrosis. Also among them two patients (20%) experienced a minimal pneumothorax that required no treatment. Postoperative quality of life and satisfaction were excellent and cost was significantly reduced. CONCLUSIONS: Bilateral thoracoscopic sympathectomy for palmar hyperhidrosis could be safely and effectively performed in patients refusing GA regarding cost and satisfaction. PMID- 20585489 TI - Systemic inflammatory response syndrome following laparoscopic repair of diaphragmatic injury: A case report. AB - Trauma is a major cause of morbidity and mortality in the younger age group. Though diagnostic laparoscopy has been attempted in trauma earlier, with the advance in minimal access techniques, there is an increasing attempt at advancing the indications for laparoscopy in the setting of trauma. Though there are reports and studies on the successful use of laparoscopy in the setting of abdominal trauma, it is essential to remember that laparoscopy in trauma is associated with risks inherent in the procedure itself and also with higher incidence of missed injuries if used as a diagnostic tool. PMID- 20585490 TI - Laparoscopic appendicectomy for suspected mesh-induced appendicitis after laparoscopic transabdominal preperitoneal polypropylene mesh inguinal herniorraphy. AB - Laparoscopic inguinal herniorraphy via a transabdominal preperitoneal (TAPP) approach using Polypropylene Mesh (Mesh) and staples is an accepted technique. Mesh induces a localised inflammatory response that may extend to, and involve, adjacent abdominal and pelvic viscera such as the appendix. We present an interesting case of suspected Mesh-induced appendicitis treated successfully with laparoscopic appendicectomy, without Mesh removal, in an elderly gentleman who presented with symptoms and signs of acute appendicitis 18 months after laparoscopic inguinal hernia repair. Possible mechanisms for Mesh-induced appendicitis are briefly discussed. PMID- 20585491 TI - Port site closure after laparoscopic surgery. AB - We have reported a novel technique for the closure of the ports after laparoscopic surgery. Using this technique all the ports are closed under vision, thus preventing port herniation. PMID- 20585492 TI - Laparoscopic feeding jejunostomy. PMID- 20585493 TI - Laparoscopic removal of worm in biliary canal. PMID- 20585494 TI - Rescue behavior: Distinguishing between rescue, cooperation and other forms of altruistic behavior. AB - Reports of rescue behavior in non-human animals are exceedingly rare, except in ants where rescue is well known, but has not been explored experimentally until recently. Although we predict that rescue behavior should be limited to circumstances in which the victim and the rescuer are highly related to one another, or in which unrelated individuals must cooperate very closely with one another, we also predict that it is likely to be far more common than the current literature would suggest. To address this oversight, we propose a rigorous definition of rescue behavior, one that helps researchers to focus on its necessary and sufficient components, at the same time that it helps to differentiate rescue behavior from cooperation and other forms of helping behavior. In this way we also hope to expand our understanding of altruism in particular and kin selection in general. PMID- 20585495 TI - Bacterial effectors target BAK1-associated receptor complexes: One stone two birds. AB - The long-standing association between hosts and microbes has generated some of most intricate relationships. The studies on molecular mechanisms of host-microbe interaction have been revealing many fascinating stories. Here we zoom in on a specific topic on the interplay between bacterial effectors and plant innate immune signaling. In particular, we will summarize our recent discovery that bacterial effector proteins, AvrPto and AvrPtoB, target plant immune signaling receptor complexes to interfere with host immune responses and development. PMID- 20585496 TI - A fine control of quorum-sensing communication in Agrobacterium tumefaciens. AB - The bacterial pathogen Agrobacterium tumefaciens produces the quorum-sensing (QS) signal 3-oxo-octanoylhomoserine lactone (OC8HSL) for controlling horizontal transfer of its tumor inducing (Ti) plasmid that carries both the T-DNA and the virulence genes. Over-accumulation of OC8HSL also increases severity of plant symptoms (number of emerging tumors at infection site) by an unknown mechanism. A. tumefaciens strain C58 expresses two lactonases, AttM (BlcC) and AiiB, that cleave OC8HSL and are potential modulators of QS. Recent data highlight the direct contribution of lactonases AttM and AiiB in the control of OC8HSL level and QS-regulated functions such as conjugation of Ti plasmid and seriousness of plant symptoms. Expression of the two lactonases is regulated by different plant signals. A working model of QS in the course of the A. tumefaciens-plant host interaction is proposed and discussed. PMID- 20585497 TI - The F-BAR protein family Actin' on the membrane. AB - A tight spatio-temporal coordination of the machineries controlling actin dynamics and membrane remodelling is crucial for a huge variety of cellular processes that shape cells into a multicellular organism. Dynamic membrane remodelling is achieved by a functional relationship between proteins that control plasma membrane curvature, membrane fission and nucleation of new actin filaments. The BAR/F-BAR-domain-containing proteins are prime candidates to couple plasma membrane curvature and actin dynamics in different morphogenetic processes. Here, we discuss recent findings on the membrane-shaping proteins of the F-BAR domain subfamily and how they regulate morphogenetic processes in vivo. PMID- 20585498 TI - Reward expectations in honeybees. AB - The study of expectations of reward helps to understand rules controlling goal directed behavior as well as decision making and planning. I shall review a series of recent studies focusing on how the food gathering behavior of honeybees depends upon reward expectations. These studies document that free-flying honeybees develop long-term expectations of reward and use them to regulate their investment of energy/time during foraging. Also, they present a laboratory procedure suitable for analysis of neural substrates of reward expectations in the honeybee brain. I discuss these findings in the context of individual and collective foraging, on the one hand, and neurobiology of learning and memory of reward. PMID- 20585499 TI - Regulation of WASp by phosphorylation: Activation or other functions? AB - Wiskott-Aldrich Syndrome protein (WASp) is an actin nucleation-promoting factor that regulates actin polymerisation via the Arp2/3 complex. Its mutation in human syndromes has led to extensive studies on the regulation and activities of this molecule. Several mechanisms for the regulation of WASp activity have been proposed, however, the role of tyrosine phosphorylation remains controversial, particularly due to inconsistencies between results obtained through biochemical and cell biological approaches. In this mini-review, we are addressing the major aspects of WASp regulation with an emphasis on the role of tyrosine phosphorylation on WASp activities. PMID- 20585500 TI - The regulation of synaptic function by alpha-synuclein. AB - The cytosolic protein alpha-synuclein is enriched at the pre-synaptic terminals of almost all types of neurons in the central nervous system. alpha-Synuclein overexpression and the expression of three different mutants have been shown to sustain the pathogenesis of selected forms of Parkinson's disease. The localization of the protein and the defects found in knocked out or transgenic animals suggest a role of alpha-synuclein in the regulation of synaptic efficiency. However, the precise function of the protein and the molecular mechanisms of its action are still unclear. At synapses the synaptic vesicle release cycle is a finely tuned process composed of sequential steps that require the interconnected participation of several proteins and cytoskeletal elements. Actin microfilaments are required for the regulation of synaptic vesicle mobilization between different functional pools, for their organization at the active zone and influence the exocytotic process. We recently identified actin as a possible target of alpha-synuclein function. Through its binding to actin and the regulation of actin dynamics, alpha-synuclein could participate in the tuning of the vesicle release process, thereby modulating synaptic function and plasticity. PMID- 20585501 TI - Sex and stripping: The key to the intimate relationship between Wolbachia and host? AB - Wolbachia pipientis is known to infect only arthropods and nematodes (mainly filarial worms). A unique feature shared by the two Phyla is the ability to replace the exoskeleton, a process known as ecdysis. This shared characteristic is thought to reflect a common ancestry. Arthropod moulting is induced by the steroid hormone 20-hydroxyecdysone (20E) and a role for ecdysteroids in nematode ecdysis has also been suggested. Removing Wolbachia from filarial worms impairs the host's development. From analyses of the genome of Wolbachia harbored by the filarial nematode Brugia malayi and that of its host, the bacterium may provide a source of heme, an essential component of cytochrome P450's that are necessary for steroid hormone biosynthetic pathways.In arthropods, Wolbachia is a reproductive manipulator, inducing various phenotypic effects that may be due to differences in host physiology, in particular, endocrine-related processes governing development and reproduction. Insect steroids have well-defined roles in the coordination of multiple developmental processes, and in adults they control important aspects of reproduction, including ovarian development, oogenesis, sexual behavior, and in some taxa vitellogenin biosynthesis.According to some authors ecdysteroids may also act as sex hormones. In insects sex differentiation is generally thought to be a strictly genetic process, in which each cell decides its own sexual fate based on its sex chromosome constitution, but, surprisingly, recent data demonstrate that in Drosophila sex determination is not cell-autonomous, as it happens in mammals. Thus the presence of signals coordinating the development of a gender-specific phenotype cannot be excluded.This could explain why Wolbachia interferes with insect reproduction; and also could explain why Wolbachia interferes with insect development.Thus, is "sex (=reproduction) and stripping (=ecdysis)" the key to the intimate relationship between Wolbachia and its host? PMID- 20585502 TI - F-BAR domain proteins: Families and function. AB - The F-BAR domain is emerging as an important player in membrane remodeling pathways. F-BAR domain proteins couple membrane remodeling with actin dynamics associated with endocytic pathways and filopodium formation. Here, we provide a comprehensive analysis of F-BAR domain proteins in terms of their evolutionary relationships and protein function. F-BAR domain containing proteins can be categorized into five subfamilies based on their phylogeny which is consistent with the additional protein domains they possess, for example, RhoGAP domains, Cdc42 binding sites, SH3 domains and tyrosine kinase domains. We derive a protein protein interaction network suggesting that dynamin1/2, N-WASP, Huntingtin, intersectin and Cdc42 are central nodes influencing F-BAR domain protein function. PMID- 20585504 TI - The rhizobacterial elicitor acetoin induces systemic resistance in Arabidopsis thaliana. AB - The majority of plant growth promoting rhizobacteria (PGPR) confer plant immunity against a wide range of foliar diseases by activating plant defences that reduce a plant's susceptibility to pathogen attack. Here we show that Arabidopsis thaliana (Col-0) plants exposed to Bacillus subtilis strain FB17 (hereafter FB17), results in reduced disease severity against Pseudomonas syringae pv. tomato DC3000 (hereafter DC3000) compared to plants without FB17 treatment. Exogenous application of the B. subtilis derived elicitor, acetoin (3-hydroxy-2 butanone), was found to trigger induced systemic resistance (ISR) and protect plants against DC3000 pathogenesis. Moreover, B. subtilis acetoin biosynthetic mutants that emitted reduced levels of acetoin conferred reduced protection to A. thaliana against pathogen infection. Further analysis using FB17 and defense compromised mutants of A. thaliana indicated that resistance to DC3000 occurs via NPR1 and requires salicylic acid (SA)/ethylene (ET) whereas jasmonic acid (JA) is not essential. This study provides new insight into the role of rhizo-bacterial volatile components as elicitors of defense responses in plants. PMID- 20585503 TI - Solute transporters in plant thylakoid membranes: Key players during photosynthesis and light stress. AB - Plants utilize sunlight to drive photosynthetic energy conversion in the chloroplast thylakoid membrane. Here are located four major photosynthetic complexes, about which we have great knowledge in terms of structure and function. However, much less we know about auxiliary proteins, such as transporters, ensuring an optimum function and turnover of these complexes. The most prominent thylakoid transporter is the proton-translocating ATP-synthase. Recently, four additional transporters have been identified in the thylakoid membrane of Arabidopsis thaliana, namely one copper-transporting P-ATPase, one chloride channel, one phosphate transporter, and one ATP/ADP carrier. Here, we review the current knowledge on the function and physiological role of these transporters during photosynthesis and light stress in plants. Subsequently, we make a survey on the outlook of thylakoid activities awaiting identification of responsible proteins. Such knowledge is necessary to understand the thylakoid network of transporters, and to design strategies for bioengineering crop plants in the future. PMID- 20585505 TI - Why sexually deceptive orchids have colored flowers. AB - Sexually deceptive orchids provide no reward to their pollinators. Instead, they mimic the sex pheromone of receptive insect females to attract males which pollinate the flowers in mating attempts. Nearly all species of the Mediterranean orchid genus Ophrys are sexually deceptive and pollinated by solitary bees and wasps. Due to the use of a highly specific olfactory communication channel most Ophrys species have, in contrast to food deceptive or rewarding orchids, an inconspicuous greenish perianth and a dark brownish labellum. However, some species possess a bright pink or white perianth, and the functional significant of such color signals in the orchid-pollinator communication system is unknown. We recently showed that the pink perianth of Ophrys heldreichii increases the performance of its bee pollinator, males of the long-horned bee Eucera (Tetralonia) berlandi, to detect the flower at short-range. At great distances (>30 cm) from the flower, male search behavior was found to be olfactory guided and unaffected by the spectral property of the perianth, i.e., chromatic and green receptor-specific contrast. However, in the near vicinity of the flower (<30 cm), where spatial vision is sufficient to detect the flower, search time only correlated with the green receptor-specific contrast between the perianth and the background. PMID- 20585506 TI - The biology of psychology: 'Simple' conditioning? AB - Operant (instrumental) and classical (Pavlovian) conditioning are taught as the simplest forms of associative learning. Recent research in several invertebrate model systems has now accumulated evidence that the dichotomy is not as simple as it seemed. During operant learning in the fruit fly Drosophila, at least two genetically distinct learning systems interact dynamically. Inspired by analogous results in three other research fields, we propose to term one of these systems world-learning (assigning value to sensory stimuli) and the other self-learning (assigning value to a specific action or movement). During the goal-directed phase of operant learning, world-learning inhibits self-learning (in Drosophila via the mushroom-body neuropil), to allow for flexible generalization. Extended training overcomes this inhibition in a phase transition akin to habit formation in vertebrates, allowing self-learning to transform spontaneous actions to habitual responses. In part, these insights were achieved by reducing operant experiments beyond the traditional set-ups (i.e., 'pure' operant learning) and using modern, molecular and/or genetic model systems. PMID- 20585507 TI - Digital kinases: A cell model for sensing, integrating and making choices. AB - Protein kinases mediate most of the signal transduction in eukaryotic cells, controlling important cellular processes. Functioning as sensors and switches, kinases play a critical role in the regulation of cell fate decisions: proliferation, differentiation or death. Cellular sensors must have signaling properties well suited for the processing and propagation of external or internal stimuli that promote irreversible processes. These properties include ultrasensitivity, hysteresis and digital responses. Ultrasensitivity means to produce a very large response to a small increase in stimulus after a threshold is crossed, hysteresis (a form of biochemical memory) means sustained activation when the stimulus has disappeared, and digital is an all-ornone response at a single cell level. These properties are present in JNK, a stress protein kinase that regulates cell death. In a recent article, we have characterized Xenopus AMPK, a stress protein kinase that controls energy levels in the cell, showing that is regulated similar to the mammalian ortholog. By using Xenopus oocytes we studied the AMPK signaling system and compared to JNK. Our work showed that AMPK is ultrasensitive to an apoptotic stimulus (hyperosmolar sorbitol) but, in contrast to JNK, does not show hysteresis. By single cell analysis we found that the response of AMPK and JNK to hyperosmolar sorbitol is all-or-none (digital) in character, and that initial graded responses of both protein kinases are converted into digital during the critical period of cytochrome c release. We proposed a model to explain the cell death program as integration of multiple digital signals from stress sensors, that now I extend to a more general model for sensing, integrating and making choices in the cell and the organism. PMID- 20585508 TI - Independence and interdependence of the photoregulation of pigmentation and development in Fremyella diplosiphon. AB - Many photosynthetic organisms exhibit light-dependent regulation of growth and development, including photoregulation of pigmentation, physiology, and form. We recently demonstrated that the photoregulation of cellular and filament morphology in Fremyella diplosiphon is under control of a photosensory photoreceptor and differentially impacted by photosynthetic pigment accumulation. Biliprotein photoreceptor RcaE controls the light-dependent regulation of pigmentation and of cell and filament morphology in F. diplosiphon, primarily in response to green and red light as a part of a light acclimation process known as complementary chromatic adaptation (CCA). Our recent investigations into the regulation of CCA underscored the largely independent regulation of pigmentation and cell shape by RcaE. However, recent studies on the regulation of phycobiliprotein biosynthesis indicated that filament length may depend upon correct photoregulation of photosynthetic pigment levels. Taken together, these studies suggest that aspects of the regulation of morphology in F. diplosiphon are independent of the regulation of pigmentation, yet other features of morphology depend upon the accurate photoregulation of pigment levels. PMID- 20585509 TI - KLHDC8B in Hodgkin lymphoma and possibly twinning. AB - A key feature of Hodgkin lymphoma is that the malignant cells are binucleated, as a consequence of failed cytokinesis. We recently ascertained a family in which multiple cases of Hodgkin lymphoma had occurred among individuals who inherited a balanced chromosomal translocation. We cloned the translocation breakpoints and found that it disrupted a previously uncharacterized gene, KLHDC8B, encoding a Kelch family protein whose deficiency impairs cytokinesis and leads to binucleated cells. In other families we found a rare single nucleotide polymorphism affecting mitotic translation of KLHDC8B that was associated with and linked to Hodgkin lymphoma. Interestingly, the index family demonstrated an unusual frequency of twins, and there is a previously reported association between Hodgkin lymphoma and twins. Here we review the unusual genetic features of Hodgkin lymphoma, including gender concordance among siblings, and genetically test the hypothesis that KLHDC8B may participate in twinning by disrupting cytokinesis through impediment of polar body separation from oocytes. PMID- 20585510 TI - Why cultural and genetic group selection are unequal partners in the evolution of human behavior. PMID- 20585511 TI - Vipp1 and PspA: Related but not twins. AB - The Vesicle Inducing Protein in Plastids 1 (Vipp1) was suggested to be involved in thylakoid membrane formation in both chloroplasts and cyanobacteria. The protein shows sequence homology to the Phage Shock Protein A (PspA) from bacteria, and both proteins have similar secondary structures. 2D-structures of PspA and of Vipp1 have been determined by electron microscopy in the recent years. Both PspA and Vipp1 form large homooligomeric rings with high molecular masses but their ring dimensions differ significantly. Furthermore, Vipp1 forms rings with different rotational symmetries whereas PspA appears to form rings with singular rotational symmetry. In this article addendum we compare the structures of PspA and Vipp1. Furthermore, we suggest a spatial structural model of the observed Vipp1 rings. PMID- 20585513 TI - Corruption of ant acoustical signals by mimetic social parasites: Maculinea butterflies achieve elevated status in host societies by mimicking the acoustics of queen ants. AB - Recent recordings of the stridulations of Myrmica ants revealed that their queens made distinctive sounds from their workers, although the acoustics of queens and workers, respectively, were the same in different species of Myrmica. Queen recordings induced enhanced protective behavior when played to workers in the one species tested. Larvae and pupae of the butterfly genus Maculinea inhabit Myrmica colonies as social parasites, and both stages generate sounds that mimic those of a Myrmica queen, inducing similar superior treatments from workers as their model. We discuss how initial penetration and acceptance as a colony member is achieved by Maculinea through mimicking the species-specific semio-chemicals of their hosts, and how acoustical mimicry is then employed to elevate the parasite's membership of that society towards the highest attainable level in their host's hierarchy. We postulate that, if acoustics is as well developed a means of communication in certain ants as these studies suggest, then others among an estimated 10,000 species of ant social parasite may supplement their well-known use of chemical and tactile mimicry to trick host ants with mimicry of host acoustical systems. PMID- 20585512 TI - Does a physiological role for KCNE subunits exist in the immune system? AB - The study of channel modulation by regulatory subunits has attracted considerable attention. Evidence indicates a pivotal role for accessory proteins in the channelosome. For instance, these regulatory subunits are necessary to recapitulate in vivo ion currents and to further understand the physiological role of ion channels. KCNEs are a family of regulatory subunits that interact with a wide range of channels. We have described for the first time a molecular interaction between KCNE4 and the voltage-dependent potassium channel K(V)1.3. The association of KCNE4, which alters the biophysical properties, trafficking and membrane localization of K(V)1.3, functions as an endogenous dominantnegative mechanism. Since both proteins are expressed in the immune system, K(V)1.3/KCNE4 channels may contribute to the fine-tuning of the immune response. Therefore, our results point to KCNE4 as a novel target for immunomodulation. KCNE4 is not the only KCNE which is expressed in leukocytes. All KCNEs (KCNE1-5) are present, and some members demonstrate modulation during proliferation and cancer. In summary, regulatory KCNE subunits are expressed in the immune system. In addition, several voltage-dependent K(+) channels, which could interact with KCNEs, are also detected. Therefore, KCNE subunits may play a yet undiscovered role in the physiology of the immune system. PMID- 20585514 TI - Emerging roles of collapsin response mediator proteins (CRMPs) as regulators of voltage-gated calcium channels and synaptic transmission. AB - Presynaptic N-type voltage-gated Ca(2+) channels (Cav2.2) form part of an extensive macromolecular complex in the presynaptic terminal. Regulation of Cav2.2 is achieved via protein-protein interactions within the terminal and can directly impact transmitter release which is dependent on Ca(2+) influx via these Cav2.2. We recently identified a novel Cav2.2 interacting partner-the collapsin response mediator protein (CRMP).1 CRMPs are a family of five proteins implicated in signal transduction of neurite outgrowth and axonal guidance. We showed that CRMP-2, a wellstudied member of this family, interacted with Cav2.2 via direct binding to cytoplasmic loops of Cav2.2. Depolarization enhanced the interaction. Further studies revealed that CRMP-2 facilitated an increase in Cav2.2 current density by inserting more Cav2.2 at the cell surface. As a consequence of CRMP-2 mediated increase in Ca(2+) influx, release of the excitatory neurotransmitter glutamate was also increased. CRMP-2 localized to synapses where, surprisingly, its overexpression increased synapse size. We hypothesize that the CRMP-2-calcium channel interaction represents a novel mechanism for modulation of Ca(2+) influx into nerve terminals and, hence, of synaptic strength. In this addendum, we further discuss the significance of this study and the possible implications to the field. PMID- 20585515 TI - Impaired GABA(A) receptor endocytosis and its correlation to spatial memory deficits. AB - GABA(A) receptors mediate the majority of fast synaptic inhibition in the mammalian brain. Mechanisms that regulate GABA(A) function are thus of critical importance in modulating overall synaptic inhibition. Phosphorylation of GABA(A) receptor subunits is one such mechanism that leads to the dynamic modulation of GABA(A) receptor function. In particular, phosphorylation of tyrosine residues 365 and 367 (Y365, Y367) within the gamma2 subunit of GABA(A) receptors has been shown in previous in vitro studies to negatively regulate clathrin-dependent endocytosis of GABA(A) receptors and to enhance the efficacy of synaptic inhibition. With the aim of investigating the impact of this phosphorylation dependent modulation of GABA(A) receptors on animal behavior, we recently developed a knock-in mouse in which these critical tyrosine residues within the gamma2 subunit have been mutated to phenylalanines (Y365/7F). These animals exhibited enhanced GABA(A) receptor accumulation at postsynaptic inhibitory synaptic specializations on pyramidal neurons within the hippocampus, primarily due to aberrant trafficking within the endocytic pathway. We found that this enhanced inhibition correlated with a specific deficit in spatial memory in these mice, without modifying a number of other behavioral paradigms. Here, we summarize our recently reported observations and further discuss their possible implications. PMID- 20585516 TI - Complex social waves of giant honeybees provoked by a dummy wasp support the special-agent hypothesis. AB - The social waves in giant honeybees termed as shimmering are more complex than mexican waves. it has been demonstrated1 that shimmering is triggered by special agents at the nest surface. in this paper, we have used a nest that originated by amalgamation of two previously separated nests and stimulated waves by a dummy wasp moved on a miniature cable car. we illustrate the plausibility of the special-agent hypothesis1 also for complex shimmering processes. PMID- 20585517 TI - MICAL-L1: An unusual Rab effector that links EHD1 to tubular recycling endosomes. AB - A key regulator of the slow recycling of receptors and lipids that occurs from the endocytic recycling compartment (ERC) back to the cell surface is EHD1. We have recently identified the Rab8a-interacting protein, MICAL-L1, as a novel binding partner for EHD1 that both recruits and interacts with EHD1 on tubular recycling endosomes. MICAL-L1 belongs to the MICALfamily of proteins that are highly expressed in neurons and involved in plexin-mediated repulsive axon guidance. Interestingly, MICAL-L1 contains a coiled coil region in its C-terminus that is both necessary and sufficient for its localization to the EHD1-containing long tubular membranes of the ERC. Furthermore, MICAL-L1-depletion also impaired recycling of both transferrin and integrin receptors from the ERC back to the plasma membrane. In conclusion, our studies implicate MICAL-L1 as a novel regulator of endocytic recycling, and raises the possibility that additional neuronal-expressed proteins may mediate endocytic events in non-neuronal cells. PMID- 20585518 TI - Fast emotional embodiment can modulate sensory exposure in perceivers. AB - Fear and disgust expressions are not arbitrary social cues. expressing fear maximizes sensory exposure (e.g., increases visual and nasal input), whereas expressing disgust reduces sensory exposure (e.g., decreases visual and nasal input).1 A similar effect of these emotional expressions has recently been found to modify sensory exposure at the level of the central nervous system (attention) in people perceiving these expressions.2 At an attentional level, sensory exposure is increased when perceiving fear and reduced when perceiving disgust. These findings suggest that response preparations are transmitted by expressers to perceivers. However, the processes involved in the transmission of such emotional action tendencies remain unclear. We suggest that emotional contagion by means of grounded cognition theories could be a simple, ecological and straight-forward explanation of this effect. The contagion through embodied simulation of others' emotional states with simple, efficient and very fast facial mimicry may represent the underlying process. PMID- 20585519 TI - Nucleophosmin and nucleolin regulate K-Ras signaling. AB - Ras proteins are laterally segregated into transient nanoclusters on the plasma membrane, a property essential for high fidelity signal transduction through the MAPK pathway. From a proteomic screen we identified nucleophosmin (NPM) and nucleolin as two novel regulators of K-Ras plasma membrane interactions that in turn influence MAP Kinase signaling. NPM and nucleolin are predominately nucleolar proteins but also possess extra-nuclear functions. We showed that a subset of NPM and nucleolin localize to the inner leaflet of the plasma membrane and specifically interact with K-Ras but not H-Ras. This interaction is independent of the activation state of K-Ras, and stabilizes K-Ras membrane levels. NPM expression also increases the fraction of K-Ras in nanoclusters. The increase in clustered K-Ras-GTP enhances signaling through the MAPK pathway. Together these results identify NPM and nucleolin as a new class of K-Ras regulators that modulate signal transduction via the MAPK pathway. PMID- 20585520 TI - The evolution of laughter in great apes and humans. AB - It has long been claimed that human emotional expressions, such as laughter, have evolved from nonhuman displays. The aim of the current study was to test this prediction by conducting acoustic and phylogenetic analyses based on the acoustics of tickle-induced vocalizations of orangutans, gorillas, chimpanzees, bonobos and humans. Results revealed both important similarities and differences among the various species' vocalizations, with the phylogenetic tree reconstructed based on these acoustic data matching the well-established genetic relationships of great apes and humans. These outcomes provide evidence of a common phylogenetic origin of tickle-induced vocalizations in these taxa, which can therefore be termed "laughter" across all five species. Results are consistent with the claims of phylogenetic continuity of emotional expressions. Together with observations made on the use of laughter in great apes and humans, findings of this study further indicate that there were two main periods of selection-driven evolutionary change in laughter within the Hominidae, to a smaller degree, among the great apes and, most distinctively, after the separation of hominins from the last common ancestor with chimpanzees and bonobos. PMID- 20585521 TI - The Aspergillus niger RmsA protein: A node in a genetic network? AB - Many cells and organisms go through polarized growth phases during their life. Cell polarization is achieved by local accumulation of signaling molecules which guide the cytoskeleton and vesicular trafficking to specific parts of the cell and thus ensure polarity establishment and maintenance. Polarization of signaling molecules is also fundamental for the lifestyle of filamentous fungi such as Aspergillus niger and essential for their morphogenesis, development and survival under environmental stress conditions. Considerable advances in our understanding on the protagonists and processes mediating polarized growth in filamentous fungi have been made over the past years. However, how the interplay of different signaling pathways is coordinated has yet to be determined. We found that the A. niger RmsA protein is central for the polarization of actin at the hyphal tip but also of vital importance for the metabolism, viability and stress resistance of A. niger. This suggests that RmsA could occupy an important position in the global network of pathways that balance growth, morphogenesis and survival of A. niger. PMID- 20585522 TI - How to survive within a yeast colony?: Change metabolism or cope with stress? PMID- 20585523 TI - Somatic tetraploidy in vertebrate neurons: Implications in physiology and pathology. AB - The presence of polyploid neurons in the vertebrate nervous system has been a subject of debate since the 1960s. At that time, Purkinje cells were proposed to be tetraploid, but technical limitations impeded to reach a clear conclusion, and the current belief is that most vertebrate neurons are diploid. By using up-to date approaches we have recently demonstrated the existence of a subpopulation of tetraploid retinal ganglion cells (RGCs) in the vertebrate retina. In the chick, these neurons show large somas and extensive dendritic trees and most of them express a marker specific for RGCs innervating a specific lamina of the optic tectum. We have also demonstrated that these neurons are generated in response to nerve growth factor (NGF) acting through the neurotrophin receptor p75 (p75(NTR)), which induces E2F1 activity and cell cycle re-entry in migrating RGC neuroblasts lacking retinoblastoma (Rb) protein. We have also showed that brain derived neurotrophic factor (BDNF) prevents G(2)/M transition in the tetraploid RGCs, thus being crucial for the maintenance of the tetraploid status as well as the survival of these neurons. The realization that tetraploid neurons can be readily observed in the vertebrate nervous system has important physiological consequences, which are discussed in this commentary. PMID- 20585524 TI - Detection of Plasmodium vivax by nested PCR and real-time PCR. AB - Malaria is endemic in the Cukurova region while it is sporadic in other regions of Turkey. Therefore, the laboratory and clinical diagnosis of malaria is important for the treatment of malaria. In this study, 92 blood samples that were taken from the suspected malaria patients for routine diagnosis in a period of 10 years between 1999 and 2009 were analyzed. All of these blood samples were examined by microscopic examinations using Giemsa-stained thick blood films, nested PCR, and real-time PCR. The sensitivity-specificity and positive-negative predictive values for these diagnostic tests were then calculated. It was found that the positive predictive values of microscopic examination of thick blood films, nested PCR, and real-time PCR were 47.8%, 56.5%, and 60.9% for malaria, respectively. The real-time PCR was found to have a specificity of 75% and sensitivity of 100%, while specificity and sensitivity of nested PCR was found 81.2% and 97.7% according to the microscopic examination of thick blood films, respectively. PMID- 20585525 TI - Biological and genetic characterization of Cryptosporidium spp. and Giardia duodenalis isolates from five hydrographical basins in northern Portugal. AB - To understand the situation of water contamination with Cryptosporidium spp. and Giardia spp. in the northern region of Portugal, we have established a long-term program aimed at pinpointing the sources of surface water and environmental contamination, working with the water-supply industry. Here, we describe the results obtained with raw water samples collected in rivers of the 5 hydrographical basins. A total of 283 samples were analyzed using the Method 1623 EPA, USA. Genetic characterization was performed by PCR and sequencing of genes 18S rRNA of Cryptosporidium spp. and beta-giardin of Giardia spp. Infectious stages of the protozoa were detected in 72.8% (206 of 283) of the water samples, with 15.2% (43 of 283) positive for Giardia duodenalis cysts, 9.5% (27 of 283) positive for Cryptosporidium spp. oocysts, and 48.1% (136 of 283) samples positive for both parasites. The most common zoonotic species found were G. duodenalis assemblages A-I, A-II, B, and E genotypes, and Cryptosporidium parvum, Cryptosporidium andersoni, Cryptosporidium hominis, and Cryptosporidium muris. These results suggest that cryptosporidiosis and giardiasis are important public health issues in northern Portugal. To the authors' knowledge, this is the first report evaluating the concentration of environmental stages of Cryptosporidium and Giardia in raw water samples in the northern region of Portugal. PMID- 20585526 TI - Infection status of hospitalized diarrheal patients with gastrointestinal protozoa, bacteria, and viruses in the Republic of Korea. AB - To understand protozoan, viral, and bacterial infections in diarrheal patients, we analyzed positivity and mixed-infection status with 3 protozoans, 4 viruses, and 10 bacteria in hospitalized diarrheal patients during 2004-2006 in the Republic of Korea. A total of 76,652 stool samples were collected from 96 hospitals across the nation. The positivity for protozoa, viruses, and bacteria was 129, 1,759, and 1,797 per 10,000 persons, respectively. Especially, Cryptosporidium parvum was highly mixed-infected with rotavirus among pediatric diarrheal patients (29.5 per 100 C. parvum positive cases), and Entamoeba histolytica was mixed-infected with Clostridium perfringens (10.3 per 100 E. histolytica positive cases) in protozoan-diarrheal patients. Those infected with rotavirus and C. perfringens constituted relatively high proportions among mixed infection cases from January to April. The positivity for rotavirus among viral infection for those aged < or = 5 years was significantly higher, while C. perfringens among bacterial infection was higher for > or = 50 years. The information for association of viral and bacterial infections with enteropathogenic protozoa in diarrheal patients may contribute to improvement of care for diarrhea as well as development of control strategies for diarrheal diseases in Korea. PMID- 20585527 TI - Parents' knowledge about enterobiasis might be one of the most important risk factors for enterobiasis in children. AB - To know the prevalence of Enterobius vermicularis infection and what are the most important risk factors, we evaluated the incidence and risk factors of enterobiasis among children attended in kindergartens in Busan metropolitan city, Republic of Korea. A total of 1,674 children from 21 kindergartens in 11 of 16 autonomous districts of Busan were evaluated for E. vermicularis infection by the cellotape anal swab technique. The overall egg-positive rate for E. vermicularis was 10.7% (179/1,674), and the prevalence of enterobiasis in each kindergarten ranged between 0% and 32.4%. There was an increasing tendency of the egg positive rate according to the population density; the higher the population density communities had, the higher egg-positive rate for E. vermicularis was detected (P = 0.001). Among personal hygiene factors involving children, thumb-sucking (P = 0.036) and fingernail-trimming (P = 0.024) were highly associated with enterobiasis. In addition, taking anthelmintic medications against E. vermicularis infection was strongly associated with enterobiasis (P = 0.014). Moreover, parents' knowledge of enterobiasis was correlated significantly with the incidence of enterobiasis of their children (P = 0.006). In conclusion, we need to consider not only personal hygiene but also parents' knowledge about enterobiasis as a factor in order to develop new strategies for elimination or to complete reduction of enterobiasis in Korea. PMID- 20585528 TI - Carboxylic acids as biomarkers of Biomphalaria alexandrina snails infected with Schistosoma mansoni. AB - Biomphalaria alexandrina snails play an indispensable role in transmission of schistosomiasis. Infection rates in field populations of snails are routinely determined by cercarial shedding neglecting prepatent snail infections, because of lack of a suitable method for diagnosis. The present study aimed at separation and quantification of oxalic, malic, acetic, pyruvic, and fumaric acids using ion suppression reversed-phase high performance liquid chromatography (HPLC) to test the potentiality of these acids to be used as diagnostic and therapeutic biomarkers. The assay was done in both hemolymph and digestive gland-gonad complex (DGG) samples in a total of 300 B. alexandrina snails. All of the studied acids in both the hemolymph and tissue samples except for the fumaric acid in hemolymph appeared to be good diagnostic biomarkers as they provide not only a good discrimination between the infected snails from the control but also between the studied stages of infection from each other. The most sensitive discriminating acid was malic acid in hemolymph samples as it showed the highest F-ratio. Using the Z-score, malic acid was found to be a good potential therapeutic biomarker in the prepatency stage, oxalic acid and acetic acid in the stage of patency, and malic acid and acetic acid at 2 weeks after patency. Quantification of carboxylic acids, using HPLC strategy, was fast, easy, and accurate in prediction of infected and uninfected snails and possibly to detect the stage of infection. It seems also useful for detection of the most suitable acids to be used as drug targets. PMID- 20585529 TI - Epidemiological survey on the infection of intestinal flukes in residents of Muan gun, Jeollanam-do, the Republic of Korea. AB - Infection status of intestinal flukes was investigated in residents of Muan-gun, Jeollanam-do, the Republic of Korea. Total 1,257 fecal samples of residents were examined by formalin-ether sedimentation technique and Kato-Katz thick smear method. Helminth eggs were detected from 95 (7.6%) residents, and eggs of heterophyid flukes and Clonorchis sinensis were found from 62 (4.9%) and 40 (3.2%) cases, respectively. The larger heterophyid eggs, somewhat dark-brown in color and 37.7 x 21.5 microm in average size, and found in 32 (2.6%) out of 62 egg positive cases of heterophyid flukes. To confirm the adult flukes, we performed worm recovery from 12 cases after praziquantel treatment and purgation with MgSO(4). A total of 1,281 adult flukes, assigned to 7 species, were recovered from 9 cooperative cases. Heterophyes nocens (total 981 specimens) was collected from 9 cases, Stictodora fuscata (80) from 7, Gymnophalloides seoi (75) from 5, Pygidiopsis summa (140) from 3, Stellantchasmus falcatus (3) from 2, and Stictodora lari and Acanthotrema felis (each 1 worm) from 1 case each. The intrauterine eggs of S. fuscata collected from the recovered worm were identical with the larger heterophyid eggs detected in the stool examination. By the present study, it was confirmed that A. felis is a new intestinal fluke infecting humans, and residents in Muan-gun, Jeollanam-do are infected with variable species of intestinal trematodes. PMID- 20585530 TI - Extraintestinal migration of Centrorhynchus sp. (Acanthocephala: Centrorhynchidae) in experimentally infected rats. AB - Reptiles were known to serve as paratenic hosts for Centrorhynchus (Acanthocephala: Centrorhynchidae) in Korea, but the infection course in experimental animals was not elucidated yet. In this study, the tiger keelback snakes (Rhabdophis tigrinus) were collected and digested with artificial pepsin solution, and the larvae of Centrorhynchus were recovered from them. Then, the collected larvae were orally infected to rats for developmental observations. In rats, all the larvae were observed outside the intestine on day 3 post-infection (PI), including the mesentery and abdominal muscles. As for the development in rats, the ovary of Centrorhynchus sp. was observed at day 15 PI, and the cement glands were 3 in number. Based on the morphological characteristics, including the arrangement of proboscis hooks, these larvae proved to be a species of Centrorhynchus, and more studies were needed for species identification. PMID- 20585531 TI - Survey of flea infestation in dogs in different geographical regions of Iran. AB - Medically important arthropods, including fleas, play an important role in causing clinical disorders and disease in man and domestic animals. This study was conducted to determine the seasonal flea infestations for domestic dogs from different geographic regions of Iran. A total of 407 fleas, belonging to 5 different species, were recovered from 83 domestic dogs from 3 regions. There was a distinctive pattern of species distribution and infestations with the highest infestation rates observed in a temperate climate and higher rainfall. Additionally, fleas were observed over all seasons, except February and March, with the highest infestation rate observed in August (24.7%) and the lowest rate in January (1.7%). They also parasitize dogs with a different spectrum of species. The cat flea, Ctenocephalides felis (67.5%), exhibited the highest prevalence among all flea species found on dogs. Thus, climatic conditions and seasonal patterns impact on flea infestation and must be considered in developing control programs. PMID- 20585533 TI - A case of probable mixed-infection with Clonorchis sinensis and Fasciola sp.: CT and parasitological findings. AB - We report here a human case probably mixed-infected with Clonorchis sinensis and Fasciola sp. who was diagnosed by computed tomography (CT) scan, serological findings, and/or fecal examination. The patient was a 43-year-old Korean female and was admitted to Kyung Hee University Hospital with the complaints of fever and abdominal pain. On admission, marked eosinophilia was noted in her peripheral blood. CT scan showed specific lesions for clonorchiasis and fascioliasis in the liver, along with lesions suggestive of amebic abscess. Micro-ELISA revealed positive results for the 2 helminthic infections. Eggs of C. sinensis and trophozoites of Entamoeba histolytica were observed in the stool. Treatment with praziquantel followed by metronidazole and tinidazole reduced abnormalities in the liver and eosinophilia. This is the first case report of a possible co infection with 2 kinds of liver flukes in the Republic of Korea. PMID- 20585532 TI - Enzymatic activities of allergen extracts from three species of dust mites and cockroaches commonly found in Korean home. AB - Allergen extracts from dust mites and cockroaches commonly found in Korean homes were used to evaluate their enzymatic activity as they are believed to influence allergenicity. Allergen extracts were prepared from 3 dust mite species (Dermatophagoides farinae, D. pteronyssinus, and Tyrophagus putrescentiae) and 3 cockroach species (Blattella germanica, Periplaneta americana, and P. fuliginosa) maintained in the Korea National Arthropods of Medical Importance Resource Bank. Proteins were extracted in PBS after homogenization using liquid nitrogen. The activities of various enzymes were investigated using the API Zym system. No significant difference in phosphatase, lipase, or glycosidase activity was observed among the 6 allergen extracts, but much difference was observed in protease activity. Protease activity was assessed in more detail by gelatin zymography and the EnzChek assay. Extract from T. putrescentiae showed the highest protease activity, followed by those of the cockroach extracts. Extracts from D. farinae and D. pteronyssinus showed only weak protease activity. Gelatinolytic activity was detected mainly in a 30-kDa protein in D. farinae, a 28-kDa protein in D. pteronyssinus, a > 26-kDa protein in T. putrescentiae, a > 20-kDa protein in B. germanica, and a > 23-kDa protein in P. americana and P. fuliginosa. The information on various enzymatic activities obtained in this study may be useful for future studies. In particular, the strong protease activity found in cockroach extracts could contribute to sensitization to cockroach allergens, which is known to be associated with the development of asthma. PMID- 20585534 TI - An imported case of echinococcosis of the liver in a Korean who traveled to western and central Europe. AB - Echinococcus granulosus, an intestinal tapeworm of dogs and other canids, infects humans in its larval stage and causes human echinococcosis or hydatid disease. In the Republic of Korea, 31 parasite-proven human echinococcosis cases have been reported, most of which were imported from the Middle East. We recently examined a 61-year-old Korean man who had a large cystic mass in his liver. ELISA was negative for tissue parasitic infections, including echinococcosis, cysticercosis, paragonimiasis, and sparganosis. The patient underwent surgery to remove the cyst, and the resected cyst was processed histopathologically for microscopic examinations. In sectioned cyst tissue, necrotizing protoscolices with disintegrated hooklets of E. granulosus were found. In some areas, only freed, fragmented hooklets were detected. The patient had traveled to western and central Europe in 1996, and had no other history of overseas travel. We report our patient as a hepatic echinococcosis case which was probably imported from Europe. PMID- 20585535 TI - A human case of Hymenolepis diminuta in a child from eastern Sicily. AB - We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols. PMID- 20585536 TI - Suppressed CD31 expression in sarcoma-180 tumors after injection with Toxoplasma gondii lysate antigen in BALB/c mice. AB - The anti-tumorigenic effects of Toxoplasma gondii (RH) antigens were studied in a murine sarcoma-180 tumor model. To determine the anti-tumor effects, the reduction in tumor size and expression of CD31 (an angiogenesis marker in the tumor tissue) were examined after injection of BALB/c mice with T. gondii lysate antigen (TLA) or formalin-fixed, proliferation-inhibited, T. gondii tachyzoites. Tumors were successfully produced by an intradermal injection of sarcoma-180 cells with plain Matrigel in the mid-backs of mice. After injection with TLA or formalin-fixed T. gondii tachyzoites, the increase in tumor size and weight nearly stopped while tumor growth continued in control mice that were injected with PBS. CD31 expression in TLA-treated or formalin-fixed T. gondii-injected mice was lower than the control mice. Accordingly, the present study shows that the treatment of mice with formalin-fixed T. gondii or TLA in the murine sarcoma 180 tumor model results in a decrease of both tumor size and CD31 expression. PMID- 20585537 TI - Primaquine administration after falciparum malaria treatment in malaria hypoendemic areas with high incidence of falciparum and vivax mixed infection: pros and cons. AB - Mixed infections of Plasmodium falciparum and Plasmodium vivax is high (approximately 30%) in some malaria hypoendemic areas where the patients present with P. falciparum malaria diagnosed by microscopy. Conventional treatment of P. falciparum with concurrent chloroquine and 14 days of primaquine for all falciparum malaria patients may be useful in areas where mixed falciparum and vivax infections are high and common and also with mild or moderate G6PD deficiency in the population even with or without subpatent vivax mixed infection. It will be possibly cost-effective to reduce subsequent vivax illness if the patients have mixed vivax infection. Further study to prove this hypothesis may be warranted. PMID- 20585538 TI - Appropriate time for primaquine treatment to reduce Plasmodium falciparum transmission in hypoendemic areas. AB - Artemesinin-combination therapies (ACT) for falciparum malaria reduce gametocyte carriage, and therefore reduce transmission. Artemisinin derivatives will act against only young gametocytes whereas primaquine acts on mature gametocytes which are present usually in the circulation at the time when the patient presents for treatment. Both artemisinin derivatives and primaquine have short half-lives, less than 1 hr and 7 hr, respectively. Therefore, asexual parasites or young gametocytes remain after completed ACT. A single dose of primaquine (0.50-0.75 mg base/kg) at the end of ACT can kill only mature gametocytes but cannot kill young gametocytes (if present). Remaining asexual forms after completion of ACT course, e.g., artesunate-mefloquine for 3 days, may develop to mature gametocytes 7-15 days later. Thus, an additional dose of primaquine (0.50 0.75 mg base/kg) given 2 weeks after ACT completion may be beneficial for killing remaining mature gametocytes and contribute to more interruption of Plasmodium falciparum transmission than giving only 1 single dose of primaquine just after completing ACT. PMID- 20585539 TI - Production of polyclonal antibodies against the tegument of sparganum (plerocercoid of Spirometra mansoni) and its immunolocalization. AB - In a previous study, the author developed a method for separation of the tegument of spargana (plerocercoids of Spirometra mansoni) from the parenchyme using urea. The present study, as a next step, was performed to evaluate which molecules are present in the outer tegument. Two major proteins, 180 and 200 kDa, are present in the tegument and we could make polyclonal antibodies against these molecules. Their immunolocalization was processed and the outermost layer of the spargana showed strong positive staining. Conclusively, we could confirm that the 180 and 200 kDa molecules might be tightly bound membrane proteins in the tegument of spargana. PMID- 20585540 TI - Nonlinearity of mechanochemical motions in motor proteins. AB - The assumption of linear response of protein molecules to thermal noise or structural perturbations, such as ligand binding or detachment, is broadly used in the studies of protein dynamics. Conformational motions in proteins are traditionally analyzed in terms of normal modes and experimental data on thermal fluctuations in such macromolecules is also usually interpreted in terms of the excitation of normal modes. We have chosen two important protein motors--myosin V and kinesin KIF1A--and performed numerical investigations of their conformational relaxation properties within the coarse-grained elastic network approximation. We have found that the linearity assumption is deficient for ligand-induced conformational motions and can even be violated for characteristic thermal fluctuations. The deficiency is particularly pronounced in KIF1A where the normal mode description fails completely in describing functional mechanochemical motions. These results indicate that important assumptions of the theory of protein dynamics may need to be reconsidered. Neither a single normal mode nor a superposition of such modes yields an approximation of strongly nonlinear dynamics. PMID- 20585541 TI - NeuroML: a language for describing data driven models of neurons and networks with a high degree of biological detail. AB - Biologically detailed single neuron and network models are important for understanding how ion channels, synapses and anatomical connectivity underlie the complex electrical behavior of the brain. While neuronal simulators such as NEURON, GENESIS, MOOSE, NEST, and PSICS facilitate the development of these data driven neuronal models, the specialized languages they employ are generally not interoperable, limiting model accessibility and preventing reuse of model components and cross-simulator validation. To overcome these problems we have used an Open Source software approach to develop NeuroML, a neuronal model description language based on XML (Extensible Markup Language). This enables these detailed models and their components to be defined in a standalone form, allowing them to be used across multiple simulators and archived in a standardized format. Here we describe the structure of NeuroML and demonstrate its scope by converting into NeuroML models of a number of different voltage- and ligand-gated conductances, models of electrical coupling, synaptic transmission and short-term plasticity, together with morphologically detailed models of individual neurons. We have also used these NeuroML-based components to develop an highly detailed cortical network model. NeuroML-based model descriptions were validated by demonstrating similar model behavior across five independently developed simulators. Although our results confirm that simulations run on different simulators converge, they reveal limits to model interoperability, by showing that for some models convergence only occurs at high levels of spatial and temporal discretisation, when the computational overhead is high. Our development of NeuroML as a common description language for biophysically detailed neuronal and network models enables interoperability across multiple simulation environments, thereby improving model transparency, accessibility and reuse in computational neuroscience. PMID- 20585542 TI - Using entropy maximization to understand the determinants of structural dynamics beyond native contact topology. AB - Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics. PMID- 20585543 TI - Revisiting date and party hubs: novel approaches to role assignment in protein interaction networks. AB - The idea of "date" and "party" hubs has been influential in the study of protein protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here, we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. However, we find significant correlations between interaction centrality and the functional similarity of the interacting proteins. We suggest that thinking in terms of a date/party dichotomy for hubs in protein interaction networks is not meaningful, and it might be more useful to conceive of roles for protein-protein interactions rather than for individual proteins. PMID- 20585544 TI - Fast- or slow-inactivated state preference of Na+ channel inhibitors: a simulation and experimental study. AB - Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the "steady-state slow inactivation curve"), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow inactivated state preference are unreliable and should be re-evaluated. PMID- 20585545 TI - A cell-based model for quorum sensing in heterogeneous bacterial colonies. AB - Although bacteria are unicellular organisms, they have the ability to act in concert by synthesizing and detecting small diffusing autoinducer molecules. The phenomenon, known as quorum sensing, has mainly been proposed to serve as a means for cell-density measurement. Here, we use a cell-based model of growing bacterial microcolonies to investigate a quorum-sensing mechanism at a single cell level. We show that the model indeed predicts a density-dependent behavior, highly dependent on local cell-clustering and the geometry of the space where the colony is evolving. We analyze the molecular network with two positive feedback loops to find the multistability regions and show how the quorum-sensing mechanism depends on different model parameters. Specifically, we show that the switching capability of the network leads to more constraints on parameters in a natural environment where the bacteria themselves produce autoinducer than compared to situations where autoinducer is introduced externally. The cell-based model also allows us to investigate mixed populations, where non-producing cheater cells are shown to have a fitness advantage, but still cannot completely outcompete producer cells. Simulations, therefore, are able to predict the relative fitness of cheater cells from experiments and can also display and account for the paradoxical phenomenon seen in experiments; even though the cheater cells have a fitness advantage in each of the investigated groups, the overall effect is an increase in the fraction of producer cells. The cell-based type of model presented here together with high-resolution experiments will play an integral role in a more explicit and precise comparison of models and experiments, addressing quorum sensing at a cellular resolution. PMID- 20585547 TI - Understanding adaptation in large populations. PMID- 20585546 TI - Rule-based cell systems model of aging using feedback loop motifs mediated by stress responses. AB - Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-kappaB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype. PMID- 20585548 TI - Dosage-sensitive function of retinoblastoma related and convergent epigenetic control are required during the Arabidopsis life cycle. AB - The plant life cycle alternates between two distinct multi-cellular generations, the reduced gametophytes and the dominant sporophyte. Little is known about how generation-specific cell fate, differentiation, and development are controlled by the core regulators of the cell cycle. In Arabidopsis, RETINOBLASTOMA RELATED (RBR), an evolutionarily ancient cell cycle regulator, controls cell proliferation, differentiation, and regulation of a subset of Polycomb Repressive Complex 2 (PRC2) genes and METHYLTRANSFERASE 1 (MET1) in the male and female gametophytes, as well as cell fate establishment in the male gametophyte. Here we demonstrate that RBR is also essential for cell fate determination in the female gametophyte, as revealed by loss of cell-specific marker expression in all the gametophytic cells that lack RBR. Maintenance of genome integrity also requires RBR, because diploid plants heterozygous for rbr (rbr/RBR) produce an abnormal portion of triploid offspring, likely due to gametic genome duplication. While the sporophyte of the diploid mutant plants phenocopied wild type due to the haplosufficiency of RBR, genetic analysis of tetraploid plants triplex for rbr (rbr/rbr/rbr/RBR) revealed that RBR has a dosage-dependent pleiotropic effect on sporophytic development, trichome differentiation, and regulation of PRC2 subunit genes CURLY LEAF (CLF) and VERNALIZATION 2 (VRN2), and MET1 in leaves. There were, however, no obvious cell cycle and cell proliferation defects in these plant tissues, suggesting that a single functional RBR copy in tetraploids is capable of maintaining normal cell division but is not sufficient for distinct differentiation and developmental processes. Conversely, in leaves of mutants in sporophytic PRC2 subunits, trichome differentiation was also affected and expression of RBR and MET1 was reduced, providing evidence for a RBR-PRC2-MET1 regulatory feedback loop involved in sporophyte development. Together, dosage sensitive RBR function and its genetic interaction with PRC2 genes and MET1 must have been recruited during plant evolution to control distinct generation specific cell fate, differentiation, and development. PMID- 20585549 TI - The cyclin-A CYCA1;2/TAM is required for the meiosis I to meiosis II transition and cooperates with OSD1 for the prophase to first meiotic division transition. AB - Meiosis halves the chromosome number because its two divisions follow a single round of DNA replication. This process involves two cell transitions, the transition from prophase to the first meiotic division (meiosis I) and the unique meiosis I to meiosis II transition. We show here that the A-type cyclin CYCA1;2/TAM plays a major role in both transitions in Arabidopsis. A series of tam mutants failed to enter meiosis II and thus produced diploid spores and functional diploid gametes. These diploid gametes had a recombined genotype produced through the single meiosis I division. In addition, by combining the tam 2 mutation with AtSpo11-1 and Atrec8, we obtained plants producing diploid gametes through a mitotic-like division that were genetically identical to their parents. Thus tam alleles displayed phenotypes very similar to that of the previously described osd1 mutant. Combining tam and osd1 mutations leads to a failure in the prophase to meiosis I transition during male meiosis and to the production of tetraploid spores and gametes. This suggests that TAM and OSD1 are involved in the control of both meiotic transitions. PMID- 20585551 TI - Evidence that adaptation in Drosophila is not limited by mutation at single sites. AB - Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes. This view is difficult to reconcile, however, with the observation that adaptation to anthropogenic changes, such as the introduction of pesticides, can occur very rapidly. Here we investigate adaptation at a key insecticide resistance locus (Ace) in Drosophila melanogaster and show that multiple simple and complex resistance alleles evolved quickly and repeatedly within individual populations. Our results imply that the current effective population size of modern D. melanogaster populations is likely to be substantially larger (> or = 100-fold) than commonly believed. This discrepancy arises because estimates of the effective population size are generally derived from levels of standing variation and thus reveal long-term population dynamics dominated by sharp--even if infrequent--bottlenecks. The short-term effective population sizes relevant for strong adaptation, on the other hand, might be much closer to census population sizes. Adaptation in Drosophila may therefore not be limited by waiting for mutations at single sites, and complex adaptive alleles can be generated quickly without fixation of intermediate states. Adaptive events should also commonly involve the simultaneous rise in frequency of independently generated adaptive mutations. These so-called soft sweeps have very distinct effects on the linked neutral polymorphisms compared to the standard hard sweeps in mutation-limited scenarios. Methods for the mapping of adaptive mutations or association mapping of evolutionarily relevant mutations may thus need to be reconsidered. PMID- 20585550 TI - Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. AB - Akt represents a nodal point between the Insulin receptor and TOR signaling, and its activation by phosphorylation controls cell proliferation, cell size, and metabolism. The activity of Akt must be carefully balanced, as increased Akt signaling is frequently associated with cancer and as insufficient Akt signaling is linked to metabolic disease and diabetes mellitus. Using a genome-wide RNAi screen in Drosophila cells in culture, and in vivo analyses in the third instar wing imaginal disc, we studied the regulatory circuitries that define dAkt activation. We provide evidence that negative feedback regulation of dAkt occurs during normal Drosophila development in vivo. Whereas in cell culture dAkt is regulated by S6 Kinase (S6K)-dependent negative feedback, this feedback inhibition only plays a minor role in vivo. In contrast, dAkt activation under wild-type conditions is defined by feedback inhibition that depends on TOR Complex 1 (TORC1), but is S6K-independent. This feedback inhibition is switched from TORC1 to S6K only in the context of enhanced TORC1 activity, as triggered by mutations in tsc2. These results illustrate how the Akt-TOR pathway dynamically adapts the routing of negative feedback in response to the activity load of its signaling circuit in vivo. PMID- 20585552 TI - Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator. AB - Arginine is a crucial amino acid that serves to modulate the cellular immune response during infection. Arginine is also a common substrate for both inducible nitric oxide synthase (iNOS) and arginase. The generation of nitric oxide from arginine is responsible for efficient immune response and cytotoxicity of host cells to kill the invading pathogens. On the other hand, the conversion of arginine to ornithine and urea via the arginase pathway can support the growth of bacterial and parasitic pathogens. The competition between iNOS and arginase for arginine can thus contribute to the outcome of several parasitic and bacterial infections. There are two isoforms of vertebrate arginase, both of which catalyze the conversion of arginine to ornithine and urea, but they differ with regard to tissue distribution and subcellular localization. In the case of infection with Mycobacterium, Leishmania, Trypanosoma, Helicobacter, Schistosoma, and Salmonella spp., arginase isoforms have been shown to modulate the pathology of infection by various means. Despite the existence of a considerable body of evidence about mammalian arginine metabolism and its role in immunology, the critical choice to divert the host arginine pool by pathogenic organisms as a survival strategy is still a mystery in infection biology. PMID- 20585553 TI - Beauty is in the eye of the beholder: proteins can recognize binding sites of homologous proteins in more than one way. AB - Understanding the mechanisms of protein-protein interaction is a fundamental problem with many practical applications. The fact that different proteins can bind similar partners suggests that convergently evolved binding interfaces are reused in different complexes. A set of protein complexes composed of non homologous domains interacting with homologous partners at equivalent binding sites was collected in 2006, offering an opportunity to investigate this point. We considered 433 pairs of protein-protein complexes from the ABAC database (AB and AC binary protein complexes sharing a homologous partner A) and analyzed the extent of physico-chemical similarity at the atomic and residue level at the protein-protein interface. Homologous partners of the complexes were superimposed using Multiprot, and similar atoms at the interface were quantified using a five class grouping scheme and a distance cut-off. We found that the number of interfacial atoms with similar properties is systematically lower in the non homologous proteins than in the homologous ones. We assessed the significance of the similarity by bootstrapping the atomic properties at the interfaces. We found that the similarity of binding sites is very significant between homologous proteins, as expected, but generally insignificant between the non-homologous proteins that bind to homologous partners. Furthermore, evolutionarily conserved residues are not colocalized within the binding sites of non-homologous proteins. We could only identify a limited number of cases of structural mimicry at the interface, suggesting that this property is less generic than previously thought. Our results support the hypothesis that different proteins can interact with similar partners using alternate strategies, but do not support convergent evolution. PMID- 20585554 TI - On the use of variance per genotype as a tool to identify quantitative trait interaction effects: a report from the Women's Genome Health Study. AB - Testing for genetic effects on mean values of a quantitative trait has been a very successful strategy. However, most studies to date have not explored genetic effects on the variance of quantitative traits as a relevant consequence of genetic variation. In this report, we demonstrate that, under plausible scenarios of genetic interaction, the variance of a quantitative trait is expected to differ among the three possible genotypes of a biallelic SNP. Leveraging this observation with Levene's test of equality of variance, we propose a novel method to prioritize SNPs for subsequent gene-gene and gene-environment testing. This method has the advantageous characteristic that the interacting covariate need not be known or measured for a SNP to be prioritized. Using simulations, we show that this method has increased power over exhaustive search under certain conditions. We further investigate the utility of variance per genotype by examining data from the Women's Genome Health Study. Using this dataset, we identify new interactions between the LEPR SNP rs12753193 and body mass index in the prediction of C-reactive protein levels, between the ICAM1 SNP rs1799969 and smoking in the prediction of soluble ICAM-1 levels, and between the PNPLA3 SNP rs738409 and body mass index in the prediction of soluble ICAM-1 levels. These results demonstrate the utility of our approach and provide novel genetic insight into the relationship among obesity, smoking, and inflammation. PMID- 20585555 TI - The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. AB - Human chromosome 14q32.2 harbors the germline-derived primary DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization derived secondary MEG3-DMR, together with multiple imprinted genes. Although previous studies in cases with microdeletions and epimutations affecting both DMRs and paternal/maternal uniparental disomy 14-like phenotypes argue for a critical regulatory function of the two DMRs for the 14q32.2 imprinted region, the precise role of the individual DMR remains to be clarified. We studied an infant with upd(14)pat body and placental phenotypes and a heterozygous microdeletion involving the IG-DMR alone (patient 1) and a neonate with upd(14)pat body, but no placental phenotype and a heterozygous microdeletion involving the MEG3-DMR alone (patient 2). The results generated from the analysis of these two patients imply that the IG-DMR and the MEG3-DMR function as imprinting control centers in the placenta and the body, respectively, with a hierarchical interaction for the methylation pattern in the body governed by the IG-DMR. To our knowledge, this is the first study demonstrating an essential long range imprinting regulatory function for the secondary DMR. PMID- 20585556 TI - Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post hemifusion step. AB - Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Galphaq mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients. PMID- 20585557 TI - Fungal cell gigantism during mammalian infection. AB - The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens. PMID- 20585558 TI - Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum. AB - Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine. PMID- 20585560 TI - DNA watermarking of infectious agents: progress and prospects. PMID- 20585559 TI - Cryptococcal cell morphology affects host cell interactions and pathogenicity. AB - Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in vivo, producing cells up to 100 microm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aDelta pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection. PMID- 20585561 TI - A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics. AB - Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Drosophila kinome for factors required for vaccinia infection. We identified seven genes including the three subunits of AMPK as promoting vaccinia infection. AMPK not only facilitated infection in insect cells, but also in mammalian cells. Moreover, we found that AMPK is required for macropinocytosis, a major endocytic entry pathway for vaccinia. Furthermore, we show that AMPK contributes to other virus-independent actin-dependent processes including lamellipodia formation and wound healing, independent of the known AMPK activators LKB1 and CaMKK. Therefore, AMPK plays a highly conserved role in poxvirus infection and actin dynamics independent of its role as an energy regulator. PMID- 20585562 TI - Tetherin restricts productive HIV-1 cell-to-cell transmission. AB - The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or DeltaVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of DeltaVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread. PMID- 20585563 TI - Body fat and dairy product intake in lactase persistent and non-persistent children and adolescents. AB - BACKGROUND: Lactase non-persistent (LNP) individuals may be lactose intolerant and therefore on a more restricted diet concerning milk and milk products compared to lactase persistent (LP) individuals. This may have an impact on body fat mass. OBJECTIVE: This study examines if LP and LNP children and adolescents, defined by genotyping for the LCT-13910 C > T polymorphism, differ from each other with regard to milk and milk product intake, and measures of body fat mass. DESIGN: Children (n=298, mean age 9.6 years) and adolescents (n=386, mean age 15.6 years), belonging to the Swedish part of the European Youth Heart Study, were genotyped for the LCT-13910 C > T polymorphism. Dietary intakes of reduced and full-fat dairy varieties were determined. RESULTS: LNP (CC genotype) subjects consumed less milk, soured milk and yoghurt compared to LP (CT/TT genotype) subjects (p<0.001). Subsequent partitioning for age group attenuated this observation (p=0.002 for children and p=0.023 in adolescents). Six subjects were reported by parents to be 'lactose intolerant', none of whom were LNP. LNP children and adolescents consumed significantly less reduced fat milk and milk products than LP children and adolescents (p=0.009 for children and p=0.001 for adolescents). CONCLUSIONS: We conclude that LP is linked to an overall higher milk and dairy intake, but is not linked to higher body fat mass in children and adolescents. PMID- 20585564 TI - A locomotor innovation enables water-land transition in a marine fish. AB - BACKGROUND: Morphological innovations that significantly enhance performance capacity may enable exploitation of new resources and invasion of new ecological niches. The invasion of land from the aquatic realm requires dramatic structural and physiological modifications to permit survival in a gravity-dominated, aerial environment. Most fishes are obligatorily aquatic, with amphibious fishes typically making slow-moving and short forays on to land. METHODOLOGY/PRINCIPAL FINDINGS: Here I describe the behaviors and movements of a little known marine fish that moves extraordinarily rapidly on land. I found that the Pacific leaping blenny, Alticus arnoldorum, employs a tail-twisting movement on land, previously unreported in fishes. Focal point behavioral observations of Alticus show that they have largely abandoned the marine realm, feed and reproduce on land, and even defend terrestrial territories. Comparisons of these blennies' terrestrial kinematic and kinetic (i.e., force) measurements with those of less terrestrial sister genera show A. arnoldorum move with greater stability and locomotor control, and can move away more rapidly from impending threats. CONCLUSIONS/SIGNIFICANCE: My results demonstrate that axial tail twisting serves as a key innovation enabling invasion of a novel marine niche. This paper highlights the potential of using this system to address general evolutionary questions about water-land transitions and niche invasions. PMID- 20585565 TI - Community-based measures for mitigating the 2009 H1N1 pandemic in China. AB - Since the emergence of influenza A/H1N1 pandemic virus in March-April 2009, very stringent interventions including Fengxiao were implemented to prevent importation of infected cases and decelerate the disease spread in mainland China. The extent to which these measures have been effective remains elusive. We sought to investigate the effectiveness of Fengxiao that may inform policy decisions on improving community-based interventions for management of on-going outbreaks in China, in particular during the Spring Festival in mid-February 2010 when nationwide traveling will be substantially increased. We obtained data on initial laboratory-confirmed cases of H1N1 in the province of Shaanxi and used Markov-chain Monte-Carlo (MCMC) simulations to estimate the reproduction number. Given the estimates for the exposed and infectious periods of the novel H1N1 virus, we estimated a mean reproduction number of 1.68 (95% CI 1.45-1.92) and other A/H1N1 epidemiological parameters. Our results based on a spatially stratified population dynamical model show that the early implementation of Fengxiao can delay the epidemic peak significantly and prevent the disease spread to the general population but may also, if not implemented appropriately, cause more severe outbreak within universities/colleges, while late implementation of Fengxiao can achieve nothing more than no implementation. Strengthening local control strategies (quarantine and hygiene precaution) is much more effective in mitigating outbreaks and inhibiting the successive waves than implementing Fengxiao. Either strong mobility or high transport-related transmission rate during the Spring Festival holiday will not reverse the ongoing outbreak, but both will result in a large new wave. The findings suggest that Fengxiao and travel precautions should not be relaxed unless strict measures of quarantine, isolation, and hygiene precaution practices are put in place. Integration and prompt implementation of these interventions can significantly reduce the overall attack rate of pandemic outbreaks. PMID- 20585566 TI - NleG Type 3 effectors from enterohaemorrhagic Escherichia coli are U-Box E3 ubiquitin ligases. AB - NleG homologues constitute the largest family of Type 3 effectors delivered by pathogenic E. coli, with fourteen members in the enterohaemorrhagic (EHEC) O157:H7 strain alone. Identified recently as part of the non-LEE-encoded (Nle) effector set, this family remained uncharacterised and shared no sequence homology to other proteins including those of known function. The C-terminal domain of NleG2-3 (residues 90 to 191) is the most conserved region in NleG proteins and was solved by NMR. Structural analysis of this structure revealed the presence of a RING finger/U-box motif. Functional assays demonstrated that NleG2-3 as well as NleG5-1, NleG6-2 and NleG9' family members exhibited a strong autoubiquitination activity in vitro; a characteristic usually expressed by eukaryotic ubiquitin E3 ligases. When screened for activity against a panel of 30 human E2 enzymes, the NleG2-3 and NleG5-1 homologues showed an identical profile with only UBE2E2, UBE2E3 and UBE2D2 enzymes supporting NleG activity. Fluorescence polarization analysis yielded a binding affinity constant of 56+/-2 microM for the UBE2D2/NleG5-1 interaction, a value comparable with previous studies on E2/E3 affinities. The UBE2D2 interaction interface on NleG2-3 defined by NMR chemical shift perturbation and mutagenesis was shown to be generally similar to that characterised for human RING finger ubiquitin ligases. The alanine substitutions of UBE2D2 residues Arg5 and Lys63, critical for activation of eukaryotic E3 ligases, also significantly decreased both NleG binding and autoubiquitination activity. These results demonstrate that bacteria-encoded NleG effectors are E3 ubiquitin ligases analogous to RING finger and U-box enzymes in eukaryotes. PMID- 20585567 TI - The enteropathogenic E. coli effector EspF targets and disrupts the nucleolus by a process regulated by mitochondrial dysfunction. AB - The nucleolus is a multifunctional structure within the nucleus of eukaryotic cells and is the primary site of ribosome biogenesis. Almost all viruses target and disrupt the nucleolus--a feature exclusive to this pathogen group. Here, using a combination of bio-imaging, genetic and biochemical analyses, we demonstrate that the enteropathogenic E. coli (EPEC) effector protein EspF specifically targets the nucleolus and disrupts a subset of nucleolar factors. Driven by a defined N-terminal nucleolar targeting domain, EspF causes the complete loss from the nucleolus of nucleolin, the most abundant nucleolar protein. We also show that other bacterial species disrupt the nucleolus, dependent on their ability to deliver effector proteins into the host cell. Moreover, we uncover a novel regulatory mechanism whereby nucleolar targeting by EspF is strictly controlled by EPEC's manipulation of host mitochondria. Collectively, this work reveals that the nucleolus may be a common feature of bacterial pathogenesis and demonstrates that a bacterial pathogen has evolved a highly sophisticated mechanism to enable spatio-temporal control over its virulence proteins. PMID- 20585568 TI - Formation of complexes at plasmodesmata for potyvirus intercellular movement is mediated by the viral protein P3N-PIPO. AB - Intercellular transport of viruses through cytoplasmic connections, termed plasmodesmata (PD), is essential for systemic infection in plants by viruses. Previous genetic and ultrastructural data revealed that the potyvirus cyclindrical inclusion (CI) protein is directly involved in cell-to-cell movement, likely through the formation of conical structures anchored to and extended through PD. In this study, we demonstrate that plasmodesmatal localization of CI in N. benthamiana leaf cells is modulated by the recently discovered potyviral protein, P3N-PIPO, in a CI:P3N-PIPO ratio-dependent manner. We show that P3N-PIPO is a PD-located protein that physically interacts with CI in planta. The early secretory pathway, rather than the actomyosin motility system, is required for the delivery of P3N-PIPO and CI to PD. Moreover, CI mutations that disrupt virus cell-to-cell movement compromise PD-localization capacity. These data suggest that the CI and P3N-PIPO complex coordinates the formation of PD-associated structures that facilitate the intercellular movement of potyviruses in infected plants. PMID- 20585569 TI - Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. AB - Neurological impairments are frequently detected in children surviving cerebral malaria (CM), the most severe neurological complication of infection with Plasmodium falciparum. The pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. In the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatment. Infection of C57BL/6 and Swiss (SW) mice with Plasmodium berghei ANKA (PbA) or a lethal strain of Plasmodium yoelii XL (PyXL), respectively, resulted in documented CM and sustained persistent cognitive damage detected by a battery of behavioral tests after cure of the acute parasitic disease with chloroquine therapy. Strikingly, cognitive impairment was still present 30 days after the initial infection. In contrast, BALB/c mice infected with PbA, C57BL6 infected with Plasmodium chabaudi chabaudi and SW infected with non lethal Plasmodium yoelii NXL (PyNXL) did not develop signs of CM, were cured of the acute parasitic infection by chloroquine, and showed no persistent cognitive impairment. Reactive oxygen species have been reported to mediate neurological injury in CM. Increased production of malondialdehyde (MDA) and conjugated dienes was detected in the brains of PbA infected C57BL/6 mice with CM, indicating high oxidative stress. Treatment of PbA infected C57BL/6 mice with additive antioxidants together with chloroquine at the first signs of CM prevented the development of persistent cognitive damage. These studies provide new insights into the natural history of cognitive dysfunction after rescue therapy for CM that may have clinical relevance, and may also be relevant to cerebral sequelae of sepsis and other disorders. PMID- 20585570 TI - Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA. AB - Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to alpha(5)beta(1) integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis. PMID- 20585571 TI - Human cytomegalovirus UL29/28 protein interacts with components of the NuRD complex which promote accumulation of immediate-early RNA. AB - Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs. PMID- 20585572 TI - Role of PKR and Type I IFNs in viral control during primary and secondary infection. AB - Type I interferons (IFNs) are known to mediate viral control, and also promote survival and expansion of virus-specific CD8+ T cells. However, it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct. One of the best-characterized anti-viral signaling mechanisms of Type I IFNs is mediated by the IFN-inducible dsRNA activated protein kinase, PKR. Here, we have investigated the role of PKR and Type I IFNs in regulating viral clearance and CD8+ T cell response during primary and secondary viral infections. Our studies demonstrate differential requirement for PKR, in viral control versus elicitation of CD8+ T cell responses during primary infection of mice with lymphocytic choriomeningitis virus (LCMV). PKR-deficient mice mounted potent CD8+ T cell responses, but failed to effectively control LCMV. The compromised LCMV control in the absence of PKR was multifactorial, and linked to less effective CD8+ T cell-mediated viral suppression, enhanced viral replication in cells, and lower steady state expression levels of IFN-responsive genes. Moreover, we show that despite normal expansion of memory CD8+ T cells and differentiation into effectors during a secondary response, effective clearance of LCMV but not vaccinia virus required PKR activity in infected cells. In the absence of Type I IFN signaling, secondary effector CD8+ T cells were ineffective in controlling both LCMV and vaccinia virus replication in vivo. These findings provide insight into cellular pathways of Type I IFN actions, and highlight the under-appreciated importance of innate immune mechanisms of viral control during secondary infections, despite the accelerated responses of memory CD8+ T cells. Additionally, the results presented here have furthered our understanding of the immune correlates of anti-viral protective immunity, which have implications in the rational design of vaccines. PMID- 20585573 TI - Translational selection is ubiquitous in prokaryotes. AB - Codon usage bias in prokaryotic genomes is largely a consequence of background substitution patterns in DNA, but highly expressed genes may show a preference towards codons that enable more efficient and/or accurate translation. We introduce a novel approach based on supervised machine learning that detects effects of translational selection on genes, while controlling for local variation in nucleotide substitution patterns represented as sequence composition of intergenic DNA. A cornerstone of our method is a Random Forest classifier that outperformed previous distance measure-based approaches, such as the codon adaptation index, in the task of discerning the (highly expressed) ribosomal protein genes by their codon frequencies. Unlike previous reports, we show evidence that translational selection in prokaryotes is practically universal: in 460 of 461 examined microbial genomes, we find that a subset of genes shows a higher codon usage similarity to the ribosomal proteins than would be expected from the local sequence composition. These genes constitute a substantial part of the genome--between 5% and 33%, depending on genome size--while also exhibiting higher experimentally measured mRNA abundances and tending toward codons that match tRNA anticodons by canonical base pairing. Certain gene functional categories are generally enriched with, or depleted of codon-optimized genes, the trends of enrichment/depletion being conserved between Archaea and Bacteria. Prominent exceptions from these trends might indicate genes with alternative physiological roles; we speculate on specific examples related to detoxication of oxygen radicals and ammonia and to possible misannotations of asparaginyl-tRNA synthetases. Since the presence of codon optimizations on genes is a valid proxy for expression levels in fully sequenced genomes, we provide an example of an "adaptome" by highlighting gene functions with expression levels elevated specifically in thermophilic Bacteria and Archaea. PMID- 20585574 TI - Detection of plant DNA in the bronchoalveolar lavage of patients with ventilator associated pneumonia. AB - BACKGROUND: Hospital-acquired infections such as nosocomial pneumonia are a serious cause of mortality for hospitalized patients, especially for those admitted to intensive care units (ICUs). Despite the number of the studies reported to date, the causative agents of pneumonia are not completely known. Herein, we found by molecular technique that vegetable and tobacco DNA may be detected in the bronchoalveolar lavage from patients with ventilator-associated pneumonia (VAP). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we studied bronchoalveolar lavage (BAL) from patients admitted to ICUs with ventilator associated pneumonia. BAL fluids were assessed with molecular tests, culture and blood culture. We successfully identified plant DNA in six patients out of 106 (6%) with ventilator-associated pneumonia. Inhalation was confirmed in four cases and suspected in the other two cases. Inhalation was significantly frequent in patients with plant DNA (four out of six patients) than those without plant DNA (three out of 100 patients) (P<0.001). Nicotiana tabacum chloroplast DNA was identified in three patients who were smokers (cases 2, 3 and 6). Cucurbita pepo, Morus bombycis and Triticum aestivum DNA were identified in cases 1, 4 and 5 respectively. Twenty-three different bacterial species, two viruses and five fungal species were identified from among these six patients by using molecular and culture techniques. Several of the pathogenic microorganisms identified are reported to be food-borne or tobacco plant-associated pathogens. CONCLUSIONS/SIGNIFICANCE: Our study shows that plants DNA may be identified in the BAL fluid of pneumonia patients, especially when exploring aspiration pneumonia, but the significance of the presence of plant DNA and its role in the pathogenesis of pneumonia is unknown and remains to be investigated. However, the identification of these plants may be a potential marker of aspiration in patients with pneumonia. PMID- 20585575 TI - Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. AB - During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and characteristic telomerase pattern. We analyzed the clonogenic activity of SP cells under hypoxic conditions and the differentiation capacity in vitro to adipogenic and osteogenic lineages. Finally, we demonstrated the functional capability of endometrial SP to develop human endometrium after subcutaneous injection in NOD-SCID mice. Briefly, SP cells of human endometrium from epithelial and stromal compartments display genotypic, phenotypic and functional features of SSC. PMID- 20585576 TI - OsPIE1, the rice ortholog of Arabidopsis PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1, is essential for embryo development. AB - BACKGROUND: The SWR1 complex is important for the deposition of histone variant H2A.Z into chromatin necessary to robustly regulate gene expression during growth and development. In Arabidopsis thaliana, the catalytic subunit of the SWR1-like complex, encoded by PIE1 (PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1), has been shown to function in multiple developmental processes including flowering time pathways and petal number regulation. However, the function of the PIE1 orthologs in monocots remains unknown. METHODOLOGY/FINDINGS: We report the identification of the rice (Oryza sativa) ortholog, OsPIE1. Although OsPIE1 does not exhibit a conserved exon/intron structure as Arabidopsis PIE1, its encoded protein is highly similar to PIE1, sharing 53.9% amino acid sequence identity. OsPIE1 also has a very similar expression pattern as PIE1. Furthermore, transgenic expression of OsPIE1 completely rescued both early flowering and extra petal number phenotypes of the Arabidopsis pie1-2 mutant. However, homozygous T-DNA insertional mutants of OsPIE1 in rice were embryonically lethal, in contrast to the viable mutants in the orthologous genes for yeast, Drosophila and Arabidopsis (Swr1, DOMINO and PIE1, respectively). CONCLUSIONS/SIGNIFICANCE: Taken together, our results suggest that OsPIE1 is the rice ortholog of Arabidopsis PIE1 and plays an essential role in rice embryo development. PMID- 20585577 TI - The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity. AB - BACKGROUND: Breast cancer is a remarkably heterogeneous disease. Luminal, basal like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21(Cip1) correlated with senescence in these cell lines. p21(Cip1) knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24 /ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. CONCLUSIONS/SIGNIFICANCE: Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential. PMID- 20585578 TI - The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men. AB - The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R) and the interleukin 6 (IL6) haplotypes modulates the risk of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R) were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S), indicates the presence of a synergy (S>1) or of an antagonism (S<1). None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI) of 1.58 (1.05-2.41) (p = 0.02) in the crude and an OR of 1.72 (1.11-2.67) (p = 0.01) in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI) of 2.24 (1.27-3.95) (p = 0.005) and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI) of 1.56 (1.02-2.37) (p = 0.03) and S of 1.66 (0.89-31). In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI. PMID- 20585579 TI - The terminal immunoglobulin-like repeats of LigA and LigB of Leptospira enhance their binding to gelatin binding domain of fibronectin and host cells. AB - Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (K(D) = 1.91+/-0.40 microM). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction. PMID- 20585580 TI - GPS-SNO: computational prediction of protein S-nitrosylation sites with a modified GPS algorithm. AB - As one of the most important and ubiquitous post-translational modifications (PTMs) of proteins, S-nitrosylation plays important roles in a variety of biological processes, including the regulation of cellular dynamics and plasticity. Identification of S-nitrosylated substrates with their exact sites is crucial for understanding the molecular mechanisms of S-nitrosylation. In contrast with labor-intensive and time-consuming experimental approaches, prediction of S-nitrosylation sites using computational methods could provide convenience and increased speed. In this work, we developed a novel software of GPS-SNO 1.0 for the prediction of S-nitrosylation sites. We greatly improved our previously developed algorithm and released the GPS 3.0 algorithm for GPS-SNO. By comparison, the prediction performance of GPS 3.0 algorithm was better than other methods, with an accuracy of 75.80%, a sensitivity of 53.57% and a specificity of 80.14%. As an application of GPS-SNO 1.0, we predicted putative S-nitrosylation sites for hundreds of potentially S-nitrosylated substrates for which the exact S nitrosylation sites had not been experimentally determined. In this regard, GPS SNO 1.0 should prove to be a useful tool for experimentalists. The online service and local packages of GPS-SNO were implemented in JAVA and are freely available at: http://sno.biocuckoo.org/. PMID- 20585581 TI - Androgen excess produces systemic oxidative stress and predisposes to beta-cell failure in female mice. AB - In women, excess production of the male hormone, testosterone (T), is accompanied by insulin resistance. However, hyperandrogenemia is also associated with beta cell dysfunction and type 2 diabetes raising the possibility that androgen receptor (AR) activation predisposes to beta-cell failure. Here, we tested the hypothesis that excess AR activation produces systemic oxidative stress thereby contributing to beta-cell failure. We used normal female mice (CF) and mice with androgen resistance by testicular feminization (Tfm). These mice were exposed to androgen excess and a beta-cell stress induced by streptozotocin (STZ). We find that following exposure to T, or the selective AR-agonist dehydrotestosterone (DHT), CF mice challenged with STZ, which are normally protected, are prone to beta-cell failure and insulin-deficient diabetes. Conversely, T-induced predisposition to beta-cell failure is abolished in Tfm mice. We do not observe any proapoptotic effect of DHT alone or in the presence of H(2)O(2) in cultured mouse and human islets. However, we observe that exposure of CF mice to T or DHT provokes systemic oxidative stress, which is eliminated in Tfm mice. This work has significance for hyperandrogenic women; excess activation of AR by testosterone may provoke systemic oxidative stress. In the presence of a prior beta-cell stress, this may predispose to beta-cell failure. PMID- 20585582 TI - The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin. AB - Intersectin-1L is a member of the Dbl homology (DH) domain guanine nucleotide exchange factors (GEF) which control Rho-family GTPase signaling. Intersectin-1L is a GEF that is specific for Cdc42. It plays an important role in endocytosis, and is regulated by several partners including the actin regulator N-WASP. Intact intersectin-1L shows low Cdc42 exchange activity, although the isolated catalytic DH domain shows high activity. This finding suggests that the molecule is autoinhibited. To investigate the mechanism of autoinhibition we have constructed a series of domain deletions. We find that the five SH3 domains of intersectin are important for autoinhibition, with the fifth domain (SH3(E)) being sufficient for the bulk of the autoinhibitory effect. This SH3 domain appears to primarily interact with the DH domain. We have determined the crystal structure of the SH3(E)-DH domain construct, which shows a domain swapped arrangement in which the SH3 from one monomer interacts with the DH domain of the other monomer. Analytical ultracentrifugation and gel filtration, however, show that under biochemical concentrations, the construct is fully monomeric. Thus we propose that the actual autoinhibited structure contains the related intramolecular SH3(E)-DH interaction. We propose a model in which this intramolecular interaction may block or distort the GTPase binding region of the DH domain. PMID- 20585583 TI - Involvement of C4 protein of beet severe curly top virus (family Geminiviridae) in virus movement. AB - BACKGROUND: Beet severe curly top virus (BSCTV) is a leafhopper transmitted geminivirus with a monopartite genome. C4 proteins encoded by geminivirus play an important role in virus/plant interaction. METHODS AND FINDINGS: To understand the function of C4 encoded by BSCTV, two BSCTV mutants were constructed by introducing termination codons in ORF C4 without affecting the amino acids encoded by overlapping ORF Rep. BSCTV mutants containing disrupted ORF C4 retained the ability to replicate in Arabidopsis protoplasts and in the agro inoculated leaf discs of N. benthamiana, suggesting C4 is not required for virus DNA replication. However, both mutants did not accumulate viral DNA in newly emerged leaves of inoculated N. benthamiana and Arabidopsis, and the inoculated plants were asymptomatic. We also showed that C4 expression in plant could help C4 deficient BSCTV mutants to move systemically. C4 was localized in the cytosol and the nucleus in both Arabidopsis protoplasts and N. benthamiana leaves and the protein appeared to bind viral DNA and ds/ssDNA nonspecifically, displaying novel DNA binding properties. CONCLUSIONS: Our results suggest that C4 protein in BSCTV is involved in symptom production and may facilitate virus movement instead of virus replication. PMID- 20585584 TI - Evolutionary trends of the pharyngeal dentition in Cypriniformes (Actinopterygii: Ostariophysi). AB - BACKGROUND: The fish order Cypriniformes is one of the most diverse ray-finned fish groups in the world with more than 3000 recognized species. Cypriniformes are characterized by a striking distribution of their dentition: namely the absence of oral teeth and presence of pharyngeal teeth on the last gill arch (fifth ceratobranchial). Despite this limited localisation, the diversity of tooth patterns in Cypriniformes is astonishing. Here we provide a further description of this diversity using X-ray microtomography and we map the resulting dental characters on a phylogenetic tree to explore evolutionary trends. RESULTS: We performed a pilot survey of dental formulae and individual tooth shapes in 34 adult species of Cypriniformes by X-ray microtomography (using either conventional X-ray machine, or synchrotron microtomography when necessary) or by dissecting. By mapping morphological results in a phylogenetic tree, it emerges that the two super-families Cobitoidea and Cyprinoidea have followed two distinct evolutionary pathways. Furthermore, our analysis supports the hypothesis of a three-row dentition as ancestral for Cyprinoidea and a general trend in tooth row reduction in most derived lineages. Yet, this general scheme must be considered with caution as several events of tooth row gain and loss have occurred during evolutionary history of Cyprinoidea. SIGNIFICANCE: Dentition diversity in Cypriniformes constitutes an excellent model to study the evolution of complex morphological structures. This morphological survey clearly advocates for extending the use of X-ray microtomography to study tooth morphology in Cypriniformes. Yet, our survey also underlines that improved knowledge of Cypriniformes life traits, such as feeding habits, is required as current knowledge is not sufficient to conclude on the link between diet and dental morphology. PMID- 20585585 TI - A femtomol range FRET biosensor reports exceedingly low levels of cell surface furin: implications for the processing of anthrax protective antigen. AB - Furin, a specialized endoproteinase, transforms proproteins into biologically active proteins. Furin function is important for normal cells and also in multiple pathologies including malignancy and anthrax. Furin is believed to cycle between the Golgi compartment and the cell surface. Processing of anthrax protective antigen-83 (PA83) by the cells is considered thus far as evidence for the presence of substantial levels of cell-surface furin. To monitor furin, we designed a cleavage-activated FRET biosensor in which the Enhanced Cyan and Yellow Fluorescent Proteins were linked by the peptide sequence SNSRKKR / STSAGP derived from anthrax PA83. Both because of the sensitivity and selectivity of the anthrax sequence to furin proteolysis and the FRET-based detection, the biosensor recorded the femtomolar levels of furin in the in vitro reactions and cell-based assays. Using the biosensor that was cell-impermeable because of its size and also by other relevant methods, we determined that exceedingly low levels, if any, of cell-surface furin are present in the intact cells and in the cells with the enforced furin overexpression. This observation was in a sharp contrast with the existing concepts about the furin presentation on cell surfaces and anthrax disease mechanism. We next demonstrated using cell-based tests that PA83, in fact, was processed by furin in the extracellular milieu and that only then the resulting PA63 bound the anthrax toxin cell-surface receptors. We also determined that the biosensor, but not the conventional peptide substrates, allowed continuous monitoring of furin activity in cancer cell extracts. Our results suggest that there are no physiologically-relevant levels of cell-surface furin and, accordingly, that the mechanisms of anthrax should be re-investigated. In addition, the availability of the biosensor is a foundation for non-invasive monitoring of furin activity in cancer cells. Conceptually, the biosensor we developed may serve as a prototype for other proteinase-activated biosensors. PMID- 20585586 TI - Hypoxia regulates BMP4 expression in the murine spleen during the recovery from acute anemia. AB - BACKGROUND: Bone marrow erythropoiesis is primarily homeostatic, producing new erythrocytes at a constant rate. However at times of acute anemia, new erythrocytes must be rapidly produced much faster than bone marrow steady state erythropoiesis. At these times stress erythropoiesis predominates. Stress erythropoiesis occurs in the fetal liver during embryogenesis and in the adult spleen and liver. In adult mice, stress erythropoiesis utilizes a specialized population of stress erythroid progenitors that are resident in the spleen. In response to acute anemia, these progenitors rapidly expand and differentiate in response to three signals, BMP4, SCF and hypoxia. In absence of acute anemic stress, two of these signals, BMP4 and hypoxia, are not present and the pathway is not active. The initiating event in the activation of this pathway is the up regulation of BMP4 expression in the spleen. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we analyze the regulation of BMP4 expression in the spleen by hypoxia. Using stromal cell lines, we establish a role for hypoxia transcription factor HIFs (Hypoxia Inducible Factors) in the transcription of BMP4. We identified putative Hypoxia Responsive Elements (HREs) in the BMP4 gene using bioinformatics. Analysis of these elements showed that in vivo, Hif2alpha binds two cis regulatory sites in the BMP4 gene, which regulate BMP4 expression during the recovery from acute anemia. CONCLUSIONS AND SIGNIFICANCE: These data show that hypoxia plays a key role in initiating the BMP4 dependent stress erythropoiesis pathway by regulating BMP4 expression. PMID- 20585591 TI - Phonological Spelling and Reading Deficits in Children with Spelling Disabilities. AB - Spelling errors in the Wide Range Achievement Test were analyzed for 77 pairs of children, each of which included one older child with spelling disability (SD) and one spelling-level-matched younger child with normal spelling ability from the Colorado Learning Disabilities Research Center database. Spelling error analysis consisted of a percent graphotactic-accuracy (GA) score based on syllable position and existence in English, and a phonological accuracy score (PA). The SD group scored significantly worse in the PA measure, and non significantly better than controls on the GA measure. The group by measure interaction was significant. Spelling matched pairs had very similar scores for word recognition and orthographic coding, but the SD group exhibited significant deficits in reading measures of phonological decoding and in language measures of phonological awareness. PMID- 20585587 TI - Class II transactivator (CIITA) enhances cytoplasmic processing of HIV-1 Pr55Gag. AB - BACKGROUND: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160(gag-pol) (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA expressing cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post transcriptional, cytoplasmic function for a well-known transactivator. PMID- 20585592 TI - Contribution of mycosporine-like amino acids and colored dissolved and particulate matter to sea ice optical properties and ultraviolet attenuation. AB - In the Baltic Sea ice, the spectral absorption coefficients for particulate matter (PM) were about two times higher at ultraviolet wavelengths than at photosynthetically available radiation (PAR) wavelengths. PM absorption spectra included significant absorption by mycosporine-like amino acids (MAAs) between 320 and 345 nm. In the surface ice layer, the concentration of MAAs (1.37 MUg L( 1)) was similar to that of chlorophyll a, resulting in a MAAs-to-chlorophyll a ratio as high as 0.65. Ultraviolet radiation (UVR) intensity and the ratio of UVR to PAR had a strong relationship with MAAs concentration (R(2) = 0.97, n = 3) in the ice. In the surface ice layer, PM and especially MAAs dominated the absorption (absorption coefficient at 325 nm: 0.73 m(-1)). In the columnar ice layers, colored dissolved organic matter was the most significant absorber in the UVR (< 380 nm) (absorption coefficient at 325 nm: 1.5 m(-1)). Our measurements and modeling of UVR and PAR in Baltic Sea ice show that organic matter, both particulate and dissolved, influences the optical properties of sea ice and strongly modifies the UVR exposure of biological communities in and under snow free sea ice. PMID- 20585593 TI - Hydrodynamic trap for single particles and cells. AB - Trapping and manipulation of microscale and nanoscale particles is demonstrated using the sole action of hydrodynamic forces. We developed an automated particle trap based on a stagnation point flow generated in a microfluidic device. The hydrodynamic trap enables confinement and manipulation of single particles in low viscosity (1-10 cP) aqueous solution. Using this method, we trapped microscale and nanoscale particles (100 nm-15 mum) for long time scales (minutes to hours). We demonstrate particle confinement to within 1 mum of the trap center, corresponding to a trap stiffness of approximately 10(-5)-10(-4) pNnm. PMID- 20585594 TI - One Small Step for Man, Two Large Steps for HAND. PMID- 20585595 TI - The desmosomal plaque proteins of the plakophilin family. AB - Three related proteins of the plakophilin family (PKP1_3) have been identified as junctional proteins that are essential for the formation and stabilization of desmosomal cell contacts. Failure of PKP expression can have fatal effects on desmosomal adhesion, leading to abnormal tissue and organ development. Thus, loss of functional PKP 1 in humans leads to ectodermal dysplasia/skin fragility (EDSF) syndrome, a genodermatosis with severe blistering of the epidermis as well as abnormal keratinocytes differentiation. Mutations in the human PKP 2 gene have been linked to severe heart abnormalities that lead to arrhythmogenic right ventricular cardiomyopathy (ARVC). In the past few years it has been shown that junctional adhesion is not the only function of PKPs. These proteins have been implicated in cell signaling, organization of the cytoskeleton, and control of protein biosynthesis under specific cellular circumstances. Clearly, PKPs are more than just cell adhesion proteins. In this paper we will give an overview of our current knowledge on the very distinct roles of plakophilins in the cell. PMID- 20585596 TI - Experimental human cell and tissue models of pemphigus. AB - Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model. PMID- 20585597 TI - Vitiligo after diphencyprone for alopecia areata. AB - The topical immunotherapy is used to treat alopecia areata and recalcitrant warts since the 1970s. Diphencyprone is a contact sensitizer used to treat dermatological conditions resulting from as altered immunological state, such as extensive alopecia areata, being partially effective and safe. Side effects include local eczema with blistering, regional lymphadenopathy and contact urticaria. Rare adverse effects include an erythema multiforme-like reaction, hyperpigmenttion, hypopigmentation, and vitiligo. We report a 30-year-old, Brazilian male who developed vitiligo lesions following DPCP therapy for alopecia areata. PMID- 20585598 TI - A new perspective on intercalated disc organization: implications for heart disease. AB - Adherens junctions and desmosomes are intercellular adhesive junctions and essential for the morphogenesis, differentiation, and maintenance of tissues that are subjected to high mechanical stress, including heart and skin. The different junction complexes are organized at the termini of the cardiomyocyte called the intercalated disc. Disruption of adhesive integrity via mutations in genes encoding desmosomal proteins causes an inherited heart disease, arrhythmogenic right ventricular cardiomyopathy (ARVC). Besides plakoglobin, which is shared by adherens junctions and desmosomes, other desmosomal components, desmoglein-2, desmocollin-2, plakophilin-2, and desmoplakin are also present in ultrastructurally defined fascia adherens junctions of heart muscle, but not other tissues. This mixed-type of junctional structure is termed hybrid adhering junction or area composita. Desmosomal plakophilin-2 directly interacts with adherens junction protein alphaT-catenin, providing a new molecular link between the cadherin-catenin complex and desmosome. The area composita only exists in the cardiac intercalated disc of mammalian species suggesting that it evolved to strengthen mechanical coupling in the heart of higher vertebrates. The cross-talk among different junctions and their implication in the pathogenesis of ARVC are discussed in this review. PMID- 20585599 TI - Subcutaneous Sarcoidosis during Pegylated Interferon Alfa and Ribavirin Treatment for Chronic Hepatitis C. AB - Interferon is used to treat hepatitis C virus infection and its cutaneous side effects are well known. Recently, interferon-induced sarcoidosis has been reported. We report a new case of sarcoidosis during pegylated interferon alfa and ribavirin treatment with an unusual presentation in a woman with previous episodes of erythema nodusum and nodular vasculitis related to HCV. PMID- 20585600 TI - Clinical presentation of a patient with localized acquired cutis laxa of abdomen: a case report. AB - Background. Cutis laxa (CL) is a rare disorder of elastic tissue characterized by loose, sagging skin with reduced elasticity, and resilience without resulting scarring. CL may be inherited as a dominant, recessive, or X-linked recessive disease, or acquired. The heritable forms of CL predominantly begin at birth, but it may be delayed until puberty or age of 30 years with extracutaneous manifestations including pulmonary emphysema, umbilical and inguinal hernias, and gastrointestinal and vesicourinary tract diverticuli. An acquired form of the disease occurs in adults with no evidence of internal organ involvement. Objective. The aim of this case report was to present our patient suffering from CL, and to evaluate clinical presentation, diagnostic and therapeutic difficulties in this rare condition. Case Report. A 30-year-old female patient was admitted to our Hospital due to localized loose and sagging skin of abdomen, induced by prior cesarean section 6 years ago. CL has been diagnosed based on the clinical picture and pathohistological appearance. Conclusion. Reconstructive surgery provides a dramatic cosmetic improvement with significant psychosocial benefit. Repeated surgical procedures may be required to correct the lax skin, which worsens with age. PMID- 20585601 TI - Stress as a possible mechanism in melanoma progression. AB - The incidence of melanoma, the most aggressive type of cutaneous malignant tumor, is currently on the rise. Treatment in advanced stages is still unsuccessful compared with other malignant tumors, thus it is important to indentify the key mechanisms responsible for melanoma progression and metastasis. Genetic and molecular components, in particular, that are up- or downregulated in melanoma cells, affect the invasive potential of melanoma. Another possible important cofactor highlighted by recent studies is chronic stress, involving environmental and psychological factors, which can be an important cofactor in not only cancer progression in general but also in melanoma spreading. The negative effects of chronic stress have been evaluated epidemiologically in patients with breast and prostate cancer. In particular, the effects of stress mediators, namely, catecholamines have been studied on various human malignancies, including melanoma and have highlighted a significant increase of progression-related molecules. As such, this could be the starting point for a new approach in the treatment of advanced melanoma, in which the negative effects of stress are reduced or blocked. PMID- 20585602 TI - Mouse models for blistering skin disorders. AB - Genetically engineered mice have been essential tools for elucidating the pathological mechanisms underlying human diseases. In the case of diseases caused by impaired desmosome function, mouse models have helped to establish causal links between mutations and disease phenotypes. This review focuses on mice that lack the desmosomal cadherins desmoglein 3 or desmocollin 3 in stratified epithelia. A comparison of the phenotypes observed in these mouse lines is provided and the relationship between the mutant mouse phenotypes and human diseases, in particular pemphigus vulgaris, is discussed. Furthermore, we will discuss the advantages and potential limitations of genetically engineered mouse lines in our ongoing quest to understand blistering skin diseases. PMID- 20585603 TI - Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma. AB - Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity. PMID- 20585604 TI - A hypothesis concerning a potential involvement of ceramide in apoptosis and acantholysis induced by pemphigus autoantibodies. AB - Autoimmune diseases affect more than 50 million Americans, resulting in significant healthcare costs. Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF) is an autoimmune skin disease localized to specific geographic loci. EPF, and the related diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are characterized by skin lesions and autoantibodies to molecules found on epidermal keratinocytes. A variant of EPF in patients from El Bagre, Colombia, South America, has recently been reported to be distinct from previously described loci in Brazil and Tunisia epidemiologically and immunologically. As in PF and EPF, El Bagre EPF patients exhibit autoantibodies towards desmoglein-1, a cell adhesion molecule critical for maintaining epidermal integrity. An association of El Bagre EPF with sun exposure has been detected, and ultraviolet irradiation also exacerbates symptoms in PV, PF and EPF. Our hypothesis is that: (1) the autoantibodies generate pathology through an alteration in ceramide metabolism in targeted keratinocytes, resulting in apoptosis and/or cell death and acantholysis, but only when the cell's ability to metabolize ceramide is exceeded, and (2) apoptosis in response to this altered ceramide metabolism is initiated and/or exacerbated by other agents that increase ceramide levels, such as cytokines, ultraviolet irradiation, and senescence. PMID- 20585605 TI - Polychlorinated biphenyls (PCBs) enhance metastatic properties of breast cancer cells by activating Rho-associated kinase (ROCK). AB - BACKGROUND: Polychlorinated biphenyls (PCBs) are a family of structurally related chlorinated aromatic hydrocarbons. Numerous studies have documented a wide spectrum of biological effects of PCBs on human health, such as immunotoxicity, neurotoxicity, estrogenic or antiestrogenic activity, and carcinogenesis. The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo, animal and epidemiologic studies. A number of investigations indicated that higher levels of PCBs in mammary tissues or sera correlated to breast cancer risk, and PCBs might be implicated in advancing breast cancer progression. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we for the first time report that PCBs greatly promote the ROCK activity and therefore increase cell motility for both non-metastatic and metastatic human breast cancer cells in vitro. In the in vivo study, PCBs significantly advance disease progression, leading to enhanced capability of metastatic breast cancer cells to metastasize to bone, lung and liver. Additionally, PCBs robustly induce the production of intracellular reactive oxygen species (ROS) in breast cancer cells; ROS mechanistically elevate ROCK activity. CONCLUSIONS/SIGNIFICANCE: PCBs enhance the metastatic propensity of breast cancer cells by activating the ROCK signaling, which is dependent on ROS induced by PCBs. Inhibition of ROCK may stand for a unique way to restrain metastases in breast cancer upon PCB exposure. PMID- 20585606 TI - The effect of visual cues on auditory stream segregation in musicians and non musicians. AB - BACKGROUND: The ability to separate two interleaved melodies is an important factor in music appreciation. This ability is greatly reduced in people with hearing impairment, contributing to difficulties in music appreciation. The aim of this study was to assess whether visual cues, musical training or musical context could have an effect on this ability, and potentially improve music appreciation for the hearing impaired. METHODS: Musicians (N = 18) and non musicians (N = 19) were asked to rate the difficulty of segregating a four-note repeating melody from interleaved random distracter notes. Visual cues were provided on half the blocks, and two musical contexts were tested, with the overlap between melody and distracter notes either gradually increasing or decreasing. CONCLUSIONS: Visual cues, musical training, and musical context all affected the difficulty of extracting the melody from a background of interleaved random distracter notes. Visual cues were effective in reducing the difficulty of segregating the melody from distracter notes, even in individuals with no musical training. These results are consistent with theories that indicate an important role for central (top-down) processes in auditory streaming mechanisms, and suggest that visual cues may help the hearing-impaired enjoy music. PMID- 20585610 TI - 2010 ISCB Overton Prize Awarded to Steven E. Brenner. PMID- 20585611 TI - Computational prediction and experimental assessment of secreted/surface proteins from Mycobacterium tuberculosis H37Rv. AB - The mycobacterial cell envelope has been implicated in the pathogenicity of tuberculosis and therefore has been a prime target for the identification and characterization of surface proteins with potential application in drug and vaccine development. In this study, the genome of Mycobacterium tuberculosis H37Rv was screened using Machine Learning tools that included feature-based predictors, general localizers and transmembrane topology predictors to identify proteins that are potentially secreted to the surface of M. tuberculosis, or to the extracellular milieu through different secretory pathways. The subcellular localization of a set of 8 hypothetically secreted/surface candidate proteins was experimentally assessed by cellular fractionation and immunoelectron microscopy (IEM) to determine the reliability of the computational methodology proposed here, using 4 secreted/surface proteins with experimental confirmation as positive controls and 2 cytoplasmic proteins as negative controls. Subcellular fractionation and IEM studies provided evidence that the candidate proteins Rv0403c, Rv3630, Rv1022, Rv0835, Rv0361 and Rv0178 are secreted either to the mycobacterial surface or to the extracellular milieu. Surface localization was also confirmed for the positive controls, whereas negative controls were located on the cytoplasm. Based on statistical learning methods, we obtained computational subcellular localization predictions that were experimentally assessed and allowed us to construct a computational protocol with experimental support that allowed us to identify a new set of secreted/surface proteins as potential vaccine candidates. PMID- 20585612 TI - Slope-based stochastic resonance: how noise enables phasic neurons to encode slow signals. AB - Fundamental properties of phasic firing neurons are usually characterized in a noise-free condition. In the absence of noise, phasic neurons exhibit Class 3 excitability, which is a lack of repetitive firing to steady current injections. For time-varying inputs, phasic neurons are band-pass filters or slope detectors, because they do not respond to inputs containing exclusively low frequencies or shallow slopes. However, we show that in noisy conditions, response properties of phasic neuron models are distinctly altered. Noise enables a phasic model to encode low-frequency inputs that are outside of the response range of the associated deterministic model. Interestingly, this seemingly stochastic resonance (SR) like effect differs significantly from the classical SR behavior of spiking systems in both the signal-to-noise ratio and the temporal response pattern. Instead of being most sensitive to the peak of a subthreshold signal, as is typical in a classical SR system, phasic models are most sensitive to the signal's rising and falling phases where the slopes are steep. This finding is consistent with the fact that there is not an absolute input threshold in terms of amplitude; rather, a response threshold is more properly defined as a stimulus slope/frequency. We call the encoding of low-frequency signals with noise by phasic models a slope-based SR, because noise can lower or diminish the slope threshold for ramp stimuli. We demonstrate here similar behaviors in three mechanistic models with Class 3 excitability in the presence of slow-varying noise and we suggest that the slope-based SR is a fundamental behavior associated with general phasic properties rather than with a particular biological mechanism. PMID- 20585613 TI - Mammalian sleep dynamics: how diverse features arise from a common physiological framework. AB - Mammalian sleep varies widely, ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans. In humans, rats, mice and cats, sleep patterns are orchestrated by homeostatic and circadian drives to the sleep-wake switch, but it is not known whether this system is ubiquitous among mammals. Here, changes of just two parameters in a recent quantitative model of this switch are shown to reproduce typical sleep patterns for 17 species across 7 orders. Furthermore, the parameter variations are found to be consistent with the assumptions that homeostatic production and clearance scale as brain volume and surface area, respectively. Modeling an additional inhibitory connection between sleep-active neuronal populations on opposite sides of the brain generates unihemispheric sleep, providing a testable hypothetical mechanism for this poorly understood phenomenon. Neuromodulation of this connection alone is shown to account for the ability of fur seals to transition between bihemispheric sleep on land and unihemispheric sleep in water. Determining what aspects of mammalian sleep patterns can be explained within a single framework, and are thus universal, is essential to understanding the evolution and function of mammalian sleep. This is the first demonstration of a single model reproducing sleep patterns for multiple different species. These wide-ranging findings suggest that the core physiological mechanisms controlling sleep are common to many mammalian orders, with slight evolutionary modifications accounting for interspecies differences. PMID- 20585615 TI - Consent and internet-enabled human genomics. PMID- 20585614 TI - Multiscale coarse-graining of the protein energy landscape. AB - A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states. PMID- 20585616 TI - Drosophila genome-wide RNAi screen identifies multiple regulators of HIF dependent transcription in hypoxia. AB - Hypoxia-inducible factors (HIFs) are a family of evolutionary conserved alpha beta heterodimeric transcription factors that induce a wide range of genes in response to low oxygen tension. Molecular mechanisms that mediate oxygen dependent HIF regulation operate at the level of the alpha subunit, controlling protein stability, subcellular localization, and transcriptional coactivator recruitment. We have conducted an unbiased genome-wide RNA interference (RNAi) screen in Drosophila cells aimed to the identification of genes required for HIF activity. After 3 rounds of selection, 30 genes emerged as critical HIF regulators in hypoxia, most of which had not been previously associated with HIF biology. The list of genes includes components of chromatin remodeling complexes, transcription elongation factors, and translational regulators. One remarkable hit was the argonaute 1 (ago1) gene, a central element of the microRNA (miRNA) translational silencing machinery. Further studies confirmed the physiological role of the miRNA machinery in HIF-dependent transcription. This study reveals the occurrence of novel mechanisms of HIF regulation, which might contribute to developing novel strategies for therapeutic intervention of HIF-related pathologies, including heart attack, cancer, and stroke. PMID- 20585617 TI - Brca2 and Trp53 deficiency cooperate in the progression of mouse prostate tumourigenesis. AB - Epidemiological studies have shown that one of the strongest risk factors for prostate cancer is a family history of the disease, suggesting that inherited factors play a major role in prostate cancer susceptibility. Germline mutations in BRCA2 predispose to breast and ovarian cancer with its predominant tumour suppressor function thought to be the repair of DNA double-strand breaks. BRCA2 has also been implicated in prostate cancer etiology, but it is unclear the impact that mutations in this gene have on prostate tumourigenesis. Here we have undertaken a genetic analysis in the mouse to determine the role of Brca2 in the adult prostate. We show that deletion of Brca2 specifically in prostate epithelia results in focal hyperplasia and low-grade prostate intraepithelial neoplasia (PIN) in animals over 12 months of age. Simultaneous deletion of Brca2 and the tumour suppressor Trp53 in prostate epithelia gave rise to focal hyperplasia and atypical cells at 6 months, leading to high-grade PIN in animals from 12 months. Epithelial cells in these lesions show an increase in DNA damage and have higher levels of proliferation, but also elevated apoptosis. Castration of Brca2;Trp53 mutant animals led to regression of PIN lesions, but atypical cells persisted that continued to proliferate and express nuclear androgen receptor. This study provides evidence that Brca2 can act as a tumour suppressor in the prostate, and the model we describe should prove useful in the development of new therapeutic approaches. PMID- 20585618 TI - Endoreplication controls cell fate maintenance. AB - Cell-fate specification is typically thought to precede and determine cell-cycle regulation during differentiation. Here we show that endoreplication, also known as endoreduplication, a specialized cell-cycle variant often associated with cell differentiation but also frequently occurring in malignant cells, plays a role in maintaining cell fate. For our study we have used Arabidopsis trichomes as a model system and have manipulated endoreplication levels via mutants of cell cycle regulators and overexpression of cell-cycle inhibitors under a trichome specific promoter. Strikingly, a reduction of endoreplication resulted in reduced trichome numbers and caused trichomes to lose their identity. Live observations of young Arabidopsis leaves revealed that dedifferentiating trichomes re-entered mitosis and were re-integrated into the epidermal pavement-cell layer, acquiring the typical characteristics of the surrounding epidermal cells. Conversely, when we promoted endoreplication in glabrous patterning mutants, trichome fate could be restored, demonstrating that endoreplication is an important determinant of cell identity. Our data lead to a new model of cell-fate control and tissue integrity during development by revealing a cell-fate quality control system at the tissue level. PMID- 20585619 TI - Plato's cave algorithm: inferring functional signaling networks from early gene expression shadows. AB - Improving the ability to reverse engineer biochemical networks is a major goal of systems biology. Lesions in signaling networks lead to alterations in gene expression, which in principle should allow network reconstruction. However, the information about the activity levels of signaling proteins conveyed in overall gene expression is limited by the complexity of gene expression dynamics and of regulatory network topology. Two observations provide the basis for overcoming this limitation: a. genes induced without de-novo protein synthesis (early genes) show a linear accumulation of product in the first hour after the change in the cell's state; b. The signaling components in the network largely function in the linear range of their stimulus-response curves. Therefore, unlike most genes or most time points, expression profiles of early genes at an early time point provide direct biochemical assays that represent the activity levels of upstream signaling components. Such expression data provide the basis for an efficient algorithm (Plato's Cave algorithm; PLACA) to reverse engineer functional signaling networks. Unlike conventional reverse engineering algorithms that use steady state values, PLACA uses stimulated early gene expression measurements associated with systematic perturbations of signaling components, without measuring the signaling components themselves. Besides the reverse engineered network, PLACA also identifies the genes detecting the functional interaction, thereby facilitating validation of the predicted functional network. Using simulated datasets, the algorithm is shown to be robust to experimental noise. Using experimental data obtained from gonadotropes, PLACA reverse engineered the interaction network of six perturbed signaling components. The network recapitulated many known interactions and identified novel functional interactions that were validated by further experiment. PLACA uses the results of experiments that are feasible for any signaling network to predict the functional topology of the network and to identify novel relationships. PMID- 20585620 TI - Atomic-resolution simulations predict a transition state for vesicle fusion defined by contact of a few lipid tails. AB - Membrane fusion is essential to both cellular vesicle trafficking and infection by enveloped viruses. While the fusion protein assemblies that catalyze fusion are readily identifiable, the specific activities of the proteins involved and nature of the membrane changes they induce remain unknown. Here, we use many atomic-resolution simulations of vesicle fusion to examine the molecular mechanisms for fusion in detail. We employ committor analysis for these million atom vesicle fusion simulations to identify a transition state for fusion stalk formation. In our simulations, this transition state occurs when the bulk properties of each lipid bilayer remain in a lamellar state but a few hydrophobic tails bulge into the hydrophilic interface layer and make contact to nucleate a stalk. Additional simulations of influenza fusion peptides in lipid bilayers show that the peptides promote similar local protrusion of lipid tails. Comparing these two sets of simulations, we obtain a common set of structural changes between the transition state for stalk formation and the local environment of peptides known to catalyze fusion. Our results thus suggest that the specific molecular properties of individual lipids are highly important to vesicle fusion and yield an explicit structural model that could help explain the mechanism of catalysis by fusion proteins. PMID- 20585621 TI - Contributions of Mamu-A*01 status and TRIM5 allele expression, but not CCL3L copy number variation, to the control of SIVmac251 replication in Indian-origin rhesus monkeys. AB - CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis. PMID- 20585622 TI - Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus. AB - The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for approximately 16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession. PMID- 20585623 TI - Amplification of a cytochrome P450 gene is associated with resistance to neonicotinoid insecticides in the aphid Myzus persicae. AB - The aphid Myzus persicae is a globally significant crop pest that has evolved high levels of resistance to almost all classes of insecticide. To date, the neonicotinoids, an economically important class of insecticides that target nicotinic acetylcholine receptors (nAChRs), have remained an effective control measure; however, recent reports of resistance in M. persicae represent a threat to the long-term efficacy of this chemical class. In this study, the mechanisms underlying resistance to the neonicotinoid insecticides were investigated using biological, biochemical, and genomic approaches. Bioassays on a resistant M. persicae clone (5191A) suggested that P450-mediated detoxification plays a primary role in resistance, although additional mechanism(s) may also contribute. Microarray analysis, using an array populated with probes corresponding to all known detoxification genes in M. persicae, revealed constitutive over-expression (22-fold) of a single P450 gene (CYP6CY3); and quantitative PCR showed that the over-expression is due, at least in part, to gene amplification. This is the first report of a P450 gene amplification event associated with insecticide resistance in an agriculturally important insect pest. The microarray analysis also showed over-expression of several gene sequences that encode cuticular proteins (2-16-fold), and artificial feeding assays and in vivo penetration assays using radiolabeled insecticide provided direct evidence of a role for reduced cuticular penetration in neonicotinoid resistance. Conversely, receptor radioligand binding studies and nucleotide sequencing of nAChR subunit genes suggest that target-site changes are unlikely to contribute to resistance to neonicotinoid insecticides in M. persicae. PMID- 20585624 TI - A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy. AB - Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l) gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease. PMID- 20585625 TI - Non-redundant selector and growth-promoting functions of two sister genes, buttonhead and Sp1, in Drosophila leg development. AB - The radically distinct morphologies of arthropod and tetrapod legs argue that these appendages do not share a common evolutionary origin. Yet, despite dramatic differences in morphology, it has been known for some time that transcription factors encoded by the Distalless (Dll)/Dlx gene family play a critical role in the development of both structures. Here we show that a second transcription factor family encoded by the Sp8 gene family, previously implicated in vertebrate limb development, also plays an early and fundamental role in arthropod leg development. By simultaneously removing the function of two Sp8 orthologs, buttonhead (btd) and Sp1, during Drosophila embryogenesis, we find that adult leg development is completely abolished. Remarkably, in the absence of these factors, transformations from ventral to dorsal appendage identities are observed, suggesting that adult dorsal fates become derepressed when ventral fates are eliminated. Further, we show that Sp1 plays a much more important role in ventral appendage specification than btd and that Sp1 lies genetically upstream of Dll. In addition to these selector-like gene functions, Sp1 and btd are also required during larval stages for the growth of the leg. Vertebrate Sp8 can rescue many of the functions of the Drosophila genes, arguing that these activities have been conserved, despite more than 500 million years of independent evolution. These observations suggest that an ancient Sp8/Dlx gene cassette was used in an early metazoan for primitive limb-like outgrowths and that this cassette was co-opted multiple times for appendage formation in multiple animal phyla. PMID- 20585626 TI - Identification of a functional genetic variant at 16q12.1 for breast cancer risk: results from the Asia Breast Cancer Consortium. AB - Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures. PMID- 20585627 TI - Web-based, participant-driven studies yield novel genetic associations for common traits. AB - Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R) for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1), freckling (rs2153271, in BNC2), the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7), and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2) illustrates the power of the approach. PMID- 20585628 TI - Tandem E2F binding sites in the promoter of the p107 cell cycle regulator control p107 expression and its cellular functions. AB - The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells. PMID- 20585631 TI - Entry and fusion of emerging paramyxoviruses. PMID- 20585630 TI - EspA acts as a critical mediator of ESX1-dependent virulence in Mycobacterium tuberculosis by affecting bacterial cell wall integrity. AB - Mycobacterium tuberculosis (Mtb) requires the ESX1 specialized protein secretion system for virulence, for triggering cytosolic immune surveillance pathways, and for priming an optimal CD8+ T cell response. This suggests that ESX1 might act primarily by destabilizing the phagosomal membrane that surrounds the bacterium. However, identifying the primary function of the ESX1 system has been difficult because deletion of any substrate inhibits the secretion of all known substrates, thereby abolishing all ESX1 activity. Here we demonstrate that the ESX1 substrate EspA forms a disulfide bonded homodimer after secretion. By disrupting EspA disulfide bond formation, we have dissociated virulence from other known ESX1 mediated activities. Inhibition of EspA disulfide bond formation does not inhibit ESX1 secretion, ESX1-dependent stimulation of the cytosolic pattern receptors in the infected macrophage or the ability of Mtb to prime an adaptive immune response to ESX1 substrates. However, blocking EspA disulfide bond formation severely attenuates the ability of Mtb to survive and cause disease in mice. Strikingly, we show that inhibition of EspA disulfide bond formation also significantly compromises the stability of the mycobacterial cell wall, as does deletion of the ESX1 locus or individual components of the ESX1 system. Thus, we demonstrate that EspA is a major determinant of ESX1-mediated virulence independent of its function in ESX1 secretion. We propose that ESX1 and EspA play central roles in the virulence of Mtb in vivo because they alter the integrity of the mycobacterial cell wall. PMID- 20585629 TI - A viral microRNA down-regulates multiple cell cycle genes through mRNA 5'UTRs. AB - Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3' untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5'UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5'UTRs. PMID- 20585632 TI - Protein expression redirects vesicular stomatitis virus RNA synthesis to cytoplasmic inclusions. AB - Positive-strand and double-strand RNA viruses typically compartmentalize their replication machinery in infected cells. This is thought to shield viral RNA from detection by innate immune sensors and favor RNA synthesis. The picture for the non-segmented negative-strand (NNS) RNA viruses, however, is less clear. Working with vesicular stomatitis virus (VSV), a prototype of the NNS RNA viruses, we examined the location of the viral replication machinery and RNA synthesis in cells. By short-term labeling of viral RNA with 5'-bromouridine 5'-triphosphate (BrUTP), we demonstrate that primary mRNA synthesis occurs throughout the host cell cytoplasm. Protein synthesis results in the formation of inclusions that contain the viral RNA synthesis machinery and become the predominant sites of mRNA synthesis in the cell. Disruption of the microtubule network by treatment of cells with nocodazole leads to the accumulation of viral mRNA in discrete structures that decorate the surface of the inclusions. By pulse-chase analysis of the mRNA, we find that viral transcripts synthesized at the inclusions are transported away from the inclusions in a microtubule-dependent manner. Metabolic labeling of viral proteins revealed that inhibiting this transport step diminished the rate of translation. Collectively those data suggest that microtubule-dependent transport of viral mRNAs from inclusions facilitates their translation. Our experiments also show that during a VSV infection, protein synthesis is required to redirect viral RNA synthesis to intracytoplasmic inclusions. As viral RNA synthesis is initially unrestricted, we speculate that its subsequent confinement to inclusions might reflect a cellular response to infection. PMID- 20585633 TI - Paramyxovirus entry and targeted vectors for cancer therapy. PMID- 20585635 TI - Healing spinal cord injuries. PMID- 20585634 TI - Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. AB - Defensins are effectors of the innate immune response with potent antibacterial activity. Their role in antiviral immunity, particularly for non-enveloped viruses, is poorly understood. We recently found that human alpha-defensins inhibit human adenovirus (HAdV) by preventing virus uncoating and release of the endosomalytic protein VI during cell entry. Consequently, AdV remains trapped in the endosomal/lysosomal pathway rather than trafficking to the nucleus. To gain insight into the mechanism of defensin-mediated neutralization, we analyzed the specificity of the AdV-defensin interaction. Sensitivity to alpha-defensin neutralization is a common feature of HAdV species A, B1, B2, C, and E, whereas species D and F are resistant. Thousands of defensin molecules bind with low micromolar affinity to a sensitive serotype, but only a low level of binding is observed to resistant serotypes. Neutralization is dependent upon a correctly folded defensin molecule, suggesting that specific molecular interactions occur with the virion. CryoEM structural studies and protein sequence analysis led to a hypothesis that neutralization determinants are located in a region spanning the fiber and penton base proteins. This model was supported by infectivity studies using virus chimeras comprised of capsid proteins from sensitive and resistant serotypes. These findings suggest a mechanism in which defensin binding to critical sites on the AdV capsid prevents vertex removal and thereby blocks subsequent steps in uncoating that are required for release of protein VI and endosomalysis during infection. In addition to informing the mechanism of defensin-mediated neutralization of a non-enveloped virus, these studies provide insight into the mechanism of AdV uncoating and suggest new strategies to disrupt this process and inhibit infection. PMID- 20585636 TI - A fiber-optic fluorescence microscope using a consumer-grade digital camera for in vivo cellular imaging. AB - BACKGROUND: Early detection is an essential component of cancer management. Unfortunately, visual examination can often be unreliable, and many settings lack the financial capital and infrastructure to operate PET, CT, and MRI systems. Moreover, the infrastructure and expense associated with surgical biopsy and microscopy are a challenge to establishing cancer screening/early detection programs in low-resource settings. Improvements in performance and declining costs have led to the availability of optoelectronic components, which can be used to develop low-cost diagnostic imaging devices for use at the point-of-care. Here, we demonstrate a fiber-optic fluorescence microscope using a consumer-grade camera for in vivo cellular imaging. METHODS: The fiber-optic fluorescence microscope includes an LED light, an objective lens, a fiber-optic bundle, and a consumer-grade digital camera. The system was used to image an oral cancer cell line labeled with 0.01% proflavine. A human tissue specimen was imaged following surgical resection, enabling dysplastic and cancerous regions to be evaluated. The oral mucosa of a healthy human subject was imaged in vivo, following topical application of 0.01% proflavine. FINDINGS: The fiber-optic microscope resolved individual nuclei in all specimens and tissues imaged. This capability allowed qualitative and quantitative differences between normal and precancerous or cancerous tissues to be identified. The optical efficiency of the system permitted imaging of the human oral mucosa in real time. CONCLUSION: Our results indicate this device as a useful tool to assist in the identification of early neoplastic changes in epithelial tissues. This portable, inexpensive unit may be particularly appropriate for use at the point-of-care in low-resource settings. PMID- 20585637 TI - Model-based evaluation of highly and low pathogenic avian influenza dynamics in wild birds. AB - There is growing interest in avian influenza (AI) epidemiology to predict disease risk in wild and domestic birds, and prevent transmission to humans. However, understanding the epidemic dynamics of highly pathogenic (HPAI) viruses remains challenging because they have rarely been detected in wild birds. We used modeling to integrate available scientific information from laboratory and field studies, evaluate AI dynamics in individual hosts and waterfowl populations, and identify key areas for future research. We developed a Susceptible-Exposed Infectious-Recovered (SEIR) model and used published laboratory challenge studies to estimate epidemiological parameters (rate of infection, latency period, recovery and mortality rates), considering the importance of age classes, and virus pathogenicity. Infectious contact leads to infection and virus shedding within 1-2 days, followed by relatively slower period for recovery or mortality. We found a shorter infectious period for HPAI than low pathogenic (LP) AI, which may explain that HPAI has been much harder to detect than LPAI during surveillance programs. Our model predicted a rapid LPAI epidemic curve, with a median duration of infection of 50-60 days and no fatalities. In contrast, HPAI dynamics had lower prevalence and higher mortality, especially in young birds. Based on field data from LPAI studies, our model suggests to increase surveillance for HPAI in post-breeding areas, because the presence of immunologically naive young birds is predicted to cause higher HPAI prevalence and bird losses during this season. Our results indicate a better understanding of the transmission, infection, and immunity-related processes is required to refine predictions of AI risk and spread, improve surveillance for HPAI in wild birds, and develop disease control strategies to reduce potential transmission to domestic birds and/or humans. PMID- 20585639 TI - Aphid wing induction and ecological costs of alarm pheromone emission under field conditions. AB - The pea aphid, Acyrthosiphon pisum Harris, (Homoptera: Aphididae) releases the volatile sesquiterpene (E)-beta-farnesene (EBF) when attacked by a predator, triggering escape responses in the aphid colony. Recently, it was shown that this alarm pheromone also mediates the production of the winged dispersal morph under laboratory conditions. The present work tested the wing-inducing effect of EBF under field conditions. Aphid colonies were exposed to two treatments (control and EBF) and tested in two different environmental conditions (field and laboratory). As in previous experiments aphids produced higher proportion of winged morphs among their offspring when exposed to EBF in the laboratory but even under field conditions the proportion of winged offspring was higher after EBF application (6.84+/-0.98%) compared to the hexane control (1.54+/-0.25%). In the field, the proportion of adult aphids found on the plant at the end of the experiment was lower in the EBF treatment (58.1+/-5.5%) than in the control (66.9+/-4.6%), in contrast to the climate chamber test where the numbers of adult aphids found on the plant at the end of the experiment were, in both treatments, similar to the numbers put on the plant initially. Our results show that the role of EBF in aphid wing induction is also apparent under field conditions and they may indicate a potential cost of EBF emission. They also emphasize the importance of investigating the ecological role of induced defences under field conditions. PMID- 20585638 TI - Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. AB - Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations. PMID- 20585640 TI - Mapping groundwater dependent ecosystems in California. AB - BACKGROUND: Most groundwater conservation and management efforts focus on protecting groundwater for drinking water and for other human uses with little understanding or focus on the ecosystems that depend on groundwater. However, groundwater plays an integral role in sustaining certain types of aquatic, terrestrial and coastal ecosystems, and their associated landscapes. Our aim was to illuminate the connection between groundwater and surface ecosystems by identifying and mapping the distribution of groundwater dependent ecosystems (GDEs) in California. METHODOLOGY/PRINCIPAL FINDINGS: To locate where groundwater flow sustains ecosystems we identified and mapped groundwater dependent ecosystems using a GIS. We developed an index of groundwater dependency by analyzing geospatial data for three ecosystem types that depend on groundwater: (1) springs and seeps; (2) wetlands and associated vegetation alliances; and (3) stream discharge from groundwater sources (baseflow index). Each variable was summarized at the scale of a small watershed (Hydrologic Unit Code-12; mean size = 9,570 ha; n = 4,621), and then stratified and summarized to 10 regions of relative homogeneity in terms of hydrologic, ecologic and climatic conditions. We found that groundwater dependent ecosystems are widely, although unevenly, distributed across California. Although different types of GDEs are clustered more densely in certain areas of the state, watersheds with multiple types of GDEs are found in both humid (e.g. coastal) and more arid regions. Springs are most densely concentrated in the North Coast and North Lahontan, whereas groundwater dependent wetlands and associated vegetation alliances are concentrated in the North and South Lahontan and Sacramento River hydrologic regions. The percentage of land area where stream discharge is most dependent on groundwater is found in the North Coast, Sacramento River and Tulare Lake regions. GDE clusters are located at the highest percentage in the North Coast (an area of the highest annual rainfall totals), North Lahontan (an arid, high desert climate with low annual rainfall), and Sacramento River hydrologic regions. That GDEs occur in such distinct climatic and hydrologic settings reveals the widespread distribution of these ecosystems. CONCLUSIONS/SIGNIFICANCE: Protection and management of groundwater-dependent ecosystems are hindered by lack of information on their diversity, abundance and location. By developing a methodology that uses existing datasets to locate GDEs, this assessment addresses that knowledge gap. We report here on the application of this method across California, but believe the method can be expanded to regions where spatial data exist. PMID- 20585641 TI - Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog. AB - BACKGROUND: Sonic hedgehog (Shh) is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat), a member of the membrane bound O-acyl transferase (MBOAT) family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196-234) that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent K(m) and V(max) for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants. CONCLUSIONS/SIGNIFICANCE: This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases. PMID- 20585642 TI - To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling. AB - BACKGROUND: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (> or = 65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost effective option, with the closest competitor being clinical judgment (when judgment accuracy > or = 50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults. CONCLUSIONS/SIGNIFICANCE: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment. PMID- 20585643 TI - Location-specific responses to thermal stress in larvae of the reef-building coral Montastraea faveolata. AB - BACKGROUND: The potential to adapt to a changing climate depends in part upon the standing genetic variation present in wild populations. In corals, the dispersive larval phase is particularly vulnerable to the effects of environmental stress. Larval survival and response to stress during dispersal and settlement will play a key role in the persistence of coral populations. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that larval transcription profiles reflect location-specific responses to thermal stress, symbiont-free gametes from three to four colonies of the scleractinian coral Montastraea faveolata were collected from Florida and Mexico, fertilized, and raised under mean and elevated (up 1 to 2 degrees C above summer mean) temperatures. These locations have been shown to exchange larvae frequently enough to prevent significant differentiation of neutral loci. Differences among 1,310 unigenes were simultaneously characterized using custom cDNA microarrays, allowing investigation of gene expression patterns among larvae generated from wild populations under stress. Results show both conserved and location-specific variation in key processes including apoptosis, cell structuring, adhesion and development, energy and protein metabolism, and response to stress, in embryos of a reef-building coral. CONCLUSIONS/SIGNIFICANCE: These results provide first insights into location specific variation in gene expression in the face of gene flow, and support the hypothesis that coral host genomes may house adaptive potential needed to deal with changing environmental conditions. PMID- 20585644 TI - Depression, antidepressant use and mortality in later life: the Health In Men Study. AB - CONTEXT: Depression is associated with increased mortality, but it is unclear if this relationship is dose-dependent and if it can be modified by treatment with antidepressants. OBJECTIVE: To determine if (1) the association between depression and mortality is independent of other common potential causes of death in later life, (2) there is a dose-response relationship between increasing severity of depression and mortality rates, and (3) the use of antidepressant drugs reduces mortality rates. METHODS: Cohort study of 5,276 community-dwelling men aged 68-88 years living in Perth, Australia. We used the Geriatric Depression Scale 15-items (GDS-15) to ascertain the presence and severity of depression. GDS 15 > or = 7 indicates the presence of clinically significant depression. Men were also grouped according to the severity of symptoms: "no symptoms" (GDS-15 = 0), "questionable" (1 < or = GDS-15 < or = 4), "mild to moderate" (5 < or = GDS-15 < or = 9), and "severe" (GDS-15 > or = 10). Participants listed all medications used regularly. We used the Western Australian Data Linkage System to monitor mortality. RESULTS: There were 883 deaths between the study assessment and the 30th June 2008 (mean follow-up of participants: 6.0+/-1.1 years). The adjusted mortality hazard (MH) of men with clinically significant depression was 1.98 (95%CI = 1.61-2.43), and increased with the severity of symptoms: 1.39 (95%CI = 1.13-1.71) for questionable, 2.71 (95%CI = 2.13-3.46) for mild/moderate, and 3.32 (95%CI: 2.31-4.78) for severe depression. The use of antidepressants increased MH (HR = 1.31, 95%CI = 1.02-1.68). Compared with men who were not depressed and were not taking antidepressants, MH increased from 1.22 (95%CI = 0.91-1.63) for men with no depression who were using antidepressants to 1.85 (95%CI = 1.47-2.32) for participants who were depressed but were not using antidepressants, and 2.97 (95%CI = 1.94-4.54) for those who were depressed and were using antidepressants. All analyses were adjusted for age, educational attainment, migrant status, physical activity, smoking and alcohol use and the Charlson comorbidity index. CONCLUSIONS: The mortality associated with depression increases with the severity of depressive symptoms and is largely independent of comorbid conditions. The use of antidepressants does not reduce the mortality rates of older men with persistent symptoms of depression. PMID- 20585645 TI - Classification of dengue fever patients based on gene expression data using support vector machines. AB - BACKGROUND: Symptomatic infection by dengue virus (DENV) can range from dengue fever (DF) to dengue haemorrhagic fever (DHF), however, the determinants of DF or DHF progression are not completely understood. It is hypothesised that host innate immune response factors are involved in modulating the disease outcome and the expression levels of genes involved in this response could be used as early prognostic markers for disease severity. METHODOLOGY/PRINCIPAL FINDINGS: mRNA expression levels of genes involved in DENV innate immune responses were measured using quantitative real time PCR (qPCR). Here, we present a novel application of the support vector machines (SVM) algorithm to analyze the expression pattern of 12 genes in peripheral blood mononuclear cells (PBMCs) of 28 dengue patients (13 DHF and 15 DF) during acute viral infection. The SVM model was trained using gene expression data of these genes and achieved the highest accuracy of approximately 85% with leave-one-out cross-validation. Through selective removal of gene expression data from the SVM model, we have identified seven genes (MYD88, TLR7, TLR3, MDA5, IRF3, IFN-alpha and CLEC5A) that may be central in differentiating DF patients from DHF, with MYD88 and TLR7 observed to be the most important. Though the individual removal of expression data of five other genes had no impact on the overall accuracy, a significant combined role was observed when the SVM model of the two main genes (MYD88 and TLR7) was re-trained to include the five genes, increasing the overall accuracy to approximately 96%. CONCLUSIONS/SIGNIFICANCE: Here, we present a novel use of the SVM algorithm to classify DF and DHF patients, as well as to elucidate the significance of the various genes involved. It was observed that seven genes are critical in classifying DF and DHF patients: TLR3, MDA5, IRF3, IFN-alpha, CLEC5A, and the two most important MYD88 and TLR7. While these preliminary results are promising, further experimental investigation is necessary to validate their specific roles in dengue disease. PMID- 20585646 TI - Economic status, education and empowerment: implications for maternal health service utilization in developing countries. AB - BACKGROUND: Relative to the attention given to improving the quality of and access to maternal health services, the influence of women's socio-economic situation on maternal health care use has received scant attention. The objective of this paper is to examine the relationship between women's economic, educational and empowerment status, introduced as the 3Es, and maternal health service utilization in developing countries. METHODS/PRINCIPAL FINDINGS: The analysis uses data from the most recent Demographic and Health Surveys conducted in 31 countries for which data on all the 3Es are available. Separate logistic regression models are fitted for modern contraceptive use, antenatal care and skilled birth attendance in relation to the three covariates of interest: economic, education and empowerment status, additionally controlling for women's age and residence. We use meta-analysis techniques to combine and summarize results from multiple countries. The 3Es are significantly associated with utilization of maternal health services. The odds of having a skilled attendant at delivery for women in the poorest wealth quintile are 94% lower than that for women in the highest wealth quintile and almost 5 times higher for women with complete primary education relative to those less educated. The likelihood of using modern contraception and attending four or more antenatal care visits are 2.01 and 2.89 times, respectively, higher for women with complete primary education than for those less educated. Women with the highest empowerment score are between 1.31 and 1.82 times more likely than those with a null empowerment score to use modern contraception, attend four or more antenatal care visits and have a skilled attendant at birth. CONCLUSIONS/SIGNIFICANCE: Efforts to expand maternal health service utilization can be accelerated by parallel investments in programs aimed at poverty eradication (MDG 1), universal primary education (MDG 2), and women's empowerment (MDG 3). PMID- 20585647 TI - Involvement of AMPK in alcohol dehydrogenase accentuated myocardial dysfunction following acute ethanol challenge in mice. AB - OBJECTIVES: Binge alcohol drinking often triggers myocardial contractile dysfunction although the underlying mechanism is not fully clear. This study was designed to examine the impact of cardiac-specific overexpression of alcohol dehydrogenase (ADH) on ethanol-induced change in cardiac contractile function, intracellular Ca(2+) homeostasis, insulin and AMP-dependent kinase (AMPK) signaling. METHODS: ADH transgenic and wild-type FVB mice were acutely challenged with ethanol (3 g/kg/d, i.p.) for 3 days. Oral glucose tolerance test, cardiac AMP/ATP levels, cardiac contractile function, intracellular Ca(2+) handling and AMPK signaling (including ACC and LKB1) were examined. RESULTS: Ethanol exposure led to glucose intolerance, elevated plasma insulin, compromised cardiac contractile and intracellular Ca(2+) properties, downregulated protein phosphatase PP2A subunit and PPAR-gamma, as well as phosphorylation of AMPK, ACC and LKB1, all of which except plasma insulin were overtly accentuated by ADH transgene. Interestingly, myocardium from ethanol-treated FVB mice displayed enhanced expression of PP2Calpha and PGC-1alpha, decreased insulin receptor expression as well as unchanged expression of Glut4, the response of which was unaffected by ADH. Cardiac AMP-to-ATP ratio was significantly enhanced by ethanol exposure with a more pronounced increase in ADH mice. In addition, the AMPK inhibitor compound C (10 microM) abrogated acute ethanol exposure-elicited cardiomyocyte mechanical dysfunction. CONCLUSIONS: In summary, these data suggest that the ADH transgene exacerbated acute ethanol toxicity-induced myocardial contractile dysfunction, intracellular Ca(2+) mishandling and glucose intolerance, indicating a role of ADH in acute ethanol toxicity-induced cardiac dysfunction possibly related to altered cellular fuel AMPK signaling cascade. PMID- 20585648 TI - Evolutionary dead end in the Galapagos: divergence of sexual signals in the rarest of Darwin's finches. AB - Understanding the mechanisms underlying speciation remains a challenge in evolutionary biology. The adaptive radiation of Darwin's finches is a prime example of species formation, and their study has revealed many important insights into evolutionary processes. Here, we report striking differences in mating signals (songs), morphology and genetics between the two remnant populations of Darwin's mangrove finch Camarhynchus heliobates, one of the rarest species in the world. We also show that territorial males exhibited strong discrimination of sexual signals by locality: in response to foreign songs, males responded weaker than to songs from their own population. Female responses were infrequent and weak but gave approximately similar results. Our findings not only suggest speciation in the mangrove finch, thereby providing strong support for the central role of sexual signals during speciation, but they have also implications for the conservation of this iconic bird. If speciation is complete, the eastern species will face imminent extinction, because it has a population size of only 5-10 individuals. PMID- 20585649 TI - Human uterine wall tension trajectories and the onset of parturition. AB - Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension. PMID- 20585650 TI - R-Ras regulates migration through an interaction with filamin A in melanoma cells. AB - BACKGROUND: Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins. METHODS AND FINDINGS: We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin beta1, beta2 and beta7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaDelta3) abrogated this interaction. In M2 melanoma cells active R-Ras co localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaDelta3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly. CONCLUSIONS: These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration. PMID- 20585651 TI - Social networks shape the transmission dynamics of hepatitis C virus. AB - Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in Sao Paulo state, Brazil. We show that different viral genotypes entered Sao Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in Sao Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies. PMID- 20585653 TI - Open access to the scientific journal literature: situation 2009. AB - BACKGROUND: The Internet has recently made possible the free global availability of scientific journal articles. Open Access (OA) can occur either via OA scientific journals, or via authors posting manuscripts of articles published in subscription journals in open web repositories. So far there have been few systematic studies showing how big the extent of OA is, in particular studies covering all fields of science. METHODOLOGY/PRINCIPAL FINDINGS: The proportion of peer reviewed scholarly journal articles, which are available openly in full text on the web, was studied using a random sample of 1837 titles and a web search engine. Of articles published in 2008, 8.5% were freely available at the publishers' sites. For an additional 11.9% free manuscript versions could be found using search engines, making the overall OA percentage 20.4%. Chemistry (13%) had the lowest overall share of OA, Earth Sciences (33%) the highest. In medicine, biochemistry and chemistry publishing in OA journals was more common. In all other fields author-posted manuscript copies dominated the picture. CONCLUSIONS/SIGNIFICANCE: The results show that OA already has a significant positive impact on the availability of the scientific journal literature and that there are big differences between scientific disciplines in the uptake. Due to the lack of awareness of OA-publishing among scientists in most fields outside physics, the results should be of general interest to all scholars. The results should also interest academic publishers, who need to take into account OA in their business strategies and copyright policies, as well as research funders, who like the NIH are starting to require OA availability of results from research projects they fund. The method and search tools developed also offer a good basis for more in-depth studies as well as longitudinal studies. PMID- 20585652 TI - A conserved role for syndecan family members in the regulation of whole-body energy metabolism. AB - Syndecans are a family of type-I transmembrane proteins that are involved in cell matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage. Next, we examined the effects of a viable dSdc mutant on Drosophila whole-body energy metabolism and associated traits. We observed that young flies homozygous for the dSdc mutation had reduced fat storage and slept longer than homozygous wild-type flies. They also displayed significantly reduced metabolic rate, lower expression of spargel (the Drosophila homologue of PGC-1), and reduced mitochondrial respiration. Compared to control flies, dSdc mutants had lower expression of brain insulin-like peptides, were less fecund, more sensitive to starvation, and had reduced life span. Finally, we tested for association between single nucleotide polymorphisms (SNPs) in the human SDC4 gene and variation in body composition, metabolism, glucose homeostasis, and sleep traits in a cohort of healthy early pubertal children. We found that SNP rs4599 was significantly associated with resting energy expenditure (P = 0.001 after Bonferroni correction) and nominally associated with fasting glucose levels (P = 0.01) and sleep duration (P = 0.044). On average, children homozygous for the minor allele had lower levels of glucose, higher resting energy expenditure, and slept shorter than children homozygous for the common allele. We also observed that SNP rs1981429 was nominally associated with lean tissue mass (P = 0.035) and intra-abdominal fat (P = 0.049), and SNP rs2267871 with insulin sensitivity (P = 0.037). Collectively, our results in Drosophila and humans argue that syndecan family members play a key role in the regulation of body metabolism. PMID- 20585654 TI - Characterization of coastal urban watershed bacterial communities leads to alternative community-based indicators. AB - BACKGROUND: Microbial communities in aquatic environments are spatially and temporally dynamic due to environmental fluctuations and varied external input sources. A large percentage of the urban watersheds in the United States are affected by fecal pollution, including human pathogens, thus warranting comprehensive monitoring. METHODOLOGY/PRINCIPAL FINDINGS: Using a high-density microarray (PhyloChip), we examined water column bacterial community DNA extracted from two connecting urban watersheds, elucidating variable and stable bacterial subpopulations over a 3-day period and community composition profiles that were distinct to fecal and non-fecal sources. Two approaches were used for indication of fecal influence. The first approach utilized similarity of 503 operational taxonomic units (OTUs) common to all fecal samples analyzed in this study with the watershed samples as an index of fecal pollution. A majority of the 503 OTUs were found in the phyla Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. The second approach incorporated relative richness of 4 bacterial classes (Bacilli, Bacteroidetes, Clostridia and alpha-proteobacteria) found to have the highest variance in fecal and non-fecal samples. The ratio of these 4 classes (BBC:A) from the watershed samples demonstrated a trend where bacterial communities from gut and sewage sources had higher ratios than from sources not impacted by fecal material. This trend was also observed in the 124 bacterial communities from previously published and unpublished sequencing or PhyloChip- analyzed studies. CONCLUSIONS/SIGNIFICANCE: This study provided a detailed characterization of bacterial community variability during dry weather across a 3-day period in two urban watersheds. The comparative analysis of watershed community composition resulted in alternative community-based indicators that could be useful for assessing ecosystem health. PMID- 20585655 TI - Towards the rational design of a candidate vaccine against pregnancy associated malaria: conserved sequences of the DBL6epsilon domain of VAR2CSA. AB - BACKGROUND: Placental malaria is a disease linked to the sequestration of Plasmodium falciparum infected red blood cells (IRBC) in the placenta, leading to reduced materno-fetal exchanges and to local inflammation. One of the virulence factors of P. falciparum involved in cytoadherence to chondroitin sulfate A, its placental receptor, is the adhesive protein VAR2CSA. Its localisation on the surface of IRBC makes it accessible to the immune system. VAR2CSA contains six DBL domains. The DBL6epsilon domain is the most variable. High variability constitutes a means for the parasite to evade the host immune response. The DBL6epsilon domain could constitute a very attractive basis for a vaccine candidate but its reported variability necessitates, for antigenic characterisations, identifying and classifying commonalities across isolates. METHODOLOGY/PRINCIPAL FINDINGS: Local alignment analysis of the DBL6epsilon domain had revealed that it is not as variable as previously described. Variability is concentrated in seven regions present on the surface of the DBL6epsilon domain. The main goal of our work is to classify and group variable sequences that will simplify further research to determine dominant epitopes. Firstly, variable sequences were grouped following their average percent pairwise identity (APPI). Groups comprising many variable sequences sharing low variability were found. Secondly, ELISA experiments following the IgG recognition of a recombinant DBL6epsilon domain, and of peptides mimicking its seven variable blocks, allowed to determine an APPI cut-off and to isolate groups represented by a single consensus sequence. CONCLUSIONS/SIGNIFICANCE: A new sequence approach is used to compare variable regions in sequences that have extensive segmental gene relationship. Using this approach, the VAR2CSA DBL6 domain is composed of 7 variable blocks with limited polymorphism. Each variable block is composed of a limited number of consensus types. Based on peptide based ELISA, variable blocks with 85% or greater sequence identity are expected to be recognized equally well by antibody and can be considered the same consensus type. Therefore, the analysis of the antibody response against the classified small number of sequences should be helpful to determine epitopes. PMID- 20585656 TI - Characterization of S3Pvac anti-cysticercosis vaccine components: implications for the development of an anti-cestodiasis vaccine. AB - BACKGROUND: Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms. CONCLUSIONS/SIGNIFICANCE: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates. PMID- 20585657 TI - Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice. AB - Transforming growth factor-beta-activated kinase 1 (TAK1) is a member of the NF kappaB pathway and regulates inflammatory responses. We previously showed that TAK1 also regulates keratinocyte growth, differentiation, and apoptosis. However, it is unknown whether TAK1 has any role in epithelial-mesenchymal interactions. To examine this possibility, we studied the role of TAK1 in mouse hair follicle development and cycling as an instructive model system. By comparing keratinocyte specific TAK1-deficient mice (Map3k7(fl/fl)K5-Cre) with control mice, we found that the number of hair germs (hair follicles precursors) in Map3k7(fl/fl)K5-Cre mice was significantly reduced at E15.5, and that subsequent hair follicle morphogenesis was retarded. Next, we analyzed the role of TAK1 in the cyclic remodeling in follicles by analyzing hair cycle progression in mice with a tamoxifen-inducible keratinocyte-specific TAK1 deficiency (Map3k7(fl/fl)K14-Cre ER(T2)). After active hair growth (anagen) was induced by depilation, TAK1 was deleted by topical tamoxifen application. This resulted in significantly retarded anagen development in TAK1-deficient mice. Deletion of TAK1 in hair follicles that were already in anagen induced premature, apoptosis-driven hair follicle regression, along with hair follicle damage. These studies provide the first evidence that the inflammatory mediator TAK1 regulates hair follicle induction and morphogenesis, and is required for anagen induction and anagen maintenance. PMID- 20585658 TI - The relBE2Spn toxin-antitoxin system of Streptococcus pneumoniae: role in antibiotic tolerance and functional conservation in clinical isolates. AB - Type II (proteic) chromosomal toxin-antitoxin systems (TAS) are widespread in Bacteria and Archaea but their precise function is known only for a limited number of them. Out of the many TAS described, the relBE family is one of the most abundant, being present in the three first sequenced strains of Streptococcus pneumoniae (D39, TIGR4 and R6). To address the function of the pneumococcal relBE2Spn TAS in the bacterial physiology, we have compared the response of the R6-relBE2Spn wild type strain with that of an isogenic derivative, Delta relB2Spn under different stress conditions such as carbon and amino acid starvation and antibiotic exposure. Differences on viability between the wild type and mutant strains were found only when treatment directly impaired protein synthesis. As a criterion for the permanence of this locus in a variety of clinical strains, we checked whether the relBE2Spn locus was conserved in around 100 pneumococcal strains, including clinical isolates and strains with known genomes. All strains, although having various types of polymorphisms at the vicinity of the TA region, contained a functional relBE2Spn locus and the type of its structure correlated with the multilocus sequence type. Functionality of this TAS was maintained even in cases where severe rearrangements around the relBE2Spn region were found. We conclude that even though the relBE2Spn TAS is not essential for pneumococcus, it may provide additional advantages to the bacteria for colonization and/or infection. PMID- 20585659 TI - Mild sensory stimulation completely protects the adult rodent cortex from ischemic stroke. AB - Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential. PMID- 20585660 TI - Mu-opioid receptors transiently activate the Akt-nNOS pathway to produce sustained potentiation of PKC-mediated NMDAR-CaMKII signaling. AB - BACKGROUND: In periaqueductal grey (PAG) matter, cross-talk between the Mu-opioid receptor (MOR) and the glutamate N-methyl-D-Aspartate receptor (NMDAR)-CaMKII pathway supports the development of analgesic tolerance to morphine. In neurons, histidine triad nucleotide binding protein 1 (HINT1) connects the regulators of G protein signaling RGSZ1 and RGSZ2 to the C terminus of the MOR. In response to morphine, this HINT1-RGSZ complex binds PKCgamma, and afterwards, the interplay between PKCgamma, Src and Gz/Gi proteins leads to sustained potentiation of NMDAR mediated glutamate responses. METHODOLOGY/PRINCIPAL FINDINGS: Following an intracerebroventricular (icv) injection of 10 nmol morphine, Akt was recruited to the synaptosomal membrane and activated by Thr308 and Ser473 phosphorylation. The Akt activation was immediately transferred to neural Nitric Oxide Synthase (nNOS) Ser1417. Afterwards, nitric oxide (NO)-released zinc ions recruited PKCgamma to the MOR to promote the Src-mediated phosphorylation of the Tyr1325 NMDAR2A subunit. This action increased NMDAR calcium flux and CaMKII was activated in a calcium-calmodulin dependent manner. CaMKII then acted on nNOS Ser847 to produce a sustained reduction in NO levels. The activation of the Akt-nNOS pathway was also reduced by the binding of these proteins to the MOR-HINT1 complex where they remained inactive. Tolerance to acute morphine developed as a result of phosphorylation of MOR cytosolic residues, uncoupling from the regulated G proteins which are transferred to RGSZ2 proteins. The diminished effect of morphine was prevented by LNNA, an inhibitor of nNOS function, and naltrindole, a delta-opioid receptor antagonist that also inhibits Akt. CONCLUSIONS/SIGNIFICANCE: Analysis of the regulatory phosphorylation of the proteins included in the study indicated that morphine produces a transient activation of the Akt/PKB-nNOS pathway. This activation occurs upstream of PKCgamma and Src mediated potentiation of NMDAR activity, ultimately leading to morphine tolerance. In summary, the Akt-nNOS pathway acts as a primer for morphine-triggered events which leads to the sustained potentiation of the NMDAR CaMKII pathway and MOR inhibition. PMID- 20585661 TI - A nested case-control study of intrauterine exposure to persistent organochlorine pollutants in relation to risk of type 1 diabetes. AB - BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case control study within a biobank in Malmo, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1 dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes. PMID- 20585662 TI - Connective tissue growth factor in regulation of RhoA mediated cytoskeletal tension associated osteogenesis of mouse adipose-derived stromal cells. AB - BACKGROUND: Cytoskeletal tension is an intracellular mechanism through which cells convert a mechanical signal into a biochemical response, including production of cytokines and activation of various signaling pathways. METHODS/PRINCIPAL FINDINGS: Adipose-derived stromal cells (ASCs) were allowed to spread into large cells by seeding them at a low-density (1,250 cells/cm(2)), which was observed to induce osteogenesis. Conversely, ASCs seeded at a high density (25,000 cells/cm(2)) featured small cells that promoted adipogenesis. RhoA and actin filaments were altered by changes in cell size. Blocking actin polymerization by Cytochalasin D influenced cytoskeletal tension and differentiation of ASCs. To understand the potential regulatory mechanisms leading to actin cytoskeletal tension, cDNA microarray was performed on large and small ASCs. Connective tissue growth factor (CTGF) was identified as a major regulator of osteogenesis associated with RhoA mediated cytoskeletal tension. Subsequently, knock-down of CTGF by siRNA in ASCs inhibited this osteogenesis. CONCLUSIONS/SIGNIFICANCE: We conclude that CTGF is important in the regulation of cytoskeletal tension mediated ASC osteogenic differentiation. PMID- 20585663 TI - Ascorbate peroxidase from Leishmania major controls the virulence of infective stage of promastigotes by regulating oxidative stress. AB - BACKGROUND: Peroxidase represents a heterogeneous group of distinct enzyme family that plays extremely diverse biological functions. Ascorbate peroxidase from Leishmania major (LmAPX) has been shown to be central to the redox defense system of Leishmania. To investigate further its exact physiological role in Leishmania, we attempted to create LmAPX -knockout mutants by gene replacement in L. major strains. METHODOLOGY/PRINCIPAL FINDINGS: The null mutant cell culture contains a higher percentage of metacyclic and apoptotic cells compared to both wild type and LmAPX overexpressing cells. Flowcytometric analysis reveals the presence of a higher concentration of intracellular H(2)O(2), indicative of increased oxidative stress in parasites lacking LmAPX. IC(50) value for exogenously added H(2)O(2) shows that deletion of LmAPX in L. major renders the cell more susceptible to H(2)O(2). Real time PCR studies demonstrate an elevated mRNA level of non selenium glutathione peroxidase in LmAPX null mutant cell line, suggesting that these enzymes were induced to compensate the LmAPX enzyme. The null mutant cells exhibit hypervirulence after infection with macrophages as well as inoculation into BALB/c mice; in contrast, overexpressing cells show avirulence. CONCLUSIONS/SIGNIFICANCE: Collectively, these data provide strong evidence that LmAPX is an important factor for controlling parasite differentiation and survival within macrophages. PMID- 20585664 TI - Multisensory perceptual learning of temporal order: audiovisual learning transfers to vision but not audition. AB - BACKGROUND: An outstanding question in sensory neuroscience is whether the perceived timing of events is mediated by a central supra-modal timing mechanism, or multiple modality-specific systems. We use a perceptual learning paradigm to address this question. METHODOLOGY/PRINCIPAL FINDINGS: Three groups were trained daily for 10 sessions on an auditory, a visual or a combined audiovisual temporal order judgment (TOJ). Groups were pre-tested on a range TOJ tasks within and between their group modality prior to learning so that transfer of any learning from the trained task could be measured by post-testing other tasks. Robust TOJ learning (reduced temporal order discrimination thresholds) occurred for all groups, although auditory learning (dichotic 500/2000 Hz tones) was slightly weaker than visual learning (lateralised grating patches). Crossmodal TOJs also displayed robust learning. Post-testing revealed that improvements in temporal resolution acquired during visual learning transferred within modality to other retinotopic locations and orientations, but not to auditory or crossmodal tasks. Auditory learning did not transfer to visual or crossmodal tasks, and neither did it transfer within audition to another frequency pair. In an interesting asymmetry, crossmodal learning transferred to all visual tasks but not to auditory tasks. Finally, in all conditions, learning to make TOJs for stimulus onsets did not transfer at all to discriminating temporal offsets. These data present a complex picture of timing processes. CONCLUSIONS/SIGNIFICANCE: The lack of transfer between unimodal groups indicates no central supramodal timing process for this task; however, the audiovisual-to-visual transfer cannot be explained without some form of sensory interaction. We propose that auditory learning occurred in frequency-tuned processes in the periphery, precluding interactions with more central visual and audiovisual timing processes. Functionally the patterns of featural transfer suggest that perceptual learning of temporal order may be optimised to object-centered rather than viewer-centered constraints. PMID- 20585665 TI - Detection of DNA and indirect detection of tumor cells based on circular strand replacement DNA polymerization on electrode. AB - The chronocoulometric detection of DNA was carried out based on circular strand replacement DNA polymerization on a screen-printed electrode, and extended to quantify tumor cells with the aid of aptamer recognition. PMID- 20585666 TI - Recent advances in stereoselective glycosylation through intramolecular aglycon delivery. AB - Methodology toward the stereoselective 1,2-cis glycoside linkage using intramolecular aglycon delivery (IAD) has been extensively developed. In the last two decades, progress has been made using various mixed acetal linkages and a number of glycosyl donor moieties to develop novel IAD strategies, mainly based on formation of acetal linkages. This account summarizes the newest naphthylmethyl (NAP) ether-mediated IAD as well as all the types of mediations for stereospecific construction of various 1,2-cis linkages, not only for beta mannopyranoside, but also for other linkages almost without exception, including beta-L-rhamnoside. PMID- 20585667 TI - Phosphido-bridged Ta/Rh bimetallic complex: synthesis, structure, and catalytic hydrosilylation of acetophenone. AB - Reaction of Cp2TaH3 (1) with ClPEt2 gives the insertion product [Cp2TaH2(PHEt2)]Cl (5), which upon deprotonation with LiN(SiMe3)2 affords the phosphido complex Cp2TaH2(PEt2) (6) as the kinetic product. The latter transforms by a first-order reaction during the course of 3.5 days to the phosphine complex Cp2TaH(PHEt2) (7). Repetition of this insertion/deprotonation sequence gives the compounds [Cp2Ta(PHEt2)2]Cl (8) and Cp2Ta(PEt2)(PHEt2) (9). Reaction of the latter with 0.5[(MU-Cl)Rh(eta2-C2H4)]2 in the presence of LiN(SiMe3)2 gives the bimetallic complex Cp2Ta(MU-PEt2)2Rh(eta2-C2H4) (10), which was studied by NMR and X-ray diffraction analysis. Complex 10 catalyses the hydrosilylation of acetophenone by PhMeSiH2. PMID- 20585673 TI - The use of phosphonates for constructing 3d-4f clusters at high oxidation states: synthesis and characterization of two unusual heterometallic CeMn complexes. AB - The use of phosphonic acids in the synthesis of mixed-metal CeMn complexes has led to the formation of two phosphonate complexes with unusual topologies: [Ce(2)Mn(6)O(6)(OH)(5)(t-BuPO(3))(6)(O(2)CMe)(3)] x 53 H(2)O (1 x 53 H(2)O) and [Ce(22)Mn(12)O(34)(MePO(3))(12)(O(2)CMe)(33)(OMe)(6)(NO(3))(H(2)O)(12)](n) (2). The two mixed-metal CeMn complexes were both prepared from a reaction system containing Mn(O(2)CMe)(2) and (NH(4))(2)[Ce(NO(3))(6)] with similar procedures except for using different phosphonic acids (tert-butylphosphonic acid and methylphosphonic acid, respectively) as coligands. Both complexes possess rare topology of triangular type, with compound 1 being a 0D discrete cluster, whereas, compound 2 is a 1D polymer. The octanuclear core of complex 1 is composed of three symmetry equivalent distorted cubanes {Ce(IV)(2)Mn(IV)(2)O(2)(OH)(2)} sharing a trigonal-bipyramidal unit {Ce(IV)(2)(OH)(3)} in the centre. Compound 2 is a one-dimensional chain polymer of identical Ce(22)Mn(12)O(34) units linked together by NO(3)(-) and MeCO(2)(-) groups, while the Ce(22)Mn(12)O(34) unit is constituted by two centrosymmetric Ce(9)(IV)Ce(2)(III)Mn(IV)(6)O(17) subunits, which features three identical distorted cubanes {Ce(IV)(2)Mn(IV)(2)O(4)} connecting to a central trigonal bipyramidal unit {Ce(IV)(3)O(2)}, and two additional Ce(III) ions capping the top and bottom of the central trigonal bipyramid by six MePO(3)(2-) ligands. Complexes 1 and 2 are the first high-nuclearity Mn/Ln aggregates reported to date using phosphonates as ligands. Magnetic susceptibility measurements reveal that compound 1 displays dominant ferromagnetic interactions between the adjacent metal ions with the best fit parameters for the exchanges are J(1) = 6.186 cm( 1), J(2) = 4.172 cm(-1), and with a result of S = 9 ground state confirmed by the M versus HT(-1) data, which indicates the spins of all the six Mn(IV) ions in the cluster are parallel to each other. In contrast, the data for 2 reveals overall antiferromagnetic couplings within the cluster and a resulting S = 6 ground state. Both the in-phase signal chi'(M)T and out-of-phase signal chi''(M) of the two complexes exhibit frequency-dependent below approximate 3 K. PMID- 20585674 TI - Nonlinear Hammett plots in pyridinolysis of 2,4-dinitrophenyl X-substituted benzoates: change in RDS versus resonance contribution. AB - Second-order rate constants (k(OH)-) have been measured for nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzoates (1a-j) with Z substituted pyridines in 80 mol% H(2)O/20 mol% DMSO at 25.0 +/- 0.1 degrees C. The Hammett plots for the reactions of 1a-j with pyridines consist of two intersecting straight lines, i.e., a large rho value for the reactions of substrates (1a-c) possessing an electron-donating group (EDG) in the benzoyl moiety and a small one for substrates (1e-j) bearing an electron-withdrawing group (EWG). The nonlinear Hammett plots have been attributed to stabilization of the ground state of substrates 1a-c through resonance interactions between the electron-donating substituent and the carbonyl functionality, since the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with large r values. It has been shown that substrates are not unusually more reactive than would be expected from the Hammett substituent constants, but rather, substrates 1a-c exhibit lower reactivity than would be predicted. The Bronsted-type plots for pyridinolysis of 1a-j are linear with beta(nuc) = 0.74-0.98, indicating that the reaction proceeds through a stepwise mechanism in which the second step is the RDS. It has been concluded that the electronic nature of the substituent X in the benzoyl moiety does not influence the RDS, but the degree of bond formation (or the effective charge on the nucleophilic site) in the transition state becomes more significant as the substituent X changes from a strong EDG to a strong EWG. PMID- 20585675 TI - Neodymium(III) phosphinidene complexes supported by pentamethylcyclopentadienyl and hydrotris(pyrazolyl)borate ligands. AB - Synthesis of new neodymium(III) phosphinidene complexes from a neodymium(III) phosphinidene iodide [(mu-PC(6)H(3)-2,6-(i)Pr(2))Nd(I)(THF)(3)](2) (1) was studied. The metathesis reaction of 1 with KC(5)Me(5) (KCp*) gave a neodymium(III) pentamethylcyclopentadienyl phosphinidene complex [(mu-PC(6)H(3) 2,6-(i)Pr(2))(C(5)Me(5))Nd(THF)](2) (2), and that with potassium hydrotris(pyrazolyl)borate KHB(3-phenylpz)(3) (KTp(Ph)) generated a neodymium(III) hydrotris(pyrazolyl)borate phosphinidene complex [(mu-PC(6)H(3) 2,6-(i)Pr(2))(Tp(Ph*))Nd(THF)](2) (3) and a C-H bond activation byproduct [kappa(4)(N,N',N'',C(Ph))-Tp(Ph)]Tp(Ph)Nd (4). Complexes 2-4 have been characterized by single-crystal X-ray diffraction analysis. PMID- 20585676 TI - Electrical modeling of the influence of medium conductivity on electroporation. AB - Electroporation is the phenomenon in which cell membrane permeability is increased by exposing the cell to short high electric field pulses. Experimental data show that the amount of permeabilization depends on the conductivity of the extracellular medium. If medium conductivity decreases then it is necessary to deliver a pulse of larger field amplitude in order to achieve the same effect. Models that do not take into account the permeabilization effect on the membrane conductivity cannot reproduce qualitatively the experimental observations. Here we employ an exponential function for describing the strong dependence of membrane conductivity on transmembrane potential. Combining that model with numerical methods we demonstrate that the dependence on medium conductivity can be explained as being the result of increased membrane conductance due to electroporation. As experimentally observed, extracellular conductivities of about 1 and 0.1 S m(-1) yield very similar results, however, for lower conductivities (<0.01 S m(-1)) the model predicts that significantly higher field magnitudes will be required to achieve the same amount of permeabilization. PMID- 20585677 TI - Infra-red and Raman spectroscopy of free-base and zinc phthalocyanines isolated in matrices. AB - The infrared absorption spectra of matrix-isolated zinc phthalocyanine (ZnPc) and free-base phthalocyanine (H(2)Pc) have been recorded in the region from 400 to 4000 cm(-1) in solid N(2), Ar, Kr and Xe. Raman spectra have been recorded in doped KBr pellets. The isotopomers HDPc and D(2)Pc have been synthesised in an attempt to resolve the conflicting assignments that currently exist in the literature for the N-H bending modes in H(2)Pc spectra. A complete correlation between the vibrational modes of the three free-base isotopomers and ZnPc has been achieved. Comparison of the IR and Raman spectroscopic results, obtained with isotopic substitution and with predictions from large basis set ab initio calculations, allows identification of the in-plane (IP) and out-of-plane (OP) N H bending modes. The largest IP isotope shift is observed in the IR at 1046 cm( 1) and at 1026 cm(-1) in Raman spectra while the largest effect in the OP bending modes is at 764 cm(-1). OP bending modes are too weak to be observed in the experimental Raman data. The antisymmetric N-H stretching mode is observed at approximately 3310 cm(-1) in low temperature solids slightly blue shifted from, but entirely consistent with the literature KBr data. With the exception of the N H stretches, the recorded H/D isotope shifts in all the N-H vibrations are complex, with the IP bending modes exhibiting small nu(H)/nu(D) ratios (the largest value is 1.089) while one of the observed OP modes has a ratio < 1. DFT results reveal that the small ratios arise in particular from strong coupling of the N-H IP bending modes with IP stretching modes of C-N bonds. The unexpected finding of a nu(H)/nu(D) ratio smaller than one was analysed theoretically by examining the evolution of the frequencies of the free base by increasing the mass from H to D in a continuous manner. A consequence of this frequency increase in the heavier isotopomer is that the direction of the N-D OP bend is reversed from the N-H OP bend. PMID- 20585678 TI - New horizons in organo-f-block chemistry. PMID- 20585679 TI - Enhanced electrogenerated chemiluminescence of a ruthenium tris(2,2')bipyridyl/tripropylamine system on a boron-doped diamond nanograss array. AB - Significant enhancement of the ECL signals from the Ru(bpy)(3)(2+)/TPA system was achieved when using a BDD nanograss array, mainly because of the highly facile oxidation of TPA. The facile oxidation of TPA is due to the superior properties of the BDD nanograss array, such as improved electrocatalytic activity and accelerated electron transfer. PMID- 20585680 TI - Polymeric self-assembled monolayers derived from surface-active copolymers: a modular approach to functionalized surfaces. AB - Physical or covalent adsorption of surface-active block or random copolymers consisting of anchoring units and functional units onto solid surfaces yields polymeric self-assembled monolayers (PSAMs) with designed chemical and morphological structures and functionalities. This tutorial review provides an overview of PSAMs derived from various types of copolymers. It also discusses design principles for PSAMs to tune interfacial and surface interactions of materials for potential applications. PMID- 20585681 TI - Carbohydrate functionalized carbon nanotubes and their applications. AB - Carbon nanotubes (CNTs) have attracted tremendous attention in biomedical applications due to their molecular size and unique properties. This tutorial review summarizes the strategies to functionalize CNTs with bioactive carbohydrates, which improve their solubility, biocompatibility and biofunctionalities while preserving their desired properties. In addition, studies on the usage of carbohydrate functionalized CNTs to detect bacteria, to bind to specific lectins, to deliver glycomimetic drug molecules into cells and to probe cellular activities as biosensors are reviewed. Improvement in biocompatibility and introduction of bio-functionalities by integration of carbohydrate with CNTs are paving the way to glyconanotechnology and may provide new tools for glycobiological studies. PMID- 20585682 TI - A density-functional theory study of electrochemical adsorption of sulfuric acid anions on Pt(111). AB - A density-functional theory study of the electrochemical adsorption of sulfuric acid anions was conducted at the Pt(111)/electrolyte interface over a wide range of electrode potential, including the anomalous region of the hydrogen voltammogram of this electrode. We focus on the precise nature of the binding species and their bonding to the surface, identifying the adsorbed species as a function of electrode potential. In particular, the origin of anomalous or so called "butterfly" feature in this voltammogram between +0.30 and +0.50 V vs. the reference hydrogen electrode and the nature of the adsorbed species on the Pt(111) surface in this potential range were explicated. PMID- 20585683 TI - Reverse Monte Carlo modeling of ion conducting network glasses: an evaluation based on molecular dynamics simulations. AB - We investigate the quality of structural models generated by the Reverse Monte Carlo (RMC) method in a typical application to glass systems. To this end we calculate diffraction data from a Li(2)O-SiO(2) molecular dynamics (MD) simulation and use it, in addition to minimal pair distances and coordination numbers of silicon (oxygen) to oxygen (silicon) ions, as input for RMC modeling. Then we compare partial radial distribution functions, coordination numbers, bond angles, and ring sizes predicted by the RMC models with those of the MD system. It is found that partial distribution functions and properties on small lengths scales, as distributions of coordination numbers and bond angles, are well reproduced by the RMC modeling. Properties in the medium-range order regime are, however, not well captured, as is demonstrated by comparison of ring size distributions. Due care therefore has to be exercised when extracting structural features from RMC models in this medium-range order regime. In particular we show that the occurrence of such features can be a mere consequence of the chosen starting configuration. PMID- 20585684 TI - Integral and differential cross sections of reactions relevant to astrochemistry. AB - In recent years, kinetic experiments have shown that, contrary to the Arrhenius concept, many neutral-neutral reactions remain fast at very low temperature. Such behaviour ranks them as important processes to be considered in the chemical networks that model the synthesis and the fate of molecules observed in the interstellar medium. This Perspective Article aims to review complementary crossed beam experiments of relevant neutral-neutral reactions performed in the low collision energy regime. A few selected reactions are considered, with particular emphasis on carbon-atom reactions with unsaturated hydrocarbons. It is shown, with the example of the C + C(2)H(2) system, that the conjunction of kinetic and dynamic experiments can provide a consistent set of detailed rate coefficients for a multichannel reaction, relevant to astrochemical models. PMID- 20585685 TI - Stereoselective synthesis of ring C-hexasubstituted trianglamines. AB - The addition of organolithium reagents to the trianglimine derived from (R,R)-1,2 diaminocyclohexane and terephthalaldehyde gave the corresponding trianglamine with complete stereocontrol and the R configuration of all six newly formed stereocenters. The structure of the hexaphenyl-substituted macrocycle was determined by X-ray crystallographic study. The new trianglamines were tested as ligands in enantioselective catalytic reactions. PMID- 20585687 TI - A novel bifunctional europium complex as a potential fluorescent label for DNA detection. AB - A bifunctional europium complex of Eu(TTA)(3)(5-NH(2)-phen) using 2 thenoyltrifluoroacetonate (TTA) and 5-amino-1,10-phenanthroline (5-NH(2)-phen) as ligand reagents was applied in DNA detection assays for the first time. The complex has a long fluorescence lifetime, high fluorescence quantum yield, and is easy to label oligonucleotides for time-resolved fluorescence bioanalysis. A two probe tandem DNA hybridization assay including capture DNA(1), probe DNA(2), and target DNA(3) was employed to detect microbial pathogens. The DNA sequences in the assay were designed using software Primer Premier 5.0 based on published specific nucleotide sequences of Staphylococcus aureus and Escherichia coli. 3' Amino-modified capture DNA(1) was covalently immobilized on the common glass slide surface and the 5'-amino-modified probe DNA(2) was combined with the functionalized Eu(TTA)(3)(5-NH(2)-phen) via glutaraldehyde. The detection was done by monitoring the fluorescence intensity from the glass surface after the hybridization reaction with complementary target DNA(3). The optimal concentration of capture DNA(1) of 1.0 x 10(-6) mol l(-1) dropped onto the glass slides and optimal hybridization temperatures of 48 degrees C and 39 degrees C respectively for Staphylococcus aureus and Escherichia coli were obtained. The proposed DNA detection system showed higher sensitivity than such a complex doped nanoparticle-based detection system in our previous study for the better uniformity and dispersity of monomolecular labels. The sensing system presented a short hybridization time of 2 h, satisfactory stability, and high selectivity. The results demonstrate that this complex might be a potentially excellent dye in area of biochemical analysis. PMID- 20585688 TI - Nucleic acid G-quadruplex based label-free fluorescence turn-on potassium selective sensing. AB - We report a label-free fluorescence turn-on approach for the selective sensing of potassium. A properly selected G-rich oligonucleotide (oligo-Y) folded into stable quadruplex structure when mixed with potassium in an aqueous solution. Single-stranded nucleic acid specific nuclease was subsequently added. Since an oligonucleotide in quadruplex structure is markedly more resistant to nuclease digestion than in its random coil conformation, oligo-Y digestion by nuclease was considerably slow. On the other hand, oligo-Y mixed with other common mono- or divalent ions was completely digested in 5 min under our experimental conditions because no quadruplex or less stable quadruplex was formed. Oligo-Y in potassium was subsequently mixed with a positively charged pyrene probe. Electrostatic interactions between oligo-Y (a polyanion) and the probe induced aggregation of the probe, which in turn induced strong pyrene excimer emission. The intensity of the induced excimer emission was directly proportional to the amount of potassium added. Our method shows good sensitivity, and good selectivity against other common interference ions. PMID- 20585689 TI - Label-free selective sensing of mercury(II) via reduced aggregation of the perylene fluorescent probe. AB - In the present work, we report a fluorescence turn-on approach for the sensitive and selective detection of Hg(2+). A cationic perylene derivative (compound 1) was used as the fluorescence probe, and a thymine-rich oligonucleotide (oligo-M) was employed for the specific interaction with Hg(2+). Compound 1 shows strong tendency to self-aggregate into linear chain structures in aqueous media because of the pi-pi stacking interactions of its planar aromatic ring structure. The compound 1 free monomer is strongly fluorescent, whereas its aggregates are not fluorescent. When oligo-M and compound 1 were mixed, oligo-M induced strong compound 1 aggregation and resulted in significant fluorescence quenching. In the presence of Hg(2+), the specific interactions between oligo-M and Hg(2+) induced hairpin structure formation of oligo-M and thus weakened its binding to compound 1 aggregates. As a result, free probe monomers were released, and increased fluorescence was observed. The fluorescence intensity increase was in direct proportion to the concentration of Hg(2+) added. Our method provides a simple, fast, and efficient means for Hg(2+) quantification, it is highly sensitive with a limit of detection of 1 nM, and is also highly selective against other common metal ions. PMID- 20585690 TI - Immunosensor for the detection of cancer biomarker based on percolated graphene thin film. AB - A simple and sensitive immunosensor for the detection of cancer biomarker prostate specific antigen (PSA) has been developed. Around the percolation threshold of the graphene film, the conductivity of the graphene film varies significantly with the surface adsorption of molecules, which can be used for the detection of proteins based on antibody-antigen binding. PMID- 20585691 TI - "Clickable", polymerized liposomes as a versatile and stable platform for rapid optimization of their peripheral compositions. AB - A versatile and stable liposomal platform is developed for rapid optimization of its peripheral composition. The platform is based on polydiacetylene lipids terminated with alkynyl groups. Conditions for copper-catalyzed azide-alkyne cycloaddition (a "click" reaction) are optimized for rapid attachment of azides with controlled composition onto the liposomes. PMID- 20585692 TI - Superparamagnetic and upconversion emitting Fe3O4/NaYF4:Yb,Er hetero nanoparticles via a crosslinker anchoring strategy. AB - A crosslinker anchoring process was developed to synthesize Fe(3)O(4)/NaYF(4):Yb,Er hetero-nanoparticles (NPs) with dual properties of superparamagnetism and upconversion (UC) emission. After ligand ozonolysis treatment, these NPs could be well dispersed in water. PMID- 20585693 TI - Crystalline amidocerium(IV) oxides and a side-on bridging dioxygen complex. AB - Complexes [Ce(NR(2))(3)] (1) or [Ce(NR''(2))(3)] (2) were cerium(III) precursors to the X-ray characterised crystalline oligomeric oxygen-containing amidocerium(IV) compounds [{Ce(NR(2))(2)(mu-O)}(n)] (3, n = 2; 4, n = 3), [{Ce(NR''(2))(2)(mu-O)}(4)] (5), [{(R(2)N)(3)Ce}(2)(mu-[upper bond 1 start]OMOM[upper bond 1 end])] (6, M = Na; 7, M = K), [{(R(2)N)(3)CeOCe(NR(2))(2)}(2)(mu-[upper bond 1 start]OKOK[upper bond 1 end])] (8), and [{Ce(NR(2))(3)}(2)(mu-eta(2):eta(2)-O(2))].2C(n)H(2n+2) (9, n = 6; 9', n = 5) [R = SiMe(3), NR''(2) = TMP = [upper bond 1 start]NC(Me)(2)(CH(2))(3)C[upper bond 1 end]Me(2)]. Each was isolated in low, or for 5 very low, yield. Except for 4, the oxidising agent was O(2) at -27 degrees C in hexane (3, 6, 7, 8, 9), pentane (9'), or toluene (5), and a co-reagent for the alkali metal bis(trimethylsilyl)amido(oxy)cerate(iv)s was NaNR(2) (8) or KNR(2) (7, 8). From 1 and an equivalent portion of 2,6-(t)Bu(2)-benzoquinone after 5 weeks in pentane there was obtained the bis(amido)cyclotricer(IV)oxane 4. The NMR spectral solution chemical shifts for NR(2) groups of 3, 4, and 6-9 were consistent with each sample being diamagnetic and hence a Ce(IV) species. A transient amidocerium(IV) superoxide Ce(NR(2))(3)(eta(2)-O(2)) (J), or its TMP analogue, is considered to be the common first-formed intermediate in each case, while 4 is believed to have arisen from the adventitious hydrolysis of [{Ce(NR(2))(3)O}(2)((t)Bu(2)C(6)H(2)-1,4)]. PMID- 20585694 TI - Spiroimine shellfish poisoning (SSP) and the spirolide family of shellfish toxins: isolation, structure, biological activity and synthesis. PMID- 20585695 TI - Synthesis of functionalized resorcinols by rhodium-catalyzed [5+1] cycloaddition reaction of 3-acyloxy-1,4-enynes with CO. AB - A novel [5+1] type carbonylative cycloaddition reaction has been developed using a Rh complex as catalyst. This reaction can convert readily available 3-acyloxy 1,4-enynes and CO to a wide range of functionalized resorcinols in good yields. A mechanism involving Rh-catalyzed cyclocarbonylation of 3-acyloxy-1,4-enynes accompanied by a 1,2-acyloxy shift is proposed for the present [5+1] type cycloaddition reaction. PMID- 20585696 TI - Catalytic enantioselective synthesis of sterically demanding alcohols using di(2 degrees -alkyl)zinc prepared by the refined Charette's method. AB - A highly practical, catalytic enantioselective 2 degrees -alkyl addition to aldehydes and ketones was developed. Chiral phosphoramide ligand (1) with salt free and solvent-free di(2 degrees -alkyl)zinc reagents prepared from (2 degrees alkyl)MgCl was essential. PMID- 20585697 TI - Colloidal and optical stability of PEG-capped and phospholipid-encapsulated semiconducting polymer nanospheres in different aqueous media. AB - Aqueous dispersions of fluorescent semiconducting polymer nanospheres (SPNs) have been synthesised by two methods; miniemulsion and micellar encapsulation. The colloidal and optical stability of SPNs synthesised by these two methods has been compared in order to assess the potential of these fluorescent nanoparticles for use in biological applications. The SPNs were dispersed in water, phosphate buffer solution (PBS) and bovine serum albumin (BSA). The optical stability was studied by absorption and emission spectroscopy, and the colloidal stability was studied by dynamic light scattering (DLS) over a one month period. The results indicate that the micelle-encapsulated SPNs exhibit favourable optical and colloidal stability, and seem promising for use in biological sciences. PMID- 20585698 TI - High performance organic semiconductors for field-effect transistors. AB - The purpose of this feature article is to give an overview of recent advances in development of high performance organic semiconductors for field-effect transistors, especially those with mobility of/over amorphous silicon, since they are believed to be promising candidates with practical applications in the near future's organic electronic industry. We hope this comprehensive summary of high performance organic semiconductors will provide guidelines for the design and synthesis of novel, high performance organic field-effect semiconductors. PMID- 20585699 TI - Identification of excited-state energy transfer and relaxation pathways in the peridinin-chlorophyll complex: an ultrafast mid-infrared study. AB - The peridinin chlorophyll-a protein (PCP) is a water-soluble, trimeric light harvesting complex found in marine dinoflagellates that binds peridinin and Chl-a in an unusual stoichiometric ratio of 4:1. In this paper, the pathways of excited state energy transfer and relaxation in PCP were identified by means of femtosecond visible-pump, mid-infrared probe spectroscopy. In addition, excited state relaxation of peridinin dissolved in organic solvent (CHCl(3) and MeOH) was investigated. For peridinin in solution, the transient IR signatures of the low lying S(1) and intramolecular charge transfer (ICT) states were similar, in line with a previous ultrafast IR study. In PCP, excitation of the optically allowed S(2) state of peridinin results in ultrafast energy transfer to Chl-a, in competition with internal conversion to low-lying optically forbidden states of peridinin. After vibrational relaxation of the peridinin hot S(1) state in 150 fs, two separate low-lying peridinin singlet excited states are distinguished, assigned to an ICT state and to a slowly transferring, vibrationally relaxed S(1) state. These states exhibit different lactone bleaches, indicating that the ICT and S(1) states localize on distinct peridinins. Energy transfer from the peridinin ICT state to Chl-a constitutes the dominant energy transfer channel and occurs with a time constant of 2 ps. The peridinin S(1) state mainly decays to the ground state through internal conversion, in competition with slow energy transfer to Chl-a. The singlet excited state of Chl-a undergoes intersystem crossing (ISC) to the triplet state on the nanosecond timescale, followed by rapid triplet excitation energy transfer (TEET) from Chl-a to peridinin, whereby no Chl-a triplet is observed but rather a direct rise of the peridinin triplet. The latter contains some Chl-a features due to excitonic coupling of the pigments. The peridinin triplet state shows a lactone bleach mode at 1748 cm(-1), while that of the peridinin ICT state is located at 1745 cm(-1), indicating that the main channels of singlet and triplet energy transfer in PCP proceed through distinct peridinins. Our results are consistent with an energy transfer scheme where the ICT state mainly localizes on Per621/611 and Per623/613, the S(1) state on Per622/612 and the triplet state on Per624/614. PMID- 20585703 TI - Synthesis and properties of nano zeolitic imidazolate frameworks. AB - Nanosized zeolitic imidazolate frameworks [nZIF-8] with excellent chemical and thermal stability have been synthesized at room temperature by simple mixing of 2 methylimidazole and zinc nitrate hexahydrate in methanol/1% high molecular weight poly(diallyldimethylammonium chloride) solution for 24 h. PMID- 20585706 TI - Multidimensional nanoarchitectures based on cyclodextrins. AB - Possessing a hydrophobic cavity that can bind various organic, inorganic or biological molecules, cyclodextrins (CDs), a class of cyclic oligosaccharides with six to eight D-glucose units, are widely used as convenient and versatile building blocks in the construction of multidimensional nanoarchitectures. Through the self-assembly of CDs or their derivatives with or without templates, several kinds of CD-based one-dimensional or multidimensional nanoarchitectures, such as helix, pseudopolyrataxane, polyrotaxane, nanotube, nanowire, dendrimer, network, vesicle, nanoparticle, CD-coated carbon nanotube, and so on, can be successfully constructed via the cooperative binding of CD cavities, substituent groups, and/or template molecules. This article describes some strategies normally used to construct and characterize one-dimensional or multidimensional nanoarchitectures in solution and the solid state from various CDs and templates as building blocks. It also gives a description of the unique material and biological properties and wide applications of multidimensional CD-based nanoarchitectures. PMID- 20585707 TI - Assessment of the Multispecies Freshwater Biomonitor (MFB) in a marine context: the Green crab (Carcinus maenas) as an early warning indicator. AB - The Multispecies Freshwater Biomonitor is an online continuous biomonitor which utilises impedance conversion to quantitatively record behavioural responses of vertebrates and invertebrates to environmental change. Here, we extend the use of the MFB into the marine aquaculture environment using the Green crab (Carcinus maenas) as a biological monitor. As a ubiquitous and abundant species, C. maenas can be used in applications such as aquaculture and monitoring of diffuse and point source marine pollution. Four experiments were undertaken to establish: (1) if the electrical field generated by the apparatus had any effect on C. maenas; (2) if the behaviour of C. maenas was altered by the presence of ammonia; (3) if the behaviour of C. maenas was affected by the electrical field when ammonia was present and (4) if defined behaviours could be detected by the MFB. There was no significant effect of the current on C. maenas in the MFB. There was a significant difference in overall expression of behaviour in response to an increasing gradient of ammonia and activity of the chamber. Five behaviours, 'walking', 'climbing', 'leg stretch', 'cleaning' and 'inactivity' were detected by the MFB. C. maenas appears to be a suitable candidate for use in the MFB in a marine context. Further testing of the biomonitor and C. maenas is required using other toxicants to establish alarm thresholds that could be used in situ for water quality monitoring. PMID- 20585708 TI - Extra- and intra-articular synovial chondromatosis and malignant transformation to chondrosarcoma. AB - Intra- and extra-articular primary synovial chondromatosis (SC) was observed in a five-year-old, entire male German Shepherd. Thousands of small cartilaginous nodules were removed from the stifle joint as well as from several adjacent muscles. Diagnosis of SC was established based on clinical, radiographic and biopsy results. The owner declined to have a new surgery performed for complete nodule removal and partial synovectomy. Nine months after the initial presentation, a proximal pathological intra- articular tibial fracture was observed and malignant transformation to chondrosarcoma was diagnosed after limb amputation. No metastasis was observed after 1.5 years of follow-up. PMID- 20585709 TI - Description of the type of chemical restraint used by French veterinarians to perform hip dysplasia screening radiographs. A retrospective study based on 3302 radiographs. AB - The objective of this study was to investigate the type of chemical restraint used by French practitioners to perform official hip screening radiographs, to determine the proportion of dogs under general anesthesia versus dogs under sedation, and to search for a difference in hip dysplasia (HD) prevalence between the two groups. From September 2005 to August 2008, 3302 conventional ventrodorsal hip extended radiographs sent for official scoring to the same panellist were selected because information related to the type of chemical restraint had been provided. There were 2825 dogs under general anesthesia and 477 were sedated. Chemical restraint used by French veterinarians to perform HD screening radiographs is mainly based on general intra-venous anesthesia with an alpha2 agonist associated with ketamine. A single injection of alpha2 agonist is also mostly used for dogs which are radiographed while under sedation. A very low (1.7%) difference in HD prevalence was noted between the anesthetized and the sedated group. Except for acepromazine, which has been demonstrated to provide insufficient muscle relaxation to show evidence of hip laxity, the protocols seem acceptable as regards the Federation Cynologique Internationale requirements for HD screening. PMID- 20585710 TI - Effect of bandaging on post-operative swelling after tibial plateau levelling osteotomy. AB - OBJECTIVE: To compare the effects of bandaging on immediate postoperative swelling using a modified Robert-Jones bandage after tibial plateau levelling osteotomy (TPLO) in dogs. STUDY DESIGN: Prospective case series. METHODS: Dogs undergoing a TPLO were randomly placed into two groups. Group 1 received a modified Robert-Jones bandage postoperatively for a 24 hour period and Group 2 was not bandaged. Hindlimb circumference was measured at the level of the mid patella, the distal aspect of the tibial crest, the mid-point of the tibial diaphysis and the hock. Measurements were recorded and compared in each group preoperatively and at 24 hours and 48 hours post-operatively. Interobserver variability was compared between the two observers. RESULTS: There was no significant difference in postoperative swelling, as measured by the percentage change in circumference, between bandaged and unbandaged operated limbs after the TPLO at 24 and 48 hours at any site. Some significant differences in measurement at particular sites were observed between the two different observers, but there was a significant linear correlation at all sites between observers. The observer with the least experience consistently had slightly higher measurements at these sites. CLINICAL RELEVANCE: The use of a modified Robert-Jones bandage after TPLO did not prevent statistically significant postoperative swelling, and thus may not be indicated for this purpose. Postoperative bandages placed to control swelling after other small animal orthopaedic procedures should be evaluated individually for efficacy. PMID- 20585711 TI - Surgical treatment of a hemivertebra by partial ventral corpectomy and fusion in a Labrador puppy. AB - This report describes a partial ventral verte-brectomy and interbody fusion for a progressive hemivertebra disease using a ventral transthoracic approach in a 3.6 month-old male Labrador puppy. The goal of this article is to clarify the potential advantages of this uncommon surgical technique for this condition and to discuss its technical aspects. PMID- 20585712 TI - Longitudinal tendon tear concurrent with bilateral medial luxation of the superficial digital flexor muscle tendon in a dog. AB - Luxation of the superficial digital flexor muscle tendon (SDFMT) is a rarely reported condition in dogs, and tendon tear concurrent with SDFMT luxation had never been reported. Abnormal conformation of both calcanei and strenuous activity were suspected as contributing factors in this case. Bilateral medial SDFMT luxation was surgically treated with bursa medial incision release, redundant lateral bursa excision and apposition to the edge of the SDFMT with nonabsorbable sutures. The unilateral longitudinal tendon tear of the SDFMT associated with medial SDFMT luxation was successfully treated with horizontal mattress sutures, and a good outcome was reported for both hindlimbs. PMID- 20585713 TI - Effects of intra-articular botulinum toxin type A (Botox) in dogs with chronic osteoarthritis. AB - OBJECTIVES: To evaluate the effects of intra-articular botulinum neurotoxin type A (BoNT/A) in dogs with chronic osteo- arthritis. METHODS: Client-owned dogs with lameness and discomfort attributed to unilateral elbow or hip osteoarthritis were eligible for inclusion (n = 5). All dogs had BoNT/A (25 units) administered to the affected joint (2 elbows, 3 hips). Dogs were evaluated by pressure platform gait analysis before and at two, four, eight, and 12 weeks post-injection, and by client perception of outcome. RESULTS: In experimental limbs, ground reaction forces (peak vertical force and vertical impulse) consistently improved for a variable period of time following intra-articular BoNT/A therapy. These changes were not, however, observed in the contralateral limbs, in which values remained relatively unchanged or decreased. Four out of five owners reported at least some improvement in their dog's condition following treatment. CLINICAL SIGNIFICANCE: A multimodal approach with the intra-articular administration of BoNT/A may be an option for osteoarthritis patients that are unresponsive to medical management and unable to undergo surgery. However, the findings of this study are preliminary and must be verified by further investigation. PMID- 20585714 TI - Diagnosis and management of a fracture of the lateral trochlear ridge of the talus in a dog. AB - An eight-month-old, 31.2 kg, entire male Golden Retriever was presented for evaluation because it had a four-week history of right hindlimb lameness and audible popping occurring in association with movement of the right hindlimb. Mild right hindlimb lameness was noted upon gait analysis. Moderate to severe effusion and pain on extension were appreciated on palpation of the right tarsus. Dorsoplantar and lateral radiographs of the right tarsus revealed significant soft tissue swelling over the lateral aspect of the tarsus and widening of the joint space over the lateral trochlear ridge of the talus. A fracture of the lateral ridge was appreciated upon evaluation of the flexed dorsoplantar view. Un enhanced computed tomography of the right tarsus confirmed fracture of the talus; one large and two small bone fragments were noted adjacent to the lateral aspect of the lateral trochlear ridge and medial to the fibula. The fracture was surgically repaired via a lateral approach; a fibular osteotomy was performed. The fragment was manually reduced and secured with a 1.5 mm cortical screw placed in lag fashion. The fibular osteotomy site was reduced and fixed with two 1.6 mm Kirshner wires and a tension band composed of 0.9 mm cerclage wire. The patient made a complete clinical recovery, however, the union was fibrous and evidence of mild osteo- arthritis was noted on postoperative radiographs. PMID- 20585715 TI - A surgical tendonitis model in horses: technique, clinical, ultrasonographic and histological characterisation. AB - OBJECTIVE: Tendon injuries are common in all athletic activities in both humans and horses. Research of treatment modalities for this disease has typically been performed on a model of collagenase-induced tendonitis. This model has several disadvantages. Our hypothesis was that a reproducible core lesion could be created surgically in superficial digital flexor tendons (SDFT), which could then be evaluated consistently using ultrasonography. MATERIALS AND METHODS: Four horses free of forelimb lameness were used in this study. Each horse underwent general anaesthesia and a synovial resector was used to create a core lesion in the SDFT of each forelimb. Sonographic examination was conducted weekly using 2 cm intervals between a section 7 and 25 cm distal to the accessory carpal bone. At two, four, eight, and 12 weeks after injury, a horse was euthanatized. Histopathological evaluation of the SDFT was performed at the same levels as the sonographic examination. RESULTS: Only mild clinical signs of tendonitis were observed. Ultrasonographic core lesions were 10-16 cm long and had a mean maximum cross-sectional area (CSA) of 18.25 +/- 5.91% occurring at 17-23 cm distal to the accessory carpal bone, and a mean volume of 1.86 +/- 0.26 cm(3). Mean duration taken to achieve maximum lesion CSA and lesion volume was 35 +/- 7 days. Histologically, the lesions were characterised by mild inflammation followed by fibroplasia. CONCLUSION: The reported surgical technique resulted in core lesions that were consistent in size and location, were readily evaluated with ultrasonography, and showed similarities with the ultrasonographic and histological progression of naturally occurring tendonitis lesions. PMID- 20585716 TI - A review of the human and veterinary literature on local anaesthetics and their intra-articular use. Relevant information for lameness diagnosis in the dog. AB - Lameness in dogs is often a diagnostic challenge. In many cases it is difficult to determine the exact localisation of lameness because of the absence of palpable changes, or because of unreliable pain response due to high pain tolerance, stress or aggression of the dog. In horses and humans, intra-articular administration of local anaesthetics is commonly used for diagnostic purposes. In this review, information from human and veterinary studies on different local anaesthetic agents and their application for diagnostic intra-articular anaesthesia is given. Based on this information, a protocol for diagnostic intra articular anaesthesia in the dog can be developed and evaluated in future studies. PMID- 20585717 TI - Fixin internal fixator: concept and technique. AB - This report describes the Fixin internal fixator system(a), a fracture fixation device characterised by a locking conical coupling between screw heads and titanium alloy inserts that are screwed into a stainless steel plate construct. The mechanical principles, implants, instruments and surgical technique are discussed. PMID- 20585718 TI - Torsion of the urinary bladder after pelvic trauma and surgical fixation. AB - Urinary bladder torsion in a dog was successfully treated with reduction of the torsion and cystopexy. Urinary bladder torsion is a rare occurrence in dogs and has only been reported once previously. In the previous report, the bladder torsion was iatrogenic. This brief communication describes a case of bladder torsion and subtotal necrosis following reduction and stabilisation of pelvic fractures sustained during a road traffic accident. Proposed aetiology, diagnosis, treatment and postoperative management are discussed. PMID- 20585719 TI - Chondrosarcoma in the humerus of a goat. AB - The clinical, radiographical and histo-pathological findings of a chondrosarcoma in the humerus of a goat are discussed. An 11-year-old female Saanen goat was admitted for evaluation of chronic, progressive left forelimb lameness. Clinical examination revealed signs of pain in the shoulder region. Radiographs of the scapulohumeral joint showed a large lytic lesion of the proximal third of the humerus with cortical destruction, intralesional calcification and marked periosteal reactions. Differential diagnoses included aggressive bone lesions as seen with osteomyelitis or a primary bone tumour, such as osteosarcoma, chondrosarcoma or fibrosarcoma. The goat was euthanatized for humane reasons because of the poor prognosis. On the basis of the histopathological findings, the lesion was diagnosed as grade II chondrosarcoma. The tumour had already spread to the lungs and the left prescapular lymph node at the time of diagnosis. PMID- 20585720 TI - Treatment of lumbosacral discospondylitis by surgical stabilisation and application of a gentamicin-impregnated collagen sponge. AB - This report describes a case of lumbosacral discospondylitis in a two-year-old boxer dog. The dog had been presented with chronic hindlimb lameness and signs of lumbar spinal pain. The diagnosis was confirmed with a magnetic resonance imaging scan and positive blood culture. Following unsuccessful conservative management, the dog was treated with surgical stabilisation using screws and polymethylmethacrylate, and implantation of a gentamicin-impregnated collagen sponge into the L7-S1 disc space. This technique has not previously been described. The dog had a successful long-term outcome with complete resolution of clinical signs. PMID- 20585722 TI - Obesity is undoubtedly one of the most pressing public health problems in Mexico. PMID- 20585723 TI - Metabolic syndrome in Mexican adults: results from the National Health and Nutrition Survey 2006. AB - OBJECTIVE: To examine the prevalence of metabolic syndrome (MS) and its associated risk factors in Mexican adults aged 20 years or older, using data derived from the National Health and Nutrition Survey 2006 (ENSANUT 2006). MATERIAL AND METHODS: The ENSANUT 2006 was conducted between October 2005 and May 2006. Questionnaires were administered to 45 446 adult subjects aged 20 years or older who were residents from urban and rural areas. Anthropometric and blood pressure measurements were obtained from all subjects and fasting blood specimens were provided by 30% of participants. We randomly selected a sub-sample of 6 613 from which laboratory measurements were carried out for glucose, insulin, triglycerides, total cholesterol and HDL-cholesterol. For this analysis, we included only results from eight or more hours of fasting samples (n=6 021). We used individual weighted factors in the statistical analysis and considered the survey's complex sampling design to obtain variances and confidence intervals. All analyses were done using SPSS 15.0. RESULTS: In accordance with definitions by the National Cholesterol Education Program Adult Treatment Panel III (ATP III), the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), and the International Diabetes Federation (IDF), the prevalence of MS in Mexican adults aged 20 years or older was 36.8, 41.6 and 49.8%, respectively. Women were more affected than men due to the higher prevalence of central obesity among females. Prevalence of MS increased with age and was higher among populations living in metropolitan areas, in the west-central region, and those with lower education. DISCUSSION: Regardless of the MS definition, a large proportion of Mexican adults has the condition, so preventive measures are needed to decrease the prevalence of the MS components in this population. MS can predict type 2 diabetes and cardiovascular disease, two of the main causes of death in the adult population in Mexico. The intentional search of MS components allows stratifying the population according to risk levels. Treatment for each component should be implemented properly to prevent or delay onset of type 2 diabetes and cardiovascular disease. PMID- 20585724 TI - Prevalence and distribution of type 2 diabetes mellitus in Mexican adult population: a probabilistic survey. AB - OBJECTIVE: To describe the prevalence, distribution and degree of control of type 2 diabetes (T2D) in Mexican population. MATERIAL AND METHODS: Subjects were classified as previously diagnosed T2D (PD); or as "finding of the survey" (FS) (glucose >or=126 mg/dL). Hemoglobin A1c was measured in PD-subjects. RESULTS: The prevalence for PD-T2D was 7.34% (95%CI 6.3, 8.5) and for FS 7.07% (95%CI 6.1, 8.1), summing 14.42%; (7.3 million diabetics). 5.3% of PD-T2D were in good, 38.4% in poor and 56.2% very poor control. Older age (OR=0.96, 95%CI 0.94, 0.97), lower BMI (OR=0.95, 95%CI 0.91, 1.0), were protective for poor control. Affiliation to private services (OR=1.77, 95%CI 0.98, 3.13), larger T2D duration (OR=1.05, 95%CI 1.01, 1.08), and combining oral medication and insulin (OR=16.1, 95%CI 1.61, 161) were riskier. CONCLUSIONS: We found an alarming prevalence of T2D in Mexican population; the majority of PD diabetics are in poor control. Research on the latter is warranted. PMID- 20585725 TI - The status of non-transmissible chronic disease in Mexico based on the National Health and Nutrition Survey 2006. Introduction. PMID- 20585726 TI - Early-onset type 2 diabetes in a Mexican survey: results from the National Health and Nutrition Survey 2006. AB - OBJECTIVE: To describe the characteristics of patients with type 2 diabetes diagnosed before age 40 (early-onset type 2 diabetes) identified in a nation wide, population-based study. MATERIALS AND METHODS: The survey was done in Mexico during 2006. Medical history, anthropometric and biochemical measurements were obtained in every subject. RESULTS: Cases diagnosed before (n=181) and after age 40 (n=659) were included. Early-onset type 2 diabetes was present in 13.1% of the previously diagnosed, 30.3% of the cases identified during the survey and 21.5% of the whole population with diabetes. These individuals had a greater prevalence of obesity and hypertriglyceridemia compared to the cases diagnosed after age 40. CONCLUSIONS: Early-onset type 2 diabetes was present in 21.5 % of patients with type 2 diabetes in Mexico. Close to 70% of them were obese or overweight and had the clinical profile of the metabolic syndrome. PMID- 20585727 TI - The status of diabetes care in Mexican population: are we making a difference? Results of the National Health and Nutrition Survey 2006. AB - OBJECTIVE: Examine clinical indicators to evaluate diabetes care in Mexico. MATERIAL AND METHODS: Diabetics (self reported, with therapy) were examined with standardized questionnaires, anthropometry, glucose, lipids and glycohemoglobin. Data were analyzed statistically. RESULTS: There were 2 644 patients, 677 cases without access to medical care (73% women), most lived in rural communities and spoke aboriginal dialect. Prevalence of obesity for private access group was 21.2%, for other or non access group was between 31 and 65%. The group without or basic education was most common, 76% of the cases had HDL <40 mg/dl and 36% had hypertriglyceridemia. Only 6.6% of patients had HbA1c <7%. There was no significant difference between HbA1c values observed in the group with or without access. Most patients were treated with oral agents. A significant group was without therapy. Assessments for complications was infrequent. CONCLUSIONS: Current model for diabetes care in Mexico is inefficacious and a paradigm change is necessary. PMID- 20585728 TI - Methodology for the analysis of type 2 diabetes, metabolic syndrome and cardiovascular disease risk indicators in the ENSANUT 2006. AB - OBJECTIVE: To describe: a) the methods used to quantify biochemical indicators of Type 2 Diabetes (T2D), and other cardiovascular risk indicators in the Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006) and b) compare the sub sample with the non-selected participants in diverse socio-demographic, anthropometric and health characteristics. MATERIAL AND METHODS: A sub-sample of 6 021 fasting adult participants was randomly selected from the total fasting participants (n=39 425). We compared diverse socio-demographic, anthropometric and health parameters between this sub-sample and the rest of the participants. RESULTS: No differences were found in sociodemographics characteristics, except age, between the sub-sample and from the rest of the fasting adults. In addition no difference were found between prevalences of overweight and obesity, central obesity, and previously diagnosed high blood pressure, T2D or hypertrigliceridemia. CONCLUSIONS: The randomly selected sub-sample was not essentially different from the rest of the fasting subjects. Thus, no bias is expected in the interpretation of cardiovascular risk indicators derived from these data. PMID- 20585729 TI - Prevalence of dyslipidemias in the Mexican National Health and Nutrition Survey 2006. AB - OBJECTIVE: To describe the prevalence of lipid abnormalities found in the Mexican National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS: Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9- to 12-hour fast. RESULTS: Median lipid concentrations were: cholesterol 198.5 mg/dl, triglycerides 139.6 mg/dl, HDL-cholesterol 39.0 mg/dl, non-HDL-cholesterol 159.5 mg/dl and LDL-cholesterol 131.5 mg/dl. The most frequent abnormality was HDL-cholesterol below 40 mg/dl with a prevalence of 60.5% (95%CI 58.2-62.8%). Hypercholesterolemia (> 200 mg/dl) had a frequency of abnormality of 43.6% (95%CI 41.4-46.0%). Only 8.6% of the hypercholesterolemic subjects knew their diagnosis. Hypertriglyceridemia (>or= 150 mg/dl) was observed in 31.5% (IC 95% 29.3-33.9%) of the population. CONCLUSIONS: The ENSANUT 2006 data confirm that the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high. PMID- 20585730 TI - Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system. AB - OBJECTIVE: To estimate the percentage of Mexican adults that may require lipid lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). MATERIAL AND METHODS: Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. RESULTS: A cardiovascular risk equivalent was found in 13.8% and >or=2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >or=2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. CONCLUSIONS: Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%). PMID- 20585731 TI - Hypertension in Mexican adults: results from the National Health and Nutrition Survey 2006. AB - OBJECTIVE: To describe the prevalence of hypertension among Mexican adults, and to compare to that observed among Mexican-Americans living in the US. MATERIAL AND METHOD: The primary data source came from adults (>20 years) sampled (n=33366) in the Mexican National Health and Nutrition Survey 2006 (ENSANUT 2006). Hypertension was defined when systolic blood pressure was >or=140 and/or diastolic was >or= 90 or patients previously diagnosed. RESULTS: A total of 43.2% of participants were classified as having hypertension. We found a positive statistically significant association (p<0.05) between hypertension and BMI, abdominal obesity, previous diagnosis of diabetes and hypercholesterolemia. Subjects with hypertension had a significantly higher odd of having a history of diabetes or hypercholesterolemia. Hypertension had a higher prevalence in Mexico than among Mexican-Americans living in the US. CONCLUSIONS: Hypertension is one of the most prevalent chronic diseases in Mexico. In the last six years in Mexico, a substantial increase (25%) has been observed in contrast to the reduction seen among Mexican-Americans (-15%). PMID- 20585732 TI - Trends for type 2 diabetes and other cardiovascular risk factors in Mexico from 1993-2006. AB - OBJECTIVE: To describe the trends in the prevalence of type 2 diabetes (T2D), and other cardiovascular risk factors in three national health surveys (1993, 2000 and 2006). MATERIALS AND METHODS: The databases of three surveys: ENEC 1993, ENSA 2000 and ENSANUT 2006 were gathered. Calculations of published data were reprocessed to do appropriate adjustments to assure comparability among surveys. RESULTS: From 1993 to 2006 the prevalence of type 2 diabetes (6.7-14.4%), metabolic syndrome (26.6-36.8%), hypertension (23.8-30.7%), hypercholesterolemia (27-43.6%), and high LDL-cholesterol (31.6-46%) increased rapidly. The prevalence of low HDL cholesterol was very high (60.5-63%) in all surveys and remained remarkably unchanged among surveys. CONCLUSIONS: This increasing trends for the prevalence of T2D and cardiovascular risk factors predicts larger increments in the near future for T2D and cardiovascular morbidity and mortality. Intensification of the preventive and remedy strategies is mandatory in order curve the foreseen dramatic increment in the disease burden. PMID- 20585733 TI - And now what? Time for daring innovation. PMID- 20585734 TI - Evaluation of the musculoskeletal system of patients in cardiopulmonary and metabolic rehabilitation programs. AB - BACKGROUND: Participants of cardiopulmonary and metabolic rehabilitation (CPMR) programs may present with musculoskeletal changes that may affect treatment compliance and effectiveness. OBJECTIVE: To develop an instrument for evaluation of the musculoskeletal system and identification of problems, especially those related to exercise, so that patients can be cleared to exercise with no restrictions, cleared with restrictions, or not cleared before approval from a specialist. METHODS: Construction and validation (according to Cronbach's alpha) of a musculoskeletal system assessment inventory (MSSAI), for subsequent administration to participants in CPMR programs. RESULTS: A total of 103 individuals participating in CPMR programs were evaluated by means of the MSSAI, whose internal validity and reliability proved to be satisfactory. Of these, 33 were men (32%) and 70 were women (68%), with age ranging from 36 to 84 years; 47 (45.6%) had already been diagnosed with musculoskeletal system disorders; 39 (37.9%) had already received specific treatment for the musculoskeletal system; 33 (32%) used to take medications to relieve symptoms related to the musculoskeletal system; and 10 (9.7%) had a medical restriction for performing some type of exercise. We should point out that 48 individuals (46.6%) reported pain in the musculoskeletal system; in 14 (13.6%) of them, the pain worsened by exercise, and this should have prevented them from participating in exercise programs before receiving approval from a specialist. CONCLUSION: The MSSAI, whose internal validity and reliability proved satisfactory, showed that there was some restriction to exercise practice for almost half of the individuals participating in CPMR programs, and that some of them should not have been cleared without approval from a specialist. PMID- 20585735 TI - Effect of diet and indoor cycling on body composition and serum lipid. AB - BACKGROUND: Indoor cycling is an aerobic exercise that employs large muscle groups of the lower limbs, lacking osteoarticular impact and high energy expenditure, which makes it interesting to generate a non-pharmacological strategy. OBJECTIVE: To assess body composition and lipid profile in overweight women after twelve weeks of low-calorie diet and indoor cycling training. METHODS: We randomly assigned 40 women (23.90 +/- 3.10 years), divided into four groups: control (C), indoor cycling (CI), indoor cycling combined with low calorie diet (CD) and low-calorie diet (D). The variables were: height and body mass, BMI, fat percentage, lean body mass, triglycerides, cholesterol and lipoproteins (HDL, LDL, VLDL). The indoor cycling training consisted of three weekly sessions of 45 minutes each and an energy restriction of about 1,200 kcal. The study lasted 12 weeks. We used descriptive statistics (mean and standard deviation) and inferential statistics (Student's t test). The level of significance was p < 0.05. RESULTS: The groups CI, CD and D significantly reduced the mean anthropometric variables after 12 weeks of intervention (body mass, fat percentage and body mass index), and serum levels of total cholesterol and triglycerides. HDL cholesterol increased significantly for groups CI and CD. CONCLUSION: According to the results, the indoor cycling and the low-calorie diet helped fight overweight and control serum lipids. PMID- 20585736 TI - Effects of the corticosteroids in the lesions by radiofrequency on rats' thigh in different age groups. AB - BACKGROUND: The corticosteroids limit the late growth of the lesions by radiofrequency (RF) on the rats' infants' thighs, but the effects on the pubescent and adult rats are unknown. OBJECTIVE: Evaluate the effects of the corticosteroids in the healing of the lesions by RF on the rats' thighs muscles in different age groups. METHODS: Ablation was performed on the thigh muscle of 30 rats (1 lesion per animal): infants (30 days old, weight 73 g, n = 10), pubescents (60 days old, weight 230 g, n = 10) and 10 adults (90 days old, 310 g, n = 10), subdivided in control and treated groups, that received Hydrocortisone (10 mg/kg IM post-RF) and Betametasone (3.5 mg/kg IM, twice a week, for 29 days). The rats were sacrificed 60 days after the ablation for hystopathological and planimetric analysis with specified software (ImageJ). RESULTS: In the infant, pubescent and adult groups, the weight gain in the follow up did not differ between the control and the treated ones. In the control group, the lesions of the infants and pubescents were superior (p = 0.01) to the adults'. The treatment reduced the size of the lesion in the infants (5.58+0.61 mm2 vs 4.02+0.23 mm(2); p < 0.01) and pubescents (5.20+0.47 mm(2) vs 4.16+0.48 mm(2); p < 0.01), but not in the adults (4.44+0.50 mm(2) vs 4.79+0.53 mm(2), p = NS). Infant and pubescent treated groups presented lower collagen deposition and less fibrotic bands invading the healthy tissue from the central fibrosis area, and forming lesions with remarkably more reduced dimensions than their controls. There were no differences in the adult groups. CONCLUSION: The corticosteroids seem to reduce the late growth of lesion, in addition to attenuate the fibrotic proliferation in the infant and pubescent rats. PMID- 20585737 TI - Effectiveness and safety of drug-eluting stents in a cardiology clinic in Curitiba, PR, Brazil. AB - BACKGROUND: The effectiveness and safety of drug-eluting stents (DES) have still been questioned. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of these stents, as well as the incidence of target lesion revascularization (TLR), in addition to identifying possible variables influencing the need for TLR. METHODS: A total of 203 patients from Hospital Costantini who were clinically followed up for one to 3 years were selected. RESULTS: The sample characteristics were as follows: 470 lesions; 171 (84.24%) male patients; 54 (26.6%) had diabetes; 131 (64.35%) had hypertension; 127 (62.56%), dyslipidemia; 40 (19.70%) were smokers; and 79 (38.92%) had a family history of coronary artery disease. Also: 49 (24.14%) patients presented with stable angina; 58 (28.57%), unstable angina; and 6 (2.96%), myocardial infarction. Eighty five (41.87%) patients were asymptomatic, and 146 (71.92%), had multivessel disease. As for the characteristics of the lesions, 77.45% were B2/C (AHA/ACC). Taxus was implanted in 73.62% of the patients. Stents with diameter > 2.5 mm were used in 381 (81.96%) patients. The stent length was < 30 mm in 67.87% of the lesions, with a mean of 2.3 stents per patient. After follow up, 19 patients (9.3%) underwent TLR. Four patients died (1.97%), two of them of MI (0.98%), one of stroke (0.49%), and one of abdominal aneurysm (0.49%). Also, one patient died of late thrombosis (0.49%), and one of reinfarction (0.49%). In the statistical analysis carried out, only the bifurcation lesions variable reached values close to the statistical significance level, with p < 0.06. CONCLUSION: In conclusion, drug-eluting stents have good effectiveness and safety profiles; the incidence of TLR was 9.3%, and we did not identify a variable correlated with the need for TLR. PMID- 20585738 TI - Geometric indexes of heart rate variability in obese and eutrophic children. AB - BACKGROUND: Obesity causes changes in cardiac autonomic modulation. OBJECTIVE: To investigate the autonomic modulation of eutrophic and obese children by means of indexes of heart rate variability (HRV) obtained through geometric methods. METHODS: We analyzed data from 133 children aged 8 to 13, divided into two groups: obese (n = 61) and eutrophic (n = 72) according to body mass index for age and sex. For the analysis of HRV, heart rate was recorded beat-to-beat. The RR intervals were transformed into geometric figures, and from them, we calculated the triangular index (RRtri), triangular interpolation of RR intervals (TINN), the indexes SD1, SD2 and SD1/SD2 ratio, obtained from the Poincare plot. Visual analysis of the plot was also performed. Student's t test was performed for unpaired data and Mann-Whitney's test, with significance level of 5.0%, for data analysis. RESULTS: In obese children, RRtri indexes were proven to be reduced (0.0730 vs 0.1084 [median]), TINN (171.80 +/- 55.08 vs 218.26 +/- 51.12), SD1 (19.93 +/- 9.10 vs 24.10 +/- 8.03) and SD2 (51.63 +/- 16.53 vs 69.78 +/- 17.19). The SD1/SD2 ratio showed no significant differences (0.3781 +/- 0.12 vs 0.3467 +/- 0.08). Visual analysis of the plot, in obese children, revealed a smaller dispersion of RR intervals both beat-to-beat, and in the long term, indicating lower HRV. CONCLUSION: Obese children presented changes in the autonomic nervous system characterized by decreases in parasympathetic activity and overall variability. PMID- 20585739 TI - Gastric lavage in the diagnosis of pulmonary tuberculosis in children: a systematic review. AB - OBJECTIVE: To analyze standardization of gastric lavage protocols in the diagnosis of pulmonary tuberculosis in children. METHODS: A systematic review was conducted for the period between 1968 and 2008 in the following databases: LILACS, SCIELO and MEDLINE. The search strategy included the following terms: "gastric lavage and tuberculosis" or "gastric washing and tuberculosis" with the restriction of "children aged up to 15 years;" "gastric lavage and tuberculosis and childhood" or "gastric washing and tuberculosis and childhood." There were retrieved 80 articles and their analysis was based on information on the gastric lavage protocol for the diagnosis of pulmonary tuberculosis in children: preparation of children and fasting; time of gastric aspiration; aspiration of gastric residues; total volume of aspirate; solution used for aspiration of gastric contents; decontaminant solution; buffer solution; and time for forwarding samples to the laboratory. After a thorough analysis, 14 articles were selected. RESULTS: No article detailed the whole procedure. Some articles had missing information on: amount of gastric aspirate; aspiration before or after solution injection; solution used for gastric aspiration; buffer solution used; and waiting time between specimen collection and laboratory processing. These results showed inconsistencies of gastric lavage protocols. CONCLUSIONS: Although gastric lavage is a secondary diagnostic approach used only in special cases that did not reach the diagnostic scoring as recommended by the Brazilian Ministry of Health, there is a need to standardize gastric lavage protocols for the diagnosis of pulmonary tuberculosis in children. PMID- 20585740 TI - User embracement and maternal characteristics associated with liquid offer to infants. AB - OBJECTIVE: To identify the maternal characteristics and welcoming actions towards mothers of infants aged less than six months associated with early liquid offer. METHODS: Cross-sectional study performed in 2007, with a representative sample of mothers of infants aged less than six months (n=1,057), users of Primary Health Care (PHC) Units, in the city of Rio de Janeiro, Southeastern Brazil. A multivariate logistic regression model was used to estimate the association between explanatory variables and liquid offer, with weighing and design effect and controlled for infant age. RESULTS: Of all mothers, 32% did not receive the welcoming card in the maternity hospital, 47% did not receive guidance on breastfeeding at their first visit to the PHC unit after childbirth and 55% reported they had offered liquids to their infants. Women without at least six months of previous breastfeeding experience were more likely to offer liquids than those with such experience (OR=1.57; 95% CI: 1.16;2.13). Mothers who had not received guidance on breastfeeding at their first visit to the UBS after childbirth were 58% more likely to offer liquids than those who had received it. Liquid offer was positively associated with adolescence among women with a partner (OR=2.17; 95% CI: 1.10;4.30) and negatively associated with adolescence among those without a partner (OR=0.31; 95% CI: 0.11;0.85). Among women with less than eight years of education, those who had not received guidance on breastfeeding after childbirth were 1.8 times more likely to offer liquids than others who had received it. CONCLUSIONS: Age, marital status and previous breastfeeding experience are maternal characteristics associated with liquid offer to infants aged less than six months. Receiving early guidance on breastfeeding could reduce liquid offer to infants. PMID- 20585741 TI - Medicine prices and availability in the Brazilian Popular Pharmacy Program. AB - OBJECTIVE: To analyze the performance of the Programa Farmacia Popular do Brasil (FPB - Brazilian Popular Pharmacy Program) in the public and private sectors, in terms of availability and cost of medicines for hypertension and diabetes. METHODS: The methodology developed by the World Health Organization, in partnership with the Health Action International, was used to compare medicines prices and availability. This study was performed in May 2007, in different sectors (public, private and the Program's government-managed [FPB-P] and private sector-managed [FPB-E] categories), in 30 cities in Brazil. A total of four medicines were analyzed: captopril 25mg and hydrochlorothiazide 25mg for hypertension; and metformin 500mg and glibenclamide 5mg for diabetes. RESULTS: FPB-E showed greatest medicine availability, while the public sector the lowest. The percentage of availability of similar medicines was higher than that of generic medicines, both in the public sector and in the FPB-P. Comparison of prices among sectors showed a lower purchase price in the FPB-E, followed by the FPB-P. The FPB-E charged prices that were over 90% cheaper than those in the private sector. The number of working days required to obtain treatment for hypertension and diabetes were fewer in the FPB-E. CONCLUSIONS: The lower availability found in the public sector could be one of the reasons for the migration of users from the public sector to the FPB. The high prices in the private sector also contribute for this Program to be an alternative of medicine access in Brazil. PMID- 20585742 TI - Beyond the income inequality hypothesis and human health: a worldwide exploration. AB - OBJECTIVE: To analyze whether the relationship between income inequality and human health is mediated through social capital, and whether political regime determines differences in income inequality and social capital among countries. METHODS: Path analysis of cross sectional ecological data from 110 countries. Life expectancy at birth was the outcome variable, and income inequality (measured by the Gini coefficient), social capital (measured by the Corruption Perceptions Index or generalized trust), and political regime (measured by the Index of Freedom) were the predictor variables. Corruption Perceptions Index (an indirect indicator of social capital) was used to include more developing countries in the analysis. The correlation between Gini coefficient and predictor variables was calculated using Spearman's coefficients. The path analysis was designed to assess the effect of income inequality, social capital proxies and political regime on life expectancy. RESULTS: The path coefficients suggest that income inequality has a greater direct effect on life expectancy at birth than through social capital. Political regime acts on life expectancy at birth through income inequality. CONCLUSIONS: Income inequality and social capital have direct effects on life expectancy at birth. The "class/welfare regime model" can be useful for understanding social and health inequalities between countries, whereas the "income inequality hypothesis" which is only a partial approach is especially useful for analyzing differences within countries. PMID- 20585743 TI - The paradox of age: an analysis of responses by aging Brazilians to International Affective Picture System (IAPS). AB - OBJECTIVE: To explore the possible differences in subjective analysis of the emotional stimuli from the International Affective Picture System between elderly and young samples. METHOD: 187 elderly subjects ranked the International Affective Picture System images according to the directions from the Manual of Affective Ratings. Their scores were compared to those obtained from International Affective Picture System studies with young people. RESULT: There is an age-related difference in arousal and valence in the International Affective Picture System rating. The correlation between affective valence and arousal is strong, and negative for the elderly. The expected versus the observed frequency of International Affective Picture System images between elderly and young samples show a statistical difference. CONCLUSION: This study shows an inter-age statistical dichotomy in how elderly and young people subjectively evaluate International Affective Picture System images. PMID- 20585744 TI - [Brazilian guidelines for the diagnosis of narcolepsy]. AB - This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy. PMID- 20585745 TI - Unconventional sexual behaviors and their associations with physical, mental and sexual health parameters: a study in 18 large Brazilian cities. AB - OBJECTIVE: There have been many studies investigating paraphilias and sexual compulsion, but thus far little data about prevalence of unusual sexual practices that are subthreshold for these diagnoses. The associations between unconventional sexual behavior and sociodemographic and health parameters were investigated. METHOD: A cross-sectional study of 7,022 individuals (45.4% of women) was carried out using a self-administered questionnaire that compared individuals carrying at least one reference of unconventional sexual behavior (group 1) with individuals without such reference (group 2). RESULTS: Women's mean age was 35.0 vs. 35.9 years (p < 0.05) and men's mean age was 36.5 vs. 37.8 years (p < 0.05) being lower in group 1 than in group 2, respectively. More men (52.3%) than women (30.4%) (p < 0.001) presented unconventional sexual behavior. Fetishism (13.4%) and voyeuristic behavior (13.0%) were more frequent. Unconventional sexual behavior was associated with male gender, single or separated marital status, black or mulatto race, elementary and high school educational level, history of posttraumatic stress disorder treatment, alcohol dependence, emergency contraception, difficulty at the beginning of sexual life, sexual violence, bisexuality, and performance of anal or oral intercourse. CONCLUSION: Unconventional sexual behaviors are important because they are associated with poorer health status and lower educational levels. PMID- 20585746 TI - [Biologics. New drugs, new adverse reactions]. AB - Biologics have been available in Germany for the treatment of moderate to severe chronic plaque psoriasis and/or psoriatic arthritis since 2004. They include chimeric (human/mouse) or fully human monoclonal antibodies or recombinant fusion proteins. The currently available biologics are cytokine antagonists, which neutralize either TNF-alpha or the interleukins IL-12 and IL-23. Unexpected adverse events result either from their potential immunogenicity or from their mode of action, which consists in neutralizing the biologic activity of the respective cytokines. In particular the increased risk for severe infections that may take an atypical course during biologic therapy deserves attention in daily clinical practice. PMID- 20585747 TI - [Hysteria I. Histrionic personality disorder. A psychotherapeutic challenge]. AB - What is left of Freud's hysteria in modern diagnostics is the histrionic personality. Psychological and somatic functional disorders, such as dissociative and somatoform disorders are freed from the label of being hysterical, but even the histrionic personality disorder does not enjoy professional agreement as far as diagnostics and therapy are concerned. This disorder is characterized by dramatization, suggestibility, superficial changing affects, impressionist cognitive style, preoccupation with outward appearance, seductive behavior and the wish to take centre stage, a compensatory attitude resulting from important childhood relationships. A comorbidity with narcissistic and antisocial personality exists and also with ADHS. PMID- 20585748 TI - [Evidence-based standards for care of patients with dementia. The interdisciplinary S3 guideline for dementia]. PMID- 20585749 TI - Development of EST-PCR markers for Thinopyrum intermedium chromosome 2Ai#2 and their application in characterization of novel wheat-grass recombinants. AB - A series of expressed sequence tags-derived polymerase chain reaction (EST-PCR) markers specific to chromosome 2Ai#2 from Thinopyrum intermedium were developed in this study using a new integrative approach. The target alien chromosome confers high resistance to barley yellow dwarf virus (BYDV), which is a severe virus disease in wheat. To generate markers evenly distributed on 2Ai#2, a total of 105 primer pairs were designed based on mapped ESTs from 8 bins of wheat chromosome 2B with intron-prediction by aligning ESTs with genomic sequences of the new model plant Brachypodium distachyon. Eight and seven polymorphic markers on the short arm and the long arm of chromosome 2Ai#2, respectively, were obtained with a polymorphism rate of 14.3%. These chromosome 2Ai#2-specific EST PCR markers were then used in tracing and exploring the structural variation of the alien chromosome in the population derived from the immature embryo culture of the cross between N452, a 2Ai#2(2D) substitution line, and common wheat CB037. Two centric fusion of translocations involving 2Ai#2 short or long arm with wheat chromosome 2D and some new genetic stocks including telosomes with the alien chromosome short or long arm were identified in the SC(3) generations, which provided basic materials to further study the mechanism of the BYDV resistance. BYDV tests in two field seasons suggest that the BYDV resistance was mainly conferred by the short arm, gene interaction on both arms of the alien chromosome was discussed. PMID- 20585751 TI - Total mercury in fish, sediments and soil from the River Pra Basin, southwestern Ghana. AB - Total Mercury (Hg) concentrations were determined in soil, river sediments and six (6) species of fish from the River Pra Basin in southwestern Ghana by Cold Vapour Atomic Absorption Spectrometry. Mercury concentration (microg g(-1)) ranged from 0.042 to 0.145 for soil: from 0.390 to 0.707 for sediments and from <0.001 to 0.370 for fish. All the fish samples had Hg concentration below the World Health Organisation (WHO) permissible limit of 0.5 microg g(-1) whereas all the sediment samples had levels higher than the US-EPA value of 0.2 microg g(-1). The results obtained from this study showed that fish from River Pra Basin are unlikely to constitute any significant mercury exposure to the public through consumption. No apparent trend of increasing mercury concentration along the main river as it flows downward toward the sea was observed. PMID- 20585750 TI - Location of major effect genes in sorghum (Sorghum bicolor (L.) Moench). AB - Major effect genes are often used for germplasm identification, for diversity analyses and as selection targets in breeding. To date, only a few morphological characters have been mapped as major effect genes across a range of genetic linkage maps based on different types of molecular markers in sorghum (Sorghum bicolor (L.) Moench). This study aims to integrate all available previously mapped major effect genes onto a complete genome map, linked to the whole genome sequence, allowing sorghum breeders and researchers to link this information to QTL studies and to be aware of the consequences of selection for major genes. This provides new opportunities for breeders to take advantage of readily scorable morphological traits and to develop more effective breeding strategies. We also provide examples of the impact of selection for major effect genes on quantitative traits in sorghum. The concepts described in this paper have particular application to breeding programmes in developing countries where molecular markers are expensive or impossible to access. PMID- 20585752 TI - Determination of organochlorine pesticides residues in human adipose tissue, data from Cukurova, Turkey. AB - We determined and compared the levels of BHC and DDT isomers and metabolites and HCB in the adipose tissue of 82 cases of autopsies performed at the Morgue Department of Adana Branch of the Council of Forensic Medicine. The relationships between the age, gender, and body mass indexes of cases, and the accumulation of OCs residues were also investigated. Detectable concentrations of p,p'-DDE were found in 100% of adipose tissue samples. Concentrations of OCs in female adipose tissues were significantly higher than male adipose tissues (p < 0.05). The presented work is highly significant, being the first study pointing out the chronic exposure to organochlorine pesticides in Cukurova region. PMID- 20585753 TI - Seasonal variations in the concentrations of metals in Crassostrea corteziensis from Sonora, Mexico. AB - This study examines seasonal variations in the concentrations of Cd, Cu, Pb, and Hg in experimentally cultured Crassostrea corteziensis, an oyster species known to have high resistance to physical and chemical stressors. The highest levels of Cd (4.92 mg/kg), Cu (3.45 mg/kg), and Pb (0.67 mg/kg) were detected in oyster samples collected during the summer, while Hg concentrations were similar (0.03 to 0.04 mg/kg) throughout all seasons. Results indicate that except for Cd, Crassostrea corteziensis accumulates metals to levels below those recommended by the US. FDA and the Mexican government. For Cd, its concentration correlates more strongly with the temperature of the oyster's environment rather than to the oyster growth cycle. PMID- 20585754 TI - Postoperative evaluation of tibial footprint and tunnels characteristics after anatomic double-bundle anterior cruciate ligament reconstruction with anatomic aimers. AB - Following anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with hamstring tendon autografts, 38 consecutive patients were evaluated with high-speed three-dimensional computed tomography. Scans were performed within 3 days following surgery. The length and width of the reconstructed ACL footprint were measured on axial images. Then, 3D images were converted into 2D with radiologic density for measurement purposes. Tunnel orientation was measured on AP and lateral views. In the sagittal plane, the center of the anteromedial (AMB) and posterolateral bundle (PLB) tibial attachment positions was calculated as the ratio between the geometric insertion sites with respect to the sagittal diameter of the tibia. In addition, the length from the anterior tibial plateau to the retro-eminence ridge was measured; the relationship of this line with the centers of the AM and PL tunnels was then measured. The AP length of the reconstructed footprint was 17.1 mm +/- 1.9 mm and the width 7.3 mm +/- 1.2 m. The distance from retro-eminence ridge to center of AM tunnel was 18.8 mm +/- 2.8 mm, and the distance from RER to center of PL tunnel was 8.7 mm +/- 2.6 mm. The distance between tunnels center was 10.1 mm +/- 1.7 mm. There were no significant differences between the intra- and inter-observer measurements. The bone bridge thickness was 2.1 mm +/- 0.8 mm. In the sagittal plane, the centers of the tunnel apertures were located at 35.7% +/- 6.7% and 53.7% +/- 6.8% of the tibia diameter for the AMB and PLB, respectively. The surface areas of the tunnel apertures were 46.3 mm(2) +/- 4.4 mm(2) and 36.3 mm(2) +/- 4.0 mm(2) for the AM and PL tunnels, respectively. The total surface area occupied by both tunnels was 82.6 mm(2) +/- 7.0 mm(2). In the coronal plane, tunnel orientation showed the AM tunnel was more vertical than the PL tunnel with a 10 degrees divergence (14.8 degrees vs. 24.1 degrees ). In the sagittal plane, both tunnels were almost parallel (29.9 degrees and 25.4 degrees for the AM and PL tunnels, respectively). When using anatomic aimers, the morphometric parameters of the reconstructed tibial footprint in terms of length and distances to the surrounding bony landmarks were similar to the native ACL tibial footprint. However, the native footprint width was not restored, and the surface area of the two tunnel apertures was in the lower range of the published values for the native footprint area. PMID- 20585755 TI - Electrical stimulation compared with tolterodine for treatment of urge/urge incontinence amongst women--a randomized controlled trial. AB - INTRODUCTION AND HYPOTHESIS: Few randomized controlled trials have compared electrical stimulation treatment with drug therapy. Our hypothesis was that electrical stimulation treatment in women with urgency/urge incontinence would be more efficient compared to drug treatment. METHODS: Women >=18 years of age with urgency/urge incontinence were randomized to receive either ten electrical stimulation treatments vaginally and transanally over a period of 5-7 weeks or tolterodine 4 mg orally once daily. RESULTS: Sixty-one women completed the study. There was no significant difference between the two treatment groups in micturition rate from baseline to 6 months, mean difference, -0.40 (95% confidence interval (CI), -1.61 to 0.82), but a clearly significant difference within each group for electrical stimulation, -2.8 (95% CI, -3.7 to -1.9), and for tolterodine, -3.2 (95% CI, -4.1 to -2.4). CONCLUSIONS: Both treatments reduced the number of micturitions, but electrical stimulation was not found to be superior to tolterodine. PMID- 20585756 TI - Postoperative urinary retention following vaginal mesh procedures for the treatment of pelvic organ prolapse. AB - INTRODUCTION AND HYPOTHESIS: The objective of the study was to assess vaginal mesh procedures and patient characteristics that are associated with postoperative urinary retention (PUR) following pelvic reconstructive surgery. METHODS: The charts of 142 patients who underwent transvaginal reconstructive surgery with mesh were included in the analysis. Primary outcome was the incidence of PUR following surgery with mesh. Patients were grouped according to discharge from the hospital with or without a catheter based on a standardized voiding trial. RESULTS: Forty-eight patients (34%) developed PUR after surgery. Of those, 30 patients (62.5%) had a combined anterior and posterior repair (p = 0.033). Mean preoperative anterior stage prolapse for patients with PUR compared with no PUR was 2.31 vs. 1.80 (p = 0.002). There was a greater association of PUR among patients with concomitant retropubic slings compared with transobturator slings (OR = 3.6, 95% confidence interval = 1.3-9.8). CONCLUSIONS: A higher preoperative anterior stage prolapse, combined anterior and posterior compartment repairs, and retropubic sling procedures appear to be associated with PUR. PMID- 20585757 TI - Prospective randomized trial comparing synthetic vs biological out-in transobturator tape: a mean 3-year follow-up study. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to prospectively and randomly compare the outcome of surgical treatment of female stress urinary incontinence (SUI) using the same outside-inside transobturator technique with biological (PelviLaceTO) or synthetic (UretexTO) material sling, evaluating if the biological material can prevent vaginal erosion retaining the "cure rate" of this surgical technique. METHODS: Seventy patients with SUI were selected, randomly assigned to either UretexTO (n = 34) or PelviLaceTO (n = 36), and underwent the same surgery. RESULTS: There is no significant difference between two study arms with regard to objective and subjective cure rates and quality of life. In both groups we had an overlap cure rate (UretexTO group 88.2% vs PelviLaceTO group 88.8%) at mean 3 years follow-up. It found no perioperative complications nor vaginal erosions. CONCLUSIONS: UretexTO and PelviLaceTO are two similarly safe and efficient slings in the management of SUI, with a good patient satisfaction and without any complications. PMID- 20585758 TI - Study of the sensitising potential of various textile dyes using a biphasic murine local lymph node assay. AB - Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of approximately 2 cm(2) on their backs and treated using a "sensitisation-challenge protocol". The shaved surface was treated once daily on days 1-3 with 50 microl of the test solution. Animals remained untreated on days 4-14. On days 15-17, mice were treated with 25 microl of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO(2) anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight, lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+ cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results, the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order (in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation potential of tested textile dyes and provides data allowing to discriminate them according to their potency. PMID- 20585759 TI - Impact of metabotropic glutamate 2/3 receptor stimulation on activated dopamine release and locomotion. AB - RATIONALE: Activation of metabotropic glutamate (mGlu) 2/3 receptors may provide a novel strategy for treating schizophrenia. This effect is thought to be mediated through dopamine-independent mechanisms because mGlu2/3-receptor agonists have no considerable affinity for dopamine receptors. These agonists, however, reduce amphetamine-induced hyperlocomotion suggesting that they influence dopamine neurotransmission. OBJECTIVE: We evaluated whether the inhibitory effect of mGlu2/3-receptor activation on amphetamine-induced hyperlocomotion correlates with attenuated dopamine release. We also assessed whether mGlu 2/3 receptor activation has inhibitory effects on activity-dependent vesicular release of dopamine in behaving animals. METHODS: Microdialysis was used to measure extracellular levels of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) of freely moving rats. The effect of the mGlu2/3 receptor agonist LY354740 on dopamine release and locomotion elicited by amphetamine, electrical stimulation of the ventral tegmental area, or L-dopa was assessed. RESULTS: We find that the inhibitory effect of mGlu2/3 activation on amphetamine-induced hyperlocomotion correlates with an attenuated increase in dopamine release in the NAc and DStr. However, when dopamine levels were increased by electrical stimulation of dopamine neurons or by administration of the dopamine precursor L-dopa, activation of mGlu2/3 receptors had no effect on dopamine release or on behavior. CONCLUSIONS: Activation of mGlu2/3 receptors attenuates amphetamine-induced dopamine release through a mechanism that does not affect activity dependent vesicular release, reuptake or synthesis of dopamine. PMID- 20585760 TI - Central serotonin transporter levels are associated with stress hormone response and anxiety. AB - RATIONALE: Negative mood states are characterized by both stress hormone dysregulation and serotonergic dysfunction, reflected by altered thalamic serotonin transporter (5-HTT) levels. However, so far, no study examined the individual association between cortisol response and cerebral in vivo 5-HTT levels in patients suffering from negative mood states. OBJECTIVE: The objective of this cross-sectional study was to assess the interrelation of cortisol response, thalamic 5-HTT levels, and anxiety in healthy subjects and two previously published samples of patients with unipolar major depression (UMD) and obsessive-compulsive disorder (OCD), controlling for age, gender, 5-HTT genotype, smoking, and seasonality. METHODS: Regional 5-HTT levels and cortisol response to dexamethasone-corticotropin (Dex-CRH) challenge were assessed in consecutive samples of medication-free patients suffering from UMD (N = 10) and OCD (N = 10), and 20 healthy volunteers. The intervention used was combined Dex-CRH test and [(11)C]DASB positron emission tomography. The main outcome measures were: 5-HTT binding potential (BP(ND)) in a predefined thalamic ROI, cortisol response defined as the maximum cortisol increase in the combined Dex-CRH-test, and state of anxiety from the state-trait-anxiety inventory. RESULTS: Reduced thalamic 5 HTT BP(ND) was associated with increased cortisol response (r = -0.35, p < 0.05; in patients: r = -0.53, p < 0.01) and with increased state anxiety (r = -0.46, p < 0.01), surviving correction for age, gender, 5-HTT genotype, smoking, and seasonality (p < 0.05). The 5-HTT genotype, on the contrary, was not significantly associated with cortisol response (p = 0.19) or negative mood (p = 0.23). CONCLUSION: The association between stress hormone response, thalamic 5 HTT levels, and anxiety in patients suffering from negative mood states suggests an interaction between two major mechanisms implicated in negative mood states in humans. PMID- 20585761 TI - Nicotine and food deprivation decrease the ability to resist smoking. AB - RATIONALE: Attempts to simultaneously control food intake and smoking may lead to smoking cessation failure. We sought to model this relationship using a human laboratory paradigm of smoking lapse behavior. OBJECTIVES: We examined the combined effect of food and nicotine deprivation, compared to nicotine deprivation alone, on the ability to resist smoking and on subsequent ad libitum smoking. METHODS: In a between-subjects design, daily smokers (N = 30) were all deprived of nicotine for 18 h and were either food-deprived (12 h) or not during a laboratory session. Following exposure to individualized food cues, participants had the option of initiating tobacco self-administration or delaying up to 50 min in exchange for monetary reinforcement. Subsequently, the tobacco self-administration period consisted of 1 h in which participants could choose to smoke or receive monetary reinforcement for cigarettes not smoked. RESULTS: Smokers who had been deprived of food and nicotine smoked their first cigarette sooner and were more likely to smoke at some point during the laboratory session, compared to those who were only nicotine-deprived. Those who were food- and nicotine-deprived smoked slightly more cigarettes than those who were nicotine deprived only, although this difference was not statistically significant. There were no sex differences in outcomes. Hunger and food craving ratings while trying to resist smoking were greater in the food + nicotine-deprived group. Tobacco craving was predictive of outcome in both conditions. CONCLUSIONS: These findings support the hypothesis that food deprivation can undermine a smoker's ability to resist smoking. PMID- 20585762 TI - Attention and reach-to-grasp movements in Parkinson's disease. AB - The role of attention in grasping movements directed at common objects has not been examined in Parkinson's disease (PD), though these movements are critical to activities of daily living. Our primary objective was to determine whether patients with PD demonstrate automaticity in grasping movements directed toward common objects. Automaticity is assumed when tasks can be performed with little or no interference from concurrent tasks. Grasping performance in three patient groups (newly diagnosed, moderate, and advanced/surgically treated PD) on and off of their medication or deep brain stimulation was compared to performance in an age-matched control group. Automaticity was demonstrated by the absence of a decrement in grasping performance when attention was consumed by a concurrent spatial-visualization task. Only the control group and newly diagnosed PD group demonstrated automaticity in their grasping movements. The moderate and advanced PD groups did not demonstrate automaticity. Furthermore, the well-known effects of pharmacotherapy and surgical intervention on movement speed and muscle activation patterns did not appear to reduce the impact of attention-demanding tasks on grasping movements in those with moderate to advanced PD. By the moderate stage of PD, grasping is an attention-demanding process; this change is not ameliorated by dopaminergic or surgical treatments. These findings have important implications for activities of daily living, as devoting attention to the simplest of daily tasks would interfere with complex activities and potentially exacerbate fatigue. PMID- 20585763 TI - Clinical safety of magnetic resonance imaging in patients with implanted SynchroMed EL infusion pumps. AB - INTRODUCTION: Patients with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential "for a delay in the return of proper drug infusion" and "for a delay in the logging of motor stall events," "a patient's pump must be interrogated after MRI exposure in order to confirm proper pump functionality." This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper pump infusion could lead to life-threatening baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps. METHODS: We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004. RESULTS: No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients. CONCLUSIONS: Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging. PMID- 20585764 TI - Presence of a central vein within white matter lesions on susceptibility weighted imaging: a specific finding for multiple sclerosis? AB - INTRODUCTION: Susceptibility weighted imaging depicts the perivenous extent of multiple sclerosis white matter lesions (MS-WML) in vivo by directly visualizing their centrally running vein. The aim of this study was to investigate the specificity of this finding for MS. METHODS: Fifteen patients with MS and 15 patients with microangiopathic white matter lesions (mWML) underwent 3T MRI, including a fluid-attenuated inversion recovery sequence (FLAIR) and a susceptibility weighted angiography (SWAN). All WMLs were identified on FLAIR and assigned to one of the following localizations: supratentorial peripheral, supratentorial periventricular, or infratentorial. Subsequently, the presence of a central vein within these lesions was assessed on SWAN. RESULTS: A total of 711 MS-WMLs and 1,119 m-WMLs were identified on FLAIR, all of which could also be visualized on SWAN. A central vein was detectable in 80% of the MS-WMLs and in 78% of the m-WMLs (in 73% and 76% of the peripheral, in 92% and 94% of the periventricular, and in 71% and 75% of the infratentorial MS-WMLs and m-WMLs, respectively). With regard to the supratentorial peripheral lesions, significantly more m-WMLs showed a central vein compared to the MS-WMLs. For the other localizations, there was no significant difference between the groups with regard to the percentage of lesions with central vein. CONCLUSIONS: Our results indicate that the detection of a central vein within a WML should not be considered a specific finding for MS; it is also found in WMLs of other etiologies. PMID- 20585765 TI - Thalamus lesions in chronic and acute seizure disorders. AB - INTRODUCTION: Transient signal changes in the pulvinar have been described following status epilepticus. However, we observed persistent thalamus changes after seizures. The purpose of this study was to characterize thalamus changes in patients with seizure disorders and to correlate imaging findings with clinical features. METHODS: We searched among 5,500 magnetic resonance imaging (MRI) exams performed in patients with seizures and identified 43 patients. The MRI scans of these patients were reviewed and correlated with clinical data. RESULTS: We identified four patterns of thalamus lesions: (a) fluid attenuated inversion recovery-hyperintense pulvinar lesions (20 patients), as known from status epilepticus. Ten patients in this group had a status epilepticus. Among the remaining patients, three had frequent seizures and seven had sporadic seizures. Twelve patients had follow-up exams for a median of 11 months. The lesions had persisted in 11/12 cases in the last available exam and were reversible in one case only. In seven cases, cone-shaped thalamus atrophy resulted, (b) linear defects in the medial and anterior thalamus (five patients), accompanied by atrophy of the mamillary body and the fornix in patients with chronic epilepsy, (c) extensive bilateral thalamus lesions in two patients with a syndrome caused by mutation in the mitochondrial polymerase gamma, and (d) other thalamus lesions not associated with the seizure disorder (16 patients). CONCLUSION: The spectrum of thalamus lesions in patients with seizure disorders is wider than previously reported. Postictal pulvinar lesions can persist and may result in thalamic atrophy. Linear defects in the anterior thalamus are associated with limbic system atrophy. PMID- 20585767 TI - Evaluation of small ischemic lesions after carotid artery stenting: the usefulness of thin-slice diffusion-weighted MR imaging. AB - INTRODUCTION: There has been concern regarding the usefulness of diffusion weighted imaging (DWI) to evaluate the ischemic lesions associated with carotid artery stent placement (CAS). Some small lesions may be detected not by standard DWI but by thin-slice DWI alone, since most of the cerebral lesions are very small in size and clinically silent. The purpose of this study is to compare the detectability of the small ischemic lesions after CAS by standard and thin-slice DWI. METHODS: Both standard DWI with slice thickness of 6 mm and thin-slice DWI with slice thickness of 2 mm were obtained at the same MR examination within 2 to 7 days after 20 procedures of CAS in 17 patients. Number and measured diameter size of the detected lesions on both DWI were compared. RESULTS: All CAS procedures in 17 patients were successfully completed. The focal ischemic lesions were detected in 14 of 20 on thin-slice DWI and seven examinations on standard DWI. The total numbers of hyperintense lesions were 31 on thin-slice DWI and ten on standard DWI (p < 0.001). The sizes of these ten lesions on thin-slice DWI were larger than those of standard DWI, and the mean size of the thin-slice DWI and that of standard DWI were significantly different (p < 0.005). CONCLUSION: Thin-slice DWI was able to detect small cortical lesions better than standard DWI. Thin-slice DWI may be useful to evaluate small silent ischemic lesions after CAS. PMID- 20585769 TI - Biliary cystadenoma with bile duct communication depicted on liver-specific contrast agent-enhanced MRI in a child. AB - Biliary cystadenoma is a benign, but potentially malignant, cystic neoplasm of the biliary ducts occurring most commonly in middle-aged females and very rarely in children. We present a 9-year-old boy with biliary cystadenoma, diagnosed by MRI using a new liver-specific contrast agent (gadoxetic acid) that is eliminated by the biliary system. The images clearly demonstrate the communication between the multiloculated cystic mass and the biliary tree, suggesting the possibility of biliary cystadenoma. Due to the malignant potential of a cystadenoma, the lesion was resected. The resection was complete and the postoperative course was uneventful. PMID- 20585768 TI - CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations. AB - Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2 weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. PMID- 20585770 TI - Thirty allele-level haplotypes centered around KIR2DL5 define the diversity in an African American population. AB - KIR2DL5 alleles were physically linked to alleles at adjacent KIR loci to define this region of KIR haplotypes in 55 gene-positive random African Americans. The majority carried KIR2DL5B. Three KIR2DL5A and six KIR2DL5B alleles that have been previously described and 11 novel KIR2DL5 alleles were identified by DNA sequencing. Novel alleles included variation that may impact promoter activity; two alleles carried nonsynonymous coding region variation. Based on linkage with KIR2DS1, KIR2DS3, KIR2DS5, KIR2DL2, KIR2DL3, and KIR3DS1 alleles, seven haplotypes of KIR2DL5A and 23 haplotypes of KIR2DL5B were observed. The phylogenetic relationships among the KIR2DL5 alleles predicted their association with either KIR2DS3 (six alleles) or KIR2DS5 (seven alleles). All of the KIR2DL5A alleles were linked either to KIR3DS1*01301 or KIR3DS1*049N. The majority of the KIR2DL5B alleles were linked to seven KIR2DL2 alleles; two were linked to a novel allele of KIR2DL3. These findings underscore the diversity of KIR haplotypes present in this population. PMID- 20585771 TI - Engineering of glycerol dehydrogenase for improved activity towards 1, 3 butanediol. AB - The objective of this study was to use protein engineering techniques to enhance the catalytic activity of glycerol dehydrogenase (GlyDH) on racemic 1, 3 butanediol (1, 3-BDO) for the bioproduction of the important pharmaceutical intermediate 4-hydroxy-2-butanone. Three GlyDH genes (gldA) from Escherichia coli K-12, Salmonella enterica, and Klebsiella pneumoniae MGH78578 were shuffled to generate a random mutagenesis library. The nitroblue tetrazolium/phenazine methosulfate high throughput screening protocol was used to select four chimeric enzymes with up to a 2.6-fold improved activity towards 1, 3-BDO. A rational design method was also employed to further improve the enzyme activity after DNA shuffling. Based on the homology model of GlyDH (Escherichia coli), Asp121 was predicted to influence 1, 3-BDO binding and replaced with Ala by site-directed mutagenesis. Combination of the mutations from both DNA shuffling and rational design produced the best mutant with a V (max) value of 126.6 U/mg, a 26-fold activity increase compared with that of the wild type GlyDH from E. coli. PMID- 20585772 TI - Engineering of glycosylation in yeast and other fungi: current state and perspectives. AB - With the increasing demand for recombinant proteins and glycoproteins, research on hosts for producing these proteins is focusing increasingly on more cost effective expression systems. Yeasts and other fungi are promising alternatives because they provide easy and cheap systems that can perform eukaryotic post translational modifications. Unfortunately, yeasts and other fungi modify their glycoproteins with heterogeneous high-mannose glycan structures, which is often detrimental to a therapeutic protein's pharmacokinetic behavior and can reduce the efficiency of downstream processing. This problem can be solved by engineering the glycosylation pathways to produce homogeneous and, if so desired, human-like glycan structures. In this review, we provide an overview of the most significant recently reported approaches for engineering the glycosylation pathways in yeasts and fungi. PMID- 20585773 TI - Comparison of diagnostic performances of three different software packages in detecting coronary artery disease. AB - PURPOSE: Quantification of myocardial perfusion scintigraphy is frequently performed to assist physicians in detecting coronary artery disease (CAD). Software packages provide automated quantification of perfusion data. We aimed to compare the three commonly used software packages, Emory Cardiac Toolbox (ECT v2 and ECT v3), 4D-MSPECT (4DM v2 and 4DM v4) and Quantitative Perfusion SPECT (QPS v3 and QPS v4). METHODS: We selected 283 patients who had a myocardial perfusion scintigraphy with (201)Tl followed by coronary angiography within 3 months. Summed stress score (SSS), summed difference score (SDS), total stress defect extent (TDE) and regional stress defect extent values were obtained from programs. A >=70% stenosis in coronary arteries and their major branches was considered positive for CAD. A subgroup of patients was used to form an institutional normal database for QPS and 4DM. Receiver-operating characteristic (ROC) analysis to detect CAD was performed. RESULTS: Mean SSS +/- SD (vendor) for ECT v3, QPS v4 and 4DM v4 were 9.2 +/- 7.1, 10.1 +/- 6.8 and 5.5 +/- 6.1, respectively. Area under the curve (AUC) values of SSS ROC analysis were 0.738 +/ 0.031 for QPS v3, 0.755 +/- 0.030 for QPS v4, 0.758 +/- 0.030 for ECT v2, 0.778 +/- 0.029 for ECT v3 and 0.771 +/- 0.030 for 4DM v4. The AUC values for TDE were 0.755 +/- 0.030 for QPS v4, 0.769 +/- 0.030 for ECT v3 and 0.775 +/- 0.029 for 4DM v4. The differences were not significant for both SSS and TDE. Differences of AUC between regional stress defect extent values of programs and AUC of SSS between institutional and vendor normal databases were not significant. CONCLUSION: The diagnostic performances of programs to detect CAD are similar. However, there are differences in the magnitudes of the quantitative values produced by the programs. PMID- 20585774 TI - Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma. AB - PURPOSE: The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2 nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies. METHODS: (18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0 degrees then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC). RESULTS: EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (~3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ~13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other (18)F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of (18)F-EF5 was confirmed by IHC. CONCLUSION: These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements. PMID- 20585775 TI - A fast cardiac gamma camera with dynamic SPECT capabilities: design, system validation and future potential. AB - PURPOSE: The goal of this study is to present the Discovery NM 530c (DNM), a cardiac SPECT camera, interfacing multi-pinhole collimators with solid-state modules, aiming at slashing acquisition time without jeopardizing quality. DNM resembles PET since it enables 3-D SPECT without detector motion. We further envision how these novel capabilities may help with current and future challenges of cardiac imaging. METHODS: DNM sensitivity, spatial resolution (SR) and energy resolution (ER), count rate response, cardiac uniformity and cardiac defect contrast were measured and compared to a dedicated cardiac, dual-head standard SPECT (S-SPECT) camera. RESULTS: DNM sensitivity was more than threefold higher while SR was notably better. Significantly, SR was the same for (99m)Tc and (201)Tl. ER was improved on DNM and allowed good separation of (99m)Tc and (123)I spectral peaks. Count rate remained linear on DNM up to 612 kcps, while S-SPECT showed severe dead time limitations. Phantom studies revealed comparable uniformity and defect contrast, notwithstanding significantly shorter acquisition time for the DNM. First patient images, including dynamic SPECT, are also presented. CONCLUSION: DNM is raising the bar for expedition and upgrade of practice. It features high sensitivity as well as improved SR, temporal resolution and ER. It enables reduction of acquisition time and fast protocols. Importantly, it is potentially capable of dynamic 3-D acquisition. The new technology is potentially upgradeable and may become a milestone in the evolution of nuclear cardiology as it assumes its key role in molecular imaging of the heart. PMID- 20585777 TI - Direct 64-row MDCT venography in the diagnosis of an inferior vena cava leiomyosarcoma. AB - We report the usefulness of a technique called direct-MDCT venography in the diagnostic workup of a patient with an inferior vena cava leiomyosarcoma. The technique consists in the injection of contrast agent through both lower limbs achieving maximum enhancement in the inferior vena cava. Images are similar to those of the gold standard conventional cavography. To our knowledge, this is the first description of the direct-MDCT imaging appearance of an inferior vena cava leiomyosarcoma. PMID- 20585776 TI - Biodistribution and radiation dosimetry of a positron emission tomographic ligand, 18F-SP203, to image metabotropic glutamate subtype 5 receptors in humans. AB - PURPOSE: A new PET ligand, 3-fluoro-5-(2-(2-(18)F-(fluoromethyl)-thiazol-4 yl)ethynyl)benzonitrile ((18)F-SP203), is a positron emission tomographic radioligand selective for metabotropic glutamate subtype 5 receptors. The purposes of this study were to estimate the radiation-absorbed doses of (18)F SP203 in humans and to determine from the distribution of radioactivity in bone structures with various proportions of bone and red marrow whether (18)F-SP203 undergoes defluorination. METHODS: Whole-body images were acquired for 5 h after injecting (18)F-SP203 in seven healthy humans. Urine was collected at various time points. Radiation-absorbed doses were estimated by the Medical Internal Radiation Dose scheme. RESULTS: After injecting (18)F-SP203, the two organs with highest radiation exposure were urinary bladder wall and gallbladder wall, consistent with both urinary and fecal excretion. In the skeleton, most of the radioactivity was in bone structures that contain red marrow and not in those without red marrow. Although the dose to red marrow (30.9 microSv/MBq) was unusually high, the effective dose (17.8 microSv/MBq) of (18)F-SP203 was typical of that of other (18)F radiotracers. CONCLUSION: (18)F-SP203 causes an effective dose in humans typical of several other (18)F radioligands and undergoes little defluorination. PMID- 20585779 TI - CT-guided percutaneous drainage of infected collections due to gastric leak after sleeve gastrectomy for morbid obesity: initial experience. AB - This study was designed to evaluate the efficacy and safety of computed tomography (CT)-guided drainage in treating infected collections due to gastric leak after laparoscopic sleeve gastrectomy for morbid obesity. From January 2007 to June 2009, 21 patients (9 men and 12 women; mean age, 39.2 (range, 26-52) years) with infected collections due to gastric leak after laparoscopic sleeve gastrectomy for morbid obesity underwent image-guided percutaneous drainage. All procedures were performed using CT guidance and 8- to 12-Fr pigtail drainage catheters. Immediate technical success was achieved in all 21 infected collections. In 18 of 21 collections, we obtained progressive shrinkage of the collection with consequent clinical success (success rate 86%). In three cases, the abdominal fluid collection was not resolved, and the patients were reoperated. Among the 18 patients who avoided surgery, 2 needed replacement of the catheter due to obstruction. No major complications occurred during the procedure. The results of our study support that CT-guided percutaneous drainage is an effective and safe method to treat infected abdominal fluid collections due to gastric leak in patients who had previously underwent laparoscopic sleeve gastrectomy for morbid obesity. It may be considered both as a preparatory step for surgery and a valuable alternative to open surgery. Failure of the procedure does not, however, preclude a subsequent surgical operation. PMID- 20585778 TI - Determination of lowest instrumented vertebra by the location of apical vertebra in Lenke type 1 adolescent idiopathic scoliosis. AB - We postulated that the lowest instrumented vertebra (LIV) can be determined based on the apical vertebra. Seventy-two Lenke type 1 patients (average age: 13.6 years) receiving posterior spinal fusion were randomised into two groups. In group A, the apical vertebra was used to determine the LIV and in group B the neutral vertebra was used. All patients had Cobb angles <90 degrees and average follow-up was over three years. Posteroanterior and lateral standing radiographs were used to assess flexibility, Cobb angle and distance from the C7 line to the central sacral vertical line. Both methods produced statistically significant changes in Cobb angle, sagittal T5-T12 and plumb line deviation, and there were no significant differences between the two methods. More cases of imbalance occurred in group B (five) than group A (two). We conclude that the apical vertebra can be used to determine the LIV in patients with Lenke type 1 adolescent idiopathic scoliosis. PMID- 20585780 TI - Endovascular revascularization of chronically thrombosed arteriovenous fistulas and grafts for hemodialysis: a retrospective study in 15 patients with 18 access sites. AB - The current study retrospectively evaluated whether endovascular revascularization of chronically thrombosed and long-discarded vascular access sites for hemodialysis was feasible. Technical and clinical success rates, postintervention primary and secondary patency rates, and complications were reported. During a 1-year period, we reviewed a total of 924 interventions performed for dysfunction and/or failed hemodialysis vascular access sites and permanent catheters in 881 patients. In patients whose vascular access-site problems were considered untreatable or were considered treatable with a high risk of failure and access-site abandonment, we attempted to revascularize (resurrect) the chronically occluded and long-discarded (mummy) vascular access sites. We attempted to resurrect a total of 18 mummy access sites (mean age 46.6 +/- 38.7 months; range 5-144) in 15 patients (8 women and 7 men; mean age 66.2 +/ 11.5 years; age range 50-85) and had an overall technical success rate of 77.8%. Resurrection failure occurred in 3 fistulas and in 1 straight graft. The clinical success rate was 100% at 2 months after resurrection. In the 14 resurrected vascular access sites, 6 balloon-assisted maturation procedures were required in 5 fistulas; after access-site maturation, a total of 22 interventions were performed to maintain access-site patency. The mean go-through time for successful resurrection procedures was 146.6 +/- 34.3 min (range 74-193). Postmaturation primary patency rates were 71.4 +/- 12.1% at 30 days, 57.1 +/- 13.2% at 60 days, 28.6 +/- 13.4% at 90 days, and 19 +/- 11.8% at 180 days. Postmaturation secondary patency rates were 100% at 30, 60, and 90 days and 81.8 +/- 11.6% at 180 days. There were 2 major complications consisting of massive venous ruptures in 2 mummy access sites during balloon dilation; in both cases, prolonged balloon inflation failed to achieve hemostasis, but percutaneous N butyl cyanoacrylate glue seal-off was performed successfully. Percutaneous resurrection of mummy vascular access sites for hemodialysis is technically feasible with high clinical success rates. In selected patients, resurrection of mummy access sites provides long-discarded access sites one more chance to be used for hemodialysis in an effort to preserve potential extremity sites for future access-site placement and to prevent long-term catheter indwelling. PMID- 20585781 TI - Dynamic computed tomography angiography: role in the evaluation of popliteal artery entrapment syndrome. AB - This study reviews our experience with dynamic computed tomographic angiography (CTA) as an imaging modality in the evaluation of popliteal artery entrapment syndrome (PAES). Eight patients with surgically proven PAES were included in this study. Dynamic CTA studies performed with the feet in neutral and plantar flexed positions were reviewed for the detailed anatomy of the region and to define the location and extent of the stenosis, occlusions and collateral circulation. These findings were compared with intraoperative observations. CTA provided adequate angiographic and anatomic information required to arrive at the diagnosis and make a surgical decision. Thirteen limbs were affected in eight patients. There was popliteal artery occlusion in four limbs, stenosis at rest that was accentuated on stress imaging in two limbs, and patent popliteal artery with marked stenosis on stress imaging in seven limbs. Long-segment stenosis was seen in functional entrapment compared to short-segment stenosis in anatomic PAES. Anteroposterior compression of the popliteal artery in anatomic PAES unlike the side-to-side compression in functional PAES was a unique observation in this study. The CTA and surgical characterisation and classification of PAES matched in all the patients, except for misinterpretation of compressing fibrous bands as accessory slips of muscles in three limbs. In conclusion, dynamic CTA is a robust diagnostic tool that provides clinically relevant information and serves as a rapidly performed and easily available "one-stop-shop" imaging modality in the management of PAES. PMID- 20585782 TI - Frequency, anatomical properties and innervation of axillary arch and its relation to the brachial plexus in human fetuses. AB - PURPOSE: "Axillary Arch" (AA) is the main musculotendinous variation of the axillary region. The aim of this study was to reveal the frequency, anatomical properties, and innervation of AA and its relation with brachial plexus in human fetuses. METHODS: In this study, 50 human fetuses (male: 20, female: 30), gestation age varied between 16 and 38 weeks (mean +/- SD: 23.3 +/- 5.3 week), were dissected at the anatomy laboratory of Mersin University, Faculty of Medicine. RESULTS: AA was found in 11 of the 50 fetuses, and in 3 of 11, it was bilateral. Among both sides, 6 of 14 AAs were on the right and 8 were on the left side. Seven of AA's (7% of the specimens) were in muscular and 7 (7%) of them were in musculotendinous structure. With regard to Testut's classification, six (6%) of them were of complete type, six (6%) were incomplete and two (2%) were concordant with both types. Three different types of AA were defined considering the shapes of the arches. According to our classification, seven of the AAs were of type 1, two of them were of type 2 and five of them were of type 3. Additionally, the incidence of the T2 spinal nerve joining the brachial plexus was significantly higher in the specimens with AA (p = 0.001). CONCLUSIONS: Each type of AA described in this study is thought to have individual clinical significance. Being aware of AA and its types can be important to determine a safe approach to the axillary region for surgeons. In addition, our results show the relation between the occurrence of AA and the variations in the formation of the proximal part of brachial plexus. PMID- 20585783 TI - How safe is the use of ultrasound-guided cutting needle biopsy in the head and neck? AB - OBJECTIVES: To analyse the risks and potential complications of cutting needle biopsy (CNB) for head and neck lesions, which have not been fully discussed previously. MATERIALS AND METHODS: We performed a systematic clinicopathological quality assessment study of 200 patients with cervicofacial lesions who underwent 444 CNB procedures with a semiautomatic biopsy gun. RESULTS: Adequate target tissue was obtained in 181 patients and revealed malignancy in 127 patients (70.2%). Follow-up uncovered 2 (1.1%) false-negative results. Emphasis was placed on the analysis of 4 minor and 2 major complications that were recorded. One patient suffered from a cerebrovascular event and died after dissection of a distinctively kinked carotid artery. The risks of CNB are discussed and compared to fine-needle aspiration cytology (FNAC) and open biopsy and related to series of parameters. CONCLUSION: CNB is a safe and reliable technique in the majority of cases but its risks in the head and neck are not negligible due to the proximity of major neurovascular structures and airways. We recommend special attention after neck surgery and radiotherapy and when the target is not clearly circumscribed and is close to major vessels. PMID- 20585784 TI - MRI for the evaluation of gastric physiology. AB - BACKGROUND: Evaluation of gastric physiology (gastric emptying and motility) is important for the diagnosis of disturbances such as functional dyspepsia. MRI is a non-invasive technique that allows simultaneous registration of gastric emptying and motility. AIM: To provide an overview of the literature of studies that used MRI as a tool for evaluation of gastric function in both research and clinical settings. MATERIALS AND METHODS: A MEDLINE search was performed (1990 2008) directed at the radiology and gastroenterology literature on gastric physiology. Key words that were used included: functional tests, gastric emptying, gastric motility, gastric physiology and MRI. Twenty-five articles fulfilled the inclusion criteria and were included in the analysis. RESULTS AND CONCLUSION: Over the last decade, MRI has developed as a reliable, non-invasive method for detailed evaluation of gastric emptying and motility without the disadvantages of ionizing radiation and without the use of intragastric catheters that influence gastric physiology. PMID- 20585785 TI - High-pitch dual-source CT coronary angiography: systolic data acquisition at high heart rates. AB - OBJECTIVE: To assess the effect of systolic data acquisition for electrocardiography (ECG)-triggered high-pitch computed tomography (CT) on motion artefacts of coronary arteries in patients with high heart rates (HRs). METHODS: Eighty consecutive patients (15 women, age 67 +/- 14 years) with HR >= 70 bpm underwent CT angiography of the thoracic aorta (CTA) on 128-slice dual-source CT in ECG-triggered high-pitch acquisition mode (pitch = 3.2) set at 60% (group A, n = 40) or 30% (group B, n = 40) of the RR interval. Two blinded readers graded coronary artery image quality on a three-point scale. Radiation doses were calculated. RESULTS: Inter-observer agreement in grading image quality of the 1,154 coronary segments was good (kappa = 0.62). HRs were similar in groups A and B (85 +/- 13 bpm vs 85 +/- 14 bpm, p not significant). Significantly fewer coronary segments with non-diagnostic image quality occurred (i.e. score 3) in group B than in group A [2.8% (16/579) vs 8.3% (48/575), p < 0.001]. Seventeen patients (42.5%) of group A and 12 patients (30.0%) of group B had at least one non-diagnostic segment. Effective radiation doses were 2.3 +/- 0.3 mSv for chest CTA. CONCLUSION: A systolic acquisition window for high-pitch dual-source CTA in patients with high HRs (>= 70 bpm) significantly improves coronary artery image quality at a low radiation dose. PMID- 20585786 TI - Social behavior and pheromonal communication in reptiles. AB - The role of pheromones in orchestrating social behaviors in reptiles is reviewed. Although all reptile orders are examined, the vast majority of the literature has dealt only with squamates, primarily snakes and lizards. The literature is surprisingly large, but most studies have explored relatively few behaviors. The evolution of chemical signaling in reptiles is discussed along with behaviors governed by pheromones including conspecific trailing, male-male agonistic interactions, sex recognition and sex pheromones, and reptilian predator recognition. Nonreptilian prey recognition by chemical cues was not reviewed. The recent literature has focused on two model systems where extensive chemical ecology studies have been conducted: the reproductive ecology of garter snakes and the behavioral ecology of Iberian lacertid lizards. In these two systems, enough is known about the chemical constituents that mediate behaviors to explore the evolution of chemical signaling mechanisms that affect life history patterns. In addition, these models illuminate natural and sexual selection processes which have lead to complex chemical signals whose different components and concentrations provide essential information about individuals to conspecifics. Reptiles provide excellent candidates for further studies in this regard not only in squamates, but also in the orders where little experimental work has been conducted to date. PMID- 20585787 TI - MGMT gene promoter methylation in pediatric glioblastomas. AB - PURPOSE: Relatively few studies have been performed on molecular properties of pediatric glioblastoma multiforme (GBM). Methylation of DNA repair gene O(6) methylguanine-DNA methyltransferase (MGMT) promoter region has been associated with favorable prognosis and prolonged survival in adult GBM patients treated with temozolomide (TMZ). We explored the frequency of MGMT gene promoter methylation in pediatric glioblastomas and compared it with the known molecular alterations in p53. METHODS: Twenty pediatric GBM cases were selected. MGMT promoter methylation was assessed by methylation specific PCR. p53 expression was determined by immunohistochemistry. RESULTS: MGMT gene promoter methylation was observed in 50% of pediatric glioblastomas. p53 protein expression was detected in 60% of cases. Seventy percent of cases with methylated MGMT promoter were p53 immunopositive. CONCLUSIONS: The frequency of MGMT gene promoter methylation in pediatric GBMs was similar to adult GBM patients. The pediatric GBMs should also be investigated for MGMT promoter methylation to identify a subset of patients likely to benefit from TMZ therapy. p53 protein overexpression was more common in pediatric primary GBMs. To the best of our knowledge this is only the second study on MGMT gene promoter methylation status in pediatric GBMs. PMID- 20585789 TI - Evaluation of cardiac autonomic functions in patients with ankylosing spondylitis via heart rate recovery and heart rate variability. AB - OBJECTIVE: The aim of this study was to evaluate heart rate variability (HRV) and heart rate recovery (HRR) in otherwise healthy ankylosing spondylitis (AS) patients and control subjects. METHODS: A total of 28 patients with AS and 30 volunteers matched for age and sex were enrolled. All subjects underwent HRV analysis, exercise testing (ET), and transthoracic echocardiography. HRR indices were calculated by subtracting first, second, and third minute heart rates (HR) from the maximal HR. RESULTS: The AS and control groups were similar with respect to age (28.7 +/- 5.7 vs. 29.3 +/- 5.8 years), gender distribution [(male/female) 24/4 vs. 26/4], and left ventricular ejection fraction (LVEF) (63.8 +/- 2.8% vs. 65.7 +/- 3.6%). Mean HRR1 (24.8 +/- 4.2 vs. 28.8 +/- 5.5, P = 0.001) and HRR2 (42.0 +/- 4.4 vs. 48.0 +/- 6.3, P = 0.001) values were significantly higher in control group. SDNN, SDANN, RMSDD, and PNN50 significantly decreased; LF and LF/HF increased in AS patients compared with control subjects. CONCLUSIONS: Patients with AS has lower HRR and HRV indices with respect to normal subjects. Cardiac autonomic functions might be involved in AS patients even in patients without cardiac symptoms. PMID- 20585790 TI - Silicone ring versus pneumatic cuff tourniquet: a comparative quantitative study in healthy individuals. AB - INTRODUCTION: The aim of the present study was to compare a new silicone ring tourniquet (SRT) with a classic pneumatic cuff tourniquet (PT) in terms of tolerance and recovery time following their use in healthy volunteers. METHODS: Both tourniquets were applied in the arm and thigh of 15 healthy unmedicated volunteers. PT pressure was kept at 100 mmHg above the systolic blood pressure. The appropriate model of the SRT was used according to the systolic blood pressure. Pain was assessed by visual analogue scale and arterial blood pressure, pulse rate and oxygen saturation were monitored in all volunteers. RESULTS: There was no statistically significant difference in tolerance time between SRT and PT in the arm (19.13 vs. 18.25 min) and thigh (21.52 vs. 21.39 min) nor in recovery time between the two devices. CONCLUSION: The SRT performed similarly to the classic PT in terms of tolerance and recovery time when applied in the arm and thigh of unmedicated healthy volunteers. PMID- 20585791 TI - Anatomical considerations of the internal iliac artery in association with the ilioinguinal approach for anterior acetabular fracture fixation. AB - INTRODUCTION: Vascular injury may be encountered during an anterior approach to the pelvis or acetabulum-be it due to hematoma decompression, clot dislodgement during fracture manipulation, or iatrogenic. This can be associated with significant bleeding, hemodynamic instability, and subsequent morbidity. If the exact source of bleeding cannot be easily identified, compression of the internal iliac artery may be a lifesaving procedure. MATERIALS AND METHODS: We describe an extension of the lateral window of the ilioinguinal (or Olerud) approach elaborated on cadavers. RESULTS: The approach allows emergent access the internal iliac artery and intraoperative cross-clamping of the internal iliac vessels to control bleeding. CONCLUSION: The approach allows rapid access to the internal iliac artery. The surgeon should be familiar, however, with the surgical anatomy of this region to avoid potential injury to the ureter, peritoneum, lymphatics, and sympathetic nerves overlying the vessels when using the approach described. PMID- 20585792 TI - Osteoporosis prevalence and fracture characteristics in elderly female patients with fractures. AB - PURPOSE: The aim of this study was to characterize the features of fractures that occur in female patients with osteoporosis in the setting of a typical trauma hospital. METHODS: Observational study was conducted on 233 women aged 50 years and above reporting to a trauma center with a fracture. Fracture location, fracture classification and cause of fracture were obtained and compared with bone mineral status assessed by DXA at the spine. RESULTS: Our findings indicate that with increasing patient age, the majority of fractures occur after a minor traumatic event. In more than one-third of all fractures after minor trauma, the patients were diagnosed with osteoporosis. The overall prevalence of osteoporosis in patients older than 50 years with fractures was more than 30% and was increasing with age. Most strikingly, one-third of the patients have had a previous fracture at a location that should have triggered the assessment of bone health status, but only 25% of them had received any form of osteoporosis treatment. CONCLUSION: For patients older than 50 years reporting to a trauma unit with a fracture, osteoporosis has a considerable prevalence. The large number of patients who have had a previous fracture emphasizes the necessity for an effective implementation of treatment algorithms for elderly patients with osteoporosis in the setting of a trauma hospital. PMID- 20585793 TI - Acute postoperative infection with Aeromonas hydrophila after using medical leeches for treatment of venous congestion. AB - INTRODUCTION: Venous convulsion after reconstructive microsurgery procedures is one major complication a surgeon has to deal with. Today, especially in the field of reconstructive microsurgery, medicinal leech therapy enjoys a renaissance. The potential risks such as infections associated with leech therapy are generally underestimated and not sufficiently discussed in literature. METHOD/PATIENTS: We present five male patients with an average age of 47 years. All patients suffered from a trauma incident, which had to be treated as an emergency. Three patients showed, postoperatively, a venous congestion after the reconstructive procedures. Another two patients with flap reconstruction and flap training developed venous problems after 12 and 14 days. In all five cases, the indication was given to use medical leeches (Hirudo medicinalis). In all the patients, a local infection of the injured extremity could be regarded after beginning with the leech treatment. The treatment duration with medical leeches for postoperative venous congestion was an average of 6 days. RESULTS: The reconstructive procedures in all five cases were unfortunately unsuccessful as major local infections were observed. Microbiological analyses showed, in all cases, an infection with Aeromonas hydrophila. CONCLUSION: We recommend making a considered indication for leech therapy, to diagnose wound infections early and to think about prophylactic antibiotics in patients with leech application. PMID- 20585794 TI - Popliteal soft tissue tumor associated with hamstring injury. AB - We report herein a very rare case of semitendinosus tear that formed a tumor in the popliteal region after not having recovered as a result of only being instructed to rest. The soft tissue tumor was discovered on ultrasonography 4 months after pain and sensation of discomfort appeared in the popliteal region. We considered this symptom as dependent on the presence of the tumor and selected surgical treatment. Intraoperatively, this soft tissue tumor was connected with the pes anserinus by tendinous tissue. On pathological examination, the soft tissue tumor was diagnosed as skeletal muscle showing necrosis. From imaging, operative findings, and pathological diagnosis, this was considered to represent a rare case in which myorrhexis developed into a soft tissue tumor in the popliteal region after a semitendinosus tear remained unhealed and was neglected over the long term. Although we had trouble confirming a diagnosis and treatment procedure, we were able to acquire good results with surgical treatment. This is, to the best of our knowledge, the first report of damaged semitendinosus becoming a soft tissue tumor in the popliteal region after long-term neglect without healing. PMID- 20585795 TI - Replication dynamics at common fragile site FRA6E. AB - The replication dynamics at common fragile site FRA6E has been evaluated by molecular combing and interphase fluorescent in situ hybridisation (FISH) in primary human lymphocytes cultured under normal or aphidicolin-induced stress conditions. FRA6E is one of the most frequently expressed common fragile sites of the human genome. It harbours several genes, PARK2 being regarded as the most relevant one. According to the results obtained from interphase FISH analysis, FRA6E can be considered a mid-late-replicating sequence characterised by heterogeneous replication timing. Molecular combing did not reveal specific replication parameters at the fragile site: fork rates were highly comparable to those detected at an early replicating locus (LMNB2) used as control and in very good agreement with the whole-genome data obtained in parallel. The same indication applied to the density of initiation zones, the inter-origin distances from adjacent ongoing forks, the frequencies of unidirectional forks, fork arrest events and asynchronous forks. Interestingly, PARK2 appeared embedded in an early/late replication transition zone, corresponding to intron 8 (162 kb) and to the fragility core of FRA6E. In cells exposed to aphidicolin, few forks progressing at a rather slow rate were observed, the majority of them being unidirectional, but again a specific response of the fragile site was not observed. In summary, at FRA6E the replication process is not impaired per se, but chromosome breakages occur preferentially at an early/late replication transition zone. Aphidicolin might increase the occurrence of breakage events at FRA6E by prolonging the time interval separating the replication of early and late replication domains. These results may be of general significance to address the problem of fragile site instability. PMID- 20585796 TI - Assault-induced Takotsubo cardiomyopathy associated with persisting anterograde amnesia and myopathy. AB - Takotsubo cardiomyopathy is characterized by transient left ventricular dysfunction, electrocardiographic changes, and minimal release of myocardial enzymes that mimic acute myocardial infarction in patients without coronary artery disease. Takotsubo cardiomyopathy is frequently triggered by emotional or physical stress and occurs primarily in post-menopausal women. The pathomechanism of Takotsubo cardiomyopathy is, so far, unknown. Stress-induced amnesia is probably induced by perturbation of the hippocampal function. Assault-induced Takotsubo cardiomyopathy associated with amnesia has not been reported so far. In a 77-year-old Caucasian female, hospitalized because of confusion, anterograde amnesia, and hypertension after she had been assaulted by a female who sneaked up to her when she was unlocking the door of her apartment, Takotsubo cardiomyopathy was diagnosed based on clinical findings, electrocardiography, echocardiography, and coronary angiography. Follow-up after 8 weeks showed a regression of electrocardiographic and echocardiographic abnormalities; the amnesia for the assault, however, remained unchanged. This case shows that Takotsubo cardiomyopathy may be triggered by emotional stress induced during an assault. Assault-induced stress may not only induce Takotsubo cardiomyopathy but also amnesia for some of the events that occurred during the act. PMID- 20585797 TI - Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis. AB - BACKGROUND: To demonstrate the expression of lymphotactin and its receptor (XCR) in the iris/ciliary body and popliteal lymph node, and to clarify their roles in experimental autoimmune anterior uveitis (EAAU). METHODS: Uveitis was induced in Lewis rats by injection of melanin-associated antigen into the peritoneum and footpad. At defined time points, mRNA expression levels of lymphotactin and XCR in the iris/ciliary body and popliteal lymph node were measured by semiquantitative polymerase chain reaction. Lymphotactin levels in aqueous humor and serum after immunization were determined by enzyme-linked immunosorbent assay. In a separate experiment, an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), was injected daily into the intraperitoneum after immunization. Cellular sources of lymphotactin were determined by immunhistochemical staining and flow cytometry. RESULTS: Lymphotactin mRNA was upregulated in the iris/ciliary body with a peak level at day 14, which is in line with the disease course. XCR mRNA was expressed maximally and then declined gradually from days 5 to 21. With an expression pattern similar to that of mRNA expression, lymphotactin in aqueous humor had attracted corresponding numbers of leukocytes. PDTC markedly inhibited the expression of lymphotactin in aqueous humor and serum. Immunohistochemical staining and flow cytometry analysis revealed that the expression of lymphotactin was detected in infiltrated inflammatory cells, dominantly CD8+ T cells, and increased along with inflammation. CONCLUSIONS: The lymphotactin and XCR interaction might direct distinct lymphocytes subsets to inflammatory sites. Lymphotactin could regulate the inflammatory process. Lymphotactin expression may be modulated, at least in part, through the NF-kappaB signaling pathway. PMID- 20585798 TI - Rubella virus as a possible etiological agent of Fuchs heterochromic iridocyclitis. AB - BACKGROUND: To determine whether rubella virus is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). METHODS: Fourteen patients (14 eyes) diagnosed with FHI based on characteristic ocular manifestations and eight control subjects were studied. Aqueous humor (AH) samples from 14 FHI patients and one vitreous sample from a FHI patient were analyzed for intraocular antibody production against rubella virus by calculation of the Goldmann-Witmer coefficient (GWC). Viral detection by nested polymerase chain reaction and isolation by culture in RK-13 cells were conducted in nine FHI patients. In addition to laboratory examinations, medical history of rubella virus vaccination was also obtained. RESULTS: Ten patients with FHI examined showed intraocular synthesis of rubella virus antibodies (GWC > 3). A high index of rubella virus antibody production was also found in the vitreous sample (GWC = 30.6). GWC in all control subjects were below detectable level. The rubella genome was detected in two of nine patients, and rubella virus was isolated from one of nine patients with FHI. None of the patients with FHI had been vaccinated against rubella. CONCLUSIONS: Our laboratory data strongly suggest a relationship between FHI and rubella virus. PMID- 20585799 TI - Ranibizumab for diabetic macular edema difficult to treat with focal/grid laser. AB - BACKGROUND: To evaluate the efficacy of intravitreal injections of ranibizumab in patients with diabetic clinically significant macular edema (CSME), when further focal or grid laser was considered to be unsafe. METHODS: In this retrospective, interventional case study, intravitreal injections of ranibizumab were performed in 16 eyes (ten patients) suffering from diabetic retinopathy with CSME. All patients had been treated in the past with focal or grid laser. Additional photocoagulation could not be performed because the leaking points were very close to the avascular zone, and there was also a perifoveal capillary dropout. The patients underwent three injections (months 0, 1 and 2) and were followed monthly. Reinjection was performed if central retinal thickness (CRT) was >=250 MUm associated with fluorescein leakage involving the center of the macula. RESULTS: The patients underwent a median of seven injections (range 6-9) and the median follow-up time was 11 months (range 9-15). The median best-corrected visual acuity (BCVA) was 0.85 logMAR at baseline and 0.54 logMAR at the end of the follow-up time (p = 0.018). BCVA improved in seven eyes (43.75%), remained stable in eight (50%) and decreased in one eye (6.25%). The median CRT decreased from 409.5 MUm at baseline to 272 MUm at the end of the follow-up time (p = 0.0002). No ocular or systemic adverse events were reported. CONCLUSIONS: For a median follow-up time of 11 months, the treatment with intravitreal injections of ranibizumab resulted in stabilization or improvement of the visual acuity in the vast majority of patients with diabetic maculopathy and CSME, when further focal or grid laser was considered to be unsafe. PMID- 20585800 TI - The influence of surgery and intraocular lens implantation timing on visual outcome in traumatic cataract. AB - PURPOSE: To compare the visual outcome of primary versus secondary traumatic cataract extraction and primary versus secondary intraocular lens (IOL) implantation. METHODS: The medical charts of consecutive patients who developed cataract following open and closed-globe injuries and were referred to our institute were reviewed. The best-corrected visual acuity of the patients who underwent primary and secondary cataract extraction and those with primary and secondary IOL implantation was assessed at presentation and at the end of the follow-up. PARTICIPANTS: Sixty-nine eyes of 69 patients developed cataract after being involved in ocular trauma. Forty-five eyes had open-globe injury and 24 had closed-globe injury. The right eye was involved in 26 injuries and the left in 43. RESULTS: Best-corrected visual acuity (BCVA) of 20/40 or better was not statistically associated with the type of cataract extraction (extracapsular versus phacoemulsification) (in open-globe injury p = 0.181 and in all p = 0.662) and placement of anterior or posterior IOL (in open-globe injury p = 0.196 and in all p = 0.114). The timing of surgery (as immediate surgery or later as a second surgery) and the timing of intraocular lens implantation (during the extraction of the cataract or later in a secondary procedure) were not statistically associated with BCVA of 20/40 or better (in open-globe injury p = 0.322 and 0.381 in all p = 0.460 and 0.450, respectively). Irreversible amblyopia in children was a statistically significant factor for this visual acuity both in patients with open-globe injury (p = 0.036) and in all patients (p < 0.001). CONCLUSIONS: In traumatic cataract, the visual outcome did not differ between primary and secondary cataract extraction and between primary and secondary IOL implantation in adults. In the amblyogenic age, primary surgery with IOL implantation should be preferred. PMID- 20585801 TI - Stochastic modeling of the neuronal activity in the subthalamic nucleus and model parameter identification from Parkinson patient data. AB - Several stochastic models, with various degrees of complexity, have been proposed to model the neuronal activity from different parts of the human brain. In this article, we use a simple Ornstein-Uhlenbeck process (OUP) to model the spike activity recorded from the subthalamic nucleus of patients suffering from Parkinson's disease at the time of implantation of the electrodes for deep brain stimulation. From the recorded data, which contains information about the spike times of a single neuron, we identify and extract the model parameters of the OUP. We then use these parameters to numerically simulate the inter-spike intervals and the voltage across the neuron membrane. We finally assess how well the proposed mathematical model fits to the measured data and compare it with other commonly adopted stochastic models. We show an excellent agreement between the computer-generated data according to the OUP model and the measured one, as well as the superiority of the OUP model when compared to the Poisson process model and the random walk model; thus, establishing the validity of the OUP as a simple yet biologically plausible model of the neuronal activity recorded from the subthalamic nucleus of Parkinson's disease patients. PMID- 20585802 TI - Partial robotic splenectomy in hydatid disease. PMID- 20585803 TI - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): case report with a new mutation. AB - INTRODUCTION: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive multisystem disorder characterized by severe gastrointestinal dysmotility and leads to cachexia, ptosis, external ophthalmoplegia, peripheral neuropathy, and leukoencephalopathy. RESULTS AND DISCUSSION: It is often misdiagnosed as anorexia nervosa or intestinal pseudoobstuctions and are unnecessarily treated with surgery. It has been established that MNGIE is caused by mutations in the gene encoding thymidine phosphorylase, which lead to absolute or nearly complete loss of its catalytic activity, producing systemic accumulations of its substrates, thymidine and deoxyuridine. CONCLUSION: We present herein the clinical, neuroimaging, and molecular findings of a patient with MNGIE caused by a novel homozygous TYMP gene mutation (c.112G>T which convert codon 38 from glutamate to a stop codon [p.38E>X]). PMID- 20585804 TI - Microsatellite marker analysis shows differentiation among Trypanosoma cruzi populations of peripheral blood and dejections of Triatoma infestans fed on the same chronic chagasic patients : microsatellite marker analysis and T. cruzi. AB - To investigate whether Trypanosoma cruzi populations found in chagasic cardiopathic and non-cardiopathic patients are genetically differentiated, three molecular microsatellite markers were analysed. This analysis was also applied to compare T. cruzi samples from peripheral blood or dejections of Triatoma infestans fed on the blood of the same patients. In order to obtain the first objective, analyses of predominant T. cruzi genotypes were conducted using three approaches: a locus-by-locus analysis; a Fisher method across three loci; and analysis of molecular variance by Genepop and Arlequin programs. Only with one locus and on the blood samples was a significant differentiation detected among non-cardiopathic and cardiopathic groups, which was not confirmed by the other two methods. On the contrary, with the three approaches, it was found that T. cruzi clones present in the blood of patients are genetically differentiated from those detected in dejections of T. infestans fed on the same patients. Our results showed that the most frequent lineage both in blood as well as in triatomine dejection samples was TcI. No significant difference in T. cruzi lineage distribution was observed among chagasic cardiopathic and non cardiopathic patients. The majority of the samples (50-60%) had only one T. cruzi clone (uniclonal) either in blood or dejection samples. PMID- 20585805 TI - Effects of albendazole on Litomosoides chagasfilhoi (Nematoda: Filarioidea) females in vivo. AB - Gerbils (Meriones unguiculatus) experimentally infected with Litomosoides chagasfilhoi were treated with a single oral dose of 40 or 80 mg of albendazole, respectively. Observation of the microfilaremia after the treatment showed that both single oral doses of albendazole decreased the microfilaremia in L. chagasfilhoi infection. The body wall was composed of a cuticle, a hypodermis, and a muscular layer, and treated nematodes showed no morphological alterations. The ultrastructural alterations produced by treatment with 40 mg of albendazole included a higher number of membrane invaginations in the basal labyrinth of the uterine epithelium and the presence of myelin figures in this region. Inside the uterus, most embryos and microfilariae were disintegrated. The treatment with 80 mg of albendazole did not produce alterations in the uterine wall, and the number of vesicles near the microfilariae sheath was smaller than that observed in the untreated and in the 40-mg treatment groups. However, all the microfilariae observed in the uterus were extensively damaged with cytoplasmic vacuolization and cellular degeneration. No alterations in the intestinal cells were observed after treatment with 40 or 80 mg of albendazole. The present study contributes to the knowledge of albendazole's effects in filariids and demonstrates the potential embryotoxic and microfilaricidal consequences of this drug. PMID- 20585806 TI - Synthetic modified N-POMC(1-28) controls in vivo proliferation and blocks apoptosis in rat adrenal cortex. AB - The identity of the pro-opiomelanocortin (POMC)-derived mitogen in the adrenal cortex has been historically controversial. We have used well-established in vivo models, viz., hypophysectomized (Hyp) or dexamethasone (Dex)-treated rats, to study the effect of the synthetic modified peptide N-terminal POMC (N-POMC(1-28)) on DNA synthesis in the adrenal cortex, as assessed by BrdU incorporation and compared with adrenocorticotropic hormone (ACTH). We evaluated the importance of disulfide bridges on proliferation by employing N-POMC(1-28) without disulfide bridges and with methionines replacing cysteines. Acute administration of synthetic modified N-POMC(1-28) distinctly increased DNA synthesis in the zona glomerulosa and zona fasciculata, but not in the zona reticularis in Hyp rats, whereas in Dex-treated rats, this peptide was effective in all adrenal zones. ACTH administration led to an increase of BrdU-positive cells in all adrenal zones irrespective of the depletion of Hyp or Dex-POMC peptides. The use of the ACTH antagonist, ACTH(7-38), confirmed the direct participation of ACTH in proliferation. Two different approaches to measure apoptosis revealed that both peptides similarly exerted a protective effect on all adrenocortical zones, blocking the apoptotic cell death induced by hypophysectomy. Thus, ACTH(1-39) and N-POMC(1-28) have similar actions suggesting that the disulfide bridges are important but not essential. Both peptides seem to be important factors determining adrenocortical cell survival throughout the adrenal cortex, reinforcing the idea that each zone can be renewed from within itself. PMID- 20585807 TI - Increased relative abundance of an invasive competitor for pollination, Lythrum salicaria, reduces seed number in Mimulus ringens. AB - When exotic plant species share pollinators with native species, competition for pollination may lower the reproductive success of natives by reducing the frequency and/or quality of visits they receive. Exotic species often become numerically dominant in plant communities, and the relative abundance of these potential competitors for pollination may be an important determinant of their effects on the pollination and reproductive success of co-occurring native species. Our study experimentally tests whether the presence and abundance of an invasive exotic, Lythrum salicaria L. (Lythraceae), influences reproductive success of a co-flowering native species, Mimulus ringens L. (Phrymaceae). We also examine the mechanisms of competition for pollination and how they may be altered by changes in competitor abundance. We found that the presence of Lythrum salicaria lowered mean seed number in Mimulus ringens fruits. This effect was most pronounced when the invasive competitor was highly abundant, decreasing the number of seeds per fruit by 40% in 2006 and 33% in 2007. Reductions in the number of seeds per fruit were likely due to reduced visit quality resulting from Mimulus pollen loss when bees foraged on neighboring Lythrum plants. This study suggests that visit quality to natives may be influenced by the presence and abundance of invasive flowering plants. PMID- 20585808 TI - Herbivore effects on above- and belowground plant production and soil nitrogen availability in the Trans-Himalayan shrub-steppes. AB - Large mammalian herbivores may have positive, neutral, or negative effects on annual net aboveground plant production (NAP) in different ecosystems, depending on their indirect effects on availability of key nutrients such as soil N. In comparison, less is known about the corresponding influence of grazers, and nutrient dynamics, over annual net belowground plant production (NBP). In natural multi-species plant communities, it remains uncertain how grazing influences relative allocation in the above- and belowground compartments in relation to its effects on plant nutrients. We evaluated grazer impacts on NAP, NBP, and relative investment in the above- and belowground compartments, alongside their indirect effects on soil N availability in the multiple-use Trans-Himalayan grazing ecosystem with native grazers and livestock. Data show that a prevailing grazing intensity of 51% increases NAP (+61%), but reduces NBP (-35%). Grazing also reduced C:N ratio in shoots (-16%) and litter (-50%), but not in roots, and these changes coincided with increased plant-available inorganic soil N (+23%). Areas used by livestock and native grazers showed qualitatively similar responses since NAP was promoted, and NBP was reduced, in both cases. The preferential investment in the aboveground fraction, at the expense of the belowground fraction, was correlated positively with grazing intensity and with improvement in litter quality. These results are consistent with hypothesized herbivore-mediated positive feedbacks between soil nutrients and relative investment in above- and belowground compartments. Since potentially overlapping mechanisms, such as N mineralization rate, plant N uptake, compositional turnover, and soil microbial activity, may contribute towards these feedbacks, further studies may be able to discern their respective contributions. PMID- 20585809 TI - Fungal endophytes of native grasses decrease insect herbivore preference and performance. AB - Endophytic fungal symbionts of grasses are well known for their protective benefit of herbivory reduction. However, the majority of studies on endophyte grass symbioses have been conducted on economically important, agricultural species-particularly tall fescue (Lolium arundinaceum) and perennial ryegrass (Lolium perenne)-raising the hypothesis that strong benefits are the product of artificial selection. We examined whether fungal endophytes found in natural populations of native grass species deterred insect herbivores. By testing several native grass-endophyte symbiota, we examined phylogenetic signals in the effects of endophytes on insects and compared the relative importance of herbivore and symbiotum identity in the outcome of the interactions. Preference was assessed using three herbivore species [Spodoptera frugiperda (Lepidoptera), Schistocerca americana (Orthoptera), Rhopalosiphum padi (Hemiptera)] and ten native symbiota, which spanned seven grass genera. We also assessed herbivore performance in a no choice experiment for five native symbiota against S. frugiperda. We compared greenhouse and laboratory trials with natural levels of herbivory measured in experimental field populations. In all cases, we included the agronomic grass species, L. arundinaceum, to compare with results from the native grasses. Both in the field and in experimental trials, herbivores showed a significant preference for endophyte-free plant material for the majority of native grasses, with up to three times lower herbivory for endophyte-symbiotic plants; however, the degree of response depended on the identity of the herbivore species. Endophyte presence also significantly reduced performance of S. frugiperda for the majority of grass species. In contrast, the endophyte in L. arundinaceum had few significant anti-herbivore effects, except for a reduction in herbivory at one of two field sites. Our results demonstrate that the mechanisms by which native symbionts deter herbivores are at least as potent as those in model agricultural systems, despite the absence of artificial selection. PMID- 20585810 TI - Host use of a specialist lichen-feeder: dealing with lichen secondary metabolites. AB - Host use by herbivores is largely determined by host properties such as nutrient content and chemical defence against foragers. The impacts of these attributes on a herbivore may largely depend on its life cycle stage. Lichen species are known to differ in nutritional quality and level of chemical defence and, consequently, vary as fodder for herbivores. The aim of this study was to explore the impact of several lichen species and the presence of their secondary metabolites on their use as hosts by a specialist lichen-feeder, Cleorodes lichenaria. This study also addressed, for the first time, how a specialist lichen-feeder deals with different lichen secondary metabolites. In the beginning of their development, larvae grew better on Xanthoria parietina than on the other host lichens, whereas older larvae grew best on Ramalina fraxinea. Lichen secondary chemicals in R. fraxinea and Parmelia sulcata hindered larval growth in the beginning but after 75 days lichen secondary chemicals had no impact on the mass of larvae. Physodic acids in Hypogymnia physodes were lethal to larvae. In general, larvae metabolized 70-95% of ingested lichen secondary chemicals and the rest of these were excreted in frass. Lichen secondary metabolites in P. sulcata restrict and in H. physodes prevent their use as a host for C. lichenaria larvae. Our main finding, the ability of larvae to metabolize several lichen secondary metabolites, indicates digestive adaptation to these chemicals. No signs of sequestration of these chemicals were found. PMID- 20585811 TI - Gastroesophageal reflux disease. AB - GERD is a common chronic gastrointestinal disorder, and its prevalence in Asia is increasing. Classical symptoms of heartburn and regurgitation are common presentations. There is no standard criterion for the diagnosis of GERD, and 24-h pH monitoring lacks sensitivity in NERD. Furthermore, diagnostic studies for gastroesophageal reflux disease have several limitations. A short course of PPI is often used in clinical practice as a diagnostic test for gastroesophageal reflux disease. Elderly patients with GERD usually present with atypical manifestations, and they tend to develop more severe disease. PPI remains the mainstay of treatment for GERD. In a subset of patients who wish to discontinue maintenance treatment, anti-reflux surgery is a therapeutic option. PMID- 20585812 TI - Anesthetic case in a child with congenital neuromuscular disease with uniform type 1 fibers (CNMDU1). AB - Congenital neuromuscular disease with uniform type 1 fibers (CNMDU1) is an extremely rare, non-progressive, congenital neuromuscular disorder. Although the etiology is unknown, ryanodine receptor gene mutation is reportedly involved. No descriptions of anesthetic practice in patients with this disease have been reported around the world. We report a case of safe perioperative management with general anesthesia, using total intravenous anesthesia, propofol, fentanyl and a non-depolarizing muscle relaxant but avoiding the use of any inhaled anesthetics or depolarizing muscle relaxants to prevent malignant hyperthermia and postoperative respiratory failure, during anesthetic management for cranioplasty for premature synostosis of the cranial sutures in a pediatric patient of CNMDU1. PMID- 20585813 TI - Effect of single-dose dexmedetomidine on emergence agitation and recovery profiles after sevoflurane anesthesia in pediatric ambulatory surgery. AB - PURPOSE: To study the effects of dexmedetomidine (DEX), a selective alpha(2) adrenoreceptor agonist, on emergence agitation (EA), recovery profiles, and parents' satisfaction after sevoflurane anesthesia in pediatric ambulatory surgery. METHODS: In a double-blind trial, 81 children (ASA PS 1 or 2, 1-9 years) undergoing same-day or overnight-stay surgery were randomly assigned to receive intravenous DEX 0.3 MUg kg-1 (n = 39) or saline (n = 42) over 10 min after induction of anesthesia. Anesthesia was induced and maintained with sevoflurane using a facemask or laryngeal mask airway with spontaneous respiration. Agitation was assessed with a 1-4 point scale and pain with a 0-10 point scale. The patients' parents were interviewed 24 h after surgery, and adverse events and the parents' level of satisfaction with perioperative care were recorded. RESULTS: The incidence of EA (agitation scale score 3 or 4) was significantly lower in the DEX group (28%) than in the saline group (64%) (P = 0.0011). The mean pain scales in the DEX group were significantly lower than in the saline group during the stay in the post-anesthesia care unit (PACU) (P < 0.01). The incidence of adverse events, times to the first drinking and voiding in the PACU, time spent in the PACU, and parents' satisfaction level were not different between the two groups. CONCLUSION: Intravenous DEX at a dose of 0.3 MUg kg-1 after induction of anesthesia reduced sevoflurane-associated EA and postoperative pain in pediatric ambulatory surgery, with no increase in the incidence of adverse events and with no change in parents' satisfaction level. PMID- 20585814 TI - Comparison of some physical properties of finger spreaders made of stainless steel or nickel-titanium alloys. AB - The purpose of this study was to evaluate the flexibility, shape, and surface finishing of stainless steel (SS) and nickel-titanium (NiTi) finger spreaders as well as to compare the load required to insert these spreaders along a gutta percha point adapted to the apical segment of curved or straight artificial canals. Instrument flexibility was investigated by using a universal testing machine in the cantilever-flexibility test. Scanning electron microscopy (SEM) was used to examine the shape and surface finishing of different sizes of SS and NiTi finger spreaders. Penetration load was evaluated only for spreaders size C by using the universal testing machine in a compressive test. As for flexibility, the load needed to bend the SS finger spreader sizes A, B, C, and D was approximately 167%, 146%, 102%, and 64% greater than the respective sizes of NiTi finger spreaders. SEM analysis revealed that the instrument tips were always tapered, but with different vertices. NiTi spreaders showed tips with circumferential grooves; whereas, those from SS spreaders exhibited longitudinal grooves. NiTi finger spreaders required a significantly higher penetration load than SS spreaders. This difference was probably related to the different shapes and surface finishing of the instrument tips. Different characteristics of finger spreaders may result in different clinical performance during the lateral compaction technique. PMID- 20585815 TI - Muscle and joint forces under variable equilibrium states of the mandible. AB - It is well established that subjects without molars have reduced ability to comminute foods. However, epidemiological studies have indicated that the masticatory system is able to functionally adapt to the absence of posterior teeth. This supports the shortened dental arch concept which, as a prosthetic option, recommends no replacement of missing molars. Biomechanical modeling, however, indicates that using more anterior teeth will result in a larger temporomandibular joint load per unit of bite force. In contrast, changing bite from incisor to molar position increases the maximum possible bite force and reduces joint loads. There have been few attempts, however, to determine realistic joint loads and corresponding muscular effort during generation of occlusal forces similar to those used during chewing with intact or shortened dental arches. Therefore, joint and cumulative muscle loads generated by vertical bite forces of submaximum magnitude moving from canine to molar region, were calculated. Calculations were based on intraoral measurement of the feedback controlled resultant bite force, simultaneous electromyograms, individual geometrical data of the skull, lines of action, and physiological cross-sectional areas of all jaw muscles. Compared to premolar and canine biting, bilateral and unilateral molar bites reduced cumulative muscle and joint loads in a range from 14% to 33% and 25% to 53%, respectively. During unilateral molar bites, the ipsilateral joints and contralateral muscles were about 20% less loaded than the opposing ones. In conclusion, unilateral or bilateral molar biting at chewing like force ranges caused the least muscle and joint loading. PMID- 20585816 TI - Joint mobilization versus self-exercises for limited glenohumeral joint mobility: randomized controlled study of management of rehabilitation. AB - To clarify the optimal management of rehabilitative intervention for limited glenohumeral joint mobility (LGHM) arising from adhesive capsulitis, particularly focusing on the frequency of sessions for joint mobilization and the self exercise compliance, the functional results of 120 patients with LGHM were prospectively investigated as follows: Differences in improved angle of the shoulder joint (IA) and the time required to reach the range of motion plateau point (T) were compared by (1) age, (2) gender, (3) handedness, (4) duration before rehabilitative intervention, (5) frequency of sessions for joint mobilization by physical therapists in the hospital setting, and (6) self exercise compliance in the home setting. The lengths of therapy and follow-up were 4.6 and 5.9 months, respectively. IA significantly decreased in the 71-year old and above group. There were no significant differences in IA between male and female. IA of the dominant-handed group was significantly higher than that of the non-dominant-handed group. There were no significant differences in T in each item. IA of the group that had experienced more than 7 months of the condition was significantly low. Although the frequency of joint mobilization by physical therapists in the hospital setting showed no relationship with IA or T, IA was significantly higher and T was significantly shorter in the group that performed self-exercise every day than in the groups that performed less. In conclusion, early intervention and self-exercise in the home setting are more important factors than session frequency of joint mobilization in the hospital setting for the successful management of rehabilitation for LGHM. PMID- 20585817 TI - Primary progressive multiple sclerosis and generalized myasthenia gravis: an uncommon association. AB - The co-occurrence of myasthenia gravis (MG) and multiple sclerosis (MS) is rare, and in all the described cases MS had a relapsing-remitting course and the diseases had a benign clinical evolution. We describe herewith a patient with primary progressive MS (PPMS) and generalized MG with severe clinical course. This is the first report on a case of PPMS associated to MG. Studies on the histology and pathogenesis show that neurodegeneration is predominant over inflammation in PPMS, even if cellular and humoral immune-mediated mechanisms are thought to maintain a crucial importance in the development and progression of this form of disease. In the present case, the detection of cerebrospinal fluid IgM oligoclonal bands support the hypothesis of a possible role of antibody mediated immunity in PPMS and suggest that humoral immunity may take part in the concomitant development of both MS and MG. PMID- 20585818 TI - A case of mixed type of paroxysmal dyskinesia: is there an overlap between two clinical categories of paroxysmal dyskinesia? AB - We report a sporadic case of paroxysmal dyskinesia of predominantly choreic and ballistic movements of 10 years duration in a 22-year-old male. The movement starts after exercise for certain period. However, for the next 5-15 min, the movements are triggered by sudden voluntary activity. These dyskinesias persist for about 10-30 s after sudden voluntary activity. Patient has to be immobile once symptoms start after the exercise to prevent the kinesigenic involuntary movements. Involuntary movements could be induced in the lower limbs, upper limbs, facial and jaw muscle by local exercise. Overtime symptoms occurred with minimal exercise. Secondary dyskinesia was ruled out by investigations. Patient responded well to Carbamazepine, relapsed when stopped taking it. PMID- 20585819 TI - A case of subarachnoid hemorrhage with pituitary apoplexy caused by idiopathic hypertrophic pachymeningitis. AB - Steroid therapy is considered to improve clinical symptoms in hypertrophic pachymeningitis. We present a 70-year-old man with idiopathic hypertrophic pachymeningitis, whose clinical signs progressively worsened despite steroid therapy. He died of subarachnoid hemorrhage (SAH) with pituitary apoplexy 2 months after the admission regardless of improvement of laboratory data and magnetic resonance imaging appearance by one-and-half-month steroid therapy. Autopsy revealed thickened dura mater supporting the diagnosis of hypertrophic pachymeningitis. Brain parenchyma is generally not affected by the disease; however, histological investigation suggested that inflammation of the dura caused damage to superior hypophyseal artery resulting in SAH and apoplexy in the anterior lobe of the pituitary gland. The higher dose and the longer duration of steroid therapy should have achieved in our case although most laboratory data recovered within the normal range. The aggressiveness of hypertrophic pachymeningitis must be evaluated by clinical signs rather than by laboratory data or imaging examinations. PMID- 20585820 TI - Primary hypothalamic lymphoma in a patient with systemic lupus erythematosus: case report and review of the literature. AB - A 67-year-old female was admitted to our department with difficulty in speech, disorientation, memory loss and seizures. Blood laboratory tests revealed diabetes insipidus. This patient had been treated with steroids for systemic lupus erythematosus (SLE) for 30 years. Due to this treatment neurological symptoms had been understated causing a long delay in performing ulterior researches. A brain MRI revealed a mass lesion in the hypothalamic area. A biopsy was performed and histopathological diagnosis was malignant large B cell lymphoma. Subsequently, she received methotrexate therapy but died of pneumonia during the second cycle. Primary central nervous system lymphoma in association with SLE is a rare occurrence but it should be considered in the diagnostic process when neurological symptoms occur. A brain MRI must be performed and corticosteroids should be interrupted. A biopsy of the cerebral mass lesion permits diagnosis and appropriate therapy may be administered. PMID- 20585821 TI - Gd-BOPTA-enhanced MR cholangiography findings in gall bladder perforation. AB - Gall bladder perforation is a rare condition which is associated with significant mortality and morbidity. Here, we report a case of spontaneous gall bladder perforation following acute calculous cholecystitis with pericholecystic abscess identified on Gd-BOPTA-enhanced MR cholangiography (MRC) prior to laparoscopic surgery. The gall bladder perforation was confirmed via surgery with unremarkable recovery. To the best of our knowledge, this is the first report of Gd-BOPTA enhanced MRC for this purpose. PMID- 20585822 TI - Local application of gentamicin collagen implants in the prophylaxis of surgical site infections following gastrointestinal surgery: a review of clinical experience. AB - BACKGROUND: Surgical site infection (SSI) is a common type of healthcare associated infection in gastrointestinal (GI) surgical procedures, which often has major consequences for patient recovery and increased healthcare costs due to prolonged hospital stay. This article provides an overview of the efficacy and safety of prophylactic application of resorbable gentamicin-containing collagen implants (GCI) in the prevention of SSI following high-risk GI surgical procedures. METHOD: Nine publications were identified using the PubMed online database and search terms 'gentamicin collagen implant' plus 'surgical site infection', 'wound infection' and 'gastrointestinal surgery'. RESULTS: Data from 483 patients treated prophylactically have demonstrated that GCI can reduce the wound infection rate in high-risk GI surgical procedures and improve wound healing after pilonidal sinus excision. In a study of 221 patients who underwent colorectal surgery, the wound infection rate was reduced to 5.6% in the GCI group compared to 18.4% in the control group (P < 0.01). GCI also positively influences the post-operative course for patients undergoing particularly risky procedures e.g. abdominoperineal resection (APR) combined with neoadjuvant radiotherapy. In one such patient series, GCI reduced the wound infection rate by over 70% and the length of hospital stay by 40%. Few side effects of GCI were noted in the 9 clinical studies. CONCLUSIONS: This review demonstrates that GCI can have a positive effect on wound infection rates in high-risk GI surgery and can also improve wound healing after pilonidal sinus excision. PMID- 20585823 TI - Mifepristone (RU486), a pure antiprogesterone drug, in combination with vinblastine for the treatment of progesterone receptor-positive desmoid tumor. AB - We report the case of a patient who developed a desmoid tumor following total proctocolectomy and J-pouch reconstruction that was unresponsive to any medical treatment. Based on estrogen receptor alpha (ERalpha) and progesterone receptor (PR) evaluation (ERalpha-negative, but PR-positive), treatment with mifepristone, a pure antiprogesterone drug, was initiated, and partial tumor regression was achieved. PMID- 20585824 TI - Evaluation of quality of life in relation to anxiety and depression in primary Sjogren's syndrome. AB - The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with primary Sjogren's syndrome (pSS) using both Short-Form 36 (SF-36) and World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF) questionnaires and to determine the effects of anxiety and depression on HR-QOL using the Hospital Anxiety-Depression Scale (HADS). In this cross-sectional study, 107 female patients with pSS (mean age 54.10 +/- 10.2 years), fulfilling US-European Consensus Criteria and 109 female controls (mean age 53.4 +/- 10.9 years) were included. Student's t test, Mann-Whitney U test, and analysis of variance (ANOVA) were used for statistical analysis. P values > 0.05 were accepted as significant. All domains of the SF-36, with the exception of "Vitality", and all domains of the WHOQOL-BREF with the exception of "Environment", were significantly lower in pSS patients compared with healthy controls. In pSS patients having anxiety according to HADS, the scores of all domains of WHOQOL-BREF were significantly lower, and in patients having depression according to HADS, three of four domains of WHOQOL-BREF were significantly lower compared with the rest of the group. However, the scores of two domains of the SF-36, namely "Role-Physical" and "Role-Emotional" domains, were significantly higher in pSS patients having depression according to HADS. We confirmed the presence of impaired HR-QOL in pSS. Whereas the presence of anxiety and/or depression generally showed a negative affect on HR-QOL, interestingly, depression seemed to improve the scores of "Role-Physical" and "Role-Emotional" domains of the SF-36. This surprising finding might be related to adaptation to changing health. Social support based upon cultural traditions might also have contributed. PMID- 20585825 TI - Organizing pneumonia in a patient with rheumatoid arthritis treated with etanercept. AB - Etanercept-induced organizing pneumonia (OP) has not been reported in Japan. We describe the case of a rheumatoid arthritis patient who developed OP during etanercept treatment and discuss the possible mechanisms underlying the development of etanercept-induced OP and the existence of factors that predispose Japanese patients to drug-induced OP. PMID- 20585826 TI - STin2 VNTR polymorphism in the serotonin transporter gene and migraine: pooled and meta-analyses. AB - Data on the association between the SLC6A4 STin2 VNTR polymorphism and migraine are conflicting. To perform pooled and meta-analyses, we searched for studies published until September 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies. Assessment for eligibility and extraction of data was performed by two independent investigators. We extracted allele and genotype frequencies for each study. We then calculated study-specific and pooled odds ratios (OR) and 95% confidence intervals (CI) assuming allele and genotype models. We also calculated pooled ORs and 95% CIs based on study-specific effect estimates for the allele model. We included five studies investigating the association between the STin2 VNTR polymorphism and migraine. Results from the allele model suggested a protective effect against migraine for the STin2.9 and STin2.10 alleles compared to the STin2.12 allele among populations of European descent, which however was not significant. Results from the genotype model indicated a significant approximately 25% reduced risk for migraine among carriers of the 10/12 genotype compared with carriers of the 12/12 genotype among all study populations (OR = 0.76, 95% CI 0.60-0.97) for any migraine, which was more pronounced among populations of European descent (OR = 0.68, 95% CI 0.53-0.87). Results for migraine with and without aura were of similar magnitude, but were not statistically significant. Our results suggest a protective effect of non STin2.12 alleles compared to STin2.12 alleles, respectively, 10/12 and 10/10 genotypes compared to the 12/12 genotype against migraine among populations of European descent. Associations in non-European populations may differ. PMID- 20585827 TI - Focus on therapy of hypnic headache. AB - Hypnic headache (HH) is a primary headache disorder, which occurs exclusively during sleep and usually begins after 50 years of age. There are no controlled trials for the treatment of HH. We reviewed all the available papers, including 119 cases published in literature up to date, reporting the efficacy of the medications used to treat HH. Acute treatment is not recommended, since no drug proved to be clearly effective and also because the intensity and the duration of the attacks do not require the intake of a medication in most cases. As for prevention, a wide variety of medications were reported to be of benefit in HH. The drugs that were found to be effective in at least five cases are: lithium, indomethacin, caffeine and flunarizine. Lithium was the most extensively studied compound and demonstrated to be an efficacious treatment in 32 cases. Unfortunately, despite its efficacy, significant adverse effects and poor tolerability are not rare, mainly in elderly patients. Many patients reported a good response to indomethacin, but some could not tolerate it. Caffeine and melatonin treatments did not yield robust evidence to recommend their use as single preventive agents. Nevertheless, their association with lithium or indomethacin seems to produce an additional therapeutic efficacy. A course of lithium should be tried first, followed 3-4 months later by tapering. If headache recurs during tapering, a longer duration of therapy may be needed. If lithium treatment does not provide a significant response, indomethacin can be commenced as second-line approach. If these treatments prove to be ineffective or poorly tolerated, other agents, such as caffeine and melatonin, can be administered. PMID- 20585828 TI - Population structure of Nouelia insignis (Asteraceae), an endangered species in southwestern China, based on chloroplast DNA sequences: recent demographic shrinking. AB - Nouelia insignis, an endangered species, is distributed in the Jinsha and Nanpan drainage areas in southwestern China. In this study, we examined the genetic diversity and population structure based on the sequences of the cpDNA rpL 16 intron. Low levels of genetic variation were detected within all populations of the endemic species. A gene genealogy of 11 haplotypes recovered two major lineages I and II, with haplotypes H1 and H6 nested as interior nodes, respectively. Haplotype H1 was widespread in all populations, while haplotype H6 was restricted to populations southern of the Jinsha River. Low levels of genetic differentiation were detected, as most F (st) values between populations were zero. This result, however, contradicts previous studies based on allozymes and fingerprinting. Genetic analyses suggested that coancestry due to low evolutionary rates resulted in the lack of geographical subdivision. Molecular dating estimated that the two lineages split about 3.224 MYA (95% CI 1.070-6.089 MYA). Maintenance of ancestral polymorphisms was possibly attributable to a long standing large effective population size until recently. Postglacial demographic expansion was supported by a unimodal mismatch distribution and star-like phylogenies. PMID- 20585829 TI - Effectiveness of the PPARgamma agonist, GW570, in liver fibrosis. AB - INTRODUCTION: The peroxisome proliferator-activated receptors (PPARs) are well established to be important in modulating the fibrogenic response to liver injury. PPARgamma plays a role in hepatic fibrosis, presumably by virtue of its expression in hepatic stellate cells, which are key effectors of fibrosis. In this study, we evaluated whether the potent nonthiozolidinedione PPARgamma agonist, GW570, had effects on isolated stellate cells and hepatic fibrosis in vivo. METHODS: Liver fibrosis and stellate cell activation were induced in vivo by either bile duct ligation (BDL) or administration of carbon tetrachloride (CCl(4)). Primary cultures of stellate cells isolated from normal rats were exposed to GW570. The PPARgamma agonist was also given to male Sprague-Dawley rats before or during injury to test its ability to ameliorate fibrosis. Fibrosis biomarkers including total collagen, hydroxyproline, collagen I alpha1 and smooth muscle alpha actin were measured. RESULTS: GW570 had potent effects on isolated stellate cells, both simulating PPARgamma mediated gene transcription, as well as inhibiting collagen I alpha1 mRNA and protein expression and smooth muscle alpha actin protein abundance, consistent with suppression of stellate cell activation. In BDL liver injury, a daily dose of 10 mg/kg per day of GW570 inhibited collagen I alpha1 mRNA, while concentrations of 1 also inhibited fibrosis as measured by hydroxyproline and total collagen content. Lower doses of GW570 (0.1-1.0 mg/kg per day) did not significantly abrogate whole liver collagen or hydroxyproline content in this model. In a CCl(4) model, 0.1-1.0 mg/kg per day GW570 reduced expression of smooth muscle alpha actin, but did not affect whole liver collagen or hydroxyproline content. Finally, we found that GW570 had anti-inflammatory effects on Kupffer cells as well as in vivo during CCl(4) injury. CONCLUSION: PPARgamma receptor agonism with the nonthiozolidinedione, GW570, inhibited stellate cell activation in vitro and in vivo, and abrogated the fibrogenic response to injury in a dose responsive fashion. PMID- 20585830 TI - Adaptation of the xylose fermenting yeast Saccharomyces cerevisiae F12 for improving ethanol production in different fed-batch SSF processes. AB - An efficient fermenting microorganism for bioethanol production from lignocellulose is highly tolerant to the inhibitors released during pretreatment and is able to ferment efficiently both glucose and xylose. In this study, directed evolution was employed to improve the xylose fermenting Saccharomyces cerevisiae F12 strain for bioethanol production at high substrate loading. Adapted and parental strains were compared with respect to xylose consumption and ethanol production. Adaptation led to an evolved strain more tolerant to the toxic compounds present in the medium. When using concentrated prehydrolysate from steam-pretreated wheat straw with high inhibitor concentration, an improvement of 65 and 20% in xylose consumption and final ethanol concentration, respectively, were achieved using the adapted strain. To address the need of high substrate loadings, fed-batch SSF experiments were performed and an ethanol concentration as high as 27.4 g/l (61% of the theoretical) was obtained with 11.25% (w/w) of water insoluble solids (WIS). PMID- 20585831 TI - Production and optimization of carotenoid-enriched dried distiller's grains with solubles by Phaffia rhodozyma and Sporobolomyces roseus fermentation of whole stillage. AB - Whole stillage--a co-product of grain-based ethanol--is used as an animal feed in the form of dried distiller's grain with solubles (DDGS). Since animals cannot synthesize carotenoids and animal feed is generally poor in carotenoids, about 30 120 ppm of total carotenoids are added to animal feed to improve animal health, enhance meat color and quality, and increase vitamin A levels in milk and meat. The main objective of this study was to produce carotenoid (astaxanthin and beta carotene)-enriched DDGS by submerged fermentation of whole stillage. Mono- and mixed cultures of red yeasts, Phaffia rhodozyma (ATCC 24202) and Sporobolomyces roseus (ATCC 28988), were used to produce astaxanthin and beta-carotene. Media optimization was carried out in shake flasks using response surface methodology (RSM). Macro ingredients, namely whole stillage, corn steep liquor and glycerol, were fitted to a second-degree polynomial in RSM. Under optimized conditions, astaxanthin and beta-carotene yields in mixed culture and P. rhodozyma monoculture were 5 and 278, 97, and 275 MUg/g, respectively, while S. roseus produced 278 MUg/g of beta-carotene. Since the carotenoid yields are almost twice the quantity used in animal feed, the carotenoid-enriched DDGS has potential application as "value-added animal feed or feed blends." PMID- 20585832 TI - Cloning and characterization of squalene synthase gene from Fusarium fujikuroi (Saw.) Wr. AB - The gene encoding squalene synthase (GfSQS) was cloned from Fusarium fujikuroi (Gibberella fujikuroi MP-C) and characterized. The cloned genomic DNA is 3,267 bp in length, including the 5'-untranslated region (UTR), 3'-UTR, four exons, and three introns. A noncanonical splice-site (CA-GG, or GC-AG) was found at the first intron. The open reading frame of the gene is 1,389 bp in length, corresponding to a predicted polypeptide of 462 amino acid residues with a MW 53.4 kDa. The predicted GfSQS shares at least four conserved regions involved in the enzymatic activity with the SQSs of varied species. The recombinant protein was expressed in E. coli and detected by SDS-PAGE and western blot. GC-MS analysis showed that the wild-type GfSQS could catalyze the reaction from farnesyl diphosphate (FPP) to squalene, while the mutant mGfSQS (D82G) lost total activity, supporting the prediction that the aspartate-rich motif (DTXED) in the region I of SQS is essential for binding of the diphosphate substrate. PMID- 20585833 TI - Early detection of venous thromboembolism in patients with neuroepithelial tumor: efficacy of screening with serum D-dimer measurements and Doppler ultrasonography. AB - The efficacy of combined serum D-dimer level measurement and Doppler ultrasonography of the lower extremity was investigated for screening of venous thromboembolism (VTE) in patients with neuroepithelial tumor. Eighty-one patients with neuroepithelial tumor were prospectively studied. All patients underwent measurement of serum D-dimer levels and Doppler ultrasonography of the lower extremity. The serum D-dimer level was measured every week, and Doppler ultrasonography was performed two and two weeks after surgery, then every two weeks until discharge, or every two weeks for patients who did not undergo surgery. If the serum D-dimer level increased over 10.0 MUg/ml, Doppler ultrasonography or computed tomography was performed to detect VTE. VTE occurred in 12 (14.8%) patients (seven males and five females; age 34-75, mean 59.0 years). Only one patient was symptomatic, whereas 11 patients identified by the screening were without symptoms. Five patients were treated with anticoagulant therapy, one with prophylactic inferior vena cava filter placement with anticoagulant therapy, and the other six were closely followed up without medication. No patient died of pulmonary embolism. Serial Doppler ultrasonography showed thrombus regression or organization and no thrombus extension. The maximum serum D-dimer value was significantly higher in patients with VTE than in those without VTE (mean 14.5 vs. 3.46 MUg/ml, P < 0.001). The D-dimer cutoff value of 5.4 MUg/ml could be used to identify VTE with 83% sensitivity and 84% specificity. The combination of sequential serum D-dimer measurement and Doppler ultrasonography of the lower extremity is an efficient and non-invasive procedure for identifying asymptomatic VTE in patients with neuroepithelial tumor. PMID- 20585834 TI - Warfarin dosing algorithm using clinical, demographic and pharmacogenetic data from Chinese patients. AB - CYP2C9 and VKORC1 genotypes could be used to predict warfarin requirement. The objective was to develop and validate a warfarin dosing algorithm using genetic, clinical and demographic data of Chinese patients from an anticoagulation clinic in Hong Kong. Blood samples were collected from 100 patients on stable maintenance dose of warfarin, recruited from an anticoagulation clinic, for genotyping CYP2C9 and VKORC1. Clinical and demographic data were obtained by face to-face interview and medical chart review. Data of 80 patients (study cohort) were randomly selected for deriving a dosing algorithm. Comparison between predicted dose and actual stable doses was conducted in a validation cohort (n = 20). Sixty-nine (69%) of all 100 patients were homozygous for VKORC1 1173-TT, 25 (25%) were VKORC1 1173-CT heterozygotes and six (6%) were homozygous for VKORC1 1173-CC. 6 (6%) patients were CYP2C9 1*/3* and 94 (94%) were CYP2C9 1*/1*. CYP2C9 and VKORC1 genotype, age, weight and vitamin K intake were identified by stepwise regression modelling to produce the best model for estimating warfarin dose (R (2) = 68%, P < 0.001). In the validation cohort (n = 20), actual stable dose was significantly associated with predicted dose (R = 0.6, P = 0.005). Five of 11 (45.6%) and 5/9 (55.6%) patients whose mean warfarin requirements were <= 3 mg/day and >3 mg/day, respectively, were within <20% of actual doses. In conclusion, a genotype-guided dosing algorithm for warfarin therapy was developed for Chinese patients to explain 68% of dosage variation. The predicted doses differed from the actual doses by no more than 20% in 50% of patients. PMID- 20585835 TI - Oral bioaccessibility of metals in an urban catchment, Newcastle upon Tyne. AB - The metal content was determined in soils from a former, historic, contaminated land site and now a 'green' public open space in N.E. England. Using a systematic sampling grid approach, 32 soil samples were taken from locations across the site and analyzed for six potentially toxic elements (Cd, Cr, Cu, Ni, Pb, and Zn). Initially, the pseudo-total metal content of the soils was determined using acid digestion followed by inductively coupled plasma mass spectrometry analysis. This data was evaluated against published soil guideline value (SGV) and generic assessment criteria (GAC) values; it was found that 21% (i.e., 41 samples) exceeded the stated lower values. The data was then compared to the oral bioaccessibility of the soils, which was assessed by an in-vitro gastrointestinal extraction procedure. The results, determined as the % BAF, indicated that overall bioaccessibility was low (<10% BAF) for all the elements studied; the exception was Cd. Given that SGV/GAC values are based on generic land-use categories and not a public open space, as investigated in this work, further work is recommended on developing a qualitative risk assessment at the site to estimate the risks posed to human health via the direct and indirect soil ingestion pathway. PMID- 20585836 TI - Stabilization of Pb and Cd contaminated soils and soil quality improvements using waste oyster shells. AB - Large amounts of oyster shells are produced as a by-product of shellfish farming in coastal regions without beneficial use options. Accordingly, this study was conducted to evaluate the potential for the use of waste oyster shells (WOS) containing a high amount of CaCO3 to improve soil quality and to stabilize heavy metals in soil. To accomplish this, an incubation experiment was conducted to evaluate the ability of the addition of 1-5 wt% WOS to stabilize the Pb (total 1,246 mg/kg) and Cd (total 17 mg/kg) in a contaminated soil. The effectiveness of the WOS treatments was evaluated using various single extraction techniques. Soil amended with WOS was cured for 30 days complied with the Korean Standard Test method (0.1 M.HCl extraction). The Pb and Cd concentrations were less than the Korean warning and countermeasure standards following treatment with 5 wt% WOS. Moreover, the concentrations of Cd were greatly reduced in response to WOS treatment following extraction using 0.01 M.CaCl2, which is strongly associated with phytoavailability. Furthermore, the soil pH and exchangeable Ca increased significantly in response to WOS treatment. Taken together, the results of this study indicated that WOS amendments improved soil quality and stabilized Pb and Cd in contaminated soil. However, extraction with 0.43 M.CH3 COOH revealed that remobilization of heavy metals can occur when the soil reaches an acidic condition. PMID- 20585837 TI - Attachment site selection of ticks on roe deer, Capreolus capreolus. AB - The spatio-temporal attachment site patterns of ticks feeding on their hosts can be of significance if co-feeding transmission (i.e. from tick to tick without a systemic infection of the host) of pathogens affects the persistence of a given disease. Using tick infestation data on roe deer, we analysed preferred attachment sites and niche width of Ixodes ticks (larvae, nymphs, males, females) and investigated the degree of inter- and intrastadial aggregation. The different development stages showed rather consistent attachment site patterns and relative narrow feeding site niches. Larvae were mostly found on the head and on the front legs of roe deer, nymphs reached highest densities on the head and highest adult densities were found on the neck of roe deer. The tick stages feeding (larvae, nymphs, females) on roe deer showed high degrees of intrastadial spatial aggregation, whereas males did not. Male ticks showed large feeding site overlap with female ticks. Feeding site overlap between larval-female and larval-nymphal ticks did occur especially during the months May-August on the head and front legs of roe deer and might allow pathogen transmission via co-feeding. Tick density, niche width and niche overlap on roe deer are mainly affected by seasonality, reflecting seasonal activity and abundance patterns of ticks. Since different tick development stages occur spatially and temporally clustered on roe deer, transmission experiments of tick-borne pathogens are urgently needed. PMID- 20585838 TI - Ticks species (Ixodida) in the Summit Municipal Park and adjacent areas, Panama City, Panama. AB - From September 2007 to September 2009, we studied the species of ticks present in the Summit Municipal Park. Ticks were extracted from zoo animals, free-living wild mammals and reptiles trapped, dead mammals on the roads and environment (ground and zoo burrows). A total of 2,649 ticks were collected: 2,167 immature stages (1,345 larvae and 822 nymphs) and 482 adults. Seventeen species were identified: Ornithodoros puertorricensis (Argasidae), Amblyomma auricularium, A. cajennense, A. calcaratum, A. dissimile, A. geayi, A. naponense, A. nodosum, A. oblongoguttatum, A. ovale, A. pecarium, A. sabanerae, A. tapirellum, A. varium, Ixodes luciae, Haemaphysalis juxtakochi and Rhipicephalus sanguineus (Ixodidae), representing 36% of the species reported in Panama. Amblyomma ovale was the species most commonly infesting animals from the zoo. PMID- 20585839 TI - A quantitative comparison of two sample methods for collecting Amblyomma americanum and Dermacentor variabilis (Acari: Ixodidae) in Missouri. AB - In studies of tick communities, sampling methodology may influence observed patterns. The objective of this study was to compare two sampling methods, dragging and dry ice baiting, in two habitats to assess abundance of off-host ticks. Tick communities were monitored from March to December in a forested and an old-field habitat in northeast Missouri. In each habitat, eight drag and eight dry ice bait samples were collected every 2 weeks on a permanent grid. The most common ticks collected were all life stages of Amblyomma americanum L. and adult and larval Dermacentor variabilis Say. Capture data was analyzed to determine if there were differences due to sampling method, habitat or an interaction for each life stage of each species across the entire monitoring period. Data indicate that there were differences in the methods. Significantly more A. americanum nymphs were captured by bait sampling. Dragging captured significantly more larval A. americanum. Significantly more larval and nymphal A. americanum and larval D. variabilis were caught in the forest, whereas significantly more adult D. variabilis were collected in the field. Significant interaction between site and method was found for A. americanum adults and D. variabilis larvae. These differences are likely due to differences in behavior among species and developmental age that interact with microclimate. These data indicate that community monitoring studies should use multiple sampling methodologies to avoid bias. While comparing these methods, the first documented collection of off-host Ixodes scapularis Say in Adair County, Missouri was made. PMID- 20585840 TI - Molecular detection of Borrelia valaisiana-related spirochetes from Ixodes granulatus ticks in Taiwan. AB - Borrelia valaisiana-related spirochetes were detected for the first time in Ixodes granulatus ticks collected in Taiwan. The genetic identities of these detected spirochetes were determined by analyzing the gene sequences amplified by a genospecies-specific polymerase chain reaction assay based on the outer surface protein A (OspA) gene of B. burgdorferi sensu lato. Phylogenetic relationships were analyzed by comparing the sequences of OspA gene obtained from 35 strains of Borrelia spirochetes representing six genospecies of Borrelia. Eight major clades can be easily distinguished by neighbour-joining analysis and were congruent by maximum-parsimony method. Except one strain (KH-74), all these Borrelia spirochetes of Taiwan were genetically affiliated to the same clade with highly homogeneous sequences (97.8-100% similarity), and can be discriminated from other groups of B. valaisiana and other genospecies of Borrelia spirochetes with a sequence divergence ranging from 3 to 19.6%. Moreover, intraspecific analysis also revealed that three distinct groups are evident between the same species of B. valaisiana spirochetes detected in Taiwan. Our results provide the first evidence of B. valaisiana spirochetes detected in I. granulatus ticks collected in Taiwan and demonstrate that all these B. valaisiana spirochetes of Taiwan represent three major groups distinct from the European group of B. valaisiana spirochetes. PMID- 20585841 TI - A novel amino acid substitution in the para-sodium channel gene in Rhipicephalus microplus (Acari: Ixodidae) associated with knockdown resistance. AB - Resistance acquired by the tick Rhipicephalus microplus (Canestrini) to different types of ixodicides in Mexico has had a negative impact on national and local livestock, mainly due to the transmission of diseases such as babesiosis and anaplasmosis, among others. The technique used for the diagnosis of resistance was that in the bioassays noted in the Norma Oficial Mexicana (NOM-006-ZOO-1994). The purpose of this investigation was the determination of resistance to pyrethroids through isoleucine-phenylalanine mutation in the gene KDR, in a population of ticks from Montemorelos, NL, Mexico. Preliminary bioassays demonstrated resistance to cypermethrin and deltamethrin (27.4%) and flumethrin (36.7-34.7%). To identify the mutation, DNA was extracted from 100 mg of larvae (pools), 10 pools were assessed by PCR, in which a pair of primers designed with the program Oligo 2.0 and Amplify 1.2 amplified a 136 bp fragment containing the mutation. The PCR product was subsequently sequenced to confirm the presence of the mutation. A strain susceptible to pyrethroid insecticides (Mora strain) was used as control, but it did not show the mutation. However, the mutation was detected in 4 out of 10 samples of the strain Montemorelos. PMID- 20585842 TI - Effect of crystal size on the in vitro dissolution and oral absorption of nitrendipine in rats. AB - PURPOSE: To investigate the effect of crystal size on the dissolution and oral absorption of nitrendipine, a poorly soluble drug, in rats. METHODS: Five types of nitrendipine crystal suspensions with different particle sizes (200 nm, 620 nm, 2.7 microm, 4.1 microm, 20.2 microm) were prepared either by the precipitation-ultrasonication or the anti-solvent precipitation method. The simulated intestinal fluid in the fasted state (FaSSIF) was selected as the dissolution medium, and the dissolution behaviors of different nitrendipine crystals were simulated based on a Noyes-Whitney type equation. The in vivo absorption and the absolute bioavailability of the different nitrendipine crystals were evaluated in Wistar rats. RESULTS: The dissolution rate of nitrendipine was significantly increased by a reduction in particle size. The dissolution test in FaSSIF could discriminate between the differences in the dissolution rates of the different particle sizes, and the simulated results were in agreement with the observed dissolution curves. From the simulated T(50%) values (50% dissolution time), the dissolution rates of crystals with particle sizes of 200 nm, 620 nm, 2.7 microm, 4.1 microm and 20.2 microm were calculated to be 5.1 x 10(4), 1.0 x 10(4), 237, 64 and 11-fold greater than that of the raw crystals and resulted in absolute bioavailability of 61.4% 51.5%, 29.4%, 26.7%, 24.7%, respectively. The reduction in the drug particle size correlated well with incremental improvements in oral absorption. A good linear relationship was observed between the Log (T(50%)) and the absolute bioavailability of nitrendipine. CONCLUSIONS: The dissolution rate and the oral bioavailability of nitrendipine were significantly affected by the crystal size, and the oral bioavailability could be improved significantly by preparing it as nanocrystals. FaSSIF can be used to predict differences in oral absorption of crystals with different particle sizes. PMID- 20585843 TI - Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance. AB - PURPOSE: Hepatocellular carcinoma (HCC) is a prevalent solid malignancy. Critically needed discovery of new therapeutics has been hindered by lack of an in vitro cell culture system that can effectively represent the in vivo tumor microenvironment. To address this need, a 3D in vitro HCC model was developed using a biocompatible, chitosan-alginate (CA) scaffold cultured with human HCC cell lines. METHODS: The correlation between the cell function, such as secretion of growth factors and production of ECM in vitro, and the tumor growth and blood vessel recruitment in vivo was investigated. RESULTS: HCC cells grown on 3D CA scaffolds demonstrated morphological characteristics and increased expression of markers of highly malignant cells. Implantation of CA scaffolds cultured with human HCC cells in mice showed accelerated tumor growth. Histology revealed marked differences in morphology and organization of newly formed blood vessels between tumors produced by different pre-cultured conditions. Resistance to doxorubicin was significantly pronounced in CA scaffold-cultured HCC cells compared to 2D or Matrigel cultured HCC cells. CONCLUSIONS: This 3D model of HCC, with its ability to more closely mimic the in vivo tumor behavior, may serve as an invaluable model for study and application of novel anticancer therapeutics against HCC. PMID- 20585844 TI - Leachables from saline-containing IV bags can alter therapeutic protein properties. AB - PURPOSE: To investigate the cause of the observed instability of dulanermin in 100 ml polyolefin (PO) infusion bags containing saline. METHODS: Diluted dulanermin in IV bags was collected and frozen prior to analysis by size exclusion chromatography. The UV absorption profiles of the IV bag solutions were characterized by using spectrophotometry. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) measured the metal content. Leachables from IV bags were identified by LC-UV-high resolution MS/MS analysis. RESULTS: An elevated loss of dulanermin monomers was observed only in 100 ml PO bags. These IV bag solutions have a compound that contains zinc and has absorbance at 320 nm. This compound was identified to be 2-Mercaptobenzothiazole, and its zinc salt and was found to come from the stopper used in the 100 ml PO bags. The manufacturer has subsequently corrected this problem by using non-latex components in the 100 ml PO IV bag. CONCLUSIONS: End-users need to be aware that IV bags made from a particular polymer by the same manufacturer may contain components or use a manufacturing process that results in a different product. Analysis of samples after freezing and thawing proved to be useful in identifying potential incompatibility of dulanermin in the IV bags. PMID- 20585845 TI - Characterisation and prediction of phase separation in hot-melt extruded solid dispersions: a thermal, microscopic and NMR relaxometry study. AB - PURPOSE: To develop novel analytical approaches for identifying both miscibility and phase separation in hot-melt extruded formulations. METHODS: Felodipine Eudragit E PO solid dispersions were prepared using hot-melt extrusion. The fresh and aged formulations were characterised using scanning electron microscopy, differential scanning calorimetry, heat capacity (C(p)) measurements using modulated temperature DSC and nuclear magnetic resonance relaxometry. RESULTS: The solubility of the drug in polymer was predicted as being < or =10% w/w using a novel model proposed in this study. Freshly prepared HME formulations were found to show no evidence for phase separation despite drug loadings greatly in excess of this figure. Conventional DSC showed limitations in directly detecting phase separation. However, a novel use of C(p) measurements indicated that extensive phase separation into crystalline domains was present in all aged samples, a conclusion supported by SEM studies. The NMR relaxometry study confirmed the existence of phase separation in all aged formulations and also allowed the estimation of separated domains sizes in different formulations. CONCLUSIONS: This study has presented a series of novel approaches for the identification, quantification and prediction of phase separation in HME formulations. Supersaturation of drug in the polymer caused the phase separation of the aged felodipine-Eudragit E PO formulations. PMID- 20585847 TI - Are ADHD traits dissociable from the autistic profile? Links between cognition and behaviour. AB - Reports of co-morbid symptoms of ADHD in children with ASD have increased. This research sought to identify ADHD-related behaviours in a sample of children with ASD, and their relationship with the ASD triad of impairments and related cognitive impairments. Children with ASD (n = 55) completed a comprehensive cognitive assessment whilst a semi-structured parental interview (3Di) provided information on ASD and ADHD symptoms. Co-morbid presentation of ADHD traits in these participants was associated with reports of more ASD related behaviours. Inhibitory control performance was directly related only to the ADHD symptom of impulsive behaviour. In contrast, while there was a relationship between social difficulties associated with ASD and theory of mind ability, there was no such relationship with behaviours relating to ADHD. PMID- 20585849 TI - Expression of the stem cell marker ALDH1 in the normal breast of BRCA1 mutation carriers. PMID- 20585848 TI - Roles of TRAF2 and TRAF3 in Epstein-Barr virus latent membrane protein 1-induced alternative NF-kappaB activation. AB - Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)-induced NF-kappaB activation is essential for EBV-transformed B cell survival. LMP1 has two C terminal cytoplasmic domains referred to as C-Terminal Activation Regions (CTAR) 1 and 2 that activate the alternative and canonical NF-kappaB pathways, respectively. While CTAR2 activates TRAF6, IKKbeta and IKKgamma-dependent canonical NF-kappaB pathway, CTAR1 interacts with TRAF2 and TRAF3 and activates NIK and IKKalpha-dependent alternative NF-kappaB pathway involving p100 processing into functional p52. Using IKKalpha(-/-), IKKbeta(-/-), IKKgamma(-/-), TRAF2(-/-), TRAF3(-/-), TRAF6(-/-), and NIK(aly/aly) mouse embryonic fibroblasts (MEFs), potential roles of these proteins in LMP1-induced alternative NF-kappaB activation were investigated. Deficiency in IKKalpha or functional NIK, but not in IKKbeta, IKKgamma, or TRAF6, severely impaired LMP1-induced p100 processing. Notably, p100 was constitutively processed in TRAF2(-/-) or TRAF3(-/-) MEFs independently of LMP1 suggesting that TRAF2 or TRAF3 may play a regulatory role in p100 processing. Subsequently, TRAF2 or TRAF3 over-expression in HEK293 cells significantly blocked LMP1-induced p100 processing. The LMP1 CTAR1 expression in 293HEK cells activated the alternative p65/p52 complex while CTAR2 failed to do so. Taken together, LMP1 activates alternative NF-kappaB pathway through functional NIK and IKKalpha that is regulated by TRAF2 or TRAF3. PMID- 20585850 TI - Gene expression profile predicts outcome after anthracycline-based adjuvant chemotherapy in early breast cancer. AB - Prognosis of early beast cancer is heterogeneous. Today, no histoclinical or biological factor predictive for clinical outcome after adjuvant anthracycline based chemotherapy (CT) has been validated and introduced in routine use. Using DNA microarrays, we searched for a gene expression signature associated with metastatic relapse after adjuvant anthracycline-based CT without taxane. We profiled a multicentric series of 595 breast cancers including 498 treated with such adjuvant CT. The identification of the prognostic signature was done using a metagene-based supervised approach in a learning set of 323 patients. The signature was then tested on an independent validation set comprising 175 similarly treated patients, 128 of them from the PACS01 prospective clinical trial. We identified a 3-metagene predictor of metastatic relapse in the learning set, and confirmed its independent prognostic impact in the validation set. In multivariate analysis, the predictor outperformed the individual current prognostic factors, as well as the Nottingham Prognostic Index-based classifier, both in the learning and the validation sets, and added independent prognostic information. Among the patients treated with adjuvant anthracycline-based CT, with a median follow-up of 68 months, the 5-year metastasis-free survival was 82% in the "good-prognosis" group and 56% in the "poor-prognosis" group. Our predictor refines the prediction of metastasis-free survival after adjuvant anthracycline-based CT and might help tailoring adjuvant CT regimens. PMID- 20585851 TI - Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. AB - In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2 negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28 day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study. PMID- 20585852 TI - Pollution caused by peoples' use for socio-economic purposes (agricultural, recreation and tourism) in the Golcuk Plain Settlement at Bozdag Plateau (Odemis Izmir/Turkey): a case study. AB - Mountainous areas, which form the largest geography of our country and are called reserves of resources owing to their difficulty of accessibility, have been increasingly under threat of exploitation and overuse in recent years. The area in question from among the mountainous areas, which are sensitive ecosystems with their environmental components, is the Bozdag mass located in Golcuk Plateau Settlement, which has been subject to intensive construction and use. This study is intended to reveal the current uses of Golcuk Plateau (agricultural, recreation, and tourism) and determine the sources and effects of pollution as a result of these uses and aims at revealing how the permanent residents of Golcuk Plateau Settlement on Bozdag Plateau, which is a center of attraction with respect of recreation and tourism activities, and those who go there only in certain periods, use the environment for tourism and recreational purposes, and determine their positive and negative impacts on environment through SWOT analysis. PMID- 20585853 TI - Cardiac remodelling, blood chemistry, haematology and oxygen consumption of Atlantic cod, Gadus morhua L., induced by experimental haemolytic anaemia with phenylhydrazine. AB - Anaemia is a common pathology associated with many infectious and non-infectious diseases. The effects of haemolytic anaemia induced by i.p. injection of phenylhydrazine (PHZ) were studied in Atlantic cod. Phenylhydrazine injection (0.3 mg kg(-1)) in a DMSO and saline vehicle induced a reproducible and stable anaemia reducing haematocrit, (Hct) by 62% over 3 weeks. Controls consisted of fish injected with saline and DMSO/saline vehicle with minimal effects on Hct or whole blood haemoglobin (Hb). Although anaemia resulted in reduced blood lactate and glucose in PHZ injected fish, there were no effects of anaemia on blood, sodium, chloride or potassium. Similarly, there were no changes in the relative proportions of leucocytes in the blood although an increase in the number of immature erythrocytes was observed in the anaemic fish. Anaemic fish showed a 29 and 22% increase in cardiac somatic index (CSI) relative to saline and vehicle controls, respectively, although there were no significant differences in the linear dimensions of the ventricle. Changes in cardiac somatic and ventricular somatic index correlated positively and significantly with Hct but not with whole blood Hb concentration. Anaemic fish had significantly reduced resting routine oxygen consumption compared with vehicle controls but were not able to increase oxygen consumption following a bout of exhaustive exercise. Plasma lactate concentrations increased significantly after exercise to a greater extent in anaemic fish compared with vehicle control fish. Phenylhydrazine is a useful model for studying haemolytic anaemia in Atlantic cod with minimal effects on blood biochemistry and haematology and clearly reduces the aerobic capacity in Atlantic cod. PMID- 20585854 TI - The home dialysis first paradigm: suitability and transitioning. PMID- 20585855 TI - Survey of ectomycorrhizal, litter-degrading, and wood-degrading Basidiomycetes for dye decolorization and ligninolytic enzyme activity. AB - Basidiomycetes are essential in forest ecology, being deeply involved in wood and litter decomposition, humification, and mineralization of soil organic matter. The fungal oxidoreductases involved in these processes are today the focus of much attention with a view to their applications. The ecological role and potential biotechnological applications of 300 isolates of Basidiomycetes were assessed, taking into account the degradation of model dyes in different culture conditions and the production of oxidoreductase enzymes. The tested isolates belong to different ecophysiological groups (wood-degrading, litter-degrading, ectomycorrhizal, and coprophilous fungi) and represent a broad systematic and functional biodiversity among Basidiomycetes occurring in deciduous and evergreen forests of northwest Italy (Piedmont Region). The high number of species tested and the use of different culture conditions allowed the investigation of the degradation activity of several novel species, neglected to date. Oxidative enzyme activities varied widely among all ecophysiological groups and laccases were the most commonly detected enzymes. A large number of isolates (86%), belonging to all ecophysiological groups, were found to be active against at least one model dye; the wood-degrading fungi represented the most efficient group. Noteworthily, also some isolates of litter-degrading and ectomycorrhizal fungi achieved good decolorization yield. The 25 best isolates were then tested against nine industrial dyes commonly employed in textile industries. Three isolates of Bjerkandera adusta efficiently decolorized the dyes on all media and can be considered important candidates for application in textile wastewater treatment. PMID- 20585856 TI - Creating prebiotic sanctuary: self-assembling supramolecular Peptide structures bind and stabilize RNA. AB - Any attempt to uncover the origins of life must tackle the known 'blind watchmaker problem'. That is to demonstrate the likelihood of the emergence of a prebiotic system simple enough to be formed spontaneously and yet complex enough to allow natural selection that will lead to Darwinistic evolution. Studies of short aromatic peptides revealed their ability to self-assemble into ordered and stable structures. The unique physical and chemical characteristics of these peptide assemblies point out to their possible role in the origins of life. We have explored mechanisms by which self-assembling short peptides and RNA fragments could interact together and go through a molecular co-evolution, using diphenylalanine supramolecular assemblies as a model system. The spontaneous formation of these self-assembling peptides under prebiotic conditions, through the salt-induced peptide formation (SIPF) pathway was demonstrated. These peptide assemblies possess the ability to bind and stabilize ribonucleotides in a sequence-depended manner, thus increase their relative fitness. The formation of these peptide assemblies is dependent on the homochirality of the peptide monomers: while homochiral peptides (L-Phe-L-Phe and D-Phe-D-Phe) self-assemble rapidly in aqueous environment, heterochiral diastereoisomers (L-Phe-D-Phe and D Phe-L-Phe) do not tend to self-assemble. This characteristic consists with the homochirality of all living matter. Finally, based on these findings, we propose a model for the role of short self-assembling peptides in the prebiotic molecular evolution and the origin of life. PMID- 20585857 TI - A grounded theory study of spirituality: using personal narratives suggested by spiritual images. AB - This study expanded on traditional concepts of spirituality through an analysis of narratives derived from images with spiritual content. Twenty-five participants were selected based on their being actively involved in spiritual practices. They were requested to tell TAT-type stories to a series of twelve images that revolved around spiritual themes. The resulting 300 stories were coded according to Grounded Theory procedures. A theory of spirituality emerged that centered upon the expression of suffering and the expectation of it being relieved. Results suggest that the personal spiritual process is one that expects and seeks transformation of the suffering through a connection with another, a connection with the transcendent, acquiring wisdom, or transforming the internal state. PMID- 20585858 TI - "I don't have a home:" helping homeless people through faith, spirituality, and compassionate service. PMID- 20585859 TI - Preliminary report on a sonographic method to determine the location of the intimal breach in Stanford type B aortic dissection. AB - Using a defined angle T, which can be measured noninvasively using Doppler ultrasound, we aim to determine the location of the intimal breach in Stanford type B aortic dissection (AD) and estimate the risk of AD using that measurement. Our subjects included 86 healthy volunteers, 60 hypertensive patients, and 42 patients with Stanford type B AD. We used dual functional color Doppler ultrasound to locate the central point of the high-speed flow zone within the descending aorta, and then calculated the angle T, using the law of cosines. In addition, we measured the degree of distortion within the descending aorta using Line BD, defined as the distance from the lateral edge of the left subclavian artery (LSA) to the center of the breach in the intima in AD. The value of T was approximately 24 degrees +/- 3 degrees and was constant across all 3 groups. In addition, the increase in BD distance corresponded to increased distortion in the descending aorta between the LSA and the region of aortic artery ligament (RAALE). We found that when the preoperative BD was less than 2.6 cm, the aortic arch could be straightened, using a stent-graft, to approximate the normal aorta. When the preoperative BD is less than 2.6 cm, the aortic arch can be corrected using a stent. In addition, since the T angle is constant, we speculate that it can be used to predict the risk of intimal breach and estimate its location using digital subtraction angiography (DSA) to guide surgery. PMID- 20585860 TI - Atherosclerotic plaque components characterization and macrophage infiltration identification by intravascular ultrasound elastography based on b-mode analysis: validation in vivo. AB - Intravascular ultrasound elastography (IVUSE) is a promising imaging technique for early investigation of vulnerable plaques. Compared to radiofrequency signal processing, digital B-mode analysis is simple and of higher portability. However, rare studies have been reported validating the latter technique in vivo. In this study, we developed an IVUSE computer software system involving semi-automatic border delineation and block-matching algorithm and validated the system in vivo. Seven minipigs were fed with atherogenic diet for 40 weeks. For each pig, the endothelium of one side of the renal arteries was denuded at the fifth week. With cross-correlation analysis, Lagrangian strain was calculated from two intravascular ultrasound images acquired in situ. Sixty regions of interests were selected from 35 elastograms matched well with the corresponding histological slices. Plaque types within these regions were classified as fibrous, fibro-fatty or fatty on Masson's trichrome and Oil-red O staining. Macrophage infiltration was also evaluated with immunohistology. Comparison between the mean strain value of the region of interest and the histological results revealed significant differences in strain values among different plaque types and non-diseased artery walls. The extent of macrophage infiltration was found to be correlated positively with strain values. For identification of fibro-fatty and fibrous plaques and macrophage infiltration, the system showed high sensitivity (93, 96 and 92%, respectively) and specificity (89, 76 and 66%, respectively), as revealed by receiver operating characteristic analysis. Our IVUSE system based on B-mode analysis is capable of characterizing fibrous and fibro-fatty plaques and macrophage intensity, thus holds potential for identifying vulnerable plaque. PMID- 20585861 TI - Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy. AB - Cardiac fibrosis plays an important prognostic role in nonischemic cardiomyopathy (NICM), making it a potential therapeutic target. Although electromechanical mapping has been used to identify myocardial scar and facilitate intramyocardial intervention in the setting of ischemic heart disease, its application has not been described in NICM. We assessed the detection of myocardial fibrosis by endoventricular electromechanical mapping in an experimental model of NICM. The NOGA(r) XP system was used to perform left ventricular mapping in twelve sheep that had undergone intracoronary doxorubicin dosing to induce NICM and in six healthy control animals. Results for endocardial voltage and mechanical shortening were evaluated against myocardial fibrosis burden, as determined by delayed-enhancement cardiac magnetic resonance and quantitative histomorphometry. Doxorubicin treatment resulted in dilated cardiomyopathy with moderate-severe impairment of left ventricular ejection fraction. Late gadolinium uptake was present in 9/12 doxorubicin animals, while histological fibrosis was approximately doubled compared to controls and was distributed multisegmentally throughout the left ventricle. Cardiomyopathy was associated with widespread reductions in unipolar and bipolar voltage amplitude and endocardial shortening. Each parameter showed an inverse relationship with the burden of fibrosis. Moreover, unipolar voltage and linear local shortening ratio displayed moderate accuracy for identifying myocardial segments with delayed contrast enhancement or increased fibrosis content, with optimal discriminatory thresholds of 7.5 mV and 11.5%, respectively. In this model of NICM, electromechanical mapping shows potential for delineating segmental differences in fibrosis. Pending clinical evaluation, it may therefore have applicability for directing targeted intramyocardial interventions in nonischemic heart disease. PMID- 20585862 TI - Utility of 64 detector coronary computed tomographic angiography in patients with and without prior equivocal stress tests. AB - This study sought to compare and the utility of cardiac computed tomographic angiography (CCTA) in patients with and without prior equivocal stress testing, and the subsequent need for invasive angiography and revascularization after CCTA. Evidence for the clinical utility of CCTA in the assessment of low to intermediate risk patients with equivocal stress testing is limited. Consecutive patients referred for outpatient CCTA for evaluation of suspected CAD with and without prior equivocal stress testing were included. CCTA studies were performed on a 64 detector scanner (Toshiba Aquilion). The diagnostic yield of CCTA for coronary stenoses and the subsequent need of the patients for invasive angiography and revascularization was evaluated. Of 228 patients evaluated, 43.9% were male, average age 59.3 +/- 10.3. 66.2% (n = 151) had an equivocal stress test prior to CCTA. The prevelance of significant lesions (>50% stenosis) was high at 31% (n = 71), and was similar for those with and without a prior equivocal stress test (29.1 vs. 35.0%, P = NS). During a mean follow up of 1.4 +/ 0.4 years, all patients with normal or stenosis by CCTA of <50% remained free from revascularization. Among those with a >50% stenosis by CCTA, the revascularization rate was 33.8%. The rates of angiography and revascularization were similar in those with or without prior stress tests (19 vs. 27%, P = 0.13 and 12 vs. 7.8%, P = 0.34 respectively). Regardless of whether or not patients had prior equivocal stress tests, CCTA detected a substantial number of obstructive CAD lesions and effectively identified the need for subsequent invasive angiography and revascularization. It appears to be a very promising triage test in this population. PMID- 20585863 TI - Development and characterization of a scalable microperforated device capable of long-term zero order drug release. AB - A drug delivery system that consists of microperforated polyimide microtubes was developed and characterized. Two groups of polyimide tubes were used. One set consisted of microtubes (I.D. = 125 microm) with 32.9 +/- 1.7 microm size holes. The second set consisted of larger tubes (I.D. = 1000 microm) with 362-542 microm holes. The number of holes was varied between 1 and 3. The small tubes were loaded with crystal violet (CV) and ethinyl estradiol (EE) and the drug release studies were performed in 0.01 M phosphate buffered saline (PBS) (pH 7.1-7.4) at 37.0 +/- 1.0 degrees C for upto 4 weeks. The large tubes were loaded with CV and the drug release was studied in vitro in PBS and also ex vivo in rabbit's vitreous humor. Linear release rates with R(2) > 0.9900 were obtained for all groups with CV and EE. Release rates of 7.8 +/- 2.5, 16.2 +/- 5.5, and 22.5 +/- 6.0 ng/day for CV and 30.1 +/- 5.8 ng/day for EE were obtained for small tubes. For large tubes, a release rate of 10.8 +/- 4.1, 15.8 +/- 4.8 and 22.1 +/- 6.7 microg/day was observed in vitro in PBS and a release rate of 5.8 +/- 1.8 microg/day was observed ex vivo in vitreous humor. PMID- 20585864 TI - Reclassification of two peronospora species parasitic on draba in hyaloperonospora based on morphological and molecular phylogenetic data. AB - On the family Brassicaceae, the causal agent responsible for downy mildew disease was originally regarded as a single species, Peronospora parasitica (now under Hyaloperonospora), but it was recently reconsidered to consist of many distinct species. In this study, 11 specimens of Peronospora drabae and P. norvegica parasitic on the genus Draba were investigated morphologically and molecularly. Pronounced differences in conidial sizes (P. drabae: 14-20 * 12.5-15.5 MUm; P. norvegica: 20-29 * 15.5-22 MUm) and 7.8% sequence distance between their ITS1 5.8S-ITS2 rDNA sequences confirmed their status as distinct species. Based on ITS phylogeny and morphology (monopodially branching conidiophores, flexuous to sigmoid ultimate branchlets, hyaline conidia and lobate haustoria), the two species unequivocally belong to the genus Hyaloperonospora and not to Peronospora to which they were previously assigned. Therefore, two new combinations, Hyaloperonospora drabae and H. norvegica, are proposed. The two taxa are illustrated and compared using the type specimen for H. norvegica and authentic specimens for H. drabae, which is lectotypified. PMID- 20585865 TI - Para-aortic lymphadenectomy in the management of preoperative grade 1 endometrial cancer confined to the uterine corpus. AB - BACKGROUND: The aim of this study was to determine the risk of para-aortic lymph node metastasis in surgically staged patients presenting with preoperative grade 1 endometrial cancer and to assess the impact of para-aortic lymphadenectomy. MATERIALS AND METHODS: A total of 131 consecutive patients diagnosed with preoperative grade 1 endometrial cancer from 2004 to 2009 were analyzed. We included women with endometrial cancer that was thought preoperatively to be confined to the uterine corpus, and all patients had complete staging operation including total hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, pelvic lymphadenectomy, and para-aortic lymphadenectomy. RESULTS: Of 131 patients, 6 (4.6%) had positive para-aortic lymph nodes and only 2 (1.5%) had isolated para-aortic nodal metastasis with negative pelvic nodes. In comparison of preoperative and postoperative histology, 6.8% of patients were upgraded, with 5.3% grade 2 and 1.5% grade 3. Advanced stage disease was found in 12.9%. Deep myometrial invasion by MRI and CA 125 levels of >= 31 U/ml were found to be independent preoperative risk factors for para-aortic lymph node metastasis. CONCLUSIONS: Some patients with preoperative grade 1 endometrial cancer are found to have upgraded disease and para-aortic nodal metastasis. Para-aortic lymphadenectomy should be considered in patients presenting with preoperative grade 1 endometrial cancer, especially in the setting of preoperative CA 125 levels of > 31 U/ml and deep myometrial invasion by MRI. PMID- 20585866 TI - Metaplastic breast cancer: to radiate or not to radiate? AB - BACKGROUND: The role of radiation therapy (RT) is unclear for metaplastic breast cancer (MBC). We hypothesized that RT would improve overall survival (OS) and disease-specific survival (DSS). MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify MBC patients diagnosed from 1988 to 2006. Univariate analyses of patient, tumor, and treatment-specific factors on OS and DSS were performed using the Kaplan-Meier method and differences among survival curves assessed via log rank. Variables assessed included patient age, race/ethnicity, histologic subtype, tumor grade, T stage, N stage, M stage, hormone receptor status, surgery type, and use of RT. Cox proportional hazards models used all univariate covariates. Risks of mortality were reported as hazard ratios (HR) with 95% confidence intervals (95% CI); significance was set at P <= 0.05. RESULTS: Among 1501 patients, RT was given to 580 (38.6%). Ten-year OS and DSS were 53.2, and 68.3%, respectively. In the overall analysis, RT provided an OS (HR 0.64; 95% CI, 0.51-0.82; P < 0.001) and DSS (HR 0.74; CI, 0.56-0.96; P < 0.03) benefit. When patients were stratified according to type of surgery, RT provided an OS but not a DSS benefit to lumpectomy (HR 0.51; CI, 0.32-0.79, P < 0.01) and mastectomy patients (HR 0.67; CI, 0.49-0.90; P < 0.01). CONCLUSIONS: Our findings support the use of RT for patients with MBC following lumpectomy or mastectomy. These retrospective findings should be confirmed in a prospective clinical trial. PMID- 20585867 TI - Influence of neoadjuvant chemoradiation on the number and size of analyzed lymph nodes in esophageal cancer. AB - BACKGROUND: Studies have shown that along with primary tumor response, lymph node status after RTx/CTx is one of the most important prognostic factors for advanced esophageal carcinoma. The goal of our study was to investigate the influence of neoadjuvant radiochemotherapy (RTx/CTx) on lymph nodes (LN). MATERIALS AND METHODS: From 1997 until 2006, 297 patients underwent surgery for advanced esophageal carcinoma. Of these, 192 received preoperative chemoradiation (5-FU, cisplatin, 36 Gy). The following matched subgroups were chosen: Group I, 20 with surgery alone: 10 adenocarcinoma (AC), 10 squamous cell carcinoma (SCC); Group II, 20 with minor response (10 AC, 10 SCC); Group III, 20 with major response (10 AC, 10 SCC). Tumor response was graded as "minor" or "major" according to the Cologne Regression Scale, the LN size determined by the largest measured diameter. RESULTS: A total of 1967 LNs from 60 patients were examined. Of these, 161 LNs showed metastasis. The median number of LNs examined per patient was not significantly higher in group I compared with the group with pretreatment (32 vs 31). Group I and group II showed LN metastasis (LNM) in 65% of cases, and group III in only 20% (p = 0.011). LNMs after pretreatment had significantly smaller median diameters (5.0 mm) than those without (7.0 mm) (p < 0.02). Nonmetastatic LN size did not vary between the three groups. LN size with and without metastasis did not differ between AC and SCC or between major and minor responders. CONCLUSION: With good response to neoadjuvant radiochemotherapy, the size and the number of metastatic LNs is significantly reduced regardless of histologic cancer type. PMID- 20585868 TI - Immediate microvascular breast reconstruction after neoadjuvant chemotherapy: complication rates and effect on start of adjuvant treatment. AB - BACKGROUND: The effect of neoadjuvant chemotherapy on immediate microvascular breast reconstruction is of concern because any complication might delay adjuvant treatment. We sought to determine whether the complication rate is increased and whether the interval between surgery and subsequent treatment is delayed compared with patients without neoadjuvant chemotherapy. METHODS: Complication rates and interval from surgery until adjuvant treatment of patients with mastectomy for locally advanced breast cancer followed by immediate microvascular breast reconstruction (deep inferior epigastric perforator (DIEP) flap, transverse rectus abdominis musculocutaneous (TRAM) flap, superior gluteal artery perforator (SGAP) flap, transverse musculocutaneous gracilis (TMG) flap, or superficial inferior epigastric artery (SIEA) flap) after neoadjuvant chemotherapy were compared with those of patients who underwent immediate breast reconstruction without neoadjuvant chemotherapy. RESULTS: Forty-seven patients with locally advanced breast cancers who underwent neoadjuvant chemotherapy before mastectomy and immediate microvascular reconstruction and 52 patients without neoadjuvant chemotherapy were identified. 36% of patients with neoadjuvant chemotherapy had one or more complications compared with 29% of patients without previous chemotherapy, but this difference was not statistically significant. The occurrence of complications in patients with neoadjuvant chemotherapy did not result in a delayed start of adjuvant treatment compared with patients without complications after neoadjuvant chemotherapy (43.6 vs. 44.6 days). CONCLUSIONS: Immediate microvascular breast reconstruction after neoadjuvant chemotherapy does not result in an increased complication rate or delay the start of adjuvant treatment even if complications occur and therefore can be performed safely in patients with locally advanced breast cancer. PMID- 20585869 TI - Prognostic implication of ezrin overexpression in myxofibrosarcomas. AB - BACKGROUND: The bases of tumorigenesis, progression, and metastasis remain obscure in myxofibrosarcoma. As a member of ezrin-radixin-moesin family, ezrin acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It is implicated in tumor progression and metastatic dissemination, and it is associated with adverse outcomes in several cancer types, including pediatric sarcomas. METHODS: Ezrin immunostain could be assessed from tissue microarrays of 78 cases of primary localized myxofibrosarcomas and correlated with clinicopathological factors and patient survival. In two myxofibrosarcoma cell lines, ezrin mRNA expression was measured by real-time reverse transcriptase-polymerase chain reaction and the endogenous expression and activating phosphorylation of ezrin protein analyzed by Western blot test. RESULTS: Ezrin overexpression was significantly associated with remarkable tumor necrosis (P = 0.025), increased histological grades (P = 0.037), advanced American Joint Committee on Cancer stages (P = 0.034), and higher mitotic rate (P < 0.001). Importantly, ezrin overexpression independently predicted inferior metastasis-free survival (P = 0.012, risk ratio = 4.083) and disease-specific survival (P = 0.0337, risk ratio = 4.537). The mRNA and total protein of ezrin in various cells were comparable in the expression level. Despite variation in abundance, phosphorylated ezrin at threonine(567) was detectable in myxofibrosarcoma cell lines but not in fibroblasts. CONCLUSIONS: In primary myxofibrosarcomas, ezrin overexpression correlates with important prognostic elements and independently portends worse outcomes, highlighting the potential prognostic usefulness of ezrin in predicting tumor aggressiveness. PMID- 20585870 TI - Positive peritoneal cytology in patients with gastric cancer: natural history and outcome of 291 patients. AB - BACKGROUND: Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort. METHODS: Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS). RESULTS: From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+ , DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt+ disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt+ patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003). CONCLUSIONS: Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt+ disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain. PMID- 20585871 TI - Histone deacetylase (HDAC) 1 and 2 expression and chemotherapy in gastric cancer. AB - BACKGROUND: Histone deacetylases (HDACs) modulate chromatin and may influence the effect of DNA-damaging drugs. We investigated HDAC1 and -2 expression in gastric carcinomas (GCs) for an association of patient outcome with conventional neoadjuvant chemotherapy. In vitro, HDAC inhibitors were evaluated as alternative treatment options. METHODS: HDAC1/2 expression was analyzed immunohistochemically in 127 pretherapeutic biopsy samples of neoadjuvant (platinum/5-fluorouracil) chemotherapy-treated GC patients and correlated with response and overall survival (OS). Chemosensitivity of four GC cell lines to cisplatin and the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and valproic acid was determined by XTT assays. Efficiencies of combined drug schedules were analyzed. RESULTS: High expression of HDAC1/2 was found in 69 (54%) of 127 and 108 (85%) of 127 carcinomas, respectively, and was not associated with response or OS. In patients whose disease responded to therapy, high HDAC1 expression was associated with worse OS (P = 0.005). In cell lines, sequential treatment with SAHA and cisplatin showed synergistic effects irrespective of the initial cisplatin sensitivity. CONCLUSIONS: HDAC1 and -2 expression is not suitable to predict response or survival for neoadjuvant-treated GC patients, but HDAC1 expression may be used for risk stratification in patients whose disease responds to therapy. Sequential treatment with SAHA and cisplatin may represent an alternative treatment option for GC patients. PMID- 20585872 TI - Health insurance status affects staging and influences treatment strategies in patients with hepatocellular carcinoma. AB - BACKGROUND: Lack of health insurance is associated with poorer outcomes for patients with cancers amenable to early detection. The effect of insurance status on hepatocellular carcinoma (HCC) presentation stage and treatment outcomes has not been examined. We examined the effect of health insurance status on stage of presentation, treatment strategies, and survival in patients with HCC. METHODS: The Tennessee Cancer Registry was queried for patients treated for HCC between January 2004 and December 2006. Patients were stratified by insurance status: (1) private insurance; (2) government insurance (non-Medicaid); (3) Medicaid; (4) uninsured. Logistic, Kaplan-Meier, and Cox models tested the effects of demographic and clinical covariates on the likelihood of having surgical or chemotherapeutic treatments and survival. RESULTS: We identified 680 patients (208 private, 356 government, 75 Medicaid, 41 uninsured). Uninsured patients were more likely to be men, African American, and reside in an urban area (all P < 0.05). The uninsured were more likely to present with stage IV disease (P = 0.005). After adjusting for demographics and tumor stage, Medicaid and uninsured patients were less likely to receive surgical treatment (both P < 0.01) but were just as likely to be treated with chemotherapy (P >= 0.243). Survival was significantly better in privately insured patients and in those treated with surgery or chemotherapy (all P < 0.01). Demographic adjusted risk of death was doubled in the uninsured (P = 0.005). CONCLUSIONS: Uninsured patients with HCC are more likely to present with late-stage disease. Although insurance status did not affect chemotherapy utilization, Medicaid and uninsured patients were less likely to receive surgical treatment. PMID- 20585873 TI - Predicting adverse outcomes after complex cancer surgery. PMID- 20585874 TI - Peritoneal sarcomatosis: is there a subset of patients who may benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy? AB - BACKGROUND: Unlike novel molecular-targeted therapies for metastatic gastrointestinal stromal tumors (GIST), conventional treatments for peritoneal sarcomatosis (PS) are mostly ineffective. As with carcinomatosis of epithelial origin, a rationale base supports an aggressive locoregional treatment of PS, but the use of CRS and HIPEC in this setting is still controversial. We assessed the outcome of clinically and pathologically homogeneous subsets of patients with PS uniformly treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A prospective database of 37 patients who underwent CRS and close-abdomen HIPEC with cisplatin and doxorubicin or mitomycin C was reviewed. PS originated from GIST (pre-imatinib era) in 8 patients, uterine leiomyosarcoma (ULS) in 11, retroperitoneal liposarcoma (RPLP) in 13, and other sarcoma in 5. RESULTS: CRS was macroscopically complete in 28 patients (75.7%). Operative mortality was 3.7% and morbidity 21.6%. After median follow-up of 104 (range, 1-131) months, peritoneal disease progression occurred in 16 patients, distant metastases in 5, and both in 13. For all patients, median overall survival was 26.2 months; 7 patients were alive at 46-130 months (ULS, n = 4; RPLP, n = 2; GIST, n = 1). RPLP had the best overall survival (median, 34 months) but 100% peritoneal relapse; GIST had dismal overall, local-regional-free and distant-free survival; ULS had the higher proportion of long survivors and best local-regional-free survival. CONCLUSIONS: Overall, results of CRS and HIPEC did not compare favorably to those of conventional therapy. In a subgroup analysis, the combined approach did not change GIST and RPLS natural history. The interesting results with ULS may warrant further investigations. PMID- 20585875 TI - Assessment of ACS NSQIP's predictive ability for adverse events after major cancer surgery. AB - BACKGROUND: The American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) has improved operative outcomes in the USA. However, its applicability to oncologic resections at ACS NSQIP hospitals has not been fully explored. We assessed the ability of factors currently collected by ACS NSQIP to predict adverse operative events after major cancer surgery. METHODS: Using pre- and intraoperative factors gathered by the 2005-2008 ACS NSQIP, we constructed logistic regression models to determine their ability to predict 30-day mortality, prolonged length of stay (LOS), major complications or increased number of complications in 15,709 patients who underwent major cancer surgery at 211 hospitals. We assessed each model's predictive ability using the c-index. RESULTS: While the mortality rate was relatively low (2.5%), nearly 24% of patients experienced major adverse events. However, up to 43% of patients with prolonged LOS did not have any major complication captured by NSQIP. Furthermore, our model predicting complications showed poor overall predictive ability compared with those predicting mortality and LOS (c-index <0.67 versus 0.80 and 0.73, respectively). When stratified by procedure, the complication model's predictive ability remained less accurate than models predicting 30-day mortality or prolonged LOS. These results remain unchanged after additional sensitivity analyses. CONCLUSIONS: Current ACS NSQIP variables show low predictive ability for major complications after major oncologic resections. Addition of some disease- and operation-specific variables may be an important consideration in the further evolution of the NSQIP to allow for more accurate predictions of adverse outcomes for major oncologic resections. PMID- 20585876 TI - Consequences of axillary ultrasound in patients with T2 or greater invasive breast cancers. AB - BACKGROUND: Axillary ultrasound (AUS) with needle biopsy is used to detect metastasis in patients with invasive breast cancers. Our hypothesis is that preoperative AUS significantly reduces sentinel node biopsy (SLNB) use in patients with invasive breast tumors >2 cm upon clinical examination. METHODS: A single-institution database of patients with breast cancer and AUS was reviewed. Patients with incomplete records, clinical tumor <2 cm, or postoperative AUS were excluded. A control cohort of non-AUS patients with clinical T2 (cT2) or greater disease was identified. Clinicopathologic data were collected. Simple Kappa coefficient and chi-square statistical analyses were performed. RESULTS: AUS was performed in 153 patients vs. 370 controls. Of AUS patients, 112 (73.2%) had cT2 disease vs. 272 (73.5%) controls. Median AUS patient age was 53.7 (range, 22.8 85.8) years vs. 53.8 (range, 26.7-91.6) years; median pathologic tumor was 3.8 (range, 1.0-20.0) cm in AUS patients vs. 2.5 (range, 0.1-11.0) cm. Among AUS patients, 78% had needle biopsy; 85 of 120 (70.8%) were positive. Sixty-eight patients had SLNB: 33 after negative AUS and 35 after negative needle biopsy. Twenty-three SLNB (37.3%) were positive; 15 of 33 after negative AUS and 8 of 35 after a negative needle biopsy. Axillary dissection was performed in 102 of 153 vs. 225 of 370 controls. Sensitivity and specificity of AUS was 86.2% and 40.5%. Sensitivity of AUS plus needle biopsy was 89.3% with 100% specificity. Neoadjuvant chemotherapy was given to 49.7% of AUS patients. AUS reduced costs by more than $4,000 per patient. CONCLUSIONS: AUS reduces SLNB use and affects treatment in patients with cT2 or greater breast cancer. Routine AUS should be considered in this population. PMID- 20585877 TI - Outcomes of pediatric patients with malignancies of the major salivary glands. AB - BACKGROUND: To report the outcomes and early to long term treatment complications among pediatric patients with major salivary gland malignancies treated at a single institution. MATERIALS AND METHOD: This study was a retrospective case review set at a tertiary referral cancer center. Patients less than 19 years of age with a diagnosis of a major salivary gland malignancy were identified at the M. D. Anderson tumor database between 1953 and 2006. RESULTS: A total of 61 patients were identified, with equal gender distribution. The majority of tumors arose in the parotid gland (83%), and the most common pathology was mucoepidermoid carcinoma (46%). Lymphatic metastasis was identified in 37% of patients, nearly all with mucoepidermoid carcinoma. Although 65% of patients had prior treatment elsewhere, more than 75% of patients underwent surgical resection at our institution. External beam radiation was used in 45% of patients, with an average dose of 58.6 Gray. Average patient follow-up was 153 months. The overall survival rate was 93% at 5 years, and 26% developed a recurrence. A second primary was identified in 2 patients. Permanent facial paresis was noted in 7 patients (12%) and xerostomia in 1 patient (4%). CONCLUSIONS: Survival of pediatric patients with major salivary gland carcinomas is favorable. Adverse outcomes were best predicted by tumor grade, margin status, and neural involvement. Radiation therapy is beneficial for locoregional control of disease, with acceptable long-term treatment sequelae, and without a significant risk for developing second primary tumors. Survivorship issues need to be addressed in this patient population into adulthood. PMID- 20585878 TI - Clinical outcomes and prognostic factors of metastatic gastric carcinoma patients who experience gastrointestinal perforation during palliative chemotherapy. AB - BACKGROUND: We conducted the current study to investigate the clinical outcomes of metastatic gastric carcinoma (MGC) patients who experienced gastrointestinal (GI) perforation during palliative chemotherapy and to examine the prognostic factors associated with survival after perforation. METHODS: We reviewed the medical records of patients at the Center for Gastric Cancer of the National Cancer Center, Korea who developed GI perforation during palliative chemotherapy between January 2001 and December 2008. RESULTS: Of the 1,856 patients who received palliative chemotherapy for MGC, 32 patients (1.7%) developed GI perforation during chemotherapy. Patients with perforation at the primary gastric site were more likely to have ulcerative gastric cancer lesion (90.5 vs. 40.0%, P = 0.034) or gastric tumor bleeding (28.6 vs. 0%, P = 0.298), and less likely to have Bormann type IV (14.3 vs. 60.0%, P = 0.062), than patients with perforation at nongastric sites. In 14 patients (43.8%) who resumed chemotherapy after perforation, the disease control rate was 57.1%, and median overall survival (OS) after perforation was 7.5 months [95% confidence interval (CI), 6.0-9.0 months]. In all patients, median OS following perforation was 4.0 months (95% CI, 1.5-6.6 months), and multivariate analysis revealed that differentiated tumor histology, response to chemotherapy before perforation, and absence of septic shock at time of perforation were significantly associated with favorable OS after perforation. CONCLUSIONS: As patients experiencing GI perforation during palliative chemotherapy have heterogeneous clinical presentation, we need to adopt different approaches in the management of the patients that are compatible with the favorable prognostic factors. PMID- 20585879 TI - Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. AB - BACKGROUND: Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients. METHODS: We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan Meier and Cox regression models. RESULTS: Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05). CONCLUSIONS: Liver-directed surgery for NELM is associated with prolonged survival; however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management. PMID- 20585880 TI - CpG methylation of transcription factor 4 in gastric carcinoma. AB - BACKGROUND: Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis. METHODS: The extent of methylation in the TCF4 promoter was assessed using methylation specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples. RESULTS: The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p < 0.05) GCs. There was a significant difference in TCF4 methylation between GCs and normal gastric mucosa (67.5 vs. 40.0%, respectively, by MSP and 75.8 vs. 30.0%, respectively, by PS; p < 0.05). There was significant correlation between TCF4 methylation status by PS and tumor size (p = 0.004), Lauren classification (p = 0.043), depth of invasion (p < 0.001), nodal metastasis (p = 0.021), and tumor node-metastasis (TNM) stage (p = 0.045). CONCLUSIONS: These results suggest that inactivation of TCF4 by promoter methylation may play a role in the early stage of gastric carcinoma progression. Furthermore, standard polymerase chain reaction followed by PS may provide a more specific and quantitative diagnostic alternative to MSP, which may be of benefit in oncology research. PMID- 20585881 TI - Simulation of the influence of industrial wastewater on a municipal sewage treatment plant--a case study. AB - PURPOSE: Industrial wastewater flow caused operational difficulties in the wastewater treatment plant in Debrecen, Hungary. Bioaugmentation was successfully applied to maintain effluent quality in the periods when wastewater of high starch content was accepted, but, at the end of 2008, the nitrification capacity of the plant decreased considerably due to improperly pre-treated pharmaceutical wastewater. METHODS AND MATERIAL: Dynamic simulations were carried out in a prototype programme developed by the Environmental Expert System Research Group at the University of Pannonia, Hungary. Several parameters for heterotrophic biomass were adjusted in function of time, and the specific growth rate of autotrophic biomass was altered in function of time and temperature in order to describe the effects of inoculation and toxic influence. Simulations were carried out with both constant and adjusted parameters. RESULTS: Though results on effluent COD of the different modelling versions were similar, the ammonia concentration fitted the measured data only when modified parameters were used. The study revealed that the autotrophic biomass had slowly adapted to the toxic compound. Different control strategies of aeration and decreased excess sludge removal rate were tested to enhance the nitrification in the critical time intervals. The amount of ammonia and inorganic nitrogen decreased in all cases while the oxygen demand increased to a maximum of 10.1%. CONCLUSIONS: Reducing excess sludge removal rate gave satisfactory results even without changing aeration. Further improvement could be achieved by introducing aeration into the post-denitrification reactor. The combination of the two modifications can compensate for the effect caused by toxicity. PMID- 20585883 TI - Is public housing the cause of poor health or a safety net for the unhealthy poor? AB - Research has shown that public housing residents have the worst health of any population in the USA. However, it is unclear what the cause of that poor health is among this population. The purpose of this paper is to investigate the association between public housing and health conditions: specifically, we ask if residents entered public housing already ill or if public housing may cause the poor health of its residents. The data used for this study come from the GSU Urban Health Initiative, which is a prospective, mixed-methods study of seven public housing communities earmarked for demolition and relocation (N = 385). We used the pre-relocation, baseline survey. We found that, while health was not the main reason residents gave for entering public housing, the majority of public housing residents entered public housing already ill. Substandard housing conditions, long tenure in public housing, and having had a worse living situation prior to public housing were not associated with an increased risk of a health condition diagnosed after entry into public housing. Our findings suggest that public housing may have provided a safety net for the very unhealthy poor. PMID- 20585884 TI - Nucleotide sequence and variations of the bovine myocyte enhancer factor 2C (MEF2C) gene promoter in Bos taurus cattle. AB - Myocyte Enhancer Factor 2 (MEF2) proteins are a small family of transcription factors that play pivotal role in morphogenesis and myogenesis of skeletal, cardiac, and smooth muscle cells. In vertebrates, there are four MEF2 genes, referred to as MEF2A, -B, -C, and -D, that are located on different chromosomes. After birth MEF2A, MEF2B, MEF2D transcriptions are expressed ubiquitously, whereas MEF2C transcripts are restricted to skeletal muscle, brain, and spleen. In this study, on the basis of the sequences of the bovine chromosome 7 genomic contig, available in the GenBank database, sets of PCR primers were designed and to amplify the bovine MEF2C gene promoter region, exon 1 (5'UTR) and part sequence of the intron 1. Seven overlapping fragments of the bovine MEF2C gene were amplified and then sequenced. Altogether, these fragments were composed in the 3,120-bp sequence which was deposited in the GenBank database under accession no. GU211007. The sequence fragment included the putative site of the promoter region and transcription start of the exon 1. The sequence analysis of these fragments in individual animals representing different Bos taurus breeds revealed four variations in promoter region: g.-1606C>T, g.-1336_-1335DelG, g.-818C>T, g. 613_-612DelA and four SNPs within intron 1: g.2711A>G, g. 2913A>G, g.2962G>T and g.3014A>G. No polymorphism was found within sequence of the exon 1 (5'UTR). These polymorphisms were identified for first time using these sequences and were confirmed by RFLP or MSSCP methods. PMID- 20585885 TI - Immunohistochemical distribution of the tetraspanin CD9 in normal porcine tissues. AB - The tetra-membrane-spanning protein, CD9 is a 24-27 kDa cell surface glycoprotein expressed in a wide variety of human cells being involved in a variety of cell processes, including signaling, adhesion, motility, fertilization and tumor cells metastasis. By means of a polyclonal antibody (N1) raised against recombinant swine CD9 protein, we studied the immunohistochemical expression of CD9 on different normal swine tissues. Immunochemistry shows that swine CD9 was distribute in a similar form than in human tissues, being present on epithelial cells of lung, liver, kidney, skin, tonsil, testis (epididymo), gut mucosa, uterus and mama. Furthermore, polyclonal antibody against swine CD9 reacts with white matter from cerebrum and cerebellum, peripheral nerves fibers and Hassal corpuscle from thymus and ovum. Platelets react strongly with our antibody, but monocytes and neutrophils react lightly. These results suggest that CD9 antigen should play a similar functional role in swine and human and therefore studies on CD9 on swine as an animal model would allow new knowledge about its role in adhesion, fertilization and tumor metastasis among other important biomedical processes. PMID- 20585886 TI - Novel SNPs of the bovine CACNA2D1 gene and their association with carcass and meat quality traits. AB - Calcium channel, voltage-dependent, alpha-2/delta subunit 1 (CACNA2D1) gene encodes a member of the alpha-2/delta subunit family, proteins are accessory molecules associated with voltage-gated calcium channels, and increase the density at the plasma membrane of calcium channels activated by high voltage. The main objective of the present study was to identify polymorphisms of CACNA2D1 gene, and to analyze associations between these polymorphisms and carcass and meat quality traits in cattle. In this study, through PCR-SSCP and DNA sequencing methods, two new allelic variant corresponding to the C->G and G->T mutations at positions 526740 and 537917 in the exon25 and exon35 of bovine CACNA2D1 gene, respectively, could be detected. SNP C526740G is a nonsynonymous mutation, resulting in a Cysteine (Cys) to Tryptophan (Trp) amino acid replacement and SNP G537917T resulting in an Aspartic (Asp) to Tyrosine (Tyr) amino acid replacement. The gene-specific SNP markers association analysis was investigated. The C526740G was significantly associated with Meat color (MC) (P=0.0297) and Backfat thickness (BF) (P<0.001). The G537917A indicated significant association with Dressing percentage (DP) (P=0.0485). No significant association, however, was detected between any of the marker genotype and other traits measured in this study. Results from this study initially suggested that CACNA2D1 gene is one of the potential candidate genes influencing carcass and meat quality traits and gene-specific SNPs may be a useful marker for MAS programs in cattle breeding. PMID- 20585887 TI - The proliferation and differentiation of osteoblasts in co-culture with human umbilical vein endothelial cells: An improved analysis using fluorescence activated cell sorting. AB - The interaction of osteoblasts and endothelial cells plays a pivotal role in osteogenesis. This interaction has been extensively studied using their direct co culture in vitro. However, co-culture experiments require clear discrimination between the two different cell types in the mixture, but this was rarely achieved. This study is the first to use fluorescence-activated cell sorting (FACS) for the separation and quantitative analysis of the proliferation and differentiation of MG-63 cells grown in direct co-culture with human umbilical vein endothelial cells (HUVECs). The cells of the MG-63 cell line have properties consistent with the characteristics of normal osteoblasts. We labeled HUVECs with fluorescent antibody against CD31 and used FACS to measure the proportions of each cell type and to separate them based on their different fluorescence intensities. The rate of proliferation of the MG-63 cells was estimated based on a count of the total viable cells and the proportion of MG-63 cells in the mixture. The mRNA expression levels of the osteoblast differentiation markers alkaline phosphatase (ALP), collagen type 1 (Coll-1) and osteocalcin (OC) in the MG-63 cells were measured via real-time PCR after the separation via FACS. We found that HUVECs stimulated the proliferation of the MG-63 cells after 72 h of co-culture, and inhibited it after 120 h of co-culture. The mRNA expression levels of ALP and Coll-1 significantly increased, whereas that of OC significantly decreased in MG-63 after co-culture with HUVECs. Using FACS for the quantitative analysis of the proliferation and differentiation of osteoblasts directly interacting with endothelial cells could have merit for further co culture research. PMID- 20585888 TI - ZNF300, a recently identified human transcription factor, activates the human IL 2Rbeta promoter through the overlapping ZNF300/EGR1 binding site. AB - ZNF300 was recently identified as a member of the human KRAB/C(2)H(2) zinc finger protein family. Little is known about the role of ZNF300 in human gene regulation networks. In this study, the DNA-binding property of ZNF300 was further analyzed. We found that the recombinant ZNF300 could bind to the binding site 5'-GCGGGGGCG 3' of Egr1, another member of the KRAB/C(2)H(2) zinc finger protein family. Similarly, recombinant Egr1 also showed a similar binding affinity to the ZNF300 binding site 5'-CTGGGGGCG-3'. Bioinformatics analysis revealed that there is an overlapping ZNF300/Egr1 binding site in the human IL-2Rbeta promoter region, which was previously known to be recognized by endogenous Egr1. Electrophoretic mobility shift assays showed that endogenous ZNF300 could also bind to this site. A transient transfection assay revealed that both ZNF300 and Egr1 could transactivate the IL-2Rbeta promoter, and that the activation was abrogated by a mutation of residues in the overlapping ZNF300/Egr1 binding site. Co-expression of ZNF300 and Egr1 led to enhanced IL-2Rbeta promoter activity. Thus, ZNF300 is likely to be another regulator of the human IL-2Rbeta promoter. PMID- 20585889 TI - R proteins as fundamentals of plant innate immunity. AB - Plants are attacked by a wide spectrum of pathogens, being the targets of viruses, bacteria, fungi, protozoa, nematodes and insects. Over the course of their evolution, plants have developed numerous defense mechanisms including the chemical and physical barriers that are constitutive elements of plant cell responses locally and/or systemically. However, the modern approach in plant sciences focuses on the evolution and role of plant protein receptors corresponding to specific pathogen effectors. The recognition of an invader's molecules could be in most cases a prerequisite sine qua non for plant survival. Although the predicted three-dimensional structure of plant resistance proteins (R) is based on research on their animal homologs, advanced technologies in molecular biology and bioinformatics tools enable the investigation or prediction of interaction mechanisms for specific receptors with pathogen effectors. Most of the identified R proteins belong to the NBS-LRR family. The presence of other domains (including the TIR domain) apart from NBS and LRR is fundamental for the classification of R proteins into subclasses. Recently discovered additional domains (e.g. WRKY) of R proteins allowed the examination of their localization in plant cells and the role they play in signal transduction during the plant resistance response to biotic stress factors. This review focuses on the current state of knowledge about the NBS-LRR family of plant R proteins: their structure, function and evolution, and the role they play in plant innate immunity. PMID- 20585890 TI - The selection of aptamers specific for membrane molecular targets. AB - A growing number of RNA aptamers have been selected experimentally using the SELEX combinatorial approach, and these aptamers have several advantages over monoclonal protein antibodies or peptides with respect to their applications in medicine and nanobiotechnology. Relatively few successful selections have been reported for membrane molecular targets, in contrast to the situation with non membrane molecular targets. This review compares the procedures and techniques used in selections against membrane proteins and membrane lipids. In the case of membrane proteins, the selections were performed against soluble protein fragments, detergent-membrane protein mixed micelles, whole cells, vesicles derived from cellular membranes, and enveloped viruses. Liposomes were used as an experimental system for the selection of aptamers against membrane lipids. RNA structure-dependent aptamer binding for rafts in lipid vesicles was reported. Based on the selected aptamers against DOPC and the amino acid tryptophan, a specific passive membrane transporter composed of RNA was constructed. The determination of the selectivity of aptamers appears to be a crucial step in a selection, but has rarely been fully investigated. The selections, which use whole cells or vesicles derived from membranes, can yield aptamers not only against proteins but also against membrane lipids. PMID- 20585891 TI - Anti-scratching behavioral effects of N-stearoyl-phytosphingosine and 4 hydroxysphinganine in mice. AB - N-Stearoyl-phytosphingosine (SPS) and 4-hydroxysphinganine (phytosphingosine, PS), which are sphingolipids frequently found in mammalian skin, plants, and yeast, have been used as ingredients in cosmetics. In mice, treatment with SPS and PS inhibited histamine-induced scratching behavior and vascular permeability. These agents inhibited the expression of the allergic cytokines, IL-4 and TNF alpha, and the activation of the transcription factors, NF-kappaB and c-jun, in histamine-stimulated skin tissues. These agents also showed potent anti-histamine effects in the Magnus test using guinea pig ileum. Based on these results, SPS and PS may improve scratching behavioral reactions in skin by regulating the action of histamine and the activation of the transcription factors NF-kappaB and c-jun. PMID- 20585892 TI - Developing and communicating responsible data management policies to trainees and colleagues. AB - The basic components of data management including data ownership, collection, selection, recording, analysis, storage, retention, destruction, and sharing. A number of important principles underlie best practices for each of these components; these include recording details such that another can repeat the experiment, keeping the data safe, managing storage in such a way as to facilitate easy retrieval for the period of time required by regulatory agencies and establishing data sharing principles with colleagues before collaborations begin. Experience as practicing scientists and teachers has aided in developing helpful strategies and approaches for communicating these principles, policies and practices to trainees and colleagues. We recommend didactic instruction focused by discipline, combined with the use of "teachable moments" in a student's career, as well as teaching principles versus rules, because changing methods of data collection and storage have implications for data management practices. PMID- 20585893 TI - Effect of PP-2A on neurite outgrowth in neuronal cells. AB - Protein phosphatase 2A (PP-2A) has been implicated to be crucial in neural development and the normal function of nervous system. However, little is known about its role in neuritogenesis. In this study, we reported that inhibition of PP-2A strongly suppresses the outgrowth of cell processes only during the initiation stage, while activation of PP-2A promotes extensive outgrowth of long neurites in Neura2A cells and long single axon or multiple axons in hippocampal neurons. Our results indicated that PP-2A may be an important positive regulator in neurite outgrowth, and upregulation PP-2A could be a possible target for the therapy of axonopathy in neural diseases. PMID- 20585894 TI - Primary culture and characteristic morphologies of neurons from the cerebral ganglion of the mud crab, Scylla paramamosain. AB - Crustacean neurons, obtained from the cerebral ganglion of the mud crab Scylla paramamosain, were successfully cultured in vitro. They maintained typical morphological characteristics and showed better outgrowth in modified Medium 199 (M199) medium than that in Liebowitz's L-15 medium. Fetal bovine serum (FBS), muscle extracts, and hemolymph of the mud crab S. paramamosain were added as supplements. Only 20% FBS could promote neuron outgrowth, while muscle extracts and hemolymph of S. paramamosain did not improve neuron outgrowth. For cell dissociation, both collagenase type I and trypsin worked well as determined by initial cell viability and following cell outgrowth potential. More than six kinds of cells with different morphological characteristics were identified in the neuron outgrowth. They were "small cells", "veilers", "branchers", "multipolar cells", "super-large cell", and "bipolar cells". Among all of the cells, bipolar cells were identified for the first time in crustacean neurons culture and they could live longer than other cells. The neurons could grow for more than a week before retraction and eventual degradation. PMID- 20585896 TI - Irish mothers' intentions to have daughters receive the HPV vaccine. AB - BACKGROUND: Most cases of cervical cancer are associated with human papillomavirus (HPV) types 16 and 18. This study examined the effect of message framing on mother's intentions to obtain HPV vaccination for their teenage daughters and investigated predictors of HPV vaccination intentions. METHODS: Seventy-two mothers of daughters in the 8-16-year age group were randomly assigned to read either a gain-framed (describing the benefits of receiving the vaccine) or a loss-framed (describing the costs of not receiving the vaccine) message and completed measures assessing their intention to have their daughter/s vaccinated, normative beliefs, attitudes and perceived behavioural control. CONCLUSIONS: Awareness of HPV was low but intentions to vaccinate were high. There was no effect of message frame on vaccination intentions. Attitudes towards HPV vaccination and the influence of both peers and medical professionals are important factors in HPV vaccine acceptability. PMID- 20585895 TI - Matrix compositions and the development of breast acini and ducts in 3D cultures. AB - Breast epithelial cells develop into polarized and highly organized acinar and ductal structures in response to stromal cues, including extracellular matrix composition and density, which can in part be reproduced in 3D culture conditions. Here, we present the effects of various 3D in vitro stroma compositions (termed "matrices" or "substrates") on the ability of heterotypic cultures of epithelial and mesenchymal stem cells to organize into acinar and tubular structures. Normal murine mammary gland (NMuMG) cells were cultured, either alone or in combination (30:70) with mouse mesenchymal stem cells (D1), in 3D matrices generated by agarose, collagen, and Matrigel alone or by a combination thereof. After 3-5 d in culture, cell distribution, organization, and the presence of acinus-like and tubule-like structures were determined. The number of acinar structures was significantly higher in cultures grown in combination matrices of agarose with Matrigel or collagen I when compared with cultures grown in Matrigel or collagen I alone (p < 0.05). No tubular structures were formed when agarose was included in the matrix, regardless of the combination. In Matrigel, but not in collagen I/Matrigel microenvironment, the number of tubular structures was significantly increased in NMuMG/D1 coculture when compared with culture of NMuMG cells alone (p < 0.05). By immunohistochemical analysis, NMuMG cells cocultured with D1 cells were shown to form acinar structures with the NMuMG epithelial cells surrounding a lumen composed of dead cells while the D1 cells were mostly peripheral. Immunostaining for laminin indicated the presence of basement membrane when NMuMG cells were grown in Matrigel alone or cocultured with D1 cells in a combination of Matrigel and collagen I. These results indicate that the physical and biochemical properties of the matrix and cellular composition alter the organization of the mammary gland. PMID- 20585897 TI - Enhancing clostridial acetone-butanol-ethanol (ABE) production and improving fuel properties of ABE-enriched biodiesel by extractive fermentation with biodiesel. AB - The extractive acetone-butanol-ethanol (ABE) fermentations of Clostridium acetobutylicum were evaluated using biodiesel as the in situ extractant. The biodiesel preferentially extracted butanol, minimized product inhibition, and increased production of butanol (from 11.6 to 16.5 g L-1) and total solvents (from 20.0 to 29.9 g L-1) by 42% and 50%, respectively. The fuel properties of the ABE-enriched biodiesel obtained from the extractive fermentations were analyzed. The key quality indicators of diesel fuel, such as the cetane number (increased from 48 to 54) and the cold filter plugging point (decreased from 5.8 to 0.2 degrees C), were significantly improved for the ABE-enriched biodiesel. Thus, the application of biodiesel as the extractant for ABE fermentation would increase ABE production, bypass the energy intensive butanol recovery process, and result in an ABE-enriched biodiesel with improved fuel properties. PMID- 20585898 TI - Development of PACAP38 analogue with improved stability: physicochemical and in vitro/in vivo pharmacological characterization. AB - Pituitary adenylate cyclase activating polypeptide 38 (PACAP38), one of the major peptide transmitters, has emerged as a promising drug candidate for the treatment of type 2 diabetes. In the present study, on the basis of previous structure activity relationships, a new PACAP38 derivative, [R(15, 20, 21), L(17)]-PACAP38, was chemically synthesized with the aim of enhancing the therapeutic potential of PACAP38. The solution structure of the new derivative was almost identical to that of PACAP38 as evaluated by circular dichroic spectroscopy, and both PACAP38 and the new derivative stimulated adenylate cyclase in rat insulinoma RIN-m5F cells with EC(50) values of 4.6 and 5.5 nM, respectively. Stability studies revealed the gradual degradation of PACAPs in rat serum, although there appeared to be a 42% reduction in degradation kinetics for [R(15, 20, 21), L(17)]-PACAP38 compared with that of PACAP38. The novel derivative also exhibited more potent protective effects against streptozotocin (STZ)-induced apoptotic death of RIN m5F cells, possibly due to the enhanced stability. The n0-STZ model, in which neonatal rats were injected with STZ at birth, developed a typical diabetic condition; however, chronic administration of [R(15, 20, 21), L(17)]-PACAP38 resulted in protection of pancreatic islets, followed by the improvement of glycemic control. Thus, the chemical modification of PACAP38 led to the development of a new promising derivative with enhanced stability and biological activity, and early administration of [R(15, 20, 21), L(17)]-PACAP38 might be of help for preventing the development of diabetes in type 2 diabetic model rats. PMID- 20585899 TI - Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure. AB - Glaucoma is a neurodegenerative disease in which increasing intraocular pressure leads to the progressive loss of retinal ganglion cells (RGCs) and blindness. Here, we report a neuroprotective effect of pituitary adenylate cyclase activating polypeptide (PACAP) against RGC loss induced by high intraocular pressure in the rat. Vehicle or PACAP (1 fM to 1,000 pM) solution was injected into the vitreous body once after induction of a high intraocular pressure (110 mmHg). Seven days later, the number of viable RGCs was reduced to 45% of that in the intact control. However, PACAP treatment significantly reduced this RGC death in a bimodal manner, with peaks at 10 fM and 10-100 pM. The cAMP antagonist Rp cAMP significantly blocked the neuroprotective effect of PACAP at both high and low doses, whereas the MAP kinase inhibitor PD-98059 only prevented the effect of the low dose of PACAP. These findings suggest that PACAP has bimodal effects in the neuroprotection of RGCs against ischemia and that these effects are mediated via different signaling pathways. PMID- 20585900 TI - Oriented Markov random field based dendritic spine segmentation for fluorescence microscopy images. AB - Dendritic spines have been shown to be closely related to various functional properties of the neuron. Usually dendritic spines are manually labeled to analyze their morphological changes, which is very time-consuming and susceptible to operator bias, even with the assistance of computers. To deal with these issues, several methods have been recently proposed to automatically detect and measure the dendritic spines with little human interaction. However, problems such as degraded detection performance for images with larger pixel size (e.g. 0.125 MUm/pixel instead of 0.08 MUm/pixel) still exist in these methods. Moreover, the shapes of detected spines are also distorted. For example, the "necks" of some spines are missed. Here we present an oriented Markov random field (OMRF) based algorithm which improves spine detection as well as their geometric characterization. We begin with the identification of a region of interest (ROI) containing all the dendrites and spines to be analyzed. For this purpose, we introduce an adaptive procedure for identifying the image background. Next, the OMRF model is discussed within a statistical framework and the segmentation is solved as a maximum a posteriori estimation (MAP) problem, whose optimal solution is found by a knowledge-guided iterative conditional mode (KICM) algorithm. Compared with the existing algorithms, the proposed algorithm not only provides a more accurate representation of the spine shape, but also improves the detection performance by more than 50% with regard to reducing both the misses and false detection. PMID- 20585901 TI - Comparison of transfection efficiency of nonviral gene transfer reagents. AB - This study compared six commercially available reagents (Arrest-In, ExpressFect, FuGENE HD, jetPEI, Lipofectamine 2000, and SuperFect) for gene transfection. We examined the efficiency and cytotoxicity using nine different cell lines (MC3T3 E1 mouse preosteoblasts, PT-30 human epithelial precancer cells, C3H10T1/2 mouse stem cells, MCF-7 human breast cancer cells, HeLa human cervical cancer, C2C12 mouse myoblasts, Hep G2 human hepatocellular carcinoma, 4T1 mouse mammary carcinoma, and HCT116 human colorectal carcinoma), and primary cells (HEKn human epidermal keratinocytes) with two different plasmid DNAs encoding luciferase or beta-galactosidase in the presence or absence of serum. Maximal transfection efficiency in MC3T3-E1, C3H10T1/2, HeLa, C2C12, Hep G2, and HCT116 was seen using FuGENE HD, in PT-30, 4T1, and HEKn was seen using Arrest-In, and in MCF-7 was seen using jetPEI. Determination of cytotoxicity showed that the largest amount of viable cells was found after transfection with jetPEI and ExpressFect. These results suggest that FuGENE HD is the most preferred transfection reagent for many cell lines, followed by Arrest-In and jetPEI. These results may be useful for improving nonviral gene and cell therapy applications. PMID- 20585902 TI - Copy-number increase of AURKA in gastric cancers in a Chinese population: a correlation with tumor progression. AB - The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora targeted therapies. PMID- 20585903 TI - Woman's best friend? PMID- 20585904 TI - Exposure to indoor fungi: a new paradigm. PMID- 20585905 TI - There's a mouse in the house. PMID- 20585906 TI - Urodynamics in the evaluation of overactive bladder. AB - Overactive bladder (OAB) is a clinical syndrome characterized by urinary urgency, frequency, and nocturia with or without accompanying urinary incontinence. Thus, using this operational definition based on symptoms at presentation, urodynamic testing is not required for an initial diagnosis of OAB. An increasing body of evidence suggests that, although there is a relationship between the urodynamic finding of detrusor overactivity and OAB, these are quite separate findings, and successful response to nonsurgical and surgical interventions for OAB does not depend on finding detrusor overactivity on urodynamic testing. The role of urodynamics in the setting of OAB is not well defined at present, but there are several clinical scenarios where such testing may be useful. However, at this time, the evidence to support their routine use in patients with OAB is limited. PMID- 20585907 TI - Literature as a meaningful life laboratory. AB - Meaningful life is emotionally marked off. That's the general point that Johansen (IPBS: Integrative Psychological & Behavioral Science 44, 2010) makes which is of great importance. Fictional abstractions use to make the point even more salient. As an example I've examined Borges' famous fiction story. Along with the examples of Johansen it provides an informative case of exploring symbolic mechanisms which bind meaning with emotions. This particular mode of analysis draws forth poetry and literature in general to be treated as a "meaningful life laboratory". Ways of explanation of emotional effect the art exercises on people, which had been disclosed within this laboratory, however, constitute a significant distinction in terms that I have designated as "referential" and "substantive". The former appeals to something that has already been charged with emotional power, whereas the latter comes to effect by means of special symbolic mechanisms creating the emotional experience within the situation. Johansen, who tends to explain emotions exerted by the art without leaving the semiotic perspective, is drawn towards the "referential" type of explanation. Based upon discussions in theory of metaphor and Robert Witkin's sociological theory of arts it is demonstrated an insufficient of "referential" explanation. To overcome a monopoly of "referential" explanation of emotional engagement, in particular, in literature, means to break away from the way of reasoning, stating endless references to "something else", presupposing the existence of something already significant and therefore sharing its effects. PMID- 20585908 TI - Simple chromatographic method for simultaneous analyses of phosphatidylcholine, lysophosphatidylcholine, and free fatty acids. AB - This study describes a simple chromatographic method for the simultaneous analyses of phosphatidylcholine (PC) and its hydrolytic degradation products: lysophosphatidylcholine (LPC) and free fatty acids (FFA). Quantitative determination of PC, LPC, and FFA is essential in order to assure safety and to accurately assess the shelf life of phospholipid-containing products. A single run normal-phase high-performance liquid chromatography (HPLC) with evaporative light scattering detector has been developed. The method utilizes an Allsphere silica analytical column and a gradient elution with mobile phases consisting of chloroform: chloroform-methanol (70:30%, v/v) and chloroform-methanol-water ammonia (45:45:9.5:0.5%, v/v/v/v). The method adequately resolves PC, LPC, and FFA within a run time of 25 min. The quantitative analysis of PC and LPC has been achieved with external standard method. The free fatty acids were analyzed as a group using linoleic acid as representative standard. Linear calibration curves were obtained for PC (1.64-16.3 MUg, r(2) = 0.9991) and LPC (0.6-5.0 MUg, r(2) = 0.9966), while a logarithmic calibration curve was obtained for linoleic acid (1.1-5.8 MUg, r(2) = 0.9967). The detection and quantification limits of LPC and FFA were 0.04 and 0.1 MUg, respectively. As a means of validating the applicability of the assay to pharmaceutical products, PC liposome was subjected to alkaline hydrolytic degradation. Quantitative HPLC analysis showed that 97% of the total mass balance for PC could be accounted for in liposome formulation. The overall results show that the HPLC method could be a useful tool for chromatographic analysis, stability studies, and formulation characterization of phospholipid-based pharmaceuticals. PMID- 20585909 TI - Does alignment in the hindfoot radiograph influence dynamic foot-floor pressures in ankle and tibiotalocalcaneal fusion? AB - BACKGROUND: The Saltzman-el-Khoury hindfoot alignment view (HAV) is considered the gold standard for assessing the axis from hindfoot to tibia. However, it is unclear whether radiographic alignment influences dynamic load distribution during gait. QUESTIONS/PURPOSES: We evaluated varus-valgus alignment by the HAV and its influence on dynamic load distribution in ankle and tibiotalocalcaneal (TTC) arthrodesis. PATIENTS AND METHODS: We clinically assessed 98 patients (ankle, 56; TTC, 42) with SF-36 and American Orthopaedic Foot and Ankle Society (AOFAS) scores, visual hindfoot alignment, HAV angle, and dynamic pedobarography using a five-step method. For comparison, 70 normal feet were evaluated. Minimum followup was 2 years (average, 4.11 years; range, 2-6 years). RESULTS: The mean HAV angle was -0.8 degrees +/- 7.8 degrees for ankle and -1.2 degrees +/- 6.9 degrees for TTC arthrodesis. The HAV angle correlated with pedobarographic load distribution (r = 0.35-0.53). Radiographic alignment did not influence SF-36 or AOFAS scores; however, load distribution correlated to qualities of these scores. Visual alignment only predicted the corresponding HAV angle in 48%. To reproduce the dynamic load of healthy subjects, HAV angles of 5 degrees to 10 degrees valgus were needed. CONCLUSIONS: Visual positioning is inadequate to determine intraoperative positioning and resulted in a varus position with a relatively large SD. The HAV should be used to assess the hindfoot alignment correctly. HAV angles of 5 degrees to 10 degrees valgus are needed to reproduce a physiologic gait pattern. PMID- 20585910 TI - Orthopaedic case of the month: ankle pain and swelling in a 23-year-old man. PMID- 20585911 TI - Shed blood-derived cells from total hip arthroplasty have osteoinductive potential: a pilot study. AB - BACKGROUND: Cell therapy using autologous cells has been used in the treatment of various medical conditions. The mononuclear cell (MNC) fraction of bone marrow (BM) contains stem/progenitor cells that could contribute to osteogenesis and angiogenesis. QUESTIONS/PURPOSES: We asked whether MNCs derived from intraoperative shed blood (SB), consisting of peripheral blood and BM, have osteoinductive and angiogenic potential. METHODS: We harvested SB and BM from six patients undergoing THA. Isolated MNCs from SB and BM were analyzed by flow cytometry to evaluate the CD34(+) cell fraction and 1 * 10(6) cells were seeded on an interconnective porous calcium hydroxyapatite ceramic (IP-CHA) and transplanted in the backs of athymic rats. IP-CHAs without cells were transplanted as controls and all composites were harvested after 4 and 8 weeks. Osteoinductive potential was evaluated by histologic observation, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) using anti osteocalcin (OC) antibodies qualitatively and quantitatively. To evaluate angiogenic potential, capillary density was measured by immunohistochemistry using Isolectin B4 4 weeks after implantation. RESULTS: We found that CD34(+) cells existed in SB-MNCs and there was a trend toward lower frequency compared with BM-MNCs. Histologic osteoinduction, OC expression, and capillary density were increased by transplantation of MNCs from SB. Similar results were achieved with MNCs from BM. CONCLUSIONS: MNCs from SB have equivalent osteoinductive and angiogenic potential compared with those from BM. CLINICAL RELEVANCE: SB could be an attractive source for isolation of MNCs, enhancing osteoinduction and neovascularization, to augment the reconstruction of skeletal defects. PMID- 20585913 TI - Statistics in brief: Statistical power: what is it and when should it be used? PMID- 20585912 TI - Case reports: Painful limbs/moving extremities: report of two cases. AB - BACKGROUND: Painful limbs/moving extremities is a relatively rare condition characterized by aching pain in one limb and involuntary movement in the affected fingers or toes. Its pathomechanism is unknown. We report two patients with painful limbs/moving extremities. In one patient with a painful arm and moving fingers, the symptoms were resolved after surgery. CASE DESCRIPTIONS: Patient 1 was a 36-year-old man with a painful arm and moving fingers. Treatment with administration of analgesics was not effective. Postmyelographic CT showed stenosis of the right C5/C6 foramen attributable to cervical spondylosis and a defect of the contrast material at the foramen. He was treated with cervical foraminotomy. Patient 2 was a 26-year-old woman with a painful leg and moving toes. The pain and involuntary movement appeared 2 weeks after discectomy at L5/S1. Lumbar MRI and myelography showed no indications of nerve root compression. She was treated with a lumbar nerve root block. The pain and involuntary movement completely disappeared in both patients after treatment. LITERATURE REVIEW: Numerous studies report treatments for painful limbs/moving extremities, but few report successful treatment. Recently, botulinum toxin A injection and epidural spinal cord stimulation have been used and are thought to benefit this condition. Successful surgical treatment previously was reported for only one patient. PURPOSES AND CLINICAL RELEVANCE: If imaging indicates compression of nerve tissue, we believe surgical decompression should be considered for patients with painful limbs/moving extremities who do not respond to nonoperative treatment. PMID- 20585914 TI - The Mark Coventry Award: diagnosis of early postoperative TKA infection using synovial fluid analysis. AB - BACKGROUND: Synovial fluid white blood cell count is useful for diagnosing periprosthetic infections but the utility of this test in the early postoperative period remains unknown as hemarthrosis and postoperative inflammation may render standard cutoff values inaccurate. QUESTIONS/PURPOSES: We evaluated the diagnostic performance of four common laboratory tests, the synovial white blood cell count, differential, C-reactive protein, and erythrocyte sedimentation rate to detect infection in the first 6 weeks after primary TKA. METHODS: We reviewed 11,964 primary TKAs and identified 146 that had a knee aspiration within 6 weeks of surgery. Infection was diagnosed in 19 of the 146 knees by positive cultures or gross purulence. We compared demographic information, time from surgery, and the laboratory test values between infected and noninfected knees to determine if any could identify infection early postoperatively. Receiver operating characteristic curves were constructed to determine optimal cutoff values for each of the test parameters. RESULTS: Synovial white blood cell count (92,600 versus 4200 cells/MUL), percentage of polymorphonuclear cells (89.6% versus 76.9%), and C-reactive protein (171 versus 88 mg/L) were higher in the infected group. The optimal synovial white blood cell cutoff was 27,800 cells/MUL (sensitivity, 84%; specificity, 99%; positive predictive value, 94%; negative predictive value, 98%) for diagnosing infection. The optimal cutoff for the differential was 89% polymorphonuclear cells and for C-reactive protein 95 mg/L. CONCLUSIONS: With a cutoff of 27,800 cells/MUL, synovial white blood cell count predicted infection within 6 weeks after primary TKA with a positive predicted value of 94% and a negative predictive value of 98%. The use of standard cutoff values for this parameter (~ 3000 cells/MUL) would have led to unnecessary reoperations. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 20585915 TI - Pediatric cardiovascular device registries--the need for such data and the potential impact. PMID- 20585916 TI - Assessment of coronary blood flow with computed tomography and magnetic resonance imaging. PMID- 20585918 TI - The international arena of medical physics: where is Australasia? PMID- 20585917 TI - The enigma of Helicobacter pylori infection and gastric cancer. AB - Although H. pylori has been recognized as a class I carcinogen, incongruence between infection prevalence and cancer incidence has been reported. Holcombe called attention to the high prevalence of infection in the face of low cancer rates, which he called "The African Enigma". Similar observations have now been made in other geographic areas. Gastric carcinoma should be considered an infectious disease, for which the classical epidemiologic model of causality applies. The model proposes that tissue injury inflicted by the infectious agent is modulated by its interactions with host and environmental factors. Although approximately half of the world's population is infected, only a small proportion of people develop cancer. The African enigma is a striking example of the major contrasts in cancer risk among populations with similarly high prevalence of infection. The mechanisms involved in reducing the risk of cancer in infected individuals are explored in this article, which may lead to the design of effective prevention strategies. PMID- 20585919 TI - Manubriosternal joint: imaging features of normal anatomy and arthritis. AB - Normal findings of the manubriosternal joint vary and include narrowing, irregularity, and ankylosis. Proliferative changes are common during the degenerative process, and they include osteophyte formation and sclerosis. Ankylosis may be an end result. Imaging features of inflammatory arthritides are also generally nonspecific. Bone marrow and adjacent soft tissue change on magnetic resonance imaging with no radiographic findings is a relatively early change. Only erosion and fluffy adjacent bone resorption on plain radiography and computed tomography are specific features of active arthritis. PMID- 20585920 TI - Multidetector computed tomography venography: optimum dose of contrast material. AB - PURPOSE: The aim of this study was to determine the optimum dose of contrast material for evaluating veins in the lower limbs. MATERIALS AND METHODS: A total of 134 patients who underwent multidetector computed tomography (MDCT) due to suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) were included in this study. One hundred milliliters of iopamidol 100 ml, with 370 mg I/ml was administered. The degree of contrast enhancement of veins in the lower limbs was classified on a 4-point scale (grade 1, poor --> 4, excellent). Regions of interest (ROIs) were positioned in the femoral vein and the popliteal vein to measure CT numbers in these veins. Correlations between the CT number in each ROI and body weight were examined. RESULTS: The mean +/- SD body weights of patients by contrast-enhancement grade were as follows: grade 1, 86.3 +/- 10.2 kg; grade 2, 72.6 +/- 10.7 kg; grade 3, 59.7 +/- 8.7 kg; grade 4, 51.3 +/- 7.9 kg. Negative correlations were found between body weight and CT number for both the femoral vein and the popliteal vein. Grade 3 or better contrast enhancement was obtained in 79 of 81 patients (97.5%) weighing <60 kg. CONCLUSION: For patients weighing <60 kg, 100 ml of contrast material (370 mg I/ml) is considered sufficient for evaluating veins in the lower limbs. PMID- 20585921 TI - Once-daily radiotherapy to > or =59.4 Gy versus twice-daily radiotherapy to > or =45.0 Gy with concurrent chemotherapy for limited-stage small-cell lung cancer: a comparative analysis of toxicities and outcomes. AB - PURPOSE: The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy. MATERIALS AND METHODS: This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1) > or =59.4 Gy at 1.8-2.0 Gy per once-daily fraction or (2) > or =45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed. RESULTS: A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4-70.0 Gy) and 45 Gy (range 45-51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups ( approximately 20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4-85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice daily groups, respectively. Isolated in-field failures were similar between the two groups ( approximately 17%). CONCLUSION: The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy. PMID- 20585922 TI - Quantitative analysis of brain edema and swelling on early postmortem computed tomography: comparison with antemortem computed tomography. AB - PURPOSE: The aim of this study was quantitatively to analyze brain edema and swelling due to early postmortem changes using computed tomography (CT) scans of the head. MATERIALS AND METHODS: Review board approval was obtained, and informed consent was waived. A total of 41 patients who underwent head CT before and shortly after death were enrolled. Hounsfield units (HUs) of gray matter (GM) and white matter (WM) were measured at the levels of the basal ganglia, centrum semiovale, and high convexity area on both antemortem and postmortem CT. The length of the minor axis of the third ventricle at the level of the basal ganglia and the width of the central sulcus at the level of high convexity were measured. RESULTS: At each level tested, the HUs of GM and the GM/WM ratios on postmortem CT were significantly lower than those on antemortem CT (P < 0.001). HUs of WM on postmortem CT were slightly higher than those on antemortem CT but without significant difference (P > 0.1). Postmortem CT showed subtle loss of distinction between GM and WM. The size of the third ventricle and the width of the central sulcus did not vary before and after death (P > 0.1). CONCLUSION: Early postmortem CT shows mild brain edema but does not show brain swelling. PMID- 20585923 TI - Late gadolinium enhancement on cardiac magnetic resonance imaging: is it associated with a higher incidence of nonsustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy? AB - PURPOSE: Late gadolinium enhancement (LGE) during cardiac magnetic resonance imaging (MRI) can be seen in patients with myocardial fibrosis accompanied by myocardial infarction and cardiomyopathy. Some idiopathic dilated cardiomyopathy (DCM) patients have fibrosis in the myocardium and show LGE during cardiac MRI. The purpose of this study was to investigate the clinical significance of LGE in patients with DCM. MATERIALS AND METHODS: We recruited 32 DCM patients who had a left ventricular ejection fraction (LVEF) of <40% by echocardiography and performed cardiac MRI. LGE images were obtained 15 min after injection of Gd-DTPA (0.1 mmol/kg) using an inversion recovery gradient echo sequence. We compared LGE(+) and LGE(-) groups in terms of their nonsustained ventricular tachycardia (NSVT) properties. We also compared LGE and the frequency of an implantable cardioverter defibrillator (ICD) implantation. RESULTS: In total, 18 patients (56.3%) had LGE and a higher incidence of NSVT (P = 0.01). ICD implantation was more frequent in the LGE(+) group (P = 0.04). CONCLUSION: Because the LGE(+) patients showed a higher incidence of NSVT and ICD implantation, cardiac MRI could prove to be a useful tool in the management of DCM patients. PMID- 20585924 TI - Prospective comparison of transcatheter arterial chemoembolization with Lipiodol epirubicin and Lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma. AB - PURPOSE: The aim of this study was to compare the safety and short-term efficacy of transcatheter arterial chemoembolization (TACE) using cisplatin-Lipiodol suspension (CP/Lp) with that using epirubicin-Lipiodol emulsion (EP/Lp) in patients with recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 28 HCC patients were enrolled prospectively and assigned to the CP/Lp group or EP/Lp group. Adverse effects related to TACE were graded; and the treatment effect (TE) on HCC nodules at 3 months and overall tumor response at 6 months were assessed as the endpoint. RESULTS: No significant difference was observed between the groups regarding the frequency of adverse effects of grade 3 or less. The TE rates for 100% necrosis plus >50% necrosis in 62 HCC nodules in the CP/Lp group and 75 HCC nodules in the EP/Lp group were 72.6% and 66.7%, respectively (P = 0.894). Overall tumor response revealed that six patients (50.0%) in the CP/Lp group and six patients (37.5%) in the EP/Lp group had a partial response plus a complete response, with no significant difference (P = 0.615). TACE-free control curves for both groups revealed no significant difference (P = 0.513). CONCLUSION: No significant difference was found with regard to adverse effects, the treatment effect on HCC nodules, or overall tumor response between the CP/Lp and EP/Lp groups. PMID- 20585925 TI - Leiomyoma in a female urethral diverticulum. AB - Neoplasms arising within urethral diverticula are rare. It is important to know if a diverticulum is filled by tumor, but traditional diagnostic methods, such as voiding cystourethrography, cannot detect a tumor or diverticulum, as in our case. We report an unusual case of leiomyoma developing in a female urethra diverticulum and review the literature. PMID- 20585926 TI - Malignant transformation of a mature cystic teratoma of the ovary with rupture. AB - Malignant transformation or tumor rupture is a rare complication of ovarian mature cystic teratomas. We present computed tomography (CT) images of a 52-year old woman that revealed a large, predominantly cystic mass filled with fat and enhanced solid components located in the lower abdomen. Ten days later, the cystic mass ruptured, and massive ascites was observed on magnetic resonance imaging (MRI). Resulting from the rupture, MRI revealed reduced size and thickening wall of the tumor. After resection, the mass ruptured, and malignant transformation (squamous cell carcinoma) was observed. To our knowledge, there are no reports describing before and after images of a ruptured cystic teratoma with malignant transformation. PMID- 20585927 TI - Zygomycotic invasion of the central nervous system. AB - Zygomycosis is an opportunistic fungal infection that affects the central nervous system (CNS). In this report, we present three cases of zygomycosis with CNS involvement. In two patients zygomycosis developed after neurosurgery, and in the third patient zygomycosis developed after bone marrow transplantation for leukemia. All patients developed persistent fever and neurological deficits. They presented with progressive cerebral infarction accompanied by hemorrhage. Intraoperative findings and histopathological examinations revealed that zygomycotic hyphae caused mycotic aneurysm, vasculitis, and venous occlusion. PMID- 20585928 TI - Spontaneous splenic rupture due to extensive venous malformation with consumptive coagulopathy: treatment with splenic artery embolization. AB - Extensive venous malformation (VM) is often associated with chronic consumptive coagulopathy, which may result in bleeding complications. We report herein the case of a 25-year-old man with extensive VM involving the left lower extremity who presented with hypovolemic shock and abdominal distension without abdominal trauma. Abdomen computed tomography revealed splenic rupture with massive hemoperitoneum. He was managed successfully by repeated splenic artery embolization. PMID- 20585929 TI - Radiation therapy for B-cell cutaneous lymphoid hyperplasia. AB - Recent work has demonstrated that B-cell cutaneous lymphoid hyperplasia (BCCLH) lies in a spectrum of B-cell lymphoproliferative disorders that can progress to primary cutaneous B-cell lymphoma (CBCL). In light of this work, definitive therapy with methods such as radiotherapy is an important part of the treatment strategy. Few outcome data exist for patients with treatment-resistant BCCLH. We present a case study of a 63-year-old woman with BCCLH who failed immunomodulatory treatment but responded well to an aggressive course of radiotherapy. After 18 fractions of 6 MeV electron beam therapy with 200 cGy per fraction, the patient has been recurrence-free for 3 years. Acute toxicity was limited to Radiation Therapy Oncology Group grade II skin toxicity, which resolved within 1 month of treatment. PMID- 20585930 TI - Osteoradionecrosis of the cervical vertebrae in patients irradiated for head and neck cancers. AB - Osteoradionecrosis (ORN) is one of the common late adverse effects that follow radiation therapy for head and neck cancers. ORN usually develops on the mandible and less frequently on the maxilla. We present three cases of ORN of the cervical vertebrae, which is rarely reported. Two patients suffered from secondary osteomyelitis after neoadjuvant chemotherapy followed by definitive concurrent chemoradiation therapy with a hyperfractionated and an accelerated hyperfractionated regimen, respectively. For these patients, the high intensity of treatment was considered the cause of ORN. The third patient underwent concurrent chemoradiation therapy for upper thoracic esophageal cancer and subsequently underwent endoscopic laser resection and radiation therapy for hypopharyngeal cancer. ORN developed in the area of reirradiation. In this case, an excessive radiation dose was considered the cause. ORN of cervical vertebrae, different from that of the mandible and maxilla, has a risk of radiculopathy and myelopathy. In the future, ORN of cervical vertebrae will increase because metachronous double cancers will increase and opportunities for reirradiation, in turn, will increase. To prevent this, it is necessary to optimize the treatment schedule for radiation therapy, including the total dose, fractionation, and concurrent chemotherapy, and to decrease the volume of cervical vertebrae within the irradiation field. PMID- 20585931 TI - Massive bleeding of ruptured metastatic hepatic melanoma treated by transarterial embolization. AB - Although melanoma frequently metastasizes to the liver, its spontaneous rupture is rare. We report herein an unusual case of a 73-year-old man with rupture of multiple hepatic metastases from scalp melanoma and resulting massive intraperitoneal bleeding, which was successfully controlled by transarterial embolization. PMID- 20585932 TI - Estimation of organs doses and radiation-induced secondary cancer risk from scattered photons for conventional radiation therapy of nasopharynx: a Monte Carlo study. AB - PURPOSE: We used Monte Carlo modeling to calculate the organs doses due to out-of field photons during radiation therapy of the nasopharynx. MATERIALS AND METHODS: A medical internal radiation dose (MIRD)-based mathematical phantom resembling an adult man was modeled by MCNP4C MC code. Three validated models of a cobalt-60 machine, a 6-MV photon beam of a Varian 2300 C/D linac, and a 9-MV photon beam of a Neptun linac were used to simulate the isocentric irradiation of a mathematical phantom with two lateral fields of the nasopharynx. The organspecific dose, effective dose, and cancer risk estimates were obtained. RESULTS: The effective doses for out-of-field radiation were 320, 295, and 248 mSv for the (60)Co beam, 6-MV beam, and 9-MV beam devices, respectively, for a 70-Gy tumor dose. The fatal cancer risks of 1.6%, 1.5%, and 1.2% were estimated for a 70-Gy tumor dose of (60)Co and the 6- and 9-MV photon beams, respectively. CONCLUSION: Our results regarding the effective dose and cancer risk are in agreement with previously published experimental results on conventional radiation therapy. Further investigation on patients' out-of-field dose to provide more knowledge on various radiotherapy techniques is suggested. PMID- 20585933 TI - Nocturnal hypoglycaemia presenting as somnambulism. PMID- 20585934 TI - Lineage tracing and resulting phenotype of haemopoietic-derived cells in the pancreas during beta cell regeneration. AB - AIMS: Transplantation of bone marrow-derived haemopoietic stem cells following streptozotocin (STZ) treatment to induce pancreatic beta cell loss in mice causes the partial regeneration of beta cell mass, with many haemopoietic cells demonstrating endothelial cell markers. This study used genetically tagged haemopoietic lineage-derived cells to determine how endogenous cells are mobilised following beta cell loss and subsequent replacement. METHODS: A double transgenic mouse model, Vav-iCre; R26R-enhanced yellow fluorescent protein (YFP), was used where only haemopoietic lineage cells expressed the Vav1 gene promoter allowing expression of the YFP reporter gene. Between postnatal days 2 and 4 mice were injected with STZ or vehicle (control) and body weight and glycaemia were monitored. Mice were killed between days 10 and 130, and the pancreases were examined by immunofluorescence microscopy. RESULTS: YFP-expressing cells infiltrated the pancreas at all ages, being present around newly forming islets at the pancreatic ducts, and within larger islets. Small numbers of YFP-positive cells (<5%) co-stained for the macrophage markers F4/80 or Mac1, for cytokeratin 19, or for the transcription factor pancreatic and duodenal homeobox 1 (PDX-1), but no co-localisation was seen with insulin or other endocrine hormones. Within islets approximately 30% of YFP-positive cells co-stained for the endothelial cell marker CD31, and following STZ the number of haemopoietic-derived cells, and the proportion that were CD31-positive, both significantly increased after 21 and 40 days, coincident with a partial replacement of beta cells. CONCLUSIONS: Our results suggest that following beta cell loss endogenous haemopoietic-lineage cells contribute to intra-islet angiogenesis, which supports a partial recovery of beta cell mass. PMID- 20585935 TI - High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats. AB - AIMS/HYPOTHESIS: Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP). METHODS: Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum. An OGTT was performed every 10 days and histological and immunofluorescence evaluations of the duodenum were obtained at 60 days from the beginning of the diets. Plasma glucose, insulin, GIP and glucagon-like peptide-1 (GLP-1) levels were measured. Immunofluorescence analysis of duodenal sections for pancreatic duodenal homeobox-1 (PDX-1), KI67, GLP-1, GIP and insulin were performed. RESULTS: Compared with chow diet, HFD induced a progressive significant increase of the glucose, insulin and GIP responses to OGTT, whereas GLP-1 circulating levels were reduced over time. After 60 days of HFD, cellular agglomerates of KI67 and PDX-1 positive cells, negative for insulin and GLP-1 but positive for GIP staining, were found inside the duodenal mucosa, and apoptosis was significantly increased. CONCLUSIONS/INTERPRETATION: With the limitation that we could not establish a causal relationship between events, our study shows that HFD stimulates duodenal proliferation of endocrine cells differentiating towards K cells and oversecreting GIP. The progressive increment of GIP levels might represent the stimulus for insulin hypersecretion and insulin resistance. PMID- 20585936 TI - Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes. AB - AIMS/HYPOTHESIS: Gastrin has been implicated in islet growth/neogenesis, and proton pump inhibitors (PPIs) have been shown to increase endogenous gastrin levels in animals and humans. Therefore, we investigated the effect of PPIs in a model of type 2 diabetes, Psammomys obesus. METHODS: P. obesus (morning blood glucose [mBG] 16.9 +/- 0.6 mmol/l) were treated with vehicle or different doses (1-15 mg/kg) of lansoprazole for 17 days. RESULTS: Treatment with lansoprazole resulted in up to ninefold dose-dependent increases in endogenous gastrin levels (p < 0.05 for 10 mg/kg lansoprazole vs vehicle). There was a significant reduction in mBG levels in all animals in the high-dose lansoprazole groups during the 17 day treatment period, whereas there was no significant improvement in mBG in animals in the vehicle groups. The mBG at end of study was 18.2 +/- 2.1, 8.7 +/- 2.2 (p < 0.01), and 6.1 +/- 2.3 (p < 0.001) mmol/l for vehicle and lansoprazole 10 and 15 mg/kg, respectively. The animals treated with 15 mg/kg lansoprazole, compared with vehicle, had a 2.3-fold increase in the intensity of insulin staining in beta cells (p=0.0002) and 50% higher beta cell mass (p=0.04). CONCLUSIONS/INTERPRETATIONS: The PPI lansoprazole had significant glucose lowering effects in an animal model of type 2 diabetes, an effect that is most likely mediated through an increase in endogenous gastrin levels. PMID- 20585937 TI - Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. AB - Previous studies evaluated the association between proton pump inhibitor (PPI) use and subsequent fracture risk, but they showed ambiguous results. Therefore, the objective was to evaluate this association in a different study population. Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. INTRODUCTION: Previous studies evaluated the association between PPI use and subsequent fracture risk, but they showed ambiguous results. To further test these conflicting results, the objective of this study was to evaluate the association between the use of PPIs and the risk of hip/femur fracture in a different study population. METHODS: A case-control study was conducted using data from the Dutch PHARMO record linkage system. The study population included 6,763 cases aged 18 years and older with a first hip/femur fracture during enrollment and 26,341 age-, gender- and region-matched controls. RESULTS: Current users of PPIs had an increased risk of hip/femur fracture yielding an adjusted odds ratio (AOR) of 1.20 (95% CI 1.04-1.40). Fracture risk attenuated with increasing durations of use, resulting in AORs of 1.26 (95% CI 0.94-1.68) in the first 3 months, 1.31 (95% CI 0.97-1.75) between 3 and 12 months, 1.18 (95% CI 0.92-1.52) between 13 and 36 months and 1.09 (95% CI 0.81 1.47) for use longer than 36 months. CONCLUSION: Our findings show that there is probably no causal relationship between PPI use and hip fracture risk. The observed association may be the result of unmeasured distortions: although current use of PPIs was associated with a 1.2-fold increased risk of hip/femur fracture, the positive association was attenuated with longer durations of continuous use. Our findings do not support that discontinuation of PPIs decreases risk of hip fracture in elderly patients. PMID- 20585938 TI - Low bone mineral density is associated with increased mortality in elderly men: MrOS Sweden. AB - SUMMARY: We studied the nature of the relationship between bone mineral density (BMD) and the risk of death among elderly men. BMD was associated with mortality risk and was independent of adjustments for other co-morbidities. A piecewise linear function described the relationship more accurately than assuming the same gradient of risk over the whole range of BMD (p = 0.020). Low BMD was associated with a substantial excess risk of death, whilst a higher than average BMD had little impact on mortality. INTRODUCTION: Previous studies have demonstrated an association between low BMD and an increased risk of death among men and women. The aim of the present study was to examine the pattern of the risk in men and its relation to co-morbidities. METHODS: We studied the nature of the relationship between BMD and death among 3,014 elderly men drawn from the population and recruited to the MrOS study in Sweden. Baseline data included general health questionnaires, life style questionnaires and BMD measured using DXA. Men were followed for up to 6.5 years (average 4.5 years). Poisson regression was used to investigate the relationship between BMD, co-morbidities and the hazard function of death. RESULTS: During follow-up, 382 men died (all cause mortality). Low BMD at all measured skeletal sites was associated with increased mortality. In multivariate analyses, the relationship between BMD and mortality was non-linear, and a piecewise linear function described the relationship more accurately than assuming the same gradient of risk over the whole range of BMD (p = 0.020). CONCLUSIONS: Low BMD is associated with a substantial excess risk of death compared to an average BMD, whereas a higher than average BMD has a more modest effect on mortality. These findings, if confirmed elsewhere, have implications for the constructing of probability-based fracture risk assessment tools. PMID- 20585939 TI - Vitamin D deficiency in HIV-infected postmenopausal Hispanic and African-American women. AB - We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy. INTRODUCTION: To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women. METHODS: In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry. RESULTS: The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART. CONCLUSIONS: In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients. PMID- 20585940 TI - Quantitative ultrasound and radiographic absorptiometry are associated with vertebral deformity in Japanese Women: the Hizen-Oshima study. AB - We evaluated the ability of heel quantitative ultrasound (QUS) and metacarpal radiographic absorptiometry (RA) to identify subjects with vertebral deformities in Japanese women aged >=40. Both QUS and RA were associated with vertebral deformities, and the estimated prevalence at each T-score widely varied with age. INTRODUCTION: Heel QUS and metacarpal RA have been used for screening patients to evaluate risk of osteoporotic fractures. The aim of this study was to evaluate the ability of QUS and RA to identify women with vertebral deformities in 570 Japanese women aged >=40, and to estimate the prevalence of vertebral deformity at each T-score. METHODS: Calcaneal QUS and metacarpal RA were performed. Radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. RESULTS: The receiver operating characteristic analysis showed that both calcaneal stiffness index (SI) and metacarpal bone mineral density (BMD) were associated with vertebral deformities. Using the T-score of -2.5 as a cutoff value, the specificity and sensitivity for identifying individuals with vertebral deformities was 65% and 83% for calcaneal SI, and 40% and 88% for metacarpal BMD, respectively. The prevalence of vertebral deformity was estimated using age adjusted logistic regression models. Women with calcaneal SI T-score of -2.5 had a 2% estimated probability of vertebral deformity at age 40, and 22% at age 80. For metacarpal BMD T-score of -2.5, estimated probability was less than 1% at age 40, and 27% at age 80. CONCLUSION: Both calcaneal SI and metacarpal BMD were associated with prevalence of vertebral deformity. Furthermore, the prevalence widely varied with age at any given bone value. PMID- 20585941 TI - Determination of total and non-water soluble iodine in atmospheric aerosols by thermal extraction and spectrometric detection (TESI). AB - Iodine has recently been of interest in atmospheric chemistry due to its role in tropospheric ozone depletion, modification of the HO/HO(2) ratio and aerosol nucleation. Gas-phase iodine chemistry is tightly coupled to the aerosol phase through heterogeneous reactions, which are dependent on iodine concentrations and speciation in the aerosol. To date, the only method available for total iodine determination in aerosols is collection on filters by impaction and quantification by neutron activation analysis (NAA). NAA is not widely available to all working groups and is costly to commission. Here, we present a method to determine total iodine concentrations in aerosol impact filter samples by combustion of filter sub-samples (approximately 5 cm(2)) at 1,000 degrees C, trapping in deionised water and quantification by UV/Vis spectroscopy. Both quartz and cellulose filters were analysed from four separate sampling campaigns. The method proved to be sensitive (3sigma = 6 ng absolute iodine approximately 3 pmol m(-3)) precise (RSD approximately 5%) and accurate, as determined by external and standard addition calibrations. Total iodine concentrations ranged from 10 pmol m(-3) over the Southern Ocean to 100 pmol m(-3) over the tropical Atlantic, in agreement with previous estimates. The soluble iodine concentration (extracted with water and measured by ICP-MS) was then subtracted from the total iodine to yield non-water-soluble iodine (NSI). The NSI fraction ranged from 20% to 53% of total iodine, and thus can be significant in some cases. PMID- 20585942 TI - Chromatographic separation of antiviral/anticancer nucleoside reverse transcriptase inhibitor drugs. AB - This paper discusses the current methods used for quantitative determination of analogues of nucleotide reverse transcriptase inhibitors (NtRTIs) in body fluids, cells, and tissues. Nucleoside reverse transcriptase inhibitors (NRTIs) prodrugs given to AIDS/herpes/cancer patients conjugate with phosphates at the site of their action. Separation of phosphorylated NRTIs is generally performed by reversed-phase chromatography. After separation, plasma NRTIs can be detected using a variety of methods, including immunoassay through monitoring of UV absorbance, fluorescence, and mass spectrometry. The most recent development in the field of detection of plasma NtRTIs shows a tendency toward the use double- or triple-focusing mass spectrometry, the most specific and sensitive monitoring technique. PMID- 20585943 TI - Comparative genome analysis of Prevotella ruminicola and Prevotella bryantii: insights into their environmental niche. AB - The Prevotellas comprise a diverse group of bacteria that has received surprisingly limited attention at the whole genome-sequencing level. In this communication, we present the comparative analysis of the genomes of Prevotella ruminicola 23 (GenBank: CP002006) and Prevotella bryantii B(1)4 (GenBank: ADWO00000000), two gastrointestinal isolates. Both P. ruminicola and P. bryantii have acquired an extensive repertoire of glycoside hydrolases that are targeted towards non-cellulosic polysaccharides, especially GH43 bifunctional enzymes. Our analysis demonstrates the diversity of this genus. The results from these analyses highlight their role in the gastrointestinal tract, and provide a template for additional work on genetic characterization of these species. PMID- 20585945 TI - Unusual lesion of the clivus: diagnosis and discussion. PMID- 20585946 TI - Easy method for reduction of nipple height. AB - BACKGROUND: This report presents an easy method for reducing nipple height with a buried purse-string suture. METHODS: A total of 38 nipple reductions were performed for 19 women. After the desired projection was determined, the nipple was marked for the extent of resection. A horizontal circle at 130 to 140% of the desired nipple height was drawn on the circumference of the nipple. The nipple was pulled away from the base of the nipple with a traction suture. Following the incision through the marked line, nipple bulk was dissected from the core of the nipple. Nipple tissue was excised piece by piece, starting from the periphery and proceeding toward the center, around the circumference of nipple. A buried purse string suture with absorbable suture brought the remaining flaps closer together and reduced nipple diameter. The knot was deeply buried under the tip of the approximated nipple flap. RESULTS: For 14 patients (28 nipples) of 19 patients (38 nipples), the final nipple height ranged within 90 to 110% of the intended height at the last follow-up visit after a mean period of 18 months. Of the 19 women, 14 were satisfied with the final nipple height. CONCLUSION: The authors' surgical method is primarily aimed at reducing the nipple height and has some limitations in reducing the diameter of the nipple. However, circumferential resection of the nipple core effectively reduces muscle bulk in the remaining nipple and has a secondary effect of reducing nipple diameter. PMID- 20585947 TI - Preventing the "bottoming out and star-gazing" phenomenon in inferior pedicle breast reduction with an acellular dermal matrix internal brassiere. PMID- 20585948 TI - CacyBP/SIP expression is involved in the clinical progression of breast cancer. AB - OBJECTIVE: Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is a target protein of the S100A6, which is a member of the S100 family. It has been shown that CacyBP/SIP plays important roles in cell cycle progression, differentiation, and carcinogenesis. The purpose of this study was to explore the correlation of CacyBP/SIP expression and clinical significance in breast cancer. METHODS: Immunohistochemistry was performed to detect the CacyBP/SIP expression in 79 pairs of breast cancer tissues and adjacent nontumor tissues. Western blot analysis and semiquantitative RT-PCR were used to measure CacyBP/SIP protein and mRNA levels in three pairs of fresh breast cancer tissues and adjacent nontumor tissues. The clinical data were collected by telephone follow-up for 5 years. RESULTS: CacyBP/SIP mRNA and protein levels in breast cancer tissues were significantly higher compared with adjacent nontumor tissues. Poor cellular differentiation, lymph node invasion, and clinicopathological staging in breast cancer were associated with CacyBP/SIP expression. Other factors, such as age, menses, and tumor size, were not related to CacyBP/SIP expression. The up regulation of CacyBP/SIP expression also was shown to increase recurrence and metastasis of breast cancer and to correlate with short overall survival rate. CONCLUSIONS: CacyBP/SIP expression is evident in more advanced clinical progression of breast cancer, and it might be a biomarker for poor prognosis and a potential therapeutic target in breast cancer. PMID- 20585949 TI - Current opinions on endosperm transfer cells in maize. AB - Endosperm transfer cells (ETC) mainly occur in the endosperm epithelial layer near the pedicel. They transport the nutrient unloaded by the maternal vascular tissue to filial tissues. Wall ingrowths of ETC can facilitate solute transportation. Sugar, especially glucose, is found to modulate the promoter activity of ZmMRP-1, a determinant of transfer cell-specific expression. The ZmMRP-1-encoded protein can transactivate the promoters of transfer cell-specific genes. Signalling and early events leading to wall ingrowth formation depend upon gene expression. Sucrose synthase and the cytoskeleton probably play a primary role in the wall ingrowth formation. The major solutes transferred by ETC are amino acids, sucrose, and monosaccharides, which is consistent with the expression of their transporters and transport-associated genes. In this paper, we review current opinions on the differentiation, wall ingrowth formation, and function of ETC in maize. According to the experimental materials provided by predecessors, we also give some speculations about the differentiation mechanisms of ETC and process of wall ingrowth formation. PMID- 20585950 TI - Added salt helps sunbirds and honeyeaters maintain energy balance on extremely dilute nectar diets. AB - Nectar-feeding birds ingest excess water and risk loss of solutes when they excrete it. Previous work has shown that white-bellied sunbirds (Cinnyris talatala) are unable to maintain energy balance on extremely dilute sucrose diets without salts (e.g. <0.25 mol l(-1)), and that they lose more electrolytes (i.e. Na(+) and K(+)) via cloacal fluid on these diets than on more concentrated diets. Using white-bellied sunbirds and New Holland honeyeaters (Phylidonyris novaehollandiae) we tested the effect of adding electrolytes to a 0.1 mol l(-1) sucrose diet, by including equimolar NaCl and KCl at concentrations from 5 to 40 mmol l(-1) and the individual salts at 20 mmol l(-1). Addition of salts enabled both species to drink significantly more of the 0.1 mol l(-1) sucrose diet than in the absence of salts, and mass loss during the experiment was reduced when salt was included. The larger honeyeaters may be more susceptible to electrolyte depletion than the smaller sunbirds. On 20 mmol l(-1) combined salts, both sunbirds and honeyeaters consumed eight times their body mass in fluid daily. KCl alone had no effect. Birds are thus limited in their consumption of extremely dilute diets by increasing losses of Na(+). This was confirmed by measuring plasma Na(+) levels, which decreased in both species in the absence of dietary Na(+). In addition, sucrose assimilation efficiencies were slightly, but significantly lower when sunbirds were fed salt-free diet, while glucose levels in ureteral urine remained extremely low. It is concluded that Na(+) depletion on very dilute salt-free diets does not affect Na(+)-glucose transport activity in the kidney, but interferes with sugar digestion and/or assimilation in the intestine. PMID- 20585951 TI - Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies. AB - PURPOSE: To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria. METHODS: A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events. RESULTS: Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis--a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies. CONCLUSIONS: Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes. PMID- 20585952 TI - Characteristics and prognosis of coexisting adnexa malignancy with endometrial cancer: a single institution review of 51 cases. AB - OBJECTIVE: To explore and compare the differences in the clinicopathological characteristics and prognosis of synchronous primary endometrial and ovarian cancers with primary endometrial cancer metastatic to adnexa. MATERIALS AND METHODS: Between January 1997 and December 2009, 51 cases with endometrial cancer simultaneously with adnexa malignancy were identified. Among them, there were 18 cases with synchronous primary cancers of the endometrium and ovary (Group A) and 33 cases with primary endometrial cancer metastatic to the adnexa (Group B). Clinical and pathologic information was obtained from medical records. Parametric methods were used to compare clinical and pathologic features. Kaplan-Meier survival analysis was performed and compared using log-rank test. RESULTS: The mean age at diagnosis of the disease was 56.6 +/- 10.8 years (range 34-76 years) in Group A and 53.1 +/- 9.5 years (range 37-76 years) in Group B. The two groups' distribution of preoperative image findings, size of endometrial lesion, myometrial invasion, unilateral or bilateral, cervix invasion, and postoperative radiation existed significant differences. With a mean follow-up time of 4.3 +/- 3.4 years (range 2-11 years), 5-year overall survival (OS) was 75 and 56% in Groups A and B, respectively (p = 0.034). The univariate analysis showed only postoperative radiation and synchronous tumors were independent factors which affected OS (p = 0.015; p = 0.034) and progression-free survival (PFS) (p = 0.015; p = 0.036), respectively. Not any feature was revealed by multivariate analysis as independent prognostic factors. CONCLUSION: Our results showed that OS and PFS of synchronous primary ovarian cancer in patients with endometrial cancer is better than those with ovarian metastasis patients. Pre- and intra operative, intensive and careful assessment, and strict and continuous postoperative surveillance should pay attention to the endometrial cancer patients who preserved ovary for having possibility of coexisting occult ovarian lesions. PMID- 20585953 TI - A Japanese physician's experience as an inpatient in the United States and Japan. PMID- 20585954 TI - Huntington's disease: changes in saccades and hand-tapping over 3 years. AB - Saccades and hand-tapping are both potential biomarkers in patients with Huntington's disease (HD). While it is well known that patients with manifest Huntington's disease display abnormalities in both of these tasks, less is known about how these abnormalities progress over time, or to what extent premanifest patients are affected. This study was designed to address these issues. We examined premanifest and manifest Huntington's cohorts, together with a group of controls, over a 3-year period. Data were collected using a portable head-mounted saccadometer and a computerised hand-tapping device. Both premanifest and manifest Huntington's disease patients display significant and systematic changes from year to year in the parameters describing saccadic latency, while controls remain unchanged. By contrast, although hand-tapping was abnormal in HD patients, annual changes were much smaller. Measuring the rate of progression of saccadic abnormalities in manifest HD patients may provide a way to track disease progression, and thus help to evaluate novel therapies to modify the disease. The clear-cut progression in saccadic abnormalities in the premanifest group may prove useful in the future as a predictor of time to disease onset. PMID- 20585955 TI - Bernd Nilius: the bard of ion channels. Congratulations on 65th birthday. PMID- 20585956 TI - Epac stimulation induces rapid increases in connexin43 phosphorylation and function without preconditioning effect. AB - It has been recently shown that beta-adrenergic receptors are able to activate phospholipase C via the cyclic adenosine monophosphate-binding protein Epac. This new interconnection may participate in isoproterenol (Iso)-induced preconditioning. We evaluated here whether Epac could induce PKCepsilon activation and could play a role in ischemic preconditioning through the phosphorylation of connexin43 (Cx43) and changes in gap junctional intercellular communication (GJIC). In cultured rat neonatal cardiomyocytes, we showed that in response to Iso and 8-CPT, a specific Epac activator, PKCepsilon content was increased in particulate fractions of cell lysates independently of protein kinase A (PKA). This was associated with an increased Cx43 phosphorylation. Both Iso and 8-CPT induced an increase in GJIC that was blocked by the PKC inhibitor bisindolylmaleimide. Interestingly, inhibition of PKA partly suppressed both Iso induced increases in Cx43 phosphorylation and in GJIC. The same PKCepsilon dependent Cx43 phosphorylation by beta-adrenergic stimulation via Epac was found in adult rat hearts. However, in contrast with Iso that induced a preconditioning effect, perfusion of isolated hearts with 8-CPT prior to ischemia failed to improve the post-ischemia functional recovery. In conclusion, Epac stimulation induces PKCepsilon activation and Cx43 phosphorylation with an increase in GJIC, but Epac activation does not induce preconditioning to ischemia in contrast with beta-adrenergic stimulation. PMID- 20585958 TI - Single-incision laparoscopic surgery (SILSTM) versus standard laparoscopic surgery: a comparison of performance using a surgical simulator. AB - BACKGROUND: Single-incision laparoscopic surgery (SILSTM) is a potentially less invasive approach than standard laparoscopy (LAP). However, SILSTM may not allow the same level of manual dexterity and technical performance compared to LAP. We compared the performance of standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS) program using either the LAP or the SILSTM technique. METHODS: Medical students, surgical residents, and attending physicians were recruited and divided into inexperienced (IE), laparoscopy-experienced (LE), and SILSTM-experienced (SE) groups. Each subject performed standardized tasks from FLS, including peg transfer, pattern cutting, placement of ligating loop, and intracorporeal suturing using a standard three-port FLS box-trainer with standard laparoscopic instruments. For SILSTM, the subjects used an FLS box-trainer modified to accept a SILS PortTM with two working ports for instruments and one port for a 30 degrees 5-mm laparoscope. SILSTM tasks were performed with instruments capable of unilateral articulation. SILSTM suturing was performed both with and without an articulating EndoStitchTM device. Task scores, including cumulative laparoscopic FLS score (LS) and cumulative SILSTM FLS score (SS), were calculated using standard time and accuracy metrics. RESULTS: There were 27 participants in the study. SS was inferior to LS in all groups. LS increased with experience level, but was similar between LE and SE groups. SS increased with experience level and was different among all groups. SILSTM suturing using the articulating suturing device was superior to the use of a modified needle driver technique. CONCLUSIONS: SILSTM is more technically challenging than standard laparoscopic surgery. Using currently available SILSTM platforms and instruments, even surgeons with SILSTM experience are unable to match their overall LAP performance. Specialized training curricula should be developed for inexperienced surgeons who wish to perform SILSTM. PMID- 20585957 TI - Centromere identity: a challenge to be faced. AB - The centromere is a genetic locus, required for faithful chromosome segregation, where spindle fibers attach to the chromosome through kinetochore. Loss of centromere or formation of multiple centromeres on a single chromosome leads to chromosome missegregation or chromosome breakage, respectively, which are detrimental for fitness and survival of a cell. Therefore, understanding the mechanism of centromere locus determination on the chromosome and perpetuation of such a locus in subsequent generation (known as centromere identity) is very fundamental to combat conditions like aneuploidy, spontaneous abortion, developmental defects, cell lethality and cancer. Recent studies have come up with different models to explain centromere identity. However, the exact mechanism still remains elusive. It has been observed that most eukaryotic centromeres are determined epigenetically rather than by a DNA sequence. The epigenetic marks that are instrumental in determining centromere identity are the histone H3 variant, CENP-A and the specialized posttranslational modification of the core histones. Here we will review the recent studies on the factors responsible for generating unique centromeric chromatin and how it perpetuates during cell division giving the present-day models. We will further focus on the probable mechanism of de novo centromere formation with an example of neocentromere. As a matter of similitude, this review will include marking extrachromosomal chromatin to be served as a partitioning locus by deposition of CENP-A homolog in budding yeast. PMID- 20585959 TI - Fifteen years experience in laparoscopic inguinal hernia repair in pediatric patients. Results and considerations on a debated procedure. AB - BACKGROUND: Laparoscopic inguinal hernia repair is rarely reported in pediatric patients. We report our 15-year experience on this topic to show the long-term results of this technique. METHODS: During a 15-year period, we operated 596 boys for unilateral inguinal hernia using laparoscopy. The age range was variable from 6 months to 15 years (median, 54 months), with a median body weight of 18.5 (range, 8-54) kg. Preoperatively, 352 boys had a right hernia and 172 had a left hernia. We always used three trocars. We used the laparoscopic herniorrhaphy described by our group 15 years ago; it consists of sectioning the sac distally to the inguinal ring and performing a pursestring suture around the periorificial peritoneum using a 4/0 nonresorbable suture. RESULTS: The median operating time was 19 min. All procedures were performed in a day-hospital setting. As for laparoscopic findings in 95 of 596 patients (15.9%), we found a contralateral patency of the processus vaginalis. In these 95 cases, we performed bilateral herniorrhaphy. In 7 of 596 patients (1.2%), we discovered a direct hernia. With follow-up between 1 and 15 years, we have only 11 recurrences (1.5%)-all reoperated by laparoscopy. CONCLUSIONS: We believe that laparoscopic repair of inguinal hernia performed by expert hands is a safe and effective procedure to perform with long-term follow-up. Its ability to repair simultaneously all forms of inguinal hernias together with contralateral patencies has cemented its role as a viable alternative to conventional repair. PMID- 20585960 TI - Construct validity of the LapVR virtual-reality surgical simulator. AB - BACKGROUND: Laparoscopic surgery requires fundamental skills peculiar to endoscopic procedures such as eye-hand coordination. Acquisition of such skills prior to performing actual surgery is highly desirable for favorable outcome. Virtual-reality simulators have been developed for both surgical training and assessment of performance. The aim of the current study is to show construct validity of a novel simulator, LapVR (Immersion Medical, San Jose, CA, USA), for Japanese surgeons and surgical residents. METHODS: Forty-four subjects were divided into the following three groups according to their experience in laparoscopic surgery: 14 residents (RE) with no experience in laparoscopic surgery, 14 junior surgeons (JR) with little experience, and 16 experienced surgeons (EX). All subjects executed "essential task 1" programmed in the LapVR, which consists of six tasks, resulting in automatic measurement of 100 parameters indicating various aspects of laparoscopic skills. RESULTS: Time required for each task tended to be inversely correlated with experience in laparoscopic surgery. For the peg transfer skill, statistically significant differences were observed between EX and RE in three parameters, including total time and average time taken to complete the procedure and path length for the nondominant hand. For the cutting skill, similar differences were observed between EX and RE in total time, number of unsuccessful cutting attempts, and path length for the nondominant hand. According to the programmed comprehensive evaluation, performance in terms of successful completion of the task and actual experience of the participants in laparoscopic surgery correlated significantly for the peg transfer (P=0.007) and cutting skills (P=0.026). CONCLUSIONS: The peg transfer and cutting skills could best distinguish between EX and RE. This study is the first to provide evidence that LapVR has construct validity to discriminate between novice and experienced laparoscopic surgeons. PMID- 20585961 TI - Benefits of endoscopic submucosal dissection in rectal polyps are unclear. PMID- 20585962 TI - Laparoscopic resection for rectal cancer: a case-matched study. AB - INTRODUCTION: The field of laparoscopic rectal cancer surgery is expanding. We compare short-term and early oncological outcomes after laparoscopic versus open resection in carefully matched rectal cancer patients. METHODS: All consecutive patients undergoing elective laparoscopic resection for rectal cancer were reviewed. Laparoscopic resections were matched 1:1 to open resections by age, gender, American Society of Anesthesiologists class, body mass index, neoadjuvant chemoradiation, and type of surgery. Data were analyzed using Fisher's exact, chi square, Wilcoxon rank-sum tests, and Kaplan-Meier estimates. P-value <0.05 was considered statistically significant. RESULTS: Ninety-one rectal cancer patients with laparoscopic resection were included, 59% were male, and median age was 62 years. Conversion rate was 18.7%. Laparoscopic and open surgery had similar 30 day morbidity and mortality except wound infection, which was lower for the laparoscopic group (p = 0.02). Laparoscopic surgery had similar 30-day readmissions but shorter total length of hospital stay (5 versus 7 days, p < 0.01), time to first flatus (3 versus 4.5 days, p = 0.001), and time to first bowel movement (4 versus 5 days, p = 0.05) when compared with open surgery. The 3 year disease-free survival, local recurrence, and distant recurrence rates were also similar between the two groups. CONCLUSION: Laparoscopic surgery can be safely performed for rectal cancer, with better postoperative recovery and acceptable early oncological outcomes. Results from large ongoing randomized trials with longer follow-up time are pending to better define oncologic outcomes. PMID- 20585963 TI - Feasibility of laparoscopic Nissen fundoplication after pediatric lung or heart lung transplantation: should this be the standard? AB - BACKGROUND: Five-year graft survival in the pediatric lung transplant (LTxp) population is less than 50%, with obliterative bronchiolitis (OB) the leading cause of death at 1, 3, and 5 years post-transplant. Bronchiolitis obliterans syndrome (BOS), defined using spirometry values, is the clinical surrogate for the histological diagnosis of obliterative bronchiolitis. Surgical correction of documented gastroesophageal reflux disease (GERD) has been proposed as a means to potentially delay the onset of BOS and prolong allograft survival in adults before or after lung transplantation but only one such study exists in children. We have examined the safety and possible benefits of laparoscopic antireflux surgery in pediatric patients following lung (LTxp) and heart-lung transplantation (HLTxp). METHODS: An Institutional Review Board (IRB)-approved retrospective chart review was performed to evaluate the outcomes and complications of laparoscopic antireflux surgery in pediatric lung and heart-lung transplant patients. Spirometry data were collected for BOS staging using BOS criteria for children. RESULTS: Twenty-five lung and heart-lung transplants were performed between January 2003 and July 2009. Eleven transplant recipients, including six double-lung and five heart-lung (HLTxp), with a median age of 11.7 years (range 5.1-18.4 years), underwent a total of 12 laparoscopic Nissen fundoplications at a median of 427 days after transplant (range 51-2310 days). GERD was determined based upon clinical impression, pH probe study, gastric emptying study, and/or esophagram in all patients. Three patients already had a gastrostomy tube in place and two had one placed at the time of fundoplication. There were no conversions to open surgery, 30-day readmissions, or 30-day mortalities. Complications included one exploratory laparoscopy for free air 6 days after laparoscopic Nissen fundoplication for a gastric perforation that had spontaneously sealed. Another patient required a revision laparoscopic Nissen 822 days following the initial fundoplication for a paraesophageal hernia and recurrent GERD. The average length of hospital stay was 4.4 +/- 1.7 days. Nine of the 12 fundoplications were performed in patients with baseline spirometry values prior to fundoplication and who could also complete spirometry reliably. One of these nine operations was associated with improvement in BOS stage 6 months after fundoplication; seven were associated with no change in BOS stage; and one was associated with a decline in BOS stage. CONCLUSION: It is feasible to perform laparoscopic Nissen fundoplication in pediatric lung and heart-lung transplant recipients without mortality or significant morbidity for the treatment of GERD. The real effect on pulmonary function cannot be assessed due to our small sample size and lack of reproducible spirometry in our younger patients. Additional studies are needed to elucidate the relationship between antireflux surgery and the potential for improving pulmonary allograft function and survival in children which has been previously observed in adult patients. PMID- 20585964 TI - Measuring learning gain during a one-day introductory bronchoscopy course. AB - BACKGROUND: Rigorous assessment of medical knowledge and technical skill inspires learning, reinforces confidence, and reassures the public. Identifying curricular effectiveness using objective measures of learning is therefore crucial for competency-oriented program development in a learner-centric educational environment. The aim of this study was to determine whether various measures of learning, including class-average normalized gain, can be used to assess the effectiveness of a one-day introductory bronchoscopy course curriculum. METHODS: We conducted a quasi-experimental one-group pre-test/post-test study at the University of California, Irvine. The group comprised 24 first-year pulmonary and critical care trainees from eight training institutions in southern California. Class-average normalized gain, single-student normalized gain, absolute gain, and relative gain were used as objective measures of cognitive knowledge and bronchoscopy technical skill learning. A class-average normalized gain of 30% was used to determine curricular effectiveness. Perceived educational value using Likert-scale surveys and post-course questionnaires was determined during and 3 months after course participation. RESULTS: Mean test scores of cognitive knowledge improved significantly from 48 to 66% (p = 0.043). Absolute gain for the class was 18%, relative gain was 37%, class average normalized gain was 34%, and the average of the single-student normalized gains g(ave) was 29%. Mean test scores of technical skill improved significantly from 43 to 77% (p = 0.017). Absolute gain was 34%, relative gain was 78%, class average normalized gain was 60%, and the average of the single-student normalized gains g(ave) was 59%. Statistically significant improvements in absolute gain were noted in all five elements of technical skill (p < 0.05). Likert-scale surveys, questionnaires, and surveys demonstrated strong perceived educational value. CONCLUSION: The effectiveness of a one-day introductory bronchoscopy curriculum was demonstrated using a pre-test/post-test model with calculation of normalized gain and related metrics. PMID- 20585965 TI - Lateral tethering intraspinal lipoma with scoliosis. AB - The authors present an unusual case of an intradural lipoma at the thoracolumbar level causing lateral tethering of the spine, with complicated scoliosis. A 6 year-old girl was admitted with progressive change in posture detected by her parents. Thoracolumbar scoliosis was detected by physical examination and X-ray studies. Spinal magnetic resonance imaging revealed an intradural lipoma and right lateral tethering of the spine at the upper lumbar level. After surgical release of lateral tethering and resection of the lipoma, fusion was performed by the orthopedic surgery team. Radiological and intraoperative findings of this extremely rare case are discussed. PMID- 20585966 TI - Surgical treatment of infectious spondylitis in patients undergoing hemodialysis therapy. AB - Treatment of infectious spondylitis in hemodialysis patients remains a challenge because of comorbidities. This study aimed to evaluate the impact of end-stage renal disease (ESRD) on the clinical manifestations and surgical outcomes of patients with spinal infection. Sixteen patients who underwent surgical intervention were included. There were 3 thoracic and 13 lumbar lesions. All patients presented with intractable back pain at the start of treatment. Six patients had a fever, nine had inflammation at the hemodialysis access site, and six of them had concomitant bacteremia. Ten patients had an elevated leukocyte count. Serological tests indicated an elevation of the C-reactive protein and erythrocyte sedimentation rate level in all patients. Five patients had a neurological compromise. Postoperative complications included two mortalities, two iliac bone graft and implant dislodgement, and one retroperitoneal wound dehiscence. The preoperative mean visual analog scale score was 7.7 (range, 6-9), which improved to 3.4 (range, 2-5) at the final follow-up for 14 surviving patients. Neurological improvement was obtained by at least one grade in four Frankel C category patients. The radiographs revealed a good bony fusion in 12 cases although with a variable bone graft subsidence. In conclusion, early diagnosis of infectious spondylitis is difficult due to latent symptoms. A spine infection should be suspected in hemodialysis patients with severe back pain, even when they are afebrile. Surgical intervention for infectious spondylitis in ESRD patients undergoing hemodialysis can be performed with acceptable outcomes; however, the complication and mortality rates are relative high. PMID- 20585967 TI - The effect of different surface treatments on roughness and bond strength in low fusing ceramics. AB - The aim of this study was to evaluate the influence of different surface treatments (air abrasion, acid etching, and laser irradiation) on the surface roughness and bond strength of a low fusing ceramic. Thirty-six discs of low fusing ceramic (Finesse, Ceramco) were prepared (10 mm in diameter and 2 mm in thickness) according to the manufacturer's instructions. Specimens were divided into three groups (n = 12), and the following treatments were performed: Air abrasion with alumina particles (50 MUm), acid etching with 5% HF and Nd:YAG laser irradiation (distance: 1 mm, 100 mJ, 20 Hz, 2 W, and 141.54 J/cm(2)). Following determination of surface roughness (R(a)) by profilometry, specimens were examined with scanning electron microscopy (SEM). The luting cement (Clearfil Esthetic Cement) was bonded to the ceramic specimens using Teflon tubes. After 24 h of water storage, shear bond strength test was performed using a universal testing machine at a crosshead speed of 1 mm/min. The data were analyzed with two-way analysis of variance (ANOVA) and Tukey HSD tests (alpha = .05). Two-way ANOVA indicated that surface roughness was significantly affected by surface treatments (p < .001). Tukey honestly significant difference (HSD) indicated that the air abrasion group had a significantly higher mean value (p < .05) than the other groups. Shear bond strength was significantly affected by surface treatments (p < .001). Tukey HSD indicated that the air abrasion group had a significantly higher mean value (p < .05) than the other groups. No significant difference was found between the acid-etching and laser-irradiation groups (p > .05). The SEM image of the laser irradiation surface appeared to be relatively smooth as compared to the images of other the groups. Air abrasion of low-fusing porcelain surfaces was effective in improving the bond strength as compared to the acid-etching and laser-irradiation methods. PMID- 20585968 TI - Long-term successful control of super-multidrug-resistant human immunodeficiency virus type 1 infection by a novel combination therapy of raltegravir, etravirine, and boosted-darunavir. AB - Drug-resistant virus infection has been a major hurdle in the management of human immunodeficiency virus type 1 (HIV-1) infection. Recently, three novel antiretrovirals [raltegravir (RAL), etravirine (ETR), and darunavir (DRV)] were introduced into the market almost simultaneously, and salvage regimens containing these three antiretrovirals have been reported to exhibit strong potency against drug-resistant HIV-1 infection. However, the sustainability of such regimens remains unclear, particularly for patients infected with multidrug-resistant viruses. Here we report a case of super-multidrug-resistant HIV-1 infection which has been successfully controlled by novel combination therapy including RAL, ETR, and DRV for over 2 years, indicating that the novel combination could become an ultimate weapon against drug-resistant HIV infection and could alter the landscape of HIV salvage therapy. PMID- 20585969 TI - A randomized comparative study of single-dose fosfomycin and 5-day ciprofloxacin in female patients with uncomplicated lower urinary tract infections. AB - Uncomplicated lower urinary tract infections (UTIs) are the most frequent infections in females. Increased resistance rates against commonly used antibiotics have led to the use of novel antimicrobials. The aim of the present study was to evaluate the bacteriological and clinical effects of single-dose fosfomycin trometamol (FMT) and 5-day ciprofloxacin in females with uncomplicated UTIs. In this randomized comparative study, 260 female patients between 18 and 65 years of age enrolled, of whom 142 completed the study. The most frequently isolated bacterial pathogen in the urine cultures of patients were Escherichia coli (82.3%) and Enterobacter spp. (8.4%). FMT sensitivity was 94% and ciprofloxacin sensitivity was 59% in Escherichia coli; in comparison, FMT sensitivity was 75% and ciprofloxacin sensitivity was 50% in Enterobacter spp. The MIC90 for FMT was 4 MUg/ml. Of the 142 patients, 77 were treated with FMT and 65 were treated with ciprofloxacin. The clinical remission rate was 83% in the FMT group and 81% in the ciprofloxacin group; the bacterial eradication rate was 83% in the FMT group and 78% in the ciprofloxacin group, and there was no significant difference between the two study groups. In conclusion, a single dose of FMT (at 3 g) was as effective as ciprofloxacin, at 500 mg twice a day for 5 days, in the treatment of uncomplicated lower UTIs. It was concluded that the use of FMT as a first-line treatment in the empirical treatment of uncomplicated UTIs might have a positive impact on the problem of resistance to other antibiotics. PMID- 20585970 TI - The evolutionary context for a self-nonself discrimination. AB - This essay was written to illustrate how one might think about the immune system. The formulation of valid theories is the basic component of how-to-think because the reduction of large and complex data sets by the use of logic into a succinct model with predictability and explanatory power, is the only way that we have to arrive at "understanding". Whether it is to achieve effective manipulation of the system or for pure pleasure, "understanding" is a universally agreed upon goal. It is in the nature of science that theories are there to be disproven. An experimentally disproven theory is a successful one. As they fail experimental test one by one, we end up with a default theory, that is, one that has yet to fail. Here, using the self-nonself discrimination as an example, how-to-think as I see it, will be illustrated. PMID- 20585971 TI - Persistence with Chytridiomycosis does not assure survival of direct-developing frogs. AB - The chytrid fungus, Batrachochytrium dendrobatidis (Bd) has been linked to extinction and decline of numerous amphibians. We studied the population-level effects of Bd in two post-decline anuran species, Eleutherodactylus coqui and E. portoricensis, at El Yunque National Forest, Puerto Rico. Data on amphibian abundance was updated to report long-term population trends. Mark-recapture data was used to monitor Bd-infection status and estimate survival probabilities of infected versus uninfected adults. Prevalence of Bd (number of infected/total sampled) and individual infection level (number of zoospores) were compared among age classes at Palo Colorado Forest (661 m) and Elfin Forest (850 m). Results revealed that both species continued to decrease in Palo Colorado Forest, while in the Elfin Forest, E. portoricensis recuperated from drastic declines. Age class, season, and locality significantly predicted zoospore load. Age was also significantly associated with high zoospores loads among Bd-positive frogs, and the prevalence of Bd was higher in juveniles than adults in all populations studied. We suggest that early age represents a critical life stage in the survival of direct-developing frogs infected by this fungus. Survival probability was always higher for uninfected frogs, but recapture rates of infected versus uninfected adults were significantly different only in Palo Colorado, alerting that the negative effect of Bd infection under enzootic conditions is greater at mid-elevations. This work contributes to our understanding of how direct developing amphibians persist with Bd, pointing to critical life stages and synergistic interactions that may induce fluctuations and/or declines in the wild. PMID- 20585972 TI - Persistence of highly pathogenic avian influenza H5N1 virus defined by agro ecological niche. AB - The highly pathogenic avian influenza (HPAI) H5N1 virus has spread across Eurasia and into Africa. Its persistence in a number of countries continues to disrupt poultry production, impairs smallholder livelihoods, and raises the risk a genotype adapted to human-to-human transmission may emerge. While previous studies identified domestic duck reservoirs as a primary risk factor associated with HPAI H5N1 persistence in poultry in Southeast Asia, little is known of such factors in countries with different agro-ecological conditions, and no study has investigated the impact of such conditions on HPAI H5N1 epidemiology at the global scale. This study explores the patterns of HPAI H5N1 persistence worldwide, and for China, Indonesia, and India includes individual provinces that have reported HPAI H5N1 presence during the 2004-2008 period. Multivariate analysis of a set of 14 agricultural, environmental, climatic, and socio-economic factors demonstrates in quantitative terms that a combination of six variables discriminates the areas with human cases and persistence: agricultural population density, duck density, duck by chicken density, chicken density, the product of agricultural population density and chicken output/input ratio, and purchasing power per capita. The analysis identifies five agro-ecological clusters, or niches, representing varying degrees of disease persistence. The agro-ecological distances of all study areas to the medoid of the niche with the greatest number of human cases are used to map HPAI H5N1 risk globally. The results indicate that few countries remain where HPAI H5N1 would likely persist should it be introduced. PMID- 20585973 TI - Incidence of chronic atrophic gastritis: systematic review and meta-analysis of follow-up studies. AB - Chronic atrophic gastritis (CAG) is an important precursor lesion of intestinal gastric cancer. As it is typically asymptomatic, epidemiological data on the incidence of CAG are sparse. We aimed to provide an overview of published data on CAG incidence (overall and according to risk factors) from follow-up studies. Articles with information on incidence of CAG published in English until 26th of July 2009 were identified through a systematic MEDLINE and EMBASE search. Data extracted include study characteristics and key findings regarding the incidence of CAG. A meta-analysis was performed on the association between Helicobacter pylori infection and CAG incidence. Overall, data on CAG incidence were available from 14 studies, in 7 studies incidence could be estimated according to H. pylori infection. Most studies were conducted in symptomatic or high risk populations and the maximum number of incident cases was 284. Incidence estimates ranged from 0 to 11% per year and were consistently below 1% in patients not infected with H. pylori. The highest incidence was observed in a special study conducted on ulcer patients treated by proximal gastric vagotomy. Rate ratios for the association between H. pylori infection and CAG incidence ranged from 2.4 to 7.6 with a summary estimate of 5.0 (95% confidence interval: 3.1-8.3). Incidence of CAG is very low in the absence of H. pylori infection. There is a need for more population-based studies to provide comparable estimates of incidence and the impact of risk factors in the development of CAG. PMID- 20585974 TI - Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study. AB - While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women. PMID- 20585975 TI - Synthesis and spectroscopy of novel branched fluorescent dyes containing benzophenone parts and the possibility as fluorescence probes. AB - This paper describes a new fluorescent family of branched dyes containing benzophenone unit including 4-N, N-diphenylamino-4'-phenacyl-stilbene (C1), 4,4' di(4-benzoylphenylethylene)yl-triphenylamine (C2) and 4,4',4"-tri(4 benzoylphenylethylene)yl-triphenylamine (C3). Benzophenone part is coupled with core through C-C double bond. The chemical structures of the derivatives are characterized with (1)H and (13)C nuclear magnetic resonance and elemental analysis. Strong pi-pi stacking interactions are discovered with the analysis of the X-ray crystallographic data of C1. The absorption maxima and emission maxima of the derivatives exhibit gradual bathochromic shift from C1 to C3. The optical density of C1, C2 and C3 are shown to be related to the number of branches. The changes of dipole moments between the excited and ground states for C1, C2 and C3 were estimated to be 4.356, 8.091 and 8.479 Derby, respectively by Lippert equation, confirming that the internal charge transfer (ICT) dominates the process of excited singlet state. The possibility as fluorescence probes of the derivatives on the estimation of what region of micelles interacting with samples was evaluated. PMID- 20585976 TI - Affective differentiation in breast cancer patients. AB - Fifty-three breast cancer patients completed an Internet-based diary measuring daily negative affect and positive affect and daily negative and positive events for seven consecutive evenings shortly after surgery. The authors used Hierarchical Linear Modeling (Raudenbush and Bryk in Hierarchical linear models: applications and data analysis methods. Sage, Thousand Oaks, CA, 2002) to examine moderators of affective differentiation, or the daily relationship between the patients' negative affect and positive affect. Strong affective differentiation is characterized by the relative independence of negative and positive affect. There were no significant Level 1 (within-subject) moderators of affective differentiation. However, at Level 2 (between-subject), as predicted, increased age was associated with stronger affective differentiation, as was greater use of planning to cope with breast cancer. Also as predicted, increased anxiety and greater use of behavioral disengagement and denial coping were associated with weaker affective differentiation. The results suggest the value of the affective differentiation construct, and a daily diary methodology, for research on the daily lives of breast cancer patients. PMID- 20585977 TI - A new method to efficiently produce transgenic embryos and mice from low-titer lentiviral vectors. AB - Vector injection into the perivitelline space has emerged as the standard delivery method to transduce lentivirus to mammalian oocytes or one-cell embryos, but its application is limited by the need for high titers of lentivirus. Herein we developed a new method by using a Piezo impact micro-manipulator for injecting low titer of lentivirus into the subzonal space of two-cell embryos or the perivitelline space of one-cell embryos that were shrunk with a highly concentrated sucrose solution. The survival rate of embryos was greater than 98% using this micromanipulation strategy, which was increased compared to the normal one-cell embryo injection method. More than 90% of injected embryos were GFP positive after subzonal injection of a lentivirus vector carrying the GFP gene with titers of 2 * 108 I.U./ml. Even when a low titer of lentivirus (2 * 106 I.U./ml) was used, 53.26% and 40.85% transgenic embryos were obtained after two cell embryonic injection and one-cell sucrose treated embryonic injection, respectively. The GFP-positive rates were also greater than in the conventional method of injecting one-cell embryos (25.39%). In addition, blastocysts from the two-cell embryo injection group displayed stronger GFP fluorescence than the one cell embryo injection groups treated with or without the sucrose solution. Increased expression of GFP suggests that the embryos obtained from this injection method have higher exogenous gene expression levels compared to previous methods. Therefore, in contrast with the traditional injection method, we have demonstrated a simplified and efficient lentivirus-mediated gene transfer method based on a low-titer virus preparation. PMID- 20585978 TI - Infection with specific Helicobacter pylori-cag pathogenicity island strains is associated with interleukin-1B gene polymorphisms in Venezuelan chronic gastritis patients. AB - BACKGROUND: The cag pathogenicity island (cag-PAI) is one of the major virulence factors of Helicobacter pylori, showing considerable geographic variation. AIM: We investigated the prevalence of cagA, cagE, and cagT genes of cag-PAI and their association with proinflammatory IL-1B-511/-31/+3954 polymorphisms in Venezuelan chronic gastritis patients from a high-risk gastric cancer region. METHODS: Presence of cag-PAI genes and IL-1B polymorphisms in 121 biopsy specimens was evaluated by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. RESULTS: cagA (+) and triple-positive (cagAET (+)) strains were detected in 79.3% and 70.2% of patients, respectively. We found that infection with cagA (+) and cagAET (+) strains was associated (P < 0.05) with hosts harboring both IL-1B +3954C allele and IL-1B-511T/-31C/+3954C haplotype (TCC (+)). The frequency of gastric atrophy was significantly higher (P < 0.020) among cagAET (+)/IL-1B-TCC (+) combined genotype carriers. CONCLUSION: Carriage of IL-1B +3954C allele and IL-1B-TCC (+) haplotype could favor colonization of bacterial cagAET (+) strains, and the combination of these bacterial and host haplotypes could play a synergistic role in development of premalignant gastric lesions. This work contributes to understanding of the complex interaction between H. pylori virulence factors and cytokine genotypes involved in gastrointestinal diseases. PMID- 20585979 TI - Endoscopic therapy for peptic ulcer hemorrhage: practice variations in a multi center U.S. consortium. AB - BACKGROUND: Peptic ulcer disease is a common cause of acute upper gastrointestinal hemorrhage. The aim of this study was to describe the endoscopic management of bleeding peptic ulcers in a large, U.S. multi-center endoscopic consortium with diverse practice settings. METHODS: Adult patients who underwent upper endoscopy (EGD) for hematemesis, melena or "suspected upper GI bleed" between January 2000 and December 2004 in the Clinical Outcomes Research Initiative (CORI) endoscopic database were screened for the finding of peptic ulcer. The ulcer stigmata, endoscopic therapy and the need for repeat EGD were compared across practice sites. RESULTS: Of 12,392 patients who underwent EGD for an upper gastrointestinal bleeding indication, 3,692 (30%) had at least one peptic ulcer (clean base 59.9%; flat pigmented spot 13.4%; active bleeding 10.7%; clot 7.2%; non-bleeding visible vessel (NBVV) 6.3%). Endoscopic therapy was applied to 93% of actively bleeding ulcers and 95% of NBVV. Repeat endoscopy was required in 7.3% of patients. Ulcers treated with injection monotherapy had the highest repeat EGD rates (12.2%) compared with contact thermal monotherapy (6.1%) and combination thermal/injection therapy (7.1%) (P=0.02). Immediate hemostasis rates were 88-97% across all therapeutic modalities. There was no statistical difference in hemostasis rates across therapy nor practice types. CONCLUSION: In this multi-center consortium, initial hemostasis rates were high across therapy types and sites studied. Injection monotherapy was associated with the highest rates of repeat EGD, supporting guidelines that advise against its use in bleeding peptic ulcers. PMID- 20585980 TI - Enteral access by double-balloon enteroscopy: an alternative method of direct percutaneous endoscopic jejunostomy placement. AB - BACKGROUND: Although direct percutaneous endoscopic jejunal feeding tube placement is an increasingly accepted method of providing small-bowel access for long-term enteral nutrition, it is reliant on push enteroscopy and remains a technically challenging procedure with significant failure rates. Double-balloon enteroscopy, with its ability to provide controlled small-bowel intubation may facilitate direct percutaneous endoscopic jejunal tube placement. AIMS AND METHODS: We report a prospective series of ten consecutive cases of double balloon enteroscopy-assisted direct percutaneous endoscopic jejunal placement, accompanied by a step-by-step illustrated overview of the technique. RESULTS: Direct percutaneous endoscopic jejunal tube placement by double-balloon enteroscopy was successful in nine of the ten attempted cases. In the first case, direct percutaneous endoscopic jejunal placement was abandoned due to inadequate transillumination; there were no procedure-related complications in any of our patients. CONCLUSIONS: This first reported prospective case series of double balloon enteroscopy-assisted direct percutaneous endoscopic jejunal placement shows a promisingly high success rate; larger comparative studies are required to clearly establish any advantages over the originally described push enteroscopy method. PMID- 20585981 TI - Non-invasive index for predicting significant liver fibrosis: comparison of diagnostic performances in patients with chronic hepatitis B and C. AB - BACKGROUND/AIMS: The majority of non-invasive markers of liver fibrosis have been developed in patients with chronic hepatitis C. We aimed to develop a formula for predicting significant fibrosis in patients with chronic viral hepatitis and to compare the usefulness of published models derived from the data obtained from patients with chronic hepatitis C. METHODS: Serum markers and the METAVIR stage of fibrosis in liver biopsy specimens were compared prospectively in patients with chronic hepatitis B and C (estimation set, 367; validation set, 159). RESULTS: In the estimation set, multiple forward stepwise logistic regression analysis identified gamma-glutamyl transpeptidase, haptoglobin, alpha2 macroglobulin, matrix metalloproteinase-2, and tissue inhibitor of metalloproteinase-1 as independent predictors of significant fibrosis. A formula termed the SF index was constructed with the aforementioned five variables. The areas under the receiver operating characteristic curves of the SF index for predicting significant fibrosis were 0.828, 0.776, and 0.827 in the estimation, validation, and total sets, respectively. Using cut-off scores of 2.2 and 3.3, significant fibrosis was predicted with considerable accuracy. The diagnostic performances of the SF index and the Zeng index derived from chronic hepatitis B patients were much better than indices derived from chronic hepatitis C patients, such as the APRI, Forns index, and FIB-4. CONCLUSIONS: We developed a novel formula for predicting significant fibrosis in patients with chronic viral hepatitis. Serum indices from studies in patients with chronic hepatitis C were less accurate in patients with chronic hepatitis B for predicting significant fibrosis. PMID- 20585982 TI - A retrospective study of the safety and efficacy of ERCP in octogenarians. AB - BACKGROUND: Pancreatobiliary disease is increased in elderly patients. Because of significant comorbidities, these patients may be at greater risk of developing complications related to endoscopic retrograde cholangiopantreatography (ERCP). OBJECTIVE: The purpose of this study was to compare the indications, interventions, and complications of ERCP of octogenarians with nonoctogenarians. METHODS: A retrospective review of patient records from a single tertiary care hospital was performed. Adult patients undergoing ERCP were divided into two groups according to age. Group 1 patients were of age < 80 years (N = 391), and group 2 patients were > 80 years of age (N = 102). Indications, therapeutic interventions, use of conscious sedation, duration of procedure and complications were retrieved from the patient records. Main outcome measurements included: indications, therapeutic interventions, use of conscious sedation, duration of procedure and complications. RESULTS: There was an increase in sphincterotomy rates (74 vs 63%; P < 0.05) and stent insertions (48 vs 29%; P < 0.001) in the octogenarian group. In group 1 there were 19 cases (4.9%) of post ERCP pancreatitis who spent 251 hospital days (including 59 ICU days) compared with one case (0.98%) in group 2 who required ten hospital days (P < 0.05) and 0 ICU days. Procedure time for octogenarians was greater than nonoctogenarians (33.1 vs 29.8 min; P < 0.05). Octogenarians required less conscious sedation than nonoctogenarians (midazolam 4.1 vs 5.9 mg; P < 0.05 and fentanyl 45.5 vs 80.4 mcg; P < 0.05). CONCLUSIONS: In octogenarians, ERCP is efficacious and safe. It is associated with a lower rate of hospitalization for pancreatitis. ERCP in octogenarians takes longer, is associated with increased interventions (stent insertion and sphincterotomy) and requires less sedation. PMID- 20585983 TI - Growth of M. avium subspecies paratuberculosis in culture is enhanced by nicotinic acid, nicotinamide, and alpha and beta nicotinamide adenine dinucleotide. AB - BACKGROUND: Without known mechanisms of action, Crohn's disease is exacerbated, and ulcerative colitis is improved, by the use of tobacco. Mycobacterium avium subspecies paratuberculosis (MAP) may be zoonotic. We hypothesized that tobacco components might alter the growth kinetics of MAP, explaining these divergent clinical observations. METHODS: The effect of nicotine, nicotinic acid, nicotinamide and alpha and beta nicotinamide adenine dinucleotide (alpha and beta NAD) were studied on eight strains of three mycobacterial species (MAP, M. avium and M. tb. complex). Data are obtained as "cumulative growth index," (cGI) and presented as "percent increase in cumulative GI" (% + DeltacGI). RESULTS: Nicotinic acid enhances the two human MAP isolates (Dominic; 225% + DeltacGI and UCF-4; 92% + DeltacGI) and M. avium (ATCC 25291; 175% + DeltacGI). Nicotinamide (at 6.4 ug/ml) enhances the human MAP isolates (Dominic; 156% + DeltacGI and UCF 4; 79% + DeltacGI) and M. avium (ATCC 25291; 144% + DeltacGI.) Both alpha and beta NAD enhance Dominic; (135 and 150 % + DeltacGI) and UCF-4; (81 and 79% + DeltacGI). At the doses tested, nicotine has no effect on any strain studied. CONCLUSIONS: We show enhancement of MAP growth by nicotinic acid, one of >=4,000 tobacco-related molecules, its amide, nicotinamide and alpha and beta NAD. Pure nicotine has no enhancing effect at the doses studies. PMID- 20585984 TI - Targeting PI3K/Akt/HSP90 signaling sensitizes gastric cancer cells to deoxycholate-induced apoptosis. AB - BACKGROUND: The heat shock protein 90 (HSP90) plays a crucial role in the stability of several proteins that are essential for cell survival and for malignant transformation. The binding of HSP90 with pro-survival kinase Akt prevents proteosomal degradation of Akt and contributes to the functional stabilization of PI3K/Akt signaling and cell survival. Akt kinase and HSP90 are therefore highly over-expressed in a large panel of cancer cell lines and are present in multi-chaperoning complexes. In this paper, we investigated whether targeting both Akt and HSP90 would inhibit the survival pathway in AGS cells (human gastric mucosal cells), and how Akt/HSP90 inhibition modulates the deoxycholate (DC)-induced apoptosis. METHODS: AGS cells in the presence of Akt inhibitors (LY294002 and wortmannin), or HSP90 inhibitor (geldanamycin, GA) for 30 min or 18 h, respectively, were treated with DC (50 uM). Activation of PI3K/Akt signaling was evaluated by measuring the Akt and PTEN phosphorylation. HSP90, caspase-3 and caspase-9 were detected in whole lysates by Western blot analysis. AGS cells, transiently transfected with Akt siRNA, were treated with DC, and apoptosis was measured by caspase-3 activation. Apoptotic-positive cells were counted according to changes of cell morphology by Hoechst staining and fluorescence microscopy. RESULTS: The intrinsic level of phospho-Akt (pAkt; active form), phospho-PTEN (pPTEN; inactive enzyme) and HSP90 were highly expressed in AGS cells indicating the active PI3K/Akt/HSP90 signaling. Although, deoxycholate at low concentration (50 uM) slightly inhibited the expression of pAkt and cleaved HSP90 to 55 KDa fragment, no significant effect on apoptosis induction, up to 4 h (as assessed by caspase-3 activation) was observed. The higher concentrations of DC (100 uM-300 uM) resulted in progressive inhibition of pAkt, activation of PTEN, and specific cleavage of HSP90 to approximately 45 KDa fragments with significant induction of apoptosis. Although DC (50 uM) had no profound effect on Akt/HSP90 and did not induce apoptosis, it became an inducer of apoptosis when cells were pretreated with LY294002, wortmannin, or geldanamycin. Consistent with these findings, significant activation of apoptosis in response to DC (50 uM) was observed in cells with depleted Akt protein. CONCLUSIONS: These results demonstrate that down-regulation of PI3K/Akt pathway with specific cleavage of HSP90 to 45 KDa modulates the pro-apoptotic effects of DC in gastric cells. They further indicate the importance of stable Akt/HSP90 complex in regulation of survival/death responses. PMID- 20585985 TI - Measuring health literacy among immigrants with a phonetic primary language: a case of Korean American women. AB - While the need for understanding the issue of health literacy among ethnic minority groups with limited English skills is rapidly increasing in the US, it is difficult to find valid and useful health literacy tools for certain linguistic minorities. This study was designed to validate the Korean translation of Rapid Estimate of Adult Literacy in Medicine (REALM) and Test of Functional Health Literacy in Adults-Short form (S-TOFHLA). Korean REALM and S-TOFHLA were administered to 98 Korean American women, together with REALM-English. Participants were first-generation immigrants who were educated in Korea. Both Korean REALM and S-TOFHLA resulted in a negatively-skewed distribution. REALM English yielded well-distributed groups with significant correlations with Korean REALM and S-TOFHLA (Spearman's rho = 0.30, P = 0.003 and 0.22, P = 0.03, respectively). Educational level was significantly correlated with REALM-English and Korean S-TOFHLA (Spearman's rho = 0.39, P = 0.000 and 0.25, P = 0.014), but not with REALM-Korean. The translation of REALM and S-TOFHLA into the Korean language did not lead to a valid assessment of health literacy. A more systematic approach is needed to assess health literacy in immigrants with limited English skills, particularly those with a phonetic primary language. Meanwhile, REALM English could be used as a crude health literacy test for individuals with some English skills. PMID- 20585986 TI - Diagnostic and predictive methods for a Niemann-Pick disease type B patient with ocular involvement. PMID- 20585987 TI - Congenital toxoplasmosis--a report on the Danish neonatal screening programme 1999-2007. AB - OBJECTIVES: This paper reports on the national neonatal screening programme for congenital toxoplasmosis (CT) in Denmark conducted from 1999 to 2007, including background, basis for initiation of screening, methods, results, and finally reasons for the discontinuation of the screening. METHODS: A nationwide screening was conducted at Statens Serum Institut, including >98% newborns, and using filter paper eluates (Guthrie card, PKU card) obtained from newborns 5-10 days old. These were analysed for Toxoplasma gondii-specific antibodies (IgM), and if positive, then IgM (ISAGA). Confirmatory serology was performed on children and their mothers (IgM, IgG, IgA, dye test) where infection was suspected, and children with suspected or confirmed CT initiated a 3-month treatment regimen with pyrimethamine, sulfadiazine and folinic acid supplements. Selective cohorts were followed with regard to developmental and clinical outcome. RESULTS: A total of 100 children were diagnosed with CT in the screening period, and only 2 cases were detected outside of the screening programme. CT prevalence was 1.6 per 10,000 live-born infants. Follow-up studies showed new retinochoroidal lesions in affected children despite treatment. CONCLUSION: Screening was terminated August 2007, after it became apparent that no benefit of treatment could be shown. CT was evaluated using a Danish adaptation of the Uniform Screening Panel (ACMG), showing CT as an unlikely candidate for screening today. Whereas results might be comparable with other low-endemic countries with similar strains of T. gondii, neonatal screening and treatment might offer different results in regions with either high prevalence or different strains of T. gondii. PMID- 20585988 TI - Quality of life, subjective well-being, and religiosity in Muslim college students. AB - BACKGROUND: The majority of published research in quality of life (QOL), subjective well-being (SWB), and religiosity has been carried out on Western populations. The objective of this study was to explore the associations between QOL, SWB, and religiosity in an Arabic, Muslim, and understudied sample. METHODS: A convenience sample of 224 Kuwait University undergraduates was recruited. Their ages ranged from 18 to 28 years. The Arabic version of the World Health Organization QOL scale-Brief (WHOQOL-Bref), along with six self-rating scales of physical health, mental health, happiness, satisfaction with life, religiosity, and strength of religious belief were used. The test-retest reliabilities of all the scales ranged between 0.72 and 0.88, indicating good temporal stability. All the correlations of the scales with criteria were significant and ranged from 0.39 to 0.65 indicating from acceptable to good criterion-related validity. RESULTS: Sex-related differences were significant favoring men in nine out of the 13 scales. All the 66 correlations but two were significant and positive. The principal components analysis followed by varimax orthogonal rotation yielded two factors: "Quality of life and well-being" and "Religiosity". CONCLUSIONS: Based on the significant and positive correlations between QOL, SWB, and religiosity, it was concluded that religiosity may be considered as a salient component of, and a contributing factor to, QOL among this sample of Muslim college students. Therefore, Islamic beliefs and practices may have the potential to be integrated in the psychotherapeutic procedures among Muslim clients. PMID- 20585989 TI - Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization. AB - Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2' position) was approximately 20 times more potent than that of 2 (Z configuration at 2'). These results indicated that the configuration of the 2' double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy. PMID- 20585990 TI - Development of a subject-specific model to predict the forces in the knee ligaments at high flexion angles. AB - Recent clinical evidence has suggested that tasks performed in kneeling or squatting postures place the knee at a higher risk for injury because loads across the knee might overload the ligaments. The objective of this study was to develop a subject-specific model of the knee that is kinematically driven to predict the forces in the major ligaments at high flexion angles. The geometry of the femur, tibia, and fibula and the load-elongation curves representing the structural properties of the ACL, PCL, LCL, and MCL served as inputs to the model, which represented each ligament as a nonlinear elastic spring. To drive the model, kinematic data was obtained while loads were applied to the same cadaveric knee at four flexion angles. The force in each ligament during the recorded kinematic data allowed an optimization procedure to determine the location of the ligament attachment sites on each bone and their reference lengths. The optimization procedure could successfully minimize the differences between the experimental and predicted forces only when the kinematics at 90 degrees , 120 degrees , and 140 degrees of flexion were utilized. This finding suggests that the ligaments at the knee function differently at high-flexion angles compared to low flexion angles and separate models must be used to examine each range of motion. In the future, the novel experimental and computational methodology will be used to construct additional models and additional knee kinematics will be input to help elucidate mechanisms of injury during tasks performed in kneeling or squatting postures. PMID- 20585991 TI - Clinicopathological determinants of survival after hepatic resection of hepatocellular carcinoma in 97 patients--experience from an Australian hepatobiliary unit. AB - BACKGROUND: Identification of clinicopathological determinants that predict for risk of recurrence and overall survival after undergoing potentially curative hepatic resection for hepatocellular carcinoma is a strategy towards personalizing therapy to improve outcome. Through evaluation of a center's experience with treatment of a disease, determinants unique to the treated patient cohort may be identified. METHODS: Ninety-seven patients with hepatocellular carcinoma underwent liver resection. Clinical, treatment, and histopathological variables were collected and evaluated using univariate and multivariate analyses with disease-free survival (DFS) and overall survival (OS) as the endpoints. RESULTS: The median follow-up period of 19 (range, 1 to 188) months from the time of hepatic resection. The median DFS and OS after resection of HCC were 17 and 41 months, respectively. Five-year overall survival rate was 45%. Eight independent factors associated with disease-free and overall survival were identified through a multivariate analysis. Three factors: Child-Pugh score (DFS p = 0.045, OS p = 0.001), histopathological grade (DFS p < 0.001, OS p < 0.001), and histological diagnosis of cirrhosis (DFS p < 0.001, OS p < 0.001) predicted for both disease-free and overall survival. CONCLUSION: Integrating the knowledge of identified prognostic factors into clinical decision making may provide a clinicopathological signature that could identify patients at greatest risk of treatment failure such that novel interventions may be applied to improve the survival outcome. PMID- 20585992 TI - Node yield and node involvement in young colon cancer patients: is there a difference in cancer survival based on age? AB - BACKGROUND: The effect on cancer-specific survival (CSS) from the number of resected nodes (node yield) and the number of nodes involved with colon cancer has not been studied with respect to age. PATIENT AND METHODS: Data from 1992 to 2006 from the Surveillance, Epidemiology and End Results (SEER) registry were analyzed for colon cancer patients undergoing curative resection, comparing younger (< 40; n = 2,642) and older (> or = 40; n = 138,769) patients. RESULTS: The mean number of positive nodes and mean node yield was higher for the younger group. Younger patients were more likely to have metastatic disease and to have a nodal yield of > or = 12 nodes, and were less likely to have node-negative colon cancers (all p < 0.0001). Younger age was associated with a lower risk of death from colon cancer (HR = 0.65; p < 0.0001). No CSS effect was noted with the interaction of age with either node yield or node involvement. Node yield < 12 created a higher risk of cancer-specific death (HR = 1.22; p < 0.0001) regardless of stage. KM plots by stage demonstrated a CSS advantage (p < 0.0001) for younger patients. CONCLUSIONS: Younger patients with colon cancers do not have a worse CSS simply because of their young age, so long as proper oncologic surgical principles are adhered to. PMID- 20585993 TI - Revising the Atlanta classification of acute pancreatitis: festina lente. PMID- 20585994 TI - Are we moving towards a new era in minimally invasive thoracic surgery? PMID- 20585995 TI - True aneurysm of the pancreaticoduodenal arteries: a single institution experience. AB - BACKGROUND: True pancreaticoduodenal artery (PDA) aneurysm is a rare but potentially fatal disease. The aim of this study was to make recommendations for management of true PDA aneurysm. METHODS: True aneurysms of the PDA were diagnosed at our institution between 1996 and 2007 and analyzed retrospectively, for clinical presentation, management, and outcome. RESULTS: Eight patients were admitted to our institution for true aneurysms of the PDA. Five patients had aneurysmal rupture, and three were asymptomatic. In the rupture group, computed tomography (CT) showed the retroperitoneal hematoma around the pancreas and aneurysm, ranging from 5 to 25 mm (median, 12 mm). In the non-rupture group, CT revealed saccular aneurysm, ranging from 10 to 20 mm (median, 16 mm). The celiac axis was occluded in two patients, stenotic in four, and normal in two. Two patients underwent laparotomy, and we finally performed transcatheter arterial embolization in seven. All patients are alive, and there is no evidence of recurrence after median follow-up of 6 years. CONCLUSIONS: We recommend treatment of all true PDA aneurysms at the time of diagnosis. True PDA aneurysm with celiac artery stenosis or occlusion requires precise techniques for embolization to preserve blood flow in the celiac artery territory. PMID- 20585996 TI - Hypothesis: human umbilical cord blood-derived stromal cells promote megakaryocytopoiesis through the influence of SDF-1 and PECAM-1. AB - The development and maturation of megakaryocytes (MKs) is a complex and multistage cellular and biological process. The hematopoietic microenvironment plays an important role in megakaryocytopoiesis regulation. Stromal cells, an important ingredient in the hematopoietic microenvironment, may regulate the development of MKs via the adhesion with MKs and via augmentation of cytokine secretion. Our laboratory has previously isolated a novel population of stromal cells from human umbilical cord blood, called hUCBDSCs. Compared with hBMSCs, the hUCBDSCs express higher levels of stromal cell-derived factor-1 (SDF-1) and increase the colony-forming-unit-megakaryocytes (CFU-MK). Meanwhile, there are reports identified a migration defect in PECAM-1-deficient MKs in response to a gradient of SDF-1. Based on literature searches and our experimental findings, we present a hypothesis that hUCBDSCs, secreting high level of SDF-1, modulated the expression of PECAM-1 of MKs, to regulate the megakaryocyte development. PMID- 20585997 TI - Appendiceal mucinous cystadenocarcinoma with implantation metastasis to the incision scar and cutaneous fistula. AB - INTRODUCTION: Mucinous cystadenocarcinoma of the appendix with invasion of the anterior abdominal wall and cutaneous fistula development is a rare condition. To the best of the authors' knowledge, five such cases have been reported in the medical literature. METHODS AND RESULTS: The patient was a 68-year-old man who presented with a mass growing through the incisional scar and a skin fistula with mucinous discharge 1 year after appendectomy via McBurney's incision. Carcinoembroyonic antigen and carbohydrate antigen 19-9 concentration was elevated. Abdominal computed tomography scan revealed a mass in the cecum with involvement of the abdominal wall. Right hemicolectomy with en bloc abdominal wall implant and skin fistula resection with clear margins was performed. DISCUSSION: The patient received intraperitoneal intra- and postoperative chemotherapy. Gross examination of the specimen showed a mass emerging from the remnant stump of the appendix. The patient showed no relapse 1 year after surgery. Clinical, paraclinical features, and treatment options are discussed with review of the literature. PMID- 20585998 TI - Variation in the vitamin D receptor gene is not associated with risk of colorectal cancer in the Czech Republic. AB - PURPOSE: Increased levels of vitamin D may protect against colorectal cancer (CRC) development and recurrence. Accumulating epidemiologic evidence suggests these effects may be partly mediated by genetic variants of the vitamin D receptor (VDR) proposed to be associated with altered risk of CRC. We wished to determine if common VDR polymorphisms affected CRC risk in the Czech Republic, a homogenous European population with a high CRC incidence rate. METHODS: Frequencies of the common VDR gene polymorphisms rs2238136, rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI) were determined using allele-specific PCR in a case control analysis of a series of 754 CRC patients and 627 patients without malignant disease recruited from centers throughout the Czech Republic. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between these variants and risk of CRC. RESULTS: None of the four polymorphisms tested had any significant effect on CRC risk. No significant differences were observed in susceptibility when the population was stratified by anatomical sub-site, sex, BMI, smoking, alcohol, or presence of polyps. CONCLUSIONS: We conclude that common variation in the VDR gene had little effect on its own on predisposition to sporadic CRC in the Czech population. PMID- 20585999 TI - End-of-life options for patients with advanced heart failure. AB - Heart failure is a progressive disease with significant morbidity and mortality, but prognostication often is difficult. Many of the evidence-based therapies for heart failure provide symptomatic benefit, but may have intolerable side effects for patients with advanced disease. At the end of life, there is evidence of varying strengths for pharmacologic and nonpharmacologic relief of common symptoms like dyspnea, fatigue, pain, and depression. Patients also may benefit from inotropic therapy, ventricular assist devices, and hospice care. It is important for physicians to encourage patients to formulate advance directives, including decisions about do not resuscitate orders and deactivation of implantable cardioverter-defibrillators and ventricular assist devices. PMID- 20586001 TI - Does surfactant type cause a differential proinflammatory response in preterm infants with respiratory distress syndrome? AB - INTRODUCTION: The objective of this study was to compare the pulmonary inflammatory response of premature infants with respiratory distress following instillation of one of two commonly available surfactant preparations. METHODS: This was a prospective, randomized investigation of preterm infants who were less than 30 weeks of gestational age, weighed less than 1 kg at birth, and who qualified to receive surfactant. Infants with multiple congenital anomalies or whose mothers were taking anti-inflammatory medications were ineligible. Tracheal aspirates (TAs) were collected on days 1, 3, 5, and 7 and airway cytokines from TAs were assayed for interleukin (IL)-8 and IL-6. RESULTS: Infants were evenly matched by gestation (26+/-2 days and 26+/-1 days [mean+/-SD], Surfactant A and B, respectively) and birth weight (730+/-141 g and 732+/-167 g). TA cytokine levels were not different between or within groups. Ventilator requirements and clinical outcomes were similar between the two groups. CONCLUSION: The postnatal airway inflammatory response observed in preterm infants is not altered by the instillation of either surfactant preparation. PMID- 20586000 TI - Quality-of-life measurements versus disease activity in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a chronic disease affecting the physical, social, and psychological well-being of patients. Different instruments have been developed to measure health-related quality of life, some of which are SLE specific. Contributors to poor quality of life in patients with SLE include fatigue, fibromyalgia, depression, and cognitive dysfunction. Health-related quality of life is not strongly associated with disease activity or organ damage. The Medical Outcomes Survey Short Form 36 is the most common instrument used to measure quality of life in SLE. PMID- 20586002 TI - Comparison of half and full doses of an MF59-adjuvanted cell culture-derived A/H1N1v vaccine in Japanese children. AB - INTRODUCTION: The substantial pandemic (A/H1N1v) influenza disease burden in children highlights the need for effective vaccination. We report the results of modern cell culture technology, lower doses of antigen, and different doses of MF59(R) adjuvant (Novartis Vaccines, Marburg, Germany), on the immunogenicity and safety profile in a healthy Japanese pediatric population. METHODS: A total of 123 children from 6 months to 19 years of age were randomly assigned in a 1:1 ratio to receive, at 21-day intervals, two doses of either 3.75 microg antigen with 50% of the standard MF59 dose (group A) or 7.5 microg antigen and 100% standard MF59 dose (group B). Antibody levels were measured by hemagglutinin inhibition (HI) and microneutralization assays on day 1 and on days 22 and 43 (3 weeks after the first and second vaccinations, respectively). Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period. RESULTS: At 3 weeks after the first vaccination, seroprotective HI antibodies (titers >or=40) were observed in 56% and 78% of subjects from groups A and B, respectively; 100% in both groups exhibited HI titers >or=40 after the second dose. The reactogenicity profile was acceptable, with local and systemic reactions described as mainly mild to moderate in severity. Five serious adverse events were reported, but none related to the study vaccine. CONCLUSION: One dose of cell culture-derived A/H1N1v vaccine containing 7.5 microg antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children, meeting all three European Union Committee for Medicinal Products for Human Use (EU CHMP) licensure criteria. Two doses of 3.75 microg antigen with 50% of the standard MF59 dose fulfilled these licensure criteria. PMID- 20586003 TI - Advances in esophageal stenting: the evolution of fully covered stents for malignant and benign disease. AB - Self-expanding metal stents have become a leading palliative therapy for dysphagia resulting from esophageal, proximal gastric, and mediastinal cancers. Increasingly, fully covered self-expanding plastic stents and now fully covered metal stents have been used to treat a variety of benign esophageal conditions as well as cancer. Several stent designs are available in the United States and many more internationally. Each design has advantages and limitations. Knowledge of the indications for esophageal stenting and the common side effects associated with different designs allows physicians to choose the best stent for a given condition as well as to anticipate complications such as stent migration or restenosis. Compared with partially covered stents, newer, fully covered metal stents may promote less granulation tissue and subsequent stenosis and may be removable even after several weeks. However, the tradeoff may be more frequent migration. Interest in fully covered metal stents in place of fully covered plastic stents for use in strictures and leaks has also grown, despite the lack of a formal indication for metal stents in benign disease. Unfortunately, rigorous studies of newer stent designs are currently lacking. PMID- 20586006 TI - Estimating blood transfusion requirements in preparation for a major earthquake: the Tehran, Iran study. AB - INTRODUCTION: Tehran, Iran, with a population of approximately seven million people, is at a very high risk for a devastating earthquake. This study aims to estimate the number of units of blood required at the time of such an earthquake. METHODS: To assume the damage of an earthquake in Tehran, the researchers applied the Centre for Earthquake and Environmental Studies of Tehran/Japan International Cooperation Agency (CEST/JICA) fault-activation scenarios, and accordingly estimated the injury-to-death ratio (IDR), hospital admission rate (HAR), and blood transfusion rate (BTR). The data were based on Iran's major earthquakes during last two decades. The following values were considered for the analysis: (1) IDR = 1, 2, and 3; (2) HAR = 0.25 and 0.35; and (3) BTR = 0.05, 0.07, and 0.10. The American Association of Blood Banks' formula was adapted to calculate total required numbers of Type- O red blood cell (RBC) units. Calculations relied on the following assumptions: (1) no change in Tehran's vulnerability from CEST/JICA study time; (2) no functional damage to Tehran Blood Transfusion Post; and (3) standards of blood safety are secure during the disaster responses. Surge capacity was estimated based on the Bam earthquake experience. The maximum, optimum, and minimum blood deficits were calculated accordingly. RESULTS: No deficit was estimated in case of the Mosha fault activation and the optimum scenario of North Tehran fault. The maximum blood deficit was estimated from the activation of the Ray fault, requiring up to 107,293 and 95,127 units for the 0 24 hour and the 24-72 hour periods after the earthquake, respectively. The optimum deficit was estimated up to 46,824 and 16,528 units for 0-24 hour and 24 72 hour period after the earthquake, respectively. CONCLUSIONS: In most Tehran earthquake scenarios, a shortage of blood was estimated to surge the capacity of all blood transfusion posts around the country within first three days, as it might ask for a 2-8 times more than what the system had produced following the Bam earthquake. PMID- 20586007 TI - Future humanitarian crises: challenges for practice, policy, and public health. AB - After more than three decades of preoccupation with wars and internal political conflicts, the humanitarian community has the opportunity to reevaluate what humanitarian crises will dominate both policy and practice in the future. In reality, these crises are already active and some are over the tipping point of recovery. These crises share the common thread of being major public health emergencies which, with a preponderance of excess or indirect mortality and morbidity dominating the consequences, requires new approaches, including unprecedented improvements and alterations in education, training, research, strategic planning, and policy and treaty agendas. Unfortunately, political solutions offered up to date are nation-state centric and miss opportunities to provide what must be global solutions. Public health, redefined as the infrastructure and systems necessary to allow communities, urban settings, and nation-states to provide physical and social protections to their populations has become an essential element of all disciplines from medicine, engineering, law, social sciences, and economics. Public health, which must be recognized as a strategic and security issue should take precedence over politics at every level, not be driven by political motives, and be globally monitored. PMID- 20586008 TI - Haiti disaster tourism--a medical shame. AB - The devastating Haiti earthquake rightly resulted in an outpouring of international aid. Relief teams can be of tremendous value during disasters due to natural hazards. Although nobly motivated to help, all emergency interventions have unintended consequences. In the immediate aftermath of the earthquake, many selfless individuals committed to help, but was this really all in the name of reaching out a helping hand? This case report illustrates that medical disaster tourism is alive and well. PMID- 20586009 TI - Legal issues of humanitarian assistance after the 2007 earthquake in Pisco, Peru. AB - The earthquake that struck the central coast of Peru on 15 August 2007 was a disaster that mobilized international humanitarian assistance to address the needs of the affected people in the regions of Huancavelica, Ica, and Lima. It also was an opportunity to prove the effectiveness of regulations and procedures to facilitate the entry and distribution of donations and medical goods during a major emergency. In the first month after the earthquake, the national government approved new regulations that aimed to reduce waiting time while reducing the number of requisites required by customs. More than 5,500 tons of international donations arrived in Peru in a short period of time. Many donated medicines arrived unsorted, without an international non-proprietary (generic) name on the label, and some medicines did not have any relationship with the diseases that would appear in the aftermath of the event. PMID- 20586010 TI - Editorial comments--legal issues of the humanitarian assistance after the 2007 earthquake in Pisco, Peru. PMID- 20586011 TI - Regulating the helping hand: improving legal preparedness for cross-border disaster medicine. AB - Medical care is a highly regulated field in nearly every country. Therefore, it is not surprising that legal issues regularly arise in cross-border disaster operations that have with the potential to profoundly impact the effectiveness of international assistance. Little attention has been paid to preparing for and addressing these kinds of issues. This paper will report on research by the International Federation of Red Cross and Red Crescent Societies (IFRC) on International Disaster Response Law, and discuss new developments in the international legal framework for addressing these issues. For seven years, the IFRC has studied legal issues in cross-border disaster assistance. Its activities have included several dozen case studies, a global survey of governments and humanitarian stakeholders, and a series of meetings and high-level conferences. The IFRC has found a consistent set of regulatory problems in major disaster relief operations related to the entry and regulation of international relief. These include some issues specific to the health field, such as the regulation of drug donations and the recognition of foreign medical qualifications. To address the gaps in domestic and international regulatory structures, the IFRC spearheaded the development of new international guidelines. The legal risks for international health providers in disaster settings are real and should be better integrated into program planning. Governments must become more proactive in ensuring that legal frameworks are flexible enough to mitigate these problems. PMID- 20586012 TI - A graduate curriculum in emergency public health. AB - The increase in adverse health impacts of disasters has raised awareness of the need for education in the field of emergency public health. In the past, most traditional models of graduate education in schools of public health have not incorporated the theory and practice of disaster public health into their curricula. This paper describes the development of a curriculum in emergency public health within a US masters program in public health, and provides a description of the courses that comprise an area of specialization in the field. The interdisciplinary nature of the faculty, close ties with public health practitioners, and practical applications of the nine courses in this program are highlighted. The curriculum is presented as one model that can be used to meet the educational needs of professionals who will assume the responsibility for planning for and responding to the public health impacts of mass-populations disasters. PMID- 20586013 TI - Editorial comments--a graduate curriculum in emergency public health. PMID- 20586014 TI - Single-Breath-Count Test: an important adjunct in the triaging of patients in a mass-casualty incident due to botulism. AB - Clostridium botulinum toxins, the most poisonous substance known to humankind, are considered to be a [US] Centers for Disease Control and Prevention Category A bioterrorist agent. Despite this concern, little has been published with regard to the tactical aspects of triaging a mass-casualty event involving botulism victims arriving at an emergency department. Because neuromuscular-ventilatory failure is a principal reason for botulism's early morbidity and mortality, using a quick and sensitive test to evaluate this possibility is imperative. The purpose of this article is to propose the adoption of the Single-Breath-Count Test (SBCT). The ease and validity of the use of the SBCT in evaluating complications associated with various neuromuscular disorders make it an attractive adjunct for triage during a mass-casualty incident due to botulism. While education, immune globulin, antitoxin, and invasive airway techniques are well-recognized steps in treating botulism, incorporating a time-honored technique such as the SBCT, will be an important addition to the triage process. PMID- 20586015 TI - Care of children at a large outdoor music festival in the United Kingdom. AB - INTRODUCTION: Limited data exist on the standard of care provided for children at mass gatherings and special events (MGSE). Some studies provide valuable insight into the proportion of pediatric patients that can be expected at various types of MGSEs, but an accurate breakdown of the range of pediatric conditions treated at major events has yet to be produced. Such data are essential for the preparation of MGSEs so that the health and safety of children at such events can be adequately safeguarded. The aim of this study is to examine the care requirements for children at a large, outdoor music festival in the United Kingdom. METHODS: A retrospective review of all patient report forms (PRFs) from a large, outdoor music festival held in Leeds (UK) in 2003. Data were extracted from the PRFs using a standardized proforma and analyzed using an Excel computer program. RESULTS: Pediatric cases contributed approximately 15% to the overall workload at the event. Children presented with a range of conditions that varied from those seen in the adult population. Children were more likely than adults to present for medical attention following crush injuries (OR = 2.536; 95% CI = 1.537-4.187); after a collapse/syncopal episode (OR = 2.687; 95% CI = 1.442 5.007); or complaining of nausea (OR = 3.484; 95% CI = 2.089-5.813). Alcohol/drugs were less likely to be involved in the precipitating cause for medical attention in children compared to adults (OR = 0.477; 95% CI = 0.250 0.912). No critical care incidents involving children were encountered during the event. CONCLUSIONS: Mass gatherings and special events in the UK, such as outdoor music festivals, can involve a large number of children who access medical care for a different range of conditions compared to adults. The care of children at large, outdoor music events should not be overlooked. Event planning in the UK should include measures to ensure that appropriately trained and equipped medical teams are used at music festivals to safeguard the welfare of children who may attend. Further research into this exciting area is required. PMID- 20586016 TI - -PLUS prehospital mass-casualty triage: a strategy for addressing unusual injury mechanisms. AB - INTRODUCTION: Simple Triage and Rapid Treatment (START) and more recently developed prehospital casualty triage algorithms are widely used, in part because they are easy to teach and learn, and can be performed rapidly. Every rapid triage protocol has inherent, significant limitations: (1) no mechanism of injury (MOI) considerations; (2) limited assessment points; and (3) no refinement in truly mass-casualty situations where transport of "minor" or "moderate" patients may be delayed. HYPOTHESIS: When rapid initial triage protocols are utilized, a significant triage deficiency ("under-triage") may occur when "minor" or "moderate" casualties actually are more severely injured than initially triaged. Some MOI produce casualties with subtle or latent (i.e., hidden or delayed) signs and symptoms not considered in the commonly used prehospital triage algorithms. This research did not focus on START or other initial triage screening methods. Instead, it focuses on developing follow-on triage guidance to more specifically prioritize "delayed transport" casualties based upon signs and symptoms related to their MOI. METHODS: Using expert opinion and accepted clinical criteria, triage algorithms were developed to re-evaluate patients triaged to "minor" and "moderate" cohorts. A detailed literature search produced a draft list of relevant signs and symptoms for each selected MOI. The lists then were evaluated by a multi-disciplinary panel of experts via an anonymous, mail-based Delphi method. The input shaped triage algorithms for each selected MOI, which then were subjected to a second stage Delphi process. RESULTS: Consensus was achieved using the Delphi method. The algorithms extend patient assessment beyond the rapid initial triage protocols and incorporate triage criteria specific to each selected injury mechanism or condition: (1) penetrating injuries; (2) unconventional MOI (burns, blast, chemical, radiation); (3) smoke and other inhalation exposure; and (4) injuries with concomitant pregnancy. The full list of triage protocols is designated by the acronym "-PLUS". CONCLUSIONS: "-PLUS" Prehospital Casualty Triage may supplement the strengths of already existing, widely accepted mass-casualty triage strategies. It does not displace START or other rapid initial triage protocols, but in mass-casualty situations with extensive delays in transport, it provides a method to identify under-triage of seriously injured casualties. "-PLUS" also presents a framework for capturing the triage considerations used by experienced medical providers, and so may provide a valuable teaching tool for training future triage professionals. Further research and field assessment is required. PMID- 20586017 TI - Editorial comments: -PLUS prehospital mass-casualty triage: a strategy for addressing unusual injury mechanisms. PMID- 20586018 TI - Triage performance of first-year medical students using a multiple-casualty scenario, paper exercise. AB - INTRODUCTION: Large-scale events may overwhelm the capacity of even the most advanced emergency medical systems. When patient volume outweighs the number of available emergency medical services (EMS) providers, a mass-casualty incident may require the aid of non-medical volunteers. These individuals may be utilized to perform field disaster triage, lessening the burden on EMS personnel. OBJECTIVE: The purpose of this study was to evaluate the accuracy of triage decisions made by newly enrolled first-year medical students after receiving a brief educational intervention. METHODS: A total of 315 first-year medical students from two successive classes participated in START triage training and completed a paper-based triage exercise as part of orientation. This questionnaire consisted of 15 clinical scenarios providing brief but sufficient details for prioritization. Subjects assigned each scenario a triage category of Red, Yellow, Green, or Black, based on the START protocol and were allowed four minutes to complete the exercise. Participants from the Class of 2009 were provided with printed START reference cards, while those from the Class of 2008 were not. Two test types varying in the order of patient age values were created to determine whether patient age was a factor in triage assessment. RESULTS: The mean accuracy score of triage assignment by medical student volunteers after a brief START training session was 64.3%. The overall rate of over-triage was 17.8%, compared to an under-triage rate of 12.6%. There were no significant differences in triage accuracy between subjects with and without printed materials (63.9% vs. 64.6%, p = 0.729) or those completing the age-variant test types (64.4% vs. 64.1%, p = 0.889). CONCLUSIONS: First-year medical students who received brief START training achieved triage accuracy scores similar to those of emergency physicians, registered nurses, and paramedics in previous studies. Observed rates of under and over-triage suggest that a need exists for improving the accuracy of triage decisions made by medical and non-medical personnel. This study did not find that printed materials significantly improved triage accuracy, nor did it find that patient age affected the ability of participants to correctly assign triage categories. Future research might further evaluate disaster triage by non-medical volunteers. PMID- 20586019 TI - Non-invasive carboxyhemoglobin monitoring: screening emergency medical services patients for carbon monoxide exposure. AB - INTRODUCTION: Carbon monoxide (CO) toxicity is a significant health problem. The use of non-invasive pulse CO-oximetry screening in the emergency department has demonstrated that the rapid screening of numerous individuals for CO toxicity is simple and capable of identifying occult cases of CO toxicity. OBJECTIVE: The objective of this study was to extend the use of this handheld device to the prehospital arena, assess carboxyhemoglobin (SpCO) levels in emergency medical services (EMS) patients, and correlate these levels with clinical and demographic data. METHODS: This was a retrospective, observational, chart review of adult patients transported to hospital emergency departments by urban fire department EMS ambulances during a six-week period. Each ambulance used a non-invasive pulse CO-oximeter (Rad-57, Masimo Inc.) to record patients' COHb concentrations (SpCO) along with the standard EMS assessment data. Spearman's Rank Correlation tests and Student's t-tests were used to analyze the data and calculate relationships between SpCO and other variables (age, gender, respiratory rate, heart rate, mean arterial pressure, and oxygen saturation measured by pulse oximetry). RESULTS: A total of 36.4% of the patients transported during the study had SpCO documented. Of the 1,017 adults included in this group, 11 (1.1%) had an SpCO >15%. There was no correlation between SpCO and heart rate, ventilatory rate, mean arterial pressure, and oxygen saturation. CONCLUSIONS: Screening for CO toxicity in the EMS setting is possible, and may aid in the early detection and treatment of CO poisoned patients. PMID- 20586020 TI - Frequent use of emergency medical services by the elderly: a case-control study using paramedic records. AB - OBJECTIVE: To identify the factors that lead to increased use of emergency medical services (EMS) by patients 65 years of age and older in an urban EMS system. METHODS: Retrospective, case-control study of frequent EMS use among elderly patients transported during one year in an urban EMS system. Three distinct groups were examined for transports that took place in 1999: (1) 1-3 transports per year (low use); (2) 4-9 times per year (high use); and (3) those transported 10+ times (very high use). This frequency-use indicator variable is the primary outcome measurement. Predictors included age, gender, preexisting medical diseases, ethnicity, number of medications, number of medical problems, primary physician, psychiatric diagnosis, and homelessness. Analysis of predictors was done using ordinal logistic regression model, and a global test of interaction terms. RESULTS: Male gender, black ethnicity, homelessness, and a variety of types of medical problems were associated with increased use of EMS resources. The strongest single predictor of case status remained homelessness, which was nearly eight times as commonly associated with frequent EMS use than for the controls. The number of medical problems and medications also were significantly associated with EMS use in this patient population. There was a lack of association of alcohol, substance abuse, and psychiatric disorders with EMS use. Patients with asthma who did not have a primary care physician were more likely to use EMS services than were those who had a physician. CONCLUSIONS: This analysis highlights homelessness as being strongly associated with frequent EMS use among the elderly and downplays other associated factors, such as psychiatric disease and substance use. Medical illness severity, particularly asthma when no primary care physician is available, also appears to drive frequent EMS use. Both findings have implications in terms of targeting of public resources; providing housing to medically ill elderly and primary care to asthmatics in particular, may provide dividends not only in terms of social welfare and medical care, but in preventing frequent EMS use by the elderly. PMID- 20586021 TI - Health impacts of floods. AB - INTRODUCTION: Floods are the most common hazard to cause disasters and have led to extensive morbidity and mortality throughout the world. The impact of floods on the human community is related directly to the location and topography of the area, as well as human demographics and characteristics of the built environment. OBJECTIVES: The aim of this study is to identify the health impacts of disasters and the underlying causes of health impacts associated with floods. A conceptual framework is developed that may assist with the development of a rational and comprehensive approach to prevention, mitigation, and management. METHODS: This study involved an extensive literature review that located >500 references, which were analyzed to identify common themes, findings, and expert views. The findings then were distilled into common themes. RESULTS: The health impacts of floods are wide ranging, and depend on a number of factors. However, the health impacts of a particular flood are specific to the particular context. The immediate health impacts of floods include drowning, injuries, hypothermia, and animal bites. Health risks also are associated with the evacuation of patients, loss of health workers, and loss of health infrastructure including essential drugs and supplies. In the medium-term, infected wounds, complications of injury, poisoning, poor mental health, communicable diseases, and starvation are indirect effects of flooding. In the long-term, chronic disease, disability, poor mental health, and poverty-related diseases including malnutrition are the potential legacy. CONCLUSIONS: This article proposes a structured approach to the classification of the health impacts of floods and a conceptual framework that demonstrates the relationships between floods and the direct and indirect health consequences. PMID- 20586022 TI - Lessons learned at World Youth Day: collecting data and using postcards at mass gatherings. AB - INTRODUCTION: World Youth Day (WYD) and its associated activities were held in Sydney, Australia from 15-20 July 2008. The aims of this research were to pilot the use of postcards at mass gatherings and to collect baseline data of how young people (age 16-25 years) identify factors that may affect their health and safety when attending mass gatherings. HYPOTHESIS: The concerns of young people in relation to their health and safety at mass gatherings are poorly understood. It was decided that postcards would be an effective method of data collection in the mobile mass gathering environment. METHODS: The research setting was the Pilgrim Walk at WYD. Participants on this walk were young people. To measure their health and safety concerns, a postcard was developed using a Likert scale to rank their attitudes on a continuum. RESULTS: Young people stated that staying hydrated, having enough to eat, and being safe in a crowd were important to them. They also indicated that they perceived, overcrowding, getting to and from an event, and violent behavior as the greatest risks to their health and safety at a mass gathering. CONCLUSIONS: The problems with postcard distribution at a "mobile" mass gathering have been identified. Even so, results gathered showed that young people were focused on "in the moment" aspects of their health; such as access to food and water. They also had concerns for their safety due to potential overcrowding and/or violent behavior. PMID- 20586023 TI - Pre-Traumatic Vaccination Intervention: can dissociative symptoms be reduced? AB - The Pre-Traumatic Vaccination Intervention (PTV) has been developed in an attempt to help rescue personnel cope with anticipated and non-anticipated disasters, and to prevent trauma-related mental disorders during and after a traumatogenic exposure. Contrary to the generally accepted approach of treating trauma after it has occurred, the PTV has been designed to be administered prior to the potentially traumatic event. Based on empirical findings, the PTV training techniques were designed to prepare the participants for distressful situations. Trainees were gradually exposed to increasingly severe sights using cognitive behavioral techniques along with foreseen situations relating to their profession. Various interventions were aimed at normalizing using personal resources and implementing relaxation techniques. The PTV was administrated as part of the Israeli Defense Forces rescue personnel's and military police training courses. The results of an uncontrolled, preliminary study suggest that the intervention reduced the level of dissociation leading to more awareness to the traumatic event's details, less suffering, lower probability of making mistakes, and increased likelihood of returning to normal functioning. Lower dissociation may suggest a lower probability to be diagnosed with post-traumatic stress disorder among rescue personnel. PMID- 20586024 TI - Epidemiology of disasters in the Republic of Macedonia and the Balkan region: improving public health preparedness. PMID- 20586025 TI - Renal replacement therapy in intensive care units: a survey of nephrological practice in northwest Italy. AB - BACKGROUND: Few reports have addressed how current practice reflects uncertainty as to the optimal management of renal replacement therapy (RRT) in Western countries. Current dialytic practice for 2007 in the northwest of Italy was assessed. METHODS: A total of 24 nephrology and dialysis centers covering all of the RRT provided in the intensive care units (ICUs) in northwest Italy took part in the survey. Consultant nephrologists of each center reported their own activities throughout the year 2007 by an e-mailed questionnaire. RESULTS: RRT for a total of 7,842 days was provided by 24 dialysis centers in 79 ICUs for 1,118 patients. RRT median duration (5.76 days/patient) increased with the increasing number of hospital ICU beds. Of the RRT cases, 69.9% were due to acute kidney injury, 23.6% for continuation of a treatment in chronic dialysis patients and 4.2% for extrarenal indications. More than 90% of the patients were treated with high permeability membranes, at a median target dosage of 35.0 ml/kg per hour in continuous (39.4%) or extended modality (6-14 hours, 38.5%). Unfractionated heparin was the most common anticoagulant used (67.5%, median 500 IU/hour). In patients at high risk of bleeding, RRT without or with heparin at low-dose + saline flushes was the most commonly adopted line of treatment, followed by citrate (18% of days of dialysis). The decision to start RRT was made by nephrologists alone or in collaboration with intensivists, whereas dose prescriptions were given by nephrologists alone. CONCLUSIONS: This survey may represent a useful starting point for further research into changes in RRT practice and the adoption of common, shared protocols. PMID- 20586026 TI - Detection of cytokeratin 19, human mammaglobin, and carcinoembryonic antigen positive circulating tumor cells by three-marker reverse transcription-PCR assay and its relation to clinical outcome in early breast cancer. AB - AIMS: To investigate the diagnostic, predictive, and prognostic value of the detection of circulating tumor cells (CTCs) using a three-marker (CK19, hMAM and CEA) RT-PCR assay in patients with early breast cancer. PATIENTS AND METHODS: Peripheral blood was obtained from 50 patients with early-stage breast cancer before any systemic adjuvant therapy and analyzed for the presence of CK-19, hMAM and CEA mRNA-positive CTCs using an RT-PCR assay. The specificity of the primers used was evaluated in 20 healthy individuals, 24 patients with benign breast disease, and 30 patients with metastatic breast cancer. The detection of CTCs was correlated with clinical outcome. RESULTS: The detection rate of three-marker positive CTCs in the blood of patients with early breast cancer was 54.0%, significantly higher than in patients with benign breast disease and healthy blood donors (p=0.002 and p=0.000, respectively). The three-marker RT-PCR assay had 58.8% sensitivity in the parallel test and 100% specificity for CTC detection in the serial test, which was higher than the sensitivity and specificity of single-marker assays. For early breast cancer, correlation analysis between detection of three-marker-positive CTCs and clinicopathological characteristics indicated that detection of threemarker-positive CTCs was significantly correlated with elevated serum CEA levels (p=0.001). After three years of follow up, 13 of the 27 patients with three-marker-positive CTCs in their blood had relapsed and detection of three-marker-positive CTCs was significantly associated with locoregional recurrence and/or distant metastasis (p=0.002). Detection of three-marker-positive CTCs in peripheral blood was an independent risk factor for reduced median relapse-free interval (p=0.000). CONCLUSION: The three-marker RT PCR assay can enhance the sensitivity and specificity of CTC detection compared to singlemarker assay. Detection of three-marker-positive CTCs was associated with relapse and might have important predictive and prognostic implications in early breast cancer. PMID- 20586027 TI - Prognostic value of membrane type 1 and 2 matrix metalloproteinase expression and gelatinase A activity in bladder cancer. AB - PURPOSE: To analyze the behavior of matrix metalloproteinases (MMPs) in their active state in patients with bladder cancer. METHOD: A retrospective study of 50 patients with localized bladder cancer who underwent tumor resection between June 2006 and June 2007 at the National Cancer Institute in Cairo, Egypt was carried out. Tissue samples were collected and the expression of membrane type 1 (MT1) and type 2 (MT2) MMPs was determined by Western blotting. Gelatinase A (MMP-2) activity was estimated by zymographic analysis in tissue samples of each patient and the values were correlated with clinical tumor stage and lymph node status. RESULT: The behavior of MMP-2 showed statistical significance in 90% of tumor tissues compared with 22% of adjacent normal tissues (p<0.001). MT1-MMP was expressed in 88% of tumor tissues compared with 24% of normal tissues (p<0.001); MT2-MMP was expressed in 74% of tumor tissues compared with 12% of normal tissues (p<0.001). While there was a highly significant association between MMP-2 activity and MT1-MMP expression in tumor tissues (p<0.001), there was a moderately significant association between MMP-2 activity and MT2-MMP expression (p=0.018). The results also revealed an association between MT1-MMP and MT2-MMP expression in tumor tissues (p<0.001). MMP-2 activity and MT2-MMP expression in tumor tissues were statistically associated with high tumor stage (p=0.039 and p=0.014, respectively), while the expression of MT1-MMP showed no association with tumor stage (p=0.139). CONCLUSION: MMP-2 activity is associated with an increase in MT2-MMP expression and with lymph node metastasis. No association was found between MT1-MMP expression and lymph node metastasis. PMID- 20586028 TI - Serum SCCA, Cyfra 21-1, EGFR and Cyclin D1 levels in patients with oral squamous cell carcinoma. AB - OBJECTIVES: To determine the concentrations of SCCA, Cyfra 21-1, EGFR and Cyclin D1 in serum of patients with oral squamous cell carcinoma, and investigate their diagnostic value and their relationship with clinical stage, histological differentiation and lymph node metastasis. METHODS: Seventy hospitalized patients with oral squamous cell carcinoma and 72 healthy individuals were included in the study. Venous blood was collected from all study participants, in the oral carcinoma patients before tumor resection. One week after surgery, venous blood was collected again from 20 patients. Serum marker levels were determined by enzymelinked immunosorbent assay (ELISA). RESULTS: The serum SCCA, EGFR and Cyclin D1 concentrations were significantly higher in patients with oral squamous cell carcinoma than in healthy controls, while there was no significant difference in Cyfra 21-1 levels between patients and controls. The serum SCCA concentration decreased after surgery, but there was no significant difference in the serum Cyfra 21-1, EGFR and Cyclin D1 concentrations before and after surgery. Serum SCCA, Cyfra 21-1, EGFR and Cyclin D1 concentrations were not correlated with clinical stage, histological differentiation and lymph node metastasis. When SCCA, EGFR and Cyclin D1 were measured separately, EGFR had the highest diagnostic sensitivity and accuracy and Cyclin D1 had the highest specificity; when any two of the markers were tested in combination, the combined detection of EGFR and Cyclin D1 had the highest sensitivity, specificity and accuracy. CONCLUSIONS: SCCA, EGFR and Cyclin D1 may prove to be useful tumor markers in oral squamous cell carcinoma. The combined determination of EGFR and Cyclin D1 may be of value in the diagnosis of oral squamous cell carcinoma. Serum SCCA may be used as an adjunct in monitoring treatment response. PMID- 20586029 TI - Analysis of methylation patterns and expression profiles of p14ARF gene in patients with oral squamous cell carcinoma. AB - AIMS: To analyze the promoter methylation profile and mRNA expression of the p14ARF gene in oral squamous cell carcinoma (OSCC). METHODS: Promoter methylation of the p14ARF gene was investigated by methylation-specific polymerase chain reaction in paraffin-embedded tissues from 76 patients with OSCC and 57 oral tissues used as healthy controls. Expression of p14ARF mRNA was also determined using real-time quantitative reverse-transcription PCR. The methylation status and mRNA level profile of the gene and their relationship with clinical data were analyzed. RESULTS: Methylation of the p14ARF gene in OSCC was significantly increased compared to normal control tissues (chi(2) = 16.73, p < 0.0001). The relative expression of p14ARF mRNA in OSCC was not significantly different from that in healthy control samples. CONCLUSION: Promoter methylation of p14ARF may be an important mechanism in OSCC, and its determination may be considered an important tool in the early diagnosis and treatment of OSCC. PMID- 20586031 TI - Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model. AB - The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis. PMID- 20586030 TI - High-throughput screening of chemical exchange saturation transfer MR contrast agents. AB - A new high-throughput MRI method for screening chemical exchange saturation transfer (CEST) agents is demonstrated, allowing simultaneous testing of multiple samples with minimal attention to sample configuration and shimming of the main magnetic field (B(0)). This approach, which is applicable to diamagnetic, paramagnetic and liposome CEST agents, employs a set of inexpensive glass or plastic capillary tubes containing CEST agents put together in a cheap plastic tube holder, without the need for liquid between the tubes to reduce magnetic susceptibility effects. In this setup, a reference image of direct water saturation spectra is acquired in order to map the absolute water frequency for each volume element (voxel) in the sample image, followed by an image of saturation transfer spectra to determine the CEST properties. Even though the field over the total sample is very inhomogeneous due to air-tube interfaces, the shape of the direct saturation spectra is not affected, allowing removal of susceptibility shift effects from the CEST data by using the absolute water frequencies from the reference map. As a result, quantitative information such as the mean CEST intensity for each sample can be extracted for multiple CEST agents at once. As an initial application, we demonstrate rapid screening of a library of 16 polypeptides for their CEST properties, but in principle the number of tubes is limited only by the available signal-noise-ratio, field of view and gradient strength for imaging. PMID- 20586032 TI - Liposome contrast agent for CT-based detection and localization of neoplastic and inflammatory lesions in rabbits: validation with FDG-PET and histology. AB - PURPOSE: This study was aimed at assessing the performance of a liposome-based computed tomography (CT) contrast agent to detect tumor and inflammatory lesions in a rabbit model relative to (18)F-fluorodeoxyglucose- positron emission tomography (FDG-PET). MATERIALS AND METHODS: Nine New Zealand White rabbits were inoculated with a cell suspension obtained from the tumor tissue of a donor rabbit bearing VX2 carcinoma. Spontaneously formed inflammatory lesions were identified in the skeletal muscles of six of the nine animals. The CT liposome agent (185 +/- 37 mg/kg of iodine) was administered intravenously 7 days following tumor inoculation. The PET/CT imaging session took place five days post liposome contrast administration and 1 h post (18)F-FDG injection (30.3 +/- 5.1 MBq/kg). Approximately 20 h post-imaging, the tumor and inflammatory lesions were excised for histo-pathology assessment. RESULTS: Liposome-CT identified the same number of primary tumors as FDG-PET (nine lesions, volumes = 0.07-7.01 cm(3), SUV(max) = 1.5-10.9, HU(mean) = 103.0-140.6). It also detected 25 inflammatory lesions (volumes = 0.01-2.73 cm(3), HU(mean) = 114.5-268.6), while FDG-PET identified seven (volumes = 0.05-1.04 cm(3), SUV(max) = 2.7-7.1). Differences in the mean CT signal (HU(mean)) between the tumor and inflammatory lesions were statistically significant (p < 0.0001). Partial volume adjusted SUV(max) values for the two lesion types calculated from the FDG-PET data set did not yield a significant difference (p > 0.15). CONCLUSION: These results demonstrate that liposome-CT can be considered for effective screening of neoplastic and inflammatory diseases, as well as subsequent image-guided biopsy. Moreover, the differential accumulation of the liposomal agent at tumor and inflammatory sites highlights its potential role in increasing the specificity of image-based diagnosis. PMID- 20586033 TI - Serine- and mannose-modified liposomal contrast agent for computed tomography: evaluation of the enhancement in rabbit liver VX-2 tumor model. AB - Kupffer cell imaging is a powerful tool for the detection of liver cancer. This diagnostic procedure depends on the faculty of the reticuloendothelial system (RES) which takes up foreign bodies, including small particles. The current study aimed to develop a novel RES targeting liposomal contrast agent that functionalized with serine or mannose, the moiety specifically binding to a corresponding receptor on phagocytic cells. Liposomes loaded with non-ionic X-ray contrast media, Iohexol, were prepared by supercritical carbon dioxide reverse phase evaporation method and were intravenously injected to healthy rabbits in order to evaluate the liver parenchymal enhancement in X-ray computed tomography (CT). From 10 to 40 min after injection, the mean enhancement value of the liver parenchyma approached 45 and 34 Hounsfield units (HU) when serine-modified iodinated liposomal contrast agent (ILCA) and mannose-modified ILCA were applied, respectively. The tumor-to-liver contrast values were also evaluated after the administration of the prepared ILCA to rabbits with VX-2 carcinoma. For serine modified ILCA, tumor-to-liver contrast was 82 HU at 1 min and >24 HU at 10-40 min; for mannose-modified ILCA, the values were 58 HU at 0.5 min and >21 HU at 10 40 min. These vales estimated from the region of intrest and the imaging figures of liver indicate the potential of ILCA for clinical use. PMID- 20586034 TI - Development of magnetic chromatography to sort polydisperse nanoparticles in ferrofluids. AB - Whatever the strategy of synthesis, nanoparticles in magnetic fluids commonly feature a broad size distribution. However, the presence of several size populations in ferrofluids is often problematic because of the close relationship between the efficiency of the nanoparticles and their physicochemical properties. In this work, a magnetic size sorting procedure is developed in order to reduce this polydispersity, using the magnetic properties of the iron oxide nanoparticles. This magnetic sorting with an adjustable magnetic field allows isolation of the small superparamagnetic particles as well as the larger particles. Magnetometry, nuclear magnetic relaxation dispersion profiles and transmission electron microscopy were successfully used to check the efficiency of the magnetic sorting procedure, which was shown to work as a 'magnetic' chromatography. PMID- 20586035 TI - Patlak plot analysis CT-GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs. AB - Glomerular filtration rate (GFR) can be determined using Patlak plot analysis with single-slice dynamic computed tomography (CT). Acute autologous graft failure has several causes, all of which induce a measurable decrease in glomerular filtration rate. This study demonstrated in an experimental model of canine autologous renal transplant that CT-derived renal plasma clearance was significantly lower (p = 0.002) in dogs having undergone transplant (0.077 +/- 0.058 ml min(-1) ml renal tissue(-1)) compared with control dogs (0.396 +/- 0.139 ml min(-1) ml renal tissue(-1)). A significant negative curvilinear relationship was seen between serum creatinine and total renal plasma clearance (R(2) = 0.84, p = 0.0001). Alterations in renal time attenuation curve shape in dogs having undergone transplant may have been related to increased renal vascular resistance related to tubular necrosis. CT-GFR may be a useful experimental tool in the evaluation of renal dysfunction in transplant models. PMID- 20586036 TI - Improved synthesis of DOTA tetraamide ligands for lanthanide(III) ions: a tool for increasing the repertoire of potential PARACEST contrast agents for MRI and/or fluorescent sensors. AB - The synthesis of new DOTA tetraamide (DOTAMR(4)) compounds is of great interest given their application in the formation of Ln(III) complexes as potential PARACEST contrast agents in MRI or fluorescent molecular probes. In this context amino acid and peptide DOTAMR(4) derivatives are particularly attractive since the amino-acid and/or peptide moiety can show responsive properties dependent on a given stimuli which might translate to changes in water exchange rates of the corresponding Ln(III) complex. Current synthesis of DOTAMR(4) derivatives is typically carried out by reacting haloacetamide intermediates with cyclen. However, this method fails to generate the tetra-substituted products when bulky substituents are present in the haloacetamide and in some cases this intermediate cannot be prepared by conventional acylation procedures limiting the number of DOTAMR(4) compounds available for study. As a solution to these limitations, an improved methodology for the synthesis of DOTAMR(4) by coupling DOTA to an appropriate amine containing reagent (i.e. protected amino-acids with the alpha amino group free) is presented in this work. Several DOTAMR(4) derivatives which are difficult or impossible to prepare with the traditional methodologies were easily obtained starting with DOTA. A new protocol was derived using this methodology for the solution-phase synthesis of DOTA peptide derivatives. With this methodology, many other DOTAMR(4) peptide and non-peptide derivatives have been prepared in our laboratories with several of these new compounds showing interesting properties for molecular imaging. PMID- 20586037 TI - Parental cancer and the family: a population-based estimate of the number of US cancer survivors residing with their minor children. AB - BACKGROUND: Cancer diagnosis and treatment of a parent has considerable impact on the lives of their minor children, family caregivers, and patients themselves. Understanding the number and characteristics of the population of cancer survivors with children younger than 18 years of age would help to better target services for these survivors and their children and to stimulate and inform research on these understudied families. METHODS: This study identified adults with a history of cancer (n = 13,385) who participated in the United States National Health Interview Survey (NHIS) between 2000 and 2007. The authors examined the prevalence and characteristics of survivors residing with their minor children, both in the total sample and among survivors diagnosed within the last 2 years. RESULTS: Among these adult survivors, 18.3% (95%CI, 16.3-20.5) of those recently diagnosed and 14.0% (95%CI 13.3-14.8) of the total sample reported living with a minor child. Most of these survivors were female (78.9%), married (69.8%), and younger than age 50 years (85.8%). Of the 3193 identified children of survivors, 30.5% were younger than age 6 years at the time of their parent's cancer diagnosis; 33.4% were born after the diagnosis. By using population-based weights, the authors estimated that 1.58 million US cancer survivors reside with their minor children, representing 2.85 million children. Furthermore, an estimated 562,000 US minor children are living with a parent in the early phases of cancer treatment and recovery. CONCLUSIONS: There is a large population of families for whom cancer may pose special challenges and for whom assessment of needs and referral to resources are essential. PMID- 20586038 TI - A population-based estimate of cancer survivors residing with minor children. PMID- 20586039 TI - Exploring the relationship between preterm placental calcification and adverse maternal and fetal outcome. AB - OBJECTIVES: To explore the relationship between preterm placental calcification and adverse pregnancy outcome, including maternal and fetal outcomes. METHODS: In this prospective cohort study, monthly ultrasonography was performed starting at 28 weeks' gestation to establish the diagnosis of Grade III placental calcification. Women were classified into three groups: Group 1, the early preterm group, with placental calcification found prior to 32 weeks (n = 63); Group 2, the late preterm group, with placental calcification found between 32 and 36 weeks (n = 192); and Group 3, the control group, without placental calcification noted between 28 and 36 weeks (n = 521). Women who smoked cigarettes or drank alcohol during pregnancy, or who had hypertension, diabetes, significant antenatal anemia or placenta previa were all excluded. Logistic regression analysis was used to estimate the risks of adverse pregnancy outcome in Groups 1 and 2 by calculating odds ratios (OR) with 95% CIs, adjusted by maternal age, body mass index, economic status, marital status, type of delivery and parity. RESULTS: Risks for adverse maternal outcome including postpartum hemorrhage (OR, 3.43; 95% CI, 1.251-9.388), placental abruption (OR, 6.52; 95% CI, 1.356-31.382) and maternal transfer to the intensive care unit (OR, 9.76; 95% CI, 1.826-52.195) and for adverse fetal outcomes including preterm birth (OR, 4.20; 95% CI, 1.775-9.940), low birth weight (OR, 4.58; 95% CI, 2.201-9.522), low Apgar score (OR, 6.53; 95% CI, 2.116-20.142) and neonatal death (OR, 9.04; 95% CI, 1.722-47.411) were much higher in Group 1 than in Group 3. In contrast, there were no significant differences in adverse pregnancy outcome between Groups 2 and 3. CONCLUSIONS: Early preterm placental calcification is associated with a higher incidence of adverse pregnancy outcome, and may serve as an indicator of adverse maternal and fetal outcomes when noted on ultrasonography. Conversely, women with late preterm placental calcification are not at greater risk for adverse pregnancy outcome. PMID- 20586040 TI - Enlarged parietal foramina: findings on prenatal ultrasound and magnetic resonance imaging. PMID- 20586041 TI - Added value of the gray-scale whirlpool sign in the diagnosis of adnexal torsion. AB - OBJECTIVE: Adnexal torsion is a common gynecologic emergency affecting females of all ages. Expedient diagnosis and treatment are important, particularly in young fertile patients to preserve ovarian viability. Classical parameters for the clinical and sonographic diagnosis of adnexal torsion have very high false positive rates, approaching 50%. The sonographic 'whirlpool' sign has been shown to be effective for visualizing the torsed part in the prenatal diagnosis of malrotation of the midgut with volvulus, as well as scrotal and ovarian torsion. We aimed to evaluate the efficacy of the whirlpool sign in the diagnosis of torsion, as compared to a protocol based on 'classic' sonographic signs of torsion alone. METHODS: This was a retrospective chart review. Files of all patients who underwent laparoscopy for suspected torsion at our center between January 2006 and May 2009 were extracted and reviewed. Ultrasound reports were retrieved from our computerized database. Patients were assigned to the study group if the whirlpool sign had been investigated during pre-procedural evaluation or to the control group if only the standard protocol had been applied. RESULTS: Eighty women were referred for laparoscopy for suspected adnexal torsion during the study period. In 22 women the ultrasound investigation had included the whirlpool sign (study group) while 58 had been examined by the standard protocol (control group). Twenty women in the study group had a positive whirlpool sign on ultrasound, 18 of whom (90.0%) had confirmed torsion on laparoscopy. In the control group 32 of 58 (55.2%) women had confirmed torsion on laparoscopy. CONCLUSION: The addition of the sonographic whirlpool sign to the preoperative sonographic evaluation of patients with suspected torsion appears to improve the rate of true-positive diagnoses as confirmed by laparoscopy. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd. PMID- 20586043 TI - Longitudinal reference ranges for umbilical vein blood flow at a free loop of the umbilical cord. AB - OBJECTIVE: To establish longitudinal reference ranges for the umbilical vein (UV) diameter, velocities and volume blood flow (Q(uv)) at a free loop of the umbilical cord and estimate the UV spatial velocity profile at this site. METHODS: This was a prospective study of 53 low-risk pregnancies. The UV diameter and blood flow velocities were measured at 4-weekly intervals from 22 + 0 to 39 + 6 weeks of gestation (232 observations) using B-mode ultrasonography and pulsed wave Doppler. Multilevel regression modeling was used to estimate the reference percentiles. RESULTS: The mean UV diameter, velocities and Q(uv) increased with advancing gestation, whereas the Q(uv) normalized for estimated fetal weight decreased. The UV spatial velocity profile coefficient was 0.62. CONCLUSION: We have established reference ranges for serial measurements of Q(uv) at a free loop of the umbilical cord during the second half of pregnancy. The spatial velocity profile of the UV is not completely parabolic at this site. PMID- 20586046 TI - On-chip manipulation of protein-coated magnetic beads via domain-wall conduits. PMID- 20586051 TI - Mind the gap: it's not as robust as you thought...: Can recent insights into RNA based epigenetics, a reassessment of network robustness and a revival of Waddington's epigenetic landscape illuminate the environmental component of disease? PMID- 20586053 TI - Speciation and the neutral theory of biodiversity: Modes of speciation affect patterns of biodiversity in neutral communities. AB - The neutral theory of biodiversity purports that patterns in the distribution and abundance of species do not depend on adaptive differences between species (i.e. niche differentiation) but solely on random fluctuations in population size ("ecological drift"), along with dispersal and speciation. In this framework, the ultimate driver of biodiversity is speciation. However, the original neutral theory made strongly simplifying assumptions about the mechanisms of speciation, which has led to some clearly unrealistic predictions. In response, several recent studies have combined neutral community models with more elaborate speciation models. These efforts have alleviated some of the problems of the earlier approaches, while confirming the general ability of neutral theory to predict empirical patterns of biodiversity. However, the models also show that the mode of speciation can have a strong impact on relative species abundances. Future work should compare these results to diversity patterns arising from non neutral modes of speciation, such as adaptive radiations. PMID- 20586056 TI - Albumin nanoshell encapsulation of near-infrared-excitable rare-Earth nanoparticles enhances biocompatibility and enables targeted cell imaging. AB - The use of traditional fluorophores for in vivo imaging applications is limited by poor quantum yield, poor tissue penetration of the excitation light, and excessive tissue autofluorescence, while the use of inorganic fluorescent particles that offer a high quantum yield is frequently limited due to particle toxicity. Rare-earth-doped nanoparticles that utilize near-infrared upconversion overcome the optical limitations of traditional fluorophores, but are not typically suitable for biological application due to their insolubility in aqueous solution, lack of functional surface groups for conjugation of biomolecules, and potential cytotoxicity. A new approach to establish highly biocompatible and biologically targetable nanoshell complexes of luminescent rare earth-doped NaYF(4) nanoparticles (REs) excitable with 920-980 nm near-infrared light for biomedical imaging applications is reported. The approach involves the encapsulation of NaYF(4) nanoparticles doped with Yb and Er within human serum albumin nanoshells to create water-dispersible, biologically functionalizable composite particles. These particles exhibit narrow size distributions around 200 nm and are stable in aqueous solution for over 4 weeks. The albumin shell confers cytoprotection and significantly enhances the biocompatibility of REs even at concentrations above 200 microg REs mL(-1). Composite particles conjugated with cyclic arginine-glycine-aspartic acid (cRGD) specifically target both human glioblastoma cell lines and melanoma cells expressing alpha(v)beta(3) integrin receptors. These findings highlight the promise of albumin-encapsulated rare earth nanoparticles for imaging cancer cells in vitro and the potential for targeted imaging of disease sites in vivo. PMID- 20586057 TI - Single-cell-level cancer therapy using a hollow optical fiber-based microplasma. PMID- 20586054 TI - Vasa genes: emerging roles in the germ line and in multipotent cells. AB - Sexually reproducing metazoans establish a cell lineage during development that is ultimately dedicated to gamete production. Work in a variety of animals suggests that a group of conserved molecular determinants act in this germ line maintenance and function. The most universal of these genes are Vasa and Vasa like DEAD-box RNA helicase genes. However, recent evidence indicates that Vasa genes also function in other cell types, distinct from the germ line. Here we evaluate our current understanding of Vasa function and its regulation during development, addressing Vasa's emerging role in multipotent cells. We also explore the evolutionary diversification of the N-terminal domain of this gene and how this impacts the association of Vasa with nuage-like perinuclear structures. PMID- 20586058 TI - Direct CdTe quantum-dot-based fluorescence imaging of human serum proteins. PMID- 20586059 TI - Expression and characterization of a fusion protein-containing cyclodextrin glycosyltransferase from Paenibacillus sp. A11. AB - A recombinant cyclodextrin glycosyltransferase (CGTase) gene fused with thioredoxin (Trx), hexa-histidine (His(6)) and S-protein (S) at the N terminus and a proline-rich peptide (PRP) at the C terminus, was constructed using the wild-type gene from Paenibacillus sp. A11, the pET-32a vector and Escherichia coli BL21(DE3) as the host cell. The expression levels and enzyme characteristics of the Trx-His(6)-CGTase-PRP fusion protein, the recombinant CGTase without fusion peptides, and the wild-type CGTase were compared. The maximum specific activity for the Trx-His(6)-CGTase-PRP fusion enzyme was 2.7 fold higher than that of the non-fusion form at the optimal IPTG concentration. The Trx-His(6) CGTase-PRP fusion protein was purified to homogeneity by starch adsorption and Ni NTA affinity chromatography, with a specific activity of 2,268 units/mg protein at a 61% yield. The ease of purification and the higher enzyme yield were obtained with the fusion form when compared to the non-fusion and wild-type enzymes. The fusion enzyme was superior than its wild-type counterpart in terms of stability against high temperature and organic solvents. Moreover, the fusion enzyme could catalyze the synthesis of cyclodextrins in 20% (v/v) dimethylformamide with a higher product yield of CD(7) and CD(8) compared to that of the wild-type enzyme in the same buffer-solvent system. PMID- 20586060 TI - Simultaneous determination of quinolones in fish by liquid chromatography coupled with fluorescence detection: comparison of sub-2 microm particles and conventional C18 columns. AB - A simple and effective multi-residue analysis method is presented for the extraction and determination of eleven quinolones (pipemidic acid, enoxacin, norfloxacin, ciprofloxacin, lomefloxacin, enrofloxacin, gatifloxacin, difloxacin, oxolinic acid, nalidixic acid and flumequine) in fish tissues. In this study, multi-residue separations on four columns packed with 5 microm or sub-2 microm particles were simultaneously developed for the purpose of comparison. Various gradients were optimized and best resolutions were achieved on each column. A short and sub-2 microm particle-sized HPLC column was chosen for its advantages in analysis time and column performance. Additionally, considering the matrix effect of the complex crude fish tissue, an effective extraction protocol was also established for sample pre-treatment procedure. Good recoveries (71-98%) were obtained from samples fortified with a mix of eleven quinolones at three levels, with satisfactory relative standard deviations and limits of detection. As a result, the sub-2 microm HPLC column and proposed analytical procedures have been evaluated and applied to the analysis of different fish tissues. Detectable residues were observed in 8 of 30 samples, at concentrations ranging from 4.74 to 23.27 microg/kg. PMID- 20586061 TI - Sodium selenate effect on Synechococcus elongatus PCC 7942: appearance of novel enzymatic reaction, ATP:selenate adenylyltransferase, and variation in antioxidant enzyme activities. AB - Synechococcus elongatus PCC 7942 was grown with SO(4) (2-) or S(2)O(3) (2-) sulfur source with varying concentration of SeO(4) (2-). Up to 150 muM, SeO(4) (2 ) was growth supportive and above this it was inhibitory. Selenate is believed to induce ROS production, and to counter, the cells produce increasing amounts of ROS quenching enzymes. To investigate the differential growth response of SeO(4) (2-) at the level of ROS production, the activities of antioxidant enzymes viz. glutathione peroxidase, catalase, pyrogallol-peroxidase, superoxide dismutase and glutathione reductase were determined. Regardless of SeO(4) (2-) concentration in the medium, except catalase, the activity of other enzymes increased over SeO(4) (2-)-free controls. To understand the fate of SeO(4) (2-) added at lower concentrations, the activities of key inorganic sulfur metabolizing enzymes, ATP sulfurylase in SO(4) (2-) medium and thiosulfate reductase in S(2)O(3) (2-) medium were measured. This was done with an assumption that these enzymes would consume the SO(4) (2-) analog SeO(4) (2-) as sulfur source. We found enzymatic SeO(4) (2-)/ATP dependent formation of inorganic pyrophosphate in a reaction, analogous to ATP sulfurylase (SO(4) (2-) + ATP --> pyrophosphate) carried out by an enzyme different from ATP sulfurylase, tentatively called ATP:selenate adenylyltransferase. We hypothesize that selenium could act as trace element for S. elongatus PCC 7942. PMID- 20586062 TI - Hyper-production of alpha-amylase from agro-residual medium with high-glucose in SSF using catabolite derepressed Bacillus subtilis KCC103. AB - In Bacillus subtilis KCC103, alpha-amylase is hyper-produced and alpha-amylase synthesis is not subject to catabolite repression. The alpha-amylase was produced from KCC103 by solid-state fermentation (SSF) using agro-residues and oil cakes as growth substrates. The KCC103 was also tested for its resistance to repression by hyper level (>10% w/w) of glucose and xylose on alpha-amylase production in SSF. Among growth media containing various combinations of agro-residues, the medium with wheat bran and sunflower oil cake supported highest enzyme production (20700 IU (g dry wt)(-1)). The alpha-amylase production was enhanced (4.2 folds) by optimizing the growth substrate and the process parameters: the optimal conditions were wheat bran:sun flower oil cake ratio-1:1 (w/w), substrate particle size-500 mum, substrate to flask volume-1:100 (w/v), initial substrate moisture content-90% (v/w), inoculum size-35%, initial medium pH-7.0, growth temperature-37 degrees C and cultivation time-48 h. alpha-Amylase production was further enhanced up to 1.7 folds when SSF was carried out using optimized medium supplemented with sugars or yeast extract (1% w/v) under optimized conditions. Supplementation of biomass sugars, glucose or xylose at 20% (w/w), did not repress the synthesis of alpha-amylase showing the hyper-tolerance of KCC103 to repression by simple sugars on alpha-amylase production in SSF. PMID- 20586063 TI - Mutational studies of the peptidoglycan hydrolase FlgJ of Sphingomonas sp. strain A1. AB - The flagellar protein FlgJ, a member of glycoside hydrolase family 73, has N- and C-terminal domains that are responsible for flagellar rod assembly and peptidoglycan hydrolysis, respectively. The crystal structure of the C-terminal domain of SPH1045 (SPH1045-C), the FlgJ from Sphingomonas sp. strain A1, showed a long cleft formed by two lobes, alpha and beta. In this study, seven site specific mutants of residues in the cleft were prepared and analyzed. Enzyme activity was reduced most significantly in mutants E185A and Y281A, followed by E224A. A comparison of the crystal structure of the inactive mutant E185A with that of other related enzymes revealed that Glu185 is structurally reasonable as the proton donor and that Tyr281 is close to Glu185. Glu224 is, however, far from the catalytic site, which is inconsistent with the decreased activity exhibited by E224A. The structural flexibility of Glu224 and its neighboring residues observed in SPH1045-C may indicate that this region is able to change its conformation upon substrate binding. PMID- 20586064 TI - Effect of different stresses on trehalose levels in Rhizopus oryzae. AB - Rhizopus oryzae accumulates and degrades trehalose in response to environmental stress conditions such as heat, osmotic stress, nitrogen starvation and pH. When heat stress was applied to R. oryzae, the trehalose content of the cells was increased from 0.9 to 4.8 mg/g dw and when the stress was relieved it decreased back to 1.1 mg/g dw. Under osmotic stress and nitrogen starvation, trehalose content was increased by 3.5 and 3 fold, respectively. The decrease in external pH increased trehalose level up to 2.6 mg/g dw from 1.1 mg/g dw. Increased trehalose level decreased back to normal after pH stress was relieved. These results indicate that trehalose accumulates and acts as a stress protectant in R. oryzae. PMID- 20586065 TI - Triplex PCR-based detection of enterotoxigenic Bacillus cereus ATCC 14579 in nonfat dry milk. AB - Although many strains of Bacillaceae are considered nonpathogenic, Bacillus cereus is recognized worldwide as a bacterial pathogen in a variety of foods. The ability of B. cereus to cause gastroenteritis following ingestion of contaminated food is due to the production of enterotoxins. The ubiquity of this genus makes it a persistent problem for quality assurance in food processing environments. The primary objective of this study was to develop and apply a multiplex real time PCR-based assay for rapid and sensitive detection of enterotoxigenic B. cereus. Template DNA was separately extracted from tryptic soy broth (TSB)-grown and 2.5% Nonfat Dry Milk (NFDM)-grown B. cereus using a commercial system. Three enterotoxin gene fragments (hblC, nheA, and hblA) were simultaneously amplified in real-time followed by melting curve analysis to confirm amplicon identity. Resolution of melting curves (characteristic T(m)) was achieved for each amplicon (hblC = 74.5 degrees C; nheA = 78 degrees C; and hblA = 85.5 degrees C in TSB and 84 degrees C in NFDM) with an assay sensitivities of 10(1) CFU/ml for both TSB and NFDM-grown B. cereus compared to 10(4) CFU/ml in either matrix using gel electrophoresis. The results demonstrate the potential sensitivity of real-time bacterial detection methods in a heterogenous food matrix using real-time PCR. PMID- 20586066 TI - A developed DNA extraction method for different soil samples. AB - Four DNA extraction methods namely SDS-hyperhaline method (I), modified SDS hyperhaline method (II), indirect method (III), alkaline lysis method (IV) were evaluated by comparing DNA yield, spectrophotometric quality, genomic integrity and PCR suitability in this paper. The results showed that high DNA yields were obtained by method I, II and IV. However, higher quality of DNA was gained by method III and IV. Based on the results of the Pulsed-Field Gel Electrophoresis (PFGE), the completeness of DNA extracted by method IV was the best. About 6.0 microg DNA can be recovered from 1.0 g soil by method IV which involved to lysis cell by SDS and to precipitate impurities by adding potassium acetate and magnesium chloride Therefore, it is confirmed that method IV is a novel, reliable and versatile method for large-scale DNA extraction involving less purification steps for various soil samples. PMID- 20586067 TI - Characterization of an extracellular alkaline lipase from Pseudomonas mendocina M 37. AB - A strain of Pseudomonas mendocina producing extracellular lipase was isolated from soil. The bacterium accumulates lipase in culture fluid when grown aerobically at 30 degrees C for 24 h in a medium composed of olive oil (1%) as substrate. Pseudomonas mendocina lipase was optimally active at pH 9.0, temperature of 50 degrees C and was found to be stable between pH 7.0-11.0. The lipase was inhibited by detergents such as SDS and Tween-80. The enzyme was stable in various organic solvents tested with maximum stability in chloroform followed by toluene and exhibited 1-3 regiospecificity for hydrolytic reaction. This lipase was capable of hydrolyzing a variety of lipidic substrates and is mainly active towards synthetic triglycerides and fatty acid esters that possess a butyryl group. Metal ions like Mg(2+), Ca(2+) and Na(+) stimulated lipase activity, whereas, Cu(2+), Mn(2+) and Hg(2+) ions caused inhibition. PMID- 20586068 TI - Production of laccase from Pleurotus florida using agro-wastes and efficient decolorization of Reactive blue 198. AB - Pleurotus florida NCIM 1243 produced laccase as the dominant lignolytic enzyme during the dye decolorization. Banana peel was the best substrate for extracellular laccase production under solid state fermentation when compared to mandarin peel and cantaloupe peel. The maximum activity of laccase (5.4 U/g) was detected on the 10 day. The ratio of banana peel: mandarin peel: cantaloupe peel (5:2:3) showed increased production of laccase (6.8 U/g). P. florida produced two extracellular laccase isoenzymes (L1 and L2). The half life of laccase at 60 degrees C was 2 h and at 4 h it retained 25% residual activity. P. florida laccase showed high thermostability and an interesting difference was noticed in the behavior of laccase isoenzymes at different temperature. The L1 isoenzyme of laccase showed remarked thermostability at 60 degrees C in the native PAGE when compared to L2 isoenzyme. The optimum pH, temperature and enzyme concentration for maximum decolorization was found to be 4.5, 60 degrees C and 1.2 U/ml, respectively. Partially purified laccase enzyme showed excellent decolorization activity to Reactive blue 198. The maximum decolorization (96%) was observed at lower dye concentrations (50-100 ppm) which decreased markedly when the dye concentration was increased beyond 150 ppm. The thermostable laccase of P. florida could be effectively used to decolorize the synthetic dyes in the textile effluent and other biotechnological applications. PMID- 20586069 TI - Thermotolerance of germlings and mycelium of the insect-pathogenic fungus Metarhizium spp. and mycelial recovery after heat stress. AB - The upper temperature limits for germination and growth were determined for Metarhizium acridum (ARSEF 324, 3341 and 3609), M. robertsii (ARSEF 2575), M. anisopliae (ARSEF 5749), and Aspergillus nidulans (ATCC 10074). Most of the Metarhizium species germinated well at 35 and 36 degrees C; however, compared to 28 degrees C, the growth was very slow (except ARSEF 5749 from Mexico, which germinated at 35 degrees C, but did not grow at 34 or 36 degrees C). Germination was severely impaired at 38 and 40 degrees C for all Metarhizium species. ARSEF 324 conidia were the most thermotolerant. Based on radial growth measurements, however, none of the M. anisopliae or M. robertsii isolates grew (produced visible colonies) during 10 days at 38 degrees C. All Metarhizium species kept at 38 and 40 degrees C for 10 days resumed growth when transferred to 28 degrees C, and they all sporulated. When the plates were held 10 days at 42 degrees C, however, only the two M. acridum isolates (ARSEF 324 and 3609) grew after returning to 28 degrees C, but with some delay. Conidia germinated at restrictive temperatures, but the growth was impaired or discontinued soon after germination. Nevertheless, when transferred to a permissive temperature, they produced colonies and new conidia. In contrast, the thermophilic A. nidulans germinated and grew well at 42 degrees C, and therefore was much more thermotolerant than any of the Metarhizium spp. isolates. PMID- 20586070 TI - The role of diamondback moth cuticle surface compounds in pre-penetration growth of the entomopathogen Isaria fumosoroseus. AB - Transcript patterns elicited in response to hosts can reveal how fungi recognize suitable hosts and the mechanisms involved in pathogenicity. These patterns could be fashioned by recognition of host-specific topographical features or by chemical components displayed or released by the host. We investigated this in three isolates of Isaria fumosoroseus which has shown considerable pathogenic ability against Plutella xylostella. Conidia inoculated to hind wings had the highest germination ability while the conidia inoculated to head regions showed the lowest germination. Conidia applied to diamondback moth wings showed slightly lower rates of germination than those incubated on SDA. Although I. funosoroseus isolates germinated well on crude methanol extracts, only low levels of germination occurred on hexane and dichloromethane extracts. Similarly, poor germination was also observed on diamondback moth hind wing from which cuticular lipids were extracted by using methanol when compared to the untreated hind wings showing that simple polar compounds are required to stimulate germination before the fungus can make effective use of a complex mixture of non-polar lipids. Such studies could address the origin of intraspecies differences and correlate these differences with the underlying metabolic and biosynthetic differences that define different host ranges. PMID- 20586071 TI - Microcalorimetric investigation of the toxic action of berberine on Tetrahymena thermophila BF(5). AB - Tetrahymena thermophila (T. thermophila) BF(5) produces heat through growth and metabolism. By microcalorimetry, the power-time curves of the metabolism of T. thermophila BF(5) at 28 degrees C were measured and some quantitative parameters were obtained from these curves. Then the action of berberine on this microbe was investigated. Furthermore, the minimum inhibitory concentration (MIC) of berberine against T. thermophila BF(5) growth was obtained by tube dilution method. Berberine of different concentrations had various actions on T. thermophila BF(5) growth: a low concentration (25 MUg/ml) of berberine began to inhibit the growth of T. thermophila BF(5) and a high concentration (450 MUg/ml) of berberine completely inhibited T. thermophila BF(5) growth. The toxic action of berberine could also be expressed as half-inhibitory concentration IC(50), i.e., 50% effective in this inhibition. The value of IC(50) was 175.60 MUg/ml, while the MIC of this compound against T. thermophila BF(5) was 20.76 mg/ml. Berberine has strong toxic action on T. thermophila BF(5) growth. The microcalorimetric method for the assay of toxic action is quantitative, inexpensive and versatile. PMID- 20586072 TI - Bacteriophage analysis of staphylokinase-negative Staphylococcus aureus strains isolated from people. AB - Staphylokinase is one of virulence factors produced by Staphylococcus aureus strains. Producing it is associated with the presence of prophage in a bacterial cell which carries the sak gene. In this study, we examined the ability to produce staphylokinase by 257 S. aureus strains isolated from the inpatient and the outpatients (carriers) and the fact whether there is a correlation between sensitivity to bacteriophages and the lack of producing staphylokinase by strains. The results of this study showed, that staphylokinase-negative strains of S.aureus are widely common inpatients and among outpatients and their percentage does not usually exceed 20% of staphylococci. All staphylokinase negative S. aureus strains were negative for sak gene. The correlations between a type of clinical material and the frequency of occurrence of staphylokinase negative strains has not been stated. Typing with the use of the basic set of phages has shown that these strains do not constitute a homogenous group and they belong to different phage types. The same phage patterns occur both in staphylokinase-negative strains and in staphylokinase-positive strains, and the differences in phage types have the quantitative character. S.aureus not producing staphylokinase are more frequently common in the phage group II than other phage groups (p < 0.0001) and are typed mainly by 3C and 55 phages. Staphylokinase-negative strains of S. aureus do not occur among the phage group II of strains sensitive to phage 71. PMID- 20586073 TI - Temporal bacterial diversity and detection of putative methanotrophs in surface mats of Lonar crater lake. AB - The phylogenetic diversity of bacterial communities in microbial mats of two different seasons from saline and hyperalkaline Lonar Lake was investigated using 16S rRNA gene library analysis. Arthrospira (Cyanobacteria) related clones (>80% of total clones) dominated libraries of both the seasons. Clear differences were found in both the seasons as the operational taxonomic units (OTUs) related to Fusibacter (LAI-1 and LAI-59) and Tindallia magadiensis (LAI-27) found in post monsoon were not found in the pre-monsoon library. Likewise, OTUs related to Planococcus rifietensis (LAII-67), Bordetella hinzii (LAII-2) and Methylobacterium variabile (LAII-25) found in the pre-monsoon were not found in post-monsoon. The study was extended to identify methanotrophs in the surface mats. Libraries constructed with type I and type II methanotroph specific 16S rRNA gene primers showed the presence of clones (LAMI-99 and LAMII-2) closely related to Methylomicrobium buryaticum and Beijerinckiaceae family members. Denaturing gradient gel electrophoresis (DGGE) fingerprinting based on protein coding genes (pmoA and mxaF) further confirmed the detection of Methylomicrobium sp. Hence, we report here for the first time the detection of putative methanotrophs in surface mats of Lonar Lake. The finding of clones related to organisms with interesting functional attributes such as assimilation of C(1) compounds (LAII-25, LAMI-39, LAMI-99 and LAMII-2), non-sulfur photosynthetic bacteria (LAMII-43) and clones distantly affiliated to organisms of heavily polluted environments (LAI-59 and LAMII-52), is of significant note. These preliminary results would direct future studies on the functional dynamics of microbial mat associated food web chain in the extreme environment. PMID- 20586074 TI - Mating-type orthologous genes in the primarily homothallic Moniliophthora perniciosa, the causal agent of Witches' Broom Disease in cacao. AB - The cacao-pathogenic Moniliophthora perniciosa C-biotype is a primarily homothallic Agaricomycete of which the genome has recently become available. Searching of the genome sequence with mating type proteins from other basidiomycetes detected one or possibly two potential genes for HD1 homeodomain transcription factors, 7 or possibly 8 genes for potential pheromone receptors and five genes for putative pheromone precursors. Apparently, the fungus possesses gene functions encoded in the tetrapolar basidiomycetes in the A and B mating loci, respectively. In the tetrapolar species, the A and B mating type genes govern formation of clamp cells at hyphal septa of the dikaryon and their fusion with sub-apical cells as well as mushroom production. The C-biotype forms fused clamp cells and also basidiocarps on mycelia germinated from basidiospores and their development might be controlled by the detected genes. It represents the first example of a primarily homothallic basidiomycete where A - and B mating-type-like genes were found. Various strategies are discussed as how self compatibility in presence of such genes can evolve. An A -mating-type like gene for an HD2 homeodomain transcription factor is, however, not included in the available sequence representing estimated 69% coverage of the haploid genome but there are non-mating genes for other homeodomain transcription factors of currently unknown function that are conserved in basidiomycetes and also various ascomycetes. PMID- 20586075 TI - Surface hydrophobicity, nutritional contents affect Staphylococcus aureus biofilms and temperature influences its survival in preformed biofilms. AB - The present study investigates the effect of surface hydrophobicity and media on in vitro biofilm formation potential of S. aureus isolates from two dairies. There was lack of correlation between biofilm formation potential of S. aureus and sampling points but not with the source of isolation. Biofilm formation was more pronounced on hydrophobic polypropylene (PP) than hydrophilic stainless steel (SSC). A better correlation was established between the biofilms on SSC and PP when analyzed by crystal violet staining than conventional plating method. On comparative evaluation of nutrient rich and diluted growth media, enhanced biofilm formation was observed in latter (1/20 tryptic soya broth). Highest survival in the preformed biofilms was observed at incubation temperature of 25 degrees C in sterilized skim milk rather than TSB. The present study signify preferable adherence of S. aureus on hydrophobic surfaces and potential survival within preformed biofilm at temperatures prevalent in dairy industries. PMID- 20586076 TI - Thromboelastographic study of biomaterials. AB - Thromboelastography (TEG) is drawing more attention for clinical and in vitro studies of blood coagulation. It can be applied to evaluate the effects of both blood-soluble and insoluble biomaterials on whole blood coagulation from the beginning of coagulation through clot formation to the ending with fibrinolysis. TEG may also identify the relative contributions of various clotting factors, such as fibrinogen and platelets, to the overall coagulation process based on profiles of its variables using whole and partial blood components. A comprehensive review has been conducted on its applications for the assessment of a wide range of blood-contacting biomaterials ranging from polymers to ceramics and biomedical devices involved in many applications. The methodology is different in terms of instrumentation, the methods to activate blood coagulation, the type of blood (citrated versus fresh blood), and study settings (in vitro, in vivo, and clinical trials). The author's own work and future directions are discussed as well. TEG should be considered as one of the most useful tools for evaluating in vitro and in vivo blood-biomaterial interactions for different applications. PMID- 20586077 TI - Corrosion behavior of nitinol in blood serum and PBS containing amino acids. AB - The susceptibility to localized corrosion of metallic, implant medical devices is typically evaluated in a simulated physiological solution, such as phosphate buffered saline (PBS). For implant devices in contact with blood, the underlying premise is that proteins and other components in blood do not significantly change the corrosion susceptibility. This study examined the corrosion behavior of nitinol in bovine serum and PBS containing amino acids (cysteine, glutamine, and tryptophan). Tests were performed on mechanically polished (MP) and black oxide (BO) nitinol wire using cyclic potentiodynamic polarization and electrochemical impedance spectroscopy. They showed that the susceptibility to pitting corrosion of MP nitinol in PBS can be influenced by the presence of amino acids, depending on the type of amino acid. However, the pitting susceptibility of MP and BO nitinol did not differ significantly (based on a t-test, with p < 0.05 being statistically significant) between serum and PBS, suggesting that the combination of proteins and amino acids in serum had little effect. The impedance spectra showed near-capacitive behavior in serum and in PBS alone and with amino acids, and the data could be fitted by a parallel resistance-capacitance (as a constant phase element) circuit associated with the passive oxide film. The capacitance indicated that serum proteins were adsorbed on nitinol but that little, if any, adsorption of the three amino acids under study occurred at the corrosion potential. There did not appear to be a correlation between breakdown and the adsorption of organic compounds in serum. PMID- 20586078 TI - Characterization of viability and proliferation of alginate-poly-L-lysine alginate encapsulated myoblasts using flow cytometry. AB - Genetically modified cells encapsulated in alginate-poly-L-lysine-alginate (APA) are being developed to deliver therapeutic products to treat a variety of diseases. The characterization of the encapsulated cells thus becomes paramount. This study reports a novel method to assess the viability, granularity and proliferation of encapsulated cells based on flow cytometry. The in vitro viability of encapsulated G8 murine myoblasts secreting canine FVIII (cFVIII) measured by flow cytometry was comparable to the traditional trypan blue exclusion method and both correlated with cFVIII secretion levels. In contrast, after implantation into mice, only viability measured by flow cytometry correlated with cFVIII secretion. Further, flow cytometry analysis of encapsulated cells maintained in vitro and in vivo revealed a greater fraction of granular cells compared to free cells, suggesting that encapsulation influences the morphology (cytoplasmic composition) of cells within APA microcapsules. Interestingly, the proliferation study showed that encapsulated cells proliferate faster, on average, and were more heterogeneous in vivo compared to in vitro culture conditions, suggesting that encapsulated cell proliferation is complex and environment-dependent. In conclusion, we show that flow cytometry analysis allows for a more consistent and comprehensive examination of encapsulated cells to aid in the development of cell therapy protocols. PMID- 20586079 TI - Analysis in vitro of the cytotoxicity of potential implant materials. I: Zirconia titania sintered ceramics. AB - Zirconia (ZrO2) is a bioinert, strong, and tough ceramic, while titania (TiO2) is bioactive but has poor mechanical properties. It is expected that ZrO2-TiO2 mixed ceramics incorporate the individual properties of both ceramics, so that this material would exhibit better biological properties. Thus, the objective of this study was to compare the biocompatibility properties of ZrO2-TiO2 mixed ceramics. Sintered ceramics pellets, obtained from powders of TiO2, ZrO2, and three different ZrO2-TiO2 mixed oxides were used. Roughnesses, X-ray diffraction, microstructure through SEM, hardness, and DRIFT characterizations were performed. For biocompatibility analysis cultured FMM1 fibroblasts were plated on the top of disks and counted in SEM micrographs 1 and 2 days later. Data were compared by ANOVA complemented by Tukey's test. All samples presented high densities and similar microstructure. The H2O content in the mixed ceramics was more evident than in pure ceramics. The number of fibroblasts attached to the disks increased significantly independently of the experimental group. The cell growth on the top of the ZrO2-TiO2 samples was similar and significantly higher than those of TiO2 and ZrO2 samples. Our in vitro experiments showed that the ZrO2-TiO2 sintered ceramics are biocompatible allowing faster cell growth than pure oxides ceramics. The improvement of hardness is proportional to the ZrO2 content. Thus, the ZrO2 TiO2 sintered ceramics could be considered as potential implant material. PMID- 20586080 TI - Wear pattern observations from TDR retrievals using autoregistration of voxel data. AB - Because of their unique geometry, characterization of wear damage in total disc replacement (TDR) is difficult. In the article, we developed and validated an automated damage calculation technique for explanted TDR components. Eight polyethylene cores implanted from 4.6 to 16.0 years were using cone-beam microCT imaging (SCANCO Medical, Switzerland). The nominal uniform voxel size for the implant under investigation was 18 mum, however with a smaller sample size increased resolutions (10-microm nominal voxel size) could be achieved using the same microCT imaging hardware. Nominal surface data for both sizes of TDR components we examined were obtained from manufacturer's drawings (Link, Germany) and converted to highly discretized triangular meshes. The damage calculation technique utilized an initial alignment phase, followed by a pointwise calculation of the linear damage at each 3D surface point. During the alignment phase, a three-dimensional surface of the undamaged component was automatically aligned with volumetric image data from the damaged component. The alignment algorithm maximized the contact area between undamaged portions of the implant and its nominal surface using an iterative optimization technique. Linear damage at each triangle on the nominal surface was computed by moving along the local normal of the surface both inward and outward direction for a distance much less than the size of the implant. For the retrieved components, the maximum damage occurred away from the central axis of the dome close to the rim. Penetrations of up to 0.8 mm were observed in this region. Lower magnitude penetrations were observed near the pole of the dome. In conclusion, we have developed an analytical method to automatically align and measure three-dimensional surface damage with both high resolution and accuracy on implants with complicated, nonparametric, surface geometry and used this technique to analyze eight implants. PMID- 20586081 TI - The distinguishing features of human metapneumovirus and respiratory syncytial virus. AB - Acute respiratory tract infections (RTIs) are a leading cause of morbidity and mortality worldwide. Human Metapneumovirus (hMPV) is a member of the Metapneumovirus genus within the Pneumovirinae subfamily of the Paramyxoviridae family. Though hMPV was only discovered in 2001, a large body of work has already shown that it is the aetiologic agent of a substantial proportion of upper and lower RTIs across all age groups in both healthy and immunocompromised hosts throughout the world. RSV, also a pneumovirus, is the human pathogen most closely related to hMPV. RSV is the leading cause of pneumonia and bronchiolitis in infants and young children, but can also cause respiratory tract disease in all age groups. In this paper, we will review the salient features of the virology, epidemiology, pathogenesis, host immune responses, clinical manifestations and diagnostic modalities of hMPV, using RSV as a comparison. In addition, we will show how immunoprophylactic and therapeutic strategies studied and used in clinical practice for RSV-some with great success, and others tragic failure-have led to promising areas of research for the prevention and treatment of the significant burden of disease caused by hMPV. PMID- 20586082 TI - The expanding range of parvoviruses which infect humans. AB - The first human parvoviruses to be described (1960s) were the adeno-associated viruses (AAVs, now classed as dependoviruses), originally identified as contaminants of cell cultures, followed by parvovirus B19 (B19V) in 1974, the first parvovirus to be definitively shown to be pathogenic. More recently two new groups of parvoviruses, the human bocaviruses (HuBoV) and the Parv4 viruses have been identified. These four groups of human viruses are all members of different genera within the Parvovirus family, and have very different biology, epidemiology and disease associations from each other. This review will provide an overview of the virological, pathogenic and clinical features of the different human paroviruses, and how these new viruses and their variants fit into the current understanding of parvovirus infection. PMID- 20586083 TI - Nuclear magnetic resonance water relaxation time changes in bananas during ripening: a new mechanism. AB - BACKGROUND: Nuclear magnetic resonance studies of banana fragments during ripening show an increase on the water transverse relaxation time (T2) and a decrease in water self-diffusion coefficient (D). As T(2) and D are normally directly correlated, we studied these two properties in intact bananas during ripening, in an attempt to rule out the effect of injury on the apparent discrepancies in the behavior of T(2) and D. RESULTS: The results show that injury in bananas causes a decrease in T2 of the water in vacuoles (T(2vac)). They also show that T(2vac) increased and D decreased during ripening, ruling out the injury effect. To explain the apparent discrepancies, we propose a new hypothesis for the increase in T2 values, based on the reduction of Fe3+ ions to Fe2+ by galacturonic acid, produced by the hydrolysis of pectin and a decrease in internal oxygen concentration during ripening. CONCLUSION: As injury alters T2 values it is necessary to use intact bananas to study relaxation times during ripening. The novel interpretation for the increase in T(2vac) based on reduction of Fe+3 and O2 concentration is an alternative mechanism to that based on the hydrolysis of starch in amyloplasts. PMID- 20586084 TI - Walnut (Juglans regia L.): genetic resources, chemistry, by-products. AB - Walnut (Juglans regia L.) is the most widespread tree nut in the world. There is a great diversity of genotypes differing in forestry, productivity, physical and chemical nut traits. Some of them have been evaluated as promising and may serve as germplasm sources for breeding. The nutritional importance of the nut is related to the seed (kernel). It is a nutrient-dense food mainly owing to its oil content (up to 740 g kg(-1) in some commercial varieties), which can be extracted easily by screw pressing and consumed without refining. Walnut oil composition is dominated largely by unsaturated fatty acids (mainly linoleic together with lesser amounts of oleic and linolenic acids). Minor components of walnut oil include tocopherols, phospholipids, sphingolipids, sterols, hydrocarbons and volatile compounds. Phenolic compounds, present at high levels in the seed coat but poorly extracted with the oil, have been extensively characterised and found to possess strong antioxidant properties. The oil extraction residue is rich in proteins (unusually high in arginine, glutamic and aspartic acids) and has been employed in the formulation of various functional food products. This review describes current scientific knowledge concerning walnut genetic resources and composition as well as by-product obtainment and characteristics. PMID- 20586085 TI - Bis(allyl)ruthenium(IV) complexes containing water-soluble phosphane ligands: synthesis, structure, and application as catalysts in the selective hydration of organonitriles into amides. AB - The novel mononuclear ruthenium(IV) complexes [RuCl(2)(eta(3):eta(3) C(10)H(16))(L)] [L=(meta-sulfonatophenyl)diphenylphosphane sodium salt (TPPMS) (2a), 1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3, 7)]decane (PTA) (2b), 1-benzyl 3,5-diaza-1-azonia-7-phosphatricyclo[3.3.1.1(3, 7)]decane chloride (PTA-Bn) (2c), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) (2d), and 2,4,10 trimethyl-1,2,4,5,7,10-hexaaza-3-phosphatricyclo[3.3.1.1(3, 7)]decane (THPA) (2e)] have been synthesized by treatment of the dimeric precursor [{RuCl(mu Cl)(eta(3):eta(3)-C(10)H(16))}(2)] (C(10)H(16)=2,7-dimethylocta-2,6-diene-1,8 diyl) (1) with two equivalents of the corresponding water-soluble phosphane. Reaction of 1 with one equivalent of the cage-type diphosphane ligand 2,3,5,6,7,8 hexamethyl-2,3,5,6,7,8-hexaaza-1,4-diphosphabicyclo[2.2.2]octane (THDP) allowed also the high-yield preparation of the dinuclear derivative [{RuCl(2)(eta(3):eta(3)-C(10)H(16))}(2)(mu-THDP)] (2f). All these new complexes have been analytically and spectroscopically (IR and multinuclear NMR) characterized. In addition, the structure of 2b, 2c, 2d, and 2f was unequivocally confirmed by X-ray diffraction methods. Complexes 2a-f are active catalysts for the selective hydration of nitriles to amides in pure aqueous medium under neutral conditions. The wide scope of this catalytic transformation has been evaluated by using the most active catalysts [RuCl(2)(eta(3):eta(3) C(10)H(16))(THPA)] (2e) and [{RuCl(2)(eta(3):eta(3)-C(10)H(16))}(2)(mu-THDP)] (2f). Advantages of using MW versus conventional thermal heating are also discussed. PMID- 20586086 TI - The catalytic Z to E isomerization of stilbenes in a photosensitizing porous coordination network. PMID- 20586087 TI - Artificial genetic systems: self-avoiding DNA in PCR and multiplexed PCR. PMID- 20586088 TI - Selective and flexible transformation of biomass-derived platform chemicals by a multifunctional catalytic system. PMID- 20586089 TI - An enantioselective total synthesis of (+)-peloruside A. PMID- 20586090 TI - Electronic tuning of nickel-based bis(dicarbollide) redox shuttles in dye sensitized solar cells. PMID- 20586091 TI - The molecular mechanism of spider-silk formation. PMID- 20586092 TI - High-surface-area carbon molecular sieves for selective CO(2) adsorption. AB - A series of carbon molecular sieves (CMSs) has been prepared, either as powders or monoliths, from petroleum pitch using potassium hydroxide as the activating agent. The CMS monoliths are prepared without the use of a binder based on the self-sintering ability of the mesophase pitch. Characterization results show that these CMSs combine a large apparent surface area (up to ca. 3100 m(2) g(-1)) together with a well-developed narrow microporosity (V(n) up to ca. 1.4 cm(3) g( 1)). The materials exhibit high adsorption capacities for CO(2) at 1 bar and 273 K (up to ca. 380 mg CO(2) g sorbent(-1)). To our knowledge, this is the best result obtained for CO(2) adsorption using carbon-based materials. Furthermore, although the CO(2) adsorption capacity for activated carbons has usually been considered lower than that of zeolites, the reported values exceed the total amount adsorbed on traditional 13X and 5A zeolites (ca. 230 mg and 180 mg CO(2) g sorbent(-1), respectively), under identical experimental conditions. Additionally, the narrow pore openings found in the CMS samples (ca. 0.4 nm) allows for the selective adsorption of CO(2) from molecules of similar dimensions (e.g., CH(4) and N(2)). PMID- 20586093 TI - A technique to perfuse cadavers that extends the useful life of fresh tissues: the Duke experience. AB - The demand for laboratory-based teaching and training is increasing worldwide as medical training and education confront the pressures of shorter training time and rising costs. This article presents a cost-effective perfusion technique that extends the useful life of fresh tissue. Refrigerated cadavers are preserved in their natural state for up to 45 days with a daily working period of ten hours. Tissues maintain their color and natural consistency throughout this period. This new process for preservation of tissue opens the door to improved surgical training and to numerous research opportunities. PMID- 20586094 TI - A response to "Pulling my gut out--Simple tools for engaging students in gross anatomy lectures". PMID- 20586096 TI - Acidic hyaluronidase activity is present in mouse sperm and is reduced in the absence of SPAM1: evidence for a role for hyaluronidase 3 in mouse and human sperm. AB - The molecular mechanisms underlying sperm penetration of the physical barriers surrounding the oocyte have not been completely delineated. Although neutral active or "reproductive" hyaluronidases (hyases), exemplified by Sperm Adhesion Molecule 1 (SPAM1), are thought to be responsible for hyaluronan digestion in the egg vestments and for sperm-zona binding, their roles in mouse sperm have been recently questioned. Here we report that acidic "somatic" Hyaluronidase 3 (HYAL3), a homolog of SPAM1 with 74.6% structural similarity, exists in two isoforms in human ( approximately 47 and approximately 55 kDa) and mouse ( approximately 44 and approximately 47 kDa) sperm, where it resides on the plasma membrane over the head and midpiece. Mouse isoforms are differentially distributed in the soluble (SAP), membrane (MBP), and acrosome-reacted (AR) fraction where they are most abundant. Comparisons of zymography of Hyal3 null and wild-type (WT) AR and MBP fractions show significant HYAL3 activity at pH 3 and 4, and less at pH 7. At pH 4, a second acid-active hyase band at approximately 57 kDa is present in the AR fraction. HYAL3 activity was confirmed using immunoprecipitated HYAL3 and spectrophotometry. In total proteins, hyase activity was higher at pH 6 than at 4, where Spam1 nulls had significantly (P < 0.01) diminished activity implicating an acidic optima for murine SPAM1. Although fully fertile, Hyal3 null sperm showed delayed cumulus penetration and reduced acrosomal exocytosis. HYAL3 is expressed in epididymal tissue/fluid, from where it is acquired by caudal mouse sperm in vitro. Our results reveal concerted activity of both neutral- and acid-active hyaluronidases in sperm. PMID- 20586097 TI - H2O2-induced up-regulation of CatSper3 in mouse brain. PMID- 20586098 TI - Dynamic roles of ion currents in early development. AB - Excitable cells have the capacity to modify their electrical properties in response to different stimuli. This specific feature is due to a flux of ion currents that flow via ion channels in the plasma membrane. In all species so far studied, ion channels are proteins expressed in the zygote and in the blastomeres of the developing embryo, and their activity is subject to dynamic changes throughout the early cleavage stages. Although these complex patterns imply that ion currents play a role in signal transduction and the control of embryogenesis, a specific developmental function for the appearance, loss, and alterations of the channels remains to be elucidated. This review reports several aspects surrounding the involvement of ion currents in early embryo development, from invertebrates to human. It focuses on the occurrence, modulation, and dynamic role of ion fluxes through external, intra- and inter-cellular ion channels from the zygote up to the blastula and pre-implantation stages. The implications for a role of ion currents in development, and their possible clinical and technological applications are discussed. PMID- 20586099 TI - The role of endothelial nitric oxide synthase (eNOS) T-786C, G894T, and 4a/b gene polymorphisms in the risk of idiopathic male infertility. AB - A considerable number of infertile men have no known mechanism for their infertility. This study aims to examine if there is an association between endothelial nitric oxide synthase (eNOS) T-786C, G894T, and 4a/b gene polymorphisms and idiopathic male infertility. Three hundred fifty-two men with idiopathic infertility (mean age 32.4 +/- 11.4 years) and 356 healthy controls (mean age 33.2 +/- 11.6 years) with documented fertility were recruited in this study. Genotypes for T-786C, G894T, and 4a/b gene polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) analysis. The eNOS -786CC genotype (0.310 vs. 0.081; odds ratio (OR), 3.64; 95% confidence interval (CI), 2.28-4.46; P = 0.001), 894TT genotype (0.131 vs. 0.006; OR, 3.62; 95% CI, 2.68-4.87; P = 0.001) and 4aa genotype (0.128 vs. 0.009; OR, 2.82; 95% CI, 1.88-3.89; P = 0.004) were significantly more frequent in infertile subjects. Furthermore, there was a significant difference between the group of infertile patients with azoospermia and oligoasthenoteratozoospermia (OAT) when compared by genotype distribution (-786CC vs. 786TT, 894TT vs. 894GG, and 4aa vs. 4bb) (all P < 0.01). We also found an association between the eNOS " 786C," "894T," and "a" alleles and an increased risk of poor semen parameters. Our data revealed a significant relationship between eNOS genotypes and the phenotype of infertility. PMID- 20586100 TI - Surrogate end-points for treatment trials of hepatitis B virus. PMID- 20586101 TI - The interaction of Jagged-1 cytoplasmic tail with afadin PDZ domain is local, folding-independent, and tuned by phosphorylation. AB - Jagged-1, one of the five Notch ligands in man, is a membrane-spanning protein made of a large extracellular region and a 125-residue cytoplasmic tail bearing a C-terminal PDZ recognition motif ((1213) RMEYIV(1218) ). Binding of Jagged-1 intracellular region to the PDZ domain of afadin, a protein located at cell-cell adherens junctions, couples Notch signaling with the adhesion system and the cytoskeleton. Using NMR chemical shift perturbation and surface plasmon resonance, we studied the interaction between the PDZ domain of afadin (AF6_PDZ) and a series of polypeptides comprising the PDZ-binding motif. Chemical shift mapping of AF6_PDZ upon binding of ligands of different length (6, 24, and 133 residues) showed that the interaction is strictly local and involves only the binding groove in the PDZ. The recombinant protein corresponding to the entire intracellular region of Jagged-1, J1_ic, is mainly disordered in solution, and chemical shift mapping of J1_ic in the presence of AF6_PDZ showed that binding is not coupled to folding. Binding studies on a series of 24-residue peptides phosphorylated at different positions showed that phosphorylation of the tyrosine at position -2 of the PDZ-binding motif decreases its affinity for AF6_PDZ, and may play a role in the modulation of this interaction. Finally, we show that the R1213Q mutation located in the PDZ-binding motif and associated with extrahepatic biliary atresia increases the affinity for AF6_PDZ, suggesting that this syndrome may arise from an imbalance in the coupling of Notch signaling to the cytoskeleton. PMID- 20586102 TI - Temperature- and pressure-dependent study of 35Cl NQR frequency and spin lattice relaxation time in 2,3-dichloroanisole. AB - The temperature and pressure dependence of (35)Cl NQR frequency and spin lattice relaxation time (T(1)) were investigated in 2,3-dichloroanisole. Two NQR signals were observed throughout the temperature and pressure range studied. T(1) were measured in the temperature range from 77 to 300 K and from atmospheric pressure to 5 kbar. Relaxation was found to be due to the torsional motion of the molecule and also reorientation of motion of the CH(3) group. T(1) versus temperature data were analyzed on the basis of Woessner and Gutowsky model, and the activation energy for the reorientation of the CH(3) group was estimated. The temperature dependence of the average torsional lifetimes of the molecules and the transition probabilities were also obtained. NQR frequency shows a nonlinear behavior with pressure, indicating both dynamic and static effects of pressure. The pressure coefficients were observed to be positive for both the lines. A thermodynamic analysis of the data was carried out to determine the constant volume temperature coefficients of the NQR frequency. The variation of spin lattice time with pressure was very small, showing that the relaxation is mainly due to the torsional motions of the molecules. PMID- 20586103 TI - Phytoglycoprotein (75 kDa) inhibits expression of interleukin-1beta stimulated by DEHP in human mast cells. AB - The purpose of this study is to investigate the inhibitory effect of a glycoprotein (CTB glycoprotein, 75 kDa) isolated from Cudrania tricuspidata Bureau (CTB) on the di-(2-ethylhexyl)phthalate (DEHP) induced expression of allergic-inflammation-related mediators in human mast cells. The changes on the levels of intracellular reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), transcription factor [nuclear factor (NF)-kappaB], and allergic inflammatory mediators [cyclooxygenase (COX)-2 and interleukin (IL)-1beta] were evaluated using Western blot and RT-PCR. Our results showed that the CTB glycoprotein in the presence of DEHP inhibits the production of intracellular ROS, the phosphorylation of ERK1/2, and p38 MAPK in HMC-1 cells. In addition, the CTB glycoprotein has suppressive effects on the transcriptional activation of NF kappaB, and on the expression levels of COX-2 and IL-1beta in DEHP-treated HMC-1 cells. In conclusion, the CTB glycoprotein has a strong anti-inflammatory effect on the activities of allergic inflammatory mediators indirectly caused by DEHP in HMC-1 cells. PMID- 20586104 TI - From discovery to application: 50 years of the vinylcyclopropane-cyclopentene rearrangement and its impact on the synthesis of natural products. PMID- 20586105 TI - An analytical method for prohexadione in Chinese cabbage and apple. AB - A residual determination method as a regulatory residue method was developed using HPLC-UVD for prohexadione residues in Chinese cabbage (Brassica pekinensis) and apple (Malus domestica). The developed method consisted of solid-liquid extraction with acidic acetonitrile and ion-suppression liquid-liquid partitioning, followed by anion exchange cartridge cleanup. The limits of detection and quantitation for the method were 0.005 and 0.02 mg/kg, respectively. The method gave good linearity in the range of 0.02-2.5 mg/kg. Accuracy and precision ranged from 84.1 to 94.1% and from 2.4 to 6.9%, respectively. Additionally, the confirmative conditions of LC-MS/MS for prohexadione were set in negative electrospray ionization mode with transitions of m/z 211.4 -> 167.5 and m/z 211.4 -> 123.5 in the selected reaction monitoring mode. The applicability of the method was demonstrated by analyzing real samples collected from local markets in Seoul, Republic of Korea. This developed method fully deserves consideration in accordance with its sensitivity, accuracy and precision required for residue analysis of prohexadione in Chinese cabbages and apples. PMID- 20586106 TI - Characterization of in vitro metabolism of capsazepine, a vanilloid transient receptor potential channel antagonist, by liquid chromatography quadrupole ion trap mass spectrometry. AB - Capsazepine is an antagonist of the transient receptor potential channel vanilloid 1 (TRPV1), which is known to play an important role in the regulation of pain and inflammation. A selective and sensitive quantitative method for the determination of capsazepine by HPLC-ESI/MS/MS was developed. The method consisted of a protein precipitation extraction followed by analysis using liquid chromatography electrospray quadrupole ion trap mass spectrometry. The chromatographic separation was achieved using a 100 * 2 mm C(18) Waters Symmetry column combined with a gradient mobile phase composed of acetonitrile and 0.1% formic acid aqueous solution at a flow rate of 220 uL/min. The mass spectrometer was operating in full-scan MS/MS mode using two-segment analysis. An analytical range of 10-5000 ng/mL was used in the calibration curve constructed in rat plasma. The inter-batch precision and accuracy observed were 10.1, 6.4 and 6.1% and 100.8, 98.5 and 106.2% at 50, 500 and 5 000 ng/mL, respectively. An in vitro metabolic stability using rat, dog or mouse liver microsomes was performed to determine the intrinsic clearance of capsazepine. The results suggest a very rapid degradation with T(1/2) ranging from 2.6 to 4.3 min and a high clearance, suggesting that drug bioavailability is considerably reduced following extravascular administrations, consequently affecting drug response. Three metabolites were identified by HPLC-MS/MS. S-hydroxylation (M + 16), oxidative desulfuration (M - 16) and desulfuration (M - 32) metabolites of capsazepine were observed following exposure to rat, dog and mouse microsomes. PMID- 20586107 TI - Usefulness of the simultaneous determination of serum levels of theophylline and its metabolites in patients medicated with theophylline preparation. AB - OBJECTIVE: Measurement of the serum level of theophylline is essential for its proper use; however, it is difficult to infer the metabolic ability of individual patients by only the serum theophylline level and to decide the appropriate medication. In this study, we simultaneously measured serum theophylline and metabolite levels in patients treated with theophylline, and investigated their usefulness. EXPERIMENTAL: The subjects were asthma patients who visited the outpatient clinic of Respiratory Medicine, St Luke's International Hospital, between April and October 2003, and were medicated with sustained-release theophylline tablets (Theodur(r)). The serum level of theophylline and its metabolites was measured by HPLC in patients who gave written consent. RESULTS: A strong correlation was noted between the serum theophylline (TP) and 1,3 dimethyluric acid (DMU) levels of 52 patients (r = 0.670), and DMU/TP was about 0.04. In a patient whose the DMU/TP was 0.216, it was recognized that metabolic ability was promoted due to a history of smoking. DISCUSSION: In this study, it was shown that simultaneous measurement by HPLC of the serum level of theophylline and its metabolites and DMU/TP was useful to assess the metabolic ability of individual patients. PMID- 20586108 TI - Clinical and sonographic parameters at 37 weeks' gestation for predicting the risk of primary Cesarean delivery in nulliparous women. AB - OBJECTIVES: To identify the clinical and sonographic parameters at 37 weeks' gestation that predict the risk of Cesarean delivery in labor for nulliparas. METHODS: This prospective observational study recruited nulliparas with singleton pregnancies at 37 weeks' gestation. Determination of the Bishop score, ultrasound measurement of the cervical length, and fetal biometry were performed. The clinical parameters studied were maternal age, height and weight and Bishop score. The sonographic parameters included fetal biparietal diameter, femur length, abdominal circumference (AC), estimated fetal weight (EFW), amniotic fluid index and cervical length. RESULTS: Four hundred and fifty-three women were examined; 57 women (12.6%) underwent an emergency Cesarean delivery in labor. Logistic regression analysis identified maternal age and height and fetal AC and EFW, but not cervical length or Bishop score, as the best predictors of Cesarean delivery. Of these predictors, maternal age and height and fetal AC at 37 weeks were included in a final model for risk scoring. The model was shown to have an adequate goodness of fit (P = 0.473), and the area under the receiver-operating characteristics curve was 0.758, indicating reasonably good discrimination. CONCLUSIONS: Maternal age and height and fetal AC and EFW at 37 weeks' gestation are the most important parameters in predicting the risk of Cesarean delivery in nulliparas; sonographic measurement of the cervical length and the Bishop score were not predictive of Cesarean delivery. A predictive model using these parameters at 37 weeks provides useful information in the decision-making process regarding the mode of delivery. PMID- 20586109 TI - Indirect enantioresolution of (R,S)-mexiletine by reversed-phase high-performance liquid chromatography via diastereomerization with [(S,S)-O,O'-di-p-toluoyl tartaric acid anhydride], (S)-naproxen and nine chiral reagents synthesized as variants of Marfey's reagent. AB - Eleven chiral derivatizing reagents (CDRs) were used for preparation of diastereomers of (R,S)-mexiletine containing a primary amino group in close proximity to the stereogenic center. One anhydride, namely [(S,S)-O,O'-di-p toluoyl tartaric acid anhydride] was synthesized and (S)-naproxen was used as such as the chiral derivatizing reagent. The other nine CDRs were synthesized by substituting one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene with six amino acid amides and three amino acids. The diastereomers were separated by reversed-phase high-performance liquid chromatography. The method was validated for linearity, accuracy, limit of detection and limit of quantification. The limit of detection was found in the range of 10-30 pmol. PMID- 20586110 TI - Molecular orbital analysis of the inverse halogen dependence of nuclear magnetic shielding in LaX3, X = F, Cl, Br, I. AB - The NMR nuclear shielding tensors for the series LaX(3), with X = F, Cl, Br and I, have been computed using two-component relativistic density functional theory based on the zeroth-order regular approximation (ZORA). A detailed analysis of the inverse halogen dependence (IHD) of the La shielding was performed via decomposition of the shielding tensor elements into contributions from localized and delocalized molecular orbitals. Both spin-orbit and paramagnetic shielding terms are important, with the paramagnetic terms being dominant. Major contributions to the IHD can be attributed to the La-X bonding orbitals, as well as to trends associated with the La core and halogen lone pair orbitals, the latter being related to X-La pi donation. An 'orbital rotation' model for the in plane pi acceptor f orbital of La helps to rationalize the significant magnitude of deshielding associated with the in-plane pi donation. The IHD goes along with a large increase in the shielding tensor anisotropy as X becomes heavier, which can be associated with trends for the covalency of the La-X bonds, with a particularly effective transfer of spin-orbit coupling induced spin density from iodine to La in LaI(3). PMID- 20586111 TI - Motor deficits and neurofibromatosis type 1 (NF1)-associated MRI impairments in a mouse model of NF1. AB - Neurofibromatosis type 1 (NF1) is a genetic disorder characterized inter alia by cognitive and motor dysfunction and appearance of high-signal foci on T2-weighted images in the brain. Nf1(+/-) mice are useful models for studying aspects of NF1, including cognitive deficits. Here we assessed their motor performance and used quantitative transverse T2 relaxation MRI to identify structural abnormalities in their brains. Nf1(+/-) mice exhibited both enhanced and reduced T2 signals in distinct brain regions compared to wild-type mice, and their motor performance was impaired. As in NF1 patients, enhanced T2 signals in Nf1(+/-) mice were observed in the thalamus and basal ganglia. Reduced T2 signals were seen in motor associated regions along the motor pathway, predominantly in the white matter of the cerebral peduncle and the optic tract. Correlation analysis between T2 signals and motor performance suggested that the motor deficits are associated with impairments in the cerebral peduncle and the amygdala. PMID- 20586112 TI - Statin medication use and the risk of biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. AB - BACKGROUND: Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate-specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP). METHODS: The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features. RESULTS: In total, 236 (18%) men were taking statins at RP. Median follow-up was 24 months for statin users and 38 for nonusers. Statin users were older (P<.001) and underwent RP more recently (P<.001). Statin users were diagnosed at lower clinical stages (P=.009) and with lower PSA levels (P=.04). However, statin users tended to have higher biopsy Gleason scores (P=.002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio "HR", 0.70; 95% confidence interval "CI", 0.50-0.97; P=.03), which was dose dependent (relative to no statin use; dose equivalentsimvastatin 20 mg: HR, 0.50; 95% CI, 0.27-0.93; P=.03). CONCLUSIONS: In this cohort of men undergoing RP, statin use was associated with a dose-dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP. PMID- 20586113 TI - Chemiluminescence of non-differentiated THP-1 promonocytes: developing an assay for screening anti-inflammatory milk proteins and peptides. AB - Human leukemic THP-1 promonocytes are widely used as a model for peripheral blood monocytes. However, superoxide production during respiratory burst (RB) of non differentiated THP-1 (nd-THP-1) cells is very low. Here we present a rapid and low-cost method for measuring the chemiluminescence (CL) of opsonized zymosan (OZ) induced RB which allows detection of Escherichia coli lipopolysaccharide (LPS) induced priming of nd-THP-1 cells on the basis of CL reaction kinetics. Maximum CL intensity obtained was 2.20 +/- 0.25 and 1.30 +/- 0.11 relative light units, while CL peak time was achieved at 18.1 +/- 2.6 and 28.7 +/- 1.3 min in primed and non-primed cells, respectively. The priming of nd-THP-1 cells with LPS evoked typical TNF-alpha and IL-6 production. We tested the effects of bovine lactoferrin and protein fractions from Lactobacillus helveticus BGRA43 fermented milk for potential anti-inflammatory effects on LPS primed nd-THP-1 cells. Four fractions were found to inhibit the OZ-induced CL in a dose-dependent manner (IC(50) 3-30 ug/mL), while lactoferrin inhibited CL to a lesser extent (IC(50) 270 ug/mL). These results suggest that measuring CL response of nd-THP-1 cells can serve as a method for screening anti-inflammatory compounds which could be used in reducing the risk of phagocyte-mediated inflammatory diseases. PMID- 20586114 TI - Comparative functional analysis of the OCH1 mannosyltransferase families in Aspergillus fumigatus and Saccharomyces cerevisiae. AB - Alpha1,6-linked mannans are an essential component of the Aspergillus fumigatus galactomannan, which is either GPI-anchored to the plasma membrane or covalently bound to the polysaccharide core of the cell wall. In Saccharomyces cerevisiae, the OCH1 gene encodes an alpha1,6-mannosyltransferase that initiates the synthesis of the alpha1,6 linked-mannan. In the A. fumigatus genome, four orthologous genes of Saccharomyces cerevisiae ScOCH1 gene were identified. Single deletion and the quadruple deletion mutants (Afoch1-4Delta) were constructed in A. fumigatus. No phenotype different from the wild-type strain was observed in all single and the quadruple mutants. The corresponding cDNAs of the AfOCH1-4 A. fumigatus orthologues were expressed in the S. cerevisiae Scoch1Delta mutant. Among the four orthologues, only AfOCH1 complemented the aggregation phenotype, the growth inhibition, the hypersensitivity to hygromycin and the protein glycosylation defects observed in the Scoch1Deltamutant. PMID- 20586115 TI - Differences in activation of MAP kinases and variability in the polyglutamine tract of Slt2 in clinical and non-clinical isolates of Saccharomyces cerevisiae. AB - The concept of Saccharomyces cerevisiae as an emerging opportunistic pathogen is relatively new and it is due to an increasing number of human infections during the past 20 years. There are still few studies addressing the mechanisms of infection of this yeast species. Moreover, little is known about how S. cerevisiae cells sense and respond to the harsh conditions imposed by the host, and whether this response is different between clinical isolates and non pathogenic strains. In this regard, mitogen-activated protein kinase (MAPK) pathways constitute one of the major mechanisms for controlling transcriptional responses and, in some cases, virulence in fungi. Here we show differences among clinical and non-clinical isolates of S. cerevisiae in the level of activation of the MAPKs Kss1, which controls pseudohyphal and invasive growth, and Slt2, which is required for maintaining the integrity of the cell wall under stress conditions and in the absence of stimulating conditions. Moreover, we report for the first time the existence of length variability in SLT2 alleles of strains with a clinical origin. This is due to the expansion in the number of glutamine encoding triplets in the microsatellite region coding for the polyglutamine (poly Q) tract of this gene, which range from 12 to more than 38 repetitions. We suggest that this variability may influence biological features of the Slt2 protein, allowing it to adapt swiftly in order to survive in unusual environments. PMID- 20586117 TI - An estimate of risk of malignancy for a benign diagnosis in thyroid fine-needle aspirates. AB - BACKGROUND: The risk of malignancy for a benign diagnosis in a thyroid fine needle aspiration is controversial because of lack of histologic follow-up. METHODS: The author reviewed the results of all thyroid aspirations with surgical resection performed during the past 13 years at Baptist Hospital of Miami and Homestead Hospital, Homestead, Florida, combined these procedures with those in the literature, and correlated risk of malignancy with percentage of biopsies performed. RESULTS: A total of 7089 aspirations and 1331 resections were performed. In the literature, the percentage of all benign cases that underwent resection ranged from 3% to 41%. Risk of malignancy decreased with an increased percentage of resections. The risk of malignancy for series with <8% of all benign aspirates resected was significantly higher than the risk for series with >or=8% of cases biopsied (15.1% vs 5.9%, P = .02). Logarithmic and linear estimates of risk of malignancy if 100% of cases were biopsied were 3% and 2.5%. CONCLUSIONS: The best estimate of the risk of malignancy for a benign diagnosis in a thyroid fine-needle aspiration is 2.5%-3%. This level of risk is affected by the percentage of benign cases that are resected. PMID- 20586118 TI - Should "atypical follicular cells" in thyroid fine-needle aspirates be subclassified? AB - BACKGROUND: Recently reported Bethesda terminology suggests the use of the term "atypical follicular cells" for thyroid fine-needle aspirates. Previous work has suggested that some types of "atypical follicular cells" have different risks of malignancy. METHODS: The author reviewed the results of all thyroid aspirations with surgical resection performed during the past 13 years at our institution, subclassified the "atypical follicular cells," and compared their relative risk of malignancy. RESULTS: During the 13 years in question, a total of 7089 cases were aspirated with 1331 resections. A total of 548 (14%) of all cases were classified as "atypical follicular cells," and 204 (37%) were resected with an overall risk of malignancy of 25%. The risk of malignancy for atypical follicular cells subclassified as "rule out papillary carcinoma" was significantly higher (38%) than the other atypical cells. The risk of "rule out Hurthle cell neoplasm" was, at 7%, significantly lower than the other cases of atypical follicular cells (P<.001 and P<.02, respectively). CONCLUSIONS: Different types of "atypical follicular cells" have significantly different risks of malignancy. This disparity of risk should be communicated by the cytologist. PMID- 20586119 TI - Modeling of congenital erythropoietic porphyria by RNA interference: a new tool for preclinical gene therapy evaluation. AB - BACKGROUND: Congenital erythropoietic porphyria (CEP) is a severe autosomal recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We recently demonstrated the definitive cure of a murine model of CEP by lentiviral vector mediated hematopoietic stem cell (HSC) gene therapy. In the perspective of a gene therapy clinical trial, human cellular models are required to evaluate the therapeutic potential of lentiviral vectors in UROS-deficient cells. However, the rare incidence of the disease makes difficult the availability of HSCs derived from patients. METHODS: RNA interference (RNAi) has been used to develop a new human model of the disease from normal cord blood HSCs. Lentivectors were developed for this purpose. RESULTS: We were able to down-regulate the level of human UROS in human cell lines and primary hematopoietic cells. A 97% reduction of UROS activity led to spontaneous uroporphyrin accumulation in human erythroid bone marrow cells of transplanted immune-deficient mice, recapitulating the phenotype of cells derived from patients. A strong RNAi-induced UROS inhibition allowed us to test the efficiency of different lentiviral vectors with the aim of selecting a safer vector. Restoration of UROS activity in these small hairpin RNA transduced CD34(+) cord blood cells by therapeutic lentivectors led to a partial correction of the phenotype in vivo. CONCLUSIONS: The RNAi strategy is an interesting new tool for preclinical gene therapy evaluation. PMID- 20586120 TI - T cell memory: DCs gather crumbs to feed memory. PMID- 20586121 TI - T cell responses: Vesicle fusion keeps cells moving. PMID- 20586122 TI - Autoimmunity: New players in lupus nephritis. PMID- 20586123 TI - Antiviral immunity: Speed and endurance required. PMID- 20586124 TI - Tumour immunology: Run and hide. PMID- 20586125 TI - HDL: the good, but complex, cholesterol. More HDL is better, but the benefits may depend on how you get there. PMID- 20586126 TI - Bringing clarity to CRP testing. Wider use is in the offing for this simple blood test to gauge cardiac risk. PMID- 20586128 TI - Cardiac cancer--uncommon but possible. PMID- 20586127 TI - Protecting the heart from cancer therapy. Battling cancer can have long-term effects on the heart. PMID- 20586129 TI - New prescription for some leftover drugs. PMID- 20586130 TI - [Surgical ligation of patent ductus arteriosus in premature infants]. PMID- 20586131 TI - No sailing away from heart disease. PMID- 20586132 TI - Ask the doctor. I tried taking niacin to increase my HDL but didn't like the flushing it caused. A friend told me about no-flush niacin, which works like a charm. Why not tell your readers about it? PMID- 20586133 TI - Reconstruction of the auricle. Preface. PMID- 20586134 TI - Hepatotoxicity associated with chinese skullcap contained in Move Free Advanced dietary supplement: two case reports and review of the literature. AB - Move Free Advanced is a widely available dietary supplement in the United States, marketed to comfort sore joints and improve flexibility and mobility. This product contains glucosamine, chondroitin, hyaluronic acid, and Uniflex proprietary extract, which is a combination of Chinese skullcap and black catechu. We describe two patients who developed hepatotoxicity after ingesting a Move Free Advanced product. In both patients, the hepatotoxicity resolved after discontinuation of the supplement. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6 for both patients) between the patients' development of hepatotoxicity and the Move Free Advanced supplement. Based on a review of the literature, the herbal extract Chinese skullcap is the most likely cause of the hepatotoxicity. To our knowledge, these two cases are the first to be published regarding possible hepatotoxicity associated with Move Free Advanced. Patients seeking dietary supplements for osteoarthritis may want to avoid glucosaminechondroitin products such as Move Free Advanced that also contain Chinese skullcap. PMID- 20586136 TI - Animals in surgery--surgery in animals: nature and culture in animal-human relationship and modern surgery. AB - AThis paper looks at the entangled histories of animal-human relationship and modem surgery. It starts with the various different roles animals have in surgery -patients, experimental models and organ providers--and analyses where these seemingly contradictory positions of animals come from historically. The analyses is based on the assumption that both the heterogeneous relationships of humans to animals and modern surgery are the results of fundamentally local, contingent and situated developments and not reducible to large-scale social explanations, such as modernization. This change of perspective opens up a new ways of understanding both phenomena as deeply interwoven with the redrawing of the nature-culture divide. PMID- 20586137 TI - The animal as surgical patient: a historical perspective in the 20th century. AB - Current veterinary history has not engaged significantly with patient histories. In many historical accounts of veterinary medicine, animal patients are backgrounded or completely invisible. Yet modern veterinary medicine, in its dominant form of companion animal practice, has become increasingly patient centred. The modern animal patient is accorded something near full subject status in many veterinary clinical interactions. Embracing this raises issues of how to handle animals in veterinary history. Animals are the recipients of veterinary medicine, they exert agency in the clinic and field, yet they have remained problematical for the historian and sociologist, who have remained anthropocentric in orientation. This paper explores different constructions of the veterinary surgical patient in the 20th century in an attempt to begin examination of veterinary history as an animal-patient history "from below." In doing so, a trajectory of the development of British 20th-century veterinary medicine is presented which suggests the value of minding animals in historical accounts. Further interdisciplinary studies of veterinary procedures and practices are needed in order to foreground animals more and evaluate their subject status within historical and contemporary veterinary medicine. PMID- 20586138 TI - Picturing the pain of animal others: rationalising form, function and suffering in veterinary orthopaedics. AB - Advances in veterinary orthopaedics are assessed on their ability to improve the function and wellbeing of animal patients. And yet historically veterinarians have struggled to bridge the divide between an animal's physicality and its interior experience of its function in clinical settings. For much of the twentieth century, most practitioners were agnostic to the possibility of animal mentation and its implications for suffering. This attitude has changed as veterinarians adapted to technological innovations and the emergence of a clientele who claimed to understand and relate to the subjective experiences of their animals. While visualising technologies and human analogies have shaped the nuts and bolts of veterinary orthopaedic practices, an emerging awareness of the inability of radiographic images to apprehend or correlate to a patient's experience of their function reliably has required veterinarians to place a greater emphasis on the owner's knowledge of the "selves" inhabiting their animals. Rather than simply basing clinical judgments on the "look" of their patients, the indeterminacy in the connection between form and function has compelled veterinarians to put questions regarding particular human-animal relationships near the centre of their practices, not least in orthopaedic surgery. PMID- 20586139 TI - The animal issue in xenotransplantation: controversies in France and the United States. AB - In recent years scientists have created genetically modified pigs for the purpose of xenotransplantations. These are transplants of animal organs into human patients. But xenotransplantation has a long history. Since the early twentieth century, many surgeons tried to insert animal organs into human and non-human bodies. This paper examines the controversies that these innovations have caused in the United States and France, including the notion of the objectification of animals. Three phases are described. The historical review shows that far from the choice of pigs being "natural" it turns out to be recent and to follow controversies surrounding the possible use of primates. During the last phase, the scientists have internalized the "animal issue" in their practice: the official donor is now the pig, and the animals are treated respectfully during all the lab manipulations. Since pigs are different from humans they can be objectified and thus absorbed. This objective distance is, however, threatened by new discourses on animal rights, by genetic manipulations that "humanise" pigs, and by scientific practice itself that recognizes a moral proximity between pigs and men. PMID- 20586141 TI - Death of the specialist, rise of the machinist. PMID- 20586140 TI - The emergence of "implant-pets" and "bone-sheep": animals as new biomedical objects in orthopaedic surgery. AB - In this paper we examine the role of animals in orthopaedic surgery and research in the 1960s. We describe their different roles as patients and laboratory models in the emergence of two new biomedical objects that we call "implant-pets" and "bone-sheep." For this purpose, the ways of practicing (veterinary) orthopaedic surgery and of "materializing," or bringing into being, complex and heterogeneous biomedical objects are analyzed as the coevolving histories of humans and animals. Focusing on non-discursive material practices, we use the concept of "articulation" in order to explore the inventive and intervening character of biomedical practices that led to the existence of implant-pets and bone-sheep. Our analysis interprets the distribution of human-like and animal-like character features and values to these animals not as the result of a stable animal-human boundary, but as the effect of diverse interactions in contingent historical situations. This dynamic-relational approach makes it possible to investigate the drawing of human-animal boundaries in the making and thus contributes in a new way to the study of animal-human relationships in history. PMID- 20586142 TI - Doppler flowmetry in preeclampsia. PMID- 20586143 TI - Effect of ankaferd blood stopper on hemostasis and histopathological score in experimental liver injury. AB - AIM: To investigate intra-abdominal, local histopathological and hemostatic effects of Ankaferd (ABS) in an experimental liver injury. METHODS: Forty rats were randomly assigned to the primary suture group (PS) (n = 15), ABS group (n = 15) and control group (n = 10). A wedge resection was performed on the left lobe of the liver. In the primary suture group, the liver was sutured with polypropylene material, while in ABS group the liver surface was covered with ABS. Adhesion, histo-pathological scores and hydroxyproline levels were measured postoperatively on day 3 and day 15. RESULTS: The mean bleeding time was 7.5 sec shorter in the ABS group (6.5 sec-13.5 sec) and 107 sec shorter in PS group. AST, ALT, total bilirubin and ALP values complete blood count (CBC) did not change. Intra-abdominal adhesions were the same in PS and ABS groups on 3rd (2.20 +/- 1.30 vs 2.0 +/- 1.11) and 15th (1.60 +/- 0.54 vs 1.25 +/- 0.7) days postoperatively. Histopathological scores were better in the ABS group than in the primary suture group on 3rd (2.5 +/- 0.5 vs 5.25 +/- 0.2, p = 0.006) and 15th (1.65 +/- 1.7 vs 3.15 +/- 1.0, p = 0.025) days postoperatively. Hydroxyproline levels were higher in ABS group on postoperative 15th day (17.12 microg/tissue vs 13.69 microg/tissue; p = 0.005). CONCLUSION: These data suggest that ABS in experimental liver trauma causes favorable histopathological scores and shorter hemostasis time and higher hydroxyproline levels (Tab. 2, Fig. 2, Ref. 35). PMID- 20586144 TI - The effect of antioxidants (N-acetylcysteine and melatonin) on hypoxia due to carbonmonoxide poisoning. AB - We aimed to determine the effect NAC (N-acetylcysteine) and melatonin on the histopathological and biochemical paramethers in the rats poisoned with CO (Carbon monoxide) experimentally. Winster albino female rats were placed in a plexiglass chamber and they were poisoned with CO. After the poisoning, rats were randomly divided into 3 groups. The group given only normal saline, was used as a control group (n = 9). The second group was given 30 mg/kg intraperitonally NAC (n = 10). And the third group was treated with 10 mg/kg of melatonin intramuscularly (n = 9). It is determined that some biochemical values affected by NAC but not by melatonin. CK, ALT, Lactate, MDA levels were significantly higher in NAC group than control and Melatonin group (p < 0.01 for all comparisons). Thiol level was lower in NAC group than control group and Melatonin group (p < 0.01 and p < 0.001, respectively). There were no statistical significant differences between the melatonin and control group. There were statistically significant difference between control, NAC and Melatonin groups according to brain and lung tissue damage. It is shown that both NAC and Melatonin are reducing the brain and lung tissue damage of CO poisoning but due to biochemical results worsened by NAC, Melatonin may recommend for CO poisoning (Tab. 3, Ref. 21). PMID- 20586145 TI - Bacterial translocation in experimental stroke: what happens to the gut barrier? AB - The reasons of post-stroke infections are still incompletely understood. Bacterial translocation (BT), the passage of viable microbes across an even anatomically intact intestinal barrier, has been described in many critical illnesses. To date, it has not been studied as a source of infection in an animal stroke model. To address this, a permanent left middle cerebral artery occlusion (MCAO) model in rats was used. After 24, 48, and 72 hours (h), sham and experimental groups were sacrificed and samples were taken for BT. Similarity between bacteria detected in tissues (blood, mesenteric lymph node, liver, spleen, and lung) and intestinal microflora was shown with phenotypic methods and antibiotyping. Possible ileum tissue injuries were shown by histopathologic examination (including morphometric analysis). Although there was no bacterial proliferation in the sham groups, 55.5%, 45.4%, and 30% bacterial proliferation was detected in MCAO groups at postoperative hour 24, 48, and 72, respectively. In MCAO groups the bacterial proliferation in tissues and ileum tissue injury scores were higher over time compared to sham groups (p < 0.05). Our findings support the view that stroke, itself leads to mucosal damage and bacterial translocation (Tab. 5, Fig. 2, Ref. 27). PMID- 20586146 TI - Evaluation of the relationship between insulin resistance and plasma tumor necrosis factor-alpha, interleukin-6 and C-reactive protein levels in obese women. AB - OBJECTIVE: To investigate the relationship between insulin resistance and tumor necrosis (TNF)-alpha, interleukin (IL)-6, C-reactive protein (CRP) in obese women. BACKGROUND: Obesity and type 2 diabetes are associated with insulin resistance, the mechanisms of which remain poorly understood. MATERIALS AND METHODS: Forty obese (35.8 +/- 9.6 years) and 20 non-obese women (31.1 +/- 7.7) were recruited between June 2002 and February 2003 at the Okmeydany Training and Research Hospital, Istanbul, Turkey. The obese group was equally divided into two according ?to their WHR (> 0.8 and 0.8). Subjects with blood pressure values higher than 140/90 mmHg, pathological findings on standard 12-lead EC3 and leukocytosis and glucose levels > 100 mg/dl were excluded. RESULTS: Plasma insulin (p < 0.0001) and fasting glucose levels (p<0.0001), and HOMA values (p < 0.0001) in the obese group were higher than in the controls. Serum triglyceride and VLDL levels were higher in the obese group (p < 0.0001 in both), whereas HDL cholesterol levels were higher in the lean control group (p < 0.0001). However, no difference was observed between two groups in terms of total cholesterol and LDL-cholesterol levels. The serum levels of both TNF-alpha, IL-6 and CRP were found elevated in the obese group (p < 0.05, p < 0.05, p < 0.01, respectively). In the subgroup analysis, only the HOMA values and TNF-alpha levels were found higher in the android obese group (p < 0.05 and p < 0.0001, respectively). CONCLUSION: Insulin resistance seems to be one of the major causes of obesity related complications due to increased secretion of TNF-alpha, IL-6 and CRP together with android obesity (Tab. 5, Ref. 33). PMID- 20586147 TI - Complementary therapy in diabetic patients with chronic complications: a pilot study. AB - BACKGROUND: Oxidative stress and dysregulation of antioxidant function play a pivotal role in the diabetic complications. METHODS: Fifty-nine patients with diabetes were randomly assigned into three groups. 1) PL group (n = 19): Polarized light (PL) was applied to neuropathic ulcers of diabetic foot twice daily for ten minutes in pulse regimen during three months. 2) QALA group (n = 20): Antioxidants (60 mg hydrosoluble CoQ10, 100 mg alpha-lipoic acid (ALA) and 200 mg vitamin E) were used in two daily doses for three months. 3) QALAPL group (n = 20): Patients used antioxidants along with PL applications. To test for differences in means, paired Student's t-test (before and after three months) was used. RESULTS: Three months application of PL significantly increased plasma concentrations of coenzyme Q10, alpha-tocopherol, tau-tocopherol and beta carotene, and decreased lactate dehydrogenase (LDH) activity. Supplementation with antioxidants decreased plasma lipid peroxides, increased concentration of CoQ10 and improved echocardiographic parameters. Simultaneous application of PL and antioxidants significantly stimulated plasma CoQ10 and alpha-tocopherol concentrations, decreased LDH activity and contributed to improvement in heart left ventricular function in diabetics. CONCLUSION: Thus the data show that supportive therapy with PL along with the antioxidants hydrosoluble CoQ10, alpha lipoic acid and vitamin E is an effective way of controlling the complications of type 2 diabetes (Tab. 7, Fig. 2, Ref. 44). PMID- 20586148 TI - Serum levels of leptin, adiponectin, retinol binding protein 4 and leptin/adiponectin molar ratio as another possible marker of insulin resistance in obese. AB - AIM: To determine the relationship between some adipokines and insulin resistance (IR) in obese. MATERIALS AND METHODS: 47 individuals were divided--1. according to BMI to subgroups with normal weight, overweight and obesity, 2. according to IR HOMA index to subjects with IR (IR HOMA > 1.88) and subjects without IR. Except the basic biochemical parameters, serum level of fasting insulin, leptin, retinol binding protein 4 (RBP4) (RIA), adiponectin (ELISA) and leptin/adiponectin (L/A) molar ratio were examined. RESULTS: 1. In correlation to BMI--subjects with BMI > 30 showed significantly higher level of insulin (16.1 +/ 4.1/5.9 +/- 4.1), leptin (51.9 +/- 26.4/14.7 +/- 14) and molar ratio LA (3.1 +/- 1.8/0.48 +/- 0.2) (p < 0.01) and significantly lower level of adiponectin (18.9 +/- 6.3/35.5 +/- 10.5) (p < 0.01) in comparison to both other subgroups (normal weight, overweight). There was no statistically significant difference in RBP4 level between all subgroups, although the highest level of RBP4 was observed in subjects with BMI > 30. In correlation to IR-- subjects with IR showed significantly higher BMI (35.7 +/- 5.8/24.8 +/- 2.6), insulin (15.5 +/- 7.1/4.8 +/- 1.6), leptin (47.2 +/- 29.2/15.1 +/- 13), L/A molar ratio (2.7 +/- 0.3/0.5 +/ 0.1) (p < 0.01), and RBP4 (561.6 +/- 152.5/450.9 +/- 101.7 (p < 0.05) as well. In IR subjects, serum level of adiponectin was significantly lower in comparison to subjects without IR (19.8 +/- 6.3/32.2 +/- 0.8) (p < 0.01). CONCLUSION: Decreased level of adiponectin and increased level of leptin, RBP4 and leptin/adiponectin molar ratio in obese can be also considered as a marker of developing insulin resistance (Tab. 2, Ref. 23). PMID- 20586149 TI - Gastric lavage with normal saline: effects on serum electrolytes. AB - OBJECTIVE: The aim of this study is to determine the intensity of changes in serum calcium, ionized calcium, and magnesium levels after gastric lavage with normal saline in patients with amitriptyline intoxication. MATERIAL AND METHODS: In this study, thirty patients older than 16 years with the history of intoxication with amitriptyline were included. After the baseline serum calcium, ionized calcium, and magnesium levels had been measured, gastric lavage with normal saline was performed. Serum levels of calcium, ionized calcium, and magnesium were monitored at 15 minutes, 6 hours, and 12 hours. RESULTS: Serum calcium levels decreased significantly from 9.32 +/- 0.47 mg/dL to 8.40 +/- 0.61 mg/dL (15 minutes, p < 0.001), 8.92 +/- 0.54 mg/dL (6 hours, p < 0.001), and 8.93 +/- 0.54 mg/dL (12 hours, p < 0.001). Serum ionized calcium levels decreased significantly from 1.26 +/- 0.10 mmol/L to 1.20 +/- 0.07 mmol/L (15 minutes, p = 0.004), 1.21 +/- 0.08 mmol/L (6 hours, p = 0.024), and 1.21 +/- 0.08 mmol/L (12 hours, p = 0.034). Serum magnesium levels decreased from 2.41 +/- 0.43 mg/dL to 2.04 +/- 0.25 mg/dL (15 minutes, p < 0.001), 2.14 +/- 0.26 mg/dL (6 hours, p < 0.001), and 2.16 +/- 0.25 mg/dL (12 hours, p < 0.001). CONCLUSION: Our study demonstrated that gastric lavage with normal saline can cause a statistically significant decrease in serum calcium, ionized calcium, and magnesium (Fig. 4, Ref. 8). PMID- 20586150 TI - Our experience with chemosterilized antigen-extracted autolyzed allografts (AAA) in a series of elective foot and ankle procedures. AB - BACKGROUND: It is generally accepted that the golden standard for bone grafting is the autogenous bone. OBJECTIVES: The purpose of our retrospective study was to review and show a single-surgeon experience with chemosterilized antigen extracted autolyzed (AAA) bone allograft in foot and ankle procedures. METHODS: The study population consisted of 35 patients who were operated on between January 2005 and Januray 2009. All patients were eligible for inclusion in this study if their surgery was performed using the chemosterilized antigen-extracted autolyzed allogeneic bone (AAA). In this study, the authors wanted to emphasize the effectiveness of AAA bone grafts in reconstructive foot surgery. All allografts were harvested, prepared and obtained from West Hungarian Regional Tissue Bank Gybr. RESULTS: Union was defined both clinically and radiografically and was established on subjective and objective criteria. A total of 35 consecutive foot and ankle implant procedures were performed, there were 32 healed sites (91.43%) 2 nonunion (5.71%) and 1 deep infection complication (2.86%). CONCLUSION: The authors have shown that AAA allograft is appropriate for reconstructive procedures of the foot and ankle with a low rate of complication (Tab. 1, Fig. 2, Ref. 8). PMID- 20586151 TI - Significant associations of acute gastrointestinal haemorrhage and the estimation of effectiveness of the newly proposed acute abdominal bleeding score (AABS) in emergency patients. AB - This study was carried out in different units of surgical wards of Khulna Medical College Hospital, Bangladesh. Among the total number of 284 patients about 88.7% (252) was admitted for the upper GIT pathology and in relation to this, lower GIT bleeding was less common 11.2% (32). In the question of emergency surgical management, 156 (61.9%) patients out of 252 upper GIT bleeding patients needed an emergency surgery, whereas it was only 12 (37.5%) out of the rest of lower GIT bleeding patients. Fortunately, in this study, it was clearly found that, in case of bleeding control, 234 (82.3%) patients had it without intervention. This study also suggests that only 29.6% (84) patients had specific clinical manifestation out of 284 patients, followed by 43% (122) who had vague signs-symptoms and the rest 27.5% (78) had latent symptoms of acute haemorrhage. In case of diagnosis of acute hemorrhagic patients, only 34.5% (98) was diagnosed clinically. A 36% (102) patient out of 284 patients was diagnosed by ultrasound of abdomen and 14.8% (42) was diagnosed by endoscopy. It was a very remarkable finding of this study that 33.8% (96) patients were remained undiagnosed till admission to first 24 hours and among 284 hemorrhagic patients, only 7.7% (22) required the emergency surgery on admission. In the type of acute episodic bleeding as well as in associated family history, some significant positive associations were found. The most important contribution of this clinical study was a very new but effective score (Acute Abdominal Bleeding Score=AABS) for the diagnosis. Also the clinical status of patients had been proposed which could be a very good tool for measuring the severity of acute abdominal hemorrhage in patients on admission (Fig. 6, Tab. 7, Ref. 46). PMID- 20586152 TI - Complicated course after sleeve gastrectomy for obesity. AB - The authors present a case of a 52-year old female patient with sleeve gastrectomy for obesity. Two major complications occured after the surgery. The first one was a leakage on the third day after the surgery. The routine swallow examination on the first day after the surgery was normal. The pathological secretion from the drainage occurred on the third day after the surgery with a simultaneous increase in inflammatory markers. There were no clinical signs of sepsis. An indication for laparoscopic revision was done and a small defect in the staple line was identified. The oversewing of the small defect on the stomach was performed. Immediately after the second surgery the patient was clinicaly without any problems. The inflammatory markers decreased promptly after the surgery. The second complication was presented with decompensated psychosis, which developed on the 4th day after the second surgery. The patient complained of problems with swallowing despite the fact that the swallow contrast examination was normal. The patient received her psychiatric medication intravenously. The problem with swallowing was not based on any organic reason, and lasted for 4 weeks. During this period the patient was fed only parenterally. Almost 6 weeks after the surgery the patient became compensated and was dismissed. We would like to point out to the problems potentially occuring in patients with a psychiatric disease. Good compensation and stabilization of psychiatric disease is a condition that has to be met before a surgery (Tab. 1, Fig. 1, Ref. 21). PMID- 20586153 TI - What if skin eruption is not caused by allergic reaction to drugs? AB - In this case report authors have described a case of a 39 years old Caucasian single man who was unsuccessfully treated for an allergic reaction to drugs by multiple dermatologists, due to two etiologically different diseases. It was a classical second stage syphilitic infection and positive serologic tests for HIV infection, proved by screening and confirmatory tests. Syphilitic infection was treated and followed up by dermatologist and for the treatment of HIV infection, the patient was referred to the Centre for treatment HIV/AIDS in Kosice (Fig. 4, Ref. 3). PMID- 20586154 TI - Management of pituitary macroprolactinoma in a 27-year-old male patient from Taiwan. AB - OBJECTIVES: The aim is to document the success of bromocriptine pharmacotherapy in a patient with gigantoprolactinoma. RESULT: The management of the patient was not appropriate at the beginning, because he underwent an operative therapy after the ophthalmological examination and MR without previous internal- endocrinological examination and pharmacotherapy. The endocrinologist participated in the patient management later, after the unsuccessful operative and when the patient's status was characterized by hyperprolactinaemia 15,000 ug/l and by hypopituitarism. Bromocriptine therapy immediately at the beginning would enable the patient to avoid several surgical interventions and subsequent complications with a high probability. CONCLUSION: The case report presents the failures at the beginning of diagnostic and therapeutic management of the patient with hyperprolactinaemia due to macroprolactinoma. It is both the example and the proof of irretrievability of general internal medicine, endocrinology and other internal disciplines in clinical practice. It confirms the integrating and coordinating function of the internal medicine specialist in clinical medicine (Tab. 1, Ref. 13). PMID- 20586155 TI - [Spinal cord stab injury associated with modified Brown-Sequard syndrome symptoms -a case review and literature overview]. AB - Authors present case-report of young man with incomplete spinal cord injury after penetrating stab wound. Knife blade entered the skin in the level C3/4 in the back of the neck and directed to the right and downward. Both dorsal spinal cord columns and right half of spinal cord were transected. Neurological presentation was Brown-Sequard syndrome combined with dorsal columns syndrome. Wound revision was performed followed by dural closure. 18 month after injury significant neurological improvement of right hemiparesis was recorded and the patient is self-sufficient. Spinal cord stab wounds are rare. Typical clinical symptomatology is incomplete spinal cord injury. Clinical improvement of Brown Sequard syndrome in our patient entirely corelates with literature. PMID- 20586156 TI - [Reliability of load-sharing classification in indications for anterior vertebral body replacement in thoracolumbar spine fractures]. AB - INTRODUCTION: So far, the Load-Sharing Classification (LSC) has been the commonest method employed to identify indication for anterior replacement of vertebral bodies in thoracolumbar spine fractures. The aim of this study was to verify reliability of the LSC method in indications for anterior replacement surgery. METHODS: Fractures were examined using x-ray, CT and MRI methods. The prospective study included only patients with type A3 comminuted fractures (AO classification) of the thoracolumbar vertebrae (Th11-L2), with MRI confirmed grade 3 or 4 intervertebral disc injuries (according to Oner) and with no concomitant nerve injuries. All fractures were treated using isolated posterior transpedicular (TP) fixation. 18 months after the procedure, angulation of the regional kyphosis, screw rupturing, Visual Analogue Scale (VAS) scores at rest and under loading, Pain Scale (PS) scores and Work Scale (WS) scores were assessed. The study group included 42 patients aged 27-72 years (the mean age was 51.55 y.o.a.), 28 subjects were males and 14 females. Using the LSC classification system, the study group was divided into two subgroups, one including patients with LSC up to grade 6 - Group A (18 subjects) and the other one including patients with LSC 7 to 9 - Group B (24 subjects). RESULTS: Statistical assessment of clinical (PS, WS, VAS at rest and VAS after loading) and radiological findings (the degree of kyphotic changes) at month 18 identified no statistically significant correlations between the two subgroups. TP fixation failures (srews rupturing) occured only in Group A in two subjects. DISCUSSION: Based on the LSC, Group B was expected to have inferior outcomes, however, this was not the case in our study group. Therefore, it can be concluded that LSC is not a reliable predictor of the final clinical and radiological findings in the type A3 fractures with grade 3 or 4 TH-L intervertebral disc injuries. The defined LSC 6- point threshold for indications for anterior vertebral body and disc replacements is arguable. CONCLUSION: The authors do not consider the LSC method sufficiently reliable for determining indications for anterior replacements. PMID- 20586158 TI - [Peroperative detection of pulmonary lesions during mini-invasive surgery]. AB - Currently, peroperative palpatory examination of the lungs represents standard method, however the development of the new mini-invasive surgery techniques devoid of palpable facilities, demands utilization of different procedures. The authors present their experiences involving detection of pulmonary lesions during thoracoscopic surgery visually, by endoscopic instruments, preoperative dye marking and peroperative ultrasonography via an endoscopic ultrasonic probe (all performed in Liberec District Hospital a.s.). The article describes operation techniques and tactics of thoracoscopic surgeries performed with pulmonary pathological processes in both subpleural and pulmonary parenchyma locations. PMID- 20586159 TI - [Iatrogenic injuries of the pulmonary artery]. AB - The injury of major thoracic vessels always presents life threatening condition. In our case report we present iatrogenous pulmonary artery lesion caused by Swan ganz catheter during invasive intraluminal pulmonary pressure measurement as a part of examination for cardiosurgical mitral valve replacement. There are no files describing successfully treated patients with vast pulmonary artery trunk injury rather than particular case reports. Although severe iatrogenous injury is being discussed, the outcome for the patient is thank to early surgical treatment (the application of recombinant coagulation factor VII - Novoseven, blood recuperation, therapeutic hypothermia) and professional postoperative care maximally beneficial. In the discussion and conclusion authors summarize therapeutical procedures that led to saving a patient's life. PMID- 20586160 TI - [Malignant ascites--optional management using hyperthermic peroperative chemotherapy (HIPEC)]. AB - 146 procedures using hyperthermic intraoperative peritoneal chemotherapy (HIPEC) were performed in 121 patients in the FNB Surgical Clinic, during 2000-2008. During these procedures, ascites was detected in 30 subjects (24.8%) and its volume was 250-11,000 ml. The patients concerned could not undergo radical surgery for their GIT or gynecological tumors. The patient group was divided into two subgroups. Subgroup A (22 subjects) included subjects, in whom at least palliative debulking of the tumors (usually total omentectomy) was feasible, and the procedure was followed by HIPEC. Subgroup B (8 patients) included subjects who could not undergo even the minimum debulking procedure because of extensive tumorous spread in their abdominal cavity, underwent only HIPEC. Out of the total of 22 subjects in Subgroup A, ascites was not postoperatively recorded in 17 patients. In 5 patients, ascites was gradually formed from month 6.3 onwards, however, it only reached subclinical levels. In this subgroup, 7 patients exited (at the mean postoperative month 11.7), the remaining 15 patients were surviving at that time, out of whom 9 patients were surviving for more than 1 year after the procedure, 4 subjects were surviving for over 2 years after the procedure and 2 patients for over 4 years. The geometric mean survival time 16.49 months, standard deviation of 1.57. In Subgroup B (8 patients), no ascites was detected in 3 subjects until their death (37.5%), further 5 subjects presented with ascites at the mean postoperative month 7.25. These patients survived for 2-23 months. The geometric mean survival time was 6.83 months, standard deviation of 2.12. There was a statistically significant difference between the two subgoups in the survival time parametres (p = 0.009), thereas, the difference in ascites relapse rates was statistically insignificant (p = 0.12). In the whole study group, in-hospital morbidity was 16.6% and lethality 3.3%. CONCLUSIONS: HIPEC with/without debulking is an efficient method for controlling, managing or preventing the development of malignant ascites, it extends the mean survival time of the patients (especially when bulking is feasible) with low morbidity and lethality rates of the procedure. PMID- 20586161 TI - [Mesenteric ischemia--late diagnosis or managed disease?]. AB - AIM: Diagnosis and therapy of mesenteric ischaemia as the cause of an acute abdomen is a serious problem because of its 60-80% mortality. The study presents experience with diagnosis and therapy of this disease and it compares its results with those in the literature. MATERIAL AND RESULTS: Throughout the years 2000 2009, there were 39 patients surgically treated with mesenteric ischaemia (17 men, 21 women, the average age 73 I 9.43). 38.46% of patients underwent resection of small and large bowel, in 33.3% only a part of small intestinum was resected, and in two cases (5.13%), the resection was combined with the embolectomy of artery mesenteric superior. In 23.1% of patients, only an explorative laparatomy was performed, because of an extended affection. Four patients were reoperated (dehiscence of anastomosis, perforation of small bowel, dehiscence of the wound, enterocutaneous fistula). 23% of patients needed ventilation because of postoperative complications such as respiratory insufficiency, sepsis and heart failure. There was 53.8% mortality. The abdominal pain (79%), vomitus (61.5%) and subileus (35.9%) predominated in the clinical picture. Leucocyts were elevated in 58.97% of patients. X ray examination showed non specific findings, and ultrasonography has proven to be successful in 42.3% of cases. CONCLUSION: Mortality of patients is significantly increased by low success rate of the depictive methods, non-specific clinical picture, co-morbidity in elderly patients and by late arrival to hospital. PMID- 20586162 TI - [Perforation of the intestine--rare complication of choledocholithiasis]. AB - Endoscopic biliary stent insertion is a well-established treatment for hepatic, biliary or pancreatic disorders. A routine change of endoprostheses after 3 mo is a common practice but this can be prolonged to 6 mo. An bowell perforation resulting from a migrated biliary stent is a rare complication of endoscopic stent placement for benign or malignant biliary tract disease. We describe the case of a 84-year-old woman with a history of abdominal surgery in which a migrated biliary stent resulted in an ileal perforation. Patients with comorbid abdominal pathologies, including abdominal hernia, parastomal hernia, or colonic diverticuli, may be at increased risk of perforation from migrated stents. PMID- 20586163 TI - [Rare tumors of the gallbladder and bile ducts. A case review]. AB - The authors deal with the problem of benigh tumours of the bile duct which might occur as a very suprising intraoperative finding instead of preoperatively diagnosed "gallstones". This situation can happen because of possible mistakes that might accompany today's modern practical investigative techniques. The presented report is an example of the pre-operatirely assumed choledocholithiasis which was not confirmed during the operation. Instead a rare bile duct tumour was found. PMID- 20586164 TI - [Surgical treatment of liver and pulmonary metastases of colorectal carcinoma]. AB - THE AIM: The aim of the work was to evaluate the set of 10 patients, who were operated on hepatic and pulmonary metastases of colorectal carcinoma at the Surgical Clinic of Medical Faculty of Charles University and Faculty Hospital in Plzen in years from 2005 till 2009. With regard to limited experience with the patients who underwent hepatic as well as pulmonary resection, we focused on the evaluation of a long-term survival of the patients and their mortality and morbidity. THE SET OF THE PATIENTS: In years from 2005 till 12/2009 we operated 10 patients during whose affection there occurred hepatic and pulmonary metastases of colorectal carcinoma and these were solved surgically. This concerned 5 men and 5 women at an average age of 62.4 years (42-71 years). In 10% it was hepatic resection in the first period after the operation of primary carcinoma, it was the first performance on the hepatic parenchyma in 90%. THE RESULTS: Morbidity of the set was 20.1% regarding hepatic resections and 5.6% regarding pulmonary resections. A 30-day postoperative mortality was 0%. In three cases a hepatic involvement was bilateral, in two cases in the left lung and 5 patients had an involvement of the right pulmonary lobe. In 4 cases primary carcinoma was in the rectum and in 6 cases in the large intestine. The period of three months was an average time between hepatic and pulmonary resection. Resection on liver parenchyma was the most often performance and metastasectomy with the help of laser on the pulmonary parenchyma. Rectal carcinoma spread into lungs in 50%. An average time of a 5-year survival in the patients after resection of hepatic and pulmonary metastases of colorectal carcinoma was 26%. THE CONCLUSION: Hepatic and pulmonary resection in the selected patients with generalized colorectal carcinoma extends the period of a survival and does not worsen the quality of the life. The patients after resection of both--hepatic and pulmonary metastases have got a worse long-term survival than the patients being only after hepatic resections. PMID- 20586165 TI - [Stapler procedure for anal prolapse and hemorrhoids: long-term results]. AB - INTRODUCTION: The surgical treatment of internal hemorrhoids and anal canal prolapse using stapler technique was introduced to clinical practice by Longo, as soon as in 1993. Few years later, Czech surgeons became familiar with this technique, and even it is being performed in many surgical departments of our country at the present time. At the Dept. of Surgery, Teaching Hospital Hradec Kralove, this surgical method has been carried out since 1999. THE AIM OF THIS WORK: To analyze the long-term results of the Longo's operation. This study has been based on the retrospective documentation analysis complemented by a questionnaire-survey. METHODOLOGY: It is the retrospective documentation study complemented by a questionnaire-survey. The patients received a questionnaire asking questions regarding their subjective feelings and opinions on surgical treatment, as well as on recent status of the illness. Furthermore, the medical documentation was analysed with particular attention to the post-operative period with regard to complications, analgetic therapy need, operation-time, length of the hospital stay and recovery time. RESULTS: Since 1999, the authors have used stapler technique in internal hemorrhoids operations in 71 patients. From this number 65 patients who were operated on at least one year before the follow-up analysis was performed were included into the study. 51 patients completed and gave back the questionnaire. Average following time was 5.5 years. 92 percent of the patients are very satisfied with the Longo's operation. Low rate of complications, small postoperative pain and early recovery are the basic merits of the hemorrhoids operation with use of stapler technique. CONCLUSION: We think of Longo's operation in indicated cases as safe and suitable for the hemorrhoids therapy. PMID- 20586166 TI - [Improving of treatment safety in emergency thoracic surgery]. AB - Authors point out a possibility of improving operative results in thoracic surgery with acute state. They prove it with two groups of patients, where preoperative complications are anticipated. The first group consists of the patients with thorax injury and the second group consists of the patients with relapsing pneumothorax. With a blunt thorax injury is the surgical treatment often performed on blood-soaked pulmonary tissue or on parenchyma affected by ARDS. A necessary stapler suture during an atypical reaction is accompanied by bleeding or air-leak from the resected area. To reinforce the suture, there are used various materials for staplers to utilize a padding effect. Sometimes is necessary to use tissue sealants to prevent the air-leak. Traumacel Stapler Seam Protection meets requirements on the stapler suture reinforcement and, moreover, due to its bactericidal and haemostatic effects helps the tissue healing. PMID- 20586167 TI - [Mobile genetic elements in the epidemiology of bacterial resistance to antibiotics]. AB - The study of the role of mobile elements and mobilization of resistance genes is crucial for understanding the epidemiology of antibiotic resistance. This review summarizes recent data on the insertion sequences, transposons, integrons and plasmids that are involved in the mobilization of bacterial antibiotic resistance genes. PMID- 20586168 TI - [Opportunistic pathogen Candida glabrata and the mechanisms of its resistance to antifungal drugs]. AB - Treatment of not only bacterial but also fungal infections is currently a growing concern. A major reason is the acquisition of multidrug resistance in both prokaryotic and human cells. The multidrug resistance phenotype is a cellular response to the presence of cytotoxic substances in the environment. The basic mechanism of multidrug resistance is overexpression of the membrane proteins involved in the extrusion of toxic substances outside the cell. The resistance mechanism based on the efflux of inhibitors as a result of the overproduction of transport proteins was also observed in some plant and animal pathogens and human tumour cells. The phenomenon of multidrug resistance associated with an excessive and long-term use of antifungals, in particular of azole derivatives, was also confirmed in the yeast Candida glabrata which is becoming a growing concern for health care professionals. Reduced susceptibility to azole derivatives in particular, a high potential for adapting to stressors, and multiple mechanisms of resistance to structurally and functionally unrelated antifungal drugs make the species C. glabrata a potential threat to hospital patients. PMID- 20586169 TI - [Susceptibility of Staphylococcus aureus biofilms to vancomycin, gemtamicin and rifampin]. AB - STUDY OBJECTIVES: To detect biofilm formation in Staphylococcus aureus strains and to determine the minimal biofilm inhibition concentrations (MBIC) and the minimal biofilm eradicating concentrations (MBEC) of vancomycin, gentamicin and rifampin. To compare the MBIC and MBEC with the minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC) data for planktonic Staphylococcus aureus forms that are commonly used in antimicrobial susceptibility testing for the purposes of individualized therapy. PATIENTS AND METHODS: Fifteen S. aureus strains isolated from central venous catheters, intratracheal tubes and wound drainage tubes from the patients of the University Hospital, Bratislava-Stare Mesto were included in the study. Selected virulence factors were characterized. The biofilm formation potential was measured by a modified crystal violet micro-assay. The presence of viable cells biofilm in was tested using 3-(4,5-dimethylthiazol--2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The MIC and MBC of vancomycin, gentamicin and rifampin was tested in planktonic S. aureus forms by the broth microdilution method. The MBIC and MBEC of these antimicrobial drugs for biofilm S. aureus forms were determined by a modified microdilution method. Student's t-test was used for statistical analysis of the results. RESULTS: All of the study strains formed biofilm, with only two of them having a low biofilm formation potential. MTT revealed moderate to high metabolic activity of bacteria biofilm in Vancomycin MICs and MBICs were identical in 80 % of the study strains. Vancomycin MBECs are higher than MBCs in all the study strains, are interpreted as resistance according to the criteria of the Clinical and Laboratory Standards Institute (CLSI) and make the drug unsuitable for use in the treatment. In vitro gentamicin MBICs indicated susceptibility according to the CLSI criteria but gentamicin MBECs were interpreted as gentamicin resistance. Rifampin MICs and MBICs of the study strains revealed susceptibility. Rifampin MBCs were interpreted as susceptibility, but based on MBECs, 13% of the study strains were considered as resistant and 13% of the study strains showed intermediate susceptibility. The differences between gentamicin and rifampin MICs and MBICs and those between MBCs and MBECs of all antimicrobials tested were statistically significant. CONCLUSION: The tested biofilm S. aureus forms showed high MBECs of vancomycin, gentamicin and rifampin, with rifampin only being suitable for therapeutic use. To provide reliable results for individualized antibiotic therapy, it will be needed to test in vitro biofilm formation, to determine MBIC and MBEC of antimicrobial drugs using a standardized method, to interpret the test results in relation to biofilm S. aureus forms and to establish the interpretation criteria for MBIC and MBEC similarly to MIC and MBC. PMID- 20586170 TI - [Antibiotic resistance and biofilm formation in Staphylococcus saprophyticus strains isolated from urine]. AB - Eighty-seven Staphylococcus saprophyticus strains isolated from urine of 87 patients with cystitis were examined in 2005-2009. All strains were tested for resistance to vancomycin, nitrofurantoin, doxycycline, oxacillin, amoxicillin/clavulanate, cefoxitin and sulfamethoxazole/trimethoprim and for biofilm formation by a modified Christensen method. None of the tested strains of S. saprophyticus showed resistance to vancomycin, while 2 strains (2.3 %) were resistant to nitrofurantoin, 9 (10.3%) to doxycycline, 20 (23.0 %) to oxacillin, 6 (6.9%) to amoxicillin/clavulanate, 6 (6.9%) to cefoxitin and 1 (1.1%) to sulfamethoxazole/trimethoprim. S. saprophyticus was detected as the causative agent of cystitis in 0.4 % of 20,375 culture positive urine samples analyzed in our laboratory between 2005 and 2009. Most 67 (77.0%) S. saprophyticus strains were recovered from women, particularly from young women. Biofilm formation was detected in 16 (18.4 %) out of 87 S. saprophyticus strains. PMID- 20586172 TI - Patient flow takes on new importance with health care reform. PMID- 20586171 TI - [Genotyping of viral glycoprotein B (gB) in hematopoietic stem cell transplant recipients with active cytomegalovirus infection: analysis of the impact of gB genotypes on the patients' outcome]. AB - AIM OF THE STUDY: Genetic variation of CMV strains may correlate with their pathogenicity for immunocompromised patients. On the basis of sequence variation in the UL55 gene encoding the most abundant viral envelope glycoprotein gB, CMV can be classified into four major gB genotypes. The aim of the study was the analysis of the distribution of gB genotypes in a cohort of haematopoietic stem cell transplant (HSCT) recipients and of the correlation of genetic polymorphisms with clinical outcomes and manifestation of CMV infection. MATERIAL AND METHODS: Archived DNA isolates from consecutive blood samples of 53 adult allogeneic HSCT recipients with active CMV infection, transplanted in 2004-2005, were used for the genetic analysis. HCMV gB genotyping was performed by restriction fragment length polymorphism (RFLP) analysis and sequencing of the central variable region of UL55. The association of gB genotypes with selected clinical parameters was assessed by multivariate analysis after adjustment for graft donor type, HLA matching and anti-thymocyte immunoglobulin (ATG) therapy. RESULTS: gB1, gB2, gB3, and gB4 genotypes were detected in 30%, 17%, 26% and 4% of the patients, respectively. An atypical gB genotype was found in one patient. Co-infection with two or more gB genotypes was revealed in 17% of the patients. The distribution of gB genotypes did not vary in time, despite the fact that the patients transplanted in 2005 had more severe CMV infection with higher viral loads in the blood than those transplanted in 2004. gB1 was associated with a lower viral load (p = 0.046) and a milder course of symptomatic CMV infection, but with a higher rate of acute graft versus host disease (OR 3.4; p = 0.067). Pancytopenia was less frequent in the patients infected with gB3 (OR 0.09; p = 0.075). In contrast, gB2-infected patients had a worse outcome of CMV infection with a higher rate of organ involvement and were less responsive to antiviral therapy (OR 6.65 and 0.18; p = 0.15 and 0.12, respectively). The prognostic impact of co infection with two or more gB genotypes was not shown. CONCLUSIONS: gB genotype may have an impact on the course of CMV infection and its complications in HSCT recipients. Nevertheless, these results need to be tested on a larger group of patients in the context of genetic variability of other functionally important viral genes. The characterization of viral genetic factors determining CMV pathogenesis will be of relevance to the treatment of patients at high risk of CMV infection. PMID- 20586173 TI - Communication key to improving throughput. PMID- 20586174 TI - Proposed IPPS hinges on accurate documentation. PMID- 20586175 TI - Prepare now for the implementation of ICD-10. PMID- 20586176 TI - Critical path network. Bed capacity project reduces discharge, ED delays. PMID- 20586177 TI - Critical path network. Bay Medical improves ED throughput via ICU. PMID- 20586178 TI - Medicare project focuses on hospital readmissions. PMID- 20586179 TI - MI system leads in effort to improve transitions. PMID- 20586180 TI - [Peculiarities of 5-methylcytosine distribution in eukaryotic genome]. AB - Most of it functions DNA methylation realizes as an integral part of the mechanism of remodeling and modification of chromatin structure. At the same time the global pattern of this complex reaction's net is still to be determined and we are just approaching to studying the mechanisms controlling epigenetic processes of histone modification and DNA methylation. Though cytosine methylation occurs predominantly at CpG sequences of eukaryotic genome, it also takes place at symmetric CpHpG and non-symmetric CpHpH sites (where H-A, T, or C). Various modification efficiency for these three site-specific DNA methylation types is observed depending on their genome localization. Different regions in eukaryotic genome are remarkable for their methylation features: CpG-islands, CpG islands shores, differentially methylated regions of imprinted genes, and regions of non-alternative site-specific modification. Dependence of three canonical types (CpG, CpHpG, and CpHpH) of DNA methylation efficiency on their surrounding nucleotide context is noted. Existence of epigenetic code of DNA methylation, in which these context differences play specific functional role, has been supposed. The present review summarizes main up-to-date data on structural-functional features of site-specific cytosine methylation in eukaryotic genomes. Pathogenesis-related alterations of eukaryotic genome methylation pattern are considered as well. PMID- 20586181 TI - [Organization and regulation of nucleocytoplasmic transport]. AB - Separation of processes of DNA replication and transcription from protein synthesis, which occurs in eukaryotic cells, allows more precise control over these processes. Selective exchange of macromolecules between these two compartments is mediated by proteins of nuclear pore complex (NPC). Receptor proteins of karyopherin family interact with NPC components and transfer their cargos between nucleus and cytoplasm. Nucleocytoplasmic transport pathways are regulated on multiple levels by modulating the expression or function of single cargoes, transport receptors, or the transport channel. These levels of regulation have increasingly broad effects on transport pathways, and affect a wide range of processes, from gene expression to development and differentiation. PMID- 20586182 TI - Two polymorphisms of the FVII gene and their impact on the risk of myocardial infarction in poles under 45 years of age. AB - High levels of coagulation factor VII (FVII) in plasma have been associated with the increased risk of myocardial infarction (MI) in some studies. Both environmental and genetic factors are responsible for different levels of FVII in plasma. In the FVII gene there are two common polymorphisms (-323A1/A2 and IVS7)which are related to the level of FVII. The purpose of this study was to evaluate the influence of these polymorphisms on the risk of acute myocardial infarction in Poles under 45 years of age. We performed a case-control study of 266 patients with the history of MI. All patients had the first incidence of MI before 45 years of age. The control group consisted of 137 healthy individuals older than 45 years. Carriers of the A2 allele (-32341/A2 polymorphism) have a lower risk of MI than noncarriers (OR = 0.40, 95% CI = 0.20 to 0.80). The IVS7 polymorphism was shown not to be related to MI in this study. Our findings suggest that the -323A1/A2 polymorphism of the FVII gene is related to the risk of MI in Polish individuals. We pointed that plasma cholesterol (OR = 1.11, 95% CI = 1.03 to 1.18), arterial hypertension (OR = 3.84, 95% CI = 1.99 to 7.43) and family history (OR = 2.72, 95% CI = 1.57 to 4.73) are significant predictors of acute myocardial infarction. PMID- 20586183 TI - cDNA, genomic sequence cloning and overexpression of glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) from the Giant Panda. AB - GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is a key enzyme of the glycolytic pathway and it is related to the occurrence of some diseases. The cDNA and the genomic sequence of GAPDH were cloned successfully from the Giant Panda (Ailuropoda melanoleuca) using the RT-PCR technology and Touchdown-PCR, respectively. Both sequences were analyzed preliminarily. The cDNA of GAPDH cloned from the Giant Panda is 1191 bp in size, contains an open reading frame of 1002 bp encoding 333 amino acids. The genomic sequence is 3941 bp in length and was found to possess 10 exons and 9 introns. Alignment analysis indicates that the nucleotide sequence and the deduced amino acid sequence are highly conserved in some mammalian species, including Homo sapiens, Mu musculus, Rattus norvegicus, Canis lupus familiaris and Bos taurus. The homologies for the nucleotide sequences of the Giant Panda GAPDH to that of these species are 90.67, 90.92, 90.62, 95.01 and 92.32% respectively, while the homologies for the amino acid sequences are 94.93, 95.5, 95.8, 98.8 and 97.0%. Primary structure analysis revealed that the molecular weight of the putative GAPDH protein is 35.7899 kDa with a theoretical pI of 8.21. Topology prediction showed that there is one Glyceraldehyde 3-phosphate dehydrogenase active site, two N-glycosylation sites, four Casein kinase II phosphorylation sites, seven Protein kinase C phosphorylation sites and eight N-myristoylation sites in the GAPDH protein of the Giant Panda. The GAPDH gene was overexpressed in E. coli BL21. The results indicated that the fusion of GAPDH with the N-terminally His-tagged form gave rise to the accumulation of an expected 43 kDa polypeptide. The SDS-PAGE analysis also showed that the recombinant GAPDH was soluble and thus could be used for further functional studies. PMID- 20586185 TI - [Functional siate of serotoninergic system and the 5-HTTLPR polymorphism of the serotonin transporter gene in patients with schizophrenia]. AB - Blood serotonin concentration is thought to regulate behavior and may be implicated in the development of psychopathological symptoms as well. Serotonin transporter regulates the levels of serotonin by the reuptake of this neurotransmitter from the synaptic cleft. In this study we compare the platelet serotonin concentration and constant V(max) value in patients with schizophrenia and healthy controls with different 5-HTTLPR genotypes. The study included 60 patients and 62 controls. Biochemical parameters mentioned above were associated with a 5-HTTLPR genotype. Carriers of the LL genotype had lower serotonin blood concentration and V(max) compared to genotypes containing one or two copies of an S allele both in patients and controls. The results obtained suggest that the genetic variant may contribute to the state of serotoninergic system. PMID- 20586184 TI - [Downregulation of AKR1B10 gene expression in colorectal cancer]. AB - Colorectal cancer is one of the most common cancers in the world. In our work changes of AKR1B1 and AKR1B10 gene expression levels in colorectal tumors were studied. Their potential diagnostic value was previously shown for several other cancer types. These genes encode aldoso reductases, which belong to the aldo-keto reductases superfamily consisting of enzymes capable to reduce numerous aromatic and aliphatic aldehydes and ketones. They are also involved into retinoid metabolism and cancerogenesis. We have carried out comparative analysis of mRNA levels of AKR1B1 and AKR1B10 genes in paired samples of normal and colorectal tumor tissues using RT-PCR and quantitative PCR. We have shown for the first time the decrease of activity of these genes in colorectal carcinomas. Significant reduction of AKR1B10 mRNA level was detected in the most of tumor samples (88%, 65/74) even at the early stages of malignancy, and in more than 60% of cases this downregulation was much higher than 10 folds. The decrease of AKR1B1 mRNA level was shown in 10% of tumors only. Therefore, we have detected quite different mRNA expression patterns in colorectal cancer for these two structurally similar genes. These data could indicate different functional roles of these two genes in colorectum. The significant decrease of AKR1B10 mRNA in most samples of colorectal cancer could be considered as potential diagnostic marker of this type of cancer. PMID- 20586186 TI - [Association of the polymorphisms of the ERBB3 and SH2B3 genes with type 1 diabetes]. AB - To study the association with diabetes mellitus type 1 we performed analysis of the distribution of frequencies of alleles and genotypes of polymorphic marker rs2292239 of ERBB3 gene, encoding epidermal growth factor receptor type 3 and polymorphic marker rs3184504 of SH2B3 gene, encoding adaptor protein LNK. The study included groups of T1DM patients and unrelated controls of Russian origin. Genotyping was performed using methods of RFLP and real-time amplification. For the polymorphic marker rs2292239 of ERBB3 gene was not found statistically significant associations with type 1 diabetes, while analysis of the distribution of frequencies of alleles and genotypes of the polymorphic marker rs3184504 of SH2B3 gene showed the presence of association with T1DM in Russian population. PMID- 20586187 TI - [Bifunctional role of domain zinc fingers of methyl-DNA-binding protein Kaiso]. AB - DNA methylation in mammals is one of the major epigenetic mark that associates with inactive chromatin state. Methyl-DNA-binding proteins bind methylated DNA and silence gene transcription by recruiting repression complexes. Kaiso is one of the methyl-DNA-binding proteins. It has a domain structure: N-terminal BTB/POZ domain involved in protein-protein interaction and C-terminal zinc-fingers of C2H2 type that bind methylated DNA (mCGmCG) or nonmethylated - TCCTGCNA. Here we show that Kaiso interacts with p120 catenin through zinc finger 2 and 3. This interaction has dual consequences. Firstly, binding to p120 inhibits nuclear import of Kaiso that results in most of Kaiso-p120 complexes becoming cytoplasmic. And secondly, bound p120 makes impossible interaction of the zinc fingers with methylated DNA. These modes of Kaiso modulation by p120 can open attractive perspectives in linking events on cell membrane and changes in nuclear gene expression. PMID- 20586188 TI - [DNA immunization with a plasmid containing gene of hepatitis C virus protein 5A (NS5A) induces the effective cellular immune response]. AB - In spite of extensive research, no effective vaccine against hepatitis C virus (HCV) has been developed so far. DNA immunization is a potent technique of vaccine design strongly promoting the cellular arm of immune response. The genes encoding nonstructural HCV proteins (NS2-NS5B) are promising candidates for vaccine development. NS5A is a protein involved in viral pathogenesis, in the induction of immune response, and probably in viral resistance to interferon treatment. The objective of this study was to construct a DNA vaccine encoding NS5A protein and evaluate its immunogenicity. A plasmid encoding a full-size NS5A protein was produced using the pcDNA3.1 (+) vector for eukaryotic expression system. The expression of the NS5A gene was confirmed by immunoperoxidase staining of the transfected eukaryotic cells with anti-NS5A monoclonal antibodies. Triple immunization of mice with the plasmid vaccine induced a pronounced cellular immune response against abroad spectrum of NSSA epitopes as assessed by T-cell proliferation andsecretion of antiviral cytokines IFN-gamma and IL-2. In in vitro T-cell stimulation experiments, NS5A-derived antigens were modeled by synthetic peptides, recombinant proteins of various genotypes, and phages carrying exposed NS5A peptides. A novel immunomodulator Immunomax showed high adjuvant activity in DNA immunization. The data obtained indicate that the suggested DNA construct has a strong potential in the development of the gene vaccines against hepatitis C. PMID- 20586189 TI - [Cholesterol-modified anti-MDR1 small interfering RNA: uptake and biological activity]. AB - Small interfering RNAs (siRNA) are considered to be potent agents for specific gene silencing, but troubles in delivery of siRNA into cells limit their biomedical application. An accumulation of siRNA coupled with cholesterol residue at the 5'-end of the "passenger" strand (chol-siPHK) was investigated in HEK293, HepG2, SC1, and KB-8-5 cells. In the absence of a transfectant levels of both unmodified and chol-siRNAs were very low, whereas transfectant substantially increased transfection rate in all cell lines; in HEK293, SC1, and KB-8-5 cells transfection efficiency for the chol-siRNA being higher than that for the corresponding siRNA. Multiple drug resistance phenotype reversing activity of anti-MDR1-siRNAs targeted to the 557-577 region of MDR1 gene mRNA was investigated in KB-8-5 cancer cells. The chol-siRNA induced cancer cells' death in the presence of vinblastine doses tolerated before more effectively than the conventional siRNA did. PMID- 20586190 TI - [Sop proteins can cause transcriptional silencing of genes located close to the centromere sites of linear plasmid N15]. AB - Stable inheritance of bacterial chromosomes and low copy number plasmids is ensured by accurate partitioning of replicated molecules between the daughter cells at division. Partitioning of the prophage of the temperate bacteriophage N15, which exists as a linear plasmid molecule with covalently closed ends, depends on the sop locus, comprising genes sopA and sopB, as well as four centromere sites located in different regions of the N15 genome essential for replication and the control of lysogeny. We found that binding of SopB to the centromere can silence centromere-proximal promoters, presumably due to subsequent polymerizing of SopB along the DNA. Close to the IR4 centromere site we identified a promoter, P59, able to drive expression of phage late genes encoding the structural proteins of virion. We found that following binding to IR4 the N15 Sop proteins can cause repression of this promoter. The repression depends on SopB and became stronger in the presence of SopA. Sop-dependent silencing of centromere-proximal promoters control gene expression in phage N15, particularly preventing undesired expression of late genes in the N15 prophage. Thus, the phage N15 sop system not only ensures plasmid partitioning but is also involved in the genetic network controlling prophage replication and the maintenance of lysogeny. PMID- 20586191 TI - [Overexpression of genes encoding tRNA(Tyr) AND tRNA(Gln) improves viability of nonsense mutants in SUP45 gene in yeast Saccharomyces cerevisiae]. AB - The variety of mechanisms providing viability of organisms bearing nonsense mutations in the essential genes is unknown at present. In yeast Saccharomyces cerevisiae nonsense-mutants containing premature stop-codon in mRNA of the essential SUP45 gene were obtained. These strains are viable in the absence of mutant suppressor tRNA, therefore it is supposed that there are alternative mechanisms providing nonsense-suppression and mutants viability. Analysis of transformants obtained by transformation of strain bearing nonsense-mutant allele of SUP45 gene with multicopy yeast genomic library revealed three genes encoding wild type tRNA(Tyr) and four genes encoding wild type tRNA(Gln) that improve nonsense-mutants viability. Moreover, overexpression of these genes leads to the increase in the amount of full-length eRF1 protein in cell and compensates nonsense-mutants sensitivity to high temperature. Probable mechanisms of tRNA(Tyr) and tRNA(Gln) influence on the increase of viability of nonsense mutants in SUP45 gene are discussed in this work. PMID- 20586192 TI - [Generation of transgenic animals, expressing alpha- and beta-chains of autoreactive TCR]. AB - Transgenic animal studies has become a key approach for gene function analysis as well as for modeling of different human diseases, including autoimmune diseases caused by activation of T-lymphocyte clones whose TCRs possesses high affinity for syngeneic MHC molecules. In this study we cloned genes, encoding alpha- and beta- chains of autoreactive TCR of hybridoma 7, specific for syngeneic MHC class II molecules A(b). Amplified DNA fragments, containing rearranged genomic DNA of alpha- and beta-chains of hybridoma 7 were cloned into special cassette vectors, containing natural promoter and enhancer elements for direct expression of genes encoding TCR alpha- and beta-chains in T-lymphocytes of transgenic animals. Using this cassette vectors we generated animals in which most of peripheral T lymphocytes carry alpha-chain, as well as animals with expression of beta-chain transgene of autoreactive TCR. Obtained animals may serve to explain a number of intrathymic selection processing features and T cell maturation as well as to serve as experimental models for development of new approaches to therapy of autoimmune diseases. PMID- 20586193 TI - [A pocket pRb mutation induces the increase in its affinity to E2F4 coupled with activation of muscle differentiation]. AB - Co-ordination of proliferation and differentiation in cells committed to muscle fate requires the interaction of the retinoblastoma gene product (pRb) with transcription factors of the E2F family. pRb has different affinities for distinct E2Fs, however, the mechanism involved in pRb-E2Fs interaction has not been completely investigated. We have found that pRb carrying a small deletion at the end of the T antigen binding region (deltaS/N), and unable to interact with large T antigen, could induce acute cell cycle block, stable prolongation of the cell cycle in G0/G1 and G2/M phases and suppression of the growth of tumor cells. The deltaS/N showed increased affinity for E2F4, bound hyperphosphorylated forms of E2F4 and induced its nuclear compartmentalization. The ability of deltaS/N to form complexes with E2F4 on DNA was associated with an increase in formation of "free" E2F4 and transsuppression of the specific reporter through preferential binding to E2F4 but not t o E2F1. Stable expression of deltaS/N in multi-potent fibroblasts promoted early muscle commitment. The results obtained suggest that a mutation in the T antigen binding region may increase in affinity of the pRb for E2F4 combined with activation of muscle differentiation. PMID- 20586194 TI - Identification of the transactivation domain of the human FHL3. AB - Four and a half LIM domain protein 3 (FHL3) has the transactivation and repressor activity, and plays important roles in regulating the expression levels of various genes. In this study, FHL3 was proved to possess the auto-activation ability when constructed into the pGBKT7 plasmid (a GALA DNA-binding domain (BD) cloning vector of the yeast two-hybrid system) and transformed into yeast Y190 cells. To determine the transactivation domain of FHL3, five mutants were constructed by sequentially deleting each LIM domain of FHL3 and then inserting them into the pGBKT7 plasmid. After being transformed into yeast Y190 cells, expression levels of the mutants were identified by Western blot analysis. The beta-galactosidase assay showed that the mutant without the fourth LIM domain (LIM4) lost the auto-activation ability. Further investigations on the mutants with deleted first or second zinc finger of LIM4 confirmed that the second zinc finger motif in LIM4 was responsible for the auto-activation of FHL3. PMID- 20586195 TI - [Atomic force field FFsol for calculation of molecular interactions of in water environment]. AB - Detailed calculations of protein interactions with explicitly considered water takes enormous computer time. The calculation becomes faster if water is considered implicitly (as a continuous media rather than as molecules); however, these calculations are much less precise, unless one uses an additional (and also volumes) computation of the solvent-accessible areas of protein atoms. The aim of our study was to obtain parameters for non-bonded atom-atom interactions for the case when water surrounding is considered implicitly and the solvent-accessible areas are not computed. Since the "in-vacuum" interactions of atoms are obtained from experimental structures of crystals and enthalpies of their sublimation, the "in-water" interactions of atoms must be corrected using solvation free energies of molecules, which can be obtained from the Henry constants. Taken 58 structures of molecular crystals and thermodynamic data on their sublimation and solubility, we obtained parameters for "in-water" attraction and repulsion of atoms typical of protein structures (H, C, N, O, S) in various covalently-bonded states, as well as parameters for electrostatic interactions. All necessary for calculations parameters of covalent interactions have been taken from the ENCAD force field, and partial charges of all atoms of separate molecules of a crystal have been obtained from quantum-mechanical calculations. The sought parameters of the "in water" van der Waals and electrostatic interactions were optimized so as to achieve the best description of equilibrium crystal structures and their sublimation and solvation at the room temperature. With the optimized parameters, the average error in calculation of the effective cohesion energy of molecules in crystals was less than 10% both in the "in-vacuum" and "in-water" cases. PMID- 20586196 TI - [Amplification of intermethylated sites experimental design and results analysis with aims in silico computer software]. AB - Amplification of intermethylated sites (AIMS) is a powerful tool for differential methylation screening of genomes. Its applications have nevertheless been limited until recently for the absence of systemic approach to AIMS experimental design and of appropriate computer software for the analysis of AIMS results. We have developed AIMS in silico computer suggestion tool capable of predicting possible experimental outcomes, which assists in designing AIMS experiments depending on the research aims and available instrumentation, and in analyzing experimental results from the point of view of genomic locations of the DNA fragments under study. With AIMS in silico we have characterized qualitatively and quantitatively AIMS products obtainable under different conditions; to ease experimental design we demonstrate AIMS products hierarchical structure. We discuss examples of designing AIMS experiments and results analysis as well as possible relative to AIMS alternative approaches to differential methylation screening. AIMS in silico computer software is intended to standardize AIMS applications and to turn it into one of the principal approaches towards cancer epigenomes studies as well as towards diagnostics in oncology, including early screening. PMID- 20586197 TI - [Applicability of coexpression networks analysis to anticancer drug targets discovery]. AB - Identification of proteins that can be therapeutically targeted is an important problem in molecular biology. Transcriptomics approaches such as coexpression network analysis have been previously proposed as tools facilitating drug targets discovery. To assess whether coexpression network analysis is applicable to prediction of novel anticancer drug targets, we compared known targets of 103 antineoplastic drugs with those of 776 drugs irrelevant to cancer in terms of their position in the coexpression network of glioblastoma--one of the most malignant human cancer types. Affymetrix GeneChip expression data for 93 glioblastoma surgery samples were analyzed. We were able to identify coexpression modules associated with such processes as proliferation, immune response, neurotransmission, ATP synthesis, extracellular matrix formation and others. Anticancer drug targets were fourfold over-represented in the coexpression module associated with cell proliferation and mitosis relative to the other modules. Network connectivity of drug targets within the mitotic module was found to be highly correlated with the number of anticancer drugs acting upon them. Our results support the hypothesis that hubs in the mitotic module represent potential anticancer drug targets, and confirm applicability of coexpression network analysis to anticancer drug targets identification. PMID- 20586198 TI - [Comparison of 2D analysis and bioinformatics search efficiency for colon cancer marker identification]. AB - Modification of 2D analysis protocol was developed, based on preliminary removal of major cellular proteins by extraction with buffer saline and elimination of high molecular weight proteins by gel filtration. This approach allowed identification of 12 proteins with increased expression levels in tumors versus normal tissues. Increase in expression levels of the eight proteins in colon tumors was discovered for the first time. We performed comparison of marker search efficiency by 2D analysis and SAGE in a control panel of 19 putative colon cancer markers, discovered by us previously and at the same time independently identified by other authors. Results of 2D analysis of control panel completely coincided with published data, as compared to search in SAGE database, which allowed identification of only one third of markers. PMID- 20586199 TI - [Infantile malnutrition represented by mothers of low weight children]. AB - Working with mothers of low weight (LW) children in a Public Health Unit in Rio de Janeiro, we tried to understand their social representations (SR) and health practices in order to influence the search for treatment and therapeutical observance. An explorative study based on the theory of Moscovici, included accounts from the group of mothers and 20 in-depth interviews, divided in two groups: 10 mothers whose children received clinical release and 10 mothers with children in medical treatment. We made a thematic content analysis. The study disclosed that SR of infantile malnutrition is associated to the idea of death, the end of life of their children. These mothers prefer to speak of LW, considered as transitory and recoverable by maternal care and medical treatment. The results of this work indicate how much the recognition of consensual popular knowledge, assists the good relationship with health services and therapeutical observance. PMID- 20586200 TI - [The integrality in daily work in family health strategy]. AB - This work is part of a research for evaluation of the Expansion and Consolidation of Family Health Program (PROESF). This is a study with a qualitative approach, developed in a unit of family health seen as successful experience in relation to the organization to integral care, located in a city of medium size. This article tried to approach the integrality of care with an emphasis on the team work, to identify in the daily practices, the potential and limits to enable the integration. The instruments used were semi-structured interviews with eight members of staff and observations diary recorded in a field. It was verified the existence of alternative practices that escape from the traditional model, considered as completeness potentiators. However obstacles were also highlighted to the integrality such as difficulty of access for users to certain specialties and lack of reception in the service. PMID- 20586201 TI - [Cytopathological alterations and risk factors for uterine cervical neoplasm]. AB - The aim of the present study was to verify the occurrence of citopathological alterations and risk factors of Uterine Cervical Neoplasm in women attended by SUS--the Public Healthcare System--in a district situated in the North of Parana State, Brazil from 2001 to 2006. It was a descriptive transversal observational study. The data collection consisted in collection of test results from medical records and interviews. It was achieved 6.356 tests and, 1.02% (65) of the women examined presented alterations. From the tests made 4.869 (70,8%) were from women aged between 25 and 59 years. And 38,5% of the tests presented Cervical Intraepithelial Neoplasm (CIN) I, 32,3% CIN II, 18,5% CIN I and Human Papiloma Virus (HPV). It was interviewed 25 women from the total sample. Most of them presented a risk factor as: smoking habits, sexually transmitted diseases, use of hormonal contraceptive, number of sexual partners, early sexual intercourse. This study concludes that is required educative and more effective actions in order to reduce the alterations, meanly among teenagers. PMID- 20586202 TI - [The perceptions of the health professionals at a hospital about the violence against women]. AB - This qualitative study aimed at finding out the perceptions of health professionals about the assistance to women living in a violent situation. The scenery was a teaching hospital of southern Brazil. The participants were 12 health professionals from the obstetric and emergency units. The data were collected by semi structured interviews started by a short story in April to May of 2008. The information was organized and categorized and subject to thematic analysis. The results showed two categories: the dialogue as a facilitator instrument to identify the violence and their referrals and the complexity of the phenomena and their implications to the assistance. We pointed out the necessity of to create spaces of the responsibility of agencies devoted to training human resources in health and health services. It is in order to form multiprofessional team that discuss and implements the policy care to women living in a violent situation. PMID- 20586203 TI - [Perceptions of nurses about leadership]. AB - This study aimed at ascertaining the perceptions of nurses facing the use of managerial leadership as a tool in their work process. This was a qualitative study of descriptive and exploratory type, conducted with eleven nurses from a large hospital in the southern region of Rio Grande do Sul, Brazil, during the months of February and March 2008. For data collection were used semi-structured interviews and focus group. The content analysis was chosen as a technique for processing the data, resulting in two categories: meanings attributed to the leadership and authority versus authoritarianism. It was noticed that even the leadership offering advantages in nursing work, are still great the difficulties to understand it and, especially, to put it into practice, making it necessary to create programs and strategies to improve the performance of the leadership as a nurses managerial instrument. PMID- 20586204 TI - [Health care given to patients with violence situations: conceptions of professionals in basic health units]. AB - The following study aimed at analyzing the conceptions of basic health units' professionals on the service rendered to users with violence situations, within their different manifestations. It is a qualitative research conducted with nurses, doctors, nursing technicians, and communitarian health agents through semi-structured interviews. The set of data was collected from October 2007 and March 2008 in Porto Alegre, Rio Grande do Sul, Brazil, and analyzed through theme analysis. The professionals have a role in identifying situations of violence and in elaborating intervention strategies aiming users' welfare through the recovery of physical and mental health. The break of the violence assistance net, lack of security, lack of capable professionals, and inadequate infrastructure are some of the factors that jeopardize the service. The results might support the elaboration of public policies that help the identification, gathering and assistance to individuals in violence situations. PMID- 20586205 TI - [National curriculum guidelines: perceptions of academics about their training in nursing]. AB - The objective was to study the perceptions of nursing students about their education considering the National Curriculum Guidelines. This is an exploratory study with a qualitative approach, data were collected in March 2007 through semistructured interviews with ten senior students of the undergraduate course at the Federal University of Rio Grande do Sul, Brazil, and all study participants signed an Informed Consent. The data were analyzed using content analysis. The results showed an understanding of the students for their training and their close relationship as study participants with higher education, national curriculum guidelines for nursing, teaching project of the course, the profile of the egress and the curriculum. We conclude with an emphasis on curriculum and pedagogical project of the course as relevant to proper training, integrated and harmonized with the National Curricular Guidelines for Nursing. PMID- 20586206 TI - [Risk factors for coronary artery disease in patients admitted in hemodynamics unit]. AB - Transversal study aiming to evaluate the predominance of risk factor (RF) regarding to coronary artery disease (CAD) in patients submitted to cardiac procedures in hemodynamic unit. The study encloses 302 patients of 62 +/- 11 years-old, 270 (89%) predominantly white and 172 (57%) male. The most prevalent RF was 227 (75%) sedentism, followed by 220 (73%) arterial hypertension, 150 (50,5%) dyslipidemia, 87 (29%) obesity, 81 (27%) diabetes mellitus, 77 (25,5%) smoking, 67 (22%) alcohol and 15 (5%) diet poor of fruits and vegetables. The correlation was not relevant between the quantity of RF and its variables: scholarship, income, age, marital status, professional activity and gender in addition to the quantity of procedures submitted, comparing those with five or more RF for CAD; however there is a positive connection that reinforces the importance of strategies towards to reduce or remove modifiable RF. PMID- 20586207 TI - [Severity of the intoxications by cholinesterase inhibitor insecticides registered in the northwest of the state of Parana, Brazil]. AB - This article has as objective the discussion of the severity of intoxications by cholinesterase inhibitor insecticides, which happened in the Northwest of Parana, Brazil, starting from an exploratory descriptive study with retrospective analysis of epidemiological data sheets of the Intoxications Control Center in the University Hospital of Maringa, Parana, Brazil, referring to patients intoxicated from January, 1994 to December 2005. 529 cases were analyzed, 168 (31,7%) for organophosphates and 167 (31,5%) for carbamate. The suicide attempt represented 257 cases (48,5%), the occupational exposure 140 (26,5%), and the accidental 124 (23,5%). Comparing the number of severe intoxications and deaths, it was verified from 100% of deaths to cases severe occupational exposure, 20% for the suicide attempt and 7,5% deaths for the accidental intoxications classified as severe. The high incidence of serious intoxication and mortality suggest preventive strategies in respect of the usage of the insecticides, aiming to restrict the indiscriminate access to these powerful toxic agents. PMID- 20586208 TI - [Humanization: social representations of a children's hospital]. AB - This study aims at investigating the architectural and built environment aspects involved in the humanizing process in a pediatric hospital and its influence to the recovering of the hospitalized child. Based on the Social Representation Theory, a structural analysis was carried out, using free association of words and a semi-structured questionnaire for data collection. The study was carried out in a public hospital in Rio de Janeiro, Brazil, and the results presented refer to the representations produced by 75 people accompanying hospitalized child. As central nucleus appears "consultation", while "reform", "medicines", and "organization" and "affection" appear as peripheral system. For this group humanization seems to be strongly connected to the right to health and access to care. Nevertheless, aspects keep the balance of the quality of care, which are enrolled under humanization, are not neglected. The results allow providing recommendations to improve the contemporary hospitals architectural programs and the quality of care. PMID- 20586209 TI - [Maternity in adolescence: a dream come true and future expectation]. AB - This qualitative study aimed at describing the reasons that motivate an adolescent to get pregnant and her expectations about the future after the child's birth. Symbolic Interactionism was used as theoretical framework and Grounded Theory as the methodological one. Eight adolescent mothers aged between 15 and 19 years who lived the experience of caring for their children took part in the study. Data collection tools were observant participation and semi structured interviews. Data analysis revealed that becoming a mother is an experience that might be desired and even planned. Furthermore, data showed that after the child's birth, the adolescent continues to have expectations of self realization in order to provide a better future for herself and for her child, as revealed by the categories: Making a dream come true and Having expectations about the future. The full understanding of this experience will contribute to the practice of all professionals that provide assistance to pregnant and adolescent mothers at different levels of healthcare. PMID- 20586210 TI - [The senses of health education for community health agents]. AB - The study aimed at identifying the social representation of health education built by communitarian health workers. It was developed with 119 communitarian health workers in the city of Joao Pessoa, Paraiba, Brazil. Data were collected by the test of free association of words, questionnaires and interviews and analyzed by different methods and techniques. The results show: guidance, prevention and care as the centerpiece of representations. The peripheral: important, be prepared to guide, conduct, guidelines, professional, among others. The social representation of health education is structured in two levels: one aimed at informing the general public, another for professional training. PMID- 20586211 TI - [Defense pact on health: disclosing the users' rights through action research]. AB - We objective to discuss the Users' Rights Booklet of the Health Unified System with patients and family members who had looked for attendance in public hospital service. One has chosen the action research, a qualitative and constructive method, which takes into account collective participation and planned action for changes of situations. The data were collected along with the research participants' discussions by means of weekly meetings throughout 2007. The codified speeches were analyzed and resulted in three themes: rights and duties of healthcare users; qualification of health professionals; receptivity to healthcare users. The users' rights booklet consists of an important means for citizens to know their rights of access to the healthcare system, allowing them to contribute in a critical and co-responsible way to discussions and actions in favor of a better healthcare system. PMID- 20586212 TI - [Perception of students on the elderly and their duties: the case of the health]. AB - This is a retrospective study which aimed at examining college students' perceptions about the elderly and their rights, and to investigate knowledge about the elderly rights. Participated in this study 63 students from different courses (both sexes) in the academic realm. We collected information in a semi structured interview focused on issues pertinent to the rights of the aged and the elderly Data were analyzed with the technique of thematic content analysis. The results are presented in categories under the Constitution are interpreted Federal Civil Code and the National Policy for the Elderly, in particular the rights to health. The results showed negative perceptions of students about the elderly and little knowledge about the rights of the elderly, particularly the larger, such as receiving special medication, be treated primarily in hospitals, do not suffer from embarrassment in public health services, right to full health, among others. PMID- 20586213 TI - [Perception about the nursing practice in the psychosocial care centers]. AB - The practice of nursing in the psychosocial care centers in mental health is something made in the institutions daily from established interactions among professionals, patients, and the patient's family. This research is somewhat exploratory and has a qualitative approach. It aims to know the daily practice of professionals from Psychosocial Care Centers on daily practice of the nurse in this kind of work. The collected data were made by means of-semi-structured interviews. From the thematic analysis of the data, two themes appeared: the nurse establishes the first contact with the patients; that is, the nurse is the link between doctors and patients. The results show that the practice of nursing in mental health searches to construct inventive actions, establish affective ties, welcome the patients, and contradict the different way by which some uncommon people are seen the "insane" as a threat. It is a practice that emphasizes the meaning of life production, that is, the increase of the patient's capacity to establish social exchanges, giving him/her greater autonomy. PMID- 20586214 TI - [Health-related quality of life before and six months after coronary artery bypass graft surgery]. AB - Coronary artery bypass grafting (CABG) surgery aims at offering a better health related quality of life (HRQL), relieving symptoms and increasing survival. The objectives were to compare HRQL before CABG and six months after it and to evaluate its relation concerning participants' age, sex, schooling and marital status. Descriptive and longitudinal study which used the SF-36 to evaluate HRQL. Among the 54 subjects, 53,7% were men, 66,7% of them were married, their average age was of 57,3 +/- 9,7 and their schooling of 5,7 +/- 4. After CABG, the scores of the domains of the SF-36 varied from 62 to 74,2 being the previous interval from 17,1 to 58,1. Men showed a better evaluation towards HRQL before and after CABG than women, but the differences were only statistically significant for General Health and Bodily pain. No association between HRQL, schooling and marital status was stated. In conclusion, the CABG improved participants' HRQL. PMID- 20586215 TI - [Social representations of the relationship between the nursing assistant and the user in the Family Health Program context]. AB - Nursing professionals have themselves held liable for the "art" of take care of the users and are the ones who dedicate the major part of their time to them. The aim of this study is to understand the relationship between the nursing assistant and the user expressed by the social representations of the touch act by these professionals in the Family Health Program context. The qualitative-quantitative research involved 25 nursing assistants. The instruments utilized were: free word association, interview, and questionnaire. It was observed that the touch represents possibilities of approximation between the professional and the user as it helps in the user's cure and humanizes the relationship. PMID- 20586216 TI - [Social representations of complex social environments through drawings and texts]. AB - The objective of this work was to observe representations of complex social environments through drawings and texts. We adopted Moscovici's theory, which supposes that the social representations phenomenon is a modern and democratic societies' manifestation. To overcome existing constraints/unequalities, we adopted drawings as a means of expression. We asked secondary students, self defined as African-Brazilians, Mixed people and Whites, to drawn the classroom. The material was analysed according to manifest themes. There was statistical diferentiation on objects, spatial perspectives, teacher colleagues and student. Among high academic performer African-Brazilians we noticed more references to colleagues and conflict/negotiation with teachers. PMID- 20586217 TI - [A view about the interface hospital work and the environmental problems]. AB - This study aimed at verifying how the ecologic reflexivity appears in the context of hospital work and its influence on the workers' performance. Research of qualitative approach, carried out with hospital workers of a public institution. The data were collected by means of a document analysis, field observation and individual and group interview. The data revealed that the worker has a distant relation with the environmental issue, and the regulation of the management of solid residues is the main topic to approach the issue. The development of effective actions of environmental preservation by the hospital worker, the adoption of this question is related to the adoption of this question as an institutional policy, thus this subject should be approached in the permanent education process of the workers, based on serious ethical consideration. PMID- 20586218 TI - [Strategies for teaching the critical thinking abilities in nursing]. AB - This study aimed at characterizing the teaching strategies applied to nursing in order to develop critical thinking skills. An integrative review was elaborated on the Web of Science and Cumulative Index of Nursing and Allied Health Literature (CINAHL) data base, with the descriptors critical thinking, nursing and teaching from 1987 to 2008. The sample comprised 64 articles and the analysis provided the identification of 27 strategies for teaching critical thinking in nursing. Among those, the most referred to were questioning, case study, online teaching and interactive learning, concept map and teaching based on problem solving. Different strategies described in the study revealed a wide range of possibilities which can be applied to teaching and to clinical practice. It was concluded that the development of the critical thinking skills through these teaching strategies can help nursing students to be more critical and reflexive. PMID- 20586219 TI - [Unit of hemodynamics: the production of the knowledge]. AB - This study aimed at doing an integrative review that has as objective to investigate what has been published on nursing in hemodynamic in the following data bases: Scientific Electronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (MEDLINE), Latin American and Caribbean Health Sciences (LILACS), and Nursing Database (BDENF); with the descriptors: Enfermagem and Hemodinamica and Nursing and Hemodynamics. The data indicate that the studies in his majority were developed by nurses, and made a list to the presence of nursing, there were still boarded aspects made a list to the reprocess of catheters and health of the professionals of nursing. Nevertheless, it is noticeable that the publication of works connected with the thematic of hemodynamic is limited. However, they demonstrate the predominance of inquiries and reports making a list to the aspects of the presence of nursing in this sector which may represent the necessities and the problems that permeate the work. PMID- 20586220 TI - [Collective health in the ecosystemic perspective: a possibility of actions of the nurse]. AB - The understructure of the collective health as looking for strategies of protection to the environment also develops a practice of ecosystemic conscience. The ecological practices recognize the right of the human being of living in a healthy and appropriate environment, and being informed about the risks of the environment regarding the health and his welfare. The aim of this present work is to stimulate a reflexive-theoretically discussion on the adoption of the ecological urbane practices in communities and the relation with the collective health and to glimpse insertion possibilities of the actions of the nurse in this space. The conversations actions, a stimulative discussion and approximation of the nurse with the habitat of the human, are able to find reciprocity in the collective health and to the ecosystemic approach. The respect his beliefs and to his knowledge in relation his necessities in health, can come across, objectively, in the promotion of the ecological conscience and of the collective wish turned to the citizenship. PMID- 20586221 TI - Challenges and opportunities in graduate nursing education by distributed learning in Canada and Brazil. AB - In this paper, the authors share their experience related to graduate nursing programs offered by distributed learning (DL) in Canada and Brazil. Although degrees offered by DL are often the subject of criticism, the authors' experience has been that learning outcomes have been very good. Nevertheless, a number of challenges and opportunities have been encountered including those associated with flexibility of the program, delivering practice courses at a distance, facilitating interaction, faculty workload and preparation and student support, Newer technologies that may assist in this effort are identified. Despite the challenges encountered, students rate the program highly and ongoing efforts are underway to ensure excellence of such flexible innovative graduate programs in nursing. The authors argue that despite the challenges, DL programs offer high quality graduate education that meets the needs of many nurses. PMID- 20586222 TI - [Changing in process that involves rest scales of nursing assistant]. AB - Describe the implantation of a new process of management of the nursing assistant rest scale of a hospitalization unit of a universitarian hospital. It is presented the reality before the proposal, when the rests were distributed along the week; the reasons that took to the proposition of the new method and the working of the new scale, with rests in weekends and holidays. Among the benefits already seen include: bigger number of professionals working during the days of bigger work flow; more time of leisure of the workers with their families; bigger personal integration and professional of the group; scales organized for a year, which allows the employee plan his vacation, rests and studies; and bigger satisfaction with the work, with the new scale being considered a professional conquest. PMID- 20586223 TI - Assessment of environmental and socio-economic stress. AB - Since long, socio-economic status, often expressed as an index, is known to correlate with health outcomes like behavioural problems. We constructed a new index that encapsulated not only economic and social but also environmental stressors (ESES), using data of the German Health Interview and Examination Survey for Children and Adolescents, a nation-wide representative surveillance of 17,641 participants aged between 0-17 years. Different factors were selected to account for socio-economic stress (low parental education, low household income, low occupational status of the householder), domestic stress (living in large cities, exposure to tobacco smoke at home, crowded housing, mouldy walls), and prenatal stress (maternal smoking during pregnancy, drinking alcohol during pregnancy). Prior to the calculation of ESES, the different factors were multiplied by weights which were estimated by multivariate linear regression on a number of health outcomes. ESES was then used to predict emotional and social problems (SDQ scores). The resulting ORs were compared with those obtained for an established socio-economic index (SEI). ESES was superior to SEI as it could more clearly identify children and adolescents with emotional or social problems. Different types of stressors (i.e. socio-economic stress, domestic stress and prenatal stress) contributed independently to emotional and social problems. PMID- 20586224 TI - Association of very high Hungarian rate of preterm births with cervical incompetence in pregnant women. AB - BACKGROUND: Maternal cervical incompetence in pregnancy (CIP) showed an association with a higher rate of preterm births. The objective of this study was to determine the prevalence of CIP in Hungarian pregnant women, to determine the rate of preterm birth, and to check the preventive efficacy of preterm births due to CIP by therapeutic cerclage or bed rest alone. METHODS: Analysis of the population-based large data set of 38,151 newborns (without any defects) of the Hungarian Case-Control Surveillance System of Congenital Abnormalities (HCCSCA), born during 1980-1996, i.e. 1.8% of Hungarian newborns. Prospective cohort analysis based on medically recorded variables of CIP, birth weight and gestational age. RESULTS: A total of 2,795 (7.33%) newborns born to mothers with CIP. The newborns of mothers with CIP had a shorter gestational age at delivery (39.0 wk) and higher rate of preterm birth (11.1%) than the Hungarian reference sample without CIP (39.4 wk and 9.0%). Of 2,795 pregnant women with CIP 1,112 were treated by cerclage, while 1,683 with bed rest alone. The mean gestational age was shorter both after therapeutic cerclage (39.2 wk) and particularly bed rest alone (38.9 wk). The rate of preterm births was 9.1% and 12.7% after therapeutic cerclage and bed rest alone. CONCLUSIONS: CIP is very frequent in Hungary probably due the extremely high number of previous induced abortion performed by dilatation and curettage method. CIP associates with an increased risk for preterm births; however, this increased risk was reduced by bed rest alone and mainly by therapeutic cerclage. PMID- 20586225 TI - Short life expectancy and metabolic syndrome in Romanies (gypsies) in Slovakia. AB - The aim of this review is to explain short life expectancy in Romanies. Romanies represent the second largest minority in Slovakia (about 7%). Most of them exist on the fringes of the majority society. Their general situation worsened after the fall of communism in 1989. In a market oriented society the unemployment of Romanies further increased due to their poor education and lack of skills. Romany general health is substantially worse than that of the majority population: They have high prevalence of communicable diseases due to poor sanitary and living conditions. Furthermore, epidemiological and metabolic studies revealed in Romanies high prevalence of obesity associated with increased cardiovascular risk. There is no explanation for this seemingly paradoxical phenomenon, in a population living in poor economic conditions. It is possible that in the course of the many generation-long migration from India to Europe, pregnant Romanies and their fetuses sufferred excessive nutritional deficiency. This might have induced adaptive metabolic and genetic changes aimed at optimum utilization of scarce food supply. There is a hypothetical possibility that in them "thrifty gene" was formed. Arrival of Romanies to Europe resulted in somewhat better nutrition, along with sharply reduced physical expenditure. The consequence is a metabolic syndrome with type 2 diabetes and increased cardiovascular mortality. Such unique metabolic feature in Romanies will undoubtedly stimulate further research in molecular biology that may ultimately clarify the role of "thrifty genes". PMID- 20586226 TI - Similarities and differences between smoking and non-smoking ten-year-old children in primary schools. AB - BACKGROUND: For the majority of smokers, smoking is related to other forms of risk behaviour, especially poorer eating habits. The primary preventive educational programme "No smoking is a norm" focuses on children of younger school age (under 10 yrs), enables comparison and statistical evaluation of whether there are any differences (and which) between ten-year-olds with various smoking experiences, with special attention paid to their exposure to the influence of smokers, and their eating habits. METHODS: Analysis of data gained from a questionnaire compared groups of boys and girls, smokers and non-smokers, and children from families with no smokers, occasional smokers, and frequent smokers. Statistical significance of the differences was tested in the EPI INFO programme by means of the chi2 test. RESULTS: From 1,082 children, almost one quarter (22.9%) have already tried smoking, boys more frequently (25%) than girls (19%) (p < 0.05); and almost 7% smoked repeatedly. The household is the most frequently stated environment for accessing cigarettes in children: 51% of children are given cigarettes by their parents, siblings, grandparents or other relatives, another almost 17% take cigarettes themselves from unprotected stock. From 246 children who have smoked, more than one third were offered cigarettes by their friends, and some (4%) even bought them. Children with smoking experience more often come from smokers' families and more often have smoking siblings and friends who offer them cigarettes. Children claimed to have consumed alcoholic drinks over the past month, repeatedly smoking more often than those with one attempt (aprox. 81% vs 58%) and never smokers (32%). Smokers also more frequently ate salty snacks such as crisps, sausages, and fast foods. The circumstance of whether there are smokers in the child's household or not significantly influenced children's opinions on the smoking of men/boys and women/girls (fewer critics and more admirers in smokers' families), selection of friends, availability of cigarettes, and smoking behaviour of the children. CONCLUSION: The examination of a cohort of ten-year-olds in a semi-longitudinal study confirmed the growing trend of experimenting with smoking. Strong relations to smoking behaviour in families were identified--such that influence a more tolerant approach to parents' smoking, selection of smoking or non-smoking friends, more frequent consumption of alcohol and salty snacks. PMID- 20586227 TI - Social will for tobacco control among the Hungarian public health workforce. AB - BACKGROUND: More than 1 in 5 deaths in Hungary can be attributed to tobacco smoking. The role of the public health agency in responding to and ameliorating the tobacco epidemic in Hungary has been, until now, unexplored. This paper explores the social will of the public health agency workers to adopt tobacco control measures. METHODS: 269 Hungarian public health workers throughout Hungary completed an electronic survey on the types of programs offered by the public health agency, the perceived level of responsibility to reduce tobacco use, and the social will of the agencies to curb tobacco use. Multivariate analyses were performed to estimate factors which contribute to the social will to curb tobacco use. RESULTS: 48% of public health workers in Hungary report that it is absolutely important for local public health agencies to offer tobacco prevention and cessation programs, but only 3% indicate that they have earmarked funds to support anti-tobacco programs. Most workers favor more programs and policies to curb tobacco use in Hungary, such as taxation (67%) and banning smoking in restaurants (81%) and confined sporting events (93%). Factors positively associated with a stronger social will for tobacco control included being a former or never smoker (versus a current smoker) (p < 0.001) and being middle age (40-49, p = 0.04 and 50-59, p = 0.01) (versus being under the age of 30). CONCLUSION: Based on a SWOT (strengths, weaknesses, opportunities and threats) analyses, we argue that public health workers have the potential to play an important role in disseminating health promotion programs and advocating for broader statewide policies that could reduce tobacco use and exposure to environmental tobacco smoke. However, such an opportunity is missed with neither designated funding nor a nationally-dedicated office to tobacco control in Hungary. PMID- 20586228 TI - Evaluation of breastfeeding in a Baby-Friendly City, Corum, Turkey. AB - Corum is one of the Baby-Friendly Cities in Turkey since 2004. For optimum initiation and continuing of breastfeeding, not only educating the mothers about breast milk and breastfeeding is enough but also social support systems including family support is very important. The aim of this study was to evaluate the breast feeding status and the effect of lactation counseling support (LCS) on breastfeeding and social support in a Baby-Friendly City. In a cross-sectional study, a questionnaire was administered to 800 mothers of infants between 2-24 months admitted to government and private hospitals and government health facilities in urban part, towns and villages of Corum for any reason, between February 2006 and February 2007. Mothers' and fathers' age and education level, the type of family, the sex and the order of children, the type of birth, the infants' birth weights, planned pregnancy did not affect the participation of LCS. Mothers who gave colostrum as the first food had more frequently taken LCS than mothers who gave prelacteal foods (p < 0.01). The percentage of LCS in mothers who knew the expression of breast milk and didn't give bottle feeding was higher compared to others (respectively; p < 0.01, p = 0.05). Mothers supported from husbands, sisters and mothers-in-law participated more frequently (p < 0.05) in LCS than unsupported mothers. LCS is very important for mothers to develop correct attitudes and behavior about breastfeeding and family collaboration. Further regional studies should be done to follow the changes in breastfeeding status, to detect the local problems and to arrange special training programmes. PMID- 20586229 TI - Effect of working posture on occurrence of musculoskeletal disorders among the sand core making workers of West Bengal. AB - The sand core making process is performed manually in West Bengal involving a large number of workers of lowest economic strata. The core making workers most often work for a prolonged period of time and they are forced to handle various amounts of heavy load during the entire period of work. In this study an attempt was made to identify the work related musculoskeletal disorders among the sand core-making workers. Fifty male workers engaged in carbon dioxide and chemical core making work at an unorganized sector at Baruipur, Calcutta were randomly selected for this study. A detailed modified Nordic questionnaire study on discomfort feeling was performed among the core making workers. REBA method was applied to analyze the working posture. Finally, discomfort level and risk level of the individual working postures were calculated by the use of risk level and discomfort level scale. From the questionnaire study it was revealed that most of the core making workers grind often in awkward postures. The workers were affected by musculoskeletal disorders like pain at low back (100%), hand (40%), shoulder (30%), wrist (20%) and neck (20%). It has been also found that there is a significant (p < 0.05) correlation between discomfort level and risk level of the individual working postures of the workers. It was concluded from the study that health of the core-making workers was highly affected by different awkward postures and that they suffer from posture-related musculoskeletal disorders primarily affecting the low back region. PMID- 20586230 TI - Determinants of regional differences in sick leave duration for homogeneous groups in The Netherlands: their implications for social security policy-making. AB - OBJECTIVES: Regional differences in sick leave duration determinants were studied between in age and profession homogeneous groups in different regions in The Netherlands, i.e. Utrecht and Southern Limburg, in order to find any effects of socio-cultural factors. MATERIAL AND METHODS: 137 participants in Utrecht and Southern Limburg were interviewed. Data of sick leave duration were obtained from the social fund. RESULTS: A statistical comparison of sick leave duration figures showed that, in Southern Limburg, determinants of 'health status' (questions about perceived health and burnout due to work) and 'individual characteristics and circumstances' (age, gender and satisfaction with private circumstances) were associated with sick leave duration and, in Utrecht, the 'work contents' determinant autonomy. CONCLUSIONS: In the regions studied, different determinants appeared to be associated with sick leave duration and for some of them the European integration was assumed to have a lasting effect. Nationwide policy interventions to reduce sick leave duration should take into account the existence of regional differences in determinants predicting sick leave duration and the potential effects of different socio-cultural characteristics on laying claim to social security. PMID- 20586231 TI - Symposium held in Prague November 11, 2009, as a tribute to Professor Karel Raska, the outstanding epidemiologist. PMID- 20586232 TI - An active participant in the eradication program of smallpox. PMID- 20586233 TI - Karel Raska--the development of modern epidemiology. The role of the IEA. PMID- 20586234 TI - Fate and behaviour of copper and zinc in secondary biological wastewater treatment processes: I. Evaluation of biomass adsorption capacity. AB - The current sources of copper and zinc in municipal wastewaters have been considered, and the changes in the concentrations and quantities of these two elements entering sewage treatment works over the last three decades have been calculated. The concentrations and quantities of the heavy metals cadmium, chromium, copper, mercury, nickel, lead and zinc, entering UK sewage treatment works, have been reduced by between 50% and 90% during this period. However, the reductions in copper and zinc appear to be at the lower end of these ranges and thus remain a cause for concern, particularly their concentrations in sewage effluents and their potential environmental impacts on receiving waters. Bench studies have been undertaken to predict removals by three types of biological wastewater treatment plants: trickling filters, conventional activated sludge and membrane bioreactors, to determine if any of these processes are more efficacious for the removal of these metals. These results suggest that, despite membrane bioreactor biomass achieving the lowest effluent suspended solids concentration and having the lowest effluent chemical oxygen demand, which is accepted as a surrogate measure of organic chemical chelating ability of the aqueous phase, they produce the highest effluent values for the two metals in this study (copper and zinc). Removals of zinc and copper in biological wastewater treatment processes are probably primarily determined by those factors influencing metal solubility in the biomass matrix. PMID- 20586235 TI - Fate and behaviour of copper and zinc in secondary biological wastewater treatment processes: II. Removal at varying sludge age. AB - The mechanisms for the removal of heavy metals during secondary biological treatment of wastewater, with particular emphasis on the activated sludge process, are considered. It is concluded that the predominant mechanism is the entrapment and co-settlement of insoluble metal species in the mixed liquor (biomass). Secondary extracellular polymeric materials, particularly extracellular polysaccharides and other capsule-forming materials, may also play a role. In general, removal of both copper and zinc was superior at the higher sludge ages employed in this study, 4.3 and 8 days, and can in part be attributed to the superior removals of both biochemical oxygen demand and effluent suspended solids achieved at these sludge ages compared with the lowest sludge age studied, 3.6 days. For both copper and zinc there is an increase in soluble metal across the activated sludge process. However, significant removal of both metals occurs as a consequence of the removal of substantial amounts of insoluble metal. The presence of returned sludge liquors, high in settleable solids, to the mixed liquor appears to moderately enhance the percentage removal of copper and zinc. Membranes used in place of secondary sedimentation also enhance removal of both metals by reducing effluent suspended solids. It is concluded that there is potential for maximizing metal removal by optimization of secondary biological treatment in a sustainable manner, without recourse to energy-intensive or chemically-dependent tertiary treatment technologies. PMID- 20586236 TI - Removal of Cd(II) from aqueous solution by a composite hydrogel based on attapulgite. AB - Chitosan-g-poly(acrylic acid)/attapulgite composite with 30 wt% attapulgite content was used to remove Cd(II) from aqueous solutions. The parameters influencing the adsorption were investigated. When Cd(CH3COO)2 was used as the solute of the solution, the equilibrium adsorption capacity was evidently larger than that of the other three cadmium salts (Cd(NO3)2, CdCl2, CdSO4). Results from kinetic experiments showed that the rate of Cd(II) adsorption on the composite was quite fast, more than 90% of Cd(II) adsorption occurred within the initial 3 min, and the adsorption equilibrium may be reached within 10 min. The adsorption process can be well described by the pseudo-second-order kinetic model. The equilibrium adsorption isotherm was fitted for not only the Langmuir model but also the Freundlich model. Fourier transform infrared spectra before and after adsorption of Cd(II) on the composite showed that complexation was considered as the main mechanism. To evaluate the reuse value of the composite, a consecutive adsorption-desorption process was performed five times, and the results implied that the composite has the potential for regeneration and reuse. PMID- 20586237 TI - Reusable nanomaterial and plant biomass composites for the removal of Methylene Blue from water. AB - A novel composite has been prepared from nanomaterials and powdered orange peel. The composite is adhered to a plastic strip and may be employed for the removal of synthetic dyes from aqueous solutions, for example from dyehouse effluents. Using Methylene Blue (CI Basic Blue 9) as the reference dye, the characteristics of the adsorbent have been studied. The effect of pH, type of nanomaterial (e.g. carbon nanotubes, activated carbon nanotubes, or titanium dioxide nanoparticles), contact time, and reusability have each been investigated. The results show that the adsorption capacity of suspended orange peel powder, an orange peel strip, and an activated carbon nanotube/orange peel strip were 46%, 67% and 78%, respectively. The uptake of dye was greatly affected by the pH of the solution, maximum absorption being obtained at pH 10, and none at all at pH 2. The improved performance was probably the result of the increased area available for adsorption compared with orange peel powder alone. The system was found to be reusable for up to six cycles without appreciable loss of adsorption and desorption efficiency. The nanomaterial in the composite enhanced performance, not only by increasing adsorption efficiency but also by inhibiting biodegradation of the orange peel powder, thereby increasing the life of the strips. The system offers an economical, user-friendly, efficient and reusable adsorption treatment for the removal of dyes from wastewater. PMID- 20586238 TI - Olive mill wastewater treatment in a membrane bioreactor: process stability and fouling aspects. AB - An external ceramic membrane bioreactor was used to carry out an experimental study of process stability and fouling aspects for olive mill wastewater (OMW) treatment. Three diluted OMW solutions were used to continuously feed the reactor. An acclimated biomass was employed and the process stability was followed on the basis of the permeate quality and some operating parameters (pressure, temperature, mass flow and dissolved oxygen). Several backpulse combinations were tested to determine the best filtration and backwash time. It appeared that a short backpulse duration was sufficient and that the behaviour, in terms of the permeate flux versus time, stabilized. In terms of increased permeate flux, the effect of the backpulsing depended on the nature of the solution. This improvement was limited, but, in the long-term, backpulsing makes it possible to maintain a constant permeate flux over a period of several days. PMID- 20586239 TI - Degradation of Active Brilliant Red X-3B by a microwave discharge electrodeless lamp in the presence of activated carbon. AB - Degradation of Active Brilliant Red X-3B (X-3B) in aqueous solution by a microwave discharge electrodeless lamp (MDEL) in the presence of activated carbon was investigated. The preliminary results proved this method could effectively degrade X-3B in aqueous solution. The removal percentages of colour and chemical oxygen demand were up to approximately 99% and 66%, respectively, at the conditions of 0.8 g/L dye concentration, 20 g/L activated carbon, pH 7.0 and 8 min microwave irradiation time. The degradation basically belonged to first-order reaction kinetics and its rate constant was 0.42 min(-1). No aromatic organics were detected in the final treated solution, indicating that the mineralization was relatively complete. By studying the change in solution properties, it could be concluded that MDEL-assisted oxidation was the dominant reaction mechanism. In addition, the influence of operational parameters and reuse of activated carbon were also discussed. PMID- 20586240 TI - Polymers as bubble surface modifiers in the flotation of algae. AB - Previous research has shown that dosing polymers directly to the saturator of a dissolved air flotation (DAF) process in replacement of upstream coagulation can achieve algae removal comparable to that of conventional treatment, as a result of bubble modification. In this paper we further explore the application of polyDADMAC as a bubble modifier in this adapted DAF process. It was determined that removal improved with increasing polyDADMAC molecular weight (MW). Removal efficiencies obtained for Microcystis aeruginosa were much greater than those predicted theoretically, and were attributed to a potential projection of the polymer into the aqueous phase, increasing the swept volume of the bubble. PolyDADMAC dose and the resultant removal efficiency were dependent on the character of the associated algogenic organic matter (AOM). The AOM with high MW, low charge and significant hydrophobicity and protein content enabled co operative binding, while that of high charge and low hydrophobicity hindered attachment. PMID- 20586241 TI - Application of Fe(VI) in the treatment of Zn(II)-NTA complexes in aqueous solutions. AB - The higher oxidation state of iron, i.e. Fe(VI), was exploited to treat the synthetic wastewater containing Zn(II)-NTA. The decomposition of Zn(II)-NTA by Fe(VI) was investigated with the help of analytical data obtained for the change in Fe(VI) concentration, dissolved organic carbon (DOC) and total soluble Zn(II) concentration as a function of time at various concentrations of Zn(II)-NTA and at constant Fe(VI) concentration. The UV-Visible data was used to explain the reaction kinetics for redox reactions between Fe(VI) and Zn(II)-NTA. The pseudo first-order rate constant was calculated keeping the Zn(II)-NTA concentration in excess and hence the overall second-order-rate constant was obtained. Fe(VI) reduction was almost unaffected with the 1000 times increase in ionic strength (NaNO3), as well as in the presence of completely oxidized background electrolytes. However, Fe(VI) reduction was greatly affected in the presence of both SO3(2-) and NO2(-) especially at higher concentrations, indicating a competitive reduction took place between Zn(II)-NTA and Na2SO3 or NaNO2 in the Fe(VI) treatment. These results were again supported by the dissolved organic carbon observations since relatively very low removal of the dissolved organic carbon occurred in the presence of Na2SO3 and NaNO2. PMID- 20586242 TI - Denitrification in presence of acetate and glucose for bioremediation of nitrate contaminated groundwater. AB - With the current increasing interest in aquifer denitrification, recent attention has been given to cost-effective in-situ treatments such as Enhanced In-Situ Biological Denitrification (EISBD), which intends to stimulate the indigenous bacterial activity by injecting an external organic substrate and/or nutrients to the aquifer matrix. Within this context, laboratory batch assays have been conducted to develop a strategy for in-situ denitrification of a nitrate contaminated aquifer in Argentona, Catalonia (Spain). The assays were run under aerobic and anaerobic conditions at a temperature of 17 degrees C to better simulate the conditions of the aquifer. Acetate and glucose were added to assess their potential to promote heterotrophic denitrifying bacteria activity. Overall, the results revealed that indigenous micro-organisms had the potential of reducing nitrate under appropriate conditions. Nitrate removal was complete and faster under anaerobic conditions, though high nitrate removals were also attained under initial aerobic conditions when a readily organic compound was amended at a sufficient dosage. The results also revealed that a significant amount of the available organic carbon was consumed by processes other than denitrification, namely aerobic oxidation and other microbial oxidation processes. To sum up, the results of this study demonstrated that addition of organic compounds into the groundwater is a promising method for in-situ bioremediation of nitrate in the Argentona aquifer. This approach could potentially be applied to a number of situations in which nitrate concentration is elevated and where indigenous micro-organisms with potential to reduce nitrate are present within the aquifer material. PMID- 20586243 TI - Adsorption of basic dyes in single and mixture systems on granular inorganic organic pillared clays. AB - The adsorption of two basic dyes, CI Basic Yellow 28 and CI Basic Green 4, was studied in single and binary solute systems using two classes of inorganic organic pillared clay granules as sorbents (300-400 microm and 700-800 microm). These were prepared by high-shear wet granulation from an Al cetyltrimethylammonium bromide intercalated clay powder (particle diameter < 50 microm). Adsorption rate data indicate that BY 28 adsorbs more rapidly than BG 4 and a pseudo-first-order model was found to fit the kinetic curves, with regression coefficients above 0.98. Adsorption isotherms in single solute systems at pH 3 and pH6 were respectively analysed according to the Langmuir and Freundlich models using non-linear regression. Best fits were obtained with the Langmuir model. In binary dye systems the adsorption at three molar ratios (1:9, 1:1 and 9:1) demonstrated that the adsorption of BG 4 was greater than that of BY 28 on all the sorbents studied; this was in agreement with the results obtained for single solute systems. Increasing the granule size decreased dye adsorption, an effect in accordance with the Sheindorf-Rebuhn-Sheintuch model. PMID- 20586244 TI - [Evolution conceptions about the nature of aging]. AB - The work presents aging as the age-dependant fractal process consisting in increasing of quantity of homeostasis disturbances at molecular, subcellular, cell-tissue and system levels. The facts testifying to simultaneous evolutional complication of aging and anti-aging forms are considered. The evolutional stages of the beginnings of "molecular", "segregational", "conditional", "clonal", postmitotic and systemic aging types are displayed. PMID- 20586245 TI - [An outline on the phylogenetic history of metazoa aging phenomenon (to the study of creating a common metazoa aging theory)]. AB - The evolution of aging phenomenon in Metazoa was from the very beginning developing from potentially immortal forms to those more prone to aging. Potential immortality is an ancestral feature gradually lost in the course of evolution; at the same time aging and death resulting from aging are not obligatory but highly desirable property of existence of Metazoa with gamogenesis; this is a prerequisite of evolutionary progress as it facilitates species formation processes accelerating phylogenetic groups radiation and thus gives certain outlying evolutionary advantages, namely, accelerating the evolutionary process and the speed of substitution of one species by others. The main principle of aging phenomenon evolution is as follows: it's the substitution of internal factors of death of nonaging Metazoa with external ones programmed in genome. Aging mechanisms add up to limitation of repairing and regeneration capabilities of adult phenotype and/or by extermination of the whole pool of stem cells or its part only. Aging is a holistic process and it can't be drawn down to one of the known cellular processes which in their turn can't be the initial trigger of this process that is programmed in the genome in a vague form (there is no aging program as it is): if at some stage of ontogenesis the reparation mechanism disablement is genetically programmed then this is really the aging phenomenon programming. Mainly full or partial postmitotic design of an organism is programmed, and it is in its turn a factor securing the "harmfulness" of cellular mechanisms, decreasing the physiological potential of an organism with age. By this it increases the chances of mortality among Metazoa species. On the whole the presented material points to the fact that to develop a common aging theory of Metazoa we don't have to substantially replenish the database of biological science, but we need a new understanding of known facts, which determine the initial cognitive position. PMID- 20586246 TI - [The demographic and professional risks of depopulation of the Russian labor forces (analytical review)]. AB - The comparative analysis of the aging process of population in the context of demographic transition was represented in this article. The values of the basic medico-demographic indices of aging population for Russia and developed countries were identified. The results of the United Nations forecasts, probabilistic prognosis of quantity and age-gender structure for the Russian population were analyzed. The state of demographic trouble in Russia was convincingly shown. Special attention was given to the examination of the demographic and professional risks of a reduction in the population at the working ages, to an increase in the demographic load on the labor forces. The need for further studies was proven, dedicated to the use of geroprotectors and contemporary gerontotechnologies as means and methods of the prevention of premature work ability reduction, retarding of the aging processes of the worker's organism, decrease in the level of mortality and increase in the professional longevity. PMID- 20586247 TI - [State of individual health: a forecast of effectiveness of the organism activity]. AB - This article presents the forecast of a state of a human health basing on system approach, a system of indices, suggests a method of evaluation of the forecast of effectiveness of an organism work, offers the basic ratios for calculations, and gives an example. PMID- 20586248 TI - [Stress-immunity-health (problem of premature aging in veterans of special risk subdivisions)]. AB - The posttraumatic stress with neurotic and somatic manifestation and the precocious aging was shown in the veterans of special risk subdivisions. The early atherosclerotic involvement of heart vessels, brain, legs etc. was revealed. A significant role in the precocious aging and atherosclerosis of vessels play immune changes: the combination of immunodepressive and autoaggressive states revealed in the veterans. PMID- 20586249 TI - [Vitauct of superorganism biosystems (by the example of communities of social insects and biocenoses)]. AB - Unidirectional irreversible changes occur continuously in complex biosystems consisting of large number of different elements. First, they increase the stability of the systems but then decrease it bringing for the probability of their disappearance from the Earth. By the example of communities of social insects and biocenoses the reactions of superorganismic level prolonging their life are considered. PMID- 20586250 TI - [Age-related features of intracellular calcium homeostasis in rat cardiomyocites in postinfarction heart remodeling]. AB - Research results of features of an intracellular calcium homeostasis in 4 and 12 month's rat cardiomyocites at postinfarction cardiosclerosis are presented. It is shown that the myocardium of animals in the old rats group is more susceptible to extrasystolic impacts. In the pathology conditions additional extrasystolic influences also had the expressed age specificity of inotropic response. The data testifying to almost identical dynamics of postextrasystolic cycles of intact myocardium in animals of investigated age groups has been obtained. The different postextrasystolic potentiation in the remodeled myocardium in old and young rats testified to different of sarcoplasmic reticulum ability to accumulate additional calcium ions. The conclusion was made that the myocardium of animals in the old rats group has more chance for development of hemodynamic significant disturbance of cardiac rhythm as a consequence of age-related changes processes of the electromechanical coupling in cardiomyocites. PMID- 20586251 TI - [Reaction of the testicles of old animals on administration of human fetal tissues]. AB - The aim of the work was to study the effect of fetal tissues on histological structure of testicles of the old mice. The data obtained suggest that the implantation of human fetal tissues postponed age degeneration of tissues. PMID- 20586252 TI - [Peptidergic regulation of the expression of signal factors of fibroblast differentiation in the human prostate gland in cell aging]. AB - The effect of short peptides T-32, T-38 and cardiogen on the expression of signaling factors of the differentiation of human prostate's fibroblasts (PFM), which are the main cells of its microenvironment--protein CXCL12, WEDC1 and ghrelin in aging cultures has been studied. Confocal laser microscopy has demonstrated that all the investigated peptides possess the ability to actively enhance the expression of the above markers, whose synthesis significantly reduced in senescent cultures. It has been shown that the rate of expression of the studied factors in older cultures (after 7 passages) under the action of the peptides have a tendency to even higher than those of controls (young culture, after 1 passage). Thus, peptide T-38 is the most active among the investigated ones. These studies show promise for detailed development of methods of peptides' regulation of aging and age-correction of violations of functioning of the prostate gland. PMID- 20586253 TI - [Cell renovation in the intestinal epithelium in aging]. AB - The ability to cell renovation of two basic cell types of intestinal mucosa is the important mechanism for the regulation and support of the gut physiological functions in aging and under the influence of the ecological negative factors. The study of the processes of cell renovation of the intestinal epithelial and neuroendocrine cells in physiological and radiological aging has a great interest, because the irradiation in the subletal doses could be considered as the model of artificial aging, and this fact enables studying of the radiological influence as the ecological factor, promoting the aging. In this study, the increase of cell proliferation in intestinal mucosa in physiological as well as artificial aging was observed. It was shown, that the total population of mitotic cells increases two times. These data testify about active participation of the mechanisms of cell renovation in the safety of gut functions during aging. PMID- 20586254 TI - [Slowing down the rate of irreversible age-related atrophy of the thymus gland by atopic autotransplantation of its tissue, subjected to long-term cryoconservation]. AB - An experimental procedure has been developed enabling to slow down the rate of irreversible atrophy of the thymus gland. The atopic autotransplantation of its tissue subjected to prolonged cryoconservation enables one to inhibit the aging of the organism with respect to several biochemical and immunological indicators. PMID- 20586255 TI - [Effect of additional administration of ferric ion on the life span of irradiated animals]. AB - There were established regularity of early biological reactions, restoration and life span shortening in rats after gamma-irradiation of animals with low (25 and 50 cGy) or 600 cGy doses in combination with various regimen of ferric ions introduction with drinking water (60-63 mg/l). PMID- 20586256 TI - [Radiation-protective action of bioantioxidant complex of ginseng extract in the model of the radiation-induced aging during development of radiation-induced neoplasms]. AB - The study of the geriatric properties of the bioantioxidant complex "Neovitin" received from a biomass of ginseng, against formation of radio gene tumors was continued. The preparation was applied to the laboratory animals exposed to chronic gamma irradiation by low doses, by all period of irradiation and thirty days in the post beam period. The expressed anticancerogenic effect of "Neovitin", reducing formation of radio gene tumors, including malignant, as well as reduction of a spectrum of new growths were proved. PMID- 20586257 TI - [Change of blood volume in the kidney cortical and medulla vessels in aging process]. AB - We studied the volumes of arterial and venous vessels (cortical and medulla) of a kidney, excepting microcirculation system. The research covered 76 corrosion preparations of kidneys of people, aged from 21 till 85 years, died from diseases which could not affect on morfofunctional condition of kidneys and their vascular system. We have found out that morphological changes in kidneys at aging are characterised, basically, by progressing nephrosclerosis. The major factor provoking development of sclerous changes in a kidney is the age changes of kidney arterial vessels. It is proved that structural changes in venous and arterial vessels in involution are characterised by gradual decrease of volume of cortical substances vessels, where the considerable part of blood proceeds. PMID- 20586258 TI - [Effect of one-time injection of calcitonin preparations on glucose and calcium level in rats of different age groups]. AB - The effect of domestic preparations of calcitonin (the bull one--thyrocalcitonin and the pig one--calcitrin) on the blood glucose and calcium level in rats was studied. Calcitrin made more effective action on the investigating measures. Calcitrin evoked marked hyperglycemic effect in rats of all age groups (immature, adult, old). More significant rise of blood glucose was detected in immature and old animals. Maximum increase of blood glucose after calcitrin injection in immature rats is 53 +/- 7%, in adult--19 +/- 2%, in old--47 +/- 3% to initial glucose concentration. More marked hypocalcaemia was in immature rats in comparison with adult rats. There are functional (immature), close (adult) and marked (old) negative correlation was established between glucose and calcium level. PMID- 20586259 TI - [The effect of 2,4-dinitrophenol on the intensity of oxidative processes in the rat liver during prolonged experiment]. AB - The effect of uncoupler 2,4-dinitrophenol on the oxidative processes intensity in liver biomembranes of different age and sex of rats during longitudinal experiment was studied. It was established that 2,4-dinitrophenol in the used concentration hadn't essential negative effect on the organism of females and their posterity. On the young, 3-3,5-month old males it was shown that long-term xenobiotic administration had been accompanied by intensification of the rate of oxygen consumption, decrease of the rate of reactive oxygen species formation in microsomal redox-chain, decline in lipid hydroperoxides and protein carbonils levels in blood serum and liver microsomes, and also by increase of their mean lifespan. The obtained results may testify the possibility of correction of oxidative processes intensity in tissues of mammals and their lifespan by means of modulation of membrane electron transport chains activity. PMID- 20586260 TI - [Predictive value of variability of the laboratory indices in the development of premature aging]. AB - Diagnostics of those or other pathological processes is connected with an estimation of deviations of corresponding laboratory indexes from their reference values. Results of the research enable to use the indexes of individual variability of laboratory tests as a criterion of individual resistance, which has a prognosis value in studying of age pathology. It also essentially expands ideas about activation of the peroxide oxidation of the lipids as the basic trigger factor of the accelerated aging. PMID- 20586261 TI - [Quality of life and biological age of elderly persons with alcohol dependence in conditions of European North]. AB - The data of the assessment of quality of life of persons at the involutional age suffering from alcohol dependence in comparison with features of their physiological age have been presented. Quicker aging among the persons with alcohol dependence traced in parallel with their low social functioning and quality of life have been detected; it has been shown that in the elderly women, alcoholization accelerates aging in greater degree. PMID- 20586262 TI - [Iron metabolism in elderly patients with ulcer disease]. AB - We examined 72 elderly patients with ulcer disease at the age from 55 till 79 years. We studied an iron metabolism (haemoglobin, serum iron, serum ferritin) and its correlation with a clinical current of ulcer disease. It is established that the anemic syndrome is the frequent companion of ulcer disease in elderly and old patients. Deficiency of iron negatively influences on dynamic abdominal painful and dyspepsia syndromes, considerably aggravates clinical display of a cardiovascular pathology. PMID- 20586263 TI - [Prevalence of different types of urinary incontinence and concomitant diseases in elderly patients]. AB - This article presents the data on the prevalence of different types of urinary incontinence and concomitant diseases on the basis of answers to questions obtained from 398 patients over 65 years. We have analyzed the relationship among certain diseases in patients with urgent and stress incontinence. Lower urinary tract symptoms were more common in men over the age of 70 years; no such a tendency in women was observed. Among the patients older than 70 years, the probability of urgency and urgent incontinence increases significantly, regardless of gender. In older women the urgent and mixed urinary incontinence associates with the concomitant diseases. Stress urinary incontinence in women was not associated with any of the indicators of general health and social activity. PMID- 20586264 TI - [The influence of the length of work on the adaptation of the circulatory system of male teachers of different specialities]. AB - The problem of human adaptation to the social and biological conditions of the existence is placed at the center of attention of many natural and social sciences studying vital activity of a person in all forms it displays. The basis of the existence of the human population is considered to be a social and labor activity of people. Recently, the importance of researches has increased, which enables to evaluate the functional state of a person under the circumstances of adaptation to a particular occupation. These researches are the theoretical foundation to develop methods for improving the efficiency of people in many kinds of professions, and especially it is important for elderly people. The results of social and hygienic researches among the middle-aged and elderly people involved in different trades vary and are stipulated generally by the conditions of the working environment, difficulties and intensity of work processes. The study of the features of the circulatory system of a person in the process of working activities is a significant issue in physiology. It is found that the greatest changes in the functional parameters of the blood circulation are observed in young and elderly people. In the same way, it is shown that it depends on the type of adaptation, age characteristics, work experience which result in slowing down the rate of the processes of the nervous system, the regulation of blood circulation becomes inert, the level of physical health reduces, and age displacements accelerate. These changes are considered as a result of increased spending of physiological reserves of the organism in various environmental conditions. PMID- 20586265 TI - [Clinical and pathogenetic characteristics of the craniocerebral trauma received by elderly patients after stroke]. AB - In 174 patients of elderly and senile age features of a clinical picture and pathogenesis of a craniocerebral trauma of a different severity occurred in different terms after the previous stroke and in different circumstances have been studied. The mutual relations of traumatic and vascular processes are complex, the vascular pathogenetic features of a trauma influence actively to the brain, earlier damaged by an ischemic stroke, increasing the probability of the heavy form of a combined cerebral pathology and the unfavourable forecast. However the vascular encephalopathy in these conditions "does not develop" in posttraumatic one and chronic vascular-brain frustration absolutely prevail in all cases above traumatic ones. This fact is to be taken into consideration to further treatment and rehabilitation. PMID- 20586266 TI - [Results of dental implantation in elderly patients]. AB - In absence of contraindications, with competent planning and complex oral mouth treatment and adequate use of surgical and orthopedic protocols, the dental implantation could be successfully implemented for esthetical and functional rehabilitation of elderly patients with different forms of adentia. Dental implantation can significantly increase the quality of life of elderly patients. PMID- 20586267 TI - [Peculiarities of pathogenesis, clinical picture and new approaches to the treatment of symptomatic epilepsy in the elderly and geriatric patients]. AB - The purpose of this work was to find out single pathogenetic mechanisms of epilepsy development in elderly patients with chronic brain blood-circulation deficiency. There were results of 49 patients' clinical study aged 64-86, suffering from epilepsy with the disease onset after 60. The correlation between the degree of atherosclerotic lesions of brain vessels and epileptic activity presented in EEG is given in the paper. The clinical example of successful treatment of hemodynamic-valuable stenosis of carotic artery in patients with symptomatic post-stoke epilepsy is supplied. The question of drug ethiopathogenic treatment and anti-convulsant application in elderly patients is discussed. PMID- 20586268 TI - [Quality control criteria for hospital care of aged patients with otorhinolaryngologic pathology]. AB - This article presents data about criteria of quality of hospital aid for aged patients with otorhinolaryngologic pathology worked out by the authors basing on analyses of 708 cases. The criteria of effectiveness, adequacy and satisfaction of aged patients are described. PMID- 20586269 TI - [Metalloprotease-mediated HB-EGF release regulates EGF receptor transactivation in A431 cells under oxidative stress]. AB - We have shown earlier that H2O2 induces EGF receptor transactivation in different cells overexpressing EGF receptor. Mechanism of H2O2-induced EGF receptor transactivation in A431 human epidermoid carcinoma cells was examined in this work. We have demonstrated autophosphorylation of Tyr1045, 1068, 1148, 1173 as well as phosphorylation of Tyr845 of EGF receptor in response to H2O2, as assessed by autophosphorylation specific antibody. Tyrosine phosphorylation of EGF receptor by H2O2 did not involve receptor autophosphorylation at Tyr992. Blocking functions of metalloproteases by broad-spectrum inhibitor GM6001 suppressed H2O2-induced phosphorylation of EGF receptor, suggesting dependence of the transactivation on metalloproteases activity. To elucidate the possible role of EGF receptor agonists in its activation we used HB-EGF and TGF-alpha neutralizing antibody. H2O2-induced EGF receptor phosphorylation was inhibited by HB-EGF, but not TGF-alpha, neutralizing antibody. Taken together, our data suggest that, in human epidermoid carcinoma A431 cells, H2O2 stimulates EGF receptor transactivation via metalloprotease-dependent HB-EGF release and autophosphorylation. PMID- 20586270 TI - [Immunological similarity of diphtheria toxin and EGF receptor]. AB - Cardiomyopathy and neuropathy are the two commonly observed complications in diphtheria patients and in, some instances, individuals vaccinated against diphtheria. The nature of these complications remains not well understood. It was suggested that autoimmunity may play a role in the development of these afflictions. Based on functional similarities between diphtheria toxin (DT) and epidermal growth factor receptor (EGFR), which both can bind to the heparin binding EGF-like growth factor (HB-EGF) precursors, we suggested that antibodies developed against DT can cross react with EGFR. Here, using serum from healthy donors (n = 10) and diphtheria patients (n = 15), we demonstrated that B-subunit of DT has the antigenic epitopes similar to those of EGFR. Diphtheria toxin as well as EGFR could be recognized by antibodies raised against EGFR and by serum antibodies from diphtheria patients. Moreover serum of diphtheria patients competitively inhibits binding of anti-EGFR antibodies to the receptor. The truncated diphtheria toxin without B-subunit could be detected by serum antibodies of diphtheria patients, but not by anti-EGFR antibodies. Collectively, these studies demonstrate cross-reactivity of antibodies raised against B-subunit of DT and extracellular domain of EGFR and suggest that clinically observed post diphtheria complications may result from autoimmune inhibition of EGFR function and possible destruction of receptor-positive tissues. PMID- 20586271 TI - [Non-viral gene therapy approach for regenerative recovery of skin wounds in mammals]. AB - The rate and character of skin tissue regeneration after wounds, burns and other traumas depend on the cell proliferation within damaged area. Acceleration of healing by stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches to wound treatment consisting in the transfer of genes encoding mitogenic growth factors to wound area. The most important step in the development of gene therapy approaches is the design of gene delivery tools. In spite of high efficacy of viral vectors, the non-viral means have some preferences (low toxicity, low immunogenity, safety and the absence of backside effects). Among non-viral gene delivery tools, molecular conjugates are the most popular because of their efficacy, simplicity, and the capacity to the targeted gene transfer. In the present work we have developed two molecular conjugates- NLS-TSF7 and NLS-TSF12 consisting of the modified signal of nuclear localization of T-antigen of SV40 virus (cationic part) and the peptide ligands of mammalian transferrin receptor (ligand part). These conjugates bind to plasmid DNA with formation of polyelectrolytic complexes and are capable to deliver plasmid DNA into cells expressing transferrin receptors by receptor-mediated endocytosis. Transfer of the expression vector of luciferase gene in the complex with molecular conjugate NLS-TSF7 to murine surface tissues led to about 100 fold increasing of luciferase activity in comparison with the transfer of free expression vector. Treatment of slash wounds in mice with the complexes of expression vector of synthetic human gene encoding insulin-like growth factor 1 with molecular conjugates NLS-TSF7 led to acceleration of healing in comparison with mice treated with free expression vector. The results obtained confirm the high efficiency of the developed regenerative gene therapy approach for the treatment of damaged skin tissues in mammals. PMID- 20586272 TI - [CD14++CD16- and CD14+CD16+ human monocytes adhesion to endothelial cells]. AB - Two subsets of monocytes were identified in humans and other mammals blood based on different levels of CD14 and CD16 expression. These subsets have different patterns of adhesion molecules and chemokine receptors, which suggest different modes of interaction with endothelium and tissue traffic. Here, we investigated the ability of CD14+CD16+ and CD14++CD16- monocytes to adhesion to endothelial cells monolayer in presence and in the absence of pro- and anti-inflammatory cytokines. We demonstrated that CD14+CD16+ monocytes had higher level of adhesion to intact endothelial cells monolayer than CD14++CD16- monocytes. Significant increase in adhesion of CD14++CD16- and CD14+CD16+ monocytes subpopulations was observed in the presence of both TNF alpha and TNF alpha combinations with other cytokines. IFN gamma and IL-4 showed no independent effects on adhesion of monocytes. These results have demonstrated that both CD14++CD16- and CD14+CD16+ monocytes can be recruited to inflamed endothelium, but, in the absence of inflammation, CD14+CD16+ monocytes adhere to endothelial cells two times stronger than CD14++CD16- monocytes. PMID- 20586273 TI - [Correlations of sister chromatids cohesion complexes distribution with histones H3 and H4 modifications]. AB - The formulation of "histone code" theory brings active investigations of the role of histone modifications and other supramolecular factors of DNA condensation in transcription regulation. In this work, we have analyzed the localization of methylated histones on 9, 36 and 79 lysines, hyperacetylated H4 histone, and subunits of cohesion complex DRAD21 relatively of Drosophila melanogaster polytene chromosomes chromatin condensation. We propose the hypotheses of a cascade regulation of transcription activity defined by histone modifications and the adaptive role of sister chromatids cohesion in the transcription of high active and extensive genes. PMID- 20586274 TI - [The effect of inhibitors of serinethreonine protein kinases on Arabidopsis thaliana root morphology and microtubules organization in its cells]. AB - The effect of different types of serine/thereonine protein kinases inhibitors (cyclin-dependent, Ca2+-calmodulin-dependent and protein kinase C) on microtubules organization in cells of Arabidopsis thaliana main primary root zones were investigated in vivo. The microtubules in epidermal and cortex cells in the transition and elongation zones as well as microtubules in trichoblasts and atrichoblasts in the differentiation zone showed the greatest sensitivity to protein kinases inhibitors studied. It was established that microtubules in these cell types modified their initial transverse/oblique orientation to a chaotic or longitudinal relative to the major axis of primary root as a result of serinethereonine protein kinases inhibition. The microtubules in cells in root meristematic zone as well as in root hairs were less sensitive to influence of protein kinases inhibitors tested. Alterations of microtubules orientation in the cells in primary root zones under the influence of serinethereonine protein kinases inhibitors led to further disturbances in growth and differentiation processes. It was assumed that phosphorylation of microtubules proteins, especially tubulin, might be involved in the regulation of these processes. PMID- 20586275 TI - [Structure of neuromuscular junctions and differentiation of striated muscle fibers of mdx mice after bone marrow stem cells therapy]. AB - Mdx mice are a model of Duchenne muscular dystrophy caused by deficiency of dystrophin. Muscles of mdx mice are characterized by high levels of striated muscle fibers death and, accordingly, by a high level of its regeneration. Moreover, the structure of neuromuscular junctions in mdx mice is altered. Changes in the structure of mdx mice neuromuscular junctions against a background of increasing differentiation of striated muscle fibers after C57BL/6 Lin (-) bone marrow stem cells transplantation were investigated. The muscles were studied in 4, 8, 16 and 24 weeks after transplantation. We observed that the level of striated muscle fibers loss was decreased from the 4th week after transplantation of bone marrow stem cells. Accumulation of muscle fibers without centrally located nuclei began from the 8th week, and dystrophin synthesis was increased at the 16th and 24th weeks after bone marrow stem cells transplantation. Longitudinal sections of quadriceps muscles of mdx mice showed decrease in the number of acetylcholine receptors clusters in neuromuscular junctions and a simultaneous increase in acetylcholine receptor clusters area during the 4th week after transplantation. In 16 weeks after bone marrow stem cells transplantation, total neuromuscular junction area was increased due to increase in the area of acetylcholine receptors clusters and to increase in their number as well. Thus, single intramuscular transplantation of C57BL/6 Lin (-) bone marrow stem cells induces an increase in differentiation of mdx mice striated muscle fibers and improves the structure of neuromuscular junctions. PMID- 20586276 TI - [Doxorubicin and menadione reduce cell proliferation of Saccharomyces cerevisiae by different mechanisms]. AB - The aim of this study was to determine the impacts of doxorubicin and menadion on cell proliferation, cell distribution in accordance with the phases of the cell cycle phase, glutathione concentration, ribonucleotide reductase expression, and Yap1 dependent redox-sensitive pathway activity using Saccharomyces cerevisiae as eukaryote cell model. Our data show that menadione induced cell cycle arrest in G1-phase, reduction of intracellular GSH, an increase in GSSG concentration, and dose-dependent increases in ribonucleotide reductase expression and the activity of Yap1 pathway. Doxorubicin induced cell cycle arrest in G1- and S-phases, increased GSH and GSSG concentrations, increased expression of ribonucleotide reductase, and modulated Yap-dependent pathway activity. PMID- 20586277 TI - [Nuclear matrix organization of the chromocenters in cultured murine fibroblasts]. AB - In the current work, the structural organization of nuclear matrix of pericentromeric heterochromatin blocks (chromocenters) inside cultured murine fibroblasts was investigated. After 2 M NaCl extraction without DNase I treatment, chromocenters were extremely swelled, and it was impossible to detect them using conventional electron microscopy. Using immunogolding with anti topoisomerase IIalpha antibody, we demonstrated that residual chromocenters were subdivided into numerous discrete aggregates. After 2 M NaCl extraction with DNase I treatment, the residual chromocenters appeared as a dense meshwork of thin fibers, and using this feature, the residual chromocenters were easily distinguished from the rest of nuclear matrix. After extraction with dextran sulfate and heparin, the chromocenters were decondensed, and chromatin complexes having rosette organization (central core from which numerous DNA fibers radiated) were seen. Probably, the appearance of these rosettes was a consequence of incomplete chromatin extraction. Thus, the nuclear matrix of pericentromeric chromosome regions in cultured murine fibroblasts differs morphologically from the rest of nuclear matrix. PMID- 20586278 TI - [Chromosomal instability of in vitro cultured mouse embryonic stem cells and induced pluripotent stem cells]. AB - A perspective of using embryonic stem (ES) and induced pluripotent stem (iPS) cells in clinical medicine makes karyological analysis of these cells an important issue. Using methods of classical and molecular cytogenetics chromosomal analysis, we have carried out karyological study of two mouse ES and two iPS cell lines derived de novo. We have found monosomy of X chromosome in all studied ES and iPS cell lines, thus making a modal number of chromosomes in these cell lines 39. A chromosomal instability (aneuploidy) was revealed in both studied iPS cell lines. Moreover, we have detected chromosomal rearrangements and chromosomal fragments in one of iPS cell line. Our findings underline the importance of careful cytogenetic evaluation of pluripotent cell lines, especially iPS cell lines, which should be carried out prior to any clinical use of these cells. PMID- 20586279 TI - [Salicylate-induced modification of plant proteomes (review)]. AB - Here we present a brief review of the reports concerning proteome modifications under the influence of salicylic acid, which is one of the major mediators of both local and systemic immunity. We describe also the results of our own studies of the salicylate-induced changes in proteomes of pea leaves and roots. Fifteen salicylate-inducible proteins, which were previously unknown, have been identified. Unlike the roots, leaves accumulated some chloroplast proteins and enzymes capable of degrading the pathogen cell walls. In the roots, salicylic acid increased the content of enzymes, improving the resistance of plant cells themselves, and promoted the disappearance of reductase of oxophytodienic acid. The latter could lead to inhibition of jasmonic acid synthesis and stimulation of local immunity. High (apoptotic) concentration of salicylic acid intensified synthesis of root proteins involved in the formation of heteroprotein complexes, which play an important role in the functioning of the signaling system, DNA synthesis and repair, and protein synthesis, refolding, and proteolysis. PMID- 20586280 TI - [Immunochemical methods of mycotoxin analysis (review)]. AB - The review is devoted to comparative characterization of immunochemical methods of detection of mycotoxin, which belongs to one of the priority groups of the food contaminants. It has been shown that the high specificity and the possibility of mycotoxin detection in low concentrations combined with existent diverse equipment allow for considering the immunochemical methods of analysis to be the most promising for wide practical application. The analytical characteristics of the existent developments are presented; the merits and demerits of the different kinds of immunoanalytical systems are compared. PMID- 20586282 TI - [Variability of light-induced circular dichroism spectra of photosystem I complexes of cyanobacteria]. AB - Circular dichroism (CD) spectra of photosystem I (PSI) complexes of the cyanobacteria Thermosynechococcus elongatus, Arthrospira platensis and Synechocystis sp. PCC 6803 were studied. CD spectra of dark-adapted PSI trimers and monomers, measured at 77 K, show common bands at 669-670(+), 673(+), 680(-), 683-685(-), 696-697(-), 702(-) and 711(-) nm. The intensities of these bands are species specific. In addition, bands at 683-685(-) and 673(+) nm differ in intensity for trimeric and monomeric PSI complexes. CD difference spectra (P700(+)-P700) of PSI complexes at 283 K exhibit conservative bands at 701(-) and 691(+) nm due to changes in resonance interaction of chlorophylls in the reaction center upon oxidation of P700. Additional bands are observed at 671(-), 678(+), 685(-), 693(-) nm and in the region 720-725 nm those intensities correlate with intensities of analogous bands of antenna chlorophylls in dark-adapted CD spectra. It is suggested that the variability of CD difference spectra of PSI complexes is determined by changes in resonance interaction of reaction center chlorophylls with closely located antenna chlorophylls. PMID- 20586281 TI - [Sulfated polysaccharides and their anticoagulant activity (review)]. AB - Published data on the sulfated polysaccharides of various origins that display an anticoagulant activity are summarized and analyzed. The methods used for producing semisynthetic derivatives are considered. A key role of the polysaccharide structure in the mechanisms of specific interaction with various blood plasma proteinases is discussed. The effects of the content and location of sulfate groups in polysaccharides and their molecular weight on the degree of the studied activity are assessed. PMID- 20586283 TI - [The model of resting forms of mycobacteria for testing of drugs for latent forms of tuberculosis]. AB - The new model of obtaining of ovoid resting forms Mycobacterium smegmatis, which are morphologically different from vegetative (rod-like) cells, was developed. Ovoid forms were characterized by a drastically decreased level of metabolic activity, an increased stability to heat processing and antibiotics action, and also by prolonged (more than 2 months) storage time preserving colony-forming ability. Obtained resting forms of mycobacteria may be used in test-systems for checking efficiency of new medical agents against latent forms of tuberculosis and determination of role of these of those genes in entering rest state. PMID- 20586284 TI - [Biosynthesis of poly-3-hydroxybutyrate-3-hydroxyvalerate copolymer by Azotobacter chroococcum strain 7B]. AB - The ability of Azotobacter chroococcum strain 7B, producer of polyhydroxybutyrate (PHB), to synthesize its copolymer poly-3-hydroxybutyrate-3-hydroxyvalerate (PHB HV) was studied. It was demonstrated, for the first time, that A. chroococcum strain 7B was able to synthesize PHB-HV with various molar rates of HV in the polymer chain when cultivated on medium with sucrose and carboxylic acids as precursors of HV elements in the PHB chain, namely, valeric (13.1-21.6 mol %), propanoic (3.1 mol %), and hexanoic (2.1 mol %) acids. Qualitative and functional differences between PHB and PHB-HV were demonstrated by example of the release kinetic of methyl red from films made of synthesized polymers. Maximal HV incorporation into the polymer chain (28.8 mol %) was recorded when the nutrient medium was supplemented with 0.1% peptone on the background of 20 mM valerate. These results suggest that that the studied strain can be regarded as a potential producer of not only PHB but also PHB-HV. PMID- 20586285 TI - [Formation of glycated recombinant leghemoglobin in Escherichia coli cells]. AB - A nonenzymatic glycation of the recombinant leghemoglobin expressed in Escherichia coli cells was demonstrated for the first time. This process involved the heme pocket and gave low-spin leghemoglobin species. A correlation between the degree of E. coli protein glycation and synthesis of poly-beta-hydroxybutyric acid was found, suggesting that the accumulation of reserve carbon sources and nonenzymatic glycation could be alternative processes. PMID- 20586286 TI - [Spectrophometric analysis of volatile compounds in microorganisms]. AB - A simple modification of a spectrophometric method was proposed for the rapid detection of microorganisms based on their ability either to excrete or to absorb volatile compounds. The method provides the possibility of contactless control for bacterial growth at a concentration above 10(7) cells/ml. In addition, the method allows discriminating mutants of the fungus Neurospora crassa defective in the nitrogen metabolism from the wild type strains. It is likely that nitrite reductase and nitrate reductase enzymes regulated by the nit-2 and nit-6 genes are involved in formation of the water soluble volatile compounds of this organism. PMID- 20586287 TI - [The study of adaptation mechanisms of Yarrowia lipolytica yeast to alkaline conditions by means of proteomics]. AB - Using proteomic technologies--two-dimensional electrophoresis in denaturing conditions in combination with mass spectroscopy of MALDI-TOF proteins--we demonstrated, for the first time, that the most noticeable alteration of protein composition of a Yarrowia lipolytica cell during adaptation to alkaline conditions was an increase of mitochondrial proteins relatively to proteins of cytoplasm. PMID- 20586288 TI - [A heterologous production of the Trametes hirsuta laccase in the fungus Penicillium canescens]. AB - A heterologous protein expression in the fungus Penicillium canescens is described for the first time. The fungal strains producing Trametes hirsuta laccase under control of a highly efficient promoter of the P. canescens gene bgaS has been constructed. These strains efficiently transcribe the T. hirsuta 072 laccase gene with a correct intron splicing. Activity of the secreted heterologous laccase in the culture liquid reaches 3 U/ml, accounting for 98% of the total laccase activity, which demonstrates a high efficiency ofheterologous secretion. The synthesized P. canescens laccase has the same molecular weight as the enzyme produced by T. hirsuta 072. PMID- 20586289 TI - [Comparative analysis of respiratory activity in the wild type strain of Neurospora crassa and its photoreceptor complex mutants]. AB - Cell respiratory activity of protoplasts obtained from the wild type of Neurospora crassa and photoreceptor complex WCC--white collar 1 (wc-1) and white collar 2 (wc-2)--mutants of Neurospora crassa strains was investigated. Respiration inhibition by KCN in the presence of 25 mM succinate was similar in all strains and did not exceed 83-85% against control. The significant induction of KCN-resistant respiratory pathway occurred under 1% glucose oxidation in wc-1 and wc-2 mutants if compared with the wild type strains. The inhibitors of the main (cytochrome) pathway of electron transfer in mitochondria-1 mM KCN and antimycin A (4 microg/ml)--blocked the respiration rate of the protoplasts from N. crassa wild type by 75%, while the cell respiration of wc-1 and wc-2 strains was suppressed by approximately 50%. The specific inhibitor of alternative oxidase--10 mM salicylhydroxamic acid (SHAM)-in combination with the blockers of mitochondrial electron transfer chain caused the total suppression of respiratory activity of protoplasts in all studied strains. It is supposed that an increase of KCN-resistance in WCC mutants under glucose oxidation is connected with alternative oxidase activation as the result of failure in reception and signal transduction of active oxygen species. PMID- 20586290 TI - [The influence of cultural medium composition on the proteolytic enzyme secretion of fungus Rhizoctonia solani]. AB - It was shown that change of medium growth composition of photopathogenic fungus Rhizoctonia solani Kuhn, especially accessible sources of nutrition, leads to change of both quantity of produced proteinases and their action specificity. The mineral source of nitrogen suppressed the fungus proteinase secretion on cultivation medium containing potato thermostable proteins but an organic source of nitrogen accelerated mycelium growth and increased proteinase secretion. On the basis of an analysis of a fungus extracellular proteinase substrate specificity, it is established that the presence of thermostable proteins of a potato in the cultural liquid induces the secretion of trypsin-like proteinases mainly, and the addition of yeast extract to this growth medium induces the secretion of subtilisin-like ones, thus suppressing the trypsin-like enzymes production. This fact can indicate that mycelium of fungus R. solani loses pathogenic properties and becomes saprophytes when the growth medium was enriched by an organic source of nitrogen. PMID- 20586291 TI - [The influence of light, hormonal, and carbohydrate signal systems on ELIP genes expression in gun-mutants Arabidopsis thaliana]. AB - It is proven that retrograde tetrapyrrole-induced plastid signals, light signals, and signals induced by hormones and carbohydrates influence expression of nuclear genes of plastid stress proteins ELIP in Arabidopsis thaliana L. Plastid signals differently regulated expression of genes from multigene family of photosynthesis proteins (ELIP and Lhcb2) and were modulated by light. The influence of a regulator of plant growth--abscisic acid--led to activation of expression of ELIP genes in the light. Carbohydrates suppressed transcription of ELIP genes. Thus, signals of exogenous (light) and endogenous (retrograde signals, hormones, carbohydrates) origin influence the expression of ELIP genes. These types of signals probably interact with each other and favor the increase of resistance of plants to the action of stress factors of the environment. PMID- 20586292 TI - [Photobiochemistry of folates: a photochemical reduction of folic acid]. AB - Exposure of deaerated folic acid solutions containing an electron donor to UV radiation (310-390 nm, I = 0.4 W m(-2)) induced formation of dihydrofolic acid (DHFA), a photoexcitation which gave tetrahydrofolic acid (THFA). Only DHFA was formed in the presence of EDTA (E'o = +0.40 V), while the presence of stronger reductants-NADH (E'o = -0.32 V) and boron hydride (E'o = -0.48 V)-induced photoreduction to THFA. It was demonstrated that UV radiation had no effect on the THFA formylation, giving the coenzyme 5,10-methenyltetrahydrofolic acid and its transformation into another coenzyme, 5-formyltetrahydrofolic acid. PMID- 20586294 TI - [Changes in the plastid apparatus of apical meristem cells of potato tubers upon growth regulation with jasmonic acid]. AB - A comparative ultramorphometric study of the effect of jasmonic acid (JA) on the plastid apparatus in apical cells of potato tubers varying in physiological state was performed. When tubers were treated with JA at forced rest, the plastid apparatus of apical cells decreased in area and plastid proliferation was suppressed. When treatment was performed during growth, the area of the plastid apparatus remained unchanged, division was suppressed, and plastid budding was stimulated in apical cells. There was also a common response to JA that was independent of the physiological state of tubers. JA stimulated the development of the internal membrane system in plastids, reduced the amount of protein inclusions, and increased the portion of plastids having cisterns of the granular endoplasmic reticulum (GER) around their envelopes. The ultrastructural changes in plastids made it possible to assume that JA increases the biosynthetic activity of the plastid apparatus in apical meristem cells of potato tubers. PMID- 20586293 TI - [Immunomodulating activity of chitosan derivatives with salicylic acid and its fragments]. AB - A study of biological activity of the derivatives of the chitin-chitosan oligomer with salicylic acid and its fragments showed that chitosan salicylate actively protected potato tubers against Phytophthora infestans but sharply inhibited reparation of potato tissues. N-(2-Hydroxybenzyl)chitosan exhibited good protective properties but did not influence wound reparation. N-(2-Hydroxy-3 methoxybenzyl)-N-pyridox-chitosan, which contained the pyridoxal and 2-hydroxy-3 methoxy fragments, was the most efficient, stimulating both defense against late blight and wound reparation in potato tissues. PMID- 20586295 TI - [Melafen effect on ATP-dependent accumulation of calcium in plasma membrane vesicles from cells of potato tubers]. AB - Synthetic growth regulator melafen (10(-5)-10(-10) M) was tested for an effect on the Ca2+ accumulation in plasma membrane vesicles (PMVs) isolated from potato Solanum tuberosum L. tubers at forced rest and sprouting. Melafen proved to regulate the Ca2+ accumulation in PMVs by changing the activity of Ca2+, Mg(2+) ATPase of the plasma membrane, while no effect was observed with respect to Ca2+ outflow from vesicles. The melafen effect on Ca2+, Mg(2+)-ATPase activity depended on the physiological condition of tubers and the melafen concentration. PMID- 20586296 TI - [Influence of the cycle number in processing of cellulose from waste paper on its ability to hydrolysis by cellulases]. AB - Hydrolytic ability of laboratory enzyme preparations from fungus of the Penicillium genus was investigated using kraft pulp from nonbleached softwood and bleached hardwood cellulose as substrates. The enzyme preparations were shown to efficiently hydrolyze both softwood and hardwood cellulose. The yields of glucose and reducing sugars were 24-36 g/l and 27-37 g/l from 100 g/l of dry substrate in 48 h, respectively, and depended on the number of substrate grinding cycles. PMID- 20586297 TI - [On-board medical support system (MSS) of flights of promising aerospace sets (design)]. AB - It was suggested as the main compositive fractions MSS to consider the base system of automated evaluation of blood redistribution (BR) in body means of crew members protection and prophylaxis (CMPP) of unfavourable effects of flight factors to organism and also the automated circuit of CMPP' control. The advanced MSS includes 4 original measuring channels for registration of the base physiologic indices (electrocardiogram, venous-arterial pulsegram of neck vessels, reogram of head, earlap vessels pulsegram) the dynamic of which allows to determine with the help of computer the BR-integral parameter. The CMPP automated control circuit unites the separate protecting means in common system and executes the individual selection of regimes and CM PP-composition in accord with, first of all, body reactions manifestation and, secondly, individual physiologic status of spaceman. As CMPP was selected the negative pressure production around lower body part. Approlation of constructed active laboratory engineering mock-up MSS has performed investigations with participation of 29 subjects (Volunteers) under the modeling of hemodynamic shifts, developing in human body in short-term antiorthostatic hypokinesia (-10 degrees), as well as, in combined effect of antiorthostatic hypokinesia (-10 degrees), Coriolis acceleration and optokinetic stimulation. Results of investigations have showed, that the use of advanced MSS gives the indices of operator professional activity on the average of 17-32% under the decrease of hemodynamic stressful. PMID- 20586298 TI - [Some approaches to the countermeasure system for a mars exploration mission]. AB - In article discussed physiological and methodical principles of the organization of training process and his (its) computerization during Martian flight in conditions of autonomous activity of the crew, providing interaction with onboard medical means, self-maintained by crew of the their health, performance of preventive measures, diagnostic studies and, in case of necessity, carrying out of treatment. In super long autonomous flights essentially become complicated the control of ground experts over of crew members conditions, that testifies to necessity of a computerization of control process by a state of health of crew, including carrying out of preventive actions. The situation becomes complicated impossibility of reception and transfer aboard the necessary information in real time and emergency returning of crew to the Earth. In these conditions realization of problems of physical preventive maintenance should be solved by means of the onboard automated expert system, providing management by trainings of each crew members, directed on optimization of their psychophysical condition. PMID- 20586299 TI - [Indicators of innate and adaptive immunity of cosmonauts after long-term space flight to international space station]. AB - Results of innate and adaptive immunity indicators research at 12 cosmonauts who took part in long (128-215 days) expeditions to the International space station (ISS) are presented. It is shown that a space flight can lead to deflection of deviations in human immune system. These shifts occurred in decrease of phagocytes, NK, T-lymphocytes functional activity and also in abilities of immunocompetent cells to synthesize cytokines. Significant individual changes are noted in reaction of immune system to the long term space flight conditions specifying on individual predisposition to development of immune reactance infringements in the conditions of varying gravitational influences. PMID- 20586300 TI - Reliability of utricular function testing sinusoidal translation profile during unilateral centrifugation. AB - The unilateral centrifugation test is one of the few vestibular tests that evaluate the utricles side by side. During this test, a subject is rotated about an earth vertical axis at high rotation speeds (e.g. 400 degrees/s) and translated sideways along the interaural axis to align the axis of rotation consecutively with the right and the left utricle. The combined rotation and translation induces ocular counter rolling (OCR), which is measured using three dimensional video-oculography. Recently, a new model has been proposed to analyse the OCR. The model is based on contributions from both the semicircular canals and the utricles. Concomitant with the new model a new stimulation profile using a sinusoidal translation profile during the unilateral centrifugation has been introduced [1]. The current study presents the test-retest reliability as well as the robustness of the new stimulation method, based on data of 67 healthy subjects. Test-retest reliability was based on repeated measurements of a group of subjects. To test the robustness of the new sinusoidal translation paradigm, we investigated the effect of a different amplitude of the sinusoidal translation (6 cm instead of 4 cm) and of an offset in translation (from -3 to +5 cm, instead of from -4 to +4 cm) on the parameters. Several statistical measures were used to reflect the reliability: intraclass correlation coefficient (ICC), the "coefficient of variation of the method error" and the "minimal difference" (MD). All relevant variables from the physiological model for the OCR induced by unilateral centrifugation show a good to excellent reliability during the test retest study and the relevant parameters remain unaffected by the changes applied to the translation profile (p > 0.05) as predicted by the model. Additionally, all observed differences are smaller than the MD values calculated in the test retest part of the study. PMID- 20586301 TI - [Comparative analysis of cosmonauts skeleton changes after space flights on orbital station Mir and international space station and possibilities of prognosis for interplanetary missions]. AB - A summary of investigations results of human bone tissue changes in space flight on the orbital station (OS) Mir and international space station (ISS) using dual energy X-ray absorptiometry (DXA) is given. Results comparative analysis revealed an absence of significant differences in bone mass (BM) changes on the both OS. Theoretically expected BM loss was observed in bone trabecular structure of skeleton low part after space flight lasting 5-7 month. The BM losses are qualified in some cases as quicly developed but reversible osteopenia and generally interpreted as evidence of bone functional adaptation to the alterating mechanical loading. It was demonstrated the high individual variability BM loss amplitudes. Simultaneously was observed the individual pattern of BM loss distribution across different segments of skeleton after repetitive flights independently upon type of OS. In according with the above mentioned individual peculiarities it was impossible to establish the dependence of BM changes upon duration of space missions. Therefore we have not sufficiently data for calculation of probability to achive the critical demineralization level by the augmentation the space mission duration till 1.5-2 years. It is more less possibility of the bone quality changes prognosis, which in the aggregate with BM losses determines the bone fracture risk. It become clearly that DXA technology is unsuffitiently for this purpose. It is considered the main direction which may optimized the elaboration of the interplanetary project meaning the perfectly safe of skeleton mechanical function. PMID- 20586302 TI - [Auditory motion aftereffects with approaching and withdrawing sound sources]. AB - Auditory motion aftereffects with approaching and withdrawing sound sources were investigated in the free field. Radial sound moving image (approaching or withdrawing) was imitated by means of rhythmical noise impulse sequences with arising or diminishing amplitude presented through two loudspeakers placed at 1.1 and 4.5 m from the listener. The adaptation to the auditory approaching and withdrawing exposure caused changing of evaluation by listeners the test signals followed by adapting ones. Stationary test signals were perceived by listeners as moving to the direction opposite to ones presented during adaptation. Stimuli subtly moving to the adapting signals' direction were determined as stationary. The peculiarities of auditory motion aftereffects with approaching and withdrawing sound sources were similar to ones with horizontally moving sound sources. PMID- 20586303 TI - [Mechanisms of forming and working reproductive dominant]. AB - Spectral and coherent analyses of biolectrical brain activity in gestational dynamics and in early post-natal period has been made at 560 pregnant women and at 35 women during menstrual cycle. The encephalography (EEG) examination of 184 women participating in the program in vitro fertilization (IVF) has been carried out. According to the theory and the experiments, it can be concluded that the occurance of one-foetus pregnancy is accompanied by the forming ofgestational dominant-constellation of nervous centres. Its central chains are located in limbico- diencephal and neocortical structures. Neocortical representation is formed within frontal and central areas of the hemisphere, that is contralatteral to the placenta replacement. Some electrographical phenomena have been found out and they is experimently prove this ideas. It is supposed, that one of the ways of increasing of efficacy of the IVF methods is the investigation of the mechanisms of central-peripheral integration in women's reproductive system. PMID- 20586304 TI - [The importance of biological and social factors in school success]. AB - Three groups of children with learning difficulties (a total of 62 children) are dealt with in this study according to their cognitive and psychological special features. In the first group the difficulties are a symptom of the FMR1-gene dysfunction. In the second group the poor school performance is associated with social interaction problems and high intelligence level. In the third group of gifted children with low verbal intelligence parameters the poor school performance occurred because of unevenly developed verbal and non-verbal abili ties. We demonstrate the importance of complex neurophysiological, neuropsychological and clinical psychological investigation for establishing the reasons for school difficulties. PMID- 20586305 TI - [Short-term adaptation of cardiovascular system of children of 5-7 years to mental loading]. AB - For the purpose of revealing of adaptable possibilities of cardiovascular system research of 150 children of 5-7 years by a method oftetrapolar reography on Kubichek at rest and at mental loading. Research has shown that from 5 to 7 years there are essential changes of parameters of central haemodynamics: increase systolic and diastolic arterial pressure (SAP and DAP), increase stroke volume (SV) and the minute blood volume (MBV), and as decrease heart rate (HR). Mental loading causes two variants of reaction of stroke volume. The first variant was characterized by increase SV, the second - decreaseb SVand increase DAP. Short term Adaptation to mental loading at the majority of children of 5-7 years independently of and orientation of changes SVwas not accompanied by pressure of regulation's mechanisms of cardiovascular system and had favorable character. At 13-15% of all surveyed children short-term adaptation to mental loading was characterized by considerable pressure of regulation's mechanisms of cardiovascular system. It was expressed in increase the SAP, DAP, HR, GPVR, SPVR, decrease SVand MBV, and also the long period of reconstraction the majority of parameters of central haemodynamics. PMID- 20586306 TI - [Functional characteristics of cardiovascular system in adolescents with prehypertension]. AB - Based on the results of sanogenetic monitoring the health of schoolchildren found that among high school students to the proportion of adolescents with elevated blood pressure (hypertension + hypernormotension) increases from 15-20% in 8th class to 30-50% in 9-11th classes, while the proportion of adolescents with hypertension was 3.7% in all age groups. Comparison of blood pressure with parameters of neurovegetative regulation of the cardiovascular system revealed that the presence of high normal blood pressure in 13-14-year-olds and 17-18-year olds correlated with an increase in the proportion of low frequencies in the spectrum of HRV and lower values of the sensitivity of arterial baroreflex. At the age of 15-16 years, high-normal blood pressure accompanied by a decrease in heart rate, increase the sensitivity of arterial baroreflex and correlates with reduced power high-frequency part of the spectrum of HRV. When performing a functional test (an increase of "dead" breathing space) in hypernormotension teenagers 15-16 years, unlike normotensive peers, there is a reduction of finger blood pressure, and relative power of low frequencies in the spectrum of HRV, which may be associated with maladaptive functional changes in the sympathetic unit of autonomic regulation. PMID- 20586307 TI - [On the conjugate hand reaction. Note IV. Changing rates of conjugate hand reaction to the sound and light signals modality for surgical interventions in the subcortical brain structures in humans]. AB - The results of the study on conjugate reaction time (BP) of hands (time of simple reaction) in 16 patients--with Parkinson's disease, cerebral palsy and spastic torticollis before and after surgery--are stated. The analysis of conjugate BP left arm and arm BP signals of sound and light modality with a warning signal to determine the morphological structures which depend on the friendly reaction was performed. Was found that part of the surveyed patients had no violations of conjugate BP, the other part had significant changes in the magnitude of the correlation coefficient, by which evaluated conjugate BP left and right hands. Violations of the correlation coefficient between BP left arm and right arm BP were observed or sound, or doth on the sound, and the light signal. Violations of the conjugate hand reaction were observed in the ventro-lateral talamotomii, subtalamotomii and pallidotomii. PMID- 20586308 TI - [The extent of temperature sense and pain appreciation recovery in the dermatomes of cauda equine roots after lumbar intervertebral dischernia elimination]. AB - Temperature sense and pain appreciation has been studied in the dermatomes of cauda equine roots in patients with lumbar intervertebral disc hernia before treatment, in the immediate and long-term periods of observation after disc hernia elimination. Temperature sense and pain appreciation has been determined to be disordered not only in the dermatome of compressed root, but in the dermatomes located proximally and distally as well. The manifestation of negative changes was observed to a greater extent during temperature sense examination. After disc hernia elimination the recovery of temperature sense and pain appreciation in the dermatomes of cauda equine roots is rather limited, especially in the area of compressed root innervations. The positive shifts of temperature sense and pain appreciation values in different zones of examination in the immediate periods of observation after surgery were noted, on the average, in 55% of cases, those in the long-term periods of observation--in 36% patients only. The improvement of pain appreciation (heat pain) was noted to a greater extent both in the immediate and long-term periods of observation. PMID- 20586309 TI - [Final blood lactate concentration after incremental test and aerobic performance]. AB - The aim of the study was to check the hypothesis that elite endurance athletes (junior and national team) show the decreased final blood lactate concentration after incremental test till exhaustion with increased aerobic performance level. 20 physical active men and 45 elite middle and long distance endurance athletes (speed skaters, triathletes, cross country skiers) participated in the study. Significant negative correlations (r = -0.59--0.87) were found between final blood lactate concentration after incremental test till exhaustion and aerobic performance (anaerobic threshold (AT)) for athletes groups and not for physically active subjects. Moreover the less final blood lactate concentration and more VO2 at AT have elite speed skates, the higher volume of type I muscle fibers in working muscle they have (r = -0.84 and r = 0.7, accordingly). PMID- 20586310 TI - [Serum glucose level in acute severe hypoxia in human at rest]. AB - Study of the effects of acute normobaric hypoxia was performed on a group of young healthy males (age 19-23, n = 10). Conditions of acute normobaric hypoxia were modeled by using oxygen-nitrogen mixture containing 8% of oxygen as a breath gas. That level of oxygen corresponds with its partial pressure at 7000 meters above sea level. A number of different analyses were conducted during experiment: levels of glucose, pyruvate, lactate in peripheral venous blood, hemoglobin, pH, hematocrit, partial pressures of 02 and CO2, hemoglobin saturation. It was shown that on 5th minute of hypoxia serum glucose level decreased significantly (p < 0.05). The average decrease was about 0.76 mmol/l in its maximum and lowest individual glucose levels were 4.0 mmol/l or higher. Serum glucose level returned to background values (assessed before the test) at 10th minute of experiment. In our opinion results of the study suggest that syncopal form of height hypoxia may be caused by the reasons other than hypoglycemia. PMID- 20586311 TI - [Chronotype of human in the north]. AB - Long term acting climatic and social factors of the North causes desynchronization of human circadian system that can lead to increase in risk of age-associated diseases. Earlier on small sample we have shown, that the higher latitude of residing in the North, the higher rate of occurrence of late chronotype. It is noted also, that parameters of daily rhythm at late chronotype person are less expressed, than at early one. The purpose of present research is to study distribution of rates of various chronotypes depending on latitude of residing. Chronotypes were assessed by the Munich Chronotype Questionnaire (MCTQ). Our study includes 772 inhabitants of Komi Republic. It was shown that there is a significant shift to prevalence of late chronotype among inhabitants of the North. Thus, increase in rate of persons with late chronotype, circadian system of which is most sensitive to negative action climatic and social factors of the North, can be one of the causes of its desynchronization and increasing in risk of age-associated diseases at northerners. PMID- 20586312 TI - [Dynamic characteristics of the external respiratory function in young men of the north in the annual cycle]. AB - The annual cycle in young men (19.0 +/- 0.9 years), inhabitants of the European North (62 degrees) were studied: peak (PVR) and the instantaneous volumetric rate at the time of expiration 25, 50, 75% of forced vital capacity (FVC), average volume rate during exhalation from 25 to 75% FVC, respiration rate, time to attain the PRV and FVC. Indicators of lung function were determined on microprocessor spirograph SPM-01-R-D. Revealed that young men in the annual cycle significantly (F-test) changed only the speed characteristics of respiratory function, time function had no significant differences. Also is revealed a more variation in the annual cycle of values of speed parameters of lung function compared with those for the inhabitants of middle latitudes, indicating that the adaptive responses of lung function and certain restriction ofbronchial permeability on the level of medium and especially small bronchi. The peak and the instantaneous volumetric rate at the time of expiration 25, 50 and 75% FVC and the average volumetric expiratory flow rate in the range of 25 to 75% of forced vital capacity of lungs from male northerners in the cold season more, in warm weather--less. PMID- 20586313 TI - [Leucocytes conservation in the near-zero temperature]. AB - The intensive metabolism and fast exhaustion of an energy potential of nuclear blood cells at positive temperatures essentially reduce terms of their storage in a viable condition. However for the clinical purposes given thensfusion environment is the extremely necessary. The popular method of preservation of cells at ultralow temperature (-196 degrees C) is limited in application since assumes use of the liquid nitrogen, the special equipment, trained engineering personnel. The work is devoted to development effective and simple in execution of a method of preservation of leukocytes in conditions of temperatures about zero (+2 degrees--0 degrees C) with use of a household elecrorefrigerator and new cryopreservation a solution. PMID- 20586314 TI - [Computer method for fusional reserves evaluation with objective control of fusion break]. AB - A method of assessing fusional reserves using an interactive computer program, which allows to monitor the subjects report on the moment of fusion break with artificial increase of convergence or divergence of the vii sual axes in the measurement process was developed and tested. Control is achieved through the use of a purely binocular stimuli--random-dot stereograms, as well as dynamic markers, which are added to the main test object in a random order in the course of the measurement procedure to change the type of test-object. Test-object with a marker, encoded in the stereogram, is seen only at the expense of binocular mechanisms, and in violation ofifusion is no longer visible. Its disappearance helps the subject to determine when failure of fu-sion occurred, and the type of object with a marker before this point allows the experimenter to check the subject. Statistical analysis of primary and repeated measurements of fusion reserves in 72 subjects confimed the sufficient reliability of the method. PMID- 20586315 TI - [EEG changes in comparison of rest states with open and closed eyes in complete darkness]. AB - There are visible changes in EEG in transition from an awake resting state with eyes closed (REC) to an awake resting state with eyes opened (REO). These changes are usually treated as reflexion of brain activity reorganization in reply to visual perception. In present investigation we examined EEG records in awake resting states with opened and closed eyes in complete darkness. 30 healthy volunteers participated in this investigation. EEG (1.5-50 Hz) were recorded according to standard methods from 19 zones. EEG spectral power and coherence analysis demonstrates that REC and REO states differ even if the comparison corresponds to a situation of complete darkness. The differences are significant in any of the frequency ranges delta, theta, alpha1, alpha2, beta1, beta2, gamma. As compared states REC and REO don't differ neither by external visual information nor by illumination level therefore we presumably consider observed EEG changes as correlated with involuntary shift of anticipatory attention from interoceptive state with eyes closed to exteroceptive state with eyes opened. PMID- 20586316 TI - [Dependence of anticipatory grip force in catching task on previous trial]. AB - Heavy or light object fell into the cup that sitting subject held between thumb and index fingers. A grip force applied to the cup was measured at the moment of impact. The grip force was stronger in trials following the trial with heavy object than after the trial with light object independently of object weight in the current trial. It means that the anticipatory grip force was planned accounting the result of previous trial. PMID- 20586317 TI - [Mechanism of photosensitized luminescence of singlet oxygen dimols in air saturated pigment solutions]. AB - Luminescence of singlet oxygen dimols (1O2)2 with the main spectral maximum at 703-706 nm and much weaker bands at 640 and 770-780 nm was studied using mechanical phosphoroscopes in aerobic solutions of the nonfluorescent photosensitizer phenalenone in CCl4 and C6F6 at relatively low radiant power. The spectrum of this luminescence resembles that of dimol luminescence, which we had detected previously in solutions of porphyrins and other compounds. It was shown that, in phenalenone solutions, the mechanism of dimol luminescence involves reaction of two 1O2 molecules and one ground-state pigment molecule. It is most likely that light is emitted by the dimol-pigment contact complexes formed as a result of collisions of 1O2 with metastable, probably triplet intermediates that result from reactions of 1O2 with pigment molecules. It is proposed that this luminescence mechanism is of general importance for many organic and biologically important systems where singlet oxygen is generated. However, a comparison with the literature data suggests that the luminescence of this type can be detected at relatively low rates of 1O2 generation. At high singlet oxygen generation rates, dimol luminescence with the main maximum at 635-637 nm dominates, which is likely caused by direct collisions of 1O2 molecules. PMID- 20586318 TI - [Effect of nitroderivatives of fullerene C60 on amyloid fibrils of Abeta(1-42) peptide of the brain and muscle X-protein]. AB - The antiamyloidogenic capacity of water-soluble nitroderivatives of fullerene C60: methyl ester of LN-[(2-nitroglyceryl) fullerenyl] proline, methyl ester of LN-[(2,3-dinitroglyceryl) fullerenyl] proline, and 2 nitroxyethyl ether LN-([2 (nitroxy) ethyl] fullerenyl) proline has been studied in vitro by high-resolution electron microscopy. It was shown that these fullerene C60 nitroderivatives are able to prevent the formation of amyloid fibrils by the brain Abeta(1-42)-peptide and muscle X-protein and to destroy mature fibrils. Electron microscopy is a promising method for selecting effective antiamyloidogenic drugs. The antiamyloidogenic activity of nanodimensional fullerene C60 nitroderivatives offers strong possibilities for creating a new nanotechnology for the therapy of amyloidoses. PMID- 20586319 TI - [A precise equilibrium equation for four steps of binding between TBP and TATA box allows for the prediction of phenotypical expression upon mutation]. AB - Among the main events of transcription initiation of TATA-containing genes in eukayotes are the recognition and binding of the TATA-box by the TATA-binding protein (TBP) to start the preinitiation complex formation on the nucleosomal DNA. Using the equilibrium equation for step-by-step TBP/TATA-binding, we have analyzed 69 experimental datasets on the characteristics of biologicacally important features altered by TATA-box mutations. Among these features, the TBP/TATA-complex parameters, the transcription level, the activity of gene products, yeast colony growth at a dose of growth inhibitor (phenotype), and the heterogenity of the response of a population to unspecific environmental stress have been described. Significant correlations were found between in silico prediction for TBP/TATA affinity and experimental data for in vivo and in vitro test-systems based on 15 cell types of 19 species, RNA polymerases II and III, and natural, recombinant or mutant TBP. Such an invariant impact of the step-by step TBP/TATA-binding on the biological activity of complex systems, from a molecule to a population, might be due to the fact that TBP/TATA-complex formation precedes specific steps of transcription machinery assembly, which provide the multivariant jigsaw puzzle according to the expression pattern of each eukaryotic gene. PMID- 20586320 TI - [Application of molecular dynamics simulation to the interpretation of atomic force microscopy data]. AB - A new approach to the interpretation and refining of experimental atomic force microscopy (AFM) data has been developed, which is based on the comparison with the simulated static imaging mode operations output. We have applied the approach to atomic force microscopy studies of lisozyme. During this test, we have obtained distinct precise AFM images of lysozyme monomers adsorbed from a clear aqueous solution onto a mica wafer. The images were compared with the corresponding images obtained by molecular dynamics simulations. We performed two steps of simulations to reproduce the environment and processes of the AFM study of lysozyme. The first step was intended to obtain the adsorbed structure of lysozyme; it was performed using the NAMD molecular dynamics software. At this step, the simulated environment of lysozyme was a water box, and the mica wafer was manually modeled according to its crystal structure. At the second step, we applied molecular mechanics calculations to reproduce tip interactions with the lysozyme on the surface. As a result, we have obtained the height as a function of horizontal coordinates. The function was compared with the AFM real experimental surface height function for adsorbed lysozyme. The results of this comparison showed the excellent equivalence in the shape of experimental and modeled lysozyme structures and a significant difference in their sizes. The investigation of this difference led us to the conclusion that more detailed simulations of AFM imaging are needed to reach a better correspondence between the experiment and the model. We consider our approach to be applicable to refine the AFM images of proteins by a visual comparison with the results of simulation based on precise X-ray structures of these proteins. The first results of the application of this approach provide sufficient information on how to improve the accuracy in further applications. PMID- 20586321 TI - [Noninvasive optical laser technologies for the transplantation of mammalian nuclei]. AB - The results of pioneering studies on the development of radically new noninvasive methods for the transplantation of mammalian somatic cell nuclei with the use of optical laser manipulations are presented, and their comparison with traditional invasive methods is performed. It is shown that all the key steps, including the enucleation of a recipient cell, the transfer of a somatic cell (karyoplast), its bringing close together with the recipient cytoplast, and the fusion of the cytoplast with the somatic cell, can be effectively conducted using the laser only with the complete replacement by laser of traditional mechanical micromanipulators and other devices, including devices for electrofusion. The results indicate the unique potentialities of laser and the prospects of its application in modern cell engineering in a wide spectrum of studies on oocytes and early mammalian embryos, in particular in technologies of therapeutic and reproductive cloning. PMID- 20586322 TI - [Mystery and problems of cloning]. AB - The attention of investigators is attracted to the fact that, in spite of great efforts in mammalian cloning, advances that have been made in this area of research are not great, and cloned animals have developmental pathologies often incompatible with life and/or reproduction ability. It is yet not clear what technical or biological factors underlie this, and how they are connected or interact with each other, which is more realistic strategically. There is a great number of articles dealing with the influence of cloning with the nuclear transfer on genetic and epigenetic reprogramming of donor cells. At the same time we can see the practical absence of analytical investigations concerning the technology of cloning as such, its weak points, and possible sources of cellular trauma in the course of microsurgery of nuclear transfer or twinning. This article discusses step by step several nuclear transfer techniques and the methods of dividing early preimplanted embryos for twinning with the aim to reveal possible sources of cell damage during micromanipulation that may have negative influence on the development of cloned organisms. Several new author's technologies based on the study of cell biophysical characteristics are described, which allow one to avoid cellular trauma during manipulation and minimize the possibility of cell damage at any rate. PMID- 20586323 TI - [Comparative embryology and mammalian cloning]. AB - A hypothesis has been advanced that logically combines "contradictory" facts concerning the early mammalian development and shows a natural relationship between the embryos developing from a fertilized ovum and from cells of the inner cell mass of blastocyst. When studying the theoretical questions of cloning, it is necessary to take into consideration the peculiarities of prenatal mammalian ontogenesis, which make themselves evident upon comparison with other animals. The absence of yolk in the mammalian ovum defines sharp differences in the early development between mammals and other Amniota. The whole asynchronic cleavage results in the formation of the morula followed by the blastocyst, which hatches from zona pellucida and is implanted into the uterus tissue. This fact allows us to consider the blastocyst as a mammalian larva, which is fed thanks to maternal organism. It is known that, in the body of a larva (blastocyst), a new embryo develops from some somatic cells. This process is known as a polyembryony, which is typical for the development of some parasitic insects. The polyembryony in turn is a variant of somatic embryogenesis, which is a form of asexual reproduction. Thus, two different embryos, "conceptus" and "embryo proper", have different origin: the first forms by the sexual way and the second, by the asexual. The investigation of the mechanisms of somatic embryogenesis in mammals will help us to find conditions necessary for the full reprograming of donor somatic nuclei and provide the successful development of reconstructed embryos. PMID- 20586324 TI - [A "micromere model" of cellular interactions in sea urchin embryos]. AB - It has been shown that the isolation of sea urchin blastomeres before "pos division adhesion" leads mainly to the formation of similar blastomeres at the stage of the 4th cleavage division, whereas after adhesion it results in the formation of micromeres simultaneously with intact embryos. Similar results were obtained in five sea urchin species. It has been concluded that there exists a critical point in the cleavage process, when blastomeres exchange information that determines further pattern of cleavage. It has been shown on this "micromere model" that serotonin and its analogues influence the cleavage pattern of half embryos. These data served as a basis for the hypothesis of "protosynapse", a double-sided symmetric structure in which both blastomeres are not only source and a target of the signal but also a passive obstacle for the leakage of the signal substance from the interblastomere cleft to the milieu. Such a structure is also able to provide the primary asymmetry of blastomeres. The micromere model may be useful in specific pharmacological screening. PMID- 20586325 TI - [Formation of dinitrosyl iron complexes in cardiac mitochondria]. AB - It has been established that, in the presence of S-nitrosothiols, cysteine, and mitochondria, dinitrosyl iron complexes (DNIC) coupled to low-molecular-weight ligands and proteins are formed. The concentration of DNIC depended on oxygen partial pressure. It was shown that, under the conditions of hypoxia, the kinetics of the formation of low-molecular DNIC was diphasic. After the replacement of anaerobic conditions of incubation to aerobic ones, the level of DNIC came down; in this case, protein dinitrosyl complexes became more stable. We proposed that iron- and sulfur-containing proteins and low-molecular-weight iron complexes are the sources of iron for DNIC formation in mitochondrial suspensions. It was shown that a combination of DNIC and S-nitrosothiols inhibited effectively the respiration of cardiomyocytes. PMID- 20586326 TI - [Mathematical and computation modelling of a self-organizing sarcomere with chaotic dynamics of the order parameter]. AB - The results of constructing a nonlinear model of sarcomere contraction have been summarized. A strange attractor has been obtained, which is related to the randomness of the dynamics of the order parameter during the sarcomere deformation. The hypothesis has been proposed that when actin filaments in the sarcomere are fixed, the myosin system undergoes nonlinear oscillations with dissipation, which leads to temperature increase. The increase in temperature has been determined for pulsations of the inertial range. Normalized spectra of the power of pulsations of the order parameter have been constructed for the model by the Fourier-transform method. The thermodynamics of the contraction of the sarcomere has been considered. PMID- 20586327 TI - [Cell engineering and genetic approaches to the development of models of human embryonic stem cells for studying genetic disorders]. AB - A novel approach to the establishment of genetically modified human embryonic stem cell (hESC) lines has been developed, and it has been shown that mutant hESC may be derived from affected embryos after preimplantation genetic diagnosis screening for a particular single gene disorder. Here we provide the description of embryo and cell manipulation procedures, diagnostic lay out, analysis of the efficiency of embryo development and hESC establishment, as well as developments for hESC derivation in animal free conditions. The high efficiency of the approach (50%) is especially crucial in the work with rare and unique resources, such as genetically screened embryos necessary for the derivation of hESC lines representative of specific genetic diseases. PMID- 20586328 TI - [Analysis of the role of various components of culture media during the proliferation of mouse neuroblastoma NIE-115 cells]. AB - The values of the parameters of serum-free media (concentration of Na+, amino acids, and carbohydrates, as well as the pH values) have been determined at which the rate of the differentiation of neuroblastoma cells is minimal, and the rate of proliferation is maximal. It was shown that media inducing the differentiation of 70% of cells during the cell cycle provide the maximal time of survival of differentiated cells. PMID- 20586329 TI - [Trabeculae and the intertrabelcular tissue during the contraction of the frog atrium at decreased temperatures and sodium ion concentrations in solution]. AB - Data characterizing the kinetics of the contraction of trabeculae and the intertrabelcular tissue have been obtained. It has been concluded that trabeculae can act as conductors/transmitters of contraction across the myocardium and play a leading role in this process, while the functional role of the intertrabelcular tissue is secondary and more passive, and consists in the optimization and support of the contractile process. PMID- 20586330 TI - [Computer simulations of the preautomatic pause in pacemaker cells of the sinoatrial node]. AB - The duration of the preautomatic pause as a function of sinoatrial node, the type of pacemaker cells, acetylcholine concentration, the duration of high-frequency stimulation, and the conductivity of gap junctions has been studied. It was found that the preautomatic pause in peripheral pacemakers occurs at a higher concentration of acetylcholine as compared with central pacemakers. The dependence of the duration of the preautomatic pause on the gap junction conductivity is a nonlinear one. PMID- 20586331 TI - [Investigation of pacemaker shift in the rabbit sinoatrial node using the optical mapping technique]. AB - Changes of the activation sequence in the rabbit sinoatrial node under the influence of low temperature and I(f) selective blocker ivabradine have been studied using the optical mapping technique. Both factors caused a shift of the pacemaker within the sinoatrial node region. These results are compared with the data obtained recently in the investigation of pacemaker shift under the influence of cholinergic and adrenergic factors. Possible mechanisms of the pacemaker shift are discussed. The suppression of electric activity in the central part of the sinoatrial node during the action of acetylcholine, which is called cholinergic inexcitability, may be considered as one of the mechanisms of the pacemaker shift. It is shown that the main cause of cholinergic inexcitability is the activation of potassium acetylcholine-dependent current I(KACh). PMID- 20586333 TI - [Frequency and the mutation spectrum of GJB2-related disorders of hearing in children from Dagestan as compared with the central European part of Russia]. AB - The sequencing of the entire coding region and the donor site of the splicing of the GJB2 gene has shown that prelingual neurosensory nonsyndromic autosomal recessive deafness/poor hearing in Republic Dagestan is genetically more heterogeneous than in the central European part of Russia. Thus, the number of the revealed mutations in the GJB2 gene in Dagestan was only 28% of the total number of alleles in patients tested. The main mutations in the GJB2 gene in Dagestan were represented by three forms typical for West Asia: 35delG mutation (22% of all mutant alleles), deltaE120 mutation (22%), both in the coding region, and IVS 1+1 G > A (44%) in the donor site of splicing. In addition, a novel mutation, deltaE187, was revealed in the coding region. All mutations were found in a compound heterozygous or a heterozygous state. This result allows one to explain the deafness/poor hearing by pathogenic mutations in the GJB2 gene only in 19% of Dagestan families with neurosensory nonsyndromic autosomal recessive disorders of hearing. We suggest that the origin and maintenance of the allele diversity of inherited deafness/poor hearing in Dagestan can be explained by the national and cultural peculiarities of small populations of nations of North Caucasus. PMID- 20586332 TI - [The strategy of the "useful sun" improves physical endurance and structural adaptation in the myocardium]. AB - The action of solar light transformed by special screens has been studied on CD-1 male mice. In the active control group, mice were irradiated through screens absorbing the UV-component. In the experimental group, screens transforming the UV-component into the orange-red light were used. In the active control, changes in the swimming activity, as compared to the same parameter before irradiation, were manifested much less than in animals of the experimental group. A morphological analysis showed changes in the structure of all cardiomyocyte organelles studied: the relative area of mitochondria in the experimental mice increased by more than 20% compared to intact animals (p < 0.05). A significant increase in the area of the sarcoplasmic reticulum, by 23.4% (p < 0.05), and in the volume of the myofibrillar apparatus, by 19.4% (p < 0.05), was detected. The results of our experiment show that the irradiation with using an additional orange-red component improves the physical endurance 1.5 times and initiates morphogenetic processes in cardiac muscle cells. PMID- 20586334 TI - [Various aspects of the pathogenesis of hematogenic osteomyelitis in children]. AB - Characteristic features of the pathogenesis of hematogenous osteomyelitis in children against the background of complex treatment are described. The data characterizing the development of an osteomyelitic focus are presented. Some of the causes of the prolonged course of the disease and its transition into the chronic stage, as well as the aspects of immunobiological protection of the organism in the course of treatment have been studied. PMID- 20586335 TI - [Role of endogenous porphyrins in laser therapy of experimental skin wounds]. AB - The role of endogenous porphyrins in the effect of laser irradiation on the superoxide dismutase (SOD) activity of wound exudate and rat leukocyte activity has been studied on models of aceptic incised skin wounds. Wounds were irradiated by a He-Ne laser (632.8 nm, 1.5 J/cm2) on the 2nd, 3rd, and 4th days after the beginning of the experiment. Irradiation effects were evaluated by the SOD activity (NBT test) and the activity of leukocytes of wound exudate (as a chemiluminescent response to opsonized zymosan). It was found that in animals subjected to laser irradiation, the SOD activity sharply increased. This effect depended on endogenous porphyrin concentration and was retained throughout the experiment. The SOD activity in unirradiated animals decreased from the 2nd to the 5th day of experiment. The evaluation of the activity of wound exudate leukocytes did not reveal any distrinct dependence of the effect on the concentration of endogenous porphyrins. PMID- 20586336 TI - [Dielectric properties of human sweat fluid in the microwave range]. AB - The dielectric properties of sweat fluid gathered from different zones of the human body have been studied in the frequency range from 300 MHz to 3 GHz. It has been shown that the dielectric properties of sweat of different zones differ. The dependence of refraction and absorption indices on the frequency of the signal and the mass concentration of substances dissolved in sweat liquid has been determined. PMID- 20586337 TI - [The influence of geophysical factors on the parameters of human electroencephalogram]. AB - It has been shown that cerebral processes are characterized by fine physiological meteosensitivity. Under ordinary conditions, this manifests itself in correlations between human EEG parameters and the geophysical factors: wind regime, temperature, atmospheric pressure, and relative air humidity. The biometeorological properties of EEG rhythms of a human increase with their increasing frequency in the order delta--theta--alpha--beta irrespective of age. The less the background expressiveness of the neurodynamic process, the higher its meteosensitivity till the certain limit. The lack of a component of the neurodynamic process is filled up by the functional component of another. PMID- 20586338 TI - [Chailakhian's views of the origin of consciousness and mentality]. AB - Chailakhyan's views of sources of the origin of consciousness and mentality have been analyzed. It is supposed that the information interaction alone is not sufficient for the occurrence of consciousness. Something else is necessary that distinguishes a live system from lifeless and can be transmitted to the progeny and evolve. It is assumed that this is an "information-physical interaction", namely, a power profile of conformational reorganizations of proteins during their interaction. L.M. Chailakhyan proves the point of view that this profile during the interaction of proteins cannot be calculated and therefore cannot be cognized. This conclusion is supported by the Godel theorem of incompleteness. PMID- 20586339 TI - [About the origins of some disputable biophysical concepts (what is life from different points of view)]. PMID- 20586340 TI - Assessment of fetal wellbeing. PMID- 20586341 TI - Doppler ultrasound: when and why? PMID- 20586342 TI - Using the biophysical profile to assess fetal wellbeing. PMID- 20586343 TI - Cardiotocography for assessment of fetal wellbeing during labour. PMID- 20586344 TI - Inspiration from Sierra Leone. PMID- 20586345 TI - Cord prolapse: a timely reminder. PMID- 20586346 TI - The newborn physical examination step by step. 1. Eyes. PMID- 20586347 TI - Listeriosis in pregnancy. PMID- 20586348 TI - Craniosacral therapy (2): postnatal care for parents and babies. PMID- 20586349 TI - Shattered expectations. PMID- 20586350 TI - Reaching 50. Fifty maternity units have gone Baby Friendly. PMID- 20586351 TI - Reaching 50. Bristol has become the U.K.'s first Baby Friendly city. PMID- 20586352 TI - Midwifery basics: understanding research (7). Understanding statistics in research papers. PMID- 20586353 TI - Midwives rules and standards: the future. PMID- 20586354 TI - Pinards: essential or outdated? PMID- 20586355 TI - A change in instrument management is on the horizon: wet or dry? PMID- 20586357 TI - Baby's bladder removed by mistake. PMID- 20586358 TI - Psychosocial considerations of perioperative care in children, with a focus on effective management strategies. AB - Children are not just 'small adults'. They have specific physical, psychological and social requirements that must be identified and addressed to optimise their well-being in the perioperative period. The healthcare practitioner should be trained to understand the needs of the paediatric patient in hospital, including the ever increasing need to take into account cultural differences. Hospital policy should include a preoperative preparation programme, specially aimed at the paediatric population, where parental involvement is encouraged throughout. PMID- 20586359 TI - Setting up pre-admission visits for children undergoing day surgery: a practice development initiative. AB - The hospital experience can bring about a range of negative emotions for children. The literature clearly states that children who are prepared for surgery recover faster and have fewer negative effects. Pre-admission programmes seek to prepare children (and their parents) for surgery. This paper describes in detail how a pre-admission programme was established for children and their families who were scheduled for day case surgery. PMID- 20586360 TI - Surgical gowning and gloving. AB - Surgical gowning and gloving is an essential element of perioperative practice and is undertaken by the members of the anaesthetic and surgical teams involved in a perioperative intervention or procedure. Gowning and gloving will take place immediately after surgical hand antisepsis and the whole process is often referred to as scrubbing, gowning and gloving. Surgical hand antisepsis is defined as 'an extension of hand washing' (AfPP 2007), and 'the antiseptic surgical scrub or antiseptic hand rubs performed before donning sterile attire preoperatively' (AORN 2008). The aim of these processes is to improve the perioperative outcome of interventions and procedures by enhancing and further promoting aseptic techniques (ACORN 2006, AfPP 2007). PMID- 20586361 TI - Current practice on preoperative correct site surgical marking. AB - Performing surgery at an incorrect site has devastating outcomes. The National Patient Safety agency and Royal College of Surgeons England have provided recommendations to promote correct site surgery with emphasis on surgical markings. There is little published data on surgical site marking practices amongst surgeons. A prospective audit on surgical site marking was performed on 500 surgical procedures: 204 inguinal hernias, 35 umbilical hernias, 48 varicose veins, 40 toenail removals, 123 excisions of skin lesions, 10 femoral artery procedures and 40 breast procedures. The results showed that 59% of markings were visible in theatre post sterile draping, 40.4% markings were not visible, and 0.6% (3/500) were not marked. Recommendations suggest the use of an arrow with an indelible marker pen. Our results show the use of an arrow in 64% of patients and this was the most common form of mark used. An appropriate marker pen was used on 88% of patients. There is no evident published data to compare our practice to that of other surgical units, however, to improve correct site surgery markings should be visible, recognisable and understood by all specialties and grades. A universal marking system to improve correct site surgery may be beneficial. PMID- 20586362 TI - Nitrous oxide makes me sick: or does it? Nitrous oxide and postoperative nausea and vomiting. AB - This article evaluates whether avoidance of nitrous oxide in general anaesthesia can improve clinical outcomes in surgical patients by reducing postoperative nausea and vomiting, and whether avoidance should become part of a routine clinical management strategy. Despite some controversy, the greatest strength of evidence suggests that avoidance of nitrous oxide may be justified as a pre emptive perioperative strategy as part of a multimodal approach to postoperative nausea and vomiting, especially in those patients known to have a higher baseline risk. PMID- 20586363 TI - Surgical gloves. AB - Surgeons and obstetricians, over the centuries, were only too aware that accidental open injuries during their work, especially in a septic case, could lead to an infected wound, a fulminating illness and often death. Even before the bacterial nature of infection had been established in the mid 19th century, it was still obvious that this dangerous and often fatal condition was caused by the transfer of some poisonous material or 'miasma' from the patient to his surgeon. As long ago as 1758, an obstetrician named Walbaum protected his hands by covering them with sheep's caecum. Others used gloves of cotton, silk and leather. After Charles Goodyear developed the vulcanisation process to stabilise rubber in 1844, this became the material of choice for these rather crude protective gloves. PMID- 20586364 TI - Remembering Dr. Martin Luther King, Jr. PMID- 20586365 TI - International cultural immersion: en vivo reflections in cultural competence. AB - A baccalaureate nursing program developed and implemented an international cultural immersion course in Guatemala to explore the impact of cultural immersion on student nurses' cultural competence. This qualitative descriptive study generated data through in-depth interviews and en vivo reflective journals. The three themes: Navigating daily life, Broadening the lens, and Making a difference, revealed an expanded context and worldview of culture. International service learning seemed to pervade all aspects of the students' experience. Exercises in participant-observation and reflective writing could enhance student self-awareness and their ability to benefit from a cultural immersion course. PMID- 20586366 TI - The missing element: Incorporating culturally-specific clinical practices in HIV prevention programs for African-American females. AB - African American females are disproportionally affected with new cases of HIV. High risk sexual practices contribute significantly to the incidence and prevalence of this public health problem. It is critical for advance practice nurses to acknowledge the relevance of cultural sensitivity when providing optimal care to African-American females. This article describes behavioral change interventions tailored to address cultural and socioeconomic aspects of HIV prevention among African-American females who attend historically black colleges and universities and is relevant for the African-American community at large. PMID- 20586367 TI - The impact of cultural diversity forum on students' openness to diversity. AB - As the population demographics for the United States (U.S.) shift towards increasing diversity, it is essential that nurses provide culturally competent care. Cultural sensitivity has been identified as a major curricular element in the American Association of Colleges of Nursing's (AACN) The Essentials of Baccalaureate Education for Professional Nursing Practice. Thus it is imperative that nursing faculty use effective strategies to help nursing students develop cultural sensitivity and competence. Educational workshops focusing on cultural diversity are usually designed to increase people's cultural sensitivity. The purpose of this study was to assess the effectiveness of a cultural diversity forum on nursing students' cultural sensitivity as measured by their openness to diversity. A convenience sample of students was recruited from a public university in the southeastern United States. The workshop was designed as a forum that combined a keynote presentation, shared meal, and a small group interactional activity. Cultural sensitivity was measured using the Openness to Diversity/Challenge Scale (ODCS), and was administered to students before and after the forum. A convenience sample of 47 students agreed to participate and completed both the pretest and posttest. Following the workshop, the students had more cultural sensitivity as measured by their scores on the ODCS (Wilcoxin Signed-Rank test z= -3.286, p = 0.001). The findings suggested that an educational format like the cultural diversity forum can promote students' cultural sensitivity. Further research needs to continue to focus on the effectiveness of strategies to increase the cultural sensitivity of baccalaureate nursing students. PMID- 20586368 TI - Implementing Ask Me 3 to improve African American patient satisfaction and perceptions of physician cultural competency. AB - OBJECTIVE: Improve African American patient satisfaction and perceptions of physician cultural competency through the implementation of Ask Me 3 pamphlet which encourages patients to ask questions of physicians. METHODS: Intervention participants received the pamphlet prior to their visit with the physician. Analysis evaluated differences in patient satisfaction and perceptions of physician cultural competency between intervention participants and controls. RESULTS: Intervention participants who saw their regular physician reported higher satisfaction. All found the questions to be helpful and reported knowing more about their medical condition or illness after the visit. CONCLUSIONS: The Ask Me 3 pamphlet is a low cost and logistically feasible tool that could be readily implemented in medical settings to facilitate physician-patient interaction. Improved satisfaction with the visit was found when the pamphlet was implemented during visits with a regular physician. Thus, our research findings suggest implementation of the Ask Me 3 pamphlet has the potential to improve health care behaviors and health outcomes and may ultimately lead to a reduction in health care disparities. PMID- 20586369 TI - A longitudinal study of cultural competence among health science faculty. AB - The purpose of this study was to measure the process of cultural competence over time in a group of Health Science Faculty teaching nursing and other allied health students. Faculty (n=28) were administered the Inventory for Assessing the Process of Cultural Competence Among Healthcare Professionals (IAPCC) prior to a cultural competence workshop, immediately after the workshop, and again at three months, six months and 12 months. The mean scores increased significantly with each administration of the IAPCC from the pretest administration (52.17) to the 12 month administration (59.71) demonstrating new knowledge related to cultural competence as a process. PMID- 20586372 TI - Breastfeeding: supporting work throughout the year. PMID- 20586373 TI - Family nurse partnership and health inequalities. PMID- 20586374 TI - Estimated cost of a health visitor-led protocol for perinatal mental health. AB - Anecdotally, protocols, care pathways and clinical guidelines are time consuming to develop and sustain, but there is little research about the actual costs of their development, use and audit.This is a notable gap considering the pervasiveness of such documents that are intended to reduce unacceptable variations in practice by standardising care processes. A case study research design was used to calculate the resource use costs of a protocol for perinatal mental health, part of the core programme for health visitors in a primary care trust in the west of England. The methods were in-depth interviews with the operational lead for the protocol (a health visitor) and documentary analysis. The total estimated cost of staff time over a five-year period (2004 to 2008) was Euro 73,598, comprising Euro 36,162 (49%) for development and Euro 37,436 (51%) for implementation. Although these are best estimates dependent upon retrospective data, they indicate the opportunity cost of staff time for a single protocol in one trust over five years. When new protocols, care pathways or clinical guidelines are proposed, the costs need to be considered and weighed against the benefits of engaging frontline staff in service improvements. PMID- 20586375 TI - Mini-MEND: an obesity prevention initiative in a children's centre. AB - Student health visitors led a Mini-MEND project for families with young children as part of their public health nursing course. The project gave a framework for the students and staff members from the children's centre to stimulate an awareness of health needs and facilitate health enhancing activities in terms of healthy eating and parenting. Reflection on the initiative identified application of the principles of health visiting and the domains of specialist community public health nursing, yet the pressures of current health visiting workloads mean that having developed public health skills to use with groups and communities, they may not be used by newly-qualified health visitors. PMID- 20586376 TI - HPV vaccination: vaccine acceptance, side effects and screening intentions. AB - As part of an evaluation of the introductory campaign of human papilloma virus (HPV) vaccine in a Scottish health board, self-administered questionnaires were offered to all 5007 eligible girls in school following the third dose of HPV to identify side-effects, reasons for non-vaccination and future cervical screening intentions, and 2775 (56.2%) replied. In all, 630 (23.5%) of vaccinated girls reported side effects to the vaccination, about half of which were common injection-site reactions. Main reported reasons for non-vaccination related to perceived inadequate evidence for HPV safety and efficacy, and lack of perceived need or desire to be vaccinated. A total of 2430 (89.2%) of the girls expressed plans to take up cervical screening when older. Reasons for not planning to take up cervical smear were lack of knowledge about cervical screening, anticipated discomfort or embarrassment with the process and no perceived need for a cervical smear. Unvaccinated girls were less likely to report planning to attend for cervical smears in later life (Yates chi-square = 24.30, p < 0.001). The findings emphasise the importance of information on safety and efficacy in future communications about HPV with schoolage girls. The relationship between vaccination and screening intention, and its implications for widening the gap in health inequalities, also requires careful attention in local implementation of the national HPV vaccination programme. PMID- 20586377 TI - Fairness and health. PMID- 20586378 TI - Not blind to danger. PMID- 20586379 TI - Tickling tastebuds. PMID- 20586380 TI - New pay survey: be heard. PMID- 20586381 TI - Survey: more U.S. Adults tap into health information online. PMID- 20586382 TI - It's time to do some 'program PM' on your biomedical operation. PMID- 20586383 TI - Prioritizing equipment for replacement. AB - It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study. PMID- 20586384 TI - Leading the way on healthcare information management. PMID- 20586385 TI - It's about time: how to set priorities and finish the job. PMID- 20586386 TI - Developing a five-year business plan for your department. PMID- 20586387 TI - Using data to help evaluate and justify your staffing needs. PMID- 20586388 TI - Stay on top of potential server problems. PMID- 20586389 TI - Ingenuity and creativity: using reviews to improve service quality. PMID- 20586390 TI - The heart of our work. PMID- 20586391 TI - Electromyography--an overview. PMID- 20586392 TI - Medical device interoperability: overview of key initiatives. AB - "...A seamless flow of information between many disparate devices over a network and to/from intended recipients." Sounds great-where do I sign up? In this article, Bridget Moorman, president of BMoorman Consulting, LLC, shines light on various medical device interoperability initiatives. This is one of those articles to cut out and save. Bridget has great ideas on how to keep track of these efforts, especially tracking how your institution fares in device interoperability. Not only can this help with making quick technology assessments and aid future technology planning, it can help to produce a report to show the C suite where you stand in terms of interoperability. Include information such as what you can and cannot connect with in an "interoperability tracking report". This article is a great summary of these initiatives. Keep in mind that AAMI's proposed new IEC 80001 standard about risk management for IT networks also provides important guidance for ensuring safety of interoperable systems. The standard is expected to be published by the end of 2010. PMID- 20586393 TI - Telemetry via Wi-Fi: a case study. PMID- 20586394 TI - Migrating ultrasound service in-house. PMID- 20586395 TI - Performance improvement: a topic whose time has come--again. PMID- 20586396 TI - The need for proper SPD training. PMID- 20586397 TI - Alarm management: clinical perspective. PMID- 20586398 TI - Achieving customer satisfaction through complaint or feedback. PMID- 20586399 TI - New FDA device director emphasizes importance of interoperability. PMID- 20586400 TI - Epidemiological surveillance using information technologies in Paraguay. AB - This article presents the early work on a project in Paraguay for epidemiological surveillance using information technologies. This project is a response of our university to a governmental request to establish links of cooperation and development between academic public sectors of Spain and Paraguay. The overall project objective is the promotion ofa healthy citizenry through the application of information and communication technologies to the monitoring of populations vulnerable to febrile syndromes (FS). The goal of this project is to create the infrastructure that will allow the population of the country to easily communicate with health centers and provide information on cases of FS. The telephone network will be the main physical support for this communication. The project was formally initiated in January 2009 with the implementation of the prototype system. During the first half of 2010, the pilot project will be implemented in Asuncion, Paraguay. PMID- 20586401 TI - Steam sterilization validation for implementation of parametric release at a healthcare facility. AB - Hospitals are under continual pressure to improve turnaround times for surgical procedures and to find ways to release sterilized product without the need to wait for biological indicator (BI) results. Current procedures used in healthcare do not allow for release of sterilized products based on parameters because hospitals do not validate their sterilization processes. Once a sterilization process is validated for a particular product family, those loads may be released based upon evaluation of the sterilization parameters achieved in the cycle, i.e., parametric release. Typically, hospitals do not perform validation studies to demonstrate that a sterility assurance level (SAL) of 10(-6) is being achieved in the sterilized product, relying instead on inactivation of BIs and/or chemical indicators (CIs) in each load. If a healthcare facility can demonstrate achievement ofa SAL of l0(-6) in a particular product family then it will be possible to release the products in that product family based on achievement of parameters without waiting for BI results. This does not mean that the healthcare facility can eliminate use of all BIs and CIs as part of the criteria for a comprehensive quality assurance program, but dependence on their results and the cost of their use may be greatly reduced. Validation provides another component in a quality assurance program to demonstrate that the highest SAL possible is being provided to patients while still providing the services required by today's healthcare facility. PMID- 20586402 TI - Two questions no one is asking in the debate about PM. PMID- 20586405 TI - Electron affinities, fluoride affinities, and heats of formation of the second row transition metal hexafluorides: MF(6) (M = Mo, Tc, Ru, Rh, Pd, Ag). AB - High-level electronic structure calculations were used to evaluate reliable, self consistent thermochemical data sets for the second row transition metal hexafluorides. The electron affinities, heats of formation, first (MF(6) --> MF(5) + F) and average M-F bond dissociation energies, and fluoride affinities of MF(6) (MF(6) + F(-) --> MF(7)(-)) and MF(5) (MF(5) + F(-) --> MF(6)(-)) were calculated. The electron affinities are higher than those of the corresponding third row hexafluorides, making them stronger one-electron oxidizers. The calculated electron affinities, in good agreement with the available experimental values, are 4.23 eV for MoF(6), 5.89 eV for TcF(6), 7.01 eV for RuF(6), 6.80 eV for RhF(6), 7.95 eV for PdF(6), and 8.89 eV for AgF(6). The corresponding pentafluorides are also very strong Lewis acids, although their acidities on the pF(-) scale are about one unit lower than those of the third row pentafluorides. The performance of a wide range of DFT exchange-correlation functionals was benchmarked by comparing them to our more accurate CCSD(T) results. PMID- 20586406 TI - Extended mapping and exploration of the vanadium dioxide stress-temperature phase diagram. AB - Single-crystal micro- and nanomaterials often exhibit higher yield strength than their bulk counterparts. This enhancement is widely recognized in structural materials but is rarely exploited to probe fundamental physics of electronic materials. Vanadium dioxide exhibits coupled electronic and structural phase transitions that involve different structures existing at different strain states. Full understanding of the driving mechanism of these coupled transitions necessitates concurrent structural and electrical measurements over a wide phase space. Taking advantages of the superior mechanical property of micro/nanocrystals of VO(2), we map and explore its stress-temperature phase diagram over a phase space that is more than an order of magnitude broader than previously attained. New structural and electronic aspects were observed crossing phase boundaries at high-strain states. Our work shows that the actively tuning strain in micro/nanoscale electronic materials provides an effective route to investigate their fundamental properties beyond what can be accessed in their bulk counterpart. PMID- 20586407 TI - Insights into the origins of configurational stability of axially chiral biaryl amines with an intramolecular N-H-N hydrogen bond. AB - Configurationally stable chiral biaryl amines with an intramolecular N-H-N hydrogen bond have been developed. The barriers for racemization are in the range of 19.3-28.2 kcal/mol, which corresponds to the half-lives of racemization of the enantiomers in the range of 7 s to 2 years at 20 degrees C. Enantiomers of some of these compounds were separable by HPLC with chiral stationary phases. The biaryl amines are supposed to have a conformation similar to that of a binaphthyl skeleton, which was indicated by an X-ray crystal analysis of a biaryl amine. The N-H appears at 11.1-13.3 ppm in their (1)H NMR spectrum in CDCl(3), indicating strong hydrogen bonding. Biaryl amines with an extremely strong intramolecular N H-N hydrogen bond (delta(NH) approximately 13 ppm) were assumed to undergo racemization without cleavage of an N-H-N hydrogen bond, while those with a mediumly strong N-H-N hydrogen bond (delta(NH) approximately 11 ppm) are assumed to undergo racemization via cleavage of an N-H-N hydrogen bond. Hydrogen/deuterium exchange of a chiral biaryl amine was found to proceed without any trace of racemization. PMID- 20586408 TI - Mechanism of accumulation and incorporation of organometallic Pd complexes into the protein nanocage of apo-ferritin. AB - Hybridization of metal complexes and protein scaffolds is an important subject in bioinorganic chemistry and materials science. Efforts to provide non-natural functions to proteins will likely lead to advances in development of catalysts, sensors, and so on. Mechanistic investigations of the process of binding of metal complexes within protein scaffolds and characterization of the resulting coordination structures will help us to design and control coordination structures of metal complexes for construction of hybrid proteins containing metal complexes. In this work, the processes of accumulation and incorporation of organometallic palladium complexes within the cage of the iron storage protein apo-ferritin (apo-Fr) are elucidated by analysis of X-ray crystal structures of apo-Fr and selected mutants thereof, in the presence of the metal complexes. The crystal structure of apo-Fr containing Pd(allyl) (allyl = eta(3)-C(3)H(5)) complexes shows that thiolato-bridged dinuclear Pd(allyl) complexes are formed at two binding sites within the cage of apo-Fr. The crystal structures of apo-Fr and its Cys- and His-deletion mutants containing Pd(allyl) complexes indicate that Cys126 accelerates the incorporation of Pd(allyl) complexes into the cage. In addition, Cys48 and Cys126 are essential for accumulation of Pd(allyl) complexes and stabilizing the square planar coordination structure. PMID- 20586409 TI - Transition from isolated to collective modes in plasmonic oligomers. AB - We demonstrate the transition from isolated to collective optical modes in plasmonic oligomers. Specifically, we investigate the resonant behavior of planar plasmonic hexamers and heptamers with gradually decreasing the interparticle gap separation. A pronounced Fano resonance is observed in the plasmonic heptamer for separations smaller than 60 nm. The spectral characteristics change drastically upon removal of the central nanoparticle. Our work paves the road toward complex hierarchical plasmonic oligomers with tailored optical properties. PMID- 20586410 TI - Liquid chromatography electrospray ionization Fourier transform ion cyclotron resonance mass spectrometric characterization of N-linked glycans and glycopeptides. AB - We combine liquid chromatography, electrospray ionization, and Fourier transform ion cyclotron resonance mass spectrometry (LC ESI FT-ICR MS) to determine the sugar composition, linkage pattern, and attachment sites of N-linked glycans. N linked glycans were enzymatically released from glycoproteins with peptide N glycosidase F, followed by purification with graphitized carbon cartridge solid phase extraction and separation over a TSK-Gel Amide80 column under hydrophilic interaction chromatography (HILIC) conditions. Unique glycopeptide compositions were determined from experimentally measured masses for different combinations of glycans and glycopeptides. The method was validated by identifying four peptides glycosylated so as to yield 12 glycopeptides unique in glycan composition for the standard glycoprotein, bovine alpha-2-HS-glycoprotein. We then assigned a total of 137 unique glycopeptide compositions from 18 glycoproteins from fetal bovine serum, and the glycan structures for most of the assigned glycopeptides were heterogeneous. Highly accurate FT-ICR mass measurement is essential for reliable identification. PMID- 20586411 TI - Fluorescence lifetime cross correlation spectroscopy resolves EGFR and antagonist interaction in live cells. AB - Fluorescence correlation or cross-correlation spectroscopy (FCS or FCCS), a single molecule technique, has the ability to provide highly sensitive information on interaction and dynamics of biomolecules both in vitro and in vivo. However, the inherent drawback of FCS is that species with similar molecular weight could not be differentiated. Although FCCS could resolve this through cross-correlation, it suffers from nonideal confocal volume overlap and spectral cross-talk which limits its application. In this work, we demonstrate for the first time the applicability of fluorescence lifetime correlation spectroscopy (FLCS) to monitor the interaction of an antagonist antibody with the epidermal growth factor receptor (EGFR) in live cells. As a proof of concept, we demonstrate the interaction of Cy5 labeled IgG and Alexa633 labeled anti-IgG using a single laser source (636 nm excitation) in vitro. The autocorrelation functions were separated based on their respective lifetime with a single detector and their K(d) value was determined to be 11 +/- 3 nM. An in vivo application constituting the interaction of EGFR neutralizing antibody labeled with Alexa488 and EGFR-GFP in live HEK293 cells was successfully demonstrated. The binding specificity of EGFR neutralizing antibody was confirmed by fluorescence lifetime cross-correlation measurements and fluorescence lifetime imaging (FLIM). The dissociation constant of this complex was found to be 9.2 +/- 2.7 nM. A quantitative assessment of receptor density calculations show that the density of EGFR significantly decreased, from 540 +/- 64 receptors/microm(2) to 38 +/- 7 receptors/microm(2) upon addition of the neutralizing EGFR antibody, indicating that the antagonist could induce receptor internalization. The demonstrated work not only opens up new opportunities in studying protein-protein interactions in solutions and in live cells but also provide new insights in biology to understand how the antagonists influence EGFR through live cell quantification and imaging. PMID- 20586412 TI - Molecular assembly and electropolymerization of 3,4-ethylenedioxythiophene on Au(111) single crystal electrode as probed by in situ electrochemical STM in 0.10 M HClO4. AB - We have used electrochemical scanning tunneling microscopy (EC-STM) to obtain molecular insights on the adlayer structures and electrochemical polymerization of 3,4-ethylenedioxythiophene (EDOT) on a bare Au(111) single crystal electrode in 0.1 M HClO(4) solution. Cyclic voltammetric (CV) studies showed an increase in anodic current at 0.90 V with the oxidation of EDOT monomer occurring at E = 1.10 V (vs reversible hydrogen electrode). In situ STM revealed, for the first time, that EDOT molecules can spontaneously form organized adlayers on a bare Au(111) surface with 18 muM concentration of EDOT in aqueous solution. Molecularly resolved STM images of the EDOT adlayer showed two domains consisting of disordered and ordered structures with the formation of vacancy islands or "etch pits". Several EDOT structures were observed at +0.60 V, namely, (4 x 7), (5 x square root(37)), and (square root(7) x 3) with calculated coverages of 0.107, 0.114, and 0.111 ML, respectively. Electropolymerization was also carried out using in situ STM in 0.10 M HClO(4) under potential control. PMID- 20586413 TI - Synthesis of ultrathin mesoporous carbon through Bergman cyclization of enediyne self-assembled monolayers in SBA-15. AB - In this work, a bottom-up synthesis of ultrathin mesoporous carbon was developed through Bergman cyclization of enediyne containing compounds immobilized inside of SBA-15 nanochannels and followed by pyrolysis. Raman spectroscopy confirmed the occurrence of thermal Bergman cyclization inside the channels. Further heating under elevated temperature produced nanotube arrays in good yield. TEM images revealed the formation of interconnected tubular carbon due to the microtunnels of template. Raman spectra showed moderate degree of graphitization. Formation of enediyne SAMs on a template followed by the processing sequence developed in this work is promising to construct carbon materials with various nanoscopic morphology, such as carbon nanotube, graphene, and giant fullerene. PMID- 20586414 TI - Pt3Ti nanoparticles: fine dispersion on SiO2 supports, enhanced catalytic CO oxidation, and chemical stability at elevated temperatures. AB - A platinum-based intermetallic phase with an early d-metal, Pt(3)Ti, has been synthesized in the form of nanoparticles (NPs) dispersed on silica (SiO(2)) supports. The organometallic Pt and Ti precursors, Pt(1,5-cyclooctadiene)Cl(2) and TiCl(4)(tetrahydrofuran)(2), were mixed with SiO(2) and reduced by sodium naphthalide in tetrahydrofuran. Stoichiometric Pt(3)Ti NPs with an average particle size of 2.5 nm were formed on SiO(2) (particle size: 20-200 nm) with an atomically disordered FCC-type structure (Fm3m; a = 0.39 nm). A high dispersivity of Pt(3)Ti NPs was achieved by adding excessive amounts of SiO(2) relative to the Pt precursor. A 50-fold excess of SiO(2) resulted in finely dispersed, SiO(2) supported Pt(3)Ti NPs that contained 0.5 wt % Pt. The SiO(2)-supported Pt(3)Ti NPs showed a lower onset temperature of catalysis by 75 degrees C toward the oxidation reaction of CO than did SiO(2)-supported pure Pt NPs with the same particle size and Pt fraction, 0.5 wt %. The SiO(2)-supported Pt(3)Ti NPs also showed higher CO conversion than SiO(2)-supported pure Pt NPs even containing a 2 fold higher weight fraction of Pt. The SiO(2)-supported Pt(3)Ti NPs retained their stoichiometric composition after catalytic oxidation of CO at elevated temperatures, 325 degrees C. Pt(3)Ti NPs show promise as a catalytic center of purification catalysts for automobile exhaust due to their high catalytic activity toward CO oxidation with a low content of precious metals. PMID- 20586415 TI - Formation of three-dimensional hydrogel multilayers using enzyme-mediated redox chain initiation. AB - Enzyme-mediated redox chain initiation involving glucose oxidase (GOX) was employed in an iterative solution dip-coating technique to polymerize multiple, three-dimensional hydrogel layers using mild aqueous conditions at ambient temperature and oxygen levels. To the best of our knowledge, sequential enzyme mediated dip-coating resulting in an interfacial radical chain polymerization and subsequent formation of three-dimensional hydrogel layers has not been previously explored. Conformal, micrometer-scale, uniform poly(ethylene glycol) (PEG)-based hydrogel layers were polymerized within seconds and remained securely associated after incubation in water for 16 weeks. Incorporation of either small molecules (i.e., rhodamine-B acrylate, fluorescein acrylate) or fluorescent nanoparticles into crosslinked hydrogel layers during the polymerization reaction was also achieved. The encapsulation of 0.2 microm-diameter nanoparticles into hydrogels during polymerization of a 2-hydroxyethyl acrylate (HEA)/PEG(575) diacrylate monomer formulation, using the GOX-mediated initiation, resulted in minimal effects on polymerization kinetics, with final acrylate conversions of 95% (+/- 1%) achieved within minutes. The temporal control and spatial localization afforded by this interfacial redox approach resulted in the polymerization of uniform secondary layers ranging between 150 (+/- 10) microm and 650 (+/- 10) microm for 15 and 120 s immersion times, respectively. Moreover, increasing the PEG(575)-fraction within the initial hydrogel substrate from 10 to 50% decreased the subsequent layer thicknesses from 690 (+/- 30) microm to 490 (+/- 10) microm because of lowered glucose concentration at the hydrogel interface. The ability to sequentially combine differing initiation mechanisms with this coating approach was achieved by using GOX-mediated interfacial polymerization on hydrogel substrates initially photopolymerized in the presence of glucose. The strict control of layer thicknesses combined with the rapid, water-soluble, and mild polymerization will readily benefit applications requiring formation of stratified, complex, and three-dimensional polymer structures. PMID- 20586417 TI - Novel ELISAs for screening of the biogenic amines GABA, glycine, beta phenylethylamine, agmatine, and taurine using one derivatization procedure of whole urine samples. AB - The inhibitory neurotransmitters GABA, glycine and agmatine and neuromodulators beta-phenylethylamine (beta-PEA) and taurine are important biogenic amines of the sympathetic and parasympathetic nervous systems in the body. Abnormalities in the metabolism of these biomarkers have been implicated in a vast number of neurological diseases. Novel competitive immunoassays, using one unique whole urine derivatization procedure applicable for all five biomarkers, have been developed. The determination of these biomarkers was highly reproducible: the coefficient of variance of inter- and intra-assay variation is between 3.9% and 9.8% for all assays. The assays show a good linearity in urine samples within the range of 100-400 mg Cr/dL and specificity when urine samples are spiked with biogenic amines. The recoveries are between 76 and 154%. The correlation between HPLC and ELISA for glycine and taurine (n = 10) showed regression coefficients of 0.97 and 0.98, respectively. An in vivo study on the urinary clearance of beta PEA, agmatine and taurine after oral intake by healthy individuals demonstrated the specificity and clinical significance of these new immunoassays. The immunoassays are useful for clinical and basic research where a fast and accurate assay for the screening of biogenic amines in urine is required, without preclearance of the sample. PMID- 20586418 TI - Characterization of sulfide compounds in petroleum: selective oxidation followed by positive-ion electrospray Fourier transform ion cyclotron resonance mass spectrometry. AB - A novel analytical method for identifying sulfides in petroleum and its fractions was developed. Sulfides in petroleum were selectively oxidized into sulfoxides using tetrabutylammonium periodate (TBAPI) and identified by positive-ion electrospray ionization (ESI) Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). A variety of model sulfur compounds were examined to evaluate the selective oxidization and ionization efficiencies for sulfur compounds in petroleum. Two fractions, straight-run diesel and saturates of Athabasca oilsands bitumen were investigated using this approach. The oxidization process was highly selective for sulfides from thiophenes and aromatic hydrocarbons. Oxidation generated sulfoxides were ionized by positive-ion ESI and analyzed by FT-ICR MS. Mass spectra revealed the composition characteristics of sulfides in the diesel by contrasting the double bond equivalence (DBE) and carbon number distribution of sulfur compounds before and after oxidation. The abundant sulfides in the straight run diesel and saturates fraction of oilsands bitumen had DBE values of 1-3 and 1-4, respectively. PMID- 20586416 TI - Oriented single-crystal nuclear resonance vibrational spectroscopy of [Fe(TPP)(MI)(NO)]: quantitative assessment of the trans effect of NO. AB - This paper presents oriented single-crystal Nuclear Resonance Vibrational Spectroscopy (NRVS) data for the six-coordinate (6C) ferrous heme-nitrosyl model complex [(57)Fe(TPP)(MI)(NO)] (1; TPP(2-) = tetraphenylporphyrin dianion; MI = 1 methylimidazole). The availability of these data enables for the first time the detailed simulation of the complete NRVS data, including the porphyrin-based vibrations, of a 6C ferrous heme-nitrosyl, using our quantum chemistry centered normal coordinate analysis (QCC-NCA). Importantly, the Fe-NO stretch is split by interaction with a porphyrin-based vibration into two features, observed at 437 and 472 cm(-1). The 437 cm(-1) feature is strongly out-of-plane (oop) polarized and shows a (15)N(18)O isotope shift of 8 cm(-1) and is therefore assigned to nu(Fe-NO). The admixture of Fe-N-O bending character is small. Main contributions to the Fe-N-O bend are observed in the 520-580 cm(-1) region, distributed over a number of in-plane (ip) polarized porphyrin-based vibrations. The main component, assigned to delta(ip)(Fe-N-O), is identified with the feature at 563 cm(-1). The Fe-N-O bend also shows strong mixing with the Fe-NO stretching internal coordinate, as evidenced by the oop NRVS intensity in the 520-580 cm(-1) region. Very accurate normal mode descriptions of nu(Fe-NO) and delta(ip)(Fe-N-O) have been obtained in this study. These results contradict previous interpretations of the vibrational spectra of 6C ferrous heme-nitrosyls where the higher energy feature at approximately 550 cm(-1) had usually been associated with nu(Fe-NO). Furthermore, these results provide key insight into NO binding to ferrous heme active sites in globins and other heme proteins, in particular with respect to (a) the effect of hydrogen bonding to the coordinated NO and (b) changes in heme dynamics upon NO coordination. [Fe(TPP)(MI)(NO)] constitutes an excellent model system for ferrous NO adducts of myoglobin (Mb) mutants where the distal histidine (His64) has been removed. Comparison to the reported vibrational data for wild-type (wt) Mb-NO then shows that the effect of H bonding to the coordinated NO is weak and mostly leads to a polarization of the pi/pi* orbitals of bound NO. In addition, the observation that delta(ip)(Fe-N-O) does not correlate well with nu(N-O) can be traced back to the very mixed nature of this mode. The Fe-N(imidazole) stretching frequency is observed at 149 cm(-1) in [Fe(TPP)(MI)(NO)], and spectral changes upon NO binding to five-coordinate ferrous heme active sites are discussed. The obtained high-quality force constants for the Fe-NO and N-O bonds of 2.57 and 11.55 mdyn/A can further be compared to those of corresponding 5C species, which allows for a quantitative analysis of the sigma trans interaction between the proximal imidazole (His) ligand and NO. This is key for the activation of the NO sensor soluble guanylate cyclase. Finally, DFT methods are calibrated against the experimentally determined vibrational properties of the Fe-N-O subunit in 1. DFT is in fact incapable of reproducing the vibrational energies and normal mode descriptions of the Fe-N-O unit well, and thus, DFT-based predictions of changes in vibrational properties upon heme modification or other perturbations of these 6C complexes have to be treated with caution. PMID- 20586419 TI - Protease-activatable organometal-Peptide bioconjugates with enhanced cytotoxicity on cancer cells. AB - Over the past years, numerous promising new metalorganic lead structures have been developed exhibiting highly active cytostatic properties. However, the efficiency of such chemotherapeutics in the treatment of tumors is often limited by their low therapeutic index due to their short half-life, lack of tumor selectivity, and associated side effects. Furthermore, the membrane barrier often restricts their cellular uptake by passive diffusion. In this contribution, we describe the synthesis, cellular uptake, and biologic activity of a series of cymantrene-peptide conjugates. Cymantrene CpMn(CO)(3) is a robust organometallic group, which is stable in air and water and easy to functionalize. In this work, some new cymantrene derivatives with different linkers between the half-sandwich complex and the carboxylate group were attached to the cell-penetrating peptide sC18 that should act as a transporter for the metal moiety. All conjugates were characterized for their cytotoxic activity on human breast adenocarcinoma cells (MCF-7) and human colon carcinoma cells (HT-29). We found that bioconjugates bearing two cymantrene groups were more active than the monofunctionalized ones. By the introduction of a cathepsin B cleavage site next to the organometallic group, the biologic activity could be in increased even further. Fluorescence microscopy studies and apoptosis assays gave preliminary hints on the mode of action of these systems. PMID- 20586420 TI - Activation and alteration of base selectivity by metal cations in the functionality-transfer reaction for RNA modification. AB - Previously, we reported that the 2-methylidene-1,3-diketone unit of 6 thioguanosine transferred selectively to the amino group of cytosine at pH 7.0 and that its selectivity was changed to the guanine base at pH 9.6. In this study, it was found that the functionality-transfer reaction enhanced selectivity for the guanine base in the presence of divalent transition metal cations such as Ni(2+) and Co(2+) at pH 7.4. PMID- 20586421 TI - Peptide HIV-1 integrase inhibitors from HIV-1 gene products. AB - Anti-HIV peptides with inhibitory activity against HIV-1 integrase (IN) have been found in overlapping peptide libraries derived from HIV-1 gene products. In a strand transfer assay using IN, inhibitory active peptides with certain sequential motifs related to Vpr- and Env-derived peptides were found. The addition of an octa-arginyl group to the inhibitory peptides caused a remarkable inhibition of the strand transfer and 3'-end-processing reactions catalyzed by IN and significant inhibition against HIV replication. PMID- 20586422 TI - A one-step, solvothermal reduction method for producing reduced graphene oxide dispersions in organic solvents. AB - Refluxing graphene oxide (GO) in N-methyl-2-pyrrolidinone (NMP) results in deoxygenation and reduction to yield a stable colloidal dispersion. The solvothermal reduction is accompanied by a color change from light brown to black. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images of the product confirm the presence of single sheets of the solvothermally reduced graphene oxide (SRGO). X-ray photoelectron spectroscopy (XPS) of SRGO indicates a significant increase in intensity of the C=C bond character, while the oxygen content decreases markedly after the reduction is complete. X-ray diffraction analysis of SRGO shows a single broad peak at 26.24 degrees 2theta (3.4 A), confirming the presence of graphitic stacking of reduced sheets. SRGO sheets are redispersible in a variety of organic solvents, which may hold promise as an acceptor material for bulk heterojunction photovoltaic cells, or electromagnetic interference shielding applications. PMID- 20586424 TI - Organic two-step spin-transition-like behavior in a linear S = 1 array: 3' methylbiphenyl-3,5-diyl bis(tert-butylnitroxide) and related compounds. AB - The title compound showed a unique low-dimensional array with S = 1 molecules. The intermolecular antiferromagnetic coupling and intramolecular ferromagnetic coupling are simultaneously present, and accordingly, the S = 1/2 state appeared at 230-350 K between the diamagnetic phase and the paramagnetic S = 1 phase. The solid-solid phase transition occurred in a single-crystal-to-single-crystal manner. The corresponding 3'-methoxy derivative is also presented for comparison. PMID- 20586423 TI - Kinetic and spectroscopic studies of hemin acquisition in the hemophore HasAp from Pseudomonas aeruginosa. AB - The extreme limitation of free iron has driven various pathogens to acquire iron from the host in the form of heme. Specifically, several Gram-negative pathogens secrete a heme binding protein known as HasA to scavenge heme from the extracellular environment and to transfer it to the receptor protein HasR for import into the bacterial cell. Structures of heme-bound and apo-HasA homologues show that the heme iron(III) ligands, His32 and Tyr75, reside on loops extending from the core of the protein and that a significant conformational change must occur at the His32 loop upon heme binding. Here, we investigate the kinetics of heme acquisition by HasA from Pseudomonas aeruginosa (HasAp). The rate of heme acquisition from human met-hemoglobin (met-Hb) closely matches that of heme dissociation which suggests a passive mode of heme uptake from this source. The binding of free hemin is characterized by an initial rapid phase forming an intermediate before further conversion to the final complex. Analysis of this same reaction using an H32A variant lacking the His heme ligand shows only the rapid phase to form a heme-protein complex spectroscopically equivalent to that of the wild-type intermediate. Further characterization of these reactions using electron paramagnetic resonance and resonance Raman spectroscopy of rapid freeze quench samples provides support for a model in which heme is initially bound by the Tyr75 to form a high-spin heme-protein complex before slower coordination of the His32 ligand upon closing of the His loop over the heme. The slow rate of this loop closure implies that the induced-fit mechanism of heme uptake in HasAp is not based on a rapid sampling of the H32 loop between open and closed configurations but, rather, that the H32 loop motions are triggered by the formation of the high-spin heme-HasAp intermediate complex. PMID- 20586425 TI - Phosphomimetic substitution of cytochrome C tyrosine 48 decreases respiration and binding to cardiolipin and abolishes ability to trigger downstream caspase activation. AB - Mammalian cytochrome c (Cytc) transfers electrons from the bc(1) complex to cytochrome c oxidase (CcO) as part of the mitochondrial electron transport chain, and it also participates in type II apoptosis. Our recent discovery of two tyrosine phosphorylation sites in Cytc, Tyr97 in bovine heart and Tyr48 in bovine liver, indicates that Cytc functions are regulated through cell signaling. To characterize the role of Cytc tyrosine phosphorylation in detail using an independent approach, we here overexpressed and purified a Tyr48Glu mutant Cytc, mimicking the in vivo Tyr48 phosphorylation found in cow liver, along with wild type and Tyr48Phe variants as controls. The midpoint redox potential of the phosphomimetic mutant was decreased by 45 mV compared to control (192 vs 237 mV). Similar to Tyr48 in vivo phosphorylated Cytc, direct kinetic analysis of the Cytc reaction with isolated CcO revealed decreased V(max) for the Tyr48Glu mutant by 30% compared to wild type or the Tyr48Phe variants. Moreover, the phosphomimetic substitution resulted in major changes of Cytc functions related to apoptosis. The binding affinity of Tyr48Glu Cytc to cardiolipin was decreased by about 30% compared to wild type or the Tyr48Phe variants, and Cytc peroxidase activity of the Tyr48Glu mutant was cardiolipin-inducible only at high cardiolipin concentration, unlike controls. Importantly, the Tyr48Glu Cytc failed to induce any detectable downstream activation of caspase-3. Our data suggest that in vivo Tyr48 phosphorylation might serve as an antiapoptotic switch and highlight the strategic position and role of the conserved Cytc residue Tyr48 in regulating multiple functions of Cytc. PMID- 20586426 TI - Nanofibers doped with dendritic fluorophores for protein detection. AB - We report a solid-state, nanofiber-based optical sensor for detecting proteins with an anionic fluorescent dendrimer (AFD). The AFD was encapsulated in cellulose acetate (CA) electrospun nanofibers, which were deacetylated to cellulose to generate secondary porous structures that are desirable for enhancing molecular interactions, and thus better signaling. The protein sensing properties of the fibers were characterized by monitoring the fluorescence response of cytochrome c (cyt c), hemoglobin (Hgb), and bovine serum albumin (BSA) as a function of concentration. Effective quenching was observed for the metalloproteins, cyt c and Hgb. The effect was primarily due to energy transfer of the imbedded fluorescent dendrimers to the protein, as both proteins contain heme portions. Electron transfer, caused through the electrostatic effects in the binding of the anionic dendrimer to the positive patches of globular proteins, could be responsible as well. BSA, on the other hand, triggered a "turn-on" response in fluorescence, suggesting the negatively charged BSA reduces the pi-pi stacking of the partially dispersed, negatively charged dendritic fluorophores through repulsion forces, which results in an increase in fluorescence. Stern Volmer constants (K(sv)) of the electrospun fibers were found to be 3.4 x 10(5) and 1.7 x 10(6) M(-1) for cyt c and Hgb, respectively. The reusability of the nanofibers is excellent: the nanofibers demonstrated less than 15% change of fluorescence intensity signal in a 5-cycle test. PMID- 20586428 TI - Flexible, transparent nanocomposite film with a large clay component and ordered structure obtained by a simple solution-casting method. AB - A flexible, transparent nanocomposite (NC) film with 57 wt % inorganic components was obtained by the simple casting of a solution of Laponite and modified organic molecules through a sol-gel reaction. The NC film has solvent resistance and a disco-nematic liquid-crystalline-like structure of Laponite that originates from the cross linking of Laponite by silanol agents and the large amount of Laponite in the film. PMID- 20586427 TI - Influence of the heteroatom size on the redox potentials of selected polyoxoanions. AB - The apparent formal potentials for the one-electron redox process of most Keggin type heteropolytungstates, XW(12)O(40)(q-), have long been shown to linearly depend on their overall negative charges, in the absence of proton interference in the process. However, for a given overall negative charge, these formal potentials are also shown here to depend on the specific central heteroatom X. In the present work, cyclic voltammetry was used to study a large variety of Keggin type anions, under conditions where their comparisons are straightforward. In short, apparent potential values get more negative (the clusters are more difficult to reduce) for smaller central heteroatoms within a given family of Keggin-type heteropolyanions carrying the same overall negative charge. Density functional theory calculations were performed on the same family of Keggin compounds and satisfactorily reproduce these trends. They show that internal XO(4) units affect differently the tungstate oxide cage. The electrostatic potential created by each internal anionic unit in a fragment-like approach (XO(4)(q-)@W(12)O(36)) was analyzed, and it is observed that X atoms of the same group show slight differences. Within each group of the periodic table, X atoms with lower atomic numbers are also smaller in size. The net effect of such a tendency is to produce a more negative potential in the surroundings and thus a smaller capacity to accept electrons. The case of [BW(12)O(40)](5-) illustrates well this conclusion, with the smallest heteroatom of the Keggin series with group III central elements and a very negative reduction potential with respect to the other elements of the same group. Particularly in this case, the electronic structure of the Keggin anion shows the effects of the small size of boron: the highest occupied molecular orbitals of [BW(12)O(40)](5-) appear to be approximately 0.35 eV higher than those in the other clusters of the same charge, explaining that the BO(4) unit is more unstable than AlO(4) or GaO(4) despite carrying the same formal charge. PMID- 20586429 TI - Membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers: selectivity against model bacterial and mammalian membranes. AB - Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and cationic phenylene ethynylene oligomers (OPEs) exhibit broad-spectrum antimicrobial activity, and their main target is believed to be the cell membrane. To understand better how these antimicrobial molecules interact with membranes, a series of PPE-based CPEs and OPEs with different side chains were studied. Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes were used as model membranes. Among the CPEs and OPEs tested, the anionic CPE, PPE-SO(3)(2-) and the smallest cationic OPE-1 are inactive against all vesicles. Other cationic CPEs and OPEs show significant membrane perturbation ability against bacterial membrane mimics but are inactive against a mammalian cell membrane mimic with the exception of PPE-DABCO and two end-only-functionalized OPEs, which also disrupted a mammalian cell membrane mimic. The results suggest that the phospholipid composition of vesicles dominates the interaction of CPE and OPE with lipid membranes. PMID- 20586431 TI - Deactivation mechanisms of Ni-based tar reforming catalysts as monitored by X-ray absorption spectroscopy. AB - Deactivation mechanisms of alumina-supported, Ni-based catalysts for tar reforming in biomass-derived syngas were evaluated using extended X-ray absorption fine structure (EXAFS) spectroscopy. Catalysts were characterized before and after catalytic reaction cycles and regeneration procedures, which included oxidation by a mixture of steam and air, and reduction in hydrogen. Qualitative analysis of the EXAFS spectra revealed that oxidation of a portion of the Ni in the catalysts to form an oxide phase and/or a sulfide phase were likely scenarios that led to catalyst deactivation with time-on-stream and with increased reaction cycles. Deactivation through carbon deposition, phosphorus poisoning, or changes in particle size were deemed as unlikely causes. Quantitative analysis of the EXAFS spectra indicated sulfur poisoning occurred with time-on-stream, and the contaminating species could not be completely removed during the regeneration protocols. The results also verified that Ni containing oxide phases (most likely a spinel also containing Mg and Al) formed and contributed to the deactivation. This study validates the need for developing catalyst systems that will protect Ni from sulfur poisoning and oxide formation at elevated reaction and regeneration temperatures. PMID- 20586430 TI - Elucidation of the functional metal binding profile of a Cd(II)/Pb(II) sensor CmtR(Sc) from Streptomyces coelicolor. AB - Metal homeostasis and resistance in bacteria is maintained by a panel of metal sensing transcriptional regulators that collectively control transition metal availability and mediate resistance to heavy metal xenobiotics, including As(III), Cd(II), Pb(II), and Hg(II). The ArsR family constitutes a superfamily of metal sensors that appear to conform to the same winged helical, homodimeric fold, that collectively "sense" a wide array of beneficial metal ions and heavy metal pollutants. The genomes of many actinomycetes, including the soil dwelling bacterium Streptomyces coelicolor and the human pathogen Mycobacterium tuberculosis, encode over ten ArsR family regulators, most of unknown function. Here, we present the characterization of a homologue of M. tuberculosis CmtR (CmtR(Mtb)) from S. coelicolor, denoted CmtR(Sc). We show that CmtR(Sc), in contrast to CmtR(Mtb), binds two monomer mol equivalents of Pb(II) or Cd(II) to form two pairs of sulfur-rich coordination complexes per dimer. Metal site 1 conforms exactly to the alpha4C site previously characterized in CmtR(Mtb) while metal site 2 is coordinated by a C-terminal vicinal thiolate pair, Cys110 and Cys111. Biological assays reveal that only Cd(II) and, to a lesser extent, Pb(II) mediate transcriptional derepression in the heterologous host Mycobacterium smegmatis in a way that requires metal site 1. In contrast, mutagenesis of metal site 2 ligands Cys110 or Cys111 significantly reduces Cd(II) responsiveness, with no detectable effect on Pb(II) sensing. The implications of these findings on the ability to predict metal specificity and function from metal-site signatures in the primary structure of ArsR family proteins are discussed. PMID- 20586432 TI - Broadband absorbing bulk heterojunction photovoltaics using low-bandgap solution processed quantum dots. AB - We describe bulk heterojunction (BHJ) solar cells containing blends of colloidal PbS nanocrystal quantum dots with several new donor-acceptor conjugated polymers. Using photoinduced absorption spectroscopy we found that blends of PbS quantum dots with one polymer, poly(2,3-didecyl-quinoxaline-5,8-diyl-alt-N octyldithieno[3,2-b:2',3'-d]pyrrole) (PDTPQx), produce significantly more photoinduced charge than blends of PbS with the other donor-acceptor polymers or with traditionally studied polymers like [2-methoxy-5-(3',7'-dimethyloctyloxy) para-phenylene vinylene] (MDMO-PPV) and poly(3-hexylthiophene) (P3HT). Photovoltaic devices made with PDTPQx/PbS blends exhibit power conversion efficiencies 10-100 times larger than previously reported BHJ blends made with IR absorbing quantum dots. PMID- 20586433 TI - Nanoscale switching characteristics of nearly tetragonal BiFeO3 thin films. AB - We have investigated the nanoscale switching properties of strain-engineered BiFeO(3) thin films deposited on LaAlO(3) substrates using a combination of scanning probe techniques. Polarized Raman spectral analysis indicates that the nearly tetragonal films have monoclinic (Cc) rather than P4mm tetragonal symmetry. Through local switching-spectroscopy measurements and piezoresponse force microscopy, we provide clear evidence of ferroelectric switching of the tetragonal phase, but the polarization direction, and therefore its switching, deviates strongly from the expected (001) tetragonal axis. We also demonstrate a large and reversible, electrically driven structural phase transition from the tetragonal to the rhombohedral polymorph in this material, which is promising for a plethora of applications. PMID- 20586434 TI - NovoFLAP: A ligand-based de novo design approach for the generation of medicinally relevant ideas. AB - NovoFLAP is a computer-aided de novo design tool that generates medicinally relevant ideas for ligand-based projects. The approach combines an evolutionary algorithm (EA-Inventor) with a powerful ligand-based scoring function that uses both molecular shape and pharmacophore features in a multiconformational context (FLAP). We demonstrate that NovoFLAP can generate novel ideas that are not only appealing to design scientists but are also validated by comparison to compounds known to demonstrate activity at the desired biological target. NovoFLAP provides a novel computer-aided design technique that can be used to generate ideas that maintain desirable molecular attributes, such as activity at the primary biological target, while offering opportunities to surmount additional design challenges. Application to the design of the first nonbasic 5HT(1B) antagonist is presented. PMID- 20586435 TI - Novel pathways for enhancing nonlinearity of organics utilizing metal clusters. AB - We show that ultrasmall metallic nanoparticles can be combined with large second- and third-order response organic chromophores to enhance the overall third-order response of the system. This approach can be used in combination with microscopic cascading to generate exceptionally large third-order response. Intermolecular charge-transfer coupling between the molecules and the metal clusters enhances the real part of the nonlinearity at telecommunication wavelengths, while avoiding plasmonic enhancement of one- and two-photon absorption, and minimizing optical losses. The results of density functional calculations for a molecule with large second-order response, (para)nitroaniline, show that use of a gold cluster as a link between molecular entities enhances third-order nonlinearity. Varying size and shape of the metal cluster as well as the distance between the clusters and the molecules allows fine-tuning of nonlinear response over a large range of magnitudes. PMID- 20586436 TI - Tetracyclic chromane derivatives from Rhododendron anthopogonoides. AB - Four new chromane derivatives, anthopogochromane (1), anthopogochromene A (2), anthopogochromene B (3), and anthopogochromene C (4), and two known compounds, daurichromenic acid (5) and ilicicolinic acid B (6), have been isolated from the Chinese medicinal plant Rhododendron anthopogonoides. The S absolute configuration of the stereogenic carbons in the chromane and chromene rings of 1 4 was determined from their circular dichroism spectra. Compounds 1 and 2 inhibited compound 48/80-induced histamine release from rat peritoneal mast cells. PMID- 20586437 TI - An alternative hierarchy of electron correlation beyond the electron pair approximation. AB - Starting from the Nakatsuji theorem, a hierarchy of approximations is considered that begins with traditional coupled cluster theory with singles and doubles (CCSD) and proceeds via the ansatz of semigeneralized singles and doubles (CCSGSD), with operators of the types a(ab)(ic) and a(ka)(ij) included, to the generalized singles and doubles (CCGSD) ansatz with the full basis {a(pq)(rs); a(p)(q)}, and if necessary, beyond. The simplest realization of CCSGSD is the constrained coupled cluster ansatz with singles, doubles, and triples (CCCSDT). It is related to traditional coupled cluster with singles, doubles, and triples (CCSDT), but it requires (for sufficiently large n) a smaller number of parameters of O(nm3) vs O(n3m3) in CCSDT, n being the number of electrons and m the size of the basis. A linear system of equations for the CCCD[T] approximation is derived and strategies toward its solution are discussed. PMID- 20586438 TI - Total synthesis of (-)-8-deoxyserratinine via an efficient Helquist annulation and double N-alkylation reaction. AB - The first enantioselective total synthesis of (-)-8-deoxyserratinine has been achieved in 15 steps from enone 4 with 7% overall yield. The key features include a highly efficient Helquist annulation to furnish the cis-fused 6/5 bicycle, facile construction of the aza nine-membered ring system employing double N alkylation strategy, as well as asymmetric Shi epoxidation, delivering the desired beta-epoxide stereospecifically. PMID- 20586439 TI - Hydrogen-bond structure at the interfaces between water/poly(methyl methacrylate), water/poly(methacrylic acid), and water/poly(2 aminoethylmethacrylamide). AB - The molecular dynamics approach was employed to study the structural characteristics at the interface of water/poly(methyl methacrylate) (PMMA), water/poly(methacrylic acid) (PMAA), and poly(2-aminoethylmethacrylamide) (PAEMA). It is found that the water on the PMAA surface shows a significant increase in the density at the interface, with a greater number of water molecules permeating into the bulk of the substrate region. The structure of hydrogen bonds of water and the radial distribution function for given polar atoms in the polymer substrate are calculated. We found that a network structure of hydrogen bonding between water and the polar atom of the polymer forms at the interface. PMAA exhibits a more hydrophilic property than PMMA and PAEMA because it generates a shell-like structure of water molecules around its functional group. Finally, the hydrogen bond numbers of PMMA, PMAA, and PAEMA are also analyzed. The results detail the hydrogen bond structure of each specific atom and find that, in all three cases, the carboxyl oxygen attracts the greatest number of water molecules compared with other atoms. PMID- 20586440 TI - 1,3,6,8-tetrasubstituted pyrenes: solution-processable materials for application in organic electronics. AB - A series of star-shaped organic semiconductors have been synthesized from 1,3,6,8 tetrabromopyrene. The materials are soluble in common organic solvents allowing for solution processing of devices such as light-emitting diodes (OLEDs). One of the materials, 1,3,6,8-tetrakis(4-butoxyphenyl)pyrene, has been used as the active emitting layer in simple solution-processed OLEDs with deep blue emission (CIE = 0.15, 0.18) and maximum efficiencies and brightness levels of 2.56 cd/A and >5000 cd/m(2), respectively. PMID- 20586441 TI - Synthesis, characterization, and binding property of isoelectronic analogues of nucleobases, B(6)-substituted 5-aza-6-borauracils and -thymines. AB - As isoelectronic BN-containing analogues of 6-substituted uracil and thymine, a series of B(6)-substituted 5-aza-6-borauracils (U(BN)s) and -thymines (T(BN)s) were synthesized and fully characterized. The crystallographic and spectroscopic analyses of the analogues revealed that the framework and hydrogen-bonding pattern of T(BN)s were similar to those of the original nucleobase, thymine. PMID- 20586442 TI - An efficient one-pot synthesis of symmetrical diselenides or ditellurides from halides with CuO nanopowder/Se0 or Te0/base. AB - A CuO nanopowder-catalyzed coupling reaction of aryl, alkyl, and heteroaryl iodides with elemental selenium and tellurium takes place in the presence of KOH at 90 degrees C in DMSO. A wide range of substituted symmetrical diselenides and ditellurides were afforded with good to excellent yields. PMID- 20586443 TI - Mechanistic toxicity assessment of nanomaterials by whole-cell-array stress genes expression analysis. AB - This study performed mechanistic toxicity assessment of nanosilver (nAg) and nanotitanium dioxide anatase (nTiO2_a) via toxicogenomic approach, employing a whole-cell-array library consisting of 91 recombinated Escherichia coli K12 strains with transcriptional GFP-fusions covering most known stress response genes. The results, for the first time, revealed more detailed transcriptional information on the toxic mechanism of nAg and nTiO2_a, and led to a better understanding of the mode of action (MOA) of metal and metal oxide nanomaterials (NMs). The detailed pathways network established for the oxidative stress system and for the SOS (DNA damage) repair system based on the temporal gene expression profiling data revealed the relationships and sequences of key genes involved in these toxin response systems. Both NMs were found to cause oxidative stress as well as cell membrane and transportation damage. Genotoxicity and DNA damage were also observed, although nTiO2_a induced SOS response via previously identified pathway and nAg seemed to induce DNA repair via a pathway different from SOS. We observed that the NMs at lower concentration tend to induce more chemical specific toxicity response, while at higher concentrations, more general global stress response dominates. The information-rich real-time gene expression data allowed for identification of potential biomarkers that can be employed for specific toxin detection and biosensor developments. The concentration-dependent gene expression response led to the determination of the No Observed Transcriptional Effect Level (NOTEL) values, which can be potentially applied in the regulatory and risk assessment framework as an alternative toxicity assessment end point. PMID- 20586444 TI - Comment on "New experimental data and mechanistic studies on the bromate-dual substrate-dual catalyst batch oscillator". PMID- 20586445 TI - Odorant emissions from intensive pig production measured by online proton transfer-reaction mass spectrometry. AB - Emission of odorous compounds from intensive livestock production is a cause of nuisance in populated rural areas. Knowledge on the chemical composition of odor and temporal variations in emissions are needed in order to identify factors of importance for emission rates and select proper abatement technologies. In this work, a method based on proton-transfer-reaction mass spectrometry (PTR-MS) has been developed and tested for continuous measurements of odorant emissions from intensive pig production facilities. The method is assessed to cover all presently known important odorants from this type of animal production with adequate sensitivity and a time resolution of less than one minute. The sensitivity toward hydrogen sulfide is demonstrated to exhibit a pronounced humidity dependency, which can be included in the calibration procedure in order to achieve quantitative results for this compound. Application of the method at an experimental pig facility demonstrated strong temporal variations in emissions, including diurnal variation. Based on these first results, air exchange and animal activity are suggested to be of importance for emission rates of odorants. Highest emissions are seen for hydrogen sulfide and acetic acid, whereas key odorants are evaluated from tabulated odor threshold values to be hydrogen sulfide, methanethiol, 4-methylphenol, and butanoic acid. PMID- 20586446 TI - Mixed polybrominated/chlorinated dibenzo-p-dioxins and dibenzofurans in stack gas emissions from industrial thermal processes. AB - Very little is known about mixed polybrominated/chlorinated dibenzo-p-dioxins and dibenzofurans (PBCDD/F) in industrial thermal processes. In this study, the occurrences and characteristics of PBCDD/F from various incineration and metallurgical processes were investigated. In addition, PBCDD/F analytical protocols based on HRGC/HRMS were developed and optimized. The sum of isomer group concentrations ranged from 1.7-3740 pmol Nm(-3) for PBCDF and 0.2-582 pmol Nm(-3) for PBCDD. For some metallurgical industries, the amounts of PBDD/F and PBCDD/F emitted were similar to or even higher than the amounts of PCDD/F. The sources of bromine and brominated-precursors in these processes should be evaluated. The PBCDD/F characteristics investigated included isomer group patterns, ratio of bromine and chlorine incorporated in PBCDD/F, and ratio of halogenated furans to dioxins. Lower brominated PBCDD/F were binomially distributed. But in some cases, the concentrations of higher brominated PBCDD/F were much higher than predicted from the binomial distribution. The formation mechanisms of PBDD/F, PBCDD/F, and PCDD/F in these processes were also evaluated. PMID- 20586447 TI - Long-term measurements of NO3 radical at a semiarid urban site: 2. Seasonal trends and loss mechanisms. AB - This study is the first to present long-term measurements of the nitrate radical in an urban location. Extensive nitrate radical measurements were conducted together with ancillary parameters during a continuous two year campaign (2005 2007) in the semiarid location of Jerusalem. The average nighttime NO3 concentration was 27.3+/-43.5 ppt, the highest ever reported, with a seasonal average peak during summer (33.3+/-55.8 pptv) with maximum levels exceeding 800 pptv. Significant diurnal changes in NO3 concentrations were observed, caused by an unusual nighttime increase in ozone concentrations. The NO3 loss processes exhibited strong seasonal variability. Homogeneous gas-phase losses were the main removal processes during summer and spring. The heterogeneous losses of N2O5, averaged over the entire campaign, contributed to less than half of the direct losses even though they dominated the winter seasons and part of the autumn months. Statistical regression analysis showed that NO3 was inversely correlated with relative humidity and positively correlated with temperature and to a lesser extent with NO2 and O3, indicating that the heterogeneous removal processes were also important. The diurnal behavior of NO3 was examined using a one-dimensional chemical transport model. The simulations showed that NO3 trends and concentrations were influenced mainly by changes in ozone and nitrogen oxide levels and that the very high levels of NO3 can be explained by the entrainment of fresh ozone from the upper atmospheric levels. After sunset and in the early morning, the homogeneous processes are the major loss pathways, while the heterogeneous N2O5 removal pathway dominates the intermediate times. PMID- 20586448 TI - Silanization of Ag-deposited magnetite particles: an efficient route to fabricate magnetic nanoparticle-based Raman barcode materials. AB - Silica-coated Ag nanostructures usable as magnetic nanoparticle-based Raman barcode materials were developed. Initially, 283 nm sized spherical magnetite particles composed of 13 nm sized superparamagnetic Fe(3)O(4) nanoparticles were synthesized, and silver deposition was conducted using butylamine as the reductant of AgNO(3) in ethanol. The Ag-deposited Fe(3)O(4) (Fe(3)O(4)@Ag) particles are found to be efficient surface-enhanced Raman scattering (SERS) substrates with the enhancement factor at 632.8 nm excitation to be about 3 x 10(6). After SERS markers such as benzenethiol, 4-mercaptotoluene, 4 aminobenzenethiol, and 4-nitrobenzenethiol were adsorbed onto the silver surface, poly(allylamine hydrochloride) (PAH) was coated onto them using the layer-by layer deposition method such that a subsequent base-catalyzed silanization could readily form a 60 nm thick silica shell around the PAH layer by a biomimetic process. The cross-linked silica shells effectively prevented the SERS-marker molecules from being liberated from the surface of the Fe(3)O(4)@Ag particles. Although the gram magnetization decreased nearly to one-half of the initial value because of coating with silver and silica, the remaining magnetization was nonetheless strong enough for the silica-coated Fe(3)O(4)@Ag particles to be used as barcode materials operating via SERS. PMID- 20586449 TI - Anisotropic and inhomogeneous magnetic interactions observed in all-organic nitroxide radical liquid crystals. AB - An anisotropic and inhomogeneous magnetic interaction (the average spin-spin interaction constant (-)J > 0) was observed in the various liquid crystalline (LC) phases of racemic and nonracemic all-organic radical LC compounds 1a and 1b. We discussed how the LC superstructures induced the magnetic interaction to operate in the LC phases in terms of spin-spin dipole and exchange interactions by means of VT-EPR spectroscopy. The magnitude of the magnetic interaction depended on the type of LC phase, or the superstructure. Furthermore, these radical LC droplets floating on water were commonly attracted to a permanent magnet and moved freely under the influence of this magnet, whereas the crystallized particles of the same compounds never responded to the magnet. The response of the LC droplets to the magnet also varied depending on the type of LC phase, that is, the extent of the magnetic interaction. PMID- 20586451 TI - Microfluidic permeation printing of self-assembled monolayer gradients on surfaces for chemoselective ligand immobilization applied to cell adhesion and polarization. AB - To study complex cell behavior on model surfaces requires biospecific interactions between the interfacing cell and material. Developing strategies to pattern well-defined molecular gradients on surfaces is difficult but critical for studying cell adhesion, polarization, and directed cell migration. We introduce a new strategy, microfluidic SPREAD (Solute PeRmeation Enhancement And Diffusion) for inking poly(dimethylsiloxane) (PDMS) microfluidic cassettes with a gradient of alkanethiol. Using SPREAD, an oxyamine-terminated alkanethiol is able to permeate into a PDMS microfluidic cassette, creating a chemical gradient, which can subsequently be transfer printed onto a gold surface to form the corresponding chemoselective gradient of oxyamine-alkanethiol self-assembled monolayer (SAM). By first patterning regions of the gold surface with a protective SAM using microfluidic lithography, directional gradients can be stamped exclusively onto unprotected bare gold regions to form single cell gradient microarrays. The microfluidic SPREAD strategy can also be extended to print micrometer-sized islands of radial SAM gradients with excellent geometric resolution. The immobilization of a cell adhesive Arg-Gly-Asp (RGD)-ketone peptide to the SPREAD stamped oxyamine-alkanethiol SAMs provides a stable interfacial oxime linkage for biospecific studies of cell adhesion, polarity, and migration. PMID- 20586452 TI - Solution synthesis of a new thermoelectric Zn(1+x)Sb nanophase and its structure determination using automated electron diffraction tomography. AB - Engineering materials with specific physical properties have recently focused on the effect of nanoscopic inhomogeneities at the 10 nm scale. Such features are expected to scatter medium- and long-wavelength phonons thereby lowering the thermal conductivity of the system. Low thermal conductivity is a prerequisite for effective thermoelectric materials, and the challenge is to limit the transport of heat by phonons, without simultaneously decreasing charge transport. A solution-phase technique was devised for synthesis of thermoelectric "Zn(4)Sb(3)" nanocrystals as a precursor for phase segregation into ZnSb and a new Zn-Sb intermetallic phase, Zn(1+delta)Sb, in a peritectoid reaction. Our approach uses activated metal nanoparticles as precursors for the synthesis of this intermetallic compound. The small particle size of the reactants ensures minimum diffusion paths, low activation barriers, and low reaction temperatures, thereby eliminating solid-solid diffusion as the rate-limiting step in conventional bulk-scale solid-state synthesis. Both phases were identified and structurally characterized by automated electron diffraction tomography combined with precession electron diffraction. An ab initio structure solution based on electron diffraction data revealed two different phases. The new pseudo-hexagonal phase, Zn(1+delta)Sb, was identified and classified within the structural diversity of the Zn-Sb phase diagram. PMID- 20586450 TI - Hairpin DNA-functionalized gold colloids for the imaging of mRNA in live cells. AB - A strategy is presented for the live cell imaging of messenger RNA using hairpin DNA-functionalized gold nanoparticles (hAuNP). hAuNP improve upon technologies for studying RNA trafficking by their efficient internalization within live cells without transfection reagents, improved resistance to DNase degradation, low cytotoxicity, and the incorporation of hairpin DNA molecular beacons to confer high specificity and sensitivity to the target mRNA sequence. Furthermore, the targeted nanoparticle-beacon construct, once bound to the target mRNA sequence, remains hybridized to the target, enabling spatial and temporal studies of RNA trafficking and downstream analysis. Targeted hAuNP exhibited high specificity for glyceraldehyde 3-phosphate dehydrogenase (GADPH) mRNA in live normal HEp-2 cells and respiratory syncytial virus (RSV) mRNA in live RSV-infected HEp-2 cells with high target to background ratios. Multiplexed fluorescence imaging of distinct mRNAs in live cells and simultaneous imaging of mRNAs with immunofluorescently stained protein targets in fixed cells was enabled by appropriate selection of molecular beacon fluorophores. Pharmacologic analysis suggested that hAuNP were internalized within cells via membrane-nanoparticle interactions. hAuNP are a promising approach for the real-time analysis of mRNA transport and processing in live cells for elucidation of biological processes and disease pathogenesis. PMID- 20586453 TI - Metal-interrupted perylene diimide: toward a new class of tunable n-type inorganic-organic hybrid semiconductors. AB - In organic thin-film transistors (OTFTs), organic electron-transport materials (n type semiconductors) are well behind the advances in development of hole transport materials (p-type semiconductors). Currently, one class of organic n type semiconductor materials that is widely utilized is N,N'-dialkyl-3,4,9,10 perylenetetracarboxylic diimide (PTCDI-R) derivatives with high electron affinities (EAs), such as N,N'-dioctyl-3,4,9,10-perylenetetracarboxylic diimide with a reported EA as high as 4.4 eV. The PTCDI-R derivatives have been manipulated by adding substituents on the perylene moiety or at the amine position to afford more stable compounds and higher EAs. On the basis of these materials, we have developed metal-containing perylenediimide analogues, placing a salpen ligand for metal ion chelation between two n-isobutylnaphthalimides. We demonstrate here that the electronic properties of this class of materials can be systematically tuned in a divergent manner by simply changing the metal center. The synthesis, characterization, electrochemistry, and band-gap analysis are discussed herein. PMID- 20586454 TI - From furans to phosphinines. AB - The reaction between methylenechlorophosphine-pentacarbonyltungsten and furan affords a [4 + 2] adduct whose oxygen bridge is broken by BBr(3), leading to a 2 alkoxyphosphinine after two additional steps. PMID- 20586455 TI - Synthesis of the guaianolide ring system via cycloaddition of a bicyclic carbonyl ylide with allyl propiolate. AB - A cyclic carbonyl ylide with a trans-annulated cyclopentane ring was generated by a Rh(2)(OAc)(4)-catalyzed reaction from a diazoketone precursor and trapped with allyl propiolate. The 1,3-dipolar cycloaddition led to the stereoselective formation of an oxygen-bridged polycycle. Via Curtius degradation, the cycloadduct was transformed to the ring skeleton typical of the sesquiterpene family of guaianolides. PMID- 20586456 TI - A cope rearrangement-based route to hexahydroazulenes. AB - 2-exo-Vinyl-7-alkylidenenorbornanes, readily prepared from fulvene Diels-Alder adducts, undergo smooth Cope rearrangement at elevated temperatures to produce hexahydroazulene derivatives. PMID- 20586457 TI - Development of an enzyme-linked immunosorbent assay to detect benzylpenicilloic acid, a degradation product of penicillin G in adulterated milk. AB - To avoid detection of penicillin G, some producers/merchants illegally add beta lactamase to milk to degrade it into benzylpenicilloic acid (BPA). This degradation product can cause allergic reactions in humans and, therefore, is a potential hazard to human health. To detect BPA in milk, we established a rapid direct competitive enzyme-linked immunosorbent assay (ELISA) with an IC(50) of 0.32 +/- 0.01 microg L(-1), and a detection limit of 0.030 +/- 0.002 microg L( 1). Matrix effects in the milk samples were easily eliminated by centrifugation and dilution. Recoveries were 72.75-93.25%. Also heat treatments of raw milk did not affect the detection of the BPA. To validate BPA-ELISA, the spiked milk samples were analyzed by ELISA and LC-MS; the results showed a strong correlation (r(2) = 0.99). Incurred samples obtained from Tianjin Entry-Exit Inspection and Quarantine Bureau (TJCIQ) were tested by BPA-ELISA. The results showed an almost 100% correlation (r(2) = 0.99) with the results supplied by the TJCIQ. PMID- 20586458 TI - Herbicide-resistant crops: utilities and limitations for herbicide-resistant weed management. AB - Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and cotton growers use to manage weeds. The use of GR crops continues to grow, but weeds are adapting to the common practice of using only glyphosate to control weeds. Growers using only a single mode of action to manage weeds need to change to a more diverse array of herbicidal, mechanical, and cultural practices to maintain the effectiveness of glyphosate. Unfortunately, the introduction of GR crops and the high initial efficacy of glyphosate often lead to a decline in the use of other herbicide options and less investment by industry to discover new herbicide active ingredients. With some exceptions, most growers can still manage their weed problems with currently available selective and HR crop-enabled herbicides. However, current crop management systems are in jeopardy given the pace at which weed populations are evolving glyphosate resistance. New HR crop technologies will expand the utility of currently available herbicides and enable new interim solutions for growers to manage HR weeds, but will not replace the long-term need to diversify weed management tactics and discover herbicides with new modes of action. This paper reviews the strengths and weaknesses of anticipated weed management options and the best management practices that growers need to implement in HR crops to maximize the long-term benefits of current technologies and reduce weed shifts to difficult-to-control and HR weeds. PMID- 20586459 TI - Geometry optimization of radicaloid systems using improved virtual orbital complete active space configuration interaction (IVO-CASCI) analytical gradient method. AB - The improved virtual orbital (IVO) complete active space (CAS) configuration interaction (IVO-CASCI) method is a simplified CAS self-consistent field (SCF), CASSCF, method. Unlike the CASSCF approach, the IVO-CASCI method does not require iterations beyond an initial SCF calculation, rendering the IVO-CASCI scheme computationally more tractable than the CASSCF method and devoid of the convergence problems that sometimes plague CASSCF calculations as the CAS size increases, while retaining all the essential positive benefits of the CASSCF method. Earlier applications demonstrate that the IVO-CASCI energies are at least as accurate as those from the CASSCF and provide the impetus for our recent development of the analytical derivative procedures that are necessary for a wide applicability of the IVO-CASCI approach. Here we test the ability of the analytic energy gradient IVO-CASCI approach (which can treat both closed- and open-shell molecules of arbitrary spin multiplicity) to compute the equilibrium geometries of four organic radicaloid species, namely, (i) the diradicals trimethylenemethane (TMM), 2,6-pyridyne, and the 2,6-pyridynium cation and (ii) a triradical 1,2,3-tridehydrobenzene (TDB), using various basis sets and different choices for the active space. Although these systems and related molecules have fascinated theoretical chemists for many years, their strong multireference character makes their description quite difficult with most standard many-body approaches. Thus, they provide ideal tests to assess the performance of the IVO CASCI method. The present work demonstrates consistent agreement with far more expensive benchmark state-of-the-art ab initio calculations and thereby indicates that this new gradient method is able to describe the geometries of various radicaloids very accurately, even when small, but qualitatively correct, reference spaces are used. For example, the IVO-CASCI method leads to a monocyclic structure for the 2,6-isomers of the didehydropyridinium (pyridynium) cation and of didehydropyridine (pyridyne), while SCF and single-reference CCSD computations predict an incorrect bicyclic structure. The IVO-CASCI structures and relative stability for the ground (2)A(1) and excited (2)B(2) states of TDB also accord with the experimentally observed IR spectra and with other highly sophisticated theoretical calculations. The blend of accuracy and reduction in computational cost offered by the present IVO-CASCI analytical gradient method clearly demonstrates that the method provides a practical avenue for studying the geometries of various radicaloid species of different levels of complexity. PMID- 20586460 TI - Chemoselective reductive cross-coupling of 1,5-diene-3-ols with alkynes: a facile entry to stereodefined skipped trienes. AB - A convergent synthesis of highly substituted and stereodefined skipped polyenes is described from the reductive cross-coupling of substituted 1,5-diene-3-ols with alkynes. The control of site selectivity in functionalization of the substituted diene is a central feature of this complex fragment union reaction. PMID- 20586461 TI - Kinetic analysis of his-tagged protein binding to nickel-chelating nanolipoprotein particles. AB - Nanolipoprotein particles (NLPs) are discoidal self-assembling membrane mimetics that have been primarily used as a platform for the solubilization and stabilization of membrane proteins. Nickel-chelating nanolipoprotein particles (NiNLPs) containing nickel-chelating lipids (Ni-lipid) for the targeted immobilization of His-tagged proteins hold promise as carriers of hydrophilic biological molecules for a range of applications. The effect of protein loading (i.e., the number of proteins bound per NiNLP) and Ni-lipid content on the time scales and kinetics of binding are important to various applications such as vaccine development, diagnostic imaging, and drug delivery. We have immobilized hexa-His-tagged LsrB, a Yersinia pestis transport protein, onto NiNLPs to examine the effect of protein binding stoichiometry and Ni-lipid content on the time scales and kinetics of protein binding by surface plasmon resonance (SPR). Data indicate that the dissociation half-time increases with Ni-lipid content up to a molar concentration of 35% and decreases as the number of bound protein per NiNLP increases. These findings indicate that the kinetics of protein binding are highly dependent on both the number of bound protein per NiNLP and Ni-lipid content. PMID- 20586462 TI - Thermodynamic characterization of acacia gum-beta-lactoglobulin complex coacervation. AB - The interactions of beta-lactoglobulin (BLG) with total acacia gum (TAG) in aqueous solutions have been investigated at pH 4.2 and 25 degrees C. Isothermal titration calorimetry (ITC) has been used to determine the type and magnitude of the energies involved in the complexation process of TAG to BLG. Dynamic light scattering (DLS), electrophoretic mobility (mu(E)), turbidity measurements (tau), and optical microscopy were used as complementary methods on the titration mode to better understand the sum of complicated phenomena at the origin of thermodynamic behavior. Two different binding steps were detected. Thermodynamic parameters indicate a first exothermic step with an association constant K(a1) of (48.4 +/- 3.6) x 10(7) M(-1) that appeared to be mostly enthalpy-driven. A positive heat capacity change was obtained corresponding at the signature for electrostatic interactions. The second binding step, 45 times less affinity (K(a2) = (1.1 +/- 0.1) x 10(7) M(-1)), was largely endothermic and more entropy driven with a negative value of heat capacity change, indicative of a hydrophobic contribution to the binding process. The population distribution of the different species in solution and their sizes were determined through DLS. Dispersion turbidity of particles markedly increased and reached a maximum at a 0.015 TAG/BLG molar ratio. Largely more numerous coacervates appeared at this molar ratio (0.015) and two different kinds of morphologies were noticed for the large coacervates. Above the TAG/BLG molar ratio of 0.015, dispersions turbidity decreased, which might be due to an excess of negative charges onto particles as revealed by electrophoretic mobility measurements. The results presented in this study should provide information about the thermodynamic mechanisms of TAG/BLG binding processes and will facilitate the application of the formed supramolecular assemblies as functional ingredients in food and nonfood systems. PMID- 20586463 TI - Crystalline domain structure and cholesterol crystal nucleation in single hydrated DPPC:cholesterol:POPC bilayers. AB - Grazing incidence X-ray diffraction measurements were performed on single hydrated bilayers and monolayers of DPPC:Cholesterol:POPC at varying concentrations. There are substantial differences in the phase and structure behavior of the crystalline domains formed within the bilayers relative to the corresponding monolayers, due to interactions between the opposing leaflets. Depending on the lipid composition, these interactions led to phase separation, changes in molecular tilt angle, or formation of cholesterol crystals. In monolayers, DPPC and cholesterol form a single crystalline phase at all compositions studied. In bilayers, a second crystalline phase appears when cholesterol levels are increased: domains of cholesterol and DPPC form monolayer thick crystals where each of the lipid leaflets diffracts independently, whereas excess cholesterol forms cholesterol bilayer thick crystals at a DPPC:Chol ratio < 46:54 +/- 2 mol %. The nucleation of the cholesterol crystals occurs at concentrations relevant to the actual cell plasma membrane composition. PMID- 20586465 TI - Subtle trade-off existing between (anti)aromaticity, push-pull interaction, keto enol tautomerism, and steric hindrance when defining the electronic properties of conjugated structures. AB - The spatial magnetic properties (through space NMR shieldings, TSNMRS) of conjugated structures (benzenoid/quinonoid keto/enol tautomers, 1,3-dihydroxyaryl 2-aldehydes, Don-pi-Acc chromophores with trade-off existing push-pull vs aromatic behavior) have been calculated by the GIAO perturbation method employing the nucleus independent chemical shift (NICS) concept, and visualized as iso chemical-shielding surfaces (ICSS) of various size and direction. The TSNMRS values, thus obtained, can be successfully employed to quantify and visualize (anti)aromaticity and to identify readily hereby zwitterionic structures due to push-pull behavior of the compounds studied. In addition, the push-pull behavior was quantified by the quotient (pi*/pi) approach of the central partial C=C double bond. PMID- 20586464 TI - Design of single-stranded nucleic acid binding peptides based on nucleocapsid CCHC-box zinc-binding domains. AB - The solution structures of nucleocapsid (NC)-like CCHC zinc-binding domains bound to nucleic acid targets have revealed that these domains bind guanosine residues within single-stranded nucleic acids. Here, we have performed initial studies examining the potential use of NC-like CCHC zinc-binding domains as modules to construct single-stranded nucleic acid binding peptides. The affinity for guanosine-containing single-stranded deoxyribooligonucleotides increases with the number of CCHC domains in the peptide. The length of the linker between domains affects the spacing of guanosine residues in oligonucleotides that are preferentially bound. These studies provide a proof of principle that NC-like CCHC zinc-binding domains can be utilized as a basis for designing peptides that bind specific single-stranded nucleic acid sequences. PMID- 20586466 TI - Microchip electrophoresis of oligosaccharides using large-volume sample stacking with an electroosmotic flow pump in a single channel. AB - The applicability of an online preconcentration technique, large-volume sample stacking with an electroosmotic flow pump (LVSEP), to microchip zone electrophoresis (MCZE) for the analysis of oligosaccharides was investigated. Since the sample stacking and separation proceeded continuously without polarity switching in LVSEP, a single "straight" channel microchip could be employed. In the MCZE analysis of oligosaccharides, sample adsorption onto the channel surface should be suppressed, so the straight microchannel was modified with poly(vinyl alcohol) (PVA). So far, the mechanism of LVSEP in the polymer-coated capillary or microchannel has not been reported, and thus, the LVSEP process in the PVA-coated channel was investigated by fluorescence imaging. Although it is well-known that the PVA coating can suppress the electroosmotic flow (EOF), an enhanced EOF with a mobility of 4.4 x 10(-4) cm(2)/(V x s) was observed in a low ionic strength sample solution. It was revealed that such temporarily enhanced EOF in the sample zone worked as the driving force to remove the sample matrix in LVSEP. To evaluate the analytical performance of LVSEP-MCZE, oligosaccharides were analyzed in the PVA-coated straight channel. As a result, both the glucose ladder and oligosaccharides obtained from bovine ribonuclease B were well enriched and separated with up to 2200-2900-fold sensitivity enhancement compared to those in a conventional MCZE analysis. The run-to-run repeatabilities of the migration time and peak height were good with relative standard deviations of 1.1% and 7.2%, respectively, which were better than those of normal MCZE. By applying the LVSEP technique to MCZE, a complicated voltage program for fluidic control could be simplified from four channels for two steps to two channels for one step. PMID- 20586467 TI - How ambiguous is the local kinetic energy? AB - The local kinetic energy and the closely related local electronic stress tensor are commonly used to elucidate chemical bonding patterns, especially for covalent bonds. We use three different approaches-transformation properties of the stress tensor, quasiprobability distributions, and the virial theorem from density functional theory-to clarify the inherent ambiguity in these quantities, discussing the implications for analyses based on the local kinetic energy and stress tensor. An expansive-but not universal-family of local kinetic energy forms that includes the most common choices and is suitable for both chemical bonding and atoms-in-molecule analysis is derived. A family of local electronic stress tensors is also derived. Several local kinetic energy functions that are mathematically justified, but unlikely to be conceptually useful, are derived. The implications of these forms for atoms-in-molecule analysis are discussed. PMID- 20586468 TI - Structures, stability, vibration entropy and IR spectra of hydrated calcium ion clusters [Ca(H(2)O)(n)](2+) (n = 1-20, 27): a systematic investigation by density functional theory. AB - The low-lying candidates of hydrated calcium ion clusters, [Ca(H(2)O)(n)](2+) with n = 1-20 and 27, have been extensively sought by using density functional theory (DFT) at BLYP/6-311+G(d,p) level. The results showed that the first hydration shell around the calcium ion was fully occupied by six water molecules, whereas the second hydration shell might be fully occupied with different numbers of water molecules. This just corresponds to different growth patterns of the hydrated calcium ion clusters. Furthermore, we revealed that the vibration entropy contributed to the free energy of an isomer significantly. As a result, the stability of some low-lying candidates at zero-temperature was not maintained at finite temperatures. Therefore, we suggested that, at finite temperatures, the realistic products of [Ca(H(2)O)(n)](2+) should be a mixture of the best candidate and some of metastable isomers for a given cluster size. For a cluster having second and/or third shell of water molecules, we found structural transitions between a low-lying structure and the lowest-energy structure undergoing much lower energy barriers. In addition, the IR spectra of the best candidates were predicted, in which the evolution of hydrogen-bond configurations with the cluster size was revealed. PMID- 20586470 TI - New noncentrosymmetric tellurite phosphate material: synthesis, characterization, and calculations of Te2O(PO4)2. AB - A new noncentrosymmetric polar ternary tellurium(IV) oxide phosphate, Te(2)O(PO(4))(2), has been synthesized by a standard solid-state reaction, and the structure was determined by single crystal X-ray diffraction. The material shows a three-dimensional framework structure that is composed of slightly distorted TeO(5) square pyramids and PO(4) tetrahedra. Within the framework three , four-, and seven-membered ring channels are observed along the [100] direction. In addition to structural characterization, second-harmonic generation (SHG) and piezoelectric measurements were performed. Powder SHG measurement on the Te(2)O(PO(4))(2), using 1064 nm radiation, indicated the material has a SHG efficiency of approximately 50 x alpha-SiO(2). Converse piezoelectric measurements revealed a d(33) value of 20 pm V(-1). Thermogravimetric analysis, UV-vis diffuse reflectance, and infrared spectroscopy were also performed, as were electronic structure calculations. Crystal data: Te(2)O(PO(4))(2), monoclinic, space group Cc (No. 9), with a = 5.3819(7) A, b = 13.6990(19) A, c = 9.5866(12) A, V = 686.73(16) A(3), and Z = 4. PMID- 20586469 TI - Silk-elastin-like hydrogel improves the safety of adenovirus-mediated gene directed enzyme-prodrug therapy. AB - Recombinant silk-elastin-like protein polymers (SELPs) are well-known for their highly tunable properties on both the molecular and macroscopic hydrogel levels. One specific structure of these polymers, SELP-815K, has been investigated as an injectable controlled delivery system for the treatment of head and neck cancer via a gene-directed enzyme prodrug therapy (GDEPT) approach. Due to its pore size and gelation properties in vivo, SELP restricts the distribution and controls the release of therapeutic viruses for up to one month. It has been shown that SELP mediated delivery significantly improves therapeutic outcome of the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system in xenograft models of human head and neck cancer. However little is known about potential benefits of this approach with regard to toxicity in the presence of a fully intact immune system. The studies presented here were designed to assess the change in toxicity of the SELP-mediated viral delivery compared to free viral injection in a non-tumor-bearing immune competent mouse model. Toxicity was assessed at 1, 2, 4, and 12 weeks via body weight monitoring, complete blood count (CBC), and blood chemistry. It was found that in the acute and subacute phases (weeks 1-4) there is significant toxicity in groups combining the virus and the prodrug, and matrix-mediated gene delivery with SELP demonstrates a reduction in toxicity from the 2 week time point through the 4 week time point. At the end of the subchronic phase (12 weeks), signs of toxicity had subsided in both groups. Based on these results, recombinant SELPs offer a significant reduction in toxicity of virus-mediated GDEPT treatment compared to free virus injection in the acute and subacute phases. PMID- 20586472 TI - Dissolution and precipitation of clay minerals under geologic CO2 sequestration conditions: CO2-brine-phlogopite interactions. AB - To ensure efficiency and sustainability of geologic CO2 sequestration (GCS), a better understanding of the geochemical reactions at CO2-water-rock interfaces is needed. In this work, both fluid/solid chemistry analysis and interfacial topographic studies were conducted to investigate the dissolution/precipitation on phlogopite (KMg3Si3AlO10(F,OH)2) surfaces under GCS conditions (368 K, 102 atm) in 1 M NaCl. Phlogopite served as a model for clay minerals in potential GCS sites. During the reaction, dissolution of phlogopite was the predominant process. Although the bulk solution was not supersaturated with respect to potential secondary mineral phases, interestingly, nanoscale precipitates formed. Atomic force microcopy (AFM) was utilized to record the evolution of the size, shape, and location of the nanoparticles. Nanoparticles first appeared on the edges of dissolution pits and then relocated to other areas as particles aggregated. Amorphous silica and kaolinite were identified as the secondary mineral phases, and qualitative and quantitative analysis of morphological changes due to phlogopite dissolution and secondary mineral precipitation are presented. The results provide new information on the evolution of morphological changes at CO2-water-clay mineral interfaces and offer implications for understanding alterations in porosity, permeability, and wettability of pre existing rocks in GCS sites. PMID- 20586471 TI - High throughput quantification of N-glycans using one-pot sialic acid modification and matrix assisted laser desorption ionization time-of-flight mass spectrometry. AB - Appropriate glycosylation of recombinant therapeutic glycoproteins has been emphasized in biopharmaceutical industries because the carbohydrate component can affect safety, efficacy, and consistency of the glycoproteins. Reliable quantification methods are essential to ensure consistency of their products with respect to glycosylation, particularly sialylation. Mass spectrometry (MS) has become a popular tool to analyze glycan profiles and structures, showing high resolution and sensitivity with structure identification ability. However, quantification of sialylated glycans using MS is not as reliable because of the different ionization efficiency between neutral and acidic glycans. We report here that amidation in mild acidic conditions can be used to neutralize acidic N glycans still attached to the protein. The resulting amidated N-glycans can then be released from the protein using PNGase F, and labeled with permanent charges on the reducing end to avoid any modification and the formation of metal adducts during MS analysis. The N-glycan modification, digestion, and desalting steps were performed using a single-pot method that can be done in microcentrifuge tubes or 96-well microfilter plates, enabling high throughput glycan analysis. Using this method we were able to perform quantitative MALDI-TOF MS of a recombinant human glycoprotein to determine changes in fucosylation and changes in sialylation that were in very good agreement with a normal phase HPLC oligosaccharide mapping method. PMID- 20586473 TI - Acetylated hyaluronic acid/photosensitizer conjugate for the preparation of nanogels with controllable phototoxicity: synthesis, characterization, autophotoquenching properties, and in vitro phototoxicity against HeLa cells. AB - A proposal is herein examined for a novel yet simple design of a polymeric nanogel, with tumor targeting properties and a controllable phototoxicity, utilizing a low molecular weight-hyaluronic acid (HA(LM))/photosensitizer conjugate. HA(LM) was acetylated prior to being dissolved in DMSO (Ac-HA(LM)) and then was conjugated with different amounts of pheophorbide a (Pba), resulting in the formulation of self-organizing nanogels in aqueous solutions (Ac-HA-Pba 1, 2, and 3). The nanogels observed were below 200 nm in size, with a monodispersed size distribution. The nanogels displayed auto photoquenching qualities in PBS, while their fluorescent intensity strongly correlated with the amount of Pba in the organic solvent (DMSO or DMF). The critical self-quenching concentration (CQC) of the conjugates was found to have decreased as the content of Pba rose. Although Pba was conjugated with HA, the nanogel's photoactivity, in terms of fluorescent properties, singlet oxygen generation, and photocytotoxicity, was approximately maintained. Confocal imaging and FACS analysis showed that Ac-HA Pba nanogels were rapidly internalized into HeLa cells via an HA-induced endocytosis mechanism, a process which could be blocked with the application of an excess of HA polymer. The results of the study indicate that HA-based nanogels can potentially be applied in photodynamic therapy (PDT). PMID- 20586474 TI - Nano building blocks via iodination of [PhSiO1.5]n, forming [p-I-C6H4SiO1.5]n (n = 8, 10, 12), and a new route to high-surface-area, thermally stable, microporous materials via thermal elimination of I2. AB - We describe the synthesis and characterization of the homologous p iodophenylsilsesquioxanes (SQs) [p-I-C(6)H(4)SiO(1.5)](n) (n = 8, 10, 12) via ICl promoted iodination (-40 to -60 degrees C) with overall yields of 80-90% and > 95% para selectivity following recrystallization. Characterization by NMR, FTIR, TGA, and single-crystal X-ray diffraction are reported and compared to data previously published for I(8)OPS. Coincidentally, we report a new synthesis of the elusive pentagonal decaphenyl SQ (dPS) [C(6)H(4)SiO(1.5)](10) and its characterization by NMR and single-crystal X-ray studies. These unique macromolecules possess equivalent chemical functionality but varying symmetries (cubic, pentagonal, and D(2d) dodecahedral), offering the potential to develop homologous series of functionalized star and dendrimer compounds with quite different core geometries and thereby providing the potential to greatly vary structure-property relationships in derivative compounds and nanocomposites made therefrom. We find that all three compounds decompose on heating to approximately 400 degrees C/N(2) with loss of I(2) to form robust, microporous materials with BET surface areas of 500-700 m(2)/g, pore volumes of 0.25-0.31 cm(3)/g, average pore widths of 8 A, and oxidative stabilities > or = 500 degrees C and with solid phase morphologies varying from crystalline to mostly amorphous, as indicated by powder XRD and SEM studies. These latter findings point to important symmetry effects relating directly to packing in the crystalline phase prior to thermolysis. PMID- 20586475 TI - Comparative shotgun proteomics using spectral count data and quasi-likelihood modeling. AB - Shotgun proteomics provides the most powerful analytical platform for global inventory of complex proteomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and allows a global analysis of protein changes. Nevertheless, sampling of complex proteomes by current shotgun proteomics platforms is incomplete, and this contributes to variability in assessment of peptide and protein inventories by spectral counting approaches. Thus, shotgun proteomics data pose challenges in comparing proteomes from different biological states. We developed an analysis strategy using quasi-likelihood Generalized Linear Modeling (GLM), included in a graphical interface software package (QuasiTel) that reads standard output from protein assemblies created by IDPicker, an HTML-based user interface to query shotgun proteomic data sets. This approach was compared to four other statistical analysis strategies: Student t test, Wilcoxon rank test, Fisher's Exact test, and Poisson-based GLM. We analyzed the performance of these tests to identify differences in protein levels based on spectral counts in a shotgun data set in which equimolar amounts of 48 human proteins were spiked at different levels into whole yeast lysates. Both GLM approaches and the Fisher Exact test performed adequately, each with their unique limitations. We subsequently compared the proteomes of normal tonsil epithelium and HNSCC using this approach and identified 86 proteins with differential spectral counts between normal tonsil epithelium and HNSCC. We selected 18 proteins from this comparison for verification of protein levels between the individual normal and tumor tissues using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS). This analysis confirmed the magnitude and direction of the protein expression differences in all 6 proteins for which reliable data could be obtained. Our analysis demonstrates that shotgun proteomic data sets from different tissue phenotypes are sufficiently rich in quantitative information and that statistically significant differences in proteins spectral counts reflect the underlying biology of the samples. PMID- 20586476 TI - Kinetic characterization of Salmonella FliK-FlhB interactions demonstrates complexity of the Type III secretion substrate-specificity switch. AB - The bacterial flagellum is a complex macromolecular machine consisting of more than 20 000 proteins, most of which must be exported from the cell via a dedicated Type III secretion apparatus. At a defined point in flagellar morphogenesis, hook completion is sensed and the apparatus switches substrate specificity type from rod and hook proteins to filament ones. How the switch works is a subject of intense interest. FliK and FlhB play central roles. In the present study, two optical biosensing methods were used to characterize FliK-FlhB interactions using wild-type and two variant FlhBs from mutants with severe flagellar structural defects. Binding was found to be complex with fast and slow association and dissociation components. Surprisingly, wild-type and variant FlhBs had similar kinetic profiles and apparent affinities, which ranged between 1 and 10.5 microM, suggesting that the specificity switch is more complex than presently understood. Other binding experiments provided evidence for a conformational change after binding. Liquid chromatography-mass spectrometry (LC MS) and NMR experiments were performed to identify a cyclic intermediate product whose existence supports the mechanism of autocatalytic cleavage at FlhB residue N269. The present results show that while autocatalytic cleavage is necessary for proper substrate specificity switching, it does not result in an altered interaction with FliK, strongly suggesting the involvement of other proteins in the mechanism. PMID- 20586478 TI - Monomeric and dimeric disulfide complexes of nickel(II). AB - Elemental sulfur reacts with a bulky bis(phosphine)nickel(0) complex to give a monomeric nickel(II) eta(2)-disulfido complex, oxidation of which results in the elimination of sulfur with dimerization to give an eta(2),eta(2) disulfidodinickel(II) derivative in which the S-S bond can be reductively cleaved in a redox-reversible fashion. PMID- 20586477 TI - Development of an enantioselective route toward the Lycopodium alkaloids: total synthesis of lycopodine. AB - Synthesis of a C(15)-desmethyl tricycle core of lycopodine has been accomplished. Key steps in the synthetic sequence include organocatalytic, intramolecular Michael addition of a keto sulfone and a tandem 1,3-sulfonyl shift/Mannich cyclization to construct the tricyclic core ring system. Synthetic work toward this natural product family led to the development of N-(p-dodecylphenylsulfonyl) 2-pyrrolidinecarboxamide, an organocatalyst which facilitates enantioselective, intramolecular Michael additions. A detailed mechanistic discussion is provided for both the intramolecular Michael addition and the sulfone rearrangement. Finally, the application of these discoveries to the enantioselective total synthesis of alkaloid lycopodine is described. PMID- 20586479 TI - Design and synthesis of hierarchical MnO2 nanospheres/carbon nanotubes/conducting polymer ternary composite for high performance electrochemical electrodes. AB - For efficient use of metal oxides, such as MnO(2) and RuO(2), in pseudocapacitors and other electrochemical applications, the poor conductivity of the metal oxide is a major problem. To tackle the problem, we have designed a ternary nanocomposite film composed of metal oxide (MnO(2)), carbon nanotube (CNT), and conducting polymer (CP). Each component in the MnO(2)/CNT/CP film provides unique and critical function to achieve optimized electrochemical properties. The electrochemical performance of the film is evaluated by cyclic voltammetry, and constant-current charge/discharge cycling techniques. Specific capacitance (SC) of the ternary composite electrode can reach 427 F/g. Even at high mass loading and high concentration of MnO(2) (60%), the film still showed SC value as high as 200 F/g. The electrode also exhibited excellent charge/discharge rate and good cycling stability, retaining over 99% of its initial charge after 1000 cycles. The results demonstrated that MnO(2) is effectively utilized with assistance of other components (fFWNTs and poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) in the electrode. Such ternary composite is very promising for the next generation high performance electrochemical supercapacitors. PMID- 20586480 TI - Direct low-temperature nanographene CVD synthesis over a dielectric insulator. AB - Graphene ranks highly as a possible material for future high-speed and flexible electronics. Current fabrication routes, which rely on metal substrates, require post-synthesis transfer of the graphene onto a Si wafer, or in the case of epitaxial growth on SiC, temperatures above 1000 degrees C are required. Both the handling difficulty and high temperatures are not best suited to present day silicon technology. We report a facile chemical vapor deposition approach in which nanographene and few-layer nanographene are directly formed over magnesium oxide and can be achieved at temperatures as low as 325 degrees C. PMID- 20586481 TI - Gadolinium chloride augments tumor-specific imaging of targeted quantum dots in vivo. AB - Nonspecific sequestration of nanoparticles by the reticulo-endothelial system (RES) results in the degradation of image quality of nanoparticle-based imaging. We demonstrate that gadolinium chloride (GdCl3) pretreatment inactivates RES macrophages, thereby increasing circulatory time and amplifying the tumor specific signal of conjugated nanoparticles in vivo. The experimental results were validated using compartmental modeling, and the rate parameters for the observed kinetics pattern were estimated. This pretreatment strategy could have broad applicability across biomedical applications utilizing theranostic nanoparticles that are sequestered by the RES. PMID- 20586482 TI - One-pot synthesis of new substituted 1,2,3,4-tetrahydrocarbazoles via Petasis reaction. AB - The one-pot synthesis of a new substituted 1,2,3,4-tetrahydrocarbazoles has been described via Petasis reactions. These tetrahydrocarbazoles exhibits various medicinal importance and might be suitable for elaboration into larger peptides at carboxy termini. The scope and limitations of this method have been examined. PMID- 20586483 TI - Extensive de novo sequencing of new parvalbumin isoforms using a novel combination of bottom-up proteomics, accurate molecular mass measurement by FTICR MS, and selected MS/MS ion monitoring. AB - Parvalbumins (PRVB) (11.20-11.55 kDa) are considered the major fish allergens. In this work, we propose a novel strategy for extensive characterization of this group of proteins based on the integration of a classical Bottom-Up proteomics approach with accurate Mr determination by FTICR-MS of intact proteins and selected MS/MS ion monitoring (SMIM) of peptide mass gaps. For each PRVB, mass spectra obtained by LC-ESI-IT-MS/MS from two digests (trypsin, Glu-C) were de novo sequenced manually with help of two programs (PEAKS, DeNovoX). The deduced peptide sequences were arranged and the theoretical Mr for the resulting sequences was calculated. Experimental Mr for each PRVB was measured with high mass accuracy by FTICR-MS (0.05-4.47 ppm). The masses of several missing peptide gaps were estimated by comparing the theoretical and experimental Mr, and the MS/MS spectra corresponding to these ions were obtained by LC-ESI-IT-MS/MS in the SMIM scanning mode. Finally, all peptide sequences were combined to generate the final protein sequences. This approach allowed the complete de novo MS-sequencing of 25 new PRVB isoforms. These new sequences belong to 11 different species from the Merlucciidae family, organisms for which genomes remain unsequenced. This study constitutes the report accounting for the higher number of new proteins completely sequenced making use of MS-based techniques only. PMID- 20586484 TI - Cloud-point extraction and delipidation of porcine brain proteins in combination with bottom-up mass spectrometry approaches for proteome analysis. AB - In this study, temperature-induced phase fractionation also known as cloud-point extraction (CPE) with the nonionic surfactant Triton X-114 was used to simultaneously extract hydrophobic and hydrophilic proteins from porcine brain tissue. Various protein precipitation/delipidation procedures were investigated to efficiently remove lipids and detergents while retaining maximum protein recoveries. The best performing delipidation method was then used in combination with CPE to compare three different mass spectrometry (MS) based "bottom-up" proteomic approaches for protein analysis of the porcine brain. In the first approach, the intact proteins were initially separated by one-dimensional (1D) gel electrophoresis. The excised protein bands were digested with trypsin, and the peptides were separated by reversed phase nanoliquid chromatography (RP nanoLC) followed by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis. The other bottom-up proteomic approaches were based on first enzymatical digestion of the proteins followed by RP-nanoLC separation in combination with matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) or on the combination of in-solution isoelectric focusing (IEF) with ESI-nanoLC-MS/MS of the IEF separated peptides. In total, we found and unambiguously identified 331 unique proteins. The overlap between different techniques was about 10%, showing that the use of multiple proteomic approaches is beneficial to yield a better coverage of the proteome. Furthermore, the overlap between the CPE extracted hydrophilic and hydrophobic proteins was rather small (9-16%), indicating an efficient sample preparation technique to extract and separate hydrophilic and hydrophobic proteins from brain tissue. The percentage of identified membrane proteins was 27%, which is in accordance to the fact that about one-third of all genes in various organisms encode for this class of proteins. The results indicate that cloud point extraction is a promising sample preparation tool, which allows simultaneous in depth studies of brain derived membrane proteins as well as hydrophilic proteins. This technique can be very useful when studying human central nervous system (CNS) tissue or animal models of neurological diseases. PMID- 20586485 TI - Research at the intersection of the physical and life sciences. PMID- 20586487 TI - Long-term characterization of indoor and outdoor ultrafine particles at a commercial building. AB - The particle number concentrations in the size range of 10-500 nm were measured inside and outside of a commercial building in Rochester, New York from 2005 to 2009. The indoor ventilation conditions were controlled by a heating, ventilation, and air-conditioning (HVAC) system. The overall average indoor and outdoor particle number concentrations were 2166 cm(-3) and 5214 cm(-3), respectively. Comparison of the indoor and outdoor ultrafine particles (UFP) distributions revealed that indoor sources contributed to the indoor UFP concentrations. The indoor/outdoor (I/O) ratio generally increased with particle size. The I/O ratios in the summer months were higher than those in the winter months. Indoor and outdoor correlations of particle concentrations were slightly weaker in warmer months. These results indicated that changes in the air exchange rates (AER) may have affected the correlation between indoor and outdoor UFP number concentrations. Moreover, indoor activities such as food preparation and cleaning may have contributed to the indoor UFP number concentrations. PMID- 20586488 TI - Surfactant-enhanced desorption and biodegradation of polycyclic aromatic hydrocarbons in contaminated soil. AB - We evaluated two nonionic surfactants, one hydrophobic (Brij 30) and one hydrophilic (C(12)E(8)), for their ability to enhance the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil after it had been treated in an aerobic bioreactor. The effects of each surfactant were evaluated at doses corresponding to equilibrium aqueous-phase concentrations well above the surfactant's critical micelle concentration (CMC), slightly above the CMC, and below the CMC. The concentrations of all 3- and 4-ring PAHs were significantly lower in the soil amended with Brij 30 at the two lower doses compared to controls, whereas removal of only the 3-ring PAHs was significantly enhanced at the highest Brij 30 dose. In contrast, C(12)E(8) did not enhance PAH removal at any dose. In the absence of surfactant, <5% of any PAH desorbed from the soil over an 18 day period. Brij 30 addition at the lowest dose significantly increased the desorption of most PAHs, whereas the addition of C(12)E(8) at the lowest dose actually decreased the desorption of all PAHs. These findings suggest that the effects of the two surfactants on PAH biodegradation could be explained by their effects on PAH bioavailability. Overall, this study demonstrates that the properties of the surfactant and its dose relative to the corresponding aqueous-phase concentration are important factors in designing systems for surfactant-enhanced bioremediation of PAH-contaminated soils in which PAH bioavailability is limited. PMID- 20586489 TI - Validation of a lanthanide tag for the analysis of protein dynamics by paramagnetic NMR spectroscopy. AB - Paramagnetic lanthanide tags potentially can enhance the effects of microsecond to millisecond dynamics in proteins on NMR signals and provide structural information on lowly populated states encoded in the pseudocontact shifts. We have investigated the microsecond to millisecond mobility of a two-point attached lanthanide tag, CLaNP-5, using paramagnetic (1)H CPMG relaxation dispersion methods. CLaNP-5 loaded with Lu(3+), Yb(3+), or Tm(3+) was attached to three sites on the surface of two proteins, pseudoazurin and cytochrome c. The paramagnetic center causes large relaxation dispersion effects for two attachment sites, suggesting that local dynamics of the protein at the attachment site causes mobility of the paramagnetic center. At one site the relaxation dispersions are small and limited to the immediate environment of the tag. It is concluded that paramagnetic relaxation dispersion could represent a sensitive method to probe protein dynamics. However, the selection of a rigid attachment site is of critical importance. PMID- 20586490 TI - Introducing a 2-His-1-Glu nonheme iron center into myoglobin confers nitric oxide reductase activity. AB - A conserved 2-His-1-Glu metal center, as found in natural nonheme iron-containing enzymes, was engineered into sperm whale myoglobin by replacing Leu29 and Phe43 with Glu and His, respectively (swMb L29E, F43H, H64, called Fe(B)Mb(-His)). A high resolution (1.65 A) crystal structure of Cu(II)-CN(-)-Fe(B)Mb(-His) was determined, demonstrating that the unique 2-His-1-Glu metal center was successfully created within swMb. The Fe(B)Mb(-His) can bind Cu, Fe, or Zn ions, with both Cu(I)-Fe(B)Mb(-His) and Fe(II)-Fe(B)Mb(-His) exhibiting nitric oxide reductase (NOR) activities. Cu dependent NOR activity was significantly higher than that of Fe in the same metal binding site. EPR studies showed that the reduction of NO to N(2)O catalyzed by these two enzymes resulted in different intermediates; a five-coordinate heme-NO species was observed for Cu(I)-Fe(B)Mb( His) due to the cleavage of the proximal heme Fe-His bond, while Fe(II)-Fe(B)Mb( His) remained six-coordinate. Therefore, both the metal ligand, Glu29, and the metal itself, Cu or Fe, play crucial roles in NOR activity. This study presents a novel protein model of NOR and provides insights into a newly discovered member of the NOR family, gNOR. PMID- 20586491 TI - Heat-assisted aqueous extraction of rice flour for arsenic speciation analysis. AB - A versatile heat-assisted pretreatment aqueous extraction method for the analysis of arsenic species in rice was developed. Rice flour certified reference materials NIST SRM1568a and NMIJ CRM 7503-a and a flour made from polished rice were used as samples, and HPLC-ICP-MS was employed for the determination of arsenic species. Arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA) were detected in NIST SRM, and As(III), As(V) and DMAA were found in NMIJ CRM and the prepared polished rice flour. The sums of the concentrations of all species in each rice flour sample were 97-102% of the total arsenic concentration in each sample. PMID- 20586492 TI - AAB-sequence living radical chain copolymerization of naturally occurring limonene with maleimide: an end-to-end sequence-regulated copolymer. AB - Sequence control in chain-growth polymerization is still one of the most challenging topics in synthetic polymer chemistry in contrast to natural macromolecules with completely sequence-regulated structures like proteins and DNA. Here, we report the quantitative and highly selective 1:2 sequence-regulated radical copolymerization of naturally occurring (+)-d-limonene (L) and a maleimide (M) in fluoroalcohol giving chiral copolymers with high glass transition temperatures (220-250 degrees C) originating from the specific rigid cyclic structures of the monomers. Furthermore, the combination with a reversible addition-fragmentation chain transfer (RAFT) agent (C-S) via the controlled/living radical polymerization resulted in end-to-end sequence regulated copolymers [C-(M-M-L)(n)-M-S] with both highly sequenced chain ends and main-chain repeating units as well as controlled molecular weights. PMID- 20586494 TI - Electronic and steric control of regioselectivities in Rh(I)-catalyzed (5 + 2) cycloadditions: experiment and theory. AB - The first studies on the regioselectivity of Rh(I)-catalyzed (5 + 2) cycloadditions between vinylcyclopropanes (VCPs) and alkynes have been conducted experimentally and analyzed using density functional theory (DFT). The previously unexplored regiochemical consequences for this catalytic, intermolecular cycloaddition were determined by studying the reactions of several substituted VCPs with a range of unsymmetrical alkynes. Experimental trends were identified, and a predictive model was established. VCPs with terminal substitution on the alkene reacted with high regioselectivity (>20:1), as predicted by a theoretical model in which bulkier alkyne substituents prefer to be distal to the forming C-C bond to avoid steric repulsions. VCPs with substitution at the internal position of the alkene reacted with variable regioselectivity (ranging from >20:1 to a reversed 1:2.3), suggesting a refined model in which electron-withdrawing substituents on the alkyne decrease or reverse sterically controlled selectivity by stabilizing the transition state in which the substituent is proximal to the forming C-C bond. PMID- 20586495 TI - Micropatterned surfaces through moisture-induced phase-separation of polystyrene clay nanocomposite particles. AB - We report micropatterned polystyrene-clay nanocomposite (PCN) surfaces with concavities by moisture-induced phase separation of PCN particles. Micropatterned film with concavity size of 800 nm to 1.3 microm and a high number density of 2 x 10(8) features/cm(2) was obtained by drop-casting PCN solution (20 mg/mL PCN/THF) under ambient relative humidity of 70-80%. It is proposed that water droplets were channeled through the hydrophilic interfaces between the PCN particles, and the two-dimensional array of concavities was formed by spontaneous phase separation due to the presence of rigid clay platelets. The concavity size and number density can be tuned by varying the solvent for PCN. Micropatterned film with concavity size in the range of 650 nm to 1.1 microm with a number density of 5 x 10(7) features/cm(2) was obtained using chloroform as solvent, whereas a concavity size of 150-740 nm and number density of 10(8) features/cm(2) were obtained using carbon disulfide. PMID- 20586493 TI - Design and synthesis of C-2 substituted thiazolo and dihydrothiazolo ring-fused 2 pyridones: pilicides with increased antivirulence activity. AB - Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway in E. coli. Various C-2 substituents were introduced on the pilicide scaffold by design and synthetic method developments. Experimental evaluation showed that proper substitution of this position affected the biological activity of the compound. Aryl substituents resulted in pilicides with significantly increased potencies as measured in pili-dependent biofilm and hemagglutination assays. The structural basis of the PapD chaperone-pilicide interactions was determined by X-ray crystallography. PMID- 20586496 TI - Synthesis of both enantiomers of hemiesters by enantioselective methanolysis of meso cyclic anhydrides catalyzed by alpha-amino acid-derived chiral thioureas. AB - Both ureas and thioureas derived from L- or D-valine act as bifunctional organocatalysts able to induce the enantioselective alcoholysis of mono-, bi-, and tricyclic meso anhydrides. The desymmetrization occurs in near quantitative yields and excellent enantiomeric ratios (up to >99:<1) under low catalyst loading. Both enantiomers of the hemiesters can be directly obtained by changing the configuration of the catalyst. PMID- 20586497 TI - Synthesis of asymmetric peroxides: transition metal (Cu, Fe, Mn, Co) catalyzed peroxidation of beta-dicarbonyl compounds with tert-butyl hydroperoxide. AB - The transition metal (Cu, Fe, Mn, Co) catalyzed peroxidation of beta-dicarbonyl compounds at the alpha position by tert-butyl hydroperoxide was discovered. A selective, experimentally convenient, and gram-scale method was developed for the synthesis of alpha-peroxidated derivatives of beta-diketones, beta-keto esters, and diethyl malonate. Virtually stoichiometric (2-3/1) molar ratios of tert-butyl hydroperoxide and a dicarbonyl compound were used in the reactions with beta diketones and beta-keto esters. The target compounds were synthesized in the highest yields from beta-keto esters (45-90%) and in somewhat lower yields from beta-diketones (46-75%) and malonates (37-67%). PMID- 20586498 TI - Etanercept: an evolving role in psoriasis and psoriatic arthritis. AB - Tumor necrosis factor alpha (TNFalpha) plays a key pathophysiological role in psoriasis and psoriatic arthritis (PsA). Recent interest has thus focused on the clinical potential of TNFalpha antagonists (e.g. etanercept) in these settings. In psoriasis, several large pooled analyses and well-designed clinical trials documented the significant clinical efficacy and generally favorable tolerability of etanercept for up to 96 weeks. Similarly, in PsA, a large phase III trial showed that, etanercept significantly reduced arthritic symptoms and inhibited radiographic disease progression; sustained clinical benefit was again evident for up to 2 years. Etanercept is at the forefront of psoriatic disease management, and continued evolution and evaluation of the compound - for example, in detailed comparative studies and economic analyses - is likely to confirm a key role for etanercept in the treatment of psoriasis and PsA. PMID- 20586499 TI - Psoriasis: targeting therapy towards the inflammatory cascade. AB - Psoriasis is a chronic inflammatory disease of the skin and joints that typically follows a relapsing/remitting disease course. Whereas psoriasis is primarily a T cell-mediated disease, intrinsic alterations in epidermal keratinocytes also play an important role. Tumor necrosis factor alpha (TNFalpha) has been identified as an important cytokine in the inflammatory cascade of psoriasis. The importance of TNFalpha is further underlined by the therapeutic efficacy of compounds that interfere with TNFalpha function, such as biological agents. PMID- 20586500 TI - Managing pediatric patients with psoriasis. AB - Childhood-onset psoriasis affects approximately one-third of the psoriatic population. Among many potential treatments of childhood psoriasis, biological agents are emerging as a valuable option in the management of this disease. In Europe, etanercept has recently been approved for children aged 8 years and over. Data from a well-designed clinical trial indicate that in children, etanercept effectively reduces psoriasis symptoms, with beneficial effects evident as early as 4 weeks after the initiation of treatment. Etanercept is well tolerated; adverse effects are typically mild to moderate in severity. Early data from other biological agents are promising. PMID- 20586501 TI - Psoriatic arthritis: a dermatologist's perspective. AB - Psoriatic arthritis (PsA) is a common, destructive arthritis that may manifest in more than one-third of psoriasis patients. Dermatologists are in a unique position to diagnose PsA early, and to start prompt, effective treatment. Such early intervention with biological agents such as tumor necrosis factor alpha antagonists, which appear to hold particular promise in the long-term management of PsA, may significantly reduce morbidity, improve quality of life and substantially reduce the economic (patient and societal) burden of PsA. PMID- 20586502 TI - Biological agents for chronic wounds. AB - Tumor necrosis factor alpha antagonists (e.g. etanercept) are now being extensively evaluated in the setting of chronic wound healing. Preliminary studies and case reports provide evidence of the clinical potential of these compounds in pyoderma gangrenosum, and further investigations are warranted. A clear rationale also exists for further detailed assessments of the potential efficacy of etanercept in patients with venous leg ulcers or hospital-acquired pressure ulcers. PMID- 20586503 TI - The role of biological agents in the treatment of nail psoriasis. AB - Nail psoriasis affects up to 90% of patients with psoriasis in their lifetime and is seen in 80% of patients with psoriatic arthritis. These changes of nail psoriasis often cause significant pain, psychological effects, and result in restrictions of daily activities. In patients with nail psoriasis, the choice of effective therapy is limited and depends on various factors, including the severity of the disease, the ability of patients to tolerate treatment, and their ability to pay (insurance) for what are, in some cases, expensive treatments. In recent years, biological therapies have proved effective in improving nail psoriasis, have generally proved to be well tolerated and require minimal patient monitoring. In the right situation, therefore, the use of biological agents is justified in patients with psoriatic nail disease. PMID- 20586504 TI - Biological agents for controlling excessive scarring. AB - The potential of various biological agents to reduce or prevent excessive scar formation has now been evaluated in numerous in-vitro studies, experimental animal models and preliminary clinical trials, in some cases with particularly promising results. Perhaps prominent among this group of biological agents, and, to some degree, possibly representing marketed compounds already being used 'off label' to manage excessive scarring, are the tumor necrosis factor alpha antagonist etanercept, and immune-response modifiers such as IFNalpha2b and imiquimod. Additional assessment of these novel agents is now justified with a view to reducing or preventing hypertrophic scars, keloid scars and the recurrence of post-excision keloid lesions. PMID- 20586505 TI - Adverse effects of biological agents in the treatment of psoriasis. AB - Tumour necrosis factor (TNF) antagonists are generally well tolerated, but carry the risk of side effects. In patients with psoriasis, the potential risks with anti-TNF agents may be overestimated because the most commonly reported adverse events are based on studies in patients with rheumatoid arthritis or inflammatory bowel disease. Whereas patients with psoriasis typically receive monotherapy, these patients are treated with biological-based combination therapies. Furthermore, patients with psoriasis have distinctive and different comorbidities, which could play a role in the development of different adverse events. However, the potential risks of the use of biological agents should always be taken into consideration. PMID- 20586506 TI - Etanercept therapy for psoriasis in a patient with active pulmonary tuberculosis. AB - Anti-tumor necrosis factor alpha agents are effective treatments for psoriasis. However, the use of these agents is associated with an increased risk of tuberculosis reactivation. An algorithmic approach to screening for latent tuberculosis infection has been recommended to minimize the risk of tuberculosis reactivation. However, clinical suspicion should override the results of screening tests. This report describes the case of a 49-year-old man who experienced reactivation of latent tuberculosis during treatment with etanercept, despite a negative tuberculin skin test and chest radiograph showing no abnormalities before the commencement of etanercept therapy; this patient was able to receive further treatment with etanercept following treatment for tuberculosis. PMID- 20586507 TI - A case of severe psoriasis with an apparent incomplete response to anti-tumour necrosis factor alpha treatment. AB - This report covers a case of severe psoriasis that appeared to respond well to treatment with subcutaneous etanercept, with good recovery of the arthropathic component. However, there were distinct areas at the patient's hands and wrists that failed to respond to such treatment. A standard series of patch tests yielded strong positive responses to the vaseline ointment and mercaptobenzothiazole mix, substances that the patient had constantly applied, twice daily, before and during the anti-tumour necrosis factor alpha therapy course, as an emollient, rubber-gloved topical treatment. This case is reported to provide further evidence of the efficacy of etanercept treatment, and to confirm that the immunopathological pathway leading to psoriasis and allergic contact dermatitis (ACD) sometimes goes into 'overdrive' in ACD, giving a mixed pattern, involving each of the branches of the immune system. PMID- 20586508 TI - Beneficial neurological effects observed in a patient with psoriasis treated with etanercept. AB - A 53-year-old woman with a history of psoriasis presented with severe cutaneous lesions associated with psoriasis. The woman was mentally handicapped; she was able to converse monosyllabically with her mother only and was very limited in social interactions. After preliminary investigations, a biological treatment was proposed. Etanercept was started in October 2006. The patient responded rapidly and, after 3 months, achieved a 75% improvement in the psoriasis area and severity index (PASI 75) score. Most notable, however, was that she began interacting with other people, even if they were not familiar to her. Subsequent cutaneous relapses were treated successfully with etanercept. Very few articles regarding etanercept and neurological or psychiatric problems are present in the literature. According to recent studies, etanercept could improve verbal fluency and cognitive and behavioural functions in Alzheimer's disease, so that we can suggest a potential role and use in neurological disorders. PMID- 20586509 TI - A patient with psoriasis and vitiligo treated with etanercept. AB - Psoriasis is a chronic, immune-mediated, inflammatory dermatosis whose aetiopathogenesis remains unclear, although tumour necrosis factor alpha (TNFalpha) appears to play a crucial role. The biological potential of TNFalpha inhibitors, such as etanercept, which reduce the inflammatory cascade, has radically changed the therapeutic management of patients with psoriasis and other immunomediated inflammatory diseases, associated with TNFalpha. The pathogenesis of the selective destruction of melanocytes in vitiligo is not fully understood, although there is growing evidence that several T helper type 1 cytokines, particularly TNFalpha, may be involved in the depigmentation process. A patient is described who presented with both psoriasis and vitiligo, and was treated with etanercept. After 24 weeks of therapy, the patient's psoriasis had improved markedly and the patient noted a mild improvement of vitiligo, with a reduction in macules and repigmentation in the scapular region. PMID- 20586510 TI - Etanercept therapy for psoriasis in a patient with numerous comorbidities. AB - A recent study demonstrated an association between psoriasis and dilated cardiomyopathy. Tumour necrosis factor alpha (TNFalpha) may be involved in the pathogenesis of dilated cardiomyopathy and therefore, anti-TNFalpha agents may play a role in the treatment of dilated cardiomyopathy. The case of a 51-year-old woman with severe psoriasis and numerous comorbidities including dilated cardiomyopathy is described. During treatment with etanercept, the patient's psoriasis improved rapidly without any worsening of her other conditions. Etanercept was safe and effective in the treatment of severe psoriasis in a patient with numerous comorbidities, including dilated cardiomyopathy. PMID- 20586511 TI - Nicolau syndrome following etanercept administration. AB - Nicolau syndrome (NS), or embolia cutis medicamentosa, is a well-known but rare adverse effect of a still largely unidentified pathogenesis, observed primarily after the intramuscular administration of various drugs. NS is characterized by immediate excruciating pain, early pallor and erythema and oedema at the injection site, followed by cutaneous, subcutaneous and even muscular aseptic necrosis in a livedoid pattern. It is a potentially serious reaction that is little influenced by which drug is injected. A case is reported of NS following a subcutaneous self-injection of etanercept for psoriasis and psoriatic arthritis. This case is remarkable because NS developed after subcutaneous and not after intramuscular drug administration, and because no cases of NS following the injection of tumour necrosis factor alpha inhibitors have been reported in the literature or in the World Health Organization adverse drug reactions database. Although not directly linked to the drug, the occurrence of NS has to be considered in patients receiving biological agents. PMID- 20586512 TI - A case of dystrophic epidermolysis bullosa improved with etanercept for concomitant psoriatic arthritis. AB - Epidermolysis bullosa is a group of inherited, chronic, non-inflammatory skin disorders, and dystrophic epidermolysis bullosa (DEB) is one of the most severe variants. The role of tumour necrosis factor alpha (TNFalpha) has not been reported in the pathogenesis of DEB. A DEB case is reported that appears to have responded well to the TNFalpha inhibitor etanercept given for the treatment of concomitant psoriatic arthritis. A progressive improvement in DEB was apparent over the first 3 months of treatment and persistent good control of DEB was noted over 3 years of therapy. A correlation between DEB improvement and etanercept has not been made, but the case may provide insight into the causal mechanisms of DEB. PMID- 20586513 TI - Onset of lichen planus during treatment with etanercept. AB - The case is presented of a 24-year-old Caucasian man with moderate to severe psoriasis vulgaris resistant to traditional topical and systemic treatments who developed lichen planus (LP) during treatment with etanercept. Etanercept was effective, but LP developed after 8 months' therapy. Although LP was deemed possibly related to etanercept therapy, the treatment was not discontinued and topical corticosteroids were applied with some clinical improvement. This is the second report of LP associated with etanercept treatment. PMID- 20586514 TI - Etanercept in a patient with severe psoriasis and latent viral hepatic disease and latent tuberculosis. AB - This case report describes the effective use of etanercept in a 63-year-old male patient with moderate to severe psoriasis and vitiligo unresponsive to local and systemic therapies. Latent tuberculosis was diagnosed at baseline and the patient was treated with isoniazid for 9 months. One month after starting isoniazid, etanercept therapy (12 weeks) for psoriasis was initiated. One month later, hepatitis B virus (HBV) markers were detected, but virological tests for active HBV were negative. Isoniazid and etanercept treatments were completed without incidence. Further clinical investigations are required to confirm the potential effects of anti-tumour necrosis factor alpha agents in such patients. PMID- 20586515 TI - Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active controlled phase III study. AB - BACKGROUND: Tapentadol is a novel, centrally acting analgesic with mu-opioid receptor agonist and norepinephrine reuptake inhibitor activity. OBJECTIVE: to evaluate the efficacy and safety of Tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain. METHODS: this was a randomized, double blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received Tapentadol ER, oxycodone CR or placebo for a 3 week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive Tapentadol ER 100-250 mg twice daily, oxycodone HCl CR 20-50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation. RESULTS: efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], -0.7 [-1.04, 0.33]), and throughout the maintenance period (-0.7 [-1.00, -0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], -0.3 [-0.67, -0.00]) but not at week 12 (-0.3 [-0.68, 0.02]). A significantly higher percentage of patients achieved > or =50% improvement in pain intensity in the Tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved > or =50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, Tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342). CONCLUSION: treatment with Tapentadol ER 100-250 mg twice daily or oxycodone HCl CR 20-50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with Tapentadol ER than with oxycodone CR. PMID- 20586516 TI - Treating psoriasis with etanercept in italian clinical practice: prescribing practices and duration of remission following discontinuation. AB - BACKGROUND: conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. OBJECTIVE: to assess the use of etanercept for psoriasis in clinical practice in Italy. METHODS: this was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score >or=10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction >or=50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached >or=10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction >or=75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to re-treatment was evaluated. Use of other antipsoriatic medications was recorded throughout. RESULTS: eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (-71.5%) and mean BSA involvement (-79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). CONCLUSION: in clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life. PMID- 20586517 TI - Cost Effectiveness of Paricalcitol versus a non-selective vitamin D receptor activator for secondary hyperparathyroidism in the UK: a chronic kidney disease markov model. AB - BACKGROUND: secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Non-selective vitamin D receptor (VDR) activator treatment has been used to treat the condition but is ineffective for many patients with hypercalcaemia and hyperphosphataemia and may precipitate worsening of their condition. Compared with non-selective VDR activator treatment, use of the VDR ligand paricalcitol may increase survival and reduce the risk of morbidities in patients with SHPT, which may have health economic consequences. OBJECTIVE: the objective of this study was to determine the cost effectiveness of paricalcitol versus a non selective VDR activator for the treatment of SHPT in patients with CKD in the UK setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official UK price/tariff lists and national population statistics. The comparator was alfacalcidol, a non-selective VDR activator medication. The primary perspective of the study was that of the UK National Health Service (NHS). The efficacy outcomes (reductions in SHPT, proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. The year of costing for costs determined in the study was 2006. RESULTS: the reference case analysis was a 10-year time horizon, based on a comparison of paricalcitol with a non-selective VDR activator, which is started in CKD stage 3 (moderate reduction in glomerular filtration rate [GFR] with kidney damage) and continued in CKD stage 4 (severe reduction in GFR) and CKD stage 5 (established kidney failure). The use of paricalcitol leads to an additional medical cost of pound3224 ($US5970). The health benefits of paricalcitol lead to an increase in LYG of 0.52 and a gain in QALYs of 0.465. Therefore the use of paricalcitol results in an incremental cost-effectiveness ratio of pound6933/QALY ($US12 840/QALY) from the primary perspective of the NHS. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: this model showed that the favourable clinical benefit of paricalcitol results in positive short- and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early CKD may be cost effective from the UK NHS perspective versus non selective VDR activator medication. PMID- 20586518 TI - Proton pump inhibitor-induced neutropenia: possible cross-reactivity between omeprazole and pantoprazole. AB - Proton pump inhibitors (PPIs) are widely used drugs in the treatment or prophylaxis of peptic ulcer and gastro-oesophageal reflux disease. In addition to their well documented efficacy, these drugs are generally well tolerated with only rare serious adverse effects having been reported. Neutropenia and agranulocytosis are rare adverse events associated with PPI treatment. All previously published cases of isolated neutropenia have involved omeprazole, but leukopenia is labelled as a possible adverse effect in the summary of product characteristics of the other PPIs. In this report, we describe a case of omeprazole-induced neutropenia with further recurrence upon pantoprazole treatment. A 60-year-old man with chronic alcoholism and a medical history of pulmonary tuberculosis, untreated chronic C hepatitis, peripheral artery disease, chronic obstructive pulmonary disease and stable stage 3 chronic kidney disease was admitted with dehydration and malnutrition. Omeprazole 20 mg/day and sucralfate 3 g/day were started for diffuse gastritis on gastric endoscopy. While the patient's blood cell count had been within the normal range before this treatment, routine laboratory examination revealed moderate neutropenia (0.9 x 109/L) after 9 days of treatment. His blood cell count returned to the normal range after discontinuation of omeprazole and no further episodes of neutropenia were noted in the following months. One year later, oesophago-gastroscopy revealed a hiatal hernia with an extensive zone of Barrett's oesophagus. As the lesions did not improve with ranitidine and sucralfate therapy, the patient was started on pantoprazole 40 mg/day. His initial white blood cell count was normal, but moderate neutropenia (0.8 x 109/L) was again noted after only 2 days of pantoprazole treatment. Complete and further stable normalization was obtained within 3 days after replacement of pantoprazole with ranitidine. Toxic and immune mediated mechanisms are the two commonly proposed mechanisms to explain the pathogenesis of drug-induced neutropenia. This report suggests that PPI-induced neutropenia is immune mediated and argues for a possible cross-reactivity between the two PPIs, as has already been described for PPI-induced hypersensitivity reactions. The report also indicates that patients with a history of neutropenia induced by one PPI may be at risk of recurrence of neutropenia if given another member of this drug class. In these patients, close haematological monitoring is proposed. PMID- 20586519 TI - Optimizing the management of fibromyalgia. Introduction. PMID- 20586520 TI - Financial and clinical characteristics of fibromyalgia: a case-control comparison. AB - OBJECTIVE: To compare healthcare utilization and costs between subjects with and without fibromyalgia (FM) using claims data from a large health benefits company in the United States. STUDY DESIGN: Retrospective cohort. METHODS: We analyzed 24 months of medical and pharmacy claims data comparing healthcare utilization and costs among Humana members diagnosed with FM to a propensity score matched control group without a diagnosis for FM. FM cases were identified as members aged 18 years and older, with at least 2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification codes 729.0 and/or 729.1. The first medical claim for FM was utilized as the index date. RESULTS: A total of 9988 FM cases and 9988 controls were included in the analysis. Compared with controls, the use of pain-related medications by FM cases was approximately 2 times higher with opioids being used most commonly. FM cases utilized a mean (SD) of 22.5 (23.9) and 31.1 (26.6) outpatient services per year in the prediagnosis and postdiagnosis periods, respectively, compared with 14.8 (20.5) and 16.3 (24.5) among controls (P <.01). Office visits, tests, and procedures represented the majority of utilization. During the postdiagnosis period, the mean per-patient per-month costs for outpatient services among FM cases was $377 ($760) and $217 ($740.87) among controls (P <.01). CONCLUSION: FM cases had significantly higher utilization and costs compared with controls. Office visits, tests and procedures, and the use of pain-related medications accounted for the largest absolute differences between the 2 groups. PMID- 20586521 TI - Patterns of healthcare utilization and cost in patients with newly diagnosed fibromyalgia. AB - OBJECTIVES: To compare healthcare utilization and costs in the year preceding and following initial diagnosis of fibromyalgia (FM). METHODS: Using a large US health insurance claims database, we identified all persons with newly diagnosed FM (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 729.1) between January 1, 2003, and December 31, 2005 ("FM patients"). Each patient's first-noted claim with a diagnosis of FM was designated the "index date," and all pharmacy, outpatient, and inpatient claims were compiled over the 12-month periods preceding and following this date ("prediagnosis" and "postdiagnosis," respectively). Patients with incomplete pre- or postdiagnosis data were excluded. Healthcare utilization and costs were compared between the 2 periods. RESULTS: A total of 1803 patients met all study inclusion criteria; mean (SD) age was 50.4 (9.4) years; 91% were women. Comorbidities were common, including arthritis (21% of study subjects), back pain (20%), and painful neuropathic disorders (16%). The percentage of study subjects receiving various pain-related medications increased from pre- to postdiagnosis, including opioids (51.3% vs 55.9%), antiepileptics (22.6% vs 28.6%), and tricyclic antidepressants (15.5% vs 21.2%) (all P <.01). Mean total healthcare costs also increased by $1725 between these periods (mean [95% confidence interval]: $9324 [$8655, $10,092] vs $11,049 [$10,245, $11,973], respectively; P <.01). CONCLUSIONS: Patients with FM are often seen for other medical problems prior to initial diagnosis. Levels of healthcare utilization and costs are high during both the pre- and postdiagnosis periods. PMID- 20586522 TI - Pregabalin: an alpha2-delta (alpha2-delta) ligand for the management of fibromyalgia. AB - OBJECTIVE: To review the efficacy and safety of pregabalin, an alpha(2)-delta (alpha(2)-delta) ligand, for the management of fibromyalgia (FM). METHODS: Review of 2 pivotal phase 3 trials that evaluated the efficacy and safety of pregabalin for the management of FM. RESULTS: FM is a chronic condition that is characterized by widespread musculoskeletal pain and has a greater prevalence in women than in men. In a 14-week, randomized, double-blind trial, pregabalin at all 3 doses (300, 450, and 600 mg daily) resulted in significantly greater improvements in pain and function relative to placebo. Parallel with these improvements, greater proportions of patients in the pregabalin groups reported improvement in global disease status compared with placebo. In a second study designed to evaluate the durability of response, patients were randomized to up to 6 months of treatment with pregabalin or placebo after a 6-week, open-label, dose-optimization treatment phase. Based on predefined criteria for loss of therapeutic response, patients treated with pregabalin were observed to maintain a therapeutic response for a significantly longer duration than patients treated with placebo. Pregabalin was tolerated by most patients in both trials; the incidence of the most commonly reported adverse events (dizziness, somnolence, weight gain, headache, dry mouth) appeared to be dose-related. CONCLUSION: Pregabalin has been demonstrated to be efficacious and well-tolerated for the management of FM. PMID- 20586523 TI - Initial use of pregabalin, patterns of pain-related pharmacotherapy, and healthcare resource use among older patients with fibromyalgia. AB - OBJECTIVE: To characterize the comorbidities, pain-related pharmacotherapy, and healthcare resource use among older patients with fibromyalgia (FM) newly prescribed pregabalin in clinical practice. METHODS: Using the PharMetrics database, patients with FM aged 65 or more years (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) who were newly prescribed pregabalin (index event) on or after July 1, 2007, were identified (N = 98, mean age 72.4 +/- 6.4 years; 81.6% female). Prevalence of comorbidities, pharmacotherapy, and healthcare resource use/costs (pharmacy, outpatient, inpatient, total) were examined during the 6-month preindex and postindex periods. RESULTS: Patients had a variety of comorbidities including various disorders generally associated with an older population, such as hypertension (41.8%), diabetes (22.5%), and coronary artery disease (15.3%). On average, patients received 3.3 +/- 2.3 pregabalin prescriptions; the average number of days of therapy was 121 +/- 88.9. Patients had a high medication burden in both the pre- and postindex periods; opioids were the most commonly prescribed medications (54.1% vs 59.2%); combination therapy was also common, with opioids and antidepressants the most frequent (35% in both periods). Except for the use of selective serotonin reuptake inhibitors, which decreased significantly in the postindex period (24.5% vs 19.4%, P = .0253), there were no changes in use of any of the other medications, including nonsteroidal anti-inflammatory drugs (36.7% vs 32.7%), tramadol (17.4% vs 24.5%), muscle relaxants (18.4% vs 21.4%), tricyclic antidepressants (21.4% vs 18.4%), serotonin and norepinephrine reuptake inhibitors (10.2% vs 12.2%), and anticonvulsants (17.4% vs 21.4%) after initiation of pregabalin therapy. There were decreases in the number of physician office visits and total outpatient visits (both P <.01) and in the proportion of patients with visits to physical therapists (21.4% vs 12.2%, P = .0201); however, there were no changes in healthcare costs (pharmacy, outpatient, inpatient, or total) from the pre- to postindex period. CONCLUSIONS: These results suggest a substantial medication and comorbidity burden in older patients with FM. Although it is not possible to establish cause-and-effect relationships in claims database studies, results also suggest that the initiation of pregabalin was cost-neutral. Further evaluation is warranted to characterize FM and determine appropriate management strategies in this fragile population. PMID- 20586524 TI - Impact of a prior authorization for pregabalin on health plan drug expenditures. AB - OBJECTIVE: The objective of this study is to examine the financial impact of a prior authorization (PA) intervention for pregabalin in a commercially insured US population via an economic model. METHODS: An Excel-based model was developed to simulate 2 hypothetical scenarios for health plans: one with a PA on pregabalin, and another without a PA. In the PA scenario, a variable percentage of pregabalin prescriptions were assumed to be approved and dispensed, the remainder being denied or a substitute product dispensed (branded or generic alternatives). In the "no PA" scenario, all pregabalin prescriptions were assumed to be filled. The market shares of these products, including pregabalin, were based on secondary prescription data. The model calculated the total drug acquisition cost and cost of PA administration in each scenario for a cohort of 1000 patients over a 1-year period. Patients switching to pregabalin following denial were accounted for in the model. Sensitivity analyses were carried out varying the PA approval rates and prescription share of pregabalin and limiting the range of substituted products. RESULTS: The pregabalin prescribing rate was set to 10.3% in both the PA and "no PA" scenarios, with a denial rate of 50% in the PA scenario, consistent with the IMS prescription volume. The calculated drug acquisition cost for the PA scenario was $885,564 compared with $888,822 for the "no PA" scenario, a difference of 0.4%, after factoring in the cost of PA administration. The calculated PA administration cost was $4121. Eliminating the PA administration cost results in a cost for the PA scenario of $881,443, 0.8% below the "no PA" scenario. Lowering the pregabalin PA approval rate from 50% to 10% decreased the costs of the PA scenario to $879,660, 1.0% lower than the "no PA" scenario. Raising the pregabalin market share to 20% in the "no PA" scenario increased the costs of that scenario to $902,714, 1.9% higher than the PA scenario. Limiting the substituted products for denied pregabalin prescriptions in the PA scenario to the 2 most common products, valproate sodium and gabapentin (both generics), lowered the cost of the PA scenario to $875.412, 1.5% below the "no PA" scenario cost. With half of the denied pregabalin patients switching to pregabalin during the course of the year, the cost of the PA scenario increased to $892,550, 0.4% higher than the "no PA" scenario. CONCLUSION: Potential savings due to PA protocols on pregabalin are low, in the 1% to 2% range across a variety of scenarios, because of the relatively low pregabalin market share (about 10%) in typical health plans and the absence of a significant difference in cost for the most commonly substituted products. Patients who switch to pregabalin after an initial denial will further reduce savings to health plans. PMID- 20586525 TI - The influence of biological, social, and developmental factors on language acquisition in pre-term born children. AB - The objective of this study is to evaluate language outcome in pre-term children, considering multiple factors. The hypothesis is that early communicative capacity (pre-verbal communicative utterances) is affected mainly by biological (prematurity, birth weight, and gender) and social factors (maternal education), while more advanced linguistic abilities (i.e., combinatorial and syntactic abilities) are mostly influenced by previously acquired communicative abilities. Eighteen monolingual Italian pre-term children (birth weight between 750 and 1600 grams, gestational age <37 weeks; 13 males and five females) were compared with a control group of 18 age-matched full-term children (8 males, 10 females). The longitudinal design comprised motor and cognitive assessment at 14 and 36 months, and communicative evaluation by direct observation at 14, 24, 30, and 36 months, and by indirect observation at 24 and 30 months. The main results evidenced were delayed development in pre-term compared to full-term children, particularly after 24 months of age; intra-individual differences in the pre-term group; and a strong effect of prematurity on communicative ability at 14 and 24 months; however, more advanced communicative developmental stages were influenced both by prematurity and by previously acquired linguistic skills. PMID- 20586526 TI - Bidirectional interference between speech and postural stability in individuals with Parkinson's disease. AB - Because people frequently talk while engaged in other activities, and because Parkinson's disease (PD) is known to diminish multi-tasking performance, this study examined dual task interference between speaking and postural stability in nine individuals with PD, seven age-matched, and 10 healthy young controls. Participants repeated a target utterance and performed a rise to toes task in both single and dual task conditions. Diphthong transitions were measured from audio recordings and postural variables reflecting planning, coordination, and stability were derived from a multi-camera motion capture system and force plate recordings. Thus, sensitive measures of both speech and postural control were obtained. The group with PD performed more poorly than both control groups for the isolated postural task, but their single task speech measures did not differ from the controls, in spite of listener ratings which indicated mild-to-moderate dysarthria severity. The group with PD showed evidence of bidirectional dual task interference in that there were reduced diphthong extents and slopes along with smaller, slower, and less stable postural movements. These results indicate that concurrent performance of speech and a challenging postural control task impairs speech and postural stability in persons with PD and may result in greater risk during daily activities. PMID- 20586527 TI - Speech motor program maintenance, but not switching, is enhanced by left hemispheric deep brain stimulation in Parkinson's disease. AB - Speech reaction time (SRT) was measured in a response priming protocol in 12 participants with Parkinson's disease (PD) and hypokinetic dysarthria "on" and "off" left-hemispheric deep brain stimulation (DBS). Speech preparation was measured during speech motor programming in two randomly ordered speech conditions: speech maintenance and switching. Double blind testing was completed in participants with DBS of globus pallidus pars interna (GPi) (n = 5) or subthalamic nucleus (STN) (n = 7). SRT was significantly faster in the maintenance vs switch task, regardless of DBS state. SRT was faster in the speech maintenance task "on" stimulation, while there was no difference in speech switching "on" and "off" DBS. These data suggest that left-hemispheric DBS may have differential effects on aspects of speech preparation in PD. It is hypothesized that speech maintenance improvements may result from DBS-induced cortical enhancements, while the lack of difference in switching may be related to inhibition deficits mediated by the right-hemisphere. Alternatively, DBS may have little influence on the higher level motor processes (i.e., motor planning) which it is believed the switch task engaged to a greater extent than the maintenance task. PMID- 20586528 TI - Kinematic analysis of lingual function in dysarthric speakers with Parkinson's disease: An electromagnetic articulograph study. AB - Dysarthria in people with Parkinson's disease (PD) has been widely studied. However, a limited number of studies have investigated lingual function during speech production in this population. This study aimed to investigate lingual kinematics during speech production using electromagnetic articulography (AG-200 EMA). The PD group consisted of eight dysarthric speakers with PD and was matched with a group of eight controls. The tongue tip and tongue back movements of all participants during sentence production were recorded by EMA. Results showed that, perceptually, the participants with PD were mildly dysarthric. Kinematic results documented comparable (for alveolar sentence production) and increased (for velar sentence production) range of lingual movement in the PD group when compared to the control group. Lingual movement velocity, acceleration, and deceleration were also increased in the PD group, predominantly for the release phase of consonant production during sentence utterances. The PD group had longer duration in the production of alveolar consonant and comparable duration in the production of velar consonant. The results of the present study suggest the presence of impaired lingual control in individuals with PD. Increased range of articulatory movement, primarily in the release phase of consonant production, may account for articulatory imprecision in this population. PMID- 20586529 TI - Fatigue management by speech-language pathologists for adults with traumatic brain injury. AB - This study uses a qualitative approach to examine common techniques used by speech-language pathologists (SLPs) to manage fatigue in communication intervention following traumatic brain injury (TBI). Thirteen SLPs from New Zealand hospital and rehabilitation services completed semi-structured interviews in which they discussed their current management strategies. A number of management-related themes recurred throughout the interviews, highlighting the basis of fatigue-management-focused (FMF) communication intervention. The four fatigue-related themes were: intervention structure, client and family strategies, monitoring by both the client and therapist, and lifestyle and daily activities. From these four themes, a model of current SLP practice was developed for clients with TBI. This model will provide the basis for future studies evaluating the effectiveness of FMF communication intervention. PMID- 20586530 TI - Emergent literacy profiles of preschool-age children with specific language impairment. AB - The primary aim of the present study was to explore the heterogeneity of emergent literacy skills among preschool-age children with specific language impairment (SLI) through examination of profiles of performance. Fifty-nine children with SLI were assessed on a battery of emergent literacy skills (i.e., alphabet knowledge, print concepts, emergent writing, rhyme awareness) and oral language skills (i.e., receptive/expressive vocabulary and grammar). Cluster analysis techniques identified three emergent literacy profiles: (1) Highest Emergent Literacy, Strength in Alphabet Knowledge; (2) Average Emergent Literacy, Strength in Print Concepts; and (3) Lowest Emergent Literacy across Skills. After taking into account the contribution of child age, receptive and expressive language skills made a small contribution to the prediction of profile membership. The present findings, which may be characterized as exploratory given the relatively modest sample size, suggest that preschool-age children with SLI display substantial individual differences with regard to their emergent literacy skills and that these differences cannot be fully determined by children's age or oral language performance. Replication of the present findings with a larger sample of children is needed. PMID- 20586531 TI - The catechol-O-methyl-transferase gene in tardive dyskinesia. AB - Tardive dyskinesia (TD) is a severe and potentially irreversible motor side effect linked to long-term antipsychotic exposure. Changes in dopamine neurotransmission have been implicated in the etiology of TD, and catechol-O methyl-transferase (COMT) is an enzyme that metabolizes dopamine. OBJECTIVES: We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD. METHODS: We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans). RESULTS: We found a significant association between the marker rs165599 in the 3' untranslated region of COMT and TD (AA versus G carrier: OR(AA)=2.22, 95% CI:1.23-4.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n=6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (OR(ValVal)=1.63, 95% CI: 1.09-2.45; P=0.019) but not in males. CONCLUSIONS: Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed. PMID- 20586532 TI - The safety and tolerability of clozapine in aged patients: a retrospective clinical file review. AB - OBJECTIVES: A clinical file review was conducted of clozapine use in three aged psychiatry services in Melbourne, Australia, to compare its safety and tolerability with findings reported in the literature. METHODS: The review period spanned the intervals from 2008 to the services' origins between 11 and 15 years earlier. The files of all patients treated with clozapine during this period were checked with respect to adverse effects and the reasons for ceasing treatment. RESULTS: Clozapine was prescribed to 75 patients (mean age 74.2 years, range 65 89) with doses ranging from 25-800 mg daily (mean 296 mg). Treatment was stopped within the review period in 37 (49%) cases. Reasons for discontinuation included death (n=14), non-fatal adverse events (n=12), patient choice (n=8) and other factors (n=3). While none of the 14 deaths could be linked directly to treatment, orthostatic hypotension might have contributed to a single fatal cerebrovascular accident. There were three cases of "red alert" leukopenia, none of which progressed to agranulocytosis. In general, side effects were more frequent than in a previous report concerning aged patients, most probably because clozapine doses were higher. CONCLUSIONS; Most of the adverse events leading to treatment cessation occurred within the first month, emphasising the need for slow titration. Strict monitoring procedures ensured that there were no fatal haematological adverse events. PMID- 20586533 TI - Clinical correlates of low serum carnitine levels in hospitalized psychiatric patients. AB - OBJECTIVE: We sought to evaluate clinical correlates of low serum carnitine levels in hospitalized psychiatric patients. METHODS: We retrospectively reviewed the charts of 40 psychiatric inpatients identified to have low serum carnitine levels. RESULTS: Cognitive impairment was present in 38 (95%) cases, frequently accompanied by imbalance, agitation and extrapyramidal symptoms. Valproate therapy was encountered in 28 (70%) patients. The dosage of valproate negatively correlated with total and free carnitine levels (P = 0.003 and 0.0136). Polypharmacy also affected carnitine levels, indicating additional modulatory effects on carnitine metabolism. We encountered a disproportionately high prevalence of mental retardation and dementia in association with hypocarnitinemia. CONCLUSION: We hypothesize that in the context of mental illness hypocarnitinemia may be associated with metabolic encephalopathy and cognitive impairment. As carnitine deficiency is a potentially treatable condition further studies are warranted. PMID- 20586534 TI - Altered auditory processing in patients with panic disorder: a pilot study. AB - OBJECTIVES: Clinical and electrophysiological studies suggest that panic disorder (PD) patients show disturbed response inhibition to sensory stimuli. Thus, habituation of neuronal activation after repeated sine tone stimulation was assessed by functional magnetic resonance imaging (fMRI) in patients with PD. METHODS: Twenty patients with PD and 20 age- and gender-matched healthy controls were assessed by 3T fMRI for auditory habituation. During three stimulation cycles of digitally generated pulsed (nu=5 Hz) 800-Hz sine tones alternating with silent periods, activation of the auditory cortex and other anxiety- or sensory integration-related regions was assessed. Brain activation was further analyzed dependent on functional serotonin transporter (5-HTT) gene variation (5-HTTLPR). RESULTS: PD patients demonstrated an extended brain activity in the first stimulation block, which normalized during the second stimulation cycle. A positive correlation with anxiety measures (HAMA) and an increased activity of distinct anxiety- or sensory integration-related areas (e.g., BA 22, BA 10) were seen during the third block of auditory stimulation. There was a significant interaction of left amygdala activation and the 5-HTTLPR S allele. CONCLUSIONS: Our results support the hypothesis of an aberrant processing of sensory information in PD patients. This phenomenon may underlie an enhanced responsiveness to anxiety-relevant or irrelevant stimuli possibly increasing PD vulnerability. PMID- 20586535 TI - Serotonergic neurotransmission in early Parkinson's disease: a pilot study to assess implications for depression in this disorder. AB - OBJECTIVES: Depression, a disease usually accompanied by a serotonergic deficit, has been observed in about 40% of patients suffering from Parkinson's disease (PD). Thus, a serotonergic dysfunction in PD can be assumed. We aimed to investigate the interaction between serotonergic (5-HT) and dopaminergic activity in early PD. We hypothesized a serotonergic as well as a dopaminergic deficit in PD patients. We also assumed a correlation between these neurotransmitters indicating a relationship between dopaminergic and serotonergic function in PD. METHODS: Nine unmedicated PD patients before and 12 weeks after L-dopa treatment and nine healthy subjects were examined using the loudness dependence of auditory evoked potentials (LDAEP), a promising indicator of central serotonergic function. Dopaminergic transporters (DAT) were collected using (123)I-FP-CIT and single photon emission computer tomography (SPECT). LDAEP values were correlated with (123)I-FP-CIT SPECT data. RESULTS: A significant difference between LDAEP of controls and patients (P= 0.05) suggested lower serotonergic activity in PD. Twelve weeks after initiation of L-dopa treatment this difference was lost between patients and controls (P= 0.20). There was a trend towards a correlation between LDAEP and DAT (r= 0.65; P = 0.057) of the unmedicated patients, suggesting a low serotonergic activity may be related to a dopamine deficit in PD. CONCLUSIONS: Our results support the hypothesis that serotonergic neurotransmission is decreased in untreated PD and suggest that a low serotonergic activity may be related to the dopamine pathology in PD. This could be related to the high prevalence of depression in PD. PMID- 20586536 TI - Impact of portal vein embolization on expression of cancer stem cell markers in regenerated liver and colorectal liver metastases. AB - OBJECTIVE: Little is known about the expression of stem cell markers in normal liver and colorectal liver metastases (CLM). The aim of this paper is to assess whether patterns of stem cell marker expression differ between normal liver tissue and CLM and to determine whether a clinical model of liver regeneration induced by portal vein embolization (PVE) has any influence on these patterns of expression in both regenerated liver tissue and cancer. MATERIALS AND METHODS: Immunohistochemistry was used to provide semi-quantitative analysis of patterns of expression in tissue samples of liver and tumor tissue pre- and post-PVE in 23 patients with CLM. CD133, CD44 and Oct4 were studied. RESULTS: There was no expression of CD133, CD44 or Oct4 in normal liver tissue before PVE but there was high expression of CD133 and CD44 in CLM. PVE had no significant influence on stem cell marker expression either in regenerated liver tissue or in tumor when compared with pre-PVE samples. CONCLUSION: Liver regeneration following PVE does not seem to involve stem cells. Stem cell marker expression by CLM supports the stem cell theory of carcinogenesis which is not influenced by PVE. PMID- 20586537 TI - Does sleep dysfunction affect anorectal motility in healthy adults? PMID- 20586538 TI - Detection of unrecognized clinical heart failure in elderly hypertensive women attended in primary care setting. AB - OBJECTIVE: To determine the proportion and clinical features of unrecognized heart failure (HF) in hypertensive women >=65 years attended in Spain. METHODS: A cross-sectional study carried out in primary healthcare setting. Patients were considered to present unrecognized clinical diagnosis of HF if they had not been previously diagnosed but fulfilled Framingham criteria for HF diagnosis. RESULTS: Of 3500 patients, the proportion of unrecognized clinical HF was 26.3%. In comparison with women without HF, all cardiovascular risk factors were more prevalent in patients with unrecognized HF; the same was observed for target organ damage, being the most frequent left ventricular hypertrophy (LVH) (54.1% vs 15.5%, p<0.0001), and for the presence of cardiovascular disease, being the most common coronary heart disease (24.8% vs 9.8%, p<0.0001). Predictive factors associated with the presence of unrecognized HF were LVH (OR =4.84) and the presence of previous cardiovascular disease (OR =2.26) Blood pressure control was worse in patients with unrecognized HF (16.6% vs 33.9%, p <0.01). CONCLUSIONS: More than a quarter of hypertensive women >=65 years may have clinical data of unrecognized HF. Hypertensive women with unrecognized clinical HF have a worse clinical profile and worse BP control rates than those without HF. PMID- 20586540 TI - Preferential tumour accumulation of gold nanoparticles, visualised by Magnetic Resonance Imaging: radiosensitisation studies in vivo and in vitro. AB - PURPOSE: To investigate the radiosensitisation of gold nanoparticles (GNP) with an average diameter of 5 nm coated with the gadolinium chelating agent dithiolated diethylenetriaminepentaacetic gadolinium (Au@DTDTPA:Gd) in vitro and in mice bearing tumours (MC7-L1). MATERIALS AND METHODS: In vivo, the gadolinium chelate coating allows one to perform real-time Magnetic Resonance Imaging (MRI) pharmacokinetic analysis during intravenous infusion. Experiments were performed following treatment with 10 Gy of 150 kVp X-rays. In vitro experiments were also performed with clonogenic assays to generate dose response curves for the same cells. RESULTS: We observed a preferential accumulation of Au@DTDTPA:Gd in tumours; a substantial toxicity for tumour cells in vitro, but no obvious toxicity for mice; and the absence of a synergistic effect with Au@DTDTPA:Gd and radiation in all experiments. CONCLUSIONS: The additional absorption of radiation and the subsequent increase in secondary electrons, attributable to the presence of gold in Au@DTDTPA:Gd, does not lead to radiosensitisation. However, this chelating agent exhibits a chemotherapeutic action which warrants further investigation. When compared to positive results obtained by others on radiosensitisation by GNP, the present study suggests that the chemotherapeutic and radiosensitising properties of GNP may depend strongly on the nature of the coating. PMID- 20586539 TI - Use of proton-pump inhibitors and their associated risks among frail elderly nursing home residents. AB - OBJECTIVE: The aim of this study is to investigate the use of proton-pump inhibitors (PPI) and their associated risks among frail elderly nursing home residents. DESIGN: A cross-sectional study. SETTING: General practice. SUBJECTS: An assessment of residents (n = 1987, mean age 83.7 years) in all nursing homes in Helsinki was carried out in February 2003. Data included demographic characteristics, symptoms such as diarrhea, vomiting and constipation, use of various drugs, and medical diagnoses. OUTCOME: Coded data analysis with NCSS statistical program. Multivariate logistic regression analysis served to determine which variables were independently associated with diarrhea; variables which were statistically significant or near p < 0.05 in univariate analyses were included. RESULTS: Altogether 433 residents were on PPIs. The factors associated with regular PPI use in univariate analyses included poor functional status, higher number of comorbidities, higher number of medications and lactose intolerance. The users had suffered from a prior ventricular or duodenal ulcer, cancer and coronary heart disease more often than the non-users. In accordance with our hypothesis, the users of PPIs more often had diarrhea (19.7%) than the non-users (12.9%) (p < 0.001), and they had a prior hip fracture (28.5%) more often than the non-users (19.4%) (p < 0.001). In logistic regression analysis the use of PPIs had an independent association with diarrhea (OR 1.60 (95% CI 1.20 to 2.15). CONCLUSION: Physicians should avoid unnecessary long-term use of PPIs, particularly among frail elderly long-term care patients. PMID- 20586541 TI - Activation of adenosine A(3) receptors supports hematopoiesis-stimulating effects of granulocyte colony-stimulating factor in sublethally irradiated mice. AB - PURPOSE: Research areas of 'post-exposure treatment' and 'cytokines and growth factors' have top priority among studies aimed at radiological nuclear threat countermeasures. The experiments were aimed at testing the ability of N(6)-(3 iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), an adenosine A(3) receptor agonist, to modulate hematopoiesis in sublethally irradiated mice, when administered alone or in a combination with granulocyte colony-stimulating factor (G-CSF) in a two-day post-irradiation treatment regimen. MATERIALS AND METHODS: A complete analysis of hematopoiesis including determination of numbers of bone marrow hematopoietic progenitor and precursor cells, as well as of numbers of peripheral blood cells, was performed. The outcomes of the treatment were assessed at days 3 to 22 after irradiation. RESULTS: IB-MECA alone has been found to induce a significant elevation of numbers of bone marrow granulocyte macrophage progenitor cells (GM-CFC) and peripheral blood neutrophils. IB-MECA given concomitantly with G-CSF increased significantly bone marrow GM-CFC and erythroid progenitor cells (BFU-E) in comparison with the controls and with animals administered each of the drugs alone. CONCLUSIONS: The findings suggest the ability of IB-MECA to stimulate hematopoiesis and to support the hematopoiesis-stimulating effects of G-CSF in sublethally irradiated mice. PMID- 20586542 TI - Response of pancreatic cancer cells treated with interferon-alpha or beta and co exposed to ionising radiation. AB - PURPOSE: Clinical trials on pancreatic cancer demonstrated that interferons (IFN) improve the therapeutic index of combined radio- and chemotherapy. This is believed to be due to radiosensitisation of cells, which, however, needs experimental verification. MATERIALS AND METHODS: Here, we compared the survival response of ten pancreatic tumour cell lines following ionising radiation (IR), interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and combined treatment. The effect of combination treatment on apoptosis induction was also determined. RESULTS: In most cell lines IFN treatment on its own exerted cytotoxicity, which was independent of the expression level of the IFN receptor on the cell surface. Three cell lines showed a radiosensitisation effect while two showed radioprotection. Although IFN-alpha is commonly used in the clinic, IFN-beta induced a stronger cytotoxic response than IFN-alpha in vitro. The likely mechanism of enhancement of radiosensitivity in the responsive cell lines was shown to be an increase of the radiation-induced apoptotic response by IFN pretreatment. CONCLUSIONS: Given that the in vitro data do not conform to the impressive clinical results observed after combined radio- and chemotherapy with IFN-alpha, it is reasonable to conclude that the sensitising effect of IFN is not mediated through modulating the intrinsic radiosensitivity of pancreatic cancer cells. PMID- 20586543 TI - Oxidative stress induces mainly human centrin 2 polymerisation. AB - PURPOSE: To determine the human centrin 2 (Hscen 2) protein response to oxidising radicals in vitro and to evaluate the consequences on its biological functions. MATERIALS AND METHODS: Hscen 2 was submitted to hydroxyl and azide radicals produced by radiolysis in the absence of oxygen. The resulting products were characterised by biochemical, spectroscopic and mass spectrometry techniques. Their thermodynamics parameters of complexation with C-terminal fragment of Xeroderma pigmentosum C protein (C-XPC), one of the Hscen 2 cellular partners, were quantified by isothermal titration calorimetry (ITC). RESULTS: Both hydroxyl and azide radicals induce centrin 2 polymerisation as we characterised several intermolecular cross-links generating dimers, trimers, tetramers and higher molecular mass species. These cross-links result from the formation of a covalent bond between the only tyrosine residue (Tyr 172) located in the C-terminal region of each monomer. Remarkably, dimerisation occurs for doses as low as a few grays. Moreover, this Hscen2 dimer has a lower affinity and stoechiometry binding to C XPC. CONCLUSIONS: These results show that as oxidative radicals induce high proportions of irreversible damages (polymerisation) centrin 2 is highly sensitive to ionising radiation. This could have important consequences on its biological functions. PMID- 20586544 TI - Examining the validity of Poissonian models against the birth and death TCP model for various radiotherapy fractionation schemes. AB - PURPOSE: To compare the results obtained for tumour control probability (TCP) in protracted treatments, we used two models which apply Poisson statistics for clonogenic cell distribution and a non-Poissonian model, emphasising the conditions for the validity of Poissonian models. Previously published results on two cell lines growing as megacolonies in vitro irradiated with conventional and accelerated dose fractionation schemes were used. MATERIALS AND METHODS: The expressions of TCP for three models are described and conclusions are drawn on the applicability of each model, and their usefulness for different fractionations. RESULTS: The fits to experimental data are shown and the parameter values for both Poissonian and non-Poissonian models are given. We also determined if differences exist in repopulation rate and other related parameters, for different protocols of treatment. CONCLUSIONS: Both the Poissonian models, when they satisfied the required conditions, and the non Poissonian model, gave acceptable fits. We observed no significant differences in repopulation for different irradiation protocols. PMID- 20586545 TI - A multicenter, case-control study on risk factors for antepartum stillbirth. AB - OBJECTIVE: As the influence of socio-demographic variables, lifestyle and medical conditions on the epidemiology of stillbirth (SB) is modified by population features, we aimed at investigating the role played by these factors on the incidence of SB in a developed country. STUDY DESIGN: Multivariate logistic regression analysis (OR with 95% CI) was utilized in a prospective multicentre nested case-control study to compare in a 1:2 ratio stillborn of >22 weeks gestation with matched for gestational age live-born (LB) infants. Intrapartum SB were excluded. RESULTS: Two hundred fifty-four consecutive SBs and 497 LBs were enrolled. Socio-demographic variables were equally distributed. Fetal malformations (7.96, 2.69-23.55), severe intrauterine growth restriction (IUGR) (birthweight <= 5(th) %ile) (4.32, 2.27?8.24), BMI > 25 (2.87, 1.90-4.33), and preeclampsia (PE, 0.40, 0.21-0.77) were recognized as independent predictors for SB. At term, only BMI > 25 was associated with SB (7.70, 2.9-20.5). CONCLUSION: Fetal malformations, severe IUGR and maternal BMI > 25 were associated with a significant increase in the risk of SB; PE presented instead a protective role. Maternal BMI > 25 was the only risk factor for SB identified in term pregnancies. PMID- 20586546 TI - Inflammatory and infectious risk factors are associated with the response to tocolysis in patients with preterm labor. AB - OBJECTIVE: Inflammation/infection is the most frequent conditions leading to preterm delivery (PTD). A few studies have assessed the clinical efficacy of long term tocolysis with ritodrine hydrochloride. In this study, the relationship among inflammatory/infective risk factors of PTD, the response to long-term tocolysis, and timing of delivery were evaluated in women with preterm labor. METHODS: On the basis of different responses to long-term tocolysis, defined as >= 7 days tocolysis, the cohort were classified as: (i) patients delivering at term (Group A) and (ii) patients delivering preterm (group B). Group B was subclassified as: (i) delivery before 48 h (group B1); (ii) delivery between 48 h and 7 days (Group B2), and (iii) delivery after 7 days (Group B3). Group B is divided in early preterm (<32 weeks) (Group B early) and late PTD (32-36 weeks) (Group B late). RESULTS: Group A delivered at term and Group B preterm. Group B showed significantly higher (p < 0.0001) rate of CRP, bacterial vaginosis, and chorioamnionitis at placental histological examination than Group A. The same parameters were statistically higher (p < 0.0001) in group B1 than in B3. CRP, chorioamnionitis at placental histological examination was statistically higher (p < 0.0001) in Group B early than in Group B late. CONCLUSIONS: This retrospective study suggested that in women affected by preterm labor, the long term tocolysis with intravenous ritodrine is able to prolong gestation beyond 7 days, in absence of inflammatory/infective risk factors of PTD. PMID- 20586547 TI - Plasma visfatin level in women with polycystic ovary syndrome. AB - OBJECTIVE: The aim of this study is to compare the serum level of visfatin between patients with polycystic ovary syndrome (PCOS) and control subjects matched for age and body mass index (BMI) and to assess the possible correlations of visfatin to the hormonal and metabolic parameters of the syndrome. MATERIAL AND METHOD: Fifty-five patients with PCOS diagnosis composed of 25 obese, 13 overweight, 17 normal weight subjects and 49 women without concomitant disease matched for age and BMI were included in this study. RESULTS: Serum visfatin levels were similar in normal weight PCOS and control group. Visfatin levels in obese and overweight patients with PCOS were higher than that found in control women with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR. Obese women with PCOS had also significantly higher visfatin levels than normal weight women with PCOS. CONCLUSION: Visfatin levels in obese and overweight patients with PCOS were higher than that found in females without concomitant disease with similar BMI, and visfatin had positive linear correlation with BMI, waist circumference and HOMA-IR. PMID- 20586548 TI - Haemostatic and cytokine changes in gestational diabetes mellitus. AB - BACKGROUND: Limited data indicate the existence of a hypercoagulable state and the possible involvement of pro-inflammatory cytokines in the pathogenesis of gestational diabetes mellitus (GDM). AIM: To characterise the coagulation inhibitor and cytokine profiles in women with GDM. METHODS: Two groups of women in the third trimester of pregnancy were studied: GDM (n = 150) and controls: women with normal pregnancy (n = 100); GDM in their first post-delivery day (n = 52). LABORATORY ASSAYS: Plasma fibrinogen, antithrombin (AT), protein C, total and free protein S, interleukins-2, 6 and 8 (IL-2, 6, 8). RESULTS: During pregnancy, the only significant alterations noted were higher levels of body mass index, fibrinogen and total protein S in women with GDM when compared to normal pregnancy. In the post-delivery group, there was further elevation in the levels of plasma fibrinogen and significant drop in the level of total protein S, protein C and AT. Significant elevation of IL-2 and IL-6 levels was recorded only in post-delivery group. CONCLUSION: In GDM, the only indicator of a tendency towards hypercoagulability is the higher fibrinogen levels as compared to normal pregnancy. This feature along with the higher body mass index and presumed associated insulin resistance suggests that GDM may be a mild form of the metabolic syndrome. The lack of significant change in the levels of pro inflammatory cytokines do not support the existence of an inflammatory state in GDM. PMID- 20586549 TI - Sertoli-Leydig cell tumour in a 13-year-old girl. AB - Sertoli-Leydig cell tumours account for less than 0.2% of ovarian malignancies. We describe the case of a Sertoli-Leydig cell tumour in a 13-year-old girl who presented with symptoms of hyperandrogenism. We give an overview over current literature and discuss options of therapy of rare Sertoli-Leydig cell tumours. PMID- 20586550 TI - Tibolone in postmenopausal women: a review based on recent randomised controlled clinical trials. AB - AIM: To critically discuss the use of tibolone (T), in light of a series of very recent double-blind placebo (PL) controlled trials (LISA, LIFT, OPAL, THEBES, LIBERATE) conducted worldwide in a large number of postmenopausal women (PMW). METHODS: The most relevant publications on T therapy in PMW were considered with emphasis on menopausal symptoms, quality of life, sexuality, bone, cardiovascular system (CVS) and oncologic risk. RESULTS: T significantly relieves climacteric symptoms and improves mood and sexual well-being (LISA). T is as effective as estrogen-progestin therapy in preventing bone loss and reducing the relative risk of vertebral and non-vertebral fractures (LIFT). By using surrogate endpoints of the individual risks for the CVS, studies show mixed results, but a favourable effect on acute miocardial infarction and thromboembolism has been documented (THEBES, LIFT, OPAL). Although findings about endometrial and colon cancer are reassuring, conclusive data on breast cancer risk with T are not available and an increased risk of recurrence in women with previous breast cancer emerged (LIBERATE). CONCLUSIONS: T is effective in treating menopausal syndrome with a good tolerability profile. In spite of some unsolved issues in term of safety, T is still a good treatment option for early PMW. PMID- 20586551 TI - Clinical, ultrasonographic, computed tomography and histopathological manifestations of ovarian steroid cell tumour, not otherwise specified: our experience of a rare case with female virilisation and review of the literature. AB - INTRODUCTION: Ovarian steroid cell tumours, not otherwise specified (NOS) are rare sex cord-stromal tumours of the ovary. These tumours should be considered a cause of isosexual precocious puberty in children and virilisation in adults. CASE: We report a case of 40-year-old woman with mental handicap who presented with 3 years of amenorrhea and progressive virilisation. Pelvic ultrasonography identified a 6.19 * 6.15 cm well-defined echogenic-multilobular mass arising from the left ovary. Fluid in the cul-de-sac was noted. Colour Doppler examination with endovaginal ultrasonography showed high vascularity of the tumour with low resistance to flow. A computed tomography (CT) scan of the upper and lower abdomen showed a lobular mass with diaphragms in the left adnexal structure and fluid in the cul-de-sac; no adrenal gland enlargement or additional tumour was detected. Laboratory analysis revealed increased levels of serum total testosterone. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histological examination showed a benign steroid cell tumour, NOS without evidence of necrosis, haemorrhage or invasion. The immunohistochemical study showed that the tumour cells were positive for inhibin, CD 99, Melan A and vimentin and negative to CK AE1, CK AE3, progesterone and estrogen receptors. CONCLUSION: Careful medical history, physical examination, laboratory serum values and imaging studies are helpful in making the pre-operative diagnosis. Steroid cell tumours, NOS are usually benign, unilateral and characterised by the composition of two similar-appearing polygonal cell types. They differ from Leydig cell tumours in the lack of crystals of Reinke in their cytoplasm. PMID- 20586552 TI - Electron emission and product analysis of estrone: progesterone interactions studied by experiments in vitro. AB - Recent studies showed that hormones like progesterone, testosterone, etc. can eject [Formula: see text] (solvated electrons). By means of electron transfer processes via the brain, the hormones communicate with other biological systems in the organism. The present study proves that also estrone is able to emit electrons. Their yield strongly depends on the concentration of the hormone, temperature and on the absorbed energy. The metabolites resulting from this process are likewise able to generate electrons, however with much smaller yields. The formation of the estrone metabolites is studied by HPLC-analyses. In vitro experiments with MCF-7 cells demonstrate the distinct effect of progesterone on the carcinogenity of estrone metabolites. Probable reaction mechanisms for explanation of the observed effects are postulated. PMID- 20586553 TI - Polymorphisms in ESR1, ESR2 and HSD17B1 genes are associated with fertility status in endometriosis. AB - OBJECTIVE: To investigate whether polymorphisms in genes involved in biosynthesis and signalling of sex steroids influence susceptibility to endometriosis and to infertility associated with it. MATERIALS AND METHODS: Patients with endometriosis (n = 150) and fertile controls (n = 199) were genotyped for polymorphisms in oestrogen receptor genes ESR1 (rs2234693 - T/C single nucleotide polymorphism (SNP), dinucleotide (TA)(n) repeat) and ESR2 (dinucleotide (CA)(n) repeat), progesterone receptor gene PGR (rs10895068 - G/A SNP, 306-bp Alu insertion), 17beta-hydroxysteroid dehydrogenase type 1 gene HSD17B1 (rs605059 - A/G SNP), and aromatase gene CYP19A1 (rs10046 - C/T SNP, (TTTA)(n) tetranucleotide repeat, 3-bp TCT insertion/deletion polymorphism). RESULTS: The HSD17B1 A/G SNP A allele increased overall endometriosis risk and the risk of stage I-II disease, while ESR1 longer (TA)(n) repeats only correlated with susceptibility to stage I-II endometriosis. When considering patients' fertility status, HSD17B1 A/G SNP A allele and ESR1 longer (TA)(n) repeats were associated with endometriosis accompanied by infertility, while ESR2 shorter (CA)(n) repeats were linked with endometriosis without infertility. Other polymorphisms were distributed similarly among patients and controls. CONCLUSIONS: Genetic variants in ESR1, ESR2, and HSD17B1 genes could modify susceptibility to endometriosis and might influence the fertility status in endometriosis patients. PMID- 20586554 TI - Placental hormones and identification of pregnancy at risk. PMID- 20586555 TI - Reliability and validity of a new ankle electrogoniometer. AB - OBJECTIVES: To establish reliability, accuracy and concurrent validity of a new electrogoniometer (SG110A, Biometrics) for measuring ankle movement. METHODS: The new electrogoniometer, placed at the lateral malleolus (A-perp), was compared to a customary electrogoniometer (SG110, Biometrics), placed along the Achilles tendon (A-para). Concurrent recordings were made with motion analysis. Common dance movements were performed by 17 dancers on two days. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were calculated for sagittal angular displacements. RESULTS: Instrument and intra-tester reliability of A-perp was high (r >or= 0.985, r >or= 0.979, respectively). Criterion and concurrent validity were also high (r >or= 0.954, r >or= 0.937). SEM ranged from 1.43 degrees to 6.99 degrees. CONCLUSIONS: The high ICC values establish acceptable reliability and validity. Subjects found A-perp more comfortable. Although both electrogoniometers are acceptable (comparable SEM) to measure extreme ankle motions, the greater comfort and durability of the new A-perp sensor is advantageous. PMID- 20586556 TI - A psychosomatic intervention in pregnant in-patient women with prenatal somatic risks. AB - PURPOSE: This study examined whether a short-term psychosomatic intervention during pregnancy had effects on characteristics of labour and delivery as well as on the long-term course of anxiety, depression and physical complaints in pregnant in-patient women. METHODS: All gynaecological and obstetric inpatients of a university hospital, who had either exhibited complications during their pregnancy or were considered high-risk pregnancies, were examined. Symptoms of anxiety and depression (HADS) and physical symptoms (GBB) were assessed by standardised questionnaires. Women with elevated scores on either the HADS or the GBB were randomly assigned to either a treatment group, which had received a psychosomatic intervention or an untreated control group. Of the n = 238 women who were assessed during their stay in our hospital, n = 135 were included in the follow-up 1-year later. RESULTS: More than one-third of the participants (38.7%) had elevated scores of anxiety, depression and/or physical symptoms. The psychosomatic intervention had a significant effect on anxiety scores (p = 0.006), but not on depression scores, physical complaints and characteristics of labour and delivery. CONCLUSIONS: Findings suggest that a short-term psychosomatic intervention can have a positive long-term effect on anxiety symptoms. Future studies are needed to show whether the reduction of anxiety symptoms in turn can lead to a reduction of postnatal complications and lower rates of disturbed mother-child interactions. PMID- 20586557 TI - Perinatal transmission of hepatitis B virus: could hospitals be doing more? PMID- 20586558 TI - Immunomodulators: use in combined therapy against leishmaniasis. PMID- 20586560 TI - Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections. AB - Use of nonsystemic antimicrobials with activity against enteropathogens is a promising approach for treatment of infectious diarrhea and other nonsystemic gastrointestinal infections. Rifaximin is approved by the US FDA for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients aged 12 years and older, and for the reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients aged 18 years or older. Rifaximin has been available in Italy since 1987 and overall is approved in 33 countries for various conditions, such as acute and chronic infections, bacterial diarrhea, HE, and pre- and postsurgical prophylaxis. There is accumulating evidence on the benefit of rifaximin for nonsystemic gastrointestinal infections. This article will serve as an update on rifaximin. The pharmacology and pharmacodynamics of rifaximin along with an updated review on the bacterial susceptibility to rifaximin will be presented. Finally, clinical trials with rifaximin for nonsystemic gastrointestinal indications will be updated. PMID- 20586561 TI - Fighting antibiotic resistance all over Europe. AB - On 10-13 April 2010, the 20th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) took place in Vienna, Austria. The scientific program touched a wide range of issues, some controversial, in the fields of clinical microbiology and infectious diseases. Particular attention was dedicated to modern aspects in research methodology, the European Committee on Antimicrobial Susceptibility Testing breakpoints and methods, infection control programs, antibiotic stewardship and new therapeutic challenges for antibiotic resistant bacteria. This year ECCMID attracted more than 7000 delegates from 98 countries all over Europe and beyond. The participation of a such significant number of scientists presented a unique opportunity for discussion on several clinical and research topics. PMID- 20586562 TI - Inappropriate antimicrobial use and potential solutions: a Middle Eastern perspective. AB - Addressing the many challenges posed by escalating antimicrobial resistance requires a strategy at institutional, community, national, regional and international levels. Partners in the development of such a strategy should include representatives from clinical and veterinary medicine, public health, microbiology, animal husbandry, the pharmaceutical and agriculture industries as well as behavioral sciences. In the Middle East, antimicrobial resistance is a crisis at the present time. It stems from a wide range of problems; however, there are few studies from this region about factors associated with proliferating resistance. In this article, we explore inappropriate antimicrobial use in this part of the world and suggest possible solutions to mitigate the problem. PMID- 20586563 TI - Fastidious intracellular bacteria as causal agents of community-acquired pneumonia. AB - Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis. PMID- 20586564 TI - Prevention of ventilator-associated pneumonia. AB - Ventilator-associated pneumonia (VAP) is an important source of morbidity and mortality in critically ill patients. Many interventions are touted to prevent VAP but studies supporting these interventions are difficult to interpret owing to an exceedingly poor correlation between clinical diagnosis of VAP and the presence of an invasive pneumonia. There is consequently a risk that purported decreases in VAP rates may reflect decreases in oropharyngeal colonization rates more than reductions in invasive disease. To circumvent this source of error, it is critical to assess the impact of intervention measures on patient outcomes rather than on VAP rates alone. This article will review selected VAP prevention methods using this framework and advocate for the development of a new surveillance definition that will more reliably predict patient outcomes. PMID- 20586566 TI - Current management of bloodstream infections. AB - Bloodstream infection (BSI) is a frequent complication of invasive infections. The presence of bacteremia has therapeutic and prognostic implications. Here we review recent changes in the epidemiology, diagnosis and treatment of BSI (excluding candidemia). The evidence of the impact of healthcare-association in many community-onset episodes and the increase in drug-resistant pathogens causing BSI in the community and hospitals is reviewed. The emergence of molecular methods as an alternative tool for the diagnosis of BSI and novel aspects of clinical management, particularly of some multidrug-resistant organisms. Several quality indicators related to the diagnosis and management of bacteremia in hospitals are proposed. PMID- 20586567 TI - Contemporary management of cardiovascular implantable electronic device infections. AB - Cardiovascular implantable electronic device (CIED) implantation rate has substantially risen in the foregoing decades. Unfortunately, this upsurge in CIED implantation rate has been accompanied by a disproportionate rise in the rate of CIED infections. Device infection is a major complication of CIED implantation, necessitating removal of an infected device followed by systemic antimicrobial therapy and reimplantation of a new system. In this article, we review the current epidemiology, risk factors, diagnostic strategy and contemporary management of CIED infection. In addition, we address the vexing question of how to best manage patients with Staphylococcus aureus bacteremia, in the setting of an implanted device, but no overt clinical signs of CIED infection. Lastly, we discuss the preventive strategies to minimize risk of CIED infection. PMID- 20586565 TI - New drugs and regimens for treatment of TB. AB - Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug resistant organisms. PMID- 20586568 TI - Dengue fever: diagnosis and treatment. AB - Dengue fever is a common tropical infection. This acute febrile illness can be a deadly infection in cases of severe manifestation, causing dengue hemorrhagic shock. In this brief article, I will summarize and discuss the diagnosis and treatment of this disease. For diagnosis of dengue, most tropical doctors make use of presumptive diagnosis; however, the definite diagnosis should be based on immunodiagnosis or viral study. Focusing on treatment, symptomatic and supportive treatment is the main therapeutic approach. The role of antiviral drugs in the treatment of dengue fever has been limited, but is currently widely studied. PMID- 20586570 TI - Fomepizole for the treatment of pediatric ethylene and diethylene glycol, butoxyethanol, and methanol poisonings. AB - INTRODUCTION: The use and clinical efficacy of the alcohol dehydrogenase inhibitor fomepizole is well established for the treatment of ethylene glycol and methanol poisonings in adults. METHODS: A computerized search of the U.S. National Academy of medicine and EMBase databases was undertaken to identify published cases of patients treated with fomepizole. This search strategy identified 14 published cases related to the topic of this review: 10 due to ethylene glycol poisoning, 1 due to diethylene glycol poisoning, 1 due to butoxyethanol ingestion, and 2 due to methanol poisoning. The median age of these cases was 5.5 years old. FOMEPIZOLE IN GLYCOL AND GLYCOL ETHER POISONING: For the 10 ethylene glycol poisoned patients, the median recorded values of their arterial pH was 7.27 (range 7.03-7.38), serum bicarbonate concentration was 13 mEq/L (range 2-25), and ethylene glycol concentration was 2,140 mg/L (range 130 3,840). Eight of these patients were not hemodialyzed. The eight patients who were not hemodialyzed had ethylene glycol concentrations as high as 3,500 mg/L and serum bicarbonate concentrations as low as 4 mEq/L. All 10 patients had resolution of their metabolic acidosis and recovered without sequelae. The half times of ethylene glycol elimination ranged from 9 to 15 h during fomepizole therapy, which is faster than the 19.7 h reported in adults. The two patients who ingested diethylene glycol or butoxyethanol all recovered without sequelae. The patient who ingested the butoxyethanol had a serum bicarbonate concentration of 13 mEq/L and was not hemodialyzed. FOMEPIZOLE IN METHANOL POISONING: One of the two children who ingested methanol was hemodialyzed. Both cases had a similar degree of severity. DOES FOMEPIZOLE OBVIATE THE NEED FOR HEMODIALYSIS?: Based on the experience reviewed herein it appears that, as in adults, hemodialysis may not be necessary in most cases of pediatric ethylene glycol poisoning if treated with fomepizole. FOMEPIZOLE PHARMACOKINETICS: Plasma fomepizole concentrations were measured in three cases and were found to be therapeutic with apparent Michaelis-Menton kinetics, having a zero-order elimination rate of 0.6-1 mg/L/h at higher concentrations and a first-order elimination with an apparent elimination half-time of 3.9 h at lower concentrations. FOMEPIZOLE REGIMEN: Most cases used the current U.S.-approved regimen. ADVERSE EFFECTS OF FOMEPIZOLE: The one adverse effect reported during fomepizole therapy was transient nystagmus in a 6-year-old with a serum ethylene glycol concentration of 130 mg/L and a serum bicarbonate concentration of 2 mEq/L; it is likely that ethylene glycol itself was the cause. COMPARISON OF FOMEPIZOLE WITH ETHANOL THERAPY: Two cases were originally treated with ethanol but switched to fomepizole because of adverse effects. In both cases, the adverse reactions to ethanol resolved once fomepizole treatment was initiated. CONCLUSIONS: The limited data available suggest that fomepizole, using the same dosage regimen as that used for adults, is efficacious and well tolerated in pediatric patients. In many cases of pediatric ethylene glycol poisoning treated with fomepizole, hemodialysis may not be necessary despite high concentrations and the presence of metabolic acidosis. PMID- 20586571 TI - Colchicine poisoning: the dark side of an ancient drug. AB - INTRODUCTION: Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome. METHODS: We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication." TOXICOKINETICS: Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg. DRUG INTERACTIONS: CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy. MECHANISMS OF TOXICITY: Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation. CLINICAL FEATURES: Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness. DIAGNOSIS: History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia). MANAGEMENT: Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available. CONCLUSION: Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed. PMID- 20586572 TI - Poison center surveillance data: the good, the bad and ... the flu. AB - BACKGROUND: Poison center data are increasingly used by state health departments and the Centers for Disease Control and Prevention for public health surveillance. Forrester and colleagues evaluated the ability of 6 Texas poison centers covering a population of 24 million to accurately code and report the number of H1N1 calls received over a 5-month period. DISCUSSION: The Texas poison centers generated new coding and began work within 24 h of notification of the surveillance need. No additional staff were added for call management, coding, or quality assurance, and no H1N1 training was provided ahead of time. A triple redundancy coding method was used to prevent underreporting of calls. This allowed the Texas poison centers to accurately flag over 90% of H1N1 cases. Results were available in real time, allowing day-to-day monitoring by poison centers and the state public health department for surges, location, ages of callers and/or patients, and type of question. CONCLUSION: The accuracy of poison center near real-time toxicosurveillance data coding was sufficient to monitor emerging trends. The data generated by poison centers are flexible, immediate, unique from other data sources, and useful for trend monitoring. As health departments and other collaborative partners rely more on the data from poison centers, consideration must be given to appropriate funding to support coding training, monitoring, and quality assurance to further enhance this valuable system. PMID- 20586573 TI - Ingestion of false hellebore plants can cross-react with a digoxin clinical chemistry assay. AB - INTRODUCTION: We report a case of digoxin-like toxicity because of ingestion of foraged plants. This patient presented with nausea, vomiting, bradycardia, and hypotension after ingesting Veratrum viride (false hellebore). The patient's serum specimen demonstrated a positive digoxin level (0.38 ng/mL) measured by a clinical tubidimetric immunoassay. We hypothesize that steroidal alkaloid compounds contained in V. viride cross-react with the Multigent Digoxin immunoassay reagent antibodies. RESULTS: Plant extracts from V. viride demonstrated cross-reactivity to Multigent reagent antibodies but did not bind therapeutic DigiFab antibodies. Gas chromatography/mass spectrometry analyses identified several steroidal alkaloid compounds present in the V. viride extracts: jervine, ribigirvine, solanidine, and veratraman. CONCLUSIONS: This study indicates that compounds extracted from V. viride can cross-react with a clinical Digoxin immunoassay. Yet these extracts did not bind DigiFab antibody fragments used for therapeutic intervention. Providers should not unnecessarily administer DigiFab fragments as an antidote in symptomatic V. viride toxic patients. PMID- 20586574 TI - Fatality from acute chlorfenapyr poisoning. PMID- 20586575 TI - Etofenamate associated with Lyell syndrome: a case report. AB - Toxic epidermal necrolysis (Lyell syndrome) is a rare, acute, and potentially life-threatening mucocutaneous disease that is most often triggered by drugs. This is the first case of toxic epidermal necrolysis because of treatment with etofenamate of which we are aware. PMID- 20586577 TI - Plasmid segregation: how to survive as an extra piece of DNA. AB - Non-essential extra-chromosomal DNA elements such as plasmids are responsible for their own propagation in dividing host cells, and one means to ensure this is to carry a miniature active segregation system reminiscent of the mitotic spindle. Plasmids that are maintained at low numbers in prokaryotic cells have developed a range of such active partitioning systems, which are characterized by an impressive simplicity and efficiency and which are united by the use of dynamic, nucleotide-driven filaments to separate and position DNA molecules. A comparison of different plasmid segregation systems reveals (i) how unrelated filament forming and DNA-binding proteins have been adopted and modified to create a range of simple DNA segregating complexes and (ii) how subtle changes in the few components of these DNA segregation machines has led to a remarkable diversity in the molecular mechanisms of closely related segregation systems. Here, our current understanding of plasmid segregation systems is reviewed and compared with other DNA segregation systems, and this is extended by a discussion of basic principles of plasmid segregation systems, evolutionary implications and the relationship between an autonomous DNA element and its host cell. PMID- 20586578 TI - Chemical basis for minimal cognition. AB - We have developed a simple chemical system capable of self-movement in order to study the physicochemical origins of movement. We propose how this system may be useful in the study of minimal perception and cognition. The system consists simply of an oil droplet in an aqueous environment. A chemical reaction within the oil droplet induces an instability, the symmetry of the oil droplet breaks, and the droplet begins to move through the aqueous phase. The complement of physical phenomena that is then generated indicates the presence of feedback cycles that, as will be argued, form the basis for self-regulation, homeostasis, and perhaps an extended form of autopoiesis. We discuss the result that simple chemical systems are capable of sensory-motor coupling and possess a homeodynamic state from which cognitive processes may emerge. PMID- 20586579 TI - Concurrency and network disassortativity. AB - The relationship between a network's degree-degree correlation and a loose version of graph coloring is studied on networks with broad degree distributions. We find that, given similar conditions on the number of nodes, number of links, and clustering levels, fewer colors are needed to color disassortative than assortative networks. Since fewer colors create fewer independent sets, our finding implies that disassortative networks may have higher concurrency potential than assortative networks. This in turn suggests another reason for the disassortative mixing pattern observed in biological networks such as those of protein-protein interaction and gene regulation. In addition to the functional specificity and stability suggested by Maslov and Sneppen, a disassortative network topology may also enhance the ability of cells to perform crucial tasks concurrently. Hence, increased concurrency may also be a driving force in the evolution of biological networks. PMID- 20586582 TI - Abstracts of the 2010 NATA (National Athletic Trainers' Association) Annual Meeting and Clinical Symposia. June 23-25, 2010. Philadelphia, Pennsylvania, USA. PMID- 20586583 TI - Hyperoxia sensing: from molecular mechanisms to significance in disease. AB - Oxygen therapy using mechanical ventilation with hyperoxia is necessary to treat patients with respiratory failure and distress. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), causing cellular damage and multiple organ dysfunctions. As the lungs are directly exposed, hyperoxia can cause both acute and chronic inflammatory lung injury and compromise innate immunity. ROS may contribute to pulmonary oxygen toxicity by overwhelming redox homeostasis, altering signaling cascades that affect cell fate, ultimately leading to hyperoxia-induced acute lung injury (HALI). HALI is characterized by pronounced inflammatory responses with leukocyte infiltration, injury, and death of pulmonary cells, including epithelia, endothelia, and macrophages. Under hyperoxic conditions, ROS mediate both direct and indirect modulation of signaling molecules such as protein kinases, transcription factors, receptors, and pro- and anti-apoptotic factors. The focus of this review is to elaborate on hyperoxia-activated key sensing molecules and current understanding of their signaling mechanisms in HALI. A better understanding of the signaling pathways leading to HALI may provide valuable insights on its pathogenesis and may help in designing more effective therapeutic approaches. PMID- 20586584 TI - The FIMTM as a measure of change in function after discharge from inpatient rehabilitation: a Canadian perspective. AB - PURPOSE: To examine the FIMTM as an outcome measure at follow-up following discharge from inpatient rehabilitation. METHODS: Secondary analysis of the National Rehabilitation Reporting System (NRS) data from 13 facilities across Canada that collected follow-up data between 2001 and 2006. The study sample included all NRS records with a hospital length of stay of at least 3 days, for individuals 18 years and older. Outcomes included: mean total, motor and cognitive FIMTM scores at admission, discharge, and follow-up; change in FIMTM scores from admission to discharge and from discharge to follow-up; correlation between FIMTM scores at admission, discharge and follow-up, and predictors of the change in FIMTM scores between discharge and follow-up. RESULTS: The majority of the change in FIMTM scores is seen between admission and discharge with the higher FIM scores maintained, if not increased slightly, between discharge and follow-up. Discharge and follow-up total FIMTM scores are highly correlated indicating that collection of the follow-up FIMTM may not provide additional information that justifies the expense of data collection after a patient has been discharged from inpatient rehabilitation. CONCLUSIONS: The use of more appropriate rehabilitation follow-up outcomes needs to be considered. PMID- 20586585 TI - Barriers to adoption of evidence-based prehospital airway management practices in California. AB - OBJECTIVE: To describe current prehospital airway management practices for adults and children and barriers to adoption of evidence-based airway management practices in California. METHODS: We surveyed local medical directors of California's 31 emergency medical services (EMS) agencies regarding prehospital airway management, including provider scope of practice, continuous quality improvement practices, and perceptions regarding barriers to the implementation of evidence-based airway management practices. The survey instrument was a Web based, closed-response form ( www.surveymonkey.com ) that medical directors could access by an e-mailed link provided by investigators. Medical directors were contacted by phone, mail, and e-mail to request their participation in the Web based survey. RESULTS: Twenty-five of 31 (81%) EMS medical directors completed the survey. Five medical directors completed surveys for two agencies over which they had responsibility. All responding medical directors employ bag-mask ventilation (BMV), airway adjuncts, and adult endotracheal intubation (ETI), which are procedures widely accepted in EMS practice. Rapid-sequence intubation (RSI), which has been shown to cause harm in certain patient subgroups, was not employed by any of the respondents. Prehospital pediatric ETI, which has been shown not to provide any benefit over BMV, was employed by 22 of 25 (88%) medical directors. Thirteen of 23 (57%) respondents identified "more evidence is needed" or "these results do not apply to my EMS system" as the top reasons to continue the practice of prehospital pediatric ETI. CONCLUSIONS: The results of our study suggest that in areas of EMS where robust evidence exists, medical directors (100%) will discontinue or not adopt skills that potentially harm patients, such as RSI, but are unlikely (12%) to discontinue procedures that show no benefit to patients (such as pediatric ETI). Barriers to adoption of evidence-based practice include difficulty in generalizing results of studies across diverse EMS systems and perceived lack of evidence that the procedure should be abandoned. PMID- 20586586 TI - Injury hospitalization as a marker for emergency medical services use in elderly patients. AB - BACKGROUND: The elderly utilize emergency medical services (EMS) at a higher rate than younger patients, yet little is known about the influence of injury on subsequent EMS utilization and costs. OBJECTIVE: To assess injury hospitalization as a potential marker for subsequent EMS utilization and costs by Medicare patients. METHODS: This observational study analyzed a retrospective cohort of all Medicare patients (> or = 67 years old) with an International Classification of Diseases, Ninth Revision (ICD-9) injury diagnosis admitted to 125 Oregon and Washington hospitals during 2001 and 2002 who survived to hospital discharge. The numbers of EMS transports and the total EMS costs were compared one year before and one year following the index hospitalization. RESULTS: There were 30,655 injured elders in our cohort. Their median ICD-9-based injury severity score was 0.97, with 4.1% meeting a definition of serious injury and 37% having hip fractures. The mean (range) numbers of EMS transports before and after the injury were 0.5 (0-45) and 0.9 (0-56), for an unadjusted incidence rate ratio (IRR) of 1.7 (95% confidence interval [CI] 1.7-1.8). The increase in EMS utilization following an injury hospitalization was even greater after adjusting for risk period and other model predictors (IRR 2.4, 95% CI 2.3-2.5). Annual mean EMS costs rose 74% following the injury hospitalization, from $211 to $367 per person. The greatest increase was in nonemergent EMS use, accounting for 67% of the increase in the number of uses. Institutionalization in a skilled nursing or rehabilitation facility either before or after injury was strongly associated with the need for EMS care. CONCLUSION: An injury hospitalization in the elderly serves as a sentinel marker for an abrupt increase in EMS utilization and costs, even after accounting for confounders. PMID- 20586587 TI - Comparison of three airway management techniques in a simulated tactical setting. AB - INTRODUCTION: Several different methods for emergent airway management are feasible in the tactical environment. Current studies fail to identify which method minimizes the exposure of the tactical medic or which is most rapid with the greatest chance of first-attempt success. METHODS: We evaluated three commonly used airway management techniques, including standard direct laryngoscopy with endotracheal intubation, digital endotracheal intubation, and use of the King LT laryngotracheal airway device. Study participants were volunteer emergency medicine (EM) residents and medical flight crew members with difficult airway management skills. We compared the times to successful ventilation, numbers of attempts to successful ventilation, and heights of presentation of the participants above a barricade used to simulate concealment. RESULTS: Thirty-one subjects completed the study, of whom 12 (39%) were medical flight crew members and 19 (61%) were EM residents. All subjects were able to successfully ventilate manikins using each of the three methods. The mean number of attempts to intubate and ventilate the manikin was 1.03 for direct laryngoscopy, 1.26 for the King LT, and 1.67 for digital endotracheal intubation. Mean time to ventilation was 59.7 seconds for the King LT, 63.3 seconds for laryngoscopy, and 125.4 seconds for digital intubation. The maximum height the medic reached above the barricade during airway management was 17.7 inches for the King LT, 19.7 inches for laryngoscopy, and 23.5 inches for digital intubation. Comparison of all three factors across groups showed significance, with the exception of time to ventilation between laryngoscopy and use of the King LT. CONCLUSION: In a simulated tactical airway management scenario, use of the King LT provided less exposure than digital or standard endotracheal intubation techniques. Digital intubation behind the simulated barricade was the least successful by all measures. Although direct laryngoscopy was the most successful on the first attempt, use of the King LT in our scenario provided the least exposure of the medic and was as effective as direct laryngoscopy with regard to time to ventilation. Key words: TEMS; airway management; simulation; tactical environment; combat medicine. PMID- 20586588 TI - Out-of-hospital diagnosis of a ruptured ectopic pregnancy: myometrial embryo implantation, an exceptional diagnosis. AB - BACKGROUND: Ultrasonography (US) could be used in emergency out-of-hospital settings to diagnose abdominal hemorrhage. OBJECTIVES: To report the diagnosis by US of a suspected case of ruptured ectopic pregnancy despite a supposedly in utero pregnancy. CASE REPORT: A mobile intensive care unit with an emergency physician on board was sent out to a 22-year-old woman suffering from acute abdominal pain. On the previous day, an 11-week pregnancy had been diagnosed and the pelvic US images were reported to be "normal." Physical examination revealed that the patient was in shock. Point-of-care US detected an intraperitoneal effusion and suspected uterine rupture. Emergency laparotomy revealed an 11- or 12-week intra-abdominal pregnancy with uterine rupture due to myometrial implantation of the embryo. CONCLUSION: Ultrasound is a helpful tool in emergency care, particularly in out-of-hospital settings. An earlier "normal" US examination cannot definitively exclude uterine rupture. PMID- 20586589 TI - 50th anniversary of the Silver Hut expedition. PMID- 20586592 TI - Altitude preexposure recommendations for inducing acclimatization. AB - For many low-altitude (<1500 m) residents, their travel itineraries may cause them to ascend rapidly to high (>2400 m) altitudes without having the time to develop an adequate degree of altitude acclimatization. Prior to departing on these trips, low-altitude residents can induce some degree of altitude acclimatization by ascending to moderate (>1500 m) or high altitudes during either continuous or intermittent altitude preexposures. Generally, the degree of altitude acclimatization developed is proportional to the altitude attained and the duration of exposure. The available evidence suggests that continuous residence at 2200 m or higher for 1 to 2 days or daily 1.5- to 4-h exposures to >4000 m induce ventilatory acclimatization. Six days at 2200 m substantially decreases acute mountain sickness (AMS) and improves work performance after rapid ascent to 4300 m. There is evidence that 5 or more days above 3000 m within the last 2 months will significantly decrease AMS during a subsequent rapid ascent to 4500 m. Exercise training during the altitude preexposures may augment improvement in physical performance. The persistence of altitude acclimatization after return to low altitude appears to be proportional to the degree of acclimatization developed. The subsequent ascent to high altitude should be scheduled as soon as possible after the last altitude preexposure. PMID- 20586593 TI - The Silver Hut expedition, 1960-1961. AB - The 1960-1961 Himalayan Scientific and Mountaineering Expedition, commonly known as the Silver Hut Expedition, was a unique project to study the physiology of acclimatization in human lowlander subjects at extreme altitude over a prolonged period and also to make an attempt on Makalu, an 8470-m peak. The leader was Sir Edmund Hillary, and Dr. Griffith Pugh was the scientific leader. Studies were conducted at a Base Camp in the Everest region of Nepal at 4500 m and at the Silver Hut at 5800 m on the Mingbo Glacier. Simpler physiology was continued on Makalu, in camps at 6300 and 7400 m. The expedition left Kathmandu at the end of the monsoon in 1960 and spent the autumn setting up the Base Camp and the Silver Hut. Some members also spent time making a study of the evidence for the existence of the Yeti. The winter was spent on physiological studies at Base Camp and in the Silver Hut, and the nearby peak of Ama Dablam was climbed. In the spring the expedition moved over to Makalu and made an unsuccessful attempt to climb it without supplementary oxygen. The 9-month expedition ended at the start of the 1961 monsoon. An ambitious program of studies was successfully completed. It was a very happy and, scientifically, a successful expedition. Many of the findings were not repeated for many years, and none has been refuted. On the mountaineering side, we were unsuccessful on Makalu owing to a combination of weather and illness, but the ascent of Ama Dablam was considerable compensation. PMID- 20586594 TI - American medical research expedition to Everest. AB - The primary objective of the American Medical Research Expedition to Everest was to obtain information on human physiology at the highest possible altitude, including the Everest summit. An important data point was the barometric pressure on the summit, because this determines the inspired P(O(2)). The first measurement ever taken was 253.0 mmHg. Because modeling studies had shown that extreme hyperventilation was essential to reach these great altitudes, 34 alveolar gas samples were collected above an altitude of 8000 m, including 4 on the summit. These showed that hyperventilation reduced the alveolar P(CO(2)) to between 7 and 8 mmHg in one climber. An important finding was that alveolar P(O(2)) was defended at a value of about 35 mmHg by the increasing hyperventilation as the climbers ascended higher. Venous blood samples collected on two summiters gave a mean base excess of -7.2 meq.L(-1). Using the alveolar P(CO(2)) value, this gave an arterial pH of over 7.7, indicating an extreme degree of respiratory alkalosis. While climbing at an altitude of 8300 m, one summiter showed a respiratory frequency of 86 breaths.min(-1) and tidal volume of 1.26 L, indicating very rapid shallow breathing. Maximal oxygen consumption for the summit was derived by having well-acclimatized subjects exercise maximally at an altitude of 6300 m while breathing 14% oxygen. The V(O(2)) was just over 1 L.min(-1), which is sufficient to explain how exceptional humans can reach the summit without supplementary oxygen. In addition to the measurements at altitudes over 8000 m, data were obtained at two camps at 5400- and 6300-m altitude. These gave information on the control of ventilation, periodic breathing, blood physiology, cerebral function, and metabolism. PMID- 20586595 TI - Operation Everest II. AB - In October 1985, 25 years ago, 8 subjects and 27 investigators met at the United States Army Research Institute for Environmental Medicine (USARIEM) altitude chambers in Natick, Massachusetts, to study human responses to a simulated 40-day ascent of Mt. Everest, termed Operation Everest II (OE II). Led by Charlie Houston, John Sutton, and Allen Cymerman, these investigators conducted a large number of investigations across several organ systems as the subjects were gradually decompressed over 40 days to the Everest summit equivalent. There the subjects reached a V(O)(2)max of 15.3 mL/kg/min (28% of initial sea-level values) at 100 W and arterial P(O(2)) and P(CO(2)) of approximately 28 and approximately 10 mm Hg, respectively. Cardiac function resisted hypoxia, but the lungs could not: ventilation-perfusion inequality and O(2) diffusion limitation reduced arterial oxygenation considerably. Pulmonary vascular resistance was increased, was not reversible after short-term hyperoxia, but was reduced during exercise. Skeletal muscle atrophy occurred, but muscle structure and function were otherwise remarkably unaffected. Neurological deficits (cognition and memory) persisted after return to sea level, more so in those with high hypoxic ventilatory responsiveness, with motor function essentially spared. Nine percent body weight loss (despite an unrestricted diet) was mainly (67%) from muscle and exceeded the 2% predicted from energy intake-expenditure balance. Some immunological and lipid metabolic changes occurred, of uncertain mechanism or significance. OE II was unique in the diversity and complexity of studies carried out on a single, courageous cohort of subjects. These studies could never have been carried out in the field, and thus complement studies such as the American Medical Research Expedition to Everest (AMREE) that, although more limited in scope, serve as benchmarks and reality checks for chamber studies like OE II. PMID- 20586596 TI - Operation Everest III: COMEX '97. AB - Eight male volunteers, aged 23 to 37, were selected to participate in a simulated ascent to 8848 m in a hypobaric chamber. They were first preacclimatized in the Observatoire Vallot (4350 m) before entering the chamber. The chamber was progressively decompressed down to 253 mmHg barometric pressure, with a recovery period of 3 days at 5000 m from days 20 to 22. They spent a total of 31 days in the chamber. Seventeen protocols were organized by 14 European teams to explore the limiting factors of physical and psychological performance and the physiological and pathological changes in various systems (cardiac function, control of ventilation, autoregulation of cerebral blood flow, energy balance and body composition, muscle performance, erythropoiesis, and cognitive functions). All subjects reached 8000 m, and 7 of them reached the simulated altitude of 8848 m. Three subjects complained of transient neurological symptoms, which resolved rapidly with reoxygenation. At 8848 m (n = 5), Pa(O(2)) was 30.6 +/- 1.4 mmHg, Pc(O(2)) was 11.9 +/- 1.4 mmHg, and pH was 7.58 +/- 0.02 (arterialized capillary blood). V(O(2))max decreased by 59% at 7000 m and increased by 9% at 6000 m after plasma expansion, suggesting a role of altitude-induced plasma contraction in the reduction in V(O(2))max. Cardiac contractility was normal, but relaxation was slightly impaired. Autoregulation of cerebral blood flow was impaired at 8000 m. Negative energy balance was essentially caused by a decrease in appetite. Increased membrane lipid peroxidation could explain alterations in muscle or cognitive function. The subjects reached the "summit" in better physiological conditions than would have been possible in the mountains, probably because acclimatization and other environmental factors such as cold and nutrition were controlled. PMID- 20586598 TI - The impact of moderate-altitude staging on pulmonary arterial hemodynamics after ascent to high altitude. AB - Staged ascent (SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure (PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent (DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximately 760 torr), after DA to simulated high altitude (hypobaric chamber, P(B) approximately 460 torr), and at 2 times points (90 min and 4 days) during exposure to terrestrial high altitude (P(B) approximately 460 torr) after SA (7 days, moderate altitude, P(B) approximately 548 torr). Alveolar oxygen pressure (Pao(2)) and arterial oxygenation saturation (Sao(2)) were measured at each time point. Compared to mean PAP at SL (mean +/- SD, 14 +/- 3 mmHg), mean PAP increased after DA to 37 +/- 8 mmHg (Delta = 24 +/- 10 mmHg, p < 0.001) and was negatively correlated with both Pao(2) (r(2) = 0.57, p = 0.011) and Sao(2) (r(2) = 0.64, p = 0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4 mmHg (Delta = 11 +/- 6 mmHg, p < 0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5 mmHg, p = not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia. PMID- 20586597 TI - Caudwell xtreme Everest expedition. AB - The Caudwell Xtreme Everest (CXE) expedition involved the detailed study of 222 subjects ascending to 5300 m or higher during the first half of 2007. Following baseline measurements at sea level, 198 trekker-subjects trekked to Everest Base Camp (EBC) following an identical ascent profile. An additional group of 24 investigator-subjects followed a similar ascent to EBC and remained there for the duration of the expedition, with a subgroup of 14 collecting data higher on Everest. This article focuses on published data obtained by the investigator subjects at extreme altitude (>5500 m). Unique measurements of peak oxygen consumption, middle cerebral artery diameter and blood velocity, and microcirculatory blood flow were made on the South Col (7950 m). Unique arterial blood gas values were obtained from 4 subjects at 8400 m during descent from the summit of Everest. Arterial blood gas and microcirculatory blood flow data are discussed in detail. PMID- 20586599 TI - Fatal accidents among elite mountaineers: A historical perspective from the European Alps. AB - The lifetime risk of a fatal mountain accident among elite European alpine mountaineers and its time trends are determined by studying a fixed cohort of 390 elite mountaineers listed in the Encyclopaedia of the Alps (Hiebler, 1977). At publication of the encyclopaedia, 158 individuals were still living and were followed up until the end of 2008. The crude lifetime risk of a fatal accident for elite mountaineers is 0.203 [95% confidence interval (CI), 0.165 to 0.246). The difference in mortality between male (0.207; 95% CI: 0.168 to 0.251) and female mountaineers (0.118; 95% CI: 0.033 to 0.343) is not statistically significant. No fatal accidents occurred among elite mountaineers born before 1820. For the birth cohort from 1820 to 1949, the lifetime risk of a fatal accident (male mountaineers only) increased with time from 0.069 (95% CI, 0.019 to 0.220) to 0.375 (95% CI, 0.212 to 0.573). For all time strata, the highest risk of a fatal mountain accident was observed at an age of 30 to 39 yr. The high mortality among elite mountaineers clearly demonstrates that the limits of human performance are reached by these activities. The high risks should be communicated and should motivate risk-reduction efforts for this highly exposed subgroup of mountaineers. PMID- 20586601 TI - Initial orthostatic hypotension at high altitude. AB - There are several reports on syncope occurring following standing at high altitude (HA), yet description of the detailed physiological responses to standing at HA are lacking. We examined the hypothesis that appropriate physiological adjustments to upright posture would be compromised at HA (5050 m). Ten healthy volunteers stood up rapidly from supine rest, for 3 min, at sea level and at 5050 m. Beat-to-beat mean arterial blood pressure (MAP, Finometer), middle cerebral artery blood velocity (MCAv, Transcranial Doppler), end-tidal PCO(2) and PO(2), and heart rate (ECG) were recorded continuously. After 14 days at HA, baseline MAP and MCAv were not different to sea level, although HR was elevated. Neither the magnitude of initial (<15 s) responses to standing, nor the time course of initial recovery differed at HA compared with sea level (p > 0.05). By 3 min of standing, MAP was restored to supine values both at sea level (-3 +/- 12 mmHg) and HA (4 +/- 10 mmHg), although there was more complete recovery of HR at sea level (+13 +/- 10 b.min(-1), p = 0.02 vs. + 23 +/- 10 b.min(-1), p = 0.01). Reduced MCAv at 3 min was comparable at sea level and altitude (both -16%). These data indicate that initial cardiovascular and cerebrovascular responses to standing are unaltered when partially acclimatized to HA. PMID- 20586600 TI - PKC regulates alpha(1)-adrenoceptor-mediated contractions and baseline Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia. AB - Chronic hypoxia has a profound effect on uterine artery adaptation to pregnancy. The present studies tested the hypothesis that pregnant kinase C (PKC) differentially regulates alpha(1)-adrenoceptor-mediated contractions and Ca(2+) sensitivity in the uterine arteries of nonpregnant and pregnant sheep acclimatized to high altitude hypoxia. Uterine arteries were isolated from nonpregnant (NPUA) and near-term pregnant (PUA) ewes maintained at high altitude (3801 m, Pao(2) approximately 60 torr) for 110 days. Phorbol 12,13-dibutyrate (PDBu) decreased phenylephrine-induced contractions in PUA but not in NPUA, which was partly inhibited by the PKC inhibitor GF109203X. Additionally, GF109203X shifted the concentration-response curve of phenylephrine-induced contractions to the right in PUA. In beta-escin-permeabilized arteries, Ca(2+)-induced increases in 20-kDa myosin light chain phosphorylation (MLC(20)-P) were similar in NPUA and PUA. However, Ca(2+) produced a concentration-dependent increase in the ratio of tension to MLC(20)-P in PUA, as compared with NPUA. PKC inhibition decreased Ca(2+)-induced contractions in both NPUA and PUA. PDBu induced contractions of PUA in the absence of changes in MLC(20)-P, which was not affected by PD098059. There was a significant increase in the basal activity of PKCvarepsilon in PUA, but not in NPUA, in hypoxic sheep, as compared with normoxic animals. The results demonstrate that the inhibitory effect of PKC on alpha(1)-adrenoceptor-mediated contractions of uterine arteries is preserved in pregnant sheep at high altitude. However, the PKC-mediated thin-filament regulatory pathway is upregulated, resulting in increased baseline Ca(2+) sensitivity in the uterine artery during pregnancy at high altitude. PMID- 20586602 TI - English translation of "Nomenclature, classification, and diagnostic criteria of high altitude disease in China". PMID- 20586603 TI - Plasticity of oxidative metabolism in variable climates: molecular mechanisms. AB - Converting food to chemical energy (ATP) that is usable by cells is a principal requirement to sustain life. The rate of ATP production has to be sufficient for housekeeping functions, such as protein synthesis and maintaining membrane potentials, as well as for growth and locomotion. Energy metabolism is temperature sensitive, and animals respond to environmental variability at different temporal levels, from within-individual to evolutionary timescales. Here we review principal molecular mechanisms that underlie control of oxidative ATP production in response to climate variability. Nuclear transcription factors and coactivators control expression of mitochondrial proteins and abundance of mitochondria. Fatty acid and phospholipid concentrations of membranes influence the activity of membrane-bound proteins as well as the passive leak of protons across the mitochondrial membrane. Passive proton leak as well as protein mediated proton leak across the inner mitochondrial membrane determine the efficacy of ATP production but are also instrumental in endothermic heat production and as a defense against reactive oxygen species. Both transcriptional mechanisms and membrane composition interact with environmental temperature and diet, and this interaction between diet and temperature in determining mitochondrial function links the two major environmental variables that are affected by changing climates. The limits to metabolic plasticity could be set by the production of reactive oxygen species leading to cellular damage, limits to substrate availability in mitochondria, and a disproportionally large increase in proton leak over ATP production. PMID- 20586604 TI - Discrimination of relapsing fever Borrelia persica and Borrelia microtti by diagnostic species-specific primers and polymerase chain reaction-restriction fragment length polymorphism. AB - Tick-borne relapsing fever (TBRF) is endemic in Africa and Eurasia and attributed to different Borrelia species. In the Central Asia and Middle Eastern countries, TBRF is caused mainly by Borrelia persica; however, other Borrelia species such B. microtti, B. latyschewii, B. baltazardi, and B. caucasica have also been described. The classic taxonomy of Borrelia spp. is based on the cospeciation concept that is very complex and rather confusing. In this study, we report two DNA-based methods to discriminate B. persica and B. microtti, the two main prevalent species in the region. Molecular typing of the species was performed using (i) restriction fragment length polymorphism analysis of polymerase chain reaction (PCR)-amplified fragments of either 16S-rRNA or glpQ genes, and (ii) species-specific PCR of glpQ gene. Sequence analyses of the data obtained in this study indicate that the glpQ gene is more variable than 16S-rRNA (6.9% vs. 1.2%); thus glpQ is a more useful marker for discrimination of B. persica from B. microtti. The 16S-rRNA fragment comprises only one useful species-specific restriction site (TaqI), whereas the glpQ fragment includes several species specific restriction sites and its digestion by DraI, TaqI, EcoRV, HinfI, or SspI results in distinctively different PCR-restriction fragment length polymorphism patterns for the two species. Further, the species-specific primers amplified a 253-bp fragment for B. persica and a 451-bp one for B. microtti. Phylogenetic analysis of the data revealed that B. microtti and B. persica are associated to the African and new world RF agents, respectively. This study demonstrates that both typing methods are simple, sensitive, and fast, and that they allow one to differentiate between B. persica and B. microtti. This could prove that both methods are important and useful in monitoring of TBRF disease in endemic areas. PMID- 20586605 TI - Molecular epidemiological investigation of Plasmodium knowlesi in humans and macaques in Singapore. AB - Singapore reported its first locally acquired human Plasmodium knowlesi infection in 2007, involving a soldier who had undergone training in a forested area where long-tailed macaques are frequently seen. Comprehensive disease surveillance and monitoring system that was set up after the initial case detected four additional human P. knowlesi cases in 2007 and one in 2008. All involved military personnel who had undergone training in the forested area, and none had traveled out of Singapore 1 month before the onset of symptoms. Screening for malaria parasites on blood obtained from long-tailed macaques revealed that wild monkeys (n=3) caught from the forested area were infected with P. knowlesi, whereas peri domestic monkeys (n=10) caught from a nature reserve park were not infected with any malaria parasites. Phylogenetic analysis of the nonrepeat region of the P. knowlesi csp genes showed that the sequences obtained from the human cases were not distinct from those obtained from wild monkeys. Further, certain genotypes were shared between samples from humans and macaques. Our findings provide evidence that long-tailed macaques are the natural hosts of P. knowlesi in Singapore and the human cases acquired their infection in the same vicinity where these monkeys are found. Further, the risk of acquiring P. knowlesi infection among the general population of Singapore is small as evident from the absence of P. knowlesi in peri-domestic monkeys. PMID- 20586606 TI - Rickettsia felis in fleas from Catalonia (Northeast Spain). AB - INTRODUCTION: Rickettsia felis produces a syndrome indistinguishable from murine typhus, which has been described in Spain. R. felis is transmitted to humans by fleas. Although no clinical case has been described so far, serologic evidence of infections in humans, cats, and dogs has been obtained in our area. However, no study has been conducted regarding its presence in vectors. Recognition of routes of transmission is of great importance to prevent infection in humans. Taking into account these results, R. felis seems to be present in animals that are in contact with humans. The aim of this study was to determine the presence of R. felis in the fleas of cats and dogs from Northeast Spain, to show the presence of peridomestic cycle in our area. MATERIALS AND METHODS: Between May 2006 and July 2008, 78 fleas were collected. Sixty-three fleas were recovered from kennels. Most of them were collected from cages and a few of them on dogs and cats living in kennels. Fifteen fleas were collected from dogs and cats attended at a veterinary clinic. Fleas were rinsed with ethanol, dried, identified, and stored at 4 degrees C. DNA was extracted from each flea individually. Rickettsial DNA was determined by quantitative real-time polymerase chain reaction. OmpB-specific primers and molecular beacon probes targeting specifically R. felis were used. RESULTS: All 78 fleas were identified as Ctenocephalides felis. R. felis was detected in 34 (43.6%) fleas. No nucleic acids were amplified from negative controls and expected results were obtained from positive controls. Eight positive samples were also confirmed by sequencing. CONCLUSIONS: R. felis was found in a high percentage of Ct. felis from cats and dogs. It seems that there is a peridomestic cycle in Northeast Spain, which would allow contact of R. felis with humans. PMID- 20586607 TI - Malaria and the campaigns toward its eradication in Romania, 1923-1963. AB - Malaria was common in Romania until largely successful campaigns of the 20th century. Researchers Ioan Cantacuzino, George Zotta, and Mihai Ciuca carried out important early contributions to the understanding of malarial endemo-epidemic situation in Romania. The malarial endemy registered a peak in 1942 with an incidence of 1218 cases per 100,000 inhabitants as a result of the disastrous effects of the Second World War. In the following years the incidence increased from 421.5 cases per 100,000 inhabitants in 1944 to 735.1 cases per 100,000 inhabitants in 1946. A Malaria Commission was formed in February 1947 with the mission to reorganize the fight against malaria in Romania based on international guidelines. Following the adoption of proper malarial eradication methods, namely coverage of endemic areas by spraying of residual insecticides, associated with chemotherapy and, eventually, chemoprophylaxis with synthetic products, and by surveillance, indigenous cases disappeared rapidly, relapsing cases were much reduced, and imported and induced cases remained constant or even increased slightly, probably due to the increase in traffic and in the use of blood transfusions. No indigenous cases have been registered in Romania since 1962. In 1963 the Romanian authorities declared malarial eradication in the territory to the World Health Organization. PMID- 20586608 TI - Effectiveness of pulsed ultraviolet-light treatment for bacterial inactivation on agar surface and liquid medium. AB - In the present study, the efficiency of a broad-spectrum pulsed ultraviolet (UV) light for the inactivation of Listeria monocytogenes Scott A, L. monocytogenes CNL 895807, and Pseudomonas fluorescens MF37 populations as agar seeded or suspended cells was investigated. The bacterial populations were treated by pulsed UV-light at different number of pulses (1 to 3), dose of energy (162, 243, or 324 J), and distance from the strobe (4, 9, or 12 cm). After pulsed UV-light treatment, the bacterial reduction was determined by standard plate count. The results showed that there was a significant reduction of population along with an increase of light energy and number of pulses. Decreasing the distance between the Petri dishes and the xenon lamp demonstrated an increase in bacterial reduction. Decontamination efficacy decreased significantly with the increase in level of contamination. This study demonstrates that pulsed UV-light can be used as an effective sterilizing method for the bacteria. PMID- 20586609 TI - Using outbreak data for source attribution of human salmonellosis and campylobacteriosis in Europe. AB - Salmonella and Campylobacter are the most important bacterial causes of foodborne illness in Europe. To identify and prioritize food safety interventions, it is important to quantify the burden of human foodborne illness attributable to specific sources. Data from outbreak investigations are observed at the public health endpoint and can therefore be a direct measure of attribution at the point of exposure. An analysis or summary of outbreak investigations is useful for attributing illnesses to foods, but often the implicated foods in reported outbreaks are complex foods, containing several food items, many of which could be the specific source of the infection. We describe a method that is able to attribute human cases to specific food items contained in complex foods. The model is based on data from investigations of Salmonella and Campylobacter outbreaks in the European Union in 2005 and 2006. The reporting of the causative vehicles for the outbreaks was not harmonized between and within countries. Consequently, we organized the implicated foods in mutually exclusive food categories. We estimated that the most important food sources for salmonellosis cases were eggs (32%) and meat and poultry-meat (15%), and that the majority of the cases of campylobacteriosis were attributed to chicken (10%). For both pathogens, a large proportion of cases could not be linked to any source. Among illnesses that could be attributed to a source, 58% of salmonellosis cases were attributed to eggs, and 29% of campylobacteriosis cases were attributed to chicken. Results also revealed regional differences in the relative importance of specific sources. We assessed the method to be of limited value to attribute human campylobacteriosis due to the limited number of outbreaks. Nevertheless, the presented source attribution approach can be applied to other foodborne pathogens, and is easily adaptable to countries having an appropriate number of reported outbreaks. PMID- 20586610 TI - Listeria monocytogenes infection in the over-60s in England between 2005 and 2008: a retrospective case-control study utilizing market research panel data. AB - A retrospective case-control study of listeriosis in patients in England aged over 60 years is described. The incidence of listeriosis in patients aged >=60 years in England has doubled since 2001; hence, the investigation of risk factors for infection in this group is important to inform on prevention and control. Standardized epidemiological information has been sought on cases since 2005, but the value of the data accrued is limited without some perception of exposure prevalence in the population at risk of listeriosis. The exposures of listeriosis cases aged >=60 years reported in England from 2005 to 2008 were compared to those of market research panel members representing the same population (i.e., residents of England aged >=60 years) and time period. Exposures were grouped to facilitate comparison. Odds ratios and 95% confidence intervals were calculated. Cases were more likely than panel members to report the consumption of cooked meats (beef and ham/pork, but not poultry), cooked fish (specifically smoked salmon) and shellfish (prawns), dairy products (most noticeably milk but also certain cheeses), and mixed salads. They were less likely to report the consumption of other forms of seafood, dairy spread, other forms of dairy, sandwiches, and fresh vegetables. The diversity of high-risk food exposures reflects the ubiquity of the microorganism in the environment and/or the susceptibility of those at risk, and suggests that a wider variety of foods can give rise to listeriosis. Food safety advice on avoiding listeriosis should be adapted accordingly. While not inexpensive, the application of market research data to infectious disease epidemiology can add value to routine surveillance data. PMID- 20586611 TI - Ectopic human mesenchymal stem cell-coated scaffolds in NOD/SCID mice: an in vivo model of the leukemia niche. AB - Human mesenchymal stem cells form the supportive structure in which the functional cells of a differentiated tissue reside. We describe the creation of ectopic niches within polyurethane scaffolds coated with human mesenchymal stem cells. When implanted subcutaneously in NOD/SCID mice, these niches supported engraftment of primary human acute myeloid leukemia cells. The scaffolds showed vascularization and presence of osteoclasts and adipocytes, suggestive of an organizing human bone marrow microenvironment in the murine host. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are critical for homing and migration of acute myeloid leukemia. We found that a CXCR4 antagonist could disrupt homing to the ectopic niches, possibly by modulation of the mesenchymal stroma. We believe that these scaffold niches provide a new and powerful tool to study the leukemia stem cell microenvironment and may be useful for identification of novel drug targets. PMID- 20586613 TI - A collagen-chitosan hydrogel for endothelial differentiation and angiogenesis. AB - Cell therapy for the treatment of cardiovascular disease has been hindered by low cell engraftment, poor survival, and inadequate phenotype and function. In this study, we added chitosan to a previously developed injectable collagen matrix, with the aim of improving its properties for cell therapy and neovascularization. Different ratios of collagen and chitosan were mixed and chemically crosslinked to produce hydrogels. Swell and degradation assays showed that chitosan improved the stability of the collagen hydrogel. In culture, endothelial cells formed significantly more vascular-like structures on collagen-chitosan than collagen only matrix. While the differentiation of circulating progenitor cells to CD31+ cells was equal on all matrices, vascular endothelial-cadherin expression was increased on the collagen-chitosan matrix, suggesting greater maturation of the endothelial cells. In addition, the collagen-chitosan matrix supported a significantly greater number of CD133+ progenitor cells than the collagen-only matrix. In vivo, subcutaneously implanted collagen-chitosan matrices stimulated greater vascular growth and recruited more von Willebrand factor (vWF+) and CXCR4+ endothelial/angiogenic cells than the collagen-only matrix. These results indicate that the addition of chitosan can improve the physical properties of collagen matrices, and enhance their ability to support endothelial cells and angiogenesis for use in cardiovascular tissue engineering applications. PMID- 20586612 TI - Knockouts of SOD1 and GPX1 exert different impacts on murine islet function and pancreatic integrity. AB - Metabolic subtlety and clinical relevance of different forms of reactive oxygen species in diabetes remain unclear. Using single knockout of Cu,Zn-superoxide dismutase (SOD1(-/-)) or Se-glutathione peroxidase-1 (GPX1(-/-)) and their double knockout (DKO) mouse models, we determined if elevating endogenously-derived superoxide and hydroperoxide exerted distinct impacts and mechanisms on body glucose homeostasis. Whereas the three knockout groups displayed decreased plasma insulin concentrations and islet beta-cells mass, only SOD1(-/-) showed decreased body weight, increased blood glucose, and blocked glucose-stimulated insulin secretion. Null of SOD1 and GPX1 elevated respective islet superoxide and hydroperoxide production, and upregulated p53 phosphorylation. Knockout of SOD1 downregulated the foxhead box A2/pancreatic and duodenal homeobox 1 pathway in a superoxide-dependent fashion at epigenetic, mRNA, and protein levels in islets, but improved insulin signaling in liver and muscle. The SOD1(-/-) mice showed more apparent pancreatitis than the GPX1(-/-) mice that were more susceptible to the cerulein-induced amylase increase. Knockout of SOD1 impaired islet function, pancreas integrity, and body glucose homeostasis more than that of GPX1. Simultaneous ablation of both enzymes did not result in additive or aggravated metabolic outcomes. PMID- 20586614 TI - Leucine-rich repeat (in Flightless I) interacting protein-1 regulates a rapid type I interferon response. AB - The cell autonomous response to viral infection is carefully regulated to induce type I interferons (IFNs), which in turn induce the establishment of an antiviral state. Leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) and LRRFIP2 are 2 related proteins that have been identified as interacting with MyD88 and Flightless I homolog, a leucine-rich repeat protein. LRRFIP2 positively regulates NFkappaB and macrophage cytokine production after lipopolysaccharide, but less is known about LRRFIP1. We hypothesized that LRRFIP1 could be more important in antiviral responses, as overexpression led to type I IFN production in a pilot study. The induction of type I IFNs occurred even in the absence of virus, but was enhanced by the presence of virus. Conversely, knockdown of LRRFIP1 compromised IFN expression. We found that LRRFIP1 was rapidly recruited to influenza-containing early endosomes in a p38-dependent fashion. This was specific for virus-containing endosomes as there was almost no colocalization of LRRFIP1 with early endosomes in the absence of virus. Further, LRRFIP1 was recruited to RNA-containing vesicles. Taken together, these data suggest that LRRFIP1 participates in cell responses to virus at early time points and is important for type I IFN induction. PMID- 20586615 TI - Modulation of cytokine production by cyclic adenosine monophosphate analogs in human leukocytes. AB - Cyclic adenosine monophosphate (cAMP) is a well-known second messenger that operates through different signaling molecules, including protein kinase A (PKA) and guanine exchange proteins directly activated by cAMP (EPAC). Cell-permeable cAMP analogs such as 8-(4-chloro-phenyl-thio)-cAMP (8-pCPT-cAMP) modulate cytokine secretion by different leukocyte subsets, including T cells and monocytes. Since cAMP-modulating drugs such as phosphodiesterase inhibitors are being tested in inflammatory disorders such as asthma and chronic obstructive lung disease, it is important to obtain more insight into the regulation of cytokine production by cAMP. To address the signaling molecules involved in cAMP mediated modulation of cytokine production, we used cAMP derivatives such as N(6) benzoyladenosine-cAMP (6-Bnz-cAMP) and 8-pCPT-2-O-methyl cAMP (8-pCPT-2'-O-Me cAMP), which selectively activate either PKA or EPAC, respectively. We show that in T cells, 6-Bnz-cAMP exerts similar globally inhibiting effects on cytokine secretion as 8-pCPT-cAMP, indicating that these effects are mediated by PKA. On the contrary, 8-pCPT-2'-O-Me-cAMP specifically inhibits the production of interleukin-10 (IL-10) in lipopolysaccharide-activated T-cell-depleted peripheral blood mononuclear cells, whereas the production of IL-1beta, tumor necrosis factor alpha, and IL-12 is not or hardly affected. Inhibition by 8-pCPT-2'-O-Me cAMP of IL-10 production was confirmed using purified monocytes. Further, in B cells 6-Bnz-cAMP, but not 8-pCPT-2'-O-Me-cAMP, stimulated IL-10 production. In conclusion, cAMP stimulates IL-10 production via PKA in activated B cells, but inhibits IL-10 production in activated monocytes through EPAC. We speculate that selective effects of PKA and EPAC on cytokine production in leukocyte subsets open up therapeutic possibilities using selective activators or inhibitors of EPAC or PKA. PMID- 20586616 TI - American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). AB - PURPOSE: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. RESULTS: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria. RECOMMENDATIONS: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials. PMID- 20586617 TI - TMPRSS2:ERG fusion gene and androgen-ablation therapy in prostate cancer. PMID- 20586618 TI - Critical diagnoses in anatomic pathology. PMID- 20586621 TI - Effectiveness of the RhIg dose calculator. PMID- 20586622 TI - Preparation of immunohistochemical control from Helicobacter pylori culture. PMID- 20586623 TI - Adequacy of surgical pathology reporting of cancer: a College of American Pathologists Q-Probes study of 86 institutions. AB - CONTEXT: Inclusion of all scientifically validated elements in surgical pathology cancer reports is needed for optimal patient care. OBJECTIVE: To evaluate the frequency with which surgical pathology cancer reports contain all the scientifically validated elements required by the American College of Surgery (ACS) Commission on Cancer (CoC), the extent to which checklists are used, and the effects that the use of checklists have on the completeness of cancer reports. DESIGN: Participants in the College of American Pathologists voluntary Q Probes program reviewed 25 consecutive surgical pathology reports to include cancer reports from breast, colon, rectum, and prostate cancer specimens. For each report, the type and total number of missing required elements, deemed essential by the ACS CoC, was recorded. RESULTS: A total of 2125 cancer reports were reviewed in 86 institutions; 68.8% of all surgical pathology cancer reports included all the required elements. Institutions in which checklists were routinely used reported all required elements at a higher rate than those that did not use checklists (88% versus 34%), and institutions that had a system in place to track errors also reported all required elements at a higher rate when compared to those that did not have such a system in place (88% versus 68%). The missing mandated elements, common to cancer reports of all tumor types, were extent of invasion and status of the resection margin. CONCLUSIONS: This study demonstrates that about 30% of cancer reports do not have all the scientifically validated elements required by the ACS CoC. Pathology departments in which checklists are not routinely used have a substantially lower rate of reports that include all the required elements. PMID- 20586624 TI - Proficiency survey-based evaluation of clinical total and allergen-specific IgE assay performance. AB - CONTEXT: The diagnostic algorithm for human allergic disease involves confirmation of sensitization by detection of allergen-specific immunoglobulin E (IgE) antibody in individuals suspected of having allergic disease because of a history of allergic symptoms after known allergen exposure. Previous studies showed wide disparity among clinically reported allergen-specific IgE levels from different serologic assays. OBJECTIVE: To validate the relative analytic performance (sensitivity, interassay reproducibility, linearity/parallelism, intermethod agreement) of clinically used total and allergen-specific IgE assays by using College of American Pathologists' Diagnostic Allergy "SE" Proficiency Survey data. DESIGN: Data from 2 SE survey cycles were used to assess relative analytic performance of the ImmunoCAP (Phadia), Immulite (Siemens Healthcare Diagnostics), and HYTEC 288 (HYCOR-Agilent Technologies) total and allergen specific IgE assays. In each cycle, 2 recalcified plasma pools from atopic donors were diluted twice with IgE-negative serum and evaluated in approximately 200 federally certified clinical laboratories for total IgE and IgE antibody to 5 allergen specificities. Statistical analysis evaluated analytic sensitivity, linearity, reproducibility, and intermethod agreement. RESULTS: Interlaboratory intramethod, intermethod, and interdilution agreement of all 6 clinically used total serum IgE assays were excellent, with coefficients of variation (CVs) below 15%. Interlaboratory intramethod, and interdilution agreement of 3 clinically used allergen-specific IgE assays were also excellent with CVs below 15%. However, intermethod CVs identified between-assay disagreement greater than 20% in 80% of allergen-specific IgE measurements. Allergen reagents and patients' immune response heterogeneity are suggested probable causes. CONCLUSIONS: Clinical total and allergen-specific IgE assays display excellent analytic sensitivity, precision, reproducibility, and linearity. Marked variability in quantitative estimates of allergen-specific IgE from clinically used automated immunoassays is a concern that may be ameliorated with component allergen use. PMID- 20586625 TI - Diagnostic utility of P504S/p63 cocktail, prostate-specific antigen, and prostatic acid phosphatase in verifying prostatic carcinoma involvement in seminal vesicles: a study of 57 cases of radical prostatectomy specimens of pathologic stage pT3b. AB - CONTEXT: Seminal vesicle invasion by prostatic carcinoma is directly associated with tumor staging; verification is challenging when the tumor demonstrates cribriform or papillary growth patterns or there are back-to-back small-gland proliferations. P504S is overexpressed in prostatic carcinoma and high-grade prostatic intraepithelial neoplasia with cytoplasmic immunoreactivity. p63 has positive immunoreactivity in basal cell nuclei of benign prostatic glands. Many researchers use a combination of these antibodies and their different colors. OBJECTIVE: To evaluate the usefulness of a single-color P504S/p63 cocktail immunostain in verifying prostatic carcinoma within the seminal vesicle. DESIGN: Sections from 57 radical prostatectomy specimens of pathologic stage pT3b that contain seminal vesicle with prostatic carcinoma involvement were immunostained with primary antibodies against prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) and a cocktail of antibodies against P504S and p63. RESULTS: Prostatic carcinoma cells from all 57 cases were diffusely positive for P504S, PSA, and PAP with cytoplasmic staining and no p63 nuclear staining. Seminal vesicle epithelium from all 57 cases was negative for all 3 markers with distinct p63 nuclear staining of the basal cells. Benign prostatic tissue was positive for PSA and PAP, as well as for p63, but negative for P504S. CONCLUSIONS: The P504S/p63 one-color cocktail is a practical and cost-effective stain to differentiate prostatic carcinoma that involves the seminal vesicle from seminal vesicle epithelium. It is superior to PSA or PAP when sections contain both seminal vesicle and benign glands because PSA and PAP cannot distinguish benign from malignant glands. PMID- 20586626 TI - Diagnosing placental membrane hypoxic lesions increases the sensitivity of placental examination. AB - CONTEXT: Two relatively unknown and recently described placental membrane hypoxic lesions (laminar necrosis and microscopic chorionic pseudocysts) have never been compared with time-honored, focal (infarction), and diffuse hypoxic lesions of placental parenchyma. OBJECTIVE: To compare the effect on placental diagnosis of the above placental membrane hypoxic lesions and chorionic disc hypoxic lesions (infarctions and global hypoxic pattern of placental injury). DESIGN: Twenty three clinical (maternal and fetal) and 32 gross and microscopic placental features were retrospectively compared in 4590 placentas from a placental database built during a 13-year period: 168 placentas with at least one hypoxic disc lesion (infarct or global hypoxia) and at least one membrane lesion (microscopic chorionic pseudocysts or laminar necrosis (group 1), 750 placentas with at least one hypoxic villous lesion but no membrane lesion (group 2), 480 placentas with at least one membrane lesion but no villous lesion (group 3), and 3192 placentas with no hypoxic villous or membrane lesions (group 4). RESULTS: Several clinical and fetal conditions and placental features known to be associated with in utero hypoxia had a statistically significant correlation with the index hypoxic placental lesions, both villous and membranous. Of placentas from patients associated with clinical conditions at risk for hypoxia, 15% featured only hypoxic membrane lesions without a chorionic disc hypoxic lesion. CONCLUSIONS: Recognizing placental membrane hypoxic lesions increases the sensitivity of placental examination in diagnosing placental hypoxia by at least 15%. The risk of in utero hypoxia is increased when microscopic chorionic pseudocysts and laminar necrosis occur in conjunction with villous hypoxic lesions. PMID- 20586627 TI - Clinicopathologic analysis of cutaneous lymphoma in taiwan: a high frequency of extranodal natural killer/t-cell lymphoma, nasal type, with an extremely poor prognosis. AB - CONTEXT: Primary cutaneous lymphoma is an uncommon, extranodal lymphoma, and it is usually more indolent with a better prognosis than its histologically similar systemic counterpart is. OBJECTIVES: To illustrate the clinicopathologic features of cutaneous lymphomas in Taiwan and to compare the relative frequencies of subtypes of cutaneous lymphoma among different geographic areas. DESIGN: A total of 56 patients with cutaneous lymphomas were retrospectively collected and were reclassified according to the 2005 World Health Organization and the European Organization for Research and Treatment of Cancer and the 2008 World Health Organization classifications. The data were compared with those from other studies for different geographic areas. RESULTS: Thirty-one (55%) tumors were primary cutaneous lymphomas, and twenty-five (45%) tumors were secondary or concurrent cutaneous lymphomas. Among primary cutaneous lymphomas, 23 cases (74%) were T-cell or natural killer-cell lymphomas, and 8 cases (26%) were B-cell lymphomas. The most common types were extranodal natural killer/T-cell lymphoma, nasal type, and primary cutaneous peripheral T-cell lymphoma, unspecified (5 cases each; 16%). In contrast with other primary cutaneous B-cell and T-cell lymphomas, either primary or secondary extranodal cutaneous natural killer/T-cell lymphomas, nasal type, had extremely poor prognoses (1-year overall survival, 0%). CONCLUSIONS: This study showed that the frequency of subtypes of primary cutaneous lymphoma varied in different geographic areas. Compared with the Western countries, there was a higher frequency of extranodal natural killer/T cell lymphoma, nasal type, and a lower frequency of mycosis fungoides in Taiwan. Extranodal natural killer/T-cell lymphoma, nasal type, also had an extremely poor prognosis compared with other lymphomas. PMID- 20586628 TI - Intraluminal polypoid metastasis of renal cell carcinoma in gallbladder mimicking gallbladder polyp. AB - CONTEXT: Metastatic renal cell carcinoma (RCC) in gallbladder is rare with only 18 cases published in the English literature. OBJECTIVES: To review the clinicopathologic characteristics of metastatic RCC in gallbladder and to correlate the findings with clinical outcomes. DESIGN: We report 4 additional cases of intraluminal polypoid metastasis of RCC in gallbladder and reviewed all reported cases, to our knowledge, of metastatic RCC in gallbladder in the English literature. RESULTS: Most of the patients (19 of 22; 86%) were men. The ages at presentation ranged from 39 to 84 years with a median age of 61.5 years. All cases showed an intraluminal polypoid/pedunculated mucosal mass mimicking a gallbladder polyp. Histologically, all cases were clear cell RCC with most of the tumors either confined to gallbladder mucosa (67%) or involved both mucosa and muscular layer (27%). The longest interval between nephrectomy and the development of gallbladder metastasis was 27 years. CONCLUSIONS: Metastatic clear cell RCC should be considered in the differential diagnosis of polypoid lesion of the gallbladder with clear cell morphology. Solitary metastasis of RCC in gallbladder correlated with better survival, and simple cholecystectomy for solitary metastatic RCC may provide patients with favorable long-term survival. PMID- 20586629 TI - Myelodysplastic syndromes arising in patients with germline TP53 mutation and Li Fraumeni syndrome. AB - CONTEXT: Li-Fraumeni syndrome (LFS), characterized by predisposition to early onset of a variety of malignancies, is usually associated with germline mutation of the tumor-suppressor gene, TP53. Mutation carriers are at increased risk of multiple primary tumors, many of which arise in previous radiation-therapy sites. In patients with LFS, acute myeloid leukemia is uncommon and myelodysplastic syndrome (MDS) is rare. OBJECTIVE: To evaluate the morphologic, cytogenetic, and molecular diagnostic findings of 3 unique cases of MDS arising in patients with germline TP53 mutation, 2 with classic LFS. DESIGN: We searched the Li-Fraumeni Syndrome Registry in the Department of Genetics at the University of Texas M. D. Anderson Cancer Center (Houston, Texas) and identified 3 patients with documented germline TP53 mutations or LFS who had developed MDS during a period of 6 years (2000-2005). The clinical, cytogenetic, and molecular diagnostic data and bone marrow aspirate smears and biopsies on all patients were reviewed. Immunohistochemical staining with antibody to p53 was also performed. RESULTS: Two patients met the criteria for classic LFS; one had no history of malignancy in first-degree relatives. The MDS followed chemotherapy and radiation therapy and progressed to acute myeloid leukemia in 2 patients. Cytogenetic analysis demonstrated chromosome 5 abnormalities in a complex karyotype in all cases. Two patients died, one of acute myeloid leukemia and one with glioblastoma multiforme, MDS, and persistent pancytopenia. CONCLUSIONS: Patients with LFS may develop MDS, which is most likely therapy-related and is associated with cytogenetic markers of poor prognosis. PMID- 20586630 TI - Limiting the use of atypical/inconclusive as a category in nongynecologic cytology specimens. AB - CONTEXT: 'Atypical' has served as a descriptive term in cytology since the birth of the specialty by Dr Papanicolaou. This indeterminate diagnosis often results in repeat biopsies or additional tissue sampling and a needless delay in patient care if used inappropriately. Because of the definitional ambiguity of this term and the associated physician frustration, we have made a concerted effort at Methodist Hospital since 1995 to minimize the use of 'atypical' as a diagnostic category. OBJECTIVE: To evaluate whether the dissolution of the 'atypical' category has increased our cytologic-histologic discordance rate to more than the published reference range. DESIGN: From March 3, 2006, through December 31, 2008, all nongynecologic cases with 'atypical/indeterminate' listed as the general diagnostic category were identified and retrieved from our laboratory data files. We then assessed the cytologic-histologic correlation rate during the corresponding time frame. RESULTS: A total of 48 'atypical' cases (0.2%) from 19 347 nongynecologic specimens were identified. Of the 'atypical' cases, 52% (25 of 48) had intradepartmental consultation, 58% (28 of 48) had additional preparations examined, and 29% (14 of 48) documented limitations because of poor preservation. Our cytologic-histologic discrepancy rate for the period was 5.5% (214 of 3912 cases), with 89.3% (191 of 214 cases) resulting from sampling issues. On review of the small percentage of cytologic interpretative discrepancies, only one case was unhampered by less than 10% tumor cellularity or poor preservation. CONCLUSIONS: Not using 'atypical' as a diagnostic category, unless defined by Bethesda guidelines, has not affected our cytologic-histologic correlation rate. PMID- 20586631 TI - Ovarian frozen section diagnosis: use of whole-slide imaging shows excellent correlation between virtual slide and original interpretations in a large series of cases. AB - CONTEXT: Whole-slide images (WSI) are a tool for remote interpretation, archiving, and teaching. Ovarian frozen sections (FS) are common and hence determination of the operating characteristics of the interpretation of these specimens using WSI is important. OBJECTIVES: To test the reproducibility and accuracy of ovarian FS interpretation using WSI, as compared with routine analog interpretation, to understand the technology limits and unique interpretive pitfalls. DESIGN: A sequential series of ovarian FS slides, representative of routine practice, were converted to WSI. Whole-slide images were examined by 2 pathologists, masked to all prior results. Correlation characteristics among the WSI, the original, and the final interpretations were analyzed. RESULTS: A total of 52 cases, consisting of 71 FS slides, were included; 34 cases (65%) were benign, and 18 cases (35%) were malignant, borderline, and of uncertain potential (9 [17%], 7 [13%], and 2 [4%] of 52 cases, respectively). The correlation between WSI and FS interpretations was 96% (50 of 52) for each pathologist for benign versus malignant, borderline, and uncertain entities. Each pathologist undercalled 2 borderline malignant cases (4%) as benign cysts on WSI. There were no overcalls of benign cases. Specific issues within the benign and malignant groups involved endometriosis versus hemorrhagic corpora lutea, and granulosa cell tumor versus carcinoma, respectively. CONCLUSIONS: The correlation between original FS and WSI interpretations was very high. The few discordant cases represent recognized differential diagnostic issues. Ability to examine gross pathology and real-time consultation with surgeons might be expected to improve performance. Ovarian FS diagnosis by WSI is accurate and reproducible, and thus, remote interpretation, teaching, and digital archiving of ovarian FS specimens by this method can be reliable. PMID- 20586632 TI - Lobular carcinoma in situ variants in breast cores: potential for misdiagnosis, upgrade rates at surgical excision, and practical implications. AB - CONTEXT: Differentiating ductal carcinoma in situ (DCIS) from lobular carcinoma in situ (LCIS) on core biopsy has important clinical implications. Lobular carcinoma in situ variants, including LCIS with necrosis and pleomorphic LCIS, share morphologic features with solid DCIS that may lead to misclassification. OBJECTIVES: (1) To review all LCIS variants diagnosed in core biopsies at Northwestern University, Feinberg School of Medicine, and determine the frequency of misinterpretation of variant LCIS as solid DCIS in archival core biopsies, and (2) to determine the frequency of upgrade to invasive carcinoma or DCIS in the surgical excision. DESIGN: Consecutive core biopsies with original diagnoses of predominantly solid DCIS without invasion that were performed between January 2001 and December 2005 at Northwestern University, Feinberg School of Medicine, were selected for E-cadherin staining. The revised diagnosis of LCIS was based on E-cadherin negativity and morphology. The frequency of LCIS variants upgraded was then estimated from all core biopsies with original or revised diagnoses of pleomorphic LCIS or LCIS with necrosis. RESULTS: Among 75 cases of solid DCIS, 10 (13.3%) were reclassified as LCIS, including 9 variants (5 pleomorphic LCIS, 4 LCIS with necrosis) and 1 classic LCIS. Twenty-eight patients comprised the entire group of LCIS variant cases (both reclassified and originally diagnosed cases). Seven patients with LCIS variants (25%) were upgraded to invasive lobular carcinoma in surgical excision (4 of 11 cases of LCIS with necrosis [36%] versus 3 of 17 cases of pleomorphic LCIS [18%]). CONCLUSIONS: About one-tenth of solid DCIS diagnosed in core biopsies in the past may represent LCIS variants. These show a 25% upgrade to invasive lobular carcinoma in surgical excision. The distinction of an LCIS variant from DCIS is important because of its implications for radiation therapy, although it may not affect surgical management. PMID- 20586633 TI - Legal aspects of laboratory medicine and pathology for residents and fellows: a curriculum for pathology training programs. AB - CONTEXT: Preparing residents and fellows to manage laboratories and pathology practices increasingly requires awareness of the law and a framework within which to manage legal risk in dealing with compliance, malpractice, and human resources issues. OBJECTIVES: To describe a curriculum for pathology and laboratory medicine residents and fellows that highlights activities most likely to result in adverse legal outcomes and to help trainees understand when the services of an attorney may be required. DESIGN: The 3-hour course evolved as part of a comprehensive leadership and management curriculum designed to help meet systems based practice and professionalism requirements. Didactic lectures and interactive case scenarios were presented, and participants then evaluated the course content and speakers on a 5-point scale (5 = high). Short-term knowledge accumulation was assessed by comparison of performance on the laboratory administration section of the Resident In-Service Examination between junior residents who had not taken the course and senior residents who did take the course. RESULTS: The course was evaluated by 72 trainees during a 5-year period (2004-2008); the mean overall rating was 4.6 (range, 3.5-5.0). Senior residents (n = 37) had a mean (SD) score on the Resident In-Service Examination laboratory administration section of 521 (67) for 2004 through 2008. Junior residents (n = 51), who had not yet completed the course, scored 470 (70) (P < .001) for the same period. CONCLUSIONS: This curriculum met the needs of professionals entering careers in laboratory medicine and pathology and can be modified for other pathology and laboratory medicine training programs. PMID- 20586634 TI - The concentration of CD44 is increased in hematopoietic stem cell grafts of patients with acute myeloid leukemia, plasma cell myeloma, and non-Hodgkin lymphoma. AB - CONTEXT: In autologous hematopoietic stem cell transplantation (autoHSCT), malignant cells remaining in the graft may re-engraft leading to relapse of the original disease. CD44 is known to play a role in the engraftment of leukemia initiating cells and is shed from the surface of malignant cells. Soluble CD44 is a cleaved fragment, which is found in the serum of patients with metastasized epithelial and hematologic malignancies and in some other cancers, and has been demonstrated to be correlated with clinical outcome. OBJECTIVES: To investigate (1) a possible correlation between the concentration of CD44 in an autoHSCT graft and the type of hematologic malignancy and (2) a possible correlation between the concentration of CD44 in the autoHSCT graft with clinical outcome after autoHSCT. DESIGN: We measured CD44 in 157 hematopoietic stem cell grafts from patients with hematologic malignancies and from 43 healthy donors by enzyme-linked immunosorbent assay. RESULTS: Levels of CD44 were almost 2-fold higher in the patients' grafts. Highest levels were found in the grafts of patients with acute myeloid leukemia, diffuse large B-cell lymphoma, and plasma cell myeloma, congruent with known CD44 expression levels in these malignancies. The survival advantage among patients with CD44 levels less than 22 000 ng/mL was highly statistically significant. CONCLUSION: These results show that CD44 levels in an autoHSCT graft may be linked to clinical outcome after autoHSCT. PMID- 20586635 TI - Cardiac sarcoidosis: a pathology-focused review. AB - CONTEXT: Sarcoidosis is a granulomatous disease of unclear etiology. It is not commonly fatal, but when sarcoidosis is fatal, it is most often from cardiac involvement and when sarcoidosis involves the heart, it frequently causes death. The disease presents diagnostic challenges both clinically and histologically. OBJECTIVES: To review the histology of cardiac sarcoidosis and the histologic differential diagnosis of cardiac granulomatous disease and to review the epidemiology and gross pathology of cardiac sarcoid as well as discuss current controversies, clinical diagnostic criteria, and proposed mechanisms of pathogenesis. DATA SOURCES: We reviewed the literature searchable on PubMed as well as selected older studies revealed by our review of the recent literature. Photographs were taken from cases on file at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) and Columbia University Medical Center (New York, New York). CONCLUSIONS: Sarcoidosis is a focal or disseminated granulomatous disease that likely represents the final common pathway of various pathogenic insults in a genetically susceptible host. The type of insult may influence the specific sarcoid phenotype. Controversy still abounds, but many areas of investigation around sarcoidosis are yielding exciting discoveries and bringing us closer to a richer understanding of this puzzling disease. PMID- 20586636 TI - The use of autopsy in preclinical medical education: a survey of pathology educators. AB - CONTEXT: Declining rates and increased competition for student contact hours pose challenges to integrating autopsies into preclinical curricula. Some have stated that the practice is minimally used with few students having the opportunity to observe necropsies. OBJECTIVE: To determine the degree to and manner in which autopsies are used in the preclinical medical education. DESIGN: A survey was distributed to the membership of the Group for Research in Pathology Education, an organization of preclinical pathology educators, assessing the nature of preclinical student exposure to postmortem examinations, how the experience was integrated in curricula, and attitudes toward the practice. RESULTS: Fifty-one of 131 instructors (38.9%) responded. Most (86.2%) integrated autopsy material into coursework, usually in pathology education (63.1%) with 10.7% using it in discussions on end-of-life issues. The majority (74.5%) furnish students the opportunity to observe autopsies, typically in small groups. Volume was the only variable significantly related to whether the opportunity was provided (P < .001). The experience was required in 56.3% of schools and usually less than 10% of students attended voluntarily. Although most educators felt it was important in general and pathology curricula, responses were mixed regarding autopsy's utility in discussions on death and dying. Common challenges were low autopsy numbers and busy class schedules. CONCLUSIONS: Most surveyed schools formally offer the opportunity to observe autopsies and incorporate autopsy themes in curricula. However, as only 41% of these institutions require the practice and most medical students did not view an autopsy voluntarily, less than half of preclinical students actually observe postmortem examinations. PMID- 20586637 TI - Implementation and assessment of a resident curriculum in evidence-based transfusion medicine. AB - CONTEXT: Given the number of controversial issues in transfusion medicine, an understanding of biostatistics and evidence-based medicine is invaluable. No detailed curricula that address teaching critical appraisal of the transfusion medicine literature have been published or evaluated. OBJECTIVE: To design, implement, and evaluate an evidence-based transfusion medicine curriculum. DESIGN: Four hour-long training sessions in journal club format were designed for a 2-month transfusion medicine rotation for clinical pathology residents. A previously validated survey was administered precurriculum and postcurriculum to gauge changes in resident self-reported attitudes and confidence regarding biostatistics methods and critical appraisal of the medical literature. Residents were also asked to evaluate the course regarding content, execution, and utility. RESULTS: Seven second-year residents participated in the sessions. Following the curriculum there were statistically significant increases in the residents' self reported ability to appraise critically and search the medical literature (P = .05). Resident confidence interpreting an article's statistical results also significantly improved (P = .01). There was also a significant change in the residents' desire to learn more about statistics (P = .02). Resident reviews of the curriculum were overall extremely positive. CONCLUSION: A 4-session curriculum can have a significant effect on resident self-reported ability to appraise critically and understand the medical literature and help foster interest in biostatistics. Although based on small numbers, this study represents one of the first efforts to evaluate the efficacy of a transfusion medicine curriculum and can potentially serve as a starting point to better integrate and evaluate knowledge of evidence-based transfusion medicine during residency training. PMID- 20586638 TI - Intrapulmonary ectopic liver after orthotopic heart transplantation. AB - We report a case of a 54-year-old woman who was found to have multiple intrapulmonary nodules detected on imaging 33 months after orthotopic heart transplantation. Needle biopsy of 2 discrete nodules showed benign hepatic tissue, consistent with intrapulmonary foci of ectopic liver. In this report, the clinical, radiologic, microscopic, and fluorescent in situ hybridization results of 2 biopsied nodules are described. A brief review of the published information on ectopic liver is also presented. To our knowledge, multiple ectopic foci of the liver have never been reported at any site. Furthermore, this is the first reported case that involves a transplant recipient, thereby introducing additional, unique ramifications to this rare but intriguing entity. PMID- 20586639 TI - Pituicytoma: characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization. AB - The pituicytoma is a rare neoplasm whose histogenesis is debated partly because of the diversity of tissue types present in the sellar region. In this article we illustrate the characteristic histologic, immunohistologic, and ultrastructural features of this unique neoplasm. Furthermore, we use array-based comparative genomic hybridization to demonstrate a unique pattern of genomic copy number aberrations in pituicytomas. Tumors were composed of bipolar, spindle cells that were immunopositive for S100, vimentin, and Bcl-2 and immunonegative for synaptophysin, chromogranin, and glial fibrillary acidic protein. Ultrastructural analysis was remarkable for absence of secretory granules. Array comparative genomic hybridization demonstrated genomic copy number imbalances, including losses on chromosome arms 1p, 14q, and 22q and gains on 5p. This pattern of genetic changes only partially overlaps with the genomic alterations reported in pituitary adenomas. In summary, our data suggest that pituicytomas are a unique subset of tumors of the sellar region. PMID- 20586640 TI - Pseudoangiomatous stromal hyperplasia: an overview. AB - Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign, proliferative mesenchymal lesion with possible hormonal etiology. It typically affects women in the reproductive age group. Pseudoangiomatous stromal hyperplasia is frequently an incidental histologic finding in breast biopsies performed for other benign or malignant lesions. Rarely, it can present as a firm, painless breast mass, which has been referred to as nodular or tumorous PASH. Grossly, tumorous PASH is a well-circumscribed, firm, rubbery mass with solid, homogenous, gray-white cut surface. On histologic examination, it is characterized by the presence of open slitlike spaces in dense collagenous stroma. The spaces are lined by a discontinuous layer of flat, spindle-shaped myofibroblasts with bland nuclei. The spindle cells express progesterone receptors and are positive for vimentin, actin, and CD34. The most important differential diagnosis on histopathology is angiosarcoma. Pseudoangiomatous stromal hyperplasia discovered incidentally does not require any additional specific treatment. Tumorous PASH is treated by local surgical excision with clear margins and the prognosis is excellent, with minimal risk of recurrence after adequate surgical excision. PMID- 20586641 TI - Well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts. AB - Primary, well-differentiated neuroendocrine (carcinoid) tumors of the extrahepatic biliary ducts are an uncommon cause of biliary obstruction. As compared to cholangiocarcinomas, which are more commonly seen at this location, these tumors tend to behave less aggressively, and only one-third metastasize. Tumor size (>2 cm) appears to be the best predictor of aggressive behavior. Surgery is the mainstay of treatment and complete resection offers prolonged disease-free survival. Accurate preoperative diagnosis is therefore important and can be made by examining brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasound-guided fine needle aspiration. It is important to keep this entity in mind, especially when examining cytologic or small biopsy specimens, so that appropriate immunohistochemical stains can be used to arrive at the correct diagnosis. PMID- 20586642 TI - Pancreatic manifestations of von Hippel-Lindau disease. AB - Von Hippel-Lindau disease is an uncommon, multisystem, multitumor disorder that can present in sporadic form but is more commonly inherited as an autosomal dominant disease with high penetrance. Affected patients are at increased risk for developing multiple synchronous or metachronous benign or malignant, cystic, and vascular neoplasms of various organs. The characteristic neoplasms associated with von Hippel-Lindau are hemangioblastoma of the central nervous system and retina, clear cell renal cell carcinoma, and pheochromocytoma, but other lesions are well recognized. Pancreatic lesions, both primary and metastatic, are common, and several differential diagnostic possibilities must be considered. PMID- 20586645 TI - Age-dependent denaturation of enzymes in the human lens: a paradigm for organismic aging? AB - Little is known about the rate of denaturation of proteins within the human body. To monitor this decline, human eye lenses were dissected into discrete regions that were formed at different stages of life and assayed for activity of lactate dehydrogenase (LDH) and a particularly stable enzyme, glutathione reductase (GR). Activity was highest for both enzymes in the most recently synthesized outer part of the lens, decreased further into the lens, and, for LDH, was barely detectable in nuclear regions that consist of proteins that were synthesized in utero. For LDH, 95% of total lens activity was found in the outer half of the adult lens at all ages. Activity was unchanged in the outermost part of the lens as a function of age, suggesting that the ability of humans to synthesize the two enzymes is not impaired, even up to the tenth decade. After age of 40, LDH activity declined steadily in the interior of the lens at the rate of 8.3% per decade. GR activity diminished more slowly, and western blotting indicated that both denaturation of the enzyme and truncation were responsible. These data support the view that few, if any, metabolic pathways remain in the center of older lenses. Exposure of the enzymes to physiological pH and temperature over a period of decades is presumably sufficient to cause denaturation. The center of older human lenses is a unique environment in which the accumulation of untoward posttranslational modifications to proteins can be studied in the absence of significant enzymatic amelioration. PMID- 20586644 TI - NT-020, a natural therapeutic approach to optimize spatial memory performance and increase neural progenitor cell proliferation and decrease inflammation in the aged rat. AB - The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT 020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche. PMID- 20586647 TI - Patterns of condom acquisition by condom-using men in the United States. AB - Condom-distribution programs have striven to make condoms more accessible to sexually active individuals, particularly adolescents and populations disproportionately affected by HIV and other STIs. Despite such programs, little is known about where condom-using men in the United States acquire their condoms. The purpose of this study was to document condom-access trends among a large sample of sexually active condom-using men in the United States. Data were collected from 1,832 men from all 50 U.S. states and the District of Columbia by using an Internet-based survey in which men provided details regarding the source of condoms that they had used within the past 30 days. Men reported acquiring their condoms from a variety of sources, including free condom-distribution programs (56.7%) and from venues where they had purchased condoms for themselves (75.7%). Bivariate analyses indicated that participants who reported using free condoms tended to be younger, self-identified as not heterosexual, or not currently in a monogamous relationship. Further, results indicated that those participants who accessed only free condoms did not differ from those who used only purchased condoms, indicating that perhaps efforts to make condoms more accessible through public health distribution campaigns are reaching a more general population of condom-using men than expected. Findings illustrate the importance of continuing free condom-distribution efforts but also suggest benefits of facilitating linkages between public health and a community's retail venues to increase access to the growing diversity of condoms in the marketplace. PMID- 20586648 TI - Efficacy of double-dose hepatitis B rescue vaccination in HIV-infected patients. AB - Impaired hepatitis B virus vaccine (HBVV) efficacy has been observed in HIV infected patients. We assessed the immunogenicity of double-dose (DD) hepatitis B virus revaccination in patients who had failed to respond to standard vaccination. A retrospective chart review of 4,663 patients ensued in two urban HIV clinics between January 2004 and March 2009. Of 363 patients who received three standard doses (SDs) of HBVV, 126 (34.7%) responded with detectable hepatitis B surface antibody [(HBsAb) HBsAb titer of > or =10 mIU/ml] and 237 (65.3%) nonresponders (NRs) remained seronegative. Among NRs, 61 received three to eight additional SDs of HBVV; 29 received three double doses (DDs) of HBVV (40 microg/dose), spaced at monthly dosing intervals; and 11 received from one to five additional SD HBVV (who remained seronegative) and then received three DDs HBVV. Response rate was significantly higher among the 40 DD recipients than among the 61 who received only additional SD (34/40, 85%, vs. 36/61, 59%; p = 0.006). In the revaccinated NR group (61 SD + 40 DD), a logistic regression analysis found that use of highly active antiretroviral therapy (HAART) (OR, 10.166; CI, 1.359-76.026; p = 0.024), and CD4 cell counts > or =200 cells/mm(3) at the time of revaccination (OR, 9.233; CI, 1.393-61.207; p = 0.021) were associated with HBsAb response, as was DD HBV revaccination (OR, 4.177; CI, 1.282 13.614; p = 0.018). Rescue DD hepatitis B vaccination appears to improve the HBsAb response rate significantly in HIV-infected NR patients, especially after an adequate immune restoration with HAART. More prospective studies are needed to confirm these findings. PMID- 20586646 TI - In-hospital death and adverse clinical events in elderly patients according to disease clustering: the REPOSI study. AB - OBJECTIVE: The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. METHOD: This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the effect of disease clusters on in-hospital death and adverse clinical events. RESULTS: A total of 86.7% of the patients were discharged, 8.3% were transferred to another hospital unit, and 5.0% died during hospitalization; 36.4% of the patients had at least one adverse clinical event. Patients affected by the clusters, including heart failure (HF) and either chronic renal failure (CRF) or chronic obstructive pulmonary disease, had a significant association with in-hospital death (OR, 4.3;95% confidence interval [CI], 1.6-11.5; OR, 2.9; 95% CI, 1.1-8.3, respectively), as well as patients affected by CRF and anemia (OR, 6.1; 95% CI, 2.3-16.2). The cluster including HF and CRF was also associated with adverse clinical events (OR, 3.5; 95% CI, 1.5-7.8). The effect of both HF and CRF and anemia and CRF on in-hospital death was additive. CONCLUSION: Several groups of older patients at risk of in-hospital death and adverse clinical events were identified according to disease clustering. Knowledge of the relationship among co-occurring diseases may help developing strategies to improve clinical practice and preventative interventions. PMID- 20586649 TI - Increase in use of vancomycin for Clostridium difficile infection in US hospitals. PMID- 20586650 TI - Observer bias in hand hygiene compliance reporting. AB - Differences in reported hand hygiene compliance rates were assessed on the basis of the unit affiliation of observers. In 2 hospitals, unit-based observers more often reported higher compliance rates than did non-unit-based observers (79% vs 58.6%; difference, 20.4%; P<.001). Nonstandardized data collection methods contribute to the variability in hand hygiene compliance rates. PMID- 20586651 TI - The burden of infectious gastroenteritis in elderly residents and staff of long term care facilities, Australia. AB - We estimated the incidence of gastroenteritis in 16 Australian long-term care facilities. During 12 months' surveillance, 245 (96%) of 254 episodes of gastroenteritis among long-term care residents were associated with 17 outbreaks in 11 facilities. Incidence in long-term care residents was 0.64 episodes per 1,000 bed-days (95% confidence interval, 0.29-1.42). PMID- 20586652 TI - Efficacy of alcohol-based hand rubs in the disinfection of stethoscopes. PMID- 20586653 TI - Predicting bacteremia among patients hospitalized for skin and skin-structure infections: derivation and validation of a risk score. AB - OBJECTIVE: Bacteremia is relatively common in patients with skin and skin structure infection (SSSI) severe enough to require hospitalization. We used selected demographic and clinical characteristics easily assessable at initial evaluation to develop a model for the early identification of patients with SSSI who are at higher risk for bacteremia. PARTICIPANTS: A large database of adults hospitalized with SSSI at 97 hospitals in the United States during the period from 2003 through 2007 and from whom blood samples were obtained for culture at admission. METHODS: We compared selected candidate predictor variables for patients shown to have bacteremia and patients with no demonstrated bacteremia. Using stepwise logistic regression to identify independent risk factors for bacteremia, we derived a model by using 75% of a randomly split cohort, converted the model coefficients into a risk score system, and then we validated it by using the remaining 25% of the cohort. RESULTS: Bacteremia was documented in 1,021 (11.7%) of the 8,747 eligible patients. Independent predictors of bacteremia (P<.001) were infected device or prosthesis, respiratory rate less than 10 or more than 29 breaths per minute, pulse rate less than 49 or more than 125 beats per minute, temperature less than 35.6 degrees C or at least 38.0 degrees C, white blood cell band percentage of 7% or more, white blood cell count greater than 11x10(9)/L, healthcare-associated infection, male sex, and older age. The bacteremia rates ranged from 3.7% (lowest decile) to 30.6% (highest decile) (P<.001). The model C statistic was 0.71; the Hosmer-Lemeshow test P value was .36, indicating excellent model calibration. CONCLUSIONS: Using data available at hospital admission, we developed a risk score that differentiated SSSI patients at low risk for bacteremia from patients at high risk. This score may help clinicians identify patients who require more intensive monitoring or antimicrobial regimens appropriate for treating bacteremia. PMID- 20586654 TI - Chlorhexidine use in the neonatal intensive care unit: results from a national survey. AB - Infection prevention guidelines do not endorse chlorhexidine gluconate (CHG) use in neonates who are less than 2 months old. A survey of US neonatology program directors revealed that most neonatal intensive care units use CHG, often with some restrictions. Prospective studies are needed to further address concerns regarding the safety of CHG in patients in the neonatal intensive care unit. PMID- 20586655 TI - Incidence of surgical site infection associated with robotic surgery. AB - OBJECTIVE: Robot-assisted surgery is minimally invasive and associated with less blood loss and shorter recovery time than open surgery. We aimed to determine the duration of robot-assisted surgical procedures and the incidence of postoperative surgical site infection (SSI) and to compare our data with the SSI incidence for open procedures according to national data. DESIGN: Retrospective cohort study. SETTING: A 689-bed academic medical center. PATIENTS: All patients who underwent a surgical procedure with use of a robotic surgical system during the period from 2000-2007. METHODS: SSIs were defined and procedure types were classified according to National Healthcare Safety Network criteria. National data for comparison were from 1992-2004. Because of small sample size, procedures were grouped according to surgical site or wound classification. RESULTS: Sixteen SSIs developed after 273 robot-assisted procedures (5.9%). The mean surgical duration was 333.6 minutes. Patients who developed SSI had longer mean surgical duration than did patients who did not (558 vs 318 minutes; P<.001). The prostate and genitourinary group had 5.74 SSIs per 100 robot-assisted procedures (95% confidence interval [CI], 2.81-11.37), compared with 0.85 SSIs per 100 open procedures from national data. The gynecologic group had 10.00 SSIs per 100 procedures (95% CI, 2.79-30.10), compared with 1.72 SSIs per 100 open procedures. The colon and herniorrhaphy groups had 33.33 SSIs per 100 procedures (95% CI, 9.68-70.00) and 37.50 SSIs per 100 procedures (95% CI, 13.68-69.43), respectively, compared with 5.88 and 1.62 SSIs per 100 open procedures from national data. Patients with a clean-contaminated wound developed 6.1 SSIs per 100 procedures (95% CI, 3.5-10.3), compared with 2.59 SSIs per 100 open procedures. No significant differences in SSI rates were found for other groups. CONCLUSIONS: Increased incidence of SSI after some types of robot-assisted surgery compared with traditional open surgery may be related to the learning curve associated with use of the robot. PMID- 20586656 TI - Increasing resources effected equity in access to revascularizations for patients with diabetes. AB - OBJECTIVES: To examine differences in access to coronary revascularization among a cohort of coronary patients with and without diabetes in 1995-2002 in Finland and to examine how rapidly increasing resources effected socioeconomic equity in access to these operations. DESIGN: An individual level nationwide register-based study of newly diagnosed CHD (coronary heart disease) patients (aged 40-79) in Finland. Rates for revascularizations were calculated per 1 000 person years. Socioeconomic differences were examined using Cox regression. RESULTS: Revascularization rates increased from 354 to 443 per 1 000 person years among men with CHD and from 301 to 366 among patients with diabetes. Among women with CHD the numbers were 224 and 249 and among patients with diabetes 208 and 325. Comparing trends for first revascularization between patient groups with and without diabetes differences increased somewhat among men. Among women, revascularization rates increased more among diabetic patients. Lower revascularization rates among lower socioeconomic groups were found throughout the study period in both patient groups. CONCLUSIONS: Simultaneously with large increase in cardiac operation rates, revascularization observed more common among women with diabetes compared to those without. However socioeconomic inequity in access to revascularizations among both genders remained even after increase in resources. PMID- 20586657 TI - Murine chronotoxicity to the antiallergic agent, cetirizine. AB - Cetirizine is a second-generation histamine H1-receptor antagonist used in the treatment of allergic diseases. The aim of the study was to assess whether cetirizine toxicity estimated by, for example, death, body loss, and leucopenia, is circadian rhythm dependent. A total of 210 male Swiss mice, aged 9 weeks, were synchronized for 3 weeks to 12-hour light (i.e., rest span)/12-hour dark (i.e., activity span) cycles. The drug was administered per os (orally). Each lethal (DL(50) = 750 mg/kg) and sublethal (DT(50) = 55 mg/kg) dose was administered to comparable groups of animals at six different circadian time points (1, 5, 9, 13, 17, and 21 hours after light onset; HALO). The death rate was dosing time dependent (P <0.001). Drug dosing at 5 HALO resulted in maximum mortality (76.75%), whereas dosing at 17 HALO resulted in the lowest mortality rate (16.7%). Cosinor analyses validated a statistically significant circadian rhythm in death rate (P < 0.008). Changes in body weight after cetirizine administration were dosing time dependent (P < 0.01), with the dosing time of least effect ( 0.7% loss) at 17 HALO and of greatest effect (-7% loss) at 5 HALO. Cosinor analyses validated a statistically significant circadian rhythm in body loss (P < 0.05). A statistically significant decrease in leukocyte number varied, according to antihistamine dosing time (P < 0.01), with the dosing time of least leucopenia (~-17%) at 17 HALO and of greatest leucopenia (~-28%) at 5 HALO. The results show that cetirizine dosing time at the midactivity (dark) span seems to be optimal, since it corresponds to the best tolerance. PMID- 20586658 TI - The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer. AB - PURPOSE: To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. MATERIAL AND METHODS: Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUV(max)) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The DeltaSUV(max) during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). RESULTS: DeltaSUV(max) during and after CRT significantly correlated with the pathological response to treatment (during CRT: DeltaSUV(max) = 59% +/- 12% for pCR vs. 25% +/- 27% if no pCR, p=0.0036; post-CRT: 90% +/- 11 for pCR vs. 63% +/- 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for DeltaSUV(max) of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 +/- 0.12 * 10(-3) mm(2)/s for pCR vs. 1.2 +/- 0.24 * 10(-3) mm(2)/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 * 10(-3) mm(2)/s. Combining the provided DeltaSUV(max) thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the DeltaSUV(max) during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). CONCLUSIONS: The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT. PMID- 20586659 TI - Psychological resilience and long-term distress in Swedish and Icelandic parents' adjustment to childhood cancer. AB - AIM: Studies of parental reactions to a child's cancer have traditionally been carried out within the framework of psychiatry and psychopathology. We studied the significance of individual resource factors strengthening parents' resilience to long-term cancer-related distress, a focus that has rarely been used. PARTICIPANTS AND METHODS: The two-nation Nordic sample included 398 parents; 190 of whom had experienced a child's cancer, and 208 reference parents. We studied the sense of coherence (SOC) using the SOC-13 questionnaire. For assessing distress reactions we used a primarily illness-specific 11-dimensional Parental Psychosocial Distress in Cancer (PPD-C) self-report questionnaire developed for use with parents of childhood cancer patients, and the General Health Questionnaire (GHQ). Resilience was defined as absence of/less severe distress. RESULTS: Low SOC was significantly associated with more severe distress in all dimensions of the PPD-C and GHQ. The protective effect of SOC was indicated by it being most negatively related to general psychiatric symptoms, physical and psychological stress symptoms, anxiety and depression. The influence of SOC varied with parents' gender, showing a stronger modifying influence among mothers. Mothers and fathers also differed in their utilisation of professional psychosocial support when confronted with the child's cancer. CONCLUSION: Parental resilience to cancer-related distress varies with identifiable strength factors. A strengths-oriented approach helps in understanding parental adjustment to childhood cancer. In order to counteract psychological vulnerability, addressing resilience instead of pathology helps to identify parents at risk and in need of professional support when faced with a child's cancer. PMID- 20586660 TI - Do we need fractionation-corrected doses in sequential two-phase treatments? A quantification of dose differences between non-corrected and corrected combined non-uniform dose distributions in normal tissue. AB - BACKGROUND: For many tumour sites, external beam radiation therapy (EBRT) is delivered with a sequential two-phase treatment regime. Yet, there is a lack of consensus of how to add two different non-uniform dose distributions in order to evaluate the late radiation effect for normal tissue. The purpose of this novel investigation is to quantify the dose differences between non-corrected and fractionation-corrected combined non-uniform dose distributions. MATERIAL AND METHODS: We used a model of an organ at risk (OAR) located in six different positions relative the treated volume giving 16 clinically representative two phase treatment situations (46 Gy + 22 Gy). The linear-quadratic model was applied to correct for fractionation effects in each voxel before the doses were added. Dose differences were quantified using mean and maximum doses with corresponding fractionation-corrected doses as reference. RESULTS: Non-corrected doses were higher than fractionation-corrected doses in all treatment situations (mean dose: p<0.001; maximum dose: p=0.003). With the OAR outside the treated volume, non-corrected doses were 3-6 Gy higher representing 10-50% of the reference dose (10-25 Gy); with the OAR included in the treated volume, 1-6 Gy higher representing 1-15% (30-60 Gy). Mean dose differences were generally larger than maximum dose differences. CONCLUSION: Substantial dose differences were present in all of the simulated treatment situations but more apparent when the OAR was located outside the treated volume in both phases. Our findings require verification in clinical cases but nevertheless indicate a need for fractionation corrected doses in two-phase treatments both in the daily clinical routine as well as in the modelling of late radiation effects. Our data suggest that adjusting for fractionation effects would lead to lower tolerance doses than currently suggested, in particular for OARs with parallel tissue architecture. PMID- 20586661 TI - Clinicians' use of guidelines as illustrated by curative treatment of prostate cancer at a comprehensive cancer center. AB - BACKGROUND: We studied compliance to guidelines of curative treatments in prostate cancer (PCa), which were of special interest due to recent introduction of new treatment technologies and the fact that there existed a real choice between surgery and radiotherapy. MATERIAL AND METHODS: We did retrospective analyses of guidelines adherence for all PCa patients receiving curative treatment at the Norwegian Radium Hospital from 2004 to 2007 after the introduction of robot-assisted prostatectomy and after-loading brachytherapy. The patients were classified into three groups in relation to guidelines: the accordance, accordance after discussion, and the deviance groups. In time Period I (2004-2005) the 2003 EAU guidelines were used and in Period II (2006-2007) in house guidelines with minor modifications of EAU were applied. RESULTS: During the observation period 859 patients had curative treatment for PCa, and 83% of the patients were treated according to guidelines. In the deviance group (N=146), 119 men (82%) got prostatectomy instead of radiotherapy. The reasons for deviation in the second period were age >65 years (N=70) and surgery in cases with T3 tumors (N=10), Gleason score >8 (N=13) and combinations (N=26). Deviances from guidelines in the radiotherapy group (N=27) mainly concerned patient selecting this treatment due to expectations of preserving sexuality and/or fertility. CONCLUSIONS: In spite of acceptable overall compliance to guidelines for curative PCa treatment, the proportion of non-adherence should not been overseen, in particular when new treatment technologies are introduced. Guidelines for PCa need to be monitored regularly, and the compliance to guidelines has to be assessed on a regular basis. Guidelines should avoid too strict criteria, particularly in relation to age. PMID- 20586662 TI - No correlation between mandibular and non-mandibular measurements in osteoporotic men. AB - BACKGROUND: Screening for low bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) has been the traditional method for determining osteoporosis. Panoramic radiography is widely used in dentistry. PURPOSE: To determine the relationships between the values of dental panoramic indices (the mental index (MI), antegonial index (AI), panoramic mandibular index (PMI)) and the values of skeletal BMD (femoral BMD (f-BMD), and vertebral BMD (v-BMD)) in 25 osteoporotic men. MATERIAL AND METHODS: In the panoramic radiographs obtained from a total of 25 male individuals with osteoporosis, the means were calculated for MI, AI, and PMI values measured in the right and left mandible. DXA measurements of the femur and lumbar vertebrae BMD were also calculated. The correlation between these variables was assessed. RESULTS: No correlation was found between the BMD values of the femur and lumbar vertebrae and values of MI, AI, and PMI. CONCLUSION: No significant correlation was found between the mandibular and non-mandibular measurements in men with osteoporosis. MI, AI, and PMI indices should not be used in the evaluation of the skeletal status, because they are not reliable tools in screening for osteoporosis. PMID- 20586663 TI - Postpartum endoanal ultrasound findings in primiparous women after vaginal delivery. AB - BACKGROUND: Natural childbirth is regarded as the most frequent cause of anal sphincter defects. The majority of obstetric injuries are detectable only by anal endosonography (AES), in from 6.8% to 35% of women after vaginal delivery. PURPOSE: To evaluate prospectively anal sphincters in primiparous women in the first days after delivery to estimate the prevalence of anal sphincter defects and to correlate selected risk factors with the recognized injuries. MATERIAL AND METHODS: A total of 112 consecutive primiparous women aged 19-40 years (mean 29.3 years) underwent three-dimensional (3D) AES with the use of a BK Medical scanner Profocus 2202 in the first weeks after delivery. RESULTS: Twelve tears (10.7%) in the perineum, including three extending to anal sphincters (2.6%) were found on AES. As many as 86 (76.8%) women had medio-lateral episiotomies due to the practice pattern in our hospital or as a consequence of obstetric factors. The statistical analysis did not prove a significant association between diagnosed injuries and episiotomy (P=0.73), nor a traumatic effect of epidural anesthesia, fetus head circumference > or =34 cm, or birth weight > or =3525 g. CONCLUSION: Anal sphincter tears following childbirth were found in only 2.6% of primiparous women, suggesting that vaginal delivery might not imply high risk of pelvic floor damage as has previously been assumed. The results do not confirm that medio lateral episiotomy is conducive to obstetric anal sphincter defects. PMID- 20586664 TI - Analysis of gelatin plasma substitutes in blood based on detection of hydroxyproline derivatives. AB - The gelatin plasma substitute is often polydisperse and heterogenous, making it difficult to determine the elimination rate and half-life in the body. In this study, one method was developed based on quantitative determination of hydroxyproline derivatives. Two plasma substitutes were prepared by succinylation and genipin-crosslinking, respectively. After transfusion, the blood samples were hydrolyzed and derivatized, and then analyzed by HPLC. A two-phase exponential association equation was used for fitting the time-concentration curves. The results indicated that this method could be used for quantitative determination of gelatin in blood, and the pharmacokinetic parameters such as elimination rate and half-life. PMID- 20586665 TI - Pretreatment before ischemia induction with polymerized human placenta hemoglobin (PolyPHb) attenuates ischemia/reperfusion injury-induced myocardial apoptosis. AB - This study was designed to investigate the influence of polymerized human placenta hemoglobin (PolyPHb) pretreatment on ischemia/reperfusion (I/R) injury induced myocardial apoptosis. Isolated Sprague-Dawley rat hearts were perfused by Langendorff model. After basal perfusion, hearts were arrested by St.Thomas' solution (STS) with (Pre-HBOC group) or without PolyPHb (STS group), then subjected to I/R injury. Our results showed that PolyPHb pretreatment greatly reduced the TUNEL-positive myocardial cells and decreased the caspase-3 activity and cleavage, which was further confirmed by the linear regression analysis. Therefore, PolyPHb pretreatment was beneficial to attenuation of myocardial apoptosis and provided protection to the heart against I/R injury. PMID- 20586666 TI - [Orientation of endoscopic images: rectification by gravity]. AB - A known problem in endoscopic surgery (especially with flexible video endoscopes) is the absence of a stable horizon in endoscopic images displayed on a monitor. With our "ENDOrientation" approach, image rectification, even in non-rigid endoscopic surgery (particularly NOTES), can be realized with a tiny MEMS tri axial inertial sensor placed on the tip of an endoscope. This sensor measures the impact of gravity on each of the three orthogonal accelerometer axes in real time. After an initial calibration and temporal filtering of these three data steams, the rotation angle of an endoscope can be estimated directly. The achievable sampling rate of the inertial sensor is above the usual endoscopic video frame rate of 25 Hz; the rotation accuracy is approximately one degree. The image rectification can be performed in real time by digitally rotating the endoscopic video signal. Improvements and benefits have been evaluated in animal studies: coordination and movement of different instruments was rated to be much more intuitive with a stable horizon on endoscopic images. The recorded time stamps and position tracks clearly support this observation. PMID- 20586667 TI - Modularity of a new cementless acetabular revision cup system based on research of the anatomic variability of the pelvis. AB - There is a growing need for specific revision implants to meet the increasing occurrence of failed total hip arthroplasties displaying massive deficiencies in acetabular bone stock. The developed acetabular revision cup presented in this study is aimed at individual patient solutions using a multi-axial and angular stable fixation peg as well as a modular adaptable lateral flap. To obtain an optimum implant design, a database of computed tomography scans of 69 patients' pelves was collected and computational reconstruction of the pelvic bone morphology was conducted. Based on the anatomic measurements, the direction of the fixation peg of the revision cup was evaluated using custom software and the geometry of the lateral flaps was evaluated using rapid prototyping models of the pelvis. Furthermore, we conducted preclinical examinations of the acetabular revision system with regard to the safety of the angular stable locking mechanism of the fixation pegs and the mechanical stability of the lateral flap. The dynamic tests showed no mechanical failure of the fixation peg and its angular stable connection using a cyclic maximum torque of 24.5 Nm for one million cycles. The lateral flap and its fixation showed no mechanical failure using a cyclic maximum torque of 28.4 Nm for two million cycles. In conclusion, a promising solution to satisfy the requirements for adequate anatomical fit in a wide range of acetabular defects is presented. PMID- 20586668 TI - Early lymphocyte reconstitution is associated with improved transplant outcome after cord blood transplantation. AB - BACKGROUND AIMS: Previous studies have shown that rapid recovery of the absolute lymphocyte count (ALC) is associated with improved transplant outcomes after related and unrelated donor allogeneic stem cell transplantation (allo-SCT). No consistent association has been reported between lymphocyte recovery and transplant outcome after cord blood transplantation (CBT). METHODS: We reviewed the records of 40 consecutive CBT patients at our institution to determine the impact of lymphocyte recovery on transplant outcome. RESULTS: The majority of patients (83%) received CBT for hematologic malignancies. Patients with ALC >=150/MUL at 30 days post-CBT had decreased non-relapse mortality (NRM) (P = 0.011) and improved survival (P = 0.013) compared with ALC <150/MUL. Patients with ALC <100/MUL at 30 days post-CBT had a significantly higher rate of graft failure than those with ALC >=100/MUL (four of 10 versus one of 29; P = 0.011). ALC was positively correlated with the nucleated cell dose and inversely correlated with the patient's age. There was no relationship between disease risk, type of conditioning regimen, anti-thymocyte globulin and number of cord units on ALC recovery. CONCLUSIONS: Our results indicate that ALC 30 days post CBT is a surrogate for engraftment, and that low ALC (<150/MUL) identifies an 'at risk' population of patients after CBT. Studies are needed to determine ways to increase ALC cell numbers post-CBT, including ex vivo-expanded natural killer cells using adoptive immunotherapy, which might improve outcome after CBT. PMID- 20586669 TI - Timed inhibition of p38MAPK directs accelerated differentiation of human embryonic stem cells into cardiomyocytes. AB - BACKGROUND AIMS: Heart failure therapy with human embryonic stem cell (hESC) derived cardiomyocytes (hCM) has been limited by the low rate of spontaneous hCM differentiation. As others have shown that p38 mitogen-activated protein kinase (p38MAPK) directs neurogenesis from mouse embryonic stem cells, we investigated whether the p38MAPK inhibitor, SB203580, might influence hCM differentiation. METHODS: We treated differentiating hESC with SB203580 at specific time-points, and used flow cytometry, immunocytochemistry, quantitative real-time (RT) polymerase chain reaction (PCR), teratoma formation and transmission electron microscopy to evaluate cardiomyocyte formation. RESULTS: We observed that the addition of inhibitor resulted in 2.1-fold enrichment of spontaneously beating human embryoid bodies (hEB) at 21 days of differentiation, and that 25% of treated cells expressed cardiac-specific alpha-myosin heavy chain. This effect was dependent on the stage of differentiation at which the inhibitor was introduced. Immunostaining and teratoma formation assays demonstrated that the inhibitor did not affect hESC pluripotency; however, treated hESC gave rise to hCM exhibiting increased expression of sarcomeric proteins, including cardiac troponin T, myosin light chain and alpha-myosin heavy chain. This was consistent with significantly increased numbers of myofibrillar bundles and the appearance of nascent Z-bodies at earlier time-points in treated hCM. Treated hEB also demonstrated a normal karyotype by array comparative genomic hybridization and viability in vivo following injection into mouse myocardium. CONCLUSIONS: These studies demonstrate that p38MAPK inhibition accelerates directed hCM differentiation from hESC, and that this effect is developmental stage-specific. The use of this inhibitor should improve our ability to generate hESC-derived hCM for cell-based therapy. PMID- 20586670 TI - Cellular transplants in amyotrophic lateral sclerosis patients: an observational study. AB - BACKGROUND AIMS: Cytotherapy is a promising option for neurodegenerative disease treatment. Because of the fatal prognosis and imperative need for effective treatment, amyotrophic lateral sclerosis (ALS) patients request this therapy before its effectiveness has been verified. The increase in clinics offering cytotherapies but providing little scientific information has prompted considerable medical tourism. We present an observational study of Spanish ALS patients receiving cytotherapy, analyzing the experiences arising from the treatment (TX) and considering two progression markers, FVC and ALSFRS-R. METHODS: Twelve ALS patients with a mean age of 48.6 years (SD 12.8) received cytotherapy 26.9 months (SD 15.8) after clinical onset. ALSFRS-R and FVC at TX were 32.3 (SD 6.8) and 63.4% (SD 15.3), respectively. TX involved transplants of olfactory ensheathing cells in three patients, and autologous mesenchymal stromal cells in the remainder. RESULTS: One patient died 33 months post-TX after surviving for 49 months. Five required mechanical non-invasive home ventilation 7.4 months post-TX. Two required invasive ventilation 13 months post-TX. Five patients needed gastrostomy feeding 23.3 months post-TX. Survival between clinical onset and the study end date was 50 months (SD 17.2). No significant adverse events or changes in the decline of FVC and ALSFRS-R compared with the disease's natural history were observed. CONCLUSIONS: Our observations suggest that these therapies do not halt the course of the disease. Cytotherapy cannot yet be considered a curative treatment for ALS. PMID- 20586671 TI - Tuberculosis in HIV voluntary counselling and testing centres in Dar es Salaam, Tanzania. AB - The human immunodeficiency virus (HIV) has contributed to an increase in tuberculosis (TB) worldwide. HIV voluntary counselling and testing (VCT) centres are cost-effective for HIV screening. Therefore there is a potential of tapping into the success of VCT centres by incorporating TB screening. The aim of this study was to determine the extent of TB and TB/HIV co-infection among VCT centre attendees. We enrolled 1318 consecutive subjects from 2 VCT centres in Dar es Salaam. The diagnosis of TB was based on evidence of Mycobacterium tuberculosis in sputum or tissue aspirates following microscopy or culture. In the absence of M. tuberculosis, the presence of 2 of the following was considered: clinical features of TB, suggestive chest radiographs and response to anti-tuberculosis trial therapy. HIV was diagnosed in 347 (26%) subjects. TB was present in 101 (7.7%) subjects of whom 63 (62%) were diagnosed at VCT centres and 38 (38%) were known TB cases who came for HIV testing. Pulmonary TB (PTB) was detected in 52 (83%) subjects. The diagnosis of PTB was based on sputum culture in 35 (67%), sputum microscopy in 20 (38%), and clinical and radiological findings in 17 (33%) subjects. TB/HIV co-infection was detected in 70 (5.3%) subjects. PTB was common in stand-alone VCT centres. Therefore VCT centres could serve as an entry point for TB screening. PMID- 20586672 TI - Mast cell density and angiogenesis in oral dysplastic epithelium and low- and high-grade oral squamous cell carcinoma. AB - OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the 10 most common malignant tumors and SCC accounts for approximately 94% of all oral malignancies. The risk of malignant transformation in dysplastic lesions is greater than that of normal oral mucosa. The definite roles of mast cells and angiogenesis in OSCC have been under debate. The aim of this study was to compare mast cell count (MCC) and microvessel density (MVD) among normal oral mucosa, oral dysplastic epithelium and low- and high- grade OSCC. MATERIAL AND METHODS: A total of 42 specimens of OSCC (21 high- and 21 low-grade) were collected, along with six normal and 22 dysplastic oral mucosa. The mean MCC and MVD, as well as the correlation between them, were evaluated by immunohistochemical staining. RESULTS: Statistically significant increases in mean MCC and MVD were observed between normal oral mucosa and epithelial dysplasia, normal oral mucosa and OSCC and epithelial dysplasia and OSCC (P < 0.05), but there were no statistically significant differences in MCC and MVD between low- and high-grade OSCC. Also, the Spearman's correlation coefficient showed a significant correlation between MCC and MVD (r = 0.727, P < 0.001). CONCLUSIONS: The significant correlation found between MCC and MVD is in agreement with the idea that mast cells promote tumor progression via upregulation of angiogenesis. MCC and the degree of angiogenesis can potentially be used as indicators of the evolution of SCC from epithelial dysplasia. PMID- 20586673 TI - Degenerative changes in human temporomandibular joints in relation to occlusal support. AB - OBJECTIVE: Controversy exists concerning the etiological factors behind degenerative changes in the temporomandibular joints (TMJs). Tooth attrition, occlusal support, food consistency, ageing, gender and genetics are some possible causative factors that have been discussed in the literature. The aim of this study was to examine contemporary human skull material for possible relations between degenerative form and surface changes in the TMJs in relation to occlusal support. MATERIAL AND METHODS: The material consisted of 259 human skulls from 170 males and 89 females, with an age range of 18-100 years. RESULTS: Dental status was in general poor, and 22% of skulls were edentulous. Form and surface changes of both the condyles and the temporal components were more common in the present material compared to that in most previous studies. In males, irrespective of age, only weak and clinically insignificant correlations could be found between degenerative TMJ changes and occlusal support. In women, however, the correlations between these variables were in general much stronger, especially at higher ages. CONCLUSIONS: The present findings do not lend support to the hypothesis that loss of occlusal support is a causative factor for degenerative changes in the TMJs in male subjects. In women, such a correlation was obvious in the present sample, at least at higher ages. It can be speculated that hormonal factors play a role in the sex difference found. PMID- 20586674 TI - Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole treated mouse olfactory epithelium. AB - CONCLUSION: It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory-trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons. OBJECTIVE: Expression of TRPV1-4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed. METHODS: The localization of TRPV1 4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry. RESULTS: Normal OE showed a positive immunofluorescent reaction to TRPV1-4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment. PMID- 20586675 TI - Remote fitting in Nucleus cochlear implant recipients. AB - CONCLUSION: Remote programming is a viable alternative to face-to-face programming. The procedure can be regarded as safe, time and cost saving, and clinically feasible. OBJECTIVES: The aim of this study was to determine the suitability of commercially available video conferencing technology and remote control software for remote programming of sound processors in Nucleus cochlear implant recipients by assessing the feasibility, efficiency, risks, and benefits of remote programming compared to face-to-face programming. METHODS: This was a randomized, prospective study. Seventy Nucleus implant recipients were recruited for a random sequence comparison of one remote and one local programming session each. The time required for local or remote programming was measured and resulting MAP T and C levels were compared. The recipient provided feedback on the local and remote programming session. The audiologist and monitoring clinician were asked for their feedback on remote programming. RESULTS: Remote programming sessions were successfully finished for 69 recipients. No significant differences between T and C levels obtained by local and remote programming were found. The audiologists and monitoring clinicians agreed that the remote programming system provided an acceptable level of performance after most sessions. More than 50 participating recipients considered remote programming an efficient alternative to face-to-face-programming. PMID- 20586676 TI - First experiences with a new adjustable length titanium ossicular prosthesis (ALTO). AB - CONCLUSIONS: The new length-adjustable titanium prosthesis can give good results in terms of hearing results in ossiculoplasty. The possibility to readjust the length intraoperatively was seen as a good feature. OBJECTIVE: Hearing results of ossiculoplasty with a newly designed prosthesis in 14 patients were evaluated. The prosthesis is designed to allow adjustment of length in situ. METHODS: A retrospective pilot study was carried out, comparing the preoperative and postoperative audiological and clinical results with an age- and pathology matched group. The setting was the Department of Otolaryngology at the University of Heidelberg Medical Center, a tertiary referral center. In all, 14 patients underwent tympano-ossiculoplasty in which autologous reconstruction was not an option. The ossiculoplasty was performed as a therapeutic measure with the new titanium prosthesis. We evaluated the air-bone gap closure as established from preoperative and postoperative audiograms. We also looked at the clinical aspect of the tympanic membrane. RESULTS: The average air-bone gap came to a closure within 15 dB in 43% of the cases (6 of 14 patients). No re-perforations or extrusions of the prostheses were observed. PMID- 20586677 TI - Substance abusing mothers in residential treatment with their babies: postnatal psychiatric symptomatology and its association with mother-child relationship and later need for child protection actions. AB - BACKGROUND: A residential treatment model has been developed in Finland, which is specifically designed for substance abusing pregnant and parenting women, and has its focus on supporting both maternal abstinence from substances and mother-baby relationship. AIMS: Among mother-baby pairs in this residential treatment, to explore amount and type of maternal postnatal psychiatric symptoms, relationship with the baby, and their association with later need for child substitution care placements. METHODS: Participants were 34 mother-baby pairs from three units during pre- to postnatal period. Methods included self-report questionnaires for substance abuse and background data (pregnancy and perinatal period), experienced difficulties with the baby (1 month postnatally); maternal psychiatric symptoms (Brief Symptom Inventory, Edinburgh Pre-postnatal Depression Screen, Inventory of Interpersonal Problems; (pregnancy and 3 months) postnatally; videotaped mother child interaction measure (Care Index for infants and toddlers) and standardized test of child development (Bayley Scales of Infant Development) (4 months postnatally); questionnaire for follow-up information (2 years of child's age). RESULTS: Mothers showed high levels of different types of psychiatric symptomatology. Maternal interaction with the baby was on average weak, as 53% were within the high-risk range regarding sensitivity. Experiencing more difficulties in early care-giving of the baby was associated with higher amount of postnatal psychiatric symptomatology. Specific psychiatric symptoms were associated with later need for child substitution care. CONCLUSIONS: In designing treatment and follow-up of these mother-baby pairs, careful attention should be paid to pre- and perinatal identification and type of maternal psychiatric symptoms, and mothers' expressions of subjectively experienced difficulties in early care-giving of the baby. PMID- 20586678 TI - Cytokine profile and cytotoxicity in response to acute intratracheal dose of Metarhizium anisopliae in BALB/c mice. AB - Metarhizium anisopliae has been considered neither pathogenic nor toxic to mammals. However, some recent reports demonstrate that it is capable of causing infections in mammals including humans. Therefore, there is an urgent need to investigate the nature of infections this fungus induces in these animals. We therefore investigated the immunological and cytotoxic responses to acute intratracheal dose (10(8) conidia/50 MUl) of crude conidial suspension (CCS) of M. anisopliae (ARSEF 7487) in BALB/c mice. The secretion of proinflammatory cytokine IL-6 significantly increased at all the evaluated time points post infection. The titers of IFN-gamma, TNF-alpha, IL-12/IL-23-total p40 and IL-12 p70 showed continuous increasing trends from 6 h post infection (h PI) onwards and increased significantly at 24 h PI. While IL-10 activity was almost constant throughout the observation period, the IL-4 activity first increased at 6 h PI, beyond which it continuously decreased at the evaluated periods of time. The lactate dehydrogenase (LDH) and total protein levels increased significantly at the evaluated h PI. Collectively, the cytokine data suggested that the activation of IL-23/Th17 pathways leading to uncontrolled Th1 type response (elevated production of TNF-alpha, IFN-gamma and IL-6) in the early hours of infection contributed to neutrophilia and tissue damage. On the other hand significantly elevated levels of total protein, LDH and albumin indicated cytotoxicity. PMID- 20586679 TI - Microsatellite analysis and susceptibility to FCZ of Candida glabrata invasive isolates in Sfax Hospital, Tunisia. AB - We have noted that, during the last few years, there has been a redistribution of the most common Candida species with an increase in non-C. albicans Candida species, particularly Candida glabrata. In many countries, the high frequency of Candida glabrata shows the highest resistance rates. The main objective of this investigation was to analyze the genotypic variability of invasive C. glabrata isolates recovered over a period of six years and assess their in vitro susceptibility to fluconazole to determine the possible existence of relationships between genotype and susceptibility. We collected 50 invasive C. glabrata isolates (21.4%) from January 2001 to December 2007. The in vitro susceptibility profiles as determined by the E-test method showed that 8.3% of the isolates were resistant to fluconazole. The typing with three microsatellite markers RPM2, MTI and ERG3 demonstrated 12 multilocus genotypes distributed irregularly with a predominance of G1 (38%). A cluster (G9) was found among isolates collected in the same ward, at the same time period, suggesting cross transmission. Eleven of 13 patients who had previously been colonized by C. glabrata, were infected by their colonizing strains. However, we noted after prolonged treatment with fluconazole that there was an increase of the MIC for an isolate from one patient and in another patient, the selection of a more resistant variant. In our study, we didn't find an association between genotype and susceptibility to fluconazole. In conclusion, the predominance of some genotypes could be explained by nosocomial transmission or a selective ecological advantage rather than an emergence of a resistant isolate. PMID- 20586682 TI - Differential diagnosis of depressive illness versus intense normal sadness: how significant is the 'clinical significance criterion' for major depression? PMID- 20586680 TI - Adoptive antifungal T cell immunotherapy--into the clinic? AB - The morbidity and mortality rates of invasive fungal infection in allogeneic stem cell recipients are still unacceptably high and have not been significantly improved by alternative antifungal strategies to date. Over the last few years, rapid methods for the clinical-scale generation of functionally active and well characterized antifungal T(H)1 cells have become available. In addition, current data on the use of donor-derived virus-specific T cells in allogeneic stem cell transplantation suggest that the risk of severe adverse events, in particular the risk of graft-versus-host disease, is negligible. Therefore, adoptive antifungal immunotherapeutic strategies should be evaluated in clinical trials. However, one has to recognize that these trials are only meaningful with sufficiently large and homogenous cohorts of patients and if the settings of adoptive antifungal immunotherapy are comparable. Ultimately, the strategy of adoptively transferring antifungal immune responses might improve the outcome in hematopoietic stem cell recipients suffering from invasive fungal infection. PMID- 20586683 TI - Problems diagnosing bipolar disorder in clinical practice. PMID- 20586684 TI - Futility of the autoimmune orthodoxy in multiple sclerosis research. PMID- 20586686 TI - Ziprasidone HCl capsules for the adjunctive maintenance treatment of bipolar disorder in adults. AB - This article reviews the evidence for the use of ziprasidone for the maintenance treatment of bipolar I disorder in adults as an adjunct to lithium or valproate, as approved by the US FDA in 2009. Ziprasidone is an 'atypical' or 'second generation' antipsychotic that has garnered clinical interest because of its metabolically friendly tolerability profile. A placebo-controlled trial was conducted in subjects whose most recent episode was manic or mixed, with or without psychotic features, and with symptoms that began no more than 90 days prior to the screening visit. Patients were stabilized during a 10-16-week, open label period on the combination of ziprasidone 80-160 mg/day plus lithium (0.6 1.2 mEq/l) or valproate (50-125 microg/ml). Patients whose symptoms stabilized for 8 consecutive weeks were randomized to either continue combination treatment with adjunctive ziprasidone or receive lithium or valproate with adjunctive placebo for up to 24 weeks of double-blind treatment. The primary outcome measure was time to intervention for a mood episode during the double-blind period, tested statistically using survival analysis and assessing Kaplan-Meier curves. Of the 584 patients enrolled in the open-label period, 241 (41%) completed. A total of 238 subjects were analyzed for efficacy in the double-blind period (ziprasidone 127, placebo 111). Ziprasidone was superior to placebo in increasing the time to recurrence of a mood episode (p = 0.0104) during the 6 months of double-blind treatment. Only 19.7% (25 out of 127) of the ziprasidone subjects required intervention for a mood episode, compared with 32.4% (36 out of 111) of the placebo subjects (number needed to treat [NNT] 8; 95% CI: 5-62). The most robust effects were noted for the combination of ziprasidone and lithium and for the avoidance of manic/mixed episodes. Ziprasidone had no remarkable effect on weight or blood glucose. Limitations of this study include the enriched sample and exclusion of the most severely ill, and the inclusion of only those patients whose most recent bipolar episode was manic or mixed. Indirect comparisons of adjunctive ziprasidone with adjunctive quetiapine reveals a lower (i.e., more robust) NNT for quetiapine in terms of proportions of subjects experiencing a mood event (NNT: 4), but a higher incidence of bodyweight gain of at least 7% from baseline. PMID- 20586687 TI - New perspectives on molecular and cellular mechanisms of neuroprotection and neuroregeneration: part I. AB - Recent developments in the rapidly advancing area of neuroprotection and neuroregeneration necessitated the need to gather over 50 of the world's leading experts under the umbrella of the Global College of Neuroprotection and Neuroregeneration (GCNN) in its 7th Annual Meeting in Stockholm, Sweden. In this meeting, top policy-makers, together with world leaders in pharmaceutical industries, discussed the urgent need to develop new pharmaceuticals, as well as using a combination of existing ones, to treat CNS disorders in order to improve the current status of healthcare. In addition, nanobiotechnologists proposed the use of a new formulation of drugs using nanotechnologies for enhanced drug delivery to the brain for better therapeutic efficacy of the neuroprotective agents. The deliberations in this meeting provide new perspectives on the molecular and cellular mechanisms of neuroprotection and neuroregeneration that could be utilized to improve the existing healthcare for the benefit of mankind. PMID- 20586688 TI - Diagnosis and treatment of postpartum bipolar depression. AB - The postpartum period is a time of increased risk of new-onset psychiatric illness, hospital admissions and out-patient psychiatric care for new mothers. Research into postpartum mood disorders has focused primarily on major depressive disorder, and has overlooked the study of bipolar disorder, particularly bipolar II disorder and bipolar disorder not otherwise specified. Failure to properly diagnose postpartum bipolar disorder may delay the initiation of appropriate treatment, lead to inappropriate treatment - thereby precipitating (hypo)mania, rapid cycling or a mixed episode - or result in polypharmacy and treatment refractoriness. The most serious consequence, however, is the high risk of infanticide and suicide among women with postpartum bipolar disorder. While no specific screening tools have been validated for postpartum mania or bipolar depression, symptoms of hypomania, atypical depression, a family history of bipolar disorder and a rapid onset of depressive symptoms following delivery may suggest a bipolar diathesis. In the absence of any pharmacological or psychotherapeutic treatments to guide clinical decision-making, it is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of non-postpartum bipolar depression, using medications that are compatible with lactation. PMID- 20586689 TI - Psychopharmacology of pediatric bipolar disorder. AB - This comprehensive literature review incorporates research studies evaluating the effectiveness of psychotropic medications in children and adolescents with pediatric bipolar disorder. Research articles were obtained using Medline. Open label studies, prospective and retrospective chart reviews and randomized controlled trials evaluating the effectiveness of medication in pediatric bipolar disorder with greater than ten subjects are included in this article. Antipsychotics, anticonvulsants and lithium as monotherapy, as well as their use in combination treatment, were evaluated to determine their effectiveness in pediatric bipolar disorder. Clinical recommendations of medication and management strategies are made from a synthesis of the data. In addition, adherence concerns caused by adverse effects and nonresponse as they impact physical and mental health are addressed. PMID- 20586690 TI - Cognitive-behavioral therapy for bipolar disorder. AB - Bipolar disorder is one of the most serious and prevalent psychiatric disorders. The aim of the present article is to review the efficiency of cognitive behavioral therapy (CBT) for bipolar patients. Some studies show consistent evidence that cognitive therapy, concomitant to psycho-education and pharmacological treatment, offers efficacy in different phases of the disease. In most of the studies, patients undergoing CBT showed improvements in quality of life, with a reduction in both frequency and duration of mood episodes, as well as higher degrees of compliance and fewer hospitalizations. More studies are required to prove the effectiveness of CBT for bipolar disorder in the context of standardizing diagnostic criteria and measuring instruments to evaluate the disorder's different phases and severity. PMID- 20586691 TI - Sleep deprivation in depression. AB - Sleep deprivation (SD) is a powerful antidepressant treatment that shows antidepressant responses within hours in 40-60% of depressed patients. In more than 80% of responders to SD, a relapse into depression occurred after the recovery night. In addition, it serves as an excellent tool to examine the neurobiological disturbance of depression and may profoundly contribute to the development of new specific and more rapidly acting antidepressants. The reason why SD works and relapses occur is still unclear. A key to solve this problem is to include the current knowledge about the neurobiological disturbance of depression in research, with a focus on neurobiological aspects of sleep and SD (sleep EEG, neuroendocrinology, neurochemistry and chronobiology). Based on findings from these different areas, different strategies to stabilize the antidepressant effect of SD have been applied. This article provides an overview of clinical and neurobiological responses related to SD in depression. PMID- 20586692 TI - What is the effectiveness of the use of polyunsaturated fatty acid omega-3 in the treatment of depression? AB - This systematic review aims to identify the effect of polyunsaturated fatty acid omega-3 on depressive disorder. A bibliographical search was conducted in the databases SciELO, PubMed and ISIWEB. The keywords used were: "depression" and "omega-3 fatty acids", "depression" and "omega-3 polyunsaturated fatty acid", "depression" and "n-3 fatty acids". A total of 19 studies were identified: four double-blind randomized studies, four cohorts, two cross-sectional lines and nine case-controls. Only five studies presented dropout of less than 30% and controlled for the most important confounding variables. Of the evaluated studies, 13 showed a significant positive association between omega-3 and depression, while six studies did not show a relationship between the referred variables. Therefore, future studies with similar methodology would aid in determining the precise effect of omega-3 on depressive disorders. PMID- 20586693 TI - Neurodegeneration in schizophrenia. AB - The neurodegenerative aspect of schizophrenia presupposes gene-environmental interactions involving chromosomal abnormalities and obstetric/perinatal complications that culminate in predispositions that impart a particular vulnerability for drastic and unpredictable precipitating factors, such as stress or chemical agents. The notion of a neurodevelopmental progression to the disease state implies that early developmental insults, with neurodegenerative proclivities, evolve into structural brain abnormalities involving specific regional circuits and neurohumoral agents. This neurophysiological orchestration is expressed in the dysfunctionality observed in premorbid signs and symptoms arising in the eventual diagnosis, as well as the neurobehavioral deficits reported from animal models of the disorder. The relative contributions of perinatal insults, neonatal ventral hippocampus lesion, prenatal methylazoxymethanol acetate and early traumatic experience, as well as epigenetic contributions, are discussed from a neurodegenerative view of the essential neuropathology. It is implied that these considerations of factors that exert disruptive influences upon brain development, or normal aging, operationalize the central hub of developmental neuropathology around which the disease process may gain momentum. Nonetheless, the status of neurodegeneration in schizophrenia is somewhat tenuous and it is possible that brain imaging studies on animal models of the disorder, which may describe progressive alterations to cortical, limbic and ventricular structures similar to those of schizophrenic patients, are necessary to resolve the issue. PMID- 20586694 TI - Clinical and psychosocial significance of trauma history in schizophrenia spectrum disorders. AB - Interest has arisen in the role stressors play in the development and outcome of schizophrenia. This article examines one such stressor - trauma experienced prior to the onset of illness. We discuss research on the incidence, types and correlates of trauma in schizophrenia, and review work suggesting trauma may increase risk for schizophrenia. Studies are further detailed that have examined links between trauma and heightened levels of positive symptoms and anxiety, and poorer social, vocational and treatment outcomes. Here, literature on approaches to addressing trauma among persons with schizophrenia is presented, along with a commentary that points to the need for research on how trauma might increase the risk for the development of schizophrenia and worsen the symptoms and treatment outcome of individuals in recovery from this illness. PMID- 20586695 TI - Suicide in schizophrenia. AB - Schizophrenia is a disorder with an estimated suicide risk of 4-5%. Many factors are involved in the suicidal process, some of which are different from those in the general population. Clinical risk factors include attempted suicide, depression, male gender, substance abuse and hopelessness. Biosocial factors, such as a high intelligence quotient and high level of premorbid function, have also been associated with an increased risk of suicide in patients with schizophrenia. Suicide risk is especially high during the first year after diagnosis. Many of the suicides occur during hospital admission or soon after discharge. Management of suicide risk includes both medical treatment and psychosocial interventions. Still, risk factors are crude; efforts to predict individual suicides have not proved useful and more research is needed. PMID- 20586696 TI - Prevention of schizophrenia. AB - This article reviews progress made in the identification of vulnerability to schizophrenia in genetic high-risk groups. Dimensions of vulnerability include cognitive, clinical and social functions, among others. Based on studies of dysfunction in these areas, specialized programs are being developed to focus on recognizing rates and patterns of transition to schizophrenia, and intervention techniques that include psychopharmacological and psychotherapeutic techniques. After considering a current conceptualization of schizotaxia, the identification of novel endophenotypes that may include brain function, molecular biology or other medical functions will be considered, in addition to clinical, social and neuropsychological measures. Eventually, it is hoped that areas of vulnerability will coalesce into validated syndromes of liability that can be used to identify individuals who are most likely to develop schizophrenia-related disorders. This strategy will then allow the formation of more homogenous treatment groups to use in developing early intervention and prevention strategies in the not-too-distant future. PMID- 20586698 TI - Antioxidant approaches for the treatment of Alzheimer's disease. AB - Oxidative stress is an important factor, and one that acts in the earliest stages, of Alzheimer's disease (AD) pathogenesis. The reduction of oxidative stress has been tested as a therapy for AD. While the trial of vitamin E supplementation in moderately severe AD is the most promising so far, it also reveals the limitations of general antioxidant therapies that simply lower oxidative stress and, therefore, the complexity of the redox system. The multiple contributing factors that foster the clinical manifestations of AD should be considered when designing antioxidative stress therapy. In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches. PMID- 20586699 TI - Autophagy in Alzheimer's disease. AB - Autophagy is a degradation pathway for the turnover of dysfunctional organelles or aggregated proteins in cells. Extensive literature exists supporting a causative role of mitochondrial dysfunction and amyloid-beta protein in the pathogenesis of Alzheimer's disease (AD). Furthermore, a link between mitochondrial dysfunction, amyloid-beta levels and autophagy has been reported to occur in AD. However, it is not yet clear if autophagy plays a causative role, a protective role or is a consequence of the disease process itself. Understanding the exact role of autophagy in different stages of AD progression may help to design more effective therapeutic strategies. A central issue in developing therapies for neurodegenerative diseases involves understanding why and when responses to stress or injury can help prevent neuronal degeneration and death. PMID- 20586700 TI - Ceramic encapsulation with polymer via co-axial electrohydrodynamic jetting. AB - Co-flowing media of a polymeric solution (30 wt% polymethylsilsesquioxane in ethanol) and a ceramic suspension (10 wt% alumina in glycerol) were subjected to an electric field. The flow rates of the media (10-30 microL min(-1)) and the applied voltage (0-11 kV) were varied systematically during the experimentation by making gradual increments to each variable, which enabled the construction of a mode selection map. Under co-flowing conditions, with the flow rate of polymer solution (outer needle) twice that of the ceramic suspension (inner needle), encapsulated droplets of polymer-coated alumina were produced within stable cone jet mode. These were collected in a thin film of water and the resultant particle size varied between 1 and 38 microm. Encapsulation was confirmed with scanning electron microscopy and element analysis. PMID- 20586697 TI - Management of antipsychotic-related weight gain. AB - Despite variations across individuals and agents, antipsychotics are associated with clearly documented weight gain and adverse metabolic effects. Although increased appetite/caloric intake and various receptors, hormones and peptides have been implicated, biological mechanisms contributing to the increase in weight and glucose and lipid abnormalities with antipsychotics are largely unknown. This has hampered the creation of antipsychotics that are free of cardiometabolic effects, even in antipsychotic-naive/early-phase patients, as well as the development of strategies that can prevent or drastically diminish the adverse cardiometabolic effects. In general, three strategies can reduce the cardiometabolic risk of antipsychotics: switching to a less orexigenic/metabolically adverse antipsychotic; adjunctive behavioral treatments; and adjunctive pharmacologic interventions. However, each of these strategies has only been shown to be modestly effective. Among different behavioral interventions (N = 14, n = 746), group and individual treatment, dietary counseling and cognitive-behavioral therapy seem to be similarly effective. Among 15 different pharmacologic strategies (N = 35, n = 1629), only metformin, fenfluramine, sibutramine, topiramate and reboxetine were more effective than placebo, with the most evidence being available for metformin, and no head-to head trials comparing individual pharmacologic interventions. However, even in the most successful trials the risk reduction was modest. Weight was not decreased to a pretreatment level, and despite superiority compared with placebo, weight gain still often occurred, particularly in antipsychotic-naive patients and when interventions were 'preventively' coinitiated with antipsychotics. Future research should focus on combining treatment modalities or agents and on exploring novel mechanism-based interventions. PMID- 20586701 TI - Transient receptor potential vanilloid-1 antagonists: a survey of recent patent literature. AB - IMPORTANCE OF THE FIELD: Transient receptor potential vanilloid-1 (TRPV1, vanilloid receptor-1) is a nonspecific cation channel that can be activated by multiple endogenous stimuli and by capsaicin, the active ingredient in chili peppers. TRPV1 is expressed predominantly on sensory neurons where it is proposed to serve as a key nodal point in pain transmission pathways. Pharmacological blockade of TRPV1 represents a compelling strategy for the treatment of a variety of disease states, particularly those requiring chronic pain management. AREA COVERED IN THE REVIEW: This review summarizes patent literature and progress in defining the utility of small molecule TRPV1 antagonists during 2008-2009. WHAT THE READER WILL GAIN: Representative compounds and key characterization data comprising multiple chemical series are highlighted. TAKE HOME MESSAGE: The continued profusion of reports, in both the primary and patent literature, attests to the sustained interest in the TRPV1 class of therapeutics. Although a number of compounds have now been brought forward for human clinical trials, the therapeutic utility of TRPV1 antagonists is yet to be validated unequivocally. PMID- 20586702 TI - The prefrontal cortex modulates category selectivity in human extrastriate cortex. AB - Different categories of visual objects evoke distinct stimulus-evoked sensory responses in extrastriate visual cortex. Although numerous lines of evidence support a distinct representational neural architecture, the mechanisms underlying the modulation of the category selectivity by top-down influences remains uncertain. In this study, we investigate the causal role of the PFC in the modulation of evoked activity to face and scene stimuli in the extrastriate cortex. We used two experimental approaches to disrupt prefrontal cortical function-repetitive TMS to PFC in healthy participants (Experiment 1) and focal PFC lesions in stroke patients (Experiment 2). After these perturbations to normal PFC function (pre- vs. post-TMS and lesion vs. intact hemisphere), stimulus-evoked activity in extrastriate cortex exhibited less distinct category selectivity to faces and scenes. These two experiments provide convergent evidence highlighting a direct role of PFC in the top-down modulation of bottom up visual signals. PMID- 20586703 TI - A modified cementing technique using BoneSource to augment fixation of the acetabulum in a sheep model. AB - BACKGROUND AND PURPOSE: Our aim was to assess in an animal model whether the use of HA paste at the cement-bone interface in the acetabulum improves fixation. We examined, in sheep, the effect of interposing a layer of hydroxyapatite cement around the periphery of a polyethylene socket prior to fixing it using polymethylmethacrylate (PMMA). METHODS: We performed a randomized study involving 22 sheep that had BoneSource hydroxyapatite material applied to the surface of the acetabulum before cementing a polyethylene cup at arthroplasty. We studied the gross radiographic appearance of the implant-bone interface and the histological appearance at the interface. RESULTS: There were more radiolucencies evident in the control group. Histologically, only sheep randomized into the BoneSource group exhibited a fully osseointegrated interface. Use of the hydroxyapatite material did not give any detrimental effects. In some cases, the material appeared to have been fully resorbed. When the material was evident in histological sections, it was incorporated into an osseointegrated interface. There was no giant cell reaction present. There was no evidence of migration of BoneSource to the articulation. INTERPRETATION: The application of HA material prior to cementation of a socket produced an improved interface. The technique may be useful in humans, to extend the longevity of the cemented implant by protecting the socket interface from the effect of hydrodynamic fluid flow and particulate debris. PMID- 20586704 TI - Native albumin for targeted drug delivery. AB - IMPORTANCE IN THE FIELD: Activated cells metabolize albumin to cover their increased need for amino acids and energy. In inflamed, diseased and malignant tissue, extravasation of macromolecules into the tissue is upregulated. Drug carriers such as albumin have been used to target specifically diseased and malignant cells, resulting in higher efficacy of treatment and reduced side effects. AREAS COVERED IN THIS REVIEW: Owing to its advantageous biochemical and pharmacological properties, albumin has been regarded as an interesting candidate as a drug carrier. Covalent coupling to albumin carries drugs specifically to tumors and sites of inflammation, leading to reduced side effects as long as the native structure of albumin is unchanged. In this review, the means of coupling drugs to native albumin as well as exemplary studies for the use of albumin as drug carrier are summarized and discussed. WHAT THE READER WILL GAIN: An overview of the state-of-the-art using albumin as drug carrier for specific accumulation in tumors and inflammatory cells using the advantageous properties of native albumin is given in this review. TAKE HOME MESSAGE: Native albumin is an effective drug carrier to sites of inflammation or malignancy. PMID- 20586705 TI - Gastric emptying of non-disintegrating solid drug delivery systems in fasted state: relevance to drug dissolution. AB - IMPORTANCE OF THE FIELD: Knowledge of gastric emptying (GE) of solid drug delivery systems (DDS) is meaningful for the development of new DDS as it enables the design of in vitro dissolution experiments with conditions close to those in vivo in order to predict drug plasma concentration profiles with high reliability. AREAS COVERED IN THIS REVIEW: Gastric emptying of non-disintegrating pellets, tablets and mini-tablets in the fasted state is described on the basis of various studies performed in the last 30 years, which have evaluated the emptying process mostly by gamma scintigraphy. Different influences on GE and mathematical models describing GE kinetics of single and multiunit dosage forms are represented. A discussion on the implementation of these data in the development of drug dissolution testing procedures is given. WHAT THE READER WILL GAIN: Readers will gain an insight into the kinetics and mechanisms of GE processes. Some suggestions on the use of the obtained knowledge in biopharmaceutical testing of DDS are also given. TAKE HOME MESSAGE: Gastric emptying of non-disintegrating solid DDS is a very important process, which might influence drug dissolution, bioavailability and the plasma concentration profile. It is reasonable to consider this process in biopharmaceutical testing of these DDS. PMID- 20586706 TI - Design-related risk factors for revision of primary cemented stems. AB - BACKGROUND AND PURPOSE: Even small design variables of the femoral stem may influence the outcome of a hip arthroplasty. We investigated whether design related factors play any role in the risk of non-aseptic revision of the 3 most frequently used primary cemented stem designs in the Swedish Hip Arthroplasty Register. PATIENTS AND METHODS: We studied 71,184 primary cemented femoral stem implants (21,008 Exeter polished stems, 43,036 Lubinus SPII stems, and 7,140 Spectron EF Primary stems) that were inserted from 1999 through 2006. Design specific characteristics were analyzed using separate Cox regression models that were adjusted for sex, age, diagnosis, incision, and number of operations (first vs. second). RESULTS: The crude revision rate varied between 0.8% (Lubinus SPII) and 1.4% (Spectron Primary). For the Exeter stem, the smallest femoral head diameter (22 mm) was associated with a higher risk of revision. No other design specific parameters influenced the risk of revision of the Exeter stem. The smallest Lubinus stem size, a stem with extended neck length combined with a femoral head with increasing neck length, or the use of a cobalt-chromium head had a negative influence on the outcome. For the Spectron stem, the risk of revision was elevated for the smallest stem and for increasing offset calculated as the combined effect of high offset design and increasing neck length. INTERPRETATION: Overall revision rates were low, but for two of the stems studied design factors such as size and neck length or offset influenced the risk of non aseptic revision. PMID- 20586707 TI - Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. AB - IMPORTANCE OF THE FIELD: Antipsychotic medications are the cornerstone of treatment in schizophrenia, and a large body of data confirms the value of ongoing and continuous antipsychotic pharmacotherapy in controlling symptoms and preventing relapse. However, nonadherence with antipsychotic treatment is a significant issue, with estimates as high as 90%. AREAS COVERED IN THIS REVIEW: This review focuses on long-acting injectable (LAI) antipsychotics and their role in the treatment of schizophrenia. The existing literature, with an emphasis on clinical evidence, is assessed. This includes both reviews and specific trials that examine LAIs and compare them with oral agents, with measures ranging from relapse and rehospitalization to adherence. Both advantages and limitations (e.g., challenges in terms of dose titration and time to steady state) are examined. WHAT THE READER WILL GAIN: This overview serves as an update for clinicians wishing to understand LAIs better, including the newer second generation antipsychotics (SGAs) with this formulation available, and their potential role in the long-term treatment of individuals with schizophrenia. TAKE HOME MESSAGE: Despite identified advantages, LAIs are not used as widely as might be expected. It would seem that clinicians are at least partly responsible for this, influenced by our own misperceptions (e.g., that LAIs are not acceptable to patients) and, perhaps, misinformation (e.g., increased side effect risk). As clinicians, we may well be shortchanging LAIs if we position them as a treatment of last resort for the multi-episode, nonadherent, 'revolving door' patient, especially given recent evidence underscoring their potential benefits in first episode patients. The search for new and more effective antipsychotics will continue, but we are reminded that suboptimal outcomes may have as much to do with nonadherence as inadequate treatments. Evidence has established that LAI antipsychotics demonstrate distinct benefits in this regard, and we would be remiss if we did not exploit this already available strategy. As well as additional research, we need to rethink how we position these agents in our treatment algorithms if we are to maximize their potential. PMID- 20586708 TI - Treatment of gastric marginal zone lymphoma of MALT type. AB - IMPORTANCE OF THE FIELD: Gastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT type) represent approximately half of all cases of lymphomas arising in the stomach. They have been strongly associated with chronic Helicobacter pylori (H. pylori) gastritis. Treatment aimed at eradicating this infection results in lymphoma remissions in the majority of patients (approximately 80%) and this represents a unique case of anticancer treatment based on the eradication of the causing factor. AREAS COVERED IN THIS REVIEW: The effects of H. pylori eradication in suppressing the growth of this lymphoma with particular emphasis on the long-term disease control results are presented in this review. Trials of different treatment modalities for patients not responding to antibiotics are also covered. WHAT THE READER WILL GAIN: Understanding of the effects of H. pylori eradication on suppressing the growth of gastric MALT lymphoma. Readers will learn how to distinguish between clinical, histological and molecular remission of the lymphoma and will learn alternative treatments for patients with H. pylori-negative disease and for cases not responding to eradication. TAKE HOME MESSAGE: Gastric MALT lymphoma has an indolent course and most patients can achieve durable disease control after only anti-H. pylori therapy. For patients not responding to antibiotics, randomized trials are needed to define the best treatment modality. PMID- 20586709 TI - An expert opinion on postoperative pain management, with special reference to new developments. AB - IMPORTANCE OF THE FIELD: Recently, much attention has been directed towards the effect of opioid-sparing strategies on postoperative morbidity and hospitalization, and on different nociceptive mechanisms involved in various postoperative pain states and surgical procedures. This has resulted in an increased interest in secondary, or adjunct, analgesics and procedure-specific analgesic methods. AREAS COVERED IN THIS REVIEW: The present paper aims to review and discuss recent developments within the field of various adjunct, systemic analgesics and local/regional anesthetic methods for management of postoperative pain, based on evidence from randomized, clinical trials published within the last 5 years. WHAT THE READER WILL GAIN: The reader will gain insight into the current role of pregabalin, glucocorticoids and systemic lidocaine for the management of postoperative pain. In addition, the current status of local infiltration analgesia for hip and knee arthroplasty, transversus abdominis plane block for abdominal operations, and the analgesic effect of wound instillation of capsaicin are reviewed. TAKE HOME MESSAGE: The evidence of a substantial analgesic effect of pregabalin on acute postoperative pain is questionable, and more convincing evidence of the role of glucocorticoids and systemic lidocaine is needed before they should be recommended as analgesics in daily clinical practice. Local infiltration analgesia after hip and knee arthroplasty, transversus abdominis plane block after abdominal operations and local application of capsaicin lend some promise, but there is still a lack of well performed RCTs to draw any firm conclusions. Procedure-specific analgesic combinations within well-defined rehabilitation paradigms should be explored further to reduce adverse effects associated with the use of conventional analgesic treatment protocols, and to improve postoperative outcome. PMID- 20586710 TI - Sorafenib: a clinical and pharmacologic review. AB - IMPORTANCE OF THE FIELD: Sorafenib is an oral receptor tyrosine kinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases (vascular endothelial growth factor receptors 1, 2, 3 and platelet-derived growth factor-beta, Flt-3 and c-kit) that are implicated in tumorigenesis and tumor progression. Sorafenib is approved for the treatment of advanced inoperable hepatocellular cancer and advanced renal cell cancer. AREAS COVERED IN THIS REVIEW: The findings from the major Phase III studies that led to FDA approval of this drug for the above indications are reviewed. Key aspects of sorafenib pharmacology, dosing in the presence of organ dysfunction, toxicities and weaknesses of the research done so far are summarized. WHAT WILL THE READER GAIN: The reader will have the knowledge of the major studies that form the basis of the clinical use of sorafenib, information on the upcoming Phase III trials that could lead to changes in clinical practice and some insights on aspects of the drugs' mechanism of action and toxicity that still remain unclear. TAKE HOME MESSAGE: Sorafenib is a well-tolerated oral antiangiogenic agent approved for treatment of two angiogenesis-driven cancers. Studies to broaden the clinical indications and increase understanding of the clinical and laboratory biomarkers of response are needed. PMID- 20586711 TI - Targeting epidermal growth factor receptor in the treatment of non-small-cell lung cancer. AB - IMPORTANCE OF THE FIELD: The management of non-small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade, with the survival advantage demonstrated by the incorporation of anti-epidermal growth factor receptor (EGFR) agents to the standard treatment of advanced/metastatic NSCLC. AREAS COVERED IN THIS REVIEW: We review the existing data regarding the distinct anti-EGFR agents in the NSCLC treatment and the potential role of the investigated biomarkers in the clinical outcome. WHAT THE READER WILL GAIN: Tyrosine kinase inhibitors have been used in first-line, second-line and more settings with extremely good results in a subgroup of patients. Cetuximab remains the only anti-EGFR monoclonal antibody to show survival benefit when combined with a cytotoxic agent in the front-line setting. Anti-EGFR treatment is associated with a dramatic clinical benefit in a subgroup of patients, emphasizing the importance of customizing treatment. Several biomarkers have been investigated for their predictive or prognostic value. Validation of identification of biomarkers remains a focus of intense research that may ultimately guide therapeutic decision making, as none of these is considered ideal to discriminate responding from non-responding patients. However, the current evidence of the EGFR mutation analysis from a recent randomised trial suggests that EGFR mutation analysis is quite a good predictive marker for responsiveness to anti-EGFR TKIs. Moreover, the identification of surrogate markers to indicate optimal activity of the anti EGFR agent is also needed. This review article provides data from large clinical trials using anti-EGFR agents and correlates these results with the tested biomarkers. TAKE HOME MESSAGE: EGFR inhibition has shown very encouraging results and has improved the outcome of the NSCLC treatment. However, a plateau of significant clinical benefit seems to have been reached and we believe that the time to move away from the traditional treatment approach to more individualizing therapies has come. PMID- 20586712 TI - Systemic therapy for metastatic renal cell carcinoma in treatment naive patients: a risk-based approach. AB - IMPORTANCE OF THE FIELD: Kidney cancer is the ninth most common cancer in the USA, with an annual incidence of approximately 55,000 cases per year. Over 13,000 patients are estimated to die from this disease annually. Cloning of the VHL gene, recognition of the associated abnormalities in sporadic clear-cell carcinoma, and its role as a regulator of the hypoxic response, were important milestones in our understanding of renal-cell carcinoma (RCC) biology and the recognition of the vascular endothelial growth factor (VEGF) dependency of RCC. A variety of clinical features, including histologic features, prognostic factors, and patient history of comorbid illness, provide the framework in which the results of recent clinical trials and regulatory approvals of these agents are utilized to develop treatment recommendations for the largest metastatic patient RCC group, the therapy naive individual. AREAS COVERED IN THIS REVIEW: The rationale for use of VEGF-targeted therapy in advanced RCC patients and the recently developed treatment options for these individuals are reviewed. Regulatory approval of sorafenib for the treatment of metastatic RCC (mRCC), was followed by the approval of sunitinib, temsirolimus, bevacizumab plus interferon (IFNalpha), everolimus, and--most recently--pazopanib. These licences were granted from late 2005 through late 2009, a very short span of 4 years. In treatment-naive mRCC patients, sunitinib, sorafenib, pazopanib, bevacizumab + IFNalpha, and temsirolimus were approved by the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMEA). The clinical trials and data supporting these approvals are reviewed. WHAT WILL THE READER GAIN: This review examines these developments and provides the reader an overview and understanding of available current systemic therapy options for treatment-naive mRCC patients. TAKE HOME MESSAGE: As multiple treatment options are now available for treatment naive mRCC patients, an understanding of how to utilize this group of agents is required. The use of various clinical features allows a rational approach to therapy selection. These features include prior treatment status, histologic subtype, and prognostic group. Further refinement of therapy selection is required and will require further biologic information as well as comparative randomized trials. PMID- 20586713 TI - Iloperidone for schizophrenia. AB - IMPORTANCE OF THE FIELD: No existing antipsychotic adequately controls all symptoms associated with schizophrenia. Also, no antipsychotic adequately benefits most patients with this disorder. Finally, the safety and tolerability of each antipsychotic frequently dictate the choice of agent. AREAS COVERED IN THE REVIEW: The mechanism of action of iloperidone, its efficacy and its safety and tolerability when used to treat patients with schizophrenia. WHAT THE READER WILL GAIN: An appreciation of the potential advantages and disadvantages of iloperidone when used for the treatment of schizophrenia. TAKE HOME MESSAGE: Iloperidone is a recent addition to the current group of second-generation antipsychotics. While it may share many qualities with other agents in this class, its unique neuroreceptor signature and adverse-effect profile may prove beneficial in clinical practice. PMID- 20586716 TI - Studies of benzothiadiazine derivatives as hepatitis C virus NS5B polymerase inhibitors using 3D-QSAR, molecular docking and molecular dynamics. AB - In order to explore the structure-activity correlation of benzothiadiazine series as inhibitors of genotype 1a HCV polymerase, a set of ligand- and receptor-based 3D-QSAR models were, for the first time, developed in the present work employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) for 239 promising molecules. In addition, homology modeling, docking analysis, and molecular dynamics simulation (MD) were also applied to elucidate the probable binding modes of these inhibitors at the allosteric site of the enzyme. The statistical model validations assure the reliability of the obtained QSAR models. Changes in the binding affinity of the inhibitors attributing to modifications in the aromatic rings could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. (i) Hydrophobic substituents with similar size of benzo group like isosteres are preferential at positions 1 and 2 (ring B of benzothiadiazines). (ii) Substituents at position-3 containing a linear alkyl chain (four or five carbon atoms) or a branched alkyl chain (five-eight carbons) can increase the inhibitory activity by one to two orders of magnitude. (iii) A polar substituent like methanesulfonamide group at position-14 can enhance the activity of the drug by providing a hydrogen bonding interaction with the protein target. The results obtained from this work provide important guidelines in design of novel benzothiadiazine analogs as inhibitors of HCV genotype 1a NS5B. PMID- 20586715 TI - Non-ATP competitive protein kinase inhibitors. AB - Protein kinases represent an attractive target in oncology drug discovery. Most of kinase inhibitors are ATP-competitive and are called type I inhibitors. The ATP-binding pocket is highly conserved among members of the kinase family and it is difficult to find selective agents. Moreover, the ATP-competitive inhibitors must compete with high intracellular ATP levels leading to a discrepancy between IC50s measured by biochemical versus cellular assays. The non-ATP competitive inhibitors, called type II and type III inhibitors, offer the possibility to overcome these problems. These inhibitors act by inducing a conformational shift in the target enzyme such that the kinase is no longer able to function. In the DFG-out form, the phenylalanine side chain moves to a new position. This movement creates a hydrophobic pocket available for occupation by the inhibitor. Some common features are present in these inhibitors. They contain a heterocyclic system that forms one or two hydrogen bonds with the kinase hinge residue. They also contain a hydrophobic moiety that occupies the pocket formed by the shift of phenylalanine from the DFG motif. Moreover, all the inhibitors bear a hydrogen bond donor-acceptor pair, usually urea or amide, that links the hinge-binding portion to the hydrophobic moiety and interacts with the allosteric site. Examples of non ATP-competitive inhibitors are available for various kinases. In this review small molecules capable of inducing the DFG-out conformation are reported, especially focusing on structural feature, SAR and biological properties. PMID- 20586717 TI - Synthesis and preliminary screening of novel tryptamines as 5-HT4 receptor ligands. AB - For the development of novel 5-HT(4) receptor ligands we have designed and synthesized two series of 5-methoxytryptamine derivatives varying the substitution on the primary amine. Their biological activities were evaluated in a receptor binding assay where a subset of compounds showed comparable potency to the agonists serotonin and 5-methoxytryptamine. Structure-activity analyses have highlighted promising avenues for further synthetic work and binding modes were proposed by docking these compounds into a homology model of the 5-HT(4) receptor. PMID- 20586714 TI - Medicinal chemistry of ATP synthase: a potential drug target of dietary polyphenols and amphibian antimicrobial peptides. AB - In this review we discuss the inhibitory effects of dietary polyphenols and amphibian antimicrobial/antitumor peptides on ATP synthase. In the beginning general structural features highlighting catalytic and motor functions of ATP synthase will be described. Some details on the presence of ATP synthase on the surface of several animal cell types, where it is associated with multiple cellular processes making it an interesting drug target with respect to dietary polyphenols and amphibian antimicrobial peptides will also be reviewed. ATP synthase is known to have distinct polyphenol and peptide binding sites at the interface of alpha/beta subunits. Molecular interaction of polyphenols and peptides with ATP synthase at their respective binding sites will be discussed. Binding and inhibition of other proteins or enzymes will also be covered so as to understand the therapeutic roles of both types of molecules. Lastly, the effects of polyphenols and peptides on the inhibition of Escherichia coli cell growth through their action on ATP synthase will also be presented. PMID- 20586718 TI - New therapeutic strategy for Parkinson's and Alzheimer's disease. AB - The development of potential neuroprotective therapies for neurodegenerative diseases (Parkinson's and Alzheimer's Disease) must be based on understanding their molecular and biochemical pathogenesis. Many potential pathways of neuronal cell death have been implicated in a mouse model of neurodegenerative disease, including excitotoxicity, toxicity from reactive oxygen species (superoxide anion, nitric oxide, hydroxyl radical), apoptosis (caspase-dependent and independent pathways), necrosis and glial injury. Some agents that act on these pathways may be available for protecting the brain against chronic neurodegenerative conditions like Parkinson's and Alzheimer's disease. Drugs currently used to treat neurological disease and injuries provide temporary relief of symptoms but do not stop or slow the underlying neurodegenerative process. Restorative therapies for Parkinson's Disease are currently focused on cell replacement and administration of growth factors and small-molecule neurotrophic agents. The new experimental drugs, by contrast, target the common, underlying cause of destructive process of brain cell death. For example, p53 inhibitors attack a key protein involved in nerve cell death and represent a new strategy for preserving brain function following sudden injury or chronic disease. Analogues of pifithrin-alpha (PFT), which was shown in previous studies to inhibit p53, were designed, synthesized and tested to see whether they would work against cultured brain cells and animal models of neurodegenerative disease. Moreover, several agents based on the predominant anti-amyloid strategy, targeting amyloid-beta (Aβ) peptide, which aggregates in the plaques that are a hallmark of Alzheimer's disease, would affect disease progression. Researchers are already making great strides in developing a vaccine for this progressive brain disorder. Immunization could offer a way to blunt or even prevent the deadly, memory-robbing disease. Here we review many of potential neuroprotective therapies, and strategies that might be suited to the development of innovative approaches that prevent degeneration and restore function in Parkinson's disease. PMID- 20586719 TI - Involvement of cytosolic phospholipase A(2), calcium independent phospholipase A(2) and plasmalogen selective phospholipase A(2) in neurodegenerative and neuropsychiatric conditions. AB - Enzymes belonging to the PLA(2) superfamily catalyze the hydrolysis of unsaturated fatty acids from the sn-2 position of glycerol moiety of neural membrane phospholipids. The PLA(2) superfamily is classified into cytosolic PLA(2) (cPLA(2)), calcium-independent PLA(2) (iPLA(2)), plasmalogen-selective PLA(2) (PlsEtn-PLA(2)) and secretory PLA(2) (sPLA(2)). PLA(2) paralogs/splice variants/isozymes are part of a complex signal transduction network that maintains cross-talk among excitatory amino acid and dopamine receptors through the generation of second messengers. Individual paralogs, splice variants and multiple forms of PLA(2) may have unique enzymatic properties, tissue and subcellular localizations and role in various physiological and pathological situations, hence tight regulation of all PLA(2) isoforms is essential for normal brain function. Quantitative RT-PCR analyses show significantly higher relative level of expression of iPLA(2) than cPLA(2) in all regions of the rat brain. Upregulation of the cPLA(2) family is involved in degradation of neural membrane phospholipids and generation of arachidonic acid-derived lipid metabolites that have been implicated in nociception, neuroinflammation, oxidative stress and neurodegeneration. In contrast, studies using a selective iPLA(2) inhibitor, bromoenol lactone, or antisense oligonucleotide indicate that iPLA(2) is an important "housekeeping" enzyme under basal conditions, whose activity is required for the prevention of vacuous chewing movements, a rodent model for tardive dyskinesia, and deficits in the prepulse inhibition of the auditory startle reflex, a common finding in schizophrenia. These studies support the view that PLA(2) activity may not only play a crucial role in neurodegeneration but depending on the isoform, could also be essential in prevention of neuropsychiatric diseases. The findings could open new doors for understanding and treatment of neurodegenerative and neuropsychiatric diseases. PMID- 20586720 TI - Organometallic complexes: new tools for chemotherapy. AB - The importance of organometallics can be noticed by their presence in all life organisms. The most known natural organometallic molecule is vitamin B12, a porphyrin containing a cobalt atom, useful for several enzymatic transformations. Based on the remarkable properties of this class of compounds, a new area of medicinal research was developed. Gerard Jaouen was the first to introduce the term of "bioorganometallic chemistry" in 1985 although the first organometallic therapeutical was Salvarsan(r), discovered by Paul Ehrlich (Nobel Prize in Medicine in 1908). Bioorganometallic chemistry consists of the synthesis and the study of organometallic complexes, complexes with at least one metal-carbon bond, in a biological and medicinal interest. This field of research was accentuated by the discovery of the ferrocene in 1951 by Pauson and Kealy, confirmed in 1952 by Wilkinson (Nobel Prize in 1973). Today, bioorganometallic chemistry includes 5 main domains: (1) organometallic therapeuticals, (2) toxicology and environment, (3) molecular recognition in aqueous phases, (4) enzymes, proteins and peptides, (5) bioanalysis and pharmaceutical sensors. In this review, we focused on organometallic therapeuticals. The exceptional properties of organometallics are first described and then, an overview on the main organometallic complexes used for drug design is presented. This review gives an idea how organometallics can be used for the rational design of new drugs. PMID- 20586721 TI - Targeting death receptors to fight cancer: from biological rational to clinical implementation. AB - Considering that most currently available chemotherapeutic drugs work by inducing cell apoptosis, it is not surprising that many expectations in cancer research come from the therapeutic exploitation of the naturally occurring death pathways. Receptor mediated apoptosis depends upon the engagement of specific ligands with their respective membrane receptors and - within the frame of complex regulatory networks - modulates some key physiological and pathological processes such as lymphocyte survival, inflammation and infectious diseases. A pivotal observation was that some of these pathways may be over activated in cancer under particular circumstances, which opened the avenue for tumor-specific therapeutic interventions. Although one death-related ligand (e.g., tumor necrosis factor, TNF) is currently the basis of effective anticancer regimens in the clinical setting, the systemic toxicity is hampering its wide therapeutic exploitation. However, strategies to split the therapeutic from the toxic TNF activity are being devised. Furthermore, other death receptor pathways (e.g., Fas/FasL, TRAIL/TRAIL receptor) are being intensively investigated in order to therapeutically exploit their activity against cancer. This article summarizes the current knowledge on the molecular features of death receptor pathways that make them an attractive target for anticancer therapeutics. In addition, the results so far obtained in the clinical oncology setting as well as the issues to be faced while interfering with these pathways for therapeutic purposes will be overviewed. PMID- 20586722 TI - The scatter factor signaling pathways as therapeutic associated target in cancer treatment. AB - Receptor tyrosine kinases (RTKs) are key regulators of critical cellular processes such as proliferation, differentiation, neo-vascularization, and tissue repair. In addition to their importance in the regulation of normal physiology, aberrant expression of certain RTKs has also been associated to the development and progression of many types of cancer. c-Met and RON are two RTKs with closely related sequences, structural homology, and similar functional properties. Both these receptors, once activated by their respective ligands, the Hepatocyte Growth Factor/Scatter Factor (HGF/SF1) and the Macrophage Stimulating Protein/Scatter Factor 2 (MSP/SF2), can induce cell migration, invasion and proliferation. Soon after its discovery in the mid-1980s, c-Met attracted a great interest because of its role in modulating cell motility. Moreover, the causal role for c-Met activating mutations in human cancer propelled an intensive drug discovery effort throughout academic institutions and pharmaceutical companies. While c-Met is now a well-accepted target for anticancer drug design, less is known about the role of RON in cancer and less has been done to target this receptor. In this review we will discuss the biological relevance of c-Met and RON, their deregulation in human cancers and the progress, so far, in identifying c-Met and RON signaling inhibitors. Finally, we will focus on the development of therapeutic strategies and drug efficacy studies based on interfering the scatter factor signaling pathways. PMID- 20586724 TI - The next generation of drug delivery system and diagnostics based on Micro Electro-Mechanical-System (MEMS) and nanotechnology. PMID- 20586725 TI - Intrinsic properties and external factors determine the differentiation bias of human embryonic stem cell lines. AB - A major goal of human embryonic stem cell (hESC) research is to regulate differentiation through external means to generate specific cell types with high purity for regenerative medicine applications. Although all hESC lines express pluripotency-associated genes, their differentiation ability to various lineages differs considerably. We have compared spontaneous differentiation propensity of the two hESC lines, RelicellhES1 and BG01. Spontaneous differentiation of hESC lines grown in different media conditions was followed by differentiation using two methods. Kinetic data generated by real-time gene expression studies for differentiated cell types were analyzed, and confirmed at protein levels. Both cell lines showed upregulation of genes associated with the 3 germ layers, although stark contrast was evident in the magnitude of upregulation of lineage specific genes. A distinct difference was also found in the rate at which the pluripoteny factors, Oct-4 and Nanog, were downregulated during differentiation. Once differentiation was initiated, both Oct-4 and Nanog gene expression was drastically reduced in RelicellhES1, whereas a gradual decrease was observed in BG01. A clear trend is seen in RelicellhES1 to differentiate into neuroectodermal and mesenchymal lineages, whereas BG01 cells are more prone to mesoderm and endoderm development. In addition, suspension versus plated methods of cell culture significantly influenced the outcome of differentiation of certain types of cells. Results obtained by spontaneous differentiation of hESCs were also amplified by induced differentiation. Thus, differential rates of downregulation of pluripotency markers along with culture conditions seem to play an important role in determining the developmental bias of human ES cell lines. PMID- 20586723 TI - Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry. AB - Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents. PMID- 20586726 TI - Versatility in the acquisition of energy and carbon sources by the Apicomplexa. AB - Members of the phylum Apicomplexa are motile and rapidly dividing intracellular parasites, able to occupy a large spectrum of niches by infecting diverse hosts and invading various cell types. As obligate intracellular parasites, most apicomplexans only survive for a short period extracellularly, and, during this time, have a high energy demand to power gliding motility and invasion into new host cells. Similarly, these fast-replicating intracellular parasites are critically dependent on host-cell nutrients as energy and carbon sources, noticeably for the extensive membrane biogenesis imposed during growth and division. To access host-cell metabolites, the apicomplexans Toxoplasma gondii and Plasmodium falciparum have evolved strategies that exquisitely reflect adaptation to their respective niches. In the present review, we summarize and compare some recent findings regarding the energetic metabolism and carbon sources used by these two genetically tractable apicomplexans during host-cell invasion and intracellular growth and replication. PMID- 20586727 TI - Cost of disorders of the brain in Norway. AB - BACKGROUND: Little is known about the cost of neurological disorders in Norway. OBJECTIVES: To estimate the cost of disorders of the brain, including the main psychiatric, neurological and neurosurgical conditions in Norway. METHODS: Most of the data are extrapolations from a large European cost study that collected the best available epidemiological and health economical evidence for the year 2004. Some epidemiological data are available from Norway, but very little on costs. RESULTS: Brain disorders seemed to affect 1.5 million Norwegians in 2004, and the total cost amounted to 5.8 billion Euros. The most prevalent disorders are anxiety disorders and migraine, and the most costly are affective disorders, addiction and dementia. Migraine is the most costly of the purely neurological conditions, followed by stroke, epilepsy and Parkinson's disease. The indirect costs account for more than half of the total costs. DISCUSSION: Although the different brain disorders are very dissimilar in appearance, from health economic and public health perspectives, it is relevant to view them as a whole, since many of them share important pathophysiological mechanisms. This means that new insights into one disorder can have relevance for many other disorders. CONCLUSION: As a result of the high impact on individuals and society, more resources should be allocated to treatment and research into brain disorders. PMID- 20586728 TI - Cerebrospinal fluid opening pressure measurements in acute headache patients and in patients with either chronic or no pain. AB - OBJECTIVE: To observe cerebrospinal fluid opening pressure (CSFOP) in different clinical settings and in patients with acute, chronic and no pain and to observe possible differences because of age and sex. METHOD: In this prospective study, CSFOP was measured in lumbar puncture in three different settings of clinical investigations; patients with acute headache investigated for subarachnoidal haemorrhage (n = 222), patients with sciatica undergoing myelography (n = 61), and patients in an outpatient neurological clinic (n = 65). RESULTS: The mean CSFOP in cm H(2)O was 17.3 for the myelography patients, 19.1 for the outpatients, 19.3 for the primary headache patients and 22.4 for the patients with secondary headache. Large proportions of patients in all groups had CSFOP above 20 cm H(2)O. The female patients in all groups had lower mean CSFOP than the male patients. CONCLUSION: The CSFOP levels found in clinical practice among patients without intracranial lesions or infectious conditions were broader than expected. Measurement of CSFOP is of limited value as diagnostic procedure if not closely linked to clinical symptoms and finds. PMID- 20586729 TI - Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients. AB - OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease of neuromuscular synapses, characterized by muscular weakness and reduced endurance. Remission can be obtained in many patients. However, some of these patients complain of fatigue. The aim of this study was to assess exercise capacity and lung function in well-regulated MG patients. PATIENTS AND METHODS: Ten otherwise healthy MG patients and 10 matched controls underwent dynamic spirometry, and a ramped symptom-limited bicycle exercise test. Spirometric variables included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV). Exercise variables included maximal oxygen uptake (VO(2) max), anaerobic threshold (VO(2) AT) maximum work load (W), maximum ventilation (VE max), and limiting symptom. RESULTS: Myasthenia gravis patients had significantly lower FEV1/FVC ratio than controls. This was more marked in patients on acetylcholine esterase inhibitors. On the contrary, patients not using acetylcholine esterase inhibitors had a significantly lower exercise endurance time. CONCLUSION: Well-regulated MG patients, especially those using pyridostigmine, tend to have an airway obstruction. The modest airway limitation might be a contributing factor to their fatigue. Patients who are not using acetylcholinesterase inhibitor seem to have diminished exercise endurance in spite of their clinically complete remission. PMID- 20586730 TI - Psychiatric comorbidity and use of psychotropic drugs in epilepsy patients. AB - OBJECTIVES: Although epilepsy is associated with a high rate of psychiatric comorbidity, clinicians may withhold treatment with psychotropic drugs for fear of worsening seizures. We have assessed the occurrence of psychiatric disorders in a cohort of epilepsy patients and used the results to discuss this important topic. MATERIAL AND METHODS: Based on a questionnaire we made a survey of psychiatric symptoms in 167 adult patients referred to a tertial epilepsy center. The mean age was 42 years, and 72% had active epilepsy. RESULTS: Forty three patients (26%) had a psychiatric disorder, and 22 patients (13%) used psychotropic drugs. The most frequent diagnoses were mood disorders and anxiety. CONCLUSIONS: Compared with the general population, people with epilepsy have an increased risk of developing psychiatric disorders. Patients with uncontrolled seizures are most vulnerable. These disorders appear to be under-diagnosed and under-treated, and the fear that psychotropic drugs can cause seizure exacerbation is probably overstated. PMID- 20586731 TI - Moderate wine consumption is associated with better cognitive test results: a 7 year follow up of 5033 subjects in the Tromso Study. AB - BACKGROUND: The impact of moderate alcohol consumption on cognitive function and dementia is unclear. We examined the relationship between consumption of different alcoholic beverages and cognitive function in a large population-based study. METHODS: Subjects were 5033 stroke-free men and women who participated in a longitudinal population-based study in Tromso, Norway. Alcohol consumption and other cardiovascular risk factors were measured at baseline and cognitive function was assessed after 7 years follow up with verbal memory test, digit symbol coding test and tapping test. RESULTS: Moderate wine consumption was independently associated with better performance on all cognitive tests in both men and women. There was no consistent association between consumption of beer and spirits and cognitive test results. Alcohol abstention was associated with lower cognitive performance in women. CONCLUSIONS: Light-to-moderate wine consumption was associated with better performance on cognitive tests after 7 years follow up. PMID- 20586732 TI - Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine. AB - OBJECTIVES: The aim of the study was to investigate risk factors for cardiovascular disease in patients with epilepsy using the new antiepileptic drug levetiracetam (LEV), compared with patients taking carbamazepine (CBZ) or lamotrigine (LTG). METHODS: Two hundred and twelve patients and 80 controls (age: 18-45 years) of both genders were included. The patients had been treated with either LEV (n = 52), CBZ (n = 87) or LTG (n = 73) monotherapy for at least 6 months. Total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured. Smoking, drinking habits and physical activity were recorded and body mass index (BMI) was calculated. RESULTS: Neither LEV nor LTG altered TC, LDL or HDL. Both men and women using CBZ had higher TC, HDL and LDL than controls. LDL/HDL and TC/HDL ratios were unchanged. Women on CBZ and LTG had a greater BMI when compared with the control group. Patients with epilepsy recorded less physical activity and lower alcohol use than the controls. CONCLUSIONS: Neither LEV nor LTG affected blood lipid levels, while patients treated with CBZ have higher cholesterol, HDL and LDL than controls. The patients were less physically active, and women on CBZ and LTG had higher BMI. PMID- 20586733 TI - Depression predicts unfavourable functional outcome and higher mortality in stroke patients: the Bergen Stroke Study. AB - OBJECTIVE: To assess the influence of depression prior to stroke (PD) on stroke severity on admittance, functional outcome (short- and long-term), mortality, and long-term depression (PSD). METHODS: Consecutive acute stroke patients were screened for PD. The National Institute of Health Stroke Scale score was obtained on admission. Short-term functional state was registered by the modified Rankin scale and on long-term functional outcome by the Barthel Index. PSD was defined as depression subscale of the hospital anxiety and depression scale (HADSD) >or=11. HADSD and Barthel Index were obtained by postal questionnaire. Survival analyses were performed. RESULTS: Among 771 patients 21.7% had PD. Among 376 patients returning the questionnaire, 8.8% were depressed. On logistic regression analyses severity of stroke on admission, short-term, and long-term functional outcome were independently associated with PD. Logistic regression showed PSD to be independently associated with PD and being unmarried. Cox regression analyses showed that both PD and PSD were associated with high long-term mortality. CONCLUSIONS: This study has identified several factors associated with PSD. PD predicts more severe stroke on admittance and less functional improvement both in the short- and the long-term. Both PD and PSD predict higher long-term mortality. PMID- 20586734 TI - Delirium in acute stroke--prevalence and risk factors. AB - BACKGROUND: Delirium is frequently seen as a major complication among elderly stroke patients. Few studies have prospectively studied delirium as a complication of acute stroke. In these studies, the results are conflicting regarding risk factors and estimated prevalence. The aims of the present study are to assess the prevalence of delirium in patients with acute stroke treated in an acute Stroke Unit, identify characteristics of patients with delirium and important factors associated with the development of delirium. METHODS: We conducted a prospective study of patients with delirium and acute stroke consecutively admitted to a Stroke Unit. The diagnosis of delirium was based on Confusion Assessment Method (CAM). CAM is devised from DSM-III-R criteria based on the diagnosis of delirium, and is a simple test with high sensitivity and specificity. RESULTS: One hundred and seventy-eight patients with a diagnosis of stroke were eligible for the study. The prevalence of delirium in acute stroke in our study was 10% (18 of 178 patients). Patients with delirium had significantly longer length of stay in the Stroke Unit (12.3 vs 8.5 days, P < 0.004). Prestroke dementia [odds ratio (OR) 18.7], hemianopsia (OR 12.3), apraxia (OR 11.0), higher age (OR 5.5) and infection (UTI or pneumonia) (OR 4.9) during in-hospital stay were associated with increased risk of delirium. CONCLUSION: One of 10 stroke patients had delirium. This is the lowest prevalence of delirium shown in acute stroke patients. In our study, all patients were treated in a Stroke Unit. A Stroke Unit like the Scandinavian model may be beneficial in preventing delirium. PMID- 20586735 TI - Benign multiple sclerosis: a need for a consensus. AB - OBJECTIVES: To investigate the impact of different definitions on the frequency of benign multiple sclerosis (MS) in patients with a long follow-up, and to study the presence of non-motor symptoms and employment across the definitions. MATERIALS AND METHODS: All patients alive (n = 188) with disease onset during 1976-1986 in Hordaland County, Norway, were clinically examined including the Expanded Disability Status Scale (EDSS) in 2003. Non-motor symptoms which included depression, cognitive impairment, fatigue and pain, and employment status were also registered. Three definitions of benign MS were used based on the following EDSS cut-off values: 2.0, 3.0 and 4.0. Two additional definitions were added using an EDSS 8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. METHODS: Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose-response for quinine taste preference in IAA and continuous-access animals was determined. RESULTS: Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in animals with continuous access to alcohol. Finally, no changes in quinine taste preference after 3 to 4 months IAA or continuous access to alcohol were observed. CONCLUSIONS: We have developed a novel and technically simple hybrid operant/IAA model in which quinine-resistant motivation for alcohol is evident after an experimentally tractable period of time (3 to 4 months vs. 8 months). Quinine dramatically reduced sucrose and water intake by IAA rats, indicating that continued responding for alcohol in IAA rats despite adulteration with the normally aversive quinine might reflect maladaptive or compulsive motivation for alcohol. This model could facilitate identification of novel therapeutic interventions for pathological alcohol seeking in humans. PMID- 20586758 TI - Withdrawal severity after chronic intermittent ethanol in inbred mouse strains. AB - BACKGROUND: To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. METHODS: Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. RESULTS: Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 +/- 0.02 mg/ml and we restricted the range of this value to 1.00-2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 +/- 0.1 mg/ml) and high dose (1.71 +/- 0.02 mg/ml). After the third inhalation exposure, ethanol exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. CONCLUSION: The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses. PMID- 20586759 TI - Differential changes in MAP kinases, histone modifications, and liver injury in rats acutely treated with ethanol. AB - BACKGROUND: Acute ethanol is known to affect cells and organs but the underlying molecular mechanisms are poorly explored. Recent developments highlight the potential importance of mitogen-activated protein kinases, MAPKs (i.e., ERK1/2, p38, and JNK1/2) signaling, and histone modifications (i.e., acetylation, methylation, and phosphorylation) in the actions of ethanol in hepatocytes. We have therefore investigated significance of these molecular steps in vivo using a model in which rats were acutely administered ethanol intraperitoneally (IP). METHODS: Ethanol was administered IP (3.5 gm/kg body weight) to 12-week-old male Sprague-Dawley rats. Liver was subsequently removed at 1 and 4 hours. Serum was used for alcohol and ALT assays. At the time of the removal of liver, small portions of each liver were formalin-fixed and stained with hematoxylin and eosin (H&E) and used for light microscopy. Western blot analysis was carried out with specific primary antibodies for various parameters. RESULTS: There were clear differences at 1 and 4 hours in blood ethanol, ALT, steatosis, and cleaved caspase 3. Apoptosis at 1 hour was followed by necrosis at 4 hours. Acute alcohol elicited a marked increase in the phosphorylation of ERK1/2 and moderate increases in the phosphorylation of p38 MAPK and JNK. Temporally different phosphorylation of histone H3 at ser-10 and ser-28 occurred and acetylation of histone H3 at lys 9 increased progressively. CONCLUSIONS: There were distinct differences in the behavior of the activation of the 3 MAP kinases and histone modifications after acute short exposure of liver to ethanol in vivo. Although all 3 MAPKs were rapidly activated at 1 hour, the necrosis, occurring at 4 hours, correlated to sustained activation of ERK1/2. Transient activation of p38 is associated with rapid phosphorylation of histone H3, whereas prolonged activation of ERK1/2 is correlated to persistent histone H3 acetylation. PMID- 20586760 TI - Quercetin and ethanol attenuate the progression of atherosclerotic plaques with concomitant up regulation of paraoxonase1 (PON1) gene expression and PON1 activity in LDLR-/- mice. AB - BACKGROUND: As moderate wine drinking is atheroprotective, it is clinically relevant to elucidate its possible mechanism/s of action/s. Our objective is to demonstrate the potential benefits of the wine components, quercetin and ethanol, on the development of aortic plaques with parallel changes in antiatherogenic factors. METHODS AND RESULTS: The effects of quercetin and ethanol on the development of aortic atherosclerotic lesions, liver PON1 gene expression, and serum PON1 activity were measured in LDLR(-/-) mice on an atherogenic diet for 4 and 8 weeks. Depending on the duration and dosage of these modulators, 12.5 to 25 mg/dl quercetin (12.5Q to 25Q) and 18 to 25% ethanol, the magnitude of decreases in aortic lesions caused by moderate ethanol and quercetin ranged from 20 to 70% (p < 0.05 to p < 0.001) based on ultrasound biomicroscopy (UBM) analyses, and from 18 to 61% (p < 0.05 to p < 0.001) based on morphometric analyses. The composite plot of all the UBM and morphometric data showed significant correlation between these 2 methods (p = 0.0001, Pearson r = 0.79 for 4-week treatment; p = 0.000004, Pearson r = 0.84 for 8-week treatment). Concomitantly, 4 week treatments with 12.5Q and 18% ethanol up regulated liver PON1 mRNA by 41% (p < 0.05) and 37% (p < 0.05), respectively, accompanied by 92% (p < 0.001) and 61% (p < 0.001) increases in serum PON1 activity, respectively. The corresponding values after 8-week treatment with 12.5Q and 18% ethanol were 23% (p < 0.05) and 40% (p < 0.02) with respect to the up regulation of liver PON1 mRNA expression, while the stimulations of serum PON1 activity were 75% (p < 0.001) and 90% (p < 0.001), respectively. CONCLUSIONS: Based on these findings, we conclude that quercetin and moderate ethanol significantly inhibit the progression of atherosclerosis by up regulating the hepatic expression of the antiatherogenic gene, PON1, with concomitant increased serum PON1 activity. PMID- 20586761 TI - Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons. AB - BACKGROUND: The current therapies for alcohol abuse disorders are not effective in all patients, and continued development of pharmacotherapies is needed. One approach that has generated recent interest is the antagonism of ghrelin receptors. Ghrelin is a gut-derived peptide important in energy homeostasis and regulation of hunger. Recent studies have implicated ghrelin in alcoholism, showing altered plasma ghrelin levels in alcoholic patients as well as reduced intakes of alcohol in ghrelin receptor knockout mice and in mice treated with ghrelin receptor antagonists. The aim of this study was to determine the neuroanatomical locus/loci of the effect of ghrelin receptor antagonism on alcohol consumption using the ghrelin receptor antagonist, D-Lys3-GHRP-6. METHODS: In Experiment 1, male C57BL/6J mice were injected with saline 3 hours into the dark cycle and allowed access to 15% (v/v) ethanol or water for 2 hours in a 2-bottle choice experiment. On test day, the mice were injected with either saline or 400 nmol of the ghrelin receptor antagonist, D-Lys3-GHRP-6, and allowed to drink 15% ethanol or water for 4 hours. The preference for alcohol and alcohol intake were determined. In Experiment 2, the same procedure was followed as in Experiment 1 but mice were only allowed access to a single bottle of 20% ethanol (v/v), and alcohol intake was determined. Blood ethanol levels were analyzed, and immunohistochemistry for c-Fos was carried out to investigate changes in neural activity. To further elucidate the mechanism by which D-Lys3-GHRP-6 affects alcohol intake, in Experiment 3, the effect of D-Lys3-GHRP-6 on the neural activation induced by intraperitoneal ethanol was investigated. For the c-Fos studies, brain regions containing ghrelin receptors were analyzed, i.e. the perioculomotor urocortin population of neurons (pIIIu), the ventral tegmental area (VTA), and the arcuate nucleus (Arc). In Experiment 4, to test if blood ethanol concentrations were affected by D-Lys3-GHRP-6, blood samples were taken at 2 time-points after D-Lys3-GHRP-6 pretreatment and systemic ethanol administration. RESULTS: In Experiment 1, D-Lys3-GHRP-6 reduced preference to alcohol and in a follow-up experiment (Experiment 2) also dramatically reduced alcohol intake when compared to saline-treated mice. The resulting blood ethanol concentrations were lower in mice treated with the ghrelin receptor antagonist. Immunohistochemistry for c-Fos showed fewer immunopositive cells in the pIIIu of the antagonist-treated mice but no difference was seen in the VTA or Arc. In Experiment 3, D-Lys3-GHRP-6 reduced the induction of c-Fos by intraperitoneal ethanol in the pIIIu but had no effect in the VTA. In the Arc, there was a significant increase in the number of c-Fos immunopositive cells after D-Lys3 GHRP-6 administration, but the antagonist had no effect on ethanol-induced expression of c-Fos. D-Lys3-GHRP-6-pretreatment also did not affect the blood ethanol concentrations observed after a systemic injection of ethanol when compared to saline-pretreated mice (Experiment 4). CONCLUSIONS: These findings indicate that the action of ghrelin on the regulation of alcohol consumption may occur via the pIIIu. PMID- 20586762 TI - Genetic variation of the ghrelin signaling system in females with severe alcohol dependence. AB - INTRODUCTION: Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). METHODS: Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. RESULTS: We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. CONCLUSION: Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI. PMID- 20586764 TI - Comprehending ecological and economic sustainability: comparative analysis of stability principles in the biosphere and free market economy. AB - The global environmental imperative demands urgent actions on ecological stabilization, yet the global scale of such actions is persistently insufficient. This calls for investigating why the world economy appears to be so fearful of any potential environmental expenditure. Using the formalism of Lyapunov potential function it is shown that the stability principles for biomass in the ecosystem and for employment in economics are mathematically similar. The ecosystem has a stable and unstable stationary state with high (forest) and low (grasslands) biomass, respectively. In economics, there is a stable stationary state with high employment in mass production of conventional goods sold at low cost price, and an unstable stationary state with lower employment in production of novel products of technological progress sold at higher prices. An additional stable state is described for economics with very low employment in production of life essentials, such as energy and raw materials that are sold at greatly inflated prices. In this state the civilization pays 10% of global GDP for energy produced by a negligible minority of the working population (currently approximately 0.2%) and sold at prices exceeding the cost price by 40 times, a state when any extra expenditures of whatever nature appear intolerable. The reason lies in the fundamental shortcoming of economic theory, which allows for economic ownership over energy sources. This is shown to be equivalent to equating measurable variables of different dimensions (stores and fluxes), which leads to effective violation of the laws of energy and matter conservation in modern economics. PMID- 20586765 TI - Modeling the greenhouse gas budget of straw returning in China: feasibility of mitigation and countermeasures. AB - Straw returning is considered to be one of the most promising carbon sequestration measures in China's cropland. A compound model, namely "Straw Returning and Burning Model-Expansion" (SRBME), was built to estimate the net mitigation potential, economic benefits, and air pollutant reduction of straw returning. Three scenarios, that is, baseline, "full popularization of straw returning (FP)," and "full popularization of straw returning and precision fertilization (FP + P)," were set to reflect popularization of straw returning. The results of the SRBME indicated that (1) compared with the soil carbon sequestration of 13.37 Tg/yr, the net mitigation potentials, which were 6.328 Tg/yr for the FP scenario and 9.179 Tg/yr for the FP + P scenario, had different trends when the full budget of the greenhouse gases was considered; (2) when the feasibility in connection with greenhouse gas (GHG) mitigation, economic benefits, and environmental benefits was taken into consideration, straw returning was feasible in 15 provinces in the FP scenario, with a total net mitigation potential of 7.192 TgCe/yr and the total benefits of CNY 1.473 billion (USD 216.6 million); (3) in the FP + P scenario, with the implementation of precision fertilization, straw returning was feasible in 26 provinces with a total net mitigation potential of 10.39 TgCe/yr and the total benefits of CNY 5.466 billion (USD 803.8 million); (4) any extent of change in the treatment of straw from being burnt to being returned would contribute to air pollution reduction; (5) some countermeasures, such as CH(4) reduction in rice paddies, precision fertilization, financial support, education and propaganda, would promote the feasibility of straw returning as a mitigation measure. PMID- 20586766 TI - Conjugate ecopolis planning: balancing ecoservice and human well-being in Beijing. AB - On the basis of the ancient Chinese human ecological principles, conjugate ecological planning is a kind of social-economic-natural complex ecosystem planning to balance and/or compromise the relationship between environmental and economic development. Eight conjugate planning issues were investigated. It was used in the ecological planning research for Beijing Master Plan revision. The results of East Beijing land-use scenario were shown and ecoservice-based land management strategies were proposed. The executive summary of conjugate ecological planning of Beijing urban ecosystem was introduced in the end. PMID- 20586767 TI - Pursuing sustainable industrial development through the ecoindustrial parks: three case studies of China. AB - As one branch of industrial ecology, the ecoindustrial park (EIP) concept is being accepted and implemented in many parts of the world. In order to pursue a sustainable industrial development, China's government is forging this concept into a new strategy of industrial development and regional practices. This article aims to depict a picture of current China's experiences on EIP. It first presents two stages of EIP development at national level. Then more details at individual level are provided by three cases studies, that is, Dafeng, Lubei, and Nanhai, in which three points are addressed: (1) the industrial and environmental backgrounds of EIP projects; (2) specific resource sharing; and (3) benefits and challenges in these projects. The case studies show that the government acts as a key role player, facilitating multiple functions in the development of EIP projects. The case studies also suggest that many factors including holistic, economic, social, and technical aspects need to be taken into account to develop a successful EIP project. PMID- 20586768 TI - A sustainable landscape ecosystem design: a case study. AB - Landscape planning is clearly ecologically and socially relevant. Concern about sustainability between human and environment is now a driving paradigm for this professional. However, the explosion of the sustainable landscape in China is a very recent phenomenon. What is the sustainable landscape? How is this realized in practice? In this article, on the basis of the reviews of history and perplexities of Chinese landscape and nature analysis of sustainable landscape, the ecothinking model, an implemental tool for sustainable landscape, was developed, which applies ecothinking in vision, culture, conservation and development of site, and the process of public participation for a harmonious relationship between human and environment. And a case study of the south entrance of TongNiuling Scenic Area was carried out, in which the most optimum scenario was chosen from among three models according to the ecothinking model, to illustrate the construction of the ecothinking model and how to achieve a sustainable landscape. PMID- 20586769 TI - Characterizing urbanization, and agricultural and conservation land-use change in Riverside County, California, USA. AB - Monitoring trends in urbanization and land use related to population growth and changing social and economic conditions is an important tool for developing in land use and habitat conservation policy. We analyzed urbanization and agricultural land-use change in Riverside County, California from 1984 to 2002, comparing maps every two years on the basis of aerial photographs. Matrix analysis combined with information theory was applied to study land type conversion. Results showed that the total area of "Urban and Built-Up Land" increased the most whereas total area of "Prime Farmland" decreased most. Land use characterized as "Grazing Land,""Farmland of Local Importance," and "Farmland of Statewide Importance" also decreased. Mean patch size also decreased for "Grazing Land,""Water Area,""Other Land," and "Prime Farmland." The diversity of land types decreased dramatically after 1992. Urbanization patterns were different among three city groups (Riverside City, Coachella Valley, and Blythe), indicating the different times for "leapfrog" development in the three areas. Furthermore, the unpredictability and change in composition of land use increased after 1996 due to intensified urbanization. If the current driving forces continue, our model projects that in 2020 the area of "Urban and Built-Up Land" may increase between 25% and 39% in comparison with 2002. Percentages of most agricultural land types are projected to decrease, especially "Farmland of Local Importance,""Prime Farmland," and "Farmland of Statewide Importance." If the county's goal is to preserve agricultural lands and natural biodiversity, while maintaining sustainable development, current land-use policies and practices should be changed. This study demonstrates new useful methods for monitoring and detection of change of land-use processes. PMID- 20586770 TI - Complexity, collective effects, and modeling of ecosystems: formation, function, and stability. AB - We discuss the relevance of studying ecology within the framework of Complexity Science from a statistical mechanics approach. Ecology is concerned with understanding how systems level properties emerge out of the multitude of interactions among large numbers of components, leading to ecosystems that possess the prototypical characteristics of complex systems. We argue that statistical mechanics is at present the best methodology available to obtain a quantitative description of complex systems, and that ecology is in urgent need of "integrative" approaches that are quantitative and nonstationary. We describe examples where combining statistical mechanics and ecology has led to improved ecological modeling and, at the same time, broadened the scope of statistical mechanics. PMID- 20586771 TI - The role of fluctuating resource supply in a habitat maintained by the competition-colonization trade-off. AB - An exotic species can be a superior colonizer but inferior resource competitor relative to native species. Such species can spatially coexist for an extended period of time in a community maintained via competition-colonization (CC) trade offs. Whether fluctuations in resource supply allow such exotic species to successfully invade and displace the native species or hold the coexistence is not previously explored, and it is the focus of this study. In this article, we model propagule-limited spatial competition explicitly linked with resource competition within the framework of the classic CC-model, while time-dependent fluctuations in resource supply are considered in a sinusoidal function. The model predicts that if the amplitude of the fluctuations is greater than the average resource supply rate, there exist a range of values of fluctuation frequency that can allow the exotic species to successfully invade the habitat and to reduce the extent of native species. On the other hand, if the fluctuation amplitude is less than the average resource supply rate, such exotic species can coexist with the native species, independent of fluctuation frequencies. In addition, we found that at a constant resource supply rate, the exotic species can stably coexist with the native species at competitive equilibrium. PMID- 20586763 TI - Laboratory models available to study alcohol-induced organ damage and immune variations: choosing the appropriate model. AB - The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals. This article summarizes the various laboratory models of alcohol abuse that are currently available and are used to study the mechanisms by which alcohol abuse induces organ damage and immune defects. The strengths and weaknesses of each of the models are discussed. Integrated into the review are the presentations that were made in the symposium "Methods of Ethanol Application in Alcohol Model-How Long is Long Enough" at the joint 2008 Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) meeting, Washington, DC, emphasizing the importance not only of selecting the most appropriate laboratory alcohol model to address the specific goals of a project but also of ensuring that the findings can be extrapolated to alcohol-induced diseases in humans. PMID- 20586772 TI - Relationship between species diversity and ecotope diversity. AB - The relationship between species diversity and ecotope diversity has long been debated. But these debates seem meaningless because most of them were based on different definitions. In this paper, diversity has two components: richness based on the total number and evenness based on the relative abundance. Species diversity is distinguished into individual-counting diversity and biomass-based diversity. Ecotope diversity is divided into individual ecotope-counting diversity and ecotope-area based diversity. Under this definition, we make a comprehensive investigation into Dongzhi tableland of Loess Plateau by cooperating with local technicians. We find that individual-counting diversity is significantly correlated with biomass-based diversity in grassland ecosystems; individual ecotope-counting diversity and ecotope-area based diversity have a significant correlation. Therefore, it is unnecessary to divide species diversity into individual-counting diversity and biomass-based diversity in grassland ecosystems and to distinguish ecotope diversity into individual ecotope-counting and ecotope-area based diversity for the issues that have no special requirement for accuracy. But the analyses of the investigation data demonstrate that species diversity has no significant correlation with ecotope diversity. PMID- 20586773 TI - Effects of biodiversity and plant community composition on productivity in semiarid grasslands of Hulunbeir, Inner Mongolia, China. AB - Many recent studies have focused on the relationship between biodiversity and ecosystem functioning, such as investigations into the productivity of experimental plant communities. One of the central issues affecting the functioning of ecosystems is the diversity of resident species richness and the composition of the plant community. However, one challenge to experimental studies is that results from artificial ecosystems may have little value for predicting loss of diversity and function degradation in natural ecosystems. Thus, recent studies have focused more on investigations of natural ecosystems; these studies have found that species diversity and ecosystem productivity usually correlate with various abiotic factors including environmental effects, such as soil nutrition and precipitation, as well as anthropic activities, such as grazing and agricultural yield. In this study, we aimed to test the validity of biotic factors reported in experimental studies to be major factors affecting the productivity of ecosystems, and then to determine whether the relationship between biodiversity and ecosystem function is confounded by environmental factors. We investigated the effects of plant biodiversity and community composition on ecosystem function (productivity) in semiarid grassland in Inner Mongolia, China that contained three vegetation types: arid steppe, steppe, and meadow steppe. Our results show that both diversity and community composition significantly affect productivity and are better predictors of productivity than environmental factors, such as soil conditions. Our findings are consistent with the assumptions of niche complementarity. This study suggests that both biodiversity and community composition are important biotic factors in the functioning of ecosystems located in semiarid grasslands. In addition, environmental parameters, such as soil conditions influence productivity indirectly by affecting both biotic factors at the same time. PMID- 20586774 TI - Effect of long-term fertilization on total soil arsenic in China. AB - To assess the effects of long-term fertilization on arsenic (As) accumulation in soils and crops with different agricultural practices, five experimental stations (Changshu, Taoyuan, Hailun, Fengqiu, and Qiyang) with long-term fertilization practices, representing five typical soils of China, were selected to investigate the soil As concentrations. Results indicated that the geological source, that is, parent materials, played a dominant role in determining the soil As concentrations. Long-term application of manure and phosphorus fertilizers led to a decrease of As concentration in the surface paddy soil at Taoyuan, while the effects of fertilization on As concentration in other samples were minimal. In addition, other agricultural practices, such as the removal of crop biomass, reduced the As concentrations in the surface soils with low levels of soil As (Fengqiu, Changshu, and Taoyuan). In the upland soils with higher As concentrations, wheat may have risk to human health through food-chain and maize can be considered as a favorable crop. PMID- 20586775 TI - Soil fertility controls the size-specific distribution of eukaryotes. AB - The large range of body-mass values of soil organisms provides a tool to assess the organization of soil ecological communities. Relationships between log transformed body mass M and log-transformed numerical abundance N of all eukaryotes occurring under organic pastures, mature grasslands, and seminatural heathlands in the Netherlands were investigated. The observed allometry of (M,N) assemblages of below-ground communities strongly reflects the availability of primary macronutrients and essential micronutrients. This log-linear model describes the continuous variation in the allometric slope of animals and fungi along an increasing soil fertility gradient. The aggregate contribution of small invertebrates (M < 1 microg) to the entire faunal community is highest under nutrient deficiency and causes shifts in the mass-abundance relationships. The phosphorus concentration in the soil explains 72% of these shifts but the nitrogen concentration explains only 36%, with copper and zinc as intermediate predictors (59% and 49%, respectively). Empirical evidence supports common responses of invertebrates to the rates of resource supply and, possibly, to the above-ground primary production of ecosystems. PMID- 20586776 TI - Changes in the soil microbial community with a pine plantation restoration in a dry valley of the upper reaches of the Minjiang River, southwest China. AB - The objective of this study was to investigate the changes in soil microbial biomass C, microbial metabolic activity, functional diversity, and metabolic diversity pattern during the restoration process of a pine (Pinus tabulaeformis) plantation. In this study, a chronosequence approach was adopted. Three sites of pine plantations along a restoration chronosequence (12 years old (PF12), 25 years old (PF25), 35 years old (PF35)), and their paired reference sites of natural shrub community (Shrub1, Shrub2, and Shrub3) were selected. Soil microbial biomass C increased and microbial quotient declined with pine plantation age. Microbial metabolic activity, as measured by average well color development (using Biolog GN(2) plates), exhibited a decline along the restoration chronosequence with values ranked as PF12 > PF35 > PF25 in topsoil and PF12 > PF25 > PF35 in subsoil. Functional diversity, as estimated by substrate diversity and substrate richness, exhibited a pattern similar to the metabolic activity. Principal component analysis indicated that metabolic diversity followed recognized patterns along the restoration chronosequence with PF12 significantly different from PF25 and PF35. There was an apparent reduction of microbial metabolic activity and functional diversity during pine plantation restoration, which can be explained by a general decline in soil nutrient availability, particularly C availability, and soil pH associated with the establishment of a coniferous species. PMID- 20586777 TI - The adoption of conservation tillage in China. AB - Conservation tillage (CT) has been recognized as an advanced agricultural technology that may reduce drought and improve the physical condition of soils worldwide. An increase in water infiltration and a reduction in water and wind erosion can be achieved through the use of no-tillage, minimum tillage, and residue cover. In China, CT research started with support from the Ministry of Agriculture (MOA), China and the Australian Centre for International Agricultural Research in 1992. By the end of 1990s, CT research had expanded across China and achieved several important results. In 1999, MOA established the Conservation Tillage Research Centre (CTRC) to lead the national CT research programs in China, and since 2002 some CT demonstration projects have been established in northern China. By the end of 2008, CT has been demonstrated in 226 national and 365 provincial demonstration counties, covering more than 3 Mha. The CTRC of the MOA has established 10 sites within those counties to monitor project results. Some sites have shown consistently that the use of CT resulted in higher yields and net incomes, reduced soil erosion, and improved soil conditions. CT has been widely accepted in China and will be further adopted over wider areas as the development and highbred of indigenous no-tillage seeders. PMID- 20586778 TI - Successful treatment of disseminated granuloma annulare with methotrexate. PMID- 20586779 TI - Pemphigoid without mucosal involvement showing autoantibodies against laminin-332 gamma2 subunit. PMID- 20586781 TI - Bone regeneration using a hollow hydroxyapatite space-maintaining device for maxillary sinus floor augmentation--a clinical pilot study. AB - BACKGROUND: The mere lifting of the maxillary sinus membrane by implants protruding into the sinus cavity allows the establishment of a void space for blood clot and new bone formation. PURPOSE: To evaluate bone formation by using a spherical, hollow, and perforated hydroxyapatite space-maintaining device (HSMD) in a two-stage sinus lift procedure where residual alveolar bone height was <=2 mm. MATERIAL AND METHODS: Spherical, hollow, and perforated HSMDs with a diameter of 12 mm were manufactured for this pilot study. Three patients with a residual bone height of 1-2 mm, as verified clinically and radiographically, and in need of a sinus augmentation procedure prior to implant installation were selected for the study. The HSMD and bone formation was evaluated by cone beam computerized tomography (CBCT) 6 months after augmentation procedure. Implants were installed 6 to 9 months after augmentation. The implant sites were prepared by a trephine drill to obtain a specimen of HSMD and bone for histological evaluation. After implant installation, the condition of the sinus membrane adjacent to the HSMD was evaluated endoscopically. After an additional 8 weeks, fixed partial prostheses were fabricated. RESULTS: Bone formation verified by CBCT was found around and inside the device in all three patients after 6 months. Despite the fact that residual bone before augmentation was <=2 mm, 12-mm-long implants with diameter of 4.8 mm could be inserted with preservation of an intact and healthy sinus membrane verified endoscopically. Bone formation inside HSMDs was noted histologically in two out of three HSMDs. Implants were stable and without any marginal bone loss after 1 year of prosthetic loading. CONCLUSION: A spherical, hollow, and perforated HSMD used in sinus lift procedures can produce a void space for blood clot and new bone formation and subsequent implant installation. PMID- 20586780 TI - Matrix metalloproteinase-7 activates heparin-binding epidermal growth factor-like growth factor in cutaneous squamous cell carcinoma. AB - BACKGROUND: Tumour-specific expression of matrix metalloproteinase (MMP)-7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: To examine the potential role of MMP-7 in shedding of heparin-binding epidermal growth factor like growth factor (HB-EGF) in RDEB-associated and sporadic SCCs. METHODS: Tissue microarrays of RDEB-associated SCC (n = 20), non-EB SCC (n = 60) and Bowen disease (n = 28) were immunostained for MMP-7, CD44 variant 3 (CD44v3) and HB EGF. Shedding of HB-EGF was studied in vitro using two cutaneous SCC cell lines. RESULTS: Immunohistochemical analysis showed that HB-EGF was absent in tumour cells when MMP-7 and CD44v3 colocalized, and that the absence of HB-EGF was more pronounced in RDEB-associated SCCs than in non-EB SCCs. The loss of HB-EGF in MMP 7-CD44v3 double-positive areas was interpreted to indicate shedding and activation of HB-EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP-7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB-EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells. CONCLUSIONS: These findings provide evidence for the role of MMP-7 in promoting the growth of cutaneous SCCs by shedding HB-EGF, and identify EGFR signalling as a potential therapeutic target in RDEB-associated SCC and unresectable sporadic cutaneous SCC. PMID- 20586782 TI - Evaluation of the effectiveness of a water lift system in the sinus membrane lifting operation as a sinus surgical instrument. AB - PURPOSE: The effectiveness of a Water Lift System in the sinus membrane-lifting operation was examined. This investigation focused on the capability of this equipment to reduce the risk of Schneiderian membrane perforation. MATERIALS AND METHODS: A preliminary clinical study on the use of the Water Lift System in sinus membrane elevation to place implants through the sinus floor was conducted. A total of 70 sinus membrane-lifting operations were performed on patients with various bone heights ranging from 1.2 to 9.9 mm (most commonly in the range of 4 6 mm) through the lateral approach (four cases) or the crestal approach (66 cases). RESULTS: In all of the cases performed using the lateral approach, sinus membrane perforation did not occur. In the 66 cases performed using the crestal approach, Schneiderian membrane tearing occurred in two cases. The membrane tearing occurred during elevation of the Schneiderian membrane but not when a hole was drilled to access the Schneiderian membrane. One case of membrane tearing resulted from previous inflammation in the maxillary sinus, and the other case of membrane tearing was caused by application of excessive hydraulic pressure. In addition, similar outcomes were obtained and no microbial infections were observed in a total of 68 successful cases. CONCLUSIONS: In this study, the Water Lift System was confirmed to effectively reduce the risk of Schneiderian membrane perforation during the sinus membrane-lifting operation. We conclude that the Water Lift System deserves to be considered as a sinus surgical instrument, which ensures safety in the sinus membrane-lifting operation. PMID- 20586783 TI - Short communication: use of a diagnostic software to predict bone density and implant stability in preoperative CTs. AB - BACKGROUND: Computerized tomographs (CTs) are commonly used for presurgical planning of dental implant placement. It is possible that implant stability can be predicted based on quantitative measurements of bone density at planned implants sites with the use of diagnostic software. PURPOSE: The aim was to evaluate if there is a correlation between bone density measurements in specific implant positions in preoperative CTs and insertion torque (IT) and implant stability measurements when placing the implants. MATERIALS AND METHODS: The study comprised of four patients in whom presurgical CTs had been used to plan implant treatment. A total of 26 implants (Neoss, Harrogate, UK) were placed in the totally edentulous maxilla (n=3) or mandible (n=1). IT was measured during implant insertion and the torque/time curves examined for mean IT (newton centimeters) over the total curve. The stability of implants was measured with resonance frequency analysis. The positions of the implants were extracted from a postoperative CT to the preoperative one. Bone density was measured with a dedicated software (3DiagnosysTM 3.0, 3Diemme, Cantu, Italy) in virtual hollow probes, indicating the bone volume within 1mm from each implant surface. The Spearman Rank correlation test was used to find possible correlations. RESULTS: Statistically significant correlations were found between mean bone density, mean IT, and implant stability measurements. CONCLUSIONS: This pilot study showed a correlation between bone density, as measured in Hounsfield units in preoperative CTs, and IT and implant stability measurements at the surgical placement of the implants. The findings support the idea that integration of bone density measurements in implant probes in preoperative CTs using treatment-planning software may be a useful feature to predict implant stability and to avoid failures. PMID- 20586784 TI - Long-term follow-up of CeraOneTM single-implant restorations: an 18-year follow up study based on a prospective patient cohort. AB - BACKGROUND: Knowledge on long-term clinical performance of more than 5 years on the single-implant CeraOneTM (Nobel Biocare AB, Gothenburg, Sweden) concept is limited. PURPOSE: The aim of this study is to report the long-term clinical performance of the first CeraOne single-implant restorations, installed 17 to 19 years ago. MATERIALS AND METHODS: The group comprised 57 patients provided with 65 CeraOne single-tooth restorations. Sixty-two all-ceramic and three metal ceramic crowns were cemented between 1989 and 1991. Patients were followed up clinically and with intraoral radiographs at placement, after 1, 5, and between 17 and 19 years after placement. RESULTS: Data were available for altogether 48 patients, followed up on an average time of 18 years. Excluding deceased patients (n=2) and failed implant patients (n=2), only five patients were lost to follow up (8.8%). Two implants failed, resulting in an 18-year implant cumulative success rate (CSR) of 96.8%, and altogether eight original single-crown restorations were replaced (CSR 83.8%). The most common reason for crown replacement was infra-position of the implant crown (n=3). Many of the remaining original crowns showed various signs of implant crown infraposition at the termination of the study. In general, the soft tissue at the restorations was assessed to be healthy and comparable with the gingiva at the adjacent natural teeth. Bone levels were on an average stable with only few patients exhibiting bone loss of more than 2mm during 18 years in function. CONCLUSION: This long term follow-up study of single-implant restorations shows encouraging results with few implant failures and minimal bone loss over an 18-year period. Original single-crown restorations were replaced more frequently, because of, for example, implant crown infraposition and veneer fractures. The CeraOne concept proved to be a highly predictable and safe prosthodontic treatment. PMID- 20586785 TI - Evaluation of a new titanium-zirconium dental implant: a biomechanical and histological comparative study in the mini pig. AB - BACKGROUND: Titanium zirconium alloy with 13-17% zirconium (TiZr1317) shows significantly better mechanical attributes than pure Ti with respect to elongation and fatigue strength. This material may be suitable for thin implants and implant components exposed to high mechanical constraints. PURPOSE: The aim of this study was to test the hypothesis that TiZr1317 and Ti implants show comparable osseointegration and stability. MATERIALS AND METHODS: The mandibular premolars (P1, P2, P3) and the first molar (M1) in 12 adult miniature pigs were extracted 3 months prior to the study. Six specially designed implants made from Ti (commercially pure, Grade 4) or TiZr1317 (Roxolid(r), Institut Straumann AG, Basel, Switzerland) with a hydrophilic sandblasted and acid-etched (SLActive, Institut Straumann AG, Basel, Switzerland) surface were placed in each mandible; three standard implants modified for evaluation of removal torque (RT) in one side and three bone-chamber implants for histologic observations in the contralateral side. RT tests were performed after 4 weeks when also the bone chamber implants and surrounding tissue were biopsied for histologic analyses in ground sections. RESULTS: The RT results indicated significantly higher stability (p=0.013) for TiZr1317 (230.9+/-22.4Ncm) than for Ti implants (204.7+/-24.0Ncm). The histology showed similar osteoconductive properties for both implant types. Histomorphometric measurements showed a statistically significant higher (p=0.023) bone area within the chamber for the TiZr1317 implants (45.5+/-13.2%) than did the Ti implants (40.2+/-15.2%). No difference was observed concerning the bone to implant contact between the groups with 72.3+/-20.5% for Ti and 70.2+/-17.3% for TiZr1317 implants. CONCLUSION: It is concluded that the TiZr1317 implant with a hydrophilic sandblasted and acid-etched surface showed similar or even stronger bone tissue responses than the Ti control implant. PMID- 20586786 TI - Using cost-effective targeting to enhance the efficiency of conservation investments in payments for ecosystem services. AB - Ecosystem services are being protected and restored worldwide through payments for ecosystem services in which participants are paid to alter their land management approaches to benefit the environment. The efficiency of such investments depends on the design of the payment scheme. Land features have been used to measure the environmental benefits of and amount of payment for land enrollment in payment for ecosystem services schemes. Household characteristics of program participants, however, may also be important in the targeting of land for enrollment. We used the characteristics of households participating in China's Grain-to-Green program, and features of enrolled land to examine the targeting of land enrollment in that program in Wolong Nature Reserve. We compared levels of environmental benefits that can be obtained through cost effective targeting of land enrollment for different types of benefits under different payment schemes. The efficiency of investments in a discriminative payment scheme (payments differ according to opportunity costs, i.e., landholders' costs of forgoing alternative uses of land) was substantially higher than in a flat payment scheme (same price paid to all participants). Both optimal targeting and suboptimal targeting of land enrollment for environmental benefits achieved substantially more environmental benefits than random selection of land for enrollment. Our results suggest that cost-effective targeting of land through the use of discriminative conservation payments can substantially improve the efficiency of investments in the Grain-to-Green program and other payment for ecosystem services programs. PMID- 20586787 TI - Defining historical baselines for conservation: ecological changes since European settlement on Vancouver Island, Canada. AB - Conservation and restoration goals are often defined by historical baseline conditions that occurred prior to a particular period of human disturbance, such as European settlement in North America. Nevertheless, if ecosystems were heavily influenced by native peoples prior to European settlement, conservation efforts may require active management rather than simple removal of or reductions in recent forms of disturbance. We used pre-European settlement land survey records (1859-1874) and contemporary vegetation surveys to assess changes over the past 150 years in tree species and habitat composition, forest density, and tree size structure on southern Vancouver Island and Saltspring Island, British Columbia, Canada. Several lines of evidence support the hypothesis that frequent historical burning by native peoples, and subsequent fire suppression, have played dominant roles in shaping this landscape. First, the relative frequency of fire-sensitive species (e.g., cedar [Thuja plicata]) has increased, whereas fire-tolerant species (e.g., Douglas-fir [Pseudotsuga menziesii]) have decreased. Tree density has increased 2-fold, and the proportion of the landscape in forest has greatly increased at the expense of open habitats (plains, savannas), which today contain most of the region's threatened species. Finally, the frequency distribution of tree size has shifted from unimodal to monotonically decreasing, which suggests removal of an important barrier to tree recruitment. In addition, although most of the open habitats are associated with Garry oak (Quercus garryana) at present, most of the open habitats prior to European settlement were associated with Douglas-fir, which suggests that the current focus on Garry oak as a flagship for the many rare species in savannas may be misguided. Overall, our results indicate that the maintenance and restoration of open habitats will require active management and that historical records can provide critical guidance to such efforts. PMID- 20586788 TI - Inbreeding depression accumulation across life-history stages of the endangered Takahe. AB - Studies evaluating the impact of inbreeding depression on population viability of threatened species tend to focus on the effects of inbreeding at a single life history stage (e.g., juvenile survival). We examined the effects of inbreeding across the full life-history continuum, from survival up to adulthood, to subsequent reproductive success, and to the recruitment of second-generation offspring, in wild Takahe ( Porphyrio hochstetteri ) by analyzing pedigree and fitness data collected over 21 breeding seasons. Although the effect size of inbreeding at individual life-history stages was small, inbreeding depression accumulated across multiple life-history stages and ultimately reduced long-term fitness (i.e., successful recruitment of second-generation offspring). The estimated total lethal equivalents (2B) summed across all life-history stages were substantial (16.05, 95% CI 0.08-90.8) and equivalent to an 88% reduction in recruitment of second-generation offspring for closely related pairs (e.g., sib sib pairings) relative to unrelated pairs (according to the pedigree). A history of small population size in the Takahe could have contributed to partial purging of the genetic load and the low level of inbreeding depression detected at each single life-history stage. Nevertheless, our results indicate that such "purged" populations can still exhibit substantial inbreeding depression, especially when small but negative fitness effects accumulate across the species' life history. Because inbreeding depression can ultimately affect population viability of small, isolated populations, our results illustrate the importance of measuring the effects of inbreeding across the full life-history continuum. PMID- 20586789 TI - Some guiding concepts for conservation biology. AB - The search for generalities in ecology has often been thwarted by contingency and ecological complexity that limit the development of predictive rules. We present a set of concepts that we believe succinctly expresses some of the fundamental ideas in conservation biology. (1) Successful conservation management requires explicit goals and objectives. (2) The overall goal of biodiversity management will usually be to maintain or restore biodiversity, not to maximize species richness. (3) A holistic approach is needed to solve conservation problems. (4) Diverse approaches to management can provide diverse environmental conditions and mitigate risk. (5) Using nature's template is important for guiding conservation management, but it is not a panacea. (6) Focusing on causes not symptoms enhances efficacy and efficiency of conservation actions. (7) Every species and ecosystem is unique, to some degree. (8) Threshold responses are important but not ubiquitous. (9) Multiple stressors often exert critical effects on species and ecosystems. (10) Human values are variable and dynamic and significantly shape conservation efforts. We believe most conservation biologists will broadly agree these concepts are important. That said, an important part of the maturation of conservation biology as a discipline is constructive debate about additional or alternative concepts to those we have proposed here. Therefore, we have established a web-based, online process for further discussion of the concepts outlined in this paper and developing additional ones. PMID- 20586790 TI - Recent insights into pre- and postnatal pyridoxal phosphate deficiency, a treatable metabolic encephalopathy. PMID- 20586791 TI - Rapid assessment of postural instability in Parkinson's disease (RAPID): a pilot study. AB - BACKGROUND: The Fahn's pull (or retropulsion) test is an item in the motor section of the Unified Parkinson's Disease Rating Scale, which is used almost exclusively to classify postural instability in Parkinson's disease (PD). However, the test is hard to standardize and is often performed incorrectly, making it hard to interpret. Moreover, it may not be safe to administer in patients who experience pain in the shoulders, neck, trunk and/or lower extremities. Identifying and grading postural instability in PD without requiring a physical challenge would not only be useful for the clinician but would assist patients and caregivers in its recognition. We propose the use of the rapid assessment of postural instability in Parkinson's disease (RAPID) questionnaire as a non-physical assessment tool. METHODS: We determined the associations between the pull test and items on a risk-assessment questionnaire that consisted of three parts: activities of daily living, fear of falling, and frequency of falling. RESULTS: Significant correlations were found between the pull test and the predictor variables, which ranged between 0.51 and 0.56 whilst the correlations amongst the predictor variables ranged between 0.58 and 0.70. The three parts of the questionnaire, when used in combination, produced a 96% sensitivity in the classification of postural instability. CONCLUSIONS: The RAPID questionnaire can be used as an adjunct to the pull test or solely if the pull test is contraindicated. It may also be possible to administer the questionnaire via the telephone or Internet. It is hoped that the rapid identification of postural instability would lead to fewer falls. PMID- 20586792 TI - HFE gene polymorphisms and severity in Portuguese patients with multiple sclerosis. AB - BACKGROUND: High iron concentrations have been reported in oligodendrocytes, myelin and macrophages in multiple sclerosis (MS) lesions. It has been proposed that HFE gene polymorphisms could have a role in MS. METHODS: The C282Y and H63D HFE variants frequencies were determined in 373 patients with MS and compared with a normal population. RESULTS: No significant association was found between HFE polymorphisms and disease susceptibility. An analysis of the association of genotypes with disease severity was performed, and the C282Y allele was more frequent in the aggressive group. CONCLUSIONS: Patients carrying the C282Y variant seem to have a worse prognosis. PMID- 20586793 TI - 10th Novo Nordisk Symposium on Haemostasis Management--introduction. PMID- 20586794 TI - 10th anniversary of the haemophilia/haemostasis Novo Nordisk symposium. PMID- 20586795 TI - Plasma and cellular contributions to fibrin network formation, structure and stability. AB - Growing evidence suggests that fibrin network structure and stability are important determinants of haemostasis and thrombosis, with alterations in fibrin structure implicated as a causative mechanism in various haemostatic and thrombotic disorders. In haemophilia, for example, deficiency of factor VIII or IX reduces the rate and peak of thrombin generation and produces coarse fibrin clots that show increased susceptibility to fibrinolysis. More recently, studies have shown significant effects of cellular activity and integrin composition on fibrin network and stability. Platelets support the formation of a dense, stable fibrin network via interactions between the alphaIIbbeta3 integrin and the fibrin network, whereas tissue factor-bearing cells regulate fibrin structure and stability predominantly via procoagulant activity. Highly procoagulant extravascular cells (e.g. fibroblasts and smooth muscle cells) support the formation of dense fibrin networks that resist fibrinolysis, whereas unstimulated intravascular cells (e.g. endothelial cells) produce coarser networks that are susceptible to fibrinolysis. Moreover, cellular contributions produce heterogeneous clots in which fibrin network density and stability decrease with increasing distance from the cell surface. Together, these findings suggest that specific plasma and cellular mechanisms link thrombin generation, clot stability and haemostatic or thrombotic outcome. Understanding these mechanisms may provide new therapeutic targets in the management of bleeding and thrombotic disorders. PMID- 20586796 TI - Wound healing in haemophilia--breaking the vicious cycle. AB - Our group has been studying how haemostasis interacts with repair processes and also how to optimize treatment of bleeding disorders in a mouse model of haemophilia B. We have found that cutaneous wounds heal more slowly in haemophilic mice than in wild-type mice, and also exhibit histological abnormalities, even after closure of the skin defect. The haemophilic wounds showed reduced influx of inflammatory cells and increased angiogenesis. Even after surface closure, the haemophilic animals experienced repeated episodes of re-bleeding and progressive accumulation of iron in the wound bed and deeper tissues. A dose of replacement or bypassing therapy sufficient to establish initial haemostasis did not normalize wound healing. In fact, daily dosing for 7 days was required to normalize wound closure. Thus, normal healing requires adequate haemostatic function for an extended period of time. We have hypothesized that this is because angiogenesis during healing predisposes to bleeding, especially in the setting where haemostasis is impaired. Thus, normalizing haemostasis, until the process of angiogenesis has resolved, may be required to prevent re-bleeding and additional tissue damage. PMID- 20586797 TI - Prevention of spontaneous bleeding in dogs with haemophilia A and haemophilia B. AB - Dogs with haemophilia A or haemophilia B exhibit spontaneous bleeding comparable with the spontaneous bleeding phenotype that occurs in humans with severe haemophilia. The phenotypic and genotypic characteristics of haemophilic dogs have been well-described, and such dogs are suitable for testing prophylactic protein replacement therapy and gene transfer strategies. In dogs with haemophilia, long-term effects on spontaneous bleeding frequency (measured over years) can be used as an efficacy endpoint in such studies. Although complete correction of coagulopathy has not been achieved, published data show that prophylactic factor replacement therapy and gene transfer can markedly reduce the frequency of spontaneous bleeding in haemophilic dogs. Further studies are currently ongoing. PMID- 20586798 TI - Gene therapy in haemophilia--going for cure? AB - Traditional treatment for haemophilia consists of bolus infusion of the missing coagulation factor, either prophylactically or on demand, but is complicated by the development of inhibitory antibodies to the infused factor. In those cases, as well as in patients with platelet defects or factor VII (FVII) deficiency, recombinant human activated FVII has been successfully used, but carries the disadvantage of a short plasma half-life. As an alternative, emerging methodology based on gene transfer may be utilized to provide effective haemostasis in patients with coagulation defects. The goal of this article is to introduce the novel concept of continuous expression of activated FVII from a donated gene for the treatment of haemophilia, and to review the safety and efficacy data that have been produced so far by this approach in small and large animal models. PMID- 20586799 TI - Health economics in haemophilia: a review from the clinician's perspective. AB - Health economic evaluations provide valuable information for healthcare providers, facilitating the treatment decision-making process in a climate where demand for healthcare exceeds the supply. Although an uncommon disease, haemophilia is a life-long condition that places a considerable burden on patients, healthcare systems and society. This burden is particularly large for patients with haemophilia with inhibitors, who can develop serious bleeding complications unresponsive to standard factor replacement therapies. Hence, bleeding episodes in these patients are treated with bypassing agents such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrates (pd-APCC). With the efficacy of these agents now well established, a number of health economic studies have been conducted to compare their cost-effectiveness for the on-demand treatment of bleeding episodes in haemophiliacs with inhibitors. In a cost-utility analysis, which assesses the effects of treatment on quality of life (QoL) and quantity of life, the incremental cost per quality-adjusted life-year (QALY) gained (US $44,834) indicated that rFVIIa was cost-effective. Similarly, eight of 11 other economic modelling evaluations found that rFVIIa was more cost-effective than pd-APCC in the on-demand treatment of bleeding episodes. These findings indicate that treating patients with haemophilia promptly and with the most effective therapy available may result in cost savings. PMID- 20586800 TI - Optimizing on-demand treatment with NovoSeven room temperature stable. AB - Patients with haemophilia can now look forward to greater life expectancy than ever before--a development that can be attributed to improved healthcare strategies and more effective treatments. In the last few decades, the treatment of haemophilia patients with inhibitors has also witnessed dramatic improvements through the development of bypassing agents, including recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk, Bagsvaerd, Denmark). Growing evidence suggests that early initiation of treatment with rFVIIa results in greater haemostatic efficacy with fewer doses, leading to improved overall outcome. The new NovoSeven room temperature stable formulation has been designed to optimize on-demand treatment by facilitating early initiation of therapy for haemorrhagic episodes, which brings the potential benefits of faster bleed resolution, reduced frequency of re-bleeding and reduced product consumption. This is particularly important for inhibitor patients, in whom orthopaedic complications are more severe than in non-inhibitor patients. Early treatment might help improve musculoskeletal status and therefore reduce disability, which improves patient quality of life and aids integration into society. These clinical advantages are also accompanied by both short-term and long-term economic benefits. NovoSeven room temperature stable might also improve patient compliance and treatment convenience, as patients can carry their treatment with them and administer it wherever they are, without being restricted by the need for a refrigerator and without the need to visit a hospital or to return home. The potential benefits of NovoSeven room temperature stable make this new formulation a valuable addition to our armamentarium in the ongoing effort to improve haemophilia care. PMID- 20586801 TI - Genetic markers in acquired haemophilia. AB - Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4) play an important role in the maintenance of peripheral T-cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA-4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA-4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17). This observation was mainly because of a higher frequency of the CTLA-4 + 49 G allele in female patients. These findings suggest that immune response genes may contribute to the development of anti-factor VIII autoantibodies in AH. PMID- 20586802 TI - Meeting unmet needs in inhibitor patients. AB - For patients with haemophilia, the development of inhibitors complicates treatment, and inhibitor patients may thus have a range of unmet needs. Although successful inhibitor eradication will render patients responsive to factor replacement therapy, with potentially beneficial effects on long-term outcomes, this may not always be possible. Physicians treating inhibitor patients should aim to achieve reliable control of bleeding episodes, and the prevention of joint disease should also be a priority. Patients with high-titre inhibitors require therapy with bypassing agents--recombinant activated factor VII (rFVIIa) or a plasma-derived activated prothrombin complex concentrate (pd-APCC)--for the treatment of bleeding. When treating joint haemorrhage in inhibitor patients, both aggressive treatment of intercurrent joint bleeds and prophylaxis should be considered, although evidence is needed as to whether prophylaxis with bypassing agents can significantly delay/prevent the development of osteochondral changes in patients with inhibitors. Despite physicians' best efforts, joint disease may ultimately occur in inhibitor patients, and in such instances optimizing treatment, of both early and late stages, is important. There is no single therapeutic modality for dealing with the various treatment challenges posed by inhibitor patients, but overall goals should be to improve quality of life, with the provision of cost-effective care that aims to maintain physical function. PMID- 20586803 TI - Management of difficult-to-treat inhibitor patients. AB - The workshop looked at seven scenarios based on fictional and real-life cases of difficult-to-treat patients with haemophilia A or haemophilia B and inhibitors with the aim of sharing clinical opinion and experience from around the world. Delegate opinions on the best treatment option for each scenario are described together with actual treatment given in real-life cases and its outcome. PMID- 20586804 TI - Cardiovascular disease in haemophilia patients: a contemporary issue. AB - Improvements in treatment options and healthcare provision mean that haemophilia patients now have a life expectancy approaching that of the normal male population. An increased life expectancy, however, also brings an increased risk of developing age-related disorders, the foremost of which is cardiovascular disease. The epitome of age-related morbidity, cardiovascular disease is also a leading cause of mortality in elderly individuals, and presents a particular challenge when it occurs in persons with haemophilia. While the exact incidence of cardiovascular disease in haemophilia is unknown, incidence rates from conditions such as ischaemic heart disease (IHD) have steadily risen over the last 20-30 years, suggesting that cardiac problems are increasingly relevant for these patients. Management of cardiovascular disease in haemophilia warrants close cooperation between cardiologists and haematologists, and evidence-based guidelines are not available. In the absence of such guidelines, antithrombotic treatment is currently based on local clinical experience and adaptation of the general guidelines used in the non-haemophilic population. In this article, we outline the local guidelines used by our two centres in the antithrombotic treatment of IHD, coronary bypass and valve surgery, and atrial fibrillation in patients with haemophilia. Strategies for the management of haemostasis and thrombosis during cardiovascular surgery in haemophilia patients are also briefly reviewed. Finally, we present the cases of three elderly haemophilia patients with cardiovascular and other age-related health problems in whom such treatment strategies were applied. PMID- 20586808 TI - Clinical Practice Guidelines for Hepatocellular Carcinoma - The Japan Society of Hepatology 2009 update. PMID- 20586807 TI - Abstracts of the 52nd Annual Scientific Meeting of the American Headache Society. June 24-27, 2010. Los Angeles, California, USA. PMID- 20586809 TI - Abstracts of the Second Joint Conference of the British HIV Association and the British Association for Sexual Health and HIV. April 20-23, 2010. Manchester, United Kingdom. PMID- 20586812 TI - Abstracts of ISIRV International Symposium on Viral Respiratory Disease Surveillance. Seville, Spain. March 25-27, 2009. PMID- 20586810 TI - Autophagy and adaptive immunity. AB - Autophagy plays an important role in maintaining intracellular homeostasis by promoting the transit of cytoplasmic material, such as proteins, organelles and pathogens, for degradation within acidic organelles. Yet, in immune cells, autophagy pathways serve an additional role in facilitating intracellular surveillance for pathogens and changes in self. Autophagy pathways can modulate key steps in the development of innate and adaptive immunity. In terms of adaptive immunity, autophagy regulates the development and survival of lymphocytes as well as the modulation of antigen processing and presentation. Specialized forms of autophagy may be induced by some viral pathogens, providing a novel route for major histocompatibility complex (MHC) class I antigen presentation and enhanced CD8(+) T-cell responses. Autophagy induction in target cells also increases their potential to serve as immunogens for dendritic cell cross-presentation to CD8(+) T cells. The requirement for autophagy in MHC class II presentation of cytoplasmic and nuclear antigens is well established, yet recent studies also point to a critical role for autophagy in modulating CD4(+) T cell responses to phagocytosed pathogens. Autophagy pathways can also modulate the selection and survival of some CD4(+) T cells in the thymus. However, much still remains to be learned mechanistically with respect to how autophagy and autophagy-linked genes regulate pathogen recognition and antigen presentation, as well as the development and survival of immune cells. PMID- 20586811 TI - Detection of mumps virus-specific memory B cells by transfer of peripheral blood mononuclear cells into immune-deficient mice. AB - Waning immunity to mumps after one or two doses of the measles, mumps and rubella (MMR) vaccine has been described. Using a human peripheral blood lymphocyte (PBL) severe combined immunodeficiency (SCID) mouse model, MMR vaccine recipients with undetectable and high antibody titres against mumps were compared for the presence of circulating mumps-specific memory B cells. Peripheral blood mononuclear cells (PBMC) from six donors (three subjects with undetectable and three with high antibody titres against mumps) were injected into the spleens of non-obese diabetic (NOD)-SCID mice (three mice per subject). Mice were pretreated with TMbeta1 and total body irradiation to improve engraftment. In vivo production of human antibodies against mumps was evaluated in mouse plasma on days 7, 10 and 13 with a commercial enzyme-linked immunosorbent assay (ELISA), functional reduction neutralization test. Three donors had mumps antibody titres below the detection limit (titre < 230) and three had high antibody titres (range 5700-7300). None of the mice injected with PBMC from subjects with undetectable antibody titres showed detectable human antibody titres, despite the presence of cell-mediated immunity in two of the three donors. Seven out of nine mice injected with PBMC from subjects with high antibody titres acquired detectable antibody titres for mumps in their plasma. PBMC from vaccinees without detectable serum antibodies against mumps virus were unable to induce secretion of anti mumps antibodies in the blood of recipient mice, whereas PBMC from vaccinees with high antibody titres were able to do so. This observation suggests that the frequency of mumps-specific memory B cells is very low in vaccinees with undetectable antibody titres. These individuals may therefore be at risk of developing mumps disease upon encounter with wild-type virus. PMID- 20586813 TI - Adenohypophysitis in rat pituitary allografts. AB - The histological, immunohistochemical and ultrastructural alterations in 81 pituitary allografts from Lewis rats transplanted beneath the renal capsule of Wistar rats were investigated. Intrasellar pituitaries of rats bearing allografts were also examined. Recipient rats were sacrificed at various time points after transplantation. Two days after transplantation, the central portion of the allografts demonstrated ischaemic necrosis. A week later, massive mononuclear cell infiltrates consisting primarily of lymphocytes and to a lesser extent, macrophages, plasma cells and granulocytes became prominent. At about three to four weeks after transplantation, the mononuclear cell infiltrate diminished; the surviving adenohypophysial cells, mainly prolactin (PRL) cells, increased in number and necrosis was replaced by connective tissue. No histological changes were noted in the intrasellar pituitaries of rats bearing allografts. Immunohistochemistry demonstrated that the surviving adenohypophysial cells were mainly PRL-producing cells. Electron microscopy revealed adenohypophysial cell destruction, a spectrum of inflammatory cells and, in late phase, accumulation of fibroblasts and collagen fibres. PRL cells were the prominent cell types; they increased in number. It appears that pituitary allografts are 'foreign' and evoke an immune response, suggesting that they may be used as an experimental animal model for morphological investigation of the development and progression of adenohypophysitis, a rare disease occurring mainly in young women often associated with pregnancy. PMID- 20586814 TI - Establishment and characterization of a murine xenograft model of appendiceal mucinous adenocarcinoma. AB - We describe the clinical, pathologic and molecular characteristics of a xenograft model of metastatic mucinous appendiceal adenocarcinoma. Tumours from patients with mucinous appendiceal neoplasms were implanted in nude mice and observed for evidence of intraperitoneal tumour growth. Morphologic and immunohistochemical features, temporal growth characteristics relative to controls, and loss of heterozygosity (LOH) at multiple chromosomal alleles were assessed in a successfully engrafted tumour. Two of seventeen implanted tumours successfully engrafted and only one mucinous adenocarcinoma propagated throughout the course of the study. The successful xenograft is morphologically similar to the original tumour, produces abundant extracellular mucin and exhibits non-invasive growth on peritoneal surfaces. The temporal growth characteristics of the xenograft tumour relative to controls reveal that tumour burden can be followed indirectly by measuring the weight or abdominal girth of engrafted animals. The cytokeratin, mucin core protein, CDX2, Ki-67 and p53 expression patterns are identical in the xenograft and resected tumour and are consistent with the expected pattern of protein expression for mucinous adenocarcinoma of the appendix. LOH was found in 1 of 10 informative chromosomal loci (chromosome 10p23) in xenograft tumour cells. Although we were unable to engraft a low-grade appendiceal mucinous neoplasm, the engrafted adenocarcinoma will be useful for future evaluation of novel therapeutic strategies directed at mucinous appendiceal adenocarcinoma and evaluation of strategies for treating widespread, bulky, mucinous peritoneal surface neoplasms. Xenograft tumour enrichment can facilitate molecular studies of appendiceal epithelial neoplasia. PMID- 20586816 TI - Effects of long-term diabetes on the structure and cell proliferation of the myometrium in the early pregnancy of mice. AB - It is known that the development of diabetic complications in human pregnancy is directly related to the severity and the duration of this pathology. In this study, we developed a model of long-term type 1 diabetes to investigate its effects on the cytoarchitecture, extracellular matrix and cell proliferation during the first adaptation phase of the myometrium for pregnancy. A single dose of alloxan was used to induce diabetes in mice prior to pregnancy. To identify the temporal effects of diabetes the mice were divided into two groups: Group D1 (females that became pregnant 90-100 days after alloxan); Group D2 (females that became pregnant 100-110 days after alloxan). Uterine samples were collected after 168 h of pregnancy and processed for light and electron microscopy. In both groups the histomorphometric evaluation showed that diabetes promoted narrowing of the myometrial muscle layers which was correlated with decreased cell proliferation demonstrated by PCNA immunodetection. In D1, diabetes increased the distance between muscle layers and promoted oedema. Contrarily, in D2 the distance between muscle layers decreased and, instead of oedema, there was a markedly deposition of collagen in the myometrium. Ultrastructural analysis showed that diabetes affects the organization of the smooth muscle cells and their myofilaments. Consistently, the immunoreaction for smooth muscle alpha actin revealed clear disorganization of the contractile apparatus in both diabetic groups. In conclusion, the present model demonstrated that long-term diabetes promotes significant alterations in the myometrium in a time-sensitive manner. Together, these alterations indicate that diabetes impairs the first phenotypic adaptation phase of the pregnant myometrium. PMID- 20586815 TI - SDF-1alpha/CXCR4 axis is involved in glucose-potentiated proliferation and chemotaxis in rat vascular smooth muscle cells. AB - Excessive proliferation of vascular smooth muscle cells (VSMCs), which migrate from the tunica media to the subendothelial region, is one of the primary lesions involved in atherogenesis in diabetes. Here, we investigated whether high glucose potentiated the proliferation and chemotaxis of VSMCs by activating SDF 1alpha/CXCR4/PI-3K/Akt signalling. The expression of SDF-1alpha, CXCR4 and PCNA was up-regulated in tunica media of thoracic aortas by streptozotocin-induced hyperglycaemic Sprague-Dawley rats. Exposure of primary VSMCs to high glucose (25 mM) led to the up-regulated expression of SDF-1alpha and CXCR4, activated PI 3K/Akt signalling, and consequently promoted the proliferation and chemotaxis of VSMCs. Interestingly, the administration of SDF-1 siRNA or neutralizing antibody against SDF-1alpha abolished high glucose-induced up-regulation of CXCR4. Moreover, pretreatment with SDF-1alpha neutralizing antibody, CXCR4 specific inhibitor (AMD3100) or PI-3K inhibitor (LY294002) attenuated the high glucose potentiated proliferation and chemotaxis in VSMCs. These results suggested that high glucose activated the SDF-1alpha/CXCR4/PI-3K/Akt signalling pathway in VSMCs in an autocrine manner, which enhanced the proliferation and chemotaxis of VSMCs. PMID- 20586817 TI - Histopathological analysis of initial cellular response in TLR-2 deficient mice experimentally infected by Leishmania (L.) amazonensis. AB - Tegumentary leishmaniasis is an important public health problem in several countries. The capacity of the Leishmania species, at the initial moments of the infection, to invade and survive inside the host cells involves the interaction of surface molecules that are crucial in determining the evolution of the disease. Using C57BL/6 wild-type and TLR-2(-/-) mice infected with L. (L.) amazonensis, we demonstrated that TLR-2(-/-) mice presented eosinophilic granuloma in the ear dermis, different from C57BL/6 wild-type mice that presented a cellular profile characterized mainly by mononuclear cell infiltrates, besides neutrophils and eosinophils, during the two first week of infection. When the parasite load was evaluated, we found that the absence of TLR-2 lead to a significant reduction of the infection in deficient mice, when compared with C57BL/6 mice which were more susceptible to the infection. Using TLR-2 deficient mice, it was possible to show that the absence of this receptor determined the reduction of the parasite load and the recruitment of inflammatory cells during the two first weeks after L. (L.) amazonensis infection. PMID- 20586818 TI - Thyrocyte interleukin-18 expression is up-regulated by interferon-gamma and may contribute to thyroid destruction in Hashimoto's thyroiditis. AB - Interferon-gamma (IFN-gamma) has a direct role in thyroid destruction in autoimmune thyroiditis. Interleukin-18 (IL-18), a pro-inflammatory cytokine with potent IFN-gamma inducing activities, may play an important role in Th1-mediated autoimmune diseases. The purpose of this study was to characterize the expression and localization of IL-18 in the thyroid tissues of Hashimoto's thyroiditis (HT) and to investigate the effect of IFN-gamma on IL-18 expression in isolated human thyroid follicular cells (TFCs). Thyroid tissues obtained from six euthyroid patients with HT and six control subjects were used to detect IL-18 expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining. Human TFCs were isolated and incubated for 48 h with or without IFN gamma, tumour necrosis factor-alpha (TNF-alpha) or IL-1beta. IL-18 expression was analysed by RT-PCR, immunofluorescent double staining and western blot. We found that IL-18 expression was increased in the thyroid tissues of HT compared with control thyroid tissues. TFCs were major cell types expressing IL-18 in the thyroid tissues of HT. IL-18 was constitutively expressed in isolated human TFCs, and the expression was significantly up-regulated by IFN-gamma rather than TNF alpha or IL-1beta. Western bolt revealed that a 24-kDa band corresponding to pro IL-18 was broadened in the lysates of IFN-gamma-treated TFCs. Our results demonstrated that IL-18 expression is up-regulated in the TFCs of HT patients and in primary human TFCs exposed to IFN-gamma. Therefore, intrathyroidal interaction between IL-18 and IFN-gamma may have a role in promoting the local immune response, which contributes to the thyroid destruction seen in HT. PMID- 20586819 TI - Characteristics and clinical outcomes of renal cell carcinoma in children: a single center experience. AB - The present study aimed to assess the clinicopathological characteristics and the prognosis of renal cell carcinoma (RCC) in children. We retrospectively reviewed the medical records of 11 Korean children (7 boys and 4 girls) undergoing radical nephrectomy for RCC between September 1997 and January 2008 at our institution. Mean age at diagnosis was 12.7 years. The presenting clinical signs and symptoms included gross hematuria (55%), abdominal mass (45%) and abdominal pain (45%). Two (18%) of the cases were discovered incidentally. Five (45%) were conventional clear cell, four (36%) were papillary, one was a chromophobe and one was a translocation carcinoma. Seven children were T1N0M0, three were T2N0M0 and one child was T1N1M0. While one patient with T2 disease died of disease 89 months postoperatively, the remaining 10 patients, including a patient with regional nodal disease who received adjuvant immunochemotherapy, survived without evidence of recurrence at a mean follow-up of 6.8 years. Our data suggest that the clinical presentation, pathological characteristics and clinical behavior of pediatric RCC are different from those of adult RCC. PMID- 20586820 TI - Symmetrical peripheral digital gangrene following severe Plasmodium falciparum malaria-induced disseminated intravascular coagulopathy. AB - Symmetrical peripheral digital gangrene is a life-changing complication, caused by a pro-thrombotic life-threatening disease, such as disseminated intravascular coagulopathy (DIC) secondary to systemic infection. We describe the unusual case of a woman who developed symmetrical peripheral digital gangrene following DIC because of malaria. While initial treatment led to cure of the infection, in this report we describe also the subsequent management of symmetrical peripheral digital gangrene. PMID- 20586821 TI - Abstracts of the American Geriatrics Society 2010 Annual Scientific Meeting. May 12-15, 2010. Orlando, Florida, USA. PMID- 20586822 TI - Seeing is believing: unmasking left atrial appendage activity recorded in the left superior pulmonary vein without stimulation. PMID- 20586823 TI - Ventricular fibrillation during AV reentrant tachycardia. PMID- 20586824 TI - Radiation induced soft tissue necrosis: an underestimated complication after cardiac catheter ablation. PMID- 20586825 TI - Syncope and structural heart disease: historical criteria for vasovagal syncope and ventricular tachycardia. AB - INTRODUCTION: to develop evidence-based criteria that distinguish syncope due to ventricular tachycardia (VT) from vasovagal syncope (VVS) in patients with structural heart disease (SHD). METHODS AND RESULTS: one hundred and thirty-four patients with syncope and SHD completed a 118-item questionnaire and underwent noninvasive and invasive diagnostic assessments in a prospective cohort study. The contributions of symptoms to diagnoses were estimated with logistic regression and a point score was developed and then tested using receiver operator characteristic analysis. The effectiveness of the decision rule was evaluated with long-term outcome. There were 21 patients with tilt-positive VVS, 78 with clinically declared or inducible VT, and 35 with no identified cause of syncope. Six features were significant predictors. Factors that predicted VT included male sex and age at onset >35 years; factors predicting VVS included prolonged sitting or standing; developing presyncope preceded by stress; recurrent headaches; and experiencing fatigue, which lasts longer than 1 minute after syncope. The point score correctly classified 92% of patients, diagnosing VT with 99% sensitivity and 68% specificity. The negative predictive value is >= 96%. Fully 67% of patients with undiagnosed syncope were classified as having VT based upon their symptoms. The decision rule predicted 9-year arrhythmia-free survival (VVS 84%, VT 39%, hazard ratio 4.32) and 9-year overall survival (VVS 66%, VT 37%, hazard ratio 2.87). CONCLUSIONS: the causes of syncope in patients with SHD, and their clinical outcomes, can be estimated accurately based on the clinical history. The history safely screens out the possibility of VT as a cause of syncope. PMID- 20586826 TI - The P-selectin gene polymorphism Val168Met: a novel risk marker for the occurrence of primary ventricular fibrillation during acute myocardial infarction. AB - The P-Selectin Gene Polymorphism Val168Met. AIMS: Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD). Family history of SCD is described as risk factor for primary VF during acute AMI. Genetic factors may be associated with primary VF. We examined polymorphisms in genes related to the activation and adhesion of blood platelets in patients with and without VF in the setting of AMI and among healthy controls. METHODS: Two hundred and forty patients with a history of AMI and 475 healthy controls were studied. Seventy-three patients (30%) had primary VF during AMI. By using PCR techniques with sequence-specific primers (PCR-SSP), we genotyped 5 single nucleotide polymorphisms (SNPs) in P-selectin (SELP) (V168M, S290N, N592D, V599L, T715P), 2 SNPs (M62I, S273F) in P-selectin glycoprotein ligand-1 (SELPLG), 5 SNPs in CD40LG (-3459A>G, -122A>C, -123A>C, 148T>C, intr4-13T>C), the H558R SNP in SCN5A, and rs2106261 in ZFHX3. In addition, length polymorphisms in SELPLG (36bp-tandem repeat) and CD40LG (CA repeat) were genotyped by PCR methods. Results were evaluated by 2-sided t-tests, chi-square tests, and logistic regression analysis. RESULTS: None of the gene polymorphisms showed significant differences between AMI patients and healthy controls. Among patients with a history of VF, however, the SELP 168M variant showed a significantly higher prevalence (14/73 patients; 19.2%) as compared with patients without VF (13/167 patients; 7.8%; P < 0.01). This association remained significant in a logistic regression analysis after adjustment for age and gender (P = 0.013; odds ratio 2.8; 95% confidence interval 1.2-6.3). CONCLUSIONS: This is the first description of an association of the SELP gene variant 168M with primary VF during acute MI. This variant may be a candidate polymorphism for evaluating the susceptibility for VF in the setting of acute MI. PMID- 20586827 TI - Incidence and electrophysiologic properties of dissociated pulmonary vein activity following pulmonary vein isolation during catheter ablation of atrial fibrillation. AB - INTRODUCTION: pulmonary veins (PV) play an important role in the arrhythmogenesis of atrial fibrillation (AF). Catheter-based PV isolation is one of the primary treatments for symptomatic drug refractory AF. Following electrical isolation, isolated rhythms in the PV are encountered. The aim of this study was to assess the frequency of postisolation PV activity and classify the different rhythms observed. METHODS AND RESULTS: this single center prospective study sought to assess the dissociated activity in the PVs following their isolation during AF ablation. In 100 consecutive patients (60 paroxysmal, 40 persistent) undergoing AF ablation, dissociated PV activity was recorded using a multielectrode mapping catheter following antral PV isolation. The dissociated PV activity was classified as (1) silent, (2) isolated ectopic beats, (3) ectopic rhythm, and (4) PV fibrillation. All the PVs were successfully isolated in all the patients. In 91 of 100 patients, there was dissociated activity in at least 1 isolated ipsilateral PV group. There was no significant difference in spontaneous PV activity between patients with paroxysmal and persistent AF (91.7% vs 90%, P = 1.0). Among the 200 isolated ipsilateral PV groups, 64 of 200 (32%) were silent, 86 of 200 (43%) demonstrated isolated ectopic beats, 41 of 200 (20.5%) had ectopic rhythms and 9 of 200 (4.5%) had PV fibrillation. The average cycle length of the PV ectopic rhythm was 2594 +/- 966 ms (range 1193-4750 ms). CONCLUSIONS: following PV isolation, a majority of patients demonstrate dissociated activity in at least 1 PV. This finding was evident in patients with both paroxysmal and persistent AF. PMID- 20586828 TI - Clinical significance of early recurrences of atrial tachycardia after atrial fibrillation ablation. AB - BACKGROUND: atrial tachycardia (AT) commonly recurs within 3 months after radiofrequency catheter ablation for atrial fibrillation (AF). However, it remains unclear whether early recurrence of atrial tachycardia (ERAT) predicts late recurrence of AF or AT. METHODS: of 352 consecutive patients who underwent circumferential pulmonary vein isolation with or without linear ablation(s) for AF, 56 patients (15.9%) with ERAT were identified by retrospective analysis. ERAT was defined as early relapse of AT within a 3-month blanking period after ablation. RESULTS: during 21.7 +/- 12.5 months, the rate of late recurrence was higher in patients with ERAT (41.1%) compared with those without ERAT (11.8%, P < 0.001). In a multivariable model, positive inducibility of AF or AT immediately after ablation (65.2% vs 36.4%, P = 0.046; odd ratio, 3.9; 95% confidence interval, 1.0-14.6) and the number of patients who underwent cavotricuspid isthmus (CTI) ablation (73.9% vs 42.4%, P = 0.042; odd ratio, 4.5; 95% confidence interval, 1.1-19.5) were significantly related to late recurrence in the ERAT group. The duration of ablation (174.3 +/- 62.3 vs 114.7 +/- 39.5 minutes, P = 0.046) and the procedure time (329.3 +/- 83.4 vs 279.2 +/- 79.7 minutes, P = 0.027) were significantly longer in patients with late recurrence than in those without late recurrence following ERAT. CONCLUSIONS: the late recurrence rate is higher in the patients with ERAT compared with those without ERAT following AF ablation, and is more often noted in the patients who underwent CTI ablation and had a prolonged procedure time. Furthermore, inducibility of AF or AT immediately after ablation independently predicts late recurrence in patients with ERAT. PMID- 20586829 TI - Generation of easily accessible human kidney tubules on two-dimensional surfaces in vitro. AB - The generation of tissue-like structures in vitro is of major interest for various fields of research including in vitro toxicology, regenerative therapies and tissue engineering. Usually 3D matrices are used to engineer tissue-like structures in vitro, and for the generation of kidney tubules, 3D gels are employed. Kidney tubules embedded within 3D gels are difficult to access for manipulations and imaging. Here we show how large and functional human kidney tubules can be generated in vitro on 2D surfaces, without the use of 3D matrices. The mechanism used by human primary renal proximal tubule cells for tubulogenesis on 2D surfaces appears to be distinct from the mechanism employed in 3D gels, and tubulogenesis on 2D surfaces involves interactions between epithelial and mesenchymal cells. The process is induced by transforming growth factor-beta(1), and enhanced by a 3D substrate architecture. However, after triggering the process, the formation of renal tubules occurs with remarkable independence from the substrate architecture. Human proximal tubules generated on 2D surfaces typically have a length of several millimetres, and are easily accessible for manipulations and imaging, which makes them attractive for basic research and in vitro nephrotoxicology. The experimental system described also allows for in vitro studies on how primary human kidney cells regenerate renal structures after organ disruption. The finding that human kidney cells organize tissue-like structures independently from the substrate architecture has important consequences for kidney tissue engineering, and it will be important, for instance, to inhibit the process of tubulogenesis on 2D surfaces in bioartificial kidneys. PMID- 20586830 TI - Engineered heart tissue graft derived from somatic cell nuclear transferred embryonic stem cells improve myocardial performance in infarcted rat heart. AB - The concept of regenerating diseased myocardium by implanting engineered heart tissue (EHT) is intriguing. Yet it was limited by immune rejection and difficulties to be generated at a size with contractile properties. Somatic cell nuclear transfer is proposed as a practical strategy for generating autologous histocompatible stem (nuclear transferred embryonic stem [NT-ES]) cells to treat diseases. Nevertheless, it is controversial as NT-ES cells may pose risks in their therapeutic application. EHT from NT-ES cell-derived cardiomyocytes was generated through a series of improved techniques in a self-made mould to keep the EHTs from contraction and provide static stretch simultaneously. After 7 days of static and mechanical stretching, respectively, the EHTs were implanted to the infarcted rat heart. Four weeks after transplantation, the suitability of EHT in heart muscle repair after myocardial infarction was evaluated by histological examination, echocardiography and multielectrode array measurement. The results showed that large (thickness/diameter, 2-4 mm/10 mm) spontaneously contracting EHTs was generated successfully. The EHTs, which were derived from NT-ES cells, inte grated and electrically coupled to host myocardium and exerted beneficial effects on the left ventricular function of infarcted rat heart. No teratoma formation was observed in the rat heart implanted with EHTs for 4 weeks. NT-ES cells can be used as a source of seeding cells for cardiac tissue engineering. Large contractile EHT grafts can be constructed in vitro with the ability to survive after implantation and improve myocardial performance of infarcted rat hearts. PMID- 20586832 TI - Leisure-time physical activities for community older people with chronic diseases. AB - AIMS: (1) To explore the types and three components (frequency, duration and caloric expenditure) of leisure-time physical activity in community older people with chronic diseases. (2) To identify leisure-time physical activity-related factors in these community older people. BACKGROUND: Previous research has focused primarily on measuring the actual physiological or psychological benefits of exercise or leisure-time physical activity, little is known about the factors that determine the frequency, intensity and duration of exercise or leisure-time physical activity. The identification of reliable predictors of the various components of leisure-time physical activity will enable healthcare providers to intervene and change the patterns of leisure-time physical activity in the sedentary older people more effectively. DESIGN: A cross-sectional design was used for this study. METHODS: Participants were recruited from the Xinyi District in Taipei, Taiwan. A total of 206 older people were recruited and were asked to complete three questionnaires during a face-to-face interview with a researcher at the activity setting. RESULTS: The results showed that walking leisurely was the most frequent leisure-time physical activity for participants. The age, gender, living arrangement, affective feeling and environmental control were significant variables of leisure-time physical activity. CONCLUSIONS: The study constructs accounted for moderate amounts of variance (22% for leisure-time physical activity frequency, 27% for leisure-time physical activity duration and 24% for leisure-time physical activity caloric expenditure). This study also showed that different variables play different influential roles in the different components of LTPA. RELEVANCE TO CLINICAL PRACTICE: An effective intervention strategy for improving leisure-time physical activity of older people may involve tailoring the type, format, intensity, frequency and duration of a physical activity according to an individual's needs. This study described some environmental barriers to LTPA and recommended an increase in the accessibility to LTPA areas. PMID- 20586833 TI - Promoting a continuation of self and normality: person-centred care as described by people with dementia, their family members and aged care staff. AB - AIMS AND OBJECTIVES: This article aims to describe the content of person-centred care as described by people with dementia, family members and staff in residential aged care. BACKGROUND: Person-centred care is increasingly being regarded as synonymous with best quality aged care; however, studies exploring stakeholders' experiences of person-centred care are few. DESIGN: A qualitative explorative design was employed using conversational research interviews and content analysis. METHOD: Research interviews were conducted in 2007 and 2008 with staff working in aged care (n = 37), people with early onset dementia (n = 11), and family members of patients with dementia (n = 19) and were analysed using content analysis. RESULTS: The findings indicated that the core category of person-centred care was promoting a continuation of self and normality. Five content categories emerged as contributing to promoting a continuation of self and normality: knowing the person; welcoming family; providing meaningful activities; being in a personalised environment; and experiencing flexibility and continuity. CONCLUSIONS: This study describes person-centred care as it is understood by people with dementia, their family members and staff in residential aged care, and as such it contributes with inside perspectives to current understandings of person-centred care, perspectives that have been largely lacking. Relevance to clinical practice. The findings of this study are clinically relevant and ready to be operationalised and applied in clinical aged care. The categories can be used as a topic guide for discussions in aged care organisations on the quality of current care and as elements indicating how to increase the person-centredness of care provided. PMID- 20586834 TI - Rosacea - global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group. AB - BACKGROUND: The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. OBJECTIVES: The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. METHODS: The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. RESULTS: New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein-5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein-5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy - the triad of rosacea care - that integrates patient education including psychological and social aspects, skin care with dermo-cosmetics as well as drug- and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. CONCLUSION: The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence-based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time. PMID- 20586835 TI - A novel complex insertion-deletion mutation in ADAR1 gene in a Chinese family with dyschromatosis symmetrica hereditaria. PMID- 20586836 TI - Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-alpha blocker agents: Report of five cases and review of the literature. AB - BACKGROUND: Tumour necrosis factor antagonists (anti-TNF-alpha) have demonstrated the efficacy in different chronic immune inflammatory disorders. Within the spectrum of adverse events, autoimmune diseases have been observed, including cases of alopecia areata (AA). OBJECTIVES: The objective of the study is to characterize AA developed during anti-TNF-alpha therapy. METHODS: We present five new cases and review all the cases reported in the literature (eleven). RESULTS: One third of the cases had a positive (personal or family) history of AA. Most of them presented with rapid extensive AA, usually involving the ophiasis area. Prognosis was usually poor, with slight response to treatments. In the cases where anti-TNF-alpha therapy was maintained, the course did not seem to change. CONCLUSIONS: Although rare, AA developed during anti-TNF-alpha therapy might be more frequent than suggested by reports of isolated cases. Personal and family history of autoimmune disease might alert clinicians to their possible development or relapse once the anti-TNF-alpha therapy is started. PMID- 20586837 TI - Mutation analysis of the ATP2A2 gene in Chinese patients with Darier's disease. PMID- 20586838 TI - PUVA plus interferon alpha2b in the treatment of advanced or refractory to PUVA early stage mycosis fungoides: a case series. AB - BACKGROUND: The combination of PUVA with variable doses of systemically administered interferon alpha2b (IFN-alpha2b) reduces the number of PUVA treatments and the dose of IFN-alpha2b required to produce remission in all mycosis fungoides (MF) stages. OBJECTIVES: To evaluate the efficacy of the combination of PUVA and IFN-alpha2b in patients with late stage or refractory to treatment early stage MF. METHODS: The combination of PUVA three times weekly and IFN-alpha2b 2-5 MU three times weekly was retrospectively reviewed in 22 patients. Kaplan-Meyer method and log-rank test was used for statistical analysis. RESULTS: Twenty-two patients were analysed, seven with refractory to PUVA early stage MF, seven with tumour stage, five with erythrodermic MF and three with Sezary syndrome (SS). The overall response rate (complete or partial response) was 68%, including 10 complete responses (CR) (45%) and five partial responses (PR) (23%). Significantly, more patients of the early stage group achieved CR compared with the advanced stage group (86% vs. 27%, P=0.03). Within the advanced stage group, CR rates were 14% vs. 37% in stage IIB and III/SS patients respectively, but the difference was not statistically significant. Patients with early stage disease had a 2-year PFS of 100% vs. 27% for the advanced stage group (P<0.001). Sustained remissions (>2 years) were achieved in five out of six complete responders in the early stage group of patients. CONCLUSION: This combination of IFN-alpha2b and PUVA is an effective and safe treatment for refractory to treatment early stage MF patients as well as treatment-naive advanced stage patients. Its efficacy is more pronounced in the former patient group. PMID- 20586839 TI - A role for regulatory focus in explaining and combating clinical inertia. AB - RATIONALE, AIMS AND OBJECTIVES: It is well established that clinical inertia generates suboptimal care in patients with chronic diseases, and policies and interventions have yet to satisfactorily address the problem. METHODS: This paper integrates the relevant literatures on clinical inertia and Regulatory Focus Theory (RFT) from psychology to identify an actionable explanatory mechanism. RESULTS: We review RFT and show that it provides a mechanism that may explain key provider contributions to clinical inertia. We then identify two general intervention strategies based on RFT: one that changes individual sensitivity to positive/negative outcomes and another that maintains the sensitivity to positive/negative outcome but frames how information is provided to match the sensitivity. CONCLUSIONS: We conclude that RFT is a plausible explanation to guide the development of policies and interventions for mitigating clinical inertia. PMID- 20586840 TI - Evaluation of the dissemination and implementation of pressure ulcer guidelines in Dutch nursing homes. AB - RATIONALE, AIMS AND OBJECTIVES: Annual national prevalence surveys have been conducted in the Netherlands over the past 10 years and have revealed high prevalence rates in Dutch nursing homes. Pressure ulcer guideline implementation is one of the factors that can influence prevalence rates. Previous research has shown that these guidelines are often only partly implemented in Dutch nursing homes. Reasons for this lack of pressure ulcer guideline implementation are not known. Therefore, the aim of this study is to investigate the current situation regarding pressure ulcer guideline dissemination and implementation in Dutch nursing homes. METHODS: Semi-structured interviews were conducted in eight nursing homes in the Netherlands from January till December 2008. In each nursing home, interviews were held with eight persons. RESULTS: The implementation of pressure ulcer guidelines was lacking in some of the nursing homes. Risk assessment scales were often not used in practice, repositioning schemes were not always available and, when they were, they were often not used in practice. Knowledge about guideline recommendations was also lacking and pressure ulcer education was inadequate. Barriers to applying guideline recommendations in practice were mostly related to personnel and communication. CONCLUSIONS: The implementation of pressure ulcer guidelines does not seem to be successful in all nursing homes and needs more attention. Barriers mentioned by the interviewees in applying guideline recommendations need to be addressed. Providing adequate education for nursing home staff and increasing attention for pressure ulcer care can be the first steps in improving the implementation of pressure ulcer guidelines. PMID- 20586841 TI - The electronic Cumulative Illness Rating Scale: a reliable and valid tool to assess multi-morbidity in primary care. AB - RATIONALE, AIMS AND OBJECTIVES: The presence of multiple concomitant diseases is an increasing health problem, and prompted by the limitations of the disease count, several indices measuring multi-morbidity or co-morbidity have been described to account for the overall burden of morbidity. The Cumulative Illness Rating Scale (CIRS) is one of those indices. We developed an electronic version of the CIRS (eCIRS) to take advantage of computerized data processing. The aim of this study was to evaluate the reliability and validity of the eCIRS scored in a primary care setting. METHODS: Two nurses interviewed 48 adult patients recruited during consecutive consultation periods in a primary care setting and scored the eCIRS in a random order during two sessions of data collection (T1 and T2) 1 month apart. We measured intra- and inter-rater reliability [intra-class correlation coefficient (ICC)]. We also assessed concomitant validity [(Pearson's correlation (r)] using standard CIRS scored by the attending family doctors. RESULTS: Intra-rater (ICC: 0.90 and 0.95) and inter-rater reliability (ICC: 0.86 and 0.91) were both excellent. No significant differences between the nurses' scores at T1 and T2 (P = 0.40 for nurse 1, P = 0.73 for nurse 2) were found. The eCIRSs scored by the nurses were highly correlated with the CIRSs scored by the doctors (r = 0.80 and 0.88). CONCLUSION: Reliable and valid, the eCIRS completed during patient interviews with trained nurses can be used to quantify multi morbidity in primary care, either for research or clinical use. PMID- 20586842 TI - Development of a consumer constructed scale to evaluate mental health service provision. AB - OBJECTIVE: Most mental health outcome and satisfaction measures have been developed by academic researchers or service providers. Consumers have been limited to the role of participant or advisor. The validity and reliability of these satisfaction measures have been challenged. This paper reports the development of a consumer satisfaction questionnaire in which consumers work as collaborative researchers to increase its face validity and relevance. METHOD: Eleven themes from a previous participatory study were used by consumer researchers and university-based researchers to generate questionnaire items, with four items reflecting each theme. The internal consistency and factor structure were examined in public and non-government mental health service centres based on data of 202 mental health consumers. RESULTS: Principal Components Analysis with oblique rotation yielded a two-factor structure: Empowerment and Dehumanization. The two factors together explained 36.7% of the total variance. The scale demonstrated high internal consistency, with Cronbach's alpha for the total scale at 0.92, and for the two factors at 0.92 and 0.80. CONCLUSIONS: The questionnaire was developed in accordance with an evaluation framework of consumer directed evaluation of mental health services. The final questionnaire consists of 26 items. It has satisfactory internal consistency and appeared to be useful with inpatients and outpatients. Further research will be performed to establish its test-retest reliability and criterion validity. PMID- 20586843 TI - Comparing simulation and threshold approaches when analysing data with probabilities of categories. AB - OBJECTIVE: Constructing categories based on probabilities is not unusual in defining the outcome or the exposure. We compare the threshold approach and the simulation approach in making inferences. METHOD: We used a simple structured example as well as published data to illustrate the difference between the simulation and the threshold approaches. RESULTS: We demonstrated that simulation results were different from the threshold approach in estimating the effect of a high-deductible health plan. For repeat visits, we estimated a statistically significant ratio of incident rate ratio (IRR) 0.78 (95% CI: 0.64, 0.93) for non preventable emergency department visits using the simulation approach while the high-severity category showed no statistical significance with the ratio of IRR 0.98 (95% CI: 0.64, 1.49) using a threshold of 75%. We also demonstrated that none of the threshold values could achieve the results of the simulation approach. CONCLUSIONS: The simulation approach is preferred over the threshold one when analysing data with probability-based outcome, exposure and/or other covariates if the size of the data permits. PMID- 20586844 TI - Antimicrobial prescribing in the USA for adult acute pharyngitis in relation to treatment guidelines. AB - RATIONALE, AIMS AND OBJECTIVES: American College of Physicians (ACP) published guidelines for the diagnosis and treatment of acute pharyngitis in adults in 2001. The objective of this study is to characterize antibiotic prescribing patterns in the USA for acute pharyngitis and evaluate concordance with the 2001 ACP pharyngitis treatment guidelines. METHODS: Patients aged >=18 years identified with acute pharyngitis via diagnosis codes (ICD-9 CM) were identified from data collected annually (1996-2006) by the National Center for Health Statistics and Centers for Disease Control and Prevention from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Total US office visits for acute pharyngitis were estimated. Logistic regression was performed to determine whether antibiotic prescribing was associated with the publishing of the ACP guidelines. RESULTS: A total of 3791 office visits met study criteria. We extrapolated 78.0 million visits for acute pharyngitis from 1996 to 2006. Antibiotics were prescribed in 62.6% of cases and 7.5% of cases received ACP-recommended antibiotics. There was a significant decrease in the rate of antibiotic prescriptions from 66.5% to 59.1% after publication of ACP guidelines. Univariate analysis showed that antibiotic prescribing decreased by 27% (OR = 0.73, 95% CI 0.55-0.95, P = 0.021). Multivariate analyses confirmed this finding (OR = 0.72, 95% CI 0.56-0.94, P = 0.014). The prescribing of ACP-recommended antibiotics did not significantly change (8.5% to 6.6%, P = 0.519). CONCLUSIONS: Publishing of ACP guidelines for the diagnosis and treatment of pharyngitis was associated with a decrease in the overall prescribing of antibiotics but not the prescribing of ACP-recommended antibiotics. PMID- 20586845 TI - The costs of guideline-concordant care and of care according to patients' needs in anxiety and depression. AB - AIM: To describe the direct and indirect costs for people with anxiety and depressive disorders where guidelines are adhered to and patients' perceived needs are fully met. METHOD: Data were derived from the Netherlands Study of Depression and Anxiety. At baseline, adult patients were interviewed and they completed questionnaires to measure DSM-IV diagnoses, socio-demographic characteristics and perceived need for care. Actual care data were also derived from electronic medical records. Criteria for guideline adherence were based on general practice guidelines, issued by the Dutch College of General Practitioners. Direct and indirect costs were inferred from the Perceived Need for Care Questionnaire administered at baseline, and the Trimbos and iMTA questionnaire on Costs associated with Psychiatric illness administered at 1-year follow-up. RESULTS: For 568 patients with a current anxiety or depressive disorder a complete dataset on health care use and absenteeism was available. Guideline adherence was significantly associated with increased care use and corresponding costs, while fully met perceived need was unrelated to costs. Socio demographic characteristics, severity of symptoms and guideline adherence all affected the societal costs of patients with fully met perceived needs compared with patients with perceived unmet needs. CONCLUSION: It appears that guideline concordant care for anxiety and depression costs more than non-concordant care, while care that has fulfilled all of a patient's needs seems not to be more expensive than care that has not met all perceived needs. However, randomized controlled trials should first confirm this conclusion. PMID- 20586847 TI - The quality of patient-orientated Internet information on oral lichen planus: a pilot study. AB - OBJECTIVE: This study examines the accessibility and quality Web pages related with oral lichen planus. METHODS: Sites were identified using two search engines (Google and Yahoo!) and the search terms 'oral lichen planus' and 'oral lesion lichenoid'. The first 100 sites in each search were visited and classified. The web sites were evaluated for content quality by using the validated DISCERN rating instrument. JAMA benchmarks and 'Health on the Net' seal (HON). RESULTS: A total of 109,000 sites were recorded in Google using the search terms and 520,000 in Yahoo! A total of 19 Web pages considered relevant were examined on Google and 20 on Yahoo! As regards the JAMA benchmarks, only two pages satisfied the four criteria in Google (10%), and only three (15%) in Yahoo! As regards DISCERN, the overall quality of web site information was poor, no site reaching the maximum score. In Google 78.94% of sites had important deficiencies, and 50% in Yahoo!, the difference between the two search engines being statistically significant (P = 0.031). Only five pages (17.2%) on Google and eight (40%) on Yahoo! showed the HON code. CONCLUSION: Based on our review, doctors must assume primary responsibility for educating and counselling their patients. PMID- 20586846 TI - Evaluation and economic impact analysis of different treatment options for ankle distortions in occupational accidents. AB - RATIONALE, AIMS AND OBJECTIVES: Appropriate use of diagnostic and treatment modalities are essential for rational use of resources. The aim of this study is to evaluate the use of diagnostic modalities and different treatment options and their economic impacts following an acute ankle distortion resulting from an occupational accident. We evaluated the type-of-treatment impact on the victims' course of recovery as well as its impact on the associated accident costs. Research was carried out in Belgium. METHODS: An ankle distortion victims' database consisting of 200 cases of (Belgian) occupational accidents during the period 2005-2007 was analysed. RESULTS: Patients who were prescribed immobilization or the use of adjuvant support or physical therapy (118 cases) were not employed during a period of 37 days on average, with a mean total cost of 3140.14 Euros caused by the ankle sprain. Patients without any adjuvant therapy (82 cases) were characterized by an unemployment rate of 15 days on average, and a total cost of 1077.86 Euros. Cast immobilization, although its application is not supported by evidence-based literature, was still applied in 36% of the population studied and resulted in the longest average absence of work of 42 days with an obvious significant increase in medical and total costs. CONCLUSIONS: Our results show a high rate of inappropriate use of cast immobilizations for ankle distortions. From an economic point of view and for the same clinical endpoint (being full resumption of the occupational activities), simple conventional treatment, consisting of rest, ice, compression and elevation at diagnosis with allowance of early weight bearing in the further clinical course, leads to the quickest full resumption of activities in combination with the lowest medical costs, if compared with any other kind of treatment. PMID- 20586848 TI - Dental and gastrointestinal changes as indicators of nutritional depletion in elderly inpatients. AB - OBJECTIVE: The objective of this study was to identify the associations between the nutritional status of elderly patients and length of hospital stay and presence of dental and gastrointestinal changes. CASUISTIC AND METHOD: This cross sectional study analyzed anthropometric and food intake indicators, dental and gastrointestinal changes and length of hospital stay of 441 elderly patients of both genders. The Pearson's correlation coefficient was used to verify the correlation between the nutritional status of the elderly patients and length of hospital stay and presence of dental and gastrointestinal changes. The significance level was set at P < 0.05. RESULTS: Dietary and anthropometric variables as well as length of hospital stay were similar for patients with and without dental changes. Patients with gastrointestinal changes consumed less energy (P < 0.05) than patients without gastrointestinal changes. Length of hospital stay was inversely correlated with body mass index (r = -0.15; P < 0.05); arm circumference was inversely correlated with presence of dental changes (r = -0.12; P < 0.05) and mid-arm muscle circumference was inversely correlated with gastrointestinal changes (r = -0.12; P < 0.05). CONCLUSION: Dental and gastrointestinal changes are important indicators of nutritional depletion and dietary intake of inpatients. PMID- 20586850 TI - Analysis of the microflora in the stomach of Mongolian gerbils infected with Helicobacter pylori. AB - BACKGROUND AND AIMS: Mongolian gerbils are frequently used to study Helicobacter pylori-induced gastritis and its consequences. The presence of some gastric flora with a suppressive effect on H. pylori suggests inhibitory microflora against H. pylori infection. The aim of the present study was to analyze the microflora in the stomach of Mongolian gerbils with H. pylori infection. METHODS: H. pylori ureA was detected by polymerase chain reaction (PCR) in the fecal samples of infected Mongolian gerbils. H. pylori was isolated from the gastric mucosa of the gerbils by microaerophilic cultivation. Gastric microflora were isolated by aerobic and anaerobic culture, and the identification of gastric bacterial species was performed by API20E and API20A. RESULTS: Oral administration of H. pylori TK1402 induced colonization and gastric inflammation of the stomach of the Mongolian gerbils. According to the frequency of detection of H. pylori ureA in fecal samples, the gerbils were divided into three groups (frequently detected, moderately detected and infrequently detected). According to the analysis of the gastric microflora in the frequently and infrequently detected groups, Lactobacillus spp. and Eubacterium limosum were isolated from the former and latter group, respectively. CONCLUSION: Some gastric flora, such as Lactobacillus spp., may inhibit colonization by H. pylori. PMID- 20586849 TI - Suppression of lymphangiogenesis induced by Flt-4 antibody in gastric low-grade mucosa-associated lymphoid tissue lymphoma by Helicobacter heilmannii infection. AB - BACKGROUND AND AIMS: Our recent study revealed that per oral infection with Helicobacter heilmannii induced low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric fundus of C57BL/6 mice after a period of 6 months, although the pathophysiological mechanism of lymphoma expansion remains to be clarified. The present study was undertaken to elucidate the interaction of this tumor with angiogenesis and lymphangiogenesis. In addition, the effect of Flt-4 antibodies on lymphoma expansion was investigated. METHODS: C57BL/6 female mice infected with H. heilmannii for 3 months were used in the experiments. Localization of vascular endothelial growth factor C (VEGF-C) and Flt-4 immunoreactivity were detected by indirect immunohistochemical methods. Localization of lymphatic and vascular endothelial cells was investigated by localization of prox-1. In addition, Flt-4 antibody with and without Flt-1 or Flk 1 antibodies was administered i.p. to clarify their effects on tumor size. RESULTS: MALT lymphoma has a rich microvascular network consisting of immature capillaries, lymphatics and venules. By immunohistochemical analysis, prox-1 immunoreactivity was observed mostly in the marginal area of the lymphoma, where VEGF-C and Flt-4 immunoreactivities were also seen. Stereomicroscopic study revealed that administration of Flt-4 and Flt-1 antibodies significantly reduced the surface area of the lymphoma in the mouse stomach. CONCLUSION: A VEGF-C mediated mechanism plays an important role in the expansion of MALT lymphoma and the administration of VEGF receptor antibodies had a suppressive effect on tumor growth. PMID- 20586851 TI - Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen-induced small intestinal lesions in rats. AB - BACKGROUND AND AIMS: We examined the effect of lafutidine, a histamine H(2) receptor antagonist with a mucosal protective action mediated by capsaicin sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats. METHODS: Animals were given loxoprofen (10-100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16 dimethyl prostaglandin E(2) (dmPGE(2); 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after. RESULTS: Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE(2) and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN. CONCLUSION: Lafutidine protects the small intestine against loxoprofen induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion. PMID- 20586852 TI - Investigation of gastroduodenal mucosal injuries caused by low-dose aspirin therapy in patients with cerebral infarction. AB - BACKGROUND AND AIMS: Low-dose aspirin is used as a preventive treatment for ischemic heart disease and ischemic cerebrovascular disease, on the other hand gastrointestinal injuries are an adverse effect of aspirin. We reported that endoscopic surveillance reveals a high risk of gastroduodenal ulcer and erosion in aspirin users of ischemic heart disease. But risk of gastroduodenal injuries may be different among pre-existing disease. In the present study, endoscopic examination was performed to investigate the frequency of gastroduodenal injuries associated with low-dose aspirin in patients with cerebrovascular disease. METHODS: Routine examination using upper gastrointestinal tract endoscopy was prospectively performed for all patients admitted to Sasson Hospital for rehabilitation after cerebral infarction from April 2005 to September 2007. Endoscopic findings such as ulcers and flat erosions were assessed as mucosal injuries. RESULTS: Endoscopic examination was performed for 142 successive patients, divided into three groups: 70 patients as low-dose aspirin users (aspirin group); 61 as non-aspirin users (non-aspirin group); and 11 as multi drug users of aspirin plus other anti-platelet drugs (combination group). The aspirin group without anti-ulcer drugs (A(-) group) comprised 47 patients and the non-aspirin group without anti-ulcer drugs (NA(-) group) 31 patients. Mucosal injuries were detected in 29.8% of the A(-) group and in 6.4% of the NA(-) group (P < 0.05). The frequency of ulcer was similar between the A(-) group (6.4%) and NA(-) group (3.2%). CONCLUSION: Endoscopy reveals low-dose aspirin-induced gastroduodenal injuries in patients with cerebral infarction. PMID- 20586853 TI - Observational comparative trial of the efficacy of proton pump inhibitors versus histamine-2 receptor antagonists for uninvestigated dyspepsia. AB - BACKGROUND AND AIMS: It is still controversial which drugs, proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA), are more effective for dyspepsia in the Japanese population. METHODS: Patients with uninvestigated dyspepsia (n = 104; male/female 41/63) were treated with either rabeprazole 10 mg o.d. (n = 62) or lafutidine 10 mg b.i.d. (n = 42) for 4 weeks. Questionnaires (modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease [mFSSG] and quality of life [QOL], SF-8) were administered before and after therapy. The mFSSG was classified into a total score (Q-T), reflux score (Q-R), dyspepsia score (Q-D) and pain score (Q-P). The SF-8 had a physical component summary (PCS) and mental component summary (MCS). The predominant type of symptom was reflux (R-S), pain (P-S) or dysmotility (D-S). RESULTS: R-S was 19.2%, P-S 48.1%, D-S 24.0% and overlap 8.7%. In the R-S, Q-T and Q-R significantly improved with rabeprazole, but neither scale improved with lafutidine. MCS significantly improved with rabeprazole. In P-S, Q-T, Q-R, Q-D and Q-P significantly improved with both drugs. PCS significantly improved with both, whereas the MCS significant improved with rabeprazole. In D-S, Q-R and Q-D significant improved with rabeprazole, but neither improved with lafutidine. QOL did not improve with either. With overlap, neither scale nor the QOL reached a significant difference. CONCLUSION: Both PPI and H2RA have a positive effect on P-S, but H(2)RA therapy is limited for R-S and D-S, whereas PPI therapy is generally effective. Therefore, careful prescription based on symptoms is important. PMID- 20586854 TI - Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis. AB - BACKGROUND AND AIMS: MicroRNA (miRNA) are endogenous, approximately 22-nucleotide non-coding RNA that suppress gene expression at post-transcriptional levels by binding to the 3'-untranslated region of specific mRNA targets through base pairing. It has been recently reported that miRNA have critical functions in key biological processes such as cell proliferation and cell death in various cancer cells. However, the relationship between intestinal inflammation and miRNA expression remains unclear. In the present study, we used microarray technology to identify miRNA induced in the colonic mucosa of patients with active ulcerative colitis (UC). METHODS: Two colonic biopsy specimens from patients with active stage (>Matts grade 2) of UC under colonoscopy and two colonic biopsy specimens from healthy volunteers were obtained for gene expression profiles. Total RNA was extracted, and miRNA expression profiles were investigated using miRNA Microarray. Subsequently, to confirm the result of the Microarray investigation, we checked the expression of several selected miRNA using real time polymerase chain reaction (PCR) in 12 colonic biopsy specimens from patients with active UC under colonoscopy and 12 specimens from the healthy volunteers. RESULTS: In the microarray study, the expression of several miRNA was upregulated in the colonic mucosa of patients with active UC. Furthermore, two miRNA (miR-21, miR-155) were selected in the study using real-time PCR. CONCLUSION: Upregulated miRNA may be responsible for the development of intestinal inflammation in UC. PMID- 20586855 TI - Enteral nutrition decreases hospitalization rate in patients with Crohn's disease. AB - BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease with relapse and remission. CD patients are admitted to hospital when bowel inflammation flares up severely, which lowers their quality of life. Enteral nutrition (EN) with an elemental diet plays an important role in the treatment for CD patients in Japan, because of its few adverse effects, and it is thought to be effective in maintaining remission. We investigated the effectiveness of EN with an elemental diet with regard to the avoidance of hospitalization. METHODS: A total of 268 patients with CD who visited hospital from 2003-2008 were enrolled. The relationship between the caloric content of an elemental diet and hospitalization as an end-point was examined retrospectively using Cox regression analysis. Cumulative non-hospitalization rates were calculated by the Kaplan Meier method. RESULTS: Of the 268 patients, 155 received an elemental diet providing 900 kcal/day or more. Among 237 patients with ileal involvement, 135 patients receiving an elemental diet providing 900 kcal/day or more showed a statistically significant improvement in cumulative non-hospitalization rate. Among 31 patients without ileal involvement, in contrast, the cumulative non hospitalization rate did not differ among those receiving an elemental diet of less or more than 900 kcal/day. CONCLUSION: The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long-term convalescence of these patients. PMID- 20586856 TI - Spectra of functional gastrointestinal disorders diagnosed by Rome III integrative questionnaire in a Japanese outpatient office and the impact of overlapping. AB - BACKGROUND AND AIMS: The aim of this study was to establish the spectra of functional gastrointestinal disorders (FGID) in a Japanese outpatient office in Rome III. METHODS: The Rome III Diagnostic Questionnaire for Adult Functional GI Disorders was translated into Japanese and an automated analyzing program was made according to the scoring algorithm of the questionnaire. Among 1378 patients who visited the outpatient office of the Social Insurance Shiga Hospital between May 2007 and April 2009, 112 serial patients who had symptoms possibly originating from the gastrointestinal (GI) tract, but did not have evidence of organic disease, were recruited. The subjects answered the questionnaire, and the answers were analyzed with the automatic analyzer. RESULTS: During the study period, 94 of the 112 patients were diagnosed as having active FGID. Non overlapping FGID was diagnosed in 41 (43.6%) of those. Of the 41 non-overlapping FGID patients, the most frequent diagnosis was irritable bowel syndrome (IBS) in 13 patients. Including overlapping cases, 165 FGID were diagnosed in 94 patients. The most frequent diagnosis was IBS in 33 patients (35.1%), the second was functional dyspepsia (FD) in 29 (30.9%) and the third was functional constipation in 21 (22.3%). The most frequent FGID overlapping with IBS was FD (36.4%), and the most frequent FGID overlapping with FD was IBS (41.4%). Of the 29 FD patients, 20 (69.0%) had functional bowel disorders. CONCLUSION: The most frequent FGID was IBS in both overlapping and non-overlapping FGID patients. IBS and FD were the most frequent combinations in overlapping FGID. Most cases of FD are possibly parts of functional bowel disorders. PMID- 20586857 TI - Identification of inflammation-related proteins in a murine colitis model by 2D fluorescence difference gel electrophoresis and mass spectrometry. AB - BACKGROUND AND AIMS: The aim of this study was to identify new intestinal proteins potentially associated with acute inflammation using proteomic profiling of an in vivo mice model of ulcerative colitis. METHODS: 2D fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight spectrometer (MALDI-TOF) peptide mass fingerprinting were used to determine differentially expressed proteins between normal and inflamed intestinal mucosa. Acute colitis was induced by 8.0% dextran sodium sulfate (DSS) given p.o. for 7 days. RESULTS: Among a total of seven protein spots showing differential expression, we identified five different proteins, of which two were upregulated and three downregulated in colitis in comparison to normal mucosa, using the MASCOT search engine. 3-Hydroxy-3 methylglutaryl-coenzyme A synthase 2 and serpin b1a were upregulated proteins, and protein disulfide-isomerase A3, peroxiredoxin-6 and vimentin were identified as downregulated proteins. CONCLUSION: These identified proteins may be responsible for the development of the intestinal inflammation. 2D-DIGE and MALDI TOF mass spectrometry are useful in the search for the differentially expressed proteins. PMID- 20586858 TI - Colonoscopic differences of erosive and/or small ulcerative lesions for diagnosis of colonic inflammatory diseases. AB - BACKGROUND AND AIMS: Various etiologies and diseases may be related to erosive and/or small ulcerative lesions without gross appearance in the colon during colonoscopy. However, few investigators report on differential diagnosis of colonic inflammatory diseases. Thus, we investigated the clinical significance of these lesions and the value of colonoscopy in the differential diagnosis of colitis. METHODS: In 110 patients with erosive and/or small ulcerative lesions (<5 mm) who were treated in our hospital during the past 9 years, we retrospectively investigated the relationship between endoscopic morphology and clinical diagnosis. The intestinal lesions were endoscopically classified into three groups (A, hyperemic type; B, aphthous type; and C, verrucous type). RESULTS: The lesions were mainly located in the rectum to the sigmoid colon in group A. In group C, the lesions were most frequently located in the transverse colon and deeper areas. Endoscopically, the etiology was unclear in 74.5% of group A and 73.8% of group B, however, in group C, most of them (81.0%) were associated with specific diseases. With respect to inflammatory bowel diseases, 71.4% of the patients with Crohn's disease and all patients with ulcerative colitis were assigned to group A or B. CONCLUSION: Erosive and/or small ulcerative lesions belonging to group A or B were mainly non-specific. However, careful follow up was required in groups A and B, which included the possibility of inflammatory bowel diseases, when the symptoms or lesions were not improved. PMID- 20586859 TI - New method of inducing intestinal lesions in rats by intraduodenal administration of aspirin. AB - BACKGROUND AND AIMS: Enteroscopic observation has clearly demonstrated that non steroidal anti-inflammatory drugs/low-dose aspirin (usually enteric-coated) induces hemorrhagic lesions, including ulcers and bleeding, in the small intestine of patients at a high incidence. Such intestinal lesions induced by NSAIDs have been confirmed in animal experiments. With aspirin, however, it has long been believed that it is difficult to induce any damage in the intestinal mucosa of laboratory animals. Therefore, we established a new method of inducing intestinal hemorrhagic lesions in rats by injecting aspirin into the proximal duodenum. METHODS: Under ether anesthesia, aspirin (50-200 mg/body), suspended in 2% methylcellulose (with or without 0.1 N HCl), was injected into the proximal duodenum of normally fed or 20-h non-fed rats (male Sprague-Dawley, 9 weeks old). At 1 h after treatment, the animals were killed with ether and the entire small intestine was removed for histological examination. In some experiments, 1% Evans blue was injected (i.v.) into the rats 1 h after aspirin treatment to visualize the lesions. An image analyzer determined the total area of the intestinal lesions. Oral proton pump inhibitors and histamine H(2)-receptor blockers were given 1 h before aspirin injection. 16,16-dimethyl prostaglandin E(2) (dmPGE(2)) was given s.c. 30 min before aspirin injection. RESULTS: Aspirin alone clearly induced severe lesions (including bleeding and ulcers) mainly in the jejunum at 100% incidence. Total score of lesions per rat obtained by histological examination was similar to the damaged area quantified with the dye method. Dose related induction of lesions by aspirin was confirmed both by the histological and dye methods. The irritable effect of aspirin suspended in 0.1 N HCl solution was the same as that of aspirin alone; 0.1 N HCl alone induced only minor lesions in the intestine. Both proton pump inhibitors and histamine H(2)-receptor blockers, at doses that inhibit gastric acid secretion, had no or little effect on aspirin-induced intestinal lesions. Pretreatment with dmPGE(2) (3, 10, 30 microg/kg) showed significant prevention of both aspirin- and HCl/aspirin-induced intestinal lesions. CONCLUSION: This new aspirin lesion model will be useful for screening defensive drugs against aspirin-induced intestinal lesions and to elucidate the underlying mechanism. PMID- 20586860 TI - Sofalcone, a gastroprotective drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori: a randomized controlled comparative trial with cimetidine, an H2-receptor antagonist. AB - BACKGROUND AND AIMS: According to reports in Japanese patients, 1 week of Helicobacter pylori eradication therapy alone is not adequate for healing of gastric ulcers; 7-8 weeks of anti-ulcer therapy are subsequently required. We compared a gastroprotective drug, sofalcone, and an H(2)-receptor antagonist, cimetidine, in terms of promoting ulcer healing after 7 weeks of administration following 1 week of eradication therapy. METHODS: Eradication therapy was administered to 64 patients with H. pylori-positive active gastric ulcer at least 10 mm in diameter, after which 32 patients each received 7 weeks of ulcer treatment with sofalcone (300 mg/day) or cimetidine (800 mg/day). RESULTS: The H. pylori eradication rate was 81.3% (intention-to-treat: ITT) and 81.3% (per protocol: PP) in the sofalcone group, and 62.5% (ITT) and 64.5% (PP) in the cimetidine group. The ulcer healing rate after 8 weeks was 71.9% (ITT) and 71.9% (PP) in the sofalcone group, and 71.9% (ITT) and 71.0% (PP) in the cimetidine group. The rate of a flat pattern of scarred mucosa was 43.5% (ITT) and 43.5% (PP) in the sofalcone group, and 47.8% (ITT) and 50.0% (PP) in the cimetidine group. No significant differences were seen between the two groups in terms of H. pylori eradication rate, ulcer healing rate and flat pattern rate. CONCLUSION: Sofalcone promoted gastric ulcer healing during 7 weeks of treatment following 1 week of eradication therapy, and the healing rate was equivalent to that of cimetidine. Symptom disappearance rates were significantly better in the sofalcone group than in the cimetidine group. This may be a useful way of using a gastroprotective drug in the H. pylori era. PMID- 20586861 TI - Impact of upper gastrointestinal lesions in patients on low-dose aspirin therapy: preliminary study. AB - BACKGROUND AND AIMS: We investigated the incidence of upper gastrointestinal lesions in the esophagus, stomach and duodenum in patients on low-dose aspirin (LDA) therapy. METHODS: The subjects were 101 consecutive outpatients who had been on LDA therapy (average age 67.2 +/- 8.3 years; male : female ratio 3.8:1). All subjects underwent endoscopy without ceasing their antiplatelet or anticoagulant therapy. We investigated the rates of endoscopic peptic ulcer, reflux esophagitis (RE) and malignant lesion. RESULTS: RE was detected in eight subjects and esophageal ulcer in one subject. The severity of RE, according to the Los Angeles classification, was grade A in one subject, B in four, C in two and D in one. All nine subjects (8.9%) with RE and esophageal ulcer were negative for Helicobacter pylori infection. Gastric ulcer was detected in 12 subjects (six H. pylori positive, six negative) and duodenal ulcer in four (one H. pylori positive, three negative). The incidence of gastroduodenal ulcer was 15.8% (16/101). The incidence of esophageal and gastric cancers was high at 5.9% (6/101). Subjects were surveyed using the gastrointestinal symptom rating scale, with no differences in scores for acid reflux, abdominal pain or indigestion according to the presence or absence of RE, gastric ulceration or duodenal ulceration. CONCLUSION: Upper gastrointestinal mucosal injuries and neoplasm were found in not only the stomach, but also the esophagus and duodenum in LDA taking subjects. These results emphasize the importance of endoscopic surveillance in patients on LDA therapy. PMID- 20586862 TI - Aspirin-induced peptic ulcer and genetic polymorphisms. AB - There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1 1676T alleles was a significant risk factor for peptic ulcer in users of non steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required. PMID- 20586863 TI - Protective effect of roxatidine against indomethacin-induced small intestinal mucosal injury in rats. AB - BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most significant causative factors of gastroduodenal ulcers. Recent reports have demonstrated that NSAIDs can also frequently induce ulceration and erosions of the small intestine. The aim of this study was to examine whether or not roxatidine (an H(2) receptor antagonist), which is known to increase gastric mucus in addition to inhibiting gastric acid, might suppress indomethacin-induced small intestinal mucosal injury, through an increase in mucus in rats. METHODS: Rats were given two p.o. doses of roxatidine, famotidine or cimetidine before and after the s.c. indomethacin injection. The injured area of the small intestine was analyzed. To examine effects of drugs on small intestinal mucus, rats were also given two p.o. doses of roxatidine, famotidine or cimetidine, and the ratio of the periodic acid Schiff (PAS)-positive area to the area of the mucosa in the small intestine was analyzed. In addition, we evaluated the involvement of nitric oxide (NO) and prostaglandins (PG) in the effect of roxatidine on small intestinal mucus. RESULTS: Roxatidine significantly ameliorated indomethacin induced small intestinal injury and increased the PAS-stained areas in the small intestinal mucosa, while cimetidine and famotidine had no significant effect. Pretreatment with N-nitro-L-arginine methyl ester but not with indomethacin, suppressed the effect of roxatidine on small intestinal mucus, suggesting that the effect is mediated by endogenous NO but not by PG. CONCLUSION: Roxatidine suppressed indomethacin-induced small intestinal injury in rats. One possible mechanism is an increase of small intestinal mucus, mediated by NO. PMID- 20586864 TI - Effect of gastroesophageal reflux disease on sleep. AB - Recent studies have demonstrated a bidirectional relationship between gastroesophageal reflux disease (GERD) and sleep where night-time reflux leads to sleep deprivation and sleep deprivation per se can exacerbate GERD by enhancing perception of intra-esophageal stimuli. Presently, treatment has primarily focused on reducing night-time reflux and thus improving sleep quality. Future studies are needed to further explore the relationship between GERD and sleep and the potential of novel therapeutic options to interrupt the vicious cycle between GERD and sleep. PMID- 20586865 TI - Abdominal ultrasonography as a new modality for the diagnosis of gastroesophageal reflux disease. AB - BACKGROUND AND AIMS: Thickening and abnormal architecture of the esophageal wall in gastroesophageal reflux disease (GERD) have been reported using endoscopic ultrasonography (US), but whether extracorporeal abdominal US is a useful diagnostic modality has not been investigated. METHODS: Subjects were 37 GERD, 24 non-erosive reflux disease (NERD) patients and 32 controls who visited our hospital from 2006-2009 and underwent upper gastrointestinal endoscopy and extracorporeal abdominal US. The US operator was unaware of any clinical information and examined the following: (i) thickness (>or=5 mm) and (ii) architecture of the esophageal wall; and (iii) presence of reflux. GERD was diagnosed when two or more of these items were positive. RESULTS: Thickening of the lower esophageal wall in erosive GERD, NERD and controls was 5.7 +/- 0.6, 4.4 +/- 0.8 and 4.7 +/- 0.9 mm, respectively. The thickness in erosive GERD was significantly greater (P < 0.05) than that in NERD patients and controls. Sensitivity, specificity and accuracy of abdominal US diagnosis for erosive GERD and NERD (vs control) was 84.6% (11/13), 25% (6/24), 91.1% (31/34) and 91.1% (31/34), 89.4% (42/47) and 63.8% (37/58), respectively. CONCLUSION: Extracorporeal abdominal US could be a new useful modality for diagnosing GERD. PMID- 20586866 TI - Colorectal cancer screening in evolution: Japan and the USA. AB - Colorectal cancer (CRC) is one of the most common cancers in both Japan and the USA. Age-adjusted incidence of CRC has been in decline in the USA since 1985, while rates in Japan have been increasing. The decline in the USA is commonly attributed to CRC screening programs but there is little direct evidence to support this assertion. The current screening recommendations in the USA cover several options including colonoscopy and computerized tomographic colonography (CTC). The Japanese CRC screening program is centered on fecal immunochemistry testing (FIT). The US government Medicare program's approval of colonoscopy as a primary screening test has lead to a large increase in the number of patients undergoing the procedure. However, the benefit achieved from this change in screening program emphasis is not clear. Simulation models demonstrate that a screening program centered on FIT achieves 94% of the benefit that an all colonoscopy program is able to accomplish but at a lower cost per life year gained. Clinical studies of colonoscopy have failed to demonstrate the 76-90% declines in CRC incidence predicted by the National Polyp Study published in 1993. A potential reason for this failure is the quality of colonoscopy performance. Until more compelling data becomes available demonstrating the utility of colonoscopy as a primary screening modality, there is little incentive to alter the proven cost-effective approach to CRC screening currently in practice in Japan. PMID- 20586867 TI - Clinicopathological characteristics of colorectal cancer less than 10 mm in diameter and invading submucosa and below. AB - BACKGROUND AND AIMS: Identifying the invasive depth of cancers less than 10 mm in diameter remains a challenge. This study examines the clinicopathological characteristics of colorectal cancers less than 10 mm in diameter and invading submucosal layer (SM)3 and below, which require surgery and must never be treated by endoscopic mucosal resection. METHODS: We studied 54 cases of colorectal cancer less than 10 mm in diameter and invading the submucosa and deeper tissues, by dividing them into two groups: those invading SM1 and SM2 versus those invading SM3 and below. We investigated the clinicopathological characteristics of cancers invading SM3 and below by comparing them with cancers invading SM1 and SM2. Similarly, 38 cases, whose endoscopic findings could be analyzed, were selected and examined. RESULTS: In cases invading SM3 and below, the rates of moderately to poorly differentiated adenocarcinoma, lymphatic and venous permeation and lymph node metastasis were significantly higher than those invading SM1 and SM2. Among cases invading SM3 and below, the presence of endoscopic findings-including white spots of the protruded type, and fullness, white spots, hardness and protruded lesions in the depressed area of the depressed type-was significantly higher than among those invading SM1 and SM2. CONCLUSION: Colorectal cancers less than 10 mm in diameter and invading SM3 and below have high malignant potential. Cancers of this invasive depth can be identified by looking for characteristics such as white spots, fullness, hardness and protruded lesions in the depressed area. Careful endoscopic observation for these signs aids in determining the appropriate treatment. PMID- 20586868 TI - Efficacy of antibiotic combination therapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases. AB - BACKGROUND AND AIMS: We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Herein, we assessed whether antibiotic combination therapy is effective for active UC, including cases with steroid refractory or dependent disease. METHODS: We enrolled 25 patients with active UC including 17 steroid dependent or refractory cases. These patients received amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. for 2 weeks as well as conventional treatment. Seven colonic segments from the appendiceal region to the rectum were scored for endoscopic activity and histology. Clinical activity indexes (CAI) were also determined. RESULTS: At 3 and 12 months after antibiotic treatment, CAI and endoscopic score were significantly decreased as compared to those before treatment (P < 0.001 and P < 0.05, P < 0.01, respectively). Histological scores were also significantly decreased at 12 months as compared to before treatment (P < 0.01). The clinical response rates in steroid-dependent patients were 60% and 73.3% at 3 and 12 months, respectively, while being 50% at 12 months in steroid-refractory patients. Among the 17 steroid-dependent or refractory patients, 12 (70.6%) were able to discontinue steroid therapy at 12 months. No serious drug-related toxicities were observed during the trial. CONCLUSION: This long-term follow-up study suggests 2-week antibiotic combination therapy to be effective and safe in patients with active UC including those with steroid-refractory or dependent disease. PMID- 20586869 TI - Endogenous prostaglandin E2 accelerates healing of indomethacin-induced small intestinal lesions through upregulation of vascular endothelial growth factor expression by activation of EP4 receptors. AB - BACKGROUND AND AIMS: The effects of an EP4 agonist/antagonist on the healing of lesions produced by indomethacin in the small intestine were examined in rats, especially in relation to the expression of vascular endothelial growth factor (VEGF) and angiogenesis. METHODS: Animals were given indomethacin (10 mg/kg s.c.) and killed at various time points. To impair the healing of these lesions, a small dose of indomethacin (2 mg/kg p.o.) or AE3-208 (EP4 antagonist: 3 mg/kg i.p.) was given once daily for 6 days after the ulceration was induced, with or without the co-administration of AE1-329 (EP4 agonist: 0.1 mg/kg i.p.). RESULTS: Indomethacin (10 mg/kg) caused severe damage in the small intestine, but the lesions healed rapidly decreasing to approximately one-fifth of their initial size within 7 days. The healing process was significantly impaired by indomethacin (2 mg/kg) given once daily for 6 days after the ulceration. This effect of indomethacin was mimicked by the EP4 antagonist and reversed by co administration of the EP4 agonist. Mucosal VEGF expression was upregulated after the ulceration, reaching a peak on day 3 followed by a decrease. The changes in VEGF expression paralleled those in mucosal cyclooxygenase-2 expression, as well as prostaglandin E(2) (PGE(2)) content. Indomethacin (2 mg/kg) downregulated both VEGF expression and angiogenesis in the mucosa during the healing process, and these effects were significantly reversed by co-treatment with the EP4 agonist. CONCLUSION: The results suggest that endogenous PGE(2) promotes the healing of small intestinal lesions by stimulating angiogenesis through the upregulation of VEGF expression mediated by the activation of EP4 receptors. PMID- 20586870 TI - Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy. AB - BACKGROUND AND AIMS: Resistance of Helicobacter pylori to the standard therapeutic antimicrobial agents has been demonstrated. Although quinolones are an alternative candidate for third-line eradication therapy, quinolone resistance of H. pylori is also increasing. Quinolone resistance of H. pylori is caused by a point mutation of the DNA gyrase subunit A (GyrA) protein, especially on amino acids 87 and 91. The aim of this study is to surmise the structure of H. pylori GryA. METHODS: The modeling of the 3-D structure of H. pylori GyrA was performed by an automated homology modeling program: SWISS-MODEL. The position of amino acids 87 and 91 in H. pylori GyrA was plotted on the homology model. To estimate the function of quinolone resistance-determining region (QRDR), the structure of H. pylori GyrA was compared with Escherichia coli GyrA. RESULTS: A molecular model of H. pylori GyrA could be predicted using SWISS-MODEL. The GyrA N- and C terminal domains closely resembled those of E. coli. The position of amino acids 87 and 91 in H. pylori GyrA was part of the DNA binding region (head dimer interface) on the GyrA N-terminal domain. CONCLUSION: Our homology model of H. pylori GryA suggests that the quinolone resistance-determining region is on the head dimer interface of the GyrA N-terminal domain. PMID- 20586871 TI - Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori. AB - BACKGROUND AND AIMS: Although clarithromycin (CLR) is one of the most commonly recommended component drugs of Helicobacter pylori eradication regimens, the prevalence of CLR-resistant H. pylori has been increasing. It is well known that CLR resistance is associated with point mutations in 23S rRNA, but an active multidrug efflux mechanism of H. pylori may also play a role in its drug resistance. At least four gene clusters have been identified as efflux pump systems in H. pylori and the present study was designed to investigate their role in the CLR resistance of clinical isolates of H. pylori. METHODS: Fifteen CLR resistant H. pylori strains (minimal inhibitory concentration [MIC]>or= 1 microg/mL) isolated from patients at Keio University Hospital were examined for expression of efflux pump mRNA by real-time polymerase chain reaction. In addition, the MIC of CLR in the presence or absence of Phe-Arg-beta-naphthylamide (PAbetaN), an efflux pump inhibitor (EPI), were determined. RESULTS: In all 15 strains, efflux pump mRNA was expressed, and the MIC of CLR were decreased by using EPI, despite possessing 23s rRNA point mutations. In addition, the MIC of CLR was decreased by the EPI in a concentration-dependent fashion. CONCLUSION: The efflux pump of H. pylori is associated with the development of resistance to CLR, in addition to 23S rRNA point mutations. Efflux pumps could be a novel target for reversing drug resistance in H. pylori. PMID- 20586872 TI - Helicobacter pylori infection and reflux esophagitis in young and middle-aged Japanese subjects. AB - BACKGROUND AND AIMS: Helicobacter pylori infection rates are reported to be high in people over the age of 40 years, but are decreasing in younger age groups. A negative correlation has been reported between H. pylori infection and reflux esophagitis (RE). METHODS: The subjects were 418 patients who underwent esophagogastroduodenoscopy and measurement of serum immunoglobulin G H. pylori antibodies examined as part of their routine health checks. Their mean age was 39.2 +/- 8.3 years (range 22-58). We analyzed the RE findings (Los Angeles classification: A, B, C, D). RESULTS: The total H. pylori infection rate was 33.7% (141/418). By age group, infection rates were 15.7% in the 20-29 years group, 28.0% in the 30-39 group, 34.3% in the 40-49 group and 69.1% in the 50-59 group. The proportion of H. pylori-negative subjects with RE was 23.5% (20-29, 22.9%; 30-39, 31.7%; 40-49, 32.4%; 50-59, 41.7%), significantly higher than that (12.1%) in H. pylori-positive subjects (20-29, 0%; 30-39, 16.7%; 40-49, 12.2%; 50 59, 10.5%). The severity of RE increased with advancing age in H. pylori-positive subjects, but not in H. pylori-negative subjects. CONCLUSION: In this study, higher rates of RE were seen in H. pylori-negative subjects. It may be, however, that the presence of H. pylori infection influences the progression of RE. PMID- 20586873 TI - Serological analysis of Helicobacter hepaticus infection in patients with biliary and pancreatic diseases. AB - BACKGROUND AND AIMS: Infection with Helicobacter hepaticus has been associated with development of hepatocellular carcinoma and gallstones in animal models. In humans, however, the association of H. hepaticus infection with biliary and pancreatic diseases has not been elucidated. The aim of this study was to serologically examine the prevalence of H. hepaticus infection in patients with biliary and pancreatic diseases. METHODS: Serum samples obtained from 55 patients with cholelithiasis, 18 with bile duct or gallbladder cancer and 19 with pancreatic cancer were studied. Sera were obtained from 34 control subjects who underwent endoscopy and were diagnosed as not having peptic ulcers or cancers. Seropositivity of H. hepaticus was examined by western blot analysis using a H. hepaticus-specific antigen. To validate the specificity, positive sera were also tested after absorption with H. hepaticus whole-cell sonicate. Serum samples were also tested for the presence of anti-Helicobacter pylori antibody. RESULTS: Prevalence of antibody to H. hepaticus-specific antigen in patients with bile tract cancer was 38.8% and was significantly higher than in control subjects (13.1%, P < 0.05). Prevalence of antibody to H. hepaticus-specific antigen was 18.2% and 10.5% in patients with cholelithiasis and pancreatic cancer, respectively. Seropositivity for H. pylori was similar in all groups. Detection of the H. hepaticus-specific band was significantly decreased after the sera were absorbed with H. hepaticus whole-cell sonicate. CONCLUSION: Infection with H. hepaticus might be associated with bile duct cancer. Results obtained from absorbed sera suggested high specificity of the western blot analysis. PMID- 20586874 TI - Assessment of in vitro biofilm formation by Helicobacter pylori. AB - BACKGROUND AND AIMS: Biofilms are surface-bound communities of bacterial cells that are implicated in their survival. As with various bacteria studied to date, Helicobacter pylori can have an alternate lifestyle as a biofilm. We previously reported that strain TK1402 showed a strong biofilm-forming ability in vitro. However, the mechanisms of its biofilm development remain unclear. We analyzed the basic characteristics of the biofilm-forming ability in strain TK1402. METHODS: In order to characterize the biofilm-forming ability of the H. pylori strains, auto-aggregation, motility and hydrophobicity, which are important factors in biofilm formation by other bacteria, were analyzed. Further, we tested whether cell growth participated in biofilm formation in strain TK1402. RESULTS: There were no significant differences in the auto-aggregation, motility and hydrophobicity of strain TK1402 compared with the other strains. On the other hand, pre-culture of this strain for 24-48 h resulted in decreased biofilm formation. CONCLUSION: TK1402 is a strong biofilm-forming strain of H. pylori in Brucella broth supplemented with 7% fetal calf serum. It is possible that biofilm forming cell growth is a principal factor in biofilm development. PMID- 20586875 TI - Restriction-modification systems may be associated with Helicobacter pylori virulence. AB - Restriction-modification (R-M) systems are exclusive to unicellular organisms and ubiquitous in the bacterial world. Bacteria use R-M systems as a defense against invasion by foreign DNA. Analysis of the genome sequences of Helicobacter pylori strains 26 695 and J99 identified an extraordinary number of genes with homology to R-M genes in other bacterial species. All H. pylori strains possess their own unique complement of active R-M systems. All of the methylases that have been studied so far were present in all major human population groupings, suggesting that their horizontal acquisition pre-dated the separation of these populations. The two most strongly conserved methylase genes of H. pylori, hpy IM and hpy IIIM, are both preceded by alternative genes that compete for presence at their loci, and furthermore these genes may be associated with H. pylori pathogenicity. Further study should investigate the roles of H. pylori R-M systems. PMID- 20586876 TI - Changes in the prevalence of Helicobacter pylori infection and gastrointestinal diseases in the past 17 years. AB - BACKGROUND AND AIMS: The aim of the study was to examine whether the change in the prevalence of Helicobacter pylori infection had influenced upper gastrointestinal diseases in a recent 17-year period. METHODS: The prevalence of H. pylori infection was examined by serum H. pylori antibody tests in the subjects undergoing annual health checks at the Social Insurance Shiga Hospital in 1998 and 2005 (142 and 242 subjects, respectively). The prevalence of H. pylori infection in 1988 was estimated by parallel translation from the prevalence in 1998. A total of 2833 records of endoscopy performed in 1988 and 2005 at Otsu Municipal Hospital were studied. The age-adjusted prevalence of peptic ulcer, gastric cancer and reflux esophagitis were compared between 1988 and 2005. RESULTS: The age-adjusted prevalence of H. pylori infection significantly decreased in 2005 compared with 1988 (70.5-52.7%). The endoscopic records of 937 and 1246 patients in 1988 and 2005, respectively, were included in the analysis. The age-adjusted prevalence of peptic ulcer significantly decreased 0.34-fold in both men and women in 2005 compared with 1988. The age-adjusted prevalence of gastric cancer significantly decreased 0.44-fold in men, but did not change in women (0.99-fold), and overall significantly decreased 0.56-fold. The age-adjusted prevalence of reflux esophagitis significantly increased 6.6-, 2.7- and 4.8-fold in men, women and total, respectively. The increase was dominant in men aged 30-69 years. CONCLUSION: Over the 17-year period, accompanying the decreasing prevalence of H. pylori infection, the age-adjusted prevalence of peptic ulcer and gastric cancer decreased, but that of reflux esophagitis increased. PMID- 20586877 TI - NSAID disorders in the esophagus, stomach and duodenum have been an important topic for a long time. Foreword. PMID- 20586879 TI - Introduction to Counterpoint. PMID- 20586880 TI - Counterpoints of care: two moments of struggle. AB - This paper examines the history of care in modern society and seeks to expose how deep transformations in care arise from wider social relations. From historical survey we may discern a series of transitional points, where the practice and the experience of care was greatly, sometimes suddenly, redefined. Each betrayed deeper political and ethical struggles that went to the core of social relations, and which weren't merely therapeutic in nature. This paper explores two such 'moments'. I first examine the emergence of a new institutional landscape during the middle industrial era, in the wake of a series of legal and political reforms that sought to settle a social order uprooted and distressed by raw modernisation. I provide a composite, yet incomplete view, of how this transformation proceeded in one urban setting, colonial Melbourne. In the second instance, I review the ambitions and process of deinstitutionalisation in the late 20(th) century. Ostensibly, this reform sought, inter alia, to collapse the great division between 'fit' and 'unfit' established in 1834. Again, empirical reference is made to the reconstitution of care in Melbourne, Australia, this time during its late 20th experience of institutional reform. The focus in this case is the process of downscaling and closure for a major congregate facility, Kew Cottages. The major conclusion is that periods of intense transition in the ideology and mode of care are reflective of wider social transformations not merely of therapeutic or institutional shifts. PMID- 20586881 TI - Mind the gap: MIND, the mental hygiene movement and the trapdoor in measurements of intellect. AB - BACKGROUND: The National Association for Mental Health adopted the 'brand name' MIND as part of its transformation into a campaigning pressure group at the turn of the 1970s. This article examines the historical antecedents to key statements made by the organisation at this time regarding the relationship of mental health with, what was then called, 'mental handicap'. METHODS: The National Association is placed within the historical context of the movement for mental hygiene. The article traces how the movement theorised mental health as critically related to intellect and emotionality. RESULTS: The movement relegated people deemed 'mentally deficient' from therapeutic policies based on family relationships believed to promote mental health. However, a late 1950s experiment known as the Brooklands study subverted this discrimination. This was paradoxical since it built on mental hygiene theorising. CONCLUSIONS: Theorisations of the relationship between intellect, emotion and mental health are still potentially discriminatory. PMID- 20586882 TI - The importance of tacit knowledge in practices of care. AB - BACKGROUND: The paper argues that a high quality personal relationship between professionals and clients is a necessary condition of professional knowledge. This epistemological claim is developed against the background of current methods of quality assessment that rely on objectively measurable 'indicators'. METHOD: A philosophical analysis regarding the nature of professional knowledge in the care sector. The analysis proceeds from Michael Polanyi's concept of tacit knowledge to account for the personal dimension of professional expertise in the care sector. RESULTS: Quantitative methods of quality assessment understand 'quality of care' as being independent from the professional who generates it. Consequently, quality assessment as currently practiced necessarily renders the personal dimension of professional knowledge invisible, thereby excluding it from managerial attention and support. To indicate the relevance of Polanyi's concept of tacit knowledge, the paper offers some observations from the practice of care in a group home for people with intellectual disabilities. CONCLUSION: The paper concludes that a high quality relationship between professionals and their clients is crucial for quality of care. This relationship generates the positive interaction that enables professionals to gain adequate insight in the needs of their clients. PMID- 20586883 TI - 'People who need people': attachment and professional caregiving. AB - From the perspective of attachment theory, this paper discusses individual differences in the quality of caregiving by direct-care staff for persons with intellectual disabilities. Theoretical arguments and findings from related literature are cited to support the probable role of professionals' own attachment experiences and their mental representations thereof. Case examples are drawn from a study on video-based interaction guidance for direct-care staff in group homes for persons with multiple, serious disabilities. These examples illustrate how interventions may avoid attachment-related defences against changing the quality and affective mutuality of personal contact with clients. However, the possibility is discussed that in parallel processes, quality management systems and institutional culture may selectively reinforce care patterns associated with insecure, dismissing attachment, while failing to reward the positive contribution that sensitive, affectively attuned caregiving makes to wellbeing of persons with disabilities. PMID- 20586884 TI - Spaces of social inclusion and belonging for people with intellectual disabilities. AB - People with intellectual disabilities (IDs) have been defined as 'socially excluded' and policies of 'social inclusion' invoked to counter this through a focus on paid work and independent living. For many people with IDs this is either not desired or not possible, and as a result many have sought out alternative spaces and activities of inclusion. The paper provides a critique of social exclusion and inclusion, and then goes onto examine (using two case studies) the ways in which people with IDs develop feelings of attachment and belonging within artistic spaces. The paper concludes that not only do these spaces provide mostly positive outcomes for individual people, but also have a potential role in 'reinscribing' the social and cultural understanding of people with IDs. PMID- 20586885 TI - Who's the expert? Rethinking authority in the face of intellectual disability. AB - This article poses the question, 'Who is the expert?' in relation to people with intellectual disabilities. It begins with an exploration of what it means to assert moral authority in relation to people with IDs, and makes the argument that 'experts' who draw moral boundaries, define conceptions of the 'good' and quality of life for people must consider how to occupy this position responsibly. It then considers a second form of authority--epistemic authority--and explores the moral responsibility that accompanies the practice of putting forth knowledge claims about ID. This involves acknowledging three potential problems: distancing, oppression and dehumanization. The article concludes with questions that point towards greater interdisciplinary dialogue regarding authority, responsibility and the role of the expert. PMID- 20586886 TI - From autonomy to relationships: productive engagement with uncertainty. AB - This paper argues that we are at a point of change in ID services, that new ideas and different frames of reference are required to take services forward in the 21st century. We describe how contemporary thinking in architecture, philosophy and organisational theory can assist in generating service principles for specialist services that allow us to better address the continuing isolation that is the experience of many people with ID, and the moral judgements that can limit service possibilities. We do not seek to offer a rigid blueprint for any particular service but one that allows for agency from its participants and relationships between them. PMID- 20586887 TI - Emerging themes. PMID- 20586888 TI - TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway. AB - Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response. PMID- 20586889 TI - Enhanced production of melatonin by ectopic overexpression of human serotonin N acetyltransferase plays a role in cold resistance in transgenic rice seedlings. AB - Serotonin N-acetyltransferase (SNA), a rate-limiting enzyme in melatonin biosynthesis in vertebrates, is responsible for the production of N acetylserotonin; this molecule is then converted to melatonin by hydroxyindole-O methyltransferase. We generated transgenic rice plants via expression of the human SNA gene under the constitutive ubiquitin promoter using Agrobacterium mediated gene transformation. We investigated the role of SNA in the biosynthesis of melatonin and the physiological role of melatonin in rice plants. The integration and expression of the transgene were confirmed in T(1) transgenic rice seedlings by Southern, Northern, and RT-PCR analyses. High SNA-specific enzyme activities were observed in the transgenic rice plants, whereas the wild type revealed a trace level of SNA enzyme activity. The functional expression of SNA protein was closely associated with the elevated synthesis of N acetylserotonin and melatonin in the transgenic rice plants. Experiments using both exogenous treatment of serotonin and senescent detached leaves, which contain a pool of serotonin, significantly enhanced melatonin biosynthesis, indicating that endogenous serotonin levels play a bottleneck role in the pathway of melatonin biosynthesis. Finally, the transgenic rice seedlings with high levels of melatonin showed elevated chlorophyll synthesis during cold stress, suggesting a role for melatonin in cold-stress resistance. PMID- 20586890 TI - Influence of melatonin on the order of phosphatidylcholine-based membranes. AB - The effect of melatonin was evaluated on three phosphatidylcholine-based membrane models. Changes in liposome dynamics were monitored by fluorescence, following the response of the probe merocyanine-540, as well as by differential scanning calorimetry (DSC). Langmuir monolayers were investigated using molecular area measurements, as well as by Brewster angle microscopy (BAM). Mica-supported bilayers were observed via atomic force microscopy (AFM). Fluorescence results demonstrating that melatonin increases the affinity between MC-540 and lipid molecules possibly because of an increase in the membrane fluidity in liposomes. DSC analyses showed that melatonin promoted a reduction in enthalpy in the lipid nonpolar chains. Melatonin also promoted an increase in the molecular area of Langmuir monolayers, as well as a decrease in membrane thickness. Consequently, melatonin appeared to induce re-ordering effects in liposome and Langmuir monolayers. AFM images of bilayers immobilized on mica suggested that melatonin induced a gel state predominance or a delay in the main phase transition. At experimental conditions, melatonin interacted actively with all membranes models tested and induced changes in their physico-chemical properties. The data presented here may contribute to the understanding of melatonin physiologic properties, as well as the development of therapeutic advanced systems, such as drug delivery systems and biosensors. PMID- 20586891 TI - Cardiology and Nephrology: time for a more integrated approach. Guest editorial. PMID- 20586892 TI - Cardiology and Nephrology: time for a more integrated approach. Editorial. PMID- 20586893 TI - Cardiology and Nephrology: time for a more integrated approach. Foreword. PMID- 20586894 TI - Clinical epidemiology of cardiovascular disease in chronic kidney disease. AB - The public health importance of chronic kidney disease (CKD) has only come to be appreciated in the last decade. While glomerular filtration rate (GFR) and urinary albumin creatinine levels are highly predictive of mortality, thresholds that may be useful for screening may be much closer to 'normal' than generally recognised. When optimising the balance between true negative and true positive mortality prediction, GFR from creatinine and GFR from cystatin C and albumin creatinine ratios all seem to perform similarly. Among the older population, mortality rates with creatinine-based GFR are lowest for those with levels between 60 and 90 ml/min/1.73 m(2), unlike with GFR from cystatin C, where mortality rates climb monotonically with declining GFR. Thus, the validity of creatinine-based GFR in older community-dwelling individuals is questionable. Nationally, representative data suggest management of modifiable cardiovascular risk factors in adults with CKD is far from optimal. This paper explores the possibility that robust associations between declining kidney function and cardiovascular outcomes could be caused by an unknown, confounding, shared-risk factors and extrapolates findings from renal transplant donor populations to support this hypothesis. PMID- 20586895 TI - Cardio-renal syndromes. AB - 'Cardio-Renal syndromes' (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy. PMID- 20586896 TI - Pathophysiological mechanisms contributing to renal dysfunction in chronic heart failure. AB - Renal dysfunction is extremely common in patients with chronic heart failure (CHF). Although the pathogenesis of reduced glomerular filtration rate (GFR) may differ between patients and even over time within an individual, the result is the same: reduced GFR is strongly related to increased mortality and morbidity. Potential explanations for the renal impairment include shared aetiological risk factors, such as atherosclerosis, hypertension, endothelial dysfunction and inflammation. Furthermore, a complex series of pathophysiological interactions exists between these two organ systems; an abnormality in one system will in general adversely impact on the other, resulting in a vicious cycle of disease progression. Improved understanding of the aetiology of reduced GFR in patients with CHF is fundamental to identifying appropriate therapies. Whilst reduced cardiac output and thereby renal perfusion is undoubtedly important, other factors, such as increased central venous pressure and anaemia may be amenable to therapeutic intervention. PMID- 20586897 TI - Lipids in chronic kidney disease. AB - Patients with chronic kidney disease (CKD) develop premature cardiovascular disease. In the general population (without CKD), there are strong associations between cholesterol fractions and the risk of coronary disease and weaker associations with stroke. Randomised trials in the general population demonstrate that lowering blood cholesterol (chiefly with a statin) reduces the risk of vascular events. Patients with CKD differ significantly from the general population. They have markedly disturbed lipid metabolism manifesting as elevated triglyceride concentrations, reduced HDL cholesterol concentrations and a preponderance of small, dense LDL particles that are potentially more atherogenic; the observed association between lipids and vascular disease is bizarre, and is confounded by co-morbidity; the nature of the vascular disease appears less strongly associated with classical atherosclerosis. Randomised trials are required to determine the relevance of blood lipids to the development of vascular disease in CKD patients, but the results of such studies have been inconclusive to date. CKD patients are at risk of end-stage renal disease. Lipids may be involved in the progression of renal disease. Modifying them may delay the progression of CKD. The current data are based on effects on markers of progression (e.g. proteinuria). The ongoing SHARP (Study of Heart and Renal Protection) trial should provide reliable information about the effects of statins on both vascular and renal risk. PMID- 20586898 TI - The diabetic CKD patient--a major cardiovascular challenge. AB - The diabetic patient with chronic kidney disease (CKD) is at very high risk of cardiovascular disease (CVD). Primary and secondary CVD prevention is of major importance and should be targeted at both traditional cardiovascular risk factors and risk factors specific for patients with CKD, such as albuminuria, anaemia and CKD--mineral and bone disorder. However, treatment goals have largely been derived from clinical trials including patients with no or only mild CKD and may not be generalizable to patients with advanced renal disease. Moreover, in patients on renal replacement therapy, the association between traditional CVD risk factors and the incidence of CVD may be reversed, and pharmaceutical interventions that are beneficial in the general population may be ineffective or even harmful in this high-risk population. Those involved in the delivery of care to patients with diabetes and CKD need to be aware of these issues and should adopt an individualised approach to treatment. PMID- 20586899 TI - Influence of dialysis therapies in the development of cardiac disease in CKD. AB - It is well recognised that dialysis patients suffer excess morbidity and mortality and that this is mainly due to cardiac failure and sudden cardiac death rather than conventional risk factors. Dialysis patients are primed by a number of structural, functional and microcirculatory abnormalities to experience demand myocardial ischaemia. We have shown that haemodialysis induces repetitive myocardial ischaemia in the majority of patients. In this way, haemodialysis itself may contribute to the development of heart failure and the risk of sudden death. There is recent appreciation that peritoneal dialysis is also capable of exerting short-term effects on cardiovascular performance through mechanisms both mutual and exclusive to haemodialysis. The aim of this paper is to give an appreciation of the possibility that modification of the dialysis procedure is capable of improving treatment tolerability and has the potential to reduce the excessive rates of cardiovascular morbidity and mortality. PMID- 20586900 TI - Ventricular arrhythmias and sudden death in patients with chronic kidney disease. AB - One in four dialysis patients will die suddenly. Most do not fall into the high risk categories that are associated with sudden death in the general population. The cause of sudden death in the dialysis population is unknown. It may be related to factors associated with chronic kidney disease (CKD) itself, for example, inflammation, vascular stiffness, left ventricular hypertrophy, coronary artery disease, electrolyte/fluid abnormalities or autonomic dysfunction. Studies of patients with implantable cardioverter defibrillators have shown that patients with CKD are more likely to use their devices for ventricular arrhythmias but in spite of this still have a high associated mortality. Until a comprehensive risk stratification strategy is understood, minimising risk by good control of basic parameters such as fluid balance, electrolytes and blood pressure, along with careful assessment of all patients for evidence of coronary artery disease and heart failure is the mainstay of management of the CKD patient. PMID- 20586901 TI - The association of chronic kidney disease-mineral bone disorder and cardiovascular risk. AB - Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as 'renal osteodystrophy' or 'renal bone disease'. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered. PMID- 20586902 TI - Screening for cardiovascular disease in patients with advanced chronic kidney disease. AB - Cardiovascular disease remains the major cause of mortality and morbidity in patients with advanced chronic kidney disease (CKD) and after renal transplantation. The mechanisms for cardiotoxicity are multiple. Identifying high risk patients remains a challenge. Given, the poor long-term outcome of dialysis patients who do not receive renal transplantation and the lower supply of donor kidneys relative to demand, optimal selection of renal transplantation candidates is crucial. This requires a clear understanding of the validity of cardiac tests in this patient group. This paper explores the strengths and weaknesses of currently available diagnostic tools in patients with advanced CKD. Echocardiography is very useful for the detection of cardiomyopathy and prognosis. Stress echocardiography, myocardial perfusion imaging and coronary angiography are the best tools for the assessment of coronary artery disease. All predict outcome. No single gold standard investigation exists. At present, there is not an optimal technique for predicting sudden cardiac death in this patient group. Ultimately, the choice of cardiac test will always be determined by patient preference, local expertise and availability. PMID- 20586903 TI - Practical management of diet and lifestyle interventions for people with diabetes or cardiovascular disease. AB - Increased collaboration between the vascular specialities is clearly leading to increased understanding of the interrelationships between the different disease states and how each impacts and influences the other. This advantage will be reflected in improved patient care if the practical outputs of this growing knowledge are carefully implemented at service level. This article outlines how the aspects of diet and lifestyle associated with vascular-related disease complement, contrast and in some cases contradict each other. It gives information and guidelines as to how the expertise of dietitians working in the different specialist areas might usefully be shared to be of maximum advantage to all patients. PMID- 20586904 TI - Anaemia management in cardio renal disease. AB - Anaemia is common in congestive heart failure (CHF) and is associated with increased mortality, morbidity and progressive renal failure. The common causes of the anaemia are the associated renal failure and excessive cytokine production, both of which can cause depression of the erythropoietin (EPO) production in the kidney and depression of EPO response in bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. Attempts to control this anaemia will have to consider the use of both erythropoiesis stimulating agents (ESA) as well as oral and, probably more importantly, intravenous (IV) iron. Studies of anaemia in CHF with ESA and oral or IV iron and even with IV iron alone have shown a positive effect on hospitalisation, fatigue and shortness of breath, cardiac and renal function, quality-of-life, exercise capacity and reduced beta natriuretic peptide and have not demonstrated an increase in cardiovascular damage related to therapy. Although some studies and meta-analyses have revealed improvement in these parameters others have not. Adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are needed and are currently being carried out. PMID- 20586905 TI - The importance of renin-angiotensin blockade in patients with cardio-renal disease. AB - The existence of the renin-angiotensin-aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin-angiotensin-aldosterone system will continue to be a key area of interest for many years to come. PMID- 20586906 TI - Coronary revascularisation in chronic kidney disease. Part 1: stable coronary artery disease. AB - Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease, myocardial infarction and cardiovascular death. Detection and treatment of coronary artery disease in CKD patients has been hampered by the limitations of screening tests, the lack of direct evidence for therapeutic interventions in this specific population, and concerns about therapy-related adverse effects. However, these patients potentially have much to gain from conventional strategies used in the general population. This review summarises the current evidence regarding the treatment of coronary artery disease in patients with CKD, with the focus on coronary revascularisation by percutaneous coronary intervention or coronary artery bypass grafting. PMID- 20586907 TI - Coronary revascularisation in chronic kidney disease. Part II: acute coronary syndromes. AB - Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease, myocardial infarction and cardiovascular death. Management of patients with CKD presenting with acute coronary syndromes is more complex than in the general population, due to greater diagnostic uncertainty and the lack of direct evidence for therapeutic interventions in this specific population, coupled with concerns about therapy-related adverse effects. However, these patients potentially have much to gain from conventional revascularisation strategies used in the general population. This review summarises the current evidence regarding the treatment of patients with CKD presenting with acute coronary syndromes, in particular with respect to coronary revascularisation strategies. PMID- 20586908 TI - Heart failure and chronic kidney disease: an integrated care approach. AB - Renal impairment may be evident at any stage of heart failure (CHF). Up to 30% of patients with heart failure have abnormal renal function. Chronic kidney disease (CKD) can be a complication of heart failure and chronic heart disease can be a consequence of CKD. Members of the multidisciplinary team, such as nurses, dieticians and physiotherapists should be encouraged to maximise their knowledge and skills across disease areas to influence and improve outcomes of those with CKD and CHF. In particular management of fluid balance, blood pressure control/monitoring, discussion of blood results and reduction of cardiovascular risk factors. Close monitoring and effective management of modifiable cardiac risk factors, such as diabetes and hypertension can reduce onset and slow progression of CKD. This can be done by applying the key principles of good practice, such as communication between healthcare professionals, patient education and empowerment alongside early identification and management of symptoms of CKD and CHF. PMID- 20586909 TI - Cardiovascular disease in renal transplant recipients. AB - Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature. PMID- 20586910 TI - Atherosclerotic renovascular disease and the heart. AB - The detrimental link between cardiac and renal pathophysiology in atherosclerotic renovascular disease (ARVD) is well described. Patients with ARVD usually have significant atherosclerotic disease in other vascular beds including the coronary circulation, and structural and functional cardiac changes are highly prevalent. This excess cardiovascular burden probably contributes to the increased cardiac morbidity and mortality seen in these patients. In this review we describe the associations of cardiovascular disease and ARVD and treatment thereof. The clinical debate of which patients are offered any additional advantage by revascularisation over medications alone remains to be answered. The close link between cardiac and renal pathophysiology in ARVD raises the possibility that renal revascularisation might confer a benefit to cardiac morphology and function. This is the subject of ongoing randomised controlled trials. PMID- 20586911 TI - Cardiac rehabilitation for patients with chronic kidney disease. AB - Cardiac Rehabilitation programmes are an integrated part of the total care of the patient and are delivered by a multidisciplinary team. Cardiac Rehabilitation is usually organised in four phases and has shown to reduce the morbidly and mortality associated with cardiac disease. Chronic Kidney Disease patients who are at risk of, or already have, Cardiovascular Disease should be monitored, educated and managed through close working relationships between the renal and cardiac multidisciplinary teams. One mechanism by which this may be achieved is through the use of cardiac rehabilitation programmes. PMID- 20586912 TI - Weight loss in obese patients with chronic kidney disease: who and how? AB - Obesity has adverse consequences in the general population. In patients with chronic kidney disease (CKD), it is associated with increased inflammation, insulin resistance, hypertension and dyslipidaemia, which are important risk factors for CKD progression and death. In adults with CKD stages 1-4, weight loss should be encouraged, it reduces proteinuria and glomerular hyperfiltration, which are frequent in obese patients. Proposals for modifications of lifestyle, physical activity and calorie restriction are the first measures. Pharmacological treatments are generally unsafe in these patients, except orlistat, but that has modest efficacy. Bariatric surgery may be the only option in severe obesity, if all other measures fail. For obese patients on dialysis treatment, who are eligible for kidney transplantation, weight loss is mandatory to prevent obesity related surgical complications and improve patient and graft survival after transplantation. Interventions should place an emphasis on exercise to increase muscle mass, and calorie but not protein restriction. Bariatric surgery should be carried out by experienced surgeons due to the high risk of complications. For obese patients who are not considered transplant candidates the benefits of weight loss remain uncertain. PMID- 20586913 TI - Abstracts from the Meetings of Asia Pacific Society for Sexual Medicine (APSSM) and Latin American Society for Sexual Medicine (SLAMS). PMID- 20586914 TI - Abstracts from the 9th Annual Meeting of the International Society for the Study of Women's Sexual Health (ISSWSH). St. Petersburg, Florida, USA. February 18-21 2010. PMID- 20586916 TI - Iliac vein thrombosis: feasibility assessment of randomized controlled trials of endovascular pharmacomechanical thrombolysis. AB - BACKGROUND: Optimal treatment for iliac vein thrombosis has not been established by randomized clinical trials largely owing to difficulty in patient recruitment. To assess the feasibility of a prospective randomized trial of thrombolysis and stenting, we determined the incidence of iliac vein thrombosis and randomization eligibility based on criteria for two ongoing trials. METHODS: All patients with incident leg deep vein thrombosis during the calendar year 2005 seen at the Mayo Clinic were identified to determine the frequency of iliac vein involvement and the number undergoing endovascular therapies. Each patient was assessed for eligibility for potential randomization into a theoretic trial of thrombolytic therapy. RESULTS: Ninety-five (of 394) patients had iliac vein involvement. Of these, only nine patients would have been suitable for randomization. Of the remaining 86 patients, prolonged symptom duration (n = 28), active cancer (n = 24) and advanced age (n = 19) were the most common exclusion criteria. Of 31 patients who had intervention, 75% had at least one contraindication for randomization. CONCLUSIONS: Despite a philosophy of aggressive treatment for iliac vein thrombosis at this institution, the number of cases that could potentially be randomized into a clinical trial is relatively small. Trial design may require either multicenter cooperation or exclusion criteria revision for adequate recruitment. PMID- 20586917 TI - Predominance of left-sided deep vein thrombosis and body weight. PMID- 20586915 TI - A G(i) -independent mechanism mediating Akt phosphorylation in platelets. AB - BACKGROUND: The serine-threonine kinase Akt plays an important role in regulating platelet activation. Stimulation of platelets with various agonists results in Akt activation as indicated by Akt phosphorylation. However, the mechanisms of Akt phosphorylation in platelets are not completely understood. OBJECTIVES AND METHODS: We used P2Y1 knockout mice to address the role of P2Y12 in Akt phosphorylation in response to thrombin receptors in platelets. RESULTS: Thrombin or the PAR4 thrombin receptor peptide AYPGKF at high concentrations stimulated substantial phosphorylation of Akt residues Thr308 and Ser473 in P2Y12-deficient platelets. AYPGKF-induced Akt phosphorylation is enhanced by expression of recombinant human PAR4 cDNA in Chinese hamster ovary (CHO) cells. P2Y12 independent Akt phosphorylation was not inhibited by integrin inhibitor peptide RGDS or integrin beta3 deficiency. Akt phosphorylation induced by thrombin or AYPGKF in P2Y12-deficient platelets was inhibited by the calcium chelator dimethyl-BAPTA, the Src family kinase inhibitor PP2, and PI3K inhibitors, respectively. CONCLUSIONS: Our results reveal a novel P2Y12-independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors. PMID- 20586918 TI - Proinflammatory and hypofibrinolytic phenotype in healthy first-degree relatives of patients with Type 2 diabetes. PMID- 20586919 TI - A critical appraisal of bleeding events reported in venous thromboembolism prevention trials of patients undergoing hip and knee arthroplasty. AB - BACKGROUND: Anticoagulants are effective for the prevention of venous thromboembolism (VTE) but cause bleeding. Interpretation of the risks and benefits of new anticoagulant regimens for VTE prevention is complicated by a lack of standardized definitions and reporting of bleeding. We reviewed the reporting of bleeding in randomized controlled trials of new anticoagulants compared with standard doses of enoxaparin in hip and knee arthroplasty, and examined the possible impact of differences in the definition of major bleeding on interpretation of the trial results. METHODS: Electronic searches identified 16 phase III trials published between 2001 and 2010 involving 41,265 patients comparing one of five new anticoagulants with a common comparator, enoxaparin. RESULTS: Major bleeding rates in patients treated with enoxaparin ranged from 0.1% to 3.1% in hip arthroplasty trials and from 0.2% to 1.4% in knee arthroplasty trials. In studies that excluded surgical-site bleeding from the definition, major bleeding rates were about 10-fold lower than in those which included surgical-site bleeding. Within the individual trials, the choice of bleeding definition and the methods of assessment of bleeding influenced the conclusions regarding the risk of bleeding with new anticoagulant regimens relative to enoxaparin. Eight of the 16 studies demonstrated a >= 40% relative risk differences in major bleeding between treatment groups but the difference was statistically significant in only two of these trials. CONCLUSION: Randomized VTE prevention trials report markedly different rates of major bleeding despite similar patient populations and doses and durations of anticoagulant prophylaxis and were underpowered to detect modest differences in patient-important bleeding events. Standardization of bleeding definitions and reporting seems desirable. PMID- 20586920 TI - Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study. AB - BACKGROUND: Enoxaparin has been extensively studied in adults on its safety and efficacy during prevention of symptomatic thromboembolism when acute anticoagulation or secondary prevention is required as a result of venous thrombosis or stroke. In children, it is still used off-label and little is known about the pharmacokinetics in children. OBJECTIVES: The aim of the present study was to evaluate whether a once- or twice-daily dosing regimen would be feasible in children to achieve appropriate plasma levels of enoxaparin. PATIENTS/METHODS: A population pharmacokinetic model was developed using anti-factor (F)Xa activity data from 126 children (median age: 5.9 years) receiving enoxaparin either as a once- or twice-daily dosing regimen. RESULTS: A two-compartment model was adequate for describing the enoxaparin kinetics. Body weight proved to be the most predictive covariate for clearance and central volume of distribution: clearance 15 mL h-1 kg-1, central volume of distribution 169 mL kg-1, intercompartmental clearance 58 mL h-1, peripheral volume of distribution 10 L and absorption rate 0.414 h-1. Interindividual variability was found to be 54% for clearance and 42% for volume of distribution. CONCLUSION: The model is capable of describing all age groups and dosing levels of our population and predicts 12 h and 24 h enoxaparin activities sufficiently. According to our results, a once-daily enoxaparin dosing regimen with frequent monitoring is feasible. In 53.2% of the patients the median 24 h trough level was above the desired range of 0.1 IU mL-1 anti-FXa activity for prophylaxis therapy. PMID- 20586921 TI - Model thrombi formed under flow reveal the role of factor XIII-mediated cross linking in resistance to fibrinolysis. AB - BACKGROUND: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. METHODS: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. RESULTS: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. CONCLUSIONS: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve gamma-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis. PMID- 20586922 TI - Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. AB - Arthropathy is a frequent and serious complication of repeated joint bleeding in patients with hemophilia, resulting in pain, deformity, and disability. Although the pathogenesis of hemophilic arthropathy has not been fully elucidated, it appears to have similarities with the degenerative joint damage that occurs in osteoarthritis and the inflammatory processes associated with rheumatoid arthritis. This article reviews the potential actions of various blood constituents on joint components that culminate in the development of hemophilic arthropathy. PMID- 20586923 TI - Randomized, double-blind comparison of effects of abiciximab bolus only vs. on label regimen on ex vivo inhibition of platelet aggregation in responders to clopidogrel undergoing coronary stenting. AB - BACKGROUND: On top of aspirin, an abciximab bolus-only regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time. OBJECTIVES: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry. PATIENTS/METHODS: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600-mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as >= 50% 5 MUmol L-1 ADP-induced maximum platelet aggregation. RESULTS: In clopidogrel responders (n = 68), IPA after 20 MUmol L-1 ADP at 4 h was 89% +/- 13% in the bolus-only arm vs. 92% +/- 14% in the bolus + infusion arm (P = 0.011 for non-inferiority). IPA after 5 or 20 MUmol L-1 ADP and 5 or 15 MUmol L-1 TRAP and the proportion of patients showing >= 80% IPA did not differ at any time point, irrespective of clopidogrel responsiveness status. Thirty-day outcomes were similar, whereas hemoglobin (0.91 +/- 0.8 vs. 0.5 +/- 0.7 g dL-1 ; P = 0.01) and platelet count mean drop (41.7 +/- 57 vs. 18.6 +/- 34 109 L-1; P = 0.042) were significantly reduced in the bolus-only arm. CONCLUSIONS: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs. PMID- 20586924 TI - Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotype. AB - BACKGROUND: von Willebrand disease (VWD) type Normandy (VWD 2N) is caused by mutations at the factor (F)VIII-binding site of von Willebrand factor (VWF), located in the D'and D3 domains on the N-terminus of mature VWF. The R854Q mutation is the most frequent cause of this phenotype. OBJECTIVES: We report the characterization of a homozygous VWD 2N mutation, R854W, detected in a patient with a severe VWD phenotype. METHODS: The plasma VWF phenotype was studied, transient expression of recombinant mutant full-length VWF in 293 EBNA cells was performed, and the results were compared with those obtained with wild-type (WT) VWF. Furthermore, expression was also examined in HEK293 cells, which form Weibel Palade body-like granules when transfected with WT VWF. RESULTS: The multimer analysis of plasma VWF showed the lack of the typical triplet structure, with the presence of the central band only, and a relative decrease in the high molecular mass multimers. Homozygous expression of recombinant R854W VWF resulted in normal amounts of cellular VWF, but with a severe reduction in secretion into the medium. Severe reductions in FVIII binding to R854W VWF, glycoprotein Ib binding activity and collagen binding of secreted W854 VWF was observed, and reproduced the phenotypic parameters of plasma VWF. In HEK293 cells, homozygous R854W VWF failed to form Weibel-Palade body-like granules. CONCLUSIONS: Our results demonstrate that a homozygous R854W mutation in the D' domain of VWF induces impaired secretion and activity of the protein, thereby explaining the severe phenotype of the patient. PMID- 20586925 TI - Anagrelide represses GATA-1 and FOG-1 expression without interfering with thrombopoietin receptor signal transduction. AB - BACKGROUND: Anagrelide is a selective inhibitor of megakaryocytopoiesis used to treat thrombocytosis in patients with chronic myeloproliferative disorders. The effectiveness of anagrelide in lowering platelet counts is firmly established, but its primary mechanism of action remains elusive. OBJECTIVES AND METHODS: Here, we have evaluated whether anagrelide interferes with the major signal transduction cascades stimulated by thrombopoietin in the hematopoietic cell line UT-7/mpl and in cultured CD34(+) -derived human hematopoietic cells. In addition, we have used quantitative mRNA expression analysis to assess whether the drug affects the levels of known transcription factors that control megakaryocytopoiesis. RESULTS: In UT-7/mpl cells, anagrelide (1MUm) did not interfere with MPL-mediated signaling as monitored by its lack of effect on JAK2 phosphorylation. Similarly, the drug did not affect the phosphorylation of STAT3, ERK1/2 or AKT in either UT-7/mpl cells or primary hematopoietic cells. In contrast, during thrombopoietin-induced megakaryocytic differentiation of normal hematopoietic cultures, anagrelide (0.3MUm) reduced the rise in the mRNA levels of the transcription factors GATA-1 and FOG-1 as well as those of the downstream genes encoding FLI-1, NF-E2, glycoprotein IIb and MPL. However, the drug showed no effect on GATA-2 or RUNX-1 mRNA expression. Furthermore, anagrelide did not diminish the rise in GATA-1 and FOG-1 expression during erythropoietin-stimulated erythroid differentiation. Cilostamide, an exclusive and equipotent phosphodiesterase III (PDEIII) inhibitor, did not alter the expression of these genes. CONCLUSIONS: Anagrelide suppresses megakaryocytopoiesis by reducing the expression levels of GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific and does not involve inhibition of MPL-mediated early signal transduction events. PMID- 20586927 TI - Achieving ultimate control of hepatitis B infection in China: progress and challenges. PMID- 20586928 TI - Epidemiology and prevention of hepatitis B virus infection in China. AB - The concept of a hepatitis B vaccine was first introduced into China in 1978. China has been one of the first two developing countries to enact the universal hepatitis B vaccination programme for newborn babies in 1992, and has made tremendous achievements in the control of hepatitis B virus (HBV) infection since then. China now has both low and high endemic regions regarding HBV prevalence co existing. Although China's drive to stop HBV spread has resulted in changes in HBV epidemic patterns, for the eventual elimination HBV infection in China, it is important to understand the current status of its epidemiology and the aspects of HBV transmission in different regions. More efforts are needed to improve and develop strategies for the control of HBV infection in China, particularly after implementing the policy of universal HBV immunization for all newborns. PMID- 20586929 TI - Management of chronic hepatitis B: experience from China. AB - Chronic hepatitis B infection is a significant health problem throughout the world, and particularly in China. It is estimated that more than half a million Chinese people die annually from end-stage hepatitis B complications, which is associated with huge healthcare costs and a heavy socioeconomic burden. In China, the implementation of a hepatitis B vaccination programme has come into effect, and there has been a one-third decrease of the hepatitis B virus (HBV) carrier population since 1992. This great achievement changes China from a highly endemic area for HBV infection to an intermediate one. The predominant HBV genotypes in China are B and C, which might predispose patients to a poor antiviral response. Patients and physicians from China have been actively involved in the global research into and development of new antiviral agents. Patients have been recruited for global and domestic clinical trials on antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine and two pegylated interferon-alpha. In the future, more important data, focussing on optimization of the efficacy of antiviral agents, will be released from China, based on the newly launched National Eleven Five Plan Project on Hepatitis Research. Both economic development and healthcare system reform, including a new reimbursement policy, will make antiviral agents more accessible to Chinese patients. Ultimately, this will allow physicians greater opportunities to follow international and Chinese treatment recommendations. PMID- 20586930 TI - Serum peptide profiles during progression of chronic hepatitis B virus infection to liver failure. AB - Chronic hepatitis B virus (HBV)-infected patients with liver failure have a poor prognosis, and no satisfactory biomarkers are available for diagnosis before the end-stage. We explored serum peptide profiling for diagnosis and prediction of progression to liver failure in HBV-infected patients. Serum samples (164) from healthy subjects (n = 20), or subjects with chronic hepatitis B without cirrhosis and liver failure [chronic hepatitis B subjects without cirrhosis and liver failure (CHB); n = 33], with compensated liver cirrhosis (compensated liver cirrhosis (LC); n = 35), with acute-on-chronic liver failure [acute-on-chronic liver failure (ACLF); n = 38] or with chronic liver failure [chronic liver failure (CLF), n = 38] were applied to ClinProt magnetic beads, and bound peptides/proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Our classification diagnostic models of liver disease were generated based on the Genetic Algorithm (GA) and Quick Classifier Algorithm (QC). Differentially expressed peptides were found among all test groups, with patterns of difference that readily distinguished between healthy and various HBV-associated liver disease samples. The model generated seven characteristic peptide peaks at 4053 m/z, 3506 m/z, 4963 m/z, 9289 m/z, 2628 m/z, 3193 m/z and 6432 m/z, giving overall predictive capability of 54.27%. Two-way comparisons of LC, ACLF or CLF vs CHB had predictive capabilities of 79.8%, 91.41% and 97.99%, respectively. Comparisons of ACLF or CLF vs LC were predictive at 87.72% and 82.18%, respectively and ACLF vs CLF was predictive at 75.05%. These classification diagnostic models generated by different peptide peaks were further validated in blinded tests with 67-100% accuracy. Serum peptide patterns vary during progression of chronic HBV infection to liver failure and may be used to distinguish different stages of the disease. PMID- 20586931 TI - Telbivudine preserves T-helper 1 cytokine production and downregulates programmed death ligand 1 in a mouse model of viral hepatitis. AB - Telbivudine is an orally bioavailable L-nucleoside with potent and specific anti hepatitis B virus activity. The higher rate of hepatitis B e antigen (HBeAg) seroconversion during telbivudine treatment than other potent anti-HBV agents suggests a potential immunomodulatory effect. We sought to determine the effects of telbivudine on the immune system, particularly on cytokine production and T cell response, using an animal model with mouse hepatitis virus strain 3 (MHV-3) induced hepatitis. The effects of telbivudine on virus replication and cytokine production were investigated in vitro using MHV-3-infected macrophages, and the effects on T-cell response were investigated in vivo in an MHV-3-induced viral hepatitis model. Telbivudine had no effect on MHV-3 replication in macrophages. However, the production of tumour necrosis factor-alpha and interleukin-12 was increased significantly in MHV-3-induced macrophages treated with telbivudine. In vivo survival was enhanced in telbivudine-treated mice, with marked normalization in clinical conditions and histological lesions. Serum levels of interferon-gamma were elevated significantly after telbivudine treatment in MHV-3-infected C3H mice. In contrast, serum interleukin-4 levels were decreased significantly. Furthermore, telbivudine treatment enhanced the ability of T cells to undergo proliferation and secrete cytokines but did not affect cytotoxicity of infected hepatocytes. Of note, we found that telbivudine treatment suppressed programmed death ligand 1 expression on T cells. The results demonstrate the immunomodulatory properties of telbivudine, independent of its antiviral activity, in a mouse model of MHV-3-induced hepatitis. PMID- 20586933 TI - Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase. AB - Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (<= 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change. PMID- 20586932 TI - Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses. AB - Chronic hepatitis B (CHB) virus hepatitis B virus (HBV) infection is the key cause of hepatocellular carcinoma (HCC) in Asians. Recent studies have shown that levels of CD4(+)CD25(+) regulatory T cells (Tregs) were increased and were linked to an impaired immune response in patients with CHB. Evaluating whether Tregs are involved in the progression of CHB to HCC will provide insight into the immunopathogenesis of HCC. In the present study, we showed that circulating and liver-residing Tregs increased in CHB (n = 15) and HCC (n = 49) patients, particularly in the peripheral blood of HCC patients with HBV infection (n = 29). The increased Tregs in CHB patients suppressed the specific immune response induced by not only HBV antigen, but also by HCC tumour antigen. When peripheral blood mononuclear cells (PBMC) were co-cultured with human hepatoma cell lines that are stably transfected with HBV (HepG2.2.15), CD4(+)CD25(+) Treg populations increased and upregulated the expression of forkhead box P3 transcriptional regulator (FoxP3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor (TNF) receptor family gene (GITR). In contrast, PBMCs co-cultured with HepG2 cells (the parental cell line of HepG2.2.15) did not. CD4(+)CD25(+) Tregs isolated from PBMCs that were co cultured with HepG2.2.15 cells also had a greater suppressive ability with respect to the tumour antigen-specific immune response induced by NY-ESO-1 or MAGE-A3 compared with CD4(+)CD25(+) Tregs isolated from PBMCs co-cultured with HepG2 cells. The results offer evidence that the expansion of CD4(+)CD25(+) Tregs and the enhancement of the suppressor function of CD4(+)CD25(+) Tregs induced by HBV infection-related factors could suppress the anti-tumour immune response to HCC tumour antigen and inhibit tumour immuno-surveillance against HCC, which may be involved in the immunopathogenesis from CHB to HCC. PMID- 20586934 TI - Virological, serological and biochemical outcomes through 3 years of entecavir treatment in nucleoside-naive Chinese chronic hepatitis B patients. AB - Hepatitis B virus (HBV) infection has a high prevalence in China. Entecavir has shown superior efficacy over lamivudine in Chinese nucleoside-naive chronic hepatitis B (CHB) patients over 48 weeks, with continued clinical benefit to 96 weeks. The present study evaluates the long-term efficacy of entecavir in Chinese CHB patients who continued entecavir treatment for 144 weeks. Patients receiving either entecavir 0.5 mg/day (n = 258) or lamivudine 100 mg/day (n = 261) entered the initial 96-week randomized, double-blind, controlled efficacy study. Patients who did not achieve a consolidated response [HBV DNA <0.7 MEq/mL; alanine aminotransferase (ALT) <1.25 x upper limit of normal; and if hepatitis B e antigen (HBeAg) positive at baseline, loss of HBeAg for >= 24 weeks] or who experienced viral breakthrough or relapse entered a 48-week entecavir rollover study. A total of 160 patients received continuous entecavir for 144 weeks; of these, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, 20% reported HBeAg loss and 8% experienced HBeAg seroconversion. The cumulative rates of HBeAg loss and seroconversion were 36% and 27% at Week 144, respectively. The development of resistance was low, with three patients up to Week 96 and an additional two patients in Weeks 96-144 showing evidence of associated genotypic mutations. Entecavir was well tolerated. Adverse event rates were similar to those in lamivudine-treated patients, but patients receiving entecavir experienced fewer ALT flares. This study demonstrates that entecavir provides durable, long-term suppression of HBV DNA and ALT normalization in Chinese CHB patients, and is associated with low rates of emerging resistance. The results are consistent with the findings using entecavir globally and in Japan. PMID- 20586935 TI - Virological response to antiviral therapy at week 12 indicates a great reduction of intrahepatic hepatitis B virus DNA and cccDNA in HBeAg-positive chronic hepatitis B patients. AB - Early virological response is considered to be a predictor for the outcome of anti-hepatitis B virus (HBV) therapy. To analyze its correlation to intrahepatic HBV DNA and covalently closed circular DNA (ccc)DNA, 71 hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B patients were recruited: 34 patients were treated with lamivudine; 13 with interferon-alpha2b; and 24 with sequential therapy of lamivudine-interferon-alpha2b for 48 weeks. Intrahepatic HBV DNA and cccDNA load were measured at the baseline and at Week 48. Fifty-seven patients had virological response at Week 12. Median decreases of serum HBV DNA in patients with or without virological response at Week 12 were 4.0 log(10) (max. 6.2, min. 2.2) and 1.1 log(10) (max. 2.1, min. 0) (Z = -5.766, P = 0.0000), respectively. At Week 48 they were 4.1 log(10) (max. 7.4, min. 1.0) and 2.3 log(10) (max. 7.5, min. 0.3) (Z = -2.760, P = 0.006), respectively. For intrahepatic HBV DNA load they were 1.3 log(10) (max. 4.3, min. -1.2) and 0.6 log(10) (max. 3.5, min. -0.8), respectively, and for HBV cccDNA load they were 1.1 log(10) (max. 4.8, min. -0.5) and 0.5 log(10) (max. 3.0, min. -0.8) (Z = 2.097, P = 0.036), respectively at Week 48. Step-wise logistic regression analysis indicated that the baseline intrahepatic HBV DNA load effected virological response at Week 12 [odds ratio (OR) 0.405; 95% confidence interval (CI) 0.174-0.944; P = 0.036] and HBeAg seroconversion at Week 48 (OR 0.292; 95% CI 0.131-0.649; P = 0.003). In conclusion, virological response at Week 12 indicated a great reduction of intrahepatic DNA and cccDNA load in HBeAg-positive CHB patients. The baseline intrahepatic HBV DNA load affected virological response at Week 12 and HBeAg seroconversion at Week 48. PMID- 20586936 TI - rtE218G, a novel hepatitis B virus mutation with resistance to adefovir dipivoxil in patients with chronic hepatitis B. AB - Antiviral therapy is a potentially successful approach for the treatment of patients with Hepatitis B virus (HBV) infection. One antiviral agent is the nucleoside analogue adefovir dipivoxil (ADV). Its efficiency is compromised by the emergence of drug-resistant HBV mutants. Although three major ADV-resistant mutations of HBV are known, rtA181T/V and rtN236T, HBV mutations associated with ADV resistance have not been fully identified. We analyzed DNA sequences that covered a 244 base pair region of the HBV polymerase gene from patients with clinical manifestations of ADV resistance. A novel pattern of amino acid substitutions in HBV polymerase was detected in 26 out of 86 patients. This mutant exhibited a substitution of glycine for glutamic acid at residue 218 (rtE218G). Transient transfection of the HBV replication-competent construct including the rtE218G mutation was performed in HepG2 cells in order to determine the relevance of this mutation to ADV resistance. Phenotypic analyses demonstrated that the rtE218G mutation could independently confer resistance to ADV in vitro, with a 50% inhibitory concentration (IC(50)) 5.5-fold higher than wild-type HBV. RtE218G-mutated HBV also showed a decreased replication capacity in vitro, equal to 87% of wild-type HBV. The present study showed that the rtE218G mutation may be a novel ADV-resistant mutation. Further work will focus on resistance surveillance and cross-resistance analyses, and the molecular mechanisms involved. PMID- 20586937 TI - Multiplex PCR assays for simultaneous detection and characterization of Vibrio vulnificus strains. AB - AIMS: Vibrio vulnificus is a major cause of seafood-related deaths in the United States. Several biomarkers, e.g. the virulence-correlated gene (vcg), 16S rRNA, and the capsular polysaccharide operon (CPS) have been used to differentiate virulent- from nonvirulent-type V. vulnificus strains. In this study, we combined the use of these biomarkers with a species-specific V. vulnificus cytolysin/haemolysin gene (vvhA) to develop two pairs of multiplex PCR assays that simultaneously detect and characterize V. vulnificus strains. METHODS AND RESULTS: The first multiplex PCR pair amplified four genes (vvhA, vcg, 16S rRNA, and CPS), with one for virulent-type and the other one for nonvirulent-type V. vulnificus strains, while the second pair targeted three of those genes excluding CPS. Primer concentration and annealing temperature were optimized for the four multiplex PCR assays. When testing ten V. vulnificus reference strains and 80 field oyster isolates, results from each multiplex PCR matched 100% with known strain characteristics for these target genes. CONCLUSIONS: The optimized multiplex PCR assays were capable of simultaneously detecting and characterizing V. vulnificus with high specificity and speed. SIGNIFICANCE AND IMPACT OF THE STUDY: Multiplex PCR assays designed in this study are valuable tools for microbial ecology and epidemiology studies. They may facilitate better control of V. vulnificus risks in oysters, thereby reducing the number of illnesses and deaths because of V. vulnificus in the long run. PMID- 20586938 TI - High-density polyethylene (HDPE)-degrading potential bacteria from marine ecosystem of Gulf of Mannar, India. AB - AIMS: Assessment of high-density polyethylene (HDPE)-degrading bacteria isolated from plastic waste dumpsites of Gulf of Mannar. METHODS AND RESULTS: Rationally, 15 bacteria (GMB1-GMB15) were isolated by enrichment technique. GMB5 and GMB7 were selected for further studies based on their efficiency to degrade the HDPE and identified as Arthrobacter sp. and Pseudomonas sp., respectively. Assessed weight loss of HDPE after 30 days of incubation was nearly 12% for Arthrobacter sp. and 15% for Pseudomonas sp. The bacterial adhesion to hydrocarbon (BATH) assay showed that the cell surface hydrophobicity of Pseudomonas sp. was higher than Arthrobacter sp. Both fluorescein diacetate hydrolysis and protein content of the biofilm were used to test the viability and protein density of the biomass. Acute peak elevation was observed between 2 and 5 days of inoculation for both bacteria. Fourier transform infrared (FT-IR) spectrum showed that keto carbonyl bond index (KCBI), Ester carbonyl bond index (ECBI) and Vinyl bond index (VBI) were increased indicating changes in functional group(s) and/or side chain modification confirming the biodegradation. CONCLUSION: The results pose us to suggest that both Pseudomonas sp. and Arthrobacter sp. were proven efficient to degrade HDPE, albeit the former was more efficacious, yet the ability of latter cannot be neglected. SIGNIFICANCE AND IMPACT OF THE STUDY: Recent alarm on ecological threats to marine system is dumping plastic waste in the marine ecosystem and coastal arena by anthropogenic activity. In maintenance phase of the plastic-derived polyethylene waste, the microbial degradation plays a major role; the information accomplished in this work will be the initiating point for the degradation of polyethylene by indigenous bacterial population in the marine ecosystem and provides a novel eco-friendly solution in eco-management. PMID- 20586939 TI - Growing initiative by the Asian Forum of CKD Initiative (AFCKDI): the report of International Advisory Council/Work Group Meeting. PMID- 20586940 TI - Epidemiology, impact and preventive care of chronic kidney disease in Taiwan. AB - Chronic kidney disease (CKD) has emerged as a global public health burden. Taiwan has the highest incidence and prevalence rates of end-stage renal disease (ESRD) in the world. In this review, the following key issues of CKD in Taiwan are addressed: epidemiological data, underlying diseases patterns, risk factors, public health concerns and a preventive project. Prevalence of CKD are reported to be 6.9% for CKD stage 3-5, 9.83% for clinically recognized CKD and 11.9% for CKD stage 1-5. However, overall awareness of CKD is low, 9.7% for CKD stage 1-3 and 3.5% for stage 1-5. Diabetes mellitus (43.2%), chronic glomerulonephritis (25.1%), hypertension (8.3%) and chronic interstitial nephritis (2.8%) are four major underlying renal diseases of ESRD. Older age, diabetes, hypertension, smoking, obesity, regular use of herbal medicine, family members (both relatives and spouses), chronic lead exposure and hepatitis C are associated with higher risk for CKD. Impact of CKD increases risk of all-cause mortality and cardiovascular diseases, especially in those with overt proteinuria and advanced CKD stages. These impacts lead to increased medical costs. The nationwide CKD Preventive Project with multidisciplinary care program has proved its effectiveness in decreasing dialysis incidence, mortality and medical costs. It is crucially significant from Taiwan experience on CKD survey and preliminary outcome of the preventive project. Provision of a more comprehensive public health strategy and better care plan for CKD should be achieved by future international collaborative efforts and research. PMID- 20586941 TI - Herbal medicines and chronic kidney disease. AB - Alternative and indigenous systems of medicine are popular amongst the poorer sections of society in the developing world. Their use in the developed world has also increased in recent times. The source and composition of these medicines vary in different parts of the world, but herbs and other botanicals are central to these systems. Largely outside the ambit of regulatory control, herbal remedies are prepared by quasi-trained herbalists and not tested for safety. Toxicity can occur when a herb with unknown toxicity is consumed, incorrect identification leads to substitution of an innocuous herb with a toxic one, preparations are contaminated with toxic non-herbal compounds or when a herb potentiates the nephrotoxic effect of a conventional therapy. Renal injury has been reported in association with several herbs. The best-known herb-induced chronic kidney disease (CKD) is aristolochic acid nephropathy. The condition is characterized by progressive interstitial nephritis, with a proportion of patients developing urothelial malignancies. The toxic compound is aristolochic acid (AA); AA-DNA adducts have been identified in the renal and urothelial tissues. Recent evidence suggests that AA also contributes to the development of Balkan endemic nephropathy. The role of herbs has been postulated in the development of CKD in other parts of the developing world, especially amongst the rural population. Public awareness and regulation of use of herbal medicines are required to eradicate this entity from the community. PMID- 20586942 TI - Low birthweight and chronic kidney disease. AB - Low birthweight reflects the congenital defects of organs, which is associated with chronic kidney disease through its direct influence on nephron number and function, also through related metabolic disease-induced kidney damage. We reviewed the current evidence regarding the role of low birthweight in the pathogenesis of chronic kidney disease. PMID- 20586943 TI - Immunoglobulin A nephropathy and chronic kidney disease. AB - Immunoglobulin (Ig)A nephropathy is one of the major causes of chronic kidney disease (CKD) in Japan. Despite statutory urinalysis of industrial workers and school children, Japan unfortunately still ranks among the countries with the highest CKD-5D prevalence in the world. Topics of this review are as follow: (i) early diagnosis and treatment; (ii) influence of the period from onset to medical intervention on renal prognosis; and (iii) epidemiology of IgA nephropathy patients in Japan. Some investigators have discussed the possibility of predicting the diagnosis and prognosis of this disease. We indicated that the frequency of various casts in urinary sediments and total numbers of each type of urinary cast should provide highly convincing data for prediction of the prognosis in IgA nephropathy patients prior to renal biopsy. Furthermore, early medical intervention (anti-platelet agents, anticoagulants, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, corticosteroids and/or tonsillectomy) may lead to better renal prognosis in patients with IgA nephropathy. In a nationwide survey on IgA nephropathy in Japan, predictive factors after 10 years were as follows: (i) male sex; (ii) under 30 years old; (iii) diastolic hypertension; (iv) heavy proteinuria; (v) mild haematuria; (vi) low serum albumin; and (vii) elevated serum creatinine and impaired renal pathology. It appears that substantial renal deterioration can be validly estimated using these predictive factors in patients with IgA nephropathy. In conclusion, early diagnosis, treatment and improvement of predictive factors for a long duration may lead to better renal prognosis in patients with IgA nephropathy. PMID- 20586944 TI - Renal outcomes in chronic kidney disease. AB - The prevalence of treated patients with end-stage renal disease (ESRD) has been increasing steadily in Japan. High ESRD prevalence could be explained by multiple factors such as better survival on dialysis therapy, luxury acceptance due to insurance system to cover dialysis therapy, and 'truly' high incidence and prevalence of chronic kidney disease (CKD). The growing elderly population may also contribute to this trend. The Japanese Society of Nephrology estimated the prevalence of CKD stage 3 as 10.4%, 7.6% within the range of 50-59 mL/min per 1.73 m(2) in a screened population. Strong predictors of treated ESRD shown by using community-based screening programs and an ESRD registry in Okinawa are dip stick-positive proteinuria and hypertension. Low glomerular filtration rate per se, which is often observed in the elderly population, is not a significant predictor of developing ESRD unless associated with proteinuria. CKD is common in Japan and is expected to increase, particularly in the elderly population. Benefits of proteinuria screening and automatic reporting of estimated glomerular filtration rate on the incidence of ESRD remain to be determined. PMID- 20586945 TI - Challenging chronic kidney disease: experience from chronic kidney disease prevention programs in Shanghai, Japan, Taiwan and Australia. AB - Chronic kidney disease (CKD) is now a global health problem. One important strategy to prevent and manage CKD is to offer a prevention program which could detect CKD early as well as raise awareness of the disease. In Shanghai, a community-based study demonstrated that the prevalence of CKD was high while awareness was low. The results from Shanghai urged the necessity of a screening and prevention program of CKD. In Japan, the urinalysis screening system was established to early diagnose and prevent CKD. Due to modification of lifestyle and prevalence of diabetes, urine dip-stick test for microalbuminuria might be necessary in adults while screening for proteinuria and haematuria are necessary for students and young adults. In Taiwan, two CKD programs - a CKD care program and diabetic share care program - were initiated. The cost-effectiveness study indicated that both programs could reduce end-stage renal disease (ESRD) burden in Taiwan because integrated pre-ESRD care was important for patients with CKD stage 4 and stage 5 while a diabetic shared care program was cost-effective to prevent nephropathy to patients with diabetic mellitus. In Australia, studies demonstrated that screening of high-risk individuals as well as promoting awareness were cost-effective to early detection of CKD. Furthermore, opportunistic screening with emphasis on early detection was effective in CKD prevention. The studies from those regions share experiences on early prevention and management of CKD. PMID- 20586946 TI - Chronic kidney disease awareness, screening and prevention: rationale for the design of a public education program. AB - Design principles for a chronic kidney disease (CKD) screening program start with the general population at increased risk of CKD. Simple risk factor analysis demonstrates diabetes, hypertension, cardiovascular disease and older age as significant associated conditions. More comprehensive risk factor analysis shows only diabetes and hypertension as risk factors in people aged less than 50-60 years, and that anyone aged older than 50-60 years is at risk. Assessment of the relationship between CKD stage and cardiovascular risk factors shows early stage CKD to be associated with poor blood pressure control, which should be addressed. Other risk factors should be more completely assessed to determine if participants and their physicians are adequately addressing factors amenable to treatment to reduce high adverse event rates, premature death and progression to end-stage renal disease (ESRD). Such assessment is needed to reduce the high burden of ESRD on national health-care systems, which can only be addressed by early screening and active treatment. PMID- 20586947 TI - Implication of global nephrology guidelines in Asia and 'Asian CKD Best Practice Guidelines'. AB - By establishing Kidney Diseases: Improving Global Outcome (KDIGO), nephrology has taken an important step towards developing global clinical practice guidelines (CPG). KDIGO published its first CPG on 'Hepatitis C in CKD' in 2008 and has since published two new CPG ('CKD-MBD' and 'Kidney Transplant Recipient') in 2009. A major obstacle to implement CPG is the lack of both high-quality evidence for regionally-specific areas of medicine and a lack of resources in many countries in our region. However, an endeavor by the Asian Forum of CKD Initiative (AFCKDI) may make it possible to overcome these obstacles. By developing regionally-specific CKD guidelines, the AFCKDI might identify relevant evidence gaps and by using specific expertise develop a standard of patient care appropriate to the Asia-Pacific region. This can be accomplished only by engaging a group of international experts who fully represent the Asia-Pacific area. PMID- 20586948 TI - Current status of estimated glomerular filtration rate (eGFR) equations for Asians and an approach to create a common eGFR equation. AB - CKD is now recognized as life-threatening disease and various countermeasures are implemented worldwide. The most important step to overcome CKD is early detection and evaluation. Equation for estimating GFR is the necessary tool for this step. This is also useful to follow-up CKD patients in routine clinical settings. Currently, most commonly used equation is original and re-expressed MDRD formula. For Asians, ethnic co-efficient is needed when applying these formulas. Ethnic co efficient is different among Asian countries. Recently, different original equations have been developed in several Asian countries. At the present time, it is not clear to develop a single common eGFR equation fit for Asians. There are several factors that affect GFR estimation. These include ethnicity, reference method to measure GFR, method of creatinine measurement and calibration. Towards the future, Asian collaborative study is necessary to validate and standardize eGFR equations. PMID- 20586949 TI - Salt and hypertension. AB - Current salt intake is too high. Current evidence documents that salt is crucial to the genesis of hypertension. PMID- 20586950 TI - Proteinuria versus albuminuria in chronic kidney disease. AB - Chronic kidney disease (CKD) is defined according to a decrease in the glomerular filtration rate and kidney damage such as proteinuria or albuminuria. Dip-stick proteinuria is only sensitive to albumin and correlates poorly with quantitative 24 h proteinuria, the most commonly used measure in renoprotective randomized controlled clinical trials (RCT). The amount of proteinuria correlates with the efficacy of angiotensin-converting enzyme inhibitors in non-diabetics in RCT. Random urine protein to creatinine ratio (PCR) or albumin to creatinine ratio (ACR) correlates with 24 h urinary excretion. Dip-stick proteinuria correlates poorly with ACR, while PCR correlates reasonably well with ACR. Because of a high analytical variability, efforts are in progress to standardize ACR (but not PCR) measurement. There have been no studies on the direct comparison between proteinuria and albuminuria in terms of utilities (biomarker, surrogate end-point and cost-effectiveness). In this regard, both proteinuria and albuminuria are good biomarkers for cardiovascular events, renal events or mortality. However, there are limitations in RCT regarding the validity of proteinuria or albuminuria as a surrogate end-point. In contrast, measuring proteinuria or albuminuria followed by treatment with angiotensin inhibitors is cost-effective for diabetics, hypertension and aging. CKD guidelines differ in their opinions regarding the choice between ACR and PCR. Based on the current evidence, ACR might be recommended for the diabetics and PCR for the non-diabetics. PMID- 20586951 TI - Optimal dose of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker for renoprotection. AB - Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) have become the cornerstone in the treatment of chronic kidney disease (CKD), as numerous lines of evidence have shown that these agents have a blood pressure lowing independent anti-proteinuric effect. However, despite the benefits of ACEI or ARB therapy, a substantial proportion of patients still experience renal morbidity and mortality. Considering the prognostic impact of proteinuria reduction, it is currently assumed that titration of ACEI or ARB for optimal anti-proteinuric effect would be a logical step towards improvement of renoprotection. Recent published studies, performed with higher than recommended doses of either ACEI or particularly ARB, suggest that the approach is associated with a further decrement in urinary protein excretion and probably improved renal outcome. Although most patients achieve their maximum benefit at standard doses, there is a residual group of patients who may do so at higher doses of renin-angiotensin system inhibitors. Because patients who would benefit from higher doses are not identifiable a priori, a titration process might be cogent in order to provide more robust anti-proteinuric benefit to such patients. PMID- 20586952 TI - Timely initiation of dialysis for chronic kidney disease: perspective from four Asian countries. AB - Recommendations about when to initiate dialysis for end-stage kidney failure have been made by a number of expert groups. These recommendations have led to changes in clinical practice, yet they are not based on high level evidence. In fact, most reported studies argue that dialysis should be started early rather than late, many are confounded and a number have reached the opposite conclusion. Probably more important than a prescribed level of renal function at which dialysis is initiated is the widespread adoption of a structured approach to pre dialysis care and the recognition of the importance of pre-dialysis patient education. One of the main determinants of optimal initiation of dialysis is the time of referral of the patient to a nephrologist or a renal unit. In particular, early referral of patients with chronic kidney disease allows a planned initiation of dialysis, using from the start permanent vascular or peritoneal dialysis access. PMID- 20586953 TI - Effect of luteinizing hormone and tumour necrosis factor-alpha on VEGF secretion by cultured porcine endometrial stromal cells. AB - To cope with rising demands for increased blood supply during pregnancy, the vasculature of the uterus undergoes several adaptive changes, including increased permeability, angiogenesis and vasodilatation. Although it is clear that vascular endothelial growth factor (VEGF) plays a paramount role in achieving these adaptations, little is known about regulation of VEGF expression in endometrium during pregnancy. Thus, we have investigated whether luteinizing hormone (LH) and tumour necrosis factor-alpha (TNFalpha) may affect VEGF secretion by stromal cells during early pregnancy in pigs. Real-time reverse transcription/polymerase chain reaction (RT/PCR) of VEGF120 and VEGF164 gene expression revealed significantly higher levels of VEGF164 mRNA in cultured stromal cells (p < 0.0001). The LH-stimulated secretion of VEGF was detected after 24 and 48 h of treatment when doses 50 and 100 ng/ml were used (p < 0.05 and p < 0.01, respectively). The TNFalpha-induced secretion of VEGF by stromal cells was detected only after 24-h treatment with the highest dose used in the experiment (50 ng/ml; p < 0.05). Although the influence of LH on VEGF secretion was more visible compared with TNFalpha, both factors may be considered as potential modulators of adaptive changes in uterine vasculature occurring during pregnancy in the pig. PMID- 20586954 TI - Comparison in effect of Heatsynch with heat detection aids and CIDR-Heatsynch in dairy heifers. AB - The objective of the present study was to determine whether oestrous detection with the help of oestrous detection aids during the Heatsynch without timed AI protocol is equally effective with the progesterone-combined protocol in dairy heifers. A total of 148 heifers were randomly assigned to one of the two groups. A group of heifers treated with Heatsynch with heat detection aids (n = 72) received GnRH on day 0, prostaglandin F(2alpha) (PGF(2alpha)) on day 7 and oestradiol benzoate (EB) on day 8, while in controlled internal drug release (CIDR)-Heatsynch group (n = 76), CIDR was included during a period from GnRH to PGF(2alpha). Heifers were checked for oestrus twice daily, i.e. from 09:00 to 10:00 hours and from 15:00 to 16:00 hours starting on day 2 for Heatsynch group and on day 8 in CIDR-Heatsynch group, and continued up to day 12. KAMAR heat mount detector (KAMAR Inc., Steamboat Springs, CO, USA) and ALL-WEATHER PAINTSTIK (LA-CO Industries Inc., Elk Grove Village, IL, USA) were used as heat detection aids. AI was conducted within 1 h after confirming oestrus in 72 heifers, while 19 animals were transferred with embryo 7 days after oestrus according to the request of the owners. Premature oestrus before PGF(2alpha) injection occurred in 18% of Heatsynch group. Of 13 heifers which showed premature oestrus, six were inseminated and two of them conceived. Oestrus detection rate within 12 days after initiation of the protocols did not differ between the two groups (94% vs 95%). There was no difference in the conception rate after first AI (including heifers that were inseminated before PGF(2alpha) injection) and embryo transfer between Heatsynch with heat detection aids and CIDR-Heatsynch groups (36% vs 44% and 70% vs 56%). It is concluded that the use of heat detection aids to monitor the occurrence of premature oestrus prior to PGF(2alpha) injection in Heatsynch protocol in dairy heifers was equally effective to the inclusion of CIDR. PMID- 20586955 TI - Retraction. The effect of intravaginal applied GnRH-agonist on the time of ovulation and subsequent reproductive performance of weaned multiparous sows. PMID- 20586956 TI - Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007-2009: systematic review. AB - OBJECTIVES: To estimate the proportion of all-cause adult patient attrition from antiretroviral therapy (ART) programs in service delivery settings in sub-Saharan Africa through 36 months on treatment. METHODS: We identified cohorts within Ovid Medline, ISI Web of Knowledge, Cochrane Database of Systematic Reviews and four conference abstract archives. We summarized retention rates from studies describing observational cohorts from sub-Saharan Africa reporting on adult HIV 1 infected patients initiating first-line three-drug ART. We estimated all-cause attrition rates for 6, 12, 18, 24, or 36 months after ART initiation including patients who died or were lost to follow-up (as defined by the author), but excluding transferred patients. RESULTS: We analysed 33 sources describing 39 cohorts and 226 307 patients. Patients were more likely to be female (median 65%) and had a median age at initiation of 37 (range 34-40). Median starting CD4 count was 109 cells/mm(3). Loss to follow-up was the most common cause of attrition (59%), followed by death (41%). Median attrition at 12, 24 and 36 months was 22.6% (range 7%-45%), 25% (range 11%-32%) and 29.5% (range 13%-36.1%) respectively. After pooling data in a random-effects meta-analysis, retention declined from 86.1% at 6 months to 80.2% at 12 months, 76.8% at 24 months and 72.3% at 36 months. Adjusting for variable follow-up time in a sensitivity analysis, 24 month retention was 70.0% (range: 66.7%-73.3%), while 36 month retention was 64.6% (range: 57.5%-72.1%). CONCLUSIONS: Our findings document the difficulties in retaining patients in care for lifelong treatment, and the progress being made in raising overall retention rates. PMID- 20586957 TI - Patient-reported barriers and drivers of adherence to antiretrovirals in sub Saharan Africa: a meta-ethnography. AB - This meta-ethnography aims at providing a synthesis and an interpretation of the findings of recent social science research on the questions of retention in antiretroviral therapy (ART) programmes in sub-Saharan Africa (SSA). The literature reviewed comprises ethnographic studies of the barriers to adherence to ART in various cultural settings. The results show that the quality of services, treatment-related costs, as well as the need to maintain social support networks - which can be negatively affected by HIV-related stigma - are important barriers to adherence. In addition, they show how African concepts of personhood are incompatible with the way services are conceived and delivered, targeting the individual. In SSA, individuals must balance physical health with social integrity, which is sometimes achieved by referring to traditional medicine. The ability of local concepts of illness to address social relations in addition to health, together with a historically grounded distrust in Western medicine, explains why traditional medicine is still widely used as an alternative to ART. PMID- 20586958 TI - Low retention of HIV-infected patients on antiretroviral therapy in 11 clinical centres in West Africa. AB - OBJECTIVE: To study factors associated with the probability of retention in antiretroviral therapy (ART) programmes in West Africa. METHODS: The International epidemiologic Databases to Evaluate AIDS (IeDEA) in West Africa is a prospective, operational, observational cohort study based on collaboration between 11 cohorts of HIV-infected adult patients in Benin, Cote d'Ivoire, Gambia, Mali and Senegal. All patients aged 16 and older at ART initiation, with documented gender and date of ART initiation, were included. For those with at least 1 day of follow-up, Kaplan-Meier method and Weibull regression model were used to estimate the 12-month probability of retention in care and the associated factors. RESULTS: In this data merger, 14 352 patients (61% female) on ART were included. Median age was 37 (interquartile range (IQR): 31-44 years) and median CD4 count at baseline was 131 cells/mm(3) (IQR: 48-221 cells/mm(3)). The first line regimen was NNRTI-based for 78% of patients, protease inhibitor-based for 17%, and three NRTIs for 3%. The probability of retention was 0.90 [95% confidence interval (CI): 0.89-0.90] at 3 months, 0.84 (95% CI: 0.83-0.85) at 6 months and 0.76 (95% CI: 0.75-0.77) at 12 months. The probability of retention in care was lower in patients with baseline CD4 count <50 cells/mm(3) [adjusted hazard ratio (aHR) = 1.37; 95% CI: 1.27-1.49; P < 0.0001] (reference CD4 > 200 cells/mm(3), in men (aHR = 1.17; 95% CI: 1.10-1.24; P = 0.0002), in younger patients (<30 years) (aHR = 1.10; 95% CI: 1.03-1.19; P = 0.01) and in patients with low haemoglobinaemia <8 g/dl (aHR = 1.33; 95% CI: 1.21-1.45; P < 0.0001). Availability of funds for systematic tracing was associated with better retention (aHR = 0.29; 95% CI: 0.16-0.55; P = 0.001). CONCLUSIONS: Close follow-up, promoting early access to care and ART and a decentralized system of care may improve the retention in care of HIV-infected patients on ART. PMID- 20586959 TI - Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa. AB - OBJECTIVE: To estimate loss to follow up (LTFU) between initial enrollment and the first scheduled return medical visit of a pre-antiretroviral therapy (ART) care program for patients not eligible for ART. METHODS: The study was conducted at a public-sector HIV clinic in Johannesburg. We reviewed records of all patients newly enrolled in the pre-ART care program and not yet eligible for ART between January 2007 and February 2008. Crude proportions of patients completing their first return medical visit stratified by patient characteristics were calculated. A modified-Poisson approach was used to estimate directly relative risks of returning for their first return medical visit within 1 year adjusting for patient characteristics as potential confounders. RESULTS: A total of 356 patients were identified. Two-thirds had a CD4 count > 350 cells/microl (median [IQR] CD4 = 458 [394, 585]) and were scheduled to return in 6 months for a first medical visit. Seventy-four percent of these patients did not return within one year for this visit. The remaining 36% of all patients had a baseline CD4 count 251-350 cells/microl and were scheduled to return in 3 months. Only 6% of these patients returned within 4 months; 41% returned within one year. Relative risks were positively associated with a patient being employed and negatively associated with the baseline CD4 count. CONCLUSIONS: Given the high rate of LTFU immediately after enrolling in pre-ART care, it is clear that care programs are not expediting the timely initiation of ART. Significantly improved adherence to pre-ART care and monitoring for patients not yet eligible for ART is required for South Africa to achieve its AIDS strategy goals and reduce the problem of late presentation and initiation of ART. PMID- 20586960 TI - Why are antiretroviral treatment patients lost to follow-up? A qualitative study from South Africa. AB - OBJECTIVES: To better understand the reasons why patients default from antiretroviral treatment (ART) programmes to help design interventions that improve treatment retention and ultimately, patient outcomes. METHODS: Prospective cohort study at two treatment sites in South Africa followed by qualitative interviews with patients that had defaulted. RESULTS: Respondents overwhelmingly reported that ART improved their health status and quality of life. Nevertheless, despite improved health from taking ART and worse health when treatment is stopped, serious barriers to treatment remained: transport costs, time needed for treatment, and logistical challenges were barriers to treatment, whereas stigma around HIV/AIDS, and side effects associated with ART were less influential. CONCLUSION: With a better understanding of the reasons for defaulting, interventions can be designed that improve treatment retention and ultimately, patient outcomes. This study argues for realistic interventions and policy changes designed to reduce the financial and time burden of ART and to reduce logistical barriers, such as simplifying the referral and transfer process, employing patient advocates, and adopting extended and weekend clinic hours. PMID- 20586961 TI - Vital status of pre-ART and ART patients defaulting from care in rural Malawi. AB - OBJECTIVES: To ascertain the outcome of pre-Antiretroviral therapy (ART) and ART patients defaulting from care and investigate reasons for defaulting. METHODS: Patients defaulting from HIV care in Chiradzulu between July 2004 and September 2007 were traced at last known home address. Deaths and moves were recorded, and patients found alive were interviewed. Defaulting was defined as missed last appointment by more than 1 month among patients of unknown vital status. RESULTS: A total of 1637 individuals were traced (54%-88% of eligible), 981 pre-ART and 656 ART patients. Of 694 pre-ART patients found, 49% had died (51% of adults and 38% of children), a median of 47 days after defaulting, and 14% had moved away. Of 451 ART patients found, 54% had died (54% of adults and 50% of children), a median of 52 days after defaulting, and 20% had moved away. Overall, 221 patients were interviewed (90% of those found alive), 42% had worked outside the district in the previous year; 49% of pre-ART and 19% of ART patients had not disclosed their HIV status to other household members. Main reasons for defaulting were stigma (43%), care dissatisfaction (34%), improved health (28%) and for ART discontinuation, poor understanding of disease or treatment (56%) and drug side effects (42%). CONCLUSION: This study in a rural African HIV programme reveals the dynamics related to health service access and use, and it provides information to correct programme mortality estimates for adults and children. PMID- 20586962 TI - Tracking a sample of patients lost to follow-up has a major impact on understanding determinants of survival in HIV-infected patients on antiretroviral therapy in Africa. AB - OBJECTIVE: To date, data regarding the determinants of mortality in HIV-infected patients starting antiretroviral therapy (ART) in Africa have been primarily derived from routine clinical care settings practicing the public health approach. Losses to follow-up, however, are high in these settings and may lead to bias in understanding the determinants of mortality. METHODS: We evaluated HIV infected adults initiating ART between January 1, 2004 and September 30th, 2007 in an ART clinic in southwestern Uganda. Clinical and demographic characteristics were obtained through routine clinical care. In evaluating determinants of mortality, a 'naive' analysis used only deaths known through routine processes. A 'sample-corrected' approach incorporated, through probability weights, outcomes from a representative sample of patients lost to follow-up whose vital status was ascertained through tracking in the community. RESULTS: In 3,628 patients followed for up to 3.75 years after ART initiation, the 'naive' approach identified male sex and lower pre-ART CD4 count as independent determinants of mortality. The 'sample-corrected' approach found lower pre-ART CD4 count, older age, lower weight and calendar year of ART initiation, but not male sex, to be independent determinants of mortality. CONCLUSIONS: Analyses to identify determinants of mortality in HIV-infected patients on ART in Africa that do not account for losses to follow-up can identify spurious associations and miss actual relationships - both with the potential to mislead public health efforts. A sampling-based approach to account for losses to follow-up represents a feasible and potentially scalable method to strengthen the evidence available for implementation of ART delivery in Africa. PMID- 20586963 TI - Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa. AB - The scale-up of antiretroviral therapy (ART) has been one of the success stories of sub-Saharan Africa, where coverage has increased from about 2% in 2003 to more than 40% 5 years later. However, tempering this success is a growing concern about patient retention (the proportion of patients who are alive and remaining on ART in the health system). Based on the personal experience of the authors, 10 key interventions are presented and discussed that might help to improve patient retention. These are (1) the need for simple and standardized monitoring systems to track what is happening, (2) reliable ascertainment of true outcomes of patients lost to follow-up, (3) implementation of measures to reduce early mortality in patients both before and during ART, (4) ensuring uninterrupted drug supplies, (5) consideration of simple, non-toxic ART regimens, (6) decentralization of ART care to health centres and the community, (7) a reduction in indirect costs for patients particularly in relation to transport to and from clinics, (8) strengthening links within and between health services and the community, (9) the use of ART clinics to deliver other beneficial patient or family-orientated packages of care such as insecticide-treated bed nets, and (10) innovative (thinking 'out of the box') interventions. High levels of retention on ART are vital for individual patients, for credibility of programmes and for on going resource and financial support. PMID- 20586964 TI - Situational analysis of varying models of adherence support and loss to follow up rates; findings from 27 treatment facilities in eight resource limited countries. AB - OBJECTIVES: Large-scale provision of ART in the absence of viral load monitoring, resistance testing, and limited second-line treatment options places adherence support as a vital therapeutic intervention. We aimed to compare patient loss to follow up rates with the degree of adherence support through a retrospective review of patients enrolled in the AIDSRelief program between August 2004 and June 2005. METHODS: Loss to follow up data were analysed and programs were categorised into one of four tiered levels of adherence support models: Tier I, II, III, and IV which increase from lowest to highest support. Bivariate and t test analyses were used to test for significant differences between the models. RESULTS: 13,391 patients at 27 treatment facilities from six African and two Caribbean countries began antiretroviral therapy within the first year of the AIDSRelief program. The mean loss to follow up within the first year was 7.5%. Eight facilities were Tier I, three (Tier II), nine (Tier III), and seven (Tier IV). Facilities in Tier I had a loss to follow up rate of 14%, Tier II (10%), Tier III (5%), and Tier IV (1%). The proportion of loss to follow up for Tier I and Tier III were significantly different from each other (P < 0.02), as were Tier I and Tier IV (P < 0.006). There were differences between Tier II and Tier IV (P < 0.009) as well as Tier III and Tier IV (P < 0.017). CONCLUSION: These data strongly support the use of proactive adherence support programs, beyond routine patient counselling and defaulter tracking to support the'public health approach'to ART. PMID- 20586965 TI - Early active follow-up of patients on antiretroviral therapy (ART) who are lost to follow-up: the 'Back-to-Care' project in Lilongwe, Malawi. AB - OBJECTIVES: To determine the proportion of patients returning to antiretroviral treatment (ART) and factors associated with their return in a resource-limited setting. METHODS: Between September 2006 and March 2009, at two ART-providing facilities in Lilongwe, Malawi, we identified patients who had missed clinic appointments by more than 3 weeks and therefore would have run out of antiretroviral drugs. We traced these individuals, documented reasons for missed appointments and, where appropriate, arranged another ART clinic appointment. RESULTS: Between April 2006 and March 2009, 2653 patients on ART had missed 3098 scheduled appointments. We successfully traced 85%, of whom 30% had died. Of the 1580 patients found alive, 25% had transferred to another ART clinic, 21% had collected drugs from other sources, 11% had treatment gaps; 40% had stopped taking drugs, 1% had not started taking drugs despite collecting them and 2% refused to be interviewed. Of the 1158 LTFU patients who had not died, transferred out or declined to be interviewed, 89% promised to return to their ART clinic and 74% actually did. The probability of returning to the clinic was significantly associated with being women, aged over 39 at ART initiation and having either treatment gaps or uninterrupted therapy. The B2C project reduced the proportion of patients finally classified as LTFU by 59%. CONCLUSION: Early active follow-up of LTFU patients resulted in marked improvement in known patient outcomes and improved retention in the treatment programme. PMID- 20586966 TI - Outcome assessment of decentralization of antiretroviral therapy provision in a rural district of Malawi using an integrated primary care model. AB - OBJECTIVE: To assess the effect of decentralization (DC) of antiretroviral therapy (ART) provision in a rural district of Malawi using an integrated primary care model. METHODS: Between October 2004 and December 2008, 8093 patients (63% women) were registered for ART. Of these, 3440 (43%) were decentralized to health centres for follow-up ART care. We applied multivariate regression analysis that adjusted for sex, age, clinical stage at initiation, type of regimen, presence of side effects because of ART, and duration of treatment and follow-up at site of analysis. RESULTS: Patients managed at health centres had lower mortality [adjusted OR 0.19 (95% C.I. 0.15-0.25)] and lower loss to follow-up (defaulted from treatment) [adjusted OR 0.48 (95% C.I. 0.40-0.58)]. During the first 10 months of follow-up, those decentralized to health centres were approximately 60% less likely to default than those not decentralized; and after 10 months of follow-up, 40% less likely to default. DC was significantly associated with a reduced risk of death from 0 to 25 months of follow-up. The lower mortality may be explained by the selection of stable patients for DC, and the mentorship and supportive supervision of lower cadre health workers to identify and refer complicated cases. CONCLUSION: Decentralization of follow-up ART care to rural health facilities, using an integrated primary care model, appears a safe and effective way to rapidly scale-up ART and improves both geographical equity in access to HIV-related services and adherence to ART. PMID- 20586967 TI - Cost of using a patient tracer to reduce loss to follow-up and ascertain patient status in a large antiretroviral therapy program in Johannesburg, South Africa. AB - OBJECTIVE: To evaluate a pilot intervention to engage a patient tracer to follow up lost patients at a large public clinic in South Africa. METHODS: A social worker spent 4 months contacting by telephone a random sample of patients who had initiated antiretroviral therapy (ART) at least 6 months earlier and were >or=1 month late for a scheduled visit. The tracer was authorized to assist patients to return to care if needed. Cost was calculated from the perspective of the clinic. RESULTS: The tracer was able to determine the final status of 260 of a sample of 493 lost patients. Of the 260, 55 (21%) had died, 56 (21%) were still on ART at the same site, 79 (30%) reported transferring to another site and 70 (27%) had discontinued treatment. Among those discontinuing, commonly cited reasons were relocation (n = 18, 26%), traditional medicine or religious beliefs (n = 11, 16%), fear of disclosure or other family barriers (n = 9, 13%), and employment obstacles (n = 7, 10%). Twenty patients returned to care at the original site as a result of the intervention, at an average cost of $432 per patient returned. CONCLUSIONS: A patient tracer was an effective way to determine the final status of lost patients and succeeded in returning some to care, but the cost per patient returned was high. Better information systems allowing sites to track deaths and transfers would greatly improve the efficiency of loss to follow-up interventions. PMID- 20586968 TI - Growing application of pharmacoeconomics and outcomes research in health-care decision-making in the Asia-Pacific region. PMID- 20586969 TI - Impact of diabetes mellitus (DM) on the health-care utilization and clinical outcomes of patients with stroke in Singapore. AB - OBJECTIVE: This study aims to assess the impact of diabetes mellitus (DM) on the health-care utilization and clinical outcomes of patients with acute stroke. METHODS: This is a retrospective cohort study. All patients who were admitted for the first time to one of the three public hospitals in the National Healthcare Group in Singapore from January 2005 to June 2007 with a primary diagnosis of acute stroke were included and were followed up for 1 year after the index hospitalization. The study population was divided into two groups: with DM and without DM. Both univariate and multivariate analyses were applied to compare the hospital length of stay (LOS), hospitalization costs, mortality, as well as the 1 year hospital readmissions between the DM and non-DM groups. RESULTS: There were 9766 study patients, and 38.5% of them had DM. DM patients with ischemic stroke (IS) and transient ischemic attack (TIA) stayed 1-day and 0.6-day longer, and incurred 10% and 26% higher hospital cost during index admission, respectively, compared with their counterparts in the non-DM group. They also had more hospital readmission within 1 year. The mortality rate in IS patients with diabetes was 24% higher. After risk adjustment, subarachnoid hemorrhage patients with diabetes had more hospitalizations. Intracerebral hemorrhage (ICH) and IS patients in the DM group had all worse outcomes but the 1-year stroke recurrence; TIA patients with DM incurred longer LOS and hospital costs. CONCLUSION: DM predicts worse clinical outcomes and higher health-care expenditures in the 1-year poststroke especially for the IS, ICH, and TIA stroke subtypes. PMID- 20586970 TI - The impact of health literacy on health-related quality of life (HRQoL) and utility assessment among patients with rheumatic diseases. AB - OBJECTIVES: The objective of this study was to investigate the impact of health literacy (HL) on health-related quality of life (HRQoL) and utility assessment among patients with rheumatic diseases. METHODS: HL was measured by the rapid estimate of adult literacy in medicine (REALM) and was characterized as low or adequate. HRQoL and utility scores were assessed using the SF-36, SF-6D, and EQ 5D. Comparisons of sociodemographics and HRQoL in patients with low or adequate HL were made using t test, chi-square, or Mann-Whitney U tests. Spearman's correlation and partial correlations were used to study the relationship between HL, HRQoL, and utility scores, with significant correlations further explored using multiple linear regression models. RESULTS: Data were analyzed from 199 subjects. Patients with adequate HL had significantly higher education levels, better dwelling status, lower disease activity, and better physical functioning (PF). There was a significant although weak correlation between HL level and PF. After adjustment, HL level was shown to independently explain 3.7% of the variance in the PF score. Nevertheless, there was no impact of HL on utility assessment or other HRQoL domains. CONCLUSION: HL did not impact HRQoL in general, but was found to have a weak impact on the PF of patients with rheumatic diseases. PMID- 20586971 TI - A survey of knowledge on diabetes in the central region of Thailand. AB - OBJECTIVES: The objectives of this study were to evaluate the level of knowledge of diabetes among the Thai general population, identify areas of deficiency for targeted health education effort, and identify respondent characteristics that may be associated with knowledge of diabetes. METHODS: A survey involving 1000 respondents (age > or = 15 years) was conducted in the central region of Thailand. A 42-item pre-tested questionnaire to assess general and specific knowledge of diabetes (e.g., risk factors, symptoms, treatment, etc.) was administered. Scores of <50%, > or =50% to <80%, and > or =80% were classified as "poor,""fair," and "good," respectively, according to expert consensus. RESULTS: Mean age of respondents was 33.8 years (SD 13.4), with 57.5% being female. Mean diabetes knowledge score was fair: 25.02 of 42 (59.6%), SD 8.35 (19.9%). Respondents performed best in the risk factor section: mean (%) score was 2.88 of 4 (72%), SD 1.11 (27.8%); and worst in the section on diabetes in women: mean (%) score was 0.82 of 3 (27.3%), SD 0.96 (32.0%). In multiple linear regression analyses, education level, older age, own self having diabetes, and having a family member/relative/friend with diabetes were significantly associated with knowledge of diabetes. CONCLUSIONS: Knowledge of diabetes among the Thai respondents was fair. Areas of deficiency and factors associated with knowledge of diabetes were identified. Our findings would be useful in informing targeted health education programs. PMID- 20586972 TI - A catalogue of EQ-5D utility weights for chronic diseases among noninstitutionalized community residents in Korea. AB - OBJECTIVE: The main purpose of this study is to provide a national catalog of preference-based utility weights associated with major chronic diseases in Korea. METHODS: The 2005 Korea National Health and Nutrition Examination Survey was used to get EQ-5D scores for 27 major chronic diseases. The independent detrimental effect of each chronic disease was estimated using a censored least absolute deviations regression. RESULTS: The respondents (60.5%) rated their health as perfect or 11111 on the EQ-5D scale showing ceiling effect. Stroke (0.5067 approximately 0.5756) was the condition of the lowest EQ-5D utility weight and was followed by renal failure (0.6637 approximately 0.7739), angina pectoris (0.7325 approximately 0.8364), and arthritis (0.7621 approximately 0.8644). The marginal impact of each chronic disease after adjusting for age, sex, education, income, marital status, and the number of comorbid conditions was largest in stroke, arthritis, cancer, renal failure, and herniated disc. CONCLUSION: This study provided a nationally representative catalog of utility weights for major chronic diseases in Korea. The three most burdensome chronic diseases among Korean adults based on the regression analysis were stroke, arthritis, and cancer. PMID- 20586973 TI - Relapse and long-acting injectable risperidone: a 1-year mirror image study with a national claims database in Taiwan. AB - OBJECTIVES: The development of long-acting, injectable atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The study was designed to assess whether a risperidone long-acting injection (RLAI) is associated with reduced relapses and service utilization in the real world. METHODS: The Psychiatric Inpatients Medical Claims dataset was used for the analysis. It is a longitudinal dataset that includes the National Health Insurance claims of service uses by a cohort of mentally ill patients. The inclusion criteria for this analysis were patients who: 1) had available information for at least 12 months after the first dose of RLAI; 2) had a primary diagnosis of schizophrenia; and 3) were regularly treated with RLAI for at least 1 year. Patients who accumulatively received at least 75-mg RLAI per 3-month period were considered to be undergoing regular treatment. Wilcoxon signed rank tests were performed to compare differences in numbers of acute admissions, hospital days, emergency room visits, and relapses between the pre- and post-RLAI periods in this 1-year mirror image study. RESULTS: In total, 108 patients were eligible for analysis. Significant reductions in the total annual numbers of acute hospital admissions by 55% (80 vs. 36, P = 0.0003), hospital days by 48% (4106 vs. 2126, P = 0.0021), and relapses by 54% (115 vs. 53, P = 0.0005) were observed. A reduction of emergency room visits was also observed, but did not reach statistical significance (55 vs. 25, P = 0.1255). CONCLUSIONS: This 1-year mirror-image analysis with claims-based data demonstrated that RLAI treatment was associated with reductions in relapses and hospital service utilization. PMID- 20586974 TI - Evidence-based decision-making on medical technologies in China, Japan, and Singapore. AB - OBJECTIVE: To review the use of evidence in the market approval process, reimbursement, and price control mechanisms for medicines and medical devices in China, Japan, and Singapore. METHODOLOGY: Documentary reviews relevant to public health policy and management by government authorities. RESULTS: Drug regulatory authorities play a vital role in the market authorization process of medical technologies. The approval criteria in the three countries are similar to those of the US Food and Drug Administration and many other countries, whose core measures are efficacy, safety, and quality, along with risk-based analyses in China and Singapore. All established the national drug list (Japan) or lists (China and Singapore) for reimbursement. Although Japan reimburses any drugs listed, China and Singapore selectively reimburse regarding the types of the list. The cost-effectiveness is utilized for prioritization of new drugs listed in Singapore. Japan controls the price by government, whereas Singapore keeps market liberalism, and China maintains a mixture of both. CONCLUSION: All three countries have established their own mechanisms, but cost-effectiveness requirements have not been fully introduced yet, partially applied to the reimbursement processes in Singapore. PMID- 20586975 TI - Evidence-based decision on medical technologies in Asia Pacific: experiences from India, Malaysia, Philippines, and Pakistan. AB - BACKGROUND: This paper discusses national programs implemented in India, Pakistan, Malaysia, and Philippines to generate and apply evidence in making informed policy decisions on the approval, pricing, reimbursement and financing of medicines, diagnostics, and medical devices. APPROVAL: In all countries, the Ministries of Health are generally responsible for approval of health technologies through various agencies like the Central Drugs Standard Control Organisation in India, Bureau of Food and Drugs for medicines and Bureau of Health Devices and Technology for medical devices in the Philippines, the National Pharmaceutical Control Bureau, Health Technology Assessment Unit and Medical Device Bureau in Malaysia, and the Drug Control Organization in Pakistan. Product dossiers are evaluated while taking decisions. PRICING CONTROL: India has a strong price control mechanism through the National Pharmaceutical Pricing Authority. In the Philippines, the Essential Drug Price Monitoring System monitors prices of 37 essential drugs monthly from all drugstore outlets nationwide. In Malaysia and Pakistan registration pricing of new drugs is negotiated/fixed by the government with the vendor. REIMBURSEMENT: A mix of social, voluntary private and community-based health insurance plans are available in India while the Philippine Health Insurance Corporation is responsible for reimbursement of drugs and medical devices in the Philippines. In Malaysia no formal reimbursement system is being practiced, and in Pakistan the government reimburses medical claims of its employees. FINANCING: In both India and the Philippines the bulk of health expenditure is out of pocket while the government pays for 20% and 28% respectively in both countries. The public health care services in Malaysia are heavily subsidized by the government with minimum fee being charged to the public. The government of Pakistan gives free medicines to its citizens at the public health facilities. CONCLUSIONS: In the region under discussion, one of the priority areas that the different regulatory agencies would benefit from is human resource development to facilitate the process of evidence based assessment of health technologies. Higher budgetary allocation and stronger legislation is also needed along with interagency and international coordination and cooperation to harmonize. PMID- 20586976 TI - Using economic evaluation in policy decision-making in Asian countries: mission impossible or mission probable? AB - OBJECTIVES AND METHODS: This article provides an extensive review of literature and an in-depth analysis aimed at introducing potential applications of economic evaluation and at addressing the barriers that could prohibit the use or diminish the usefulness of economic evaluation in Asian settings. It also proposes the probable solutions to overcome these barriers. RESULTS: Potential uses of economic evaluation include the development of public reimbursement lists, price negotiation, the development of clinical practice guidelines, and communicating with prescribers. Two types of barriers to using economic evaluation, namely barriers relating to the production of economic evaluation data and decision context-related barriers, are identified. For the first sort of barrier, the development of the national guidelines, the development of economic evaluation database, planning and use of economic evaluation in a systematic manner, and prioritization of topics for assessment are recommended. Furthermore, educating potential users and the public, making the economic evaluation process transparent and participatory, and incorporating other health preferences into the decision-making framework have been promoted to conquer decision context related barriers. CONCLUSIONS: It seems practically impossible to adopt other countries' approaches using economic evaluation for priority setting because of several constraints specifically related to the context of each setting. Nevertheless, given a better understanding of its resistance, and proper policies and strategies to overcome the barriers applied, it is more than probable that a method with system/mechanisms specifically designed to fit particular settings will be used. PMID- 20586978 TI - The current capacity and future development of economic evaluation for policy decision-making: a survey among researchers and decision-makers in Thailand. AB - OBJECTIVE: This study aims to explore the knowledge, experience, and attitudes toward economic evaluation (EE) among decision-makers and researchers in Thailand. METHODS: Researchers were purposively selected from Thai academics and both public and private research organizations related to EE. Decision-makers at the provincial level were purposively selected from the members of the Management Committees of Provincial Health Offices, and those at hospital level were randomly selected from members of the public and private hospital formulary drug committees throughout Thailand. The self-administered postal questionnaires were distributed. Univariate and bivariate analyses were applied. RESULTS: Of the total 2575 questionnaires distributed, 758 (29.4% response rate) were completed and sent back. The majority of researchers and decision-makers were not familiar with technical terms commonly used in health EE, e.g., incremental cost effectiveness ratio, discounting, and sensitivity analysis. More decision-makers (70.6%) had never had EE training compared to researchers (50.0%). Both roles indicated that value for money was one of the important issues to consider for health technology adoption. CONCLUSIONS: An extensive unmet demand for EE training among Thai researchers and decision-makers still exists. Findings from this study contribute to the short- and long-term plans for research capacity building. PMID- 20586979 TI - Pharmacoeconomic guidelines and their implementation in the positive list system in South Korea. AB - This article reviews the change in the reimbursement and pricing system in South Korea, which was the precursor to the eventual implementation of evidence-based decision-making. There has been pressure on Korea's National Health Insurance system to control its skyrocketing expenditures on drugs. As a result, a series of cost-containment policies have been implemented. The idea of economic evidence based decision-making was first introduced in Korea in 2001 when the government announced cost-effectiveness as one of the criteria for reimbursement decisions. After this announcement, the Health Insurance Review and Assessment Service (HIRA) developed guidelines, which became the standard for economic evaluations. In 2006, the drug listing system for reimbursement was changed from a negative to a positive system under the drug expenditure rationalization plan. Under this new system, only drugs that are proven economically and clinically valuable can be listed, and applicants have to submit economic evaluation studies to support the cost-effectiveness of their drugs. Once new applications are submitted, HIRA reviews them, and the Drug Reimbursement Evaluation Committee (DREC) decides whether or not to recommend the submitted drugs. In its reimbursement decisions, the DREC considers not only cost-effectiveness but also the availability of therapeutic alternatives, the severity of the condition treated, and the impact on the budget, among other measures. After the introduction of the positive list system, 56% of drugs were determined to be appropriate for reimbursement by the DREC. Despite limited human resources, experience, and quality local data, Korea is continuing to make efforts to establish a system of evidence-based decision making. PMID- 20586980 TI - Evidence-based decision-making in Asia-Pacific with rapidly changing health-care systems: Thailand, South Korea, and Taiwan. AB - OBJECTIVE: To review the use of evidence in the market approval process, reimbursement, and price control mechanisms for medicines and medical devices in Thailand, South Korea, and Taiwan. METHODS: Documentary reviews supplemented by interviews with senior policymakers of relevant public health authorities. RESULTS: Drug regulatory authorities play a vital role in the market authorization process by considering evidence on safety, efficacy and quality for new medicines, and bio-equivalence for new generic products of previously patented medicines. For the formulation of the reimbursement list, all three cases applied evidence on cost-effectiveness, to various degrees, with clear institutional structure, capacity, and functions. Only Thailand has specified an explicit benchmark on cost-effectiveness for inclusion in the reimbursement list. For price control, all have established mechanisms and processes for price negotiation. These mechanisms apply evidence on cost structure and relative prices in other countries to ensure affordable prices, especially with the patented drug industry. Thailand's universal insurance schemes use a capitation payment model which proves effective in implicit price control. To increase access to essential medicines that have patents on and high price, Thailand applied Trade-Related Aspects of Intellectual Property flexibilities; "government use of patent," for public noncommercial purposes to seven essential drugs in 2006 to 2008. CONCLUSION: Rapidly increasing health expenditure and universal health insurance systems have created greater requirement for proof of "value for money" in the approval and funding of new medical technologies. All settings have established clear mechanisms to apply appropriate evidence in the processes of market approval, reimbursement, and pricing control. PMID- 20586981 TI - Economic evaluation of universal infant vaccination with 7vPCV in Hong Kong. AB - OBJECTIVES: The purpose of this study was to evaluate the clinical and economic benefits of routine infant vaccination with seven-valent pneumococcal conjugate vaccine (7vPCV) in Hong Kong. METHODS: A decision-analytic model was populated with local age-specific incidence data to simulate the expected health outcomes resulting from 7vPCV vaccination of a birth cohort of 57,100 children compared with an unvaccinated cohort over a 10-year horizon. Primary analyses were conducted from a payer perspective, using local inpatient and outpatient costs associated with the treatment of pneumococcal disease. Vaccine efficacy rates were consistent with results from pivotal clinical trials. The reduction in adult invasive pneumococcal disease (IPD) and associated cost avoidance due to the indirect effect of vaccination were estimated in line with published overseas rates. RESULTS: Universal 7vPCV vaccination was estimated to prevent 524 cases of IPD and more than 2580 cases of otitis media in the birth cohort over a 10-year period, leading to a reduction of HK$28.7 million (US$3.7 million) in direct medical costs. Additional cost savings from the indirect prevention of 919 adult cases of IPD during this time period also resulted. Overall, 7vPCV vaccination was estimated to have an incremental cost per life-year gained of HK$50,456 (US$6460) from a payer perspective or HK$46,308 (US$5929) when both direct and indirect costs were included. CONCLUSION: With reference to the World Health Organization's threshold for cost-effectiveness, results from this study indicate that routine infant vaccination with 7vPCV is a cost-effective intervention because of the added cost savings resulting from the indirect effect of vaccination on adult disease. PMID- 20586982 TI - Modeling the cost-effectiveness of galantamine for mild to moderately severe Alzheimer's disease in Korea. AB - OBJECTIVE: The aim of the study was to determine the cost-effectiveness, from the third-party payer viewpoint, of galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease (AD). METHODS: An existing Markov model was adapted to Korea to predict long-term outcomes over a 5 year time horizon and to estimate the cost-effectiveness of galantamine for the treatment of AD. The model structure is informed by a review of national and international literature on the clinical and cost-effectiveness of galantamine and on the costs and outcomes associated with treatment for AD. The main outcome measure used was the cost per quality-adjusted life year (QALY) gained. All costs were indexed to US$ (2007 value). Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. RESULTS: The study findings indicate that the clinical benefits on AD progression from galantamine treatment resulted in an incremental cost per QALY gained of US$4939 over 5 years (vs. usual care). Probabilistic sensitivity analysis and cost-effectiveness acceptability curve suggest that the probability of galantamine treatment having an incremental cost per QALY over US$6740 is zero. Incremental cost per QALY gained according to scenario analyses ranged from US$2271 to US$8335. CONCLUSION: These findings suggest that the use of galantamine may be a cost-effective use of Korean national health-care resources, considering the gross domestic product per capita of US$21,695 in 2007. PMID- 20586984 TI - Cost-effectiveness analysis of oseltamivir for influenza treatment considering the virus emerging resistant to the drug in Japan. AB - AIM: The purpose of this study is to evaluate the cost-effectiveness of oseltamivir for influenza in Japan considering the complications and the emergence of oseltamivir-resistant virus. METHODS: Study design is a cost effectiveness analysis in decision analytic modeling based on previously published evidence. Outcome measures included costs and quality-adjusted life year (QALY). RESULTS AND CONCLUSION: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of oseltamivir during influenza and complications was JPY398,571 ($3320) per QALY without productivity loss, which implied oseltamivir is evidently cost-effective. Furthermore, considering the productivity loss, the ICER for oseltamivir turned to be negative, which means simply dominant. When the prevalence was in the low range of 10% to 38%, oseltamivir became less cost-effective than conventional treatment. Regarding potential emergence of the drug-resistant virus, we found the dominance of oseltamivir will vanish if the emerging rate becomes larger than 27%. The two-way sensitivity analysis also suggested that if the resistant virus rate becomes less and the prevalence higher, then oseltamivir becomes more advantageous. The analysis for uncertainty, using cost-effectiveness acceptability curve by Monte Carlo simulation, resulted in the estimate of about 80% chance that oseltamivir could be cost-effective at the willingness-to-pay level of JPY6,000,000 ($50,000), which is commonly accepted as an affordable threshold. PMID- 20586983 TI - Cost-effectiveness of switching to biphasic insulin aspart 30 from human insulin in patients with poorly controlled type 2 diabetes in South Korea. AB - OBJECTIVES: To estimate the cost-effectiveness of switching patients with poorly controlled type 2 diabetes mellitus from human insulin (HI) to biphasic insulin aspart 30 (BIAsp 30) in South Korea. METHODS: A published and validated diabetes computer simulation model (the IMS CORE Diabetes Model) was used to evaluate the long-term clinical and economic outcomes associated with switching to BIAsp 30, using treatment effects from the South Korean subgroup of the Physician's Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy study and cost data collected through primary research. Outcomes included life expectancy, quality adjusted life expectancy, incidence of complications, direct medical costs, and cost-effectiveness. Analyses were performed from a third-party payer perspective over a 30-year time horizon. Future costs and clinical benefits were discounted at 5% per annum. Extensive sensitivity analyses were performed. RESULTS: Switching patients uncontrolled on HI to BIAsp 30 was projected to increase discounted mean life expectancy by 0.15 +/- 0.18 years per patient (8.62 +/- 0.13 years vs. 8.47 +/- 0.13 years) and improve discounted mean quality-adjusted life expectancy by 0.30 +/- 0.12 quality-adjusted life-years (QALYs) per patient (5.68 +/- 0.09 QALYs vs. 5.38 +/- 0.09 QALYs). Conversion to BIAsp 30 was associated with a mean increase in direct costs of South Korean Won (KRW) 1,777,323 +/- 359,209 over patient lifetimes. BIAsp 30 was associated with an incremental cost effectiveness ratio of KRW5,916,758 per QALY gained versus HI. CONCLUSION: Switching patients uncontrolled on HI to BIAsp 30 was projected to improve life expectancy and quality-adjusted life expectancy. This analysis suggests that BIAsp 30 could be a cost-effective treatment option in type 2 diabetes patients poorly controlled on HI in South Korea. PMID- 20586985 TI - Cost-effectiveness of long-acting risperidone injection versus alternative atypical antipsychotic agents in patients with schizophrenia in China. AB - OBJECTIVES: To determine the most cost-effective strategy involving first-line treatment with long-acting risperidone, olanzapine, and quetiapine from the perspective of the Chinese health-care system. METHODS: A decision analytical model was applied. The model used a time horizon of 2 years. The probabilities of treatment response of different agents and the relapse and hospitalization rates were estimated by a Delphi panel of 17 senior psychiatrists in China. The unit cost for each medical service was calculated from the price system database built by China National Development and Reform Commission and the medical resource utilization was estimated by the Delphi panel. The principal efficacy measure was the proportion of patients successfully treated. Various sensitivity analyses were carried out to test the robustness of the model. RESULTS: The proportion of patients successfully treated over the 2-year period was 46.71% for long-acting risperidone, 39.93% for olanzapine, and 31.28% for quetiapine. The mean cost effectiveness ratios were RMB189,427, RMB202,432, and RMB233,015 per successfully treated patient for long-acting risperidone, quetiapine and olanzapine, respectively. Results of the sensitivity analyses confirmed that the results were robust. CONCLUSIONS: The results showed that long-acting risperidone is more cost effective than olanzapine and quetiapine for patients with schizophrenia in long term maintenance treatment. PMID- 20586986 TI - Evaluation of cost-utility of varenicline compared with existing smoking cessation therapies in South Korea. AB - OBJECTIVE: This study aimed to evaluate the cost-effectiveness of varenicline compared with the other smoking cessation interventions, bupropion, nicotine replacement therapy (NRT), and willpower. METHODS: The Benefits of Smoking Cessation on Outcomes model was modified to reflect major smoking-related diseases in Korea. Transitional probabilities, resource utilization, and costs were obtained from Korean public data. The analysis was carried out from a societal perspective for the lifetime period. Also, series of sensitivity analyses, including probabilistic sensitivity analysis, were performed. RESULTS: With the exclusion of bupropion, which is subject to extended dominance, the incremental cost-effectiveness ratio (ICER) for varenicline versus NRT was analyzed as $US4809 per quality-adjusted life-year (QALY) during the lifetime. The results of sensitivity analysis are quite stable across most of the included parameters. The acceptability curves showed that the probability of varenicline being cost-effective was 83.3% at the willingness to pay of $US15,000. CONCLUSIONS: Even though the maximum willingness to pay for a QALY has not officially been defined, varenicline can be regarded as cost-effective because the ICER is at the 24.0% level of per capital gross domestic product, which is an implicit reference for decision-making in Korea. PMID- 20586987 TI - Valuation of the economic benefits of human papillomavirus vaccine in Taiwan. AB - OBJECTIVES: The study aims to apply the contingent valuation method to elicit the willingness-to-pay (WTP), and measure the value of a statistic life (VSL), for human papillomavirus (HPV) vaccine in Taiwan. METHODS: A total of 512 questionnaires were completed on women aged 20 to 55 years with at least one daughter, during March through May 2007. The respondents' WTP for the vaccines was elicited by double-bounded binary-choice questions under two scenarios: one was to protect themselves from cervical cancer (CC) and the other was for their daughter(s). The WTP was modeled as a function of the respondents' knowledge score, attitudes toward CC and HPV vaccine, the vaccination outcome scenarios, and individual characteristics. A log-normal survival model was constructed and the maximum-likelihood method was used for estimation. RESULTS: The median regression-adjusted WTP was estimated at US$1098 to US$1233 (US$913-1004) for vaccinating the daughter (mother); and the VSL was estimated at approximately US$0.65 to US$4.09 (US$0.56-3.16) million for vaccinating the daughter (mother). CONCLUSIONS: The study results provided important evidences on the monetary value women placed on a HPV vaccine, and the differential benefits between vaccinating the women and their daughters. PMID- 20586988 TI - A time-cost augmented economic evaluation of oral deferasirox versus infusional deferoxamine [corrected] for patients with iron overload in South Korea. AB - OBJECTIVES: This study aims to conduct an economic evaluation of oral deferasirox (DSX) compared with infusional deferoxamine (DFO) in patients with transfusional iron overload. METHODS: Depending on the methods for measuring time-cost and convenience associated with the mode of administration, either cost-utility analysis or cost-effectiveness analysis was undertaken. The difference in compliance rate between DSX and DFO was applied. RESULTS: Although the drug cost of DSX was US$124,070 higher than that of DFO (US$96,039 vs. US$220,199), all other costs were lower in patients with DSX than in patients with DFO. In the cost-utility analysis, DSX resulted in US$3197 savings with a gain of 2.63 quality-adjusted life-years per patient. The result of the cost-effectiveness analysis also showed that DSX dominated DFO. CONCLUSIONS: With a considerable improvement in convenience and injection time rather than efficacy, DSX is considered as a dominant therapy for patients with iron overload. PMID- 20586989 TI - An economic evaluation of adjuvant trastuzumab therapy in HER2-positive early breast cancer. AB - OBJECTIVE: One-year adjuvant trastuzumab therapy increases disease-free and overall survival in the adjuvant treatment of early HER2-positive breast cancer. This study aims to assess the long-term cost-effectiveness of adjuvant trastuzumab treatment in Beijing, Shanghai, and Guangzhou. METHODS: A Markov health-state transition model was constructed to simulate the natural development of breast cancer based on HERceptin Adjuvant (HERA) trial, estimate costs and disease progression over a lifetime perspective with annual transition cycles, and evaluate the cost-effectiveness of 1-year adjuvant trastuzumab treatment group compared with the standard adjuvant chemotherapy. From the perspective of a China health insurance system, cost was calculated based on a survey from clinical expert panels. RESULTS: On the basis of HERA data, the model results showed that the utilization of adjuvant trastuzumab treatment in early breast cancer can prolong 2.87 life years, compared with the standard chemotherapy group. The incremental cost for an additional life-year gained (LYG) was US$7564, US$7933, and US$7929 in Beijing, Shanghai, and Guangzhou, respectively. If measured by quality-adjusted life-year, the incremental cost-effectiveness ratio was US$7676, US$8049, and US$8046, respectively. CONCLUSION: The results suggest that the 1-year adjuvant trastuzumab treatment is cost-effective. Both clinical and economic benefits were superior for the 1-year adjuvant trastuzumab treatment group compared with the standard adjuvant chemotherapy group. PMID- 20586990 TI - Cost-effectiveness study comparing imatinib with interferon-alpha for patients with newly diagnosed chronic-phase (CP) chronic myeloid leukemia (CML) from the Chinese public health-care system perspective (CPHSP). AB - OBJECTIVE: Imatinib, a breakthrough oral molecular-targeted therapy, has demonstrated durable responses and significant survival advantage compared with interferon-based treatment. This study compares imatinib with interferon in newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) patients from the Chinese public health-care system perspective (CPHSP). METHODS: One-year cost responder and lifetime cost-utility analyses were conducted, respectively. Complete cytogenetic response was used to define a responder. Direct medical costs were included. Response rates as well as survival estimates were obtained from published literature. RESULTS: The cost per responder for interferon was close to 20 times higher than that for imatinib. The cost per additional responder was RMB36,545. The incremental cost-effectiveness ratio (ICER) comparing imatinib with interferon was RMB73,674 (95% confidence interval RMB67,712-RMB79,637) per quality-adjusted life-year. CONCLUSION: In newly diagnosed CML-CP, the cost per responder for patients treated with imatinib is much lower than that for patients treated with interferon. In the cost-utility analysis, the ICER is below the cost-effectiveness threshold recommended by the World Health Organization for developing countries. Therefore, imatinib is more cost-effective than interferon from the CPHSP. PMID- 20586991 TI - Assessment of total economic burden of chronic hepatitis B (CHB)-related diseases in Beijing and Guangzhou, China. AB - OBJECTIVE: To estimate the total annual cost due to Chronic Hepatitis B (CHB) related diseases imposed on each patient and his/her family in Beijing and Guangzhou, China. METHODS: Economic burden of CHB-related diseases (CHB, compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma) were examined. A retrospective cohort of 328 patients in Beijing and 271 in Guangzhou were identified to obtain their socioeconomic status, utilization and costs of treatment, and work loss days due to illness with a structured questionnaire. Costs of hospitalization were extracted from databases of two hospitals in Beijing and Guangzhou Social Insurance Information System, respectively. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients, while the inpatient cost was calculated through annual rate of hospitalization and average expenditure for different types of hospitals. Self medication and direct nonmedical cost were also reported. The Human Capital Approach was employed to measure the work loss cost. RESULTS: The total annual cost per patient for CHB, compensated cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma were US$1636, US$2722, US$4611, and US$6615 in Beijing, and US$1452, US$2065, US$4290 and US$6054 in Guangzhou, respectively. CONCLUSION: This study confirms that CHB-related diseases impose a substantial economic burden on patients, families, and the society in China urban areas. The study demonstrates increasing health-care costs related to disease progression and provides useful information on cost of treatment and work loss for different disease states, which can be further utilized in cost-effectiveness evaluation. PMID- 20586992 TI - Estimating medical expenditure associated with osteoporotic hip fracture in elderly Korean women based on the National Health Insurance Claims Database 2002 2004. AB - OBJECTIVES: To estimate the medical expenditure associated with osteoporotic hip fracture in elderly Korean women from insurer's perspective. METHODS: All claim records of women aged > or =50 years and diagnosed with hip fracture from 2002 to 2004 were obtained from the Korean National Health Insurance. The first 6 months were considered a "window period" during which patients with fractures were defined as incident cases if their initial records of visit or admission were observed after June 30, 2002. We included only those with claim records showing diagnosis of osteoporosis or prescription for antiosteoporosis drugs. For each patient, we calculated the cumulative claims amount related to the initial and follow-up treatment for 2 years after fracture. RESULTS: A total of 22,247 patients were identified during 2.5 years. During the first year of fracture, an average of 3.28 visits and 0.97 admissions were recorded; during the second year, 0.35 visits and 0.02 admissions were recorded. The 2-year cost per patient was KRW3,175,467, 97.4% of which was incurred during first year. CONCLUSION: Exploring the economic burden of osteoporotic hip fracture in the elderly women is expected to motivate policymakers and clinicians to adopt effective treatment options for the disease prevention and expenditure control. PMID- 20586993 TI - Economic impact on health-care costs related to major diseases including HIV/AIDS due to alcohol drinking among Thai populations. AB - OBJECTIVE: The objective of this study was to estimate health-care costs because of diseases caused by alcohol consumption based on health system's perspective. METHODS: Total direct health-care costs of alcohol drinking were the summation of the costs of alcohol drinking in inpatient and outpatient departments due to chronic diseases and acute conditions using prevalence-based approach. The alcohol-attributable fractions, defined as the proportion of a disease or acute condition in a population attributable to alcohol drinking, were calculated to obtain the number of patients in each disease or acute condition attributable to alcohol drinking. Health-care costs of alcohol drinking were estimated by multiplying the number of patients in each disease category attributable to alcohol drinking with the unit cost of treatment. RESULTS: Total health-care costs attributed to alcohol in this research were 5491 million baht (i.e., outpatient department [2488 million baht] and inpatient department [3003 million baht]). Cost derived from inpatient department accounted for 55% of the total health-care cost attributed to alcohol. CONCLUSIONS: The result of this study suggested that alcohol drinking was significantly associated with a large number of health-care costs in Thailand. Estimation of health-care costs related to alcohol drinking would provide an important insight into future policy appraisal and evaluation. PMID- 20586994 TI - Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis. AB - Chelated zinc-carnosine and vitamin E [GastriCalm((r)) (GCM); Teva Animal Health] is marketed as an anti-emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double-blinded, placebo-controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica((r)); Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n=30) or placebo (n=30) groups. All dogs received ~ 5 mg/kg ciclosporin (range, 3.5-5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs >= 13.6 kg received one tablet once daily. GastriCalm((r)) or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty-one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty-seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P=0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P<0.05). PMID- 20586995 TI - Longitudinal investigation of methicillin-resistant Staphylococcus aureus in piglets. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important public health concern and pigs have been implicated in human infections. Cross sectional studies have demonstrated that MRSA can be commonly found in pigs internationally, but little is known about age-related changes in MRSA colonization. This study evaluated MRSA colonization in piglets in a longitudinal manner. Serial nasal swabs were collected from piglets born to 10 healthy sows. The prevalence of MRSA colonization on days 1, 3, 7, 14 and 21 was 1% (1/100), 6.2% (3/97), 8.5% (8/94), 4.4% (4/91) and 20% (18/91) respectively, with an overall pre-weaning prevalence of 34.5%. The prevalence on days 28, 42, 56 and 70 was 34% (31/91), 65% (57/88), 50% (44/88) and 42% (36/87) respectively, with an overall post-weaning prevalence of 85%. Eighty-four percent of piglets from negative sows and 100% of piglets from positive sows that survived at least until the time of weaning were colonized with MRSA at one or more times during the study. There was a significant association between sow and piglet colonization. The age of the piglet was significantly associated with the probability of colonization. No piglets or sows received antimicrobials during the study period. These results indicate that age must be considered when designing surveillance programmes and interpreting results of different studies on MRSA. PMID- 20586996 TI - Secular trends of sports participation, sedentary activity and physical self perceptions in Hong Kong adolescents, 1995-2000. AB - AIM: To assess the 5-year secular changes in sports participation, sedentary activity, and physical self-perceptions among Hong Kong adolescents. METHODS: A total of 2932 and 5692 secondary students, aged 13-18 participated in the Health Related Behavior General (HRBG) Survey in 1995-1996 and 2000-2001, respectively. Extracurricular sports participation at least weekly or as a team member (none, 1 2 events, 3 or more events), sedentary activities (0-1 h/day, 2 h/day or more) including television/video watching and homework were assessed. Additionally, physical self-perceptions, physical fitness (fit/very fit, moderately fit, unfit/very unfit) and body weight (intention to lose weight, satisfied, intention to gain weight) were reported. Secular trends of sports participation, and sedentary activities and physical self-perceptions were assessed. RESULTS: During the 5 years, the prevalence of sports participation (at least weekly or membership) decreased significantly in boys. The prevalence of both TV/video watching and homework for at least 2 h/day increased significantly in both sexes. The prevalence of being unfit/very unfit increased significantly in girls. No significant secular difference in weight perception was observed for both sexes. CONCLUSIONS: Sports participation decreased and sedentary activities increased during the 5-year period. Physical self-perceptions did not change significantly, except an increase in being physically unfit was observed in girls. PMID- 20586997 TI - Early predictors of hypertension in prematurely born adolescents. AB - OBJECTIVE: To assess the blood pressure of former preterm and term matched adolescent controls and to identify risk factors associated with blood pressure at 16 years. DESIGN: Observational cohort study. Secondary analysis of a randomized clinical trial. SETTING: Three academic centres participating in the Multicenter Indomethacin IVH Prevention Trial. PARTICIPANTS: A total of 296 children born in 1989-1992 with birth weights 600 to <1250 g who participated in the Multicenter Indomethacin IVH Prevention Trial and 95 term controls were evaluated at 16 years. MAIN OUTCOME MEASURES: Blood pressure and predictors of blood pressure. RESULTS: The adjusted mean difference in blood pressure for preterm adolescents was 5.1 mm Hg; p=0.002 for systolic and 2.1 mm Hg; p=0.027 for diastolic blood pressure. Among preterms, the primary predictors of increased systolic blood pressure were weight gain velocity between birth and 36 months (b=8.54, p<0.001), pre-eclampsia (b=5.67, p=0.020), non-white race (b=3.77, p=0.04) and male gender (b=5.09). Predictors of diastolic blood pressure were weight gain velocity between birth and 36 months (b=4.69, p=0.001), brain injury (b=6.51, p=0.002) and male gender (b=-2.4, p=0.02). CONCLUSIONS: Early programming secondary to increased early weight gain velocity, intrauterine stress and neonatal brain injury may all contribute to risk of increased blood pressure among former preterm adolescents. PMID- 20586998 TI - Childhood stroke in Sweden I: incidence, symptoms, risk factors and short-term outcome. AB - AIM: To evaluate the incidence, presenting symptoms, diagnostic delay, risk factors and short-term outcome of childhood stroke in a population-based cohort of Swedish children. METHODS: We retrospectively reviewed the records of children experiencing their first stroke during a 7-year period in Uppsala-Orebro Health Care Region covering one-fifth of the Swedish population. Arterial ischaemic stroke (AIS), cerebral sinus venous stroke and nontraumatic haemorrhagic stroke (HS) in children aged > 28 days and < 18 years were included. RESULTS: We identified 51 children (23 boys and 28 girls; median age 13). The average annual incidence of stroke was 1.8 per 100,000 children. AIS was found in 51% of the children, HS in 41% and cerebral sinus venous stroke in 8%. One-third of the children had underlying diseases, and one-third had vascular malformations. Six girls used oral contraceptives, three of these were smokers and two had iron deficiency anaemia. Two children died in the acute stage (4%), and 40/49 (82%) had some neurological dysfunction at discharge. CONCLUSION: The incidence of childhood stroke was 1.8 per 100,000 children and year, and the primary mortality was 4%. Risk factors of importance were oral contraceptives, smoking and anaemia in combinations. PMID- 20586999 TI - Incontinentia pigmenti revisited. A novel nonsense mutation of the IKBKG gene. AB - AIM: To describe and evaluate the clinical and molecular findings of patients with incontinentia pigmenti (IP) in Greece. METHODS: We examined 12 female patients, initially aged 2 weeks to 7 months with clinical diagnosis of IP. Standard tests were performed including skin biopsies and ocular, dental and neurologic examinations. Molecular analysis was carried out on 8 out of 12 cases. RESULTS: The initial clinical examination was stage 1 (vesicular lesions), stage 2 (verrucous lesions) or stage 3 (hyperpigmented linear lesions of the trunk/limbs). At the final clinical examination, 10 of our patients had typical vesicular, verrucous or mixed hyper-hypopigmented skin lesions which had persisted from the neonatal period; seven had delayed dentition or conical teeth; two had developmental delay; one had microcephaly and strabismus and two had scarring alopecia. In seven patients, deletion of exons 4-10 of the IKBKG gene was found. In one patient, skewed X-inactivation was demonstrated and a novel mutation p.Gln332X was found. The mothers' DNA analyses were all normal. CONCLUSION: In our sample, all the cases were sporadic and the diagnosis of IP was based mainly on clinical features and confirmed with skin histology. Molecular analysis was used to find the mutations, in some cases to confirm diagnosis and to identify the carriers, which are crucial for prenatal and preimplantation diagnosis. PMID- 20587000 TI - Cyclooxygenase-2/microsomal prostaglandin E synthase-1 complex in the preoptic anterior hypothalamus of the mouse: involvement through fever to intravenous lipopolysaccharide. AB - AIM: Prostaglandin E2 (PGE2) is now well established as a central effector of pyrogen fever. However, questions remain on the source, local vs. blood-borne, of the compound for the early phase of the typically biphasic fever (Phases 1 and 2) to i.v. pyrogens. To verify the role of centrally formed PGE2, we examined the cyclooxygenase (COX)/prostaglandin E synthase (PGES) complex through fever to i.v. lipopolysaccharide (LPS). METHODS: Experiments were carried out in the conscious mouse and LPS effect was ascertained on all steps of expression - gene, protein, catalytic activity - of individual enzymes. The analysis was limited to the preoptic-anterior hypothalamus (AH/POA). RESULTS: We found upregulation of the COX2 transcript together with an upward trend for the mPGES1 transcript during Phase 1. Coincidentally, there was a progressive increase in COX2 and mPGES1 protein expression through Phases 1 and 2. Catalytic activity for COX1 and COX2 combined was instead enhanced only in Phase 2, while mPGES1 activity remained steady at an intrinsically high level. Other COX and PGES enzymes were not modified through either Phase, and COX2/mPGES1 changes subsided with fever defervescence. CONCLUSION: The findings confirm a key function of COX2 and mPGES1 for the synthesis of pyrogenic PGE2 and, at the same time, document their early response to LPS. We conclude that locally formed PGE2 in AH/POA is qualified for a role in the initiation of fever. PMID- 20587001 TI - Preventive health services for systemic lupus erythematosus patients: whose job is it? AB - Apropos of the article about preventive health care for patients with systemic lupus erythematosus in this issue of Arthritis Research & Therapy, we offer some thoughts about how best to delineate the roles of the specialist (rheumatologist) and the generalist in the provision of services to these patients. Even in the best circumstances, these services are now provided at a rate that is less than optimal. We also offer a point about empowering patients to become vigilant about their own care. PMID- 20587002 TI - The role of stress in rheumatic diseases. AB - Rheumatology patients frequently note the occurrence of stressful or traumatic life events prior to the onset of their illness and/or a relationship between stress and disease flares. For our patients, identifying causal events could represent an effort to give meaning to a chronic and often disabling disease, while noting a link between stress and flares may proffer a sense of control. Whatever purpose the report of stress as an etiological or maintaining factor may serve, the science exploring a causal relationship between stress and autoimmune disease onset and course is expanding. Moreover, stress can also induce symptoms such as pain via nonimmunological mechanisms. PMID- 20587003 TI - Clinical proteomics of myeloid leukemia. AB - Myeloid leukemias are a heterogeneous group of diseases originating from bone marrow myeloid progenitor cells. Patients with myeloid leukemias can achieve long term survival through targeted therapy, cure after intensive chemotherapy or short-term survival because of highly chemoresistant disease. Therefore, despite the development of advanced molecular diagnostics, there is an unmet need for efficient therapy that reflects the advanced diagnostics. Although the molecular design of therapeutic agents is aimed at interacting with specific proteins identified through molecular diagnostics, the majority of therapeutic agents act on multiple protein targets. Ongoing studies on the leukemic cell proteome will probably identify a large number of new biomarkers, and the prediction of response to therapy through these markers is an interesting avenue for future personalized medicine. Mass spectrometric protein detection is a fundamental technique in clinical proteomics, and selected tools are presented, including stable isotope labeling with amino acids in cell culture (SILAC), isobaric tags for relative and absolute quantification (iTRAQ) and multiple reaction monitoring (MRM), as well as single cell determination. We suggest that protein analysis will play not only a supplementary, but also a prominent role in future molecular diagnostics, and we outline how accurate knowledge of the molecular therapeutic targets can be used to monitor therapy response. PMID- 20587004 TI - Serotonin transporter polymorphisms and panic disorder. AB - Panic disorder (PD) is the most common anxiety disorder. Although PD seems to occur unprovoked and the underlying etiology is not well understood, studies have consistently shown that genetic factors explain approximately 48% of the variance. Moreover, family and twin studies support the view that the majority of PD cases have a complex genetic basis. Promising findings have most recently implicated the polymorphisms at the 3' end of the serotonin transporter gene SLC6A4 as PD risk variants. If independent studies can replicate the observed association with the SLC6A4 variants and their functional effects on gene expression, this would have a great impact on our understanding of the disease pathophysiology and would provide opportunities to investigate genotype-phenotype correlations. PMID- 20587005 TI - Red cell transfusion triggers in critically ill patients: time for some new TRICCs? AB - Current evidence suggests that critically ill patients tolerate anaemia well and that blood transfusions may increase the risk of adverse outcomes. Dr Sakr and colleagues present a contradictory analysis of a surgical ICU cohort, finding an association between blood transfusions and lower hospital mortality after adjustment for a range of potential confounders. Analyses of this kind are interesting and provocative, but are limited by residual confounding and bias by indication. The data emphasise the need for additional high quality trials of transfusion practice in critical care. PMID- 20587006 TI - Pro: Can biomarkers be gold standards in Alzheimer's disease? AB - Recent advances in biomarkers for Alzheimer's disease (AD) now allow the visualization of one of the hallmark pathologies of AD in vivo, and combination biomarker profiles can now approximate the diagnostic accuracy of autopsy in patients with dementia. Biomarkers are already employed in clinical trials in prodromal AD for both subject selection and in monitoring therapeutic response. Ultimately the greatest utility of biomarkers may be in the preclinical stages of AD, to identify and track progression of the disease prior to significant cognitive impairment, at the point when disease modifying therapies are likely to be most efficacious. PMID- 20587007 TI - Con: Can biomarkers be gold standards in Alzheimer's disease? AB - As Alzheimer's disease remains a clinical diagnosis, and as clinical diagnosis can be difficult, it makes sense to look for so-called biomarkers. A biomarker predicts who is likely to have the illness and who is not. Some biomarkers might even correlate with a clinically meaningful response to treatment. Developing biomarkers is often characterized as searching for a diagnostic gold standard that can seem appealing in its promise of certainty. Even so, considering both the economic history of the gold standard and the results of neuropathological studies, framing the search for measurable, biological correlates of dementia syndromes in this way is likely to be self-defeating. Instead of considering biomarkers as providing certainty through referent criterion validation, currently it makes more sense to test their construct validity and their predictive ability. This means that while biomarkers should inform, they will not dictate clinical meaningfulness. For the foreseeable future, even were they to inform diagnosis, biomarkers cannot substitute for understanding whether patients and caregivers find a given dementia treatment effective. Instead, clinicians should recognize their own determining role, both in dementia diagnosis and in the evaluation of treatment. These roles will best be executed by hearing what patients and caregivers tell us about dementia, and its response to treatment. PMID- 20587008 TI - Ethics roundtable: 'Open-ended ICU care: can we afford it?'. AB - THE CASE: The patient is a 27-year-old previously healthy male with a diagnosis of viral encephalitis with a lymphocytic pleocytosis on cerebrospinal fluid examination. For 3 months, he has been in status epilepticus (SE) on high doses of barbiturates, benzodiazepines, and ketamine and a ketogenic feeding-tube formula. He remains in burst suppression on continuous electroencephalography (EEG). He is trached and has a percutaneous endoscopic gastrostomy (PEG) feeding tube. He has been treated several times for pneumonia, and he is on a warming blanket and is on vasopressors to maintain his blood pressure. His vitals are stable and his lab work is within limits. The sedation is decreased under EEG guidance every 72 hours, after which he goes back into SE and heavy sedation is resumed. The latest magnetic resonance imaging (MRI) shows edema but otherwise no obvious permanent cortical damage. The family wants a realistic assessment of the likely outcome. The neurologist tells them the literature suggests the outlook is poor but not 100% fatal. As long as all of his other organs are functioning on life support, there is always a chance the seizures will stop at some time in the future, and so the neurologist recommends an open-ended intensive care unit (ICU) plan and hopes for that outcome. PMID- 20587009 TI - A hitchhiker's guide to the MADS world of plants. AB - Plant life critically depends on the function of MADS-box genes encoding MADS domain transcription factors, which are present to a limited extent in nearly all major eukaryotic groups, but constitute a large gene family in land plants. There are two types of MADS-box genes, termed type I and type II, and in plants these groups are distinguished by exon-intron and domain structure, rates of evolution, developmental function and degree of functional redundancy. The type I genes are further subdivided into three groups - M alpha, M beta and M gamma - while the type II genes are subdivided into the MIKCC and MIKC* groups. The functional diversification of MIKCC genes is closely linked to the origin of developmental and morphological novelties in the sporophytic (usually diploid) generation of seed plants, most spectacularly the floral organs and fruits of angiosperms. Functional studies suggest different specializations for the different classes of genes; whereas type I genes may preferentially contribute to female gametophyte, embryo and seed development and MIKC*-group genes to male gametophyte development, the MIKCC-group genes became essential for diverse aspects of sporophyte development. Beyond the usual transcriptional regulation, including feedback and feed-forward loops, various specialized mechanisms have evolved to control the expression of MADS-box genes, such as epigenetic control and regulation by small RNAs. In future, more data from genome projects and reverse genetic studies will allow us to understand the birth, functional diversification and death of members of this dynamic and important family of transcription factors in much more detail. PMID- 20587010 TI - Bending the cost curve in the United States: the role of comparative effectiveness research. AB - Owing to an increasing focus on the rising cost of medical care in the United States, bending the cost curve has become the central tenet of healthcare reform. The exact definition of this phrase, however, remains elusive. In order to affect change in the cost and quality of healthcare, the importance of comparative effectiveness research must be recognized. PMID- 20587012 TI - Bidirectional Assessment of Stress, job satisfaction and work ability of Educators in day care centres: a real-time observation study - the study protocol (BASE). AB - BACKGROUND: Occupational demands of educators are not very well researched. Nevertheless their work is subject to several requirements. Whether these demands have an effect on the work ability and the health status of employees has also not been examined. Furthermore it is unclear if the ownership type of day care centres have an influence on job satisfaction and work ability of the pedagogical staff and what kind of resources do exist. Previous studies were mainly based on questionnaire data. Objective data does not exist. Therefore the aim of this investigation is to collect precise data relating to work of educators. METHODS: Effects of different types of ownership of day care centres on job satisfaction and work ability of educators will be assessed with the help of objective real time studies in combination with multi-level psycho diagnostic measurements. DISCUSSION: The present study is the first of its kind. Up to now there are no computer-based real time studies on workflow of pedagogical staff with regard to assess their work-related stress. Following an exhaustive documentation of educators work processes the day-to-day task can be estimated and approaches for prevention can be developed. This can substantially contribute to an overall improvement of child care in Germany. PMID- 20587011 TI - Cancerous stem cells: deviant stem cells with cancer-causing misbehavior. AB - Stem cells maintain homeostasis in adult tissues via self-renewal and generation of terminally differentiated cells. Alterations in this intricate balance can result in disease. It has become increasingly evident that cancer can be initiated at the level of stem cells. Therefore, understanding what causes stem cells to become cancerous may lead to new therapeutic approaches. Multiple signaling pathways ultimately affect stem cell survival and proliferation, thus maintaining homeostasis in the gut. Changes in these pathways could perturb normal stem cell behavior, leading to cancerous stem cells. In addition, cancerous stem cells show resistance to current therapies and may lead to a dangerous selection process resulting in recurrence and metastasis. Genomic instability, the driving force of mutation and resistance, may give cancerous stem cells an adaptive advantage, especially when subjected to cancer therapies. Targeting the unique characteristics of cancerous stem cells to promote either terminal differentiation or destruction would effectively eradicate cancer and improve patient care and survival. PMID- 20587013 TI - Detecting the start of an influenza outbreak using exponentially weighted moving average charts. AB - BACKGROUND: Influenza viruses cause seasonal outbreaks in temperate climates, usually during winter and early spring, and are endemic in tropical climates. The severity and length of influenza outbreaks vary from year to year. Quick and reliable detection of the start of an outbreak is needed to promote public health measures. METHODS: We propose the use of an exponentially weighted moving average (EWMA) control chart of laboratory confirmed influenza counts to detect the start and end of influenza outbreaks. RESULTS: The chart is shown to provide timely signals in an example application with seven years of data from Victoria, Australia. CONCLUSIONS: The EWMA control chart could be applied in other applications to quickly detect influenza outbreaks. PMID- 20587014 TI - Co-occurrence of outlet impingement syndrome of the shoulder and restricted range of motion in the thoracic spine--a prospective study with ultrasound-based motion analysis. AB - BACKGROUND: Shoulder complaints, and especially the outlet-impingement syndrome, are a common condition. Among other things, poor posture has been discussed as a cause. A correlation between impingement syndrome and restricted mobility of the thoracic spine (T) has been described earlier, but there has been no motion analysis of the thoracic spine to show these correlations. In the present prospective study, we intended to find out whether there is a significant difference in the thoracic sagittal range of motion (ROM) between patients with a shoulder outlet impingement syndrome and a group of patients who had no shoulder pathology. Secondly, we wanted to clarify whether Ott's sign correlates with ultrasound topometric measurements. METHODS: Two sex- and age-matched groups (2 x n = 39) underwent a clinical and an ultrasound topometric examination. The postures examined were sitting up straight, sitting in maximal flexion and sitting in maximal extension. The disabilities of the arm, shoulder and hand (DASH) score (obtained by means of a self-assessment questionnaire) and the Constant score were calculated. Lengthening and shortening of the dorsal projections of the spine in functional positions was measured by tape with Ott's sign. RESULTS: On examination of the thoracic kyphosis in the erect seated posture there were no significant differences between the two groups (p = 0.66). With ultrasound topometric measurement it was possible to show a significantly restricted segmental mobility of the thoracic spine in the study group compared with the control group (p = 0.01). An in-depth look at the mobility of the subsegments T1-4, T5-8 and T9-12 revealed that differences between the groups in the mobility in the lower two sections of the thoracic spine were significant (T5 8: p = 0.03; T9-12: p = 0.02). The study group had an average Constant score of 35.1 points and the control group, 85.5 (p < 0.001). On the DASH score the patient group reached 34.2 points and the control group, 1.4 (p < 0.001). The results of Ott's sign differed significantly between the two collectives (p = 0.0018), but showed a weak correlation with the ultrasound topometric measurements (study group flexion/extension: r = 0.36/0.43, control group flexion/extension: r = 0.29/0.26). CONCLUSION: The mobility of the thoracic spine should receive more attention in the diagnosis and therapy of patients with shoulder outlet impingement syndrome. PMID- 20587015 TI - Bumblebee foraging rhythms under the midnight sun measured with radiofrequency identification. AB - BACKGROUND: In the permanent daylight conditions north of the Arctic circle, there is a unique opportunity for bumblebee foragers to maximise intake, and therefore colony growth, by remaining active during the entire available 24-h period. We tested the foraging rhythms of bumblebee (Bombus terrestris and B. pascuorum) colonies in northern Finland during the summer, when the sun stays above the horizon for weeks. We used fully automatic radio-frequency identification to monitor the foraging activity of more than 1,000 workers and analysed their circadian foraging rhythms. RESULTS: Foragers did not use the available 24-h foraging period but exhibited robust diurnal rhythms instead. A mean of 95.2% of the tested B. terrestris workers showed robust diurnal rhythms with a mean period of 23.8 h. Foraging activity took place mainly between 08:00 and 23:00, with only low or almost no activity during the rest of the day. Activity levels increased steadily during the morning, reached a maximum around midday and decreased again during late afternoon and early evening. Foraging patterns of native B. pascuorum followed the same temporal organisation, with the foraging activity being restricted to the period between 06:00 and 22:00. CONCLUSIONS: The results of the present study indicate that the circadian clock of the foragers must have been entrained by some external cue, the most prominent being daily cycles in light intensity and temperature. Daily fluctuations in the spectral composition of light, especially in the UV range, could also be responsible for synchronising the circadian clock of the foragers under continuous daylight conditions. PMID- 20587016 TI - Capacity development for health research in Africa: experiences managing the African Doctoral Dissertation Research Fellowship Program. AB - Africa's progress depends on her capacity to generate, adapt, and use scientific knowledge to meet regional health and development needs. Yet, Africa's higher education institutions that are mandated to foster this capacity lack adequate resources to generate and apply knowledge, raising the need for innovative approaches to enhance research capacity. In this paper, we describe a newly developed program to support PhD research in health and population sciences at African universities, the African Doctoral Dissertation Research Fellowship (ADDRF) Program. We also share our experiences implementing the program. As health research capacity-strengthening in Africa continues to attract attention and as the need for such programs to be African-led is emphasized, our experiences in developing and implementing the ADDRF offer invaluable lessons to other institutions undertaking similar initiatives. PMID- 20587017 TI - Predator-induced defences in Daphnia pulex: selection and evaluation of internal reference genes for gene expression studies with real-time PCR. AB - BACKGROUND: The planktonic microcrustacean Daphnia pulex is among the best studied animals in ecological, toxicological and evolutionary research. One aspect that has sustained interest in the study system is the ability of D. pulex to develop inducible defence structures when exposed to predators, such as the phantom midge larvae Chaoborus. The available draft genome sequence for D. pulex is accelerating research to identify genes that confer plastic phenotypes that are regularly cued by environmental stimuli. Yet for quantifying gene expression levels, no experimentally validated set of internal control genes exists for the accurate normalization of qRT-PCR data. RESULTS: In this study, we tested six candidate reference genes for normalizing transcription levels of D. pulex genes; alpha tubulin (aTub), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), TATA box binding protein (Tbp) syntaxin 16 (Stx16), X-box binding protein 1 (Xbp1) and CAPON, a protein associated with the neuronal nitric oxide synthase, were selected on the basis of an earlier study and from microarray studies. One additional gene, a matrix metalloproteinase (MMP), was tested to validate its transcriptional response to Chaoborus, which was earlier observed in a microarray study. The transcription profiles of these seven genes were assessed by qRT-PCR from RNA of juvenile D. pulex that showed induced defences in comparison to untreated control animals. We tested the individual suitability of genes for expression normalization using the programs geNorm, NormFinder and BestKeeper. Intriguingly, Xbp1, Tbp, CAPON and Stx16 were selected as ideal reference genes. Analyses on the relative expression level using the software REST showed that both classical housekeeping candidate genes (aTub and GAPDH) were significantly downregulated, whereas the MMP gene was shown to be significantly upregulated, as predicted. aTub is a particularly ill suited reference gene because five copies are found in the D. pulex genome sequence. When applying aTub for expression normalization Xbp1 and Tbp are falsely reported as significantly upregulated. CONCLUSIONS: Our results suggest that the genes Xbp1, Tbp, CAPON and Stx16 are suitable reference genes for accurate normalization in qRT-PCR studies using Chaoborus-induced D. pulex specimens. Furthermore, our study underscores the importance of verifying the expression stability of putative reference genes for normalization of expression levels. PMID- 20587018 TI - Hertfordshire sarcopenia study: design and methods. AB - BACKGROUND: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms. METHODS: One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study. DISCUSSION: The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia. PMID- 20587019 TI - First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial. AB - BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics. PMID- 20587020 TI - A qualitative analysis of immigrant population health practices in the Girona Healthcare Region. AB - BACKGROUND: The research we present here forms part of a two-phase project - one quantitative and the other qualitative - assessing the use of primary health care services. This paper presents the qualitative phase of said research, which is aimed at ascertaining the needs, beliefs, barriers to access and health practices of the immigrant population in comparison with the native population, as well as the perceptions of healthcare professionals. Moroccan and sub-Saharan were the immigrants to who the qualitative phase was specifically addressed. The aims of this paper are as follows: to analyse any possible implications of family organisation in the health practices of the immigrant population; to ascertain social practices relating to illness; to understand the significances of sexual and reproductive health practices; and to ascertain the ideas and perceptions of immigrants, local people and professionals regarding health and the health system. METHODS: Qualitative research based on discursive analysis. Data gathering techniques consisted of discussion groups with health system users and semi-structured individual interviews with healthcare professionals. The sample was taken from the Basic Healthcare Areas of Salt and Banyoles (belonging to the Girona Healthcare Region), the discussion groups being comprised of (a) 6 immigrant Moroccan women, (b) 7 immigrant sub-Saharan African women and (c) 6 immigrant and native population men (2 native men, 2 Moroccan men and 2 sub Saharan men); and the semi-structured interviews being conducted with the following healthcare professionals: (a) 3 gynaecologists, (b) 3 nurses and 1 administrative staff. RESULTS: Use of the healthcare system is linked to the perception of not being well, knowledge of the healthcare system, length of time resident in Spain and interiorization of traditional Western medicine as a cure mechanism. The divergences found among the groups of immigrants, local people and healthcare professionals with regard to healthcare education, use of the healthcare service, sexual and reproductive healthcare and reticence with regard to being attended by healthcare personnel of the opposite sex demonstrate a need to work with the immigrant population as a heterogeneous group. CONCLUSIONS: The results we have obtained support the idea that feeling unwell is a psycho-social process, as it takes place within a specific socio-cultural situation and spans a range of beliefs, perceptions and ideas regarding symptomology and how to treat it. PMID- 20587021 TI - Healthcare professionals' intentions to use clinical guidelines: a survey using the theory of planned behaviour. AB - BACKGROUND: Finnish clinical guidelines are evolving toward integration of knowledge modules into the electronic health record in the Evidence-Based Medicine electronic Decision Support project. It therefore became important to study which factors affect professionals' intention to use clinical guidelines generally in their decision-making on patient care. A theory-based approach is a possible solution to explore determinants of professionals' behaviour. The study's aim was to produce baseline information for developers and implementers by using the theory of planned behaviour. METHODS: A cross-sectional internet based survey was carried out in Finnish healthcare organisations within three hospital districts. The target population (n = 2,252) included physicians, nurses, and other professionals, of whom 806 participated. Indicators of the intention to use clinical guidelines were observed by using a theory-based questionnaire. The main data analysis was done by means of multiple linear regressions. RESULTS: The results indicated that all theory-based variables--the attitude toward the behaviour, the subjective norm, and the perceived behaviour control--were important factors associated with the professionals' intention to use clinical practice guidelines for their area of specialisation in the decisions they would make on the care of patients in the next three months. In addition, both the nurse and the physician factors had positive (p < 0.01) effects on this intention in comparison to other professionals. In the similar models for all professions, the strongest factor for the physicians was the perceived behaviour control, while the key factor for the nurses and the other professionals was the subjective norm. This means that context- and guideline based factors either facilitate or hinder the intention to use clinical guidelines among physicians and, correspondingly, normative beliefs related to social pressures do so for nurses and other healthcare professionals. CONCLUSIONS: The results confirm suggestions that the theory of planned behaviour is a suitable theoretical basis for implementing clinical guidelines in healthcare practices. Our new finding was that, in general, profession had an effect on intention to use clinical guidelines in patient care. Therefore, the study reaffirms the general contention that different strategies need to be in place when clinical guidelines are targeted at different professional groups. PMID- 20587022 TI - Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation by Sp1. AB - BACKGROUND: Activin receptor-like kinase 1 (ALK1) is a Transforming Growth Factor beta (TGF-beta) receptor type I, mainly expressed in endothelial cells that plays a pivotal role in vascular remodelling and angiogenesis. Mutations in the ALK1 gene (ACVRL1) give rise to Hereditary Haemorrhagic Telangiectasia, a dominant autosomal vascular dysplasia caused by a haploinsufficiency mechanism. In spite of its patho-physiological relevance, little is known about the transcriptional regulation of ACVRL1. Here, we have studied the different origins of ACVRL1 transcription, we have analyzed in silico its 5'-proximal promoter sequence and we have characterized the role of Sp1 in the transcriptional regulation of ACVRL1. RESULTS: We have performed a 5'Rapid Amplification of cDNA Ends (5'RACE) of ACVRL1 transcripts, finding two new transcriptional origins, upstream of the one previously described, that give rise to a new exon undiscovered to date. The 5'-proximal promoter region of ACVRL1 (-1,035/+210) was analyzed in silico, finding that it lacks TATA/CAAT boxes, but contains a remarkably high number of GC-rich Sp1 consensus sites. In cells lacking Sp1, ACVRL1 promoter reporters did not present any significant transcriptional activity, whereas increasing concentrations of Sp1 triggered a dose-dependent stimulation of its transcription. Moreover, silencing Sp1 in HEK293T cells resulted in a marked decrease of ACVRL1 transcriptional activity. Chromatin immunoprecipitation assays demonstrated multiple Sp1 binding sites along the proximal promoter region of ACVRL1 in endothelial cells. Furthermore, demethylation of CpG islands, led to an increase in ACVRL1 transcription, whereas in vitro hypermethylation resulted in the abolishment of Sp1-dependent transcriptional activation of ACVRL1. CONCLUSIONS: Our results describe two new transcriptional start sites in ACVRL1 gene, and indicate that Sp1 is a key regulator of ACVRL1 transcription, providing new insights into the molecular mechanisms that contribute to the expression of ACVRL1 gene. Moreover, our data show that the methylation status of CpG islands markedly modulates the Sp1 regulation of ACVRL1 gene transcriptional activity. PMID- 20587023 TI - Solitary colonic metastasis from renal cell carcinoma presenting as a surgical emergency nine years post-nephrectomy. AB - Late colonic metastasis following curative surgery for renal cell carcinoma has rarely been described. We present the first reported case of solitary colonic renal cell carcinoma metastasis presenting as an intra-abdominal bleed, nine years post-nephrectomy. PMID- 20587024 TI - BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. AB - BACKGROUND: Quantitative models of biochemical and cellular systems are used to answer a variety of questions in the biological sciences. The number of published quantitative models is growing steadily thanks to increasing interest in the use of models as well as the development of improved software systems and the availability of better, cheaper computer hardware. To maximise the benefits of this growing body of models, the field needs centralised model repositories that will encourage, facilitate and promote model dissemination and reuse. Ideally, the models stored in these repositories should be extensively tested and encoded in community-supported and standardised formats. In addition, the models and their components should be cross-referenced with other resources in order to allow their unambiguous identification. DESCRIPTION: BioModels Database http://www.ebi.ac.uk/biomodels/ is aimed at addressing exactly these needs. It is a freely-accessible online resource for storing, viewing, retrieving, and analysing published, peer-reviewed quantitative models of biochemical and cellular systems. The structure and behaviour of each simulation model distributed by BioModels Database are thoroughly checked; in addition, model elements are annotated with terms from controlled vocabularies as well as linked to relevant data resources. Models can be examined online or downloaded in various formats. Reaction network diagrams generated from the models are also available in several formats. BioModels Database also provides features such as online simulation and the extraction of components from large scale models into smaller submodels. Finally, the system provides a range of web services that external software systems can use to access up-to-date data from the database. CONCLUSIONS: BioModels Database has become a recognised reference resource for systems biology. It is being used by the community in a variety of ways; for example, it is used to benchmark different simulation systems, and to study the clustering of models based upon their annotations. Model deposition to the database today is advised by several publishers of scientific journals. The models in BioModels Database are freely distributed and reusable; the underlying software infrastructure is also available from SourceForge https://sourceforge.net/projects/biomodels/ under the GNU General Public License. PMID- 20587025 TI - Characterisation of the sarcomeric myosin heavy chain multigene family in the laboratory guinea pig. AB - BACKGROUND: Several chronic conditions leading to skeletal muscle dysfunction are known to be associated with changes in the expression of myosin heavy chain (MHC) isoforms at both the mRNA and protein level. Many of these conditions are modelled, pre-clinically, in the guinea pig due to similar disease onset and progression to the human condition, and their generally well-characterised anatomy. MHC composition is amenable to determination by protein and mRNA based methodologies, the latter quantifying the expression of MHC isoform-specific gene transcripts allowing the detection of earlier, and more subtle changes. As such, the MHC mRNAs, and specific oligonucleotide primers of all common laboratory species have been available for some time. However, due to incomplete genomic annotation, assessment of guinea pig MHC mRNA expression has not been previously possible, precluding the full characterisation of early changes in skeletal muscle in response to disease and disease modulation.The purpose of this study was to characterise the multigenic structure of the sarcomeric MHC family in the guinea pig, and to design and validate specific oligonucleotide primers to enable the assessment of the predominant adult-muscle associated MHC mRNAs in relevant disease models. RESULTS: Using a combination of ligase-mediated rapid amplification of 5' and 3' cDNA ends (RACE) and bioinformatics, mRNAs to the four main skeletal-muscle isoforms of MHC were determined. Specific oligonucleotide primers were designed, and following verification of their specificity, found to successfully determine the expression of each MHC mRNA independently. CONCLUSIONS: Because of their utilisation in the in vivo modelling of disease, there is a requirement to develop molecular methods that accurately differentiate the different MHC mRNAs in the guinea pig to enable rapid profiling of muscle composition in appropriate disease models. The methods developed here are suitable for the characterisation of muscle MHC expression at the molecular level from animal tissue samples and biopsy material. The publication of these specific oligonucleotide primers for the guinea pig MHC variants will enable researchers to rapidly and accurately quantify acute changes in MHC mRNA expression in either developmental or in guinea pig disease models where a marker of altered skeletal muscle function is required. PMID- 20587026 TI - Verbal autopsy interpretation: a comparative analysis of the InterVA model versus physician review in determining causes of death in the Nairobi DSS. AB - BACKGROUND: Developing countries generally lack complete vital registration systems that can produce cause of death information for health planning in their populations. As an alternative, verbal autopsy (VA) - the process of interviewing family members or caregivers on the circumstances leading to death - is often used by Demographic Surveillance Systems to generate cause of death data. Physician review (PR) is the most common method of interpreting VA, but this method is a time- and resource-intensive process and is liable to produce inconsistent results. The aim of this paper is to explore how a computer-based probabilistic model, InterVA, performs in comparison with PR in interpreting VA data in the Nairobi Urban Health and Demographic Surveillance System (NUHDSS). METHODS: Between August 2002 and December 2008, a total of 1,823 VA interviews were reviewed by physicians in the NUHDSS. Data on these interviews were entered into the InterVA model for interpretation. Cause-specific mortality fractions were then derived from the cause of death data generated by the physicians and by the model. We then estimated the level of agreement between both methods using Kappa statistics. RESULTS: The level of agreement between individual causes of death assigned by both methods was only 35% (kappa = 0.27, 95% CI: 0.25 - 0.30). However, the patterns of mortality as determined by both methods showed a high burden of infectious diseases, including HIV/AIDS, tuberculosis, and pneumonia, in the study population. These mortality patterns are consistent with existing knowledge on the burden of disease in underdeveloped communities in Africa. CONCLUSIONS: The InterVA model showed promising results as a community-level tool for generating cause of death data from VAs. We recommend further refinement to the model, its adaptation to suit local contexts, and its continued validation with more extensive data from different settings. PMID- 20587027 TI - A putative lytic transglycosylase tightly regulated and critical for the EHEC type three secretion. AB - Open reading frame l0045 in the pathogenic island of enterohemorrhagic Escherichia coli O157:H7 has been predicted to encode a lytic transglycosylase that is homologous to two different gene products encoded by the same bacteria at loci away from the island. To deduce the necessity of the presence in the island, we created an l0045-deleted strain of EHEC and observed that both the level of cytosolic EspA and that of the other type III secreted proteins in the media were affected. In a complementation assay, a low level-expressing L0045 appeared to recover efficiently the type III secretion (TTS). On the other hand, when l0045 was driven to express robustly, the intracellular levels of representative TTS proteins were severely suppressed. This suppression is apparently caused by the protein of L0045 per se since introducing an early translational termination codon abolished the suppression. Intriguingly, the authentic L0045 was hardly detected in all lysates of EHEC differently prepared while the same construct was expectedly expressed in the K-12 strain. A unique network must exist in EHEC to tightly regulate the presence of L0045, and we found that a LEE regulator (GrlA) is critically involved in this regulation. PMID- 20587028 TI - Reduced acquisition and reactivation of human papillomavirus infections among older women treated with cryotherapy: results from a randomized trial in South Africa. AB - BACKGROUND: Treatment of women for high-grade cervical cancer precursors frequently results in clearance of the associated high-risk human papillomavirus (hrHPV) infection but the role of treatment among women without hrHPV is unknown. We investigated whether cervical cryotherapy reduces newly detected hrHPV infections among HIV-positive and HIV-negative women who were hrHPV negative when treated. METHODS: The impact of cryotherapy on newly detected hrHPV infections was examined among 612 women of known HIV serostatus, aged 35 to 65 years, who were negative for hrHPV DNA, and randomized to either undergo cryotherapy (n = 309) or not (n = 303). All women underwent repeat hrHPV DNA testing 6, 12, 24, and 36 months later. RESULTS: Among 540 HIV-negative women, cryotherapy was associated with a significant reduction in newly detected hrHPV infections. Women in the cryotherapy group were 55% less likely to have newly detected hrHPV than women in the control group (95% CI 0.28 to 0.71). This association was independent of the influence of changes in sexual behaviors following therapy (adjusted hazards ratio (HR) = 0.49, 95% CI 0.29 to 0.81). Among 72 HIV-positive women, similar reductions were not observed (HR = 1.10, 95% CI 0.53 to 2.29). CONCLUSIONS: Cervical cryotherapy significantly reduced newly detected hrHPV infections among HIV-negative, but not HIV-positive women. These results raise intriguing questions about immunological responses and biological mechanisms underlying the apparent prophylactic benefits of cryotherapy. PMID- 20587029 TI - Inference of sparse combinatorial-control networks from gene-expression data: a message passing approach. AB - BACKGROUND: Transcriptional gene regulation is one of the most important mechanisms in controlling many essential cellular processes, including cell development, cell-cycle control, and the cellular response to variations in environmental conditions. Genes are regulated by transcription factors and other genes/proteins via a complex interconnection network. Such regulatory links may be predicted using microarray expression data, but most regulation models suppose transcription factor independence, which leads to spurious links when many genes have highly correlated expression levels. RESULTS: We propose a new algorithm to infer combinatorial control networks from gene-expression data. Based on a simple model of combinatorial gene regulation, it includes a message-passing approach which avoids explicit sampling over putative gene-regulatory networks. This algorithm is shown to recover the structure of a simple artificial cell-cycle network model for baker's yeast. It is then applied to a large-scale yeast gene expression dataset in order to identify combinatorial regulations, and to a data set of direct medical interest, namely the Pleiotropic Drug Resistance (PDR) network. CONCLUSIONS: The algorithm we designed is able to recover biologically meaningful interactions, as shown by recent experimental results 1. Moreover, new cases of combinatorial control are predicted, showing how simple models taking this phenomenon into account can lead to informative predictions and allow to extract more putative regulatory interactions from microarray databases. PMID- 20587030 TI - Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2. AB - BACKGROUND: Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer. METHODS: Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE). RESULTS: Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot. CONCLUSIONS: These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer. PMID- 20587031 TI - Differentiating Plasmodium falciparum alleles by transforming Cartesian X,Y data to polar coordinates. AB - BACKGROUND: Diagnosis of infectious diseases now benefits from advancing technology to perform multiplex analysis of a growing number of variables. These advances enable simultaneous surveillance of markers characterizing species and strain complexity, mutations associated with drug susceptibility, and antigen based polymorphisms in relation to evaluation of vaccine effectiveness. We have recently developed assays detecting single nucleotide polymorphisms (SNPs) in the P. falciparum genome that take advantage of post-PCR ligation detection reaction and fluorescent microsphere labeling strategies. Data from these assays produce a spectrum of outcomes showing that infections result from single to multiple strains. Traditional methods for distinguishing true positive signal from background can cause false positive diagnoses leading to incorrect interpretation of outcomes associated with disease treatment. RESULTS: Following analysis of Plasmodium falciparum dihydrofolate reductase SNPs associated with resistance to a commonly used antimalarial drug, Fansidar (Sulfadoxine/pyrimethamine), and presumably neutral SNPs for parasite strain differentiation, we first evaluated our data after setting a background signal based on the mean plus three standard deviations for known negative control samples. Our analysis of single allelic controls suggested that background for the absent allele increased as the concentration of the target allele increased. To address this problem, we introduced a simple change of variables from customary (X,Y) (Cartesian) coordinates to planar polar coordinates (X = rcos(theta), Y = rsin(theta)). Classification of multidimensional fluorescence signals based on histograms of angular and radial data distributions proved more effective than classification based on Cartesian thresholds. Comparison with known diallelic dilution controls suggests that histogram-based classification is effective for major:minor allele concentration ratios as high as 10:1. CONCLUSION: We have observed that the diallelic SNP data resulting from analysis of P. falciparum mutations is more accurately diagnosed when a simple polar transform of the (X,Y) data into (r,theta) is used. The development of high through-put methods for genotyping P. falciparum SNPs and the refinement of analytical approaches for evaluating these molecular diagnostic results significantly advance the evaluation of parasite population diversity and antimalarial drug resistance. PMID- 20587032 TI - BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis. AB - BACKGROUND: Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette Guerin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC). We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. RESULTS: In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4 Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. CONCLUSIONS: S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC. PMID- 20587033 TI - Yeast karyopherin Kap95 is required for cell cycle progression at Start. AB - BACKGROUND: The control of the subcellular localization of cell cycle regulators has emerged as a crucial mechanism in cell division regulation. The active transport of proteins between the nucleus and the cytoplasm is mediated by the transport receptors of the beta-karyopherin family. In this work we characterized the terminal phenotype of a mutant strain in beta-karyopherin Kap95, a component of the classical nuclear import pathway. RESULTS: When KAP95 was inactivated, most cells arrested at the G2/M phase of the cell cycle, which is in agreement with the results observed in mutants in the other components of this pathway. However, a number of cells accumulate at G1, suggesting a novel role of Kap95 and the classical import pathway at Start. We investigated the localization of Start transcription factors. It is known that Swi6 contains a classical NLS that interacts with importin alpha. Here we show that the in vivo nuclear import of Swi6 depends on Kap95. For Swi4, we identified a functional NLS between amino acids 371 and 376 that is sufficient and necessary for Swi4 to enter the nucleus. The nuclear import driven by this NLS is mediated by karyopherins Kap95 and Srp1. Inactivation of Kap95 also produces a dramatic change in the localization of Mbp1 since the protein is mainly detected in the cytoplasm. Two functionally redundant Kap95- and Srp1-dependent NLSs were identified in Mbp1 between amino acids 27-30 and 166-181. Nuclear accumulation was not completely abolished in a kap95 mutant or in the Mbp1 mutated in the two NLSs, suggesting that alternative pathways might contribute to the Mbp1 nuclear import to a lesser extent. CONCLUSIONS: Kap95 plays an essential role at the initiation of the cell cycle by driving the nuclear import of Swi4, Swi6 and Mbp1, the three transcription factors responsible for the gene expression at Start. This transport depends on the specific nuclear localization signals present in cargo proteins. PMID- 20587034 TI - Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation. AB - BACKGROUND: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs. METHODS: Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls. RESULTS: Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 +/- 0.01, mean +/- SEM) and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 +/- 0.2 vs 6.1 +/- 0.8, mmHg/ml, p < 0.001) and end-systolic elastance to effective arterial elastance ratio (0.6 +/- 0.1 vs 1.4 +/- 0.2, p < 0.001), with altered active relaxation (dP/dtmin -1992 +/- 71 vs -2821 +/- 305, mmHg/s, p < 0.01) but preserved left ventricular capacitance (70 +/- 6 vs 61 +/- 3, ml at 20 mmHg, p = NS) and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin. CONCLUSIONS: In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function. PMID- 20587035 TI - Development of clinically relevant orthotopic xenograft mouse model of metastatic lung cancer and glioblastoma through surgical tumor tissues injection with trocar. AB - OBJECTIVE: Orthotopic models are important in cancer research. Here we developed orthotopic xenograft mouse model of metastatic lung cancer and glioblastoma with a specially designed system. METHODS: Tiny fragments of surgical tumors were implanted into the mice brain with a trocar system. Immunohistochemistry was performed to detect brain tumor stem cells among glioblastoma tissues, including both the original and resulting ones with monoclonal antibody against CD133. RESULTS: Besides the constant high take rates in both models; brain transplants perfectly resembled their original tumors in biological behaviors. The brain tumor stem cells, positively stained with CD133 were found, though not frequently, in both original and resulting glioblastoma tissues. CONCLUSIONS: Orthotopic model established with a trocar system is effective and injection of tumor tissues containing stem cells promise the forming of new tumor mass when grafted. PMID- 20587036 TI - Impact of the Family Health Program on the quality of vital information and reduction of child unattended deaths in Brazil: an ecological longitudinal study. AB - BACKGROUND: Vital information, despite of being an important public health instrument for planning and evaluation, in most of the developing countries have still low quality and coverage. Brazil has recently implemented the Family Health Program (PSF), one of the largest comprehensive primary health care programs in the world, which demonstrated effectiveness on the reduction of infant mortality. In the present study we evaluate the impact of the PSF on mortality rates related to the quality of vital information: the under-five mortality rate due to ill defined causes and unattended death. METHODS: Data on mortality rates and PSF coverage was obtained for the total 5,507 Brazilian municipalities from 2000 to 2006. A multivariate regression analysis of panel data was carried out with a negative binomial response by using fixed effects models that control for relevant covariates. RESULTS: A statistically significant negative association was observed between PSF coverage levels, classified in none (0%, the reference category), low (<30.0%), intermediate (>or= 30.0% and <70.0%) and high (>or= 70.0%), and all analysed mortalities rates, with a reduction of 17% (Rate Ratio [RR]: 0.83; 95% confidence interval [CI]: 0.79 - 0.88), 35% (RR: 0.65; 95% CI: 0.61-0.68) and 50% (RR: 0.50; 95% CI: 0.47-0.53) on under-five mortality due to ill-defined causes, respectively. In the mortality rate for unattended death the reduction was even greater, reaching 60% (RR: 0.40; 95% CI: 0.37-0.44) in the municipalities with the highest PSF coverage. The PSF effect on unattended deaths was slightly stronger in municipalities with a higher human development index. CONCLUSIONS: The PSF, a primary health care program developed mostly in rural and deprived areas, had an important role on reducing the unattended deaths and improving the quality of vital information in Brazil. PMID- 20587037 TI - Lighting during grow-out and Salmonella in broiler flocks. AB - BACKGROUND: Lighting is used during conventional broiler grow-out to modify bird behaviour to reach the goals of production and improve bird welfare. The protocols for lighting intensity vary. In a field study, we evaluated if the lighting practices impact the burden of Salmonella in broiler flocks. METHODS: Conventional grow-out flocks reared in the states of Alabama, Mississippi and Texas, USA in 2003 to 2006 were sampled 1 week before harvest (n = 58) and upon arrival for processing (n = 56) by collecting feathered carcass rinsate, crop and one cecum from each of 30 birds, and during processing by collecting rinsate of 30 carcasses at pre-chilling (n = 56) and post-chilling points (n = 54). Litter samples and drag swabs of litter were collected from the grow-out houses after bird harvest (n = 56). Lighting practices for these flocks were obtained with a questionnaire completed by the growers. Associations between the lighting practices and the burden of Salmonella in the flocks were tested while accounting for variation between the grow-out farms, their production complexes and companies. RESULTS: Longer relative duration of reduced lights during the grow out period was associated with reduced detection of Salmonella on the exterior of birds 1 week before harvest and on the broiler carcasses at the post-chilling point of processing. In addition, starting reduced lights for > or = 18 hours per day later in the grow-out period was associated with decreased detection of Salmonella on the exterior of broilers arriving for processing and in the post harvest drag swabs of litter from the grow-out house. CONCLUSIONS: The results of this field study show that lighting practices implemented during broiler rearing can impact the burden of Salmonella in the flock. The underlying mechanisms are likely to be interactive. PMID- 20587038 TI - Supplementation of diet with krill oil protects against experimental rheumatoid arthritis. AB - BACKGROUND: Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis. METHODS: Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1alpha, IL 1beta, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-beta were determined by a Luminex assay system. RESULTS: Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1alpha and IL-13. CONCLUSIONS: The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis. PMID- 20587040 TI - Potentially fatal new trend in performance enhancement: a cautionary note on nitrite. AB - BACKGROUND: Considerable interest has been shown by athletes and scientists in the potential for nitric oxide and associated vasodilators to enhance performance. This study aims to explore potential misuse of vasodilators by the athletes, and to highlight the growing concern over these agents. METHODS: Retrospective analyses of anonymous inquiries recorded in the Drug Information Database (DID) between January 2006 and June 2008 (inclusive). In this 30-month period, the DID recorded 198,023 inquiries, of which 118,724 were UK Licensed Pharmaceutical products with a further 79,299 inquiries made for substance not found in the database. RESULTS: Phosphodiesterase type 5 (PDE-5) inhibitors, dominated by Viagra(R), ranked 16th among the substance groups. The proportion of the inquiries made regarding PDE-5 inhibitors, especially in comparison to antibiotics, painkillers or alcohol, appears to be above the level that would normally be expected from medical need. No significant change in the months leading up to the Beijing Olympics was observed. On the contrary, the Nitric/Nitrate group showed a notable increase between 2006-2007 and 2008, suggesting a potential increase in interest in using nitric oxide among athletes. CONCLUSIONS: With patents recently filed for the use of agents containing sodium nitrite/nitrate to enhance blood flow for performance enhancement in sport, coupled with anecdotal evidence from internet athlete forums and media, there is a concern that athletes may endanger their health by using vasodilators to enhance athletic performance. PDE-5 inhibitors or chemicals in the nitrate/nitrate group are currently not prohibited or tested for by the doping control agencies but some are highly dangerous to health and can lead to cardiovascular collapse, coma and death. Its promotion among athletes as a performance enhancing supplement is ethically and medically questionable. PMID- 20587039 TI - Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency. AB - BACKGROUND: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency. METHODS: We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study. RESULTS: An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles. CONCLUSIONS: This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying CYP21A1P/A2 chimeric genes in Brazil. PMID- 20587041 TI - Comparing large-scale computational approaches to epidemic modeling: agent-based versus structured metapopulation models. AB - BACKGROUND: In recent years large-scale computational models for the realistic simulation of epidemic outbreaks have been used with increased frequency. Methodologies adapt to the scale of interest and range from very detailed agent based models to spatially-structured metapopulation models. One major issue thus concerns to what extent the geotemporal spreading pattern found by different modeling approaches may differ and depend on the different approximations and assumptions used. METHODS: We provide for the first time a side-by-side comparison of the results obtained with a stochastic agent-based model and a structured metapopulation stochastic model for the progression of a baseline pandemic event in Italy, a large and geographically heterogeneous European country. The agent-based model is based on the explicit representation of the Italian population through highly detailed data on the socio-demographic structure. The metapopulation simulations use the GLobal Epidemic and Mobility (GLEaM) model, based on high-resolution census data worldwide, and integrating airline travel flow data with short-range human mobility patterns at the global scale. The model also considers age structure data for Italy. GLEaM and the agent based models are synchronized in their initial conditions by using the same disease parameterization, and by defining the same importation of infected cases from international travels. RESULTS: The results obtained show that both models provide epidemic patterns that are in very good agreement at the granularity levels accessible by both approaches, with differences in peak timing on the order of a few days. The relative difference of the epidemic size depends on the basic reproductive ratio, R0, and on the fact that the metapopulation model consistently yields a larger incidence than the agent-based model, as expected due to the differences in the structure in the intra-population contact pattern of the approaches. The age breakdown analysis shows that similar attack rates are obtained for the younger age classes. CONCLUSIONS: The good agreement between the two modeling approaches is very important for defining the tradeoff between data availability and the information provided by the models. The results we present define the possibility of hybrid models combining the agent-based and the metapopulation approaches according to the available data and computational resources. PMID- 20587043 TI - The effectiveness of educational practice in diabetic foot: a view from Brazil. AB - BACKGROUND: The aim of the present study was to evaluate the prevention and self inspection behavior of diabetic subjects with foot at ulcer risk, no previous episode, who participated in the routine visits and standardized education provided by the service and who received prescribed footwear. This evaluation was carried out using a questionnaire scoring from 0-10 (high scores reflect worse practice compliance). RESULTS: 60 patients were studied (30 of each sex); mean age was 62 years, mean duration of the disease was 17 years. As for compliance, 90% showed a total score 25.3%) performed better than both Moran's I (> 24.6%) and I*pop (> 7.9%) with the adjacent weight function. With the population density weight function, all methods performed equally well.In the real data example, all statistics indicate the existence of a global clustering pattern in a leukemia data set. The modified Moran's I has the lowest p-value (.0014) followed by Moran's I (.0156) and I*pop (.011). CONCLUSIONS: Our power analysis and simulation study show that the modified Moran's I achieved higher power than Moran's I and I*pop for evaluating global and local clustering patterns on geographic data with homogeneous populations. The inclusion of the PD weight function which in turn redefines the neighbors seems to have a large impact on the power of detecting global clustering patterns. Our methods to improve the original version of Moran's I for homogeneous populations can also be extended to some alternative versions of Moran's I methods developed for heterogeneous populations. PMID- 20587046 TI - Demarcation of local neighborhoods to study relations between contextual factors and health. AB - BACKGROUND: Several studies have highlighted the importance of collective social factors for population health. One of the major challenges is an adequate definition of the spatial units of analysis which present properties potentially related to the target outcomes. Political and administrative divisions of urban areas are the most commonly used definition, although they suffer limitations in their ability to fully express the neighborhoods as social and spatial units. OBJECTIVE: This study presents a proposal for defining the boundaries of local neighborhoods in Rio de Janeiro city. Local neighborhoods are constructed by means of aggregation of contiguous census tracts which are homogeneous regarding socioeconomic indicators. METHODOLOGY: Local neighborhoods were created using the SKATER method (TerraView software). Criteria used for socioeconomic homogeneity were based on four census tract indicators (income, education, persons per household, and percentage of population in the 0-4-year age bracket) considering a minimum population of 5,000 people living in each local neighborhood. The process took into account the geographic boundaries between administrative neighborhoods (a political-administrative division larger than a local neighborhood, but smaller than a borough) and natural geographic barriers. RESULTS: The original 8,145 census tracts were collapsed into 794 local neighborhoods, distributed along 158 administrative neighborhoods. Local neighborhoods contained a mean of 10 census tracts, and there were an average of five local neighborhoods per administrative neighborhood.The local neighborhood units demarcated in this study are less socioeconomically heterogeneous than the administrative neighborhoods and provide a means for decreasing the well-known statistical variability of indicators based on census tracts. The local neighborhoods were able to distinguish between different areas within administrative neighborhoods, particularly in relation to squatter settlements. CONCLUSION: Although the literature on neighborhood and health is increasing, little attention has been paid to criteria for demarcating neighborhoods. The proposed method is well-structured, available in open-access software, and easily reproducible, so we expect that new experiments will be conducted to evaluate its potential use in other settings. The method is thus a potentially important contribution to research on intra-urban differentials, particularly concerning contextual factors and their implications for different health outcomes. PMID- 20587047 TI - Sero-prevalence and risk factors for hepatitis B virus infection among health care workers in a tertiary hospital in Uganda. AB - BACKGROUND: Hepatitis B virus (HBV) infection is a global public health challenge. Prevalence of current hepatitis B virus infection in the general population in Uganda is about 10%. Health care workers (HCW) have an extra risk of getting infected from their workplace and yet they are not routinely vaccinated against HBV infection. This study aimed at estimating prevalence of hepatitis B virus infection and associated risk factors among health care workers in a tertiary hospital in Uganda. METHODS: Data were obtained from a cross sectional survey conducted in Mulago, a national referral and teaching hospital in Uganda among health care workers in 2003. A proportionate to size random sample was drawn per health care worker category. A structured questionnaire was used to collect data on socio-demographic characteristics and risk factors. ELISA was used to test sera for HBsAg, anti-HBs and total anti-HBc. Descriptive and logistic regression models were used for analysis. RESULTS: Among the 370 participants, the sero-prevalence of current hepatitis B virus infection was 8.1%; while prevalence of life time exposure to hepatitis B virus infection was 48.1%. Prevalence of needle stick injuries and exposure to mucous membranes was 67.8% and 41.0% respectively. Cuts were also common with 31.7% of doctors reporting a cut in a period of one year preceding the survey. Consistent use of gloves was reported by 55.4% of respondents. The laboratory technicians (18.0% of respondents) were the least likely to consistently use gloves. Only 6.2% of respondents were vaccinated against hepatitis B virus infection and 48.9% were susceptible and could potentially be protected through vaccination. Longer duration in service was associated with a lower risk of current infection (OR = 0.13; p value = 0.048). Being a nursing assistant (OR = 17.78; p value = 0.007) or a laboratory technician (OR = 12.23; p value = 0.009) were associated with a higher risk of current hepatitis B virus infection. Laboratory technicians (OR = 3.99; p value = 0.023) and individuals with no training in infection prevention in last five years (OR = 1.85; p value = 0.015) were more likely to have been exposed to hepatitis B virus infection before. CONCLUSIONS: The prevalence of current and life time exposure to hepatitis B virus infection was high. Exposure to potentially infectious body fluids was high and yet only a small percentage of HCW were vaccinated. There is need to vaccinate all health care workers as a matter of policy and ensure a safer work environment. PMID- 20587048 TI - Surviving meningococcal septic shock in childhood: long-term overall outcome and the effect on health-related quality of life. AB - INTRODUCTION: The purpose of this study was to evaluate associations between long term physical and psychological outcome variables in patients who survived meningococcal septic shock (MSS) in childhood. METHODS: The study population was made up of all MSS patients requiring intensive care treatment between 1988 and 2001. RESULTS: A total of 120 patients visited the follow-up clinic (age at paediatric intensive care unit (PICU) admission 3.1 years; follow-up interval 9.8 years; age at follow-up 14.5 years (all medians)). Four major outcomes were considered: 1) major physical sequelae (defined as major scars and/or orthopaedic sequelae) (29/120), 2) mild neurological impairments (39/120), 3) problem behaviour (defined as a total score above the 90th percentile of the reference groups on questionnaires to screen for psychopathology) (16/114) and 4) total intelligence quotient < 85 (18/115). No differences were found between patients with major physical sequelae and patients without major physical sequelae as to the presence of problem behaviour or total IQ < 85. Also, no differences were found between patients with mild neurological impairments and patients without as to the presence of problem behaviour or total IQ < 85. Finally, no differences were found between patients with major physical sequelae and patients without as to the presence of mild neurological sequelae. Less favourable scores on behavioural and emotional problems were significantly associated with poorer health-related quality of life (HR-QoL). HR-QoL scores were to a lesser amount predicted by severity of illness at time of PICU admission or by adverse physical outcome. CONCLUSIONS: Long-term adverse physical and psychological outcomes in survivors of MSS did not seem to be associated. Poorer HR-QoL was mainly predicted by problem behaviour. PMID- 20587049 TI - Rampant historical mitochondrial genome introgression between two species of green pond frogs, Pelophylax nigromaculatus and P. plancyi. AB - BACKGROUND: Mitochondrial introgression may result in the mitochondrial genome of one species being replaced by that of another species without leaving any trace of past hybridization in its nuclear genome. Such introgression can confuse the species genealogy estimates and lead to absurd inferences of species history. We used a phylogenetic approach to explore the potential mitochondrial genome introgression event(s) between two closely related green pond frog species, Pelophylax nigromaculatus and P. plancyi. RESULTS: DNA sequence data of one mitochondrial and two nuclear genes from an extensive sampling of the two species were collected, and the genealogies of the three genes were constructed and compared. While the two nuclear genes congruently showed mutual reciprocal monophyly of both species, the mitochondrial phylogeny separated a Korean P. nigromaculatus clade, a paraphyletic central China P. plancyi assemblage, and a large well-supported introgression clade. Within the introgression clade, the mitochondrial haplotypes of the two species were mixed together. This reticulated pattern can be most parsimoniously explained by an ancient mitochondrial introgression event from P. plancyi to P. nigromaculatus that occurred at least 1.36 MYA, followed by multiple recent introgression events from P. nigromaculatus back to P. plancyi within the last 0.63 MY. The re-constitution of previously co adapted genomes in P. plancyi may be responsible for the recent rampant introgression events. The Korean P. nigromaculatus clade likely represents the only surviving "true" mitochondrial lineage of P. nigromaculatus, and the central China P. plancyi assemblage likely represents the "original" P. plancyi mitochondrial lineage. Refugia in the Korean Peninsula and central China may have played a significant role in preserving these ancient lineages. CONCLUSIONS: The majority of individuals in the two species have either introgressed (P. nigromaculatus) or reclaimed (P. plancyi) mitochondrial genomes while no trace of past hybridization in their nuclear genomes was detected. Asymmetrical reproductive ability of hybrids and continuous backcrossing are likely responsible for the observed mitochondrial introgression. This case is unique in that it includes an ancient "forward" introgression and many recent "backward" introgressions, which re-constitutes the original nuclear and mitochondrial genomes of P. plancyi. This hybrid system provides an excellent opportunity to study cyto-nuclear interaction and co-adaptation. PMID- 20587050 TI - Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH. AB - BACKGROUND: Microarray-based comparative genomic hybridization (aCGH) is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo) arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC) arrays, yet this has not been systematically studied in a clinical diagnostic setting. RESULTS: To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6%) had a copy number imbalance of potential clinical significance detectable by the whole genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater. CONCLUSIONS: Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing. PMID- 20587051 TI - What can global health institutions do to help strengthen health systems in low income countries? AB - Weaknesses in health systems contribute to a failure to improve health outcomes in developing countries, despite increased official development assistance. Changes in the demands on health systems, as well as their scope to respond, mean that the situation is likely to become more problematic in the future. Diverse global initiatives seek to strengthen health systems, but progress will require better coordination between them, use of strategies based on the best available evidence obtained especially from evaluation of large scale programs, and improved global aid architecture that supports these processes. This paper sets out the case for global leadership to support health systems investments and help ensure the synergies between vertical and horizontal programs that are essential for effective functioning of health systems. At national level, it is essential to increase capacity to manage and deliver services, situate interventions firmly within national strategies, ensure effective implementation, and co-ordinate external support with local resources. Health systems performance should be monitored, with clear lines of accountability, and reforms should build on evidence of what works in what circumstances. PMID- 20587052 TI - Fructose-1, 6-diphosphate (FDP) as a novel antidote for yellow oleander-induced cardiac toxicity: a randomized controlled double blind study. AB - BACKGROUND: Cardiac toxicity due to ingestion of oleander plant seeds in Sri Lanka and some other South Asian countries is very common. At present symptomatic oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to gastric decontamination and atropine administration. The only proven effective antidote is digoxin antibodies but these are not available for routine use because of the high cost. The main objective of this study is to investigate the effectiveness of a new and inexpensive antidote for patients with life threatening arrhythmias due oleander poisoning. METHOD/DESIGN: We set up a randomised double blind clinical trial to assess the effectiveness of Fructose 1, 6 diphosphate (FDP) in acute yellow oleander poisoning patients admitted to the adult medical wards of a tertiary hospital in Sri Lanka. Patients will be initially resuscitated following the national guidelines and eligible patients will be randomised to receive either FDP or an equal amount of normal saline. The primary outcome measure for this study is the sustained reversion to sinus rhythm with a heart rate greater than 50/min within 2 hours of completion of FDP/placebo bolus. Secondary outcomes include death, reversal of hyperkalaemia on the 6, 12, 18 and 24 hour samples and maintenance of sinus rhythm on the holter monitor. Analysis will be on intention to-treat. DISCUSSION: This trial will provide information on the effectiveness of FDP in yellow oleander poisoning. If FDP is effective in cardiac glycoside toxicity, it would provide substantial benefit to the patients in rural Asia. The drug is inexpensive and thus could be made available at primary care hospitals if proven to be effective. TRIAL REGISTRATION: Current Controlled trial ISRCTN71018309. PMID- 20587053 TI - Occurrence and sequence of Sphaeroides Heme Protein and diheme cytochrome C in purple photosynthetic bacteria in the family Rhodobacteraceae. AB - BACKGROUND: Sphaeroides Heme Protein (SHP) was discovered in the purple photosynthetic bacterium, Rhodobacter sphaeroides, and is the only known c-type heme protein that binds oxygen. Although initially not believed to be widespread among the photosynthetic bacteria, the gene has now been found in more than 40 species of proteobacteria and generally appears to be regulated. Rb. sphaeroides is exceptional in not having regulatory genes associated with the operon. We have thus analyzed additional purple bacteria for the SHP gene and examined the genetic context to obtain new insights into the operon, its distribution, and possible function. RESULTS: We found SHP in 9 out of 10 strains of Rb. sphaeroides and in 5 out of 10 purple photosynthetic bacterial species in the family Rhodobacteraceae. We found a remarkable similarity within the family including the lack of regulatory genes. Within the proteobacteria as a whole, SHP is part of a 3-6 gene operon that includes a membrane-spanning diheme cytochrome b and one or two diheme cytochromes c. Other genes in the operon include one of three distinct sensor kinase - response regulators, depending on species, that are likely to regulate SHP. CONCLUSIONS: SHP is not as rare as generally believed and has a role to play in the photosynthetic bacteria. Furthermore, the two companion cytochromes along with SHP are likely to function as an electron transfer pathway that results in the reduction of SHP by quinol and formation of the oxygen complex, which may function as an oxygenase. The three distinct sensors suggest at least as many separate functional roles for SHP. Two of the sensors are not well characterized, but the third is homologous to the QseC quorum sensor, which is present in a number of pathogens and typically appears to regulate genes involved in virulence. PMID- 20587054 TI - Aquaporins in the wild: natural genetic diversity and selective pressure in the PIP gene family in five Neotropical tree species. AB - BACKGROUND: Tropical trees undergo severe stress through seasonal drought and flooding, and the ability of these species to respond may be a major factor in their survival in tropical ecosystems, particularly in relation to global climate change. Aquaporins are involved in the regulation of water flow and have been shown to be involved in drought response; they may therefore play a major adaptive role in these species. We describe genetic diversity in the PIP sub family of the widespread gene family of Aquaporins in five Neotropical tree species covering four botanical families. RESULTS: PIP Aquaporin subfamily genes were isolated, and their DNA sequence polymorphisms characterised in natural populations. Sequence data were analysed with statistical tests of standard neutral equilibrium and demographic scenarios simulated to compare with the observed results. Chloroplast SSRs were also used to test demographic transitions. Most gene fragments are highly polymorphic and display signatures of balancing selection or bottlenecks; chloroplast SSR markers have significant statistics that do not conform to expectations for population bottlenecks. Although not incompatible with a purely demographic scenario, the combination of all tests tends to favour a selective interpretation of extant gene diversity. CONCLUSIONS: Tropical tree PIP genes may generally undergo balancing selection, which may maintain high levels of genetic diversity at these loci. Genetic variation at PIP genes may represent a response to variable environmental conditions. PMID- 20587055 TI - Multidrug resistant Kluyvera ascorbata septicemia in an adult patient: a case report. AB - INTRODUCTION: Kluyvera ascorbata has become increasingly significant due to its potential to cause a wide range of infections, as well as its ability to transfer gene encoding for CTX-M- type extended spectrum B-lactamases (ESBLs) to other Enterobacteriaceae. CASE PRESENTATION: We report the case of a 64-year-old African-American male diagnosed with severe sepsis due to a multidrug resistant Kluyvera ascorbata, which was isolated from his blood. He was treated with meropenem and had a favorable outcome. CONCLUSION: To the best of our knowledge, this is the first case report of a multidrug resistant Kluyvera ascorbata isolated from the blood in an adult patient with sepsis. PMID- 20587056 TI - Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy. AB - BACKGROUND: The pro-nociceptive kinin B1 receptor (B1R) is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ) diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. METHODS: Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p.), and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p.) were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR) of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I)-HPP-desArg10-Hoe 140) were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK) and antagonists (SSR240612 and R-715) were measured on neuropathic pain manifestations. RESULTS: STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1beta, TNF-alpha, TRPV1) and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. CONCLUSION: The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats. PMID- 20587057 TI - Development of an online information and support resource for adolescent idiopathic scoliosis patients considering surgery: perspectives of health care providers. AB - BACKGROUND: Adolescents with idiopathic scoliosis who are considering spinal surgery face a major decision that requires access to in-depth information and support. Unfortunately, most online resources provide incomplete and inconsistent information and minimal social support. The aim of this study was to develop an online information and support resource for adolescent idiopathic scoliosis (AIS) patients considering spinal surgery. Prior to website development, a user-based needs assessment was conducted. The needs assessment involved a total of six focus groups with three stakeholder groups: (1) post-operative AIS patients or surgical candidates (10-18 years) (n = 11), (2) their parents (n = 6) and (3) health care providers (n = 11). This paper reports on the findings from focus groups with health care providers. METHODS: Focus group methodology was used to invite a range of perspectives and stimulate discussion. During audio-recorded focus groups, an emergent table of website content was presented to participants for assessment of relevance, viability and comprehensiveness in targeting global domains of need. Specifically, effective presentation of content, desired aspects of information and support, and discussions about the value of peer support and the role of health professionals were addressed. Focus group transcripts were then subject to content analysis through a constant comparative review and analysis. RESULTS: Two focus groups were held with health care providers, consisting of 5 and 6 members respectively. Clinicians provided their perceptions of the information and support needs of surgical patients and their families and how this information and support should be delivered using internet technology. Health care providers proposed four key suggestions to consider in the development of this online resource: (1) create the website with the target audience in mind; (2) clearly state the purpose of the website and organize website content to support the user; (3) offer a professionally-moderated interactive support component; and (4) ensure accessibility of website information and support by considering the age, gender, reading level and geographic location of potential users. CONCLUSIONS: Health care providers collectively identified the need for the development of an online information and support resource for adolescents considering surgery for AIS and their families and described the proposed website as a positive and needed adjunct to current clinical care. PMID- 20587058 TI - Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes. AB - BACKGROUND: Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. Momordica charantia or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes. METHODS: Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR). RESULTS: Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor gamma (PPARgamma) and sterol regulatory element binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol. CONCLUSION: Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans. PMID- 20587059 TI - Mitochondrial DNA, chloroplast DNA and the origins of development in eukaryotic organisms. AB - BACKGROUND: Several proposals have been made to explain the rise of multicellular life forms. An internal environment can be created and controlled, germ cells can be protected in novel structures, and increased organismal size allows a "division of labor" among cell types. These proposals describe advantages of multicellular versus unicellular organisms at levels of organization at or above the individual cell. I focus on a subsequent phase of evolution, when multicellular organisms initiated the process of development that later became the more complex embryonic development found in animals and plants. The advantage here is realized at the level of the mitochondrion and chloroplast. HYPOTHESIS: The extreme instability of DNA in mitochondria and chloroplasts has not been widely appreciated even though it was first reported four decades ago. Here, I show that the evolutionary success of multicellular animals and plants can be traced to the protection of organellar DNA. Three stages are envisioned. Sequestration allowed mitochondria and chloroplasts to be placed in "quiet" germ line cells so that their DNA is not exposed to the oxidative stress produced by these organelles in "active" somatic cells. This advantage then provided Opportunity, a period of time during which novel processes arose for signaling within and between cells and (in animals) for cell-cell recognition molecules to evolve. Development then led to the enormous diversity of animals and plants. IMPLICATIONS: The potency of a somatic stem cell is its potential to generate cell types other than itself, and this is a systems property. One of the biochemical properties required for stemness to emerge from a population of cells might be the metabolic quiescence that protects organellar DNA from oxidative stress. PMID- 20587060 TI - Susceptible cell lines for the production of porcine reproductive and respiratory syndrome virus by stable transfection of sialoadhesin and CD163. AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes major economic losses in the pig industry worldwide. In vivo, the virus infects a subpopulation of tissue macrophages. In vitro, PRRSV only replicates in primary pig macrophages and African green monkey kidney derived cells, such as Marc-145. The latter is currently used for vaccine production. However, since virus entry in Marc-145 cells is different compared to entry in primary macrophages, specific epitopes associated with virus entry could potentially alter upon growth on Marc 145 cells. To avoid this, we constructed CHO and PK15 cell lines recombinantly expressing the PRRSV receptors involved in virus entry into macrophages, sialoadhesin (Sn) and CD163 (CHOSn-CD163 and PK15Sn-CD163) and evaluated their potential for production of PRRSV. RESULTS: Detailed analysis of PRRSV infection revealed that LV and VR-2332 virus particles could attach to and internalize into the CHOSn-CD163 and PK15Sn-CD163 cells. Initially, this occurred less efficiently for macrophage grown virus than for Marc-145 grown virus. Upon internalization, disassembly of the virus particles was observed. The two cell lines could be infected with PRRSV strains LV and VR-2332. However, it was observed that Marc 145 grown virus infected the cells more efficiently than macrophage grown virus. If the cells were treated with neuraminidase to remove cis-acting sialic acids that hinder the interaction of the virus with Sn, the amount of infected cells with macrophage grown virus increased. Comparison of both cell lines showed that the PK15Sn-CD163 cell line gave in general better results than the CHOSn-CD163 cell line. Only 2 out of 5 PRRSV strains replicated well in CHOSn-CD163 cells. Furthermore, the virus titer of all 5 PRRSV strains produced after passaging in PK15Sn-CD163 cells was similar to the virus titer of those strains produced in Marc-145 cells. Analysis of the sequence of the structural proteins of original virus and virus grown for 5 passages on PK15Sn-CD163 cells showed either no amino acid (aa) changes (VR-2332 and 07V063), one aa (LV), two aa (08V194) or three aa (08V204) changes. None of these changes are situated in known neutralizing epitopes. CONCLUSIONS: A PRRSV susceptible cell line was constructed that can grow virus to similar levels compared to currently available cell lines. Mutations induced by growth on this cell lines were either absent or minimal and located outside known neutralizing epitopes. Together, the results show that this cell line can be used to produce vaccine virus and for PRRSV virus isolation. PMID- 20587061 TI - Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). AB - BACKGROUND: HPV is important in a subset of HNSCC. Our meta-analysis determined the clinical characteristics of HPV-related HNSCC. METHOD: Pubmed search terms "HPV" and "HNSCC" were used to identify 34 studies since 1980. We obtained pooled adjusted odds ratio (OR) or hazard ratio (HR) using random or fixed-effects model and compared OS depicted in forest plot. RESULTS: A total of 5681 patients were included. The prevalence of HPV+ tumors was 22%, with 86.7% of HPV16+ genotype. The OR for HNSCC in HPV16+ patients was 4.44 (95% CI = 2.87-6.02). HPV status was associated with p16 expression (adj OR = 3.00; 0.90-9.70), and HPV+ tumors were less likely to harbor p53 mutations (adj OR = 0.21; 0.04-0.38). The HR for death in HPV+ patients was 0.42 (0.27-0.57). HPV+ HNSCC also had a better response to therapy. CONCLUSION: HPV+ HNSCC are established as a separate biologic entity. Prospective trials are needed to establish the optimal therapy for HPV+ HNSCC. PMID- 20587062 TI - A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members. AB - BACKGROUND: The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. METHODS: The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. RESULTS: Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. CONCLUSIONS: Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further. PMID- 20587063 TI - The role of noise and positive feedback in the onset of autosomal dominant diseases. AB - BACKGROUND: Autosomal dominant (AD) diseases result when a single mutant or non functioning gene is present on an autosomal chromosome. These diseases often do not emerge at birth. There are presently two prevailing theories explaining the expression of AD diseases. One explanation originates from the Knudson two-hit theory of hereditary cancers, where loss of heterozygosity or occurrence of somatic mutations impairs the function of the wild-type copy. While these somatic second hits may be sufficient for stable disease states, it is often difficult to determine if their occurrence necessarily marks the initiation of disease progression. A more direct consequence of a heterozygous genetic background is haploinsufficiency, referring to a lack of sufficient gene function due to reduced wild-type gene copy number; however, haploinsufficiency can involve a variety of additional mechanisms, such as noise in gene expression or protein levels, injury and second hit mutations in other genes. In this study, we explore the possible contribution to the onset of autosomal dominant diseases from intrinsic factors, such as those determined by the structure of the molecular networks governing normal cellular physiology. RESULTS: First, simple models of single gene insufficiency using the positive feedback loops that may be derived from a three-component network were studied by computer simulation using Bionet software. The network structure is shown to affect the dynamics considerably; some networks are relatively stable even when large stochastic variations in are present, while others exhibit switch-like dynamics. In the latter cases, once the network switches over to the disease state it remains in that state permanently. Model pathways for two autosomal dominant diseases, AD polycystic kidney disease and mature onset diabetes of youth (MODY) were simulated and the results are compared to known disease characteristics. CONCLUSIONS: By identifying the intrinsic mechanisms involved in the onset of AD diseases, it may be possible to better assess risk factors as well as lead to potential new drug targets. To illustrate the applicability of this study of pathway dynamics, we simulated the primary pathways involved in two autosomal dominant diseases, Polycystic Kidney Disease (PKD) and mature onset diabetes of youth (MODY). Simulations demonstrate that some of the primary disease characteristics are consistent with the positive feedback-stochastic variation theory presented here. This has implications for new drug targets to control these diseases by blocking the positive feedback loop in the relevant pathways. PMID- 20587064 TI - Treatment of reducible unstable fractures of the distal radius in adults: a randomised controlled trial of De Palma percutaneous pinning versus bridging external fixation. AB - BACKGROUND: At present, there is no conclusive evidence regarding the best treatment method for reducible unstable fractures of the distal radius. This study compared the effectiveness of two methods used in surgical treatment of such fractures: percutaneous pinning and external fixation. METHODS: We randomly allocated 100 patients into two groups treated surgically with modified De Palma percutaneous pinning and bridging external fixation. Independent but not blinded evaluators administered the DASH quality-of-life questionnaire at postoperative months 6 and 24, performed functional assessment of pain, range of motion, and palm grip strength, and radiographic examinations (volar and radial angle, and height of the radius) before the operation, immediately afterwards, and at 6 and 24 months postoperative. Modified De Palma percutaneous pinning patients used an above-elbow cast whereas external fixation group had unrestricted elbow motion after surgery. Patients who for any reason demonstrated treatment failure or required additional interventions were followed up and their results were included in the group into which these patients had initially been randomised according to the intention-to-treat principle. A significance level of 5% (alpha = 0.05). was used for all statistical tests, such that tests presenting a p-value less than 0.05 were considered statistically significant. RESULTS: Ninety one (58.8 mean age and 66 participants were female) were included in the final assessment at 24 months. The DASH questionnaire evaluation showed a statistically significant result favouring the De Palma group (mean difference = -7.1 p = 0.044) after six months, but this was not maintained at 24 months. There were no statistically differences between the groups with respect to palm grip strength. Analysis of the range-of-motion limitation index (uninjured side minus affected side motion of) showed a statistical difference (mean difference = 2.4 p = 0.043) favoring the external fixator group with regard to the supination movement 6 months after the operation; however, this was not maintained at 24 months. The final results of the radiographic evaluation were similar for the two groups. Overall, five patients developed complications: two with De Palma pinning and three with external fixation. CONCLUSION: There was a small statistically significant difference favouring the De Palma method in early functional at 6 months according to the DASH questionnaire, and for supination movement favouring the fixator group. However, both were not clinical relevant. By 24 months the groups were similar for all outcomes TRIAL REGISTRATION: Current Controlled Trials ISRCTN04892785. PMID- 20587065 TI - Spatial normalization improves the quality of genotype calling for Affymetrix SNP 6.0 arrays. AB - BACKGROUND: Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms. RESULTS: Application of the spatial bias adjustments on HapMap samples resulted in higher genotype call rates with equal or even better accuracy for thousands of SNPs. Consequently the normalization procedure is expected to lead to more meaningful biological inferences and could be valuable for genome-wide SNP analysis. CONCLUSIONS: Spatial normalization can potentially rescue thousands of SNPs in a genetic study at the small cost of computational time. The approach is implemented in R and available from the authors upon request. PMID- 20587066 TI - Insecticidal activity of two proteases against Spodoptera frugiperda larvae infected with recombinant baculoviruses. AB - BACKGROUND: Baculovirus comprise the largest group of insect viruses most studied worldwide, mainly because they efficiently kill agricultural insect pests. In this study, two recombinant baculoviruses containing the ScathL gene from Sarcophaga peregrina (vSynScathL), and the Keratinase gene from the fungus Aspergillus fumigatus (vSynKerat), were constructed, and their insecticidal properties analysed against Spodoptera frugiperda larvae. RESULTS: Bioassays of third-instar and neonate S. frugiperda larvae with vSynScathL and vSynKerat showed a decrease in the time needed to kill the infected insects when compared to the wild type virus. We have also shown that both recombinants were able to increase phenoloxidase activity in the hemolymph of S. frugiperda larvae. The expression of proteases in infected larvae resulted in destruction of internal tissues late in infection, which could be the reason for the increased viral speed of kill. CONCLUSIONS: Baculoviruses and their recombinant forms constitute viable alternatives to chemical insecticides. Recombinant baculoviruses containing protease genes can be added to the list of engineered baculoviruses with great potential to be used in integrated pest management programs. PMID- 20587067 TI - Pituitary hCG production and cerebral tuberculosis mimicking disease progression during chemotherapy for an advanced ovarian germ cell tumour. AB - BACKGROUND: Ovarian germ cell tumours (OGCT) are rare but are usually curable with chemotherapy, even when presenting with advanced disease. The majority of OGCT produce the tumour markers, hCG and/or AFP which can be helpful in the diagnosis and monitoring the response to treatment. CASE PRESENTATION: In this case of a 36 year old woman, the elevated hCG level at presentation was helpful in making a clinical diagnosis of OGCT in a patient too unwell to permit a tissue diagnosis. Cisplatin based combination chemotherapy produced an initial normalisation of the hCG level, but later in treatment the patient developed new cerebral lesions and a rising serum hCG suggestive of disease progression. Further investigations suggested that the CNS lesions were cerebral TB and that the low levels of hCG elevations was likely to be pituitary in origin. Chemotherapy treatment was continued along with anti-tuberculous therapy and 24 months after successful completion of therapy the patient remains disease free. CONCLUSIONS: In the treatment of cancer patients it may be helpful to consider the potential non-malignant causes of new CNS lesions and that low hCG elevations may result from physiology rather than pathology in selected cases. PMID- 20587068 TI - Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells. AB - BACKGROUND: The constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumours. In particular, MMP-2 and MMP-9 have been reported to be closely associated with invasion and angiogenesis in malignant gliomas. Our study aimed to evaluate the antitumour effects of MMI-166 (Nalpha-[4-(2-Phenyl-2H- tetrazole-5-yl) phenyl sulfonyl]-D-tryptophan), a third generation MMP inhibitor, on three human glioma cell lines (T98G, U87MG, and ONS12) in vitro and in vivo. METHODS: The effects of MMI-166 on the gelatinolytic activity was analysed by gelatine zymography. The anti-invasive effect of MMI-166 was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by MMI-166 was determined by the MTT assay. The effect of MMI-166 on an orthotropic implantation model using athymic mice was also evaluated. RESULTS: Gelatine zymography revealed that MMP-2 and MMP-9 activities were suppressed by MMI-166. The invasion of glioma cells was suppressed by MMI-166. The angiogenesis assay showed that MMI 166 had a suppressive effect on glioma cell-induced angiogenesis. However, MMI 166 did not suppress glioma cell proliferation in the MTT assay. In vivo, MMI-166 suppressed tumour growth in athymic mice implanted orthotropically with T98G cells and showed an inhibitory effect on tumour-induced angiogenesis and tumour growth. This is the first report of the effect of a third generation MMP inhibitor on malignant glioma cells. CONCLUSIONS: These results suggest that MMI 166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas. PMID- 20587069 TI - A high-density Diversity Arrays Technology (DArT) microarray for genome-wide genotyping in Eucalyptus. AB - BACKGROUND: A number of molecular marker technologies have allowed important advances in the understanding of the genetics and evolution of Eucalyptus, a genus that includes over 700 species, some of which are used worldwide in plantation forestry. Nevertheless, the average marker density achieved with current technologies remains at the level of a few hundred markers per population. Furthermore, the transferability of markers produced with most existing technology across species and pedigrees is usually very limited. High throughput, combined with wide genome coverage and high transferability are necessary to increase the resolution, speed and utility of molecular marker technology in eucalypts. We report the development of a high-density DArT genome profiling resource and demonstrate its potential for genome-wide diversity analysis and linkage mapping in several species of Eucalyptus. FINDINGS: After testing several genome complexity reduction methods we identified the PstI/TaqI method as the most effective for Eucalyptus and developed 18 genomic libraries from PstI/TaqI representations of 64 different Eucalyptus species. A total of 23,808 cloned DNA fragments were screened and 13,300 (56%) were found to be polymorphic among 284 individuals. After a redundancy analysis, 6,528 markers were selected for the operational array and these were supplemented with 1,152 additional clones taken from a library made from the E. grandis tree whose genome has been sequenced. Performance validation for diversity studies revealed 4,752 polymorphic markers among 174 individuals. Additionally, 5,013 markers showed segregation when screened using six inter-specific mapping pedigrees, with an average of 2,211 polymorphic markers per pedigree and a minimum of 859 polymorphic markers that were shared between any two pedigrees. CONCLUSIONS: This operational DArT array will deliver 1,000-2,000 polymorphic markers for linkage mapping in most eucalypt pedigrees and thus provide high genome coverage. This array will also provide a high-throughput platform for population genetics and phylogenetics in Eucalyptus. The transferability of DArT across species and pedigrees is particularly valuable for a large genus such as Eucalyptus and will facilitate the transfer of information between different studies. Furthermore, the DArT marker array will provide a high-resolution link between phenotypes in populations and the Eucalyptus reference genome, which will soon be completed. PMID- 20587070 TI - Expression of bone morphogenetic protein-2 and its receptors in epithelial ovarian cancer and their influence on the prognosis of ovarian cancer patients. AB - BACKGROUND: To determine the expression of bone morphogenetic protein-2 (BMP-2) and its receptors BMPRIA, BMPRIB, and BMPRII in epithelial ovarian cancer (EOC) and to analyze their influence on the prognosis of ovarian cancer patients. METHODS: Semi-quantitative RT-PCR and western blot were applied to detect the expression of BMP-2 and its receptors BMPRIA, BMPRIB, and BMPRII in EOC, benign ovarian tumors, and normal ovarian tissue at the mRNA and protein levels. Immunohistochemistry was used to determine the expression of BMP-2 and its receptors in 100 patients with EOC to analyze their influence on the five-year survival rate and survival time of ovarian cancer patients. RESULTS: (1) The mRNA and protein expression levels of BMP-2, BMPRIB, and BMPRII in ovarian cancer tissue were remarkably lower than those in benign ovarian tumors and normal ovarian tissue, while no significant differences in BMPRIA expression level was found among the three kinds of tissues. (2) The five-year survival rate and the average survival time after surgery of EOC patients with positive expression of BMP-2, BMPRIB, and BMPRII were remarkably higher than those of patients with negative expression of BMP-2, BMPRIB, and BMPRII. BMPRIA expression was not associated with the five-year survival rate or with the average survival time of ovarian cancer patients. CONCLUSIONS: BMP-2, BMPRIB, and BMPRII exhibited low expression in EOC tissue, and variation or loss of expression may indicate poor prognosis for ovarian cancer patients. PMID- 20587071 TI - Spinal pain and nutrition in adolescents--an exploratory cross-sectional study. AB - BACKGROUND: Spinal pain is an important health issue for adolescents resulting in functional limitations for many and increasing the risk of spinal pain in adulthood. Whilst human and animal studies suggest nutrition could influence spinal pain, this has not been investigated in adolescents. The objective of this exploratory cross sectional study was to evaluate associations between diet and adolescent spinal pain. METHODS: This study surveyed the spinal pain (neck and back) and nutrition (specific nutrients, broad food groups, diet quality and dietary pattern) of 1424 male and female adolescents at 14 years of age, in Western Australia. RESULTS: Back or neck pain were experienced by around half of the adolescents, with females more likely to experience spinal pain. Nutrition differed between sexes and deviated from optimal intakes. Vitamin B12, eggs, cereals and meat consumption were related to spinal pain in sex specific multivariate analyses including primary carer education level and adolescent waist girth and smoking. CONCLUSIONS: The findings of this study suggest that certain aspects of diet may have an association with spinal pain in adolescence. PMID- 20587072 TI - Malignant mammary tumor in female dogs: environmental contaminants. AB - Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID- 20587073 TI - A process optimization for bio-catalytic production of substituted catechols (3 nitrocatechol and 3-methylcatechol. AB - BACKGROUND: Substituted catechols are important precursors for large-scale synthesis of pharmaceuticals and other industrial products. Most of the reported chemical synthesis methods are expensive and insufficient at industrial level. However, biological processes for production of substituted catechols could be highly selective and suitable for industrial purposes. RESULTS: We have optimized a process for bio-catalytic production of 3-substituted catechols viz. 3 nitrocatechol (3-NC) and 3-methylcatechol (3-MC) at pilot scale. Amongst the screened strains, two strains viz. Pseudomonas putida strain (F1) and recombinant Escherichia coli expression clone (pDTG602) harboring first two genes of toluene degradation pathway were found to accumulate 3-NC and 3-MC respectively. Various parameters such as amount of nutrients, pH, temperature, substrate concentration, aeration, inoculums size, culture volume, toxicity of substrate and product, down stream extraction, single step and two-step biotransformation were optimized at laboratory scale to obtain high yields of 3-substituted catechols. Subsequently, pilot scale studies were performed in 2.5 liter bioreactor. The rate of product accumulation at pilot scale significantly increased up to approximately 90-95% with time and high yields of 3-NC (10 mM) and 3-MC (12 mM) were obtained. CONCLUSION: The biocatalytic production of 3-substituted catechols viz. 3-NC and 3-MC depend on some crucial parameters to obtain maximum yields of the product at pilot scale. The process optimized for production of 3-substituted catechols by using the organisms P. putida (F1) and recombinant E. coli expression clone (pDTG602) may be useful for industrial application. PMID- 20587074 TI - Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain. AB - BACKGROUND: Several receptor tyrosine kinases (RTKs) such as EGFR, FGFR, TRK, and VEGFR are capable of localizing in the cell nucleus in addition to their usual plasma membrane localization. Recent reports also demonstrate that nuclear localized RTKs have important cellular functions such as transcriptional activation. On the basis of preliminary bioinformatic analysis, additional RTKs, including receptor tyrosine kinase-like orphan receptor 1 (Ror1) were predicted to have the potential for nuclear subcellular localization. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system. Because the nuclear localization capability of the Ror1 cytoplasmic domain has not been reported, we examined the cellular expression distribution of this region. RESULTS: The Ror1 cytoplasmic region was amplified and cloned into reporter constructs with fluorescent tags. Following transfection, the nuclear distribution patterns of transiently expressed fusion proteins were observed. Serial deletion constructs were then used to map the juxtamembrane domain of Ror1 (aa_471-513) for this nuclear translocation activity. Further site-directed mutagenesis suggested that a KxxK-16 aa-KxxK sequence at residues 486-509 is responsible for the nuclear translocation interaction. Subsequent immunofluorescence analysis by cotransfection of Ran and Ror1 implied that the nuclear translocation event of Ror1 might be mediated through the Ran pathway. CONCLUSIONS: We have predicted several RTKs that contain the nuclear localization signals. This is the first report to suggest that the juxtamembrane domain of the Ror1 cytoplasmic region mediates the translocation event. Ran GTPase is also implicated in this event. Our study might be beneficial in future research to understand the Ror1 biological signaling pathway. PMID- 20587075 TI - Genetic evidence of multiple loci in dystocia--difficult labour. AB - BACKGROUND: Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. METHODS: A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3. RESULTS: We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. CONCLUSIONS: Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts. PMID- 20587077 TI - A plethora of angiopoietin-2 effects during clinical sepsis. AB - The interesting study by Davis and colleagues in the current issue of Critical Care expands on the increasingly recognized role of angiopoietins in human sepsis but raises a number of questions, which are discussed in this commentary. The authors describe an association between elevated angiopoietin (ang)-2 levels and impaired vascular reactivity, measured by the partly nitric oxide-dependent finger hyperemic response to forearm vascular occlusion, in patients with sepsis. This suggests that the ang-1/2-Tie2 system is involved in a number of pathophysiologic, phenotypic and perhaps prognostic alterations in human sepsis, on top of the effect on pulmonary endothelial barrier function. The novel inflammatory route may be a target for future therapeutic studies in human sepsis and acute lung injury, including those with activated protein C. PMID- 20587076 TI - Clinical and preclinical translation of cell-based therapies using adipose tissue derived cells. AB - Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated. PMID- 20587079 TI - So what have data standards ever done for us? The view from metabolomics. AB - The standardization of reporting of data promises to revolutionize biology by allowing community access to data generated in laboratories across the globe. This approach has already influenced genomics and transcriptomics. Projects that have previously been viewed as being too big to implement can now be distributed across multiple sites. There are now public databases for gene sequences, transcriptomic profiling and proteomic experiments. However, progress in the metabolomic community has seemed to falter recently, and whereas there are ontologies to describe the metadata for metabolomics there are still no central repositories for the datasets themselves. Here, we examine some of the challenges and potential benefits of further efforts towards data standardization in metabolomics and metabonomics. PMID- 20587078 TI - Genomic insights into early-onset obesity. AB - The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future. PMID- 20587080 TI - Genomics through the lens of next-generation sequencing. AB - A report on the 23rd annual meeting on 'The Biology of Genomes', 11-15 May 2010, Cold Spring Harbor, USA. PMID- 20587081 TI - Mild traumatic brain injury: a risk factor for neurodegeneration. AB - Recently, it has become clear that head trauma can lead to a progressive neurodegeneration known as chronic traumatic encephalopathy. Although the medical literature also implicates head trauma as a risk factor for Alzheimer's disease, these findings are predominantly based on clinical diagnostic criteria that lack specificity. The dementia that follows head injuries or repetitive mild trauma may be caused by chronic traumatic encephalopathy, alone or in conjunction with other neurodegenerations (for example, Alzheimer's disease). Prospective longitudinal studies of head-injured individuals, with neuropathological verification, will not only improve understanding of head trauma as a risk factor for dementia but will also enhance treatment and prevention of a variety of neurodegenerative diseases. PMID- 20587082 TI - ABO blood group and other genetic variants associated with pancreatic cancer. AB - Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States. Recent reports, including genome-wide association studies and self reported blood serotype studies, have shown that individuals of European ancestry who carry non-O blood group are at an increased risk of developing pancreatic cancer. Two recent genome-wide association studies of pancreatic cancer have identified associations between pancreatic cancer risk and genetic variants in the ABO blood group gene, the locus containing the telomerase reverse transcriptase (hTERT) gene, the nuclear receptor family gene NR5A2 and a non genic region on chromosome 13q22.1. PMID- 20587083 TI - Dirty mouth? Should you clean it out? Decontamination for the prevention of pneumonia and mortality in the ICU. PMID- 20587084 TI - The complex interplay between delirium, sepsis and sedation. AB - Critically ill patients requiring mechanical ventilation frequently suffer from intensive care unit delirium, a syndrome associated with numerous poor measured outcomes. The relationship between delirium, sepsis, and sedation is complex. A discussion of the recent study ('Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS [maximizing efficacy of targeted sedation and reducing neurological dysfunction] randomized controlled trial') by Pandharipande and colleagues is presented in this commentary. PMID- 20587085 TI - The enigma that is the nucleus pulposus cell: the search goes on. AB - The development of an effective treatment for degenerative disc disease has been hampered for many years by what seems a fundamental problem; what exactly defines a nucleus pulposus (NP) cell? The paper by Gilson and colleagues elegantly re opens the debate concerning the lineage and identity of NP cells that are alike yet different from chondrocytes. As we pursue novel investigations and treatment strategies for degenerative disc disease, how do we isolate these unique cells and what is the role of the primordial notochordal cell that may well linger within the NP far longer and perhaps in a different phenotypic appearance than previously thought? The paper by Gilson and colleagues that is the subject of the present editorial presents compelling data concerning the heterogeneity of the cells of the NP, and their origin, development, maturation and function. PMID- 20587086 TI - Clinical review: Considerations for the triage of maternity care during an influenza pandemic--one institution's approach. AB - The ongoing pandemic of 2009 H1N1 swine-origin influenza A has heightened the world's attention to the reality of influenza pandemics and their unpredictable nature. Currently, the 2009 H1N1 influenza strain appears to cause mild clinical disease for the majority of those infected. However, the risk of severe disease from this strain or other future strains remains an ongoing concern and is noted in specific patient populations. Pregnant women represent a unique patient population that historically has been disproportionately affected by both seasonal and pandemic influenza outbreaks. Data thus far suggest that the current 2009 H1N1 outbreak is following this same epidemiologic tendency among pregnant women. The increased predilection to worse clinical outcomes among pregnant women has potential to produce an acute demand for critical care resources that may overwhelm supply in facilities providing maternity care. The ability of healthcare systems to optimize maternal-child health outcomes during an influenza pandemic or other biologic disaster may therefore depend on the equitable allocation of these limited resources. Triage algorithms for resource allocation have been delineated in the general medical population. However, no current guidance considers the unique aspects of pregnant women and their unborn fetuses. An approach is suggested that may help guide facilities faced with these challenges. PMID- 20587087 TI - Think (Gram) negative! AB - The increasing prevalence of multiresistant Gram-negative bacteria of the Enterobacteriaceae family in Europe is a worrisome phenomenon. Extended spectrum betalactamase-producing Escherichia coli strains are widespread in the community and are frequently imported into the hospital. Of even more concern is the spread of carbapenem-resistant strains of Klebsiella spp. from regions where they are already endemic. Antibiotic use is a main driver of antibiotic resistance, which again increases broad spectrum antibiotic use, resulting in a vicious circle that is difficult to interrupt. The present commentary highlights important findings of a surveillance study of antimicrobial use and resistance in German ICUs over 8 years with a focus on Gram-negative resistance. PMID- 20587094 TI - Evaluation of aerosol generator devices at 3 locations in humidified and non humidified circuits during adult mechanical ventilation. AB - BACKGROUND: The position of the jet or ultrasonic nebulizer in the ventilator circuit impacts drug delivery during mechanical ventilation, but has not been extensively explored, and no study has examined all of the commonly used nebulizers. METHODS: Drug delivery from jet, vibrating-mesh, and ultrasonic nebulizers and pressurized metered-dose inhaler (pMDI) with spacer was compared in a model of adult mechanical ventilation, with heated/humidified and non humidified ventilator circuits. Albuterol sulfate was aerosolized at 3 circuit positions: (1) between the endotracheal tube and the Y-piece; (2) 15 cm from Y piece; and (3) 15 cm from the ventilator, with each device (n = 3) using adult settings (tidal volume 500 mL, ramp flow pattern, 15 breaths/min, peak inspiratory flow 60 L/min, and PEEP 5 cm H(2)O). The drug deposited on an absolute filter distal to an 8.0-mm inner-diameter endotracheal tube was eluted and analyzed via spectrophotometry (276 nm), and is reported as mean +/- SD percent of total nominal or emitted dose. RESULTS: The vibrating-mesh nebulizer, ultrasonic nebulizer, and pMDI with spacer were most efficient in position 2 with both non-humidified (30.2 +/- 1.0%, 24.7 +/- 4.4%, and 27.8 +/- 3.3%, respectively) and heated/humidified circuits (16.8 +/- 2.6%, 16.5 +/- 4.3%, and 17 +/- 1.0%, respectively). In contrast, the jet nebulizer was most efficient in position 3 under both non-humidified (14.7 +/- 1.5%) and heated/humidified (6.0 +/- 0.1%) conditions. In positions 2 and 3, all devices delivered approximately 2 fold more drug under non-humidified than under heated/humidified conditions (P < .01). At position 1 only the pMDI delivered substantially more drug than with the non-humidified circuit. CONCLUSION: During mechanical ventilation the optimal drug delivery efficiency depends on the aerosol generator, the ventilator circuit, and the aerosol generator position. PMID- 20587095 TI - Influence of nebulizer type, position, and bias flow on aerosol drug delivery in simulated pediatric and adult lung models during mechanical ventilation. AB - BACKGROUND: The effectiveness of aerosol drug delivery during mechanical ventilation is influenced by the patient, ventilator, and nebulizer variables. The impact of nebulizer type, position on the ventilator circuit, and bias flow on aerosol drug delivery has not been established for different age populations. OBJECTIVE: To determine the influence of nebulizer position and bias flow with a jet nebulizer and a vibrating-mesh nebulizer on aerosol drug delivery in simulated and mechanically ventilated pediatric and adult patients. METHOD: Albuterol sulfate (2.5 mg) was nebulized with a jet nebulizer and a vibrating mesh nebulizer, using simulated pediatric and adult lung models. The 2 nebulizer positions were: (1) jet nebulizer placed 15 cm from the Y-piece adapter, and vibrating-mesh nebulizer attached directly to the Y-piece; and (2) jet nebulizer placed prior to the heated humidifier with 15 cm of large-bore tubing, and vibrating-mesh nebulizer positioned at an inlet to the humidifier. A ventilator with a heated humidifier and ventilator circuit was utilized in both lung models. The adult ventilator settings were V(T) 500 mL, PEEP 5 cm H2O, respiratory rate 20 breaths/min, peak inspiratory flow 60 L/min, and descending ramp flow waveform. The pediatric ventilator settings were V(T) 100 mL, PEEP 5 cm H2O, respiratory rate 20 breaths/min, inspiratory time 1 s. We tested bias flows of 2 and 5 L/min. The adult and pediatric lung models used 8-mm and 5-mm inner diameter endotracheal tubes, respectively. Each experiment was run 3 times (n = 3). The albuterol sulfate was eluted from the filter and analyzed via spectrophotometry (276 nm). RESULTS: Nebulizer placement prior to the humidifier increased drug delivery with both the jet nebulizer and the vibrating-mesh nebulizer, with a greater increase with the vibrating-mesh nebulizer. Higher bias flow reduced drug delivery. Drug delivery with the vibrating-mesh nebulizer was 2 4-fold greater than with the jet nebulizer at all positions (P < .05) in both lung models. CONCLUSION: During simulated mechanical ventilation in pediatric and adult models, bias flow and nebulizer type and position impact aerosol drug delivery. PMID- 20587096 TI - Improvement in emergency airway equipment transport. AB - BACKGROUND: Airway management out of the operating room in many major institutions is often performed by teams, requiring airway providers to carry their own materials at all times. The bag containing airway equipment must be light enough to be carried easily, while containing sufficient equipment to manage airways in various settings. Additionally, transport of the bag throughout the hospital raises concern about transmission of infection. We hypothesized that a new system of multiple, smaller bags would decrease weight, facilitate prompt location of equipment, and reduce the risk of bags acting as fomites. METHODS: The service purchased small, nylon laryngoscope bags with dividers to keep equipment organized. The contents of the original bag and a new replacement bag were cataloged and both bags were weighed. Fourteen clinicians working on emergency airway consults at the time of the study were timed as they searched the bags for predetermined equipment with 2 scenarios and intubated a mannequin. The surfaces of the bags were swabbed for culture. RESULTS: Clinicians were significantly faster to locate equipment with the new compared to the original bag, with a difference of 39 s (P < .001, 95% CI 19-58 s) in the first scenario, and 22 s (P < .001, 95% CI 13-32 s) in the second. The cultures from the original bag demonstrated coagulase-negative Staphylococcus, enterococcus, Bacillus species, alpha-hemolytic Streptococcus, non-hemolytic Streptococcus, and a Staphylococcus species of a second type. The culture of the new bag after clinical use but before cleaning grew rare Aspergillosis species. The culture of the new bag after undergoing proper cleaning demonstrated no growth. CONCLUSIONS: Exchanging a large canvas bag for several smaller nylon bags has improved the transport of emergency airway equipment, with benefits in carrying the bag, locating equipment, and reducing the transport of pathogens throughout the hospital. PMID- 20587097 TI - An intervention to improve respiratory therapists' comfort with end-of-life care. AB - BACKGROUND: Respiratory therapists (RTs) are often involved in treating seriously ill and dying patients, but receive little instruction in end-of-life care. Prompted by several difficult cases, we developed an interdisciplinary program to introduce practicing RTs to ethical and end-of-life issues, and evaluated the program with a dedicated survey instrument. METHODS: A convenience sample of RTs from a university hospital and nearby community hospitals participated in a one day interactive program, in 2005 (n = 49) and in 2008 (n = 36), that included role-play and didactic components. The questionnaire completed before and after the program included scales on comfort with end-of-life care and role in end-of life care, and knowledge indices. RESULTS: Nearly all the RTs had recently encountered end-of-life situations, yet most had not received dedicated training and felt ill-prepared to deal with these situations; one third reported distress related to withdrawal of treatment. The 78 participants who completed both the before and after surveys had increased comfort with end-of-life care (P < .001) and their perception of their role in end-of-life care (P < .001). Knowledge about end-of-life care also increased (P < .001). CONCLUSIONS: A one-day interactive educational intervention can improve short-term RT comfort and role perception concerning end-of-life care. Evaluation of longer-term clinical outcomes and implementation in other venues is needed. PMID- 20587098 TI - The short-term effects of intermittent positive pressure breathing treatments on ventilation in patients with neuromuscular disease. AB - BACKGROUND: The effects of intermittent positive-pressure breathing (IPPB) and abdominal belt on regional lung ventilation in neuromuscular patients are unknown. We conducted a prospective physiologic short-term study in stable neuromuscular patients to determine the effects of IPBB, with and without abdominal belt, on regional lung ventilation. METHODS: IPPB was performed as 30 consecutive deep breaths up to 30 cm H(2)O face-mask pressure each: 10 in supine position, 10 in left-lateral position, and 10 in right-lateral position. Each patient received IPPB sessions with and without an abdominal belt, in a random order, at one-day intervals. Patients were then followed-up to 3 hours after IPPB. Lung ventilation was measured via electrical-impedance tomography (tidal volume via electrical-impedance tomography [electrical-impedance V(T)], which is reported in arbitrary units) in 4 lung quadrants. Baseline V(T) and exhaled V(T) after each deep breath were also measured. The primary outcome was maintenance of regional ventilation after 3 hours. RESULTS: Global electrical-impedance V(T) remained significantly higher than at baseline as long as 3 hours after the IPPB sessions. Global and regional electrical-impedance V(T) at the end of the 3-hour study period was significantly higher with the abdominal belt in place. Regional ventilation did not change significantly. With IPPB in the supine position, electrical-impedance V(T) was significantly greater in the anterior than the posterior lung regions (P < .001). With IPPB in supine position, median and interquartile range V(T) values increased from 0.25 L (0.20-0.30) to the exhaled V(T) of 1.50 L (1.08-1.96) (P < .001). There were no differences in regional ventilation. CONCLUSIONS: In patients with neuromuscular disease, supine IPPB treatments, with or without abdominal belt, increased ventilation to anterior lungs regions, compared to the left-lateral and right-lateral positions. Global ventilation 3 hours after IPPB treatments remained higher than at baseline and was best preserved with the use of an abdominal belt. PMID- 20587099 TI - Four-year calibration stability of the EasyOne portable spirometer. AB - BACKGROUND: Clinical practice guidelines recommend daily spirometer calibration checks and weekly linearity checks. The long-term stability of the volume and flow accuracy of a specific model of spirometer should be carefully characterized before modification of the frequency of calibration checks is considered for that model of spirometer. METHODS: The EasyOne ultrasonic flow-sensing spirometer was chosen for use by the clinical centers at the 2002 inception of the World Trade Center Worker and Volunteer Medical Screening Program. The screening program quality-control procedure required that the expiratory and inspiratory volume accuracy of each spirometer be checked every day of testing, and the flow accuracy (linearity) checked every week. The calibration check results were transferred to a central database for summary. RESULTS: Over 5,000 calibration check results (4,109 single-speed and 1,189 three-speed) were accumulated from a total of 34 spirometers during the period February 2003 through March 2007. The mean single-speed calibration errors (and 5th-95th percentiles) were -2 mL (-80 to 70 mL) for exhalation and -10 mL (-80 to 60 mL) for inhalation. 98% of the exhalation and 97% of the inhalation calibration checks were accurate within 3.0%. There was no evidence of significant non-linearity according to the results of the 3-speed calibration checks (mean errors of -3, -5, and -6 mL at each speed). CONCLUSIONS: The EasyOne retained inhalation and exhalation volume accuracy of better than 3% for at least 4 years. Routine multiple-speed volume calibration checks may not be necessary with the EasyOne. The acceptability and repeatability of patient efforts should be the primary focus of quality-assurance programs with spirometers that have been demonstrated to remain accurate for long periods. PMID- 20587100 TI - Effects of inspiratory rise time on triggering work load during pressure-support ventilation: a lung model study. AB - BACKGROUND: The rise in inspiratory flow is important during patient-triggered ventilation. Many ventilators incorporate a function to control the time to reach the targeted airway pressure (inspiratory rise time). However, it has not been clarified how inspiratory rise time affects inspiratory work load under various ventilator settings. In a bench study we investigated the effect of inspiratory rise time on inspiratory work load during pressure-support ventilation (PSV). METHODS: We studied 6 ICU ventilators. We measured flow and pressure at the airway opening (P(ao)) at PEEP of 5 cm H(2)O, pressure-support of 5 cm H(2)O and 10 cm H(2)O, 4 triggering sensitivities, and inspiratory drives 300 mL, 500 mL, and 700 mL. The inspiratory-rise-time setting was not consistent between the ventilators, and we chose 3 inspiratory-rise-time levels with each ventilator. The inspiratory delay time (DT) was defined as the time between the onset of inspiration and the return of P(ao) to baseline, and was divided into 2 parts at the point of the lowest P(ao): before the lowest P(ao) (DT(1)), and after the lowest P(ao) (DT(2)). As an indicator of inspiratory work load we calculated the pressure-time-product (PTP) of the P(ao) over the DT. PTP was also divided into PTP(1) and PTP(2), at the point of the lowest P(ao). RESULTS: Short inspiratory rise time reduced DT(2), PTP(1), and PTP(2), regardless of the pressure-support level, triggering sensitivity, or inspiratory drive. However, the inspiratory rise-time setting did not affect DT(1). The PTP(1), PTP(2), and DT(2) values differed significantly among the ventilators. A combination of short inspiratory rise time, high PSV, and sharp triggering sensitivity resulted in the smallest PTP and DT values. CONCLUSIONS: Short inspiratory rise time decreased inspiratory work load, regardless of the pressure-support level, triggering sensitivity, or inspiratory drive. Inspiratory work load can be maximally lowered by a combination of a short inspiratory rise time, a sharp triggering sensitivity, and a high inspiratory pressure-support level for a given patient's inspiratory effort. PMID- 20587101 TI - Adjuncts to physical training of patients with severe COPD: oxygen or noninvasive ventilation? AB - BACKGROUND: Previous studies have shown positive effects from noninvasive ventilation (NIV) or supplemental oxygen on exercise capacity in patients with COPD. However, the best adjunct for promoting physiologic adaptations to physical training in patients with severe COPD remains to be investigated. METHODS: Twenty eight patients (mean +/- SD age 68 +/- 7 y) with stable COPD (FEV(1) 34 +/- 9% of predicted) undergoing an exercise training program were randomized to either NIV (n = 14) or supplemental oxygen (n = 14) during group training to maintain peripheral oxygen saturation (S(pO2)) >/= 90%. Physical training consisted of treadmill walking (at 70% of maximal speed) 3 times a week, for 6 weeks. Patients were assessed at baseline and after 6 weeks. Assessments included physiological adaptations during incremental exercise testing (ratio of lactate concentration to walk speed, oxygen uptake [V (O2)], and dyspnea), exercise tolerance during 6 min walk test, leg fatigue, maximum inspiratory pressure, and health-related quality of life. RESULTS: Two patients in each group dropped out due to COPD exacerbations and lack of exercise program adherence, and 24 completed the training program. Both groups improved 6-min walk distance, symptoms, and health related quality of life. However, there were significant differences between the NIV and supplemental-oxygen groups in lactate/speed ratio (33% vs -4%), maximum inspiratory pressure (80% vs 23%), 6-min walk distance (122 m vs 47 m), and leg fatigue (25% vs 11%). In addition, changes in S(pO2)/speed, V (O2), and dyspnea were greater with NIV than with supplemental-oxygen. CONCLUSIONS: NIV alone is better than supplemental oxygen alone in promoting beneficial physiologic adaptations to physical exercise in patients with severe COPD. PMID- 20587102 TI - Occupational exposures and obstructive lung disease: a case-control study in hairdressers. AB - BACKGROUND: Hairdressers are exposed to various irritating chemicals during work. OBJECTIVE: This study was designed as a case-control study to evaluate the risk of developing obstructive lung disease in relation to occupational exposures in hairdressers. METHODS: We interviewed a cohort of 50 female hairdressers and 50 matched controls recruited from a random sample of the general population, using a validated questionnaire for occupational respiratory disease, to compare the prevalence of work-initiated and work-related respiratory symptoms in both groups. We also performed pulmonary function tests (PFTs) in all participants. RESULTS: Almost half of the hairdressers reported work-initiated respiratory symptoms. Cough (33%) and breathlessness (29%) were the most common self-reported symptoms after chemical exposures. All respiratory symptoms (cough, breathless, wheezing, and phlegm) were significantly higher in the hairdressers than in the control group (P < .001). The hairdressers reported that bleaching powder and hair spray were the most irritant chemicals that provoke their respiratory symptoms. The impaired PFT values (forced vital capacity, FEV(1), maximum mid expiratory flow, peak expiratory flow) in the hairdressers, compared to the matched controls, were in line with the questionnaire data. CONCLUSIONS: Hairdressing work is associated with a high frequency of work-initiated respiratory symptoms and, to a lesser extent, with allergic symptoms, particularly after exposure to bleaching powder and hair spray. PFT values were significantly lower among the hairdressers, which might be a predictor for developing obstructive lung disease. PMID- 20587103 TI - Prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C: a systematic review and meta-analysis. AB - BACKGROUND: Activated protein C reduces 28-day mortality in patients with severe sepsis, but its anticoagulant properties entail a risk of bleeding. OBJECTIVE: The aim of this systematic review was to evaluate the prevalence of serious bleeding events in patients receiving activated protein C. METHODS: We searched the MEDLINE and EMBASE databases for studies that described the prevalence of serious bleeding events and intracranial hemorrhage in patients receiving activated protein C. We calculated the bleeding rates by calculating proportions and 95% CIs for each study, and then pooled the data to derive a pooled proportion and 95% CI. RESULTS: Our search yielded 17 studies, which included 10,679 patients. The occurrence of serious bleeding events in patients receiving activated protein C ranged from 0.5% to 9.6%, and the pooled prevalence was 3.3% (95% CI 2.4-4.4%) by the random effects model. The occurrence of intracranial hemorrhage ranged from 0% to 1.4%, and the pooled prevalence was 0.44% (95% CI 0.31-0.6%). Sensitivity analysis showed a higher prevalence of bleeding in the observational studies than in the randomized controlled trials. There was substantial clinical and statistical heterogeneity, but no evidence of publication bias. CONCLUSIONS: Activated protein C is associated with significant risk of bleeding, so strict inclusion and exclusion criteria should be set prior to administering activated protein C. PMID- 20587104 TI - Air and soul: the science and application of aerosol therapy. AB - This paper reviews the history of aerosol therapy; discusses patient, drug, and device factors that can influence the success of aerosol therapy; and identifies trends that will drive the science of aerosol therapy in the future. Aerosol medication is generally less expensive, works more rapidly, and produces fewer side effects than the same drug given systemically. Aerosol therapy has been used for thousands of years by steaming and burning plant material. In the 50 years since the invention of the pressurized metered-dose inhaler, advances in drugs and devices have made aerosols the most commonly used way to deliver therapy for asthma and COPD. The requirements for aerosol therapy depend on the target site of action and the underlying disease. Medication to treat airways disease should deposit on the conducting airways. Effective deposition of airway particles generally requires particle size between 0.5 and 5 microm mass median aerodynamic diameter; however, a smaller particle size neither equates to greater side effects nor greater effectiveness. However, medications like peptides intended for systemic absorption, need to deposit on the alveolar capillary bed. Thus ultrafine particles, a slow inhalation, and relatively normal airways that do not hinder aerosol penetration will optimize systemic delivery. Aerosolized antimicrobials are often used for the treatment of cystic fibrosis or bronchiectasis, and mucoactive agents to promote mucus clearance have been delivered by aerosol. As technology improves, a greater variety of novel medications are being developed for aerosol delivery, including for therapy of pulmonary hypertension, as vaccines, for decreasing dyspnea, to treat airway inflammation, for migraine headache, for nicotine and drug addiction, and ultimately for gene therapy. Common reasons for therapeutic failure of aerosol medications include the use of inactive or depleted medications, inappropriate use of the aerosol device, and, most importantly, poor adherence to prescribed therapy. The respiratory therapist plays a key role in patient education, device selection, and outcomes assessment. PMID- 20587105 TI - Patient safety, quality of care, and knowledge translation in the intensive care unit. AB - A large gap exists between the completion of clinical research demonstrating the benefit of new treatment interventions and improved patient outcomes resulting from implementation of these interventions as part of routine clinical practice. This gap clearly affects patient safety and quality of care. Knowledge translation is important for addressing this gap, but evaluation of the most appropriate and effective knowledge translation methods is still ongoing. Through describing one model for knowledge translation and an example of its implementation, insights can be gained into systematic methods for advancing the implementation of evidence-based interventions to improve safety, quality, and patient outcomes. PMID- 20587106 TI - Solitary primary tracheal small-cell lung cancer causing acute respiratory failure: diagnosis and treatment. AB - Small-cell lung cancer often presents as an extensive cancer, and rarely as a solitary tracheal tumor. We report a 41-year-old male smoker with dyspnea and wheezing that was initially diagnosed as asthma and treated with bronchodilators. He was later intubated for acute respiratory failure, and computed tomography revealed a tracheal mass. Solitary primary small-cell lung cancer was diagnosed via bronchoscopic biopsy. The patient received bronchoscopic electro-surgery and was successfully extubated. Concurrent chemo-radiotherapy was performed due to the stage IV small-cell lung cancer. PMID- 20587107 TI - A 65-year-old man with an endobronchial gossypiboma after lobectomy for abscessing pneumonia. AB - We present a case of a 65-year-old man with recurrent hemoptysis and weight loss for 6 months. Thirty-two years earlier, lobectomy of the right lower lobe had been performed for abcessing pneumonia. Due to recurrent pulmonary infections after lobectomy the patient had to retire at the age of 46. A diagnostic procedure to explain the hemoptysis was performed. A computed tomogram revealed a suspicious formation in the bronchus intermedius, and the patient was referred to our department with the suspicion of lung cancer. During bronchoscopy an endobronchial mass was detected and extracted whole with a foreign-body forceps. Textile fibers of a sponge in the histology specimen led to the final diagnosis of gossypiboma (also known as textiloma). After removal of the gossypiboma no further pulmonary infections occurred. PMID- 20587108 TI - A case of pulmonary cryptococcosis caused by capsule-deficient cryptococcus neoformans in an immunocompetent patient. PMID- 20587109 TI - Clearing the mist from our eyes: bronchodilators, mechanical ventilation, new devices, locations, and what you should know about bias flow. PMID- 20587110 TI - The defenseless tracheal conduit: can a team work together to improve airway protection? PMID- 20587111 TI - Finding comfort in end-of-life care. PMID- 20587112 TI - Is humidification always necessary during noninvasive ventilation in the hospital? PMID- 20587113 TI - Efficacy of combined treatment with albendazole and baicalein against eosinophilic meningitis induced by Angiostrongylus cantonensis in mice. AB - Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis. PMID- 20587114 TI - Relationship of serum carotenoids and retinol with anaemia among pre-school children in the northern mountainous region of Vietnam. AB - OBJECTIVE: To characterize the relationship between serum carotenoids, retinol and anaemia among pre-school children. DESIGN: A cross-sectional study was conducted in two groups: anaemic and non-anaemic. Serum levels of retinol, alpha carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein and zeaxanthin were measured in the study subjects. SETTING: Six rural communes of Dinh Hoa, a rural and mountainous district in Thai Nguyen Province, in the northern mountainous region of Vietnam. SUBJECTS: A total of 682 pre-school children, aged 12-72 months, were recruited. RESULTS: Geometric mean serum concentrations of carotenoids (MUmol/l) were 0.056 for alpha-carotene, 0.161 for beta-carotene, 0.145 for beta-cryptoxanthin, 0.078 for lycopene, 0.388 for lutein and 0.075 for zeaxanthin. The mean levels of Hb and serum retinol were 108.8 g/l and 1.02 MUmol/l, respectively. The prevalence of anaemia and vitamin A deficiency was 53.7 % and 7.8 %, respectively. After adjusting for sex and stunting, serum retinol concentrations (MUmol/l; OR = 2.06, 95 % CI 1.10, 3.86, P = 0.024) and total provitamin A carotenoids (MUmol/l; OR = 1.52, 95 % CI 1.01, 2.28, P = 0.046) were independently associated with anaemia, but non-provitamin A carotenoids (MUmol/l; OR = 0.93, 95 % CI 0.63, 1.37, P = 0.710) were not associated with anaemia. CONCLUSIONS: Among pre-school children in the northern mountainous region of Vietnam, the prevalences of vitamin A deficiency and anaemia are high, and serum retinol and provitamin A carotenoids are independently associated with anaemia. Further studies are needed to determine if increased consumption of provitamin A carotenoids will reduce anaemia among pre school children. PMID- 20587115 TI - The duration of obesity and the risk of type 2 diabetes. AB - OBJECTIVE: The evidence for the association between obesity and the risk of type 2 diabetes has been derived mainly from the analysis of the degree of obesity. The role of the duration of obesity as an independent risk has not been fully explored. The objective of the present study was to investigate the association between the duration of obesity and the risk of type 2 diabetes. DESIGN: Prospective cohort study. SETTING: The Framingham Heart Study (FHS), follow-up from 1948 to 1998. SUBJECTS: A total of 1256 FHS participants who were free from type 2 diabetes at baseline, but were obese on at least two consecutive of the study's twenty-four biennial examinations, were included. Type 2 diabetes status was collected throughout the 48 years of follow-up of the study. The relationship between duration of obesity and type 2 diabetes was analysed using time-dependent Cox models, adjusting for a number of covariates. RESULTS: The unadjusted hazard ratio (HR) for the risk of type 2 diabetes for men was 1.13 (95 % CI 1.09, 1.17) and for women was 1.12 (95 % CI 1.08, 1.16) per additional 2-year increase in the duration of obesity. Adjustment for sociodemographic variables, family history of diabetes, health behaviour and physical activity made little difference to these HR. For women the evidence of a dose-response relationship was less clear than for men, particularly for women with an older age at obesity onset. CONCLUSIONS: The duration of obesity is a relevant risk factor for type 2 diabetes, independent of the degree of BMI. PMID- 20587116 TI - Infant feeding practices among HIV-positive women in Dar es Salaam, Tanzania, indicate a need for more intensive infant feeding counselling. AB - OBJECTIVE: To assess feeding practices of infants born to HIV-positive women in Dar es Salaam, Tanzania. These data then served as a proxy to evaluate the adequacy of current infant feeding counselling. DESIGN: A cross-sectional survey of infant feeding behaviours. SETTING: Four clinics in greater Dar es Salaam in early 2008. SUBJECTS: A total of 196 HIV-positive mothers of children aged 6-10 months recruited from HIV clinics. RESULTS: Initiation of breast-feeding was reported by 95.4 % of survey participants. In the entire sample, 80.1 %, 34.2 % and 13.3 % of women reported exclusive breast-feeding (EBF) up to 2, 4 and 6 months, respectively. Median duration of EBF among women who ever breast-fed was 3 (interquartile range (IQR): 2.1, 4.0) months. Most non-breast-milk foods fed to infants were low in nutrient density. Complete cessation of breast-feeding occurred within 14 d of the introduction of non-breast-milk foods among 138 of the 187 children (73.8 %) who had ever received any breast milk. Of the 187 infants in the study who ever received breast milk, 19.4 % received neither human milk nor any replacement milks for 1 week or more (median duration of no milk was 14 (IQR: 7, 152) d). CONCLUSIONS: Infant feeding practices among these HIV positive mothers resulted in infants receiving far less breast milk and more mixed complementary feeds than recommended, thus placing them at greater risk of both malnutrition and HIV infection. An environment that better enables mothers to follow national guidelines is urgently needed. More intensive infant feeding counselling programmes would very likely increase rates of optimal infant feeding. PMID- 20587117 TI - Lifetime health outcomes of breast-feeding: a comparison of the policy documents of five European countries. AB - OBJECTIVE: To (i) identify and describe prevailing infant feeding policy documents in five diverse European countries; (ii) analyse types of health outcomes for the infant that are associated with feeding breast milk rather than formula milk in the documents of different countries; and (iii) assess the extent to which documents reflect the WHO global recommendation of exclusive breast feeding for 6 months. DESIGN: Documentary review and analysis. SETTING: Five geographically dispersed countries of Europe (England, Finland, Germany, Hungary and Spain). SUBJECTS: Policy documents on infant feeding were identified; statements that linked choice between breast- and formula-feeding to a health outcome for the infant were extracted. RESULTS: Twenty-six documents (varied authorships, dates, length and character) were identified: four from England; two from Finland; nine from Germany; six from Hungary; and five from Spain. There was no consistency in the way in which health outcomes were cited as factors in the recommendations for breast- rather than formula-feeding. Seven documents contained no reference to the health implications of infant feeding choice. Of 203 statements in remaining documents citing health outcomes, 24.1 % mentioned general health effects, 32.5 % protection against infections, 31.5 % long-term conditions (e.g. diabetes, CVD) and 11.8 % mentioned allergy. Health outcomes were linked to exclusive breast-feeding in only 25 % of statements. CONCLUSIONS: Policy documents in the study countries varied in the extent to which they reflect the health outcomes for the baby of breast-feeding, and this may limit effective promotion by health professionals. There is scope to improve the process of bringing evidence and recommendations into policy documents. PMID- 20587118 TI - Excess morbidity in the hepatitis C-diagnosed population in Scotland, 1991-2006. AB - We estimated the excess risk of in-patient hospitalization in a large cohort of persons diagnosed with hepatitis C virus (HCV) infection, controlling for social deprivation. A total of 20 749 individuals diagnosed with HCV in Scotland by 31 December 2006 were linked to the Scottish hospital discharge database, and indirectly standardized hospitalization rates, adjusting for sex, age, year and deprivation were calculated. We observed significant excess morbidity considering episodes for: any diagnosis [standardized morbidity ratio (SMR) 3.4, 95% CI 3.3 3.5]; liver-related diagnoses (SMR 41.3, 95% CI 39.6-43.0); and only non-liver related diagnoses (SMR 2.14, 95% CI 2.08-2.19). Cox regression analyses of the 2000-2006 data indicated increased relative risks of hospitalization for males [hazard ratio (HR) 1.1, 95% CI 1.0-1.2], older age (per 10 years) (HR 1.55, 95% CI 1.5-1.6), and those testing HIV-positive (HR 1.6, 95% CI 1.3-1.8). This study has revealed substantial excess all-cause and liver-related morbidity in the Scottish HCV-diagnosed population, even after allowing for deprivation. PMID- 20587119 TI - An outbreak of hepatitis A affecting a nursery school and a primary school. AB - Between March and June 2008, 12 cases of hepatitis A were notified in Winchester. Cases were from a primary school and a nursery school with no direct linkage. Hepatitis A virus (HAV) RNA sequenced from nine cases confirmed the strain in both schools to be identical. The outbreak could have affected three other schools and a maternity unit and was controlled by immunization and screening of neonates in the maternity unit by dried blood spots. No neonates were infected and no further cases were reported until 5 months later when the index case's mother became infected with same strain of virus associated with the outbreak despite vaccination. Neither the source of the outbreak or the subsequent infection of the index case's mother was identified; however, with the timing of the cases continued transmission in the community by children with asymptomatic infection or a recurrent source cannot be ruled out. PMID- 20587120 TI - Putative household outbreaks of campylobacteriosis typically comprise single MLST genotypes. AB - During a 15-month period in Scotland a small but important number of human Campylobacter cases (3.2%) arose from 91 putative household outbreaks. Of the 26 outbreaks with known strain composition, 89% were composed of the same MLST which supports the potential use of MLST in public health epidemiology. The number of cases associated with household outbreaks is much larger than general outbreaks and there is some evidence to indicate that there may be secondary transmission, although this is relatively rare. PMID- 20587121 TI - Effect on seroprevalence of anti-poliovirus antibodies and on vaccination coverage of the implementation of a DTwP-IPV-Hib vaccination programme in a South American city. AB - Vaccination coverage and seroprevalence of poliovirus antibodies were assessed in Argentinean children (aged 8-12 and 19-21 months) living in Cordoba City pre /post-implementation of a DTwP-IPV-Hib vaccination programme, and compared to those of controls from neighbouring populations receiving a full oral poliovirus vaccine schedule. Vaccination coverage was higher in control areas pre intervention; this increased post-intervention in Cordoba (>90%) but not in control areas. Poliovirus types 1 and 2 seroprotection rates were >97% in all groups pre-/post-intervention. Type 3 seroprotection rates were generally lower, but increased post-intervention in Cordoba becoming significantly higher than control rates. Anti-type 1 and 3 antibody titres increased twofold and sevenfold, respectively, post-intervention, whereas anti-type 2 antibody titres decreased ~40% in the 8-12 months group. All titres increased in the 19-21 months post intervention group. The introduction of a three-dose primary DTwP-IPV-Hib schedule maintained protection against poliovirus types 1 and 2, and increased protection against type 3, while vaccine coverage in the study area increased. PMID- 20587122 TI - Risk factors for ceftiofur resistance in Escherichia coli from Belgian broilers. AB - A cross-sectional study on 32 different Belgian broiler farms was performed in 2007 and 2008 to identify risk factors for ceftiofur resistance in Escherichia coli. On each farm, one E. coli colony was isolated from 30 random birds. Following susceptibility testing of 14 antimicrobials, an on-farm questionnaire was used to obtain information on risk factors. Using a multilevel logistic regression model two factors were identified at the animal level: resistance to amoxicillin and to trimethoprim-sulfonamide. On the farm level, besides antimicrobial use, seven management factors were found to be associated with the occurrence of ceftiofur resistance in E. coli from broilers: poor hygienic condition of the medicinal treatment reservoir, no acidification of drinking water, more than three feed changes during the production cycle, hatchery of origin, breed, litter material used, and treatment with amoxicillin. This study confirms that not only on-farm antimicrobial therapy, but also management- and hatchery-related factors influence the occurrence of antimicrobial resistance. PMID- 20587123 TI - Are we hitting immunity targets? The 2006 age-specific seroprevalence of measles, mumps, rubella, diphtheria and tetanus in Belgium. AB - Susceptibility to vaccine-preventable diseases in Belgium in 2006 was estimated from a serum survey. Immunoglobulins against measles, mumps, rubella (MMR) and diphtheria at all available ages (1-65 years), and against tetanus in >40-year olds, were measured by ELISA. Age-standardized overall seronegativity for MMR was low (3.9%, 8.0%, 10.4%, respectively). However, the World Health Organization's targets for measles elimination were not met in 5- to 24-year-olds and about 1 in 7 women at childbearing age (15-39 years) were seronegative for rubella. In adults >40 years, tetanus immunity (87.2%, >0.16 IU/ml) largely exceeded diphtheria immunity (20-45%, >0.1 IU/ml). Despite free universal vaccination against MMR for more than 20 years and against diphtheria and tetanus for almost 60 years, our study revealed specific age groups remaining at risk for infection with these pathogens. PMID- 20587124 TI - Quantitative analysis of epidemic and population patterns in the Chinese Empire: how is this possible ? PMID- 20587125 TI - Using the internet for rapid investigation of an outbreak of diarrhoeal illness in mountain bikers. AB - In summer 2008, we investigated an outbreak of diarrhoeal illness in participants of a mountain-bike event in Wales (UK) which had been affected by heavy rain. We conducted a retrospective cohort study to investigate the cause using an internet based questionnaire. Fifty-three percent of those contacted responded, and 161 (46.5%) out of the 347 responders, reported gastrointestinal symptoms. Median day of onset was 3 days following the event. Ten riders reported receiving a laboratory-confirmed diagnosis of Campylobacter. Multivariate logistic regression analysis identified the inadvertent ingestion of mud (OR 2.5, 95% CI 1.5-4.2, P<0.001) and eating 'other' food during the event (OR 2.1, 95% CI 1.2-3.6, P=0.01) as significant risk factors for illness. We concluded that the outbreak was caused by Campylobacter, spread to the riders by the inadvertent ingestion of mud which had been contaminated with sheep faeces from the rural course. Mountain bike race organizers should consider microbiological hazards when risk-assessing potential race courses. The internet is an efficient tool for the investigation of outbreaks in computer-literate populations. PMID- 20587126 TI - Giardiasis outbreak at a camp after installation of a slow-sand filtration water treatment system. AB - In July and August 2007, a giardiasis outbreak affected attendees of a private recreational camp in California. Twenty-six persons had laboratory-confirmed giardiasis; another 24 had giardiasis-like illness with no stool test. A retrospective cohort study determined that showering was associated with illness (adjusted odds ratio 3.1, 95% confidence interval 1.1-9.3). Two days before the outbreak began, the camp had installed a slow-sand water filtration system that included unsterilized sand. Review of historical water-quality data identified substantially elevated total coliform and turbidity levels in sand-filtered spring water used for showering during the suspected exposure period. Unfiltered spring water tested at the same time had acceptable coliform and turbidity levels, implicating the filtration system as the most likely contamination source. To prevent waterborne illness, slow-sand water filtration systems should use sterilized sand, and slow-sand-filtered water should not be used for any purpose where inadvertent ingestion could occur until testing confirms its potability. PMID- 20587127 TI - Evaluation of crude hydatid cyst fluid antigens for the serological diagnosis of hydatidosis in cattle. AB - Echinococcosis is a zoonotic infection caused by adult or larval (metacestode) stages of cestodes belonging to the genus Echinococcus. The purpose of this study was to evaluate the antigenic ability of hydatid cyst fluid antigen for the diagnosis of hydatidosis in cattle using enzyme-linked immunosorbent assay (ELISA) and indirect haemagglutination test (IHA). The source of the antigens for the serological tests was fertile crude cyst fluids collected from naturally infected sheep at the Addis Ababa abattoir. A total of 502 sera were collected from 329 uninfected cattle and 173 hydatid-infected cattle which were confirmed by post-mortem examination. Most cysts were sterile and multiple organ infection predominated. Of 173 infected cattle, 166 (96.0%; confidence interval (CI) 91.8 98.4) were positive using ELISA while 7 (4.0%) were negative. Of 329 sera from uninfected cattle, 274 (83.3%; CI 78.8-87.2) were found to be negative and the remaining 55 (16.7%) were positive by ELISA. Of 173 infected cattle, 151 (87.3%; CI 81.4-91.9) were positive and 22 (12.7%) were negative by IHA. Of 329 negative sera tested using IHA, 266 (80.9%; CI 76.2-85.0) were negative and the remaining 63 (19.1%) were positive. The false positive and negative values of ELISA were 4.0 and 16.7%, respectively, and the corresponding values of IHA were 12.7 and 19.1%. The sensitivity and diagnostic efficiency of IHA were 87.2 and 83.6%, respectively. Crude hydatid cyst fluid antigen seems to have reasonable antigenic properties and hence could be employed for epidemiological surveillance of cattle hydatidosis. PMID- 20587128 TI - Allergic disease: understanding how in utero events set the scene. AB - Events and exposures in pregnancy can have critical effects on fetal development with lasting implications for subsequent health and disease susceptibility. There is growing interest in how modern environmental changes influence fetal immune development and contribute to the recent epidemic of allergy and other immune disorders. Rising rates of allergic disease in early infancy, together with pre symptomatic differences in immune function at birth, suggest that antenatal events play a predisposing role in the development of disease. A number of environmental exposures in pregnancy can modify neonatal immune function including diet, microbial exposure and maternal smoking, and there is emerging evidence from animal models that these factors may have epigenetic effects on immune gene expression and disease susceptibility. Furthermore, functional genetic polymorphisms also alter individual vulnerability to the effects of these environmental exposures, highlighting the complexity of gene-environmental interactions in this period. All these observations underscore the need for ongoing research to understand the pathogenesis and rising incidence of disease in the hope of better strategies to reverse this. PMID- 20587129 TI - Increased sensitivity for angry faces in depressive disorder following 2 weeks of 2-Hz repetitive transcranial magnetic stimulation to the right parietal cortex. AB - According to the cognitive neuropsychological hypothesis of antidepressant action, the onset of subjectively experienced therapeutic effects to treatment is preceded by favourable changes in psychological functioning that can be measured by implicit methods. The aim of this study was to examine additional data to explore this hypothesis in an intention-to-treat repetitive transcranial magnetic stimulation (rTMS) study targeting the right parietal cortex. Changes in depression scores from baseline and the sensitivity for recognizing emotional facial expressions were studied in 28 patients with depressive disorder receiving ten sessions of real (n=14) or sham (n=14) rTMS treatments in a double-blind, sham-controlled design. In the patient group results showed significantly higher sensitivity for recognizing angry facial expressions in response to receiving real compared to receiving sham rTMS treatment. Overall mood improvement was similar across real and sham rTMS treatments. However, the sensitivity for recognizing angry facial expressions was correlated to the percentage decrease in depression scores. These results provide the first preliminary support for the cognitive neuropsychological hypothesis of antidepressant action in rTMS treatment. PMID- 20587130 TI - Hypothalamic orexin and pro-opiomelanocortin activities are essential for the anorexic effects of m-chlorophenylpiperazine in mice. AB - Hypothalamic pro-opiomelanocortin (POMC) activity is reportedly essential for satiety signalling downstream of serotonin (5-HT). Here we show that food restricted wild-type mice, which exhibited decreased hypothalamic POMC expression and increased hypothalamic orexin expression, were responsive to m chlorophenylpiperazine (m-CPP), a 5-HT(2C/1B) receptor agonist, leading to anorexia, whereas food-restricted A(y) mice with decreased hypothalamic POMC and orexin expression, were not. Injection of POMC small interfering RNA (siRNA) oligonucleotide+orexin siRNA oligonucleotide into the third cerebral ventricle was unresponsive to mCPP-induced anorexia, whereas a single injection of POMC or orexin siRNA oligonucleotides elicited a response. The injection of POMC siRNA oligonucleotides suppressed the anorexic effects of sibutramine, a serotonin and noradrenaline re-uptake inhibitor. The injection of orexin siRNA oligonucleotides suppressed the hyperphagia induced by the injection of POMC siRNA oligonucleotides. These findings suggest that functional hypothalamic POMC and orexin activity has a critical role in satiety signalling of mCPP in mice. PMID- 20587131 TI - Cannabinoid CB1 receptors in the medial prefrontal cortex modulate the expression of contextual fear conditioning. AB - The ventral portion of the medial prefrontal cortex (vMPFC) has been related to the expression of contextual fear conditioning. This study investigated the possible involvement of CB1 receptors in this aversive response. Male Wistar rats were submitted to a contextual aversive conditioning session and 48 h later re exposed to the aversive context in which freezing and cardiovascular responses (increase of arterial pressure and heart rate) were recorded. The expression of CB1 receptor-mRNA in the vMPFC was also measured using real time-PCR. In the first experiment intra-vMPFC administration of the CB1 receptor agonist anandamide (AEA, 5 pmol/200 nl) or the AEA transport inhibitor AM404 (50 pmol/200 nl) prior to re-exposure to the aversive context attenuated the fear-conditioned responses. These effects were prevented by local pretreatment with the CB1 receptor antagonist AM251 (100 pmol/200 nl). Using the same conditioning protocol in another animal group, we observed that CB1 receptor mRNA expression increased in the vMPFC 48 h after the conditioning session. Although AM251 did not cause any effect by itself in the first experiment, this drug facilitated freezing and cardiovascular responses when the conditioning session employed a lesser aversive condition. These results indicated that facilitation of cannabinoid-mediated neurotransmission in the vMPFC by local CB1 receptor activation attenuates the expression of contextual fear responses. Together they suggest that local endocannabinoid-mediated neurotransmission in the vMPFC can modulate these responses. PMID- 20587132 TI - Nutritional profile of schoolchildren from different socio-economic levels in Santiago, Chile. AB - OBJECTIVE: To assess the nutritional status, food intake and physical activity patterns in schoolchildren attending 5th and 6th grade in basic schools from different socio-economic levels in the metropolitan region of Santiago. DESIGN: Cross-sectional study in children 5th and 6th grade of eighteen basic schools in the metropolitan region of Santiago. SETTING: Boys and girls aged 9-12 years from basic schools were evaluated in terms of physical capacity. An anthropometric evaluation was also performed which included weight, height and triceps and subscapular skinfold thicknesses. Food intake was evaluated by a 24 h recall, socio-economic level by the ESOMAR method and physical activity by a questionnaire. SUBJECTS: Boys and girls aged 9-12 years (n 1732). RESULTS: The average prevalence of overweight and obesity was 40 %, with the highest prevalence in males and those from lower socio-economic level. A majority (64 %) of the children had a low level of physical activity. A higher intake of fat and protein and a higher intake of carbohydrate were found in the higher and lower socio-economic levels, respectively. Both males and females showed adequacy greater than 75 % in macronutrient intake except for fibre, with both groups showing a deficit in the consumption of fruits, vegetables, legumes, fish and milk products according to Chilean recommendations. CONCLUSIONS: A high prevalence of malnutrition by excess was observed in both sexes and a better eating and physical activity pattern was seen in children from higher socio economic level. PMID- 20587133 TI - Pressure injection demonstrates points of weakness in the posterior nasal arteries. PMID- 20587134 TI - Stability of housekeeping genes and expression of locally produced growth factors and hormone receptors in goat preantral follicles. AB - The aim of the present study was to investigate the stability of six housekeeping genes, and the relative expression of growth factors (EGF, GDF-9, BMP-15, VEGF, FGF-2, BMP-6, IGF-1 and KL) and hormone receptors (FSH, LH and GH) in goat preantral follicles. To evaluate to stability of housekeeping genes micro dissected fresh follicles (150-200 MUm) as well as follicles that have been in vitro cultured for 12 days were used. In addition, isolated fresh follicles were used to compare expression of various growth factors and hormone receptors before culture. Both fresh and cultured follicles were subjected to total RNA extraction and synthesis of cDNA. After amplification of cDNA by real-time PCR, the geNorm software program was used to evaluate the stability of glyceraldehyde-2-phosphate dehydrogenase (GAPDH), beta-tubulin, beta-actin, phosphoglycerokinase (PGK), 18S rRNA, ubiquitin (UBQ) and ribosomal protein 19 (RPL-19). In addition, follicular steady-state levels of mRNA from the various growth factors under study were compared. Results demonstrated that, in goat preantral follicles, UBQ and beta actin were the most suitable reference genes and thus could be used as parameters to normalize data from future in vitro studies. In contrast, 18S RNA appeared the least stable gene among the tested housekeeping genes. Analysis of mRNA for several hypophyseal hormone receptors in fresh preantral follicles showed significantly higher FSH-R mRNA levels than those of LH-R and GH-R, and no difference between GH-R and LH-R mRNA levels. In regard growth factor mRNA expression in goat preantral follicles, EGF mRNA levels appeared significantly lower than those of the other studied growth factors. Increasingly higher relative mRNA levels were observed for GDF-9, BMP-15, BMP-6, FGF-2, VEGF, Kl and IGF-1, successively. In conclusion, UBQ and beta-actin are the most stable housekeeping genes in fresh and 12-days cultured caprine preantral follicles. Furthermore, in fresh follicles, high levels of FSH-R mRNA are detected while among eight growth factors, IGF-1 is the most highly expressed and EGF the weakest expressed compound. PMID- 20587135 TI - Detrimental effects of antibiotics on mouse embryos in chromatin integrity, apoptosis and expression of zygotically activated genes. AB - The effects of specific components in culture medium on embryo physiology have been extensively investigated to optimize in vitro culture systems; however, little attention has been paid to antibiotics, the reagents used most commonly in culture systems to prevent contamination. To investigate the potential effects of routine use of antibiotics on cultured embryos, mouse zygotes were cultured with or without antibiotics. In both groups, the developmental rate and cell number of blastocysts appear to be normal. The proportion of embryos with blastomere fragmentation increased slightly when embryos were cultured with antibiotics. In contrast, the presence of antibiotics in the embryo culture system significantly disturbs expression of zygotically activated genes, damages chromatin integrity and increases apoptosis of cultured embryos. These results provide evidence that, when cultured with antibiotics, embryos with normal appearance may possess intrinsic physiological and genetic abnormalities. We demonstrate that the adverse effects of antibiotics on mammalian embryos are more severe than we previously presumed and that antibiotics are not essential for sterility of embryo culture system therefore abolishing antibiotic supplementation during embryo culture. PMID- 20587136 TI - An efficient approach to isolation and characterization of pre- and postnatal umbilical cord lining stem cells for clinical applications. AB - There have been various forms of mesenchymal stem cell-like (MSC-like) cells isolated from umbilical cords (UCs). The isolation of umbilical cord lining stem cells (ULSCs) may be of great value for those interested in a possible treatment to several disease/disorders. Unlike umbilical cord blood cells, these cells are unique because they can be expanded to therapeutically relevant numbers and cryopreserved for several different uses. Here we efficiently isolate stem cells from a small segment of pre- and postnatal UCs, and obtain therapeutically relevant amounts of ULSCs within 3 weeks. We demonstrate their growth potential and characterize them using immunocytochemistry, flow cytometry, and RT-PCR. In addition, we differentiate ULSCs into multiple lineages. Pre- and postnatal ULSCs are morphologically similar to mesenchymal stem cells (MSCs) and easily expand to greater than 70 population doublings. They express pluripotent markers Oct4 and nanog at the protein and RNA level. Flow cytometry demonstrates that they express markers indicative of MSCs in addition to high SSEA-4 expression. ULSCs are easily differentiated into osteogenic, adipogenic, chondrogenic, cardiogenic, and neurogenic cells. Pre- and postnatal ULSCs are characteristically similar in respect to their growth, marker expression, and plasticity, demonstrating they are highly conserved throughout development. ULSCs have phenotypic and genotypic properties of MSCs. These studies demonstrate the therapeutic potential of an otherwise discarded tissue. They are a perfect HLA match for the donor and an excellent match for immediate family members; therefore, they may serve as a therapeutic cell source. PMID- 20587137 TI - Cardiac cell generation from encapsulated embryonic stem cells in static and scalable culture systems. AB - Heart diseases are major causes of morbidity and mortality linked to extensive loss of cardiac cells. Embryonic stem cells (ESCs) give rise to cardiomyocyte like cells, which may be used in heart cell replacement therapies. Most cardiogenic differentiation protocols involve the culture of ESCs as embryoid bodies (EBs). Stirred-suspension bioreactor cultures of ESC aggregates may be employed for scaling up the production of cardiomyocyte progeny but the wide range of EB sizes and the unknown effects of the hydrodynamic environment on differentiating EBs are some of the major challenges in tightly controlling the differentiation outcome. Here, we explored the cardiogenic potential of mouse ESCs (mESCs) and human ESCs (hESCs) encapsulated in poly-L-lysine (pLL)-coated alginate capsules. Liquefaction of the capsule core led to the formation of single ESC aggregates within each bead and their average size depended on the concentration of seeded ESCs. Encapsulated mESCs were directed along cardiomyogenic lineages in dishes under serum-free conditions with the addition of bone morphogenetic protein 4 (BMP4). Human ESCs in pLL-layered liquid core (LC) alginate beads were also differentiated towards heart cells in serum containing media. Besides the robust cell proliferation, higher fractions of cells expressing cardiac markers were detected in ESCs encapsulated in LC than in solid beads. Furthermore, we demonstrated for the first time that ESCs encapsulated in pLL-layered LC alginate beads can be coaxed towards heart cells in stirred-suspension bioreactors. Encapsulated ESCs yielded higher fractions of Nkx2.5- and GATA4-positive cells in the bioreactor compared to dish cultures. Differentiated cells formed beating foci that responded to chronotropic agents in an organotypic manner. Our findings warrant further development and implementation of microencapsulation technologies in conjunction with bioreactor cultivation to enable the production of stem cell-derived cardiac cells appropriate for clinical therapies and applications. PMID- 20587138 TI - Choice of immunosuppression influences cytomegalovirus DNAemia in cynomolgus monkey (Macaca fascicularis) islet allograft recipients. AB - This retrospective study reviews the results of our experience with the occurrence of CMV DNAemia in islet cell transplanted cynomolgus monkeys subjected to different immunosuppressive protocols, including induction treatment with thymoglobulin (TMG), with a combination of thymoglobulin and fludarabine (FLUD), with cyclophosphamide, or with daclizumab. CMV DNA in the peripheral blood (CMV DNAemia) of 47 monkeys was quantified by real-time PCR on a weekly to biweekly basis. As compared to other immunosuppressive regimens, and in association with greater decreases in WBC, lymphocyte, CD3+CD4+, and CD3+CD8+ lymphocyte counts, frequent CMV DNAemia occurred earlier (within the first month posttransplant), and was of greater severity and duration in recipients of TMG +/- FLUD. Treatment of recipients with alternative induction agents that resulted in less dramatic reductions in WBC and lymphocyte counts, however, resulted in occurrence of CMV DNAemia after postoperative day 60. The frequency, average intensity, duration, and area under the curve (AUC) for CMV DNAemia in animals receiving TMG +/- FLUD were 75-100%, 4.02 +/- 1.75 copies/ng DNA, 23.0 +/- 5.3 days, and 367.0 +/- 121.1 days * copies/ng DNA, respectively; corresponding values in animals receiving other treatments (0-44%, 0.19 +/- 0.10 copies/ng DNA, 0.5 +/- 0.3 days, and 75.4 +/- 40.2 days * copies/ng DNA, respectively) were significantly different. The value of WBC, T and B cells at the nadir of cell depletion greatly affects the occurrence of CMV DNAemia. No animals developed CMV DNAemia within the next 3 weeks when the lowest value of WBC, lymphocyte, CD3+, CD3+CD4+, CD3+CD8+, or CD20+ cells was above 4500, 1800, 300, 200, 150, or 300 cells/MUl, respectively. Oral valganciclovir prophylaxis did not completely prevent the appearance of CMV DNAemia. PMID- 20587139 TI - Transplantation of human Wharton's Jelly-derived stem cells alleviates chemically induced liver fibrosis in rats. AB - There is currently no effective treatment method available for liver fibrosis. We therefore evaluated the use of Wharton's jelly stem cells (WJSCs; the major umbilical cord stem cell population) to treat chemically induced liver fibrosis via intraperitoneal injection of thioacetamide. WJSCs were transplanted into liver-damaged rats via the portal vein and the treatment was evaluated by assessing serum biochemistry and histopathology. Transplanted WJSCs were distributed in the fibrotic area and around blood vessels, and hepatic recovery was accelerated. Serum prothrombin time significantly recovered, and serum albumin also improved at 21 days posttransplantation; collagen accumulation also decreased at 14 days. Thus, human WJSCs promoted recovery after chronic liver damage. Using immunohistochemical analyses, we determined that transplanted WJSCs produce albumin, hepatocyte growth factor (HGF), and metalloproteinase (MMP) after transplantation to chemically injured liver, indicating that WJSC may help to decrease liver collagen and thus may be useful for treating liver fibrosis. PMID- 20587141 TI - Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes. AB - For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, -C and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR) sequence-based typing and ABO genotyping was carried out by PCR restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6,740 donated cord bloods. When 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with <=2 mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO-compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population. PMID- 20587142 TI - Liposomal formulations of thrombomodulin increase engraftment after intraportal islet transplantation. AB - Early destruction of donor islet grafts due to an instant blood-mediated inflammatory reaction (IBMIR) remains a major obstacle in islet transplantation. Thrombomodulin plays an important role in limiting coagulation and inflammatory events through a variety of effects. In this study, we investigated the ability of thrombomodulin (TM), when reconstituted as a liposomal formulation, to enhance early syngeneic islet engraftment by minimizing or abrogating the IBMIR. Administration of TM significantly improved early engraftment of syngeneic islets after intraportal transplantation in diabetic mice. In the absence of treatment, conversion to euglycemia was observed among 46.6% (7/15) of recipients. In contrast, administration of TM led to euglycemia in 93.3% (14/15) of recipients (p = 0.0142). Recipients that received TM exhibited a lower incidence of primary nonfunction and better glucose control over a 30-day period after transplantation. Fibrin deposition (p < 0.05), neutrophil infiltration (p < 0.05), expression of TNF-alpha and IL-beta mRNA (p < 0.05), as well as NF-kappaB activity (p < 0.05) were significantly reduced in the liver of islet recipients having been treated with liposomal TM. These data demonstrate that TM significantly improves early syngeneic islet engraftment through effects that target both coagulation and inflammatory pathways. PMID- 20587143 TI - Beneficial effects of VEGF secreted from stromal cells in supporting endothelial cell functions: therapeutic implications for critical limb ischemia. AB - Critical limb ischemia (CLI) is the end stage of peripheral vascular disease (PVD). One third of CLI patients progresses to leg amputation with high associated morbidity and mortality. In no-option patients with end-stage critical limb ischemia, bone marrow cell transplantation has shown promising results, improving leg perfusion to the level of reducing major amputations and allowing limb salvage. We recently reported the successful application of an innovative protocol based on repeated autologous bone marrow cell transplantation, which resulted in an effective and feasible strategy for achieving long-term revascularization in patients with severe CLI. In an effort to understand the clinical benefit provided by stem cells therapy in patients with CLI, we characterized the marrow-derived stromal cells of CLI patients and we provided a correlation between the in vitro features of these cells and the clinical follow up at 12 months. We showed that cells derived from CLI patients had a reduced capacity to proliferate, adhere, and migrate, but that they stimulated proliferation and migration of endothelial cells through the release of VEGF-A, supporting the idea that the paracrine mechanisms underpinned the biological effects of long-term angiogenesis in CLI patients. PMID- 20587144 TI - Characteristics of CD133(+) human colon cancer SW620 cells. AB - Worldwide, colorectal cancer is the third most common type of cancer affecting both sexes. It has been proposed that a small subset of cancer cells (cancer stem cells) within each tumor is able to initiate tumor growth. In 2007, two research groups simultaneously identified a colon cancer stem cell population in human tumors by the use of CD133 expression. In the present study, we used a human colon cancer cell line, SW620, to analyze the cancer stem cell-like characteristics of CD133(+) cells in vitro and in vivo. In vitro, CD133(+) SW620 cells had a higher proliferative capacity, were more irradiation- and chemotherapy-resistant, and had a higher expression of beta-catenin compared with CD133(-) cells. Injections of either CD133(+) or CD133(-) cells into the skin or rectal mucosa of NOD/SCID mice led to tumors; however, injection of CD133(+) cells resulted in the formation of larger tumors. Tumors derived from injections of CD133(-) cells did not contain any CD133(+) cells, whereas tumors derived from injections of CD133(+) cells did contain CD133(+) cells, suggesting self-renewing capability. However, the proportion of CD133(+) cells in the newly formed tumors in vivo was lower than the proportion of CD133(+) cells in vitro. In conclusion, the human colon cancer cell line, SW620, contains both CD133(+) and CD133(-) phenotypes, and the CD133(+) phenotype has characteristics consistent with those of cancer stem cells. PMID- 20587146 TI - Characterization of human pancreatic progenitor cells. AB - beta-Cell replacement therapy via islet transplantation is an effective treatment for diabetes mellitus, but its widespread use is severely limited by the shortage of donor organs. Because pancreatic stem/progenitor cells are abundantly available in the pancreas of these patients and in donor organs, the cells could become a useful target for beta-cell replacement therapy. We previously established a mouse pancreatic stem cell line without genetic manipulation. In this study, we used the techniques to identify and isolate human pancreatic stem/progenitor cells. The cells from a duct-rich population were cultured in 23 kinds of culture media, based on media for mouse pancreatic stem cells or for human embryonic stem cells. The cells in serum-free media formed "cobblestone" morphologies, similar to a mouse pancreatic stem cell line. On the other hand, the cells in serum-containing medium and the medium for human embryonic stem cells formed "fibroblast-like" morphologies. The cells divided actively until day 30, and the population doubling level (PDL) was 6-10. However, the cells stopped dividing after 30 days in any culture conditions. During the cultures, the nucleus/cytoplasm (N/C) ratio decreased, suggesting that the cells entered senescence. Exendin-4 treatment and transduction of PDX-1 and NeuroD proteins by protein transduction technology into the cells induced insulin and pancreas related gene expression. Although the duplications of these cells were limited, this approach could provide a potential new source of insulin-producing cells for transplantation. PMID- 20587145 TI - Isolation and propagation of a human CD133(-) colon tumor-derived cell line with tumorigenic and angiogenic properties. AB - It has been proposed in human colorectal cancers (CRC) a minority subset of cancer cells within tumors able to initiate tumor growth, defined as cancer stem cells (CSC). Solid human primary colonic and its ovarian metastatic cancer tissues were collected from fresh surgical samples and subsequent xenografts were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The resulting tumors were disaggregated into single-cell suspensions and a CD133( ) cell line (NANK) was newly established and analyzed by flow cytometry. Surface markers of progenitor cells were immunophenotypically analyzed, and expression of stem cell and cancer-related genes was characterized. Secreted angiogenesis associated molecules were investigated by proteomic array technology. Finally, different numbers of NANK were implanted and their tumor-initiating properties were investigated in NOD/SCID mice. Intraperitoneal injection of NANK in NOD/SCID mice induced tumors with developing progressive peritoneal dissemination and ascites. NANK cells maintained a differentiated phenotype and reproduced the full morphologic and phenotypic heterogeneity of their parental lesions. Noticeably, NANK lacked the expression of conventional CSC markers CD133 and CD44, self renewal genes Oct-4 and Nanog, but showed the expression of an important gastrointestinal development marker CDX-2 and BMI-1 that is essential in regulating the proliferative activity of normal and leukemic stem cells. In addition, NANK secreted high amounts of important angiogenic cytokines. These results provide a novel and extensive model in human CSC for studying the generation and maintenance of phenotypic heterogeneity in CRC. PMID- 20587147 TI - Cell labeling with a novel contrast agent of magnetic resonance imaging. AB - Cell therapy is a proven and efficient method for treating multiple diseases. For both basic research and clinical practice, the development of noninvasive in vivo imaging methods is essential for monitoring the trafficking or homing of transplanted cells. One attractive approach for the effective imaging of transplanted cells is the efficient labeling of cells with a contrast agent. In this study, we developed a novel contrast agent of magnetic resonance imaging (MRI), TMADM-02. TMADM-02 was efficiently transduced into cells without toxicity. However, the aggregation of TMADM-02 was observed because of its low stability in culture medium. Therefore, TMADM-02 may have led to a false-positive test result. In future studies, we should verify not only the efficiency of labeling cells but also the stability of the contrast agent of MRI for clinical applications. PMID- 20587148 TI - Efficient transfection of sendai virus vector to mouse pancreatic stem cells in the floating state. AB - Sendai virus (SeV) vectors can efficiently introduce foreign genes without toxicity into various organs and are expected to be clinically applicable. We previously compared the transfectional efficiency of SeV and adenovirus (AdV) vectors by assessing the transfer of the green fluorescent protein (GFP) gene to pancreatic stem cells. Although the gene transfer efficiency was similar between these vectors, SeV vector had a lower toxicity in comparison to the AdV vector. In this study, we assessed the gene transfer efficiency of SeV vector in the floating state to pancreatic stem cells. The efficiency of gene transfer was much higher at all time points and at all concentrations in the floating state versus in the adhesion state. In addition, the pancreatic stem cells transfected with SeV in the floating state maintained their differentiation ability. These data suggest that SeV transfection to pancreatic stem cells in the floating state may be useful in gene transfer technology. PMID- 20587149 TI - Transduction of cell-penetrating peptides into induced pluripotent stem cells. AB - Induced pluripotent stem (iPS) cells have recently been generated by Yamanaka's group, and then followed by others. iPS cells are expected to have clinical applications including an important role in regenerative medicine. This study focused on the cell-penetrating peptides (CPPs) for differentiation or functional application of iPS cells, because several transduction domains can deliver a large size-independent variety of molecules into cells. Two CPPs, Texas Red-R8 and Rhodamine-TAT, were generated as representative CPPs and these CPPs were tested to determine their ability to penetrate the membrane of iPS cells. Both CPPs were transduced in iPS cells through macropinocytosis classified in endocytosis within 2 h in a manner consistent with many other cells, and no cytotoxicity and influence on their undifferentiated state was observed. In conclusion, CPPs can be utilized for their differentiation or functional application in iPS cells. PMID- 20587150 TI - N-acetylcysteine improves the viability of human hepatocytes isolated from severely steatotic donor liver tissue. AB - Hepatocyte transplantation is dependent on the availability of good quality human hepatocytes isolated from donor liver tissue. Hepatocytes obtained from livers rejected for transplantation on the grounds of steatosis are often of low viability and not suitable for clinical use. The aim of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the function of hepatocytes isolated from steatotic donor livers. Human hepatocytes were isolated from 10 severely steatotic (>60%) donor livers rejected for transplantation. The left lateral segment of the donor liver was dissected into two equal size pieces and randomized to NAC or control. NAC (5 mM) was added to the first perfusion buffer of the standard collagenase digestion technique. Cells from tissues perfused with NAC had a significantly higher mean viability (81.1 +/- 1.7% vs. 66.0 +/- 4.7%; p = 0.003) and cell attachment (1.08 +/- 0.26 vs. 0.67 +/- 0.18 OD units; p = 0.012). Addition of NAC during isolation of human hepatocytes from steatotic donor liver tissue significantly improved the outcome of cell isolation. Further studies are needed to investigate the mechanism(s) of this effect. Incorporation of NAC in the hepatocyte isolation protocol could increase the availability of hepatocytes for transplantation. PMID- 20587153 TI - Is it time to redefine "major operative procedures?". PMID- 20587151 TI - Autologous hematopoietic stem cell transplantation in 48 patients with end-stage chronic liver diseases. AB - The only presently viable treatment for end-stage liver disease is whole organ transplantation. However, there are insufficient livers available. The aim of the present study is to provide autologous bone marrow-derived stem cells as a potential therapeutic for patients with end-stage cirrhosis. This is a retrospective chart review of autologous stem cell treatment in 48 patients, 36 with chronic end-stage hepatitis C-induced liver disease and 12 with end-stage autoimmune liver disease. For all patients, granulocyte colony-stimulating factor was administered to mobilize their hematopoietic stem cells. Following leukapheresis, CD34(+) stem cells were isolated, amplified, and partially differentiated in culture, then reinjected into each subject via their hepatic artery or portal vein. Treatment was generally well tolerated with the expected moderate but transient bone pain from G-CSF in less than half of the patients. Three patients had serious treatment-related complications, and only 20.8% of these end-stage liver disease patients died during 12 months of follow up. For all patients there was a statistically significant decrease in ascites. There was clinical and biochemical improvement in a large percentage of patients who received the transplantation. In the viral group, there were marked changes in albumin (p = 0.0003), bilirubin (p = 0.04), INR (p = 0.0003), and ALT levels (p = 0.02). In the autoimmune group, values also improved significantly for albumin (p = 0.001), bilirubin (p = 0.002), INR (p = .0005), and ALT levels (p = 0.003). These results suggest that autologous CD34(+) stem cell transplantation may be safely administered and appears to offer some therapeutic benefit to patients with both viral and autoimmune-induced end-stage liver disease. PMID- 20587154 TI - Use of a body condition score technique to assess health status in a rat model of polycystic kidney disease. PMID- 20587155 TI - Transnational organizational considerations for sociocultural differences in ethics and virtual team functioning in laboratory animal science. AB - Business models for transnational organizations include linking different geographies through common codes of conduct, policies, and virtual teams. Global companies with laboratory animal science activities (whether outsourced or performed inhouse) often see the need for these business activities in relation to animal-based research and benefit from them. Global biomedical research organizations can learn how to better foster worldwide cooperation and teamwork by understanding and working with sociocultural differences in ethics and by knowing how to facilitate appropriate virtual team actions. Associated practices include implementing codes and policies transcend cultural, ethnic, or other boundaries and equipping virtual teams with the needed technology, support, and rewards to ensure timely and productive work that ultimately promotes good science and patient safety in drug development. PMID- 20587156 TI - Physiologic reference ranges for captive black-tailed prairie dogs (Cynomys ludovicianus). AB - The black-tailed prairie dog (Cynomys ludovicianus) is a member of the order Rodentia and the family Sciuridae. Ecologically, prairie dogs are a keystone species in prairie ecology. This species is used as an animal model for human gallbladder disease and diseases caused by infection with Clostridium difficile, Yersinia pestis, Francisella tularensis, and most recently, Orthopoxvirus. Despite increasing numbers of prairie dogs used in research and kept as pets, few data are available on their baseline physiology in animal facility housing conditions. To establish baseline physiologic reference ranges, we designed a study using 18 wild-caught black-tailed prairie dogs. Telemetry data were analyzed to establish circadian rhythms for activity and temperature. In addition, hematologic and serum chemistry analyses were performed. Baseline measurements were used to establish the mean for each animal, which then were compiled and analyzed to determine the reference ranges. Here we present physiologic data on serum chemistry and hematology profiles, as well as weight, core body temperature, and daily activity patterns for black-tailed prairie dogs. These results reflect the use of multiple measurements from species- and age matched prairie dogs and likely will be useful to ecologists, scientists interested in using this animal model in research, and veterinarians caring for pet prairie dogs. PMID- 20587157 TI - Identification of markers for imminent death in mice used in longevity and aging research. AB - The goal of this study was to identify objective criteria that would reliably predict imminent death in aged mice. Male and female ICR mice (age, 8 mo) were subcutaneously implanted with an identification chip for remote measurement of body temperature. Mice then were weighed and monitored regularly until spontaneous death occurred or until euthanasia was administered for humane reasons. Clinical signs that signaled implementation of euthanasia included inability to walk, lack of response to manipulation, large or ulcerated tumors, seizures, and palpable hypothermia. In mice that died spontaneously, gradual weight loss was the most frequent and earliest sign of imminent death. Hypothermia developed during the 2 wk prior to death. Slow or labored breathing were observed in about half of the mice before death. A composite score of temperature x weight can be used to provide an objective benchmark to signal increased observation or euthanasia of individual mice. Such assessment may allow the collection of terminal tissue samples without markedly altering longevity data, although application of this criterion may not be appropriate for all studies of longevity. Timely euthanasia of mice based on validated markers of imminent death can allow implementation of endpoints that alleviate terminal distress in aged mice, may not significantly affect longevity data, and can permit timely collection of biologic samples. PMID- 20587158 TI - Seasonal changes in the reproductive physiology of female rhesus macaques (Macaca mulatta). AB - Seasonal changes in menstrual cycle patterns and internal reproductive organs were studied in female rhesus macaques (n = 16) in indoor-outdoor housing in Chongqing, China. Uterine size and shape and endometrial thickening were evaluated during the early-secretory phase by using ultrasonography and MRI. From October to February, the macaques' menstrual cycles were short and regular, and the endometrial lining were easily visible by ultrasonography and MRI. However, from March through to September, menstrual cycles became irregular, endometrial lining were unclear, and the endometrium did not change markedly during the early secretory phase. We conclude that the reproductive season for a female rhesus macaque in Chongqing, China is from October through February, whereas the nonreproductive season is from March through September. The menstrual cycle patterns and reproductive organs of the macaques showed marked seasonal variation throughout the 12-mo observation period. In addition, uterine size, volume, and imaging characteristics varied dramatically between reproductive and nonreproductive seasons. PMID- 20587159 TI - Eradication of Helicobacter spp. by using medicated diet in mice deficient in functional natural killer cells and complement factor D. AB - A commercial 4-drug diet has shown promise in eradicating Helicobacter spp. from rodents; however, its effectiveness in immunocompromised mice is unknown. This study evaluated the efficacy of this treatment in eradicating Helicobacter spp. from mice deficient in functional natural killer cells (Cd1(-/-)) or complement factor D (Df(-/-)). Cd1(-/-) mice naturally infected with H. hepaticus with or without H. rodentium were fed either control or medicated diet for 8 wk followed by 4 wk on control diet. Fecal samples were PCR-evaluated for Helicobacter spp. before mice began treatment and then every 2 wk thereafter for 12 wk. The same experimental design was repeated for eighteen 9- to 21-wk-old Df(-/-) mice naturally infected with H. bilis with or without H. rodentium. All Df(-/-) mice and 8- to 21-wk-old Cd1(-/-) mice ceased shedding Helicobacter spp. after 2 wk of treatment and remained negative throughout the study. In contrast, the Cd1(-/-) mice that were 24 wk or older shed Helicobacter spp. for the first 8 wk but tested negative at 10 and 12 wk. All treated animals had enlarged ceca and gained less weight than control untreated mice, and 6 of 7 treated Cd1(-/-) male mice developed mild portal fibrosis. These findings show that within 2 wk of treatment, the 4-drug diet eradicated H. hepaticus and H. rodentium from young Cd1(-/-) mice and H. bilis and H. rodentium from Df(-/-) mice, but eradication of established infections in Cd1(-/-) mice required 8 wk of treatment. PMID- 20587160 TI - Vacuum-cleaner noise and acute stress responses in female C57BL/6 mice (Mus musculus). AB - Audiogenic stress is a well-documented phenomenon in laboratory rodents. Despite the recommendation in the Guide for the Care and Use of Laboratory Animals to consider noise a concern in the animal facility, only a small body of literature empirically addresses the effects of facility noise on laboratory rodents, particularly mice. The objective of this study was to determine whether facility noise generated by a vacuum cleaner induces an acute stress response in a commonly used strain of laboratory mouse under common housing conditions. In each of 2 experiments, 10 young adult, female C57BL/6Cr mice were exposed for 1 h to noise produced by a vacuum cleaner, and 10 control mice were not. In the first experiment, fecal samples were collected to measure concentrations of fecal corticosterone metabolites just before and 2, 4, 6, 8, 10, 14, 24, and 32 h after noise exposure. In the second experiment, stress-sensitive behavioral tests were performed 2 d before, immediately after, and 24 h after noise exposure. Physiologic and behavioral measurements indicated that vacuum cleaner noise did not cause an acute stress response in the noise-exposed mice but may have affected the diurnal variation of their corticosterone levels. These findings could contribute to the development of best practices in noise-control protocols for animal facilities. PMID- 20587161 TI - Development and implementation of multimedia content for an electronic learning course on rodent surgery. AB - The development of new rodent models of human disease and advances in surgical equipment and technologies have increased the demand for expertise in rodent surgery. Because of the limited availability of rodent surgical training courses, electronic (e-) learning is presented as an alternative to in-person education and as a means to hone the expertise of current surgeons in biomedical research, similar to e-learning applications for human surgery training. Translating this model to the biomedical research field provides participants with an opportunity to train themselves on rodent surgical techniques prior to operating on live models. An e-learning rodent surgery course was incorporated into a training class of undergraduate (n = 39) and graduate (n = 12) laboratory animal students, and a portion of the course was presented to laboratory animal professionals (n = 15). The effectiveness of the method was evaluated using written examination and postcourse surveys. The exam data demonstrated that the e-learning course transferred knowledge comparable to a lecture course on surgery that was presented in-person. Students responded favorably to videos, step-by-step photographs of surgical procedures, and the ready accessibility of the course. Critiques included the need to improve video resolution and quality of the voice overs. These results support the continued development and implementation of electronic rodent surgical technique courses for use in laboratory animal and biomedical research communities. PMID- 20587162 TI - Evaluation of a commercial colorimetric fecal dipstick assay for the detection of Helicobacter hepaticus infections in laboratory mice. AB - Mice used in biomedical research typically are tested for the presence of Helicobacter spp., including Helicobacter hepaticus. Here we evaluated the ability of a commercially available colorimetric Helicobacter dipstick assay to detect H. hepaticus in experimentally and naturally infected mice, with use of a Helicobacter PCR assay as the 'gold standard' test. None of the fecal samples from experimentally infected A/JCr mice (n = 12) tested positive for Helicobacter by the colorimetric dipstick test. In naturally infected A/JCr and C57BL/6 mice, 11% (1 of 9) and 30% (3 of 10) of fecal samples, respectively, tested positive for Helicobacter by the colorimetric dipstick assay. In these 3 groups of H. hepaticus-infected mice, statistically fewer mice tested positive by the colorimetric dipstick test than by PCR. The colorimetric Helicobacter dipstick assay had an overall diagnostic sensitivity of 13%, diagnostic specificity of 94%, and analytical sensitivity of 10(8) H. hepaticus cfu/mL. As currently formulated, the colorimetric dipstick assay had high specificity but lacked sensitivity for detecting H. hepaticus infections in 2 strains of mice commonly used in research, thereby limiting its utility as a diagnostic screening test for H. hepaticus infections in research mice. PMID- 20587163 TI - Euthanasia by CO2 inhalation affects potassium levels in mice. AB - We and others frequently have noted serum potassium levels of 8.0 +/- 0.85 mEq/L or greater in laboratory mice; this concentration has even been published as the upper limit of a 'normal' reference range. However, if bone fide, this potassium concentration would be incompatible with life in all species. We investigated conditions frequently encountered in the research setting to distinguish artifactual from true hyperkalemia. Variables evaluated included site of collection, time allowed for clot formation before serum separation, time elapsed between collection and analysis of samples collected in a serum separator tube, precollection method of anesthesia, and euthanasia technique. Serum potassium was measured from 75 C57BL/6NTac 10-wk-old female mice and divided into at least 5 mice per variable. Animals were euthanized by exsanguination immediately after terminal CO2 or ketamine-xylazine (KX) administration. Mice euthanized with CO2 had higher mean serum potassium (7.0 +/- 0.5 mEq/L) and range serum potassium (6.0 to 8.1 mEq/L) than did KX-treated mice. CO2 inhalation resulted in significantly lower blood pH (6.9 +/- 0.1), higher pCO2 (153.3 +/- 38.8 mm Hg), and higher lactate levels (3.9 +/- 0.9 mmol/L) than did KX anesthesia followed by exsanguination. These results suggest that antemortem respiratory acidosis from CO2 administration causes artifactual hyperkalemia in mice. Therefore, blood collection under KX anesthesia is preferable over CO2 inhalation to obtain accurate potassium values from mice. PMID- 20587164 TI - Evaluation of hydration and nutritional gels as supportive care after total-body irradiation in mice (Mus musculus). AB - Concern regarding the potential for radiation exposure from accidents or nuclear and radiologic terrorism is increasing. The purpose of this study was to determine whether the addition of minimal supportive care consisting of hydration or nutritional gels could be used to reduce mortality in mice exposed to (60)Co gamma-radiation. Male CD2F1 mice received 0, 8.50, or 9.25 Gy (60)Co at a dose rate of 0.6 Gy/min. These groups were further divided into 3 treatment groups that-in addition to pelleted food and water-received no supportive care, hydration gel, or nutritional gel. Overall survival, mean survival time, consumption of pelleted food and gel, and body weight were recorded for 30 d. Radiation caused dose-dependent decreases in overall survival, consumption of pelleted food and supplemental gel, and body weight. However, at each radiation dose (0, 8.50, 9.25 Gy), the type of supportive care did not modify overall survival, mean survival time, or changes in body weight. These results demonstrate that hydration and nutritional gels were not effective methods of supportive care after high-dose total body irradiation in mice. PMID- 20587165 TI - A spoonful of sugar helps the medicine go down: a novel technique to improve oral gavage in mice. AB - Oral gavage is a common route of precise oral dosing for studies in rodents. Complications including tracheal administration, esophageal trauma, and aspiration are common and usually related to animal resistance to the procedure, and the stress induced by oral gavage can be a confounding variable in many studies. The taste of sucrose conveys a pacifying and analgesic effect in newborns, whereas sour solutions can induce the swallow reflex in humans that are dysphagic. We hypothesized that precoating a gavage needle with sucrose or citrate (or both) would pacify mice and induce them to swallow, reducing the stress and complications associated with the technique. To validate this hypothesis, we quantitated time to passage, stress-related behavioral reactions to the procedure, and plasma corticosterone levels in mice after precoating gavage needles with water, sucrose, citrate, sucrose and citrate, or sodium chloride prior to oral gavage. Precoating needles with sucrose reduced the time to passage, decreased observable stress-related reactions to the procedure, and maintained plasma corticosterone levels similar to those in ungavaged control mice. Coating needles with water, sucrose and citrate, or citrate had no beneficial effects on these parameters. Our findings describe a novel, validated technique that measurably decreases signs of stress and thereby improves animal welfare during oral gavage. Furthermore, the use of sucrose may be a valuable tool to refine other minor or nonsurgical procedures in the field of laboratory animal research. PMID- 20587166 TI - Alternative method of oral dosing for rats. AB - Oral administration of drugs to laboratory rodents typically is achieved by using the gavage technique. Although highly effective, this method occasionally can cause esophageal injury as well as restraint-associated distress, particularly with repeated use. The aim of this study was to assess an alternative oral dosing method that could reduce the distress and morbidity associated with standard gavage techniques. The palatability and pharmacokinetic profile of 2 medicines approved for the treatment of Alzheimer disease, donepezil and galantamine, were investigated in male Lister hooded rats by using a syringe-feeding method and compared with results from traditional gavage administration. In addition, the stimulant nicotine was tested by using the syringe-feeding method in a separate series of experiments. Animals reliably learned to drink voluntarily from the syringe, and latency to drink decreased rapidly. The addition of donepezil, galantamine, or nicotine to sucrose had no apparent effect on the palatability of the solution, although nicotine produced aversive effects that inhibited subsequent voluntary intake. Oral bioavailability was improved by using syringe feeding with donepezil but not galantamine. Both drugs improved cognitive performance in the novel object recognition test, with similar behavioral profiles between the 2 methods of administration. Our results suggest that the syringe-feeding technique is an effective alternative oral dosing method in rats. PMID- 20587168 TI - Effect of body position on limb lead electrocardiographic findings in sedated cynomolgus macaques (Macaca fascicularis). AB - Electrocardiograms (ECGs) often are collected from sedated cynomolgus macaques (Macaca fascicularis) in drug safety studies to support investigational new drug applications. ECGs are evaluated either manually or electronically, and the quality of the ECG tracing can affect the quality of that evaluation. The body position of the subject sometimes is manipulated to eliminate noise or clarify ECG complex morphology, and typically multiple technicians collect ECG data over time. Both factors-body position and multiple technicians-could affect ECG quality. This study was designed to determine whether body position or multiple technicians affects heart rate, mean electrical axis, or ECG parameters (RR interval, P wave duration, PR interval, QRS duration, QT interval (uncorrected and rate-corrected by using the Bazett [QTcb] and Fridericia [QTcf] formulas), P wave amplitude, R wave amplitude, T wave height, T wave height negative, and ST segment elevation). The results reveal minimal (coefficient of variation [CV] less than 10%) within-animal variation between body positions (ventral, dorsal, right or left lateral), with the exception of P wave amplitude (17.5%), R wave amplitude (23.7%), and ST segment elevation (43%). Minimal variation in ECG parameters (no more than 7%) was detected between technicians, across animals, and across body positions. These findings suggest that neither a change in body position to increase the quality of an ECG tracing nor the use of multiple technicians significantly affect the evaluation of quantitative ECG parameters, especially QTcb (0.1% CV) and QTcf (1.3% CV). PMID- 20587167 TI - Effective and safe anesthesia for Yorkshire and Yucatan swine with and without cardiovascular injury and intervention. AB - The goal of this study was to identify an injectable anesthetic protocol that provides sedation sufficient for peripheral vascular catheterization, intubation, and transport while minimizing cardiovascular changes in Yorkshire and Yucatan pigs with and without cardiovascular injury and intervention (CI). Phase 1 examined the safety and efficacy of acepromazine-ketamine, diazepam-ketamine, midazolam-ketamine, and medetomidine-ketamine in 5 healthy Yorkshire pigs. For each drug combination, we obtained multiple measurements of heart rate, blood pressure, respiratory rate, temperature, sedation score, ability to catheterize and intubate, and recovery score. Phase 2 evaluated and refined the dose of the most effective Phase 1 anesthetic combination (midazolam-ketamine) in healthy and CI Yorkshire pigs (n = 53 trials). Phase 3 mirrored Phase 2 but tested midazolam ketamine in healthy and CI Yucatan pigs (n = 34 trials). Midazolam (0.5 mg/kg) ketamine (25 to 27 mg/kg) was the most effective anesthetic combination in healthy Yorkshire pigs, but this dose was less effective in healthy Yucatan pigs and CI Yorkshire and Yucatan pigs. Midazolam-ketamine resulted in tachycardia and apnea more frequently in CI pigs than healthy pigs. This combination also caused vomiting in one CI Yucatan pig. Overall, midazolam-ketamine provided safe and effective sedation for catheterization and intubation of both healthy and CI pigs. This study suggests Yucatan pigs may require a higher dose midazolam ketamine to achieve the same level of sedation as that in Yorkshire pigs. Although anesthetic complication rates were higher in CI pigs, our results indicate that midazolam-ketamine can be safely used for sedation of both pig breeds with and without CI. PMID- 20587169 TI - Cleft lip and palate associated with other malformations in a neotropical primate (Saimiri ustus). AB - Cleft lip (with or without cleft palate) has been documented in several species of nonhuman primates, which in general are susceptible at similar doses and stages of gestation to the same teratogens as humans. Cleft lip can be unilateral or bilateral, isolated, syndromic, familial, or genetic. Here we report the first case of syndromic cleft lip and palate in a male bare-eared squirrel monkey (Saimiri ustus). Associated with the orofacial clefts, the monkey manifested absence of bones, malformation of vertebrae L3, only 4 fingers in each hand, and shortening of tendons leading to inflection of the hands and fingers. Previous reports describing cleft lip and palate in other squirrel monkeys (Saimiri sciureus) in other breeding units have suggested consanguineous mating as a possible cause. Although the etiology in the case we present is unknown, we discuss factors associated with orofacial clefts in humans and various nonhuman primates. PMID- 20587170 TI - Intraoperative intracerebral MRI-guided navigation for accurate targeting in nonhuman primates. AB - During in vivo intracerebral infusions, the ability to perform accurate targeting towards a 3D-specific point allows control of the anatomical variable and identification of the effects of variations in other factors. Intraoperative MRI navigation systems are currently being used in the clinic, yet their use in nonhuman primates and MRI monitoring of intracerebral infusions has not been reported. In this study rhesus monkeys were placed in a MRI-compatible stereotaxic frame. T1 MRIs in the three planes were obtained in a 3.0T GE scanner to identify the target and plan the trajectory to ventral postcommisural putamen. A craniotomy was performed under sterile surgical conditions at the trajectory entry point. A modified MRI-compatible trajectory guide base (Medtronic Inc.) was secured above the cranial opening and the alignment stem applied. Scans were taken to define the position of the alignment stem. When the projection of the catheter in the three planes matched the desired trajectory to the target, the base was locked in position. A catheter replaced the alignment stem and was slowly introduced to the final target structure. Additional scans were performed to confirm trajectory and during the infusion of a solution of gadoteridol (ProHance, Bracco Diagnostics; 2 mM/L) and bromophenol blue (0.16 mg/ml) in saline. Monitoring of the pressure in the infusion lines was performed using pressure monitoring and infusion pump controller system (Engineering Resources Group Inc.) in combination with a MRI-compatible infusion pump (Harvard). MRI during infusion confirmed successful targeting and matched postmortem visualization of bromophenol blue. Assessment of the accuracy of the targeting revealed an overall 3D mean +/- SD distance error of 1.2 +/- 0.6 mm and angular distance error of 0.9 +/- 0.5 mm. Our results in nonhuman primates confirm the accuracy of intraoperative MRI intracerebral navigation combined with an adaptable, pivot point-based targeting system and validates its use for preclinical intracerebral procedures. PMID- 20587171 TI - Hand surgery after axillary lymph node clearance for breast cancer: contra indication to surgery? AB - INTRODUCTION: Breast cancer patients who have had prior axillary lymph node clearance (ALNC) can present with ipsilateral hand conditions that could easily be treated with surgical intervention. These patients are often advised to avoid interventional procedures due to risks of complications such as lymphoedema, infection and cellulitis. SUBJECTS AND METHODS: Between April and June 2009, we conducted an online survey of hand surgeons, breast surgeons and breast-care nurses to obtain their views on hand surgery after ipsilateral axillary lymph node clearance. RESULTS: The majority of hand surgeons (58%) felt there was no contra-indication to surgery in a breast cancer patient with prior ipsilateral ALNC compared to just 30% of breast surgeons and 10% of breast-care nurses. The majority of breast surgeons and breast-care nurses (70% and 89%, respectively) felt that hand surgery was a relative contra-indication compared to just 41% of hand surgeons. Postoperative lymphoedema was the commonest cited reason for avoiding surgery. The majority of hand surgeons (79%) and nearly two-thirds of breast surgeons (57%) would use a tourniquet during surgery if it was normal practice. CONCLUSIONS: A review of the published literature does not support the notion that these patients experience increased complications; therefore, we recommend the advice given to breast cancer patients regarding ipsilateral surgery be re-evaluated. PMID- 20587173 TI - 15th International Workshop on Campylobacter, Helicobacter and Related Organisms. AB - The purpose of this communication is to update the veterinary public health community as to what poultry-related interventions were presented at the recent biennial International Workshop on Campylobacter, Helicobacter and Related Organisms (CHRO), which was held in Niigata, Japan, September 2-5, 2009. More than 30 years have passed since the publication of Martin Skirrow's seminal paper in the British Medical Journal in which he described Campylobacter enteritis as a new disease (1). This publication precipitated a global interest in thermophilic campylobacters. Three decades later, these organisms still pose a grave threat to public health. Furthermore, 10 years have passed since Parkhill et al. published the genome sequence of Campylobacter jejuni NCTC11168 (2). PMID- 20587174 TI - Persistence of highly pathogenic avian influenza viruses in natural ecosystems. AB - Understanding of ecologic factors favoring emergence and maintenance of highly pathogenic avian influenza (HPAI) viruses is limited. Although low pathogenic avian influenza viruses persist and evolve in wild populations, HPAI viruses evolve in domestic birds and cause economically serious epizootics that only occasionally infect wild populations. We propose that evolutionary ecology considerations can explain this apparent paradox. Host structure and transmission possibilities differ considerably between wild and domestic birds and are likely to be major determinants of virulence. Because viral fitness is highly dependent on host survival and dispersal in nature, virulent forms are unlikely to persist in wild populations if they kill hosts quickly or affect predation risk or migratory performance. Interhost transmission in water has evolved in low pathogenic influenza viruses in wild waterfowl populations. However, oropharyngeal shedding and transmission by aerosols appear more efficient for HPAI viruses among domestic birds. PMID- 20587175 TI - Extensive drug resistance in malaria and tuberculosis. AB - Drug resistance in malaria and in tuberculosis (TB) are major global health problems. Although the terms multidrug-resistant TB and extensively drug resistant TB are precisely defined, the term multidrug resistance is often loosely used when discussing malaria. Recent declines in the clinical effectiveness of antimalarial drugs, including artemisinin-based combination therapy, have prompted the need to revise the definitions of and/or to recategorize antimalarial drug resistance to include extensively drug-resistant malaria. Applying precise case definitions to different levels of drug resistance in malaria and TB is useful for individual patient care and for public health. PMID- 20587176 TI - Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. AB - We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised. PMID- 20587177 TI - Population structure of East African relapsing fever Borrelia spp. AB - Differentiation of endemic East African tick-borne relapsing fever Borrelia duttonii spirochetes from epidemic louse-borne relapsing fever (LBRF) B. recurrentis spirochetes into different species has been questioned. We assessed a noncoding intragenic spacer (IGS) region to compare genotypes found in clinical samples from relapsing fever patients. Although IGS typing was highly discriminatory and resolved 4 East African tick-borne relapsing fever groups from a disease-endemic region in Tanzania, 2 IGS clades were found among LBRF patients in Ethiopia. The 2 IGS sequence types for B. recurrentis overlapped with 2 of the 4 groups found among B. duttonii. All cultivable isolates of B. duttonii fell into a single IGS cluster, which suggests their analysis might introduce selective bias. We provide further support that B. recurrentis is a subset of B. duttonii and represents an ecotype rather than a species. These observations have disease control implications and suggest LBRF Borrelia spp. could reemerge from its tick-borne reservoirs where vectors coexist. PMID- 20587178 TI - Human Infection with Rickettsia felis, Kenya. AB - To determine the cause of acute febrile illnesses other than malaria in the North Eastern Province, Kenya, we investigated rickettsial infection among patients from Garissa Provincial Hospital for 23 months during 2006-2008. Nucleic acid preparations of serum from 6 (3.7%) of 163 patients were positive for rickettsial DNA as determined by a genus-specific quantitative real-time PCR and were subsequently confirmed by molecular sequencing to be positive for Rickettsia felis. The 6 febrile patients' symptoms included headache; nausea; and muscle, back, and joint pain. None of the patients had a skin rash. PMID- 20587179 TI - Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007-2008. AB - During August 2007-February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78-8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions. PMID- 20587180 TI - High diversity and ancient common ancestry of lymphocytic choriomeningitis virus. AB - Lymphocytic choriomeningitis virus (LCMV) is the prototype of the family Arenaviridae. LCMV can be associated with severe disease in humans, and its global distribution reflects the broad dispersion of the primary rodent reservoir, the house mouse (Mus musculus). Recent interest in the natural history of the virus has been stimulated by increasing recognition of LCMV infections during pregnancy, and in clusters of LCMV-associated fatal illness among tissue transplant recipients. Despite its public health importance, little is known regarding the genetic diversity or distribution of virus variants. Genomic analysis of 29 LCMV strains collected from a variety of geographic and temporal sources showed these viruses to be highly diverse. Several distinct lineages exist, but there is little correlation with time or place of isolation. Bayesian analysis estimates the most recent common ancestor to be 1,000-5,000 years old, and this long history is consistent with complex phylogeographic relationships of the extant virus isolates. PMID- 20587181 TI - Zoonotic transmission of avian influenza virus (H5N1), Egypt, 2006-2009. AB - During March 2006-March 2009, a total of 6,355 suspected cases of avian influenza (H5N1) were reported to the Ministry of Health in Egypt. Sixty-three (1%) patients had confirmed infections; 24 (38%) died. Risk factors for death included female sex, age > or = 15 years, and receiving the first dose of oseltamivir >2 days after illness onset. All but 2 case-patients reported exposure to domestic poultry probably infected with avian influenza virus (H5N1). No cases of human-to human transmission were found. Greatest risks for infection and death were reported among women > or = 15 years of age, who accounted for 38% of infections and 83% of deaths. The lower case-fatality rate in Egypt could be caused by a less virulent virus clade. However, the lower mortality rate seems to be caused by the large number of infected children who were identified early, received prompt treatment, and had less severe clinical disease. PMID- 20587182 TI - Deforestation and malaria in Mancio Lima County, Brazil. AB - Malaria is the most prevalent vector-borne disease in the Amazon. We used malaria reports for health districts collected in 2006 by the Programa Nacional de Controle da Malaria to determine whether deforestation is associated with malaria incidence in the county (municipio) of Mancio Lima, Acre State, Brazil. Cumulative percent deforestation was calculated for the spatial catchment area of each health district by using 60 x 60-meter, resolution-classified imagery. Statistical associations were identified with univariate and multivariate general additive negative binomial models adjusted for spatial effects. Our cross sectional study shows malaria incidence across health districts in 2006 is positively associated with greater changes in percentage of cumulative deforestation within respective health districts. After adjusting for access to care, health district size, and spatial trends, we show that a 4.2%, or 1 SD, change in deforestation from August 1997 through August 2001 is associated with a 48% increase of malaria incidence. PMID- 20587183 TI - Fatal babesiosis in man, Finland, 2004. AB - We report an unusual case of human babesiosis in Finland in a 53-year-old man with no history of splenectomy. He had a rudimentary spleen, coexisting Lyme borreliosis, exceptional dark streaks on his extremities, and subsequent disseminated aspergillosis. He was infected with Babesia divergens, which usually causes bovine babesiosis in Finland. PMID- 20587184 TI - Postexposure treatment of Marburg virus infection. AB - Rhesus monkeys are protected from disease when a recombinant vesicular stomatitis virus-based vaccine is administered 20-30 min after infection with Marburg virus. We protected 5/6 monkeys when this vaccine was given 24 h after challenge; 2/6 animals were protected when the vaccine was administered 48 h postinfection. PMID- 20587185 TI - Detection of Lassa virus, Mali. AB - To determine whether Lassa virus was circulating in southern Mali, we tested samples from small mammals from 3 villages, including Soromba, where in 2009 a British citizen probably contracted a lethal Lassa virus infection. We report the isolation and genetic characterization of Lassa virus from an area previously unknown for Lassa fever. PMID- 20587186 TI - Septicemia caused by tick-borne bacterial pathogen Candidatus Neoehrlichia mikurensis. AB - We have repeatedly detected Candidatus Neoehrlichia mikurensis, a bacterium first described in Rattus norvegicus rats and Ixodes ovatus ticks in Japan in 2004 in the blood of a 61-year-old man with signs of septicemia by 16S rRNA and groEL gene PCR. After 6 weeks of therapy with doxycycline and rifampin, the patient recovered. PMID- 20587187 TI - Evolution of seventh cholera pandemic and origin of 1991 epidemic, Latin America. AB - Thirty single-nucleotide polymorphisms were used to track the spread of the seventh pandemic caused by Vibrio cholerae. Isolates from the 1991 epidemic in Latin America shared a profile with 1970s isolates from Africa, suggesting a possible origin in Africa. Data also showed that the observed genotypes spread easily and widely. PMID- 20587188 TI - Vaccine-associated paralytic poliomyelitis in immunodeficient children, Iran, 1995-2008. AB - To determine the prevalence of vaccine-associated paralytic poliomyelitis (VAPP) in immunodeficient infants, we reviewed all documented cases caused by immunodeficiency-associated vaccine-derived polioviruses in Iran from 1995 through 2008. Changing to an inactivated polio vaccine vaccination schedule and introduction of screening of neonates for immunodeficiencies could reduce the risk for VAPP infection. PMID- 20587189 TI - Dogs as sentinels for human infection with Japanese encephalitis virus. AB - Because serosurveys of Japanese encephalitis virus (JEV) among wild animals and pigs may not accurately reflect risk for humans in urban/residential areas, we examined seroprevalence among dogs and cats. We found that JEV-infected mosquitoes have spread throughout Japan and that dogs, but not cats, might be good sentinels for monitoring JEV infection in urban/residential areas. PMID- 20587190 TI - Rickettsia felis-associated uneruptive fever, Senegal. AB - During November 2008-July 2009, we investigated the origin of unknown fever in Senegalese patients with a negative malaria test result, focusing on potential rickettsial infection. Using molecular tools, we found evidence for Rickettsia felis-associated illness in the initial days of infection in febrile Senegalese patients without malaria. PMID- 20587191 TI - Novel human parvovirus 4 genotype 3 in infants, Ghana. AB - Human parvovirus 4 has been considered to be transmitted only parenterally. However, after novel genotype 3 of parvovirus 4 was found in 2 patients with no parenteral risks, we tested infants in Ghana. A viremia rate of 8.6% over 2 years indicates that this infection is common in children in Africa. PMID- 20587192 TI - Geographic differences in genetic locus linkages for Borrelia burgdorferi. AB - Borrelia burdorferi genotype in the northeastern United States is associated with Lyme borreliosis severity. Analysis of DNA sequences of the outer surface protein C gene and rrs-rrlA intergenic spacer from extracts of Ixodes spp. ticks in 3 US regions showed linkage disequilibrium between the 2 loci within a region but not consistently between regions. PMID- 20587193 TI - Accumulation of L-type bovine prions in peripheral nerve tissues. AB - We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues. PMID- 20587194 TI - Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. AB - We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America. PMID- 20587195 TI - Saffold cardioviruses of 3 lineages in children with respiratory tract infections, Beijing, China. AB - To clarify the potential for respiratory transmission of Saffold cardiovirus (SAFV) and characterize the pathogen, we analyzed respiratory specimens from 1,558 pediatric patients in Beijing. We detected SAFV in 7 (0.5%) patients and identified lineages 1-3. However, because 3 patients had co-infections, we could not definitively say SAFV caused disease. PMID- 20587196 TI - Novel swine influenza virus reassortants in pigs, China. AB - During swine influenza virus surveillance in pigs in China during 2006-2009, we isolated subtypes H1N1, H1N2, and H3N2 and found novel reassortment between contemporary swine and avian panzootic viruses. These reassortment events raise concern about generation of novel viruses in pigs, which could have pandemic potential. PMID- 20587197 TI - Long-term shedding of influenza A virus in stool of immunocompromised child. AB - In immunocompromised patients, influenza infection may progress to prolonged viral shedding from the respiratory tract despite antiviral therapy. We describe chronic influenza A virus infection in an immunocompromised child who had prolonged shedding of culturable influenza virus in stool. PMID- 20587198 TI - Human parechovirus infections in monkeys with diarrhea, China. AB - Information about human parechovirus (HPeV) infection in animals is scant. Using 5' untranslated region reverse transcription-PCR, we detected HPeV in feces of monkeys with diarrhea and sequenced the complete genome of 1 isolate (SH6). Monkeys may serve as reservoirs for zoonotic HPeV transmissions and as models for studies of HPeV pathogenesis. PMID- 20587199 TI - ACC-1 beta-Lactamase-producing Salmonella enterica Serovar Typhi, India. PMID- 20587200 TI - Endocarditis caused by Actinobaculum schaalii, Austria. PMID- 20587201 TI - Mycobacterium chelonae wound infection after liposuction. PMID- 20587202 TI - Influenza A pandemic (H1N1) 2009 virus and HIV. PMID- 20587203 TI - Roseomonas sp. isolated from ticks, China. PMID- 20587204 TI - Misindentification of Mycobacterium kumamotonense as M. tuberculosis. PMID- 20587205 TI - Mycobacterium conceptionense infection after breast implant surgery, France. PMID- 20587206 TI - Rapid diagnostic tests and severity of illness in pandemic (H1N1) 2009, Taiwan. PMID- 20587207 TI - Human Brucella canis infections diagnosed by blood culture. PMID- 20587208 TI - Oseltamivir-resistant pandemic (H1N1) 2009 in patient with impaired immune system. PMID- 20587209 TI - Sapovirus in adults in rehabilitation center, upper Austria. PMID- 20587210 TI - There is always something new out of Africa. AB - Lone survivor of seven sets of twins born to his mother, he started life as a legend among the Yoruba in Nigeria, who have one of the highest rates of twin births and infant deaths in the world. According to family lore, he was the spirit that kept trying to be born and kept being turned back, the child "born to die." Bamidele to his father, Olaniyi to his grandmother, Prince Twins Seven Seven renamed himself in adulthood to commemorate newly found royal lineage and the circumstances of his birth, which colored his life and shaped his art. Deeply conscious of these aspects of his nature, he has conveyed in art his personal understanding of a world teeming with spirits and populated with myths. PMID- 20587211 TI - Endovascular Pressure Measurements: Validation with a Pulsatile Flow Model and Haemodynamic Assessment of Brain AVMs. AB - SUMMARY: Intravascular pressure measurements for several types of endovascular catheters were obtained in an in vitro model to validate the pressure readings obtained during the interventional procedures of brain AVM embolization. An experimental model was used where the beat rate, flow and pressures were as close as possible to the average human values of interest. It is shown that the corrections increase with the decreasing inner diameter of the catheter used and with increasing vascular pressure. We have also shown that there were no differences between measurements made with the catheter in the direction of flow or against it. An average pressure reading corrections for the various microcatheters to compensate the readings obtained during in vivo monitoring is presented. The haemodynamic assessment of 81 brain AVMs was performed using the endovascular measurement of arterial pressure in 389 feeding arteries during embolization. Mostly, the feeders' arterial median pressure was half the systemic arterial pressure but there was a wide variability of AV shunts in brain AVMs not only from one brain AVM to another but also within the same brain AVM. Measurement of arterial feeder pressure is an inexpensive, quick and accurate tool to evaluate the type of AV shunts within brain AVM. PMID- 20587212 TI - The so-called anterior meningeal artery: an anatomic study for treatment modalities. AB - SUMMARY: The so called anterior meningeal artery (AMA) is a branch of the vertebral artery (VA), which had been interpreted as a supplying vessel of the dura in the foramen magnum and upper cervical level. In this study, we examined the anatomy of this artery and relationships to its surrounding structures for treatment modalities. With the aid of magnification, five adult cadaveric head and neck complex and five cervical spines were examined after perfusion of the vessels with colored silicone. The AMA arose from the VA between the C2 and C3 level, and passed medially through the intrervertebral foramen anterior to the dural sheath of the third cervical nerve root. It ran upwards dorsal to the deep layer of the posterior longitudinal ligament (PLL) with anterior internal vertebral venous plexus. Rostrally, it formed an arcade above the apex of the odontoid process with its contralateral mate. The AMA gave off several tiny branches to the deep layer of the PLL, ligaments and soft tissues above the apex of the odontoid process, and vertebral bodies of the axis. At the level of the foramen magnum, it ended in several small twigs to the dura. Anastomoses between the AMA system and adjacent vessels were observed. One was directed through the hypoglossal canal to the ascending pharyngeal artery and the other was with the V3 segment of the VA. The origin and course of the two AMA, and anastomoses were symmetric. Although the AMA feeds the ventral dura of the foramen magnum, the perfusion area is larger than its name suggests, including the bony and ligamentous structures in the craniovertebral junction. Anatomical knowledge of the AMA, including its anastomoses and layer relationships to the surrounding structures, may help to perform treatment modalities in this region rationally. PMID- 20587213 TI - "Duplicated" or "multiple" cervical internal carotid and vertebral arteries from fenestration, duplication and vasa vasorum to segmental rete. AB - SUMMARY: The appearance of multiple cervical arteries may be due to a variety of anatomic situations. Arterial fenestrations and duplications have different anatomic origins, with distinct appearances on angiography. They are associated with incomplete segmental development. The vasa vasorum of the internal carotid artery are rarely seen unless enlarged in pathological situations. They represent a peculiar segmental, in-situ, collateral circulation. Retes, on the other hand, correspond to a more complex reconstitution of an early segmental regression. Careful analysis of each of these features is required to choose the best appropriate terminology. The purpose of this paper is to report illustrative cases to enhance the distinctive features of each disposition. PMID- 20587214 TI - A five-vessel aortic arch with an anomalous origin of both vertebral arteries and an aberrant right subclavian artery. AB - SUMMARY: In this case presentation we describe a patient with an anomalous origin of the right vertebral artery arising from the right common carotid artery in combination with an aberrant right subclavian artery and a left vertebral artery originating from the arch between the left common carotid artery and left subclavian artery. Hence there were five vessels originating from the aortic arch. The possible embryological mechanism as well as a postulation on the importance of the level of entrance of the vertebral artery in the cervical transverse foramen is discussed. PMID- 20587215 TI - Endovascular treatment of basilar artery dissection by stent deployment. A case report. AB - SUMMARY: We describe a 44 year-old woman with dissection of the distal third of the basilar artery presenting with subarachnoid haemorrhage. She was treated with a Neuroform stent (Boston Scientific), the first stent designed for intracranial navigation and recently approved by the FDA to treat wide-necked cerebral aneurysms and allow reconstruction of the internal lumen. In our patient, the dissection involved the origin of the anterosuperior cerebellar artery and the origin of the right posterior cerebral artery. The stent was positioned without complications during or after the procedure. Intra and periprocedural thrombolytic therapy was given followed by an antiaggregant (100 mg Aspirin) for a year after treatment. Subsequent angio-MR and angiographic monitoring disclosed resolution of the dissection and normalization of the basilar artery lumen. She currently lives a controlled but normal life. PMID- 20587216 TI - Oral contraceptive induced cerebral venous thrombosis treated by local catheter directed thrombolysis. AB - SUMMARY: We report on a case of cerebral venous thrombosis (CVT) induced by oral contraception (OC) activated coagulopathy and its endovascular treatment. Deep venous system and dural sinuses thrombosis complicated with severe neurological deficit and coma due to right thalamic edema and ischemia in a young woman was treated by local thrombolysis with an administration of 0.6 mg/h of the rtPA and the concomitant intravenous unfractioned heparin infusion (700 IU/h). 3D-Xra digital rotational venography performed at the beginning and after treatment confirmed thrombus resolution with rapid flow restoration. Dynamic flow imaging gives interesting information on the deep venous system and the cortical venous collectors drainage. Final NIHSS (National Institute of Health Stroke Scale) and mRS (modified Rankin Scale) confirmed an excellent clinical outcome of the interventional therapy. PMID- 20587217 TI - Spinal Brucellosis with Paraspinal Abscess Formation Treated with CT Guided Percutaneous Abscess Drainage. AB - SUMMARY: Although brucellosis may be present in various systems, osteoarticular brucellosis is a serious complication of human brucellosis. We present two cases of Brucellar spondylitis (BS) having paraspinal abscess with epidural extension. The first case of non-complicated paraspinal abscess was treated effectively with percutaneous abscess drainage and antibrucellar chemotherapy. However, the second case with disseminated BS and multiseptated large abscess did not respond to needle drainage with medical treatment. Because of the persistence and re-growth of the abscess, he was treated with percutaneous catheter drainage using the Seldinger technique. They showed adequate radiological and clinical response to drainage and antibrucellar chemotherapy. PMID- 20587218 TI - Multiple cerebral aneurysms in a patient with recurrent cardiac myxomas. A case report. AB - SUMMARY: A 22 year old female presented in 1987 a cardiac myxoma, removed in 1991. In 1992 catheter angiography showed bilateral aneurysms. Conservative treatment was elected. In 2000 recurrence of the myxoma and subsequent removal, prompted new angiography. All aneurysms had decreased in size, some had spontaneously disappeared. PMID- 20587219 TI - Dissecting aneurysm of the anterior cerebral artery presenting with thrombo embolic complications. A case report. AB - SUMMARY: A dissecting aneurysm of the anterior cerebral artery is a relatively rare disorder. A patient is presented with mild symptoms due to thromboembolic complications from a dissecting aneurysm of the pericallosal artery. The patient had a good outcome after conservative treatment. A review of the literature is presented. PMID- 20587220 TI - Intracranial dural arteriovenous fistula presenting with tetraparesis due to cervicomedullary junction compression. A case report. AB - SUMMARY: Cranial dural arteriovenous fistulas (DAVFs) may give rise to myelopathy due to spinal perimedullary venous drainage causing intramedullary venous hypertension. Such cases are uncommon but not rare, with several cases reported in the literature. We report a case of foramen magnum DAVF presenting with symptoms of tetraparesis. The unusual feature was that in this case it was due to compression of the cervicomedullary junction by a large venous pouch rather than the result of spinal perimedullary venous hypertension. Transarterial glue embolization achieved good reduction of flow in the fistula with shrinkage of the venous pouch and corresponding clinical improvement. PMID- 20587221 TI - New Devices Designed to Improve the Long-Term Results of Endovascular Treatment of Intracranial Aneurysms. A Proposition for a Randomized Clinical Trial to Assess their Safety and Efficacy. AB - SUMMARY: Endovascular coiling can improve the outcome of patients with ruptured intracranial aneurysms, but angiographic recurrences are frequent compared to surgical clipping. New coils or devices have been introduced to improve long-term results of endovascular treatment but none have been the object of a valid clinical trial. We have proposed a multicentric randomized double-blind study comparing radioactive and standard coil occlusion of aneurysms. The purpose of this article is to review issues that are specific to the design of clinical trials to assess embolic agents that could improve the long-term efficacy of endovascular treatment of intracranial aneurysms. The proposed trial is a randomized, multi-center, prospective, controlled trial comparing the new generation coils to standard platinum coils. Blinding, if at all possible, is preferable to minimize bias, at least for follow-up angiographic studies that should cover a period of 18 months. All patients with an intracranial aneurysm eligible for endovascular treatment would be proposed to participate. The study would enrol approximately 500 patients equally divided between the two groups, recruited within two years, to demonstrate a decrease in the recurrence rate, the primary outcome measure, from 20% to 10%. Secondary outcome measures should assure that complications, initial clinical and angiographic results remain unchanged. Independent data safety and monitoring committees are crucial to the credibility of trials and to ensure scientific rigor and objectivity. The scientific demonstration of an improved long-term efficacy, without significant compromise regarding safety, is mandatory before considering the widespread use of a new embolic device for the endovascular treatment of aneurysms. PMID- 20587222 TI - A randomized trial on the safety and efficacy of endovascular treatment of unruptured intracranial aneurysms is feasible. AB - SUMMARY: The safety and efficacy of endovascular treatment of unruptured intracranial aneurysms remain undetermined. A randomized trial may be the best way to demonstrate the potential benefits of endovascular management. We propose a randomized, prospective, controlled trial comparing the incidence of subarachnoid haemorrage of patients treated by endovascular coiling as compared to conservative management. We would also study a composite outcome combining SAH and the morbidity of treatment. All patients with one or more unruptured aneurysm >> 3 mm eligible for endovascular treatment would be proposed to participate. The study would be conducted in 40-50 centres. The entire study would enrol 1800 patients, recruited over three years and followed for five years, but would be preceded by a feasibility study on 200 patients. A randomized trial comparing endovascular and conservative treatment could have an important impact on the clinical management of intracranial aneurysms. PMID- 20587223 TI - A new sclerosing agent in the treatment of venous malformations. Study on 23 cases. AB - SUMMARY: Absolute ethanol is the most effective agent in the treatment of venous malformation (VM) although it is quite risky to use because of the danger of diffusion beyond the target. To reduce this risk, we have developed an alcoholic sclerosing solution that is less diffusible. The viscosity of absolute ethanol was enhanced with monographic ethyl-cellulose at a concentration of 5.88% ie 0.75 g in 15 ml of absolute ethanol 95%. 23 patients with VM located on the buttock (1), hand (2), leg (1) and face (19) were treated. A mean volume of 1.99 ml of the solution was injected directly into the VM. Each patient had an average of 2.8 procedures. Sixteen patients were done under general anaesthesia and seven with local anaesthesia. Evaluation was performed by the patient, the dermatologist of the treating multidisciplinary team and a dermatological group not involved in the treatment of the patients. Patients were evaluated after a mean delay of 24.52 months. Evaluation of the cosmetic result was made with a five point scale and the global result with a three point scale. VM pain was evaluated by the patients with a Visual Analogue Scale. The aesthetic results were graded as satisfactory (> 3) for the patient and the dermatologist of the multidisciplinary team. However the results were not as good with the independent dermatological group evaluation. The pain was significantly less important after the treatment (p << 0.001). Among the 23 patients, the local adverse events were nine necrosis with or without ethylcellulose fistula followed by only two surgical procedures. There were no systemic adverse events. Sclerotherapy of VM is usually performed with absolute ethanol or ethibloc. The main advantage of our sclerosing mixture is that it expands like a balloon when injected slowly in a aqueous media. Because of the important increase in viscosity the volume of injected solution is much lower than ethanol alone and the risk of systemic reactions is lower. Contrary to ethibloc, post-sclerosing surgery is not necessary because sub-cutaneous ethylcellulose disappears secondarily. PMID- 20587224 TI - Comparison of Endovascular and Surgical Treatment for Ruptured Cerebral Aneurysms with respect to Short and Long-Term Outcome. AB - SUMMARY: We compared the treatment for ruptured aneurysms from the clinical and radiological follow-ups after endovascular (GDC) or surgical treatment. There were 142 surgically treated cases and 38 endovascular treated cases from May 1997 to December 2001. In endovascular cases there were four A-com, four MCA, 12 ICA and 18 posterior circulation aneurysms. In surgical cases, there were 53 A-com ACA, 51 MCA, 36 ICA and two posterior circulation aneurysms. The clinical outcomes of endovascular and surgical treatments were correlated with the H & H grades before treatments. At short stage, 71% of endovascular and 78.2% of surgical cases showed a favorable outcome (GOS GR or MD) (p=0.3). Long-term clinical follow ups (14.5 to 58 months) showed 77.7% of endovascular and 87.7% of surgical cases resulted in GR or MD (p=0.17). In endovascular cases, 22.2% showed recurrence during the follow-up period and five of them needed re-treatment. We experienced failed endovascular approach at acute stage in seven cases which changed to surgery. In conclusion, the short and long term clinical results of endovascular treatment were acceptable comparing surgical clipping. High recurrence rate after GDC treatment did not permit future completeness of the treatment. Still the treatment alternative between endovascular or surgical treatment may change depending on the criteria of each institution, attention should be paid to the disadvantages of endovascular treatment as the first choice for ruptured aneurysms. PMID- 20587225 TI - Arterial dissection and subarachnoid haemorrhage in human immunodeficiency virus infected patients. A report of three cases. AB - SUMMARY: Cerebrovascular complications of AIDS have been reported as high as 34% in post mortem series. Most patients suffer from ischaemic strokes but there are a number of reports of patients presenting with subarachnoid haemorrhage (SAH) related specifically to aneurysm rupture. We present three patients with advanced HIV disease and low CD4 counts who present with SAH. In two of the patients the haemorrhage appeared to be caused by intracranial artery dissection which, to our knowledge, has not previously been described. Both patients were successfully treated endovascularly, one with segmental vessel trapping and the other with partial coil embolization of a false aneurysm. The pathological basis for HIV related arteriopathy is discussed in relation to these cases. PMID- 20587226 TI - Spontaneous petrous carotid artery occlusive dissection treated by local fibrinolysis and stent deployment. AB - SUMMARY: This paper reports a case of local thrombolytic therapy followed by stenting of the petrous carotid in a young woman with recurrent transient ischemic attacks from spontaneous dissection. A total of four overlapping balloon expandable stents were delivered in two different sessions one month apart. The procedure resulted in a potentially efficacious treatment for the prevention or reduction of cerebral damages from ischemia. At followup three months later the patient was symptomfree and DSA revealed a delayed proximal small pseudoaneurysm and a carotid-cavernous fistula. At one year follow-up the patient was still symptom-free with unmodified findings at cerebral angiography. PMID- 20587227 TI - Transvenous occlusion of a dural cavernous sinus fistula using a new expandable hydrogel-platinum coil (hydrocoil(r)). AB - SUMMARY: Hydrogel-coated platinum coils (Hydrocoils(R)) are currently under clinical investigation for their efficacy to improve anatomic results of endovascular occlusion of cerebral aneurysms. A case is presented in which this new expandable coil type was added to bare platinum coils in order to accelerate the transvenous occlusion of a dural cavernous sinus fistula (DCSF). A 53-year old woman presenting with mild left-sided eye redness and diplopia due to a DCSF (type D) underwent transvenous occlusion using bare platinum coils (Trufill(R)) and hydrogel coated coils (Hydrocoil(R)). After successful catherization of the cavernous sinus, bare platinum coils were densely packed and eventually combined with Hydrocoils(R) which resulted in immediate and complete occlusion of the fistula. No technical or clinical complication occurred. The new expansile hydrogel-coated platinum coil (Hydrocoil(R)) can be successfully combined with bare platinum coils to accelerate transvenous occlusion of an AV-shunting lesion. Controlled volume expansion after deployment of this device offers potential benefits for occlusion of dural arteriovenous fistulas in other locations or for parent vessel occlusions in the treatment of giant or large complex aneurysms. PMID- 20587228 TI - Use of neuroform stent in a patient with acute stroke caused by spontaneous petrous segment internal carotid artery dissection: a case report. AB - SUMMARY: Neuroform stents have been recently introduced for treatment of broad necked intracranial aneurysms. Several studies have demonstrated the feasibility of deployment of Neuroform stents (Boston Scientific Target, USA) in intracranial circulation. We report a case of a patient presenting with acute stroke due to occlusive petrous segment internal carotid artery dissection who was treated with a Neuroform stent. PMID- 20587229 TI - Cortical venous aneurysm isolated cerebral varix. AB - SUMMARY: Venous aneurysms so-called isolated cerebral varix, are known as a related pathology in arteriovenous malformations (AVM) due to the arterial pressure on venous drainage (16). They are also observed in combination with developmental venous anomalies (DVA) (2,4,8,15). However, isolated varix is a rare entity (1,7,11,13). They appear in most cases without neurological deficits. Some of the cases mimic a meningioma due to their manifestation in CT and MR imaging and their axial cortical localization. The case presented here is a isolated varix of a cortical vein located rostral to the motor strip. The patient was operated on successfully. The MRI and the histology of the case are presented. PMID- 20587230 TI - Letter to editor. PMID- 20587231 TI - In vitro and in vivo Studies of the Extent of Electrothrombotic Deposition of Blood Elements on the Surface of Electrolytically Detachable Coils. AB - SUMMARY: Endovascular treatment of intracranial aneurysms with electrolytically detachable coils is often claimed to be based on electrothrombosis, i.e. intra aneurysmal thrombus formation through applied direct current. Despite the fact that this concept was described more than a century ago, the significance of electrothrombosis in the endovascular treatment of aneurysms remains debatable. Apart from electrothrombosis, mechanical obliteration of the aneurysmal lumen might be one of the many possible mechanisms to explain why and how detachable coils are effective in preventing aneurysms from (re-)rupture. The purpose of this experimental study was to investigate to what extent direct current comparable to that used for coil detachment would influence the adhesion of cellular and liquid blood components to the surface of electrolytically detachable platinum coils. For the in vitro study, electrolytically detachable platinum coils of various types were exposed to stagnant heparinised blood for a total of 16 h, without or with applied direct current for 30 or 90 s (1 mA, 4-6 V, coil as anode). For the in vivo study, electrolytically detachable platinum coils were exposed to flowing blood for 180 s, without or with applied direct current (2 mA, 4-6 V, coil as either anode or cathode), without anti-coagulation and after intravenous administration of 5000 U Heparin and again after the intravenous administration of 500 mg Aspisol in addition to Heparin. After exposure to blood according to these different experimental protocols, the coils were fixed in formalin solution, gold coated and examined by scanning electron microscopy. Thrombus formation on the surface of all unfibred coils was thin and highly variable both from coil to coil, and on different areas of any given coil. The application of direct current minimally enhanced thrombus formation in stagnant blood in vitro, but not in vivo. The cellular and fibrin adhesions on the coil surfaces without and with applied current did not effectively increase the diameter or volume of unfibred coils. Coils with attached nylon fibres, however, proved to be highly thrombogenic without or with application of current. In fibred coils, surface adhesions without and with applied current were voluminous enough to effectively increase the diameter of the coil, potentially important for the process of endosaccular aneurysm occlusion. Electrothrombosis plays no role in the endovascular treatment of intracranial aneurysms with electrolytically detachable coils. This explains why platinum coils with non electrolytic detachment mechanisms show a similar efficiency and recurrence rate. PMID- 20587233 TI - Endovascular treatment of acute embolism of the major cerebral arteries. The value of balloon disruption of the embolus. AB - SUMMARY: This study evaluated: 1) the effect of recanalization on changing clinical outcome, 2) the relationship between dose of Urokinase (UK) and incidence of recanalization and intracranial haemorrhage, and 3) the efficacy and feasibility of balloon disruption (BD) in the treatment of acute cerebral embolism. Sixty-one patients with acute embolism of the major cerebral arteries treated by endovascular approaches over the past nine years were retrospectively evaluated. Among them, 30 cases were treated by BD alone or in conjunction with intra- arterial fibrinolysis in the last five years. The other 31 cases, mostly treated in the first four years, were treated with intra-arterial fibrinolysis alone and were used as controls to evaluate the efficacy of BD. Control angiography was performed just after the reperfusion procedure to evaluate the degree of recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical outcome was evaluated using modified Rankin Scale (mRS) score at the time of discharge. Thirty-six of the 61 patients (59.0%) achieved high-grade recanalization (TIMI grade 3). Significantly more patients attained favorable outcome (mRS score 0-1) in the high-grade recanalization group than the low-grade recanalization group (41.7% vs. 16.0%, p < 0.05). Concerning patients treated with BD, significantly more patients attained good recanalization and significantly more patients were ambulatory (mRS score 0-3) than those treated with intra-arterial fibrinolysis alone (76.7% vs. 41.9%, p < 0.01; 70.0% vs. 41.9%, p < 0.05, respectively). A significantly lower dose of UK was used, and relatively less intracranial haemorrhage was seen in patients treated with BD than those treated with intra- arterial fibrinolysis (194,000 +/- 191,000 units vs. 388,000 +/- 231,000 units, p=0.001; 16.7% vs. 38.7%, p=0.055, respectively). Concerning morbidity and mortality of BD, there was one death caused by dissection of the M2 portion of the middle cerebral artery (MCA) that happened during BD on a distally migrated embolus. Although no conclusions can be drawn from our study, a favorable outcome for acute embolism of the major cerebral arteries is expected by attaining good recanalization. In addition, BD is an effective technique that can achieve high grade recanalization alone, or reducing the dose of fibrinolytic agent. PMID- 20587232 TI - Local hyperthermia enhances thrombosis in aneurysms containing platinum coils. AB - SUMMARY: Despite recent technical advances in embolization of cerebral aneurysms with platinum coils, some aneurysms eventually resulted in incomplete packing with remnant neck or dome filling. Such a situation with a remaining inflow zone may pose a risk of rupture and subsequent regrowth. Metals characteristically generate heat under high-frequency alternating magnetic fields (AMF). We used this property to induce local hyperthermia and promote thrombogenesis in incompletely packed aneurysms. Glass model aneurysms packed with coils were subjected to AMF to investigate the correlation between weight of platinum and temperature elevation and the correlation between flow rates of water through the model and temperature elevation. Next, activated coagulation time (ACT) of blood obtained from dogs was studied at various temperatures. Finally, side-wall aneurysms created in the canine carotid artery using a venous patch were packed with platinum coils. Change in temperature and angiographic changes were investigated after AMF application. In the glass model, the weight of platinum was correlated with elevation of temperature, and a negative logarithmic correlation was evident between flow rate and elevation of temperature. Elevation of blood sample temperature tended to shorten ACT. In canine carotid aneurysms, elevation of intra-aneurysmal temperature was confirmed and sufficient elevation of temperature was found to promote angiographically evident thrombogenesis of the remnant space after AMF application. Local hyperthermia may be useful in completing luminal obliteration of aneurysms after coil embolization. It may particularly useful for ruptured aneurysms to prevent the early rerupture. PMID- 20587234 TI - Experimental determination of minimal stimulation current and period for electrical thrombosis in dogs. AB - SUMMARY: Endovascular surgery has been proposed as an alternative treatment for cerebral aneurysms. However, for wide neck and large sized lesions it is very difficult to obtain complete occlusion and tissue organization. The present study was conducted to examine the efficacy of electrical thrombosis for cerebral aneurysms and parent arterial occlusions using Interlocking Detachable Coils (IDCs), focusing on the minimum current volume and stimulation time required for stable electrical thrombosis formation. We used ten mixed-breed adult dogs (in the study body weights 9-12 kg; males: 5, females: 5). Guiding catheter sand microcatheters were introduced into both sides of the distal external carotid artery (ECA) and placed at the same level. To prevent migration, IDCs (4 mm x 12 cm) were placed in the ECA without being detached. After confirming no vessel occlusion, we applied a positive current (2-6 mA) to the coil on one side and performed angiography every ten minutes to observe whether vessel occlusion with electrothrombosis had occurred. It was determined that to achieve complete occlusion of the external carotid arteries in mixedbreed dogs, a minimum stimulation current of 4mA and a minimum stimulation time of ten to 20 minutes are required. PMID- 20587235 TI - "Mirror" aneurysms involving the bilateral distal posterior cerebral artery. A case report of endovascular treatment and literature review. AB - SUMMARY: We report the case of patient with bilateral and symmetrical aneurysms, mirror image, of the distal posterior cerebral artery (PCA) who presented with subarachnoid haemorrhage. The aneurysms were treated by endovascular approach using Guglielmi detachable coils (GDCs). A review of the pathophysiology, clinical manifestations and management of mirror aneurysms is presented and discussed. PMID- 20587236 TI - Relevance of occlusion test in endovascular coiling of posterior cerebral artery (p2 segment) aneurysms. AB - SUMMARY: P2 segment aneurysms are located on the posterior cerebral artery (PCA) between the junction of the posterior communicating artery with the PCA and the quadrigeminal cisternal part of the PCA. We reviewed our experience with endovascular coiling in such aneurysms. Clinical and pre-procedural data from four patients, referred for endovascular treatment of P2 segment aneurysms, were retrospectively studied for factors influencing post-interventional neurological deficits caused by ischemia of the PCA distal territory. Balloon occlusion was done in three patients and patient tolerance was assessed using clinical and anatomic criteria. Embryologic and anatomic features of the PCA were reviewed. Balloon occlusion test and endovascular coiling of aneurysms was possible in three patients. Control angiogram after embolization showed elimination of aneurysms from the circulation and the distal PCA filled through leptomeningeal anastomoses. One patient deteriorated due to aneurysmal rupture soon after the balloon occlusion test and coiling could not be done. In the other three patients post-intervention CT and MRI images showed PCA territory infarcts in spite of demonstration of good collateral circulation distal to the occluded PCA. In conclusion, P2 aneurysms can be effectively treated by endovascular coiling without a balloon occlusion test. While the balloon occlusion test does not contribute to clinical decision-making it may be associated with potential morbidity and mortality. PMID- 20587237 TI - Takayasu arteritis with multiple intracranial aneurysms. A case report. AB - SUMMARY: A rare case of multiple cerebral aneurysms associated with Takayasu aortitis is reported. Only seven cases have been reported so far, all of which are from Japan. This is the first case with this association being reported from India. A 50-year-old hypertensive woman developed sudden onset severe headache and loss of consciousness. CT scan revealed subarachnoid haemorrhage in the suprasellar cisterns and mild hydrocephalus. The patient on admission had a rebleed producing a massive subarachnoid haemorrhage. Angiogram revealed occlusion of bilateral vertebral arteries and right common carotid artery. The left carotid artery was ectatic with saccular aneurysms in the ophthalmic segment and communicating segment. Aortogram showed the radiological picture of Takayasu arteritis Type III. Surgical clipping of the aneurysms was performed. However, the patient developed a massive right cerebral infarct in the postoperative period following which she expired. Abnormal haemodynamics in the overloaded cerebral circulation rather than primary arteritic involvement of intracranial vessels appears to be the cause of aneurysm formation. PMID- 20587238 TI - Spontaneous Thrombosis of a High-flow Carotid-Cavernous Fistula after Failed Transarterial Balloon Occlusion. AB - SUMMARY: A 62-year-old man with a traumatic high-flow right carotid-cavernous fistula was treated by transarterial balloon occlusion technique. However, because of the relatively small size of the fistula, the balloon could not enter into the cavernous sinus via the fistula. During the procedure, the shunt flow decreased significantly, and we stopped the procedure. Follow-up angiography performed 14 days after the procedure showed complete occlusion of the fistula with a small residual pseudoaneurysm. One year later, the pseudoaneurysm had decreased in size. Repeated transient decrease and stagnancy of blood flow at the fistula during the balloon procedure may have played an important role in the thrombosis in this patient. PMID- 20587239 TI - Emergency Extracranial-to-Intracranial Bypass after Thromboembolic Occlusion of the Middle Cerebral Artery Following GDC Embolization of a Ruptured ACoA Aneurysm. AB - SUMMARY: We report a case of thromboembolic occlusion of the middle cerebral artery after endovascular treatment of a ruptured anterior communicating artery aneurysm. When fibrinolytic therapy failed to recanalize the occluded vessel, an emergency extracranial-to-intracranial bypass was performed. This intervention rescued our patient from cerebral infarction. This case demonstrates the importance of the offering this procedure at neurointerventional centers. PMID- 20587240 TI - Regression of a Flow-Related Ophthalmic Artery Aneurysm After Treatment of a Frontal DAVS. A Case Report. AB - SUMMARY: We report a case of a frontal dural arteriovenous shunt or fistula (DAVS) adjacent to the left side of the cribriform plate, with bilateral supply from multiple arteries, the most prominent being the dural branches originating from the anterior ethmoidal artery coming from the left ophthalmic artery. Before treatment there was an eight mm flow-related arterial aneurysm proximally on the left ophthalmic artery. After transarterial embolization of the DAVS with N-butyl cyanoacrylate and polyvinyl alcohol, minimal shunting still remained. At follow up angiography six months after the treatment, the shunt was obliterated and the ophthalmic artery aneurysm had regressed completely. Our case illustrates that complete obliteration of a DAVS may be achieved even though arteriovenous shunting remains at the end of the procedure. Furthermore, a flow-related arterial aneurysm, may not warrant any specific treatment. Elimination of the high flow situation can lead to complete regression of these aneurysms. PMID- 20587241 TI - Acute severe epistaxis due to iatrogenic maxillary pseudoaneurysm. Emergency control of haemorrhage by carotid compression and early recurrence after coil embolization. AB - SUMMARY: Internal maxillary arterial or branch transection is a potential complication of maxillofacial surgery. We describe one such patient who developed acute massive nasal haemorrhage, an episode of which was controlled clinically just prior to performing endovascular embolization by employing the simple but effective clinical manoeuvre of manual carotid arterial compression. Six weeks later the haemorrhage recurred despite a seemingly adequate embolization of the affected arteries with microcoils and Spongistan due to re-establishment of flow through the coils. PMID- 20587242 TI - Treatment for intracranial cerebral artery stenosis. AB - SUMMARY: Symptomatic intracranial cerebral artery stenosis is largely resistant to drug treatment. Regardless of their locations, lesions may cause cerebral infarction with a frequency of 7-10% in a year, but the natural history of asymptomatic intracranial cerebral artery stenosis remains unclear. Revascularization is indicated for symptomatic lesions which show resistance to drug treatment, while bypass surgery is the accepted therapeutic indication for haemodynamic ischemia. Endovascular treatment is effective in haemodynamic ischemia, and is also expected to be effective against embolic symptoms. Bypass surgery for anterior circulation cases is safe because of its low incidence of complications, whereas bypass surgery for posterior circulation cases is technically difficult and has a high associated complication rate. Hence, endovascular treatment is currently favored for posterior circulation cases, and has also been introduced for anterior circulation cases. Endovascular treatment has become a widespread modality for intracranial cerebral artery stenosis, but there are many unsolved problems associated with complications, technology and devices. Therefore, in practice, endovascular treatment should be used only with a strict indication, and should be performed only after considerable thought and with appropriate informed consent. PMID- 20587243 TI - Percutaneous transluminal angioplasty for atherosclerotic stenoses of intracranial vessels. AB - SUMMARY: To study the efficacy and long-term outcome of percutaneous transluminal angioplasty (PTA) with/without stent placement for intracranial atherosclerotic stenoses, we reviewed our treated cases retrospectively. Between May 1992 and October 2003, PTA with/without stents was performed in 64 intracranial and skull base vessels in 62 patients, including 24 middle cerebral arteries, 16 internal carotid arteries, 13 vertebral arteries, and 11 basilar arteries. PTA was technically successful in 55 vessels (86%). However, four vessels (6%) failed to achieve satisfactory dilatation. We encountered five periprocedural strokes as symptomatic complications, for a mortality rate of 4.7% and a morbidity rate of 3.1%. All the patients with stent placements survived angioplasty without any complication. In the clinical follow-up available for one week to 11.5 years (mean, 4.7 years), there were three strokes related to the treated vessels. The annual stroke rate in the affected territory was estimated at 1.2% per year. According to these results, PTA for intracranial atherosclerotic stenoses seems to be a beneficial therapy for immediate anatomical results and long-term stroke prevention. Stent-assisted PTA could help patients achieve successful dilatation and avoid complications. PMID- 20587244 TI - Clinical results of percutaneous transluminal angioplasty and stenting for intracranial vertebrobasilar atherosclerotic stenoses and occlusions. AB - SUMMARY: Eighteen patients with intracranial vertebrobasilar stenosis and occlusion were treated by PTA or stenting. In 11 of 18 cases, only PTA was performed and in seven of 18 cases, we used stents. The mean stenosis before and after PTA/stenting was 82.8% and 22.3%, respectively. In 11 cases of PTA only, the stenotic rate decreased from 81.8% to 29.6%, while 85.0% of the stenotic rate remarkably reduced to 6.0% in seven cases of stenting. The 30 days morbidity and 30 days mortality rate were 5.5% and 5.5%, respectively. There was only one haemorrhagic complication (cerebellar haemorrhage) in cases of stenting, and no ischemic events during or after the procedures. Restenosis (more than 50% stenosis) occurred in four of 18 cases(22.2%) during mean followup period of 12 months. Two patients with VA occlusion before treatment, developed restenosis and reocclusion. Complete total occlusion seems to be a high-risk lesion and strict follow-up is required. In this study, PTA/stenting for intracranial vertebrobasilar artery stenosis or occlusion is an effective treatment, but strict indications may be required because procedure-related 30 days morbidity rate was 5.5% in addition to unclear natural history. PMID- 20587245 TI - Treatment of cervical carotid artery stenosis. AB - SUMMARY: As treatment for cervical carotid artery stenosis, medical treatment, carotid endarterectomy (CEA), and percutaneous transluminal angioplasty (PTA) with/without stenting are known. In this report, we review the history and current status of these treatments. Comparison between CEA and PTA/stenting is further discussed based on recent clinical reports and evidence. PMID- 20587246 TI - Technique and Clinical Results of Carotid Stenting under Distal Protection. AB - SUMMARY: We perfomed carotid artery stenting(CAS) in 215 patients from August 1997 to October 2003 mainly using the distal protection technique. Our technique and clinical results are described in this paper. PMID- 20587247 TI - Early treatment for ruptured cerebral aneurysms. Location of aneurysms and choice of treatments. AB - SUMMARY: The purpose of this study was to evaluate the effect of endovascular treatment with Guglielmi detachable coils (GDC) on the outcomes of subarachnoid haemorrhage (SAH) patients of poor grades and high ages for each location of aneurysms. Between 1990 and 2003, 529 SAH cases underwent angiograghy as candidates of early aggressive treatment in our hospital. For the 299 cases in 1990-96 (Group 1), treatment options were early and intensively delayed craniotomy surgery and conservative management, while for the 230 cases in 1997 2003 (Group 2), GDG embolization at acute stage was added to these three treatment options. We compared clinical courses and outcomes of the poor grade (Hunt & Kosnik Grade 4-5) patients and high age (>=70 years old) patients between two groups for each location of aneurysms. Introduction of GDC embolization expanded the indication for early treatment in the poor grade patients with anterior communicating artery aneurysm (A-Comm An), the high age patients with internal carotid artery aneurysm (IC An) and all patients with Basilar bifurcation aneurysm (BA-Top An), and has contributed to improvement of their outcomes. To the poor grade patients with middle cerebral artery aneurysm (MCA An), GDC embolization was hardly indicated, because haematoma evacuation concomitantly performed with aneurysm occlusion would be necessary for those patients. In conclusion, results of treatment with GDC embolization at an acute stage are desirable for poor grade patients with A-Comm An, aged patients with IC An and all patients with BA-Top An. The indication of GDC embolization for the patients with MCA An is limited. PMID- 20587248 TI - Endovascular surgery as the first-choice treatment for ruptured cerebral aneurysms: how far has it come? AB - SUMMARY: One hundred and seventy patients with ruptured cerebral aneurysms were treated by coil embolization from September 1997 to December 2002. After January 2000, coil embolization was selected as the first-choice treatment for ruptured aneurysms. During this period, the authors investigated the number of aborted cases, the number of complications, and how many patients could be treated by coil embolization according to the locations of ruptured cerebral aneurysms. One hundred and ninety-five sessions were performed on 170 patients, and 13 sessions (6.7%) were aborted mainly because of the difficulty of the approach and the wide necks of the aneurysms. In four patients, although procedural perforation and haemorrhage occurred, the outcome was good or excellent. Eight poorgrade patients experienced haemorrhage after coil embolization and seven patients died. The volume embolization ratios of small and large aneurysms were 27% and 21%, and the recanalization of small and large aneurysms occurred in 9% and 38% of patients, respectively. From January 2000 to December 2002, 119 (66%) of 180 ruptured cerebral aneurysms were treated by coil embolization. According to the location of aneurysms, 89% vertebrobasilar, 87% anterior cerebral, 65% internal carotid and 24% middle cerebral artery aneurysms could be treated by coil embolization. Because the tight packing of large aneurysms was difficult, the recanalization rate of large aneurysms was high. However, the results of small aneurysms were satisfactory. Almost 90% of vertebrobasilar and anterior cerebral artery aneurysms could be treated by coil embolization. PMID- 20587249 TI - Clinical Outcomes of Coil Embolization for Acutely Ruptured Aneurysm. Comparison with Results of Neck Clipping when Coil Embolization is Considered the First Option. AB - SUMMARY: The purpose of this prospective study was to evaluate clinical results in patients with acutely ruptured cerebral aneurysm treated by neck clipping (NC) or coil embolization (CE) when CE was considered the first option. Between 1998 and 2003, 280 patients with acutely ruptured cerebral aneurysms excluding intracerebral hematoma were evaluated. Patients were managed prospectively according to the following protocol: primary treatment modality was CE (n=179). NC (n=101) was selected for the patients with aneurysms that were small (less than 2 mm) or an unsuitable shape for CE. Surgical complication rates were 4.5% for CE and 16.8% for NC. Symptomatic vasospasm occurred in 8.4% of CE patients and 29% of NC patients. Good recovery on the Glasgow Outcome Scale was achieved by 71% of CE patients and 50% of NC patients at discharge. Surgical complications and symptomatic vasospasm were significantly reduced in CE compared to NC. Clinical outcome at discharge was also better with CE. Although 18.3% of CE patients showed various degrees of aneurysmal recanalization and 7% of CE patients required additional treatment (re-CE or NC), aneurysmal rebleeding occurred in only one patient during followup (mean, 3.95 years). PMID- 20587250 TI - Embolization of Arteriovenous Malformation. Efficacy and Safety of Preoperative Embolization Followed by Surgical Resection of AVM. AB - SUMMARY: Treatment options for cerebral arteriovenous malformation (AVM) are still controversial due to the recent result of stereotactic radiosurgery and the improved result of microsurgical resection. We investigated previously treated AVM cases and discussed the efficacy and safety of preoperative embolization especially for microsurgical resection of high-grade AVM in the Spetzler-Martin grading. Efficacy of preoperative embolization was evaluated based on 126 previously treated AVM cases at Shinshu University Hospital during the last 25 years. The safety of embolization was evaluated based on our previously-embolized 58 AVM cases (91 procedures) in the last 11 years after introduction of preoperative embolization for AVM. In all 126 cases, 82 were treated before introduction of embolization and 44 were treated after introduction of embolization. In 82 cases of the pre-embolization era, 63 lesions were removed totally in 63 AVMs (77%), partially resected in 11 (13%) and untreated in eight (10%). In 74 surgically removed cases, 11 (15%) cases showed severe intra/postoperative bleeding. In 44 cases of the embolization era, lesions were removed totally in 29 AVMs (66%), disappeared only with embolization in one (2%), disappeared with radiosurgery in seven (16%) and were untreated in five (11%). In 32 surgically removed cases, only one (2%) case showed severe intra/postoperative bleeding. In all 58 embolized cases, 44 were surgically removed, six were treated with radiosurgery, one was eliminated with embolization alone and six were partially obliterated and followed up for their location. In 91 procedures for 58 cases, two haemorrhagic and three ischemic complications occurred, three were transient and two remained having neurological deficits. The introduction of preoperative embolization improved the total removal rate and reduced the intra/postoperative bleeding rate in surgical removal of AVM. The total risk of embolization is low and well-designed preoperative embolization makes surgical resection safer even in high-grade AVM in the Spetzler-Martin grading. PMID- 20587251 TI - Complications of embolization for cerebral arteriovenous malformations. AB - SUMMARY: Embolization is recognized as an important adjunct in the treatment of cerebral arteriovenous malformations (AVMs). We reviewed our results of embolizations for AVMs and discussed procedure-related complications. Eleven complications were recorded in 68 consecutive patients (16%). Of these, four were technical problems including a glued catheter, inability to withdraw the catheter, vessel perforation by the microcatheter, and coil migration. Other complications included three cases of ischemic symptoms due to retrograde thrombosis, two cases of asymptomatic cerebral infarction, one case of asymptomatic small haemorrhage due to venous occlusion, and one case of post embolization haemorrhage of unknown etiology. Our morbidity rate was 7%, mortality rate was 0%, and asymptomatic complication rate was 9%, retorospectively. Further improvements to endovascular techniques and devices are required. PMID- 20587252 TI - Efficacy and limitations of the neuroform stent system for intracranial aneurysms. AB - SUMMARY: We performed aneurysm embolization in seven patients using a self expandable Neuroform stent (Boston Scientific/Target, Fremont, CA) and coils to cover the aneurysm neck and fill the aneurysm sac. Seven patients with an average age of 45 were treated in the period from October 2002 to July 2003. The aneurysm lesions involved the basilar trunk in one case, the basilar-superior cerebellar artery in one case, the internal carotid artery in four cases, and the middle cerebral artery in one case. The ruptured lesions involved the internal carotid artery in one case and the middle cerebral artery in one case. We used a Neuroform stent measuring 4.5 x 20 mm in four cases, 4.5 x 15 mm in two cases, 3.5 x 20 mm in one case, and 3.5 x 15 mm in one case. We performed aneurysm coil embolization after Neuroform stenting in all cases without development of neurological deficits caused by the interventional procedure. In performing these procedures, we investigated the efficacy and limitations of the Neuroform stent system for intracranial aneurysms. The advantages of Neuroform self-expanding stents include better flexibility and adaptability to different vessel sizes, but this stent system presents various technical difficulties during delivery. PMID- 20587253 TI - Assessing Prognosis of Areas of Acute Cerebral Ischemia Using Perfusion CT. AB - SUMMARY: Vascular recanalization by the vascular reconstruction method can dramatically improve ischemic symptoms in patients with acute cerebral ischemia. However, this treatment method is frequently associated with haemorrhagic complications. The indications for this therapeutic approach have been described in a number of studies in the literature. The present paper discusses the possibility of assessing the prognosis of ischemic areas using perfusion CT (PCT) by comparing the results obtained before and after thrombolytic therapy. Twenty six patients underwent vascular reconstruction at our hospital between July 2002 and March 2004. Of these patients, six who underwent PCT before treatment and showed adequate recanalization following vascular reconstruction were included in the present study. PCT images were obtained using the first-pass bolus-tracking method with a 16-row multislice helical CT scanner. Areas of cerebral ischemia were evaluated by CT before and after vascular reconstruction. A region of interest was placed in the area showing low density in CT images before vascular reconstruction. The mean average CBF (mL/min/100 g), CBV (mL/100 g), and MTT (s) values were calculated in areas with and without cerebral infarction after vascular reconstruction. The %CBF, % CBV, and %MTT values relative to the normal side were evaluated with reference to the time until recanalization. Transarterial vascular reconstruction resulted in full recanalization in four patients and partial recanalization in two. The mean time from onset to recanalization was 284.7 +/- 63.27 minutes and was not longer than six hours in any patient. The patient prognosis results in terms of GOS were GR in two patients, MD in three patients, and SD in one patient. Based on comparison of the time after examination to recanalization, the %CBF showed a significant positive correlation in the salvaged area (Y = 47.321 + 2.491 x %CBF:R(2) = 0.792, p < 0.05). A significant correlation was not observed in %CBV, but %MTT showed a significant negative correlation (Y = 269.45 - 0.356 x %MTT:R(2) = 0.794, p < 0.05). The %CBF and %MTT results obtained by PCT performed before transarterial vascular reconstruction suggest that it may be possible to estimate the time before vascular reconstruction and the relationship with prognosis. These findings are expected to help ensure the appropriate application of vascular reconstruction and to provide useful information for developing optimal therapeutic protocols, thus reducing complications. In addition, because the results are based on the time after examination, the appropriate therapeutic approach can be determined even when the time of onset of ischemia is uncertain. PMID- 20587254 TI - Simulation Study of Distal Balloon Protection Systems during Carotid Artery Stenting. AB - SUMMARY: The purpose of our experimental study was to assess the pitfalls of distal balloon protection systems and to learn any technique tips to increase safety. Silicone carotid artery models were connected to a circulatory system to simulate arterial flow. A distal balloon protection device, PercuSurge GuardWire Plus (GWP, Medtronic Vascular) was delivered to the internal carotid artery (ICA), then was inflated to occlude ICA flow temporarily. A debris aspiration catheter (Export catheter) was delivered just proximal to the GuardWire Plus balloon coaxially, in order to introduce and diffuse particulate debris (20 500micro meter in diameter) in the ICA stump. Then, after debris in the stump was aspirated, the GWP balloon was deflated. We recorded all the processes of our simulation experiments on a digital video and observed the movements of debris during these experiments. Exp 1) We simulated the movements of debris in the ICA stump when the GWP balloon was gradually deflated to produce a crevice between the balloon and vessel wall, simulating accidental movement of the GWP balloon during the procedure. Exp 2) In order to assess the optimal placement of the tip of aspiration catheter, the debris in the ICA stump was aspirated from three different sites(from just below the GuardWire balloon, from 2cm below it, and from 5cm below it). Exp 1) When the crevice appeared between GuardWire balloon and silicone tube, simulated debris began to concentrate just below the balloon. Then, some debris migrated distally from the crevice, and another part crowded in the crevice so that was impossible to aspirate and migrated in the end. Exp. 2) Debris aspiration was most effective from immediately below the GuardWire balloon, and the aspiration ability declined as the distance between the balloon and aspiration catheter became longer. According to our simulation studies, when the GWP balloon was moved accidentally during CAS procedures, or when the aspiration catheter was not delivered all the way to the GuardWire Plus balloon, distal embolization might still occur, even under protection. PMID- 20587255 TI - Impact of stent design on intra-aneurysmal flow. A computer simulation study. AB - SUMMARY: In addition to providing a skeleton for vessel reconstruction, stent implantation as used for cerebral aneurysm treatment can induce flow redirection, thus reducing vortical flow velocities within the aneurysm cavity. Further, stent characteristics such as strut size, porosity and cell shape influence the changes in intra-aneurysmal flow by analog simulations. The purpose of this computer simulation study was to visualize the flow pattern over the entire neck area of a side wall aneurysm while changing the stent parameters. A 3-D computer model aneurysm was constructed to have a parent artery of 5 mm diameter and an aneurysm of 10 mm diameter. The distance between the midline of main artery and center point of the aneurysm was 6.8 mm, providing a neck length of 5 mm, a width of 3.6 mm, and a neck area of 14 mm 2. The simulations were carried out with a Finite Element Method based flow simulation package. The incompressible Navier-Stokes equation was solved for a steady flow with a mean speed of 290 mm/s, steady viscosity of 3.83 cp, and density of 1.0 g/cm3. Two parallel stent struts (dimensions: 100 mum m 100 mum m 2.0 mm) were introduced into the plane of the aneurysm neck. The fraction of the aneurysm neck cross-section occupied by the stent was 2.83% in all cases. The velocity distribution through the neck of the aneurysm was calculated for three different choices of separation between the struts for each of two orientations of the struts (parallel and perpendicular) relative to the vessel axis. The flow pattern in the aneurysm was composed of an inflow zone at the distal neck and of an outflow zone at the proximal neck. The placement of stent struts at the aneurysm neck resulted in a decrease in the mean speed in the aneurysm. The degree of reduction and the distribution of flow through the neck did depend on the orientation of the stent struts. The struts, when placed parallel or perpendicular to the parent vessel axis affected the mean speed through the aneurysm neck differently. PMID- 20587257 TI - Embolization of the Middle Meningeal Artery for Refractory Chronic Subdural Haematoma. Usefulness for Patients under Anticoagulant Therapy. AB - SUMMARY: Endovascular embolization of the middle meningeal artery was performed in two cases of refractory chronic subdural haematoma (CSDH) after repeated burr hole and irrigation surgeries. The embolization prevented expansion of the CSDH in both cases, and the haematoma disappeared completely in one case. The expansion of CSDH is considered to result from repeated bleeding from the macrocapillaries on the haematoma capsule. Embolization of the middle meningeal artery appears to be useful to eliminate the blood supply to this structure. PMID- 20587256 TI - Feasibility of photocrosslinkable chitosan as an embolization material for aneurysms. Biological reaction after aneurysm embolization. AB - SUMMARY: The purpose of this study was to evaluate the feasibility of photocrosslinkable chitosan as an embolization material for aneurysms. Three experimental aneurysms were created in three Japanese white rabbits. All of the aneurysms were packed with chitosan hydrogel. Histopathologic data were analyzed on two, seven, and 30 days after embolization. Unorganized clots and minimal inflammation around the applied chitosan hydrogel were observed two days after implantation. After seven days, the chitosan was reduced and inflammatory response appeared. At 30 days, most of the aneurysm lumen was replaced with inflammatory cells, and the remaining chitosan was not observed. Severe complications such as anaphylaxis did not occur after the embolization with the chitosan. These results suggest that photocrosslinkable chitosan might be a candidate for an embolization material for endovascular treatment of cerebral aneurysms. PMID- 20587258 TI - Basi-Parallel Anatomical Scanning (BPAS) - MRI: a Simple and Useful MRI Technique for Pre-Procedural Evaluation in Cases of Basilar Artery Occlusion. AB - SUMMARY: Basi-parallel anatomical scanning (BPAS)-MRI is a simple MRI technique that we designed to reveal the surface appearance of the vertebrobasilar artery within the cistern. Because it requires only 2 cm-thick heavily T2-weighted coronal imaging with gray-scale reversal, we can obtain BPAS-MRI with any MR machine of any company. BPAS-MRI can easily show the outer contour of the vertebrobasilar artery even if occluded. Therefore, BPAS-MRI can also reveal the occluded basilar trunk and the shape of basilar top branching that we cannot see with any other imaging modality before the recanalizing interventional procedure. To avoid a dangerous blind manipulation of guidewires or micro-catheters, BPAS MRI should be obtained prior to the interventional procedure in cases of acute basilar artery occlusion. PMID- 20587259 TI - Computational fluid dynamics for brain circulation and aneurysm with therapeutic devices. AB - SUMMARY: We analysed fluid dynamics at brain arteries having multiple inflow and out flow like Willis ring based on clinical imaging modalities. In addition, we analysed fluid dynamics with therapeutic devices like coils and stents to simulate their influences to blood flow. 3D CTA and MRA obtained three dimensional structures of the brain vessels. The centreline was obtained from the three dimensional structure. Diameter of the blood vessels was measured by 3D CTA/MRA then smooth surfaced blood vessel models were created. For the fluid analysis, we developed a home brew software which can display parameters such as streamline, etc. In addition, our CFD (computational fluid dynamics) software can work in collaboration with a CAD (computer aided design) software which we also developed (VCAD: Volume CAD). So, therapeutic devices such as coils, balloons and stents could be placed in the models and CFD analysis could be performed placing devices in the models. The flow pattern in the complicated vascular structure could be calculated such as Willis ring which has multiple inputs like ICA, VA and multiple outlets like MCA and PCA with communicating arteries. CFD with therapeutic devices could also analysed with our system. CFD including communicating arteries will assist the simulation of parent artery occlusion. CFD with therapeutic devices is helpful not only for simulation for embolization, but will help us to design therapeutic devices under computer simulation. PMID- 20587260 TI - Fibered electrolytically detachable platinum coils used for the endovascular treatment of intracranial aneurysms. Initial experiences and mid-term results in 474 aneurysms. AB - SUMMARY: Between 1992 and 2003, a total of 2029 aneurysms in 1748 patients were treated by endovascular occlusion with electrolytically detachable coils. In this series, electrolytically detachable platinum coils with Nylon fibers (Sapphire Detachable Coil System, MTI, Irvine, CA, USA) were used in 474 aneurysms solely or in combination with bare coils from various manufacturers. To determine the safety and clinical efficacy of Nylon fibered coils for the endovascular treatment of intracranial aneurysms in comparison to bare platinum coils a thorough retrospective statistical analysis by means of logistic regression and matched pairs analysis was performed. Only treatments with data for all matching variables were used, resulting in 421 matched pairs. The analysis was performed with respect to clinical status and numerous parameters concerning individual aneurysm characteristics (e.g., location, neck width, fundus diameter). Treatment related parameters included the use and percentage of fibered coils, occlusion rate, procedural complications, early clinical outcome and Glasgow Outcome Scale (GOS) scores. Finally, long-term follow-up results (particularly recurrence, cause of recurrence and post treatment haemorrhage) were evaluated. Both logistic regression and matched pairs analysis showed a statistically improved occlusion rate if fibered coils had been used (96% largely occluded with the use of fibered coils vs. 84-85% with the exclusive use of bare coils). However, the amount of fibered coils calculated as percentage of coil length did not seem to have significant impact. Procedures with fibered coils did not lead to a higher rate of thromboembolic events (8.0% for fibered vs. 10.5% for bare coils).The apparently better clinical outcome in the group treated with fibered coils determined by both postprocedural outcome and GOS, did not reach statistical significance. Analysis of the anatomical properties showed no differences between the groups treated with bare and fibered coils in terms of neck width, fundus diameter, and anatomic location. As expected, a higher occlusion rate was achieved in aneurysms with smaller neck and fundus independent from the type of coil used. On follow up angiography, there was an apparently lower rate of recurrence secondary to coil compaction in the group treated with fibered coils, but these data were compromised by the fact that up to date only about one third of 474 aneurysms treated with fibered coils had undergone angiographic follow-up and this did not reach statistical significance. From our experiences, we conclude that the use of fibered electrolytically detachable platinum coils in aneurysm treatment leads to significantly improved occlusion rates compared to the sole use of bare platinum coils. We hope that with increasing follow-up data we will be able to confirm that the apparently reduced recurrence rates for aneurysms treated with fibered coils can be proven with statistical significance. PMID- 20587261 TI - Hereditary Haemorrhagic Telangiectasia Cerebrospinal Localization in Adults and Children. Review of 39 cases. AB - SUMMARY: Cerebral arteriovenous malformations (CAVM) can be associated with Hereditary Haemorrhagic Telangiectasia (HHT), a dominantly inherited vascular disorder with variable penetrance and expressivity. The presentation and angiographic features were analysed retrospectively. The purpose is to point to special groups of AVM patients within the overall CAVMs and to discuss the issue of screening. We reviewed 34 cases of HHT-related CAVM from the data bank in Bicetre from 1985-2003. In Spinal cord AVM (SCAVM) there were 194 patients with 5 HHT. HHT was diagnosed when at least two criteria were met; cutaneous telangiectasia, epistaxis, visceral AVMs, angiographic findings of AVF and first degree family history. Intracranial haemorrhage was the presenting symptom in 8.8% and the risk of haemorrhage in the natural history was 0.7% per year. The commonest angiographic features in adults are nidus(81.8%) and multiplicity(45.5%), while in the paediatric group venous ectasia and giant pouches(91.3%), AVF(69.6%) and multiplicity( 52.2%). In spinal cord lesions macrofistulas are demonstrated in 83% of HHT with no multiplicity. HHT-related CAVMs present as multiple lesions, cortical in location, micro AVMs or AVF. HHT in SCAVM is expressed as single macro AVF, especially in the paediatric group. AVF in children are highly suggestive of HHT. We do not recommend screening in HHT adult patients for CAVM, while in the paediatric population, screening could be recommended at six months of age for cerebrospinal localization. These patients should be screened for Pulmonary AVF, which needs to be treated in priority. PMID- 20587262 TI - Embolization of vascular malformations in head and neck regions. A single center experience. AB - SUMMARY: The purpose of this study is to determine the effectiveness of embolization of each type of vascular malformation. Thirty three patients with a diagnosis of vascular malformations in head and neck regions who were treated by embolization at Siriraj Hospital, Thailand, between 1997-2002 were reviewed retrospectively. There were 19 arteriovenous malformations (AVMs), two arteriolar capillary types, ten venous malformations, one veno-lymphatic malformation and one mixed capillary and venous types. The goal of treatment is to restore function and to prevent bleeding complications with particularly good cosmetic results. The technique and therapeutic agents depended on the types and flow characteristics of each malformation. Transarterial embolization with N-butyl cyanoacrylate were used in AVMs, unless no arterial route approach, then direct puncture was tried. This was carried out in five patients with AVMs. Polyvinyl alcohol was used in two capillary lesions. All venous malformations were treated by absolute alcohol injection, percutaneously. All had good outcome without serious complications. Two patients had further plastic surgery, one was AVM of eyelid and the other was facial venolymphatic malformation. Embolization is considered to be the primary treatment by eradication of those abnormal vessels directly at the target, whereas delayed plastic surgery may be needed later. PMID- 20587263 TI - GDC Embolization of Intracranial Aneurysms with SAH and Mass Effect by Subdural Haematoma. A Case Report and Review. AB - SUMMARY: A 43-year-old woman was brought to the emergency room due to the sudden onset of severe headache and stuporous consciousness. She had no history of head injury. Computerized tomography scan revealed subarachnoid haemorrhage and left SDH with midline shift of about 10 mm. Cerebral angiography demonstrated anterior communicating artery and right middle cerebral artery bifurcation aneurysms. Her family refused operation due to her religion never to permit blood transfusion. So just aneurysm coiling and medical ICP control was planned. Guglielmi detachable coil (GDCs) embolization of the two aneurysms was successfully performed. She made a neurological recovery after embolization without evacuation of the SDH. She was discharged from hospital with no neurological deficit on day 21. We report our experience of successful GDC embolization on multiple aneurysms without craniotomy even in the selected case of mass effect. PMID- 20587264 TI - Ruptured intrasellar superior hypophyseal artery aneurysm presenting with pure subdural haematoma. Case report. AB - SUMMARY: Subdural haemorrhage from a ruptured intracranial aneurysm is a well known entity when associated with subarachnoid haemorrhage. However, haemorrhage confined only to the subdural space is rare because there are limited anatomical sites where extravasation can be purely subdural. We report the rare case of a patient who suffered pure subdural haematoma after the rupture of a left superior hypophyseal artery aneurysm located within the sella turcica. The patient was treated with endovascular coil embolization of the aneurysm. Angiography immediately after treatment and one month later revealed complete obliteration of the aneurysm. Six months after treatment, the patient remained symptom free. PMID- 20587265 TI - Dural Arteriovenous Fistula within the Hypoglossal Canal Successfully Treated by Transvenous Embolization. Case Report. AB - SUMMARY: We report a case of dural arteriovenous fistula (DAVF) within the left hypoglossal canal in a 64-year-old man who presented with tinnitus and ocular symptoms. Angiography revealed DAVF with the fistulous pouch medial to the left jugular bulb. The fistula was feeded by meningeal branches of the bilateral ascending pharyngeal arteries and the branches from the left vertebral artery. The fistula shunted into the left jugular bulb, with reflux into the left inferior petrosal (IPS) and cavernous sinuses (Cses), left superior ophthalmic vein (SOV) and cortical veins over the cerebral convexity. We performed transvenous coil embolization to occlude the fistula resulting in complete resolution of symptoms and signs. PMID- 20587266 TI - Posttraumatic intradural internal carotid artery-cavernous sinus fistula associated with ipsilateral carotid dissection. Transarterial embolization with detachable coils. AB - SUMMARY: We describe a relatively unusual case of traumatic direct carotid cavernous fistula in association with a giant intradural venous pouch and ipsilateral carotid dissection, related to carotid artery fistula located in the supraclinoid segment just below the origin of posterior communicating artery. Endovascular therapy could be accomplished by use of detachable coils transarterially. Awareness of an unusual intradural origin of a carotid-cavernous sinus fistula and the possibility of an embolization should be kept in mind. PMID- 20587267 TI - Cavernous sinus dural fistula treated by transvenous facial vein approach. AB - SUMMARY: We report on the endovascular treatment of the spontaneous indirect dural carotid cavernous sinus type D fistula in a 60-year-old woman, in whom ipsilateral facial, angular and superior ophthalmic veins catheterization was performed to get access to the fistula site for embolization treatment. Approach via the facial vein is helpful after inferior petrosal sinus treatment failure. Although this technique requires caution in the angular vein region it allows a safe and effective treatment of these lesions. 3D rotational digital angiography can obtain more information of the angioarchitecture of the cavernous plexus and venous outflow for the catheter navigation. PMID- 20587268 TI - Endovascular coiling of multiple (more than four) intracranial aneurysms. Case report. AB - SUMMARY: The incidence of multiple intracranial aneurysms has been reported from 5% to 35%. But over four multiple aneurysms are extremely rare. Sometimes it is very difficult to draw a clear line between ruptured ones and unruptured others especially in multiple aneurysm cases with even distribution of subarachnoid haemorrhage on basal cistern. We present two cases of multiple aneurysms, more than four, which were successfully treated by endovascular coiling at the same time. Our experience suggests an endovascular procedure would be the gold standard of treatment for ruptured multiple intracranial aneurysms. PMID- 20587269 TI - Newly developed embolic material mesosphere and titanium. Experimental and clinical studies. PMID- 20587270 TI - Cerebral diagnostic and therapeutic angiography for neonatal arteriovenous fistulas. AB - SUMMARY: Cerebral diagnostic and therapeutic angiography for neonatal arteriovenous fistulas is reported. Three neonatal boys with vein of Galen aneurysmal malformation (1 patient) and dural arteriovenous fistulas (2 patients) presented severe congestive heart failure soon after birth, and were treated by transarterial and/or transvenous embolization using various access routes. In the neonatal period, umbilical approach and direct cervical approach provide unique access routes in addition to the usual transfemoral route. Characteristics of neonatal angiography are discussed. PMID- 20587271 TI - Selective transvenous embolization for dural arteriovenous fistulas with the aid of superselective venograms of fistulous drainages and involved sinuses. AB - SUMMARY: For the treatment of transvenous embolization (TVE) of dural arteriovenous fistulas (DAVFs) the sites of arteriovenous shunts, fistulous drainage, and the pathological changes inside the affected sinuses were explored in detail by means of preoperative arteriograms, superselective arteriograms, and superselective venograms. Out of 42 adult patients with DAVFs involving a total of 63 sinuses, three distinctive findings were identified as essential for indication of selective TVE for DAVFs. The first is extra-sinus fistulous drainage, which is embolizable fistulous drainage, remote from the major dural sinus, that flows into the sinus lumen. The second is intramural fistulous drainage, which is embolizable fistulous drainage located within the dural leafs of the involved sinus and separate from the major sinus lumen. The third consists of several lumens inside the affected sinuses, which suggests a variety of histological changes in the developmental process of sinus thrombosis and DAVFs. The extra-sinus drainage was occluded in three torcular heroplili fistulas and three transverse sinus fistulas. The intramural fistulous drainage was eliminated in three superior sagittal sinus fistulas. Several lumens inside the affected sinuses were encountered in 17 posterior fossa fistulas (68%) and 10 cavernous sinus fistulas (34%). These distinctive findings were recognized in 52% of the DAVFs. Out of various modalities for treatment of DAVFs, TVE has been the method of choice for the treatment of diffuse DAVFs. The TVE of DAVFs do not correspond to simple sinus occlusion, but imply selective occlusion of fistulous drainages and sinus lumens. The recognition of these three distinctive types of fistulous drainages have clinical impact in that it helps to completely occlude all the fistulous components of fistulas as well as preserve or restore the normal venous outflow through the involved sinus. PMID- 20587272 TI - Endovascular Treatment of Cerebral Aneurysm with Coils and Onyx. in-vivo experiment. AB - SUMMARY: We investigated endovascular treatment of cerebral aneurysm by coil and Onyx in vivo experiment in order to promote the advantages of coil embolization,. The aim of this study was to clarify the advantages and problems of coil and Onyx embolization and to evaluate its potentials for application in clinical medicine. We set experimental aneurysms made of external jugular vein to bilateral carotid arteries of 10 Beagle dogs and embolized aneurysm with coils and Onyx.Two months later, the dogs were sacrificed and took out the experimental aneurysms and examined them histologically. We have experienced Onyx migration into the vessel at the beginning of our experiment. Technical problems were as follows; Onyx was not easily visible on DSA monitor particularly in tight coil packing. Catheter tip was often stuck to the Onyx in the aneurysm. Protect balloon could not completely protect the Onyx leakage into the vessel. Microscopic examinations were as follows; The aneurysm was filled with Onyx, coils, and inflammatory reactants. The orifice of the aneurysm was packed with augmented fibrous tissue. 1. This method increased contact between the aneurysm wall and coils. 2. Onyx filled the intra-aneurismal space more tightly. 3. Coils prevented Onyx from flowing out into the vessel. 4. In Onyx, intimal layer was more rapidly formed at the neck of the aneurysm than coils only. 5. The most important problems during Onyx embolization is how to prevent Onyx migration into the vessel. We should like to propose the guideline for Onyx embolization. PMID- 20587273 TI - The study on the patency of the perforating arteries after stent placement in atherosclerosis induced rabbits. AB - SUMMARY: The number of successful case reports with percutaneous transluminal angioplasty (PTA) / stenting for intracranial atherosclerotic stenoses is recently increasing with the advent of flexible coronary stents. However, it is not well known whether the perforating artery is occluded or not after stent placement in the atherosclerotic stenotic vessels. We investigated this issue using five New Zealand white rabbits. We deployed stainless steel stents in the atherosclerosis-induced abdominal aorta across the lumbar artery in which the diameters of the abdominal arteries were similar to those of human intracranial arteries. We evaluated the patency of lumbar artery by angiography and scanning electron microscopy three months after stent placement. The lumbar arteries were patent in four out of five rabbits. However, SEM findings demonstrated stent struts were covered with thick neointima and the ostia between stent struts were partially occluded. It is possible that stent placement in the atherosclerotic arteries can cause the obliteration of the perforating arteries. PMID- 20587274 TI - Strategy for Prevention of Restenosis after PTA. Clinical and Basic Approaches. AB - SUMMARY: Percutaneous transluminal angioplasty (PTA) has been a useful therapy to treat stenosis of cervical internal carotid artery (ICA) or vertebral artery (VA). Here we show that our clinical results regarding preventive effect of stenting on restenosis after PTA in the ICA and VA origin. We also show our experimental studies with gene transfer techniques aiming reduction of restenosis after balloon-injury in rat carotid artery. It has been reported that drug eluting stent inhibits restenosis after coronary angioplasty. Further understanding of the mechanism of restenosis and application of these new modalities may lead to better clinical results in angioplasty of the craniocervical arteries. PMID- 20587275 TI - Development of an intravascular laser treatment with an infrared free electron laser. Selective removal of cholesterol ester in carotid atheromatous plaques. AB - SUMMARY: We have studied to develop an intravascular device with an infrared free electron laser (FEL) to treat occlusive carotid atherosclerotic lesions. In this study, we irradiated the FEL with a wavelength of 5.75 mum on surgical specimens of human atheromatous carotid plaques. After the irradiation on a cholesterol ester-accumulated portion of the carotid plaques under proper conditions, a microscope transmission FTIR (Fourier Transform Infrared) spectroscopy showed that the peak of a tissue infrared absorption spectrum corresponding to the molecular vibration of cholesterol ester (5.75 mum) disappeared.Tissue damages associated with the irradiation were not histologically noted. This study demonstrated that irradiation of FEL can selectively remove cholesterol ester from the human atheromatous carotid plaques. PMID- 20587276 TI - Reperfusion Therapy for Acute Middle Cerebral Artery Trunk Occlusion. Direct Percutaneous Transluminal Angioplasty Versus Intra-arterial Thrombolysis. AB - SUMMARY: The purpose of this study was to test the hypothesis that direct percutaneous transluminal angioplasty (PTA) might reduce the incidence of haemorrhagic complications and might improve recanalization rate and clinical outcome as compared with intra-arterial (IA) thrombolysis in patients with acute middle cerebral artery (MCA) trunk occlusion. A total of 70 patients with acute MCA trunk occlusion were treated with IA reperfusion therapy. Thirty-six patients were treated with IA thrombolysis alone. In the other 34 patients, direct PTA was selected as the first choice of the treatment and subsequent thrombolysis was added if necessary for distal embolization. The modified Rankin scale (mRS) was used to assess clinical outcome at 90 days. As compared with IA thrombolysis, direct PTA provided significant increase in the rates of partial or complete recanalization (63.9 vs 91.2%, p < 0.01) and decrease in the incidence of large parenchymal hematoma with neurological deterioration (19.4% vs 2.9%, p=0.03). Despite such favorable effects, direct PTA did not improve the rate of a favorable outcome (mRS score 0 or 1, 41.7% for the IA thrombolysis group vs 52.9% for the PTA group, p=0.48). However, outcome classified in terms of independence (mRS score 65years, many frail. The purpose of this study was to determine if frailty explains variability in health related quality of life (HRQOL) in older adults with HF over and above known correlates. METHODS: A frailty index score was developed by weighting age, number of comorbid conditions, and symptom severity. A multivariate hierarchical regression analysis of known predictors of HRQOLgender, income, ethnicity, health perception, NYHA class - were entered first and then the frailty index was entered and regressed on HRQOL in 2 unique samples. RESULTS: When known predictors were tested on a sample they explained 11% (p 0.14) of the variance in HRQOL; when the frailty index score was added 24% (p 0.001) was explained. When the index was validated in a second sample, known predictors explained 15% (p 0.04) of the variance; with the frailty index score 40% (p 0.000) was explained. CONCLUSION: Frailty explains significant amounts of variance in HRQOL in HF. Treating comorbid conditions and controlling symptoms may improve HRQOL in HF patients. These findings support the need for further research into the impact of frailty on HRQOL in HF patients. PMID- 20587373 TI - Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs. AB - Two dogs were diagnosed with iatrogenic thyrotoxicosis (1 definitive, 1 presumptive). Both showed physical examination findings of agitation, tachypnea, and tachycardia. Sinus tachycardia with supraventricular ectopy was diagnosed in one case, and syncope and atrial flutter was present in the other. Both dogs had concurrent cardiac disease that might have contributed to the severity of their clinical signs. Excessive thyroid hormone supplementation in humans causes supraventricular arrhythmias including sinus tachycardia, supraventricular tachycardia, atrial fibrillation, and atrial flutter. Clinical signs and rhythm abnormalities resolved in both dogs with resolution of the thyrotoxicosis. PMID- 20587374 TI - The pancreatic stump after pancreatoduodenectomy: the "Achille's heel" revisited... AB - Pancreatic fistula, the most dreaded complication of pancreatoduodenectomy occurs with an incidence ranging from 4-30% in literature reports; the incidence varies considerably according to the definition of fistula used. This literature review describes various methods proposed over the last decade to decrease the incidence and severity of pancreatic fistula including techniques of pancreatico-jejunal and pancreatico-gastric anastomoses, deliberate avoidance of pancreatico-enteric anastomosis, and the prophylactic role of somatostatin analogues. PMID- 20587375 TI - Sexual and urinary dysfunction after proctectomy for rectal cancer. AB - Sexual and urinary dysfunction occur frequently after rectal surgery. Total mesorectal excision (TME) is currently the optimal technique for resection of rectal cancer, providing superior carcinological and functional outcomes. Age, pre-operative radiation therapy, abdominoperineal resection, and surgery which fails to respect the "sacred planes" of TME are the four major risk factors for post-operative sexual and urinary sequelae. In the era of TME, postoperative sexual dysfunction ranges from 10-35%, depending on the scores used to assess it, while urinary sequelae have decreased to less than 5%. The place of laparoscopic surgery remains to be defined, particularly with respect to these complications. It is essential to inform the patient pre-operatively about the possibility of such disorders not only for patient informed consent but also to help with correct post-operative management of the problem. Management is multifaceted, and includes psychological, pharmacological, and sometimes surgical therapy. PMID- 20587376 TI - Reimplantation of the superior mesenteric artery. PMID- 20587377 TI - Laparoscopic right colectomy. PMID- 20587378 TI - New clinical features of thyroid cancer in eastern China. AB - OBJECTIVE: Analyze recent clinical features of thyroid cancer in eastern China. METHODS: Investigation and comparison of clinical data of thyroid cancer patients from 1996 to 2006 from the Department of Head and Neck Surgery in the Cancer Hospital of Fudan University, Shanghai, China. RESULTS: The number of patients with thyroid cancer rose from 148 in the year 1996 to 572 in the year 2006, a 3.9 fold increase. Routine ultrasound survey during physical examination revealed four cases (2.7%) in 1996 and 285 cases (49.8%) in 2006. The sensitivity of the ultrasound survey in thyroid cancer diagnosis was 86.66% in 1996 and 88.20% in 2006 (P>0.05). Papillary carcinoma was most prevalent (87.8% in 1996 and 92.8% in 2006). An increasing proportion of small tumors was found. The incidence of microcarcinoma was 35.7% in 2006 in contrast with 20.3% in 1996 (P<0.01). Moreover, tumors with diameter from 1 to 2 cm were found in 38.5% patients in 2006 as opposed to 27.0% in 1996 (P<0.01). Extrathyroid extension was reported in 46 (31.1%) patients in 1996, but only in 39 (6.8%) in 2006 (P<0.01). Central cervical lymph node metastases were found in 98 (66.2%) patients in 1996, contrasting with 301 (52.6%) in 2006 (P<0.05). Thirty-seven (25.0%) patients had lateral cervical lymph node metastasis in 1996 compared with 117 (20.5%) in 2006 (P>0.05). Last, the proportion of stage I cancers in 2006 was higher than that in 1996. CONCLUSION: With the increasing incidence of thyroid cancer, cancer was discovered at an earlier stage. This is due to new clinical features of thyroid cancer, such as the decrease in tumor diameter, the lower rate of extrathyroid extension and of cervical lymph node metastasis. Routine ultrasound survey during physical examination has become the most common way to detect thyroid cancer. Increasing usage of diagnostic scrutiny, including the ultrasound survey, has most likely contributed to the increased incidence through detection of small thyroid cancers. Increased use of ultrasound to screen thyroid cancer in early stages should lead to better therapeutic outcome. PMID- 20587379 TI - Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report. AB - We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. PMID- 20587380 TI - Do the health benefits of cycling outweigh the risks? AB - BACKGROUND: Although from a societal point of view a modal shift from car to bicycle may have beneficial health effects due to decreased air pollution emissions, decreased greenhouse gas emissions, and increased levels of physical activity, shifts in individual adverse health effects such as higher exposure to air pollution and risk of a traffic accident may prevail. OBJECTIVE: We describe whether the health benefits from the increased physical activity of a modal shift for urban commutes outweigh the health risks. DATA SOURCES AND EXTRACTION: We have summarized the literature for air pollution, traffic accidents, and physical activity using systematic reviews supplemented with recent key studies. DATA SYNTHESIS: We quantified the impact on all-cause mortality when 500,000 people would make a transition from car to bicycle for short trips on a daily basis in the Netherlands. We have expressed mortality impacts in life-years gained or lost, using life table calculations. For individuals who shift from car to bicycle, we estimated that beneficial effects of increased physical activity are substantially larger (3-14 months gained) than the potential mortality effect of increased inhaled air pollution doses (0.8-40 days lost) and the increase in traffic accidents (5-9 days lost). Societal benefits are even larger because of a modest reduction in air pollution and greenhouse gas emissions and traffic accidents. CONCLUSIONS: On average, the estimated health benefits of cycling were substantially larger than the risks relative to car driving for individuals shifting their mode of transport. PMID- 20587381 TI - Interference among viruses circulating and administered in Hungary from 1931 to 2008. AB - Viral interference was discovered about 60 years ago. Molecular epidemiology revealed that this phenomenon possesses important biological implications, it can reduce the epidemic spread of certain viruses from time to time (influenza and enteroviruses) and the efficiency of live vaccination can be impaired, too. Phenomena observed during the last 80 years in Hungary are analyzed. It is suggested to concentrate the distribution of MMR vaccines to seasons of limited influenza and enterovirus circulation. Interference seems to impair the progress of wild poliovirus eradication in the endemic tropical countries. It is recommended to enhance enterovirus surveillance in the region of European countries, since the exchange of the oral poliovirus vaccine to the enhanced inactivated polio vaccine might result in enhanced circulation of non-polio enteroviruses leading to the increase in the number of type I (juvenile) diabetes patients. PMID- 20587382 TI - Rapid identification of Iranian Acinetobacter baumannii strains by single PCR assay using BLA oxa-51 -like carbapenemase and evaluation of the antimicrobial resistance profiles of the isolates. AB - The rapid identification of relevant bacterial pathogens is of utmost importance in clinical settings. The aim of this study was to test a rapid identification technique for A. baumannii strains from Tehran Hospitals and to determine the antibiotic resistance profiles of the isolates. A hundred strains of Acinetobacter spp. grown from clinical specimens were identified as A. baumannii by conventional methods. Using PCR a bla OXA-51 -like gene was detected in all A. baumannii isolates but not in other species of acinetobacter. More than half of the isolates proved resistant to a variety of antibiotics by the disk diffusion technique. The rate of resistance to gentamicin, imipenem, ampicillin-sulbactam and amikacin was determined to be 45%, 53%, 62% and 62%, respectively. Moreover, most isolates (more than 90%) showed resistance to cephalosporins. This study shows that the demonstration of the bla OXA-51-like gene is a reliable and rapid way for the presumptive identification of A. baumannii and reveals that the rate of antibiotic resistance is high in Iranian A. baumannii isolates to a variety of antibiotics. PMID- 20587383 TI - Inhibition of growth and caseinase production of Pseudomonas aeruginosa and Escherichia coli 28 by combination of low pH and NaCl, potassium sorbate or Thymus vulgaris extract. AB - Previous studies reported that, at neutral pH (e.g. 7.4), many preservatives do not have antimicrobial effect against Pseudomonas aeruginosa and some strains of E. coli . This study investigated the effect of combination of low pH and some preservatives (e.g. sodium chloride, potassium sorbate or Thymus vulgaris extract) on the growth and caseinase production of Pseudomonas aeruginosa and E. coli at 31 degrees C and 7 degrees C. At 31 degrees C, although growth of the strains was not affected by low pH (5.7) alone, caseinase production by both strains was decreased. A combination of low pH and NaCl, potassium sorbate or thyme extract significantly reduced (p < 0.05) growth and caseinase production by E. coli 28 at 31 degrees C. For P. aeruginosa , addition of NaCl or thyme extract to nutrient broth (low pH) did not affect the growth but reduced caseinase production of the tested strain. Combination of low temperature (7 degrees C) and growth in nutrient broth (low pH) plus sodium chloride or nutrient broth (low pH) plus potassium sorbate was the most effective treatment in reducing or inhibiting growth and caseinase production of the tested strains. PMID- 20587384 TI - Investigation of mineral water springs of Miercurea Ciuc (Csikszereda) region (Romania) with cultivation-dependent microbiological methods. AB - Water samples of ten mineral water springs at Miercurea Ciuc (Csikszereda) region (Romania) were examined during 2005-2006 using cultivation-dependent microbiological methods. The results of standard hygienic bacteriological tests showed that the Hargita Spring had perfect and five other springs had microbiologically acceptable water quality (Zsogod-, Nagy-borviz-, Taploca-, Szentegyhaza- and Lobogo springs). The water of Borsaros Spring was exceptionable (high germ count, presence of Enterococcus spp.).Both standard bacteriological and molecular microbiological methods indicated that the microbiological water quality of the Szeltersz-, Nadasszek- and Delo springs was not acceptable. Bad water quality resulted from inadequate spring catchment and hygiene (low yield, lack of runoff, negligent usage of the springs, horse manure around the spring).The 16S rRNA gene-based identification of strains isolated on standard meat-peptone medium resulted in the detection of typical aquatic organisms such as Shewanella baltica, Aeromonas spp., Pseudomonas veronii, Psychrobacter sp,. Acinetobacter spp. and allochthonous microbes, like Nocardia, Streptomyces, Bacillus, Microbacterium , and Arthrobacter strains indicating the impact of soil. Other allochthonous microbes, such as Staphylococcus spp., Micrococcus sp., Lactococcus sp., Clostridium butyricum, Yersinia spp., Aerococcus sp., may have originated from animal/human sources. PMID- 20587385 TI - Pattern of matrix metalloproteinases-9, P53 and BCL-2 proteins in Egyptian patients with pulmonary Mycobacterium tuberculosis. AB - Matrix metalloproteinases (MMPs) constitute a large family of enzymes that degrade extracellular matrix proteins (ECM). MMPs are implicated in different pathological conditions such as cancer. Bcl-2 and P53 are key controllers of programmed cell death (PCD) or apoptosis. The aim of the present study was to determine the MMP-9, P53 and Bcl-2 levels in Egyptian patients with Mycobacterium tuberculosis (MTB) (Group I) compared with healthy control individuals (Group II). The concentrations of serum MMP-9 were determined quantitatively using enzyme immunoassay (EIA). P53 and Bcl-2 levels were assayed by flow cytometric analysis using specific monoclones. MMP-9 level was significantly higher in MTB patients compared with healthy control. Similarly, P53 and Bcl-2 levels were increased in MTB patients compared with healthy ones. These data reflect the alteration of MMP-9 level during the course of MTB infection, accompanied with apparent dysregulation of cellular apoptosis as indicated by P53 and Bcl-2 over expression. PMID- 20587386 TI - Generation of mutant of Rhodococcus rhodochrous PA-34 through chemical mutagenesis for hyperproduction of nitrile hydratase. AB - Rhodococcus rhodochrous PA-34 has been reported to produce nitrile hydratase enzyme that converts 3-cyanopyridine to nicotinamide. A mutant of R. rhodochrous PA-34 was generated through chemical mutagenesis using N-methyl-N-nitro-N nitrosoguanidine (MNNG) that exhibited 2 times higher nitrile hydratase activity as compared to wild strain. The reaction conditions using resting cells of this mutant strain for the conversion of nicotinamide were optimized. Under the optimized reaction conditions the mutant strain exhibited maximum nitrile hydratase activity [7.8 U/mgdcm (milligram dry cell mass)] at 55 degrees C in 0.3 M potassium phosphate buffer (pH 5.5). PMID- 20587387 TI - Induced expression of lectin-like oxidized ldl receptor-1 in vascular smooth muscle cells following Chlamydia pneumoniae infection and its down-regulation by fluvastatin. AB - Microorganisms such as Chlamydia pneumoniae have been shown to infect vascular cells and are believed to contribute to vascular inflammation and atherosclerotic plaque development. Plasma levels of oxidized low density lipoprotein (oxLDL) have received considerable attention as potential predictors of prognosis in atherosclerotic diseases. Lectin-like oxidized LDL receptor-1 (LOX-1) is one of the major receptors for oxidized LDL. It was investigated whether C. pneumoniae infection can stimulate expression of LOX-1 in vascular smooth muscle cells. Expression of LOX-1 in VSMC was measured by RT-PCR and immunoblotting following C. pneumoniae infection. To examine the pharmacological effect of a HMG-CoA reductase inhibitor on LOX-1 expression, cells were co-incubated with fluvastatin immediately after infection. A dose and time dependent expression of LOX-1mRNA and protein was found in C. pneumoniae infected SMC. After heat and UV light treatment of the chlamydial inoculum the level of LOX-1 was reduced to that of mock-infected cultures. Furthermore, treatment of infected cells with fluvastatin decreased LOX-1 expression to baseline levels. The up-regulation of LOX-1 induced by C. pneumoniae could lead to continued lipid accumulation in atherosclerotic lesions. Together with the widespread expression of LOX-1, this might contribute to the epidemiologic link between C. pneumoniae infection and atherosclerosis. The effect of lowering the LOX-1 expression by fluvastatin may provide a pharmacological option of limiting oxLDL uptake via its scavenger receptor. PMID- 20587388 TI - Protective effects of selenium, calcium, and magnesium against arsenic-induced oxidative stress in male rats. AB - Inorganic arsenic is a potent carcinogen and environmental pollutant. More than one hundred million people are reported to be exposed to elevated concentrations of arsenic mainly via drinking water. Essential trace elements can affect toxicity of metals by interacting with metals at the primary site of action and can also modify the body's response to toxic metals by altering their metabolism and transport. This study investigates the effects of concomitant administration of selenium, magnesium, and calcium with arsenic on blood biochemistry and oxidative stress. Selenium was the most effective in reducing arsenic-induced inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity and liver oxidative stress. Calcium and magnesium also showed favourable effects on haematological and other biochemical parameters. Because selenium was the most effective, it should be added to chelation therapy to achieve the best protective effects against arsenic poisoning in humans. PMID- 20587389 TI - Endotoxin exposure assessment in wood-processing industry: airborne versus settled dust levels. AB - Wood processing is usually performed in environments with large amounts of endotoxin-rich bioaerosols that are associated with a variety of health effects. The aim of this preliminary study was to assess the relation between endotoxin levels in settled and airborne dust in wood-processing industry. Ten pairs of airborne and settled dust samples were collected in a sawmill and parquet manufacture of two wood-processing plants in Croatia. Endotoxin was assayed with a chromogenic end-point LAL (Limulus amebocyte lysate) method. The results showed that endotoxin levels in airborne respirable dust were above the proposed occupational exposure limit of 125 EU m(-3) and could be considered hazardous for the respiratory system. In settled dust they ranged between 229.7 EU mg(-1) and 604.3 EU mg(-1) and in airborne dust between 166.8 EU mg(-1) and 671.6 EU m(-3), but there was no significant correlation between them (Spearman's rho=0.358, P=0.310). This study points to sawmill settled dust as endotoxin reservoir and suggests that it may add to already high exposure to airborne endotoxins associated with wood processing. Investigations of the relation between settled and airborne endotoxin levels should be continued to better understand the sources and sites of endotoxin contamination in wood-processing industry. PMID- 20587390 TI - Determination of Aspergillus fumigatus allergen 1 in poultry farms using the enzyme immunoassay. AB - Poultry farms contain high levels of allergenic fungi, and Aspergillus spp. is the most common genus of moulds. Aspergillus fumigatus antigens are responsible for the development of several respiratory diseases including asthma. The aim of this study was to measure the mass fraction of Asp f 1, a major allergen of Asperillus fumigatus in 37 indoor dust samples collected from four poultry farms in a rural area of the Zagreb County (Croatia) using the enzyme-linked immunosorbent assay. More than 62 % of dust samples had detectable Asp f 1 levels (limit of detection 3.6 ng g(-1)). The overall mean Asp f 1 level was 17.9 ng g( 1) [range (3.8 to 72.4) ng g(-1)]. Satisfactory results were obtained for analytical within-run imprecision (6.7 %), between-run imprecision (10.5 %), and accuracy (91 % to 115 %). Microclimate parameters (air temperature, relative humidity, and velocity) were within the recommended ranges in all poultry farms. This study has shown that Asp f 1 settles on dust at poultry farms and that occupational exposure to this allergen deserves monitoring in livestock buildings. PMID- 20587391 TI - Presence of ecotoxicologically relevant Pgp and MRP transcripts and proteins in Cyprinid fish. AB - One of the most intriguing defence strategies which aquatic organisms developed through evolution is multixenobiotic resistance (MXR). The key mediators of MXR activity are ATP-binding cassette (ABC) transport proteins. They provide resistance of aquatic organisms by binding xenobiotics and extruding them from cells in an energy-dependent manner. Since Cyprinid fish species are common target in freshwater biomonitoring programs, we have studied the presence of two main MDR/MXR efflux transporters P-glycoprotein (Pgp, Abcb1) and MRP-like protein(s) (Abcc) in the liver of five Cyprinid species: common carp, European chub, sneep, barbel, and silver prussian carp. Their presence was evaluated on the mRNA and protein level. Various pairs of primers were designed to clone homologous fragments of MXR-related genes. At the protein level, we used Western blotting with specific monoclonal antibodies against human Pgp (Abcb1, Ab C219), MRP1 (Abcc1; Ab MRPm6) or MRP2 (Abcc2; Ab M2I-4). Transcripts of both key types of MXR transporters were identified in all species examined and here we provide the phylogenetic analysis of new partial sequences. Immunochemical determinations with mammalian antibodies failed to identify the presence of MRP(s), but Pgp expression was found in all five Cyprinid species. These results support that MXR is a defence system mediated by both Pgp and MRP types of ABC transport proteins. PMID- 20587392 TI - Effect of 1,6-hexamethylene diisocyanate exposure on peak flowmetry in automobile paint shop workers in Iran. AB - The aim of this study was to investigate the effects of occupational exposure to 1,6-hexamethylene diisocyanate (HDI) on peak flowmetry in automobile body paint shop workers in Iran. We studied a population of 43 car painters exposed to HDI at their workplaces. Peak expiratory flow was tested for one working week, from the start to the end of each shift. Air was sampled and HDI analysed in parallel, according to the OSHA 42 method. Daily and weekly HDI exposure averages were (0.42+/-0.1) mg m(-3) and (0.13+/-0.05) mg m(-3), respectively. On painting days, 72 % of workers showed more than a 10 % variation in peak expiratory flow. Inhalation exposure exceeded the threshold limit value (TLV) ten times over. This strongly suggests that HDI affected the peak flowmetry in the studied workers. PMID- 20587393 TI - Growth inhibition of Aspergillus ochraceus ZMPBF 318 and Penicillium expansum ZMPBF 565 by four essential oils. AB - Fungi produce a large variety of extracellular proteins, organic acids, and other metabolites and can adapt to several environmental conditions. Mycotoxin producing moulds of the genera Aspergillus and Penicillium are common food contaminants. One of the natural ways to protect food from mould contamination is to use essential oils. In this study, we evaluated the effect of essential oils of cinnamon, lavender, rosemary, and sage at 1 % (v/v) concentration in yeast media inoculated with spores (final concentration 106 mL-1 media) of Aspergillus ochraceus ZMPBF 318 and Penicillium expansum ZMPBF 565, alone or in combination, on fungal biomass. Cinnamon showed the best inhibitory effect (100 %). Lavender oil best inhibited the growth of Aspergillus ochraceus (nearly 100 %), and was less successful with Penicillium expansum (having dropped to 57 % on day 28). With cultivation time the inhibitory effect of sage and rosemary oil grew for Aspergillus ochraceus and dropped for Penicillium expansum.These results suggest that fungi can be controlled with essential oils, especially with cinnamon oil. PMID- 20587394 TI - Knowledge of HCV infection among nursing students of the Medical College of Bitola. AB - Healthcare workers are at risk of occupationally-acquired viral infections such as human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). HCV is parenterally transmitted and has been found in every part of the world. This cross-sectional study was conducted to establish the awareness and attitude about HCV infections among 210 full-time and part-time nursing students of the Medical College in Bitola, Macedonia from May to June 2009. For this purpose we used a self-administered questionnaire which consisted of three parts. The first included demographic data, the second included questions about causes of infection, mode of transmission, symptoms, acute and chronic hepatitis, and prevention, and the third questions about students' attitude toward patients with suspect or confirmed HCV infection. Full-time students showed higher HCV awareness (84 %) than part-time students (69 %). 58 % of the full-time and 79 % of the part-time students said they would not avoid professional contact with suspect or HCV infected patients. Our study has shown that even though both groups of students have a sufficient knowledge about HCV to face future challenges, they need further education on the subject. Practical recommendations would help to reduce stigmatising behaviour still further. PMID- 20587395 TI - Prevalence of smoking and other smoking-related behaviours among students aged 13 to 15 years in Montenegro: results from the Global Youth Tobacco Survey of 2008. AB - The Global Youth Tobacco Survey (GYTS) is an international study that provides data on youth tobacco use for development of tobacco control programs. It is a school-based survey that uses a standardised methodology for sampling, core questionnaire items, training protocol, field procedures, and data management. This article reports the findings from a GYTS conducted in Montenegro in 2008, which included 5723 adolescents. More than 30 % of students aged 13 to 15 tried smoking, 5.1 % smoked cigarettes, and 3.6 % of students used tobacco products other than cigarettes. Four in 10 ever smokers started to smoke before the age of 10. More than half the students reported secondary smoke exposure at home. Almost all (96.5 %) current smokers bought cigarettes in a store. Two in 10 students owned an artifact with a cigarette or tobacco brand logo on it. The GYTS study has shown that there is an urgent need to introduce effective child-oriented smoking prevention programmes in early elementary school classes. These should be accompanied by public awareness campaigns on smoke-free homes. PMID- 20587396 TI - [Hypersensitivity to pollen of Olea europea in patients with pollen allergy in Zadar County, Croatia]. AB - Olive pollen is one of the most common respiratory allergens in the Mediterranean countries. The aim of this study was to establish the frequency of hypersensitivity to the pollen of Olea europea in pollen allergic patients in the County of Zadar. The study included 671 patients with pollen allergy; 61 % were male and 39 % female. 53.5 % were children aged from 4 to 14 years and 46.5 % adolescents and adults from 15 to 59 years. We took their case history, clinically examined them, and tested using the skin prick test and enzymo immunologic UniCAP test for specific IgE antibodies. For statistical analysis we used the chi-square test. Hypersensitivity to Olea europea pollen was confirmed in 8.8 % patients with pollen allergy. Among them, the most prevalent symptom was rhinitis (58 %). Most hypersensitive patients were urban residents. Only 3 % patients lived on an island. Judging by available data, our findings show the lowest hypersensitivity to olive pollen in the Mediterranean. A comparison with our two earlier studies did not show any fluctuation in this kind of hypersensitivity. PMID- 20587397 TI - [Normal and cut-off values of the cytokinesis-block micronucleus assay on peripheral blood lymphocytes in the Croatian general population]. AB - The cytokinesis-block micronucleus (CBMN) assay on peripheral blood lymphocytes is one of the most important methods employed in cytogenetic biomonitoring. For the purposes of biological dosimetry, it is important to know the spontaneous frequency of a biomarker and its normal values in general population. These values are used for population databases, which should be updated regularly. In this study, MN levels were investigated in cytokinesis-blocked lymphocytes of 200 healthy male and female blood donors selected at random from the general population of Croatia. The aim was to assess the variability and determine possible influences of external and/or internal factors on the background levels of MN and to establish the cut-off value for the CBMN assay. The background frequency of MN was (6.90+/-3.32) MN (median 7 MN) and the range was 0 to 18 MN per 1000 binuclear lymphocytes. The cut-off value, which corresponds to 95th percentile of the distribution of 200 individual values, was 12.5 MN. Spontaneous formation of MN was influenced by sex, age, and smoking. Women had higher MN levels than men. However, only age and smoking significantly increased the values of all parameters evaluated by the CBMN assay. Since the existing literature data on smoking-related formation of MN are contradictory, we will continue these investigations to resolve how the number of cigarettes smoked per day and the duration of smoking in years influence the results of the CBMN assay. Our results are consistent with the background MN frequencies reported by other cytogenetic laboratories worldwide. Normal and cut-off values estimated in this study will be used to update the current general population data and as reference for occupationally or accidental exposure. PMID- 20587398 TI - Elements of natural radioactive decay series in Iranian drinking water and cigarettes. AB - The uranium (238U) decay series provides the most important isotopes of elements radium (226Ra), radon (222Rn), and polonium (210Po) with half-lives of about 1600 years, 3.8 days, and 140 days, respectively. Although the chemical structure of radium is very similar to calcium, the fact that it produces a radioactive gas (radon) complicates its handling in the laboratory and natural environment. In this study, we used the average concentrations of naturally occurring radionuclide 226Ra in drinking water at different parts of Iran to estimate the annual effective dose. In the other part of the study, we measured the concentrations of 210Po in Iranian cigarettes to estimate the internal intake of this radionuclide and its concentration in the lung tissues of smokers. The results indicate that the average concentration of 226Ra in Iranian drinking water was below the 100 mBq L(-1) recommended by the World Health Organization while the average concentration of 210Po and 210Pb in Iranian cigarettes was relatively high in comparison with other cigarettes found on the market. PMID- 20587399 TI - Extreme hyperkalaemia caused by concomitant use of a NSAID and an ace inhibitor in an elderly patient. AB - Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function. PMID- 20587400 TI - [Toxicological effects of weapons of mass destruction and noxious agents in modern warfare and terrorism]. AB - Weapons of mass destruction (WMD) best portray the twisted use of technological achievements against the human species. Despite arm control efforts, WMD threat continues to exist and even proliferate. This in turn calls for improvement in defensive measures against this threat. The modern soldier is exposed to a number of chemical, biological, and radiological agents in military and peace operations, while civilians are mainly exposed to terrorist attacks. Regardless of origin or mode of action, WMDs and other noxious agents aim for the same - to make an organism dysfunctional. Because their effects are often delayed, these agents are hard to spot on time and treat. This review presents a biomedical aspect of agents used in warfare and terrorism, including polonium-210, depleted uranium, salmonella, anthrax, genetically modified bacteria, cobweb-like polymer fibre, sarin, and mustard gas. PMID- 20587401 TI - [Genome instability and bleomycin sensitivity test]. AB - Estimation of individual susceptibility to mutagens is often a part of epidemiological studies monitoring the appearance of malignant disease in different populations. Genome exposure to mutagens can lead to DNA damage. The rate of damage depends on individual differences in response, which are usually associated with differences in DNA repair capacity. Cytogenetic studies have shown that the genome of tumour cells is less stable than normal cells and therefore accumulates more damage. Tumour patients show a higher frequency of chromatid and chromosomal aberrations and a predisposition to certain types of tumours. One of the common biomarkers used in monitoring tumour appearance and changed response to DNA damage is the bleomycin test. In its active form, bleomycin (glycopeptid) is a radiomimetic cytostatic that can damage the DNA molecule and cause multiple single and double strands. The bleomycin test is simple and inexpensive, and is based on scoring chromatid breaks in lymphocytes in vitro exposed to bleomycin during the late G2 phase of the cell cycle. This review looks into different factors that may affect test results and discusses its wide implementation in studies of genome instability usually caused by a combination of factors. PMID- 20587403 TI - Novel treatment approaches for triple-negative breast cancer. AB - Triple-negative breast cancers share an aggressive biology, marked by increased recurrence risk and poorer survival compared with hormone receptor-positive subtypes. Few therapeutic trials have specifically focused on triple-negative breast cancer, and the treatment of patients with early-stage triple-negative breast cancer has changed little in the past decade. Over this time, however, attention has shifted to treatment approaches based on molecular subtypes of breast cancer, and investigation into the mechanistic underpinnings of these distinct subtypes has exploded. Converging preclinical rationales combined with early provocative clinical efficacy has focused recent attention on strategies targeting DNA repair defects for the treatment of patients with triple-negative and BRCA mutation-associated breast cancers. These developments are very promising and suggest that major advances in the targeted treatment of patients with triple-negative breast cancer are in sight. This review provides an overview of the clinical features of triple-negative breast cancer and current treatment strategies in the adjuvant setting. Mechanisms of DNA repair and the DNA damage response are reviewed to provide background for understanding novel approaches targeting DNA repair defects in this disease with DNA-damaging chemotherapeutic agents and poly(ADP-ribose) polymerase inhibitors. Ongoing studies, including those investigating the role of antiangiogenic therapies, are also reviewed. PMID- 20587405 TI - Prediction of benefit from adjuvant treatment in patients with breast cancer. AB - With the increasingly early diagnosis of breast cancer and the advent of breast tumor subtyping, the need for determining which patients need adjuvant therapy has become more pressing and more complex. While clinical and pathologic features to predict benefit are valuable, the use of molecular techniques to better determine which tumors will benefit from chemotherapy is expected to further improve outcomes, reduce long-term complications, and provide cost-effective care. We will review the primary tools in clinical use: Adjuvant!, Oncotype DX, and MammaPrint as well as intrinsic subtypes and the plans for their further assessment in the clinical trial setting. The expected benefit from these models are that treatment recommendations for women with early-stage breast cancer will become more individualized and thereby appropriate by combining standard clinicopathologic and molecular features. This concept is currently being evaluated in multiple well-designed clinical trials. PMID- 20587406 TI - Clinical updates on EGFR/HER targeted agents in early-stage breast cancer. AB - Recent updated reports from the large adjuvant trials in HER2-positive breast cancer indicate that the remarkable benefits of adding trastuzumab to chemotherapy appear, so far, to be sustained rather than transient. Other studies show that even small, node-negative, HER2-positive tumors carry some risk of recurrence and might benefit from trastuzumab-based adjuvant therapy. Evaluations of HER2 test results have examined the benefit of trastuzumab in cancers that exhibit focally positive gene amplification and also have raised the question of whether the criteria that correlate HER2 positivity with trastuzumab benefit in the adjuvant setting may be different from the criteria that apply in the treatment of metastatic disease. New results from trials combining targeted agents in the treatment of metastatic breast cancer provide strong rationale for the current adjuvant trials. In addition, neoadjuvant studies lend further support for combining targeted agents and may also provide an optimal setting to identify biomarkers that correlate with patient outcome. A new generation of therapies, including novel targeted agents and vaccines, is moving forward in clinical development and will be incorporated into adjuvant regimens in the future. PMID- 20587404 TI - Antiangiogenic therapies in early-stage breast cancer. AB - Angiogenesis, which is crucial for the growth and spread of cancer cells, has become an important target for antineoplastic therapies in a variety of malignant tumors. Vascular endothelial growth factor and its receptor promote formation of new blood vessels in tumors. Several drugs, most notably the monoclonal antibody bevacizumab, have been developed to inhibit this process. Clinical trials utilizing bevacizumab and other antiangiogenic drugs in metastatic breast cancer have demonstrated enhanced response rates and prolonged progression-free survival, though no overall survival benefit has been seen. Trials are now under way exploring the use of antiangiogenic agents in patients with early stage breast cancer. We performed a comprehensive review of the published literature (English language), US National Institutes of Health clinical trials registry (ClinicalTrials.gov), and established cooperative groups that revealed approximately 75 clinical trials, completed or ongoing, utilizing antiangiogenic drugs in early-stage breast cancer. A number of phase II trials in the neoadjuvant setting have reported preliminary results suggesting response rates similar to those seen with traditional anthracycline-plus-taxane combination regimens. Most of these early trials have not yet met any survival endpoints. Studies are also ongoing in the adjuvant setting, and these have not yet been reported. The toxicities associated with these agents are similar to those that have been reported in the metastatic trials. Most of these side effects are grade 1 or 2 and are easily manageable; however, there remain a small percentage of patients who sustain life-threatening vascular events, bleeding, or wound-healing complications. This number is significantly higher in patients receiving antiangiogenic drugs when compared with controls. While we eagerly await completion and results of this impressive portfolio of studies in early breast cancer with antiangiogenic agents, there is an urgent need for a more rational patient/antiangiogenic therapy selection with greater insight into predictive factors for toxicities, therapy efficacy, and clinical benefit. PMID- 20587408 TI - Lethal breast cancer. PMID- 20587409 TI - Optimizing chemotherapy regimens for patients with early-stage breast cancer. AB - While moving toward a personalized treatment approach for early breast cancer, it is clear that treatment must be tailored specifically to the tumor's and patient's characteristics. Understanding the tumor's molecular signature and using validated prognostic and predictive tools can assist the oncologist in providing the optimal therapy. Through a shared decision process, a treatment plan must be formulated based on the tumor's biologic phenotype, taking into consideration the patient's comorbidities and preferences. This review summarizes the available tools that can assist in this process and provides an overview of the chemotherapy regimens approved for the adjuvant treatment of patients with early-stage breast cancer. PMID- 20587410 TI - Risk of breast cancer in male BRCA2 carriers. AB - The risk of breast cancer for unaffected men who test positive for a BRCA2 mutation is based on very few retrospective studies. We have used both retrospective and prospective analysis in 321 families with pathogenic BRCA2 mutations. Three breast cancers occurred in male first-degree relatives after family ascertainment in 4140 years of follow-up suggesting a risk of breast cancer to 80 years of 8.9%. A second analysis excluding index cases identified 16 breast cancers in 905 first-degree male relatives on which Kaplan-Meier analysis was performed after assigning carrier status. This analysis confirmed that breast cancer risk in men was 7.1% (SE 5.2-8.6%) by age 70 years and 8.4% (SE 6.2-10.6%) by age 80 years. PMID- 20587411 TI - Multiple cutaneous squamous cell carcinomas in a patient with interferon gamma receptor 2 (IFN gamma R2) deficiency. AB - Disseminated squamous cell carcinoma (SCC) of the skin is exceedingly rare in children. SCC occurs after immunodeficiency from immunosuppression in organ transplant recipients or patients with HIV infection or leukaemia, but has not been reported in primary immunodeficiencies other than epidermodysplasia verruciformis. Interferon gamma receptor 2 (IFN gamma R2) deficiency is an exceedingly rare primary immunodeficiency, conferring almost selective predisposition to mycobacterial diseases. A disseminated, cutaneous SCC is described that occurred in a patient homozygous for a novel frameshift deletion at positions 949 and 950 (949delTG) in the IFNGR2 gene. The patient first presented at 1 year of age with disseminated Mycobacterium avium infection, with later infections of atypical mycobacteria (Mycobacterium fortuitum and Mycobacterium porcium). At 17 years of age, the patient developed multifocal SCC lesions on the face and both hands. Histopathological examination revealed well differentiated SCC. Despite local tumour excision, multiple lesions occurred and a large SCC on the right arm required amputation. The patient died at 20 years of age of disseminated SCC. Inherited disorders of IFN gamma mediated immunity may predispose patients to SCC. PMID- 20587412 TI - Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers. AB - BACKGROUND: Reported prevalence, penetrance and expression of deleterious mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2, may reflect differences in the clinical criteria used to select families for DNA testing. The authors have previously reported that clinical criteria are not sensitive enough to identify MMR mutation carriers among incident colorectal cancer cases. OBJECTIVE: To describe the sensitivity of the criteria when applied to families with a demonstrated MMR mutation. METHODS: Families with an aggregation of colorectal cancers were examined for deleterious MMR mutations according to the Mallorca guidelines. All families with a detected MMR mutation as of November 2009 were reclassified according to the Amsterdam and Bethesda criteria. RESULTS: Sixty-nine different DNA variants were identified in a total of 129 families. The original Amsterdam clinical criteria were met by 38%, 12%, 78% and 25% of families with mutations in MSH2, MSH6, MLH1 and PMS2, respectively. Corresponding numbers for the revised Amsterdam criteria were 62%, 48%, 87% and 38%. Similarly, each of the four clinical Bethesda criteria had low sensitivity for identifying MSH6 or PMS2 mutations. CONCLUSION: Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability. PMID- 20587413 TI - Replication of KIF21B as a susceptibility locus for multiple sclerosis. AB - BACKGROUND: Knowledge of genetic susceptibility to autoimmune disorders is growing exponentially. One of the messages emerging from these data is the growing overlap in genetic susceptibility to different autoimmune disorders. KIF21B is a member of the kinesin superfamily and was recently established as a susceptibility locus for inflammatory bowel disease and for multiple sclerosis. RESULTS: We here replicate the association with multiple sclerosis in a Belgian study population of 791 patients and 1098 controls. CONCLUSION: As SNPs in KIF21B increase risk for both inflammatory bowel disease and multiple sclerosis, this suggests a common pathway in the pathogenesis of these diseases. PMID- 20587414 TI - p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. AB - The packaging of newly replicated and repaired DNA into chromatin is crucial for the maintenance of genomic integrity. Acetylation of histone H3 core domain lysine 56 (H3K56ac) has been shown to play a crucial role in compaction of DNA into chromatin following replication and repair in Saccharomyces cerevisiae. However, the occurrence and function of such acetylation has not been reported in mammals. Here we show that H3K56 is acetylated and that this modification is regulated in a cell cycle-dependent manner in mammalian cells. We also demonstrate that the histone acetyltransferase p300 acetylates H3K56 in vitro and in vivo, whereas hSIRT2 and hSIRT3 deacetylate H3K56ac in vivo. Further we show that following DNA damage H3K56 acetylation levels increased, and acetylated H3K56, which is localized at the sites of DNA repair. It also colocalized with other proteins involved in DNA damage signaling pathways such as phospho-ATM, CHK2, and p53. Interestingly, analysis of occurrence of H3K56 acetylation using ChIP-on-chip revealed its genome-wide spread, affecting genes involved in several pathways that are implicated in tumorigenesis such as cell cycle, DNA damage response, DNA repair, and apoptosis. PMID- 20587415 TI - The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. AB - The S100B-p53 protein complex was discovered in C8146A malignant melanoma, but the consequences of this interaction required further study. When S100B expression was inhibited in C8146As by siRNA (siRNA(S100B)), wt p53 mRNA levels were unchanged, but p53 protein, phosphorylated p53, and p53 gene products (i.e. p21 and PIDD) were increased. siRNA(S100B) transfections also restored p53 dependent apoptosis in C8146As as judged by poly(ADP-ribose) polymerase cleavage, DNA ladder formation, caspase 3 and 8 activation, and aggregation of the Fas death receptor (+UV); whereas, siRNA(S100B) had no effect in SK-MEL-28 cells containing elevated S100B and inactive p53 (p53R145L mutant). siRNA(S100B) mediated apoptosis was independent of the mitochondria, because no changes were observed in mitochondrial membrane potential, cytochrome c release, caspase 9 activation, or ratios of pro- and anti-apoptotic proteins (BAX, Bcl-2, and Bcl X(L)). As expected, cells lacking S100B (LOX-IM VI) were not affected by siRNA(S100B), and introduction of S100B reduced their UV-induced apoptosis activity by 7-fold, further demonstrating that S100B inhibits apoptosis activities in p53-containing cells. In other wild-type p53 cells (i.e. C8146A, UACC-2571, and UACC-62), S100B was found to contribute to cell survival after UV treatment, and for C8146As, the decrease in survival after siRNA(S100B) transfection (+UV) could be reversed by the p53 inhibitor, pifithrin-alpha. In summary, reducing S100B expression with siRNA was sufficient to activate p53, its transcriptional activation activities, and p53-dependent apoptosis pathway(s) in melanoma involving the Fas death receptor and perhaps PIDD. Thus, a well known marker for malignant melanoma, S100B, likely contributes to cancer progression by down-regulating the tumor suppressor protein, p53. PMID- 20587416 TI - Human beta1-adrenergic receptor is subject to constitutive and regulated N terminal cleavage. AB - The beta(1)-adrenergic receptor (beta(1)AR) is the predominant betaAR in the heart, mediating the catecholamine-stimulated increase in cardiac rate and force of contraction. Regulation of this important G protein-coupled receptor is nevertheless poorly understood. We describe here the biosynthetic profile of the human beta(1)AR and reveal novel features relevant to its regulation using an inducible heterologous expression system in HEK293(i) cells. Metabolic pulse chase labeling and cell surface biotinylation assays showed that the synthesized receptors are efficiently and rapidly transported to the cell surface. The N terminus of the mature receptor is extensively modified by sialylated mucin-type O-glycosylation in addition to one N-glycan attached to Asn(15). Furthermore, the N terminus was found to be subject to limited proteolysis, resulting in two membrane-bound C-terminal fragments. N-terminal sequencing of the fragments identified two cleavage sites between Arg(31) and Leu(32) and Pro(52) and Leu(53), which were confirmed by cleavage site and truncation mutants. Metalloproteinase inhibitors were able to inhibit the cleavage, suggesting that it is mediated by a matrix metalloproteinase or a disintegrin and metalloproteinase (ADAM) family member. Most importantly, the N-terminal cleavage was found to occur not only in vitro but also in vivo. Receptor activation mediated by the betaAR agonist isoproterenol enhanced the cleavage in a concentration- and time-dependent manner, and it was also enhanced by direct stimulation of protein kinase C and adenylyl cyclase. Mutation of the Arg(31) Leu(32) cleavage site stabilized the mature receptor. We hypothesize that the N terminal cleavage represents a novel regulatory mechanism of cell surface beta(1)ARs. PMID- 20587417 TI - Contribution of the S5-pore-S6 domain to the gating characteristics of the cation channels TRPM2 and TRPM8. AB - The closely related cation channels TRPM2 and TRPM8 show completely different requirements for stimulation and are regulated by Ca(2+) in an opposite manner. TRPM8 is basically gated in a voltage-dependent process enhanced by cold temperatures and cooling compounds such as menthol and icilin. The putative S4 voltage sensor of TRPM8 is closely similar to that of TRPM2, which, however, is mostly devoid of voltage sensitivity. To gain insight into principal interactions of critical channel domains during the gating process, we created chimeras in which the entire S5-pore-S6 domains were reciprocally exchanged. The chimera M2 M8P (i.e. TRPM2 with the pore of TRPM8) responded to ADP-ribose and hydrogen peroxide and was regulated by extracellular and intracellular Ca(2+) as was wild type TRPM2. Single-channel recordings revealed the characteristic pattern of TRPM2 with extremely long open times. Only at far-negative membrane potentials ( 120 to -140 mV) did differences become apparent because currents were reduced by hyperpolarization in M2-M8P but not in TRPM2. The reciprocal chimera, M8-M2P, showed currents after stimulation with high concentrations of menthol and icilin, but these currents were only slightly larger than in controls. The transfer of the NUDT9 domain to the C terminus of TRPM8 produced a channel sensitive to cold, menthol, or icilin but insensitive to ADP-ribose or hydrogen peroxide. We conclude that the gating processes in TRPM2 and TRPM8 differ in their requirements for specific structures within the pore. Moreover, the regulation by extracellular and intracellular Ca(2+) and the single-channel properties in TRPM2 are not determined by the S5-pore-S6 region. PMID- 20587418 TI - Extracellular allosteric regulatory subdomain within the gamma subunit of the epithelial Na+ channel. AB - The activity of the epithelial Na(+) channel (ENaC) is modulated by Na(+) self inhibition, a down-regulation of the open probability of ENaC by extracellular Na(+). A His residue within the extracellular domain of gammaENaC (gammaHis(239)) was found to have a critical role in Na(+) self-inhibition. We investigated the functional roles of residues in the vicinity of this His by mutagenesis and analyses of Na(+) self-inhibition responses in Xenopus oocytes. Significant changes in the speed and magnitude of Na(+) self-inhibition were observed in 16 of the 47 mutants analyzed. These 16 mutants were distributed within a 22-residue tract. We further characterized this scanned region by examining the accessibility of introduced Cys residues to the sulfhydryl reagent MTSET. External MTSET irreversibly increased or decreased currents in 13 of 47 mutants. The distribution patterns of the residues where substitutions significantly altered Na(+) self-inhibition or/and conferred sensitivity to MTSET were consistent with the existence of two helices within this region. In addition, single channel recordings of the gammaH239F mutant showed that, in the absence of Na(+) self-inhibition and with an increased open probability, ENaCs still undergo transitions between open and closed states. We conclude that gammaHis(239) functions within an extracellular allosteric regulatory subdomain of the gamma subunit that has an important role in conferring the response of the channel to external Na(+). PMID- 20587419 TI - Sumoylation regulates interaction of FOG1 with C-terminal-binding protein (CTBP). AB - Erythropoietic and megakaryocytic programs are specified from multipotential progenitors by the transcription factor GATA1. FOG1, a GATA1-interaction partner, is critical for GATA1 function in several contexts by bringing multiple complexes into association with GATA1 to facilitate activation or repression of target genes. To further elucidate regulation of these associations by cellular and extracellular cues, we examined FOG1 for post-translational modifications. We found that FOG1 is SUMOylated and phosphorylated in erythroid cells in a differentiation-dependent manner. Removal of the SUMOylation sites in FOG1 does not impair nuclear localization, protein stability, or chromatin occupancy. However, SUMOylation of FOG1 modulates interactions with C-terminal binding protein family members, specifically promoting CTBP1 binding. Phosphorylation of FOG1 modulates SUMOylation and, therefore, indirectly regulates the CTBP interaction. Post-translational modification of FOG1 may contribute to control of co-occupancy by CTBP family members, the NuRD complex, and GATA1 at differentially regulated genes. PMID- 20587420 TI - A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes. AB - Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and metabolism. We report here the identification of pleckstrin homology-like domain family B member 1 (PHLDB1) as an insulin-responsive protein that enhances Akt activation. PHLDB1 contains a pleckstrin homology domain, which we show binds phosphatidylinositol PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), as well as a Forkhead-associated domain and coiled coil regions. PHLDB1 expression is increased during adipocyte differentiation, and it is abundant in many mouse tissues. Both endogenous and HA or GFP-tagged PHLDB1 displayed a cytoplasmic disposition in unstimulated cultured adipocytes but translocated to the plasma membrane in response to insulin. Depletion of PHLDB1 by siRNA inhibited insulin stimulation of Akt phosphorylation but not tyrosine phosphorylation of IRS-1. RNAi-based silencing of PHLDB1 in cultured adipocytes also attenuated insulin-stimulated deoxyglucose transport and Myc-GLUT4-EGFP translocation to the plasma membrane, whereas knockdown of the PHLDB1 isoform PHLDB2 failed to attenuate insulin-stimulated deoxyglucose transport. Furthermore, adenovirus-mediated expression of PHLDB1 in adipocytes enhanced insulin-stimulated Akt and p70 S6 kinase phosphorylation, as well as GLUT4 translocation. These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin. PMID- 20587421 TI - Essential role of the CBD1-CBD2 linker in slow dissociation of Ca2+ from the regulatory two-domain tandem of NCX1. AB - In NCX proteins CBD1 and CBD2 domains are connected through a short linker (3 or 4 amino acids) forming a regulatory tandem (CBD12). Only three of the six CBD12 Ca(2+)-binding sites contribute to NCX regulation. Two of them are located on CBD1 (K(d) = approximately 0.2 microM), and one is on CBD2 (K(d) = approximately 5 microM). Here we analyze how the intrinsic properties of individual regulatory sites are affected by linker-dependent interactions in CBD12 (AD splice variant). The three sites of CBD12 and CBD1 + CBD2 have comparable K(d) values but differ dramatically in their Ca(2+) dissociation kinetics. CBD12 exhibits multiphasic kinetics for the dissociation of three Ca(2+) ions (k(r) = 280 s(-1), k(f) = 7 s( 1), and k(s) = 0.4 s(-1)), whereas the dissociation of two Ca(2+) ions from CBD1 (k(f) = 16 s(-1)) and one Ca(2+) ion from CBD2 (k(r) = 125 s(-1)) is monophasic. Insertion of seven alanines into the linker (CBD12-7Ala) abolishes slow dissociation of Ca(2+), whereas the kinetic and equilibrium properties of three Ca(2+) sites of CBD12-7Ala and CBD1 + CBD2 are similar. Therefore, the linker dependent interactions in CBD12 decelerate the Ca(2+) on/off kinetics at a specific CBD1 site by 50-80-fold, thereby representing Ca(2+) "occlusion" at CBD12. Notably, the kinetic and equilibrium properties of the remaining two sites of CBD12 are "linker-independent," so their intrinsic properties are preserved in CBD12. In conclusion, the dynamic properties of three sites are specifically modified, conserved, diversified, and integrated by the linker in CBD12, thereby generating a wide range dynamic sensor. PMID- 20587422 TI - What nephrologists need to know about antiphospholipid syndrome. AB - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies (aCL) and/or evidence of circulating lupus anticoagulant (LA). The kidney is a major target organ in both primary and secondary APS. With the expanding spectrum of renal diseases associated with APS, and the impact of APS in ESRD care, this subject is of increasing relevance to nephrologists. This review describes the various clinical manifestations and histological features of this syndrome, with reference to the kidney. PMID- 20587423 TI - Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion. AB - BACKGROUND: We report autism in 3 out of 53 children with cystic or hyperechogenic kidneys and heterozygous 17q12 region deletion encompassing hepatocyte nuclear factor-1beta (HNF1B). RESULTS: They presented mental retardation, social interaction impairments, verbal and non-verbal communication deficits and stereotyped behaviours. Deletion size and location of breakpoints were similar to those reported in patients with renal disease/diabetes only. CONCLUSION: Reciprocal genomic rearrangements of the 17q12 region, reported in patients with mental retardation and epilepsy, could also be involved in autism. Nephrologists should be aware of the possibility of autism in patients with 17q12 deletion including HNF1B locus. PMID- 20587424 TI - Brain blood flow and velocity: correlations between magnetic resonance imaging and transcranial Doppler sonography. AB - OBJECTIVE: Because transcranial Doppler sonography (TCD) is unable to measure arterial diameter, it remains unproven whether the changes in cerebral blood velocity it measures are representative of changes in cerebral blood flow (CBF). Our study was designed to compare velocity changes with flow changes measured by two magnetic resonance imaging (MRI) techniques, perfusion MRI and arterial spin labeling (ASL), using flavanol-rich cocoa to induce CBF changes in healthy volunteers. METHODS: We enrolled 20 healthy volunteers aged 62 to 80 years (mean, 73 years). Each was studied at baseline and after drinking standardized servings of cocoa for 7 to 14 days. RESULTS: Changes in middle cerebral artery (MCA) flow by TCD were significantly correlated with changes in perfusion assessed by gadolinium-enhanced MRI (r = 0.63; P < .03). Measurements with ASL showed a stronger correlation with borderline significance. CONCLUSIONS: Changes in flow velocity in the MCA associated with drinking cocoa were highly correlated with changes in CBF measured by the two MRI techniques using the tracer gadolinium and ASL. These results validate Doppler measurements of CBF velocity as representative assessments of CBF. PMID- 20587425 TI - High-frequency sonographic measurements of true and false vocal cords. AB - OBJECTIVE: The purpose of this study was to prospectively identify the normal sonographic values of human true and false vocal cords. METHODS: In total, 229 healthy volunteers were divided into 8 groups according to their age and sex. High-frequency sonography was used to measure the length, width, and thickness of both true and false vocal cords. Measurements were compared between groups, and correlations with age were analyzed. Forty of the 229 volunteers also participated in reliability and reproducibility studies. RESULTS: The sonographic measurements had good reproducibility, with intraclass correlation coefficient ranges of 0.736 to 0.903 for interobserver reliability and 0.723 to 0.943 for intraobserver reliability. Measurements for the 3 parameters of both true and false vocal cords in male adults were greater than those in female adults (P < .001). The length, width, and thickness of true and false vocal cords in participants younger than 18 years were obviously correlated with age (r = 0.835 0.957; P < .001), but no significant correlation was found in the adult groups. The rates of visualization in male groups were significantly lower than those in female groups (P < .001) and gradually decreased with increasing age. CONCLUSIONS: Both true and false vocal cords can be shown by high-frequency sonography, which can quantitatively measure both true and false vocal cords with good reliability and reproducibility. PMID- 20587426 TI - Sonodynamic action of pyropheophorbide-a methyl ester in liver cancer cells. AB - OBJECTIVE: This study aimed to investigate the sonodynamic action of pyropheophorbide-a methyl ester (MPPa) in liver cancer cells to explore a novel therapeutic modality. METHODS: H22 cells were chosen as model cells to investigate the sonodynamic action of MPPa on liver cancer. The MPPa concentration was kept constant at 2 micromol/L, and the cells were subjected to ultrasound exposure at an intensity of 0.97 W/cm(2). Cytotoxicity was investigated 24 hours after ultrasound exposure. Apoptosis was evaluated using flow cytometry with annexin V-fluorescein isothiocyanate and propidium iodine staining and nuclear staining with Hoechst 33258. Reactive oxygen species (ROS) were analyzed using flow cytometry with 2,7-dichlorodihydrofluorescein diacetate staining. RESULTS: No significant dark cytotoxicity of MPPa was shown in the H22 cells at the concentration of 2 micromol/L. The cell death rate induced by ultrasound treatment was significantly higher in the presence of MPPa than in the absence of it (P < .05). Flow cytometry showed that the sonodynamic action of MPPa significantly increased the early and late apoptotic rates of the H22 cells. Nuclear condensation and an ROS increase were found after sonodynamic treatment. CONCLUSIONS: Our findings showed that MPPa-mediated sonodynamic action significantly enhanced death of H22 cells and the ROS level, suggesting that MPPa is a novel sonosensitizer and the sonodynamic action of MPPa might be a potential therapeutic modality in the management of liver cancer. PMID- 20587427 TI - Preoperative diagnosis of ovarian tumors using pelvic contrast-enhanced sonography. AB - OBJECTIVE: The purpose of this study was to assess the feasibility of using a contrast agent for the sonographic examination of adnexal tumors and identify discriminating parameters in the preoperative diagnosis of malignant tumors. METHODS: We conducted a prospective descriptive monocenter study that analyzed validated echographic criteria and parameters of the enhancement curve obtained by sonographic contrast agent injection. Patients included were referred for a second opinion after the discovery of a suspicious ovarian image. The final diagnosis was reached after surgery and an anatomopathologic examination. RESULTS: Fifty-two tumors were analyzed. Morphologic and Doppler criteria analyses were conducted as described in the literature. The significant parameters of the enhancement curve were the time-intensity curve total area and the duration of activity of the contrast agent during the first phase of decay (P < .002). The performance of the contrast agent was lower than that of the examiner's subjective diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.78 versus 0.80. When borderline tumors were eliminated, there was an inversion of this, with an AUC of 0.85 versus 0.73. The inclusion of contrast results in the examiner's diagnosis in the context of a bivariate model comparing malignant and borderline tumors with benign tumors provided an AUC of 0.88. CONCLUSIONS: Contrast-enhanced sonography improves preoperative diagnosis of ovarian tumors parameters. The significant parameters of the enhancement curve were significantly different for malignant and benign tumors. Borderline tumors contribute to a reduction of the discriminating capacity of the contrast agent. PMID- 20587428 TI - Abnormal ductus venosus flow in first-trimester fetuses with increased nuchal translucency: relationship with the type of cardiac defect? AB - OBJECTIVE: The purpose of this study was to evaluate ductus venosus flow velocities and a possible relationship with the type of cardiac defect in fetuses with increased nuchal translucency (NT). METHODS: Seventy-two fetuses with normal NT and 137 fetuses with increased NT (>95th percentile) were evaluated. The ductus venosus pulsatility index for veins (PIV), late diastolic velocity (velocity during atrial contraction [a-V]), and intracardiac velocities were evaluated. In cases of pregnancy termination, a postmortem examination was performed. Cardiac defects were grouped into septal defects, left and right inflow obstruction, left and right outflow obstruction, and other defects. Data were evaluated by multilevel analysis. RESULTS: A cardiac defect was found in 45 fetuses with increased NT. Fetuses with increased NT showed a higher ductus venosus PIV and a lower a-V compared to fetuses with normal NT (P < .05). Within the group of fetuses with increased NT, a higher PIV and a lower a-V were found in cases with a cardiac defect compared to cases with a normal heart (P < .001). No differences in PIV and a-V were found between the types of cardiac defects. Intracardiac velocities showed no differences between fetuses with normal and increased NT, irrespective of the presence of a cardiac defect. CONCLUSIONS: Ductus venosus flow velocities in fetuses with increased NT are not related to a certain type of cardiac defect. This indicates that the altered ductus venosus flow velocities found in fetuses with increased NT cannot be explained by cardiac failure due to a specific altered cardiac anatomy. PMID- 20587429 TI - Comparison of single versus multiple echogenic foci in the fetal heart regarding risk of aneuploidy. AB - OBJECTIVE: The purpose of this study was to investigate whether multiple echogenic cardiac foci (ECF) are associated with an increased risk of fetal trisomy 21 in our patient population. METHODS: During a span of 38 months, all women found to have an ECF on obstetric sonography were identified as study patients and grouped into single- and multiple-ECF groups. Age- and race-matched patients were identified as a control group. Fetal anatomic sonographic examinations were assessed for other markers of aneuploidy and major abnormalities. The baseline risk for trisomy 21 was assessed by maternal serum screening or age alone if no serum screening had been performed. Trisomy 21 was assessed by amniocentesis or clinically at birth. Both univariate and multivariate analyses were used to assess for associations with trisomy 21. RESULTS: Six of 71 patients (8.5%) with multiple ECF and 1 of 171 patients (0.6%) with a single ECF had trisomy 21. One of 242 control patients (0.4%) had trisomy 21. Logistic regression found multiple ECF (P < .008), the presence of a major finding or multiple minor findings (P = .0012), and a baseline risk for trisomy 21 of greater than 1 in 100 (P = .003) as independent associations with trisomy 21. CONCLUSIONS: Our results suggest that finding multiple ECF is a stronger predictor of trisomy 21 than what is described for a single ECF. PMID- 20587430 TI - Estimation of fetal weight in fetuses with abdominal wall defects: comparison of 2 recent sonographic formulas to the Hadlock formula. AB - OBJECTIVE: Estimation of fetal weight is particularly challenging in fetuses with abdominal wall defects (AWDs). We sought to compare the accuracy and screening efficiency for intrauterine growth restriction (IUGR) of 2 recent sonographic formulas to those of the Hadlock formula (Am J Obstet Gynecol 1985; 151:333-337) in fetuses with AWDs. METHODS: This was a retrospective cohort study of fetuses with AWDs. Fetuses with sonographically estimated fetal weights (EFWs) within 14 days before delivery were included. Using the individual biometric measurements, EFWs were calculated using the Honarvar (Int J Gynaecol Obstet 2001; 73:15-20; femur length [FL]), Siemer (Ultrasound Obstet Gynecol 2008; 31:397-400; FL, biparietal diameter [BPD], and occipitofrontal diameter), and Hadlock (BPD, head circumference, abdominal circumference, and FL) formulas. The calculated EFWs were adjusted for interval growth between the dates of sonography and delivery using published sonographic fetal growth velocity standards. Accuracy and screening efficiency for IUGR were compared. RESULTS: Seventy-six fetuses were included: 53 with gastroschisis and 23 with omphalocele. The median gestational age at delivery was 36.6 weeks (range, 25.0 to 39.0 weeks). The Siemer formula had the lowest mean percentage error (-2.5% [95% confidence interval (CI), -6.2% to +1.2%]) without systematic bias (P = .182). The Hadlock formula had the highest precision (random error, 11.4%), sensitivity (91%), and accuracy for predicting IUGR (85% [95% CI, 77% to 94%]). CONCLUSIONS: None of the 3 sonographic formulas is ideal for estimating fetal weight in fetuses with AWDs. The Siemer formula should be used when accuracy in the absolute EFW is the goal. For the purpose of making the more clinically relevant diagnosis of IUGR, use of the Hadlock formula is justified. PMID- 20587431 TI - Effect of a gel retainment dam on automated ultrasound coverage in a dual modality breast imaging system. AB - OBJECTIVE: The goal of this work was to evaluate a possible improvement in ultrasound coverage for a dual-modality breast imaging system in the mammographic geometry. METHODS: A pilot study was performed to evaluate use of a rubber dam to retain ultrasound gel and improve imaging coverage at the breast periphery on a combined imaging system consisting of an ultrasound scanner and a digital x-ray tomosynthesis unit. Several dams were constructed to encompass the shapes of various sizes of compressed breasts. Visual tracings of the breast-to-paddle contact area and breast periphery were made for 8 breasts to estimate coverage area. Two readers independently reviewed the resulting images and were asked to rate the overall breast image quality. RESULTS: The percentages of breast in contact with the paddle were greater (P < .01) and the linear dimensions of breast in contact with the paddle were larger (P < .05) with the rubber dam than without it. With the dam, the mean estimated area of the breast in contact with the paddle increased 14%, whereas the mean increase in the fraction of the total breast area in contact with paddle was 30%. The difference was due to the mean total projected area of the breast decreasing 12% as the dam was pressed against it. The image quality of automated ultrasound with the rubber dam was consistently judged to be superior to that without the dam. CONCLUSIONS: This method can enhance the absolute and percentage area of the breast in contact with the paddle, reducing noncontact gaps at the breast periphery. Gently pressing the breast periphery with the dam inserted toward the chest wall improves coverage in automated breast ultrasound scanning. PMID- 20587432 TI - Use of quantitative ultrasound for identifying low bone density in older people. AB - OBJECTIVE: This study examined criterion, convergent, and discriminant validities of quantitative ultrasound (QUS) for identifying low bone density among people aged 55 years and older in Taiwan. METHODS: We recruited 453 community-dwelling volunteers and 30 patients with lower extremity fractures. Bone density was assessed using both calcaneal QUS and femoral neck dual-energy x-ray absorptiometry (DXA). Two QUS parameters, speed of sound (SOS) and broadband ultrasound attenuation (BUA), were also used to estimate heel bone mineral density (HBMD). RESULTS: Using DXA as the criterion for identifying low bone density (DXA T score of 1.0 or lower), likelihood ratios for BUA and SOS at the 50th percentile and HBMD for men were 1.50, 1.75, and 1.28, respectively; the counterparts for women were 1.54, 2.13, and 1.29. As for identifying osteoporosis (DXA T score of -2.5 or lower), higher likelihood ratios of the 3 QUS parameters were gained. For convergent validity, Pearson correlation coefficients for DXA with BUA, SOS, and HBMD ranged from 0.40 to 0.43 for men and from 0.48 to 0.53 for women. For the ability to discriminate men and women with lower extremity fractures from those without, no significant differences in the area under the receiver operating characteristic curve were detected between BUA, SOS, and HBMD and DXA after adjusting for age, body mass index, fall history, and current smoking. CONCLUSIONS: Although having very good convergent and discriminant validities and fair criterion validity, calcaneal QUS may be a screening tool for identifying low bone density. PMID- 20587433 TI - Sonographic appearances of Chinese intrauterine devices. AB - OBJECTIVE: The purpose of this presentation is to familiarize physicians about the different types of intrauterine devices (IUDs) used in China. METHODS: The characteristic features and the sonographic appearances of the different types of IUDs commonly used in China are described. RESULTS: The stainless steel ring is the most commonly used IUD in China. However, various different types of copper bearing IUDs are gaining popularity. Most Chinese IUDs do not have an attached thread and are more difficult to remove than the IUDs commonly used in North America. Also, most Chinese IUDs have a distinct sonographic appearance; therefore, sonography can play an important role when assessing a woman who has a retained Chinese IUD or has a complication associated with the IUD. CONCLUSIONS: Knowledge about the different types of Chinese IUDs will enable physicians to provide optimal care to their patients. PMID- 20587435 TI - Cross-imaging platform comparison of ultrasonic backscatter coefficient measurements of live rat tumors. AB - OBJECTIVE: To translate quantitative ultrasound (QUS) from the laboratory into the clinic, it is necessary to demonstrate that the measurements are platform independent. Because the backscatter coefficient (BSC) is the fundamental estimate from which additional QUS estimates are calculated, agreement between BSC results using different systems must be demonstrated. This study was an intercomparison of BSCs from in vivo spontaneous rat mammary tumors acquired by different groups using 3 clinical array systems and a single-element laboratory scanner system. METHODS: Radio frequency data spanning the 1- to 14-MHz frequency range were acquired in 3 dimensions from all animals using each system. Each group processed their radio frequency data independently, and the resulting BSCs were compared. The rat tumors were diagnosed as either carcinoma or fibroadenoma. RESULTS: Carcinoma BSC results exhibited small variations between the multiple slices acquired with each transducer, with similar slopes of BSC versus frequency for all systems. Somewhat larger variations were observed in fibroadenomas, although BSC variations between slices of the same tumor were of comparable magnitude to variations between transducers and systems. The root mean squared (RMS) errors between different transducers and imaging platforms were highly variable. The lowest RMS errors were observed for the fibroadenomas between 4 and 5 MHz, with an average RMS error of 4 x 10(-5) cm(-1)Sr(-1) and an average BSC value of 7.1 x 10(-4) cm(-1)Sr(-1), or approximately 5% error. The highest errors were observed for the carcinoma between 7 and 8 MHz, with an RMS error of 1.1 x 10(-1) cm(-1)Sr(-1) and an average BSC value of 3.5 x 10(-2) cm(-1)Sr(-1), or approximately 300% error. CONCLUSIONS: This technical advance shows the potential for QUS technology to function with different imaging platforms. PMID- 20587436 TI - Difficult management of a rapidly growing benign phyllodes tumor in a 49-year-old woman. PMID- 20587434 TI - Should bilateral uterine artery notching be used in the risk assessment for preeclampsia, small-for-gestational-age, and gestational hypertension? AB - OBJECTIVE: The purpose of this study was to determine the value of bilateral uterine artery notching in the second trimester in the risk assessment for preeclampsia, gestational hypertension, and small-for-gestational-age (SGA) without preeclampsia. METHODS: This prospective cohort study included 4190 singleton pregnancies that underwent ultrasound examination between 23 and 25 weeks' gestation. The 95th percentiles of the mean pulsatility index (PI) and resistive index (RI) of both uterine arteries were calculated. Multivariable logistic regression analyses were performed to determine if bilateral uterine artery notching is an independent explanatory variable for the occurrence of preeclampsia, early-onset preeclampsia (34 weeks), gestational hypertension, and delivery of an SGA neonate without preeclampsia, while controlling for confounding factors. RESULTS: (1) The prevalence of preeclampsia, early-onset preeclampsia, late-onset preeclampsia, SGA, and gestational hypertension were 3.4%, 0.5%, 2.9%, 10%, and 7.9%, respectively; (2) 7.2% of the study population had bilateral uterine artery notching; and (3) bilateral uterine artery notching was an independent explanatory variable for the development of preeclampsia (odds ratio [OR], 2.1; 95% confidence interval [CI],1.28-3.36), early-onset preeclampsia (OR, 4.47; 95% CI, 1.50-13.35), and gestational hypertension (OR, 1.50; 95% CI, 1.02-2.26), but not for late-onset preeclampsia or SGA. CONCLUSIONS: Bilateral uterine notching between 23 and 25 weeks' gestation is an independent risk factor for the development of early-onset preeclampsia and gestational hypertension. Thus, bilateral uterine artery notching should be considered in the assessment of risk for the development of these pregnancy complications. PMID- 20587437 TI - Asymptomatic metastatic melanoma of the gallbladder diagnosed with contrast enhanced ultrasonography. PMID- 20587438 TI - Exophytic duodenal carcinoma mimicking a pancreatic tumor on sonography. PMID- 20587439 TI - Transcranial sonographic findings in Wilson disease. PMID- 20587440 TI - Congenital intracranial teratoma: prenatal diagnosis and vaginal delivery. PMID- 20587441 TI - How to make a cheap and simple prostate phantom. PMID- 20587442 TI - Outcome following hip fracture: post-discharge residence and long-term mortality. PMID- 20587444 TI - ProstaCaid induces G2/M cell cycle arrest and apoptosis in human and mouse androgen-dependent and-independent prostate cancer cells. AB - The anticancer effects of ProstaCaid, a novel integrative blend of vitamins, minerals, multiherb extracts, and derivatives, were tested in human and mouse androgen-dependent (AD) and -independent (AI) prostate cancer cell lines. ProstaCaid shows growth inhibitory effects on both human and mouse AD prostate cancer cells (LNCaP and CASP 2.1) and AI prostate cancer cells (PC3 and CASP 1.1) in a dose-/time-dependent manner. Consistently, long-term treatment with ProstaCaid also reduced colony formation capacities of prostate cancer cells. Flow cytometry assays revealed that ProstaCaid induces G2/M arrest and apoptosis in LNCaP and PC3 cells after 72 hours of treatment. Immunoblotting assay demonstrated that 25 microg/mL of ProstaCaid treatment resulted in (1) the reduction of cyclin D1, cyclin B1, and Cdc2 expression in a time-dependent way; (2) increase in p21(WAF1/Cip1) as early as 12 hours after the treatments in PC3 cells and reduction to base line at the 72-hour time point; and (3) repression of Bcl-2, BclxL, and induction of Bim as well as the cleavages of caspase-3 and poly(ADP-ribose) polymerase (PARP) at 72 hours of treatment, suggesting caspase-3 dependent apoptosis. Moreover, ProstaCaid suppressed activation of AKT and MAPK signaling pathways in PC3 and LNCaP cells by reducing phosphorylation levels of AKT, its downstream target S6 ribosomal protein and GSK3beta, and ERK1/2, respectively. In summary, these findings strongly suggest that ProstaCaid may be a potential chemopreventive and therapeutic agent for both AD and, more importantly, AI prostate cancer. PMID- 20587445 TI - Oxymatrine inhibits development of morphine-induced tolerance associated with decreased expression of P-glycoprotein in rats. AB - The effect of oxymatrine on the development of tolerance to the antinociceptive effects of morphine was investigated in rats. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily administration of oxymatrine premorphine (10/20/30 mg/kg). High doses of oxymatrine inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist memantine) while also increasing the antinociceptive effects. A high dose of oxymatrine (30 mg/kg) also significantly inhibited the dramatic increase in expression of morphine-induced P-glycoprotein (P-gp), an ATP-dependent efflux pump acting at the blood-brain barrier, by Western blot analysis. Furthermore, these studies suggest that P-gp modulates the development of morphine tolerance while not affecting the magnitude of the analgesic effect of morphine. These results imply that oxymatrine prevention of the development of tolerance of morphine may be related to a considerable inhibition of P-gp expression. In contrast, the authors' data suggest that the mechanism of oxymatrine enhancement of morphine's analgesic effects is not associated with increase in the level of expression of P-gp. However, they believe that their findings can be used by researchers to develop therapies that will allow patients to take morphine without becoming tolerant of its benefits. PMID- 20587448 TI - Substance abuse among high-risk sexual offenders: do measures of lifetime history of substance abuse add to the prediction of recidivism over actuarial risk assessment instruments? AB - There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has been found to be related to recidivism among sexual offenders. To investigate whether lifetime history of substance abuse adds to prediction over and above actuarial instruments alone, several measures of substance abuse were administered in conjunction with the Sex Offender Risk Appraisal Guide (SORAG). The SORAG was found to be the most accurate actuarial instrument for the prediction of serious recidivism (i.e., sexual or violent) among the sample included in the present investigation. Complete information, including follow-up data, were available for 250 offenders who attended the Regional Treatment Centre Sex Offender Treatment Program (RTCSOTP). The Michigan Alcohol Screening Test (MAST) and the Drug Abuse Screening Test (DAST) were used to assess lifetime history of substance abuse. The results of logistic regression procedures indicated that both the SORAG and the MAST independently added to the prediction of serious recidivism. The DAST did not add to prediction over the use of the SORAG alone. Implications for both the assessment and treatment of sexual offenders are discussed. PMID- 20587449 TI - Blaming the victim and exonerating the perpetrator in cases of rape and robbery: is there a double standard? AB - Research in legal decision making has demonstrated the tendency to blame the victim and exonerate the perpetrator of sexual assault. This study examined the hypothesis of a special leniency bias in rape cases by comparing them to cases of robbery. N = 288 participants received descriptions of rape and robbery of a female victim by a male perpetrator and made ratings of victim and perpetrator blame. Case scenarios varied with respect to the prior relationship (strangers, acquaintances, ex-partners) and coercive strategy (force vs. exploiting victim intoxication). More blame was attributed to the victim and less blame was attributed to the perpetrator for rape than for robbery. Information about a prior relationship between victim and perpetrator increased ratings of victim blame and decreased perceptions of perpetrator blame in the rape cases, but not in the robbery cases. The findings support the notion of a special leniency bias in sexual assault cases. PMID- 20587450 TI - Controlling for selection effects in the relationship between child behavior problems and exposure to intimate partner violence. AB - This article used the Project on Human Development in Chicago Neighborhoods (PHDCN) data to examine the relationship between exposure to intimate partner violence (IPV) and child behavior problems (externalizing and internalizing), truancy, grade repetition, smoking, drinking, and use of marijuana. Longitudinal data analysis was conducted on 1,816 primary caregivers and their children. Fixed effects regression models were employed to address concerns with selection bias. IPV was associated with significantly greater internalizing behavior, externalizing behavior, and truancy. Findings from age interaction models suggested that the relationship between IPV and child behavior problems may attenuate as the age of the child at time of exposure increases. PMID- 20587451 TI - The psychosocial consequences of child sexual abuse in Ethiopia: a case-control comparative analysis. AB - Child sexual abuse (CSA) continues to be a pressing public health concern around the globe. Few existing reports, however, indicate the alarming rate at which the problem is increasing in sub-Saharan Africa. The present study is designed to investigate the psychosocial consequences of sexual abuse among child survivors in Ethiopia who were abused mainly through early marriage, rape, and child prostitution. Data are collected from 318 such CSA survivors-and 318 matched, non sexually abused, normal controls- using the Children's Impact of Traumatic Events Scale-Revised and the Rosenberg Self-Esteem Scale. The results reveal the CSA survivors to be significantly more symptomatic than the control group: They demonstrated a lower degree of social support, a lower degree of empowerment, as well as a higher degree of guilt and increased likelihood of viewing the world as dangerous. Finally, these CSA survivors show a lower degree of positive self worth than their non-sexually abused counterparts. These findings have important implications for the formulation of appropriate preventions and interventions to be undertaken by various stakeholders ranging from family to policy makers. PMID- 20587452 TI - Co-occurrence of intimate partner violence and child abuse in Hong Kong Chinese families. AB - This study examines the prevalence of co-occurrence of intimate partner violence (IPV) and child abuse and neglect (CAN) in a cohort of Chinese parents drawn from a large representative sample in Hong Kong. It also investigates the risk factors for CAN with a special emphasis on the role of IPV. A subsample of 2,363 parents was invited to complete the Conflict Tactics Scale and a demographic questionnaire examining the risk factors for CAN. Results show that among the perpetrators of child maltreatment, 37% and 36%, respectively, admitted they had been perpetrators and victims of IPV over their lifetime. Physical and psychological violence between spouses were the characteristics most significantly associated with child maltreatment. This suggests that intervention for CAN should include an assessment of IPV history. Integrative treatment for children suffering from CAN and interparental violence may be considered in intervention programs to combat CAN and IPV. PMID- 20587453 TI - Childhood sexual abuse associated with dating partner violence and suicidal ideation in a representative household sample in Hong Kong. AB - This study investigated the prevalence and impact of childhood sexual abuse (CSA) on future intimate partner violence (IPV) in dating relationship in Hong Kong, China. A total of 1,154 Chinese adult respondents engaged in dating relationships were interviewed face-to-face about their CSA histories, childhood witnessing of parental violence, adult sexual victimization (ASV) by others and IPV victimization with their current dating partner. Self-reports also measured levels of suicidal ideation, self-esteem, and demographic details. Overall, 1.7% reported some form of CSA with a higher percentage being women. No gender differences were found in the prevalence of either ASV or IPV. Results showed that CSA had an independent effect on physical IPV and suicidal ideation. The odds of IPV were increased by behavioral and psychological factors of victims such as alcohol and drug abuse, sex with partner, and low self-esteem. The odds of suicidal ideation were also increased by drug abuse, childhood witnessing of parental psychological aggression, and low self-esteem. Clinical implications of results included screening for CSA victims and suicidal victims when treating IPV patients, tailoring treatment according to individual IPV victim's problems, correcting behaviors that are associated with risks of IPV, such as engagement in casual sex and substance abuse, and focusing not only on tangible services but also on the social and psychological aspects that are placing the victims at risk for IPV. PMID- 20587454 TI - The prevalence of the Middle-Eastern extreme ideologies among some Canadians. AB - A total of 183 Canadian participants of different religious backgrounds completed the Belief Diversity Scale (BDS). The BDS is an 80-item, 6-subscale instrument designed to quantitatively measure the religious attitudes, beliefs, and ideologies of Middle-Eastern extremists' on risk areas that are reported in the literature. The results demonstrated the reliability and validity of the BDS as well as indicated the prevalence of Middle-Eastern extremists' ideologies among Muslim Canadians. Results were similar to those obtained from similar study completed on South African participants. These findings suggested that the BDS has the potential to be used as an objective tool to measure Middle-Eastern religious extremism. PMID- 20587455 TI - Why doesn't he leave? Relationship continuity and satisfaction among male domestic violence offenders. AB - In contrast to the extensive literature on women's decisions to leave violent relationships, there is little research examining relationship continuity from the offending male's perspective. Similarly, research exploring relationship satisfaction in men arrested for intimate partner violence (IPV) is lacking, despite the fact that dissatisfaction appears to increase risk for future IPV. The present study explored these issues using a large sample of men who were recently convicted of violence toward a female intimate partner (N = 1,130). More than half of the men (59%) reported that they were continuing or planning to continue their relationship. Factors associated with relationship continuity included older age, being married to the victim, having children together, attributing less blame to the victim for the recent offense, and having a childhood history of family violence. Among men who were continuing their relationship, low relationship satisfaction was predicted by having children, expressing hostile attitudes toward women, being jealous, blaming the victim for the arrest incident, and describing the victim as aggressive. Implications of the findings for clinical practice and research are discussed. PMID- 20587456 TI - Individual and situational influences on men's responses to dating and social situations. AB - This study employed multilevel modeling to evaluate individual and situational influences on men's responses to hypothetical dating and social situations. Three hundred and fifty college men completed measures assessing their propensity for sexual aggression and provided written responses to 10 written vignettes, each of which was followed by four statements provided by women that varied in their degree of effectiveness in decreasing victimization risk. Rape-supportive attitudes, poor heterosocial perception, earlier age of first sexual experience, and number of lifetime sexual partners were significant predictors of sexually aggressive responses. The presence of alcohol use, social isolation, relationship intimacy, and less effective responses from the woman involved also were significant predictors of sexually aggressive responses. Certain individual risk factors (i.e., poor heterosocial perception, rape-supportive attitudes) showed a stronger relationship to sexually aggressive responses in the context of situational risk factors (i.e., alcohol use, isolation). These findings indicate the importance of assessing both individual and situational influences on men's risk for engaging in sexually aggressive behavior. PMID- 20587457 TI - Concurrent and long-term impact of intimate partner violence on employment stability. AB - Previous research suggests that experiencing intimate partner violence (IPV) may negatively affect employment outcomes. This study explores the relationship between IPV and employment stability both concurrently and longitudinally among a sample of 512 predominantly Asian American and Pacific Islander young women living in Hawaii. Women in this study were identified as being at risk of child maltreatment. About half of women indicated that their current relationship status was married or living together. More than two-thirds of women had graduated from high school and half had worked in the past year. The study explored the concurrent association of IPV and employment by assessing them simultaneously over a 12 month time period. The study examined the longitudinal impact of IPV by analyzing violence at two time points as predictors of unstable employment 6 to 8 years later. The study also explored the mediating effects of depression. Study results demonstrated both concurrent and longitudinal negative associations of IPV with employment stability. Women who experienced violence were more likely to be experiencing unstable employment concurrently. Women who experienced IPV at one point in time had lower levels of employment stability six years later. This decrease was partially mediated by experiencing depressive symptoms. Women who identified their primary ethnicity as Native Hawaiian or Pacific Islander were much more likely to experience unstable employment than Asian American women. More research is needed to explore the roles of mental health, race and ethnicity, and types of violence in the relationship between IPV and employment. PMID- 20587458 TI - Latent profiles of risk among a community sample of men: implications for sexual aggression. AB - Of the proposed theoretical explanations for the perpetration of sexual assault, Malamuth's confluence theory remains the most prominent. Further development of this theory has incorporated alcohol use into the original pathways of impersonal sex and hostile masculinity. This study uses data from a nationwide online survey (n = 289) to examine the relationship of these three risk factors to sexual aggression using person-oriented methods, specifically latent profile analysis (LPA). Four statistically significant risk profiles were identified: low risk, moderate impersonal sex, high hostile masculinity, and high on all risk. All groups with elevated risk factors reported increased levels of sexual aggression. Groups 3 and 4 reported the highest levels. Implications for intervention and research are discussed. PMID- 20587459 TI - Aggression in sexually abused trafficked girls and efficacy of intervention. AB - The broad objective of this study was to understand the incidence and severity of aggression among sexually abused girls who were trafficked and who were then further used for commercial sexual exploitation (referred to subsequently as sexually abused trafficked girls). In addition, the impact of counseling for minimizing aggression in these girls was investigated. A group of 120 sexually abused trafficked Indian girls and a group of 120 nonsexually abused Indian girls, aged 13 to 18, participated in the study. The sexually abused trafficked girls were purposively selected from four shelters located in and around Kolkata, India. The nonsexually abused girls were selected randomly from four schools situated near the shelters, and these girls were matched by age with the sexually abused trafficked girls. Data were collected using a Background Information Schedule and a standardized psychological test, that is, The Aggression Scale. Results revealed that 16.7% of the girls were first sexually abused between 6 and 9 years of age, 37.5% between 10 and 13 years of age, and 45.8% between 14 and 17 years of age. Findings further revealed that 4.2% of the sexually abused trafficked girls demonstrated saturated aggression, and 26.7% were highly aggressive, that is, extremely frustrated and rebellious. Across age groups, the sexually abused trafficked girls suffered from more aggression (p < .05), compared with the nonvictimized girls. Psychological interventions, such as individual and group counseling, were found to have a positive impact on the sexually abused trafficked girls. These findings should motivate counselors to deal with sexually abused children. It is also hoped that authorities in welfare homes will understand the importance of counseling for sexually abused trafficked children, and will appoint more counselors for this purpose. PMID- 20587460 TI - Gender differences in depression and anxiety among victims of intimate partner violence: the moderating effect of shame proneness. AB - The current study examined the moderating role of shame proneness on the association between physical, psychological, and sexual intimate partner violence victimization and depressive and anxious symptoms among male and female college students (N = 967). Students completed self-report measures of dating violence, depression, anxiety, and shame proneness. Results showed that shame proneness moderated the association between all forms of victimization and mental health symptoms. A three-way interaction revealed that sexual victimization predicted symptoms of anxiety to a greater extent for men than for women at high levels of shame proneness. Furthermore, results showed that gender moderated the association between physical and psychological victimization and health outcomes, such that victimization was related to increased depressive and anxious symptoms for men but not for women. Interpretations of these findings are discussed in relation to violence interventions, including primary prevention, and men's health. PMID- 20587461 TI - Intimate partner violence among general and urban poor populations in Kathmandu, Nepal. AB - Comparative studies are lacking on intimate partner violence (IPV) between urban poor and general populations. The objective of this study is to identify the prevalence and risk factors of physical IPV among the general and poor populations in urban Nepal. A cross-sectional study was conducted by structured questionnaire interview. Participants included 905 ever-married women in Kathmandu aged 15 to 49 years. Of the 905 participants, 680 were randomly selected from general population and 225 were recruited from urban poor population, who lived in purposively selected two communities. The prevalence and association between ever experiencing physical IPV and sociodemographic variables were examined. Results showed that the prevalence of physical IPV was 33.8% among the urban poor population (n = 225) and 19.9% among the general population (n = 680; p < .01). Several factors were significantly associated with physical IPV in both populations: the frequency of the husband's drinking, polygyny, and lower household economic status. However, two factors were associated with physical IPV only among the general population: the husband's lower educational level and early marriage. The conclusions of this study are that compared to the general population, the urban poor population showed a significantly higher prevalence of physical IPV and differences in the associated risk factors. The urban poor population requires focused data collection as well as tailored interventions to reduce IPV. PMID- 20587462 TI - Association between early marriage and intimate partner violence in India: a focus on youth from Bihar and Rajasthan. AB - The relationship between intimate partner violence (IPV) and early marriage is explored using the 2005-2006 India National Family Health Survey (NFHS-3). The NFHS-3 collected data from a representative sample of women and men in India with a large enough sample size to have a representative sample at the state level. The focus is on youth from Bihar and Rajasthan, two states with high IPV and early marriage. Multivariate logistic regression analyses demonstrate that women aged 20 to 24 who married before age eighteen, the legal age at marriage in India, are more likely to have ever experienced IPV in their lifetime and recently experienced IPV (in the last 12 months) than their counterparts who married later. The results were significant in Rajasthan but not in Bihar. To reduce IPV, targeted efforts must be made to decrease the proportion of India's girls who are married under the legal age of marriage. PMID- 20587463 TI - Outcomes of child sexual abuse as predictors of later sexual victimization. AB - The association between a history of child sexual abuse (CSA) and specific negative outcomes (attachment, feelings of power, and self-esteem) was explored as was the relationship between those negative outcomes and sexual victimization during the first semester of college. Two groups of freshman college women (67 who had experienced CSA and 55 who had not) completed measures of attachment, feelings of power, and self-esteem at the beginning of their freshman year of college. At the end of their first semester of college, participants (n = 93) provided information about whether they had been sexually assaulted during their first semester of college. The results indicated that participants in the CSA group did not differ on reported attachment anxiety, attachment avoidance, feelings of power, or self-esteem as compared to the control group. However, participants in the CSA group were more like to be sexually victimized during their first semester of college. Finally, logistic regression indicated that the negative outcomes of CSA were significantly related to sexual victimization during the first semester of college, with attachment anxiety playing an important role. Theoretical and practical implications of the findings are discussed. PMID- 20587464 TI - Victim resistance in child sexual abuse: a look into the efficacy of self protection strategies based on the offender's experience. AB - This study examines the efficacy, as experienced by offenders with their victim, of self-protection strategies used in child sexual abuse cases. It also investigates whether the efficacy of self-protection varies according to victim characteristics. The sample consists of 94 adult offenders who sexually abused a single child and who agreed to provide confidential self-report data on the efficacy of self-protection strategies used by their victim. Strategies taken into account are: (1) yelling or screaming, (2) fighting back, (3) saying no, (4) saying they didn't want to, (5) crying, (6) telling someone else about the abuse, (7) saying they were scared, (8) demanding to be left alone, (9) saying they would tell someone, (10) saying that people are not supposed to touch their private parts, (11) trying to get away, and (12) yelling for help. Saying that they do not want to have sexual contact and saying "no" to the offender are the most effective strategies. Because they are more likely to use self-protection initially, younger girls are also more likely to prevent episodes of abuse than older girls. PMID- 20587465 TI - IPV among adolescent reproductive health patients: the role of relationship communication. AB - Population-specific data on factors that affect intimate partner violence (IPV) are needed on female adolescents and young adults, a cohort at greatest risk of IPV in the United States (Rennison, 2001). Studies have frequently overlooked the role of relationship communication as a gatekeeper to IPV (Ridley & Feldman, 2003). To address this gap, negative binomial regression was conducted with data from a 2004 survey of 618 women aged 15 to 24 seeking care at an urban reproductive health facility. Findings suggest that, within the previous year, verbal aggression by either partner was associated with physical violence by either or both partners, and verbal reasoning was negatively correlated with physical violence. Bidirectional and unidirectional IPV relationships may employ communication strategies differently. PMID- 20587466 TI - Can norm theory explain the effects of victim age and level of physical maturity on perceptions of child sexual abuse? AB - The present study examines the effects of victim age, victim physical maturity, and respondent gender on attributions toward victims, perpetrator, and the nonoffending members of the victim's family in a hypothetical child sexual abuse (CSA) case. Participants read a brief CSA vignette in which the male perpetrator (a school caretaker) sexually abuses a student in the school changing rooms. The victim was depicted as either a 12- or 15-year-old girl who, in terms of physical maturity, was either pre- or postpubescent. Separate 2 * 2 * 2 ANOVAs were performed on the dependent variables. Results conformed broadly to the study's predictions with younger victims being viewed more negatively than older victims and the victim's physical appearance being viewed as more encouraging of CSA for the younger than for the older girl. Female participants were more likely to endorse the belief that the younger victim should have fought back and that the prepubescent 15-year-old victim should have fought back more than her postpubescent counterpart. While attributions toward the perpetrator and victim's family did not differ across conditions for women, men tended to blame the perpetrator more when victims were younger and the family more when victims were less physically mature. Findings are discussed in relation to norm theory principles, just world theory, and the defensive attribution hypothesis. PMID- 20587467 TI - A measure of severe psychological abuse normed on a nationally representative sample of adults. AB - A psychological abuse scale representing truly egregious psychological actions that could occur between adult intimate partners was constructed. To insure that the component behaviors would be viewed as highly problematic, the likely malignant intent of the actions was included in item descriptions. Fourteen categories of psychological abuse were devised as relatively independent forms of destructive behaviors, and, within each category, 3 items were devised to represent increasingly severe psychological actions. A nationally representative sample of adults (N = 614) responding to an online survey rated the perceived severity of the 42 aversive behaviors. Reliability and validity indicators, along with descriptive data, are presented. The ratings of the sample basically established the items as egregious in nature, the categories as distinct from each other, and the items within categories as varying in expected directions in terms of severity. Except for gender, demographics had little effect on participants' ratings. Social desirability and dimensions of attachment showed weak relationships with participants' ratings. PMID- 20587468 TI - Mediators and moderators of change in adjustment following intervention for children exposed to intimate partner violence. AB - Children aged 6 to 12 who were exposed to intimate partner violence (IPV) within the last year participated in an intervention program found to be successful in reducing their internalizing and externalizing behavior problems. However, little is known about factors that may contribute to this efficacy. Both fixed and modifiable risk factors that predicted change in children's adjustment after the intervention were identified and tested. There was a significant relationship between the extent of exposure to IPV, gender, change in mothers' mental health, and change in child adjustment. Among fixed factors, length of exposure to violence was found to moderate the relationship between the amount of the child's and mother's participation in the intervention and change in child adjustment, specifically internalizing behavioral problems. Among the modifiable risk factors, change in mother's mental health, specifically symptoms of posttraumatic stress, was found to mediate the relationship between the amount of intervention participation and change in child adjustment. These findings can be used to inform and enhance evidence-based clinical services for children exposed to IPV. PMID- 20587469 TI - Sleep loss and partner violence victimization. AB - Intimate partner violence victimization has been associated with serious health problems among women, including many disorders that involve sleep disturbances. However, there has been only limited examination of sleep duration among women with victimization experiences. A total of 756 women with a domestic violence order (DVO) against a male intimate partner were interviewed about their health, mental health, substance use, and partner violence victimization. Face-to-face interviews were conducted from February 2001 to November 2003 for data collection in three rural and one urban county representing different jurisdictional settings. Because the current analyses focused on understanding intimate partner victimization in the past year and associations with sleep disturbance, 147 participants were excluded for reporting a relationship with the DVO partner for less than 6 months in the past year. The final sample for this article was 609. The women reported an average of a little above 5.5 hours of sleep per night. For women in the current study, significant predictors of sleep disturbance included race, number of children, number of other symptoms of depression in the past 2 weeks excluding sleep criteria, number of other symptoms of PTSD in the past 2 weeks excluding sleep criteria, number of chronic physical health problems, and severity of physical violence by the DVO partner in the past year. Addressing short sleep duration among partner victims in health care settings might enhance safety planning and prevent the development of health/mental health problems that can arise from victimization. PMID- 20587470 TI - Male social workers working with men who batter: dilemmas in gender identity. AB - Research into the impact of dealing with intimate partner violence has focused mainly on women who treated victims. The present article explores the interaction between male social workers and battering men. The sample included 15 male social workers who worked with battering men in social services. Data collection was performed through semistructured interviews. The main theme emerging from the interviews describes the reconstruction and renegotiation of the worker's professional and personal self in light of his experiences with violent clients. Two major motifs describing their experience emerged: The first is self-doubt arising from adopting a broad definition of violence, thus creating increased sensitization to and inclusion of a wide range of behaviors under the term violence . The second motif is related to compromising with reality by renegotiating their identity as aggressive, at times, but not violent. Findings were discussed in the light of the constructionist perspective. PMID- 20587471 TI - Intimate partner violence within law enforcement families. AB - Using data from the Baltimore Police Stress and Domestic Violence study, the authors examined how exposure to stressful events on the job affects law enforcement employees' physical aggression toward domestic partners, evaluating the role of negative emotions and authoritarian spillover in mediating the impact of such task-related stress. The authors consulted general strain theory and angry aggression theory to explain domestic violence in police families. Significant positive effects on physical aggression toward an intimate partner were found for variables measuring authoritarian spillover and negative emotions. However, these effects were different for different gender and racial groups. PMID- 20587472 TI - Unintended pregnancy and intimate partner violence before and during pregnancy among Latina women in Los Angeles, California. AB - The purpose of this paper was to examine the relationship between unintended pregnancy and intimate partner violence (IPV) before and during pregnancy among Latinas. A cross-sectional interview measuring pregnancy intent, IPV, and acculturation, using the Acculturation Rating Scale for Mexican Americans (ARSMA II), was conducted among Latina women in their 2(nd) or 3(rd) trimester of pregnancy at clinics in Los Angeles (n = 313). Overall, 44% of women reported an unintended pregnancy. The prevalence of physical (any) and emotional (only) abuse 12 months before pregnancy was 11% and 22%, respectively. Although both types of IPV decreased during pregnancy (10% and 19%, respectively), most reports of physical IPV during pregnancy (53%) were among women who did not report physical abuse before pregnancy. After adjusting for other factors, physical IPV before pregnancy was not associated with unintended pregnancy (adjusted OR = 0.92; 95% CI = 0.40, 2.16). The prevalence of unintended pregnancy was highest (76%) among highly acculturated Latinas. However, when an unintended pregnancy occurred among less acculturated Latinas, who comprised the majority of the sample (n = 270), it was associated with greater risk of physical IPV during pregnancy (unadjusted OR = 2.57; 95% CI = 1.06, 6.23); although the confidence interval included one after adjusting for other factors (adjusted OR = 2.79; 95% CI = 0.98, 7.92). An unintended pregnancy may have a unique impact on relationships in the context of Latino culture, where family and pregnancy are highly valued. Pregnancy often creates an opportunity for providers to discuss issues related to abuse and family planning with women who do not regularly access care. The results from this study may be used to increase the cultural sensitivity with which violence and reproductive health are addressed among the diverse population of Latinas when they connect with prenatal services. PMID- 20587473 TI - Threats and acts of intimate partner violence reported by users at Norwegian women's shelters. AB - Women (n = 87) at women's shelters in Norway, a country of high welfare and gender equality, reported a multitude of severe threats and actual acts of physical, sexual and psychological violence. An individual threatening to kill his partner represented a significant increased risk for experiencing serious acts of violence, especially when the threats were repeated. A self-administered questionnaire was sent to all the women's shelters. Experiences of violence were measured by The Severity of Violence against Women Scale (SVAWS) and the Psychological Maltreatment of Women Index (PMWI). PMID- 20587474 TI - Adult attachment and male aggression in couple relationships: the demand-withdraw communication pattern and relationship satisfaction as mediators. AB - This study examines men's domestic aggression as a function of attachment insecurities, considering the mediating roles of the demand-withdraw communication pattern and relationship satisfaction. The sample included 55 Canadian men undergoing counseling for relationship difficulties including aggression. The men completed questionnaires assessing physical and psychological aggression, the two dimensions of attachment insecurity (anxiety over abandonment and avoidance of intimacy), the demand-withdraw communication pattern, relationship satisfaction, and social desirability (a control measure). As predicted, there was an association between attachment anxiety and aggression (both physical and psychological), which was mediated by the man demands/woman withdraws (MD/WW) pattern (as reported by the men). There was no evidence of mediation by the woman demands/man withdraws pattern, as reported by the men. Relationship satisfaction mediated the association between attachment anxiety and psychological (but not physical) aggression, but did not mediate the link between avoidance and aggression (physical or psychological). Limitations and clinical implications are discussed. PMID- 20587475 TI - Dating violence and substance use among ethnically diverse adolescents. AB - Teen dating violence is a serious public health concern with numerous and long lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the association between dating violence victimization and the use of a variety of licit and illicit substances among 1,565 ethnically diverse and economically disadvantaged high school students in southeast Texas. Past year dating violence victimization was reported by 14.1% of boys and 11.3% of girls. Compared to their nonabused counterparts, youth who experienced dating violence were more likely to smoke cigarettes, drink alcohol, binge drink alcohol, sniff glue to get high, use marijuana, use ecstasy, use Vicodin, and use Xanax. However, with the exception of alcohol and cigarettes, all substances were reduced to nonsignificance in multivariate analyses. No differences were found in the rate of dating violence between African American, White, and Hispanic adolescents. PMID- 20587476 TI - The meaning of collective terrorist threat: understanding the subjective causes of terrorism reduces its negative psychological impact. AB - This article hypothesized that the possibility to construct intellectual meaning of a terrorist attack (i.e., whether participants can cognitively understand why the perpetrators did their crime) reduces the negative psychological consequences typically associated with increased terrorist threat. Concretely, the authors investigated the effect of intellectual meaning (induced by providing additional information about potential economic, cultural, and historical reasons for the terrorist attack) on perceived terrorist threat and associated emotional well being. Study 1 revealed that pictures of terrorist attacks elicited less experienced terrorist threat when they were presented with background information about the terrorists' motives (meaning provided) rather than without additional background information (no meaning provided). Study 2 replicated this effect with a different manipulation of terrorist threat (i.e., newspaper article) and clarified the underlying psychological process: Participants in the high terror salience condition with meaning provided experienced less terrorist threat and thus more emotional well-being in the face of crisis than participants in the high terror salience condition without meaning provided. Theoretical and practical implications in the context of psychological health and mass media effects are discussed. PMID- 20587477 TI - Domestic violence and longitudinal associations with children's physiological regulation abilities. AB - The present study examined the impact of domestic violence (DV) on children's emotion regulation abilities measured via baseline vagal tone (VT). Specifically, the authors examined the relationship between DV exposure and children's regulatory functioning over time, investigating whether DV exposure was related to the trajectory of children's physiological regulatory abilities from the preschool period to middle childhood. Covariates, including marital dissatisfaction and conduct-problem status, along with potential gender differences, were examined. Though all children increased in baseline VT from Time 1 to Time 2, children exposed to DV displayed less increase in baseline VT over time as compared to nonexposed children. Results in terms of the long-term outcomes of DV on children and implications for interventions were taken into consideration and discussed in the article. PMID- 20587478 TI - Association of violence against partner and former victim experiences: a sample of clients voluntarily attending therapy. AB - The authors addressed the associations between childhood and adolescence victimization and partner violence in adulthood. Data were collected on 480 men voluntarily attending therapy with a semistructured interview that assessed (a) violent behavior, categorized as physical violence, physical controlling behavior, property violence, psychologically controlling behavior, psychological degradation, indirect aggression, or sexual violence and (b) victim experiences during childhood or adolescence, categorized as physical abuse, psychological abuse, sexual abuse, or exposure to violence between family members. Prior victim experiences of family violence were reported by 60% of participants. Regression analyses showed that past victim experiences, especially physical abuse, was associated with adult violence (p < .05). Specifically, physical abuse was associated with psychologically controlling behavior (p < .05) and sexual abuse with sexual violence (p < .05). PMID- 20587479 TI - Psychometric properties of an intimate partner violence tool for health care students. AB - Health care professionals have acknowledged intimate partner violence (IPV) as a highly prevalent public health problem necessitating the creation of standardized education programs, survey tools, and well-defined outcome measures. Testing and evaluation of these measures, however, has been limited to specific populations of health care professionals. In 2007 and 2008, psychometric properties of the Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS) were adapted, tested, and evaluated on a group of medicine, nursing, social work, and dentistry students during their last semester of college. The adapted instrument demonstrated high reliability within some IPV constructs, and six of the eight scales described in the original PREMIS were identified. Three scales presented a Cronbach's alpha >= .70, demonstrating acceptable reliability, and a new scale, IPV Screening, was also identified that showed good reliability (alpha = .74). The adapted instrument showed good stability of psychometric properties in the student population and generally good correlation within several measures. PMID- 20587480 TI - Contribution of intracranial vertebral artery asymmetry to vestibular neuropathy. AB - OBJECTIVES: To test the hypothesis that vertebral artery hypoplasia (VAH) may affect the lateralisation of vestibular neuropathy (VN), probably through haemodynamic effect on the vestibular labyrinth. METHODS: 69 patients with unilateral VN were examined with a magnetic resonance angiographic (MRA) and caloric test. 50 healthy subjects served as controls. The diagnosis of intracranial VAH was based on MRA if <0.22 cm in VA diameter and a diameter asymmetry index >40%. The authors then correlated the canal paretic side with the VAH side. RESULTS: MRA study revealed 29 VAH (right/left: 23/6) in VN subjects and six VAH in controls (right/left: 5/1). The RR of VAH in VN subjects compared with controls was elevated (RR=2.2; 95% CI 1.8 to 2.8). There was a high accordance rate between the side of VAH and VN. Among 29 patients with unilateral VAH, 65.5% (N=19) had an ipsilateral VN, in which left VAH showed a higher accordance rate (83.3%) than the right side (60.9%). VN subjects with vascular risk factors also had a higher VAH accordance rate (81%) than those without (25%). CONCLUSIONS: VAH may serve as a regional haemodynamic negative contributor and impede blood supply to the ipsilateral vestibular labyrinth, contributing to the development of VN, which could be enhanced by atherosclerotic risk factors and the left-sided location. PMID- 20587481 TI - A comparison of neuropsychiatric and cognitive profiles in delirium, dementia, comorbid delirium-dementia and cognitively intact controls. AB - PURPOSE: Delirium and dementia have overlapping features that complicate differential diagnosis. Delirium symptoms overshadow dementia symptoms when they co-occur, but delirium phenomenology in comorbid cases has not been compared to both conditions alone. METHODS: Consecutive adults with DSM-IV delirium, dementia, comorbid delirium-dementia and cognitively intact controls were assessed using the Revised Delirium Rating Scale (DRS-R98) and Cognitive Test for Delirium (CTD). RESULTS: Delirium and comorbid delirium-dementia groups had comparable DRS-R98 and CTD total scores, which were greater than in dementia or control groups. On the DRS-R98, multiple non-cognitive symptoms, inattention and disorientation were more severe in delirium groups compared with dementia-alone. Patients with dementia differed from both delirium groups on the CTD test of attention. Spatial span backwards was significantly lower in all patients with cognitive impairment (delirium, comorbid delirium-dementia, dementia alone) compared to controls, whereas spatial span forwards distinguished delirium groups from dementia. CONCLUSIONS: Delirium phenomenology is similar with or without comorbid dementia. A wide range of neuropsychiatric symptoms distinguish delirium from dementia. Spatial span forward is disproportionately diminished in delirium suggesting usefulness as a differentiating screening test. PMID- 20587482 TI - Neurological picture. Repetitive internal carotid artery compression of the hyoid: a new mechanism of golfer's stroke? PMID- 20587483 TI - Transient epileptic amnesia: deja vu heralding recovery of lost memories. PMID- 20587485 TI - Fasciculation-cramp syndrome preceding anterior horn cell disease: an intermediate syndrome? AB - Cramp-fasciculation syndrome (cramp-FS) is an ill-defined condition with uncertain clinical limits. The authors studied a 55-year-old man with progressively more severe, widespread fasciculations and cramps during a 6-year period. Mild progressive lower motor neuron loss, shown by motor unit number and multi-motor unit potential (MUP) analysis, developed during the 4 years after onset, which stabilised during a further 2-year follow-up. Cramp-FS is generally a benign syndrome, probably with several causations. Our patient developed a limited form of anterior horn cell degeneration perhaps representing a syndrome transitional with amyotrophic lateral sclerosis. Cramp-FS merits more detailed study. PMID- 20587484 TI - Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy. AB - BACKGROUND: Different preparations of intravenous immunoglobulin (IVIg) are considered to have comparable clinical efficacy but this has never been formally investigated. Some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report that some IVIg brands are more effective than others. A liquid IVIg preparation is more user friendly and potentially can be infused at a faster rate. OBJECTIVES: The primary objective was to compare the efficacy of two different IVIg brands in CIDP. The secondary objective was to compare their safety. METHODS: This was an investigator-initiated multi-centre randomised controlled double-blind trial. Twenty-seven patients with active but stable CIDP treated with their individual stable IVIg (Gammagard S/D) maintenance dose and interval were randomised to receive four infusions of freeze-dried 5% IVIg (Gammagard S/D) or the new liquid 10% IVIg (Kiovig). The overall disability sum score (ODSS) was used as the primary outcome scale. The equivalence margin was defined as a difference of <=1 point in mean DeltaODSS between treatment groups. Main secondary outcome scales were the MRC sum score and the Vigorimeter. RESULTS: Repeated measurements analysis of variance, adjusted for baseline ODSS, showed a clinically insignificant treatment difference of 0.004 (95% CI -0.4 to 0.4). We also found no significant differences in any of the other outcome measures. Besides a lower occurrence of cold shivers in patients randomised to Kiovig (p=0.03), no significant differences were found in the occurrence of adverse events. CONCLUSIONS: This trial demonstrated equal clinical efficacy between a freeze-dried and a liquid IVIg preparation for maintenance treatment of CIDP. PMID- 20587486 TI - Long-term outcome of canal paresis of a vascular cause. AB - There have been several reports on the progress of the caloric response of vestibular neuritis, but little is known about the recovery of canal paresis (CP) of a vascular cause. This study found that the caloric response normalised in 20 (67%) of 30 patients with CP associated with posterior circulation ischaemic stroke who were followed for at least 1 year (mean, 42.5 months; range, 14-85 months). The most commonly infarcted territory on brain MRI associated with CP was in the distribution of the anterior inferior cerebellar artery (26/30, 87%). None of the patients who were followed for >5 years after the onset of vertigo showed persistent CP. Residual dizziness did not differ significantly between patients with or without CP at the final follow-up. These findings suggest that CP associated with posterior circulation ischaemic stroke often has a good long term outcome. Following patients for at least 5 years increases the likelihood of normalisation of the vestibular response to caloric stimulation. PMID- 20587487 TI - Richter's syndrome of the brain and the spinal cord. PMID- 20587488 TI - Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease. AB - OBJECTIVE: To report the rare but distinct clinical and neuropathological phenotype of non-familial, rapidly progressive parkinsonism and dementia associated with frontotemporal lobar degeneration with motor neuron disease (FTLD MND). METHODS: Subjects included two 70-year-old women presenting with rapidly progressive severe postural instability, axial-predominant parkinsonism, oculomotor dysfunction and frontal-predominant dementia with language impairment and pseudobulbar palsy. One had diffuse weakness without signs of lower motor neuron disease. Post-mortem evaluations included immunohistochemistry with antiphospho-TAR DNA-binding protein 43 (TDP-43) and genetic analysis of the TARDBP and PGRN genes. RESULTS: Subjects died within 14 months from symptom onset. TDP-43-positive neuronal intracytoplasmic inclusions were prominent in the primary motor cortex, granule cell layer of the hippocampus, and several cranial and spinal cord nuclei. TDP-43 globular glial inclusions (GGI) were identified in one case. There were no mutations in PGRN or TARDBP genes. CONCLUSIONS: FTLD-MND due to TDP-43-proteinopathy should be considered in patients with rapidly progressive parkinsonism and dementia phenotype, especially when aphasia and/or weakness are also present. PMID- 20587490 TI - Late-onset Boucher-Neuhauser Syndrome (late BNS) associated with white-matter changes: a report of two cases and review of literature. AB - Boucher-Neuhauser syndrome (BNS) is rare autosomal recessive disease, characterised by cerebellar ataxia, hypogonadotropic hypogonadism and chorio retinal degeneration. The authors report a family (brother, 22 years and sister 24 years) with late-onset BNS (>10 years). They had subnormal intelligence; the cerebellar ataxia was progressive over 2 years with early functional dependence. Puberty was attained in a brother with testosterone injections, while the girl had primary amenorrhoea. There were no associated visual complaints. They both had diffuse periventricular white-matter hyperintensities in cerebral cortex and diffuse cerebellar atrophy in the MRI. PMID- 20587489 TI - Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with "normal" serum B12 levels. AB - Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 MUg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible. PMID- 20587491 TI - Neurological picture. Asymtomatic rete mirabile in carotid and vertebral circulation systems. PMID- 20587492 TI - The different infarct patterns between adulthood-onset and childhood-onset moyamoya disease. AB - BACKGROUND AND PURPOSE: The pattern of infarctions based on the findings of diffusion-weighted image was assessed, and it was also investigated whether there are any age-specific differences in patients with moyamoya disease (MMD). METHODS: The subjects were 66 consecutive patients with MMD who had an acute cerebral infarction. Each ischaemic lesion was categorised into one of seven patterns (gyral, atypical territorial, honeycomb, classic territorial, multiple dot, borderzone, deep lacunar) based on diffusion-weighted image findings. The patterns were compared between adulthood-onset MMD (A-MMD, >=20 years old, 34 patients) and childhood/adolescent-onset MMD (C-MMD, <20 years old, 32 patients) according to their ages of infarct presentation. RESULTS: A total of 91 infarct patterns were observed from 66 patients. The gyral, atypical territorial, and honeycomb patterns, which are not usually seen in conventional stroke patients, were common in MMD (68.1%). Among all patterns, a gyral pattern was most common (40/91, 44.0%). Borderzone and deep lacunar patterns were infrequent. Gyral and borderzone patterns were more frequently seen in the C-MMD group, whereas a honeycomb pattern was not seen in young patients. Honeycomb pattern was more common at advanced vascular stages. Infarctions confined to the cortex were more common in the C-MMD group (26/32, 75.0%) than in A-MMD patients (14/34, 41.2%). CONCLUSIONS: Moyamoya disease showed various characteristic and age-specific infarct patterns. Different infarct patterns between the A-MMD and C-MMD groups may be associated with age-specific vulnerability of the brain to ischaemia, stage of arteriopathy or changes of abnormal collateral pathways. PMID- 20587493 TI - Detecting deficits of sustained visual attention in delirium. AB - BACKGROUND: Inattention is a core clinical feature of delirium and yet the particular aspects of attentional impairment associated with this feature are poorly understood. Objective methods for assessing inattention are also lacking. A new set of computerised tests of attentional deficits designed for use in patients with delirium have been developed. Test performances in patients with delirium, dementia and cognitively normal controls are compared. METHODS: Eight novel tasks measuring sustained visual attention were administered to 20 older patients with delirium using the Edinburgh Delirium Test Box, a purpose built, computerised neuropsychological testing device. Comparison groups of 18 patients with Alzheimer's dementia and 20 cognitively normal patients of similar age were also assessed. Delirium was diagnosed using the Confusion Assessment Method. General cognitive impairment was measured using the Mini-Mental State Examination. RESULTS: Patients with delirium had significantly lower scores than both comparison groups on all sustained attention tasks (p values from 0.003 to <0.001). Performance of the dementia patients generally did not differ from the cognitively normal group. Receiver operating characteristic analyses indicated that all tasks showed good or excellent accuracy for discriminating between delirium and dementia (AUC values 0.80-0.94), and between delirium and cognitively normal (AUC values 0.89-0.99) patients. CONCLUSIONS: Patients with delirium showed marked deficits in sustained visual attention, as measured by objective neuropsychological testing. These attentional deficits were mainly mild or absent in patients with dementia and in cognitively normal controls. Objective testing of sustained visual attention has promising utility in detecting delirium, and in discriminating delirium from dementia. PMID- 20587494 TI - Spinocerebellar ataxia type 17 associated with an expansion of 42 glutamine residues in TATA-box binding protein gene. AB - BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is >=43. OBJECTIVE: To investigate the minimal CAG/CAA expansion within the TBP in SCA17. RESULTS: 285 patients with autosomal-dominant ataxia were examined, and abnormal or borderline expansions of CAG/CAA within TBP in eight cases were found. Of those, four patients from three families had exactly 42 CAG/CAA trinucleotides, that is, one codon less than the currently accepted critical threshold of 43. The four patients presented with a relatively benign phenotype. All had dysdiadochokinesia and dysarthria. Mild gait ataxia was observed in three of the four patients. CONCLUSION: The reference definition of at least 43 CAG/CAA codons for pathological SCA17 alleles should be lowered to 42. PMID- 20587495 TI - Relationship between radiological characteristics and combined 1p and 19q deletion in World Health Organization grade III oligodendroglial tumours. AB - OBJECTIVE: The radiological characteristics of World Health Organization grade III oligodendroglial tumours in relation to chromosome 1p and 19q deletions were analysed. METHODS: 56 patients recently diagnosed with anaplastic oligodendroglioma (AO, n=49) or anaplastic oligoastrocytoma (AOA, n=7) were studied. Their preoperative magnetic resonance images were examined. Deletions of chromosome 1p and 19q were determined using the fluorescence in situ hybridisation method. Both 1p and 19q chromosomes had deletions (1p19q codeletion) in 39 patients (36 AO and 3 AOA). RESULTS: Tumors associated with the 1p19q codeletion were predominantly located in the frontal lobe (p=0.044). The magnetic resonance image characteristics of indistinct tumour borders (p=0.005 on T1, p=0.036 on T2) and a heterogeneous intratumoural signal intensity (p=0.033 on T1, p=0.041 on T2) were significantly correlated with the 1p19q codeletion. Analysis of patient survival showed those with the 1p19q-co-deleted tumours survived significantly longer than those lacking the 1p19q codeletion (p=0.042). The presence of a heterogeneous signal intensity in T2-weighted images, a characteristic significantly related to the 1p19q codeletion, indicated a favourable prognosis for patients' survival (HR; 0.125, 95% CI, 0.016 to 0.963, p=0.046) based on multivariate analysis. CONCLUSION: A relationship between radiological characteristics and molecular signatures in AO/AOAs was shown. It is believed that radiological characteristics have prognostic value as a surrogate marker for molecular characteristics. PMID- 20587496 TI - Early-onset Charcot-Marie-Tooth patients with mitofusin 2 mutations and brain involvement. AB - Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot-Marie-Tooth disease (CMT). A prospective brain MRI study was performed on 18 early-onset CMT patients with MFN2 mutations, and a high frequency (39%) of brain abnormalities was found. Early-onset patients showed multiple scattered or confluent brain lesions that involved gray matter as well as white matter. Patterns of brain involvement in early-onset patients differed from those of late-onset patients and other hereditary peripheral neuropathies. In addition, one CMT patient demonstrated a brain lesion before the development of peripheral neuropathy. PMID- 20587497 TI - Coping with amyotrophic lateral sclerosis: an integrative view. AB - OBJECTIVES: To identify predictors of psychosocial adjustment to motor neurone disease. METHODS: A total of 27 individuals with a confirmed diagnosis of amyotrophic lateral sclerosis (ALS) participated in the study. The ALS functional rating scale mean score indicated a high physical impairment of the sample. Months since diagnosis varied between 4 and 129 (median 36). Adjustment outcomes were severity of depressive symptoms and individual quality of life (QoL). Predictors included social support, cognitive appraisal, coping strategies and illness parameters. RESULTS: Multiple regression analysis revealed that approximately 60% of the variance of depression and QoL were accounted for by social support, coping strategies and cognitive appraisal. The degree of physical impairment did not explain any variance of the adjustment outcomes. The best predictors for the severity of depressive symptoms were perceived social support and appraisal of coping potential (internal locus of control) and for individual QoL perceived social support. CONCLUSIONS: The focus on medical issues in treatment of ALS is not sufficient. A palliative approach to ALS must equally imply advice with regards to adequate coping strategies, provide the adequate amount of disease- and support-related information at any one time, and encourage patients to seek social support. Sufficient medication and psychotherapy has to be provided for those patients who show depressive symptoms or disorder. PMID- 20587498 TI - Are subjects with spondylotic cervical cord encroachment at increased risk of cervical spinal cord injury after minor trauma? AB - The aim of the study was to analyse the risk of symptomatic myelopathy after minor trauma in patients with asymptomatic spondylotic cervical spinal cord encroachment (ASCCE). In a cohort of 199 patients with ASCCE, previously followed prospectively in a study investigating progression into symptomatic myelopathy, the authors looked retrospectively for traumatic episodes that may have involved injury to the cervical spine. A questionnaire and data file analysis were employed to highlight whatever hypothetical relationship might emerge with the development of symptomatic myelopathy. Fourteen traumatic episodes in the course of a follow-up of 44 months (median) were recorded in our group (who had been instructed to avoid risky activities), with no significant association with the development of symptomatic myelopathy (found in 45 cases). Only three minor traumatic events without fracture of the cervical spine were found among the symptomatic myelopathy cases, with no chronological relationship between trauma and myelopathy. Furthermore, 56 traumatic spinal cord events were found before the diagnosis of cervical cord encroachment was established, with no correlation to either type of compression (discogenic vs osteophytic). In conclusion, the risk of spinal cord injury after minor trauma of the cervical spine in patients with ASCCE appeared to be low in our cohort provided risky activities in these individuals are restricted. Implementation of preventive surgical decompression surgery into clinical practice in these individuals should be postponed until better-designed studies provide proof enough for it to take precedence over a conservative approach. PMID- 20587499 TI - Road blocks on paleogenomes--polymerase extension profiling reveals the frequency of blocking lesions in ancient DNA. AB - Although the last few years have seen great progress in DNA sequence retrieval from fossil specimens, some of the characteristics of ancient DNA remain poorly understood. This is particularly true for blocking lesions, i.e. chemical alterations that cannot be bypassed by DNA polymerases and thus prevent amplification and subsequent sequencing of affected molecules. Some studies have concluded that the vast majority of ancient DNA molecules carry blocking lesions, suggesting that the removal, repair or bypass of blocking lesions might dramatically increase both the time depth and geographical range of specimens available for ancient DNA analysis. However, previous studies used very indirect detection methods that did not provide conclusive estimates on the frequency of blocking lesions in endogenous ancient DNA. We developed a new method, polymerase extension profiling (PEP), that directly reveals occurrences of polymerase stalling on DNA templates. By sequencing thousands of single primer extension products using PEP methodology, we have for the first time directly identified blocking lesions in ancient DNA on a single molecule level. Although we found clear evidence for blocking lesions in three out of four ancient samples, no more than 40% of the molecules were affected in any of the samples, indicating that such modifications are far less frequent in ancient DNA than previously thought. PMID- 20587500 TI - When simple sequence comparison fails: the cryptic case of the shared domains of the bacterial replication initiation proteins DnaB and DnaD. AB - DnaD and DnaB are essential DNA-replication-initiation proteins in low-G+C content Gram-positive bacteria. Here we use sensitive Hidden Markov Model-based techniques to show that the DnaB and DnaD proteins share a common structure that is evident across all their structural domains, termed DDBH1 and DDBH2 (DnaD DnaB Homology 1 and 2). Despite strong sequence divergence, many of the DNA-binding and oligomerization properties of these domains have been conserved. Although eluding simple sequence comparisons, the DDBH2 domains share the only strong sequence motif; an extremely highly conserved YxxxIxxxW sequence that contributes to DNA binding. Sequence alignments of DnaD alone fail to identify another key part of the DNA-binding module, since it includes a poorly conserved sequence, a solvent-exposed and somewhat unstable helix and a mobile segment. We show by NMR, in vitro mutagenesis and in vivo complementation experiments that the DNA-binding module of Bacillus subtilis DnaD comprises the YxxxIxxxW motif, the unstable helix and a portion of the mobile region, the latter two being essential for viability. These structural insights lead us to a re-evaluation of the oligomerization and DNA-binding properties of the DnaD and DnaB proteins. PMID- 20587501 TI - BspRI restriction endonuclease: cloning, expression in Escherichia coli and sequential cleavage mechanism. AB - The GGCC-specific restriction endonuclease BspRI is one of the few Type IIP restriction endonucleases, which were suggested to be a monomer. Amino acid sequence information obtained by Edman sequencing and mass spectrometry analysis was used to clone the gene encoding BspRI. The bspRIR gene is located adjacently to the gene of the cognate modification methyltransferase and encodes a 304 aa protein. Expression of the bspRIR gene in Escherichia coli was dependent on the replacement of the native TTG initiation codon with an ATG codon, explaining previous failures in cloning the gene using functional selection. A plasmid containing a single BspRI recognition site was used to analyze kinetically nicking and second-strand cleavage under steady-state conditions. Cleavage of the supercoiled plasmid went through a relaxed intermediate indicating sequential hydrolysis of the two strands. Results of the kinetic analysis of the first- and second-strand cleavage are consistent with cutting the double-stranded substrate site in two independent binding events. A database search identified eight putative restriction-modification systems in which the predicted endonucleases as well as the methyltransferases share high sequence similarity with the corresponding protein of the BspRI system. BspRI and the related putative restriction endonucleases belong to the PD-(D/E)XK nuclease superfamily. PMID- 20587502 TI - Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer. AB - Tyrosine kinase (TK) fusions are attractive drug targets in cancers. However, rapid identification of these lesions has been hampered by experimental limitations. Our in silico analysis of known cancer-derived TK fusions revealed that most breakpoints occur within a defined region upstream of a conserved GXGXXG kinase motif. We therefore designed a novel DNA-based targeted sequencing approach to screen systematically for fusions within the 90 human TKs; it should detect 92% of known TK fusions. We deliberately paired 'in-solution' DNA capture with 454 sequencing to minimize starting material requirements, take advantage of long sequence reads, and facilitate mapping of fusions. To validate this platform, we analyzed genomic DNA from thyroid cancer cells (TPC-1) and leukemia cells (KG-1) with fusions known only at the mRNA level. We readily identified for the first time the genomic fusion sequences of CCDC6-RET in TPC-1 cells and FGFR1OP2-FGFR1 in KG-1 cells. These data demonstrate the feasibility of this approach to identify TK fusions across multiple human cancers in a high throughput, unbiased manner. This method is distinct from other similar efforts, because it focuses specifically on targets with therapeutic potential, uses only 1.5 ug of DNA, and circumvents the need for complex computational sequence analysis. PMID- 20587503 TI - Relative quantitation of transfer RNAs using liquid chromatography mass spectrometry and signature digestion products. AB - Transfer ribonucleic acids (tRNAs) are challenging to identify and quantify from unseparated mixtures. Our lab previously developed the signature digestion approach for identifying tRNAs without specific separation. Here we describe the combination of relative quantification via enzyme-mediated isotope labeling with this signature digestion approach for the relative quantification of tRNAs. These quantitative signature digestion products were characterized using liquid chromatography mass spectrometry (LC-MS), and we find that up to 5-fold changes in tRNA abundance can be quantified from sub-microgram amounts of total tRNA. Quantitative tRNA signature digestion products must (i) incorporate an isotopic label during enzymatic digestion; (ii) have no m/z interferences from other signature digestion products in the sample and (iii) yield a linear response during LC-MS analysis. Under these experimental conditions, the RNase T1, A and U2 signature digestion products that potentially could be used for the relative quantification of Escherichia coli tRNAs were identified, and the linearity and sequence identify of RNase T1 signature digestion products were experimentally confirmed. These RNase T1 quantitative signature digestion products were then used in proof-of-principle experiments to quantify changes arising due to different culturing media to 17 tRNA families. This method enables new experiments where information regarding tRNA identity and changes in abundance are desired. PMID- 20587504 TI - Single molecule analysis of combinatorial splicing. AB - Alternative splicing creates diverse mRNA isoforms from single genes and thereby enhances complexity of transcript structure and of gene function. We describe a method called spliceotyping, which translates combinatorial mRNA splicing patterns along transcripts into a library of binary strings of nucleic acid tags that encode the exon composition of individual mRNA molecules. The exon inclusion pattern of each analyzed transcript is thus represented as binary data, and the abundance of different splice variants is registered by counts of individual molecules. The technique is illustrated in a model experiment by analyzing the splicing patterns of the adenovirus early 1A gene and the beta actin reference transcript. The method permits many genes to be analyzed in parallel and it will be valuable for elucidating the complex effects of combinatorial splicing. PMID- 20587505 TI - Paracelsus and formaldehyde 2010: the dose to the target organ makes the poison. PMID- 20587506 TI - Cardiac electrophysiological effects of nitric oxide. AB - Nitric oxide (NO) synthetized by essentially all cardiac cell types plays a key role in the regulation of cardiac function. Recent evidence shows that NO modulates the activity of cardiac ion channels implicated in the genesis of the cardiac action potential and exerts anti-arrhythmic properties under some circumstances. We review the effects of NO on cardiac ion channels and the signalling pathways, including cGMP-dependent (protein kinase G and cGMP regulated phosphodiesterases) and cGMP-independent mechanisms (S-nitrosylation and direct effects on G proteins) and finally the role of NO in the genesis of cardiac arrhythmias during ischemia-reperfusion, heart failure, long QT syndrome, atrial fibrillation, and sudden cardiac death. PMID- 20587507 TI - Time to study another variant of endothelial progenitor cells? PMID- 20587508 TI - Calmodulin: a gatekeeper for ryanodine receptor function in the myocardium. PMID- 20587509 TI - Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study. AB - BACKGROUND: this study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. PATIENTS AND METHODS: data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. RESULTS: sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. CONCLUSIONS: combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma. PMID- 20587511 TI - Merkel cell carcinoma, chronic lymphocytic leukemia and other lymphoproliferative disorders: an old bond with possible new viral ties. AB - Merkel cell carcinoma (MCC) is a rare and aggressive skin tumor. The link between tumorigenesis and immunosuppression is well known and the increased prevalence of MCC in human immunodeficiency virus carriers and organ transplant recipients and in patients with hemato-oncological neoplasias is now well recognized over the past decade. In this respect, chronic lymphocytic leukemia (CLL) seems to be the most frequent neoplasia associated with the development of MCC. Very recently, a newly described virus, the Merkel cell polyomavirus, was found in ~80% of MCC tumor samples and is in fact the first member of the polyomavirus family to be associated with human tumors. The virus appears to play a role in the pathogenesis of MCC and may constitute the missing link between immunosuppression and the development of MCC. This review summarizes the current knowledge relating to MCC and its pathogenesis, stressing the link with hematologic neoplasias in general and to CLL in particular. We describe the permissive immunologic environment, which enables the virus-containing tumor cells to survive and proliferate in disorders like CLL. More studies are still needed to confirm this appealing theory in a more convincing manner. PMID- 20587513 TI - Cell-permeable peptide DEPDC1-ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells. AB - Bladder cancer is the second most common genitourinary cancer worldwide, yet its oncogenic origins remain poorly understood. The cancer-testis antigen DEPDC1 was shown recently to contribute to bladder cancer oncogenesis. In this study, we examined the biological functions of DEPDC1 and defined a potential therapeutic strategy to target this molecule. Coimmunoprecipitation and immunocytochemistry revealed that DEPDC1 interacted and colocalized with zinc finger transcription factor ZNF224, a known transcriptional repressor. Inhibiting this interaction with a cell-permeable peptide corresponding to the ZNF224-interacting domain in DEPDC1 induced apoptosis of bladder cancer cells in vitro and in vivo. By inhibiting DEPDC1-ZNF224 complex formation, this peptide triggered transcriptional activation of A20, a potent inhibitor of the NF-kappaB signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis. PMID- 20587510 TI - Prognoses for head and neck cancers in Europe diagnosed in 1995-1999: a population-based study. AB - BACKGROUND: head and neck cancers are a heterogeneous group of malignancies, affecting various sites and subsites, with differing prognoses. The aim of this study was to analyse survival for European head and neck cancer patients in populations covered by population-based cancer registries (CRs), in relation to tumour subsite as prognostic factor. PATIENTS AND METHODS: we analysed 51 912 adult head and neck cancer cases (36 322 mouth-pharynx and 15 590 larynx) diagnosed from 1995 to 1999 and archived by 45 CRs in 20 countries participating in EUROCARE-4. Five-year age-standardised relative survival was estimated for mouth-pharynx and larynx sites by sex and country. Relative survival was modelled to provide estimates of relative excess risks (RERs) of death by country, adjusted for confounding factors. RESULTS: a large but site-variable proportion of tumours were incompletely specified. Five-year age-standardised relative survival was low in Slovakia and high in The Netherlands. Adjustment for subsite reduced RERs of death for most countries; 5-year relative survival increased from 1990-1994 to 1995-1999 for all subsites, while between-country differences in survival narrowed. CONCLUSION: differences in subsite distribution explain a considerable part of the survival differences for head and neck cancers, however, incomplete/inaccurate subsite reporting complicate interpretation. PMID- 20587512 TI - The initial peopling of the Americas: a growing number of founding mitochondrial genomes from Beringia. AB - Pan-American mitochondrial DNA (mtDNA) haplogroup C1 has been recently subdivided into three branches, two of which (C1b and C1c) are characterized by ages and geographical distributions that are indicative of an early arrival from Beringia with Paleo-Indians. In contrast, the estimated ages of C1d--the third subset of C1--looked too young to fit the above scenario. To define the origin of this enigmatic C1 branch, we completely sequenced 63 C1d mitochondrial genomes from a wide range of geographically diverse, mixed, and indigenous American populations. The revised phylogeny not only brings the age of C1d within the range of that of its two sister clades, but reveals that there were two C1d founder genomes for Paleo-Indians. Thus, the recognized maternal founding lineages of Native Americans are at least 15, indicating that the overall number of Beringian or Asian founder mitochondrial genomes will probably increase extensively when all Native American haplogroups reach the same level of phylogenetic and genomic resolution as obtained here for C1d. PMID- 20587514 TI - Mouse models for the p53 R72P polymorphism mimic human phenotypes. AB - The p53 tumor suppressor gene contains a common single nucleotide polymorphism (SNP) that results in either an arginine or proline at position 72 of the p53 protein. This polymorphism affects the apoptotic activity of p53 but the mechanistic basis and physiologic relevance of this phenotypic difference remain unclear. Here, we describe the development of mouse models for the p53 R72P SNP using two different approaches. In both sets of models, the human or humanized p53 proteins are functional as evidenced by the transcriptional induction of p53 target genes in response to DNA damage and the suppression of early lymphomagenesis. Consistent with in vitro studies, mice expressing the 72R variant protein (p53R) have a greater apoptotic response to several stimuli compared with mice expressing the p53P variant. Molecular studies suggest that both transcriptional and nontranscriptional mechanisms may contribute to the differential abilities of the p53 variants to induce apoptosis. Despite a difference in the acute response to UV radiation, no difference in the tumorigenic response to chronic UV exposure was observed between the polymorphic mouse models. These findings suggest that under at least some conditions, the modulation of apoptosis by the R72P polymorphism does not affect the process of carcinogenesis. PMID- 20587516 TI - Translocation of Helicobacter pylori CagA into Human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. AB - Infection by cagA-positive Helicobacter pylori (H. pylori) is strongly associated with gastric carcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. H. pylori translocates the bacterial protein CagA into gastric epithelial cells, and the translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. This in turn raised the possibility that H. pylori is associated with the development of MALT lymphomas during persistent infection by direct interaction with B lymphocytes. In this work, we showed that CagA can be directly translocated into human B lymphoid cells by H. pylori, and the translocated CagA undergoes tyrosine phosphorylation and binds to intracellular SH-2. Meanwhile, the translocated CagA induces activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in human B lymphoid cells, and upregulates the expressions of Bcl-2 and Bcl-X(L), which prevents apoptosis. These results provide the first direct evidence for the role of CagA as a bacterium-derived oncoprotein that acts in human B cells, and further implies that CagA is directly delivered into B cells by H. pylori and is associated with the development of MALT lymphomas. PMID- 20587515 TI - Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer. AB - The expression of several members of the FOX gene family is known to be altered in a variety of cancers. We show that in breast cancer, FOXF1 gene is a target of epigenetic inactivation and that its gene product exhibits tumor-suppressive properties. Loss or downregulation of FOXF1 expression is associated with FOXF1 promoter hypermethylation in breast cancer cell lines and in invasive ductal carcinomas. Methylation of FOXF1 in invasive ductal carcinoma (37.6% of 117 cases) correlated with high tumor grade. Pharmacologic unmasking of epigenetic silencing in breast cancer cells restored FOXF1 expression. Re-expression of FOXF1 in breast cancer cells with epigenetically silenced FOXF1 genes led to G(1) arrest concurrent with or without apoptosis to suppress both in vitro cell growth and in vivo tumor formation. FOXF1-induced G(1) arrest resulted from a blockage at G(1)-S transition of the cell cycle through inhibition of the CDK2-RB-E2F cascade. Small interfering RNA-mediated depletion of FOXF1 in breast cancer cells led to increased DNA re-replication, suggesting that FOXF1 is required for maintaining the stringency of DNA replication and genomic stability. Furthermore, expression profiling of cell cycle regulatory genes showed that abrogation of FOXF1 function resulted in increased expression of E2F-induced genes involved in promoting the progression of S and G(2) phases. Therefore, our studies have identified FOXF1 as a potential tumor suppressor gene that is epigenetically silenced in breast cancer, which plays an essential role in regulating cell cycle progression to maintain genomic stability. PMID- 20587517 TI - STAMP1 is both a proliferative and an antiapoptotic factor in prostate cancer. AB - STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and is deregulated in prostate cancer. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, is unknown. Here, we find that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS-7 cells in vitro; conversely, small interfering RNA-mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth and, at least partially, induced cell cycle arrest. In parallel, there were alterations in cell cycle regulatory gene expression. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. Consistently, LNCaP cells with short hairpin RNA-mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Interestingly, activation of extracellular signal-regulated kinase, which has previously been implicated in prostate cancer progression, was significantly increased on ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly downregulated on STAMP1 knockdown in LNCaP cells. In the normal prostate, STAMP1 protein is localized to the cytosol and the cell membrane of the prostate epithelial cells; furthermore, its expression is increased in prostate cancer compared with normal prostate. Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment. PMID- 20587518 TI - Runx regulation of sphingolipid metabolism and survival signaling. AB - The Runx genes (Runx1, 2, and 3) regulate cell fate in development and can operate as either oncogenes or tumor suppressors in cancer. The oncogenic potential of ectopic Runx expression has been shown in transgenic mice that develop lymphoma in potent synergy with overexpressed Myc, and in established fibroblasts that display altered morphology and increased tumorigenicity. Candidate oncogenic functions of overexpressed Runx genes include resistance to apoptosis in response to intrinsic and extrinsic stresses. In a search for gene targets responsible for this aspect of Runx phenotype, we have identified three key enzymes in sphingolipid metabolism (Sgpp1, Ugcg, and St3gal5/Siat9) as direct targets for Runx transcriptional regulation in a manner consistent with survival and apoptosis resistance. Consistent with these changes in gene expression, mass spectrometric analysis showed that ectopic Runx reduces intracellular long-chain ceramides in NIH3T3 fibroblasts and elevated extracellular sphingosine 1 phosphate. Runx expression also opposed the activation of c-Jun-NH(2)-kinase and p38(MAPK), key mediators of ceramide-induced death, and suppressed the onset of apoptosis in response to exogenous tumor necrosis factor alpha. The survival advantage conferred by ectopic Runx could be partially recapitulated by exogenous sphingosine 1 phosphate and was accompanied by reduced phosphorylation of p38(MAPK). These results reveal a novel link between transcription factor oncogenes and lipid signaling pathways involved in cancer cell survival and chemoresistance. PMID- 20587520 TI - HuR regulates beta-tubulin isotype expression in ovarian cancer. AB - The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III beta-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3' flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival. PMID- 20587519 TI - Nrdp1-mediated regulation of ErbB3 expression by the androgen receptor in androgen-dependent but not castrate-resistant prostate cancer cells. AB - Patients with advanced prostate cancer (PCa) are initially susceptible to androgen withdrawal (AW), but ultimately develop resistance to this therapy (castration-resistant PCa, CRPC). Here, we show that AW can promote CRPC development by increasing the levels of the receptor tyrosine kinase ErbB3 in androgen-dependent PCa, resulting in AW-resistant cell cycle progression and increased androgen receptor (AR) transcriptional activity. CRPC cell lines and human PCa tissue overexpressed ErbB3, whereas downregulation of ErbB3 prevented CRPC cell growth. Investigation of the mechanism by which AW augments ErbB3, using normal prostate-derived pRNS-1-1 cells, and androgen-dependent PCa lines LNCaP, PC346C, and CWR22 mouse xenografts, revealed that the AR suppresses ErbB3 protein levels, whereas AW relieves this suppression, showing for the first time the negative regulation of ErbB3 by AR. We show that AR activation promotes ErbB3 degradation in androgen-dependent cells, and that this effect is mediated by AR dependent transcriptional upregulation of neuregulin receptor degradation protein 1 (Nrdp1), an E3 ubiquitin ligase that targets ErbB3 for degradation but whose role in PCa has not been previously examined. Therefore, AW decreases Nrdp1 expression, promoting ErbB3 protein accumulation, and leading to AR-independent proliferation. However, in CRPC sublines of LNCaP and CWR22, which strongly overexpress the AR, ErbB3 levels remain elevated due to constitutive suppression of Nrdp1, which prevents AR regulation of Nrdp1. Our observations point to a model of CRPC development in which progression of PCa to castration resistance is associated with the inability of AR to transcriptionally regulate Nrdp1, and predict that inhibition of ErbB3 during AW may impair CRPC development. PMID- 20587521 TI - Membrane type 1-matrix metalloproteinase cleaves off the NH2-terminal portion of heparin-binding epidermal growth factor and converts it into a heparin independent growth factor. AB - Epidermal growth factor (EGF) receptors (ErbB) and EGF family members represent promising targets for cancer therapy. Heparin-binding EGF (HB-EGF) is a member of the EGF family and is an important target for therapy in some types of human cancers. Processing of HB-EGF by proprotein convertases, and successively, by ADAM family proteases, generates a soluble growth factor that requires heparin as a cofactor. Although heparin potentiates HB-EGF activity in vitro, it is not clear how the heparin-binding activity of HB-EGF is regulated. Here, we show that membrane type 1-matrix metalloproteinase (MT1-MMP; MMP14), a potent invasion promoting protease, markedly enhances HB-EGF-dependent tumor formation in mice. MT1-MMP additionally cleaves HB-EGF and removes the NH(2)-terminal 20 amino acids that are important for binding heparin. Consequently, the processing of HB-EGF by MT1-MMP converts HB-EGF into a heparin-independent growth factor with enhanced mitogenic activity, and thereby, expression of both proteins costimulates tumor cell growth in vitro and in vivo. The ErbB family of receptors expressed in human gastric carcinoma cells play a role in mediating enhanced HB-EGF activity by MT1 MMP during invasive cell growth in collagen. Thus, we shed light on a new mechanism whereby HB-EGF activity is regulated that should be considered when designing HB-EGF-targeted cancer therapy. PMID- 20587522 TI - Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. AB - Mutations in DKC1, encoding for dyskerin, a pseudouridine synthase that modifies rRNA and regulates telomerase activity, are associated with ribosomal dysfunction and increased cancer susceptibility in the human syndrome, X-linked dyskeratosis congenita (X-DC). In a mouse model for X-DC, impairments in DKC1 function affected the translation of specific mRNAs harboring internal ribosomal entry site (IRES) elements, including the tumor suppressor, p27. However, how this translational deregulation contributes to tumor initiation and progression remains poorly understood. Here, we report that impairment in p27 IRES-mediated translation due to decreased levels of DKC1 activity markedly increases spontaneous pituitary tumorigenesis in p27 heterozygous mice. Using a new bioluminescent mouse model, we monitored p27 translation in vivo and show that p27 IRES-mediated translation is reduced in the pituitary of DKC1 hypomorphic mice (DKC1(m)). Furthermore, we show that DKC1 has a critical role in regulating the assembly of the 48S translational preinitiation complex mediated by the p27 IRES element. An analysis of human tumors identified a novel mutation of DKC1 (DKC1(S485G)) in a human pituitary adenoma. We show that this specific amino acid substitution significantly alters DKC1 stability/pseudouridylation activity, and this correlates with reductions in p27 protein levels. Furthermore, DKC1(S485G) mutation does not alter telomerase RNA levels. Altogether, these findings show that genetic alterations in DKC1 could contribute to tumorigenesis associated with somatic cancers and establish a critical role for DKC1 in tumor suppression, at least in part, through translational control of p27. PMID- 20587524 TI - MicroRNA biogenesis is required for Myc-induced B-cell lymphoma development and survival. AB - Many tumor cells express globally reduced levels of microRNAs (miRNA), suggesting that decreased miRNA expression in premalignant cells contributes to their tumorigenic phenotype. In support of this, Dicer, an RNase III-like enzyme that controls the maturation of miRNA, was recently shown to function as a haploinsufficient tumor suppressor in nonhematopoietic cells. Because the Myc oncoprotein, a critical inducer of B-cell lymphomas, was reported to suppress the expression of multiple miRNAs in lymphoma cells, it was presumed that a deficiency of Dicer and subsequent loss of miRNA maturation would accelerate Myc induced lymphoma development. We report here that, surprisingly, a haploinsufficiency of Dicer in B cells failed to promote B-cell malignancy or accelerate Myc-induced B-cell lymphomagenesis in mice. Moreover, deletion of Dicer in B cells of CD19-cre(+)/Emicro-myc mice significantly inhibited lymphomagenesis, and all lymphomas that did arise in these mice lacked functional Cre expression and retained at least one functional Dicer allele. Uncharacteristically, the lymphomas that frequently developed in the CD19 cre(+)/Dicer(fl/fl)/Emicro-myc mice were of very early precursor B-cell origin, a stage of B-cell development prior to Cre expression. Therefore, loss of Dicer function was not advantageous for lymphomagenesis, but rather, Dicer ablation was strongly selected against during Myc-induced B-cell lymphoma development. Moreover, deletion of Dicer in established B-cell lymphomas resulted in apoptosis, revealing that Dicer is required for B-cell lymphoma survival. Thus, Dicer does not function as a haploinsufficient tumor suppressor in B cells and is required for B-cell lymphoma development and survival. PMID- 20587525 TI - Epigenetic regulation of vitamin D 24-hydroxylase/CYP24A1 in human prostate cancer. AB - Calcitriol, a regulator of calcium homeostasis with antitumor properties, is degraded by the product of the CYP24A1 gene, which is downregulated in human prostate cancer by unknown mechanisms. We found that CYP24A1 expression is inversely correlated with promoter DNA methylation in prostate cancer cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (DAC) activates CYP24A1 expression in prostate cancer cells. In vitro methylation of the CYP24A1 promoter represses its promoter activity. Furthermore, inhibition of histone deacetylases by trichostatin A (TSA) enhances the expression of CYP24A1 in prostate cancer cells. Quantitative chromatin immunoprecipitation-PCR (ChIP qPCR) reveals that specific histone modifications are associated with the CYP24A1 promoter region. Treatment with TSA increases H3K9ac and H3K4me2 and simultaneously decreases H3K9me2 at the CYP24A1 promoter. ChIP-qPCR assay reveals that treatment with DAC and TSA increases the recruitment of vitamin D receptor to the CYP24A1 promoter. Reverse transcriptase-PCR analysis of paired human prostate samples revealed that CYP24A1 expression is downregulated in prostate malignant lesions compared with adjacent histologically benign lesions. Bisulfite pyrosequencing shows that CYP24A1 gene is hypermethylated in malignant lesions compared with matched benign lesions. Our findings indicate that repression of CYP24A1 gene expression in human prostate cancer cells is mediated in part by promoter DNA methylation and repressive histone modifications. PMID- 20587526 TI - Tumor antigen epitopes interpreted by the immune system as self or abnormal-self differentially affect cancer vaccine responses. AB - Epitope selection is an important consideration in the design of cancer vaccines, but factors affecting selection are not fully understood. We compared the immune responses to peptides and glycopeptides from the common human tumor antigen MUC1, a mucin that is coated with O-linked carbohydrates in its variable number of tandem repeats (VNTR) region. MUC1 expressed on tumor cells is characteristically underglycosylated, creating peptide and glycopeptide neoepitopes that are recognized by the immune system. The response to VNTR peptides is weaker in MUC1 transgenic mice (MUC1-Tg mice) than in wild-type (WT) mice, whereas the response to VNTR glycopeptides is equally strong in the two strains. Thus, glycopeptides seem to be recognized as foreign, whereas peptides, although immunogenic, are perceived as self. To explore this further, we generated MUC1 peptide- and glycopeptide-specific T-cell receptor transgenic mice and studied the function of their CD4 T cells when adoptively transferred into MUC1-Tg or WT mice. Peptide specific T-cell precursors were not centrally deleted in MUC1-Tg mice and did not acquire a T regulatory phenotype. However, their response to the cognate peptide was reduced in MUC1-Tg mice compared with WT mice. In contrast, glycopeptide specific CD4 T cells responded equally well in the two hosts and, when simultaneously activated, also enhanced the peptide-specific T-cell responses. Our data show that the immune system differentially recognizes various epitopes of tumor-associated antigens either as self or as foreign, and this controls the strength of antitumor immunity. This represents an important consideration for designing safe and effective cancer vaccines. PMID- 20587527 TI - DNMT3B7, a truncated DNMT3B isoform expressed in human tumors, disrupts embryonic development and accelerates lymphomagenesis. AB - Epigenetic changes are among the most common alterations observed in cancer cells, yet the mechanism by which cancer cells acquire and maintain abnormal DNA methylation patterns is not understood. Cancer cells have an altered distribution of DNA methylation and express aberrant DNA methyltransferase 3B transcripts, which encode truncated proteins, some of which lack the COOH-terminal catalytic domain. To test if a truncated DNMT3B isoform disrupts DNA methylation in vivo, we constructed two lines of transgenic mice expressing DNMT3B7, a truncated DNMT3B isoform commonly found in cancer cells. DNMT3B7 transgenic mice exhibit altered embryonic development, including lymphopenia, craniofacial abnormalities, and cardiac defects, similar to Dnmt3b-deficient animals, but rarely develop cancer. However, when DNMT3B7 transgenic mice are bred with Emicro-Myc transgenic mice, which model aggressive B-cell lymphoma, DNMT3B7 expression increases the frequency of mediastinal lymphomas in Emicro-Myc animals. Emicro-Myc/DNMT3B7 mediastinal lymphomas have more chromosomal rearrangements, increased global DNA methylation levels, and more locus-specific perturbations in DNA methylation patterns compared with Emicro-Myc lymphomas. These data represent the first in vivo modeling of cancer-associated DNA methylation changes and suggest that truncated DNMT3B isoforms contribute to the redistribution of DNA methylation characterizing virtually every human tumor. PMID- 20587528 TI - Integrated profiling reveals a global correlation between epigenetic and genetic alterations in mesothelioma. AB - Development of mesothelioma is linked mainly to asbestos exposure, but the combined contributions of genetic and epigenetic alterations are unclear. We investigated the potential relationships between gene copy number (CN) alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n = 23). There were no instances of significantly correlated CN alteration and methylation at probed loci, whereas averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations. In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes. Further, there was evidence that this association was partially attributable to prevalent allele loss at the DNA methyltransferase gene DNMT1. Our findings define a strong association between global genetic and global epigenetic dysregulation in mesothelioma, rather than a discrete, local coordination of gene inactivation. PMID- 20587529 TI - Microtubule-disrupting chemotherapeutics result in enhanced proteasome-mediated degradation and disappearance of tubulin in neural cells. AB - We sought to examine the effects of microtubule-targeting agents (MTA) on neural cells to better understand the problem of neurotoxicity, their principal side effect, and to possibly develop a model of clinical toxicity. Studies showed that microtubule-depolymerizing agents (MDA) not only disassembled microtubules in neural HCN2 cells but also led to rapid disappearance of tubulin, and that this was specific for MDAs. Tubulin levels decreased to 20% as early as 8 hours after adding vincristine, and to 1% to 30% (mean, 9.8 +/- 7.6%; median of 7%) after 100 nmol/L vincristine for 24 hours. This disappearance was reversible. An increase in both glu-terminated and acetylated tubulin, markers of stable tubulin, preceded reaccumulation of soluble tubulin, suggesting a priority for stabilizing tubulin first as microtubules before replenishing the soluble pool. Similar results were shown with other MDAs. Furthermore, microtubule reassembly did not arise from a central focus but instead appeared to involve dispersed nucleation, as evidenced by the appearance of small, stable microtubule stubs throughout the cytoplasm. In contrast, experiments with four nonneural "normal" cell lines and four cancer cell lines resulted in microtubule destabilization but only modest tubulin degradation. Evidence for proteasome-mediated degradation was obtained by demonstrating that adding a proteasome inhibitor before vincristine prevented tubulin disappearance. In summary, MDAs lead to rapid disappearance of tubulin in neural but not in other normal or cancer cells. These results underscore the fine control that occurs in neural cells and may further our understanding of neurotoxicity following MDAs. PMID- 20587530 TI - Premetastatic lung "niche": is vascular endothelial growth factor receptor 1 activation required? AB - Inflammatory pathways may mediate preparation of the "metastatic soil" in the lungs. Some of these pathways--activation and/or the recruitment of certain inflammatory cells--might depend on vascular endothelial growth factor receptor 1 (VEGFR1) activity. Thus, blocking the activity of VEGFR1 (or the interaction with its ligands) has emerged as a potential antimetastasis strategy to target not only angiogenesis and cancer cell survival and migration, but also the recruitment of tumor growth-promoting bone marrow-derived cells (BMDC). However, inhibition of VEGFR1 activity by blocking antibodies or by genetic deletion of the tyrosine kinase domain neither prevented nor changed the rate of spontaneous metastasis formation after surgical removal of primary tumors. Thus, development of VEGFR1-targeted agents should be pursued in selected tumors (e.g., by identifying cancers that depend on VEGFR1 signaling for survival) or in specific combination therapies. Preventing metastasis will likely require identification and blockade of additional or alternative proinflammatory pathways that mediate the priming of the metastatic soil and the growth of micrometastases. PMID- 20587531 TI - A need for basic research on fluid-based early detection biomarkers. AB - Cancer continues to be a major cause of mortality despite decades of effort and expense. The problem reviewed here is that before many cancers are discovered they have already progressed to become drug resistant or metastatic. Biomarkers found in blood or other body fluids could supplement current clinical indicators to permit earlier detection and thereby reduce cancer mortality. PMID- 20587532 TI - Targeting epidermal growth factor receptor-associated signaling pathways in non small cell lung cancer cells: implication in radiation response. AB - Several studies have shown solid evidence for the potential value of targeting epidermal growth factor receptor (EGFR) signaling to enhance the antitumor activity of radiation. However, therapeutic resistance has emerged as an important clinical issue. Here, we investigated whether strategies for targeting EGFR-associated downstream signaling would radiosensitize a panel of non-small cell lung cancer cell lines. Inhibition of K-RAS using RNA interference attenuated downstream signaling and increased radiosensitivity of A549 and H460 cells, whereas inhibition of EGFR did not. A549 cells harboring a K-RAS mutation at codon V12 were radiosensitized by small interfering RNA (siRNA) targeting this codon. H460 cells having mutation at codon V61 was radiosensitized by siRNA targeting of this mutation. K-RAS siRNA did not radiosensitize H1299 cells possessing wild-type K-RAS. Inhibition of the phosphoinositide 3-kinase (PI3K) AKT-mammalian target of rapamycin pathway led to significant radiosensitization of the two cell lines, whereas selective inhibition of extracellular signal regulated kinase signaling did not. Inhibitors targeting the PI3K-AKT-mTOR pathway also abrogated G(2) arrest following irradiation and induced gammaH2AX foci formation. A dual inhibitor of class I PI3K and mammalian target of rapamycin effectively increased the radiosensitivity of A549 and H460 cells. Inhibition of PI3K-AKT signaling was associated with the downregulation of DNA PKs. Although apoptosis was the primary mode of cell death when cells were pretreated with LY294002 or AKT inhibitor VIII, cells pretreated with rapamycin or PI-103 showed mixed modes of cell death, including apoptosis and autophagy. Our results suggest possible mechanisms for counteracting EGFR prosurvival signaling implicated in radioresistance and offer an alternative strategy for overcoming resistance to EGFR inhibitors used in combination with irradiation. PMID- 20587533 TI - The pan-Bcl-2 inhibitor (-)-gossypol triggers autophagic cell death in malignant glioma. AB - Antiapoptotic Bcl-2 family members suppress both apoptosis and autophagy and are of major importance for therapy resistance of malignant gliomas. To target these molecules, we used BH3 mimetics and analyzed the molecular mechanisms of cell death induced thereby. Glioma cells displayed only limited sensitivity to single agent treatment with the BH3 mimetics HA14-1, BH3I-2', and ABT-737, whereas the pan-Bcl-2 inhibitor (-)-gossypol efficiently induced cell death. Furthermore, (-) gossypol potentiated cell death induced by temozolomide (TMZ) in MGMT (O(6) methylguanine-DNA methyltransferase)-negative U343 cells and, to a lesser extent, in MGMT-expressing U87 cells. (-)-Gossypol triggered translocation of light chain 3 to autophagosomes and lysosomes and cytochrome c release, but cell death occurred in the absence of lysosomal damage and effector caspase activation. Lentiviral knockdown of Beclin1 and Atg5 in U87, U343, and MZ-54 cells strongly diminished the extent of cell death induced by (-)-gossypol and combined treatment with TMZ, indicating that autophagy contributed to this type of cell death. In contrast, stable knockdown of the endogenous autophagy inhibitor mammalian target of rapamycin increased autophagic cell death. Our data suggest that pan-Bcl-2 inhibitors are promising drugs that induce caspase-independent, autophagic cell death in apoptosis-resistant malignant glioma cells and augment the action of TMZ. Furthermore, they indicate that efficient killing of glioma cells requires neutralization of Mcl-1. PMID- 20587534 TI - Functional characterization of a cancer causing mutation in human replication protein A. AB - Replication protein A (RPA) is the primary ssDNA-binding protein in eukaryotes. RPA is essential for DNA replication, repair, and recombination. Mutation of a conserved leucine residue to proline in the high-affinity DNA binding site of RPA (residue L221 in human RPA) has been shown to have defects in DNA repair and a high rate of chromosomal rearrangements in yeast. The homologous mutation in mice was found to be lethal when homozygous and to cause high rates of cancer when heterozygous. To understand the molecular defect causing these phenotypes, we created the homologous mutation in the human RPA1 gene (L221P) and analyzed its properties in cells and in vitro. RPA1(L221P) does not support cell cycle progression when it is the only form of RPA1 in HeLa cells. This phenotype is caused by defects in DNA replication and repair. No phenotype is observed when cells contain both wild-type and L221P forms of RPA1, indicating that L221P is not dominant. Recombinant L221P polypeptide forms a stable complex with the other subunits of RPA, indicating that the mutation does not destabilize the protein; however, the resulting complex has dramatically reduced ssDNA binding activity and cannot support SV40 DNA replication in vitro. These findings indicate that in mammals, the L221P mutation causes a defect in ssDNA binding and a nonfunctional protein complex. This suggests that haploinsufficiency of RPA causes an increase in the levels of DNA damage and in the incidence of cancer. PMID- 20587536 TI - Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow-up. AB - BACKGROUND: Concurrent alcohol exposure has been associated with reduced fecundity, but no studies have estimated the effect of prenatal alcohol exposure on male fecundity. The aim of this study was to investigate the association between maternal alcohol consumption during pregnancy, semen quality and levels of reproductive hormones in young, adult men. METHODS: From a Danish pregnancy cohort established in 1984-1987, 347 sons were selected for a follow-up study conducted in 2005-2006. Semen and blood samples were analyzed for conventional semen characteristics and reproductive hormones, respectively, and results were related to prospectively self-reported information on maternal alcohol consumption during pregnancy. RESULTS: The sperm concentration decreased with increasing prenatal alcohol exposure. The adjusted mean sperm concentration among sons of mothers drinking >or=4.5 drinks per week during pregnancy was 40 (95% CI: 25-60) millions/ml. This concentration was approximately 32% lower compared with men exposed to <1.0 drink per week, who had a sperm concentration of 59 (95% CI: 44-77) millions/ml. The semen volume and the total sperm count were also associated with prenatal alcohol exposure; sons prenatally exposed to 1.0-1.5 drinks per week had the highest values. No associations were found for sperm motility, sperm morphology or any of the reproductive hormones, including testosterone. CONCLUSIONS: These results indicate that prenatal exposure to alcohol may have a persisting adverse effect on Sertoli cells, and thereby sperm concentration. If these associations are causal they could explain some of the reported differences between populations and long-term changes in semen quality. PMID- 20587537 TI - Patient state index vs bispectral index as measures of the electroencephalographic effects of propofol. AB - BACKGROUND: The patient state index (PSI) and the bispectral index (BIS) quantify anaesthetic depth based on the EEG using different algorithms. We compared both indices with regard to the prediction of the depth of propofol anaesthesia. METHODS: In 17 patients, propofol was infused until burst suppression occurred and stopped thereafter until BIS recovered to values above 60. This was repeated; afterwards, patients were intubated, for subsequent surgery. Without surgical stimulus, PSI and BIS were measured simultaneously and compared with the estimated effect-site concentrations of propofol. These were derived from simultaneous pharmacokinetic and -dynamic modelling in an individual two-stage and a population-based NONMEM approach. RESULTS: A close sigmoid relationship was observed between the propofol effect-site concentration and both PSI [coefficient of determination rho(2)=0.91 (sd 0.05)] and BIS [rho(2)=0.92 (0.03)], which was significantly steeper for PSI [gamma=2.2 (0.6)] than for BIS [gamma=1.8 (0.4)], and reached significantly lower values for PSI [E(max)=0.3 (1.1)] than for BIS [E(max)=5.3 (6.7)] at maximal propofol concentrations. A significantly smaller k(e0) was obtained for PSI [0.09 (0.03) min(-1)] compared with BIS [0.10 (0.02) min(-1)]. PSI and BIS correlated significantly with each other (rho(2)=0.866) and predicted propofol effect-site concentration with a comparable probability [P(K)=0.87 (0.05) and 0.86 (0.05), respectively]. NONMEM revealed E(0)=89.3 and 92.3, E(max)=1.9 and 8.6, C(e50)=1.38 and 1.92 microg ml(-1), gamma=1.6 and 1.48, and k(e0)=0.103 and 0.131 min(-1) as typical values for PSI and BIS, respectively. CONCLUSIONS: The PSI and the BIS monitors performed equally well in predicting depth of propofol anaesthesia. However, PSI was lower than BIS by approximately 10-15 points at high propofol concentrations. PMID- 20587535 TI - Long-term stability of demethylation after transient exposure to 5-aza-2' deoxycytidine correlates with sustained RNA polymerase II occupancy. AB - DNA methyltransferase inhibitors are currently the standard of care for myelodysplastic syndrome and are in clinical trials for leukemias and solid tumors. However, the molecular basis underlying their activity remains poorly understood. Here, we studied the induction and long-term stability of gene reactivation at three methylated tumor suppressor loci in response to the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-azaCdR) in human breast cancer cells. At the TMS1/ASC locus, treatment with 5-azaCdR resulted in partial DNA demethylation, the reengagement of RNA polymerase II (Pol II), and a shift from a repressive chromatin profile marked with H3K9me2 and H4K20me3 to an active profile enriched in H3ac and H3K4me2. Using a single-molecule approach coupling chromatin immunoprecipitation with bisulfite sequencing, we show that H3ac, H3K4me2, and Pol II selectively associated with the demethylated alleles, whereas H3K9me2 preferentially marked alleles resistant to demethylation. H4K20me3 was unaffected by DNA demethylation and associated with both unmethylated and methylated alleles. After drug removal, TMS1 underwent partial remethylation, yet a subset of alleles remained stably demethylated for over 3 months. These alleles remained selectively associated with H3K4me2, H3ac, and Pol II and correlated with a sustained low level of gene expression. TMS1 alleles reacquired H3K9me2 over time, and those alleles that became remethylated retained H3ac. In contrast, CDH1 and ESR1 were remethylated and completely silenced within approximately 1 week of drug removal, and failed to maintain stably unmethylated alleles. Our data suggest that the ability to maintain Pol II occupancy is a critical factor in the long-term stability of drug-induced CpG island demethylation. PMID- 20587538 TI - Saving the patient the radiation: no need for ECG-gating during cardiac computed tomography. PMID- 20587539 TI - A completely subcutaneous implantable cardioverter defibrillator system functioning simultaneously with an endocardial implantable cardioverter defibrillator programmed as pacemaker. AB - Because of multiple ventricular lead fractures with inappropriate shocks, a 31 year-old male received a completely subcutaneous implantable cardioverter defibrillator (ICD) system with the already existing 'endocardial' ICD functioning as an atrial pacemaker. PMID- 20587540 TI - Predictors of stroke in patients of tuberculous meningitis and its effect on the outcome. AB - BACKGROUND: Stroke is a devastating complication of tuberculous meningitis and is an important determinant of its outcome. AIM: To prospectively evaluate the predictive factors for stroke in patients with tuberculous meningitis and to assess the impact of stroke on the overall prognosis and outcome. METHODS: We evaluated and followed 100 patients of tuberculous meningitis for 6 months. Magnetic resonance imaging was performed at inclusion and after 6 months. We evaluated the predictors of stroke and also assessed the effect of stroke on the outcome. Outcome was defined with the help of modified Rankin scale. RESULTS: Of the 100 patients, 6 lost to follow-up. Thirty patients had stroke, 27 of them had stroke at inclusion. Three patients developed stroke during follow-up. In most of the patients, stroke was a manifestation of advanced stages of tuberculous meningitis. Internal capsule/basal ganglia were the most frequently involved sites. Infarcts commonly involved the middle cerebral arterial territory. On univariate analysis, predictors of stroke were aged >25 years (P < 0.001), cranial nerve involvement (P < 0.001), sylvian fissure exudates (P = 0.026), posterior fossa exudates (P = 0.016), optic chiasmal exudates (P = 0.04) and vision impairment (P = 0.004). Stage III tuberculous meningitis (P < 0.001) was also a predictor of stroke. On multivariate analysis aged >25 years was found a significant predictor of stroke. Strokes in patients with tuberculous meningitis were associated with poor prognosis. CONCLUSION: Stroke occurred in 30% of cases with tuberculous meningitis. Advanced stage of tuberculous meningitis, basal exudates, optochiasmatic arachnoiditis and vision impairment were significant predictors of stroke. Stroke independently predicted the poor outcome of tuberculous meningitis. PMID- 20587541 TI - Phototherapy for allergic rhinitis: a prospective, randomized, single-blind, placebo-controlled study. AB - BACKGROUND: Phototherapy has a profound immunosuppressive effect, and phototherapeutic methods using both ultraviolet (UV) and visible light are therefore widely used for the therapy of various inflammatory skin diseases. It is also proposed that phototherapy, using a combination of UV-A (25%), UV-B (5%) and visible light (70%), may represent a therapeutic alternative in patients with allergic rhinitis. METHOD: Seventy-nine patients were randomly assigned to receive either a combination of UV-A (25%), UV-B (5%) and visible light (70%), in the phototherapy group, or low-intensity visible light, in the control group. The efficacy of treatment was assessed by means of total nasal symptom score before treatment and 1 month after the end of treatment. RESULTS: Total nasal scores decreased in both groups but the decrease was highly significant in the active treatment group when compared with the placebo (p < 0.001). CONCLUSIONS: This study demonstrates that phototherapy may be an effective modality in the treatment of allergic rhinitis especially in cases of which commonly used drugs either are contraindicated and/or have insufficient efficacy. PMID- 20587542 TI - PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1. AB - The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD 1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2, had a delayed interaction reminiscent of a phenomenon of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was not restricted to PD-1 binding since PD-L1 behaved in a similar manner with its second ligand, CD80. Finally, we could demonstrate that PD-L1 and PD-L2 competed for PD-1 binding and conversely, an antagonist PD-1 mAb blocked both PD-L1 and PD L2 binding to PD-1 and strongly enhanced T-cell proliferation. These data further emphasize the differential molecular mechanisms of interaction of PD-L1 and PD-L2 with PD-1, and suggest possible new approach for the therapy of chronic infection, cancer and transplantation. PMID- 20587543 TI - The ELF panel: a new crystal ball in hepatology? PMID- 20587545 TI - Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy. AB - BACKGROUND AND AIMS: Concomitant use of immunosuppressants (IS) with scheduled infliximab (IFX) maintenance therapy for Crohn's disease (CD) or ulcerative colitis (UC) is debated. The aim of this study was to assess whether IS co treatment is useful in patients with inflammatory bowel disease (IBD) on scheduled IFX infusions. METHODS: 121 consecutive patients with IBD (23 UC, 98 CD) treated by IFX and who received at least 6 months of IS co-treatment (azathioprine (AZA) or methotrexate (MTX)) were studied. In each patient, the IFX treatment duration was divided into semesters which were independently analysed regarding IBD activity. RESULTS: Semesters with IS (n=265) and without IS (n=319) were analysed. IBD flares, perianal complications and switch to adalimumab were less frequently observed in semesters with IS than in those without IS (respectively: 19.3% vs 32.0%, p=0.003; 4.1% vs 11.8%, p=0.03; 1.1% vs 5.3%, p=0.006). Maximal C-reactive protein (CRP) level and IFX dose/kg observed during the semesters were lower in semesters with IS. Within semesters with IS, IBD flares and perianal complications were less frequently observed in semesters with AZA than in those with MTX. In multivariate analysis, IS co-treatment was associated with a decreased risk of IBD flare (OR 0.52; 95% CI 0.35 to 0.79) CONCLUSION: In patients with IBD receiving IFX maintenance therapy, IS co treatment is associated with reduced IBD activity, IFX dose and switch to adalimumab. In this setting, co-treatment with AZA seems to be more effective than co-treatment with MTX. Benefit of such a combination treatment has to be balanced with potential risks, notably infections and cancers. PMID- 20587546 TI - Interferon gamma receptor 2 gene variants are associated with liver fibrosis in patients with chronic hepatitis C infection. AB - BACKGROUND: Only a minority of patients with chronic hepatitis C virus (HCV) infection develops severe liver fibrosis, a process that may be controlled by human genetic factors. OBJECTIVE: To investigate the role of 384 single nucleotide polymorphisms (SNPs) located in 36 candidate genes related to the fibrogenesis/fibrolysis process. METHODS: Patients with chronic HCV infection were gathered from two French cohorts (prospectively and retrospectively). The overall sample consisted of 393 HCV-infected subjects without known risk factors for fibrosis progression, including 134 patients with severe liver fibrosis and 259 without severe fibrosis. RESULTS: Only two SNPs in strong linkage disequilibrium (LD) in the interferon gamma receptor 2 gene (IFNGR2) were significantly associated with liver fibrosis in both the prospective and the retrospective samples. The strongest association (p=8x10(-5)) was observed with the G/A SNP rs9976971 with an OR of severe fibrosis for AA versus AG or GG subjects at 2.95 (95% CI 1.70 to 5.11). This effect was higher (p=9x10(-7)) when taking into account the time of follow-up, and the hazard ratio of progression towards severe fibrosis for AA patients was 2.62 (1.76 to 3.91). Refined sequencing and analysis of the IFNGR2 region identified two additional variants in strong LD with rs9976971. No haplotypes derived from this cluster of four variants provided stronger evidence for association than rs9976971 alone. CONCLUSIONS: This identification of a cluster of four IFNGR2 variants strongly associated with fibrosis progression in chronic HCV infection underlines the role of IFNgamma in the development of liver fibrosis that may pave the way for new treatments. PMID- 20587547 TI - In vivo action of trefoil factor 2 (TFF2) to speed gastric repair is independent of cyclooxygenase. AB - OBJECTIVE: Trefoil factor (TFF) peptides are expressed in gastric tissues, where they are part of the epithelial defences. To complement previous in vitro work, the goal of the present study was to examine directly if TFF2 was essential for gastric restitution in vivo during the recovery from microscopic damage. DESIGN: TFF2 mutant (KO) mice were examined to study the epithelial repair process in vivo after laser-induced photodamage (LPD). Using two-photon laser energy absorption (710 nm), LPD was imposed on an approximately 3-5 cell region of surface epithelium in anaesthetised mouse stomach. Responses to damage were evaluated during confocal time-lapse microscopy; including area of damage and the extracellular pH adjacent to the damaged surface (Cl-NERF pH sensor). RESULTS: In control (TFF2+/+ and TFF2+/-) mice, damaged cells were exfoliated and the damaged epithelium was repaired by indomethacin. The resting surface pH was similar between control and TFF2-KO animals, but the post-LPD alkalisation of surface pH observed in control mice (pH 0.3 + or - 0.05, n=21) was attenuated in the TFF2-KO stomach (pH -0.08 + or - 0.09, n=18). Recobinant rat TFF3 partially rescued the attenuated surface pH change in TFF2-KO stomach, in the presence or absence of indomethacin. CONCLUSIONS: In the gastric epithelium in vivo, TFFs promote epithelial restitution via a mechanism that does not require cyclooxygenase activation. A novel role for TFFs to affect gastric surface pH is observed. PMID- 20587548 TI - Toll-like receptor 4 polymorphisms in German and US patients are not associated with occurrence or severity of acute pancreatitis. PMID- 20587549 TI - Sacral nerve stimulation for intractable constipation: was it really an intractable constipation? PMID- 20587550 TI - Abnormally expressed ER stress response chaperone Gp96 in CD favours adherent invasive Escherichia coli invasion. AB - BACKGROUND AND AIMS: Crohn's disease (CD) ileal lesions are colonised by pathogenic adherent-invasive Escherichia coli (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised stress response proteins, due to ER stress, is observed in patients with CD. The expression of the ER-localised stress response protein Gp96 in patients with CD and its biological role with regards to the ability of AIEC to invade intestinal epithelial cells were analysed. METHODS AND RESULTS: Immunohistochemistry on tissue arrays showed that, together with CEACAM6 (carcinoembryonic antigen related cell adhesion molecule 6) or the ER stress protein Grp78, Gp96 is also strongly expressed at the apical plasma membrane of the ileal epithelial cells of 50% of patients with CD. Invasion experiments in the presence of antibodies raised against Gp96, or after transfection of Intestine-407 cells with gp96 small interfering RNA (siRNA), indicated that Gp96 is essential to promote AIEC LF82 invasion, allowing, via the recognition of the outer membrane protein OmpA, OMVs to fuse with intestinal epithelial cells. CONCLUSIONS: Gp96 is overexpressed on the apical surface of ileal epithelial cells in patients with CD and acts as a host cell receptor for OMVs, promoting AIEC invasion. From the results shown here, it is speculated that AIEC could take advantage of the abnormal expression of Gp96 in patients with CD to invade the ileal mucosa. PMID- 20587553 TI - Locum staff. Responsibilities of individual doctors. PMID- 20587554 TI - Accidental strangulation with a Venetian blind cord--a near miss. PMID- 20587556 TI - NICE recommends widening choice of biological drugs for patients with rheumatoid arthritis. PMID- 20587551 TI - Fluorine-18-fluorodeoxyglucose positron emission tomography in response assessment before high-dose chemotherapy for lymphoma: a systematic review and meta-analysis. AB - BACKGROUND: We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkin's lymphoma (HL) and aggressive non-Hodgkin's lymphoma. METHODS: We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta analysis to determine prognostic accuracy. RESULTS: Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. (18)F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56-0.81) and specificity of 0.81 (95% CI, 0.73-0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity. CONCLUSION: (18)F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results. PMID- 20587559 TI - More US doctors are refusing to accept government insured patients. PMID- 20587560 TI - Students, you are not alone. PMID- 20587562 TI - Laser eye injuries. Further warnings about laser pointers. PMID- 20587563 TI - Dutch on male circumcision. Non-therapeutic excision of the foreskin. PMID- 20587564 TI - Dutch on male circumcision. Putting children first. PMID- 20587565 TI - Lower urinary symptoms in men. Older men: cataracts v prostates. PMID- 20587566 TI - Consider fledgling researchers. PMID- 20587567 TI - Falling research in the NHS. Abolish new research governance infrastructure. PMID- 20587568 TI - Falling research in the NHS. Research passports haven't streamlined processes. PMID- 20587569 TI - WHO and pandemic flu. Another question for GSK. PMID- 20587570 TI - Falling research in the NHS. Tackle deprofessionalisation and fragmentation. PMID- 20587571 TI - WHO and pandemic flu. There was also no new subtype. PMID- 20587572 TI - WHO and pandemic flu. Time for change, WHO. PMID- 20587573 TI - WHO Director-General replies to the BMJ. PMID- 20587574 TI - WHO and pandemic flu. GlaxoSmithKline UK responds. PMID- 20587575 TI - WHO and pandemic flu. What happened in Mexico. PMID- 20587576 TI - German appeal court ruling gives support to right to die campaign. PMID- 20587578 TI - Antivaccine lobby resists introduction of Hib vaccine in India. PMID- 20587580 TI - Polymorphisms in the endocannabinoid receptor 1 in relation to fat mass distribution. AB - OBJECTIVE: Both animal and human studies have associated the endocannabinoid system with obesity and markers of metabolic dysfunction. Blockade of the cannabinoid receptor 1 (CB1) caused weight loss and reduction in waist size in both obese and type II diabetics. Recent studies on common variants of the CB1 receptor gene (CNR1) and the link to obesity have been conflicting. The aim of the present study was to evaluate whether selected common variants of the CNR1 are associated with measures of obesity and fat distribution. DESIGN AND METHODS: The single nucleotide polymorphisms (SNPs) rs806381, rs10485179 and rs1049353 were genotyped, and body fat and fat distribution were assessed by the use of dual-energy X-ray absorptiometry and magnetic resonance imaging in a population based study comprising of 783 Danish men, aged 20-29 years. RESULTS: The rs806381 polymorphism was significantly associated with visceral fat mass (FM) only, whereas the rs1049353 was significantly and directly associated with visceral and intermuscular FM. None of the SNPs analysed were associated with total body FM or subcutaneous FM. CONCLUSION: The results point towards a link between common variants of the CNR1 and fat distribution in young men. PMID- 20587581 TI - Sleeping during the day: effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone. AB - BACKGROUND: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. METHODS: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. RESULT: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)+22%, P<0.05), and reduced glucose levels (AUC-7%, P<0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's<0.05). CONCLUSION: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples. PMID- 20587582 TI - Abnormal cardiac contractility in long-term exogenous subclinical hyperthyroid patients as demonstrated by two-dimensional echocardiography speckle tracking imaging. AB - BACKGROUND: Subclinical hyperthyroidism is associated with cardiovascular morbidity. Recent advances in echocardiography imaging have allowed sophisticated evaluation of myocardial tissue properties. OBJECTIVE: To investigate the myocardial effects of long-term exogenous subclinical hyperthyroidism using two dimensional speckle tracking echocardiography imaging (2D-STE). DESIGN: Prospective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups. PATIENTS AND METHODS: Totally 25 patients with a history of differentiated thyroid carcinoma on long-term TSH-suppressive levothyroxine (l-T(4)) substitution were randomized to persistent TSH-suppressive l-T(4) substitution (low-TSH group) or restoration of euthyroidism. Additionally 40 euthyroid controls were studied. RESULTS (PROPOSAL): At baseline, the group of patients showed normal left ventricular (LV) systolic function but impaired diastolic function as assessed with conventional echocardiographic parameters. Importantly, 2D-STE analysis demonstrated the presence of subclinical LV systolic and diastolic dysfunction with impaired circumferential and longitudinal strain and strain rate at the isovolumic relaxation time. After restoration of euthyroidism, a significant improvement in LV systolic and diastolic function as assessed with 2D-STE strain was observed. CONCLUSION: Prolonged subclinical hyperthyroidism leads to systolic and diastolic dysfunction, which is reversible after restoration of euthyroidism. 2D-STE is a more sensitive technique to evaluate subtle changes in LV performance of these patients. PMID- 20587583 TI - Hygrochastic capsule dehiscence supports safe site strategies in New Zealand alpine Veronica (Plantaginaceae). AB - BACKGROUND AND AIMS: Hygrochasy is a capsule-opening mechanism predominantly associated with plants in arid habitats, where it facilitates spatially and temporally restricted dispersal. Recently, hygrochastic capsules were described in detail for the first time in alpine Veronica in New Zealand. The aim of the present study was to investigate whether hygrochastic capsules are an adaptation of alpine Veronica to achieve directed dispersal to safe sites. We expect that by limiting dispersal to rainfall events, distances travelled by seeds are short and confine them to small habitat patches where both seedlings and adults have a greater chance of survival. METHODS: Dispersal distances of five hygrochastic Veronica were measured under laboratory and field conditions and the seed shadow was analysed. Habitat patch size of hygrochastic Veronica and related non hygrochastic species were estimated and compared. KEY RESULTS: Dispersal distances achieved by dispersal with raindrops did not exceed 1 m but weather conditions could influence the even distribution of seeds around the parent plant. Compared with related Veronica species, hygrochastic Veronica mostly grow in small, restricted habitat patches surrounded by distinctly different habitats. These habitat patches provide safe sites for seeds due to their microtopography and occurrence of adult cushion plants. Non-hygrochastic Veronica can be predominantly found in large habitats without clearly defined borders and can be spread over long distances along rivers. CONCLUSIONS: The results suggest that hygrochasy is a very effective mechanism of restricting seed dispersal to rainfall events and ensuring short-distance dispersal within a small habitat patch. It appears that it is an adaptation for directed dispersal to safe sites that only exist within the parent habitat. PMID- 20587584 TI - Continuous glucose monitoring--coming of age. PMID- 20587585 TI - Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. AB - BACKGROUND: Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors. METHODS: In this 1-year, multicenter, randomized, controlled trial, we compared the efficacy of sensor-augmented pump therapy (pump therapy) with that of a regimen of multiple daily insulin injections (injection therapy) in 485 patients (329 adults and 156 children) with inadequately controlled type 1 diabetes. Patients received recombinant insulin analogues and were supervised by expert clinical teams. The primary end point was the change from the baseline glycated hemoglobin level. RESULTS: At 1 year, the baseline mean glycated hemoglobin level (8.3% in the two study groups) had decreased to 7.5% in the pump-therapy group, as compared with 8.1% in the injection-therapy group (P<0.001). The proportion of patients who reached the glycated hemoglobin target (<7%) was greater in the pump-therapy group than in the injection-therapy group. The rate of severe hypoglycemia in the pump-therapy group (13.31 cases per 100 person-years) did not differ significantly from that in the injection-therapy group (13.48 per 100 person years, P=0.58). There was no significant weight gain in either group. CONCLUSIONS: In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (Funded by Medtronic and others; ClinicalTrials.gov number, NCT00417989.) PMID- 20587586 TI - Reduction in risk of progression of diabetic retinopathy. PMID- 20587588 TI - Comprehensive analysis of the palindromic motif TCTCGCGAGA: a regulatory element of the HNRNPK promoter. AB - Definitive identification of promoters, their cis-regulatory motifs, and their trans-acting proteins requires experimental analysis. To define the HNRNPK promoter and its cognate DNA-protein interactions, we performed a comprehensive study combining experimental approaches, including luciferase reporter gene assays, chromatin immunoprecipitations (ChIP), electrophoretic mobility shift assays (EMSA), and mass spectrometry (MS). We discovered that out of the four potential HNRNPK promoters tested, the one containing the palindromic motif TCTCGCGAGA exhibited the highest activity in a reporter system assay. Although further EMSA and MS analyses, performed to uncover the identity of the palindrome binding transcription factor, did identify a complex of DNA-binding proteins, neither method unambiguously identified the pertinent direct trans-acting protein(s). ChIP revealed similar chromatin states at the promoters with the palindromic motif and at housekeeping gene promoters. A ChIP survey showed significantly higher recruitment of PARP1, a protein identified by MS as ubiquitously attached to DNA probes, within heterochromatin sites. Computational analyses indicated that this palindrome displays features that mark nucleosome boundaries, causing the surrounding DNA landscape to be constitutively open. Our strategy of diverse approaches facilitated the direct characterization of various molecular properties of HNRNPK promoter bearing the palindromic motif TCTCGCGAGA, despite the obstacles that accompany in vitro methods. PMID- 20587590 TI - NF1 inactivation revs up Ras in adult acute myelogenous leukemia. AB - Mutations in the Ras pathway are common in myeloid malignancies. NF1, a tumor suppressor and negative regulator of Ras, is inactivated in a subset of adult acute myelogenous leukemia (AML) cases. Loss of NF1 function sensitizes cells to inhibition of mammalian target of rapamycin (mTOR), a downstream effector of Ras activation, highlighting a potential therapeutic opportunity for some AML patients. PMID- 20587589 TI - A possible role for short introns in the acquisition of stroma-targeting peptides in the flagellate Euglena gracilis. AB - The chloroplasts of Euglena gracilis bounded by three membranes arose via secondary endosymbiosis of a green alga in a heterotrophic euglenozoan host. Many genes were transferred from symbiont to the host nucleus. A subset of Euglena nuclear genes of predominately symbiont, but also host, or other origin have obtained complex presequences required for chloroplast targeting. This study has revealed the presence of short introns (41-93 bp) either in the second half of presequence-encoding regions or shortly downstream of them in nine nucleus encoded E. gracilis genes for chloroplast proteins (Eno29, GapA, PetA, PetF, PetJ, PsaF, PsbM, PsbO, and PsbW). In addition, the E. gracilis Pbgd gene contains two introns in the second half of presequence-encoding region and one at the border of presequence-mature peptide-encoding region. Ten of 12 introns present within presequence-encoding regions or shortly downstream of them identified in this study have typical eukaryotic GT/AG borders, are T-rich, 45-50 bp long, and pairwise sequence identities range from 27 to 61%. Thus single recombination events might have been mediated via these cis-spliced introns. A double crossing over between these cis-spliced introns and trans-spliced introns present in 5'-UTRs of Euglena nuclear genes is also likely to have occurred. Thus introns and exon-shuffling could have had an important role in the acquisition of chloroplast targeting signals in E. gracilis. The results are consistent with a late origin of photosynthetic euglenids. PMID- 20587591 TI - Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma. AB - PURPOSE: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts. EXPERIMENTAL DESIGN: The IL-27 direct antitumor activity on MM cells was investigated in terms of angiogenesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differentiation and function was also tested. In vivo studies were done using severe combined immunodeficient/nonobese diabetic mice injected with MM cell lines. Tumors from IL-27- and PBS-treated mice were analyzed by immunohistochemistry and PCR array. RESULTS: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell lines through inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced osteoblast proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibition of angiogenesis. CONCLUSIONS: These findings show that IL-27 may represent a novel therapeutic agent capable of inhibiting directly MM cell growth as well as osteoclast differentiation and activity. PMID- 20587592 TI - Syncoilin modulates peripherin filament networks and is necessary for large calibre motor neurons. AB - Syncoilin is an atypical type III intermediate filament (IF) protein, which is expressed in muscle and is associated with the dystrophin-associated protein complex. Here, we show that syncoilin is expressed in both the central and peripheral nervous systems. Isoform Sync1 is dominant in the brain, but isoform Sync2 is dominant in the spinal cord and sciatic nerve. Peripherin is a type III IF protein that has been shown to colocalise and interact with syncoilin. Our analyses suggest that syncoilin might function to modulate formation of peripherin filament networks through binding to peripherin isoforms. Peripherin is associated with the disease amyotrophic lateral sclerosis (ALS), thus establishing a link between syncoilin and ALS. A neuronal analysis of the syncoilin-null mouse (Sync(-/-)) revealed a reduced ability in accelerating treadmill and rotarod tests. This phenotype might be attributable to the impaired function of extensor digitorum longus muscle and type IIb fibres caused by a shift from large- to small-calibre motor axons in the ventral root. PMID- 20587594 TI - Btk-dependent Rac activation and actin rearrangement following FcepsilonRI aggregation promotes enhanced chemotactic responses of mast cells. AB - Mast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E(2), is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (FcepsilonRI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)Cgamma-mediated Ca(2+) mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF, adenosine and PGE(2) were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk(-/-) mice. There were corresponding decreases in the PLCgamma-mediated Ca(2+) signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses. PMID- 20587593 TI - Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS induced inflammation to mitochondrial biogenesis. AB - The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFkappaB, and identified interspecies conserved kappaB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFkappaB, and in LPS-treated hepatocytes, NFkappaB served as an NRF1 enhancer element in conjunction with NFkappaB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis acting kappaB-element mutations, and nuclear accumulation of NFkappaB and CREB demonstrated dependence on mitochondrial H(2)O(2). These findings indicate that TLR4-dependent NFkappaB and CREB activation co-regulate the NRF1 promoter with NFkappaB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses. PMID- 20587595 TI - Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1 Orai1-dependent store-operated Ca2+ entry. AB - Store-operated Ca(2+) entry (SOCE) is established by formation of subplasmalemmal clusters of the endoplasmic reticulum (ER) protein, stromal interacting molecule 1 (STIM1) upon ER Ca(2+) depletion. Thereby, STIM1 couples to plasma membrane channels such as Orai1. Thus, a close proximity of ER domains to the plasma membrane is a prerequisite for SOCE activation, challenging the concept of local Ca(2+) buffering by mitochondria as being essential for SOCE. This study assesses the impact of mitochondrial Ca(2+) handling and motility on STIM1-Orai1-dependent SOCE. High-resolution microscopy showed only 10% of subplasmalemmal STIM1 clusters to be colocalized with mitochondria. Impairments of mitochondrial Ca(2+) handling by inhibition of mitochondrial Na(+)-Ca(2+) exchanger (NCX(mito)) or depolarization only partially suppressed Ca(2+) entry in cells overexpressing STIM1-Orai1. However, SOCE was completely abolished when both NCX(mito) was inhibited and the inner mitochondrial membrane was depolarized, in STIM1- and Orai1-overexpressing cells. Immobilization of mitochondria by expression of mAKAP RFP-CAAX, a construct that physically links mitochondria to the plasma membrane, affected the Ca(2+) handling of the organelles but not the activity of SOCE. Our observations indicate that mitochondrial Ca(2+) uptake, including reversal of NCX(mito), is fundamental for STIM1-Orai1-dependent SOCE, whereas the proximity of mitochondria to STIM1-Orai1 SOCE units and their motility is not required. PMID- 20587596 TI - Older and wiser? An affective science perspective on age-related challenges in financial decision making. AB - Financial planning decisionss are fundamentally affective in nature; they are decisions related to money, longevity and quality of life. Over the next several decades people will be increasingly responsible for managing their own assets and investments, and they will be subject to the affective influences on active, personal decision-making. Many of these crucial decisions are made and revised across the lifespan, including when to buy or sell a home, how to save for childrens' education, how to manage healthcare costs, when to retire, how much to save for retirement and how to allocate retirement funds. As average life expectancy increases, many retirees will be faced with inadequate savings to live comfortably until the end of their lives. In the current article, we examine the problems of and potential solutions to inadequate financial planning through the lens of affective science, with an emphasis on how brain-based changes in affective processing with age might contribute to the challenge of financial planning. PMID- 20587597 TI - An rTMS study into self-face recognition using video-morphing technique. AB - Self-face recognition is a sign of higher order self-awareness. Research into the neuronal network argues that the visual pathway of recognizing one's own face differs from recognizing others. The present study aimed at investigating the cortical network of self-other discrimination by producing virtual lesions over the temporo-parietal junction and the prefrontal cortex using low-frequency repetitive transcranial magnetic stimulation (rTMS) in a sham-controlled design. Frontal and parietal areas were stimulated separately in consecutive sessions one week apart in 10 healthy subjects. We designed a video-task comprising morphings of famous, unfamiliar and the subjects' own faces that transformed into each other over a time period of six seconds. Reaction time (RT) was measured by pushing a mouse-button once a change of identity was recognized. rTMS over the right temporo-parietal junction led to a decrease in RT when a subject's own face emerged from a familiar face; a similar effect was observed after rTMS over right prefrontal and left-parietal cortices, when the subjects' ratings of own likeability were taken into account. The transition from an unfamiliar face to one's own face indicated a left frontal lateralization. PMID- 20587598 TI - Mutual gaze in Alzheimer's disease, frontotemporal and semantic dementia couples. AB - Alzheimer's disease (AD), frontotemporal dementia (FTD) and semantic dementia (SD) are neurodegenerative diseases that differ in their socioemotional presentations. Mutual gaze (i.e. when two individuals make eye contact) is a building block of social behavior that may be differentially affected by these diseases. We studied 13 AD patients, 11 FTD patients, 9 SD patients and 22 normal controls as they engaged in conversations with partners about relationship conflicts. Physiological reactivity was monitored during the conversations and trained raters coded mutual gaze from videotaped recordings. Results indicated that mutual gaze was preserved in AD couples. Mutual gaze was diminished in FTD couples while SD couples showed evidence of greater mutual gaze. SD couples also showed lower physiological reactivity compared to controls. Across patient groups, reduced mutual gaze was associated with greater behavioral disturbance as measured by the Neuropsychiatric Inventory, especially on the disinhibition and apathy subscales. These results point to subtle differences between the three types of dementia in the social realm that help to illuminate the nature of the disease process and could aid in differential diagnosis. PMID- 20587599 TI - The Munich Myocardial Infarction Registry: impact of C-reactive protein and kidney function on hospital mortality in diabetic patients. AB - INTRODUCTION: The aim of this study was to analyse hospital mortality with regards to the presence of diabetes, elevation of C-reactive protein (CRP) levels and impaired kidney function (IKF) on admission. METHODS: All patients in the Munich Myocardial Infarction Registry (1999-2004, n = 2,015) were assessed. In both the diabetic (n = 770, 38%) and non-diabetic (n = 1,245, 61.2%) groups, CRP and kidney function on admission were analysed with regards to hospital outcome. RESULTS: In diabetic patients, both a CRP level >7 mg/L and a glomerular filtration rate (GFR) < 60 ml/min were independent risk factors for mortality (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-6.9 and OR 4.4, 95% CI 2.4 8.3, respectively). In non-diabetic patients with CRP levels equal or below the median and absence of IKF, hospital mortality was 0.7% whereas the presence of the triad of diabetes, CRP levels above the median and IKF increased hospital mortality to 23.5%. CONCLUSION: The registry demonstrates that the presence of the triad of diabetes, elevated CRP levels and reduced GFR on admission is associated with an excessive hospital mortality. Optimised early interventions are to be initiated to potentially overcome the unfavourable prognosis. PMID- 20587600 TI - Cardiovascular disease among diabetic in-patients at a tertiary hospital in Jamaica. PMID- 20587601 TI - Disempowered doctors? A relational view of public health policy implementation in urban India. AB - This article analyses the nature of power relationships between urban hospital practitioners and other groups of actors involved in the implementation of public health policies in India, and the effects of enacting different strategies to strengthen implementation, in the context of these balances of power. It is based on an empirical research study conducted over 18 months in five Indian cities involving 61 in-depth interviews with medical practitioners and policy actors, and an interpretivist analytical approach. An issue case study-of the implementation of national HIV testing guidelines-was used to focus the interviews on specific events and phenomena. Respondents' accounts revealed that practitioners in both private and government hospitals tended to successfully resist or subvert the attempts of regulators and administrators to enforce the guidelines. However, in spite of often possessing perspectives and convictions that differed from the nationally sanctioned guidelines, practitioners were not able to effectively communicate these ideas to other health systems actors, or introduce them into mainstream policy discourse. The metaphor of public health guideline implementation throws light on the problematical nature of the power possessed by medical practitioners in relation to public health systems in India. Even as practitioners wield 'negative' power in their ability to resist authority, they appear to lack the 'positive' power to contribute intellectually to the policy process. This mix of political obduracy and intellectual demoralization among practitioners also underpins a subtle trend in public health, of the separation of the world of ideas from the world of actions. Study findings highlight that stronger regulations and provisions for accountability in Indian health systems critically need to be balanced by measures to develop collective intellectual capital and include the voices of frontline practitioners in public health policy discourse. PMID- 20587602 TI - Care arrangements of AIDS orphans and their relationship with children's psychosocial well-being in rural China. AB - There is an estimated 100,000 children orphaned by AIDS in China, but data on the care arrangement of these orphans are limited. In this study, we examine the relationship between AIDS orphans' care arrangement and their psychosocial well being among a sample of AIDS orphans in rural China. A total of 296 children who lost both parents to AIDS participated in the study, including 176 in orphanages, 90 in kinship care and 30 in community-based group homes. All participants completed a cross-sectional survey assessing their traumatic symptoms, physical health and schooling. Data reveal that the AIDS orphans in group homes reported the best outcomes in three domains of psychosocial well-being, followed by those in the orphanages and then the kinship care. The differences in psychosocial well being among the three groups of children persist after controlling for key demographic characteristics. The findings suggest that the appropriate care arrangement for AIDS orphans should be evaluated within the specific social and cultural context where the orphans live. In resource-poor regions or areas stricken hardest by the AIDS epidemic, kinship care may not sufficiently serve the needs of AIDS orphans. Community-based care models, with appropriate government and community support preserving the family style and low child-to caregiver ratio may constitute an effective and sustainable care model for the best interest of the AIDS orphans in developing countries. PMID- 20587603 TI - Penetrance for copy number variants associated with schizophrenia. AB - The discovery of 'high-risk' de novo copy number variants (CNVs) associated with neuropsychiatric disorders such as schizophrenia offers the opportunity to translate these findings into useful tools for clinical geneticists. However, this will require estimation of penetrance for these variants, which has not yet been properly considered. To facilitate this process, we estimated the penetrance of CNVs associated with schizophrenia, at 15q13.3, 1q21.1, 15q11.2, 17p12, 2p16.3, 16p13.1 and 16p11.2 with a novel Bayesian method applied to pooled data from published case-control studies. For these CNVs, penetrance for schizophrenia was between 2 and 7.4%, which contrasts with the much higher penetrance for schizophrenia of the 22q11.2 deletions found in velo-cardio-facial syndrome. The highest penetrance was for 15q13.3 deletion (6-9% in individual studies) and the lowest was for 15q11.2 (2%). CNVs confer much higher risk for schizophrenia than common variants, but their penetrance is substantially lower than Mendelian disorders or other syndromic conditions. Since these CNVs predispose to multiple disorders, including epilepsy, autism and intellectual impairment, penetrance estimates will also need to take into account diagnostic specificity, and their overall penetrance for any neuropsychiatric disorder is likely to be much higher. Thus, although CNVs are still far from being clinically useful or relevant to genetic counselling for specific disorders, their detection may hold an important clinical value in predicting negative developmental outcomes. PMID- 20587604 TI - Fine mapping of chromosome 15q25.1 lung cancer susceptibility in African Americans. AB - Several genome-wide association studies identified the chr15q25.1 region, which includes three nicotinic cholinergic receptor genes (CHRNA5-B4) and the cell proliferation gene (PSMA4), for its association with lung cancer risk in Caucasians. A haplotype and its tagging single nucleotide polymorphisms (SNPs) encompassing six genes from IREB2 to CHRNB4 were most strongly associated with lung cancer risk (OR = 1.3; P < 10(-20)). In order to narrow the region of association and identify potential causal variations, we performed a fine-mapping study using 77 SNPs in a 194 kb segment of the 15q25.1 region in a sample of 448 African-American lung cancer cases and 611 controls. Four regions, two SNPs and two distinct haplotypes from sliding window analyses, were associated with lung cancer. CHRNA5 rs17486278 G had OR = 1.28, 95% CI 1.07-1.54 and P = 0.008, whereas CHRNB4 rs7178270 G had OR = 0.78, 95% CI 0.66-0.94 and P = 0.008 for lung cancer risk. Lung cancer associations remained significant after pack-year adjustment. Rs7178270 decreased lung cancer risk in women but not in men; gender interaction P = 0.009. For two SNPs (rs7168796 A/G and rs7164594 A/G) upstream of PSMA4, lung cancer risks for people with haplotypes GG and AA were reduced compared with those with AG (OR = 0.56, 95% CI 0.38-0.82; P = 0.003 and OR = 0.73, 95% CI 0.59-0.90, P = 0.004, respectively). A four-SNP haplotype spanning CHRNA5 (rs11637635 C, rs17408276 T, rs16969968 G) and CHRNA3 (rs578776 G) was associated with increased lung cancer risk (P = 0.002). The identified regions contain SNPs predicted to affect gene regulation. There are multiple lung cancer risk loci in the 15q25.1 region in African-Americans. PMID- 20587609 TI - The role of the amino-terminal domain in the interaction of unliganded peroxisome proliferator-activated receptor gamma-2 with nuclear receptor co-repressor. AB - Peroxisome proliferator-activated receptor gamma-2 (PPARG2) is a ligand-dependent transcriptional factor involved in the pathogenesis of insulin resistance. In the presence of a ligand, PPARG2 associates with co-activators, while it recruits co repressors (CoRs) in the absence of a ligand. It has been reported that the interaction of liganded PPARG2 with co-activators is regulated by the amino terminal A/B domain (NTD) via inter-domain communication. However, the role of the NTD is unknown in the case of the interaction between unliganded PPARG2 and CoRs. To elucidate this, total elimination of the influence of ligands is required, but the endogenous ligands of PPARG2 have not been fully defined. PPARG1-P467L, a naturally occurring mutant of PPARG1, was identified in a patient with severe insulin resistance. Reflecting its very low affinity for various ligands, this mutant does not have transcriptional activity in the PPAR response element, but exhibits dominant negative effects (DNEs) on liganded wild-type PPARG2-mediated transactivation. Using the corresponding PPARG2 mutant, PPARG2 P495L, we evaluated the role of the NTD in the interaction between unliganded PPARG2 and CoRs. Interestingly, the DNE of PPARG2-P495L was increased by the truncation of its NTD. NTD deletion also enhanced the DNE of a chimeric receptor, PT, in which the ligand-binding domain of PPARG2 was replaced with that of thyroid hormone receptor beta-1. Moreover, NTD deletion facilitated the in vitro binding of nuclear receptor CoR with wild-type PPARG2, mutant P495L, and the PT chimera (PPARG2-THRB). Inter-domain communication in PPARG2 regulates not only ligand-dependent transactivation but also ligand-independent silencing. PMID- 20587610 TI - Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection. AB - Success rate in human pregnancies is believed to be very low and sex-specific mechanisms may operate in prenatal loss. Assuming a sex-differential in prenatal loss exists, we examined genetic markers in biologically plausible targets in the HLA complex, other immune system-related and iron-regulatory genes in 388 healthy newborns from Wales (UK) using one sex as a control group for the other. Genotyping of 333 single nucleotide polymorphisms (SNPs) from 107 genes was achieved mainly by TaqMan assays. Twenty-two of autosomal SNPs showed frequency differences between 187 male and 201 female newborns either individually or as part of a haplotype. Of these, six markers (RXRB rs2076310, HLA complex haplotype HLA-DQA1 rs1142316-HLA-DRA rs7192-HSPA1B rs1061581, HIST1H1T rs198844, IFNG rs2069727, NKG2D rs10772266 and IRF4 heterozygosity) showed statistically robust differences between male and female newborns and multivariable modeling confirmed their independence. There were fewer males homozygote for combined wildtype genotypes of LIF rs929271, TP53 rs1042522 and MDM2 rs2279744 compared with females [OR = 0.3, 95% confidence interval (CI) = 0.1-0.8; P < 0.01] although these SNPs did not show any association individually. It is unlikely that SNPs have clinical utility as single markers in any trait with complex etiology but polygenic predictive models remain a possibility. If their validity is confirmed in larger studies of different populations and functional mechanisms of these preliminary associations are elucidated, these markers from the HLA complex, NKG2D region and cytokines may cumulatively have sufficient predictive value for susceptibility to prenatal selection in each sex. PMID- 20587611 TI - Comparison of the sales of veterinary antibacterial agents between 10 European countries. AB - OBJECTIVES: To compare the sales of veterinary antibacterial agents between 10 European countries. METHODS: Data were compiled from published reports from the 10 countries. We express the usage as amounts sold of veterinary antibacterial agents per country and year, in mg active substances per kg biomass of slaughtered pigs, poultry and cattle plus estimated biomass of (live) dairy cattle for the corresponding year. RESULTS: The usage, as expressed in mg antibacterial drugs sold/kg biomass of slaughtered pigs, poultry and cattle and of (live) dairy cattle, varied from 18 to 188 mg/kg. The relative proportion of the various classes of antibacterial agents sold varied considerably. CONCLUSIONS: The apparent wide variations in the usage of veterinary antimicrobial agents between countries cannot be explained by differences in the animal species demographics alone. Further in-depth analyses are required to identify the factors underlying the observed differences. PMID- 20587612 TI - Fosfomycin versus other antibiotics for the treatment of cystitis: a meta analysis of randomized controlled trials. AB - BACKGROUND: Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics. OBJECTIVES: To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis. METHODS: We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics. RESULTS: Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98-1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12 0.97). CONCLUSIONS: In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients. PMID- 20587613 TI - Docetaxel-prednisolone combination therapy for Japanese patients with hormone refractory prostate cancer: a single institution experience. AB - OBJECTIVE: To evaluate the efficacy and toxicity of docetaxel plus prednisolone treatment in Japanese patients with hormone-refractory prostate cancer (HRPC). METHODS: From April 2004 through August 2008, we used docetaxel plus prednisolone to treat 55 HRPC patients (median age, 72 years). Eighteen patients (32.7%) had measurable soft tissue lesions, whereas 52 patients (94.5%) had bone metastases. During the 21-day treatment cycle, docetaxel (70 mg/m(2)) was administered once every 21 days and oral prednisolone (5 mg), twice daily. Prostate-specific antigen (PSA) response, defined as a reduction of at least 50% in the baseline levels for 4 weeks, was evaluated. RESULTS: The median follow-up period was 30.1 months; median overall survival, 15.3 months and median progression-free survival, 7.5 months. During follow-up, 37 patients (67.3%) achieved the PSA response, and 5 of 18 (27.8%) patients with measurable disease showed a partial response. Among the 27 patients who experienced cancer pain before treatment initiation, 15 (55.5%) reduced their analgesic drug intake. Multivariate analysis of the prognostic variables revealed a significant association between the overall survival and pain (P = 0.033). Hematological toxicity (grades 3-4) included neutropenia (87.3%), febrile neutropenia (25.5%) and thrombocytopenia (5.5%). Frequent non-hematological adverse events were general edema (52.7%), general fatigue (32.7%) and sensory neuropathy (30.9%). Three patients died of adult respiratory distress syndrome (ARDS). CONCLUSION: Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did. PMID- 20587614 TI - Prognosis of secondary acute myeloid leukemia is affected by the type of the preceding hematologic disorders and the presence of trisomy 8. AB - BACKGROUND: Differences in the clinical course of secondary acute myeloid leukemia according to the type of the preceding disorders are not defined. We compared the outcomes of therapy-related acute myeloid leukemia, acute myeloid leukemia following myelodysplastic syndrome and acute myeloiod leukemia following myeloproliferative neoplasm. We also intended to find prognostic factors in secondary acute myeloid leukemia overall. METHODS: Retrospective medical record review at Seoul National University Hospital was performed. We assessed response to induction chemotherapy and overall survival. RESULTS: Ninety-five secondary acute myeloid leukemia patients (median age of 56.4 years) were analyzed. Twenty six, 57 and 12 patients had therapy-related leukemia, leukemia following myelodysplastic syndrome and myeloproliferative neoplasm, respectively. For patients receiving induction chemotherapy, complete remission rate was 47.5% and complete remission rate was different according to the type of the preceding disorders (P = 0.004). Compared to therapy-related leukemia (P = 0.027) and leukemia following myelodysplastic syndrome (P = 0.050), leukemia following myeloproliferative neoplasm had shorter overall survival. In secondary leukemia, presence of trisomy 8 had a prognostic impact (P = 0.003) along with cytogenetic risk group (P = 0.016). In multivariate analysis, the type of the preceding disorders (P = 0.026), 5q deletion (P = 0.015) and trisomy 8 (P = 0.040) were independent prognostic factors. CONCLUSIONS: Prognosis of secondary acute myeloid leukemia was different according to the type of the preceding disorders with the worst prognosis in leukemia following myeloprolfierative neoplasm. Along with cytogenetic risk grouping, trisomy 8 had a poor prognostic impact in secondary acute myeloid leukemia. PMID- 20587616 TI - Clinical and economic evaluation of first-line therapy with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer. AB - OBJECTIVE: Recently, significant progress in treatment of metastatic colorectal cancer has been achieved. Either FOLFIRI (fluorouracil, leucovorin and irinotecan) or modified FOLFOX6 (fluorouracil, leucovorin and oxaliplatin, oxaliplatin dose 85 mg/m(2)) is selected as first-line therapy in clinical practice in Japan. However, economic burden of colorectal cancer is considerable. METHODS: Analysis was made for all patients who were treated with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer. Regimen of FOLFIRI was compared with modified FOLFOX6 under consideration from clinical and economic standpoints. Progression free survival, response, toxicity and cancer care cost in patients with metastatic colorectal cancer was analyzed. Direct costs based on the fee schedule of the Japanese national health insurance were calculated. RESULTS: Median progression free survival was 7.7 months for FOLFIRI versus 8.4 months for modified FOLFOX6 (P = 0.48). Overall cost for first four cycles was yen756 284 for FOLFIRI and yen1 081 162 for modified FOLFOX6 (P < 0.0001). All grade alopecia was significantly more frequent with FOLFIRI than with modified FOLFOX6 (P = 0.04). All grade neuropathy was more observed with modified FOLFOX6 than FOLFIRI (P = 0.0002). CONCLUSIONS: FOLFIRI is inexpensive in the initial stage of treatment which a number of patients can receive chemotherapy than modified FOLFOX6 as first-line therapy for metastatic colorectal cancer in Japanese national insurance system. PMID- 20587617 TI - A case of pulmonary epithelioid hemangioendothelioma. PMID- 20587618 TI - Comparison of time trends in melanoma of skin cancer mortality (1990-2006) between countries based on the WHO mortality database. PMID- 20587619 TI - Genome-wide computational identification and manual annotation of human long noncoding RNA genes. AB - Experimental evidence suggests that half or more of the mammalian transcriptome consists of noncoding RNA. Noncoding RNAs are divided into short noncoding RNAs (including microRNAs) and long noncoding RNAs (lncRNAs). We defined complementary DNAs (cDNAs) lacking any positive-strand open reading frames (ORFs) longer than 30 amino acids, as well as cDNAs lacking any evidence of interspecies conservation of their longer-than-30-amino acid ORFs, as noncoding. We have identified 5446 lncRNA genes in the human genome from approximately 24,000 full length cDNAs, using our new ORF-prediction pipeline. We combined them nonredundantly with lncRNAs from four published sources to derive 6736 lncRNA genes. In an effort to distinguish standalone and antisense lncRNA genes from database artifacts, we stratified our catalog of lncRNAs according to the distance between each lncRNA gene candidate and its nearest known protein-coding gene. We concurrently examined the protein-coding capacity of known genes overlapping with lncRNAs. Remarkably, 62% of known genes with "hypothetical protein" names actually lacked protein-coding capacity. This study has greatly expanded the known human lncRNA catalog, increased its accuracy through manual annotation of cDNA-to-genome alignments, and revealed that a large set of hypothetical-protein genes in GenBank lacks protein-coding capacity. In addition, we have developed, independently of existing NCBI tools, command-line programs with high-throughput ORF-finding and BLASTP-parsing functionality, suitable for future automated assessments of protein-coding capacity of novel transcripts. PMID- 20587620 TI - Transcriptome profiling and network analysis of genetically hypertensive mice identifies potential pharmacological targets of hypertension. AB - Hypertension is a condition with major cardiovascular and renal complications, affecting nearly a billion patients worldwide. Few validated gene targets are available for pharmacological intervention, so there is a need to identify new biological pathways regulating blood pressure and containing novel targets for treatment. The genetically hypertensive "blood pressure high" (BPH), normotensive "blood pressure normal" (BPN), and hypotensive "blood pressure low" (BPL) inbred mouse strains are an ideal system to study differences in gene expression patterns that may represent such biological pathways. We profiled gene expression in liver, heart, kidney, and aorta from BPH, BPN, and BPL mice and determined which biological processes are enriched in observed organ-specific signatures. As a result, we identified multiple biological pathways linked to blood pressure phenotype that could serve as a source of candidate genes causal for hypertension. To distinguish in the kidney signature genes whose differential expression pattern may cause changes in blood pressure from those genes whose differential expression pattern results from changes in blood pressure, we integrated phenotype-associated genes into Genetic Bayesian networks. The integration of data from gene expression profiling and genetics networks is a valuable approach to identify novel potential targets for the pharmacological treatment of hypertension. PMID- 20587621 TI - Molecular cloning, expression, and initial characterization of members of the CYP3A family in horses. AB - The use of performance-enhancing drugs in the horse racing industry combined with the need for more rational approaches in the use of therapeutic agents in equids necessitates additional studies on the spectrum, content, and catalytic activities of hepatic cytochrome P450 monooxygenases in this species. In this study, three cytochrome P450 (P450) monooxygenases in the 3A family were cloned from, sequenced, and expressed in a baculovirus expression system. The proteins were designated CYP3A89, CYP3A96, and CYP3A97. Expression studies produced various results among the three proteins. CYP3A89 appears to undergo post translational modification, producing a truncated protein, and although metabolically active, CYP3A97 did not have a detectable P450 spectrum. Expression of CYP3A96 produced a full-length, catalytically active protein. CYP3A96 catalyzed testosterone, and nifedipine metabolism was 20- and 10-fold slower, respectively, compared with the human counterpart, CYP3A4. Relative hepatic expression levels of each member of the CYP3A family, determined using quantitative reverse transcription-polymerase chain reaction, varied more than 1000-fold in individual horses. The results demonstrate substantial interspecies variability in metabolism of substrates by members of the CYP3A family in the horse and human and support the need to fully characterize 450-mediated metabolism in equids. These studies provide a framework for screening therapeutically useful drugs and provide a method for determination of metabolites of illegal performance-enhancing drugs without the time and expense of either in vivo studies or obtaining liver samples for in vitro analysis. PMID- 20587622 TI - Influence of cytidine deaminase on antitumor activity of 2'-deoxycytidine analogs in vitro and in vivo. AB - Antitumor 2'-deoxycytidine (dCyd) analogs such as gemcitabine (dFdC), cytarabine (Ara-C), and 2'-C-cyano-2'-deoxy-1-beta-d-arabinofuranosylcytosine (CNDAC) are activated by dCyd kinase, whereas cytidine deaminase (CDA) inactivates them by conversion to their uracil forms. To elucidate the relationship between the chemosensitivity to antitumor dCyd nucleosides and CDA expression, we established a stable line of human gastric carcinoma TMK-1 cells constitutively overexpressing CDA (TMK-1/CDA) and examined its chemosensitivity to antitumor dCyd analogs in vitro and in vivo. We observed comparable reactivity for dFdC and Ara-C, and the substrate reactivity of CNDAC to recombinant human CDA was more than 10 times less efficient than those of Ara-C and dFdC. Next, we examined the in vitro chemosensitivity of TMK-1/CDA and observed a marked decrease in the sensitivity of TMK-1/CDA to Ara-C, dFdC, and CNDAC compared with mock-transfected cells. In addition, we transplanted TMK-1/CDA cells into a nude mouse xenograft model and examined their in vivo chemosensitivity to CNDAC. The in vivo antitumor effect of CNDAC on TMK-1/CDA cells was substantially reduced compared with that of mice transplanted with mock-transfected cells. These results indicate that CDA could play an important role in regulating susceptibility to antitumor dCyd analogs in vitro and in vivo. In addition, the expression level of CDA was found to affect the antitumor activity of CNDAC, even though the substrate reactivity of CNDAC to CDA is relatively low. PMID- 20587623 TI - Nutritional status affects fluvastatin-induced hepatotoxicity and myopathy in rats. AB - Rats that consumed a high-fat and high-sucrose diet (HF diet) developed hepatic steatosis. Treatment of HF diet-fed rats with fluvastatin (8 mg/kg) was lethal, followed by an elevation in levels of plasma aspartate aminotransferase and creatine kinase activities and skeletal muscle toxicity. This study was conducted to determine whether nutritional status affects statin-induced adverse effects in rats. Fluvastatin treatment of rats fed the HF diet led to an increase in systemic exposure, suggesting altered metabolism and elimination. In fact, although hepatic multidrug resistance-associated protein (Mrp) 2 and multidrug resistance (Mdr) 1b protein levels were not significantly changed by fluvastatin treatment for 8 days of rats fed a HF diet, the organic anion-transporting protein (Oatp) 1, Mrp3, CYP1A, CYP2C, UDP-glucuronosyltransferase (UGT) 1A1, and UGT1A5 protein levels were moderately decreased and the Oatp2, CYP3A, and UGT2B1 protein levels were markedly suppressed. No significant difference in the baseline level of Oatp1, Oatp2, Mrp2, Mrp3, Mdr1b, CYP1A, CYP2C, CYP3A, UGT1A1, UGT1A5, or UGT2B1 protein was found between the standard diet- and HF diet-fed groups. In addition, the mRNA levels of Oatp2, CYP2C11, and CYP3A1/2 were markedly decreased in HF diet-fed and fluvastatin-treated rats. There was no significant difference in the glucuronidation activities against fluvastatin among the four groups. In liver cell nuclei, levels of constitutive androstane receptor, pregnane X receptor, and hepatocyte nuclear factor 4alpha proteins were decreased in fluvastatin-treated HF diet-fed rats, which correlated with the decrease in Oatp2, CYP2C, and CYP3A. Taken together, these results indicate that nutritional status may influence adverse effects of fluvastatin by increasing systemic exposure through modulation of hepatic uptake and elimination. PMID- 20587624 TI - Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in vivo. AB - AIMS: Liver X receptor (LXR) is a nuclear receptor regulating cholesterol metabolism. Liver X receptor has also been shown to exert anti-proliferative and anti-inflammatory properties. In this study, we evaluated the effect of LXR activation on cardiac hypertrophy in vitro and in vivo. METHODS AND RESULTS: Treatment with the synthetic LXR agonist T0901317 (T09) attenuated the hypertrophic response of cultured cardiomyocytes to endothelin-1 almost to control levels. siRNA interference showed that this effect was indeed LXR specific. To corroborate these findings in vivo, abdominal aortic constriction (AC) was used as a pressure overload model to induce cardiac hypertrophy in wild type and LXR-alpha-deficient (LXR-alpha(-/-)) mice. In wild-type mice, T09 treatment resulted in a decrease of cardiac wall thickening 4 and 7 weeks after AC. Also, after 7 weeks of AC, mean arterial blood pressure and left ventricular weight/body weight (LVW/BW) ratios were decreased in T09 treated mice. These effects were not observed in LXR-alpha(-/-) mice, indicating that the beneficial effect of LXR activation on cardiac hypertrophy is attributable to the LXR-alpha isoform. T09 induced robust cardiac expression of metabolic genes which are downstream of LXR-alpha, such as SREBP-1c, ABCA1, and ABCG1. CONCLUSION: Together these results indicate that LXR exerts salutary effects in cardiac hypertrophy, possibly via metabolic remodelling. PMID- 20587625 TI - Editorial. Health promotion: Nairobi call for action. PMID- 20587627 TI - Health strategies and reservoirs of knowledge among adolescents in Denmark. AB - This article presents selected results of qualitative research into perceptions of health among adolescents. Pupils (N = 108) in the age 13-15 years from nine schools in four different municipalities in Denmark have been interviewed. An analytic strategy that combines knowledge research with systems theory is developed and used for the empirical analyses. The conclusions are focused on health-identities and health-strategies. Young people live their lives 'here and now' and it is hard for them to imagine how damaging the consequences of not taking risk-factors seriously can be. They cannot really relate to the diseases and it is therefore difficult for them to actively affect the different determinants. The adolescents feel that a lot of information and teaching is being directed towards them. They face an abundance of communication about health and information directed at their presumed risk-behaviour. They often experience saturation and lose both interest and focus. They reject patronizing or negative knowledge and generally express a desire to know more about the things that make life fun and positive. They feel that the knowledge directed at them must be more concrete and personally relevant for them. Finally, the adolescents are aware that they are influenced by their friends both positively and negatively. Indeed, they are concerned about the way they are being taught about health in school and desirous to learn more. PMID- 20587626 TI - School-based physical education programs: evidence-based physical activity interventions for youth in Latin America. AB - This article focuses on results of the systematic review from the Guide for Useful Interventions for Activity in Latin America project related to school based physical education (PE) programs in Latin America. The aims of the article are to describe five school-based PE programs from Latin America, discuss implications for effective school-based PE recommendations, propose approaches for implementing these interventions, and identify gaps in the research literature related to physical activity promotion in Latin American youth. Following the US Community Guide systematic review process, five school-based PE intervention studies with sufficient quality of design, execution and detail of intervention and outcomes were selected for full abstraction. One study was conducted in Brazil, two studies were conducted in Chile and two studies were conducted on the US/Mexico border. While studies presented assorted outcomes, methods and duration of interventions, there were consistent positive increases in physical activity levels for all outcomes measured during PE classes, endurance and active transportation to school in all three randomized studies. Except for one cohort from one study, the non-randomized studies showed positive intervention effects for moderate and vigorous physical activity levels during PE classes. The core elements of these five interventions included capacity building and staff training (PE specialists and/or classroom teachers); changes in the PE curricula; provision of equipment and materials; and adjustment of the interventions to specific target populations. In order to translate the strong evidence for school-based PE into practice, systematic attention to policy and implementation issues is required. PMID- 20587628 TI - How does socio economic position link to health behaviour? Sociological pathways and perspectives for health promotion. AB - Socio economic inequalities in adult health behaviour are consistently observed. Despite a well-documented pattern, social determinants of variations in health behaviour have not been sufficiently clarified. This article therefore presents sociological pathways to explain the existing inequalities in health behaviour. At a micro level, control beliefs have been part of several behavioural theories. We suggest that these beliefs might bridge the gap between sociology and psychology by emphasising their roots in fundamental socio-economic environments. At a meso level, social networks and support have not been explicitly considered as behavioural determinants. This contribution states that these social factors influence health behaviour while being unequally distributed across society. At a macro level, characteristics of the neighbourhood environment influence health behaviour of its residents above and beyond their individual background. Providing further opportunity for policy makers, it is shown that peer and school context equalise inequalities in risky behaviour in adolescence. As a conclusion, factors such as control expectations, social networks, neighbourhood characteristics, and school context should be included as strategies to improve health behaviour in socially disadvantaged people. PMID- 20587629 TI - Exploring facilitators and barriers to individual and organizational level capacity building: outcomes of participation in a community priority setting workshop. AB - This article explores facilitators and barriers to individual and organizational capacity to address priority strategies for community-level chronic disease prevention. Interviews were conducted with a group of participants who previously participated in a community priority-setting workshop held in two Alberta communities. The goal of the workshop was to bring together key community stakeholders to collaboratively identify action strategies for preventing chronic diseases in their communities. While capacity building was not the specific aim of the workshop, it could be considered an unintended byproduct of bringing together community representatives around a specific issue. One purpose of this study was to examine the participants' capacity to take action on the priority strategies identified at the workshop. Eleven one-on-one semi-structured interviews were conducted with workshop participants to examine facilitators and barriers to individual and organizational level capacity building. Findings suggest that there were several barriers identified by participants that limited their capacity to take action on the workshop strategies, specifically: (i) organizations' lack of priorities or competing priorities; (ii) priorities secondary to the organizational mandate; (iii) disconnect between organizational and community priorities; (iv) disconnect between community organization priorities; (v) disconnect between organizations and government/funder priorities; (vi) limited resources (i.e. time, money and personnel); and, (vii) bigger community issues. The primary facilitator of individual capacity to take action or priority strategies was supportive organizations. Recognition of these elements will allow practitioners, organizations, governments/funders, and communities to focus on seeking ways to improve capacity for chronic disease prevention. PMID- 20587630 TI - Health promotion through rediscovery of one's sensibilities of health: the Lifemap and WIFY Methods. AB - Japanese people place a high priority on maintaining social harmony and conforming with what we perceive to be mainstream thought and opinion. These social norms present challenges for developing health promotion policies and programs that value individual uniqueness and individual sensibilities about health. To address this challenge, over the past 20 years the author has developed two 'write-and-share' methods - Life-map and WIFY (What Is Important For you) to allow participants to reflect and rediscover their own and one another's feelings about daily life and health. This article summarizes his experiences using these methods and discusses their possible usefulness in other Asian societies. PMID- 20587631 TI - Arguing for a centralized coordination solution to the public-private partnership explosion in global health. AB - Public-private partnerships are widely seen as the future of global health; the only realistic option for achieving results in social challenges like infectious disease, because of the needed innovation, expertise and financing that a multiplicity of stakeholders can together provide. Yet, harnessing that potential requires finding a harmony among the drastically different incentive structures and internal cultures of profit-based companies, public institutions and humanitarian initiatives. While public-private partnerships have accomplished the important task of mobilizing new funding for global health, their growing dominance in governance raises questions about their effectiveness, but in particular, about the problem of accountability posed by their structure. This commentary aims to initiate a discussion around the coordination problem that exists with the employment of partnerships in global health and argues that the remedy is to apply a public goods theory approach to centralizing what is currently a fractured, inefficient, and potentially detrimental system. PMID- 20587632 TI - Developing a national physical activity plan: the Kuwait example. AB - A rapid increase in economic well-being and urbanization in Kuwait have been accompanied by profound changes in lifestyle, including low levels of physical activity in all population groups. These changes have contributed to a high prevalence of overweight and obesity and to the escalation of the non communicable disease rates, particularly coronary heart disease, stroke, hypertension and diabetes. The evolution of physical activity promotion, internationally, and a series of related meetings in Kuwait and neighboring countries, have started to generate an awareness among health authorities of the importance of physical activity in health promotion and disease prevention. A National Physical Activity Committee has been formed to design and implement a National Physical Activity Plan, which could also serve as a model for other countries. The authors describe the background and principles behind the development of the National Plan, summarize a template based upon the Kuwait experience and share the lessons learned from these efforts. PMID- 20587634 TI - [Increasing the rate of exclusive maternal breast feeding in the urban community of Niamey, in Niger: proposals of health professionals]. PMID- 20587635 TI - [The Ottawa Charter drawn up in 2009? a sixth axis in favor of research]. PMID- 20587637 TI - [Effective educational program for the training of community agents of health volunteers in Lima]. PMID- 20587587 TI - Effects of medical therapies on retinopathy progression in type 2 diabetes. AB - BACKGROUND: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.) PMID- 20587639 TI - Muscle injuries and PRP: what does the science say? PMID- 20587640 TI - Descriptive profile of scapulothoracic position, strength and flexibility variables in adolescent elite tennis players. AB - STUDY DESIGN: Descriptive study, cross-sectional design. BACKGROUND: Tennis requires repetitive overhead movement patterns that can lead to upper extremity injury. The scapula plays a vital role in injury-free playing. Scapular dysfunction has been associated with shoulder injury in the overhead athlete. OBJECTIVES: The purpose of this study was to describe variables regarding scapular position, muscle strength and flexibility in young elite tennis players. METHODS: Thirty-five adolescent Swedish elite tennis players (19 boys, aged 13.6 (+/-1.4) years, 16 girls, aged 12.6 (+/-1.3) years), selected on the basis of their national ranking, underwent a clinical screening protocol consisting of: scapular upward rotation at several angles of arm elevation; isometric scapular muscle strength; and anthropometric measurement of pectoralis minor (PM) length. RESULTS: The players showed significantly more scapular upward rotation on their dominant side (p<0.001). For both genders, upper trapezius (p=0.003) and serratus anterior (p=0.01) strength was significantly greater on the dominant side, whereas middle and lower trapezius strength showed no side differences. PM was shorter on the dominant side (p<0.001), and in the female players (p=0.006) compared with the boys. CONCLUSION: These results indicate some sports-related adaptations of young tennis players on their dominant side at the scapulothoracic level to exposure to their sport. These data may assist the clinician in the prevention and rehabilitation of sport-specific injuries in adolescent tennis players. PMID- 20587641 TI - A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--part 10. PMID- 20587642 TI - Recent trends in tuberculosis in children in London. AB - BACKGROUND: Childhood tuberculosis (TB) represents a sentinel event of recent transmission and is an indication of the effectiveness of prevention and control interventions. We analysed the trends in the epidemiology of TB in children in London aged 0-14 years between 1999 and 2006. METHODS: Data were extracted from the Enhanced TB Surveillance System. RESULTS: Between 1999 and 2006, there were 1370 cases of TB in children. Incidence was higher in older children and in girls. The incidence rates in London Boroughs varied from 0.4/100,000 to 32.7/100,000. Between 1999 and 2006, Black-Africans comprised 49.2% of all TB cases in children, children from the Indian Subcontinent 21.8% and Whites 8.5%. The proportion of cases born in the UK averaged 52.4% during this period. Of non UK-born children 79.3% were diagnosed with TB within 5 years of entry. CONCLUSIONS: Ethnicity, country of birth and age are important risk factors for development of. With an overall TB incidence in London exceeding 40/100,000, universal BCG immunization of all neonates should be considered across all London boroughs. PMID- 20587644 TI - Localized development of knee osteoarthritis can be predicted from MR imaging findings a decade earlier. AB - PURPOSE: To define localized development of knee osteoarthritis (OA) that arises from anterior cruciate ligament (ACL) and meniscal injuries identified at magnetic resonance (MR) imaging performed a decade ago and the subsequent management of those findings in patients with subacute knee symptoms. MATERIALS AND METHODS: The present study was approved by local medical ethics review boards, and written informed consent was obtained. Three hundred twenty-six patients (mean age, 42 years; 108 female) from a previously reported series of 855 patients were followed up with regard to the effect of MR imaging-guided treatment for subacute knee problems. The mean follow-up period was 10 years. Initial findings and treatment were compared with the follow-up radiograph and 3.0-T MR image findings. Odds ratios (ORs), with corresponding 95% confidence intervals, were used to identify the effects between variables. RESULTS: Patients with ACL ruptures had an increased risk of developing joint space narrowing (JSN), cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts medially or laterally (OR, 2.4-9.8). Patients with medial meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, and bone marrow lesions medially (OR, 2.0-15.3). Patients with lateral meniscal tears had an increased risk of developing JSN, cartilaginous defects, osteophytes, bone marrow lesions, and subchondral cysts laterally (OR, 2.1-10.5). Meniscectomy had no effect on the risk of developing OA. CONCLUSION: Localized knee OA developed from risk factors identified from the findings of MR imaging performed a decade ago in patients with subacute knee symptoms and did not depend on the surgical treatment of those findings. PMID- 20587643 TI - Effect of advanced imaging technology on how biopsies are done and who does them. AB - PURPOSE: To assess national levels and trends in utilization of biopsy procedures during the past decade and investigate the relative roles of biopsy approaches (open, endoscopic, and percutaneous) and physician specialties. MATERIALS AND METHODS: Institutional review board approval was not necessary because only public domain data were used. Aggregated Medicare claims data were used to determine utilization of biopsies performed in 10 anatomic regions from 1997 to 2008. Utilization levels according to biopsy approach and anatomic region were calculated. Trends in the relative utilization of percutaneous needle biopsy (PNB) and imaging-guided percutaneous biopsy (IGPB) were assessed. The relative roles of radiologists and nonradiologists in the performance of all biopsies, PNBs, and IGPBs were evaluated. RESULTS: Biopsy procedures with all approaches increased from 1380 to 1945 biopsies per 100,000 Medicare enrollees between 1997 and 2008, which represents a compound annual growth rate (CAGR) of 3%. Utilization of non-PNBs fell, while the absolute level and relative share of PNBs increased. In 2008, 67% of all biopsies were performed by using a percutaneous route. IGPB as a percentage of all PNBs increased over time in the regions for which data were available. Radiology was the leading specialty providing biopsy services. The total number of biopsies performed by radiologists increased at a CAGR of 8%, and radiologists' share of all biopsies increased from 35% to 56%. CONCLUSION: During the past decade, there was continuing substitution away from invasive approaches and non-imaging-guided percutaneous approaches in favor of PNBs and IGPBs, likely related to increasing use of advanced imaging modalities for biopsy guidance. Consequently, radiologists are performing an increasing share of biopsies across all anatomic regions. PMID- 20587645 TI - Site-specific modification of anti-angiogenesis peptide HM-3 by polyethylene glycol molecular weight of 20 kDa. AB - HM-3, an RGD modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory. Its robust inhibitory effects on endothelial cell migration and tumour growth have been demonstrated by in vivo and in vitro activity assays. However, the drug has relatively short half-life in vivo. For the purpose of prolonging HM-3 half-life and retaining the safety and efficacy of the peptide, the study chose methoxy-polyethylene glycol-Succinimidyl Carbonate (SC-mPEG, molecular weight 20 kDa, named SC-mPEG(20k)) to specifically modify its N terminus. Compared with HM-3, the site-specific mono-PEGylated peptide PEG(20k)-HM-3 was shown the same activity in the inhibition of B16F10 tumour in vivo (the inhibitory effect of PEG(20k)-HM-3, HM-3 and Taxol were 44.35, 39.68%, respectively), while the frequency of drug-administering reduced from twice a day to once every 3 days. Its rate of in vitro degradation in serum was markedly reduced (72.78% could still be detected after 132 h). Histochemistry and immunohistochemistry analysis showed that both HM-3 and PEG(20k)-HM-3 induced large areas of continuous necrosis within tumours and significantly reduced the vessel density compared to control. It might be a breakthrough in PEG modification field to modify a small peptide with a large PEG and reach a good result. PMID- 20587646 TI - Essential covalent linkage between the chymotrypsin-like domain and the extra domain of the SARS-CoV main protease. AB - The main protease of the coronavirus causing severe acute respiratory syndrome performs proteolytic processing of the viral polyproteins. The active form of the enzyme is a homodimer with each subunit consisting of three structural domains. Domains I and II, hosting the complete catalytic machinery, constitute the N terminal chymotrypsin-like folding scaffold and connect to the extra C-terminal domain III by a long loop. Previously, the domain III-truncated enzyme was demonstrated to fold independently into an intact chymotrypsin-like fold, but it showed no enzyme activity. To further delineate the structure-function relationships of the domain III and the long loop, we generated some truncated and mutated M(pro) forms bearing various combinations of the loop with other structural parts of the enzyme. Their conformational and association properties were investigated in detail. Far-ultraviolet circular dichroism (CD) measurements revealed that these fragments could fold independently. The secondary, tertiary and quaternary structures of these mixtures were monitored by CD, fluorescence spectroscopy and analytical ultracentrifugation. However, no enzyme activity was observed for any mutant or mixtures. These observations indicate that the covalent linkage between the chymotrypsin like and the extra domain is essential for enzymatic activity of the main coronavirus protease and for the integrity of its quaternary structure. PMID- 20587647 TI - A novel thermostable carboxylesterase from Geobacillus thermodenitrificans: evidence for a new carboxylesterase family. AB - A novel gene encoding an esterase from Geobacillus thermodenitrificans strain CMB A2 was cloned, sequenced and functionally expressed in Escherichia coli M15. Sequence analysis revealed an open reading frame of 747 bp corresponding to a polypeptide of 249 amino acid residues (named EstGtA2). After purification, a specific activity of 2.58 U mg(-1) was detected using p-NP caprylate (C8) at 50 degrees C and pH 8.0 (optimal conditions). The enzyme catalyses the hydrolysis of triglycerides (tributyrin) and a variety of p-nitrophenyl esters with different fatty acyl chain length (C4-C16). The enzyme has potential for various industrial applications since it is characterized by its activity under a wide range of pH, from 25 to 65 degrees C. Using Geobacillus stearothermophilus Est30 esterase structure as template, a model of EstGtA2 was built using ESyPred3D. Analysis of this structural model allowed identifying putative sequence features that control EstGtA2 enzymatic properties. Based on sequence properties, multiple sequence comparisons and phylogenetic analyses, this enzyme appears to belong to a new family of carboxylesterases. PMID- 20587648 TI - A comparative study of the effective radiation doses from cone beam computed tomography and plain radiography for sialography. AB - OBJECTIVES: As a first step in developing a protocol for multidimensional sialography using cone beam CT (CBCT), the objective of this study was to compare the effective radiation doses from sialography of the parotid and submandibular glands using plain radiography and CBCT. METHODS: The effective doses were calculated from dose measurements made at 25 selected locations in the head and neck of a radiation analogue dosimeter (RANDO) phantom, using International Commission on Radiological Protection 2007 tissue weighting factors. RESULTS: The effective dose (E) changed in relationship to changes in CBCT field of view (FOV), peak kilovoltage (kVp) and milliamperage (mA). Specifically, E decreased from a maximum of 932 microSv (30 cm FOV, 120 kVp, 15 mA) to 60 microSv (15 cm FOV, 80 kVp, 10 mA) for a parotid gland study and to 148 microSv (15 cm FOV, 80 kVp, 10 mA) for a submandibular study. The collective series of plain radiographs made during sialography of the parotid and submandibular glands yielded effective doses of 65 microSv and 156 microSv, respectively. The plain parotid gland series included one panoramic, two anterior-posterior skull and four lateral skull radiographs, whereas the submandibular gland series included one panoramic, one standard mandibular occlusal and four lateral skull radiographs. CONCLUSION: The effective doses from CBCT examinations centred on the parotid and submandibular glands were similar to those calculated for plain radiograph sialography when a 15 cm FOV was chosen in combination with exposure conditions of 80 kVp and 10 mA. PMID- 20587649 TI - Evaluation of demineralized bone and bone transplants in vitro and in vivo with cone beam computed tomography imaging. AB - OBJECTIVES: The objective of this study was to determine the ability of two flat panel cone beam CT (CBCT) devices to identify demineralized bone and bone transplants in vivo and in vitro. METHODS: Datasets from patients with autologous bone grafts (n = 9, KaVo 3DeXam (KaVo, Biberach, Germany); n = 38, Accuitomo 40 (Morita, Osaka, Japan)) were retrospectively evaluated. Demineralized and non demineralized porcine cancellous bone blocks were examined with the two CBCT devices. A SawBone skull (Pacific Research Laboratories, Vashon, WA) was used as a positioning tool for the bone blocks. Descriptive evaluation and image quality assessment were conducted on the KaVo 3DeXam data (voxel size 0.3 mm) using the OsiriX viewer as well as on the Morita Accuitomo data (voxel size 0.25 mm) using proprietary viewer software. RESULTS: Both in vivo and in vitro, the descriptive analysis of the images of the two devices showed well-visualized bone transplants with clearly defined cancellous bones and well-defined single bone trabeculae in all cross-sections. In vitro, demineralized samples showed lower radiographic opacity but no significant loss of quality compared with fresh bone (P = 0.070). Single cancellous bone trabeculae were significantly better visualized with the Morita 3D Accuitomo device than with the KaVo 3DeXam device (P = 0.038). CONCLUSION: Both the KaVo 3DeXam and Morita 3D Accuitomo devices produce good quality images of cancellous bones in in vivo remodelling as well as after in vitro demineralization. PMID- 20587650 TI - Diagnostic performance of magnetic resonance imaging for detecting osseous abnormalities of the temporomandibular joint and its correlation with cone beam computed tomography. AB - OBJECTIVE: With cone beam CT (CBCT) as the reference standard, the objective of this study was to determine the diagnostic accuracy of MRI for assessing osseous abnormalities of the temporomandibular joint (TMJ). METHODS: 106 TMJs from 55 patients with temporomandibular disorder were examined by CBCT and MRI. CBCT images were evaluated by two experienced oral radiologists with regard to the presence or absence of each of the following eight types of osseous abnormalities: Type 1, destructive and erosive osseous changes of the condyle; Type 2, flattening of the articular surface of the condyle; Type 3, deformity of the condyle; Type 4, sclerosis of the condyle; Type 5, osteophyte formation; Type 6, ankylosis; Type 7, erosion of the articular fossa and/or eminence; and Type 8, sclerosis of the articular fossa and/or eminence. For detection of these osseous abnormalities by MRI, proton density-weighted images and T(2) weighted images were evaluated independently by three observers. Using CBCT findings as the reference standard, the diagnostic performance of MRI for detecting various types of osseous abnormalities was evaluated by calculating its sensitivity and specificity. RESULTS: Out of 106 joints, CBCT revealed Types 1, 2, 3, 4, 5, 6, 7 and 8 abnormalities in 25, 19, 26, 20, 14, 5, 19 and 22 joints, respectively. The mean sensitivities of MRI among the three observers for detecting Types 1, 2, 3, 4, 5, 6, 7 and 8 abnormalities were 61%, 30%, 82%, 40%, 48%, 34%, 61% and 41%, respectively, whereas the mean specificities were 86%, 92%, 91%, 95%, 84%, 98%, 89% and 91%, respectively. CONCLUSIONS: Although high specificity (84-98%) was obtained with MRI, this modality showed relatively low sensitivity (30-82%) for detecting osseous abnormalities of the TMJ. The value of MRI for the detection of TMJ osseous abnormalities is considered to be limited. PMID- 20587651 TI - Prevalence of ponticulus posticus in Indian orthodontic patients. AB - OBJECTIVES: The purpose of this study was to investigate the prevalence of complete ponticulus posticus in Indian orthodontic patients. METHODS: The presence and types of ponticuli posticus were investigated on 858 lateral cephalograms. RESULTS: Complete ponticulus posticus was found in 4.3% of the subjects studied with a male (5.33%) predominance over female in the population (3.76%). CONCLUSIONS: Ponticulus posticus is not a rare anomaly and the patient must be told of the implications and importance of detecting ponticulus posticus on a lateral cephalogram. This information can prove beneficial for the diagnosis of head and neck symptoms later. PMID- 20587652 TI - Assessment of bone mineral density in the jaws and its relationship to radiomorphometric indices. AB - OBJECTIVES: The aim of this study was to evaluate maxillary, mandibular and femoral neck bone mineral density using dual energy X-ray absorptiometry (DXA) and to determine any correlation between the bone mineral density of the jaws and panoramic radiomorphometric indices. METHODS: 49 edentulous patients (18 males and 31 females) aged between 41 and 78 years (mean age 60.2 +/- 11.04) were examined by panoramic radiography. Bone mineral density (BMD) of the jaws and femoral neck was measured with a DXA; bone mineral density was calculated at the anterior, premolar and molar regions of the maxilla and mandible. RESULTS: The mean maxillary molar BMD (0.45 g cm(-2)) was significantly greater than the maxillary anterior and premolar BMD (0.31 g cm(-2), P < 0.05). Furthermore, the mean mandibular anterior and premolar BMD (1.39 g cm(-2) and 1.28 g cm(-2), respectively) was significantly greater than the mean mandibular molar BMD (1.09 g cm(-2), P < 0.01). Although BMD in the maxillary anterior and premolar regions were correlated, BMD in all the mandibular regions were highly correlated. Maxillary and mandibular BMD were not correlated with femoral BMD. In addition, mandibular cortical index (MCI) classification, mental index (MI) or panoramic mandibular index (PMI) values were not significantly correlated with the maxillary and mandibular BMDs (P > 0.05). CONCLUSIONS: The BMD in this study was highest in the mandibular anterior region and lowest in the maxillary anterior and premolar regions. The BMD of the jaws was not correlated with either femoral BMD or panoramic radiomorphometric indices. PMID- 20587653 TI - Comparison of antegonial index, mental index, panoramic mandibular index and mandibular cortical index values in the panoramic radiographs of normal males and male patients with osteoporosis. AB - OBJECTIVE: The aim of the study was to compare the values of the antegonial index (AI), mental index (MI), panoramic mandibular index (PMI) and mandibular cortical index (MCI) in the panoramic radiographs of normal males and male patients with osteoporosis. METHODS: In panoramic radiographs obtained from 40 male individuals (20 normal and 20 with osteoporosis), the mean was calculated for MI, AI, PMI and MCI index values measured in the right and left mandibles. The MI, AI and PMI index values were evaluated using the paired t-test, and MCI values were analysed using the chi(2) test. RESULTS: MI (P < 0.001), AI (P < 0.01) and PMI (P < 0.05) values were significantly smaller in the group with osteoporosis; however, MCI (P > 0.05) was not significantly different. CONCLUSION: MI, PMI and AI values, as radiomorphometric indices, were found to be smaller among male patients with osteoporosis, compared with normal patients in this study. It is suggested that these indices, used as an ancillary method in the diagnosis of osteoporosis in women, could also be useful for male patients. Further studies, of larger groups are needed on this subject, including of the MCI, which in this study showed no significant difference. PMID- 20587654 TI - Biomonitoring of DNA damage and cytotoxicity in individuals exposed to cone beam computed tomography. AB - OBJECTIVES: The aim of the present study was to evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated buccal mucosa cells from adults following cone beam CT exposure. METHODS: A total of 19 healthy adults (10 men and 9 women) submitted to cone beam CT were included. RESULTS: No significant statistically differences (P > 0.05) in micronucleus frequency were seen before and after cone beam CT exposure. In contrast, the tomography was able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis and karyolysis (P < 0.05). CONCLUSION: In summary, these data indicate that cone beam CT may not be a factor that induces chromosomal damage, but it is able to promote cytotoxicity. PMID- 20587655 TI - A contrast correction method for dental images based on histogram registration. AB - Contrast correction is often required in digital subtraction radiography when comparing medical data acquired over different time periods owing to dissimilarities in the acquisition process. This paper focuses on dental radiographs and introduces a novel approach for correcting the contrast in dental image pairs. The proposed method modifies the subject images by applying typical registration techniques on their histograms. The proposed histogram registration method reshapes the histograms of the two subject images in such a way that these images are matched in terms of their contrast deviation. The method was extensively tested over 4 sets of dental images, consisting of 72 registered dental image pairs with unknown contrast differences as well as 20 dental pairs with known contrast differences. The proposed method was directly compared against the well-known histogram-based contrast correction method. The two methods were qualitatively and quantitatively evaluated for all 92 available dental image pairs. The two methods were compared in terms of the contrast root mean square difference between the reference image and the corrected image in each case. The obtained results were also verified statistically using appropriate t-tests in each set. The proposed method exhibited superior performance compared with the well-established method, in terms of the contrast root mean square difference between the reference and the corrected images. After suitable statistical analysis, it was deduced that the performance advantage of the proposed approach was statistically significant. PMID- 20587656 TI - Unusual radiographic appearance of ossifying fibroma in the left mandibular angle. AB - Ossifying fibroma is usually a unilocular lesion with a well-defined, thinly corticated margin radiographically, although various patterns have been noted. The patient was a 27-year-old woman with a painless radiolucent lesion demonstrated on panoramic radiography to involve the root-apex area of the left lower second and third molars. Radiographically, the lesion had some features of a benign tumour, such as an odontogenic myxoma. However, the deep invaginations towards the interalveolar septa suggested a simple bone cyst, whereas the irregular margin and lack of expansion or mandibular canal displacement were consistent with a malignant lesion. A hard tissue component was confirmed only by soft-tissue mode CT. Although this lesion was histopathologically diagnosed as ossifying fibroma, the conflicting imaging findings were challenging and very intriguing. PMID- 20587657 TI - In vitro comparison of digital and conventional bitewing radiographs. PMID- 20587660 TI - p53-independent induction of G1 arrest and p21WAF1/CIP1 expression by ascofuranone, an isoprenoid antibiotic, through downregulation of c-Myc. AB - Ascofuranone has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we study the effects of ascofuranone on cell cycle progression in human cancer cells and find that ascofuranone induces G(1) arrest without cytoxicity with upregulation of p53 and p21(WAF1/CIP1) while downregulating c-Myc and G(1) cyclins. Chromatin immunoprecipitation assay and RNA interference studies with cells deficient in p53 and p21 show that ascofuranone induces p21(WAF1/CIP1) expression and subsequent G(1) arrest through the release of p21(WAF1/CIP1) promoter from c-Myc-mediated transcriptional repression, independent of p53. Ascofuranone-induced p21(WAF1/CIP1) associates with CDK2 and prevents CDK2-cyclin E complex formation, leading to the inactivation of E2F transcriptional activity. These results suggest that ascofuranone upregulates p21(WAF1/CIP1) through p53 independent suppression of c-Myc expression, leading to cytostatic G(1) arrest. Thus, ascofuranone represents a unique natural antitumor compound that targets c Myc independent of p53. PMID- 20587661 TI - Radiosensitization and stromal imaging response correlates for the HIF-1 inhibitor PX-478 given with or without chemotherapy in pancreatic cancer. AB - Growing tumors are hypoxic and respond to microenvironmental stress through increased expression of the hypoxia inducible factor-1alpha (HIF-1alpha) transcription factor, resulting in an adaptive switch to glycolytic metabolism, angiogenic signaling, survival, and metastasis. HIF-1alpha expression is associated with tumor resistance to cytotoxic therapy and inferior patient outcomes. Pancreatic cancer is the most hypoxic of all solid tumors and remains refractory to current chemoradiotherapy. We have seen nuclear HIF-1alpha in 88% of human pancreatic ductal carcinoma but in only 16% of normal pancreas. Stroma adjacent to the pancreatic ductal carcinoma also showed HIF-1alpha in 43% of cases. We investigated the novel selective HIF-1alpha inhibitor PX-478 on in vitro and in vivo radiation response of human pancreatic cancer models. Inhibition of HIF-1alpha by PX-478 increased cell killing by radiation. In mice with Panc-1, CF-PAC-1, or SU.86.86 pancreatic xenografts, concurrent administration of PX-478 potentiated the antitumor effects of fractionated radiation, with or without combined treatment with 5-fluorouracil or gemcitabine. Alternative sequencing of PX-478 with fractionated radiotherapy suggests optimal radiosensitization with concurrent or neoadjuvant administration of drug. Early tumor responses to combined PX-478/radiation treatment could be rapidly and repeatedly quantified by vascular imaging biomarkers. Dual-tracer dynamic contrast enhanced-magnetic resonance imaging and ultrasound imaging discriminated response to combined treatment prior to detection of differences in anatomic tumor size at 10 days posttreatment. Therefore, PX-478 is a mechanistically appealing and potentially clinically relevant enhancer of pancreatic cancer radiosensitivity, inhibiting tumor and stromal HIF-1 proangiogenic signaling and reducing the innate radiation resistance of hypoxic tumor cells. PMID- 20587662 TI - ABT-737 overcomes resistance to immunotoxin-mediated apoptosis and enhances the delivery of pseudomonas exotoxin-based proteins to the cell cytosol. AB - Pseudomonas exotoxin (PE)-based immunotoxins (antibody-toxin fusion proteins) have achieved frequent complete remissions in patients with hairy cell leukemia but far fewer objective responses in other cancers. To address possible mechanisms of resistance, we investigated immunotoxin activity in a model system using the colon cancer cell line, DLD1. Despite causing complete inhibition of protein synthesis, there was no evidence that an immunotoxin targeted to the transferrin receptor caused apoptosis in these cells. To address a possible protective role of prosurvival Bcl-2 proteins, the BH3-only mimetic, ABT-737, was tested alone or in combination with immunotoxins. Neither the immunotoxin nor ABT 737 alone activated caspase 3, whereas the combination exhibited substantial activation. In other epithelial cell lines, ABT-737 enhanced the cytotoxicity of PE-related immunotoxins by as much as 20-fold, but did not enhance diphtheria toxin or cycloheximide. Because PE translocates to the cytosol via the endoplasmic reticulum (ER) and the other toxins do not, ABT-737-mediated effects on the ER were investigated. ABT-737 treatment stimulated increased levels of ER stress response factor, ATF4. Because of its activity in the ER, ABT-737 might be particularly well suited for enhancing the activity of immunotoxins that translocate from the ER to the cell cytosol. PMID- 20587663 TI - Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. AB - The recent discovery of an acquired activating point mutation in JAK2, substituting valine at amino acid position 617 for phenylalanine, has greatly improved our understanding of the molecular mechanism underlying chronic myeloproliferative neoplasms. Strikingly, the JAK2(V617F) mutation is found in nearly all patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia and primary myelofibrosis. Thus, JAK2 represents a promising target for the treatment of myeloproliferative neoplasms and considerable efforts are ongoing to discover and develop inhibitors of the kinase. Here, we report potent inhibition of JAK2(V617F) and JAK2 wild type enzymes by a novel substituted quinoxaline, NVP-BSK805, which acts in an ATP competitive manner. Within the JAK family, NVP-BSK805 displays more than 20-fold selectivity towards JAK2 in vitro, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation in JAK2(V617F)-bearing cells, with concomitant suppression of cell proliferation and induction of apoptosis. In vivo, NVP-BSK805 exhibited good oral bioavailability and a long half-life. The inhibitor was efficacious in suppressing leukemic cell spreading and splenomegaly in a Ba/F3 JAK2(V617F) cell-driven mouse mechanistic model. Furthermore, NVP-BSK805 potently suppressed recombinant human erythropoietin-induced polycythemia and extramedullary erythropoiesis in mice and rats. PMID- 20587664 TI - Identification of internalizing human single-chain antibodies targeting brain tumor sphere cells. AB - Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor for which there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease, and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive medium and exhibits enhanced tumor-initiating ability and resistance to therapy. We report here the identification of internalizing human single-chain antibodies (scFv) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly, as well as scFvs that target the CD133-positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv, and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular nonselective medium. Taken together, these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library, which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment. PMID- 20587666 TI - The superparamagnetic nanoparticles carrying the E1A gene enhance the radiosensitivity of human cervical carcinoma in nude mice. AB - To explore the effects of early region 1A (E1A) carried by superparamagnetic dextran iron oxide nanoparticles (SDION) on the radiosensitivity of human cervical cancer. The xenograft mice with cervical cancer received weekly intratumoral SDION-E1A injection and a subsequent 50-Gy irradiation. The weekly relative tumor volume and the final tumor volume were compared among different experimental groups. p53 and human epidermal growth factor receptor-2 (HER-2)/Neu expression in final tumor tissue was detected by reverse transcription-PCR and Western blot. The relative tumor volume and the final tissue volume in the SDION E1A group was significantly smaller than that in Sham and SDION-Vector groups at each time points after irradiation (P < 0.05). Exogenous E1A expression by SDION delivery significantly increased p53 expression, but inhibited HER-2/Neu expression in tumor tissue (P < 0.05). The intratumoral delivery of exogenous E1A carried by SDION increases p53 expression but inhibits HER-2/neu expression, and enhances the radiosensitivity of human cervical cancer in xenograft mice. PMID- 20587665 TI - MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo. AB - Papillary thyroid carcinomas (PTC) are the most common type of thyroid malignancy. Most PTC carry one of the two mutations, RET/PTC rearrangement or BRAF mutation. Both mutations are able to activate the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling transduction pathway leading to cellular proliferation, differentiation, and apoptosis. PD0325901 is a specific MEK1/2 inhibitor and therefore is a promising drug to treat thyroid cancers with either RET/PTC or BRAF mutation. In this study we tested the effects of PD0325901 on PTC cells harboring either mutation in vitro by growth curves and Western blots and in vivo using a murine orthotopic xenograft model. We found that 50% growth inhibition (GI(50)) by PD0325901 was 11 nmol/L for the PTC cells with the RET/PTC1 rearrangement and 6.3 nmol/L for PTC cells with a BRAF mutation, with both concentrations readily achievable in serum. After 1 week of oral administration of PD0325901 (20-25 mg/kg/day) in mice, no tumor growth was detected in mice inoculated with PTC cells bearing a BRAF mutation. For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor was reduced by 58% as compared with controls. In conclusion, our data suggested that PTC cells carrying a BRAF mutation were more sensitive to PD0325901 than were PTC cells carrying the RET/PTC1 rearrangement. Our findings support the clinical evaluation of PD0325901 for patients with PTC and potentially other carcinomas with BRAF mutations. PMID- 20587667 TI - Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. AB - Selumetinib (AZD6244; ARRY-142886) is a tight-binding, uncompetitive inhibitor of mitogen-activated protein kinase kinases (MEK) 1 and 2 currently in clinical development. We evaluated the effects of selumetinib in 31 human breast cancer cell lines and 43 human non-small cell lung cancer (NSCLC) cell lines to identify characteristics correlating with in vitro sensitivity to MEK inhibition. IC(50) <1 micromol/L (considered sensitive) was seen in 5 of 31 breast cancer cell lines and 15 of 43 NSCLC cell lines, with a correlation between sensitivity and raf mutations in breast cancer cell lines (P = 0.022) and ras mutations in NSCLC cell lines (P = 0.045). Evaluation of 27 of the NSCLC cell lines with Western blots showed no clear association between MEK and phosphoinositide 3-kinase pathway activation and sensitivity to MEK inhibition. Baseline gene expression profiles were generated for each cell line using Agilent gene expression arrays to identify additional predictive markers. Genes associated with differential sensitivity to selumetinib were seen in both histologies, including a small number of genes in which differential expression was common to both histologies. In total, these results suggest that clinical trials of selumetinib in breast cancer and NSCLC might select patients whose tumors harbor raf and ras mutations, respectively. PMID- 20587669 TI - Randomized controlled trial of mammography intervention in insured very low income women. AB - BACKGROUND: The expectation that insurance coverage mitigates health disparities and equalizes use of healthcare assumes that services are equally accessed; however, the insured low-income target population in this research had a mammography rate of 23.4%, well below the general population. Our objective was to determine the most effective intervention to improve mammography use in low income women insured by a managed care organization (MCO). METHODS: The study was a randomized controlled trial. Participants were 2,357 women noncompliant with screening mammography randomly assigned to one of three groups: control (n = 786) received usual care; simple intervention (n = 785) received prompt letter from the MCO medical director; and stepwise intervention (n = 786) received the same prompt letter from the MCO; if noncompliant, a second prompt letter from their primary care physician and, if still noncompliant, counseling from lay health workers. Outcome was completion of screening mammography extracted from medical records. RESULTS: Screening rates were 13.4% for the control, 16.1% for the simple intervention, and 27.1% for the stepwise intervention. Compared with the control, the primary care physician letter in the stepwise intervention increased the likelihood of screening by 80% [Relative Risk (RR) = 1.80; P < 0.001], and counseling tripled the likelihood of screening (RR = 3.11; P < 0.001). CONCLUSIONS: Compared with the control and simple intervention, a stepwise intervention to increase mammography is effective in a target population of hard to-reach, low-income, insured women. IMPACT: The research provides evidence for the impact of stepwise interventions to improve cancer screening in low-income insured populations, although the screening rates remain well below those of the general population. PMID- 20587668 TI - Silencing of integrated human papillomavirus-16 oncogenes by small interfering RNA-mediated heterochromatization. AB - Double-stranded RNAs or small interfering RNAs (siRNA) targeting the promoters of genes are known to cause gene knockdown by a process known as transcriptional gene silencing (TGS). We screened multiple siRNAs homologous to one of the NF-1 binding sites in the human papillomavirus-16 (HPV-16) enhancer and identified one siRNA which causes specific TGS of the HPV-16 oncogenes E6 and E7 when transfected into two HPV-16-positive cell lines siHa and CaSki. This phenomenon was specific to the HPV-16 enhancer with no effect on the HPV-18 enhancer. TGS was associated with heterochromatization of the targeted region of the enhancer but no DNA methylation was noted during the time period studied. The choice of target in the enhancer was important as siRNAs differing by one or two bases showed no suppression of downstream gene expression. A low copy number enhancer associated transcript was detected in the cell lines studied and its level decreased significantly after treatment with the siRNA that caused TGS. This supports the RNA:RNA model described previously for TGS. This siRNA which causes simultaneous silencing of E6 as well as E7 oncogenes by an epigenetic mechanism might be useful as a therapeutic modality for HPV-16-positive cervical and other epithelial cancers. PMID- 20587670 TI - Methadone-induced rigid-chest syndrome after substantial overdose. AB - We report here the case of an infant who developed life-threatening rigid-chest syndrome after receiving an accidental overdose of methadone. The child responded to narcotic reversal. Pediatric physicians should be aware of this possible complication. PMID- 20587671 TI - Reduction in gastroenteritis with the use of pentavalent rotavirus vaccine in a primary practice. AB - OBJECTIVES: Pentavalent rotavirus (RV) vaccine (RV5) was licensed in 2006 and recommended for routine childhood immunization. A significant decrease in the number of RV hospitalizations has been described. The objective of this study was to evaluate the effect of RV5 on acute gastroenteritis (AGE) seen in a primary practice. METHODS: In July 2004, surveillance was initiated among children who were younger than 5 years and seen in a large pediatric practice in New Orleans for those who presented AGE, as determined by International Classification of Diseases, Ninth Revision codes. Primary care physician office visits, emergency department visits, and hospital admissions were identified by review of records. RV testing was performed only on those who were seen at the hospital. RESULTS: Approximately 16,000 children who were younger than 5 years were followed in the practice during each year. For 2006-2007, 2007-2008, and 2008-2009, 11.1%, 40.3%, and 45.6% of age-eligible children, respectively, received > or =1 dose of RV5. As compared with 2004-2005 (before RV5), in 2007-2009, there was a significant decrease in all-cause AGE office visits (23%) and hospitalizations (50%). RV positive cases (emergency department visits or hospitalizations) decreased by 67%. The decrease in RV-positive cases was more evident among children who were younger than 2 years (81%), with a strong trend among those who were aged 2 to <5 years (41%). CONCLUSIONS: Increased use of RV5 in a pediatric practice was associated with fewer AGE office visits and hospitalizations. The reduction was specific for RV-positive AGE and seen among children who were targeted for immunization as well as older groups, suggesting a herd-immunity effect. PMID- 20587672 TI - Paternal smoking and childhood overweight: evidence from the Hong Kong "Children of 1997". AB - OBJECTIVE: This study examined, in a non-Western sociohistorical context, whether prenatal or postnatal secondhand smoke (SHS) exposure for children of nonsmoking mothers was associated with higher childhood BMI, and it clarified whether the observed associations were biologically mediated or socioeconomically confounded. METHODS: A total of 6710 and 6519 children of nonsmoking mothers (N = 7924) with BMI data at approximately 7 and approximately 11 years, respectively, from a population-representative (N = 8327), Hong Kong Chinese birth cohort ("Children of 1997"), born in April or May 1997, were included in the analysis. RESULTS: Compared with no SHS exposure, daily paternal smoking increased mean BMI z scores, but not height, at 7 years (difference: 0.10 [95% confidence interval: 0.02-0.19]) and at 11 years (difference: 0.16 [95% confidence interval: 0.07 0.26]), with adjustment for gender, birth order, socioeconomic position, mother's place of birth, breastfeeding, serious morbidity, and pubertal status. CONCLUSIONS: Our findings, although preliminary, suggest that the association of paternal smoking with child overweight might be biologically mediated. Given the known harms of smoking, reducing SHS exposure from conception as a precautionary action for childhood overweight might be warranted. PMID- 20587673 TI - Disparities in children's exposure to environmental tobacco smoke in the United States, 2007. AB - OBJECTIVES: This study examined racial/ethnic, socioeconomic, and geographic disparities in children's exposure to environmental tobacco smoke (ETS) or secondhand smoke in the home. METHODS: The 2007 National Survey of Children's Health (N = 90,853) was used to calculate the prevalence of children's exposure to ETS. State-level data on home smoking ban from the 2006-2007 Current Population Survey-Tobacco Use Supplement were used to supplement analyses. Logistic regression was used to estimate adjusted odds of exposure. RESULTS: In 2007, 7.6% of US children, or 5.5 million children, lived in households where someone smoked inside the home. The prevalence varied from a low of 1.1% for Utah and 1.9% for California to a high of 17.9% for West Virginia and 17.6% in Kentucky. After adjustment for sociodemographic factors, children in Ohio, West Virginia, Kentucky, and Pennsylvania had 12 times higher odds and those in Wisconsin, Missouri, Delaware, and the District of Columbia had 10 times higher odds of being exposed to ETS than children in Utah. Compared with children from higher socioeconomic backgrounds, Hispanic ethnicity, and non-English-speaking households, children from lower socioeconomic backgrounds had 7.3 to 10.6 times higher adjusted odds; non-Hispanic white, black, American Indian, and mixed-race children had 2.0 to 2.6 times higher odds; and children from English-speaking households had 4.1 times higher odds of ETS exposure. CONCLUSIONS: Considerable disparities exist in children's exposure to ETS, with geographic pattern strongly related to home smoking ban. Greater exposure to ETS among children in several states and disadvantaged socioeconomic groups is likely to exacerbate existing health disparities. PMID- 20587674 TI - Factors that influence the effectiveness of child protection teams. AB - OBJECTIVES: More than $55 million is spent on hospital-based child protection teams (CPTs) annually, but there is no consensus on what makes CPTs effective. The objective of this study was to create expert consensus on tasks that CPTs should perform and factors that contribute to effectiveness. METHODS: A modified Delphi approach was used to create expert consensus among professionals with experience working on or with hospital-based CPTs. Three initial rounds of surveys were conducted; a first round of open-ended questions generated topics related to CPT tasks and factors related to team effectiveness. A Likert scale (range: 1-7) determined rank. In the fourth round, participants ranked the top 5 variables associated with effectiveness. RESULTS: Twenty-six (90%) of 29 participants completed the first 3 rounds, and 20 (67%) completed the final ranking. Experts believed that CPTs should provide communication of findings to appropriate agencies (mean Likert score: 7.0), court testimony (7.0), medical consultations (6.9), multidisciplinary case review (6.6), and forensic interviews (6.0). CPT success should be determined by professionals who use CPT services (6.6) and CPT members (6.5). Variables that were ranked most often as critical to effectiveness included interdisciplinary collaboration (95% of participants), provision of resources (80%), and team collegiality (75%). Variables that were ranked as most detrimental included inadequate staffing (85%) and lack of collegiality (80%). CONCLUSIONS: A multidisciplinary team working in a collegial atmosphere seems to be the major key to CPT effectiveness. In addition to providing services, CPTs should focus on improving collegiality and interdisciplinary collaboration and should seek performance feedback from referring professionals and CPT members. PMID- 20587675 TI - Accuracy of MUAC in the detection of severe wasting with the new WHO growth standards. AB - OBJECTIVES: The objectives of this study were to estimate the accuracy of using mid-upper-arm circumference (MUAC) measurements to diagnose severe wasting by comparing the new standards from the World Health Organization (WHO) with those from the US National Center for Health Statistics (NCHS) and to analyze the age independence of the MUAC cutoff values for both curves. METHODS: We used cross sectional anthropometric data for 34,937 children between the ages of 6 and 59 months, from 39 nutritional surveys conducted by Doctors Without Borders. Receiver operating characteristic curves were used to examine the accuracy of MUAC diagnoses. MUAC age independence was analyzed with logistic regression models. RESULTS: With the new WHO curve, the performance of MUAC measurements, in terms of sensitivity and specificity, deteriorated. With different cutoff values, however, the WHO standards significantly improved the predictive value of MUAC measurements over the NCHS standards. The sensitivity and specificity of MUAC measurements were the most age independent when the WHO curve, rather than the NCHS curve, was used. CONCLUSIONS: This study confirms the need to change the MUAC cutoff value from <110 mm to <115 mm. This increase of 5 mm produces a large change in sensitivity (from 16% to 25%) with little loss in specificity, improves the probability of diagnosing severe wasting, and reduces false-negative results by 12%. This change is needed to maintain the same diagnostic accuracy as the old curve and to identify the children at greatest risk of death resulting from severe wasting. PMID- 20587677 TI - The detection of simulated retinoblastoma by using red-reflex testing. AB - OBJECTIVE: To determine the ability to detect simulated retinoblastoma by using the red-reflex test. METHODS: Discs that simulated retinoblastoma lesions were affixed to the retina of model eyes with an 8- or 3-mm pupil. The diameter, height, and location of the discs varied. Five examiners evaluated the red reflex with direct ophthalmoscopy by using straight-on and oblique viewing. The generalized estimating equation was used to assess the effects of pupil dilation and observer viewing orientation on tumor detection. RESULTS: Significant 3-way interactions between pupil dilation, observer orientation, and tumor diameter (P < .004) or height (P < .02) were detected; these relationships depended on tumor diameter and height. A similar 3-way interaction was found between pupil dilation, observer orientation, and tumor location in degrees from the fovea (P < .001). Oblique viewing and pupillary dilation improved the tumor-detection rate. With straight-on viewing, the degree of detection was <48% (95% confidence interval [CI]: 39%-57%) for even the largest lesions, compared with 96% (95% CI: 93%-98%) for oblique viewing. For peripheral lesions, the percentage detection for straight-on viewing was 35% (95% CI: 21%-50%) for 30 degrees from the fovea and 16% (95% CI: 2%-31%) for 60 degrees from the fovea; these detection rates significantly improved with oblique viewing to 70% or higher (P < .001). CONCLUSIONS: Detection of simulated retinoblastoma was better when lesions were large and when oblique viewing and dilation were used. Peripheral location was negatively associated with detection. Red-reflex testing to detect leukocoria may be improved with oblique viewing and pharmacologic dilation. PMID- 20587676 TI - Antenatal consent in the SUPPORT trial: challenges, costs, and representative enrollment. AB - OBJECTIVES: The purposes of this study were to quantify the time and effort involved in obtaining prenatal consent for the Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) and to determine whether the enrolled infants were representative of the eligible population. METHODS: Eligible subjects were likely to deliver in the SUPPORT gestational age window (24-27(6/7)] weeks). Data included who approached the subjects for consent, how often they approached, the duration of each contact, whether consent was obtained, and whether subjects were enrolled in the trial. Eligible, nonenrolled infants entered into the Neonatal Research Network Generic Database throughout the period of SUPPORT enrollment were compared with enrolled infants. RESULTS: A total of 2826 women were identified at 18 sites, 2228 were approached for consent, and 1219 (54.7%) agreed. For 76.9% of those approached, <3 visits (mean: 2.0 +/- 1.2 visits) were required to complete the consent process. Of the 659 infants with consent who were delivered within the study window, 611 were enrolled. Mothers who received a neonatal consultation were more likely to give consent (P < .001). The proportion of infants not exposed to steroids was significantly greater in the nonapproached group than in the approached group (20.0% vs 3.4%; P < .0001). CONCLUSION: In a trial that involved preterm infants and required prenatal consent, >5 women were identified as being likely to deliver in the SUPPORT gestational age window for each 1 who delivered an enrolled infant. PMID- 20587678 TI - Maternal smoking and child psychological problems: disentangling causal and noncausal effects. AB - OBJECTIVE: To explore associations of maternal prenatal smoking and child psychological problems and determine the role of causal intrauterine mechanisms. PATIENTS AND METHODS: Maternal smoking and child psychological problems were explored in 2 birth cohorts in Pelotas, Brazil (n = 509, random subsample), and the Avon Longitudinal Study of Parents and Children (ALSPAC) in Britain (n = 6735). Four approaches for exploring causal mechanisms were applied: (1) cross population comparisons between a high-income and a middle-income country; (2) multiple adjustment for socioeconomic and parental psychological factors; (3) maternal-paternal comparisons as a test of putative intrauterine effects; and (4) searching for specific effects on different behavioral subscales. RESULTS: Socioeconomic patterning of maternal prenatal smoking was stronger in the ALSPAC compared with the Pelotas cohort. Despite this difference in a key confounder, consistency in observed associations was found between these cohorts. In both cohorts, unadjusted maternal smoking was associated with greater offspring hyperactivity, conduct/externalizing problems, and peer problems but not with emotional/internalizing problems. After adjusting for confounders and paternal prenatal smoking, only the association with conduct/externalizing problems persisted in both cohorts (conduct problems in the ALSPAC cohort, odds ratio [OR]: 1.24 [95% confidence interval (CI): 1.07-1.46], P = .005; externalizing problems in the Pelotas cohort, OR: 1.82 [95% CI: 1.19-2.78], P = .005; ORs reflect ordinal odds ratios of maternal smokers having offspring with higher scores). Maternal smoking associations were stronger than paternal smoking associations, although statistical evidence that these associations differed was weak in 1 cohort. CONCLUSION: Evidence from 4 approaches suggests a possible intrauterine effect of maternal smoking on offspring conduct/externalizing problems. PMID- 20587679 TI - Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. AB - OBJECTIVE: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. METHODS: Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. RESULTS: MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). CONCLUSIONS: Among 12- to 23 month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines. PMID- 20587680 TI - Pediatrics digital revolution. PMID- 20587681 TI - Tobacco smoke exposure and chronic conditions of childhood. PMID- 20587682 TI - Family-centered rounds on pediatric wards: a PRIS network survey of US and Canadian hospitalists. AB - OBJECTIVE: The goal was to examine pediatric hospitalist rounding practices and characteristics associated with programs conducting family-centered rounds (FCRs). METHODS: The Pediatric Hospitalist Triennial Survey, sent to a subset of pediatric hospitalists on the Pediatric Research in Inpatient Settings listserv from the United States and Canada, consisted of 63 questions on sociodemographic characteristics, training, practice characteristics, and rounding practices. RESULTS: Among 265 respondents (response rate: 70%), 78% practiced in academic hospitals and 22% in nonacademic hospitals. The prevalences of specific rounding categories were as follows: FCRs, 44%; sit-down, 24%; hallway, 21%; others, 11%. FCRs occurred significantly more often in academic (48%) than nonacademic (31%) hospitals (P = .04). FCRs can include pediatric residents, bedside nurses, charge nurses, case managers, pharmacists, and social workers. Academic settings and higher average daily patient censuses, but not FCRs, were significantly associated with prolonged rounding duration. The most commonly perceived FCR benefits included increased family involvement and understanding, trainee role modeling, and effective team communication. Physical constraints, trainees' apprehensions, and time were the main perceived FCR barriers. Greater perceived benefit/barrier ratios, FCR benefits, and family involvement in care were associated with a greater likelihood of conducting FCRs, whereas a greater number of perceived FCR barriers was associated with not conducting FCRs. CONCLUSIONS: FCRs were the most-common rounding category among respondents. FCRs were not associated with a self-reported increase in rounding duration. Successful FCR implementation may require educating staff members and trainees about FCR benefits and addressing FCR barriers. PMID- 20587683 TI - Children's language ability and psychosocial development: a 29-year follow-up study. AB - OBJECTIVES: Little is known on the psychosocial adult outcomes of children's early language skills or intervening circumstances. The aim of this study was to assess the longitudinal trajectory linking childhood receptive language skills to psychosocial outcomes in later life. METHODS: The study comprised 6941 men and women who participated in a nationally representative Birth Cohort Study. Direct assessment of language skills were made at age 5. The sample was studied again at age 34 to assess psychosocial outcomes and levels of adult mental health. Characteristics of the family environment, individual adjustment, and social adaptation in the transition to adulthood were assessed as potential moderating factors linking early language skills to adult mental health. RESULTS: In early childhood, cohort members with poor receptive language experienced more disadvantaged socioeconomic circumstances than cohort members with normal language skills and showed more behavior and psychosocial adjustment problems in the transition to adulthood. At age 34, cohort members with poor early language skills reported lower levels of mental health than cohort members with normal language. After adjustment for family background and experiences of social adaptation, early language skills maintained a significant and independent impact in predicting adult mental health. CONCLUSIONS: Early receptive language skills are significantly associated with adult mental health as well as psychosocial adjustment during early childhood and in later life. The needs of children with language problems are complex and call for early and continuing provision of educational support and services. PMID- 20587685 TI - European insights on diabetic foot pathology. PMID- 20587686 TI - Increased p16CDKN2A protein within feline cutaneous viral plaques, bowenoid in situ carcinomas, and a subset of invasive squamous cell carcinomas. AB - Cutaneous viral plaques and bowenoid in situ carcinomas (BISCs) in cats are thought to be caused by papillomavirus (PV) infection. There is evidence that PVs may also cause some feline invasive squamous cell carcinomas (ISCCs). Human oncogenic PVs degrade retinoblastoma (RB) protein, impairing cell cycle control. Loss of RB function also increases p16(CDKN2A) protein (p16), and increased p16 immunoreactivity within a human oral ISCC indicates that the neoplasm was caused by PV infection. In the present study, p16 immunoreactivity was evaluated in 14 feline viral plaques, 14 BISCs, 7 non-solar-induced ISCCs, 11 solar-induced ISCCs, and 14 trichoblastomas. Increased p16 was present within all viral plaques, BISCs, and non-solar-induced ISCCs. In contrast, little p16 immunoreactivity was visible in the solar-induced ISCCs or trichoblastomas. PV DNA was consistently amplified from viral plaques, BISCs, and non-solar-induced ISCCs. However, just 5 solar-induced ISCCs and 1 trichoblastoma contained PV DNA. Given that both increased p16 immunoreactivity and PV DNA were present within viral plaques, BISCs, and non-solar-induced ISCCs, all 3 may be caused by PV infection. This suggests that feline non-solar-induced ISCCs may develop as a result of neoplastic progression from viral plaques and BISCs. Whether PVs promote this progression is unknown; however, evidence from this study suggests the PV that is associated with viral plaques and BISCs is able to disrupt the p16 RB pathway and therefore could have oncogenic potential. Immunohistochemical detection of p16 appears to be a useful technique to investigate the role of PVs in feline skin disease. PMID- 20587687 TI - Spontaneous malignant mixed Mullerian tumor in a Wistar rat: a case report including immunohistochemistry. AB - This report presents a rare, spontaneous, heterologous, malignant mixed Mullerian tumor observed in a 98-week-old untreated Wistar rat. At necropsy, the right uterine horn was dilated and contained a mass of approximately 10 * 15 mm. Histopathologically the mass consisted of 2 parts with different morphologic characteristics, a polypoid mass protruding into the uterine lumen and a more solid part that replaced the adjacent uterine wall. The solid part exhibited characteristics of a highly infiltrative adenocarcinoma, whereas the composition of the polypoid mass was heterogeneous, consisting of a variety of benign and malignant epithelial and mesenchymal elements. The epithelial components included well-differentiated endometrial and squamous epithelium juxtaposed to carcinosarcomatous areas. The mesenchymal components consisted of well differentiated cartilage and bone along with chondrosarcomatous, rhabdomyomatous, and other mesenchymal elements. Immunohistochemical analysis further supported the diagnosis of malignant mixed Mullerian tumor. PMID- 20587688 TI - Canine gastric carcinoma: immunohistochemical expression of cell cycle proteins (p53, p21, and p16) and heat shock proteins (Hsp27 and Hsp70). AB - Immunohistochemical staining for cell cycle proteins and heat shock proteins was performed on 17 canine gastric carcinomas. The immunoexpression of p53, p21, p16, Hsp27, and Hsp70 was investigated. A study was conducted to determine the histological type and parameters related to tumor malignancy. Possible associations and trends were assessed between the immunoexpression of each protein and tumor type as well as specific parameters of malignancy. High intratumor frequency of cellular p53 immunostaining was observed (61.96% average), but lower frequencies of p21 and p16 expression were present (34.65% and 10.41%, respectively). The p53 overexpression was associated with tumor infiltration (P = .0258). Expression of p21 was lower in undifferentiated carcinomas, and the loss of expression was associated with histopathological parameters characteristic of a poor prognosis such as lymphatic vessel invasion (P = .0258). The lack of p16 immunoreactivity was related to histopathological characteristics of malignancy such as the presence of evident and multiple nucleoli (P = .0475). In contrast, deep tumor infiltration was observed in those carcinomas with a high p16 index (P = .0475). Hsp70 appeared to be overexpressed in all gastric neoplasms included in this study. This is in contrast to Hsp27, because a group of tumors showed complete lack of Hsp27 immunoexpression, whereas the others displayed extensive Hsp27 immunostaining. The differences in Hsp27 did not correlate with any of the histopathological parameters, but Hsp27 immunoexpression was higher in the undifferentiated carcinoma. No significant differences in the expression of the proteins were found in canine gastric carcinomas according to their histological type. These findings may be useful for establishing a prognosis for canine gastric carcinoma. PMID- 20587690 TI - Lymphadenopathy associated with a thyroid carcinoma in a dog. AB - Angiomatoid lesions in a lymph node associated with a thyroid carcinoma of a dog were restricted to the subcapsular and medullary sinuses. Lymphoid atrophy was present, but nodal architecture was not distorted and normal structures were not invaded. Immunohistochemical staining indicated that the vascular spaces formed by spindloid cells were lined by endothelium with a low mitotic index. The spindloid cells were positive for smooth muscle actin, vimentin, and desmin and thus were likely to be fibroblasts, myofibroblasts, smooth muscle cells, and/or pericytes. These features are comparable to vascular transformation of lymph node sinuses in humans (nodal angiomatosis), a nonneoplastic condition often associated with mechanical or functional blockage of efferent lymphatics and veins. PMID- 20587689 TI - Pathbase and the MPATH ontology. Community resources for mouse histopathology. AB - Pathbase, the database of mouse histopathology images, was developed as a resource to provide free access to representative images of lesions in background and mutant strains of laboratory mice. When utilized with diagnostic workups or phenotyping of mutant mice, it can provide a "virtual second opinion" for those working without access to groups of experienced pathologists. This is a community resource, and it facilitates the sharing of expertise and data among members of the pathology community worldwide. MPATH-the mouse pathology ontology-was developed alongside Pathbase for the annotation of images and now represents an important resource for the coding of diagnoses, permitting sophisticated data retrieval and computational analysis of mouse phenotypes. In this article, the structure and use of MPATH is discussed, along with current and future challenges for the coding of mutant mouse phenotypes. PMID- 20587691 TI - The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation. Identification of the nasopharynx as the primary site of infection. AB - To characterize the early events of foot-and-mouth disease virus (FMDV) infection in cattle subsequent to simulated natural exposure, 16 steers were aerosol inoculated with FMDV and euthanized at various times. Samples were collected from each steer antemortem (serum, nasal swabs, and oral swabs) and postmortem (up to 40 tissues per animal) and screened for FMDV by virus isolation and for FMDV RNA by real-time reverse transcription polymerase chain reaction. Tissues that tested positive for FMDV or viral RNA were examined by immunohistochemistry and multichannel immunofluorescence microscopy. In previremic steers, FMDV was most consistently localized to nasopharyngeal tissues, thereby indicating this region as the most important site of primary viral replication. The earliest site of microscopic localization of FMDV antigens was the lymphoid follicle-associated epithelium of the pharyngeal mucosa-associated lymphoid tissue of the nasopharynx at 6 hours postaerosolization. At early time points after aerosol inoculation, viral antigens colocalized with cytokeratin-positive pharyngeal epithelial cells; intraepithelial FMDV-negative, MHCII/CD11c-double-positive dendritic cells were present in close proximity to FMDV-positive cells. Onset of viremia coincided with marked increase of viral loads in pulmonary tissues and with substantial decrease of viral detection in nasopharyngeal tissues. These data indicate that subsequent to aerogenous exposure to FMDV, the temporally defined critical pathogenesis events involve (1) primary replication in epithelial cells of the pharyngeal mucosa-associated lymphoid tissue crypts and (2) subsequent widespread replication in pneumocytes in the lungs, which coincides with (3) the establishment of sustained viremia. PMID- 20587692 TI - Gelatinous marrow transformation and hematopoietic atrophy in a miniature horse stallion. AB - Gelatinous marrow transformation, or serous atrophy of bone marrow fat, has been noted in livestock, laboratory animals, and wildlife in association with an inadequate plane of nutrition, inanition, or intoxication. This is a report of gelatinous marrow transformation and hematopoietic marrow atrophy in a 5-year-old miniature horse stallion. The horse had oral malformations leading to poor food assimilation and emaciation. A bone marrow biopsy obtained to investigate persistent anemia and leukopenia showed hematopoietic atrophy and replacement of fat with a granular extracellular substance, which stained with alcian blue, consistent with acidic mucopolysaccharide content. Surgical correction of the dental abnormalities resulted in improved food assimilation, weight gain, and resolution of cytopenias. In humans, gelatinous bone marrow transformation and hematopoietic atrophy are commonly associated with malnutrition from anorexia nervosa and other causes. The cause of hematopoietic atrophy is unknown but may relate to a nonsupportive marrow microenvironment and inadequate hematopoietic substrate availability. Similar pathogenic mechanisms were suspected in this horse. PMID- 20587693 TI - The haploinsufficient Col3a1 mouse as a model for vascular Ehlers-Danlos syndrome. AB - Vascular Ehlers-Danlos syndrome is a rare genetic disorder resulting from mutations in the alpha-1 chain of type III collagen (COL3A1) and manifesting as tissue fragility with spontaneous rupture of the bowel, gravid uterus, or large or medium arteries. The heterozygous Col3a1 knockout mouse was investigated as a model for this disease. The collagen content in the abdominal aorta of heterozygotes was reduced, and functional testing revealed diminishing wall strength of the aorta in these mice. Colons were grossly and histologically normal, but reduced strength and increased compliance of the wall were found in heterozygotes via pressure testing. Although mice demonstrated no life threatening clinical signs or gross lesions of vascular subtype Ehlers-Danlos syndrome type IV, thorough histological examination of the aorta of heterozygous mice revealed the presence of a spectrum of lesions similar to those observed in human patients. Lesions increased in number and severity with age (0/5 [0%] in 2 month-old males vs 9/9 [100%] in 14-month-old males, P < .05) and were more common in male than female mice (23/26 [88.5%] vs 14/30 [46.7%] in 9- to 21-month old animals, P < .05). Haploinsufficiency for Col3a1 in mice recapitulates features of vascular Ehlers-Danlos syndrome in humans and can be used as an experimental model. PMID- 20587694 TI - Pleuropulmonary blastoma in an equine fetus. AB - Pleuropulmonary blastoma (PPB) is a rare biphasic tumor of children formed by mixed epithelial-and-mesenchymal elements. In this article, the authors report a pulmonary mass in an equine fetus with characteristics of PPB. A soft multicystic broad-based pleural mass was identified in the right caudal lung lobe. The mass comprised solid areas of loose mesenchyme, fenestrated by small ducts or large cystic areas lined by cuboidal epithelium. Mesenchymal elements had moderate anisocytosis, anisokaryosis, and cellular pleomorphism and were immunoreactive for vimentin. Epithelial cells lining ducts and cystic lumina were nonciliated and cuboidal with central round nuclei, minimal cellular pleomorphism, and strong immunoreactivity for cytokeratin. Pertinent characteristics in common with human PPB were the pleural-based location, the dual solid or delicate multiloculated cystic structure, the primitive mesenchymatous stroma fenestrated by well differentiated cuboidal epithelial-lined lumina, and the occurrence during gestation. PMID- 20587695 TI - Comment on comparative device assessments: Humalog KwikPen compared with vial and syringe and FlexPen. PMID- 20587696 TI - Benign violations: making immoral behavior funny. AB - Humor is an important, ubiquitous phenomenon; however, seemingly disparate conditions seem to facilitate humor. We integrate these conditions by suggesting that laughter and amusement result from violations that are simultaneously seen as benign. We investigated three conditions that make a violation benign and thus humorous: (a) the presence of an alternative norm suggesting that the situation is acceptable, (b) weak commitment to the violated norm, and (c) psychological distance from the violation. We tested the benign-violation hypothesis in the domain of moral psychology, where there is a strong documented association between moral violations and negative emotions, particularly disgust. Five experimental studies show that benign moral violations tend to elicit laughter and amusement in addition to disgust. Furthermore, seeing a violation as both wrong and not wrong mediates behavioral displays of humor. Our account is consistent with evolutionary accounts of laughter, explains humor across many domains, and suggests that humor can accompany negative emotion. PMID- 20587697 TI - How do people construct logical form during language comprehension? AB - How do people interpret ambiguous sentences containing more than one quantifier, such as Every kid climbed a tree? We report four sentence-picture matching experiments that used priming to investigate whether comprehenders construct logical-form representations during processing. Experiment 1 investigated priming in active-voice sentences containing transitive verbs and found priming effects of quantifier-scope relations. Experiment 2 demonstrated priming effects when prime sentences were in the passive voice (e.g., A tree was climbed by every kid) and target sentences were in the active voice. Experiment 3 used prime sentences containing existentially quantified agents and universally quantified patients (e.g., A kid climbed every tree) and found no priming effects. Experiment 4 showed no priming effects when prime sentences contained plural nouns but no quantifiers (e.g., Kids like to climb trees), thus calling into question a visual priming account of our priming effects. Our findings suggest that people construct logical-form representations, and they do so after constructing meaning based representations involving quantifiers and thematic-role information. PMID- 20587698 TI - A systematic review of clinical outcomes in patients undergoing meniscectomy. AB - Knee meniscectomy is the most common procedure performed by orthopaedic surgeons. While it is generally believed that loss of meniscal tissue leads to osteoarthritis and poor knee function, many variables may significantly influence this outcome. Through literature search engines including PubMed and Ovid, 4 randomized controlled trials, 2 prospective cohorts, and 23 retrospective cohorts that fit the criteria for level I, II, and III level of evidence were included in this systematic review. For the level III evidence studies, follow-up of 5 years or more was required. Preoperative and intraoperative predictors of poor clinical or radiographic outcomes included total meniscectomy or removal of the peripheral meniscal rim, lateral meniscectomy, degenerative meniscal tears, presence of chondral damage, presence of hand osteoarthritis suggestive of genetic predisposition, and increased body mass index. Variables that were not predictive of outcome or were inconclusive or had mixed results included meniscal tear pattern, age, mechanical alignment, sex of patient, activity level, and meniscal tears associated with anterior cruciate ligament (ACL) reconstruction. While an intact meniscus or meniscal repair was generally favorable in the ACL reconstructed knees, meniscal repair of degenerative meniscal tissue was not favorable. There is a lack of uniformity in the literature on this subject with a preponderance of lower level evidence. Although randomized controlled trials are considered to be the gold standard in medical research, a multicenter prospective cohort design may be more appropriate in assessing the long-term outcome of meniscal surgery and the role that multiple preoperative and intraoperative variables may play in clinical outcomes. In addition, future studies should include factors not assessed or adequately evaluated by several of the included studies, such as meniscal tear pattern, age, mechanical alignment, sex of the patient, activity level, meniscal tears associated with other injuries such as the ACL, smoking, and the effect of previous surgery. PMID- 20587701 TI - A novel sulindac derivative lacking cyclooxygenase-inhibitory activities suppresses carcinogenesis in the transgenic adenocarcinoma of mouse prostate model. AB - Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX) inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G(1) arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis. PMID- 20587702 TI - A novel mechanism of indole-3-carbinol effects on breast carcinogenesis involves induction of Cdc25A degradation. AB - The natural compound indole-3-carbinol (I3C; found in vegetables of the genus Brassica) is a promising cancer prevention or therapy agent. The cell division cycle 25A (Cdc25A) phosphatase is overexpressed in a variety of human cancers and other diseases. In the present study, I3C induced degradation of Cdc25A, arrest of the G(1) cell cycle, and inhibition of the growth of breast cancer cells. We also showed that the Ser124 site of Cdc25A, which is related to cyclin-dependent kinase 2, is required for I3C-induced degradation of Cdc25A in breast cancer cells, and that interruption of the ATM-Chk2 pathway suppressed I3C-induced destruction of Cdc25A. Our in vivo studies of different mutated forms of Cdc25A found that the mutation Cdc25A(S124A) (Ser124 to Ala124), which confers resistance to I3C-induced degradation of Cdc25A, attenuated I3C inhibition of breast tumorigenesis in a mouse xenograft model. The present in vitro and in vivo studies together show that I3C-induced activation of the ATM-Chk2 pathway and degradation of Cdc25A represent a novel molecular mechanism of I3C in arresting the G(1) cell cycle and inhibiting the growth of breast cancer cells. The finding that I3C induces Cdc25A degradation underscores the potential use of this agent for preventing and treating cancers and other human diseases with Cdc25A overexpression. PMID- 20587703 TI - Serum cytokine analysis in a positive chemoprevention trial: selenium, interleukin-2, and an association with squamous preneoplastic disease. AB - This study represents a multiplex cytokine analysis of serum from a 10-month randomized, controlled trial of 238 subjects that investigated the effects of selenomethionine and/or celecoxib in subjects with mild or moderate esophageal squamous dysplasia. The original chemoprevention study found that, among those with mild dysplasia, selenomethionine treatment favorably altered dysplasia grade. The current analysis found that selenomethionine downregulated interleukin (IL)-2 by 9% (P = 0.04), whereas celecoxib downregulated IL-7 by 11% (P = 0.006) and upregulated IL-13 by 17% (P = 0.008). In addition, an increase in IL-7 tertile from baseline to t10 was significantly associated with an increase in dysplasia grade, both overall [odds ratio (OR), 1.47; P = 0.03] and among those with mild dysplasia at t0 (OR, 2.53; P = 0.001). An increase in IL-2 tertile from baseline to t10 was also nonsignificantly associated with worsening dysplasia for all participants (OR, 1.32; P = 0.098) and significantly associated with worsening dysplasia among those with mild dysplasia at baseline (OR, 2.0; P = 0.01). The association of increased IL-2 with worsening dysplasia remained significant in those on selenomethionine treatment who began the trial with mild dysplasia (OR, 2.52; P = 0.03). The current study shows that selenomethionine supplementation decreased serum IL-2 levels, whereas celecoxib treatment decreased IL-7 levels and increased IL-13 levels during a 10-month randomized chemoprevention trial. An increase in IL-2 or IL-7 was associated with increased severity of dysplasia over the course of the trial, especially in those who began the trial with mild dysplasia. The favorable effect of selenomethionine on esophageal dysplasia in the original trial may have been mediated in part by its effect in reducing the levels of IL-2. PMID- 20587704 TI - Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of pre-diabetes. AB - OBJECTIVE: To compare extra-lipid effects of statins and fibrates in relation to the baseline metabolic status of patients. RESEARCH DESIGN AND METHODS: The study involved a group of 242 metabolic syndrome patients with or without pre-diabetes and randomized to atorvastatin, fenofibrate, or placebo. RESULTS: Compared with matched healthy subjects, metabolic syndrome patients exhibited higher plasma levels/activities of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, factor VII, plasminogen activator inhibitor 1, and enhanced monocyte cytokine release. These abnormalities were alleviated by both atorvastatin and fenofibrate treatment. CRP-lowering and monocyte-suppressing actions were more pronounced for atorvastatin in subjects with impaired fasting glucose and for fenofibrate in patients with impaired glucose tolerance. CONCLUSIONS: The presence of pre diabetes potentiates metabolic syndrome-induced abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Both atorvastatin and fenofibrate exhibit multidirectional pleiotropic effects in subjects with metabolic syndrome, the strength of which seem to be partially determined by the type of pre-diabetes. PMID- 20587705 TI - Mining metabolic pathways through gene expression. AB - MOTIVATION: An observed metabolic response is the result of the coordinated activation and interaction between multiple genetic pathways. However, the complex structure of metabolism has meant that a compete understanding of which pathways are required to produce an observed metabolic response is not fully understood. In this article, we propose an approach that can identify the genetic pathways which dictate the response of metabolic network to specific experimental conditions. RESULTS: Our approach is a combination of probabilistic models for pathway ranking, clustering and classification. First, we use a non-parametric pathway extraction method to identify the most highly correlated paths through the metabolic network. We then extract the defining structure within these top ranked pathways using both Markov clustering and classification algorithms. Furthermore, we define detailed node and edge annotations, which enable us to track each pathway, not only with respect to its genetic dependencies, but also allow for an analysis of the interacting reactions, compounds and KEGG sub networks. We show that our approach identifies biologically meaningful pathways within two microarray expression datasets using entire KEGG metabolic networks. AVAILABILITY AND IMPLEMENTATION: An R package containing a full implementation of our proposed method is currently available from http://www.bic.kyoto u.ac.jp/pathway/timhancock. PMID- 20587707 TI - Effect of periodontal treatment on glycemic control of diabetic patients: comment to Teeuw, Gerdes, and Loos. PMID- 20587709 TI - 2009 World Congress on the Insulin Resistance Syndrome: cardiovascular disease concepts. PMID- 20587710 TI - Serum osteocalcin is inversely associated with adipocyte-specific fatty acid binding protein in the Korean metabolic syndrome research initiatives. PMID- 20587711 TI - Correction of serum sodium for glucose concentration in hemodialysis patients with poor glucose control. PMID- 20587712 TI - New pathogenic candidates for diabetic macular edema detected by proteomic analysis. PMID- 20587713 TI - Reduced time points to calculate the composite index. PMID- 20587714 TI - Identification of two new mutations in the glucokinase gene that result in maturity-onset diabetes of the young. PMID- 20587715 TI - Weight reduction may be beneficial for Japanese men with cardiometabolic risk factors even if they are not abdominally obese. PMID- 20587716 TI - Diabetic ketoacidosis and elevated serum lipase in the setting of aripiprazole therapy. PMID- 20587717 TI - International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy: comment to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel. PMID- 20587719 TI - Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes: comment to Kayaniyil et al. PMID- 20587720 TI - Potential additional effect of omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in grade III obese patients undergoing laparoscopic Roux-en-Y gastric bypass: a randomized trial. AB - OBJECTIVE: To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). RESEARCH DESIGN AND METHODS: Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups. RESULTS: Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P < 0.001). Median weight of the omentum was 795 +/- 341 g. In one patient, a duodenal perforation occurred at the time of omentectomy. BMI, blood pressure, glucose, total cholesterol, LDL, and triglycerides significantly improved in both groups at 1, 3, 6, and 12 months of follow-up when compared with basal values. However, there were no consistent statistically significant differences among the groups in terms of metabolic syndrome components, acute phase reactants, and inflammatory mediators. CONCLUSIONS: Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed. PMID- 20587721 TI - Screening adults for pre-diabetes and diabetes may be cost-saving. AB - OBJECTIVE: The economic costs of hyperglycemia are substantial. Early detection would allow management to prevent or delay development of diabetes and diabetes related complications. We investigated the economic justification for screening for pre-diabetes/diabetes. RESEARCH DESIGN AND METHODS: We projected health system and societal costs over 3 years for 1,259 adults, comparing costs associated with five opportunistic screening tests. All subjects had measurements taken of random plasma and capillary glucose (RPG and RCG), A1C, and plasma and capillary glucose 1 h after a 50 g oral glucose challenge test without prior fasting (GCT-pl and GCT-cap), and a subsequent diagnostic 75 g oral glucose tolerance test (OGTT). RESULTS: Assuming 70% specificity screening cutoffs, Medicare costs for testing, retail costs for generic metformin, and costs for false negatives as 10% of reported costs associated with pre-diabetes/diabetes, health system costs over 3 years for the different screening tests would be GCT pl $180,635; GCT-cap $182,980; RPG $182,780; RCG $186,090; and A1C $192,261; all lower than costs for no screening, which would be $205,966. Under varying assumptions, projected health system costs for screening and treatment with metformin or lifestyle modification would be less than costs for no screening as long as disease prevalence is at least 70% of that of our population and false negative costs are at least 10% of disease costs. Societal costs would equal or exceed costs of no screening depending on treatment type. CONCLUSIONS: Screening appears to be cost-saving compared to no screening from a health system perspective, and potentially cost-neutral from a societal perspective. These data suggest that strong consideration should be given to screening-with preventive management-and that use of GCTs may be cost-effective. PMID- 20587722 TI - Diabetes and the severity of pandemic influenza A (H1N1) infection. AB - OBJECTIVE: To confirm the existence of an increased risk of complications from influenza A (H1N1)p among patients with diabetes. RESEARCH DESIGN AND METHODS: Using data from an enhanced influenza surveillance project in Montreal, Canada, and age/sex-specific population estimates of diabetes prevalence, we estimated the risk of hospitalization among persons with diabetes. Comparing hospitalized patients admitted or not to an intensive care unit (ICU), we estimated the risk of ICU admission associated with diabetes, controlling for other patient characteristics. RESULTS: Among 239 hospitalized patients with PCR-confirmed influenza A (H1N1)p, 162 (68%) were interviewed, of whom 22 had diabetes, when 7.1 were expected (prevalence ratio 3.10 [95% CI 2.04-4.71]). The odds ratio for ICU admission was 4.29 (95% CI 1.29-14.3) among hospitalized patients with diabetes compared to those without. CONCLUSIONS: Diabetes triples the risk of hospitalization after influenza A (H1N1)p and quadruples the risk of ICU admission once hospitalized. PMID- 20587723 TI - Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals. AB - OBJECTIVE: Recent large randomized trials have linked adverse cardiovascular and cerebrovascular events with hypoglycemia. However, the integrated physiological and vascular biological mechanisms occurring during hypoglycemia have not been extensively examined. Therefore, the aim of this study was to determine whether 2 h of moderate clamped hypoglycemia could decrease fibrinolytic balance and activate pro-atherothrombotic mechanisms in individuals with type 1 diabetes and healthy individuals. RESEARCH DESIGN AND METHODS: Thirty-five healthy volunteers (19 male and 16 female subjects age 32 +/- 2 years, BMI 26 +/- 2 kg/m(2), A1C 5.1 +/- 0.1%) and twenty-four with type 1 diabetes (12 male and 12 female subjects age 33 +/- 3 years, BMI 24 +/- 2 kg/m(2), A1C 7.7 +/- 0.2%) were studied during either a 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1)) euglycemic or hypoglycemic (2.9 +/- 0.1 mmol/l) clamp or both protocols. Plasma glucose levels were normalized overnight in type 1 diabetic subjects prior to each study. RESULTS: Insulin levels were similar (602 +/- 44 pmol/l) in all four protocols. Glycemia was equivalent in both euglycemic protocols (5.2 +/- 0.1 mmol/l), and the level of hypoglycemia was also equivalent in both type 1 diabetic subjects and healthy control subjects (2.9 +/- 0.1 mmol/l). Using repeated ANOVA, it was determined that plasminogen activator inhibitor (PAI-1), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), E-selectin, P-selectin, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and adiponectin responses were all significantly increased (P < 0.05) during the 2 h of hyperinsulinemic hypoglycemia as compared with euglycemia in healthy control subjects. All measures except PAI-1 were also found to be increased during hypoglycemia compared with euglycemia in type 1 diabetes. CONCLUSIONS: In summary, moderate hypoglycemia acutely increases circulating levels of PAI-1, VEGF, vascular adhesion molecules (VCAM, ICAM, E-selectin), IL-6, and markers of platelet activation (P-selectin) in individuals with type 1 diabetes and healthy individuals. We conclude that acute hypoglycemia can result in complex vascular effects including activation of prothrombotic, proinflammatory, and pro atherogenic mechanisms in individuals with type 1 diabetes and healthy individuals. PMID- 20587724 TI - Painful diabetic neuropathy is associated with greater autonomic dysfunction than painless diabetic neuropathy. AB - OBJECTIVE: Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN. RESEARCH DESIGN AND METHODS: Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed. RESULTS: HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 +/- 1.08 [means +/- SD] vs. 2.67 +/- 1.56), TP (5.73 +/- 1.28 vs. 4.79 +/- 1.51), and SDNN (2.91 +/- 0.65 vs. 1.62 +/- 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT. CONCLUSIONS: This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN. PMID- 20587725 TI - Effects of acute insulin-induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes. AB - OBJECTIVE: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry. RESULTS: In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P or=6.1%. Findings from 7 studies that examined incident diabetes across a broad range of A1C categories showed 1) risk of incident diabetes increased steeply with A1C across the range of 5.0 to 6.5%; 2) the A1C range of 6.0 to 6.5% was associated with a highly increased risk of incident diabetes, 25 to 50% incidence over 5 years; 3) the A1C range of 5.5 to 6.0% was associated with a moderately increased relative risk, 9 to 25% incidence over 5 years; and 4) the A1C range of 5.0 to 5.5% was associated with an increased incidence relative to those with A1C <5%, but the absolute incidence of diabetes was less than 9% over 5 years. Our systematic review demonstrated that A1C values between 5.5 and 6.5% were associated with a substantially increased risk for developing diabetes. PMID- 20587729 TI - Proinflammatory and prothrombotic effects of hypoglycemia. PMID- 20587728 TI - Diabetes and cancer: a consensus report. AB - Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis, 2) risk factors common to both diabetes and cancer, 3) possible biologic links between diabetes and cancer risk, and 4) whether diabetes treatments influence risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed. PMID- 20587730 TI - Neuropathy: the crystal ball for cardiovascular disease? PMID- 20587731 TI - GIP: an inconsequential incretin or not? PMID- 20587732 TI - Is visceral fat responsible for the metabolic abnormalities associated with obesity?: implications of omentectomy. PMID- 20587733 TI - The growing importance of diabetes screening. PMID- 20587734 TI - Do immunosupressive patients really have a severe outcome with H1N1 virus infection? AB - Influenza virus is a common human pathogen that has the potential to cause widespread pandemics. The last pandemic began in April 2009 in CA, USA and killed about 14,000 people since then. The virus affects people at all ages, and school aged children have the highest rates of infection. Chronic lung disease, immunosuppression and pregnancy are risk factors for seasonal influenza and pandemic influenza as well. Here, we report five immunosuppressive patients due to various diseases infected with H1N1 influenza and who were completely revealed after promptly treatment with oseltamivir. PMID- 20587735 TI - A novel kinesin 13 protein regulating rice seed length. AB - The causal gene of a novel small and round seed mutant phenotype (srs3) in rice was identified by map-based cloning and named the SRS3 gene. The SRS3 gene was grouped as a member of the kinesin 13 subfamily. The SRS3 gene codes for a protein of 819 amino acids that contains a kinesin motor domain and a coiled-coil structure. Using scanning electron microscopy, we determined that the cell length of seeds in the longitudinal direction in srs3 is shorter than that in the wild type. The number of cells of seeds in the longitudinal direction in srs3 was not very different from that in the wild type. The result suggests that the small and round seed phenotype of srs3 is due to a reduction in cell length of seeds in the longitudinal direction. The SRS3 protein, which is found in the crude microsomal fraction, is highly expressed in developing organs. PMID- 20587737 TI - The role of visual evoked potentials in the differential diagnosis of functional visual loss and optic neuritis in children. AB - This study aims to determine whether visual evoked potentials can aid the diagnosis of functional visual loss and differentiate it from optic neuritis in children. The medical records and visual evoked potentials of 72 patients registered in the neurophysiological database of our Institution in the period 2000-2009, with diagnoses of functional visual loss or optic neuritis were reviewed retrospectively. In 61 children, visual evoked potentials confirmed the diagnosis: 49 functional visual loss and 12 optic neuritis. Visual evoked potentials were normal in all patients but 1 in the functional visual loss group, while all were abnormal in the optic neuritis group. Overlapping clinical features occurred between the 2 groups as well as prevalent severe visual loss, relative afferent pupillary defect, and papillitis in optic neuritis. Visual evoked potentials are of value in confirming clinical suspicion of functional visual loss, particularly when clinical overlap with optic neuritis occurs. PMID- 20587738 TI - Pivotal Advance: Tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE2 catabolism in myeloid cells. AB - Recent studies suggest that tumor-infiltrated myeloid cells frequently up regulate COX-2 expression and have enhanced PGE2 metabolism. This may affect the maturation and immune function of tumor-infiltrated antigen-presenting cells. In vitro studies demonstrate that tumor-derived factors can skew GM-CSF-driven differentiation of T(h)1-oriented myeloid APCs into M2-oriented Ly6C(+)F4/80(+) MDSCs or Ly6C(-)F4/80(+) arginase-expressing macrophages. These changes enable myeloid cells to produce substantial amounts of IL-10, VEGF, and MIP-2. The tumor mediated inhibition of APC differentiation was associated with the up-regulated expression of PGE2-forming enzymes COX-2, mPGES1 in myeloid cells, and the simultaneous repression of PGE(2)-catabolizing enzyme 15-PGDH. The presence of tumor-derived factors also led to a reduced expression of PGT but promoted the up regulation of MRP4, which works as a PGE2 efflux receptor. Addition of COX-2 inhibitor to the BM cell cultures could prevent the tumor-induced skewing of myeloid cell differentiation, partially restoring cell phenotype and down regulating the arginase expression in the myeloid APCs. Our study suggests that tumors impair the intracellular PGE(2) catabolism in myeloid cells through simultaneous stimulation of PGE(2)-forming enzymes and inhibition of PGE2 degrading systems. This tumor-induced dichotomy drives the development of M2 oriented, arginase-expressing macrophages or the MDSC, which can be seen frequently among tumor-infiltrated myeloid cells. PMID- 20587736 TI - Classification of the gait patterns of boys with Duchenne muscular dystrophy and their relationship to function. AB - Corticosteroids have recently been shown to reduce expected loss of muscle strength in patients with Duchenne muscular dystrophy and extend the time they can walk. We evaluated 43 boys with the condition to determine whether taking corticosteroids is associated with differences in gait pattern, gross motor skills, energy efficiency, and timed motor performance. We used the gait deviation index to quantify the degree of gait pathology and a single measure of gait quality. There were minimal differences in gait pattern, gross motor skills, energy efficiency, or timed motor performance in boys who took corticosteroids compared with those who did not. Clustering by gait deviation index, however, revealed subtle differences between groups in gait patterns, gross motor skills, and energy efficiency. We conclude that, in boys with Duchenne muscular dystrophy, gait pattern deviations are related to function, which can provide further insight into the understanding of disease progression and treatment options to enhance function and maintain ambulation. PMID- 20587739 TI - Technical advance: Caspase-1 activation and IL-1beta release correlate with the degree of lysosome damage, as illustrated by a novel imaging method to quantify phagolysosome damage. AB - In addition to the lysosome's important roles in digestion, antigen processing, and microbial destruction, lysosome damage in macrophages can trigger cell death and release of the inflammatory cytokine IL-1beta. To examine the relationship among endocytosis, lysosome damage, and subsequent events, such as caspase-1 activation and IL-1beta secretion, we developed a method for measuring lysosome disruption inside individual living cells, which quantifies release of Fdx from lysosomes. Unperturbed, cultured BMM exhibited low levels of lysosome damage, which were not increased by stimulation of macropinocytosis. Lysosome damage following phagocytosis differed with different types of ingested particles, with negligible damage after ingestion of sRBC ghosts, intermediate damage by polystyrene (PS) beads, and high levels of damage by ground silica. Pretreatment with LPS decreased the amount of lysosome damage following phagocytosis of PS beads, silica microspheres, or ground silica. Activation of caspase-1 and subsequent release of IL-1beta were proportional to lysosome damage following phagocytosis. The low level of damage following PS bead phagocytosis was insufficient to activate caspase-1 in LPS-activated macrophages. These studies indicate that lysosome damage following phagocytosis is dependent on particle composition and dose and that caspase-1 activation and IL-1beta secretion correlate with the extent of lysosome damage. PMID- 20587740 TI - Comment: Efficacy of metformin and topiramate in prevention and treatment of second-generation antipsychotic-induced weight gain. PMID- 20587741 TI - Treatment of neonatal withdrawal with clonidine after long-term, high-dose maternal use of tramadol. AB - OBJECTIVE: To describe a case of tramadol withdrawal in a neonate and treatment with clonidine after exposure to long-term maternal use of high-dose tramadol. CASE SUMMARY: A 34-week gestational age neonate displayed symptoms of tramadol withdrawal within 48 hours of delivery. Due to a confusing initial clinical picture, including presumed congenital Chlamydia, questionable seizures, and an original report of maternal use of ketorolac (Toradol), diagnosis was delayed until day of life 5. Symptoms included jitteriness, myoclonic movements, and irritability. Upon further questioning of the mother, it was revealed that she was actually taking tramadol 600-800 mg daily. The infant was placed on maintenance therapy with oral clonidine (from 1 to 3 microg/kg orally every 3 hours) until discontinuation on day of life 11. After 3 days off treatment, he began to display symptoms of withdrawal again. Clonidine was restarted at 1 microg/kg orally every 8 hours and he was discharged home on maintenance clonidine therapy at 18 days postnatal age. A 7-day tapering regimen was initiated 2 weeks after discharge, and no further withdrawal symptoms occurred. DISCUSSION: Few published articles are available to guide clinicians on the clinical course and treatment strategies for tramadol dependence and withdrawal. In neonates, the reports are particularly sparse. Traditional agents used in neonatal opioid withdrawal are narcotics (morphine, tincture of opium, methadone), benzodiazepines (diazepam, lorazepam), and phenobarbital. Clonidine use for neonatal abstinence syndrome from narcotics has been shown to be effective alone or in combination with agents such as other opiates and chloral hydrate. Potential benefits of clonidine therapy include shorter duration of therapy, reduced withdrawal symptoms, and decreased length of hospital stay. CONCLUSIONS: Withdrawal can be prolonged in infants exposed to maternal tramadol use. Clonidine may be a safe and effective option for managing symptoms of neonatal tramadol abstinence. PMID- 20587742 TI - L-carnitine for acute valproic acid overdose: a systematic review of published cases. AB - OBJECTIVE: To review the evidence supporting the efficacy and safety of l carnitine in the management of acute valproic acid overdose. DATA SOURCES: MEDLINE (1950-May 2010), EMBASE (1980-May 2010), and Google Scholar (to May 2010) were searched, using the terms carnitine, valproic acid, and carnitine for valproic acid overdose. Reference citations from identified publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: Full-text publications evaluating the use of l-carnitine for management of valproic acid overdose in humans were sought. All studies, regardless of design, case series, and case reports reporting efficacy or safety endpoints were included. All languages were included. Two authors extracted primary data elements including patient demographics, presenting features, clinical management, and outcomes. DATA SYNTHESIS: Seven articles discussing 8 patients and 1 reporting safety data from records of 674 patients were reviewed. Reports covered both pediatric and adult patients with acute exposures to valproic acid mono- and polydrug overdose who were treated with various regimens of l-carnitine. All patients recovered clinically and no adverse effects were noted. CONCLUSIONS: Published evidence of the efficacy and safety of l-carnitine as an antidote for acute valproic acid overdose is limited. Based on the available evidence, it is reasonable to consider l-carnitine for patients with acute overdose of valproic acid who demonstrate decreased level of consciousness. We recommend intravenous administration of 100 mg/kg once, followed by infusions of 50 mg/kg (to a maximum of 3 g per dose) every 8 hours thereafter, continuing until ammonia levels are decreasing (if they were elevated initially) and the patient demonstrates signs of clinical improvement or until adverse events associated with l-carnitine occur. PMID- 20587743 TI - Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients. AB - BACKGROUND: Most literature available for unfractionated heparin (UFH) supports the use of actual body weight for dosing all patients, yet a small proportion of the patients in these studies were morbidly obese. The most appropriate dosing strategy for therapeutic UFH in this patient population is not clearly defined. OBJECTIVE: To better define appropriate UFH dosing strategies in morbidly obese patients and to evaluate the safety of a weight-based heparin nomogram in this patient population. METHODS: Patients with class III (morbid) obesity receiving therapeutic doses of a UFH infusion for greater than 24 hours were evaluated. Two comparator groups of overweight/class I -II obesity and normal/underweight patients were created by matching patients to the class III obesity group. Doses and times to therapeutic activated partial thromboplastin time (aPTT), bleeding rates, and mortality were assessed. RESULTS: The mean infusion rate required to obtain a first therapeutic aPTT was 11.5 units/kg/h in the class III obesity group (n = 94) versus 12.5 units/kg/h and 13.5 units/kg/h for the overweight/class I-II obesity (n = 92) and normal/underweight (n = 87) groups, respectively (p = 0.001). The mean times to a first therapeutic aPTT were 21.3, 22.1, and 29.9 hours, respectively (p = 0.421). There was a statistically significant difference in the infusion rate required to obtain 2 consecutive therapeutic aPTTs between groups (p = 0.016), with higher weight groups requiring smaller (per kilogram actual body weight) infusion rates, but there was no significant difference in the time to reach 2 consecutive therapeutic aPTTs (p = 0.776). There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups. CONCLUSIONS: Morbidly obese patients require smaller UFH infusion rates per kilogram actual body weight compared to patients with lower body mass indices. UFH dosing recommendations should be modified to reflect body mass index classification. PMID- 20587744 TI - Perceptions of practicing pharmacists in Idaho about a potential behind-the counter drug program. AB - BACKGROUND: In late 2007, the Food and Drug Administration (FDA) held public hearings exploring the establishment of a new behind-the-counter (BTC) drug program. However, little is known about the views of pharmacists regarding such a program. OBJECTIVE: To assess the overall perceptions of Idaho's practicing pharmacists about the creation of a formal BTC drug program, the appropriateness of including certain drug categories, specific barriers to its adoption, and the impact of the new program on access to medicines. METHODS: A survey of practicing pharmacists in Idaho was conducted by mail, utilizing anonymous responses. Key questions exploring the views of pharmacists about the new BTC drug program utilized 5-point Likert scales. Data were also collected on respondent characteristics. RESULTS: A total of 357 practicing pharmacists in Idaho (31% response rate) returned the mail survey; 84% of pharmacists agreed that the FDA should be exploring an expanded BTC program, and 88% of pharmacists agreed that this program would improve access to some prescription-only products and convenience for patients. Almost 71% of pharmacists reported a personal willingness to both initiate and monitor certain BTC drug therapies. When focusing on specific drug categories for BTC status, the highest support was for selected agents within smoking cessation therapies (85%), nasal corticosteroids for allergies (81%), and vaccines (75%). Pharmacists who reported low barriers to the adoption of a new BTC program were significantly more likely to support this program than were those reporting high barriers. Only 39% of pharmacists agreed that adequate facilities were currently available for private evaluation and counseling of BTC patients. CONCLUSIONS: Pharmacists in a statewide survey of perceptions regarding a new BTC drug program overwhelmingly believe that patients would benefit. Pharmacists strongly support the development of the new program, and more than two thirds indicate that they would likely participate, given the necessary supporting institutional framework. Perceived barriers are related to willingness to participate and likely can be minimized through education and provision of private consulting areas. PMID- 20587745 TI - Management of hypertension in renal transplant patients: a comprehensive review of nonpharmacologic and pharmacologic treatment strategies. AB - OBJECTIVE: To review the guidelines and literature for the treatment of hypertension in renal transplant patients and to provide guidance to practitioners in the selection of appropriate nonpharmacologic and pharmacologic treatment options. DATA SOURCES: A PubMed search (January 1948-March 2010) was performed using the search terms hypertension, antihypertensive agents, blood pressure, and cardiovascular disease, in combination with renal transplant and kidney transplant. The search was limited to articles published in English. All relevant peer-reviewed original studies, meta-analyses, guidelines, consensus statements, and review articles were examined. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All literature found was evaluated for inclusion. Review articles as well as prospective and retrospective original research articles were reviewed. DATA SYNTHESIS: Hypertension after solid organ transplantation is a problem commonly encountered in patients during their posttransplantation clinic visits. Effective management of these patients' hypertension is crucial, as hypertension left untreated may lead to increased morbidity and mortality as well as graft loss. The unique, multifactorial etiology of hypertension in this population makes treatment choices more challenging compared to treatment of a nontransplant patient. Therefore, to guide practitioners in this process, we developed a hypertension management protocol, taking into account the unique considerations faced in the adult renal transplant population. The review guides practitioners from the initial assessment of patients' hypertension through the evaluation and selection of nonpharmacologic and pharmacologic treatment options and provides information about the discontinuation of certain antihypertensive medications. It also provides a concise, but comprehensive review of the major antihypertensive drug classes and economic considerations. CONCLUSIONS: The management of hypertension in posttransplantation patients is challenging and complicated, yet necessary to prevent morbidity, mortality, and graft loss for these patients. Therapy should be individualized based on patient assessment, response to previous therapy, and economic considerations. PMID- 20587746 TI - Anticholinergic use in children and adolescents after initiation of antipsychotic therapy. AB - BACKGROUND: Second-generation antipsychotics (SGAs) are thought to have a lower likelihood of inducing extrapyramidal symptoms (EPS) than are first-generation antipsychotics (FGAs). Clinical observations suggest that younger patients may be more sensitive to SGA-associated EPS than are adults and require therapy with anticholinergic agents. OBJECTIVE: To determine the proportion of patients 5-18 years of age who received anticholinergic therapy during the initial stages of antipsychotic treatment, as well as to compare anticholinergic utilization across patients receiving aripiprazole, risperidone, and quetiapine, SGAs previously identified as the most commonly prescribed at the academic institution studied. METHODS: Patients 5-18 years of age who were initiating a course of an antipsychotic between January 1, 2005, and September 1, 2008, were identified in a retrospective review of prescription and medical records. Data on demographic characteristics, antipsychotic and anticholinergic utilization, indications, diagnoses, and concomitant medications were collected from the medical record. Only the first therapeutic course of an antipsychotic identified was analyzed. Anticholinergic utilization at antipsychotic initiation and after 30 days was assessed. RESULTS: A total of 235 antipsychotic treatment courses were identified. Of these, 152 patients met our inclusion criteria. Anticholinergic utilization at any time during the first 30 days of treatment was identified in 32 patients (21%), while EPS was documented for 12 patients (8%). FGA or polypharmacy (simultaneous use of >or=2 scheduled antipsychotic) use versus SGA use (OR 18.98; 95% CI 4.74 to 75.95) was the primary characteristic significantly associated with anticholinergic utilization within 30 days after initiation. Of the most commonly used SGAs, risperidone was the drug with which anticholinergics were most frequently prescribed (p = 0.03). CONCLUSIONS: Anticholinergic prescribing exceeded the incidence of EPS, as documented in the medical record (21% vs 8%), and differed across individual medications and antipsychotic class. Utilization of FGAs or polypharmacy was a key predictor of anticholinergic use. PMID- 20587747 TI - A review of oral antiretroviral therapy for the treatment of chronic hepatitis B. AB - OBJECTIVE: To describe the current evidence for the use of oral antiretroviral (ARV) agents in the treatment of chronic hepatitis B (CHB). DATA SOURCES: A search from 1950 to April 2010 was conducted using the databases PubMed and MEDLINE with the search terms chronic hepatitis B, lamivudine, entecavir, adefovir, telbivudine, tenofovir, emtricitabine, clevudine, and pradefovir. The search was limited to trials conducted in humans that were published in the English language. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they evaluated the use of oral ARVs in patients with CHB infection who were not coinfected with hepatitis C, hepatitis D, or HIV. DATA SYNTHESIS: Oral ARVs have revolutionized the treatment of CHB. Studies conducted comparing ARVs have favored entecavir and tenofovir with respect to their ability to decrease hepatitis B virus DNA viral load while minimizing the development of resistance. However, low seroconversion rates, recurrent viremia when ARV therapy is discontinued, and increased resistance rates with longer treatment durations limit the benefit of oral ARVs in the treatment of CHB. Combination therapy has been a suggested solution; however, studies have yet to prove additional benefit over currently recommended monotherapy. CONCLUSIONS: Oral ARVs should continue to be used in the treatment of CHB; however, research is needed to define the optimal duration of therapy, evaluate the utility of combination therapy, and explore novel targets within the hepatitis B life cycle. PMID- 20587749 TI - Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice. AB - Obesity has been shown to create stress in the endoplasmic reticulum (ER), and that initiates the activation of the unfolded protein response (UPR). This has been reported to cause insulin resistance in selective tissues through activation of the inositol-requiring enzyme 1alpha (IRE1alpha)-c-Jun NH(2)-terminal kinase (JNK) pathway, which results in the phosphorylation of the insulin receptor substrate-1 (IRS-1) at an inhibitory site and blocks insulin receptor signaling. In this study, we report that the Src homology domain-containing adaptor protein Nck1, previously shown to modulate the UPR, is of functional importance in obesity-induced ER stress signaling and inhibition of insulin actions. We have examined obese Nck1(-/-) and Nck1(+/+) mice for glucose tolerance, insulin sensitivity, and signaling as well as for ER stress markers and IRS-1 phosphorylation at Ser(307). Our findings show that obese Nck1-deficient mice display improved glucose disposal accompanied by enhanced insulin signaling in liver. This correlates with attenuated IRE1alpha and JNK activation and IRS-1 phosphorylation at Ser(307) compared with obese wild-type mice. Consistent with our in vivo data, we report that downregulation of Nck1 using siRNA in HepG2 cells results in decreased thapsigargin-induced IRE1alpha activation and signaling and IRS-1 phosphorylation at Ser(307), whereas it markedly enhances insulin signaling. Overall, in liver and in cultured cells, we show that depletion of Nck1 attenuates the UPR signal and its inhibitory action on insulin signaling. Taken all together, our findings implicate Nck1 in regulating the UPR, which secondary to obesity impairs glucose homeostasis and insulin actions. PMID- 20587750 TI - Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats. AB - Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore beta-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft beta-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet like structures in 50% of implants, with a mean beta-cell fractional area of 0.8 +/- 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C peptide = 50 +/- 26 pmol/l and insulin = 15 +/- 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID- 20587751 TI - Unsaturated fatty acids prevent desensitization of the human growth hormone secretagogue receptor by blocking its internalization. AB - The composition of the plasma membrane affects the responsiveness of cells to metabolically important hormones such as insulin and vasoactive intestinal peptide. Ghrelin is a metabolically regulated hormone that activates the G protein-coupled receptor GH secretagogue receptor type 1a (GHSR) not only in the pituitary gland but also in peripheral tissues such as the pancreas, stomach, and T cells in the circulation. We have investigated the effects of lipids and altered plasma membrane composition on GHSR activation. Oligounsaturated fatty acids (OFAs) disrupt the structure of membranes and make them more fluid. Prolonged (96 h), but not acute, treatment of the GHSR cells with the 18C OFAs oleic and linoleic acid caused a significant increase in sensitivity of the receptor to ghrelin (EC(50) reduced by a factor of 2.4 and 2.9 at 60 and 120 microM OFAs, respectively). OFAs were found to block the inhibitory effects of ghrelin pretreatment on subsequent ghrelin responsiveness, suggesting that OFAs suppress desensitization of GHSR. Radioligand displacement studies did not show a significant shift in receptor binding after incubation with OFAs. However, it was found that OFA treatment suppressed GHSR internalization, likely explaining OFA induced refractoriness to ligand-induced desensitization. The involvement of lipid rafts in this process was indicated by the altered responsiveness of GHSR under conditions that alter membrane cholesterol. In conclusion, our findings demonstrate the importance of membrane composition for GHSR activation and desensitization and indicate at least part of the mechanism through which OFAs and cholesterol could affect ghrelin's activity in vivo. PMID- 20587752 TI - Note-taking skills of middle school students with and without learning disabilities. AB - For middle school students with learning disabilities (LD), one major component of learning in content area classes, such as science, involves listening to lectures and recording notes. Lecture learning and note-taking are critical skills for students to succeed in these classes. Despite the importance of note taking skills, no research has been reported on the problems that school-age students with LD encounter when recording notes during science lectures. Using a sample size of 90 middle school students, the performance of students with LD was compared to students with no learning disabilities (NLD). Results found that students with LD performed significantly worse than students with NLD in terms of the type and amount of notes recorded and test performance. PMID- 20587753 TI - Disproportionality and learning disabilities: parsing apart race, socioeconomic status, and language. AB - The disproportionate identification of learning disabilities among certain sociodemographic subgroups, typically groups that are already disadvantaged, is perceived as a persistent problem within the education system. The academic and social experiences of students who are misidentified with a learning disability may be severely restricted, whereas students with a learning disability who are never identified are less likely to receive the accommodations and modifications necessary to learn at their maximum potential. The authors use the Education Longitudinal Study of 2002 to describe national patterns in learning disability identification. Results indicate that sociodemographic characteristics are predictive of identification with a learning disability. Although some conventional areas of disproportionality are confirmed (males and language minorities), differences in socioeconomic status entirely account for African American and Hispanic disproportionality. The discrepancy between the results of bivariate and multivariate analyses confirms the importance of employing multivariate multilevel models in the investigation of disproportionality. PMID- 20587754 TI - Do-not-resuscitate orders in suicidal patients: clinical, ethical, and legal dilemmas. AB - BACKGROUND: The authors review the literature related to patients who obtain a Do Not-Resuscitate (DNR) order in preparation for a suicide attempt. OBJECTIVE: The authors review the ethical issues involved in making a decision to resuscitate or not in an attempted suicide with a DNR order. METHOD: The authors address the potential legal consequences of action or inaction and clinical issues to consider before a DNR order is issued. RESULTS: DNR laws do not take into account the situation of the mentally ill person framing a DNR order as a preparation for suicide. CONCLUSION: The article recommends screening for suicidal ideation before issuing DNR orders, having clear hospital policies regarding the honoring of DNR orders if suicide is attempted, and clarification of state DNR laws regarding suicide. PMID- 20587755 TI - Timing of depressive symptom onset and in-hospital complications among acute coronary syndrome inpatients. AB - BACKGROUND: Recent research has reported an association between in-hospital depression and poorer long-term prognosis and a greater risk of in-hospital complications. OBJECTIVE: The purpose of the current study was to examine the relationship between past and incident depressive symptoms and in-hospital complications in acute coronary syndrome (ACS) inpatients. METHOD: A group of 906 ACS inpatients from 12 coronary-care units participated in the study. Incident depressive symptoms were assessed through the Beck Depression Inventory, and participants' were asked about past history of prolonged depressed mood. In hospital complications were noted as present or absent by nurses, and authors conducted logistic-regression analyses. RESULTS: A subset of 492 patients (58.4%) experienced an in-hospital complication, the most common being ischemia (48.8%) and cardiac arrest (7.2%). After adjusting for prognostic indicators, incident and past-combined-with-incident depressive symptoms were significantly associated with an increased risk of experiencing an in-hospital complication. CONCLUSION: Incident symptoms, in particular, seem to be prognostic. This finding suggests that acute emotions may be triggering cardiac complications, and early identification of emotional symptoms is warranted. PMID- 20587757 TI - Healthcare utilization and emotional distress in coronary artery disease patients. AB - BACKGROUND: No studies to-date have examined the various types of emotional distress (ED) for their relative power at predicting costs in patients with coronary artery disease (CAD). OBJECTIVE: The authors investigated the association between expenditure for CAD patients and various measures of emotional/psychological functioning. METHOD: The authors assessed dollars spent in relation to dimensions of the Symptom Checklist 90-Revised and traditional risk factors in the year preceding referral of 164 CAD patients for stress management. RESULTS: Total costs were associated with the Anxiety, Phobic Anxiety, and Psychoticism scales. Hypertension was also associated with increased costs. CONCLUSIONS: Present results indicate an association of higher costs with anxiety. Because the symptoms of anxiety overlap with those of cardiac disease, increased vigilance by both patients and practitioners, resulting in more testing and longer hospital stays is not surprising. Results suggest that there is a potential for substantial cost savings with enhanced detection and treatment of anxiety-spectrum emotional distress. PMID- 20587756 TI - Personality disorders and traits as predictors of incident cardiovascular disease: findings from the 23-year follow-up of the Baltimore ECA study. AB - BACKGROUND: Over the past several decades, the relationship between personality traits and heart disease has interested clinicians and researchers alike. OBJECTIVE: The authors investigated personality disorders (PDs) and PD dimensional traits as prospective risk factors for incident cardiovascular disease (CVD) in the Baltimore Epidemiologic Catchment Area (ECA) follow-up study. METHOD: In 1981, 244 community residents were examined for DSM-III PDs, and PD dimensional traits and were followed for incident CVD by 2004. RESULTS: Logistic-regression models with or without adjustment for potential confounders revealed that Cluster B PD and PD dimensional traits at baseline were consistently associated with increased risk of incident CVD by 2004. Post-hoc analysis also revealed that Cluster B PD and traits also predict CVD mortality. CONCLUSION: Cluster B PDs and dimensional traits may be independent risk factors for incident CVD in the community. PMID- 20587758 TI - Pessimism, worthlessness, anhedonia, and thoughts of death identify DSM-IV major depression in hospitalized, medically ill patients. AB - BACKGROUND: Major depression can be difficult to diagnose in medically ill patients, as distinct mood states may not be adequately differentiated. Previous research has found several dimensions of mood states, including demoralization (hopelessness/helplessness) and anhedonia (inability to experience pleasure). DSM IV major depression was highly prevalent in the clusters of participants typified by high levels of demoralization, and to a slightly lesser extent, anhedonia. OBJECTIVE: The present study provides a further analysis of 312 medically ill patients, examining how key individual symptoms of demoralization and anhedonia relate to DSM-IV major depression. METHOD: The authors used logistic-regression and classification and regression-tree (CART) analysis to relate variables of demoralization/anhedonia and major depression. RESULTS: Two combinations of symptoms 1) pessimism and worthlessness; and 2) pessimism, loss of interest in others, and thoughts of death, were highly associated with major depression. CONCLUSION: The identification of key symptoms, particularly those involving pessimism, may aid clinical understanding and treatment of depression. PMID- 20587759 TI - Decision-making and risk-assessment in living liver donation: how informed is the informed consent of donors? A qualitative study. AB - BACKGROUND: The practice of living donor liver transplantation (LDLT) has been increasing over the past 20 years. In LDLT, a healthy individual offers a substantial part of his or her liver (up to 60%) for the benefit of a terminally ill recipient. OBJECTIVE: The aim of the study was to identify decision-making and risk-assessment patterns of living liver donors and assess whether the principles of informed consent and decision autonomy are being met. METHOD: The authors conducted semistructured clinical interviews with 28 donors before transplantation. RESULTS: The authors found that a decision was being reached before a decision-making process could take place. Surgery risks were perceived and processed in different ways, including the factors of risk-awareness, denial, limited acceptance, and fatalism. DISCUSSION: The authors assess concepts of informed consent and decision autonomy in LDLT, and offer suggestions for donor selection. PMID- 20587760 TI - Impact of delirium on decision-making capacity after hematopoietic stem-cell transplantation. AB - BACKGROUND: Delirium is a common complication of myeloablative hematopoietic stem cell transplantation (HSCT), yet no studies have explored the later effects of an episode of delirium in this setting on patients' decision-making capacity after the acute symptoms of delirium have resolved. OBJECTIVE: The authors assessed the impact of delirium during the acute phase of myeloablative HSCT on later decision making capacity. METHOD: Decision-making capacity was assessed with the MacArthur Competence Assessment Tool in 19 patients before they received their first HSCT and at 30 and 80 days post-transplantation. Delirium was assessed 3 times per week with the Delirium Rating Scale and the Memorial Delirium Assessment Scale from 7 days pre-transplantation through 30 days post-transplantation. RESULTS: Although there was little variance in the pre-treatment scores, with most patients showing very high or perfect scores on decision-making abilities, a multivariate regression model showed that delirium was predictive of a lower reasoning score at Day 30 post-transplantation. CONCLUSION: Patients who experienced a delirium episode during the acute phase of HSCT were not likely to develop clinically meaningful impairments in decision-making capacity post transplantation, although they evidenced minor impairment in their reasoning ability. PMID- 20587761 TI - Health concerns and somatic symptoms explain perceived disability and idiopathic hand and arm pain in an orthopedics surgical practice: a path-analysis model. AB - BACKGROUND: Upper-limb pain disorders are relatively common, and often result in disability, lost time from work, and significant use of healthcare services. OBJECTIVE: The authors adapted and tested a cognitive-behavioral model of health anxiety in 100 patients with hand and arm pain in an orthopedics surgical practice, hypothesizing that increased health concerns would relate to increased perceived disability, and investigating whether patients' pain is related to other increased somatic symptoms. METHOD: Patients with (non-traumatic) hand and arm pain received the Health Anxiety Inventory, the Whitley Index, and the Somatic Symptoms Inventory. Primary analyses were conducted via structural equation modeling. RESULTS: There was a strong, positive, and direct relationship between health concerns and perceived disability. Health concerns were significantly and positively related to somatic symptoms, which, in turn, were significantly positively related to perceived disability and to having idiopathic versus discrete pain. CONCLUSION: The health-anxiety model is relevant to the development of nonspecific, vague, and diffuse (idiopathic) hand and arm pain. PMID- 20587762 TI - Prevalence and determinants of psychiatric disorders in patients with rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic rheumatological disorder among southern Chinese patients in Hong Kong, with an estimated prevalence of 0.33%-0.35%. The resulting chronic pain, disability, social stress, and isolation contribute to the development of psychiatric symptoms. OBJECTIVE: The authors identify the prevalence and determining factors of psychiatric disorders in patients with RA. METHOD: Consecutive RA patients (N=200) were recruited from a rheumatology outpatient clinic. Psychiatric disorders were diagnosed by a psychiatrist using the Chinese-bilingual Structured Clinical Interview for DSM-IV Axis I disorders, Patient Research Version. Sociodemographic and clinical data and subjective health status and perceived social support data were also collected. Factors associated with the occurrence of psychiatric disorders were studied by multivariate analysis. RESULTS: A total of 47 patients were diagnosed with a current psychiatric disorder (depressive disorders, 14.5%; anxiety disorders, 13.0%; schizophrenia, 0.5%). Major depressive disorder and generalized anxiety disorder were the commonest current mood and anxiety disorders, respectively. Independent predictors for a current psychiatric disorder were poverty and perceived poor social support. Limited social interaction, perceived poor social support, high pain intensity, and a family history of psychiatric disorders were independently associated with a current depressive disorder, whereas poverty and perceived poor social support were associated with a current anxiety disorder. CONCLUSION: Depression and anxiety are common in Chinese patients with RA. Patients who lack social support or rely on economic assistance are more prone to the development of psychiatric disorders. PMID- 20587763 TI - Depressive symptoms in pulmonary arterial hypertension: prevalence and association with functional status. AB - BACKGROUND: In patients with left-heart disease, depressive symptoms have a significant impact on functional status and quality of life. The prevalence of depressive symptoms, and their impact on patients with pulmonary arterial hypertension (PAH) is understudied. OBJECTIVE: The authors investigated the prevalence of depressive symptoms in PAH and their correlation with physical functioning. METHOD: Consecutive outpatients with PAH (idiopathic; or associated with scleroderma, congenital heart disease, or anorexiant use) seen in two university PAH clinics were screened. At two outpatient visits, 8 to 16 weeks apart, patients completed the PHQ-8, a well-validated instrument for grading severity of depressive symptoms; they were assessed for cardiac functional class (FC), and performed a 6-minute walk-distance test (6MWD). RESULTS: A group of 100 patients (88% women, 50% with idiopathic PAH) were enrolled. At baseline, 15% of subjects had symptoms suggestive of major depressive disorder; 40% had mild-to moderate depressive symptoms; and 45% had no-to-minimal depressive symptoms. CONCLUSION: Depression is common in patients with PAH, with 55% demonstrating depressive symptoms. These results suggest that screening patients with PAH will identify a large proportion of patients who might benefit from depression therapy. PMID- 20587764 TI - Acute hepatitis and personality change in a 31-year-old man taking prohormone supplement SUS500. AB - BACKGROUND: For decades, anabolic-androgenic steroids have been abused to enhance muscle growth. The harm inflicted by these compounds is well documented. OBJECTIVE: The authors investigated and report on a case in which a male patient self-prescribed some newer dietary supplements, about which less is known. METHOD: The authors report on a case of hepatitis and aggressive personality changes in a 31-year-old man taking purported prohormone agent SUS500 and other, newer supplements. RESULTS: Diagnosis was based on history, mental status exam, and laboratory findings. With discontinuation of all supplements and supportive care, the patient's personality changes resolved, and normal liver function returned. CONCLUSION: The authors conclude that newer anabolic supplements may cause some of the same side effects as traditional steroid hormones. PMID- 20587765 TI - Perimenopausal postpartum depression after conception by assisted reproductive technology. AB - BACKGROUND: Women conceiving after the onset of the menopausal transition may experience hormonal fluctuations that predispose them to postpartum depression. Conception by assisted reproductive technology (ART) may increase this risk. OBJECTIVE: This case report highlights the hormonal and pathophysiological changes that may contribute to the development of postpartum depression during perimenopause. METHOD: The authors report on the case of a perimenopausal woman who developed postpartum depression after conception by ART. RESULTS: The patient responded well to antidepressant treatment, estrogen replacement, and psychotherapy. CONCLUSION: Research into perimenopausal postpartum depression in the setting of ART may lead to improved screening and treatment for at-risk patients. PMID- 20587766 TI - Neuroleptic malignant syndrome: further lessons from a case report. AB - BACKGROUND: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. OBJECTIVE: The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. METHOD: Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. RESULTS: Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. CONCLUSION: This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS. PMID- 20587767 TI - Clozapine-withdrawal catatonia. AB - BACKGROUND: Case reports in which abrupt clozapine discontinuation led to a return of psychosis, autonomic instability, or catatonia have been previously presented in the literature. OBJECTIVE: The authors report on symptom presentation and resolution in a case of abrupt withdrawal of clozapine medication. METHOD: The authors describe the condition and history of the patient, a 49-year-old woman with schizophrenia, the medical support she received, and the re-initiation of her clozapine medication. RESULTS: Symptoms of catatonia and autonomic instability resolved by Day 4 of treatment. CONCLUSION: Patients and their caregivers need to be educated about the effects of abrupt cessation of clozapine administration. PMID- 20587768 TI - Rhabdomyolysis After LSD Ingestion. AB - BACKGROUND: Rhabdomyolysis involves the release of intracellular contents secondary to muscle cell injury; it generally presents with muscle pain and weakness. Illicit drugs, including phencyclidine, MDMA ("ecstasy"), and cocaine, are frequently documented as a cause of rhabdomyolysis. OBJECTIVE: The authors review the literature on LSD-associated rhabdomyolysis. METHOD: The authors provide a new case report of a previously health patient who suffered rhabdomyolysis after LSD ingestion. RESULTS: Although frequently listed as a cause of rhabdomyolysis, there are only limited reports of rhabdomyolysis in patients who have ingested LSD. DISCUSSION: The discussion outlines potential mechanisms and management of LSD-associated rhabdomyolysis. Consultation psychiatrists may be called to assist in management of acute mental-status changes or agitation associated with LSD intoxication in addition to facilitating subsequent chemical-dependency treatment. PMID- 20587769 TI - Novel treatment strategies for depression in patients with hepatitis C. PMID- 20587770 TI - Assessment of decision-making capacity in patients with mental illness. PMID- 20587773 TI - Sho1 and Msb2-related proteins regulate appressorium development in the smut fungus Ustilago maydis. AB - The dimorphic fungus Ustilago maydis switches from budding to hyphal growth on the plant surface. In response to hydrophobicity and hydroxy fatty acids, U. maydis develops infection structures called appressoria. Here, we report that, unlike in Saccharomyces cerevisiae and other fungi where Sho1 (synthetic high osmolarity sensitive) and Msb2 (multicopy suppressor of a budding defect) regulate stress responses and pseudohyphal growth, Sho1 and Msb2-like proteins play a key role during appressorium differentiation in U. maydis. Sho1 was identified through a two-hybrid screen as an interaction partner of the mitogen activated protein (MAP) kinase Kpp6. Epistasis analysis revealed that sho1 and msb2 act upstream of the MAP kinases kpp2 and kpp6. Furthermore, Sho1 was shown to destabilize Kpp6 through direct interaction with the unique N-terminal domain in Kpp6, indicating a role of Sho1 in fine-tuning Kpp6 activity. Morphological differentiation in response to a hydrophobic surface was strongly attenuated in sho1 msb2 mutants, while hydroxy fatty acid-induced differentiation was unaffected. These data suggest that Sho1 and the transmembrane mucin Msb2 are involved in plant surface sensing in U. maydis. PMID- 20587774 TI - Dissecting the functions of class XI myosins in moss and Arabidopsis. PMID- 20587775 TI - Alternatively activated macrophages as cause or effect in airway disease. PMID- 20587772 TI - RNA-seq analysis of sulfur-deprived Chlamydomonas cells reveals aspects of acclimation critical for cell survival. AB - The Chlamydomonas reinhardtii transcriptome was characterized from nutrient replete and sulfur-depleted wild-type and snrk2.1 mutant cells. This mutant is null for the regulatory Ser-Thr kinase SNRK2.1, which is required for acclimation of the alga to sulfur deprivation. The transcriptome analyses used microarray hybridization and RNA-seq technology. Quantitative RT-PCR evaluation of the results obtained by these techniques showed that RNA-seq reports a larger dynamic range of expression levels than do microarray hybridizations. Transcripts responsive to sulfur deprivation included those encoding proteins involved in sulfur acquisition and assimilation, synthesis of sulfur-containing metabolites, Cys degradation, and sulfur recycling. Furthermore, we noted potential modifications of cellular structures during sulfur deprivation, including the cell wall and complexes associated with the photosynthetic apparatus. Moreover, the data suggest that sulfur-deprived cells accumulate proteins with fewer sulfur containing amino acids. Most of the sulfur deprivation responses are controlled by the SNRK2.1 protein kinase. The snrk2.1 mutant exhibits a set of unique responses during both sulfur-replete and sulfur-depleted conditions that are not observed in wild-type cells; the inability of this mutant to acclimate to S deprivation probably leads to elevated levels of singlet oxygen and severe oxidative stress, which ultimately causes cell death. The transcriptome results for wild-type and mutant cells strongly suggest the occurrence of massive changes in cellular physiology and metabolism as cells become depleted for sulfur and reveal aspects of acclimation that are likely critical for cell survival. PMID- 20587776 TI - Mathematical modeling of endocytic actin patch kinetics in fission yeast: disassembly requires release of actin filament fragments. AB - We used the dendritic nucleation hypothesis to formulate a mathematical model of the assembly and disassembly of actin filaments at sites of clathrin-mediated endocytosis in fission yeast. We used the wave of active WASp recruitment at the site of the patch formation to drive assembly reactions after activation of Arp2/3 complex. Capping terminated actin filament elongation. Aging of the filaments by ATP hydrolysis and gamma-phosphate dissociation allowed actin filament severing by cofilin. The model could simulate the assembly and disassembly of actin and other actin patch proteins using measured cytoplasmic concentrations of the proteins. However, to account quantitatively for the numbers of proteins measured over time in the accompanying article (Sirotkin et al., 2010, MBoC 21: 2792-2802), two reactions must be faster in cells than in vitro. Conditions inside the cell allow capping protein to bind to the barbed ends of actin filaments and Arp2/3 complex to bind to the sides of filaments faster than the purified proteins in vitro. Simulations also show that depolymerization from pointed ends cannot account for rapid loss of actin filaments from patches in 10 s. An alternative mechanism consistent with the data is that severing produces short fragments that diffuse away from the patch. PMID- 20587777 TI - The Rsr1/Bud1 GTPase interacts with itself and the Cdc42 GTPase during bud-site selection and polarity establishment in budding yeast. AB - Cell polarization occurs along a single axis that is generally determined in response to spatial cues. In budding yeast, the Rsr1 GTPase and its regulators direct the establishment of cell polarity at the proper cortical location in response to cell type-specific cues. Here we use a combination of in vivo and in vitro approaches to understand how Rsr1 polarization is established. We find that Rsr1 associates with itself in a spatially and temporally controlled manner. The homotypic interaction and localization of Rsr1 to the mother-bud neck and to the subsequent division site are dependent on its GDP-GTP exchange factor Bud5. Analyses of rsr1 mutants suggest that Bud5 recruits Rsr1 to these sites and promotes the homodimer formation. Rsr1 also exhibits heterotypic interaction with the Cdc42 GTPase in vivo. We show that the polybasic region of Rsr1 is necessary for the efficient homotypic and heterotypic interactions, selection of a proper growth site, and polarity establishment. Our findings thus suggest that dimerization of GTPases may be an efficient mechanism to set up cellular asymmetry. PMID- 20587778 TI - Quantitative analysis of the mechanism of endocytic actin patch assembly and disassembly in fission yeast. AB - We used quantitative confocal microscopy to measure the numbers of 16 proteins tagged with fluorescent proteins during assembly and disassembly of endocytic actin patches in fission yeast. The peak numbers of each molecule that accumulate in patches varied <30-50% between individual patches. The pathway begins with accumulation of 30-40 clathrin molecules, sufficient to build a hemisphere at the tip of a plasma membrane invagination. Thereafter precisely timed waves of proteins reach characteristic peak numbers: endocytic adaptor proteins (approximately 120 End4p and approximately 230 Pan1p), activators of Arp2/3 complex (approximately 200 Wsp1p and approximately 340 Myo1p) and approximately 300 Arp2/3 complexes just ahead of a burst of actin assembly into short, capped and highly cross-linked filaments (approximately 7000 actins, approximately 200 capping proteins, and approximately 900 fimbrins). Coronin arrives last as all other components disperse upon patch internalization and movement over approximately 10 s. Patch internalization occurs without recruitment of dynamins. Mathematical modeling, described in the accompanying paper (Berro et al., 2010, MBoC 21: 2803-2813), shows that the dendritic nucleation hypothesis can account for the time course of actin assembly into a branched network of several hundred filaments 100-200 nm long and that patch disassembly requires actin filament fragmentation in addition to depolymerization from the ends. PMID- 20587779 TI - Molecular characterization of EG-VEGF-mediated angiogenesis: differential effects on microvascular and macrovascular endothelial cells. AB - Endocrine gland derived vascular endothelial growth factor (EG-VEGF) also called prokineticin (PK1), has been identified and linked to several biological processes including angiogenesis. EG-VEGF is abundantly expressed in the highest vascularized organ, the human placenta. Here we characterized its angiogenic effect using different experimental procedures. Immunohistochemistry was used to localize EG-VEGF receptors (PROKR1 and PROKR2) in placental and umbilical cord tissue. Primary microvascular placental endothelial cell (HPEC) and umbilical vein-derived macrovascular EC (HUVEC) were used to assess its effects on proliferation, migration, cell survival, pseudovascular organization, spheroid sprouting, permeability and paracellular transport. siRNA and neutralizing antibody strategies were used to differentiate PROKR1- from PROKR2-mediated effects. Our results show that 1) HPEC and HUVEC express both types of receptors 2) EG-VEGF stimulates HPEC's proliferation, migration and survival, but increases only survival in HUVECs. and 3) EG-VEGF was more potent than VEGF in stimulating HPEC sprout formation, pseudovascular organization, and it significantly increases HPEC permeability and paracellular transport. More importantly, we demonstrated that PROKR1 mediates EG-VEGF angiogenic effects, whereas PROKR2 mediates cellular permeability. Altogether, these data characterized angiogenic processes mediated by EG-VEGF, depicted a new angiogenic factor in the placenta, and suggest a novel view of the regulation of angiogenesis in placental pathologies. PMID- 20587780 TI - The HOG pathway dictates the short-term translational response after hyperosmotic shock. AB - Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translational response) is faster than the transcriptional response. Specific functional groups of mRNAs are recruited to ribosomes without any corresponding increase in total mRNA. Among mRNAs under strong translational up-regulation upon shock, transcripts encoding membrane-bound proteins including hexose transporters were enriched. Similarly, numerous mRNAs encoding cytoplasmic ribosomal proteins run counter to the overall trend of down-regulation and are instead translationally mobilized late in the response. Surprisingly, certain transcriptionally induced mRNAs were excluded from ribosomal association after shock. Importantly, we verify, using constructs with intact 5' and 3' untranslated regions, that the observed changes in polysomal mRNA are reflected in protein levels, including cases with only translational up-regulation. Interestingly, the translational regulation of the most highly osmostress regulated mRNAs was more strongly dependent on the stress-activated protein kinases Hog1 and Rck2 than the transcriptional regulation. Our results show the importance of translational control for fine tuning of the adaptive responses. PMID- 20587781 TI - An in vivo model of double-unit cord blood transplantation that correlates with clinical engraftment. AB - Double-unit cord blood transplantation (DCBT) appears to enhance engraftment despite sustained hematopoiesis usually being derived from a single unit. To investigate DCBT biology, in vitro and murine models were established using cells from 39 patient grafts. Mononuclear cells (MNCs) and CD34(+) cells from each unit alone and in DCB combination were assessed for colony-forming cell and cobblestone area-forming cell potential, and multilineage engraftment in NOD/SCID/IL2R-gamma(null) mice. In DCB assays, the contribution of each unit was measured by quantitative short tandem repeat region analysis. There was no correlation between colony-forming cell (n = 10) or cobblestone area-forming cell (n = 9) numbers and clinical engraftment, and both units contributed to DCB cocultures. In MNC transplantations in NOD/SCID/IL2R-gamma(null) mice, each unit engrafted alone, but MNC DCBT demonstrated single-unit dominance that correlated with clinical engraftment in 18 of 21 cases (86%, P < .001). In contrast, unit dominance and clinical correlation were lost with CD34(+) DCBT (n = 11). However, add-back of CD34(-) to CD34(+) cells (n = 20) restored single-unit dominance with the dominant unit correlating not with clinical engraftment but also with the origin of the CD34(-) cells in all experiments. Thus, unit dominance is an in vivo phenomenon probably associated with a graft-versus-graft immune interaction mediated by CD34(-) cells. PMID- 20587782 TI - Drug-dependent clearance of human platelets in the NOD/scid mouse by antibodies from patients with drug-induced immune thrombocytopenia. AB - Drug-induced immune thrombocytopenia (DITP) is a relatively common and sometimes life-threatening condition caused by antibodies that bind avidly to platelets only when drug is present. How drug-dependent antibodies (DDAbs) are induced and how drugs promote their interaction with platelets are poorly understood, and methods for detecting DDAbs are suboptimal. A small animal model of DITP could provide a new tool for addressing these and other questions concerning pathogenesis and diagnosis. We examined whether the nonobese diabetic/severe combined immunodeficient (NOD/scid) mouse, which lacks xenoantibodies and therefore allows infused human platelets to circulate, can be used to study drug dependent clearance of platelets by DDAbs in vivo. In this report, we show that the NOD/scid model is suitable for this purpose and describe studies to optimize its sensitivity for drug-dependent human antibody detection. We further show that the mouse can produce metabolites of acetaminophen and naproxen for which certain drug-dependent antibodies are specific in quantities sufficient to enable these antibodies to cause platelet destruction. The findings indicate that the NOD/scid mouse can provide a unique tool for studying DITP pathogenesis and may be particularly valuable for identifying metabolite-specific antibodies capable of causing immune thrombocytopenia or hemolytic anemia. PMID- 20587784 TI - Histidine-rich glycoprotein promotes bacterial entrapment in clots and decreases mortality in a mouse model of sepsis. AB - Streptococcus pyogenes is a significant bacterial pathogen in humans. In this study, histidine-rich glycoprotein (HRG), an abundant plasma protein, was found to kill S pyogenes. Furthermore, S pyogenes grew more efficiently in HRG deficient plasma, and clots formed in this plasma were significantly less effective at bacterial entrapment and killing. HRG-deficient mice were strikingly more susceptible to S pyogenes infection. These animals failed to control the infection at the local subcutaneous site, and abscess formation and inflammation were diminished compared with control animals. As a result, bacterial dissemination occurred more rapidly in HRG-deficient mice, and they died earlier and with a significantly higher mortality rate than control animals. HRG deficient mice supplemented with purified HRG gave the same phenotype as control animals, demonstrating that the lack of HRG was responsible for the increased susceptibility. The results demonstrate a previously unappreciated role for HRG as a regulator of inflammation and in the defense at the local site of bacterial infection. PMID- 20587783 TI - Highly active antiretroviral treatment against STLV-1 infection combining reverse transcriptase and HDAC inhibitors. AB - Approximately 3% of all human T-lymphotropic virus type 1 (HTLV-1)-infected persons will develop a disabling inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis, against which there is currently no efficient treatment. As correlation exists between the proviral load (PVL) and the clinical status of the carrier, it is thought that diminishing the PVL could prevent later occurrence of the disease. We have conducted a study combining valproate, an inhibitor of histone deacetylases, and azidothymidine, an inhibitor of reverse transcriptase, in a series of baboons naturally infected with simian T-lymphotropic virus type 1 (STLV-1), whose PVL was equivalent to that of HTLV-1 asymptomatic carriers. We show that the combination of drugs caused a strong decrease in the PVL and prevented the transient rise in PVL that is seen after treatment with histone deacetylases alone. We then demonstrate that the PVL decline was associated with an increase in the STLV-1-specific cytotoxic T-cell population. We conclude that combined treatment with valproate to induce viral expression and azidothymidine to prevent viral propagation is a safe and effective means to decrease PVL in vivo. Such treatments may be useful to reduce the risk of HAM/TSP in asymptomatic carriers with a high PVL. PMID- 20587785 TI - Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution. AB - In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and nonrelapse mortality after reduced intensity allogeneic transplantation. However, it also delays immune reconstitution, leading to frequent infections and potential loss of graft-versus-tumor responses. Here, we tested the feasibility of alemtuzumab dose deescalation in the context of fludarabine-melphalan conditioning and human leukocyte antigen (HLA)-identical sibling transplantation. Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were fitted to a linear, 2-compartment model in which dose reduction led to incomplete saturation of CD52 binding sites and greater antibody clearance. Increased elimination was particularly evident in the 20-mg group in patients who had CD52 expressing tumors at time of transplantation. The 20-mg dose was also associated with greater risk of severe GVHD (acute grade III-IV or chronic extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In contrast, dose reduction to 30 mg on day -1 was associated with equivalent clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced intensity conditioning and HLA-identical sibling transplantation. This trial was registered at http://www.ncrn.org.uk as UKCRN study 1415. PMID- 20587786 TI - Nanoparticle-induced vascular blockade in human prostate cancer. AB - The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth. PMID- 20587787 TI - Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN gamma. AB - To explore whether and how T cells can affect myelopoiesis, we investigated myeloid differentiation in a model for T cell-mediated immune activation. We found that CD70-transgenic (CD70TG) mice, which have elevated numbers of interferon-gamma (IFN-gamma)-producing effector T cells in the periphery and bone marrow, are almost devoid of eosinophilic granulocytes. Induction of allergic airway inflammation in these mice failed to induce eosinophilia as well as airway hyperresponsiveness. CD70TG mice also have strongly reduced numbers of eosinophil lineage-committed progenitors, whereas granulocyte/macrophage progenitors from these mice are unable to generate eosinophils in vitro. We found that granulocyte/macrophage progenitors express IFN-gammaR1 and that IFN-gamma is sufficient to inhibit eosinophil differentiation of both murine and human progenitor cells in vitro. We demonstrate that inhibition of eosinophil development in CD70TG mice is IFN-gamma-dependent and that T cell-derived IFN gamma is sufficient to inhibit eosinophil formation in vivo. Finally, we found that IFN-gamma produced on anti-CD40 treatment and during viral infection can also suppress eosinophil formation in wild-type mice. These data demonstrate that IFN-gamma inhibits the differentiation of myeloid progenitors to eosinophils, indicating that the adaptive immune system plays an important role in orchestrating the formation of the appropriate type of myeloid cells during immune activation. PMID- 20587788 TI - Does safe dosing of iodinated contrast prevent contrast-induced acute kidney injury? AB - BACKGROUND: Previous work on contrast-induced acute kidney injury (CI-AKI) has identified contrast volume as a risk factor and suggested that there is a maximum allowable contrast dose (MACD) above which the risk of CI-AKI is markedly increased. We hypothesized that there is a relationship between contrast volume and CI-AKI and that there might be reason to track incremental contrast volumes above and below the MACD limit. METHODS AND RESULTS: Consecutive patients undergoing percutaneous coronary intervention (PCI) were prospectively enrolled from 2000 to 2008 (n=10 065). Patients on dialysis before PCI were excluded (n=155). MACD was defined as (5 mL x body weight [kg])/baseline serum creatinine [mg/dL]) and divided into categories in which 1.0 reflects the MACD limit: < or =MACD ratios (<0.5, 0.5 to 0.75, and 0.75 to 1.0) and >MACD (1.0 to 1.5, 1.5 to 2.0, and >2.0). CI-AKI was defined as a > or =0.3 (mg/dL) or > or =50% increase in serum creatinine from baseline or new dialysis. Multivariable regression was conducted to evaluate the effect of exceeding the MACD on CI-AKI. Twenty percent of patients exceeded the MACD. Risk-adjusted CI-AKI increased by an average of 45% for each category exceeding the MACD (odds ratio, 1.45; 95% confidence interval, 1.29 to 1.62) Adjusted odds ratios for each category exceeding the MACD were 1.60 (95% confidence interval, 1.29 to 1.97), 2.02 (95% confidence interval, 1.45 to 2.81), and 2.94 (95% confidence interval, 1.93 to 4.48). CI-AKI for contrast dose 400 copies/ml) viraemia and the outcomes death, AIDS or immunological response (CD4(+) T-cell count increase > or =50% from 24 weeks) was studied with Poisson regression models, including either time-updated cumulative follow-up, time spent per type of episode or modelling episodes as binary status indicators. RESULTS: During 11,165 person-years of follow-up, 88 patients died, 111 developed AIDS and 2,019 had an immunological response. Longer follow-up time in treatment interruptions increased the risk of AIDS (relative risk [RR] 8.07, 95% confidence interval [CI] 3.98-16.4 per year longer) and impaired immunological response (RR 0.22, 95% CI 0.12-0.41). High-level viraemia was only associated with immunological response (RR 0.55, 95% CI 0.40-0.74), whereas low-level viraemia was not associated with any of the three outcomes. Status indicator models gave similar results. When also including time-updated CD4(+) T-cell counts, the observed associations diminished. CONCLUSIONS: Treatment interruptions and high-level, but not low level, viraemia are strongly associated with clinical outcome, mainly via their effect on CD4(+) T-cell counts. PMID- 20587849 TI - Estimated average annual rate of change of CD4(+) T-cell counts in patients on combination antiretroviral therapy. AB - BACKGROUND: Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4(+) T-cell count according to levels of viraemia in patients on cART. METHODS: A total of 111,371 CD4(+) T-cell counts and viral load measurements in 8,227 patients were analysed. Annual change in CD4(+) T-cell numbers was estimated using mixed models. RESULTS: After adjustment, the estimated average annual change in CD4(+) T-cell count significantly increased when viral load was <500 copies/ml (30.4 cells/mm(3), 95% confidence interval [CI] 26.6-34.3), was stable when viral load was 500-9,999 copies/ml (3.1 cells/mm(3), 95% CI -5.3-11.5) and decreased when viral load was > or =10,000 copies/ml (-14.8 cells/mm(3), 95% CI -4.5--25.1). Patients taking a boosted protease inhibitor (PI) regimen had more positive annual CD4(+) T-cell count changes than patients taking other regimens for any given viral load strata: 30.9 cells/mm(3) (95% CI 27.7-34.1) when viral load was <500 copies/ml, 14.2 cells/mm(3) (95% CI -2.1-30.4) when viral load was 500-9,999 copies/ml and -19.9 cells/mm(3) (95% CI -36.6--3.3) when viral load was >or =10,000 copies/ml. By contrast, among patients taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, the CD4(+) T-cell count significantly decreased when the viral load was 500-9,999 copies/ml (-18.6 cells/mm(3), 95% CI -33.8--3.5) and decreased at a faster rate when the viral load was > or =10,000 copies/ml (-44.4 cells/mm(3), 95% CI -62.0--26.9; P=0.0012, test for interaction). CONCLUSIONS: On average, CD4(+) T-cell counts did not significantly decrease until the viral load exceeded 10,000 copies/ml in patients treated with a boosted PI-containing cART regimen, but decreased in patients taking an NNRTI-based cART regimen when viral load was 500-9,999 copies/ml. PMID- 20587851 TI - Opposite effect of two cytomegalovirus DNA polymerase mutations on replicative capacity and polymerase activity. AB - BACKGROUND: Human cytomegalovirus (HCMV) infections cause significant morbidity in immunocompromised hosts. The aim of this study was to characterize the role of two HCMV DNA polymerase mutations (K805Q and T821I) found in a ganciclovir- and foscarnet-resistant clinical isolate from an AIDS patient. METHODS: The effects of single and dual DNA polymerase mutations on virus susceptibility and replicative capacity, as well as on enzymatic activity, were studied using recombinant viruses generated from overlapping cosmids and DNA polymerase enzymes expressed in rabbit reticulocyte lysates. RESULTS: Recombinant viruses containing mutations K805Q, T821I and K805Q+T821I had 0.8-fold, 5.3-fold and 4.8-fold increases in ganciclovir 50% inhibitory concentration (IC(50)) values and 0.3 fold, 23.3-fold and 15.6-fold increases in foscarnet IC(50) values, respectively, compared with those of the wild-type virus. The recombinant virus T821I had impaired replication in fibroblastic cells on day 2 post-infection with a decrease in viral titres of 3.5-fold, 4.3-fold and 2.6-fold compared to the recombinant wild-type, K805Q and K805Q+T821I viruses, respectively. Enzymatic studies of wild-type and mutant DNA polymerase enzymes in presence of foscarnet resulted in IC(50) values that were similar to those of the recombinant viruses. Steady-state kinetic constants K(m) and V(max) derived from Michaelis-Menten equations showed that the activity of the mutant T821I enzyme was diminished compared with those of wild-type, K805Q and K805Q+T821I mutant enzymes. Thermodynamic stability of the two single mutant enzymes was opposed as shown by computer-assisted three-dimensional modelling studies. CONCLUSIONS: The HCMV DNA polymerase mutation K805Q improved the fitness of the T821I mutation associated with high levels of resistance to foscarnet. PMID- 20587852 TI - Pyrimidine deoxynucleoside and nucleoside reverse transcriptase inhibitor metabolism in the perfused heart and isolated mitochondria. AB - BACKGROUND: The metabolism of pyrimidine deoxynucleosides and nucleoside reverse transcriptase inhibitors has been studied in growing cells. However, many of these drugs are associated with mitochondrial toxicities observed in non replicating tissues, such as in the heart, where their metabolism has not been investigated. METHODS: The aims of this study were twofold. The first was to investigate the metabolism of the thymidine analogues 3'-azido-3'deoxythymidine (AZT) and 2',3'-didehydrodideoxy-thymidine (d4T), and the deoxycytidine (dCyd) analogues 2'-deoxy-3'-thiacytidine (3TC) and 2',3'-dideoxycytidine (ddC) with regard to phosphorylation and breakdown. The second was to investigate their potential effects, singly or in combination with AZT, on metabolism of the naturally occurring deoxynucleosides in the perfused rat heart and in isolated heart mitochondria. RESULTS: The analogue d4T was not metabolized in perfused heart or in isolated mitochondria, and had no effect on either thymidine or dCyd metabolism. The dCyd analogues were both phosphorylated in perfused heart to the triphosphate, but only at the limit of detection and they were not phosphorylated in isolated mitochondria. Neither ddC nor 3TC had any effect on thymidine or dCyd metabolism in either perfused heart or in isolated mitochondria. AZT has been previously shown to inhibit thymidine phosphorylation. When d4T, 3TC or ddC were given with AZT, only ddC caused a significant further decrease in thymidine phosphorylation. CONCLUSIONS: These results indicate that with the exception of the competition between AZT and thymidine, there was little competition for phosphorylation among and between these other nucleoside reverse transcriptase inhibitors and the naturally occurring deoxynucleosides in cardiac tissue and isolated heart mitochondria. PMID- 20587850 TI - Glycated haemoglobin in diabetic women with and without HIV infection: data from the Women's Interagency HIV Study. AB - BACKGROUND: Limited data suggest that glycated haemoglobin (haemoglobin A1c; A1C) values might not reflect glycaemic control accurately in HIV-infected individuals with diabetes. METHODS: We evaluated repeated measures of paired fasting glucose and A1C values in 315 HIV-infected and 109 HIV-uninfected diabetic participants in the Women's Interagency HIV Study. Generalized estimating equations used log A1C as the outcome variable, with adjustment for log fasting glucose concentration in all models. RESULTS: An HIV-infected woman on average had 0.9868 times as much A1C (that is, 1.32% lower; 95% confidence interval 0.9734-0.9904) as an HIV-uninfected woman with the same log fasting glucose concentration. In multivariate analyses, HIV serostatus was not associated, but White, other non Black race, and higher red blood cell mean corpuscular volume (MCV) were statistically associated with lower A1C values. Use of diabetic medication was associated with higher A1C values. In multivariate analyses restricted to HIV infected women, White and other race, higher MCV, and HCV viraemia were associated with lower A1C values, whereas older age, use of diabetic medications and higher CD4(+) T-cell count were associated with higher A1C values. Use of combination antiretroviral therapy, protease inhibitors, zidovudine, stavudine or abacavir was not associated with A1C values. CONCLUSIONS: A1C values were modestly lower in HIV-infected diabetic women relative to HIV-uninfected diabetic women after adjustment for fasting glucose concentration. The difference was abrogated by adjustment for MCV, race and diabetic medication use. Our data suggest that in clinical practice A1C gives a reasonably accurate refection of glycaemic control in HIV-infected diabetic women. PMID- 20587853 TI - Pegylated interferon-alpha2b plus ribavirin therapy in patients with hepatitis C and psychiatric disorders: results of a cohort study. AB - BACKGROUND: Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non psychiatric patients, treated for hepatitis C. METHODS: A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. RESULTS: Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. CONCLUSIONS: Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients. PMID- 20587854 TI - Treatment of chronic hepatitis B in Asia-Pacific countries: is the Asia-Pacific consensus statement being followed? AB - BACKGROUND: The Asia-Pacific consensus guidelines for the management of chronic hepatitis B state that the principal indicators for starting therapy are increased HBV DNA levels (> or =20,000 IU/ml for hepatitis B e antigen [HBeAg] positive status and >2,000 IU/ml for HBeAg-negative status) and alanine aminotransferase (ALT) levels >2x the upper limit of normal. We aimed to determine whether clinicians in the Asia-Pacific region are treating patients with chronic hepatitis B according to the Asia-Pacific consensus statement on the management of chronic hepatitis B. METHODS: An online survey of chronic hepatitis B treatment practices was prepared, consisting of 14 questions grouped into seven categories: patient statistics, treatment statistics, treatment decision, first choice treatment, treatment duration, future directions and patient preference. RESULTS: In total, 124 respondents from 12 countries completed the survey. Most respondents indicated that detectable HBV DNA was either the first or second most important factor when deciding whether to initiate therapy. Many physicians were unsure about initiation of treatment in patients >40 years of age when ALT levels were within the normal range. Oral antiviral drugs were the most frequently used medication because of their effectiveness, safety and ability to provide sustained viral suppression. Conversely, the most important reasons for selecting interferon therapy were effectiveness, fixed duration of treatment and lack of drug resistance. Criteria for stopping treatment generally followed the recommendations included in the guidelines. CONCLUSIONS: These data suggest that clinicians from the Asia-Pacific region use criteria beyond those advocated in treatment guidelines when deciding whether to initiate treatment in HBV-infected patients. PMID- 20587855 TI - Biomarkers of liver injury for hepatitis clinical trials: a meta-analysis of longitudinal studies. AB - BACKGROUND: Liver biopsy and virological end points are standard references for assessing the effect of viral hepatitis treatments. We aimed to review evidence based published data of biomarkers that have been validated as non-invasive alternatives to biopsy as end points for HBV and HCV infection trials. METHODS: Studies were included if there were at least two repeated estimates of fibrosis per patient using biomarkers with at least two studies and a control group. Meta analysis of the percentage of fibrosis progression per year (pFPy) was performed. RESULTS: Two biomarkers were included, FibroTest and liver stiffness measurement (LSM; FibroScan. A total of 1,413 patients with chronic hepatitis C (11 populations) and 772 with chronic hepatitis B (6 populations) were analysed. In a comparison of HCV patients with controls, the FibroTest pFPy was -18% (95% confidence interval [CI] -23--14; P<0.001) in treated patients and the LSM pFPy was -15% (95% CI -28--1; P=0.01), both with differences according to virological responses. In HBV patients, there was a significant decrease of the pFPy only in patients with baseline advanced fibrosis (mean difference -5% [95% CI -10--0.1]; P=0.02). In patients with advanced fibrosis, stratified by virological response, there were similar differences between pFPy estimated either using FibroTest or biopsy, both in HCV and HBV infections. Repeated LSM in HBV patients had an early variability related to necroinflammatory activity. CONCLUSIONS: In patients with chronic hepatitis C and B, the treatment effect on fibrosis progression rate was similarly estimated using FibroTest or biopsy. The same concordance was observed for FibroScan but with a possible overestimation of the fibrosis regression during the first weeks of treatment. PMID- 20587856 TI - Plasma/erythrocyte ribavirin x100 ratio as an indicator of sustained virological response in HCV genotype 1 patients with early virological response. AB - BACKGROUND: On-treatment predictors during antiviral therapy of HCV are useful because they allow discontinuation of an unnecessary treatment in non-responders. Our aim was to evaluate the usefulness of plasma and erythrocyte ribavirin levels in predicting sustained virological response (SVR) in HCV genotype 1 patients undergoing antiviral treatment. METHODS: A total of 40 HCV genotype 1 patients treated with pegylated interferon-alpha2a 180 microg weekly plus ribavirin 1,000 or 1,200 mg daily (according to body weight) were included in the study. Plasma and erythrocyte ribavirin levels were evaluated in all patients at week 12 by HPLC. At week 24, ribavirin levels were reassessed in those achieving early virological response (EVR). RESULTS: A total of 27 patients achieved EVR, whereas 17 achieved SVR. There was no difference among EVR and non-EVR patients in terms of plasma and erythrocyte ribavirin concentrations at week 12. At week 24, EVR patients obtaining SVR exhibited higher mean +/-sd levels of ribavirin in plasma and lower levels in erythrocytes compared with non-SVR patients (in plasma 12.8 +/-10 versus 5.8 +/-4 microM [P<0.02] and in erythrocytes 1,053 +/-504 versus 1,613 +/-589 microM [P<0.03]). When the plasma ribavirin/erythrocyte ribavirin x100 ratio was compared, the difference was enhanced (1.5 +/-1.3 versus 0.4 +/ 0.3 microM; P<0.01). Receiver operating characteristic curve analysis identified a cutoff for plasma ribavirin/erythrocyte ribavirin x100 ratio in predicting SVR of 0.71 with a negative predictive value of 0.8 and a positive predictive value of 0.9, whereas those related to EVR were 1 and 0.6, respectively. CONCLUSIONS: Plasma ribavirin/erythrocyte ribavirin x100 ratio at week 24 seems to be a good indicator of SVR in HCV genotype 1 patients achieving EVR. PMID- 20587857 TI - HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. AB - BACKGROUND: Patterns and pathways of HIV type-1 (HIV-1) antiretroviral (ARV) drug resistance-associated mutations in clinical isolates are conditioned by ARV history and factors such as viral subtype and fitness. Our aim was to analyse the frequency and association of ARV drug resistance mutations in a group of long term vertically infected patients from Argentina. METHODS: Plasma samples from 71 patients (38 children and 33 adolescents) were collected for genotypic HIV-1 ARV resistance testing during the period between February 2006 and October 2008. Statistically significant pairwise associations between ARV resistance mutations in pol, as well as associations between mutations and drug exposure, were identified using Fisher's exact tests with Bonferroni and false discovery rate corrections. Phylogenetic analyses were performed for subtype assignment. RESULTS: In protease (PR), resistance-associated mutations M46I/L, I54M/L/V/A/S and V82A/F/T/S/M/I were associated with each other and with minor mutations at codons 10, 24 and 71. Mutations V82A/F/T/S/M/I were primarily selected by the administration of ritonavir (RTV) in an historical ARV regimen. In reverse transcriptase, thymidine analogue mutation (TAM)1 profile was more common than TAM2. The non-nucleoside K103N+L100I mutations were observed at high frequency (15.5%) and were significantly associated with the nucleoside mutation L74V in BF recombinants. CONCLUSIONS: Associations of mutations at PR sites reflect the frequent use of RTV at an early time in this group of patients and convergent resistance mechanisms driven by the high exposure to protease inhibitors, as well as local HIV-1 diversity. The results provide clinical evidence of a molecular interaction between K103N+L100I and L74V mutations at the reverse transcriptase gene in vivo, limiting the future use of second-generation non-nucleoside reverse transcriptase inhibitors such as etravirine. PMID- 20587860 TI - Use of newer antiretroviral agents, darunavir and etravirine with or without raltegravir, in pregnancy: a report of two cases. AB - BACKGROUND: Although antiretroviral therapy during pregnancy is associated with significant reductions in the risk of vertical transmission of HIV, attainment of this outcome in highly treatment-experienced pregnant women might be complicated by the lack of active drugs available to assemble a potent regimen. The recent licensing and availability of darunavir, etravirine and raltegravir has broadened management options available for highly treatment-experienced patients. However, data on their safety and efficacy in preventing vertical transmission are limited. METHODS: A retrospective chart review of two cases describing obstetrical, infant and treatment outcomes associated with the use of regimens that include darunavir and etravirine with or without raltegravir during pregnancy was conducted. RESULTS: We document two cases of pregnant HIV-positive women treated with antiretroviral therapy including darunavir, etravirine and raltegravir. Vertical transmission was averted and no congenital anomalies were observed. CONCLUSIONS: In the absence of human development toxicity data for these agents, these cases provide preliminary anecdotal data on their safety during pregnancy. Although the outcomes of these cases are reassuring, additional studies and registries are required to establish the safety and efficacy of these agents during pregnancy. PMID- 20587859 TI - Combination therapy of vaccinia virus infection with human anti-H3 and anti-B5 monoclonal antibodies in a small animal model. AB - BACKGROUND: Treatment of rare severe side effects of vaccinia virus (VACV) immunization in humans is currently very challenging. VACV possesses two immunologically distinct virion forms in vivo - intracellular mature virion (MV, IMV) and extracellular virion (EV, EEV). METHODS: Antibody-mediated therapeutic efficacy was determined against VACV infection in a small animal model of progressive vaccinia. The model consisted of severe combined immunodeficiency mice infected with VACV New York City Board of Health vaccine strain and treated with monoclonal antibodies (mAbs). RESULTS: Here, we show that combination therapy with two fully human mAbs against an immunodominant MV antigen, H3 (H3L), and an EV antigen, B5 (B5R), provides significantly better protection against disease and death than either single human monoclonal or human vaccinia immune globulin, the currently licensed therapeutic for side effects of smallpox vaccination. CONCLUSIONS: The preclinical studies validate that this combination of mAbs against H3 and B5 is a promising approach as a poxvirus infection treatment for use in humans. PMID- 20587861 TI - Parvovirus-B19-associated fulminant myocarditis successfully treated with immunosuppressive and antiviral therapy. AB - Fulminant myocarditis is a rare inflammatory heart disease affecting relatively young adults. We describe a case of a 27-year-old male with acute onset severe heart failure. A rapid and accurate diagnostic approach suggested parvovirus B19 as the most probable cause for this fulminant viral myocarditis. Initial haemodynamic support, intensive immunosuppressive and antiviral therapy resulted in a complete recovery within 2 weeks. This case demonstrates the importance of a detailed diagnosis, allowing better classification of the underlying pathology and subsequent targeted treatment. PMID- 20587858 TI - Anthropometry in the prediction of sleep disordered breathing in HIV-positive and HIV-negative men. AB - BACKGROUND: Body mass index (BMI), waist circumference (WC) and neck circumference (NC) are important screening tools for sleep disordered breathing (SDB); however, the utility of anthropometry for this purpose has not been evaluated among HIV-positive patients. METHODS: HIV-negative men (n=60), HIV positive men receiving highly active antiretroviral therapy (HIV-positive/HAART; n=58) and HIV-positive men not receiving HAART (HIV-positive/no HAART; n=41) from the Multicenter AIDS Cohort Study underwent a nocturnal sleep study and anthropomorphic assessment. Moderate-severe SDB was defined as an apnea/hypopnea event rate > or =15 episodes/h. Receiver operating characteristic (ROC) curves were used to compare the ability of different anthropometric measurements to predict SDB within each group. RESULTS: Moderate-severe SDB was found in 48% of men (HIV-negative [57%], HIV-positive/HAART [41%] and HIV-positive/no HAART [44%]). The performance of BMI, WC and NC to predict SDB was excellent among the HIV-negative men (ROC areas under the curve [AUCs] 0.83, 0.88 and 0.88, respectively) and fair among the HIV-positive/HAART group (AUC 0.71, 0.77 and 0.77, respectively). By contrast, these measurements had no predictive value in the HIV-positive/no HAART group (AUC 0.43, 0.41 and 0.45, respectively). Moreover, in the HIV-positive/no HAART group, moderate-severe SDB was independently associated with serum C-reactive protein > or =3.0 mg/l (odds ratio 6.9; P=0.04) and HIV RNA>10,000 copies/ml (odds ratio 7.1; P=0.05). CONCLUSIONS: BMI, WC and NC had a better predictive value for moderate-severe SDB in HIV positive men compared with HIV-positive [corrected] men, and had no value among HIV-positive/no HAART men. Among this latter group, systemic inflammation might contribute to the pathogenesis of SDB. PMID- 20587862 TI - Renal action of C-type natriuretic peptide: advocating the isolated perfused rat kidney model. AB - C-type natriuretic Peptide (CNP), the third natriuretic peptide (NP) identified, is mainly expressed in the nervous system and endothelial cells. In addition, CNP is believed to be produced locally in tubular cells and glomeruli of normal human kidneys. CNP exerts mainly vasodilatory and antimitogenetic effects rather than regulation of body fluid homeostasis via autocrine or paracrine pathway. Many factors, such as shear, pro-inflammatory cytokines and lipopolysaccharide, can regulate the production and excretion of CNP both in vivo and in vitro. However, little information about the renal action of CNP was obtained in the past from the model of isolated perfused rat kidney in which variables could be changed in a controlled manner and systemic influences could be eliminated. However, reviewing the data from the studies that used this model inspires us to conclude that such model can be a useful tool to probe the undiscovered aspects of the renal actions of CNP and should be advocated for future studies on it. PMID- 20587863 TI - Impact of immunosuppression and chemotherapy on reactivation of viral hepatitis. AB - Chemotherapy drugs, biological medications that are used to treat cancer, may cause hepatic side effects. Patients with pre-existing viral hepatitis may be more susceptible to exacerbation of their underlying liver disease, and risk of drug-induced hepatotoxicity. We conducted a search on immunosuppression, and its impact on reactivation of viral hepatitis, using the electro-nic medical databases. Before starting chemotherapy, it is recommended to record the past history of liver disease and check for hepatitis B virus (HBV) and hepatitis C virus (HCV) serology. In immunosuppressed patients, radiation toxicity, graft versus host disease, hepatic veno-occlusive disease, acalculous cholecystitis, tumor infiltration, ischemia, other viruses such as CMV and her-pes virus, and systemic infection should also be considered. Transplant recipients with serologic evidence of previous infection with hepatitis B or C, or those who receive organs from a seropositive donor, should have viral load levels monitored before and after transplantation and, may also require treatment. We believe that there is a role for prophylactic use of antiviral treatment in patients at risk for HBV reactivation. PMID- 20587864 TI - Prevalence of silent gastrointestinal complications in maintenance renal transplant population. AB - This study aims to determine the prevalence of silent GI complications within a stable renal transplant population and to investigate whether the conversion to enteric-coated myco-phenolate sodium (EC-MPS, Myfortic) would improve symptom scores. This was a single-center, open-label, non-randomized, prospective study. Patients without any history of GI com-plaints were evaluated by means of the gastrointestinal symptom rating scale (GSRS), with subse-quent switch to EC-MPS in a group of patients. Silent complications were defined as patients who voiced no GI complaints at clinic visits despite a score of > or = 2 on GSRS scale. A total of 236 stable patients participated in the trial. The prevalence of baseline scores > or = 2 was relatively high with abdominal pain 29.66%, reflux 37.28%, indigestion 50%, constipation 58.47% and diarrhea 33.4%. Of 236 patients, 80 were converted to EC-MPS. There was statistically significant improvement on all scales in the subgroup of patients with GSRS score > or = 2 (P < 0.05). In conclusion, the GSRS scale identified a high percentage of silent gastrointestinal complications in this renal transplant population. The converted patients with higher GSRS scores reported a sustained improvement. PMID- 20587865 TI - Effect of an educational program on awareness about peritoneal dialysis among patients on hemodialysis. AB - Several years after the initial usage of continuous ambulatory peritoneal dialysis (CAPD), the percentage of patients using this continues to be very low constituting about 15% of all patients with end-stage renal disease (ESRD). In this study, we attempt to define the impact of an educational program for improving the use of CAPD. This is a quasi-experimental study (before-after) conducted with educational materials including workshop, teaching by booklet and showing educational films, performed in Urmia, Iran. We designed a questionnaire for data collection and enrolled 160 patients with an aim-based sampling method. We used descriptive statistics and Friedman test for analysis in SPSS software version 11.5. The overall patients' information about CAPD defined by total scoring was as follows: 75% had little information; 19% had moderate information and 6% of patients were well informed. All the information levels increased after intervention. Our study suggests that the poor utilization of CAPD is due to relative un-awareness about PD and/or lack of adequate facilities. PMID- 20587866 TI - Serum zinc concentrations in patients on maintenance hemodialysis and its relationship with anemia, parathyroid hormone concentrations and pruritus severity. AB - Zinc (Zn) deficiency has been reported in 40-78% of hemodialysis (HD) patients and may be associated with anemia and pruritus and probably limiting the expression of renal osteodystrophy. This study was designed to explore possible correlation between serum zinc concentration and anemia, intact parathyroid hormone (iPTH) concentration and pruritus severity in HD patients. During a case control study, the serum Zn concentration of patients on maintenance HD was compared with those of the healthy controls and with the cut-off point of 70 mcg/dL as the risk of Zn deficiency. The mean serum Zn concentration in patients on maintenance HD was significantly lower than that of the control group; however, it was not different with the cut-off point of 70 microg/dL. No correlation between serum Zn concentration and hematologic indices was detected. A significant positive correlation between serum Zn concentration and erythropoietn dose was noted. No correlation was found between serum Zn concentration and PTH level or pruritus severity. In conclusion, the results of this study showed that zinc concentrations were lower in HD patients compared to controls, however, the effects of routine supplementation of zinc to control anemia, serum PTH level or pruritus severity are yet doubtful. PMID- 20587867 TI - Pregnancy during hemodialysis: a single center experience. AB - Successful pregnancy outcome is an uncommon occurrence in women requiring chronic dialysis treatment. We reviewed the course and outcome of 9 pregnancies occurred in women on chronic hemodialysis in our center from 1999-2007; 5 of them ended with delivery of alive newborns, 2 with fetal deaths in-utero, and 2 with abortions. The average age of patients was 34 years. The etiology of the original kidney disease was unknown in 44.4% of the cases, and only 22.2% of the patients maintained diuresis. Dialysis started in 8 cases before the diagnosis of pregnancy. The average gestational age at diagnosis was 14 weeks. We modified the prescription of dialysis in 4 patients by increasing the frequency of the dialysis sessions to 6 per week and in 3 by increasing the duration of each session to 6 hours. Anemia was present in all the cases; 3 patients received erythropoietin and 4 patients required transfusion. The pregnancy was com plicated in 44% of the cases by a polyhydramnios. The average time at delivery was 33 weeks and it was achieved in 80% of pregnancies through vaginal route. The average weight of newborns was to 2380 g. We conclude that pregnancy in women on hemodialysis is possible. The success of pregnancy may be influenced by the residual diuresis and early diagnosis to improve the quality of dialysis by increasing the dialysis dose. PMID- 20587868 TI - Patterns of anti-hypertensive therapy in diabetic patients with and without reduced renal function. AB - Renal function deterioration is a common complication in patients with diabetes mellitus and hypertension. Appropriate use of anti-hypertensive agents and tight control of blood pressure (BP) can minimize and delay such complications. This study was performed in order to investigate the utilization patterns of anti hypertensive agents and to evaluate BP control among diabetic-hypertensive patients with and without reduced renal function. In a retrospective cohort study, all diabetic-hypertensive patients attending The Al-Watani Medical Governmental Center from August 01, 2006 until August 01, 2007 were enrolled in the study. Patients with congestive heart failure and/or end-stage renal disease were excluded from the study. The proportion of use of five different anti hypertensive drug classes were compared for all patients receiving 1, 2, 3, or 4 drugs, and separately among patients with and without reduced renal function. Over 60% of patients were receiving angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocker (ARB), followed by diuretics (40.8%), calcium channel blockers (25.1%) and (beta-blockers (12.5%). The majority of patients (> 55%) were either on mono or no drug therapy. Patients on monotherapy were mostly receiving ACEI/ARB (60%). In patients with reduced renal function, use of diuretics, but not ACEI/ARB or CCB, was higher and 41.8% of the patients were on monotherapy compared to 46.6% in patients with normal renal function. The proportion of patients achieving good BP control was 20% with mono-therapy and 28% with combination therapy. Our study suggests that the pattern of anti hypertensive therapy was generally consistent with inter-national guidelines. Areas of improvement include increasing use of ACEI/ARB and diuretics, decreasing the number of untreated patients, and increasing the proportion of patients with well controlled BP in this population. PMID- 20587869 TI - Factors affecting urinary calculi treatment by extracorporeal shock wave lithotripsy. AB - Extracorporeal Shock Wave Lithotripsy (ESWL) is still the treatment of choice for most renal and upper ureteric stones; however the outcome depends on multiple factors. The objective of this study was to investigate the effects of stone density, as measured by Hounsfield Units (H.U) by non-contrast Computerized Tomography (CT), stone size and stone location on ESWL treatment outcome of urinary calculi in Jordanian patients. 65 patients underwent clinical, biochemical and radiological assessments followed by ESWL treatment. Statistical analyses including chi-square, analysis of variance (ANOVA), correlation, regression were performed for statistical significance between ESWL treatment, stone fragmentation and stone density, size and location in the renal pelvis. ESWL success rate was high (94%) for low density stones (< 500 Hounsfield units). In general CT densities of 750 Hounsfield units or less were almost always successfully treated by ESWL. An inverse association between ESWL treatment outcome and stone size was also documented. CT stone density and stone size combined account for nearly 73% of the variation in the number of shock waves required to attain fragmentation. Stones located in lower calyceal area had less success rates. In conclusion, stones with higher density, large size and lower location may better be managed by percutaneous nephrolithotomy. PMID- 20587870 TI - Anatomy of the collecting system of lower pole of the kidney in patients with a single renal stone: a comparative study with individuals with normal kidneys. AB - At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and variations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors). Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces) was carried out using intravenous pyelogram (IVP) in 100 cases with urinary stone (study cases) and 400 persons with normal kidneys (control subjects). The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whitney and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA) in control subjects and in patients was 112.5 +/- 10.7 and 96.6 +/- 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= < 0.001). The mean infundibulum-uretero-pelvic angle (IUPA) in control subjects and study cases was 53.5 +/- 12.7 and 42.6 +/- 13.4, respectively. There was significant correlation between decreased angle and stone formation (P = or < 0.001). The mean length of infundibulum of lower pole of kidney (IPIL) in controls and study patients was 22.5 +/- 4.1 and 27.5 +/- 7.7, respectively, which was statistically significant (P< 0.001). The mean number of calyces in lower pole of the kidney (LPCN) in controls and study patients was 2.6 +/- 0.6 and 3 +/- 0.9, respectively, which was statistically significant (P = or < 0.002). There was no significant correlation between distribution of calyces and stone formation (P= 0.366). Our study suggests that abnormal renal anatomy was more common in patients with lower pole kidney stone and should be considered a risk factor for forming lower pole kidney stone. PMID- 20587871 TI - Hypercalciuria in children with urinary tract symptoms. AB - We performed this prospective study to determine the urinary calcium to creatinine ratio (Ca/Cr) in children with different urinary symptoms. We studied 523 children in our nephrology clinic with an age range of 3 to 14 years (mean= 8) and male to female ratio of 0.61. All the children had at least one of the urinary tract symptoms (dysuria, frequency, urgency, abdominal and/or flank pain, diurnal incontinence or enuresis), microscopic hematuria, urinary tract infection or urolithiasis. Fasting urine was collected for measuring calcium and creatinine and the results were compared to the values for the normal Iranian children. Ca/Cr ratio of more than 0.2 (mg/mg) was considered as hypercalciuria. Of all the patients, 166 (31.3%) were hypercalciuric. Urine Ca/Cr ratio was significantly higher in all the subgroups with one or more of the urinary symptoms (P< 0.001). We conclude that urine Ca/Cr ratio is significantly increased in children with all types of urinary symptoms. We recommend measuring urinary calcium in all children with urinary tract symptoms, especially if unexplained. PMID- 20587872 TI - Meeting the American Diabetic Association standards of diabetic care. AB - Although there are numerous studies on diabetes mellitus in Saudi Arabia, data on the extent to which American Diabetic Association (ADA) standards of diabetic care are met, is scarce. We studied the computerized records of adult diabetic patients followed-up in outpatient internal medicine clinics at our tertiary care center in Riyadh, Saudi Arabia to find out how many of them met the ADA standards of diabetic care regarding fasting blood glucose, HbA1c, LDL-C, hypertension, proteinuria screening and use of anti-platelet, lipid lowering or recommended anti-hypertensive medications. Out of 1,188 type-2 diabetic patients studied, blood pressure readings were available in 1180 (99%) while results of fasting blood glucose, HbA1c, LDL-C and albuminuria screening were available for 1123 (95%), 968 (81%), 1037 (87%) and 307 patients, (26%) respectively. Patients achieving the ADA targets for overall, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, LDL-C and albuminuria screening were 39.0%, 40.6%, 74.6%, 25.0%, 21.8%, 55.5% and 34.9%, respectively. For prevention of cardiovascular events, 61.0%, were using angiotensin converting enzyme inhibitors (ACE-I) or angiotensin-2 receptor blockers (ARBs) or both, while 71.5% and 72.3% of our patients were on anti-platelet and statin medications, respectively. In conclusion, as reported in most other studies, we also found that ADA standards of diabetic care are not met in most of our diabetic patients, indicating that these standards are easy to preach than to practice. There is need for further research to investigate the reasons for this failure and to adopt better multi disciplinary approach and realistic targets in the future. PMID- 20587873 TI - 24-hour creatinine clearance reliability for estimation of glomerular filtration rate in different stages of chronic kidney disease. AB - Glomerular Filtration Rate (GFR) is considered the best overall index of renal function currently used. Measurement of 24 hours urine/plasma creatinine ratio (UV/P) is usually used for estimation of GFR. However little is known about its accuracy in different stages of Chronic Kidney Disease (CKD) aim: is to evaluate performance of UV/P in classification of CKD by comparing it with isotopic GFR (iGFR). 136 patients with CKD were enrolled in this study 80 (59%) were males, 48 (35%) were diabetics. Mean age 46 +/- 13. Creatinine Clearance (Cr.Cl) estimated by UV/P and Cockroft-Gault (CG) was done for all patients, iGFR was the reference value. Accuracy of UV/P was 10%, 31%, 49% within +/- 10%, +/- 30%, +/- 50% error respectively, r(2) = 0.44. CG gave a better performance even when we restrict our analysis to diabetics only, the accuracy of CG was 19%, 47%, 72% in +/- 10%, +/- 30% and +/- 50% errors respectively, r(2) = 0.63. Both equations gave poor classification of CKD. In conclusion, UV/P has poor accuracy in estimation of GFR, The accuracy worsened as kidney disease becomes more severe. We conclude 24 hours CrCl. is not good substitute for measurement of GFR in patients with CKD. PMID- 20587874 TI - Impact of cytotoxin-associated gene A of Helicobacter pylori strains on microalbuminuria in type 2 diabetes. AB - Cytotoxin-associated gene A (CagA) positive strains of H. pylori have a significant correlation with gastritis and peptic ulcer, and may induce persistent systemic inflammatory response, increase vascular damage, and compromise glycemic control in diabetic patients. To evaluate correlation between infection by cagA positive strains of H. pylori and occurrence of microalbuminuria and glycemic control in type 2 diabetic patients, we prospectively studied 98 dyspeptic type 2 diabetic patients as a study group and 102 dyspeptic non-diabetic subjects as a control group. Gastric biopsy specimens obtained with endoscopy were cultured to isolate H. pylori. All the isolated H. pylori strains from cultures were used for detection of cagA gene by polymerase chain reaction. There was no significant difference between study and control groups regarding infection with cagA positive strains of H. pylori ( P= 0.145). Furthermore, there was no significant differences between both groups concerning the incidence of microalbuminuria ( P= 0.145). On the other hand, there was an extremely statistically significant difference in the incidence of microalbuminuria and glycemic control in the diabetic patients between those infected with cagA positive strains of H. pylori and cag A negative starins (P= 0.000). We conclude that infection with cagA positive strains of H. pylori are strongly associated with the increased incidence of microalbuminuria and poor glycemic control in type 2 diabetic patients. PMID- 20587875 TI - Beta-2 microglobulin levels in hemodialysis patients. AB - The objective of the study was to determine the level of beta2-microglobulin (beta2-m) in hemodialysis (HD) patients and the factors affecting it. This cross sectional, hospital based study was conducted between September and December 2008 at the Hemodialysis unit of Shalamar Hospital, Lahore. All patients with end stage renal disease (ESRD) who were on maintenance HD for more than three months were included in the study. Patients with acute renal failure and on dialysis for less than three months were excluded. Demographic data were collected and details of dialysis (type of dialyzers, dialysate bath, membrane used) were recorded. Blood samples of the patients were drawn for hematological (hemoglobin, hematocrit), biochemical (urea, creatinine, uric acid, albumin) and beta2-m level measurement. The total number of patients studied was 50. The major causes of ESRD included diabetes mellitus and hypertension seen in 37 (74%) and 10 patients (20%), respectively. The beta2-m levels were significantly elevated in the study patients; 92.6 +/- 17.1 mg/L with a range of 54 to 130 mg/L as compared to 2.0 +/ 1.29 mg/L in the control group. The patients' age had a statistically significant relationship with the beta2-m level. The major reason for increased beta2-m level was use of low-flux dialyzers. Synthetic polysulphone membrane, bicarbonate, ultra pure dialysate and duration on HD were not asso-ciated with high beta2-m levels. Also, we found an inverse relationship between beta2-m levels and serum albumin of the study patients. Our study suggests that the beta2 m levels are significantly high in dialysis patients. Use of low-flux dialyzer seems to be the major reason for the high beta2-m levels. Age and albumin have statistically significant relationship with beta2-m levels. PMID- 20587876 TI - Relation of serum albumin and C-reactive protein to hypotensive episodes during hemodialysis sessions. AB - To evaluate the effect of albumin serum levels and C-reactive protein (CRP) on the course of dialysis induced hypotension (DIH) in chronic hemodialysis (HD) patients, we studied 58 chronic hemodialysis patients in our center during 2007. We investigated the correlation between serum albumin, highly sensitive CRP (hs CRP) and DIH. The mean of the serum albumin levels was 4.2 +/- 0.5 g/dL, and 32.8% of the patients revealed hypoalbuminemia. Occurrence of DIH among HD patients was 27.6%. The mean of serum albumin levels in the DIH group was significantly lower compared with the normotensive group (3.9 +/- 0.4 vs 4.3 +/- 0.5 g/dL, respectively, P= 0.008). The mean of the hs-CRP levels was significantly higher in the DIH group compared with the normotensive group (12.9 +/- 12 vs. 7.2 +/- 5.2 mg/dL, respectively, P= 0.01). We conclude that high level of CRP and hypoalbuminemia may be predictors of DIH. PMID- 20587877 TI - Spontaneous rupture of the spleen: a rare complication in a patient with lupus nephritis on hemodialysis. AB - Rupture of the spleen is a life threatening condition. We report a 40-year-old fe male patient, a known case of lupus nephritis receiving hemodialysis, who developed spontaneous rupture of the spleen during the course of her illness. The patient was managed conservatively with gradual regression of hematoma without further complications. PMID- 20587879 TI - Amyloidosis secondary to xanthogranulomatous pyelonephritis: a rare association. AB - Xanthogranulomatous pyelonephritis and secondary systemic amyloidosis are relatively common pathologies with innumerable cases being reported now and then. However the association of these entities is an extremely uncommon occurrence with only ten cases described in the literature. Clinical remission of amyloidosis develops in a majority of these patients after removal of the renal lesion. We present a case of this rare association in a young female who under went nephrectomy for a non-functioning kidney. A histopathological diagnosis of xanthogranulomatous pyelonephritis was made. In addition there were deposits of amyloid in the glomeruli and the interstitial blood vessels. PMID- 20587878 TI - H1N1 in dialysis units: prevention and management. AB - Dialysis patients are at increased risk of contracting influenza A H1N1 and developing serious illness. Increasing the awareness of dialysis patients and continuous education and training of medical staff on early recognition and management of influenza A H1N1 can help in saving the life of patients. Antiviral drugs and influenza vaccines are effective in providing adequate immunity in dialysis patients with strict implementation of infection control policies and procedures can help in preventing and controlling the dissemination of influenza A H1N1 in dia-lysis units. We report a case of a patient who presented with H1N1 influenza and developed acute kidney injury during his hospitalization and his course with disease. PMID- 20587880 TI - Renal lymphangiectasia associated with chronic myeloid leukemia. AB - Renal lymphangiectasia is a rare disorder characterized by dilatation of peripelvic, renal and perirenal lymphatic ducts. The exact etiology is not known. Congenital forms and ac-quired forms have been described. The latter has been attributed to obstruction of draining retro-peritoneal lymphatic ducts caused by either infection, inflammation or any other cause. We des-cribe the rare association of renal lymphangiectasia with chronic myeloid leukemia, which is probably not yet reported in the medical literature. PMID- 20587881 TI - Intrarenal epidermoid cyst presented as an enlarged multicystic kidney. AB - This report describes a case of large multiple and multilocular epidermoid cysts affecting the left kidney of a 67 old male. The condition was accidentally discovered during the ultrasonography for left loin pain and revealed enlarged left kidney with picture suggestive of hydronephrosis. Grossly, the kidney was distorted cysts that were filled with a cheesy material. The histologic picture of an end stage kidney disease was apparent in the compressed renal parenchyma by these cysts that were identical to an epidermoid cyst elsewhere. In conclusion, although rare, epidermoid cyst of the kidney could cause serious kidney damage leading to an end stage kidney disease. Epidermoid cyst of the kidney could be multiple producing a picture similar to hydronephrosis and broadening the differential diagnosis of multicystic disease of the kidney. PMID- 20587882 TI - Salmonella typhi sepsis and rhabdomyolysis with acute renal failure: a rare presentation of a common disease. AB - Typhoid is associated with a number of complications and is commonly seen in India. Rhabdomyolysis is rarely reported. We report herewith a patient with Salmonella typhi sepsis who presented with rhabdomyolysis and acute renal failure. PMID- 20587883 TI - Senior-Loken syndrome in an Iranian family. AB - Senior-Loken syndrome is a rare entity that combines familial juvenile nephronophthisis with retinal dystrophy. Herein, we report Senior-Loken syndrome in six members of an Iranian family with progressive blindness and renal failure since childhood. Although, this syndrome was reported from other parts of the world, report of six members of one family with this syndrome is rare. To the best of our knowledge, this is the first report from Iran. PMID- 20587884 TI - Membranoproliferative glomerulonephritis secondary to chronic myeloid leukemia. AB - The nephrotic syndrome (NS) is a well documented complication of hematological malignancies. However, chronic myeloid leukemia (CML) is rarely complicated by the NS, and it occurs usually after allogenic stem cell transplantation or interferon alpha therapy for CML. The NS as a complication of untreated CML is also rare. We report a 31-year-old patient who presented with features of The NS. He was diagnosed to have CML one year ago and was on irregular treatment with imatinib mesylate. The renal biopsy and immunofluorescence revealed membrano proliferative glomerulonephritis type I. The patient was retreated with imatinib mesylate and the NS resolved gradually over three months. This maybe the third case in literature of membrano-proliferative glomerulonephritis associated with CML. PMID- 20587885 TI - Parathyroid gland tuberculosis associated with secondary hyperparathyroidism in hemodialysis patient. PMID- 20587886 TI - Response to iron sucrose in dialysis patients sensitive to iron dextran. PMID- 20587887 TI - Release technique: maturing arteriovenous fistula early. PMID- 20587888 TI - Dialysis fluid regeneration by forward osmosis: a feasible option for ambulatory dialysis systems. PMID- 20587889 TI - Kidney diseases prevention and organ donation: need for strategies. PMID- 20587890 TI - Familial distal renal tubular acidosis presenting as acute quadriparesis. PMID- 20587891 TI - Marfan syndrome and focal segmental glomerulosclerosis: a novel association. PMID- 20587892 TI - Characteristics of intradialytic hypotension: experience of Agadir Center Morocco. AB - We report in this retrospective study the experience of our hemodialysis (HD) center in the incidence of intradialytic hypotension (IDH) over 18 months. We first studied the demographic, clinical, biological and morphological data of our 52 HD patients and compared the characteristics of patients with frequent IDH and those without. We found that factors significantly associated with IDH include diabetes, left ventricular hypertrophy, impaired diastolic function, weight gain and high ultrafiltration rates. Despite these results, further larger studies are required to confirm them. PMID- 20587893 TI - Pediatric urolithiasis in the central coast of Tunisia: Epidemiologic changes over the past twenty-five years. AB - The incidence of pediatric urolithiasis has been constantly decreasing during the past twenty-four years (1982-2007) in Tunisia as well as in other Mediterranean countries. This study was undertaken to observe the incidence of stone disease and its composition in children. Our study shows a downward trend of incidence of urolithiasis in pediatric patients over the last 25 years. The prevalence of calcium oxalate stones has constantly increased with decrease in the stones related to infections Whewellite (calcium oxalate) was more frequent in children of school age. In conclusion, the decrease in struvite frequency in children patients during the past twenty-five years and the stabilization of calcium phosphate stones are the result of a significant improvement of diagnostics and the treatment of urinary tract infections in the young children in our country. PMID- 20587894 TI - Brown tumors in patients with chronic renal failure and secondary hyperparathyroidism: report of 12 cases. AB - Brown tumors are unusual but serious complications of renal osteodystrophy. We retrospectively studied 12 patients presenting with chronic renal failure and brown tumor related to secondary hyperparathyroidism. Eleven patients were on chronic hemodialysis. The median duration between renal failure and end stage renal failure was 36 months (range: 12-190 months) and the median duration in dialysis for 11 cases: 92 months (range: 72-252 months). The bone pain was noted in all cases (100%), pathological fracture in one case (8%) and a palpable bone tumor in 10 cases (83%). Elevated serum calcium (> 2.35 mmol/L) was noted in four cases (33%), elevated serum Phosphate (> 1.78 mmol/L) in ten cases (80%), elevated serum alkaline phosphate (> 290 UI/L) in all cases and intact PTH was > 300 pg/mL in all cases with a serum median rate at 1475 pg/mL (range: 682-3687 pg/L). Subtotal parathyroidectomy was performed in all cases with a resultant decrease in size of brown tumors. We report here patient with CKD with unusual frequency and variable locations. This may be attributed to the lack of the new calcium free phosphate binders and calcimimetics. PMID- 20587895 TI - Pattern of glomerular diseases in Sudanese children: a clinico-pathological study. AB - Glomerular diseases are a common cause of chronic kidney disease (CKD) in many countries. The pattern of glomerular diseases has been reported in adult Sudanese patients but there has been no previous study on Sudanese children. The aim of this study is to describe the pattern of glomerular diseases in Sudanese children from a clinico-pathological perspective. We retrospectively reviewed the clinical records of 321 children seen with nephritis/nephrosis at the Pediatric Nephrology Unit, Soba University Hospital and Dr. Salma Dialysis and Kidney Transplantation Centre, Khartoum, Sudan during the period from 2002 to 2007. Biopsies were studied with light microscopy and immuno-histochemistry with electron microscopy performed abroad in selected patients (predominantly Alport's). The mean age of the 321 study children was 8.71 years (range 2 months-16 yrs) of whom, 188 were males (60.2%). The most common presentation was with the nephrotic syndrome, seen in 202 patients (62.9%). The most common glomerular disease encountered was minimal change disease, seen in 96 children (29.9%), followed by post-infectious GN in 78 (24.3%) and focal and segmental glomerulosclerosis, seen in 44 patients (13.7%). Membranoproliferative GN (MPGN) was seen in 43 patients (13.4%) while mesangioproliferative GN was seen in 24 (7.5%). Systemic lupus erythematosus (SLE) was the most common secondary glomerular disease accounting for 16 patients (4.9%). HBsAg was positive in 10 patients and the most common associated lesion was MPGN (60%). Histopathology enabled us to change the therapy in 55.3% of the patients. Our study suggests that the pattern of GN in our cohort of patients is comparable with reports from other parts of the world with a high prevalence of post-infectious GN. Renal biopsies have an important part in planning therapy and management. Also, the importance of establishing a Sudanese renal registry including pediatric patients is stressed. PMID- 20587896 TI - The history of nephrology in Tunisia. PMID- 20587897 TI - Clinical importance of quality of life measures in head and neck cancer. PMID- 20587898 TI - Surgical voice restoration after total laryngectomy: an overview. AB - Total laryngectomy is potentially a debilitative surgery resulting in compromise of some of the most basic functions of life including speech and swallowing. This may have a profound adverse effect on the patient's physical, functional, and emotional health, and may result in a decreased quality of life (QOL). Until the 1980s, total laryngectomy was regarded as a dreadful, but often, life-saving procedure for which there was little alternative, and was used as a last resort. At that time survival at any cost in terms of QOL was paramount and many laryngectomies were forced into an isolated life as a mute and dysphasic recluse. Most attempts at voice restoration produced inconsistent results and often techniques were laborious, expensive, and ineffective, particularly when carried out as a salvage procedure after failed radiotherapy. Progress in voice rehabilitation, following total laryngectomy, over the last 30 years, has made an enormous difference in the whole concept of the management of laryngeal cancers. Currently there are several options available for these patients, namely, esophageal speech, artificial larynx, and tracheoesophageal speech. The choice of speech rehabilitation varies from patient to patient, but tracheoesophageal voice has become the preferred method. This article provides a brief account of surgical voice restoration after total laryngectomy. Special emphasis has been given to the surgical technique, special considerations, complications, and the prevention / treatment of tracheoesophageal voice restoration. PMID- 20587899 TI - Novel therapeutic approaches to squamous cell carcinoma of the head and neck using biologically targeted agents. AB - Despite significant improvements in the treatment and outcomes of patients with squamous cell carcinoma of the head and neck (SCCHN) that have resulted from technological advances in radiation delivery and the use of cytotoxic chemotherapy, there is still a pressing need for novel therapies. In the last two decades, our understanding of the molecular biological basis of cancer has provided us with a new framework for developing specific targeted therapies. It is likely that the next wave of developments will include active small molecule inhibitors of epidermal growth factor receptor (EGFR) (and other members of the c erbB family of receptors), antiangiogenic agents, and drugs that can increase proapoptotic signaling in cancer cells. As with cetuximab, it is most likely that these new agents will first find a niche in the context of combination regimens with standard anticancer therapeutics. PMID- 20587900 TI - Challenges in integrating 18FDG PET-CT into radiotherapy planning of head and neck cancer. AB - Radiotherapy forms one of the major treatment modalities for head and neck cancers (HNC), and precision radiotherapy techniques, such as intensity-modulated radiotherapy require accurate target delineation to ensure success of the treatment. Conventionally used imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging are used to delineate the tumor. Imaging, such as positron emission tomography (PET)-CT, which combines the functional and anatomic modalities, is increasingly being used in the management of HNC. Currently, 18-fluorodeoxyglucose is the most commonly used radioisotope, which is accumulated in areas of high glucose uptake, such as the tumor tissue. Because most disease recurrences are within the high-dose radiotherapy volume, defining a biological target volume for radiotherapy boost is an attractive approach to improve the results. There are many challenges in employing the PET CT for radiotherapy planning, such as patient positioning, target edge definition, and use of new PET tracers, which represent various functional properties, such as hypoxia, protein synthesis, and proliferation. The role of PET-CT for radiotherapy planning is ever expanding and more clinical data underlining the advantages and challenges in this approach are emerging. In this article, we review the current clinical evidence for the application of functional imaging to radiotherapy planning and discuss some of the current challenges and possible solutions that have been suggested to date. PMID- 20587901 TI - The role of intensity-modulated radiotherapy in head and neck cancer. AB - Intensity-modulated radiotherapy (IMRT) has been a significant technological advance in the field of radiotherapy in recent years. IMRT allows sparing of normal tissue while delivering radical radiation doses to the target volumes. The role of IMRT for parotid salivary gland sparing in head and neck cancer is well established. The utility of IMRT for pharyngeal constrictor muscle and cochlear sparing requires investigation in clinical trials. The current evidence supporting the use of IMRT in various head and neck subsites has been summarized. Sparing of organs at risk allows for dose-escalation to the target volumes, taking advantage of the steep dose-response relationship for squamous cell carcinomas to improve treatment outcomes in advanced head and neck cancers. However, dose-escalation could result in increased radiation toxicity (acute and late), which has to be studied in detail. The future of IMRT in head and neck cancers lies in exploring the use of biological imaging for dose-escalation using targeted dose painting. PMID- 20587902 TI - The current role of tissue engineering in head and neck reconstruction. AB - Tissue engineering is an emerging field that has the potential to revolutionize the field of reconstructive surgery by providing off-the-shelf replacement products. The literature has become replete with tissue engineering studies, and the aim of this article is to review the contemporary application of tissue engineered products. The use of tissue-engineered cartilage, bone and nerve in head and neck reconstruction is discussed. PMID- 20587903 TI - Benign vs malignant soft tissue neoplasms: limitations of magnetic resonance imaging. AB - AIMS: Various features have been described in the literature to differentiate benign from malignant lesions. The aim of the present study was to study the accuracy of each of these features and that of magnetic resonance imaging (MRI) in diagnosing malignant lesions. MATERIALS AND METHODS: Fifty-five consecutive patients presenting with neoplastic (both benign and malignant) lesions diagnosed clinically and on ultrasound were studied and their MRI features were compared with the findings on surgical exploration and histopathologic examination. RESULTS: There were 32 (58%) benign and 23 (42%) malignant masses. Malignant masses were more common in patients older than 20 years (83%), and these had symptoms of less than 6 months duration (75%), as against benign lesions. The swelling was painful in 8 malignant masses and these were more common in the upper limbs (61%). Various features of malignant lesions were size more than 5 cm in 83%, change in signal intensity from homogenous on T1-weighted images to heterogenous on T2-weighted images in 74%, irregular margins in 74%, and heterogenous contrast enhancement in 91%. The accuracy of these features was 76%, 58%, 78%, and 60%, respectively. Most benign and malignant lesions were intramuscular in location. A significant number (38%) of benign lesions were located in the intermuscular facial plane. Definitive diagnosis was made in 42% of the lesions. CONCLUSIONS: MRI is an excellent modality for evaluating soft tissue neoplasms; however, prediction of a specific diagnosis and differentiation of malignant and benign lesions is not always possible. PMID- 20587904 TI - Renal tumors presentation: changing trends over two decades. AB - PURPOSE: We have analyzed the changing trends in surgical treatment of renal tumors over the last 2 decades with regard to age incidence, presentation, incidental detection, and histopathology. MATERIALS AND METHODS: Records of renal tumors were analyzed from January 1, 1988 to December 31, 2007. Data were split into 4 parts based on a 5-year time period, 1 for each cohort of patients: cohort 1 (1988-1992)-103 patients, cohort 2 (1993-1997)-161 patients, cohort 3 (1998 2002)-243 patients, and cohort 4 (2003-2007)-304 patients. A comparative study was performed with regard to age incidence, presentation, incidentallomas, histopathology, and management with statistical analysis. RESULTS: Out of 811 renal tumors, 17.63% cases were benign and 82.37% were malignant. In the first cohort, 34.95% cases were detected in the seventh decade as compared with cohort 4 in which these were detected in the sixth (34.86%) and fifth decades (21.38%). Incidentallomas increased from 11 (10.67%) in cohort 1 to 84 (27.63%) in cohort 4 (P = 0.001). The cases of surgically treated tumors increased in number from 103 to 304 in cohort 4. Among the presenting features, incidence of weight loss, flank pain, and lump decreased while other clinical syndromes were constant. Only open radical nephrectomy was performed in the first 2 consecutive timeperiods. Laparoscopic radical nephrectomy was increasingly used in cohort 4 as compared with cohort 3 (121 vs 32, respectively). Similarly, open nephron sparing surgery (NSS) was increasingly used in cohort 4 as compared with cohort 3. Among the histopathologies, clear cell carcinoma was most common (73.35 %), but Fuhrman grading showed a trend toward more cases detected with grade 1 and 2 in cohort 4; 23.73% and 61.86%, respectively, as compared with 15.85% and 45.12% in cohort 1 (P = 0.001); more T1 tumors were detected (63.42% in cohort 4 as compared with 41.46% in cohort 1). CONCLUSIONS: A majority of renal tumors presented as symptomatic tumors. Recently, tumors are being detected at an early stage and grade; in the younger patients, with an increasing trend of laparoscopic and open NSS. PMID- 20587905 TI - Prepubertal testicular tumors: our 10 years experience. AB - BACKGROUND: Testicular tumors in the pediatric population are distinct from those of the adults. In contrast to the prevalence data reported in tumor registries, several studies have shown that a majority of the prepubertal testis tumors are benign. We retrospectively analyzed a series of prepubertal testicular tumors. MATERIALS AND METHODS: A retrospective review of all testicular tumors at our institution was done from Jan 1999 to Dec 2008. Data relating to presentation, evaluation, and management were collected. RESULTS: A total of 22 children with prepubertal testicular tumors were identified. The mean age at presentation was 4.6 years. Mature teratoma, epidermoid cysts, immature teratoma, and yolk sac tumor accounted for 49.94%, 13.62%, 9.08%, and 18.16%, respectively. All surgeries were successful with respect to cancer control and testicular preservation. CONCLUSIONS: Benign tumors formed the majority (72.64%) of the tumors that were encountered, with yolk sac tumors (18.16%) being a minority. Testicular preserving surgery appears to be a feasible option for benign tumors and is safe and efficacious in long-term follow-up. PMID- 20587906 TI - Psychosocial disorders in women undergoing postoperative radiation and chemotherapy for breast cancer in India. AB - BACKGROUND: Breast cancer is the most common cancer in urban India, but no study has been carried out on psychosocial disorders in breast cancer patients. AIMS: The present study has been undertaken to evaluate behavioural and psychosocial impacts before and after treatment of women with breast cancer. SETTINGS AND DESIGN: The study was carried out in a reputed hospital in Delhi. PATIENTS AND METHODS: A total of 97 breast cancer patients matched for age and economic status were divided into group A (66) and group B (31) on the basis of treatment modalities offered to the patient. These women were interviewed, before and after the treatment, and the observations were recorded in a pre-tested structured questionnaire. STATISTICAL ANALYSIS: Chi-square test and Fisher's exact test were used to calculate statistical significance. RESULTS: Although the extent of sociobehavioral disorders were higher in patients on postoperative adjuvant chemotherapy and radiotherapy when compared with those on postoperative adjuvant chemotherapy alone, the difference was, however, not statistically significant. Psychological reactions were observed in 31% of patients but after intervention, 65% showed adjustment within 4 to 12 weeks, whereas the rest showed late adjustments. CONCLUSIONS: Breast disfigurement and sexuality were found to be least important, but psychological and social support appears to significantly influence the treatment outcome and rehabilitation of breast cancer patients in India. PMID- 20587908 TI - Evaluation of colposcopy vs cytology as secondary test to triage women found positive on visual inspection test. AB - BACKGROUND: Colposcopic evaluation and guided biopsy is an important diagnostic step and standard of management for abnormal cytology smears in developed countries. AIM: The present study evaluates the performance of colposcopy vs conventional cytology in estimating the presence and grade of cervical disease against the reference standard of histopathology as a secondary test modality to triage women found positive on primary screening by visual inspection with 5% acetic acid (VIA). SETTINGS AND DESIGN: Colposcopy and directed biopsy were performed after primary screening for cervical cancer in an urban hospital cancer screening clinic between January 2000 and June 2005, in Mumbai, India. MATERIALS AND METHODS: Healthy women (8863) in the age group of 35-65 years participated in the cervical cancer early detection program in the hospital and community cancer screening clinics in Mumbai. Women found positive on the primary screening test by VIA underwent diagnostic evaluation by Pap smear cytology and colposcopy evaluation with directed biopsies. STATISTICAL ANALYSIS: Accuracy parameters and their 95% confidence intervals were calculated using 2 X 2 tables and standard formulae. RESULTS: The test range of sensitivity of colposcopy for the detection of histologically confirmed cervical intraepithelial neoplasia grade 1+ (CIN1+) or CIN2+ was 58.0-74.7% and that of specificity was 57.5-92.9%. The sensitivity and specificity of cytology to detect CIN2+ was 57.4% and 99.4%, respectively. CONCLUSION: Colposcopy is a good sensitive test for the detection of CIN and can be considered as a secondary testing tool to triage women found positive on VIA. PMID- 20587907 TI - Role of Ki-67 as a proliferative marker in lesions of thyroid. AB - BACKGROUND: Specific criteria are used to diagnose thyroid neoplasms; however, the distinction between certain neoplasms, such as follicular adenoma and carcinoma, could be difficult. Thus, additional diagnostic features that can assist in this distinction would have great clinical usefulness. AIMS: To evaluate the role of the proliferative marker Ki-67 in nonneoplastic and neoplastic lesions of the thyroid, with a special emphasis on the distinction between follicular adenoma and follicular carcinoma. SETTINGS AND DESIGN: A retrospective study from a tertiary care center. MATERIALS AND METHODS: One hundred cases of thyroid lesions, including 50 nonneoplastic and 50 neoplastic lesions, were retrieved from the archives of the Department of Pathology, Pt. BD Sharma PGIMS, Rohtak, Ki-67 immunostaining was performed by peroxidase antiperoxidase method and compared with mitotic counts. RESULTS: Ki-67 labeling index (LI) showed a progressive rise from multinodular goiter to benign to malignant neoplasms. A statistically significant difference was observed in Ki-67 counts between multinodular goiter vs papillary carcinoma (P < 0.05) and follicular adenoma vs follicular carcinoma (P < 0.05). The correlation between mitotic counts and Ki-67 LI was found to be significant. CONCLUSIONS: In the present study, Ki-67 was found to be useful in differentiating between follicular adenoma and follicular carcinoma, but since the sample size of our study was small, larger studies are needed to confirm this observation as well as to assign a cutoff value for differentiating benign from malignant tumors. PMID- 20587909 TI - Hepatoblastoma: experience from a single center. AB - BACKGROUND: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. AIMS: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. SETTINGS AND DESIGN: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. MATERIALS AND METHODS: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. RESULTS: There were 9 boys and 3 girls, aged 5 60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. CONCLUSIONS: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy. PMID- 20587910 TI - Association of gastric cancer incidence with MDR1 gene polymorphism in an ethnic Iranian population. AB - BACKGROUND: The allele frequency of the multidrug resistance 1 (MDR1) gene C3435T polymorphism differs with different ethnic populations, such as Asian, African, and Caucasian. This polymorphism has been reported to be associated with the increase of gastric cancer. OBJECTIVES: The objective of this study was to find out the association of gastric cancer incidence with MDR1 gene polymorphism in an ethnic Iranian population. MATERIALS AND METHODS: In this study, 48 gastric cancer patients were diagnosed. Genomic DNA was extracted by a salting-out method. The MDR1 polymorphism was studied by a polymerase chain reaction (PCR) restriction fragment length polymorphism method, using a standard method. RESULTS: The polymorphic homozygote (T/T) genotype showed significantly an association with the incidence of gastric cancer compared with controls (P < 0.05). CONCLUSIONS: This study suggests that C3435T polymorphism of the MDR1 gene may be associated with gastric cancer in an ethnic Iranian population. PMID- 20587911 TI - Incidence rate of ovarian cancer in Iran in comparison with developed countries. AB - BACKGROUND: Ovarian cancer is one of the most common gynecologic malignancies. The present study was designed to compare age-standardized incidence rate (ASR) of ovarian cancer in Iran with that in Australia and some other developed countries. MATERIALS AND METHODS: Data from the Cancer Registry Program of Iran, as a base, were compared with the cancer registry reports of surveillance, epidemiology and end results program in the USA, considering the population of the USA in the year 2000 as the standard population. RESULTS: In all the age groups, ASR of ovarian cancer was much lower in Iran. Overall rates of ovarian cancer in Iran and the USA were 3.9 and 16.2 per 100,000, respectively. CONCLUSION: Age-standardized ovarian cancer rate in Iran was much lower in comparison with high incidence areas in the world. Encouraging oral contraceptive use and reduction in fat intake may be effective in decreasing the rate of ovarian cancer or keeping its rate constant in Iran. PMID- 20587912 TI - Prevalence and pattern of nodal metastasis in pT4 gingivobuccal cancers and its implications for treatment. AB - CONTEXT: The pattern of nodal spread in oral cancers is largely predictable and treatment of neck can be tailored with this knowledge. Most studies available on the pattern are from the western world and for early cancers of the tongue and floor of the mouth. AIMS: The present study was aimed to evaluate the prevalence and pattern of nodal metastasis in patients with pathologic T4 (pT4) buccal/alveolar cancers. SETTINGS AND DESIGN: Medical records of the patients with pT4 primary buccal and alveolar squamous cell carcinomas treated by single stage resection of primary tumor and neck dissection at Gujarat Cancer and Research Institute (GCRI), Ahmedabad, a regional cancer center in India, during September 2004 to August 2006, were analyzed for nodal involvement. MATERIALS AND METHODS: The study included 127 patients with pT4 buccal/alveolar cancer. Data pertaining to clinical nodal status, histologic grade, pT and pN status (TNM classification of malignant tumors, UICC, 6th edition, 2002), total number of nodes removed, and those involved by tumor, and levels of nodal involvement were recorded. Statistical analysis was performed using the Chi-square test. RESULTS: Fifty percent of the patients did not have nodal metastasis on final histopathology. Occult metastasis rate was 23%. All of these occurred in levels I to III. Among those with clinically palpable nodes, level V involvement was seen only in 4% of the patients with pT4 buccal cancer and 3% of the patients with alveolar cancer. CONCLUSIONS: Elective treatment of the neck in the form of selective neck dissection of levels I to III is needed for T4 cancers of gingivobuccal complex due to a high rate of occult metastasis. Selected patients with clinically involved nodes could be well served by a selective neck dissection incorporating levels I to III or IV. PMID- 20587913 TI - From two-dimensional to three-dimensional conformal radiotherapy in prostate cancer: an Indian experience. AB - BACKGROUND: Sparse data from India are available regarding the outcome of prostate cancer treatment. We report our experience in treating prostate cancer with radiotherapy (RT). MATERIALS AND METHODS: This study included 159 men with locally advanced cancer treated with RT with or without hormone therapy between 1984 and 2004. The median RT dose was 70 Gy over 35 fractions. Eighty-five patients received whole pelvic RT and prostate boost, and 74 patients were treated with 3-dimensional conformal radiotherapy (3DCRT) to prostate and seminal vesicles alone. RESULTS: The median follow-up was 25 months and the freedom from biochemical failure for all the patients at 5 years was 76%, disease-free survival (DFS) 59.1%, and overall survival (OAS) was 70.1%. The risk stratification (91% vs 52%, P < 0.03) and RT dose (72.8% for dose > 66 Gy vs 43.5% for dose < 66 Gy; P = 0.01) affected the DFS. DFS at 5 years was better in the group receiving 3DCRT to prostate and seminal vesicles (78% vs 51.5%; P = 0.001) and was reflected in OAS as well (P = 0.01). CONCLUSION: CRT technique with dose escalation results in significant benefit in DFS and OAS in locally advanced prostate cancer. PMID- 20587914 TI - Important vaccines used as tools for tertiary prevention in oncology patients. AB - For the prevention of many diseases, vaccination is considered to be a good method. At present, a number of vaccines are available. The concept of vaccination for oncology patients as a tertiary prevention protocol was introduced recently. A literature review on this topic was performed. For reviewing, the author used the electronic search for the keyword "vaccine" and "cancer" on PubMed for inclusion of the previously published articles and further search of reference papers on vaccines as tools for tertiary prevention in oncology patients was done. In this article, the important vaccines for oncology patients are briefly discussed. There are many interesting vaccinations that are useful for tertiary prevention in oncology patients. PMID- 20587915 TI - Cervical cancer screening in developing countries. PMID- 20587916 TI - Mixed epithelial and stromal tumor of the kidney. PMID- 20587917 TI - Squamous cell carcinoma arising in mature cystic teratoma: a rare case. PMID- 20587918 TI - Unusual presentation of multiple myeloma. PMID- 20587919 TI - Intracystic papillary carcinoma in a male breast following mastectomy for infiltrating ductal carcinoma. PMID- 20587920 TI - Surgical misadventure of transecting tumor infiltrated infrarenal vena cava in a patient of Wilms tumor. PMID- 20587921 TI - Myelomatous pleural effusion: a diagnostic challenge. PMID- 20587922 TI - Aggressive angiomyxoma of female vulva. PMID- 20587923 TI - Does delay in lymphadenectomy alone influence the survival in carcinoma penis? PMID- 20587924 TI - Current management of Parkinson's disease. AB - Although Parkinson's disease (PD) is still incurable, a large number of different treatments have become available to improve the quality of life and physical and psychological morbidity, and its early treatment is of prime importance. This article reviews the current situation of PD. This review was based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. The subject headings and keywords used were Parkinson's disease and therapeutic advances. Only articles written in English were included.The management of PD has evolved rapidly over the last 10 years with the advent of new drugs and new classes of drugs, but the currently available treatment methods are all symptomatic ones. However, some of these may have marginal disease-modifying effects. Progress in manufacture of newer drugs has markedly improved the treatment of early PD; however, the management of advanced Parkinson's symptoms remains a challenge. Currently no treatment has been proven to slow the progression of PD. Although symptomatic therapy can provide benefit for many years, PD will eventually result in significant morbidity. PMID- 20587925 TI - Microalbuminuria and its relations with serum lipid abnormalities in adult Nigerians with newly diagnosed hypertension. AB - BACKGROUND: Microalbuminuria (MA) has been associated with increased risk of adverse cardiovascular events in nondiabetic hypertensive patients. This may be partly due to increased serum lipid abnormalities in these patients. The objective was to evaluate the association between MA and serum lipid abnormalities in nondiabetic adult Nigerians with hypertension. MATERIALS AND METHODS: A prospective study which recruited 96 consecutive newly diagnosed adult Nigerian hypertensive met the study criteria. These patients were compared with the same number of age- and sex-matched healthy normotensive individuals. RESULTS: 52 (54.2%) and 44 (45.8%) of patients were males and females, respectively. Mean +/- SD ages were 51.2 +/- 10.1 and 48.2 +/- 8.8 years for male and female patients, respectively. Microalbuminuria was more than five times more prevalent in the patients than in the controls. The means +/- SD serum total cholesterol (5.0 +/- 0.56 vs. 4.05 +/- 0.50 mmol/L, P = 0.04) and low-density lipoprotein cholesterol (3.99 +/- 0.49 vs. 2.84 +/- 0.58 mmol/L, P = 0.001) were significantly higher, while the mean +/- SD for high-density lipoprotein cholesterol was (0.91 +/- 0.16 vs. 1.04 +/- 0.13 mmol/L, P = 0.03) significantly lower in microalbuminuric patients than in non-microalbuminuric patients. CONCLUSION: This study has shown that adult nondiabetic Nigerians with MA are significantly more likely to have dyslipidemia than patients without MA. Hence, this subset of hypertensive patients constitutes a high risk group. Screening for MA, and early recognition and prompt treatment of serum lipid abnormalities in these patients may reduce the risk of adverse cardiovascular events. PMID- 20587926 TI - Internet and medical student in Marrakech. AB - BACKGROUND: The implementation of ICT in the academic curriculum is a part of the e-reform of the undergraduate education currently ongoing at the Moroccan medical school. In order to evaluate the efficiency of such reform, the authors have conducted a survey at the Marrakech school of medicine including 200 students. MATERIALS AND METHODS: A comparison between the third year medical students and sixth year medical students was performed in our university Hospital. RESULTS: The majority of the students have a personal computer and internet access. Our study shows no significant differences between third year medical students and sixth year medical students. In both students' groups the level of internet and computer access, the internet skills, the opinions on internet use and ICT implementation and the difficulties encountered when using internet for medical purpose were similar. This can be explained by the lack of no implementation of ICT in our university. CONCLUSION: The learning process is still based on traditional methods. Educational authorities have to train students to improve their internet skills. PMID- 20587927 TI - Metallic foreign body in esophagus: are multiple radiographs necessary? AB - BACKGROUND: Multiple X-rays required for confirmation and localization of ingested metallic foreign body preoperatively predisposes children to increased radiation exposure. This study aims to highlight the current necessity or otherwise of these X-ray requests. MATERIALS AND METHODS: This is a retrospective study of patients with ingested metallic foreign bodies over a five-year period in a tertiary health institution. Case notes and X-ray requests were studied. RESULTS: Of 39 cases of foreign body in esophagus, 29 (74.4%) were metallic and the coin accounted for 79.3% of all metallic foreign bodies. There were 20 males to 9 females and 28 children aged 2 months to 11 years to one adult. There were 62 pre-extraction X-rays consisting of 29 (46.8%) initial confirmatory films and 33 (53.2%) repeat films for localization of the foreign body. There were 10 post extraction films for postoperative complications. CONCLUSION: More than half of the X-ray films were unnecessary and the radiation exposure was avoidable if alternative methods of localization of the foreign body such as the handheld metal detector were available. PMID- 20587928 TI - Obstetric management after infertility treatment. AB - OBJECTIVE: King Fahd University Hospital, Al-Khobar is a tertiary care center without the facility for in-vitro fertilization (IVF) and embryo transfer, but ovulation induction (OI) is done routinely. The objective of this analysis was to study the obstetric outcome of patients who conceived after IVF and OI. DESIGN: Retrospective analysis. PATIENTS AND METHODS: One hundred and twenty patients were analysed within the study period of January 1996 and December 2006. Patients were divided into two groups viz; those who became pregnant after IVF and embryo transfer and those who conceived after OI. The obstetric outcome measures analysed include: antenatal and intrapartum complications, the number of babies delivered and the mode of delivery. The data was entered into the database and analysed using SPSS Inc. version 14. RESULTS: The average age was 37.31 +/- 4.1 years (range 21-43 years), primary infertility was seen in 74 women and secondary infertility in 46 patients. In 73 (60.8%) of the women, pregnancy occurred after OI and the rest of the patients underwent IVF at other centers. Sixty-nine (57.5%) of women had no previous pregnancy. Antenatal complications were similar in both groups but intrapartum complications were significantly higher in IVF group, P = 0.05. Multiple pregnancies were significantly higher in the IVF group (P = 0.001). Normal vaginal deliveries (NVD) were common in the OI group, and cesarean sections (CS) was significantly higher in IVF group (P = 0.001). CONCLUSION: This study shows that in pregnancy after IVF and embryo transfer, intrapartum complications were more and CS was the common mode of delivery when compared with those that had only OI. PMID- 20587929 TI - Depot medroxyprogesterone injectable contraception at the University of Uyo Teaching Hospital, Uyo. AB - BACKGROUND: Depot medroxyprogesterone acetate is the most studied injectable contraceptive and also one of the most effective methods of contraception currently available. It is reversible, its use is independent of intercourse, and can be provided by trained non-medical staff making it particularly suitable for use in developing countries. The aim of this study is to determine the socio demographic characteristics of its acceptors, the timing of use and complications at the University of Uyo Teaching Hospital, Uyo. MATERIALS AND METHODS: The record cards of all clients who accepted medroxyprogesterone acetate injectable contraception over a nine-year period were studied. RESULTS: There were 1065 new contraceptive acceptors out of which 166 (15.1%) accepted depot medroxyprogesterone acetate. The modal age group of the clients was 30-34 years (35.0%). Majority of clients were grandmultiparous (63.9%), married (82.0%), and 50.6% had primary level education. Majority of the clients (84.2%) derived their sources of information on contraception from clinic personnel and friends/relatives. All the clients received their injections within seven days of menstruation. The most common side effects were amenorrhea (12.0%) and spotting of blood per vaginam (10.8%). CONCLUSION: Depot medroxyprogesterone acetate is a safe form of contraception, which was mostly accepted by grandmultiparous women and those in their thirties. The involvement of the print and electronic media in the propagation of accurate information about depot medroxprogesterone acetate to members of the community and the introduction of post-abortal and puerperal administrations of depot medroxyprogesterone acetate and its new formulation; depo sub-Q provera in all our hospitals are advocated. PMID- 20587930 TI - Acute sigmoid volvulus in a West African population. AB - BACKGROUND: Acute sigmoid volvulus is one of the commonest causes of benign large bowel obstruction. Its incidence varies considerably from one geographic area to another. This study reviews its management in a relatively high-prevalence area. MATERIALS AND METHODS: All adult patients with acute sigmoid volvulus seen at the Royal Victoria Teaching Hospital (RVTH), Banjul, between September 2000 and January 2005 were retrospectively studied. Demographic data, clinical features, resuscitative measures, results of investigations, findings at surgery and postoperative course, and complications were retrieved from the patients' clinical records and analyzed. RESULTS: A total of 48 patients, 45 (93.8%) males and 3 (6.3%) females, with a male: female ratio of 14.3:1, age range of 19 to 78 years and mean age of 45.8 +/- 17.6 years underwent treatment for acute sigmoid volvulus. Twenty-one (43.8%) of the patients were aged 40 to 49 years. Two (4.2%) had rectal tube detortion followed by elective sigmoidectomy and primary anastomosis on the same admission, while 24 (50%) had emergency laparotomy, at which bowel decompression, one-stage resection and primary anastomosis without on table lavage were done. The rest of the patients, 22 (45.8%), had gangrenous sigmoid colons at laparotomy and consequently underwent resection and Hartmann's procedure. Fourteen (29.1%) patients developed wound infection; and 5 (10.4%) had prolonged ileus, which was managed conservatively. There was no anastomotic leak. The mean hospital stay was 11.1 days. There were 5 deaths, giving a mortality rate of 10.4%. CONCLUSION: Acute sigmoid volvulus in The Gambia is almost exclusively a male disease. Sigmoid colectomy and primary anastomosis can be carried out safely in those with viable colon without on-table colonic lavage. PMID- 20587931 TI - Residency training program: perceptions of residents. AB - BACKGROUND: There is a phobia among doctors for the residency training program, since the establishment of the program over 30 years ago. The reason for establishing the program was mainly to provide the much-needed specialists in medicine. OBJECTIVES: To ascertain the perception of the residency training program among residents. MATERIALS AND METHODS: Structured questionnaires were administered to residents at 3 training institutions in Nigeria. RESULTS: One hundred nineteen (85.5%) questionnaires were returned out of 140. The ages of respondents ranged from 27 to 42 years, the median age being 30 years. There were 110 males and 9 females. One hundred six (89.1%) were junior residents. Ninety (75.6%) were sponsored by the training institutions. Seventy-four (62.25%) felt their consultants were contributing just 50% or less to their training. Sixty-two (52.2%) of the respondents had attended a revision course, conference or seminar within the last 6 months. Majority of the residents would want better remuneration, up-front payment of examination and revision fees, more teaching by the consultants and less emphasis on the provision of services as ways of improving the program. CONCLUSION: Majority of the residents are sponsored by the training institutions. PMID- 20587932 TI - Misdiagnosis of tuberous sclerosis in a Nigerian girl: a case report and review of literature. AB - Tuberous sclerosis is a rare neuro-cutaneous syndrome, one of the phakomatosis, characterized by facial angiofibromas (adenoma sebaceum), mental retardation and epilepsy. This classic triad occurs in less than one half of patients, probably in one-third, thus requiring a high index of suspicion to diagnose. Consequently it may easily be misdiagnosed as neurofibromatosis or other medical conditions. This is a case report of tuberous sclerosis in a 13-year-old Nigerian girl that was misdiagnosed as neurofibromatosis because of her cutaneous lesions. This paper discussed the case and reviewed the literature. A comprehensive medical clerkship, thorough physical examination, high index of clinical suspicion and neuroimaging investigations are required to confirm diagnosis. PMID- 20587933 TI - Acute cholestatic hepatitis along with agranulocytosis: a rare side effect of carbimazole. AB - Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well but some may develop life threatening side effects such as agranulocytosis, aplastic anemia and cholestatic hepatitis. A 45-year-old female was diagnosed with severe hyperthyroidism. Treatment with Carbimazole 30 mg/day was initiated. Within six weeks following the start of therapy, patient developed potentially life-threatening acute cholestatic hepatitis and agranulocytosis as adverse effects to carbimazole. The patient's symptoms and laboratory abnormalities resolved following withdrawal of offending drug. Agranulocytosis and cholestatic hepatitis together is an extremely rare idiosyncratic side effect of Carbimazole treatment and considered to be dose and age-related. Antithyroid drugs are deceptively easy to use, but because of the variability in the response of patients and the potentially serious side effects, all practitioners who prescribe the drugs need to have a working knowledge of their complex pharmacology. PMID- 20587934 TI - Authorship of a research publication. PMID- 20587935 TI - Pattern of drug utilization in rural Malaysia. PMID- 20587936 TI - Fibrocalculous pancreatic diabetes in a Nigerian patient. PMID- 20587937 TI - Vitamin C and the treatment of tetanus. PMID- 20587940 TI - Candida spp. in periodontal disease: a brief review. AB - Although the main reservoir of Candida spp. is believed to be the buccal mucosa, these microorganisms can coaggregate with bacteria in subgingival biofilm and adhere to epithelial cells. Such interactions are associated with the capacity of Candida spp. to invade gingival conjunctive tissue, and may be important in the microbial colonization that contributes to progression of oral alterations caused by diabetes mellitus, some medications, and immunosuppressive diseases such as AIDS. In addition, immune deficiency can result in proliferation of Candida spp. and germination of forms that are more virulent and have a higher capacity to adhere to and penetrate cells in host tissues. The virulence factors of Candida spp. increase host susceptibility to proliferation of these microorganisms and are likely to be important in the study of periodontal disease. Herein, we briefly review the literature pertaining to the role of Candida spp. in periodontal disease, and consider the main virulence factors, the host immune response to these microorganisms, and the effect of concomitant immunosuppressive conditions. PMID- 20587941 TI - Curing efficiency of high-intensity light-emitting diode (LED) devices. AB - We evaluated the curing efficiency of 4 high-intensity light-emitting diode (LED) devices by assessing percentage of residual C=C (%RDB), surface microhardness (SM), depth of cure (DC), percentage of linear shrinkage-strain (%LS), and percentage of wall-to-wall contraction (%WWC). The light-curing units tested were a QTH light, the Elipar TriLight (3M/ESPE), and 4 LED devices - the Allegro (Denmat), the Bluephase (Ivoclar/Vivadent), the FreeLight2 (3M/ESPE), and The Cure TC-01 (Spring Health Products). The %RDB was measured by microFTIR spectroscopy. Microhardness measurements (Vickers) were performed at the surface (H0) and at depths of 3 mm (H3) and 5 mm (H5) of cylindrical specimens. Depth of cure was expressed as the ratio of microhardness at each depth, relative to the corresponding surface value (H3/H0 and H5/H0). The bonded disc method was used to evaluate %LS. For the %WWC evaluation, cylindrical resin restorations were imaged by high resolution micro-CT and the %WWC was calculated at depths of 0 mm and 2 mm. There were no statistical differences among the LEDs in %RDB or %LS. The Bluephase and Allegro had the highest SM values. As compared with the other LEDs, the Bluephase and The Cure TC-01 had lower values for depth of cure at depths of 3 mm and 5 mm. There were no significant differences in %WWC among the LEDs at either depth, and the QTH had the lowest %WWC at both depths. PMID- 20587942 TI - Relationship between initial crowding and interproximal force during retention phase. AB - This study investigated the change in interproximal force (IPF) in mandibular anterior teeth during retention and the relationship between the irregularity index before orthodontic treatment and the IPF. The effect that an erupting third molar had on IPF was also examined. Forty treated patients (40 with extraction of four bicuspids) were followed for 18 months during the retention phase. The irregularity index was determined from initial plaster casts. The total IPF was determined by measuring the interdental frictional forces at the mandibular anterior teeth by withdrawing a metal strip. The total IPF increased during the retention phase until 18 months, and there was a positive correlation between the irregularity index and total IPF 6 to 18 months after active treatment. An erupting third molar did not affect the total IPF. An increase in the total IPF may be an indication of relapse in mandibular anterior crowding. In conclusion, orthodontists should pay special attention to potential relapse in the lower anterior teeth 6 months after active treatment in cases with severe anterior crowding before treatment. PMID- 20587943 TI - A comparative study of microfocus CT and histomorphometry in the evaluation of bone augmentation in rat calvarium. AB - Microfocus computed tomography (micro-CT; R_mCT) is a dynamic noninvasive method for measuring bone regeneration. This study evaluated whether R_mCT was equivalent to histomorphometry in assessing bone augmentation. Two plastic caps of graft material with (experiment) or without hydroxyapatite (HA; control) were placed in the exposed calvaria of rats. Images of bone augmentation within the plastic caps were then taken using R_mCT. Histological sections were cut along the same plane as that used for the micro-CT images. Bone regeneration beyond the skeletal envelope occurred at both the experimental and control sites. Bone volume also increased at both sites. In addition, consistent patterns of bone formation were observed in both R_mCT and histological images. R_mCT analysis enables highly quantitative and qualitative measurement of bone augmentation in living animals. PMID- 20587944 TI - Genetic study of gutter-shaped root (GSR) in AKXL RI mouse strains using QTL analysis. AB - In this study, quantitative trait locus (QTL) analysis was used to identify candidate chromosomes and for detecting the regions that include the gene or genes causing gutter-shaped root (GSR) in AKXL recombinant inbred mouse strains. One potential QTL was detected on chromosome 5 within a region of 13.0 cM, where the likelihood ratio statistic (LRS) score was higher than a suggestive level. This indicates that one of the candidate genes causing mouse GSR may be located in this region. PMID- 20587945 TI - Endothelin-1 regulates rat bone sialoprotein gene transcription. AB - Endothelin-1 (ET-1) was originally discovered as a vasoconstrictor protein excreted by vascular endothelial cells. Recently, tumor-produced ET-1 has been considered to stimulate osteoblasts to form new bone, and to be an important mediator of osteoblastic bone metastasis. ET-1 has high affinity for two different membrane receptors, ET(A)R and ET(B)R, which are expressed by many types of cells including osteoblasts. Bone sialoprotein (BSP) is a phosphorylated and sulfated glycoprotein associated with mineralized connective tissues. To investigate the effects of ET-1 on BSP transcription, we used rat osteoblast-like ROS17/2.8 cells. Levels of BSP and osteopontin mRNA were increased at 12 h after treatment with ET-1 (10 ng/ml), and ET-1 at the same concentration induced luciferase activity of a -116 to +60 BSP promoter construct at 6 h. Transcriptional activity of -84BSPLUC, which contains the cAMP response element (CRE), was increased by ET-1. Furthermore, at 6 h, ET-1 (10 ng/ml) increased the binding of nuclear protein to CRE, the FGF2 response element (FRE) and the homeodomain protein-binding site (HOX). Antibodies against CREB1, JunD and Fra2 disrupted the formation of CRE-protein complexes, while antibodies against Runx2 and Dlx5 reduced the formation of FRE- and HOX-protein complexes. These findings indicate that ET-1 increases BSP transcription via the CRE, FRE and HOX sites in the rat BSP gene promoter. PMID- 20587947 TI - Detection of nucleoproteins in squamous cell carcinoma, and dysplastic and normal mucosa in the oral cavity by methyl green-pyronin staining. AB - Squamous cell carcinoma (SCC) is the most malignant neoplasm of the oral cavity. The mortality rate associated with head and neck cancers remains high, and thus detection techniques are important. In the present study, methyl green-pyronin staining was applied to 5 normal mucosa specimens, 10 cases of dysplastic mucosa, 12 cases of SCC (grade I), 10 cases of SCC (grade II) and 5 cases of SCC (grade III) in the oral cavity. This is the first study in which nuclear and nucleolar cytomorphometric parameters (diameter, area and number) in such oral lesions were evaluated using this method. As methyl green-pyronin selectively stains nucleic acids, it can differentiate between DNA (green) and RNA (red). The results reveal that the proposed method can be used to evaluate changes in the nucleus and nucleolus in premalignant lesions in the oral cavity. PMID- 20587946 TI - Butyric acid stimulates bone sialoprotein gene transcription. AB - Butyric acid (sodium butyrate; BA) is an extracellular metabolite secreted from periodontopathic bacteria present in subgingival plaque. BA induces apoptosis of T and B cells, and acts as a potent inhibitor of histone deacetylases. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, and may be crucial for osteoblast differentiation, bone matrix mineralization and tumor metastasis. In the present study we investigated the regulation of BSP transcription by BA in rat osteoblast-like ROS17/2.8 cells. At 12 h, BA (10(-4) M) increased the level of BSP mRNA, and enhanced the luciferase activity of the construct pLUC3, which includes the promoter sequence between nucleotides -116 and +60. Transcriptional stimulation by BA was abrogated in the pLUC3 construct which containing a 2-bp mutation in the fibroblast growth factor 2 response element (FRE). Gel shift analyses showed that BA increased the binding of nuclear protein to FRE. These data suggest that BA increases the transcription of the BSP gene mediated through FRE in the rat BSP gene promoter, and induces osteoblast activity in the early stage of bone formation. PMID- 20587948 TI - Rubber dam use among a subpopulation of Nigerian dentists. AB - In this cross-sectional questionnaire-based study, we surveyed the attitudes toward, knowledge of, and use of rubber dams (RDs) among dentists in southern Nigeria. The questionnaire, which was distributed and collected by one of the authors, requested information on the dentists' background characteristics, attitudes, and knowledge. Data were analyzed with SPSS, and the chi-square was used to assess differences in categorical variables. A total of 100 out of 108 dentists responded (92.6% response rate). The prevalence of RD use was 18%. Dentists in the government sector used RDs more often than did dentists in the private sector. About 77% of dentists had not used RDs or were unaware of how to use them. All specialists had seen RDs, but only 56% had used one in their practice. All dentists believed in the effectiveness of RDs. We conclude that rubber dams are underutilized in this population, and that dentists need to be made aware of the possibility of rubber dam use through an awareness campaign. PMID- 20587949 TI - Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. AB - Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage. PMID- 20587950 TI - Prevalence of enamel pearls in teeth from a human teeth bank. AB - Enamel pearls are anatomical structures that can bring about clinical implications if associated with the retention of plaque, in turn resulting in periodontal disease. In an attempt to avoid periodontal disease, the removal and treatment of these enamel pearls, may be a necessity in some circumstances. A total of 45,785 extracted teeth from a human teeth bank were analyzed for the presence of enamel pearls. The most prevalent anatomical location of enamel pearls was the permanent maxillary first and second molar region. An association between the prevalence of enamel pearls and dental class (P < 0.001) was observed, most frequently in the maxillary molars. In the maxillary molars, the most prevalent anatomical location of enamel pearls in the first and second molars was the furcation between the distobuccal and palatal roots. Enamel pearls are a common observation in molars in general, but are most commonly found in maxillary molars. PMID- 20587951 TI - Study of the effect of surface treatment on the long term effectiveness of tissue conditioner. AB - Adequate softness and surface integrity are the two most important clinical features of a tissue conditioner. This study was designed to examine the effect of coating on the surface integrity and softness of a tissue conditioner at various time intervals. A total of 72 specimens were prepared and divided into two equal groups. Group I (control group) specimens were lined with tissue conditioner and left uncoated. Group II (test group) specimens were lined with tissue conditioner and coated with a surface conditioning agent. The specimens were then examined for softness with a durometer and for surface integrity with a scanning electron microscope (SEM) at the baseline, and after 1, 2 and 3 weeks. At 3 weeks, softness on the American Standards for Testing Materials (ASTM) scale showed a significant (P < 0.001) difference between the control and test groups. Qualitatively, SEM analysis indicated that surface integrity in the control group had deteriorated by the end of the first week, whereas that in the test group remained intact until the end of the third week. Within the limitations of this study, our data suggest that application of a coating can significantly reduce the loss of softness and surface integrity of a tissue conditioner. PMID- 20587952 TI - Oral squamous cell carcinoma: an analysis of 1,564 cases showing advances in early detection. AB - The present study aimed to detect possible differences in the data of oral squamous cell carcinomas (OSCC) cases diagnosed in a Dental School in Sao Paulo city over the last 40 years. The records of patients diagnosed as having OSCC between the years 1960 and 2008 were retrieved. The whole period was divided into four time periods. A total of 1,564 cases were reviewed. The variables analyzed were: sex, age, race, anatomical site, lesion duration, and lesion size. The chi square test was used for statistical analysis. Overall, males were more affected than females (3:1), but when comparing the first and last time periods, the ratio decreased significantly (5.8:1 to 2.8:1). A significant increase in the rate of OSCC in patients over 80 years was observed in the last time periods. The gingiva was the most affected site, but the frequency of lower lip involvement increased in the last time period. Regarding lesion size and duration of symptoms at the time of diagnosis, there was a significant difference between the first and last time periods. Smaller lesions were found and the time of lesion development was shorter in the last few years of the study. These findings support the optimistic view that, in recent years, earlier diagnosis has resulted from early oral cancer detection in Sao Paulo city. PMID- 20587953 TI - Correlation between mucoepidermoid carcinoma grade and AgNOR count. AB - Mucoepidermoid carcinoma (MEC) is a malignant glandular epithelial neoplasm having an unpredictable behavior and a tendency to recur. Numerous parameters have been assessed to predict the outcome of this lesion, but have been deemed inadequate, with the exception of tumor stage and grade. In the present study, we attempted to correlate the proliferative activity of MEC with its histopathological grade, using argyrophillic nuclear organizer region (AgNOR) count. Thirty cases of MEC were included in the study. All the slides were stained using hematoxylin and eosin and silver nitrate techniques. Counting was performed at a magnification of x1,000 with an oil-immersion lens. Positive correlations were seen between AgNOR count and MEC grade (P < 0.05), with AgNOR count increasing in proportion with tumor grade. The AgNOR count in various grades of MEC indicates a relative progression in the proliferative activity of this tumor. This index is positively correlated with tumor grade, although there are some exceptions. The utility of AgNOR count in predicting the prognosis of MEC can be considered of importance; however, further assessment, such as survival studies, is necessary. PMID- 20587954 TI - Comparative study of the sealing ability of the lateral condensation technique and the BeeFill system after canal preparation by the Mtwo NiTi rotary system. AB - The purpose of this in vitro study was to compare the sealing ability of the lateral condensation technique and the BeeFill system after canal preparation by the Mtwo rotary system. Forty extracted single-rooted teeth were prepared by using the Mtwo rotary system. The teeth were then divided into 2 experimental groups (n = 15 each) and 2 control groups (n = 5 each). The specimens in groups 1 and 2 were obturated using the lateral condensation technique and the BeeFill system, respectively. The teeth in the negative control group were also obturated with the lateral condensation technique, and the specimens in the positive control group were not root-filled. The specimens were then immersed in an aqueous solution of 2% China ink for 1 week, after which the roots were cleared and the linear extent of dye penetration was measured with a stereomicroscope by 2 endodontists. The data collected were then analyzed by using the 1-sample Kolmogorov-Smirnov test and independent t test, with a significance level of P < or = 0.05. Although the mean (+/- standard deviation) dye leakage in the BeeFill thermoplasticized injection group was less than that in the lateral condensation group (1.497 +/- 0.7 vs. 2.521 +/- 1.733), there was no significant difference between the experimental groups on the parametric independent t-test (P = 0.209). PMID- 20587955 TI - Appropriate electrode placement site for electric pulp testing of anterior teeth in Nigerian adults: a clinical study. AB - Electric pulp testing is one of the pulp vitality tests which aid dentists in diagnosis of the pulp status. This test is technique sensitive and hence may elicit false responses. There are some concerns regarding the optimal placement of the probe tip. The threshold value (the lowest electric current at which sensation is perceived) is reached when an adequate number of nerve fibers are stimulated, so the sensation would be greatest where the density of neural distribution is the highest. The purpose of this study was to identify the optimum site for electrode placement in anterior teeth of adults, the threshold values of these teeth using an electric pulp test, and to determine the influence of sex, age, and arch on the outcome. The optimum electrode placement sites and threshold values varied with type of tooth and arch. The maxillary teeth, canines, male gender and increasing age required higher electric current to evoke a sensation, while incisal edges required lower current to evoke a sensation. PMID- 20587956 TI - Comparative study of the concentration of salivary and blood glucose in type 2 diabetic patients. AB - The objective of the present study was to comparatively evaluate the concentrations of blood and salivary glucose as well as salivary flow and xerostomia in type 2 diabetic and non-diabetic patients. The mean salivary glucose level in diabetic patients was 14.03 +/-16.76 mg/dl and 6.35 +/- 6.02 mg/dl (P = 0.036) in the control group. The mean capillary blood glucose level in diabetic patients was 213 +/- 88 mg/dl, while that in non-diabetic patients was 99 +/- 14 mg/dl (P = 0.000). The mean value for resting salivary flow was 0.21 +/ 0.16 ml/min in diabetic patients and 0.33 +/- 0.20 ml/min in the control group (P = 0.002). The stimulated salivary flow was lower in the group of diabetic patients, with a mean of 0.63 +/- 0.43 ml/min, whereas the control group showed a mean of 1.20 +/- 0.70 ml/min (P = 0.000). Of the diabetic patients, 45% exhibited hyposalivation, in contrast to 2.5% of the non-diabetic patients (P = 0.000). Xerostomia was reported in 12.5% of diabetic patients and 5% of non-diabetic patients (P = 0.23). We can conclude that salivary glucose concentration was significantly higher in the experimental group and that there was no correlation between salivary and blood glucose concentrations in diabetic patients. The total salivary flow was significantly reduced in diabetic patients and there was no significant difference as to the presence of xerostomia in both groups. PMID- 20587957 TI - Relation of soluble RANKL and osteoprotegerin levels in blood and gingival crevicular fluid to the degree of root resorption after orthodontic tooth movement. AB - The aim of the present study was the determination of the levels of osteoprotegerin and soluble RANKL in blood serum and in gingival crevicular fluid relative to the degree of orthodontic root resorption in a rat model. Blood samples and gingival crevicular fluid were collected from fourteen 6-month-old male Wistar rats weighing 350-500 g. A 25-g closed orthodontic coil spring was inserted between each upper right first molar and the upper incisors. After 21 days of loading, both upper first molars (treated and control) were extracted and studied under microcomputed tomography scanning. Statistical analysis demonstrated a positive linear correlation between the initial concentration of RANKL in blood serum and the degree of root resorption. The ratio of the initial concentrations of osteoprotegerin to RANKL in blood serum proved to be an independent prognostic factor of the degree of root resorption. The initial concentration of RANKL in gingival crevicular fluid showed a negative correlation to the initial concentration of RANKL in blood serum and for a finite range of initial concentrations of osteoprotegerin in gingival crevicular fluid, the dental root seemed protected against extreme external root resorption. Finally, the concentration of osteoprotegerin in blood serum decreased significantly in cases of severe root resorption. PMID- 20587958 TI - Natal primary molar: clinical and histological aspects. AB - The authors report a case of natal primary molar in a healthy 14-day-old child. The diagnosis of the case and the treatment plan are discussed, as well as histological analyses of the natal tooth. The tooth presented an immature appearance, with high mobility and insertion only in soft tissue, and therefore the clinical option adopted was dental extraction. Histological analyses revealed enamel hypoplasia and dentin showing a typical tubular pattern without alterations. The soft tissue had young and richly vascularized pulp with areas of chronic inflammatory infiltration. PMID- 20587959 TI - Hemifacial microsomia: a clinicoradiological report of three cases. AB - Hemifacial microsomia is a congenital malformation in which there is deficiency in the amount of hard and soft tissues on one side of the face. It is primarily a syndrome of first and second branchial arches involving underdevelopment of the temporomandibular joint, mandibular ramus, masticatory muscles, ears and occasionally defects in facial nerve and muscles. Here, we report three cases of hemifacial microsomia diagnosed based on clinical and radiographic findings. All three cases had variable presentations ranging from the mildest form that included facial asymmetry and ear deformity to the most severe and unusual form with facial nerve paralysis and spine deformity. PMID- 20587960 TI - Single-session use of mineral trioxide aggregate as an apical barrier in a case of external root resorption. AB - External root resorption may occur as a consequence of trauma, orthodontic treatment, bacterial infection or incomplete sealing of the root canal system (bacterial re-infection), and lead to crater formation on the resorbed apex. This would deform the root apex surface, and cause loss of apical constriction. Depending on the extent of the resorptive process, different treatment regimens have been proposed. A 34-year-old male patient presented with an intra-radicular retainer and an inadequate filling on tooth #21, as well as a radiographic image suggesting periapical bone rarefaction. After root canal retreatment, the defect was accessed coronally. The resorption area was chemo-mechanically debrided and since the apical end was very wide, a calcium sulphate matrix was made. Mineral trioxide aggregate (MTA) was used to fill the resorptive defect, and the coronal access was temporarily sealed. After 24 h, the quality of the apical seal was evaluated with the aid of an operating microscope, and then the root canal system was filled. A 12-month follow-up radiograph showed adequate repair of the resorption. Clinically, the tooth was asymptomatic. We concluded that MTA can be successfully used to avoid overextension of the filling material when treating a tooth with external resorption. PMID- 20587961 TI - An estimate of the rate of growth of a juvenile aggressive ossifying fibroma in a 15 year old child. AB - Juvenile ossifying fibroma (JOF) is an uncommon fibro-osseous lesion occurring in the facial bones. It has been recognised as a separate histopathological entity among the fibro-osseous group of lesions. Fibro-osseous lesions of the craniofacial bones are difficult to classify and treat however a common factor to all is the conversion of the bone to benign fibrous tissue with a varying degree of mineralised tissue. This case describes a 15 year old patient with a juvenile aggressive ossifying fibroma (JAOF) and an estimate of the rate of growth of such a rare lesion. PMID- 20587962 TI - Chondroectodermal dysplasia (Ellis-van Creveld syndrome): a case report. AB - Ellis-van Creveld (EVC) syndrome is a form of skeletal and chondroectodermal dysplasia, occurring with and without systemic involvement. Taurodontism of permanent and primary molars and upper posterior supernumerary teeth are rarely associated with this syndrome. A 5-year-old girl presented with early childhood caries and hypodontia. She had labiogingival adhesion, labiogingival frenulum hypertrophy, accessory labiogingival frenula, and a serrated appearance of the gingiva. She was also short in stature. All major features of chondroectodermal dysplasia were present. EVC syndrome requires multidisciplinary therapeutic planning, and the dentist plays a fundamental role in management of the oral and dental manifestations. PMID- 20587963 TI - Dental management of oculodentodigital dysplasia: a case report. AB - Oculodentodigital dysplasia is an extremely rare autosomal dominant pleiotropic disorder. The syndrome is characterized by abnormal facial features, central nervous system involvement, syndactyly and clinodactyly of fourth and fifth fingers, dry and lusterless hair, generalized enamel hypoplasia and odontodysplasia. Combination of odontodysplasia, poor oral hygiene, and parental neglect can lead to extensive destruction of tooth structure and the treatment options become limited. Early diagnosis with a proper treatment plan and meticulous oral hygiene program helps eliminate the necessity of multiple tooth extractions. This case report describes the comprehensive dental treatment aimed at rehabilitation of function and aesthetics of the dentition in an 8-year-old boy with oculodentodigital dysplasia. PMID- 20587964 TI - Stevens-Johnson syndrome: a case report. AB - Non-steroidal anti-inflammatory drugs are commonly prescribed in dental practice after minor oral surgical procedures such as tooth extraction. Diclofenac sodium is one of the non-steroidal anti-inflammatory drugs widely used for pain relief in dentistry. Although adverse reactions to these drugs are rare, at times they can cause a life-threatening phenomenon. Stevens-Johnson syndrome is one such potentially lethal adverse drug reaction. Most reported cases of analgesic induced Stevens-Johnson syndrome were due to oxicams or propionic acid derivatives. There are very few detailed reports of Stevens-Johnson syndrome due to use of diclofenac. We report here a case of Stevens-Johnson syndrome which occurred due to use of diclofenac sodium. The clinical features of this condition and multidisciplinary management of the patient are described in brief. PMID- 20587965 TI - Clinical efficacy of a novel elimination diet composed of a mixture of amino acids and potatoes in dogs with non-seasonal pruritic dermatitis. AB - There has been a need for improvement of the elimination diet used for diagnosis of adverse food reaction (AFR) in dogs. Recently, a novel elimination diet composed of a mixture of amino acids and potatoes was developed. We evaluated the efficacy of the elimination diet for diagnosis of AFR in dogs. Twenty dogs that were suspected to have allergic dermatitis were enrolled in a 2-month food elimination trial using the diet. Before and after the trial, the clinical symptoms were evaluated based on the change in canine atopic dermatitis extent and severity index (CADESI), pruritus score and medication score. Of the 20 dogs, 15 completed the food elimination trial. The remaining 5 dogs were removed from the trial because of diet unpalatability, skin disease progression or diarrhea. On the basis of evaluation of the clinical scores, we observed that the clinical symptoms improved in 11 of the 15 dogs that completed the food elimination trial. Provocative challenge was performed in 10 of the 11 dogs that showed improvement in their clinical symptoms. Of the 10 dogs, 7 were diagnosed as having AFR against food ingredients such as pork, beef, chicken and wheat because their skin symptoms reappeared after intake of these ingredients. The results of the food elimination trial and the provocative challenge indicated the usefulness of the novel elimination diet for diagnosis of AFR. PMID- 20587966 TI - Assessment of cognitive function before and after surgery for posterior cranial fossa lesions using computerized and conventional tests. AB - Cognitive function has not been well studied after neurosurgery for posterior fossa lesions despite its potential importance in determining surgical indications and approaches. The present study evaluated changes in cognitive functions after posterior fossa surgery to detect any differences between the middle cranial fossa and lateral suboccipital approaches in 50 patients with posterior fossa lesions such as tumors and vascular diseases. Twenty-five patients underwent surgery via the middle fossa and 25 via the lateral suboccipital approaches. Computerized test battery (CogState) and conventional neuropsychological tests (serial seven-word learning test and mini-mental state examination) were examined before, 1 month after, and 3 months after surgery. All scores of the neuropsychological tests remained within normal limits after surgery. However, the scores of one computerized test battery and serial seven word learning tests decreased significantly 1 month after surgery and recovered within 3 months, indicating temporary deterioration of short-term memory in the middle fossa group. The computerized tests detected significantly larger numbers of patients with worsened results than the conventional tests. The middle fossa approach and operation time showed correlations with the postoperative neuropsychological declines. The computerized tests could be performed easily and were beneficial for detecting subtle changes of the cognitive function after surgery. Cognitive function, especially short-term memory, may decline temporarily with the middle fossa approach and long operation time. PMID- 20587967 TI - Optimal dose of plasmid vascular endothelial growth factor for enhancement of angiogenesis in the rat brain ischemia model. AB - Vascular endothelial growth factor (VEGF) administration has recently been assessed as a therapeutic strategy for ischemic diseases including brain ischemia because of its angiogenic effect. However, VEGF also causes detrimental adverse effects by increasing vascular permeability. This study examined whether plasmid human VEGF (phVEGF) administration induced angiogenic effects in the rat brain ischemia model caused by permanent ligation of both common carotid arteries, and investigated the occurrence of adverse effects. Administration of various doses (0-200 microg) of phVEGF in the temporal muscle was followed by encephalo-myo synangiosis. Thirty days after treatment, the numbers and areas of capillaries per field in the extracted brains were analyzed with the National Institutes of Health Image software program. The maximal angiogenic effect occurred with a 100 microg dose of phVEGF in the numbers and areas of capillaries in the VEGF-treated brains. Histological examination showed no apparent adverse effects in the brain parenchyma even at the highest administration dose (200 microg) of phVEGF. The maximal angiogenic effect at the optimal dose of phVEGF can be considered under the threshold to cause serious adverse effects in the rat brain. PMID- 20587968 TI - Acute lung injury associated with systemic inflammatory response syndrome following subarachnoid hemorrhage: a survey by the Shonan Neurosurgical Association. AB - Acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS) is a systemic complication following subarachnoid hemorrhage (SAH), but the incidence and influence on prognosis are unclear. The incidences of SIRS and ALI were surveyed in a prospective multicenter study of 96 patients admitted for SAH between December 2004 and June 2007. Hunt and Hess grade and Glasgow Outcome Scale score were also investigated. Forty-eight patients were diagnosed with SIRS, and 26 developed ALI within 4 weeks of admission. Nineteen of the 26 patients with ALI were complicated by SIRS, and 7 developed only ALI. Thirteen of the 19 patients complicated by SIRS and ALI died, and this mortality was higher than for patients with only SIRS (3/29) and only ALI (1/7). Multivariate analysis of the development of SIRS and/or ALI and Hunt and Hess grade as risk factors associated with aggravation of the outcome showed that complication with SIRS and ALI had the highest risk. Half of the patients admitted for SAH developed SIRS, and more than 25% developed ALI. The prognosis for patients complicated by SIRS and ALI was poor, which indicates that prevention and active treatment of these two pathologies are important. PMID- 20587969 TI - Clinical analysis of spinal cord injury with or without cervical ossification of the posterior longitudinal ligament, spondylosis, and canal stenosis in elderly head injury patients. AB - Patients with degenerative diseases of the cervical spine, such as ossification of the posterior longitudinal ligament, spondylosis, and canal stenosis, sometimes present with acute spinal cord injury caused by minor trauma. However, the relative risk of cervical cord injury with these diseases is unknown. The clinical and radiological features of 94 elderly patients with head injury, 57 men and 37 women aged from 65 to 98 years (mean 76.6 years), were retrospectively analyzed to assess the association of spinal cord injury with degenerative cervical diseases. Degenerative cervical diseases were present in 25 patients, and spinal cord injury was more common in the patients with degenerative diseases (11/25 patients) than in the patients without such diseases (3/69 patients; relative risk = 10.2). The incidence of degenerative cervical diseases seems to be increasing in Japan because life expectancy has increased and the elderly are a rapidly growing part of the population. A fall while walking or cycling is a common mechanism of head injury and/or cervical cord injury in the elderly. To decrease the occurrence of cervical myelopathy, prevention by increasing social awareness and avoiding traffic accidents and falls is important. PMID- 20587970 TI - Ruptured internal carotid artery aneurysm at the origin of a perforating artery associated with a hyperplastic anomalous anterior choroidal artery--case report. AB - A 65-year-old man presented with a hyperplastic anomalous anterior choroidal artery (AChA) associated with a ruptured internal carotid artery aneurysm at the origin of a perforating artery manifesting as sudden onset of headache and vomiting. The aneurysm was too small for endovascular embolization, so we performed open surgery via the left pterional approach. Aneurysm clipping with preservation of the perforator was impossible, so we clipped the aneurysm neck and sacrificed the perforator. We also performed dome clipping because dome puncture resulted in continuous bleeding. Head computed tomography obtained 3 days after the operation showed cerebral infarction at the territory of the sacrificed perforator, but the patient suffered no neurological deficits. This case of internal carotid artery aneurysm with a perforating artery arising from the aneurysm dome shows that sacrifice of the perforator may be necessary to prevent rebleeding. PMID- 20587971 TI - Mixed pial-dural arteriovenous malformation in the anterior cranial fossa--two case reports. AB - Most arteriovenous malformations (AVMs) associated with the meningeal artery in the anterior cranial fossa are the pure dural type, and mixed pial-dural AVMs are rare. Two types of mixed pial-dural AVM occur in the anterior cranial fossa according to the shunting point: one with the nidus in the brain parenchyma of the frontal lobe, and the other with the shunting point in the dura mater. We describe two patients with AVMs fed by the anterior ethmoidal arteries and the persistent primitive olfactory artery, with the nidus located in the pure brain parenchyma of the inferior aspect of frontal lobe, and drained via an abnormal cortical vein into the cavernous and superior sagittal sinuses. The importance of occluding the venous outflow to obliterate intracranial dural arteriovenous fistula (AVF) is emphasized. However, removal of the nidus in the brain parenchyma is required. The presence of a pial feeder should be considered before diagnosis of dural AVF of the anterior cranial fossa, and preoperative detailed evaluation for the pial supply and shunting point is mandatory. PMID- 20587972 TI - Reversible hemianopsia caused by mechanical compression of the visual pathway by the dilated draining vein of an arteriovenous malformation--case report. AB - A 41-year-old woman presented with progressive hemianopsia caused by compression of the lateral geniculate body by the dilated basal vein draining a contralateral frontal arteriovenous malformation (AVM). Magnetic resonance (MR) imaging revealed left frontal AVM and right lateral geniculate body compression due to the dilated basal vein. Emergent presurgical transarterial embolization and surgical removal were performed. Left hemianopsia completely recovered 3 months after surgery and MR imaging indicated improvement of the compression of the lateral geniculate body. Direct mechanical compression of the enlarged drainage vein is one of the causes of homonymous hemianopsia. Early surgical treatment is recommended to obtain a rapid recovery. PMID- 20587973 TI - Delayed subdural hematoma after epidural blood patching in a patient with spontaneous intracranial hypotension--case report. AB - A 51-year-old woman presented with a rare case of spontaneous intracranial hypotension (SIH) complicated by a delayed subdural hematoma (SDH) that required surgical evacuation 2 months after epidural blood patching (EBP). Subdural fluid collections are common among patients with SIH. These fluid collections vary in appearance from thin subdural hygromas to rare large SDHs associated with significant mass effect. Most subdural fluid collections can be safely managed by conservative treatment or EBP. The present clinical course and imaging findings illustrate the possible sequential complications of EBP in patients with SIH. PMID- 20587975 TI - Thoracic vertebral cavernous hemangioma in a schizophrenic patient--case report. AB - A 55-year-old man presented with gait disturbance, incontinence, and back pain. He had a medical history of schizophrenia for the past 35 years. Computed tomography (CT) and magnetic resonance imaging suggested thoracic vertebral hemangioma. Dynamic CT incidentally detected a hepatic hemangioma. Laminectomy of T3 and T4, resection of the epidural hemangioma, and rigid instrumentation between T1 and T6 using rod and hook systems were performed. Postoperatively, his symptoms completely disappeared and the histological diagnosis was capillary hemangioma. Schizophrenic patients have diminished sensitivity to pain or other symptoms, so neurological symptoms may become severe. However, early and appropriate treatment can result in satisfactory neurological outcome. The patient had a rare association of vertebral hemangioma and hepatic hemangioma, which may be a chance occurrence. PMID- 20587974 TI - Infantile chronic subdural hematoma infected by Escherichia coli--case report. AB - A 6-month-old boy presented with a rare case of infected subdural hemorrhage manifesting as sustained fever and focal seizure. The boy had been well without contributory medical history. Physical examination found no neurological impairment with intact superficial appearance and soft fontanels. The parents denied recent head trauma or shaking injury. Blood examination was normal except for white blood cell count of 19200/microl and C-reactive protein level of 6.7 mg/dl. Bacterial culture of nasal swab, urine, stool, and venous blood samples was negative. Cerebrospinal fluid examination showed normal findings. Cranial computed tomography revealed an expansive subdural fluid collection in the right frontotemporal region. Magnetic resonance imaging showed the lesion as hypointense on T1- and hyperintense on T2-weighted images with intense enhancement of the outer membrane. The patient underwent burr-hole drainage, which identified the subdural hematoma encapsulated in a thick outer membrane and intermingled with pus material. Culture of the pus identified Escherichia coli. The patient received antibiotic therapy for 8 weeks that resulted in complete resolution of the infection. We assumed that preexisting subdural hematoma formed after minor head trauma was followed by hematogenous infection by E. coli. Infected subdural hematoma is possible in infants presenting with subdural hemorrhage with clinical symptoms of bacteremia. PMID- 20587976 TI - Xanthogranuloma of the sellar region--case report. AB - A 55-year-old woman presented with a rare xanthogranuloma of the sellar region after complaining of severe headache and visual disturbance 3 months previously. Clinical examination showed she was alert with early signs of bitemporal hemianopsia. Endocrinological examination revealed hypopituitarism. Magnetic resonance imaging showed an intrasellar mass extending into the suprasellar region and compressing the optic chiasma, which appeared homogeneously hyperintense on T(1)-weighted images. Endonasal transsphenoidal resection of the tumor was performed. Histological examination disclosed granulomatous tissue with cholesterol clefts, hemosiderin deposits, fibrous tissues, and macrophages containing rich fat. The histological diagnosis was xanthogranuloma of the sellar region. Her visual symptoms recovered postoperatively although the hypopituitarism remained. Xanthogranuloma of the sellar region is rare, but must be considered in the differential diagnosis of tumors of the sellar region. PMID- 20587977 TI - Pure intracerebral mass lesion of adult T-cell leukemia/lymphoma--case report. AB - A 48-year-old female presented with a rare case of adult T-cell leukemia/lymphoma (ATL) occurring as only intracerebral mass lesion manifesting as progressively worsening headaches, transient mild weakness of the left lower extremity, bilateral papilledema, and left homonymous hemianopsia. Laboratory examination showed transient leukocytosis (15900/microl) without febrile episode or elevation of C-reactive protein. Neuroimaging revealed a solitary enhanced mass lesion in the right occipital lobe adjacent to the choroid plexus with prominent perifocal edema. The patient underwent gross total removal, and the histological diagnosis was intracerebral ATL. She underwent radiation therapy and chemotherapy after local recurrence and metastasis to an optic nerve. The lesions had disappeared on magnetic resonance imaging with contrast medium 10 months after onset and no recurrence was detected even 5 years later. Intracerebral ATL should be considered in the differential diagnosis of intracerebral mass without leukemia or systemic lymphoma. PMID- 20587978 TI - Large hypothalamic hamartoma with calcification and cystic components in an adult -case report. AB - A 24-year-old female presented with an unusual case of hypothalamic hamartoma manifesting as seizure. Neuroimaging findings were atypical, showing the large tumor (maximum diameter, 50 mm) with a cystic component and calcification. Surgery was performed and histological examination demonstrated heterotopia. Hamartoma should be considered in the differential diagnosis of a suprasellar, non-enhanced mass attached to the hypothalamus. Excessive unnecessary surgery should be avoided, and intraoperative pathological examination may lead to enhanced assessment and better outcomes. PMID- 20587979 TI - Metastatic skull base tumor from thymic carcinoma mimicking Tolosa-Hunt syndrome. AB - A 39-year-old male without contributory medical history had sustained progressive double vision, ptosis, and trigeminal pain for 2 weeks. Physical examination revealed total ophthalmoplegia and visual field defect with normal blood examination and chest radiography. Cranial computed tomography revealed a hyperdense mass in the left frontotemporal fossae with bony erosion. Magnetic resonance imaging confirmed a broad-based, intensely enhanced extraaxial tumor of 4x4x4 cm diameter with dural tail sign. Cerebral angiography demonstrated insignificant blood supply both from the internal carotid and middle meningeal arteries. Nearly total tumor resection was achieved via orbitofrontotemporal craniotomy. Intraoperative findings revealed the extraaxial tumor with broad attachment to the dura mater and invasion to the optic and oculomotor nerves. Histological examination revealed hypercellular tumor with significant cell atypism, mitotic activity, and focal necrosis. Immunohistochemical staining was positive for AE1/3 and c-kit, but negative for glial fibrillary acidic protein. Systemic examination performed postoperatively revealed a thymic tumor without additional remote lesions. The final diagnosis was metastatic brain tumor from thymic carcinoma. Rapid progression of neurological impairment inconsistent with a benign extraaxial tumor needs prompt surgical intervention. PMID- 20587980 TI - Chondrosarcoma with atypical clinical presentation treated by gamma knife radiosurgery for multiple brain metastases--case report. AB - A 60-year-old male was first treated for World Health Organization (WHO) grade II chondrosarcoma arising from the ring finger manifesting as painful swelling. Four years later, the patient presented with cerebral infarction. Echocardiography revealed a tumor occupying the left atrium. He underwent open heart surgery and the tumor was identified as metastatic chondrosarcoma with malignant transformation to WHO grade III lesion. Five months following the cardiac surgery, the patient suffered generalized seizure. Cerebral magnetic resonance imaging revealed multiple parenchymal lesions. Surgical tumor extirpation confirmed the histological diagnosis as metastatic grade III chondrosarcoma. Gamma knife radiosurgery (GKS) performed postoperatively controlled the parenchymal lesions for more than 10 months without relapse. GKS may be effective for the treatment of brain metastasis from high grade chondrosarcoma. PMID- 20587981 TI - Pure germinoma of the pineal gland with synchronous spinal dissemination--case report. AB - An 11-year-old boy presented with pineal pure germinoma with spinal dissemination manifesting as a 1-month history of ocular motility disturbance and a history of abnormal sensations in the left leg persisting for several months. His past medical history was unremarkable. Craniospinal magnetic resonance imaging showed an enhanced tumor in the pineal gland and widespread leptomeningeal dissemination in the spinal canal. Biopsy of the pineal tumor was performed. Histological examination revealed a pure germinoma. Chemotherapy with carboplatin and etoposide in combination with radiotherapy induced complete remission of the tumors. He regained normal eye movement and sensation in his left leg during the chemotherapy period. Germinomas with dissemination are generally more malignant and refractory than solitary germinomas, but this patient showed a strong response to chemoradiotherapy. PMID- 20587982 TI - Acquired intraventricular arachnoid cyst of the third ventricle--case report. AB - A 35-year-old male showed slow progression of dilation of the lateral ventricles and third ventricle. He had undergone surgery for third ventricular colloid cyst and ventriculoperitoneal shunting when he was 3 years old. Computed tomography revealed progression of triventricular dilation. He underwent endoscopic fenestration of the arachnoid cyst and endoscopic third ventriculostomy. The postoperative course was good. Arachnoid cysts within the third ventricle are rare. Endoscopic treatment of an arachnoid cyst within the third ventricle is less invasive and effective for arachnoid cysts within the third ventricle associated with hydrocephalus. PMID- 20587983 TI - Middle cranial fossa arachnoid cyst presenting with subdural effusion and endoscopic detection of tear of the cyst--case report. AB - A 15-year-old boy presented with a case of middle cranial fossa arachnoid cyst associated with subdural effusion and manifesting as headache and vomiting after minor head injury. Computed tomography disclosed a cystic lesion in the left middle cranial fossa and ipsilateral subdural effusion. Fundoscopic examination revealed papilledema. A small tear of the cyst wall was confirmed endoscopically. Fenestration of the cyst was performed under the operating microscope. Postoperative course was uneventful. The tear in the outer wall of an arachnoid cyst may suggest the mechanism of occurrence of subdural effusion associated with middle cranial fossa arachnoid cyst. PMID- 20587984 TI - Linezolid treatment for intracranial abscesses caused by methicillin-resistant Staphylococcus aureus--two case reports. AB - Two patients were treated for intracranial infections involving methicillin resistant Staphylococcus aureus (MRSA). A 30-year-old woman was admitted to our hospital for intracerebral hemorrhage related to arteriovenous malformation. After decompressive craniectomy, the patient developed an epidural abscess. MRSA was isolated from the pus culture. The infection did not improve after intravenous vancomycin (VCM) administration for 15 days. However, after administration of linezolid (LZD) for 14 days, the infection had improved, and the white blood cell count and C-reactive protein values had normalized. A 53 year-old woman had previously undergone 3 operations for craniopharyngioma before the age of 35 years. She was admitted to our hospital with fever and disturbance of consciousness. Magnetic resonance imaging with contrast medium revealed a brain abscess caused by MRSA. After 14 days of intravenous administration of VCM, the infection had not improved and intravenous administration of LZD was initiated. After administration of LZD for 14 days intravenously and 14 days orally, the infection had improved, and the white blood cell count and C-reactive protein values had normalized. VCM is highly effective against MRSA infection, but penetration into the central nervous system (CNS) is poor. LZD has good CNS penetration, so should be considered for secondline antibiotic therapy for VCM resistant intracranial MRSA infection. PMID- 20587985 TI - Endoscopic endonasal trans-sphenoidal optic nerve decompression for traumatic optic neuropathy--technical note. AB - The endoscopic endonasal trans-sphenoidal approach can decompress the traumatized and swollen optic nerve without brain retraction. Three cases of traumatic optic neuropathy (TON) were treated by this endoscopic approach. We performed 58 endoscopic endonasal trans-sphenoidal approaches in 52 patients between April 2006 and December 2007. Three patients, 2 men and a woman aged 42-66 years, with TON were treated by endoscopic endonasal trans-sphenoidal optic nerve decompression. Adequate decompression of the optic canal was observed in all three patients. Two experienced improved visual function, but the third did not. No surgical complications were observed in any patient. We were able to reach the optic canal above the opticocarotid recess near the orbit. Endoscopic endonasal trans-sphenoidal optic canal decompression using a navigation system may be a safe and effective surgical strategy in carefully selected patients with TON. PMID- 20587986 TI - Limb salvage--at which costs, which risks? PMID- 20587987 TI - Comparison of frontomaxillary facial angles using both 2D and 3D ultrasound at 11+0 to 13+6 weeks of gestation. AB - INTRODUCTION: The aim of this study is to (i) directly compare both two dimensional (2D) and three-dimensional (3D) frontomaxillary facial angle (FMFA) in first trimester, and (ii) to assess the ease with which both may be performed. MATERIALS AND METHODS: Both 3D volumes of the fetal head and 2D fetal profiles were collected from 251 consenting patients during routine first-trimester nuchal translucency (NT) screening. The FMFA in 2D was measured at the time of the NT screening. The 3D FMFA was measured offline. RESULTS: The 2D FMFA was systematically higher than the 3D FMFA. The difference in 3D-2D FMFA was statistically significant from 11+0 to 12+3 weeks. From 12+4 to 13+6 weeks the difference was no longer significant with p = 0.06. Performing the measurement did not unduly increase the time of the study. Even for the experienced sonographer the technique is technically difficult, relying on many factors for accurate caliper placement. DISCUSSION: The 2D FMFA is greater than the 3D angle. This was found in previous studies, but not thought to be statistically significant. The difference decreased with increasing gestational age. There is a learning curve associated with performing this measurement. Normative data for both 2D and 3D, incorporating ethnicity, may be necessary before inclusion in the first-trimester algorithm. PMID- 20587988 TI - Contribution of magnetic resonance imaging to prenatal differential diagnosis of renal tumors: report of two cases and review of the literature. AB - Enlargement of a kidney on prenatal imaging is usually due to hydronephrosis or cystic renal disease, and much less often results from solid tumors such as mesoblastic nephroma, Wilms' tumor, nephroblastomatosis, renal sarcoma, and angiomyolipoma. All can be diagnosed by ultrasound. Magnetic resonance imaging is useful not only in confirming the presence of a renal mass, but also in the evaluation of the contralateral kidney for subtle abnormalities. We present one case each of Wilms' tumor and mesoblastic nephroma, both detected on antenatal ultrasound and further studied with fetal magnetic resonance imaging. PMID- 20587989 TI - Interleukin 4 or cytokine antagonists? Time to change the search for novel psoriasis therapies. PMID- 20587990 TI - Recalcitrant pemphigus vulgaris responding to systemic tacrolimus. AB - Pemphigus vulgaris (PV) is an auto-immune blistering skin disease characterized by flaccid blisters and painful erosions of mucous membranes and skin. Suprabasal blister formation results from a loss of epidermal cohesion induced by auto antibodies against the desmosomal protein desmoglein 3. Treatment of PV currently consists of systemic glucocorticosteroids and adjuvant immunosuppressive drugs such as azathioprine, mycophenolate mofetil, cyclophosphamide or dapsone. Due to the low incidence of PV, there are insufficient data to conclude which treatment is the most effective and safest. Thus far, systemic tacrolimus (FK506, Prograf) has not yet been reported as adjuvant medication for PV. Here, we describe the successful use of systemic tacrolimus in 2 patients with recalcitrant PV of the oral mucosa. Tacrolimus was well tolerated, and clinical improvement allowed tapering of corticosteroids. Thus, oral tacrolimus may be a therapeutic alternative for patients with recalcitrant PV. PMID- 20587991 TI - A hairy paradox: congenital triangular alopecia with a central hair tuft. AB - Congenital triangular alopecia (CTA) is a developmental anomaly characterized by a bald patch involving the temporal region on one or, more rarely, both sides. We report 5 patients with CTA showing a central island of short hair that was categorized as terminal hair both macroscopically and microscopically. The cause of this paradoxical phenomenon is unknown. PMID- 20587992 TI - Spontaneous fading of reticular pigmentation in Naegeli-Franceschetti-Jadassohn syndrome. PMID- 20587993 TI - Visual acuity and heterogeneities of retinal ganglion cell densities and the tapetum lucidum of the African elephant (Loxodonta africana). AB - The eyes of three adult male African elephants were examined, the retinas were whole-mounted, stained and analyzed to determine visual acuity. A range of small to large ganglion cell types were observed across the retinas. We observed three regions of high ganglion cell density, one in the upper temporal quadrant, a visual or horizontal streak and a smaller region at the nasal end of the horizontal streak. The peak density of ganglion cells observed was 5,280/mm(2), and our calculations indicate that the elephant has a maximal visual acuity of between 13.16 and 14.37 cycles/degree. We observed a heterogeneous structure of a tapetum lucidum, the cells of which were found to be most strongly aggregated behind the temporal and nasal densities of retinal ganglion cells. The strength of the tapetum lucidum was weaker posterior to the density of ganglion cells forming the horizontal streak. The morphology of the elephant eye appears to be such that it reflects: (1) the importance of trunk-eye co-ordination for feeding; (2) the importance of 24-hour vigilance for either predators or conspecifics, and (3) the arrhythmic nature of the daily activity of this animal, being useful both diurnally and nocturnally. PMID- 20587995 TI - Interstitial deletion of chromosome 7q and the lack of association with Down syndrome screening markers. PMID- 20587994 TI - Effects of amphetamine on conditioned place preference and locomotion in the male green tree frog, Hyla cinerea. AB - Neural systems mediating motivation and reward have been well described in mammalian model systems, especially with reference to reward properties of drugs of abuse. Far less is known of the neural mechanisms underlying motivation and reward in non-mammals. The behavioral procedure conditioned place preference (CPP) is often used to quantify reward properties of psychoactive drugs. The indirect dopamine agonist d-amphetamine (AMPH) is known for its properties for inducing CPP in mammals and for inducing dose-related stereotypic movements. We used the green tree frog, Hyla cinerea, to examine whether AMPH could induce both CPP and a dose response change in motor behaviors. We demonstrated that H. cinerea can show place conditioning to AMPH following 14 days of training and that AMPH can cause reversal of a strong baseline place preference. Amphetamine treated animals (20 mg/kg b.w.) received the drug paired with the previously non preferred context, and vehicle paired with the preferred context. Control animals received vehicle in both preferred and non-preferred contexts. Amphetamine treated animals switched context preference following conditioning, whereas control animals did not. We also demonstrated in an open-field experiment that AMPH did not cause any noticeable changes in motor movement or behaviors across a range of doses (0, 10, 20 mg/kg b.w.). This study represents the first examination of the behavioral effects of AMPH in amphibians. These results may contribute to a better understanding of the function and pharmacology of a reward system that may mediate natural behaviors in frogs and other vertebrates. PMID- 20587996 TI - Best practice options for hair removal in patients with unwanted facial hair using combination therapy with laser: guidelines drawn up by an expert working group. AB - Hirsutism is a common disorder affecting between 5 and 15% of the population. One of the most devastating consequences of hirsutism is the presence of unwanted facial hair. Treatment of hirsutism involves a two-pronged approach: treating the underlying cause and reduction of visible hair. Laser hair removal is one of the most effective options for reducing visible hair, however, it may not be wholly effective in all patients and combination therapy may need to be considered. Pharmacological therapy is often used in combination with mechanical hair removal due to the time needed for the drug treatment to demonstrate visible results. Clinical data investigating the use of laser treatment in combination with other treatments has focused on laser with topical eflornithine. The expert working group reviews existing data and provides guidance on the use of eflornithine in combination with laser for resistant hirsutism. PMID- 20587997 TI - Nerve growth factor promotes the survival of goat preantral follicles cultured in vitro. AB - The aim of this study was to investigate the effects of nerve growth factor (NGF) on the in vitro culture of goat preantral follicles. Ovarian cortex fragments were cultured in alpha-MEM+ supplemented with 0, 1, 10, 50, 100 or 200 ng/ml NGF for 1 or 7 days. Small fragments of noncultured ovarian tissue as well as those cultured for 1 or 7 days were processed for histology and transmission electron microscopy. The results showed that after 1 or 7 days of culture at all concentrations of NGF, except at 1 ng/ml after 1 day of culture, there was a significant reduction in the percentage of normal follicles compared to noncultured tissues. At higher NGF concentrations (100 and 200 ng/ml) after 7 days of culture, there was a significant reduction in the percentage of normal follicles compared to tissues cultured in alpha-MEM+ alone or at the other concentrations of NGF. It is important to note that ultrastructural and fluorescent analyses confirmed only the integrity of follicles cultured with 1 ng/ml of NGF after 7 days. In contrast to noncultured control tissues, the percentage of developing follicles was significantly increased at all concentrations of NGF after 1 or 7 days of culture. We observed that follicular diameter was greater at 1 and 10 ng/ml NGF after culture for 7 days than at the other concentrations but was similar to follicles cultured in alpha-MEM+ alone. In conclusion, NGF improved the survival of goat preantral follicles cultured in vitro in a dose-dependent manner. PMID- 20587999 TI - Palla's sign and Hampton's hump in pulmonary embolism. PMID- 20587998 TI - Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus. AB - Mechanisms underlying the enhanced virulence phenotype of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are incompletely defined, but presumably include evasion of killing by human polymorphonuclear leukocytes (PMNs or neutrophils). To better understand this phenomenon, we investigated the basis of rapid PMN lysis after phagocytosis of USA300, a prominent CA-MRSA strain. Survival of USA300 clinical isolates after phagocytosis ultimately resulted in neutrophil lysis. PMNs containing ingested USA300 underwent morphological changes consistent with apoptosis, but lysed rapidly thereafter (within 6 h), whereas cells undergoing FAS-mediated apoptosis or phagocytosis induced cell death remained intact. Phagosome membranes remained intact until the point of PMN destruction, suggesting lysis was not caused by escape of S. aureus from phagosomes or the cytolytic action of pore-forming toxins. Microarray analysis of the PMN transcriptome after phagocytosis of representative community associated S. aureus and healthcare-associated MRSA strains revealed changes unique to community-associated S. aureus strains, such as upregulation of transcripts involved in regulation of calcium homeostasis. Collectively, the data suggest that neutrophil destruction after phagocytosis of USA300 is in part a form of programmed necrosis rather than direct lysis by S. aureus pore-forming toxins. We propose that the ability of CA-MRSA strains to induce programmed necrosis of neutrophils is a component of enhanced virulence. PMID- 20588000 TI - Neural respiratory drive in patients with COPD during exercise tests. AB - BACKGROUND: It is unknown whether neural drive is comparable in constant rate and incremental exercise tests. Few data have previously been available to address this question because of the lack of reliable methods to assess neural respiratory drive in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: The aims of this study are to determine whether neural respiratory drive during constant rate exercise differs from that during incremental exercise and to determine whether neural respiratory drive was maximal at the end of exhaustive exercise tests. METHODS: We studied sixteen patients with moderate severe COPD (mean +/- SD FEV(1) 29 +/- 10%). Both diaphragmatic electro-myogram (EMG) and transdiaphragmatic pressure were recorded with a combined multipair electrode balloon catheter during incremental and constant (80% of maximal oxygen consumption derived from a prior incremental exercise test) treadmill exercise. Minute ventilation and oxygen uptake were also measured. RESULTS: Root mean square (RMS) of the diaphragmatic EMG increased gradually without a plateau during incremental exercise, whereas the RMS increased initially and reached a plateau during constant work rate exercise. The RMS of the diaphragmatic EMG at the end of exercise was similar for both incremental and constant work rate exercise (176 +/- 42 MUV vs. 184 +/- 39 MUV); these values were 70 and 73% of maximal values recorded over the study. CONCLUSIONS: The pattern of increase in neural respiratory drive during incremental exercise is different to that observed during constant work rate exercise, but both exercise protocols are terminated when the patients achieve a similar but submaximal drive. PMID- 20588001 TI - Anti-IgE therapy with omalizumab decreases endothelin-1 in exhaled breath condensate of patients with severe persistent allergic asthma. AB - BACKGROUND: Omalizumab is a humanized monoclonal anti-IgE antibody, especially useful for the treatment of severe persistent allergic asthma, inadequately controlled despite regular therapy. OBJECTIVES: The aim of the study was to determine the effect of omalizumab treatment on changes in endothelin-1 (ET-1), which plays an important role in the development of airway inflammation and remodeling in exhaled breath condensate (EBC) in patients with severe asthma. METHODS: The study was conducted in a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to the Global Initiative for Asthma, 2006) and with or without omalizumab (9 vs. 10 patients). Changes in ET-1 in EBC compared with other inflammatory parameters [exhaled nitric oxide - (FE(NO)), blood eosinophil count, and serum eosinophil cationic protein (ECP)] were measured after 16 and 52 weeks of therapy. RESULTS: Omalizumab-treated patients demonstrated a statistically significant decrease in the concentrations of ET-1 in EBC, FE(NO), serum ECP, and blood eosinophil count and an increase in spirometry parameters compared to patients with conventional therapy. In the group of omalizumab-treated patients, statistically significant correlations between the decrease in ET-1 in EBC and a decrease in FE(NO), ECP, and blood eosinophil count as well as the increase in forced expiratory volume in 1 s after omalizumab therapy were revealed. CONCLUSIONS: Our results confirmed that anti-IgE therapy with omalizumab in patients with severe persistent allergic asthma results in decreased expression of ET-1 in the airways. This could be very important in limiting airway inflammation and bronchial structural changes caused by such treatment in asthmatic patients. PMID- 20588002 TI - Noninvasive ventilation in chronic respiratory failure: effects on quality of life. AB - BACKGROUND: Noninvasive ventilation (NIV) has been found to be an essential technique to treat chronic respiratory failure (CRF) resulting from restrictive thoracic disorders (RTD). The last decades were characterized by the expansion of NIV to treat patients suffering from various other conditions, such as chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). OBJECTIVES: The aim of this study was to evaluate the effect of NIV on health related quality of life (HRQoL) of patients with CRF during 2 years and to identify parameters associated with changes in HRQoL. METHODS: Ninety-one patients with CRF [35 COPD; 17 RTD; 28 OHS; 11 neuromuscular diseases (NMD)] participated. HRQoL was assessed with the SF-36 questionnaire. Additional measurements included blood gases, pulmonary function tests, dyspnea, daytime sleepiness, exacerbations and hospitalizations. The patients were evaluated every 3-6 months. RESULTS: Improvements in SF-36 physical component summary (PCS, p < 0.0001) and mental component summary (MCS, p < 0.0001) scores in RTD and MCS in OHS (p = 0.01) and COPD (p = 0.003) were observed by the third month. PCS in OHS and COPD patients improved by the sixth month (p = 0.003 and p < 0.0001, respectively). NMD patients did not present improvements in HRQoL. Improvements in HRQoL were associated with improvements in PaO(2) and dyspnea in COPD patients, and with total hours of daily ventilator use, improvement in dyspnea, pressure support and expiratory positive airway pressure in RTD patients. CONCLUSION: Home NIV is consistently effective in improving HRQoL and physiological parameters in patients with CRF. Randomized trials to identify subgroups of COPD responders are justified by our results. PMID- 20588003 TI - The harmful role of c5a on innate immunity in sepsis. AB - There is accumulating evidence in humans and in experimental sepsis that robust activation of the complement system occurs along with development of defects in the innate immune system. In this report we review evidence that the complement activation product, C5a, appears in the plasma of rodents following cecal ligation and puncture (CLP). C5a interacts with its receptors (C5aR, C5L2) on phagocytes (polymorphonuclear neutrophils, PMNs, macrophages), ultimately paralyzing the ERK1/2 pathway of the mitogen-activated protein kinase signaling pathway. C5a is also interactive with its receptors on a variety of other cell types in various organs. Interaction of C5a with receptors on PMNs results in compromised innate immunity, with intense suppression of phagocytosis, chemotaxis and the respiratory burst. Endothelial cells acquire a pro-inflammatory phenotype (increased ICAM-1 and tissue factor expression), while macrophages are primed and produce large amounts of cytokines/chemokines. All of these outcomes are C5a and C5a receptor dependent. CLP also unleashes activation of clotting (and fibrinolytic) factors in a C5a-dependent manner. Finally, thymocytes upregulate C5aR and react with C5a, resulting in apoptosis via the intrinsic (mitochondrial) pathway. Collectively, these findings suggest that interception of C5a in sepsis preserves innate immune functions and may be a strategy for treatment of septic humans. PMID- 20588004 TI - German cockroach frass proteases modulate the innate immune response via activation of protease-activated receptor-2. AB - Allergen exposure can induce an early innate immune response; however, the mechanism by which this occurs has not been addressed. In this report, we demonstrate a role for the active serine proteases in German cockroach (GC) feces (frass) and protease-activated receptor (PAR)-2 in modulating the innate immune response. A single exposure of GC frass induced inflammatory cytokine production and cellular infiltration in the airways of mice. In comparison, exposure to protease-depleted GC frass resulted in diminution of inflammatory cytokine production and airway neutrophilia, but had no effect on macrophage infiltration. Selective activation of PAR-2 confirmed that PAR-2 was sufficient to induce airway inflammation. Exposure of GC frass to PAR-2-deficient mice led to decreased immune responses to GC frass compared to wild-type mice. Using the macrophage as an early marker of the innate immune response, we found that GC frass induced significant release of tumor necrosis factor-alpha from primary alveolar macrophages. This effect was dependent on the intrinsic proteases in GC frass. We confirmed GC frass-induced cytokine expression was mediated by activation of NF-kappaB and ERK in a macrophage cell line. Collectively, these data suggest a central role for GC frass protease-PAR-2 activation in regulating the innate immune response through the activation of alveolar macrophages. Understanding the potential role of protease-PAR-2 activation as a danger signal or adjuvant could yield attractive therapeutic targets. PMID- 20588005 TI - Urinary bladder tissue engineering using natural scaffolds in a porcine model: role of Toll-like receptors and impact of biomimetic molecules. AB - INTRODUCTION: Natural scaffolds have been shown to induce T helper 2 (TH2) specific immune responses in host tissues; however, the precise mechanisms that underlie this immune response are unknown. Using a porcine animal model, we evaluated the role of Toll-like receptors (TLRs) and matrix remodelling in the implantation of bladder acellular matrix (ACM) grafts and ACMs fortified with biomimetic materials. MATERIALS AND METHODS: Bladders were decellularized with detergent and treated in 3 different ways prior to implantation: ACM alone, hyaluronic acid (HA)-ACM and HA-vascular endothelial growth factor (VEGF)-ACM. Animals were sacrificed at 4 or 10 weeks post-implantation and total gene expressions for TH2 (IL-4), TH1 (IFN-gamma), TLR2, TLR4, and TGF-beta1 were analyzed using real-time RT-PCR. Using histology (H&E and Masson's trichrome) and immunohistochemistry (uroplakin, alpha-smooth muscle actin, CD31 and factor VIII) the regenerative capacity was correlated with the gene expression of different proteins. RESULTS: IL-4, TLR2, and TLR4 gene expression were markedly decreased at 4 and 10 weeks in both the HA-ACM group and the HA-VEGF-ACM group compared to ACM alone. IFN-gamma expression was negligible in all groups and time periods. TGF-beta1 expression was highest in the HA- and VEGF-treated grafts. Recellularization was inversely proportional to TLR and TH2 expression but proportional to TGF-beta1. CONCLUSION: ACM alone grafts demonstrated stronger TLR4 expression which may promote a distinct TH2 immune response and a reduced regenerative capacity in grafts. Treatment of grafts with HA and VEGF may help regulate host immune responses by reducing TLR4 and IL-4 and increasing TGF beta1. PMID- 20588006 TI - Spontaneous resolution of a giant pulmonary bulla in an older woman: role of functional assessment. AB - Pulmonary bullae usually occur as isolated abnormalities in otherwise normal lung tissue or, more frequently, in the presence of emphysema. Pulmonary bullae tend to progressively increase in their size, and spontaneous regressions have very rarely been reported. In this paper, we report the case of an older woman experiencing the spontaneous resolution of a giant pulmonary bulla. Interestingly, the reported case is characterized by a negligible improvement in respiratory function parameters, despite a substantial increase in the 6-min walking test and the oxygen arteriolar partial pressure. PMID- 20588007 TI - With a little help from my spouse: does spousal collaboration compensate for the effects of cognitive aging? AB - BACKGROUND: Collaborating with another person may help people compensate for aging-related losses in memory performance. However, collaborating in itself is effortful and draws upon individual cognitive resources. One factor that can facilitate collaboration, and decrease its resource requirements, is familiarity between interaction partners. Such facilitation should be particularly important when cognitive-mechanic resources are low. OBJECTIVE: The current study was conducted to empirically test this theoretical notion. We hypothesized that cognitive aging should amplify the advantage of collaborating with a familiar partner over collaborating with an unfamiliar person. METHODS: We developed an interpersonal cueing task based on the game Taboo(c). The task modeled an everyday-life situation in which one person cues another person to retrieve a piece of information from memory. Seventy-six younger adults (20-33 years) and 80 older adults (63-79 years) worked on this task once with their spouse and once with an unfamiliar cross-sex partner from the same age group. Collaborative performance was operationalized as the number of cue words needed until the partner guessed the target, as determined by independent trained coders. Performance in the Digit Symbol Substitution Test was used as an indicator of cognitive aging. RESULTS: Multilevel-modeling analyses revealed that collaborating spouses outperformed collaborators who had not known each other before. This effect was comparable for both age groups but larger in persons with lower Digit Symbol scores. While participants with lower Digit Symbol scores generally performed worse in the collaborative task, they partly made up for this difference when working with the spouse. CONCLUSION: We conclude that spousal collaboration may offer a compensatory strategy to cope with individual aging related losses. PMID- 20588008 TI - Malnutrition-inflammation score independently determined cardiovascular and infection risk in peritoneal dialysis patients. AB - BACKGROUND: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome-predictor in maintenance hemodialysis (MHD) patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. METHODS: All chronic stable PD outpatients in the PD center of National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. RESULTS: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had major cardiovascular or infection events. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection events in the multivariate Cox proportional hazard model. For every one unit increase in the MIS, the adjusted hazard ratio for mortality was 1.177 (95% CI 1.050-1.320, p = 0.005). For every one unit increase in the CCI, the adjusted hazard ratio for mortality was 1.180 (95% CI 1.046 1.330, p = 0.007). CONCLUSIONS: MIS can predict fatal and nonfatal cardiovascular and infection events in chronic stable PD patients. The CCI, which is closely associated with the MIS, is an independent determinant of cardiovascular and infection events as well. Interventional studies are indicated to confirm the utility of the MIS in PD populations who undergo nutritional or anti-inflammatory treatments. PMID- 20588009 TI - What infusion flow should be used for mid-dilution hemodiafiltration? AB - BACKGROUND: There is still no consensus on the optimal infusion flow (Qi) in mid dilution hemodiafiltration. The aim of this study was to compare mid-dilution with varying Qi. SUBJECTS AND METHODS: Prospective study in 25 patients who underwent seven hemodialysis sessions with a Qi of 0, 50, 100, 150, 200, 250 and 300 ml/min. RESULTS: All sessions were well tolerated except Qi 300 ml/min. No significant differences in urea, creatinine, alpha(1)-microglobulin or alpha(1) acid glycoprotein reduction ratios were observed. beta(2)-Microglobulin, myoglobin and prolactin reduction ratios were higher with Qi 150, 200, 250 and 300 ml/min in comparison with Qi of 0, 50 and 100 ml/min. There were no differences in the removal of small or larger molecules when Qi was 150 ml/min or higher. CONCLUSIONS: Optimal Qi in mid-dilution appears to be in the range of 150 250 ml/min since good clinical outcomes, similar efficiency and no technical complications up to a Qi of 250 ml/min were observed. PMID- 20588010 TI - Reduction of free immunoglobulin light chains using adsorption properties of hemodiafiltration with endogenous reinfusion. AB - In this work we investigated the acute effects of hemodiafiltration with endogenous reinfusion (HFR therapy) on the removal of free immunoglobulin light chains (FIgLCs), which may be considered members of the family of uremic toxins. In two groups of patients - group 1 (polyclonal FIgLCs production) and group 2 (monoclonal plasma cell proliferative disorders), we analyzed the pre- and postdialysis levels of kappa- and lambda-chains. In group 1 we observed a significant reduction of FIgLCs (p < 0.01). A similar trend was found in patients of group 2 only for kappa-chains. The FIgLCs removal ratio was significantly higher for kappa- than lambda-chains in the two patient groups. In vitro data showed affinity of macroporous resin to binding FIgLCs. Our results show that the HFR therapy could be effective in removing FIgLCs, particularly kappa-chains in dialysis patients with polyclonal and monoclonal FIgLCs production. PMID- 20588011 TI - Modeled dalbavancin transmembrane clearance during intermittent and continuous renal replacement therapies. AB - BACKGROUND/AIMS: Knowledge of dalbavancin renal replacement therapy (RRT) disposition is vital to ensure appropriate dosing. In vitro models of continuous RRT and intermittent hemodialysis (IHD) were used to determine dalbavancin transmembrane clearance (CLtm). METHODS: Dalbavancin saturation and sieving coefficients (SCs) were determined for hemodialysis and hemofiltration therapies, respectively, using various hemodiafilter and effluent rate combinations. Dalbavancin CLtm estimates were calculated from observed saturation and SCs. RESULTS: Saturation and SCs for both modalities of continuous dialysis and hemofiltration and IHD with high permeability hemodiafilters were small. Nonetheless, during continuous RRT with high dialysate and ultrafiltration rates, dalbavancin CLtm (0.20-1.26 ml/min) matched and often exceeded literature-derived dalbavancin renal clearances. Dalbavancin CLtm was undetectable during IHD with low-permeability hemodialyzers, but with high-permeability hemodialyzers, substantial CLtm (1.90-2.43 ml/min) was noted. CONCLUSION: Dalbavancin CLtm is dependent on RRT modality, hemodiafilter, and effluent flow. Dalbavancin doses may need to be adjusted depending on RRT parameters. PMID- 20588012 TI - Blood pressure course in acute stroke relates to baroreflex dysfunction. AB - BACKGROUND: Acute hypertension frequently occurs in acute stroke and is associated with unfavorable outcome. However, despite the high prevalence, the pathophysiology remains unclear. Baroreflex dysfunction has repeatedly been reported in stroke patients. We hypothesize that blood pressure (BP) derangements in the acute phase relate to the impairment of baroreflex. METHODS: We assessed baroreflex sensitivity (BRS) in 109 acute stroke patients with both ischemic and hemorrhagic stroke using the sequential cross-correlation method. Admission BP and BP values derived from continuous 72-hour monitoring were recorded. Demographic and clinical data including stroke volumes and admission NIHSS scores were included into the analysis. RESULTS: The BRS significantly correlated with admission BP (r = -0.24, p = 0.01), with the occurrence of acute hypertension (> or =220mm Hg/ > or = 110 mm Hg) on admission (r = -0.37, p < 0.001) and with the number of episodes with > or =220 mm Hg/> or =110 mm Hg in the first 72 h after admission (r = -0.44, p < 0.001). Admission NIHSS or lesion volume did not correlate with acute hypertension on admission or hypertensive episodes within the first 72 h. In a multivariable model, BRS remained a significant, independent predictor for both the occurrence of acute hypertension on admission and hypertensive episodes within the first 72 h. CONCLUSIONS: In acute stroke, decreased BRS was independently associated with the occurrence of acute hypertension on admission. In addition, BRS seemed to be a valid predictor of the BP course in the first 72 h. As some antihypertensives may ameliorate BRS, therapeutic relevance of this finding warrants further attention. PMID- 20588013 TI - Association of inflammatory markers and carotid intima-media thickness with the risk of cardiovascular events in high-risk patients. AB - OBJECTIVE: Both inflammatory markers and carotid intima-media thickness (IMT) are associated with future cardiovascular disease (CVD). We investigated whether inflammatory markers can be predictors for incident CVD independent of carotid IMT in atherosclerotic high-risk patients and evaluated the joint effect of inflammatory markers and IMT in CVD prediction. METHODS: We performed a prospective cohort study of 770 patients who had one or more atherosclerotic risk factors. Serum high-sensitive C-reactive protein (hsCRP), interleukin (IL)-6, IL 18, and carotid IMT were assessed at baseline and the incidence of CVD was determined. RESULTS: During 4.3 years of mean follow-up, CVD occurred in 104 patients (14%). In univariate analyses, higher levels of hsCRP, IL-6, and IL-18 were significantly related to an increased risk of CVD. However, only IL-6, but not hsCRP or IL-18, was associated with incident CVD after adjustment for conventional risk factors and carotid IMT (hazard ratio of upper half to lower half, 1.87; 95% confidence interval, 1.20-2.93). Measuring IL-6 level in combination with carotid IMT improves the prediction of incident CVD. CONCLUSIONS: Elevated IL-6 is associated with the risk of CVD independently of carotid IMT in atherosclerotic high-risk patients. PMID- 20588014 TI - Symptomatic intracranial atherosclerotic stenoses: prevalence and prognosis in patients with acute cerebral ischemia. AB - BACKGROUND: In Caucasian patients with acute stroke or transient ischemic attack (TIA) due to symptomatic intracranial atherosclerotic stenoses (ICAS), only limited data on the recurrent stroke rate and its associated risk factors have been reported. In view of the increasing options for endovascular interventions, we sought to investigate the prevalence, risk for recurrent stroke and mortality in these patients. METHODS: A total of 304 consecutive patients with acute ischemic stroke or TIA due to 50-99% ICAS were prospectively documented in 19 German stroke centers. In 201 patients (68.1% of the survivors), a central biannual telephone follow-up could assess recurrent stroke and mortality up to a median of 2 years after the index event. RESULTS: An ischemic cerebrovascular event attributable to symptomatic ICAS was found in 2.24% of the consecutively admitted patients. The overall cumulative recurrent stroke rate after admission was 17.9% (95% CI = 13.4-23.5) for the first year and 23.3% (95% CI = 17.8-29.8) over 3 years. After correction for age and sex, only previous stroke (HR = 2.11, 95% CI = 1.14-3.91) and diabetes (HR = 2.41, 95% CI = 1.33-4.37) were significantly associated with recurrent stroke. CONCLUSION: Although the prevalence of this etiology seems very low in patients admitted to German stroke centers, we found a high risk of recurrent stroke in patients with symptomatic ICAS. Whether endovascular interventions can reduce this high risk needs to be determined in a randomized trial. PMID- 20588015 TI - New cerebral lesions on T2*-weighted gradient-echo imaging after cardiac valve surgery. AB - BACKGROUND: It is well known that silent ischemic brain lesions on diffusion weighted imaging (DWI) commonly occur after various interventional procedures or surgeries. However, to our knowledge, postoperative new lesions on T2*-weighted gradient-echo imaging (GRE) have never been explored. METHODS: This prospective observational study enrolled 19 consecutive patients undergoing cardiac valve surgery. Preoperative and postoperative (within 7 days) GRE and DWI were performed. New GRE lesions were defined as signal loss lesions on postoperative GRE which were not observed on preoperative GRE. Long-term follow-up GRE was performed in a limited number of cases. RESULTS: Twelve patients developed 26 small (<10 mm) new GRE lesions. Of these patients, 1 had a generalized seizure accompanied by confusion and facial weakness with DWI lesions, and 1 showed confusion of short duration without DWI lesions. Long-term follow-up GRE was performed 3 years after surgery in 4 patients. Of the 12 new GRE lesions in these 4 patients, 11 lesions were still observable on long-term follow-up GRE. CONCLUSIONS: New cerebral lesions on GRE after cardiac valve surgery are common and are presumed to be rapidly developed microbleeds and mostly asymptomatic. Further studies are needed to investigate the precise nature and clinical implications of new GRE lesions. PMID- 20588016 TI - Hyperintense carotid plaque on T(1)-weighted turbo-field echo MRI in symptomatic patients with low-grade carotid stenosis and carotid occlusion. AB - BACKGROUND: In addition to stenosis grading, magnetic resonance imaging (MRI) may provide valuable information about plaque 'status', e.g. hyperintense vulnerable carotid plaque, associated with higher morbidity and mortality. In the present study, we investigated the prevalence, clinical and radiological correlates of hyperintense carotid plaques on T(1)-weighted turbo-field echo (T(1)w-TFE) MRI in patients with ischemic symptoms. METHODS: A total of 153 patients presenting with transient ischemic attack or ischemic infarct, studied with contrast-enhanced magnetic resonance angiography (CEMRA), were retrospectively examined. Stenosis grade was obtained from CEMRA images, presence or absence of hyperintense carotid plaque from T(1)w-TFE MRI. Stenosis grade and baseline characteristics were compared between patients with and without a hyperintense plaque. RESULTS: Twenty eight patients (18%) showed one or more hyperintense internal carotid (ICA) plaques. Hyperintense plaques were found in patients with <50% stenosis (6 of 158 ICAs), 50-70% stenosis (4 of 11), >70% stenosis (14 of 74) and carotid occlusion (4 of 28). Presence of hyperintense plaque was associated with older age (70 vs. 62 years; p < 0.05), higher prevalence of cardiac disease (61 vs. 28%; p < 0.01), ischemic infarct as presenting symptom (37 vs. 14%; p < 0.01), ischemic cerebral lesions on MRI (63 vs. 32%; p < 0.01), and the ICA on the patients' symptomatic side (70 vs. 42%; p < 0.01). CONCLUSIONS: More than one third of patients with 50 70% stenosis present with a hyperintense plaque. This subgroup of patients could in the future possibly benefit from more aggressive medicinal therapy or revascularization. PMID- 20588017 TI - Can we do more for the STEMI patient than restore coronary blood flow? PMID- 20588018 TI - Rationale and design of the POSTEMI (postconditioning in ST-elevation myocardial infarction) study. AB - Rapid reperfusion of the infarct-related coronary artery is essential in the treatment of acute ST-elevation myocardial infarction (STEMI). Paradoxically, restoration of the blood flow to the ischemic area may result in further injury to the myocardium. This phenomenon is described as 'ischemia/reperfusion injury' and the pathophysiological mechanisms are not fully elucidated. A cardioprotective effect of ischemic postconditioning (short repetitive cycles of reperfusion and re-occlusion) has been demonstrated in experimental studies and in pilot studies on patients with acute STEMI treated with primary percutaneous coronary intervention. We present the study design of the Postconditioning in ST Elevation Myocardial Infarction (POSTEMI) study, which is a prospective, randomized, open-label clinical trial with blinded endpoint evaluation designed to evaluate the effect of postconditioning on final infarct size. Patients with acute STEMI with symptoms of less than 6 h and proximal or mid-coronary artery occlusion will be included. The primary endpoint is infarct size, assessed by cardiac MRI after 4 months. The secondary endpoints are to evaluate the effect of postconditioning on TIMI myocardial perfusion grade, resolution of ST-segment elevation, release of markers of ischemia, left ventricular function and final infarct size related to the area at risk. A total of 260 patients will be included in the study. PMID- 20588019 TI - Design and methodologies of the POSTconditioning during coronary angioplasty in acute myocardial infarction (POST-AMI) trial. AB - BACKGROUND: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. STUDY DESIGN: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 +/- 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. CONCLUSION: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI. PMID- 20588020 TI - Comparison of the effect of preinterventional arterial remodeling on intimal hyperplasia after implantation of a sirolimus- or paclitaxel-eluting stent. AB - BACKGROUND: We compared the effect of arterial remodeling on intimal hyperplasia (IH) after the implantation of a sirolimus-eluting stent (SES) and a paclitaxel eluting stent (PES). METHODS: The study population consisted of patients with positive or intermediate remodeling and negative remodeling. RESULTS: Sixty-nine patients had positive or intermediate remodeling and 107 patients had negative remodeling. At follow-up, late loss was significantly larger (0.58 +/- 0.65 vs. 0.38 +/- 0.55 mm; p = 0.026) in the patients with positive or intermediate remodeling. The IH volume (22.6 +/- 26.2 vs. 12.4 +/- 17.4 mm(3); p = 0.002) and the percent IH (12.9 +/- 14.8 vs. 7.0 +/- 9.6%; p = 0.002) were significantly higher in the patients with positive or intermediate remodeling. Compared to negative remodeling, the IH volume was higher in the PES patients with positive or intermediate remodeling, but this difference was not noted in the SES patients. Multiple-regression analysis revealed that arterial remodeling was a significant independent variable for predicting IH volume in the PES patients (p = 0.018). A positive correlation was found between the remodeling index and the IH volume in the PES patients (r = 0.234, p = 0.028), but not in the SES patients. CONCLUSIONS: This prospective observational intravascular ultrasound study showed that drug-eluting stents may have a different effect on reducing IH accumulation in lesions with preinterventional positive remodeling characteristics which may be related to the different properties of the drug and delivery platform. PMID- 20588021 TI - Ischemia-modified albumin: is it a reliable diagnostic and prognostic marker for myocardial ischemia in real clinical practice? AB - OBJECTIVES: We investigated whether ischemia-modified albumin (IMA), a novel biomarker of acute myocardial ischemia, is reliable for diagnosing ischemic chest pain and predicting future cardiac events in clinical practice. METHODS: We enrolled 390 patients (age 61.7 +/- 39.9 years) who arrived at the emergency department within 6 h of pain onset. We compared serum IMA levels of patients with ischemic chest pain (ICP) to those with nonischemic chest pain (NICP). RESULTS: NICP was diagnosed in 162 patients and ICP in 205 patients. Median serum IMA levels did not differ between the NICP (99.0 U/ml; 95% confidence interval, 98.2-101.2 U/ml) and the ICP group (99.0 U/ml; 95% confidence interval, 99.4 102.6 U/ml; p = 0.320). During a 2-year follow-up, adverse cardiac events including cardiac death, myocardial infarction and recurrent angina occurred in 25 of 205 patients (12.2%) in the ICP group, but IMA was not predictive of cardiac events. CONCLUSIONS: IMA was neither able to discriminate acute chest pain due to myocardial ischemia from that of other origin nor to predict cardiac events. Therefore, use of serum IMA levels for triage of patients with acute chest pain does not seem effective in clinical practice. PMID- 20588022 TI - Use of ICDAS combined with quantitative light-induced fluorescence as a caries detection method. AB - The purpose of this study was to combine a standardized visually based system, the International Caries Detection and Assessment System (ICDAS), with a sensitive fluorescence-based system, quantitative light-induced fluorescence (QLF), to determine the ability to monitor caries lesion progression. This combination (QLF-I) has the potential to increase the sensitivity of the visual method without compromising specificity. A total of 460 children were enrolled and examined at baseline, 8 months and 12 months by ICDAS and QLF by a single examiner. The examiner repeatability for both methods was comparable, varying between weighted kappa of 0.70 and 0.79. The DMFT score was 6.0 (SD 5.8) at baseline and 6.4 (SD 6.3) at 12 months, and both methods were able to follow the increase in incidence. The QLF-I scored more surfaces at the early ICDAS scores (1 and 2) and score 4. Not all lesions progressed at the same rate, differing by score at baseline and surface type. PMID- 20588023 TI - Preface. PMID- 20588024 TI - MicroRNAs and esophageal squamous cell carcinoma. AB - Esophageal cancer is a common cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is the most predominant type. Certain microRNAs (miRNAs) function in tumorgenesis involved in important biological and pathologic processes. To reveal miRNAs' signatures of ESCC, we analyzed miRNAs extracted from ESCC cell lines with the microRNA microarray. The significant alterations were confirmed by quantitative real-time PCR using miRNAs extracted from cell lines or patients' esophageal biopsy tissues. We found that miR-205 and miR-10a were significantly altered in cellular expression, and might be specific for ESCC with potential roles in the pathogenesis. As a result of function studies in miR 205, alterations in miR-205 expression could modulate the phenotype of epithelial cells towards epithelial-mesenchymal transition characterized by reduced abundance of E-cadherin, that is the ESCC-specific miRNA target and inhibit translationally a representative E-cadherin repressor, ZEB1 and ZEB2. Similarly, miR-10a is reported as a tumor suppressor by controlling cell migration/invasion, as it can target homeobox genes. These results provide insight into the potential mechanisms of ESCC in the pathogenesis. This review also includes a comprehensive overview of the relationship between miRNAs and ESCC. PMID- 20588025 TI - Intranuclear translocation signaling of HB-EGF carboxy-terminal fragment and mucosal defense through cell proliferation and migration in digestive tracts. AB - Mucosal integrity in the digestive tracts is maintained by defense mechanisms which comprise mucin production, microcirculatory blood flow, intercellular junctions, cell growth and mucosal repair. These physiological features are known to be regulated by prostaglandins, nitric oxides, growth factors, and cytokines. Mucosal injury and inflammation occur when cytotoxic attacks overwhelm cellular capacity for defense or repair. Interleukin-8 (IL-8) promotes tumor cell proliferation in colon cancer cells after binding to its receptors, which are members of the G-protein-coupled receptor (GPCR) family. Stimulation of GPCR can induce shedding of epidermal growth factor (EGF) ligands via activation of A disintegrin and metalloprotease (ADAM), with subsequent transactivation of the EGF receptor (EGFR). In parallel with EGF signaling through EGFR activation, heparin-binding (HB)-EGF carboxy-terminal fragment (CTF) signaling is also involved in cell proliferation through nuclear export of promyelocytic leukemia zinc finger. IL-8 induces cell proliferation and migration by an ADAM-dependent intranuclear translocation pathway of HB-EGF-CTF. Here, we focus on the mechanisms of IL-8-induced HB-EGF-CTF signaling, which is involved in cytoprotection and cellular repair. PMID- 20588026 TI - Role of transient receptor potential A1 in gastric nociception. AB - Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. However, little is known about the molecules involved in mechanonociception from the upper gastrointestinal tract. We recently reported that activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase cascade in primary afferent neurons, was induced by noxious gastric distention in the rat, and that the activation of ERK1/2 in dorsal root ganglion (DRG) neurons can be implicated in acute visceral pain. Transient receptor potential (TRP) A1, a member of the TRP family of cation channels, was expressed in both DRG and nodose ganglion (NG) neurons innervating the stomach and in nerve fibers in the gastric wall. TRPA1 was coexpressed with ERK1/2 in gastric primary afferent neurons, and attenuation of TRPA1 activation using antisense peptides and a specific blocker led to suppression of both ERK1/2 activation and visceromotor responses. TRPA1 also significantly colocalized with substance P (SP) and calcitonin gene-related peptide (CGRP) in the thoracolumbar DRG, NG and stomach. These data indicate that SP and CGRP may also be released by TRPA1 activation in primary afferent neurons to elicit neurogenic inflammation and promote visceral hyperalgesia. PMID- 20588027 TI - Characteristics of symptomatic reflux episodes in patients with non-erosive reflux disease who have a positive symptom index on proton pump inhibitor therapy. AB - BACKGROUND AND AIM: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. METHODS: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24 hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. RESULTS: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. CONCLUSIONS: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception. PMID- 20588028 TI - Pathophysiological classification of functional dyspepsia using a novel drinking ultrasonography test. AB - BACKGROUND: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD symptoms includes impaired fundic accommodation, delayed gastric emptying, and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. METHOD: Subjects were 60 successive FD patients according to the Rome III criteria. A drinking-ultrasonography test was performed after subjects had fasted. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. The normal range of cross-sectional area and VAS were set using average +/- standard deviations of 33 healthy volunteers. Cases outside the normal range were diagnosed with a motor or sensory disorder. RESULTS: The drinking-ultrasonography test classified FD patients into four groups without adverse effect or trouble. The distribution of each group was 27% in the normal group, 15% in the impaired relaxation group, 10% in the delayed emptying group, and 48% in the visceral hypersensitivity group. There was no significant correlation between the pathophysiological classification and subtypes of FD defined by the Rome III criteria. CONCLUSION: We developed a novel drinking-ultrasonography test that was effective in classifying FD patients according to pathophysiological features. PMID- 20588029 TI - Prevention of traditional NSAID-induced small intestinal injury: recent preliminary studies using capsule endoscopy. AB - Capsule endoscopy and balloon endoscopy, advanced modalities that now allow for full investigation of the entire small intestine, have revealed that non steroidal anti-inflammatory drugs (NSAIDs) can cause a variety of abnormalities in the small intestine. Traditional NSAIDs can induce small intestinal injuries in over 50% of patients. Several studies have shown that the preventive effect of proton pump inhibitors does not extend to the small intestine, suggesting that concomitant therapy may be required to prevent small intestinal side effects associated with traditional NSAIDs use. Recently, several randomized controlled trials used capsule endoscopy to evaluate the preventive effect of certain drugs on NSAID-induced small intestinal injuries. These studies show that misoprostol and rebamipide have a preventive effect for NSAID-induced small intestinal mucosal injuries. However, these studies included only a small series of healthy volunteers and tested short-term NSAID treatment. Therefore, further extensive studies are clearly required to ascertain the beneficial effect of these drugs. PMID- 20588030 TI - Long-term outcome after double-balloon endoscopy in patients with obscure gastrointestinal bleeding. AB - BACKGROUND AND AIMS: There are limited data concerning the clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) after double-balloon endoscopy (DBE). The aim of the present study was to evaluate the long-term outcome of patients with OGIB after DBE. PATIENTS AND METHODS: Eighty-seven consecutive patients with OGIB (47 men and 40 women; mean age 65.3 years) underwent DBE between July 2006 and December 2009. The criteria for assessment included documented iron deficiency anemia/occult or obscure small intestinal bleeding, and overt small intestinal bleeding. They were followed for a mean period of 41.4 months after DBE, and were divided into two groups according to their outcome, that is a good clinical course group (GC group) and a poor clinical course group (PC group). The clinical characteristics associated with rebleeding after DBE were analyzed by comparison of these two groups. RESULTS: The source of bleeding was identified in 40 patients (46.0%) and endoscopic treatment was required in 21 of them (52.5%). The most frequent source of bleeding was ulcers/erosions (18.4%). During the follow-up period, 39 patients (44.8%) experienced bleeding and/or persistent iron deficiency anemia after DBE, while 48 patients did not. There were no significant differences of clinical characteristics between the two groups. However, there were more patients with diverticular bleeding in the GC group than the PC group, and there were significantly more patients with treatable small intestinal tumors/polyps in the GC group. There were also more patients with normal DBE findings in the GC group. CONCLUSION: This study demonstrated that the rebleeding rate after DBE varies depending on the source of bleeding. PMID- 20588031 TI - Increased expression of DNA methyltransferase-1 in non-neoplastic epithelium helps predict colorectal neoplasia risk in ulcerative colitis. AB - AIMS: To clarify the possible significance of increased expression of DNA methyltransferase (DNMT)-1 in the tumorigenesis of colorectal neoplasia in ulcerative colitis (UC) and to clarify whether analysis of DNMT1 expression in non-neoplastic epithelium can contribute to the prediction of increased risk for UC-associated neoplasia. METHODS: Sixty-two patients with long-standing and extensive UC were included in this study: 31 with colorectal neoplasia (dysplasia in 11 and invasive cancer in 20) and 31 without. Immunohistochemical analysis and quantitative RT-PCR were performed to determine the expression of DNMT1 in rectal epithelium of UC patients without neoplasia, and in non-neoplastic rectal epithelium and colorectal neoplasia of UC patients with neoplasia. RESULTS: The immunoreactive DNMT1 expression gradually increased from rectal epithelium of UC patients without neoplasia (0.13 +/- 0.07) to non-neoplastic rectal epithelium of UC patients with neoplasia (0.32 +/- 0.12, p < 0.001), and to colorectal neoplasia (0.54 +/- 0.20, p < 0.001). Among 31 neoplasias, there was no difference in the immunoreactive DNMT1 expressions between dysplasia and invasive cancer (0.47 +/- 0.52 vs. 0.58 +/- 0.63). The expression level of DNMT1 mRNA tended to increase gradually from rectal epithelium of UC patients without neoplasia (0.53 +/- 0.34) to non-neoplastic rectal epithelium of UC patients with neoplasia (0.88 +/- 0.57, p = 0.06), and to colorectal neoplasia (1.38 +/- 0.64, p = 0.07). CONCLUSION: Increased expression of DNMT1 in non-neoplastic epithelium may precede or be a relatively early event in UC-associated tumorigenesis, and may help predict the risk of colorectal neoplasia in UC. PMID- 20588032 TI - Molecular diagnosis and translymphatic chemotherapy targeting sentinel lymph nodes of patients with early gastrointestinal cancers. AB - The sentinel lymph node (SLN) is defined as the lymph node(s) that first receives lymphatic drainage from the site of the primary tumor. Recent progress in molecular techniques has demonstrated the presence of micrometastatic tumor cells in SLNs. Quantitative real-time RT-PCR assay, which enables rapid analysis, is currently being undertaken for intraoperative molecular diagnosis of SLNs. We developed an intraoperative real-time RT-PCR assay to detect micrometastasis in SLNs for early gastric cancer. All SLNs and randomly selected non-SLNs in 96 cT1 or cT2 gastric cancer patients were biopsied intraoperatively and examined by routine hematoxylin and eosin staining, immunohistochemistry with anticytokeratin antibody (AE1/AE3), and multimarker real-time RT-PCR assay including cytokeratin (CK) 19, CK20, and carcinoembryonic antigen. All patients with histopathologically verified metastasis in their SLNs demonstrated positive results by RT-PCR assay. Forty percent of patients with histopathologically negative SLNs showed positive SLNs by RT-PCR assay. RT-PCR assay revealed that 4 patients (4%) with negative SLNs had positive non-SLNs; however, these positive non-SLNs were identified within each SLN basin. We recently developed a new drug delivery system targeting SLNs with a phospholipid polymer, using 2 methacryloyloxyethyl phosphorylcholine conjugated with paclitaxel. Our preliminary data suggest that this novel drug delivery system may be feasible for translymphatic chemotherapy targeting SLNs of patients with cN0 early gastrointestinal cancer, who have the potential for occult metastasis in SLNs. Endoscopic resection of the primary tumor followed by translymphatic chemotherapy targeting SLNs may become a promising minimally invasive multidisciplinary therapy. PMID- 20588033 TI - Challenges in staging systems for colorectal cancer: clinical significance of metastatic lymph node number in colorectal cancer and mesorectal extension in rectal cancer. AB - In many countries, treatment for cancer is performed based on staging systems in which the degree of cancer development is defined objectively. A common staging system is thus needed to compare outcomes. The staging system for colorectal cancer in Japan has been made to enhance consistency with the TNM classification, and the categorization of metastatic lymph nodes and depth of invasion have been revised in recent years. Although these are important factors that determine disease stage, relationships between each factor and recurrence have shown differing prognoses. In our retrospective study, the prognosis of a group with only one metastatic lymph node was significantly better compared to a group with > or = 2 metastatic lymph nodes. In addition, rectal cancer with mesorectal extension >5 mm showed low relapse-free survival rates and high recurrence rates. The validity of staging systems should thus be inspected from various perspectives. PMID- 20588034 TI - Psychosocial factors, psychiatric illness and functional gastrointestinal disorders: a historical perspective. AB - A new classification of functional gastrointestinal disorders (FGID) became available recently, based on consensus in expert committees ('Rome III process'). It is widely accepted that these frequent disorders, although their pathophysiology remains incompletely understood, result from a complex reciprocal interaction between biological, psychological and social factors that can be predisposing, precipitating and/or perpetuating. Comorbidity with psychiatric disorders, especially mood and anxiety disorders, is high. Modern epidemiologic, psychophysiological and functional neuroimaging studies have partially elucidated the mechanisms underlying the relation between cognitive-affective processes on the one hand and GI function and symptom reporting on the other. The aim of this article is to provide a noncomprehensive historical review of the literature on FGID up to the mid-20th century, with special emphasis on the role of psychosocial factors and psychiatric comorbidity. We can conclude from this review that a lot of the knowledge that became available recently through modern research methodology can also be found in the historical psychosomatic and neuroscience literature, though obviously less empirically grounded. This provides further support for an integrative, multidisciplinary biopsychosocial approach to FGID. PMID- 20588035 TI - In spite of good results with 'inject and cut', should we scrutinize it? - yes, we should! PMID- 20588036 TI - Efficacy, safety and outcomes of 'inject and cut' endoscopic mucosal resection for large sessile and flat colorectal polyps. AB - BACKGROUND AND STUDY AIMS: The study examines the outcomes of the 'inject and cut' endoscopic mucosal resection (EMR), for large sessile and flat colorectal polyps. PATIENTS AND METHODS: Between January 2006 and December 2008 all patients referred to our institution for EMR of large polyps were prospectively evaluated. The accuracy of lifting sign and the rate of en bloc and piecemeal resection, complications and recurrence were analyzed. RESULTS: A total of 157 patients with 182 lesions (median size 24.7 +/- 10.2 mm) were included in the study. The most frequent location was the sigmoid colon in 30.2%. Because of non-lifting sign, 5/182 lesions were referred to surgical resection and 177 (43 flat and 134 sessile) were resected, 79 (44.6%) en bloc and 98 (55.4%) piecemeal. There were 20 procedural (11.3%) and 2 late (1.1%) bleeding, 4 post-polypectomy syndrome (2.2%) and 2 perforations (1.1%). Bleeding was related to malignancy (p = 0.01). Intramucosal cancer was observed in 5 cases (2.8%) while invasive cancer was seen in 8 (4.5%). Malignancy was related to polyp size >or=30 mm (p = 0.002). Follow up colonoscopy was performed in 147 patients with 172 EMR for a mean of 19.8 months. Recurrence was observed in 12/172 (6.9%) polyps. CONCLUSION: Inject and cut EMR is practical and effective with a low risk of complication and local recurrence. PMID- 20588037 TI - Impact of gluten withdrawal on health-related quality of life in celiac subjects: an observational case-control study. AB - AIMS: To evaluate health-related quality of life (HRQoL) in celiac disease (CD) patients at the time of diagnosis and during a gluten-free diet (GFD). PATIENTS AND METHODS: We enrolled 43 adult CD patients (18 with a typical and 15 with an atypical clinical presentation, and 10 with dermatitis herpetiformis, DH) and 86 age- and sex-matched healthy controls. We administered the Short Form 36 Health Survey (SF-36) questionnaire at diagnosis and after 1, 12 and 24 months of a GFD. RESULTS: At the time of diagnosis CD patients showed significantly lower SF-36 scores than controls; this figure was observed in women but not in men. At baseline, both typical and atypical CD patients had lower SF-36 scores than controls, while DH patients showed a SF-36 profile comparable to that of controls. During a GFD the SF-36 scores improved continuously in CD patients and in the female subgroup, becoming similar to those of matched controls at 1-year follow-up. After gluten withdrawal typical and atypical CD patients improved their SF-36 scores and reached values comparable to those of controls. CONCLUSIONS: At diagnosis, CD patients perceived a poor HRQoL; this figure appears to be mostly associated with female gender. In all subgroups of CD patients with a low HRQoL at diagnosis, the GFD allowed progressive restoration of HRQoL perception. PMID- 20588038 TI - Acute complications of Crohn's disease: comparison of multidetector-row computed tomographic enterography with magnetic resonance enterography. AB - OBJECTIVE: To compare multidetector-row computed tomographic (MDCT) enterography with magnetic resonance (MR) enterography performed upon acute exacerbation of Crohn's disease. SUBJECTS AND METHODS: Fifty-seven patients (mean age 33.5) with proven Crohn's disease and symptoms suggesting acute exacerbation were prospectively included. After oral administration of 1-2 liters of 5% methylcellulose, MDCT and MR enterography were performed on each patient (mean delay <24 h). Three radiologists blindly and independently evaluated each examination for technical quality and in terms of 8 pathological features of Crohn's disease. Observers' agreement, sensitivity and specificity resulted from comparison with the reference standard [surgery (n = 24), endoscopy (n = 17) and long-term follow-up (n = 16)]. RESULTS: MDCT enterography demonstrated fewer artifacts than MR enterography (p < 0.0001). In 48 MDCT/MR enterography examinations, active disease was demonstrated: abscesses (n = 11), fistulas (n = 13), stenoses (n = 23) and/or intestinal inflammation (n = 38). Observers' agreement (range 0.56-0.87) was not significantly different between MDCT and MR enterography, neither in terms of sensitivity (range 58-95%) nor specificity (range 67-100%) for each of the 8 pathological features. CONCLUSION: Statistically, MR enterography is of similar diagnostic value as MDCT enterography for acute complications of Crohn's disease. Since the typical Crohn's disease patient is young and will very likely undergo life-long imaging, and given concerns about radiation exposure with MDCT, MR enterography should be the preferred modality. PMID- 20588039 TI - Appropriateness of Crohn's disease therapy in gastroenterological rehabilitation. AB - BACKGROUND/AIMS: The treatment criteria developed by the European Panel on the Appropriateness of Crohn's Disease (CD) Therapy (EPACT) have not been applied to rehabilitation. Thus, we retrospectively evaluated appropriateness of treatments during CD rehabilitation using the EPACT website. METHODS: We included our 1-year inpatient rehabilitation patients that had been assigned the International Classification of Disease Code for CD. The appropriateness of treatment was assessed in CD categories exhibiting frequent treatment changes. Treatment plans were compared to EPACT recommendations. RESULTS: Charts of 337 proven CD patients (median age 42 [range 17-65] years, 250 women, median Crohn's Disease Activity Index 140 [range -3 to 427] units) were assigned to EPACT categories. The categories 'steroid-dependent' and 'steroid-refractory' exhibited frequent treatment changes. In these 59 patients, 16 treatments (13 azathioprine, 1 methotrexate, 2 infliximab) were rated as appropriate. One certolizumab treatment was uncertain. 22 treatments with azathioprine were inappropriate (21 due to underdosing), and 93 treatments (30 mesalamine, 59 steroid, 4 budesonide) were not rated. The number of differences between treatment plans and EPACT recommendations decreased from 45 to 25 in both CD categories (p < 0.0001). CONCLUSIONS: We introduce the EPACT website as a practical advance towards an optimal therapy in rehabilitants with steroid-dependent or -refractory CD. PMID- 20588040 TI - Expression of a hypoxia-associated protein, carbonic anhydrase-9, correlates with malignant phenotypes of gastric carcinoma. AB - BACKGROUND/AIMS: Gastric cancers are characterized by a heterogeneously hypoxic environment. Hypoxia might stimulate the malignant potential of cancer cells. The purpose of our study was to clarify the significance of hypoxia in gastric carcinoma by evaluating the expression of a hypoxic marker, namely carbonic anhydrase-9 (CA-9). METHODS: A total of 265 patients who had undergone a resection of the primary tumor and were confirmed histologically to have sporadic gastric cancer were enrolled in this study. We evaluated the immunohistochemical expression of CA-9 in the paraffin-embedded specimens of 265 gastric adenocarcinomas. RESULTS: The CA-9 expression was positive in 88 (33%) of 265 gastric carcinomas. The CA-9 expression level was significantly high in cases of type 4 carcinoma (60%, p < 0.001) and diffuse type carcinoma (41%, p < 0.001), and significantly correlated with the invasion depth (p < 0.001), lymph node metastasis (p < 0.001) and lymphatic invasion p = 0.002). The prognosis for CA-9 positive patients was significantly poorer than that of CA-9-negative patients (p = 0.003, log-rank). CONCLUSION: Hypoxia might be associated with aggressive tumor phenotypes of gastric carcinomas. The hypoxic marker CA-9 may be a useful prognostic indicator. PMID- 20588041 TI - Colonic adenomas found via colonoscopy: yield and risk factors for high-grade dysplasia. AB - BACKGROUND AND AIMS: The adenoma-carcinoma sequence is the model for colorectal carcinoma (CRC) developing through high-grade dysplasia (HGD) to CRC. The aim was to assess prevalence and location of adenomas found during colonoscopy and risk factors for HGD. MATERIAL AND METHODS: A population-based study using all colonoscopies and polyp specimens registered between 2000 and 2004 in Iceland. Multiple logistic regression analysis was used to assess independent risk factors for HGD. RESULTS: A total of 3,315 adenomas were removed from 2,385 patients. Only 14.0% were >1 cm in size. HGD was found in 135 (4.1%) of the adenomas and tubulovillous/villous histology in 15.0%. The prevalence of adenomas in the 50- to 69-year age group was 15.5%, and 21.5% in the >or=70-year group. 60.9% of them were located distal to the splenic flexure. Independent risk factors for HGD were in the order of importance: size; multiplicity; tubulovillous/villous histology; location in rectum, and age. The prevalence of HGD in the group with an adenoma size of 0.6-1.0 cm was 4.1% and in the 40- to 69-year age group it was 3.7%. CONCLUSION: The study suggests a potential 15% yield per colonoscopy of adenomas in 50- to 69-year-olds. There is an appreciable risk of HGD in diminutive polyps and in middle age. PMID- 20588042 TI - Ileocolonic findings in Behcet's disease. PMID- 20588043 TI - Recurrent sigmoid volvulus treated by colonoscopic reduction. PMID- 20588044 TI - Ulcerative colitis with Takayasu disease. PMID- 20588045 TI - Glycochenodeoxycholate-induced apoptosis is not reduced by augmenter of liver regeneration in the human hepatoma cell line HuH-7. PMID- 20588046 TI - Did Jean-Martin Charcot contribute to stroke? AB - Stroke was never identified as a significant, autonomous field of activity of the emerging school of neurology at La Salpetriere, which developed after the appointment of Jean-Martin Charcot (1825-1893) during the last days of 1861. However, stroke was already present in Charcot's first paper (1851), which dealt with a case of multiple organ cardiac embolism, including middle cerebral artery infarction, at a time when the studies of Rudolf Virchow on thromboembolism were unknown in France. A few years later, Charcot made a still up-to-date description of vascular intermittent claudication, which had only been reported in the horse. In the 1860s, Charcot and his pupils presented several major works dealing with cerebrovascular disease, including famous studies on miliary aneurysms in cerebral hemorrhage. This work was done with Charles Bouchard, at the time Charcot's 'interne', but who would become one of his 'political' opponents 2 decades later, when in 1892, as president of the 'agregation' jury, he rejected the professorship application of 4 proteges of Charcot, including Joseph Babinski and Georges Gilles de la Tourette. Further work on cerebrovascular disease by Charcot included histological studies of brain 'softening', paraneoplastic cerebral arterial occlusion and consequences of stroke (e.g. arthropathies, vegetative changes, contractures and abnormal movements). Brain localization, one of Charcot's major neurological topics, was also largely based on stroke case studies. Charcot's work on stroke remains poorly recognized, but it demonstrates his unique skills in stimulating scientific work in younger colleagues, many of whom subsequently became major figures of neurology and psychiatry. PMID- 20588047 TI - Predictive genetic tests in neurodegenerative disorders: a methodological approach integrating psychological counseling for at-risk individuals and referring clinicians. AB - The identification of the molecular basis of numerous hereditary neurological disorders allowed the feasibility of predictive genetic tests for at-risk family members. In agreement with international guidelines, we tested a protocol for a predictive test to optimize cooperation among specialists, well-being of participants, and organization of clinical activities. The psychiatrist/psychologist did not meet the at-risk subjects, but cooperated with the team, integrating psychological support for participants and clinicians. We enrolled 60 subjects at risk for Huntington disease, and 32 at risk for spinocerebellar ataxias. Seventy-two subjects (78%) continued the visit program; 55 (60%) received the genetic result, and 38 subjects (41%) completed the program. Participation and outcome were similar in both groups. Mean psychological scores were all below significant levels; however, the need for psychological support was recognized for 5 mutation carriers and a non-carrier. Our data provide a methodological example of a simple and safe procedure for a predictive test, and indicate that the clinical conference represents a good setting to handle psychosocial impact associated with disclosure of genetic results in hereditary late-onset disorders. PMID- 20588048 TI - Functional histology of the macula flava in the human vocal fold--Part 2: Its role in the growth and development of the vocal fold. AB - OBJECTIVE: This study aims to clarify the role of the maculae flavae (MFe) during growth and development of the human vocal fold mucosa (VFM). METHODS: Our current results concerning the MFe in the human newborn, infant, and child VFM are summarized. RESULTS: Newborns already had immature MFe at the same sites as adults. They were composed of dense masses of vocal fold stellate cells (VFSCs), whereas extracellular matrix components were sparse. VFSCs in the newborn MFe had already started synthesizing extracellular matrices (EM). During infancy, the EM synthesized in the MFe appeared in the VFM to initiate the formation of the three dimensional extracellular matrix structure of the human VFM. During childhood, MFe including VFSCs continued to synthesize EM such as collagenous, reticular, and elastic fibers, and hyaluronic acid (glycosaminoglycan), which are essential for the human VFM as a vibrating tissue. The MFe in newborns, infants and children were related to the growth and development of the human VFM. CONCLUSION: Human MFe including VFSCs were inferred to be involved in the metabolism of EM, essential for the viscoelasticity of the human VFM, and are considered to be an important structure in the growth and development of the human VFM. PMID- 20588049 TI - Prospective evaluation of the outcome of velopharyngeal insufficiency therapy after simultaneous double z-plasty and sphincter pharyngoplasty. AB - OBJECTIVE: One of the main goals in the management of cleft palate is to achieve a good quality of speech. The aim of the prospective study was to evaluate the effectiveness of therapy in patients with velopharyngeal insufficiency treated by simultaneously performed Furlow and Orticochea operations. PATIENTS AND METHODS: From May 2007 to May 2008 we treated 14 consecutive patients (6 males and 8 females, mean age 14 years). The indications for surgery were based on nasofiberscopic examination, evaluation of speech quality, nasometry and morphology of the palate. The velopharyngeal closure was below 80% in all the patients; they had pronounced nasality and limited intelligibility of speech. All the palates were short. RESULTS: The final outcome of treatment was based on the combined evaluation of 4 parameters: closure, speech intelligibility, nasality and the nasalance index. Ten patients achieved full recovery (71%), the remaining 4 had improved recovery (29%). CONCLUSION: A 1-stage Furlow operation and sphincter pharyngoplasty are an effective modality in the therapy of velopharyngeal insufficiency. Indications for posterior pharyngeal flap pharyngoplasty should be limited to the cases in which a simultaneous Furlow operation and sphincter pharyngoplasty are not possible due to a deficit of the palatine tissue. PMID- 20588050 TI - Professional opera tenors' vocal tract configurations in registers. AB - OBJECTIVE: Tenor singers may reach their top pitch range either by shifting from modal to falsetto register or by using their so-called 'voix mixte'. MATERIAL AND METHODS: In this study, dynamic real-time MRI of 8 frames per second was used to analyze the vocal tract profile in 10 professional opera tenors, who sang an ascending scale from C4 (262 Hz) to A4 (440 Hz) on the vowel /a/. The scale included their register transition and the singers applied both register techniques in different takes. RESULTS: Modal to falsetto register changes were associated with only minor vocal tract modifications, including elevation and tilting of the larynx and a lifted tongue dorsum. Transitions to voix mixte, by contrast, were associated with major vocal tract modifications. Under these conditions, the subjects widened their pharynges, their lip and jaw openings, and increased their jaw protrusion. These modifications were stronger in more 'heavy' tenors than in more 'light' tenors. The acoustic consequences of these articulatory changes are discussed. PMID- 20588051 TI - Effects of the Voice over Internet Protocol on perturbation analysis of normal and pathological phonation. AB - OBJECTIVE: In this study, a Voice over Internet Protocol (VoIP) communication based on G.729 protocol was simulated to determine the effects of this system on acoustic perturbation parameters of normal and pathological voice signals. PATIENTS AND METHODS: Fifty recordings of normal voice and 48 recordings of pathological voice affected by laryngeal paralysis were transmitted through a VoIP communication system. The acoustic analysis programs of CSpeech and MDVP were used to determine the percent jitter and percent shimmer from the voice samples before and after VoIP transmission. The effects of three frequently used audio compression protocols (MP3, WMA, and FLAC) on the perturbation measures were also studied. RESULTS: It was found that VoIP transmission disrupts the waveform and increases the percent jitter and percent shimmer of voice samples. However, after VoIP transmission, significant discrimination between normal and pathological voices affected by laryngeal paralysis was still possible. It was found that the lossless compression method FLAC does not exert any influence on the perturbation measures. The lossy compression methods MP3 and WMA increase percent jitter and percent shimmer values. CONCLUSION: This study validates the feasibility of these transmission and compression protocols in developing remote voice signal data collection and assessment systems. PMID- 20588052 TI - Breath group analysis for reading and spontaneous speech in healthy adults. AB - AIMS: The breath group can serve as a functional unit to define temporal and fundamental frequency (f0) features in continuous speech. These features of the breath group are determined by the physiologic, linguistic, and cognitive demands of communication. Reading and spontaneous speech are two speaking tasks that vary in these demands and are commonly used to evaluate speech performance for research and clinical applications. The purpose of this study is to examine differences between reading and spontaneous speech in the temporal and f0 aspects of their breath groups. METHODS: Sixteen participants read two passages and answered six questions while wearing a circumferentially vented mask connected to a pneumotach. The aerodynamic signal was used to identify inspiratory locations. The audio signal was used to analyze task differences in breath group structure, including temporal and f0 components. RESULTS: The main findings were that spontaneous speech task exhibited significantly more grammatically inappropriate breath group locations and longer breath group duration than did the passage reading task. CONCLUSION: The task differences in the percentage of grammatically inadequate breath group locations and in breath group duration for healthy adult speakers partly explain the differences in cognitive-linguistic load between the passage reading and spontaneous speech. PMID- 20588054 TI - Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid. AB - BACKGROUND/AIMS: Vitamin C transporter proteins SVCT1 and SVCT2 are required for the absorption and transport of vitamin C in humans. This study aims to determine whether common SVCT genotypes modify the association between dietary vitamin C and serum ascorbic acid. METHODS: Non-smoking men and women (n=1,046) aged 20-29 were participants of the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for two SVCT1 (rs4257763 and rs6596473) and two SVCT2 (rs6139591 and rs2681116) polymorphisms. RESULTS: No diet-gene interactions were observed for the vitamin C transporter polymorphisms, however, the average (mean+/-SE) serum ascorbic acid concentrations differed between rs4257763 genotypes (GG: 24.4+/-1.3, GA: 26.8+/-1.1, AA: 29.7+/-1.4 micromol/l; p=0.002). For this polymorphism, the correlation between dietary vitamin C and serum ascorbic acid was only significant in subjects with a G allele. The SVCT2 polymorphisms also appeared to modify the strength of the diet-serum correlation. CONCLUSIONS: Our findings demonstrate that genetic variation in SVCT1 can influence serum ascorbic acid concentrations and that SVCT1 and SVCT2 genotypes modify the strength of the correlation between dietary vitamin C and serum ascorbic acid. PMID- 20588053 TI - An 8-week high-fat diet induces obesity and insulin resistance with small changes in the muscle transcriptome of C57BL/6J mice. AB - BACKGROUND: Skeletal muscle is responsible for most of the insulin-stimulated glucose uptake and metabolism. Therefore, it plays an important role in the development of insulin resistance, one of the characteristics of the metabolic syndrome (MS). As the prevalence of the MS is increasing, there is an urgent need for more effective intervention strategies. METHODS: C57BL/6J mice were fed an 8 week low-fat diet (10 kcal%; LFD) or high-fat diet (45 kcal%; HFD). Microarray analysis was performed by using two comparisons: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. RESULTS: Although an 8-week HFD induced obesity and impaired insulin sensitivity, HFD-responsive changes in the muscle transcriptome were relatively small (<1.3-fold). In fact, 8-weeks of aging induced more pronounced changes than an HFD. One comparison revealed the transcriptional downregulation of the mito- gen-activated protein kinase cascade, whereas both comparisons showed the upregulation of fatty acid oxidation, demonstrating that the two comparison strategies are confirmative as well as complementary. CONCLUSION: We suggest using complementary analysis strategies in the genome-wide search for gene expression changes induced by mild interventions, such as an HFD. PMID- 20588055 TI - Knockdown of Cyclophilin D Gene by RNAi Protects Rat from Ischemia/ Reperfusion Induced Renal Injury. AB - BACKGROUND/AIMS: Mitochondrial permeability transition has a critical role in ischemia/reperfusion (I/R)-induced kidney injury. It is thought that mitochondrial permeability transition occurs after the opening of the permeability transition pore, a channel which putatively consists of a voltage dependent anion channel, adenine nucleotide translocator and cyclophilin D (CypD). Much evidence shows that CypD plays an important role in I/R-induced injury. METHODS: To evaluate the role of CypD following I/R renal injury, we tested the hypothesis that knockdown of CypD gene by RNA interference (RNAi) protects rat from I/R-induced renal injury. RESULTS: Our data show that knockdown of CypD by RNAi protects normal rat kidney cell line from hypoxia-induced necrotic death. Infection of lentivirus expressing CypD RNAi sequence produces a significant reduction of CypD at both mRNA and protein levels. Both pathologic and biochemical analyses show that knockdown of CypD by RNAi protects rat kidney from I/R-induced renal injury. CONCLUSION: Our study provides the evidence that CypD may be a potential target for protecting I/R-induced renal injury. PMID- 20588056 TI - Angiotensin II Type 1 Receptor Antagonism Attenuates Abnormalities in Dynamic Renal Blood Flow Autoregulation in Rats with Endotoxin-Induced Acute Kidney Injury. AB - BACKGROUND: The aim was to examine the role of angiotensin II type 1 receptors in dynamic autoregulation of renal blood flow (RBF) in endotoxemia. METHODS: Experiments were performed on anesthetized rats 16 h after intraperitoneal lipopolysaccharide (LPS) or vehicle administration. After baseline measurements, groups Sham-Saline, LPS-Saline and LPS-Candesartan received isotonic saline or candesartan (10 MUg kg(-1) i.v.). Data were collected during eight consecutive 20 min clearance periods (C1-8). Transfer function (TF) analysis in the frequency domain was used to examine dynamic autoregulation of RBF. RESULTS: Endotoxemic rats showed an approximate 50% reduction in glomerular filtration rate (GFR) and RBF (p < 0.05 vs. Sham-Saline). Candesartan significantly increased RBF (+40 +/- 6% vs. baseline; p < 0.05) but did not significantly influence GFR. Endotoxemic animals showed a normal myogenic response but had elevated TF gain values in the frequency range of the tubuloglomerular feedback mechanism (TGF; 0.01-0.03 Hz) reflecting impaired autoregulation (periods C3-4, 2.2 +/- 1.6 vs. -2.6 +/- 0.6 dB, p < 0.05, and C7-8, -0.4 +/- 1.3 vs. -4.0 +/- 0.8 dB, p < 0.05; in groups LPS Saline and Sham-Saline, respectively). Candesartan normalized TF gain in this frequency range (periods C7-8, -6.1 +/- 2.3 dB in group LPS-Candesartan, p < 0.05 vs. LPS-Saline). CONCLUSION: Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF. PMID- 20588057 TI - Correlation between the Indexes of Insulin Resistance and Renal Function in the Presence of Hypertension. AB - BACKGROUND/AIMS: It is important to establishthe association between insulin resistance and renal function; however, the reported associations differ across studies. Different underlying pathophysiologies of the studied populations may affect the associations. There have been no reports on the relationship between insulin resistance and renal function in the presence of hypertension (HT). We investigated the correlation between a homeostasis model assessment of insulin resistance (HOMA-IR) and the estimated glomerular filtration rate (eGFR) in subjects with and without HT. METHODS: The study included 214 individuals (mean age: 65.6 years) who were nonmedicated and cardiovascular disease-free. Clinical variables, including blood pressure (BP), creatinine, glucose and lipid panels, were measured. RESULTS: The HT group showed significantly higher levels of systolic/diastolic BP than the non-HT group. A multiple linear regression analysis revealed that the eGFR in the non-HT group was independently, significantly and inversely correlated with HOMA-IR, while the eGFR in the HT group was independently, significantly and inversely correlated with systolic BP, but not with HOMA-IR. CONCLUSIONS: A clearer correlation between HOMA-IR and eGFR was observed in the non-HT group than the HT group, suggesting that HT may attenuate the direct correlation between the insulin resistance and renal function indices. PMID- 20588058 TI - Renoprotective Effects of Various Angiotensin II Receptor Blockers in Patients with Early-Stage Diabetic Nephropathy. AB - BACKGROUND: There is increasing evidence that inhibition of the renin-angiotensin system provides renoprotection independent of blood pressure lowering. The aim of the present study was to determine whether various angiotensin II receptor blockers (ARBs) affect urinary albumin excretion (UAE), urinary liver-type fatty acid-binding protein (L-FABP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in early-stage diabetic nephropathy patients with microalbuminuria. METHODS: Sixty eight diabetic nephropathy patients with microalbuminuria were randomly allocated to 1 of 4 treatment groups: losartan 100 mg/day (group A), candesartan 12 mg/day (group B), olmesartan 40 mg/day (group C), or telmisartan 80 mg/day (group D). Treatment was continued for 12 months. UAE, L-FABP and 8-OHdG excretion, serum creatinine, and 24-hour creatinine clearance (Ccr) were measured. RESULTS: The serum creatinine and 24-hour Ccr were not affected during the experimental period in any of the groups. Systolic and diastolic blood pressures, UAE, urinary L-FABP and 8-OHdG excretion were significantly reduced after 6 and 12 months compared with baseline in any of the groups. DeltaL-FABP and Delta8-OHdG were significantly greater in group D than in the other 3 groups after 12 months. CONCLUSIONS: ARBs have renoprotection and this effect of telmisartan appears to be more potent than that of losartan, candesartan, or olmesartan in early-stage diabetic nephropathy patients. PMID- 20588059 TI - Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH1-34): A Pilot Study. AB - BACKGROUND: Adynamic bone disease (ABD) is caused by a relative or absolute parathyroid hormone (PTH) deficiency. Teriparatide (PTH1-34) is an osteoanabolic agent in clinical use. Here, it was hypothesized that treatment with teriparatide improves bone mineral density (BMD) of ABD patients. PATIENTS AND METHODS: Seven hemodialysis patients with ABD and a median iPTH level of 22 pg/ml were evaluated in this open-label, prospective, 6-month observational pilot-study. All patients received 20 MUg teriparatide/day subcutaneously. Serologic bone markers, BMD and coronary artery calcification (CAC) were measured at baseline and after 6 months. RESULTS: Teriparatide therapy led to a significant increase in lumbar spine (0.885 +/- 0.08 vs. 0.914 +/- 0.09 g/cm(2), p < 0.02), but not femoral neck (0.666 +/- 0.170 vs. 0.710 +/- 0.189 g/cm(2), p = 0.18) BMD. Compared to pretreatment values, calculated monthly changes in BMD improved significantly in both the lumbar spine and femoral neck (p < 0.02). Changes in serologic markers of bone turnover and CAC scores were not statistically significant. CONCLUSION: Teriparatide therapy might improve low BMD in hemodialysis patients with ABD. Further clinical studies are needed to establish teriparatide as a therapeutic option for dialysis patients with ABD. PMID- 20588060 TI - Gender-related determinants of advanced subclinical atherosclerosis in patients undergoing kidney transplantation. AB - BACKGROUND: Cardiovascular disease caused by atherosclerosis remains a major cause of morbidity and mortality in patients with end-stage renal disease (ESRD). We evaluated the potential association of cardiovascular risk factors including asymmetric dimethyl L-arginine (ADMA) and the soluble receptor for advanced glycation end products (sRAGE) with preclinical atherosclerosis in patients undergoing kidney transplantation. PATIENTS AND METHODS: In 92 males and 47 females undergoing the first cadaveric renal transplantation, ADMA, sRAGE and common risk factors including lipid parameters were evaluated as potential predictors of preclinical atherosclerosis defined as the Belcaro score (focused on advanced atherosclerotic changes) measured by ultrasound. RESULTS: The prevalence of atherosclerotic changes was approximately 70% in men and women. In logistic regression, age, history of smoking, presence of diabetes mellitus, and plasma triglycerides were the strongest independent predictors for advanced atherosclerosis in the whole group. In unadjusted analyses advanced atherosclerosis was also associated with sRAGE in men and with the atherogenic index of plasma in women. CONCLUSION: Apart from traditional cardiovascular risk factors, plasma triglycerides were found to be strong and independent predictors of advanced atherosclerosis in patients with ESRD. In addition, sRAGE was associated with atherosclerosis in men and the atherogenic index of plasma in women. PMID- 20588061 TI - Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF KB in a model of membranous glomerulonephritis. AB - BACKGROUND/AIMS: Passive Heymann nephritis (PHN) is a model of human membranous glomerulonephritis characterized by heavy proteinuria. We have recently demonstrated activation of NF-kappaB by podocytes in this model. In this study, therefore, we have determined whether dexamethasone (DEX) and pyrrolidine dithiocarbamate (PDTC), therapies that inhibit NF-kappaB, influence proteinuria. METHODS: Twenty-one days after induction of PHN, rats were divided into three groups: group 1 received saline, group 2 received DEX for 7 days, and group 3 received PDTC for 7 days. The effects of these drugs on activation of NF-kappaB and proteinuria were then determined. RESULTS: DEX administration was associated with a very significant increase in proteinuria, whereas PDTC produced a slight decrease. Within the glomerulus, both agents were associated with increased levels of IL-1beta mRNA and protein, compared with untreated rats, and there was increased nuclear localization of p50 in both of the treated groups. Neither agent, therefore, inhibited NF-kappaB activation within the glomerulus. Both agents produced a decrease in the systemic anti-sheep Ig immune response, and there was reduced interstitial alphabeta T-cell infiltration compared with controls. CONCLUSION: These data suggest that agents predicted to inhibit NF kappaB might have opposing effects in membranous glomerulonephritis. The use of steroids to treat membranous glomerulonephritis, therefore, might produce unpredictable results, depending on whether suppression of the systemic immune response or inflammatory events within the kidney is more important in a particular patient. PMID- 20588062 TI - Myeloma light chain-induced renal injury in mice. AB - We investigated the effects of human light chain (LC) protein-overload in mice kidney to gain further insights into the molecular mechanisms involved in the pathogenesis of myeloma kidney. Intact male C57BL/6, 10- to 12-week-old mice were given daily intraperitoneal (i.p.) injections of 1 ml of human kappa-LCs (1.5 mg/ml, low dose), or (100 mg/ml, high dose) to uninephrectomized mice for 2 weeks. Intact, sham-operated or uninephrectomized control animals were given the same volume (1 ml/day) of saline, human serum albumin (10 mg/ml) or bovine serum albumin (100 mg/ml) i.p. for 2 weeks in place of LCs. The low-dose LC-treated mice had human LCs in their urine and a significant increase in monocyte chemoattractant protein-1 (MCP-1) mRNA in the kidneys. Uninephrectomized mice treated with high-dose kappa-LCs showed tubule casts, and foci of intracytoplasmic rhomboid crystals within the proximal tubules, along with cytoskeletal disruptions and alterations in the brush-border membrane, and high concentrations of human kappa-LC were present in their sera. High-dose LC treatment also led to increases in serum creatinine and tumor necrosis factor alpha levels, and marked increases in interleukin-6 and MCP-1 expression as well as cellular apoptosis in the kidneys. These studies demonstrate that myeloma LC overload over a range of LC concentrations in mice causes significant functional and morphological kidney injury. The model should be helpful in investigating pathophysiologic mechanisms and exploring therapeutic interventions for myeloma kidney and other LC-associated renal disorders. PMID- 20588063 TI - Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis. AB - BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, alpha-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but alpha-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas alpha-actinin was unchanged. PMID- 20588064 TI - Spectroscopic noninvasive measurement of hemoglobin compared with capillary and venous values in neonates. AB - BACKGROUND: Venepuncture-related blood loss is a common cause of neonatal anemia. Currently, this is the only way to obtain hemoglobin levels. This causes distress for the infant but can also lead to the need for blood transfusions. Recently, a new technique for measuring hemoglobin levels non-invasively has been developed to reduce iatrogenic blood loss and pain. OBJECTIVE: To compare hemoglobin levels obtained using a transcutaneous spectroscopic device (Mediscan 2000, MBR Optical Systems, Wuppertal, Germany) with venous or capillary blood samples in neonates. METHODS: Single-center prospective cohort study of term and preterm infants. The white light spectroscopic device was placed on the forearm for 60 s to measure hemoglobin content within 4 h of venous or capillary blood sampling. Pain reactions of the infants were assessed by using a neonatal pain assessment tool. Results were analyzed by Bland-Altman comparison and Wilcoxon signed-rank test. RESULTS: 80 infants (mean gestational age 29.8 +/- 3.8 weeks, mean birth weight 1,300 +/- 690 g) were enrolled into the study. A total of 313 spectroscopic recordings within 2 h of a clinically indicated blood sample (181 capillary, 142 venous) were taken. The correlation coefficient R(2) was 0.96 for capillary/spectroscopic and 0.99 for venous/spectroscopic pairs. Pain scores were significantly less for the spectroscopic measurements (p < 0.01). CONCLUSION: The results show good correlation between the hemoglobin blood levels and spectroscopic measurements. The slightly lower correlation coefficient for the capillary samples demonstrates a naturally higher variance in these values due to the laboratory method. PMID- 20588065 TI - Pneumothorax in a preterm infant monitored by electrical impedance tomography: a case report. AB - Electrical impedance tomography (EIT) is a noninvasive bedside tool for monitoring regional changes in ventilation. We report, for the first time, the EIT images of a ventilated preterm infant with a unilateral pneumothorax, showing a loss of regional ventilation in the affected lung during both high-frequency oscillation and spontaneous ventilation. PMID- 20588066 TI - Low pulmonary expression of epithelial Na(+) channel and Na(+), K(+)-ATPase in newborn infants with congenital diaphragmatic hernia. AB - BACKGROUND: It has been suggested from several animal studies and clinical observations that congenital diaphragmatic hernia (CDH) with pulmonary hypoplasia is accompanied by a disturbed perinatal ion transport. This could lead to respiratory distress due to slower clearance of fetal lung fluid at birth. OBJECTIVES: The purpose of this study was to determine whether CDH is related to changes in the expression of three rate-limiting transporter proteins in lung epithelium at birth. METHODS: Tracheal aspirate was collected from 12 newborn infants with CDH and from 8 newborn control patients. Sampling was performed at postnatal age 18 and at 43 h in the CDH group and at 18 h in the control group. The protein abundance of alpha-, beta- and gamma-epithelial Na(+) channel (ENaC), aquaporin 5 and Na(+), K(+)-ATPase alpha(1) was analyzed using semiquantitative immunoblotting. RESULTS: The levels of beta-ENaC, gamma-ENaC and Na(+), K(+) ATPase alpha(1) collected at 18 h postnatally were significantly lower in CDH infants compared to control infants. In the CDH group, no significant difference in the expression of the ENaC subunits, Na(+), K(+)-ATPase alpha(1) or aquaporin 5 could be detected between the two sampling time points. CONCLUSIONS: This downregulation may result in an abnormal lung fluid absorption which could be an important mechanism behind the respiratory distress seen in newborn CDH patients. PMID- 20588067 TI - Risk factors associated with development of persistent coagulase-negative staphylococci bacteremia in the neonate and associated short-term and discharge morbidities. AB - BACKGROUND: Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in neonatal intensive care unit settings. Historically, authors have questioned the clinical significance of these bacteremia episodes. Recently, clusters of CoNS bacteremia associated with significant morbidity have been reported. The frequency and importance of these clusters of bacteremia and their associated morbidity remains unclear. OBJECTIVE: We studied a prolonged cluster of 52 cases of persistent CoNS bacteremia in a level III neonatal intensive care unit to clarify risk factors, morbidity and outcomes associated with persistent CoNS bacteremia. STUDY DESIGN: A retrospective case-control study of infants with CoNS bacteremia >48 h after initiation of appropriate antibiotics and gestational age-matched control infants was performed. We reviewed patient characteristics prior to and during bacteremia, and outcomes at discharge or death. RESULTS: Persistently infected infants were significantly more likely to have greater duration of exposure to parenteral nutrition, hydrocortisone, antibiotics, and mechanical ventilation prior to infection. Persistently infected infants were significantly more likely than controls to experience feeding intolerance and to require inotropic support, increased respiratory support, and blood product transfusion during bacteremia. Infants with persistent CoNS bacteremia took longer to achieve full enteral feeds, had higher rates of chronic lung disease and increased length of stay compared to controls. No significant difference in mortality was noted. CONCLUSIONS: Persistent CoNS bacteremia is associated with clinically significant morbidity including feeding intolerance, respiratory failure, blood transfusion and chronic lung disease in this patient population. This impacts hospital course, increases length of stay and impacts medical needs after discharge. During this study, CoNS bacteremia was difficult to clinically eradicate despite in vitro antibiotic susceptibility. PMID- 20588068 TI - Persistent pulmonary hypertension of the newborn successfully treated with beraprost sodium: a retrospective chart review. AB - BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is one of the most serious conditions in neonates resulting in a high mortality and morbidity. New alternative therapies for PPHN have been sought to improve survival and reduce morbidity. OBJECTIVES: To report an initial experience of using beraprost sodium (BPS) to treat infants with PPHN and to assess its effect on oxygenation and hemodynamic stability over a 72-hour study period. METHODS: The clinical data of neonates who received BPS as an adjunctive therapy for PPHN in our hospital between July 2007 and June 2008 were retrospectively reviewed. RESULTS: During the study period, 7 infants with PPHN were successfully treated with BPS. The mean gestational age and birth weight were 39.3 +/- 1.5 weeks and 3,365.7 +/- 569.8 g, respectively. BPS was initiated at a median age of 42.7 h after birth (range: 2.1-166.5 h) with a baseline mean oxygen index (OI) of 33.9 +/- 15.7 and a baseline mean systolic blood pressure (SBP) of 79.4 +/- 9.9 mm Hg. The mean difference of OI at 24, 48 and 72 h following the treatment was -15.7 +/- 14.8 (p = 0.043), -18.2 +/- 12.3 (p = 0.018) and -16.7 +/- 17.5 (p = 0.042), respectively. The mean SBP was significantly reduced as early as 6 h after initiation of treatment (-11.1 +/- 11.5 mm Hg, p = 0.034) without changes in heart rate. Three cases were complicated with chronic lung disease, and the remaining 4 cases were normal at hospital discharge. No neurodevelopmental and cardiopulmonary disorders were observed in all cases at 1 year of age. CONCLUSIONS: BPS may be used as an alternative treatment for infants with PPHN giving a significant improvement in oxygenation. PMID- 20588069 TI - Evaluation of potential factors predicting attainment of full gavage feedings in preterm infants. AB - BACKGROUND: The clinical measures of gastric residuals and abdominal distention are often used to guide feeding in preterm infants, but there are few data demonstrating their usefulness. Similarly, techniques are now available to investigate gastrointestinal (GI) function noninvasively and safely, but their ability to predict attainment of full gavage feedings and/or feeding volume in preterm infants is unclear. OBJECTIVE: We sought to determine prospectively the potential relationships of attainment of full gavage feedings and feeding volume with clinical measures and noninvasive GI tests. METHODS: Fifty preterm infants were followed prospectively. Daily tally was taken of gavage feeding intake, gastric residual volumes (GRVs; milliliters per day, number of GRVs >50% of the previous feeding volume, and number of GRVs >2 ml/kg), and abdominal distention. Infants underwent repeated measurement of lactase activity, GI permeability, fecal calprotectin concentration, and gastric emptying. RESULTS: The number of GRVs >2 ml/kg tended to decrease with postnatal age (p = 0.06). Lactase activity and feeding volume in milliliters per kilogram per day prior to achieving full feedings were correlated (p = 0.007, beta = 0.164). There was no correlation between feeding outcomes and GRV (ml/day), GRV >50%, GRV >2 ml/kg, small bowel, colonic, or whole bowel permeability, fecal calprotectin concentration, gastric emptying, or abdominal distention. CONCLUSIONS: GRV is unreliable in predicting attainment of full gavage feeding. Lactase activity is related to feeding volume. However, other noninvasive GI tests utilized were not predictive. These data cast doubt upon the utility of GRV in guiding feeding therapy. Randomized trials of different GRV management protocols are needed. PMID- 20588070 TI - Functional polymorphism of cyclooxygenase-2 gene (G-765C) in depressive patients. AB - BACKGROUND: Depressive disorder (DD) is characterized by an inflammatory process and oxidative stress. Cyclooxygenase-2 (COX-2), the expression of which increases in depression, is an enzyme involved in inflammation and free radical processes. The aim of our study was to assess the correlation between single nucleotide polymorphism G-765C of the COX-2 gene and recurrent DD. METHODS: The study was carried out in a group of 181 patients treated for recurrent DD, and in 149 healthy subjects of the control group (CG). Polymerase chain reaction/restriction fragment length polymorphism was used for genotyping. RESULTS: A statistically significant difference in genotype distribution was observed as a result of the comparison between the CG and the patients with DD. We demonstrated that the presence of the -765G allele in the COX-2 gene increased 2.1-fold the risk of DD development, whereas the presence of a homozygote (G-765G) in the analyzed gene increased the risk of DD development 2.5-fold. CONCLUSION: According to the obtained results, it may be proposed with some caution that the presence of both the -765G allele and the G-765G genotype in the COX-2 gene may confer a susceptibility to an increased risk of recurrent DD in the Polish population. PMID- 20588071 TI - Norepinephrine and serotonin transporter genes: impact on treatment response in depression. AB - BACKGROUND/AIMS: The norepinephrine transporter (NET) and serotonin transporter (5-HTT) genes constitute promising candidate genes in major depression. Seven polymorphisms in the promoter, intronic and exonic region of the NET gene, as well as serotonin-transporter-linked promoter region (5-HTTLPR) and 5-HTT rs25531 polymorphisms were analyzed with respect to antidepressant treatment response with particular attention to gender effects and subtypes of melancholic or anxious depression. METHODS: 252 unrelated Caucasian patients (f = 142; m = 110) with major depression were genotyped for NET and 5-HTT polymorphisms. Genotype effects on Hamilton Depression Rating Scale score changes over 6 weeks of antidepressant treatment were analyzed using analysis of covariance with repeated measures. RESULTS: There was no effect of any of the 7 investigated NET, or the two 5-HTT polymorphisms, on the overall treatment response. An additional -/CT insertion/deletion (ins/del) polymorphism (rs58532686), however, was significantly associated with melancholic depression, with a better response in 12 patients carrying the deletion. Stratification for anxious versus nonanxious depression revealed a significantly detrimental effect of the less active 5 HTTLPR S allele (p = 0.007) and 5-HTTLPR/5-HTT rs25531 haplotypes on treatment response in patients with anxious depression. CONCLUSION: The present findings do not support a major impact of the NET and 5-HTT genes on antidepressant treatment response in major depression per se. However, there might be an impact of a -/CT ins/del polymorphism in the enhancer domain of the NET gene on treatment response in melancholic depression, which remains to be functionally investigated in future studies. The observed significant influence of the 5-HTT gene variation on antidepressant treatment in anxious depression points to anxious depression as a potential diagnostic entity of its own, requiring specific diagnostic and therapeutic attention. PMID- 20588072 TI - Basal Ganglia activity in pathological gambling: a fluorodeoxyglucose-positron emission tomography study. AB - BACKGROUND: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex. We extended our studies to include functional alterations of the striatum and thalamus in a cohort of patients with PG before and after treatment with lithium. METHODS: Twenty-one patients with PG who met lifetime comorbid bipolar spectrum diagnoses and a comparison group of 21 age- and sex matched controls underwent a baseline positron emission tomography (PET) scan. Sixteen of these patients entered a randomized double-blind placebo-controlled parallel-group-design trial of lithium and underwent a follow-up PET scan at week 10. Anatomical MRI were obtained and the structures outlined on consecutive axial slices. These individual hand-drawn templates were used to identify structures on the PET scan of each patient, and the rGMR was measured. RESULTS: The PG patients had a decrement of the rGMR in the ventral parts of the striatum and thalamus, and an increment of the rGMR in the dorsal parts as compared with the controls. Lithium treatment increased the ventral caudate rGMR to a trend level in the patients, but had no effect on the metabolism of either the putamen or the thalamus. CONCLUSION: Because of their extensive connectivity to the frontal cortex, striatal and thalamic functional alteration may contribute to faulty decision making processes in PG patients. By increasing the ventral rGMR of the caudate nucleus, lithium treatment may reduce cognitive dysfunction and symptoms in PG patients. PMID- 20588073 TI - Influence of CYP2D6 deletion, multiplication, -1584C-->G, 31G-->A and 2988G-->a gene polymorphisms on dextromethorphan metabolism among Mexican tepehuanos and mestizos. AB - The aim of this study was to explain the variability of CYP2D6 activity by the identification of CYP2D6 deletion and multiplications, and the single-nucleotide polymorphisms (SNPs) -1584C-->G, 31G-->A and 2988G-->A in Mexican Mestizo and Tepehuano subjects. One hundred twelve Mestizos and 99 Tepehuano Amerindians were studied, who were previously phenotyped with dextromethorphan. The frequencies of CYP2D6*2A [-1584C-->G] and *35 [-1584C-->G, 31G-->A] were 10.7 and 4.1%, respectively, in Mestizos, which is evidently a trend towards an extensive metabolism in carriers of the -1584G change. In Tepehuanos, *2A was identified with a frequency of 20%, and the allele *35 was not found. The frequencies of CYP2D6*5 (deletion) and *41[2988G-->A] were 1.3 and 2.2% in Mestizos and 0.5 and 1% in Tepehuanos, respectively. The SNP 2988A was found to be significantly related with the intermediate metabolizer phenotype in Mestizos (R = 0.309; n = 88; p = 0.006). The multiplications had frequencies of 4.1% in Mestizos and 1.5% in Tepehuanos. Only in the Mestizos did the presence of multiplications significantly decrease the DM/DX (dextromethorphan/dextrorphan) values (R = 0.273; n = 88; p = 0.016). The polymorphisms studied had different frequencies between Tepehuanos and Mestizos (p < 0.001); however, in the Tepehuano group these had a low influence on their phenotypic expression. It helps to understand the genotype-phenotype relationships of CYP2D6 in our studied populations. PMID- 20588075 TI - Introduction: the age of personal genomics? PMID- 20588074 TI - Protective effect of resveratrol on agonist-dependent regulation of vascular contractility via inhibition of rho-kinase activity. AB - The present study was undertaken to investigate the influence of resveratrol on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Resveratrol at a low concentration (0.03 mmol/l) relaxed directly and more markedly fluoride-induced vascular contraction than phorbol ester-induced contraction. Furthermore, resveratrol more markedly inhibited fluoride-induced increases in pMYPT1 levels than phorbol ester-induced increases. It also more markedly inhibited fluoride induced increases in pMYPT1 levels than pERK1/2 levels, suggesting that the mechanism involved the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of resveratrol on agonist-induced vascular contraction regardless of endothelial function. PMID- 20588076 TI - Myths, misconceptions and myopia: searching for clarity in the debate about the regulation of consumer genetics. AB - The new wave of companies offering genome scans direct-to-consumer (DTC) has prompted commentary from scientists, clinicians, bioethicists and those interested in the ethical, legal and social issues arising from genomics. It has thus brought a far wider range of actors into a longstanding debate about the regulation of genetic tests. However, some of the recent discussion is characterised by misunderstanding of the regulatory landscape, a failure to grasp the lessons of the past and lack of clarity of thought. In this commentary I challenge a series of myths and misconceptions which plague current academic and policy discussion: the conflation of regulation and proscription; the failure to recognise that DTC companies are gatekeepers; the assumption that requiring a medical intermediary for testing is paternalistic; the belief that online services cannot be regulated; the presumption that we must avoid genetic exceptionalism; the idea that policy is lagging behind science or that it is too soon to act; and finally, the view that DTC genetics is a reality we have to adapt to. PMID- 20588077 TI - Trigeminal nucleus caudalis anatomy: guidance for radiofrequency dorsal root entry zone lesioning. AB - OBJECT: This study seeks to improve the accuracy of trigeminal nucleus caudalis dorsal root entry zone (DREZ) radiofrequency lesioning by quantifying the size and orientation of the nucleus caudalis. METHODS: Using serial axial photographs of 6 formalin-fixed cadaver brainstems, digital nucleus caudalis measurements were taken at 1-mm intervals from the level of the obex to the C(2) dorsal nerve roots. RESULTS: From the obex to the C(2) dorsal nerve roots, the nucleus caudalis decreases in width (from 2.6 +/- 0.2 to 1.0 +/- 0.3 mm) and, excluding superficial tract thickness, decreases in axial nucleus depth (from 2.4 +/- 0.3 to 1.7 +/- 0.2 mm). At levels between the obex and 10 mm caudal to the obex, the accessory nerve rootlets exit the brainstem at the junction of the spinal trigeminal tract and the dorsal spinocerebellar tract. CONCLUSION: This study details the anatomic dimensions and orientation of the nucleus caudalis for surgeons who perform DREZ lesioning. PMID- 20588078 TI - Stereotactic approach to the trigeminal ganglion using a stereotactic frame and intraoperative computed tomography scans: technical note. AB - OBJECTIVE: In this paper, a technique to place a probe at the trigeminal ganglion using a stereotactic frame and intraoperative computed tomography (CT) scans is described. METHOD: The procedure is performed on the CT table using a stereotactic frame. After the coordinates have been obtained and then adjusted, the target is probed using the frame. In this study, intraoperative scans were obtained to confirm the accuracy of probe placement. After successful stimulation studies, radiofrequency lesions were made. Thirty-two procedures were performed on 26 patients. RESULTS: Twenty patients were free of pain at a follow-up which lasted a median of 30 months. There was no permanent complication from the procedure. CONCLUSIONS: The technique is straightforward, accurate and safe. It also enables the surgeon to obtain intraoperative confirmation of accurate probe placement on CT images. PMID- 20588079 TI - Closed-loop stimulation in the control of focal epilepsy of insular origin. AB - BACKGROUND: Previous studies have shown that closed-loop or responsive neurostimulation can abort induced or spontaneous epileptiform discharges. OBJECTIVE: To assess the effectiveness of a programmable cranially implanted closed-loop neurostimulation system in the control of seizures originating from an area relatively inaccessible by open craniotomy. METHOD: A patient with drug resistant partial epilepsy had previously undergone open resection of the left frontal opercular cortex and the underlying insular area. Although subdural-depth electrode ictal recordings had been nonlocalizing, depth electrode insular stimulation had produced the patient's habitual aura. Postoperatively, there was a sustained 50% reduction in seizure frequency. The residual seizures were identical to the preoperative seizures. Repeat depth electrode monitoring revealed that the ictal focus was immediately posterior to the previously resected insular area. A closed-loop cranial internal pulse generator system including left anterior insular and posterior orbitofrontal depth electrodes was implanted. RESULT: There was an additional 60% reduction of seizures. CONCLUSION: Preliminary observation indicates that responsive neurostimulation may be an effective alternative to higher-risk resective epilepsy surgery. PMID- 20588080 TI - Analysis of stereotactic accuracy of the cosman-robert-wells frame and nexframe frameless systems in deep brain stimulation surgery. AB - INTRODUCTION: The primary goal of stereotactic systems in deep brain stimulation (DBS) surgery is accurate delivery of a DBS lead to a target identified on imaging. Thus, it is critical to understand the accuracy of the stereotactic systems and the factors which may be associated with a decrease in accuracy. METHODS: Ninety patients underwent microelectrode recording-guided placement of 139 DBS leads by a single surgeon using the Cosman-Roberts-Wells (CRW) frame (n = 70) or a frameless skull-mounted trajectory guide (Nexframe; n = 69). The final DBS location was identified on a postoperative CT fused to the preoperative CT and MRI scans. The difference between this final location and the expected location was calculated. RESULTS: The vector error was 2.65 mm (standard error, 0.22) for the frame and 2.78 mm (standard error, 0.25) for the frameless methods (p = 0.69). There was a gradual decline in error for both systems over time, as the vector error of the last 20 implants was 1.99 for the CRW frame and 2.04 for the Nexframe (p = 0.86). CONCLUSIONS: This study shows that the CRW frame and Nexframe frameless systems have equivalent accuracy. Furthermore, the accuracy of both techniques improved over time, from 3 mm initially to 2 mm with current techniques. PMID- 20588081 TI - Avoidance and management of surgical and hardware-related complications of deep brain stimulation. AB - OBJECTIVE: Although deep brain stimulation (DBS) is nonablative, it may give rise to many complications. In order to identify and reduce factors contributing to the complications, we performed a retrospective analysis of patients who received DBS in our institution over a 9-year period from March 2000 to December 2008. METHODS: Included in this study were 161 patients (85 male and 76 female). Data from these patients were collected and analyzed with respect to the complications and factors potentially related to these complications. RESULTS: A total of 25 surgical and hardware-related complications occurred in 24 patients, including confusion in 11 cases (6.83%), asymptomatic intracranial hemorrhage in 1 case (0.62%), electrode misplacement in 2 cases (1.24%), infection of the subcutaneous pocket receiving the pulse generator in 1 case (0.62%), skin erosion in 2 cases (1.24%), pulse generator seroma formation in 6 cases (3.72%), and device malfunction in 1 case (0.62%). There was no permanent neurological deficit. CONCLUSION: Confusion is the most common complication in simultaneous bilateral DBS targeting the subthalamic nucleus, especially in patients with severe Parkinson's disease. With increasing experience of surgeons, complete obedience to intraoperative surgical routines and reasonable application of the microelectrode recording technique, other complications could also be reduced. PMID- 20588082 TI - Long-term benefit sustained after bilateral pallidal deep brain stimulation in patients with refractory tardive dystonia. AB - BACKGROUND/AIMS: Tardive dystonia (TD) can be a highly disabling, permanent condition related to the use of dopamine-receptor-blocking medications. Our aim was to evaluate the long-term effect of bilateral pallidal deep brain stimulation (DBS) for TD. METHODS: Five consecutive patients with disabling TD who underwent stereotactic placement of bilateral globus pallidus internus DBS leads were included. All patients had a history of mood disorder or schizophrenia previously treated with neuroleptic medication, with a mean duration of motor symptoms of 10.2 years. Dystonia severity was measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score by a blinded neurologist reviewing pre- and postoperative videotaped examinations. RESULTS: The mean baseline movement BFMDRS score was 49.7 (range 20-88). Overall, we observed a mean reduction of 62% in the BFMDRS movement score within the first year after surgery. Persistent improvement in dystonia (71%) was seen at the last follow-up ranging from 2 to 8 years after surgery. CONCLUSION: Our experience suggests that pallidal DBS can be an effective therapy with long-term benefits for patients with TD. PMID- 20588083 TI - Development of an in vitro modified skin absorption test for the investigation of the follicular penetration pathway of caffeine. AB - The Organization for Economic Cooperation and Development (OECD) recommends caffeine as a reference substance for in vitro skin absorption tests using Franz diffusion cells (FDC). However, it has not been possible to investigate the follicular penetration pathway using this method until now. The aim of this study was to develop a technique to allow the examination of the follicular penetration pathway of a substance penetrating into the skin. The OECD standard method was therefore combined with the follicle closing technique (FCT), an established in vivo method. By using test skin of varying follicular densities, different penetration values were obtained for the test substance caffeine. The follicular penetration rate was determined by an indirect calculation after modifying the in vivo FCT for use in the in vitro FDC. This method is the first to allow the differentiation of penetration pathways by combining the OECD standard method (using the FDC) and the FCT. Caffeine showed a surprisingly high rate of penetration through the follicular shunts in vitro. PMID- 20588084 TI - Antiseptic efficacy and tolerance of tissue-tolerable plasma compared with two wound antiseptics on artificially bacterially contaminated eyes from commercially slaughtered pigs. AB - AIM: To compare the tissue tolerance and efficacy of two wound antiseptics with tissue-tolerable plasma (TTP) on enucleated contaminated eyes from slaughtered pigs in order to draw consequences for the use of TTP on wounds. METHOD: The corneas of extracted eyes were contaminated with Staphylococcus aureus or Pseudomonas aeruginosa. One and 10 min after application of 10% povidone (PVP) iodine and 0.04% polyhexanide, respectively, the eyes were rinsed with inactivating solution. To test TTP, the plasma pen meandered over the eyes at a speed of 30 mm/s and a distance of 5 mm; the eyes were then rinsed with balanced salt solution. The reduction factor was calculated by the difference between the logarithm of colony-forming units in the rinse before and after antisepsis or TTP application. RESULTS: The efficacy of TTP (reduction factor 2.4-2.9) was significantly higher (p < 0.001) than that of PVP-iodine and polyhexanide (reduction factor 1.7-2.1). CONCLUSION: TTP is more effective than the tested wound antiseptics. The lack of histological damage to the eyes of slaughtered pigs would seem to make its use as a wound antiseptic a viable alternative. In contrast to antiseptics, it supplies additional energy in the form of heat, electric fields and radicals by TTP. PMID- 20588085 TI - Modest but increased penetration through damaged skin: an overview of the in vivo human model. AB - BACKGROUND/AIM: Quantifying percutaneous penetration of topical drugs as well as those compounds relevant to occupational exposure is important for assessing their delivery, efficacy and toxicology. Methods for assessing penetration are established for intact skin; however, what may be equally relevant is how much penetration occurs through damaged skin. METHODS: The Embase database was accessed online in March 2009 in search of human in vivo studies measuring penetration through damaged or diseased skin. RESULTS: Few studies have measured penetration through damaged human skin in vivo. A majority demonstrate a modest enhancement in penetration, with the exception of microdialysis studies that show a significant enhancement. The enhancement generally favored hydrophilic molecules over lipophilic molecules. CONCLUSIONS: Damaged or diseased skin may display a modest increase in penetration compared to intact skin, which is dependent on the method of measurement; however, additional studies with consistent methods are needed to fully elucidate how much penetration occurs through the many types and degrees of damaged skin. PMID- 20588086 TI - Expression of cathepsins in human skin photoaging. AB - Cathepsins are involved in regulatory mechanisms in human skin, but their role in photoaged skin remains unknown. This study investigates the role of cathepsin B, D, K, and G in skin photoaging in vivo and in vitro. Cathepsin-induced changes in skin as a result of chronic UV irradiation were detected by immunohistochemistry methods. Protein cathepsin expressions in UVA-induced premature senescence in fibroblasts in vitro were detected by Western blot technique. Cathepsin mRNA expression in photoaged skin and fibroblasts was detected by real-time reverse transcription-polymerase chain reaction. Immunohistochemistry and Western blot show lower protein expression of cathepsin B, D, and K in photoaged skin and fibroblasts, while cathepsin G was higher. The mRNA expression of cathepsin B, D, and K of the photoaged skin in vivo decreased to 20 +/- 0.5, 25 +/- 1.6 and 22 +/ 0.8%, while cathepsin G mRNA increased to 2.24 +/- 0.09 times that of control. In photoaged fibroblasts, cathepsin B, D, and K mRNA was downregulated to 64 +/- 2.9, 24 +/- 2.1 and 9 +/- 0.5% while cathepsin G mRNA was upregulated to 1.42 +/- 0.06 times that of control fibroblasts. These experiments suggest that cathepsin B, D, K, and G may act as biomarkers in photoaged human skin. PMID- 20588087 TI - Can misdiagnosis in pre-operative FNAC of thyroid nodule influence surgical treatment? AB - BACKGROUND: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision. MATERIALS AND METHODS: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology. Each cytological diagnosis was compared to results obtained by definitive histology. Tumors were called incidentalomas if they consisted of a neoplastic focus with a low grade of aggressiveness, as demonstrated by dimension <5 mm, non-aggressive histological subtype. RESULTS: Of the 541 cases of benign disease, 417 were confirmed as benign. The other 124 cases are listed as follows: 29 follicular adenoma; 76 papillary carcinoma (35 found as incidentalomas), and 19 follicular carcinoma (3 incidentalomas). Cytology suggestive of papillary carcinoma was correct in 95.2% of cases (119/125). The 135 tumors termed "follicular neoplasm" were staged on pathology thus: 56 adenoma (41.4%), 26 carcinoma (19.2%), 13 (9.6%) absence of follicular proliferation, 38 (28.1%) papillary follicular variant, 2 (1.4%) undifferentiated cells. Medullary carcinomas were both confirmed. The "suspicious group" exhibited no malignancy on fine needle aspiration cytology (12 of 21; 57%). CONCLUSIONS: Cytology has good reliability in malignant lesions. Incidental tumors occurring in benign disease have little impact on clinical and surgical management; "follicular neoplasm" posed two problems - the impossibility of identifying the nature of the tumor, as well as the newer difficulty in distinguishing papillary follicular subtype. PMID- 20588088 TI - Opportunities. PMID- 20588089 TI - From Cawthorne-Cooksey to biotechnology: where we have been and where we are headed in vestibular rehabilitation? PMID- 20588090 TI - Efficacy of gaze stability exercises in older adults with dizziness. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether the addition of gaze stability exercises to balance rehabilitation would lead to greater improvements of symptoms and postural stability in older adults with normal vestibular function who reported dizziness. METHODS: Participants who were referred to outpatient physical therapy for dizziness were randomly assigned to the gaze stabilization (GS) group (n = 20) or control (CON) group (n = 19). Dizziness was defined as symptoms of unsteadiness, spinning, a sense of movement, or lightheadedness. Participants were evaluated at baseline and discharge on symptoms, balance confidence, visual acuity during head movement, balance, and gait measures. The GS group performed vestibular adaptation and substitution exercises designed to improve gaze stability, and the CON group performed placebo eye exercises designed to be vestibular neutral. In addition, both groups performed balance and gait exercises. RESULTS: There were no baseline differences (P > .05) between the GS and CON groups in age, sex, affect, physical activity level, or any outcome measures. Both groups improved significantly in all outcome measures with the exception of perceived disequilibrium. However, there was a significant interaction for fall risk as measured by Dynamic Gait Index (P = .026) such that the GS group demonstrated a significantly greater reduction in fall risk compared with the CON group (90% of the GS group demonstrated a clinically significant improvement in fall risk versus 50% of the CON group). DISCUSSION AND CONCLUSIONS: This study provides evidence that in older adults with symptoms of dizziness and no documented vestibular deficits, the addition of vestibular-specific gaze stability exercises to standard balance rehabilitation results in greater reduction in fall risk. PMID- 20588091 TI - Does otolith organ dysfunction influence outcomes after a customized program of vestibular rehabilitation? AB - BACKGROUND AND PURPOSE: Vestibular rehabilitation (VR) is a successful approach to the treatment of vestibular dysfunction. The purpose of this study was to investigate the influence of otolith dysfunction on the response to VR in individuals with a peripheral vestibular disorder. PARTICIPANTS AND METHODS: Eighteen participants with loss of semicircular canal function only, and 29 participants with combined loss of semicircular canal and otolith organ function were recruited. All participants received a comprehensive clinical assessment before and after an 8-week customized program of VR. RESULTS: Both groups achieved significant improvements on most measures at the end of the 8-week VR program. However, no significant differences were identified between participants with versus without otolith dysfunction with respect to change in symptom severity (P = .81), self-perceived handicap (P = .92), functional limitations (P = .93), or balance performance after VR. DISCUSSION AND CONCLUSIONS: Otolith dysfunction does not significantly influence the response to rehabilitation of individuals with a peripheral vestibular disorder. Vestibular rehabilitation is associated improvements in symptom severity, self-perceived handicap, and balance function in individuals with otolith dysfunction. PMID- 20588092 TI - Perceptual and motor inhibition in individuals with vestibular disorders. AB - BACKGROUND AND PURPOSE: Vestibular dysfunction has been shown to be associated with altered cognitive function. The purpose of this study was to examine changes in cognitive function in participants with vestibular disease during the course of vestibular physical therapy. METHODS: Twenty-two participants (mean age = 52, standard deviation = 11) with previously diagnosed vestibular disorders were tested at the beginning and end of rehabilitation. The Motor and Perceptual Inhibition Test (MAPIT) was used to assess manual reaction times when responding to various stimuli presented on a computer screen. Additional physical performance measures and questionnaires related to dizziness, fear of falling, and activities of daily living were used to quantify change during the 6-week intervention period. The repeatable battery for the assessment of neuropsychological status (a measure of memory and executive function) was used to ensure that participants did not have memory or executive function deficits. RESULTS: Overall, there were no significant differences in MAPIT score before versus after physical therapy intervention, however there were some participants who demonstrated improvements in motor inhibition (MI) and perceptual inhibition (PI) scores. Interstingly, 8 of the 9 participants with abnormal caloric test findings had improvements on 2 of the PI scores. Overall 50% to 64% of the participants demonstrated improvement in the 4 different MAPIT scores. There were improvements in physical performance and self-report measures at the end of the 6 week physical therapy intervention program. DISCUSSION/CONCLUSION: Individuals with vestibular disorders may show improvement in MI and PI after a 6-week physical therapy intervention program; those with abnormalities on caloric and rotational chair tests appear especially likely to experience improvement in PI. Additional study is needed to determine whether individuals with vestibular disorders have remediable deficits in MI and PI. PMID- 20588093 TI - High-velocity angular vestibulo-ocular reflex adaptation to position error signals. AB - BACKGROUND AND PURPOSE: Vestibular rehabilitation strategies including gaze stabilization exercises have been shown to increase gain of the angular vestibulo ocular reflex (aVOR) using a retinal slip error signal (ES). The identification of additional ESs capable of promoting substitution strategies or aVOR adaptation is an important goal in the management of vestibular hypofunction. Position ESs have been shown to increase both aVOR gain and recruitment of compensatory saccades (CSs) during passive whole body rotation. This may be a useful compensatory strategy for gaze instability during active head rotation as well. In vestibular rehabilitation, the imaginary target exercise is often prescribed to improve gaze stability. This exercise uses a position ES; however, the mechanism for its effect has not been investigated. We compared aVOR gain adaptation using 2 types of small position ES: constant versus incremental. METHODS: Ten subjects with normal vestibular function were assessed with unpredictable and active head rotations before and after a 20-minute training session. Subjects performed 9 epochs of 40 active, high-velocity head impulses using a position ES stimulus to increase aVOR gain. RESULTS: Five subjects demonstrated significant aVOR gain increases with the constant-position ES (mean, 2%; range, -18% to 12%) compared with another 5 subjects showing significant aVOR gain increases to the incremental-position ES (mean, 3.7%; range, -2% to 22.6%). There was no difference in aVOR gain adaptation or CS recruitment between the 2 paradigms. DISCUSSION AND CONCLUSION: These findings suggest that some subjects can increase their aVOR gain in response to high-velocity active head movement training using a position ES. The primary mechanism for this seems to be aVOR gain adaptation because CS use was not modified. The overall low change in aVOR gain adaptation with position ES suggests that retinal slip is a more powerful aVOR gain modifier. PMID- 20588094 TI - Vestibular rehabilitation for dizziness and balance disorders after concussion. AB - BACKGROUND AND PURPOSE: Management of dizziness and balance dysfunction is a major challenge after concussion. The purpose of this study was to examine the effect of vestibular rehabilitation in reducing dizziness and to improve gait and balance function in people after concussion. METHODS: A retrospective chart review of 114 patients (67 children aged 18 years and younger [mean, 16 years; range, 8-18 years]; 47 adults older than 18 years [mean, 41 years; range, 19-73 years]) referred for vestibular rehabilitation after concussion was performed. At the time of initial evaluation and discharge, recordings were made of outcome measures of self-report (eg, dizziness severity, Activities-specific Balance Confidence Scale, and Dizziness Handicap Inventory) and gait and balance performance (eg, Dynamic Gait Index, gait speed, and the Sensory Organization Test). A mixed-factor repeated-measures analysis of variance was used to test whether there was an effect of vestibular rehabilitation therapy and age on the outcome measures. RESULTS: The median length of time between concussion and initial evaluation was 61 days. Of the 114 patients who were referred, 84 returned for at least 1 visit. In these patients, improvements were observed in all self-report, gait, and balance performance measures at the time of discharge (P < .05). Children improved by a greater amount in dizziness severity (P = .005) and conditions 1 (eyes open, fixed support) and 2 (eyes closed, fixed support) of the Sensory Organization Test (P < .025). DISCUSSION: Vestibular rehabilitation may reduce dizziness and improve gait and balance function after concussion. For most measures, the improvement did not depend on age, indicating that vestibular rehabilitation may equally benefit both children and adults. CONCLUSIONS: Vestibular rehabilitation should be considered in the management of individuals post concussion who have dizziness and gait and balance dysfunction that do not resolve with rest. PMID- 20588095 TI - Tracking recovery of vestibular function in individuals with blast-induced head trauma using vestibular-visual-cognitive interaction tests. AB - BACKGROUND AND PURPOSE: Traumatic brain injury secondary to blast exposure is a significant international concern and a growing rehabilitation issue. Our objective was to determine whether a novel battery of vestibular-visual-cognitive interaction tests provides objective data to document functioning, and the changes in functioning associated with vestibular physical therapy (VPT) treatment, in individuals with blast-induced balance disorder. METHODS: Eighty two individuals with blast-induced mild traumatic brain injury were evaluated at baseline using a set of vestibular-visual-cognitive tests. Testing was repeated at 4-week intervals after beginning VPT. The tests included static visual acuity, perception time, target acquisition, target following (TF), dynamic visual acuity (DVA), and gaze stabilization tests. The VPT program consisted of exercise procedures that targeted the vestibulo-ocular reflex, cervico-ocular reflex, and depth perception. Somatosensory balance exercises, dynamic gait, and aerobic function exercises were also included. Participants attended VPT twice weekly for 1-hour appointments and were instructed to perform the exercises at home on other days. Mean test values were determined and compared with normative values previously collected in our laboratory from individuals without vestibular dysfunction. RESULTS: Mean participant pre-VPT measures for perception time and target acquisition were similar to normative values, and there was no significant change in these measures. Initially, TF and DVA scores were below normative levels but returned to normative levels after 8 weeks of VPT. Gaze stabilization scores were below normative levels pre-VPT but improved by the time of the week 8 evaluation. CONCLUSIONS: This battery of vestibular-visual-cognitive tests seems to be reasonable to establish initial status and to evaluate participant progress associated with participation in VPT. Our data suggest meaningful improvement in TF and DVA after 8 weeks of treatment. A treatment period of 12 weeks or longer may be required for gaze stabilization scores to return to normative values. PMID- 20588096 TI - Application of vibrotactile feedback of body motion to improve rehabilitation in individuals with imbalance. AB - BACKGROUND AND PURPOSE: Balance rehabilitation and vestibular or balance prostheses are both emerging fields that have a potential for synergistic interaction. This article reviews vibrotactile prosthetic devices that have been developed to date and ongoing work related to the application of vibrotactile feedback for enhanced postural control. A vibrotactile feedback device developed in the author's laboratory is described. METHODS: Twelve subjects with vestibular hypofunction were tested on a platform that moved randomly in a plane, while receiving vibrotactile feedback in the anteroposterior direction. The feedback allowed subjects to significantly decrease their anteroposterior body tilt but did not change mediolateral tilt. A tandem walking task performed by subjects with vestibulopathies demonstrated a reduction in their mediolateral sway due to vibrotactile feedback of mediolateral body tilt, after controlling for the effects of task learning. Published findings from 2 additional experiments conducted in the laboratories of collaborating physical therapists are summarized. RESULTS: The Dynamic Gait Index scores in community-dwelling elderly individuals who were prone to falls were significantly improved with the use of mediolateral body tilt feedback. DISCUSSION AND CONCLUSIONS: Although more work is needed, these results suggest that vibrotactile tilt feedback of subjects' body motion can be used effectively by physical therapists for balance rehabilitation. A preliminary description of the third-generation device that has been reduced from a vest format to a belt format is described to demonstrate the progressive evolution from research to clinical application. PMID- 20588097 TI - The use of optokinetic stimulation in vestibular rehabilitation. AB - Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorienting visual stimuli (eg, supermarkets). Individuals with VV are believed to be overly reliant on visual input for balance (ie, visually dependent). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. However, the frequency of treatment sessions (twice weekly for 8 weeks) and the equipment used (expensive and space consuming) make it difficult to incorporate these techniques into everyday clinical practice where exercises may be practiced unsupervised. The aim of this focused review is to provide an overview of recent findings investigating (a) responses of individuals with vestibular deficits to a customized exercise program incorporating exposure to optokinetic stimuli via a "high-tech" visual environment rotator or a "low-tech" DVD with and without supervision, and (b) the mechanism of recovery. Optokinetic stimulation will also be discussed in relation to other new innovations in vestibular rehabilitation techniques and future work. PMID- 20588098 TI - The effects of habituation and gaze stability exercises in the treatment of unilateral vestibular hypofunction: a preliminary results. AB - BACKGROUND AND PURPOSE: The efficacy of both habituation and adaptation exercise interventions in the treatment of unilateral vestibular hypofunction has been demonstrated by previous studies. The purpose of this article is to describe the preliminary results of an ongoing study that compares the effects of these 2 different exercise approaches on outcomes related to vestibular function. METHODS: Seven participants with unilateral vestibular hypofunction completed a 6 week exercise intervention after random assignment to either habituation exercises or gaze stability (GS) adaptation exercises. The following measures were performed pre- and posttreatment: Dizziness Handicap Inventory to measure the symptom impact, motion sensitivity quotient (MSQ) to assess sensitivity to head movements, and the dynamic visual acuity (DVA) test as a measure of GS during head movements. RESULTS: After the 6-week intervention, there was an overall improvement in the Dizziness Handicap Inventory, the MSQ score, and both the active and passive DVA. The habituation and GS intervention group participants each demonstrated similar improvements in both the MSQ score and the active and passive DVA measures. DISCUSSION AND CONCLUSIONS: The improvement in the MSQ score for the GS group and the improvement in the DVA measures for the habituation group were unexpected findings. Head movement, which is required by both exercise interventions, rather than the specific type of exercise may be the critical factor underlying the observed improvements in motion sensitivity and DVA. PMID- 20588099 TI - Translational rehabilitation research: from science to practice and practice to science. PMID- 20588103 TI - Role of HIV-1 Tat in AIDS pathogenesis: its effects on cytokine dysregulation and contributions to the pathogenesis of opportunistic infection. PMID- 20588104 TI - Inflammatory biomarkers and abacavir use in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. AB - OBJECTIVE: To assess associations between abacavir (ABC) use and systemic inflammation. DESIGN: Nested case-control study. METHODS: The Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) cohort participants who initiated ABC were matched, using propensity score methods, to ABC-unexposed persons. Levels of high-sensitivity C-reactive protein (hsCRP) (microg/ml), interleukin-6 (IL-6) (pg/ml), and D-dimer (microg/ml) were measured from pre HAART and on-HAART plasma. Random-effects models compared markers by ABC exposure and by changes from pre-HAART levels. RESULTS: Biomarkers were measured in N = 508 matched pairs (328 women; 180 men). Pre-HAART levels did not differ by exposure group except that hsCRP levels were higher among WIHS women who subsequently used ABC (P = 0.04). Regardless of ABC use, mean hsCRP increases and D-dimer reductions were seen when comparing pre-HAART to on-HAART levels, in the overall group (28 and -27%), for MACS men (28 and -31%) and for WIHS women [29 and -24%, P < 0.01 for all]; IL-6 levels declined in MACS men (P = 0.02). No adjusted biomarker level differences existed by ABC exposure at the on-HAART visit. HIV RNA reductions correlated with D-dimer (r = 0.14, P < 0.01) and IL-6 (r = 0.12, P < 0.01) reductions. Associations between ABC use and mean biomarker levels were modified by pre-HAART antiretroviral therapy experience. Renal dysfunction was equally likely among non-ABC and ABC recipients. DISCUSSION: ABC use was not associated with plasma elevations in hsCRP, IL-6, and D-dimer. Mechanisms other than increased systemic inflammation may account for ABC's reported association with increased cardiovascular disease. HAART-associated reductions in D-dimer and IL-6 were apparent regardless of ABC use and were correlated with HIV RNA reductions. PMID- 20588105 TI - Postprandial lipid effects of low-dose ritonavir vs. raltegravir in HIV uninfected adults. AB - OBJECTIVE: Protease inhibitor therapy is associated with an increased risk of myocardial infarction. Half this risk appears attributable to fasting dyslipidemia, but half remains unexplained. We compared the fasting and postprandial effects of low-dose ritonavir and raltegravir on cardiovascular and metabolic risk factors. DESIGN: Randomized (1: 1), open-label study. METHODS: Twenty HIV-uninfected volunteers (14 women, mean age 32 years) received low-dose ritonavir (100 mg daily) or raltegravir (400 mg twice daily) for 4 weeks. We administered a standardized meal (3.6 MJ, 76% fat, 10% carbohydrates) at baseline and at week 4, with hourly assessments for 6 h after each meal. The primary outcome measure was incremental area under the curve (iAUC) change in postprandial lipids. RESULTS: Ritonavir induced significantly higher postprandial iAUC excursions in low-density lipoprotein (LDL) cholesterol than raltegravir, mostly in the first 3 h after food (P < 0.05). The ritonavir-related postprandial increases in LDL cholesterol at 1, 2, and 3 h were 30-65% greater than the ritonavir-related increase in fasting LDL cholesterol (0.34-0.43 vs. 0.26 mmol/l, P < 0.05 for each comparison). The postprandial iAUC and fasting LDL cholesterol changes at week 4 were significantly correlated (r = 0.64; P = 0.003). There was no between-group difference for other postprandial parameters. CONCLUSION: In HIV uninfected adults, postprandial LDL cholesterol excursions with low-dose ritonavir were significantly greater than those with raltegravir. This postprandial effect of ritonavir increased by about 50% the previously observed adverse effect of ritonavir on fasting LDL cholesterol, and so may explain some of the hitherto unexplained association of protease inhibitor-based therapy with cardiovascular disease. PMID- 20588107 TI - Acute renal failure due to immune reconstitution inflammatory interstitial nephritis in an HIV-positive patient. PMID- 20588106 TI - Hormonal contraception and HIV acquisition: reanalysis using marginal structural modeling. AB - Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition. Also, young (18-24 years) but not older women who used DMPA and COCs were at increased HIV risk. PMID- 20588108 TI - The benefits of early treatment for HIV. PMID- 20588109 TI - Is polygamy really benign? PMID- 20588110 TI - Benign concurrency in context and practice: a response to Epstein and Stanton. PMID- 20588111 TI - HIV infection and suicide in the era of HAART in England, Wales and Northern Ireland. PMID- 20588113 TI - Editorial: cystic fibrosis. PMID- 20588114 TI - Role of IL-1beta in type 2 diabetes. AB - PURPOSE OF REVIEW: To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL 1beta. RECENT FINDINGS: Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1beta as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1beta-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1beta itself. Caspase-1 is required for IL-1beta activity and the release of free fatty acids from the adipocyte. An emerging hypothesis gains support from patients with type 2 diabetes in which an imbalance in the amount of IL-1beta agonist activity versus the specific countering by the naturally occurring IL-1 receptor antagonist (IL-1Ra) determines the outcome of islet inflammation. An important confirmation comes from clinical trials. Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1beta antibodies, provides proof-of-principle data that reducing IL-1beta activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1beta-mediated inflammation in the microenvironment of the islet allows for regeneration. SUMMARY: Monotherapy or add-on therapy targeting IL-1beta in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events. PMID- 20588115 TI - The diagnosis and treatment of growth hormone deficiency in adults. AB - PURPOSE OF REVIEW: This review summarizes the recent published information regarding efficacy and complications of growth hormone replacement therapy. Several recent reports have monitored patients for periods of up to 10 years. Additionally, a consensus conference has been held regarding needed improvements in diagnostic testing and the recommendations of consensus panels regarding diagnostic criteria and laboratory test utilization are summarized. RECENT FINDINGS: Long-term studies show growth hormone can be administered safely and that muscle strength and function as well as lipoprotein abnormalities and low bone mineral density show sustained improvement over extended periods of time. The complications that occur are generally dose-dependent and once attenuated do not tend to recur. Long-term safety studies regarding improvement in cardiovascular mortality and/or worsening prognosis for patients who develop malignancies are available only in the form of observational studies and randomized controlled long-term trial information is not yet available. The studies reported provide a means for clinicians to ascertain the patients who are likely to derive the greatest benefit from growth hormone when the appropriate diagnostic testing and treatment paradigms are utilized. SUMMARY: The studies that are summarized provide useful information for assessing the response to treatment, selecting patients who are candidates for long-term replacement therapy and for selecting those in whom the need for therapy may need to be reassessed. PMID- 20588116 TI - Current world literature. PMID- 20588118 TI - Pupil response as an indication of effortful listening: the influence of sentence intelligibility. AB - OBJECTIVES: The aim of this study was to evaluate the influence of sentence intelligibility on the pupil dilation response during listening. Task-induced pupil-dilation reflects explicit effortful processing load. Therefore, pupillometry can be used to examine the listening effort during speech perception in difficult listening conditions. We expected to find increasing pupil dilation as a function of decreasing speech intelligibility. DESIGN: Thirty-eight young participants (mean age = 23 yrs, SD = 3.2 yrs) with normal hearing were included. They performed three speech reception threshold (SRT) tests in which they listened to sentences in stationary noise. A one-up-one-down, two-up-one-down, or four-up-one-down adaptive procedure was applied, resulting in the correct rehearsal of 50, 71, or 84% of the sentences (SRT(50%), SRT(71%), and SRT(84%), respectively). We examined the peak dilation amplitude, the latency of the peak dilation amplitude, and the mean pupil dilation during the processing of the speech in each of these conditions. The peak dilation amplitude and mean pupil dilation were calculated relative to the baseline pupil diameter during listening to noise alone. For each SRT condition, participants rated the experienced listening effort and estimated their performance level. RESULTS: The signal to noise ratios (SNRs) in the SRT(50%), SRT(71%), and SRT(84%) conditions increased as a function of the speech intelligibility level. The subjective effort ratings decreased, and the estimated performance increased with increasing speech intelligibility level. Repeated measures analyses of variance indicated that peak dilation amplitude and mean pupil dilation were higher in the SRT(50%) condition as compared with the SRT(71%) and SRT(84%) conditions. The peak dilation amplitude, mean pupil dilation, and peak latency increased with decreasing SNR of the speech in noise, but no effect of noise level by itself on the baseline pupil diameter was observed. Irrespective of SNR, the pupil response was higher for incorrectly repeated sentences than for correctly repeated sentences. The analyses also indicated condition-order effects on the peak dilation amplitude and mean pupil dilatation: the pupil response was higher in the first SRT test than in the second and third tests. Within the first and third test, the baseline pupil diameter and the mean pupil dilation decreased as a function of the sentence number within the test. Spearman correlation coefficients showed no relations among the SNRs at the SRTs, subjective ratings, and the pupil response. CONCLUSIONS: The peak dilation amplitude, peak latency, and mean pupil dilation systematically increase with decreasing speech intelligibility. These results support that listening effort, as indicated by the pupil response, increases with decreasing speech intelligibility. This study indicates that pupillometry can be used to examine how listeners reach a certain performance level. Application of this technique to study listening effort can yield valuable insight into the processing resources required across listening conditions and into the factors related to interindividual differences in speech perception in noise. PMID- 20588119 TI - Cochlear implant-mediated perception of nonlinguistic sounds. AB - OBJECTIVES: The overwhelming majority of test measures to assess cochlear implant (CI) candidacy, efficacy, and progress are based on speech perception. Nonlinguistic sounds, such as alerting and nonspeech human generated sounds, have received comparatively little attention, despite their central importance for daily living and environmental sound awareness. The purposes of this study were to develop and validate a beta test measure of nonlinguistic sound perception and to assess performance in CI users. DESIGN: A beta test of nonlinguistic sound perception, referred to as the NonLinguistic Sounds Test (NLST) was developed. The NLST consists of 50 sound tokens distributed over five categories (animal, human nonspeech, mechanical/alerting, nature, and musical instruments). Both closed-set (category identification) and open-set (token identification) nonlinguistic sound perceptions were examined. Twenty-two postlingually deafened CI users (mean age, 59.4 +/- 10 yrs) were evaluated using common speech perception test measures (Hearing In Noise test and Consonant-Nucleus-Consonant words) and the NLST following a pilot study in which nonlinguistic sound tokens used were selected or eliminated. RESULTS: The NLST was easily administered to all 22 CI subjects. An overall token identification score of 49 +/- 13.5% correct was obtained across all five categories. CI users were able to identify the correct category for 71 +/- 11.5% of tokens. A moderate correlation between speech perception and accuracy of nonlinguistic identification was found (r = 0.519, p = 0.016). CONCLUSIONS: The results suggest that nonlinguistic sounds are difficult for CI users to perceive. The categorization and identification scores suggest that sounds with harmonic structure or sounds with repetitive temporal structure are easier for CI users to perceive. A further developed clinical version of the NLST may be a useful clinical test to measure CI performance and progress, and perception of nonlinguistic sounds should receive greater attention during postimplant auditory rehabilitation. PMID- 20588117 TI - Neuroanatomical characteristics and speech perception in noise in older adults. AB - OBJECTIVES: Previous research has attributed older adults' difficulty with perceiving speech in noise to peripheral hearing loss. However, recent studies have suggested a more complex picture and implicate the central nervous system in sensation and sensory deficits. This study examines the relationship between the neuroanatomical structure of cognitive brain regions and the ability to perceive speech in noise in older adults. In particular, the neuroanatomical characteristics of the left ventral and dorsal prefrontal cortex (PFC) are considered relative to standard measures of hearing in noise. DESIGN: The participants were 15 older and 14 younger right-handed native speakers of American English who had no neurologic deficits and scored better than normal on standardized cognitive tests. We measured the participants' peripheral hearing ability and their ability to perceive speech in noise using established tests. Anatomical magnetic resonance images were taken and analyzed to extract regional volumes and thicknesses of several key neuroanatomical structures. RESULTS: Younger adults had better hearing sensitivity and better speech perception in noise ability than older adults. For the older adults only, the volume of the left pars triangularis and the cortical thickness of the left superior frontal gyrus were significant predictors of performance on the speech in noise test. DISCUSSION: These findings suggest that, in addition to peripheral structures, the central nervous system also contributes to the ability to perceive speech in noise. In older adults, a decline in the relative volume and cortical thickness of the PFC during aging can therefore be a factor in a declining ability to perceive speech in a naturalistic environment. These findings are consistent with the decline-compensation hypothesis, which states that a decline in sensory processing caused by cognitive aging can be accompanied by an increase in the recruitment of more general cognitive areas as a means of compensation. We found that a larger PFC volume may compensate for declining peripheral hearing. Clinically, recognizing the contribution of the cerebral cortex expands treatment possibilities for hearing loss in older adults beyond peripheral hearing aids to include strategies for improving cognitive function. We conclude by considering several mechanisms by which the PFC may facilitate speech perception in noise, including inhibitory control, attention, cross-modal compensation, word prediction and phonological working memory, although no definitive conclusion can be drawn. PMID- 20588120 TI - Application of the kurtosis statistic to the evaluation of the risk of hearing loss in workers exposed to high-level complex noise. AB - OBJECTIVE: Develop dose-response relations for two groups of industrial workers exposed to Gaussian or non-Gaussian (complex) types of continuous noises and to investigate what role, if any, the kurtosis statistic can play in the evaluation of industrial noise-induced hearing loss (NIHL). DESIGN: Audiometric and noise exposure data were acquired on a population (N = 195) of screened workers from a textile manufacturing plant and a metal fabrication facility located in Henan province of China. Thirty-two of the subjects were exposed to non-Gaussian (non G) noise and 163 were exposed to a Gaussian (G) continuous noise. Each subject was given a general physical and an otologic examination. Hearing threshold levels (0.5-8.0 kHz) were age adjusted (ISI-1999) and the prevalence of NIHL at 3, 4, or 6 kHz was determined. The kurtosis metric, which is sensitive to the peak and temporal characteristics of a noise, was introduced into the calculation of the cumulative noise exposure metric. Using the prevalence of hearing loss and the cumulative noise exposure metric, a dose-response relation for the G and non G noise-exposed groups was constructed. RESULTS: An analysis of the noise environments in the two plants showed that the noise exposures in the textile plant were of a Gaussian type with an Leq(A)8hr that varied from 96 to 105 dB whereas the exposures in the metal fabrication facility with an Leq(A)8hr = 95 dB were of a non-G type containing high levels (up to 125 dB peak SPL) of impact noise. The kurtosis statistic was used to quantify the deviation of the non-G noise environment from the Gaussian. The dose-response relation for the non-G noise-exposed subjects showed a higher prevalence of hearing loss for a comparable cumulative noise exposure than did the G noise-exposed subjects. By introducing the kurtosis variable into the temporal component of the cumulative noise exposure calculation, the two dose-response curves could be made to overlap, essentially yielding an equivalent noise-induced effect for the two study groups. CONCLUSIONS: For the same exposure level, the prevalence of NIHL is greater in workers exposed to non-G noise environments than for workers exposed to G noise. The kurtosis metric may be a reasonable candidate for use in modifying exposure level calculations that are used to estimate the risk of NIHL from any type of noise exposure environment. However, studies involving a large number of workers with well-documented exposures are needed before a relation between a metric such as the kurtosis and the risk of hearing loss can be refined. PMID- 20588121 TI - Children With Cochlear implants recognize their mother's voice. AB - OBJECTIVES: The available research indicates that cochlear implant (CI) users have difficulty in differentiating talkers, especially those of the same gender. The goal of this study was to determine whether child CI users could differentiate talkers under favorable stimulus and task conditions. We predicted that the use of a highly familiar voice, full sentences, and a game-like task with feedback would lead to higher performance levels than those achieved in previous studies of talker identification in CI users. DESIGN: In experiment 1, 21 CI users aged 4.8 to 14.3 yrs and 16 normal-hearing (NH) 5-yr-old children were required to differentiate their mother's scripted utterances from those of an unfamiliar man, woman, and girl in a four-alternative forced-choice task with feedback. In one condition, the utterances incorporated natural prosodic variations. In another condition, nonmaternal talkers imitated the prosody of each maternal utterance. In experiment 2, 19 of the child CI users and 11 of the NH children from experiment 1 returned on a subsequent occasion to participate in a task that required them to differentiate their mother's utterances from those of unfamiliar women in a two-alternative forced-choice task with feedback. Again, one condition had natural prosodic variations and another had maternal imitations. RESULTS: Child CI users in experiment 1 succeeded in differentiating their mother's utterances from those of a man, woman, and girl. Their performance was poorer than the performance of younger NH children, which was at ceiling. Child CI users' performance was better in the context of natural prosodic variations than in the context of imitations of maternal prosody. Child CI users in experiment 2 differentiated their mother's utterances from that of other women, and they also performed better on naturally varying samples than on imitations. CONCLUSIONS: We attribute child CI users' success on talker differentiation, even on same-gender differentiation, to their use of two types of temporal cues: variations in consonant and vowel articulation and variations in speaking rate. Moreover, we contend that child CI users' differentiation of speakers was facilitated by long-term familiarity with their mother's voice. PMID- 20588124 TI - Interesting times. PMID- 20588122 TI - Reliability of categorical loudness scaling and its relation to threshold. AB - OBJECTIVE: To further examine the reliability of categorical loudness scaling (CLS) for individual loudness categories and for the slope of the CLS functions. And, to evaluate the relationship between CLS and audiometric threshold. DESIGN: CLS functions were obtained in 74 subjects, 58 with hearing loss and 16 with normal hearing. CLS functions were measured at three frequencies (1, 2, and 4 kHz) in two separate sessions separated by as little as 1 wk and as much as 6 mo. Reliability of mean and median levels within each loudness category was assessed using SDs and correlation coefficients. Lines were fit to the CLS functions, and slopes of the lines were used to assess reliability and the relation between CLS and audiometric threshold. RESULTS: Similar reliability for CLS measurements was observed in both normal-hearing and hearing-impaired subjects at all frequencies. Across both groups of subjects, correlations describing the reliability of mean stimulus level within category exceeded 0.92 at all frequencies. In addition, SDs of the mean stimulus-level difference between visits ranged from 6.6 to 7.8 dB, depending on frequency. The correlation between the slope of a straight line fitted to the entire CLS function and audiometric threshold collapsed across frequencies was 0.72. Two line segments were then fit to the CLS function: one segment was fit to the soft portion of the CLS function (categorical units < or =20) and the other segment to the loud portion (categorical unit >20). Slopes of the line fit to the entire CLS function and of the line fit to the soft portion of the CLS function were both reliable across sessions. The slope of the line fit to the soft portion increased as audiometric threshold increased, with the correlations greater than 0.86 at all frequencies. No relationship was observed between slope of the line fit to the loud portion of the CLS function and audiometric threshold. Iso-loudness contours were constructed from the CLS data and used to determine the gain that would be needed to produce "normal" loudness percepts for hearing-impaired individuals. CONCLUSIONS: Within-subject CLS measurements were reliable across sessions both for individual loudness categories and for slope of the CLS functions. In addition, the slope of the low level portion of the CLS function varied in a predictable manner with audiometric threshold, with slope increasing as audiometric threshold increased. Finally, gain as a function of input level needed to provide loudness percepts for individuals with hearing loss equal to the loudness percepts of normal-hearing individuals can be estimated from audiometric threshold. This finding supports the assumption that audiometric threshold and response growth (loudness) are both determined by the same underlying cochlear mechanisms. PMID- 20588125 TI - Nearly fatal metabolic acidosis: septic or toxic? PMID- 20588126 TI - Health choices and heightened awareness: the art of the nudge! PMID- 20588127 TI - Using loving relationships to transform health care: a practical approach. AB - Several models of care that are based on quality, loving relationship are explicated that can enhance nursing work environments. Measurable improvements in quality of care for patients and quality of life for healthcare professionals can be derived by applying these practical approaches. PMID- 20588128 TI - Animal-facilitated therapy in various patient populations: systematic literature review. AB - With a soaring trend of the incorporation of complementary therapies into the mainstream of health care, animal-facilitated therapy has become a popular interest for the health care team to integrate into a patient's plan of care. This systematic literature summarizes the current research on the use of animal therapy in several patient populations and provides nursing implications for practice. PMID- 20588129 TI - The concept of health literacy within the older adult population. AB - Health literacy is a relatively new concept that has been evolving at a rapid pace over the past decade. As recently as 2004, nursing researchers were contributing only a small portion of the existing body of knowledge as it related to the concept of health literacy. But in the last 4 to 5 years, this trend has changed. More interest demonstrated by nursing scholars has caused an exponential increase in the literature being produced. The research to date has shown a direct correlation between low health literacy and poor health. Older adults have been identified as a vulnerable population with an estimated two-thirds of US adults aged 60 and older having inadequate or marginal literacy skills. A concept analysis of health literacy in the older adult population is warranted at this time to further clarify the concept and provide standard terminology and definitions for future holistic nursing practice and research, leading to better identification of health-literacy deficits and intervention within vulnerable populations. PMID- 20588130 TI - A pilot study to assess the effects of a guided imagery audiotape intervention on psychological outcomes in patients undergoing coronary artery bypass graft surgery. AB - Depression and anxiety are associated with increased risk of postoperative cardiac events and death in patients who have undergone coronary artery bypass graft surgery. These risks persist even several months after the procedure. Guided imagery has been used with cardiac surgery patients for some time and with numerous anecdotal reports of considerable benefit. In addition, this therapy is low-cost and easy to implement, and the literature holds ample evidence for its efficacy in symptom reduction in various patient populations. It was thus hypothesized that preoperative use of guided imagery would reduce postoperative distress in patients undergoing coronary artery bypass graft. Fifty-six patients scheduled to undergo coronary artery bypass graft at Columbia University Medical Center were randomized into 3 groups: guided imagery, music therapy, and standard care control. Patients in the imagery and music groups listened to audiotapes preoperatively and intraoperatively. All patients completed psychological, complementary medicine therapies use, and other assessments preoperatively and at 1 week and 6 months postoperatively. Only preoperative distress was predictive of postoperative distress at follow-up. Use of complementary medicine therapies was high in all groups and this fact, in addition to the small sample size, may have accounted for the lack of significant relationship between imagery and postoperative distress. Regardless, this complementary and alternative medicine therapy remains palatable to patients. Given its efficacy in other patient populations, it is worth exploring its potential utility for this population with a larger sample. PMID- 20588131 TI - Fish oil supplementation for management of dyslipidemia. AB - The use of herbal and natural remedies to prevent and manage disease is increasing in popularity. Individuals are attracted to the nonsynthetic qualities, affordability, and purity of natural remedies as compared to standard pharmacological and invasive interventions. Fish oil supplementation, for example, has been used in the management of dyslipidemia in patients choosing a natural approach to treatment or in adjunct to prescribed medication regimens. Research studies have supported the use of fish oil supplementation to reduce elevated levels of triglycerides and increase healthy cholesterol levels, as well as reduce the risk factors for cardiovascular disease. In this article, the use of fish oil supplementation to manage dyslipidemia will be explored, and considerations for this therapy for health care providers will be discussed. PMID- 20588132 TI - Spiritual practices in self-management of diabetes in African Americans. AB - In this qualitative study, African Americans described 3 orientations about spiritual practices and diabetes self-management: Spiritual practice as effort toward self-management; spiritual practice and self-management as effort toward healing; and spiritual practice as effort toward healing. Spiritual practices may influence diabetes self-management in African Americans and be a resource in care. PMID- 20588133 TI - Sweet dreams... PMID- 20588135 TI - Unloading therapy by intravenous diuretic in chronic heart failure: a double edged weapon? AB - A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness. PMID- 20588136 TI - Predictive value of cardiac troponin-I compared to creatine kinase-myocardial band for the assessment of infarct size as measured by cardiac magnetic resonance. AB - BACKGROUND: The estimation of infarct size by biochemical myocardial necrosis markers is used in current clinical practice, rather than the more expensive and not always available imaging techniques. However, for this purpose, the peak value of serum biomarkers can overestimate the necrotic area, especially after reperfusion. OBJECTIVE: We investigated whether late release cardiac troponin I (cTnI) values could predict more precisely infarct volume measured by delayed enhancement cardiac magnetic resonance (DE-CMR) in patients with acute myocardial infarction [ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI)] independently of reperfusion (spontaneous and provoked). METHODS: Sixty patients with a first acute myocardial infarction (55 STEMI and five NSTEMI) and normal function were enrolled. Among STEMI patients, 52 underwent reperfusion. cTnI and creatine kinase-myocardial band were assessed at admission and at 6, 12, 24, 48, 72 and 96 h (+/-1 h) from symptom onset. DE-CMR (Siemens Avanto 1.5T) was performed before discharge (4 +/- 2 days). Infarct size was determined by manual delineation of the areas of delayed enhancement. Infarct volume was calculated as the sum of each slice of infarct size area multiplied by thickness. RESULTS: Peak cTnI was 55 +/- 59 ng/ml (range 0.3-347). The area under the curve of cTnI was 1916 +/- 2224 ng/ml. The volume of infarcted myocardium assessed by DE-CMR was 27 +/- 25 ml (range 0-134). The single value of cTnI at 72 h after symptom onset provided the most accurate estimation of predischarge infarct volume (r = 0.84, 95% confidence interval 0.75-0.91) and was significantly more accurate than creatine kinase-myocardial band value assessed at any time during the same period (r = 0.42, 95% confidence interval 0.19-0.62; P < 0.002). CONCLUSION: In patients with a first acute myocardial infarction, cTnI value assessed at 72 h from symptom onset shows the best correlation with predischarge infarct volume as assessed by DE-CMR and is superior to cTnI and creatine kinase-myocardial band peak and total values. PMID- 20588139 TI - Applying Lean Six Sigma methodologies to improve efficiency, timeliness of care, and quality of care in an internal medicine residency clinic. AB - OBJECTIVE: Patients' connectedness to their providers has been shown to influence the success of preventive health and disease management programs. Lean Six Sigma methodologies were employed to study workflow processes, patient-physician familiarity, and appointment compliance to improve continuity of care in an internal medicine residency clinic. METHODS: We used a rapid-cycle test to evaluate proposed improvements to the baseline-identified factors impeding efficient clinic visits. Time-study, no-show, and patient-physician familiarity data were collected to evaluate the effect of interventions to improve clinic efficiency and continuity of medical care. RESULTS: Forty-seven patients were seen in each of the intervention and control groups. The wait duration between the end of triage and the resident-patient encounter was statistically shorter for the intervention group. Trends toward shorter wait times for medical assistant triage and total encounter were also seen in the intervention group. On all measures of connectedness, both the physicians and patients in the intervention group showed a statistically significant increased familiarity with each other. CONCLUSION: This study shows that incremental changes in workflow processes in a residency clinic can have a significant impact on practice efficiency and adherence to scheduled visits for preventive health care and chronic disease management. This project used a structured "Plan-Do-Study-Act" approach. PMID- 20588140 TI - Assessing the evidence of Six Sigma and Lean in the health care industry. AB - BACKGROUND: Popular quality improvement tools such as Six Sigma and Lean Systems (SS/L) claim to provide health care managers the opportunity to improve health care quality on the basis of sound methodology and data. However, it is unclear whether these 2 quality improvement tools actually improve health care quality. METHODS: The authors conducted a comprehensive literature review to assess the empirical evidence relating SS/L to improved clinical outcomes, processes of care, and financial performance of health care organizations. RESULTS: The authors identified 177 articles on SS/L published in the last 10 years. However, only 34 of them reported any outcomes of the SS/L projects studied, and less than one-third of these articles included statistical analyses to test for significant changes in outcomes. CONCLUSIONS: This review demonstrates that there are significant gaps in the SS/L health care quality improvement literature and very weak evidence that SS/L improve health care quality. PMID- 20588141 TI - Using in situ simulation to identify and resolve latent environmental threats to patient safety: case study involving operational changes in a labor and delivery ward. AB - Since the publication of "To Err Is Human" in 1999, health care professionals have looked to high-reliability industries such as aviation for guidance on improving system safety. One of the most widely adopted aviation-derived approaches is simulation-based team training, also known as crew resource management training. In the health care domain, crew resource management training often takes place in custom-built simulation laboratories that are designed to replicate operating rooms or labor and delivery rooms. Unlike these traditional crew resource management training programs, "in situ simulation" occurs on actual patient care units, involves actual health care team members, and uses actual organization processes to train and assess team performance. During the past 24 months, our research team has conducted nearly 40 in situ simulations. In this article, we present the results from 1 such simulation: a patient who experienced a difficult labor that resulted in an emergency caesarian section and hysterectomy. During the simulation, a number of latent environmental threats to safety were identified. This article presents the latent threats and the steps that the hospital has taken to remedy them. PMID- 20588142 TI - A physician leadership development program at an academic medical center. AB - To achieve care integration required for efficient high-quality care, physicians are increasingly organized into large multispecialty groups. The success of these groups depends in large part on the ability of leadership to successfully navigate the shifting reimbursement, regulatory, and quality and safety terrain, while simultaneously providing their physicians with a rewarding practice environment. The knowledge and management tools required for such leadership are not taught in medical school or residency and are rarely acquired as a product of day-to-day physician activities. In an effort to meet these challenges, the Massachusetts General Physicians Organization created a leadership development program. This article details the development, implementation, and experience of the program. PMID- 20588143 TI - The impact of information technology and organizational focus on the visibility of patient care errors. AB - INVESTIGATED: The implementation of information systems and the creation of an open culture, characterized by emphasis on patient safety and problem solving, are 2 means suggested to improve health care quality. This study examines the effects of use of information technology and focus on patient safety and problem solving on the visibility of patient care errors. SUBJECTS AND METHODS: A survey of nurses in Saudi Arabia is analyzed by means of factor analysis and multiregression analysis to examine nurses' use of information technology and culture in controlling errors. RESULTS AND CONCLUSIONS: Our research suggests that greater use of information technology to control patient care errors may reduce the prevalence of such errors while an increased focus on patient safety and problem solving facilitates an open environment where errors can be more openly discussed and addressed. The use of technology appears to have a role in decreasing errors. Yet, an organization that focuses on problem solving and patient safety can open lines of communication and create a culture in which errors can be discussed and resolved. PMID- 20588144 TI - Risk-adjusted indices for measuring the quality of inpatient care. AB - This article describes a risk-adjustment method for profiling hospitals and physicians on key measures of clinical quality using readily available administrative data. By comparing actual and expected rates of mortality, complications, readmissions, and patient safety events, this method enables providers to identify both favorable and adverse outcomes performance. PMID- 20588147 TI - Tackling the technical challenges that hinder the success of facet joint radiofrequency treatment for spinal pain. PMID- 20588148 TI - Toward a potential paradigm shift for the clinical care of diabetic patients requiring perineural analgesia: strategies for using the diabetic rodent model. PMID- 20588149 TI - Epidural hydromorphone: a step closer to the view from the top. PMID- 20588150 TI - Ultrasound guidance and peripheral nerve injury: is our vision as sharp as we think it is? PMID- 20588151 TI - Intravenous lidocaine is as effective as epidural bupivacaine in reducing ileus duration, hospital stay, and pain after open colon resection: a randomized clinical trial. AB - BACKGROUND: Both postoperative epidural analgesia and intravenous (IV) infusion of local anesthetic have been shown to shorten ileus duration and hospital stay after colon surgery when compared with the use of systemic narcotics alone. However, they have not been compared directly with each other. METHODS: Prospective, randomized clinical trial was conducted comparing the 2 treatments in open colon surgery patients. Before induction of general anesthesia, patients were randomized either to epidural analgesia (bupivacaine 0.125% and hydromorphone 6 microg/mL were started at 10 mL/hr within 1 hr of the end of surgery) or IV lidocaine (1 mg/min in patients < 70 kg, 2 mg/min in patients > or = 70 kg). Markers of return of bowel function, length of stay, postoperative pain scores, systemic analgesic requirements, and adverse events were recorded and compared between the 2 groups in an intent-to-treat analysis. RESULTS: Study enrollment took place from April 2005 to July 2006. Twenty-two patients were randomized to IV lidocaine therapy and 20 patients to epidural therapy. No statistically significant differences were found between groups in time to return of bowel function or hospital length of stay. The median pain score difference was not statistically significant. No statistically significant differences were found in pain scores for any specific postoperative day or in analgesic consumption. CONCLUSIONS: No differences were observed between groups in terms of return of bowel function, duration of hospital stay, and postoperative pain control, suggesting that IV infusion of local anesthetic may be an effective alternative to epidural therapy in patients in whom epidural anesthesia is contraindicated or not desired. PMID- 20588153 TI - The most recent recommendations for "deep blocks" and thromboprophylaxis: evidence not supporting a "thromboprophylaxis therapeutic window". PMID- 20588154 TI - The Houdini clavicle: arm abduction and needle insertion site adjustment improves needle visibility for the infraclavicular nerve block. PMID- 20588155 TI - Transversus abdominis plane block in lower segment cesarean section: a question of block failure or lack of efficacy? PMID- 20588156 TI - Hyperviscosity of the blood and epidural hematoma. PMID- 20588157 TI - Duplication of the brachial plexus: an ultrasound refraction artifact? PMID- 20588158 TI - Epigenetic regulation of telomerase expression in HIV-1-specific CD8+ T cells. AB - Telomerase activity in HIV-1-specific CD8(+) T cells from controllers contributes to the maintenance of highly functional cytotoxic T cell responses against HIV-1. Here, we show that high expression of telomerase in controllers is associated with hypermethylation at the distal and hypomethylation at the proximal human telomerase catalytic subunit promoter, whereas HIV-1-specific CD8(+) T cells from progressors showed an inverse pattern with distal promoter hypomethylation and proximal promoter hypermethylation. These data suggest distinct epigenetic signatures in HIV-1-specific T cells in progressors and controllers. PMID- 20588159 TI - HLA-G*0105N allele is associated with augmented risk for HIV infection in white female patients. AB - We analyzed HLA-G 3777G > C, HLA-G 14 bp deletion/insertion and HLA-G*0105N polymorphisms in HIV-positive white adult participants, infected through horizontal heterosexual transmission, and unexposed uninfected individuals, all from north eastern Italy. We report a new association between the HLA-G*0105N allele and HIV infection in adult white female participants, being HLA-G*0105N null allele correlated with an augmented risk (odds ratio = 4.35, 95% confidence interval = 1.38-18.07, P = 0.005) for HIV infection. PMID- 20588160 TI - The impact of active HIV-1 replication on the physiological age-related decline of immature-transitional B-cells in HIV-1 infected children. AB - OBJECTIVE: To characterize the level of immature-transitional B-cells in blood during pediatric HIV-1 infection in relation to active or suppressed viremia. We also aimed at characterizing the level of expression of CXCR4, CXCR5 and CCR7 on immature-transitional B-cells, as these receptors are important mediators for homing of B-cells. DESIGN: Forty-eight HIV-1 vertically infected children (33 viral controllers and 15 viremic patients) and 33 age-matched healthy controls were enrolled in a cross-sectional study. METHODS: We measured the levels of peripheral immature-transitional B-cells in all groups in relation to switched memory B-cells by flow cytometry. In parallel we evaluated CXCR4, CXCR5 and CCR7 expression on immature-transitional B-cells and measured plasma levels of CXCL12, BAFF and interleukin-7 by ELISA. RESULTS: We observed a lack of physiological age related decline of immature-transitional B-cells in viremic children in parallel to a decreased level of switched memory B-cells. Interestingly, immature transitional B-cells from viremic children presented with high levels of CXCR4. On the contrary, the level of CXCL12, the natural ligand for CXCR4, was lowest in the HIV-1 infected group, as compared with controls. CONCLUSION: Control of HIV-1 viremia through antiretroviral treatment appears to be crucial in decreasing the expansion and alteration of immature-transitional B-cells. PMID- 20588161 TI - Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AB - OBJECTIVE(S): To identify factors (including exposure to specific antiretroviral drugs) associated with severe vitamin D deficiency (VDD) in HIV-infected individuals and to explore the effects of severe VDD and antiretroviral drug exposure on serum alkaline phosphatase (ALP) as surrogate marker of bone turnover. DESIGN: Cross-sectional survey of vitamin D status among HIV-infected patients attending for routine clinical care at a large London HIV clinic. METHODS: Severe VDD was defined as 25(OH)D levels of less than 10 microg/l (<25 nmol/l). Multivariate logistic regression analysis was used to identify factors associated with severe VDD and upper quartile ALP levels. RESULTS: Vitamin D levels were measured in 1077 patients and found to be suboptimal in 91%. One third of patients had severe VDD. Black ethnicity, sampling in winter, nadir CD4 cell count less than 200 cells/microl, and exposure to combination antiretroviral therapy were associated with severe VDD. In analyses restricted to patients on combination antiretroviral therapy, current efavirenz use was significantly associated with severe VDD [adjusted odds ratio 2.0 (95% confidence interval 1.5 2.7)]. Current tenofovir [adjusted odds ratio 3.5 (95% confidence interval 2.3 5.2)] and efavirenz use [adjusted odds ratio 1.6 (95% confidence interval 1.02 2.4)], but not severe VDD [odds ratio 1.1 (0.8-1.5)], were associated with increased bone turnover (upper quartile ALP). CONCLUSION: Efavirenz was associated with severe VDD, a condition associated with multiple adverse health outcomes, and efavirenz and tenofovir with increased ALP. The clinical significance of these findings requires further investigation, given the widespread use of efavirenz and tenofovir in first-line combination antiretroviral therapy. PMID- 20588162 TI - Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients. AB - OBJECTIVE: The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. METHODS: Tonsillar biopsies were performed in seven antiretroviral naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. RESULTS: Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P < 0.001). Patients with greater collagen deposition showed lower levels of CD4 cells in lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P < 0.0001), treated patients with detectable lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). CONCLUSION: Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue. PMID- 20588163 TI - Increased levels of immune activation in the genital tract of healthy young women from sub-Saharan Africa. AB - OBJECTIVES: To determine whether healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4 T cells) than a similar population in the United States. DESIGN: A cross-sectional study nested in a phase 1 microbicide trial. METHODS: Cervical cytobrushes were collected from 18 to 24-year-old women in San Francisco, California, USA (n = 18) and Kisumu, Kenya (n = 36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, herpes simplex virus 2, gonorrhea, chlamydia, and trichomonas, and had abstained from sex for at least 7 days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. Secretory leukocyte protease inhibitor levels were assayed in cervicovaginal lavage samples. The Wilcoxon rank-sum test was used to compare immune parameters between sites. RESULTS: The total number of endocervical CD4(+) T cells was slightly higher in participants from San Francisco, but participants from Kisumu had a substantially higher number and proportion of CD4(+) T cells expressing the early activation marker CD69, with and without the HIV coreceptor C-C chemokine receptor type 5, and a greater proportion of activated CD8(+) T cells. Median (interquartile range) genital levels of secretory leukocyte protease inhibitor were lower in participants from Kisumu compared with those from San Francisco [190 (96-519) vs. 474 (206 817) pg/ml, P < 0.03]. CONCLUSION: Activated mucosal T cells were increased in the genital tract of young, sexually transmitted infection/HIV-free Kenyan women, independent of common genital coinfections, and secretory leukocyte protease inhibitor levels were reduced. The cause of these mucosal immune differences is not known, but could partly explain the high HIV incidence in young women from sub-Saharan Africa. PMID- 20588165 TI - Tuberculosis and HIV: danse macabre. PMID- 20588164 TI - HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection. AB - OBJECTIVE: HLA class I polymorphism is known to affect the rate of progression to AIDS after infection with HIV-1. Here we test the consistency of HLA-B allelic effects on progression to AIDS, heterosexual HIV transmission, and 'set point' viral levels. METHODS: We used adjusted Cox proportional hazard models in previously published relative hazard values for the effect of HLA-B alleles on progression to AIDS (n = 1089). The transmission study included 303 HIV-1 infected men with hemophilia and their 323 female sex partners (Multicenter Hemophilia Cohort Study cohort). Among 259 HIV-1 seroconverters (Multicenter AIDS Cohort Study cohort), HIV RNA levels at 'set point' were determined in stored plasma samples by a reverse-transcription polymerase chain reaction assay. HLA-B genotyping was performed by sequence-specific oligonucleotide hybridization and DNA sequencing. RESULTS: Several HLA-B alleles showed consistent associations for AIDS risk, infectivity, and 'set point' HIV RNA. HLA-B*35 was associated with more rapid progression to AIDS (relative hazard 1.39; P = 0.008), greater infectivity (odds ratio 3.14; P = 0.002), and higher HIV RNA (P = 0.01), whereas the presence of either B*27 or B*57 associated with slower progression to AIDS (B*27: relative hazard 0.49, P < 0.001; B*57: relative hazard 0.40, P < 0.0001), less infectivity (odds ratio 0.22 and 0.31, respectively, though not significant), and lower viral levels (P < 0.0001). Importantly, HLA-B polymorphism in female partners was not associated with susceptibility to HIV-1 infection. CONCLUSION: HLA-B polymorphisms that affect the risk of AIDS may also alter HIV-1 infectivity, probably through the common mechanism of viral control, but they do not appear to protect against infection in our cohort. PMID- 20588167 TI - Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AB - Epicardial fat accumulation may have important clinical consequences, yet little is known regarding this depot in HIV patients. We compared epicardial fat volume in 78 HIV-infected men and 32 HIV-negative controls. Epicardial fat volume was higher in HIV-infected patients than that in controls (P = 0.04). In HIV patients, epicardial fat volume was strongly associated with visceral adipose tissue area (rho = 0.76, P < 0.0001), fasting glucose (rho = 0.41, P = 0.001) and insulin (rho = 0.44, P = 0.0003). Relationships with glucose and insulin remained significant controlling for age, race, BMI, adiponectin, visceral adipose tissue and antiretroviral therapy. Epicardial fat may be an important fat depot in HIV infected patients. PMID- 20588168 TI - The cytotoxic lymphocyte antigen 4 polymorphisms affect response to hepatitis C virus-specific therapy in HIV(+) patients with acute and chronic hepatitis C virus co-infection. AB - OBJECTIVE: Cytotoxic lymphocyte antigen 4 (CTLA4), a co-receptor expressed on T lymphocytes, is involved in the regulation of T-cell functions. Here, we analyzed the potential impact of the CTLA4 polymorphisms on response to hepatitis C virus (HCV)-specific treatment in HIV(+) patients co-infected with HCV. PATIENTS AND METHODS: A total of 184 HIV/HCV co-infected Caucasian patients were enrolled into this study, including 109 patients with chronic and 75 patients with acute hepatitis C. CTLA4 genotypes were determined by LightCycler PCR. RESULTS: We found the CTLA4 -318 C/C genotype to be associated with sustained virological response in HCV/HIV co-infection (P = 0.035). Moreover, response rates were significantly higher in patients with a +49G/G genotype [23/29 (79.3%)] than in carriers of other +49 genotypes [59/155 (38.1%); OR 6.2; P = 0.00005]. Of note, the CTLA4 +49G/G genotype was confirmed as an independent predictor for treatment response in both patients with acute and chronic hepatitis C. CONCLUSION: CTLA4 polymorphisms are associated with treatment-induced resolution of HCV infection in HIV co-infected patients. These findings underline the impact of genetic host factors for successful treatment. PMID- 20588166 TI - The effect of transmitted HIV-1 drug resistance on pre-therapy viral load. AB - BACKGROUND: Reduced replication capacity of viruses expressing drug resistant mutations implies that patients with transmitted drug resistance (TDR) could have lower HIV RNA viral load than those infected with wild-type virus. METHODS: We performed analysis using data from the UK HIV Drug Resistance Database and the UK CHIC study. Eligible patients had a resistance test performed between 1997 and 2007 while naive to antiretroviral therapy, were 16 years or older, and had a viral load and CD4 cell count measurement within 6 months of this test. Models were adjusted for CD4 cell count, viral subtype, ethnicity, risk group, sex, age, calendar year, clinical centre, and viral load assay. RESULTS: Of a total of 7994 patients included, 709 (9%) had TDR: 604 (85%) had resistance to one drug class only [350 nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 164 non nucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 90 protease inhibitors (PIs)], 77 (11%) to two classes (42 NRTIs/NNRTIs, 31 NRTIs/PIs, 4 NNRTIs/PIs), and 28 (4%) had resistance to all three classes. The overall mean (SD) viral load at the time of resistance testing was 4.60 (0.82) log(10) copies/ml, and did not differ by class of TDR. However, patients harbouring M184V/I (n = 61) had a significantly lower viral load [adjusted mean difference -0.33 log10 copies/ml (95% CI -0.54 to -0.11), 53% lower (95% CI 22 to 71%), P = 0.002] compared to wild-type virus. DISCUSSION: Our study provides clear evidence of an in-vivo fitness cost associated with the M184V/I mutation independent of drug effects which select for this mutation. This was not observed for any other mutation, but true effects may have been obscured by reversion of initially resistant viruses to wild-type. PMID- 20588169 TI - A TRIM5alpha exon 2 polymorphism is associated with protection from HIV-1 infection in the Pumwani sex worker cohort. AB - OBJECTIVE: The innate immune component TRIM5alpha has the ability to restrict retrovirus infection in a species-specific manner. TRIM5alpha of some primate species restricts infection by HIV-1, whereas human TRIM5alpha lacks this specificity. Previous studies have suggested that certain polymorphisms in human TRIM5alpha may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5alpha polymorphisms in resistance/susceptibility to HIV-1 within the Pumwani sex worker cohort in Nairobi, Kenya. A group of women within this cohort remain HIV-1-seronegative and PCR-negative despite repeated exposure to HIV-1 through active sex work. DESIGN: A 1 kb fragment of the TRIM5alpha gene, including exon 2, from 1032 women enrolled in the Pumwani sex worker cohort was amplified and sequenced. Single-nucleotide polymorphisms (SNPs) and haplotypes were compared between HIV-1-positive and resistant women. METHODS: The TRIM5alpha exon 2 genomic fragment was amplified, sequenced and genotyped. Pypop32-0.6.0 was used to determine SNP and haplotype frequencies and statistical analysis was carried out using SPSS-13.0 for Windows. RESULTS: A TRIM5alpha SNP (rs10838525) resulting in the amino acid change from arginine to glutamine at codon 136, was enriched in HIV-1-resistant individuals [P = 1.104E-05; odds ratio (OR) 2.991; 95% confidence interval (CI) 1.806-4.953] and women with 136Q were less likely to seroconvert (P = 0.002; log-rank 12.799). Wild-type TRIM5alpha exon 2 was associated with susceptibility to HIV-1 (P = 0.006; OR 0.279; 95% CI 0.105-0.740) and rapid seroconversion (P = 0.001; log-rank 14.475). CONCLUSIONS: Our findings suggest that a shift from arginine to glutamine at codon 136 in the coiled-coil region of TRIM5alpha confers protection against HIV-1 in the Pumwani sex worker cohort. PMID- 20588171 TI - Expanding access to HAART: a cost-effective approach for treating and preventing HIV. AB - OBJECTIVE: HIV continues to present a substantial global health burden. Given the high direct medical costs associated with the disease, prevention of new transmission is an important element in limiting economic burden. In addition to providing therapeutic benefit, treatment with HAART has potential to prevent transmission of HIV. The objective in this study was to perform an economic evaluation of the incremental net benefit associated with an intervention to expand treatment with HAART in British Columbia, Canada. DESIGN: A mathematical model describing transmission of HIV, integrated with a microsimulation model describing the clinical and economic course of HIV. METHODS: The primary outcome was the incremental net benefit of expanding treatment with HAART from 50 to 75% of clinically eligible individuals in British Columbia, assuming a willingness-to pay threshold of US$ 50,000 per quality-adjusted life year. Direct medical costs included were antiretroviral and nonantiretroviral medications, hospitalizations, physician visits, and laboratory tests. The mathematical and microsimulation models were based on patient characteristics observed in British Columbia. Longitudinal data described health services utilization, clinical progression, and survival for all individuals receiving treatment for HIV in British Columbia. RESULTS: Over 30 years, the HAART expansion scenario was associated with a net benefit of US$ 900 million (95% confidence interval US$ 493 million to 1.45 billion). CONCLUSION: Increasing the HAART treatment rate from 50 to 75% of clinically eligible individuals in British Columbia appears to be a cost effective strategy based on this model. These cost-effectiveness results are consistent with public health objectives: all individuals who are eligible for an established life-saving treatment should receive it. PMID- 20588170 TI - Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AB - OBJECTIVE: To investigate the relative predictive value of CD4(+) metrics for serious clinical endpoints. DESIGN: Observational. METHODS: Patients (3012; 20 317 person-years) from control arms of ESPRIT and SILCAAT were followed prospectively. We used Cox regression to identify CD4(+) metrics (latest, baseline and nadir CD4(+) cell count, latest CD4(+)%, time spent with CD4(+) count below certain thresholds and CD4(+) slopes) independently predictive of all cause mortality, non-AIDS deaths, non-AIDS (cardiovascular, hepatic, renal and non-AIDS malignancy) and AIDS events. Akaike information criteria (AIC) were calculated for each model. Significant metrics (P < 0.05) were then additionally adjusted for latest CD4(+) cell count. RESULTS: Non-AIDS deaths occurred at a higher rate than AIDS deaths [rate ratio: 6.48, 95% confidence interval (CI) 5.1 8.1], and non-AIDS events likewise (rate ratio: 1.72, 95% CI 1.65-1.79). Latest CD4(+) cell count was strongly predictive of lower risk of death (hazard ratio per log2 rise: 0.48, 95% CI 0.43-0.54), with lowest AIC of all metrics. CD4(+) slope over seven visits, after additional adjustment for latest CD4(+) cell count, was the only metric to be an independent predictor for all-cause (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 3.04, 95% CI 1.98-4.67) and non-AIDS deaths (hazard ratio for slope <-10 cells/microl per month vs. 0 +/- 10: 2.62, 95% CI 1.62-4.22). Latest CD4(+) cell count (per log(2) rise) was the best predictor across all four endpoints and predicted hepatic (hazard ratio 0.46, 95% CI 0.33-0.63) and renal events (hazard ratio 0.39, 95% CI 0.21-0.70), but not cardiovascular events (hazard ratio 1.05, 95% CI 0.77-1.43) or non-AIDS cancers (hazard ratio 0.78, 95% CI 0.59-1.03). CONCLUSION: Latest CD4(+) cell count is the best predictor of serious endpoints. CD4(+) slope independently predicts all-cause and non-AIDS deaths. PMID- 20588172 TI - Exposure to HIV-1-encoded Toll-like receptor 8 ligands enhances monocyte response to microbial encoded Toll-like receptor 2/4 ligands. AB - BACKGROUND: Chronic HIV-1 infection is characterized by high levels of persistent immune activation. Both HIV-1-encoded Toll-like receptor 7/8 (TLR7/8) ligands and TLR ligands encoded by products of microbial translocation have been implicated in inducing and sustaining immune activation in infected individuals, but the consequences of simultaneous exposure to different TLR ligands are not well understood. OBJECTIVE: To examine the impact of preexposure of monocytes to HIV-1 encoded TLR8 ligands on their ability to respond to subsequent stimulation with microbial TLR2/4 ligands. METHOD: Stable monocytic cell lines (THP-1-Blue-CD14 cells) or primary monocytes were stimulated with ligands for TLR2, TLR4, and TLR8, including chemically inactivated HIV-1, alone, or in sequential combinations. Responses by THP-1 cells to TLR stimulation were quantified using Quanti-Blue colometric assay, and TLR-induced tumor necrosis factor-alpha production of primary monocytes was quantified by intracellular cytokine staining using flow cytometry. RESULTS: The exposure of monocytes to HIV-1 or HIV-1 derived TLR8 ligands sensitized these cells for TLR4 stimulation, resulting in a significantly higher response to lipopolysaccharide compared to cells that were not prestimulated with TLR8 ligands or HIV-1. CONCLUSION: TLR crosstalk can enhance the pro-inflammatory monocytes response to products of microbial translocation and might play an important role in the modulation of immune function in HIV-1 infection. PMID- 20588173 TI - Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach. AB - OBJECTIVES: To identify biological factors associated with HIV transmission in men who have sex with men (MSM). DESIGN: A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data. METHODS: Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling. RESULTS: Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54-0.86], P=0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15-2.25), P=0.005], recent infection [rate ratio 3.88 (95% CI 1.76-8.55), P=0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51-11.29), P=0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07-0.27, P=0.0001). CONCLUSION: Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission. PMID- 20588174 TI - p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. AB - BACKGROUND: In the human papillomavirus (HPV) era, the best way to assess oropharyngeal squamous carcinomas (SCC) for risk stratification is not clear. Many recommend use of both p16 immunohistochemistry and HPV in situ hybridization (ISH). A significant minority of tumors are p16 positive and HPV ISH negative, the significance of which is unclear. METHODS: Two hundred thirty-nine oropharyngeal SCC were tested by immunohistochemistry for p16 and by ISH for high risk HPV. For p16 positive, HPV ISH negative cases, PCR was conducted for HPV. The findings were correlated with pathologic and clinical findings. RESULTS: Of the 239 cases, 187 (78%) were positive for p16. Of these, 139 (74%) were positive for HPV by ISH. Of the remaining 48 cases, 45 had material for PCR. Nineteen were positive for HPV, leaving a group of 26 p16 positive and HPV undetectable SCCs. In the p16 positive cohort, there was no difference in survival between HPV ISH positive and negative cases. Comparing the HPV ISH positive and HPV ISH and PCR negative SCC, there was again no difference in survival. p16 positive, HPV negative SCC still had significantly better survival than p16 negative SCC in univariate and multivariate analysis. CONCLUSIONS: Outcomes for p16 positive, HPV negative oropharyngeal SCC are not significantly different from p16 positive, HPV positive tumors and are significantly better than for p16 negative tumors. These results suggest that p16 immunohistochemistry alone is the best test to use for risk stratification in oropharyngeal SCC. PMID- 20588176 TI - Endometrial giant cell carcinoma: a case series and review of the spectrum of endometrial neoplasms containing giant cells. AB - Poorly differentiated endometrial carcinomas of specific type include the rarely reported endometrial carcinoma with a malignant giant cell component [endometrial giant cell carcinoma (GCC)]. Since the initial description in 1991, there has only been 1 subsequent case report of this entity. We report another 5 cases. The patients ranged in age from 53 to 83 years, presenting with vaginal bleeding, anemia, or a pelvic mass. Four of the 5 tumors contained areas of endometrial adenocarcinoma of usual type, with a variable giant cell component. The conventional cell types present included 1 case with clear cell carcinoma (30% of tumor volume), 2 with high-grade endometrioid carcinoma (50% and 70% of tumor volume, respectively) and 1 with serous histology (10% of tumor volume). One was composed exclusively of giant cell carcinoma. The giant cell component in all cases consisted of poorly cohesive nests of bizarre multinucleated giant cells with mononuclear tumor cells. A striking peritumoral and intratumoral inflammatory cell infiltrate composed of lymphocytes, plasma cells and focal eosinophils, and neutrophils was present and emperipolesis was noted in 4 of the 5 cases. The giant cells showed focal staining for epithelial markers (AE1/AE3 and CAM 5.2). Three of the patients presented with stage 1A disease, 1 with stage 1B disease, and 1 tumor was advanced, presenting as stage IIIC2. One patient in whom the tumor was exclusively of the giant cell type, developed lung metastasis 4 years after diagnosis and 1 patient is disease free after 14 years. The remaining 3 patients showed no evidence of disease with 15 to 32 months of follow up. As histotype supplemented by staging information is critical in selection of treatment modalities and in prognostication in uterine malignancies, accurate classification is mandated. Here, we present a series of endometrial carcinomas containing a component of GCC and discuss the spectrum of giant cell-containing uterine neoplasms. At this time, however, the cumulative data on endometrial GCC are limited and the prognostic significance of the presence and the extent of a giant cell component in endometrial carcinoma remains uncertain. PMID- 20588175 TI - NKX3.1 as a marker of prostatic origin in metastatic tumors. AB - NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma. This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined. Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6 mm tissue cores) of hormone naive metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. NKX3.1 seems to be a highly sensitive and specific tissue marker of metastatic prostatic adenocarcinoma. In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas. PMID- 20588177 TI - Dedifferentiated liposarcoma with "homologous" lipoblastic (pleomorphic liposarcoma-like) differentiation: clinicopathologic and molecular analysis of a series suggesting revised diagnostic criteria. AB - Dedifferentiated liposarcoma (LPS) is a malignant adipocytic neoplasm defined as the transition from well-differentiated LPS to a nonlipogenic sarcoma. Heterologous differentiation is seen in 5% to 10% of dedifferentiated LPS, usually with myogenic or osteo/chondrosarcomatous elements. Adipocytic differentiation in the dedifferentiated component is incompatible with the current definition of dedifferentiated LPS. Pleomorphic LPS is a high-grade sarcoma containing lipoblasts. At least in areas, pleomorphic LPS can be indistinguishable from dedifferentiated LPS, except for the presence of lipoblasts in pleomorphic LPS and well-differentiated LPS areas in dedifferentiated LPS. We evaluated 12 unusual liposarcomas: 11 cases with pleomorphic LPS-like morphology affecting patients with concomitant or previous well-differentiated/dedifferentiated LPS, and 1 case resembling inflammatory "MFH" with scattered lipoblasts. Clinical and histologic features were reviewed. Immunohistochemistry for MDM2 and CDK4 was carried out. Amplification of 12q13 to q15 was studied by FISH analysis of the HMGA2 locus. The tumors arose in the retroperitoneum (7), proximal lower extremity (3), chest wall (1), and neck (1) of 9 males and 3 females (median age 66 y; range 49 to 76). Size ranged from 9 to 32 cm (median 23 cm). In 3 cases, there was an abrupt transition between well differentiated LPS and sheets of pleomorphic lipoblasts, indistinguishable from pleomorphic LPS. Four cases consisted of otherwise typical dedifferentiated LPS (with adjacent well-differentiated LPS), except for the presence of lipoblasts in the high-grade component. One case contained both nonlipogenic spindle cell areas and an inflammatory "MFH"-like component with numerous admixed lipoblasts. Four cases were composed exclusively of pleomorphic LPS-like areas developing in 1 of the recurrences or metastases of a prior typical dedifferentiated LPS. Two cases also showed heterologous smooth muscle differentiation. MDM2 and CDK4 were positive in both the dedifferentiated LPS and pleomorphic LPS-like components in 12/12 and 11/12 cases, respectively. FISH analysis showed high-level amplification of 12q14.3 in all 8 cases successfully tested. Karyotypes were available for 3 cases and showed ring and giant marker chromosomes. Follow-up, available for 11 patients, ranged from 19 to 196 months (median 36 mo). Seven patients developed local recurrences (multiple in 3), and 3 developed lung metastases. Thus far, 5 patients have died of disease, 3 are alive with recurrent or metastatic disease, and 3 are alive with no evidence of disease. We conclude that dedifferentiated LPS can show lipoblastic differentiation in the high-grade component, resulting in areas indistinguishable from pleomorphic LPS. The available clinical and molecular data support the notion of "homologous" lipoblastic differentiation in dedifferentiated LPS, rather than mixed-type LPS. PMID- 20588178 TI - A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. AB - The MECT1/MAML2 translocation is identified in a large proportion of mucoepidermoid carcinomas (MEC) of the salivary gland and is an emerging favorable prognosticator. However, there are conflicting data on this translocation's specificity, restriction to low/intermediate MEC, and strength as a prognosticator. We present our experience with the MECT1/MAML2 translocation in a large cohort of MECs to address these issues. We analyzed 55 salivary MEC and 36 potential MEC mimics (24 Warthin tumors, 5 oncocytomas, 3 squamous cell carcinomas, 2 squamoid salivary duct carcinomas, 1 lymphoepithelial cyst, 1 Schneiderian carcinoma ex papilloma) for presence of the MECT1/MAML2 translocation by fluorescent in-situ hybridization (FISH) and real-time RT-PCR. Overall, MECT1/MAML2 translocation was present in 36/55 (66%) of MEC whereas all 36 non-MEC were negative for translocation. Low or intermediate-grade MEC had a higher frequency of translocation (75%) than high-grade MEC (46%) (P=0.039). Translocation positive cases had a better disease-specific survival (log rank P=0.026) although 2 patients still died of disease. Within high-grade MEC, MECT1/MAML2 positive tumors had lower rates of anaplasia (P=0.001), and mitotic counts (P=0.012). Thus, MECT1/MAML2 translocation is highly specific for MEC and imparts a better prognosis. However, it is frequent even within high-grade MEC and can be seen in lethal cases suggesting that translocation status should not supersede conventional parameters. There are 2 distinct subgroups within high grade MEC, and the translocation negative tumors may actually be more appropriately categorized as another tumor type (such as adenosquamous carcinoma). PMID- 20588179 TI - Bilirubin exerts renoprotective effects in angiotensin II-hypertension. AB - Bilirubin is an endogenous antioxidant and is the end product of heme catabolism by heme oxygenase (HO) and biliverdin reductase. Chronic angiotensin II (Ang II) infusion induces renal HO-1 expression that is associated with renoprotective effects, and further induction of renal HO-1 attenuates the development of hypertension in this model. To determine the effects of bilirubin on the development of Ang II-induced hypertension and resultant proteinuria, 2 groups of rats were studied: Ang II (n = 4) and Ang II + bilirubin (n = 4). Rats were infused with Ang II (80 ng/min for 2 weeks), and bilirubin was administered simultaneously in 1 group (3 mg/100 g body weight/48 hr, intraperitoneally). Two weeks after onset of Ang II infusion, systolic blood pressure significantly increased from 134 +/- 4 to 198 +/- 7 mm Hg (P < 0.05) in the Ang II group and from 128 +/- 8 to 209 +/- 9 mm Hg (P < 0.05) in the Ang II + bilirubin group. Relative to the Ang II group, treatment with bilirubin did not alter body weight, food intake, water intake or urine output. However, urinary protein excretion was significantly lower in the Ang II + bilirubin group (32.9 +/- 9.7 mg/d versus 81.4 +/- 22.8 mg/d, P < 0.05). The authors conclude that exogenous bilirubin exerts renoprotective effects in Ang II-dependent hypertension. PMID- 20588180 TI - Chyluria and delayed graft function in early posttransplant period in a renal transplant patient. AB - Chyluria mostly occurs because of the leakage of lymphatic fluid into the urinary system from the lymphatic system. The patient reported here with end-stage renal disease caused by the nephrotic syndrome underwent renal transplantation from a living donor. During the early posttransplant period, her daily urine output was 300 to 400 mL, and it was chylous. The only abnormality on physical examination was pretibial edema. On renal biopsy, there was no sign of glomerular disease, acute tubular necrosis, or rejection that could have caused delayed graft function. All factors except surgery were excluded, and a lymphourinary fistula was demonstrated with lymphoscintigraphy. After 15 days, chyluria resolved and she recovered spontaneously. Normal diuresis began, and her creatinine level decreased to less than 1 mg/dL in 3 days. According to our knowledge, this is the first chyluria case secondary to surgery in the posttransplant setting. PMID- 20588181 TI - Hepatotoxicity fears contribute to underutilization of statin medications by primary care physicians. AB - INTRODUCTION: The safety and efficacy of hydroxymethylglutaryl CoA reductase inhibitors (statins) have been extensively demonstrated, but in clinical practice, there remains significant underutilization of these medications. The authors hypothesized that this underutilization could stem in part from fear of liver damage caused by statins. The purpose was to determine whether concern about hepatotoxicity acts as a barrier among primary care physicians to prescribing statins for patients with elevated liver transaminase values and/or underlying liver disease. METHOD: The survey included 937 primary care physicians from 138 academic centers in the United States, and the following were measured: (1) comparison of statin prescribing for patients with clinical indications and (a) no mention of liver transaminase values, (b) elevated liver transaminase values and (c) underlying liver disease; (2) correlation between perception of statin hepatotoxicity and statin prescribing. RESULTS: Seventy-one percent of respondents would prescribe statins in scenario 1, (45-year-old woman with low density lipoprotein 240 mg/dL), whereas only 50% would prescribe statins if the baseline liver transaminase values were elevated to 1.5 times upper limit of normal (P < 0.001). This prescribing rate dropped even further to 40% in scenario 3 (55-year-old man with known coronary disease, low-density lipoprotein 250 mg/dL and hepatitis C). Thirty-seven percent of respondents had falsely elevated perceptions of statin hepatotoxicity risk, and these perceptions correlated inversely with statin prescribing. The method of survey administration prevented calculation of response rate, possibility of response bias exists. CONCLUSION: Despite extensive data documenting safety of statins, primary care physicians harbor significant hepatotoxicity concerns, and these concerns act as a barrier to statin utilization. PMID- 20588183 TI - Modeling physical activity outcomes: a two-part generalized-estimating-equations approach. AB - The health benefits of physical activity are well known. Various parameters of physical activity, such as time or energy expenditure, are often assessed in observational and experimental studies. This article highlights several methodologic issues concerning the analysis of physical activity. These include non-normality, presence of many zeros, and violation of the independence assumption. Application of the standard regression model to a (log-transformed) physical activity variable may lead to spurious associations and misleading conclusions. We developed an alternative 2-part generalized-estimating-equations (GEE) approach to analyze the heterogeneous and correlated physical activity data. We first estimated a logistic GEE model for the prevalence of physical activity and factors affecting physical activity participation. We then fit a gamma GEE model to assess the effects of predictors among persons engaging in physical activity. An empirical application to an epidemiologic study of physical activity of community-dwelling older adults illustrates the proposed methodology. PMID- 20588182 TI - Improved cardiac performance by rosuvastatin is associated with attenuations in both myocardial tumor necrosis factor-alpha and p38 MAP kinase activity in rats after myocardial infarction. AB - INTRODUCTION: Statins have been shown to exert anti-inflammatory effects. The aim of this study was to investigate whether rosuvastatin has favorable effect on ventricular remodeling after myocardial infarction (MI), whether this effect is associated with tumor necrosis factor (TNF)-alpha expression and p38 mitogen activated protein (MAP) kinase pathway and, furthermore, whether there is close correlation between gene expression of TNF-alpha and activity of p38 MAP kinase. METHODS AND RESULTS: Adult male Wistar rats with acute MI were randomly divided into 2 groups: (1) rosuvastatin-treated group (MI-R) receiving rosuvastatin 20 mg/kg once daily, and (2) infarcted group (MI) receiving saline, when compared with sham-operated control group. Four weeks later, echocardiography, hemodynamics and Van Gieson staining were applied to evaluate left ventricular remodeling and cardiac function. Myocardial gene expression of TNF-alpha and activity of p38 MAP kinase were analyzed by real time-polymerase chain reaction and Western blot, respectively. The results demonstrated that increased TNF-alpha gene expression in noninfarcted areas was accompanied by activation of p38 MAP kinase pathway. Moreover, treatment of rosuvastatin markedly improved ventricular remodeling and cardiac function in rats, which was associated with attenuations in both TNF-alpha gene expression and p38 MAP kinase activity in myocardium without changes in serum lipid levels. CONCLUSIONS: Treatment of rosuvastatin was able to improve cardiac remodeling and cardiac function after acute MI, which was associated with attenuations in both expression of TNF-alpha and activity of p38 MAP kinase in myocardium. PMID- 20588184 TI - Considerations in using US-based laboratory toxicity tables to evaluate laboratory toxicities among healthy malawian and Ugandan infants. AB - OBJECTIVES: To determine normal hematologic and selected blood chemistry values among healthy, full-term, non-HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables. DESIGN: This was a cross-sectional laboratory study of infants from birth to 6 months of age. METHODS: Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables. RESULTS: In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms. CONCLUSIONS: These findings underscore the importance of establishing relevant local laboratory norms for infants. PMID- 20588186 TI - The role of microRNA in cardiac excitability. AB - Cardiomyocytes are excitable cells that can generate and propagate excitations; excitability is a fundamental characteristic of these cells, which is reflected by action potential; the changes of transmembrane potential as a function of time; and orchestrated by ion channels, transporters, and cellular proteins. The electrical excitation evoked in muscles must be transformed into mechanical contraction through the so-called excitation-contraction coupling mechanism, and the proper contraction of cardiac muscles then drives pumping of blood to the body circulation. Arrhythmias are electrical disturbances that can result in irregular heart beating with consequent insufficient pumping of blood. Arrhythmias are often lethal, constituting a major cause for cardiac death, particularly sudden cardiac death, in myocardial infarction and heart failure. Recent studies have led to discovery of microRNAs (miRNAs) as a new player in the cardiac excitability by fine-tuning expression of ion channels, transporters, and cellular proteins, which determines the arrhythmogenicity in many conditions. This review article will give a comprehensive summary on the data available in the literature. The basics of cardiac excitability will first be introduced, followed by a brief introduction to the basics of miRNAs. Then, studies on regulation of cardiac excitability by miRNAs will be described and analyzed. Finally, concluding remarks will be provided. PMID- 20588185 TI - Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa. AB - BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level. PMID- 20588187 TI - Standard versus low-dose transdermal nitroglycerin: differential effects on the development of tolerance and abnormalities of endothelial function. AB - We compared standard (0.6 mg/h) versus low-dose (0.05 mg/h) transdermal nitroglycerin (TGTN) on acute hemodynamic parameters, the development of tolerance, and endothelial function. Study 1 randomized six healthy volunteers to receive 0.6 mg/h or 0.05 mg/h TGTN in a crossover design study (6-day washout period) with measurements of heart rate, blood pressure, radial artery waveforms, and aortic augmentation index taken at baseline and 1, 2, and 3 hours after initial TGTN application. Study 2 enrolled 24 healthy volunteers to receive 400 MUg of sublingual nitroglycerin spray followed by 400 MUg of inhaled salbutamol 90 minutes later. Measurements of heart rate, blood pressure, radial artery waveforms as well as aortic augmentation index were taken at baseline and at 5, 10, and 20 minutes after each treatment. They were randomized to either 0.6 mg/h or 0.05 mg/h of TGTN, and the same measurements were repeated after 6 days. In Study 1, there was no significant difference in the response to both doses (analysis of variance, P < 0.05). In Study 2, the decrease in aortic augmentation index in response to sublingual nitroglycerin and salbutamol was attenuated after sustained therapy with 0.6 mg/h of TGTN (versus 0.05 mg/h, P < 0.05). This investigation documents that 0.05 mg/h TGTN has identical acute hemodynamic effects compared with 0.6-mg/h dose without causing tolerance or endothelial dysfunction. PMID- 20588188 TI - Cytochrome P450-derived epoxyeicosatrienoic acids and pulmonary hypertension: central role of transient receptor potential C6 channels. AB - Hypoxia induces the constriction of pulmonary resistance arteries, which results in the redistribution of blood from poor to better ventilated areas, thus optimizing its oxygenation. Many different oxygen-sensing mechanisms have been proposed to regulate this process, including cytochrome P450 enzymes. These enzymes, which convert substrates such as arachidonic acid into bioactive epoxides (the epoxyeicosatrienoic acids [EETs]), are highly expressed in the lung as is the soluble epoxide hydrolase which metabolizes the epoxides to their less active diols. The EETs play a well-documented role as endothelium-derived vasodilators in the systemic vasculature, but in the pulmonary circulation, they are generated in vascular smooth muscle cells and potentiate vasoconstriction. Preventing the breakdown of 11,12-EET by the inhibition or genetic deletion of the soluble epoxide hydrolase strongly augments the response to hypoxia. Mechanistically, 11,12-EET potentiates the contractile response by recruiting transient receptor potential C6 channels to caveolae. Indeed, neither 11,12-EET nor hypoxia is able to elicit pulmonary vasoconstriction in TRPC6 knockout mice. The cytochrome and soluble epoxide hydrolase enzymes are also implicated in the vascular remodeling associated with chronic hypoxia and pulmonary hypertension. Thus, targeting this pathway may be in an attractive new therapeutic approach to treat this incapacitating disease. PMID- 20588189 TI - A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter. AB - BACKGROUND: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. METHODS: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. RESULTS: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. CONCLUSIONS: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation. PMID- 20588191 TI - Ascona Workshop on Cardiomyocyte Biology: highlights from the Sixth International Workshop. PMID- 20588193 TI - Improvement of adherence to hand hygiene practice using a multimodal intervention program in a neonatal intensive care. AB - Nosocomial infections are serious complications among preterm infants admitted to neonatal intensive care units (NICU). Hand hygiene is one of the most effective measures to prevent these infections. This study, performed in a tertiary level NICU, highlights the importance of a multimodal intervention program for adherence to hand hygiene. The compliance with hand hygiene among health care workers of the NICU increased significantly from 23% in the baseline assessment to 50% in the second assessment and the incidence of sepsis decreased from 13.4% to 11.3% after implementation of an intervention program. PMID- 20588190 TI - Congestive heart failure: where homeostasis begets dyshomeostasis. AB - Despite today's standard of care, aimed at preventing homeostatic neurohormonal activation, one in every five patients recently hospitalized with congestive heart failure (CHF) will be readmitted within 30 days of discharge because of a recurrence of their symptoms and signs. In light of recent pathophysiological insights, it is now propitious to revisit CHF with a view toward complementary and evolving management strategies. CHF is a progressive systemic illness. Its features include: oxidative stress in diverse tissues; an immunostimulatory state with circulating proinflammatory cytokines; a wasting of soft tissues; and a resorption of bone. Its origins are rooted in homeostatic mechanisms gone awry to beget dyshomeostasis. For example, marked excretory losses of Ca2+ and Mg2+ accompany renin-angiotensin-aldosterone system activation, causing ionized hypocalcemia and hypomagnesemia that lead to secondary hyperparathyroidism with consequent bone resorption and a propensity to atraumatic fractures. Parathyroid hormone accounts for paradoxical intracellular Ca2+ overloading in diverse tissues and consequent systemic induction of oxidative stress. In cardiac myocytes and mitochondria, these events orchestrate opening of the mitochondrial permeability transition pore with an ensuing osmotic-based destruction of these organelles and resultant cardiomyocyte necrosis with myocardial scarring. Contemporaneous with Ca2+ and Mg2+ dyshomeostasis is hypozincemia and hyposelenemia, which compromise metalloenzyme-based antioxidant defenses, whereas hypovitaminosis D threatens Ca2+ stores needed to prevent secondary hyperparathyroidism. An intrinsically coupled dyshomeostasis of intracellular Ca2+ and Zn2+, representing pro-oxidant and antioxidant, respectively, is integral to regulating the mitochondrial redox state; it can be uncoupled by a Zn2+ supplement in favor of antioxidant defenses. Hence, the complementary use of nutriceuticals to nullify dyshomeostatic responses involving macro- and micronutrients should be considered. Evolving strategies with mitochondria targeted interventions interfering with their uptake of Ca2+ or serving as selective antioxidant or mitochondrial permeability transition pore inhibitor may also prove efficacious in the overall management of CHF. PMID- 20588194 TI - Childhood cancer in Iran. AB - This study tries to define the incidence, survival, and risk factors of childhood cancer in Iran. A literature review on published articles was conducted by using different search engine from November 1974 to October 2008. The incidence rate of childhood cancer in Iran was 48 to 112 and 51 to 144 per million among girls and boys in multi geographical settings, respectively. The most common cancer in children from 0 to 14 years old were leukemia (incidence rate=8 to 62/million), lymphoma (3 to 23), and central nervous system tumors (3 to 22). The mortality rate of childhood cancers was 42 and 49 per million among girls and boys, respectively in 2004. A positive association between ABO blood groups, family history of cancer, drug usage during pregnancy, fathers' job, history of radiation, and parental smoking habit were found with childhood leukemia. It is essential that the effect of geographical differences on childhood cancer incidence rates and high mortality rate to be investigated in future studies. PMID- 20588195 TI - Isolated gut relapse presenting as chronic diarrhea during maintenance therapy for acute lymphoblastic leukemia. AB - SUMMARY: Ten-year-old boy with acute lymphoblastic leukemia (ALL)-T cell subtype was on MRC UKALL 2003-based chemotherapy. Bone marrow attained remission after induction. After 8 months into maintenance, he presented with chronic diarrhea and weight loss. Search for infective and malabsorptive etiology was unrewarding. Infiltration with leukemic cells was seen in the lamina propria on mucosal biopsies of duodenum and colon. Marrow was in remission. Isolated gut relapse is exceedingly rare. It should be considered in the etiology of chronic diarrhea in patients with ALL, after common causes are excluded. PMID- 20588196 TI - Use of conventional fractionation with cyberknife in children: a report of 5 cases. AB - SUMMARY: The use of stereotactic radiotherapy with CyberKnife (Accuray Incorporated, Sunnyvale, CA) in adults is becoming more and more established. For children, there is no such consensus and the appropriate approach to this type of treatment is still debated. In the meantime, there seems to be a number of certain pediatric cases in which the use of CyberKnife within very strict limits is potentially justified. Here, we report the feasibility of and acute tolerance to radiotherapy with CyberKnife using conventional fractionation in 5 children. PMID- 20588197 TI - Cancer pain, suffering, and spirituality: a Middle Eastern Cancer Consortium meeting. PMID- 20588198 TI - Kaposiform hemangioendothelioma of the kidney: an unusual presentation of a rare vascular neoplasm. AB - Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive, vascular spindle-cell proliferation, with resemblance to Kaposi sarcoma. Usually, this tumor occurs in the skin and the retroperitoneum. We described a girl with a kidney localization and extension into the inferior vena cava and even into the right atrium. The case presented here is unique in 2 ways. First, kidney involvement of KHE has never been described in the literature until now. Second, and most remarkably, extensive tumor thrombosis suggests surgical excision even with cardiopulmonary bypass. The KHE of the kidney is a rare tumor but should be taken into account in the differential diagnosis with other pediatric renal neoplasms. PMID- 20588199 TI - Femoral neuropraxia after vaccination in a 3-month-old infant: a case report. AB - We report an incidence of a 3-month-old infant who developed femoral neuropraxia after vaccination (diphtheria, tetanus and acellular pertussis/inactivated poliovirus/haemophilus influenzae type B vaccine) in the thigh. To the best of our knowledge, femoral nerve injury after vaccination has not been reported in the literature before. However, this baby made good neurological recovery within 8 weeks after vaccination. PMID- 20588200 TI - Prognostic factors for pulmonary metastasectomy in the treatment of hepatocellular carcinoma. AB - BACKGROUND: This study aimed to present our experience with pulmonary metastasectomy in the treatment of hepatocellular carcinoma and to evaluate the prognostic factors. METHODS: The clinicopathologic data of 17 patients including presence of viral hepatitis, the serum alpha-fetoprotein (AFP) level, the number of metastases, and laterality were analyzed. The overall survival rates and the prognostic factors were estimated using the Kaplan-Meier method and Cox proportional hazards model for multivariate analysis. RESULTS: The median follow up periods after pulmonary resection and initial hepatic resection were 28.9 and 46.2 months, respectively. The actuarial overall 1-, 3-, and 5-year survival rates after pulmonary metastasectomy were 64.7 +/- 11.6%, 29.4 +/- 11.1%, and 11.8 +/- 7.8%, respectively. Using multivariate analysis, disease-free interval (DFI) of more than 24 months (hazard ratio = 2.36, 95% confidence interval = 1.33 25.33, p = 0.020) and AFP levels after pulmonary resection (hazard ratio = 51.3 95% confidence interval = 3.68-716.66, p = 0.003) were found to be independent prognostic factors. CONCLUSIONS: Although only a small number of patients were enrolled in this study, a disease-free interval more than 24 months and the serum AFP level after pulmonary metastasectomy might be important prognostic factors. PMID- 20588201 TI - The clinical value of lymphatic micrometastases in patients with non-small cell lung cancer. AB - INTRODUCTION: In early stage non-small cell lung cancer (NSCLC), presence of lymphatic micrometastases and isolated tumor cells, primarily detected by immunohistochemistry, is suggested to be a prognostic factor. However, there is no consensus whether immunohistochemistry should be used routinely in lymph node assessment.The goal of our study was to determine whether recurrent disease is associated with the presence of lymphatic micrometastases and/or isolated tumor cells, at the time of the lung resection. METHODS: We retrospectively analyzed the prevalence of lymphatic micrometastases and/or isolated tumor cells in two groups of patients, who underwent a curative resection for early stage NSCLC. Group I had a follow-up of 5 years without recurrent disease. Group II consisted of a matched group of patients with recurrent disease. Patients were originally classified as having negative mediastinal lymph nodes.All lymph nodes obtained by mediastinoscopy and thoracotomy were re-examined by serial sectioning and immunohistochemistry. RESULTS: Micrometastases and/or isolated tumor cells were found in one of 16 patients in group I, which was significantly different from six of 16 patients in group II. (Fisher exact test, 4.6; p, 0.04; risk ratio, 2.4).Serial sectioning and immunohistochemistry did not change N-stage for the single patient in group I, in contrast to all six patients in group II. CONCLUSION: Presence of lymphatic micrometastases and/or isolated tumor cells is associated with distant recurrence in patients with early stage NSCLC. We recommend the routine use of serial sectioning and immunohistochemistry in lymph node assessment to improve the accuracy of staging. PMID- 20588202 TI - Synchrony of audio-visual speech stimuli modulates left superior temporal sulcus. AB - The superior temporal sulcus has been suggested to play a significant role in the integration of auditory and visual sensory information. Here, we presented vowels and short video clips of the corresponding articulatory gestures to healthy adult humans with two auditory-visual stimulus intervals during sparse sampling 3-T functional magnetic resonance imaging to detect which brain areas are sensitive to synchrony of speech sounds and associated articulatory gestures. The upper bank of the left middle superior temporal sulcus showed stronger activation during naturally asynchronous stimulation than during simultaneous stimulus presentation. It is possible that this reflects sensitivity of the left middle superior temporal sulcus to temporal synchrony of audio-visual speech stimuli. PMID- 20588203 TI - Effects of the CYP3A5*3 variant on cyclosporine exposure and acute rejection rate in renal transplant patients: a meta-analysis. AB - BACKGROUND: Whether the loss-of-function allele CYP3A5*3 variant is associated with significantly impaired metabolism of cyclosporine A (CsA) in transplant patients is still controversial because of the lack of prospective, large-scale clinical studies performed among diversely ethnic populations. OBJECTIVES: This meta-analysis was designed to determine whether the CYP3A5*3 variant could affect CsA blood concentrations and the rate of acute rejection in renal transplant recipients. METHODS AND RESULTS: All relevant publications were retrieved online from 1966 to March 2010, in which 14 studies were chosen, and 1821 renal transplant patients were enrolled. The results showed that there were significant differences in the CsA dose-adjusted trough concentration (C0) between the CYP3A5*3/*3 and CYP3A5*1/*1 carriers [weighted mean difference (WMD): 10.06 mug/l per mg/kg, 95% confidence interval (CI): 3.12-17.00, P=0.004] and between the non CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: 8.32 mug/l per mg/kg, 95% CI: 3.16-13.49, P=0.002). In addition, a subgroup analysis stratified by ethnicity indicated that a significant difference in CsA dose-adjusted C0 was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers in Asian patients, but not in Caucasian patients. Moreover, a significant difference in the mean daily dose was observed between the non CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: -0.19 mg/kg, 95% CI: -0.31 to -0.07, P=0.002). However, the meta-analysis suggested that there was little or no association of the CYP3A5*3 variant with the acute rejection rate in renal transplant patients treated with CsA [odds ratio=0.94, 95% CI: 0.57-1.54, P=0.80]. CONCLUSION: We concluded that the CYP3A5*3 variant could be associated, to a certain extent, with increased CsA dose-adjusted C0 in blood and reduced mean daily doses, but that this genetic variant allele seemed to have little effect on the acute rejection rate in renal transplant patients taking CsA. PMID- 20588204 TI - Natural evolution of fundus autofluorescence findings in multiple evanescent white dot syndrome: a long-term follow-up. AB - PURPOSE: The purpose of the study was to investigate the natural evolution of fundus autofluorescence (FAF) findings in eyes with multiple evanescent white dot syndrome. METHODS: This was a retrospective, observational case series of nine eyes of eight consecutive patients with multiple evanescent white dot syndrome who underwent color fundus photographs, fluorescein and indocyanine green angiography, and FAF photography in two referral practices. RESULTS: The mean follow-up was 8.6 months (range, 3-14 months). In the acute/ subacute phase, FAF showed 1) hypoautofluorescent areas, <=50 MUm in size, mostly concentrated around the optic disk and posterior pole; and 2) areas of increased autofluorescence usually found in correspondence to the white dots seen ophthalmoscopically. During the follow-up period, some of the hypoautofluorescent areas faded away, others persisted; the areas originally showing increased autofluorescence variably tended to: 1) become smaller and more demarcated; 2) retract centripetally becoming small hyper-autofluorescent areas surrounded by an hypoautofluorescent halo; 3) turn into areas of decreased autofluorescence; or 4) disappear without becoming hypofluorescent. CONCLUSION: Multiple evanescent white dot syndrome represents a unique model to study the natural evolution of FAF findings in chorioretinal affections, from the acute phase to resolution; FAF findings, evaluated along with fluorescein and indocyanine green angiography features, can expand our understanding about retinal pigment epithelium and retinal involvement in this rare chorioretinal disorder. PMID- 20588205 TI - Comparison of 20-gauge transconjunctival sutureless vitrectomy with conventional vitrectomy. AB - PURPOSE: The purpose of the study was to compare the efficacy and safety of a transconjunctival sutureless technique for pars plana vitrectomy using conventional 20-gauge instruments versus the conventional technique. METHODS: Clinical data were reviewed retrospectively for a consecutive series of patients who underwent transconjunctival sutureless vitrectomy (TSV; 38 eyes of 37 patients) and a control group who underwent vitrectomy using the conventional technique (38 eyes of 38 patients). RESULTS: Eighty-nine of 107 sclerotomies (83.2%) in the TSV group self-sealed without the need for sutures. The TSV group showed earlier visual improvement from baseline, as early as 7 postoperative days, compared with 60 days in the conventional group. This was attributed to less surgically induced astigmatism in the TSV group; mean astigmatism at baseline and postoperative days 7, 30, and 90 was -1.05 diopter (D), -2.53 D, 1.32 D, and -1.09 D, respectively, in the TSV group and -1.09 D, -3.91 D (P = 0.0285), -2.57 D (P = 0.0203), and -1.18 D, respectively, in the conventional group. No serious complications were observed in either group, including postoperative hypotony, wound leakage, or endophthalmitis. CONCLUSION: The 20 gauge TSV technique is as effective as the conventional technique and offers earlier postoperative recovery. PMID- 20588206 TI - Intragraft tubular vimentin and CD44 expression correlate with long-term renal allograft function and interstitial fibrosis and tubular atrophy. AB - BACKGROUND: Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker), both involved in renal fibrosis, can operate as surrogate markers for late IF/TA and renal function. Furthermore, we wanted to establish the interrater reproducibility for the scoring system, which can be a problem in histologic assessments. METHODS: Six-month protocol renal allograft biopsies (n=30 for matching 12 months estimated glomerular filtration rate (eGFR) from which 20 matched the 12-month protocol biopsy) were immunostained for CD44 and vimentin, semiquantitatively scored by three observers of two centers, and correlated with IF/TA and eGFR at 12 months. RESULTS: The interobserver agreement was excellent for CD44 (Kendall's W-coefficient: 0.69; P<0.001) and vimentin (Kendall's W coefficient: 0.79; P<0.001). CD44 and vimentin expression at 6 months were significantly correlated with IF/TA (rho=0.481 for CD44 and rho=0.619 for vimentin) and eGFR (rho=-0.569 for CD44 and rho=-0.376 for vimentin) at 12 months. CONCLUSIONS: Summarizing, de novo tubular expression of CD44 and vimentin can function as surrogate marker for IF/TA and eGFR at 12 months. Further area under receiver operator characteristic curve analysis has to establish the predictive value for both biomarkers. PMID- 20588207 TI - Living donor liver transplantation in patients older than 60 years. AB - BACKGROUND: Living donor liver transplantation (LDLT) has been performed in adult patients. However, there are a few reports on how recipient age affects the outcome of LDLT. This study assessed LDLT outcome in patients aged 60 years or older. METHODS: A total of 267 patients were enrolled and classified into two groups: those younger than 60 years (younger group, n=210) and those aged 60 years or older (older group, n=57). The 6-month and 1-, 3-, and 5-year patient survivals and the incidence of complications were compared. Multivariate analysis was performed to identify the risk factors. RESULTS: Fifty-five of 57 (96.5%) donors in the older group were younger than 50 years (range 25-47 years), whereas only 177 of 210 (84.3%) donors in the younger group were younger than 50 years (P<0.0001). The 6-month and 1-, 3-, and 5-year patient survival rates of the older group were 92.9%, 85.3%, 72.7%, and 70.3%, respectively, whereas those of the younger group were 87.4%, 85.8%, 80.2%, and 78.2%, respectively. Neither difference was significant. A multivariate analysis revealed that the presence of diabetes, lack of hepatocellular carcinoma, and Model for End-Stage Liver Disease (MELD) Score more than or equal to 20 were independent risk factors for survival less than 1 year after LDLT (P=0.0003, P=0.014, and P=0.041, respectively). Another multivariate analysis revealed that the lack of consanguinity, MELD Score more than or equal to 20, and male recipient were independent risk factors for death 1 year or more after LDLT (P=0.004, P=0.005, and P=0.015, respectively). CONCLUSION: Recipient age did not affect LDLT outcome when patients with MELD Score less than 20 received grafts from consanguineous donors. PMID- 20588208 TI - Nuclear Cardiology at the eve of the new decade: the continuous changes needed to remain stable. PMID- 20588209 TI - The clinician's view of cardiac diagnostic imaging. AB - In the last 30 years, non-invasive cardiac imaging was employed for the diagnostic and prognostic assessment of patients with suspected or known coronary artery disease. Nuclear myocardial perfusion scintigraphy or stress echocardiography provide a high sensitivity and specificity in the detection of functionally significant coronary artery disease (CAD) and demonstrated incremental diagnostic and prognostic value over exercise electrocardiography and clinical variables. Recently, cardiac computed tomography has been increasingly used a non-invasive tool for the detection and quantification of coronary artery stenoses and calcifications. The increase in this technical "offer" induces a significant increase in the "demand" for non-invasive imaging assessment, with a rise in the number of imaging studies performed in the last years, which appropriateness, however, is often questionable. A critical evaluation of the use of imaging techniques in different clinical scenarios is briefly discussed. PMID- 20588210 TI - Gated SPECT myocardial perfusion imaging: the further improvements of an excellent tool. AB - Cardiac imaging with gated single-photon emission computed tomography (SPECT) allows the evaluation of myocardial perfusion and analysis of global and regional left ventricular function. Gated SPECT is a validated and established diagnostic and prognostic method for evaluation of patients with suspected and known coronary artery disease. Significant improvements in software and gamma camera technology in SPECT cardiac imaging have been obtained. New detectors open a scenario for faster imaging with lower radiation dose to the patient. Appropriate use of the SPECT imaging is regulated by evidence-based guidelines and appropriateness criteria as well as by third-party payers in an effort to restrain the unsustainable growth of imaging testing recently observed. Future of cardiac SPECT imaging will be driven by societal demand for cost effective, accurate, and safe testing, which will improve meaningfully patients' management and outcomes. PMID- 20588211 TI - Myocardial perfusion PET/CT to evaluate known and suspected coronary artery disease. AB - There is an extensive literature validating the use of positron emission tomography (PET) for the evaluation of regional myocardial perfusion. With PET perfusion imaging, the reported average sensitivity for detecting angiographic stenosis of >50% is 91% (range 83-100%) and the specificity is 89% (range 73 100%). While a sensitive approach for diagnosing obstructive coronary artery disease (CAD), PET (like single photon emission computed tomography) also underestimates the extent of underlying disease. However, PET's unique ability to record changes (from baseline) in left ventricular function during peak stress, as well as quantify myocardial perfusion (in mL/min/g of tissue) and derive estimates of myocardial perfusion reserve can help mitigate this limitation. Recent data suggest that PET can also provide accurate risk prediction in patients with known or suspected CAD, and that this information is additive to clinical risk prediction models. The integration of computed tomography (CT) in hybrid PET/CT scanners offers not only accurate and efficient attenuation correction, but also the possibility of providing diagnostic and prognostic information with the addition of coronary artery calcium scoring and CT coronary angiography. The combination of short lived PET radiopharmaceuticals (e.g., Rubidium-82 and N-13 ammonia) with new technology for the acquisition of the CT imaging data (e.g., prospective gating) allow a comprehensive examination of anatomy and function at a relatively low radiation dose. PMID- 20588212 TI - Role of quantitative myocardial perfusion PET as a clinical translation research tool. AB - In biology and medicine, "translational research" indicates the "translation" from the language of molecular biology in animal experiments to human physiology in order to improve our insight into the molecular mechanisms underlying the progression of cardiac diseases and to verify the mechanism of action or the potential of newly developed drugs. Positron emission tomography (PET) plays a major role in this setting due to four major characteristics: 1) extremely high sensitivity; 2) excellent temporal resolution; 3) the possibility to label molecules without altering their chemical properties and 4) the short half live of isotopes. These features make PET as an unique method able to display in the same image format different variables related to the physiology of the myocardium under different pathophysiological states, thus allowing a more precise geographical correlation of the different processes underlying disease or drug effect. This paper will review the literature available about the utilization of PET in the setting of cardiovascular pathophysiology and drug development. This task will be accomplished by describing the theory and practice of methods available to measure myocardial blood flow and to characterize myocardial metabolism in order to obtain a more precise clarification of disease phenotype. Similarly the potential of this method in defining drug effectiveness in clinical trial will be discussed, in order to offer an overview of the potential for the noninvasive measurement of physiological variables in the modern medicine. PMID- 20588213 TI - Metabolic imaging in myocardial ischemia and heart failure. AB - Myocardial ischemia and heart failure are accompanied by well characterized changes in myocardial substrate metabolism. While the normal heart in the fasting state mostly relies on oxidation of fatty acids for energy production, acute myocardial ischaemia is accompanied by increased exogenous myocardial glucose uptake and suppressed utilization of fatty acids. This metabolic shift can be detected using metabolic imaging using labeled glucose and fatty acid analogs. Recently, also specific tracers for the detection of myocardial hypoxia have been tested. In the assessment of myocardial viability metabolic imaging has an established role. Metabolic imaging has also greatly improved our understanding about metabolic derangements in the failing heart and currently metabolic modulation as a therapy of heart failure is studied. While experimental and clinical results are promising, larger clinical trials are warranted to better understand the value of metabolic imaging in the detection and prognosis of ischemic heart disease. PMID- 20588214 TI - Emerging role of nuclear cardiology in heart failure. AB - The management of patients with heart failure requires the integration of clinical skills and accurate complementary tests for the correct diagnosis, treatment and estimation of individual prognosis. Identification of those patients most at risk of death, and those most likely to benefit from currently available treatment technologies, remains a challenge. Although the basic characterization of patients with heart failure is supported primarily by the assessment of the left ventricular function, there are several nuclear cardiology techniques and tracers, either available or under development, which can provide important noninvasive imaging insights into the pathophysiology, prognosis and management of patients with heart failure. Nuclear techniques for molecular imaging of the myocardium such as those involved in the processes of myocardial perfusion, metabolism and viability, cellular injury, dyssynchrony, intersticial dysregulation and neurohormonal receptor function may facilitate better clinical outcomes for patients with heart failure. This review mainly focuses on cardiac sympathetic imaging, as other modalities of nuclear cardiology in the assessment of patients with HF are reviewed more extensively in other sections of this issue. PMID- 20588215 TI - Application of technetium-99m sestamibi single photon emission computed tomography in acute myocardial infarction: measuring the efficacy of therapy. AB - Infarct size and myocardial salvage measured by technetium (Tc)-99m sestamibi single photon emission computed tomography (SPECT) imaging have been applied as surrogate endpoints in clinical trials of acute myocardial infarction (MI). The major advantage of these endpoints over mortality is the ability to use much smaller sample sizes to compare different treatment strategies in acute MI. Multiple categories of evidence validate SPECT infarct size and myocardial salvage as surrogate endpoints, including: association with other variables used to measure infarct size; association with markers of myocardial perfusion; identification of myocardial fibrosis in pathology specimens; prediction of improvement in dysfunctional myocardial segments following revascularization; correlation between infarct size and mortality; and, demonstration that therapies which result in smaller infarct size also result in better clinical outcome in the same patients. These SPECT endpoints have been applied in over 30 clinical acute MI trials. Approximately one-third of these trials reported positive results in the intervention group or a subset of the intervention group. SPECT infarct size and myocardial salvage are the most extensively validated and widely applied surrogate endpoints in the setting of acute MI. PMID- 20588216 TI - Molecular imaging in nuclear cardiology: translating research concepts into clinical applications. AB - Molecular imaging provides a novel approach for the early non-invasive detection of critical molecular or cellular processes associated with initiation of disease, before the manifestation of anatomical changes or late physiological consequences. This article reviews the current and future role of molecular imaging in evaluation of cardiovascular diseases, including the early detection of atherosclerosis, ischemia-induced angiogenesis, and post-infarction left ventricular remodeling. Cardiovascular molecular imaging with radiolabeled probes has already translated into clinical practice in the evaluation of critical metabolic and receptor mediated process in the heart, however, the true clinical impact of targeted molecular imaging has not yet been realized. The advancement of cardiovascular molecular imaging will require the development of novel targeted probes, hybrid high-sensitivity and high-resolution imaging systems, and the collaboration of basic and clinical imaging communities. The application of molecular imaging in combination with conventional anatomical and physiological imaging should provide new insights into the pathophysiology of disease that may allow a more personalized approach to the evaluation and management of cardiovascular diseases. PMID- 20588217 TI - Biomechanical evaluation of dental implants in D1 and D4 bone by Finite Element Analysis. AB - AIM: The aim of the present study was to analyze stress and strain distribution in dental implants with different abutment's inclination inserted in D1 and D4 bone. METHODS: The biomechanical behavior of 5 mm x 16 mm dental implants with straight, 15 degrees and 25 degrees angulated abutments subjected to static loads, in contact with D1 and D4 bone, was evaluated by Finite Element Analysis (FEA). RESULTS: The lowest stress and strain values were found in the system composed by implants with straight abutments loaded with a 200-N vertical strength, while the highest stress and strain values were found in implants with 15 degrees angulated abutment loaded with a tilted strength (FY=200 N and FZ=140 N). Stress value increased from D1 to D4 bone, while strain value decreased due to the effect of normal elasticity mode of biological tissues. CONCLUSION: The different stress and strain distribution in D1 and D4 bone tissue surrounding dental implants with a tapered neck could favor prosthetic load and play a role in implant long-term success. PMID- 20588218 TI - Ostheosynthesis plates, screws, xenogenic graft and resorbable barriers for preimplant and peri-implant surgery. AB - AIM: The guided bone regeneration (GBR) procedure allows the regeneration of bone in implant surgery. A variety of GBR procedures to provide the bony-support for implant placement have been described and a variety of devices to perform this procedures have been used. The authors have carried out a retrospective study on the use of ostheosynthesis plates, screws, xenogenic bone grafting material and resorbable barriers for implant and preimplant surgery. METHODS: Fourteen partially edentulous patients were treated by a single surgeon in a private dental clinic in Italy. Patients age ranged between 28 and 52 years old. Every patients was treated with GBR technique performed with the use of ostheosynthesis plate and screws, xenogenic bone grafting material and resorbable barriers in staged or simultaneous implant placement. RESULTS: Twenty-one implants were placed and no-one failed, all planned prostheses were delivered. In all the cases a complete bone regeneration was obtained. CONCLUSION: The outcomes of the study allow to state that the GBR technique performed with ostheosynthesis plates, screws, xenogenic graft and resorbable barriers is a safe alternative to the others well established GBR procedure. PMID- 20588219 TI - Mucoepidermoid carcinoma: a retrospective study. AB - AIM: The aim of this study was to review the cases of mucoepidermoid carcinoma diagnosed at the Stomatology Service of Sao Lucas Hospital (PUCRS). METHODS: Medical charts were reviewed focusing on the sex and age of the patients, clinical aspect, anatomic site, signs and symptoms, size and histological grade of the lesion. RESULTS AND CONCLUSION: Of the 19383 patients who were seen between 1978 and 2009, 675 (3.48%) had a histopathological diagnosis of malignant neoplasm of the oral maxillofacial region including 12 (1.78%) cases of mucoepidermoid carcinoma. The mean age of patients with mucoepidermoid carcinoma was 43.8 years, and there was a predilection for males (58.7%). All cases occurred in the minor salivary glands, and the palate was the site most frequently affected (41.7%). Pain and local irritation were present in 50% of cases, and the size of lesions ranged from 0.3 cm to 5.0 cm. The histological classification of low- and intermediate-grade occurred at the same frequency (36.4%), and symptoms (pain, local irritation) occurred indiscriminately in different grades of tumor. PMID- 20588220 TI - Scanning electron microscopy analysis of two methods of root-end preparation. AB - AIM: This study evaluated changes in dental tissues of the apical third after root-end preparation. METHODS: Sixty permanent single-rooted human teeth were used after apicectomy at 90 degrees to the long axis of the tooth. Crown removal was performed with a double-faced diamond disk, on a straight handpiece, and specimen standard length was set at 8 mm. Root-end cavities were prepared with an ultrasound system in 30 teeth (G1); in the other teeth, the cavities were prepared with a bur using a contra-angle and micro-handpiece (G2). The width of the root-end cavity was the diameter of the tip or bur, and its depth was 3 mm. Each group was divided into two subgroups with 15 teeth each; 37% phosphoric acid was applied to specimens in subgroups G1B and G2B. All specimens were photographed under scanning electron microscopy. Images were evaluated descriptively and data were compared for fractures, smear layer, uniform inner surface, regular edges, and whether root-end preparation including the whole foramen. A chi-square test and the kappa index were used to analyze results statistically. RESULTS: Only two variables, uniform inner surface and regular edge, varied according to the method used (bur or ultrasound). The presence of smear layer was associated with the use of phosphoric acid. CONCLUSION: Both methods seemed to be adequate for use in endodontic surgeries. PMID- 20588221 TI - Effect of monomer content in the monomer-polymer proportion on the adaptation of complete denture bases. AB - AIM: This study verified the effect of the monomer/polymer proportion on the base adaptation of the complete upper dentures. METHODS: Thirty stone cast-wax baseplate sets were packed in metallic flasks and the acrylic resin polymerized in water at 74 degrees C for nine hours. Three transverse cuts were made through each stone cast-resin base set, corresponding to regions: A) canines (anterior); B) first molars (median), and C) posterior palate (posterior). Measurements were made using an optical micrometer at five points for each cut to determine base adaptation: left and right marginal limits of the flanges, left and right ridge crests, and midline. Data were analyzed using to ANOVA and Tukey's test (5%). RESULTS: In region A there was significant difference among the monomer-polymer proportions, with a greater value of misfit for the content -25% monomer group and lower for the manufacturer's proportion group. In region B there was significant difference between the manufacturer's content (lowest value) and the monomer contents of +25% and -25% (both statistically similar). In region C there was significant difference among the monomer-polymer proportions, with greater value for the -25% monomer group than for the manufacturer's proportion. There was significant difference when the regions were compared in relation to the same monomer content. The best adaptation was in the region A and the worst in the region C. CONCLUSION: The amount of monomer exerted different effects on the adaptation of the denture base. In all regions, the smallest misfit was observed when the manufacturer's recommended proportion was used and the greatest misfit was observed in the -25% monomer. PMID- 20588222 TI - Intraosseous anastomosis in the maxillary sinus. AB - AIM: During sinus-lift surgery, certain intra-osseous vessels may be accidentally cut and this cause bleeding complications in approximately 20% of osteotomies. Therefore, understanding vascular details of the maxilla is very important for the surgeon. Here, we have given an anatomical overview of maxillary sinus vascularization through anatomical dissection. We have analyzed the distribution, localization and distance from the alveolar ridge of intraosseous branches of the maxillary artery found during sinus lift surgery. METHODS: Fifty-six maxillary bone doors were made bilaterally in twenty-eight unfixed cadavers; the doors were made between the first molar and the second molar (24 doors) or between the first and the second premolar (32 doors). RESULTS: Intraosseous arteries were found in 37 maxillary bones (66%). The average height of the artery from the alveolar crest was 13+/-3.2 mm in the distal doors and 18 +/- 6.1 mm in the mesial doors. Generally, the intraosseous maxillary branches ran caudo-rostrally; but in five maxillae, we found two parallel arteries, while in three cases the maxillary artery ran vertically. No differences were found between the left and right side. CONCLUSION: The risk of vascular damage in sinus floor elevation surgery is a real problem for the oral surgeon. Detailed anatomical knowledge about sinus vascularization is very important to reduce the risk of vascular damage and bleeding. In addition the visualization of sinus anastomosis by radiology and less invasive surgery, such as piezo-surgery, could be helpful. PMID- 20588223 TI - Temporal localization of osteocalcin protein during healing of tooth extraction sockets in rats. AB - AIM: The aim of this study was to evaluate the expression of osteocalcin protein during the alveolar bone healing process in rats. METHODS: Twenty four rats were used in this study and, after anesthetic induction, they had their right upper incisors extracted. At 7, 14, 21 and 28 days after the tooth extraction, the animals were injected 4% formaldehyde. The histological tissue pieces were colored in hematoxilin and eosin and the immunohistochemistry reaction for osteocalcin was performed. RESULTS: At seven days lesser neoformed trabeculae bone and a small quantity of osteocalcin labeling were observed. At 14 and 21 days a larger quantity of neoformed trabeculae bone and higher osteocalcin values were detected. At 28 days the largest quantity of neoformed trabeculae bone and a decrease on the amount of osteocalcin immunolabelling were noticed. CONCLUSION: According to our results and considering the limits of the present study it is possible to conclude that a greater osteocalcin expression is observed at 14 and 21 days postoperatively, characterizing the periods when intense mineralization of the bone tissue occurs during the alveolar bone healing process. PMID- 20588224 TI - Cone beam computed tomography role in diagnosis and treatment of impacted canine patient's: a case report. AB - A tooth is impacted when its apex is formed but does not erupt as expected during the physiological timeframe of eruption. The frequency with which the upper canine is impacted in the sample examined varies from 1% to 5% of the population in the second decade of life. The most frequent causes of inclusion of the upper canine are: lack of resorption or precocious loss of the root of the deciduous, agenesis of the lateral, an anomaly in its shape, lack of space in the arch, presence of a mechanical obstacle to the eruption, and lastly due to hereditary factors. When dental impaction is suspected, radiographic examination is indicated to evaluate the effect that the impacted element is having in the context of the osseous structure and to evaluate its relationships with adjacent teeth, the presence of mechanical obstacles, the placement of the inclusion and its orientation in space, how well developed the root is, and any anomalies in its shape. In addition to the classic orthopantomography (OPT), endoral radiography, teleradiography, can be used in order to obtain three-dimensional and life-size images, techniques of computed tomography (CT). In particular, cone beam CT, obtains this type of image using a radioactive dose comparable to that obtained summarizing the classic radiographic examinations requested by an orthodontist and moreover less that that administered when using classic multi layer spiral CT medical equipment. This case report describes the diagnostic iter and orthodontic-surgical treatment of a patient with enclosure of the right upper canine. PMID- 20588225 TI - Acantholytic squamous cell carcinoma of the oral cavity: an uncommon histological variant of squamous cell carcinoma. AB - Acantholytic squamous cell carcinoma is a rare and aggressive histological variant of squamous cell carcinoma, characterized by tubular and alveolar patterns as a consequence of the acantholysis. We report a case of acantholytic squamous cell carcinoma in a 70-year-old woman, who was admitted to our institution for the progressively enlarging exophytic and ulcerated lesion. We report this interesting lesion due to the rarity of acantholytic variant of squamous cell carcinoma and the literature is briefly reviewed. PMID- 20588226 TI - Proceedings of the 16th National Congress of the Italian Society of Neonatology, 19-22 May 2010, Bari, Italy. PMID- 20588227 TI - Women with incorrect pelvic floor statics: a biomechanical answer to the mechanical loading of the vagina-endopelvic fascia complex. AB - OBJECTIVE: This work focuses on finding method for detecting the elementary mechanical characteristics of the vagina-endopelvic fascia complex, aimed at providing results for use in optimizing solutions for stability defects of the pelvic floor. MATERIALS AND METHODS: Two experiments have already been carried out that have enabled monitoring of the reaction of tissue complex samples to a selected load. The elastic properties of samples under a simple pull load were evaluated. The monitored property in the first experiment was the maximum reference tension at the moment of rupture of the sample in relation to the non deformed section. We evaluated data from measurements on 11 samples within the scope of the first experiment. For data processing from the second experiment we used a linear-elastic model of the sample, formed by parallel connection of basic mechanical elements - springs - that represented the endopelvic fascia and the vaginal wall. The relevant rigidities were used for a description of their properties. Five samples were used for this experiment. RESULTS: An important discovery was that the endopelvic fascia tears apart after a longer period of time than the vaginal wall during the pull test. The results show considerable variability among individuals, but the pattern of curves is similar in all test cases. In all measured data we found a rigidity increase zone, a maximum rigidity zone and a gradual rigidity decrease zone before terminal damage in the response. CONCLUSIONS: The results presented here show quite broad interindividual variability of the mechanical properties of the vaginal wall-endopelvic fascia complex. It appears that the mechanical properties of the tissue complex change with number of pregnancies, and are affected by diseases, by physical load or by the presence of other factors, e.g. obesity. PMID- 20588228 TI - The role of environmental factors in autoimmune thyroiditis. AB - Environmental factors can play an important role in the development of autoimmune thyroiditis (AT) and other autoimmune diseases. This article reviews the role of heavy metals and infectious agents in AT. Currently, the genes responsible for a metal-induced pathology are known in experimental animals but similar knowledge is lacking in man. Metals such as nickel or mercury induce delayed type T cell hypersensitivity (allergy) which is relatively common, especially in women. T cell allergy can be studied with the lymphocyte transformation test, LTT-MELISA. It has been found that patients with AT and other autoimmune diseases, such as multiple sclerosis, psoriasis, systemic lupus erythematosus and atopic eczema, show increased lymphocyte reactivity in vitro to inorganic mercury, nickel and other metals compared to healthy controls. The important source of mercury is dental amalgam. Replacement of amalgam in mercury-allergic subjects resulted in improvement of health in about 70% of patients. Several laboratory parameters such as mercury-specific lymphocyte responses in vitro and anti-thyroid autoantibodies were normalized as well. In contrast, no changes in health and laboratory results were observed in mercury-allergic patients who did not have their amalgams replaced. The same was true for non-allergic patients who underwent amalgam replacement. Infectious agents such as Helicobacter pylori (Hp) may cause chronic inflammation and autoimmune reactivity in susceptible subjects. The results of in vitro experiments performed with lymphocytes from Hp infected patients indicate that Hp can cause immunosuppression which might be eliminated by successful eradication therapy. In conclusion, heavy metals and Hp infection may play an important role in AT. Laboratory tests, such as LTT-MELISA, can help to determine the specific etiological agents causing inflammation in individual patients. The treatment of AT and other autoimmune diseases might be improved if such agents are eliminated and any future exposure restricted. PMID- 20588229 TI - Suppression of melatonin secretion in healthy subjects with eyeglass LED delivery system. AB - OBJECTIVE: Practicability remains a problem in light therapy of biological rhythm disorders. We report here the effect on melatonin secretion of a device consisting of a prototype of eyeglasses including light emitting diodes (LED) in lenses (Somnavue). METHODS: Light (1,200 lx) was administered in a randomised crossover design to ten healthy subjects with Somnavue for 1 or 2 hours, Lumino (a helmet which administers light) for 1 hour, and placebo, beginning at 01:00 h. Plasma melatonin concentrations were evaluated between 20:00-05:00 h. RESULTS: Multiple comparisons showed differences between placebo and Somnavue administered for one or two hours (p<0.01 and p<0.05 respectively) and Lumino and placebo (p<0.05). CONCLUSIONS: In conclusion, Somnavue was able to suppress melatonin. The development of such a device could increase adherence with light treatment in SAD or circadian rhythm sleep disorders. PMID- 20588230 TI - Spinal cord atrophy in triple A syndrome associated with a novel compound heterozygous mutation. AB - A 38-year-old male patient was admitted with slowly progressive spastic gait disturbance. Imaging revealed general spinal cord atrophy. Because of adrenal insufficiency, alacrima and achalasia, triple A syndrome was suspected. This is a case report of a triple A syndrome patient with a predominance of neurological features and a new heterozygous compound mutation in triple A syndrome gene. PMID- 20588231 TI - Reducing symptoms in women with chronic anorexia nervosa. A pilot study on the effects of bright light therapy. AB - OBJECTIVE: To examine the effect of bright light therapy on the sleep-wake rhythm, the menstrual cycle, mood, and key eating pathology symptoms in chronic anorexia nervosa. METHODS: Five chronic anorectic women (mean duration of illness: 15.3 years) received 5 daily sessions of 30 minutes bright light therapy (10,000 LUX). Participants completed a diagnostic interview and questionnaires at pre-test, post-test and at a three month follow-up. RESULTS: At follow up there was a slight improvement on core eating pathology, a fair decrease of depressive symptoms and an clinically important improvement on global distress. CONCLUSIONS: Bright light therapy has on short term a positive effect on the physiological and psychological well being of chronic anorectic women. However, at follow-up the effects were partly lost. It is recommended to enhance the exposure period and repeat the treatment after 3 months. PMID- 20588232 TI - Proinflammatory and immunosuppressive serum, ascites and cyst fluid cytokines in patients with early and advanced ovarian cancer and benign ovarian tumors. AB - OBJECTIVE: To analyze the profiles of interleukin-2 (IL-2), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF beta1) and interferon-gamma (IFN-gamma) in serum and the tumor microenvironment (cyst fluid, ascites) in women with ovarian cancer or benign ovarian tumors to find the differences in their immunological status. We also estimated serum cytokines as biomarkers to distinguish preoperatively between malignant or benign character of tumors. DESIGN: Prospective study. SETTING: Tertiary referral hospital. POPULATION: 51 women with epithelial ovarian cancer, 26 with benign ovarian tumors of epithelial origin and 21 healthy controls. METHODS: The levels of cytokines were measured using ELISA sets. RESULTS: We did not found differences in the levels of IFN-gamma, TNF-alpha and IL-2 in all fluids isolated from patients with malignant or benign tumors. Women with advanced cancer had significantly higher serum IL-6, IL-10 and TGF-beta1 levels than women with early stages or benign tumors. Moreover, women with very advanced cancer in whom the optimal cytoreduction was disabled had the highest serum levels of IL-10, TGF beta1 and IL-8. The concentrations of IL-6 and IL-8 were higher in ascites of cancer patients than in ascites of women with benign tumors. The areas under curves constructed for the selected cutoff serum cytokines levels (AUC-ROC) showed good predictive values for IL-6 (0.87), IL-10 (0.836) and IL-8 (0.797). CONCLUSIONS: Our results indicate on intensified inflammatory process in women with ovarian cancer (accompanied by their immunosuppression). Preoperative analysis of serum IL-6, IL-10 and IL-8 may improve the differential diagnosis of ovarian tumors. PMID- 20588233 TI - Presence of secretory cellular apoptosis susceptibility protein in cerebrospinal fluids of patients with intracerebral hemorrhage caused by stroke and neurotrauma. AB - OBJECTIVE: The blood-brain barrier (BBB) is a specialized structure that separates blood vessels from the central nervous system (CNS) and restricts the entry of biomolecules and cells into the brain. Matrix metalloproteinase-2 (MMP 2) produced by interferon-gamma-activated microglia (brain macrophages) is essential for disrupting the glia limitans of BBB, which is critical for lymphocytes penetration into brain capillaries in various CNS disorders. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to regulate MMP-2 secretion. METHODS: We examined if CSE1L played a role in regulating the progression of intracerebral brain hemorrhage disorders. RESULTS: CSE1L was detected by immunoblotting in cerebrospinal fluids (CSFs) of patients with intracerebral hemorrhage brain disorders, including stroke and neurotrauma. Interferon-gamma treatment induced CSE1L expression and increased the secretions of CSE1L and MMP-2 by U937 macrophages. Moreover, tranfection of U937 macrophages with siRNA that targeted CSE1L inhibited interferon-gamma-induced CSE1L and MMP-2 secretion by U937 macrophages. The numbers of lymphocytes in CSF were correlated with the levels of CSE1L and MMP-2 in patients' CSF. CONCLUSIONS: Our results suggest that CSE1L plays a role in regulating MMP-2-mediated BBB breakdown and it may be a target for control of BBB permeability in intracerebral brain hemorrhage disorders. PMID- 20588234 TI - Posterior Reversible Encephalopathy Syndrome (PRES) in 5-year-old girl with nephrotic syndrome. AB - OBJECTIVE: Posterior Reversible Encephalopathy Syndrome (PRES) is a rare complication of nephrotic syndrome in children. This clinical condition is caused by localized brain angioedema mostly in parieto-occipital region and results in dramatic and acute features as sudden loss of consciousness, epileptic paroxysms, strong headache or visual disturbances. Uncontrolled hypertension often participates in PRES development. CASE: We present the case of a 5-year-old girl treated for relapse of nephrotic syndrome. RESULTS: At the time of edema regression and weight reduction, a sudden loss of consciousness and worsening of hypertension occurred. Brain MRI demonstrated extended multifocal changes strongly suspicious of encephalitis. After exclusion of herpetic encephalitis, the clinical picture was classified as PRES. Successful antihypertensive treatment led to general improvement of the girl's health within 48 hours and resolution of MRI brain hyperintensities occurred within the next three months. CONCLUSIONS: The aim of our case report is to us remind of possible development of PRES at the time of edema regression in nephrotic syndrome. PMID- 20588235 TI - Neuroendocrine evidence of normal hypothalamus-pituitary dopaminergic function in Huntington's disease. AB - OBJECTIVES: In addition to neuronal loss in striatum and cerebral cortex that characterizes Huntington's disease (HD), hypothalamic atrophy has also been found only in certain areas, probably not including dopaminergic functions. METHODS: We assessed the reactivity of the hypothalamus-pituitary dopaminergic system by measuring the acute prolactin (PRL) responses to 5 mg i.m. haloperidol in male and female HD patients and in female subjects with expanded CAG repeats in the Huntington gene before disease onset, as well as in a group of healthy males. RESULTS: The responses of the male patients were similar to those of a group of male healthy volunteers. Females gave higher PRL responses, with no differences in the response patterns of female patients and females at risk for HD. PRL elevations were not related to severity of illness, or to presence of dementia, depression, or psychotic features. CONCLUSIONS: The results implicate a normal dopaminergic input from hypothalamus to pituitary and preserved pituitary dopamine receptors, indicating that hypothalamic atrophy in HD does not affect mechanisms involved in PRL secretion by haloperidol. PMID- 20588236 TI - Neonatal and maternal concentrations of hydroxil radical and total antioxidant system: protective role of placenta against fetal oxidative stress. AB - BACKGROUND: Reactive oxygen species (ROS) may cause peroxydation of lipids, proteins and deoxyribonucleic acids with subsequent cell damage. The hydroxyl radical (OH*) represents a measure of global oxidative stress. Hydroxyl radicals are short-lived; they form an important part of radical chemistry nonetheless. The measure of total antioxidant system (TAS) can give useful information about the extent of defence capable of counteracting the oxidative damage. Pregnancy is an important condition that favors oxidative stress in the fetus. Clinical studies indicate a protective mechanism against O2 toxicity in the human feto placental unit. AIM: This study reports the OH* and TAS concentrations in mother and fetus at birth to evaluate the role of the placenta against fetal oxidative stress. METHODS: Blood samples were collected at delivery from 45 healthy women at term and from their newborns. The maternal and neonatal OH* and TAS concentrations were compared by paired Student t-test. RESULTS: OH* was higher in maternal blood than in cord blood (573.75+/- 170.0 UCarr/l vs 40.08+/-33.37 UCarr/l) (p<0.01); TAS concentrations did not differ between the two groups (1.11+/-0.09 mmol/l vs 1.17+/-0.12 mmol/l). Multiple regression analyses: maternal and neonatal OH* decreases with maternal age; only maternal TAS and OH* are related to gestational age in a nonlinear fashion. Female infants showed higher values of maternal and neonatal TAS as compared to male infants. CONCLUSION: TA protective role of the placenta against oxidative damage is in keeping with a large enough gradient of ROS (between mother and fetus) and the passage of TAS from mother to fetus. PMID- 20588237 TI - Melatonin restores the basal level of lipid peroxidation in rat tissues exposed to potassium bromate in vitro. AB - OBJECTIVE: Potassium bromate (KBrO3) is a prooxidant and carcinogen. Melatonin is a highly effective antioxidant. Indole-3-propionic acid (IPA; indole substance) and propylothiouracil (PTU; antithyroid drug) reveal some antioxidative effects. The aim of the study was to evaluate KBrO3-induced lipid peroxidation (LPO) in vitro in tissues collected from control or melatonin-treated rats, and to compare potential preventive effects of melatonin, IPA and PTU. MATERIALS AND METHODS: Kidney, liver and lung homogenates from either control or melatonin-pretreated rats (0.0645 mmol/kg b.w., i.p., twice daily, 10 days) were incubated in the presence of KBrO3 (0.1, 0.5, 1.0, 2.5, 5.0, 10.0 mM). Then, control lung homogenates were incubated with KBrO3 (10.0 mM) together with melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or with IPA or with PTU. LPO products (malondialdehyde+4-hydroxyalkenals) were measured spectrophotometrically. RESULTS: Melatonin injections prevented KBrO3-induced LPO in lung homogenates. Melatonin, IPA and PTU, used in vitro, reduced KBrO3-induced LPO in control lungs. Unexpectedly, KBrO3 caused a concentration-dependent decrease in LPO in liver and kidney homogenates from control but not from melatonin-treated rats. CONCLUSIONS: Potassium bromate-induced LPO in the rat lung homogenates suggests that the lung may be the target for this carcinogen. An exposure of organisms to melatonin decreases tissue sensitivity to KBrO3-induced damage, possibly by restoring the oxidative balance. PMID- 20588238 TI - Maternal treatment of rats with the new pyridoindole antioxidant during pregnacy and lactation resulting in improved offspring hippocampal resistance to ischemia in vitro. AB - OBJECTIVE: Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of protective mechanisms, etc. Further, the developing brain may be damaged by intrauterine ischemia or by ischemia in newborns complicated by perinatal asphyxia. There is an effort to find agents with neuroprotective effect on the developing brain. The aim was to study the effect of the new pyridoindole antioxidant SMe1EC2 on the resistance of offspring hippocampus exposed to ischemia in vitro after treatment of mothers. MATERIALS AND METHODS: The electrically evoked responses were determined by extracellular recording from offspring hippocampal slices. The effect of oral treatment of rats with SMe1EC2 over 18 consecutive days, from day 15 of gestation to day 10 post partum (PP) was analyzed in the model of ischemia in vitro measured on the hippocampus of 21-day-old pups, with focus on neuronal function recovery in reoxygenation. RESULTS: Increased recovery of neuronal response was found at the end of 20-min reoxygenation in offspring hippocampal slices exposed to 10-min hypoxia/hypoglycemia from rats whose mothers were treated with the dose of 50 and 250 mg/kg of SMe1EC2, compared to control offspring slices (mothers received vehicle over the same time). CONCLUSIONS: The increased offspring hippocampus resistance to hypoxia/hypoglycemia due to 18-day maternal treatment with SMe1EC2 might have been obtained via the transplacental way as well as in the neonatal period via breast milk, skin and saliva. The manifested neuroprotective effect of SMe1EC2 on the developing brain might find exploitation during risk pregnancy and delivery. PMID- 20588239 TI - Leptin/adiponectin ratio in obese women with and without binge eating disorder. AB - BACKGROUND: Adipose tissue-derived hormones are involved in the pathophysiology of eating disorders and other mental disorders. Studies have suggested that the serum leptin/adiponectin ratio is highly correlated with BMI. Furthermore, it is associated with a number of metabolic processes and inflammatory markers that are involved in obesity and mental disorders, such as the physiopathology of binge eating disorder (BED). We investigated whether variations in leptin and adiponectin serum concentrations differed between adult women with and without BED before and after a meal. METHODS: The study group was composed of 8 normal weight women (20-25 kg/m2) without BED, 8 obese women (>/=30 kg/m2) with BED, and 7 obese women without BED (non-BED). Blood samples were collected before and after the consumption of a meal composed of 55% carbohydrates, 15% protein, and 30% lipids. RESULTS: Body mass index (p<0.0001), leptin (p<0.0001) and the leptin/adiponectin ratio (p<0.0001) were higher in obese non-BED women than in obese BED and normal weight groups. Adiponectin (p=0.01) concentrations were lower in the obese BED group than in the other groups before and after the meal. CONCLUSIONS: The hypoadiponectinemia followed by the altered levels of leptin in obese BED woman may predispose these subjects to an inadequate energy balance, which could promote weight gain and an increased food intake in woman that may contribute to obesity and binge eating in these subjects. PMID- 20588240 TI - Importance of screening serological examination of umbilical blood and the blood of the mother for timely diagnosis of congenital toxoplasmosis and toxocariasis. AB - OBJECTIVE: Parasitic diseases, particularly the congenital form of toxoplasmosis, can negatively affect the mortality and morbidity of newborns and infants. METHODS: The authors examined 152 samples of umbilical blood in 152 women who had experienced premature delivery with or without PROM. The samples were examined for the titre of antibodies - the CFR, levels of immunoglobulins IgA and IGM (toxoplasmosis) and for titres of antibodies against toxocariasis. RESULTS: No presence of IGM was demonstrated in association with the congenital form of toxoplasmosis. The values of titres of antibodies against toxocariasis were negative. There was only one case of a titre in a newborn higher than that in the mother. There was no clinical manifestation of the disease. CONCLUSION: In spite of the negative result, the authors point out the possibility of a timely diagnosis of these parasitic diseases. PMID- 20588241 TI - Hyperreactio luteinalis in spontaneous singleton pregnancy. AB - A case of a pregnant woman with bilateral cystic ovaries diagnosed in the 12th week of gestation is presented. The successful outcome of pregnancy with hyperreactio luteinalis, which spontaneously resolved in the 3rd trimester and the importance of a differential diagnosis of an abdominal mass during pregnancy to avoid unnecessary surgery is demonstrated. PMID- 20588242 TI - High prevalence of obesity in patients with non-functioning adrenal incidentalomas. AB - OBJECTIVE: The influence of obesity on cancer development has been proven for numerous tumours. In contrast, the association between obesity and non-secreting adrenal incidentaloma has never been proven. Therefore, the aim of this study was to investigate this relationship in a large sample of patients. METHODS: 143 patients with benign non-secreting adrenal incidentalomas treated in the Department of Endocrinology at the Poznan University of Medical Sciences between the years 2000-2007 were examined. To rule out subclinical hyperfunctioning lesions, serum dehydroepiandrosterone sulphate, cortisol (8 am, 6 pm, and after 1 mg dexamethasone suppression), sodium and potassium, along with concentrations of sodium, potassium, vanillylmandelic acid, metanephrine and normetanephrine in 24 hour urine collection were determined. Radiological evaluation included computed tomography and/or magnetic resonance imaging. Only non-secreting lesions and those of benign radiologic appearance were considered. The patients body mass index was compared to that of the general population of Poland and the Western Poland Region of Wielkopolska. RESULTS: The average body mass index of our patients was 28.77 kg/m2 (SD=4.71), with a 40% prevalence of obesity in the study group. One-proportion z-test showed a statistically significantly higher prevalence of obesity as compared to the general population of Poland and Wielkopolska (40% vs 12.5%, p<0.005); the results were similar for the whole cohort, and for each gender separately. CONCLUSIONS: This clinical research study demonstrates a strong association between obesity and incidentally discovered non functioning adrenal tumours. PMID- 20588243 TI - Glycoxidative and nitrosative stress in kidney of experimental diabetic rats: effects of the prydoindole antioxidant stobadine. AB - OBJECTIVES: Recent basic research and clinical data have provided new insights into the role of glycoxidative and nitrosative stresses (both oxidative stress) in diabetic complications, such as diabetic nephropathy, suggesting a different and innovative approach to antioxidant therapy. In streptozotocin-induced diabetic rat kidney, the present study investigated the effects of the synthetic pyridoindole antioxidant stobadine (STB) on renal total antioxidant potential (AOP) and protein oxidation parameters such as protein carbonyl content (PCC), advanced oxidation protein products (AOPPs) and nitrotyrosine (NT), a marker specific for protein modification by peroxynitrite. MATERIALS AND METHODS: Wistar Albino rats were divided into two groups: normal and streptozotocin-induced diabetic rats. Each group of the animals was further divided into two groups: untreated and treated with stobadine (24.7 mg/kg) during 16 weeks daily by oral gavage. RESULTS: The renal tissue AOP and the levels of AOPPs, PCC and NT were increased in diabetic rats compared with the untreated control animals. Furthermore, stobadine treatment significantly decreased protein carbonylation and AOPPs but not NT. CONCLUSIONS: These findings indicate that STB is an antioxidant factor which can improve glycoxidative stress markers in kidney, while it has no effect on protein nitrosylation. PMID- 20588244 TI - Germ cell tumor presenting as sellar mass with suprasellar extension and long history of hypopituitarism. AB - OBJECTIVE: Primary central nervous system germ cell tumors are rare neoplasms usually located in the pineal and/or suprasellar region. Pure germinomas do not usually secrete beta-human chorionic gonadotropin hormone (beta-HCG) or alpha fetoprotein (AFP) and diagnosis is made a few weeks or months after beginning of symptoms. CASE: Here we report a case of a pure germinoma in a 20 year-old woman presenting as a sellar mass with suprasellar extension, abnormal serum beta-HCG and a long history of polyuria and polydipsia (4 years), that was initially diagnosed as a pituitary macroadenoma. CONCLUSION: This presentation highlights the importance of thinking in alternative diagnosis to pituitary adenoma when diabetes insipidus is the initial symptom. PMID- 20588245 TI - External hydrogen peroxide is not indispensable for experimental induction of lipid peroxidation via Fenton reaction in porcine ovary homogenates. AB - OBJECTIVE: Substrates of Fenton reaction (Fe(2+)+H(2)O(2)-->Fe(3+)+*OH+OH-) may be used to experimentally induce oxidative damage to macromolecules. The study aimed at evaluating effects of Fe(2+) and/or H(2)O(2) on lipid peroxidation in porcine ovary homogenates. MATERIALS AND METHODS: Ovary homogenates were incubated in the presence of either H2O2 (100, 50, 25, 10, 5.0, 2.5, 1.0, 0.5, 0.25, 0.01, 0.001 mM) or FeSO(4) (Fe2+) (300, 150, 75, 30, 15, 7.5, 3.0, 1.5, 0.75 microM), or of those two factors used together: Fe(2+) (30 microM) plus H(2)O(2) (concentrations as above), or H(2)O(2) (0.5 mM) plus Fe(2+) (concentrations as above). The concentration of malondialdehyde+4-hydroxyalkenals constituted the lipid peroxidation index. RESULTS: H(2)O(2) alone did not affect lipid peroxidation in porcine ovary homogenates at all, whereas Fe(2+) (300, 150, 75, 30, and 15 microM) alone increased lipid peroxidation in a concentration dependent manner. When Fe(2+) and H(2)O(2) were applied together, lipid peroxidation increased significantly without any concentration related effect of H(2)O(2), but with a clear concentration dependent effect of Fe(2+); the damaging effect of Fe(2+), used together with H(2)O(2), was the same as the one, obtained after Fe(2+) was applied alone. CONCLUSIONS: In conclusion, external H(2)O(2) is not indispensable for experimental induction of lipid peroxidation by Fenton reaction in porcine ovary homogenates. PMID- 20588246 TI - Evaluation of the association between the CYP19 Tetranucleotide (TTTA)n polymorphism and polycystic ovarian syndrome(PCOS) in Han Chinese women. AB - OBJECTIVE: Evidence indicates that the CYP19 gene is a positional and functional candidate for genetic study in polycystic ovarian syndrome (PCOS). The present study aims to evaluate the association between tetranucleotide TTTA repeat polymorphism in the CYP19 gene and PCOS among Han Chinese women. METHODS: Clinical materials employed in this study consist of 123 patients with PCOS and 113 healthy controls. The CYP19 tetranucleotide TTTA repeat polymorphism was genotyped with a protocol of PCR and fluorescent capillary electrophoresis. RESULTS: Common allele of the CYP19 tetranucleotide TTTA repeat polymorphism in this population of Han Chinese women was 11R. The frequency of 11R in PCOS was lower than in the control subjects (34.55% vs 42.92%, p=0.046). The carriers with allele 11R in PCOS had decreased CHO (5.00+/-0.63 vs 6.14+/-0.85 mmol/L, p=0.012). The carriers with allele 7R-TCT in PCOS had increased CHO (5.96+/-0.83 vs 5.08+/-0.65 mmol/L, p=0.027) and LDL (5.11+/-0.77 vs 4.31+/-0.66 mmol/L, p=0.014) compared to the patients carrying other alleles. CONCLUSIONS: The most common allele of the tetranucleotide TTTA repeat polymorphism in the forth intron of CYP19 gene in Han Chinese women is 11R, which was different with the previous study in European Caucasians. Allele 11R may be associated with PCOS in the population of Han Chinese women, and it may refrain from the hypercholesteremia of PCOS. Allele 7R-TCT may be related to the lipid metabolism of PCOS. This CYP19 tetranucleotide TTTA repeat polymorphism is an ethnic and racial variant and moderately contributes to the pathogenesis of PCOS in the population of Han Chinese women. PMID- 20588247 TI - Effect of mitogen lectin on lymphocyte or brain cortex cell activation. AB - OBJECTIVES: We studied a) mitogen lectin (PHA) evoked changes of Na+/K+-ATPase activity in functionally different lymphocytes or brain cortex cells and b) quantitative relationship between PHA- evoked early enzyme activation and late lymphocyte proliferation were analyzed. MATERIALS AND METHODS: We performed biochemical analyses of Pi released from ATP by Na+/K+-ATPase activity. Lymphocyte proliferation was assayed by 3H-thymidine incorporation. RESULTS: We demonstrated PHA stimulated Na+/K+-ATPase activity of mouse spleen lymphocytes or freshly isolated brain cortex cells. Besides this, we estimated high stimulation of Na+/K+-ATPase activity and subsequent late 3H-thymidine incorporation into pig lymphocytes as both PHA dose and K+ ion concentration dependent. CONCLUSIONS: Thus, early PHA dose-dependent stimulation of Na+/K+-ATPase activity is a more general response in different animal species and functionally different cells. We measured both cell type- and PHA-dose dependent enzyme activity stimulation. We can suggest that intensity of early PHA induced Na+/K+-ATPase activation could be in relationship to subsequent elevated level of T lymphocyte proliferation. The Na+/K+-ATPase can be a part of mitogen lectin evoked signal transduction mechanisms. PMID- 20588248 TI - Distribution of ghrelin-producing cells in stomach and the effects of ghrelin administration in the house musk shrew (Suncus murinus). AB - OBJECTIVE: To investigate the distribution of ghrelin, an important appetite regulatory factor related to obesity, in the stomach of Suncus murinus, and attempted to elucidate the ghrelin-mediated regulatory effect in this animal. METHODS: The stomachs of Suncus murinus were divided into 5 sections, cardia, fundus, greater curvature, lesser curvature, and pylorus, for investigating the ghrelin-producing cells by immunohistochemistry and Western blotting. Then Suncus murinus were randomized into two groups with ghrelin intraperitoneal injection (ghrelin-ip group) and saline intraperitoneal injection (control group), respectively. The effects of food intake and body weight were measured, and furthermore, the distribution of ghrelin in stomach was also investigated by immunohistochemistry and Western blotting. RESULTS: The immunolocalization and protein levels of ghrelin differed significantly in different regions of the stomach of Suncus murinus. Furthermore, ghrelin administration did not change the rate of food intake, but resulted in an increase in body weight compared with the control group. In this study, we elucidated the distribution of ghrelin-producing cells in the stomach of Suncus murinus in detail for the first time. Ghrelin intraperitoneal administration was found to induce an increase in body weight without changing food intake in this species. CONCLUSION: Our study implied ghrelin showed a different regulatory function in Suncus murinus from other species. It is considered that ghrelin may be associated with obesity-resistance phenomenon in Suncus murinus. PMID- 20588249 TI - Complication rates in the second and third trimester of spontaneous twin pregnancies and twin pregnancies after in vitro fertilization. AB - BACKGROUND: Most authors agree that the twin pregnancies have a higher risk of complications compared to singleton pregnancies. However, there is no unanimity as to whether the risk of complications in twin pregnancies resulting from in vitro fertilization is higher than in twin pregnancies resulting from spontaneous conception. OBJECTIVE: The aim of this study was to estimate the frequency rates of complications in the second and third trimester of dichorionic-diamniotic twin pregnancies resulting from IVF (group I) compared to dichorionic-diamniotic and monochorionic-diamniotic twin pregnancies resulting from spontaneous conception (group II and III). RESULTS: The rate of cesarean section and cervical cerclage was significantly higher in the group I. Polyhydramnios occurred less frequently in group I than in group III. The discordant growth of fetuses occurred significantly more frequently in the group I. The frequency of other complications did not differ in the studied groups. The Apgar score was similar in the group I and II but significantly lower in the group III compared to the group I. CONCLUSIONS: 1) The frequency of complications in twin pregnancies after IVF is similar to those in the twin pregnancies conceived spontaneously. 2) In the twin pregnancies after IVF it is necessary to expect only a higher frequency of caesarean sections, cervical incompetence and a discordant growth of the twins when comparing with twin pregnancies conceived spontaneously. 3) In the twin pregnancies after IVF the intrauterine fetal demise and polyhydramnios occurred less frequently than in monochorionic-diamniotic pregnancies after spontaneous conception. PMID- 20588250 TI - Cognitive disorders in type 2 diabetic patients with recognized depression. AB - OBJECTIVES: The most important factors in the pathogenesis of cognitive disorders in diabetes mellitus (DM) are metabolic changes directly caused by hyperglycemia. Impairment of cognitive function is accompanied by a decrease in cerebral insulin. Insulin improves cognitive processes, including somatosensoric cognitive functions. Cognitive disorders are especially pronounced if diabetic patients suffer also from depression. MATERIAL AND METHODS: The evaluation of cognitive functions, especially sensomotoric skills were obtained from three study groups (aged 37-52 years): 30 healthy subjects, 40 diabetic patients with clinically documented depression and 30 depressive patients without DM. The sensomotoric skills were carried out using a SPS-2001E apparatus - a computer working stress simulator. The examination with Beck Depression Inventory (BDI) were also performed in all the investigated persons. RESULTS: Sensomotoric skills investigation revealed slight cognitive disorders in the early stages DM (subgroup IA) and its intensification according to increasing BDI scores and HbA1c blood concentration (from subgroup IA to IC). Intensification of sensomotoric cognitive disorders was significantly higher (p<0.001) in the depressive patients with DM (group I), than in these without DM (group III). CONCLUSIONS: The obtained results suggest that coincidence of aggravating factors, such as depression and metabolic disorders in DM, may cause mutual interactions leading to premature and more intense cognitive impairment. The method proposed by the authors may serve as a screening examination in early diagnosis of CNS disorders reflected by somatosensoric cognitive disorders. The presented work indicates importance of sensomotoric skills investigation for the early diagnosis of the nervous system damage related to DM. PMID- 20588251 TI - Activities of respiratory chain complexes and citrate synthase influenced by pharmacologically different antidepressants and mood stabilizers. AB - OBJECTIVE: Mitochondrial dysfunctions, impaired bioenergetics and dysfunction of neurotrophins are included in many neurodegenerative and psychiatric diseases. We investigated in vitro effects of pharmacologically different antidepressants and mood stabilizers on mitochondrial enzymes to discover, which mitochondrial functions could be involved in pathophysiology of mood disorders. METHODS: In vitro effects of eight pharmacologically different antidepressants (desipramine, amitriptyline, imipramine, citalopram, venlafaxine, mirtazapine, tianeptine, and moclobemide) and three mood stabilizers (lithium, valproate, and olanzapine) on the activities of mitochondrial enzymes (citrate synthase and enzymes in electron transport chain, i.e. complexes I, II, IV) were measured in crude mitochondrial fraction isolated from pig brain. RESULTS: Most of the antidepressants and mood stabilizers inhibited the activities of respiratory electron transport chain complexes, complexes I and IV were the most affected. Statistically significant decrease of the complex I activity was caused by desipramine, amitriptyline, imipramine, citalopram, mirtazapine, valproate and olanzapine. Complex II was significantly inhibited only by amitriptyline, imipramine, citalopram and venlafaxine. Complex IV was significantly inhibited by all tested drugs except for citalopram and moclobemide. Unchanged or slightly increased citrate synthase activity was observed; significant activation of the enzyme was observed after citalopram, tianeptine and olanzapine. CONCLUSIONS: Our results indicate that antidepressants may act generally as inhibitors of complex I and complex IV of the electron transport chain. These mitochondrial enzymes are suggested as proper candidates in searching of new biological markers of mood disorders, targets of new antidepressants or predictors of response to pharmacotherapy. PMID- 20588252 TI - The function of classical and alternative non-homologous end-joining pathways in the fusion of dysfunctional telomeres. AB - Repair of DNA double-stranded breaks (DSBs) is crucial for the maintenance of genome stability. DSBs are repaired by either error prone non-homologous end joining (NHEJ) or error-free homologous recombination. NHEJ precedes either by a classic, Lig4-dependent process (C-NHEJ) or an alternative, Lig4-independent one (A-NHEJ). Dysfunctional telomeres arising either through natural attrition due to telomerase deficiency or by removal of telomere-binding proteins are recognized as DSBs. In this report, we studied which end-joining pathways are required to join dysfunctional telomeres. In agreement with earlier studies, depletion of Trf2 resulted in end-to-end chromosome fusions mediated by the C-NHEJ pathway. In contrast, removal of Tpp1-Pot1a/b initiated robust chromosome fusions that are mediated by A-NHEJ. C-NHEJ is also dispensable for the fusion of naturally shortened telomeres. Our results reveal that telomeres engage distinct DNA repair pathways depending on how they are rendered dysfunctional, and that A-NHEJ is a major pathway to process dysfunctional telomeres. PMID- 20588253 TI - CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response. AB - The extracellular signal-regulated kinase (ERK) pathway is an important signalling pathway that regulates a large number of cellular processes, including proliferation, differentiation and gene expression. Hyperosmotic stress activates the ERK pathway, whereas little is known about the regulatory mechanisms and physiological functions of ERK activation in hyperosmotic response. Here, we show that MAPK/ERK kinase kinase 2 (MEKK2), a member of the MAPKKK family, mediated the specific and transient activation of ERK, which was required for the induction of aquaporin 1 (AQP1) and AQP5 gene expression in response to hyperosmotic stress. Moreover, we identified the E3 ubiquitin ligase carboxyl terminus of Hsc70-interacting protein (CHIP) as a binding partner of MEKK2. Depletion of CHIP by small-interference RNA or gene targeting attenuated the degradation of MEKK2 and prolonged the ERK activity. Interestingly, hyperosmolality-induced gene expression of AQP1 and AQP5 was suppressed by CHIP depletion and was reversed by inhibition of the prolonged phase of ERK activity. These findings show that transient activation of the ERK pathway, which depends not only on MEKK2 activation, but also on CHIP-dependent MEKK2 degradation, is crucial for proper gene expression in hyperosmotic stress response. PMID- 20588254 TI - Recognition of the amber UAG stop codon by release factor RF1. AB - We report the crystal structure of a termination complex containing release factor RF1 bound to the 70S ribosome in response to an amber (UAG) codon at 3.6-A resolution. The amber codon is recognized in the 30S subunit-decoding centre directly by conserved elements of domain 2 of RF1, including T186 of the PVT motif. Together with earlier structures, the mechanisms of recognition of all three stop codons by release factors RF1 and RF2 can now be described. Our structure confirms that the backbone amide of Q230 of the universally conserved GGQ motif is positioned to contribute directly to the catalysis of the peptidyl tRNA hydrolysis reaction through stabilization of the leaving group and/or transition state. We also observe synthetic-negative interactions between mutations in the switch loop of RF1 and in helix 69 of 23S rRNA, revealing that these structural features interact functionally in the termination process. These findings are consistent with our proposal that structural rearrangements of RF1 and RF2 are critical to accurate translation termination. PMID- 20588256 TI - Statistical issues in longitudinal data analysis for treatment efficacy studies in the biomedical sciences. AB - Longitudinally collected outcomes are increasingly common in cell biology and gene therapy research. In this article, we review the current practice of statistical analysis of longitudinal data in these fields, and recommend the "best performing" statistical method among those available in most statistical packages. A survey of papers published in Molecular Therapy indicates that longitudinal data are only properly analyzed in a small fraction of articles, and the most popular approach was analyzing each measurement time point data separately using an analysis of variance (ANOVA) model with Tukey's post hoc tests. We show that first, such cross-sectional ANOVA approach does not utilize all the power that the longitudinal design of a study provides, and second, Tukey's post hoc tests applied at each measurement time separately could result in a false positivity rate as high as 30% using a simulation study. We recommend mixed effects model analysis instead. We also discuss the complexities of multiple comparison adjustment in the post hoc testing that result from within experimental unit correlation existing in longitudinal data. We recommend resampling as a method that readily adjusts the post hoc testing to be limited to only interesting comparisons and thereby avoids unduly sacrificing the power. PMID- 20588255 TI - MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. AB - MDM2 is a key regulator of the p53 tumor suppressor acting primarily as an E3 ubiquitin ligase to promote its degradation. MDM2 also inhibits p53 transcriptional activity by recruiting histone deacetylase and corepressors to p53. Here, we show that immunopurified MDM2 complexes have significant histone H3 K9 methyltransferase activity. The histone methyltransferases SUV39H1 and EHMT1 bind specifically to MDM2 but not to its homolog MDMX. MDM2 mediates formation of p53-SUV39H1/EHMT1 complex capable of methylating H3-K9 in vitro and on p53 target promoters in vivo. Furthermore, MDM2 promotes EHMT1-mediated p53 methylation at K373. Knockdown of SUV39H1 and EHMT1 increases p53 activity during stress response without affecting p53 levels, whereas their overexpression inhibits p53 in an MDM2-dependent manner. The p53 activator ARF inhibits SUV39H1 and EHMT1 binding to MDM2 and reduces MDM2-associated methyltransferase activity. These results suggest that MDM2-dependent recruitment of methyltransferases is a novel mechanism of p53 regulation through methylation of both p53 itself and histone H3 at target promoters. PMID- 20588257 TI - Rescue of a dystrophin-like protein by exon skipping in vivo restores GABAA receptor clustering in the hippocampus of the mdx mouse. AB - Dystrophin, the cytoskeletal protein whose defect is responsible for Duchenne muscular dystrophy (DMD), is normally expressed in both muscles and brain. Genetic loss of brain dystrophin in the mdx mouse model of DMD reduces the capacity for type A gamma-aminobutyric acid (GABA(A))-receptor clustering in central inhibitory synapses, which is thought to be a main molecular defect leading to brain and cognitive alterations in this syndrome. U7 small nuclear RNAs modified to encode antisense sequences and expressed from recombinant adeno associated viral (rAAV) vectors have proven efficient after intramuscular injection to induce skipping of the mutated exon 23 and rescue expression of a functional dystrophin-like product in muscle tissues of mdx mice in vivo. Here, we report that intrahippocampal injection of a single dose of rAAV2/1-U7 can rescue substantial levels of brain dystrophin expression (15-25%) in mdx mice for months. This is sufficient to completely restore GABA(A)-receptor clustering in pyramidal and dendritic layers of CA1 hippocampus, suggesting exon-skipping strategies offer the prospect to investigate and correct both brain and muscle alterations in DMD. This provides new evidence that in the adult brain dystrophin is critical for the control of GABA(A)-receptor clustering, which may have an important role in activity-dependent synaptic plasticity in hippocampal circuits. PMID- 20588258 TI - A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors. AB - DNA methylation may restrict the activity of gene transfer vectors due to inadvertent silencing. In P19 embryonic carcinoma cells in vitro, we found that transgene expression regulated by the SFFV LTR and EF1 alpha promoter declined rapidly within 16 days, but for A2UCOE derived from the human HNRPA2B1-CBX3 housekeeping gene locus, remained completely stable. Silencing correlated with extensive epigenetic methylation of CpG sites, whereas the A2UCOE was almost completely resistant. Linking of the A2UCOE upstream of the SFFV LTR protected this element from both DNA methylation and silencing. Analysis of engrafted hematopoietic cells in vivo transduced with the same vectors revealed a similar pattern. The A2UCOE displayed little or no methylation in either primary or secondary graft recipients, and gene expression profiles were highly conserved between the two groups. These studies provide convincing evidence that DNA methylation plays a direct role in regulating self-inactivating (SIN) lentiviral transgene expression, and that the stability of expression from the A2UCOE is, at least in part, due to methylation resistance. The A2UCOE therefore has considerable utility for gene therapy applications where reliable and sustained gene expression is desirable. PMID- 20588259 TI - Bone marrow mesenchymal stem cells loaded with an oncolytic adenovirus suppress the anti-adenoviral immune response in the cotton rat model. AB - Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow-derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-gamma (IFN-gamma) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response. PMID- 20588260 TI - Therapeutic effect of sodium iodide symporter gene therapy combined with external beam radiotherapy and targeted drugs that inhibit DNA repair. AB - Adenoviral (AdV) transfer of sodium iodide symporter (NIS) gene has translational potential, but relatively low levels of transduction and subsequent radioisotope uptake limit the efficacy of the approach. In previous studies, we showed that combining NIS gene delivery with external beam radiotherapy (EBRT) and DNA damage repair inhibitors increased viral gene expression and radioiodide uptake. Here, we report the therapeutic efficacy of this strategy. An adenovirus expressing NIS from a telomerase promoter (Ad-hTR-NIS) was cytotoxic combined with relatively high-dose (50 microCi) (131)I therapy and enhanced the efficacy of EBRT combined with low-dose (10 and 25 microCi) (131)I therapy in colorectal and head and neck cancer cells. Combining this approach with ataxia-telangiectasia mutated (ATM) or DNA-dependent protein kinase (DNA-PK) inhibition caused maintenance of double stranded DNA breaks (DSBs) at 24 hours and increased cytotoxicity on clonogenic assay. When the triplet of NIS-mediated (131)I therapy, EBRT, and DNA-PKi was used in vivo, 90% of mice were tumor-free at 5 weeks. Acute radiation toxicity in the EBRT field was not exacerbated. In contrast, DNA-PKi did not enhance the therapeutic efficacy of EBRT plus adenovirus-mediated HSVtk/ganciclovir (GCV). Therefore, combining NIS gene therapy and EBRT represents an ideal strategy to exploit the therapeutic benefits of novel radiosensitizers. PMID- 20588261 TI - Proteinase-activated receptor-2 in the pathogenesis of gastroesophageal reflux disease. AB - OBJECTIVES: The proteinase-activated receptor-2 (PAR-2) is activated by serine proteases and has been demonstrated to induce proinflammatory and neuroinflammatory effects. It is considered to alter transepithelial resistance and mediates visceral hypersensitivity. This study aimed to evaluate the expression of PAR-2 in human esophageal mucosa of patients with gastroesophageal reflux disease (GERD) in relation to mucosal alterations. METHODS: The study included 123 patients with GERD stratified to erosive reflux disease (n=50), non erosive reflux disease (n=46), and reflux-negative patients as controls (n=27). Endoscopic and histopathological characterization was performed according to the Los Angeles classification and modified Ismail-Beigi criteria, respectively. PAR 2 expression was analyzed by quantitative reverse transcription (RT)-PCR and immunohistochemistry. The gene expression levels of interleukin (IL)-8 were determined by quantitative RT-PCR and correlated to PAR-2 expression in each patient. Performing in vitro studies, esophageal squamous cell lines (KYSE 150, KYSE 450) were incubated, adjusted to different pH (7.0, 6.0, and 5.0), and exposed to bile acids and PAR-2-activation peptide (SLIGKV-NH(2)). RESULTS: PAR-2 gene expression was 7- to 10-fold upregulated (P<0.0001) in the mucosa of patients with GERD and correlated positively with IL-8 expression and with histomorphological alterations (dilated intercellular spaces, papillary elongation, basal cell hyperplasia (BCH); P<0.01). Immunohistochemistry showed an intense staining of PAR-2 throughout all epithelial layers in patients with GERD compared with controls (P=0.0005). In vitro studies revealed a 1.5- to 20-fold induction of PAR-2 gene expression in esophageal squamous cells by acidified medium (P<0.01), but not by additional bile acids. The activation of PAR-2 leads to expression and secretion of IL-8. CONCLUSIONS: This study provides evidence of the functional importance of PAR-2-mediated pathways in the pathogenesis of GERD and GERD-associated mucosal alterations and inflammatory changes. PMID- 20588263 TI - Long-term esophageal cancer risk in patients with primary achalasia: a prospective study. AB - OBJECTIVES: Achalasia patients are considered at increased risk for esophageal cancer, but the reported relative risks vary. Identification of this risk is relevant for patient management. We performed a prospective evaluation of the esophageal cancer risk in a large cohort of achalasia patients with long-term follow-up. METHODS: Between 1975 and 2006, all patients diagnosed with primary achalasia in our hospital were treated and followed by the same protocol. After graded pneumatic dilatation, all patients were offered a fixed surveillance protocol including gastrointestinal endoscopy with esophageal biopsy sampling. RESULTS: We surveyed a cohort of 448 achalasia patients (218 men, mean age 51 years at diagnosis, range 4-92 years) for a mean follow-up of 9.6 years (range 0.1-32). Overall, 15 (3.3%) patients (10 men) developed esophageal cancer (annual incidence 0.34 (95% confidence interval 0.20-0.56)). The mean age at cancer diagnosis was 71 years (range 36-90) after a mean of 11 years (range 2-23) following initial presentation, and a mean of 24 years (range 10-43) after symptom onset. The relative hazard rate of esophageal cancer was 28 (confidence interval 17-46) compared with an age- and sex-identical population in the same timeframe. Five patients received a potential curative treatment. CONCLUSIONS: Although the gastro-esophageal cancer risk in patients with longstanding achalasia is much higher than in the general population, the absolute risk is rather low. Despite structured endoscopical surveillance, most neoplastic lesions remain undetected until an advanced stage. Efforts should be made to identify high-risk groups and develop adequate surveillance strategies. PMID- 20588262 TI - Psychological dysfunction is associated with symptom severity but not disease etiology or degree of gastric retention in patients with gastroparesis. AB - OBJECTIVES: Gastroparesis patients may have associated psychological distress. This study aimed to measure depression and anxiety in gastroparesis in relation to disease severity, etiology, and gastric retention. METHODS: Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scores for state (Y1) and trait (Y2) anxiety were obtained from 299 gastroparesis patients from 6 centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium. Severity was investigator graded as grades 1, 2, or 3 and patient reported by Gastroparesis Cardinal Symptom Index (GCSI) scores. Antiemetic/prokinetic medication use, anxiolytic and antidepressant medication use, supplemental feedings, and hospitalizations were recorded. BDI, Y1, and Y2 scores were compared in diabetic vs. idiopathic etiologies and mild (<=20%) vs. moderate (>20-35%) vs. severe (>35-50%) vs. very severe (>50%) gastric retention at 4 h. RESULTS: BDI, Y1, and Y2 scores were greater with increasing degrees of investigator-rated gastroparesis severity (P<0.05). BDI, Y1, and Y2 scores were higher for GCSI >3.1 vs. <=3.1 (P<0.05). Antiemetic and prokinetic use and >=6 hospitalizations/year were more common with BDI >=20 vs. <20 (P<0.05). Anxiolytic use was more common with Y1>=46; antidepressant use and >=6 hospitalizations/year were more common with Y2>=44 (P<0.05). BDI, Y1, and Y2 scores were not different in diabetic and idiopathic gastroparesis and did not relate to degree of gastric retention. On logistic regression, GCSI >3.1 was associated with BDI >=20 and Y1>=46; antiemetic/prokinetic use was associated with BDI>=20; anxiolytic use was associated with Y1>=46; and antidepressant use was associated with Y2>=44. CONCLUSIONS: Higher depression and anxiety scores are associated with gastroparesis severity on investigator- and patient-reported assessments. Psychological dysfunction does not vary by etiology or degree of gastric retention. Psychological features should be considered in managing gastroparesis. PMID- 20588264 TI - The inflammatory bowel diseases and ambient air pollution: a novel association. AB - OBJECTIVES: The inflammatory bowel diseases (IBDs) emerged after industrialization. We studied whether ambient air pollution levels were associated with the incidence of IBD. METHODS: The health improvement network (THIN) database in the United Kingdom was used to identify incident cases of Crohn's disease (n=367) or ulcerative colitis (n=591), and age- and sex-matched controls. Conditional logistic regression analyses assessed whether IBD patients were more likely to live in areas of higher ambient concentrations of nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and particulate matter <10 MUm (PM(10)), as determined by using quintiles of concentrations, after adjusting for smoking, socioeconomic status, non-steroidal anti-inflammatory drugs (NSAIDs), and appendectomy. Stratified analyses investigated effects by age. RESULTS: Overall, NO(2), SO(2), and PM(10) were not associated with the risk of IBD. However, individuals <=23 years were more likely to be diagnosed with Crohn's disease if they lived in regions with NO(2) concentrations within the upper three quintiles (odds ratio (OR)=2.31; 95% confidence interval (CI)=1.25-4.28), after adjusting for confounders. Among these Crohn's disease patients, the adjusted OR increased linearly across quintile levels for NO(2) (P=0.02). Crohn's disease patients aged 44-57 years were less likely to live in regions of higher NO(2) (OR=0.56; 95% CI=0.33-0.95) and PM(10) (OR=0.48; 95% CI=0.29-0.80). Ulcerative colitis patients <=25 years (OR=2.00; 95% CI=1.08-3.72) were more likely to live in regions of higher SO(2); however, a dose-response effect was not observed. CONCLUSIONS: On the whole, air pollution exposure was not associated with the incidence of IBD. However, residential exposures to SO(2) and NO(2) may increase the risk of early onset ulcerative colitis and Crohn's disease, respectively. Future studies are needed to explore the age-specific effects of air pollution exposure on IBD risk. PMID- 20588265 TI - Nano-imaging of membrane topography affects interpretations in cell biology. PMID- 20588267 TI - Illuminating eukaryotic transcription start sites. PMID- 20588268 TI - Watching the fly brain in action. PMID- 20588269 TI - The inside view on plant growth. PMID- 20588270 TI - Discovery of serum biomarkers for pancreatic adenocarcinoma using proteomic analysis. AB - BACKGROUND AND AIMS: The serum/plasma proteome was explored for biomarkers to improve the diagnostic ability of CA19-9 in pancreatic adenocarcinoma (PC). METHODS: A Training Set of serum samples from 20 resectable and 18 stage IV PC patients, 54 disease controls (DCs) and 68 healthy volunteers (HVs) were analysed by surface-enhanced laser desorption and ionisation time-of-flight mass spectrometry (SELDI-TOF MS). The resulting protein panel was validated on 40 resectable PC, 21 DC and 19 HV plasma samples (Validation-1 Set) and further by ELISA on 33 resectable PC, 28 DC and 18 HV serum samples (Validation-2 Set). Diagnostic panels were derived using binary logistic regression incorporating internal cross-validation followed by receiver operating characteristic (ROC) analysis. RESULTS: A seven-protein panel from the training set PC vs DC and from PC vs HV samples gave the ROC area under the curve (AUC) of 0.90 and 0.90 compared with 0.87 and 0.91 for CA19-9. The AUC was greater (0.97 and 0.99, P<0.05) when CA19-9 was added to the panels and confirmed on the validation-1 samples. A simplified panel of apolipoprotein C-I (ApoC-I), apolipoprotein A-II (ApoA-II) and CA19-9 was tested on the validation-2 set by ELISA, in which the ROC AUC was greater than that of CA19-9 alone for PC vs DC (0.90 vs 0.84) and for PC vs HV (0.96 vs 0.90). CONCLUSIONS: A simplified diagnostic panel of CA19-9, ApoC-I and ApoA-II improves the diagnostic ability of CA19-9 alone and may have clinical utility. PMID- 20588271 TI - Comparison of discriminatory power and accuracy of three lung cancer risk models. AB - BACKGROUND: Three lung cancer (LC) models have recently been constructed to predict an individual's absolute risk of LC within a defined period. Given their potential application in prevention strategies, a comparison of their accuracy in an independent population is important. METHODS: We used data for 3197 patients with LC and 1703 cancer-free controls recruited to an ongoing case-control study at the Harvard School of Public Health and Massachusetts General Hospital. We estimated the 5-year LC risk for each risk model and compared the discriminatory power, accuracy, and clinical utility of these models. RESULTS: Overall, the Liverpool Lung Project (LLP) and Spitz models had comparable discriminatory power (0.69), whereas the Bach model had significantly lower power (0.66; P=0.02). Positive predictive values were highest with the Spitz models, whereas negative predictive values were highest with the LLP model. The Spitz and Bach models had lower sensitivity but better specificity than did the LLP model. CONCLUSION: We observed modest differences in discriminatory power among the three LC risk models, but discriminatory powers were moderate at best, highlighting the difficulty in developing effective risk models. PMID- 20588272 TI - The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy. AB - BACKGROUND: Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth. METHODS: The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250 mm(3)) were irradiated with 25 Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10 mg kg(-1)) once daily; RB6145 (75 mg kg(-1)) and tirapazamine (13 mg kg(-1)) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50% of controls exhibited detrimental signs of lung metastases. RESULTS: In total, 95% of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33%; P=0.0002) and RB6145 (60%; P=0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P<0.0001); RB6145, 1 (P<0.001), tirapazamine, 3 (P=0.007)). Positron emission tomography (PET) was evaluated as a non-invasive means of assessing metastatic development. Primary and metastatic KHT tumours showed robust uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG). Metastatic burden discernable by [(18)F]FDG PET correlated well with macroscopic and histological lung analysis. CONCLUSION: The hypoxia-selective cytotoxin NLCQ-1 controls metastatic disease and may be a successful adjuvant to radiotherapy in the clinical setting. PMID- 20588273 TI - A prospective epidemiological study of new incident GISTs during two consecutive years in Rhone Alpes region: incidence and molecular distribution of GIST in a European region. AB - BACKGROUND: Preliminary data indicate that the molecular epidemiology of localised gastrointestinal stromal tumour (GIST) may be different from that of advanced GIST. We sought to investigate the molecular epidemiology of sarcomas, including GIST, in the Rhone-Alpes region in France. PATIENTS AND METHODS: A prospective and exhaustive study in the Rhone-Alpes Region in France to assess the precise incidence of primary sarcomas with systematic centralised pathological review and molecular analysis was conducted for 2 consecutive years. RESULTS: Among 760 patients with a confirmed diagnosis of sarcoma, 131 (17%) had a GIST. The majority of patients had gastric primaries (61%). Mutational analysis could be performed in 106 tumour samples (74%), and 71 (67%) had exon 11 mutations. PDGFRA mutations were found in 16% of cases, which is twice as high as previously reported for advanced GIST. CONCLUSION: Data indicate that PDGFRA mutations in localised GIST may be twice as high as what was previously reported in patients with advanced disease. This finding may have important consequences for patients offered adjuvant imatinib, although most of these tumours are in the low-risk group. PMID- 20588274 TI - Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study. AB - BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA. PMID- 20588275 TI - Socioeconomic inequalities in cancer survival in England after the NHS cancer plan. AB - BACKGROUND: Socioeconomic inequalities in survival were observed for many cancers in England during 1981-1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan. MATERIALS AND METHOD: We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996-2006, followed up to 31 December 2007. Three periods were defined: 1996-2000 (before the Cancer Plan), 2001-2003 (initialisation) and 2004 2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods. RESULTS: Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1 year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis. CONCLUSION: The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups. PMID- 20588276 TI - The functional significance of microRNA-145 in prostate cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in numerous cellular processes. Recent studies have shown aberrant expression of miRNAs in prostate cancer tissues and cell lines. On the basis of miRNA microarray data, we found that miR-145 is significantly downregulated in prostate cancer. METHODS AND RESULTS: We investigated the expression and functional significance of miR-145 in prostate cancer. The expression of miR-145 was low in all the prostate cell lines tested (PC3, LNCaP and DU145) compared with the normal cell line, PWR-1E, and in cancerous regions of human prostate tissue when compared with the matched adjacent normal. Overexpression of miR-145 in PC3 transfected cells resulted in increased apoptosis and an increase in cells in the G2/M phase, as detected by flow cytometry. Investigation of the mechanisms of inactivation of miR-145 through epigenetic pathways revealed significant DNA methylation of the miR-145 promoter region in prostate cancer cell lines. Microarray analyses of miR-145-overexpressing PC3 cells showed upregulation of the pro-apoptotic gene TNFSF10, which was confirmed by real-time PCR and western analysis. CONCLUSION: One of the genes significantly upregulated by miR-145 overexpression is the proapoptotic gene TNFSF10. Therefore, modulation of miR-145 may be an important therapeutic approach for the management of prostate cancer. PMID- 20588277 TI - Nutlin-3, the small-molecule inhibitor of MDM2, promotes senescence and radiosensitises laryngeal carcinoma cells harbouring wild-type p53. AB - BACKGROUND: Primary radiotherapy (RT) is a mainstay of treatment for laryngeal squamous cell carcinoma (LSCC). Although the cure rates for early (T1) vocal cord tumours are high, RT proves ineffective in up to a third of T3 carcinomas. Moreover, RT is associated with debilitating early- and late-treatment-related toxicity, thus finding means to de-escalate therapy, while retaining/augmenting therapeutic effectiveness, is highly desirable. p53 is a key mediator of radiation responses; we therefore investigated whether Nutlin-3, a small-molecule inhibitor of MDM2 (mouse double minute 2; an essential negative regulator of p53), might radiosensitise LSCC cells. METHODS: We performed clonogenic assays to measure radiosensitivity in a panel of LSCC cell lines (for which we determined p53 mutational status) in the presence and absence of Nutlin-3. RESULTS: LSCC cells harbouring wild-type p53 were significantly radiosensitised by Nutlin-3 (P<0.0001; log-rank scale), and displayed increased cell cycle arrest and significantly increased senescence (P<0.001) in the absence of increased apoptosis; thus, our data suggest that senescence may mediate this increased radiosensitivity. CONCLUSION: This is the first study showing Nutlin-3 as an effective radiosensitiser in LSCC cells that retain wild-type p53. The clinical application of Nutlin-3 might improve local recurrence rates or allow treatment de-escalation in these patients. PMID- 20588278 TI - A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. AB - BACKGROUND: This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours. METHODS: Cohorts of three to six patients were treated with escalating doses of belinostat administered intravenously once daily, days 1-5 q21 days; on day 3, carboplatin (area under the curve (AUC) 5) and/or paclitaxel (175 mg m(-2)) were administered 2-3 h after the end of the belinostat infusion. RESULTS: In all 23 patients received 600-1000 mg m(-2) per day of belinostat with carboplatin and/or paclitaxel. No DLT was observed. The maximal administered dose of belinostat was 1000 mg m(-2) per day for days 1-5, with paclitaxel (175 mg m(-2)) and carboplatin AUC 5 administered on day 3. Grade III/IV adverse events were (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anaemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue (1; 4%), vomiting (1; 4%) and myalgia (1; 4%). The pharmacokinetics of belinostat, paclitaxel and carboplatin were unaltered by the concurrent administration. There were two partial responses (one rectal cancer and one pancreatic cancer). A third patient (mixed mullerian tumour of ovarian origin) showed a complete CA-125 response. In addition, six patients showed a stable disease lasting > or =6 months. CONCLUSION: The combination was well tolerated, with no evidence of pharmacokinetic interaction. Further evaluation of anti-tumour activity is warranted. PMID- 20588285 TI - A complementary approach to treating antibody-mediated transplant rejection. AB - Current treatment for antibody-mediated kidney transplant rejection is inadequate. Tillou and colleagues administered recombinant C1 inhibitor to block complement activation to prevent antibody-initiated injury in sensitized baboon recipients of kidney allografts. These early but encouraging results support further testing of the safety and efficacy of complement inhibition as part of a comprehensive strategy to treat this disease, both in animal models and ultimately in humans. PMID- 20588279 TI - Trastuzumab induced in vivo tissue remodelling associated in vitro with inhibition of the active forms of AKT and PTEN and RhoB induction in an ovarian carcinoma model. AB - BACKGROUND: The incidence of ovarian cancer has been increasing worldwide and it is currently the leading cause of death from gynaecological malignancy. Unlike breast cancer, the prognostic role of the human epidermal growth factor receptor 2 (HER-2) in ovarian carcinoma remains controversial. METHODS: The aim of this preclinical study was to further characterise the biological, molecular and cellular effects of trastuzumab (Herceptin) using NIH-OVCAR-3 and derived cell lines both in vitro and in vivo. RESULTS: In vitro assessments have shown that trastuzumab treatment inhibited total and phosphorylated HER-2. This was associated with inhibition of the phosphorylated form of phosphatase and tensin homologue (PTEN), mitogen-activated protein kinase and AKT, and the total level of p27(kip). Inhibition of PTEN is associated with phosphorylated MEK1/2 upregulation, suggesting a specific inhibition of the protein phosphatase function of PTEN. Moreover, trastuzumab induced the upregulation of RhoB. These molecular modifications promote inhibition of cell migration and potentially restoration of tumour cell contact inhibition. RhoB induction in NIH-OVCAR-3 control cell lines mimics the molecular and cellular trastuzumab long-time exposition effects. RhoB inhibition in NIH-OVCAR-3 long-time exposed to trastuzumab cell line reverses the cellular and molecular effects observed in this model. In vivo examinations have shown that these changes are also associated with the restoration of structural, morphological and normal functions of the peritoneum of an ovarian carcinoma mouse model. CONCLUSION: These results provide an indication of the mechanisms underlying the anti-tumour activity of trastuzumab that strongly implicate RhoB in an ovarian carcinoma model that does not show HER-2 amplification or overexpression. These findings highlight that trastuzumab effects involve a possible cross-talk between RhoB and PTEN in the early stages of tumour re-growth in a model of micrometastatic ovarian cancer. PMID- 20588286 TI - The nanopeptide hormone vasopressin is a new player in the modulation of renal Na(+)-Cl(-) cotransporter activity. AB - Vasopressin is a modulator of salt and water reabsorption, with known effects in the thick ascending limb and the collecting duct. Pedersen et al. present evidence that vasopressin administration increases the phosphorylation of the apical thiazide-sensitive Na(+)-Cl(-) cotransporter in the distal convoluted tubule. These effects appear to be independent of the renin-angiotensin system and to be mediated by the intracellular kinase SPAK. These observations expand the vasopressin-sensitive region of the nephron. PMID- 20588287 TI - Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism? AB - Genetic variation in MYH9, encoding non-muscle heavy chain IIA, has been recognized for over a decade as the cause of an autosomal dominant syndrome characterized by macrothrombocytopenia, neutrophil inclusions, and glomerular pathology. More recently, genetic variation in the MYH9 region on chromosome 22 has been associated with chronic kidney disease in African-descent individuals. A better understanding of the disease mechanisms responsible for glomerular injury in autosomal dominant MYH9 syndromes will lead to fuller appreciation of the role of this gene in glomerular biology. PMID- 20588288 TI - Rumpel-Leede phenomenon in a hemodialysis patient. PMID- 20588289 TI - Severe voiding dysfunction: ask the child to smile. PMID- 20588290 TI - Predictive power of the components of metabolic syndrome in its development: a 6.5-year follow-up in the Tehran Lipid and Glucose Study (TLGS). AB - BACKGROUND/OBJECTIVES: To determine which component of the metabolic syndrome (MetS) is the best predictor of its development. SUBJECTS/METHODS: In this cohort study, 2279 subjects aged 20-87 years without MetS selected from among the participants of the cross-sectional phase of the Tehran Lipid and Glucose Study (TLGS) were followed up for development of MetS. RESULTS: After a mean interval of 6.5 years, 462 and 602 new cases of MetS were diagnosed on the basis of the modified Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria, respectively. The adjusted odds ratio for development of MetS by ATP III criteria was highest for central obesity in men, 2.8 (2.2 3.7), and for triglycerides (TGs) in women, 2.8 (2.0-4.1). The adjusted odds ratio for the development of MetS by IDF criteria was highest for TGs in both men and women: odds ratio 2.8 (2.2-3.7) and 2.9 (1.9-4.3), respectively. A model that included waist circumference (WC) and TGs or WC and high-density lipoprotein (HDL) predicted MetS similar to a model that included all five MetS components. CONCLUSION: Screening for the timely prediction of the development of MetS should include measurement of WC, TGs and plasma HDL. PMID- 20588291 TI - Beneficial impact on cardiovascular risk profile of water buffalo meat consumption. AB - BACKGROUND/OBJECTIVES: Meat is a good source of proteins and irons, yet its consumption has been associated with unfavorable cardiovascular effects. Whether this applies to all types of meat is unclear. We thus aimed to appraise the impact of water buffalo meat consumption on cardiovascular risk profile with an observational longitudinal study. SUBJECTS/METHODS: Several important cardiovascular risk features were appraised at baseline and at 12-month follow-up in 300 adult subjects divided in groups: recent consumers of water buffalo meat vs subjects who had never consumed water buffalo meat. In addition, long-standing consumers of water buffalo meat were evaluated. RESULTS: Age, gender, height, body weight, and the remaining diet (with the exception of cow meat consumption) were similar across groups. From baseline to follow-up, recent consumers of water buffalo meat change their intake of water buffalo meat from none to 600+/-107 g per week (P<0.001), with ensuing reductions in cow meat consumption from 504+/ 104 to 4+/-28 (P<0.001). At the end of the study, recent consumers of water buffalo meat showed a significant decrease in total cholesterol and triglycerides levels, lower pulse wave velocity, as well as a more blunted response to oxidative stress from baseline to follow-up in comparison with subjects who had never consumed water buffalo meat (all P<0.05). CONCLUSIONS: Consumption of buffalo meat seems to be associated with several beneficial effects on cardiovascular risk profile. Awaiting further randomized clinical trials, this study suggests that a larger consumption of water buffalo meat could confer significant cardiovascular benefits, while continuing to provide a substantial proportion of the recommended daily allowance of protein. PMID- 20588292 TI - Initial weight loss on an 800-kcal diet as a predictor of weight loss success after 8 weeks: the Diogenes study. AB - OBJECTIVE: The purpose of this study was to investigate whether pre-treatment subject characteristics and weight change during the first weeks of a low-calorie diet (LCD) can predict weight loss outcomes at the end of a controlled 8-week weight loss period in overweight and obese adults. SUBJECTS: A total of 932 overweight and obese subjects of both genders were included at eight European centers, and underwent an 8-week LCD period. RESULTS: The weight loss at week 8 was positively correlated with initial body weight (Spearman's rho=0.62), height (rho=0.43), body mass index (rho=0.43), waist (rho=0.48) and hip circumference (rho=0.33), sagittal diameter (rho=0.45), fat mass (rho=0.35) and fat-free mass (rho=0.52), and gender (rho=-0.36) (all P<0.01). In the multivariate regression model, adjusted for center, only initial body weight, early weight loss (week 1) and weight loss at week 3 were significant predictors of weight loss outcome at week 8: weight loss (kg) at week 8=0.09+0.046 x baseline body weight (kg)-0.311 x weight loss (kg) at week 1+1.284 x weight loss (kg) at week 3 (R(2)=68%, P<0.0001). A weight loss of > or =2.6 kg at week 1 during the LCD period was identified as the optimal cut-off predictor for at least 10 kg weight loss at week 8. CONCLUSIONS: This study suggests that initial body weight, early weight loss (week 1) and weight loss at week 3 are predictors of final weight loss during an 8-week LCD, and may be used as early biomarkers of subsequent responses to an LCD diet. PMID- 20588293 TI - Dietary patterns associated with hypertension prevalence in the Cameroon defence forces. AB - BACKGROUND/OBJECTIVES: To assess the possible role of particular patterns of food consumption in the occurrence of hypertension. SUBJECTS/METHODS: A cross sectional study of 571 members of defence forces was carried out in eight military institutions in Yaounde, Cameroon. Blood pressure was measured with automatic sphygmomanometers simultaneously at both arms. Food consumption data were obtained through a food frequency questionnaire and lifestyle questionnaire was used to ascertain information on physical activity and other risk factors. RESULTS: Two dietary patterns were identified. The 'fruit and vegetable' pattern was typified by a high intake of fruits, vegetables, tubers and legumes. The 'meat' pattern was characterized by a high intake of bush meat, poultry and red meat. After adjustment for age, body mass index, rank, vigorous physical activity and total energy intake, the fruit and vegetable pattern was significantly associated with a reduced risk of hypertension (odds ratio (OR)=0.40; 95% confidence interval (CI)=0.20-0.83, P=0.04) when comparing the highest to the lowest quartile of dietary pattern scores. No significant relationship was apparent between the meat pattern and hypertension. CONCLUSIONS: Our findings suggest that a diet rich in fruits, vegetables, tubers and legumes may have an important role in regulating blood pressure. More prospective and extensive data are warranted to investigate the magnitude of cardiovascular disease in that specific population. PMID- 20588294 TI - Evaluation of leptin in breast milk, lactating mothers and their infants. AB - BACKGROUND/OBJECTIVES: Leptin is present in human milk, but it is not clear what the relationship between breast milk (BM) leptin levels and maternal and infant serum leptin concentrations is. The objective of this study was to evaluate the leptin concentration in BM and to investigate its relationship with infants' and mothers' anthropometric parameters and with serum leptin concentration in breast fed (BF) infants and lactating mothers. SUBJECTS/METHODS: We enrolled 36 adequate for gestational age healthy, exclusively BF, term infants aged <6 months. Leptin concentration in serum and BM was determined by radioimmunoassay (RIA) test (human-leptin-RIA-sensitive, Mediagnost). Infants' and mothers' weights, lengths and body mass indexes (BMI) were measured. RESULTS: The median leptin concentration was 3.42 ng/ml (interquartile range (IR): 2.65) in BF infants' serum, 3.02 ng/ml (IR: 2.85) in mothers' serum (n=17) and 0.51 ng/ml (IR: 0.34) in BM (n=24). BM leptin concentrations were significantly lower than serum BF infant (P<0.001) and maternal (P<0.001) leptin levels. Infant serum leptin concentration correlated positively with infant weight (r=0.437, P=0.008) and BMI (r=0.561, P=0.004). Mother serum leptin levels correlated positively with weight (r=0.755, P<0.001) and BMI (r=0.661, P=0.007). No correlations were found between BM leptin and serum leptin concentrations in BF infants and mothers. CONCLUSIONS: We confirmed the presence of leptin in BM at a lower concentration than that found in infant and lactating mother serum. We observed a positive correlation between serum leptin levels in BF infants and their growth parameters. PMID- 20588295 TI - RNA silencing: Nuclear RNAi in worms. PMID- 20588297 TI - Pyrenocine I, a new pyrenocine analog produced by Paecilomyces sp. FKI-3573. PMID- 20588296 TI - Membrane budding and scission by the ESCRT machinery: it's all in the neck. AB - The endosomal sorting complexes required for transport (ESCRTs) catalyse one of the most unusual membrane remodelling events in cell biology. ESCRT-I and ESCRT II direct membrane budding away from the cytosol by stabilizing bud necks without coating the buds and without being consumed in the buds. ESCRT-III cleaves the bud necks from their cytosolic faces. ESCRT-III-mediated membrane neck cleavage is crucial for many processes, including the biogenesis of multivesicular bodies, viral budding, cytokinesis and, probably, autophagy. Recent studies of ultrastructures induced by ESCRT-III overexpression in cells and the in vitro reconstitution of the budding and scission reactions have led to breakthroughs in understanding these remarkable membrane reactions. PMID- 20588298 TI - Rakicidin D, an inhibitor of tumor cell invasion from marine-derived Streptomyces sp. PMID- 20588299 TI - In vitro and in vivo anti-Trypanosoma brucei activities of phenazinomycin and related compounds. PMID- 20588300 TI - AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase. AB - The novel immunosuppressant AS1387392 has been isolated from Acremonium sp. No. 27082. This compound showed a strong inhibitory effect against mammalian histone deacetylase and T-cell proliferation. Further, AS1387392 showed a good oral absorption, and its plasma concentration was higher than that of FR235222, an analog of AS1387392 that inhibited histone deacetylase previously reported. Given these findings, AS1387392 may represent an important new lead in developing immunosuppressant. PMID- 20588301 TI - Molecular farming: production of drugs and vaccines in higher plants. AB - On the basis of developments in plant biotechnology, drug and vaccine production by higher plants can be added to microbial and animal cell culture processes. When genes encoding drug or vaccine formation under a suitable promoter are introduced into plants, these useful compounds can be economically produced from CO(2) and inorganic chemicals using sunlight. The merits and demerits of the plant process are discussed in this paper. PMID- 20588302 TI - Biosynthesis of rapamycin and its regulation: past achievements and recent progress. AB - Rapamycin and its analogs are clinically important macrolide compounds produced by Streptomyces hygroscopicus. They exhibit antifungal, immunosuppressive, antitumor, neuroprotective and antiaging activities. The core macrolactone ring of rapamycin is biosynthesized by hybrid type I modular polyketide synthase (PKS)/nonribosomal peptide synthetase systems primed with 4,5-dihydrocyclohex-1 ene-carboxylic acid. The linear polyketide chain is condensed with pipecolate by peptide synthetase, followed by cyclization to form the macrolide ring and modified by a series of post-PKS tailoring steps. The aim of this review was to outline past and recent advances in the biosynthesis and regulation of rapamycin, with an emphasis on the distinguished contributions of Professor Demain to the study of rapamycin. In addition, this article describes the biological activities as well as mechanism of action of rapamycin and its derivatives. Recent attempts to improve the productivity of rapamycin and generate diverse rapamycin analogs through mutasynthesis and mutagenesis are also introduced, along with some future perspectives. PMID- 20588303 TI - Surugapyrone A from Streptomyces coelicoflavus strain USF-6280 as a new DPPH radical-scavenger. AB - Surugapyrone A, a novel 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging 2 pyrone, was isolated from the culture filtrate of an actinomycete strain USF 6280. This strain was assigned to the genus Streptomyces owing to its morphological and chemotaxonomic characteristics. Phylogenetic analysis based on 16S ribosomal RNA gene sequences supported the classification of the producing strain as a member of the genus Streptomyces and indicated that it was closely related to Streptomyces coelicoflavus. As the morphological, physiological and biochemical characteristics of the producing strain were in agreement with those of the type strain of S. coelicoflavus, we concluded that strain USF-6280 should be identified as a member of S. coelicoflavus. The structure of surugapyrone A was determined to be 4-hydroxy-6-isopropyl-3-methyl-2-pyrone on the basis of the spectroscopic data. The results of feeding experiments with (13)C-labeled compounds indicated that surugapyrone A was biosynthesized through a polyketide pathway involving isobutyrate, acetate and propionate. PMID- 20588304 TI - Identification of the active component that induces vancomycin resistance in MRSA. AB - A fraction of methicillin-resistant Staphylococcus aureus (MRSA) shows resistance to vancomycin (VCM) in the presence of beta-lactam antibiotics (BIVR) at low concentrations. We hypothesized that the BIVR phenomenon might be exerted by a peptidoglycan derivative(s) generated as a consequence of beta-lactam antibiotic action. To verify this hypothesis, we isolated the fraction that mimicked the effect of beta-lactam antibiotics by the enzymatic treatment of the crude cell wall. The active components were purified by a combination of reverse phase chromatographies, mass spectrum and amino-acid analyses, and were identified to be a muropeptide with the following formula: N-acetyglucosamyl-N-acetylmuramyl- Ala-D-isoGln-L-Lys-(E-NH-4Gly)-D-Ala-2Gly. This is the very first identification of the active component, which induces VCM resistance in MRSA. We found that the BIVR cells are highly sensitive to this compound rendering the cells resistant to VCM compared with non-BIVR MRSA. PMID- 20588305 TI - Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. AB - Prader-Willi syndrome (PWS) is a neurobehavioral disorder manifested by infantile hypotonia and feeding difficulties in infancy, followed by morbid obesity secondary to hyperphagia. It is caused by deficiency of paternally expressed transcript(s) within the human chromosome region 15q11.2. PWS patients harboring balanced chromosomal translocations with breakpoints within small nuclear ribonucleoprotein polypeptide N (SNRPN) have provided indirect evidence for a role for the imprinted C/D box containing small nucleolar RNA (snoRNA) genes encoded downstream of SNRPN. In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology. In this study, we performed detailed phenotypic, cytogenetic, and molecular analyses including chromosome analysis, array comparative genomic hybridization (array CGH), expression studies, and single-nucleotide polymorphism (SNP) genotyping for parent-of-origin determination of the 15q11.2 microdeletion on an 11-year-old child expressing the major components of the PWS phenotype. This child had an ~236.29 kb microdeletion at 15q11.2 within the larger Prader Willi/Angelman syndrome critical region that included the SNORD116 cluster of snoRNAs. Analysis of SNP genotypes in proband and mother provided evidence in support of the deletion being on the paternal chromosome 15. This child also met most of the major PWS diagnostic criteria including infantile hypotonia, early onset morbid obesity, and hypogonadism. Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. Array CGH testing for genomic copy-number changes in cases with complex phenotypes is proving to be invaluable in detecting novel alterations and enabling better genotype-phenotype correlations. PMID- 20588306 TI - The medical geneticist as expert in the transgenerational and developmental aspects of diseases. AB - The increased knowledge of genetics has raised new questions, and confusion has been growing about the evaluation of the results of recent research and the role of geneticists in the genomic medicine. If we focus on transgenerational and developmental aspects of diseases, the answers might be more evident. PMID- 20588307 TI - Genome-wide scan identifies a quantitative trait locus at 4p15.3 for serum urate. AB - Elevated serum urate levels lead to gout and are associated with hypertension, metabolic syndrome, type 2 diabetes and cardiovascular diseases. The purpose of this study was to identify evidence for genetic linkage with serum urate and to determine whether variation within positional candidate genes is associated with serum urate levels in a non-European population. Genetic linkage analysis and single nucleotide polymorphism (SNP) genotyping was performed in a large family pedigree cohort from Mauritius. We assessed associations between serum urate levels and 97 SNPs in a positional candidate gene, SLC2A9. A genome-wide scan identified a new region with evidence for linkage for serum urate at 4p15.3. SNP genotyping identified significant association between six SNP variants in SLC2A9 and serum urate levels. Allelic and gender-based effects were noted for several SNPs. Significant correlations were also observed between serum urate levels and individual components of metabolic syndrome. Our study results implicate genetic variation in SLC2A9 in influencing levels of serum urate over a broad range of values in a large Mauritian family cohort. PMID- 20588309 TI - Name of the game. PMID- 20588310 TI - Motivated research. PMID- 20588308 TI - Dengue hemorrhagic fever is associated with polymorphisms in JAK1. AB - To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever (DHF), 236 dengue fever (DF), and 236 asymptomatic infections were genotyped for 593 single-nucleotide polymorphisms (SNPs) in 56 genes across the type 1 interferon (IFN) response pathway as well as other important candidate genes. By single locus analysis comparing DHF with DF, 11 of the 51 markers with P<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when P<6 * 10(-4)). The JAK1 SNPs showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC SIGN). An association between DHF and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 IFN-stimulated gene expression in these patients. PMID- 20588311 TI - The evo-devo comet. PMID- 20588312 TI - Crop shortages. A lack of breeders to apply the knowledge from plant science is jeopardizing public breeding programmes and the training of future plant scientists. PMID- 20588313 TI - Massing life. Research into biomass and food chains attracts increasing attention, given the biosphere's capacity to sequester CO2 from the atmosphere. PMID- 20588314 TI - Prediction of infarct volume and neurologic outcome by using automated multiparametric perfusion-weighted magnetic resonance imaging in a primate model of permanent middle cerebral artery occlusion. AB - By optimizing thresholds, we identified the perfusion-weighted magnetic resonance imaging (PWI) parameters that accurately predict final infarct volume and neurologic outcome in a primate model of permanent middle cerebral artery (MCA) occlusion. Ten cynomolgus monkeys underwent PWI and diffusion-weighted imaging (DWI) at 3 and 47 hours, respectively, after right MCA occlusion using platinum coils, and were killed at 48 hours. Volumes of the hypoperfused areas on PWI were automatically measured using different thresholds and 11 parametric maps to determine the optimum threshold (at which least difference was found between the average volumes on PWI and those determined using specimens or DWI). In the case of arrival time (AT), cerebral blood volume (CBV), time to peak (TTP), time to maximum (T(max)), and cerebral blood flow (CBF) determined using deconvolution techniques, the volume of the hypoperfused area significantly correlated with the infarct volumes and the neurologic deficit scores with small variations, whereas in the case of mean transit time and nondeconvolution CBF, relatively poor correlations with large variations were seen. At optimum threshold, AT, CBV, TTP, T(max), and deconvolution CBF can accurately predict the final infarct volume and neurologic outcome in monkeys with permanent MCA occlusion. PMID- 20588315 TI - Temporary [corrected] cerebral ischemia results in swollen astrocytic end-feet that compress microvessels and lead to delayed [corrected] focal cortical infarction. AB - We examined the mechanisms underlying the abrupt onset of the focal infarction in disseminated selective neuronal necrosis (DSNN) after temporary ischemia. Stroke positive animals were selected according to their stroke-index score during the first 10 minutes after left carotid occlusion performed twice at a 5-hour interval. The animals were euthanized at various times after the second ischemia. Light- and electron-microscopical studies were performed chronologically on the coronal-cut surface of the cerebral cortex at the chiasmatic level, where focal infarction evolved in the maturing DSNN. We counted the number of neurons, astrocytes, and astrocytic processes (APs); measured the areas of end-feet and astrocytes; and counted the numbers of obstructed microvessels and carbon-black suspension-perfused microvessels (CBSPm). Between 0.5 and 5 hours after ischemia, DSNN matured, with the numbers of degenerated and dead neurons increasing, and those of APs cut-ends decreasing; whereas the area of the end-feet and the numbers of obstructed microvessels increased and those of CBSPm decreased. At 12 and 24 hours after ischemia, the infarction evolved, with the area of end-feet and astrocytic number decreased; whereas the numbers of obstructed microvessels decreased and the CBSPm number increased. The focal infarction evolved by temporary microvascular obstruction because of compression by swollen end-feet. PMID- 20588316 TI - Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice. AB - The apolipoprotein E4 (APOE4) gene leads to increased brain amyloid beta (Abeta) and poor outcome in adults with traumatic brain injury (TBI); however, its role in childhood TBI is controversial. We hypothesized that the transgenic expression of human APOE4 worsens the outcome after controlled cortical impact (CCI) in adult but not immature mice. Adult and immature APOE4 mice had worse motor outcome after CCI (P<0.001 versus wild type (WT)), but the Morris water maze performance was worse only in adult APOE4 mice (P=0.028 at 2 weeks, P=0.019 at 6 months versus WT), because immature APOE4 mice had performance similar to WT for up to 1 year after injury. Brain lesion size was similar in adult APOE4 mice but was decreased (P=0.029 versus WT) in injured immature APOE4 mice. Microgliosis was similar in all groups. Soluble brain Abeta(40) was increased at 48 hours after CCI in adult and immature APOE4 mice and in adult WT (P<0.05), and was dynamically regulated during the chronic period by APOE4 in adults but not immature mice. The data suggest age-dependent effects of APOE4 on cognitive outcome after TBI, and that therapies targeting APOE4 may be more effective in adults versus children with TBI. PMID- 20588317 TI - PET scan perfusion imaging in the Prader-Willi syndrome: new insights into the psychiatric and social disturbances. AB - The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals. PMID- 20588318 TI - Cerebral dynamics and metabolism of hyperpolarized [1-(13)C]pyruvate using time resolved MR spectroscopic imaging. AB - Dynamic hyperpolarized [1-(13)C]pyruvate metabolic imaging in the normal anesthetized rat brain is demonstrated on a clinical 3-T magnetic resonance imaging scanner. A 12-second bolus injection of hyperpolarized [1-(13)C]pyruvate is imaged at a 3-second temporal resolution. The observed dynamics are evaluated with regard to cerebral blood volume (CBV), flow, transport, and metabolic exchange with the cerebral lactate pool. A model for brain [1-(13)C]lactate, based on blood-brain transport kinetics, CBV, and the observed pyruvate dynamics is described. PMID- 20588319 TI - Role of salt-induced kinase 1 in androgen neuroprotection against cerebral ischemia. AB - Androgens within physiological ranges protect castrated male mice from cerebral ischemic injury. Yet, underlying mechanisms are unclear. Here, we report that, after middle cerebral artery occlusion (MCAO), salt-induced kinase 1 (SIK1) was induced by a potent androgen-dihydrotestosterone (DHT) at protective doses. To investigate whether SIK1 contributes to DHT neuroprotection after cerebral ischemia, we constructed lentivirus-expressing small interference RNA (siRNA) against SIK1. The SIK1 knockdown by siRNA exacerbated oxygen-glucose deprivation (OGD)-induced cell death in primary cortical neurons, suggesting that SIK1 is an endogenous neuroprotective gene against cerebral ischemia. Furthermore, lentivirus-mediated SIK1 knockdown increased both cortical and striatal infarct sizes in castrated mice treated with a protective dose of DHT. Earlier studies show that SIK1 inhibits histone deacetylase (HDAC) activities by acting as a class IIa HDAC kinase. We observed that SIK1 knockdown decreased histone H3 acetylation in primary neurons. The SIK1 siRNA also exacerbated OGD-induced neuronal death in the presence of trichostatin A (TSA), an HDAC inhibitor, and decreased histone H3 acetylation at 4 hours reoxygenation in TSA-treated neurons. Finally, we showed that DHT at protective doses prevented ischemia-induced histone deacetylation after MCAO. Our finding suggests that SIK1 contributes to neuroprotection by androgens within physiological ranges by inhibiting histone deacetylation. PMID- 20588320 TI - Gabapentin suppresses cortical spreading depression susceptibility. AB - Cortical spreading depression (CSD) is an intense depolarization wave implicated in the pathophysiology of brain injury states and migraine aura. As Ca(v)2.1 channels modulate CSD susceptibility, we tested gabapentin, which inhibits Ca(v)2.1 through high-affinity binding to its alpha(2)delta subunit, on CSD susceptibility in anesthetized rats. Gabapentin, 100 or 200 mg/kg, elevated the electrical threshold for CSD and diminished recurrent CSDs evoked by topical KCl, when administered 1 hour before testing. With its favorable safety and tolerability profile, gabapentin may have a role in suppression of injury depolarizations in stroke, intracranial hemorrhage, and traumatic brain injury. PMID- 20588321 TI - Intraoperative blood flow analysis of direct revascularization procedures in patients with moyamoya disease. AB - Moyamoya disease is characterized by the progressive stenosis and often occlusion of the terminal internal carotid arteries, which leads to ischemic and hemorrhagic injuries. The etiology is unknown and surgical revascularization remains the mainstay treatment. We analyzed various hemodynamic factors in 292 patients with moyamoya disease, representing 496 revascularization procedures, including vessel dimension and intraoperative blood flow, using a perivascular ultrasonic flowprobe. Mean middle cerebral artery (MCA) flow rate was 4.4 +/- 0.26 mL/min. After superficial temporal artery (STA)-MCA bypass surgery, flows at the microanastomosis were increased fivefold to a mean of 22.2 +/- 0.8 mL/min. The MCA flows were significantly lower in the pediatric (16.2 +/- 1.3 mL/min) compared with the adult (23.9 +/- 1.0 mL/min; P<0.0001) population. Increased local flow rates were associated with clinical improvement. Permanent postoperative complications were low (<5%), but very high postanastomosis MCA flow was associated with postoperative stroke (31.2 +/- 6.8 mL/min; P=0.045), hemorrhage (32.1 +/- 10.2 mL/min; P=0.045), and transient neurologic deficits (28.6 +/- 5.6 mL/min; P=0.047) compared with controls. Other flow and vessel dimension data are presented to elucidate the hemodynamic changes related to the vasculopathy and subsequent to surgical intervention. PMID- 20588322 TI - Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice. AB - We hypothesized that activation of the central histaminergic system is required for neuroprotection induced by hypoxic preconditioning. Wild-type (WT) and histidine decarboxylase knockout (HDC-KO) mice were preconditioned by 3 hours of hypoxia (8% O(2)) and, 48 hours later, subjected to 30 minutes of middle cerebral artery (MCA) occlusion, followed by 24 hours of reperfusion. Hypoxic preconditioning improved neurologic function and decreased infarct volume in WT or HDC-KO mice treated with histamine, but not in HDC-KO or WT mice treated with alpha-fluoromethylhistidine (alpha-FMH, an inhibitor of HDC). Laser-Doppler flowmetry analysis showed that hypoxic preconditioning ameliorated cerebral blood flow (CBF) in the periphery of the MCA territory during ischemia in WT mice but not in HDC-KO mice. Histamine decreased in the cortex of WT mice after 2, 3, and 4 hours of hypoxia, and HDC activity increased after 3 hours of hypoxia. Vascular endothelial growth factor (VEGF) mRNA and protein expressions showed a greater increase after hypoxia than those in HDC-KO or alpha-FMH-treated WT mice. In addition, the VEGF receptor-2 antagonist SU1498 prevented the protective effect of hypoxic preconditioning in infarct volume and reversed increased peripheral CBF in WT mice. Therefore, endogenous histamine is an essential mediator of hypoxic preconditioning. It may function by enhancing hypoxia-induced VEGF expression. PMID- 20588323 TI - Residential insecticide usage in northern California homes with young children. AB - Residential insecticide usage and actual application details were collected in a population-based sample of 477 households residing within 22 counties in northern California with at least one child of age <= 5 years between January 2006 and August 2008. Structured telephone interviews were conducted collecting information on residential use of insecticides, including outdoor sprays, indoor sprays, indoor foggers, applications by professionals, and pet flea/tick control during the previous year. Interviews also covered post-treatment behaviors, which influence post-application exposure levels. Altogether, 80% of the households applied some type of insecticide in the previous year, with half of this population using two or more application methods. Of the households using insecticides, half reported applying insecticides relatively infrequently (<4 times per year), whereas 11-13% reported high frequency of use (>24 times per year). Application frequency was temperature dependent, with significantly more applications during the warmer months from May through October. Spot treatments appeared to be the most prevalent application pattern for sprays. For one out of three of the indoor applications, children played in the treated rooms on the day of the application, and for 40% of the outdoor applications, pets played in the treated area on the day of the application. These findings describing the intensity of insecticide use and accompanying behaviors in families with young children may inform future insecticide exposure modeling efforts, and ultimately, risk assessments. PMID- 20588324 TI - Characterization of the elemental composition of newborn blood spots using sector field inductively coupled plasma-mass spectrometry. AB - We developed extraction and analysis protocols for element detection in neonatal blood spots (NBSs) using sector-field inductively coupled plasma-mass spectrometry (SF-ICP-MS). A 5% (v/v) nitric acid element extraction protocol was optimized and used to simultaneously measure 28 elements in NBS card filter paper and 150 NBSs. NBS element concentrations were corrected for filter paper background contributions estimated from measurements in samples obtained from either unspotted or spotted NBS cards. A lower 95% uncertainty limit (UL) that accounted for ICP-MS method, filter paper element concentration, and element recovery uncertainties was calculated by standard methods for each individual's NBS element concentration. Filter paper median element levels were highly variable within and between lots for most elements. After accounting for measurement uncertainties, 11 elements (Ca, Cs, Cu, Fe, K, Mg, Na, P, Rb, S, and Zn) had lower 95% ULs>0 ng/spot with estimated concentrations ranging from 0.05 to >50,000 ng/spot in >=50% of NBS samples in both correction methods. In a NBS sample minority, Li, Cd, Cs, Cr, Ni, Mo, and Pb had estimated concentrations >=20 fold higher than the respective median level. Taking measurement uncertainties into account, this assay could be used for semiquantitative newborn blood element measurement and for the detection of individuals exposed to supraphysiologic levels of some trace elements. Adequate control of filter paper element contributions remains the primary obstacle to fully quantitative element measurement in newborn blood using NBSs. PMID- 20588326 TI - Stable continuous-wave single-frequency Nd:YAG blue laser at 473 nm considering the influence of the energy-transfer upconversion. AB - We report a continuous-wave (cw) single frequency Nd:YAG blue laser at 473 nm end pumped by a laser diode. A ring laser resonator was designed, the frequency doubling efficiency and the length of nonlinear crystal were optimized based on the investigation of the influence of the frequency doubling efficiency on the thermal lensing effect induced by energy-transfer upconversion. By intracavity frequency doubling with PPKTP crystal, an output power of 1 W all-solid-state cw blue laser of single-frequency operation was achieved. The stability of the blue output power was better than +/- 1.8% in the given four hours. PMID- 20588325 TI - The impact of daily mobility on exposure to traffic-related air pollution and health effect estimates. AB - Epidemiological studies of traffic-related air pollution typically estimate exposures at residential locations only; however, if study subjects spend time away from home, exposure measurement error, and therefore bias, may be introduced into epidemiological analyses. For two study areas (Vancouver, British Columbia, and Southern California), we use paired residence- and mobility-based estimates of individual exposure to ambient nitrogen dioxide, and apply error theory to calculate bias for scenarios when mobility is not considered. In Vancouver, the mean bias was 0.84 (range: 0.79-0.89; SD: 0.01), indicating potential bias of an effect estimate toward the null by ~16% when using residence-based exposure estimates. Bias was more strongly negative (mean: 0.70, range: 0.63-0.77, SD: 0.02) when the underlying pollution estimates had higher spatial variation (land use regression versus monitor interpolation). In Southern California, bias was seen to become more strongly negative with increasing time and distance spent away from home (e.g., 0.99 for 0-2 h spent at least 10 km away, 0.66 for >= 10 h spent at least 40 km away). Our results suggest that ignoring daily mobility patterns can contribute to bias toward the null hypothesis in epidemiological studies using individual-level exposure estimates. PMID- 20588327 TI - Diode-end-pumped passively Q-switched 1.33 microm Nd:Gd3AlxGa(5-x)O12 laser with V3+: YAG saturable absorber. AB - We demonstrated the 1.33 microm laser performance with Nd:Gd(3)Al(x)Ga(5-x)O(12) (x = 0.94) (Nd:GAGG) laser crystals for the first time. Continuous-wave (cw) output power of 2.45 W was obtained with the optical-optical conversion efficiency of 21.8% and slope efficiency of 23.3%. In the passive Q-switching regime, the highest output power, the shortest pulse width, largest pulse energy and highest peak power were achieved to be 326 mW 18.2 ns, 36.3 microJ and 2.0 kW, respectively, with V(3+):YAG crystal as the saturable absorber. PMID- 20588328 TI - Sidelobe suppression in all-fiber acousto-optic tunable filter using torsional acoustic wave. AB - We propose two techniques to suppress intrinsic sidelobe spectra in all-fiber acousto-optic tunable filter using torsional acoustic wave. The techniques are based on either double-pass filter configuration or axial tailoring of mode coupling strength along an acousto-optic interaction region in a highly birefringent optical fiber. The sidelobe peak in the filter spectrum is experimentally suppressed from -8.3 dB to -16.4 dB by employing double-pass configuration. Axial modulation of acousto-optic coupling strength is proposed using axial variation of the fiber diameter, and the simulation results show that the maximum side peak of -9.3 dB can be reduced to -22.2dB. We also discuss the possibility of further spectral shaping of the filter based on the axial tailoring of acousto-optic coupling strength. PMID- 20588330 TI - Measurements of polarimetric sensitivity to hydrostatic pressure, strain and temperature in birefringent dual-core microstructured polymer fiber. AB - We experimentally characterized a birefringent microstructured polymer fiber of specific construction, which allows for single mode propagation in two cores separated by a pair of large holes. The fiber exhibits high birefringence in each of the cores as well as relatively weak coupling between the cores. Spectral dependence of the group and the phase modal birefringence was measured using an interferometric method. We have also measured the sensing characteristics of the fiber such as polarimetric sensitivity to hydrostatic pressure, strain and temperature. Moreover, we have studied the effect of hydrostatic pressure and strain on coupling between the cores. PMID- 20588329 TI - 3D in vivo optical coherence tomography based on a low-voltage, large-scan-range 2D MEMS mirror. AB - 3D in vivo optical imaging on a mouse has been obtained using a 2D MEMS mirror for lateral scanning in a time-domain optical coherence tomography (OCT) system. The MEMS mirror aperture size is 1 x 1 mm(2), and the device footprint is 2 x 2 mm(2). The MEMS mirror scans +/- 30 degrees optical angles about both x and y axis at only 5.5V DC voltage. An endoscopic probe with an outer diameter of 5.8 mm has been designed, manufactured and packaged. The probe scans an average transverse area of 2 mm x 2 mm. The imaging speed of the probe is about 2.5 frames per second, limited by the speed of the employed optical delay line. PMID- 20588331 TI - Bit-error rate performance of coherent optical M-ary PSK/QAM using decision-aided maximum likelihood phase estimation. AB - The bit-error rate (BER) expressions of 16- phase-shift keying (PSK) and 16- quadrature amplitude modulation (QAM) are analytically obtained in the presence of a phase error. By averaging over the statistics of the phase error, the performance penalty can be analytically examined as a function of the phase error variance. The phase error variances leading to a 1-dB signal-to-noise ratio per bit penalty at BER=10(-4) have been found to be 8.7 x 10(-2) rad(2), 1.2 x 10(-2) rad(2), 2.4 x 10(-3) rad(2), 6.0 x 10(-4) rad(2) and 2.3 x 10(-3) rad(2) for binary, quadrature, 8-, and 16-PSK and 16QAM, respectively. With the knowledge of the allowable phase error variance, the corresponding laser linewidth tolerance can be predicted. We extend the phase error variance analysis of decision-aided maximum likelihood carrier phase estimation in M-ary PSK to 16QAM, and successfully predict the laser linewidth tolerance in different modulation formats, which agrees well with the Monte Carlo simulations. Finally, approximate BER expressions for different modulation formats are introduced to allow a quick estimation of the BER performance as a function of the phase error variance. Further, the BER approximations give a lower bound on the laser linewidth requirements in M-ary PSK and 16QAM. It is shown that as far as laser linewidth tolerance is concerned, 16QAM outperforms 16PSK which has the same spectral efficiency (SE), and has nearly the same performance as 8PSK which has lower SE. Thus, 16-QAM is a promising modulation format for high SE coherent optical communications. PMID- 20588332 TI - Study on the time-varying and propagating characteristics of ultrashort pulse Laguerre-Gaussian beams. AB - This work proposes a simple model of pulse Laguerre-Gaussian Beams (LGBs) by chopping the incident continuous wave LGB into ultrashort pulse. The pulse LGBs are expanded into a series of LGBs with the same angular quantum number (AQN), whose expansion coefficients show the time-varying and propagating characteristics. Bigger radial quantum number (RQN) of incident LGB will cause more serious mode dispersion. This work discusses the case of zero RQN incident LGB intensively, in which the original modes, i.e. the same eigen-modes as the incident beams, can be used to approximate the pulse LGBs in short propagating range, e.g. 2zR. The original modes decrease, expand and delay when propagating, and it's more evident for incident LGBs with larger AQN . These conclusions are important for the optical communication by using the OAM division multiplexing (OAM-DM) technology. PMID- 20588333 TI - Theoretical and experimental study on the Nd:YAG/BaWO4/KTP yellow laser generating 8.3 W output power. AB - A diode-side-pumped actively Q-switched intracavity frequency-doubled Nd:YAG/BaWO(4)/KTP Raman laser is studied experimentally and theoretically. Rate equations are used to analyze the Q-switched yellow laser by considering the transversal distributions of the intracavity photon density and the inversion population density. An 8.3 W 590 nm laser is obtained with a 125.8 W 808 nm pump power and a 15 kHz pulse repetition frequency. The corresponding optical conversion efficiency from diode laser to yellow laser is 6.57%, much higher than that of the former reported side-pumped yellow laser. The output powers with respect to the incident pump power are in agreement with the theoretical results on the whole. PMID- 20588334 TI - Anomalous reflection from hybrid metamaterial slab. AB - We report for the first time that an ultra-thin hybrid metamaterial slab can reflect an incident plane wave in -1st diffraction order, giving rise to anomalous reflection in a "negative" way. The functionality is derived from the hybridized surface resonant states of the slab. The retro-directive reflection is demonstrated numerically for a Gaussian beam at oblique incidence and verified experimentally at microwave frequencies. PMID- 20588335 TI - Silicon-on-sapphire integrated waveguides for the mid-infrared. AB - Silicon waveguides are now widely used to guide radiation in the near-infrared, mainly in the wavelength range of 1.1 - 2.2 microm. While low-loss waveguides at longer wavelengths in silicon have been proposed, experimental realization has been elusive. Here we show that single-mode integrated silicon-on-sapphire waveguides can be used at mid-infrared wavelengths. We demonstrate waveguiding at 4.5 microm, or 2222.2 cm(-1), with losses of 4.3 +/- 0.6 dB/cm. This result represents the first practical integrated waveguide system for the mid-infrared in silicon, and enables a range of new applications. PMID- 20588336 TI - Fabrication of three-dimensional 1 x 4 splitter waveguides inside a glass substrate with spatially phase modulated laser beam. AB - Multiple light spots can be generated by modulating the spatial phase distribution of laser beam with a spatial light modulator (SLM). In this paper, we demonstrate the fabrication of three-dimensional 1 x 4 splitter waveguides inside a glass by focusing multiple light spots of femtosecond (fs) laser pulses, which can be controlled by switching spatial phase distributions on an SLM. In the conventional fs laser writing technique, a highly precise positioning of a substrate is essential for fabricating a branched waveguide in a splitter. Using the technique proposed in this paper, a continuously branched waveguide can be produced easily by translating a glass substrate only one time; therefore this technique can eliminate the need for a high precision in positioning of a substrate and save a fabrication time. PMID- 20588337 TI - Enhanced emission from BaMgAl10O17:Eu2+ by localized surface plasmon resonance of silver particles. AB - The visible emission of BaMgAl(10)O(17):Eu(2+) used for White LED and ACPDPs was enhanced by coupling electric transition with the localized surface plasmon oscillation of nanoscaled Ag particles. Phosphor films including Ag particles were prepared by the spin-coating method. Up to a 36% enhancement of the peak intensity, which was dependent on the morphology and concentration of Ag particles, was obtained. It was verified that the spectral overlap between the LSP energy of metal particle and the emission spectra of phosphor materials decided between the enhancement and quenching of the emission. It was indicated that localized field enhancement due to the LSPR of metal nanoparticles could improve the emission intensity of phosphor doped rare earth ions. PMID- 20588338 TI - Random lasing in ballistic and diffusiveregimes for macroporous silica-based systems with tunable scattering strength. AB - We have systematically investigated random lasing properties in weakly scattering systems composed of a macroporous silica disk immersed in a dye solution where the solvent is a mixture of two alcohols. Controlling the refractive index of the mixed solvent allows us to vary the scattering strength over a wide range. We have found two different scattering regimes where sharp spectral spikes with linewidth less than 1.0 nm, i.e., random laser with coherent feedback, appear in emission spectra. When the refractive index contrast between the solvent and the silica is very small, random lasing with coherent feedback is observed although the system appears nearly transparent. The coherent feedback vanishes when the refractive index contrast is increased up to a critical value, while further increase in the refractive index contrast results in the revival of the coherent feedback. We suggest that the existence of underlying microcavities plays an important role in the very weakly scattering regime (ballistic) while other mechanisms such as amplified extended modes may lead to the coherent feedback in lasing oscillation when the scattering strength increases. PMID- 20588339 TI - High efficient single-frequency output at 1991 nm from a diode-pumped Tm:YAP coupled cavity. AB - A coupled resonator was developed for high efficient room-temperature single frequency laser operating near 2 mum optical spectral region. 721 mW stable single-longitudinal-mode oscillation at 1991 nm was obtained when the absorbed pumping power was 2.4 W. The optical-to-optical efficiency was 30%, and the slope efficiency was 46%. 5 nm of frequency tuning range was obtained with stable output power. The beam propagation factors M2 were 1.43 and 1.42 in x and y directions, respectively. PMID- 20588340 TI - Imprinted terahertz artificial dielectric quarter wave plates. AB - We have developed low-loss polymer artificial dielectric quarter wave plates (QWP) operating at 2.6, 3.2 and 3.8 THz. The QWPs are imprinted on high density polyethylene (HDPE) using silicon masters. The grating period for the quarter wave plates is 60 microm. 330 microm, 280 microm and 230 microm deep gratings are used to obtain a pi/2 phase retardance between TE and TM polarization propagating through the QWPs. High frequency structure simulator (HFSS) was used to optimize the grating depth. Since the required grating depth is high, two plates, fixed in a back-to-back configuration were used for each QWP. A maximum aspect ratio (grating height/grating width) of 6.6 was used. PMID- 20588341 TI - Tunable-wavelength second harmonic generation from GaP photonic crystal cavities coupled to fiber tapers. AB - We demonstrate up to 30 nm tuning of gallium phosphide photonic crystal cavities resonances at aproximately 1.5 microm using a tapered optical fiber. The tuning is achieved through a combination of near-field perturbations and mechanical deformation of the membrane, both induced by the fiber probe. By exploiting this effect, we show fiber-coupled second harmonic generation with a tuning range of nearly 10 nm at the second harmonic wavelength of approximately 750 nm. By scaling cavity parameters, the signal could easily be shifted into other parts of the visible spectrum. PMID- 20588342 TI - Surface plasmon-coupled emission from shaped PMMA films doped with fluorescence molecules. AB - Surface plasmon-coupled emission from shaped PMMA films doped with randomly oriented fluorescence molecules was investigated. Experimental results show that for different shapes, such as triangle or circular structures, the SPCE ring displays different intensity patterns. For a given shape, it was observed that the relative position and polarization of an incident laser spot on the shaped PMMA can be used to adjust the fluorescence intensity distribution of the SPCE ring. The proposed method enables controlling the fluorescence emission in azimuthal direction in addition to the radial angle controlled by common SPCE, which will further enhances the fluorescence collection efficiency and has applications in fluorescence sensing, imaging and so on. PMID- 20588343 TI - Compact all-fiber optical Faraday components using 65-wt%-terbium-doped fiber with a record Verdet constant of -32 rad/(Tm). AB - A compact all-fiber Faraday isolator and a Faraday mirror are demonstrated. At the core of each of these components is an all-fiber Faraday rotator made of a 4 cm-long, 65-wt%-terbium-doped silicate fiber. The effective Verdet constant of the terbium-doped fiber is measured to be -32 rad/(Tm), which is 27 x larger than that of silica fiber. This effective Verdet constant is the largest value measured to date in any fiber and is 83% of the Verdet constant of commercially available crystal used in bulk optics-based isolators. Combining the all-fiber Faraday rotator with fiber polarizers results in a fully fusion spliced all-fiber isolator whose isolation is measured to be 19 dB. Combining the all-fiber Faraday rotator with a fiber Bragg grating results in an all-fiber Faraday mirror that rotates the polarization state of the reflected light by 88 +/- 4 degrees . PMID- 20588344 TI - Improved bending property of half-filled photonic crystal fiber. AB - A half-filling technique was demonstrated to improve the bending properties of a fluid-filled photonic crystal fiber. Such a technique can realize to fill selectively a fluid into half of air holes in a PCF. The bending properties of the half-filled PCF are quite different from those of the fully-filled PCF. Distinct bending properties were observed when the half-filled PCF was bent toward different fiber orientations. Especially, the transmission spectrum of the half-filled PCF was hardly affected while the fiber was bent toward the filled hole orientation. PMID- 20588345 TI - Multi-wavelength study of light transmitted through a single marine centric diatom. AB - The characterization of partially coherent light transmission by micrometer sized valves of marine diatoms is an interesting optical challenge and, from the biological point of view, is of outmost relevance in order to understand evolution mechanisms of such organisms. In the present work, we have studied the transmission of light coming from a monochromator through single valves of Coscinodiscus wailesii diatoms. Incoming light is confined by the regular pore pattern of the diatom surface into a spot of few microns, its dimensions depending on wavelength. The effect is ascribed to the superposition of wavefronts diffracted by the pores' edges. Numerical simulations help to demonstrate how this effect is not present in the ultraviolet region of the light spectrum, showing one of the possible evolutionary advantages represented by the regular pores patterns of the valves. PMID- 20588346 TI - Negative index modes in surface plasmon waveguides: a study of the relations between lossless and lossy cases. AB - Surface plasmon modes in structures of metal-insulator-metal (MIM), insulator insulator-metal (IIM) and insulator-metal-insulator (IMI) are studied theoretically for both lossless and lossy cases. Causality dictates which solutions of Maxwell's equations we accept for these structures. We find that for both lossless and lossy cases, the negative index modes and positive index modes are independent and should be treated separately. For the lossless case, our results differ from some published papers. By studying in detail the lossy case, we demonstrate how the curves should look like. PMID- 20588347 TI - Performance of short-range non-line-of-sight LED-based ultraviolet communication receivers. AB - Utilizing an empirical path loss model proposed in the first paper of a two-part series, the bit error rate performance of short-range non-line-of-sight ultraviolet communication receivers is analyzed. Typical photodetector models and modulation formats are considered. Our results provide semi-analytical prediction of the achievable communication performance as a function of system and channel parameters, and serve as a basis for system design. PMID- 20588348 TI - An optically-interrogated microwave-Poynting-vector sensor using cadmium manganese telluride. AB - A single <110> cadmium-manganese-telluride crystal that exhibits both the Pockels and Faraday effects is used to produce a Poynting-vector sensor for signals in the microwave regime. This multi-birefringent crystal can independently measure either electric or magnetic fields through control of the polarization of the optical probe beam. After obtaining all the relevant electric and magnetic field components, a map of the Poynting vector along a 50-Omega microstrip was experimentally determined without the need for any further transformational calculations. The results demonstrate that this sensor can be used for near-field mapping of the Poynting vector. Utilizing both amplitude and phase information from the fields in the microwave signal, it was confirmed for the case of an open terminated microstrip that no energy flowed to the load, while for a microstrip with a matched termination, the energy flowed consistently along the transmission line. PMID- 20588349 TI - Antireflection coatings for multilayer-type photonic crystals. AB - The possibility of antireflection (AR) coatings on a dielectric multilayer having sub-wavelength deep structural modification is investigated. We numerically surveyed the effect of reflectivity reduction attained by double-layer AR coatings for a wavy multilayer on a patterned substrate. It was clarified that double-layer AR coatings for wavy multilayer is possible with a similar performance level as conventional flat multilayer. Also, it was demonstrated that a pair of AR layers effectively works for a wide range of the horizontal pitch. PMID- 20588350 TI - Degradation of cloaking by two closely neighboring cloaks. AB - Cloaking can prevent a scattering object from detection by electromagnetic waves as it can significantly reduce the scattering cross section of the object. In this work we show that when two cloaks are placed in close neighborhood, the interaction will greatly enhance the perturbation of near field and significantly increase the scattering cross section compared with a single cloak. This means that the cloaking functionality may strongly degrade when two or more cloaks come close to each other. This offers a route to break down electromagnetic cloaking. PMID- 20588351 TI - Elimination of phase singularity to achieve superresolution in lossy metamaterials. AB - The presence of absorption losses softens the singular behavior of transmission resonances and leads to a good image in spite of limited effective spatial frequency range. Nonetheless, we found that the phase singularity does not disappear despite the considerably reduced retardation effects by softening the transmission resonances. Because the phase singularity severely deteriorates the ideal image reconstruction, broad transmission bandwidth in spatial frequency domain is not sufficient enough to achieve superresolution in TiO(2) thin film lens. The present work predicts successful elimination of the phase singularity and the achievement of approximately lambda /12.9 superresolution in TiO(2) thin film lens through the phase correction method. PMID- 20588352 TI - Adaptive multi/demultiplexers for optical signals with arbitrary wavelength spacing. AB - We propose and demonstrate the principle of a novel adaptive wavelength division multiplexer/demultiplexer structure based on Opto-VLSI processing. By driving an Opto-VLSI processor with an appropriate phase hologram, optical signals of arbitrary wavelengths from different input fiber ports can be multiplexed into a common output fiber port. In addition, wavelength division multiplexed channels of arbitrary wavelength spacings can also be demultiplexed and dynamically routed into arbitrary output fiber ports. A proof-of-principle 1x3 adaptive multiplexer/demultiplexers is experimentally demonstrated. PMID- 20588353 TI - Digital phase conjugation of second harmonic radiation emitted by nanoparticles in turbid media. AB - We demonstrate focusing coherent light on a nanoparticle through turbid media based on digital optical phase conjugation of second harmonic generation (SHG) field from the nanoparticle. A SHG active nanoparticle inside a turbid medium was excited at the fundamental frequency and emitted SHG field as a point source. The SHG emission was scattered by the turbid medium, and the scattered field was recorded by off-axis digital holography. A phase-conjugated beam was then generated by using a phase-only spatial light modulator and sent back through the turbid medium, which formed a nearly ideal focus on the nanoparticle. PMID- 20588354 TI - Widely tunable dual-wavelength Er3+-doped fiber laser for tunable continuous-wave terahertz radiation. AB - We propose a widely tunable dual-wavelength Erbium-doped fiber laser that uses two micro-heater-integrated Fabry-Perot laser diodes (FP-LDs) and two fiber Bragg gratings (FBGs) for tunable continuous-wave (CW) terahertz (THz) radiation. Each wavelength can be independently tuned by using an FP-LD and an FBG. The wavelength fine tuning is achieved by simultaneously applying current to the micro-heater on the FP-LD and strain to the FBG. The side-mode suppression ratio is more than 35 dB for both wavelengths. The wavelength spacing of the dual wavelength can be continuously tuned from 3.2 nm to 9.6 nm. Continuous frequency tuning of the CW THz radiation is also successfully achieved using an InGaAs based photomixer with our dual-wavelength fiber laser as the optical beat source. The emitted CW THz radiation is continuously tuned from 0.3 to 0.8 THz. PMID- 20588355 TI - Giant enhancement of second-harmonic generation in multiple diffraction orders from sub-wavelength resonant waveguide grating. AB - We demonstrate a purely dielectric resonant waveguide structure that enhances the efficiency of second-harmonic generation by a factor of at least 5500 compared to a flat reference surface in the same geometry. We also show that the structure emits second-harmonic radiation in four different directions when the sample is illuminated with fundamental radiation incident at the resonant angle of the sample. PMID- 20588356 TI - MTF of compound eye. AB - Compound eye is a new field of research about miniaturizing imaging systems. We for the first time introduce a dual compound eye that contains three micro lens arrays with aspheric surfaces. The designed dual compound eye in one state is a superposition system in which each channel images all of field of view of the system. With adding a field stop we have decreased the stray light. MTF of ideal superposition compound eye calculated. Also with changing field stop the system is converted to an apposition compound eye in which each channel images only a part of total field of view and so the field of view is larger than that of superposition type. PMID- 20588357 TI - Design of high-energy terahertz sources based on optical rectification. AB - Detailed analysis of the tilted-pulse-front pumping scheme used for ultrashort THz pulse generation by optical rectification of femtosecond laser pulses is presented. It is shown that imaging errors in a pulse-front-tilting setup consisting of a grating and a lens can lead to a THz beam with strongly asymmetric intensity profile and strong divergence, thereby limiting applications. Optimized setup parameters are given to reduce such distortions. We also show that semiconductors can offer a promising alternative to LiNbO(3) in high-energy THz pulse generation when pumped at longer wavelengths. This requires tilted-pulse-front pumping, however the small tilt angles allow semiconductors to be easily used in such schemes. Semiconductors can be advantageous for generating THz pulses with high spectral intensity at higher THz frequencies, while LiNbO(3) is better suited to generate THz pulses with very large relative spectral width. By using optimized schemes the upscaling of the energy of ultrashort THz pulses is foreseen. PMID- 20588358 TI - Enhanced extended range underwater imaging via structured illumination. AB - In this article, the utility of structured illumination in order to enhance the contrast and subsequent range capability of an underwater imaging system is explored. The proposed method consists of transmitting a short pulse of light in a grid like pattern that consists of multiple, narrow, delta-function like beams. The grid pattern can be arranged in either a one-dimensional line or an area as a two-dimensional pattern. Scanning the pattern in time results in the sequential illumination of the entire scene. The receiving system architecture imposes the exact same, grid-like pattern sensitivity on the reflected light with a simple subsequent superposition of the time-sequenced images. The system can be viewed as a parallel implementation of a Laser Line Scan System where multiple beams are projected and received instead of a single one. The performance enhancement over more conventional systems that project either a sheet or an area of light is compared for a challenging underwater environment via computer simulations. The resulting images are analyzed as a function of the spacing between the projected light beams to characterize contrast and resolution. The results indicate that reasonable gains are obtainable for close spacing between the beams while quite significant gains are predicted for larger ones. Structured illumination systems can therefore collect images more rapidly than systems that scan a single beam; however with concomitant trade-offs in contrast and resolution. PMID- 20588359 TI - Distortionless large-ratio stretcher for ultra-short pulses using photonic crystal fiber. AB - A large-ratio stretcher for ultra-short pulses is proposed based on photonic crystal fiber (PCF). Through proper design of the PCF structure, we obtain over 300-nm wavelength range with flattened dispersion characteristics. Analysis indicates that 1-km of such fiber can broaden over 10,000 times for ultra-short pulses with <100-fs pulse-width. Distortion due to dispersion and nonlinearity is negligible. PMID- 20588360 TI - Intra-connected three-dimensionally isotropic bulk negative index photonic metamaterial. AB - Isotropic negative index metamaterials (NIMs) are highly desired, particularly for the realization of ultra-high resolution lenses. However, existing isotropic NIMs function only two-dimensionally and cannot be miniaturized beyond microwaves. Direct laser writing processes can be a paradigm shift toward the fabrication of three-dimensionally (3D) isotropic bulk optical metamaterials, but only at the expense of an additional design constraint, namely connectivity. Here, we demonstrate with a proof-of-principle design that the requirement connectivity does not preclude fully isotropic left-handed behavior. This is an important step towards the realization of bulk 3D isotropic NIMs at optical wavelengths. PMID- 20588361 TI - Direct measurement of cyclotron coherence times of high-mobility two-dimensional electron gases. AB - We have observed long-lived (approximately 30 ps) coherent oscillations of charge carriers due to cyclotron resonance (CR) in high-mobility two-dimensional electrons in GaAs in perpendicular magnetic fields using time-domain terahertz spectroscopy. The observed coherent oscillations were fitted well by sinusoids with exponentially-decaying amplitudes, through which we were able to provide direct and precise measures for the decay times and oscillation frequencies simultaneously. This method thus overcomes the CR saturation effect, which is known to prevent determination of true CR linewidths in high-mobility electron systems using Fourier-transform infrared spectroscopy. PMID- 20588362 TI - All-optical memory operation of 980-nm polarization bistable VCSEL for 20-Gb/s PRBS RZ and 40-Gb/s NRZ data signals. AB - The fastest known operation of all-optical flip-flop memory was experimentally demonstrated using a 980-nm polarization bistable vertical-cavity surface emitting laser (VCSEL). Operating conditions of the input signal power and the frequency detuning to achieve the fast optical memory operation were characterized experimentally. At the optimum condition, 1-bit data signals were arbitrarily sampled and memorized from a 2(6)-1 pseudorandom bit sequence return to-zero signal at 20 Gb/s by using AND gate and memory functionalities obtained from the polarization bistability. In addition, 1-bit memory operation was achieved for a 6-bit non-return-to-zero signal at 40 Gb/s. Both memory operations required 250-microW data signal power and had optical gain. The high potential of all-optical flip-flop memories based on polarization bistable VCSELs for use in ultrafast all-optical future networks was demonstrated. PMID- 20588363 TI - Theoretical calculation and experimental study of acousto-optically Q-switched CO2 laser. AB - Using resonator inserted with acousto-optically modulator, the experiments of the compacted CO(2) laser were performed with Q-switch. According to various factors that influenced the output of laser, the theoretical calculation of its main parameters was conducted by Q-switched pulsed laser rate equations. Based on the results, the technical route and approach were presented for optimization design of this laser. The measured peak power of this laser device was more than 4000W and pulsed width was 180ns which agreed well with the theoretical calculation. The range of repetition frequency could adjust from 1 Hz to 100 kHz. The theoretical analyzes and experimental results showed that the acoustic traveling time of ultrasonic field could not influence the pulse width of laser so that it did not require inserting optical lens in the cavity to reduce the diameter of beam. The acoustic traveling time only extended the establishingtime of laser pulse. The optimum working frequency of laser is about 1 kHz, which it matched with the radiation life time (1 ms) of CO(2) molecular upper energy level. When the frequency is above 1 kHz, the pulse width of laser increased with the frequency. The full band of wavelength tuning between 9.2 microm and 10.8 microm was obtained by grating selection one by one which the measured spectrum lines were over 30 in the condition of Q-switch. PMID- 20588364 TI - Matched cascade of bandgap-shift and frequency-conversion using stimulated Raman scattering in a tapered hollow-core photonic crystal fibre. AB - We report on a novel means which lifts the restriction of the limited optical bandwidth of photonic bandgap hollow-core photonic crystal fiber on generating high order stimulated Raman scattering in gaseous media. This is based on H(2) filled tapered HC-PCF in which the taper slope is matched with the effective length of Raman process. Raman orders outside the input-bandwidth of the HC-PCF are observed with more than 80% quantum-conversion using a compact, low-power 1064 nm microchip laser. The technique opens prospects for efficient sources in spectral regions that are poorly covered by currently existing lasers such as mid IR. PMID- 20588365 TI - Highly nonlinear hybrid AsSe-PMMA microtapers. AB - We report the fabrication and characterization of an AsSe microtaper with a protective cladding made of PolyMethyl MethAcrylate (PMMA). The AsSe core of the microtaper provides an ultrahigh nonlinearity up to gamma = 133 W(-1)m(-1) whereas the polymer cladding provides mechanical strength for normal handling of the device and reduces sensitivity to the surrounding environment. PMID- 20588366 TI - Fourier domain Pump-Probe Optical Coherence Tomography imaging of melanin. AB - We report the development of a two-color Fourier domain Pump-Probe Optical Coherence Tomography (PPOCT) system. Tissue phantom experiments to characterize the system performance demonstrated imaging depths in excess of 725 microm, nearly comparable to the base Optical Coherence Tomography system. PPOCT A-line rates were also demonstrated in excess of 1 kHz. The physical origin of the PPOCT signal was investigated with a series of experiments which revealed that the signal is a mixture of short and long lifetime component signals. The short lifetime component was attributed to transient absorption while the long lifetime component may be due to a mixture of transient absorption and thermal effects. Ex vivo images of porcine iris demonstrated the potential for imaging melanin in the eye, where cancer of the melanocytes is the most common form of eye cancer in adults. PMID- 20588367 TI - Raman beam cleanup in silicon in the mid-infrared. AB - We report evidence of beam cleanup during stimulated Raman scattering in silicon. An amplified near-diffraction-limited Stokes beam is obtained from a severely aberrated pump beam. PMID- 20588368 TI - Demonstration of optical steganography transmission using temporal phase coded optical signals with spectral notch filtering. AB - A novel approach is proposed and experimentally demonstrated for optical steganography transmission in WDM networks using temporal phase coded optical signals with spectral notch filtering. A temporal phase coded stealth channel is temporally and spectrally overlaid onto a public WDM channel. Direct detection of the public channel is achieved in the presence of the stealth channel. The interference from the public channel is suppressed by spectral notching before the detection of the optical stealth signal. The approach is shown to have good compatibility and robustness to the existing WDM network for optical steganography transmission. PMID- 20588369 TI - Hybrid metamaterial design and fabrication for terahertz resonance response enhancement. AB - Planar hybrid metamaterial with different split ring resonators (SRR) structure dimensions are fabricated on silicon substrates by femtosecond (fs) laser micro lens array (MLA) lithography and lift-off process. The fabricated metamaterial structures consist of: (a) uniform metamaterial with 4 SRRs at same design and dimension as a unit cell and (b) hybrid metamaterial with 4 SRRs at same design but different dimensions as a unit cell. The electromagnetic field responses of these hybrid and single dimension metamaterial structures are characterized using a terahertz (THz) time-domain spectroscopy. Transmission spectra of these metamaterial show that a broader resonance peak is formed when 2 SRRs are close to each other. FDTD simulation proves that there is a strong mutual coupling between 2 SRRs besides a strong localized electric field at the split gap, which can enhance the electric field up to 364 times for tunable, broad band and high sensitivity THz sensing. Meanwhile, the strong coupling effect could lead to the formation of an additional resonance peak at approximately 0.2 THz in the THz spectra regime. PMID- 20588370 TI - A novel adaptive mechanical-wetting lens for visible and near infrared imaging. AB - We demonstrate an adaptive mechanical-wetting lens with a concentric reservoir to reduce image aberrations and overcome the gravity effect. This lens adopts liquid pressure to change the interface between two immiscible liquids which, in turn, changes the focal length of the resultant liquid lens. Good optical performance, high resolution, and a wide dynamic range of both positive and negative optical power are achieved. Since no PDMS is employed, such lenses can extend their working range to infrared region by choosing proper liquids. PMID- 20588371 TI - Fluorescence spectra of atmospheric aerosol particles measured using one or two excitation wavelengths: comparison of classification schemes employing different emission and scattering results. AB - An improved Dual-wavelength-excitation Particle Fluorescence Spectrometer (DPFS) has been reported. It measures two fluorescence spectra excited sequentially by lasers at 263 nm and 351 nm, from single atmospheric aerosol particles in the 1 10 mum diameter size range. Here we investigate the different levels of discrimination capability obtained when different numbers of excitation and fluorescence-emission wavelengths are used for analysis. We a) use the DPFS to measure fluorescence spectra of Bacillus subtilis and other aerosol particles, and a 25-hour sample of atmospheric aerosol at an urban site in Maryland, USA; b) analyze the data using six different algorithms that employ different levels of detail of the measured data; and c) show that when more of the data measured by the DPFS is used, the ability to discriminate among particle types is significantly increased. PMID- 20588372 TI - Highly flexible MTF measurement system for tunable micro lenses. AB - We present an efficient, low-cost modulation transfer function (MTF) measurement approach, optimized for characterization of tunable micro-lenses; the MTF may easily be measured at a variety of different focal lengths. The approach uses a conventional optical microscope with an optimized approach for lens illumination and the measurement results have been correlated with a commercial MTF measurement system. Measurements on fixed-focus and tunable micro-lenses were performed; for the latter, resolution for lenses with back focal length of 11 mm was 55 lines/mm, decreasing to 40 lines/mm for a back focal length of 4 mm. In general, it was seen that performance was better for lenses with longer focal lengths. PMID- 20588373 TI - Long-range surface magnetoplasmon on thin plasmon films in the Voigt configuration. AB - This study elucidates the characteristics of a long-range surface magnetoplasmon (LRSMP) that propagates on a plasmon film with the Voigt configuration. Particle in-cell (PIC) simulations and theoretical analyses are performed. Simulation results indicate that LRSMP has non-symmetrical fields. The proposed scheme also verifies the non-reciprocal properties of LRSMP as the direction of an applied external magnetic field is reversed. When surface waves propagate on a plasmon film across an interface on one side of which long-range surface plasmon (LRSP) is allowed while on the other side of which LRSMP is allowed, the interface behaves similar to a defect and transforms the surface waves into radiation modes owing to the mismatch between the field patterns of LRSP and LRSMP. Furthermore, PIC simulation results confirm the presence of a new high-frequency LRSMP whose frequency exceeds the plasma frequency and lacks a LRSP counterpart. PMID- 20588374 TI - Large dynamic resonance transition between surface plasmon and localized surface plasmon modes. AB - We present resonant terahertz transmission in a composite plasmonic film comprised of an array of subwavelength metallic patches and semiconductor holes. A large dynamic transition between a dipolar localized surface plasmon mode and a surface plasmon resonance near 0.8 THz is observed under near infrared optical excitation. The reversal in transmission amplitude from a stop-band to a pass band and up to pi/2 phase shift achieved in the composite plasmonic film make it promising in large dynamic phase modulation, optical changeover switching, and active terahertz plasmonics. PMID- 20588375 TI - Spontaneous decay of a single quantum dot coupled to a metallic slot waveguide in the presence of leaky plasmonic modes. AB - We numerically investigate the coupling efficiency of a single self-assembled quantum dot to a metallic slot waveguide in the presence of leaky plasmonic modes. Leaky plasmonic modes refer to radiation modes with plasmonic features, resulting from the inhomogeneity of the dielectric environment in which the metallic slot waveguide is embedded. Compared to the ideal case of a homogenous dielectric environment, the coupling efficiency of an emitter to a metallic slot waveguide is significantly reduced. We attribute the reduction to the coupling to leaky plasmonic modes. By increasing the refractive index of the coating layer to minimize the impacts from the leaky plasmonic modes, we find that the coupling efficiency of the quantum dot to the single mode supported by the metallic slot waveguide can be enhanced by more than a factor 2. PMID- 20588376 TI - Highly efficient 750 W tapered double-clad ytterbium fiber laser. AB - The results of theoretical and experimental studies of active tapered double-clad fibers, intending the optimization of its imperative parameters--tapering ratio, longitudinal profile, core/cladding diameters ratio, are presented. Using a refined taper geometry we have demonstrated power scaling of a ytterbium fiber laser pumped by low-brightness, cost-effective laser diodes up to 750 W, with 80% efficiency. PMID- 20588377 TI - Implantable semiconductor biosensor for continuous in vivo sensing of far-red fluorescent molecules. AB - We have fabricated miniature implantable fluorescence sensors for continuous fluorescence sensing applications in living subjects. These monolithically integrated GaAs-based sensors incorporate a 675 nm vertical-cavity surface emitting laser (VCSEL), a GaAs PIN photodiode, and a fluorescence emission filter. We demonstrate high detection sensitivity for Cy5.5 far-red dye (50 nanoMolar) in living tissue, limited by the intrinsic background autofluorescence. These low cost, sensitive and scalable sensors are promising for long-term continuous monitoring of molecular dynamics for biomedical studies in freely moving animals. PMID- 20588378 TI - Natural quasy-periodic binary structure with focusing property in near field diffraction pattern. AB - A naturally-inspired phase-only diffractive optical element with a circular symmetry given by a quasi-periodic structure of the phyllotaxis type is presented in this paper. It is generated starting with the characteristic parametric equations which are optimal for the golden angle interval. For some ideal geometrical parameters, the diffracted intensity distribution in near-field has a central closed ring with almost zero intensity inside. Its radius and intensity values depend on the geometry or non-binary phase distribution superposed onto the phyllotaxis geometry. Along propagation axis, the transverse diffraction patterns from the binary-phase diffractive structure exhibit a self-focusing behavior and a rotational motion. PMID- 20588379 TI - NLFM waveform generation using tunable integrated optical ring resonators: simulation and proof of concept experiment. AB - The NLFM waveform resulting from a tunable integrated optical ring resonator is simulated. The metrics of interest are the first sidelobe levels and FWHM times of the autocorrelation, as these directly relate to the long-range performance and fine range resolution of a LADAR system, and should ideally be as small as possible. Through simulation, the maximum sidelobe level of the autocorrelation of an NLFM waveform generated by a series of tunable integrated optical ring resonators is shown to be -20 to -30 dB or lower. A proof of concept experiment employing an off-the-shelf thermally tunable silicon-nitride optical ring resonator is shown to generate NLFM chirped waveforms with a bandwidth of 28 kHz. PMID- 20588380 TI - Optical properties of red emitting self-assembled InP/(Al0.20Ga0.80)0.51In0.49P quantum dot based micropillars. AB - Using focused ion beam etching techniques, micropillar cavities were fabricated from a high reflective AlAs/AlGaAs distributed Bragg reflector planar cavity containing self-assembled InP quantum dots in (Al(0.20)Ga(0.80))(0.51)In(0.49)P barrier layers. The mode spectra of pillars with different diameters were investigated using micro-photoluminescence, showing excellent agreement with theory. Quality factors of the pillar cavities up to 3650 were observed. Furthermore, for a microcavity pillar with 1.26 mum diameter, single-photon emission is demonstrated by performing photon correlation measurements under pulsed excitation. PMID- 20588381 TI - Transport of Intensity phase-amplitude imaging with higher order intensity derivatives. AB - We demonstrate a method for improving the accuracy of phase retrieval based on the Transport of Intensity equation by using intensity measurements at multiple planes to estimate and remove the artifacts due to higher order axial derivatives. We suggest two similar methods of higher order correction, and demonstrate their ability for accurate phase retrieval well beyond the 'linear' range of defocus that TIE imaging traditionally requires. Computation is fast and efficient, and sensitivity to noise is reduced by using many images. PMID- 20588382 TI - Alignment-to-polarization projection in dye-doped nematic liquid crystal microlasers. AB - We report a dye-doped nematic liquid crystal microlaser that allows the two dimensional alignment of the liquid crystal to be projected directly on the output polarization of the laser beam. The laser cavity is composed of a pair of dielectric multilayers sandwiching a dye-doped nematic liquid crystal with patterned alignment, and exploits the fact that the resonance modes in such systems are split into two orthogonally polarized modes experiencing either the extraordinary or ordinary refractive index of the liquid crystal. Azimuthally polarized lasing is demonstrated using a concentrically aligned liquid crystal layer. PMID- 20588383 TI - Influence of carrier transport on Raman amplification in silicon waveguides. AB - This paper analyze for the first time the impact of the charge carrier transport on the continuously pumped stimulated Raman amplification in silicon waveguides. A novel analytical model is developed using which the coupled differential equations of the pump and the probe optical signals and those of carrier transport are solved concurrently. The simulation and analysis suggest that the neglect of the carrier transport phenomenon, reported in the previously published works, is approximately justified only if the effective carrier lifetime is comparable to the carrier transit time, otherwise it can result in substantial overestimation of the free carrier density at the optical mode center. PMID- 20588384 TI - Mechanism of depolarization of white light generated by femtosecond laser pulse in water. AB - The polarization state of the white light produced by a femtosecond laser pulse through a water cell is investigated. The depolarization of the white light was found to be induced by magnification of the polarization perturbation in the incident light which is caused by the focus lens. Cross-phase modulation (XPM) of the third order nonlinear polarization is proposed as the depolarization mechanism. PMID- 20588385 TI - Propagation factor of a stochastic electromagnetic Gaussian Schell-model beam. AB - Analytical formula is derived for the propagation factor (known asM(2)-factor) of a stochastic electromagnetic Gaussian Schell-model (EGSM) beam in free space and in turbulent atmosphere. In free space, the M(2)-factor of an EGSM beam is mainly determined by its initial degree of polarization, r.m.s. widths of the spectral densities and correlation coefficients, and its value remains invariant on propagation. In turbulent atmosphere, the M(2)-factor of an EGSM beam is also determined by the parameters of the turbulent atmosphere, and its value increases on propagation. The relative M(2)-factor of an EGSM beam with lower correlation factors, larger r.m.s. widths of the spectral densities and longer wavelength is less affected by the atmospheric turbulence. Under suitable conditions, an EGSM beam is less affected by the atmospheric turbulence than a scalar GSM beam (i.e. fully polarized GSM beam). Our results will be useful in long-distance free-space optical communications. PMID- 20588386 TI - Advanced and delayed images through an image resonator. AB - We performed optical image propagation experiments in an image resonator consisting of a Fabry-Perot resonator in reflection geometry. Two-dimensional images encoded on optical pulses of 32ns were stored, and either advanced, 6.0ns, or delayed, 10.9ns, using the dispersion relation relevant to the image resonator, in the under- or over- coupling condition, respectively. The overall images are propagated through the resonator clearly, while the diffraction effects were analyzed both in real-space and in k-space. PMID- 20588387 TI - Planar high-numerical-aperture low-loss focusing reflectors and lenses using subwavelength high contrast gratings. AB - We propose planar, high numerical aperture (NA), low loss, focusing reflectors and lenses using subwavelength high contrast gratings (HCGs). By designing the reflectance and the phase of non-periodic HCGs, both focusing reflectors and lenses can be constructed. Numerical aperture values as high as 0.81 and 0.96 are achieved for a reflector and lens with very low losses of 0.3 and 0.2 dB, respectively. The design algorithm is also shown to be readily extended to a 2D lens. Furthermore, HCG optics can simultaneously focus the reflected and transmitted waves, with important technological implications. HCG focusing optics are defined by one-step photolithography and thus can be readily integrated with many devices including VCSELs, saturable absorbers, telescopes, CCDs and solar cells. PMID- 20588388 TI - Analysis of short range forces in opto-mechanical devices with a nanogap. AB - We employ the finite-difference time-domain method to calculate the dominant short range forces in optomechanical devices, Casimir and gradient optical forces. Numerical results are obtained for typical silicon optomechanical devices and are compared to metallic reference structures, taking into account geometric and frequency dispersion of silicon. Our results indicate that although a small gap is desirable for operating optomechanical devices, the Casimir force offsets the gradient force in strongly coupled optomechanical devices, which has to be taken into account in the design of optical force tunable devices. PMID- 20588389 TI - Enabling coherent superpositions of iso-frequency optical states in multimode fibers. AB - The ability to precisely and selectively excite superpositions of specific fiber eigenmodes allows one in principle to control the three dimensional field distribution along the length of a fiber. Here we demonstrate the dynamic synthesis and controlled transmission of vectorial eigenstates in a hollow core cylindrical photonic bandgap fiber, including a coherent superposition of two different angular momentum states. The results are verified using a modal decomposition algorithm that yields the unique complex superposition coefficients of the eigenstate space. PMID- 20588390 TI - A low-cost, portable, and quantitative spectral imaging system for application to biological tissues. AB - The ability of diffuse reflectance spectroscopy to extract quantitative biological composition of tissues has been used to discern tissue types in both pre-clinical and clinical cancer studies. Typically, diffuse reflectance spectroscopy systems are designed for single-point measurements. Clinically, an imaging system would provide valuable spatial information on tissue composition. While it is feasible to build a multiplexed fiber-optic probe based spectral imaging system, these systems suffer from drawbacks with respect to cost and size. To address these we developed a compact and low cost system using a broadband light source with an 8-slot filter wheel for illumination and silicon photodiodes for detection. The spectral imaging system was tested on a set of tissue mimicking liquid phantoms which yielded an optical property extraction accuracy of 6.40 +/- 7.78% for the absorption coefficient (micro(a)) and 11.37 +/ 19.62% for the wavelength-averaged reduced scattering coefficient (micro(s)'). PMID- 20588391 TI - Electrically controlled multifrequency ferroelectric cloak. AB - We have suggested an electrically controlled multifrequency cloak with a single shell of ferroelectric material for the first time to the best of our knowledge. The theoretical and simulated results have demonstrated that this cloak with high index ferroelectrics can reduce the total scattering cross section of the cloaked system at multiple frequencies. These cloaking frequencies of our cloak can be externally controlled since the dielectric constant of ferroelectrics is well tuned with the applied electric field. It may provide a potential way to design a tunable multifrequency cloak with considerable flexibility. PMID- 20588392 TI - Suppression of local haze variations in MERIS images over turbid coastal waters for retrieval of suspended sediment concentration. AB - Atmospheric correction over turbid waters can be problematic if atmospheric haze is spatially variable. In this case the retrieval of water quality is hampered by the fact that haze variations could be partly mistaken for variations in suspended sediment concentration (SSC). In this study we propose the suppression of local haze variations while leaving sediment variations intact. This is accomplished by a multispectral data projection (MDP) method based on a linear spectral mixing model, and applied prior to the actual standard atmospheric correction. In this linear model, the hazesediment spectral mixing was simulated by a coupled water-atmosphere radiative transfer (RT) model. As a result, local haze variations were largely suppressed and transformed into an approximately homogenous atmosphere over the MERIS top-of-atmosphere (TOA) radiance scene. The suppression of local haze variations increases the number of satellite images that are still suitable for standard atmospheric correction processing and subsequent water quality analysis. PMID- 20588393 TI - Nonlinear mirror modelocking of a bounce geometry laser. AB - We present the investigation of nonlinear mirror modelocking (NLM) of a bounce amplifier laser. This technique, a potential rival to SESAM modelocking, uses a nonlinear crystal and a dichroic mirror to passively modelock a Nd:GdVO(4) slab bounce amplifier operating at 1063nm. At 11.3W, we present the highest power achieved using the NLM technique, using type-II phase-matched KTP, with a pulse duration of 57ps. Using type-I phase-matched BiBO, modelocking was achieved with a shorter pulse duration of 5.7ps at an average power of 7.1W. PMID- 20588394 TI - Improving the efficiency of an optical parametric oscillator by tailoring the pump pulse shape. AB - The conversion efficiency of an optical parametric oscillator is reduced by energy consumption during build-up of signal and idler intensities and due to back-conversion effects. By tailoring the pump pulse temporal shape, we are able to improve the conversion efficiency by minimizing build-up time and back conversion. Simulations predict a significant improvement in 1064 nm to 4000 nm idler conversion by using a double-rectangular temporal shape rather than using a simple Gaussian pulse. Experimental results qualitatively verify the effect resulting in a 20% improvement of a rectangular pulse over a Gaussian pulse. PMID- 20588395 TI - White light reconstruction of image plane digital holograms. AB - A real-time system is developed that employs a CCD sensor for recording and a reflective high-resolution liquid crystal display for reconstructing of image plane digital holograms. Two types of light sources, namely, the coherent (laser) and white light (LED) are used for optical reconstructions of static and dynamic object wave fronts. As expected, white light reconstructions exhibit improved properties compared to the corresponding monochrome reconstructions. However, these improvements become substantial in cases in which digital holograms are preprocessed by applying the common algebraic operations such as subtraction. PMID- 20588396 TI - Type-0 second order nonlinear interaction in monolithic waveguides of isotropic semiconductors. AB - We report the observation of type-0 phase-matching in bulk z-grown Al(x)Ga(1-x)As Bragg reflection waveguides where TM-polarized second-harmonic is generated using TM-polarized pump. For a pulsed pump with 1.8 ps temporal width and an average power of 3.3 mW, secondharmonic power of 16 microW was detected at 1567.8 nm. The normalized nonlinear conversion efficiency was obtained to be 2.84 x 10(3) %W( 1)cm(-2) in a 2.2 mm long waveguide. The highly versatile modal birefringence in Bragg reflection waveguides enabled the phase-matching of the three modalities; namely type-0 TM(omega)-->TM(2omega), type-I TE(omega)-->TM(2omega) and type-II TE(omega)+TMomega-->TE(2omega) interactions to simultaneously take place within a spectral bandwidth as small as 17 nm. PMID- 20588397 TI - Ion-exchanged Er3+/Yb3+ co-doped waveguide amplifiers longitudinally pumped by broad area lasers. AB - A multimode pumping scheme for Er(3+)/Yb(3+) co-doped waveguide amplifiers based on broad area lasers at around 980 nm is presented. The proposed amplifier is fabricated by ion-exchange (IE) technique on silicate and phosphate glasses. The highly efficient energy transfer from Yb(3+) to Er(3+) ions, combined with the use of low cost and high power broad area laser, allows the realization of high performance and cost-effective integrated amplifiers. The structure has been designed and numerically studied using a 3D finite element modelling tool, and over 3 dB/cm small signal gain has been predicted for an optimized amplifier. Preliminary characterization of an amplifier structure provides a first experimental evidence of the novel multimode longitudinal pumping. PMID- 20588398 TI - System feasibility of using stimulated Brillouin scattering in self coherent detection schemes. AB - We demonstrate the first self-coherent detection of 10 Gbit/s BPSK signals based on narrow-band amplification of the optical carrier by means of Stimulated Brillouin effect in a common fiber. We found that this technique is very effective only if it is combined with proper line coding and high-pass electrical filtering at the receiver. In this case we obtain OSNR-performance close to the ideal coherent receiver. PMID- 20588399 TI - Soliton mediated optical quantization in the transmission of one-dimensional photonic crystals. AB - We report the experimental and numerical observation of step-like behavior of the high-intensity transmission deep inside the bandgap of a 1D photonic crystal. We show this to be a novel manifestation of the quantization of the soliton area, and derive an upper limit for the energy of the transmission steps, which is consistent with measurements and simulations. PMID- 20588400 TI - High average and peak power few-cycle laser pulses delivered by fiber pumped OPCPA system. AB - We report on a high power optical parametric amplifier delivering 8 fs pulses with 6 GW peak power. The system is pumped by a fiber amplifier and operated at 96 kHz repetition rate. The average output power is as high as 6.7 W, which is the highest average power few-cycle pulse laser reported so far. When stabilizing the seed oscillator, the system delivered carrier-envelop phase stable laser pulses. Furthermore, high harmonic generation up to the 33(th) order (21.8 nm) is demonstrated in a Krypton gas jet. In addition, the scalability of the presented laser system is discussed. PMID- 20588401 TI - Measurements of nonlinear refractive index in scattering media. AB - We have recently developed a spectral re-shaping technique to simultaneously measure nonlinear refractive index and nonlinear absorption. In this technique, the information about the nonlinearities is encoded in the frequency domain, rather than in the spatial domain as in the conventional Z-scan method. Here we show that frequency encoding is much more robust with respect to scattering. We compare spectral re-shaping and Z-scan measurements in a highly scattering environment and show that reliable spectral re-shaping measurements can be performed even in a regime that precludes standard Z-scans. PMID- 20588402 TI - Toward a broadband astro-comb: effects of nonlinear spectral broadening in optical fibers. AB - We propose and analyze a new approach to generate a broadband astro-comb by spectral broadening of a narrowband astro-comb inside a highly nonlinear optical fiber. Numerical modeling shows that cascaded four-wave-mixing dramatically degrades the input comb's side-mode suppression and causes side-mode amplitude asymmetry. These two detrimental effects can systematically shift the center-of gravity of astro-comb spectral lines as measured by an astrophysical spectrograph with resolution approximately 100,000; and thus lead to wavelength calibration inaccuracy and instability. Our simulations indicate that this performance penalty, as a result of nonlinear spectral broadening, can be compensated by using a filtering cavity configured for double-pass. As an explicit example, we present a design based on an Yb-fiber source comb (with 1 GHz repetition rate) that is filtered by double-passing through a low finesse cavity (finesse = 208), and subsequent spectrally broadened in a 2-cm, SF6-glass photonic crystal fiber. Spanning more than 300 nm with 16 GHz line spacing, the resulting astro-comb is predicted to provide 1 cm/s (approximately 10 kHz) radial velocity calibration accuracy for an astrophysical spectrograph. Such extreme performance will be necessary for the search for and characterization of Earth-like extra-solar planets, and in direct measurements of the change of the rate of cosmological expansion. PMID- 20588403 TI - Transmission of 20-Gb/s OFDM signals occupying 7-GHz license-free band at 60 GHz using a RoF system employing frequency sextupling optical up-conversion. AB - This work describes a proposed 60-GHz radio-over-fiber (RoF) system employing a frequency sextupling optical up-conversion scheme. Based on the modified single sideband modulation scheme, spectrally efficient vector signals were transmitted with no performance degradation due to dispersion-induced fading. Wavelength division- multiplexed optical up-conversion can be realized using the proposed system. Since the required transmitter bandwidth is significantly reduced, radio frequency components with lower bandwidth and higher reliability can be utilized. Both 13.75-Gb/s QPSK-OFDM and 20.625-Gb/s 8QAM-OFDM signals were experimentally demonstrated. After transmission over 25-km of standard single mode fiber, no significant received power penalty was observed. PMID- 20588404 TI - The Offner imaging spectrometer in quadrature. AB - This is a proposal and description of a new configuration for an Offner imaging spectrometer based on the theory of aberrations of off-plane classical-ruled spherical diffraction gratings. This new spectrometer comprises a concave mirror used in double reflection and a convex reflection grating operating in quadrature, in a concentric layout. A very simple procedure obtains designs that are anastigmatic for a given point on the entrance slit and a given wavelength. Specific examples show that the performance of this type of system improves the performance of analogous conventional in-plane systems, when compactness and/or high spectral resolution is of fundamental importance. PMID- 20588405 TI - Negative refractive index in coaxial plasmon waveguides. AB - We theoretically show that coaxial waveguides composed of a metallic core, surrounded by a dielectric cylinder and clad by a metal outer layer exhibit negative refractive index modes over a broad spectral range in the visible. For narrow dielectric gaps (10 nm GaP embedded in Ag) a figure-of-merit of 18 can be achieved at lambda(0) = 460 nm. For larger dielectric gaps the negative index spectral range extends well below the surface plasmon resonance frequency. By fine-tuning the coaxial geometry the special case of n = -1 at a figure-of-merit of 5, or n = 0 for a decay length of 500 nm can be achieved. PMID- 20588406 TI - Guided modes near the Dirac point in negative-zero-positive index metamaterial waveguide. AB - Motivated by the realization of the Dirac point (DP) with a double-cone structure for optical field in the negative-zero-positive index metamaterial (NZPIM), we make theoretical investigations of the guided modes in the NZPIM waveguide near the DP by using the graphical method. Due to the linear Dirac dispersion, the fundamental mode is absent when the angular frequency is smaller than the DP, while the behaviors of NZPIM waveguide are similar to the conventional dielectric waveguide when the angular frequency is larger than the DP. The unique properties of the guided modes are analogous to the propagation of electron waves in graphene waveguide [Appl. Phys. Lett., 94, 212105 (2009)], corresponding to the classical motion and the Klein tunneling. These results suggest that many exotic phenomena in graphene can be simulated by the relatively simple optical NZPIM. PMID- 20588407 TI - Average enhancement factor of molecules-doped coreshell (Ag@SiO2) on fluorescence. AB - Average enhancement factor (AEF) of a coreshell (Ag@SiO(2)) on the fluorescence of molecules doped within the silica shell is proposed and studied to estimate the overall performance of a large number of coreshells. Using Mie theory and dyadic Green's functions, the enhancement factor (EF) of a coreshell is first calculated for any arbitrarily oriented and located electric dipole embedded in the shell. AEF is then obtained by averaging the individual EF over all possible orientations and positions of the electric dipoles. AEF of a FITC-doped coreshell (radius of Ag core: 25 nm, thickness of shell: 15 nm) irradiated by a laser of 488 nm for FITC's emission at 518 nm is 2.406. It is much smaller than the maximum EF (30.114) of a coreshell containing a single molecule with a radial orientation at its optimal position. For Alexa 430-doped coreshell excited at 428 nm, AEF is 12.34 at the emission of 538 nm. PMID- 20588408 TI - Design of multiplexed phase diffractive optical elements for focal depth extension. AB - A more computationally tractable method to design a multiplexed phase diffractive optical element with optical design software to extend the depth of focus is proposed, through which the intensity distribution of the output beams can also be controlled with great flexibility. The design principle is explained in detail. And the feasibility of this design method is illustrated through a design example followed by computer simulation verification. PMID- 20588409 TI - Surface plasmon-enhanced and quenched two-photon excited fluorescence. AB - This study investigated theoretically and experimentally that two-photon excited fluorescence is enhanced and quenched via surface plasmons (SPs) excited by total internal reflection with a silver film. The fluorescence intensity is fundamentally affected by the local electromagnetic field enhancement and the quantum yield change according to the surrounding structure and materials. By utilizing the Fresnel equation and classical dipole radiation modeling, local electric field enhancement, fluorescence quantum yield, and fluorescence emission coupling yield via SPs were theoretically analyzed at different dielectric spacer thicknesses between the fluorescence dye and the metal film. The fluorescence lifetime was also decreased substantially via the quenching effect. A two-photon excited total internal reflection fluorescence (TIRF) microscopy with a time correlated single photon counting device has been developed to measure the fluorescence lifetimes, photostabilities, and enhancements. The experimental results demonstrate that the fluorescence lifetimes and the trend of the enhancements are consistent with the theoretical analysis. The maximum fluorescence enhancement factor in the surface plasmon-total internal reflection fluorescence (SP-TIRF) configuration can be increased up to 30 fold with a suitable thickness SiO(2) spacer. Also, to compromise for the fluorescence enhancement and the fluorophore photostability, we find that the SP-TIRF configuration with a 10 nm SiO(2) spacer can provide an enhanced and less photobleached fluorescent signal via the assistance of enhanced local electromagnetic field and quenched fluorescence lifetime, respectively. PMID- 20588410 TI - Focusing properties of Fresnel zone plates with spiral phase. AB - Focusing properties of Fresnel zone plates with spiral phase with integer and fractional topological charges illuminated by plane wave are studied. Numerical results show that hollow beams can be generated and can also be controlled by the number of the zones and the topological charge, which implies the potential applications of such kind of zone plate in trapping and manipulating particles. PMID- 20588411 TI - Moment-based estimation for the shape parameters of the Gamma-Gamma atmospheric turbulence model. AB - We study the parameter estimation problem for the Gamma-Gamma turbulence model for free-space optical communication. An estimation scheme for the shape parameters of the Gamma-Gamma distribution is proposed based on the concept of fractional moments and convex optimization. To improve the estimation performance, we further propose a modified scheme which exploits the relationship between the Gamma-Gamma shape parameters in free-space optical communication. Simulation results reveal that the modified estimation scheme can achieve satisfactory performance for a wide range of turbulence conditions. PMID- 20588412 TI - Dual-wavelength mode-locked quantum-dot laser, via ground and excited state transitions: experimental and theoretical investigation. AB - We report a dual-wavelength passive mode locking regime where picosecond pulses are generated from both ground (lambda = 1263 nm) and excited state transitions (lambda = 1180 nm), in a GaAs-based monolithic two-section quantum-dot laser. Moreover, these results are reproduced by numerical simulations which provide a better insight on the dual-wavelength mode-locked operation. PMID- 20588413 TI - Propagation of laser radiation in a medium with thermally induced birefringence and cubic nonlinearity. AB - A system of differential equations describing, neglecting diffraction, the propagation of laser radiation in a medium with birefringence and cubic nonlinearity is derived. It is shown that the efficiency of depolarization compensation by means of a 90 degrees polarization rotator or a Faraday mirror decreases with increasing B-integral (nonlinear phase incursion). Comparison of the effectiveness of the considered method in the case of incident linear and circular polarization showed that for the circular polarization the optimal angle of polarization rotator is different from 90 degrees and the degree of polarization is less than for the linear one. PMID- 20588414 TI - Broadband NIR photoluminescence from Bi-doped Ba2P2O7 crystals: insights into the nature of NIR-emitting Bismuth centers. AB - We report on a novel type of Bi-doped crystal that exhibits ultrabroadband photoluminescence in the near infrared (NIR). Emission centers can be generated and degenerated reversibly by annealing the material in CO atmosphere and air, respectively, indicating that emission is related to the presence of Bi-species in low valence states. Correlating static and dynamic excitation and emission data with the size and charge of available lattice sites suggests that two types of Bi(0)-species, each located on one of the two available Ba(2+) lattice sites, are responsible for NIR photoemission. This is further confirmed by the absence of NIR emission in polycrystalline Ca(2)P(2)O(7):Bi and Sr(2)P(2)O(7):Bi. Excitation is assigned to transitions between the doubly degenerated ground state (4)S(3/2) and the degenerated excited levels (2)D(3/2), (2)D(5/2) and (2)P(1/2), respectively. NIR emission is attributed to (2)D(3/2)?(4)S(3/2). The NIR emission center can coexist with Bi(2+) species. Then, also Bi(2+) is accommodated on one of the two Ba(2+)-sites. Energy transfer between Bi(2+) ions occurs within a critical distance of 25.9 A. PMID- 20588415 TI - Experimental generating the partially coherent and partially polarized electromagnetic source. AB - The technique for generating the partially coherent and partially polarized source starting from the completely coherent and completely polarized laser source is proposed and analyzed. This technique differs from the known ones by the simplicity of its physical realization. The efficiency of the proposed technique is illustrated with the results of physical experiment in which an original technique for characterizing the coherence and polarization properties of the generated source is employed. PMID- 20588416 TI - High order statistics based blind deconvolution of bi-level images with unknown intensity values. AB - We propose a novel linear blind deconvolution method for bi-level images. The proposed method seeks an optimal point spread function and two parameters that maximize a high order statistics based objective function. Unlike existing minimum entropy deconvolution and least squares minimization methods, the proposed method requires neither unrealistic assumption that the pixel values of a bi-level image are independently identically distributed samples of a random variable nor tuning of regularization parameters.We demonstrate the effectiveness of the proposed method in simulations and experiments. PMID- 20588417 TI - Resonant-cavity-enhanced mid-infrared photodetector on a silicon platform. AB - In this paper, we demonstrate high optical quantum efficiency (90%) resonant cavity-enhanced mid-infrared photodetectors fabricated monolithically on a silicon platform. High quality photoconductive polycrystalline PbTe film is thermally evaporated, oxygen-sensitized at room temperature and acts as the infrared absorber. The cavity-enhanced detector operates in the critical coupling regime and shows a peak responsivity of 100 V/W at the resonant wavelength of 3.5 microm, 13.4 times higher compared to blanket PbTe film of the same thickness. Detectivity as high as 0.72 x 10(9) cmHz(1/2)W(-1) has been measured, comparable with commercial polycrystalline mid-infrared photodetectors. As low temperature processing (< 160 degrees C) is implemented in the entire fabrication process, our detector is promising for monolithic integration with Si readout integrated circuits. PMID- 20588418 TI - Electron beam excitation assisted optical microscope with ultra-high resolution. AB - We propose electron beam excitation assisted optical microscope, and demonstrated its resolution higher than 50 nm. In the microscope, a light source in a few nanometers size is excited by focused electron beam in a luminescent film. The microscope makes it possible to observe dynamic behavior of living biological specimens in various surroundings, such as air or liquids. Scan speed of the nanometric light source is faster than that in conventional near-field scanning optical microscopes. The microscope enables to observe optical constants such as absorption, refractive index, polarization, and their dynamic behavior on a nanometric scale. The microscope opens new microscopy applications in nano technology and nano-science. PMID- 20588419 TI - UV patterned nanoporous solid-liquid core waveguides. AB - Nanoporous Solid-Liquid core waveguides were prepared by UV induced surface modification of hydrophobic nanoporous polymers. With this method, the index contrast (deltan = 0.20) is a result of selective water infiltration. The waveguide core is defined by UV light, rendering the exposed part of a nanoporous polymer block hydrophilic. A propagation loss of 0.62 dB/mm and a bend loss of 0.81 dB/90 degrees for bend radius as low as 1.75 mm was obtained in these multimode waveguides. PMID- 20588420 TI - Low threshold lasing from dye-doped cholesteric liquid crystal multi-layered structures. AB - We fabricated novel hybrid structures composed of a dye-doped low-molecular weight cholesteric liquid crystal sandwiched by multi-layered polymer cholesteric liquid crystal films and evaluated their lasing characteristics. Lasing was observed with an extremely reduced threshold (12 nJ/pulse) by a factor of 10 compared with that in a simple dye-doped low-molecular-weight cholesteric liquid crystal cell. Lasing characteristics experimentally obtained were discussed by comparing them with the simulated photonic density of states spectra. PMID- 20588421 TI - Testing ultrafast two-photon spectral amplitudes via optical fibres. AB - We test two-dimensional TPSA of biphoton light emitted via ultrafast spontaneous parametric down-conversion (SPDC) using the effect of group-velocity dispersion in optical fibres. Further, we apply this technique to demonstrate the engineering of biphoton spectral properties by acting on the pump pulse shape. PMID- 20588422 TI - Formation of filament and plasma channel by the Bessel incident beam in Ar gas: role of the outer part of the beam. AB - We theoretically investigate the formation of filament and plasma channel in Ar gas by intense femtosecond pulses in the Bessel, truncated Bessel, and combination of two Gaussian modes. Through the numerical results obtained by solving the generalized nonlinear Schrodinger equation coupled with the electron density evolution equation, we find that there is a radial energy flow during the propagation, which implies that the outer part of the Bessel beam serves as an energy reservoir for the filament formed around the central peak. The results we obtain for the Bessel and truncated Bessel incident beams are consistent in that we can obtain a longer filament and plasma channel if more energy is reserved in the outer part of the Bessel incident beam. More interestingly we show that the combined use of two Gaussian beams with different beam diameters increases the energy stored in the outer part of the beam, and as a result the lengths of the filament and plasma channel become remarkably longer. This can be a practical choice to improve the propagation properties. PMID- 20588423 TI - Characterization of long-haul 112Gbit/s PDM-QAM-16 transmission with and without digital nonlinearity compensation. AB - In this paper long-haul, single channel, polarization multiplexed 16-state quadrature amplitude modulation (PDM-QAM-16) transmission at 112 Gbit/s is investigated. Novel digital signal processing techniques are used to perform carrier phase estimation and symbol estimation, in combination with nonlinear digital backpropagation. The results obtained demonstrate that the use of digital nonlinear backpropagation increases the optimum launch power from -4 dBm to -1 dBm with a consequent increase in maximum reach from 1440 km to 2400 km, which is a record transmission distance for QAM-16 reported to date for an SMF link with EDFAs only. Furthermore, experimental measurements are supported by simulations, based on the link used in the experiment. PMID- 20588424 TI - Pulse-contrast degradation due to pump phase-modulation in optical parametric chirped-pulse amplification system. AB - We theoretically study the pulse-contrast degradation of optical parametric chirped pulse amplification (OPCPA) system pumped by a temporally phase-modulated laser. We reveal two physical mechanisms that reduce the contrast in such a parametric process: the effect of phase transfer caused by group-velocity mismatch (GVM) and the effect of FM-to-AM conversion caused by group-velocity dispersion (GVD). Degradation of the contrast is quantified via numerical simulations. To reduce the effect of phase transfer, a pair of OPCPAs seeded by the signal and idler respectively, is studied for effectively improving the contrast in such a case with pump phase modulation. The results presented in this paper are of particular importance for extremely intense laser applications requiring high contrast. PMID- 20588425 TI - Small-angle scattering computed tomography (SAS-CT) using a Talbot-Lau interferometerand a rotating anode x-ray tube:theory and experiments. AB - X-ray differential phase contrast imaging methods, including projection imaging and the corresponding computed tomography (CT), have been implemented using a Talbot interferometer and either a synchrotron beam line or a low brilliance x ray source generated by a stationary-anode x-ray tube. From small-angle scattering events which occur as an x-ray propagates through a medium, a signal intensity loss can be recorded and analyzed for an understanding of the micro structures in an image object. This has been demonstrated using a Talbot-Lau interferometer and a stationary-anode x-ray tube. In this paper, theoretical principles and an experimental implementation of the corresponding CT imaging method are presented. First, a line integral is derived from analyzing the cross section of the small-angle scattering events. This method is referred to as small angle scattering computed tomography (SAS-CT). Next, a Talbot-Lau interferometer and a rotating-anode x-ray tube were used to implement SAS-CT. A physical phantom and human breast tissue sample were used to demonstrate the reconstructed SAS-CT image volumes. PMID- 20588426 TI - Propagation characteristics of hybrid modes supported by metal-low-high index waveguides and bends. AB - Hybrid-mode waveguides consisting of a metal surface separated from a high index medium by a low index spacer have attracted much interest recently. Power is concentrated in the low index spacer region for this waveguide. Here we investigate the properties of the hybrid mode in detail and numerically demonstrate the possibility of realizing compact waveguide bends using this wave guiding scheme. PMID- 20588427 TI - Large-area organic distributed feedback laser fabricated by nanoreplica molding and horizontal dipping. AB - The fabrication of visible wavelength vertically emitting distributed feedback (DFB) lasers with a subwavelength grating fabricated by a replica molding process and an active polymer layer printed by a horizontal dipping process is reported. The combined techniques enable the organic DFB laser to be uniformly fabricated over large surface areas upon a flexible plastic substrate, with an approach that is compatible with roll-based manufacturing. Using a fixed grating period and depth, DFB laser output wavelength is controlled over a 35 nm range through manipulation of the waveguide layer thickness, which is controlled by the speed of the horizontal dipping process. We also demonstrate that the active area of the structure may be photolithographically patterned to create dense arrays of discrete DFB lasers. PMID- 20588428 TI - Image processing guided analysis for estimation of bacteria colonies number by means of optical transforms. AB - A novel method for evaluation of bacterial colonies number (Colony Forming Units- CFU), is described. Proposed algorithm, based on the Mellin transform, allows the CFU evaluation, invariant for the spatial orientation and scale changes. The proposed method involves image recording of bacteria grown in Petri dishes, calculation of the Fourier spectrum followed by coordinates transformation, and determination of the Mellin transform. It was proved that there is a high correlation between CFU and maxima of Mellin spectra. The method was practically implemented for evaluation of antibacterial activity of silver-based nanomaterials and the effect of an additional laser light irradiation. PMID- 20588429 TI - Characterizing ultrabroadband attosecond lasers. AB - Recent progress in sub-laser-cycle gating of high-order harmonic generation promises to push the limits on optical pulse durations below the atomic unit of time, 24 as, which corresponds to a bandwidth broader than 75 eV. However, the available techniques for attosecond pulse measurement are valid only for narrow bandwidth spectra, due to one of the key approximations made in the phase retrieval. Here we report a new technique for characterizing attosecond pulses, whereby the spectral phase of the attosecond pulse is extracted from the oscillation component with the dressing laser frequency in the photoelectron spectrogram. This technique, termed PROOF (Phase Retrieval by Omega Oscillation Filtering), can be applied to characterizing attosecond pulses with ultrabroad bandwidths. PMID- 20588430 TI - Delivery of picosecond lasers in multimode fibers for coherent anti-Stokes Raman scattering imaging. AB - We investigated the possibility of using standard commercial multimode fibers (MMF), Corning SMF28 fibers, to deliver picosecond excitation lasers for coherent anti-Stokes Raman scattering (CARS) imaging. We theoretically and/or experimentally analyzed issues associated with the fiber delivery, such as dispersion length, walk-off length, nonlinear length, average threshold power for self-phase modulations, and four-wave mixing (FWM). These analyses can also be applied to other types of fibers. We found that FWM signals are generated in MMF, but they can be filtered out using a long-pass filter for CARS imaging. Finally, we demonstrated that MMF can be used for delivery of picosecond excitation lasers in the CARS imaging system without any degradation of image quality. PMID- 20588431 TI - High speed optical quantum random number generation. AB - We present a fully integrated, ready-for-use quantum random number generator (QRNG) whose stochastic model is based on the randomness of detecting single photons in attenuated light. We show that often annoying deadtime effects associated with photomultiplier tubes (PMT) can be utilized to avoid postprocessing for bias or correlations. The random numbers directly delivered to a PC, generated at a rate of up to 50 Mbit/s, clearly pass all tests relevant for (physical) random number generators. PMID- 20588432 TI - Isotropic nonmagnetic flat cloaks degenerated from homogeneous anisotropic trapeziform cloaks. AB - We propose a novel kind of trapeziform cloak requiring only homogeneous anisotropic materials. Large-scale flat cloaks can be degenerated from the general trapeziform cloak with PEC inner boundary, and be realized by isotropic nonmagnetic materials for optical frequencies with controlled index profiles and improved invisibility. With the support of PEC inner boundary, large vehicles and objects of arbitrary shape can be concealed between the PEC and ground, and PEC can be firm by adding pillars in the cloaking space. Full-wave simulations validate the proposed cloaking concept, which is not only based on simple isotropic nonmagnetic materials but also realizable in practice. PMID- 20588433 TI - Asymmetric planar terahertz metamaterials. AB - We report an experimental observation of three distinct resonances in split ring resonators (SRRs) for both vertical and horizontal electric field polarizations at normal incidence by use of terahertz time-domain spectroscopy. Breaking the symmetry in SRRs by gradually displacing the capacitive gap from the centre towards the corner of the ring allows for an 85% modulation of the fundamental inductive-capacitive resonance. Increasing asymmetry leads to the evolution of an otherwise inaccessible high quality factor electric quadrupole resonance that can be exploited for bio-sensing applications in the terahertz region. PMID- 20588434 TI - Autonomous tip/tilt alignment and phasing of a distributed aperture imaging testbed. AB - Star-9 is an experimental demonstration of distributed aperture imaging built at the Lockheed Martin Advanced Technology Center. White light from a scene generator enters an array of nine actively controlled telescopes, and is combined at a focused image plane. This paper describes the algorithms used to automatically bring each telescope's relative tip/tilt and phasing errors to within the operational range of the control system. The algorithms work with point-sources as well as with extended scenes. Experimental results and software algorithms are presented. PMID- 20588435 TI - Enhancement of quality factor for TE whispering-gallery modes in microcylinder resonators. AB - The enhancement of quality factor for TE whispering-gallery modes is analyzed for three-dimensional microcylinder resonators based on the destructive interference between vertical leakage modes. In the microcylinder resonator, the TE whispering gallery modes can couple with vertical propagation modes, which results in vertical radiation loss and low quality factors. However, the vertical loss can be canceled by choosing appropriate thickness of the upper cladding layer or radius of the microcylinder. A mode quality factor increase by three orders of magnitude is predicted by finite-difference time-domain simulation. Furthermore, the condition of vertical leakage cancellation is analyzed. PMID- 20588436 TI - Design of highly transparent glasses with broadband antireflective subwavelength structures. AB - We present a design optimization of highly transparent glasses with broadband antireflective subwavelength structures (SWS) based on the theoretical calculation using a rigorous coupled wave analysis method. It is found that optical transmission characteristics of SWS integrated glasses are governed mainly by the zero-order condition considering multiple internal reflections but not external reflection. By utilizing parabola-shaped SWS on both sides of the glasses with a period of 200 nm and a height of 200 nm, an average transmittance of 99.58% is achieved over a whole range of visible wavelength. Transmission band shrinkage effects of the SWS integrated glass are also observed with increasing the incident angle of light. PMID- 20588437 TI - In-series double cladding fibers for simultaneous refractive index and temperature measurement. AB - A fiber-optic sensor for simultaneous measurement of refractive index (RI) and temperature was proposed and demonstrated. It was fabricated by cascading two sections of specialty double cladding (DC) fibers which presented a pair of well separated resonant spectra dips. The sensing properties of temperature and ambient RI were investigated theoretically based on the coupled mode theory. Experimental results indicated that these two resonant spectra shifts were linearly dependent on the variation of the RI in the range of 1.3333 approximately 1.4118 and on the temperature in the range of -10 degrees C approximately + 80 degrees C. Such a fiber-optic sensor is simple and easy for mass production and has potential applications for biosensors or chemical sensors. PMID- 20588438 TI - Self-collimating photonic crystal antireflection structure for both TE and TM polarizations. AB - We present a high-efficiency antireflection structure for both TE and TM polarizations in two-dimensional self-collimating square lattice photonic crystal consisting of air holes in silicon. The design parameters of the optimal antireflection structure can be obtained by using the concept of Fresnel coefficients and the finite-difference time-domain simulations. The photonic crystal operating in almost identical self-collimation frequencies for two polarizations exhibits a large reflection coefficient for TE and a very small one for TM polarization. In this case, the antireflection structure for TE can also improve the transmission for TM polarization. To confirm a highly efficient antireflection structure designed, we investigate the transmission data of three finite photonic crystal samples consisting of 36, 38 and 40 unit cells for the cases without and with the antireflection structures through finite-difference time-domain simulations. PMID- 20588439 TI - Suppression of parasitic oscillations in a core-doped ceramic Nd:YAG laser by Sm:YAG cladding. AB - The onset of parasitic oscillations limits the extraction efficiency and therefore energy scaling of Q-switched lasers. A solid-state laser was end pumped with a fiber-coupled diode laser and operated in q-cw as well as in passively Q switched operation. For Q-switched operation, we demonstrate the suppression of parasitic oscillations in a core-doped ceramic Nd:YAG laser by Sm:YAG cladding. PMID- 20588441 TI - Efficient generation of highly squeezed light with periodically poled MgO:LiNbO3. AB - We report on efficient generation of continuous-wave squeezed light and second harmonics with a periodically poled MgO:LiNbO(3) (PPMgLN) crystal which enables us to utilize the large nonlinear optical coefficient d(33). We achieved the squeezing level of -7.60+/-0.15 dB at 860 nm by utilizing a subthreshold optical parametric oscillator with a PPMgLN crystal. We also generated 400 mW of second harmonics at 430 nm from 570 mW of fundamental waves with 70% of conversion efficiency by using a PPMgLN crystal inside an external cavity. PMID- 20588440 TI - In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models. AB - Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal. PMID- 20588442 TI - On femtosecond micromachining of HPHT single-crystal diamond with direct laser writing using tight focusing. AB - We investigate the formation of diversiform micro-/nano-structures in High Pressure High-Temperature (HPHT) synthetic single-crystal diamond by tight focusing 200 fs regeneratively amplified Ti: Sapphire laser pulses centered at lambda = 800 nm. Ablated samples of synthetic single crystal nanodiamond and their acetate replicas are analyzed using scanning electron microscopy (SEM). Using pulse energies that are significantly above the threshold for permanent change, it is shown from this work that amplified femtosecond pulses are capable of producing controlled modification of HPHT single-crystal diamond at size scales below the diffraction limit and provided negligible collateral heating and shock-wave damage. This is attributed to the low thermal losses and negligible hydrodynamic expansion of the ablated material during the femtosecond laser pulse. It is shown that low pulse energy is a key factor for the accurate and precise machining of micropattems. PMID- 20588443 TI - Zeeman laser scanning confocal microscope and its ability on reduction of specimen-induced spherical aberration. AB - The spherical aberration induced by refractive-index mismatch results in the degradation on the quality of sectioning images in conventional confocal laser scanning microscope (CLSM). In this research, we have derived the theory of image formation in a Zeeman laser scanning confocal microscope (ZLSCM) and conducted experiments in order to verify the ability of reducing spherical aberration in ZLSCM. A Zeeman laser is used as the light source and produces the linearly polarized photon-pairs (LPPP) laser beam. With the features of common-path propagation of LPPP and optical heterodyne detection, ZLSCM shows the ability of reducing the specimen-induced spherical aberration and improving the axial resolution simultaneously. PMID- 20588444 TI - Reconstruction of fluorescence/bioluminescence sources in biological medium with spatial filter. AB - We propose a new method for reconstruction of emitting source distributions by use of a spatial filter and a successive updating process of the forward model for fluorescence/bioluminescence diffuse optical tomography. The spatial filter transforms a set of the measurement data to a single source strength at a position of interest, and the forward model is updated by use of the estimated source strengths. This updating process ignores the dispensable source positions from reconstruction according to the reconstructed source distribution, and the spatial resolution of the reconstructed image is improved. The estimated sources are also used for the reduction of artifacts induced by noises based on the singular value decomposition. Some numerical experiments show the advantages of the proposed method by comparing the present results with those obtained by the conventional methods of the least squares method nd Algebraic Reconstruction Technique. Finally the criteria for practical use of the method are quantitatively presented by the simulations for 2D and 3D geometries. PMID- 20588445 TI - Broadband coupler between silicon waveguide and hybrid plasmonic waveguide. AB - Efficient broadband coupling of light between a dielectric waveguide and a hybrid plasmonic waveguide is investigated theoretically. A plasmonic linear taper is used as a coupler which connects the two types of waveguides. Broadband coupling is realized by such a compact plasmonic taper with a length of only 0.4 microm, which achieves a coupling efficiency of 70% (1.5 dB) at the 1.55 microm telecommunication wavelength. PMID- 20588446 TI - Simultaneous observation of superluminal and slow light propagation in a nested fiber ring resonator. AB - We observe both superluminal and slow light propagation simultaneously in a nested fiber ring resonator. The two outputs of the resonator exhibit different absorption characteristics that produce opposite dispersion performance. The transmission spectra of two outputs are demonstrated experimentally for a variety of coupler settings. In particular, the group delays of the resonator for various values of the coupling coefficients are demonstrated theoretically and experimentally. We also discuss potential applications of the resonator. PMID- 20588447 TI - Flat and low dispersion in highly nonlinear slot waveguides. AB - We propose highly nonlinear slot waveguides with flat and low dispersion over a wide wavelength range. Si nano-crystal and chalcogenide glass are considered as slot materials. Over a 244-nm bandwidth, dispersion of 0+/-0.16 ps/(nmxm) is achieved in a silicon nano-crystal slot waveguide, with a nonlinear coefficient of 2874 /(Wm). The As(2)S(3) slot waveguide exhibits dispersion of 0+/-0.17 ps/(nmxm) over a bandwidth of 249 nm, with a nonlinear coefficient 16 times larger than that of As(2)S(3) rib waveguides and a nonlinear figure of merit three times larger than that of Si strip waveguides. PMID- 20588448 TI - Monolithic all-glass pump combiner scheme for high-power fiber laser systems. AB - We report on an integrated all-glass pump combiner for ytterbium-doped high power fiber lasers. The combining of multiple pump fibers with an active double clad fiber for high power amplification was successfully achieved by splicing them to a dichromatically coated planar convex lens. The measured coupling efficiency of such a combining scheme was typically in excess of 80%, with 86.5% achieved in maximum. Theoretical analysis is discussed in order to get optimized parameters and to consider the scaling of this type of coupler to higher average powers. PMID- 20588449 TI - Practical tests for distinguishing slow light from saturable absorption. AB - A series of practical tests of slow light (light with reduced group velocity) in saturable absorbers is proposed. These include experimental tests for saturable absorption, which can mimic slow light effects in saturable media, the dependence of slow light on the mutual coherence of pump and probe, since both slow and fast light effects can be simulated with incoherent sources, and the influence of polarization. The principal requirements for practical observation of spectral hole burning are reviewed and shown to be achievable for a wide range of saturable media with the narrow line sources now available. PMID- 20588450 TI - Ultrafast laser inscription of a high-gain Er-doped bismuthate glass waveguide amplifier. AB - An Er-doped bismuthate glass waveguide amplifier has been fabricated using ultrafast laser inscription. Under zero pump conditions, the 87.0 mm long waveguide exhibited a fiber-to-fiber insertion loss of 4.0 dB at 1618 nm, outside the Er(3+) ion absorption band. We attribute approximately 1.8 dB of the insertion loss to coupling losses, 0.2 dB to Fresnel reflections and approximately 2.0 dB to propagation losses. When pumped using 1050 mW of 980 nm light, the amplifier exhibited a peak internal gain per unit length of 2.3 dB.cm( 1) at 1533 nm and a peak fiber-to-fiber net gain of 16.0 dB at 1533 nm. In this paper we also report the results of output power saturation and noise figure measurements. PMID- 20588451 TI - Coupled defects in one-dimensional photonic crystal films fabricated with glancing angle deposition. AB - This work presents the successful fabrication of 1D photonic crystals (PCs) with two defects using the glancing angle deposition (GLAD) technique. We study the coupling behavior of the two PC defects and demonstrate the ability to control the defect interaction. GLAD allows engineering of film nanostructure to produce PCs with sinusoidal refractive index variation through control of film nanostructure and porosity. Two phase-shift defects are introduced into the refractive index profile of the film. The observed defect-defect coupling is explained by a coupled-oscillator model and the interaction strength is found to decrease exponentially with increasing defect separation. Furthermore, the results demonstrate the promise of GLAD as a platform technology for PC research and device fabrication. PMID- 20588452 TI - Fiber optic long period grating sensors with a nanoassembled mesoporous film of SiO2 nanoparticles. AB - A novel approach to chemical application of long period grating (LPG) optical fibers was demonstrated, which were modified with a film nanoassembled by the alternate deposition of SiO(2) nanoparticles (SiO(2) NPs) and poly(diallyldimethyl ammonium chloride) (PDDA). Nanopores of the sensor film could be used for sensitive adsorption of chemical species in water, which induced the changes in the refractive index (RI) of the light propagating in the cladding mode of the optical fiber, with a concomitant effect on the transmission spectrum in the LPG region. The prepared fiber sensor was highly sensitive to the change in the RI of the surrounding medium and the response time was very fast within 10 s. In addition, chemical infusion into the film was tested using a porphyrin compound, tetrakis-(4-sulfophenyl)porphine (TSPP), which could be saturated within a few min. The lowest detectable concentration of the TSPP analyte was 10 microM. The TSPP infusion led to the development of well pronounced dual resonance bands, indicating a large increase in the optical thickness of the film. The RI of the film was dramatically increased from 1.200 to ca. 1.540. PMID- 20588453 TI - In-situ determination of astro-comb calibrator lines to better than 10 cm s(-1). AB - Improved wavelength calibrators for high-resolution astrophysical spectrographs will be essential for precision radial velocity (RV) detection of Earth-like exoplanets and direct observation of cosmological deceleration. The astro-comb is a combination of an octave-spanning femtosecond laser frequency comb and a Fabry Perot cavity used to achieve calibrator line spacings that can be resolved by an astrophysical spectrograph. Systematic spectral shifts associated with the cavity can be 0.1-1 MHz, corresponding to RV errors of 10-100 cm/s, due to the dispersive properties of the cavity mirrors over broad spectral widths. Although these systematic shifts are very stable, their correction is crucial to high accuracy astrophysical spectroscopy. Here, we demonstrate an in-situ technique to determine the systematic shifts of astro-comb lines due to finite Fabry-Perot cavity dispersion. The technique is practical for implementation at a telescope based spectrograph to enable wavelength calibration accuracy better than 10 cm/s. PMID- 20588454 TI - Long distance transmission in few-mode fibers. AB - Using multimode fibers for long-haul transmission is proposed and demonstrated experimentally. In particular few-mode fibers (FMFs) are demonstrated as a good compromise since they are sufficiently resistant to mode coupling compared to standard multimode fibers but they still can have large core diameters compared to single-mode fibers. As a result these fibers can have significantly less nonlinearity and at the same time they can have the same performance as single mode fibers in terms of dispersion and loss. In the absence of mode coupling it is possible to use these fibers in the single-mode operation where all the data is carried in only one of the spatial modes throughout the fiber. It is shown experimentally that the single-mode operation is achieved simply by splicing single-mode fibers to both ends of a 35-km-long dual-mode fiber at 1310 nm. After 35 km of transmission, no modal dispersion or excess loss was observed. Finally the same fiber is placed in a recirculating loop and 3 WDM channels each carrying 6 Gb/s BPSK data were transmitted through 1050 km of the few-mode fiber without modal dispersion. PMID- 20588455 TI - Design and analysis of metal/multi-insulator/metal waveguide plasmonic Bragg grating. AB - A metal/multi-insulator/metal waveguide plasmonic Bragg grating with a large dynamic range of index modulation is investigated analytically and numerically. Theoretical formalism of the dispersion relation for the present and general one dimensional gratings is developed for TMwaves in the vicinity of each stop band.Wide-band and narrow-band designs with their respective FWHM bandwidths of 173.4 nm and < 3.4 nm in the 1550 nm band using a grating length of <16.0 microm are numerically demonstrated. Time-average power vortexes near the silica-silicon interfaces are revealed in the stop band and are attributed to the contra-flow interaction and simultaneous satisfactions of the Bragg condition for the incident and backward-diffracted waves. An enhanced forward-propagating power is thus shown to occur over certain sections within one period due to the power coupling from the backward-diffracted waves. PMID- 20588456 TI - Selective imaging of nano-particle contrast agents by a single-shot x-ray diffraction technique. AB - Iron oxide nano-particles have very different x-ray diffraction properties from tissue. They can be clearly visualized against suppressed tissue background in a single-shot x-ray diffraction imaging technique. This technique is able to acquire both diffraction and absorption images from a single grating-modulated projection image through analysis in the spatial frequency domain. We describe the use of two orthogonal transmission gratings to selectively retain diffraction signal from iron oxide particles that are larger than a threshold size, while eliminating the background signal from soft tissue and bone. This approach should help the tracking of functionalized particles in cell labeling and targeted therapy. PMID- 20588457 TI - Modal effects on pump-pulse propagation in an Ar-filled capillary. AB - Accurate three-dimensional modelling of nonlinear pulse propagation within a gas filled capillary is essential for understanding and improving the XUV yield in high harmonic generation. We introduce both a new model based on a multimode generalized nonlinear Schrodinger equation and a novel spatio-spectral measurement technique to which the model can be compared. The theory shows excellent agreement with the measured output spectrum and the spatio-spectral measurement reveals that the model correctly predicts higher order mode contributions to spectral broadening of the pulse. Fluorescence from the excited argon is used to verify the predicted ion distribution along the capillary. PMID- 20588458 TI - Two-step method for lens system design. AB - This paper proposes a method for lens system design. It consists of two main steps called Glass-Selection Step and Further-Optimization Step. We modify coordinate-wise algorithm to obtain the glass combination in Glass-Selection Step. In Further-Optimization Step, we use modified coordinate-wise algorithm combined with modified evolutionary algorithm to find out the optimal solution. We succeed in obtaining high quality design with the proposed method. PMID- 20588459 TI - Emission polarization control in semiconductor quantum dots coupled to a photonic crystal microcavity. AB - We study the optical emission of single semiconductor quantum dots weakly coupled to a photonic-crystal micro-cavity. The linearly polarized emission of a selected quantum dot changes continuously its polarization angle, from nearly perpendicular to the cavity mode polarization at large detuning, to parallel at zero detuning, and reversing sign for negative detuning. The linear polarization rotation is qualitatively interpreted in terms of the detuning dependent mixing of the quantum dot and cavity states. The present result is relevant to achieve continuous control of the linear polarization in single photon emitters. PMID- 20588460 TI - Circuit modeling of the transmissivity of stacked two-dimensional metallic meshes. AB - This paper presents a simple analytical circuit-like model to study the transmission of electromagnetic waves through stacked two-dimensional (2-D) conducting meshes. When possible the application of this methodology is very convenient since it provides a straightforward rationale to understand the physical mechanisms behind measured and computed transmission spectra of complex geometries. Also, the disposal of closed-form expressions for the circuit parameters makes the computation effort required by this approach almost negligible. The model is tested by proper comparison with previously obtained numerical and experimental results. The experimental results are explained in terms of the behavior of a finite number of strongly coupled Fabry-Perot resonators. The number of transmission peaks within a transmission band is equal to the number of resonators. The approximate resonance frequencies of the first and last transmission peaks are obtained from the analysis of an infinite structure of periodically stacked resonators, along with the analytical expressions for the lower and upper limits of the pass-band based on the circuit model. PMID- 20588461 TI - Tunable millimeter-wave frequency synthesis up to 100 GHz by dual-wavelength Brillouin fiber laser. AB - We demonstrate the generation of microwave and millimeter-wave frequencies from 26 to 100 GHz by heterodyning the output modes of a dual-wavelength fiber laser based on stimulated Brillouin scattering. The output frequency is tunable in steps of 10.3 MHz, equal to the free spectral range of the resonator. The noise properties of the beat frequency indicate a microwave linewidth of <2 Hz. We discuss potential for operation into the terahertz regime. PMID- 20588462 TI - Single-pass sum-frequency-generation of 589-nm yellow light based on dual wavelength Nd:YAG laser with periodically-poled LiTaO(3) crystal. AB - We demonstrate a compact all-solid-state yellow laser source based on Q-switched dual-wavelength Nd:YAG laser and periodically-poled LiTaO(3) crystal. 589-nm yellow light was generated by single-pass sum-frequency generation of the fundamental IR waves at 1064 and 1319 nm. The maximum output power of yellow light was 506 mW and the corresponding conversion efficiency was approximately 5.5% [W(-1)cm(-1)]. PMID- 20588463 TI - Analytical model for optical bistability in nonlinear metal nano-antennae involving Kerr materials. AB - Optical bistability at nanoscale is a promising way to realize optical switching, a key component of integrated nanophotonic devices. In this work we present an analytical model for optical bistability in a metal nano-antenna involving Kerr nonlinear medium based on detailed analysis of the correlation between the incident and extinction light intensity under surface plasmon resonance (SPR). The model allows one to construct a clear picture on how the threshold, contrast, and other characteristics of optical bistability are influenced by the nonlinear coefficient, incident light intensity, local field enhancement factor, SPR peak width, and other physical parameters of the nano-antenna. It shows that the key towards low threshold power and high contrast optical bistability in the nanosystem is to reduce the SPR peak width. This can be achieved by reducing the absorption of metal materials or introducing gain media into nanosystems. PMID- 20588464 TI - Analysis of throughput for multilayer infrared meanderline waveplates. AB - A meanderline wave retarder is a unique type of frequency-selective-surface (FSS) that enables a change in the state of optical polarization. The principles of operation are very similar to a typical crystalline waveplate, such that the artificially structured meanderline array has both 'slow' and 'fast' axes that provide a phase offset between two orthogonal wave components. In this paper, we study the behavior and response of multilayered meanderline quarter-wave retarders designed for operation at 10.6 mum wavelength (28.28 THz). It will be shown that meanderline quarter-wave plates with more than a single layer exhibit improved transmission throughput at infrared frequencies due to impedance matching, similar to a multilayer optical film coating. Numerical data, both from simulations and measurements, are presented to validate this claim. PMID- 20588465 TI - Two-dimensional amorphous photonic structure in the ligament of bivalve Lutraria maximum. AB - Here we report a two-dimensional amorphous photonic structure (2D APS) discovered in the ligament of bivalve Lutraria maximum, based on scanning electron microscopy and fiber optic spectrometry combined with the image processing technology and pair correlation function analysis. This structure contains 70% in volume of parallel aragonite fibers embedded in a protein matrix. These fibers, in cross section, are hexagonal to polygonal with diameters of 194nm and are packed in short-range order with a nearest-neighbor distance of 202nm. Moreover, experimentally measured reflectance spectrum and theoretical predictions prove that this photonic structure gives rise to a golden structural color with the peak wavelength at about 650nm. We expect this unraveled structure may inspire the design and synthesis of a novel 2D APS. PMID- 20588466 TI - High-density channel alignment of graded index core polymer optical waveguide and its crosstalk analysis with ray tracing method. AB - We fabricate graded index (GI) multi-channel polymer optical waveguides comprised of poly methyl methacrylate (PMMA)-poly benzyl methacrylate copolymer for the purpose of achieving high thermal stability in the GI profiles. The waveguides obtained show slightly higher propagation loss (0.033 dB/cm at 850 nm) than doped PMMA based GI-core polymer waveguides we have reported, due to the excess scattering loss inherent to the mixture of copolymer and homo-polymer in the core area. In this paper, we focus on the influence of the excess scattering loss on mode conversion and inter-channel crosstalk. We simulate the behavior of light propagating inside the core with and without the scattering effect. Using the simulation, the excess loss experimentally observed in the copolymer-core waveguide is successfully reproduced, and then, we find that the excess scattering loss of 0.008 dB/cm could increase the inter-channel crosstalk from 30 dB to -23 dB which agrees with the experimentally observed value. Although the simulation of the inter-channel crosstalk was performed only on our GI-core polymer optical waveguides, it is capable of modeling the conventional SI rectangular-core waveguides. Some amount of excess scattering is generally observed in the conventional SI-core waveguides, and thus, the application of this simulation to SI-core waveguides allows a feasible design for high-density alignment of the waveguides. PMID- 20588467 TI - Experimental signatures of dispersive waves emitted during soliton collisions. AB - We report experimental evidence of dispersive waves with enhanced redshift generated through soliton collisions in a photonic crystal fiber with two zero dispersion wavelengths. Experiments are performed to study both controlled collisions under twin-pulse excitation, as well as spontaneous collisions arising from noise-induced supercontinuum generation. Experimental results for the spectral and statistical properties are in good agreement with numerical simulations and are shown to be associated with extreme-value like distributions with long tails. PMID- 20588468 TI - Dark pulse quantum dot diode laser. AB - We describe an operating regime for passively mode-locked quantum dot diode laser where the output consists of a train of dark pulses, i.e., intensity dips on a continuous background. We show that a dark pulse train is a solution to the master equation for mode-locked lasers. Using simulations, we study stability of the dark pulses and show they are consistent with the experimental results. PMID- 20588469 TI - Plasmonic electromagnetically-induced transparency in symmetric structures. AB - A broken symmetry is generally believed to be a prerequisite for plasmonic electromagnetically-induced transparency (EIT), since the asymmetry allows the excitation of the otherwise forbidden dark mode. Nevertheless, according to the picture of magnetic plasmon resonance (MPR)-mediated plasmonic EIT, we show that plasmonic EIT can be achieved even in symmetric structures based on the second order MPR. This not only sharpens our understanding of the existing concept, but also provides a profound insight into the plasmonic coherent interference in the near-field zone. PMID- 20588470 TI - Infrared imaging of an A549 cultured cell by a vibrational sum-frequency generation detected infrared super-resolution microscope. AB - We performed infrared (IR) spectroscopic imaging of molecular species in cultured cell interiors of A549 cells using in-house developed vibrational sum-frequency generation detected IR super-resolution microscope. The spatial resolution of this IR microscope was approximately 1.1 microm, which exceeds the diffraction limit of IR light. Therefore, we clearly observed differences in the signal intensity at various IR wavelengths which appear to originate from the differing IR absorptions of specific vibrational modes, and reveal the distribution of molecular species in the single cell. These results were never imaged with the conventional IR microscope. PMID- 20588471 TI - Symmetry breaking and strong coupling in planar optical metamaterials. AB - We demonstrate narrow transmission resonances at near-infrared wavelengths utilizing coupled asymmetric split-ring resonators (SRRs). By breaking the symmetry of the coupled SRR system, one can excite dark (subradiant) resonant modes that are not readily accessible to symmetric SRR structures. We also show that the quality factor of metamaterial resonant elements can be controlled by tailoring the degree of asymmetry. Changing the distance between asymmetric resonators changes the coupling strength and results in resonant frequency tuning due to resonance hybridization. PMID- 20588472 TI - Novel elastic scattering model for the understanding of the Anomalous transmittance for Au nanoparticle layer. AB - The optical transmission spectra of several samples of gold nanoparticle layers were examined using a modified Drude model proposed with a novel elastic scattering parameter, gamma'. Although the measured transmission spectra deviated from the simple calculation from Mie scattering, it was explained well by the modified model assuming elastic and inelastic scattering in the form of the collision frequency of free electrons within a metal particle due to the particle boundary. The particle-size and inter-particle-distance dependences of gamma' were extracted within the framework of the proposed model from the curve of best fit of the transmittance spectra. PMID- 20588473 TI - Highly tunable optical activity in planar achiral terahertz metamaterials. AB - Using terahertz time domain spectroscopy we demonstrate tunable polarization rotation and circular dichroism in intrinsically non-chiral planar terahertz metamaterials without twofold rotational symmetry. The observed effect is due to extrinsic chirality arising from the mutual orientation of the metamaterial plane and the propagation direction of the incident terahertz wave. PMID- 20588474 TI - Algorithm and experiment of whole-aperture wavefront reconstruction from annular subaperture Hartmann-Shack gradient data. AB - A new method is proposed for testing a rotationally symmetric aspheric surface with several annular subapertures based on a Hartmann-Shack sensor. In consideration of the limited sampling of Hartmann-Shack subapertures in the matching annular subaperture, a new algorithm for whole-aperture wavefront reconstruction from annular subaperture Hartmann-Shack gradient data is established. The algorithm separates the tip, tilt, and defocus misalignments for each annular subaperture by introducing annular Zernike polynomials. The performance of the algorithm is evaluated for different annular subaperture configurations, and the sensitivity of the algorithm to the detector error of the wavefront gradient is analyzed. The algorithm is verified by the experimental results. PMID- 20588475 TI - Polarization insensitive resonance-domain blazed binary gratings. AB - Three variants of binary blazed gratings with subwavelength features are considered, which have high first-order efficiencies in the non-paraxial domain for arbitrarily polarized light. A combination of effective medium theory and further parametric optimization with the Fourier modal method are used in design. Experimental demonstration is provided by electron beam lithography on a structure etched in a Si3N4 layer on top of a SiO2 substrate, with period approximately 3.5lambda at lambda = 633 nm. The measured efficiency (81% for TE and 85% for TM polarization) agrees well with the calculated value, 84%. PMID- 20588476 TI - Continuous adaptive beam pointing and tracking for laser power transmission. AB - The adaptive beam pointing concept has been revisited for the purpose of controlled transmission of laser energy from an optical transmitter to a target. After illumination, a bidirectional link is established by a retro-reflector on the target and an amplifier-phase conjugate mirror (A-PCM) on the transmitter. By setting the retro-reflector's aperture smaller than the diffraction limited spot size but big enough to provide sufficient amount of optical feedback, a stable link can be maintained and light that hits the retro-reflector's surrounded area can simultaneously be reconverted into usable electric energy. The phase conjugate feedback ensures that amplifier's distortions are compensated and the target tracked accurately.After deriving basic arithmetic expressions for the proposed system, a section is devoted for the motivation of free-space laser power transmission which is supposed to find varied applicability in space. As an example, power transmission from a satellite to the earth is described where recently proposed solar power generating structures on high-altitudes receive the power above the clouds to provide constant energy supply.In the experimental part, an A-PCM setup with reflectivity of about R(A-PCM) = 100 was realized using a semiconductor optical amplifier and a photorefractive self-pumped PCM. Simulation results show that a reflectivity of R(A-PCM)>1000 could be obtained by improving the self-pumped PCM's efficiency. That would lead to a transmission efficiency of eta>90%. PMID- 20588477 TI - Evaluating and identifying pearls and their nuclei by using optical coherence tomography. AB - Optical coherence tomography (OCT) has been utilized to evaluate pearls including their nuclei noninvasively. By visualizing the internal structure of a pearl, we could measure the thickness of its nacre layer, observe the fine sub-structure of the nacre, and inspect the nucleus through the nacre. The system also allowed us to classify pearls into beaded- and non-beaded ones; usually, the saltwater ones have nuclei even though there are beaded freshwater pears and non-beaded saltwater pearls. Any cracks, crevices, or blemishes not only in the nacre but in the nucleus of a pearl could be clearly visualized. The OCT system was based on a 20 kHz swept-source of a 1.31microm central wavelength and an 110 nm full-width at-half-maximum (FWHM) bandwidth. To get the 2-D images all around the circumference of a pearl, the pearl was rotated by a motorized rotating stage. And to achieve 3-D volume images, galvano-scans were made along two axes. Of all things, the OCT allowed us to check the use of a forbidden nucleus, usually made of a Giant Clam shell thus fragile, without hurting the pearl. With this modality, we believe, it would be possible evaluating pearls both in qualitative and quantitative. Comparison with the images taken with an optical microscope and X-ray radiograph gives the refractive index of pearl as about 1.53 in average. PMID- 20588478 TI - Assessment of the use of a diffuser in propagation-based x-ray phase contrast imaging. AB - A rotating random-phase-screen diffuser is sometimes employed on synchrotron x ray imaging beamlines to ameliorate field-of-view inhomogeneities due to electron beam instabilities and beamline optics phase artifacts. The ideal result is a broader, more uniformly illuminated beam intensity for cleaner coherent x-ray images. The spinning diffuser may be modeled as an ensemble of transversely random thin phase screens, with the resulting set of intensity maps over the detector plane being incoherently averaged over the ensemble. Whilst the coherence width associated with the source is unaffected by the diffuser, the magnitude of the complex degree of second-order coherence may be significantly reduced [K. S. Morgan, S. C. Irvine, Y. Suzuki, K. Uesugi, A. Takeuchi, D. M. Paganin, and K. K. W. Siu, Opt. Commun. 283, 216 (2010)]. Through use of a computational model and experimental data obtained on x-ray beamline BL20XU at SPring-8, Japan, we investigate the effects of such a diffuser on the quality of Fresnel diffraction fringes in propagation-based x-ray phase contrast imaging. We show that careful choice of diffuser characteristics such as thickness and fiber size, together with appropriate placement of the diffuser, can result in the ideal scenario of negligible reduction in fringe contrast whilst the desired diffusing properties are retained. PMID- 20588479 TI - Sub-15 nm beam confinement by two crossed x-ray waveguides. AB - We have combined two high transmission planar x-ray waveguides glued onto each other in a crossed geometry to form an effective quasi-point source. From measurements of the far-field diffraction pattern, the phase and amplitude of the near-field distribution is retrieved using the error-reduction algorithm. In agreement with finite difference field simulations (forward calculation), the reconstructed exit wave intensity distribution (inverse calculation) exhibits a full width at half maximum (FWHM) below 15 nm in both dimensions. Finally, holographic imaging is successfully demonstrated for the crossed waveguide device by translation of a lithographic test structure through the waveguide beam. PMID- 20588480 TI - Pattern compensation in SOA-based gates. AB - We propose a novel scheme employing complementary data inputs to overcome the patterning normally associated with semiconductor optical amplifier based gates and demonstrate the scheme experimentally at 42.6Gb/s. The scheme not only avoids introducing patterning during switching, but also compensates for much of the patterning present on the input data. A novel gate was developed for the experiment to provide the complementary signals required for the scheme. PMID- 20588481 TI - Multi-channel silicon photonic receiver based on ring-resonators. AB - We demonstrated a high performance monolithically integrated multi-channel receiver fabricated on the SOI platform. This receiver is composed of a 1 x 8 Si based ring-resonators filter and an array of high speed waveguided Ge-on-Si photodetectors. The optical channel spacing is about 1.5 nm. The responsivity of Ge-on-Si photodetector is about 1.0 A/W at the wavelength range of 1554 nm to 1564 nm. Each channel is capable of operating at a data rate of 20 Gbps, resulting in an aggregate data rate of 160 Gbps. At a BER of 1 x 10(-11), the receiver showed an optical input sensitivity of between -20 dBm and -21 dBm for each channel at 10 Gbps data rate. PMID- 20588482 TI - Applicability of an EM-CCD for spatially resolved TIR-ICS. AB - In this work we systematically explored performance of an EM-CCD as a detector for spatially resolved total internal reflection image correlation spectroscopy (TIR-ICS) with respect to adjustable parameters. We show that variations in the observation volume (pixel binning) can be well described by a simple structural term omega. To test the sensitivity of camera-based TIR-ICS we measured diffusion coefficients and particle numbers (PN) of fluorescent probes of different sizes (Fluorospheres, GFP and labeled antibodies) at varying viscosities, concentrations, and sampling rates. TIR-ICS allowed distinguishing between different probe concentrations with differences in PN of 5% and differences of 6% in D by acquiring only 15 independent measurement runs. PMID- 20588483 TI - Optical time division multiplexer on silicon chip. AB - In this work, we experimentally demonstrate a novel broadband optical time division multiplexer (OTDM) on a silicon chip. The fabricated devices generate 20 Gb/s and 40 Gb/s signals starting from a 5 Gb/s input signal. The proposed design has a small footprint of 1mm x 1mm. The system is inherently broadband with a bandwidth of over 100nm making it suitable for high-speed optical networks on chip. PMID- 20588484 TI - Quantitative phase retrieval of a complex-valued object using variable function orders in the fractional Fourier domain. AB - We propose a novel and effective method to quantitatively recover a complex valued object from diffraction intensity maps recorded in the fractional Fourier domain. A wavefront modulation is introduced in the wave path, and several diffraction intensity maps are recorded through variable function orders in the fractional Fourier transform. A new phase retrieval algorithm is then proposed, and advantages of the proposed algorithm are also discussed. A proof-of-principle study is presented to show the feasibility and effectiveness of the proposed method. PMID- 20588485 TI - 1.54 microm electroluminescence from p-Si anode organic light emitting diode with Bphen: Er(DBM)(3)phen as emitter and Bphen as electron transport material. AB - 1.54 microm Si-anode organic light emitting devices with Er(DBM)(3)phen: Bphen and Bphen/Bphen:Cs(2)CO(3) as the emissive and electron transport layers (the devices are referred to as the Bphen-based devices) have been investigated. In comparison with the AlQ-based devices with the same structure but with AlQ:Er(DBM)(3)Phen and AlQ as the emissive and electron transport layers, the maximum EL intensity and maximum power efficiency from the Bphen-based devices increase by a factor of 3 and 2.2, respectively. The optimized p-Si anode resistivity of the Bphen-based device of 10 Omega.cm is significantly lower than that of the AlQ-based device. The NIR EL improvement can be attributed to the energy transfer from Bphen to the Er complex and equilibrium of electron injection from the Sm/Au cathode and hole injection from the p-Si anode at a higher level. PMID- 20588486 TI - Coherent combination of high power fiber amplifiers in a two-dimensional re imaging waveguide. AB - Four actively phase-locked beams produced by fiber amplifiers in a master oscillator power amplifier (MOPA) configuration were coherently combined in a glass capillary re-imaging waveguide producing more than 100 W of coherent output with 80% combining efficiency and excellent beam quality. The beam combiner components maintained a temperature below 30 degrees C with no external cooling at >100 W of combined power. PMID- 20588487 TI - Single-resonance optical pumping spectroscopy and application in dressed-state measurement with atomic vapor cell at room temperature. AB - By monitoring the transmission of probe laser beam (also served as coupling laser beam) which is locked to a cycling hyperfine transition of cesium D(2) line, while pumping laser is scanned across cesium D(1) or D(2) lines, the single resonance optical pumping (SROP) spectra are obtained with atomic vapor cell. The SROP spectra indicate the variation of the zero-velocity atoms population of one hyperfine fold of ground state, which is optically pumped into another hyperfine fold of ground state by pumping laser. With the virtue of Doppler-free linewidth, high signal-to-noise ratio (SNR), flat background and elimination of crossover resonance lines (CRLs), the SROP spectra with atomic vapor cell around room temperature can be employed to measure dressed-state splitting of ground state, which is normally detected with laser-cooled atomic sample only, even if the dressed-state splitting is much smaller than the Doppler-broaden linewidth at room temperature. PMID- 20588488 TI - Strategies for three-dimensional particle tracking with holographic video microscopy. AB - The video stream captured by an in-line holographic microscope can be analyzed on a frame-by-frame basis to track individual colloidal particles' three-dimensional motions with nanometer resolution. In this work, we compare the performance of two complementary analysis techniques, one based on fitting to the exact Lorenz Mie theory and the other based on phenomenological interpretation of the scattered light field reconstructed with Rayleigh-Sommerfeld back-propagation. Although Lorenz-Mie tracking provides more information and is inherently more precise, Rayleigh-Sommerfeld reconstruction is faster and more general. The two techniques agree quantitatively on colloidal spheres' in-plane positions. Their systematic differences in axial tracking can be explained in terms of the illuminated objects' light scattering properties. PMID- 20588489 TI - InGaAs/GaAs saturable absorber for diode-pumped passively Q-switched dual wavelength Tm:YAP lasers. AB - We demonstrate the first use of InGaAs/GaAs as a saturable absorber in the Q switching of a diode pumped Tm(3+) doped laser operating at the wavelengths of 1940 nm and 1986 nm. The influence of the semiconductor saturable absorber's (SESA) position and thermal lens effect on the Q-switch characteristics was investigated. With a pump power of 35 W, the maximum pulse energy of 28.1 microJ with a pulse width of 447 ns at the pulse repetition frequency (PRF) of 43.7 kHz was obtained by selecting the appropriate position of the SESA. PMID- 20588490 TI - Plasmonic nanofocusing using a metal-coated axicon prism. AB - We propose an excitation method for the localization of photons at the apex of a metal coated axicon prism. The cone angle of the prism and the metallic film thickness are designed to match the excitation conditions for surface plasmons. The plasmons propagate along the sides of the prism and converge at its apex. The resulting nanofocusing was investigated by simulating the intensity distributions around the apex of the prism using a finite-difference time-domain algorithm. For incident radial polarization, a localized and field enhanced spot is generated by the constructive interference of surface plasmons. PMID- 20588491 TI - High efficient loading of two atoms into a microscopic optical trap by dynamically reshaping the trap with a spatial light modulator. AB - We demonstrated trapping two neutral (87)Rb atoms in a two site optical ring lattice generated by reflecting a single laser beam from a computer controlled spatial light modulator directly. The ring lattice was transformed into a Gaussian trap by dynamically displaying the holograms animation movie on the modulator. The trapped atoms follow the evolution of traps and move into the same microscopic dipole trap at the end. The detected success rate of this manipulation is larger than 90%. Under imposing the near resonance light, we observed strong light-induce collision between two atoms. PMID- 20588492 TI - High efficiency cholesteric liquid crystal lasers with an external stable resonator. AB - An amplified cholesteric liquid crystal (CLC) laser performance is demonstrated by utilizing a binary-dye mixture (with 62 wt% DCM and 38 wt% PM597) as the active medium and an external stable resonator. The measured results show that the laser efficiency is enhanced as compared to the highest efficiency of each individual dye. Furthermore, using such an active CLC in an external stable resonator leads to a approximately 92X improved efficiency over the single CLC laser. In this instance, the binary-dye doped CLC simultaneously functions as laser oscillator and amplifier. PMID- 20588493 TI - Cascadable and reconfigurable photonic logic gates based on linear lightwave interference and non-linear phase erasure. AB - Feasibility of cascading and reconfiguring a pair of linear-nonlinear all-optical logic gate structures is experimentally demonstrated using RF photonics. Progress in highly integrated O/E/O repeaters over Si/InP hybrid platforms enables large scale reconfigurable gate arrays. PMID- 20588494 TI - Magnetic imaging at linearly polarized x-ray sources. AB - We present a method for high-resolution magnetic imaging at linearly polarized partially coherent x-ray sources. The magnetic imaging was realized via Fourier transform holography. In order to achieve elliptical x-ray polarization, three different filters were designed based on the x-ray magnetic circular dichroism effect. We present proof-of-principle images of magnetic nanostructures and discuss the application of the method for future experiments at free-electron laser sources. PMID- 20588495 TI - Dynamics of actively mode-locked Quantum Cascade Lasers. AB - The impact of upper state lifetime and spatial hole burning on pulse shape and stability in actively mode locked QCLs is investigated by numerical simulations. It is shown that an extended upper state lifetime is necessary to achieve stable isolated pulse formation per roundtrip. Spatial hole burning helps to reduce the pulse duration by supporting broadband multimode lasing, but introduces pulse instabilities which eventually lead to strongly structured pulse shapes that further degrade with increased pumping. At high pumping levels gain saturation and recovery between pulses leads to suppression of mode locking. In the absence of spatial hole burning the laser approaches single-mode lasing, while in the presence of spatial hole burning the mode locking becomes unstable and the laser dynamics does not reach a steady state anymore. PMID- 20588496 TI - Improved sensitivity for two-photon frequency-domain lifetime measurement. AB - We demonstrate a method to improve the measurement sensitivity of two-photon frequency-domain lifetime measurements in poor signal to background conditions. This technique uses sinusoidal modulation of the two-photon excitation source and detection of the second harmonic of the modulation frequency that appears in the emission. Additionally, we present the mathematical model which describes how the observed phase shift and amplitude demodulation factor of two-photon phosphorescence emission are related to the phosphorescence lifetime and modulation frequency. We demonstrate the validity of the model by showing the existence of new frequency terms in the phosphorescence emission generated from the quadratic nature of two-photon absorption and by showing that the phase shift and demodulation match theory for all frequency components. PMID- 20588497 TI - Analysis on volume grating induced by femtosecond laser pulses. AB - We report on a kind of self-assembled volume grating in silica glass induced by tightly focused femtosecond laser pulses. The formation of the volume grating is attributed to the multiple microexplosion in the transparent materials induced by the femtosecond pulses. The first order diffractive efficiency is in dependence on the energy of the pulses and the scanning velocity of the laser greatly, and reaches as high as 30%. The diffraction pattern of the fabricated grating is numerically simulated and analyzed by a two dimensional FDTD method and the Fresnel Diffraction Integral. The numerical results proved our prediction on the formation of the volume grating, which agrees well with our experiment results. PMID- 20588498 TI - Random lasing action of randomly assembled ZnO nanowires with MgO coating. AB - Lasing characteristics of randomly assembled ZnO nanowires (NWs) coated with different thickness of MgO layers are investigated. It is found that the MgO coated randomly assembled ZnO NWs demonstrate random lasing action and the formation of coherent optical feedback is dependent on the thickness of MgO coating. Pump threshold of the MgO coated randomly assembled ZnO NWs increases with the increase of MgO thickness. Nevertheless, the appropriate use of MgO coating can reduce the pump threshold by approximately 30% and the corresponding characteristic temperature can be improved by 28 K. PMID- 20588499 TI - Two-dimensional optical phased array antenna on silicon-on-insulator. AB - Optical wireless links can offer a very large bandwidth and can act as a complementary technology to radiofrequency links. Optical components nowadays are however rather bulky. Therefore, we have investigated the potential of silicon photonics to fabricated integrated components for wireless optical communication. This paper presents a two-dimensional phased array antenna consisting of grating couplers that couple light off-chip. Wavelength steering of $0.24 degrees /nm is presented reducing the need of active phase modulators. The needed steering range is $1.5 degrees . The 3dB angular coverage range of these antennas is about $0.007pi sr with a directivity of more than 38dBi and antenna losses smaller than 3dB. PMID- 20588500 TI - Optimizing the fluorescent yield in two-photon laser scanning microscopy with dispersion compensation. AB - A challenge for nonlinear imaging in living tissue is to maximize the total fluorescent yield from each fluorophore. We investigated the emission rates of three fluorophores-rhodamine B, a red fluorescent protein, and CdSe quantum dots while manipulating the phase of the laser excitation pulse at the focus. In all cases a transform-limited pulse maximized the total yield to insure the highest signal-to-noise ratio. Further, we find evidence of fluorescence antibleaching in quantum dot samples. PMID- 20588501 TI - Resonantly diode-pumped continuous-wave and Q-switched Er:YAG laser at 1645 nm. AB - We describe an efficient Er:YAG laser that is resonantly pumped using continuous wave (CW) laser diodes at 1470 nm. For CW lasing, it emits 6.1 W at 1645 nm with a slope efficiency of 36%, the highest efficiency reported for an Er:YAG laser that is pumped in this manner. In Q-switched operation, the laser produces diffraction-limited pulses with an average power of 2.5 W at 2 kHz PRF. To our knowledge this is the first Q-switched Er:YAG laser resonantly pumped by CW laser diodes. PMID- 20588502 TI - Acceleration of FDTD mode solver by high-performance computing techniques. AB - A two-dimensional (2D) compact finite-difference time-domain (FDTD) mode solver is developed based on wave equation formalism in combination with the matrix pencil method (MPM). The method is validated for calculation of both real guided and complex leaky modes of typical optical waveguides against the bench-mark finite-difference (FD) eigen mode solver. By taking advantage of the inherent parallel nature of the FDTD algorithm, the mode solver is implemented on graphics processing units (GPUs) using the compute unified device architecture (CUDA). It is demonstrated that the high-performance computing technique leads to significant acceleration of the FDTD mode solver with more than 30 times improvement in computational efficiency in comparison with the conventional FDTD mode solver running on CPU of a standard desktop computer. The computational efficiency of the accelerated FDTD method is in the same order of magnitude of the standard finite-difference eigen mode solver and yet require much less memory (e.g., less than 10%). Therefore, the new method may serve as an efficient, accurate and robust tool for mode calculation of optical waveguides even when the conventional eigen value mode solvers are no longer applicable due to memory limitation. PMID- 20588503 TI - Terahertz waves emitted from an optical fiber. AB - We report a simple method of creating terahertz waves by applying the photo Dember effect in a (100)-oriented InAs film coated onto the 45-degree wedged-end facet of an optical fiber. The terahertz waves are generated by infrared pulses guided through the optical fiber which is nearly in contact with a sample and then measured by a conventional photo-conductive antenna detector. Using this alignment-free terahertz source, we performed proof-of-principle experiments of terahertz time-domain spectroscopy and near-field terahertz microscopy. We obtained a bandwidth of 2 THz and 180-microm spatial resolution. Using this method, the THz imaging resolution is expected to be reduced to the size of the optical fiber core. Applications of this device can be extended to sub-wavelength terahertz spectroscopic imaging, miniaturized terahertz system design, and remote sensing. PMID- 20588504 TI - Spectroscopic and laser properties of Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal at 1.5-1.6 microm. AB - An Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal doped with 24.1 at.% Yb(3+) and 1.1 at.% Er(3+) ions was grown by the flux method. The polarized spectroscopic properties related to the operation of 1.5-1.6 microm laser of the crystal were evaluated at room temperature. The laser properties of a 0.7-mm-thick, c-cut crystal were investigated in diode-end-pumped hemispherical and plano-plano cavities, respectively. Compared with those of Er(3+):Yb(3+):YAl(3)(BO(3))(4) crystal obtained under similar experimental conditions, higher maximum output peak power, higher slope efficiency, and lower threshold were achieved in the Er(3+):Yb(3+):LuAl(3)(BO(3))(4) crystal. PMID- 20588505 TI - Stimulated Raman scattering microscope with shot noise limited sensitivity using subharmonically synchronized laser pulses. AB - We propose and demonstrate the use of subharmonically synchronized laser pulses for low-noise lock-in detection in stimulated Raman scattering (SRS) microscopy. In the experiment, Yb-fiber laser pulses at a repetition rate of 38 MHz are successfully synchronized to Ti:sapphire laser pulses at a repetition rate of 76 MHz with a jitter of <8 fs by a two-photon detector and an intra-cavity electro optic modulator. By using these pulses, high-frequency lock-in detection of SRS signal is accomplished without high-speed optical modulation. The noise level of the lock-in signal is found to be higher than the shot noise limit only by 1.6 dB. We also demonstrate high-contrast, 3D imaging of unlabeled living cells. PMID- 20588506 TI - A compact Acousto-Optic Lens for 2D and 3D femtosecond based 2-photon microscopy. AB - We describe a high speed 3D Acousto-Optic Lens Microscope (AOLM) for femtosecond 2-photon imaging. By optimizing the design of the 4 AO Deflectors (AODs) and by deriving new control algorithms, we have developed a compact spherical AOL with a low temporal dispersion that enables 2-photon imaging at 10-fold lower power than previously reported. We show that the AOLM can perform high speed 2D raster-scan imaging (>150 Hz) without scan rate dependent astigmatism. It can deflect and focus a laser beam in a 3D random access sequence at 30 kHz and has an extended focusing range (>137 mum; 40X 0.8NA objective). These features are likely to make the AOLM a useful tool for studying fast physiological processes distributed in 3D space. PMID- 20588507 TI - Proportional enlargement of movement by using an optically driven multi-link system with an elastic joint. AB - Diverse movements using optical manipulation have been introduced. These are generally performed in the focal region of the laser beam. To achieve a wider range of movements based on precise motion transformation, an effective method for optical manipulation that overcomes the important obstacles such as small optical trapping forces, friction, and the viscosity of fluids is required. A multi-link system with an elastic joint is introduced that provides precise motion transformation and amplification. By considering the physical properties of the structure and the optical trapping force, an elastic micron-scale joint with the simple shape of a thin plate was designed. As a further example of a multi-link system with an elastic joint, a double 4-link system for motion enlargement was designed and fabricated. By performing experimental evaluations of the fabricated structures, it was confirmed that multi-link systems with an elastic joint were effective tools for precise motion transformation through optical manipulation. PMID- 20588508 TI - Liquid filled microstructured optical fiber for x-ray detection. AB - A liquid filled microstructured optical fiber (MOF) is used to detect x-rays. Numerical analysis and experimental observation leads to geometric fiber optics theory for MOF photon transmission. A model using this theory relates the quantity and energy of absorbed x-ray photons to transmitted MOF generated photons. Experimental measurements of MOF photon quantities compared with calculated values show good qualitative agreement. The difference between the calculated and measured values is discussed. PMID- 20588509 TI - A simple and reliable method to determine LP(11) cutoff wavelength of bend insensitive fiber. AB - We present a simple and reliable method based on the spectral splice loss measurement to determine the cutoff wavelength of bend insensitive fiber. PMID- 20588510 TI - Known plaintext attack on double random phase encoding using fingerprint as key and a method for avoiding the attack. AB - We have shown that the application of double random phase encoding (DRPE) to biometrics enables the use of biometrics as cipher keys for binary data encryption. However, DRPE is reported to be vulnerable to known-plaintext attacks (KPAs) using a phase recovery algorithm. In this study, we investigated the vulnerability of DRPE using fingerprints as cipher keys to the KPAs. By means of computational experiments, we estimated the encryption key and restored the fingerprint image using the estimated key. Further, we propose a method for avoiding the KPA on the DRPE that employs the phase retrieval algorithm. The proposed method makes the amplitude component of the encrypted image constant in order to prevent the amplitude component of the encrypted image from being used as a clue for phase retrieval. Computational experiments showed that the proposed method not only avoids revealing the cipher key and the fingerprint but also serves as a sufficiently accurate verification system. PMID- 20588511 TI - Real-time coherence holography. AB - Coherence holography capable of real-time recording and reconstruction is proposed and experimentally demonstrated with a generic Leith-type coherence hologram. The coherence hologram is optically generated in real-time using a Mach Zehnder interferometer and reconstructed using a Sagnac radial shearing interferometer. With this method one can create an optical field distribution with a desired spatial coherence function, and visualize the coherence function in real-time as the contrast and phase variations in an interference fringe pattern. The reconstructed image of the complex coherence function has been quantified with the Fourier transform method of fringe-pattern analysis. PMID- 20588512 TI - Investigation of the electronic and physical properties of defect structures responsible for laser-induced damage in DKDP crystals. AB - Laser-induced damage at near operational laser excitation conditions can limit the performance of potassium dihydrogen phosphate (KH(2)PO(4), or KDP) and its deuterated analog (DKDP) which are currently the only nonlinear optical materials suitable for use in large-aperture laser systems. This process has been attributed to pre-existing damage precursors that were incorporated or formed during growth that have not yet been identified. In this work, we present a novel experimental approach to probe the electronic structure of the damage precursors. The results are modeled assuming a multi-level electronic structure that includes a bottleneck for 532 nm excitation. This model reproduces our experimental observations as well as other well-documented behaviors of laser damage in KDP crystals. Comparison of the electronic structure of known defects in KDP with this model allows for identification of a specific class that we postulate may be the constituent defects in the damage precursors. The experimental results also provide evidence regarding the physical parameters affecting the ability of individual damage precursors to initiate damage, such as their size and defect density; these parameters were found to vary significantly between KDP materials that exhibit different damage performance characteristics. PMID- 20588513 TI - Silicon photonic dynamic optical channel leveler with external feedback loop. AB - We demonstrate a dynamic optical channel leveler composed of a variable optical attenuator (VOA) integrated monolithically with a defect-mediated photodiode in a silicon photonic waveguide device. An external feedback loop mimics an analog circuit such that the photodiode directly controls the VOA to provide blind channel leveling within +/-1 dB across a 7-10 dB dynamic range for wavelengths from 1530 nm to 1570 nm. The device consumes approximately 50 mW electrical power and occupies a 6 mm x 0.1 mm footprint per channel. Dynamic leveling is accomplished without tapping optical power from the output path to the photodiode and thus the loss penalty is minimized. PMID- 20588514 TI - Spectral characterization of porous dielectric subwavelength THz fibers fabricated using a microstructured molding technique. AB - We report two novel fabrication techniques, as well as THz spectral transmission and propagation loss measurements of subwavelength plastic wires with highly porous (up to 86%) and non-porous transverse geometries. The two fabrication techniques we describe are based on the microstructured molding approach. In one technique the mold is made completely from silica by stacking and fusing silica capillaries to the bottom of a silica ampoule. The melted material is then poured into the silica mold to cast the microstructured preform. Another approach uses a microstructured mold made of a sacrificial plastic which is co-drawn with a cast preform. Material from the sacrificial mold is then dissolved after fi ber drawing. We also describe a novel THz-TDS setup with an easily adjustable optical path length, designed to perform cutback measurements using THz fibers of up to 50 cm in length. We fi nd that while both porous and non-porous subwavelength fibers of the same outside diameter have low propagation losses (alpha Yb(3+) energy transfer in 0.8CaSiO(3)-0.2Ca(3)(PO(4))(2) eutectic glass. AB - In this work we report the study of energy transfer between Nd(3+) and Yb(3+) ions in glasses with the 0.8CaSiO(3)-0.2Ca(3)(PO(4))(2) eutectic composition at room temperature by using steady-state and time-resolved laser spectroscopy. The Nd(3+)?Yb(3+) transfer efficiency obtained from the Nd(3+) lifetimes in the single doped and codoped samples reaches 73% for the highest Nd(3+) concentration. The donor decay curves obtained under pulsed excitation have been used to establish the multipolar nature of the Nd(3+)-->Yb(3+) transfer process and the energy transfer microparameter. The nonradiative energy transfer is consistent with an electric dipole-dipole interaction mechanism assisted by energy migration among donors. Back transfer from Yb(3+) to Nd(3+) is also observed. PMID- 20588518 TI - Robust and fast computation for the polynomials of optics. AB - Mathematical methods that are poorly known in the field of optics are adapted and shown to have striking significance. Orthogonal polynomials are common tools in physics and optics, but problems are encountered when they are used to higher orders. Applications to arbitrarily high orders are shown to be enabled by remarkably simple and robust algorithms that are derived from well known recurrence relations. Such methods are demonstrated for a couple of familiar optical applications where, just as in other areas, there is a clear trend to higher orders. PMID- 20588519 TI - Observation of transparency of Erbium-doped silicon nitride in photonic crystal nanobeam cavities. AB - One dimensional nanobeam photonic crystal cavities are fabricated in an Er-doped amorphous silicon nitride layer. Photoluminescence from the cavities around 1.54 microm is studied at cryogenic and room temperatures at different optical pump powers. The resonators demonstrate Purcell enhanced absorption and emission rates, also confirmed by time resolved measurements. Resonances exhibit linewidth narrowing with pump power, signifying absorption bleaching and the onset of stimulated emission in the material at both 5.5 K and room temperature. We estimate from the cavity linewidths that Er has been pumped to transparency at the cavity resonance wavelength. PMID- 20588520 TI - Size-related third-order optical nonlinearities of Au nanoparticle arrays. AB - We report a systematic study of the size-related nonlinear optical properties of triangular Au particles. The triangular Au nanoparticle arrays of four sizes (37 nm, 70 nm, 140 nm and 190 nm) were fabricated on quartz substrates using nanosphere lithography. By performing the Z-scan method with femtosecond laser (800 nm, 50 fs), the optical nonlinearities of Au nanoparticle arrays were determined. The results showed a size-related competition between two mechanisms of groundstate bleaching and two-photon absorption. As the size increased, the nonlinear absorption changed from two-photon absorption to saturated absorption, while the nonlinear refraction changed from self-defocusing to self-focusing. These size-tunable nonlinearities make it possible to optimize the one- and two photon figures of merit, W and T, for all-optical switching. PMID- 20588521 TI - Experimental demonstration of a flexible and stable semiconductor laser linewidth emulator. AB - We propose and demonstrate experimentally a laser source whose linewidth is adjustable independently of its other characteristics. This source can be used to test whether a particular laser would be suitable in a system, without the need to purchase several different lasers. It also has the advantage that the linewidth is generated digitally so it is extremely stable over time. We demonstrate a dialed-linewidth emulator between 256 kHz to 150 MHz. The narrowest linewidth shown by this technique is the original linewidth of the semiconductor laser source used in the setup. We also investigate the effect of driving our modulator into its nonlinear range. PMID- 20588522 TI - Optical properties of metal-dielectric-metal microcavities in the THz frequency range. AB - We present an experimental and theoretical study of the optical properties of metal-dielectric-metal structures with patterned top metallic surfaces, in the THz frequency range. When the thickness of the dielectric slab is very small with respect to the wavelength, these structures are able to support strongly localized electromagnetic modes, concentrated in the subwavelength metal-metal regions. We provide a detailed analysis of the physical mechanisms which give rise to these photonic modes. Furthermore, our model quantitatively predicts the resonance positions and their coupling to free space photons. We demonstrate that these structures provide an efficient and controllable way to convert the energy of far field propagating waves into near field energy. PMID- 20588523 TI - PMD tolerance of 288 Gbit/s Coherent WDM and transmission over unrepeatered 124 km of field-installed single mode optical fiber. AB - Low-cost, high-capacity optical transmission systems are required for metropolitan area networks. Direct-detected multi-carrier systems are attractive candidates, but polarization mode dispersion (PMD) is one of the major impairments that limits their performance. In this paper, we report the first experimental analysis of the PMD tolerance of a 288Gbit/s NRZ-OOK Coherent Wavelength Division Multiplexing system. The results show that this impairment is determined primarily by the subcarrier baud rate. We confirm the robustness of the system to PMD by demonstrating error-free performance over an unrepeatered 124km field-installed single-mode fiber with a negligible penalty of 0.3dB compared to the back-to-back measurements. PMID- 20588524 TI - Exact error rate analysis of equal gain and selection diversity for coherent free space optical systems on strong turbulence channels. AB - Exact error rate performances are studied for coherent free-space optical communication systems under strong turbulence with diversity reception. Equal gain and selection diversity are considered as practical schemes to mitigate turbulence. The exact bit-error rate for binary phase-shift keying and outage probability are developed for equal gain diversity. Analytical expressions are obtained for the bit-error rate of differential phase-shift keying and asynchronous frequency-shift keying, as well as for outage probability using selection diversity. Furthermore, we provide the closed-form expressions of diversity order and coding gain with both diversity receptions. The analytical results are verified by computer simulations and are suitable for rapid error rates calculation. PMID- 20588525 TI - 84 dB amplification, 0.46 J in a 10 Hz output diode-pumped Nd:YLF ring amplifier with phase-conjugated wavefront corrector. AB - A diode-pumped joule class in a 10 Hz output Nd:YLF ring amplifier has been developed. A phase conjugate plate was developed as a wavefront corrector for the residual wavefront distortion of an Nd:YLF rod. We have demonstrated a 0.46 J output of 10 ns pulse duration at 10 Hz repetition rate with 1.5 nJ of input energy. The effective gain of the ring amplifier system was 84.8 dB. To our knowledge, this is the highest magnification with joule-level output energy in a single-stage amplifier system that has ever been built. As a preamplifier system, this system contributed a demonstration of 21.3 J in a 10 Hz output diode-pumped Nd:glass zigzag slab laser system with a stimulated Brillouin scattering- phase conjugation mirror. We describe a robust and effective method of wavefront correction for high-energy laser systems. PMID- 20588526 TI - In vivo investigation of human cone photoreceptors with SLO/OCT in combination with 3D motion correction on a cellular level. AB - We present a further improvement of our SLO/OCT imaging system which enables to practically eliminate all eye motion artifacts with a correction accuracy approaching sub-cellular dimensions. Axial eye tracking is achieved by using a hardware based, high speed tracking system that consists of a rapid scanning optical delay line in the reference arm of the interferometer. A software based algorithm is employed to correct for transverse eye motion in a post-processing step. The instrument operates at a frame rate of 40 en-face fps with a field of view of approximately 1 degrees x 1 degrees. Dynamic focusing enables the recording of 3D volumes of the human retina with cellular resolution throughout the entire imaging depth. Several volumes are stitched together to increase the total field of view. Different features of the three dimensional structure of cone photoreceptors are investigated in detail and at different eccentricities from the fovea. PMID- 20588527 TI - Room-temperature electroluminescence from Si microdisks with Ge quantum dots. AB - A current-injected silicon-based light-emitting device was fabricated on silicon on-insulator (SOI) by embedding Ge self-assembled quantum dots into a silicon microdisk resonator with p-i-n junction for current-injection. Room-temperature resonant electroluminescence (EL) from Ge self-assembled quantum dots in the microdisk was successfully observed under current injection, and observed EL peaks corresponding to the whispering gallery modes (WGMs) supported by the microdisk resonator were well identified by means of numerical simulations. PMID- 20588528 TI - Intracavity parametric generation of nanosecond terahertz radiation using quasi phase-matching. AB - We report the use of quasi-phase-matching techniques based on periodically-poled MgO:LiNbO(3) for the generation of nanosecond duration pulses of terahertz radiation in intracavity optical parametric oscillators. Multiple idler-waves are generated with temporal studies indicating that the initiating process is the expected parametric down-conversion, but followed by cascaded difference frequency generation. A number of grating geometries have been explored, revealing the presence of dual solutions for the quasi-phase-matching process in the general case. Choice of grating parameters so as to minimize oscillation threshold while simultaneously ensuring effective extraction of the THz radiation is considered. PMID- 20588529 TI - Full-range polarization-sensitive swept-source optical coherence tomography by simultaneous transversal and spectral modulation. AB - Polarization-sensitive swept-source optical coherence tomography (PS-SS-OCT) is used to measure three-dimensional phase-retardation images of birefringent biological tissue in vivo. PS-SS-OCT with continuous source polarization modulation is used to multiplex the incident states of polarization in the signal frequency of each A-scan. Although it offers the advantage of measurement speed that is as high as that of standard SS-OCT, its disadvantage is low axial measurement range. To overcome this drawback, we employed the B-M-mode scan (BM scan) method, which removes complex conjugate ambiguity by applying phase modulation along the transversal scanning direction. Since polarization modulation and BM-scan are applied in different scanning directions, these methods can be combined to make the optimum use of both full range and polarization-sensitive imaging. Phase fluctuations that cause measurement failure were numerically canceled before demodulating the B-scan oriented modulation. After removing complex conjugate artifacts, the axial measurement range was 5.35 mm, and the signal-to-conjugate ratio was 40.5 dB. We demonstrated retinal imaging using the PS-SS-OCT system with a frequency-swept laser at a center wavelength of 1064 nm and an axial resolution of 11.4 microm in tissue. Full range polarization-sensitive retinal images showed characteristic birefringence of fibrous tissues such as retinal nerve fiber, sclera, and lamina cribrosa. PMID- 20588530 TI - Optical lens with electrically variable focus using an optically hidden dielectric structure. AB - Electrically variable gradient index liquid crystal lens is developed that uses flat uniform liquid crystal layer and electrodes. The spatial modulation of the electric field across the lens aperture is obtained by the modulation of the effective dielectric constant of an integrated doublet lens structure. The dielectric constants of two materials, composing the doublet, are chosen to be different at electrical driving frequencies, while their optical refractive indexes are the same, hiding thus the structure from the optical point of view. This "hidden layer" approach decouples the electrical and optical functions of that structure, increases significantly the performance of the lens and enables new functionalities. The technical performance and various driving schemes of the obtained lens are presented and analyzed. PMID- 20588531 TI - Power and energy scaling of a diode-end-pumped Nd:YLF laser through gain optimization. AB - An end-pumped Nd:YLF laser was demonstrated, which delivered 60.3 W continuous wave and more than 52 W Q-switched average power for all repetition rates from 5 to 30 kHz. To achieve this, an analytical solution to estimate and optimize the unsaturated gain in an end-pumped laser gain medium was derived. The approach presented here should open up the route for scaling end-pumped lasers to even higher power and energy levels. PMID- 20588532 TI - Plasmonic nanograting tip design for high power throughput near-field scanning aperture probe. AB - We design nanogratings consisting of concentric plasmonic resonance grooves on the metallic sidewalls of near-field scanning probe aperture to increase the power throughput without losing the imaging resolution. Nanograting tip design involves choosing the proper pitch length and the cut location of grooves. Four different nanograting designs are evaluated, as compared with standard single aperture pyramidal near-field scanning probe without grating patterns. We show that, by adding nano-grooves at the location of electromagnetic field intensity maximum along interface and with the pitch period matching the surface plasmon wavelength, the power throughput can be greatly increased by at least a factor of 530 at 405nm UV wavelength with 100nm diameter aperture probe. PMID- 20588533 TI - 360-degree viewable image-plane disk-type multiplex holography by one-step recording. AB - By tilting both the input and the image planes of a holographic system and adopting a diverging reference wave for hologram recording, a special type of multiplex hologram can be produced in one-step. Due to symmetry of reconstruction geometry, the reconstructed 3D image from this type of rainbow hologram can be viewed by the surrounding observers simultaneously. Theoretical formulation for the holographic process is presented. Some numerical simulation and experimental result demonstrating the characteristics of the reconstructed image are included. PMID- 20588534 TI - A PbS quantum dots fiber amplifier excited by evanescent wave. AB - A PbS quantum dots (QDs) fiber amplifier was fabricated and characterized by using a standard single mode fiber (SMF) coupler. The fiber amplifier was fabricated by coating PbS QDs doped sol-gel films onto the tapered SMF coupler. Through the evanescent wave, the PbS quantum dots were excited. With a 980 nm wavelength laser diode (LD) as the pump, the fiber amplifier exhibited a wide band optical gain at 1310 nm with the largest gain as high as 10 dB. The amplified spontaneous emission (ASE) noise is very low resulted from the amplifier configuration of evanescent wave exciting, which is critical to improve the signal-to-noise ratio. Therefore the proposed fiber amplifier will find great potential in the fiber-optic communication systems. PMID- 20588535 TI - Stress induced birefringence in hybrid TIR/PBG guiding solid photonic crystal fibers. AB - We report on two types of polarization maintaining solid photonic crystal fibers that guide light by a combination of a photonic bandgap and total internal reflection. Group and phase birefringence are studied experimentally and numerically for stress-applying parts made from B-doped and F-doped silica. The stress field originating from Ge-doped cladding rods is shown to interfere with the stress field from the B-doped and F-doped rods. Since the differential expansion coefficients of B-doped and F-doped silica have opposite signs this interference is either destructive or constructive. Consequently, we found that the fiber with F-doped stress applying parts has the highest modal phase birefringence, and polarization cross talk is characterized by an h-parameter below 310(-5) m(-1). PMID- 20588536 TI - Influence of strain and pressure to the effective refractive index of the fundamental mode of hollow-core photonic bandgap fibers. AB - We investigate the phase sensitivity of the fundamental mode of hollow-core photonic bandgap fibers to strain and acoustic pressure. A theoretical model is constructed to analyze the effect of axial strain and acoustic pressure on the effective refractive index of the fundamental mode. Simulation shows that, for the commercial HC-1550-02 fiber, the contribution of mode-index variation to the overall phase sensitivities to axial strain and acoustic pressure are respectively approximately -2% and approximately -17%. The calculated normalized phase-sensitivities of the HC-1550-02 fiber to strain and acoustic pressure are respectively 1 epsilon(-1) and -331.6 dB re microPa(-1) without considering mode index variation, and 0.9797 epsilon(-1) and -333.1 dB re microPa(-1) when mode index variation is included in the calculation. The latter matches better with the experimentally measured results. PMID- 20588537 TI - High transmission and low color cross-talk plasmonic color filters using triangular-lattice hole arrays in aluminum films. AB - Three primary color (red, green and blue) filters consisting of subwavelength triangular-lattice hole arrays in an aluminum film on glass were simulated and fabricated. A silicon dioxide cap layer, deposited on the patterned aluminum film, was found to almost double the transmission efficiency for all the filters. The measured peak transmittance for each color filter was above 30%, exhibiting a wavelength spectrum with a full-width at half-maximum of approximately 100 nm. Simulation results of various structures with different cap layers revealed the enhanced coupling between surface plasmon resonances at both sides of the metal film in a symmetrical configuration. It was found that gratings with as few as three periods were sufficient to demonstrate filtering. The effect of metal thickness and hole size was investigated in detail. PMID- 20588538 TI - Quantitative SLM-based Differential Interference Contrast imaging. AB - We describe the implementation of quantitative Differential Interference Contrast (DIC) Microscopy using a spatial light modulator (SLM) as a flexible Fourier filter in the optical path. The experimental arrangement allows for the all electronic acquisition of multiple phase shifted DIC-images at video rates which are analyzed to yield the optical path length variation of the sample. The resolution of the technique is analyzed by retrieving the phase profiles of polystyrene spheres in immersion oil, and the method is then applied for quantitative imaging of biological samples. By reprogramming the diffractive structure displayed at the SLM it is possible to record the whole set of phase shifted DIC images simultaneously in different areas of the same camera chip. This allows for quantitative snap-shot imaging of a sample, which has applications for the investigation of dynamic processes. PMID- 20588539 TI - Efficient coupling and field enhancement for the nano-scale: plasmonic needle. AB - Theoretical demonstration of efficient coupling and power concentration of radially-polarized light on a conical tip of plasmonic needle is presented. The metallic needle is grown at the center of radial plasmonic grating, engraved in a metal surface. The electromagnetic field distribution was evaluated by Finite Elements and Finite-Difference-Time-Domain methods. The results show that the field on the tip of the needle is significantly enhanced compared to the field impinging on the grating. The power enhancement exhibited a resonant behavior as a function of needle length and reached values of approximately 10(4). Test samples for few types of characterization schemes were fabricated. PMID- 20588540 TI - Pump-tunable continuous-wave singly resonant optical parametric oscillator from 2.5 to 4.4 microm. AB - We report a continuous-wave singly resonant optical parametric oscillator pumped by a widely tunable titanium-doped sapphire ring laser. It produces up to 0.8 W of mid-infrared power. The wavelength can be tuned in a few seconds from 2.5 to 3.5 microm or from 3.4 to 4.4 microm and scanned up to 40 GHz without mode-hops by only changing the pump beam wavelength. Spectroscopic capability is demonstrated by measuring parts of the photoacoustic absorption spectrum of NH(3) near 3196 cm(-1). PMID- 20588541 TI - A non-reflecting metamaterial slab under the finite-embedded coordinate transformation. AB - Under the restrictions that the mapping functions of transformation are defined in extended two-dimensional (2D) forms and the incident waves are 2D propagating fields, the conditions for non-reflecting boundaries in a finite-embedded coordinate transformation metamaterial slab are derived. By exploring several examples, including some reported in the literatures and some novel ones developed in this study, we show that our approach can be efficiently used to determine the condition for a finite-embedded coordinate transformed metamaterial slab to be non-reflecting. PMID- 20588543 TI - Modified hybrid subcarrier/amplitude/ phase/polarization LDPC-coded modulation for 400 Gb/s optical transmission and beyond. AB - In this paper, we present a modified coded hybrid subcarrier/ amplitude/phase/polarization (H-SAPP) modulation scheme as a technique capable of achieving beyond 400 Gb/s single-channel transmission over optical channels. The modified H-SAPP scheme profits from the available resources in addition to geometry to increase the bandwidth efficiency of the transmission system, and so increases the aggregate rate of the system. In this report we present the modified H-SAPP scheme and focus on an example that allows 11 bits/Symbol that can achieve 440 Gb/s transmission using components of 50 Giga Symbol/s (GS/s). PMID- 20588544 TI - Single-shot picosecond interferometry with one-nanometer resolution for dynamical surface morphology using a soft X-ray laser. AB - Using highly coherent radiation at a wavelength of 13.9 nm from a Ag-plasma soft X-ray laser, we constructed a pump-and-probe interferometer based on a double Lloyd's mirror system. The spatial resolutions are evaluated with a test pattern, showing 1.8-mum lateral resolution, and 1-nm depth sensitivity. This instrument enables a single-shot observation of the surface morphology with a 7-ps time resolution. We succeeded in observing a nanometer scale surface dilation of Pt films at the early stage of the ablation process initiated by a 70 fs near infrared pump pulse. PMID- 20588545 TI - Tunable photonic metamaterials in the near infrared frequencies. AB - By using interference lithography and electron-beam evaporation and lift-off, we fabricate a series of pairs of elliptical metal-dielectric-metal plates with varying lengths of major and minor axis. Transmission measurements reveal that the magnetic response of the structures show linear shift with both the axis length of the elliptical plates and polarization direction of the incident light in a region of from 1.26microm to 2.10 microm. Our structures offer opportunities for oversimply constructing bulk photonic metamaterials for various applications. PMID- 20588546 TI - Design of Arrayed-Waveguide Grating Routers for use as optical OFDM demultiplexers. AB - All-optical OFDM uses optical techniques to multiplex together several modulated lightsources, to form a band of subcarriers that can be considered as one wavelength channel. The subcarriers have a frequency separation equal to their modulation rate. This means that they can be demultiplexed without any cross-talk between them, usually with a Discrete Fourier Transform (DFT), implemented optically or electronically. Previous work has proposed networks of optical couplers to implement the DFT. This work shows that the topology of an Arrayed Grating Waveguide Router (AWGR) can be used to perform the demultiplexing, and that the AWGR can be considered as a serial-to-parallel converter followed by a DFT. The simulations show that the electrical bandwidths of the transmitter and receiver are critical to orthogonal demultiplexing, and give insight into how crosstalk occurs in all-optical OFDM and coherent-WDM systems using waveforms and spectra along the system. Design specifications for the AWGR are developed, and show that non-uniformity will lead to crosstalk. The compensation of dispersion and the applications of these techniques to 'coherent WDM' systems using Non Return to Zero modulation is discussed. PMID- 20588547 TI - Simulations of vacuum laser acceleration: hidden errors from particle's initial positions. AB - Simulation of vacuum laser acceleration, because of its scheme's simplicity, attracts many people involved in. However, how to put the particle in the initial positions in the field has not been considered seriously in some such schemes. An inattentive choice of electron's initial conditions may lead to misleading results. Here we show that arbitrarily placing the particle within the laser field leads to an overestimation of its energy gain, and offer suggestions for selecting appropriate initial conditions. PMID- 20588548 TI - Field penetrations in photonic crystal Fano reflectors. AB - We report here the field and modal characteristics in photonic crystal (PC) Fano reflectors. Due to the tight field confinement and the compact reflector size, the cavity modes are highly localized and confined inside the single layer Fano reflectors, with the energy penetration depth of only 100nm for a 340 nm thick Fano reflector with a design wavelength of 1550 nm. On the other hand, the phase penetration depths, associated with the phase discontinuity and dispersion properties of the reflectors, vary from 2000 nm to 4000 nm, over the spectral range of 1500 nm to 1580 nm. This unique feature offers us another design freedom of the dispersion engineering for the cavity resonant mode tuning. Additionally, the field distributions are also investigated and compared for the Fabry-Perot cavities formed with PC Fano reflectors, as well conventional DBR reflectors and 1D sub-wavelength grating reflectors. All these characteristics associated with the PC Fano reflectors enable a new type of resonant cavity design for a large range of photonic applications. PMID- 20588549 TI - Nanoscale imaging using deep ultraviolet digital holographic microscopy. AB - A deep ultraviolet off-axis digital holographic microscope (DHM) is presented. The microscope has been arranged with as least as possible optical elements in the imaging path to avoid aberration due to the non-perfect optical elements. A high resolution approach has been implemented in the setup using oblique illumination to overcome the limitation introduced by the optical system. To examine the resolution of the system a nano-structured template has been designed and the result confirms the submicron and nanoscale resolution of the arranged DHM setup. PMID- 20588550 TI - Imitating the Cherenkov radiation in backward directions using one-dimensional photonic wires. AB - A novel radiation emission from traveling charged particles in vacuum is theoretically demonstrated. This radiation is conical as in the Cherenkov radiation, but emerges in backward directions of the particle trajectories. The basic mechanism of the radiation is the Smith-Purcell effect via the interaction between the charged particles and a circular-symmetric photonic wire with a one dimensionally periodic dielectric function. The wire exhibits the photonic band structure characterized with angular momentum. The charged particle can resonantly excite the photonic band modes with particular angular momentum, depending on the particle velocity. A simple kinetics of the Smith-Purcell effect enables us to design the conical radiation emitted in backward directions. Numerical results of the backward radiation are also presented for a metallic wire with aligned air holes. PMID- 20588551 TI - Quantification of the fraction poorly deformable red blood cells using ektacytometry. AB - We describe a method to obtain the fraction of poorly deformable red blood cells in a blood sample from the intensity pattern in an ektacytometer. In an ektacytometer red blood cells are transformed into ellipsoids by a shear flow between two transparent cylinders. The intensity pattern, due to a laser beam that is sent through the suspension, is projected on a screen. When measuring a healthy red blood cell population iso-intensity curves are ellipses with an axial ratio equal to that of the average red blood cell. In contrast poorly deformable cells result in circular iso-intensity curves. In this study we show that for mixtures of deformable and poorly deformable red blood cells, iso-intensity curves in the composite intensity pattern are neither elliptical nor circular but obtain cross-like shapes. We propose a method to obtain the fraction of poorly deformable red blood cells from those intensity patterns. Experiments with mixtures of poorly deformable and deformable red blood cells validate the method and demonstrate its accuracy. In a clinical setting our approach is potentially of great value for the detection of the fraction of sickle cells in blood samples of patients with sickle cell disease or to find a measure for the parasitemia in patients infected with malaria. PMID- 20588552 TI - Dynamic spectral-domain optical coherence elastography for tissue characterization. AB - A dynamic spectral-domain optical coherence elastography (OCE) imaging technique is reported. In this technique, audio-frequency compressive vibrations are generated by a piezoelectric stack as external excitation, and strain rates in the sample are calculated and mapped quantitatively using phase-sensitive spectral-domain optical coherence tomography. At different driving frequencies, this technique provides contrast between sample regions with different mechanical properties, and thus is used to mechanically characterize tissue. We present images of a three-layer silicone tissue phantom and rat tumor tissue ex vivo, based on quantitative strain rate. Both acquisition speed and processing speed are improved dramatically compared with previous OCE imaging techniques. With high resolution, high acquisition speed, and the ability to characterize the mechanical properties of tissue, this OCE technique has potential use in non destructive volumetric imaging and clinical applications. PMID- 20588553 TI - Polymer optical waveguide with multiple graded-index cores for on-board interconnects fabricated using soft-lithography. AB - We successfully fabricate a polymer optical waveguide with multiple graded-index (GI) cores directly on a substrate utilizing the soft-lithography method. A UV curable polymer (TPIR-202) supplied from Tokyo Ohka Kogyo Co., Ltd. is used, and the GI cores are formed during the curing process of the core region, which is similar to the preform process we previously reported. We experimentally confirm that near parabolic refractive index profiles are formed in the parallel cores (more than 50 channels) with 40 microm x 40 microm size at 250-microm pitch. Although the loss is still as high as 0.1 approximately 0.3 dB/cm at 850 nm, which is mainly due to scattering loss inherent to the polymer matrix, the scattering loss attributed to the waveguide's structural irregularity could be sufficiently reduced by a graded refractive index profile. For comparison, we fabricate step-index (SI)-core waveguides with the same materials by means of the same process. Then, we evaluate the inter-channel crosstalk in the SI- and GI core waveguides under almost the same conditions. It is noteworthy that remarkable crosstalk reduction (5 dB and beyond) is confirmed in the GI-core waveguides, since the propagating modes in GI-cores are tightly confined near the core center and less optical power is found near the core cladding boundary. This significant improvement in the inter-channel crosstalk allows the GI-core waveguides to be utilized for extra high-density on-board optical interconnections. PMID- 20588554 TI - Optical second-harmonic scattering from a non-diffusive random distribution of nonlinear domains. AB - We show that the weak second harmonic light generated from a random distribution of nonlinear domains of transparent Strontium Barium Niobate crystals can display a particularly intense generation in the forward direction. By using a theoretical model able to analyze the optical response of arbitrary distributions of three-dimensional nonlinear volumes of any shape, we found that the physical origin of this observation can be explained in terms of the scattering of light by a single nonlinear domain. PMID- 20588555 TI - An occlusion insensitive adaptive focus measurement method. AB - This paper proposes a new focus measurement method for Depth From Focus to recover depth of scenes. The method employs an all-focused image of the scene to address the focus measure ambiguity problem of the existing focus measures in the presence of occlusions. Depth discontinuities are handled effectively by using adaptively shaped and weighted support windows. The size of the support window can be increased conveniently for more robust depth estimation without introducing any window size related Depth From Focus problems. The experiments on the real and synthetically refocused images show that the introduced focus measurement method works effectively and efficiently in real world applications. PMID- 20588556 TI - Phase control of double-pass cascaded SHG/DFG wavelength conversion in Ti:PPLN channel waveguides. AB - The efficiency of wavelength conversion by cascaded second harmonic generation / difference frequency generation (cSHG/DFG) in Ti:PPLN waveguides can be considerably improved by using a double-pass configuration. However, due to the wavelength dependent phase change by the dielectric folding mirror phase compensation is required to maintain an optimum power transfer. We experimentally investigated three different approaches and improved the wavelength conversion efficiency up to 9 dB in comparison with the single-pass configuration. PMID- 20588557 TI - Ultrafast spatiotemporal relaxation dynamics of excited electrons in a metal nanostructure detected by femtosecond-SNOM. AB - Ultrahigh spatiotemporal resolved pump-probe signal near a gold nano-slit is detected by femtosecond-SNOM. By employing two-color pump-probe configuration and probing at the interband transition wavelength of the gold, signal contributed by surface plasmon polariton is avoided and spatiotemporal evolvement of excited electrons is successfully observed. From the contrast decaying of the periodical distribution of the pump-probe signal, ultrafast diffusion of excited electrons with a time scale of a few hundred femtoseconds is clearly identified. For comparison, such phenomenon cannot be observed by the one-color pump-probe configuration. PMID- 20588558 TI - Longitudinal optical trapping and sizing of aerosol droplets. AB - We present evidence that aerosol droplets, approximately 1-2microm in diameter, can be optically bound over a 4mm distance within a volume formed by the overlap of the central cores and rings of two counterpropagating Bessel beams. The sizes of the individual polydisperse aerosol particles can be estimated from the angular variation of the elastic light scattering. Scattered light from the two orthogonally polarized trapping beams and from a Gaussian probe beam of different wavelength can be used to provide independent estimations of size. The coalescence of two droplets was observed and characterized. PMID- 20588559 TI - Miniaturized fiber taper reflective interferometer for high temperature measurement. AB - We present an ultra-small all-silica high temperature sensor based on a reflective Fabry-Perot modal interferometer (FPMI). Our FPMI is made of a micro cavity (approximately 4.4 microm) directly fabricated into a fiber taper probe less than 10 mum in diameter. Its sensing head is a miniaturized single mode multimode fiber configuration without splicing. The sensing mechanism of FPMI is the interference among reflected fundamental mode and excited high-order modes at the end-faces. Its temperature sensitivity is approximately 20 pm/degrees C near the wavelength of 1550 nm. This kind of sensor can work in harsh environments with ultra-large temperature gradient, but takes up little space because of its unique geometry and small size. PMID- 20588560 TI - Fabrication and characterization of linear diffusers based on concave micro lens arrays. AB - We present a new approach of beam homogenizing elements based on a statistical array of concave cylindrical microlens arrays. Those elements are used to diffuse light in only one direction and can be employed together with fly's eye condensers to generate a uniform flat top line for high power coherent light sources. Conception, fabrication and characterization for such 1D diffusers are presented in this paper. PMID- 20588561 TI - Temporal-imaging system with simple external-clock triggering. AB - We demonstrate a temporal imaging system based on parametric mixing that allows simple triggering from an external clock by using a time-lens-based pump laser. We integrate our temporal imaging system into a time-to-frequency measurement scheme and demonstrate the ability to perform characterization of temporal waveforms with 1.4-ps resolution and a 530-ps record length. We also integrate our system into a temporal-magnification scheme and demonstrate single-shot operation with a 113 x magnification factor, 1.5-ps resolution, and 220-ps record length. PMID- 20588562 TI - Slow-light enhanced absorption in a hollow-core fiber. AB - Light traversing a hollow-core photonic band-gap fiber may experience multiple reflections and thereby a slow-down and enhanced optical path length. This offers a technologically interesting way of increasing the optical absorption of an otherwise weakly absorbing material which can infiltrate the fibre. However, in contrast to structures with a refractive index that varies along the propagation direction, like Bragg stacks, the translationally invariant structures studied here feature an intrinsic trade-off between light slow-down and filling fraction that limits the net absorption enhancement. We quantify the degree of absorption enhancement that can be achieved and its dependence on key material parameters. By treating the absorption and index on equal footing, we demonstrate the existence of an absorption-induced saturation of the group index that itself limits the maximum absorption enhancement that can be achieved. PMID- 20588563 TI - A standing-wave interpretation of plasmon resonance excitation in split-ring resonators. AB - In this study, we investigated the plasmon resonances of split-ring resonators (SRRs) numerically at incident angles of 0 and 45 degrees under illumination with linearly and circularly polarized waves. At 45 degrees incidence, perpendicular polarized waves excited distinct odd plasmon modes; the difference in the reflections of right and left circularly polarized incident radiation was very large. From simulated near field plots, we found that the parallelism of the incident electric field and the induced plasmon current was the key factor affecting excitation. We propose the use of a parallelism factor (P-factor), based on a standing-wave approach, to characterize the ability of incident fields to excite multiple plasmon resonance currents. The mechanism of the field and current parallelism can explain the resonance behavior of SRRs when considering the polarization state, incident angle, and geometry of the SRR. PMID- 20588564 TI - Role of Coulomb focusing on the electron transverse momentum of Above-Threshold Ionization. AB - We have investigated the 2D photoelectron momentum spectra for ATI of atoms exposed to linearly polarized pulses by quantum mechanical calculations. By comparing the 2D momentum spectra for the long-range and short-range Coulomb potentials, the focusing of the electron transverse momentum by the long-range interaction is clearly revealed. Analysis indicates that the Coulomb attraction of the parent core to the returning electron is responsible for the focusing of the electron transverse momentum. Moreover, the strong dependence of the focusing of the electron transverse momentum on the laser wavelength and intensity is discussed. PMID- 20588566 TI - Optics in Energy: the power of optical solutions. AB - Editorial for the inaugural issue of Energy Express. PMID- 20588565 TI - Simultaneous existence of phononic and photonic band gaps in periodic crystal slabs. AB - We discuss the simultaneous existence of phononic and photonic band gaps in a periodic array of holes drilled in a Si membrane. We investigate in detail both the centered square lattice and the boron nitride (BN) lattice with two atoms per unit cell which include the simple square, triangular and honeycomb lattices as particular cases. We show that complete phononic and photonic band gaps can be obtained from the honeycomb lattice as well as BN lattices close to honeycomb. Otherwise, all investigated structures present the possibility of a complete phononic gap together with a photonic band gap of a given symmetry, odd or even, depending on the geometrical parameters. PMID- 20588567 TI - Thermochemical production of fuels with concentrated solar energy. AB - This review article develops some of the underlying science for converting concentrated solar energy into chemical fuels and presents examples of solar thermochemical processes and reactors. PMID- 20588568 TI - Metal glass vacuum tube solar collectors are approaching lower-medium temperature heat application. AB - Solar thermal collectors are widely used worldwide mainly for hot water preparation at a low temperature (less than 80?C). Applications including many industrial processes and central air conditioning with absorption chillers, instead require lower-medium temperature heat (between 90 degrees C and 150 degrees C) to be driven when using solar thermal energy. The metal absorber glass vacuum tube collectors (MGVT) are developed for this type of applications. Current state-of-art and possible future technology development of MGVT are presented. PMID- 20588569 TI - Solar concentrator modules with silicone-on-glass Fresnel lens panels and multijunction cells. AB - High-efficiency multijunction (MJ) solar cells, being very expensive to manufacture, should only be used in combination with solar concentrators in terrestrial applications. An essential cost reduction of electric power produced by photovoltaic (PV) installations with MJ cells, may be expected by the creation of highly-effective, but inexpensive, elements for optical concentration and sun tracking. This article is an overview of the corresponding approach under development at the Ioffe Physical Technical Institute. The approach to R&D of the solar PV modules is based on the concepts of sunlight concentration by small aperture area Fresnel lenses and "all-glass" module design. The small-aperture area lenses are arranged as a panel with silicone-on-glass structure where the glass plate serves as the front surface of a module. In turn, high-efficiency InGaP/(In)GaAs/Ge cells are arranged on a rear module panel mounted on a glass plate which functions as a heat sink and integrated protective cover for the cells. The developed PV modules and sun trackers are characterized by simple design, and are regarded as the prototypes for further commercialization. PMID- 20588570 TI - High performance Fresnel-based photovoltaic concentrator. AB - In order to achieve competitive system costs in mass-production, it is essential that CPV concentrators incorporate sufficient manufacturing tolerances. This paper presents an advanced concentrator optic comprising a Fresnel lens and a refractive secondary element, both with broken rotational symmetry, an optic producing both the desired light concentration with high tolerance (high acceptance angle) as well as an excellent light homogenization by Kohler integration. This concentrator compares well with conventional Fresnel-based CPV concentrators. PMID- 20588571 TI - Focus issue: solar concentrators. Introduction. AB - Introduction to the Solar Concentrators Focus Issue of Energy Express. PMID- 20588572 TI - Aplanatic optics for solar concentration. AB - Aplanats are imaging optics that completely eliminate both spherical aberration and coma. They can fulfill the practical virtues of permitting sizable gaps between the absorber and the optic, as well as compactness. However, the ability of aplanats to efficiently approach the thermodynamic limit to flux concentration and optical tolerance had remained unrecognized. Both fundamental and applied aspects of dual-mirror aplanats are reviewed and elaborated, motivated by the exigencies of tenable, maximum-performance solar concentrators, including examples from commercial concentrator photovoltaics (CPV). Promising designs for future photovoltaic concentrators are also identified, illustrating how pragmatic constraints translate into devising fundamentally new optics. PMID- 20588573 TI - Thermodynamic efficiency of solar concentrators. AB - The optical thermodynamic efficiency is a comprehensive metric that takes into account all loss mechanisms associated with transferring flux from the source to the target phase space, which may include losses due to inadequate design, non ideal materials, fabrication errors, and less than maximal concentration. We discuss consequences of Fermat's principle of geometrical optics and review etendue dilution and optical loss mechanisms associated with nonimaging concentrators. We develop an expression for the optical thermodynamic efficiency which combines the first and second laws of thermodynamics. As such, this metric is a gold standard for evaluating the performance of nonimaging concentrators. We provide examples illustrating the use of this new metric for concentrating photovoltaic systems for solar power applications, and in particular show how skewness mismatch limits the attainable optical thermodynamic efficiency. PMID- 20588574 TI - 30 kW concentrator photovoltaic system using dome-shaped Fresnel lenses. AB - A 30 kW concentrator photovoltaic power plant was constructed and has started operation with the following new technologies: A new Concentrating PhotoVoltaic (CPV) tracker developed for high wind area like Korea and Japan by Daido Steel. (The power consumption of the tracking motors was only 19.6 W, namely 0.07% of the rated power.) With improved optics that reduce the mismatch losses associated with optical aberrations, an efficiency of 25.8% was achieved under standard testing conditions (STC) even in a large 23.8 m(2) array size. A rapid installation sequence was developed. It was designed for long-term power supply to a local sewage center. Peak power corresponds to 10% of the demand. As a result, the system performance ratio was 0.87, and the capacity factor was 11.7%. The energy generation per rated power was 1,020 kWh/kWp. While it is true that CPV systems perform better in dry and high irradiance areas, our 30 kW system installed in a cloudy area like Japan, showed satisfactory performance. PMID- 20588575 TI - Pushing concentration of stationary solar concentrators to the limit. AB - We give the theoretical limit of concentration allowed by nonimaging optics for stationary solar concentrators after reviewing sun-earth geometry in direction cosine space. We then discuss the design principles that we follow to approach the maximum concentration along with examples including a hollow CPC trough, a dielectric CPC trough, and a 3D dielectric stationary solar concentrator which concentrates sun light four times (4x), eight hours per day year around. PMID- 20588576 TI - Multijunction solar cells for conversion of concentrated sunlight to electricity. AB - Solar-cell efficiencies have exceeded 40% in recent years. The keys to achieving these high efficiencies include: 1) use of multiple materials that span the solar spectrum, 2) growth of these materials with near-perfect quality by using epitaxial growth on single-crystal substrates, and 3) use of concentration. Growth of near-perfect semiconductor materials is possible when the lattice constants of the materials are matched or nearly matched to that of a single crystal substrate. Multiple material combinations have now demonstrated efficiencies exceeding 40%, motivating incorporation of these cells into concentrator systems for electricity generation. The use of concentration confers several key advantages. PMID- 20588577 TI - Dye alignment in luminescent solar concentrators: I. Vertical alignment for improved waveguide coupling. AB - Luminescent solar concentrators (LSCs) use dye molecules embedded in a flat-plate waveguide to absorb solar radiation. Ideally, the dyes re-emit the absorbed light into waveguide modes that are coupled to solar cells. But some photons are always lost, re-emitted through the face of the LSC and coupled out of the waveguide. In this work, we improve the fundamental efficiency limit of an LSC by controlling the orientation of dye molecules using a liquid crystalline host. First, we present a theoretical model for the waveguide trapping efficiency as a function of dipole orientation. Next, we demonstrate an increase in the trapping efficiency from 66% for LSCs with no dye alignment to 81% for a LSC with vertical dye alignment. Finally, we show that the enhanced trapping efficiency is preserved for geometric gains up to 30, and demonstrate that an external diffuser can alleviate weak absorption in LSCs with vertically-aligned dyes. PMID- 20588578 TI - Dye alignment in luminescent solar concentrators: II. Horizontal alignment for energy harvesting in linear polarizers. AB - We describe Linearly Polarized Luminescent Solar Concentrators (LP-LSCs) to replace conventional, purely absorptive, linear polarizers in energy harvesting applications. As a proof of concept, we align 3-(2-Benzothiazolyl)-N,N diethylumbelliferylamine (Coumarin 6) and 4-dicyanomethyl-6-dimethylaminostiryl 4H-pyran (DCM) dye molecules linearly in the plane of the substrate using a polymerizable liquid crystal host. We show that up to 38% of the photons polarized on the long axis of the dye molecules can be coupled to the edge of the device for an LP-LSC based on Coumarin 6 with an order parameter of 0.52. PMID- 20588579 TI - Single stage transmission type broadband solar concentrator. AB - In this paper, a single stage solar cell concentrator is designed and discussed. The proposed concentrator consists of refraction prisms and total internal reflection prisms in the inner and outer areas, respectively. In order to compensate for dispersion, all odd zones gather the light onto the -D position, while all even zones gather the light onto the + D position. Finally, the hybrid concentrator achieves optical efficiency of 89.8% for normally incident light without an antireflection coating. An acceptance angle of +/- 0.78 degree at 1 dB loss is achieved without using additional secondary optics. In addition, the fabrication tolerance is also analyzed. PMID- 20588580 TI - Evolutionary algorithm for optimization of nonimaging Fresnel lens geometry. AB - In this study, an evolutionary algorithm (EA), which consists of genetic and immune algorithms, is introduced to design the optical geometry of a nonimaging Fresnel lens; this lens generates the uniform flux concentration required for a photovoltaic cell. Herein, a design procedure that incorporates a ray-tracing technique in the EA is described, and the validity of the design is demonstrated. The results show that the EA automatically generated a unique geometry of the Fresnel lens; the use of this geometry resulted in better uniform flux concentration with high optical efficiency. PMID- 20588581 TI - Enhanced light trapping in thin-film solar cells by a directionally selective filter. AB - A directionally selective multilayer filter is applied to a hydrogenated amorphous silicon solar cell to improve the light trapping. The filter prevents non-absorbed long-wavelength photons from leaving the cell under oblique angles leading to an enhancement of the total optical path length for weakly absorbed light within the device by a factor of kappa(r) = 3.5. Parasitic absorption in the contact layers limits the effective path length improvement for the photovoltaic quantum efficiency to a factor of kappa(EQE) = 1.5. The total short circuit current density increases by DeltaJ(sc) = 0.2 mAcm(-2) due to the directional selectivity of the Bragg-like filter. PMID- 20588582 TI - Enhanced absorption in optically thin solar cells by scattering from embedded dielectric nanoparticles. AB - We present a concept for improving the efficiency of thin-film solar cells via scattering from dielectric particles. The particles are embedded directly within the semiconductor absorber material with sizes on the order of one wavelength. Importantly, this geometry is fully compatible with the use of an anti-reflective coating (ARC) to maximize light capture. The concept is demonstrated through finite-difference time domain (FDTD) simulations of spherical SiO(2) particles embedded within a 1.0 microm layer of crystalline silicon (c-Si) utilizing a 75 nm ARC of Si(3)N(4). Several geometries are presented, with gains in absorbed photon flux occurring in the red end of the spectrum where silicon absorption is weak. The total integrated absorption of incident photon flux across the visible AM-1.5 spectrum is on the order of 5-10% greater than the same geometry without any dielectric scatterers. PMID- 20588583 TI - Photoelectrolysis of water: Solar hydrogen--achievements and perspectives. AB - Thermodynamic analysis of energy conversion from light-to-chemical, light-to electric and electric-to-chemical is presented by the case study of water photoelectrolysis on TiO(2) surface. It is demonstrated that at the current state of-the-art energy conversion efficiency of water photoelectrolysis can be increased approximately 17 times by separating the processes of solar-to-electric and electric-to-chemical energy conversion and optimizing them independently. This allows to mitigate a high overvoltage of oxygen evolution reaction with respect to thermodynamic E(0)(O(2)/H(2)O) = 1.23 V potential as well as spectrally narrow absorbtivity of solar light by TiO(2) which determine the low efficiency (approximately 1.0%) of direct light-to-chemical energy conversion. Numerical estimates are provided illustrating practical principles for optimization of the solar energy conversion and storage processes. PMID- 20588584 TI - Towards an aligned luminophore solar concentrator. AB - Luminescent solar concentrators promise to reduce the cost of solar energy, but are hindered by a number of losses. Escape of luminescence through the large waveguide-air interfaces can be attenuated through alignment of the optical transition dipole of the luminophore along the waveguide surface normal, directing the maximum possible proportion of luminescence into waveguide modes. We demonstrate such alignment using a guest-host dye-doped liquid crystal sandwiched between conductive glass slides. Application of a potential while illuminating through a narrow edge caused a drop in the intensity of luminescence escaping the large surfaces, and an increase in the intensity of light escaping the narrow edges of the system. This is explained in terms of alignment of the transition dipoles of the dye. We discuss implementation in a luminescent solar concentrator. PMID- 20588585 TI - UV-ozone-treated ultra-thin NaF film as anode buffer layer on organic light emitting devices. AB - An ultra-thin NaF film was thermally deposited between ITO and NPB as the buffer layer and then treated with the ultraviolet (UV) ozone, in the fabrication of organic light emitting diodes (ITO/NaF/NPB/Alq(3)/LiF/Al) to study its effect on hole-injection properties. The treatment drastically transforms the role of NaF film from hole-blocking to hole-injecting. This transformation is elucidated using hole-only devices, energy band measurement, surface energy, surface polarity, and X-ray photoelectron spectra. With the optimal thickness (3 nm) of the UV-ozone-treated NaF layer, the device performance is significantly improved, with a turn-on voltage, maximum luminance, and maximum current efficiency of 2.5 V, 15700 cd/m(2), and 4.9 cd/A, respectively. Results show that NaF film is not only a hole-blocking layer, but also a promising hole-injecting layer after UV ozone treatment. PMID- 20588586 TI - Enhancement of light scattering and photoluminescence in electrospun polymer nanofibers. AB - Poly(methyl methacrylate) nanofibers with desired fiber diameters that ranged from 336 to 896 nm were electrospun as light scattering and propagation materials. The light scattering behavior of these samples as a function of the fiber diameter and fiber deposition thickness was examined by UV-vis spectrophotometry, which revealed the scattering bands in the absorption spectra. The scattering bands of these nanofibers were linearly proportional to the fiber diameter, which shows good agreement with a scattering model based on the Mie theory. The light scattering and prolonged light path lengths in the nanofiber scaffolds were monitored and quantified by the photoluminescence of a fluorescent dye, Coumarin 6, which was preloaded into the polymer nanofibers. The photoluminescence after proper normalization showed a second-order dependence on the dye loading per unit area, which is significantly different from the spin coated thin-film samples following a first-order relationship. Nonlinear photoluminescence enhancements indicated prolonged light path lengths and multiple light absorptions within the fiber scaffolds as a result of light scattering. Even with relatively broad scattering band widths, the light scattering and photoluminescence of the electrospun nanofibers exhibited considerable wavelength selectivity, especially as the scattering bands overlapped with the excitation wavelengths of the fluorescence reagent. PMID- 20588587 TI - A reflecting Pockels cell with aperture scalable for high average power multipass amplifier systems. AB - In high average power multi-pass amplifier systems, Pockels cell, used for isolating and controlling number of passes, encounters both limitation of aperture and thermo-effects. We propose and demonstrate for the first time, as far as we know, a reflecting Pockels cell (RPC) which is longitudinally excited based on KD*P utilizing matched a discharge chamber and a copper plate as electrodes. In the RPC, electro-optic crystal can be longitudinally conduction cooled. This device, with a 40 mm x 40 mm clear aperture, can be scaled to larger, and driven by one low voltage pulse. Excellent switching efficiency, high static extinction ratio, and negligible thermo-effects have been achieved. PMID- 20588588 TI - Modified blackbody radiation spectrum of a selective emitter with application to incandescent light source design. AB - Using a selective emitter with high emissivity in the visible wavelength region and low emissivity in the infrared wavelength region, we reduced the infrared contribution to the blackbody radiation spectrum and shifted the peak emission to shorter wavelengths. We made precise measurements of thermal radiation loss. The conversion efficiency from input electric power to visible light radiation was quantitatively evaluated with high accuracy. Using the proposed selective emitter, the conversion efficiencies in excess of 95% could be produced. Our conclusions pave the way for the design of incandescent lamps with luminous efficiencies exceeding 400 lm/W. PMID- 20588589 TI - Conformal phosphor coating using pulsed spray to reduce color deviation of white LEDs. AB - This work presents a novel "pulsed spray (PS)" process for the coating of yellow YAG:Ce(3+) phosphor on blue InGaN-based light emitting diodes (LEDs). To coat a phosphor layer of high quality on an LED chip surface, the PS approach is used and studied because of the uniform color distribution, providing a wide range of color temperatures. This PS coating approach applies phosphor by exploiting mechanical principles without risk of chemical pollution. Additionally, it can be applied to wire-bonded LEDs and an array of LED chips on a substrate to fabricate a large-area, planar illumination system of high optical quality, which is easy to manufacture. PMID- 20588590 TI - Absorption enhancement of an amorphous Si solar cell through surface plasmon induced scattering with metal nanoparticles. AB - The simulation results of absorption enhancement in an amorphous-Si (a-Si) solar cell by depositing metal nanoparticles (NPs) on the device top and embedding metal NPs in a layer above the Al back-reflector are demonstrated. The absorption increase results from the near-field constructive interference of electromagnetic waves in the forward direction such that an increased amount of sunlight energy is distributed in the a-Si absorption layer. Among the three used metals of Al, Ag, and Au, Al NPs show the most efficient absorption enhancement. Between the two used NP geometries, Al nanocylinder (NC) are more effective in absorption enhancement than Al nanosphere (NS). Also, a random distribution of isolated metal NCs can lead to higher absorption enhancement, when compared with the cases of periodical metal NC distributions. Meanwhile, the fabrication of both top and bottom Al NCs in a solar cell results in further absorption enhancement. Misalignments between the top and bottom Al NCs do not significantly reduce the enhancement percentage. With a structure of vertically aligned top and bottom Al NCs, solar cell absorption can be increased by 52%. PMID- 20588591 TI - Integration of non-Lambertian LED and reflective optical element as efficient street lamp. AB - A cost effective, high throughput, and high yield method for the increase of street lamp potency was proposed in this paper. We integrated the imprinting technology and the reflective optical element to obtain a street lamp with high illumination efficiency and without glare effect. The imprinting technique can increase the light extraction efficiency and modulate the intensity distribution in the chip level. The non-Lambertian light source was achieved by using imprinting technique. The compact reflective optical element was added to efficiently suppress the emitting light intensity with small emitting angle for the uniform of illumination intensity and excluded the light with high emitting angle for the prevention of glare. Compared to the conventional street lamp, the novel design has 40% enhancement in illumination intensity, the uniform illumination and the glare effect elimination. PMID- 20588592 TI - Novel yellowish-orange Sr8Al12O24S2:Eu2+ phosphor for application in blue light emitting diode based white LED. AB - A new yellowish-orange phosphor, Sr(8)Al(12)O(24)S(2):Eu(2+), was synthesized by the solid-state method and its photoluminescence properties were investigated by excitation and emission spectra. Its excitation band is extending from 400-500 nm, which is adaptable to the emission band of blue LED chips (450-470 nm). Upon the excitation of 450 nm light, the phosphor exhibits strong yellowish-orange emission centered at 605 nm with good thermal stability. A white light-emitting diode (W-LED) that consists of a blue LED chip (approximately 470 nm) and a (Sr(0.92)Eu(0.08))(8)Al(12)O(24)S(2) phosphor is demonstrated. The CIE1931 chromaticity coordinates (x, y) are (0.34, 0.25), the correlated color temperature (CCT) is 4300 K, and the luminous efficacy of this W-LED is 14.2 lm/W at room temperature and with a forward-bias current of 400 mA. PMID- 20588593 TI - Light trapping in ultrathin plasmonic solar cells. AB - We report on the design, fabrication, and measurement of ultrathin film a-Si:H solar cells with nanostructured plasmonic back contacts, which demonstrate enhanced short circuit current densities compared to cells having flat or randomly textured back contacts. The primary photocurrent enhancement occurs in the spectral range from 550 nm to 800 nm. We use angle-resolved photocurrent spectroscopy to confirm that the enhanced absorption is due to coupling to guided modes supported by the cell. Full-field electromagnetic simulation of the absorption in the active a-Si:H layer agrees well with the experimental results. Furthermore, the nanopatterns were fabricated via an inexpensive, scalable, and precise nanopatterning method. These results should guide design of optimized, non-random nanostructured back reflectors for thin film solar cells. PMID- 20588594 TI - Analysis of the emission profile in organic light-emitting devices. AB - In this paper, numerical algorithms for extraction of optoelectronic material and device parameters in organic light-emitting devices (OLEDs) are presented and tested for their practical use. Of particular interest is the extraction of the emission profile and the source spectrum. A linear and a nonlinear fitting method are presented and applied to emission spectra from OLEDs in order to determine the shape of the emission profile and source spectrum. The motivation of the work is that despite the existence of advanced numerical models for optical and electronic simulation of OLEDs, their practical use is limited if methods for the extraction of model parameters are not well established. Two fitting methods are presented and compared to each other and validated on the basis of consistency checks. Our investigations show the impact of the algorithms on the analysis of realistic OLED structures. It is shown that both fitting methods p form reasonably well, even if the emission spectra to be analyzed are noisy. In some cases the nonlinear method performs slightly better and can achieve a perfect resolution of the emission profile. However, the linear method provides the advantage that no assumption on the mathematical shape of the emission profile has to be made. PMID- 20588595 TI - Patterning of flexible organic light emitting diode (FOLED) stack using an ultrafast laser. AB - A femtosecond laser has been successfully utilized for patterning thin Flexible Organic Light Emitting Diode (FOLED) structures of individual layer thickness around 100nm. The authors report in this paper a step-like ablation behavior at the layer interfaces which accounts for a local removal of entire layers. Various surface analyzing techniques are used to investigate the morphologies and chemical compositions within and in the vicinity of the ablation areas. This study opens a new avenue in selectively ablating different layers from a multilayer stack on flexible substrates using fs lasers allowing post deposition structuring of large area flexible organic electronic devices. PMID- 20588596 TI - Continuous-wave and passively Q-switched laser performance of LD-end-pumped 1062 nm Nd:GAGG laser. AB - Continuous-wave (CW) and passively Q-switched operations of LD-end-pumped Nd:Gd(3)Al(x)Ga(5-x)O(12) (Nd:GAGG) laser at 1062 nm were reported. The highest CW output power of 5.7 W was obtained, corresponding to an optical conversion efficiency and slope efficiency of 51.0% and 54.5%, respectively. The CW output efficiency of Nd:GAGG laser is comparable and even better than that of Nd:GGG. The passively Q-switched output was realized for the first time to our knowledge. In addition, a maximum output power of 1.12 W, a maximum pulse repetition rate of 39 kHz and a minimum pulse width of 6 ns were obtained by using Cr(4+):YAG as the saturable absorber. PMID- 20588597 TI - Unidirectional transmission in non-symmetric gratings made of isotropic material. AB - We achieve a broadband unidirectional transmission or One-way diffraction grating by cascading two parallel gratings made of isotropic material with different periods. In order to significantly reduce the reciprocal transmission of the zero order, one of them is chosen to be a subwavelength grating and designed as a wideband reflector for the incident-wave. It is demonstrated that more than 65 percent of the incident-wave energy can be transmitted unidirectionally with less than 0.22 percent transmission in the opposite direction at normal incidence for TE polarization. And, the relative bandwidth of the unidirectional transmission is greater than 10 percent. PMID- 20588598 TI - Tapered silicon optical fibers. AB - The tapering of silicon optical fibers is demonstrated using a fusion splicer. The silicon fibers are fabricated using a high pressure chemical deposition technique to deposit an amorphous silicon core inside a silica capillary and the tapering is performed in a separate post-process. Optical and material characterization has revealed a smooth transition region leading to a uniform tapered waist that are both simultaneously crystallized to yield a solid polysilicon core. The strong mode confinement and low taper loss measured in the silicon fibers verifies this tapering approach for the fabrication of structures with nanoscale core dimensions. PMID- 20588599 TI - High-power, variable repetition rate, picosecond optical parametric oscillator pumped by an amplified gain-switched diode. AB - We demonstrate a picosecond optical parametric oscillator (OPO) that is synchronously pumped by a fiber-amplified gain-switched laser diode. At 24W of pump power, up to 7.3W at 1.54microm and 3.1W at 3.4microm is obtained in separate output beams. The periodically poled MgO-doped LiNbO(3) OPO operates with ~17ps pulses at a fundamental repetition rate of 114.8MHz but can be switched to higher repetition rates up to ~1GHz. Tunabilty between 1.4microm and 1.7microm (signal) and 2.9microm and 4.4microm (idler) is demonstrated by translating the nonlinear crystal to access different poling-period gratings and typical M(2) values of 1.1 by 1.2 (signal) and 1.6 by 3.2 (idler) are measured at high power for the singly resonant oscillator. PMID- 20588600 TI - Shear stress mapping in microfluidic devices by optical tweezers. AB - We present an optical tweezer sensor for shear stress mapping in microfluidic systems of different internal geometries. The sensor is able to measure the shear stress acting on microspheres of different sizes that model cell based biological operations. Without the need for a spatial modulator or a holographic disk, the sensor allows for direct shear stress detection at arbitrary positions in straight and curved microfluidic devices. Analytical calculations are carried out and compared with the experimental results. It is observed that a decrease in the microsphere size results in an increase in the shear stress the particle experiences. PMID- 20588601 TI - Highly nonparaxial (1+1)-D subwavelength optical fields. AB - A general approach for describing (1+1)-D subwavelength optical field whose waist is much smaller than the wavelength is presented. Exploiting the vectorial Rayleigh-Sommerfeld diffraction theory, a suitable expansion in the ratio between the beam waist and the wavelength allows us to prove the a (1+1)D highly nonparaxial field is generally the product of a cylindrical wave carrier and an envelope which is angularly slowly varying. We apply our general approach to the case of highly nonparaxial Hermite-Gaussian beams whose description is fully analytical. PMID- 20588602 TI - Subpicosecond optical pulse compression via an integrated nonlinear chirper. AB - Photonic integrated circuits (PICs) capable of ultra-fast, signal processing are recognized as being fundamental for future applications involving ultra-short optical pulse propagation, including the ability to meet the exponentially growing global fiber-optic telecommunications bandwidth demand. Integrated all optical signal processors would carry substantial benefits in terms of performance, cost, footprint, and energy efficiency. Here, we demonstrate an optical pulse compressor based on an integrated nonlinear chirper, capable of operating on a sub-picosecond (> 1Tb/s) time scale. It is CMOS compatible and based on a 45cm long, high index doped silica glass waveguide we achieve pulse compression at relatively low input peak powers, due to the high nonlinearity and low linear and nonlinear losses of the device. The flexibility of this platform in terms of nonlinearity and dispersion allows the implementation of several compression schemes. PMID- 20588603 TI - Efficient wavelength conversion and net parametric gain via four wave mixing in a high index doped silica waveguide. AB - We demonstrate sub-picosecond wavelength conversion in the C-band via four wave mixing in a 45cm long high index doped silica spiral waveguide. We achieve an on/off conversion efficiency (signal to idler) of + 16.5dB as well as a parametric gain of + 15dB for a peak pump power of 38W over a wavelength range of 100nm. Furthermore, we demonstrated a minimum gain of + 5dB over a wavelength range as large as 200nm. PMID- 20588604 TI - Fiber probe based microfluidic raman spectroscopy. AB - We report a novel fiber probe based Raman detection system on a microfluidic platform where a split Raman probe is directly embedded into a polydimethylsiloxane (PDMS) chip. In contrast to previous Raman detection schemes in microfluidics, probe based detection offers reduced background and portability. Compared to conventional backscattering probe designs, the split fiber probe we used in this system, results in a reduced size and offers flexibility to modify the collection geometry to minimize the background generated by the fibers. Also our microfluidic chip design enables us to obtain an alignment free system. As a proof of concept we demonstrate the sensitivity of the device for urea detection at relevant human physiological levels with a low acquisition time. The development of this system on a microfluidic platform means portable, lab on a chip devices for biological analyte detection and environmental sensing using Raman spectroscopy are now within reach. PMID- 20588605 TI - Perfect focusing of scalar wave fields in three dimensions. AB - A method to design isotropic inhomogeneous refractive index distribution is presented, in which the scalar wave field solutions propagate exactly on an eikonal function (i.e., remaining constant on the Geometrical Optics wavefronts). This method is applied to the design of "dipole lenses", which perfectly focus a scalar wave field emitted from a point source onto a point absorber, in both two and three dimensions. Also, the Maxwell fish-eye lens in two and three dimensions is analysed. PMID- 20588606 TI - High performance InGaN/GaN nanorod light emitting diode arrays fabricated by nanosphere lithography and chemical mechanical polishing processes. AB - We fabricated InGaN/GaN nanorod light emitting diode (LED) arrays using nanosphere lithography for nanorod formation, PECVD (plasma enhanced chemical vapor deposition) grown SiO(2) layer for sidewall passivation, and chemical mechanical polishing for uniform nanorod contact. The nano-device demonstrates a reverse current 4.77nA at -5V, an ideality factor 7.35, and an optical output intensity 6807mW/cm(2) at the injection current density 32A/cm(2) (20mA). Moreover, the investigation of the droop effect for such a nanorod LED array reveals that junction heating is responsible for the sharp decrease at the low current. PMID- 20588607 TI - Power spectral analysis for optical trap stiffness calibration from high-speed camera position detection with limited bandwidth. AB - The use of camera imaging enables trap calibration for multiple particles simultaneously. For stiff traps, however, blur from image integration time affects the detected particle positions significantly. In this paper we use power spectral analysis to calibrate stiff optical traps, taking the effects of blur, aliasing and position detection error into account, as put forward by Wong and Halvorsen [Opt. Express 14, 12517 (2006)]. We find agreement with simultaneously obtained photodiode data and the expected relation of corner frequency fc with laser power, up to fc = 3.6 kHz for a Nyquist frequency of 1.25 kHz. Spectral analysis enables easy identification of the contribution of noise. We demonstrate the utility of our approach with simultaneous calibration of multiple holographic optical traps. PMID- 20588608 TI - Mode tailoring in a ridge-type periodically poled lithium niobate waveguide. AB - We present a simple and powerful method for mode generation and transformation in a ridge-type periodically poled lithium niobate (PPLN) waveguide by the use of second-order nonlinear effect and local-temperature-control technique. We show that a Hermite-Gaussian (HG) mode wave (among HG(00) to HG(22)) can be selectively generated via the quasi-phase-matching (QPM) nonlinear process in a PPLN waveguide by tuning the wavelength of fundamental wave or the temperature of the waveguide. As well, it is demonstrated that HG mode can be transformed into Laguerre-Gaussian (LG) one via combination of HG modes which are simultaneously generated in a single PPLN waveguide with local-temperature-control technique. PMID- 20588609 TI - Band-edge lasers based on randomly mixed photonic crystals. AB - By employing two-dimensional InGaAsP photonic band-edge lasers, we have experimentally demonstrated that a random mixture of two different photonic crystals (PCs) possesses a new band structure that is intermediate to that of the two host PCs. The photonic band-edges shift monotonically, but with a strong bowing effect, as the mixed PC system is systematically transformed from one PC to the other. The experimental observations are in excellent agreement with finite-difference time-domain simulations and model calculations based on virtual crystal approximation with compositional disorder effect included. PMID- 20588610 TI - Measurement of submicrometre diameters of tapered optical fibres using harmonic generation. AB - Applications of subwavelength-diameter optical fibres in nonlinear optics require precise knowledge of the submicrometre fibre waist diameter. We demonstrate a new technique for optical measurement of the diameter based on second- and third harmonic generation with an accuracy of better than 2%. To generate the harmonic light, inter-modal phase matching must be achieved. We find that the phase matching condition allows us to unambiguously deduce the fibre diameter from the wavelength of the harmonic light. High-resolution scanning electron microscope imaging is used to verify the results. PMID- 20588611 TI - Composite nanoparticle nanoslit arrays: a novel platform for LSPR mediated subwavelength optical transmission. AB - Near infrared transmission of light through subwavelength slit arrays is shown to be significantly influenced by resonant metallic nanoparticles placed within the structure. Experimental and calculated transmission spectra show how the size, orientation of the nanoparticles, and the period of the nanoslit array influence the maximum transmission wavelength, the magnitude of the transmission, and width of the resonance. These findings suggest that the localized surface plasmon resonance (LSPR) of metallic nanoparticles and their subsequent near and far field interactions can modulate the subwavelength transmission and bandwidth of nanoaperture array devices in optically thick metal films. PMID- 20588612 TI - All-optical, actively Q-switched fiber laser. AB - All-fiber lasers offer increased robustness and simplicity over other fiber laser systems. Current active Q-switching techniques for all-fiber lasers rely on electro-mechanical transducers to strain-tune an intra-cavity fiber-Bragg grating, which adds complexity and can lead to vibrational sensitivity. An all optical technique for achieving active Q-switched operation is a more elegant approach and would maintain the inherent robustness and simplicity of an all fiber laser system. In this work, we studied the optical tuning of a fiber-Bragg grating by resonant optical pumping and optimized it for application to active systems. We incorporated an optically-tunable fiber-Bragg grating into a fiber laser and demonstrated active Q-switching at 35 kHz with this all-optical, all fiber laser system. We highlight the potential to operate at >300 kHz with the current embodiment. To our knowledge, this is the first demonstration of an optically-driven active Q-switch in a fiber laser. Further potential to operate at MHz frequencies is discussed. PMID- 20588613 TI - Cooperative upconversion and optical gain in ion-beam sputter-deposited Er(x)Y(2 x)SiO(5) waveguides. AB - Single-phase, polycrystalline Er(x)Y(2-x)SiO(5) thin films were deposited by reactive ion-beam sputter deposition and rapid thermal annealing. Due to the crystalline nature, the silicate thin films provide peak Er(3+) emission cross section of 0.9 +/- 0.02 x 10(-20) cm(2) that is higher than that in silica. Optical gain, with near 60% inversion, is achieved via optical pumping of a single-mode, ridge-type waveguide with the silicate core with an Er concentration of 1.7 x 10(20) cm(-3). Analysis of pump-power dependence of the optical gain and spontaneous emission intensity of Er(3+) indicate that the gain is limited by cooperative upconversion process, whose coefficient is determined to be (8 +/- 3) x 10(-17) cm(3)/sec. PMID- 20588614 TI - Wavelength conversion by dynamically reconfiguring a nested photonic crystal cavity. AB - A dynamically reconfigurable nested photonic crystal cavity suitable for frequency conversion applications is proposed. Dynamic switching between two distinct cavities allows intermodal transition via spatially-uniform tuning of the refractive index. Exclusion of the initial resonant mode from the Eigen modes of the tuned cavity precludes the adiabatic wavelength conversion process. Multiple intermodal transitions are suppressed by the symmetry of the mode profiles of the two cavities. Over 90nm wavelength shift (from L-band to the S band) is shown numerically. PMID- 20588615 TI - Magnetic field modulation of intense surface plasmon polaritons. AB - We present correlated experimental and theoretical studies on the magnetic field modulation of Surface Plasmon Polaritons (SPPs) in Au/Co/Au trilayers. The trilayers were grown by sputter deposition on glass slides with the Co films placed at different distances from the surface and with different thickness. We show that it is possible to tailor Au/Co/Au trilayers with the critical thickness needed for optimum excitation of SPPs leading to large localized electromagnetic fields. The modification of the SPP wave vector by externally applied magnetic fields was investigated by measuring the magneto-optical activity in transverse configuration. In addition, using magneto-optics as a tool we determined the spatial distribution of the SPP generated electromagnetic fields within Au/Co/Au samples by analyzing the field-dependent optical response, demonstrating that it is possible to excite SPPs that exhibit large electromagnetic fields that are also magneto-optically active and therefore can be modulated by externally applied magnetic fields. PMID- 20588616 TI - Real time optical method for localization of inclusions embedded in turbid media. AB - A simple and fast time-domain method for localizing inclusions, fluorescent optical probes or absorbers, is presented. The method offers new possibilities for situations where complete tomographic measurements are not permitted by the examined object, for example in endoscopic examination of the human prostate or the oesophagus. Feasibility has been envisioned with a phantom study conducted on a point-like fluorochrome embedded in a diffusing medium mimicking the optical properties of biological tissues. PMID- 20588617 TI - Suspended optical fiber-to-waveguide mode size converter for silicon photonics. AB - In this paper, an efficient and novel optical fiber-to-waveguide mode size converter for Si Photonics devices with sub-micron waveguides is developed on the SOI platform. This optical converter is composed of a suspended SiO(2) waveguide and overlapped Si nano-tapers located in the center of suspended SiO(2) waveguide. Laterally connected SiO(2) beams provide structural support for the suspended SiO(2) waveguide. The optical input signal from the optical fiber is launched into the suspended SiO(2) waveguide, and then coupled into the Si nano taper. The measured coupling loss using a lensed fiber with 5 microm spot diameter is 1.7 ~2.0 dB/facet for TE mode and 2.0 ~2.4 dB/facet for TM mode in the wavelength range of 1520 ~1600 nm. When a cleaved fiber with 9.2microm spot diameter is used, the coupling losses for both TE and TM modes are less than 4.0 dB/facet at 1550 nm. For the case of lensed fiber, the alignment tolerances for both TE and TM modes are about +/- 1.7 microm for 1 dB excess loss in both X and Y axes. The alignment tolerances for both modes of TE and TM are relaxed, exceeding +/- 2.5 microm for 1 dB excess loss in both X and Y axes when a cleaved fiber is used. PMID- 20588618 TI - Optical signal processing on a silicon chip at 640Gb/s using slow-light. AB - We demonstrate optical performance monitoring of in-band optical signal to noise ratio (OSNR) and residual dispersion, at bit rates of 40Gb/s, 160Gb/s and 640Gb/s, using slow-light enhanced optical third harmonic generation (THG) in a compact (80microm) dispersion engineered 2D silicon photonic crystal waveguide. We show that there is no intrinsic degradation in the enhancement of the signal processing at 640Gb/s relative to that at 40Gb/s, and that this device should operate well above 1Tb/s. This work represents a record 16-fold increase in processing speed for a silicon device, and opens the door for slow light to play a key role in ultra-high bandwidth telecommunications systems. PMID- 20588619 TI - Numerical study on heterodyne terahertz detection in field effect transistor. AB - Numerical method on the heterodyne terahertz detection characteristics of field effect characteristics of field effect transistors is studied in this paper which is based on the hydrodynamic equations which govern the terahertz signal transport in field effect transistors (FETs). A modification is made in an existed numerical tool established by our group by coupling the heterodyne characteristics. This modified numerical tool work well in all operation regions of FETs from sub-threshold to strong inversion and from linear to saturation. And the results are used to demonstrate the potential for using MOS transistors as THz detectors and investigate the optimization of the device structure. PMID- 20588620 TI - SPM mitigation in 16-ary amplitude-and-differential-phase shift keying long-haul optical transmission systems. AB - We report a self-phase-modulation (SPM) mitigation method in the electrical domain for 16-level amplitude-and-differential-phase-shift keying (16-ADPSK) signals. The method helps to increases the transmission distance of 60 Gbit/s/channel 16-ADPSK systems by around 1.5 times. PMID- 20588621 TI - A higher-order-mode fiber delivery for Ti:Sapphire femtosecond lasers. AB - We report the first higher-order-mode fiber with anomalous dispersion at 800nm and demonstrate its potential in femtosecond pulse delivery for Ti:Sapphire femtosecond lasers. We obtain 125fs pulses after propagating a distance of 3.6 meters in solid-silica fiber. The pulses could be further compressed in a quartz rod to nearly chirp-free 110fs pulses. Femtosecond pulse delivery is achieved by launching the laser output directly into the delivery fiber without any pre chirping of the input pulse. The demonstrated pulse delivery scheme suggests scaling to >20meters for pulse delivery in harsh environments not suited for oscillator operation or in applications that require long distance flexibility. PMID- 20588622 TI - Micropipe flow visualization using digital in-line holographic microscopy. AB - Digital in-line holography is used to visualize particle motion within a cylindrical micropipe. Analytical expression of the intensity distribution recorded in the CCD sensor plane is derived using the generalized Huygens-Fresnel integral associated with the ABCD matrices formalism. Holograms obtained in a 100microm in diameter micropipe are then reconstructed using fractional Fourier transformation. Astigmatism brought by the cylindrical micropipe is finally used to select a three dimensional region of interest in the microflow and thus to improve axial localization of objects located within a micropipe. Experimental results are presented and a short movie showing particle motion within a micropipe is given. PMID- 20588623 TI - Focal modulation using rotating phase filters. AB - We describe a simple method of refocusing optical systems that is based on the use of two identical phase filters. These filters are divided in annuli and each annulus is divided into sectors with a particular phase value. A controlled focus displacement is achieved by rotating one filter with respect to the other. This displacement is related with the filter parameters. Transverse responses are studied as a function of filters relative position. Furthermore, the experimental set up shows that theoretical prediction fit well with experimental results. The main advantage of this system is the ease of fabrication so that it could be useful in different applications requiring small size, light weight or thin systems, like mobile phone cameras, microscopy tomography, and others. PMID- 20588624 TI - An encryption method with multiple encrypted keys based on interference principle. AB - An encryption and verification method with multiple encrypted keys based on interference principle is proposed. The encryption process is realized on computer digitally and the verification process can be completed optically or digitally. Two different images are encoded into three diffractive phase elements (DPEs) by using two different incident wavelengths. Three DPEs have different distances from output plane. The two wavelength parameters and three distance parameters can be used as encryption keys, which will boost security degree of this system. Numerical simulation proves that the proposed encryption method is valid and has high secrecy level. PMID- 20588626 TI - Second harmonic generation in periodically polarity-inverted zinc oxide. AB - We report on the second harmonic generation (SHG) in 2D periodically polarity inverted (PPI) ZnO heterostructures. The grating structures with nanometer-scale periodicity are fabricated on (0001) Al(2)O(3) substrates by using the in situ polarity inversion method. The achievements of SHG with grating in fabricated PPI ZnO structures are demonstrated under consideration of quasi phase matching conditions. In general, grating formation using the this periodical array of differnet polar surface can be extended to the other heteroepitaxial systems with polarity characteristics. PMID- 20588625 TI - Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system. AB - In this work, a first-of-its-kind fully integrated tri-modality system that combines fluorescence, diffuse optical and x-ray tomography (FT/DOT/XCT) into the same setting is presented. The purpose of this system is to perform quantitative fluorescence tomography using multi-modality imaging approach. XCT anatomical information is used as structural priori while optical background heterogeneity information obtained by DOT measurements is used as functional priori. The performance of the hybrid system is evaluated using multi-modality phantoms. In particular, we show that a 2.4 mm diameter fluorescence inclusion located in a heterogeneous medium can be localized accurately with the functional a priori information, although the fluorophore concentration is recovered with 70% error. On the other hand, the fluorophore concentration can be accurately recovered within 8% error only when both DOT optical background functional and XCT structural a priori information are utilized to guide and constrain the FT reconstruction algorithm. PMID- 20588627 TI - Multiphoton excitation characteristics of cellular fluorophores of human skin in vivo. AB - In vivo multiphoton tomography with a wavelength-tunable femtosecond laser has been performed to investigate the autofluorescence intensity of major endogenous fluorophores of human skin in dependence on the excitation wavelength. In high resolution multiphoton images of different skin layers, clear trends were found for fluorophores like keratin, NAD(P)H, melanin as well as for the elastin and collagen networks. The analysis of the measurements is supplemented by additional measurements of fluorescence lifetime imaging and signal-decay curves by time correlated single-photon counting. PMID- 20588628 TI - Optomechanical zipper cavity lasers: theoretical analysis of tuning range and stability. AB - The design of highly wavelength tunable semiconductor laser structures is presented. The system is based on a one dimensional photonic crystal cavity consisting of two patterned, doubly-clamped nanobeams, otherwise known as a "zipper" cavity. Zipper cavities are highly dispersive with respect to the gap between nanobeams in which extremely strong radiation pressure forces exist. Schemes for controlling the zipper cavity wavelength both optically and electrically are presented. Tuning ranges as high as 75 nm are achieved for a nominal design wavelength of lambda = 1.3 microm. Sensitivity of the mechanically compliant laser structure to thermal noise is considered, and it is found that dynamic back-action of radiation pressure in the form of an optical or electrical spring can be used to stabilize the laser frequency. Fabrication of zipper cavity laser structures in GaAs material with embedded self-assembled InAs quantum dots is presented, along with measurements of photoluminescence spectroscopy of the zipper cavity modes. PMID- 20588629 TI - Diffraction-enhanced beam-focusing for X-rays in curved multi-plate crystal cavity. AB - Unusual x-ray focusing effect is reported for parabolic curved multi-plate x-ray crystal cavities of silicon consisting of compound refractive lenses (CRL). The transmitted beam of the (12 4 0) back reflection near 14.4388 keV from these monolithic silicon crystal devices exhibits extraordinary focusing enhancement, such that the focal length is reduced by as much as 18% for 2-beam and 56% for 24 beam diffraction from the curved crystal cavity. This effect is attributed to the presence of the involved Bragg diffractions, in which the wavevector of the transmitted beam is bent further when traversing several curved crystal surfaces. PMID- 20588630 TI - Multiple extraordinary optical transmission peaks from evanescent coupling in perforated metal plates surrounded by dielectrics. AB - We study numerically and theoretically the optical transmission of nanostructured gold films embedded in dielectric claddings. We show how multiple transmission peaks appear as the claddings thickness increases. These transmission peaks come not only from surface plasmon polariton excitations but also from the excitation of Fabry-Perot modes sustained at the claddings, coupled through the metal, as long as a periodic pattern is milled in the metal film. We propose that this structure could be used as an ultracompact all-optical switch by surrounding the metal film with Kerr nonlinear dielectric layers. PMID- 20588631 TI - Direct calibration of a spatial light modulator by lateral shearing interferometry. AB - A new interferometric technique is described to measure the complex modulation curve of a spatial light modulator. Based on a lateral shear imaging interferometer, it enables the amplitude and phase modulation for several modulation levels to be displayed simultaneously in a single interferogram. As an example of the power of this technique a heuristic optimization of input and output elliptical polarization states for a mostly-phase operation mode was obtained within a few minutes for a commercial twisted-nematic liquid crystal display. PMID- 20588632 TI - Laser-induced breakdown spectroscopy of copper with a 2 microm thulium fiber laser. AB - We report the first implementation of a 2 microm thulium fiber laser in a Laser Induced Breakdown Spectroscopy system. Emission from plasma on copper samples was analyzed from 200 to 900 nm. The low ablation fluence (<100 J.cm(-2)) and 200 ns pulse duration lead to a plasma with neither continuum emission, nor air emission in the near-infrared region. PMID- 20588633 TI - High gain broadband amplification of ultraviolet pulses in optical parametric chirped pulse amplifier. AB - We report on a high gain amplification of broadband ultraviolet femtosecond pulses in an optical parametric chirped pulse amplifier. Broadband ultraviolet seed pulses were obtained by an achromatic frequency doubling of the output from a femtosecond Ti:Sapphire oscillator. Stretched seed pulses were amplified in a multipass parametric amplifier with a single BBO crystal pumped by a ns frequency quadrupled Nd:YAG laser. A noncollinear configuration was used for a broadband amplification. The total (after compression) amplification of 2.510(5) was achieved, with compressed pulse energy of 30 microJ and pulse duration of 24 fs. We found that the measured gain was limited by thermal effects induced by the absorption of the pump laser by color centers created in the BBO crystal. PMID- 20588634 TI - Photonic crystal fiber based Mach-Zehnder interferometer for DPSK signal demodulation. AB - We demonstrate a novel fiber-based in-line DPSK demodulator using an in-fiber Mach-Zehnder interferometer (MZI). The device is fabricated by mismatch splicing of a photonic crystal fiber (PCF) with standard single mode fibers. The spectral characteristics at different PCF lengths are analyzed. The envelope of the interference fringes show a period that is inversely proportional to the PCF length, and is attributed to the periodic coupling between the core mode and the cladding mode. Error free demodulations of 10-Gb/s RZ- and NRZ-DPSK signals have been demonstrated using the in-fiber PCF-MZI demodulator with only 3-m PCF to introduce 91-ps delay. Wideband DPSK demodulation has also been achieved. PMID- 20588635 TI - 106.5 W high beam quality diode-side-pumped Nd:YAG laser at 1123 nm. AB - We demonstrate a diode-side-pumped continuous wave (CW) Nd:YAG laser at 1123 nm with over 100 W's output power and good beam quality. The resonator adopts convex convex structure working in a thermally near unstable cavity. By precise coating design a single 1123 nm wavelength is delivered. Under the pumped power of 870 W, an output power of 106.5 W is obtained, corresponding to an optical-optical conversion efficiency of 12.2%. The beam quality of M(2) factor is measured to be 5.6. To the best of our knowledge, this is the highest output power with good beam quality for 1123 nm CW Nd:YAG laser. PMID- 20588636 TI - Sensitivity of coherent dual-comb spectroscopy. AB - Coherent dual comb spectroscopy can provide high-resolution, high-accuracy measurements of a sample response in both magnitude and phase. We discuss the achievable signal-to-noise ratio (SNR) due to both additive white noise and multiplicative noise, and the corresponding sensitivity limit for trace gas detection. We show that sequential acquisition of the overall spectrum through a tunable filter, or parallel acquisition of the overall spectrum through a detector array, can significantly improve the SNR under some circumstances. We identify a useful figure of merit as the quality factor, equal to the product of the SNR, normalized by the square root of the acquisition time, and the number of resolved frequency elements. For a single detector and fiber-laser based system, this quality factor is 10(6) - 10(7) Hz(1/2). PMID- 20588637 TI - Tuning quantum-dot based photonic devices with liquid crystals. AB - Microdisks made from GaAs with embedded InAs quantum dots are immersed in the liquid crystal 4-cyano-4'-pentylbiphenyl (5CB). The quantum dots serve as emitters feeding the optical modes of the photonic cavity. By changing temperature, the liquid crystal undergoes a phase transition from the isotropic to the nematic state, which can be used as an effective tuning mechanism of the photonic modes of the cavity. In the nematic state, the uniaxial electrical anisotropy of the liquid crystal molecules can be exploited for orienting the material in an electric field, thus externally controlling the birefringence of the material. Using this effect, an electric field induced tuning of the modes is achieved. Numerical simulations using the finite-differences time-domain (FDTD) technique employing an anisotropic dielectric medium allow to understand the alignment of the liquid crystal molecules on the surface of the microdisk resonator. PMID- 20588638 TI - Microwave optical double resonance spectroscopy of ammonia in a hollow-core fiber. AB - We have demonstrated microwave optical double resonance spectroscopy of the nu(1) + nu(3) and nu(1) + 2nu(4) bands of ammonia in a hollow-core photonic bandgap fiber. Signal strength and lineshapes are analyzed. Spectroscopic assignments of previously assigned lines and previously proposed assignments have been confirmed and new assignments have been made. Several microwave transitions in the excited vibrational states have been measured for the first time. PMID- 20588639 TI - Angular momentum decomposition of nonparaxial light beams. AB - The total angular momentum per unit length of a general non-paraxial beam is decomposed into an orbital component associated with the spiral spectrum at the far field and a component concerning the balance between right- and left-handed circular-polarization content of the angular spectrum. Expressions for the linear momentum and energy per unit length are also provided. The well-known division into orbital and spin components is shown to be recovered in the paraxial limit. PMID- 20588640 TI - Observation of photorefractive simultons in lithium niobate. AB - Spatial and temporal locking of fundamental and second harmonic pulses was realized by means of photorefractive nonlinearity and highly mismatched harmonic generation. Due to the presence of both phase-locked and unlocked second harmonic pulses, a twin simultonic state was observed. Simultonic filamentation occurring at high pumping rates allowed us to determine a relation between the simulton's waist and its intensity. PMID- 20588641 TI - Effects of the equivalent coupling layer on ultra-long-range surface-plasmon polariton waves. AB - The mechanism and design of p- and s- polarized ultra-long-range surface-plasmon polariton (SPP) propagation in the configuration {prism/ equivalent coupling layer (ECL)/ silver film (20 nm)/ equivalent substrate (ES)} are investigated using a normalized admittance diagram (NAD). The excitation of ultra-long-range SPP waves is characterized as a huge open loop of the NAD of the metal film at a designated angle of incidence. We propose three kinds of ECLs to complete the multilayer ultra-long-range SPP design: the normalized admittance of the ECL is (i) real (ii) infinite (iii) imaginary. The ultra-long propagation lengths in the three designs are compared at a wavelength of 632.8 nm for p- and s-polarization states. PMID- 20588642 TI - High speed carrier-depletion modulators with 1.4V-cm V(pi)L integrated on 0.25microm silicon-on-insulator waveguides. AB - We demonstrate a very efficient high speed silicon modulator with an ultralow pi phase-shift voltage-length product V(pi)L = 1.4V-cm. The device is based on a Mach-Zehnder interferometer (MZI) fabricated using 0.25microm thick silicon-on insulator (SOI) waveguide with offset lateral PN junctions. Optimal carrier depletion induced index change has been achieved through the optimization of the overlap region of carriers and photons. The 3dB bandwidth of a typical 1mm long device was measured to be more than 12GHz. An eye-diagram taken at a transmission rate of 12.5Gb/s confirms the high speed capability of the device. PMID- 20588643 TI - Towards local motion detection by the use of analog self electro-optic effect device. AB - We demonstrated the use of the analog self electro-optic effect device (SEED) as part of an artificial retina chip for the detection and estimation of local motion. The characterization was performed by comparing our chip to biological and computational models and to other artificial retina chips. Its main unique feature is the optical output, since most chips have electrical output. By combining the response of the chip with temporal information about the input image, it is possible to estimate the velocity perpendicular to an edge, including its direction. PMID- 20588644 TI - Grating couplers for broadside input and output coupling of long-range surface plasmons. AB - Metal gratings for in-coupling a Gaussian beam incident from broadside to the long-range surface plasmon polariton (LRSPP) propagating in one direction along a membrane-supported Au slab bounded by air or water are proposed and modeled by the finite-difference time-domain method. Grating couplers for out-coupling the propagating LRSPP into free radiation directed along broadside are also investigated. Short grating designs consisting of a small number of Au bumps yield 15% to 20% in-coupling efficiencies, and about 60% out-coupling efficiencies. LRSPP back-reflections along the membrane waveguide caused by the out-coupling grating are also calculated and discussed. PMID- 20588645 TI - Patterning of two-dimensional planar lithium niobate architectures on glass surface by laser scanning. AB - Two-dimensional planar LiNbO(3) (LN) crystal architectures are patterned on the surface of Li(2)O-Nb(2)O(5)-B(2)O(3)-SiO(2) glass by continuous wave ytterbium YVO(4) fiber laser (wavelength: 1080 nm) irradiations, in which lasers are scanned continuously with narrow steps (pitches: 0.3 and 0.5 microm) and thus with overlaps of laser irradiated parts. For the planar LN crystals (area: 50 microm x 100 microm) patterned by laser scanning with a power of 0.9 W and a speed of 7 microm/s, it is demonstrated from polarized micro-Raman scattering spectra and azimuthal dependence of second harmonic intensities that the c-axis orientation of LN crystals is established along the laser scanning direction. The present study proposes that the laser irradiation technique gives us uniform LN crystal films on the glass surface. PMID- 20588646 TI - Fabrication of micro DOE using micro tools shaped with focused ion beam. AB - A novel method is proposed to fabricate micro Diffractive Optical Elements (DOE) using micro cutting tools shaped with focused ion beam (FIB) milling. Micro tools with nanometric cutting edges and complicated shapes are fabricated by controlling the tool facet's orientation relative to the FIB. The tool edge radius of less than 30 nm is achieved for the nano removal of the work materials. Semi-circular micro tools and DOE-shaped micro tools are developed to fabricate micro-DOE and sinusoidal modulation templates. Experiments show that the proposed method can be a high efficient way in fabricating micro-DOE with nanoscale surface finishes. PMID- 20588647 TI - Frequency doubling of low power images using a self-imaging cavity. AB - A self-imaging resonator can be simultaneously resonant for many transverse modes and therefore allows cavity build-up for images of various shapes. The stability properties of such a cavity are reviewed. We have used this device for the first time to enhance the efficiency of second harmonic generation of weak images. We characterize the global and local efficiency of the second harmonic generation, and discuss its limitation due to the spatial bandwidth of the cavity and the diffraction along the crystal length. PMID- 20588648 TI - Broadband THz lasing from a photon-phonon quantum cascade structure. AB - Laser emission over a broad range of frequencies from 2.8 to 4.1 THz is reported for a two-quantum well, photon-phonon cascade structure. Maximum operating temperatures of 125 K are reported, with optical peak powers in eccess of 30 mW from a double-metal ridge waveguide. The broadband nature of the gain curve is identified as due to coherent coupling of the injector and upper lasing states. Internal quantum efficiencies reaching 43 % are evaluated at 10 K.The laser operates in both polarities, showing laser action in reverse bias up to a temperature of 90 K. Simulations based on a full treatment of the structure with density matrix formalism are also presented and discussed. PMID- 20588649 TI - "Slow Light" in stimulated Brillouin scattering: on the influence of the spectral width of pump radiation on the group index: Comment. AB - In a recent paper by Kovalev et al [Optics Express 17, 17317 (2009)] the coupled equations describing stimulated Brillouin scattering (SBS) were solved in the Fourier domain. The main conclusion driven by the authors was that SBS pump spectral broadening was not effective in increasing the interaction bandwidth. While the calculations are essentially correct, the interpretation of the results leads to erroneous conclusions. PMID- 20588650 TI - "Slow Light" in stimulated Brillouin scattering: on the influence of the spectral width of pump radiation on the group index: Reply. AB - We show that the claims in the Comment are misleading and in instances contradictory. PMID- 20588652 TI - Influence of pointing fluctuation on intense laser beams propagation in plasma channels. AB - An off-axis incident model is presented to analyze the influence of beam pointing fluctuation on the propagation properties of intense laser beams in plasma channels. The equations for the beam spot size and centroid are obtained by applying the variational method. The beam pointing fluctuation contributes additional focusing effect by amplifying relativistic self-focusing, leading to periodically modified oscillations of the spot size. The beam centroid oscillates along the channel axis with the amplitude close to its initial off-axis displacement, while the oscillation frequency is scaled as the square of the dimensionless channel strength parameter. PMID- 20588651 TI - Performance metrics of an optical spectral imaging system for intra-operative assessment of breast tumor margins. AB - As many as 20-70% of patients undergoing breast conserving surgery require repeat surgeries due to a close or positive surgical margin diagnosed post-operatively [1]. Currently there are no widely accepted tools for intra-operative margin assessment which is a significant unmet clinical need. Our group has developed a first-generation optical visible spectral imaging platform to image the molecular composition of breast tumor margins and has tested it clinically in 48 patients in a previously published study [2]. The goal of this paper is to report on the performance metrics of the system and compare it to clinical criteria for intra operative tumor margin assessment. The system was found to have an average signal to noise ratio (SNR) >100 and <15% error in the extraction of optical properties indicating that there is sufficient SNR to leverage the differences in optical properties between negative and close/positive margins. The probe had a sensing depth of 0.5-2.2 mm over the wavelength range of 450-600 nm which is consistent with the pathologic criterion for clear margins of 0-2 mm. There was <1% cross talk between adjacent channels of the multi-channel probe which shows that multiple sites can be measured simultaneously with negligible cross-talk between adjacent sites. Lastly, the system and measurement procedure were found to be reproducible when evaluated with repeated measures, with a low coefficient of variation (<0.11). The only aspect of the system not optimized for intra operative use was the imaging time. The manuscript includes a discussion of how the speed of the system can be improved to work within the time constraints of an intra-operative setting. PMID- 20588653 TI - Experimental determination of the sensitivity of Bloch surface waves based sensors. AB - Detection of glucose in water solution for several different concentrations has been performed with the purpose to determine the sensitivity of Near Infrared Bloch Surface Waves (lambda = 1.55microm) upon refractive index variations of the outer medium. TE-polarized electromagnetic surface waves are excited by a prism on a silicon nitride multilayer, according to the Kretschmann configuration. The real-time reflectance changes induced by discrete variations in glucose concentration has been revealed and analyzed. Without using any particular averaging strategy during the measurements, we pushed the device detection limit down to a glucose concentration of 2.5mg/dL, corresponding to a minimum detectable refractive index variation of the water solution as low as 3.8.10(-6). PMID- 20588654 TI - Multi-pass Shack-Hartmann planeness test: monitoring thermal stress. AB - The multi-pass solution for surface measurements with the help of a Shack Hartmann sensor (SHS) on the basis of a Fizeau cavity enables fast access to surface deviation data due to the high speed of the SHS and easy referencing of the measured data through difference measurements. The multi-pass solution described in a previous publication [J. Schwider, Opt. Express 16, 362 (2008)], provides highly sensitive measurements of small displacements caused by thermal non-equilibrium states of the test set up. Here, we want to demonstrate how a pulsed thermal load changes the surface geometry. In addition the temporal response for different plate materials is monitored through a fast wave front measurement with very high sensitivity. The thermal load close to a delta function in time will be applied from the back-side of a plane plate by heating a small Peltier element with a heat impulse of known order of magnitude. The development of the surface deviation on the time axis can be monitored by storing a set of successive deviation pictures. PMID- 20588655 TI - Sub-shot-noise-limit discrimination of on-off keyed coherent signals via a quantum receiver with a superconducting transition edge sensor. AB - We demonstrate a sub-shot-noise-limit discrimination of on-off keyed coherent signals by an optimal displacement quantum receiver in which a superconducting transition edge sensor is installed. Use of a transition edge sensor and a fiber beam splitter realizes high total detection efficiency and high interference visibility of the receiver and the observed average error surpasses the shot noise-limit in a wider range of the signal power. Our technique opens up a new technology for the sub-shot-noise-limit detection of coherent signals in optical communication channels. PMID- 20588656 TI - On the photonic implementation of universal quantum gates, bell states preparation circuit and quantum LDPC encoders and decoders based on directional couplers and HNLF. AB - The Bell states preparation circuit is a basic circuit required in quantum teleportation. We describe how to implement it in all-fiber technology. The basic building blocks for its implementation are directional couplers and highly nonlinear optical fiber (HNLF). Because the quantum information processing is based on delicate superposition states, it is sensitive to quantum errors. In order to enable fault-tolerant quantum computing the use of quantum error correction is unavoidable. We show how to implement in all-fiber technology encoders and decoders for sparse-graph quantum codes, and provide an illustrative example to demonstrate this implementation. We also show that arbitrary set of universal quantum gates can be implemented based on directional couplers and HNLFs. PMID- 20588657 TI - Ultrashort-pulse laser with an intracavity phase shaping element. AB - A novel ultrashort-pulse laser cavity configuration that incorporates an intracavity deformable mirror as a phase control element is reported. A user defined spectral phase relation of 0.7 radians relative shift could be produced at around 1035 nm. Phase shaping as well as pulse duration optimization was achieved via a computer-controlled feedback loop. PMID- 20588658 TI - Application of spectrum differential integration method in an in-line fiber Mach Zehnder refractive index sensor. AB - A novel spectrum differential integration (SDI) method has been proposed and verified in an in-line fiber Mach-Zehnder (MZ) refractive index (RI) sensor using salt solutions. In SDI method, the difference between two interference spectra is determined by pointwise subtraction at each wavelength, followed by integration of the absolute differences along the scan range. Compared with the widely used peak wavelength shift method, the SDI method is more reliable over a wide wavelength range (on the order of 400 nm) and results in higher sensitivity as well as reduced device-dependence. The SDI method can also be utilized with other kinds of modal interferometric sensors. PMID- 20588659 TI - High-Q design of semiconductor-based ultrasmall photonic crystal nanocavity. AB - We report a high-Q design for a semiconductor-based two-dimensional zero-cell photonic crystal (PhC) nanocavity with a small mode volume. The optimization of displacements of hexagonal-lattice air holes in the Gamma-M direction, in addition to the Gamma-K direction, resulted in a cavity quality factor Q of 2.8 x 10(5) sustaining the small modal volume of 0.23(lambda(0)/n)(3). The momentum space consideration of out-of-plane radiation loss showed that the optimization of air hole displacements in both the in-plane x and y directions reduced FT components in the leaky region along the k(x) and k(y) axes, respectively. This high-Q cavity design is applicable to Si and GaAs semiconductor materials. PMID- 20588660 TI - RECIST versus volume measurement in medical CT using ellipsoids of known size. AB - Two hundred eighty three uniaxial ellipsoids with sizes from 4 mm to 11 mm were measured with a coordinate measuring matching (CMM) and also scanned using a medical computed tomography (CT) machine. Their volumes were determined by counting voxels over a threshold, as well as using equivalent volumes from the length given by the RECIST 1.1 criterion (Response Evaluation Criteria in Solid Tumors). The volumetric measurements yield an order of magnitude reduction in residuals compared to the CMM measurements than the residuals of the RECIST measurements also compared to the CMM measurements. PMID- 20588661 TI - Simultaneous imaging of oxygen tension and blood flow in animals using a digital micromirror device. AB - In this study we present a novel imaging method that combines high resolution cerebral blood flow imaging with a highly flexible map of absolute pO(2). In vivo measurements of pO(2) in animals using phosphorescence quenching is a well established method, and is preferable over electrical probes which are inherently invasive and are limited to single point measurements. However, spatially resolved pO(2) measurements using phosphorescence lifetime quenching typically require expensive cameras to obtain images of pO(2) and often suffer from poor signal to noise. Our approach enables us to retain the high temporal resolution and sensitivity of single point detection of phosphorescence by using a digital micromirror device (DMD) to selectively illuminate arbitrarily shaped regions of tissue. In addition, by simultaneously using Laser Speckle Contrast Imaging (LSCI) to measure relative blood flow, we can better examine the relationship between blood flow and absolute pO(2). We successfully used this instrument to study changes that occur during ischemic conditions in the brain with enough spatial resolution to clearly distinguish different regions. This novel instrument will provide researchers with an inexpensive and improved technique to examine multiple hemodynamic parameters simultaneously in the brain as well as other tissues. PMID- 20588662 TI - Continuum fusion: a theory of inference, with applications to hyperspectral detection. AB - A new theoretical framework is created for the class of detection problems traditionally addressed by the generalized likelihood ratio test. Absent prior knowledge that would permit implementation of the optimal detector, a family of optimal detectors is fused according to any one of a group of criteria. Geometrical solutions are presented to several specific problems motivated by hyperspectral signal processing. For the general case, a set of partial differential relations is derived. The generalized likelihood ratio test is shown to be equivalent to one of several flavors of continuum fusion detector. PMID- 20588663 TI - Hong-Ou-Mandel dip measurements of polarization-entangled photon pairs at 1550 nm. AB - We performed a quantum interference experiment using two polarization-entangled photon pairs at 1550 nm, created in periodically poled lithium niobate waveguides. Using four-fold coincidences, a Hong-Ou-Mandel dip at diagonal polarization was observed with a visibility of 74.5% before subtracting accidental coincidences. This experiment lays a foundation for demonstrating polarization-based entanglement swapping and for realizing a quantum relay. PMID- 20588664 TI - High color rendering white light-emitting-diode illuminator using the red emitting Eu(2+)-activated CaZnOS phosphors excited by blue LED. AB - A red phosphor CaZnOS:Eu(2+) was synthesized by solid state reaction and has been evaluated as a candidate for white LEDs. For this material, the XRD, PL, PL excitation (PLE) and diffuse reflection spectra have also been investigated. CaZnOS:Eu(2+) reveals a broad absorption band and good color purity. By utilizing a mixture of red-emitting CaZnOS:Eu(2+), green-emitting (Ba,Sr)(2)SiO(4):Eu(2+) and yellow-emitting Y(3)Al(5)O(12):Ce(3+) as light converters, an intense white InGaN-based blue-LED (~460 nm) was fabricated to exhibit a high color-rendering index Ra of 85 at a correlated color temperature of 4870 K. Based on the results, we are currently evaluating the potential application of CaZnOS:Eu(2+) as a red emitting blue-chip convertible phosphor. PMID- 20588665 TI - Integrated optical frequency-resolved Mach-Zehnder interferometers for label-free affinity sensing. AB - Integrated Optical Frequency-Resolved Mach-Zehnder Interferometry (IO FR-MZI) is introduced as an alternative, cost-efficient operation principle for integrated optical label-free affinity sensors that can combine high sensitivity with high versatility in terms of potential applications and experimental configurations. A detailed theoretical analysis of the method is presented followed by a semi analytical approximation and numerical calculations in order to quantify the sensitivity and limits of detection of the FR-MZI over Single Wavelength MZI. The obtained results substantiate that IO FR-MZI- based sensors constitute a generic technological platform of high sensitivity that can be implemented into a plethora of detection schemes. For an optimized optical design well below 1mm in length the limit of detection can be as low as 0.025A in terms of adlayer effective thickness allowing for truly miniaturized integrated optical sensors fabricated with high yield with standard microfabrication techniques. PMID- 20588666 TI - Image artifacts in hybrid imaging systems with a cubic phase mask. AB - We present the first analytical analysis of image artifacts in defocused hybrid imaging systems that employ a cubic phase-modulation function. We show that defocus artifacts have the form of image replications and are caused by a net phase modulation of the optical transfer function. Both numerical simulations and experimental images are presented that exhibit replication artifacts that are compatible with the analytical expressions. PMID- 20588667 TI - Inline holographic coherent anti-Stokes Raman microscopy. AB - We demonstrate a simple approach for inline holographic coherent anti-Stokes Raman scattering (CARS) microscopy, in which a layer of uniform nonlinear medium is placed in front of a specimen to be imaged. The reference wave created by four wave mixing in the nonlinear medium can interfere with the CARS signal generated in the specimen to result in an inline hologram. We experimentally and theoretically investigate the inline CARS holography and show that it has chemical selectivity and can allow for three-dimensional imaging. PMID- 20588668 TI - Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds. AB - In this paper, we demonstrate for the first time that the detailed cutaneous blood flow at capillary level within dermis of human skin can be imaged by optical micro-angiography (OMAG) technique. A novel scanning protocol, i.e. fast B scan mode is used to achieve the capillary flow imaging. We employ a 1310nm system to scan the skin tissue at an imaging rate of 300 frames per second, which requires only ~5 sec to complete one 3D imaging of capillary blood flow within skin. The technique is sensitive enough to image the very slow blood flows at ~4 microm/sec. The promising results show a great potential of OMAG's role in the diagnosis, treatment and management of human skin diseases. PMID- 20588669 TI - Electrically tunable Yb-doped fiber laser based on a liquid crystal photonic bandgap fiber device. AB - We demonstrate electrical tunability of a fiber laser using a liquid crystal photonic bandgap fiber. Tuning of the laser is achieved by combining the wavelength filtering effect of a tunable liquid crystal photonic bandgap fiber device with an ytterbium-doped photonic crystal fiber. We fabricate an all spliced laser cavity based on the liquid crystal photonic bandgap fiber mounted on a silicon assembly, a pump/signal combiner with single-mode signal feed through and an ytterbium-doped photonic crystal fiber. The laser cavity produces a single-mode output and is tuned in the range 1040-1065 nm by applying an electric field to the silicon assembly. PMID- 20588670 TI - Linearization of the response of a 91-actuator magnetic liquid deformable mirror. AB - We present the experimental performance of a 91-actuator deformable mirror made of a magnetic liquid (ferrofluid) using a new technique that linearizes the response of the mirror by superposing a uniform magnetic field to the one produced by the actuators. We demonstrate linear driving of the mirror using influence functions, measured with a Fizeau interferometer, by producing the first 36 Zernikes polynomials. Based on our measurements, we predict achievable mean PV wavefront amplitudes of up to 30 microm having RMS residuals of lambda/10 at 632.8 nm. Linear combination of Zernikes and over-time repeatability are also demonstrated. PMID- 20588671 TI - Near-diffraction-limited annular flattop beam shaping with dual phase only liquid crystal spatial light modulators. AB - We demonstrate the annular flattop beam shaping technique with dual phase only liquid crystal spatial light modulators (LC-SLM) based on the refractive laser beam shaping systems. One LC-SLM redistributes the intensity distribution, and the other restores the initial underlying wave front. Differing from the conventional annular beam shaping technique, the wave front of the output beam can be maintained. The influences of deviations of beam waist and beam shape on the output beam profile are discussed in detail. Experimental results show that approximate 71% of the power is enclosed in a region with less than 7% rms intensity variation. The 4.1mm diameter near-diffraction-limited beam retains an annular flattop intensity distribution without significant diffraction peaks for a working distance of more than 24cm in the near field. PMID- 20588672 TI - A fourth-order Runge-Kutta in the interaction picture method for numerically solving the coupled nonlinear Schrodinger equation. AB - A fourth-order Runge-Kutta in the interaction picture (RK4IP) method is presented for solving the coupled nonlinear Schr odinger equation (CNLSE) that governs the light propagation in optical fibers with randomly varying birefringence. The computational error of RK4IP is caused by the fourth-order Runge-Kutta algorithm, better than the split-step approximation limited by the step size. As a result, the step size of RK4IP can have the same order of magnitude as the dispersion length and/or the nonlinear length of the fiber, provided the birefringence effect is small. For communication fibers with random birefringence, the step size of RK4IP can be orders of magnitude larger than the correlation length and the beating length of the fibers, depending on the interaction between linear and nonlinear effects. Our approach can be applied to the fibers having the general form of local birefringence and treat the Kerr nonlinearity without approximation. Our RK4IP results agree well with those obtained from Manakov-PMD approximation, provided the polarization state can be mixed enough on the Poincar e sphere. PMID- 20588673 TI - Photonic crystal spectrometer. AB - We demonstrate a new kind of optical spectrometer employing photonic crystal patterns to outcouple waveguided light from a transparent substrate. This spectrometer consists of an array of photonic crystal patterns, nanofabricated in a polymer on a glass substrate, combined with a camera. The camera captures an image of the light outcoupled from the patterned substrate; the array of patterns produces a spatially resolved map of intensities for different wavelength bands. The intensity map of the image is converted into a spectrum using the photonic crystal pattern response functions. We present a proof of concept by characterizing a white LED with our photonic crystal spectrometer. PMID- 20588674 TI - Linearly polarized second harmonic generation microscopy reveals chirality. AB - In optics, chirality is typically associated with circularly polarized light. Here we present a novel way to detect the handedness of chiral materials with linearly polarized light. We performed Second Harmonic Generation (SHG) microscopy on G-shaped planar chiral nanostructures made of gold. The SHG response originates in distinctive hotspots, whose arrangement is dependent of the handedness. These results uncover new directions for studying chirality in artificial materials. PMID- 20588675 TI - Lidar signature from bubbles in the sea. AB - The lidar signature from a collection of bubbles is proportional to the volume backscatter coefficient at a scattering angle of 180 degrees . This quantity, calculated using a combination of geometric optics and diffraction, is proportional to the void fraction of the bubbles in the water for any bubble size distribution. The constant of proportionality is 233 m(-1) sr(-1)for clean bubbles, slightly less for bubbles coated with a thin layer of organic material, and as large as 1445 m(-1) sr(-1) for a thick coating of protein. PMID- 20588676 TI - Thermal and optical properties of the femtosecond-laser-structured and stress induced birefringent regions in sapphire. AB - Temperature diffusivity of laser micro-structured regions in sapphire is determined by a temperature wave method with a lateral resolution reduced to ~10 microm using a directly sputtered micro-sensor and heater. A record high reduction of the temperature diffusivity of sapphire by 12% from its (1.26+/ 0.02) x 10(-5)m(2)/s in-bulk value inside the femtosecond laser-structured volumes is determined; in a BK7 glass (~4.8x10(-7) m(2)/s), a 2% decrease of the thermal diffusivity has been observed. Origin of the reduction is consistent with disorder and scattering of phonons around the laser photo-modified micro-volumes. The stress-induced birefringence is directly measured by polariscopy together with its radial distribution, and azimuthal orientation of the polarization ellipsis near the laser structured regions in sapphire. The maximum birefringence of Deltan approximately 1x10(-3) is achieved without crack formation and corresponds to a local stress of ~1.3 GPa. The stress (and birefringence) decay radially with a single-exponential constant of tau(R) = 24 microm while the azimuthal orientation of the polarization ellipsis is spiraling around the laser structured volume. Such structures are promising in waveguiding and lasing applications of optical vortices where spatial control of birefringence and optical activity are required. PMID- 20588677 TI - A static Fourier transform spectrometer for atmospheric sounding: concept and experimental implementation. AB - Spaceborne remote sensing can be used to retrieve the atmospheric composition and complement the surface or airborne measurement networks. In recent years, a lot of attention has been placed on the monitoring of carbon dioxide for an estimate of surface fluxes from the observed spatial and temporal gradients of its concentration. Although other techniques may be used to estimate atmospheric CO(2) concentration, the most promising for the near future is the absorption spectroscopy, focusing on the CO(2) absorption lines at 1.6 and/or 2.0 microns. For this objective, the French space agency (CNES) has developed a new spectrometer concept that is sufficiently compact to be placed onboard a microsatellite platform. The principle is that of a Fourier Transform Spectrometer (FTS), although the classical moving mirror is replaced by two sets of mirrors organized in steps. The interferogram is then imaged on a CCD matrix. The concept allows a very high resolving power, although limited to narrow spectral bands, which is well suited for the observation of a few CO(2) absorption lines. The laboratory model shows that a resolving power of about 65000 is achieved with a signal to noise on the spectra around 300. A modulating plate on the light path allows an easy of the path difference. Although this component adds some complexity to the instrument, it greatly improves the information content of the measurements. PMID- 20588678 TI - Impact of dispersion map design upon transmission performance of long-haul RZ DPSK system using dispersion flattened fiber. AB - This paper describes a theoretical study of the impact of dispersion map design upon the long-haul RZ-DPSK system using the dispersion flattened fiber. Numerical simulations are conducted to clarify the transmission performance of different dispersion map designs. As a result, number of dispersion blocks has a significant impact upon the transmission performance, and reduction of the number improves the nonlinear tolerance of the system. PMID- 20588680 TI - Graphene in a photonic metamaterial. AB - We demonstrate a photonic metamaterial that shows extraordinary sensitivity to the presence of a single atomic layer of graphene on its surface. Metamaterial's optical transmission increases multi-fold at the resonance frequency linked to the Fano-type plasmonic mode supported by the periodic metallic nanostructure. The experiments were performed with chemical vapor deposited (CVD) graphene covering a number of size-scaled metamaterial samples with plasmonic modes at different frequencies ranging from 167 to 187 Thz. PMID- 20588679 TI - General Bayesian estimation for speckle noise reduction in optical coherence tomography retinal imagery. AB - An important image post-processing step for optical coherence tomography (OCT) images is speckle noise reduction. Noise in OCT images is multiplicative in nature and is difficult to suppress due to the fact that in addition the noise component, OCT speckle also carries structural information about the imaged object. To address this issue, a novel speckle noise reduction algorithm was developed. The algorithm projects the imaging data into the logarithmic space and a general Bayesian least squares estimate of the noise-free data is found using a conditional posterior sampling approach. The proposed algorithm was tested on a number of rodent (rat) retina images acquired in-vivo with an ultrahigh resolution OCT system. The performance of the algorithm was compared to that of the state-of-the-art algorithms currently available for speckle denoising, such as the adaptive median, maximum a posteriori (MAP) estimation, linear least squares estimation, anisotropic diffusion and wavelet-domain filtering methods. Experimental results show that the proposed approach is capable of achieving state-of-the-art performance when compared to the other tested methods in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge preservation, and equivalent number of looks (ENL) measures. Visual comparisons also show that the proposed approach provides effective speckle noise suppression while preserving the sharpness and improving the visibility of morphological details, such as tiny capillaries and thin layers in the rat retina OCT images. PMID- 20588681 TI - Line coding to enhance the performance of 10-Gb/s CPFSK-ASK directly modulated signals. AB - The major drawback of frequency modulation (FM)-based directly modulated laser (DML) is its non-uniform FM response at low frequency range which gives rise to a severe pattern-dependent performance degradation. In this paper, we investigate the use of line coding to deplete the low-frequency spectral contents of the signal and thus to alleviate the degradation. We examine various line codes (8B/10B, 5B/6B, 7B/8B, 9B/10B, and 64B/66B) with continuous-phase frequency-shift keying/ amplitude-shift keying (CPFSK/ASK) signals generated using a DML and a delay interferometer. Experimental demonstrations are performed with a long pseudorandom bit sequence length of 2(20)-1 and the bandwidth expansion by each code is taken into consideration. The results show that among the five codes we tested, 9B/10B code outperforms the other codes in terms of receiver sensitivity an dispersion tolerance. We demonstrate successful transmission of 10-Gb/s CPFSK ASK signals over 65-km standard single-mode fiber with a bandwidth expansion of only 11.1%. PMID- 20588682 TI - Coupled mode theory analysis of mode-splitting in coupled cavity system. AB - We analyze transmission characteristics of two coupled identical cavities, of either standing-wave (SW) or traveling-wave (TW) type, based on temporal coupled mode theory.Mode splitting is observed for both directly (cavity-cavity) and indirectly (cavity-waveguide-cavity) coupled cavity systems. The effects of direct and indirect couplings, if coexisting in one system, can offset each other such that no mode splitting occurs and the original single-cavity resonant frequency is retained. By tuning the configuration of the coupled cavity system, one can obtain different characteristics in transmission spectra, including splitting in transmission, zero transmission, Fano-type transmission, electromagnetically-induced-transparency (EIT)-like transmission, and electromagnetically-induced-absorption (EIA)-like transmission. It is also interesting to notice that a side-coupled SW cavity system performs similarly to an under-coupled TW cavity. The results are useful for the design of cavity-based devices for integration in nanophotonics. PMID- 20588683 TI - Design of binary diffractive microlenses with subwavelength structures using the genetic algorithm. AB - We present a method to design binary diffractive microlenses with subwavelength structures, based on the finite-difference time-domain method and the genetic algorithm, also accounting for limitations on feature size and aspect ratio imposed by fabrication. The focusing efficiency of the microlens designed by this method is close to that of the convex lens and much higher than that of the binary Fresnel lens designed by a previous method. Although the optimized structure appears to be a binary Fresnel lens qualitatively, it is hard to quantitatively derive directly from the convex Fresnel lens. The design of a microlens with reduced chromatic aberration is also presented. PMID- 20588684 TI - Flexible polymer waveguide tunable lasers. AB - A flexible polymeric Bragg reflector is fabricated for the purpose of demonstrating widely tunable lasers with a compact simple structure. The external feedback of the Bragg reflected light into a superluminescent laser diode produces the lasing of a certain resonance wavelength. The highly elastic polymer device enables the direct tuning of the Bragg wavelength by controlling the imposed strain and provides a much wider tuning range than silica fiber Bragg gratings or thermo-optic tuned polymer devices. Both compressive and tensile strains are applied within the range from -36000 microepsilon to 35000 microepsilon, so as to accomplish the continuous tuning of the Bragg reflection wavelength over a range of up to 100 nm. The external feedback laser with the tunable Bragg reflector exhibits a repetitive wavelength tuning range of 80 nm with a side mode suppression ratio of 35 dB. PMID- 20588685 TI - Generation of J(0) Bessel beams with controlled spatial coherence features. AB - An alternative method to generate J(0) Bessel beams with controlled spatial partial coherence properties is introduced. Far field diffraction from a discrete number of source points on an annular region is calculated. The average for different diffracted fields produced at several rotation angles is numerically calculated and experimentally detected. Theoretical and experimental results show that for this particular case, the J(0) Bessel beam is a limit when the number of points tends towards infinity and the associated complex degree of coherence is also a function of the number of points. PMID- 20588686 TI - Submilliwatt thermo-optic switches using free-standing silicon-on-insulator strip waveguides. AB - A low power Mach-Zehnder interferometer thermo-optic switch using free-standing silicon-on-insulator strip waveguides is demonstrated. The air gap provides thermal isolation between the waveguide interferometer arms and the underlying silicon substrate. The highly confined optical modes of the strip waveguides enable miniature heated cross-sections. The heating efficiency from on-chip resistive heaters is enhanced. Measurements of fabricated devices using 100 microm arm lengths at 1550 nm wavelength result in a switching power of 540 microW, a 10% - 90% switching rise time of 141 micros, and an extinction ratio of 25 dB. PMID- 20588687 TI - Monolithic integration and synchronous operation of germanium photodetectors and silicon variable optical attenuators. AB - We demonstrate the monolithic integration of germanium (Ge) p-i-n photodetector (PDs) with silicon (Si) variable optical attenuator (VOAs) based on submicrometer Si rib waveguide. A PD is connected to a VOA along the waveguide via a tap coupler. The PDs exhibit low dark current of ~60 nA and large responsivity of ~0.8 A/W at the reverse bias of 1 V at room temperature. These characteristics are uniform over the chip scale. The PDs generate photocurrents precisely with respect to DC optical power attenuated by the VOAs. Two devices work synchronously for modulated optical signals as well. 3-dB cut-off frequency of the VOA is ~100 MHz, while that of the PD is ~1 GHz. The synchronous response speed is limited by the VOA response speed. This is the first demonstration, to the best of our knowledge, of monolithic integration of Ge PDs with high-carrier injection-based optical modulation devices based on Si. PMID- 20588688 TI - Mesoscopic epifluorescence tomography: reconstruction of superficial and deep fluorescence in highly-scattering media. AB - Mesoscopic Epifluorescence Tomography (MEFT) is a technique derived from Laminar Optical Tomography (LOT), determining fluorescence biodistribution by tomographic means in reflectance geometry. A pencil beam is scanned over the region of interest to excite fluorophores hidden within the tissue, while a CCD camera acquires images of reflected fluorescence emissions. This configuration is advantageous whenever transillumination of the specimen is not feasible, e.g., in the presence of skin chambers or when using wavelengths in the visible range where absorption is high. We present simulation and phantom studies recovering deep GFP-like fluorescence in highly scattering and strongly absorbing media with a penetration depth up to 10mm. PMID- 20588689 TI - Photonic lanterns: a study of light propagation in multimode to single-mode converters. AB - The "photonic lantern," an optical fibre device that has emerged from the field of astrophotonics, allows for a single-mode photonic function to take place within a multimode fibre. We study and evaluate the modal behaviour of photonic lanterns as well as the conditions for achieving low-loss between a multimode fibre and a "near-diffraction limited" single-mode system. We also present an intuitive analogy of the modal electromagnetic propagation behaviour along the photonic lantern transition in terms of the Kronig-Penney model in Quantum Mechanics. PMID- 20588690 TI - Wave analysis of Airy beams. AB - The Airy beams are analyzed in order to provide a cogent physical explanation to their intriguing features which include weak diffraction, curved propagation trajectories in free-space, and self healing. The asymptotically exact analysis utilizes the method of uniform geometrical optics (UGO), and it is also verified via a uniform asymptotic evaluation of the Kirchhoff-Huygens integral. Both formulations are shown to fully agree with the exact Airy beam solution in the paraxial zone where the latter is valid, but they are also valid outside this zone. Specifically it is shown that the beam along the curved propagation trajectory is not generated by contributions from the main lobe in the aperture, i.e., it is not described by a local wave-dynamics along this trajectory. Actually, this beam is identified as a caustic of rays that emerge sideways from points in the initial aperture that are located far away from the main lobe. The field of these focusing rays, described h e by the UGO, fully agrees with the Airy beam solution. These observations explain that the "weak-diffraction" and the "self healing" properties are generated, in fact, by a continuum of sideways contributions to the field, and not by local self-curving dynamics. The uniform ray representation provides a systematic framework to synthesize aperture sources for other beam solutions with similar properties in uniform or in non-uniform media. PMID- 20588691 TI - Image capture via a wedge light-guide with no margins. AB - We report the capture of images via a wedge light-guide without the margin for fan-in needed heretofore. While this lets one look out of a slim panel as if it were a periscope, half the power is lost and resolution is degraded by aperture diffraction. Volume gratings may resolve these drawbacks at certain wavelengths and we consider how these might be extruded. PMID- 20588692 TI - Optical pulse coding in hybrid distributed sensing based on Raman and Brillouin scattering employing Fabry-Perot lasers. AB - We demonstrate simultaneous strain and temperature sensing based on hybrid Raman and Brillouin scattering with enhanced performance thanks to the combined use of standard Fabry-Perot lasers in conjunction with optical pulse coding techniques. The combination of both techniques allows for an improvement of ~8.7 dB in temperature resolution and ~3 dB in strain resolution, with respect to standard distributed feedback lasers, as confirmed by experiments, resulting in a final temperature / strain resolution of ~0.27K / ~30microepsilon over 25-km sensing fiber range, avoiding the use of optical amplification and wavelength averaging techniques. PMID- 20588693 TI - Silicon nanocrystals on bottle resonators: mode structure, loss mechanisms and emission dynamics. AB - Bottle resonators can support high Q-factor whispering gallery modes (WGMs) and demonstrate a rich mode spectrum. Resonators were fabricated using a fiber tapering apparatus and were coated with a thin, smooth layer of luminescent silicon nanocrystals. The photoluminescence spectrum showed WGM peaks with Q factors near 2,500; however, evanescent measurements showed that these modes are a composite of many modes with Q-factors exceeding 106, the highest yet seen for a silicon-nanocrystalcoated microresonators. The mode structure showed strong polarization and sensitivity to position within the bottle resonator. An analysis of loss mechanisms establishes surface roughness scattering as the limiting factor in these nanocrystal-coated bottle resonators in the absence of excited carriers. PMID- 20588694 TI - Optical 45 degrees hybrid for demodulating 8-ary DPSK signal. AB - We propose a novel optical 45 degrees hybrid employing a 2 x 8 paired interference based multimode interference (MMI) coupler, three phase shifters and three 2 x 2 optical couplers. Since the proposed 45 degrees hybrid can demodulate an 8-ary differential phase shift keyed (8-DPSK) signal with only one delayed Mach-Zehnder interferometer (DMZI), the demodulator has simpler configuration and much smaller device dimensions than conventional 8-DPSK demodulators consisting of four pairs of DMZIs and 2 x 2 optical couplers. We calculate and experimentally demonstrate octagonal phase response of the proposed 45 degrees hybrid with a relative phase deviation of < +/- 5 degrees over 32-nm-wide spectral range. PMID- 20588695 TI - A simple scanless two-photon fluorescence microscope using selective plane illumination. AB - We demonstrate a simple scanless two-photon (2p) excited fluorescence microscope based on selective plane illumination microscopy (SPIM). Optical sectioning capability is presented and depth-resolved imaging of cameleon protein in C. elegans pharyngeal muscle is implemented. PMID- 20588696 TI - Discrete dipole approximation for the study of radiation dynamics in a magnetodielectric environment. AB - We develop a general computational approach, based on the discrete dipole approximation, for the study of radiation dynamics near or inside an object with arbitrary linear dielectric permittivity, and magnetic permeability tensors. Our method can account for dispersion and losses and provides insight on the role of local-field corrections in discrete magnetodielectric structures. We illustrate our method in the case of a source inside a magneto-dielectric, isotropic sphere for which the spontaneous emission rate of a source can be computed analytically. We show that our approach is in excellent agreement with the exact result, providing an approach capable of handling both the electric and magnetic response of advanced metamaterials. PMID- 20588697 TI - Surface plasmon waveguide Schottky detector. AB - A surface plasmon polariton detector is demonstrated at infra-red wavelengths. The device consists of a metal stripe on silicon forming a Schottky contact thereon and supporting surface a plasmon polariton mode that is strongly confined and localised to the metal-semiconductor interface. Detection of optical radiation below the bandgap of silicon (at infrared wavelengths) occurs through internal photoemission. Responsivities of 0.38 and 1.04 mA/W were measured via end-fire coupling to a tapered optical fibre, at room temperature and at a wavelength of 1280 nm, for gold and aluminium stripes on n-type silicon, respectively. The device can be integrated with other structures used in nano plasmonics, nano-photonics or silicon-based photonics, and it holds promise for short-reach optical interconnects and power monitoring applications. PMID- 20588698 TI - Simultaneous high-resolution retinal imaging and high-penetration choroidal imaging by one-micrometer adaptive optics optical coherence tomography. AB - Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional high-isotropic-resolution retinal images in vivo. We developed AO-OCT with a 1.03 mum probing beam and demonstrated high-penetration, high-resolution retinal imaging. Axial scans are acquired with a speed of 47,000 lines/s. AO closed loop is configured with a single deformable mirror. Seven eyes of 7 normal subjects were examined. Signal enhancement was found for all subjects. A rippled interface between nerve fiber layer and ganglion cell layer, boundary between ganglion cell layer and inner plexiform layer, and chorioscleral interface were identified. Simultaneous high-resolution and high-penetration choroidal imaging may be useful for microstructural investigation of photoreceptors and glaucomatous nerve-fiber abnormalities. PMID- 20588699 TI - Rigorous modal analysis of silicon strip nanoscale waveguides. AB - A full-vectorial H-field Finite Element Method has been used for the rigorous modal analysis of silicon strip waveguides. The spatial variation of the full vectorial H and E-fields are also discussed in details and further, the Poynting vector is also presented. The modal area, hybridness, single mode operation and birefringence are also described for such silicon strip waveguides. PMID- 20588700 TI - 50W CW visible laser source at 589nm obtained via frequency doubling of three coherently combined narrow-band Raman fibre amplifiers. AB - We demonstrate the cascaded coherent collinear combination of a seed-split triplet of 1178nm high-power narrow-band (sub-1.5MHz) SBS-suppressed CW Raman fibre amplifiers via nested free-space constructive quasi-Mach-Zehnder interferometry, after analysing the combination of the first two amplifiers in detail. Near-unity combination and cascaded-combination efficiencies are obtained at all power levels up to a maximum P(1178) > 60W. Frequency doubling of this cascaded-combined output in an external resonant cavity yields P(589) > 50W with peak conversion efficiency eta(589) ~85%. We observe no significant differences between the SHG of a single, combined pair or triplet of amplifiers. Although the system represents a successful power scalability demonstrator for fibre-based Na D(2a)-tuned mesospheric laser-guide-star systems, we emphasise its inherent wavelength versatility and consider its spectroscopic and near-diffraction limited qualities equally well suited to other applications. PMID- 20588701 TI - Adaptively modulated optical OFDM modems utilizing RSOAs as intensity modulators in IMDD SMF transmission systems. AB - Detailed investigations of the transmission performance of adaptively modulated optical orthogonal frequency division multiplexed (AMOOFDM) signals converted using reflective semiconductor optical amplifiers (RSOAs) are undertaken over intensity-modulation and direct-detection (IMDD) single-mode fiber (SMF) transmission systems for WDM-PONs. The theoretical RSOA model adopted for modulating the AMOOFDM signals is experimentally verified rigorously in the aforementioned transmission systems incorporating recently developed real-time end-to-end OOFDM transceivers. Extensive performance comparisons are also made between RSOA and SOA intensity modulators. Optimum RSOA operating conditions are identified, which are independent of RSOA rear-facet reflectivity and very similar to those corresponding to SOAs. Under the identified optimum operating conditions, the RSOA and SOA intensity modulators support the identical AMOOFDM transmission performance of 30Gb/s over 60km SMFs. Under low-cost optical component-enabled practical operating conditions, RSOA intensity modulators with rear-facet reflectivity values of >0.3 outperform considerably SOA intensity modulators in transmission performance, which decreases significantly with reducing RSOA rear-facet reflectivity and optical input power. In addition, results also show that use can be made of the RSOA/SOA intensity modulation induced negative frequency chirp to improve the AMOOFDM transmission performance in IMDD SMF systems. PMID- 20588702 TI - Study on scattering coefficient of surface plasmon polariton waves at interface of two metal-dielectric waveguides by using G-GFSIEM method. AB - Generalized Green's Function Surface Integral Equation Method (G-GFSIEM) is used to study propagation of surface plasmon polariton waves at interface of two semi infinite metal-dielectric waveguides. Reflection, transmission, and scattering coefficients for structures with different dielectric constants are calculated by using this method and by using energy conservation law. Conditions where scattering coefficient is maximized or minimized are studied. It is found that by using appropriate materials with specified dielectric constants, structures with required reflection, transmission, and scattering coefficients can be designed. PMID- 20588703 TI - Decoy-state quantum key distribution with polarized photons over 200 km. AB - We report an implementation of decoy-state quantum key distribution (QKD) over 200 km optical fiber cable through photon polarization encoding. This is achieved by constructing the whole QKD system operating at 320 MHz repetition rate, and developing high-speed transmitter and receiver modules. A novel and economic way of synchronization method is designed and incorporated into the system, which allows to work at a low frequency of 40kHz and removes the use of highly precise clock. A final key rate of 15 Hz is distributed within the experimental time of 3089 seconds, by using super-conducting single photon detectors. This is longest decoy-state QKD yet demonstrated up to date. It helps to make a significant step towards practical secure communication in long-distance scope. PMID- 20588704 TI - Eliminating hotspots in a multi-chip LED array direct backlight system with optimal patterned reflectors for uniform illuminanceand minimal system thickness. AB - We propose an optical design process that significantly reduces the time and costs in direct backlight unit (BLU) development. In it, the basic system specifications are derived from the optical characteristics of RGB light-emitting diodes (LEDs) comprising the BLU. The driving currents are estimated to determine the theoretical RGB flux ratio for a desired white point. The number of LEDs needed to produce the target luminance is then calculated from the combined optical efficiencies of the components. Last, an appropriate array configuration is sought based on the illuminance distribution function for meeting the target uniformity. To showcase the design process we built two 42-inch triangular cluster arrays of 40 x 16 LED elements. When a flat reflective sheet was used, the minimum thickness required of the system to satisfy the target uniformity was 30 mm. Introducing a patterned reflective sheet removed hotspots that resulted from reducing the system thickness without the aid of additional optical components. Using an optimized patterned reflective sheet, reduction in system thickness as much as 5 mm was possible. PMID- 20588706 TI - Phase-locking of the beat signal of two distributed-feedback diode lasers to oscillators working in the MHz to THz range. AB - We present difference-frequency stabilization of free-running distributed feedback (DFB) diode lasers, maintaining a stable phase-lock to a local oscillator (LO) signal. The technique has been applied to coherent hybrid THz imaging which employs a high-power electronic radiation source emitting at 0.62 THz and electro-optic detectors. The THz radiation of the narrow-band emitter is mixed with the difference frequency of the DFB diode laser pair. The resulting intermediate frequency is phase-locked to the LO signal from a radio-frequency generator using a fast laser-current control loop. The stabilization scheme can be adapted readily to a wide range of applications which require stabilized laser beat-notes. PMID- 20588705 TI - Ultra-fast photoacoustic flow cytometry with a 0.5 MHz pulse repetition rate nanosecond laser. AB - In vivo photoacoustic (PA) flow cytometry (PAFC) has great potential for detecting disease-associated biomarkers in blood and lymph flow, as well as real time control of the efficacy of photothermal (PT) and other therapies through the counting of circulating abnormal objects. We report on a high speed PAFC with a Yb-doped fiber laser having a 0.5-MHz pulse repetition rate at a wavelength of 1064 nm, pulse width of 10 ns, and energy up to 100 microJ. This is the first biomedical application of PA and PT techniques operating at the highest pulse repetition rate of nanosecond lasers that provide 100-fold enhancement in detection speed of carbon nanotube clusters, as well as real-time monitoring of the flow velocity of individual targets through the width of PA signals. The laser pulse rate limits for PT and PA techniques depending on the sizes of laser beam and targets and flow velocity are discussed. We propose time-overlapping mode and generation of periodic nano- and microbubbles as PA-signal and PT therapy amplifiers, including discrimination of small absorbing targets among large ones. Taking into account the relatively low level of background signals from most biotissues at 1064 nm, our data suggest that a nanosecond Yb-doped fiber laser operating at high pulse repetition rate could be a promising optical source for time-resolved PA and PT cytometry, imaging, microscopy, and therapy, including detection of nanoparticles and cells flowing at velocities up to 2.5 m/s. PMID- 20588707 TI - A fast reconstruction algorithm for fluorescence molecular tomography with sparsity regularization. AB - Through the reconstruction of the fluorescent probe distributions, fluorescence molecular tomography (FMT) can three-dimensionally resolve the molecular processes in small animals in vivo. In this paper, we propose an FMT reconstruction algorithm based on the iterated shrinkage method. By incorporating a surrogate function, the original optimization problem can be decoupled, which enables us to use the general sparsity regularization. Due to the sparsity characteristic of the fluorescent sources, the performance of this method can be greatly enhanced, which leads to a fast reconstruction algorithm. Numerical simulations and physical experiments were conducted. Compared to Newton method with Tikhonov regularization, the iterated shrinkage based algorithm can obtain more accurate results, even with very limited measurement data. PMID- 20588708 TI - Chalcogenide microporous fibers for linear and nonlinear applications in the mid infrared. AB - A new type of microstructured fiber for mid-infrared light is introduced. The chalcogenide glass-based microporous fiber allows extensive dispersion engineering that enables design of flattened waveguide dispersion windows and multiple zero-dispersion points - either blue-shifted or red-shifted from the bulk material zero-dispersion point - including the spectral region of CO(2) laser lines approximately 10.6 microm. Supercontinuum simulations for a specific chalcogenide microporous fiber are performed that demonstrate the potential of the proposed microstructured fiber design to generate a broad continuum in the middle-infrared region using pulsed CO(2) laser as a pump. In addition, an analytical description of the Raman response function of chalcogenide As(2)Se(3) is provided, and a Raman time constant of 5.4 fs at the 1.54 microm pump is computed. What distinguishes the microporous fiber from the microwire, nanowire and other small solid-core designs is the prospect of extensive chromatic dispersion engineering combined with the low loss guidance created by the porosity, thus offering long interaction lengths in nonlinear media. PMID- 20588709 TI - Unveiling nonlinear effects in dense coherent optical WDM systems with Volterra series. AB - In this paper, the effect of fiber nonlinear effects on coherent optical WDM systems is investigated through numerical simulations. The analysis of the most relevant fiber nonlinear effects is made recurring to the Volterra series transfer function method, which allows us to quantify its impact on the transmission of multi-level modulated signals employing digital coherent receiver. The performance transmission is evaluated using vector analysis of the received signal's constellation where firstly we validate against split-step simulations that VSTF is suitable for optimizing coherent optical WDM transmission; then we evaluate the different contributions of the fiber nonlinear distortions imposed on the coherent optical QPSK, 8PSK and 16QAM channels by co propagating lower data rate intensity modulated channels. PMID- 20588710 TI - High spatial resolution distributed sensing in optical fibers by Brillouin gain profile tracing. AB - A novel BOTDA technique for distributed sensing of the Brillouin frequency in optical fibers with cm-order spatial resolution is proposed. The technique is based upon a simple modulation scheme, requiring only a single long pump pulse for acoustic excitation, and no subsequent interrogating pulse. Instead, the desired spatial mapping of the Brillouin response is extracted by taking the derivative of the probe signal. As a result, the spatial resolution is limited by the fall-time of the pump modulation, and the phenomena of secondary "echo" signals, typically appearing in BOTDA sensing methods based upon pre-excitation, is mitigated. Experimental demonstration of the detection of a Brillouin frequency variation significantly smaller than the natural Brillouin linewidth, with a 2cm spatial resolution, is presented. PMID- 20588711 TI - Experimental realization of a mode-locked parabolic Raman fiber oscillator. AB - We report here the first demonstration of a mode-locked fiber laser delivering parabolic pulses (similaritons) at 1534 nm. The use of a Raman-based gain medium potentially allows its implementation at any wavelength. The 22nJ output similariton pulses have a true parabolic shape both in the time and spectral domains and a linear chirp. Linear recompression close to Fourier limit is demonstrated allowing us to obtain 6 ps compressed pulses with a compression factor of 75. PMID- 20588712 TI - Precise fluorophore lifetime mapping in live-cell, multi-photon excitation microscopy. AB - Fluorophore excited state lifetime is a useful indicator of micro-environment in cellular optical molecular imaging. For quantitative sensing, precise lifetime determination is important, yet is often difficult to accomplish when using the experimental conditions favored by live cells. Here we report the first application of temporal optimization and spatial denoising methods to two-photon time-correlated single photon counting (TCSPC) fluorescence lifetime imaging microscopy (FLIM) to improve lifetime precision in live-cell images. The results demonstrated a greater than five-fold improvement in lifetime precision. This approach minimizes the adverse effects of excitation light on live cells and should benefit FLIM applications to high content analysis and bioimage informatics. PMID- 20588713 TI - Azobenzene liquid crystalline materials for efficient optical switching with pulsed and/or continuous wave laser beams. AB - This study compares optical switching capabilities of liquid crystal (LC) materials based on different classes of azobenzene dyes. LCs based on molecules containing benzene rings with nearly symmetrical pi-pi conjugation respond more efficiently to a cw beam than to a nanosecond laser pulse and maintain the changes induced by the beam for tens of hours. Using azo dye molecules containing two benzene rings with push-pull pi-pi conjugation we demonstrate high photosensitivity to both a cw beam as well as nanosecond laser pulse with only 1 s relaxation of light-induced changes in material properties. Even faster, 1 ms restoration time is obtained for azo dye molecules containing hetaryl (benzothiazole) ring with enhanced push-pull pi-pi conjugation. These materials respond most efficiently to pulsed excitation while discriminating cw radiation. PMID- 20588714 TI - Programmable photonic crystal nanobeam cavities. AB - We present dynamically reconfigurable photonic crystal nanobeam cavities, operating at ~1550 nm, that can be continuously and reversibly tuned over a 9.5 nm wavelength range. The devices are formed by two coupled nanobeam cavities, and the tuning is achieved by varying the lateral gap between the nanobeams. An electrostatic force, obtained by applying bias voltages directly to the nanobeams, is used to control the spacing between the nanobeams, which in turn results in tuning of the cavity resonance. The observed tuning trends were confirmed through simulations that modeled the electrostatic actuation as well as the optical resonances in our reconfigurable geometries. PMID- 20588715 TI - Microscopic cascading of second-order molecular nonlinearity: New design principles for enhancing third-order nonlinearity. AB - Herein, we develop a phenomenological model for microscopic cascading and substantiate it with ab initio calculations. It is shown that the concept of local microscopic cascading of a second-order nonlinearity can lead to a third order nonlinearity, without introducing any new loss mechanisms that could limit the usefulness of our approach. This approach provides a new molecular design protocol, in which the current great successes achieved in producing molecules with extremely large second-order nonlinearity can be used in a supra molecular organization in a preferred orientation to generate very large third-order response magnitudes. The results of density functional calculations for a well known second-order molecule, (para)nitroaniline, show that a head-to-tail dimer configuration exhibits enhanced third-order nonlinearity, in agreement with the phenomenological model which suggests that such an arrangement will produce cascading due to local field effects. PMID- 20588716 TI - Effects of asymmetric surface corrugations on fully metal-coated scanning near field optical microscopy tips. AB - We propose a new configuration for a fully metal coated scanning near field (SNOM) probe based on asymmetric corrugations in the metal coating. The variation in the metal surface induces coupling mechanisms leading to the creation of a localized hot spot under linearly polarized excitation. Field localization is an effect of paramount importance for resolution but cannot be achieved with standard axisymmetric fully metal-coated probes, unless a more cumbersome radially polarized excitation is used. Our simulations show that this promising structure allows one to simplify the mode injection procedures circumventing the need for a radially polarized beam. PMID- 20588718 TI - Positioning and localization of two-wavelength interferograms for wavefront reconstruction with volume holographic media. AB - This work studies both theoretically and experimentally the formation of the contour interference patterns generated by a two-wavelength real-time holographic interferometer. The resulting contour interference fringes are due to the intersection of the measured surface with parallel, equally spaced planes of constant elevation. The theoretical analysis describes how the spatial frequency of the elevation planes, their angular position, and the localization of the fringes depend on parameters of the optical setup. A theoretical model for fringe localization is developed and confirmed by the experiments, showing a strong dependence of the interferogram position on the slope of the studied surface. Due to the thick Bi(12)TiO(20) crystal employed as the storage medium the Bragg selectivity of the holographic readout is also considered. PMID- 20588717 TI - Time-resolved analysis of cavitation induced by CW lasers in absorbing liquids. AB - We present novel results on thermocavitation using a CW medium-power near infrared laser (lambda=975 nm) focused into a saturated copper nitrate saline solution. Due to the large absorption coefficient at the laser wavelength, the solution can be heated to its superheat limit (T(sh) approximately 270-300 degrees C). Superheated water undergoes explosive phase transition around T(sh) producing approximately half-hemispheric bubbles (gamma approximately 0.5) in close contact with the substrate. We report the temporal dynamic of the cavitation bubble, which is much shorter than previously reported under similar conditions. It was found that the bubble radius and pressure wave amplitude emitted on bubble collapse decreases exponentially with the power laser. Thermocavitation can be a useful tool for the generation of ultrasonic waves and controlled ablation for use in high-resolution lithography. PMID- 20588719 TI - Cell parameter measurement of a twisted nematic liquid crystal device using interferometric polarimeter under normal incidence. AB - Five cell parameters of a twisted nematic liquid crystal device (TNLCD), namely, cell gap, pretilt angle, twisted angle, rubbing angle, and phase retardation are precisely measured by the developed amplitude-sensitive heterodyne polarimeter (ASHP) simultaneously integrated with Yeh and Gu's transfer matrix and Lien's transfer matrix. This proposed method can characterize the five cell parameters under the arrangement of a single wavelength at normal incidence. In contrast to the conventional methods on cell parameter detection either by adopting a multiple wavelength laser beam at normal incidence or by using a single wavelength laser beam under oblique incident to TNLCD, this method presents the advantage of not only having a simple setup but also the possibility to measure simultaneously five cell parameters on the characterization of TNLCD at high speed. PMID- 20588720 TI - Generation and control of the spiraling zero-order Bessel beam. AB - We report on the generation of a spiraling zero order Bessel beam by means of conventional axicon and the phase hologram. Obtained results are in a fairly good agreement with the theoretical predictions. PMID- 20588721 TI - A "virtual-interferometer" technique for surface metrology. AB - We demonstrate a novel technique for performing aberration-corrected surface metrology within existing wavefront-feedback systems. Our technique uses several phase measurements to calculate phase differences that directly reveal the surface gradients of an object under test, due to orthogonal displacements of that object between measurements. We then apply a least-squares algorithm for surface reconstruction using the gradient information. This approach also removes static system aberrations, providing an absolute measurement of the surface profile. To date, we have profiled a number of test optics with 20- to 40-nm RMS error, where the accuracy is determined by the amount of angular crosstalk over the system aperture. PMID- 20588722 TI - Nanobeam photonic crystal cavity quantum dot laser. AB - The lasing behavior of one dimensional GaAs nanobeam cavities with embedded InAs quantum dots is studied at room temperature. Lasing is observed throughout the quantum dot PL spectrum, and the wavelength dependence of the threshold is calculated. We study the cavity lasers under both 780 nm and 980 nm pump, finding thresholds as low as 0.3 microW and 19 microW for the two pump wavelengths, respectively. Finally, the nanobeam cavity laser wavelengths are tuned by up to 7 nm by employing a fiber taper in near proximity to the cavities. The fiber taper is used both to efficiently pump the cavity and collect the cavity emission. PMID- 20588723 TI - Subwavelength metal-optic semiconductor nanopatch lasers. AB - We report on near infrared semiconductor nanopatch lasers with subwavelength scale physical dimensions (0.019 cubic wavelengths) and effective mode volumes (0.0017 cubic wavelengths). We observe lasing in the two most fundamental optical modes which resemble oscillating electrical and magnetic dipoles. The ultra-small laser volume is achieved with the presence of nanoscale metal patches which suppress electromagnetic radiation into free-space and convert a leaky cavity into a highly-confined subwavelength optical resonator. Such ultra-small lasers with metallodielectric cavities will enable broad applications in data storage, biological sensing, and on-chip optical communication. PMID- 20588724 TI - Out of plane mode conversion and manipulation of Surface Plasmon Polariton waves. AB - We propose a rigorous design method of structured gratings for out of plane mode conversion, line focusing and manipulation of Surface Plasmon Polariton (SPP) waves. Employing a blazed grating to incorporate the directionality of SPP launch, and at the same time controlling grating depth and chirp to account for the radiation loss and diffraction angle, it was possible to achieve high efficiency and flexible SPP to freespace mode conversion. Devices with advanced functionalities, such as balanced SPP power splitter, and SPP wavelength demultiplexer are demonstrated with over 75% of power efficiencies at reasonable working distances of less than several wavelengths. PMID- 20588725 TI - Synthesis and display of dynamic holographic 3D scenes with real-world objects. AB - A 3D scene is synthesized combining multiple optically recorded digital holograms of different objects. The novel idea consists of compositing moving 3D objects in a dynamic 3D scene using a process that is analogous to stop-motion video. However in this case the movie has the exciting attribute that it can be displayed and observed in 3D. We show that 3D dynamic scenes can be projected as an alternative to complicated and heavy computations needed to generate realistic looking computer generated holograms. The key tool for creating the dynamic action is based on a new concept that consists of a spatial, adaptive transformation of digital holograms of real-world objects allowing full control in the manipulation of the object's position and size in a 3D volume with very high depth-of-focus. A pilot experiment to evaluate how viewers perceive depth in a conventional single-view display of the dynamic 3D scene has been performed. PMID- 20588726 TI - An all-silicon, single-mode Bragg cladding rib waveguide. AB - In this paper, we demonstrate a direct method of fabricating an all-silicon, single-mode Bragg cladding rib waveguide using proton beam irradiation and subsequent electrochemical etching. The Bragg waveguide consists of porous silicon layers with a low index core of 1.4 that is bounded by eight bilayers of alternating high and low refractive index of 1.4 and 2.4. Here, the ion irradiation acts to reduce the thickness of porous silicon formed, creating an optical barrier needed for lateral confinement. Single-mode guiding with losses as low as approximately 1 dB/cm were obtained for both TE and TM polarization over a broad range of wavelengths from 1525 nm to 1625 nm. Such an approach offers a method for monolithic integration of Bragg waveguides in silicon, without the need for multiple processes of depositing alternating materials. PMID- 20588727 TI - Multi-projection of lenticular displays to construct a 256-view super multi-view display. AB - A new super multi-view (SMV) display system that enables the number of views to be increased is proposed. All three-dimensional (3D) images generated by multiple multi-view flat-panel displays are superimposed on a common screen using a multi projection system. The viewing zones of the flat-panel 3D display are produced in the pupils of the projection lenses and then imaged to the observation space by a screen lens. Sixteen flat-panel 3D displays having 16 views were used to construct a SMV display having 256 views. The 3D resolution was 256 x 192. The screen size was 10.3 inches. The horizontal interval of the viewing zones was 1.3 mm. PMID- 20588728 TI - Cathodo- and photoluminescence in Yb(3+)-Er(3+) co-doped PbF(2) nanoparticles. AB - We have prepared and studied the PbF(2):(Yb(3+),Er(3+)) co-doped nanoparticles, with chemical formula (Yb-Er)(x)Pb(1-x)F(2+x), where x = 0.29, Yb(3+)/Er(3+) = 6, and estimated the energy efficiency for their cathodoluminescence, mostly of Yb(3+), and up-conversion photoluminescence of Er(3+) to reach more than 0.5% and 20%, respectively, which may be the highest to date for rare-earth doped nanoparticles. Electron beam induced temperature rise in the nanoparticles has been estimated by measuring the ratio of green emission bands of Er(3+). These high efficiencies are due to high doping level of nanoparticles and due to low phonon energy of the PbF(2) host. PMID- 20588729 TI - Compact all-fiber high-energy fiber laser with sub-300-fs duration. AB - We report a compact all-fiber high-energy fiber laser that consists of a laser oscillator and a compression section. The laser oscillator generates the pulses with high energy and large chirp. The compression section is made of a piece of standard single-mode fiber that dechirps the chirped pulses. The compact all fiber fiber laser produces pulses with 8 nJ of the pulse energy and 290 fs of the pulse duration. PMID- 20588730 TI - Microstructured KY(WO(4))(2):Gd(3+), Lu(3+), Yb(3+) channel waveguide laser. AB - Epitaxially grown, 2.4-microm-thin layers of KY(WO(4))(2):Gd(3+), Lu(3+), Yb(3+), which exhibit a high refractive index contrast with respect to the undoped KY(WO(4))(2) substrate, have been microstructured by Ar beam milling, providing 1.4-microm-deep ridge channel waveguides of 2 to 7 microm width, and overgrown by an undoped KY(WO(4))(2) layer. Channel waveguide laser operation was achieved with a launched pump power threshold of only 5 mW, a slope efficiency of 62% versus launched pump power, and 76 mW output power. PMID- 20588731 TI - Vortex solitons in lasers with feedback. AB - We report on the existence, stability and dynamical properties of two-dimensional self-localized vortices with azimuthal numbers up to 4 in a simple model for lasers with frequency-selective feedback.We build the full bifurcation diagram for vortex solutions and characterize the different dynamical regimes. The mathematical model used, which consists of a laser rate equation coupled to a linear equation for the feedback field, can describe the spatiotemporal dynamics of broad area vertical cavity surface emitting lasers with external frequency selective feedback in the limit of zero delay. PMID- 20588733 TI - Control of the collapse of bimodal light beams by magnetically tunable birefringences. AB - Using a system of coupled nonlinear Schrodinger equations (CNLSEs), we show that nonlinear light propagation in self-focusing Kerr media can be controlled via a suitable combination of linear and circular birefringences. In particular, magneto-optical effects are taken as a specific physical example, which enables the introduction of both types of birefringences simultaneously via the joint action of the Cotton-Mouton and the Faraday effect. We demonstrate the efficient management of the collapse of (2 + 1)D beams in magneto-optic dielectric media, which may result in either the acceleration or the suppression of the collapse. However, our study also shows that a complete stabilization of the bimodal beams (i.e., the propagation of two-dimensional solitary waves) is not possible under the proposed conditions. The analysis is performed by directly numerically solving the CNLSEs, as well as by using the variational approximation, both showing consistent results. The investigated method allows high-power beam propagation in Kerr media while avoiding collapse, thus offering a viable alternative to the techniques applied in non-instantaneous and/or non-local nonlinear media. PMID- 20588732 TI - Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. AB - Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image guided photothermal therapy. PMID- 20588734 TI - Study of optical anisotropies in benzocyclobutene thin films for the efficient design of optical waveguide devices. AB - We study the in-plane/out-of-plane anisotropies in refractive indices (n) and in thermo-optic coefficients (dn/dT) of benzocyclobutene (BCB) thin film on a substrate. Both nonoxidized and oxidized films are investigated. Aside from the stress-induced effects, oxidation has significant influence on the refractive index anisotropy. The dependence of the anisotropy on each of the thermal stress and the oxidation is determined quantitatively. The anisotropies in the dn/dT values are mainly caused by the thermal stress and are independent of oxidation. However, the original (stress-free) thermo-optic coefficients are obtained as isotropic and significantly different than the measured dn/dT values. Our findings have the potential to optimize the design of polarization insensitive and/or athermal BCB optical waveguide devices. PMID- 20588735 TI - Higher order guided mode propagation in solid-core photonic bandgap fibers. AB - We investigate higher order core-modes of solid-core photonic bandgap fibers experimentally and theoretically. We observe that for some wavelengths ranges the second mode is guided while the fundamental mode is not. We interpret this behavior in terms of the band diagrams and full numerical simulations, in good agreements with experiments. The sole guidance of the second, ring shaped modes observed at the edges of bandgaps could be of use for generation of vortex beams. PMID- 20588736 TI - Broadband external cavity tunable quantum dot lasers with low injection current density. AB - Broadband grating-coupled external cavity laser, based on InAs/GaAs quantum dots, is achieved. The device has a wavelength tuning range from 1141.6 nm to 1251.7 nm under a low continuous-wave injection current density (458 A/cm(2)). The tunable bandwidth covers consecutively the light emissions from both the ground state and the 1st excited state of quantum dots. The effects of cavity length and antireflection facet coating on device performance are studied. It is shown that antireflection facet coating expands the tuning bandwidth up to ~150 nm, accompanied by an evident increase in threshold current density, which is attributed to the reduced interaction between the light field and the quantum dots in the active region of the device. PMID- 20588737 TI - 3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea. AB - Capable of three-dimensional imaging of the cornea with micrometer-scale resolution, spectral domain-optical coherence tomography (SDOCT) offers potential advantages over Placido ring and Scheimpflug photography based systems for accurate extraction of quantitative keratometric parameters. In this work, an SDOCT scanning protocol and motion correction algorithm were implemented to minimize the effects of patient motion during data acquisition. Procedures are described for correction of image data artifacts resulting from 3D refraction of SDOCT light in the cornea and from non-idealities of the scanning system geometry performed as a pre-requisite for accurate parameter extraction. Zernike polynomial 3D reconstruction and a recursive half searching algorithm (RHSA) were implemented to extract clinical keratometric parameters including anterior and posterior radii of curvature, central cornea optical power, central corneal thickness, and thickness maps of the cornea. Accuracy and repeatability of the extracted parameters obtained using a commercial 859nm SDOCT retinal imaging system with a corneal adapter were assessed using a rigid gas permeable (RGP) contact lens as a phantom target. Extraction of these parameters was performed in vivo in 3 patients and compared to commercial Placido topography and Scheimpflug photography systems. The repeatability of SDOCT central corneal power measured in vivo was 0.18 Diopters, and the difference observed between the systems averaged 0.1 Diopters between SDOCT and Scheimpflug photography, and 0.6 Diopters between SDOCT and Placido topography. PMID- 20588738 TI - Spectrum narrowing of high power Tm: fiber laser using a volume Bragg grating. AB - Efficient operation of a cladding pumped high power Tm: fiber laser with a volume Bragg grating (VBG) as wavelength selective and spectrally narrowing element is reported. The laser yielded over 112 W of diffraction limited output at 1988 nm with a spectral linewidth of ~12 pm for 279 W of launched pump power, corresponding to a slope efficiency with respect to launched pump power of 43.4%. No discernable difference was observed in terms of output power and slope efficiency when using a broadband highly reflective mirror in place of the VBG. PMID- 20588739 TI - The oriented spatial filter masks for electronic speckle pattern interferometry phase patterns. AB - we propose the oriented spatial filter masks for filtering in electronic speckle pattern interferometry (ESPI) phase fringe patterns. We establish the oriented derivative operator that only highlights noise without edges of an image. The noise in the image can be removed while still preserving the edges simply by subtracting the oriented derivative image from original image, which can be implemented with one pass of the oriented spatial filter mask. Further, we make an improvement on the oriented spatial filter mask for enhancing the smoothness. The performance of the oriented spatial filter masks is demonstrated via application to a simulated speckle phase fringe pattern and an experimentally obtained phase fringe pattern and comparison with other directional filtering methods. PMID- 20588740 TI - Synergy of adaptive thresholds and multiple transmitters in free-space optical communication. AB - Laser propagation through extended turbulence causes severe beam spread and scintillation. Airborne laser communication systems require special considerations in size, complexity, power, and weight. Rather than using bulky, costly, adaptive optics systems, we reduce the variability of the received signal by integrating a two-transmitter system with an adaptive threshold receiver to average out the deleterious effects of turbulence. In contrast to adaptive optics approaches, systems employing multiple transmitters and adaptive thresholds exhibit performance improvements that are unaffected by turbulence strength. Simulations of this system with on-off-keying (OOK) showed that reducing the scintillation variations with multiple transmitters improves the performance of low-frequency adaptive threshold estimators by 1-3 dB. The combination of multiple transmitters and adaptive thresholding provided at least a 10 dB gain over implementing only transmitter pointing and receiver tilt correction for all three high-Rytov number scenarios. The scenario with a spherical-wave Rytov number R=0.20 enjoyed a 13 dB reduction in the required SNR for BER's between 10( 5) to 10(-3), consistent with the code gain metric. All five scenarios between 0.06 and 0.20 Rytov number improved to within 3 dB of the SNR of the lowest Rytov number scenario. PMID- 20588741 TI - Planar long-period grating filter based on long-range surface plasmon mode of buried metal stripe waveguide. AB - We propose a planar long-period grating filter based on coupling between the long range surface plasmon mode and a cladding mode of a fully buried metal stripe waveguide. Using a 2.5-mm-long corrugation grating produced along the surface of an epoxy-clad aluminum stripe waveguide, we achieve a rejection band with a contrast of approximately 18 dB at the wavelength approximately 1500 nm, which can be tuned by approximately 25 nm with a temperature change of approximately 30 degrees C. The experimental results agree closely with the simulation results. The filter could find applications in surface-plasmon-based integrated-optic circuits and biosensors. PMID- 20588742 TI - Passively Q-switched photonic crystal fiber laser and intracavity optical parametric oscillator. AB - We report on a passively Q-switched photonic crystal fiber (PCF) laser with Cr(4+):YAG as a saturable absorber. Under a pump power of 14.2 W, the maximum pulse energy is up to 630 microJ with a pulse width of 36 ns at a repetition rate of 5.6 kHz. With an intracavity optical parametric oscillator, the passively Q switched PCF laser is used to generate the signal wave at 1515 nm. The output pulse energy of the signal wave is found to be 140 microJ with a pulse width as short as 1.0 ns at a repetition rate of 3.3 kHz. The very short pulse width leads to the peak power up to 140 kW. PMID- 20588743 TI - Momentum space analysis of multiphoton double ionization of helium by intense attosecond xuv pulses. AB - We investigate the momentum and energy distributions of the two electrons in multiphoton double ionization of He by intense attosecond xuv pulses, based on a two-dimensional model. Two different patterns of the momentum distributions are identified, corresponding to the uncorrelated and correlated channels, respectively. Our analysis of the electron correlations focuses on two-photon and three-photon double ionization processes for different pulse durations and for different time delays after the pulses. For both two-photon and three-photon cases, a clear correlation valley in energy distributions is found when both electrons are ejected in opposite directions. This is mostly attributed to the electron correlations during the ionization of the first electron. We also find that when two electrons are ejected in the same direction, their Coulomb repulsion has an significant influence on the electron energy distributions during the postionization stage. Finally, in the case of three photon double ionization, we observe that the effects of the Coulomb repulsion become much more complicated, and a new catch-up collision phenomena is observed in the energy distributions. PMID- 20588744 TI - Alignment structures of rotational wavepacket created by two strong femtosecond laser pulses. AB - We experimentally and theoretically study the alignment structures of the rotational wavepacket created by linear molecules and two strong femtosecond laser pulses. In the experiment, we observe that the alignment structures depend on the time delay between the two laser pulses. In the theory, we find that the alignment structures are composed of the self-coupling term and the cross coupling term. The contributions of these two terms are separately calculated. Their coherent superposition reproduces the alignment structures observed in the experiment. PMID- 20588745 TI - Optical nonlinearities in hydrogenated-amorphous silicon waveguides. AB - We experimentally measure the optical nonlinearities in hydrogenated-amorphous silicon (a-Si:H) waveguides through the transmission of ultra-short pulses. The measured two-photon absorption coefficient beta is 4.1 cm/GW and we obtain a 3.5pi nonlinear phase shift at 4.1 W coupled input power corresponding to a nonlinear refractive index n(2) of 4.210(-13) cm(2)/W. The measured nonlinear coefficient gamma = 2003 (Wm)(-1) is at least 5 times the value in crystalline silicon. The measured free carrier absorption coefficient sigma = 1.910(-16) cm(2) agrees with the values predicted from the Drude-Lorenz model. It is seen that a-Si:H exhibits enhanced nonlinear properties at 1550 nm and is a promising platform for nonlinear silicon photonics. PMID- 20588746 TI - Miniature all-silica optical fiber pressure sensor with an ultrathin uniform diaphragm. AB - This paper presents an all-silica miniature optical fiber pressure/acoustic sensor based on the Fabry-Perot (FP) interferometric principle. The endface of the etched optical fiber tip and silica thin diaphragm on it form the FP structure. The uniform and thin silica diaphragm was fabricated by etching away the silicon substrate from a commercial silicon wafer that has a thermal oxide layer. The thin film was directly thermally bonded to the endface of the optical fiber thus creating the Fabry-Perot cavity. Thin films with a thickness from 1microm to 3microm have been bonded successfully. The sensor shows good linearity and hysteresis during measurement. A sensor with 0.75 microm-thick diaphragm thinned by post silica etching was demonstrated to have a sensitivity of 11 nm/kPa. The new sensor has great potential to be used as a non-intrusive pressure sensor in a variety of sensing applications. PMID- 20588747 TI - Temperature control of Fano resonances and transmission in superconducting metamaterials. AB - Losses are the main evil that limits the use of metamaterials in practical applications. While radiation losses may be controlled by design, Joule losses are hereditary to the metamaterial structures. An exception is superconducting metamaterials, where Joule losses can be uniquely controlled with temperature in a very wide range. We put this in use by demonstrating temperature-dependent transmission in the millimeter-wave part of the spectrum in high-Tc superconducting cuprate metamaterials supporting sub-radiant resonances of Fano type. PMID- 20588748 TI - Nonlinear photoacoustics for measuring the nonlinear optical absorption coefficient. AB - We report a novel photoacoustic Z-scan (PAZ-scan) technique that combines the advantages offered by the conventional Z-scan method and the sensitivity of the photoacoustic detection. The sample is scanned through the focused laser beam and the generated photoacoustic signal is recorded using a 10 MHz focused ultrasound transducer. Since the signal strength is directly proportional to the optical absorption, PAZ-scan displays nonlinear behavior depicting the nonlinear optical absorption of the material. Among many advantages, our experiments on mouse blood show that PAZ-scan can potentially be used as a standard technique to calibrate contrast agents used in theranostics in general and photoacoustics in particular. PMID- 20588749 TI - More studies on metamaterials mimicking de Sitter space. AB - We estimate the dominating frequencies contributing to the Casimir energy in a cavity of meta- materials mimicking de Sitter space, by solving the eigenvalue problem of Maxwell equations. It turns out the dominating frequencies are the inverse of the size of the cavity, and the degeneracy of these frequencies also explains our previous result on the unusually large Casimir energy. Our result suggests that carrying out the experiment in laboratory is possible theoretically. PMID- 20588750 TI - Generalized refractive tunable-focus lens and its imaging characteristics. AB - Conventional lenses made from optical glass or plastics have fixed properties (e.g. focal length) that depend on the index of refraction and geometrical parameters of the lens. We present an approach to the problem of calculation of basic paraxial parameters and the third order aberration coefficients of compound optical elements analogical to classical lenses which are based on refractive tunable-focus lenses. A detailed theoretical analysis is performed for a simple tunable-focus lens, a generalized tunable-focus lens, a generalized tunable-focus lens with minimum spherical aberration, and three-element tunable-focus lens (a tunable-focus doublet). PMID- 20588751 TI - Optimization of enhanced absorption in 3D-woodpile metallic photonic crystals. AB - We present a detailed theoretical analysis which reveals a useful insight to understand the resonant dissipative behavior of 3D woodpile metallic photonic crystals in the spectral response. We observe that a small amount of structural parameter modifications can induce great flexibility to alter the properties of the absorption resonance with even an extremely narrow band width of ~13 nm. Analyzing the dispersive properties of the 3D woodpile metallic photonic crystals and performing thorough numerical simulations for the finite number of layers we found that the magnitude, band width, and tunability of enhanced absorption can be easily optimized, which can be of significance to design an efficient photonic crystal thermal emitter. PMID- 20588752 TI - Design of compact and smooth free-form optical system with uniform illuminance for LED source. AB - A feedback modification method based on variable separation mapping is proposed in the design of free-form optical system with uniform illuminance for LED source. In this method, the non-negligible size of LED source is taken into account, and a smooth optical system is established with single freeform surface regenerated by adding feedback to the lens design for a point light source. More rounds of feedback can improve the lens performance. As an example, a smooth free form lens with rectangular illuminance distribution is designed, and the illuminance uniformity is improved from 18.75% to 81.08% after eight times feedback. PMID- 20588753 TI - Internuclear-distance dependence of electron correlation in nonsequential double ionization of H(2). AB - Using three-dimensional classical ensembles, we have investigated the internuclear distance dependence of nonsequential double ionization (NSDI) of H(2) molecules by an 800 nm, 1x10(14) W/cm(2) laser pulse. For the internuclear distance R ranging from 2 to 12 a.u., the NSDI of H(2) provides rich correlation patterns in the two-electron momentum distributions. These correlation patterns essentially reveal different microscopic dynamics in NSDI process. Moreover, our calculations show that R approximately 4 a.u. is the critical distance for double ionization yield of H(2). These results are qualitatively explained based on the classical barrier expression model and back analysis. PMID- 20588754 TI - Low-crosstalk 2 x 2 thermo-optic switch with silicon wire waveguides. AB - We demonstrate a low-crosstalk 2 x 2 thermo-optic switch with silicon wire waveguides. The device is based on a 2 x 2 array of Mach-Zehnder interferometer (MZI) switches. Lowest crosstalk levels of -50 dB and -30 dB are obtained for 'bar' and 'cross' switching states, respectively. An intersection in the switch is important for low-crosstalk operation. The power consumption of one MZI element switch is 40 mW and the total power consumption of the device is at most 160 mW. PMID- 20588755 TI - Multispectral photoacoustic coded excitation imaging using unipolar orthogonal Golay codes. AB - We present a method to speed up the acquisition of multispectral photoacoustic data sets by using unipolar orthogonal Golay codes as excitation sequences for the irradiation system. Multispectral photoacoustic coded excitation (MS-PACE) allows acquiring photoacoustic data sets for two irradiation wavelengths simultaneously and separating them afterwards, thus improving the SNR or speeding up the measurement. We derive an analytical estimation of the SNR improvement using MS-PACE compared to time equivalent averaging. We demonstrate the feasibility of the method by successfully imaging a phantom composed of two dyes using unipolar orthogonal Golay codes as excitation sequence for two high power laser diodes operating at two different wavelengths. The experimental results show very good agreement with the theoretical predictions. PMID- 20588756 TI - A suspended core nanofiber with unprecedented large diameter ratio of holey region to core. AB - For a suspended core nanofiber, the holey region is expected to be as large as possible to propagate the light at wavelengths as long as possible. Additionally, a large holey region is significant for its applications in sensors. However, the fabrication of nanofiber with large holey region is still a challenge so far. In this paper a method, which involves pumping positive pressure of nitrogen gas in both the cane fabrication and fiber-drawing processes, was proposed. A suspended core nanofiber, with a core diameter of around 480 nm and an unprecedented diameter ratio of holey region to core (DRHC) of at least 62, was fabricated in the length of several hundred meters. Owing to the large holey region, the confinement loss of the suspended core nanofiber is insignificant when the wavelength of light propagated in it is 1700 nm. For this fabrication technique, the nanowire length, fabrication efficiency, and the uniformity in the diameter are much superior to those of the nanowires fabricated in other ways. Finally, single mode third harmonic generation was observed by this nanofiber under the pump of a 1557 nm femtosecond fiber laser. This work shows the prospect of fabrication of nanostructured waveguide in glass materials by an inflation technique. PMID- 20588757 TI - 1319 nm and 1338 nm dual-wavelength operation of LD end-pumped Nd:YAG ceramic laser. AB - In this paper, we demonstrate the efficient 1.3 um dual-wavelength operation of LD end-pumped Nd:YAG ceramic laser. With a plano-concave cavity, a maximum continuous-wave dual-wavelength output power of 5.92 W is obtained under an incident pump power of 20.5 W, giving a slope efficiency of 30.3% and an optical optical conversion efficiency of 29.0%. With Co(2+):LaMgAl(11)O(19) crystal as the saturable absorber, the passively Q-switched dual-wavelength operation is achieved for the first time to our knowledge. The maximum passively Q-switched average output power is 226 mW, the minimum pulse width is 15 ns, and the highest pulse repetition rate is 133 kHz. PMID- 20588758 TI - Casting method for producing low-loss chalcogenide microstructured optical fibers. AB - We report significant advances in the fabrication of low loss chalcogenide microstructured optical fiber (MOF). This new method, consisting in molding the glass in a silica cast made of capillaries and capillary guides, allows the development of various designs of fibers, such as suspended core, large core or small core MOFs. After removing the cast in a hydrofluoric acid bath, the preform is drawn and the design is controlled using a system applying differential pressure in the holes. Fiber losses, which are the lowest recorded so far for selenium based MOFs, are equal to the material losses, meaning that the process has no effect on the glass quality. PMID- 20588759 TI - Infrared laser induced lateral photovoltaic effect observed in Cu(2)O nanoscale film. AB - The large infrared lateral photovoltaic effect (LPE) based on semiconductor structures has been a challenge for a long time because the light in this region is hard to be absorbed. In this study, we report an unusual infrared laser induced LPE observed in sputtered Cu(2)O thin films. The maximum open-circuit lateral photovoltage can reach up to a remarkable value of 30.6mV under irradiation of Ti: Sapphire laser emitting 100 fs pulses at 2000 nm with pulse energy of 50 microJ. Temperature gradient induced by infrared laser is introduced to interpret this infrared induced LPV effect. The high position sensitivity reaching 15.3mV/mm and easier fabrication techniques suggests this oxidized film a potential candidate for the novel infrared photodetectors. PMID- 20588760 TI - All-reflective coupling of two optical cavities with 3-port diffraction gratings. AB - The shot-noise limited sensitivity of Michelson-type laser interferometers with Fabry-Perot arm cavities can be increased by the so-called power-recycling technique. In such a scheme the power-recycling cavity is optically coupled with the interferometer's arm cavities. A problem arises because the central coupling mirror transmits a rather high laser power and may show thermal lensing, thermo refractive noise and photo-thermo-refractive noise. Cryogenic cooling of this mirror is also challenging, and thus thermal noise becomes a general problem. Here, we theoretically investigate an all-reflective coupling scheme of two optical cavities based on a 3-port diffraction grating.We show that power recycling of a high-finesse arm cavity is possible without transmitting any laser power through a substrate material. The power splitting ratio of the three output ports of the grating is, surprisingly, noncritical. PMID- 20588761 TI - Characterization on five effective parameters of anisotropic optical material using Stokes parameters-Demonstration by a fiber-type polarimeter. AB - An analytical technique based on the Mueller matrix method and the Stokes parameters is proposed for extracting five effective parameters on the principal axis angle, phase retardance, diattenuation axis angle, diattenuation and optical rotation angle of anisotropic optical materials. The linear birefringence (LB) / circular birefringence (CB) properties and linear diattenuation (LD) properties are decoupled within the analytical model. The analytical method is then integrated with a genetic algorithm to extract the optical properties of samples with linear birefringence property using a fiber-based polarimeter. The result demonstrates the feasibility of analytical model in characterizing five effective parameters of anisotropic optical material. Also, it confirms that the proposed fiber-based polarimeter provides a simple alternative to existing fiber-based probes for parameter measurement in the near field or the remote environment. A low birefringence fiber-based polarimeter based on effective parameters and genetic algorithm without using a fiber polarization controller is first proposed confirmatively. PMID- 20588762 TI - A high-resolution, adaptive beam-shaping system for high-power lasers. AB - A high-resolution, high-precision beam-shaping system for high-power-laser systems is demonstrated. A liquid-crystal-on-silicon spatial light modulator is run in closed-loop to shape laser-beam amplitude and wavefront. An unprecedented degree of convergence is demonstrated, and important practical issues are discussed. Wavefront shaping for the applications in OMEGA EP laser is demonstrated, and other interesting examples are presented. PMID- 20588763 TI - Simultaneous two-dimensional phononic and photonic band gaps in opto-mechanical crystal slabs. AB - We demonstrate planar structures that can provide simultaneous two-dimensional phononic and photonic band gaps in opto-mechanical (or phoxonic) crystal slabs. Different phoxonic crystal (PxC) structures, composed of square, hexagonal (honeycomb), or triangular arrays of void cylindrical holes embedded in silicon (Si) slabs with a finite thickness, are investigated. Photonic band gap (PtBG) maps and the complete phononic band gap (PnBG) maps of PxC slabs with different radii of the holes and thicknesses of the slabs are calculated using a three dimensional plane wave expansion code. Simultaneous phononic and photonic band gaps with band gap to midgap ratios of more than 10% are shown to be readily obtainable with practical geometries in both square and hexagonal lattices, but not for the triangular lattice. PMID- 20588764 TI - Collinear generation of ultrashort UV and XUV pulses. AB - We demonstrate the collinear generation of few-femtosecond ultraviolet and attosecond extreme ultraviolet pulses via a combination of third-harmonic and high harmonic generation in noble gases. The ultrashort coherent light bursts are produced by focusing a sub-1.5-cycle near-infrared/visible laser pulse in two subsequent quasi-static noble gas targets. This approach provides an inherently synchronized pair of UV and XUV pulses, where the UV radiation has a photon energy of approximately 5 eV and a pulse energy of up to 1 microJ and the XUV radiation contains up to 3.5 10(6) XUV photons per shot with a photon energy exceeding 100 eV. This source represents a novel tool for future UV pump/XUV probe experiments with unprecedented time-resolution. PMID- 20588765 TI - Scatterer size-based analysis of optical coherence tomography images using spectral estimation techniques. AB - A novel spectral analysis technique of OCT images is demonstrated in this paper for classification and scatterer size estimation. It is based on SOCT autoregressive spectral estimation techniques and statistical analysis. Two different statistical analysis methods were applied to OCT images acquired from tissue phantoms, the first method required prior information on the sample for variance analysis of the spectral content. The second method used k-means clustering without prior information for the sample. The results are very encouraging and indicate that the spectral content of OCT signals can be used to estimate scatterer size and to classify dissimilar areas in phantoms and tissues with sensitivity and specificity of more than 90%. PMID- 20588766 TI - Resolving range ambiguity in a photon counting depth imager operating at kilometer distances. AB - Time-correlated single-photon counting techniques have recently been used in ranging and depth imaging systems that are based on time-of-flight measurements. These systems transmit low average power pulsed laser signals and measure the scattered return photons. The use of periodic laser pulses means that absolute ranges can only be measured unambiguously at low repetition rates (typically <100 kHz for > 1 km) to ensure that only one pulse is in transit at any instant. We demonstrate the application of a pseudo-random pattern matching technique to a scanning rangefinder system using GHz base clock rates, permitting the acquisition of unambiguous, three-dimensional images at average pulse rates equivalent to >10 MHz. Depth images with centimeter distance uncertainty at ranges between 50 m and 4.4 km are presented. PMID- 20588767 TI - A Michelson controlled-not gate with a single-lens astigmatic mode converter. AB - We propose and demonstrate experimentally a single lens design for an astigmatic mode converter that transforms the transverse mode of paraxial optical beams. As an application, we implement a controlled-not gate based on a Michelson interferometer in which the photon polarization is the control bit and the first order transverse mode is the target. As a further application, we also build a transverse mode parity sorter which can be useful for quantum information processing as a measurement device for the transverse mode qubit. PMID- 20588768 TI - Gain analysis of optically-pumped Si nanocrystal waveguide amplifiers on silicon substrate. AB - The SiO(2)/SiO(x)/SiO(2) strip-loaded waveguide on Si substrate with buried Si nanocrystals (Si-ncs) in SiO(x) layer is demonstrated to show the Si-nc dependent optical gain. The amplified spontaneous emission (ASE) spectrum at 750-850 nm is observed with central wavelength of 805 nm and 3dB spectral linewidth of 140 nm. The optical net modal gain and loss coefficients of 85.7 cm(-1) and 21 cm(-1), respectively, are determined from the waveguide length dependent ASE intensity. By attenuating 785-nm laser diode signal to inject the pumped SiO(2)/SiO(x)/SiO(2) strip-loaded waveguide, a small-signal power gain of 13.5 decibel (dB) is obtained. Increasing the laser diode power shows a significantly reduced power gain with a saturated output power due to the finite density of the optically pumped Si-ncs. The fitting of power-dependent gain with a gain saturated amplifier model reveals a peak gain of 35 dB and a saturation power of 1.1 nW for the SiO(2)/SiO(x):Si-nc/SiO(2)/Si strip-loaded waveguide. Similar output saturation is also observed with increasing pumping power. With the presence of optical gain in the optically pumped Si-ncs, the intended application will be the monolithic integration of the Si-nc based optical waveguide amplifier with the other on-board photonic integrated circuits for the future optical interconnect communication. PMID- 20588769 TI - Fidelity optimization for aberration-tolerant hybrid imaging systems. AB - Several phase-modulation functions have been reported to decrease the aberration variance of the modulation-transfer-function (MTF) in aberration-tolerant hybrid imaging systems. The choice of this phase-modulation function is crucial for optimization of the overall system performance. To prevent a significant loss in signal-to-noise ratio, it is common to enforce restorability constraints on the MTF, requiring trade of aberration-tolerance and noise-gain. Instead of optimizing specific MTF characteristics, we directly minimize the expected imaging-error of the joint design. This method is used to compare commonly used phase-modulation functions: the antisymmetric generalized cubic polynomial and fourth-degree rotational symmetric phase-modulation. The analysis shows how optimal imaging performance is obtained using moderate phase-modulation, and more importantly, the relative merits of the above functions. PMID- 20588770 TI - Improved beam quality from a high energy optical parametric oscillator using crystals with orthogonal critical planes. AB - We demonstrate with simulations and experiments that an optical parametric oscillator using two different crystals with orthogonal walk-off planes can generate a symmetric, high-quality beam even if the resonator has a high Fresnel number. In the experiments we used KTA and BBO crystals to convert 5 ns pulses at 1.06 microm to 1.7 microm pulses with more than 10 mJ energy and beam quality M(2) approximately 2. PMID- 20588771 TI - Staggered-grid PSTD on local Fourier basis and its applications to surface tissue modeling. AB - We introduce a high performance parallelization to the PSTD solution of Maxwell equations by employing the fast Fourier transform on local Fourier basis. Meanwhile a reformatted derivative operator allows the adoption of a staggered grid such as the Yee lattice in PSTD, which can overcome the numerical errors in a collocated-grid when spatial discontinuities are present. The accuracy and capability of our method are confirmed by two analytical models. In two applications to surface tissue optics, an ultra wide coherent backscattering cone from the surface layer is found, and the penetration depth of polarization gating identified. Our development prepares a tool for investigating the optical properties of surface tissue structures. PMID- 20588772 TI - Impulsive terahertz radiation with high electric fields from an amplifier-driven large-area photoconductive antenna. AB - We report on the generation of impulsive terahertz (THz) radiation with 36 kV/cm vacuum electric field (1.5 mW average thermal power) at 250 kHz repetition rate and a high NIR-to-THz conversion efficiency of 2 x 10(-3). This is achieved by photoexciting biased large-area photoconductive emitter with NIR fs pulses of microJ pulse energy. We demonstrate focussing of the THz beam by tailoring the pulse front of the exciting laser beam without any focussing element for the THz beam. A high dynamic range of 10(4) signal-to-noise is obtained with an amplifier based system. PMID- 20588773 TI - Phase-locking of two self-seeded tapered amplifier lasers. AB - We report on the phase-locking of two diode lasers based on self-seeded tapered amplifiers. In these lasers, a reduction of linewidth is achieved using narrow band high-transmission interference filters for frequency selection. The lasers combine a compact design with a Lorentzian linewidth below 200 kHz at an output power of 300 mW for a wavelength of 780 nm. We characterize the phase noise of the phase-locked laser system and study its potential for coherent beam-splitting in atom interferometers. PMID- 20588774 TI - Light diffusion in a turbid cylinder. II. Layered case. AB - This paper is the second of two dealing with light diffusion in a turbid cylinder. The diffusion equation was solved for an N-layered finite cylinder. Solutions are given in the steady-state, frequency, and time domains for a point beam incident at an arbitrary position of the first layer and for a circular flat beam incident at the middle of the cylinder top. For special cases the solutions were compared to other solutions of the diffusion equation showing excellent agreement. In addition, the derived solutions were validated by comparison with Monte Carlo simulations. In the time domain we also derived a fast solution ( approximately 10ms) for the case of equal reduced scattering coefficients and refractive indices in all layers. PMID- 20588775 TI - Optofluidic dye laser in a foil. AB - First order distributed feedback optofluidic dye lasers embedded in a 350 microm thick TOPAS((R)) foil are demonstrated. They are designed in order to give high output pulse energies. Microfluidic channels and first order distributed feedback gratings are fabricated in parallel by thermal nanoimprint into a 100 microm foil. The channels are closed by thermal bonding with a 250 microm thick foil and filled with 5.10(-3) mol/l Pyrromethene 597 in benzyl alcohol. The fluid forms a liquid core single mode slab waveguide of 1.6 microm height on a nanostructured grating area of 0.5 x 0.5 mm(2). This results in a large gain volume. Two grating periods of 185 nm and 190 nm yield single mode laser light emission at 566 nm and 581 nm respectively. High emitted pulse energies of more than 1 microJ are reported. Stable operation for more than 25 min at 10 Hz pulse repetition rate is achieved. PMID- 20588776 TI - Continuous control of the coupling constant in an atom-cavity system by using elliptic polarization and magnetic sublevels. AB - Atom-cavity coupling constant is a key parameter in cavity quantum electrodynamics for describing the interaction between an atom and a quantized electromagnetic field in a cavity. This paper reports a novel way to tune the coupling constant continuously by inducing an averaging of the atomic dipole moment over degenerate magnetic sublevels with elliptic polarization of the cavity field. We present an analytic solution of the stationary-state density matrix for this system with consideration of F -> F +1 hyperfine transition under a weak excitation condition. We rigorously show that the stationary-state emission spectra of this system can be approximated by that of a non-degenerate two-level atom with an effective coupling constant as a function of the elliptic angle of the cavity field only. A precise condition for this approximation is derived and its physical meaning is interpreted in terms of a population-averaged transition strength and its variance. Our results can be used to control the coupling constant in cavity quantum electrodynamics experiments with a degenerate two-level atom with magnetic sublevels. Possible applications of our results are discussed. PMID- 20588777 TI - Waveguide coupled photodiode using reflector and metal coplanar waveguide for optical triplexing applications. AB - The monitoring photodiode is the key building block for an optical triplexer at wavelengths of 1310, 1490, and 1550 nanometers. The InGaAs/InP photodetectors were proposed and fabricated to be monolithi-cally integrated with AlGaAs/GaAs optical waveguides using total internal reflection coupling. The metal coplanar waveguides on top of the polyimide planarization and passivation layer were then connected to illustrate the high speed monitoring functions. The full width half maximum of the temporal response and 3-dB bandwidth for the optical waveguide coupled photodiodes demonstrated 29.5 ps and 11 GHz, respectively. The bit error rate performance of this integrated photodiode at 10 Gbit/s with 2(7)-1 long pseudo-random bit sequence NRZ input data also showed error-free operation. PMID- 20588778 TI - Experimental demonstration of impedance match locking and control for coupled resonators. AB - We describe and verify the dynamic behavior of a novel technique to optimize and actively control the optical impedance matching condition of a coupled resonator system. The technique employs radio frequency modulation and demodulation to interrogate the reflection amplitude response of the coupled cavity system. The sign and magnitude of the demodulated signal is used in a closed loop feedback system which controls the coupling condition of a three-mirror resonator. This was done by actuating on the spacing between two of mirrors, effectively using the pair as a variable reflectivity compound mirror. We propose that this technique can be used for controlling the signal bandwidth of next-generation gravitational wave detectors, as well as optimizing circulating optical carrier power in the instrument. PMID- 20588779 TI - Simple all-optical FFT scheme enabling Tbit/s real-time signal processing. AB - A practical scheme to perform the fast Fourier transform in the optical domain is introduced. Optical real-time FFT signal processing is performed at speeds far beyond the limits of electronic digital processing, and with negligible energy consumption. To illustrate the power of the method we demonstrate an optical 400 Gbit/s OFDM receiver. It performs an optical real-time FFT on the consolidated OFDM data stream, thereby demultiplexing the signal into lower bit rate subcarrier tributaries, which can then be processed electronically. PMID- 20588780 TI - Blue-shifted contra-directional coupling between a periodic and conventional dielectric waveguides. AB - The interaction between a periodic and conventional dielectric waveguides is investigated theoretically for a two-dimensional model system. A modified coupled mode theory is formulated for the considered system and found to agree well with rigorous numerical calculations. It is shown that in a certain wavelength range the contra-directional coupling between the two waveguides can be achieved with high efficiency. But the spectrum of the coupling efficiency is blue-shifted and thus the strongest coupling does not occur in the case when two individual waveguides have the same propagation constant. For such a contra-directional coupling system, the coupling efficiency grows with the coupling length and it tends to 100% (excluding insertion loss) when the coupling length is larger than a certain value, and the coupling window can be largely broaden by reducing the distance between the coupled waveguides. PMID- 20588781 TI - Low-bias high-speed quantum random number generator via shaped optical pulses. AB - We present an optical quantum random number generator (QRNG) based on the digitized time interval between random photon arrivals. By tailoring the photon flux of the laser diode, the statistics of the waiting-time distribution are altered to approximate the ideal, uniform case. This greatly reduces the need for post-processing, and enables fast, secure quantum random number generation at rates exceeding 110 Mbit/s. PMID- 20588782 TI - Grating dynamics in a photorefractive polymer with Alq(3) electron traps. AB - The electron transporting molecule tris(8-hydroxyquinoline) aluminum (Alq(3)) was added in low concentrations to a photorefractive polymer composite to provide trapping sites for electrons. This sample exhibited larger two-beam coupling gain, higher diffraction efficiency at lower voltages, and an increased dielectric breakdown strength compared to a control sample. The dynamics also revealed the presence of a competing grating, and a bipolar charge transport model is shown to fit the data. Overall, Alq(3) improves the response time, efficiency, and breakdown voltage without a significant increase in absorption or loss of phase stability. This has applications for reflection displays and pulsed writing, where charge trapping and generation are major factors limiting the usefulness of photorefractive polymers. PMID- 20588783 TI - Analysis of time-multiplexed optical line-by-line pulse shaping: application for radio-frequency and microwave photonics. AB - Time-multiplexed optical line-by-line pulse shaping with specific application to rapid update radio-frequency (RF) waveform generation is modeled. The effects of fundamental pulse shaping parameters on generated RF waveforms are numerically analyzed. Experimental and theoretical results are compared and are in excellent agreement. PMID- 20588784 TI - Application of a passively mode-locked quantum-dot Fabry-Perot laser in 40 Gb/s all-optical 3R regeneration. AB - The application of a mode-locked quantum-dot Fabry-Perot (QD-FP) laser in a wavelength preserving all-optical 3R regenerator is demonstrated at 40 Gb/s. The 3R regenerator consists of a QD-FP laser for low-timing jitter clock recovery, cross-phase modulation based retiming, and self-phase modulation based reshaping. The performance of the alloptical 3R regenerator is assessed experimentally in terms of the Q-factor, timing jitter and bit-error ratio. PMID- 20588785 TI - Modeling of the SPR resolution enhancement for conventional and nanoparticle inclusive sensors by using statistical hypothesis testing. AB - This paper describes a statistical approach that improves the detection accuracy in simulated experimental surface plasmon resonance (SPR) systems operated in a conventional angular readout scheme. Two SPR system have been investigated: a conventional one and a second one, containing absorbing metallic nanoparticles within the sensing layer. The modified Maxwell-Garnett model that optimally describes the experimental literature results was applied to modeling of the nanoparticle-inclusive sensor. Statistical hypothesis testing was then used to determine the limit of detection of the analyte and nanoparticles. Analyte concentrations as low as 1 pM, corresponding to the refractive index change of 4x10(-8) have been detected with optimized metal layers operated close to the nanoparticle absorption maximum. This is about one order of magnitude smaller than the values obtained in conventional SPR systems with nanoparticles and comparable to the phase-sensitive surface plasmon resonance detection. PMID- 20588786 TI - Precise optical modeling of blue light-emitting diodes by Monte Carlo ray tracing. AB - Precise optical modeling of blue light-emitting diodes (LEDs) is constructed by reasonable optical parameters and Monte Carlo ray-tracing with the capability of precisely predicting light extraction and radiation pattern for both bare LED and packaged LED. Refractive indices and absorption coefficients of LED materials are determined by abundant references and comparisons between simulations and experiments. Surface roughness is considered in the optical model to improve the simulation precision. The simulation precisions are excellent for both bare blue LEDs (>96.5% for light extraction and >99% for radiation pattern) and packaged blue LEDs (>98.5% for both light extraction and radiation pattern). PMID- 20588787 TI - Performance of astronomical beam combiner prototypes fabricated by hybrid sol-gel technology. AB - Integrated optics coaxial two, three and four telescope beam combiners have been fabricated by hybrid sol-gel technology for astronomical applications. Temporal and spectral analyses of the output interferometric signal have been performed, and their results are in mutual good agreement. The results of the characterization method employed are cross-checked using contrast measurements obtained independently, demonstrating that the chromatic differential dispersion is the main contributer to contrast reduction. The mean visibility of the fabricated devices is always higher than 95 %, obtained using a source with spectral bandwidth of 50 nm. These results show the capability of hybrid sol-gel technology for fast prototyping of complex chip designs used in astronomical applications. PMID- 20588788 TI - Nonlinear dynamics induced by parallel and orthogonal optical injection in 1550 nm Vertical-Cavity Surface-Emitting Lasers (VCSELs). AB - We report a first experimental study of the nonlinear dynamics appearing in a 1550 nm single-mode VCSEL subject to parallel and to orthogonal optical injection. For the first time to our knowledge we report experimentally measured stability maps identifying the boundaries between regions of different nonlinear dynamics for both cases of polarized injection. A rich variety of nonlinear behaviours, including periodic (limit cycle, period doubling) and chaotic dynamics have been experimentally observed. PMID- 20588789 TI - Measurement of refractive index and thickness of transparent plate by dual wavelength interference. AB - We developed an accurate and efficient method for measuring the refractive indices of a transparent plate by analyzing the transmitted intensity versus angle of incidence. By using two different wavelengths, we resolved the 2pi ambiguity inherent to the phase measurement involving a thick medium, leading to independent determination of the absolute index of refraction and the thickness with a relative uncertainty of 10(-5). The validity and the accuracy of our method were confirmed with a standard reference material. Furthermore, our method is insensitive to environmental perturbations, and simple to implement, compared to the conventional index measurement methods providing similar accuracy. PMID- 20588790 TI - Multi-channel in-band OSNR monitoring using Stimulated Brillouin Scattering. AB - We investigate an optical performance monitor based on Stimulated Brillouin scattering (SBS), for enabling the measurement of the in-band optical signal to noise ratio (OSNR) for multiple channels of a wavelength-division multiplexed (WDM) signal simultaneously. The principle relies on propagating the signal in a nonlinear waveguide so that each channel pumps SBS to produce a back-scattered Stokes wave of unique carrier wavelength, and with a power that depends on the in band OSNR of the channel itself. We experimentally demonstrate a highly sensitive OSNR measurement for a 3 x 40 Gb/s signal, with a small sensitivity to the input state of polarization, and a large dynamic range (25 dB) in the Stokes power. Our results also reveal the insensitivity of SBS to both chromatic and polarization mode dispersions, and the indirect role these effects can play in mitigating the suppression of SBS from the nonlinear Kerr effect. PMID- 20588791 TI - Tuning of resonance-spacing in a traveling-wave resonator device. AB - In this work a traveling-wave resonator device is proposed and experimentally demonstrated in silicon-on-insulator platform in which the spacing between its adjacent resonance modes can be tuned. This is achieved through the tuning of mutual coupling of two strongly coupled resonators. By incorporating metallic microheaters, tuning of the resonance-spacing in a range of 20% of the free spectral-range (0.4nm) is experimentally demonstrated with 27mW power dissipation in the microheater. To the best of our knowledge this is the first demonstration of the tuning of resonance-spacing in an integrated traveling-wave-resonator. It is also numerically shown that these modes exhibit high field-enhancements which makes this device extremely useful for nonlinear optics and sensing applications. PMID- 20588792 TI - Light diffusion in a turbid cylinder. I. Homogeneous case. AB - This paper is the first of two dealing with light diffusion in a turbid cylinder. The diffusion equation was solved for a homogeneous finite cylinder that is illuminated at an arbitrary location. Three solutions were derived for an incident delta -light source in the steady-state, frequency, and time domains, respectively, applying different integral transformations. The performance of these solutions was compared with respect to accuracy and speed. Excellent agreement between the solutions, of which some are very fast (< 10ms), was found. Six of the nine solutions were extended to a circular flat beam which is incident onto the top side. Furthermore, the validity of the solutions was tested against Monte Carlo simulations. PMID- 20588793 TI - Fluorescence-based sensing with optical nanowires: a generalized model and experimental validation. AB - A model for the fluorescence sensing properties of small-core high-refractive index fibers (optical nanowires) is developed and compared quantitatively with experiment. For the first time, higher-order modes and loss factors relevant to optical nanowires are included, which allows the model to be compared effectively with experiment via the use of fluorophore filled suspended optical nanowires. Numerical results show that high-index materials are beneficial for fluorescence based sensing. However, both numerical and experimental results show that the fluorescence signal is relatively insensitive to core size, except for low concentration sensing where nanoscale fiber cores are advantageous due to the increased evanescent field power. PMID- 20588794 TI - Spatial filtering technique to image and measure two-dimensional near-forward scattering from single particles. AB - This work describes the design and use of an optical apparatus to measure the far field elastic light-scattering pattern for a single particle over two angular dimensions. A spatial filter composed of a mirror with a small through-hole is used to enable collection of the pattern uncommonly close to the forward direction; to within tenths of a degree. Minor modifications of the design allow for the simultaneous measurement of a particle's image along with its two dimensional scattering pattern. Example measurements are presented involving single micrometer-sized glass spherical particles confined in an electrodynamic trap and a dilute suspension of polystyrene latex particles in water. A small forward-angle technique, called Guinier analysis, is used to determine a particle size estimate directly from the measured pattern without a priori knowledge of the particle refractive index. Comparison of these size estimates to those obtained by fitting the measurements to Mie theory reveals relative errors low as 2%. PMID- 20588795 TI - Photoerasable and photorewritable spatially-tunable laser based on a dye-doped cholesteric liquid crystal with a photoisomerizable chiral dopant. AB - This study investigates, for the first time, a photoerasable and photorewritable spatially-tunable laser using a dye-doped cholesteric liquid crystal (DDCLC) with a photoisomerizable chiral dopant (AzoM). UV illumination via a photomask with a transmittance-gradient can create a pitch gradient in the cell such that the lasing wavelength can be spatially tuned over a wide band of 134nm. The pitch gradient is generated by the UV-irradiation-induced gradient of the cis-AzoM concentration and therefore the induced gradient of the cell HTP value, resulting in the spatial tunability of the laser. Furthermore, the laser has advantages of photoerasability and photorewritability. The spatial tunability of the laser can undergo more than 100 cycles of photoerasing and photorewriting processes without decay or damage. PMID- 20588796 TI - Analysis of the optical properties of wire antennas with displaced terminals. AB - An analysis of the peculiar features of optical wire antennas with displaced terminals is presented. Full-wave simulations and a semianalytical technique based on Pocklington's equation are used in order to systematically study the behavior of input impedance and field enhancement at the antenna terminals when the feed-gap region is shifted with respect to the center of the wire. A simple analytical model based on the evaluation of the effective wavelength of the propagating surface wave is also suggested for the interpretation of the results. PMID- 20588797 TI - Generic real-time uniform K-space sampling method for high-speed swept-source optical coherence tomography. AB - We developed a universal, real-time uniform K-space sampling (Rt-UKSS) method for high-speed swept-source optical coherence tomography (SS-OCT). An external clock uniform in K-space was generated. The clock was synchronized with the zero crossing time of an interferometric calibration signal and used as triggers for a high-speed data acquisition system in a point-by-point fashion, hence enabling uniform data sampling in K-space. Different from the numerical calibration algorithm commonly used in an SS-OCT system, the method reported here does not require over-sampling, thus greatly reducing the demand for digitization, data processing and storage speed. The Rt-UKSS method is adaptive and applicable to a generic SS-OCT system of a wide range of A-scan rates without special adjustment. We successfully implemented the Rt-UKSS method in an SS-OCT system based on a Fourier-domain mode-locked laser (FDML) of a 40-kHz scanning rate. Real-time imaging of biological tissues using such a system was demonstrated with a measured axial resolution of 9.3 mum and detection sensitivity greater than 120dB. PMID- 20588798 TI - Comparative study between conventional and diffusion-bonded Nd-doped vanadate crystals in the passively mode-locked operation. AB - We design a reliable linear three-element cavity to make a comparative study between the conventional and diffusion-bonded Nd:GdVO(4) crystals in the passively mode-locked operation. Experimental investigations reveal that the mode locked pulse width obtained with the diffusion-bonded crystal is considerably broader than that obtained with the conventional crystal, even though the diffusion-bonded crystal can significantly reduce the thermal effects. The pulse broadening is experimentally verified to come from the length of the undoped part that brings in a reduction of the spatial-hole-burning (SHB) effect. PMID- 20588799 TI - 50 fs soliton compression of optical clock pulse recovered from NRZ data injected SOAFL. AB - Mode-locking of semiconductor optical amplifier fiber laser (SOAFL) with 50 fs pulses by extracting the clock of an optical non-return-to-zero (NRZ) data injection is demonstrated. The efficiency of mode-locking in the SOAFL is improved by increasing the seeding power of the large-duty-cycle NRZ data from 3 to 8 dBm into the SOA driven at biased current of 350 mA. After linear dispersion compensation, the mode-locked SOAFL pulsewidth can be further shortened from 20 to 3 ps by increasing the DCF length up to 110 m. By using a booster the EDFA to enlarge the average power of mode-locked SOAFL pulse to 1.3 W, the shortest soliton pulse is occurred after propagating through a 12-m-long SMF. The amplified SOAFL pulse can be compressed to 50 fs after nonlinear compression with its spectral linewidth broadening to 64 nm. Nearly transform-limited time bandwidth product of 0.436 and the maximum pulse compressing ratio of 400 are reported to date. PMID- 20588800 TI - Long-range hybrid network with point and distributed Brillouin sensors using Raman amplification. AB - We propose a novel concept for hybrid networks that combine point and distributed Brillouin sensors in a cost-effective architecture that also deploys remote distributed Raman amplification to extend the sensing range. A 46-km proof-of concept network is experimentally demonstrated integrating point vibration sensors based on fiber Bragg gratings and tapers with distributed temperature sensing along the network bus. In this network the use of Raman amplification to compensate branching and fiber losses provides a temperature resolution of 0.7 degrees C and 13 m. Moreover, it was possible to obtain good optical signal to noise ratio in the measurements from the four point vibration sensors that were remotely multiplexed in the network. These low-cost intensity sensors are able to measure vibrations in the 0.1 to 50 Hz frequency range, which are important in the monitoring of large infrastructures such as pipelines. PMID- 20588801 TI - Estimation of water vapor content in near-infrared bands around 1 mum from MODIS data by using RM-NN. AB - An algorithm based on the radiance transfer model (RM) and a dynamic learning neural network (NN) for estimating water vapor content from moderate resolution imaging spectrometer (MODIS) 1B data is developed in this paper. The MODTRAN4 is used to simulate the sun-surface-sensor process with different conditions. The dynamic learning neural network is used to estimate water vapor content. Analysis of the simulation data indicates that the mean and standard deviation of estimation error are under 0.06 gcm(-2 )and 0.08 gcm(-2). The comparison analysis indicates that the estimation result by RM-NN is comparable to that of a MODIS water vapor content product (MYD05_L2). Finally, validation with ground measurement data shows that RM-NN can be used to accurately estimate the water vapor content from MODIS 1B data, and the mean and standard deviation of the estimation error are about 0.12 gcm(-2 )and 0.18 gcm(-2). PMID- 20588802 TI - Image quality improvement of parallel four-step phase-shifting digital holography by using the algorithm of parallel two-step phase-shifting digital holography. AB - We propose an algorithm that can improve the quality of the reconstructed image from the single hologram recorded by the optical system of the parallel four-step phase-shifting digital holography. The proposed algorithm applies the image reconstruction algorithm of parallel two-step phase-shifting digital holography to the hologram so as to reduce errors in the reconstructed image and eliminate ghosts. We numerically and experimentally confirmed that the proposed algorithm decreased 25% in terms of root mean square error in amplitude, and eliminated the ghosts, respectively. PMID- 20588803 TI - A multi-functional plasmonic biosensor. AB - We present a coupler-free, multi-mode refractive index sensor based on nanostructured split ring resonators (SRRs). The fabricated SRR structures exhibit multiple reflectance peaks, whose spectral positions are sensitive to local dielectric environment and can be quantitatively described by our standing wave plasmonic resonance model, providing a design rule for this multi-mode refractive-index (MMRI) sensor. We further manifest that the lower-order modes possess greater sensitivity associated with stronger localized electromagnetic field leading to shorter detection lengths within five hundreds nanometers, while the higher-order modes present mediate sensitivity with micron-scale detection lengths to allow intracellular bio-events detection. These unique merits enable the SRR-based sensor a multi-functional biosensor and a potential label-free imaging device. PMID- 20588804 TI - High-order rational harmonic mode-locking and pulse-amplitude equalization of SOAFL via reshaped gain-switching FPLD pulse injection. AB - The 40-GHz rational harmonic mode-locking (RHML) and pulse-amplitude equalization of a semiconductor optical amplifier based fiber-ring laser (SOAFL) is demonstrated by the injection of a reshaped 10-GHz gain-switching FPLD pulse. A nonlinearly biased Mach-Zehnder modulator (MZM) is employed to detune the shape of the double-peak pulse before injecting the SOA, such that a pulse-amplitude equalized 4th-order RHML-SOAFL can be achieved by reshaping the SOA gain within one modulation period. An optical injection mode-locking model is constructed to simulate the compensation of uneven amplitudes between adjacent RHML pulse peaks before and after pulse-amplitude equalization. The indirect gain compensation technique greatly suppresses the clock amplitude jitter from 45% to 3.5% when achieving 4th-order RHML, and the amplitude fluctuation of sub-rational harmonic modulating envelope is attenuated by 45 dB. After pulse-amplitude equalization, the pulsewidth of the optical-injection RHML-SOAFL is 8 ps, which still obeys the trend predicted by the inverse square root of repetition rate. The phase noise contributed by the residual ASE noise of the RHML-SOAFL is significantly decreased from -84 to -90 dBc/Hz after initiating the pulse-amplitude equalization, corresponding to the timing jitter reduction from 0.5 to 0.28 ps. PMID- 20588805 TI - Calculating the fine structure of a Fabry-Perot resonator using spheroidal wave functions. AB - A new set of vector solutions to Maxwell's equations based on solutions to the wave equation in spheroidal coordinates allows laser beams to be described beyond the paraxial approximation. Using these solutions allows us to calculate the complete first-order corrections in the short-wavelength limit to eigenmodes and eigenfrequencies in a Fabry-Perot resonator with perfectly conducting mirrors. Experimentally relevant effects are predicted. Modes which are degenerate according to the paraxial approximation are split according to their total angular momentum. This includes a splitting due to coupling between orbital angular momentum and spin angular momentum. PMID- 20588806 TI - Stochastic BER estimation for coherent QPSK transmission systems with digital carrier phase recovery. AB - We propose a stochastic bit error ratio estimation approach based on a statistical analysis of the retrieved signal phase for coherent optical QPSK systems with digital carrier phase recovery. A family of the generalized exponential function is applied to fit the probability density function of the signal samples. The method provides reasonable performance estimation in presence of both linear and nonlinear transmission impairments while reduces the computational intensity greatly compared to Monte Carlo simulation. PMID- 20588807 TI - Quantum key distribution on a 10Gb/s WDM-PON. AB - We present the first demonstration of quantum key distribution (QKD) on a multi user wavelength division multiplexed passive optical network (WDM-PON) with simultaneous, bidirectional 10Gb/s classical channel transmission. The C-Band QKD system operates at a clock rate of 10GHz and employs differential phase shift keying (DPSK). A dual feeder fiber and band filtering scheme is used to suppress classical to quantum channel cross-talk generated by spontaneous Raman scattering, which would otherwise prevent secure key distribution. Quantum keys were distributed to 4 users with negligible Raman cross-talk penalties. The mean QBER value for 4 users was 3.5% with a mean raw key distribution rate of 1.3Mb/s, which decreased to 696kb/s after temporal windowing to reduce inter-symbol interference due to single photon detector timing jitter. PMID- 20588808 TI - Study of cross-phase modulation and free-carrier dispersion in silicon photonic wires for Mamyshev signal regenerators. AB - A numerical study on Mamyshev signal regeneration realized on silicon photonic wires is reported. Unlike fiber-optics Mamyshev regenerators employing cross phase modulation, silicon photonic wires have to include two-photon absorption and the two-photon-absorption-induced free-carrier effect. By well adjusting time delay between the co-propagating signal and clock pulses, both cross-phase modulation and free-carrier dispersion could induce nonlinear wavelength shift, which is essential for signal recovery in the Mamyshev regeneration scheme. A simulation result shows the quality factor of signal eye diagram improved by more than 4 dB for Return-to-Zero signals with pulse width 10 ps, peak power 6.5 W, and operation speed 10 Gbit/s through a 1-cm silicon photonic wire. PMID- 20588809 TI - Influence of UV illumination on the cold temperature operation of a LiNbO(3) Q switched Nd:YAG laser. AB - UV illumination of a lithium niobate Q-switch was demonstrated as an effective means to eliminate a loss in hold-off and associated prelasing that occurs under cold temperature operation of Q-switched lasers. This degradation occurs due to the pyroelectric effect, where an accumulation of charge on crystal faces results in a reduction in the Q-switch hold-off and a spatially variable loss of the Q switch in its high-transmission state, both resulting in lowering of the maximum Q-switched pulse energy. With UV illumination, the resulting creation of photo generated carriers was shown to be effective in eliminating both of these effects. A Q-switched Nd:YAG laser utilizing UV-illuminated LiNbO(3) was shown to operate under cold temperatures without prelasing or spatially variable loss. PMID- 20588810 TI - Nonlinear spectra of ZnO: reverse saturable, two- and three-photon absorption. AB - We present a broadband (460 - 980 nm) analysis of the nonlinear absorption processes in bulk ZnO, a large-bandgap material with potential blue-to-UV photonic device applications. Using an optical parametric amplifier we generated tunable 1-kHz repetition rate laser pulses and employed the Z-scan technique to investigate the nonlinear absorption spectrum of ZnO. For excitation wavelengths below 500 nm, we observed reverse saturable absorption due to one-photon excitation of the sample, agreeing with rate-equation modeling. Two- and three photon absorption were observed from 540 to 980 nm. We also determined the spectral regions exhibiting mixture of nonlinear absorption mechanisms, which were confirmed by photoluminescence measurements. PMID- 20588811 TI - Array size scalability of passively coherently phased fiber laser arrays. AB - We explore, by means of experiments and simulation, the power combining efficiency and power fluctuation of coherently phased 2, 4, 6, 8, 10, 12, 14, 16 channel fiber-laser arrays using fused 50:50 single-mode couplers. The measured evolution of power combining efficiency with array size agrees with simulations based on a new propagation model. For our particular system the power fluctuations due to small wavelength-scale length variations are seen to scale with array size as N(3). Beat spectra support the notion that a lack of coherently-combined supermodes in arrays of increasing size leads to a decrease in combined-power efficiency. PMID- 20588812 TI - Superfocusing terahertz waves below lambda/250 using plasmonic parallel-plate waveguides. AB - We experimentally demonstrate complete two-dimensional (2-D) confinement of terahertz (THz) energy in finite-width parallel-plate waveguides, defying conventional wisdom in the century-old field of microwave waveguide technology. We find that the degree of energy confinement increases exponentially with decreasing plate separation. We propose that this 2-D confinement is mediated by the mutual coupling of plasmonic edge modes, analogous to that observed in slot waveguides at optical wavelengths. By adiabatically tapering the width and the separation, we focus THz waves down to a size of 10 microm (approximately lambda/260) by 18 microm ( approximately lambda/145), which corresponds to a mode area of only 2.6 x 10(-5) lambda(2). PMID- 20588813 TI - Optically switchable, rapidly relaxing cholesteric liquid crystal reflectors. AB - Reversible, fast, all-optical switching of the reflection of a cholesteric liquid crystal (CLC) is demonstrated in a formulation doped with push-pull azobenzene dyes. The reflection of the photosensitive CLC compositions is optically switched by exposure to 488 and 532 nm CW lasers as well as ns pulsed 532 nm irradiation. Laser-directed optical switching of the reflection of the CLC compositions occurs rapidly, within a few hundred milliseconds for the CW laser lines examined here. Also observed is optical switching on the order of tens of nanoseconds when the CLC is exposed to a single nanosecond pulse with 0.2 J/cm(2) energy density. The rapid cis-trans isomerization typical of push-pull azobenzene dye is used for the first time to rapidly restore the reflection of the CLC from a photoinduced isotropic state within seconds after cessation of light exposure. PMID- 20588814 TI - Generation of terahertz radiation from ionizing two-color laser pulses in Ar filled metallic hollow waveguides. AB - The generation of THz radiation from ionizing two-color femtosecond pulses propagating in metallic hollow waveguides filled with Ar is numerically studied. We observe a strong reshaping of the low-frequency part of the spectrum. More precisely, after several millimeters of propagation the spectrum is extended from hundreds of GHz up to approximately 150 THz. For longer propagation distances, nearly single-cycle near-infrared pulses with wavelengths around 4.5 microm are obtained by appropriate spectral filtering, with an efficiency of 0.1-1%. PMID- 20588815 TI - Demonstration of ultra-wideband (UWB) over fiber based on optical pulse-injected semiconductor laser. AB - We experimentally demonstrated the ultra-wideband (UWB) signal generation utilizing nonlinear dynamics of an optical pulse-injected semiconductor laser. The UWB signals generated are fully in compliant with the FCC mask for indoor radiation, while a large fractional bandwidth of 93% is achieved. To show the feasibility of UWB-over-fiber, transmission over a 2 km single-mode fiber and a wireless channel utilizing a pair of broadband antennas are examined. Moreover, proof of concept experiment on data encoding and decoding with 250 Mb/s in the optical pulse-injected laser is successfully demonstrated. PMID- 20588816 TI - Efficient broadband near-infrared quantum cutting for solar cells. AB - Yb(2+) and Yb(3+) co-activated luminescent material that can cut one photon in ultraviolet and visible region into multi NIR photons could be used as a downconversion luminescent convertor in front of crystalline silicon solar cell panels to reduce thermalization loss of the solar cell. After a direct excitation of Yb(2+) ions, an intense Yb(3+) luminescence is observed based on a cooperative energy transfer process. The energy transfer process is discussed according to the dependence of Yb(3+) luminescence intensity on the excitation power and the ambient temperature. PMID- 20588817 TI - Enhanced spontaneous light emission by multiple surface plasmon coupling. AB - Photoluminescence of polyfluoren copolymers, a white-light material, was demonstrated to be enhanced selectively by coupling with either localized or propagating modes of surface plasmon resonance (SPR). The silver sub-micron cylinders with 75nm height fabricated by e-beam lithography followed by e-beam evaporation and lift-off process. The enhanced light emissions at 500nm and 533nm are attributed to the low frequency branch of localized SPR. Furthermore, a 50nm silver thin film between these cylinders and the substrate provides propagating surface plasmons under excitation and enhances the blue emission band of the polyfluoren copolymer at 438nm. This delocalized SPR is sufficient for effective plasmon to light conversion. Moreover, by effectively coupling the localized and propagating SPR, we can experimentally demonstrate that the photoluminescence of polyfluoren copolymers is enhanced by 4 to 5.4 times at different wavelengths compared to enhancement by either single mode. PMID- 20588818 TI - Superfast phase-shifting method for 3-D shape measurement. AB - Recently introduced DLP Discovery technology allows for tens of kHz binary image switching, which has great potential for superfast 3-D shape measurement. This paper presents a system that realizes 3-D shape measurement by using a DLP Discovery technology to switch binary structured patterns at very high frame rates. The sinusoidal fringe patterns are generated by properly defocusing the projector. Combining this approach with a phase-shifting method, we achieve an unprecedented rate for 3-D shape measurement: 667 Hz. This technology can be applied to numerous applications including medical science, biometrics, and entertainment. PMID- 20588820 TI - A 113 fs fiber laser operating at 1.56 mum using a cascadable film-type saturable absorber with P3HT-incorporated single-wall carbon nanotubes coated on polyamide. AB - We successfully fabricated a cascadable film-type single-wall carbon nanotube (SWNT) saturable absorber coated on aromatic polyamide film, in which the saturable absorption effect can be controlled with the number of films. A conductive polymer P3HT (poly-3-hexylthiophene) was adopted to obtain a uniform SWNT solution. We applied saturable absorber films to a passively mode-locked fiber laser and successfully generated a 113 fs, 42 MHz pulse by inserting two film layers between fiber connectors in the cavity. PMID- 20588819 TI - Multi-angle lensless digital holography for depth resolved imaging on a chip. AB - A multi-angle lensfree holographic imaging platform that can accurately characterize both the axial and lateral positions of cells located within multi layered micro-channels is introduced. In this platform, lensfree digital holograms of the micro-objects on the chip are recorded at different illumination angles using partially coherent illumination. These digital holograms start to shift laterally on the sensor plane as the illumination angle of the source is tilted. Since the exact amount of this lateral shift of each object hologram can be calculated with an accuracy that beats the diffraction limit of light, the height of each cell from the substrate can be determined over a large field of view without the use of any lenses. We demonstrate the proof of concept of this multi-angle lensless imaging platform by using light emitting diodes to characterize various sized microparticles located on a chip with sub-micron axial and lateral localization over approximately 60 mm(2) field of view. Furthermore, we successfully apply this lensless imaging approach to simultaneously characterize blood samples located at multi-layered micro-channels in terms of the counts, individual thicknesses and the volumes of the cells at each layer. Because this platform does not require any lenses, lasers or other bulky optical/mechanical components, it provides a compact and high-throughput alternative to conventional approaches for cytometry and diagnostics applications involving lab on a chip systems. PMID- 20588821 TI - Observation of enhanced transmission for s-polarized light through a subwavelength slit. AB - Enhanced optical transmission (EOT) through a single aperture is usually achieved by exciting surface plasmon polaritons with periodic grooves. Surface plasmon polaritons are only excited by p-polarized incident light, i.e. with the electric field perpendicular to the direction of the grooves. The present study experimentally investigates EOT for s-polarized light. A subwavelength slit surrounded on each side by periodic grooves has been fabricated in a gold film and covered by a thin dielectric layer. The excitation of s-polarized dielectric waveguide modes inside the dielectric film strongly increases the s-polarized transmission. A 25 fold increase is measured as compared to the case without the dielectric film. Transmission measurements are compared with a coupled mode method and show good qualitative agreement. Adding a waveguide can improve light transmission through subwavelength apertures, as both s and p-polarization can be efficiently transmitted. PMID- 20588822 TI - Enhanced light extraction of nonpolar a-plane (11-20) GaN light emitting diodes on sapphire substrates by photo-enhanced chemical wet etching. AB - The extraction efficiency of nonpolar a-plane (11-20) GaN LEDs on sapphire substrates has been enhanced by selectively etching the mesa sidewall faces and the n-type GaN surfaces with photoenhanced chemical wet etching. Submicron-sized trigonal prisms having prismatic planes of {1-100} were clearly displayed on the n-type GaN surfaces as well as the sidewall face after 5 min etching at 60 degrees C. The radiation patterns have shown that more light is extracted in all directions and the output powers of surface textured a-plane GaN LEDs have increased by 25% compared with control samples. PEC wet etching produced unique feature of etching morphology on the mesa sidewall faces and the n-type GaN surface. PMID- 20588823 TI - The PDMS-based microfluidic channel fabricated by synchrotron radiation stimulated etching. AB - Micro pattern on PDMS surface has been achieved by using synchrotron radiation (SR) stimulated etching. The experimental results indicated that SR stimulated etching has many advantages, such as extremely high etching rate (as large as 40 50 mum per 10 min), area-selectivity and anisotropy at room temperature, high spatial resolution. Combining the SR stimulated etching with photolithography, a PDMS-based microfluidic channel was obtained. The aim of this work is to develop a three-dimensional microfluidic channel with a special through hole, which is beneficial for cell differentiation, functionality and longevity and cannot be fabricated by conventional direct tooling techniques. PMID- 20588824 TI - Simple piezoelectric-actuated mirror with 180 kHz servo bandwidth. AB - We present a high bandwidth piezoelectric-actuated mirror for length stabilization of an optical cavity. The actuator displays a transfer function with a flat amplitude response and greater than 135 masculine phase margin up to 200 kHz, allowing a 180 kHz unity gain frequency to be achieved in a closed servo loop. To the best of our knowledge, this actuator has achieved the largest servo bandwidth for a piezoelectric transducer (PZT). The actuator should be very useful in a wide variety of applications requiring precision control of optical lengths, including laser frequency stabilization, optical interferometers, and optical communications. PMID- 20588825 TI - Novel auto-correction method in a fiber-optic distributed-temperature sensor using reflected anti-Stokes Raman scattering. AB - A novel method for auto-correction of fiber optic distributed temperature sensor using anti-Stokes Raman back-scattering and its reflected signal is presented. This method processes two parts of measured signal. One part is the normal back scattered anti-Stokes signal and the other part is the reflected signal which eliminate not only the effect of local losses due to the micro-bending or damages on fiber but also the differential attenuation. Because the beams of the same wavelength are used to cancel out the local variance in transmission medium there is no differential attenuation inherently. The auto correction concept was verified by the bending experiment on different bending points. PMID- 20588826 TI - Double-clad fiber coupler for endoscopy. AB - We present a double-clad fiber coupler (DCFC) for use in endoscopy to reduce speckle contrast, increase signal collection and depth of field. The DCFC is made by fusing and tapering two all silica double-clad fiber (DCF) and allows achromatic transmission of >95% of core illumination (1265nm - 1325nm) as well as collection of >42% of inner cladding diffuse light. Its potential for endoscopy is demonstrated in a spectrally encoded imaging setup which shows speckle reduction by a factor 5, increased signal collection by a factor 9 and enhanced depth of field by 1.8 times. Separation by the DCFC of single- and multi-mode signals allows combining low-speckle reflectance images (25.5 fps) with interferometrically measured depth profiles (post-processed) for of small three dimensional (3D) features through an all-fiber low loss instrument. PMID- 20588827 TI - The correlation confocal microscope. AB - A new type of confocal microscope is described which makes use of intensity correlations between spatially correlated beams of light. It is shown that this apparatus leads to significantly improved transverse resolution. PMID- 20588828 TI - Plasmonic resonances in optomagnetic metamaterials based on double dot arrays. AB - We study optical properties of optomagnetic metamaterials produced by regular arrays of double gold dots (nanopillars). Using combined data of spectroscopic ellipsometry, transmission and reflection measurements, we identify localized plasmon resonances of a nanopillar pair and measure their dependences on dot sizes. We formulate the necessary condition at which an effective field theory can be applied to describe optical properties of a composite medium and employ interferometry to measure phase shifts for our samples. A negative phase shift for transmitted green light coupled to an antisymmetric magnetic mode of a double dot array is observed. PMID- 20588829 TI - Wavelength reused bidirectional transmission of adaptively modulated optical OFDM signals in WDM-PONs incorporating SOA and RSOA intensity modulators. AB - Detailed numerical investigations are undertaken of wavelength reused bidirectional transmission of adaptively modulated optical OFDM (AMOOFDM) signals over a single SMF in a colorless WDM-PON incorporating a semiconductor optical amplifier (SOA) intensity modulator and a reflective SOA (RSOA) intensity modulator in the optical line termination and optical network unit, respectively. A comprehensive theoretical model describing the performance of such network scenarios is, for the first time, developed, taking into account dynamic optical characteristics of SOA and RSOA intensity modulators as well as the effects of Rayleigh backscattering (RB) and residual downstream signal-induced crosstalk. The developed model is rigorously verified experimentally in RSOA-based real-time end-to-end OOFDM systems at 7.5 Gb/s. It is shown that the RB noise and crosstalk effects are dominant factors limiting the maximum achievable downstream and upstream transmission performance. Under optimum SOA and RSOA operating conditions as well as practical downstream and upstream optical launch powers, 10 Gb/s downstream and 6 Gb/s upstream over 40 km SMF transmissions of conventional double sideband AMOOFDM signals are feasible without utilizing in-line optical amplification and chromatic dispersion compensation. In particular, the aforementioned transmission performance can be improved to 23 Gb/s downstream and 8 Gb/s upstream over 40 km SMFs when single sideband subcarrier modulation is adopted in the downstream systems. PMID- 20588830 TI - Broadband all-optical modulation in hydrogenated-amorphous silicon waveguides. AB - We demonstrate broadband all-optical modulation in low loss hydrogenated amorphous silicon (a-Si:H) waveguides. Significant modulation (approximately 3 dB) occurs with a device of only 15 microm without the need for cavity interference effects in stark contrast to an identical crystalline silicon waveguide. We attribute the enhanced modulation to the significantly larger free carrier absorption effect of a-Si:H, estimated here to be alpha = 1.6310(-16)N cm(-1). In addition, we measured the modulation time to be only tau(c) approximately 400 ps, which is comparable to the recombination rate measured in sub-micron crystalline silicon waveguides, illustrating the strong dominance of surface recombination in similar sized (460 nm x 250 nm) a-Si:H waveguides. Consequently, a-Si:H could serve as a high performance platform for backend integrated CMOS photonics. PMID- 20588831 TI - Optimization and performance criteria of a Stokes polarimeter based on two variable retarders. AB - In this paper we present the analysis, optimization and implementation of several Stokes polarimeter configurations based on a set-up including two variable retarders. The polarimeter analysis is based on the Mueller-Stokes formalism, and as a consequence, it is suitable to deal with depolarized light. Complete Stokes polarimeters are optimized by minimizing the amplification of simulated errors into the final solution. Different indicators useful to achieve this aim, as the condition number or the equally weighted variance, are compared in this paper. Moreover, some of the optimized polarimeters are experimentally implemented and it is studied the influence of small deviations from the theoretical ones on the amplification of the Stokes component error. In addition, the benefit of using incomplete polarimeters, when detecting specific ranges of states of polarization, is discussed. PMID- 20588832 TI - Downhill simplex algorithm based approach to holey fiber design for tunable fiber parametric wavelength converters. AB - We present a new approach to the design of the holey fibers that have ultra-high nonlinearity and dispersion properties optimized for tunable fiber parametric wavelength converters based on degenerated four wave mixing. This hybrid approach combines downhill simplex algorithms with four wave mixing modeling. Exploiting the relations between fiber properties and the converter's characteristics, this method is not only much faster than other methods proposed before but also enables an inverse design of the holey fibers according to the pre-set device characteristics, like conversion gain, tuning range, fiber length and pump power. We then investigate the sensitivity of these characteristics to the small variations in the fiber structural parameters and find adjusting the pump power can to some extent mitigate the impact of the fabrication errors. PMID- 20588833 TI - Label-free second harmonic generation holographic microscopy of biological specimens. AB - Second-order nonlinear holographic microscopy for high-speed, three-dimensional imaging is demonstrated. The use of harmonic generation allows image formation of endogenous features in biological samples such as muscle tissue. We have acquired holograms with acquisition times as short as 10 ms, limited by the switching speed of our shutter; frame rates of 100's of Hz are expected to be possible. The samples are imaged with a Yb:KGW femtosecond laser oscillator, whose 1027 nm wavelength is well suited to minimize absorption and scattering. The low average power of the oscillator prevents damage to the sample. PMID- 20588834 TI - Low power and compact reconfigurable multiplexing devices based on silicon microring resonators. AB - We present thermally reconfigurable multiplexing devices based on silicon microring resonators with low tuning power and low thermal crosstalk. Micro heaters on top of the rings are employed to tune the resonant wavelengths through the thermo-optic effect of silicon. We achieve a low tuning power of 21 mW per free spectral range for a single ring by exploiting thermal isolation trenches close to the ring waveguides. Negligible thermal crosstalk is demonstrated for rings spaced by 15 microm, enabling compact multiplexing devices. The tuning time constant is demonstrated to be less than 10 micros. PMID- 20588835 TI - Impact of various noises on maximum reach in broadband light source based high capacity WDM passive optical networks. AB - We investigated the effects of various noises on the performance of extended reach WDM-PONs based on broadband light sources (BLSs). The maximum reach in BLS based WDM-PONs was analyzed by taking into account the impact of relative intensity noise of optical source, chromatic dispersion of transmission fiber and in-band crosstalk. We confirmed that the system's performance of BLS based WDM PONs would be strongly dependent on the equivalent optical bandwidth of optical source. From the results, we found that the maximum reach in BLS based WDM-PONs operating at 1.25 Gb/s could be increased to be approximately 70 km of single mode fiber as long as the chirp and relative intensity noise (RIN) of optical source would be suppressed properly. PMID- 20588836 TI - The projection approximation and edge contrast for x-ray propagation-based phase contrast imaging of a cylindrical edge. AB - We examine the projection approximation in the context of propagation-based phase contrast imaging using hard x-rays. Specifically, we consider the case of a cylinder or a rounded edge, as a simple model for the edges of many biological samples. The Argand-plane signature of a propagation-based phase contrast fringe from the edge of a cylinder is studied, and the evolution of this signature with propagation. This, along with experimental images obtained using a synchrotron source, reveals how propagation within the scattering volume is not fully described in the projection approximation's ray-based approach. This means that phase contrast fringes are underestimated by the projection approximation at a short object-to-detector propagation distance, namely a distance comparable to the free-space propagation within the volume. This failure of the projection approximation may become non-negligible in the detailed study of small anatomical features deep within a large body. Nevertheless, the projection approximation matches the exact solution for a larger propagation distance typical of those used in biomedical phase contrast imaging. PMID- 20588838 TI - Time domain spectral phase encoding/DPSK data modulation using single phase modulator for OCDMA application. AB - A novel scheme using single phase modulator for simultaneous time domain spectral phase encoding (SPE) signal generation and DPSK data modulation is proposed and experimentally demonstrated. Array- Waveguide-Grating and Variable-Bandwidth Spectrum-Shaper based devices can be used for decoding the signal directly in spectral domain. The effects of fiber dispersion, light pulse width and timing error on the coding performance have been investigated by simulation and verified in experiment. In the experiment, SPE signal with 8-chip, 20GHz/chip optical code patterns has been generated and modulated with 2.5 Gbps DPSK data using single modulator. Transmission of the 2.5 Gbps data over 34km fiber with BER<10(-9) has been demonstrated successfully. The proposed scheme has simple configuration and improved flexibility that can significantly improve the data confidentiality for optical code division multiple access (OCDMA) and secure optical communication applications. PMID- 20588840 TI - OOK generation based on MZI incorporating a pumped nonlinear ring resonators system. AB - In this paper, we present an interesting result of nonlinear light pulse propagation within a Mach-Zehnder Inteferometer (MZI) which can be used to extend the existed on off keying (OOK) techniques. The goal of this paper is OOK generation based on MZI incorporating a pumped nonlinear ring resonators system. We first analyze the principles of a phase modulation scheme using MZI incorporating the triple nonlinear ring resonators, which can be fabricated and used in practical communications. After that, we focus on the recent modulation schemes, where the all-optical on off keying and the phase shift control for phase shaped binary transmission (PSBT) are discussed in details. The novelty of this work is that the nonlinear ring resonators are used incorporating a MZI, where the extended switching generation can be achieved and seen. PMID- 20588842 TI - Gain competition in dual wavelength quantum cascade lasers. AB - We investigated dual wavelength mid-infrared quantum cascade lasers based on heterogeneous cascades. We found that due to gain competition laser action tends to start in higher order lateral modes. The mid-infrared mode with the lower threshold current reduces population inversion for the second laser with the higher threshold current due to stimulated emission. We developed a rate equation model to quantitatively describe mode interactions due to mutual gain depletion. PMID- 20588843 TI - Emission properties and photon statistics of a single quantum dot laser. AB - A theoretical description for a single quantum-dot emitter in a microcavity is developed.We analyze for increasing steady-state pump rate the transition from the strong-coupling regime with photon antibunching to the weak-coupling regime with coherent emission. It is demonstrated how Coulomb interaction of excited carriers and excitation-induced dephasing can strongly modify the emission properties. Our theoretical investigations are based on a direct solution of the Liouville-von Neumann equation for the coupled carrier-photon system. We include multiple carrier excitations in the quantum dot, their Coulomb interaction, as well as excitation-induced dephasing and screening. Similarities and differences to atomic systems are discussed and results in the regime of recent experiments are interpreted. PMID- 20588844 TI - Performance analysis of incoherent multi-wavelength OCDMA systems under the impact of four-wave mixing. AB - In this paper, we comprehensively analyze the impact of four wave mixing (FWM) on the performance of incoherent multi-wavelength optical code-division multiple access (MW-OCDMA) systems. We also consider many other interferences and noises, including multiple access interference, optical beating interference, and receiver noise, in the analysis. From the numerical results, we can find the power ranges of different MW-OCDMA systems, in which the impact of FWM is dominant and consequently results in an increase in the bit-error rate of the systems. We also find that the impact of FWM becomes more severe when the frequency spacing is small and/or dispersion-shifted fiber is used. In addition, we quantitatively discuss the impact of FWM on the number of supportable users and power penalty in the MW-OCDMA systems. PMID- 20588846 TI - Sonification of optical coherence tomography data and images. AB - Sonification is the process of representing data as non-speech audio signals. In this manuscript, we describe the auditory presentation of OCT data and images. OCT acquisition rates frequently exceed our ability to visually analyze image based data, and multi-sensory input may therefore facilitate rapid interpretation. This conversion will be especially valuable in time-sensitive surgical or diagnostic procedures. In these scenarios, auditory feedback can complement visual data without requiring the surgeon to constantly monitor the screen, or provide additional feedback in non-imaging procedures such as guided needle biopsies which use only axial-scan data. In this paper we present techniques to translate OCT data and images into sound based on the spatial and spatial frequency properties of the OCT data. Results obtained from parameter mapped sonification of human adipose and tumor tissues are presented, indicating that audio feedback of OCT data may be useful for the interpretation of OCT images. PMID- 20588848 TI - Tunable liquid-filled lens integrated with aspherical surface for spherical aberration compensation. AB - A novel liquid-filled lens design is presented. During fabrication, high precision single point diamond turning (SPDT) is introduced into standard soft lithography process to fabricate an aspherical surface constituting one end of lens. This enables the spherical aberration associated with the operation of the conventional liquid-filled lenses to be compensated for. Through flexibly optimizing this surface contour, it can be designed to work within particular working regions with improved optical quality. At the same time, the deformable elastic membrane is still adopted at the other end of the lens, thus preserving the high focal length tunability. This proof of concept and the performance of the proposed lens have been demonstrated using the lateral shearing interferometry experiment.. PMID- 20588849 TI - Fast calculation of computer-generated-hologram on AMD HD5000 series GPU and OpenCL. AB - In this paper, we report fast calculation of a computer-generated-hologram using a new architecture of the HD5000 series GPU (RV870) made by AMD and its new software development environment, OpenCL. Using a RV870 GPU and OpenCL, we can calculate 1,920 x 1,024 resolution of a CGH from a 3D object consisting of 1,024 points in 30 milli-seconds. The calculation speed realizes a speed approximately two times faster than that of a GPU made by NVIDIA. PMID- 20588850 TI - 640 Gbit/s and 1.28 Tbit/s polarisation insensitive all optical wavelength conversion. AB - We report the first demonstration of polarisation insensitive all-optical wavelength conversion (AOWC) for single wavelength channel 640 Gbit/s return-to zero differential-phase-shift-keying (RZ-DPSK) signal and 1.28 Tbit/s polarisation multiplexed (Pol-Mux) RZ-DPSK signals using a 100-m polarisation maintaining highly nonlinear fiber (PM-HNLF) in a polarisation diversity loop configuration. The AOWC is based on four-wave mixing in PM-HNLF. Error free performance is achieved for the wavelength converted signals. Less than 0.5 dB polarisation sensitivity is obtained. PMID- 20588851 TI - Two-photon interference with a semiconductor integrated source at room temperature. AB - We experimentally demonstrate an integrated semiconductor ridge microcavity source of counterpropagating twin photons at room temperature in the telecom range. Based on type II parametric down conversion with a counterpropagating phase-matching, pump photons generate photon pairs with an efficiency of about 10(-11) and a spectral linewidth of 0.3 nm for a 1 mm long sample. The indistiguishability of the photons of the pair is measured via a Hong-Ou-Mandel two-photon interference experiment showing a visibility of 85 %. This work opens a route towards new guided-wave semiconductor quantum devices. PMID- 20588852 TI - Electronically controlled coherent linear optical sampling for optical coherence tomography. AB - Electronically controlled coherent linear optical sampling for low coherence interferometry (LCI) and optical coherence tomography (OCT) is demonstrated, using two turn-key commercial mode-locked fiber lasers with synchronized repetition rates. This novel technique prevents repetition rate limitations present in previous implementations based on asynchronous optical sampling. Adjustable scanning ranges and scanning rates are realized within an interferometric setup by full electronic control of the mutual time delay of the two laser pulse trains. We implement this novel linear optical sampling scheme with broad spectral bandwidths for LCI, optical filter characterization and OCT imaging in two and three dimensions. PMID- 20588853 TI - Photoacoustic imaging velocimetry for flow-field measurement. AB - We present the photoacoustic imaging velocimetry (PAIV) method for flow-field measurement based on a linear transducer array. The PAIV method is realized by using a Q-switched pulsed laser, a linear transducer array, a parallel data acquisition equipment and dynamic focusing reconstruction. Tracers used to track liquid flow field were real-timely detected, two-dimensional (2-D) flow visualization was successfully reached, and flow parameters were acquired by measuring the movement of the tracer. Experimental results revealed that the PAIV method would be developed into 3-D imaging velocimetry for flow-field measurement, and potentially applied to research the security and targeting efficiency of optical nano-material probes. PMID- 20588854 TI - Light scattering by an array of electric and magnetic nanoparticles. AB - Light scattering by an array of alternating electric and magnetic nanoparticles is analyzed in detailed. Specific geometrical conditions are derived, where such an array behaves like double-negative particles, leading to a suppression of the backscattered intensity. This effect is very robust and could be used to produce double-negative metamaterials using single-negative components. PMID- 20588855 TI - Performance of serial time-encoded amplified microscope. AB - Serial time-encoded amplified microscopy (STEAM) is an entirely new imaging modality that enables ultrafast continuous real-time imaging with high sensitivity. By means of optical image amplification, STEAM overcomes the fundamental tradeoff between sensitivity and speed that affects virtually all optical imaging systems. Unlike the conventional microscope systems, the performance of STEAM depends not only on the lenses, but also on the properties of other components that are unique to STEAM, namely the spatial disperser, the group velocity dispersion element, and the back-end electronic digitizer. In this paper, we present an analysis that shows how these considerations affect the spatial resolution, and how they create a trade-off between the number of pixels and the frame rate of the STEAM imager. We also quantify how STEAM's optical image amplification feature improves the imaging sensitivity. These analyses not only provide valuable insight into the operation of STEAM technology but also serve as a blue print for implementation and optimization of this new imaging technology. PMID- 20588856 TI - Real-time visualization of electromagnetic waves propagating in air using live electro-optic imaging technique. AB - Electromagnetic waves propagating in air are visually observed with phase evolution in real time by live electro-optic imaging technique. We show how geometrical and crystallographic arrangements of an electro-optic sensor plate enable the realization of the real-time visual observation of traveling 100-GHz electromagnetic waves. For this purpose, a generation technique for a 100-GHz optical local oscillator signal at 780 nm was newly developed, whose optical wavelength is suitable for the ultra-parallel RF electric field data acquisition by a Si-CMOS image sensor. PMID- 20588857 TI - Electrically switching transverse modes in high power THz quantum cascade lasers. AB - The design and fabrication of a high power THz quantum cascade laser (QCL), with electrically controllable transverse mode is presented. The switching of the beam pattern results in dynamic beam switching using a symmetric side current injection scheme. The angular-resolved L-I curves measurements, near-field and far-field patterns and angular-resolved lasing spectra are presented. The measurement results confirm that the quasi-TM(01) transverse mode lases first and dominates the lasing operation at lower current injection, while the quasi-TM(00) mode lases at a higher threshold current density and becomes dominant at high current injection. The near-field and far-field measurements confirm that the lasing THz beam is maneuvered by 25 degrees in emission angle, when the current density changes from 1.9 kA/cm(2) to 2.3 kA/cm(2). A two-dimension (2D) current and mode calculation provides a simple model to explain the behavior of each mode under different bias conditions. PMID- 20588858 TI - Passively Q-switched erbium all-fiber lasers by use of thulium-doped saturable absorber fibers. AB - We demonstrate all-fiber passively Q-switched erbium lasers at 1570 nm using Tm(3+)-doped saturable-absorber fibers. The absorption cross section of a Tm(3+) doped fiber at 1570 nm was measured in a bleaching experiment to be about 1.44 x 10(-20) cm(2). With a thulium-doped fiber, sequential pulses with a pulse energy of 9 microJ and a pulse duration of about 420 ns were stably produced at repetition rates in the range 0.1 to 2 kHz. The maximum pulse repetition rate was 6 kHz, limited by the maximum pump power of a 980-nm laser diode, about 230 mW. PMID- 20588859 TI - Brillouin spectroscopy of YAG-derived optical fibers. AB - We present Brillouin spectroscopy of YAG-derived optical fibers. It is found that the addition of yttria and alumina both tend to raise the acoustic velocity when added to silica, with the change due to yttria being much weaker. The temperature dependence of the Stokes's shift in the YAG-derived fibers is also measured, disclosing a lesser temperature dependence than conventional Ge-doped fibers. These fibers are found experimentally to have a substantially larger acoustic attenuation coefficient relative to that of bulk silica, and assuming a photoelastic constant of amorphous YAG similar to that of pure crystalline YAG, a much-reduced Brillouin gain coefficient as a result. A 40 weight percent yttria and alumina fiber has a Brillouin gain coefficient estimated to be roughly one sixth of pure silica. We also show that the addition of Er to the YAG-derived system decreases the acoustic velocity and broadens the Brillouin spectrum. PMID- 20588860 TI - Laminar optical tomography of the hemodynamic response in the lumbar spinal cord of rats. AB - Intrinsic optical imaging (IOI) has emerged as a very powerful tool to assess neuronal function in small animals. Although it has been used extensively in the brain, its application to the spinal cord is rare. The inability of intrinsic optical techniques to resolve different depths and embedded gray matter hampers their capacity to distinguish larger vasculature contributions of hemodynamic signals originating from motoneuron and interneuron activation. Laminar optical tomography (LOT) is a recently-developed method that fills the gap left between IOI and diffuse optical imaging. With distinct source-detector separations, light that propagates deeper into tissues can be distinguished from light originating from the surface, providing depth sensitivity. In this work, LOT is investigated for the first time to image spinal cord activation with simultaneous IOI of the cortex in rats. Such proof of concept provides a powerful imaging modality to study spinal cord activation and disruption after injury. PMID- 20588861 TI - The origin of enhanced optical absorption in solar cells with metal nanoparticles embedded in the active layer. AB - We analyze the enhancement in optical absorption of an absorbing medium when spherical metal nanoparticles are embedded in it. Our analysis uses generalized Mie theory to calculate the absorbed optical power as a function of the distance from the metal nanoparticle. This analysis is used to evaluate the potential of enhancing optical absorption in thin-film solar cells by embedding spherical metal nanoparticles. We consider the trade-off between maximizing overall optical absorption and ensuring that a large fraction of the incident optical power is dissipated in the absorbing host medium rather than in the metal nanoparticle. We show that enhanced optical absorption results from strong scattering by the metal nanoparticle which locally enhances the optical electric fields. We also discuss the effect of a thin dielectric encapsulation of the metal nanoparticles. PMID- 20588862 TI - Experimental demonstration of a synthetic aperture compression scheme for multi Petawatt high-energy lasers. AB - We present the experimental demonstration of a subaperture compression scheme achieved in the PETAL (PETawatt Aquitaine Laser) facility. We evidence that by dividing the beam into small subapertures fitting the available grating size, the sub-beam can be individually compressed below 1 ps, synchronized below 50 fs and then coherently added thanks to a segmented mirror. PMID- 20588863 TI - 80-fs Nd:silicate glass laser pumped by a single-mode 200-mW diode. AB - A Nd(3+)-doped Schott LG680 silicate glass laser was pumped with a single-mode 200-mW diode. Efficient cw operation was demonstrated with 37.5 mW output power and 36% slope efficiency. Passive mode-locking with a semiconductor saturable absorber mirror yielded 80-fs pulses with a two-prism setup. Alternatively, pulses of approximately 200-fs, tunable over the range 1058-1076 nm, were obtained with either slit-tuning or a single-prism dispersive resonator. Output powers from 6 to 14 mW have been measured. PMID- 20588864 TI - A bistable polarizer-free electro-optical switch using a droplet manipulation on a liquid crystal and polymer composite film. AB - A bistable, polarizer-free, and reflective electro-optical switch based on a droplet manipulation on a liquid crystal and polymer composite film (LCPCF) is demonstrated. A color droplet on LCPCF can be manipulated by a wettability gradient owning to the distribution of LC directors anchored among the polymer grains on LCPCF. The contrast ratio is around 8:1 in a reflective mode. The potential applications of droplet manipulation are electronic papers and reflective displays. PMID- 20588865 TI - Nonlinear spectrum broadening of femtosecond laser pulses in photorefractive waveguide arrays. AB - In photorefractive waveguide arrays, the process and extent of spectral broadening of femtosecond laser pulse caused by self-phase modulation are studied theoretically and experimentally. The threshold of self-phase modulation is more than two times larger than the common threshold in a bulk sample, which affects the extent of spectral broadening dramatically. The coupling length and the ratio between the common threshold and the input peak intensity of the femtosecond laser pulse are the two key parameters dominating these phenomena. The experimental results confirm the theoretical expectation. PMID- 20588866 TI - Diabolical point and conical-like diffraction in periodic plasmonic nanostructures. AB - We present the formation of a singular (diabolical) point in k-space from a periodic metal-dielectric waveguide array. The singularity originates from the balance between alternating normal and anomalous coupling. We numerically demonstrate a strong diffraction anomaly (conical-like diffraction) near the singular point. We also show the evolution of the diffraction pattern with band deformation. The resultant peculiar propagation dynamics of surface plasmon polaritons could provide a new toolset for manipulating light on the nano-scale. PMID- 20588868 TI - Terahertz form birefringence. AB - We report on one-dimensional photonic crystals designed to exhibit a pronounced form birefringence at terahertz frequencies. The crystals can be used as volumetric quasioptical elements for a broad frequency range. Theoretical simulations of the dielectric parameters of these structures are presented as well as measurement results of a polymeric crystal that exhibit a birefringence of 0.25 at 300 GHz. As a potential application, the device is exemplarily used as terahertz wave plate. PMID- 20588867 TI - Numerical model based on successive order of scattering method for computing radiance distribution of underwater light fields. AB - A numerical model based on the successive order of scattering method has been developed. In this model, the vertical and angular distributions of underwater radiance are computed without using an empirical procedure, by assuming that a water body comprises numerous parallel horizontal layers. The model is validated using the observation data obtained from Lake Pend Oreille and Suruga Bay and for highly scattering water. The model results are in good agreement with the observation data. The model stability is demonstrated by assuming the single scattering albedo for highly scattering water to be 1.0. PMID- 20588869 TI - Experimental verification of soliton-like pulse-shaping mechanisms in passively mode-locked VECSELs. AB - We present a detailed experimental study on the influence of dispersion on the pulse formation in passively modelocked vertical-external-cavity surface-emitting lasers (VECSELs). We have demonstrated that the shortest pulse duration requires slightly positive dispersion to balance the nonlinear phase shift induced by strong semiconductor gain and absorber saturation. This is in contrast to soliton modelocking in ion-doped solid-state lasers - but similarities remain and will be discussed. Our results are in good qualitative agreement with numerical simulations and confirm the quasi-soliton modelocking mechanism of ultrafast VECSELs. PMID- 20588871 TI - Manipulating the field distribution via optical transformation. AB - Using the coordinate transformation theory, we propose a way to control the field distribution of electromagnetic wave in a waveguide filling with properly designed transformation media. The results show that the field distribution of the electromagnetic wave can be compressed and amplified in both longitudinal and transverse direction. A realizable layered waveguide based on the discrete optical transformation is also designed to manipulate the field distribution of the electromagnetic wave. Potential applications, i.e., turn a narrow (wide) slit into a large (small) window, are investigated in detail. PMID- 20588870 TI - Automatic deconvolution in 4Pi-microscopy with variable phase. AB - 4Pi-microscopy doubles the aperture of the imaging system by coherent addition of the wavefronts for illumination and/or detection through opposing objective lenses. This improves the axial resolution 3-7 fold, but the raw data usually features ghost images which have to be removed by image reconstruction. This straightforward procedure is sometimes precluded by imperfect alignment of the instrument or a specimen with strong variations of its refractive index, because the image formation process now depends on the space-variant phase difference between the counter-propagating wavefronts. Here we present a computationally fast method of parametric blind deconvolution that allows for automatic and robust simultaneous estimation of both the object and the phase function in such cases. We verify the performance of our approach on both synthetic and real data. Because the method does not require a-priori knowledge of the phase function it is major step towards reliable 4Pi-imaging and automatic image restoration by non expert users. PMID- 20588872 TI - A compact, continuous-wave terahertz source based on a quantum-cascade laser and a miniature cryocooler. AB - We report on the development of a compact, easy-to-use terahertz radiation source, which combines a quantum-cascade laser (QCL) operating at 3.1 THz with a compact, low-input-power Stirling cooler. The QCL, which is based on a two miniband design, has been developed for high output and low electrical pump power. The amount of generated heat complies with the nominal cooling capacity of the Stirling cooler of 7 W at 65 K with 240 W of electrical input power. Special care has been taken to achieve a good thermal coupling between the QCL and the cold finger of the cooler. The whole system weighs less than 15 kg including the cooler and power supplies. The maximum output power is 8 mW at 3.1 THz. With an appropriate optical beam shaping, the emission profile of the laser is fundamental Gaussian. The applicability of the system is demonstrated by imaging and molecular-spectroscopy experiments. PMID- 20588873 TI - Structuring materials with nanosecond laser pulses. AB - Ablation of silicon and metals is investigated using a 1064 nm pulsed fiber laser, with pulse energy up to 0.5 mJ, peak powers up to 10 kW, and pulse widths from 10 to 250 ns. A simple thermal model is employed to explain the dependence of scribe depth and shape on pulse energy or peak power. We demonstrate that pulses of high peak powers have shallow penetration depths, while longer pulses with lower peak powers have a higher material removal rate with deeper scribes. The key parameter that enables such variation of performance with changes in peak pulse power or peak irradiance on the material surface is the nonlinear increase of the absorption coefficient of silicon or metals as its temperature increases. PMID- 20588874 TI - Mueller matrix imaging of human colon tissue for cancer diagnostics: how Monte Carlo modeling can help in the interpretation of experimental data. AB - Colon samples with both healthy and cancerous regions have been imaged in diffuse light and backscattering geometry by using a Mueller imaging polarimeter. The tumoral parts at the early stage of cancer are found to be less depolarizing than the healthy ones. This trend clearly shows that polarimetric imaging may provide useful contrasts for optical biopsy. Moreover, both types of tissues are less depolarizing when the incident polarization is linear rather than circular. However, to really optimize an optical biopsy technique based on polarimetric imaging a realistic model is needed for polarized light scattering by tissues. Our approach to this goal is based on numerical Monte-Carlo simulations of polarized light propagation in biological tissues modeled as suspensions of monodisperse spherical scatterers representing the cell nuclei. The numerical simulations were validated by comparison with measurements on aqueous polystyrene sphere suspensions, which are commonly used as tissue phantoms. Such systems exhibit lower depolarization for incident linear polarization in the Rayleigh scattering regime, i.e. when the sphere diameters are smaller than the wavelength, which is obviously not the case for cell nuclei. In contrast, our results show that this behaviour can also be seen for "large" scatterers provided the optical index contrast between the spheres and the surrounding medium is small enough, as it is likely to be the case in biological tissues. PMID- 20588875 TI - Mechanisms of three-dimensional structuring of photo-polymers by tightly focussed femtosecond laser pulses. AB - Three-dimensional (3D) micro/nano-structuring of photo-resists is systematically studied at the close-to-dielectric- breakdown irradiance. It is demonstrated that avalanche absorption is playing a major part in free electron generation and chemical bond breaking at these conditions. The steps of photo-initiation and chemical bond breaking in propagation of polymerization are altered as compared with photo-polymerization at low-irradiance and one-photon stereo-lithography. The avalanche dominates radical generation and promotion of polymerization at tight focusing and a high approximately TW/cm(2) irradiance. The rates of electron generation by two-photon absorption and avalanche are calculated for the experimental conditions. Simulation results are corroborated by 3D polymerization in three resists with different photo-initiators at two different wavelengths and pulse durations. The smallest feature sizes of 3D polymerized logpile structures are consistent with spectral dependencies of the two photon nonlinearities. Implications of these findings for achieving sub-100 nm resolution in 3D structuring of photo-polymers are presented. PMID- 20588876 TI - Large phase-stepping approach for high-resolution hard X-ray grating-based multiple-information imaging. AB - High-resolution hard X-ray grating-based imaging method with conventional X-ray sources provides attenuation, refraction and scattering information synchronously, and it is regarded as the next-generation X-ray imaging technology for medical and industrial applications. In this letter, a large phase-stepping approach with at least one order of magnitude lower resolution of the movement is presented to equivalently substitute the current high-positioning-resolution phase-stepping approach. Both the theoretical deduction and actual experiment prove that the new approach is available to relax the requirement of high positioning resolution and strict circumstances so as to benefit the future commercial applications of the grating-based multiple-information imaging technology. PMID- 20588877 TI - Modification of ensemble emission rates and luminescence spectra for inhomogeneously broadened distributions of quantum dots coupled to optical microcavities. AB - We investigate the spontaneous emission modifications when ensembles of quantum dots (QDs) with differing emission frequencies and finite Lorentzian linewidths are coupled to a microcavity. Using contour integrals we develop a general expression for the rate enhancement when neither the emitter nor the cavity resonance can be treated as a delta function. We show that the ensemble cavity coupled luminescence lifetimes are generally suppressed in the case of spherical cavities and that the spontaneous emission dynamics of the cavity coupled component becomes increasingly stretched as the coupling factor increases. The Q factor measured from the luminescence spectrum can be much lower than the intrinsic cavity Q-factor, and is in many practical situations limited by the QD spectral width. The mode spectrum observed in the photoluminescence (PL) spectrum can be largely determined by the QD emission linewidth, permitting this parameter to be extracted without requiring single-particle spectroscopy. In the case of Si QDs, the linewidth cannot be significantly greater than 10 meV in order to observe spherical cavity resonances in the PL spectrum. PMID- 20588878 TI - Laser emission from mirrorless waveguides based on photosensitized polymers incorporating POSS. AB - Laser emission from leaky waveguides based in dye-doped organic gain media incorporating Polyhedral Oligomeric Silsesquioxanes (POSS) nanoparticles is reported. The samples consist of thin film gain media deposited onto glass substrate defining a planar asymmetric slab waveguide, which does not incorporate any resonant substructure. The presence of POSS results in additional amplified spontaneous emission (ASE) spectral narrowing, and conditions have been found for which directional multimode laser emission is achieved. The spectral narrowing is ascribed to the photon path enlargement caused by a non-resonant feedback mechanism provided by individual scatterers, which enhances incoherently the magnitude of the amplification process. On the contrary, the appearance of multimode lasing is attributed to coherent random lasing from a many scatterers collective effect. PMID- 20588879 TI - Real-time fluorescence lifetime imaging system with a 32 x 32 0.13microm CMOS low dark-count single-photon avalanche diode array. AB - A compact real-time fluorescence lifetime imaging microscopy (FLIM) system based on an array of low dark count 0.13microm CMOS single-photon avalanche diodes (SPADs) is demonstrated. Fast background-insensitive fluorescence lifetime determination is achieved by use of a recently proposed algorithm called 'Integration for Extraction Method' (IEM) [J. Opt. Soc. Am. A 25, 1190 (2008)]. Here, IEM is modified for a wider resolvability range and implemented on the FPGA of the new SPAD array imager. We experimentally demonstrate that the dynamic range and accuracy of calculated lifetimes of this new camera is suitable for widefield FLIM applications by imaging a variety of test samples, including various standard fluorophores covering a lifetime range from 1.6ns to 16ns, microfluidic mixing of fluorophore solutions, and living fungal spores of Neurospora Crassa. The calculated lifetimes are in a good agreement with literature values. Real-time fluorescence lifetime imaging is also achieved, by performing parallel 32 x 16 lifetime calculations, realizing a compact and low cost FLIM camera and promising for bigger detector arrays. PMID- 20588880 TI - Modified elliptically polarized light Z-scan method for studying third-order nonlinear susceptibility components. AB - The normal elliptically polarized light Z-scan method is modified by adding a quarter-wave plate and an analyzer before the detector. The normalized transmittance formulas of modified elliptically polarized light Z-scan are obtained for media with negligible nonlinear absorption. Compared with normal linearly and elliptically polarized light Z-scan methods, an increase of sensitivity by a factor of larger than 4 is achieved for the real part of third order susceptibility component's measurements using this modified elliptically polarized light Z-scan method. The analytical results are verified by studying the real part of independent susceptibility components of CS(2) liquid. Moreover, the potential application for cross-polarized wave generation is discussed. PMID- 20588881 TI - OTDM to WDM format conversion based on quadratic cascading in a periodically poled lithium niobate waveguide. AB - We propose and demonstrate error-free conversion of a 40 Gbit/s optical time division multiplexed signal to 4 x 10 Gbit/s wavelength division multiplexed channels based on cascaded second harmonic and difference frequency generation in a periodically poled lithium niobate waveguide. The technique relies on the generation of spectrally (and temporally) flat linearly chirped pulses which are then optically switched with short data pulses in the nonlinear waveguide. Error free operation was obtained for all channels with a power penalty below 2dB. PMID- 20588882 TI - Polarization independent two-way variable optical attenuator based on polymer stabilized cholesteric liquid crystal. AB - We have investigated the optical properties of the polymer-stabilized cholesteric liquid crystal (CLC). It was observed that the reflectance was decreased and the transmittance was increased with the increase of the applied voltage. Based on this property, a polarization independent two-way variable optical attenuator (VOA) has been demonstrated by sandwiching a lambda/2 film between two left handed polymer-stabilized CLC films. Different from a conventional VOA, the VOA based on our developed polymer-stabilized CLC can continuously change the optical intensity in both the reflection and transmission directions by applying voltage on it. This unique property will allow it to be widely used in many applications, such as optical communications. PMID- 20588883 TI - Modified resolution redistribution system for frameless hologram display module. AB - A frameless hologram display module employing a modified resolution redistribution system is proposed in this paper. The frameless display modules can be aligned two-dimensionally to realize a large display screen. The modified resolution redistribution system consists of a one-lens imaging system, a screen lens, and a multiple illumination system. The prototype module was constructed using a spatial light modulator with a resolution of 1,980 x 1,080, and a pixel pitch of 8.0 microm. The horizontal resolution was increased four times and the magnification of the imaging system was 2.88. The horizontal resolution was increased to 7,920 and the horizontal pixel pitch was reduced to 5.8 microm. The screen size of the module was 2.0 inches and the horizontal viewing angle was 6.3 degrees. PMID- 20588884 TI - Direct CATV modulation and phase remodulated radio-over-fiber transport system. AB - A novel transport system, with directly modulating community antenna television (CATV) signal downstream and phase-remodulating radio-over-fiber (ROF) signal upstream, is proposed and experimentally demonstrated. By modulating multi carriers CATV signal in amplitude domain and ROF signal in phase domain, a single optical wavelength is able to serve these two applications simultaneous. To be the first system of communicating CATV signal downstream and phase remodulating radio signal upstream, the performances of transmitting CATV and radio signals over 20 km single-mode fiber (SMF) were experimentally verified. Good performances of carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple beat (CTB) were obtained for CATV applications as well as high extinction ration (ER) and low bit error rate (BER) values were measured for ROF transmission. PMID- 20588885 TI - Narrow linewidth 578 nm light generation using frequency-doubling with a waveguide PPLN pumped by an optical injection-locked diode laser. AB - This study demonstrates 578 nm yellow light generation with a narrow linewidth using a waveguide periodically poled lithium niboate (PPLN) and an optical injection-locked diode laser. The frequency of an external cavity diode laser used as a master laser operating at 1156 nm in optical injection-locking mode was locked into a high-finesse cavity with the Pound-Drever-Hall technique, which results in a linewidth reduction of the master laser. The linewidth of the master laser was estimated to be approximately 1.6 kHz. In an effort to amplify the optical power, a distributed feed-back laser was phase-locked to the master laser by an optical injection-locking technique. A waveguide PPLN was used for second harmonic generation. Frequency-doubled yellow light of approximately 2.4 mW was obtained with a conversion efficiency of 6.5%. PMID- 20588886 TI - Dual-loss-modulated Q-switched and mode-locked YVO(4)/Nd:YVO(4)/KTP green laser with EO and Cr(4+):YAG saturable absorber. AB - By simultaneously employing the electro-optic (EO) modulator and Cr(4+):YAG saturable absorber, a diode-pumped dual-loss-modulated Q-switched and mode-locked (QML) YVO(4)/NdYVO(4)/KTP green laser is presented. In comparison with the singly passively QML green laser with Cr(4+):YAG, the dual-loss-modulated QML green laser with EO and Cr(4+):YAG can generate more stable pulse train with deeper modulation depth, shorter pulse width, greater pulse energy and higher peak power. For the dual-loss-modulated QML green laser, at a pump power of 18 W and a repetition rate of 1 kHz, the pulse width and the pulse energy of the Q-switch envelope as well as the peak power of QML green laser are 42.1 ns, 360 microJ and 382 kW, respectively, corresponding to the pulse width compression 62%, the pulse energy improvement 10 times and the QML peak power increase 40 times when compared with that of the singly passively QML green laser. PMID- 20588887 TI - Laser-self-mixing interferometry in the Gaussian beam approximation: experiments and theory. AB - We analyze the laser-self-mixing process in the Gaussian beam approximation and reformulate the expression of the feedback coefficient C in terms of the effective feedback power coupled back into the laser diode. Our model predicts a twenty-fold increase of the ratio between the maximum and the minimum measurable displacements judged against the current plane-wave model. By comparing the interaction of collimated or diverging Gaussian laser beams with a plane mirror target, we demonstrate that diverging beams tolerate larger wobbling during the target displacement and allow for measurement of off-axis target rotations up to the beam angular width. A novel method for reconstructing the phase front of the Gaussian beam by self-mixing scanning measurements is also presented. PMID- 20588888 TI - Distributed aperture synthesis. AB - Distributed aperture synthesis is an exciting technique for recovering high resolution images from an array of small telescopes. Such a system requires optical field values measured at individual apertures to be phased together so that a single, high-resolution image can be synthesized. This paper describes the application of sharpness metrics to the process of phasing multiple coherent imaging systems into a single high-resolution system. Furthermore, this paper will discuss hardware and present the results of simulations and experiments which will illustrate how aperture synthesis is performed. PMID- 20588889 TI - All-optical modulation-transparent wavelength multicasting in a highly nonlinear fiber Sagnac loop mirror. AB - An all-optical wavelength multicasting scheme using four-wave mixing (FWM) in a highly nonlinear fiber (HNLF) Sagnac loop mirror has been demonstrated. This proposed scheme has the advantage that even when the wavelength of a multicast channel overlaps with the pump-pump generated idler, clear eye diagram can still be observed. Six and ten 10-Gb/s multicast channels, compliant with the ITU grid, are successfully obtained by using two- and three-pump lasers, respectively. Multicasting of on-off shift keying (OOK) and differential phase-shift keying (DPSK) signals are both successfully demonstrated. The maximum power penalty of the multicast channels is less than 3.5 dB. Furthermore, compared with the non loop configuration, up to 1.2 dB power penalty improvement can be achieved in this proposed Sagnac loop configuration. PMID- 20588890 TI - Surface phonon polariton characteristics of In(0.04)Al(0.06)Ga(0.90)N/AlN/Al(2)O(3) heterostructure. AB - Surface phonon polariton (SPP) characteristics of In(0.04)Al(0.06)Ga(0.90)N/AlN/Al(2)O(3) heterostructure are investigated by means of p-polarized infrared (IR) attenuated total reflection spectroscopy. Two absorption dips corresponding to In(0.04)Al(0.06)Ga(0.90)N SPP modes are observed. In addition, two prominent dips and one relatively weak and broad dip corresponding to the Al(2)O(3) SPP mode, In(0.04)Al(0.06)Ga(0.90)N/Al(2)O(3) interface mode, and Al(2)O(3) bulk polariton mode, respectively, are clearly seen. No surface mode feature originating from the AlN layer is observed because it is too thin. Overall, the observations are in good agreement with the theoretical predictions. PMID- 20588891 TI - Coherent transport of nanowire surface plasmons coupled to quantum dots. AB - The coherent transport of surface plasmons with nonlinear dispersion relations on a metal nanowire coupled to two-level emitters is investigated theoretically. Real-space Hamiltonians are used to obtain the transmission and reflection spectra of the surface plasmons. For the single-dot case, we find that the scattering spectra can show completely different features due to the non-linear quadratic dispersion relation. For the double-dot case, we obtain the interference behavior in transmission and reflection spectra, similar to that in resonant tunneling through a double-barrier potential. Moreover, Fano-like line shape of the transmission spectrum is obtained due to the quadratic dispersion relation. All these peculiar behaviors indicate that the dot-nanowire system provides a onedimensional platform to demonstrate the bandgap feature widely observed in photonic crystals. PMID- 20588892 TI - Aspects for calculating local absorption with the rigorous coupled-wave method. AB - The calculation of local absorption is very important in the context of lithography and in photo-detector design. We present a rigorous method for calculating the local absorption in periodic structures. The computation depends primarily on the calculation of the electric field inside the structure. Since the standard definitions produce unsatisfactory results, we use a modified version of a method published by Lalanne [J. Modern Opt. 45, 1357 (1998)]. The results for these field definitions agree very accurately with results obtained by the law of conservation of energy. We present some examples which are typical for the application scenarios of lithography and detectors. PMID- 20588893 TI - Fractal plasmonic metamaterials for subwavelength imaging. AB - We show that a metallic plate with periodic fractal-shaped slits can be homogenized as a plasmonic metamaterial with plasmon frequency dictated by the fractal geometry. Owing to the all-dimensional subwavelength nature of the fractal pattern, our system supports both transverse-electric and transverse magnetic surface plasmons. As a result, this structure can be employed to focus light sources with all-dimensional subwavelength resolution and enhanced field strengths. Microwave experiments reveal that the best achievable resolution is only lambda/15, and finite-difference-time-domain simulations demonstrate that similar effects can be realized at infrared frequencies with appropriate designs. PMID- 20588894 TI - Charge and current reservoirs for electric and magnetic field enhancement. AB - Two optical antenna designs incorporating structures termed charge and current reservoirs are proposed to realize localized high electric and magnetic field enhancement, respectively. Simulation results show that the fan-rod electric antenna design combines the advantages of the rod antenna and the bowtie antenna, and has higher field enhancement than either. The performance of a loop shaped magnetic antenna consisting of a pair of metallic strips with offsets is also verified numerically, with high magnetic field enhancement being observed in the simulation. In both of the designs, the concepts of charge and current reservoirs contribute to high electric and magnetic field enhancement. PMID- 20588895 TI - Multiple ionization of oxygen studied by coincident measurement. AB - We experimentally study double and triple ionization of oxygen using a reaction microscope. The kinetic energy releases (KERs) and angular distributions are obtained through coincidentally measuring the ionic fragments of doubly or triply charged parent ions. The pathway O(2+)2 ? O (+) O(+)?proceeds through some excited electronic states. The KERs exhibit definite structures independent of the laser intensity and the pulse duration. However, the angular distribution of coincident O(+) reflects the symmetry of the highest occupied molecular orbital (HOMO) only for few-cycle laser pulses at low intensity. The pathways O(2+) 2 --> O(2+) +O and O(3+) 2 --> O(2+) + O(+) occur through some repulsive states. The KERs show a single broad peak and decrease with increasing the pulse duration. The decrease of KER comes from the stretch of the internuclear distance in intense laser fields. PMID- 20588896 TI - Image reconstruction exploiting object sparsity in boundary-enhanced X-ray phase contrast tomography. AB - Propagation-based X-ray phase-contrast tomography (PCT) seeks to reconstruct information regarding the complex-valued refractive index distribution of an object. In many applications, a boundary-enhanced image is sought that reveals the locations of discontinuities in the real-valued component of the refractive index distribution. We investigate two iterative algorithms for few-view image reconstruction in boundary-enhanced PCT that exploit the fact that a boundary enhanced PCT image, or its gradient, is often sparse. In order to exploit object sparseness, the reconstruction algorithms seek to minimize the l(1)-norm or TV norm of the image, subject to data consistency constraints. We demonstrate that the algorithms can reconstruct accurate boundary-enhanced images from highly incomplete few-view projection data. PMID- 20588897 TI - In situ detection and analysis of laser-induced damage on a 1.5-m multilayer dielectric grating compressor for high-energy, petawatt-class laser systems. AB - A grating-inspection system and a damage-analysis method have been developed to measure in situ laser-induced damage on a 1.5-m tiled-grating assembly of the OMEGA EP pulse compressor during a 15-ps, 2.2-kJ energy ramp. The beam fluence at which significant damage growth occurred was determined. This is the first report on beam fluence versus laser-induced-damage growth of meter-sized multilayer dielectric-diffraction gratings. This result was correlated to the damage probability measurement conducted on a small grating sample and is consistent with the fluence, corresponding to 100% damage probability. PMID- 20588898 TI - Impact of particulate oceanic composition on the radiance and polarization of underwater and backscattered light. AB - We use a Monte Carlo model to investigate how the particulate oceanic composition affects the radiance, the linear polarization, and the circular polarization of underwater and backscattered light. The Mueller matrices used in our simulations were computed using the T-matrix method. They are significantly different for organic and inorganic particles. Our Monte Carlo simulations show that these differences have a significant impact on the underwater and backscattered light, and that it may be possible to determine the ratio between the amounts of organic and inorganic particles from measurements of the full Stokes vector. PMID- 20588899 TI - Experimental validation of an optimized signal processing method to handle non linearity in swept-source optical coherence tomography. AB - We evaluate various signal processing methods to handle the non-linearity in wavenumber space exhibited by most laser sources for swept-source optical coherence tomography. The following methods are compared for the same set of experimental data: non-uniform discrete Fourier transforms with Vandermonde matrix or with Lomb periodogram, resampling with linear interpolation or spline interpolation prior to fast-Fourier transform (FFT), and resampling with convolution prior to FFT. By selecting an optimized Kaiser-Bessel window to perform the convolution, we show that convolution followed by FFT is the most efficient method. It allows small fractional oversampling factor between 1 and 2, thus a minimal computational time, while retaining an excellent image quality. PMID- 20588900 TI - Dynamic deformation of red blood cell in dual-trap optical tweezers. AB - Three-dimensional dynamic deformation of a red blood cell in a dual-trap optical tweezers is computed with the elastic membrane theory and is compared with the experimental results. When a soft particle is trapped by a laser beam, the particle is deformed depending on the radiation stress distribution whereas the stress distribution on the particle in turn depends on the deformation of its morphological shape. We compute the stress re-distribution on the deformed cell and its subsequent deformations recursively until a final equilibrium state solution is achieved. The experiment is done with the red blood cells in suspension swollen to spherical shape. The cell membrane elasticity coefficient is obtained by fitting the theoretical prediction with the experimental data. This approach allows us to evaluate up to 20% deformation of cell's shape. PMID- 20588901 TI - Hybrid fiber grating cavity for multi-parametric sensing. AB - We propose an all-fiber hybrid cavity involving two unbalanced uniform fiber Bragg gratings (FBGs) written at both sides of a tilted FBG (TFBG) to form an all fiber interferometer. This configuration provides a wavelength gated reflection signal with interference fringes depending on the cavity features modulated by spectral dips associated to the wavelength dependent optical losses due to cladding mode coupling occurring along the TFBG. Such a robust structure preserves the advantages of uniform FBGs in terms of interrogation methods and allows the possibility of simultaneous physical and chemical sensing. PMID- 20588902 TI - A quantitative theory and the generalized Bragg condition for surface plasmon Bragg reflectors. AB - We proposed a quantitative theory based on the surface plasmon polariton (SPP) coupled-mode model for SPP-Bragg reflectors composed of N periodic defects of any geometry and any refractive index profile. A SPP coupled-mode model and its recursive form were developed and shown to be equivalent. The SPP absorption loss, as well as high-order modes in each defect and possible radiation loss, is incorporated without effort. The simple recursive equations derived from the recursive model bridge the reflectance and the transmittance of N periodic defects to those of a single one, resulting in that the computational cost of the geometry optimization or the spectra calculation for N periodic defects is reduced into that for a single one. The model predictions show good agreement with fully vectorial computation data on the reflectance and the transmittance. From the recursive model, the generalized Bragg condition is proposed, which is verified by SPP-Bragg reflectors of various structures. The quantitative theory and the generalized Bragg condition proposed will greatly simplify the design of SPP-Bragg reflectors. PMID- 20588903 TI - Experimental demonstration of ultraviolet pulse broadening in short-range non line-of-sight communication channels. AB - An experimental test-bed using a narrow-pulsed ultraviolet (UV) laser and high bandwidth photomultiplier tube was set up to characterize pulse broadening effects in short-range non-line-of-sight (NLOS) scattering communication channels. Pulse broadening is reported as a function of the transmitter elevation angle, transmitter beam angle, receiver elevation angle, receiver field-of-view, and transmitter-receiver distance. The results provide insight into the channel bandwidth and achievable communication data rate. PMID- 20588904 TI - Lensless wide-field fluorescent imaging on a chip using compressive decoding of sparse objects. AB - We demonstrate the use of a compressive sampling algorithm for on-chip fluorescent imaging of sparse objects over an ultra-large field-of-view (>8 cm(2)) without the need for any lenses or mechanical scanning. In this lensfree imaging technique, fluorescent samples placed on a chip are excited through a prism interface, where the pump light is filtered out by total internal reflection after exciting the entire sample volume. The emitted fluorescent light from the specimen is collected through an on-chip fiber-optic faceplate and is delivered to a wide field-of-view opto-electronic sensor array for lensless recording of fluorescent spots corresponding to the samples. A compressive sampling based optimization algorithm is then used to rapidly reconstruct the sparse distribution of fluorescent sources to achieve approximately 10 microm spatial resolution over the entire active region of the sensor-array, i.e., over an imaging field-of-view of >8 cm(2). Such a wide-field lensless fluorescent imaging platform could especially be significant for high-throughput imaging cytometry, rare cell analysis, as well as for micro-array research. PMID- 20588905 TI - Lateral shift effect on the spatial interference of light wave propagating in the single-layered dielectric film. AB - Under the oblique incidence condition, the multiple reflection of wave packets in a layered film structure will have a lateral shift increasing with the film thickness. In the analysis of the spatial interference with consideration of the lateral shift effect, a set of new analytic formulae to normalize the intensity of the s-and p-polarized wave packet was obtained to reduce the error of the ellipsometry parameters significantly as the optical path difference delta is close to mpi. The principle and method developed in this work also can be applied to other film structures in more general applications. PMID- 20588906 TI - Measurement of the ratio of forward-propagating to back-propagating second harmonic signal using a single objective. AB - In this paper, we present a method to determine, for the first time, the ratio of forward-propagating second harmonic (SHG) signal to back-propagating SHG signal (F/B) in vivo on the surface of intact tissue samples without any biopsy or tissue sectioning, using only epidetection (i.e., via a single objective lens). This method has the additional benefit of using the confocal detection apparatus already contained within common commercially available two-photon laser-scanning microscopes, and hence can allow the measurement of the SHG F/B ratio in vivo with minimal purchase of new equipment. PMID- 20588907 TI - Reconstruction of optical fields with the Quasi-discrete Hankel transform. AB - Unlike the FFT, the Quasi Discrete Hankel Transform (QDHT) is not sampled on a uniform grid; in particular the field may no longer be sampled on axis. We demonstrate how the generalised sampling theorem may be applied to optical problems, evaluated with the QDHT, to efficiently and accurately reconstruct the optical field at any point. Without sacrificing numerical accuracy this is demonstrated to be typically 50x faster than using an equivalent 2D FFT. PMID- 20588908 TI - 100 nm period grating by high-index phase-mask immersion lithography. AB - The interferogram of a high index phase mask of 200 nm period under normal incidence of a collimated beam at 244 nm wavelength with substantially suppressed zeroth order produces a 100 nm period grating in a resist film under immersion. The paper describes the phase mask design, its fabrication, the effect of electron-beam lithographic stitching errors and optical assessment of the fabricated sub-cutoff grating. PMID- 20588909 TI - Wideband slow light in chirped slot photonic-crystal coupled waveguides. AB - Wideband dispersion-free slow light in chirped-slot photonic-crystal coupled waveguides is proposed and theoretically investigated in detail. By systematically analyzing the dependence of band shape on various structure parameters, unique inflection points in the key photonic band with approximate zero group velocity can be obtained in an optimized slot photonic-crystal coupled waveguide. By simply chirping the widths of the photonic-crystal waveguides in the optimized structure, wideband (up to 20 nm) slow-light with optical confinement in the low dielectric slot is demonstrated numerically with relative temporal pulse-width spreading well below 8% as obtained from two-dimensional finite-difference time-domain simulations. The wideband slow-light operation of the proposed structures would offer significant potential for novel compact high speed optical-signal-processing devices in silicon-based systems. PMID- 20588910 TI - The minimum Euclidean distance principle applied to improve the modulation diffraction efficiency in digitally controlled spatial light modulators. AB - Digital addressing of the electrical signal in spatial light modulators, as it is the case in present liquid crystal on silicon (LCoS) displays, may lead to temporal phase fluctuations in the optical beam. In diffractive optics applications a reduction in the modulation diffraction efficiency may be expected. Experimental work is done characterizing the fluctuations amplitude and phase depth for three different digital addressing sequences. We propose a diffractive model to evaluate the modulation diffraction efficiency of phase diffractive optical elements (DOEs) in the presence of phase fluctuations. Best results are obtained for the most stable electrical sequence even though its phase depth is as small as 280 degrees . The results show good agreement with the numerical calculation given by the model. PMID- 20588911 TI - High-speed optical transmissions over a second- and third-order dispersion managed DSF span with parametric tunable dispersion compensator. AB - A wideband and fast tunable chromatic dispersion compensator is one of the key components for the future high-speed optical transmissions. We have so far proposed and demonstrated a new tunable dispersion compensation scheme called parametric tunable dispersion compensator (P-TDC), which is based on the combination of parametric frequency conversion and frequency dependent dispersive media. The P-TDC has many attractive features such as a seamlessly wideband operation, wide tunable range and fast dispersion tuning. In fact, with appropriate configurations of dispersive media, the P-TDC can compensate the dispersion slope of transmission fibers even though the second-order dispersion is small. In this paper, we use such a P-TDC scheme and successfully achieve high speed optical transmissions over a second- and third-order dispersion managed dispersion shifted fiber (DSF) span. The transmission experiments show low penalty 172 Gbit/s return-to-zero on-off-keying transmissions over 126-km DSF. PMID- 20588912 TI - Electrically pumped 1.3 microm room-temperature InAs/GaAs quantum dot lasers on Si substrates by metal-mediated wafer bonding and layer transfer. AB - An electrically pumped InAs/GaAs quantum dot laser on a Si substrate has been demonstrated. The double-hetero laser structure was grown on a GaAs substrate by metal-organic chemical vapor deposition and layer-transferred onto a Si substrate by GaAs/Si wafer bonding mediated by a 380-nm-thick Au-Ge-Ni alloy layer. This broad-area Fabry-Perot laser exhibits InAs quantum dot ground state lasing at 1.31 microm at room temperature with a threshold current density of 600 A/cm(2). PMID- 20588913 TI - An integrated surface-plasmon source. AB - A compact and versatile source of coherent surface-plasmon polaritions (SPPs) is demonstrated by end-coupling a laser diode operating at 1.46 microm to a plasmonic waveguide integrated on the same microchip. With an optimized overlap between the spatial-modes of the laser and a planar-stripe waveguide, a high coupling efficiency of approximately 36% is achieved, that computations show could approach approximately 60% with smaller, readily achievable gaps between laser and waveguide. This integrated and electrically-activated source, with an available SPP power limited only by the laser diode, appears ideally suited for directly driving plasmonic circuitry or surface-enhanced sensors. PMID- 20588914 TI - Partially light-controlled imaging system based on High Temperature Poly-Silicon Thin Film Transistor-Liquid Crystal Display. AB - A partially light-controlled imaging system is proposed as a novel device. It is used to improve the imaging quality at the illumination of 1.979 x 10(5)lx by means of mitigating image contrast. It consists of a High Temperature Poly Silicon Thin Film Transistor-Liquid Crystal Display (HTPS TFT-LCD), which is set between the lens and CCD and is coupled with CCD by the optical fiber taper. The transmittance of pixelated LCD can be controlled by Field-Programmable Gate Array to realize the partially light-controlled and thus dynamic range of the imaging system can be extended. Samples of indoor objects and outdoor license plate are photographed by the prototype imaging system under strong light. The imaging results of this novel system are satisfactory with better restored details, compared with the photos taken by normal CCD camera (WAT-231S2) which uses aperture and shutter to control the overall light intensity. PMID- 20588915 TI - Single plane illumination fluorescence correlation spectroscopy (SPIM-FCS) probes inhomogeneous three-dimensional environments. AB - The life sciences require new highly sensitive imaging tools, which allow the quantitative measurement of molecular parameters within a physiological three dimensional (3D) environment. Therefore, we combined single plane illumination microscopy (SPIM) with camera based fluorescence correlation spectroscopy (FCS). SPIM-FCS provides contiguous particle number and diffusion coefficient images with a high spatial resolution in homo- and heterogeneous 3D specimens and live zebrafish embryos. Our SPIM-FCS recorded up to 4096 spectra within 56 seconds at a laser power of 60 microW without damaging the embryo. This new FCS modality provides more measurements per time and more, less photo-toxic measurements per sample than confocal based methods. In essence, SPIM-FCS offers new opportunities to observe biomolecular interactions quantitatively and functions in a highly multiplexed manner within a physiologically relevant 3D environment. PMID- 20588916 TI - Dynamics of material modifications following laser-breakdown in bulk fused silica. AB - We report on the material response during the cooling phase in bulk fused silica following localized energy deposition via laser-induced breakdown.We use a time resolved microscope system to acquire images of the region of energy deposition at delay times covering the entire timeline of events. In addition, this system is configured to perform pump-and-probe damage testing measurements to investigate the evolution of the transient absorption of the modified material. The main features of a damage site are established at approximately 30 ns after the pump pulse, i.e. cracks reach their final size within this time frame. The results reveal that the cracks and melted core exhibit a transient absorption up until about 300 ns and 200 micros delay times, respectively, and suggest that the melted region returns to solid phase at approximately 70 ms delay. PMID- 20588917 TI - Second-order statistics of stochastic electromagnetic beams propagating through non-Kolmogorov turbulence. AB - We present a detailed investigation, qualitative and quantitative, on how the atmospheric turbulence with a non-Kolmogorov power spectrum affects the major statistics of stochastic electromagnetic beams, such as the spectral composition and the states of coherence and polarization. We suggest a detailed survey on how these properties evolve on propagation of beams generated by electromagnetic Gaussian Schell-model sources, depending on the fractal constant alpha of the atmospheric power spectrum. PMID- 20588918 TI - Automatic image segmentation for concealed object detection using the expectation maximization algorithm. AB - We address an image segmentation method to detect concealed objects captured by passive millimeter wave (MMW) imaging. Passive MMW imaging can create interpretable imagery on the objects concealed under clothing, which gives the great advantage to the security system. In this paper, we propose the multi-level expectation maximization (EM) method to separate the concealed objects from the other area in the image. We apply the EM method to obtain a Gaussian mixture model (GMM) of the acquired image. In the experiments, we evaluate the performance by the average probability of error. We will show that the consecutive EM processes separates the object area more accurately than the conventional EM method. PMID- 20588919 TI - Electrically pumped wavelength-tunable ultraviolet random lasing from Mg(x)Zn(1 x)O films on Si. AB - We report the electrically pumped wavelength-tunable ultraviolet random lasing from Mg(x)Zn(1-x)O films with different bandgap energies, which act as the semiconductor components in metal-insulator- semiconductor (MIS) structures fabricated on Si substrates. When the metal (Au herein) gates of the MIS structures are applied with sufficiently high positive voltages, random lasing from the Mg(x)Zn(1-x)O films occurs, featuring a series of narrow spikes in the emitted spectra. Overall, the central wavelength of the random lasing spectrum is tuned from approximately 377 to 352 nm with the increase of x value in Mg(x)Zn(1 x)O from 0 to 0.35. The mechanism for the electrically pumped random lasing has been tentatively elucidated taking into account both the multiple optical scattering and the optical gain proceeding in the Mg(x)Zn(1-x)O films. PMID- 20588920 TI - MQWs InGaN/GaN LED with embedded micro-mirror array in the epitaxial-lateral overgrowth gallium nitride for light extraction enhancement. AB - Multi-quantum wells (MQWs) InGaN/GaN LEDs, 300 microm x 300 microm chip size, were fabricated with Ta(2)O(5) / SiO(2) dielectric multi-layer micro-mirror array (MMA) embedded in the epitaxiallateral- overgrowth (ELOG) gallium nitride (GaN) on the c-plane sapphire substrate. MQWs InGaN/GaN LEDs with ELOG embedded patterned SiO(2) array (P-SiO(2)) of the same dimension as the MMA were also fabricated for comparison. Dislocation density was reduced for the ELOG samples. 75.2% light extraction enhancement for P-SiO(2)-LED and 102.6% light extraction enhancement for MMA-LED were obtained over the standard LED. We showed that multiple-diffraction with high intensity from the MMA redirected the trap lights to escape from the LED causing the light extraction enhancement. PMID- 20588921 TI - Analysis of surface-plasmon-polaritons-assisted interference imaging by using silver film with rough surface. AB - In the surface plasmon polaritons (SPPs) interference lithography, the scattering effect caused by the rough surface of silver film deteriorates the quality of lithography patterns. Research shows that under this condition the light field in the photoresist is not the results of SPPs interference but comes from the SPPs assisted imaging in which the scattered light propagates from the upper surface of the silver film to the photoresist. The near-field optical transfer function (NOTF) is used to study this process and a method of evaluating the imaging quality is presented. The validity of NOTF is verified by both SPPs assisted interference imaging experiments and simulations by the FDTD. It is also shown that the NOTF method is not only a convenient approach to describe the nano-scale information transmission in the near-field but also a good method to optimize experimental parameters. PMID- 20588922 TI - Validation of a crop field modeling to simulate agronomic images. AB - In precision agriculture, crop/weed discrimination is often based on image analysis but though several algorithms using spatial information have been proposed, not any has been tested on relevant databases. A simple model that simulates virtual fields is developed to evaluate these algorithms. Virtual fields are made of crops, arranged according to agricultural practices and represented by simple patterns, and weeds that are spatially distributed using a statistical approach. It ensures a user-defined Weed Infestation Rate (WIR). Then, experimental devices using cameras are simulated with a pinhole model. Its ability to characterize the spatial reality is demonstrated through different pairs (real, virtual) of pictures. Two spatial descriptors (nearest neighbor method and Besag's function) have been set up and tested to validate the spatial realism of the crop field model, comparing a real image to the homologous virtual one. PMID- 20588923 TI - Fringe image analysis based on the amplitude modulation method. AB - A novel phase-analysis method is proposed. To get the fringe order of a fringe image, the amplitude-modulation fringe pattern is carried out, which is combined with the phase-shift method. The primary phase value is obtained by a phase-shift algorithm, and the fringe-order information is encoded in the amplitude modulation fringe pattern. Different from other methods, the amplitude-modulation fringe identifies the fringe order by the amplitude of the fringe pattern. In an amplitude-modulation fringe pattern, each fringe has its own amplitude; thus, the order information is integrated in one fringe pattern, and the absolute fringe phase can be calculated correctly and quickly with the amplitude-modulation fringe image. The detailed algorithm is given, and the error analysis of this method is also discussed. Experimental results are presented by a full-field shape measurement system where the data has been processed using the proposed algorithm. PMID- 20588924 TI - Highly efficient nonradiative energy transfer mediated light harvesting in water using aqueous CdTe quantum dot antennas. AB - We present light harvesting of aqueous colloidal quantum dots to nonradiatively transfer their excitonic excitation energy efficiently to dye molecules in water, without requiring ligand exchange. These as-synthesized CdTe quantum dots that are used as donors to serve as light-harvesting antennas are carefully optimized to match the electronic structure of Rhodamine B molecules used as acceptors for light harvesting in aqueous medium. By varying the acceptor to donor concentration ratio, we measure the light harvesting factor, along with substantial lifetime modifications of these water-soluble quantum dots, from 25.3 ns to 7.2 ns as a result of their energy transfer with efficiency levels up to 86%. Such nonradiative energy transfer mediated light harvesting in aqueous medium holds great promise for future quantum dot multiplexed dye biodetection systems. PMID- 20588925 TI - Two-fold symmetric geometries for tailored phase-matching in birefringent solid core air-silica microstructured fibers. AB - The effect of birefringence in 2-fold-symmetric microstructured optical fibers on the phase matching conditions for four-wave mixing is analyzed. The three general types of four-wave mixing are considered. General features are obtained through analytic expansions of phase-matching formulas. Three commonly used designs of fibers are analyzed numerically. Particular designs allow the generation of specified wavelengths, supercontinuum or entangled photons. PMID- 20588926 TI - Cavity length resonances in a nanosecond singly resonant optical parametric oscillator. AB - Resonant output energy enhancement in a singly resonant nondegenerate type-I optical parametric oscillator with a volume Bragg grating output coupler is demonstrated. The resonances occur when the pump laser and parametric oscillator cavity length ratio is an integer or a fraction of small integers. Although the length resonances are similar to those observed in doubly resonant optical parametric oscillators, the physical mechanism is distinctly different. The resonances in the singly resonant oscillator are caused by correlation of the instantaneous power between the quasi-periodic multimode pump laser beam and the OPO signal. PMID- 20588927 TI - Room temperature photon number resolving detector for infared wavelengths. AB - In this paper we present a photon number resolving detector at infrared wavelengths, operating at room temperature and with a large dynamic range. It is based on the up-conversion of a signal at 1559 nm into visible wavelength and on its detection by a thermoelectrically cooled multi-pixel silicon avalanche photodiodode, also known as a Silicon Photon Multiplier. With the appropriate up conversion this scheme can be implemented for arbitrary wavelengths above the visible spectral window. The preservation of the poissonian statistics when detecting coherent states is studied and the cross-talk effects on the detected signal can be easily estimated in order to calibrate the detector. This system is well suited for measuring very low intensities at infrared wavelengths and for analyzing multiphoton quantum states. PMID- 20588929 TI - Non-contact, automated cardiac pulse measurements using video imaging and blind source separation. AB - Remote measurements of the cardiac pulse can provide comfortable physiological assessment without electrodes. However, attempts so far are non-automated, susceptible to motion artifacts and typically expensive. In this paper, we introduce a new methodology that overcomes these problems. This novel approach can be applied to color video recordings of the human face and is based on automatic face tracking along with blind source separation of the color channels into independent components. Using Bland-Altman and correlation analysis, we compared the cardiac pulse rate extracted from videos recorded by a basic webcam to an FDA-approved finger blood volume pulse (BVP) sensor and achieved high accuracy and correlation even in the presence of movement artifacts. Furthermore, we applied this technique to perform heart rate measurements from three participants simultaneously. This is the first demonstration of a low-cost accurate video-based method for contact-free heart rate measurements that is automated, motion-tolerant and capable of performing concomitant measurements on more than one person at a time. PMID- 20588930 TI - Introduction: unconventional polarization States of light focus issue. PMID- 20588931 TI - Full Poincare beams. AB - We explore the behavior of a class of fully correlated optical beams that span the entire surface of the Poincare sphere. The beams can be constructed from a coaxial superposition of a fundamental Gaussian mode and a spiral-phase Laguerre Gauss mode having orthogonal polarizations. When the orthogonal polarizations are right and left circular, the coverage extends from one pole of the sphere to the other in such a way that concentric circles on the beam map onto parallels on the Poincare sphere and radial lines map onto meridians. If the beam waist parameters match, the map is stereographic and the beam propagation corresponds to a rigid rotation about the pole. We present an experimental example of how a symmetrically stressed window can produce these beams and show that the predicted rotation indeed occurs when moving through the beams' focus. PMID- 20588932 TI - A new type of vector fields with hybrid states of polarization. AB - We present an idea based on Poincare sphere and demonstrate the creation of a new type of vector fields, which have hybrid states of polarization. Such a type of hybridly polarized vector fields have completely different property from the reported scalar and vector fields. The novel vector fields are anticipated to result in new effects, phenomena, and applications. PMID- 20588933 TI - The Pancharatnam-Berry phase for non-cyclic polarization changes. AB - We present a novel setup that allows the observation of the geometric phase that accompanies polarization changes in monochromatic light beams for which the initial and final states are different (so-called non-cyclic changes). This Pancharatnam-Berry phase can depend in a linear or in a nonlinear fashion on the orientation of the optical elements, and sometimes the dependence is singular. Experimental results that confirm these three types of behavior are presented. The observed singular behavior may be applied in the design of optical switches. PMID- 20588934 TI - Real-time measurement of unique space-variant polarizations. AB - A configuration for real-time measurement of unique, space-variant, polarizations is presented. The experimental results reveal that the full state of polarization at each location within the beam can be accurately obtained every 10 msec, limited only by the camera frame rate. We also present a more compact configuration which can be modified to determine the real-time wavelength variant polarization measurements. PMID- 20588935 TI - Polarization characterization in the focal volume of high numerical aperture objectives. AB - In this paper the polarization states of linearly and radially polarized plane wave and doughnut beams in the focal volume of high numerical aperture objectives are studied. Through manipulating the incident polarization states of laser beams as well as the apodization of an objective and adjusting the numerical aperture of an objective, focal fields dominantly with either one transverse component or one longitudinal component can be generated. Furthermore, tailored polarization distributions with three polarization components of the same strength are also found. PMID- 20588936 TI - Focusing of a femtosecond vortex light pulse through a high numerical aperture objective. AB - We investigate the focusing properties of a femtosecond vortex light pulse focused by a high numerical aperture objective. By using the Richards-Wolf vectorial diffraction method, the intensity distribution, the velocity variation and the orbital angular momentum near the focus are studied in great detail. We have discovered that the femtosecond vortex light pulse can travel at various speeds, that is, slower or faster than light with a tight focusing system. Moreover, we have found that the numerical aperture of the focusing objective and the duration of the vortex light pulse will influence the orbital angular momentum distribution in the focused field. PMID- 20588937 TI - Optical trapping of micrometer-sized dielectric particles by cylindrical vector beams. AB - Single-beam optical trapping of micrometer-sized dielectric particles is experimentally demonstrated using radially and azimuthally polarized beams. The axial and transverse optical trapping efficiencies of glass and polystyrene beads suspended in water are measured. The radially polarized beam exhibited the highest trapping efficiency in the axial direction due to the p polarization of the radial polarization on the particle surface. On the other hand, the azimuthally polarized beam had a higher transverse trapping efficiency than the radially polarized beam. These results are consistent with numerical predictions. PMID- 20588938 TI - An all-fiber laser generating cylindrical vector beam. AB - We proposed and demonstrated an all-fiber laser to generate cylindrical vector beam. A pair of fiber-based collimators was used to select the cylindrical vector beam operating. The radially and azimuthally polarized modes can be switchable just by applying pressure to a section of fiber in our fiber laser system. A 70 cm long Yb-doped fiber was used as gain medium and the lasing wavelength was around 1030 nm. PMID- 20588939 TI - Vectorial fiber laser using intracavity axial birefringence. AB - In this paper we investigate the polarization properties of a fiber laser with an intracavity c-cut calcite crystal that is capable of producing reconfigurable vectorial output modes. Vectorial modes with radial, azimuthal and generalized cylindrical vector polarizations can be generated by translating one lens within the laser cavity. Detailed studies of the mode polarization evolution show that the modes inside the laser cavity can be spatially homogeneously polarized in one section of the cavity while being spatially inhomogeneously polarized in another section of the cavity, which opens the opportunities for many potential new fiber laser design possibilities and applications. Furthermore, more complicated vectorial vortex output modes are also observed by purposefully introducing angular misalignments. PMID- 20588940 TI - Spatially engineered polarization states and optical vortices in uniaxial crystals. AB - We describe how the propagation of light through uniaxial crystals can be used as a versatile tool towards the spatial engineering of polarization and phase, thereby providing an all-optical technique for vectorial and scalar singular beam shaping in optics. Besides the prominent role played by the linear birefringence, the influence of circular birefringence (the optical activity) is discussed as well and both the monochromatic and polychromatic singular beam shaping strategies are addressed. Under cylindrically symmetric light-matter interaction, the radially, azimuthally, and spirally polarized eigen-modes for the light field are revealed to be of a fundamental interest to describe the physical mechanisms at work when dealing with scalar and vectorial optical singularities. In addition, we also report on nontrivial effects arising from cylindrical symmetry breaking, e.g. tilting the incident beam with respect to the crystal optical axis. PMID- 20588941 TI - Structured light for focusing surface plasmon polaritons. AB - We propose a structureless method for focusing surface plasmon polaritons (SPPs) on a flat metal film under illumination of radially polarized cogwheel-like structured light beams. Without metal structures, the locally induced SPPs can further be propagated following the predefined patterns to form symmetric focal spots with dimensions beyond diffraction limit. Benefiting from the radial polarization, this method can be employed to pattern various center-symmetric evanescent distributions for generating SPPs reconfigurably. The SPPs will be propagating and focusing in radial directions. PMID- 20588942 TI - Demonstration of an elliptical plasmonic lens illuminated with radially-like polarized field. AB - We demonstrate an elliptically symmetric plasmonic lens that is illuminated by a radially-like polarization field. This illumination function is TM polarized with regard to the plasmonic lens, ensuring optimum coupling of the incident light into surface plasmons polaritons. The structure is analyzed theoretically by using the Green function approach, and a finite difference time domain simulation. Both approaches provide similar results. Specifically we calculate and experimentally measure the field distribution on the surface and a few microns above it. The results show strong dependency of the electric field distribution on the eccentricity of the elliptic structure and the illumination wavelength. The interference of surface plasmons generates a structured pattern consisting of distinct peaks distributed inside the ellipse with locations that are wavelength dependent. This pattern can be used in several applications including structured illumination microscopy, particles beam trapping and sensing. PMID- 20588943 TI - Nanofocusing radially-polarized beams for high-throughput funneling of optical energy to the near field. AB - We theoretically show that a weakly-focused radially polarized beam can excite surface-plasmon-polaritons in metal nanowires and nanocones with efficiencies of the order of 90% and large bandwidths. The coupling mechanism relies on the formation of a standing wave on the nanowire facet, which imposes a relationship between the operating wavelength and the nanowire radius. An immediate application of this finding is nanofocusing of optical energy for implementations of ultra-fast and high-throughput linear and nonlinear nanoscopies, optical nanolithographies, quantum nano-optics and photochemistry at the nanoscale. PMID- 20588944 TI - Effects of scatterers' sizes on near-field coherent anti-Stokes Raman scattering under tightly focused radially and linearly polarized light excitation. AB - We employ the finite-difference time-domain (FDTD) technique as a numerical approach to studying the effects of scatterers' sizes on near-field coherent anti Stokes Raman scattering (CARS) microscopy under tightly focused radially and linearly polarized light excitations. The FDTD results show that in a uniform medium (water), the full width at half maximum (FWHM) (transverse resolution) of radially polarized near-field CARS (RP-CARS) radiation is approximately 7.7% narrower than that of linearly polarized near-field CARS (LP-CARS) imaging, whereas the depth of focus (DOF) of RP-CARS radiation is 6.5% longer than LP CARS. However, with the presence of scatterers in the uniform medium, both the FHWM and DOF of near-field RP-CARS radiation become much narrower compared to those of near-field LP-CARS radiation. In addition, the signal to nonresonant background ratio of near-field RP-CARS is significantly improved when the scatterer's size is larger than a half wavelength of the pump light field. This work suggests that near-field CARS radiations are strongly influenced by the scatterers' sizes in the medium; and near-field RP-CARS microscopy is superior to the near-field LP-CARS by providing both higher transverse and axial resolutions for three-dimensional molecular imaging of fine structures in biological systems. PMID- 20588945 TI - Extraordinary transmission through a single coaxial aperture in a thin metal film. AB - We investigate experimentally the transmission properties of single sub wavelength coaxial apertures in thin metal films (t = 110 nm). Enhanced transmission through a single sub-wavelength coaxial aperture illuminated with a strongly focused radially polarized light beam is reported. In our experiments we achieved up to four times enhanced transmission through a single coaxial aperture as compared to a (hollow) circular aperture with the same outer diameter.We attribute this enhancement of transmission to the excitation of a TEM-mode for illumination with radially polarized light inside the single coaxial aperture. A strong polarization contrast is observed between the transmission for radially and azimuthally polarized illumination. Furthermore, the observed transmission through a single coaxial aperture can be strongly reduced if surface plasmons are excited. The experimental results are in good agreement with finite difference time domain (FDTD) simulations. PMID- 20588946 TI - On the experimental investigation of the electric and magnetic response of a single nano-structure. AB - We demonstrate an experimental method to separately test the optical response of a single sub-wavelength nano-structure to tailored electric and magnetic field distributions in the optical domain. For this purpose a highly focused y polarized TEM10-mode is used which exhibits spatially separated longitudinal magnetic and transverse electric field patterns. By displacing a single sub wavelength nano-structure, namely a single split-ring resonator (SRR), in the focal plane, different coupling scenarios can be achieved. It is shown experimentally that the single split-ring resonator tested here responds dominantly as an electric dipole. A much smaller but yet statistically significant magnetic dipole contribution is also measured by investigating the interaction of a single SRR with a magnetic field component perpendicular to the SRR plane (which is equivalent to the curl of the electric field) as well as by analyzing the intensity and polarization distribution of the scattered light with high spatial resolution. The developed experimental setup as well as the measurement techniques presented in this paper are a versatile tool to investigate the optical properties of single sub-wavelength nano-structures. PMID- 20588947 TI - Pulsed pumping of silicon nanocrystal light emitting devices. AB - Typical silicon nanocrystal light emitting devices (LEDs) operate under direct current (DC) biasing conditions that require high electric fields or high current densities. The electroluminescence (EL) under these conditions relies on impact excitation that can be damaging to the material. In this work, we present bipolar injection into silicon nanocrystal LEDs using a pulsed pumping scheme. We measured the frequency dependence of the integrated and time-resolved EL of the LEDs. The frequency dependent behavior of the time-resolved characteristics is used to explain the integrated EL measurements. In addition, the light output of the device was measured under pulsed excitation and was found to increase by a factor of 18 as compared to the case of DC excitation. PMID- 20588948 TI - Monochromatic aberrations in resonant optical elements applied to a focusing multilevel reflectarray. AB - The monochromatic aberrations produced by the phase distribution reflected by resonant sub-wavelength metallic structures are studied both analytically and numerically. Even for normal incidence, the angular dependence of the re-radiated wavefront disturbs the overall performance of the reflectarray. This effect is modelled as combination of a linear and a cubic dependence. A complete numerical simulation of a multilevel focusing reflectarray is performed using computational electromagnetic and physical-optics-propagation methods. A modified Strehl ratio is defined to show the dependence of the focused spot behavior on aperture. The irradiance distribution is dependent on the polarization state. A small-aperture focusing reflectarray has been designed, fabricated, and tested. The irradiance distribution at the focusing plane is compared with the simulated one, showing a good agreement when residual wavefront aberrations are included. PMID- 20588949 TI - Wavelength-tunable silicon microring modulator. AB - We present a wavelength-tunable, compact, high speed and low power silicon microring modulator. With a ring radius of 5 microm, we demonstrate a modulator with a high speed of 12.5 Gbps and a driving voltage of 3 V to achieve approximately 6 dB extinction ratio in high speed measurement. More importantly, tunability of the resonant wavelength is accomplished by means of a microheater on top of the ring, with an efficiency of 2.4 mW/nm (2.4 mW is needed to tune the resonant wavelength by 1 nm). This device aims to solve the narrow bandwidth problem of silicon microcavity modulators and increase the data bandwidth in optical interconnect systems. PMID- 20588950 TI - Light induced patterning of poly(dimethylsiloxane) microstructures. AB - A new method for direct patterning of Poly(dimethylsiloxane) (PDMS) microstructures is developed by taking advantage of photorefractive effect in a functionalized substrate. Here we show that when a x-cut Iron doped Lithium Niobate (LN) crystal is exposed to appropriate structured laser light, a charge density pattern builds-up in the crystal and a space charge field arise that is able to induce self-patterning of the PDMS liquid film deposited on its surface via the dielectrophoretic effects. Proper heating treatment allows to achieve polymeric linking process creating a solid and stable PDMS microstructures. The self-patterned structures replicate the illuminating light pattern. We show that 1D and 2D patterning of PDMS gratings can be achieved. This new soft-lithographic approach can pave the way for realizing PDMS micro-structures with high degree of flexibility that avoids the need of moulds fabrication. PMID- 20588951 TI - Defect solitons in two-dimensional optical lattices. AB - We report on the existence and stability of solitons in a defect embedded in a square optical lattice based on a photorefractive crystal with focusing saturable nonlinearity. These solitons exist in different bandgaps due to the change of defect intensity. For a positive defect, the solitons only exist in the semi infinite gap and can be stable in the low power region but not the high power region. For a negative defect, the solitons can exist not only in the semi infinite gap, but also in the first gap. With increasing the defect depth, these solitons are stable within a moderate power region in the first gap while unstable in the entire semi-infinite gap. PMID- 20588952 TI - Modulated vortex solitons of four-wave mixing. AB - We experimentally demonstrate the vortex solitons of four-wave mixing (FWM) in multi-level atomic media created by the interference patterns with superposing three or more waves. The modulation effect of the vortex solitons is induced by the cross-Kerr nonlinear dispersion due to atomic coherence in the multi-level atomic system. These FWM vortex patterns are explained via the three-, four- and five-wave interference topologies. PMID- 20588953 TI - Analysis of liquid-to-solid coupling and other performance parameters for microfluidically reconfigurable photonic systems. AB - In this paper, we analytically investigate the coupling of light from liquid-core waveguides to conventional solid-core waveguides and a series of other optical properties of liquid waveguides in order to gauge the practicality of such a system for use in microfluidically reconfigurable photonic systems. A finite element model of the system was constructed and relevant properties such as mode field diameter, attenuation, bending loss, and efficiency of evanescent and end fire coupling were investigated as a function of the liquid waveguide Peclet number and the relative difference in refractive index. For pure liquid systems we show that the mode field diameter decreases monotonically with increasing Peclet number and that bending losses could be significantly reduced by increasing the Peclet number. More critically, we observed irreversible evanescent coupling, in which the light coupled in the solid waveguide is entrapped within the solid rather than coupled back into the liquid waveguide. This effect was caused by the lengthwise variation in the propagation constant of the liquid core due to downstream diffusion. We demonstrate that coupling efficiencies as high as 84% can be obtained for fluid based end-fire coupling by taking advantage of the tunable mode field diameter. By developing techniques for coupling light between liquid and solid states we hope to be able to overcome the drawbacks of solid waveguide systems (e.g. unchangeable structure and properties) and liquid waveguide systems (e.g. diversion and attenuation) yielding a new paradigm for reconfigurable photonics. PMID- 20588954 TI - Cavity-enhanced generation of 6 W cw second-harmonic power at 532 nm in periodically-poled MgO:LiTaO3. AB - We report on efficient cw high-power second harmonic generation in a periodically poled LiTaO3 crystal placed in a resonant enhancement cavity. We tested three configurations, differing in the coupling mirror reflectivity, and a maximum conversion efficiency of about 76%, corresponding to 6.1 W of green light with 8.0 W of fundamental power, was achieved. This is, to the best of our knowledge, the highest cw power ever reported using a periodically-poled crystal in an external cavity. We observed photo-thermal effect induced by photon absorption at the mirrors and in the crystal, which however does not affect stable operation of the cavity. A further effect arises for two out of the three configurations, at higher values of the input power, which degrades the performance of the locked cavity. We suggest this effect is due to the onset of competing nonlinearities in the same crystal. PMID- 20588955 TI - Hybrid gap modes induced by fiber taper waveguides: application in spectroscopy of single solid-state emitters deposited on thin films. AB - We show, via simulations, that an optical fiber taper waveguide can be an efficient tool for photoluminescence and resonant, extinction spectroscopy of single emitters, such as molecules or colloidal quantum dots, deposited on the surface of a thin dielectric membrane. Placed over a high refractive index membrane, a tapered fiber waveguide induces the formation of hybrid mode waves, akin to dielectric slotted waveguide modes, that provide strong field confinement in the low index gap region. The availability of such gap-confined waves yields potentially high spontaneous emission enhancement factors (approximately 20), fluorescence collection efficiencies (approximately 23%), and transmission extinction (approximately 20%) levels. A factor of two improvement in fluorescence and extinction levels is predicted if the membrane is instead replaced with a suspended channel waveguide. Two configurations, for operation in the visible (approximately 600 nm) and near-infrared (approximately 1300 nm) spectral ranges are evaluated, presenting similar performances. PMID- 20588956 TI - Passive mode-locked lasing by injecting a carbon nanotube-solution in the core of an optical fiber. AB - In this paper, we propose a saturable absorber (SA) device consisting on an in fiber micro-slot inscribed by femtosecond laser micro fabrication, filled by a dispersion of Carbon Nanotubes (CNT). Due to the flexibility of the fabrication method, efficient and simple integration of the mode-locking device directly into the optical fiber is achieved. Furthermore, the fabrication process offers a high level of control over the dimensions and location of the micro-slots. We apply this fabrication flexibility to extend the interaction length between the CNT and the propagating optical field along the optical fiber, hence enhancing the nonlinearity of the device. Furthermore, the method allows the fabrication of devices that operate by either a direct field interaction (when the central peak of the propagating optical mode passes through the nonlinear media) or an evanescent field interaction (only a fraction of the optical mode interacts with the CNT). In this paper, several devices with different interaction lengths and interaction regimes are investigated. Self-starting passively modelocked laser operation with an enhanced nonlinear interaction is observed using CNT-based SAs in both interaction regimes. This method constitutes a simple and suitable approach to integrate the CNT into the optical system as well as enhancing the optical nonlinearity of CNT-based photonic devices. PMID- 20588957 TI - Effects of chirp on two-dimensional Fourier transform electronic spectra. AB - We examine the effect that pulse chirp has on the shape of two- dimensional electronic spectra through calculations and experiments. For the calculations we use a model two electronic level system with a solvent interaction represented by a simple Gaussian correlation function and compare the resulting spectra to experiments carried out on an organic dye molecule (Rhodamine 800). Both calculations and experiments show that distortions due to chirp are most significant when the pulses used in the experiment have different amounts of chirp, introducing peak shape asymmetry that could be interpreted as spectrally dependent relaxation. When all pulses have similar chirp the distortions are reduced but still affect the anti-diagonal symmetry of the peak shapes and introduce negative features that could be interpreted as excited state absorption. PMID- 20588958 TI - High-efficiency vertical GaN slab light-emitting diodes using self-coherent directional emitters. AB - We demonstrate a highly-efficient, large-area (1x1 mm2) GaN slab light-emitting diode using a vertically directional emitter produced from constructive interference. The vertical radiation can be coupled effectively into leaky modes from the beginning and thus a high-extraction efficiency can be expected with reduced material absorption. The far-field measurements show that the desired vertical emission profiles are obtained by varying the thickness of the dielectric layer between the emitter and bottom silver mirror. With the combination of a light extractor of a randomly textured surface, the output power was increased approximately 1.4 fold compared to a non-patterned device at a standard current of 350 mA without electrical degradation. PMID- 20588959 TI - Pump scheme for gain-flattened Raman fiber amplifiers using improved particle swarm optimization and modified shooting algorithm. AB - An effective pump scheme for the design of broadband and flat gain spectrum Raman fiber amplifiers is proposed. This novel approach uses a new shooting algorithm based on a modified Newton-Raphson method and a contraction factor to solve the two point boundary problems of Raman coupled equations more stably and efficiently. In combination with an improved particle swarm optimization method, which improves the efficiency and convergence rate by introducing a new parameter called velocity acceptability probability, this scheme optimizes the wavelengths and power levels for the pumps quickly and accurately. Several broadband Raman fiber amplifiers in C+L band with optimized pump parameters are designed. An amplifier of 4 pumps is designed to deliver an average on-off gain of 13.3 dB for a bandwidth of 80 nm, with about +/-0.5 dB in band maximum gain ripples. PMID- 20588960 TI - Flat supercontinuum generation in cascaded fibers pumped by a continuous wave laser. AB - We realize the flattening and extending of a CW-pumped supercontinuum with a high spectral intensity peak at the pump region. It is achieved by cascading a long zero-dispersion wavelength high-nonlinearity fiber with the output photonic crystal fiber, in order to improve the conversion efficiency of residual pump energy to long-wavelength continuum based on the effect of cascaded stimulated Raman scattering. Compared with the non-flattened continuum of 10.3 W with 3 dB bandwidth of 62 nm and 10 dB bandwidth of 360 nm, a flat continuum of 8 W with 3 dB spectral range of 340 nm and 10 dB spectral range of 420 nm is obtained. The spectral peak at the pump region decreases more than 5 dB, below the level of long-wavelength spectral intensity. Also, the long-wavelength edge has been extended by 60 nm. PMID- 20588961 TI - Actively Q-switched all-fiber laser with an electrically controlled microstructured fiber. AB - Actively Q-switching of an all-fiber laser system is demonstrated. The active element is a polarization switch with nanosecond risetime based on a microstructured fiber with electrically driven internal electrodes. Optical feedback between two 100% reflectors is inhibited until a nanosecond current pulse Q-switches the laser. After a short optical pulse develops several roundtrips later, the fiber switch is turned off, removing the short optical pulse from the cavity through a polarization splitter. Pulses of 50 W peak power and approximately 12 ns duration are obtained with 400 mW pump power at 100 Hz. PMID- 20588962 TI - Watt-level self-frequency-doubling Nd:GdCOB lasers. AB - Laser-diode (LD) pumped self-frequency doubling (SFD) Nd:GdCa4O(BO3)3 (Nd:GdCOB) miniature laser was demonstrated. The output power as high as 1.35 W was achieved which is over than five times than previous values for Nd:LnCa4O(BO3)3 (Ln=Y or Gd) SFD lasers and becomes the highest continuous-wave output power in this field to our knowledge. The maximum optical conversion efficiency is 17%. By comparison, we found that the cutting direction along its optimal phase-matching direction out of the principal planes is the determining factor resulting in this watt-level efficient output power. Different with previous studies, the emission wavelength is centered at about 545 nm. We believed that this efficient laser will become the most competitive one in the existing commercial green lasers, especially in the laser display, medical treatment and spectroscopic analysis etc. PMID- 20588963 TI - Full down-conversion of amber-emitting phosphor-converted light-emitting diodes with powder phosphors and a long-wave pass filter. AB - This paper reports the possibility of a facile optical structure to realize a highly efficient monochromatic amber-emitting light-emitting diode (LED) using a powder-based phosphor-converted LED combined with a long-wave pass filter (LWPF). The capping of a blue-reflecting and amber-passing LWPF enhances both the amber emission from the silicate amber phosphor layer and the color purity due to the blocking and recycling of the pumping blue light from the InGaN LED. The enhancement of the luminous efficacy of the amber pc-LED with a LWPF (phosphor concentration 20 wt%, 39.4 lm/W) is 34% over that of an amber pc-LED without a LWPF (phosphor concentration 55 wt%, 29.4 lm/W) at 100 mA and a high color purity (>96%) with Commission International d'Eclairage (CIE) color coordinates of x=0.57 and y=0.42. PMID- 20588964 TI - Automated suppression of sample-related artifacts in Fluorescence Correlation Spectroscopy. AB - Fluorescence Correlation Spectroscopy (FCS) in cells often suffers from artifacts caused by bright aggregates or vesicles, depletion of fluorophores or bleaching of a fluorescent background. The common practice of manually discarding distorted curves is time consuming and subjective. Here we demonstrate the feasibility of automated FCS data analysis with efficient rejection of corrupted parts of the signal. As test systems we use a solution of fluorescent molecules, contaminated with bright fluorescent beads, as well as cells expressing a fluorescent protein (ICA512-EGFP), which partitions into bright secretory granules. This approach improves the accuracy of FCS measurements in biological samples, extends its applicability to especially challenging systems and greatly simplifies and accelerates the data analysis. PMID- 20588965 TI - Basic diffraction phenomena in time domain. AB - Using a recently developed technique (SEA TADPOLE) for easily measuring the complete spatiotemporal electric field of light pulses with micrometer spatial and femtosecond temporal resolution, we directly demonstrate the formation of theo-called boundary diffraction wave and Arago's spot after an aperture, as well as the superluminal propagation of the spot. Our spatiotemporally resolved measurements beautifully confirm the time-domain treatment of diffraction. Also they prove very useful for modern physical optics, especially in micro- and meso optics, and also significantly aid in the understanding of diffraction phenomena in general. PMID- 20588966 TI - Low-loss surface-plasmonic nanobeam cavities. AB - One-dimensional surface-plasmonic nanobeam cavities are proposed as a means to confine surface plasmons to a subwavelength-scale mode volume, while maintaining a relatively high Q-factor. By bonding one-dimensional photonic-crystal nanobeam structures to a low-loss metallic substrate, a clear plasmonic TM bandgap can be formed. The introduction of a single-cell defect alongside the engineering of side-air-hole shifts to this plasmonic-crystal nanobeam provides subwavelength scale plasmonic mode localization within the plasmonic TM bandgap. This suppresses radiation and scattering loss to render a maximum Q-factor of 413 and a modal volume of 3.67x10(-3) microm3 at room temperature. The possibility of further reduction in the intrinsic loss of the cavity is investigated by lowering the operating temperature and the Q-factor of 1.34x10(4) is predicted at a temperature of 20 K for the optimistic case. PMID- 20588967 TI - Thin autofocus camera module by a large-stroke micromachined deformable mirror. AB - The conventional auto-focus and zoom image systems were made by a set of motor moved lenses. Because of mechanical moving parts, it is not easy to miniaturize their sizes. In this paper, we propose a thin autofocus system using a large stroke MEMS (micro-electro-mechanical systems) deformable mirror which has the potential to downscale the size and to minimize chromatic aberration. The large stroke MEMS deformable mirror is made by a polyimide membrane that has a maximum 12 microm displacement over a 3 mm aperture. The module size is 5.4 mm thick in optical design layout and 6.7 mm after packaging. This autofocus system is designed with the f-number=4.13, on-axis MTF=0.28 at full frequency of 230 cycles/mm, and incident light within+/-26 degree. The position of clear image can vary from 4 cm to 50 cm achieved by controlling the surface curvature of the MEMS deformable mirror. PMID- 20588968 TI - Traveling-wave Uni-Traveling Carrier photodiodes for continuous wave THz generation. AB - The design, experimental evaluation and performance of a Traveling-Wave Uni Traveling Carrier photodiode for Terahertz generation are described and its advantages in terms of frequency response are demonstrated. The device delivered 148 microW at 457 GHz, 24 microW at 914 GHz when integrated with resonant antennas and 105 microW at 255 GHz, 30 microW at 408 GHz, 16 microW at 510 GHz and 10 microW at 612 GHz. Record levels of Terahertz figure of merit (PTHz/Popt2 in W(-1)) were achieved ranging from 1 W(-1) at 110 GHz to 0.0024 W(-1) at 914 GHz. PMID- 20588969 TI - A wavelength demultiplexing structure based on metal-dielectric-metal plasmonic nano-capillary resonators. AB - A structure based on plasmonic nano-capillary resonators for optical wavelengths demultiplexing is proposed and numerically investigated. The structure consists of main/bus waveguide connected with series of nano-capillary resonators, each of which tuned at different wavelength transmission band. A model based on resonator theory is given to design the working wavelength of the structure. Both analytical and simulation results reveal that the demultiplexing wavelength of each channel has linear and nonlinear relationships with length and width of the nano-capillary structure. PMID- 20588970 TI - Seven-core multicore fiber transmissions for passive optical network. AB - We design and fabricate a novel multicore fiber (MCF), with seven cores arranged in a hexagonal array. The fiber properties of MCF including low crosstalk, attenuation and splice loss are described. A new tapered MCF connector (TMC), showing ultra-low crosstalk and losses, is also designed and fabricated for coupling the individual signals in-and-out of the MCF. We further propose a novel network configuration using parallel transmissions with the MCF and TMC for passive optical network (PON). To the best of our knowledge, we demonstrate the first bi-directional parallel transmissions of 1310 nm and 1490 nm signals over 11.3-km of seven-core MCF with 64-way splitter for PON. PMID- 20588971 TI - One-Watt level mid-IR output, singly resonant, continuous-wave optical parametric oscillator pumped by a monolithic diode laser. AB - We report more than 1.1 Watt of idler power at 3373 nm in a singly resonant optical parametric oscillator (SRO), directly pumped by a single-frequency monolithic tapered diode laser. The SRO is based on a periodically poled MgO:LiNbO3 crystal in a four mirror cavity and is excited by 8.05 W of 1062 nm radiation. The SRO pump power at threshold is 4 W. The internal slope-efficiency and conversion efficiency reach 89% and 44% respectively. The signal and idler waves are temperature tuned in the range of 1541 to 1600 nm and 3154 to 3415 nm respectively. To the best of our knowledge, this is the highest output obtained for a diode pumped optical parametric oscillator (OPO), and the first time a SRO is directly pumped by a monolithic tapered diode laser. PMID- 20588972 TI - Slow light in the GaAs-rod-loaded metallic waveguide for terahertz wave. AB - The modes in a circular metallic waveguide loaded with a high permittivity dielectric rod may possess similar dispersion relations to the modes in the left handed metamaterial (LHM) waveguide. Therefore such dielectric-loaded metallic waveguide may also support slow light with parameters properly selected. The slow light in the GaAs-rod-loaded metallic waveguide is numerically studied. The results show that the wavelength of slow light varies with the parameters of the waveguide. A linearly tapered waveguide and other realizable simple structures are proposed accordingly to realize the "trapped rainbow" phenomena. Moreover, the practical lossy tapered waveguide is also investigated in the terahertz region. It is shown that the slow light with low loss can be achieved in a realistic GaAs-loaded metallic waveguide. PMID- 20588973 TI - Technique of fiber optics used to localize epidural space in piglets. AB - Technique of loss-of-resistance in epidural block is commonly used for epidural anesthesia in humans with approximately 90% successful rate. However, it may be one of the most difficult procedures to learn for anesthesia residents in hospital. A two-wavelength (650 nm and 532 nm) fiber-optical method has been developed according to the characteristic reflectance spectra of ex-vivo porcine tissues, which are associated with the needle insertion to localize the epidural space (ES). In an in-vivo study in piglets showed that the reflected lights from ES and its surrounding tissue ligamentum flavum (LF) are highly distinguishable. This indicates that this technique has potential to localize the ES on the spot without the help of additional guiding assistance. PMID- 20588974 TI - Fluorescence lifetime endoscopy using TCSPC for the measurement of FRET in live cells. AB - Development of remote imaging for diagnostic purposes has progressed dramatically since endoscopy began in the 1960's. The recent advent of a clinically licensed intensity-based fluorescence micro-endoscopic instrument has offered the prospect of real-time cellular resolution imaging. However, interrogating protein-protein interactions deep inside living tissue requires precise fluorescence lifetime measurements to derive the Forster resonance energy transfer between two tagged fluorescent markers. We developed a new instrument combining remote fiber endoscopic cellular-resolution imaging with TCSPC-FLIM technology to interrogate and discriminate mixed fluorochrome labeled beads and expressible GFP/TagRFP tags within live cells. Endoscopic-FLIM (e-FLIM) data was validated by comparison with data acquired via conventional FLIM and e-FLIM was found to be accurate for both bright bead and dim live cell samples. The fiber based micro-endoscope allowed remote imaging of 4 microm and 10 microm beads within a thick Matrigel matrix with confident fluorophore discrimination using lifetime information. More importantly, this new technique enabled us to reliably measure protein-protein interactions in live cells embedded in a 3D matrix, as demonstrated by the dimerization of the fluorescent protein-tagged membrane receptor CXCR4. This cell based application successfully demonstrated the suitability and great potential of this new technique for in vivo pre-clinical biomedical and possibly human clinical applications. PMID- 20588975 TI - Tuning spectral properties of ultrafast laser ablation plasmas from brass using adaptive temporal pulse shaping. AB - Using automated laser pulse temporal shaping we report on enhancing spectral emission characteristics of ablation plasmas produced by laser irradiation of brass on ultrafast time scales. For different input irradiance levels, control of both atomic and ionic species becomes possible concerning the yield and the excitation state. The improved energy coupling determined by tailored pulses induces material ejection with lower mechanical load that translates into hot gas phase regions with higher excitation degrees and reduced particulates. PMID- 20588976 TI - Nonlinear spectroscopic properties of Yb3+-doped sesquioxides Lu2O3 and Sc2O3. AB - We report on the measurements of near-UV excited-state absorption (ESA) spectra and refractive index changes (RICs) in the two ytterbium doped laser crystals Yb:Lu2O3 and Yb:Sc2O3. ESA is assigned to ligand-to-metal charge transfer (LMCT) absorption transitions and RICs to the polarizability changes experienced by the Yb3+ ions due to these strong electric-dipole allowed absorption bands. PMID- 20588977 TI - Lensfree on-chip microscopy over a wide field-of-view using pixel super resolution. AB - We demonstrate lensfree holographic microscopy on a chip to achieve approximately 0.6 microm spatial resolution corresponding to a numerical aperture of approximately 0.5 over a large field-of-view of approximately 24 mm2. By using partially coherent illumination from a large aperture (approximately 50 microm), we acquire lower resolution lensfree in-line holograms of the objects with unit fringe magnification. For each lensfree hologram, the pixel size at the sensor chip limits the spatial resolution of the reconstructed image. To circumvent this limitation, we implement a sub-pixel shifting based super-resolution algorithm to effectively recover much higher resolution digital holograms of the objects, permitting sub-micron spatial resolution to be achieved across the entire sensor chip active area, which is also equivalent to the imaging field-of-view (24 mm2) due to unit magnification. We demonstrate the success of this pixel super resolution approach by imaging patterned transparent substrates, blood smear samples, as well as Caenoharbditis Elegans. PMID- 20588978 TI - Compact silicon photonic waveguide modulator based on the vanadium dioxide metal insulator phase transition. AB - We have integrated lithographically patterned VO2 thin films grown by pulsed laser deposition with silicon-on-insulator photonic waveguides to demonstrate a compact in-line absorption modulator for use in photonic circuits. Using single mode waveguides at lambda=1550 nm, we show optical modulation of the guided transverse-electric mode of more than 6.5 dB with 2 dB insertion loss over a 2 microm active device length. Loss is determined for devices fabricated on waveguide ring resonators by measuring the resonator spectral response, and a sharp decrease in resonator quality factor is observed above 70 degrees C, consistent with switching of VO2 to its metallic phase. A computational study of device geometry is also presented, and we show that it is possible to more than double the modulation depth with modified device structures. PMID- 20588979 TI - Impact of titanium adhesion layers on the response of arrays of metallic split ring resonators (SRRs). AB - At higher frequencies (visible and infrared) both the dimensions and the individual metal properties play an important role in determining the resonant response of arrays of SRRs. As a result, a substantial difference between the responses of gold- and Al-based SRR arrays has been observed. Additionally, deposition of gold SRRs onto a substrate typically involves the use of an additional adhesion layer. Titanium (Ti) is the most common adhesive thin-film material used to attach gold onto dielectric/semiconductor substrates. In this paper we investigate the impact of the Ti adhesion layer on the overall response of Au-based nano-scale SRRs. The results quantify the extent to which the overall difference in the resonance frequencies between Au- and Al-based SRRs is due to the presence of the Ti. We show that even a 2-nm-thick Ti layer can red-shift the position of SRR resonance by 20 nm. Finally, we demonstrate that by intentional addition of titanium in the Au-based SRRs, their overall resonant response can be tuned widely in frequency, but at the expense of resonance magnitude. PMID- 20588980 TI - A silicon nitride microdisk resonator with a40-nm-thin horizontal air slot. AB - We design and fabricate pedestal-type, 15 microm diameter silicon nitride microdisk resonators on Si chip with horizontal air-slot using selective wet etching between Si, SiO2, and SiNx. As the slot structure is determined by deposition process, air slots that are as thin as 40 nm and as deep as 5 microm with ultra-smooth slot surfaces can easily be fabricated with photolithography only. Fundamental TM-like slot mode in which the E-field is greatly enhanced within slot was observed with an intrinsic Q factor of approximately 34,000 (lambdares=1523.7 nm) and energy overlap in slot region of 21.6%. PMID- 20588981 TI - Dielectric metamaterial magnifier creating a virtual color image with far-field subwavelength information. AB - We propose an approach for far-field optical subwavelength imaging by using a dielectric metamaterial magnifier with gradient refractive index. Different from previous superlens and hyperlens that form a real image with subwavelength features within narrowband, this magnifier creates a virtual color image with sub 100 nm resolution over broadband that can be captured directly by a conventional microscope in the far field. Because the magnifier is made of isotropic dielectric materials, the fabrication will be greatly simplified with existing metamaterial technologies. PMID- 20588982 TI - 131 fs, 33 MHz all-fiber soliton laser at 1.07 microm with a film-type SWNT saturable absorber coated on polyimide. AB - We present a 1.07 microm all-fiber femtosecond soliton laser employing a film type saturable absorber with a P3HT (poly-3-hexylthiophene) incorporated SWNT coated on polyimide film. We optimized the laser cavity as a dispersion-managed soliton laser with photonic crystal fiber (PCF) as an anomalous dispersion fiber at 1.07 microm. As a result, a 131 fs, 33 MHz pulse was successfully generated with a simple laser configuration. PMID- 20588983 TI - Modulation response of nanoLEDs and nanolasers exploiting Purcell enhanced spontaneous emission. AB - The modulation bandwidth of quantum well nanoLED and nanolaser devices is calculated from the laser rate equations using a detailed model for the Purcell enhanced spontaneous emission. It is found that the Purcell enhancement saturates when the cavity quality-factor is increased, which limits the maximum achievable spontaneous recombination rate. The modulation bandwidth is thereby limited to a few tens of GHz for realistic devices. PMID- 20588984 TI - High yield fabrication of low threshold single-mode GaAs/AlGaAs semiconductor ring lasers using metallic etch masks. AB - We demonstrate a novel high yield fabrication process for single-mode ridge waveguide GaAs/AlGaAs ring lasers with significantly lower threshold currents than previously reported for similar devices. In this fabrication process, the ridge waveguide structure is patterned using a metallic etch mask, which survives ensuing fabrication steps to form a continuous metallic cover over the entire resonator structure. This metallic cover improves the uniformity of electrical contact between the resonator structure and the metallic biasing layer deposited at the conclusion of the fabrication process. This leads to optimum electrical pumping of the fabricated devices. This fabrication process also allows for the passivation of the ridge-waveguide device sidewalls and separation of the metallic biasing layer from the optical mode. PMID- 20588985 TI - Minimizing intensity fluctuations in dynamic holographic optical tweezers by restricted phase change. AB - We present a method for reducing intensity fluctuations that typically occur when a spatial light modulator is updated between consecutive computer generated holograms. The method is applicable to most iterative hologram generating algorithms and minimizes the average phase difference between consecutive holograms. Applications with high stability requirements, such as optical force measurement with holographic optical tweezers, should benefit from this improvement. PMID- 20588986 TI - Free spectral range measurement of a fiberized Fabry-Perot etalon with sub-Hz accuracy. AB - In this work a narrow linewidth (1 kHz) laser source is used to measure the free spectral range of a fiberized Fabry-Perot etalon with sub-Hz accuracy (10(-8)). A previously demonstrated technique based on the Pound-Drever-Hall error signal is improved in accuracy by the use of a narrow linewidth laser swept in frequency via an acousto-optic modulator, or single sideband generation. The sub-Hz (10( 8)) accuracy attained enables the characterization of both the long-term drift and the polarization dependence of the free spectral range of the fiberized etalon. PMID- 20588987 TI - Design and simulation of multimode interference based demultiplexers aided by computer-generated planar holograms. AB - A 1.31/1.55 microm multimode interference based wavelength demultiplexer aided by computer-generated planar holograms is proposed. The device length is not limited to the common multiples of the beat lengths for the two wavelengths. The demultiplexer length is chosen as the first self-imaging length for 1.55 microm input, and a computer-generated holographic pattern is used to image the 1.31 microm input to the cross output port. The design and optimization of the holographic pattern is presented. The device performance is investigated using the beam propagation method. PMID- 20588988 TI - Virtual conversion from metal object to dielectric object using metamaterials. AB - We propose an illusion device which transforms a perfectly-electric-conducting (PEC) object into a virtual dielectric object with arbitrary material parameters. Such an illusion device has unconventional electromagnetic properties as verified by accurate numerical simulations. The presented illusion device is composed of inhomogeneous and anisotropic media with finite and positive permittivity and permeability components. Hence the designed device is possible to be realized using artificial metamaterials. PMID- 20588989 TI - Influence of carrier lifetime on performance of silicon p-i-n variable optical attenuators fabricated on submicrometer rib waveguides. AB - We investigated influence of carrier lifetime on performance of silicon (Si) p-i n variable optical attenuators (VOAs) on submicrometer Si rib waveguides. VOAs were fabricated with and without intentional implantation of lattice defects into their intrinsic region. Carrier lifetime was measured by pulse responses for normal incidence of picosecond laser pulse of 775 nm to the VOA, as approximately 1 ns and approximately 7 ns for the VOAs with and without defects, respectively. Carrier lifetime is determined by the sum of surface recombination and Auger recombination for VOAs without defects, while Schockley-Read-Hall recombination is dominant for the VOA with defects. As a result, attenuation efficiency (dB/mA) is 0.2-0.7 and 0.04-0.1, while 3-dB bandwidth is 40-100 MHz and over 200 MHz for the VOAs with and without defects, respectively. There is a trade-off relation between attenuation and response speed of the VOAs with respect to carrier lifetime i.e., attenuation efficiency is linearly proportional to the carrier lifetime, whereas response speed is inversely proportional to it. PMID- 20588990 TI - Optimization of bull's eye structures for transmission enhancement. AB - We present an exhaustive exploration of the parameter space defining the optical properties of a bull's eye structure, both experimentally and theoretically. By studying the resonance intensity variations associated with the different geometrical features, several parameters are seen to be interlinked and scale laws emerge. From the results it is possible to give a simple recipe to design a bull's eye structure with optimal transmission properties. PMID- 20588991 TI - Analysis and identification of phase error in phase measuring profilometry. AB - Both the analysis of phase errors which occur at the abrupt discontinuities in phase measuring profilometry (PMP) and the identification method are presented in this paper. The sampling effect of CCD will cause a dilution of accuracy in PMP, especially at abrupt discontinuities on the object surface. The existing methods cannot efficiently identify the abrupt discontinuities. We analyze the relationship between the phase, the height and the equivalent wavelength. By viewing the phase as the argument of a vector we find out that CCD sampling introduces errors into the measurement and the phase is nonlinear to the equivalent wavelength at the abrupt discontinuities. Therefore temporal phase unwrapping (TPU) is introduced into the measurement to identify the abrupt discontinuities. Computer simulations and practical experiment validate the feasibility of this method. PMID- 20588992 TI - Mid-infrared modulated polarization gating for ultra-broadband supercontinuum generation. AB - We propose a method to control the harmonic process by a mid-IR modulated polarization gating for the effective generation of an ultra-broadband supercontinuum in the neutral rare-gas media. Using a mid-IR polarization gating pulse modulated by a weaker 800-nm linearly polarized pulse, the ionization, acceleration and recombination steps in the harmonic process are simultaneously controlled, leading to the efficient generation of an ultra-broadband supercontinuum covered by the spectral range from ultraviolet to water window x ray under the low ionization rate. The right phase-matching technique is employed to macroscopically select the short quantum path of the supercontinuum, then isolated sub-100-as pulses with tunable wavelengths are directly obtained. This supercontinuum also supports the pulse duration far below one atomic unit of time. PMID- 20588993 TI - Coherent electro-optical detection of terahertz radiation from an optical parametric oscillator. AB - We report the realization of coherent electro-optical detection of nanosecond terahertz (THz) pulses from an optical parametric oscillator, which is pumped by a Q-switched nanosecond Nd:YVO4 laser at 1064 nm and emits at approximately 1.5 THz. The beam profile and wavefront of the THz beam at focus are electro optically characterized toward the realization of a real-time THz camera. A peak dynamic range of approximately 37 dB/radical Hz is achieved with single-pixel detection. PMID- 20588994 TI - Reduction of image blurring of horizontally scanning holographic display. AB - A horizontally scanning holographic display offers a wide viewing angle and a large hologram size. To obtain this display, a series of images generated by a high-speed spatial light modulator are imaged to vertically long images (elementary holograms) by an anamorphic imaging system and are aligned horizontally by a horizontal scanner. However, scan error and focusing error cause blurring in the reconstructed images. In this study, the scan error is corrected by measuring the positions and pixel pitches of the elementary holograms in advance. The focusing error is corrected by experimentally determining the focusing parameter that is used to calculate the elementary holograms. PMID- 20588995 TI - Enhancing fluorescence of quantum dots by silica-coated gold nanorods under one- and two-photon excitation. AB - Nano-composites of quantum dots (QDs) and gold nanorods (GNRs) or silica-coated GNRs (GNRs_SiO2) were synthesized. The attached GNRs modify the excitation intensity and spontaneous emission of QDs through the surface plasmonic effects. The fluorescence from QDs is enhanced and can be optimized by modifying the thickness of silica coated on GNRs, under both one- and two-photon excitations. The measurements of fluorescence intensity and lifetime demonstrate that the enhancement may be attributed to the matching of the localized surface plasmon resonance of GNR to the excitation wavelength. In addition to enhancing QD fluorescence in QD-GNR@SiO2, GNRs also present as an effective contrast agent for bio-imaging, through light scattering and or two-photon emission, as well as for photo-thermal therapy. The composite's multifunctional characteristics are highly valuable and to be exploited in bio-applications. PMID- 20588997 TI - Performance evaluation of coherent WDM PS-QPSK (HEXA) accounting for non-linear fiber propagation effects. AB - Coherent-detection (CoD) permits to fully exploit the four-dimensional (4D) signal space consisting of the in-phase and quadrature components of the two fiber polarizations. A well-known and successful format exploiting such 4D space is Polarization-multiplexed QPSK (PM-QPSK). Recently, new signal constellations specifically designed and optimized in 4D space have been proposed, among which polarization-switched QPSK (PS-QPSK), consisting of a 8-point constellation at the vertices of a 4D polychoron called hexadecachoron. We call it HEXA because of its geometrical features and to avoid acronym mix-up with PM-QPSK, as well as with other similar acronyms. In this paper we investigate the performance of HEXA in direct comparison with PM-QPSK, addressing non-linear propagation over realistic links made up of 20 spans of either standard single mode fiber (SSMF) or non-zero dispersion-shifted fiber (NZDSF). We show that HEXA not only confirms its theoretical sensitivity advantage over PM-QPSK in back-to-back, but also shows a greater resilience to non-linear effects, allowing for substantially increased span loss margins. As a consequence, HEXA appears as an interesting option for dual-format transceivers capable to switch on-the-fly between PM-QPSK and HEXA when channel propagation degrades. It also appears as a possible direct competitor of PM-QPSK, especially over NZDSF fiber and uncompensated links. PMID- 20588998 TI - Near-infrared fluorescence catheter system for two-dimensional intravascular imaging in vivo. AB - Detection of high-risk coronary arterial plaques prior to rupture remains an unmet clinical challenge, in part due to the stringent resolution and sensitivity requirements for in vivo human coronary arterial imaging. To address this need, we have developed a near-infrared (NIR) fluorescence imaging catheter system for intra-vascular molecular imaging of atherosclerosis in coronary artery-sized vessels, capable of resolving two-dimensional fluorescence activity in hollow organs, such as blood vessels. Based on a rotational fiber design, the catheter system illuminates and detects perpendicular to the rotational axis, while an automated pullback mechanism enables visualization along blood vessels with a scan speed of up to 1.5 mm/sec. We demonstrate the previously undocumented capacity to produce intravascular NIR fluorescence images of hollow organs in vivo and showcase the performance metrics of the system developed using blood vessel mimicking phantoms. This imaging approach is geared toward in vivo molecular imaging of atherosclerotic biomarkers and is engineered to allow seamless integration into the cardiac catheterization laboratory. PMID- 20588996 TI - Automated volumetric evaluation of stereoscopic disc photography. AB - PURPOSE: To develop a fully automated algorithm (AP) to perform a volumetric measure of the optic disc using conventional stereoscopic optic nerve head (ONH) photographs, and to compare algorithm-produced parameters with manual photogrammetry (MP), scanning laser ophthalmoscope (SLO) and optical coherence tomography (OCT) measurements. METHODS: One hundred twenty-two stereoscopic optic disc photographs (61 subjects) were analyzed. Disc area, rim area, cup area, cup/disc area ratio, vertical cup/disc ratio, rim volume and cup volume were automatically computed by the algorithm. Latent variable measurement error models were used to assess measurement reproducibility for the four techniques. RESULTS: AP had better reproducibility for disc area and cup volume and worse reproducibility for cup/disc area ratio and vertical cup/disc ratio, when the measurements were compared to the MP, SLO and OCT methods. CONCLUSION: AP provides a useful technique for an objective quantitative assessment of 3D ONH structures. PMID- 20588999 TI - Optimal algorithm for fluorescence suppression of modulated Raman spectroscopy. AB - Raman spectroscopy permits probing of the molecular and chemical properties of the analyzed sample. However, its applicability has been seriously limited to specific applications by the presence of a strong fluorescence background. In our recent paper [Anal. Chem. 82, 738 (2010)], we reported a new modulation method for separating Raman scattering from fluorescence. By continuously changing the excitation wavelength, we demonstrated that it is possible to continuously shift the Raman peaks while the fluorescence background remains essentially constant. In this way, our method allows separation of the modulated Raman peaks from the static fluorescence background with important advantages when compared to previous work using only two [Appl. Spectrosc. 46, 707 (1992)] or a few shifted excitation wavelengths [Opt. Express 16, 10975 (2008)]. The purpose of the present work is to demonstrate a significant improvement of the efficacy of the modulated method by using different processing algorithms. The merits of each algorithm (Standard Deviation analysis, Fourier Filtering, Least-Squares fitting and Principal Component Analysis) are discussed and the dependence of the modulated Raman signal on several parameters, such as the amplitude and the modulation rate of the Raman excitation wavelength, is analyzed. The results of both simulation and experimental data demonstrate that Principal Component Analysis is the best processing algorithm. It improves the signal-to-noise ratio in the treated Raman spectra, reducing required acquisition times. Additionally, this approach does not require any synchronization procedure, reduces user intervention and renders it suitable for real-time applications. PMID- 20589000 TI - Motion detection using extended fractional Fourier transform and digital speckle photography. AB - Digital speckle photography is a useful tool for measuring the motion of optically rough surfaces from the speckle shift that takes place at the recording plane. A simple correlation based digital speckle photographic system has been proposed that implements two simultaneous optical extended fractional Fourier transforms (EFRTs) of different orders using only a single lens and detector to simultaneously detect both the magnitude and direction of translation and tilt by capturing only two frames: one before and another after the object motion. The dynamic range and sensitivity of the measurement can be varied readily by altering the position of the mirror/s used in the optical setup. Theoretical analysis and experiment results are presented. PMID- 20589001 TI - Analysis of a photoacoustic imaging system by the crosstalk matrix and singular value decomposition. AB - Photoacoustic imaging is a hybrid imaging modality capable of producing contrast similar to optical imaging techniques but with increased penetration depth and resolution in turbid media by encoding the information as acoustic waves. In general, it is important to characterize the performance of a photoacoustic imaging system by parameters such as sensitivity, resolution, and contrast. However, system characterization can extend beyond these metrics by implementing advanced analysis via the crosstalk matrix and singular value decomposition. A method was developed to experimentally measure a matrix that represented the imaging operator for a photoacoustic imaging system. Computations to produce the crosstalk matrix were completed to provide insight into the spatially dependent sensitivity and aliasing for the photoacoustic imaging system. Further analysis of the imaging operator was done via singular value decomposition to estimate the capability of the imaging system to reconstruct objects and the inherent sensitivity to those objects. The results provided by singular value decomposition were compared to SVD results from a de-noised imaging operator to estimate the number of measurable singular vectors for the system. These characterization techniques can be broadly applied to any photoacoustic system and, with regards to the studied system, could be used as a basis for improvements to future iterations. PMID- 20589002 TI - Compensation of motion artifacts in catheter-based optical frequency domain imaging. AB - A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter based imaging. PMID- 20589003 TI - Optical forces on small magnetodielectric particles. AB - We present a study of the optical force on a small particle with both electric and magnetic response, immersed in an arbitrary non-absorbing medium, due to a generic incident electromagnetic field. Expressions for the gradient force, radiation pressure and curl components are obtained for the force due to both the electric and magnetic dipoles excited in the particle. In particular, for the magnetic force we tentatively introduce the concept of curl of the spin angular momentum density of the magnetic field, also expressed in terms of 3D generalizations of the Stokes parameters. From the formal analogy between the conservation of momentum and the optical theorem, we discuss the origin and significance of the self-interaction force between both dipoles; this is done in connection with that of the angular distribution of scattered light and of the extinction cross section. PMID- 20589004 TI - Optical ridge waveguides preserving the thermo-optic features in LiNbO3 crystals fabricated by combination of proton implantation and selective wet etching. AB - We report on a new, simple method to fabricate optical ridge waveguides in a z cut LiNbO3 wafer by using proton implantation and selective wet etching. The measured modal field is well confined in the ridge waveguide region, which is also confirmed by the numerical simulation. With thermal annealing treatment at 400 degrees C, the propagation loss of the ridge waveguides is determined to be as low as approximately 0.9 dB/cm. In addition, the measured thermo-optic coefficients of the waveguides are in good agreement with those of the bulk, suggesting potential applications in integrated photonics. PMID- 20589005 TI - Direct measurement of electric-field-induced birefringence in a polymer stabilized blue-phase liquid crystal composite. AB - We demonstrate a method to directly measure the electric-field-induced birefringence of a polymer-stabilized blue-phase liquid crystal (PS-BPLC) composite. The induced birefringence follows the extended Kerr effect well and is approximately 3X the ordinary refractive index change. The measured data are validated by comparing the simulated and measured voltage-dependent transmittance with an in-plane switching cell. The impact of these results to the material optimization of emerging BPLC displays is discussed. PMID- 20589006 TI - Sensitivity increase for coating thickness determination using THz waveguides. AB - We report on layer thickness determination down to a thickness of 2.5 microns using terahertz waveguide spectroscopy. Compared to typical single-pass transmission measurements in the time domain, the effective THz pulse delay is considerably increased for a given layer thickness by using the high filling factor of the THz waveguide. This corresponds to a sensitivity increase up to a factor of 50 for the measured delay, allowing the direct measurement of layer thicknesses down to below hundredths of a THz wavelength. PMID- 20589007 TI - Intrinsic temperature sensitivity of tilted fiber Bragg grating based surface plasmon resonance sensors. AB - A miniature surface plasmon resonance sensor is fabricated from a gold-coated standard optical fiber with an in-core tilted fiber Bragg grating fabricated by UV exposure. The sensor has a measured refractive index sensitivity of 571.5 nm/RIU (refractive index unit) at constant temperature. We show here that the intrinsic temperature sensitivity of this device is reduced to less than 6.3 pm/degrees C (between 23 degrees C and 59 degrees C) when measurements are referenced to a core mode reflection resonance of the grating. This residual sensitivity is essentially that of the 50 nm thick deposited gold layer but it is bigger by one order of magnitude than the expected value (0.51 pm/degrees C) for a gold-water interface. PMID- 20589008 TI - 2D label-free imaging of resonant grating biochips in ultraviolet. AB - 2D images of label-free biochips exploiting resonant waveguide grating (RWG) are presented. They indicate sensitivities on the order of 1 pg/mm2 for proteins in air, and hence 10 pg/mm2 in water can be safely expected. A 320x256 pixels Aluminum-Gallium-Nitride-based sensor array is used, with an intrinsic narrow spectral window centered at 280 nm. The additional role of characteristic biological layer absorption at this wavelength is calculated, and regimes revealing its impact are discussed. Experimentally, the resonance of a chip coated with protein is revealed and the sensitivity evaluated through angular spectroscopy and imaging. In addition to a sensitivity similar to surface plasmon resonance (SPR), the RWGs resonance can be flexibly tailored to gain spatial, biochemical, or spectral sensitivity. PMID- 20589009 TI - Vibrational sum frequency generation spectroscopy using inverted visible pulses. AB - We present a broadband vibrational sum frequency generation (BB-VSFG) scheme using a novel ps visible pulse shape. We generate the fs IR pulse via standard procedures and simultaneously generate an 'inverted' time-asymmetric narrowband ps visible pulse via second harmonic generation in the pump depletion regime using a very long nonlinear crystal which has high group velocity mismatch (LiNbO3). The 'inverted' ps pulse shape minimally samples the instantaneous nonresonant response but maximally samples the resonant response, maintaining high spectral resolution. We experimentally demonstrate this scheme, presenting SFG spectra of canonical organic monolayer systems in the C-H stretch region (2800-3000 cm(-1)). PMID- 20589010 TI - Reference optical phantoms for diffuse optical spectroscopy. Part 1--Error analysis of a time resolved transmittance characterization method. AB - Development, production quality control and calibration of optical tissue mimicking phantoms require a convenient and robust characterization method with known absolute accuracy. We present a solid phantom characterization technique based on time resolved transmittance measurement of light through a relatively small phantom sample. The small size of the sample enables characterization of every material batch produced in a routine phantoms production. Time resolved transmittance data are pre-processed to correct for dark noise, sample thickness and instrument response function. Pre-processed data are then compared to a forward model based on the radiative transfer equation solved through Monte Carlo simulations accurately taking into account the finite geometry of the sample. The computational burden of the Monte-Carlo technique was alleviated by building a lookup table of pre-computed results and using interpolation to obtain modeled transmittance traces at intermediate values of the optical properties. Near perfect fit residuals are obtained with a fit window using all data above 1% of the maximum value of the time resolved transmittance trace. Absolute accuracy of the method is estimated through a thorough error analysis which takes into account the following contributions: measurement noise, system repeatability, instrument response function stability, sample thickness variation refractive index inaccuracy, time correlated single photon counting system time based inaccuracy and forward model inaccuracy. Two sigma absolute error estimates of 0.01 cm(-1) (11.3%) and 0.67 cm(-1) (6.8%) are obtained for the absorption coefficient and reduced scattering coefficient respectively. PMID- 20589011 TI - Ultra-smooth lithium niobate photonic micro-structures by surface tension reshaping. AB - Annealing of micro-structured lithium niobate substrates at temperatures close to, but below the melting point, allows surface tension to reshape preferentially melted surface zones of the crystal. The reshaped surface re-crystallizes upon cooling to form a single crystal again as it is seeded by the bulk which remains solid throughout the process. This procedure yields ultra-smooth single crystal superstructures suitable for the fabrication of photonic micro-components with low scattering loss. PMID- 20589012 TI - Ultrafast optical switching based on nonlinear polarization rotation in silicon waveguides. AB - We experimentally realize ultrafast all-optical switching in the 1.5-microm spectral region using cross-phase modulation inside a 5-mm long silicon waveguide. Modulation depths of up to 90% and switching window durations approximately 1 ps are achieved using 500-fs pump pulses with energies below 10 pJ. PMID- 20589013 TI - Widely tunable electro-optic distributed Bragg reflector in liquid crystal waveguide. AB - We propose and numerically investigate a versatile and easy-to-realize configuration for a guided-wave voltage-tunable distributed feedback grating based on reorientation in nematic liquid crystal and coplanar comb electrodes. The device has a wide tuning range exceeding 100 nm and covers C and L bands for wavelength division multiplexing. PMID- 20589014 TI - Study of relaxation oscillations in continuous-wave intracavity Raman lasers. AB - We study the relaxation oscillations in a continuous-wave intracavity Raman laser both theoretically and experimentally. Analytic expressions for the relaxation oscillation frequency are derived from the rate-equations and are validated by experiments. We show that some important experimental parameters such as the effective Raman gain coefficient and intracavity Stokes loss can be determined simply by measuring the relaxation oscillation frequency versus pump power. PMID- 20589016 TI - Polarization angle control of coherent coupling in metamaterial superlattice for closed mode excitation. AB - A superlattice structure of planar metamaterial is fabricated, where the orientation of double-split ring resonators is altered in a periodic way. A time domain terahertz transmission spectrum shows an enhanced Q-factor resonance appears when a closed mode is selectively excited by angular tuning of polarization direction. The polarization-angle selective resonance in metamaterial superlattice has a potential application in the selective field enhancement for spectroscopy. PMID- 20589015 TI - Broadband cloaking and mirages with flying carpets. AB - This paper extends the proposal of Li and Pendry [Phys. Rev. Lett. 101, 203901-4 (2008)] to invisibility carpets for infinite conducting planes and cylinders (or rigid planes and cylinders in the context of acoustic waves propagating in a compressible fluid). Carpets under consideration here do not touch the ground: they levitate in mid-air (or float in mid-water), which leads to approximate cloaking for an object hidden underneath, or touch either sides of a square cylinder on, or over, the ground. The tentlike carpets attached to the sides of a square cylinder illustrate how the notion of a carpet on a wall naturally generalizes to sides of other small compact objects. We then extend the concept of flying carpets to circular cylinders and show that one can hide any type of defects under such circular carpets, and yet they still scatter waves just like a smaller cylinder on its own. Interestingly, all these carpets are described by non-singular parameters. To exemplify this important aspect, we propose a multi layered carpet consisting of isotropic homogeneous dielectrics rings (or fluids with constant bulk modulus and varying density) which works over a finite range of wavelengths. PMID- 20589017 TI - A systematic method for designing depth-fused multi-focal plane three-dimensional displays. AB - Lack of accurate focus cues in conventional stereoscopic displays has potentially significant effects on depth perception accuracy and visual fatigue. Recently several multi-focal plane display prototypes have been demonstrated with the promise of improving the accuracy of focus cue rendering in stereoscopic displays. In this paper, we present a systematic method to address two fundamental issues in designing a multi-focal plane display: (1) the appropriate dioptric spacing between adjacent focal planes; and (2) the depth-weighted fusing function to render a continuous three-dimensional (3-D) volume using a sparse number of focal planes placed in the space. By taking account of both ocular factors of the human visual system (HVS) and display factors of a multi-focal plane system, we determine that an appropriate spacing between two adjacent focal planes should be ~0.6 diopter (D) while a smaller spacing may be necessary for further improving retinal image quality. We further develop a set of nonlinear depth-weighted fusing function with the promise of balancing perceptual continuity of a 3-D scene and retinal image quality. Our method was based on quantitative evaluation of the modulation transfer functions (MTF) of depth-fused images formed on retina. PMID- 20589018 TI - Automatic image performance balancing in lens optimization. AB - In the final stage of lens design, it is usually a critical step to balance the optical performance of a lens system across the sampled fields, which is achieved by adjusting the weights to these fields. Because the current optical design software packages use fixed weights in the optimization process, the task of weight adjustment is left to the optical designer, who has to change the weights manually after each optimization trail. However, this process may take a very long time to finish, especially when many fields of the lens system are sampled, and the results are subjectively affected by the designer's design experience. In this paper, we propose an automatic performance balancing method. An automatic outer loop is added in the optimization process. The weight for each sampled field and azimuth is calculated appropriately according to the actual performance of the current design and the system requirements, and it is applied to the corresponding field and azimuth automatically in the next optimization trial. The method is successfully implemented in CODE V, and design examples show that it is very effective. PMID- 20589019 TI - Characteristics of plasmonic Bragg reflectors with insulator width modulated in sawtooth profiles. AB - We present a new metal-insulator-metal (MIM)-based plasmonic Bragg reflector (PBR) design that solves the technical problems of conventional step profile MIM PBRs through the use of sawtooth profiles. Our numerical study revealed that the sawtooth PBRs exhibit lower insertion loss, narrower bandgap, and reduced rippling in the transmission spectrum when compared with the step PBRs. The defect mode of the sawtooth PBR also exhibits a higher transmission, narrower linewidth, and higher Q-factor. PMID- 20589020 TI - Evolution of the pairs of ultracold Rydberg atoms in the repulsive potential. AB - We present the explicit dynamics process of Rydberg cesium atoms initially experiencing a repulsive van der Waals (vdW) interaction by measuring the line width and intensity of the Rydberg ionization spectra. The signals of Rydberg atoms and free ions are recorded simultaneously within an initial 3.5 micros delay time between the excitation laser and the ramp electric field. For high density gases, a rapid decrease of Rydberg atoms and an increase of free ions are observed, which is not found to be the case for low-density gases. The experimental results indicate that superradiance is the main cause of the redistribution of Rydberg atoms from the repulsive potential to the attractive potential for high density, which provides the initial ionization. The corresponding theoretical calculation is also given. PMID- 20589021 TI - High resolution multimodal clinical ophthalmic imaging system. AB - We developed a multimodal adaptive optics (AO) retinal imager which is the first to combine high performance AO-corrected scanning laser ophthalmoscopy (SLO) and swept source Fourier domain optical coherence tomography (SSOCT) imaging modes in a single compact clinical prototype platform. Such systems are becoming ever more essential to vision research and are expected to prove their clinical value for diagnosis of retinal diseases, including glaucoma, diabetic retinopathy (DR), age related macular degeneration (AMD), and retinitis pigmentosa. The SSOCT channel operates at a wavelength of 1 microm for increased penetration and visualization of the choriocapillaris and choroid, sites of major disease activity for DR and wet AMD. This AO system is designed for use in clinical populations; a dual deformable mirror (DM) configuration allows simultaneous low- and high-order aberration correction over a large range of refractions and ocular media quality. The system also includes a wide field (33 deg.) line scanning ophthalmoscope (LSO) for initial screening, target identification, and global orientation, an integrated retinal tracker (RT) to stabilize the SLO, OCT, and LSO imaging fields in the presence of lateral eye motion, and a high-resolution LCD-based fixation target for presentation of visual cues. The system was tested in human subjects without retinal disease for performance optimization and validation. We were able to resolve and quantify cone photoreceptors across the macula to within approximately 0.5 deg (approximately 100-150 microm) of the fovea, image and delineate ten retinal layers, and penetrate to resolve features deep into the choroid. The prototype presented here is the first of a new class of powerful flexible imaging platforms that will provide clinicians and researchers with high resolution, high performance adaptive optics imaging to help guide therapies, develop new drugs, and improve patient outcomes. PMID- 20589022 TI - Theoretical aspects of Fourier Transform Spectrometry and common path triangular interferometers. AB - Recent investigations have induced relevant advancements of imaging interferometry, which is becoming a viable option for Earth remote sensing. Various research programs have chosen the Sagnac configuration for new imaging interferometers. Due to the growing diffusion of this technique, we have developed a self-contained theory for describing the signal produced by triangular FTSs and its optimal processing. We investigate the relevant disadvantages of multiplexing, and compare dispersive with FTS instruments. The paper addresses some methods for correcting the phase error, and the non-unitary transformation performed by a Sagnac interferometer. The effect of noise on spectral estimations is discussed. PMID- 20589023 TI - Hybrid planar microresonators with organic and InGaAs active media. AB - The authors report on the fabrication of hybrid planar micro-resonators based on InGaAs microdisks with an evaporated organic material. Samples of InGaAs grown on InP(100) substrates are obtained by Chemical Beam Epitaxy, and microdisks of InGaAs with different diameters are fabricated by focused ion beam. The hybrid disks are obtained by the subsequent evaporation of 8-hydroxyquinoline aluminium doped with 4-Dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran on the InGaAs microdisks. The devices, characterized by micro- and confocal photoluminescence imaging and spectroscopy, exhibit emission around 650 nm, from the organic material for disks with different radius. Finally, simultaneous emission in the visible and at whispering gallery resonant modes in the 1350-1450 nm range are observed due to excitation transfer to InGaAs. These devices open the possibility to combine the flexibility of organics with the high gain of III V compounds for wavelength down conversion and telecom applications. PMID- 20589024 TI - Simultaneous demodulation and demultiplexing of multi-rate WDM DPSK signals using a programmable wavelength-selective switch. AB - We show demodulation and demultiplexing of multi-channel WDM differential phase shift-keying (DPSK) signals operating simultaneously at 10 Gb/s and 40 Gb/s using a 1x4 wavelength selective switch. We achieve error-free performance for four channels equally spaced by 100 GHz propagated over an 85 km dispersion compensated link. We study the advantages and limitations of this new DPSK demodulator compared with the conventional delay-line interferometer. PMID- 20589025 TI - Molecular high harmonic generation in a two-color field. AB - We experimentally investigate the high harmonic generation (HHG) from CH4 molecules and Xe atoms in a two-color field (using the 800 nm laser and the tunable laser with the longer wavelength from 1500 nm to 1900 nm), and observe that the longer wavelength component can destructively suppress the HHG from CH4 molecules. By controlling the time delay between the two color laser pulses or tuning the laser intensity of the longer wavelength component, the suppressions of the HHG from CH4 molecules and the enhancements of the HHG from Xe atoms at the same laser condition are observed. The results indicate that the longer wavelength component around the molecular infrared absorption can suppress the molecular HHG process. PMID- 20589026 TI - Light-bullet routing and control with planar waveguide arrays. AB - Spatial mode-locking in three dimensions can be achieved in a slab waveguide array architecture. This study focuses on using the resulting robust and self starting light bullet formation for photonics applications. Specifically, light bullets can be manipulated through a simple electronically addressable spatial gain dynamics. By applying gain ramps in time and/or space via electronics technology, complete control and manipulation of the light bullets can be achieved, thus allowing for the construction of the master logic gates of NAND and NOR. Its robustness, self-starting behavior and easy addressability suggest that the slab waveguide array mode-locking merits serious consideration as a next generation photonics device. PMID- 20589027 TI - Planar focusing elements using spatially varying near-resonant aperture arrays. AB - Resonances in subwavelength apertures are accompanied by wavelength-dependent phase shifts in the transmitted fields offering a potential for manipulation of wavefields. Here, we present Finite Element Method simulations and experiments investigating light passing through arrays of nanometric spatially varying near resonant slits perforated in a silver film. We demonstrate that a one-dimensional focusing element can be obtained by tailoring the phase across the device through varying slit sizes around the resonant dimensions for a particular design wavelength. PMID- 20589028 TI - Very broad gain bandwidth parametric amplification in nonlinear crystals at critical wavelength degeneracy. AB - Gain spectra were calculated at critical wavelength degeneracy (CWD) in a collinear phase-matching geometry optical parametric amplification (OPA) process. The frequency bandwidth available through CWD-OPA is broader compared to the gain bandwidth obtained by the non-collinear OPA geometry. A solution for very broad bandwidth chirped pulse amplification based on partially deuterated DKDP (P-DKDP) crystals, pumped by pulsed green lasers, is proposed. 1.38x10(14) Hz frequency bandwidth and peak intensity gain G approximately 62 were calculated in a 5-mm long 58% deuterated DKDP crystal, pumped by 527-nm wavelength at 64-GW/cm2 intensity. Parametric amplification at CWD in few-mm thin P-DKDP crystals, pumped by picosecond pulses of nearly 100-GW/cm2 intensity, possesses a true potential for generating high energy laser pulses compressible to one-cycle duration. PMID- 20589029 TI - Wideband spectral compression of wavelength-tunable ultrashort soliton pulse using comb-profile fiber. AB - We demonstrated spectral compression of ultrashort soliton pulses in a wide wavelength region based on an adiabatic soliton spectral compression technique using a comb-profile fiber. The comb-profile fiber was carefully designed using numerical analysis and fabricated using a conventional single-mode fiber and a dispersion-shifted fiber. The spectral width of a 200 fs soliton pulse was compressed from 12 to 15 nm to 0.54-0.71 nm in the wavelength region 1620-1850 nm, giving a spectral compression factor of up to 19.8-25.9. Owing to the soliton effect, the side lobe level was suppressed to -19.2 to -9.7 dB. PMID- 20589030 TI - Low-loss compact high-Q 3D THz grating resonator based on a hybrid silicon metallic slit waveguide. AB - We present a high-Q 3D waveguide transmission filter for the THz-domain, based on an inhomogeneous Bragg grating, incorporated into the walls of a metallic slit waveguide. The reasons for the occurring loss mechanisms in the compact component are presented and the losses are minimized by selective mode adaptation and by tapering the transitions to the corrugated regions. The performance of the device and the influence of parameter variations are analyzed by detailed numerical simulations. These 3D simulations clearly show the drastic drawback of 2D calculations in designing narrowband 3D metal-dielectric waveguide filters and could even lead to a better performance than known designs in 2D technology. PMID- 20589031 TI - SiC avalanche photodiode array with microlenses. AB - A simple technique to incorporate microlenes with small photodiode arrays is demonstrated and analyzed. Using this method, the fill factor was increased from 2.6% to 22.4% for a two by two array. Simulation results are also shown. The photocurrent with microlens was approximately 8.6 times larger than without the microlens, which is consistent with simulation results. PMID- 20589032 TI - Self-mixing flow sensor using a monolithic VCSEL array with parallel readout. AB - The self-mixing sensing technique is a compact, interferometric sensing technique that can be used for measuring fluid flows. In this work, we demonstrate a parallel readout self-mixing flow velocity sensing system based on a monolithic Vertical-Cavity Surface-Emitting Laser (VCSEL) array. The parallel sensing scheme enables high-resolution full-field imaging systems employing electronic scanning with faster acquisition rates than mechanical scanning systems. The self-mixing signal is acquired from the variation in VCSEL junction voltage, thus markedly reducing the system complexity. The system was validated by measuring velocity distribution of fluid in a custom built diverging-converging planar flow channel. The results obtained agree well with simulation and demonstrate the feasibility of high frame-rate and resolution parallel self-mixing sensors. PMID- 20589033 TI - Conductor-gap-silicon plasmonic waveguides and passive components at subwavelength scale. AB - Subwavelength conductor-gap-silicon plasmonic waveguides along with compact S bends and Y-splitters were theoretically investigated and experimentally demonstrated on a silicon-on-insulator platform. A thin SiO2 gap between the conductor layer and silicon core provides subwavelength confinement of light while a long propagation length of 40 microm was achieved. Coupling of light between the plasmonic and conventional silicon photonic waveguides was also demonstrated with a high efficiency of 80%. The compact sizes, low loss operation, efficient input/output coupling, combined with a CMOS-compatible fabrication process, make these conductor-gap-silicon plasmonic devices a promising platform for realizing densely-integrated plasmonic circuits. PMID- 20589034 TI - Pixel-isolation liquid crystals formed by polarization-selective UV-curing of a prepolymer containing cinnamate oligomer. AB - A pixel isolated liquid crystal display was fabricated by polarization-selective anisotropic photoreaction of a prepolymer containing a cinnamate oligomer. The cinnamate oligomer was mainly distributed on the surface region of a UV-cured polymer wall. Anisotropic photo-dimerization of cinnamate moiety was achieved by polarized UV exposure. It was found that the polymer walls containing cinnamate dimers formed by polarized UV exposure showed ordered orientation of LC molecules at the boundary of the polymer walls resulting in electro-optic performance improvement. PMID- 20589035 TI - Fresnel coherent diffraction tomography. AB - Tomographic coherent imaging requires the reconstruction of a series of two dimensional projections of the object. We show that using the solution for the image of one projection as the starting point for the reconstruction of the next projection offers a reliable and rapid approach to the image reconstruction. The method is demonstrated on simulated and experimental data. This technique also simplifies reconstructions using data with curved incident wavefronts. PMID- 20589036 TI - A versatile diffractive maskless lithography for single-shot and serial microfabrication. AB - We demonstrate a diffractive maskless lithographic system that is capable of rapidly performing both serial and single-shot micropatterning. Utilizing the diffractive properties of phase holograms displayed on a spatial light modulator, arbitrary intensity distributions were produced to form two and three dimensional micropatterns/structures in a variety of substrates. A straightforward graphical user interface was implemented to allow users to load templates and change patterning modes within the span of a few minutes. A minimum resolution of approximately 700 nm is demonstrated for both patterning modes, which compares favorably to the 232 nm resolution limit predicted by the Rayleigh criterion. The presented method is rapid and adaptable, allowing for the parallel fabrication of microstructures in photoresist as well as the fabrication of protein microstructures that retain functional activity. PMID- 20589037 TI - Spatial distribution of absorption in plasmonic thin film solar cells. AB - The spatial dependence of absorption in a structured thin film solar cell is investigated through the rigorous coupled-wave analysis method. The investigated structure allows strong localized surface plasmon and surface plasmon polaritons, simultaneously. The absorptance of silver and amorphous silicon can be separately accounted for by calculating the time-averaged energy dissipation although only the absorption of amorphous silicon contributes to the photocurrent. In our studied case, the metallic material absorbs around 15%-20% of the total impinging sunlight while the active layer absorbs only approximately 50%. PMID- 20589038 TI - Real-time 4D signal processing and visualization using graphics processing unit on a regular nonlinear-k Fourier-domain OCT system. AB - We realized graphics processing unit (GPU) based real-time 4D (3D+time) signal processing and visualization on a regular Fourier-domain optical coherence tomography (FD-OCT) system with a nonlinear k-space spectrometer. An ultra-high speed linear spline interpolation (LSI) method for lambda-to-k spectral re sampling is implemented in the GPU architecture, which gives average interpolation speeds of >3,000,000 line/s for 1024-pixel OCT (1024-OCT) and >1,400,000 line/s for 2048-pixel OCT (2048-OCT). The complete FD-OCT signal processing including lambda-to-k spectral re-sampling, fast Fourier transform (FFT) and post-FFT processing have all been implemented on a GPU. The maximum complete A-scan processing speeds are investigated to be 680,000 line/s for 1024 OCT and 320,000 line/s for 2048-OCT, which correspond to 1GByte processing bandwidth. In our experiment, a 2048-pixel CMOS camera running up to 70 kHz is used as an acquisition device. Therefore the actual imaging speed is camera- limited to 128,000 line/s for 1024-OCT or 70,000 line/s for 2048-OCT. 3D Data sets are continuously acquired in real time at 1024-OCT mode, immediately processed and visualized as high as 10 volumes/second (12,500 A-scans/volume) by either en face slice extraction or ray-casting based volume rendering from 3D texture mapped in graphics memory. For standard FD-OCT systems, a GPU is the only additional hardware needed to realize this improvement and no optical modification is needed. This technique is highly cost-effective and can be easily integrated into most ultrahigh speed FD-OCT systems to overcome the 3D data processing and visualization bottlenecks. PMID- 20589039 TI - Particle tracking stereomicroscopy in optical tweezers: control of trap shape. AB - We present an optical system capable of generating stereoscopic images to track trapped particles in three dimensions. Two-dimensional particle tracking on each image yields three dimensional position information. Our approach allows the use of a high numerical aperture (NA=1.3) objective and large separation angle, such that particles can be tracked axially with resolution of 3 nm at 340 Hz. Spatial Light Modulators (SLMs), the diffractive elements used to steer and split laser beams in Holographic Optical Tweezers, are also capable of more general operations. We use one here to vary the ratio of lateral to axial trap stiffness by changing the shape of the beam at the back aperture of the microscope objective. Beams which concentrate their optical power at the extremes of the back aperture give rise to much more efficient axial trapping. The flexibility of using an SLM allows us to create multiple traps with different shapes. PMID- 20589040 TI - Silicon-based plasmonic waveguides. AB - We propose and comprehensively investigate Si-based plasmonic waveguides as a means to confine and manipulate photonic signals. The high refractive index of Si assures strong confinement and a very high level of photonic integration with achievable waveguide separations of the order of 10 nm and waveguide bends with 500 nm radius at telecommunication wavelengths, while using Al and Cu plasmonic material platforms, makes such waveguides fully compatible with existing CMOS fabrication processes. Their potential future in hybrid electronic/photonic chips is further reinforced as various configurations have been shown to compensate SPP propagation loss. The group velocity dispersion of such waveguides allows over 10 Tb/s signal transfer rates. The figures of merit allowing comparison of passive and active functionalities achievable with various waveguides have also been introduced. PMID- 20589041 TI - Enhanced visualization of oral cavity for early inflamed tissue detection. AB - We describe a color image reconstruction method that enables both direct visualization and direct digital image acquisition from one oral tissue by using various light sources and color compensating filters. In this method, the image of the oral tissue with white light emitting diodes (LEDs) with blue color compensating filter has a larger color difference between the normal and inflamed tissues. The enhanced visualization comes from the white light color mixing between the red normal tissue and bluish white light from the LEDs. With our method, we evaluate the perceived tissue reflectance in each pixel of the image and color reproduction with different illuminated spectra. Our approach to enhancement of visually perceived color difference between normal and inflamed oral tissue involves optimization of illumination and observation conditions by allowing a significant optical contrast of illuminated spectrum to reach the observer's eyes. In comparison with a conventional daylight LED flashlight, a LED with blue filter as the illuminant for oral cavity detection enhances the color difference between normal and inflamed tissues by 32%. PMID- 20589042 TI - Subwavelength broadband splitters and switches for femtosecond plasmonic signals. AB - Numerical simulations and an analytic approach based on transmission line theory are used to design splitters for nano-plasmonic signal processing that allow to arbitrarily adjust the ratio of transmission from an input into two different output arms. By adjusting the geometrical parameters of the structure, either a high bandwidth or a sharp transmission resonance is obtained. Switching between the two arms can be achieved by modulating the effective refractive index of the waveguide. Employing the instantaneous Kerr effect, switching rates in the THz regime are potentially feasible. The suggested devices are of interest for future applications in nanoplasmonic information processing. PMID- 20589043 TI - High-response ultraviolet photodetector based on N,N'-bis(naphthalen-1-yl)-N,N' bis(phenyl)benzidine and 2-(4-tertbutylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole. AB - A high-performance heterojunction ultraviolet (UV) photodetector based on N,N' bis(naphthalen-1-yl)-N,N'-bis(phenyl)ben-zidine (NPB) and 2-(4-tertbutylphenyl)-5 (4-biphenylyl)-1,3,4-oxadiazole (PBD) has been fabricated. The J-V characteristic curves of the device demonstrate a more than 4 orders of magnitude difference when illuminated under a 350 nm UV light and in the dark at +3 V. The device exhibits high sensitivity in the 300-420 nm region with the peak located around 350 nm. A high photocurrent response of 4.5 A/W at +3 V under an incident intensity of 60 microW/cm2 was achieved. These results indicate that the NPB/PBD heterojunction structure device might be used as low-cost UV photodetectors. PMID- 20589044 TI - Performances improvement in radio over fiber link through carrier suppression using Stimulated Brillouin scattering. AB - The performances of radio-over-fiber (RoF) link with fixed incident optical power on photodetector (PD) are improved through carrier suppression method. Firstly, a precise analytical model is proposed to quantify the relationship between the improvement of link gain, noise figure (NF), spur-free dynamic range (SFDR) and the carrier suppression ratio x, in which, the modulation index m is fully considered for the first time to our knowledge. Then the optimum optical carrier to-sideband ratio (CSR) for RoF link performances in both double-sideband and single-sideband modulation is obtained from the optimum x for the link performances. Finally the experiments with the carrier subtraction method realized by Stimulated Brillouin scattering (SBS) are carried out and the experimental results show good agreement with the simulation ones. PMID- 20589045 TI - Experimental study of the relation between the degrees of coherence in space-time and space-frequency domain. AB - We present an experimental study showing the effect of the change in the bandwidth of light on the magnitude of both the complex degree of coherence and the spectral degree of coherence at a pair of points in the cross-section of a beam. A variable bandwidth source with a Young's interferometer is utilized to produce the interference fringes. We also report for the first time that if the field is quasi-monochromatic or sufficiently narrowband, the elements of both the beam coherence polarization matrix and the cross-spectral density matrix, normalized to intensities (spectral densities) at the two points possess identical values. PMID- 20589046 TI - Integrated 2D photonic crystal stack filter fabricated using nanoreplica molding. AB - The design, fabrication, and characterization of an integrated 2D photonic crystal stack are described for application as optical filters with improved optical density and angle tolerance compared to single photonic crystal slabs. The 2D photonic crystals are designed as polarization independent reflectance filters with a narrow spectral bandwidth centered at lambda=532 nm by utilizing the guided mode resonance effect. Up to three photonic crystal layers are vertically stacked upon a single plastic substrate by using repeated nanoreplica molding process steps, with no alignment required between stacked layers. The photonic crystal stack filters achieve optical density of 2.24 with an angular tolerance of 14.8 degrees. PMID- 20589047 TI - An integrated optic ethanol vapor sensor based on a silicon-on-insulator microring resonator coated with a porous ZnO film. AB - Optical structures fabricated on silicon-on-insulator technology provide a convenient platform for the implementation of highly compact, versatile and low cost devices. In this work, we demonstrate the promise of this technology for integrated low power and low cost optical gas sensing. A room temperature ethanol vapor sensor is demonstrated using a ZnO nanoparticle film as a coating on an SOI micro-ring resonator of 5 microm in radius. The local coating on the ring resonators is prepared from colloidal suspensions of ZnO nanoparticles of around 3 nm diameter. The porous nature of the coating provides a large surface area for gas adsorption. The ZnO refractive index change upon vapor adsorption shifts the microring resonance through evanescent field interaction. Ethanol vapor concentrations down to 100 ppm are detected with this sensing configuration and a detection limit below 25 ppm is estimated. PMID- 20589048 TI - Ultra-fast, high-precision image analysis for localization-based super resolution microscopy. AB - Localization-based super resolution microscopy holds superior performances in live cell imaging, but its widespread use is thus far mainly hindered by the slow image analysis speed. Here we show a powerful image analysis method based on the combination of the maximum likelihood algorithm and a Graphics Processing Unit (GPU). Results indicate that our method is fast enough for real-time processing of experimental images even from fast EMCCD cameras working at full frame rate without compromising localization precision or field of view. This newly developed method is also capable of revealing movements from the images immediately after data acquisition, which is of great benefit to live cell imaging. PMID- 20589049 TI - Optical coherence tomography axial resolution improvement by step-frequency encoding. AB - A novel technique for axial resolution improvement of Optical Coherence Tomography (OCT) systems is proposed. The technique is based on step-frequency encoding, using frequency shifting, of the OCT signal. A resolution improvement by a factor of approximately 7 is achieved without the need for a broader bandwidth light source. This method exploits a combination of two basic principles: the appearance of beating, when adding two signals of slightly different carrier frequencies, and the resolution improvement by deconvolution of the interferogram with an encoded autocorrelation function. In time domain OCT, step-frequency encoding can be implemented by performing two scans, with different carrier frequencies, and subsequently adding them to create the encoded signal. When the frequency steps are properly selected, deconvolution of the resulting interferogram, using appropriate kernels, results in a narrower resolution width. PMID- 20589050 TI - Electromagnetic localization based on transformation optics. AB - Localization of an electromagnetic field can be achieved by transformation optics using metamaterials. A coordinate transformation structure different from traditional resonator is proposed. Wherein, arbitrary frequency of the whole band of electromagnetic wave can be localized without energy loss, i.e., the modes in this structure are continuous. Theoretical analysis and numerical simulation show that the material parameter variations at the outer boundary of the structure have little influence on the localization property. When realizable physical structure is considered, multi-layer approximation should be applied. The calculated results show that the estimated localization time is about 100 ns for an 8-layer inhomogeneous approximation, and it could reach several seconds for a 30-layer homogeneous approximation. The present work may present a new application of transformation optics. PMID- 20589051 TI - Ultra-broadband one-to-two wavelength conversion using low-phase-mismatching four wave mixing in silicon waveguides. AB - An ultra-broadband wavelength conversion is presented and experimentally demonstrated based on nondegenerate four-wave mixing in silicon waveguides. Two idlers can be generated and their wavelengths can be freely tuned by using two pumps where the first pump is set close to the signal and the second pump is wavelength tunable. Using this scheme, a small phase-mismatch and hence an ultra broad conversion bandwidth is realized in spite of the waveguide dispersion profile. We show that the experimental demonstrations are consistent with the theoretical estimations. Total conversion bandwidth is estimated to reach >500 nm and it can provide a feasible approach to realize one-to-two wavelength conversion among different telecommunication bands between 1300 nm and 1800 nm. PMID- 20589052 TI - Deformable liquid droplets for optical beam control. AB - We demonstrate a liquid droplet whose surface profile can be reshaped by voltage. As the dielectric force increases, the dome of a liquid droplet could touch the top substrate and become flat. While the voltage is removed, the droplet recovers to its original spherical shape. By choosing proper liquids, the required voltage for such a shape change is relatively low and the transition speed is fast. Potential application of such a deformable droplet for optical beam control is discussed. PMID- 20589053 TI - Transverse power flow reversing of guided waves in extreme nonlinear metamaterials. AB - We theoretically prove that electromagnetic beams propagating through a nonlinear cubic metamaterial can exhibit a power flow whose direction reverses its sign along the transverse profile. This effect is peculiar of the hitherto unexplored extreme nonlinear regime where the nonlinear response is comparable or even greater than the linear contribution, a condition achievable even at relatively small intensities. We propose a possible metamaterial structure able to support the extreme conditions where the polarization cubic nonlinear contribution does not act as a mere perturbation of the linear part. PMID- 20589054 TI - Second harmonic generation from nanocrystals under linearly and circularly polarized excitations. AB - We study second harmonic generation (SHG) from non-centrosymmetric nanocrystals under linearly polarized (LP) and circularly polarized (CP) excitations. Theoretical models are developed for SHG from nanocrystals under both plane-wave and focused excitations. We find that the focused excitation reduces the polarization dependency of the SHG signal. We show that the SHG response under CP excitation is generally inferior to the average of LP excitations over all orientations. We verify the theory by measuring the SHG polar responses from BaTiO3 nanocrystals with a scanning confocal microscope. The experimental data agrees well with the theory. PMID- 20589055 TI - Cavity-dumping of a semiconductor disk laser for the generation of wavelength tunable micro-Joule nanosecond pulses. AB - We report on cavity-dumping of a semiconductor disk laser as a method to generate energetic wavelength-tunable nanosecond pulses with repetition rates ranging from 0.1 to 4 MHz. Experimentally, emission of 24 ns pulses with peak output power of 41 W in a single beam output (and of 30 ns with peak power of 57 W in a combined beam output) with wavelength tuning from 1045 to 1080 nm was obtained. Numerical modeling is also introduced to provide more insight into the most important parameters controlling this mode of operation and to define optimization avenues. PMID- 20589056 TI - Double scattering of light from Biophotonic Nanostructures with short-range order. AB - We investigate the physical mechanism for color production by isotropic nanostructures with short-range order in bird feather barbs. While the primary peak in optical scattering spectra results from constructive interference of singly-scattered light, many species exhibit secondary peaks with distinct characteristic. Our experimental and numerical studies show that these secondary peaks result from double scattering of light by the correlated structures. Without an analog in periodic or random structures, such a phenomenon is unique for short-range ordered structures, and has been widely used by nature for non iridescent structural coloration. PMID- 20589057 TI - Light scattering induced by opposite microdomains in LiNbO3:Fe:Hf crystals. AB - We report on the light scattering phenomenon in annealed multidomain LiNbO3:Fe:Hf crystals. The scattering sources are found to be some fog-like "defects", which cause the polarization-dependent scattering of the light, and can be removed completely by the illumination of visible light. Based on these results and the etch patterns, these "defects" are suggested to be refractive index fluctuations induced by the space charges accumulated at the boundary of opposite microdomains. The influence of quick heating-up on the "defects" is also studied and the results firmly support our suggestion about the nature of the "defects". At last, the temporal curves of the transmitted intensity during the light scattering are explained. The mechanism for the opposite microdomain formation is also explained from the view of crystal growth. PMID- 20589058 TI - A force detection technique for single-beam optical traps based on direct measurement of light momentum changes. AB - Despite the tremendous success of force-measuring optical traps in recent years, the calibration methods most commonly used in the field have been plagued with difficulties and limitations. Force sensing based on direct measurement of light momentum changes stands out among these as an exception. Especially significant is this method's potential for working within living cells, with non-spherical particles or with non-Gaussian beams. However, so far, the technique has only been implemented in counter-propagating dual-beam traps, which are difficult to align and integrate with other microscopy techniques. Here, we show the feasibility of a single-beam gradient-trap system working with a force detection technique based on this same principle. PMID- 20589059 TI - Design of rectangular-groove fused-silica gratings as polarizing beam splitters. AB - The application of rectangular-groove fused-silica gratings as polarizing beam splitters (PBSs) under Littrow incidence is investigated. Based on the simple modal method, two different cases of PBS gratings are designed. The achieved solutions, which are independent on the incident wavelength, are verified by the rigorous coupled-wave analysis and expressed in several polynomials instead of listing one or two numerical solutions. More importantly, on the basis of the designed PBS gratings, a porous fused silica antireflective film is introduced to improve their performances. Theoretical results indicate that such modified rectangular-groove PBS gratings exhibit higher diffraction efficiencies (over 0.99) and larger spectral bandwidths. PMID- 20589060 TI - Surface-emitting mid-infrared quantum cascade lasers with high-contrast photonic crystal resonators. AB - We have developed surface-emitting single-mode quantum cascade lasers which employ high-contrast photonic-crystal resonators. The devices operate on band edge states of the photonic band-structure. The mode profile and polarization characteristics of the band-edge modes are calculated by three-dimensional finite difference time-domain simulation. Experimentally, the spectral properties, the far-field patterns, and the polarization characteristics of the lasers are determined and compared with simulations. The good agreement between the simulations and the experiments confirms that the hexapolar mode at the Gamma point band-edge gives rise to lasing. By using a novel and advanced fabrication method, deep and vertical PhC holes are fabricated with no metal redeposition on the sidewalls, which improves the laser performance with respect to the current status. The angular of the output beam is approximately 15 masculine, and the side mode suppression ratio of the single mode emission is about 25 dB. The threshold current density at 78 K and the maximum operation temperature are 7.6 kA/cm2 and 220 K, respectively. The performance is mainly limited by the loss induced by surface plasmon waveguide, which can be overcome by using an optimized dielectric waveguide structure. PMID- 20589061 TI - Incident-angle-insensitive and polarization independent polarization rotator. AB - This paper proposes a method to design an incident-angle-insensitive polarization independent polarization rotator. This polarization rotator is composed of layers of impedance-matched anisotropic metamaterial (IMAM) with each layer's optical axes gradually rotating an angle. Numerical simulation based on the generalized 4x4 transfer matrix method is applied, and the results reveal that the IMAM rotator is not only polarization-independent but also insensitive to the angle of incidence. A 90 degrees polarization rotation with tiny ellipticity variation is still available at a wide range of incident angles from 0 to 40 degrees, which is further confirmed with a microwave bi-split-ring resonator (bi-SRR) rotator. This may be valuable for the design of optoelectronic and microwave devices. PMID- 20589062 TI - Rectification of elemental image set and extraction of lens lattice by projective image transformation in integral imaging. AB - We propose a new method for rectifying a geometrical distortion in the elemental image set and extracting an accurate lens lattice lines by projective image transformation. The information of distortion in the acquired elemental image set is found by Hough transform algorithm. With this initial information of distortions, the acquired elemental image set is rectified automatically without the prior knowledge on the characteristics of pickup system by stratified image transformation procedure. Computer-generated elemental image sets with distortion on purpose are used for verifying the proposed rectification method. Experimentally-captured elemental image sets are optically reconstructed before and after the rectification by the proposed method. The experimental results support the validity of the proposed method with high accuracy of image rectification and lattice extraction. PMID- 20589063 TI - Low-loss semi-reflective in-fiber mirrors. AB - This paper presents a method for the efficient production of all-fiber semi reflective mirrors suitable for fiber sensors and other all-fiber device applications. The mirrors are obtained by the short duration etching of a standard single mode fiber in hydrofluoric acid, followed by an on-line feedback assisted fusion splicing process. Fiber mirror reflectance up to 9.5% with excess losses below 0.25 dB were produced in practice, which is in good agreement with provided theoretical and modeling analyses. Control over the etching time and fusion splicing process allows for balancing between reflectance and transmittance, while maintaining low excess loss of experimentally produced mirrors. PMID- 20589064 TI - Transformational plasmonics: cloak, concentrator and rotator for SPPs. AB - We adapt tools of transformation optics to surface plasmon polaritons (SPPs) propagating at the interface between two anisotropic media of opposite permittivity sign. We identify the role played by entries of anisotropic heterogeneous tensors of permittivity and permeability--deduced from a coordinate transformation--in the dispersion relation governing propagation of SPPs. We apply this concept to an invisibility cloak, a concentrator and a rotator for SPPs. PMID- 20589065 TI - Double image encryption by using iterative random binary encoding in gyrator domains. AB - We propose a double image encryption by using random binary encoding and gyrator transform. Two secret images are first regarded as the real part and imaginary part of complex function. Chaotic map is used for obtaining random binary matrix. The real part and imaginary part of complex function are exchanged under the control of random binary data. An iterative structure composed of the random binary encoding method is designed and employed for enhancing the security of encryption algorithm. The parameters in chaotic map and gyrator transform serve as the keys of this encryption scheme. Some numerical simulations have been made, to demonstrate the performance this algorithm. PMID- 20589066 TI - Therapeutics of diabetes mellitus: focus on insulin analogues and insulin pumps. AB - AIM: Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. RESULTS: Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed. CONCLUSIONS: Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID- 20589067 TI - Maintenance or emergence of chronic phase secondary cytotoxic T lymphocyte responses after loss of acute phase immunodominant responses does not protect SIV infected rhesus macaques from disease progression. AB - The simian immunodeficiency virus- (SIV-) infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. In this paper, we document the cytotoxic T lymphocyte (CTL) response to SIV and its effects on viral evolution in an effort to identify events associated with disease progression regardless of MHC allele expression. We observed the evolution of epitopes targeted by CTLs in a group of macaques that included long-term nonprogressing (LTNP), slowly progressing (SP), normally progressing (NP), and rapidly progressing (RP) animals. Collectively, our data (1) identify novel CTL epitopes from an SP animal that are not restricted by known protective alleles, (2) illustrate that, in this small study, RP and NP animals accrue more mutations in CTL epitopes than in SP or LTNP macaques, and (3) demonstrate that the loss of CTL responses to immunodominant epitopes is associated with viral replication increases, which are not controlled by secondary CTL responses. These findings provide further evidence for the critical role of the primary cell-mediated immune responses in the control of retroviral infections. PMID- 20589068 TI - Inborn errors of energy metabolism associated with myopathies. AB - Inherited neuromuscular disorders affect approximately one in 3,500 children. Structural muscular defects are most common; however functional impairment of skeletal and cardiac muscle in both children and adults may be caused by inborn errors of energy metabolism as well. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise intolerance, muscle pain, reversible or progressive muscle weakness, and myoglobinuria. In this review, the physiology of energy metabolism in muscle is described, followed by the presentation of distinct disorders affecting skeletal and cardiac muscle: glycogen storage diseases types III, V, VII, fatty acid oxidation defects, and respiratory chain defects (i.e., mitochondriopathies). The diagnostic work-up and therapeutic options in these disorders are discussed. PMID- 20589069 TI - Mathematical modeling: bridging the gap between concept and realization in synthetic biology. AB - Mathematical modeling plays an important and often indispensable role in synthetic biology because it serves as a crucial link between the concept and realization of a biological circuit. We review mathematical modeling concepts and methodologies as relevant to synthetic biology, including assumptions that underlie a model, types of modeling frameworks (deterministic and stochastic), and the importance of parameter estimation and optimization in modeling. Additionally we expound mathematical techniques used to analyze a model such as sensitivity analysis and bifurcation analysis, which enable the identification of the conditions that cause a synthetic circuit to behave in a desired manner. We also discuss the role of modeling in phenotype analysis such as metabolic and transcription network analysis and point out some available modeling standards and software. Following this, we present three case studies-a metabolic oscillator, a synthetic counter, and a bottom--up gene regulatory network--which have incorporated mathematical modeling as a central component of synthetic circuit design. PMID- 20589072 TI - Transformation of a cutaneous follicle center lymphoma to a diffuse large B-cell lymphoma-an unusual presentation. AB - Primary cutaneous follicle center lymphoma (PCFCL) is characterized by a proliferation of follicle center cells in the skin. A definitive diagnosis is frequently delayed because of difficulties in interpretation of the histopathologic findings. It has an excellent prognosis with a 5-year survival over 95% and its risk of transformation has not been established. We describe a case report of man with a gastric diffuse large B-cell lymphoma (DLBCL) referred to our clinic because of nodules in the back that had gradually developed over a period of 10 years. A biopsy performed 3 years before was interpreted as reactive follicular hyperplasia. A new skin biopsy revealed a diffuse large B-cell lymphoma and immunoglobulin heavy chain gene rearrangements from the initial skin biopsy (PCBCL) and the DLBCL gastric biopsy were studied by polymerase chain reaction and an identical clonal rearrangement was detected which was highly suggestive of a transformation lymphoma. PMID- 20589071 TI - Role of antimicrobial selective pressure and secondary factors on antimicrobial resistance prevalence in Escherichia coli from food-producing animals in Japan. AB - The use of antimicrobial agents in the veterinary field affects the emergence, prevalence, and dissemination of antimicrobial resistance in bacteria isolated from food-producing animals. To control the emergence, prevalence, and dissemination of antimicrobial resistance, it is necessary to implement appropriate actions based on scientific evidence. In Japan, the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) was established in 1999 to monitor the antimicrobial susceptibility of foodborne and commensal bacteria from food-producing animals. The JVARM showed that the emergence and prevalence of resistant Escherichia coli were likely linked to the therapeutic antimicrobial use in food-producing animals through not only direct selection of the corresponding resistance but also indirect selections via cross-resistance and coresistance. In addition, relevant factors such as host animals and bacterial properties might affect the occurrence and prevalence of antimicrobial resistant E. coli under the selective pressure from antimicrobial usage. This paper reviews the trends in antimicrobial resistance in E. coli and consumption of antimicrobials agents in Japan and introduces the relationship between antimicrobial usage and prevalence of antimicrobial-resistant bacteria, from food producing animals under the JVARM program. In this paper, we will provide the underlying information about the significant factors that can help control antimicrobial resistance in bacteria in veterinary medicine. PMID- 20589073 TI - Developmental stage-specific imprinting of IPL in domestic pigs (Sus scrofa). AB - Imprinted in placenta and liver (IPL) gene has been identified as an imprinted gene in the mouse and human. Its sequence and imprinting status, however, have not been determined in the domestic pigs. In the present study, a 259 base pair specific sequence for IPL gene of the domestic pig was obtained and a novel SNP, a T/C transition, was identified in IPL exon 1. The C allele of this polymorphism was found to be the predominant allele in Landrace,Yorkshire, and Duroc. The frequency of CC genotype and C allele are different in Duroc as compared with Yorkshire (P = .038 and P = .005, resp.). Variable imprinting status of this gene was observed in different developmental stages. For example, it is imprinted in 1 day old newborns (expressed from the maternal allele), but imprinting was lost in 180-day-old adult (expressed from both parental alleles). Real-time PCR analysis showed the porcine IPL gene is expressed in all tested eight organ/tissues. The expression level was significantly higher in spleen, duodenum, lung, and bladder of 180-day-old Lantang adult compared to that in 1-day-old newborns Lantang pigs (P < .05). In conclusion, the imprinting of the porcine IPL gene is developmental stage and tissue specific. PMID- 20589075 TI - The vectorial potential of Lutzomyia (Nyssomyia) intermedia and Lutzomyia (N.) whitmani in the transmission of Leishmania (V.) braziliensis can also be related to proteins attaching. PMID- 20589074 TI - A styrene-alt-maleic acid copolymer is an effective inhibitor of R5 and X4 human immunodeficiency virus type 1 infection. AB - An alternating copolymer of styrene and maleic acid (alt-PSMA) differs from other polyanionic antiviral agents in that the negative charges of alt-PSMA are provided by carboxylic acid groups instead of sulfate or sulfonate moieties. We hypothesized that alt-PSMA would have activity against human immunodeficiency virus type 1 (HIV-1) comparable to other polyanions, such as the related compound, poly(sodium 4-styrene sulfonate) (PSS). In assays using cell lines and primary immune cells, alt-PSMA was characterized by low cytotoxicity and effective inhibition of infection by HIV-1 BaL and IIIB as well as clinical isolates of subtypes A, B, and C. In mechanism of action assays, in which each compound was added to cells and subsequently removed prior to HIV-1 infection ("washout" assay), alt-PSMA caused no enhancement of infection, while PSS washout increased infection 70% above control levels. These studies demonstrate that alt PSMA is an effective HIV-1 inhibitor with properties that warrant further investigation. PMID- 20589070 TI - Proteomics of plant pathogenic fungi. AB - Plant pathogenic fungi cause important yield losses in crops. In order to develop efficient and environmental friendly crop protection strategies, molecular studies of the fungal biological cycle, virulence factors, and interaction with its host are necessary. For that reason, several approaches have been performed using both classical genetic, cell biology, and biochemistry and the modern, holistic, and high-throughput, omic techniques. This work briefly overviews the tools available for studying Plant Pathogenic Fungi and is amply focused on MS based Proteomics analysis, based on original papers published up to December 2009. At a methodological level, different steps in a proteomic workflow experiment are discussed. Separate sections are devoted to fungal descriptive (intracellular, subcellular, extracellular) and differential expression proteomics and interactomics. From the work published we can conclude that Proteomics, in combination with other techniques, constitutes a powerful tool for providing important information about pathogenicity and virulence factors, thus opening up new possibilities for crop disease diagnosis and crop protection. PMID- 20589076 TI - Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus. AB - Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading to IL10 and IL13 overexpression in SLE patients are not well understood. In this study, we confirm that the levels of both IL10 and IL13 mRNA in CD4+ T cells and of serum IL10 and IL13 proteins are increased in SLE patients. We show that the DNA methylation levels within IL10 and IL13 gene regulatory domains are reduced in SLE CD4+ T cells relative to healthy controls and negatively correlate with IL10 and IL13 mRNA expression. Moreover, treating healthy CD4+ T cells with the demethylating agent 5-azacytidine (5-azaC) increased IL10 and IL13 mRNA transcription. Together, our results show that promoter methylation is a determinant of IL10 and IL13 expression in CD4+ T cells, and we propose that DNA hypomethylation leads to IL10 and IL13 overexpression in SLE patients. PMID- 20589077 TI - New insights into the structural roles of nebulin in skeletal muscle. AB - One important feature of muscle structure and function that has remained relatively obscure is the mechanism that regulates thin filament length. Filament length is an important aspect of muscle function as force production is proportional to the amount of overlap between thick and thin filaments. Recent advances, due in part to the generation of nebulin KO models, reveal that nebulin plays an important role in the regulation of thin filament length. Another structural feature of skeletal muscle that is not well understood is the mechanism involved in maintaining the regular lateral alignment of adjacent sarcomeres, that is, myofibrillar connectivity. Recent studies indicate that nebulin is part of a protein complex that mechanically links adjacent myofibrils. Thus, novel structural roles of nebulin in skeletal muscle involve the regulation of thin filament length and maintaining myofibrillar connectivity. When these functions of nebulin are absent, muscle weakness ensues, as is the case in patients with nemaline myopathy with mutations in nebulin. Here we review these new insights in the role of nebulin in skeletal muscle structure. PMID- 20589078 TI - Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PMID- 20589079 TI - The roots of bioinformatics. PMID- 20589080 TI - Constraint-based model of Shewanella oneidensis MR-1 metabolism: a tool for data analysis and hypothesis generation. AB - Shewanellae are gram-negative facultatively anaerobic metal-reducing bacteria commonly found in chemically (i.e., redox) stratified environments. Occupying such niches requires the ability to rapidly acclimate to changes in electron donor/acceptor type and availability; hence, the ability to compete and thrive in such environments must ultimately be reflected in the organization and utilization of electron transfer networks, as well as central and peripheral carbon metabolism. To understand how Shewanella oneidensis MR-1 utilizes its resources, the metabolic network was reconstructed. The resulting network consists of 774 reactions, 783 genes, and 634 unique metabolites and contains biosynthesis pathways for all cell constituents. Using constraint-based modeling, we investigated aerobic growth of S. oneidensis MR-1 on numerous carbon sources. To achieve this, we (i) used experimental data to formulate a biomass equation and estimate cellular ATP requirements, (ii) developed an approach to identify cycles (such as futile cycles and circulations), (iii) classified how reaction usage affects cellular growth, (iv) predicted cellular biomass yields on different carbon sources and compared model predictions to experimental measurements, and (v) used experimental results to refine metabolic fluxes for growth on lactate. The results revealed that aerobic lactate-grown cells of S. oneidensis MR-1 used less efficient enzymes to couple electron transport to proton motive force generation, and possibly operated at least one futile cycle involving malic enzymes. Several examples are provided whereby model predictions were validated by experimental data, in particular the role of serine hydroxymethyltransferase and glycine cleavage system in the metabolism of one carbon units, and growth on different sources of carbon and energy. This work illustrates how integration of computational and experimental efforts facilitates the understanding of microbial metabolism at a systems level. PMID- 20589082 TI - Testicular hamartomas and epididymal tumor in a cowden disease: a case report. AB - Testicular hamartomas (TH) is a benign condition. An association of TH with Cowden disease (CD) is known. Ultrasound features of hamartomas are often diagnostic. We present a case of Cowden disease with TH and an epididymal tumor. Imaging features of TH and its differentials has been discussed. Although, association of Cowden disease with many malignancies have been documented, epididymal tumor has not been described. To our knowledge, this paper is the first to describe epididymal tumor in association with Cowden disease. PMID- 20589081 TI - TRANSAT-- method for detecting the conserved helices of functional RNA structures, including transient, pseudo-knotted and alternative structures. AB - The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular environment. PMID- 20589083 TI - Piperacillin-induced immune hemolytic anemia in an adult with cystic fibrosis. AB - We report a case of drug-induced immune hemolytic anemia (DIIHA) in an adult female with cystic fibrosis (CF), complicating routine treatment of a pulmonary exacerbation with intravenous piperacillin-tazobactam. Workup revealed a positive direct antiglobulin test (DAT) due to red blood cell (RBC)-bound IgG and C3 and piperacillin antibodies detectable in the patient's serum. The potential influence of CF transmembrane conductance regulator mutations on the severity of DIIHA is discussed. This report illustrates the importance of early identification of DIIHA, a rare complication of a commonly utilized medication in CF. PMID- 20589084 TI - An atypical etiology of suprasphincteric fistula: a forgotten surgical material. AB - While the majority of fistulas in ano result from infection of the anal crypts, complex, recurrent, and/or nonhealing fistulas should always raise the suspicion of a chronic underlying condition. In this paper, we present a 30-year-old male patient with a diagnosis of a complex suprasphincteric fistula caused by a surgical thread left behind after an orthopedic hip operation performed sixteen years ago. Partial fistulectomy, extraction of the foreign material, and debridement procedures were performed. Few cases of such complex fistulas in ano due to foreign materials have been described in the literature. After careful history-taking, meticulous physical examination under general anesthesia should be done in order to deal with this rare type of fistula. PMID- 20589085 TI - Short-term bisphosphonate therapy could ameliorate osteonecrosis: a complication in childhood hematologic malignancies. AB - Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture. PMID- 20589086 TI - Acute tension pneumothorax following cardiac herniation after pneumonectomy. AB - A tension pneumothorax is one of the main causes of cardiac arrest in the initial postoperative period after thoracic surgery. Tension pneumothorax and cardiac herniation must be taken into account in hemodynamically unstable patients after pneumonectomy. We report an unusual case of successful treatment of acute tension pneumothorax following cardiac herniation and intrathoracic bleeding after pneumonectomy. PMID- 20589087 TI - Traumatic pseudoaneurysm of the middle meningeal artery causing an intracerebral hemorrhage. AB - Traumatic aneurysms comprise less than 1% of all intracranial aneurysms. Most of these aneurysms are actually false aneurysms, or pseudoaneurysms, which are caused by the rupture of entire vessel wall layers, with the wall of the aneurysm being formed by the surrounding cerebral structures. Traumatic pseudoaneurysms of the middle meningeal artery are also rare. Only four cases have been reported in the literature with intracerebral hematoma. In this paper, the authors report a case of a patient with a ruptured traumatic pseudoaneurysm of the MMA who presented with an intracerebral hematoma in the left temporal region immediately after trauma; the patient underwent endovascular treatment. PMID- 20589088 TI - Lung cancer presenting as acrometastasis to the finger: a case report. AB - Lung cancer is the commonest cause of acrometastatic disease to the fingers. Here we describe a case of occult lung cancer presenting as unrelenting finger pain and swelling from a metastatic phalangeal fracture. The patient's management was largely palliative and he died soon after discovery of the primary tumor. Digital acrometastatic disease rarely becomes symptomatic before the primary lung cancer is diagnosed and, as observed in this case, carries a very poor prognosis. Clinicians should be cognizant of the strong association between digital acrometastases and bronchogenic carcinoma and vigilant in screening high-risk patients with importunate finger symptoms. PMID- 20589089 TI - Leiomyosarcoma arising in the pancreatic duct: a case report and review of the current literature. AB - Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained from chart review and interdepartmental collaboration. A mass in the tail of the pancreas was identified with large pleomorphic and spindle-shaped cells. Immunohistochemistry for vimentin, smooth muscle actin, and desmin was positive. All remaining immunohistochemical markers performed were negative. The tumor clearly originated from the pancreatic duct wall, filled and expanded the duct lumen, and was covered with a layer of benign biliary epithelium. Conclusion. Leiomyosarcoma of the pancreas is an extremely rare malignancy with few reported cases in the literature. The prognosis is poor, and treatment consists of alleviating symptoms and pain management. To our knowledge, this represents the first reported case demonstrating clear origin of a leiomyosarcoma from the pancreatic duct. PMID- 20589090 TI - Histologically malignant solitary fibrous tumour of the anterior thoracic wall: a case report and review of the literature. AB - Solitary fibrous tumour (SFT) is a rare oncological entity that most often arises in the pleura. Over the past 10 years, the tumour has been described at numerous extrapleural locations. We present the case of a 42-year-old female Caucasian patient with an extrapleural SFT located at the anterior thoracic wall for 22 years, with atypical histological characteristics and clinical features of malignancy. Management consisted of a wide surgical resection, plastic reconstruction, and postoperative radiotherapy. Although extrapleural SFT usually behaves as a benign soft tissue tumour, it can also present with a more aggressive local behavior, including locoregional recurrence or metastasis. In that case, a multidisciplinary approach is required for accurate diagnosis and proper management. PMID- 20589091 TI - Cervicothoracic intradural arachnoid cyst misdiagnosed as motor neuron disease. AB - Recognizing syndromes which mimic ALS is crucial both to avoid giving this diagnosis erroneously and since there may be appropriate treatments. We report a 63-year-old woman diagnosed with possible ALS five years ago based on upper and lower motor neuron signs with typical electrophysiology and normal cranial MRI. At reassessment, spinal MRI revealed a cervicothoracic cyst with cord compression that was successfully treated neurosurgically. Histopathology confirmed an arachnoid origin as suspected from MRI. Spinal cysts may mimic ALS and need to be thoroughly excluded by appropriate imaging. PMID- 20589092 TI - Ethanol and phencyclidine interact with respect to nucleus accumbens dopamine release: differential effects of administration order and pretreatment protocol. AB - Executive dysfunction is a common symptom among alcohol-dependent individuals. Phencyclidine (PCP) injection induces dysfunction in the prefrontal cortex of animals but little is known about how PCP affects the response to ethanol. Using the in vivo microdialysis technique in male Wistar rats, we investigated how systemic injection of 5 mg/kg PCP would affect the dopamine release induced by local infusion of 300 mM ethanol into the nucleus accumbens. PCP given 60 min before ethanol entirely blocked ethanol-induced dopamine release. However, when ethanol was administered 60 min before PCP, both drugs induced dopamine release and PCP's effect was potentiated by ethanol (180% increase vs 150%). To test the role of prefrontal cortex dysfunction in ethanol reinforcement, animals were pretreated for 5 days with 2.58 mg/kg PCP according to previously used 'PFC hypofunction protocols'. This, however, did not change the relative response to PCP or ethanol compared to saline-treated controls. qPCR illustrated that this low PCP dose did not significantly change expression of glucose transporters Glut1 (SLC2A1) or Glut3 (SLC2A3), monocarboxylate transporter MCT2 (SLC16A7), glutamate transporters GLT-1 (SLC1A2) or GLAST (SLC1A3), the immediate early gene Arc (Arg3.1) or GABAergic neuron markers GAT-1 (SLC6A1) and parvalbumin. Therefore, we concluded that PCP at a dose of 2.58 mg/kg for 5 days did not induce hypofunction in Wistar rats. However, PCP and ethanol do have overlapping mechanisms of action and these drugs differentially affect mesolimbic dopaminergic transmission depending on the order of administration. PMID- 20589093 TI - Using coherence to measure regional homogeneity of resting-state FMRI signal. AB - In this study, we applied coherence to voxel-wise measurement of regional homogeneity of resting-state functional magnetic resonance imaging (RS-fMRI) signal. We compared the current method, regional homogeneity based on coherence (Cohe-ReHo), with previously proposed method, ReHo based on Kendall's coefficient of concordance (KCC-ReHo), in terms of correlation and paired t-test in a large sample of healthy participants. We found the two measurements differed mainly in some brain regions where physiological noise is dominant. We also compared the sensitivity of these methods in detecting difference between resting-state conditions [eyes open (EO) vs. eyes closed (EC)] and in detecting abnormal local synchronization between two groups [attention deficit hyperactivity disorder (ADHD) patients vs. normal controls]. Our results indicated that Cohe-ReHo is more sensitive than KCC-ReHo to the difference between two conditions (EO vs. EC) as well as that between ADHD and normal controls. These preliminary results suggest that Cohe-ReHo is superior to KCC-ReHo. A possible reason is that coherence is not susceptible to random noise induced by phase delay among the time courses to be measured. However, further investigation is still needed to elucidate the sensitivity and specificity of these methods. PMID- 20589094 TI - New Perspectives on the Dialogue between Brains and Machines. AB - Brain-machine interfaces (BMIs) are mostly investigated as a means to provide paralyzed people with new communication channels with the external world. However, the communication between brain and artificial devices also offers a unique opportunity to study the dynamical properties of neural systems. This review focuses on bidirectional interfaces, which operate in two ways by translating neural signals into input commands for the device and the output of the device into neural stimuli. We discuss how bidirectional BMIs help investigating neural information processing and how neural dynamics may participate in the control of external devices. In this respect, a bidirectional BMI can be regarded as a fancy combination of neural recording and stimulation apparatus, connected via an artificial body. The artificial body can be designed in virtually infinite ways in order to observe different aspects of neural dynamics and to approximate desired control policies. PMID- 20589095 TI - What roles do tonic inhibition and disinhibition play in the control of motor programs? AB - Animals show periods of quiescence interspersed with periods of motor activity. In a number of invertebrate and vertebrate systems, quiescence is achieved by active suppression of motor behavior is due to tonic inhibition induced by sensory input or changes in internal state. Removal of this inhibition (disinhibition) has the converse effect tending to increase the level of motor activity. We show that tonic inhibition and disinhibition can have a variety of roles. It can simply switch off specific unwanted motor behaviors, or modulate the occurrence of a motor response, a type of 'threshold' controlling function, or be involved in the selection of a particular motor program by inhibiting 'competing' motor mechanisms that would otherwise interfere with the carrying out of a desired movement. A suggested general function for tonic inhibition is to prevent unnecessary non-goal directed motor activity that would be energetically expensive. The reason why basic motor programs might be a particular target for tonic inhibition is that many of them involve central pattern generator circuits that are often spontaneously active and need to be actively suppressed for energy saving. Based on this hypothesis, tonic inhibition represents the default state for energy saving and motor programs are switched-on when required by removal of this inhibition. PMID- 20589096 TI - Confocal Analysis of Cholinergic and Dopaminergic Inputs onto Pyramidal Cells in the Prefrontal Cortex of Rodents. AB - Cholinergic and dopaminergic projections to the rat medial prefrontal cortex (mPFC) are both involved in cognitive functions including attention. These neuronal systems modulate mPFC neuronal activity mainly through diffuse transmission. In order to better understand the anatomical level of influence of these systems, confocal microscopy with triple-fluorescent immunolabeling was used in three subregions of the mPFC of rats and Drd1a-tdTomato/Drd2-EGFP transgenic mice. The zone of interaction was defined as a reciprocal microproximity between dopaminergic and cholinergic axonal segments as well as pyramidal neurons. The density of varicosities, along these segments was considered as a possible activity-dependant morphological feature. The percentage of cholinergic and dopaminergic fibers in microproximity ranged from 12 to 40% depending on the layer and mPFC subregion. The cholinergic system appeared to have more influence on dopaminergic fibers since a larger proportion of the dopaminergic fibers were within microproximity to cholinergic fibers. The density of both cholinergic and dopaminergic varicosities was significantly elevated within microproximities. The main results indicate that the cholinergic and dopaminergic systems converge on pyramidal cells in mPFC particularly in the layer V. In transgenic mice 93% of the pyramidal cells expressed the transgenic marker for Drd2 expression, but only 22% expressed the maker for Drd1ar expression. Data presented here suggest that the modulation of mPFC by dopaminergic fibers would be mostly inhibitory and localized at the output level whereas the cholinergic modulation would be exerted at the input and output level both through direct interaction with pyramidal cells and dopaminergic fibers. PMID- 20589097 TI - Five points on columns. AB - "Column," like "gene," has both conceptual and linguistic shortcomings. The simple question "what is a column" is not easy to answer and the word itself is not easy to replace. In the present article, I have selected five points, in no way comprehensive or canonical, but which may nevertheless serve as a prompt and aid for further discussions and re-evaluation. These are: that anatomical columns are not solid structures, that they are part of locally interdigitating systems, that any delimited column also participates in a widely distributed network, that columns are not an obligatory cortical feature, and that columns (as "modules") occur widely in the brain in non-cortical structures. I focus on the larger scale macrocolumns, mainly from an anatomical perspective. My position is that cortical organization is inherently dynamic and likely to incorporate multiple processing styles. One can speculate that the distributed mappings within areas like piriform cortex may resemble at least one mode of neocortical processing strategy. PMID- 20589098 TI - Different corticostriatal integration in spiny projection neurons from direct and indirect pathways. AB - The striatum is the principal input structure of the basal ganglia. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs) and interneurons. Also: glutamatergic afferents to the striatum come from the thalamus. Despite differences in axonal projections, dopamine (DA) receptors expression and differences in excitability between MSNs from "direct" and "indirect" basal ganglia pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with bacterial artificial chromosome (BAC) transgenic mice, here it is shown that corticostriatal responses in D(1)- and D(2)-receptor expressing MSNs (D(1)- and D(2)-MSNs) are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P > 0.9), in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin (ENK) immunoreactive. Responses are more prolonged and evoke more action potentials in D(1)-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D(2)-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response. Inhibition always depressed corticostriatal depolarization in D(2)-MSNs, while it helped in sustaining prolonged depolarizations in D(1)-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA depletion in 6-hydroxy-dopamine (6-OHDA) lesioned animals: a response reduction was seen in substance P (SP)+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion. PMID- 20589099 TI - Graph-based network analysis of resting-state functional MRI. AB - In the past decade, resting-state functional MRI (R-fMRI) measures of brain activity have attracted considerable attention. Based on changes in the blood oxygen level-dependent signal, R-fMRI offers a novel way to assess the brain's spontaneous or intrinsic (i.e., task-free) activity with both high spatial and temporal resolutions. The properties of both the intra- and inter-regional connectivity of resting-state brain activity have been well documented, promoting our understanding of the brain as a complex network. Specifically, the topological organization of brain networks has been recently studied with graph theory. In this review, we will summarize the recent advances in graph-based brain network analyses of R-fMRI signals, both in typical and atypical populations. Application of these approaches to R-fMRI data has demonstrated non trivial topological properties of functional networks in the human brain. Among these is the knowledge that the brain's intrinsic activity is organized as a small-world, highly efficient network, with significant modularity and highly connected hub regions. These network properties have also been found to change throughout normal development, aging, and in various pathological conditions. The literature reviewed here suggests that graph-based network analyses are capable of uncovering system-level changes associated with different processes in the resting brain, which could provide novel insights into the understanding of the underlying physiological mechanisms of brain function. We also highlight several potential research topics in the future. PMID- 20589100 TI - Drivers and modulators in the central auditory pathways. AB - The classic view of auditory information flow depicts a simple serial route from the periphery through tonotopically-organized nuclei in the brainstem, midbrain and thalamus, ascending eventually to the neocortex. Yet, complicating this picture are numerous parallel ascending and descending pathways, whose roles in auditory processing are poorly defined. To address this ambiguity, we have identified several anatomical and physiological properties that distinguish the auditory glutamatergic pathways into two groups that we have termed "drivers" and "modulators". Driver pathways are associated with information-bearing pathways, while modulator pathways modify these principal information streams. These properties illuminate the potential roles of some previously ill-defined auditory pathways, and may be extended further to categorize either unknown or mischaracterized pathways throughout the auditory system. PMID- 20589101 TI - Functional implications of age differences in motor system connectivity. AB - Older adults show less lateralized task-related brain activity than young adults. One potential mechanism of this increased activation is that age-related degeneration of the corpus callosum (CC) may alter the balance of inhibition between the two hemispheres. To determine whether age differences in interhemispheric connectivity affect functional brain activity in older adults, we used magnetic resonance imaging (MRI) to assess resting functional connectivity and functional activation during a simple motor task. We found that older adults had smaller CC area compared to young adults. Older adults exhibited greater recruitment of ipsilateral primary motor cortex (M1), which was associated with longer reaction times. Additionally, recruitment of ipsilateral M1 in older adults was correlated with reduced resting interhemispheric connectivity and a larger CC. We suggest that reduced interhemispheric connectivity reflects a loss of the ability to inhibit the non-dominant hemisphere during motor task performance for older adults, which has a negative impact on performance. PMID- 20589102 TI - NSAIDs: How they Work and their Prospects as Therapeutics in Alzheimer's Disease. AB - There is significant epidemiological evidence to suggest that there are beneficial effects of treatment with non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease, although these effects have not been reproduced in clinical trials. The failure of the clinical trials may be attributed to several possible facts: (1) NSAIDS may have been delivered too late to patients, as they may only be effective in early stages of the disease and possibly counterproductive in the late stages; (2) the beneficial effect may depend on the drug, because different NSAIDs may have different molecular targets; (3) the NSAID concentration reaching the brain and the duration of the treatment could also be critical, so increasing drug penetration is important in order to improve the efficacy and avoid secondary gastro-intestinal effects of the NSAIDs. In this report we analyze these different factors, with special emphasis on the role of NSAIDs in microglia activation over time. PMID- 20589103 TI - Using network science to evaluate exercise-associated brain changes in older adults. AB - Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise. PMID- 20589105 TI - Transformation twinning of Ni-Mn-Ga characterized with temperature-controlled atomic force microscopy. AB - The magnetomechanical properties of ferromagnetic shape memory alloy Ni-Mn-Ga single crystals depend strongly on the twin microstructure, which can be modified through thermomagnetomechanical training. Atomic force microscopy (AFM) and magnetic force microscopy (MFM) were used to characterize the evolution of twin microstructures during thermomechanical training of a Ni-Mn-Ga single crystal. Experiments were performed in the martensite phase at 25 degrees C and in the austenite phase at 55 degrees C. Two distinct twinning surface reliefs were observed at room temperature. At elevated temperature (55 degrees C), the surface relief of one twinning mode disappeared while the other relief remained unchanged. When cooled back to 25 degrees C, the twin surface relief recovered. The relief persisting at elevated temperature specifies the positions of twin boundaries that were present when the sample was polished prior to surface characterization. AFM and MFM following thermomechanical treatment provide a nondestructive method to identify the crystallographic orientation of each twin and of each twin boundary plane. Temperature dependent AFM and MFM experiments reveal the twinning history thereby establishing the technique as a unique predictive tool for revealing the path of the martensitic and reverse transformations of magnetic shape memory alloys. PMID- 20589104 TI - Age-Related Olfactory Decline is Associated with the BDNF Val66met Polymorphism: Evidence from a Population-Based Study. AB - The present study investigates the effect of the brain-derived neurotrophic factor (BDNF) val66met polymorphism on change in olfactory function in a large scale, longitudinal population-based sample (n = 836). The subjects were tested on a 13 item force-choice odor identification test on two test occasions over a 5 year-interval. Sex, education, health-related factors, and semantic ability were controlled for in the statistical analyses. Results showed an interaction effect of age and BDNF val66met on olfactory change, such that the magnitude of olfactory decline in the older age cohort (70-90 years old at baseline) was larger for the val homozygote carriers than for the met carriers. The older met carriers did not display larger age-related decline in olfactory function compared to the younger group. The BDNF val66met polymorphism did not affect the rate of decline in the younger age cohort (45-65 years). The findings are discussed in the light of the proposed roles of BDNF in neural development and maintenance. PMID- 20589106 TI - Health equity: challenges in low income countries. PMID- 20589107 TI - Is health care financing in Uganda equitable? AB - INTRODUCTION: Health care financing provides the resources and economic incentives for operating health systems and is a key determinant of health system performance. Equitable financing is based on: financial protection, progressive financing and cross-subsidies. This paper describes Uganda's health care financing landscape and documents the key equity issues associated with the current financing mechanisms. METHODS: We extensively reviewed government documents and relevant literature and conducted key informant interviews, with the aim of assessing whether Uganda's health care financing mechanisms exhibited the key principles of fair financing. RESULTS: Uganda's health sector remains significantly under-funded, mainly relying on private sources of financing, especially out-of-pocket spending. At 9.6 % of total government expenditure, public spending on health is far below the Abuja target of 15% that GoU committed to. Prepayments form a small proportion of funding for Uganda's health sector. There is limited cross-subsidisation and high fragmentation within and between health financing mechanisms, mainly due to high reliance on out-of-pocket payments and limited prepayment mechanisms. Without compulsory health insurance and low coverage of private health insurance, Uganda has limited pooling of resources, and hence minimal cross-subsidisation. Although tax revenue is equitable, the remaining financing mechanisms for Uganda are inequitable due to their regressive nature, their lack of financial protection and limited cross subsidisation. CONCLUSION: Overall, Uganda's current health financing is inequitable and fragmented. The government should take explicit action to promote equitable health care financing by establishing pre-payment schemes, enhancing cross-subsidisation mechanisms and through appropriate integration of financing mechanisms. PMID- 20589108 TI - Strategies for sustainability and equity of prepayment health schemes in Uganda. AB - BACKGROUND: Despite the long existence of community health insurance schemes (CHI) in Uganda, their numbers and coverage levels have remained small with limited accessibility by the poor. OBJECTIVES: To examine issues of equity and sustainability in CHI schemes, which are prerequisites to health sector financing. METHODS: We carried out a descriptive cross-sectional study employing qualitative techniques. Eight focus group discussions (FGDs) with CHI scheme members and seven FGDs with non-members were held. Twelve Key informant interviews (KIs) were held with scheme managers, officials from Ministry of Health and one health financing organisation. We reviewed relevant documents and records of schemes. RESULTS: Respondents' perceptions of unfairness in schemes were: non-members were treated better in hospital than members; some members pay premiums continuously without falling sick and schemes refused to cover illnesses like diabetes and hypertension. Fairness was related with the very little payment for the services received, members paying less than non-members but both getting the same treatment and no patient discrimination based on gender, age or social status. Schemes are not sustainable because they operate on small budgets, have low enrolment and lack government support. Effect of abolition of user fees on scheme enrolment was minimal. CONCLUSION: Government should ensure that quality of health care does not deteriorate in the context of increased utilisation after user fees removal, schemes need substantial support to build their sustainability and there is need for technical and policy considerations about whether or not CHI has a role to play in Ugandan health system. PMID- 20589110 TI - Perceptions about human rights, sexual and reproductive health services by internally displaced persons in northern Uganda. AB - BACKGROUND: About 1.6 million internally displaced persons (IDPs) from northern Uganda have been living in encampments since the late 1980s. In conflict settings such as northern Uganda women are disproportionately affected compared to men. This study explores women and men IDPs' perceptions of their access to information about rights, access to health services and gender-based violence. METHODS: This was a cross-sectional study conducted in Kitgum and Pader districts, northern Uganda. We interviewed a total of 1,383 respondents comprising 968 (70%) adults and 415 (30%) adolescents; 60% were females and 40% males, randomly selected from 35 of 67 (52.2%) IDP camps. We held 27 key informant interviews and 52 focus group discussions. Data were entered in EPI data version 3.02 and analysed using SPSS version 12.00 statistical packages. RESULTS: Most (67.5%) of the respondents (68.9% males and 66.6% females) have heard about the notion of human rights. The main sources of information were UN/NGOs 23.7% and radios 23.0%. The right to health (18.8%), freedom of association (16.8%) and the right to education (15.7%) were most known. Although most respondents, 87.3% (88.9% males compared to 85.6% females mentioned preference for delivery in a health unit, main constraints to women's access to health care include lack of money 34.9% males and 37.9% females; lack of information 25.3% males and 23.2% females; and lack of decision power 17.7% males and 17.3% females. Most people (72.7%) (Women: 77.3%; men: 68.5%) perceive gender based violence (GBV) as common in the settings. The main GBV management interventions include treatment of physical injuries 33.9%; testing and treatment for sexually transmitted infections 22.4% and counselling 18.9%. CONCLUSIONS AND RECOMMENDATIONS: Most IDPs are aware about human rights issues mainly through humanitarian agencies and the media. Although geographic accessibility to health services is high, lack of finances, information and decision power hinder women's access to health care services. Duty bearers need to increase community awareness about human rights, both among men and women in order to ensure women's access to health care services. Similarly they must strengthen health systems to provide equitable health services for all IDPs particularly reproductive health services. PMID- 20589109 TI - Will private health insurance schemes subscriptions continue after the introduction of National Health Insurance in Uganda? AB - INTRODUCTION: Uganda is currently designing a National Health Insurance (NHI) scheme, with the aim of raising additional resources for the health sector. Very little was known about the health insurance market in Uganda before this study, so one of our main objectives was to investigate the nature of the private health insurance market in Uganda and the opinions of various stakeholders on NHI, with the view to establish the impact of NHI implementation on the existing PHI. Specifically, we aimed to gather the opinions of employees and employers on the likely impact of NHI on their PHI schemes. METHODS: We conducted interviews with health insurance providers, and a sample of employers and employees in Kampala, using structured questionnaires and analysed quantitative data using STATA. Qualitative data was analysed through grouping of emerging themes. Community based health insurances were excluded from the study. RESULTS: Health insurance and/or prepayment schemes are offered by a handful of organisations or private health providers, mainly in Kampala and cover a relatively small percentage of Uganda's population. The premiums charged and the benefit packages offered by the different agencies vary widely. There are 2 health insurance agencies, 2 HMOs and about 5 or more private providers offering pre-payment schemes to their patients. Responses from a significant proportion of employers and employees show that PHI schemes may be abandoned once the mandatory NHI scheme is implemented. A few respondents argued that they would maintain their PHI subscriptions because of their perceptions of the quality of services likely to be provided under the NHI scheme. CONCLUSION: If successfully introduced, the NHI scheme may displace existing private health insurance and/or pre-payment schemes in Uganda. The extent to which PHI schemes are displaced depends on whether NHI is successfully implemented and the quality of services being offered under the NHI scheme. PMID- 20589111 TI - Funding the promise: monitoring Uganda's health sector financing from an HIV/AIDS perspective. AB - BACKGROUND: HIV/AIDS prevalence in Uganda is beginning to show an upward trend despite increased inflow of funds to fight HIV/AIDS in Uganda. OBJECTIVES: To monitor health sector financing from an HIV/AIDS perspective so as to produce recommendations for effective health service delivery mechanisms in Uganda METHODS: We reviewed the literature and conducted key interviews with service users, policy makers and HIV/AIDS program managers at national and local government levels. Thematic and content analysis guided the presentation of results. RESULTS: While efforts have been put in place to meet its national minimum health care package, much of the support in HIV/AIDS is from donors and NGOs. There is still no clear harmonisation of funding mechanisms and big short fall in health sector budgeting especially at local government level. At this rate Uganda may not achieve its targets CONCLUSION: HIV/AIDS funding in Uganda is largely dependant on donors. There is need for increased and sustained financing from the government if the impact of HIVAIDS is to be reduced. PMID- 20589112 TI - Financial risks associated with healthcare consumption in Jinja, Uganda. AB - INTRODUCTION: Financial access to promotive, preventive, curative and rehabilitative healthcare by every one remains a challenge globally. The requirement to make direct payments at the time of consuming health services is one of the reasons why it persists. In this paper, we present findings on the financial risks households bear as a result of healthcare consumption in one district in Uganda. METHODOLOGY: Using simple random sampling, we selected 384 household heads in 3 health sub districts. A structured questionnaire was to conduct the survey. Focus group discussions and Key Informant interviews were also conducted. RESULTS: Up to 77% (297/384) of households reported making direct payments for healthcare when a household member fell ill, 45% (174/384) did so each time a household member fell ill. Payment for healthcare was associated with employment of the household head in the informal sector (OR 1.6, 95% 1.2-2.1), presence of children OR 1.5, 95% 1.3-1.9 or someone with chronic illness OR 3, 95% 1.5-6 respectively and history of hospitalization (OR 3, 95% 1.7-6.5). CONCLUSION: A high burden of healthcare needs, disproportionately affect children and women among households in Jinja. Direct payments for healthcare still occur in spite of the abolishment of user fees at public health facilities and tax based financing of health services in Uganda. PMID- 20589113 TI - Delivering on a gendered definition of health needs in local government budgeting: experiences and concepts. AB - BACKGROUND: Local governments are granted budgetary power in the Local Governments Act of the Republic of Uganda, which allows for local-level participation and flexibility in the allocation of financial grants channelled annually from central to local governments. The act prescribes a legal mandate to allocate public resources based on local priorities including the health needs of women compared with men. This study investigated the responsiveness of local government budgeting to the health needs of women as compared to men. METHODOLOGY: A qualitative study was conducted in Mpigi district using a set of data collection methods including: a) three (3) focus group discussions with 8 female and 8 male respondents in each group; b) face-to-face interviews with a random sample of 120 households, 75% of which were male-headed and 25% female headed ; c) key informant interviews with a sample of 10 administrative officers in Mpigi district ; and d) desk-review of the Mpigi district Budget Framework Paper. RESULTS: Health needs consist of the daily requirements, which, arise out of common disease infections and the socioeconomic constraints that affect the well-being of women and men. However, the primary concern of the district health sector is disease control measures, without emphasis on the differing socio economic interests of women as compared to men. Local government budgeting, therefore, does not reflect the broad community-wide understanding of health needs. CONCLUSION: Local government budgeting should be informed by a two-fold framework for the gendered definition of health needs. The two-fold framework combines both disease-based health needs and socio-economic needs of women as compared to men. PMID- 20589114 TI - CyberKnife: A new paradigm in radiotherapy. PMID- 20589115 TI - Analytical correction of an extension of the "MU Fraction Approximation" for Varian enhanced dynamic wedges. AB - The most common method to determine enhanced dynamic wedge factors begins with the use of segmented treatment tables. These segmental dose delivery values set as a function of upper jaw position are the backbone of a calculation process coined the "MU Fraction Approximation." Analytical and theoretical attempts have been made to extend and alter the mathematics for this approximation for greater accuracy. A set of linear equations in the form of a matrix are introduced here which correct one published extension of the MU Fraction Approximation as it applies to both symmetric and asymmetric photon fields. The matrix results are compared to data collected from a commissioned Varian Eclipse Treatment Planning System and previously published research for Varian linear accelerators. A total enhanced dynamic wedge factor with excellent accuracy was achieved in comparison to the most accurate previous research found. The deviation seen here is only 0.4% and 1.0% for symmetric and asymmetric fields respectively, for both 6MV and 18MV photon beams. PMID- 20589116 TI - Dosimetry of interface region near closed air cavities for Co-60, 6 MV and 15 MV photon beams using Monte Carlo simulations. AB - Underdosing of treatment targets can occur in radiation therapy due to electronic disequilibrium around air-tissue interfaces when tumors are situated near natural air cavities. These effects have been shown to increase with the beam energy and decrease with the field size. Intensity modulated radiation therapy (IMRT) and tomotherapy techniques employ combinations of multiple small radiation beamlets of varying intensities to deliver highly conformal radiation therapy. The use of small beamlets in these techniques may therefore result in underdosing of treatment target in the air-tissue interfaces region surrounding an air cavity. This work was undertaken to investigate dose reductions near the air-water interfaces of 1x1x1 and 3x3x3 cm(3) air cavities, typically encountered in the treatment of head and neck cancer utilizing radiation therapy techniques such as IMRT and tomotherapy using small fields of Co-60, 6 MV and 15 MV photons. Additional investigations were performed for larger photon field sizes encompassing the entire air-cavity, such as encountered in conventional three dimensional conformal radiation therapy (3DCRT) techniques. The EGSnrc/DOSXYZnrc Monte Carlo code was used to calculate the dose reductions (in water) in air water interface region for single, parallel opposed and four field irradiations with 2x2 cm(2) (beamlet), 10x2 cm(2) (fan beam), 5x5 and 7x7 cm(2) field sizes. The magnitude of dose reduction in water near air-water interface increases with photon energy; decreases with distance from the interface as well as decreases as the number of beams are increased. No dose reductions were observed for large field sizes encompassing the air cavities. The results demonstrate that Co-60 beams may provide significantly smaller interface dose reductions than 6 MV and 15 MV irradiations for small field irradiations such as used in IMRT and tomotherapy. PMID- 20589117 TI - Dose distribution near thin titanium plate for skull fixation irradiated by a 4 MV photon beam. AB - To investigate the effects of scattered radiation when a thin titanium plate (thickness, 0.05 cm) used for skull fixation in cerebral nerve surgery is irradiated by a 4-MV photon beam. We investigated the dose distribution of radiation inside a phantom that simulates a human head fitted with a thin titanium plate used for post-surgery skull fixation and compared the distribution data measured using detectors, obtained by Monte Carlo (MC) simulations, and calculated using a radiation treatment planning system (TPS). Simulations were shown to accurately represent measured values. The effects of scattered radiation produced by high-Z materials such as titanium are not sufficiently considered currently in TPS dose calculations. Our comparisons show that the dose distribution is affected by scattered radiation around a thin high-Z material. The depth dose is measured and calculated along the central beam axis inside a water phantom with thin titanium plates at various depths. The maximum relative differences between simulation and TPS results on the entrance and exit sides of the plate were 23.1% and - 12.7%, respectively. However, the depth doses do not change in regions deeper than the plate in water. Although titanium is a high-Z material, if the titanium plate used for skull fixation in cerebral nerve surgery is thin, there is a slight change in the dose distribution in regions away from the plate. In addition, we investigated the effects of variation of photon energies, sizes of radiation field and thickness of the plate. When the target to be irradiated is far from the thin titanium plate, the dose differs little from what it would be in the absence of a plate, though the dose escalation existed in front of the metal plate. PMID- 20589118 TI - Suitability of point kernel dose calculation techniques in brachytherapy treatment planning. AB - Brachytherapy treatment planning system (TPS) is necessary to estimate the dose to target volume and organ at risk (OAR). TPS is always recommended to account for the effect of tissue, applicator and shielding material heterogeneities exist in applicators. However, most brachytherapy TPS software packages estimate the absorbed dose at a point, taking care of only the contributions of individual sources and the source distribution, neglecting the dose perturbations arising from the applicator design and construction. There are some degrees of uncertainties in dose rate estimations under realistic clinical conditions. In this regard, an attempt is made to explore the suitability of point kernels for brachytherapy dose rate calculations and develop new interactive brachytherapy package, named as BrachyTPS, to suit the clinical conditions. BrachyTPS is an interactive point kernel code package developed to perform independent dose rate calculations by taking into account the effect of these heterogeneities, using two regions build up factors, proposed by Kalos. The primary aim of this study is to validate the developed point kernel code package integrated with treatment planning computational systems against the Monte Carlo (MC) results. In the present work, three brachytherapy applicators commonly used in the treatment of uterine cervical carcinoma, namely (i) Board of Radiation Isotope and Technology (BRIT) low dose rate (LDR) applicator and (ii) Fletcher Green type LDR applicator (iii) Fletcher Williamson high dose rate (HDR) applicator, are studied to test the accuracy of the software. Dose rates computed using the developed code are compared with the relevant results of the MC simulations. Further, attempts are also made to study the dose rate distribution around the commercially available shielded vaginal applicator set (Nucletron). The percentage deviations of BrachyTPS computed dose rate values from the MC results are observed to be within plus/minus 5.5% for BRIT LDR applicator, found to vary from 2.6 to 5.1% for Fletcher green type LDR applicator and are up to -4.7% for Fletcher-Williamson HDR applicator. The isodose distribution plots also show good agreements with the results of previous literatures. The isodose distributions around the shielded vaginal cylinder computed using BrachyTPS code show better agreement (less than two per cent deviation) with MC results in the unshielded region compared to shielded region, where the deviations are observed up to five per cent. The present study implies that the accurate and fast validation of complicated treatment planning calculations is possible with the point kernel code package. PMID- 20589119 TI - Long term response stability of a well-type ionization chamber used in calibration of high dose rate brachytherapy sources. AB - Well-type ionization chamber is often used to measure strength of brachytherapy sources. This study aims to check long term response stability of High Dose Rate (HDR)-1000 Plus well-type ionization chamber in terms of reference air kerma rate (RAKR) of a reference (137)Cs brachytherapy source and recommend an optimum frequency of recalibration. An HDR-1000 Plus well-type ionization chamber, a reference (137)Cs brachytherapy source (CDCSJ5), and a MAX-4000 electrometer were used in this study. The HDR-1000 Plus well-type chamber was calibrated in terms of reference air kerma rate by the Standards Laboratory of the International Atomic Energy Agency (IAEA), Vienna. The response of the chamber was verified at regular intervals over a period of eight years using the reference (137)Cs source. All required correction factors were applied in the calculation of the RAKR of the (137)Cs source. This study reveals that the response of the HDR-1000 Plus well-type chamber was well within +/-0.5% for about three years after calibration/recalibration. However, it shows deviations larger than +/-0.5% after three years of calibration/recalibration and the maximum variation in response of the chamber during an eight year period was 1.71%. The optimum frequency of recalibration of a high dose rate well-type chamber should be three years. PMID- 20589120 TI - Performance evaluation of an algorithm for fast optimization of beam weights in anatomy-based intensity modulated radiotherapy. AB - This study aims to evaluate the performance of a new algorithm for optimization of beam weights in anatomy-based intensity modulated radiotherapy (IMRT). The algorithm uses a numerical technique called Gaussian-Elimination that derives the optimum beam weights in an exact or non-iterative way. The distinct feature of the algorithm is that it takes only fraction of a second to optimize the beam weights, irrespective of the complexity of the given case. The algorithm has been implemented using MATLAB with a Graphical User Interface (GUI) option for convenient specification of dose constraints and penalties to different structures. We have tested the numerical and clinical capabilities of the proposed algorithm in several patient cases in comparison with KonRad((R)) inverse planning system. The comparative analysis shows that the algorithm can generate anatomy-based IMRT plans with about 50% reduction in number of MUs and 60% reduction in number of apertures, while producing dose distribution comparable to that of beamlet-based IMRT plans. Hence, it is clearly evident from the study that the proposed algorithm can be effectively used for clinical applications. PMID- 20589121 TI - Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer. AB - Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage. PMID- 20589122 TI - Applying graphics processor units to Monte Carlo dose calculation in radiation therapy. AB - We investigate the potential in using of using a graphics processor unit (GPU) for Monte-Carlo (MC)-based radiation dose calculations. The percent depth dose (PDD) of photons in a medium with known absorption and scattering coefficients is computed using a MC simulation running on both a standard CPU and a GPU. We demonstrate that the GPU's capability for massive parallel processing provides a significant acceleration in the MC calculation, and offers a significant advantage for distributed stochastic simulations on a single computer. Harnessing this potential of GPUs will help in the early adoption of MC for routine planning in a clinical environment. PMID- 20589123 TI - Measurement of time delay for a prospectively gated CT simulator. AB - For the management of mobile tumors, respiratory gating is the ideal option, both during imaging and during therapy. The major advantage of respiratory gating during imaging is that it is possible to create a single artifact-free CT data set during a selected phase of the patient's breathing cycle. The purpose of the present work is to present a simple technique to measure the time delay during acquisition of a prospectively gated CT. The time delay of a Philips Brilliance BigBore (Philips Medical Systems, Madison, WI) scanner attached to a Varian Real Time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA) was measured. Two methods were used to measure the CT time delay: using a motion phantom and using a recorded data file from the RPM system. In the first technique, a rotating wheel phantom was altered by placing two plastic balls on its axis and rim, respectively. For a desired gate, the relative positions of the balls were measured from the acquired CT data and converted into corresponding phases. Phase difference was calculated between the measured phases and the desired phases. Using period of motion, the phase difference was converted into time delay. The Varian RPM system provides an external breathing signal; it also records transistor-transistor logic (TTL) 'X-Ray ON' status signal from the CT scanner in a text file. The TTL 'X-Ray ON' indicates the start of CT image acquisition. Thus, knowledge of the start time of CT acquisition, combined with the real-time phase and amplitude data from the external respiratory signal, provides time-stamping of all images in an axial CT scan. The TTL signal with time-stamp was used to calculate when (during the breathing cycle) a slice was recorded. Using the two approaches, the time delay between the prospective gating signal and CT simulator has been determined to be 367 +/- 40 ms. The delay requires corrections both at image acquisition and while setting gates for the treatment delivery; otherwise the simulation and treatment may not be correlated with the patient's breathing. PMID- 20589125 TI - Multiplicity of Plasmodium falciparum infection predicts antimalarial treatment outcome in Ugandan children. AB - BACKGROUND: In areas with intense malaria transmission, individuals are often simultaneously infected with multiple parasite strains. This study assessed the effect of multiple infections on treatment response in Ugandan children with uncomplicated malaria. METHODS: Four hundred and seventy six blood specimens were analysed for parasite genetic diversity. The P.falciparum merozoite surface protein-2 (msp-2) was analysed to establish multiplicity of infection for pre and post treatment specimens. RESULTS: There were 32 different msp-2 alleles, 15 corresponding to the IC/3D7 and 17 to the FC27 allelic family. The majority of the isolates (343, 72 %) were multiple infections resulting into an overall mean multiplicity of infection of 2.15 (SD+/-1.02). Children infected with multiple strains had nearly a 3-fold increase in treatment failure (Hazard Ratio = 2.8, 95 % CI: 1.5-5.3) compared to their age mates infected with a single strain. CONCLUSION: Multiple-strain infection reduced response to antimalarial therapy. Strategies that reduce multiple-strain infections (intermitted presumptive treatment, indoor residual spraying, insecticide treated nets and efficacious drugs) are likely to improve antimalarial drug efficacy and reduce rate of spread of drug resistance. PMID- 20589126 TI - Intravascular catheter related infections in children admitted on the paediatric wards of Mulago Hospital, Uganda. AB - INTRODUCTION: Worldwide use of intravascular catheters (IVC) has been associated with both local and systemic infections. No studies have been done in the sub Saharan region on IVC related infections. OBJECTIVE: To determine the prevalence, causative organisms and their antimicrobial susceptibility pattern and the factors associated with infections related to short term peripheral venous catheters in children admitted to the general paediatric wards in Mulago Hospital, Uganda. METHODS: A cross-sectional study of 391 children aged one day to 12 years, on Jelliffe ward in Mulago Hospital, who had short peripheral venous intravascular catheters uncoated with no antibiotic or antiseptic, was done. Social demographic characteristics, anthropometry, clinical examination including the catheter site were determined at enrollment. The children had their blood, catheter tip and hub samples taken off for culture and sensitivity as well as complete blood counts. The data collected was entered using EPI-INFO and analysed with SPSS packages. RESULTS: Out of the 391 short term peripheral venous catheters collected, 20.7% catheter tips and 11.3% catheter hubs were colonised. Phlebitis was observed in 17.4%. Bacteria isolated from colonised catheter tips were Staphylococcus aureus (60.5%), Staphylococcus epidermidis (23.5%). The most common organism isolated from the hub was Staphylococcus aureus (56.8%) followed by Staphylococcus epidermidis (18.1%). Gram positive and negative organisms were sensitive to ciprofloxacin, gentamycin for gram-negative organisms and augmentin, cefuroxime, ceftriaxone for the gram-positive organisms. After logistic regression, factors such oedema, modified Glasgow coma score of <10/15, 6 hourly benzyl penicillin were significantly associated with colonisation of the tip while use of 25% dextrose, chloramphenicol 6 hourly and blood transfusion were significantly associated with colonisation of the hub. CONCLUSION: The study showed that infections related to short peripheral venous catheters in paediatric general wards in Mulago Hospital occurs and prevalence was 20.72% for tips and 11.3% for hubs. PMID- 20589127 TI - Haemorheologic and fibrinolytic activity in Nigerian HIV infected patients. AB - OBJECTIVE: Human immunodeficiency virus (HIV)-infected patients, especially those on antiretrovirals are at risk of cardiovascular disease (CVD). The haemorheologic and fibrinolgtic activity of treatment naive Nigerian HIV-infected patients were investigated. METHODS: Blood was collected from 50 newly diagnosed treatment naive HIV-infected patients and 50 apparently healthy HIV seronegative individuals that served as controls. Haematocrit values, plasma and serum viscosity, plasma fibrinogen concentration and euglobin lysis time were determined. RESULT: The mean +/- standard deviation of haematocrit value of HIV infected patients (31.70 +/- 6.33%) was significantly lower (p<0.0001) than those of controls (39.50 +/- 2.43%). The plasma serum viscosity, plasma fibrinogen concentration and euglobin lysis time of HIV-infected patients were significantly higher compared with those of controls (p<0.0001). CONCLUSION: Treatment naive Nigerian HIV-infected patients have a defective blood flow and fibrinolytic system, which may predispose them to CVD. PMID- 20589128 TI - Access and use of medicines information sources by physicians in public hospitals in Uganda: a cross-sectional survey. AB - BACKGROUND: Rational and cost-effective prescription of medicines requires up-to date and readily accessible medicines information. There are several studies on availability and access to medicines information sources, but have been conducted only in high-income countries. OBJECTIVE: To assess medicines information sources accessed by physicians in public hospitals in Uganda, and physicians' opinion on establishment of a medicines information centre in the country. METHODS: A cross sectional survey including 369 physicians from six district, six regional and two university hospitals. Data was collected using a semi-structured self administered questionnaire. RESULTS: Response rate was 91%. This included 31, 136 and 168 physicians from the district, regional and university hospitals, respectively. In the district hospitals the source of medicines information reported to be most available was colleagues (100%), while in the regional and university hospitals it was literature from pharmaceutical companies (98%) and hard copy of research publications (99%) respectively. The most frequently used source in the district and regional hospitals was National Standard Treatment Guideline (90% and 73% respectively), and colleagues in university hospitals (89%). Accessibility problems with reported available sources were commonest with research publications in medical journals, both hard copy and through the internet, MIMS, pharmacists and pharmacologists. Need for a medicines information centre was indicated by 80% of the respondents. CONCLUSION: Majority of the physicians in public hospitals in Uganda have limited access to unbiased drug information. Therefore, there is need to assess the feasibility of establishing a drug information centre, and then assess its use during a trial period. PMID- 20589129 TI - Youth of West Cameroon are at high risk of developing IDD due to low dietary iodine and high dietary thiocyanate. AB - OBJECTIVES: Hypothyroidism in utero leading to mental retardation is highly prevalent and recurrent in developing countries where iodine deficiency and thiocyanate overload are combined. So, to explore and identify human population's risks for developing iodine deficiency disorders and their endemicity in Western Cameroon, with the aim to prevent this deficiency and to fight again it, urinary iodine and thiocyanate levels were determined. METHODS: The district of Bamougoum in Western Cameroon was selected for closer study due to its geographic location predisposing for iodine deficiency disorders (IDD). A comprehensive sampling strategy included 24-h urine samples collected over three days from 120 school aged children. Urinary iodine and thiocyanate levels were measured by colorimetric methods. RESULTS: Twenty one percent of boys between the ages 3 and 19 were classified as iodine deficient. The prevalence of thiocyanate overload in the same population was found to be 20%. CONCLUSION: Presence of endemic iodine deficiency and excessive thiocyanate in the population indicates that the region is at risk of iodine deficiency disorder. A multifactorial approach that includes improvement of diet, increasing iodine and minimizing goitrogen substances intake, soil and crop improvement and an iodine supplementation program may help alleviate IDD in the affected area studied. PMID- 20589130 TI - p53 expression in colorectal carcinoma in relation to histopathological features in Ugandan patients. AB - BACKGROUND: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular pathogenesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been associated with poor clinical outcome and reduced survival in patients. OBJECTIVE: This was a retrospective laboratory based study carried out in the Department of Pathology Makerere University, Kampala, Uganda. The aim of the study was to evaluate the expression of p53 protein in colorectal carcinoma in Ugandan patients, specifically its association with histological types, degree of differentiation, sites of the tumor and demographic characteristics of the patients. METHODS: Immunohistochemistry was carried out on 109 patient's paraffin embedded tissue blocks of colorectal carcinoma diagnosed in the Pathology Department, Faculty of Medicine Makerere University Kampala during the period 1995 to 2005. The indirect immunoperoxidase method using monoclonal antibody p53 DO-7 and Envision (+) Dual link system-HRP to detect p53 expression was used. Haematoxylin and eosin stain was used for evaluation of histological types and degree of differentiation of the tumors. Topography of the tumors and demographic data were obtained from accompanying histological request forms. RESULTS: Out of 109 patient's tissue blocks that were studied, 61 cases (56%) expressed p53 protein in the nucleus of malignant cells. Right sided colonic tumors were commoner (53.2%) than left sided colonic tumors (46.8%). p53 protein was expressed more in left sided colonic tumors with a significant difference (p<0.05), it was also expressed more in well differentiated tumors and non mucinous adenocarcinomas but with no significant difference (p>0.05). p53 expression was not affected by age or sex. CONCLUSION: Frequency of p53 protein expression in Ugandan patients did not differ from that reported in the other parts of the world. It was expressed more in the left sided colonic tumors and this could support the hypothesis that right and left colonic tumors could have different pathogenesis and probably also responsible for difference in prognosis in these two topographic sites. PMID- 20589131 TI - Epidemiology, of bilharzias (schistosomiasis) in Uganda from 1902 until 2005. AB - BACKGROUND: Schistosoma mansoni was observed and reported in Kuluva hospital Arua District in north western Uganda as early as 1902. S. mansoni is widely distributed in Uganda along permanent water bodies. OBJECTIVE: To review the litreture on scistosomiasis in Uganda, since 1902. METHOD: The core literature for this short review was searched from reports and publications by the British colonial Ministry of Health Districts Medical officers and Entomologists. Additional information was obtained from Makerere University Medical School library archives, London School of Hygiene and Tropical Medicine library archives, University of Antrwap, and post independence publications on schistosomiasis in Uganda in various journals. RESULTS: Since it was first detected in 1902 Schistosoma (S) mansoni is more widely distributed in Uganda than S. haematobium. However Schistosoma mansoni and S. haematobium are of public health importance in Uganda and the importance of migrants and fishermen in disseminating infections into non-infested areas and intensifying infection in areas already infested have been reported. CONCLUSION: S. mansoni has been on the increase in Uganda whereas S. haematobium is localized in sporadic foci in the north of Uganda. Treatment with praziquantel the drug of choice in Uganda used in schistosomiasis control programme has reduced development of severe schistosomiasis. PMID- 20589132 TI - Factors associated with malnutrition among children in internally displaced person's camps, northern Uganda. AB - INTRODUCTION: Since mid 1990s, Uganda has had an estimated 1.6 million internally displaced persons (IDPs) in the northern and eastern districts. A major cause of morbidity and mortality amongst children in displaced settings is protein energy malnutrition. OBJECTIVE: To estimate the prevalence of and describe the risk factors for protein energy malnutrition among under five years old children living in internally displaced persons camps in Omoro county Gulu district. METHODS: This was a cross sectional study undertaken among internally displaced people's in Omoro county, Gulu district during 13 - 23(rd) September 2006. Anthropometric measurements of 672 children aged 3 - 59 months were undertaken and all their caretakers interviewed. The anthropometric measurements were analyzed using z-scores of height-for-age (H/A) and weight-for-height (W/H) indices. Qualitative data were collected through 6 focus group discussions, key informant interviews and observation. Data were captured using Epi Data version 3.0 and analyzed using EPI-INFO version 3.3.2 and SPSS version 12.0 computer packages respectively. ResultsThe prevalence of global stunting was found to be 52.4% and of global acute malnutrition 6.0%. Male children are at risk of being stunted Adjusted OR 1.57 95% CI 1.15-2.13; p value=0.004. Children in the age group 3 - 24 months were at risk of acute malnutrition Adjusted OR 2.78 95% CI 1.26-6.15; p value=0.012 while de-worming was protective Adjusted OR 0.44 95% CI 0.22-0.88; p value=0.018. The main sources of foodstuff for IDPs include food rations distributed by WFP, cultivation and purchase. CONCLUSION AND RECOMMENDATIONS: There is high prevalence of protein energy malnutrition (stunting) among children in the internally displaced people's camps in Gulu district. Male children are at an increased risk of stunting while children aged between 3 - 24 months are at an increased risk of suffering from acute malnutrition. Stakeholders including local government and relief organizations should intensify efforts to improve the nutritional status of IDPs especially children in the camp settings. The quantity of and access to household food supplies, health education on infant and child feeding and integrated management of childhood illnesses (IMCI) activities in the camps should be strengthened. PMID- 20589133 TI - Pattern of ptosis in Kano North-West Nigeria. AB - OBJECTIVE: Epidemiological data on ptosis are generally lacking in the developing nations. The aim of this study was to assess the seven years pattern of ptosis in a Nigerian Specialist Hospital, Kano North-West Nigeria. METHOD: The records of patients' diagnosis as ptosis between 2000 and 2006 were scrutinized. Data such as age, sex, cause, socioeconomic status, side of ptosis and management were obtained. RESULT: A total number of 104 patients were recorded. High prevalence was found as follows: male 102(65.4%); right side (61.5%); trauma (RTA) (60.9%); civil servants (38.5.8%) and age group: 51-60 years (25.6%). CONCLUSION: It was concluded that trauma from road traffic accident (RTA) is the major aetiological factor and the right side mostly affected. RECOMMENDATION: It is recommended that surgical training and facilities for ptosis correction is off priority. PMID- 20589134 TI - Coarctation of aorta presenting as acute haemorrhagic stroke in a 14-year old. A case report. PMID- 20589135 TI - Pioneer human open heart surgery using cardiopulmonary by pass in Uganda. AB - INTRODUCTION: For the first time in Uganda in April 2007,two open-heart surgeries were done using cardiopulmonary by pass. A multidisciplinary team of largely indigenous Ugandans professionals working in Uganda formed the pioneering team. CONTEXT: Access in cardiac surgery in the developing countries is very limited. The challenges that impede access to adequate and appropriate health care including open-heart surgery are in the least complex and daunting. PATIENT SELECTION: Two 13 and 17 year old males with Secundum Atrial Septal defects were chosen from a long waiting list. The criteria used included no or minimal co morbidity states, patient fitness and available ICU ventilation facilities. PREPARATION: Took an eleven months period, including formulation and adoption of peri and intra operation protocols, training of staff, sourcing of usable and mobilizing the financing. OUTCOMES: The procedure for the two patients was successfully performed. The immediate and short-term postoperative periods were uneventful. At the twelve months review point both patients were leading a normal life. In the months that followed 19 other open-heart procedures were done including two mitral valves replacements. CONCLUSION: This program has greatly enhanced the level of care for the critically ill at this facility. Its sustenance and replication in other centres in the country is essential. Government and development partners' support is critical. The educational value of this program ought to be exploited by health professions students in the country. PMID- 20589136 TI - Health and social care curricula--future perspectives for learner experience in Europe and Africa. PMID- 20589137 TI - Workshops on healthy lifestyle to adolescents. PMID- 20589139 TI - CD4+ lymphocyte values and trends in individuals infected with human immunodeficiency virus and/or co-infected with hepatitis C virus in the Gambia. AB - OBJECTIVES: This study was undertaken to monitor the CD4+ lymphocyte count in individuals infected with Human Immunodeficiency Virus (HIV) and/or co-infected with Hepatitis C Virus (HCV) and to compare this with the counts in normal individuals in The Gambia. METHODS: Blood samples were taken from 1500 individuals referred for HIV serology at the Royal Victoria Teaching Hospital (RVTH) following informed consent. Samples were tested for antibodies to HIV by the Murex ELISA, antibodies to HCV by the Ortho ELISA, and CD4 counts determined by the Dynalimmunomagnetic cell isolation method RESULTS: Of the 1500 patients screened for HIV and HCV antibodies, 6.7% (101/1500) were infected with HIV, 0.6 % (9/1500) were co-infected with HCV and 1.5 % (22/1500) were infected with HCV alone. Almost half (44.6%; 25/56) of HIV-1 infected patients had a CD4+ lymphocyte count at diagnosis of 200 cells/microl or less as compared to 41.7 % (10/24) of HIV-2 and 75% (6/8) of HIV-D infected patients. The rate of CD4 decline was higher among HIV/HCV co-infected persons than individuals infected with HIV or HCV. The rate of decline was higher among men than women. These differences did not reach statistical significance due in large part to the small number of participants who completed the programme. The CD4+ lymphocyte count of apparently healthy Gambian male and females was 489 cells/microl and 496 cells/microl respectively. This rate is lower than that reported for Caucasians, but in agreement with the global range. CONCLUSION: A significant progressive decline in CD4+ lymphocyte count was observed among the female control group who were negative for HIV and HCV. This finding is unclear and calls for a longitudinal study involving a cohort of women in this region. PMID- 20589140 TI - Rapid screening for co-infection of HIV and HCV in pregnant women in Benin City, Edo State, Nigeria. AB - BACKGROUND: Human Immunodeficiency virus (HIV) and Hepatitis C virus (HCV) are both major global health concerns as they cause high mortality and morbidity in the developing countries. However, while data exists for the co-infection in other countries, little or no information can be found with regard to the sero prevalence of HIV and HCV co-infection in Nigeria, albeit in pregnant women attending antenatal care clinics in Benin City, Nigeria. OBJECTIVE: The objective of the study was to determine the sero-prevalence of HIV and HCV among pregnant women seeking antenatal care in Benin City. METHODS: In determining the sero prevalence in a cross-sectional study, 200 pregnant women, aged between 15 and 49 years were screened for HIV and HCV using rapid screening test kits. Using closed ended structured questionnaires; the respondents volunteered socio-demographic information associated with risk factors of HIV and HCV acquisition. RESULTS: Results indicated sero-prevalence of HIV and HCV in the sampled population was 3% and 5% respectively. Thirty three percent of the pregnant women that were HCV positive were co-infected with HIV-1 infection. HIV sero-prevalence was highest in the age group, 25-29 representing 5.1%, while HCV sero-prevalence was noted highest among the women in the age group 30-34 years, representing 7.9%. Two percent of the pregnant women had equivocal (ambivalent) HIV-1 results. CONCLUSION: The study has shown a prevalence of HIV-HCV co-infection among the tested pregnant women in Benin City and more epidemiological surveys are needed in larger scale to decipher the prevalence in other states of Nigeria. PMID- 20589141 TI - Screening for hepatitis C among HIV positive patients at Mulago hospital in Uganda. AB - BACKGROUND: In industrialized countries with more resources, it is recommended that HIV infected patients should be screened for hepatitis C virus (HCV) on entry into the health care system. Implementation of these guidelines in a country like Uganda with limited resources requires some modification after taking into account the prevailing circumstances. These include the prevalence of HCV in HIV positive patients and the cost of HCV testing. OBJECTIVE: The objective of the study was to estimate the prevalence of HCV in HIV positive patients. METHODS: This was a cross sectional study among HIV positive outpatients in Mulago hospital. HCV screening was done using anti-HCV Enzyme Immuno Assay (Roche Diagnostics) RESULTS: Between October 2003 and February 2004, one hundred and twenty two HIV positive patients were enrolled into the study with a mean age of 33.9 years. There were more females 81 (66.4%) than males. Only 4 patients had anti-HCV, giving an estimated HCV prevalence of 3.3%. CONCLUSION: In view of the low HCV prevalence found in our study and similar studies and considering the high cost of HCV screening, routine HCV testing cannot be recommended among all HIV positive patients in our health care settings with limited resources. We recommend that HCV screening be limited to investigating HIV positive patients with features suggestive of liver disease in order to identify HCV as a possible cause. PMID- 20589142 TI - Predictors of smoking initiation among schoolchildren in Tunisia: a 4 years cohort study. AB - OBJECTIVE: To identify predictors of smoking initiation among non smoking Tunisian school children; and to propose efficient antismoking strategies in order to prevent smoking initiation. METHODS: It was a cohort study surveying prospectively for four years pupils attending schools in Sousse city in Tunisia. 441 non smoking pupils aged 13-15 years attending secondary schools in Sousse. Data were collected by a self administered questionnaire during class session. Two ways cross tabulation, univariate and multivariate logistic regression analyses were the main analytical methods. RESULTS: 57.1% of the surveyed population were girls, 42.9 % were boys. 63% had at least one of their peers who smoked. Before 1999, 16.6% had already tried to smoke, 29.5% had already experienced alcohol. In 2003, smoking prevalence was 17%. 4.8% were girls; 33.3% of boys; p<0,001). 69.9 % of these smokers declared that they would carry on smoking during the following five years. Predictors which were highly associated with smoking initiation were previous experimentation with alcohol and tobacco, having a smoking best friend, lack of sensitization from the part of the school, believing that smoking makes one feel cool and that tobacco shouldn't be forbidden in public places. CONCLUSION: Intervention programs should target young children to avoid experiencing the first cigarette. Multidisciplinary management including community and school based intervention highlighted by mass media campaigns may provide schoolchildren with skills to resist smoking peers prompts to adopt unhealthy habits such as smoking. PMID- 20589143 TI - Prevalence factors associated with hypertension in Rukungiri district, Uganda--a community-based study. AB - BACKGROUND: Hypertension is a growing public health problem in Uganda and Africa as a whole. We conducted a study to determine the prevalence and identify factors associated withy hypertension among residents of the rural district of Rukungiri, Uganda. METHODS: A community-based cross-sectional study design was used to conduct this study. Between January and February 2006, a random sample of consenting district residents, aged 20 years or older were enrolled to participate in this study. Trained research assistants administered a standardized questionnaire and performed the physical measurements. The questionnaire collected data on demographics, social economic and exposure history to various potential risk factors for hypertension. Hypertension was defined as systolic blood pressure (BP) equal or greater than 140mmHg and/or diastolic BP equal or greater than 90mmHg, and/or being on regular anti hypertensive therapy. Logistic regression analysis was used to identify factors associated with hypertension. RESULTS: Of the 842 study participants, 252 were hypertensive. The age-standardized prevalence of hypertension was 30.5%, with a 95% Confidence Interval (CI) of 26.6 - 34.3%. Factors found to be associated with hypertension included: past alcohol use, Odds Ratio (OR)=2.28, [1.42 - 3.64], present alcohol use OR=1.64 [1.12 - 2.43], being overweight OR=1.95 [1.37 - 2.79], obesity OR=5.07 [2.79 - 9.21], female sex OR=1.44 [1.03 - 2.06], having attained tertiary education OR=1.91 [1.03 - 3.56], and older age OR=1.42 [1.27 - 1.59]). CONCLUSION: The prevalence of hypertension in this rural Ugandan district is relatively high. The findings confirm the growing concern about hypertension as a public health problem in Uganda. More studies are however required to determine the distribution and determinants of hypertension in other parts of the country. PMID- 20589144 TI - A comparison of two measures of quality of life of Nigerian clinic patients with type 2 diabetes mellitus. AB - BACKGROUND: We present data comparing the quality of life effects of type 2 diabetes determined by the Bradley well-being questionnaire and the WHOQOL-BREF, a generic instrument. We also present data on the reliability and validity of these instruments. METHOD: The Well-being and the WHO-bref were administered on fifty-three consecutive type 2 diabetics. The internal consistency of the quality of life scales was assessed using Cronbach's alpha. Convergent, discriminant, and known groups validity were determined and compared. RESULTS: Our patients had a mean age of 55.8+/-13 years. 31(58.5%) were males and all patients had been diabetic for 7.9+/-7.1 years. 13(24.5%) were being treated with oral agents, 14(26.4%) were on insulin and 26(49.1%) were on combined therapy. The Cronbach alpha coefficients ranged from 0.31 to 0.72 on the Well-being subscales and from 0.47 to 0.78 on the WHOQOL-BREF subscales. Both scales were modestly related to one another. In general the quality of life measures were not influenced by characteristics such as age, gender, marital or educational status. Both scales were not influenced significantly by treatment type or the severity or number of complications. CONCLUSION: Our study has shown how two different measures of quality of life perform in patients with type 2 diabetes. Even though the subscales of the Well-being and WHOQOL-BREF were not very sensitive to external criteria of disease impact (complications) casting a doubt on their utility as psychological outcome measures, they demonstrated fairly reasonable internal consistency in our patients with type 2 diabetes. Further larger studies are thus required to clarify this given our present limitations. PMID- 20589145 TI - Reactive airway and anaesthesia: challenge to the anaesthetist and the way forward. AB - BACKGROUND: Patients with concurrent medical conditions such as Reactive airway disease presenting for anaesthesia, and surgery have potentially increased risk of perioperative morbidity and mortality if not well managed. OBJECTIVE: To highlight the need for adequate perioperative care and review the evidence for selection of techniques in the anesthesia for such cases" MATERIALS AND METHODS: An illustrative case is presented. CONCLUSION: The main goal of the anaesthetist is to administer safe and sufficient anaestheia without precipitating bronchospasm. PMID- 20589146 TI - Pattern and outcome of childhood intestinal obstruction at a tertiary hospital in Nigeria. AB - BACKGROUND: Intestinal obstruction is a common cause of pediatric surgical emergency with a high morbidity and mortality in Africa. METHODS: A retrospective review of cases managed from January 1996 to December 2005 at a teaching hospital in Southwestern, Nigeria was done to examine the pattern of causes of intestinal obstruction in children and the management outcome. RESULTS: One hundred and thirty cases were seen over the study period with an age range of 2 hours to 14 years. Majority (61.24%) were infants, while 18.46% were neonates. Fifty-five cases (42.31%) were due to congenital causes while the rest were of acquired causes. The major causes of intestinal obstruction in the study were intussusception (29.23%), anorectal malformations (22.31%), obstructed inguinoscrotal hernia (16.92%) and Hirschsprung's disease (13.85%). Surgical site infection and sepsis were the commonest complications observed with an overall complication rate of 60.78%. The mortality rate was 3.08% and most (75%) occurred in neonates. CONCLUSION: While mortality as an outcome of management is low, the morbidity was very high in this study. PMID- 20589147 TI - Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians. AB - BACKGROUND: The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden. METHODS: Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented. OBJECTIVES: To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria. RESULTS: Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin's lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant. CONCLUSION: Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians. PMID- 20589148 TI - A re-appraisal of warfarin control in the treatment of deep vein thrombosis and / or pulmonary embolism. AB - BACKGROUND: Warfarin is commonly used for management of deep vein thrombosis (DVT) and pulmonary embolism (PE), controlling therapy by means of the International Normalized Ratio (INR). OBJECTIVES: To identify differences in INR results between patients with thromboembolic and haemorrhagic complications and controls. METHODS: Two nested case-control studies from within a controlled trial of the duration of warfarin therapy (47 thrombotic and 16 haemorrhagic complications). RESULTS: Patients whose thromboembolism failed to resolve during treatment or recurred during or after treatment had non-significantly lower INR levels than matched controls (geometric mean 2.2 versus 2.3, p = 0.12). Patients with haemorrhage also had not statistically significant lower INR levels than their matched controls (2.1 versus 2.3, p = 0.22). The variability of INR levels was similar in both case groups and controls. The mean percentage of INR levels in the therapeutic range 2 - 3 was almost identical in thrombotic cases and controls (56.5% versus 56.1%). Compared to the haemorrhagic group, better control was achieved in controls (61.5% versus 43.0%, p=0.01), but controls had slightly more INR values above the therapeutic range (12.1% versus 10.5%, p = 0.74) whilst haemorrhagic cases had more INR values below the therapeutic range (46.6% versus 26.4%, p = 0.03). CONCLUSION: In this study, higher INR levels were not associated with haemorrhage suggesting that, for patients being treated for DVT/PE, a modest increase in the target therapeutic range could be considered. PMID- 20589149 TI - A preliminary examination of the construct validity of the KABC-II in Ugandan children with a history of cerebral malaria. AB - BACKGROUND: Several diseases and adverse conditions affect the cognitive development of children in Sub-Saharan African. There is need to assess these children to determine which abilities are affected and the severity of the damage so as to plan interventions accordingly. However most psychological tests developed in the West have not been validated in this region making it impossible to know whether they measure what they were intended to in African children. OBJECTIVE: To examine the construct validity of the Kaufman Assessment Battery for Children, Second Edition (KABC-II) in Ugandan children. METHODS: Sixty five Ugandan children aged 7 to 16 years (Mean=9.90, SD=2.46) were tested using the KABC-II 44.59 months (SD=2.82) after an episode of cerebral malaria. The KABC-II scales of Sequential Processing, Simultaneous Processing, Planning and Learning were administered. In order to identify which factors result from administering the KABC-II in these children, factor analysis using principal component analysis with Varimax rotation was applied to the subtests making up the above scales. RESULTS: Five factors emerged after factor analysis comprising of subtests measuring Sequential Processing, Simultaneous Processing, Planning and Learning. The fifth scale comprised of subtests measuring immediate and delayed recall. CONCLUSION: This preliminary study in Ugandan children shows the KABC-II to have good construct validity with subtests measuring similar abilities loading on the same factor. The KABC-II can be used in assessing Ugandan children after a few modifications. Further analysis of its psychometric properties in Ugandan children is required. PMID- 20589150 TI - Case finding for hypertension in young adult patients attending a missionary hospital in Nigeria. AB - OBJECTIVES: This study was carried out to search for cases of undetected hypertension in young adult male and non-pregnant female patients (18 - 44years) attending a catholic mission hospital in Ibadan, Nigeria so as to provide evidence for routine blood pressure checks in this age group. It also sought to determine risk factors present in those found to be hypertensive and to detect complications of hypertension, if present. METHODS: Semi-structured questionnaire was administered and physical examination was carried out on the eligibles. Laboratory analysis of blood and urine was done for the consenting subjects with confirmed hypertension. A descriptive, hospital-based cross-sectional study, which took place at the Out-Patients Department of St. Mary's Catholic General Hospital, Eleta, Ibadan. Consecutive young adult male and non-pregnant female patients aged 18 - 44 years attending the hospital for the first time between February 2007 and August 2007, that met the inclusion criteria and consented to participation. DATA ANALYSIS: Frequency distribution was done to describe the data, while cross-tabulation, t-test, chi-square test and one-way ANOVA were done to explore association between variables as appropriate. RESULTS: Out of the 405 subjects that participated in the study, 124(30.6%) were hypertensive. The mean age of the subjects was 31.6 +/-6.9 years. A total of 154 (38%) were male and 251(62%) female. Mean BMI was 23.7+/-4.3 kg/m(2). The study revealed that age, occupation, body mass index, waist circumference and hip circumference were significantly associated with high blood pressure. Clinical evidence of target end-organ damage seen include left ventricular hypertrophy in 22(17.7%) congestive cardiac failure in 3(2.4%), retinopathy in 5(4.0%), nephropathy in 12(26.1%) and transient ischaemic attack in 1(0.8%). CONCLUSION: Undetected cases of hypertension, with complications and target end-organ damage, exist in young adults in Ibadan and family physicians and other primary care physicians, especially in Nigeria, should pay attention to case finding for hypertension in this age group. PMID- 20589151 TI - Impact of mouth rinsing before sputum collection on culture contamination. PMID- 20589152 TI - Campylobacter spp among children with acute diarrhea attending Mulago hospital in Kampala--Uganda. AB - BACKGROUND: Campylobacter infections occur worldwide. A recent study in Kampala, Uganda, found that 87% of broiler chickens had Campylobacter jejuni; these are potential source of human infection. Isolation rate in developing countries is between 5-35%. This study aimed at finding prevalence of children with campylobacter infection among children with acute diarrhea attending Mulago hospital. OBJECTIVE: The objective was to establish the proportion of children infected with Campylobacter spp among children with acute diarrhea at Mulago hospital. METHODS: A crossectional study from July to October 2005 was conducted involved 226 children with acute diarrhea. Serial sampling was done a total of 226 stool specimens were obtained and cultured on selective media. Identification was done using biochemical test and susceptibility using standard discs diffusion method. RESULTS: Campylobacter spp were isolated in 21 (9.3%) of 226 stool specimens analyzed. Campylobacter jejuni 17 (80.9%), Campylobacter lari 2 (9.5%), Campylobacter coli 1 (4.5%) and Campylobacter jejuni/coli 1(4.5%). All Campylobacter isolates were sensitive to erythromycin, and 20% had intermediate resistance to Ampicillin. CONCLUSION: Campylobacter spp are prevalent among children with acute diarrhea in Kampala- Uganda. A large multicenter study should be undertaken so that the extent of campylobacter infection in our setting can be established. PMID- 20589153 TI - Health care related factors associated with severe malaria in children in Kampala, Uganda. AB - BACKGROUND: Severe malaria is responsible for the high load of malaria mortality. It is not clearly understood why some malaria episodes progress to severe malaria. OBJECTIVE: To determine factors associated with severe malaria in children aged 6 months to 5 years living in Kampala. METHODS: Over a 6-month period, 100 children with severe malaria were matched by age and place of residence with 100 children with non-severe malaria. We collected health care information from care takers. RESULTS: Mean duration of illness before getting antimalarial treatment was shorter for controls than cases (8 hours vs. 20 hours, p 0.015). Children with severe malaria were less likely to have been treated with sulphadoxine-pyrimethamine in the preceding 2 weeks (OR 0.2, 95% CI 0.04-0.85, p 0.016). Odds of severe malaria were higher in those who reported lack of protective measures (mosquito coils (OR = 20.63, 95% CI 1.5-283.3, p=0.02 and insecticide sprays OR 10.93, 95% CI 1.13-105.64, p=0.03), although few reported their use. CONCLUSIONS: Early anti-malarial treatment and use of barriers against mosquitoes prevent severe malaria in children. There is need to increase the use of barriers against mosquito bites and to scale up prompt treatment and community based interventions to reduce the incidence of severe malaria in children. PMID- 20589155 TI - The prevalence and severity of mental illnesses handled by traditional healers in two districts in Uganda. AB - BACKGROUND: Little is known about the prevalence and severity of DSM-IV mental disorders treated by traditional healers in Uganda. OBJECTIVE: To describe the prevalence and severity of DSM-IV disorders handled by traditional healers in Jinja and Iganga districts, Eastern Uganda. METHOD: Between January and March 2008, Face-to-Face Interviews were conducted with 400 patients attending traditional healers' shrines for mental health problems, using Self Rating Questionnaire 25 (SRQ-25) for screening, the Mini International Neuropsychiatric Interview (MINI-Plus) for specific DSM-IV diagnosis and the Global Assessment of Functioning (GAF) for severity of illness. Descriptive data analysis and frequency estimates were performed using SPSS version 15.0 for Windows. Pearson's chi-square tests and odds ratios were used to explore the relationship between severity and combined use of biomedical services and traditional healing. RESULTS: Of 387 respondents, 60.2% had diagnosable current mental illness and 16.3% had had one disorder in their lifetime. Of the diagnosable current mental illnesses, 29.7% were Psychosis; 5.4% Major depressive episode; 5.6% Anxiety disorders; 3.6% mixed Anxiety-Depression; and 3.9% Suicidality. In terms of severity, 37.7% of the current mental illnesses were severe, 35.1% moderate and 13.2% mild. Patients with moderate to severe symptoms were more likely to use both biomedical services and traditional healers. CONCLUSION: These findings suggest that a considerable number of patients with DSM-IV diagnosable mental disorders attend traditional healing shrines; the majority had moderate to severe symptoms. Mental health professionals therefore need to come up with ways to co operate with traditional healers, e.g. as officially designated Traditional Mental Attendants (TMA), for the benefit of their patients. PMID- 20589156 TI - Psychological distress and adherence to highly active anti-retroviral therapy (HAART) in Uganda: a pilot study. AB - BACKGROUND: Mental health related risk factors for non-adherence to highly active anti-retroviral therapy (HAART) have not been investigated in Uganda and yet adherence is critical to the success of the current scale up in the provision of HAART to HIV positive individuals in rural areas of Uganda. OBJECTIVE: To determine whether psychological distress is a risk factor for non-adherence to HAART among HIV positive individuals. METHOD: One hundred twenty-two HIV positive adult individuals receiving care from an Urban HIV clinic were enrolled in the study. Participants were screened for psychological distress with the Self Report Questionnaire (SRQ-20). Adherence was assessed using the self report method. Multivariate logistic regression analysis was used to determine whether psychological distress is a risk factor for non-adherence to HAART adjusting for various socio-demographic and clinical factors. RESULTS: Psychological distress and living in isolation were significantly associated with non-adherence to HAART after adjusting for other demographic and clinical variables [OR=3.66, 95%CI (1.39 - 9.78) and OR=9.80, 95%CI (2.27 - 18.70)] respectively. Among HIV positive individuals who were receiving additional treatment for a mental disorder, psychological distress was not significantly associated with non-adherence to HAART [OR= 1.25, 95%CI (0.30 - 5.20)] CONCLUSION: Regular screening and management of psychological distress may prevent further complications in HIV positive individuals in Uganda. PMID- 20589157 TI - Effect of glycaemic control on glomerular filtration rate in diabetes mellitus patients. AB - BACKGROUND: Glomerular filtration rate (GFR) is a widely accepted parameter in assessing overall renal function. This study sought to assess the effect of glucose lowering on GFR in diabetic patients admitted for short term therapy at Mulago hospital. METHODS: This was a descriptive study where consenting patients were consecutively recruited. Glomerular filtration rate was measured using creatinine clearance in 40 type I and II diabetes mellitus patients admitted on the basis of a glucometer reading of RBS >or= 300 mg/dl both at admission and discharge. Data was analyzed using a paired sample t-test and p-value set at 0.05 (95% CI). RESULTS: A total of 40 patients were assessed. Their mean age was 49.8 years. 82.5% of them had type II DM while only 17.5% had type I DM. The average duration of disease was 7 years. GFR was found to decrease from 157.4 ml/min on admission to 86.4 ml/min at discharge (p=0.001). Random blood sugar levels decreased from 332.2mg/dl on admission to 119.8 mg/dl at discharge (p=0.000). CONCLUSION/RECOMMENDATION: Results imply that glycaemic control lowers the GFR in diabetic patients admitted for short term treatment. A reduction in GFR reflects reduction of hyperfiltration, a process that starts diabetic nephropathy. Good glycaemic control will go along way to delay onset of diabetic nephropathy. PMID- 20589158 TI - Assessment of partogram use during labour in Rujumbura Health Sub District, Rukungiri District, Uganda. AB - BACKGROUND: A partogram is a universal tool for monitoring labour. It is used for labour management in Rujumbura HSD, Rukungiri District. However, the District Health Officer reported only 30% use of a partogram. The study intended to find out why the low use, and suggest strategies in scaling up. OBJECTIVES: To establish extent of use of a partogram, health facility and health workers' factors that affected its use during labour plus the relationship between foetal Apgar score and its use. MATERIALS AND METHODS: A cross-sectional study involving observations, record reviews and interviewing of staff in 8 health facilities (4 Public and 4 Private Not For Profit) in Rujumbura HSD in Rukungiri district was conducted from May 23(rd) to 27(th) June 2008. It employed both qualitative and quantitative methods of data collection. RESULTS: The partogram was used in 69.9% of deliveries. The partographs that fulfilled the standard monitoring of foetal heart rate were only 2%. There were few trained health workers and lack of guidelines on partogram use. A good Apgar score was associated with standard foetal monitoring and was statistically significant (P < 0.001). CONCLUSIONS AND RECOMMENDATIONS: There was poor use of partograms during labour mainly affected by health input factors. We recommended training of health workers on partogram use, provision of guidelines and adequate resources. PMID- 20589159 TI - Adaptation of the multidimensional scale of perceived social support in a Ugandan setting. AB - BACKGROUND: The Multidimensional Scale of Perceived Social Support (MSPSS) was developed in the USA. The adequacy of its use in Uganda to guarantee its reliability and validity has not been ascertained. AIM: Thus the aim of the present study was to adapt the MSPSS scale by testing the validity and reliability of the scale in a Ugandan setting. METHODS: A cross-sectional design was employed and 240 respondents were consecutively recruited from postnatal clinics in Mulago hospital. Analysis of reliability and validity of the adapted MSPSS was done. Cronbach alpha and principal component analyses were respectively generated. RESULTS: Three subscales of the MSPSS that had been identified in other populations were evident in the Ugandan population. Using the Cronbach's alpha, the MSPSS demonstrated good internal consistency at .83. A dendrogram indicated that all sub items of the MSPSS were inter-linked. Exploratory Factor analysis derived three components. Principal Component analysis using rotated varimax generated high loadings on all subscales. CONCLUSION: The adapted MSPSS can reliably be used in Uganda. PMID- 20589160 TI - In-vitro antibacterial activity of selected medicinal plants from Longisa region of Bomet district, Kenya. AB - BACKGROUND: Current strategies to overcome the global problem of antimicrobial resistance include research in finding new and innovative antimicrobials from plants. This study was carried out to determine the antibacterial activity of plant extracts of Olea africana stem-bark, Psidium guajava leaves, Vernonia amygdalina leaves, Lantana camara leaves and Mangifera indica leaves which are used in folklore medicine to treat infections of microbial origin in Longisa region of Bomet District, Kenya. METHODS: Methanol extracts were derived and screened. Standard cultures of Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 25923 were used in the study. The antibacterial tests used were the agar well diffusion assays at concentration 1 gm/ml. Minimum Inhibition Concentration (MIC) was determined in the plant extract that showed some efficacy against the tested microorganisms. Gentamicin (10 microg) was used as a positive control. RESULTS: The methanol extracts showed weak antibacterial activity against the study organisms compared to Gentamicin. All extracts exhibited a significant bactericidal activity against S. aureus while L. camara and V. amygdalina lacked efficacy against P.aeruginosa and E. coli. O. africana and P. guajava presented the lowest MIC against S.aureus (62.5 mg/ml and 250 mg/ml respectively P. guajava and M. indica showed analogous MICs against P.aeruginosa (250 mg/ml). P. guajava exhibited a better MIC against E.coli (500 mg/ml). CONCLUSIONS: This in-vitro study corroborated the antimicrobial activity of the selected plants used in folklore medicine. The plants could be potential sources of new antimicrobial agent. PMID- 20589161 TI - Non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara Hospital Uganda: prevalence and associated factors. AB - BACKGROUND: Non-adherence to treatment remains a major obstacle to efficient tuberculosis control in developing countries. The dual infection of Tuberculosis and HIV presents further adherence problems because of high pill burden and adverse effects. This poses a risk of increased multi-drug resistant TB. However, the prevalence of non-adherence and its associated factors have not been studied in these patients in Uganda. OBJECTIVES: To determine the prevalence and factors associated with non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara hospital. METHODS: A cross-sectional study with qualitative and quantitative data collection methods was conducted among TB/HIV co-infected adults in Mbarara hospital from January to March 2008. Consecutive sampling was used to select 140 participants. Adherence was assessed over a 5-day period prior to the interview using patients self-reports. Data was collected using an interviewer administered questionnaire. Qualitative data was collected through key informant interviews using a topic guide and was analyzed manually. Quantitative data was analyzed using STATA version 8. Logistic regression was used to determine factors associated with nonadherence. RESULTS: The prevalence of non-adherence was 25% (95% CI=17.8-32%). Being on continuous phase of the TB regimen was significantly associated with non-adherence (OR=6.24, p<0.001). Alcohol consumption, being on antiretroviral therapy and smoking confounded the relationship between stage of the TB regimen and non-adherence. CONCLUSION: The prevalence of non-adherence was high. Patients that are on continuous phase of TB treatment should be supported to continue taking their drugs. In addition, patients that drink alcohol; smoke and those not on ART should be targeted with interventions to improve adherence. PMID- 20589162 TI - Influence of hypoxia induced by minimally invasive prostatectomy on gene expression: implications for biomarker analysis. AB - Handling and processing of clinical specimens during and after surgical resection may significantly skew the molecular data obtained from analysis of those samples. Minimally invasive prostatectomy was used as a model to specifically study effects of surgical ischemia on gene expression in human clinical samples. Normal prostatic urethra cup biopsies were procured from 12 patients at three time points during laparoscopic radical prostatectomy. Homogeneous cells (stroma and epithelium) were microdissected. Transcript analysis of 3 oxygen-dependent, 3 oxygen-independent, and 3 control class genes was performed using quantitative RT PCR. Data were analyzed by relative quantitation and two-sided t-test. Patient demographic and time covariates were fit by a linear mixed model. VEGF, an oxygen dependent gene, showed significant expression alterations across three time points in epithelium (p=0.008), but not in stroma (p=0.66). Expression levels of VHL, STAT5B, and CYPA showed significant changes at the p<0.05 level in the stroma only. Effects of age, PSA, prostate size, Gleason score, surgery type, total surgery time, total ischemia time, and estimated blood loss on VEGF expression over time were not significant at the p<0.01 level. Therefore, surgical manipulation and tissue processing methods need to be taken into account when assessing prostatic biomarkers; however, resection does not dramatically alter mRNA profiles in prostate specimens. PMID- 20589163 TI - Multi-talented DEAD-box proteins and potential tumor promoters: p68 RNA helicase (DDX5) and its paralog, p72 RNA helicase (DDX17). AB - P68 (DDX5) and p72 (DDX17) are members of the DEAD-box RNA helicase family. They can unwind double-stranded RNA and also contribute to the remodeling of ribonucleoprotein complexes. These activities of p68/p72 are required for efficient RNA splicing and microRNA processing. In addition, p68/p72 perform functions that are independent of their enzymatic activity. This is especially common to their role in gene regulation, where p68/p72 coactivate various transcription factors, including the tumor suppressor p53, estrogen receptor alpha and beta-catenin. P68/p72 are posttranslationally modified by SUMO attachment and phosphorylation that regulate their coactivation potential, binding to known interactants or protein stability. Knock-out mouse models revealed that both DDX5 and DDX17 are essential genes during development. Furthermore, together with their ability to stimulate cell proliferation and prevent apoptosis, the reported overexpression of p68/p72 in three of the major human cancers (colon, breast, prostate) strongly suggests that p68/p72 promote tumorigenesis and might even represent proto-oncoproteins. If so, their inhibition holds promise as a novel way to contain or cure various carcinomas. PMID- 20589164 TI - Isopeptidases in anticancer therapy: looking for inhibitors. AB - Addition of polypeptides belonging to the ubiquitin family to selected lysines residues is a widespread post-translation modification (PTM) that controls many fundamental aspects of cell's life. Specific alterations in the normal turnover of this PTM are frequently observed in tumors. The conjugation/deconjugation cycle of ubiquitin (Ub) or ubiquitin-like (Ubl) proteins influences the activities of oncogenes and tumor suppressor genes. Two families of enzymes work in antagonizing manner to add or remove Ub and Ubl-proteins on target proteins: the E3 ligases and the isopeptidases. These enzymes are the subjects of fervent research with the ambition to comprehend their regulation, their mechanisms of action, their involvement in human diseases, and to develop specific inhibitors for therapeutic intervention. Here we will discuss of isopeptidases, the deconjugating enzymes, with particular emphasis on the proapoptotic activities of the relative inhibitors identified so far. PMID- 20589165 TI - Lithium inhibits carcinoid cell growth in vitro. AB - Carcinoids are slow growing neuroendocrine tumors that often cause debilitating symptoms due to excessive secretion of hormones such as serotonin. Surgery is the only potentially curative treatment, but many patients have unresectable metastatic disease. Lithium is a non- competitive inhibitor of GSK-3 with an established safety profile. The objective of this study was to investigate the effects of lithium on carcinoid cell growth in vitro. Lithium treatment caused a dose-dependent reduction in carcinoid cancer cell (BON and H727) growth. Western blot analysis revealed increased expression of cleaved poly (ADP-ribose) polymerase (PARP), indicating the induction of apoptosis. Lithium treatment also suppressed cellular levels of serotonin and chromogranin A. In summary, lithium inactivates GSK-3, induces apoptosis, and suppresses carcinoid cancer cell growth in vitro. The drug has been used clinically since the 19(th) century to treat a variety of diseases including bipolar disorder, and its safety profile is well documented. Therefore, based on these findings, we have undertaken a clinical trial of lithium chloride in the treatment of patients with unresectable carcinoid cancer. PMID- 20589167 TI - Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products. AB - Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cell-based therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cell based therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cell-based medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development. PMID- 20589168 TI - VX680/MK-0457, a potent and selective Aurora kinase inhibitor, targets both tumor and endothelial cells in clear cell renal cell carcinoma. AB - Aurora kinases are key regulators of cell mitosis and have been implicated in the process of tumorigenesis. In recent years, the Aurora kinases have attracted much interest as promising targets for cancer treatment. Here we report on the roles of Aurora A and Aurora B kinases in clear cell renal cell carcinoma (ccRCC). Using genomewide expression array analysis of 174 patient samples of ccRCC, we found that expression levels of Aurora A and B were significantly elevated in ccRCC compared to normal kidney samples. High expression levels of Aurora A and Aurora B were significantly associated with advanced tumor stage and poor patient survival. Inhibition of Aurora kinase activity with the drug VX680 (also referred to as MK-0457) inhibited ccRCC cell growth in vitro and led to ccRCC cell accumulation in the G2/M phase and apoptosis. Growth of ccRCC xenograft tumors was also inhibited by VX680 treatment, accompanied by a reduction of tumor microvessel density. Analysis of endothelial cell lines demonstrated that VX680 inhibits endothelial cell growth with effects similar to that seen in ccRCC cells. Our findings suggest that VX680 inhibits the growth of ccRCC tumors by targeting the proliferation of both ccRCC tumor cells and tumor-associated endothelial cells. Aurora kinases and their downstream cell cycle proteins have an important role in ccRCC and may be potent prognostic markers and therapy targets for this disease. PMID- 20589166 TI - Involvement of oxidatively damaged DNA and repair in cancer development and aging. AB - DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. PMID- 20589169 TI - Epidermal growth factor receptor gene amplification in atypical adenomatous hyperplasia of the lung. AB - Atypical adenomatous hyperplasia (AAH) is postulated to be the earliest morphologic precursor lesion in lung carcinogenesis. The epidermal growth factor receptor (EGFR), one of the members of the Erb-2 family of receptors, is commonly expressed in non-small cell lung carcinoma (NSCLC). A subset of the patients with NSCLC has molecular abnormalities in the EGFR gene, including missense mutations and deletions and/or abnormal gene copy numbers, and the relative importance of each of these for patient outcome is an area of great interest. Recent reports show that EGFR mutations are rare or absent in AAH and are rare in bronchioloalveolar carcinoma (BAC). However, the EGFR gene copy number status in AAH is unknown. In this study, we examined the EGFR gene copy number status in lung adenocarcinomas, synchronous AAH, and BAC in surgical pathology resection specimens. EGFR gene copy number was analyzed by chromogenic in situ hybridization (CISH) using formalin fixed paraffin embedded tissue sections and EGFR probes as recommended by the manufacturer. A known positive case of high grade glioma was used as a positive control. The results indicate that four of eight adenocarcinomas (50%) had more than five EGFR signals per nucleus, suggesting a gain in copy number. Interestingly, in four of nine cases of AAH (44.4%) more than three EGFR signals per nucleus were noted, with scattered cells showing up to 6 signals per nucleus. In addition, in five of 12 cases of BAC (42%), more than three EGFR signals per nucleus were noted. In the remaining cases two to three intranuclear dot-like peroxidase positive signals were present consistent with non-amplification of the gene. Our study reveals an abnormal EGFR gene copy gain in several cases of AAH. In our cohort, the rate of EGFR gene copy abnormalities in AAH appears similar to BAC and lower than in lung adenocarcinomas. These findings suggest that although EGFR gene copy abnormalities may be an early event in lung carcinogenesis, they are associated with tumor progression to invasive cancer and highlight the complexity of tumor morphogenesis. PMID- 20589172 TI - Removal of laryngeal mask airway: awake vs anesthetized. PMID- 20589170 TI - The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication. AB - A surplus of food supply has evoked a worldwide increase in incidence of type 2 diabetes. This trend will have a significant impact on the life span of people living in modern societies. In contrast, reduced calorie intake has significant impact on preventing type 2 diabetes and increasing longevity. Increased production of reactive oxygen species (ROS), resulting in oxidative stress, has long been proposed as a unifying mechanism linking nutrient excess and diabetes. This review describes the updated mechanism by which oxidative stress provoked by nutrient excess contributes to the development of insulin resistance and pancreatic betacell failure. However, despite the promising results in cellular and animal models, major clinical trials have failed to demonstrate beneficial effect of antioxidants on the prevention of type 2 diabetes or the degree of glycemic control in individuals with diabetes. Emerging evidence shows that ROS also function as an insulin-signaling molecule in normal physiology and casts doubt on the potential beneficial effect of antioxidants. The gap between basic research and clinical outcomes heightens the importance for elucidating the precise molecular mechanisms by which cellular redox status affects insulin signaling. PMID- 20589171 TI - Effects of combined hyperoxia and cyclooxygenase inhibition in neonatal rat lungs. AB - We examined the hypothesis that persistent pulmonary hypertension of the newborn (PPHN) associated with ibuprofen is due to alterations in biochemical and molecular regulators of oxidative stress and NO signaling. Newborn rats breathing 50% O2 or room air from the first day of life (P1), received early IP injections of: 1) indomethacin (0.2 mg/kg) on P1 and 0.1 mg/kg on P2 and P3; 2) ibuprofen (10 mg/kg) on P1 and 5 mg/kg on P2 and P3; or 3) saline on P1, P2 and P3, then euthanized on P4; or late treatment on P4, P5 and P6, then euthanized on P7. Lung biomarkers for oxidative stress (8- epi-PGF2a), DNA damage (8-hydroxy-2' deoxyguanosine) and pulmonary hypertension (ET-1, big ET-1, and total NO) were assessed. Despite timing of the dose and oxygen exposure, both drugs resulted in increased alveolar size. Both drugs had no beneficial effects on oxidative stress. Indomethacin treatment in O2 resulted in higher pulmonary levels of 8-epi PGF2alpha which was associated with downregulation of most antioxidant genes with early treatment and overexpression of GPX5 and 6 with late treatment. Early and late ibuprofen treatment suppressed hyperoxia-induced NOx production and downregulated iNOS. Postponing treatment had no significant beneficial effects on biomolecular regulators of oxidative stress and NO signaling. The effect of ibuprofen on pulmonary NOx may explain in part, the transient PPHN seen in ibuprofen-treated preterm infants. PMID- 20589173 TI - Difference of the hemodynamic changes induced by tracheal intubation using remifentanil between smokers and nonsmokers. AB - BACKGROUND: It was well-known that smoking affects the cardiovascular system, and remifentanil can suppress the sympathetic stimulations induced by tracheal intubation. The purpose of this study was to investigate whether there was any difference in the hemodynamic changes induced by tracheal intubation with using remifentanil between smokers and nonsmokers. METHODS: EIGHTY PATIENTS WERE ENROLLED: male smokers (MS), male nonsmokers (MN), female smokers (FS) and female nonsmokers (FN). Anesthesia was induced with diluted remifentanil (20 microg/ml) at a rate of 10 microg/kg/hr using an infusion pump, and 2 min later, midazolam 0.05 mg/kg and propofol 0.8 mg/kg were injected for achieving unconsciousness. Rocuronium 1 mg/kg was used for muscle relaxation, and tracheal intubation was performed 2 min after rocuronium injection. After tracheal intubation, the remifentanil was decreased to 2 microg/kg/hr. The mean arterial pressure (MAP) and heart rate (HR) were checked before induction, on unconsciousness, just before intubation, just after intubation and 1, 2 and 3 minutes after intubation, and these values were compared between the groups. RESULTS: In men, the MAP and HR just after intubation and at 1, 2 and 3 minutes after intubation in Group MS were significantly higher than those of Group MN (P < 0.05). For the women, the HR in both groups (the FS and FN groups) were increased just after intubation and 1, 2 and 3 minutes after intubation compared with that at the baseline, respectively, but there was no difference between the two groups. CONCLUSIONS: There was a difference of the hemodynamic changes induced by tracheal intubation with using remifentanil between the male smokers and nonsmokers, but not in women. PMID- 20589174 TI - Effects of anesthesia on fluid volume kinetics after infusion of colloid solution during blood donation. AB - BACKGROUND: The fluid kinetics of intravenously infused colloid during inhalation anesthesia and hemorrhage have not been investigated. We therefore assessed fluid space changes during infusion of hydroxyethyl starch solution after hemorrhage in conscious and desflurane-anesthetized individuals. METHODS: Following the donation of 400 ml of blood, 500 ml of hydroxyethyl starch solution was infused over 20 minutes into wakeful and desflurane-anesthetized volunteers. Blood was repeatedly sampled to measure hemoglobin concentration, a marker of plasma dilution, and fluid kinetic analysis was performed to evaluate changes in fluid space. RESULTS: Using a fluid kinetic model, we found that the mean volume of fluid space was 7,724 +/- 1,788 ml in wakeful volunteers and 6,818 +/- 4,221 ml in anesthetized volunteers, and the elimination rate constants were 7.1 +/- 3.5 ml/min and 19.4 +/- 4.6 ml/min, respectively. CONCLUSIONS: Infusion of colloid after mild hemorrhage resulted in similar expansions of plasma volume in desflurane-anesthetized and conscious individuals. During anesthesia, however, the expansion of plasma volume by colloid was decreased and of shorter duration than observed in conscious patients. PMID- 20589175 TI - A portable inhalational induction device provides co-operative induction of anaesthesia in preanaesthetic area for children. AB - BACKGROUND: We introduce a new, simple portable inhalational induction device (PD) that provides co-operative inhalational induction of anaesthesia using N(2)O and subsequent sevoflurane in the preanaesthetic induction area in children. METHODS: Forty-five children (30 to 94 months old age, <35 kg) who were scheduled to undergo simple operations were assigned randomly to one of three regimens. Patients were encouraged by their parents to inhale N(2)O followed by sevoflurane (PD N(2)O-sevo group) or sevoflurane (PD sevo group) using a portable inhalational induction device in the preanaesthetic induction area until they were unable to respond to their names. They were then transferred to the operating room while maintaining inhalation of sevoflurane via the device. The control group underwent conventional inhalational induction in the operating room with the parents in attendance. RESULTS: Patients in the PD N(2)O-sevo group had a higher co-operative inhalation frequency than the patients in the PD sevo or the control group. Anaesthesia induction in the PD N(2)O-sevo and the PD sevo groups were faster than in the control group. Parent satisfaction score (0-100) was higher for the PD N(2)O-sevo group than for the control group. CONCLUSIONS: A new portable inhalational induction device allows faster induction in co operation with parents present in the preanaesthetic induction area compared to conventional inhalational induction in the unfamiliar operating room with the parents in attendance. PMID- 20589176 TI - Caudal analgesia reduces the sevoflurane requirement for LMA removal in anesthetized children. AB - BACKGROUND: An anesthetic state can reduce adverse airway reaction during laryngeal mask airway (LMA) removal in children. However, the anesthetic state has risks of upper airway obstruction or delayed emergence; so possibly less anesthetic depth is advisable. Caudal analgesia reduces the requirement of anesthetic agents for sedation or anesthesia; it is expected to reduce the sevoflurane requirement for LMA removal. Therefore, we determined the EC(50) of sevoflurane for LMA removal with caudal analgesia and compared that to the EC(50) without caudal analgesia. METHODS: Forty-three unpremedicated children aged 1 to 6 yr were enrolled. They were allocated to receive or not to receive caudal block according to their parents' consent. General anesthesia were induced and maintained with sevoflurane and oxygen in air. EC(50) of sevoflurane for a smooth LMA removal with and without caudal analgesia were estimated by the Dixon up-and down method. The LMA was removed when predetermined end-tidal sevoflurane concentration was achieved, and the sevoflurane concentration of a subsequent patient was determined by the success or failure of the previous patient with 0.2% as the step size; success was defined by the absence of an adverse airway reaction during and after LMA removal. EC(50) of sevoflurane with caudal block, and that without caudal block, were compared by a rank-sum test. RESULTS: The EC(50) of sevoflurane to achieve successful LMA removal in children with caudal block was 1.47%; 1.81% without caudal block. The EC(50) were significantly different between the two groups (P < 0.001). CONCLUSIONS: Caudal analgesia significantly reduced the sevoflurane concentration for a smooth LMA removal in anesthetized children. PMID- 20589177 TI - A comparison of the hemodynamic changes and propofolinduced pain at two different doses of remifentanil in elderly patients. AB - BACKGROUND: The purpose of this study was to determine the optimal dose of remifentanil for minimizing hemodynamic changes during intubation and reducing propofol-induced pain in elderly patients. METHODS: In a randomized prospective study, 60 patients (ASA I-II, elder than 65 years) were enrolled to determine which of two target remifentanil blood concentrations (3 ng/ml, 5 ng/ml) was required to blunt hemodynamic changes during intubation and to reduce propofol induced pain. After the target effect site concentration of remifentanil had been reached, the target controlled infusion of propofol was started and propofol induced pain was recorded. Blood pressure and heart rate were recorded at baseline, just before intubation and 1, 3, 5 min after intubation. RESULTS: There were no significant differences in the hemodynamic parameters between two groups, but not in arterial pressure at just before intubation and 1 minute after intubation. However, the group R5 (5 ng/ml) showed significantly less intense pain induced by propofol than in the group R3 (3 ng/ml). CONCLUSIONS: The results suggest that the group R5 provide more relief in propofol induced pain than the group R3, but showed great possibility of hypotension and bradycardia in both groups, which means it should be used with cautions in the elderly patients. PMID- 20589178 TI - Continuous infusion of two doses of remifentanil immediately after laparoscopic assisted vaginal hysterectomy. AB - BACKGROUND: We evaluated the effect and safety of the immediate postoperative continuous infusion of remifentanil at two doses in patients undergoing laparoscopic-assisted vaginal hysterectomy (LAVH) with alfentanil-based patient controlled analgesia (PCA). METHODS: The study enrolled 50 ASA physical status 1 or 2 patients scheduled to undergo LAVH. Anesthesia was maintained with sevoflurane-remifentanil-air. At the last skin suture, the sevoflurane was discontinued, and patients were randomized to receive remifentanil 0.05 microg/kg/min (group I) or 0.1 microg/kg/min (group II). PCA was started at the time of eye opening and response to a verbal command. In the recovery room, we monitored the mean arterial blood pressure (MAP), heart rate (HR), respiratory rate (RR), SpO(2), and bispectral index (BIS) at 5-minute intervals. Thirty minutes after starting PCA, the remifentanil was discontinued. Pain was assessed using a visual analog scale (0 = no pain; 100 = the worst possible pain) at 0, 5, 10, and 30 minutes after stopping the remifentanil infusion. RESULTS: The eye opening time, BIS, MAP, and HR did not differ significantly between the two groups, and pain scores were similar between the two groups. Respiratory depression (SpO(2) < 90% or RR < 8/min) did not occur in group I but did occur in three patients in group II. CONCLUSIONS: Continuous remifentanil infusion (0.05 microg/kg/min) immediately postoperatively with alfentanil-based PCA had a similar effect as a 0.1 microg/kg/min infusion with respect to pain control without side effects. However, special attention must be given to respiratory depression. PMID- 20589179 TI - Spectral analysis of respiratory-related hemodynamic variables in simulated hypovolemia: a study in healthy volunteers with spontaneous breathing using a paced breathing activity. AB - BACKGROUND: A dynamic preload index such as stroke volume variation (SVV) is not as reliable in spontaneous breathing (SB) patients as in mechanically ventilated patients. This study examined the hypothesis that spectral analysis of hemodynamic variables during paced breathing (PB) activity may be a feasible index of volume changes and fluid responsiveness, despite insufficient respiratory changes in the preload index during SB activity. METHODS: Blood pressure and stroke volume (SV) were measured in 16 subjects undergoing PB (15 breaths/min), using a Finometer device and the Modelflow method. Respiratory systolic pressure variation (SPV) and SVV were measured and respiratory frequency (RF, 0.2-0.3 Hz) of power spectra of SPV (SPV(RF)) and SVV (SVV(RF)) were computed using fast Fourier transformation. Progressive hypovolemia was simulated with lower body negative pressure (LBNP). Volume challenges were produced by infusion of normal saline and subsequent release of LBNP to baseline. Fluid responsiveness, defined as a >20% increase in SV, was assessed by the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: Graded hypovolemia caused a significant increase in SPV(RF) and a decrease in SVV(RF). During volume expansion, SPV(RF) decreased and SVV(RF) rose significantly. Fluid responsiveness was better predicted with SVV(RF) (AUC 0.75) than with SPV(RF), SPV, or SVV. SVV(RF) before volume challenge was significantly correlated with volume expansion-induced changes in SV (r = -0.64). CONCLUSIONS: These results suggest that RF spectral analysis of dynamic preload variables may enable the detection of volume change and fluid responsiveness in SB hypovolemic patients performing PB activity. PMID- 20589180 TI - Hydrothorax due to extravasation of intravenous contrast through left subclavian catheter -A case report-. AB - Central venous catheterization is associated with a large number of complications, such as pneumothorax, hydrothorax, hemothorax, phlebothrombosis, pericardial tamponade, air embolism, aberrant placement and line sepsis. There are many case reports of the extravasation of various central venous catheter fluids, including the intravenous fluids, total parenteral nutrition and chemotherapeutic agents into the pleural cavity and mediastinum. These have led to hydrothorax, hydromediastinum and pericardial effusions. We report a case of the extravasation of intravenous contrast into the pleural cavity after dynamic CT through a left subclavian catheter. PMID- 20589181 TI - Rupture of abdominal aortic aneurysm after spine surgery in the patient with Ehlers-Danlos syndrome -A case report-. AB - Ehlers-Danlos syndrome (EDS) is a rare inherited disorder of the connective tissue that is characterized by hyperextensible skin, hypermobile joints and abnormalities of the cardiovascular system. A 15-year-old girl with Ehlers-Danlos syndrome underwent thoracolumbar surgery for deformity correction. After surgery, an abdominal aortic rupture occurred, and she complained of abdominal distension had an abdominal circumference of 80 cm. Abdominal computed tomography revealed a pseudoaneurysm and a large hematoma at the retroperitoneum. She died of a massive hemorrhage during subsequent abdominal aortic surgery. PMID- 20589182 TI - Prolonged paradoxical air embolism during intraoperative intestinal endoscopy confirmed by transesophageal echocardiography -A case report-. AB - Venous air embolism (VAE) during intestinal endoscopy is a rare complication. We report a case of cardiovascular collapse due to VAE confirmed by transesophageal echocardiography (TEE) during intraoperative intestinal endoscopy. TEE detected air bubbles in the left ventricle up to 1 hour after the event. When a patient deteriorates during endoscopic procedures, VAE and possible paradoxical air embolism (PAE) should be suspected. This case demonstrates that TEE can play an important role in diagnosing and managing an air embolism in anesthetized patients. In addition, this case demonstrates that PAEs may occur longer than expected after recovery from VAE-induced cardiovascular collapse. PMID- 20589183 TI - Anaphylactoid reaction after injection of ketorolac in a loading dose for patient controlled analgesia -A case report-. AB - Anaphylaxis is a severe and life-threatening systemic hypersensitivity reaction. Ketorolac is a popular drug used for patient-controlled analgesia. Although anaphylactic reaction to ketorolac has not been frequently reported, it can develop by way of several mechanisms. A 41-year-old male patient was scheduled for laparoscopic correction of a perforated gastric ulcer. Emergency surgery was performed under general anesthesia with no complications. Near the end of anesthesia administration, ketorolac in a loading dose was administered intravenously in order to launch patient-controlled analgesia. Following injection, urticaria-like skin lesions, including rashes and wheels appeared systemically; tachycardia and breathing difficulty with oxygen desaturation also developed. Through additional inquiry into the patient's drug history, past experience with ibuprofen allergy was identified. Antihistamine, steroid, and aminophylline were administered, and continuous positive airway pressure by full facial mask was applied to relieve bronchospastic symptoms. The patient recovered without further complications. PMID- 20589184 TI - Breakage of a thoracic epidural catheter during its removal -A case report-. AB - The breakage of an epidural catheter is a rare complication during the removal of a thoracic epidural catheter. There are many causes to breakage of an epidural catheter, such as the characteristics of the catheter itself, patient's factors (anatomy, position during insertion and removal of the catheter, and the BMI), and the difficulty of the procedure. Surgical removal is considered if there is a possibility that the retained catheter might cause neurological problems. We experienced a breakage of an epidural catheter during its removal, which led to surgical intervention. To prevent the catheter breakage during its removal, the catheter should be withdrawn without excessive tension. In addition, an understanding of the patient's anatomy is essential. PMID- 20589185 TI - Role and cost effectiveness of PET/CT in management of patients with cancer. AB - PET/CT is a relatively new imaging technology, whose undoubted advantages are valuable in clinical oncology as well as in all fields of diagnosis, staging, and treatment. The hardware combination of anatomy and function has been the true evolution in imaging. PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of solid malignancies, including colon, lung, etc., but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. However, controversy still exists in relation to the application of PET/CT in clinical practice, mainly because of its high cost. It is evident that apart from additional costs, potential savings also are associated with PET/CT as a result of avoiding additional imaging examinations or invasive procedures and by helping clinicians make the optimum treatment decisions. The authors review the literature on the role of PET/CT in management of various tumors and discuss the medicoeconomic usefulness. PMID- 20589186 TI - Expressive aphasia as a presentation of encephalitis with Bartonella henselae infection in an immunocompetent adult. AB - OBJECTIVE: To show the first clinically reported case of Cat Scratch Disease (CSD) presenting as a focal neurologic deficit in an immunocompetent adult. PATIENT: 59-year-old male with a history of a previous stroke. RESULTS: Examination showed an expressive aphasia, word substitution errors, and impaired repetition. A head CT and MRI showed no acute changes. The EEG findings were non focal and did not show any epileptiform activity. The patient had a history of contact with stray kittens and previous axillary lymphadenopathy. Bartonella henselae serology titers were IgG positive 1:1024 (< 64) and IgM positive 1:20 (< 16). After antibiotic administration, the patient's symptoms and aphasia resolved. CONCLUSIONS: Focal presentations concerning for stroke or partial seizure activity may have underlying infectious etiology. We recommend consideration of CSD in the differential diagnosis of any adult with a history of lymphadenopathy, fever, and recent contact with a cat who presents with neurologic complications. PMID- 20589187 TI - A rare case of de novo gigantic ovarian abscess within an endometrioma. AB - We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one. PMID- 20589188 TI - The yellow fever vaccine: a history. AB - After failed attempts at producing bacteria-based vaccines, the discovery of a viral agent causing yellow fever and its isolation in monkeys opened new avenues of research. Subsequent advances were the attenuation of the virus in mice and later in tissue culture; the creation of the seed lot system to avoid spontaneous mutations; the ability to produce the vaccine on a large scale in eggs; and the removal of dangerous contaminants. An important person in the story is Max Theiler, who was Professor of Epidemiology and Public Health at Yale from 1964 67, and whose work on virus attenuation created the modern vaccine and earned him the Nobel Prize. PMID- 20589189 TI - Five classic articles in genetic epidemiology. AB - The relatively new field of genetic epidemiology has witnessed some exciting leaps forward in our quest to understand the population and familial nature of genetic inheritance. We have witnessed the mapping of thousands of genetic loci contributing to both mendelian and complex diseases, and new high-throughput, low cost sequencing technologies promise to uncover even more. Here I highlight five publications that have shaped how we think about and conduct the task of unraveling the genetic causes of disease on a population scale. PMID- 20589190 TI - Perspectives on efficiency and quality in an ever changing system: Healthcare 2010. AB - The Healthcare 2010 conference at the Omni New Haven Hotel at Yale in April focused on how different stakeholders in the healthcare industry can excel in light of the recent landmark health-reform bill. A session titled "Maintaining Efficiency and Quality in an Ever Changing System" provided valuable insights into several perceptions of these two tenets, with respect to both the current state of U.S. healthcare and the recent reform. The engaging dialog that ensued concerning payer, provider, public, and patient perspectives yielded a unique view of the dynamic interplay between efficiency and quality in the context of the current healthcare system. While the discussion highlighted differences in the definitions of efficiency and quality upheld by the various players, a unifying theme emerged: In order to excel in this ever changing system, incentive structures will have to evolve to take full advantage of the potential synergies between the two. PMID- 20589191 TI - Follow-on biologics: a new play for big pharma: Healthcare 2010. AB - The U.S. pharmaceutical industry plays a vital role in shaping the face of American healthcare. As an industry rooted in innovation, its continued evolution is inherent. With major patent expirations looming and thin product pipelines, the industry now must consider new directions to maintain growth and stability. Follow-on biologics, derived from living organisms and marketed after the patent expiration of similar therapies, represent a growing opportunity for big pharmaceutical firms, as discussed during Yale's Healthcare 2010 conference in April. Key characteristics of follow-on biologics make them a worthwhile investment for big pharma companies: They command high prices, will likely have fewer entrants than generics due to high barriers to entry, and play to the existing strengths of big pharma firms. With the recent healthcare legislation providing the way for consistent Food and Drug Administration (FDA) regulation, the timing seems right to continue the push into this new and growing market. PMID- 20589193 TI - Cytogenetic abnormalities and azoospermia factor (AZF) microdeletions in infertile men from Kuwait. PMID- 20589192 TI - Gain weight by "going diet?" Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. AB - America's obesity epidemic has gathered much media attention recently. A rise in the percent of the population who are obese coincides with an increase in the widespread use of non-caloric artificial sweeteners, such as aspartame (e.g., Diet Coke) and sucralose (e.g., Pepsi One), in food products (Figure 1). Both forward and reverse causalities have been proposed. While people often choose "diet" or "light" products to lose weight, research studies suggest that artificial sweeteners may contribute to weight gain. In this mini-review, inspired by a discussion with Dr. Dana Small at Yale's Neuroscience 2010 conference in April, I first examine the development of artificial sweeteners in a historic context. I then summarize the epidemiological and experimental evidence concerning their effects on weight. Finally, I attempt to explain those effects in light of the neurobiology of food reward. PMID- 20589194 TI - A novel frameshift mutation in exon 12 of the adenomatous polyposis coli gene in an Italian family with familial adenomatous polyposis and desmoid tumour. PMID- 20589195 TI - Sudden death in pediatric populations. AB - Sudden death (SD) in children is rarer than in adults. In the pediatric population, SD accounts for less than one tenth of deaths from all causes. SD in infants is a separate entity commonly termed "sudden infant death syndrome (SIDS)". Previous studies on SD in pediatric patients primarily focused on infants and showed that the incidence of SIDS was much lower in Asian countries than in Western ones. However, these differences diminished after educational campaigns such as the back to sleep act in the late 1980s to early 1990s. The incidence of SIDS from Western reports has decreased from 2.69 to around 0.5-0.24 per 1,000 live births. Beyond infancy, the annual incidence of SD ranges from 1.3 to 7.5 per 100,000. In 2009, two population-based studies, one from Taiwan and the other from the US, explored the epidemiological profile of SD in children. The child health care indexes of these two countries are similar, but the annual incidence of pediatric SD was 7.5 and 2.7 per 100,000 in the USA and Taiwan, respectively. The implications of ethic-related differences requires further confirmation. Around 40% of pediatric SD could be from cardiac causes, either diagnosed or undiagnosed. Risk stratification for cardiac SD and patient selection for implantable cardioverter-defibrillator (ICD) therapy are recommended. However, the adoption of ICD as primary prevention for SD in children is still a challenging issue. Early detection of undiagnosed cardiac risk may be facilitated by cardiac screening either in newborns or the school-age population to better manage the risk of SD. However, the efficacy of such screening remains still controversial. PMID- 20589196 TI - Stress-induced cardiomyopathy: a need for prospective multicenter trials. PMID- 20589197 TI - The impact of mitral annular calcification on left ventricular function in nonagenarians. AB - BACKGROUND AND OBJECTIVES: Mitral annular calcification (MAC) is known to be associated with degenerative processes of the cardiac fibrous skeleton and cardiovascular disease mortality. However, MAC has not been evaluated in an extreme age group (patients >/=90 years of age). In this study, the clinical significance of MAC associated with aging was examined in this age group and compared with MAC associated with aging in a younger (20 to 50 years of age) group of patients. SUBJECTS AND METHODS: We assessed echocardiographic parameters in 43 nonagenarians and 51 young patients. In the nonagenarian group, patient's age was 92+/-2 years and 27% were male; in the young control group, patient's age was 36+/-9 years and 51% were male. Comprehensive M-mode and Doppler echocardiography, including tissue Doppler imaging, were performed. The frequency and severity of MAC was assessed from the leading anterior to the trailing posterior edge at its largest width for least 3 cardiac cycles. RESULTS: Echocardiography showed that the left ventricular (LV) end-diastolic dimension was larger in the young controls (p=0.007); however, the ejection fraction (EF) was lower in the nonagenarian group (p=0.001). The frequency of MAC was greater in nonagenarians {42/43 (97%)} than in controls {9/51 (17%), p<0.0001}. The maximal width of MAC was larger in nonagenarians (0.52+/-0.17 mm and 0.05+/-0.13 mm, p<0.0001). MAC was correlated with LV mass index (g/m(2)) (r=0.280, p=0.014) and EF (%) (r=-0.340, p=0.001). More importantly, early mitral inflow velocity/early diastolic mitral annulus velocity (E/E') was strongly correlated with MAC in non-agenarians (r= 0.683, p<0.0001). CONCLUSION: MAC may be associated with extreme age and increased LV filling pressure in nonagenarians. Further study is necessary to assess the cardiovascular mortality and structural changes related to mitral annulus calcification associated with aging. PMID- 20589198 TI - The correlation between left ventricular failure and right ventricular systolic dysfunction occurring in thyrotoxicosis. AB - BACKGROUND AND OBJECTIVES: Heart failure rarely occurs in patients with thyrotoxicosis (6%), with half of the cases having left ventricular dysfunction (LVD). Although a few studies reported isolated right heart failure in thyrotoxicosis, there has been no evaluation of relationship between LVD and right ventricular dysfunction (RVD). SUBJECTS AND METHODS: We enrolled 12 patients (mean age: 51+/-11 years, 9 females) diagnosed as having thyrotoxicosis with heart failure and LVD {left ventricular ejection fraction (LVEF) <40%}, and divided them into two groups {Group I with RVD defined as tricuspid annular plane excursion (TAPSE) less than 15 mm and Group II without RVD}. Clinical features, laboratory variables, and echocardiographic parameters were compared between two groups. RESULTS: RVD was found in 6 (50%) patients. On admission, there were no significant differences between the two groups in clinical features, laboratory variables, or echocardiographic parameters including atrial fibrillation {6 vs. 5, not significant (NS)}, heart rate (149+/-38 vs. 148+/-32/min, NS), LVEF (36.7+/-9.5 vs. 35.1+/-6.3%, NS), or the tricuspid regurgitation peak pressure gradient (TRPPG, 30.9+/-2.0 vs. 36.3+/-9.3 mmHg, NS). After antithyroid treatment, all achieved an euthyroid state and both ventricular functions were recovered. All data, including the recovery time of LVEF and the change of heart rate between two groups, displayed no significant differences. CONCLUSION: In half of patients, RVD was combined with thyrotoxicosis-associated LVD. There were no differences in clinical factors or hemodynamic parameters between patients with and without RVD. This suggests that RVD is not secondary to thyrotoxicosis associated LVD. PMID- 20589199 TI - Carotid Intima-Media Thickness, Not Carotid Plaque, is Associated With Large Territory Cerebral Infarction in Patients With Ischemic Stroke. AB - BACKGROUND AND OBJECTIVES: Carotid intima-media thickness (IMT) has been associated with an increased risk of ischemic stroke. To better understand this association, we evaluated the relationships of vascular risk factors, including carotid IMT and carotid plaque, and large territory cerebral infarction and small vessel stroke. SUBJECTS AND METHODS: A total of 502 patients with acute ischemic stroke were divided into two groups according to neurologic examinations and imaging studies; 1) a large territory infarction group (group I: n=126, 64.4+/-11 years, 78 males) and 2) a small vessel stroke group (group II: n=376, 62.5+/-11 years, 242 males). We evaluated associations between (a) territory and non territory strokes and (b) age, sex, potential vascular risk factors, carotid image and cardiac function (by echocardiography). RESULTS: We did not find significant between group differences of age, sex, diabetes, previous history of ischemic stroke, plaque (presence, site and size of carotid plaque), and velocity of carotid blood flow and left ventricle ejection fraction. However, group I had a higher incidence of hypertension (p=0.006), smoking (p=0.003), and dyslipidemia (p=0.001). Group I had thicker carotid IMT than group II (right carotid: 0.81+/ 0.21 mm vs. 0.76+/-0.19 mm, p=0.035; left carotid: 0.88+/-0.23 mm vs. 0.80+/-0.20 mm, p=0.014) and a higher e/e' level (12.08 vs. 9.66, p<0.001). Dyslipidemia, thicker carotid IMT and elevated E/E' ratios were significant independent predictors for large territory infarction in patients with ischemic stroke. CONCLUSION: Carotid IMT is significantly increased in patients with large territory infarction compared with those with small vessel stroke. PMID- 20589200 TI - Clinical characteristics and prognostic factors of stress-induced cardiomyopathy. AB - BACKGROUND AND OBJECTIVES: Stress-induced cardiomyopathy (SCM) is characterized by a transient left ventricular (LV) dysfunction due to emotional and physical stress. There are limited data about the clinical characteristics in Korean patients. We sought to clarify the clinical features and prognosis in patients with SCM. SUBJECTS AND METHODS: We reviewed 39 cases diagnosed with SCM in a tertiary hospital. The SCM was diagnosed as: 1) no previous history of cardiac disease, 2) acute onset, 3) regional wall motion abnormality, typically in the takotsubo or inverted takotsubo shape by echocardiography, and 4) no significant stenosis in the coronary angiogram. We evaluated clinical characteristics, biomarkers, and prognosis. RESULTS: Mean age was 61.3+/-16.1 years (female 69%). The triggering factors were physical stress in 32 patients (82%) and emotional stress in 5 patients (13%). The initial symptom was dyspnea (n=18, 46%) rather than chest pain (n=10, 26%). An initial electrocardiogram (EKG) presented T-wave inversion (n=18, 46%), ST-elevation (n=11, 28%), and ST-depression (n=2, 5%). Multivariate logistic regression analysis showed that initial high sensitive C reactive protein (hs-CRP) {odds ratio (OR) 1.41, 95% confidence interval (CI); 1.02-1.97} and initial left ventricular ejection fraction (LVEF) (OR 0.89, 95% CI; 0.80-0.98) were significantly associated with death or cardiogenic shock, respectively. CONCLUSION: The major triggering factor of SCM is physical stress due to illness or surgical procedures, and the first manifestation is dyspnea rather than chest pain. Elevated hs-CRP and decreased LVEF at admission were independent risk factors for death or cardiogenic shock. PMID- 20589201 TI - Affects of "age at diagnosis" on coronary artery lesions in patients with incomplete kawasaki disease. AB - BACKGROUND AND OBJECTIVES: Diagnosis of Kawasaki disease (KD) is based on 5 clinical features. Incomplete KD (IKD), which has fewer features, is more common in infants and older children, in whom the rate of coronary artery aneurysms is paradoxically higher. We conducted this study to evaluate risk factors associated with age-at-diagnosis on coronary arterial lesions (CAL) in patients with IKD. SUBJECTS AND METHODS: Retrospective data from 396 patients with KD in a single center were collected from January 2003 to July 2007. Patients were grouped according to their age at diagnosis; Group A (<1 year of age), Group B (1/=5 years of age). RESULTS: Among a total of 396 patients with KD, 87 (22.0%) were in Group A, 246 (62.1%) in Group B, and 63 (15.9%) in Group C. In groups A and C, lag times for starting intravenous immunoglobulin (IVIG) were longer than in Group B. There were no differences in the incidence of IKD, late CAL, or rates of IVIG retreatment among the three groups. Among 174 patients with IKD, there were no age-related differences in late CAL incidence or IVIG retreatment. Compared with typical KD, duration of fever and lag times to start IVIG were longer, and the rate of IVIG retreatment was higher in IKD, but there was no difference in the risk of CAL between typical KD and IKD. CONCLUSION: In the management of KD, especially the incomplete type, age-associated factors appear not to be significant for predicting the development of CAL. PMID- 20589202 TI - Successful carotid stenting for chronic total occlusion of the internal carotid artery. AB - A 64-year-old man complaining of pulsatile headache was admitted. Imaging studies revealed a near-total occlusion of the right proximal internal carotid artery (ICA) with slow antegrade flow into the distal ICA. Right cerebral flow was supplied by collateral flow through the posterior communicating and ophthalmic arteries. He was successfully treated by carotid artery stenting. No new neurological deficit or transient ischemic attack occurred after treatment. PMID- 20589203 TI - Successful treatment of an iatrogenic giant femoral artery pseudoaneurysm with percutaneous thrombin injection. AB - A femoral artery pseudoaneurysm (FAP) is one of the most troublesome complications following invasive procedures related to the femoral arterial access. Post-procedure FAP rarely occurs; however, its occurrence tends to increase with the more frequently antiplatelet agents, anticoagulants, and larger sized catheter used for interventional procedures. Traditionally, surgical repair has been considered as the standard treatment modality for FAP; however, less invasive methods currently exist such as blind manual or ultrasound-guided compression repair (UGCR) as well as percutaneous thrombin injection, both of which have replaced the need for surgery. We report a case of a giant pseudoaneurysm in a femoral artery, which had developed as a complication of stenting in a patient with carotid artery stenosis and ischemic heart disease, and was subsequently successfully treated using percutaneous thrombin injection. PMID- 20589204 TI - Real-time 3-dimensional echocardiography of the heart 13 years after partial left ventriculectomy. PMID- 20589205 TI - Fractured neck of femur--internal fixation versus arthroplasty. AB - BACKGROUND: Surgery is the treatment of choice for fractured neck of femur. For middle-aged patients (aged ca. 40 to 65), there is considerable debate over the indications for arthroplasty or internal fixation. The choice of surgical technique varies widely from one region to another. In this article, we discuss the main criteria that should be used in making this decision. METHODS: We selectively reviewed the literature on the diagnosis and treatment of fractured neck of femur, including the current guideline of the German Society for Trauma Surgery (Deutsche Gesellschaft fur Unfallchirurgie, DGU) and recent findings from the field of health services research. RESULTS: The treatment of middle-aged patients with dislocated fractures should be based on rational decision-making. The patient's level of activity before the accident should be judged in terms of his or her previous mobility, independence in daily activities, and mental status. Internal fixation is recommended if the fracture can be adequately repositioned, the bone is of good quality, and there is no evidence of osteoarthritis. Fractures that are more than 24 hours old should be treated with total hip arthroplasty. Hemiprostheses are appropriate for very old patients. Physically frail, bedridden, and/or demented patients should undergo internal fixation of the fracture. For non-displaced or impacted fractures, functional treatment (i.e., prophylactic securing of the fracture with screws or nails) is indicated. Rapid diagnosis and a short time in bed before surgery lower the rate of complications. Internal fixation with preservation of the femoral head should ideally be performed within the first 6 hours of trauma, and within the first 24 hours at most. CONCLUSION: Despite the increasing scarcity of resources, treatment should still be based on well-founded clinical guidelines. Minimally invasive surgery enables better function in the early postoperative phase and can thereby lower complication rates. An interdisciplinary concept for the postoperative care of elderly patients also has a major effect on the outcome. PMID- 20589206 TI - Recurrent angioedema and the threat of asphyxiation. AB - BACKGROUND: Recurrent angioedema may affect the skin or, less commonly, the tongue, gastrointestinal tract, and larynx. Angioedema is a clinical sign that can be produced by a variety of diseases. Asphyxiation due to edematous obstruction of the upper airway is rare, but, for the affected patients, it is a permanent risk. METHODS: Review of the literature based on a selective search and the authors' decades of experience treating patients with angioedema in a dedicated ambulatory care unit. RESULTS: Hereditary angioedema due to C1 esterase inhibitor deficiency has been intensively studied, and nearly all steps in its pathogenesis are known, from the causative gene defect all the way to the clinical presentation of angioedema. Bradykinin is the main mediator in this pathway. New treatment options (icatibant; C1-inhibitor concentrate for self administration and long-term treatment) have helped patients considerably. In recent years, a new type of hereditary angioedema has been described, resulting not from a lack of C1 inhibitor, but rather from mutations of coagulation factor XII or other, as yet unidentified genetic abnormalities. There are major differences in the pharmacological treatment of the different diseases that cause angioedema. In an emergency, when severe upper airway obstruction can be life threatening, immediate treatment is needed to keep the upper airway open. CONCLUSION: In patients with recurrent angioedema, the diagnostic classification of the underlying disorder as a particular type of hereditary or acquired angioedema is a prerequisite for appropriate treatment. PMID- 20589207 TI - Only sparse data are available for elderly patients. PMID- 20589208 TI - Nephrotoxic chemotherapy. PMID- 20589210 TI - Variables should be pre-set. PMID- 20589211 TI - Differences should be clarified. PMID- 20589213 TI - Liver abscess after common hepatic artery embolization for delayed hemorrhage following pancreaticoduodenectomy: a case report. AB - A 55-year-old man underwent pancreaticoduodenectomy for bile duct carcinoma in March 2009. The patient developed anastomotic leakage and had a short episode of hemorrhage from the drainage tubes with spontaneous disappearance. CT and upper endoscopy did not reveal the source of bleeding. A massive life-threatening hemorrhage occurred on the 18th postsurgical day. Emergency angiography showed a 2.7-cm pseudoaneurysm of the gastroduodenal artery stump, and hepatic artery embolization was performed. After embolization, an abscess appeared in segments 2/3 of the liver without involving the right lobe. We treated conservatively by drainage and antibiotics. During the course of therapy after embolization, the patient experienced several episodes of high fever but did not develop hepatic failure. On the 68th day after embolization, the abscess had penetrated to the lesser sac, which was immediately treated by percutaneous drainage. Anastomotic leakage was treated by continuous irrigation from the drain, for which complete resolution was achieved by the 34th day after embolization. The patient was discharged 101 days after embolization. Imaging and the clinical course demonstrate a unique mechanism of abscess formation after embolization. PMID- 20589214 TI - Benign fibrous histiocytoma of the buccal mucosa: case report and literature review. AB - Benign fibrous histiocytoma is an interesting and challenging entity even in its most usual, cutaneous presentation. Noncutaneous presentation is extremely limited, even more so for the mucosa of the head and neck area. We herein report such a case, describing the clinical characteristics of the lesion, complete diagnostic evaluation, management, and follow-up. Diagnostic histopathological challenges are specifically illustrated. A complete review of the relevant literature is also included. PMID- 20589215 TI - A Case of Villoglandular Papillary Adenocarcinoma of the Uterine Cervix Diagnosed during Early Pregnancy Followed by Successful Term Delivery. AB - Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Only five cases of VPA and pregnancy have been reported. Herein, we report a case of VPA diagnosed during early pregnancy and managed successfully with conservative measures; our patient delivered a healthy baby in full term. A successful pregnancy can be completed in patients with VPA without lymph-vascular invasion, when treated conservatively. This management is particularly desirable in young women to preserve reproductive capability. PMID- 20589216 TI - Pneumocephalus associated with cerebrospinal fluid fistula as a complication of spinal surgery: a case report. AB - Pneumocephalus is a well-known condition following head trauma, but is rare as an injury or as a result of surgery of the spine. We present a 76-year-old patient with a rare case of pneumocephalus associated with a cerebrospinal fluid fistula as a complication of surgical treatment for cervical myelopathy. Although cerebrospinal fluid leakage was noted and the injured dura was carefully sutured at operation, tension pneumocephalus occurred. The resultant pneumocephalus was diagnosed based on neurogenic symptoms including sudden convulsion, head radiograph, and computed tomography scan. The benign course of the pneumocephalus postdiagnosis did not require secondary operation. PMID- 20589217 TI - Sclerosing variant of the bronchioloalveolar carcinoma: imaging findings in an atypical case. AB - Bronchioloalveolar carcinoma remains one of the most enigmatic lung cancers, demonstrating varied growth patterns, mixed histological features, and confusing clinical manifestations. This paper reports a case of an unusual form of presentation: a sclerosing type associated with desmoplastic reaction and cicatrization. A 75-year-old woman was admitted with persistent dry cough and progressive dyspnea. Physical examination showed bilateral inspiratory crackles. A chest radiograph and high-resolution computed tomography demonstrated confluent airspace nodules, forming areas of consolidation in both lungs, with signs of architectural distortion. The lung biopsy revealed a nonmucinous sclerosing bronchioloalveolar carcinoma. PMID- 20589218 TI - Pulmonary Embolism Mimicking Pneumonia in a HIV Patient. AB - Recent studies have shown an increased risk of arterial and venous vascular diseases in HIV patients, pulmonary thromboembolism being one of them. HIV infected individuals may have procoagulants predisposing them to thromboembolism. Patients with thromboembolism may have a clinical presentation mimicking common opportunistic infections. It is important to consider pulmonary embolism in the differential of HIV patients with fever, cough, and dyspnea, particularly in those with well-controlled HIV infection. PMID- 20589219 TI - Fatal Septicaemia Following Suprapubic Cystostomy in a Paraplegic Patient: Never Do a Cystostomy without Prior Urine Culture and Appropriate Antibiogram! AB - Neuropathic urinary bladder is often colonised by multidrug-resistant bacteria. We report a 64-year-old male spinal cord injury patient with paraplegia, who received gentamicin on empirical basis before undergoing suprapubic cystostomy, as antibiotic sensitivity report of urine was not available. This patient developed fulminate septicaemia. Although appropriate antibiotic therapy (meropenem) was started when this patient manifested features of sepsis, acute renal failure occurred and he expired. Inappropriate initial antimicrobial therapy was the major contributory factor for this patient's mortality. Learning points from this case are (1) never do a cystostomy without prior urine culture and appropriate antibiogram; (2) in a chronic spinal cord injury patient, full blood count, liver function tests, albumin level, and albumin to globulin ratio should be performed before any surgical procedure. PMID- 20589220 TI - Ovarian splenosis: a case report. AB - Splenosis is auto transplantation of splenic tissue following traumatic rupture of the spleen. In females it can mimic endometriosis when symptomatic. Asymptomatic splenosis is common than previously suspected and it can also involve ovary. In a patient with a history of splenectomy, splenosis can act and provide the function of the spleen and thus should not be routinely excised. We report a case of an asymptomatic, incidental ovarian splenosis of left ovary accompanying multiple pelvic and serosal splenotic nodules. To our best knowledge, total three cases of ovarian splenosis have been reported previously including two cases of ovarian splenosis accompanying pelvic and serosal splenotic nodules and one case of solitary ovarian splenosis. PMID- 20589221 TI - Prolonged neuromuscular blockade following succinylcholine administration to a patient with a reduced butyrylcholinesterase activity. AB - This case is about a 48-year-old woman known with a reduced butyrylcholinesterase activity, who developed prolonged neuromuscular blockade following the unintentional administration of succinylcholine. We took the opportunity to monitor the development of neuromuscular function during this period and blood samples were taken for molecular genetic analysis and for quantitative and qualitative analysis since not all causative mutations are functionally characterized. Reduced butyrylcholinesterase activity is discussed in many aspects. Clinical considerations are suggested concerning genetic counselling. PMID- 20589222 TI - Screening Experiments for Developing Dynamic Treatment Regimes. AB - Dynamic treatment regimes are time-varying treatments that individualize sequences of treatments to the patient. The construction of dynamic treatment regimes is challenging because a patient will be eligible for some treatment components only if he has not responded (or has responded) to other treatment components. In addition there are usually a number of potentially useful treatment components and combinations thereof. In this article, we propose new methodology for identifying promising components and screening out negligible ones. First, we define causal factorial effects for treatment components that may be applied sequentially to a patient. Second we propose experimental designs that can be used to study the treatment components. Surprisingly, modifications can be made to (fractional) factorial designs - more commonly found in the engineering statistics literature -for screening in this setting. Furthermore we provide an analysis model that can be used to screen the factorial effects. We demonstrate the proposed methodology using examples motivated in the literature and also via a simulation study. PMID- 20589223 TI - Skills-Based, Interactive Computer Interventions to Prevent HIV Infection Among African-American and Hispanic Adolescents. AB - The spread of the acquired immunodeficiency virus (AIDS) virus, human immunodeficiency virus (HIV) infection, is increasingly evident. Despite the attention that HIV infection has received, few effective prevention strategies have been developed. The present paper reviews the epidemiology of AIDS among African-American and Hispanic adolescents. From epidemiological data, the authors argue for preventive approaches to reduce the risks of HIV transmission among African-American and Hispanic adolescents. Emphasizing culturally sensitive prevention strategies, the authors describe an intervention for these adolescents that combines skills-based and interactive computer approaches. PMID- 20589224 TI - Attentional Bias Differences between Fear and Disgust: Implications for the Role of Disgust in Disgust-Related Anxiety Disorders. AB - Research demonstrates a relation between disgust and anxiety-related pathology; however, research has yet to reveal mechanisms by which disgust may contribute to anxiety. The current experiment examined attentional bias characteristics as one route by which disgust influences anxiety. Eighty undergraduate participants completed a rapid serial visual presentation attention task using fear, disgust, or neutral target stimuli. Task-relevance of the target's presentation was also manipulated. Results revealed that task-relevant disgust targets impaired attention among all participants, but task-irrelevant disgust targets impaired attention only in high disgust prone individuals. Difficulty in disengagement characterized both disgust and fear attentional biases, but the difficulty in disengagement was greater for disgust compared to fear attentional biases. High disgust prone individuals displayed exaggerated difficulty in disengaging attention from disgust targets compared to low disgust prone individuals. The results suggest that disgust attentional biases differ from fear attentional biases. The characteristics of disgust attentional biases are discussed as possible mechanisms by which disgust functions in certain anxiety disorders. PMID- 20589225 TI - REACTIVE AND PROACTIVE AGGRESSION IN ADOLESCENT MALES: Examining Differential Outcomes 10 Years Later in Early Adulthood. AB - There is limited knowledge about the unique relations between adolescent reactive and proactive aggression and later psychosocial adjustment in early adulthood. Accordingly, this study prospectively examined associations between adolescent (mean age = 16) reactive and proactive aggression and psychopathic features, antisocial behavior, negative emotionality, and substance use measured 10 years later in early adulthood (mean age = 26). Study questions were examined in a longitudinal sample of 335 adolescent males. Path analyses indicate that after controlling for the stability of the outcome and the overlap between the two subtypes of aggression, reactive aggression is uniquely associated with negative emotionality, specifically anxiety, in adulthood. In contrast, proactive aggression is uniquely associated with measures of adult psychopathic features and antisocial behavior in adulthood. Both reactive and proactive aggression uniquely predicted substance use in adulthood, but the substances varied by subtype of aggression. Implications for findings are discussed. PMID- 20589226 TI - DIFFERENTIAL IMPACT OF WEST NILE VIRUS ON CALIFORNIA BIRDS. AB - The strain of West Nile virus (WNV) currently epidemic in North America contains a genetic mutation elevating its virulence in birds, especially species in the family Corvidae. Although dead American Crows (Corvus brachyrhynchos) have been the hallmark of the epidemic, the overall impact of WNV on North America's avifauna remains poorly understood and has not been addressed thoroughly in California. Here, we evaluate variation by species in the effect of WNV on California birds from 2004 to 2007 by using (1) seroprevalence in free-ranging birds, (2) percentage of carcasses of each species reported by the public that tested positive for WNV, (3) mortality determined from experimental infections, and (4) population declines detected by trend analysis of Breeding Bird Survey (BBS) data. Using Bayesian linear models, we extrapolate trends in BBS data from 1980-2003 (pre-WNV) to 2004-2007 (post-WNV). We attribute significant declines from expected abundance trends in areas supporting epiornitics to WNV transmission. We combine risk assessed from each of the four data sets to generate an overall score describing WNV risk by species. The susceptibility of California avifauna to WNV varies widely, with overall risk scores ranging from low for the refractory Rock Pigeon (Columba livia) through high for the susceptible American Crow. Other species at high risk include, in descending order, the House Finch (Carpodacus mexicanus), Black-crowned Night-Heron (Nycticorax nycticorax), Western Scrub-Jay (Aphelocoma californica), and Yellow billed Magpie (Pica nuttalli). Our analyses emphasize the importance of multiple data sources in assessing the effect of an invading pathogen. PMID- 20589227 TI - Rapid Optimization of SPECT Scatter Correction Using Model LROC Observers. AB - The problem we address is the optimization and comparison of window-based scatter correction (SC) methods in SPECT for maximum a posteriori reconstructions. While sophisticated reconstruction-based SC methods are available, the commonly used window-based SC methods are fast, easy to use, and perform reasonably well. Rather than subtracting a scatter estimate from the measured sinogram and then reconstructing, we use an ensemble approach and model the mean scatter sinogram in the likelihood function. This mean scatter sinogram estimate, computed from satellite window data, is itself inexact (noisy). Therefore two sources of noise, that due to Poisson noise of unscattered photons and that due to the model error in the scatter estimate, are propagated into the reconstruction. The optimization and comparison is driven by a figure of merit, the area under the LROC curve (ALROC) that gauges performance in a signal detection plus localization task. We use model observers to perform the task. This usually entails laborious generation of many sample reconstructions, but in this work, we instead develop a theoretical approach that allows one to rapidly compute ALROC given known information about the imaging system and the scatter correction scheme. A critical step in the theory approach is to predict additional (above that due to to the propagated Poisson noise of the primary photons) contributions to the reconstructed image covariance due to scatter (model error) noise. Simulations show that our theory method yields, for a range of search tolerances, LROC curves and ALROC values in close agreement to that obtained using model observer responses obtained from sample reconstruction methods. This opens the door to rapid comparison of different window-based SC methods and to optimizing the parameters (including window placement and size, scatter sinogram smoothing kernel) of the SC method. PMID- 20589228 TI - Under-estimation of Alcohol Consumption among Women At-risk for Drinking during Pregnancy. AB - This study adds to a growing literature showing that definitions for "standard drinks" are often difficult to conceptualize and that people often underestimate their actual drink sizes. As part of an intervention aimed at reducing negative neonatal and maternal outcomes, insured at-risk women were asked to identify the vessels from which they drank each of 6 beverages (n=266). We calculated differences between their actual and standard drink sizes. Additionally, differences were compared to those reported in an earlier study of uninsured inner city minority women that used identical vessels methodology. Over half of the spirits, fortified wine and malt liquor drinkers underestimated the actual number of ounces their drinks contained. Most spirits drinkers (90%) and approximately three-quarters of the wine and malt liquor drinkers drank larger than-standard drink sizes, with the median drink size 1.5 to 2.0 times larger than the standard size for those beverages. Heavier drinkers (>/=3 drinks per sitting) were more likely than lighter drinkers to underestimate their drink sizes. Findings were similar to those in the previous study using identical drink size measurements. Accurately assessing true drink sizes is underscored when the social, health and epidemiologic consequences associated with miscalculation are considered. PMID- 20589229 TI - Getting There from Here: Research on the Effects of Work-Family Initiatives on Work-Family Conflict and Business Outcomes. AB - Many employing organizations have adopted work-family policies, programs, and benefits. Yet managers in employing organizations simply do not know what organizational initiatives actually reduce work-family conflict and how these changes are likely to impact employees and the organization. We examine scholarship that addresses two broad questions: first, do work-family initiatives reduce employees' work-family conflict and/or improve work-family enrichment? Second, does reduced work-family conflict improve employees' work outcomes and, especially, business outcomes at the organizational level? We review over 150 peer-reviewed studies from a number of disciplines in order to summarize this rich literature and identify promising avenues for research and conceptualization. We propose a research agenda based on four primary conclusions: the need for more multi-level research, the necessity of an interdisciplinary approach, the benefits of longitudinal studies that employ quasi-experimental or experimental designs and the challenges of translating research into practice in effective ways. PMID- 20589231 TI - EFFECT OF FEEDING, EXERCISE AND GENOTYPE ON PLASMA 3-HYDROXYACYLCARNITINES IN CHILDREN WITH LCHAD DEFICIENCY. AB - Chronic complications observed in patients with long-chain 3-hydroxyacylCoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency may be mediated by the accumulation of 3-hydroxy fatty acids or 3-hydroxyacylcarnitines. To understand variation in metabolite accumulation, their concentrations were measured by tandem mass spectrometry before and after a mixed meal and moderate intensity exercise. Subjects who were homozygous or heterozygous for the common mutation (c.1528G>C) in the TFP alpha subunit (LCHAD deficiency) had significantly higher 3-hydroxyacylcarnitines than subjects with TFP deficiency. Feeding a mixed meal significantly suppressed and exercise significantly increased plasma 3-hydroxyacylcarnitines concentrations. PMID- 20589230 TI - Mesenchymal Stem Cells Sense Three Dimensional Type I Collagen through Discoidin Domain Receptor 1. AB - The extracellular matrix provides structural and organizational cues for tissue development and defines and maintains cellular phenotype during cell fate determination. Multipotent mesenchymal stem cells use this matrix to tightly regulate the balance between their differentiation potential and self-renewal in the native niche. When understood, the mechanisms that govern cell-matrix crosstalk during differentiation will allow for efficient engineering of natural and synthetic matrices to specifically direct and maintain stem cell phenotype. This work identifies the discoidin domain receptor 1 (DDR1), a collagen activated receptor tyrosine kinase, as a potential link through which stem cells sense and respond to the 3D organization of their extracellular matrix microenvironment. DDR1 is dependent upon both the structure and proteolytic state of its collagen ligand and is specifically expressed and localized in three dimensional type I collagen culture. Inhibition of DDR1 expression results in decreased osteogenic potential, increased cell spreading, stress fiber formation and ERK1/2 phosphorylation. Additionally, loss of DDR1 activity alters the cell-mediated organization of the naive type I collagen matrix. Taken together, these results demonstrate a role for DDR1 in the stem cell response to and interaction with three dimensional type I collagen. Dynamic changes in cell shape in 3D culture and the tuning of the local ECM microstructure, directs crosstalk between DDR1 and two dimensional mechanisms of osteogenesis that can alter their traditional roles. PMID- 20589232 TI - ? PMID- 20589233 TI - Dual-Energy Technique at Low Tube Voltages for Small Animal Imaging. AB - We investigate the feasibility of dual-energy method for image contrast enhancement in small animal studies using a low kV X-ray radiographic system. A robust method for X-ray spectrum estimation from transmission measurements, based on expectation-maximization (EM) method, is applied to an X-ray specimen radiographic system for dual energy imaging of a mouse. From transmission measurements of two known attenuators at two different X-ray tube voltages, the X ray energy spectra are reconstructed using the EM-based method. From the spectra information thus obtained, the transmission data for bone and soft tissue in terms of various thicknesses are generated. Two polynomial functions of transmission data are then sought for to fit the inverted thicknesses of bone and soft-tissue. Scatters in cone-beam projection data acquired at two X-ray energies were corrected. From the scatter-corrected data, a bone thickness map is separated from a soft-tissue thickness map by use of the polynomial functions. PMID- 20589234 TI - Informal social control of drinking in intimate relationships - a comparative analysis. AB - A number of studies have shown that pressure from others is an important element in decision making concerning entering treatment and that the pressure most often comes from one's partner. Is has also been found that, besides actual drinking habits, togetherness of drinking, i.e. proportion of drinking occasions spent together with partner, is reversely connected to pressure from partner to drink less. The purpose of this paper was to examine these relationships in a comparative perspective, using GENACIS survey data from 16 countries. The results confirmed that on both individual and aggregated level, there is a relationship between drinking and pressure from partner. There is more pressure reported in 'dry' cultures and heavy drinking individuals are more often the object than others - in all cultures studied. In only a few countries with rather different drinking culture, drinking together prevents the pressure, also when controlled for actual consumption. Except for Uganda and UK, men are generally more exposed to pressure to drink less exerted by their female partners and this cannot only be explained by the fact that they actually drink more. PMID- 20589235 TI - Identifying Basal Ganglia divisions in individuals using resting-state functional connectivity MRI. AB - Studies in non-human primates and humans reveal that discrete regions (henceforth, "divisions") in the basal ganglia are intricately interconnected with regions in the cerebral cortex. However, divisions within basal ganglia nuclei (e.g., within the caudate) are difficult to identify using structural MRI. Resting-state functional connectivity MRI (rs-fcMRI) can be used to identify putative cerebral cortical functional areas in humans (Cohen et al., 2008). Here, we determine whether rs-fcMRI can be used to identify divisions in individual human adult basal ganglia. Putative basal ganglia divisions were generated by assigning basal ganglia voxels to groups based on the similarity of whole-brain functional connectivity correlation maps using modularity optimization, a network analysis tool. We assessed the validity of this approach by examining the spatial contiguity and location of putative divisions and whether divisions' correlation maps were consistent with previously reported patterns of anatomical and functional connectivity. Spatially constrained divisions consistent with the dorsal caudate, ventral striatum, and dorsal caudal putamen could be identified in each subject. Further, correlation maps associated with putative divisions were consistent with their presumed connectivity. These findings suggest that, as in the cerebral cortex, subcortical divisions can be identified in individuals using rs-fcMRI. Developing and validating these methods should improve the study of brain structure and function, both typical and atypical, by allowing for more precise comparison across individuals. PMID- 20589236 TI - Nitric oxide enhances inhibitory synaptic transmission and neuronal excitability in Guinea-pig submucous plexus. AB - Varicosities immunoreactive for nitric oxide synthase (NOS) make synaptic connections with submucosal neurons in the guinea-pig small intestine, but the effects of nitric oxide (NO) on these neurons are unknown. We used intracellular recording to characterize effects of sodium nitroprusside (SNP, NO donor) and nitro-l-arginine (NOLA, NOS inhibitor), on inhibitory synaptic potentials (IPSPs), slow excitatory synaptic potentials (EPSPs) and action potential firing in submucosal neurons of guinea-pig ileum in vitro. Recordings were made from neurons with the characteristic IPSPs of non-cholinergic secretomotor neurons. SNP (100 muM) markedly enhanced IPSPs evoked by single stimuli applied to intermodal strands and IPSPs evoked by trains of 2-10 pulses (30 Hz). Both noradrenergic (idazoxan-sensitive) and non-adrenergic (idazoxan-insensitive) IPSPs were affected. SNP enhanced hyperpolarizations evoked by locally applied noradrenaline or somatostatin. SNP did not affect slow EPSPs evoked by single stimuli, but depressed slow EPSPs evoked by stimulus trains. NOLA (100 muM) depressed IPSPs evoked by one to three stimulus pulses and enhanced slow EPSPs evoked by trains of two to three stimuli (30 Hz). SNP also increased the number of action potentials and the duration of firing evoked by prolonged (500 or 1000 ms) depolarizing current pulses, but NOLA had no consistent effect on action potential firing. We conclude that neurally released NO acts post-synaptically to enhance IPSPs and depress slow EPSPs, but may enhance the intrinsic excitability of these neurons. Thus, NOS neurons may locally regulate several secretomotor pathways ending on common neurons. PMID- 20589237 TI - Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats. AB - Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg), arginine (0.6 g/kg), or their combined administration (0.6 g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects. PMID- 20589238 TI - Characterization of neural activity recorded from the descending tracts of the rat spinal cord. AB - A multi-electrode array (MEA) was implanted in the dorsolateral funiculus of the cervical spinal cord to record descending information during behavior in freely moving rats. Neural signals were characterized in terms of frequency and information content. Frequency analysis revealed components both at the range of local field potentials and multi-unit activity. Coherence between channels decreased steadily with inter-contact distance and frequency suggesting greater spatial selectivity for multi-unit activity compared to local field potentials. Principal component analysis (PCA) extracted multiple channels of neural activity with patterns that correlated to the behavior, indicating multiple dimensionality of the signals. Two different behaviors involving the forelimbs, face cleaning and food reaching, generated neural signals through distinctly different combination of neural channels, which suggested that these two behaviors could readily be differentiated from recordings. This preliminary data demonstrated that descending spinal cord signals recorded with MEAs can be used to extract multiple channels of command control information and potentially be utilized as a means of communication in high level spinal cord injury subjects. PMID- 20589239 TI - Invariance in visual object recognition requires training: a computational argument. AB - Visual object recognition is remarkably accurate and robust, yet its neurophysiological underpinnings are poorly understood. Single cells in brain regions thought to underlie object recognition code for many stimulus aspects, which poses a limit on their invariance. Combining the responses of multiple non invariant neurons via weighted linear summation offers an optimal decoding strategy, which may be able to achieve invariant object recognition. However, because object identification is essentially parameter optimization in this model, the characteristics of the identification task trained to perform are critically important. If this task does not require invariance, a neural population-code is inherently more selective but less tolerant than the single neurons constituting the population. Nevertheless, tolerance can be learned - provided that it is trained for - at the cost of selectivity. We argue that this model is an interesting null-hypothesis to compare behavioral results with and conclude that it may explain several experimental findings. PMID- 20589240 TI - Evaluation of the Consensus of Four Peptide Identification Algorithms for Tandem Mass Spectrometry Based Proteomics. AB - The availability of different scoring schemes and filter settings of protein database search algorithms has greatly expanded the number of search methods for identifying candidate peptides from MS/MS spectra. We have previously shown that consensus-based methods that combine three search algorithms yield higher sensitivity and specificity compared to the use of a single search engine (individual method). We hypothesized that union of four search engines (Sequest, Mascot, X!Tandem and Phenyx) can further enhance sensitivity and specificity. ROC plots were generated to measure the sensitivity and specificity of 5460 consensus methods derived from the same dataset. We found that Mascot outperformed individual methods for sensitivity and specificity, while Phenyx performed the worst. The union consensus methods generally produced much higher sensitivity, while the intersection consensus methods gave much higher specificity. The union methods from four search algorithms modestly improved sensitivity, but not specificity, compared to union methods that used three search engines. This suggests that a strategy based on specific combination of search algorithms, instead of merely 'as many search engines as possible', may be key strategy for success with peptide identification. Lastly, we provide strategies for optimizing sensitivity or specificity of peptide identification in MS/MS spectra for different user-specific conditions. PMID- 20589241 TI - Sentence comprehension: effectors and goals, self and others. An overview of experiments and implications for robotics. AB - According to theories referring to embodied and grounded cognition (Barsalou, 2008), language comprehension encompasses an embodied simulation of actions. The neural underpinnings of this simulation could be found in wide neural circuits that involve canonical and mirror neurons (Rizzolatti et al., 1996). In keeping with this view, we review behavioral and kinematic studies conducted in our lab which help characterize the relationship existing between language and the motor system. Overall, our results reveal that the simulation evoked during sentence comprehension is fine-grained, primarily in its sensitivity to the different effectors we employ to perform actions. In addition, they suggest that linguistic comprehension also relies on the representation of actions in terms of goals and of the chains of motor acts necessary to accomplish them. Finally, they indicate that these goals are modulated by both the object features the sentence refers to as well as by social aspects such as the characteristics of the agents implied by sentences. We will discuss the implications of these studies for embodied robotics. PMID- 20589242 TI - Striatal BOLD Response Reflects the Impact of Herd Information on Financial Decisions. AB - Like other species, humans are sensitive to the decisions and actions of conspecifics, which can lead to herd behavior and undesirable outcomes such as stock market bubbles and bank runs. However, how the brain processes this socially derived influence is only poorly understood. Using functional magnetic resonance imaging (fMRI), we scanned participants as they made decisions on whether to buy stocks after observing others' buying decisions. We demonstrate that activity in the ventral striatum, an area heavily implicated in reward processing, tracked the degree of influence on participants' decisions arising from the observation of other peoples' decisions. The signal did not track non human, non-social control decisions. These findings lend weight to the notion that the ventral striatum is involved in the processing of complex social aspects of decision making and identify a possible neural basis for herd behavior. PMID- 20589243 TI - How do we measure dental fear and what are we measuring anyway? AB - Dental anxiety shares similar characteristics with many clinical anxiety disorders, and this is especially the case with other specific fears and phobias. These often debilitating conditions comprise several different dimensions, including cognitive, emotional, behavioural and physiological components. In addition, dental anxiety and fear are associated with a range of aversive health consequences. A number of indices have been developed to measure dental anxiety and fear, but their sheer number is indicative of a continuing problem with delineating the concept of dental fear and anxiety and how these should best be measured. This paper addresses the widespread confusion in the use of relevant terminology and aims to trace and assess the theoretical underpinnings of a selection of the most widely used self-report measures. It is concluded that the most popular measures of dental anxiety and fear lack adequate or sufficiently explained theoretical foundations. This is of concern given that these scales, by their very nature, serve to define the concept they aim to measure. PMID- 20589244 TI - Overcoming barriers to tobacco cessation counselling in dental students. AB - PURPOSE: Tobacco use screening and brief intervention is recognised as an effective available preventive health service; yet, this service is still not routinely offered to dental patients by clinicians, despite dental schools generally providing some form of tobacco cessation counselling (TCC) by including it in their dental curriculum. A pilot study was therefore carried out to more clearly identify barriers that prevented the delivery of this service to tobacco using patients at the University of Pittsburgh School of Dental Medicine and educational initiatives that might overcome these barriers. MATERIALS AND METHODS: A survey of faculty and students asked participants to rank their knowledge, preparation and comfort levels in performing TCC as well as their belief as to the importance of such training in the dental curriculum. Six months following training and practice opportunities, surveys were again administered to participants. Each individual's pre- and post-TCC training surveys were reviewed and difference in response to each item was calculated. RESULTS: The results of the present study show that students feel more prepared, that the time required to provide TCC was less than anticipated and that training in TCC is an important part of dental education to a greater extent after the pilot study than before. CONCLUSIONS: TCC training and practice opportunities for clinical application were effective in this pilot study in improving students' attitudes towards cited barriers. PMID- 20589245 TI - Oral disease and social class in a random sample of five-year-old preschool children in a Brazilian city. AB - PURPOSE: The objective of the present study was to determine the association between oral disease, access to dental care and social class in a random sample of five-year-old preschool children in Belo Horizonte, Minas Gerais, Brazil. MATERIALS AND METHODS: A cross-sectional study was carried out on a sample of 551 five-year-old children who were randomly selected from preschools. Oral health status was assessed using the decayed, missing or filled teeth (dmft) index as well as the presence of visible plaque, gingivitis and supragingival calculus. Oral examinations were performed by two examiners (j > 0.80). The clinical outcome variables were dental caries, filled and missing teeth, dental pulp exposure due to caries, dental root fragment, visible plaque, gingivitis and supragingival calculus. Social class was assessed using the City Hall database. RESULTS: Children without caries represented 63.9% of the sample. Mean overall dmft was calculated to be 1.56, and the decayed teeth component was the highest in all of the social classes. Missing teeth, caries with pulp involvement and dental root fragment had higher proportions and the filled teeth component had the lowest proportion in children from the lowest social class. Visible dental plaque was present in 45.4% of the children. Except for the filled teeth component, all of the clinical outcome variables had a significant association with social class status (P < 0.001), regardless of child's gender. CONCLUSIONS: Oral disease in the primary dentition and access to dental treatment are affected by social and cultural factors. PMID- 20589246 TI - Adaptation of the Oral Aesthetic Subjective Impact Score (OASIS) questionnaire for perception of oral aesthetics in Brazil. AB - PURPOSE: The aim of the present study was to assess the cross-cultural adaptation and reliability and validity of the Oral Aesthetic Subjective Impact Score (OASIS) for the perception of oral aesthetics in Brazilian adolescents. MATERIALS AND METHODS: The cross-cultural adaptation was developed in agreement with internationally recommended methodology. The psychometric properties were assessed by application of the Brazilian version of the OASIS in 304 adolescents aged 13 to 19 years who were enrolled at two public schools and one private school in Tubarao, Brazil. The internal consistency of the instrument was measured using Cronbach's alpha. The reliability was estimated through stability and homogeneity, using the Intraclass Correlation Coefficient and the Bland Altman agreement. Validity was determined by comparing the OASIS-Brazil with the aesthetic component of the instrument Oral Impact on Daily Performance (OIDP) using the Spearman Rank Correlation Coefficient. RESULTS: The internal consistency obtained was 0.52. Inter-observer and intra-observer correlations were strong, 0.87 and 0.83, respectively. The correlation with the aesthetic part of OIDP was 0.44. CONCLUSIONS: The results showed that the process of cross cultural adaptation was successful and the adapted instrument showed good psychometric properties. PMID- 20589247 TI - Maroteaux-Lamy syndrome: orofacial features after treatment by bone marrow transplant. AB - PURPOSE: The objective of the present study was to emphasise the oral and dental findings of a male patient with the Maroteaux-Lamy syndrome who successfully underwent bone marrow transplantation (BMT) at the age of 22 months. CASE REPORT: A 15-year-old boy was referred to the Dentistry Division of the Catholic University of Brasilia, Brazil, for dental diagnosis. General characteristics of the Maroteaux-Lamy syndrome, such as a large head, a short neck, corneal opacity, an open mouth with macroglossia, enlargement of the skull and a long anteroposterior dimension, were observed. The patient had received the benefit of a BMT at an early stage. Therefore, characteristics were presented in a moderate form, except for the skeletal symptoms. DISCUSSION: Maroteaux-Lamy syndrome, also known as mucopolysaccharidosis type VI, is a lysosomal storage disorder that is caused by a deficiency of arylsulphatase B, which leads to an accumulation of dermatan sulphate in tissues and its increased excretion in urine. The deposition of mucopolysaccharides leads to a progressive disorder involving multiple organs. It is a rare condition that is inherited as an autosomal recessive trait. The characteristic features of this disease include retardation in growth, a large head, a short neck, corneal opacity, typical facies and spinal abnormalities. The main dental findings of this syndrome include gingival hyperplasia, hypertrophy of the maxillary alveolar ridge, macroglossia, unerupted dentition, malocclusions and dentigerous cyst-like follicles. BMT is a therapeutic treatment that is given to permanently replace any disorder caused due to the deficiency of enzymes in patients with storage diseases. PMID- 20589248 TI - Oral mucosal findings related to tobacco use and alcohol consumption: a study on Swiss army recruits involving self-reported and clinical data. AB - PURPOSE: The aim of the present study was to assess the oral mucosal health status of young male adults (aged 18 to 24 years) in Switzerland and to correlate their clinical findings with self-reported risk factors such as tobacco use and alcohol consumption. MATERIALS AND METHODS: Data on the oral health status of 615 Swiss Army recruits were collected using a standardised self-reported questionnaire, followed by an intraoral examination. Positive clinical findings were classified as (1) common conditions and anatomical variants, (2) reactive lesions, (3) benign tumour lesions and (4) premalignant lesions. The main locations of the oral mucosal findings were recorded on a topographical classification chart. Using correlational statistics, the findings were further associated with the known risk factors such as tobacco use and alcohol consumption. RESULTS: A total of 468 findings were diagnosed in 327 (53.17%) of the 615 subjects. In total, 445 findings (95.09%) were classified as common conditions, anatomical variants and reactive soft-tissue lesions. In the group of reactive soft-tissue lesions, there was a significantly higher percentage of smokers (P < 0.001) and subjects with a combination of smoking and alcohol consumption (P < 0.001). Eight lesions were clinically diagnosed as oral leukoplakias associated with smokeless tobacco. The prevalence of precursor lesions in the population examined was over 1%. CONCLUSIONS: Among young male adults in Switzerland, a significant number of oral mucosal lesions can be identified, which strongly correlate with tobacco use. To improve primary and secondary prevention, young adults should therefore be informed more extensively about the negative effects of tobacco use on oral health. PMID- 20589249 TI - Xerostomia and hyposalivation: a preliminary report of their prevalence and associated factors in Brazilian elderly diabetic patients. AB - PURPOSE: The objective of the present study was to determine the prevalence of xerostomia (dry mouth sensation) and hyposalivation in elderly type-2 diabetic individuals and to establish whether such conditions might be associated with their socioeconomic status and/or medical and oral health conditions. MATERIALS AND METHODS: The present cross-sectional study included 315 functionally independent elderly individuals, aged 60 years or above, residing in Natal, northeastern Brazil. A total of 52 subjects self-reported to be diabetic. The data on the subjects' health condition were collected using a questionnaire, performing a physical examination and sialometry (unstimulated and stimulated whole saliva flow rates), and the variables were subjected to descriptive statistics, chi-square and Student t test (a = 0.05). RESULTS: The prevalence of dry mouth was found to be 25%. Hyposalivation was found in 48% and 46% of the subjects in unstimulated and stimulated conditions, respectively. The only factor that was associated with xerostomia among the diabetics was workplace (P = 0.01), suggesting that elderly diabetics working at home might be less likely to have dry mouth than those working outside. No variable assessed was associated with hyposalivation, in either unstimulated or stimulated salivary flow. CONCLUSIONS: The prevalence of dry mouth and hyposalivation was high in elderly diabetics. Only at-home jobs were observed to be associated with dry mouth. There was no association between hyposalivation and the variables assessed, with regard to either unstimulated or stimulated saliva. Further studies, involving larger samples, are required to confirm the present findings. PMID- 20589250 TI - Is titanium tetrafluoride (TiF4) effective to prevent carious and erosive lesions? A review of the literature. AB - The present review summarises the effects of titanium tetrafluoride (TiF(4)) on the development and progression of carious and erosive lesions. The mode of action of TiF(4) is due to the formation of an acid-stable surface layer, which provides mechanical protection to the surface, and to an increased fluoride uptake, which might chemically reduce demineralisation of dental hard tissues. Most in vitro studies showed that TiF(4) is effective in reducing the formation of carious and erosive enamel and dentine lesions. Thereby, TiF(4) was equally or more effective than sodium fluoride (NaF), amine fluoride (AmF) or stannous fluoride (SnF(2)). While clinical data confirm the caries-preventive effect, clinical trials analysing the anti-erosive effect of TiF(4) are lacking. Few data available from in situ studies revealed conflicting results by showing either no effect or a beneficial effect of TiF(4) on enamel erosion. Even though research focused on TiF(4), there is also evidence to show that other metal fluorides, such as zirconium and hafnium tetrafluorides, affect enamel and dentine demineralisation. CONCLUSION: The potential of TiF(4) to prevent acid demineralisation requires further research to confirm the promising in vitro results obtained by in situ studies and clinical trials. PMID- 20589251 TI - Relationship between dietary patterns and dental caries in Sri Lankan adolescents. AB - PURPOSE: The aim of the present study was to assess the relationship between dental caries and dietary patterns in Sri Lankan adolescents. MATERIALS AND METHODS: The sample consisted of 1218, 15-year-olds who were selected from 48 schools in the Colombo district of Sri Lanka using a stratified cluster sampling technique. Data were collected by distributing questionnaires among both adolescents and their parents and by conducting an oral examination of all adolescents. A validated 13 foods/food groups food frequency questionnaire was used to obtain dietary information. RESULTS: Factor analysis extracted three dietary patterns from the 13 foods/food groups, and these patterns accounted for 41.44% of variation in the dietary intake. They were labelled as sweet, healthy and affluent dietary patterns. From the multiple logistic regression analysis, the sweet dietary pattern, household income and oral hygiene status emerged as significant predictors of dental caries. CONCLUSIONS: It was concluded that dietary pattern labelled as sweet emerged as a significant predictor of dental caries. PMID- 20589252 TI - Erosive potential of calcium-modified acidic candies in irradiated dry mouth patients. AB - PURPOSE: Patients who have received irradiation therapy on the head and neck area are known to suffer from reduced saliva flow and may therefore use acidic candies to relieve symptoms of dry mouth. However, such acidic candies have erosive potential even among healthy individuals. Therefore, the aim of the present study was to determine if calcium-modified acidic candies have reduced erosive potential in irradiated cancer patients. MATERIALS AND METHODS: Nineteen cancer patients (26 to 70 years) ipsilaterally irradiated on the head and neck area sucked control and calcium-modified acidic candies, while their whole saliva was collected into a closed system. The erosive potential of both candies was evaluated from saliva degree of saturation with respect to hydroxyapatite and by dissolution of hydroxyapatite (HAp) directly in candy-stimulated saliva. The results were compared to normative data that were previously obtained on 20 healthy test persons (21 to 29 years). RESULTS: No significant difference was obtained in the saliva flow rates between control and calcium-modified candy. However, the saliva became significantly less undersaturated with respect to HAp when sucking calcium-modified compared to control candy (P < 0.001) and more undersaturated for both candies in ipsilaterally irradiated cancer patients compared to normative data (P < 0.001). HAp dissolution was found to be significantly lower in patients sucking the modified candy compared to the control candy (P < 0.01) and, surprisingly, slightly lower in patients compared to normative data. CONCLUSIONS: Modified acidic candy with calcium has reduced erosive potential in patients irradiated on the head and neck area and could therefore be used as a favourable stimulant for relief of dry mouth. PMID- 20589253 TI - Influence of dental plaque on human enamel erosion: in situ / ex vivo study. AB - PURPOSE: The objective of the present in situ study was to evaluate the influence of dental plaque on human enamel erosion. MATERIALS AND METHODS: Thirteen volunteers wore acrylic palatal devices with four enamel specimens that were prepared from freshly extracted impacted human third permanent molars (4 x 4 mm), randomly selected and distributed into two vertical rows, corresponding to the following groups: GI, erosion of dental plaque-free samples, and GII, erosion of dental plaque-covered samples. For the formation of dental plaque, the specimens were placed 1 mm below the level of the appliance and covered with a plastic mesh to allow the accumulation of dental plaque. The palatal device was continuously worn by the volunteers for 14 consecutive days and then immersed in a soft drink (Coca-Cola, 150 ml) for 5 min, three times a day. Half of the surfaces of specimens were coated with nail varnish for profilometry tests. The study variables included the depth of enamel surface wear (profilometer, vertical ranges in lm) and the percentage of superficial microhardness change (%SMHC). Data were analysed using the t test (P < 0.05). RESULTS: The %SMHC and depth of enamel surface wear were significantly higher for GI (-87.82% +/- 3.66 and 4.70 lm +/- 1.65) than for GII (-13.79% +/- 4.22 and 0.14 lm +/- 0.03). CONCLUSIONS: It was concluded that the dental plaque formed in situ was able to protect the enamel surface against erosion by a cola soft drink, thus reducing the depth of enamel surface wear and the %SMHC. PMID- 20589254 TI - Recommendations by dental staff and use of toothpicks, dental floss and interdental brushes for approximal cleaning in an adult Swedish population. AB - PURPOSE: The aim of the present study was to evaluate the recommendations relating to the use of approximal cleaning aids given by dental hygienists and dentists, the self-care practices in a Swedish population and the ability to remove dental plaque. MATERIALS AND METHODS: A structured questionnaire was randomly distributed to 500 dental hygienists and 500 dentists and a similar questionnaire was distributed to 1000 randomly selected individuals, divided equally into the following age groups: 15 to 20, 21 to 40, 41 to 60 and > 60 years. A clinical examination evaluating the ability to remove approximal dental plaque was also carried out in a total of 60 regular users of approximal cleaning aids. Plaque was scored before and after cleaning with a toothpick, dental floss or an interdental brush. RESULTS: The response rate was 82%, 79% and 68% for the three groups. The results reveal that dental hygienists give more detailed information about a majority of the aspects that are related to the use of approximal cleaning aids compared with dentists (P < 0.01 or P < 0.001). The majority of the dental staff give recommendations to children and adolescents firstly to prevent dental caries and to older individuals to improve periodontal health. The use of different approximal cleaning aids on a daily basis varied with respect to age group (2% to 42%); dental floss dominated in the younger age groups and interdental brushes in the two oldest groups. In the clinical study, the largest plaque reduction was produced by the interdental brush (83%), followed by toothpicks (74%) and dental floss (73%). CONCLUSIONS: The present study indicated the importance of individual recommendations related to the use of approximal cleaning aids. PMID- 20589255 TI - Oral health attitudes and behaviour as predisposing factor for dental caries experience among health professional and other professional college students of India. AB - PURPOSE: The objective of the present study was to determine if there existed any difference between the attitudes and behaviour apart from dental caries status among health professional and other professional college students and to investigate the association of oral health attitudes and behaviour with dental caries. MATERIALS AND METHODS: The Hiroshima University-Dental Behaviour Inventory (HU-DBI) questionnaire was used to survey 1824 young student population of Udaipur, India. Dental caries status was evaluated using the World Health Organization caries diagnostic criteria for decayed, missing and filled teeth and surfaces (DMFT and DMFS, respectively). RESULTS: There was a significant difference (P < 0.05) between the health professional and other professional college students for various components of DMFT and DMFS. Moreover, health professional students reported significantly higher HU-DBI scores (better oral health attitudes and behaviour) than their comparative group. Untreated dental caries played a major contribution to the total DMFT scores in both the groups, with 0.23 and 0.28 mean decayed teeth reported among health professional and other professional students, respectively. Decayed and missing teeth components exhibited a significant negative correlation with HU-DBI scores, whereas a positive correlation existed with the filled teeth component. CONCLUSIONS: A difference existed between the health professional and other professional students with regard to caries experience, oral health attitudes and behaviour. DMF indices and their components were related to most of the oral health attitudes and behaviours. Decayed and missing teeth components were negatively related while filled component was positively related to HU-DBI score. PMID- 20589256 TI - In memoriam: Michel Degrange (1946-2010). PMID- 20589257 TI - Effects of different luting agents on bond strengths of fiber-reinforced composite posts to root canal dentin. AB - PURPOSE: To evaluate the bond strength between two fiber posts (FRC Postec and DT Light Post) and different composite resins following different surface treatments of the posts. MATERIALS AND METHODS: One hundred sixty extracted teeth were divided into sixteen groups (n = 10). After pretreatment of the post surface with (1) no treatment, (2) silanization, (3) sandblasting + silanization or (4) tribochemical coating, the posts were either luted with the resin cements provided by the manufacturers of the post system or with a core buildup material. Push-out tests were performed in a universal testing machine until the post segment was dislodged from the root section. Data were analyzed using ANOVA. Multiple comparisons were performed using Tukey's test. RESULTS: FRC Postec achieved significantly higher bond strengths than DT Light Post (p < 0.0001). Cementation with the core buildup material showed significantly higher bond strengths than the resin cement provided by the post manufacturers (p < 0.0001). CONCLUSION: Post type, type of surface treatment and type of resin cement were significant factors for bond strength. Luting with a core buildup material significantly increased the bond strengths. PMID- 20589258 TI - What you write will still be there. PMID- 20589259 TI - The problem of insufficient incisal display: a case presentation. AB - Enhancement of facial beauty is one of the primary elective goals of patients seeking dental care. Frequently, improvements in natural beauty can be expected to follow restoration of ideal relationships between the denture and the facial soft tissues. A very important feature in a youthful appearance is the incisal tooth display; the amount of maxillary incisal exposure gradually decreases with age, accompanied by a gradual increase in mandibular incisal exposure. However, this problem could be present in young people where the effects of age should not be apparent yet. There are some other factors that could accelerate this process. The present case illustrates the improvement and rejuvenation of an unesthetic young smile through restorative treatment. PMID- 20589260 TI - Development, in vitro testing, and clinical use of a 3.5 mm-diameter zirconia abutment. AB - The use of small-diameter implants is indicated when small missing teeth have to be replaced, especially in esthetic zones. Nevertheless, the small diameter can pose a limiting factor with respect to what materials can be used for the final crown. In most cases, full-ceramic crowns in combination with a ceramic abutment are usually the material of choice for final reconstructions. To date, based on mechanical considerations, a 3.5 mm implant diameter has been a contraindication for using ceramic abutments. The authors describe here the development, in vitro testing, and clinical use of a zirconium abutment with a 3.5 mm diameter. The advantages of this small-diameter zirconia abutment include a minimum platform height that offers optimal prosthetic flexibility, and an accurate transfer of the implant position on to the master model. Furthermore, a precise rotational orientation for single-tooth restorations, optimal mechanical stability, and optimal fatigue resistance can be achieved. The microgap is minimized and protection against overload is afforded. In the reported case, high patient satisfaction was achieved due also to an esthetically pleasing final result. PMID- 20589261 TI - Planning implants in the esthetic zone using a new implant 3D navigation system. AB - Guided implant surgery is becoming a clinical reality in the world of implant dentistry. In recent years, a Computer Aided Implantology Academy has even appeared, confirming the importance of this approach. Different navigation systems are available for the planning of surgical and prosthetic reconstructions. These systems make available to the surgeon and the prosthodontist the instruments necessary to plan a case and to work in a team to deliver a fixed restoration at the time of the surgical procedure in a minimally invasive and predictable way. This article evaluates the usefulness of this kind of planning in the esthetic zone, where perfection is mandatory. PMID- 20589262 TI - Full-mouth oral rehabilitation in a titanium allergy patient using zirconium oxide dental implants and zirconium oxide restorations. A case report from an ongoing clinical study. AB - This case report describes the full-mouth oral rehabilitation of a titanium allergic patient. The patient was a young female with amelogenesis imperfecta who had generalized massive tooth destruction. All teeth in the mouth were extracted and 15 CeraRoot acid-etched (ICE surface) implants were placed (seven implants in the maxilla and eight implants in the mandible). No immediate temporaries were placed. Temporaries were placed 3 months after surgery, and left in function for 2 months. The case was finally restored with zirconium oxide bridges and ceramic veneering (three bridges in the maxilla and another three in the mandible). The 3 year follow-up showed good stability of soft tissues and bone level. Zirconium oxide implants and restorations might be an alternative for the oral rehabilitation of titanium allergic patients. PMID- 20589263 TI - Photometric assessment of tooth color using commonly available software. AB - It would be expedient to develop a simple digital procedure for matching shade guides to teeth for dental restorations. It was hypothesized that precise and objective L*a*b* measurements could be performed on photographic images of teeth and shade guides using commonly available photo software. Tooth shade guide tabs, shaped like computer-generated posterior crowns, were used for color matching. Digital photographs were obtained of the vestibular surface of the tooth and the neighboring shade guide. Sections of the tooth and shade guide on the photograph were cropped and analyzed in Photoshop CS2. The precision error of the measurements was expressed as the coefficient of variation in percent. The effects of tolerance setting and number of measurements and analysts were evaluated. The difference in color was calculated as the DeltaE L*a*b*. The precision errors of the L*a*b* measurements with a tolerance setting of 6 pixels were better than 1.3%. There was no significant difference between one and five repeated measurements or between the measurements and the precision errors of two analysts. Color differences (DeltaE) between repeated measurements were below 0.5 units, thus reproducible and visually identical. DeltaE L*a*b* calculations were expedient for matching a particular color guide tab to the neighboring tooth. The color coordinates L*a*b* of teeth and shade guides can be calculated with a precision error of only 1.3%, using readily available software. A tolerance setting of 6 pixels is optimal and only one measurement and one analyst are necessary for objective and precise measurements. The described digital L*a*b* measurements on a photograph offer the dentist and the ceramist a simple, precise, and objective tool for matching tooth and shade guide. PMID- 20589264 TI - Clinical efficacy of a bleaching system based on hydrogen peroxide with or without light activation. AB - The objective of the present study was to assess the clinical efficacy of a dental bleaching system based on hydrogen peroxide with or without light activation. This randomized controlled trial evaluated the effect of the light when applied to the hydrogen peroxide by using a split-mouth design with 21 patients, with light activation in one hemi-arch but not in the other. The bleaching agent was QuickWhite 35% hydrogen peroxide and activation was conducted with a diode lamp (Luma Cool). The Classic Vita Guide was used to score tooth shades. Two consecutive applications of hydrogen peroxide were made to one hemi arch, each light-activated for 10 min. The other hemi-arch was then identically treated but without light activation. After removal of the bleaching agent, the shade was re-scored and the Wilcoxon signed ranks test was used to compare differences in tooth shade values. The bleaching treatment produced significant shade changes (P < 0.01) in both hemi-arches. After treatment, there were no statistically significant differences between light-treated and non-light-treated tooth types (central incisors, lateral incisors, and canines). However, taking central incisor, lateral incisor, and canine as a group, comparison between each hemi-arch showed a significant effect in the hemi-arch with light activation (P < 0.05). The use of diode light with a 35% hydrogen peroxide gel slightly improved the dental bleaching. PMID- 20589265 TI - Chemical complexity--supramolecular self-assembly of synthetic and biological building blocks in water. AB - Aqueous supramolecular chemistry, the non-covalent assembly of simple building blocks into higher ordered architectures in water has received much focus recently. Biological systems are able to form complex, and well-defined microstructures essential to cellular function, and supramolecular chemistry has demonstrated its utility in assembling molecules to form increasingly complex assemblies. This tutorial review will summarise non-covalent building blocks based on both synthetic and biological systems in an aqueous environment, emphasising the complexity of the assemblies formed. Examples of higher ordered assemblies will be highlighted, from supramolecular plastics to spider silks, towards more compartmentalised protocell precursors. PMID- 20589266 TI - Flexibility of ideal zeolite frameworks. AB - We explore the flexibility windows of the 194 presently-known zeolite frameworks. The flexibility window represents a range of densities within which an ideal zeolite framework is stress-free. Here, we consider the ideal zeolite to be an assembly of rigid corner-sharing perfect tetrahedra. The corner linkages between tetrahedra are hard-sphere oxygen atoms, which are presumed to act as freely rotating, force-free, spherical joints. All other inter-tetrahedral forces, such as coulomb interactions, are ignored. Thus, the flexibility window represents the null-space of the kinematic matrix that governs the allowable internal motions of the ideal zeolite framework. We show that almost all of the known aluminosilicate or aluminophosphate zeolites exhibit a flexibility window. Consequently, the presence of flexibility in a hypothetical framework topology promises to be a valuable indicator of synthetic feasibility. We describe computational methods for exploring the flexibility window, and discuss some of the exceptions to this flexibility rule. PMID- 20589267 TI - Recent developments in bio-inspired special wettability. AB - Nature is a school for scientists and engineers. After four and a half billion years of stringent evolution, some creatures in nature exhibit fascinating surface wettability. Biomimetics, mimicking nature for engineering solutions, provides a model for the development of functional surfaces with special wettability. Recently, bio-inspired special wetting surfaces have attracted wide scientific attention for both fundamental research and practical applications, which has become an increasingly hot research topic. This Critical Review summarizes the recent work in bio-inspired special wettability, with a focus on lotus leaf inspired self-cleaning surfaces, plants and insects inspired anisotropic superhydrophobic surfaces, mosquito eyes inspired superhydrophobic antifogging coatings, insects inspired superhydrophobic antireflection coatings, rose petals and gecko feet inspired high adhesive superhydrophobic surfaces, bio inspired water collecting surfaces, and superlyophobic surfaces, with particular focus on the last two years. The research prospects and directions of this rapidly developing field are also briefly addressed (159 references). PMID- 20589268 TI - Pressurized capillary electrochromatography with indirect amperometric detection for analysis of organophosphorus pesticide residues. AB - A new analytical method, pressurized capillary electrochromatography with indirect amperometric detection, has been developed for the determination of some non-electroactive organophosphorus pesticides (OPPs). When 0.1 mmol L(-1) of 3,4 dihydroxybenzylamine (DHBA) was added to the mobile phase containing 50% v/v of ACN and 50% v/v of MES buffer (10 mmol L(-1), pH 5.5), and +0.9 V (vs. Ag/AgCl) of working potential were used, maximal signal levels of analytes could be achieved. A separation voltage of +10 kV, a column pressure of 7.0 MPa and a pump flow rate of 0.05 mL min(-1) were selected as the other optimal conditions for separation of six OPPs, namely, dimethoate, methyl parathion, ethyl parathion, chlorpyrifos, chlorpyrifos-methyl, trichlorfon. The OPPs could be separated within 15 min and determined with the detection limits ranging from 0.008 to 0.2 mg/kg. Combining with a solid phase extraction procedure, mean recoveries between 78.9 and 87.2% for vegetable samples and from 81.4 to 98.6% for fruit samples were obtained. PMID- 20589269 TI - Antibody functionalized interdigitated micro-electrode (IDmicroE) based impedimetric cortisol biosensor. AB - This paper reports on an ultrasensitive, disposable, impedimetric biosensor for cortisol detection. C-Mab (a Cortisol specific monoclonal antibody) was covalently immobilized via amide bond on the surface of the interdigitated micro electrodes (IDmicroEs) functionalized with dithiobis(succinimidyl propionate) (DTSP) self-assembled monolayer (SAM). After C-Mab binding, unreacted active groups of DTSP were blocked using ethanolamine (EA) and glycine (Gly) mixture. The disposable sensors were exposed to solutions with different cortisol concentrations and a label-free electrochemical impedance (EIS) technique was used to determine the cortisol concentration. EIS results confirm that the EA Gly/C-Mab/DTSP/IDmicroE based biosensor exhibited the sensitivity of 2.855 kohms M(-1) and could accurately detect cortisol in the range of 1 pM to 10 nM in saliva. This work establishes the feasibility of using an impedance based biosensor as a disposable cortisol detector, capable of working with complex bodily fluids (e.g., saliva). The architecture enables the use of cortisol sensors at point-of-care. PMID- 20589275 TI - Graphene-based materials in electrochemistry. AB - Graphene, as the fundamental 2D carbon structure with exceptionally high crystal and electronic quality, has emerged as a rapidly rising star in the field of material science. Its sudden discovery in 2004 led to an explosion of interest in the study of graphene with respect to its unique physical, chemical, and mechanical properties, opening up a new research area for materials science and condensed-matter physics, and aiming for wide-ranging and diversified technological applications. In this critical review, we will describe recent advances in the development of graphene-based materials from the standpoint of electrochemistry. To begin with, electron transfer properties of graphene will be discussed, involving its unusual electronic structure, extraordinary electronic properties and fascinating electron transport. The next major section deals with the exciting progress related to graphene-based materials in electrochemistry since 2004, including electrochemical sensing, electrochemiluminescence, electrocatalysis, electrochemical energy conversion and FET devices. Finally, prospects and further developments in this exciting field of graphene-based materials are also suggested (224 references). PMID- 20589276 TI - Paracyclophanes as model compounds for strongly interacting pi-systems. Part 1. Pseudo-ortho-dihydroxy[2.2]paracyclophane. AB - In this work we describe a study of the ground and first excited state structures and energetics of a dihydroxy-derivative of [2.2]paracyclophane (PC), the pseudo ortho-dihydroxy[2.2]paracyclophane (o-DHPC), also termed 4,12 dihydroxy[2.2]paracyclophane. In order to understand the electronic interactions between the two pi-systems, the molecule is investigated by REMPI spectroscopy in a free jet and by quantum chemical calculations. REMPI-spectra of the cluster with one water molecule were also obtained and aid in the interpretation. The origin of the S(1) <-- S(0) transition lies at 31,483 cm(-1) (3.903 eV) for o DHPC and 31,263 cm(-1) (3.876 eV) for the o-DHPC x H(2)O cluster. An adiabatic excitation energy of 3.87 eV was computed for the S(1) <-- S(0) transition in o DHPC. The SCS-CC2 calculations deviate by less than 0.1 eV for the adiabatic excitation energies of PC, o-DHPC and the related aromatic molecules benzene and phenol. Considerable activity in a breathing vibration of 190 cm(-1) is found in the S(1) state of o-DHPC and o-DHPC x H(2)O, in agreement with the computed SCS CC2 value of 185 cm(-1). Further vibrations appear at +11 cm(-1) and +54 cm(-1) in o-DHPC. The computations and the available experimental data of the parent PC show that both PC and o-DHPC are rather flexible with respect to motions of the benzene moieties.While PC has a double minimum potential energy with respect to the torsional motion, a single-minimum structure is found for the ground state of o-DHPC. The geometry change upon excitation is less pronounced in o-DHPC as compared to PC. Two of the three possible rotational conformers of the OH groups were found to have similar energies, but spectral hole burning shows that the spectra are dominated by a single rotamer. PMID- 20589277 TI - Polycyclic aromatic hydrocarbon formation mechanism in the "particle phase". A theoretical study. AB - The synthesis of polycyclic aromatic hydrocarbons (PAHs) and the formation of soot platelets occur both during combustion at relatively low [O(2)], or under pyrolysis conditions. When the PAH size grows beyond the number of three-four condensed cycles, the partitioning of PAHs between the gas and particle phases favours the latter (i.e. adsorption). This study aims to assess which role the soot particle plays during PAH synthesis, in particular if catalytic or template effects of some sort can be exerted by the soot platelet on the adsorbed growing PAH-like radical. Our theoretical calculations indicate that chain elongation by ethyne addition cannot compete with cyclization when both can take place in the growing PAH-like radical, already in the gas phase. When it is adsorbed, cyclization is found to become easier than in the gas phase (more so, in terms of Gibbs free energy barriers, at higher temperatures), hinting at some sort of template effect, while chain elongation by ethyne addition becomes somewhat more difficult. The underlying soot platelet can assist (at lower temperatures) the formation of a larger aromatic hydrocarbon, by a final hydrogen abstraction from that endocyclic saturated carbon the newly formed cycle still bears. As an alternative (at higher temperature), a spontaneous hydrogen atom loss can take place. Finally, at rather low temperatures, the addition of the growing radical to the underlying soot platelet might occur and cause some reticulation, form more disordered structures, i.e. soot precursors instead of PAHs. PMID- 20589278 TI - Photoswitching tripodal single molecular tip for noncontact AFM measurements: synthesis, immobilization, and reversible configurational change on gold surface. AB - Tripodal molecules consisting of a tetrasubstituted adamantane with three phenylacetylene legs and a reversibly photoswitching apex were designed as "single molecular tips" for both chemical and topographical characterization of the substrate surface. By covalent attachment onto gold-coated AFM tips through three S-Au bonds, these rigid tripodal molecules are expected to act as sharp, robust, and stationary molecular tips whose configuration can be reversibly changed upon irradiation with UV or visible light. In this report, the full account of the syntheses of two photoswitching tripodal molecular tips, their immobilization onto Au(111) surfaces, and the detection of photoinduced configurational change on Au(111) surface by SPM measurements are documented. PMID- 20589279 TI - Domino gold-catalyzed rearrangement and fluorination of propargyl acetates. AB - A combination of IPrAuNTf(2) as catalyst in the presence of Selectfluor has been successfully used for the high yielding synthesis of alpha-fluoroenones via 1,3 acyloxy rearrangement of propargyl acetates followed by Csp(2)-F bond formation, likely involving a redox Au(I)/Au(III) catalytic cycle. PMID- 20589280 TI - Selective detection of Hg2+ in the microenvironment of double-stranded DNA with an intercalator crown-ether conjugate. AB - 9-[2-(1,4-Dioxa-7,13-dithia-10-azacyclopentadecyl)phenyl]amino benzo[b]quinolizinium enables the unambiguous fluorimetric and polarimetric detection of Hg(2+) in the close proximity of double-stranded nucleic acids without interfering background signals from the complexes of this compound with Hg(2+) or DNA alone. PMID- 20589281 TI - Ab initio anharmonic vibrational frequency predictions for linear proton-bound complexes OC-H(+)-CO and N(2)-H(+)-N(2). AB - Ab initio anharmonic transition frequencies are calculated for strongly coupled (i) asymmetric and (ii) symmetric proton stretching modes in the X-H(+)-X linear ionic hydrogen bonded complexes for OCHCO(+) and N(2)HN(2)(+). The optimized potential surface is calculated in these two coordinates for each molecular ion at CCSD(T)/aug-cc-pVnZ (n = 2-4) levels and extrapolated to the complete-basis set limit (CBS). Slices through both 2D surfaces reveal a relatively soft potential in the asymmetric proton stretching coordinate at near equilibrium geometries, which rapidly becomes a double minimum potential with increasing symmetric proton acceptor center of mass separation. Eigenvalues are obtained by solution of the 2D Schrodinger equation with potential/kinetic energy coupling explicity taken into account, converged in a distributed Gaussian basis set as a function of grid density. The asymmetric proton stretch fundamental frequency for N(2)HN(2)(+) is predicted at 848 cm(-1), with strong negative anharmonicity in the progression characteristic of a shallow "particle in a box" potential. The corresponding proton stretch fundamental for OCHCO(+) is anomalously low at 386 cm(-1), but with a strong alternation in the vibrational spacing due to the presence of a shallow D(infinityh) transition state barrier (Delta = 398 cm(-1)) between the two equivalent minimum geometries. Calculation of a 2D dipole moment surface and transition matrix elements reveals surprisingly strong combination and difference bands with appreciable intensity throughout the 300-1500 cm(-1) region. Corrected for zero point (DeltaZPE) and thermal vibrational excitation (DeltaE(vib)) at 300 K, the single and double dissociation energies in these complexes are in excellent agreement with thermochemical gas phase ion data. PMID- 20589282 TI - Novel biocompatible chitosan decorated single-walled carbon nanotubes (SWNTs) for biomedical applications: theoretical and experimental investigations. AB - Molecular mechanics and molecular dynamics simulations have been employed to characterise the interactions between SWNTs and biocompatible amphililic derivatives of chitosan, namely N-butyl-O-sulfate chitosan (NBSC), N-octyl-O sulfate chitosan (NOSC) and N-palmitoyl-O-sulfate chitosan (NPSC). The computational simulations have shown that the affinity of the polymer for the hydrophobic surface of the nanotubes depends on the length of the chitosan hydrophobic pendant chain. Longer chains have a higher flexibility and therefore a better ability to wrap around the nanotubes. To underpin the theoretical calculations, experimental studies revealed that NPSC exhibits highest affinity for SWNTs with up to 66.9 +/- 19.7% SWNTs stably suspended in an aqueous environment; this affinity was confirmed by the calculated binding energy of five polymer chains with a SWNT that was found to be -300.93 kcal mol(-1), the highest amongst the three polymers studied. Furthermore, the high value of cell viability after incubation with NPSC indicates that this is a good candidate for the preparation of biocompatible SWNTs dipersions that could be used in biomedical and pharmaceutical applications. PMID- 20589283 TI - Databases of virtual inorganic crystal structures and their applications. AB - Databases dedicated to predicted inorganic crystal structures are emerging fast. Possible applications are listed, from identification through the powder diffraction pattern fingerprint, leading to crystal structure determination before estimation of the cell parameters of newly synthesized real compounds, to the prediction of interesting properties of still unknown materials, allowing chemical synthesis efforts to concentrate on definite targets. The limitations of such approaches due, in some cases, to the incompleteness and poor quality of the predictions and to the lack of openly available efficient tools are discussed through examples. PMID- 20589284 TI - Non-contact acoustic cell trapping in disposable glass capillaries. AB - Non-contact trapping using acoustic standing waves has shown promising results in cell-based research lately. However, the devices demonstrated are normally fabricated using microfabrication or precision machining methods leading to a high unit cost. In e.g. clinical or forensic applications avoiding cross contamination, carryover or infection is of outmost importance. In these applications disposable devices are key elements, thus making the cost per unit a critical factor. A solution is presented here where low-cost off-the-shelf glass capillaries are used as resonators for standing wave trapping. Single-mode as well as multi-node trapping is demonstrated with an excellent agreement between simulated and experimentally found operation frequencies. Single particle trapping is verified at 7.53 MHz with a trapping force on a 10 microm particle of up to 1.27 nN. The non-contact trapping is proved using confocal microscopy. Finally, an application is presented where the capillary is used as a pipette for aspirating, trapping and dispensing red blood cells. PMID- 20589285 TI - Strong electrochemiluminescence based on electron transfer between Tris(2,2' bipyridine)ruthenium(III) and SnO NPs@MWCNTs. AB - Strong electrochemiluminescence signals caused by the highly effective electron transfer process between SnO nanoparticles-deposited multiwall carbon nanotubes (SnO NPs@MWCNTs) composite and Ru(bpy)(3)(3+) were observed. PMID- 20589286 TI - Nanomotor-based 'writing' of surface microstructures. AB - This communication demonstrates the 'writing' of surface microstructures by localized material deposition through the predefined movement of enzyme modified catalytic nanomotors. PMID- 20589287 TI - Construction of a quaternary carbon at the carbonyl carbon of the cyclohexane ring. AB - High S(N)2' selectivity in the allylic substitution of cyclohexylidene ethyl picolinates with copper reagents prepared from RMgBr and CuBr.Me(2)S was realized by addition of ZnX(2) (X = I, Br, Cl). Furthermore, ZnX(2) accelerated the reaction with the bulky iPr reagent. PMID- 20589288 TI - "Alive" dyes as fluorescent sensors: fluorophore, mechanism, receptor and images in living cells. AB - In this feature article, we report our recent progresses in fluorescent sensors of biological dyes from the viewpoint of supramolecular and bioorganic chemistry. For signalling fluorophores, we extended or created naphthalene-based ICT systems, e.g. amino-1,8-naphthalimides, amino-1,8-dicyanonaphthalenes and acenaphthopyrrol-9-carbonitriles. We also developed BODIPY derivatives with large Stokes shifts and high fluorescence quantum yields in polar solvents, and a rhodamine analogue working in strong competitive aqueous solution as well as its silaanthracene analogue with a bathochromic shift as large as 90 nm. For sensing mechanisms, we extended or developed the following methods to improve sensing: e.g. PET in a photogenerated electronic field, TICT promoted PET derived from aminoalkyl or piperazino aminonaphthalimides, and the translation/amplification effect of surfactant micelles or aggregation on fluorescent sensing. We also successfully designed deprotonation strengthened ICT, FRET-chemodosimeter sensing systems. For non-cyclic recognition receptors, naphthalimides with two or more side chains at their 4,5- or 3,4-positions, as a convenient and simple platform for ratiometric sensors, were created for the recognition of heavy and transition metallic cations; multi-armed polyamides with more side chains were innovated as a versatile platform for the sensing of metal ions with high affinity, selectivity and positive homotropic allosteric effects. We designed V-shape sensors of the bis(aminomethyl)pyridine receptor with two fluorophores to show high performance. Finally, the intracellular applications of the above sensors and dyes, e.g. imaging heavy and transition metal ions in cells, fluorescent marking of hypoxia of tumour cells, are also reviewed. PMID- 20589289 TI - Chemical dynamics of large amplitude motion. PMID- 20589290 TI - Causes of COD increases in Gwangyang Bay, South Korea. AB - Water quality, the carbon isotope ratio of particulate organic matter (POM) and sediment, and the nutrients limiting phytoplankton growth were investigated to determine the cause of organic matter increase and to determine an effective countermeasure for chemical oxygen demand (COD) increase in Gwangyang Bay, South Korea. The sources of most NO(3)-N and SiO(2)-Si entering Gwangyang Bay seem to be land-based, and the primary source of P appears to be industrial complex and/or domestic wastewater. The major cause of the COD increase in Gwangyang Bay was phytoplankton growth. Phytoplankton growth was limited by N at high salinity and by P at relatively low salinity. Phytoplankton growth was more limited by N in Gwangyang Bay than in similar bays because of a strong point source of P in Gwangyang Bay. In the rainy season, phytoplankton were able to massively grow in Gwangyang Bay after heavy rainfall events because of the high input of N from runoff, input of P and Si, and increasing sunlight after the rainy season. The peak chlorophyll a concentration observed in winter may have resulted from mixing N from the lower layer and because Eucampia grew well at low water temperatures. To improve COD levels in Gwangyang Bay, it is important to control the phytoplankton growth in the rainy season, particularly by limiting the input of NO(3)-N from outside the bay. PMID- 20589291 TI - Capillary driven low-cost V-groove microfluidic device with high sample transport efficiency. AB - In this study we investigate the liquid sample delivery speed and the efficiency of microfluidic channels for low-cost and low-volume diagnostic devices driven only by capillary forces. We select open, non-porous surface grooves with a V shaped cross section for modeling study and for sensor design. Our experimental data of liquid wicking in V-grooves show an excellent agreement with the theoretical data from the V-groove model of Rye et al. This agreement allows us to quantitatively analyze the liquid wicking speed in V-grooves. This analysis is used to generate data for the design of sensors. By combining V-groove channels and printable paper-like porous detection zones, microfluidic diagnostic sensors can be formed. Non-porous V-grooves can be fabricated easily on polymer film. Suitably long surface V-grooves allow short liquid transport time (<500 ms), thus reducing the evaporation loss of the sample during transport. Non-porous V grooves also significantly reduce chromatographic loss of the sample during transport, therefore increasing the sample delivering efficiency. Sensors of such design are capable of conducting semi-quantitative chemical and biochemical analysis (i.e. with a calibration curve) with less than 1000 nL of sample and indicator solution in total. PMID- 20589292 TI - Testing procedures for the determination of several biomarkers in different species, for environmental assessment of pollution. AB - Antioxidant defences are the primary mechanisms by which organisms compensate oxidative damage caused by contact with several types of substances prone to establish oxidative cycles. Biomarkers are one of the most useful tools to assess effects consequent to environmental exposure to a large number of xenobiotics. However, the use of biomarkers requires previous standardization of enzymatic protocols in order to guarantee accuracy and relevance of obtained results. This article describes standardized conditions for the use of several enzymatic biomarkers (oxidative stress: glutathione peroxidase, lipid peroxidation, glutathione reductase, glutathione-S-transferase and catalase; respiration: lactate dehydrogenase) for the evaluation of responses of specimens of Eisenia andrei, Pelophylax perezi (formerly Rana perezi) and Apodemus sylvaticus. Furthermore, we also present the normal values of activity for the given markers, for non-exposed organisms, that can serve as comparative indexes for subsequent studies. We conclude that these species are thus a suitable target to serve as sentinels in studies of environmental contamination by chemicals, which can lead to oxidative and physiological modifications. PMID- 20589294 TI - Fibrous aggregates from dinuclear zinc(II) salphen complexes. AB - Metal complexes composed of two zinc(II) salphen units that are bridged by a flexible hydrocarbon chain have been synthesized and characterized. Their self assembled supramolecular structures were studied with transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It was found that all of the complexes displayed nanofibrillar morphology and that the surface texture and diameter can be altered by the addition of 4,4'-bipyridine and hydrophobic effects, respectively. PMID- 20589293 TI - Nitrogen-bound diazeniumdiolated amidines. AB - In contrast to amidines bearing ionizable alpha-CH bonds, which react with nitric oxide (NO) to add diazeniumdiolate groups at their alpha-carbons, benzamidine forms an N-bound diazeniumdiolate that can be further derivatized at the other amidine nitrogen and/or the terminal oxygen to form caged NO compounds as potential NO prodrugs. PMID- 20589298 TI - Persistence length of DNA molecules confined in nanochannels. AB - The influence of confinement on the persistence length of dsDNA molecules under a high ionic strength environment was explored by coarse-grained Monte Carlo simulations in channels of different profiles. It was found that under confinement three definitions of the persistence length of DNA molecules were not equivalent and represented different properties. In case of the global quantities, the projection and the WLC persistence lengths, the apparent values up to several hundred nanometres are observed for DNA confined in narrow channels. The orientational correlation function cos theta(s) of confined DNA shows a complex pattern, distinctive for semiflexible polymers. At weak and moderate confinements the function cos theta(s) suggests an unexpected increase in the apparent DNA flexibility. The orientational persistence length computed from the initial slope of the function cos theta(s) mirrors only short-scale correlations and gives the value close to the intrinsic persistence length of DNA. The simulation data of direct relevance to experimental studies of DNA in microfluidic devices are compared with analytical theories for stiff chains. PMID- 20589299 TI - Synthesis and characterization of neutral and anionic carbonyl derivatives of palladium(II). AB - The action of CO on the solvento-complexes cis-[PdR2(thf)2] [R = C6F5 (1), C6Cl5 (2)] at low temperature gives cis-[PdR2(CO)2] [R = C6F5 (3), C6Cl5 (4)] in good yield by simple replacement of the highly labile thf molecules. These are rare cases of Pd(II) dicarbonyl compounds, whose characterization relies on spectroscopic and analytic data. The crystal structure of the square-planar platinum homologue cis-[Pt(C6Cl5)2(CO)2] is also presented. CO can split the double bridging-system in the dinuclear species [{PdR2}2(mu-X)2]2- giving the homologous series of anionic monocarbonyl Pd(II) derivatives with formula [cis PdR2X(CO)]- (5-10: R = C6F5, C6Cl5; X = Cl, Br, I), which were isolated (except for the R = C6F5 and X = I) and suitably characterized. Characterization includes the crystal and molecular structure of [PPh3Me][cis-Pd(C6F5)2Br(CO)] (6'). The anionic species [NBu4][cis-Pd(C6F5)2Cl(CO)] (5) reacts with neutral cis [Pd(C6F5)2(CO)2] (3) under CO extrusion, affording the dinuclear derivative [NBu4][{Pd(C6F5)2(CO)}2(mu-Cl)] (11), which contains a single unsupported halide bridge (X-ray diffraction). Complex 11 can be considered as modelling a possible intermediate step in intermolecular CO substitution reactions that are easily undergone by Pd(II) halo carbonyl species. PMID- 20589300 TI - Ciguatoxin: developing the methodology for total synthesis. PMID- 20589301 TI - Tetrabutyl titanate-controlled polymerization of epsilon-caprolactone at ambient temperature. AB - A low cost and environmentally benign process for tetrabutyl titanate-controlled ring-opening polymerization of epsilon-caprolactone at ambient temperature of 10 40 degrees C is introduced affording poly(epsilon-caprolactone) with pre-designed molecular weights and narrow molecular weight distribution. PMID- 20589304 TI - Iridium(III) luminophores as energy donors for sensitised emission from lanthanides in the visible and near-infrared regions. AB - Luminescent iridium(iii) complex units bearing pendant 2,2'-bipyridyl-type binding sites can be used to generate Ir/Ln dyads in which the Ir(iii) luminophore acts as an energy donor to the lanthanide by the Dexter mechanism, generating sensitised emission in the visible (from Eu) or near-infrared (Nd, Yb) regions. PMID- 20589307 TI - Luminescence enhancement of europium(III) originating from self-assembled supramolecular hydrogels. AB - Luminescence enhancement of the rare-earth ion Eu(III) in supramolecular hydrogels formed by self-assembly of the hydrogelator N,N-dibenzoyl-L-cystine (DBC) was observed by fluorescent optical microscopy and steady-state luminescence. The spectra of varying temperature luminescence showed that luminescence intensities of Eu(III) in DBC gels decreased with an increase of temperature and a dramatic decrease observed in the range 60-70 degrees C, which can be ascribed to the dissociation of DBC aggregates. This implied that the luminescence enhancement of Eu(III) in supramolecular hydrogels is related to the self-assembled DBC. The morphology of DBC aggregates in the presence of Eu(III) shows highly entangled and thin fibrillar aggregates compared with less entangled and thick aggregates in the absence of Eu(III). The phase transition temperature (T(SG)) of DBC gels increased with an increase of Eu(III) concentration. This suggests that interaction occurs between Eu(III) and DBC aggregates. The UV and FT-IR spectra of the DBC gels in the presence of Eu(III) indicated the formation of complexation between Eu(III) and oxygen atoms of DBC aggregates. The results reveal the mechanism of the luminescence enhancement of Eu(III) in supramolecular hydrogels, which most likely involve the interaction between Eu(III) and DBC aggregates. PMID- 20589308 TI - De novo synthesis and lectin binding studies of unsaturated carba-pyranoses. AB - Starting from branched para-benzoquinones a practical and highly flexible route is described for the preparation of unsaturated carbapyranoses. The potential of the synthesized galactose analogues to act as competitive inhibitors in lectin carbohydrate interactions is investigated by means of Surface Plasmon Resonance (SPR) Spectroscopy. PMID- 20589310 TI - Oxidative addition of the bismuth-chloride bond: synthesis and structure of trans [PtCl(PCy3)2{BiCl2}]. AB - The synthesis and full characterisation of trans-[PtCl(PCy(3))(2){BiCl(2)}] is reported via the oxidative addition of the bismuth-chloride bond across [Pt(PCy(3))(2)]; this represents the first instance of such an oxidative addition reaction to be undertaken by a bismuth halide bond. PMID- 20589309 TI - An engineered riboswitch as a potential gene-regulatory platform for reducing antibacterial drug resistance. AB - Synthetic riboswitch containing aptamer is constructed in E. coli to regulate the expression of beta-lactamase through small molecule-aptamer interactions, which sharply reduces the antibiotic resistance of the engineered bacteria. PMID- 20589311 TI - Synergism between factor XII -4C>T and factor XIII Val34Leu polymorphisms in fibrinolytic therapy in acute myocardial infarction. PMID- 20589312 TI - BMS-593214, an active site-directed factor VIIa inhibitor: enzyme kinetics, antithrombotic and antihaemostatic studies. AB - Factor (F) VIIa in association with tissue factor (TF) is the primary in vivo initiator of blood coagulation and activates FX and FIX to generate thrombin, which plays a key role in the pathogenesis of thrombosis. We evaluated the enzyme kinetics, antithrombotic and antihaemostatic properties of BMS-593214, an active site, direct FVIIa inhibitor. Studies were conducted in enzymatic assays, and in anesthetised rabbit models of electrically-induced carotid arterial thrombosis (AT), thread-induced vena cava venous thrombosis (VT) and cuticle bleeding time (BT). Antithrombotic efficacy of BMS-593214 given intravenously was evaluated for both the prevention and treatment of AT and VT. BMS-593214 displayed direct, competitive inhibition of human FVIIa in the hydrolysis of a tripeptide substrate with Ki of 5 nM. However, it acted as a noncompetitive inhibitor of the activation of the physiological substrate FX by TF/VIIa with Ki of 9.3 nM. BMS 593214 showed selectivity for FVIIa and exhibited species differences in TF-FVIIa dependent anticoagulation with similar potency in human and rabbit plasma. BMS 593214 was efficacious in the prevention and treatment models of AT and VT with ED50 values of 1.1 to 3.1 mg/kg. Furthermore, BMS-593214 exhibited a wide therapeutic window with respect to BT. These results suggest that inhibition of FVIIa with small-molecule active-site inhibitors represents a promising antithrombotic approach for the development of new therapies for the prevention and treatment of AT and VT. PMID- 20589313 TI - A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease. AB - Desmopressin aggravates thrombocytopenia in type 2B von Willebrand disease (VWF type 2B) by release of large and hyper-adhesive von Willebrand Factor (VWF) multimers. This pilot study investigated whether the anti-VWF aptamer ARC1779 can prevent desmopressin-induced thrombocytopenia and interferes with the excessive VWF turnover in patients with VWF type 2B. Concentration effect curves of ARC1779 were established for five patients in vitro and two patients with VWF type 2B were treated by infusion of ARC1779, desmopressin, or their combination in a randomised, controlled, double-blind design. ARC1779 concentrations in the range of 1-3 microg/ml blocked free A1 domain binding sites by 90% in vitro. In vivo, desmopressin alone induced a profound (-90%) drop in platelet counts in one of the patients. ARC1779 (4-5 microg/ml) completely inhibited VWF A1 domains and prevented this desmopressin-induced platelet drop. Desmopressin alone increased VWF antigen two- to three-fold, accompanied by concordant changes in VWF Ristocetin cofactor activity (RCo) and coagulation factor VIII activity. ARC1779 substantially enhanced the desmopressin-induced maximal increase in these parameters, and improved multimer patterns. No treatment related adverse events were observed and no bleeding occurred despite marked thrombocytopenia. These data provide first proof of concept in humans and evidence that ARC1779 is a potent inhibitor of VWF. ARC1779 prevented the rapid consumption of VWF multimers together with agglutinated platelets that occurred in response to desmopressin challenge in patients with VWD type 2B. PMID- 20589314 TI - Comparison of plasma-derived and recombinant von Willebrand factor by atomic force microscopy. AB - Human plasma protein von Willebrand factor (VWF) is composed of a series of multimers with molecular weights ranging from 600 to 20,000 kDa or even more. Plasma-derived VWF (pdVWF) and recombinant VWF (rVWF) differ in that the ultra large molecular weight multimer portion present in rVWF is usually missing in pdVWF due to partial cleavage of VWF by the plasma protease ADAMTS13. Here, tapping mode atomic force microscopy (TM-AFM) was used to visualise the shape and size of rVWF and pdVWF. The morphology of the variants of VWF was comparable, containing both globular and stretched domains. Mean chain lengths of the filaments and diameters of the core globular domains were determined and analysed on a statistical basis. About 72% of the pdVWF molecules and 70% of the rVWF molecules were 100-300 nm long. The portion of very long molecules (>300 nm) was only slightly greater in rVWF than in pdVWF (20% vs. 18%). The diameters of the globular core structures were in the range of 12 to 30 nm for both types of VWF. Inspection of a purified rVWF dimer revealed a similar range for the globular domain (14-32 nm). Finally, we demonstrate a dramatic conformational change for rVWF upon exposure to high shear stress, as has been reported for pdVWF. Our TM AFM data show that the overall structure of rVWF is similar to that of pdVWF and that rVWF will extend its conformation under shear stress, which is required to exert its function in primary haemostasis. PMID- 20589315 TI - Validation of a novel ELISA-based VASP whole blood assay to measure P2Y12-ADP receptor activity. PMID- 20589316 TI - Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: comparison with direct inhibitors of factor VIIa, XIa and thrombin. AB - Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development. This study evaluated the in vitro effect of apixaban on human platelet aggregation induced by thrombin derived via the extrinsic pathway. Direct inhibitors of FXa (rivaroxaban), FVIIa (BMS-593214), thrombin (dabigatran, argatroban) and FXIa (BMS-262084) were included for comparison. Citrated human platelets-rich plasma (PRP) was treated with 50 mg/ml corn trypsin inhibitor (to block the contact factor pathway) and 3 mM H-Gly-Pro Arg-Pro-OH-AcOH (to prevent fibrin polymerisation). Human tissue factor (TF) (Innovin; dilution 1:1,000 to 1:1,500) plus 7.5 mM CaCl2 was added to PRP pre incubated with vehicle or increasing concentrations of inhibitors. The TF-induced platelet aggregation was measured by optical aggregometry. TF produced 85 +/- 3% aggregation of human platelets in the vehicle-treated group (n=10). Apixaban and other factor inhibitors, except the FXIa inhibitor, inhibited TF-induced platelet aggregation with IC50 (nM) values as follows: 4 +/- 1 (apixaban), 8 +/- 2 (rivaroxaban), 13 +/- 1 (BMS-593214), 46 +/- 1 (dabigatran) and 79 +/- 1 (argatroban). BMS-262084 (IC50 = 2.8 nM vs. human FXIa) had no effect on TF induced platelet aggregation at 10 microM. These inhibitors at 10 microM had no effect on platelet aggregation induced by ADP and collagen, as expected from their mechanism of action. This study demonstrates that inhibition of thrombin generation by blocking upstream proteases (FVIIa and FXa) in the blood coagulation cascade is as effective as direct thrombin inhibition in preventing TF-induced platelet aggregation. Under these experimental conditions, a FXIa inhibitor did not prevent TF-induced platelet aggregation. PMID- 20589317 TI - Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study. AB - Edoxaban is a new oral direct factor Xa inhibitor. The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism (VTE) in patients undergoing elective total hip replacement. A total of 903 patients were randomised to oral edoxaban 15, 30, 60 or 90 mg once daily or subcutaneous dalteparin once daily (initial dose 2,500 IU, subsequent doses 5,000 IU). Both drugs were begun 6-8 hours postoperatively and continued for 7-10 days, when bilateral venography was performed. The primary efficacy endpoint was the incidence of total VTE, which included proximal and/or distal deep-vein thrombosis (DVT) by venography or symptomatic, objectively confirmed DVT or pulmonary embolism during the treatment period. The primary safety outcome was the incidence of the composite of major and clinically relevant non-major bleeding. All venograms and bleeding events were reviewed by a central independent adjudication committee blinded as to treatment allocation. Of the 903 patients randomised, 776 were evaluable for the primary efficacy analysis. The incidences of VTE were 28.2%, 21.2%, 15.2%, and 10.6% in patients receiving edoxaban 15, 30, 60 and 90 mg, respectively, compared with 43.8% in the dalteparin group (p<0.005 ). There was a statistically significant (p<0.001) dose response for efficacy across the edoxaban dose groups for total VTE and for major VTE. The incidence of clinically relevant bleeding was low and similar across the groups. Oral edoxaban once daily is effective for preventing VTE after total hip replacement. PMID- 20589318 TI - Covert brain ischaemia in splenectomised adults with thalassemia intermedia: An emerging entity. PMID- 20589319 TI - A C-terminal amino acid substitution in the gamma-chain caused by a novel heterozygous frameshift mutation (Fibrinogen Matsumoto VII) results in hypofibrinogenaemia. AB - We found a novel hypofibrinogenemia designated as Matsumoto VII (M-VII), which is caused by a heterozygous nucleotide deletion at position g.7651 in FGG and a subsequent frameshift mutation in codon 387 of the gamma-chain. This frameshift results in 25 amino acid substitutions, late termination of translation with elongation by 15 amino acids, and the introduction of a canonical glycosylation site. Western blot analysis of the patient's plasma fibrinogen visualised with anti-gamma-chain antibody revealed the presence of two extra bands. To identify the extra bands and determine which of the above-mentioned alterations caused the assembly and/or secretion defects in the patient, 11 variant vectors that introduced mutations into the cDNA of the gamma-chain or gamma'-chain were transfected into Chinese hamster ovary cells. In vitro expression of transfectants containing gammaDelta7651A and gammaDelta7651A/399T (gammaDelta7651A with an amino acid substitution of 399Asn by Thr and a variant lacking the canonical glycosylation site) demonstrated a reduction in secretion to approximately 20% of the level seen in the transfectants carrying the normal gamma-chain. Furthermore, results from other transfectants demonstrated that eight aberrant residues between 391 and 398 of the M-VII variant, rather than the 15 amino acid extension or the additional glycosylation, are responsible for the reduced levels of assembly and secretion of M-VII variant fibrinogen. Finally, the results of this study and our previous reports demonstrate that the fibrinogen gamma-chain C-terminal tail (388-411) is not necessary for protein assembly or secretion, but the aberrant amino acid sequence observed in the M-VII variant (especially 391-398) disturbs these functions. PMID- 20589320 TI - mRNA levels of CD31, CD144, CD146 and von Willebrand factor do not serve as surrogate markers for circulating endothelial cells. AB - Circulating endothelial cells (CEC) are considered a promising marker to determine the extent of vascular damage. However, currently available and validated CEC enumeration assays are laborious, time consuming and costly, which limits their clinical utility. Here, we evaluated the feasibility of quantifying mRNA levels of the endothelium-associated markers CD31, CD144, CD146 and von Willebrand factor (vWf) in peripheral blood (PB) of healthy donors, patients, and human umbilical veins by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and their use as surrogate markers for CEC. Whole blood samples and CD146+ cell-enriched fractions were assessed for mRNA and protein expression of CD31, CD144, CD146 and vWf by RT-PCR and flow cytometry, respectively. We showed the feasibility to detect endothelial mRNA isolated from HUVEC numbers as low as 10. However, no endothelial mRNA could be measure in whole blood samples, and only low levels of CD31 and CD146 mRNA were detected in suspensions of isolated CEC with numbers up to 4,450 CEC per sample. We conclude that mRNA levels of CD31, CD144, CD146 and vWf in whole blood as detected by real time RT PCR cannot be used as biomarkers for end-stage endothelial cells such as CEC. PMID- 20589321 TI - Strenuous exercise promotes shear-induced thrombin generation by increasing the shedding of procoagulant microparticles from platelets. AB - Vigorous exercise increases the risk of vascular thrombotic events. Shear stress enhances the shedding of procoagulant microparticles from platelets, and triggers thrombin generation (TG) in blood. This study explicates the manner in which strenuous exercise affects platelet-derived microparticles (PDMP) release and PDMP-mediated TG under various physio-pathological shear flows. Twenty-four sedentary healthy men performed a graded exercise test (up to VO2max) on a bicycle ergometer. At rest, immediately after and 2 hours after exercise, platelet-rich plasma (PRP) was exposed in a cone-and-plate viscometer to imitate static (0 dyne/cm2), physiological low (LS, 10 dyne/cm2) and pathological high (HS, 100 dyne/cm2) shear stresses ex vivo. The PDMP characteristics and dynamic TG were measured by two-colour flow cytometry and calibrated, automatic thrombinography, respectively. The results demonstrated that there is an increased level of total PDMP together with elevated peak height and rate of TG in PRP in response to both LS and HS conditions. Furthermore, HS, but not LS, promoted the binding of FV/Va or FVIII and the exposure of phosphatidylserine (PS) on platelets. Application of HS after strenuous exercise increased the factor (F)V/Va-/FVIII-/tissue factor-rich and PS-exposing PDMP counts, enhanced the PDMP-promoted peak height and rate of TG, as well as increased the ability of FV/Va or FVIII to bind to PDMP or platelets. However, the enhancement of HS induced procoagulant activity reversed to the pre-exercise status 2 hours following this exercise. Therefore, we conclude that strenuous exercise modestly contributes to the acceleration of shear-induced TG by increasing the release of procoagulant microparticles from platelets. PMID- 20589322 TI - Thrombogenesis with continuous blood flow in the inferior vena cava. A novel mouse model. AB - Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (DCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 muAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 muAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in DCT vs. WT (WT/PAI-1: p=0.003, WT/DCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow. PMID- 20589323 TI - In vitro effects of human neutrophil cathepsin G on thrombin generation: Both acceleration and decreased potential. AB - Cathepsin G (Cath G), a serine-protease found in neutrophils, has been reported to have effects that could either facilitate or impede coagulation. Thrombin generation (CAT method) was chosen to study its overall effect on the process, at a plasma concentration (240 nM) observed after neutrophil activation. Coagulation was triggered by tissue factor in the presence of platelets or phospholipid vesicles. To help identify potential targets of Cath G, plasma depleted of clotting factors or of inhibitors was used. Cath G induced a puzzling combination of two diverging effects of varying intensities depending on the phospholipid surface provided: accelerating the process under the three conditions (shortened clotting time by up to 30%), and impeding the process during the same thrombin generation time-course since thrombin peak and ETP (total thrombin potential) were decreased, up to 45% and 12%, respectively, suggestive of deficient prothrombinase. This is consistent with Cath G working on at least two targets in the coagulation cascade. Our data indicate that coagulation acceleration can be attributed neither to platelet activation and nor to activation of a clotting factor. When TFPI (tissue factor pathway inhibitor) was absent, no effect on lag time was observed and the anticoagulant activity of TFPI was decreased in the presence of Cath G. Consistent with the literature and the hypothesis of deficient prothrombinase, experiments using Russel's Viper Venom indicate that the anticoagulant effect can be attributed to a deleterious effect on factor V. The clinical relevance of these findings deserves to be studied. PMID- 20589324 TI - Integrins on neutrophils are dispensable for migration into three-dimensional fibrin gels. AB - The innate immune system and the blood haemostasis system function cooperatively in many pathological conditions such as acute respiratory distress syndrome, deep venous thrombosis, ischaemia/reperfusion injury and cardiovascular disease. Infiltration of neutrophils into thrombotic substrates such as fibrin clots supports fibrinolysis, tissue damage and inflammation. Despite the importance of integrins in neutrophil attachment to fibrin-coated surfaces under flow conditions, little is known about their role in migration processes in shear free two-dimensional (2D) and three-dimensional (3D) fibrin(ogen) environments. Therefore, the present study was designed to study the role of functional integrins in mediating neutrophil migration on and in fibrin matrices. Time lapse video sequences of neutrophil chemokinesis and chemotaxis were made under conditions of active- or non-active integrins. Interestingly, migration of neutrophils on 2D fibrinogen coated surfaces and 3D fibrin matrices is independent of integrins as the response is not sensitive to alphaM-(CD11b) and beta2-(CD18) blocking antibodies and/or chelation of Ca2+ and Mg2+ by EDTA in bivalent ion-free buffers. The blocking integrin antibodies were shown to be functionally active in regular adhesion assays. Our study shows that integrins are dispensable for migration on 2D and in 3D fibrin matrices, both when neutrophils enter into the fibrin matrix and when captured in the matrix. PMID- 20589325 TI - [The moral of Tartuffe?]. PMID- 20589326 TI - Performance of the Ogawa-Kudoh method for isolation of mycobacteria in a laboratory with large-scale workload. AB - In Uruguay (population 3,323,906; notified tuberculosis incidence 18.4/100,000), virtually all 30,000 samples yearly collected for mycobacterial culture countrywide are processed in a central laboratory. An average of 110 samples are routinely shipped daily and maintained 48-96 hours at room temperature until cultured on Lowenstein-Jensen slants using the standard NALC-NaOH decontamination procedure. The much simpler Kudoh decontamination/culture method -swab and Ogawa (acidified) medium- was compared with NALC-NaOH/Lowenstein-Jensen for isolation of mycobacteria from sputa under routine conditions. To this aim, 784 sputum samples were cultured by both methods in the summertime. Gross agreement was 0.99, kappa: 1. Kudoh performance was as follows: sensitivity 100% and accuracy 98.9%. Assays using a modified culture medium, different decontamination times and NaOH concentrations showed the versatility of this procedure. Thus, the Kudoh method is suitable for culturing mycobacteria from naturally contaminated samples even when processing is deferred two to four days after collection. PMID- 20589327 TI - [CAP59 gene amplification in Cryptococcus neoformans and Cryptococcus gattii directly from a yeast suspension]. AB - Cryptococcus is an encapsulated yeast of class Basidiomycetes, etiologic agent of cryptococcosis. Cryptococcosis is one of the most common opportunistic infections in immunosuppressed patients, although it can affect immunocompetent individuals. In recent years, the identification of medically important fungal species has been achieved through the amplification of specific regions or genes of fungal DNA by polymerase chain reaction (PCR). The CAP59 gene is involved in the synthesis of the capsule in Cryptococcus neoformans and Cryptococcus gattii, and is useful in the molecular identification of serotypes. In this research, we use yeasts of different serotypes from collection strains and C. neoformans isolates recovered from patients with cryptococcosis. A standardized yeast suspension from different Cryptococcus isolates as template allowed CAP59 gene amplification. This procedure was quick, simple, and inexpensive and required no PCR steps. This is important for taxonomic studies in laboratories with implemented molecular biology tools. PMID- 20589328 TI - [Methylene blue test for the determination of viability of free larvae of Trichinella spiralis]. AB - The present research was carried out with the purpose of determining whether or not the methylene blue test could also evidence viability of free larvae of Trichinella spiralis, taking into account its usefulness in the determination of viability of protoscolices in Echinococcus granulosus. To this end, three T. spiralis larval suspensions (M1, M2 and M3) were used, each containing 500 free larval stages. A hundred microl of methylene blue solution 1:10000 in distilled water were added to 100 microl of the larval suspension. Larvae were observed under optical microscopy to evaluate motility. M1 was exposed to -30 degrees C and could be observed on day 70, M2 was exposed to 80 degrees C during 5 minutes and it was immediately observed under optical microscopy, and M3 was maintained at 4 degrees C during the experiment as a 100% viability testing. Our results indicated that when T. spiralis larvae took up 100% of the methylene blue stain (M1 and M2), their inner structures appeared not only retracted but also stained blue, whereas in the M3 suspension test, larvae remained unstained and 100% of them showed their typical spiral-like movement. PMID- 20589329 TI - [Seroprevalence of the swine influenza virus in fattening pigs in Argentina in the 2002 season: evaluation by hemagglutination-inhibition and ELISA tests]. AB - The seroprevalence of the Influenza virus against H1N1 and H3N2 was determined by the hemagglutination-inhibition test (HI) and a commercial swine influenza ELISA kit, in 13 Argentinean swine herds. The results of within-herd and between-herd prevalence obtained by both tests were statistically correlated. The within-herd prevalence observed by the HI test varied from 38.46 to 100% against H1 and 7.69 to 100% for H3. When the within-herd prevalence was measured with the ELISA test, it varied from 2.33 to 6.9% for H1 and 9.65 to 48% for H3. No statistical differences were observed at herd level between HI and ELISA (H1: p = 0. 20; H3: p=0.11). No agreement between HI and ELISA detected prevalence was observed when the within-herd prevalence was compared (H1: 0.005; H3: 0.070), while the agreement at herd level was considered poor (H1: 0,350; H3: 0,235). The high within-herd prevalence values observed with the HI test and the high sensibility of this test might show that human strains or swine strains phylogenetically closely related to the humans strains used in the HI test in this study have been affecting the swine population since 2002. PMID- 20589330 TI - [Anaerobiosis beyond anaerobic bacteria: its role in the recovery of aerobic microorganisms from purulent samples]. AB - The main objective of incubation in anaerobiosis is the recovery of obligate anaerobic bacteria, not excluding other microorganisms. In 2003, we conducted a comparative and prospective study from consecutive clinical samples on the recovery of aerobic microorganisms from primary cultures both in anaerobiosis and aerobiosis of the same sample. The aims were to evaluate the methodology used in anaerobiosis in the recovery of aerobic microorganisms not diagnosed in primary aerobic cultures, and to establish a relationship between them and the origin of the sample. From 2003 to 2004, 2776 bacteriological samples were analyzed and 1884 aerobic microorganisms were cultured altogether. The result was that 69.4% of the samples showed growth both in aerobic and anaerobic incubation from primary cultures of the sample, whereas 30.6% only in one of the mentioned incubation atmosphere: 49.2% in aerobiosis and 50.8% in anaerobiosis. According to these results, the methodology used in anaerobiosis (anaerobic incubation, culture media, stereoscopic microscope or hand lens to examine the primary plates), allowed an extra yield of aerobic organisms, especially gram positive facultative and microaerophilic cocci, which was particularly evident in polimicrobial cultures, and especially when gram negative accompanying flora was present, independently of the type of sample. PMID- 20589331 TI - [Optimization of processing and storage of clinical samples to be used for the molecular diagnosis of pertussis]. AB - Pertussis or whooping cough is an acute, highly contagious respiratory infection, which is particularly severe in infants under one year old. In classic disease, clinical diagnosis may present no difficulties. In other cases, it requires laboratory confirmation. Generally used methods are: culture, serology and PCR. For the latter, the sample of choice is a nasopharyngeal aspirate, and the simplest method for processing these samples uses proteinase K. Although results are generally satisfactory, difficulties often arise regarding the mucosal nature of the specimens. Moreover, uncertainties exist regarding the optimal conditions for sample storage. This study evaluated various technologies for processing and storing samples. Results enabled us to select a method for optimizing sample processing, with performance comparable to commercial methods and far lower costs. The experiments designed to assess the conservation of samples enabled us to obtain valuable information to guide the referral of samples from patient care centres to laboratories where such samples are processed by molecular methods. PMID- 20589332 TI - Bacterial pathogens associated with bloody diarrhea in Uruguayan children. AB - Diarrheal disease continues to be a serious health problem, especially in developing countries. Bloody diarrhea represents approximately 20-30% of all cases and has higher morbidity and mortality. Treatment with antibiotics is beneficial in cases of Shigella, Campylobacter, Yersinia and Salmonella infection, principally in those children with a higher risk of invasive disease. The aims of this study were to detect the bacterial agents associated with bloody diarrhea in children and to determine their antimicrobial susceptibility patterns. Between June 2001 and January 2008, 249 children with bloody diarrhea were studied. Shigella and Shiga toxin-producing Escherichia coli (STEC) were recovered from 48 (19.3%) and 3 (1.2%) of the total of cases, respectively. In 49 out of 249 children, in whom other enteropathogens were investigated, we recovered Campylobacter jejuni from 7 children (14.3%), Salmonella spp. from 2 (4.1%) and Aeromonas spp. from 1 (2%) in addition to Shigella from 7 children (14.3%). Thirty-four (70%) Shigella isolates showed resistance to ampicillin and 13 (27%) to trimethoprim-sulfamethoxazole. All Shigella isolates were susceptible to nalidixic acid, ciprofloxacin and ceftriaxone. Salmonella and STEC isolates were susceptible to all antibiotics assayed. Thus, the use of trimethoprim sulfamethoxazole or ampicillin would not be appropriate for the empirical treatment of Shigella - associated diarrhea. PMID- 20589334 TI - [Acanthamoeba sp. keratitis: first case confirmed by isolation and molecular typification in Bahia Blanca, Buenos Aires Province, Argentina]. AB - Some species of the Acanthamoeba genus cause keratitis, a very painful, most likely unilateral corneal infection , associated with eye and vision impairment. We here present a case of a 31-year-old female patient, a regular user of soft contact lenses without good practices of lens hygiene and handling. The patient attended medical consultation after two months of inflammation and pain in her right eye. After ophthalmological studies, and due to suspicion of a parasitic infection, a biopsy was performed and the sample submitted for bacteriological and parasitological analyses. Moreover, contact lens holders and lens cleaning solutions were studied. The samples yielded negative results for bacterial infection. However, cultivation of all samples showed the presence of amoeboid parasites. Isolated amoebae were morphologically and molecularly classified as members of the Acanthamoeba genus. This is the first case of keratitis caused by Acanthamoeba in Bahia Blanca, Buenos Aires Province, where the parasite was identified by specific and sensitive molecular techniques. PMID- 20589333 TI - [Recidivant laryngeal leishmaniasis: an unusual case in an immunocompetent patient treated with corticosteroids]. AB - Leishmaniosis is a chronic parasitic disease, which in Argentina is mainly caused by protozoa belonging to the Leishmania (Viannia) braziliensis complex, leading to cutaneous and mucosal pathologies. We report a rare case of laryngeal leishmaniosis in a 29 year-old man from Jujuy province, Argentina, who had been misdiagnosed with other pathologies, carrying this infectious disease for about 20 years. During 2008, the patient was admitted with complaints of progressive hoarseness of the voice and dyspnea. He also reported having received tuberculostatics, antifungal and corticosteroids treatments since 2002. Different biopsies and direct laryngoscopic exams revealed inespecific granulomatous larynx, TBC-related laryngitis, laryngitis related to Histoplasma infection, extra-nodal Natural Killer-cell lymphoma. Finally, the patient was evaluated at the University Hospital and the final diagnosis was: granulomatous larynx, intra and extra-cytoplasmic Leishmania spp amastigotes, negative for TBC and Histoplasma cultures, and chronic laryngitis related to Leishmania infection, according to the laryngeal endoscopy, microbiological and histopathological exams, respectively. The patient received pentavalent antimonial treatment and his condition improved after 2 months of follow-up. Primary laryngeal leishmaniosis is rare and this localization does not belong to the most prevalent mucosal leishmaniosis. However, this parasitic disease warrants special concern, especially in patients who received prolonged corticosteroid treatments, in order to avoid a misdiagnosis of this disease. PMID- 20589336 TI - [Quality of commercial inoculants for soybean crop in Argentina: concentration of viable rhizobia and presence of contaminants]. AB - In view of the inoculant production technology available, quality control is a necessary tool to improve soybean inoculants commercialized in Argentina. In 1988, the Facultad de Ciencias Agropecuarias de la Universidad Nacional de Entre Rios (Argentina) created a quality control service for soybean crop inoculants to offer to farmers. The aim of this study was to evaluate the quality of soybean crop inoculants for seven cropping seasons and to contrast these results with those from previous investigations conducted in our country. This work was developed using 128 inoculant samples from 30 different trade names. The analyzed variables were: inoculant label information, number of viable rhizobia and presence of contaminants. Twenty per cent of the labels showed defects that did not comply with the Argentine legislation. The detected problems in inoculant labels were related to lot numbers or the expiry date, which lacked, was easy to remove or not visible. Eighty seven per cent of the analyzed inoculants were formulated in liquid carriers. Seventy six per cent of the samples had a number of rhizobia above 10(8) CFU/g or ml, the minimum quantity required by the legislation. Thirty per cent of the analyzed inoculants had contaminants and their presence was related to low rhizobia counts, as shown in a correspondence analysis. The relationship between liquid inoculants and the absence of contaminants was expressed. It can be concluded from the comparison of results found in this investigation with those in previous works published on Argentinean inoculants, that inoculant quality has been improved, although the situation is far from ideal. Adequate manufacturing and commercialization controls are necessary to ensure product quality. PMID- 20589335 TI - Isolation of Leptospira interrogans from suburban rats in Tandil, Buenos Aires, Argentina. AB - The main objective of this study was to investigate the role of wild rodents as Leptospira spp. reservoirs in a suburban area of Tandil city, Buenos Aires province (Argentina), where a person had died due to pulmonary leptospirosis. The specific objectives were: to estimate the rodent density near the patient's home, to determine the serological prevalence and isolation of leptospirosis from wild rodents, and to identify the isolated strains. The area examined was a suburban neighbourhood in Tandil near the Langueyu stream, where the patient's house is located. Rattus norvegicus were trapped on the stream banks during two nights and a high capture rate (70%), was obtained. All rats (42) were examined serologically by the microscopic agglutination test (MAT), and 22 of them (52.3%) reacted with Leptospira serovars castellonis, canicola, grippotyphosa, icterohaemorrhagiae and hebdomadis at a titer of 1:50. The kidneys from 25 animals were cultured, and 24 isolates of L. interrogans (96%) were obtained. The isolated strains were identified as Icterohaemorrhagiae serogroup by MAT performed with rabbit hyperimmune reference sera. These findings showed a high density of suburban rodents highly infected with pathogenic leptospira, sharing environment in close contact with humans with evidence of leptospiral disease. PMID- 20589337 TI - Arbuscular mycorrhizal infection in two morphological root types of Araucaria araucana (Molina) K. Koch. AB - Araucaria araucana (Molina) K. Koch is a conifer distributed in the Andean Patagonian forests in the south of Argentina and Chile. The main objective of this work was to relate the different root classes appearing in A. araucana to mycorrhizal behavior. Samples were collected in three different sites in the Lanin National Park (NW Patagonia, Argentina). Two different root classes were present in A. araucana: longitudinal fine roots (LFR) and globular short roots (GSR). Both had extensive mycorrhizal arbuscular symbiosis (AM) and presented abundant hyphae and coils in root cells, a characteristic of the anatomical Paris type. Dark septate fungal endophytes were also observed. Values of total AM colonization were high, with similar partial AM% values for each root class. Seasonal differences were found for total and partial colonization, with higher values in spring compared to autumn. Regarding the percentage of fungal structures between root classes, values were similar for vesicles and arbuscules, but higher coil percentages were observed in GSR compared to LFR. The percentages of vesicles increased in autumn, whereas the arbuscule percentages increased in spring, coinciding with the plant growth peak. Results show that both root classes of A. araucana in Andean-Patagonian forests are associated with AM fungi, which may have ecological relevance in terms of the importance of this symbiosis, in response to soil nutrient-deficiencies, especially high P-retention. PMID- 20589338 TI - Tn7::In2-8 dispersion in multidrug resistant isolates of Acinetobacter baumannii from Chile. AB - Acinetobacter baumannii is considered an important pathogen in our hospital environment having a well-known capacity to acquire different mechanisms of antibiotic resistance. Previous studies in our laboratory had exposed the high dispersion of class 2 integrons in this species. In the present study, we analyzed 7 multiresistant intI2 positive A. baumannii isolates, 6 of which were found to harbour the Tn7::In2-8 element. Our results demonstrate the unusually high distribution of Tn7::In2-8 among different A. baumannii clones from Chile, suggesting a particular behavior of these elements at geographical level. PMID- 20589339 TI - [Participation of microbial communities in the bio-deterioration of rocks of historical /cultural importance.]. PMID- 20589340 TI - [Trypanosoma cruzi in the cerebrospinal fluid of an AIDS patient]. PMID- 20589341 TI - [rHuGM-CSF: a possible therapeutic treatment in resistant chronic wound healing: our first observations]. AB - Skin wounds are exposed to a complex series of events that usually culminate in wound healing. This process is well known in relation to histological events, although mechanisms that underlie its regulation remain unclear at a molecular level; not only tissue growth factors but also a number of cytokines are involved. In this paper we report our experience in two cases about the treatment of resistant chronic ulcers of lower limbs using GM-CSF human recombinant: rHuGM CSF as a topic treatment over 8 weeks. The results consist in a complete healing in one patient and in excellent improvement in the other one. Accordingly, we realized the idea that GM-CSF could be included between compounds able in promoting healing, in relation to direct or indirect effects in relation of its topical GM-CSF use. However, further study will be needed to determine dosage, method of application and type of recombinant material to be used for best results. PMID- 20589342 TI - [Impact of depression syndrome in the management of cardiovascular risk factors in primary prevention: State of the art]. AB - Our aim is to investigate, through a broad review of medical literature, the role of depressive syndrome on the adherence to lifestyle modifications (TLC) in patients with risk factors for cardiovascular disease (CVD). We conducted a systematic computerized literature search of MEDLINE using the following key words: depressive syndrome, cardiovascular risk factors, lifestyle, physical activity, diet, smoking, blood pressure, metabolic syndrome and diabetes. We have considered metanalyses studies, reviews, original articles, case-control studies published between 1992 and 2010. Furthermore, we have considered the impact of depressive syndrome on the different cardiovascular risk factors. From our search we have selected 42 English articles published between 1992 and 2010 of whose 16 were longitudinal cohort studies, 5 research reports, 10 longitudinal case control studies, 2 metanalyses, 5 reviews and 4 prevalence studies. All our selected studies agree to give to depressive syndrome a negative role on the adherence to lifestyle modifications. For this reason, depression represents an indirect and independent cardiovascular risk factor that needs to be detected and treated for a successful cardiovascular prevention. PMID- 20589343 TI - [Delirium and psychotropic substance abuse]. AB - Delirium represents a common symptom in psychiatric diseases such as psychotic and affective disorders, organic illnesses and psychotropic substance abuse. The literature shows a high risk of developing psychosis in psychotropic substance abusers and a higher proneness to psychotropic substance abuse in people suffering from psychosis. The aim of this review is to discuss the relationship between substance abuse (cocaine, amphetamine, alcohol, cannabinoids, opioids, etc.) and the development of delirium, the way each molecule influences the pathogenesis of delirium, the neurochemical basis of delirium induced by psychotropic substances and the potential endophenotypes involved in a biologically plausible mechanism of mental diseases' pathogenesis. PMID- 20589344 TI - [The psychopathology of delirium. Evolution of the research from Jaspers to Kapur]. AB - Delirium represents a symptom of a thought disorder in which a belief is strongly held in spite of invalidating evidence. Many varieties of delirium have been described and this symptom is common in psychotic disorders (schizophrenia, brief psychotic disorder, chronic delusional disorders, etc.), affective disorders (major depressive disorder, psychotic depression, melancholic depression, bipolar disorder, etc.), organic illnesses and psychotropic substance abuse. Delirium has been deeply studied by psychopathology. Our work offers an overview of the most relevant psychopathological descriptions of delirium in the last century, from Jaspers to Kapur. PMID- 20589345 TI - Physiopathological, clinical and therapeutic aspects of hepatopulmonary syndrome. AB - Patients with cirrhosis or portal hypertension may develop hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHT). HPS occurs in 25% of the subjects with chronic hepatopathy waiting for a liver transplantation. HPS is characterized by chronic hepatopathy and/or portal hypertension, increased P(A a)O2 gradient (more than 20 mmHg) with hypoxemia and intrapulmonary vascular dilatations without a primary cardiovascular disease. Hypoxiemia is due to intrapulmonary arteriovenous shunts and to dilatation of microvessels in basal parts of the lung and of pleural vessels. In patients with cirrhosis an impaired cardiovascular function is frequent, often in a subclinical phase of the disease. Left ventricular systolic and diastolic dysfunction may develop a chronic hepatopathy and the relation between right ventricular and liver failure has been studied. During cirrhosis characteristic alterations of systemic hemodynamic can cause the hyperdynamic circulatory syndrome. Contrast enhanced 2D ECHO cardiography is the preferred screening test for intrapulmonary arteriovenous shunts. The aim of HPS therapy is to contrast intrapulmonary vasodilatation, increased portal flux and hyperdynamic syndrome. New therapeutical agents are fosfodiesterase inhibitors, ET-1 receptor antagonists and selective NOS inhibitors. However, medical treatment is not much effective in HPS and liver transplantation is considered the only therapeutical chance. PMID- 20589346 TI - [Role of imaging in the evaluation and characterization of adrenal masses]. AB - The primary role of imaging in identification as well as in characterization adrenal lesions has been demonstrated by several studies. The recent technologic progress has allowed to identify adrenal lesions even when they are very small, with a consequent conspicuous increase of the frequency of incidentalomas. Computed Tomography, Magnetic Resonance and Nuclear Medicine are routinely used to evaluate adrenal glands and their pathologic conditions. The aim of this article is to show how the imaging is employed to assess adrenal masses, with special regard to the contribution given by Computed Tomography (CT) and Magnetic Resonance (MR) imaging to the differential diagnosis between benignant and malignant lesions. PMID- 20589347 TI - Oral administration of an association of forskolin, rutin and vitamins B1 and B2 potentiates the hypotonising effects of pharmacological treatments in POAG patients. AB - BACKGROUND/AIMS: Control of intraocular pressure is still the main strategy to treat glaucoma patients. Forskolin has already shown an ability to control intraocular pressure after topic administration, whereas rutin is known to improve ocular blood fl ow. Therefore, aim of this pilot study has been to observe whether administration of an association of oral forskolin and rutin to POAG patients under different regimens of medical therapy may contribute to their effects, further decreasing IOP values. MATERIALS AND METHODS: Forskolin (a natural compound present in the crude extract of the plant Coleus Forskohlii) and rutin are the main ingredients of a food supplement commercially available in Italy. In an open label pilot study, 16 patients with POAG under treatment with different topical drugs and with stable IOP were given additional treatment with the food supplement for 40 days, and their IOP values measured at enrolment, at the end of treatment and 40 days after treatment interruption. RESULTS: Further addition of forskolin and rutin to topical association treatments resulted in a further decrease of IOP by roughly 20% of the initial value. The effect was reversible upon suspension of the treatment. CONCLUSIONS: These data show for the fi rst time that forskolin and rutin given through the oral route appear to reach the ocular district, where they can act in synergy with topical pharmacological treatments, and contribute to the control of intraocular pressure. PMID- 20589348 TI - Intravitreal bevacizumab for treatment of myopic choroidal neovascularization: the second year of a prospective study. AB - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab for the treatment of myopic choroidal neovascularization (CNV). DESIGN: Prospective, non randomized, interventional clinical study. METHODS: Twenty eyes from 20 patients with CNV secondary to pathologic myopia participated in this study. These patients had already completed 12 months of follow-up. All patients were scheduled for 3 monthly intravitreal bevacizumab 1.25 mg injections. ETDRS best corrected visual acuity (BCVA), foveal center thickness (FCT) on OCT and CNV size as assessed by fluorescein angiography were examined before and after treatment. Patients were followed up for 24 months. RESULTS: Mean BCVA (+/- SD) at baseline was 24.8 (+/- 11.86) letters (Snellen equivalent: 20/80). At 24 months after treatment the mean BCVA (+/- SD) improved significantly (p less than 0.05) to 44 (+/- 13.99) letters (Snellen equivalent: 20/33). At 24 month follow-up, BCVA improved of 10 letters or more in 17 (85%) out of 20 treated eyes and improved of 15 letters or more in 15 (75%) eyes. No treated eyes experienced a worsening of BCVA from baseline. Mean foveal center thickness (FCT) (+/- SD) at baseline was 223 (+/- 47,43) microns. By month 24, mean FCT (+/-SD) reduced to 190 (+/- 29.01) microns (p less than 0.05). Mean area of the CNVs at baseline was 0.77 (+/- 0.78) mm2, which decreased to 0.31 +/- (0.51) mm2 and 0.30 (+/- 0.50) mm2 at 12 (p less than 0.05) and 24 months (p less than 0.05), respectively. At 24 months follow-up absence of fluoresce in leakage from the CNV was demonstrated in 18 (90%) out of 20 treated eyes. No ocular or systemic adverse effects from treatment were encountered. CONCLUSION: Eyes with myopic CNV treated with intravitreal bevacizumab over 2 years had significant anatomic and functional improvement. Further studies will be needed to confirm the long-term efficacy and safety of this treatment. PMID- 20589349 TI - Traumatic complex wounds, multidisciplinary approach: our experience in a case series. AB - "Limb-salvage" is a social problem that is rapidly increasing, both in Italy and in the rest of world. Today, as in earlier times, the main causes of open wounds are traumas and such injuries are mainly of II and III stage of Gustilo's classification. Nowadays, the use of modern techniques determined a further dramatic reduction in the infection rates and, above all, in the risk of limb amputation. The most important techniques include: V.A.C. therapy (vacuum assisted closure); PRP gel (platelet-rich plasma gel); hyperbaric oxygen therapy. We treated 4 patients with high energy acute trauma through the combined and innovative use of advanced dressings. The authors report their experience and a brief review of the literature as contribution in regards to treatment of complex wounds of the limbs. PMID- 20589350 TI - A 4-years-old girl with a mesenteric cyst. AB - This Letter to the Editor deals with the case of a 4-years-old female affected by a mesenteric cyst, initially confused with an ovarian cyst. The emergency situation justified our open approach. However, as expressed by the Authors, a laparoscopy should be always considered, also in pediatric age. PMID- 20589351 TI - [Informed consent. Doctor and patient: comparison of view points]. AB - Starting with an examination of the ethical and legal need for informed consent, the authors set out to assess the perception of the issue by physicians and patients, with particular reference to the Italian context, but also in comparison with international experience, which emerges from an analysis of the heterogeneous material on the Internet. Regardless of local laws, there seems to be a substantial overlap between the way in which the Italian community of doctors and patients and the international community experience informed consent, which often is not the assurance of an effective therapeutic relationship that we would like it to be. PMID- 20589352 TI - Morphometry of A1 segment of the anterior cerebral artery and its clinical importance. AB - BACKGROUND AND AIM: Anterior cerebral artery, one of the terminal branches of the internal carotid artery is an important vessel taking part in the formation of circle of Willis. It supplies a large part of the medial surface of the cerebral hemisphere containing the areas of motor and somatosensory cortices of the lower limb. Aim of this study was the morphometry of A1 segment of the anterior cerebral artery. MATERIALS AND METHODS: 93 formalin fixed brain specimen of either sex and of Indian origin were studied. The mean length, mean external diameter and the anomalies present in A1 segment of the vessel were studied in detail and photographed. RESULTS: The mean length of A1 segment of the vessel was 14.49+/-0.28 mm and 14.22+/-0.22 mm on right and left side respectively. The mean external diameter of the vessel on right and left side was 2.12+/-0.07 mm and 2.32+/-0.06 mm respectively. Narrowing, aneurysm formation, buttonhole formation and median anterior cerebral artery were the anomalies seen with an occurrence of 15.05%, 5.37%, 3.22% and 12.9%, respectively. The above anomalies did not have any sex or side predilection. CONCLUSION: Knowledge of morphometry of the vessel will be of use to neurosurgeons while performing the shunt operation, in assessing the feasibility of such operations and in the choice of patients. From this study we infer that the morphometry of anterior cerebral artery varies in different population and that the neurosurgeons operating should have a thorough knowledge of the possible variations. PMID- 20589353 TI - Antispermatogenic and antifertility effect of Pegaga (Centella asiatica L) on the testis of male Sprague-Dawley rats. AB - AIM: Antifertility agents with safety and effectiveness in terms of minimum side effects have always been a subject of debate. Many studies have been conducted on plants to observe the antifertility effect, but majority of them were toxic. Pegaga or Centella asiatica L. is one of the popular herb traditionally consumed raw amongst people in Malaysia. The main objective of the present study was to investigate the effects of Centella asiatica L. extract on rat testis. MATERIALS AND METHODS: Thirty two Sprague-Dawley adult male rats, (12 weeks) were divided into four groups:- (I) control group (with distilled water), (II) low dose group (with 100 mg/kg body weight extract), (III) medium dose group (with 200 mg/kg body weight extract), and (IV) high dose group (with 300 mg/kg body weight extract) and force fed for 42 days. The rats were then sacrificed and the testis were removed for histological analysis. RESULTS: The testis in the control group showed normal features with successive stages of transformation of the seminiferous epithelium into spermatozoa, whereas treated groups showed some degeneration of spermatogenic cells and reduction of spermatozoa in the lumen of the seminiferous tubules. Serum testosterone level was reduced in all treatment groups as compared to the control while cauda epididymal sperm count and motility showed significant decrease. Treatment with medium and high doses showed the most significant reduction (p<0.05) in sperm count. CONCLUSIONS: It is concluded that Centella asiatica L. exhibited antispermatogenic and antifertility effects on reproductive system of the male rats. PMID- 20589354 TI - Blepharoptosis in children: our experience at the light of literature. AB - AIMS: We herein report a 5 years experience of management and care of children presenting blepharoptosis at the light of the literature regarding this uncommon pathology. This report aims to display the most common causes of blepharoptosis and its possible treatment. PATIENTS AND METHODS: Clinical and epidemiological data collected from our institution, over a fi ve year period, on 60 patients, 37 males and 23 females with a mean age of 5.4 years (range 0.6 to 15.6 years) affected by blepharoptosis were analyzed. RESULTS: Ptosis was unilateral in 39/60 patients (65%) and bilateral in 21/60 (35%). The causes of ptosis were myogenic (40%), and neurogenic (35%), most commonly congenital. Among the neurogenic ptosis, the most frequent causes were PTOS type 1 and Marcus-Gunn syndrome. All the cases of acquired neurogenic ptosis were associated with paralysis of the oculomotor nerve. Ptosis plus was found in 23.3% of the patients, mechanical origin was present in 1.7% of patients. Family history was positive in the 10% of the patients. CONCLUSIONS: Our series reflect the range of ptosis of the general pediatric population. This study highlights the high degree of heterogeneity in patients with ptosis; only with an accurate analysis of the family and patient history and of the clinical features it is possible to perform an accurate diagnosis, finding the genetic causes and an adequate treatment. PMID- 20589355 TI - [Lymphocytes Fox P3 and chronic C hepatitis: preliminary results]. AB - OBJECTIVES: Characterization of Treg lymphocytes (CD4+CD25+) in immune response in patients with chronic viral hepatitis C. MATERIALS AND METHODS: Two groups of patients were included: Group A (10 patients with chronic hepatitis C); Group B (10 healthy controls). In both groups, liver markers, liver function tests, lymphocyte typing, serum HCV-RNA were assessed. Liver biopsy was executed in Group A only. Peripheral venous samples were analyzed by citofluorimetric analysis, liver biopsy's samples were studied by immunohistochemistry. RESULTS: Group A patients showed a larger expression of Treg (CD4+CD25+) in peripheral blood than Group B with an ipo-expression of a subpopulation of Treg FoxP3+ (CD4+CD25hi). Group B patients showed a higher ratio (CD4+CD25hi/CD4+CD25+) than Group A. Liver biopsy samples showed a clear positivity for FoxP3+ Treg cells in the inflammatory infiltrated. CONCLUSION: Our study's preliminary results seem to indicate that Treg lymphocytes are really involved in flogistic process in course of chronic hepatitis C. Peripheral blood of infected patients (Group A) shows a low expression of Foxp3+ cells because they are sequestrated in the liver. These cells could be involved in the pathogenesis of the chronic disease and they would be employed how potential agents for a immunomodulatory therapy. PMID- 20589356 TI - Anatomy of plantaris muscle: a study in adult Indians. AB - AIM: The plantaris muscle (PM) and its tendon is subject to considerable variation in both the points of origin and of insertion. The present study was carried out to fi nd the different types of origin, insertion and possible variations of the PM in the population of southern costal region of India. MATERIALS AND METHODS: 52 embalmed (Formalin fixed) cadaver lower limbs of 26 males (age ranged 48-79 years, mean age 68 years) were dissected, to study the origin and insertion of PM. Various dimensions (length and width) of plantaris muscle belly and its tendon were also measured. RESULTS: Three types of origin and equal number of insertion were noticed in the present study. The PM took origin from type I: Lateral Supracondylar ridge, Capsule of Knee joint and Lateral head of gastrocnemius in 73.07% cases; type II: Capsule of Knee joint and Lateral head of gastronemius in 5.76% cases; type III: Lateral Supracondylar ridge , Capsule of Knee joint , Lateral head of gastrocnemius and fibular collateral ligament in 13.46% cases. The plantaris tendon was inserted into type I: to the flexor retinaculum of foot in 28.84% cases; type II: independently to the os calcaneum in 36.53% cases; type III: to the tendocalcaneus at various levels in 26.92% cases. In four lower limbs (7.69%) the plantaris muscle was completely absent. Additionally the length and width of the plantaris muscle and its tendon were measured to know any side difference. There were no statistically significant differences between the measurements of left and right side (p>0.05). CONCLUSION: Present study will help the surgeons while attempting various surgical procedures in and around the posterior aspect of knee involving plantaris. PMID- 20589357 TI - Combination of morphology, flow cytometry and PCR assay to detect bone marrow infiltration in B-cell non-Hodgkin's lymphomas. AB - AIMS: Morphology on bone marrow biopsy (BMB) samples has historically been the primary method used to detect bone marrow (BM) infiltration in B-cell non Hodgkin's lymphoma (NHL), while fl ow cytometry (FC) and PCR assays have been generally used as ancillary methods. In this study we evaluated a combined approach utilizing all three methods to detect BM infiltration in patients with NHL both at diagnosis and after therapy. MATERIALS AND METHODS: We analyzed 193 patients with NHL, who received simultaneous BMB, FC and PCR assays. Morphology on histologic specimens was used to assess infiltration pattern and immunohistochemistry, FC to analyze immunophenotype, PCR to identify IgH rearrangement, BCL-1/JH and BCL-2/JH translocation. RESULTS: Morphology, FC and PCR assays agreed in 142 cases (73.5%) with more concordance at initial diagnosis than during postchemotherapy follow-up. PCR was the single best-performing test, while combination of morphology and PCR yielded a higher sensitivity than individual methods and was similar to PCR + FC. We observed little added benefit using a third approach. CONCLUSION: Given the initial importance of histological information evident by morphology, our data suggest that combination of morphology and PCR should be considered the gold standard for evaluation of BM infiltration at diagnosis, while combination of PCR + FC should be employed during post-treatment follow-up. PMID- 20589358 TI - Clinico-anatomical aspects of accessory fissures obscuring the normal hepatic morphology. AB - Interesting observations were discovered in a liver specimen during routine educational dissection class. Accessory fissures were observed on the visceral surface of the liver. One fissure was observed to delineate an accessory lobe from the quadrate lobe distorting the configuration of the quadrate lobe. The other fissure was seen demarcating the caudate lobe from its process. These fissural variations are detectable by ultrasonography and adequate knowledge of the normal morphology of the liver may prevent erroneous diagnosis of a focal intrahepatic lesion. We undertook the task of reporting this rare anomaly of this vital organ so that the operating surgeons and radiologists are cautioned adequately before striving to approach the liver. PMID- 20589359 TI - An unexpected case of primary peritoneal carcinoma. AB - Primary peritoneal carcinoma (PPC) is a rare tumor that is histologically and immunohistochemically indistinguishable from epithelial ovarian carcinoma. The diagnosis is usually made after excluding gross ovarian involvement or the ovarian involvement is only confined to the surface. A 68-year-old lady presented with right iliac fossa pain and increasing CA125. The CT scan showed bilateral pelvic adnexal masses with peritoneal deposits within the right side of abdomen. She was initially diagnosed as carcinomatosis peritonei from the omental cake removed after exploratory surgery. She was managed as advanced ovarian tumor with peritoneal metastasis and was then administered six cycles of chemotherapy. Surgical intervention included debulking surgery consisting of total abdominal hysterectomy, bilateral salpingooophorectomy and omentectomy and also with right hemicolectomy. The histopathological findings were of primary peritoneal serous carcinoma with only minimal involvement of the serosal surface of the right ovarian capsule. No microscopic invasion into underlying ovarian cortex and stroma was observed. Multiple tumor deposits were also seen over the right paratubal and paraovarian tissue, both parametrium as well as serosal surface of the terminal ileum and periappendicular tissue. Immunohistochemically, the malignant cells were positive to CA125, focally positive to CK7 and negative to CD20 and Calretinin. PPC is one of important differential diagnosis which needs to be considered in cases of advanced ovarian tumor, although the former can only be ascertained after excluding the ovarian involvement microscopically. PMID- 20589360 TI - Fusariosis and skin T cell lymphoma: concomitant more than a differential diagnosis. AB - Cytotoxic T cell lymphomas of the skin include a spectrum of a peripheral T cell and natural killer (NK) cell lymphomas with primary and secondary skin manifestation and bad prognosis. Fusarium species have recently emerged as the second most common pathogenic fungi in immunocompromised patients, and they are moderately resistant to most antifungal agents. We report a woman with concomitant cytotoxin T cell lymphomas of the skin and Fusarium spp infection. Patient was treated at the same time with antiblastic and antifungal therapy. First line antifungal therapy was amphotericin B-lipid complex (3 mg/Kg iv/die) and then for clinical failure voriconazole (6 mg/Kg bid, loading dose and 4 mg /Kg bid). Lymphoma was treated with a CHOEP 21 regiment without remission and after with gemcitabine and vinerolbine. Patient presented a partial remission of cutaneous and pulmonary lesions. Our case is intrinsically interesting because Fusarium infection was concomitant to cutaneous lymphoma and did non occur during neutropenic phases of chemotherapy. In a case with multiple ulcerated nodules of the skin is very important to discriminate from disseminated cutaneous Fusarium infection and neoplastic conditions such as cutaneous lymphoma. Early treatment of Fusarium infection in a patient with neoplastic disease could avoid a dissemination during immunosuppressive condition caused by antiblastic therapy. PMID- 20589361 TI - [Obstructive Sleep Apnea Syndrome (OSAS): The role model of the Occupational Health Physician in specific clinical cases.]. AB - Nowadays Sleeping disorders are a very interesting topic in Occupational medicine, they are involved in reduction of working performances and increased risk of work accidents (in work environment or while driving). Medical surveillance made from the Occupational Health Physician can be very helpful in early diagnosis of this kind of disease; during 2008 we fi nd out Obstructive Sleeping Apnea Disease (OSAS) in some Healthcare workers. We reported some clinical cases that show the role model of the occupational health physician in this kind of sickness. Our Experience shows the duty of Occupational health physician it's not limited to medical surveillance, but also to Health Promotion (as wrote in D.Lgs 81/08). This can be obtained by clinical and occupational solutions, like correct work shift planning and lifestyle changes; so the interest of the occupational physician have to be focused on introducing in medical surveillance also measures of health promotion regarding sleep disorders with the aim of preserving health condition in workers. PMID- 20589362 TI - Diagnosis. AB - The paper deals with the term Medical Diagnosis (D). It is the process of identifying a disease by its signs, symptoms and results of various diagnostic (laboratory or imaging) procedures. D. is part of clinical reasoning. It includes the following phases: 1. observation (anamnesis, medical examination); 2. problem determination; 3. hypotheses generation; 4. hypothesis control (through laboratory and imaging tests); 5. working D.; 6. therapeutic/caring decisions; 7. final D., 8. follow-up. In order to choose correctly a diagnostic test (DT), it is necessary to answer the following questions: 1. Is an evidence about the accuracy of a DT valid? 2. Does the valid evidence show that this test can accurately distinguish patients who do and do not have a specific disorder? 3. How applying a valid, accurate diagnostic test to a specific patient? PMID- 20589363 TI - Epistemology. AB - This entry begins by presenting the origin, history and etymology of the term, as well as a short definition of epistemology as the discipline that deals with the nature, origin, validity and limits of knowledge. Then we focus on the classical platonic analysis of knowledge as truth justified belief. Against the backdrop of this platonic notion we present other relevant perspectives. It is essential to follow the history of the relation between origin and justification of knowledge until the contemporary separation of both problems. The study of the origin of knowledge seems to require a naturalized epistemology, while the problem of justification is usually approached from a philosophical point of view, whether coherentist, foundationalist or fallibilist. However, currently some authors are advocating for a full naturalized epistemology, while others are extending the philosophical point of view also to the genesis of knowledge. PMID- 20589364 TI - Ethics committees. AB - Ethics committees (ECs) are a relevant body for dealing with ethical issues in healthcare. They born in order to resolve dilemmatic situations. Contemporary ECs are independent standing committees with multidisciplinary representation, including medicine, nursing, social work, law, pastoral care, healthcare administration, and other different expertises. The functions of ECs are various: estimating clinical trials; analyzing ethically relevant clinical cases; drafting hospital/organizational guidelines, and to carry out education activity. The composition and kind of skills requested in an EC could change according to national laws. About international ethical standards in clinical experimentation, the World Medical Association's Declaration of Helsinki is the reference according to which examining clinical trials by ECs. PMID- 20589365 TI - Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling. AB - Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches. PMID- 20589366 TI - Identification of the blast resistance gene Pit in rice cultivars using functional markers. AB - DNA markers that allow for identification of resistance genes in rice germplasm have a great advantage in resistance breeding because they can assess the existence of the genes without laborious inoculation tests. Functional markers (FMs), which are designed from functional polymorphisms within the sequence of genes, are unaffected by nonfunctional allelic variation and make it possible to identify an individual gene. We previously showed that the resistance function of the rice blast resistance gene Pit in a resistant cultivar, K59, was mainly acquired by up-regulated promoter activity through the insertion of a long terminal repeat (LTR) retrotransposon upstream of Pit. Here, we developed PCR based DNA markers derived from the LTR-retrotransposon sequence and used these markers to screen worldwide accessions of rice germplasm. We identified 5 cultivars with the LTR-retrotransposon insertion out of 68 rice accessions. The sequence and expression pattern of Pit in the five cultivars were the same as those in K59 and all showed Pit-mediated blast resistance. The results suggest that the functional Pit identified using the markers was derived from a common progenitor. Additionally, comparison of the Pit coding sequences between K59 and susceptible cultivars revealed that one nucleotide polymorphism, which caused an amino acid substitution, offered another target for a FM. These results indicate that our DNA markers should enhance prediction of Pit function and be applicable to a range of rice varieties/landraces cultivated in various regions worldwide and belonging to the temperate japonica, tropical japonica, and indica groups. PMID- 20589367 TI - Investigation of the cyanuric acid contamination caused by acetonitrile and alkali detergent for the LC-ESI MS/MS analysis. AB - During the replicate analysis of melamine and cyanuric acid by LC-ESI MS/MS for the method development, recurring cyanuric acid contamination was observed. The high concentration (6,950 mg/kg) of cyanuric acid was found in the strong alkali detergent used in a glassware washing machine. However, only small concentration of cyanuric acid (0.002-0.004 mg/kg) was detected in the glassware washed with the above alkali detergent. The major contamination source of cyanuric acid was some specific lot of acetonitrile (0.093 mg/kg) that increased the background level of the ion chromatogram. PMID- 20589369 TI - Study of epsilon-caprolactone polymerization by NIR spectroscopy. AB - Near-infrared (NIR) spectroscopy is proposed for the in-line quantitative and kinetic study of the polymerization of epsilon-caprolactone and eventually to facilitate real-time control of the manufacturing process. Spectra were acquired with a fibre-optic probe operating in transflectance mode immersed in the reactor. The NIR data acquired were processed using a multivariate curve resolution alternating least squares (MCR-ALS) algorithm. The proposed method allows calculation of the concentration and spectral profiles of the species involved in the reaction. The key point of this method is the lack of reference concentrations needed to perform the MCR-ALS method. The use of an extended spectral matrix using both process and pure analyte spectra solves the rank deficiency. The concentration profiles obtained were used to calculate a kinetic fitting of the reaction, but the method was improved by applying kinetic constraints (hard modelling). The rate constants of batches at different temperatures and the energy of activation for this reaction were calculated. Whenever possible, the hard modelling combined with the MCR-ALS method improves the fit of the experimental data: the results show good correlation between the NIR and reference data and allow the collection of high-quality kinetic information on the reaction (rate constants and energy of activation). PMID- 20589368 TI - Efficacy, side effects and route of administration are more important than frequency of dosing of anti-osteoporosis treatments in determining patient adherence: a critical review of published articles from 1970 to 2009. AB - The purposes of the study were to review available published literature on magnitude of non-adherence with osteoporosis regimens and to determine the association between frequency and modality of medication administration with patient preference and adherence. We searched peer-reviewed journal databases- MEDLINE, EMBASE, Biosis and Derwent Drug File for publications (January 1979 to January 2009) including MeSH terms--"patient preference", "adherence" and "compliance" based on "dosing frequency" and "modality". Since adherence was difficult to accurately quantify, preference, compliance and persistence were evaluated. Patients' preference and adherence at 12 months were higher with weekly over daily bisphosphonates (>= 84% preference for weekly, medication possession ratios (MPR) 60-76% vs 46-64%; persistence 43.6-69.7% vs 31.7-55.7%). MPR reported for oral bisphosphonates were 68-71% at 12 months. At 2 years, only 43% of patients had MPR >= 80% for daily and weekly bisphosphonates. Observational studies (6-12 months) reported discontinuation rates of 18-22% for daily and 7% for weekly bisphosphonates. Data on monthly bisphosphonates are conflicting and confounded by cost differences, patient support programmes and definition of persistence. Studies suggest patient preference for annual zoledronic acid infusions over weekly bisphosphonates (66.4-78.8% vs 9.0-19.7%, respectively), but no data on compliance or persistence are available. Drug effectiveness, side effects and route of administration were more important than frequency. Although less frequent dosing is preferred, other factors such as perceived efficacy, side effects, medication cost, availability of patient support programmes and route of delivery are equally important. Adherence is complex and difficult to quantify and may not be exclusively influenced by frequency of medication administration. PMID- 20589370 TI - Reproductive consequences of exposure to waterborne phytoestrogens in male fighting fish Betta splendens. AB - Phytoestrogens are plant compounds that can act as endocrine disruptors in vertebrates. Biologically active levels of phytoestrogens have been found in aquatic habitats near wood pulp and paper mills, biofuel manufacturing plants, sewage-treatment plants, and agricultural fields. Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success. In one experiment, we exposed sexually mature male fighting fish Betta splendens to environmentally relevant (1 MUg L(-1)) and pharmacological concentrations (1000 MUg L(-1)) of the phytoestrogen genistein as well as to a positive control of waterborne 17beta estradiol (E2; 1 MUg L(-1)), and a negative control of untreated water. In a second experiment, we exposed male B. splendens to environmentally relevant concentrations (1 MUg L(-1)) of genistein and beta-sitosterol singly and in combination as well as to the positive and negative controls. All exposures were 21 days in duration. We measured sex-steroid hormone levels, gonadosomatic index (GSI), sperm concentration and motility, and fertilization success in these fish. We found that exposure to genistein did not affect circulating levels of the androgen 11-ketotestosterone or the estrogen E2 relative to negative-control fish. We also found that neither of the compounds nor their mixture affected GSI, sperm concentration or motility, or fertilization success in exposed fish relative to negative-control fish. However, fish exposed to phytoestrogens showed some evidence of fewer but more motile sperm than fish exposed to the positive control E2. We conclude that sexually mature male B. splendens are relatively immune to reproductive impairments from short-term exposure to waterborne phytoestrogens. PMID- 20589371 TI - A survey of dietary intake of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like coplanar polychlorinated biphenyls from food during 2000-2002 in Osaka City, Japan. AB - Studies of the dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like coplanar polychlorinated biphenyls (dioxin-like PCBs), collectively referred as dioxins, were conducted using the total diet study (TDS) method with food purchased in Osaka City, Japan during 2000-2002. The daily intake of dioxin-TEQ (toxic equivalent) from food per adult person was estimated respectively as 104.24 pg TEQ/person/day in 2000, 72.73 pg TEQ/person/day in 2001, and 87.28 pg TEQ/person/day in 2002, corresponding to 2.08, 1.45, and 1.74 pg TEQ/kg body weight (bw)/day for an adult weighing 50 kg. The highest contribution ratio to the total intake of dioxin-TEQ was from fish and shellfish (group 10) in each year, accounting for 77-92%. The next highest contributor was meat and eggs (groups 11-A and 11-B). An annual decrease of the intake of dioxin-TEQ was not observed clearly. Otherwise, the dietary intake of non-2,3,7,8-substituted PCDDs/PCDFs were estimated together. The intake of 1,3,6,8-TeCDD came mostly from intake of fish and shellfish (group 10), green vegetable (group 7), and the other vegetables, including mushrooms and seaweed (group 8). In addition, the intake of 1,3,6,8-TeCDF, which reportedly antagonizes 2,3,7,8-TeCDD-mediated aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction activities, was an insufficient amount to suppress 2,3,7,8-TeCDD-mediated activities. Furthermore, we discussed different TEQ compositions of PCDDs/PCDFs to dioxin-like PCBs from food intake and in human samples and inferred that the difference was caused by low bioaccumulation properties of 3,3',4,4',5-PeCB (PCB 126). PMID- 20589372 TI - Ristocetin-induced self-aggregation of von Willebrand factor. AB - Von Willebrand factor (VWF) is a large multimeric adhesive glycoprotein, with complex roles in thrombosis and hemostasis, present in circulating blood and in secretory granules of endothelial cells and platelets. High shear stress triggers conformational changes responsible for both binding to the platelet receptor glycoprotein GpIb and its self-association, thus supporting the formation of platelet plug under flow. Ristocetin also promotes the interaction of VWF with GpIb and is able to induce platelet aggregation, and thus is largely used to mimic this effect in vitro. In this research paper, we followed the time course of VWF self-association in solution induced by ristocetin binding by light scattering and at the same time we collected atomic force microscopy images to clarify the nature of the assembly that is formed. In fact, this process evolves initially through the formation of fibrils that subsequently interact to form supramolecular structures whose dimensions would be capable of trapping platelets even in the absence of any degree of shear stress or interaction with external surfaces. This intrinsic property, that is the ability to self-aggregate, may be involved in some pathological settings that have been revealed in clinical practice. PMID- 20589373 TI - Economic evaluation of nuclear medicine procedures. PMID- 20589375 TI - Cutting-balloon angioplasty in transplant renal artery stenosis as first-line treatment in the early postoperative period. AB - Percutaneous transluminal angioplasty has been successfully used for the treatment of transplant renal artery stenosis (RAS). Cutting-balloon angioplasty (CBA) is being used as a second option in pressure-resistant stenosis. It is thought that CBA is less traumatic and therefore restenosis occurs less frequently than in conventional angioplasty. This case report describes the unusual use of a cutting balloon in transplant RAS as a first option in the early postoperative period. Long-term follow-up data are also presented. PMID- 20589376 TI - Relevance of the anatomical location of the Adamkiewicz artery in spine surgery. AB - PURPOSE: The aim of this study was to describe the preoperative topography of the Adamkiewicz artery and the blood supply of the lumbosacral spinal cord in patients who underwent spinal surgery. The relevance for anterior approaches of the thoracolumbar spine was then analyzed. METHODS: One hundred consecutive spinal angiographies were reviewed. Surgical indications were: 26 vertebrectomies, 30 anterior fusions in fractures, 13 malunions, 16 anterior releases in scoliosis, 11 pedicle subtraction osteotomies and 4 thoracic disc hernias. The level and the side of the Adamkiewicz artery and the presence of additional radiculomedullary arteries were determined. Modifications of surgical planning owing to the Adamkiewicz artery were analyzed. RESULTS: The Adamkiewicz artery was always located between T8 and L3, at T9 or T10 in 50%, and coming from the left side in 75% of the cases. Additional radiculomedullary arteries were found in 43% of the cases. A concordance between the topography of the Adamkiewicz artery and the planned surgical approach was noted in 15%, which led to ten side changings and three modifications of surgical technique with segmental vessel preservation. An ischemic syndrome of the anterior spinal cord did not occur. CONCLUSIONS: Spinal cord ischemia is rarely reported after segmental vessel ligation. Spinal angiography allows determining the topography of the Adamkiewicz artery safely. If the planned surgical approach is located at the same level, a contralateral approach or selective surgical techniques without vessel ligation could avoid possible damage to the Adamkiewicz artery if the pathology does not dictate the side and the extent of the surgical approach. PMID- 20589378 TI - Isolation of the endosperm-specific LPAAT gene promoter from coconut (Cocos nucifera L.) and its functional analysis in transgenic rice plants. AB - As one of the key tropical crops, coconut (Cocos nucifera L.) is a member of the monocotyledonous family Aracaceae (Palmaceae). In this study, we amplified the upstream region of an endosperm-specific expression gene, Lysophosphatidyl acyltransferase (LPAAT), from the coconut genomic DNA by chromosome walking. In this sequence, we found several types of promoter-related elements including TATA box, CAAT-box and Skn1-motif. In order to further examine its function, three different 5'-deletion fragments were inserted into pBI101.3, a plant expression vector harboring the LPAAT upstream sequence, leading to pBI101.3-L1, pBI101.3-L2 and pBI101.3-L3, respectively. We obtained transgenic plants of rice by Agrobacterium-mediated callus transformation and plant regeneration and detected the expression of gus gene by histochemical staining and fluorometric determination. We found that gus gene driven by the three deletion fragments was specifically expressed in the endosperm of rice seeds, but not in the empty vector of pBI101.3 and other tissues. The highest expression level of GUS was at 15 DAF in pBI101.3-L3 and pBI101.3-L2 transgenic lines, while the same level was detected at 10 DAF in pBI101.3-L1. The expression driven by the whole fragment was up to 1.76- and 2.8-fold higher than those driven by the -817 bp and -453 bp upstream fragments, and 10.7-fold higher than that driven by the vector without the promoter. Taken together, our results strongly suggest that these promoter fragments from coconut have a significant potential in genetically improving endosperm in main crops. PMID- 20589379 TI - Early response assessment in patients with multiple myeloma during anti angiogenic therapy using arterial spin labelling: first clinical results. AB - OBJECTIVE: To determine if arterial-spin-labelling (ASL) MRI can reliably detect early response to anti-angiogenic therapy in patients with multiple myeloma by comparison with clinical/haematological response. METHODS: Nineteen consecutive patients (10 men; mean age 63.5 +/- 9.1 years) were included in the present study. Inclusion criteria were diagnosis of stage III multiple myeloma and clinical indication for therapeutical administration of bortezomib or lenalidomide. We performed MRI on 3.0T MR in the baseline setting, 3 weeks after onset of therapy and after 8 weeks. Clinical responses were determined on the basis of international uniform response criteria in correlation with haematological parameters and medium-term patient outcome. MRI studies were performed after approval by the local institutional review board. RESULTS: Fifteen patients responded to anti-myeloma therapy; 4/19 patients were non responders to therapy. Mean tumour perfusion assessed by ASL-MRI in a reference lesion was 220.7 +/- 132.5 ml min(-1) 100 g(-1) at baseline, and decreased to 125.7 +/- 86.3 (134.5 +/- 150.9) ml min(-1) 100 g(-1) 3 (8) weeks after onset of therapy (P < 0.02). The mean decrease in paraproteinaemia at week 3 (8) was 52.3 +/- 47.7% (58.2 +/- 58.7%), whereas beta2-microglobulinaemia decreased by 20.3 +/ 53.1% (23.3 +/- 57.0%). Correlation of ASL perfusion with outcome was significant (P = 0.0037). CONCLUSION: ASL tumour perfusion measurements are a valuable surrogate parameter for early assessment of response to novel anti angiogenic therapy. PMID- 20589377 TI - A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer. AB - PURPOSE: (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti EGFR treatment. METHODS: Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0 300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. RESULTS: Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. CONCLUSIONS: Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer. PMID- 20589380 TI - Diagnostic value of time-resolved CT angiography for the lower leg. AB - OBJECTIVE: The aim of this study was to test the feasibility of time-resolved computed tomography angiography (TR-CTA) for use in the lower leg. METHODS: Fifty nine patients with suspected peripheral arterial occlusive disease were examined with a standard CTA (S-CTA) of the lower run-off and with an additional TR-CTA of the calves (12 phases; 2.5 s/phase, 80 kV, 120 mAs, volume of contrast medium 50 mL, flow rate 5.0 mL/s). For seven lower-leg artery segments, arterial contrast and the presence of venous overlay were tested for S-CTA and TR-CTA. Stenoses were classified on a three-point scale separately for S-CTA and TR-CTA, and diagnostic confidence for stenosis assessment was evaluated for both datasets. Contrast arrival times and HU values were evaluated in patients with asymmetric proximal stenoses. RESULTS: TR-CTA resulted in significantly higher contrast enhancement (P < 0.0001) and less venous overlay as compared to S-CTA (P < 0.05). Diagnostic confidence for stenosis rating was significantly higher in TR-CTA (P < 0.0001). Asymmetric proximal stenoses lead to significantly delayed and diminished contrast enhancement on the stenotic side. CONCLUSION: TR-CTA of the calves is feasible and provides higher enhancement and higher diagnostic confidence as compared to monophasic CTA of the lower legs. PMID- 20589382 TI - Evaluating patients' outcome post-Kasai operation: a 19-year experience with modification of the hepatic portoenterostomy and applying a novel steroid therapy regimen. AB - BACKGROUND: We reported a modification of the hepatic portoenterostomy (HPE) for biliary atresia with favorable results. HPE is associated with a risk of hepatic impairment, so we adopted a novel steroid therapy regimen well suited to our procedure. This paper reports the results of our experience. PATIENTS AND METHODS: Between 1991 and 2009, 53 patients (18 boys, 35 girls) underwent modified HPE with novel steroid therapy, which consisted of administering hydrocortisone immediately after surgery, followed by intravenous administration of prednisolone. The number of patients who became normal total bilirubin (TB) levels, frequency of early onset cholangitis and other postoperative complications, and outcomes were retrospectively studied. RESULTS: The TB levels in 43 of the 53 patients became normal. Cholangitis was observed in seven, but all of them recovered. Other postoperative complications were noted in eight, but with no fatal cases. Of the 11 patients who underwent living-donor liver transplantation, 3 died after the transplant. Of the 53 patients, 39 are alive without liver transplantation and 34 have normal TB (range of observation period: 18 years and 9-2 months). CONCLUSIONS: The novel steroid regimen may have contributed to the outcome and appears to be well suited to the modified HPE. PMID- 20589381 TI - Our 10-year experience of variable Mullerian anomalies and its management. AB - PURPOSE: Though the Mullerian duct anomalies are rare in incidence, their variable age, and mode of presentation makes their management difficult. METHODS: In the last 10 years authors managed 14 patients with different types of Mullerian anomalies. There were eight patients with complete Mullerian agenesis: three of partial Mullerian agenesis, one patient had uterine didelphys with vertical and transverse vaginal septum on left side, one patient had uterine didelphys with cervical agenesis on the right side, one patient had MRKH with anorectal malformation. RESULTS: Patients with complete Mullerian agenesis underwent bowel vaginoplasty, and patients with partial Mullerian agenesis with hydrocolpos underwent pull-through vaginoplasty. Patient of uterine didelphys one with septum underwent septum excision and in another with cervical agenesis, cervix opened and drain kept. In MRKH with vestibular fistula, fistulous opening was kept as vaginal opening and rectum brought down as a neoanus. CONCLUSION: Mullerian duct anomalies can present in any age group and with variable symptoms. Sigmoid colon vaginoplasty is an excellent procedure for complete or partial Mullerian agenesis. Correct evaluation of these patients and proper management is a challenge. PMID- 20589383 TI - Treatment of a large thrombus containing lesion with the MGuard protective net coronary stent system: optical coherence tomographic evidence of complete plaque sealing. PMID- 20589384 TI - Heterotopic triplets: tubal ectopic and twin intrauterine pregnancy. A review of obstetric outcomes with a case report. AB - INTRODUCTION: Heterotopic triplets hardly take place, but nowadays the extended use of assisted reproductive technologies is increasing the ectopic pregnancies rate and subsequently the heterotopic pregnancies, leading to a potentially dangerous condition for the woman and the intrauterine pregnancy. MATERIAL AND METHODS: Fourteen cases previously reported in the literature of patients presenting an intrauterine twin pregnancy which became complicated by a tubal ectopic pregnancy have been reviewed. The case of a patient following a homologous intrauterine insemination treatment, resulting in live birth of both twins, is also described. CONCLUSION: Although the diagnosis of heterotopic triplets with tubal ectopic is challenging, a timely surgical treatment will preserve intrauterine gestation with a great chance of a successful obstetric outcome for both twins. PMID- 20589385 TI - A Japanese physician's experience as an obstetrics patient in the United States and Japan. PMID- 20589386 TI - Cellular proliferation in female pelvic organ prolapse: a pilot study. AB - PURPOSE: To assess cell proliferation in pelvic organ prolapse (POP). METHODS: Tissue samples of the anterior vaginal wall and uterosacral ligaments (USLs) were obtained from eight women with combined anterior vaginal wall and uterine prolapse and from eight women without POP in a standardized fashion. Immunohistochemistry against Ki-67 was used to assess cell proliferation in vaginal and USL biopsies. RESULTS: There were no significant differences in age, parity, menopausal status or hormone replacement therapy between the two groups. The POP-Q stage of uterine and anterior vaginal wall prolapse was significantly higher in the group of women with prolapse compared to the group without prolapse [median (range) 3 (3-4) vs. 0 (0), <0.01]. There was no significant difference between Ki-67 expressions in women with or without prolapse. CONCLUSION: There were no significant differences in cell proliferation between samples from women with or without POP. PMID- 20589387 TI - Ewing sarcoma-primitive neuroectodermal tumor of the uterus: a clinicopathologic, immunohistochemical and ultrastructural study of one case. AB - INTRODUCTION: Ewing sarcoma-primitive neuroectodermal tumors (ES/PNET) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiation. ES/PNET of the uterus is rare. There are 43 cases published in the English literature as far as we know. We describe an additional case. CASE REPORT: A 56-year-old woman presented with a 2-month history of irregular menopausal vaginal bleeding. After surgical excision, microscopic, immunohistochemical and electron microscopic examination suggested the diagnosis of ES/PNET. The patient underwent combined chemotherapy consisting of ifosfamide, etoposide, and cisplatin. She was alive with no evidence of recurrence or metastasis after 41 months of the initial operation. DISCUSSION: In spite of the rarity of ES/PNET, we should consider it in the differential diagnosis of small cell neoplasms of the uterus. PMID- 20589388 TI - Odor identification ability and self-reported upper respiratory symptoms in workers at the post-9/11 World Trade Center site. AB - Following the World Trade Center (WTC) collapse on September 11, 2001, more than 40,000 people were exposed to a complex mixture of inhalable nanoparticles and toxic chemicals. While many developed chronic respiratory symptoms, to what degree olfaction was compromised is unclear. A previous WTC Medical Monitoring and Treatment Program study found that olfactory and nasal trigeminal thresholds were altered by the toxic exposure, but not scores on a 20-odor smell identification test. OBJECTIVES: To employ a well-validated 40-item smell identification test to definitively establish whether the ability to identify odors is compromised in a cohort of WTC-exposed individuals and, if so, whether the degree of compromise is associated with self-reported severity of rhinitic symptoms. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 99 WTC-exposed persons and 99 matched normal controls. The Sino-Nasal Outcomes Test (SNOT-20) was administered to the 99 WTC exposed persons and compared to the UPSIT scores. RESULTS: The mean (SD) UPSIT scores were lower in the WTC-exposed group than in age-, sex-, and smoking history-matched controls [respective scores: 30.05 (5.08) vs 35.94 (3.76); p = 0.003], an effect present in a subgroup of 19 subjects additionally matched on occupation (p < 0.001). Fifteen percent of the exposed subjects had severe microsmia, but only 3% anosmia. SNOT-20 scores were unrelated to UPSIT scores (r = 0.20; p = 0.11). CONCLUSION: Exposure to WTC air pollution was associated with a decrement in the ability to identify odors, implying that such exposure had a greater influence on smell function than previously realized. PMID- 20589389 TI - Acute effects of supramaximal exercise on carotid artery compliance and pulse pressure in young men and women. AB - The purpose of this study was to determine the cumulative effects of repeated cycling sprints (Wingate tests) on carotid compliance and blood pressure (BP). Fourteen young, healthy men and women completed this study. Vascular and hemodynamic measurements were taken at rest, 5 min following a first Wingate test, 25 min following the first Wingate test, 5 min following a second Wingate test, and 25 min following the second Wingate test. At each time point, the measurements taken included brachial and carotid pulse pressure (PP), heart rate, carotid artery maximum and minimum diameters, and carotid compliance. Carotid BP was obtained with applanation tonometry. Carotid diameters were obtained using ultrasonography and compliance was calculated from carotid diameters and BP. Carotid and brachial PP increased significantly (P < 0.05) 5 min after each Wingate test and returned to near baseline 25 min after each Wingate test. No cumulative PP effects were seen. A cumulative effect was seen for carotid compliance: 5 min following the second sprint, carotid arterial compliance decreased significantly more than 5 min following the first sprint (P < 0.05). A single cycling sprint reduces carotid artery compliance immediately after exercise. Performance of a second identical cycling sprint further compounds this vascular change, reducing carotid artery compliance beyond levels seen following a single cycling sprint. PMID- 20589390 TI - Combined cycle and run performance is maximised when the cycle is completed at the highest sustainable intensity. AB - The aim of this study was to determine the effect of cycle intensity on subsequent running performance and combined cycle-run (CR) performance. Seven triathletes undertook a cycling graded exercise test to exhaustion, an isolated 500-kJ cycle time trial (CTT) and an isolated 5-km running time trial. Then they performed a series of CR tests, at various cycle intensities, followed by an all out, 5-km run. The CR tests were separated into four categories based on the percentage of the CTT at which the cycle was performed (CR 81-85%, CR 86-90%, CR 91-95%, and CR 96-100%). Running performance was slower during CR 96-100% compared to CR 81-85% and CR 86-90% (20:45 +/- 1:19 vs. 19:56 +/- 0:40 and 19:46 +/- 0:49 min; P < 0.05), but not CR 91-95% (20:19 +/- 1:08 min; P > 0.05). CR performance was maximised during CR 96-100% when compared to CR 81-85, CR 86-90 and CR 91-95% (56:37 +/- 4:04 vs. 62:40 +/- 5:30, 59:53 +/- 4:41 and 58:29 +/- 4:40 min; P < 0.05). The results suggest that combined cycle and run performance is maximised when the cycle is completed at the highest sustainable intensity. PMID- 20589391 TI - Differences in exercise limb blood flow and muscle deoxygenation with age: contributions to O2 uptake kinetics. AB - The adjustments of pulmonary oxygen uptake V O2p limb blood flow (LBF) and muscle deoxygenation (DeltaHHb) were examined during transitions to moderate-intensity, knee-extension exercise in seven older (OA; 71 +/- 7 year) and seven young (YA; 26 +/- 3 year) men. YA and OA performed repeated step transitions from an active baseline (3 W; 100 g) to a similar relative intensity of ~80% estimated lactate threshold (theta(L)), and YA also performed the same absolute work rate as the OA (24 W, 800 g). Breath-by-breath V O2p femoral artery LBF (Doppler ultrasound) and muscle HHb (near-infrared spectroscopy) were measured. Phase 2V O2p LBF, and DeltaHHb data were fit with a mono-exponential model. tau V O2p was greater in OA (58 +/- 21 s) than YA(80%) (31 +/- 9 s) and YA(24W) (29 +/- 11 s). The increase in LBF per increase in V O2p was not different between groups (5.3-5.8 L min( 1)/L min(-1)); however, the tauLBF was greater in OA (44 +/- 19 s) than YA(24W) (18 +/- 7 s). The overall adjustment in DeltaHHb (tau'DeltaHHb) was not different between OA and YA, but was faster than tau V O2p in OA. This faster tau'DeltaHHb than tau V O2p resulted in an "overshoot" of the normalized DeltaHHb/Delta V O2p response relative to the steady state level that was significantly greater in OA compared with YA suggesting that the adjustment of microvascular blood flow is slowed in OA thereby requiring a greater reliance on O(2) extraction during the transition to exercise. PMID- 20589392 TI - Reduction of adhesion formation by an angiotensin type 1 receptor antagonist. AB - PURPOSE: Adhesion formations are important causes of intestinal obstruction and can lead to infertility in women. The formation of adhesion appears to be determined by the fibrinolytic activity. Fibrinolysis itself is controlled by the plasminogen activator system, and several studies have shown that angiotensin type 1 (AT(1)) receptor antagonists can reduce plasminogen activator inhibitor-1 (PAI-1) expression, but the effect of AT(1) receptor antagonists on PAI-1 expression involved in the adhesion formation remains unclear. The aim of this study was to investigate whether an AT(1) antagonist, candesartan, can reduce PAI 1 mRNA expression using experimental model of peritoneal adhesions, which seems to reflect post-operative adhesions. METHODS: Using the experimental bowel adhesion rat model, we compared adhesion formation evaluated by the adhesion scoring system and PAI-1 mRNA expression. RESULTS: The adhesion score and PAI-1 mRNA expression were significantly increased in the experimental bowel adhesion rat model. Candesartan administration decreased adhesion score and abolished increase in PAI-1 mRNA expression. CONCLUSIONS: The AT(1) receptor antagonist, candesartan, significantly decreased the severity of intraperitoneal adhesion, which was associated with an inhibition of PAI-1 mRNA expression in the mesenterium of rats. It suggests that AT(1) receptor antagonists may be useful for the prevention of adhesion formation after surgery. PMID- 20589393 TI - Perforator vessel anatomy of the papilla umbilicalis: topography and importance for reconstructive abdominal wall surgery. AB - PURPOSE: Separation of midline abdominal wall components or other procedures involving the papilla umbilicalis within the context of abdominal wall reconstruction can significantly affect vasculature of the umbilicus. Adjusting dissection to the vascular anatomy of that region may evade such complications. For this purpose, an anatomic microdissection study was performed, focusing on the vascular architecture of the papilla umbilicalis in the midst of the stratigraphical anatomy of the midline abdominal wall. METHODS: Ramifications of the epigastric vessels were filled with dye on 27 abdominal walls originating from 15 female and 12 male corpses. Vascular architecture of the midline abdominal wall was examined by X-ray imaging and microdissection focusing region of the papilla umbilicalis. RESULTS: Vasculature of the papilla umbilicalis is provided by both myocutaneous and septocutaneous perforator vessels originating from the medial branch of the arteria epigastrica inferior and accompanying veins. On their way to the inferiolateral basis of the papilla umbilicalis, these perforators prove an intimate and regular association with the rectus abdominis muscle, and different components of the rectus sheath. CONCLUSIONS: Vasculature of the papilla umbilicalis is susceptible to damage resulting from separation of midline abdominal wall components or periumbilical dissections. To secure vasculature of the papilla umbilicalis, the integrity of the loose areolar fascia covering the posterior surface of the rectus abdominis muscle must be kept from being harmed by dissection. In addition, the musculo-fibrous-aponeurotic anatomy on either the left or the right side of the papilla umbilicalis must be left in structural continuity. PMID- 20589394 TI - Human errors in (inhuman?) triage. PMID- 20589395 TI - How does habitat complexity affect ant foraging success? A test using functional measures on three continents. AB - Habitat complexity can mediate key processes that structure local assemblages through effects on factors such as competition, predation and foraging behaviour. While most studies address assemblage responses to habitat complexity within one locality, a more global approach allows conclusions with greater independence from the phylogenetic constraints of the target assemblages, thus allowing greater generality. We tested the effects of natural and manipulated habitat complexities on ant assemblages from South Africa, Australia and Sweden, in order to determine if there were globally consistent responses in how functional measures of foraging success are regulated by habitat complexity. Specifically, we considered how habitat complexity affected ant foraging rates including the speed of discovery and rate of monopolisation. We also tested if habitat complexity affected the body size index, a size-related morphological trait, of ants discovering resources and occupying and monopolising the resources after 180 min. Ants were significantly slower to discover baits in the more complex treatments, consistent with predictions that they would move more slowly through more complex environments. The monopolisation index was also lower in the more complex treatments, suggesting that resources were more difficult to defend. Our index of ant body size showed trends in the predicted direction for complexity treatments. In addition, ants discovering, occupying and monopolising resources were smaller in simple than in complex natural habitats. Responses of discovering ants to resources in natural habitats were clear in only one of three regions. Consistent with our predictions, habitat complexity thus affected functional measures of the foraging success of ants in terms of measures of discovery and monopolisation rates and body size traits of successful ants. However, patterns were not always equally clear in manipulative and mensurative components of the study. PMID- 20589396 TI - Grazers and vitamins shape chain formation in a bloom-forming dinoflagellate, Cochlodinium polykrikoides. AB - Predators influence the phenotype of prey through both natural selection and induction. We investigated the effects of grazers and nutrients on chain formation in a dinoflagellate, Cochlodinium polykrikoides, which forms dense blooms and has deleterious effects on marine ecosystems around the world. Field populations of C. polykrikoides formed longer chains than laboratory cultures without grazers. In the field, chain length of C. polykrikoides was positively correlated with the abundance of the copepod Acartia tonsa. Chain length of C. polykrikoides increased when exposed to live females of A. tonsa or its fresh (<24 h post-isolation) exudates for 48 h. These results suggest that dissolved chemical cues released by A. tonsa induce chain formation in C. polykrikoides. Ingestion rate of A. tonsa on four-cell chains of C. polykrikoides was lower than on single cells, suggesting that chain formation may be an effective anti-grazing defense. Finally, nutrient amendment experiments demonstrated that vitamins (B(1), B(7), and B(12)) increased the chain length of C. polykrikoides both singly and collectively, while trace metals and inorganic nutrients did not, showing that vitamins may also influence chain formation in this species. PMID- 20589397 TI - Propionic acid fermentation by Propionibacterium freudenreichii CCTCC M207015 in a multi-point fibrous-bed bioreactor. AB - Propionic acid was produced in a multi-point fibrous-bed (MFB) bioreactor by Propionibacterium freudenreichii CCTCC M207015. The MFB bioreactor, comprising spiral cotton fiber packed in a modified 7.5-l bioreactor, was effective for cell immobilized propionic acid production compared with conventional free cell fermentation. Batch fermentations at various glucose concentrations were investigated in the MFB bioreactor. Based on analysis of the time course of production, a fed-batch strategy was applied for propionic acid production. The maximum propionic acid concentration was 67.05 g l(-1) after 496 h of fermentation, and the proportion of propionic acid to total organic acids was approximately 78.28% (w/w). The MFB bioreactor exhibited excellent production stability during batch fermentation and the propionic acid productivity remained high after 78 days of fermentation. PMID- 20589398 TI - Performance evaluation of the SITE(r) model to estimate energy flux in a tropical semi-deciduous forest of the southern Amazon Basin. AB - The SITE(r) model was originally developed to study the response of tropical ecosystems to varying environmental conditions. The present study evaluated the applicability of the SITE model to simulation of energy fluxes in a tropical semi deciduous forest of the southern Amazon Basin. The model was simulated with data representing the wet and dry season, and was calibrated according to each season. The output data of the calibrated model [net radiation (Rn), latent heat flux (LE) and sensible heat flux (H)] were compared with data observed in the field for validation. Considering changes in parameter calibration for a time step simulation of 30 min, the magnitude of variation in temporal flux was satisfactory when compared to observation field data. There was a tendency to underestimate and overestimate LE and H, respectively. Of all the calibration parameters, the soil moisture parameter presented the highest variation over the seasons, thus influencing SITE model performance. PMID- 20589399 TI - Regenerative medicine for insulin deficiency: creation of pancreatic islets and bioartificial pancreas. AB - Recent advances in pancreas organogenesis have greatly improved the understanding of cell lineage from inner cell mass to fully differentiated beta-cells. Based upon such knowledge, insulin-producing cells similar to beta-cells to a certain extent have been generated from various cell sources including embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells, although fully differentiated cells comparable to beta-cells are not yet available. The bioartificial pancreas is a therapeutic approach to enable allo- and xenotransplantation of islets without immune suppression. Among several types of bioartificial pancreases (BAPs), micro-encapsulated porcine islets are already in use in clinical trials and may, perhaps, replace islet transplantation in the near future. Some types of bioartificial pancreas such as macro-encapsulation are also useful for keeping transplanted cells enclosed in case retrieval is necessary. Therefore, early clinical applications of artificially generated beta like cells, especially those from ESCs or iPS cells, will be considered in combination with retrievable BAPs. PMID- 20589400 TI - The brain monitoring with Information Technology (BrainIT) collaborative network: EC feasibility study results and future direction. AB - BACKGROUND: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain-injured patients and to facilitate a more efficient infrastructure for assessing new health care technology with the primary objective of improving patient care. European Community (EC) funding supported meetings over a year to discuss and define a core dataset to be collected from patients with traumatic brain injury using IT-based methods. We now present the results of a subsequent EC-funded study with the aim of testing the feasibility of collecting this core dataset across a number of European sites and discuss the future direction of this research network. METHODS: Over a 3-year period, data collection client- and web-server-based tools were developed and core data (grouped into nine categories) were collected from 200 head-injured patients by local nursing staff in 22 European neuro-intensive care centres. Data were uploaded through the BrainIT website and random samples of received data were selected automatically by computer for validation by data validation staff against primary sources held in each local centre. Validated data were compared with originally transmitted data and percentage error rates calculated by data category. Feasibility was assessed in terms of the proportion of missing data, accuracy of data collected and limitations reported by users of the IT methods. FINDINGS: Thirteen percent of data files required cleaning. Thirty "one-off" demographic and clinical data elements had significant amounts of missing data (>15%). Validation staff conducted 19,461 comparisons between uploaded database data with local data sources and error rates were commonly less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Nearly 10,000 therapies were successfully recorded with start-times but approximately a third had inaccurate or missing "end-times" which limits the analysis of duration of therapy. Over 40,000 events and procedures were recorded but events with long durations (such as transfers) were more likely to have end-times missed. CONCLUSIONS: The BrainIT core dataset is a rich dataset for hypothesis generation and post hoc analyses, provided that studies avoid known limitations in the dataset. Limitations in the current IT-based data collection tools have been identified and have been addressed. In order for multi centre data collection projects to be viable, the resource intensive validation procedures will require a more automated process and this may include direct electronic access to hospital-based clinical data sources for both validation purposes and for minimising the duplication of data entry. This type of infrastructure may foster and facilitate the remote monitoring of patient management and protocol adherence in future trials of patient management and monitoring. PMID- 20589401 TI - The sutureless excimer laser assisted non-occlusive anastomosis (SELANA); a feasibility study in a pressurized cadaver model. AB - OBJECTIVE: To compare intracranial feasibility of the conventional Excimer laser assisted non-occlusive anastomosis (ELANA) with the new experimental sutureless ELANA (SELANA). METHODS: Four pressurized human cadaver heads were bilaterally trepanated, using a combined pterional/pretemporal/transcavernous approach. In each head, seven ELANA anastomoses and seven contralateral SELANA anastomoses were constructed on (1) the proximal PCA/basilar artery (P1 segment/basilar artery; BA), (2) the distal posterior cerebral artery (PCA, P2 segment), (3) the supraclinoidal internal carotid artery (ICA), (4) the ICA bifurcation, (5) the proximal anterior cerebral artery (ACA, A1 segment), (6) the proximal middle cerebral artery (MCA, M1 segment), and (7) the distal MCA (M2 segment). RESULTS: In total, 26 of 28 ELANA anastomoses (93%) and 22 of 28 SELANA anastomoses (79%) could be completed. Two ELANA anastomoses on the BA could not be finished because of limited space. Six SELANA anastomoses could not be attached because the applicator did not facilitate an angulated anastomosis spot. Of the remaining anastomoses, more ELANA (eight) than SELANA (two) anastomoses could not be realized without manipulation of surrounding structures. The SELANA anastomoses were completed significantly faster than the ELANA, mean difference ranging from 11 min on the M2 to 107 min on the P1/BA. CONCLUSION: This comparative study shows potential advantages of the SELANA anastomosis over the ELANA anastomosis because during application, it causes less manipulation of surrounding structures while it is faster and easier. Further preclinical research should be performed in order to improve SELANA feasibility on angulated anastomosis spots and to assess long-term SELANA patency and endothelialization. PMID- 20589402 TI - Expression and tissue and subcellular localization of anthocyanidin synthase (ANS) in grapevine. AB - Anthocyanidin synthase (ANS) is one of the key enzymes in the biosynthesis of both anthocyanins and proanthocyanidins in grapevine. Although substantial researches have investigated ANS gene expression and regulation at the transcriptional level, little is yet known about protein expression and distribution in grapevine. Here, the expression and tissue and subcellular localization of ANS in different Cabernet sauvignon grapevine tissues were investigated by using the techniques of Western blotting, immunohistochemical localization, immuno-electron microscopy, and confocal microscopy. The results showed that the ANS was expressed in the grape berries, leaves, stems, petioles, and leaf buds. In grape berry skin and flesh, ANS expression is developmental dependent. Immunohistochemical analysis revealed that ANS is primarily distributed in the exocarp, mesocarp, and seed of the fruit; in palisade and spongy tissues of the leaves; in the primary phloem and pith ray in the stems; and in the growth point and leaf primordium of the leaf buds. Furthermore, at the subcellular level, the ANS was mainly localized in the cytoplasm regardless of cell types and some ANS were also found in the nucleus in the mesocarp vascular bundle and leaf bud cells. This research will give further insight for the biosynthesis and regulation of different flavonoid compounds in grapevine. PMID- 20589403 TI - Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis. AB - Mechanical forces are essential to maintain skeletal integrity, and microgravity exposure leads to bone loss. The underlying molecular mechanisms leading to the changes in osteoblasts and osteoclast differentiation and function remain to be fully elucidated. Because of the infrequency of spaceflights and payload constraints, establishing in vitro and in vivo systems that mimic microgravity conditions becomes necessary. We have established a simulated microgravity (modeled microgravity, MMG) system to study the changes induced in osteoclast precursors. We observed that MMG, on its own, was unable to induce osteoclastogenesis of osteoclast precursors; however, 24 h of MMG activates osteoclastogenesis-related signaling molecules ERK, p38, PLCgamma2, and NFATc1. Receptor activator of NFkB ligand (RANKL) (with or without M-CSF) stimulation for 3-4 days in gravity of cells that had been exposed to MMG for 24 h enhanced the formation of very large tartrate-resistant acid phosphatase (TRAP)-positive multinucleated (>30 nuclei) osteoclasts accompanied by an upregulation of the osteoclast marker genes TRAP and cathepsin K. To validate the in vitro system, we studied the hindlimb unloading (HLU) system using BALB/c mice and observed a decrease in BMD of femurs and a loss of 3D microstructure of both cortical and trabecular bone as determined by micro-CT. There was a marked stimulation of osteoclastogenesis as determined by the total number of TRAP-positive multinucleated osteoclasts formed and also an increase in RANKL-stimulated osteoclastogenesis from precursors removed from the tibias of mice after 28 days of HLU. In contrast to earlier reported findings, we did not observe any histomorphometric changes in the bone formation parameters. Thus, the foregoing observations indicate that microgravity sensitizes osteoclast precursors for increased differentiation. The in vitro model system described here is potentially a valid system for testing drugs for preventing microgravity-induced bone loss by targeting the molecular events occurring in microgravity-induced enhanced osteoclastogenesis. PMID- 20589404 TI - Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial. AB - The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4 J/cm(2) per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7 days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients' sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer's and diode laser's mean scores (ANOVA, p < 0.05). The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7 days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments (p > 0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity. PMID- 20589405 TI - Simultaneous bilateral spontaneous pneumothorax following high-dose chemotherapy and bone marrow transplantation for mantle cell lymphoma without evidence of pulmonary disease. AB - Simultaneous bilateral spontaneous pneumothorax (SBSP) during high-dose chemotherapy has been described in patients with pulmonary involvement by malignancy, including sarcoma, trophoblastic tumor, non-seminomatous testicular cancer, and non-Hodgkin lymphoma. We present a case of SBSP developing in a patient 11 days after a high-dose chemotherapy preparative regimen and stem cell transplantation without underlying pulmonary disease or evidence of lung lesions. It is important to recognize spontaneous pneumothorax as a potential complication of high-dose chemotherapy, especially in patients with known pulmonary lesions. PMID- 20589406 TI - Effects of hemodialysis period on levels of blood trace elements and oxidative stress. AB - INTRODUCTION: As a treatment method for chronic renal failure (CRF), hemodialysis (HD) alters inorganic components containing trace elements. It was shown that decreased renal function is accompanied by insufficient antioxidant systems and/or increased free oxygen radicals. In this study, we aimed to investigate the effects of HD on trace element levels and oxidative stress markers. METHODS: We included 111 CRF patients on HD treatment three times a week and 24 healthy controls. Patients were divided into four groups according to HD duration. Plasma malondialdehyde (MDA), protein carbonyls and total sulfhydryl (-SH) levels, zinc (Zn), copper (Cu), and magnesium (Mg) levels, and erythrocyte superoxide dismutase (SOD) activity were measured from blood taken from patients before HD. RESULTS: SH levels and SOD activity in all groups were significantly lower than those in the control group (p < 0.001). All groups had significantly higher plasma MDA levels than did controls (p < 0.001). Whereas there was no significant difference in -SH levels and SOD activity between groups, increased periods of HD were associated with increases in MDA. MDA levels of the third and fourth groups were significantly higher than in the first and second groups (p < 0.05, p < 0.001, respectively). There was no significant difference of Zn, Cu, Mg, and protein carbonyl levels in and between all groups. However, plasma Cu levels and MDA concentrations were correlated (r = 0.26, p < 0.01). CONCLUSION: Prolonged exposure to HD can cause increased oxidative damage but has no effect on trace element concentration. PMID- 20589407 TI - Incidence of symptomatic stroke and cancer in chronic kidney disease patients treated with epoetins. AB - BACKGROUND: Use of erythropoiesis-stimulating agents (ESA) has been reported to increase the incidence of cardiovascular diseases at target Hb levels by more than 12.0 g/dl. The recent TREAT study found an increased incidence of stroke and cancer when maintaining the Hb level at 12.5 g/dl in diabetic patients. METHODS: Surveillance of Epoetin-Adverse Events of Stroke and Cancer (SEASCAN) was a cross sectional study conducted under urgent conditions by the Committee on CKD Initiatives of the Japanese Society of Nephrology. Patients who were at least 18 years old and had CKD stage 4 and 5, namely, eGFR <30 ml/min/1.73 m(2), and who had visited the outpatient department of the participating facilities between December 2009 and January 2010 with at least 6 months of prior medical treatment in the participating facilities were eligible to participate in the study. RESULTS: Of 7,415 patients with CKD stage 4 and 5, 3,653 (49.3%), 879 (11.9%) and 2,883 (38.9%) patients received no epoetin, epoetin for less than 6 months and epoetin for at least 6 months, respectively. In patients who did not use epoetin, use of epoetin for less than 6 months and use of epoetin for at least 6 months, the numbers of patients with stroke were 38 (1.0%), 8 (0.9%) and 27 (0.9%), respectively, and those with newly diagnosed or exacerbated malignancy were 88 (2.4%), 30 (3.4%) and 71 (2.5%), respectively, demonstrating insignificant associations between outcome and duration of treatment with epoetin (P for trend = 0.666 in stroke and 0.836 in malignancy). CONCLUSIONS: No significant increase in the risk of developing symptomatic stroke and cancer was observed for the use of epoetin in current clinical practice in Japan. PMID- 20589408 TI - Models of cardiac electromechanics based on individual hearts imaging data: image based electromechanical models of the heart. AB - Current multi-scale computational models of ventricular electromechanics describe the full process of cardiac contraction on both the micro- and macro- scales including: the depolarization of cardiac cells, the release of calcium from intracellular stores, tension generation by cardiac myofilaments, and mechanical contraction of the whole heart. Such models are used to reveal basic mechanisms of cardiac contraction as well as the mechanisms of cardiac dysfunction in disease conditions. In this paper, we present a methodology to construct finite element electromechanical models of ventricular contraction with anatomically accurate ventricular geometry based on magnetic resonance and diffusion tensor magnetic resonance imaging of the heart. The electromechanical model couples detailed representations of the cardiac cell membrane, cardiac myofilament dynamics, electrical impulse propagation, ventricular contraction, and circulation to simulate the electrical and mechanical activity of the ventricles. The utility of the model is demonstrated in an example simulation of contraction during sinus rhythm using a model of the normal canine ventricles. PMID- 20589409 TI - Chloroplasts can move in any direction to avoid strong light. AB - Chloroplasts migrate in response to different light intensities. Under weak light, chloroplasts gather at an illuminated area to maximize light absorption and photosynthesis rates (the accumulation response). In contrast, chloroplasts escape from strong light to avoid photodamage (the avoidance response). Photoreceptors involved in these phenomena have been identified in Arabidopsis thaliana and Adiantum capillus-veneris. Chloroplast behavior has been studied in detail during the accumulation response, but not for the avoidance response. Hence, we analyzed the chloroplast avoidance response in detail using dark adapted Adiantum capillus-veneris gametophyte cells and partial cell irradiation with a microbeam of blue light. Chloroplasts escaped from an irradiated spot. Both duration of this response and the distance of the migrated chloroplasts were proportional to the total fluence irradiated. The speed of movement during the avoidance response was dependent on the fluence rate, but the speed of the accumulation response towards the microbeam from cell periphery was constant irrespective of fluence rate. When a chloroplast was only partially irradiated with a strong microbeam, it moved away towards the non-irradiated region within a few minutes. During this avoidance response two additional microbeam irradiations were applied to different locus of the same chloroplast. Under these conditions the chloroplast changed the moving direction after a lag time of a few minutes without rolling. Taken together, these findings indicate that chloroplasts can move in any direction and never have an intrinsic polarity. Similar phenomenon was observed in chloroplasts of Arabidopsis thaliana palisade cells. PMID- 20589410 TI - Risk of mental disorders in family reunification migrants and native Danes: a register-based historically prospective cohort study. AB - OBJECTIVES: Although family reunification migrants form a large proportion of migrants, their prevalence of mental disorders is unknown because research has focused on mixed groups of first generation immigrants and refugees. Our aim was to investigate the risk of mental disorders among family reunification migrants compared with that among native Danes. METHODS: Family reunification migrants (n = 31,923) were matched on age and sex with native Danes (n = 127,687). Civil registration numbers were linked to the Danish Psychiatric Central Register to obtain data on diagnosis for all first-time psychiatric hospital contacts for migrants (n = 972) and native Danes (n = 5,390) between 1 January 1994 and 31 December 2003. RESULTS: Overall family reunification migrants had a significantly lower risk of having a first-time psychiatric contact for mental disorders than did native Danes (RR = 0.78; 95% CI 0.71-0.87); specific risks of psychotic, affective and neurotic disorders did not differ except for migrant men, who had a higher risk of nervous disorder than that of native Danes (RR = 1.59; 95% CI 1.17; 2.17). CONCLUSIONS: Overall, family reunification migrants had a similar or lower risk of mental disorders compared with native Danes. The results may reflect true morbidity patterns or an underestimation of mental illness due to problems of access to care. PMID- 20589411 TI - The determinants of sexually transmitted infections among reproductive age women in St. Petersburg, Estonia and Finland. AB - OBJECTIVES: Sexually transmitted infections' (STIs) rate vary in St. Petersburg, Estonia and Finland; the aim was to compare the determinants of self-reported sexually transmitted infections in these areas. METHODS: Data from four population-based questionnaire surveys were used (Finland in 1992 and 1999; St. Petersburg in 2003; Estonia in 2004). With the exception of the 1992 Finnish survey (interview) all were postal surveys, with 1,070 respondents in Finland (78 and 52% response rates), 1,147 (68%) in St. Petersburg, and 5,190 (54%) in Estonia. RESULTS: Risky sexual behaviours were equally common in the three areas and the determinants were the same. Women with an STIs history more often had had their first sexual intercourse when aged under 18, had not used condom during first intercourse, had a high number of lifetime or previous year sexual partners. However, marital status and education were not similar determinants. Cohabiting and well-educated women in Finland were more likely to have STIs while in other areas the associations found were not statistically significant. CONCLUSIONS: Risky behaviour predicts STIs, but does not explain the varying rates of STIs between areas. PMID- 20589412 TI - Fed-batch production of a bioflocculant from Corynebacterium glutamicum. AB - The constant-rate fed-batch production of the polygalacturonic acid bioflocculant REA-11 was studied. A controlled sucrose-feeding strategy resulted in a slight improvement in biomass and a 7% reduction in flocculating activity compared with the batch process. When fed with a 3 g l(-1) urea solution, the flocculating activity was enhanced to 720 U ml(-1) in 36 h. High cell density (2.12 g l(-1)) and flocculating activity (820 U ml(-1)) were obtained in a 10-l fermentor by feeding with a sucrose-urea solution, with values of nearly two times and 50% higher than those of the batch process, respectively. Moreover, the residual sucrose declined to 2.4 g l(-1), and residual urea decreased to 0.03 g l(-1). Even higher flocculating activity of 920 U ml(-1) and biomass of 3.26 g l(-1) were obtained by feeding with a sucrose-urea solution in a pilot scale fermentation process, indicating the potential industrial utility of this constant-rate feeding strategy in bioflocculant production by Corynebacterium glutamicum. PMID- 20589414 TI - The effect of divalent cations on the catalytic activity of the human plasma 3' exonuclease. AB - The 3'-exonuclease from human plasma is a soluble form of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) (EC 3.1.4.1/EC 3.6.1.9). Here, the possibility of divalent cation influence for the 3'-exonuclease activity was investigated using the phosphorothioate congener of oligonucleotide containing all phosphorothioate internucleotide linkages of the [R(P)]-configuration ([R(P) PS]-d[T(12)]) as the substrate for this enzyme. It was found that the 3' exonuclease is a metalloenzyme, i.e. its phosphodiesterase activity was completely abolished at 0.8 mM concentration EDTA and, in turn, it was restored in the presence of Mg(2+) or Mn(2+) ions. In addition, Mg(2+) can be replaced effectively by Ca(2+), Mn(2+), or Co(2+), but not by Ni(2+) and Cd(2+) during the hydrolysis of the phosphorothioate substrate in human plasma. In addition, the mechanism is postulated, by which a single internucleotide phosphorothioate bond of the S(P)-configuration at the 3'-end of unmodified phosphodiesters (PO oligos), or their phosporothioate analogs (PS-oligos) protects these compounds against degradation in blood. PMID- 20589415 TI - The impact of urban land expansion on soil quality in rapidly urbanizing regions in China: Kunshan as a case study. AB - At a stage of rapid economic development and urbanization in China, most cities are faced with serious problems caused by environment deterioration such as pollution, space press, afforestation degradation, and disordering. Kunshan City, one of the most economically vigorous regions in China, has suffered a more prominent conflict between urbanization and environmental safety. In this paper, urban land expansion in Kunshan City in the Yangtze River Delta was measured with reference to the Landsat data recorded in 1982, 1991, 1995, and 2003 and change in land-use pattern in 1981, 1991, 1995, and 2004 as well as that in nutrients in soils of different purposes between the periods were analyzed to study the effect of urban land-use expansion on soil characteristics. To get a better understanding of soil nutrients, heavy metal content, and pollution, on-the-spot investigation, sampling and laboratory analysis were all conducted, and the geo accumulation factors and revised Nemerow comprehensive index method were adopted for evaluation of the findings. The results show that the content of organic matter, total nitrogen, rapidly available nitrogen, and available phosphorus in the soil (except available potassium) all increased, and the average content of As, Cd, Cr, Cu, Pb, Ni, Hg, Se, and Zn prove to be 8.61, 0.12, 83.53, 32.49, 29.93, 30.45, 0.27, 0.24, and 93.3 mg kg(-1), respectively, showing degradation in soil quality. PMID- 20589416 TI - Co-feeding as a route for transmission of Rickettsia conorii israelensis between Rhipicephalus sanguineus ticks. AB - Rickettsia conorii is widely distributed in Europe, Asia, and Africa. The brown dog tick, Rhipicephalus sanguineus, is the recognized vector of R. conorii. In this study, we assessed the efficiency of R. conorii israelensis transmission between co-feeding Rh. sanguineus ticks. Infected Rh. sanguineus adults and uninfected nymphs were fed simultaneously upon either naive dogs or a dog previously exposed to this agent. When ticks were placed upon naive dogs, 92-100% of nymphs acquired the infection and 80-88% of infected engorged nymphs transmitted it transstadially. When ticks were placed upon a seropositive dog, only 8-28.5% of recipient nymphs became infected. Our results establish the first evidence for efficient natural transmission of R. conorii israelensis between co feeding ticks upon both naive and seropositive dogs. This route of transmission can ensure continuous circulation of R. conorii israelensis in tick vectors even in the absence of naive reservoir hosts. PMID- 20589417 TI - Response of Epilachna paenulata to two flavonoids, pinocembrin and quercetin, in a comparative study. AB - We examined the effects of the flavonoids pinocembrin and quercetin on the feeding behavior, survival, and development of the Cucurbitaceae pest Epilachna paenulata (Coleoptera: Coccinellidae). In no-choice experiments, 48 hr consumption of Cucurbita maxima Duch. leaves treated with pinocembrin at 1, 5, and 50 microg/cm(2) was less than one third of that for leaves treated with 0.1 microg/cm(2) of pinocembrin or untreated leaves. Larvae stopped feeding after 9 days of high doses of pinocembrin (5 and 50 microg/cm(2)), and larval weight and survival were negatively affected by pinocembrin at 1-50 microg/cm(2). Delayed mortality in comparison to food-deprived larvae suggests that the mechanism of action for pinocembrin is chronic intoxication, rather than simple starvation from antifeedant effects. In contrast, leaf consumption and larval weight were not significantly affected by quercetin (at 0.1, 1, 5, and 50 microg/cm(2)) while mortality rates were only slightly increased. The response of E. paenulata larvae in a choice-test to combinations of pinocembrin at antifeedant doses (5 and 50 microg/cm(2)) and quercetin at phagostimulant doses (0.01 and 0.1 microg/cm(2)) indicated that the feeding deterrent activity of the former completely overshadowed the stimulant activity of the latter. These results demonstrate the different responses of one insect species to two widely distributed plant flavonoids. Pinocembrin strongly affected survival of E. paenulata while quercetin had only a weak effect without major consequences on the insect life cycle. PMID- 20589418 TI - New types of flavonol oligoglycosides accumulate in the hemolymph of birch feeding sawfly larvae. AB - Larvae of nine species of sawflies (Symphyta) were fed with the foliage of three birch species, after which the larval hemolymph composition was studied by HPLC DAD and HPLC-ESI-MS. The hemolymph of sawfly larvae contained high concentrations of flavonol oligoglycosides (tri-, tetra-, penta-, and hexaglycosides) that could not be found in the larval foliar diet. In addition, there were significant between-sawfly species differences in both flavonoid composition and concentration (from 0.6 to 12.3 mg/ml) of the hemolymph. This suggested that the studied species have different biosynthetic activities for the synthesis of flavonoid oligoglycosides. Variation in the foliar diets did not cause differences in the hemolymph composition. Our hypothesis is that sawflies use foliar flavonoid monoglycosides rather than flavonoid aglycones to produce these new types of oligoglycosides. These findings open up new possibilities for understanding the more holistic role of flavonoids in insect biochemistry and complex interactions between plants and herbivores. PMID- 20589419 TI - Binding specificity of recombinant odorant-binding protein isoforms is driven by phosphorylation. AB - Native porcine odorant-binding protein (OBP) bears eleven sites of phosphorylation, which are not always occupied in the molecular population, suggesting that different isoforms could co-exist in animal tissues. As phosphorylation is a dynamic process resulting in temporary conformational changes that regulate the function of target proteins, we investigated the possibility that OBP isoforms could display different binding affinities to biologically relevant ligands. The availability of recombinant proteins is of particular interest for the study of protein/ligand structure-function relationships, but prokaryotic expression systems do not perform eukaryotic post translational modifications. To investigate the role of phosphorylation in the binding capacities of OBP isoforms, we produced recombinant porcine OBP in two eukaryotic systems, the yeast, Pichia pastoris, and the mammalian CHO cell line. Isoforms were separated by anion exchange HPLC, and their phosphorylation sites were mapped by MALDI-TOF mass spectrometry and compared to those of the native protein. Binding experiments with ligands of biological relevance in the pig, Sus scrofa, were performed by fluorescence spectroscopy on two isoforms of recombinant OBP expressed in the yeast. The two isoforms, differing only by their phosphorylation pattern, displayed different binding properties, suggesting that binding specificity is driven by phosphorylation. PMID- 20589420 TI - Molecular mechanism of NLRP3 inflammasome activation. AB - The inflammasome is an intracellular multimolecular complex that controls caspase 1 activity in the innate immune system. NLRP3, a member of the NLR family of cytosolic pattern recognition receptors, along with the adaptor protein ASC, mediates caspase-1 activation via assembly of the inflammasome in response to various pathogen-derived factors as well as danger-associated molecules. The active NLRP3 inflammasome drives innate immune response towards invading pathogens and cellular damage, and regulates adaptive immune response. Here, we review identified agonists of the NLRP3 inflammasome and the molecular mechanism by which they induce NLRP3 inflammasome activation. Three signaling pathways involving potassium efflux, generation of reactive oxygen species, and cathepsin B release are discussed. PMID- 20589421 TI - Dickkopf-1 as potential biomarker to evaluate bone erosion in systemic lupus erythematosus. AB - OBJECTIVE: This study aims to explore the potential role of circulating Dickkopf 1 (Dkk-1) and osteoprotegerin (OPG) in evaluating erosive arthritis in systemic lupus erythematosus (SLE). METHODS: Serum Dkk-1 and OPG levels were examined in 130 SLE patients including eight with erosive arthritis, 100 rheumatoid arthritis (RA) patients and 50 healthy individuals by ELISA. Comparison of serum Dkk-1 levels with presence of anti-cyclic citrullinated peptides (CCP) antibodies in evaluating erosive arthritis in SLE was carried out. Associations of Dkk-1 and OPG levels with results of clinical examination were also noted. RESULTS: Dkk-1 levels were significantly increased in eight SLE patients with erosive arthritis, compared to 58 SLE patients with non-erosive arthritis, 64 SLE patients without arthritis, and healthy controls, while similar with RA. In contrast, no significant changes of OPG levels were found except for higher levels in RA. No differences were found in Dkk-1 levels of SLE patients with erosive arthritis subdivided according to presence or absence of anti-CCP antibodies. Moreover, higher levels of Dkk-1 were identified in anti-CCP positive SLE patients with erosive arthritis compared to those with non-erosive arthritis or without arthritis. However, no significant correlations between Dkk-1 and OPG levels or between Dkk-1 levels and other laboratory and clinical manifestations were observed. CONCLUSIONS: High levels of circulating Dkk-1 were associated with bone erosion in patients with SLE, even when anti-CCP antibodies were absent. PMID- 20589422 TI - Subversion of innate immune signaling through molecular mimicry. AB - Innate immune signaling is mediated by a number of membrane-anchored or cytosolic receptor or sensor molecules. Several receptor families utilize conserved signaling domains such as the Toll/interleukin-1 receptor (TIR) domain and Pyrin domain (PYD) to link microbe recognition to induction of proinflammatory cytokines and interferons. Recent studies have identified a number of bacterial and viral TIR domains and PYD domains that directly target the signaling function of their host homologues. Emerging biochemical and structural studies of these microbial TIR and PYD domains suggest that they are mimics of their host counterparts at the sequence and structure levels. Unraveling the mechanisms of such molecular mimicry is crucial to our understanding and clinical intervention of infectious diseases and inflammatory disorders. PMID- 20589423 TI - Cardioprotection in the clinical setting. AB - Reperfusion therapy is the primary treatment of acute myocardial infarction and must be applied as soon as possible to limit the ischemic insult. Unfortunately, reperfusion is responsible for additional myocardial damage likely involving opening of the mitochondrial permeability transition pore. Ischemic postconditioning is a powerful intervention that dramatically reduces lethal reperfusion injury. Several clinical studies using angioplasty postconditioning now support its protective effects in patients with an acute myocardial infarction. Alternatively, pharmacological postconditioning could afford comparable protection and be applied to a much larger number of patients. Indeed, the mitochondrial permeability transition pore inhibitor cyclosporine A has been shown to generate a similar protection in acute myocardial infarction patients. Future large-scale trials are needed to determine whether angioplasty or pharmacological postconditioning may improve clinical outcome in STEMI patients. PMID- 20589424 TI - The extra 16-amino-acid peptide at C-terminal NS2 of the hypervirulent type-2 bovine viral diarrhea viruses has no effect on viral replication and NS2-3 processing of type-1 virus. AB - Bovine viral diarrhea virus (BVDV) is an economically important cattle pathogen with worldwide distribution. Besides the segregation of noncytopathic and cytopathic (CP) biotypes, BVDV exists as two genotypes. Both genotypes cause similar disease, and the majority of type-2 BVDV (BVDV-2) is no more virulent than type-1 viruses (BVDV-1). However, some BVDV-2 viruses are hypervirulent and causative reagents of a lethal disease called severe acute bovine viral diarrhea. Amino acid (aa) sequence analysis shows that the majority of hypervirulent BVDV-2 isolates contains an extra 16 aa peptide (-SSCPVPFDPSCHCNYF-) at C-terminal NS2 region. In this study, we investigated the flexibility of the corresponding NS2 region of BVDV-1 for tolerance of this peptide insertion and its effect on viral pathogenicity. Based on an infectious cDNA clone of BVDV-1 SD-1, a cDNA clone called pASD1-IN was constructed with insertion of the 16 aa peptide in the corresponding NS2 site. In vitro transcription and transfection of Madin-Darby bovine kidney (MDBK) cells resulted in the generation of infectious chimeric virus termed ASD1-IN. ASD1-IN does not show CP effect on MDBK cells and is similar to ASD1 in viral growth. Furthermore, ASD1-IN shows an NS2-3 processing pattern similar to ASD1. These results reveal that insertion of the 16 aa peptide at C-terminal NS2 of BVDV-1, at least for SD-1, has no effect on viral replication and NS2-3 processing in MDBK cells. PMID- 20589425 TI - Stem cell factor/c-Kit signaling in in vitro cultures supports early mouse embryonic development by accelerating proliferation via a mechanism involving Akt downstream genes. AB - PURPOSE: stem cell factor (SCF)/c-Kit regulates the proliferation and survival of germ cells or stem cells; however, little is known about the role of SCF/c-Kit in pre-implantation embryo development. METHODS: using exogenous SCF supplementation and c-Kit siRNA injection, we investigated the role and mechanism of SCF/c-Kit in pre-implantation mouse embryos. RESULTS: addition of soluble SCF to the culture medium improved blastocyst formation. c-Kit gene silencing reduced the rate of blastocyst formation and delayed embryonic development. The number of proliferating cells in c-Kit gene-silenced blastocysts decreased, whereas the number of apoptotic cells in blastocysts obtained from both experimental and the control groups was not affected. RT-PCR, immunostaining and western blotting revealed that proliferation-related Akt downstream targets were substantially affected by c-Kit gene silencing. CONCLUSION: SCF/c-Kit signaling through Akt downstream targets is likely involved in mediating the cleavage and proliferation of blastomeres during mouse pre-implantation embryogenesis. PMID- 20589426 TI - Wnt3a promotes hippocampal neurogenesis by shortening cell cycle duration of neural progenitor cells. AB - The effects of Wnt signaling on neural progenitor cells have been controversial. Activation of the canonical Wnt signaling pathway either promotes neural progenitor cell proliferation or accelerates their differentiation into postmitotic neurons. This study demonstrates that activation of the Wnt signaling pathway by itself induces neural progenitor cell proliferation but does not directly affect neuronal differentiation processes. To investigate whether Wnt signaling promotes expansion and/or differentiation of neural progenitor cells in the developing hippocampus, we prepared primary mouse hippocampal progenitors and treated them with Wnt3a in a chemically defined culture medium. Wnt3a increased the total number of cells, including the numbers of Ki67(+) proliferating cells and Tuj1(+) differentiated neurons. This result verified that Wnt3a promoted neural progenitor cell proliferation. Meanwhile, Wnt3a did not appear to actively enhance the neuronal differentiation process itself, because (1) the ratio of Tuj1(+) cells to the total cells, and (2) the ratio of BrdU(+) Tuj1(+) cells to the total BrdU(+) cells, were both comparable between cultures with or without Wnt3a. Indeed, Wnt3a caused no significant change in either cell survival or the proportion of symmetric and asymmetric cell divisions that directly affected neuron production. We finally demonstrated that the Wnt3a treatment simply shortened cell cycle duration of neural progenitor cells by 2.9 h. The accelerated cell cycle progression without affecting the ratio of symmetric/asymmetric cell divisions explains how Wnt signaling per se leads to the expansion of both proliferative cell population and differentiated neuronal cell population. PMID- 20589427 TI - Analysis of developmental gene conservation in the Actinomycetales using DNA/DNA microarray comparisons. AB - Based on available genome sequences, Actinomycetales show significant gene synteny across a wide range of species and genera. In addition, many genera show varying degrees of complex morphological development. Using the presence of gene synteny as a basis, it is clear that an analysis of gene conservation across the Streptomyces and various other Actinomycetales will provide information on both the importance of genes and gene clusters and the evolution of morphogenesis in these bacteria. Genome sequencing, although becoming cheaper, is still relatively expensive for comparing large numbers of strains. Thus, a heterologous DNA/DNA microarray hybridization dataset based on a Streptomyces coelicolor microarray allows a cheaper and greater depth of analysis of gene conservation. This study, using both bioinformatical and microarray approaches, was able to classify genes previously identified as involved in morphogenesis in Streptomyces into various subgroups in terms of conservation across species and genera. This will allow the targeting of genes for further study based on their importance at the species level and at higher evolutionary levels. PMID- 20589428 TI - Psychometric properties of the parent and teacher versions of the strengths and difficulties questionnaire for 4- to 12-year-olds: a review. AB - Since its development, the Strengths and Difficulties Questionnaire (SDQ) has been widely used in both research and practice. The SDQ screens for positive and negative psychological attributes. This review aims to provide an overview of the psychometric properties of the SDQ for 4- to 12-year-olds. Results from 48 studies (N = 131,223) on reliability and validity of the parent and teacher SDQ are summarized quantitatively and descriptively. Internal consistency, test retest reliability, and inter-rater agreement are satisfactory for the parent and teacher versions. At subscale level, the reliability of the teacher version seemed stronger compared to that of the parent version. Concerning validity, 15 out of 18 studies confirmed the five-factor structure. Correlations with other measures of psychopathology as well as the screening ability of the SDQ are sufficient. This review shows that the psychometric properties of the SDQ are strong, particularly for the teacher version. For practice, this implies that the use of the SDQ as a screening instrument should be continued. Longitudinal research studies should investigate predictive validity. For both practice and research, we emphasize the use of a multi-informant approach. PMID- 20589429 TI - Recovery-oriented training and staff attitudes over time in two state hospitals. AB - Recovery attitudes and concepts are often promoted to community mental health staff through educational and in-service trainings, but no study found has examined this in state hospitals. The current observational study aimed to examine the types of recovery-oriented trainings that occurred at two state hospitals over 1 year and subsequent changes in staff recovery attitudes. A total of 184 state hospital staff completed questionnaires assessing their personal optimism, consumer optimism, and agency recovery orientation at baseline and 1 year later. The types of recovery-oriented trainings staff received were categorized as general/inspirational or specific/practical training. Results found that the majority of staff at the two state hospitals received some recovery-oriented training, mostly general/inspirational training. Staff who received specific/practical training had a greater increase in agency recovery attitudes than staff who received only general/inspirational training or no training. However, the more trainings staff had, the higher their consumer optimism. These results suggest state hospitals are incorporating recovery oriented staff trainings, but more specific trainings may be needed and all staff involved in different levels of care need to be included. PMID- 20589430 TI - The role of antibody in Korean word recognition. AB - A subsyllabic phonological unit, the antibody, has received little attention as a potential fundamental processing unit in word recognition. The psychological reality of the antibody in Korean recognition was investigated by looking at the performance of subjects presented with nonwords and words in the lexical decision task. In Experiment 1, the nonwords with a high-frequency antibody were processed more slowly than those with a low-frequency antibody. Experiment 2 showed that separating the antibody unit is advantageous in processing certain types of Korean words. These results indicate that the antibody is a part of the lexical representation system and is a fundamental unit of lexical processing. PMID- 20589431 TI - Prognostic value of dobutamine stress echocardiography in octogenarians. AB - The prognostic value of dobutamine stress echocardiography (DSE) for risk stratification of patients aged >= 80 years is not clearly defined. A follow-up of 3 +/- 2 years for major cardiac events and all-cause mortality was obtained in 227 patients, age >= 80 years, who underwent DSE for known or suspected coronary artery disease. Stress function index (SFI), calculated as the ratio of peak wall motion score index to left ventricular ejection fraction, was analyzed both as continuous variable and categorized using the mean value of 5 as the cut-off. Only 95 patients (42%) of this group underwent a cycloergometer exercise stress test (EST). During DSE 118 patients developed inducible ischemia; SFI was 4.9 +/- 2.6 and 60 subjects showed a value higher than 5. EST gave a positive result in 12 patients and a negative result in 8 patients; it was inconclusive for inadequate increase in heart rate in 75 (79%) subjects. Advanced age (HR: 1.184/year, 95% CI: 1.073-1.306, p = 0.001) and SFI >= 5 (HR: 2.682, 95% CI: 1.429-5.035, p = 0.002) were independent predictors of all-cause mortality; advanced age (HR: 1.252/year, 95% CI: 1.064-1.473, p = 0.007), SFI >= 5 (HR: 3.181, 95% CI: 1.174-8.621, p = 0.02) and presence of left bundle branch block (HR: 3.060, 95% CI: 1.057-8.862, p = 0.039) independently predicted an increased occurrence of major cardiac events. No parameter derived from EST showed an independent prognostic role. DSE showed a significant prognostic value in octogenarians, both for all-cause mortality and major cardiac events. PMID- 20589432 TI - The national DBS brain tissue network pilot study: need for more tissue and more standardization. AB - Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval. PMID- 20589433 TI - Jun activation domain binding protein 1 is overexpressed from the very early stages of hepatocarcinogenesis. AB - BACKGROUND: As is known for many types of human cancers, the hepatocellular carcinoma (HCC) associated with chronic liver disease shows an obvious multistage process of tumor progression. Despite the demonstrated importance of cell-cycle regulators in tumor biology, there have only been a few studies of their role in multistep hepatocarcinogenesis. Recently, we reported that a high level of p27(Kip1) expression is evident from the very early stages of hepatocarcinogenesis. METHODS: In the present study, expression of p27(Kip1) and Jun activation domain binding protein-1 (Jab1), which is a key molecule involved in posttranslational regulation of p27(Kip1), was evaluated in surgically resected specimens of 8 dysplastic nodules (DNs), 16 early HCCs, and 126 classical HCCs. RESULTS: Immunohistochemistry revealed no Jab1 expression in the majority of hepatocytes in noncancerous normal liver tissue and cases of chronic hepatitis or cirrhosis. In contrast, Jab1 was overexpressed in 50% (4/8) and 50% (8/16) of DNs and early HCCs, respectively, and the labeling index was increased in line with the degree of loss of differentiation in classical HCCs. Real-time quantitative reverse transcription polymerase chain reactions revealed the Jab1 mRNA levels in all tested early and well-differentiated HCCs to be increased compared with matched nontumorous liver specimens. The Spearman coefficient pointed to a high correlation between p27(Kip1) and Jab1 mRNA expression levels (P = 0.0014). CONCLUSIONS: Jab1 expression, as well as p27(Kip1) upregulation, is evident from the very early stages of hepatocarcinogenesis, suggesting that Jab1 could be a diagnostic marker and a treatment target for precancerous lesions and early HCCs. PMID- 20589435 TI - What is the major prognostic factor in tumor-node-metastasis staging of pancreatic adenocarcinoma? PMID- 20589434 TI - Serum midkine correlates with tumor progression and imatinib response in gastrointestinal stromal tumors. AB - BACKGROUND: A previous study identified midkine (MK) expression in primary gastrointestinal stromal tumor (GIST) as a prognostic marker. The aim of the current study was to compare serum midkine (S-MK) concentrations of GIST patients with those of healthy controls and to determine if MK can serve as a prognostic serum marker for these patients. MATERIALS AND METHODS: S-MK concentrations were measured by enzyme-linked immunosorbent assay in GIST patients (n = 96) and healthy controls (n = 148). S-MK levels were then correlated with clinicopathological data and the administration of imatinib therapy. In addition, MK expression was evaluated in 39 surgically resected GIST and in 17 leiomyoma specimens on a tissue microarray. RESULTS: S-MK concentrations in GIST patients were significantly higher than in healthy controls: median (25th and 75th percentiles) S-MK concentration was 235 (139 and 376) pg/ml in the GIST patients and 99 (33 and 198) pg/ml in the controls (P < 0.001; Mann-Whitney U test). Significantly higher median S-MK concentrations were found in GIST with recurrence compared with those without (295 vs 230; P = 0.009). GIST patients with S-MK levels higher than 400 pg/ml showed a significantly worse recurrence free survival (P = 0.026; log-rank test). Patients receiving imatinib therapy had decreased median S-MK concentrations compared with those who were not treated with imatinib (331 vs 201; P < 0.001). CONCLUSIONS: S-MK concentration is a potential marker for evaluating the progression and prognosis of GIST, especially during imatinib therapy. Further studies could focus on the role of midkine in the tumorigenesis of GIST and responsiveness toward imatinib therapy. PMID- 20589436 TI - Robotic-assisted versus laparoscopic surgery for low rectal cancer: case-matched analysis of short-term outcomes. AB - PURPOSE: The aim of this study is to compare short-term outcomes and surgical quality of robot-assisted (RAP) and laparoscopic (LAP) total mesorectal excision (TME) in patients with low rectal cancer. METHODS: From December 2007 to June 2009, 41 consecutive patients with low rectal cancer underwent TME by robot assisted procedures. The lowest tumor margins were below peritoneal reflection and 1.0-8.0 cm above the anal verge. These patients were matched 1:2 by age, gender, body mass index, date of surgery, American Society of Anesthesiologists score, and tumor stage, with 82 patients who underwent conventional LAP. Macroscopic quality of the specimens and operative and postoperative outcomes were compared. RESULTS: Mean operation time was 168.0 +/- 49.3 min for LAP group and 231.9 +/- 61.4 min for RAP group (P < 0.001). Time to regular diet (RAP, 6.7 days vs. LAP, 6.6 days) and length of stay (RAP, 9.9 days vs. LAP, 9.4 days) were similar. The proportion of surgeries performed with the modified natural orifice techniques (totally intracorporeal procedures with transanal or transvaginal retrieval of specimens) was significantly higher in the RAP group (RAP, 48.8% vs. LAP, 13.4%; P < 0.001). There were no between-group differences in specimen quality, including distal resection margins, harvested lymph nodes, and circumferential margins. The overall major complication rates were similar (RAP, 9.8% vs. LAP, 7.3%; P = 0.641). CONCLUSIONS: RAP was safe and effective for patients with low rectal cancer. Furthermore, the technical advantages of robot surgical systems may allow a novel approach using hybrid natural orifice surgery. PMID- 20589437 TI - Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration. AB - Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a 'screen') to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In 'preliminary studies', a maximum tolerated dose (MTD) for each drug was determined for use in 'main studies'. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man. PMID- 20589438 TI - Improving medication adherence by using practitioner nonverbal techniques: a field experiment on the effect of touch. AB - Though the positive effect of touch on compliance has been widely reported in the social psychology literature, a new evaluation has been made in a health setting. Six general practitioners were instructed to touch (or not) their patients on the forearm for 1-2 s. Patients who suffered from mild pharyngitis were solicited by the practitioners at the end of the consultation for a verbal promise to take the antibiotic medication as prescribed. One week later, patients were contacted at home to determine the number of pills that had been taken and to evaluate the practitioner. Touch increased medication adherence in both male and female patients, but was associated with a greater increase in male patients. It was also found that practitioners were perceived to be more concerned about their patients by those in the touch condition. Practitioner competence appeared to be slightly higher in the touch condition. The theoretical implications of this positive effect of tactile contact are discussed and the practical interest for practitioners is highlighted, showing how this nonverbal technique could help them to increase the medication adherence of their patients. PMID- 20589439 TI - Comprehension of complex instructions deteriorates with age and vascular morbidity. AB - Verbal comprehension is critical to the success of medical counseling. Here, we tested how age and vascular risk factors affect the ability to understand complex instructions. Verbal comprehension, cognitive functions, and vascular risk factors were assessed in 39 mid- and 38 late-life community-dwelling individuals (48 to 59 years and >59 years of age, respectively). To test for verbal comprehension, we used a modified version of the Token Test (TT). In midlife individuals, education (beta = 0.572, p < 0.05) was the only predictor for extended-TT performance. In late-life individuals, age (beta = -1.015, p < 0.001) and body mass index (beta = -0.651, p = 0.003) were significantly correlated with extended-TT performance and explained 50% of the variance in extended-TT performance (adjusted R (2) = 0.503). This relation is only partly explained by conventional neuropsychological measures as the ones used in our test battery. These results indicate that aging and overweight impair comprehension of complex instructions. Therefore, medical counseling appropriate for midlife individuals may be less successful in elderly people and particularly in those with metabolic disturbances. PMID- 20589440 TI - Influence of organic waste and residue mud additions on chemical, physical and microbial properties of bauxite residue sand. AB - BACKGROUND, AIM AND SCOPE: In an alumina refinery, bauxite ore is treated with sodium hydroxide at high temperatures and pressures and for every tone of alumina produced, about 2 tones of alkaline, saline bauxite processing waste is also produced. At Alcoa, a dry stacking system of disposal is used, and it is the sand fraction of the processing waste that is rehabilitated. There is little information available regarding the most appropriate amendments to add to the processing sand to aid in revegetation. The purpose of this study was to investigate how the addition of organic wastes (biosolids and poultry manure), in the presence or absence of added residue mud, would affect the properties of the residue sand and its suitability for revegetation. MATERIALS AND METHODS: Samples of freshly deposited residue sand were collected from Alcoa's Kwinana refinery. Samples were treated with phosphogypsum (2% v/v), incubated, and leached. A laboratory experiment was then set up in which the two organic wastes were applied at 0 or the equivalent to 60 tones ha(-1) in combination with residue mud added at rates of 0%, 10% and 20% v/v. Samples were incubated for 8 weeks, after which, key chemical, physical and microbial properties of the residue sand were measured along with seed germination. RESULTS AND DISCUSSION: Additions of residue mud increased exchangeable Na(+), ESP and the pH, and HCO (3) (-) and Na(+) concentrations in saturation paste extracts. Additions of biosolids and poultry manure increased concentrations of extractable P, NH (4) (+) , K, Mg, Cu, Zn, Mn and Fe. Addition of residue mud, in combination with organic wastes, caused a marked decrease in macroporosity and a concomitant increase in mesoporosity, available water holding capacity and the quantity of water held at field capacity. With increasing residue mud additions, the percentage of sample present as sand particles (<1 mm diameter) decreased, and the percentage present in aggregated form (>2 mm diameter) increased; greatest aggregation occurred where a combination of residue mud and poultry manure were added. Stability of aggregates, as measured by wet sieving, was greatest where poultry manure was applied. Although total organic C and soluble organic C were greater in biosolids than poultry manure treatments, the reverse was the case for microbial biomass C and basal respiration. In the biosolids and poultry manure treatments, increasing residue mud additions tended to increase soluble C, microbial biomass C and basal respiration. Germination index of watercress was highest in control samples and reduced by additions of biosolids and poultry manure which was attributed to the high EC and possibly high extractable P and NH (4) (+) . CONCLUSIONS: The concurrent addition of residue mud and organic wastes can improve chemical, microbial and particularly physical properties of residue sand. Future research should include neutralisation of the mud (e.g. with gypsum) and subsequent leaching to remove salts originating from both the mud and organic wastes. PMID- 20589441 TI - Accelerating simultaneous algebraic reconstruction technique with motion compensation using CUDA-enabled GPU. AB - PURPOSE: To accelerate the simultaneous algebraic reconstruction technique (SART) with motion compensation for speedy and quality computed tomography reconstruction by exploiting CUDA-enabled GPU. METHODS: Two core techniques are proposed to fit SART into the CUDA architecture: (1) a ray-driven projection along with hardware trilinear interpolation, and (2) a voxel-driven back projection that can avoid redundant computation by combining CUDA shared memory. We utilize the independence of each ray and voxel on both techniques to design CUDA kernel to represent a ray in the projection and a voxel in the back projection respectively. Thus, significant parallelization and performance boost can be achieved. For motion compensation, we rectify each ray's direction during the projection and back-projection stages based on a known motion vector field. RESULTS: Extensive experiments demonstrate the proposed techniques can provide faster reconstruction without compromising image quality. The process rate is nearly 100 projections s (-1), and it is about 150 times faster than a CPU-based SART. The reconstructed image is compared against ground truth visually and quantitatively by peak signal-to-noise ratio (PSNR) and line profiles. We further evaluate the reconstruction quality using quantitative metrics such as signal-to noise ratio (SNR) and mean-square-error (MSE). All these reveal that satisfactory results are achieved. The effects of major parameters such as ray sampling interval and relaxation parameter are also investigated by a series of experiments. A simulated dataset is used for testing the effectiveness of our motion compensation technique. The results demonstrate our reconstructed volume can eliminate undesirable artifacts like blurring. CONCLUSION: Our proposed method has potential to realize instantaneous presentation of 3D CT volume to physicians once the projection data are acquired. PMID- 20589442 TI - Diagnostic role of colour Doppler US at 1-year follow-up after orthotopic liver transplantation. AB - PURPOSE: This paper discusses the role of colour Doppler ultrasound (CDUS) in the midterm follow-up of patients after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: We retrospectively studied 134 patients--102 men and 32 women, age range 21-68 years--who underwent liver transplantation between May 2006 and April 2007. In the first week after OLT, CDUS examination was performed daily in patients with anastomoses at a high risk of thrombosis, and on the basis of clinical and laboratory findings in other patients. After discharge, follow-up was performed 1, 3, 6 and 12 months after transplantation. Any new parenchymal focal lesion was studied by computed tomography (CT) and, where needed, biopsy. RESULTS: CDUS identified the following complications: 22 biliary (B), nine vascular (V) and seven focal lesions (FL). Sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were, respectively: 79.2%, 97.3%, 86.3%, 95.5%, 94% (B), 100%, 99.2%, 88.9%, 100%, 99.3% (V) and 100%, 96.9%, 42.8%, 100%, 97% (FL). CDUS also showed 16 blood collections and eight suspected biliary collections (four of which were confirmed by percutaneous puncture). CONCLUSIONS: CDUS is an essential diagnostic tool in the follow-up of OLT. An early diagnosis of complications can improve graft integrity and patient survival. PMID- 20589443 TI - The long-term results of distal gastrectomy by mini-laparotomy in early gastric cancer patients. AB - INTRODUCTION: Radical distal gastrectomy by mini-laparotomy is an alternative surgical treatment modality with technical feasibility in early gastric cancer (EGC) patients. The aim of this study is to assess the oncologic feasibility of distal gastrectomy by mini-laparotomy in EGC patients through a long-term survival analysis based on the prospectively collected data. PATIENTS AND METHODS: From January 2003 to November 2003, a total of 53 EGC patients who received distal gastrectomy by laparotomy were enrolled in this study. These patients were divided into two groups, that is, the mini-laparotomy group (ML, n = 22) and the conventional laparotomy group (CL, n = 31). A comparative long-term survival analysis was performed. RESULTS: The hospital stay was significantly shorter in mini-laparotomy group (P = 0.002). However, there were no significant differences in the pathologic results such as the resection margin and the number of harvested lymph nodes. In long-term survival results, there were no significant differences in disease-free and overall survival rate of the patients according to the method of laparotomy. CONCLUSIONS: Radical distal gastrectomy by mini-laparotomy in EGC patients would be also one of the minimally invasive surgical modality in oncologic aspect. PMID- 20589444 TI - The need of a severity scoring system for postoperative pancreatic fistulas. PMID- 20589446 TI - Laparoscopic distal pancreatectomy offers shorter hospital stays with fewer complications. AB - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is increasingly performed for lesions of the body and tail of the pancreas. The aim of this study was to investigate short-term outcomes after LDP compared to open distal pancreatectomy (ODP) at a single, high-volume institution. METHODS: We reviewed records of patients who underwent distal pancreatectomy (DP) and compared perioperative data between LDP and ODP. Continuous variables were compared using Student's t or Wilcoxon rank-sum tests. Categorical variables were compared using chi-square or Fisher's exact test. RESULTS: A total of 360 patients underwent DP. Beginning in 2001, 95 were attempted, and 71 were completed laparoscopically with a 25.3% conversion rate. Compared to ODP, LDP had similar rates of splenic preservation, pancreatic fistula, and mortality. LDP had lower blood loss (150 vs. 900 mL, p < 0.01), smaller tumor size (2.5 vs. 3.6 cm, p < 0.01), and shorter length of resected pancreas (7.7 vs. 10.0 cm, p < 0.01). LDP had fewer complications (28.2% vs. 43.8%, p = 0.02) as well as shorter hospital stays (5 vs. 6 days, p < 0.01). CONCLUSIONS: LDP can be performed safely and effectively in patients with benign or low-grade malignant neoplasms of the distal pancreas. When feasible in selected patients, LDP offers fewer complications and shorter hospital stays. PMID- 20589447 TI - Factors predicting failure following high bilio-enteric anastomosis for post cholecystectomy benign biliary strictures. AB - INTRODUCTION: Failures following Roux-en-Y hepatico-jejunostomy (HJ) for post cholecystectomy benign bile duct strictures (BBS) pose significant challenge. This study was aimed to find out the factors predicting failure after surgical repair in patients with BBS. METHODS: Between January 1989 and May 2007, 364 patients underwent Roux-en-Y HJ to the hilum for BBS. With a median follow-up of 61 (6-212) months, 334 (92%) patients had successful outcome and 30 (8%) had failure. A multivariate analysis was performed to find out the factors predicting failure. RESULTS: Thirty patients who had failure became symptomatic after a median of 35 months (3 days-190 months) after surgical repair. Out of 30 patients, 11 (37%) were experiencing occasional episodes of cholangitis responding to antibiotics. All have patent anastomosis on nuclear scintigraphy and/or cholangiography. Cholangiogram demonstrated anastomotic stricture in 19/30 (63%) patients. Eighteen patients underwent re-intervention for re-strictures (nine--percutaneous balloon dilatation of the stricture, five--revision HJ, one- right hepatectomy, three--a combination of interventions). One patient refused to undergo a planned percutaneous balloon dilatation. Out of 18 patients, 12 (67%) had successful outcome following re-interventions. One patient who underwent revision HJ after a failed percutaneous balloon dilatation died in the immediate postoperative period. Preoperative bilirubin (p = 0.001), attempted bilio-enteric anastomosis before referral (0.004), cirrhosis (0.006), portal hypertension (p = 0.056), repair in the presence of external biliary fistula (0.000), and spontaneous bilio-enteric fistula (p = 0.011) were the factors found to be predicting failure of surgical repair on multivariate analysis. CONCLUSIONS: Previous attempts of repair and delay in repair which predispose cirrhosis and portal hypertension may cause failure of surgical management in patients with BBS. In patients presenting with external biliary fistula, for a better outcome, surgical repair may be delayed till the fistula resolves. PMID- 20589449 TI - Cloning and characterization of a sucrose isomerase from Erwinia rhapontici NX-5 for isomaltulose hyperproduction. AB - The sucrose isomerase (SIase) gene from an efficient strain of Erwinia rhapontici NX-5 for isomaltulose hyperproduction was cloned and overexpressed in Escherichia coli. Protein sequence alignment revealed that SIase was a member of the glycoside hydrolase 13 family. The molecular mass of the purified recombinant protein was estimated at 66 kDa by SDS-PAGE. The SIase had an optimal pH and temperature of 5.0 and 30 degrees C, respectively, with a K (m) of 257 mmol/l and V (max) of 48.09 MUmol/l/s for sucrose. To the best of our knowledge, the recombinant SIase has the most acidic optimum pH for isomaltulose synthesis. When the recombinant E. coli (pET22b- palI) cells were used for isomaltulose synthesis, almost complete conversion of sucrose (550 g/l solution) to isomaltulose was achieved in 1.5 h with high isomaltulose yields (87%). The immobilized E. coli cells remained stable for more than 30 days in a "batch"-type enzyme reactor. This indicated that the recombinant SIase could continuously and efficiently produce isomaltulose. PMID- 20589448 TI - Mortality in perforated duodenal ulcer depends upon pre-operative risk: a retrospective 10-year study. AB - INTRODUCTION: Most patients presenting with acutely perforated duodenal ulcer undergo operation, but conservative treatment may be indicated when an ulcer has spontaneously sealed with minimal/localised peritoneal irritation or when the patient's premorbid performance status is poor. We retrospectively reviewed our experience with operative and conservative management of perforated duodenal ulcers over a 10-year period and analysed outcome according to American Society of Anesthesiologists (ASA) score. METHODS: The records of all patients presenting with perforated duodenal ulcer to the Department of Surgery, Mayo General Hospital, between January 1998 and December 2007 were reviewed. Age, gender, co morbidity, ASA-score, clinical presentation, mode of management, operative procedures, morbidity and mortality were considered. RESULTS: Of 76 patients included, 48 (44 operative, 4 conservative) were ASA I-III, with no mortality irrespective of treatment. Amongst 28 patients with ASA-score IV/V, mortality was 54.5% (6/11) following operative management and 52.9% (9/17) with conservative management. CONCLUSION: In patients with a perforated duodenal ulcer and ASA score I-III, postoperative outcome is uniformly favourable. We recommend these patients have repair with peritoneal lavage performed, routinely followed postoperatively by empirical triple therapy. Given that mortality is equivalent between ASA IV/V patients whether managed operatively or conservatively, we suggest that both management options are equally justifiable. PMID- 20589450 TI - Rupture of cerebral myxomatous aneurysm months after resection of the primary cardiac tumor. AB - BACKGROUND: The natural history of cerebral aneurysms derived from metastatic spread of cardiac myxomas is not well known, and their management presents many dilemmas. METHODS: Case report and literature review. RESULTS: An 18-year-old man presented with an intraparenchymal hemorrhage several months after resection of an atrial myxoma. Angiography showed several myxomatous aneurysms, one of which had bled. The patient had a recurrent hemorrhage before undergoing surgical resection. MRI, angiographic, and pathological data are presented for this rare condition. CONCLUSIONS: Myxomatous aneurysms are important entities for neurointensivists to recognize and can present years after diagnosis. Patients presenting with cerebral infarction or hemorrhage of unknown etiology should undergo cardiac imaging to rule out atrial myxoma, as up to 50% of patients with myxomas present initially with stroke. PMID- 20589451 TI - Levodopa-responsive parkinsonism after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Levodopa-responsive Parkinsonism is a rare complication of subarachnoid hemorrhage and no cases have been reported to occur in the absence of hydrocephalus. METHODS: Case report. RESULTS: We describe a 42-year-old woman who developed progressive severe Parkinsonism in the second week after aneurysmal subarachnoid hemorrhage. No hydrocephalus was present. Neuroimaging revealed striking abnormalities of the midbrain in the region of the substantia nigra. She was ultimately treated with high dose levodopa/carbidopa with a dramatic response. CONCLUSIONS: This case suggests that Parkinsonism may occur as a delayed complication of subarachnoid hemorrhage, and that in these patients, a trial of levodopa-carbidopa may be warranted. PMID- 20589452 TI - Abdominal aortic dissection with atypical presentation. PMID- 20589453 TI - Giant area of transient hepatic attenuation difference, mimicking incidentaloma at liver ultrasound. PMID- 20589455 TI - Overexpression of mouse estrogen receptor-beta decreases but its transactivation and ligand binding domains increase the growth characteristics of E. coli. AB - Escherichia coli is one of the most common and widely used prokaryotic hosts for the expression of recombinant proteins. The overexpression of recombinant proteins occasionally increases bacterial growth but sometimes reduces it and becomes lethal to the host cells. Here, we report the overexpression of mouse ER beta and its domains in the prokaryotic expression system and its opposite effect on the growth characteristics of E. coli. ER-beta protein was immunologically detected as a 53 kDa his-tag protein in the pellet of the bacterial lysate. Its overexpression, as reflected by the total protein content and expression pattern, resulted in the decrease of bacterial growth. However, the overexpression of ER beta transactivation domain (TAD) using pIVEX and ligand binding domain (LBD) using pRSETA in E. coli BL21 (DE3) show opposite pattern. TAD was immunologically detected as 20 kDa and LBD as 22 kDa protein in the supernatant of the bacterial lysate and their overexpression increased the bacterial growth. PMID- 20589454 TI - Defining structural domains of an intrinsically disordered protein: Sic1, the cyclin-dependent kinase inhibitor of Saccharomyces cerevisiae. AB - The cyclin-dependent kinase inhibitor Sic1 is an intrinsically disordered protein (IDP) involved in cell-cycle regulation in the yeast Saccharomyces cerevisiae. Notwithstanding many studies on its biological function, structural characterization has been attempted only recently, fostering the development of production and purification protocols suitable to yield large amounts of this weakly expressed protein. In this study, we describe the identification of protein domains by the heterologous expression, purification, and characterization of Sic1-derived fragment. Four C-terminal fragments (Sic1(C ter)) were produced based on functional studies and limited-proteolysis results. The N-terminal fragment (Sic1(1-186)) was complementary to the most stable C terminal fragments (Sic1(Delta186)). Both Sic1(1-186) and Sic1(C-ter) fragments were, in general, less susceptible to spontaneous proteolysis than the full length protein. The boundaries of the C-terminal fragments turned out to be crucial for integrity of the recombinant proteins and required two rounds of design and production. Sic1 fragments were purified by a simple procedure, based on their resistance to heat treatment, at the amount and purity required for structural characterization. Circular dichroism (CD) measurements and nuclear magnetic resonance (NMR) spectra of N- and C-terminal fragments confirm their disordered nature but reveal minor structural differences that may reflect their distinct functional roles. PMID- 20589456 TI - Heparin promotes suspension adaptation process of CHO-TS28 cells by eliminating cell aggregation. AB - While heparin has been shown to eliminate cell aggregation in suspension adaptations of insect and HEK293 cells for virus-based cell cultures, the role of heparin in long period serum-free suspension adaptation of the anchorage dependent Chinese hamster ovary (CHO) cell lines remains inconclusive. In this paper, we explore the potential application of heparin in suspension adaptation of CHO cell line which produces an anti-human chimeric antibody cHAb18. Heparin showed a concentration-dependent inhibition of CHO-TS28 cell-to-cell adhesion, with a significant inhibitory effect occurring when the concentration exceeded 250 MUg/ml (P < 0.001). Heparin also exhibited a cell aggregation elimination role at all concentrations (P < 0.001). Furthermore, heparin promoted cell growth and antibody secretion, with the highest cell density ((99.83 +/- 12.21) * 10(4) cells/ml, P = 0.034) and maximum antibody yield ((9.46 +/- 0.94) mg/l, P < 0.001) both occurring at 250 MUg/ml heparin. When agitated, cell aggregates were effectively dispersed by 250 MUg/ml heparin and a single-cell suspension culture process was promoted. In suspension adapted CHO-TS28 cells, cell growth rates and specific antibody productivity were maintained; while antigen-binding activity improved slightly. Together, our results show that heparin may promote suspension adaptation of anchorage-depended CHO cells by resisting cell aggregation without reducing cell growth, antibody secretion, and antigen-binding activity. PMID- 20589457 TI - Staphylococcal sepsis presenting as pulmonary embolism. AB - Deep vein thrombosis in children is rare and is often secondary to a predisposing condition. Staphylococcal sepsis following furunculosis and complicated by deep vein thrombosis and septic pulmonary emboli in a fourteen-yr-old boy is presented. He was managed successfully with antibiotics and anticoagulation. PMID- 20589458 TI - Hepicidin and its role in iron metabolism. PMID- 20589459 TI - Complications among premature neonates treated with beractant and poractant alfa. AB - OBJECTIVE: To compare the complications among preterm infants treated with two different natural surfactants. METHODS: In a randomized clinical trial, 150 preterm infants with Respiratory distress syndrome (RDS) treated with exogenous surfactant, were enrolled in the study. Group A consisted of 79 neonates that received poractant (curosurf). Seventy one newborn infants in group B were treated with beractant (Survanta). RESULTS: The mean gestational age for group A and B were 29.40+/-2.90 wk and 29.50+/-2.73 wk (P=0.82), respectively. The demographic and clinical variables were similar in both groups. The mean duration of intubation (as a primary outcome) was significantly shorter in infants treated with poractant (3.13+/-1.80 vs 4.06+/-2.7 days p=0.05). The mean duration of need for oxygen and hospitalization of patients in group A and B were 17.73+/-22.25 vs 19.14+/-17.85 days (p=0.67) and 24.89+/-26.41 vs 29.14+/-23.54 days (p= 0.32), respectively. There was no significant difference between groups with respect to mortality and morbidity, including pulmonary hemorrhage, intraventricular hemorrhage (IVH), patent ductus arteriosus, sepsis, and bronchopulmonary dysplasia (secondary outcome). CONCLUSIONS: In this study, infants who received poractant had shorter duration of intubation than infants treated with beractant, without any difference in the duration of oxygen therapy or hospitalization. There was no significant superiority of poractant over beractant. PMID- 20589460 TI - Megaloblastic anemia: back in focus. AB - Megaloblastic anemia (MA), in most instances in developing countries, results from deficiency of vitamin B(12) or folic acid. Over the last two to three decades, incidence of MA seems to be increasing. Of the two micronutrients, folic acid deficiency contributed to MA in a large majority of cases. Now deficiency of B(12) is far more common. In addition to anemia, occurrence of neutropenia and/or thrombocytopenia is increasingly being reported. Among cases presenting with pancytopenia, MA stands out as an important (commonest cause in some series) cause. This article focuses on these and certain other aspects of MA. Possible causes of increasing incidence of MA are discussed. Observations on other clinical features like neurocognitive dysfunction, associated hyperhomocysteinemeia and occurrence of tremors and thrombocytosis during treatment are highlighted. PMID- 20589461 TI - Iron deficiency and infection. AB - Iron deficiency is the most common micronutrient deficiency in the world. Children, particularly infants living in developing countries are highly vulnerable to infectious diseases. Therefore, understanding the relationship between iron deficiency and infection is of great importance. Iron deficiency is associated with impairment of innate (natural) immunity and cell mediated immunity, thereby contributing to increased risk of infections. The iron acquisition by the microbes and their virulence is determined by various host and microbial mechanisms. Altering these mechanisms might provide modes of future therapy for infectious diseases. PMID- 20589462 TI - Overt testicular disease at diagnosis in childhood acute lymphoblastic leukemia: prognostic significance and role of testicular irradiation. AB - OBJECTIVE: To analyze the prognostic impact of overt testicular disease (OTD) at diagnosis and role of testicular irradiation in the same. METHODS: Data of 579 boys treated at our center over 16 years was reviewed. RESULTS: Fourteen (2.4%) males had OTD. 10 (71.4%) of these had high-risk disease. Patients with OTD, had a significantly higher incidence of mediastinal-adenopathy (p=0.001), hyperleucocytosis (p=0.004) and CNS disease at presentation (p<0.0001) compared to patients in continuous complete remission (CCR). 4 of the 11 patients with OTD, who opted for therapy, had relapse; 2 are in CCR. Although, survival in patients with OTD was inferior (p=0.183) compared to patients without OTD, it was not an independent prognostic factor (p=0.47). In the entire study cohort, symptom-diagnosis interval (p=0.006), white cell (p=0.001) and platelet count (p=0.001) at presentation were significantly associated with survival (Cox multivariate regression analysis). CONCLUSIONS: OTD was not an independent prognostic factor, despite association with high-risk features. Survival outcome was inferior. The observations indicate the need of revaluation of the present protocol with incorporation of intermediate dose and subsequently high-dose methotrexate (after assessment for toxicity and tolerance), risk-stratified therapy and plausibly omission of testicular irradiation. PMID- 20589463 TI - Asymptomatic colonization of upper respiratory tract by potential bacterial pathogens. AB - OBJECTIVE: To screen for asymptomatic respiratory carriage of S. pneumoniae, H. influenzae and Group A Streptococcus (GAS) in children attending JIPMER, correlate carriage rate with different socio-demographic factors and to detect antimicrobial resistance among the isolates. METHODS: Throat swabs were collected from both in patients and out patients (1 organism. Antibiotic resistance was highest in S. pneumoniae with 66.7% of strains resistant to penicillin. MDR strains were also encountered. Erythromycin resistance was observed in both H. influenzae (28.4%) and GAS (22%). No statistically significant association was found between the carriage rate of these organisms and different socio-demographic factors. CONCLUSIONS: S. pneumoniae carriage rate was comparatively higher in the Community and its antimicrobial resistance is an issue to address. PMID- 20589464 TI - Complement components (C3, C4) as inflammatory markers in asthma. AB - OBJECTIVE: To assess the serum levels of complement factors C3 and C4 in Egyptian asthmatic children. METHODS: This case-controlled study comprised of 60 Egyptian children with the diagnosis of bronchial asthma (not in acute attack) and 60 age and sex-matched healthy controls. All candidates were subjected to a thorough clinical study, complete blood counts, absolute eosinophil count and serum complements (C3, C4). RESULTS: Serum C3 was significantly higher in asthmatics when compared to controls (140.60 +/- 38.80 mg/dl vs 107.70 +/- 45.00 mg/dl respectively, (p = 0.01). However, differences in serum C4 levels were not significant (41.30+/-48.80 mg/dl vs 44.60 +/- 39.70 mg/dl respectively, p = 0.69). There was a significant positive correlation between severity of asthma and serum C3 (p=0.02) but not with serum C4. CONCLUSIONS: Serum levels of C3 - but not C4 - are elevated in children with stable asthma, with a positive correlation between serum C3 and severity of asthma. PMID- 20589465 TI - Impact of NGO run mid day meal program on nutrition status and growth of primary school children. AB - OBJECTIVE: To study the impact of wholesome mid day meal (MDM) program run by an NGO on the growth of the primary school students in rural area of Mathura district. METHODS: This intervention study involved children enrolled in Government run rural primary schools in Mathura district in Uttar Pradesh from March 06 through August 07. A wholesome, nutritionally balanced MDM provided by an NGO for the students in the 6 primary schools was selected as intervention group. Control group consisted of children in 8 schools which received locally prepared MDM by village panchayats. Height, weight, change in height/month, change in weight/month, prevalence of protein-energy malnutrition and prevalence of signs of vitamin deficiencies, were measured. RESULTS: Food was provided for 221 days in one year. Within group and between groups repetitive measures were compared using generalized estimating equation (GEE). Within both intervention and control groups height and weight had significantly increased (p < 0.05), while there was no significant difference between the groups. There was no change in prevalence of malnutrition within either of the groups. Reduction in vitamin A deficiency signs was 38% more in intervention group (p < 0.001). Prevalence of Vitamin D deficiency reduced by 50% more in intervention group. No such differences between groups were observed for vitamin B complex and vitamin C. CONCLUSIONS: MDM provided by the NGO has no better impact on growth of the primary school children, however, it reduced prevalence of vitamin deficiency significantly in comparison to the MDM run by Village Panchayats. PMID- 20589466 TI - Human touch to detect hypothermia in neonates in Indian slum dwellings. AB - OBJECTIVE: To assess the validity of human touch (HT) method to measure hypothermia compared against axillary digital thermometry (ADT) and study association of hypothermia with poor suckle and underweight status in newborns and environmental temperature in 11 slums of Indore city, India. METHODS: Field supervisors of slum-based health volunteers measured body temperature of 152 newborns by HT and ADT, observed suckling and weighed newborns. Underweight status was determined using WHO growth standards. RESULTS: Hypothermia prevalence (axillary temperature <36.5 degrees C) was 30.9%. Prevalence varied by season but insignificantly. Hypothermia was insignificantly associated with poor suckle (31% vs 19.7%, p=0.21) and undernutrition (33.3% vs 25.3%, p=0.4). HT had moderate diagnostic accuracy when compared with ADT (kappa: 0.38, sensitivity: 74.5%, specificity: 68.5%). CONCLUSIONS: HT emerged simpler and programmatically feasible. There is a need to examine whether trained and supervised community based health workers and mothers can use HT accurately to identify and manage hypothermia and other simple signs of newborn illness using minimal algorithm at home and more confidently refer such newborns to proximal facilities linked to the program to ensure prompt management of illness. PMID- 20589467 TI - Sonographic diagnosis of Ascaris lumbricoides infestation as a cause of intestinal obstruction. PMID- 20589468 TI - Health related quality of life among children with cancer in Hyderabad, India. PMID- 20589469 TI - Can Indian classical instrumental music reduce pain felt during venepuncture? PMID- 20589470 TI - Can Indian classical instrumental music reduce pain felt during venepuncture? PMID- 20589471 TI - Antenatal diagnosis of Larsen syndrome. PMID- 20589472 TI - Neonatal research: parent's perception of informed consent. PMID- 20589473 TI - Respiratory syncitial virus in children with acute respiratory infections. AB - OBJECTIVE: To study the nutritional status of children with Respiratory Syncitial virus infection. METHODS: One hundred and twenty six children with acute respiratory infection, between the age of 4-24 months, were investigated for RSV infection with bronchiolitis, pneumonia and upper respiratory tract infection. Nasopharyngeal aspirates were collected and cytokine responses were determined by ELISA. Upper respiratory tract infections were detected in 16.66%, bronchiolitis in 30.15% and Pneumonia in 53.17% children. RESULTS: Of the 126 patients, 46.66% children were positive for RSV while 58.33% were negative for RSV. Children with bronchiolitis were more commonly positive for RSV compared to URTI and pneumonia. RSV was almost equally distributed among boys (42.5%) and girls (48.7%). More children were RSV positive when the mean age lesser (8.4 mo) was compared to RSV negative (9.93 mo). Well nourished children and children with normal birth weight had more RSV positives, though not statistically significant. In a sub sample analysis of cytokines done (n=25), Interleukin-2 and Interleukin-8 levels were higher in the RSV positive children and these levels declined after 5 days of illness. CONCLUSIONS: RSV is more commonly associated with bronchiolitis in younger infants with normal birth weight or more weight for age (WFA). Proinflammatory cytokine IL-8 was secreted at high concentrations in the nasopharyngeal aspirate in all the children. PMID- 20589474 TI - Moyamoya disease. PMID- 20589475 TI - Penile epidermal inclusion cyst. AB - We report a case of epidermal inclusion cyst of penis in a five-year-old boy, who had presented to the outpatient department of our hospital. Epidermal inclusion cysts are benign lesions that can develop in any part of the body. However, the finding of an epidermal inclusion cyst in the penis is rare. The child was operated and discharged uneventfully. The objective of reporting this case is to highlight the rare possibility of an inclusion cyst arising from penis as a late complication of circumcision. PMID- 20589476 TI - Infracardiac total anomalous pulmonary venous drainage with unusual presentation. AB - Total anomalous pulmonary venous drainage (TAPVD) is a rare entity which forms approximately 0.4 to 2% of all congenital heart disease. The infracardiac type usually involve obstructions on pulmonary venous connections and comprising a quarter of all TAPVD cases. The clinical findings in patients with obstructed infracardiac TAPVD could mimic respiratuary distress of several different etiologies during first hours of life. In this article, we present a case of a neonate with infracardiac type of TAPVD presented with only distinct subcutaneous veins of abdominal and thoracic wall. PMID- 20589477 TI - Congenital Langerhans cell histiocytosis with skin and lung involvement: spontaneous regression. AB - Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare type of Langerhans Cell Histiocytosis, presenting at birth or during the neonatal period with eruption of multiple, discrete red-brown papules or nodules that undergo spontaneous regression. Systemic signs are generally absent. We describe a 4 month-old infant presenting with reddish brown nodular cutaneous lesions since birth with a past history suggestive of pulmonary involvement. Skin biopsy showed a dermal infiltrate of pleomorphic histiocytes; which were CD1a and S-100 positive, consistent with the diagnosis of CSHLCH. Both pulmonary and cutaneous lesions showed spontaneous resolution. PMID- 20589478 TI - An unusual presentation of thoracic para-aortic hematoma due to blunt trauma. AB - An 11-yr-old boy was admitted to the hospital with gradually aggravating acute abdominal pain along with nausea, vomiting and constipation for 5 days. The pain started after blunt trauma on the superior abdomen. He had normal laboratory tests and abdominal examination, but his chest radiograph showed infiltration in the right lung and an abnormal mass on the left diaphragm. Further investigation like computed tomography (CT) and magnetic resonance MR angiography, revealed an abnormal para-aortic mass located a mass located para-aortic above posterior to the left diaphragm with a well-defined margin. The abnormal mass was finally confirmed to be a hematoma with exploratory thoracotomy. The rarity of this kind of presentation is discussed for making an early and correct diagnosis. PMID- 20589479 TI - Salmonella enterica enteritidis arthritis following trauma in a child with thalassemia major. AB - Osteoarticular infections caused by Non-typhi Salmonella are exceptionally encountered. We report a case of a bacteriologically documented knee joint infection due to Salmonella enterica serotype enteritidis, following trauma in a child with thalassemia major. Emergency arthrotomy combined with antimicrobial therapy was helpful in eradication of infection. Physicians should be aware of this rare manifestation of Non-typhi Salmonella infections in thalassemic patients. PMID- 20589480 TI - Periorificial and acral dermatitis in a newborn having milk intolerance. AB - A 2-week-old infant born at 36-week gestation developed diarrhea and metabolic acidosis when he was put on formula feeding. He was treated for sepsis and was screened for metabolic diseases. Blood and cerebrospinal fluid cultures were clear. The diarrhea and metabolic acidosis settled but recurred when formula feeding was resumed. He developed a florid erythematous rash involving the palms, feet, perioral and perineal regions. Zinc deficiency was confirmed and zinc replacement resulted in prompt resolution of the skin rash. The patient was put on Pepti-Junior and remained well. This case illustrates that zinc deficiency must be sought and treated in an infant with a typical rash involving the palms, feet and body orifices. PMID- 20589481 TI - Persistent hyperinsulinemic hypoglycemia of infancy due to homozygous KCNJ11 (T294M) mutation. AB - Hyperinsulinemic hypoglycemia is the most common cause of persistent hypoglycemia in infancy. While most of the cases are sporadic more than 100 mutations have been reported in the familial type. The authors report a case of familial hyperinsulinemic hypoglycemia with homozygous T294M mutation of the KCNJ11 gene, which responded to diazoxide therapy. PMID- 20589482 TI - Therapeutic hypothermia after cardiac arrest. AB - Despite the publication of two randomized controlled trials of therapeutic hypothermia after cardiac arrest showing a clear benefit in neurologic outcome and mortality nearly a decade ago, the use of therapeutic hypothermia after successful cardiopulmonary resuscitation remains low. This lag in converting clinical research into practice is likely due in part to a lack of familiarity with a relatively new technology and the need for many providers in the chain of care to understand and feel comfortable with its application, from doctors and nurses in the emergency room, to those in the catheterization laboratory, and ultimately to the staff of the intensive care unit. This review summarizes the physiologic consequences of hypothermia as well as the current literature demonstrating the benefit of hypothermia on select patient populations and the impact of hypothermia on outcome assessment after cardiac arrest. PMID- 20589483 TI - Risk factors, predictors, and markers for work-related asthma and rhinitis. AB - The burden of asthma attributable to occupational exposures is significant. A better evaluation of markers of asthma and rhinitis in occupational settings may help reduce the frequency of occupational asthma (OA) and rhinitis (OR). This publication reviews articles published in 2008 and 2009 to provide an update on aspects related to markers of asthma and rhinitis. Markers derived from occupational exposure assessment, questionnaires, clinical data, and noninvasive tests such as functional tests or measures of serum antibodies are used to develop prediction models for the likelihood of OA and OR development. Findings from prospective studies highlight the course of preclinical signs and markers of airway inflammation in the natural history of OA and OR. Airway inflammation, evaluated by quantification of cells and mediators in induced sputum or nasal lavage and by exhaled nitric oxide, is associated with OA and OR; however, the sensitivity and specificity of these means, especially exhaled nitric oxide, have not been sufficiently assessed. PMID- 20589484 TI - The role of inhalant food allergens in occupational asthma. AB - Workers handling food products and derivatives are at increased risk of developing occupational asthma. Exposure to food allergens occurs primarily through inhalation of dust, steam, vapors, and aerosolized proteins generated during cutting, scrubbing or cleaning, cooking or boiling, and drying activities. Suspicion of the diagnosis of occupational asthma should lead to proper investigation to confirm the diagnosis objectively. Most inhaled food allergy is IgE mediated, and skin prick tests or specific IgE tests are useful tools to support the diagnosis, but objective evidence of asthma by monitoring of peak expiratory flows at and off work or specific inhalation challenges offers a better diagnostic value. This article provides a list of the various foods, food additives, and contaminants that have been associated with occupational asthma. PMID- 20589485 TI - Managing comorbid disease in patients with psoriatic arthritis. AB - Psoriatic arthritis (PsA) is a unique type of inflammatory arthritis that is associated with skin psoriasis. The concept that PsA is simply a skin and joint disease has been challenged by large epidemiologic studies that link PsA with substantial comorbidity. Important comorbidities related to PsA include premature cardiovascular disease, infectious complications, malignancy risk, osteoporosis, and reduced quality of life. This review focuses on the prevalent comorbid diseases in patients with PsA and highlights how the presence of these associated comorbidities can affect the management of these patients. PMID- 20589486 TI - Large cell neuroendocrine carcinoma of the larynx: definition of an entity. AB - Laryngeal atypical carcinoids (AC/moderately-differentiated neuroendocrine carcinoma) are associated with moderately aggressive clinical behavior; however, a subset of tumors classified as AC have much greater aggressive potential. These tumors fulfill the proposed diagnostic criteria for pulmonary large cell neuroendocrine carcinoma, albeit in the larynx. In the current WHO classification, laryngeal large cell neuroendocrine carcinomas (LCNEC) are classified as variants of AC, whereas pulmonary LCNEC are classified as poorly differentiated neuroendocrine carcinomas. Reported outcomes for pulmonary tumors support the separate classification of LCNEC. Five and ten year survival rates for pulmonary AC are 61-73, and 35-59%, respectively, while the 5-year survival rate for pulmonary LCNEC is as low as 30%. By extension, we postulate that the biologic potential of laryngeal LCNEC is similar to that of small-cell carcinoma (poorly-differentiated neuroendocrine carcinoma), and as such, warrants reclassification. The files of Barnes Jewish Hospital/Washington University were searched for the term "neuroendocrine" and the anatomic subsite larynx. Neuroendocrine carcinoma cases were evaluated using the WHO definitions for pulmonary AC and LCNEC; small cell carcinoma was excluded. Cases were also solicited from the larger head and neck pathology community. A literature search was also performed for cases of laryngeal neuroendocrine carcinoma, and cases which could be clearly classified as LCNEC by this scheme were captured as well. Six new cases plus four reported cases were identified which fulfill the WHO criteria for pulmonary LCNEC (eight men and two women). Nine patients presented at stage IV and 88% died of disease (DOD), 75 and 100% of these at 2 and 3 years, respectively. Laryngeal LCNEC is a rare entity, distinct from AC. We recommend that laryngeal tumors fulfilling WHO criteria for pulmonary LCNEC not be classified as variants of AC, but as variants of small cell carcinoma (poorly differentiated neuroendocrine carcinoma) as they are associated with poorer outcome. PMID- 20589487 TI - Diagnosis and prognosis of coronary artery disease: PET is superior to SPECT: Pro. PMID- 20589488 TI - Changes in physical functioning in the Active Living Every Day program of the Active for Life Initiative(r). AB - BACKGROUND: Physical activity can prevent or delay the onset of physical functional limitations in older adults. There are limited data that evidence based physical activity interventions can be successfully translated into community programs and result in similar benefits for physical functioning. PURPOSE: The purpose of this study is to measure the effects of the Active Living Every Day program on physical functioning and physical functional limitations in a diverse sample of older adults. METHODS: As a part of the Active for Life initiative, the Council on Aging of Southwestern Ohio implemented Active Living Every Day (ALED), a group-based lifestyle behavior change program designed to increase physical activity. Performance-based physical functioning tests (30-s Chair Stand Test, eight Foot Up-and-Go Test, Chair Sit-and-Reach Test, 30-Foot Walk Test) were administered to participants at baseline and posttest. Baseline to post-program changes in physical functioning and impairment status were examined with repeated measures analysis of covariance. Interactions tested whether change over time differed according to race/ethnicity, body mass index (BMI), and baseline impairment status. RESULTS: Participants significantly increased their performance in all four physical functioning tests. The percentage of participants classified as "impaired" according to normative data significantly decreased over time. Physical functioning improved regardless of BMI, race/ethnicity, or baseline impairment status. CONCLUSIONS: ALED is an example of an evidenced-based physical activity program that can be successfully translated into community programs and result in significant and clinically meaningful improvements in performance-based measures of physical functioning. PMID- 20589489 TI - Is there a bidirectional link between insomnia and burnout? A prospective study in the Swedish workforce. AB - BACKGROUND: Insomnia and burnout have been suggested to form a bidirectional association. PURPOSE: The aim of this study was to investigate whether there is a bidirectional relationship between insomnia and burnout over the course of a year among individuals in the workforce. METHOD: This study employed a prospective design, where a randomly selected sample from the general population (20-60 year; N = 1,812) filled out a survey on insomnia and burnout. In employed participants (n = 1,258), the associations between insomnia and three dimensions of burnout (Maslach Burnout Inventory-General Survey) were examined while controlling for age, gender, anxiety, and depression. RESULTS: The bivariate correlations between insomnia and the three burnout dimensions were significant at a low level (eta 0.12-0.29). The longitudinal analyses demonstrated that insomnia was not associated with the incidence of burnout and vice versa. However, insomnia was demonstrated to increase the risk for the persistence of emotional exhaustion (OR = 3.02). Further, insomnia was not associated with the persistence of professional efficacy and cynicism, and burnout was not related to the persistence of insomnia. CONCLUSION: In summary, this investigation demonstrated that insomnia and burnout are not bidirectionally related in the working population. While insomnia was linked to the maintenance of the central part of burnout, burnout was not related to future insomnia. PMID- 20589490 TI - Squamous cell carcinoma antigen 1 and 2 expression in cultured normal peripheral blood mononuclear cells and in vulvar squamous cell carcinoma. AB - Squamous cell carcinoma antigen (SCCA) is expressed in normal squamous cell epithelia and in squamous cell carcinomas (SCC). Two nearly identical genes encode the inhibitory serpins SCCA1 (SERPINB3) and SCCA2 (SERPINB4). Serum levels of SCCA are elevated in patients with benign skin diseases and in patients with SCC. SCCA, used for the monitoring of SCC patients, presents no satisfactory diagnostic specificity. As we have shown previously, the reverse transcription polymerase chain reaction (RT-PCR)-based SCCA messenger RNA (mRNA) testing aimed at detecting disseminated cancer cells may be hampered by the false-positive results due to SCCA expression in activated peripheral blood mononuclear cells (PBMC). The aim of this study was to assess the expression of SCCA at mRNA and protein levels in cultured normal PBMC, compared to that in vulvar SCC (VSCC) samples. High SCCA concentrations were found in vulvar tumours and in metastatic lymph nodes, while negative inguinal lymph nodes from the same patients often presented significantly less SCCA. In normal activated PBMC, the level of SCCA protein was the lowest. At the mRNA level SCCA was detectable in normal PBMC even in cultures with no mitogen stimulation, but only by the nested RT-PCR, contrary to VSCC samples found to be SCCA positive already in one-step PCR. Both SCCA1 and SCCA2 transcripts were present in cultured PBMC; SCCA1 was expressed at a higher level than SCCA2. In conclusion, both SCCA forms are detectable in normal PBMC cultured in vitro. SCCA expression level in normal PBMC is much lower than in the squamous epithelium-derived cells. In VSCC, in addition to tumour itself, metastatic lymph nodes seem also to be a potential source of serum SCCA. PMID- 20589491 TI - A new pharmacological approach to gastrointestinal cancer at high risk of relapse based on maintenance of the cytostatic effect. AB - In metastatic colorectal and other locally advanced gastrointestinal cancers, the mechanisms of tumor growth and/or immune escape by residual cancer cells after curative resection often provoke tumor recurrence. Current adjuvant therapy is based on pharmacological administration up to 6-8 months after surgery. We hypothesized that the long-term, cytostatic action from repeated post-adjuvant administration of 5-fluorouracil (FU)-leucovorin (LV) cycles, as a result of the downregulation of the above-mentioned cellular mechanisms, could halt tumor progression. An active prospective cohort, including 19 patients (study group) at high risk of relapse, was considered. All patients received repeated post adjuvant administration of 5-FU-LV cycles for up to 52-60 months following curative surgery (total cumulative dose of about 90 g and mean follow-up of 70.6 +/- 49.7 months). The 5-year disease-free interval (DFS) and overall survival (OS) were 80.4 +/- 10.2% and 87.1 +/- 8.6%, respectively, which is very different from the recent literature that has reported 5-year DFS and OS values of 31.8% and 40.1%, respectively. These findings suggest that this new pharmacological approach based on the long-term maintenance of a cytostatic effect with 5-FU-LV can produce a relevant improvement in the outcome of this population. PMID- 20589492 TI - Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats. AB - RATIONALE: Stress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown. OBJECTIVE: We examined the effects of maternal absence on structure and function of the hippocampus in female offspring. METHODS: We studied whether 24 h of maternal deprivation (MD) on postnatal day 3 altered adult neurogenesis, individual neuronal morphology and dentate gyrus (DG) structure in young adult female rats. In addition, functional alterations were addressed by studying synaptic plasticity in vitro, and spatial as well as emotional learning was tested. RESULTS: Adult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their dendritic arrangement. No effects on the rate of adult neurogenesis were found. Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions. In addition, spatial learning and contextual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala dependent fear memory. CONCLUSION: Although early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers. This may be relevant for the reduced hippocampal volume observed in depression and the increased vulnerability of women to develop depression. PMID- 20589493 TI - GABA(A) receptors in the dorsal raphe nucleus of mice: escalation of aggression after alcohol consumption. AB - RATIONALE: The dorsal raphe nucleus (DRN), the origin for serotonin (5-HT) in forebrain areas, has been implicated in the neural control of escalated aggression. Gamma aminobutyric acid type-A (GABA(A)) and type-B (GABA(B)) receptors are expressed in the DRN and modulate 5-HT neuronal activity, and both play a role in the behavioral effect of alcohol. OBJECTIVE: The purpose of this study is to examine the interaction between drugs acting on GABA receptors in the DRN and alcohol in their effects on aggressive behaviors. METHOD: Male CFW mice, housed with a female, were trained to self-administer ethanol (1.0 g/kg) or water via an operant conditioning panel in their home cage. Immediately after they drank either ethanol or water, the animals were microinfused with a GABAergic drug into the DRN, and their aggressive behaviors were assessed 10 min later. Muscimol (0.006 nmol), a GABA(A) receptor agonist, escalated alcohol-heightened aggression but had no effect in the absence of ethanol. This effect of muscimol was prominent in the animals that showed alcohol-heightened aggression, but not the animals that reduced or did not change aggressive behavior after ethanol infusion compared to water. On the other hand, the GABA(B) agonist baclofen (0.06 nmol) increased aggressive behavior similarly in both water and ethanol conditions. Antagonists of the GABA(A) and GABA(B) receptors, bicuculline (0.006 nmol) and phaclofen (0.3 nmol) respectively, did not suppress heightened aggressive behavior induced by ethanol self-administration. CONCLUSION: GABA(A) receptors in the DRN are one of the neurobiological targets of alcohol-heightened aggression. Activation of the GABA(B) receptors in the DRN also produced escalated aggression, but that is independent of the effect of alcohol. PMID- 20589494 TI - Physical dependence potential of daily tramadol dosing in humans. AB - RATIONALE: Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. OBJECTIVES: The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. METHODS: Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. RESULTS: Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. CONCLUSIONS: Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance. PMID- 20589495 TI - A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity. AB - RATIONALE: Neuronal nitric oxide synthase (NOS1) knockout results in increased impulsive aggression in mice under adverse housing conditions. In line with this, we have previously shown that a functional promoter polymorphism of NOS1, termed NOS1 ex1f-VNTR, is associated with impulsivity-related traits and related disorders. OBJECTIVE: This study aims to examine whether adverse environment interacts with the risk allele on impulsivity-related measures. METHODS: We here studied a population-based cohort of Estonian pupils, recruited at the age of 9 years and followed up for another 9 years. For 435 subjects, measures on impulsivity (Adaptive and Maladaptive Impulsivity Scale, BIS-11, Stop Signal data, and Visual Comparison Test, VCT), environmental conditions (stressful life events and family environment), and NOS1 ex1f-VNTR genotype were available. RESULTS: We found a genotype main effect in that presence of a short NOS1 ex1f VNTR allele was associated with higher levels of adaptive impulsivity, especially in males, but also worse performance in the VCT and the Stop Signal test. Both stressful life events as well as adverse family environment interacted with the risk genotype to increase maladaptive impulsivity. CONCLUSIONS: This study provides further evidence that short alleles of NOS1 ex1f-VNTR go along with impulsive behavior. In the absence of adverse environmental conditions, this may lead to a beneficial effect as functional forms of impulsivity are affected. This however is reversed under negative conditions, as dysfunctional impulsivity is increased under these circumstances. This data provides evidence that NOS1 ex1f VNTR is subject to balancing selection potentially explaining persistence of the risk allele in the population. PMID- 20589496 TI - Effects of antidepressants on the performance in the forced swim test of two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. AB - INTRODUCTION: The selective breeding of Roman low-avoidance (RLA) and high avoidance (RHA) rats for, respectively, poor versus rapid acquisition of active avoidance in a shuttle-box has produced two phenotypes that differ drastically in the reactivity to stressful stimuli: in tests used to assess emotionality, RLA rats display passive ("reactive") coping and robust hypothalamus-pituitary adrenal (HPA) axis reactivity, whereas RHA rats show proactive coping and blunted HPA axis responses. The behavioral and neuroendocrine traits that distinguish these lines suggest that RLA rats may be prone, whereas RHA rats may be resistant to develop depression-like behavior when exposed to stressful experimental conditions. OBJECTIVE AND METHODS: To evaluate the performance of the Roman lines in the forced swim test, immobility, climbing, and swimming were assessed under baseline conditions (i.e., pretest in naive animals or test after the administration of vehicle), and after subacute treatment with desipramine, fluoxetine, and chlorimipramine. RESULTS: Under baseline conditions, RLA rats displayed greater immobility and fewer climbing counts than RHA rats. In RLA rats, desipramine, fluoxetine, and chlorimipramine decreased immobility; moreover, desipramine and chlorimipramine increased climbing, whereas fluoxetine increased swimming. In RHA rats, none of these drugs affected immobility, swimming, or climbing. CONCLUSIONS: RLA and RHA rats represent two divergent phenotypes respectively susceptible and resistant to display depression-like behavior in the forced swim test. Hence, comparative studies in these lines may help to develop novel working hypotheses on the relationships among genotype, temperament traits, and neural mechanisms underlying the vulnerability or resistance to stress-induced depression in humans. PMID- 20589497 TI - Arthroscopic all-inside meniscal repair--Does the meniscus heal? A clinical and radiological follow-up examination to verify meniscal healing using a 3-T MRI. AB - OBJECTIVE: The purpose of this study was to correlate clinical and radiological results using a 3-T MRI to verify meniscal healing after arthroscopic all-inside meniscus repair. MATERIALS AND METHODS: We selected 27 patients (14 men and 13 women) with an average age of 31 +/- 9 years and retrospective clinical examinations and radiological assessments using a 3-T MRI after all-inside arthroscopic meniscal repair were conducted. Repair of the medial meniscus was performed in 19 patients and of the lateral meniscus in eight. In 17 patients (63%), we performed concomitant anterior cruciate ligament reconstruction. The mean follow-up period was 4.5 +/- 1.7 years. The Lysholm score and Tegner activity index were used for clinical evaluation. Four grades were used to classify the radiological signal alterations within the meniscus: central globular (grade 1); linear horizontal or band-like (grade 2); intrameniscal alterations and linear signal alterations communicating with the articular surface (grade 3); and complex tears (grade 4). RESULTS: At follow-up, the average Lysholm score was 76 +/- 15 points, with ten of the patients placed in group 6 based on the Tegner activity index. MRI examinations revealed no signal alteration in three patients, grade 1 in 0, grade 2 in five, grade 3 in 13, and grade 4 in six. The MRI findings correlated positively with the clinical scores in 21 patients (78%). CONCLUSIONS: Correlation of clinical and radiological examination was performed using 3-T MRI. In spite of satisfactory clinical outcomes at follow-up, a radiological signal alteration may still be visible on MRI, which was believed to be scar tissue, but could not be proven definitively. Imaging with a 3-Tesla MRI after meniscal suture surgery provides good but no definitive reliability on meniscus healing and therefore gives no advantage compared to 1.5-T MRI, with good clinical outcome using an all-inside arthroscopic meniscal repair. CLINICAL RELEVANCE: 3T-MRI can not substitute diagnostic arthroscopy in patients with persistent complaints after arthroscopic all-inside meniscal repair. PMID- 20589498 TI - Experience using the thoracodorsal artery perforator flap in axillary hidradentitis suppurativa cases. AB - Hidradenitis suppurativa is a chronic and recurrent inflammatory disease of the apocrine glands characterized by recurrent abscesses, draining sinus tracts, and scarring that can be located in the groin, axilla, perineal, and perianal areas and less frequently in the scalp area. The chronic and relapsing nature of hidradenitis suppurativa leads to physical and psychological damage because it frequently causes disabling pain, diminished range of motion, and social isolation. Surgical removal of all apocrine glands in the affected region is the definitive treatment because conservative treatment usually does not prevent recurrence of hidradenitis suppurativa. The resultant defect can be either left to heal secondarily or closed primarily. Secondary healing in the axilla may cause contractures and stiffening of the shoulder. Primary healing requires direct closure, split-skin grafting, or locoregional flap transposition. The majority of the listed surgical procedures cause long hospital stays and leave contour defects in both the axilla and the arm. This report presents a series of 16 cases managed between March 2006 and June 2008. All the patients had endured a long period of medical treatment and subsequently required surgery for long-term relief of symptoms. The functional and aesthetic outcomes were very satisfactory in all cases despite the final scar. The initial reconstructive aims were achieved for these patients. The authors consider the thoracodorsal artery perforator flap a useful option for the surgical treatment of axillary hidradenitis suppurativa. PMID- 20589499 TI - Lateral brow lift: a surgical proposal. AB - BACKGROUND: In search of alternative techniques for lateral brow lifts in an attempt to offer a less traumatic procedure with lasting results, we developed a simple technique for a lateral brow lift (LBL) that involves suspending the lateral portion of the frontalis muscle. It replaces raising the temporal flap in a conventional face-lift. METHODS: We present a description of the technique and review the histories of 71 patients who underwent this procedure in a private practice from 2002 to 2008. The technique may have been combined with a blepharoplasty or face-lift. RESULTS: The mean operative time was 20 min. Postoperative edema lasted 2 days. We obtained optimal results in 93% of the patients at postoperative month 6. There were complications in 10% of the cases, the most frequent of which was recidivism. No alopecia, paralysis, or vascular complications were observed. CONCLUSION: Our technique is safe and versatile and produces good results, which makes it an excellent choice in the surgical armamentarium of facial rejuvenation. PMID- 20589503 TI - Comment to the paper: Extended endoscopic endonasal approach to the suprasellar parachiasmatic cisterns: anatomic study by Abuzayed Bashar. PMID- 20589501 TI - Two-photon microscopy in pulmonary research. AB - As the lung is constantly exposed to both innocuous and potentially noxious antigens, a thorough understanding of both innate and adaptive immune responses in this organ is of the essence. Imaging modalities such as magnetic resonance imaging, positron emission tomography, and confocal microscopy have expanded our knowledge about various molecular processes and cellular responses in the lung. Two-photon microscopy has evolved into a powerful tool to observe cellular interactions in real time and has markedly expanded our understanding of the immune system. Recently, two-photon microscopy has also been utilized to image the murine lung. As immune responses in the lung differ from those in other non lymphoid tissues, this technique holds great promise to advance our knowledge of the biology that underlies a wide spectrum of pulmonary diseases. PMID- 20589504 TI - Neuroendocrine carcinomas of the larynx: what do the different histologic types really mean? PMID- 20589500 TI - Autophagy and tumorigenesis. AB - Autophagy, a catabolic process involved in the sequestration and lysosomal degradation of cytoplasmic contents, is crucial for cellular homeostasis. The current literature supports that autophagy plays diverse roles in the development, maintenance, and progression of tumors. While genetic evidence indicates autophagy functions as a tumor suppressor mechanism, it is also apparent that autophagy can promote the survival of established tumors under stress conditions and in response to chemotherapy. In this review, we discuss the mechanisms and the evidence underlying these multifaceted roles of autophagy in tumorigenesis, the prospects for targeting autophagy in cancer therapy, and overview the potential markers that may be utilized to reliably detect autophagy in clinical settings. PMID- 20589505 TI - Voice and speech outcomes of chemoradiation for advanced head and neck cancer: a systematic review. AB - Purpose of this review is to systematically assess the effects on voice and speech of advanced head and neck cancer and its treatment by means of chemoradiotherapy (CRT). The databases Medline, Embase and Cochrane were searched (1991-2009) for terms head and neck cancer, chemoradiation, voice and speech rehabilitation. Twenty articles met the inclusion criteria, whereof 14 reported on voice outcomes and 10 on speech. Within the selected 20 studies, 18 different tools were used for speech or voice evaluation. Most studies assessed their data by means of patient questionnaires. Four studies presented outcome measures in more than one dimension. Most studies summarised the outcomes of posttreatment data that were assessed at various points in time after treatment. Except for four studies, pre-treatment measurements were lacking. This and the fact that most studies combined the outcomes of patients with radiated laryngeal cancers with outcome data of non-laryngeal cancer patients impedes an interpretation in terms of the effects of radiation versus the effects of the disease itself on voice or speech. Overall, the studies indicated that voice and speech degenerated during CRT, improved again 1-2 months after treatment and exceeded pre-treatment levels after 1 year or longer. However, voice and speech measures do not show normal values before or after treatment. Given the large-ranged posttreatment data, missing baseline assessment and the lacking separation of tumour/radiation sites, there is an urgent need for structured standardised multi-dimensional speech and voice assessment protocols in patients with advanced head and neck cancer treated with CRT. PMID- 20589506 TI - Functional and esthetic assessment of radial forearm flap donor site repaired with split thickness skin graft. AB - The purpose of this study was to evaluate the long-term functional and esthetic outcomes of radial forearm flap (RFF) donor site repaired with split thickness skin graft (STSG). Nineteen patients underwent surgical reconstruction of oro facial defects by the use of RFF and their donor sites were reconstructed with STSG. The patients were followed up at least for 12 months postoperatively and the left hand was the non-dominant hand in all of them. Objective methods including pinch strength, grip strength, range of motion, current perception threshold (CPT) and two-point discrimination, and subjective methods including patients interview, visual analogue score (VAS) about function, sensitivity, pain and color match, were collectively employed for donor site assessment. Our data revealed some degree of reduction in motor function and sensation compared to the non-donor hand. The difference of pinch strength means was 9.81% and of the grip strength was 12.6%. The difference of wrist flexion means was 17.6% and of wrist extension was 13.4%. However, none of the patients had functional defects of forearm supination and pronation, wrist ulnar deviation or wrist radial deviation. Subjective evaluation showed that the donor site repaired with STSG was well accepted by the patients particularly from a functional point of view. These results demonstrate that STSG represents a favorable choice for RFF donor site repair. PMID- 20589507 TI - Childhood adversity and chronicity of mood disorders. AB - To evaluate the potential impact of early childhood problems on the chronicity of mood disorders. A representative cohort from the population was prospectively studied from ages 19/20 to 39/40. Unipolar (UP) and bipolar disorders (BP) were operationally defined applying broad Zurich criteria for bipolarity. Chronicity required the presence of symptoms for more days than not over 2 years prior to an interview, or almost daily occurrence for 1 year. A family history and a history of childhood problems were taken at ages 27/28 and 29/30. Data include the first of multiple self-assessments with the Symptom-Checklist-90 R at age 19/20, and mastery and self-esteem assessed 1 year later. A factor analysis of childhood problems yielded two factors: family problems and conduct problems. Sexual trauma, which did not load on either factor, and conduct problems were unrelated to chronicity of UP or BP or both together. In contrast, childhood family problems increased the risk of chronicity by a factor of 1.7. An anxious personality in childhood and low self-esteem and mastery in early adulthood were also associated with chronicity. Childhood family problems are strong risk factors for the chronicity of mood disorders (UP and BP). The risk may be mediated partly by anxious personality traits, poor coping and low self-esteem. PMID- 20589508 TI - Compact internal representation of dynamic situations: neural network implementing the causality principle. AB - Animals for survival in complex, time-evolving environments can estimate in a "single parallel run" the fitness of different alternatives. Understanding of how the brain makes an effective compact internal representation (CIR) of such dynamic situations is a challenging problem. We propose an artificial neural network capable of creating CIRs of dynamic situations describing the behavior of a mobile agent in an environment with moving obstacles. The network exploits in a mental world model the principle of causality, which enables reduction of the time-dependent structure of real situations to compact static patterns. It is achieved through two concurrent processes. First, a wavefront representing the agent's virtual present interacts with mobile and immobile obstacles forming static effective obstacles in the network space. The dynamics of the corresponding neurons in the virtual past is frozen. Then the diffusion-like process relaxes the remaining neurons to a stable steady state, i.e., a CIR is given by a single point in the multidimensional phase space. Such CIRs can be unfolded into real space for execution of motor actions, which allows a flexible task-dependent path planning in realistic time-evolving environments. Besides, the proposed network can also work as a part of "autonomous thinking", i.e., some mental situations can be supplied for evaluation without direct motor execution. Finally we hypothesize the existence of a specific neuronal population responsible for detection of possible time-space coincidences of the animal and moving obstacles. PMID- 20589509 TI - Modeling the electric image produced by objects with complex impedance in weakly electric fish. AB - Weakly electric fish generate an electric field around their body by electric organ discharge (EOD). By measuring the modulation of the electric field produced by an object in the field these fish are able to accurately locate an object. Theoretical and experimental studies have focused on the amplitude modulations of EODs produced by resistive objects. However, little is known about the phase modulations produced by objects with complex impedance. The fish must be able to detect changes in object impedance to discriminate between food and nonfood objects. To investigate the features of electric images produced by objects with complex impedance, we developed a model that can be used to map the electric field around the fish body. The present model allows us to calculate the spatial distribution of the amplitude and phase shift in an electric image. This is the first study to investigate the changes in amplitude and phase shift of electric images induced by objects with complex impedance in wave-type fish. Using the model, we show that the amplitude of the electric image exhibits a sigmoidal change as the capacitance and resistance of an object are increased. Similarly, the phase shift exhibits a significant change within the object capacitance range of 0.1-100 nF. We also show that the spatial distribution of the amplitude and phase shifts of the electric image resembles a "Mexican hat" in shape for varying object distances and sizes. The spatial distribution of the phase shift and the amplitude was dependent on the object distance and size. Changes in the skin capacitance were associated with a tradeoff relationship between the magnitude of the amplitude and phase shift of the electric image. The specific range of skin capacitance (1-100 nF) allows the receptor afferents to extract object features that are relevant to electrolocation. These results provide a useful basis for the study of the neural mechanisms by which weakly electric fish recognize object features such as distance, size, and impedance. PMID- 20589510 TI - Endoscopic enucleation for gastric subepithelial tumors originating in the muscularis propria layer. AB - BACKGROUND: Subepithelial tumors (SETs) of the stomach are considered benign. However, they have the potential for malignant transformation, especially if they originate in the muscularis propria layer. This study aimed to determine the feasibility of endoscopic enucleation (EEN) for SETs in the muscularis propria layer and to evaluate the diagnostic efficacy and safety of EEN for SETs. METHODS: A total of 65 lesions in 64 patients were eligible for inclusion in the study during the period between June 2006 and September 2009. En bloc enucleation using an insulated-tip knife and snare was attempted for removal of gastric SETs from the muscularis propria. RESULTS: A total of 60 tumors were successfully resected by EEN (success rate, 92.3%). The mean tumor size, determined by endoscopic ultrasound, was 13.8 mm (range, 5-30 mm). A histologic diagnosis was obtained for 63 tumors (diagnostic yield, 96.9%), which was leiomyoma for 32 lesions, gastrointestinal stromal tumor for 26 tumors, and other for 5 tumors. The rate for complete resection in relation to the location of the lesion in the stomach was higher for the cardia, the mid/lower body (100%), and the high body (96%) than for the fundus (75%) or the antrum (50%, p=0.006). The rate of perforation was significantly higher for the fundus (50%) than for other locations (0% for the cardia and 4% for the high body) (p<0.001). CONCLUSIONS: Endoscopic enucleation of gastric SETs originating in the muscularis propria layer was a safe and effective method for the histologic diagnosis and removal of small gastric SETs, especially those located in the cardia and the high body of the stomach. PMID- 20589511 TI - Full-thickness endoscopic resection of nonintracavitary gastric stromal tumors: a novel approach. AB - BACKGROUND: Until now, the conventional treatment of stromal tumors has been primarily open surgery or laparoscopic excision. The use of combined laparoscopic/endoscopic surgeries has been investigated, but endoscopic therapy alone has been limited to en bloc resection or nucleus removal of intracavitary tumors with diameters<2 cm. Nonintracavitary and intramural gastric stromal tumors preclude the use of endoscopic resection due to the risk of gastric perforation. This study was designed to show the safety and effectiveness of full thickness endoscopic resection of nonintracavitary stromal tumors based on our direct experience. METHODS: A total of 109 consecutive patients with nonintracavitary gastric stromal tumors<4 cm in diameter underwent surgical treatment; 66 patients received endoscopic surgery and 43 patients received laparoscopic surgery. RESULTS: No significant differences existed between the two groups in terms of demographics and clinical characteristics, and no tumor exceeded 3.5 cm in size. Median operation times (endoscopic group, 53.6 min; laparoscopic group, 139 min) and hospitalization fees of the endoscopic group were significantly lower than those of the laparoscopic group with significant median hospital stays (8 days for endoscopic group; 6 days for laparoscopic group). No intraoperative complications occurred in the laparoscopic group and complete removal of tumors was achieved in the endoscopic group. Postoperative complications occurred in 6 patients of 43 who underwent laparoscopic surgery and 17 patients of 66 who underwent endoscopic surgery, representing a significant difference; the size of the lesion correlated positively with the occurrence of complications. CONCLUSIONS: Endoscopic resection is safe and effective for treating nonintracavitary stromal tumors. The endoscopic natural-cavity technique produced less surgical injury to the patients and preserved the anatomy of intra abdominal structures. In addition, the endoscopic technique reduced operative times, postoperative bleeding, and costs. PMID- 20589512 TI - Ventricular fibrillation caused by electrocoagulation in monopolar mode during laparoscopic subphrenic mass resection. AB - BACKGROUND: Monopolar is usually a safe and effective electrosurgical unit used in laparoscopic general surgery. However, it can cause adverse outcomes and even cardiac arrest. We present a video of laparoscopic subphrenic mass resection using monopolar coagulation during which ventricular fibrillation occurred and from which the patient was successfully resuscitated. METHODS: Our patient was a 39-year-old man who was admitted to our institution for treatment of a liver mass. The mass was located in the left subphrenic region and was 3.31 cm * 2.7 cm according to B ultrasound. He had had a spleen resection after a car accident 14 years before. He was otherwise healthy and a physical examination was negative. He was scheduled for "laparoscopic exploration, mass resection." General anesthesia was induced and the operation began. While dissecting the mass from the diaphragm there was some bleeding; monopolar electrocoagulation with 68 W was performed upon which ventricular fibrillation occurred. The operation was stopped and closed-chest compression began immediately. Defibrillation (200-J shock) was performed in 1 min and rhythm returned to sinus. RESULTS: The operation was resumed carefully and uneventfully. The patient was sent to the postoperative acute care unit and was extubated 10 min after operation. The patient recovered uneventfully without any signs of permanent cardiac injury and was discharged on postoperative day 3. The final pathology was accessory spleen. CONCLUSIONS: We present a video of a patient who experienced ventricular fibrillation during laparoscopic surgery which was successfully defibrillated leaving no permanent cardiac injury. We assume the reason for the ventricular fibrillation was the low frequency leakage current from electrocoagulation which may be conducted by Swan Ganz catheter to the heart. It is important that we be familiar with the character of electrosurgical unit when performing laparoscopic surgery. We should be careful when using an electrosurgical unit near the cardiac region, especially when the patient has an indwelling catheter. We recommend performing hemostasis in bipolar mode or use an ultrasonic scalpel if bleeding is close to the heart. Also, an easily available defibrillator should be ready for use. PMID- 20589513 TI - Early laparoscopy for the evaluation of nonspecific abdominal pain: a critical appraisal of the evidence. AB - BACKGROUND: Patients with nonspecific abdominal pain (NSAP) are frequently seen in emergency departments. Different studies have suggested that early laparoscopy (EL) could be an adequate tool to accelerate diagnosis and therapy. The aim of this study was to assess the effectiveness of EL in terms of diagnosis, persistence of NSAP, mortality, morbidity, cost, hospital stay, and quality of life relative to observation in NSAP. METHODS: We performed a systematic review to identify randomized controlled trials (RTC) comparing EL versus active observation (AO) in NSAP. The primary outcomes were the number of patients with positive and negative findings, the utility for each group, and the cases with persistence of NSAP. Methodologic quality was assessed using the recommendations of the Cochrane Collaboration. RESULTS: Five studies that included a total of 921 patients were included: 460 in the EL group and 461 in the AO group. The use of an important methodologic heterogeneity between included studies avoided a pooled analysis. Data suggested that EL performed better in establishing a final diagnosis (79.2-96.9%) vs. AO (28.1-78.1%); however, the final therapeutic utility of laparoscopy was lower than the diagnostic rate (10.9-86.5%). The mortality rate of EL was similar to AO, and morbidity ranged from 1.15 to 23.72% in EL compared with the range from 1.9 to 31.14% in AO. The length of hospital stay ranged from 1.3 to 4.18 days in EL compared with the range from 2 to 7.3 days in AO. CONCLUSIONS: There is an important heterogeneity between the populations and in the degree of methodologic quality in the included studies. Data suggest that EL performs better in establishing a final diagnosis after admission, but the lack of uniform information does not allow for the recommendation of EL as a routine strategy in clinical practice. We recommend that a large trial be conducted with specific operative characteristics to solve problems identified in primary trials. PMID- 20589514 TI - Analysis of poor outcomes after laparoscopic adjustable gastric banding. AB - BACKGROUND: Recent studies document excess weight loss (EWL) of more than 50% with the laparoscopic adjustable gastric band (LGB). This study reviews the LGB experience at an urban academic center in terms of complications, reoperative rates, and comorbidities. METHODS: In this study, 144 consecutive patients undergoing LGB were prospectively reviewed. Data were collected including weight, body mass index (BMI), excess weight loss (EWL), comorbidities, and complications. Demographics were analyzed using a t-test. Linear regression was used to analyze the relationship of BMI, race, and age to EWL at 12 months. RESULTS: The study participants were 130 women with a mean age of 43 +/- 11 years, a mean weight of 127.1 kg +/- 20.5 kg, and a mean BMI of 45.6 +/- 6.1. The mean follow-up period was 16 months. The mean EWL was 20% +/- 14% at 6 months (n = 118), 26% +/- 16% at 12 months (n = 106), 30% +/- 20% at 18 months (n = 68), and 34% +/- 23% at 24 months (n = 43). Patients with a BMI higher than 50 kg/m(2) had a lower EWL at 12 months than patients with a BMI lower than 50 kg/m(2) (P = 0.00005). The mean EWL at 12 months was significantly less for African Americans than for Caucasians (P = 0.0046; 95% confidence interval [CI] 3-15%). Patients older than 50 years had a lower EWL, but the difference was not statistically significant (P = 0.07). Complete and partial resolution of comorbidities occurred for 10% and 4% of the patients, respectively. Removal of the band with revision to a sleeve gastrectomy for inadequate EWL was required for 14 patients (11.5%). Complications occurred for 8% of the patients (n = 15) including port flipping, stoma obstruction, tube disconnection, port infections, dysphagia, and band slippage. Overall, 16.7% of the patients (n = 24) required reoperation. CONCLUSION: After LGB, a majority of the patients failed to achieve a 50% EWL, and 16.7% required reoperation. Laparoscopic adjustable gastric banding may not be the optimal bariatric procedure for patients older than 50 years, patients with a BMI higher than 50 kg/m(2), or African Americans. PMID- 20589515 TI - Effects of preemptive analgesia in laparoscopic cholecystectomy: a double-blind randomized controlled trial. AB - BACKGROUND: This study aimed to investigate the effect of preemptive etoricoxib compared with placebo in laparoscopic cholecystectomy. METHODS: This randomized, double-blind, placebo-controlled study enrolled 120 patients requiring elective laparoscopic cholecystectomy. The patients were randomized to receive either etoricoxib 120 mg plus diazepam or placebo plus diazepam. Postoperatively, the visual analog score (VAS) for pain, the rescue morphine requirement, and the side effects were recorded. RESULTS: Between February 2006 and September 2007, 120 patients were enrolled in the study. The demographic data between two groups were similar except for mean age. The mean age of the placebo group was younger (p = 0.007). There were no significant differences in bleeding tendency rating scores, duration times between fentanyl and rescue morphine, number of rescue morphine doses, or length of postoperative hospital stay. But the number of oral analgesic drug usages was significantly less in the etoricoxib group (p = 0.006). The postoperative VAS was lower in the etoricoxib group at hours 10 (p = 0.023), 14 (p = 0.045), and 26 (p = 0.011), and the average VAS also was significantly less in the etoricoxib group (p = 0.013). The two groups did not differ significantly in terms of postoperative shoulder pain (p = 0.065). According to the verbal rating scale, the incidence of postoperative nausea and vomiting did not differ significantly between the two groups (p = 0.797), nor did the drug side effects or treatment complications. CONCLUSION: The authors recommend using etoricoxib as a preemptive analgesia to reduce postoperative pain after laparoscopic cholecystectomy. PMID- 20589517 TI - Brown-Sequard syndrome revealing intradural thoracic disc herniation. AB - Brown-Sequard syndrome (BSS) is a rare form of severe myelopathy characterised by a clinical picture reflecting hemisection of the spinal cord. This syndrome is mostly due to a penetrating injury to the spine but many other non-traumatic causes have been described. Intradural thoracic disc herniation (TDH) is one of the rare aetiologies of this syndrome. Despite progress in imaging techniques, diagnosis and treatment remain difficult. We retrospectively reviewed one of the largest reported series of six patients with BSS revealing intradural TDH between 2003 and 2007. There was a marked female predominance and the mean age was 44 years. Before surgery, half of the patients had a severe neurological deficit. The mean duration of symptoms until surgery was 8.5 months (range 0.5-24 months). Spine magnetic resonance imaging (MRI) or spine computer tomography scan showed calcified TDH between T5-T6 and T9-T10. The intradural location of the thoracic herniation was strongly suspected from the clinical data. All the patients underwent posterolateral transpedicular surgery with an operative microscope to open the dura mater. The intradural location of the herniation was overlooked in one case and the patient underwent a second procedure. The dura mater was carefully closed. Two patients' condition worsened immediately after the surgery before slowly improving. All the other patients improved their neurological status immediately after the surgery and at 12 months follow-up. BSS with TDH on the spine MRI scan may be a warning symptom of the intradural location of the herniated disc. In such cases, spine surgeons are advised to use an operative magnification and to open the dura mater to avoid missing this potentially curable cause of severe myelopathy. PMID- 20589518 TI - Anatomical and surgical study of volume determination of the anterolateral epidural space nerve root L5/S1 under the aspect of epidural perineural injection in minimal invasive treatment of lumbar nerve root compression. AB - Herniated intervertebral disc causes in a great number of cases of lumbar nerve root compression, especially in the segment L5/S1. Other reasons responsible for stress to the lumbar spinal root are the spinal canal stenosis and the postdiscotomy syndrome. For patients without neurological deficiencies, the conservative treatment includes different epidural injection techniques. Steroids are often applied. A specific injection technique needing only a small drug amount is the epidural perineural approach using a special two-needle technique. The anatomical spaces of the nerve roots have received little attention in therapy. We have determined the anterolateral epidural space nerve volume of the nerve root L5/S1, and compared the data collected in an anatomical study with operative measurements during discectomy. The volume determination in the human cadavers was performed with liquid silicone filling the anterolateral space after dissection. The in vivo measurements were performed during surgery at the site of the anterolateral space after discectomy. The anatomical studies showed us a mean value volume of 1.1 ml. The surgical volume determinations result in a mean volume of 0.9 ml. A better understanding of the anterolateral epidural space may allow a reduction of the injection volume in the conservative nerve root compression treatment, especially using the epidural perineural technique, avoiding the risk of side effects of high doses of steroids. PMID- 20589516 TI - The stabilizing potential of anterior, posterior and combined techniques for the reconstruction of a 2-level cervical corpectomy model: biomechanical study and first results of ATPS prototyping. AB - Clinical studies reported frequent failure with anterior instrumented multilevel cervical corpectomies. Hence, posterior augmentation was recommended but necessitates a second approach. Thus, an author group evaluated the feasibility, pull-out characteristics, and accuracy of anterior transpedicular screw (ATPS) fixation. Although first success with clinical application of ATPS has already been reported, no data exist on biomechanical characteristics of an ATPS-plate system enabling transpedicular end-level fixation in advanced instabilities. Therefore, we evaluated biomechanical qualities of an ATPS prototype C4-C7 for reduction of range of motion (ROM) and primary stability in a non-destructive setup among five constructs: anterior plate, posterior all-lateral mass screw construct, posterior construct with lateral mass screws C5 + C6 and end-level fixation using pedicle screws unilaterally or bilaterally, and a 360 degrees construct. 12 human spines C3-T1 were divided into two groups. Four constructs were tested in group 1 and three in group 2; the ATPS prototypes were tested in both groups. Specimens were subjected to flexibility test in a spine motion tester at intact state and after 2-level corpectomy C5-C6 with subsequent reconstruction using a distractable cage and one of the osteosynthesis mentioned above. ROM in flexion-extension, axial rotation, and lateral bending was reported as normalized values. All instrumentations but the anterior plate showed significant reduction of ROM for all directions compared to the intact state. The 360 degrees construct outperformed all others in terms of reducing ROM. While there were no significant differences between the 360 degrees and posterior constructs in flexion-extension and lateral bending, the 360 degrees constructs were significantly more stable in axial rotation. Concerning primary stability of ATPS prototypes, there were no significant differences compared to posterior-only constructs in flexion-extension and axial rotation. The 360 degrees construct showed significant differences to the ATPS prototypes in flexion-extension, while no significant differences existed in axial rotation. But in lateral bending, the ATPS prototype and the anterior plate performed significantly worse than the posterior constructs. ATPS was shown to confer increased primary stability compared to the anterior plate in flexion-extension and axial rotation with the latter yielding significance. We showed that primary stability after 2-level corpectomy reconstruction using ATPS prototypes compared favorably to posterior systems and superior to anterior plates. From the biomechanical point, the 360 degrees instrumentation was shown the most efficient for reconstruction of 2 level corpectomies. Further studies will elucidate whether fatigue testing will enhance the benefit of transpedicular anchorage with posterior constructs and ATPS. PMID- 20589519 TI - The results of simultaneous posterior-anterior-posterior surgery in multilevel tuberculosis spondylitis associated with severe kyphosis. AB - We retrospectively studied the cases with tuberculous spondylitis of thoracolumbar region with two or more levels of involvement that underwent posterior instrumentation and fusion and anterior fusion with titanium mesh following anterior decompression using simultaneous successive posterior-anterior posterior surgery. Among all patients with tuberculous spondylitis accompanied by medium or severe kyphosis, 20 patients who underwent simultaneous successive decompression, fusion and instrumentation with posterior-anterior-posterior surgery between 1999 and 2004 were included in the study. Patients were evaluated for fusion formation and neurological and functional status. Kyphosis angles were measured at early and long-term follow-up. Antituberculosis chemotherapy was initiated in all patients and continued for 9 months; initially as quadruple therapy for 3 months, and then as triple therapy. Average follow-up period was 52.7 months (range 37-94). Solid fusion was achieved in all patients. All patients returned to their previous occupation; 75% (15 subjects) with mild pain or no pain and 15% (3 subjects) with major limitations. There were 11 patients with neurological deficit, 9 of these achieved complete neurological recoveries. Regarding kyphosis angle, an average 35.1 degrees correction (84.8%) was obtained in postoperative period (p < 0.001) and there was no significant correction loss during the follow-up period (p < 0.05). There were no grafts or instrumentation-related stabilization problems. In subjects with tuberculous spondylitis with involvements at two or more levels accompanied by medium and severe kyphosis, decompression, fusion and instrumentation by simultaneous successive posterior-anterior-posterior surgery is an effective and safe management method for effective kyphosis correction with high fusion rates. PMID- 20589520 TI - Takayasu's arteritis: clinical features and outcomes of 125 patients in China. AB - Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. The clinical features of TA vary in different ethnic populations. The objective of this study is to characterize the clinical features, angiographic findings, and response to treatment of patients with TA in Changhai Hospital, Shanghai, China. The hospital records of 125 patients diagnosed with TA were retrospectively evaluated. Eighty patients were followed for a median duration of 36 months. Females (86.4%) were most frequently affected. The mean age at onset was 26.9 years. Constitutional symptoms were present in only 38.4% of patients. The most common clinical finding was pulse deficit. Histological findings from 12 clinically inactive patients showed active lesions in 58.3%. Angiographic classification showed that type I was the most common, followed by type V and IV. Type I was more common in adult patients than in pediatric patients. Although immunosuppressive treatment induced remission in most patients, over 90% of those who achieved later remission relapsed. Both bypass procedures and angioplasty showed high rates of initial success, but restenosis occurred in 34.7% of bypass procedures and 77.3% of angioplasty procedures. Eight patients died during the follow-up period with the main cause of death being congestive heart failure. Constitutional symptoms were not frequent in our study. Correlation between the clinical assessment of disease activity and histologic findings is often poor in TA. Angiographic findings showed that type I was the most common in our study. Over the longer term, the outcomes of revascularization were superior to angioplasty. PMID- 20589521 TI - Single-incision laparoscopic surgery for right hemicolectomy: our initial experience with 10 cases. AB - BACKGROUND: Published data has confirmed the oncological safety and efficacy of laparoscopic colorectal surgery. Continued surgical innovation has seen the recent resurgence of single-port laparoscopic surgery. We present a series of 10 cases of single-incision laparoscopic surgery (SILS) for right hemicolectomy, with the aim of reaffirming the feasibility and favourable short-term results of this technique. METHODS: Ten patients underwent SILS for right hemicolectomy using the SILS port, between June 2009 and August 2009. A longitudinal periumbilical incision was used as the access point for all cases. Data analysed included age, gender, American Society of Anaesthesiology score, body mass index (BMI), location of disease, duration of surgery, length of incision and duration of hospital stay. Inclusion criteria were no prior abdominal surgery, no intra abdominal sepsis, no distant metastases and a BMI of <30. RESULTS: All 10 cases of right hemicolectomy were successfully performed using the SILS port through a single periumbilical incision. The median age of patients was 64 years (range 48 83 years), with a median body mass index of 21.5 kg/m(2) (range 18.9-25.6 kg/m(2)). The median duration of surgery and hospital stay was 83 min (range 60 125 min) and 6 days (range 5-11 days), respectively. No morbidity or mortality was associated with this technique, and all patients recovered uneventfully. CONCLUSION: This case series illustrates that SILS for right hemicolectomy is feasible and safe. However, the routine use of this innovative technique in malignant disease cannot be recommended without further large-scale prospective trials. PMID- 20589522 TI - Long-term protection against hepatitis B after newborn vaccination: 20-year follow-up. AB - BACKGROUND: Hepatitis B vaccination in children born to hepatitis B surface antigen (HBsAg)-positive mothers considerably decreases the risk of vertical transmission. However, whether this protection against carriage of hepatitis B virus is maintained into early adulthood is as yet unknown. PATIENTS AND METHODS: A combined passive-active immunization programme for newborns of HBsAg-positive mothers was initiated in the north-eastern part of the Czech Republic in 1988. The number of immunized newborns had reached 665 newborns by the end of 2006. All mothers of immunized infants were HBsAg-positive during pregnancy, and 34 (5%) were also hepatitis B e antigen (HBeAg)-positive. The immunization programme consists of providing newborns with protection at birth with hepatitis B immunoglobulin, followed by three 10-MUg doses of plasma-derived or, since 1990, recombinant vaccine administered at 0, 1 and 6 months of life. Only 29 children of HBeAg-positive mothers received vaccine at 0, 1 and 2 months of life. Blood samples were obtained after immunization, at 2 years of age, and biennially thereafter. Samples were tested for HBsAg and hepatitis B surface and core antibodies (anti-HBs, anti-HBc). RESULTS: The immunization schedules were completed in 640 children. A protective anti-HBs level after immunization was proven in 574 of 620 children (93%). Persistence of protective anti-HBs antibodies was detected in 70, 40 and 25% of children at 5, 10 and 15 years of age. Vertical transmission with chronic HBsAg carrier status was detected in two infants. Anti-HBc seroconversion was proven in ten children from 3 to 15 years of age. Natural boosting with an anti-HBs increase was detected in 38 children (twice in one child). CONCLUSION: Our results show that combined active-passive immunization of newborns against hepatitis B provides persistent protection up to adolescence despite a frequent waning of anti-HBs antibodies, suggesting there is no need for booster vaccination during adolescence. PMID- 20589523 TI - Impact of herpes simplex virus detection in respiratory specimens of patients with suspected viral pneumonia. AB - BACKGROUND: Respiratory infection and failure is a commonly encountered problem in intensive care unit (ICU) patients. However, despite the accumulating body of evidence to suggest that herpes simplex virus type 1 (HSV-1) is associated with pneumonia, the exact role played by this virus in this process is still not fully understood. Therefore, to identify patients at risk, we have conducted a case control study to characterize patients with HSV-1-positive pneumonia. PATIENTS AND METHODS: Between 2007 and 2009, all patients with suspected viral pneumonia were tested for the presence of herpes viruses using a PCR assay approach with respiratory specimens. To identify possible associations, risk factors, and impact of HSV, HSV-1-positive ICU patients (n = 51) were compared to age-, gender , and department- and season-matched HSV-negative patients (n = 52). RESULTS: HSV positive patients differed significantly from the HSV-negative ones only in terms of time of mechanical ventilation (13 vs. 6 days, respectively; p = 0.002). Subgroup analysis in the patients aged >60 years and in those without bacterial detection revealed a similar trend (p = 0.01 and p = 0.004, respectively). Mortality did not differ between the groups or between the HSV-1-positive patients treated with aciclovir and those who were not. A viral load >10E+05 geq/ml was associated with mechanical ventilation (20/21 vs. 17/29; p = 0.004), acute respiratory distress syndrome (ARDS; 19/21 vs. 18/29; p = 0.005), sepsis (18/21 vs. 14/29; p = 0.008), detection of a bacterial pathogen in the same specimen (10/21 vs. 4/29; p = 0.01) and longer ICU stay (25 vs. 30 days; p = 0.04). CONCLUSION: Despite several associations with high viral load, the clinical outcome of HSV-1-positive ICU patients did not differ significantly from the clinical outcome of HSV-negative patients. This finding indicates that HSV-1 viral loads in respiratory specimens are a symptom of a clinically poor condition rather than a cause of it. Longitudinal and therapy studies are therefore needed to distinguish between HSV-1 as a causative pathogen and HSV-1 as a bystander of pneumonia/ARDS. PMID- 20589524 TI - Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States. AB - Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P < 0.001). Because increased numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation. PMID- 20589525 TI - Inhibition of the JAK-2/STAT3 signaling pathway impedes the migratory and invasive potential of human glioblastoma cells. AB - The objective of current treatment strategies for glioblastoma (GBM) is cytoreduction. Unfortunately, the deleterious migratory and invasive behavior of glial tumors remains largely unattended. The transcription factor signal transducer and activator of transcription (STAT) 3 is known to be involved in the development and progression of many different tumor types, including malignant gliomas. Beside other biological effects, STAT3 controls cell proliferation and tissue remodeling, processes common to both wound healing and tumor dissemination. Here, we report on impeded migratory and invasive potential of five different glioblastoma cell lines after treatment with AG490, a pharmacological inhibitor of the upstream STAT3 activator Janus kinase (JAK) 2. STAT3 was constitutively activated in all the cell lines tested, and treatment with AG490 eliminated the biologically active, tyrosine705-phosphorylated form of STAT3 in a dose-dependent fashion, as determined by Western blot analysis. Inhibition of activated STAT3 was paralleled by a decrease in transcriptional expression of the STAT3 target genes MMP-2 and MMP-9, and led to reduced proteolytic activity, as determined by zymography. Accordingly, the migratory behavior of all five GBM cell lines was impeded in monolayer wound-healing assays; invasive capacity in matrigel-coated trans-well assays was also hampered by treatment with AG490. The proliferative activity of the cell lines was also significantly reduced after treatment with AG490. The effects elicited by STAT3 inhibition were observed in both PTEN-expressing and PTEN-deficient cells. Because pharmacological inhibition of the JAK-2/STAT3 signaling pathway affects not only tumor cell proliferation but also the characteristic features of malignant gliomas, i.e. migration and invasion pertinent to invariable tumor recurrence and high morbidity, our findings support the idea that STAT3 is a suitable target in the treatment of brain tumors. PMID- 20589526 TI - Inhibitory effect of anti-aminopeptidase N/CD13 antibodies on fibroblast migration. AB - Aminopeptidase N (APN)/CD13 is a widely expressed transmembrane ectoenzyme and has been implicated in a myriad of physiological processes that are specific to cell type and tissue origin, including cancer cell metastasis, angiogenesis, cholesterol uptake, apoptosis, and cell migration. Skin cells, in particular fibroblasts have a relatively high level of APN/CD13 expression. The migratory capacity of skin cells is critical for the outcome of wound repair, as successful wound healing requires timely re-epithelialization which involves reformation of epithelium over wound surface by migrating keratinocytes. While failure of keratinocytes to undergo proper migration leads to chronic non-healing wounds, the presence of excess fibroblasts may contribute to formation of hypertrophic scars and keloids. The aim of this study was to investigate the role of APN/CD13 in skin cell migration and explore its potential as a therapeutic target in wound healing. Our results show an elevated expression of APN/CD13 in fibroblasts on the edge of the wound compared to unwounded cells. The presence of anti-APN/CD13 antibodies WM15, 3D8, and H300 reduces the migratory activity of human dermal fibroblasts in a dose-dependent manner by 42, 21, and 28%, respectively. However, the antibodies have no effect on keratinocyte migration. Further, none of the anti-APN/CD13 antibodies used in this study has any antiproliferative and cytotoxic effect on primary human keratinocytes or fibroblasts when used at 10 MUg/ml in vitro. The differential inhibition on the migratory capacity of fibroblasts and keratinocytes presents an opportunity for anti-APN/CD13 antibodies to be used as a therapeutic agent for high fibroblast cellularity seen in fibroproliferative disorders. PMID- 20589527 TI - Comparison of EMSA and SPR for the characterization of RNA-RNase II complexes. AB - RNases are enzymes that process and degrade RNA molecules. As such, the study of the interactions between these enzymes and RNA molecules is essential in order to better understand their mechanism of action. In this report, our aim was to use E. coli RNase II as a model to compare two different techniques for the characterization and interpretation of the stability of RNA-protein complexes: Surface Plasmon Resonance and Electrophoretic Mobility Shift Assay. PMID- 20589529 TI - Spatial mobility, alcohol use, sexual behavior and sexual health among males in India. AB - This paper examines the linkages of permanent migration, temporary mobility and alcohol consumption with risky sexual behavior and sexually transmitted infections (STIs) including HIV infection among males in India using a nationally representative dataset. The study shows that non-migrant men and migrant men do not differ significantly in any indicator of risky sexual behavior and STIs. Temporary long duration mobile men reported significantly more often than the non mobile men or short duration mobile men that they had sex with multiple sex partners during their lifetime as well as sex with a high risk partner and had paid sex in the 12 months preceding the survey. Males who drank alcohol almost every day notwithstanding with their migration or mobility status were most prone to lifelong as well as more recent sexual risk behavior. Controlling for sociodemographic characteristics long duration mobile men and men who used alcohol almost daily had higher sexual risk behaviors and STI infections. Further migration and mobility did not show any significant relationship with tested HIV prevalence among males in India, controlling for sociodemographic characteristics. Males who had lifetime multiple sex partners were at the highest risk of tested HIV infection controlling for sociodemographic characteristics, migration, mobility, alcohol use and STI infection. Interventions focusing on HIV prevention in India need to target both non-migrant and migrant men, particularly those who drink alcohol more frequently or daily. Targeted interventions are required for temporary mobile men, particularly for those mobile men who have to stay away from their homes continuously for a longer duration. Long duration mobile men are most prone to regular alcohol use and risky sexual behavior. PMID- 20589528 TI - Adaptation of an alcohol and HIV school-based prevention program for teens. AB - Given the current status of HIV infection in youth in India, developing and implementing HIV education and prevention interventions is critical. The goal for School-based Teenage Education Program (STEP) was to demonstrate that a HIV/AIDS and alcohol abuse educational program built with specific cultural, linguistic, and community-specific characteristics could be effective. Utilizing the Train the-Trainer model, the instructors (17-21 years) were trained to present the 10 session manualized program to primarily rural and tribal youth aged 13-16 years in 23 schools (N = 1,421) in the northern state of Himachal Pradesh in India. The intervention had a greater impact on girls; girls evidenced greater communication skills and a trend towards greater self efficacy and reduced risk taking behavior. The STEP has been successfully adapted by the community organizations that were involved in coordinating the program at the local level. Their intention to continue STEP beyond extra funding shows that utilizing the local community in designing, implementing and evaluating programs promotes ownership and sustainability. PMID- 20589530 TI - SIGNR1 ligation on murine peritoneal macrophages induces IL-12 production through NFkappaB activation. AB - We have previously shown that murine resident peritoneal macrophages (PEMs) are activated in response to uptake of oligomannose-coated liposomes (OMLs), leading to production of interleukin (IL)-12. To understand the mechanism of activation of PEMs by OMLs, in the present study we investigated the role of a mannose binding C-type lectin receptor, SIGNR1, in production of proinflammatory cytokines by PEMs, in which SIGNR1 acts as a physiological receptor for OMLs. Engagement of SIGNR1 on PEMs with an anti-SIGNR1-specific rat IgM antibody, ERTR9, induced production of IL-12 and tumor necrosis factor (TNF)-alpha from PEMs, while secretion of IL-6 and IL-1beta was not detected with the same treatment. The level of phosphorylated IkappaB kinase in PEMs also increased in response to ERTR9 treatment of the cells. Treatment of PEMs with a specific nuclear factor kappa-B (NFkappaB) inhibitor, BAY11-7082, reduced ERTR9-dependent IL-12 production. Intraperitoneal treatment with BAY11-7082 also led to reduction of subsequent OML-induced IL-12 production from PEMs. These results indicate that SIGNR1-mediated intercellular signaling may induce production of cytokines such as IL-12 through NFkappaB activation. PMID- 20589531 TI - Right ventricular inefficiency in repaired tetralogy of Fallot: proof of concept for energy calculations from cardiac MRI data. AB - Repaired tetralogy of Fallot (rTOF) patients develop right ventricular (RV) dilatation and dysfunction. To prevent their demise, pulmonary valve replacement is necessary, though appropriate timing for it is challenged by a paucity of reliable diagnostic parameters. In this pilot study, we hypothesized that stroke work (SW) and energy calculations would delineate the inefficiency of RV performance in rTOF. RV SW was calculated for both an rTOF and a normal subject by utilizing RV pressure and volume measurements obtained during cardiac catheterization and MRI studies. Energy transfer rate and ratio were computed at the main pulmonary artery (PA). Compared to the normal RV, the rTOF RV had higher operating pressure, lower computed SW (0.078 J vs. 0.115 J for normal), and higher negative energy transfer at the PA (0.044 J vs. 0.002 J for normal). Furthermore, the energy transfer ratio was nearly twice as high for the normal RV (1.06) as for the rTOF RV (0.56). RV SW and energy transfer ratio delineate important operational efficiency differences in blood flow from the RV to the PA between rTOF and normal subjects. Our pilot data suggest that the rTOF RV is significantly less efficient than normal. PMID- 20589532 TI - Quantitative analysis of bulk flow in image-based hemodynamic models of the carotid bifurcation: the influence of outflow conditions as test case. AB - Although flow-driven mechanisms associated with vascular physiopathology also deal with four-dimensional phenomena such as species transport, the majority of the research on the subject focuses primarily on wall shear stress as indicator of disturbed flow. Indeed, the role that bulk flow plays in vascular physiopathology has not been thoroughly investigated, partly because of a lack of descriptors that would be able to reduce the intricacy of arterial hemodynamics. Here, an approach is proposed to investigate, in silico, the bulk flow within the carotid bifurcation. For this purpose, we coupled a three-dimensional model of carotid bifurcation with a lumped model of the downstream vasculature. For the sake of comparison, we also imposed three different fixed flow rate repartitions between the internal and external carotid arteries on the three-dimensional model. The bulk flow was characterized by applying a descriptor of helical motion, the helical flow index (HFI) to the model; the HFI has recently been shown to provide an accurate representation of complex flows. Moreover, a new metric is presented to investigate the vorticity dynamics within the bifurcation. Our results highlight the effectiveness of these metrics in the following contexts: (i) identifying and ranking emerging hemodynamic features and (ii) quantifying the influence of the outflow boundary conditions on the composition of the translational and rotational components of the fluid motion. The metrics applied herein allow for a more comprehensive analysis, which may lead to the development of an instrument to relate the bulk flow to vascular pathophysiological events that involve not only fluid-related forces, but also transport phenomena within blood. PMID- 20589533 TI - Plasma membrane integrity and survival of melanoma cells after nanosecond laser pulses. AB - Circulating tumor cells (CTCs) photoacoustic detection systems can aid clinical decision-making in the treatment of cancer. Interaction of melanin within melanoma cells with nanosecond laser pulses generates photoacoustic waves that make its detection possible. This study aims at: (1) determining melanoma cell survival after laser pulses of 6 ns at lambda = 355 and 532 nm; (2) comparing the potential enhancement in the photoacoustic signal using lambda = 355 nm in contrast with lambda = 532 nm; (3) determining the critical laser fluence at which melanin begins to leak out from melanoma cells; and (4) developing a time resolved imaging (TRI) system to study the intracellular interactions and their effect on the plasma membrane integrity. Monolayers of melanoma cells were grown on tissue culture-treated clusters and irradiated with up to 1.0 J/cm2. Surviving cells were stained with trypan blue and counted using a hemacytometer. The phosphate buffered saline absorbance was measured with a nanodrop spectrophotometer to detect melanin leakage from the melanoma cells post-laser irradiation. Photoacoustic signal magnitude was studied at both wavelengths using piezoelectric sensors. TRI with 6 ns resolution was used to image plasma membrane damage. Cell survival decreased proportionally with increasing laser fluence for both wavelengths, although the decrease is more pronounced for 355 nm radiation than for 532 nm. It was found that melanin leaks from cells equally for both wavelengths. No significant difference in photoacoustic signal was found between wavelengths. TRI showed clear damage to plasma membrane due to laser-induced bubble formation. PMID- 20589534 TI - Luteolin suppresses growth and migration of human lung cancer cells. AB - Luteolin, 3',4',5,7-tetrahydroxyflavone, has been shown to possess antioxidant, anti-inflammation and anti-cancer properties. However, its role in lung cancer remains poorly understood. Here we examined the anti-tumorigenic role of luteolin in a commonly used lung cancer cell line. Luteolin inhibited the growth of A549 cells by inducing G1 phase cell cycle arrest and apoptosis. Furthermore, stress fiber assembly and cell migration in A549 cells was markedly suppressed by luteolin. PMID- 20589535 TI - Changes in cerebral hemoglobin indices in obstructive sleep apnea syndrome with nasal continuous positive airway pressure treatment. AB - INTRODUCTION: This study examined both the relationship between the changes in the brain tissue hemoglobin indices and SpO(2) during sleep in patients with obstructive sleep apnea syndrome (OSAS) and the effect of nasal continuous positive airway pressure (CPAP) treatment on hemoglobin indices. MATERIALS AND METHODS: Polysomnographic recordings and near-infrared spectroscopy (NIRS) were performed during an afternoon nap on 15 OSAS patients before treatment and 12 healthy controls. Oxyhemoglobin (HbO), deoxyhemoglobin (HbD), and total hemoglobin (HbT) on NIRS were analyzed, and the correlation of these variables and peripheral arterial oxygen saturation (SpO(2)) were investigated in the OSAS group before nasal CPAP treatment. In nine OSAS patients, the recordings were also compared between the condition with and without using CPAP. RESULTS: HbO decreased during obstructive respiratory events while HbT and HbD showed adverse increases, and the values of these hemoglobin indices returned to the baseline values at the end of each respiratory event in the OSAS group. The fluctuations in these cerebral hemoglobin indices during sleep were significantly larger in the OSAS group than in the control group. Moreover, in the OSAS group, these changes correlated strongly with the change in SpO(2). When using CPAP, not only respiratory events but also the fluctuations in both the cerebral hemoglobin indices and SpO(2) were almost completely suppressed. CONCLUSION: Arterial oxygen desaturation is clearly related to cerebral oxygenation, and fluctuations of hemoglobin indices can be suppressed with CPAP. PMID- 20589536 TI - Religious involvement, social engagement, and subjective health status of older residents of informal neighborhoods of Nairobi. AB - Although past research has extensively documented the effects of religious involvement and social integration on the health outcomes of older people, relatively little research has examined the relationship among older Africans. In this article, we examined the effects of religious affiliation and participation as well as forms of social engagement, including social support, sociability, and community participation on self-reported health. The study used data from a sample of older men and women (50 years and above) from two informal settlements in Nairobi Kenya. Differences in religious groups were statistically significant. Frequency of religious attendance was negatively associated with health, while the number of close friends, social support, and frequency of community participation were positively and independently related to self-reported health. PMID- 20589537 TI - Facilitating ethical reflection among scientists using the ethical matrix. AB - Several studies have indicated that scientists are likely to have an outlook on both facts and values that are different to that of lay people in important ways. This is one significant reason it is currently believed that in order for scientists to exercise a reliable ethical reflection about their research it is necessary for them to engage in dialogue with other stakeholders. This paper reports on an exercise to encourage a group of scientists to reflect on ethical issues without the presence of external stakeholders. It reports on the use of a reflection process with scientists working in the area of animal disease genomics (mainly drawn from the EADGENE EC Network of Excellence). This reflection process was facilitated by using an ethical engagement framework, a modified version of the Ethical Matrix. As judged by two criteria, a qualitative assessment of the outcomes and the participants' own assessment of the process, this independent reflective exercise was deemed to be successful. The discussions demonstrated a high level of complexity and depth, with participants demonstrating a clear perception of uncertainties and the context in which their research operates. Reflection on stakeholder views and values appeared to be embedded within the discussions. The finding from this exercise seems to indicate that even without the involvement of the wider stakeholder community, valuable reflection and worthwhile discourse can be generated from ethical reflection processes involving only scienitific project partners. Hence, the previous assumption that direct stakeholder engagement is necessary for ethical reflection does not appear to hold true in all cases; however, other reasons for involving a broad group of stakeholders relating to governance and social accountability of science remain. PMID- 20589538 TI - Variation in the uric acid transporter gene SLC2A9 and its association with AAO of Parkinson's disease. AB - Based on the observed inverse association between hyperuricemia and Parkinson's disease (PD) risk, the natural antioxidant activity of uric acid has been suggested to play a protective role. SLC2A9 has been indicated as the most effective of all uric acid transporters, and SLC2A9 variants have been shown to influence circulating uric acid levels. With this study, we aimed to test the association between such SLC2A9 polymorphisms and age at onset (AAO) of PD. Variants rs733175, rs737267, rs1014290, and rs6449213 within SLC2A9 were genotyped in 664 PD individuals from three European centers. The effect of each polymorphism on AAO was estimated within each center using a linear regression model adjusted for gender and genotype at the other SNPs and assuming an additive genetic model. Results across centers were combined using inverse-variance weighted fixed-effect meta-analysis. The minor allele of rs1014290, previously shown to be associated with lower serum uric acid levels, was found to be associated with a lower AAO of PD (pooled estimate -4.56 years; 95% CI -8.13, 1.00; p=0.012). The association remained significant after adjustment for multiple comparisons and was highly consistent across centers (heterogeneity, I (2) 0%). No gender differences were observed. Our study suggests that SLC2A9 genetic variants influence age of onset of Parkinson's disease. PMID- 20589540 TI - Perianal infections: a primer for nonsurgeons. AB - The topic of perianal infections covers a broad range of illnesses that can be difficult to differentiate from each other. As a result, patients may suffer from unnecessary examinations and ineffective or delayed therapeutic interventions. This article reviews common and unusual infectious pathology and inflammatory or malignant conditions that should be considered in the differential diagnosis. Presentations of infectious pathology specific to HIV are discussed. New treatment strategies, where available, are noted. PMID- 20589541 TI - Papers presented at the 2009 closed meeting of the International Hip Society: editorial comment. PMID- 20589542 TI - A practice-based approach to group identification in nonverbal learning disorders. AB - Evidence-based practice, the rigorous conduct of clinical analysis and intervention, includes practice-based evidence. Here, practice data were the source of three "clinical portraits" used for exploratory analysis of an array of cognitive and social problems in 30 children whose neurobehavioral profiles fulfilled psychometric criteria for a nonverbal learning disability (NLD). Qualitative analysis of the children's academic and adjustment difficulties revealed patterns of dissociable deficits. These findings argue for at least three groups within the NLD construct. Identifying such subgroups is of practical importance: More precise characterization of neuropsychological competencies leads to improved interventions and better outcomes. PMID- 20589539 TI - An eight-year snapshot of geospatial cancer research (2002-2009): clinico epidemiological and methodological findings and trends. AB - Geographic information systems (GIS) offer a very rich toolbox of methods and technologies, and powerful research tools that extend far beyond the mere production of maps, making it possible to cross-link and study the complex interaction of disease data and factors originating from a wide range of disparate sources. Despite their potential indispensable role in cancer prevention and control programmes, GIS are underrepresented in specialised oncology literature. The latter has provided an impetus for the current review. The review provides an eight-year snapshot of geospatial cancer research in peer reviewed literature (2002-2009), presenting the clinico-epidemiological and methodological findings and trends in the covered corpus (93 papers). The authors concluded that understanding the relationship between location and cancer/cancer care services can play a crucial role in disease control and prevention, and in better service planning, and appropriate resource utilisation. Nevertheless, there are still barriers that hinder the wide-scale adoption of GIS and related technologies in everyday oncology practice. PMID- 20589543 TI - Implicit attributional style revisited: evidence for a state-specific "self decreasing" implicit attributional style in patients with persecutory delusions. AB - INTRODUCTION: Although evidence suggests a discrepancy between the implicit and explicit attributional style (AS) in persons with persecutory delusions, this line of research has also produced conflicting findings. Thus, the aim of this study was to explain inconsistent results in implicit AS by introducing a modified assessment of implicit AS, which offered three attributional loci (internal, personal, and situational) instead of two (internal and external) as in previous studies and by investigating the associations between implicit AS, implicit self-esteem, explicit AS, and explicit self-esteem. METHODS: Patients with acute persecutory delusions, patients with remitted persecutory delusions, and nonclinical controls were assessed in their implicit and explicit AS and implicit and explicit self-esteem. RESULTS: Deluded patients presented an implicit "self-decreasing" AS compared to remitted patients and controls: They attributed negative events more towards themselves and positive events more towards situational factors, whereas their explicit self-serving AS was comparable to controls. Patients' implicit self-decreasing AS was associated with low implicit self-esteem. In addition, compared to remitted patients and controls, deluded patients presented low explicit and normal implicit self esteem. CONCLUSIONS: The results shed light on the inconsistent findings in previous studies and indicate that persecutory delusions might be fed by implicit self-decreasing AS and an unstable self-esteem. PMID- 20589544 TI - Computational structural modelling of coronary stent deployment: a review. AB - The finite element (FE) method is a powerful investigative tool in the field of biomedical engineering, particularly in the analysis of medical devices such as coronary stents whose performance is extremely difficult to evaluate in vivo. In recent years, a number of FE studies have been carried out to simulate the deployment of coronary stents, and the results of these studies have been utilised to assess and optimise the performance of these devices. The aim of this paper is to provide a thorough review of the state-of-the-art research in this area, discussing the aims, methods and conclusions drawn from a number of significant studies. It is intended that this paper will provide a valuable reference for future research in this area. PMID- 20589545 TI - Assessment of the acrylamide intake of the Belgian population and the effect of mitigation strategies. AB - The acrylamide (AA) intake of the Belgian consumer was calculated based on AA monitoring data of the Belgian Federal Agency for the Safety of the Food Chain (FASFC) and consumption data of the Belgian food consumption survey coordinated by the Scientific Institute for Public Health (3214 participants of 15 years or older). The average AA exposure, calculated probabilistically, was 0.4 microg kg( 1) body weight (bw) day(-1) (P97.5 = 1.6 microg kg(-1) bw day(-1)), the main contributors to the average intake being chips (23%), coffee (19%), biscuits (13%), and bread (12%). Additionally, the impact of a number of AA mitigation scenarios was evaluated (German minimization concept, scenarios for mitigation from the literature, signal values), which is an important issue for public health as well as for policy-makers. Specific actions in cooperation with the food industry to reduce the AA content of foods seems to be a more efficient strategy than mere implementation of signal values. Considering that an important share of the AA intake is due to prepared meals, the catering industry as well as consumers need to be better informed on the various possibilities for keeping the AA content of meals as low as possible. PMID- 20589546 TI - Determination of furan levels in commercial samples of baby food from Brazil and preliminary risk assessment. AB - Commercial baby food samples available on the Brazilian market (n = 31) were analysed for furan content using a gas chromatography-mass spectrometry method preceded by solid-phase microextraction. A limit of detection of 0.7 microg kg( 1), a limit of quantitation of 2.4 microg kg(-1), mean recoveries varying from 80% to 107%, and coefficients of variation ranging from 5.6% to 9.4% for repeatability and from 7.4% to 12.4% for within-laboratory reproducibility were obtained during an in-house validation. The levels of furan found in the samples were from not detected to 95.5 microg kg(-1). Samples containing vegetables and meat showed higher furan levels as compared with those containing only fruits. An exposure assessment showed furan intakes up to 2.4 microg kg(-1) body weight day( 1) (99th percentile) for babies fed exclusively with commercial baby foods. Margins of exposure obtained from intakes estimated in this work indicated a potential public health concern. PMID- 20589547 TI - Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia. AB - The intake of heterocyclic amines is influenced by the amount and type of meat and fish ingested, frequency of consumption, cooking methods, cooking temperature, and duration of cooking. In this study, the dietary intake of heterocyclic amines in Malaysia and their main sources were investigated. Forty two samples of meat and fish were analysed by high-performance liquid chromatography with photodiode array detector to determine the concentration of the six predominant heterocyclic amines, namely: 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f] quinoline(MeIQ), 2-amino-3,8 dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f] quinoxaline (7,8 DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary intake data were obtained using a food-frequency questionnaire when interviewing 600 Malaysian respondents. The level of total heterocyclic amines in food samples studies ranged from not detected to 38.7 ng g(-1). The average daily intake level of heterocyclic amine was 553.7 ng per capita day(-1). The intake of PhIP was the highest, followed by MeIQx and MeIQ. The results reveal that fried and grilled chicken were the major dietary source of heterocyclic amines in Malaysia. However, the heterocyclic amine intake by the Malaysian population was lower than those reported from other regions. PMID- 20589548 TI - Dietary intake of arsenic by children and adults from Jinhu area of China. AB - The aim of this study was to estimate the dietary intake of arsenic (As) by children and adults from Jinhu area of China. A duplicate diet approach was used to collect diet samples in November and December 2007. The As content was measured by hydride generation atomic fluorescence spectrometry. The As intakes (median) for different group were: children: 0.6 microg kg(-1) bw day(-1) or 6.7 microg kg(-1) bw week(-1); adults: 0.5 microg kg (-1) bw day(-1) or 3.8 microg kg (-1) bw week(-1), none of which exceeded the provisional tolerable weekly intake (PTWI) of 15 microg kg (-1) bw week(-1) for As proposed by the World Health Organization (WHO). The median and maximum of the children group amounted to 44.7% and 125.3% of the PTWI; the values for adults were 25.3% and 118.7%, respectively. There were 3.3% of children whose weekly As intake exceeded the PTWI, and there were 6.7% of adults whose weekly As intake exceeded the PTWI. It is concluded that dietary As intake was safe for most people in Jinhu area, but the high dietary As intake for a minority of people in this area deserves attention. PMID- 20589549 TI - Aflatoxins and ochratoxin A in tea prepared from naturally contaminated powdered ginger. AB - The migration of several major mycotoxins, aflatoxins B(1) (AFB(1)), B(2), G(1), and G(2) (AFT, total of the aflatoxins) and ochratoxin A (OTA), from naturally contaminated powdered ginger to surrounding liquid (tea) was investigated. The toxins are commonly found in cereal grains and are toxic, carcinogenic and thermostable. Ginger root is widely used for digestive problems. Powdered ginger (2 g) found to contain AFT and OTA was placed in an empty heat sealable tea bag. The tea bag was heat-sealed and used to prepare tea under different conditions: temperature (50 and 100 degrees C), time (5 and 10 min) and volume (100 and 200 ml). The tea bag was placed in hot water and stirred every 1 min for 5 s during the first 5 min of steeping. After steeping, the tea bag was removed and the tea and ginger residue (in the tea bag) were analysed separately for AFT and OTA. After extraction and immunoaffinity column (IAC) clean-up, the isolated AFT and OTA were separated by reversed-phase liquid chromatography and quantified using a fluorescence detector. At 100 degrees C, approximately 30-40% of AFB(1) and AFT and 20-30% of OTA in the contaminated ginger were found in the ginger tea; the total amounts of AFT and OTA in tea varied less than 5% under the three conditions of preparation. At 50 degrees C, about 10% of OTA and AFT were found in tea. This is the first study on the migration of AFT from botanicals to tea. It is also the first to study the distribution of AFT and OTA from powdered ginger to tea and ginger residue. PMID- 20589551 TI - Spatial patterns monitoring of road traffic injuries in Karachi metropolis. AB - This article aims to assess the pattern of road traffic injuries (RTIs) and fatalities in Karachi metropolis. Assessing the pattern of RTIs in Karachi at this juncture is important for many reasons. The rapid motorisation in the recent years due to the availability of credit has significantly increased the traffic volume of the city. Since then, the roads of Karachi have continuously developed at a rapid pace. This development has come with a high human loss, because the construction of multilevel flyovers, signal-free corridors and the resulting high speed traffic ultimately increase the severity of injuries. The reasons for this high proportion are inadequate infrastructure, poor enforcement of safety regulations, high crash severity index and greater population of vulnerable road user groups (riders and pedestrians). This research is the first of its kind in the country to have a geocoded database of fatalities and injuries in a geographical information system for the entire city of Karachi. In fact, road crashes are both predictable and preventable. Developing countries should learn from the experience of highly motorised nations to avoid the high burden of RTIs by adopting road safety and prevention measures. PMID- 20589550 TI - Evaluation of fumonisin biomarkers in a cross-sectional study with two high-risk populations in China. AB - Levels of serum and urinary sphinganine (Sa) and sphingosine (So), the Sa/So ratio, and urinary-free fumonisin B(1) (FB(1)) were determined in a cross sectional study consisting of 43 adults in Huaian and 34 adults in Fusui, China. Home-produced corn had 100% contamination with FB(1). There were 93.0% (40/43) of Huaian subjects and 52.9% (18/34) of Fusui subjects with daily FB(1) intakes greater than 2 microg kg(-1) body weight, which showed a significant difference (p < 0.01). Levels of sphinganine and sphingosine and the Sa/So ratio were not correlated with levels of dietary exposure. The median level of the serum Sa/So ratio in Huaian subjects (0.41, range = 0.14-0.85) was significantly lower than that in Fusui subjects (0.78, range = 0.57-1.08) (p < 0.01). The median level of the urinary Sa/So ratio was also significantly lower in Huaian subjects (0.31, range = 0.08-1.33) than in Fusui subjects (0.57, range = 0.03-2.52) (p < 0.01). Urinary-free FB(1) was detected in 83.7% (36/43) of Huaian samples and in 82.4% (28/34) of Fusui urine samples (p > 0.05). However, the median level of urinary free FB(1) in Huaian subjects, 3.91 (range = 0.06-253.61) ng mg(-1) creatinine, was significantly higher than 0.39 (range = 0.01-3.72) ng mg(-1) creatinine found in Fusui subjects (p < 0.01). These results suggest that urinary-free FB(1) may be a potential biomarker for human fumonisin exposure, while further validation is needed in human epidemiological and intervention studies. PMID- 20589552 TI - The baby boomer effect: changing patterns of substance abuse among adults ages 55 and older. AB - Between now and 2030, the number of adults aged 65 and older in the United States will almost double, from around 37 million to more than 70 million, an increase from 12% of the U.S. population to almost 20%. It was long held that, with only a few isolated exceptions, substance abuse simply did not exist among this population. In light of the impact of the baby boom generation, this assumption may no longer be valid. The authors examined admissions of persons 55 years and older (n = 918,955) from the Treatment Episode Data Set (1998-2006). Total admissions with a primary drug problem with alcohol have remained relatively stable over this time. Admissions for problems with a primary drug other than alcohol have shown a steady and substantial increase. Clearly, data from the Treatment Episode Data Set indicate a coming wave of older addicts whose primary problem is not alcohol. The authors suspect that this wave is led primarily by the continuing emergence of the baby boomer generation. PMID- 20589553 TI - The National Family Caregiver Support Program: a multivariate examination of state-level implementation. AB - Research on caregiver support policy implementation has offered valuable insights but has not incorporated theoretical frameworks or multivariate analysis. This article describes how the communications model for intergovernmental policy implementation was used as a framework to examine predictors of successful statewide implementation of the National Family Caregiver Support Program (NFCSP). Using data from the National Center on Caregiving State of the States survey, U.S. Census, Administration on Aging, and historical records, implementation (extent of service delivery) was examined in 50 states and the District of Columbia. State-level characteristics (demographic, historical, political, and organizational) were tested for their ability to explain more or less successful implementation. Bivariate and multivariate findings suggest that historical characteristics predict the likelihood of delivering more counseling, support group, and training. States that recognize caregivers as both service recipients (through counseling and support groups) and service providers (through training) may demonstrate more effective implementation. PMID- 20589554 TI - Immigrant and non-immigrant certified nursing assistants in nursing homes: how do they differ? AB - This study analyzes the 2004 National Nursing Assistant Survey and other survey data to examine the characteristics and experiences of immigrant and non immigrant certified nursing assistants (CNAs) in nursing facilities. Descriptive results focus on differences in personal characteristics, working conditions, extrinsic rewards, work experiences, job satisfaction, and workplace discrimination. The findings indicate that immigrant CNAs are older, better educated, and somewhat more highly paid than their non-immigrant counterparts but also experience substantial levels of discrimination and language-related communication barriers at work. The paper discusses major policy issues that arise from the increase in immigrant labor in long-term care. PMID- 20589555 TI - Diffusion of the property tax work-off program for senior homeowners in Massachusetts. AB - Property tax work-off programs (TWOPs) provide senior homeowners with relief from some of their property tax obligations in exchange for services provided to local governments. These programs are offered by some county and municipal governments at their own discretion in a number of states. Through a qualitative study comparing municipalities in Massachusetts that participate in the program with similar communities that do not participate, the authors sought to learn the reasons for both participation and nonparticipation. They interviewed local officials in eight participating and six nonparticipating communities. Mohr's theory for adoption and Roger's theory for diffusion are used for the conceptual framework of the study. Local leaderships' motivation, financial or political resources and obstacles, senior homeowners' awareness, communication between communities, and perceived benefits of the program were the major factors in adoption and diffusion of TWOPs in Massachusetts. PMID- 20589556 TI - Mandatory testing of drivers on the basis of age and degenerative diseases: stakeholder opinions. AB - Concerns about the driving competence of older drivers have led to policy discussions about mandatory aged-based and disorder-based assessments. This study explored the attitudes, beliefs, and preferences of older adults, law enforcement officers, and licensing authorities toward reexamination of driving skills for persons with Alzheimer's disease (AD) and Parkinson's disease (PD) and at varying ages. With few exceptions, participants across all groups supported retesting drivers with AD. Moderate support was given for further evaluation of 90-year olds and those with PD. Least endorsement was given for reassessment of 70-year old drivers. Findings have implications for legislative changes to address drivers with AD and PD and at older ages. PMID- 20589557 TI - Parenting and temperament prior to September 11, 2001, and parenting specific to 9/11 as predictors of children's posttraumatic stress symptoms following 9/11. AB - Parenting is related to children's adjustment, but little research has examined the role of parenting in children's responses to disasters. This study describes parenting responses specific to the 9/11 terrorist attacks and examines pre-9/11 parenting, child temperament, and 9/11-specific parenting as predictors of children's posttraumatic stress (PTS) symptoms among children geographically distant from the attack locations. A community sample of children and parents (n = 137, ages 9-13 years) participating in an ongoing study were interviewed 1 month following 9/11. Parents reported engaging in a number of parenting responses following 9/11. Pre-9/11 acceptance and 9/11-specific, self-focused parental responses predicted PTS symptoms. Pre-9/11 parenting and temperament interacted to predict PTS symptoms, suggesting that parenting and temperament are important prospective predictors of children's responses to indirect exposure to disasters. PMID- 20589558 TI - Attack-related life disruption and child psychopathology in New York City public schoolchildren 6-months post-9/11. AB - In the aftermath of disasters, understanding relationships between disaster related life disruption and children's functioning is key to informing future postdisaster intervention efforts. The present study examined attack-related life disruptions and psychopathology in a representative sample (N = 8,236) of New York City public schoolchildren (Grades 4-12) surveyed 6 months after September 11, 2001. One in 5 youth reported a family member lost their job because of the attacks, and 1 in 3 reported their parents restricted their postattack travel. These forms of disruption were, in turn, associated with elevated rates of probable posttraumatic stress disorder and other anxiety disorders (and major depressive disorder in the case of restricted travel). Results indicate that adverse disaster-related experiences extend beyond traumatic exposure and include the prolonged ripple of postdisaster life disruption and economic hardship. Future postdisaster efforts must, in addition to ensuring the availability of mental health services for proximally exposed youth, maintain a focus on youth burdened by disaster-related life disruption. PMID- 20589559 TI - Variations in risk and treatment factors among adolescents engaging in different types of deliberate self-harm in an inpatient sample. AB - This study employs a framework adopted in 2008 by Jacobson, Muehlenkamp, Miller, and Turner to explore differences in risk and treatment factors in a sample of 476 adolescent inpatients grouped with relation to their involvement in deliberately self-harmful (DSH) behavior. Participants were assigned to groups indicating no DSH, nonsuicidal self-injury (NSSI) only, suicide attempts (SA) only, and NSSI + SA. Groups were compared with respect to their status on a variety of background risk factors (e.g., maltreatment, presenting psychopathology, family history) and in-treatment behaviors (e.g., critical incidents resulting from self-injurious gestures) linked to DSH. Findings generally supported the conclusions drawn by Jacobson et al. in terms of the overall severity of youth exhibiting NSSI + SA, with some important similarities observed between the NSSI-only and NSSI + SA groups. PMID- 20589560 TI - Automatic evaluations in clinically anxious and nonanxious children and adolescents. AB - Automatic evaluations of clinically anxious and nonanxious children (n = 40, aged 8-16, 18 girls) were compared using a pictorial performance-based measure of automatic affective associations. Results showed a threat-related evaluation bias in clinically anxious but not in nonanxious children. In anxious participants, automatic evaluations of anxiety-relevant stimuli were more negative than those of negative stimuli. In nonanxious participants, evaluations of negative and anxiety-relevant stimuli did not differ. Furthermore, anxious youth had stronger negative evaluations of anxiety-relevant stimuli than nonanxious children. Automatic evaluations of positive, neutral, and negative stimuli did not differ between groups. Threat-related evaluations were predictive of parent-reported, but not child-reported, anxiety. PMID- 20589561 TI - Mental disorders in five-year-old children with or without developmental delay: focus on ADHD. AB - Epidemiological studies of children and adolescents with intellectual disability have found 30 to 50% exhibiting clinically significant behavior problems. Few studies, however, have assessed young children, included a cognitively typical comparison group, assessed for specific disorders, and/or studied family correlates of diagnosis. We assessed 236 5-year-old children--95 with developmental delay (DD) and 141 with typical development--for clinical diagnoses using a structured interview. Every disorder assessed was more prevalent in the DD group. The percent of children meeting criteria for Attention Deficit Hyperactivity Disorder (ADHD) most highly differentiated the two groups (ratio = 3.21:1). There was high stability from externalizing behavior problems at age 3 to ADHD diagnoses at age 5 in both groups. In regression analyses, parenting stress at child age 3 related to later ADHD diagnosis in both groups and maternal scaffolding (sensitive teaching) also predicted ADHD in the DD group. PMID- 20589562 TI - The Pittsburgh Girls Study: overview and initial findings. AB - The Pittsburgh Girls Study is a longitudinal, community-based study of 2,451 girls who were initially recruited when they were between the ages of 5 and 8 years. The primary aim of the study was testing developmental models of conduct disorder, major depressive disorder, and their co-occurrence in girls. In the current article, we summarize the published findings from the past 5 years of the PGS and place those results in the context of what it known to date about developmental psychopathology in girls. Key results suggest that DSM-IV mental disorders tend to have an insidious onset often beginning with subsyndromal symptom manifestation, and that there appear to be shared and unique developmental precursors to disorder in subgroups of girls based on race and poverty. PMID- 20589564 TI - Perceived physical appearance mediates the rumination and bulimic symptom link in adolescent girls. AB - The prospective relationship between initial rumination and subsequent bulimic symptoms, and vice versa, was examined, and possible mediators were tested in a community sample of 191 adolescent girls (M age = 14.5) at 3 different assessment time points. Path analyses indicated that Time 1 rumination predicted Time 3 bulimic symptoms, and vice versa. Physical appearance competence (but not social competence) mediated both relationships. The results suggest that specific cognitive mechanisms, such as rumination, may play an etiological role in the development of bulimic symptoms. This may be especially true for adolescent girls who exhibit low competence beliefs about their physical appearance. PMID- 20589563 TI - The development of effortful control in children born preterm. AB - This prospective longitudinal study examined emerging effortful control skills at 24- and 36-months postterm in 172 children born preterm (<36 weeks gestation). Infant (neonatal health risks), family (sociodemographic risks), and maternal risk factors (depressive symptoms, anger expressions during play interactions) were assessed at six time points across 3 years. In addition, children's emerging effortful control skills, cognitive development, and mother-reported behavior and attention problems were assessed at 24 and 36 months. Analyses documented links between effortful control skills, cognitive skills, and concurrent attention problems in children born preterm. The study also found that preterm children's effortful control skills improved over time. In addition, neonatal health risks, family sociodemographic risks, and angry parenting interactions were associated with less optimal effortful control skills. PMID- 20589565 TI - Associations between first use of substances and change in internalizing symptoms among girls: differences by symptom trajectory and substance use type. AB - This study examined how girls' initial use of alcohol, cigarettes, and marijuana related to changes in depressive, generalized anxiety, and social anxiety symptoms, and whether these changes varied based on which internalizing symptom trajectories the girls were on. Data came from the Pittsburgh Girls Study, a community-based study of girls assessed at ages 5 to 8 and followed for 6 years. Growth mixture modeling was used to identify trajectory groups. The results indicated that for girls on a "high depressive symptom" trajectory, initial use of marijuana was related to further increases in depressive symptoms. Initial uses of alcohol and cigarettes were associated with overall increases in depressive symptoms, and the initial use of cigarettes was associated with an overall increase in generalized anxiety symptoms. Initial use of all substances was related to change in social anxiety, but the direction of change varied by trajectory group and substance. Links between initial use and internalizing symptoms depended on the type of substance, type of internalizing symptom, and trajectory group. PMID- 20589567 TI - Who benefits and how does it work? Moderators and mediators of outcome in an effectiveness trial of a parenting intervention. AB - We examined mediators and moderators of change in conduct problems, in a multiagency randomized trial of the Incredible Years parenting program. Preschoolers (n = 153) at risk for conduct problems were randomly assigned to intervention (n = 104) and wait-list (n = 49) groups. Boys and younger children, and those with more depressed mothers, tended to show greater improvement in conduct problems post-intervention. Other risk factors (i.e., teen or single parenthood, very low income, high initial levels of problem behavior) showed no predictive effects, implying intervention was at least as successful at helping the most disadvantaged families, compared to more advantaged. Mediator analyses found change in positive parenting skill predicted change in conduct problems. PMID- 20589566 TI - Treating depression and oppositional behavior in adolescents. AB - Adolescents with depression and high levels of oppositionality often are particularly difficult to treat. Few studies, however, have examined treatment outcomes among youth with both externalizing and internalizing problems. This study examines the effect of fluoxetine, cognitive behavior therapy (CBT), the combination of fluoxetine and CBT, and placebo on co-occurring oppositionality within a sample of depressed adolescents. All treatments resulted in decreased oppositionality at 12 weeks. Adolescents receiving fluoxetine, either alone or in combination with CBT, experienced greater reductions in oppositionality than adolescents not receiving antidepressant medication. These results suggest that treatments designed to alleviate depression can reduce oppositionality among youth with a primary diagnosis of depression. PMID- 20589568 TI - Effects of maternal stimulant medication on observed parenting in mother-child dyads with attention-deficit/hyperactivity disorder. AB - This pilot study of 23 mothers with attention-deficit/hyperactivity disorder (ADHD) and their offspring with ADHD examined the effects of maternal stimulant medication on observed interactions. Parent-child interactions were observed using a structured protocol before and after mothers underwent a 5-week, double blind stimulant titration. Despite dramatic effects of medication on adult ADHD symptoms, this small pilot and open label laboratory-based study did not identify maternal stimulant effects on observed parenting or child behavior. Given the documented impairments in parenting displayed by adults with ADHD, behavioral parenting interventions may be needed in conjunction with medication for mothers with ADHD to optimize family outcomes. PMID- 20589569 TI - Screening and predicting posttraumatic stress and depression in children following single-incident trauma. AB - Three screening methods to predict posttraumatic stress disorder (PTSD) and depression symptoms in children following single-incident trauma were tested. Children and adolescents (N = 90; aged 7-17 years) were assessed within 4 weeks of an injury that led to hospital treatment and followed up 3 and 6 months later. Screening methods were adapted from existing instruments and examined (a) an Australian version of the Screening Tool for Predictors of PTSD (STEPP-AUS), (b) an abbreviated measure of initial PTSD severity, and (c) an abbreviated measure of initial maladaptive trauma-specific beliefs. The STEPP-AUS correctly identified 89% of the children who developed PTSD at 6-month follow-up and the 69% of children who were non-PTSD. Predictive performance of the others instruments was generally poor, and no instrument consistently predicted subclinical levels of depression. PMID- 20589570 TI - Co-rumination and lifetime history of depressive disorders in children. AB - Co-rumination, the social process of frequently discussing and rehashing problems with peers, is hypothesized to increase risk for depression, particularly for girls. Although there is growing evidence for a relation between co-rumination and depressive symptoms in youth, it remains unclear whether these results generalize to diagnosable episodes of depression. Using a retrospective behavioral high-risk design with 81 children aged 9 to 14 years, we tested the hypothesis that children currently exhibiting high levels of co-rumination would be more likely to have a history of depressive diagnoses than children with low levels of co-rumination. The results supported this hypothesis. In addition, the link between co-rumination and history of depressive diagnoses was maintained even when we excluded children with current diagnoses and statistically controlled for children's current depressive symptoms, suggesting that the relation is not due simply to current levels of depression. PMID- 20589571 TI - Reinvestigation of the synthesis of 1-deazauridine. AB - A thorough study for the synthesis of 1-deazauridine is described. 3-Bromo-2,6 dimethoxy-5-(beta-D-ribofuranosyl)pyridine, a synthetic precursor for 1 deazauridine, was prepared in seven steps from 2,6-dimethoxypyridine and d-ribose via the ribonolactone approach. Subsequent demethylation was unsuccessful but led to presumable anomerization and isomerization. The effort concluded that the synthesis of 1-deazauridine remained unachieved. PMID- 20589572 TI - Synthesis of novel 6-azapyrimidine acyclic nucleoside analogues and antiviral evaluation. AB - Acyclic nucleosides have been of considerable interest since the approval of aciclovir by the FDA to be used as an antiviral agent in the 1990s. The acyclic moieties and the bases used in the experiment were either available commercially or synthesized using literature methods. Vorbruggen coupling method was utilized involving reaction of persilylated heterocyclic bases with the appropriate acyclic moiety in the presence of a Lewis acid catalyst. A series of novel 6 azapyrimidine acyclic oxosugar nucleosides was successfully synthesized with a promising yield (more than 50%). An efficient method of protection and deprotection was also investigated. PMID- 20589573 TI - Highly efficient and facile synthesis of 5-azido-2'-deoxyuridine. AB - Previously reported syntheses of the photoaffinity label 5-azido-2'-deoxyuridine are rather inefficient and involve the tedious preparation of a 5-nitro intermediate. To overcome these inconveniences, we have developed a new approach from the commercially available 5-bromo-2'-deoxyuridine nucleoside. Our synthetic route makes use of a benzylamination reduction sequence. Using this strategy, the 5-azido-2'-deoxyuridine photolabel is prepared in three steps and quantitative yields. PMID- 20589574 TI - cDNA, genomic sequence cloning, and overexpression of EIF1 from the giant panda (Ailuropoda Melanoleuca) and the black bear (Ursus Thibetanus Mupinensis). AB - Eukaryotic initiation factor (eIF) EIF1 is a universally conserved translation factor that is involved in translation initiation site selection. The cDNA and the genomic sequences of EIF1 were cloned successfully from the giant panda (Ailuropoda melanoleuca) and the black bear (Ursus thibetanus mupinensis) using reverse transcription polymerase chain reaction (RT-PCR) technology and touchdown polymerase chain reaction, respectively. The cDNAs of the EIF1 cloned from the giant panda and the black bear are 418 bp in size, containing an open reading frame (ORF) of 342 bp encoding 113 amino acids. The length of the genomic sequence of the giant panda is 1909 bp, which contains four exons and three introns. The length of the genomic sequence of the black bear is 1897 bp, which also contains four exons and three introns. Sequence alignment indicates a high degree of homology to those of Homo sapiens, Mus musculus, Rattus norvegicus, and Bos Taurus at both amino acid and DNA levels. Topology prediction shows there are one N-glycosylation site, two Casein kinase II phosphorylation sites, and a Amidation site in the EIF1 protein of the giant panda and black bear. In addition, there is a protein kinase C phosphorylation site in EIF1 of the giant panda. The giant panda and the black bear EIF1 genes were overexpressed in E. coli BL21. The results indicated that the both EIF1 fusion proteins with the N terminally His-tagged form gave rise to the accumulation of two expected 19 kDa polypeptide. The expression products obtained could be used to purify the proteins and study their function further. PMID- 20589575 TI - Stereoselective nucleoside deuteration for NMR studies of DNA. AB - A procedure has been elaborated for stereoselective deuterium substitution of one of the diastereotopic 5'-protons in 2'-deoxynucleotides. The synthetic scheme uses the reduction of the 5-oxosugar derivative with deuterated Alpine-Borane. The resulting deuterosugar is converted into pyrimidine nucleosides and incorporated into DNA using standard protocols. Comparison of two-dimensional NMR spectra of the fully protonated and partially deuterated duplexes allowed us to assign diastereotopic 5' protons, increasing the number of experimental restraints used for structure determination. PMID- 20589576 TI - The effect of testosterone upon the urate reabsorptive transport system in mouse kidney. AB - It is hypothesized that hyperuricemia in males is caused by androgen-induced urate reabsorptive transport system in the kidney. The expression of urate transporter 1 (Urat1), sodium-coupled monocarboxylate transporter 1 (Smct1) and glucose transporter 9 (Glut9) were investigated in orchiectomized mice with or without testosterone replacement. Testosterone enhanced mRNA and protein levels of Smct1 while those of Glut9 were attenuated. Although the mRNA level of Urat1 was enhanced by testosterone, the corresponding levels of Urat1 protein remained unaffected. Thus, the induction of Smct1 by testosterone is a candidate mechanism underlying hyperuricemia in males. PMID- 20589577 TI - A note on: the joint effect of maternal malnutrition and cold weather on neonatal mortality in nineteenth-century Venice: an assessment of the hypothermia hypothesis, Population Studies 63(3): 233-251 by Renzo Derosas. PMID- 20589580 TI - Simon-like and functional affordance effects with tools: the effects of object perceptual discrimination and object action state. AB - In the present study two separate stimulus-response compatibility effects (functional affordance and Simon-like effects) were investigated with centrally presented pictures of an object tool (a torch) characterized by a structural separation between the graspable portion and the goal-directed portion. In Experiment 1, participants were required to decide whether the torch was red or blue, while in Experiment 2 they were required to decide whether the torch was upright or inverted. Our results showed that with the same stimulus two types of compatibility effect emerged: one based on the direction signalled by the goal directed portion of the tool (a Simon-like effect as observed in Experiment 1), and the other based on the actions associated with an object (a functional affordance effect as observed in Experiment 2). Both effects emerged independently of the person's intention to act on the stimulus, but depended on the stimulus properties that were processed in order to perform the task. PMID- 20589582 TI - [Single-port transumbilical endoscopic cholecystectomy: a new standard?]. AB - BACKGROUND AND OBJECTIVE: Single-port transumbilical laparoscopic cholecystectomy (SPTLC) may become a standard procedure in the surgical treatment of acute and chronic gallbladder diseases. The initial experience with this new technique is reported. METHODS: 186 patients underwent laparoscopic single-port laparoscopic cholecystectomy between September 2008 and February 2010 at the Vivantes Klinikum Am Urban, Berlin, Germany. All these operations were performed with conventional straight laparascopic instruments using a single-port system. RESULTS: Conversion to a three-port technique or open procedure became necessary in four patients after failure to perform the single-port method. The average age of the 120 women (64%) and 66 men (36%) was 45 (range 15-88 years) years. The ASA grade (American Society of Anesthesiologists) averaged 2 (range, 1-3) and the BMI 28.5 (range 17 49). Mean operative time was 63 min (range, 28-17 min). 48 patients (26%) had histopathological evidence of acute cholecystitis. During a mean follow-up period of 39 weeks (range 1-78 weeks), 11 patients (6%) developed complications related to the surgery, five of these patients (3%) requiring a subsequent re-operation. CONCLUSIONS: Single-port transumbilical laparoscopic cholecystectomy for acute and chronic gallbladder disease is a feasible approach for routine cholecystectomy. After a short learning curve the operation time and rate of complications are comparable to standard multi-port laparoscopic cholecystectomy. A limitation of the procedure are very obese patients and multiple previously performed abdominal operations. PMID- 20589583 TI - [Factitious recurrent septicemia and gastrointestinal corrosive burns]. AB - HISTORY AND ADMISSION FINDINGS: A 39-year-old woman was admitted for the treatment of recurrent septicemia, corrosive esophageal and gastric mucosal injury, and bloody stools. INVESTIGATIONS: A search of her hospital room provided evidence of a self-inflicted disorder. Bacteremia with typical fecal flora had been caused by self-injected intravenous inoculation of stool and the esophageal ulcers by swallowed vinegar. TREATMENT AND COURSE: The patient was initially treated with meropenem. After initial clinical and psychological stabilization the patient refused further psychiatric or psychosomatic treatment. CONCLUSION: Fluctuating or bizarre symptoms and unusual diagnostic findings may indicate self inflicted disorders, in which the symptoms of illness are caused by the afflicted person him/herself. PMID- 20589584 TI - [Amiodarone-induced liver dysfunctions]. AB - Amiodarone, a diiodinated benzofuran derivative, is widely used for treating ventricular and supraventricular tachyarrhythmias. Amiodarone is highly lipophilic and accumulation in the liver can be 500 times higher than serum amiodarone levels. Due to a long half-life and the lipophilic properties, the stored drug is capable of damaging the liver long after the drug has been stopped. Serious liver damage can lead to acute liver failure, cirrhosis and the need for liver transplantation. In this article we describe amiodarone-induced liver dysfunction and the diagnostic and therapeutic challenges in patients on amiodarone. PMID- 20589585 TI - [84-year old patient with vertigo and dyspnoea after pacemaker implantation. Exit block caused by fracture of the ventricular pacemaker lead]. PMID- 20589587 TI - [Tick-borne encephalitis virus in humans and ticks in Northeastern Germany]. AB - Tick-borne encephalitis (TBE) was known to have occurred in humans in the area of Mecklenburg-Western Pomerania in Germany, until 1985. Between 1992 and 2004 more than 16,000 ticks were tested and found to be negative for TBE virus in that area of Germany, wich was therefore thought to be free of TBE. But after 19 years three autochthonous cases of human TBE-infections were identified between 2004 and 2006. We subsequently collected ticks from the three areas where the infection had been acquired and tested them for the presence of TBE-virus RNA with a nested reverse transcription polymerase chain reaction (RT-PCR). Since there is evidence that a blood-meal leads to an increase of FSME-RNA in ticks, we tested both, unfed ticks and ticks after a blood-meal. Three unfed and one fed nymph from the area around Lake Woblitz and one unfed and one fed nymph from Thiessow were positive for TBE-virus RNA. A total of six of 250 (2.4%) ticks tested positive for TBE-virus. The emerging of human TBE infections in three regions in Mecklenburg-Western Pomerania shows that the activity of natural TBE virus foci does not cease even after decades, or that TBE-infected ticks could have recolonized these regions. PMID- 20589586 TI - [Mucocutaneous candidiasis]. AB - Infection with the yeast candida is a quite common disease. Its occurrence might be harmless, however, Candida infections often present with an underlying systemic disease. Thus, candidiasis in some cases can be considered as an indicator for e.g. diabetes mellitus or immune deficiency (i.e. HIV or leukaemia). Of note, we have to distinguish the colonisation and the infection with Candida because only the presence of the yeast together with clinical symptoms is an indication for treatment. The latter has to be adapted according to age, localisation and potentially underlying systemic disease. A special form of Candidiasis constitutes the chronic mucocutaneous candidiasis which can occur in line with hereditary immune deficiencies or also isolated. In the present review we discuss the current status of diagnostic and therapy of mucocutaneous candidiasis as well as the (patho-) immunologic background of yeast infections using the example of a special case of chronic mucocutaneous candidiasis. PMID- 20589588 TI - A mechanomyographic fatigue threshold test for cycling. AB - The purposes of this study were twofold: 1) to derive the mechanomyographic mean power frequency fatigue threshold (MMG MPFFT) for submaximal cycle ergometry; and 2) to compare the power outputs associated to the MMG MPFFT to other neuromuscular and gas exchange fatigue thresholds. 9 adults (5 men and 4 women; mean+/-SD age=23.7+/-3.7 years; body weight=66.3+/-8.2 kg) performed an incremental cycle ergometry test to exhaustion while expired gas samples, electromyographic (EMG), and MMG signals were measured from the vastus lateralis muscle. The non-significant correlations (r=0.17 to 0.66; p>0.05) among the physical working capacity at the fatigue threshold (PWCFT), MMG MPFFT, and gas exchange threshold (GET) suggested that different physiological mechanisms may underlie these 3 fatigue thresholds. A significant correlation (r=0.83) for the MPFFT vs. respiratory compensation point (RCP) suggested that these fatigue thresholds may be mediated by a common physiological mechanism. In addition, the significantly lower mean values found for the PWCFT (mean+/-SD=163+/-43 W), MMG MPFFT (132+/-33 W), and GET (144+/-28 W) than MPFFT (196+/-53 W) and RCP (202+/ 41 W) suggested that these gas exchange and neuromuscular fatigue thresholds may demarcate different exercise intensity domains. PMID- 20589589 TI - Effect of leg length on ROM, VJ and leg dexterity in dance. AB - We investigated the associations between leg length and specific ballet movements in different skill groups. Volunteers were from an undergraduate dance programme (n=18), a pre-professional school (n=43) and from an elite classical ballet company (n=45). Individual data were collected for anthropometry, vertical jump, leg dexterity, and leg active and passive ROM. ANCOVA identified both main effects as significant with regard to vertical jump (gender P<0.001 and skill P=0.017); leg length was also identified as a significant covariate (P=0.023). Analysis of leg dexterity identified no significant effects with gender, skill or leg length. Active and passive range of motion noted gender (P=0.001) and skill (P<0.001) differences. Leg length was found to be negatively associated with both active and passive ROM (P=0.002). In conclusion, the present data highlight the diverse and conflicting effects of leg length on fundamental ballet skills. The longer legs that benefit vertical jump have a negative influence on range of motion and leg dexterity except for highly skilled dancers, who through skill, seem to have overcome the effects of some of these dichotomies. PMID- 20589590 TI - Vibration effects on static balance and strength. AB - The purpose of this study was to investigate the effects of a vibration training protocol and a conventional strength training program consisting of similar exercises on knee extensors and flexors strength and postural sway in middle-aged women. 38 women were randomly assigned into a Vibration Group (n=12, static and dynamic exercises on a vibration plate, frequency: 15-25 Hz, amplitude: 2-12.8 cm), a Strength Group (n=16, same exercises without vibration) and a Control Group (n=10). Both experimental groups trained for 12 weeks (3 sessions/w). Static balance was assessed in 3 tasks of increasing difficulty: Normal Quiet Stance, Sharpened Tandem, and One-Legged Stance. Postural sway was evaluated using the Centre of Pressure variations in the Anterior/Posterior and Medio/Lateral direction. Eccentric and concentric strength of knee extensors and flexors was recorded using a Cybex dynamometer. After vibration training, postural sway significantly decreased in both directions for the vibration group in all tasks (p<0.05), whereas no significant differences were observed for the other groups. Isokinetic strength significantly (p<0.05) increased for both experimental groups at selected angular velocities. It was concluded that side alternating vibration could have beneficial effects on static balance control for middle-aged women. Gains in isokinetic strength were quite similar for both experimental groups. PMID- 20589591 TI - Effects of intermittent hypoxia on running economy. AB - We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy (RE). 11 male and female middle-distance runners were randomly assigned to the intermittent hypoxia group (IHG) or to the control group (CG). All athletes trained for a 13-wk period starting at pre-season until the competition season. The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia (15-11% FiO2). RE, haematological parameters and body composition were determined at low altitude (600 m) at baseline, after the 5 (th), the 8 (th) and the 13 (th) week of training. RE, determined by the relative oxygen consumption during submaximal running, (-2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg, P<0.05) and total running time (+1.0+/-0.9 vs. +0.4+/-0.5 min, P<0.05) changed significantly between the IHG and CG only during the first 5-wk period. Haematological and cardiorespiratory changes indicate that the improved RE was associated with decreased cardiorespiratory costs and greater reliance on carbohydrate. Intermittent hypoxia did not affect RE during the second 5-wk period. These findings suggest that the effects of intermittent hypoxia on RE strongly depend on the training phase. PMID- 20589592 TI - Relationship between ventilatory thresholds and systolic blood pressure variability. AB - During exercise, an increase in respiratory rate amplifies the blood pressure oscillations. This phenomenon is usually intensified when exercise rate exceeds the ventilatory thresholds (VTs). The present study examined whether VTs assessment was possible from systolic blood pressure variability (SBPV) analysis to give blood pressure ventilatory thresholds (BPVTs). Blood pressure, ECG, and Ventilatory equivalents (VE/VO2, VE/VCO2) were collected from 15 well-trained subjects during an incremental exhaustive test performed on a cycloergometer. The "Short-Time Fourier Transform" was applied to SBP series to compute the instantaneous high frequency SBPV power (HF-SBPV). BPVTs were determined in all but 3 subjects. For the 12 remaining subjects, visual examination of ventilatory equivalents and HF-SBPV power revealed 2 thresholds for both methods. There was no difference between the first (VT1 235+/-60 vs. BPVT1 226+/-55 W, p=0.063) and second (VT2 293+/-67 vs. BPVT2 301+/-66 W, p=0.063) thresholds. However, BPVT1 was slightly underestimated compared to VT1 (9.9+/-15.4 W) given lower limit of agreement (LOA) at -19.9 W and higher at 40.4 W. BPVT2 was over-estimated compared to VT2 (-8.8+/-11.2 W) given lower LOA at -30.9 W and higher at 13.4 W. Thus, BPVTs determination appears useful in conditioning programs with sedentary or pathological subjects but probably not with trained subjects. PMID- 20589593 TI - Regulation of muscle genes by moderate exercise. AB - Moderate-intensity exercise at the lactate threshold (LT) is considered to be a safe and effective training regimen for improving metabolic syndrome. The aim of the current study was to investigate the effects of moderate exercise performed at the LT on skeletal muscle gene expression. 6 healthy men participated in cycle ergometer training at LT, 60 min/d, 5 d/wk for 12 wks. Muscle samples were collected after 5 d of training, and then 2 d after training at wks 6 and 12. Quantitative real-time PCR analysis revealed that the expression of peroxisome proliferator activated receptor co-activated 1alpha was significantly increased at 1 h after the training session on day 5. Moreover, using serial analysis gene expression, we found that moderate training for 6 and 12 wks simultaneously induced the expression of a number of metabolic genes involved in the TCA cycle, beta-oxidation, and electron transport. Furthermore, several genes encoding antioxidant enzymes and contractile apparatus were induced. The expression levels of 233 novel transcripts were also altered in response to moderate exercise. Thus, moderate training at the LT is a sufficient stimulus to induce the expression of numerous genes implicated in the development of metabolic syndrome, transcripts involved in the contractile apparatus, and novel transcripts. PMID- 20589594 TI - Endoscopic retrograde cholangiopancreatography using a single-balloon enteroscope in patients with altered Roux-en-Y anatomy. AB - BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is challenging to perform in patients with postsurgical gastrointestinal anatomy. We assessed the diagnostic and therapeutic success rates using single-balloon enteroscopy in patients with Roux-en-Y anastomosis. PATIENTS AND METHODS: Patients who underwent single-balloon ERCP between April 2008 and February 2010 were retrospectively identified using a computerized endoscopy database. Diagnostic success was defined as successful duct cannulation or securing the diagnosis, and therapeutic success was defined as the ability to successfully carry out endoscopic therapy. Complications of ERCP were defined according to standard criteria. RESULTS: A total of 50 patients (34-male, mean age 57 years, range 19 - 85 years) with Roux-en-Y anastomosis underwent ERCP using a single balloon enteroscope on 56 occasions. Indications for ERCP were cholestasis, acute cholangitis, recurrent primary sclerosing cholangitis with strictures, and choledocholithiasis. Overall diagnostic success was achieved in 39 / 56 cases (70 %). Therapeutic success was achieved in 21/23 cases (91 %). In 16 cases therapeutic intervention was not required. Therapeutic interventions included balloon dilation of strictures (n = 14), retrieval of retained biliopancreatic stents (n = 5), biliary stone extraction (n = 2), insertion of biliopancreatic stents (n = 4), and biliary and pancreatic sphincterotomy (n = 5). No major complications occurred. Importantly, in 22 / 56 procedures (39 %) a prior attempt at ERCP failed using conventional colonoscopes; single-balloon ERCP was successful in 15 / 22 (68 %) of these cases. CONCLUSIONS: Single-balloon ERCP is feasible in patients with complex postsurgical Roux-en-Y anastomosis, allows diagnostic evaluation and therapeutic intervention in patients with pancreaticobiliary disease, and is a useful salvage technique in the majority of patients in whom ERCP using colonoscopies has failed. PMID- 20589595 TI - Routine pathological evaluation of neuroma specimens: is there a rationale? AB - The routine pathological analysis of therapeutically resected traumatic or postoperative neuroma specimens to confirm diagnosis and rule out occult malignancy remains a controversial issue. Some experts advocate histological analysis of all specimens, and others rely on institutional policy. A retrospective chart review of all patients who underwent excision of clinically diagnosed neuroma over a 6-year period at one institution by a single surgeon was initiated. The correlation of preoperative diagnoses with histological analysis and cost of analyzing specimens individually and over the 6-year period was calculated. Of 515 neuromas resected, 100 were sent for pathological review. Every submitted specimen was histologically confirmed to be a traumatic neuroma, and none of the specimens harbored occult malignancy. Ultimately, no treatment plan was altered after final histology was confirmed. The cost to analyze each specimen (Current Procedural Terminology code 88305) was $495, expressed in U.S. dollars. If every specimen was analyzed, a total cost of $254,925 would have be incurred over the 6-year period. Routine pathological analysis of clinically and intraoperatively confirmed neuromas must be questioned in terms of standard of care requirements given its failure to aid in treatment plans as well as its significant cost to health care systems. PMID- 20589596 TI - Trials assessing parmacotherapeutic management of aggression in psychiatric patients: comparability with clinical practice. AB - INTRODUCTION: In a previous review of randomized controlled trials (RCTs) on the pharmacotherapeutic management of aggression, it was shown that there is only weak evidence of effectiveness. In the present study we aim to determine comparability of patients included in these RCTs and patients of psychiatric long stay wards. METHODS: Exclusion criteria that were used in at least 20% of the RCTs were applied to a sample of aggressive inpatients from clinical practice, in order to find what proportion of these patients would be eligible to participate in the reviewed, high quality RCTs. RESULTS: Only 30% of aggressive psychiatric patients as seen in clinical practice would be eligible to participate in a typical randomized controlled trial based on the most frequently applied exclusion criteria. DISCUSSION: The low comparability of patients included in RCTs with those seen in clinical practice may decrease the generalizability of the findings form RCTs to clinical practice. PMID- 20589597 TI - Factors associated with response in depressed elderly outpatients treated with escitalopram in a naturalistic setting in Germany. AB - BACKGROUND: An open, multi-centre study was designed to address the effectiveness and tolerability profile of treatment with escitalopram under naturalistic conditions, in elderly outpatients (above 65 years of age) with depression. PATIENTS AND METHODS: A total of 2 050 patients completed 8 weeks of treatment with escitalopram. Rating scales included a short version of the Montgomery Asberg Depression Rating Scale (svMADRS), the Clinical Global Impression - Severity scale (CGI-S), and the Clinical Global Impression -Improvement scale (CGI-I) for the assessment of various clinical parameters. RESULTS: Most patients improved in their general state of health and showed a decrease in the severity of their depression. The majority (82.7%) of patients received initially 10 mg/day escitalopram. The mean svMADRS total score decreased from 31.9+/-7.9 at baseline to 14.2+/-8.5 at week 8. On completion, 63.9% of the patients were responders (> or =50% decrease of svMADRS total score from baseline) and 48.6% were remitters (svMADRS total score < or =12 at week 8). Statistically significantly more patients aged between 66 and 75 years responded to treatment and achieved remission than those aged >75 years. Logistic regression, using stepwise backward elimination, was used to model response to treatment. Statistically significant positive factors were having a current episode < or =1 month and duration of illness < or =1 year. Significant negative factors were being male, being older than 75 years, and having need of further psychotropic medication. Compared to patients diagnosed with unspecified dementia with other symptoms being predominantly depressive (F03, according to ICD-10), the response to escitalopram was significantly better for patients with depressive episodes (F32) or recurrent depressive episodes (F33), but significantly worse for patients with affective disorder (F31 or F34). The differences versus affective disorders were significant, while those for depressive episodes and recurrent depressive episodes vs. affective disorders were not significant. CONCLUSION: This observational study corroborates the effectiveness and tolerability of escitalopram treatment for elderly patients in a naturalistic treatment setting. PMID- 20589598 TI - Long-term efficacy and tolerability of clozapine combined with ziprasidone or risperidone. AB - INTRODUCTION: Treatment resistance in schizophrenia often leads to add-on of atypical antipsychotics to clozapine. METHODS: In a randomized trial, we recently obtained evidence for comparable efficacy and differential side effects of clozapine in combination with ziprasidone (CZ, N=12) versus risperidone (CR, N=12). Here, we present the open-label, long-term evaluations of these patients after 26 and 52 weeks. RESULTS: Sustained improvements of psychopathology as assessed by PANSS (positive and negative syndrome scale), SANS (scale for the assessment of negative symptoms), and HAMD (Hamilton depression scale) were documented in both subsamples being treated according to protocol, while dropouts reduced the study sample after 26 (CZ: reduced by -4; CR: -2) and 52 weeks (CZ: 0; CR: -5). We observed a slight increase of akathisia in the CZ group whereas general clozapine-associated side effects improved. DISCUSSION: The combinations of clozapine with ziprasidone or risperidone exhibit long-term efficacy, but the level of evidence is limited. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary. PMID- 20589599 TI - Information-seeking practices of senior medical students: the impact of an evidence-based medicine training programme. AB - CONTEXT: The practice of Evidence-based Medicine (EBM) involves physicians regularly accessing and appraising clinical information. Few prior studies have assessed the information-seeking behaviours of medical undergraduates. At the International Medical University (IMU), Malaysia, senior medical students receive clinically-integrated EBM training to facilitate their future practice of EBM. OBJECTIVES: We assessed whether EBM training in the final six months of medical training changes our students' information-seeking practices and their confidence in understanding and appraising clinical evidence. METHODS: Between September 2005 and February 2006, self-administered questionnaires were distributed to 65 senior medical students at the beginning and again at the end of their clerkship training during which there was a clinically-integrated EBM curriculum. The questionnaires covered the topics of their preferred sources of clinical information, online search frequencies, estimated time to retrieve an abstract, and their understanding and confidence in their critical appraisal skills. FINDINGS: Sixty-four (98%) students completed the initial survey and 63 (97%) completed the follow-up survey. The majority indicated that they preferred to first consult another individual (colleagues, lecturers, hospital staff) for their clinical queries (60.9% in the initial survey and 61.9% in the follow-up survey), with no change in their overall preference following the EBM curriculum six months later (p=0.144). There were significant increases in search activities following the curriculum, for example, students who searched PubMed or Medline for more than three times per week increased from 9.7% to 31.7% (p < 0.001). Students reported that they more often accessed single journals than databases. Despite significant improvements in students' reported understanding of journals and their confidence in critical appraisal (p < 0.001), there was no improvement in reported search speed, with 48.4% in the initial survey and 49.2% in the follow-up survey reporting to take 30 minutes or less to trace an abstract of interest (p=0.979). CONCLUSIONS: Our EBM training, offered within a supportive curriculum, increased our students' confidence and activity related to EBM, but failed to change students' reported information-seeking behaviours. Other factors influencing medical students' information-seeking practice need to be explored. PMID- 20589600 TI - The practice and tradition of bonesetting. AB - CONTEXT: Traditional bonesetting is an art that in the face of urbanization, lack of public attention and lack of modern facilities has survived more than 3,000 years. This article explores the role of bonesetters in the developing world, their successes and failures and possible utilization of their services as part of the healthcare system of a country. METHODS: Articles depicting working or techniques of bonesetters or those related to training and education issues of traditional bonesetters, especially in developing countries, were reviewed. The current scenario of healthcare delivery and medical education along with existing socioeconomic conditions prevailing in India were analyzed with generalization of findings to the healthcare delivery systems of other developing countries. FINDINGS: Bonesetting has its strengths and weaknesses. With current socioeconomic conditions and the types of health needs prevailing in developing countries, it would be difficult to abolish traditional bonesetting. These providers have widespread community acceptance and support. Complications can be minimized and practice potentially improved with training and education. CONCLUSIONS: Pending infrastructure and socioeconomic development, it appears that traditional bonesetters will remain providers of healthcare. Their methodology utilizes regional resources and is commonly believed to be cheaper and effective. Although the deficiencies of traditional bonesetters have been shown, with adequate training in the basics of orthopaedic care, they can be utilized to provide useful health services at the primary care level. PMID- 20589601 TI - Global health is "the new pink.". PMID- 20589602 TI - Further confirmation of the psychometric properties of responses to the psychological medicine inventory -student version. AB - CONTEXT: The Psychological Medicine Inventory (PMI) was first developed to measure physicians' reported interest level, confidence and perceived ability to address the psychological aspects of patient care. A student version of this scale has since been proposed (PMI-S). OBJECTIVE: To further examine the psychometric properties of responses to this student version and to confirm a 2 factor response structure. METHODS: A total of 213 first-year medical students at Ben-Gurion University of the Negev participated in this study. They completed the PMI-S (translated into Hebrew) and a socio-demographic questionnaire. The viability of the 2-factor structure of PMI-S responses was assessed using confirmatory factor analysis (CFA). FINDINGS: Consistent with the original English language version, CFA supported a 2-factor solution (i.e., psychological abilities and psychological sensitivity). All goodness-of-fit indices were found to be within ideal parameters. DISCUSSION AND CONCLUSIONS: Results of this study suggest that the PMI-S can be used to assess psychosocial competence and abilities of medical students and to evaluate the effectiveness of psycho educational programs aimed at improving their psychosocial abilities. PMID- 20589603 TI - Group dynamics and social interaction in a South Asian online learning forum for faculty development of medical teachers. AB - BACKGROUND: Group dynamics of online medical faculty development programs have not been analyzed and reported in literature. Knowledge of the types of content of posted messages will help to understand group dynamics and promote participation in an asynchronous learning environment. This paper assesses group dynamics and social interactivity in an online learning environment for medical teachers in the South Asian context. METHODS: Participants of a medical education fellowship program conducted by the Foundation for Advancement of International Medical Education and Research (FAIMER) Regional Institute at Christian Medical College, Ludhiana (CMCL) in India interact on a listserv called the Mentoring Learning Web (ML-Web). Monthly topics for online discussion are chosen by fellows through a standard tool called "multi-voting". Fellows volunteer to moderate sessions and direct the pace of the discussion. We analyzed the content and process of the discussion of one particular month. The emails were categorized as those that reflected cognitive presence (dealing with construction and exploration of knowledge), teacher presence (dealing with instructional material and learning resources), and social presence, or were administrative in nature. Social emails were further classified as: affective, cohesive and interactive. RESULTS: Social emails constituted one-third of the total emails. Another one quarter of the emails dealt with sharing of resources and teacher presence, while cognitive emails comprised 36.2% of the total. More than half of the social emails were affective, while a little less than one-third were cohesive. CONCLUSION: Social posts are an inevitable part of online learning. These posts promote bonding between learners and contribute to better interaction and collaboration in online learning. Moderators should be aware of their presence and use them as tools to promote interactivity. PMID- 20589604 TI - Validation of the Greek translation of the Dundee Ready Education Environment Measure (DREEM). AB - CONTEXT: The educational environment makes an important contribution to student learning. The DREEM questionnaire is a validated tool assessing the environment. OBJECTIVES: To translate and validate the DREEM into Greek. METHODS: Forward translations from English were produced by three independent Greek translators and then back translations by five independent bilingual translators. The Greek DREEM.v0 that was produced was administered to 831 undergraduate students from six Greek medical schools. Cronbach's alpha and test-retest correlation were used to evaluate reliability and factor analysis was used to assess validity. Questions that increased alpha if deleted and/or sorted unexpectedly in factor analysis were further checked through two focus groups. FINDINGS: Questionnaires were returned by 487 respondents (59%), who were representative of all surveyed students by gender but not by year of study or medical school. The instrument's overall alpha was 0.90, and for the learning, teachers, academic, atmosphere and social subscales the alphas were 0.79 (expected 0.69), 0.78 (0.67), 0.69 (0.60), 0.68 (0.69), 0.48 (0.57), respectively. In a subset of the whole sample, test and retest alphas were both 0.90, and mean item scores highly correlated (p<0.001). Factor analysis produced meaningful subscales but not always matching the original ones. Focus group evaluation revealed possible misunderstanding for questions 17, 25, 29 and 38, which were revised in the DREEM.Gr.v1. The group mean overall scale score was 107.7 (SD 20.2), with significant differences across medical schools (p<0.001). CONCLUSION: Alphas and test-retest correlation suggest the Greek translated and validated DREEM scale is a reliable tool for assessing the medical education environment and for informing policy. Factor analysis and focus group input suggest it is a valid tool. Reasonable school differences suggest the instrument's sensitivity. PMID- 20589605 TI - Outcomes from the trial implementation of a multidisciplinary online learning program in rural mental health emergency care. AB - INTRODUCTION: Emergency Departments (EDs) are often the first point of contact for people with acute mental health problems. The impact of the Mental Health Emergency Care (MHEC) online learning program on the knowledge and skills development of clinicians and support staff was evaluated, and options for sustainable implementation of the program were proposed. METHODS: Participants were recruited from the four rural health services and the rural areas of one metropolitan health service in New South Wales, Australia. The MHEC course was conducted online over 24 weeks and comprised four sequential modules, each based on a clinical scenario that demonstrated a typical, acute mental health presentation to a general hospital ED. The course was designed to model collaborative practice in mental health emergency care. RESULTS: Participants were surveyed before and after completing the MHEC course. Statistically significant improvements were detected in participant confidence in managing key mental health problems, perceived self-efficacy in dealing with challenging, aggressive behaviours and confidence in key online learning skills. Participants also reported very positive experiences in relation to the course content and structure, instructor support, multidisciplinary discussion and feedback, and improvements in their knowledge and skills about emergency mental healthcare. CONCLUSIONS: This study provides evidence for the effectiveness and acceptability of an online educational program in developing the capacity of front-line staff to respond effectively to people who present to EDs with acute mental health problems. The positive outcomes and evaluations of the MHEC course provide support for the deployment of online learning programs that address mental health emergency care. PMID- 20589606 TI - Stress and coping strategies among Arab medical students: towards a research agenda. AB - BACKGROUND: Research conducted in the past ten years in the area of stress and coping among Arab medical students has identified some important issues, but other significant aspects have not yet been explored. OBJECTIVES: To provide a systematic review of studies reporting on stress, anxiety and coping among Arab medical students and to identify implications for future research. METHODS: PubMed was searched to identify peer-reviewed English-language studies published between January 1998 and October 2009 reporting on stress and coping among undergraduate Arab medical students. Search strategy used combinations of the terms: Arab medical student, stress, PBL, psychological distress, depression, anxiety and coping strategies. Demographic information on respondents, instruments used, prevalence data and statistically significant associations were abstracted. RESULTS: The search identified 8 articles that met the specified inclusion criteria. Within the limited range of Arab medical students studied, studies suggest these students have a high prevalence of perceived stress, depression and anxiety, with levels of perceived psychological stress as high as those reported in the international literature for medical students of other regions of the world. Limited data were available regarding coping strategies, the impact of stress on academic performance and attrition among Arab students. No data were available regarding the impact of problem-based learning on stress and coping. CONCLUSIONS: The existing literature confirms that stress, depression and anxiety are common among Arab medical students, as for students elsewhere. Little is known about the contribution of different curricula approaches to perceived stress and what coping strategies institutions and students apply to help alleviate stress. Large, prospective, multicentre, multi-method studies are needed to identify personal and curricula features that influence stress, depression, anxiety and coping strategies among Arab students. PMID- 20589607 TI - An evaluation of ROME Camp: forgotten innovation in medical education. AB - BACKGROUND AND OBJECTIVES: Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sewagram, India's first rural medical institute, has been implementing its community-based public health teaching with the aim of building a physician workforce for the rural poor. For the past four decades, the MGIMS has organized and run the Re-orientation of Medical Education (ROME) camp for final year medical undergraduates at one of the rural centres of the department of Community Medicine. The objectives of the present study were to learn students' perceptions of the value and effectiveness of various components of the ROME camp and learn the factors they perceive facilitate and inhibit learning. METHODS: A mixed method research design of quantitative (survey) and qualitative (force field analysis) methods was used. The study participants were all 61 of the final year medical undergraduates participating in the ROME camp in 2008. The quantitative data was analyzed using SPSS software package and summative content analysis of the qualitative data was undertaken. RESULTS: Students were generally very positive about all aspects of the camp and its component parts. The greatest consensus (88.9%, on a 0 to 100% scale) was for the contribution to student learning of the visit to the Primary health centre and Sub-centre, as offering direct exposure and interaction with the village-level service providers. There was poorer consensus for students' involvement with the field-based clinics, as this was felt by some not to contribute significantly to their understanding of socio-economic and environmental factors related to cases (78.8%) and their ability to diagnose health problems in resource poor settings (76.5%). The major strength of the camp was felt to be its exposure visits and hands-on experiences in surveys and interaction with village-level health care providers. Students reported poor interactions with teachers in some educational sessions, including the field-based clinics and classes on theories of national health programs. CONCLUSIONS: The curriculum of the ROME camp was generally well regarded by students, but based on their views it should emphasize interactive theory sessions. The ROME scheme can be revitalized in all medical colleges as it is an effective practical approach for teaching public health principles and practice to medical students. PMID- 20589608 TI - Innovations in medical internship: benchmarking and application within the King Saud bin Abdulaziz University for Health Sciences. AB - INTRODUCTION: While the medical internship (MI) has evolved in some countries into competency-based training with innovative tools for assessment and feedback, the traditional MI is still the norm in many countries. AIM: To describe recent advances in the MI in several countries, to discuss the current MI situation in Saudi Arabia as an example of a country that applies a traditional MI, and to present a Framework for Medical Interns' Competencies (FMIC) implemented within the King Saud bin Abdulaziz University for Health Sciences (KSAU-HS). METHODS: Common electronic databases were searched for the years 1990 to 2008 under keywords related to medical internship education. Information on curricula designed for medical interns or junior doctors in selected countries was obtained by searching relevant websites. At the KSAU-HS, the FMIC was created by first building the case for the urgent need for revising the MI and adapting international approaches to the KSA's needs, followed by dialogue among faculty and leaders, planning, coordination and execution of the framework. RESULTS: Two trends were identified in the recent evolution of the MI. In North America, the first postgraduate year now serves the traditional purpose of the MI. Australia and the United Kingdom have embedded the MI within junior doctor training. These innovative curricula have in common a focus on the domains of medical knowledge, clinical practice, professionalism and communication skills. The FMIC applies innovative principles during the MI years customized to the local medical education setting. CONCLUSION: The evolution in medical education and healthcare systems worldwide has necessitated innovations in the MI. The FMIC is a model whereby innovative curriculum was introduced to enhance the outcomes of the MI in a country that has applied a traditional MI. PMID- 20589609 TI - Implementing an interfaculty series of courses on interprofessional collaboration in prelicensure health science curriculums. AB - INTRODUCTION: Interprofessional collaborative practices are increasingly recognized as an effective way to deal with complex health problems. However, health sciences students continue to be trained in specialized programs and have little occasion for learning in interdisciplinary contexts. PROGRAM DEVELOPMENT: The project's purpose was to develop content and an educational design for new prelicensure interfaculty courses on interprofessional collaboration in patient and family-centered care which embedded interprofessional education principles where participants learn with, from and about each other. IMPLEMENTATION: Intensive training was part of a 45-hour program, offered each semester, which was divided into three 15-hour courses given on weekends, to enhance accessibility. EVALUATION: A total of 215 students completed questionnaires following the courses, to assess their satisfaction with the educational content. Pre/post measures assessed perception of skills acquisition and perceived benefits of interprofessional collaboration training. Results showed a significant increase from the students' point of view in the knowledge and benefits to be gained from interprofessional collaboration training. CONCLUSION: The implementation of an interfaculty training curriculum on interprofessional collaborative practice is challenging in many ways, though it offers a true opportunity to prepare future health human resources for contemporary practice requirements. PMID- 20589610 TI - In the News! An opinion: Use of humanities in health professions education. PMID- 20589611 TI - Reforming a health care workforce. PMID- 20589612 TI - Co-editors' notes 23:1. PMID- 20589613 TI - Correct targeting of proinsulin in protein storage vacuoles of transgenic soybean seeds. AB - Soybean plants are promising bioreactors for the expression of biochemically complex proteins that cannot be produced in a safe and/or economically viable way in microorganisms, eukaryotic culture cells or secreted by transgenic animal glands. Soybeans present many desirable agronomic characteristics for high scale protein production, such as high productivity, short reproductive cycle, photoperiod sensitivity, and natural organs destined for protein accumulation in the seeds. The significant similarities between plant and human cells in terms of protein synthesis processes, folding, assembly, and post-translational processing are important for efficient accumulation of recombinant proteins. We obtained two transgenic lines using biolystics, incorporating the human proinsulin gene under control of the monocot tissue-specific promoter from sorghum gamma-kafirin seed storage protein gene and the alpha-coixin cotyledonary vacuolar signal peptide from Coix lacryma-jobi (Poaceae). Transgenic plants expressed the proinsulin gene and accumulated the polypeptide in mature seeds. Protein targeting to cotyledonary protein storage vacuoles was successfully achieved and confirmed with immunocytochemistry assays. The combination of different regulatory sequences was apparently responsible for high stability in protein accumulation, since human proinsulin was detected after seven years under room temperature storage conditions. PMID- 20589614 TI - No relationship found between -1438A/G polymorphism of the serotonin 2A receptor gene (rs6311) and major depression susceptibility in a northeastern Thai population. AB - Several lines of evidence suggest a molecular role of -1438A/G single nucleotide polymorphism in the 5-HTR2A gene promoter (rs6311) in regulating the expression of this gene, making rs6311 polymorphism a promising candidate for an association study. We looked for a possible association between rs6311 polymorphism and major depressive disorder (MDD) in a northeastern Thai population. We included 180 patients with MDD and 183 unrelated healthy controls in our study. Genotyping was performed using PCR-RFLP. We found no significant differences between the two groups with regard to both genotype distributions (chi(2) = 1.32, d.f. = 2, P = 0.516) and allele frequencies (chi(2) = 0.01, d.f. = 1, P = 0.913, odds ratio = 0.96, 95% confidence interval = 0.67-1.39). Therefore, this single nucleotide polymorphism appears not to be involved in the etiology of MDD. PMID- 20589615 TI - ABCB1 gene expression in peripheral blood mononuclear cells in healthy Thai males and females. AB - We compared the expression of the ABCB1 gene in healthy male and female Thai subjects; this gene encodes the P-glycoprotein transporter in peripheral blood mononuclear cells (PBMCs). We also identified the most suitable housekeeping genes for normalization of ABCB1 expression levels in PBMCs. PBMCs from 30 females and 26 males were isolated. Total RNA was extracted, followed by reverse transcription (100 ng total RNA per sample). The internal normalization controls were actin-beta, beta-2M and GAPDH. Real-time quantitative PCR was then performed to determine the expression levels of the ABCB1 gene. The expression levels were found to be 1.5- to 2.5-fold higher in males, depending on the endogenous control used for normalization. Actin-beta was the most stable control gene and could be used as a single endogenous control for normalization of ABCB1 expression levels in PBMCs. However, more than one endogenous control genes are recommended for normalization of gene expression. We conclude that the expression levels of ABCB1 in PBMCs is influenced by gender; this helps, in part, explain the gender difference in pharmacokinetics and pharmacodynamics of drugs that are P glycoprotein substrates. ABCB1 gene expression profiles need to be carefully interpreted with regards to the endogenous control genes that are involved. PMID- 20589616 TI - Identification and characterization of conserved microRNAs and their target genes in wheat (Triticum aestivum). AB - MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression by translational repression or transcript degradation. A large number of miRNAs have been identified from model plant species; however, the character of conserved miRNAs is poorly understood. We studied 42 miRNA families that are conserved within the plant kingdom, using the miRBase database. Some conserved miRNA families were found to be preferentially expressed in dicots relative to monocots, especially miR403, miR472 and miR479. Using an improved homology search based approach and the conserved miRNAs as the query set, 34 conserved miRNAs and the miR482 family were identified in wheat. Forty-six wheat mRNAs were predicted as their putative target genes. Most conserved wheat miRNAs were found to retain homologous target interactions and have analogous molecular functions. The miR172 displayed a wheat-specific function and was found to have an additional target interaction with succinyl-CoA ligase. We concluded that although miRNAs are conserved, the expression and function of some have drifted during long periods of plant evolution. PMID- 20589617 TI - C677T polymorphism of the methylenetetrahydrofolate reductase gene does not affect folic acid, vitamin B12, and homocysteine serum levels in Turkish children with neural tube defects. AB - Association between neural tube defects (NTDs) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was suspected, because the MTHFR gene codes for a key enzyme in folate metabolism. Its deficiency usually leads to significant reductions in plasma concentrations of folate, vitamin B(12) and methionine, whereas homocysteine levels are increased. We examined folate, vitamin B(12) and homocysteine serum concentrations and polymorphism of the C677T MTHFR gene in Turkish children with neural tube defects. Thirty-three children with NTDs, 26 mothers and 48 healthy individuals were studied. C677T MTHFR polymorphism was determined by melting curve analyses (LightCycler). The levels of folate, vitamin B(12) and homocysteine serum concentrations in NTDs were evaluated and compared, along with information concerning alleles of the MTHFR gene. C677T allele frequencies in NTD children and their mothers were similar to those found in controls. Serum folate and vitamin B(12) concentrations were significantly higher in NTD children than that of controls. Serum homocysteine concentrations were not significantly higher in NTD children and mothers. We concluded that C677T MTHFR gene polymorphism does not affect folic acid, vitamin B(12) and homocysteine metabolism in Turkish children with NTDs. C677T polymorphism of the MTHFR gene cannot be regarded as a major risk factor for NTDs in Turkish children. PMID- 20589618 TI - Complete mitochondrial genome of Cabot's tragopan, Tragopan caboti (Galliformes: Phasianidae). AB - Cabot's tragopan, Tragopan caboti, is a globally threatened pheasant endemic to southeast China. The complete mitochondrial genome of Cabot's tragopan was sequenced. The circular genome contains 16,727 bp, encoding a standard set of 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes, plus the putative control region, a structure very similar to that of other Galliformes. As found in other vertebrates, most of these genes code on the H strand, except for the NADH dehydrogenase subunit 6 (nad6) and eight tRNA genes (Gln, Ala, Asn, Cys, Tyr, Ser(UCN), Pro, Glu). All protein-coding genes initiated with ATG, except for cox1, which began with GTG, and had a strong skew of C vs G (GC skew = -0.29 to -0.73). One extra 'C' nucleotide was found in the NADH dehydrogenase subunit 3 (nad3). All the tRNA gene sequences have the potential to fold into typical cloverleaf secondary structures. Conserved sequences in three domains were identified within the control region (D-loop). These results provide basic information for phylogenetic analyses among Galliform birds, and especially Tragopan species. PMID- 20589619 TI - Interpersonal contribution to outcome: The relation of interpersonal distress and symptomatic improvement as a result of psychotherapy. AB - The study utilized a 32-item brief measure of interpersonal problems (IIP) to examine interpersonal distress in relation to symptomology and treatment outcome as assessed by the Outcome Questionnaire-45 (OQ-45). The study included a community sample of 210 individuals receiving psychotherapy at a mental health training facility. A number of significant correlations were found between interpersonal distresses with symptomology. The highest correlations were found between levels of general interpersonal distress and symptoms relating to psychiatric and social distress at the onset of therapy; in general the IIP did not differentiate between symptomology types. The study failed to replicate previous research indicating a relation between facets of interpersonal problems with treatment outcome. PMID- 20589620 TI - Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate. AB - The FIP1L1-PDGFRA fusion gene is the most frequent genetic aberration in myeloid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. Affected patients in adult populations are very sensitive to imatinib therapy. Pediatric cases are rare and so far only one case of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting treatment. PMID- 20589621 TI - Acquired hemophilia in pediatrics: a systematic review. AB - Acquired hemophilia A is a rare but potentially life-threatening hemorrhagic disorder caused by the development of autoantibodies directed mostly against coagulation factor VIII. Acquired hemophilia is frequently associated with several underlying conditions such as malignancy, autoimmune disorders, drug reactions, and pregnancy, although the pathogenesis remains undetermined (idiopathic) in up to 50% of reported cases. The disorder occurs most commonly in the elderly and only rarely affects pediatric patients, who might however experience severe, and sometimes life-threatening, hemorrhage. The maternal transplacental transfer of the autoantibody to the neonate occurs very rarely and also in this circumstance it may be associated with clinically significant bleeding. The management of acute bleeding and the inhibitor eradication are the mainstay of the treatment. The outcome in pediatric patients seems more favorable than in adults because the inhibitors usually resolve more quickly and in a higher rate of patients. The epidemiology, diagnosis, clinical course, and management of this hemorrhagic disorder in children will be addressed in this systematic review. PMID- 20589622 TI - Defining and managing career challenges for mid-career and senior stage pediatric hematologist/oncologists. AB - A workshop at the 2008 ASPHO Annual Meeting functioned as the first step in a systematic needs assessment of the particular challenges to satisfaction and success in the middle and senior phases of career development for pediatric hematologist/oncologists (PHOs). The 61 ASPHO members who attended were randomly distributed to small discussion groups based on self-identified career stage. Groups completed challenge forms for each issue identified as pertinent to their own stage of professional development. A total of 71 forms with useable data were generated by the groups. The largest number of challenges described (26) clustered around themes of Work-Life Balance followed by Transition and Succession (18), Management and Finances (15), and Keeping up to Date (13). Mid career groups were more likely to identify Work-Life Balance challenges while senior stage groups were more likely to articulate Succession and Management challenges. The article describes the demographics of the workshop participants, summarizes the content of challenge themes and the associated suggestions for management. It is hoped that this effort will assist educational and career planning efforts by individuals, institutions, and ASPHO as a professional society. PMID- 20589623 TI - A high circulating copy number of HHV-6 due to chromosomal integration in a child with acute lymphoblastic leukemia. AB - We report a case of a 3.5-year-old female with a very high copy number of human herpesvirus 6 (HHV-6) detected by PCR in blood during acute lymphoblastic leukemia induction therapy. The patient was unsuccessfully treated with antiviral drugs. HHV-6 genome was shown to be constitutively integrated into chromosome 22q tel, likely to be inherited from the mother who was found to carry high HHV-6 copy number. This case highlights the importance of excluding HHV-6 chromosomal integration before diagnosing HHV-6 infection or reactivation in immunocompromised patients. PMID- 20589624 TI - An unusual case of acute myeloid leukemia: late isolated testicular relapse followed by isolated central nervous system relapse. AB - Testicular relapse of acute myeloid leukemia without bone marrow involvement is a rare event. We describe a case of an 18-year-old male who had an isolated testicular relapse 86 months (7.2 years) from original diagnosis. He was treated with surgery only, without adjuvant therapy. The patient then developed central nervous system involvement 9 months later. Fluorescence in situ hybridization and immunohistochemistry were used to establish the diagnosis of a relapse rather than a new leukemic process. He was treated with intrathecal chemotherapy and systemic reinduction, followed by a stem cell transplant. This patient had a 7.2 year period between original diagnosis and the testicular relapse of acute myeloid leukemia. PMID- 20589625 TI - Young age at diagnosis is a risk factor for negative late socio-economic effects after acute lymphoblastic leukemia in childhood. AB - BACKGROUND: The increasing number of survivors after childhood cancer requires characterization of the late complications of these diseases and their treatment. We examined a large number of possible socio-economic late effects following treatment for acute lymphoblastic leukemia (ALL) in order to identify factors leading to a poor outcome. PROCEDURE: All individuals who had been diagnosed with ALL and who were alive in January 2007 (n = 213; men = 107) were identified from a database of all patients with cancer before the age of 18 in Southern Sweden from 1970 to 1999. For each subject, 50 matched controls were identified from the Swedish Population Register. Information on marital status, children, education, employment, income, and support from the community was obtained from Statistics Sweden. RESULTS: At the ages of 25 and 30, survivors of ALL had attained a lower level of education than controls. At the age of 30, they were less often employed (70% vs. 82%, P = 0.019), less often married (19% vs. 32%, P = 0.019), and had children to a lesser extent (31% vs. 47%, P = 0.011) than controls. We identified young age at diagnosis as a risk factor for adverse outcome in the majority of the socio-economic variables studied, apart from the known risk of cranial irradiation treatment. Furthermore, female survivors had a greater risk of achieving a lower level of education than both male survivors and controls. CONCLUSIONS: Young age at diagnosis, as well as treatment with cranial irradiation, is a risk factor for socio-economic late effects after treatment for ALL in childhood. PMID- 20589626 TI - PHF6 mutations in T-lineage acute lymphoblastic leukemia. PMID- 20589627 TI - Judgement required. PMID- 20589628 TI - Chemotherapy and interferon-alpha treatment of Erdheim-Chester disease. AB - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis of an unknown origin. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized. Interferon-alpha (IFN) has been reported to be effective in the management of ECD. We report here on an uncommon case with ECD in a 17-year-old female who had multiple lesions in the whole body and she was treated with chemotherapy and IFN. She has remained disease-free for 2 years after the completion of treatment. PMID- 20589629 TI - Species specificity of the complement inhibitor compstatin investigated by all atom molecular dynamics simulations. AB - The development of compounds to regulate the activation of the complement system in non-primate species is of profound interest because it can provide models for human diseases. The peptide compstatin inhibits protein C3 in primate mammals and is a potential therapeutic agent against unregulated activation of complement in humans but is inactive against nonprimate species. Here, we elucidate this species specificity of compstatin by molecular dynamics simulations of complexes between the most potent natural compstatin analog and human or rat C3. The results are compared against an experimental conformation of the human complex, determined recently by X-ray diffraction at 2.4-A resolution. The human complex simulations provide information on the relative contributions to stability of specific C3 and compstatin residues. In the rat simulations, the protein undergoes reproducible conformational changes, which eliminate or weaken specific interactions and reduce the complex stability. The simulation insights can be used to design improved compstatin-based inhibitors for human C3 and active inhibitors against lower mammals. PMID- 20589631 TI - Comparing the folding free-energy landscapes of Abeta42 variants with different aggregation properties. AB - The properties of the amyloid-beta peptide that lead to aggregation associated with Alzheimer's disease are not fully understood. This study aims at identifying conformational differences among four variants of full-length Abeta42 that are known to display very different aggregation properties. By extensive all-atom Monte Carlo simulations, we find that a variety of beta-sheet structures with distinct turns are readily accessible for full-length Abeta42. In the simulations, wild type (WT) Abeta42 preferentially populates two major classes of conformations, either extended with high beta-sheet content or more compact with lower beta-sheet content. The three mutations studied alter the balance between these classes. Strong mutational effects are observed in a region centered at residues 23-26, where WT Abeta42 tends to form a turn. The aggregation accelerating E22G mutation associated with early onset of Alzheimer's disease makes this turn region conformationally more diverse, whereas the aggregation decelerating F20E mutation has the reverse effect, and the E22G/I31E mutation reduces the turn population. Comparing results for the four Abeta42 variants, we identify specific conformational properties of residues 23-26 that might play a key role in aggregation. PMID- 20589632 TI - Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction. AB - A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction. PMID- 20589630 TI - On the pH-optimum of activity and stability of proteins. AB - Biological macromolecules evolved to perform their function in specific cellular environment (subcellular compartments or tissues); therefore, they should be adapted to the biophysical characteristics of the corresponding environment, one of them being the characteristic pH. Many macromolecular properties are pH dependent, such as activity and stability. However, only activity is biologically important, while stability may not be crucial for the corresponding reaction. Here, we show that the pH-optimum of activity (the pH of maximal activity) is correlated with the pH-optimum of stability (the pH of maximal stability) on a set of 310 proteins with available experimental data. We speculate that such a correlation is needed to allow the corresponding macromolecules to tolerate small pH fluctuations that are inevitable with cellular function. Our findings rationalize the efforts of correlating the pH of maximal stability and the characteristic pH of subcellular compartments, as only pH of activity is subject of evolutionary pressure. In addition, our analysis confirmed the previous observation that pH-optimum of activity and stability are not correlated with the isoelectric point, pI, or with the optimal temperature. PMID- 20589633 TI - Consistent refinement of submitted models at CASP using a knowledge-based potential. AB - Protein structure refinement is an important but unsolved problem; it must be solved if we are to predict biological function that is very sensitive to structural details. Specifically, critical assessment of techniques for protein structure prediction (CASP) shows that the accuracy of predictions in the comparative modeling category is often worse than that of the template on which the homology model is based. Here we describe a refinement protocol that is able to consistently refine submitted predictions for all categories at CASP7. The protocol uses direct energy minimization of the knowledge-based potential of mean force that is based on the interaction statistics of 167 atom types (Summa and Levitt, Proc Natl Acad Sci USA 2007; 104:3177-3182). Our protocol is thus computationally very efficient; it only takes a few minutes of CPU time to run typical protein models (300 residues). We observe an average structural improvement of 1% in GDT_TS, for predictions that have low and medium homology to known PDB structures (Global Distance Test score or GDT_TS between 50 and 80%). We also observe a marked improvement in the stereochemistry of the models. The level of improvement varies amongst the various participants at CASP, but we see large improvements (>10% increase in GDT_TS) even for models predicted by the best performing groups at CASP7. In addition, our protocol consistently improved the best predicted models in the refinement category at CASP7 and CASP8. These improvements in structure and stereochemistry prove the usefulness of our computationally inexpensive, powerful and automatic refinement protocol. PMID- 20589634 TI - Exploring the role of the phospholipid ligand in endothelial protein C receptor: a molecular dynamics study. AB - Endothelial protein C receptor (EPCR) is a CD1-like transmembrane glycoprotein with important regulatory roles in protein C (PC) pathway, enhancing PC's anticoagulant, anti-inflammatory, and antiapoptotic activities. Similarly to homologous CD1d, EPCR binds a phospholipid [phosphatidylethanolamine (PTY)] in a groove corresponding to the antigen-presenting site, although it is not clear if lipid exchange can occur in EPCR as in CD1d. The presence of PTY seems essential for PC gamma-carboxyglutamic acid (Gla) domain binding. However, the lipid-free form of the EPCR has not been characterized. We have investigated the structural role of PTY on EPCR, by multiple molecular dynamics (MD) simulations of ligand bound and unbound forms of the protein. Structural changes, subsequent to ligand removal, led to identification of two stable and folded ligand-free conformations. Compared with the bound form, unbound structures showed a narrowing of the A' pocket and a high flexibility of the helices around it, in agreement with CD1d simulation. Thus, a lipid exchange with a mechanism similar to CD1d is proposed. In addition, unbound conformations presented a reduced interaction surface for Gla domain, confirming the role of PTY in establishing the proper EPCR conformation for the interaction with its partner protein. Single MD simulations were also obtained for 29 mutant models with predicted structural stability and impaired binding ability. Ligand affinity calculations, based on linear interaction energy method, showed that substitution-induced conformational changes affecting helices around the A' pocket were associated to a reduced binding affinity. Mutants responsible for this effect may represent useful reagents for experimental tests. PMID- 20589635 TI - Similarity of cytochrome c oxidases in different organisms. AB - Most of biological oxygen reduction is catalyzed by the heme-copper oxygen reductases. These enzymes are redox-driven proton pumps that take part in generating the proton gradient in both prokaryotes and mitochondria that drives synthesis of ATP. The enzymes have been divided into three evolutionarily-related groups: the A-, B-, and C-families. Recent comparative studies suggest that all oxygen reductases perform the same chemistry for oxygen reduction and comprise the same essential elements of the proton pumping mechanism, such as the proton loading and kinetic gating sites, which, however, appear to be different in different families. All species of the A-family, however, demonstrate remarkable similarity of the central processing unit of the enzyme, as revealed by their recent crystal structures. Here we demonstrate that cytochrome c oxidases (CcO) of such diverse organisms as a mammal (bovine heart mitochondrial CcO), photosynthetic bacteria (Rhodobacter sphaeroides CcO), and soil bacteria (Paracoccus denitrificans CcO) are not only structurally similar, but almost identical in microscopic electrostatics and thermodynamics properties of their key amino-acids. By using pK(a) calculations of some of the key residues of the catalytic site, D- and K- proton input, and putative proton output channels of these three different enzymes, we demonstrate that the microscopic properties of key residues are almost identical, which strongly suggests the same mechanism in these species. The quantitative precision with which the microscopic physical properties of these enzymes have remained constant despite different evolutionary routes undertaken is striking. PMID- 20589636 TI - Traditional laboratory measures of cardiovascular risk in hereditary spherocytosis. AB - BACKGROUND: Individuals who have undergone splenectomy may be at an increased risk of arterial and venous thrombosis. We sought to determine if splenectomy affects surrogate laboratory measures of cardiovascular risk in persons with hereditary spherocytosis (HS). PROCEDURE: We conducted a prospective cross sectional study of 21 children and 36 adults with HS. Fasting blood samples were collected for complete blood count and plasma lipid panel, homocysteine, lipoprotein (a), C-reactive protein, and fibrinogen. The variables were compared between the groups with and without prior splenectomy by Mann-Whitney tests. RESULTS: Subjects with prior splenectomy had higher hemoglobin, white blood cell and platelet counts and lower reticulocyte counts and total serum bilirubin concentrations (P < 0.001). Subjects not having had splenectomy had lower than normal levels of total and LDL-cholesterol (LDL-C). Total and LDL-C values were significantly higher, as were fibrinogen and homocysteine concentrations, in the post-splenectomy subjects than in individuals with intact spleen. CONCLUSION: Various lipid levels and other measures of cardiovascular risk are affected by splenectomy in persons with HS. Further investigations are indicated to more clearly define the balance of the potential benefits of hemolysis and anemia versus the deleterious effects of splenectomy in HS. PMID- 20589637 TI - A palliative prognostic score for terminally ill children and adolescents with cancer. AB - BACKGROUND: The loss of a child is considered the hardest moment in a parent's life. Studies addressing length of survival under pediatric palliative care are rare. The aim of this study was to improve a survival prediction model for children in palliative care, as accurate information positively impacts parent and child preparation for palliative care. PROCEDURE: Sixty-five children referred to a pediatric palliative care team were followed from August 2003 until December 2006. Variables investigated (also included in previous studies) were: diagnosis, home care provider, presence of anemia, and performance status score given by the home care provider. Clinical variables such as symptom number were also used to test the score's ability to predict survival. RESULTS: The length of survival prognostic score was validated using the above variables. The number of symptoms at transition to palliative care does not improve the score's predictive ability. The sum of the single scores gives an overall score for each patient, dividing the population into three groups by probability of 60-day survival: Group A 80.0%, Group B 38.0%, and Group C 28.5% (P < 0.001). CONCLUSION: A pediatric palliative care score based on easily accessible variables is statistically significant in multivariate analysis. Factors that increase accuracy of life expectancy prediction enable adequate information to be given to patients and families, contributing to therapeutic decision-making issues. PMID- 20589638 TI - Prolonged 14-day continuous infusion of high-dose ifosfamide with an external portable pump: feasibility and efficacy in refractory pediatric sarcoma. AB - BACKGROUND: Ifosfamide is currently used to treat pediatric sarcomas and increasing its dosage may be associated with a better response rate. Prolonged continuous infusion seems an attractive administration modality. METHODS: Ifosfamide 14 g/m(2) (with mesna 14 g/m(2)) was administered through an ambulatory portable pump over 14 days as a continuous infusion, starting every 3 weeks, in 14 patients with relapsing sarcomas. No growth factors were given. RESULTS: Acute grade 3 hematological toxicity was observed in only 13/66 cycles and red cell transfusions were given in two patients. Hematuria and dysuria occurred in three cases. The response rate was: five partial responses, five stable disease. The median time to progression was 3 months (range: 2-19 months). The best response rate was seen for synovial sarcoma and Ewing sarcoma. CONCLUSION: Prolonged 14-day continuous infusion of high-dose ifosfamide is well tolerated. Potentially interesting preliminary responses in pediatric patients already treated with ifosfamide are reported. PMID- 20589639 TI - Juvenile xanthogranuloma with hematological dysfunction treated with 2CDA-AraC. AB - Juvenile xanthogranuloma was diagnosed in two infants aged 8 and 2 months with skin lesions, hepatosplenomegaly, and pancytopenia. Disease control was not achieved with first-line vinblastine-steroid-VP16 combination therapy. Two courses of 2-chlorodeoxyadenosine (2CDA) (0.3 mg/kg) and cytosine arabinoside (AraC) (1 g/m(2)) were then administered for 5 days and were followed, after hematological recovery, by maintenance therapy. Both patients had normal complete blood cell counts and no signs of JXG, respectively, 31 and 24 months after diagnosis. PMID- 20589640 TI - New hypotheses about the structure-function of proprotein convertase subtilisin/kexin type 9: analysis of the epidermal growth factor-like repeat A docking site using WaterMap. AB - LDL cholesterol (LDL-C) is cleared from plasma via cellular uptake and internalization processes that are largely mediated by the low-density lipoprotein cholesterol receptor (LDL-R). LDL-R is targeted for lysosomal degradation by association with proprotein convertase subtilisin-kexin type 9 (PCSK9). Gain of function mutations in PCSK9 can result in excessive loss of receptors and dyslipidemia. On the other hand, receptor-sparing phenomena, including loss-of-function mutations or inhibition of PCSK9, can lead to enhanced clearance of plasma lipids. We hypothesize that desolvation and resolvation processes, in many cases, constitute rate-determining steps for protein-ligand association and dissociation, respectively. To test this hypothesis, we analyzed and compared the predicted desolvation properties of wild-type versus gain-of function mutant Asp374Tyr PCSK9 using WaterMap, a new in silico method for predicting the preferred locations and thermodynamic properties of water solvating proteins ("hydration sites"). We compared these results with binding kinetics data for PCSK9, full-length LDL-R ectodomain, and isolated EGF-A repeat. We propose that the fast k(on) and entropically driven thermodynamics observed for PCSK9-EGF-A binding stem from the functional replacement of water occupying stable PCSK9 hydration sites (i.e., exchange of PCSK9 H-bonds from water to polar EGF-A groups). We further propose that the relatively fast k(off) observed for EGF-A unbinding stems from the limited displacement of solvent occupying unstable hydration sites. Conversely, the slower k(off) observed for EGF-A and LDL-R unbinding from Asp374Tyr PCSK9 stems from the destabilizing effects of this mutation on PCSK9 hydration sites, with a concomitant increase in the persistence of the bound complex. PMID- 20589641 TI - Crystal structures of the apo and GDP-bound forms of a cupin-like protein BbDUF985 from Branchiostoma belcheri tsingtauense. PMID- 20589642 TI - Selection of near-native poses in CAPRI rounds 13-19. AB - In CAPRI rounds 13-19, we submitted models that are of acceptable or higher quality for 6 of the total of 13 targets. This success builds on our record in previous CAPRI rounds. The docking problem can be divided into two steps. In the first, translational/rotational and conformational space is searched to generate a pool of docked poses; the success of this search step is measured by whether near-native poses are included in the pool. In the second step, the pool is selected for near-native poses. In our previous assessment of CAPRI results, we suggested that the search problem is largely solved; a remaining problem is to select near-native poses. Our work in these new rounds of CAPRI was guided by this assessment. To solve the selection problem, we used an assortment of criteria on the interfaces of candidate poses. In one extreme, represented by T29, with very little known interface information, our criterion for top models was based on interface prediction. Poses in which the predicted interface residues occurred in interfaces were selected. Our model 1 for T29 was of medium quality. In the other extreme, represented by T40, with reliably known interface information, our selection was solely based on such information. Nine of the ten models submitted for T40 were of high (3 models), medium (4 models), and acceptable (2 models) quality. Our strategy of mixing predicted and known interface information appears to be widely applicable for the selection of near native poses. PMID- 20589643 TI - The targets of CAPRI Rounds 13-19. AB - Seven rounds of CAPRI predictions with a total of 14 targets were held in the period June 2007-November 2009. In addition to protease/inhibitor complexes and complexes with G-proteins, some of the targets displayed novel features presenting new challenges to the predictors: a complex with RNA, a leucine zipper to be built ab initio, and a human-designed protein. Nine targets were unbound or required model building; the other five had a bound component. Thirteen were assessed, and the results show that the predictor and scorer groups submitted two or three-star (medium or high quality) models for eight of them, one-star (acceptable) models for three but failed on the unbound RNA complex and another unbound target. PMID- 20589644 TI - CRK: an evolutionary approach for distinguishing biologically relevant interfaces from crystal contacts. AB - Protein crystals contain two different types of interfaces: biologically relevant ones, observed in protein-protein complexes and oligomeric proteins, and nonspecific ones, corresponding to crystal lattice contacts. Because of the increasing complexity of the objects being tackled in structural biology, distinguishing biological contacts from crystal contacts is not always a trivial task and can lead to wrong interpretation of macromolecular structures. We devised an approach (CRK, core-rim K(a)/K(s) ratio) for distinguishing biologically relevant interfaces from nonspecific ones. Given a protein-protein interface, CRK finds a set of homologs to the sequences of the proteins involved in the interface, retrieves and aligns the corresponding coding sequences, on which it carries out a residue-by-residue K(a)/K(s) ratio (omega) calculation. It divides interface residues into a "rim" and a "core" set and analyzes the selection pressure on the residues belonging to the two sets. We developed and tested CRK on different datasets and test cases, consisting of biologically relevant contacts, nonspecific ones or of both types. The method proves very effective in distinguishing the two categories of interfaces, with an overall accuracy rate of 84%. As it relies on different principles when compared with existing tools, CRK is optimally suited to be used in combination with them. In addition, CRK has potential applications in the validation of structures of oligomeric proteins and protein complexes. PMID- 20589645 TI - Acute megakaryocytic leukemia (AMKL,FAB;M7) with Beckwith-Wiedemann syndrome. AB - Beckwith-Wiedemann syndrome (BWS) is characterized by an accumulation of multiple congenital anomalies. Although patients with BWS are known to have a higher incidence of embryonal tumors, there has been no reports associated with acute leukemia. This report describes the case of a patient with BWS who developed Acute Megakaryocytic Leukemia (AMKL,FAB;M7). Because most patients with BWS present gigantism, the therapy-related toxicity of chemotherapy can be a very serious problem. This patient exhibited no therapy-related toxicity after chemotherapy, suggesting that acute leukemia with BWS may not require a reduction in dosage. PMID- 20589646 TI - The effect of parental mental health on proxy reports of health-related quality of life in children with sickle cell disease. AB - BACKGROUND: The objectives of this study were to evaluate factors that influence agreement between parent-proxy and child self-report of health-related quality of life (HRQL) in sickle cell disease. We hypothesized that the mental health of the parent, parental HRQL and child characteristics would affect agreement. PROCEDURE: In a cross-sectional study of children with sickle cell disease, HRQL of the child and the parent's HRQL and mental health were assessed. The effect of parent and child characteristics on agreement between parent-proxy and child self report of HRQL were determined. RESULTS: Rates of agreement between parent-proxy and child self-report of HRQL ranged between 42% and 49%. Parents with increased symptoms of distress had an increased odds of reporting a worse physical (Odds Ratio (OR) 1.12) and psychosocial HRQL (OR 1.10) compared to the child's self report. Severe sickle cell disease was associated with an increased odds of the parent reporting the child's physical HRQL was worse, (OR 4.68) compared to the child's self-report. CONCLUSIONS: Greater symptoms of distress in the parent are associated with worse parent-proxy report of the child's HRQL. Severe sickle cell disease is associated with greater disagreement between parent-proxy and child self-report of HRQL. These findings broaden our understanding of factors that influence proxy-reporting of a child's HRQL. PMID- 20589647 TI - Analysis of liver transplant outcomes for United Network for Organ Sharing recipients 60 years old or older identifies multiple model for end-stage liver disease-independent prognostic factors. AB - Older recipient age is associated with worse posttransplant survival. Although the median age of liver disease patients undergoing orthotopic liver transplantation (OLT) continues to rise, prognostic factors for posttransplant survival specific to older patients have not been defined. To address this issue, the United Network for Organ Sharing/Organ Procurement and Transplantation Network outcome database was searched to identify prognostic factors for the 8070 liver recipients 60 years old or older who underwent transplantation from 1994 to 2005. Prognostic factors were assessed with univariate analysis and multivariate modeling. The 5 strongest prognostic variables (ventilator status, diabetes mellitus, hepatitis C virus, creatinine levels >/=1.6 mg/dL, and recipient and donor age >or=120 years) were aggregated to define a novel older recipient prognostic score (ORPS). The overall 1- and 5-year posttransplant survival rates were 83% and 67%, respectively. The risk model, created by the assignment of 1 point to each ORPS factor, stratified patient outcomes into distinct prognostic groups at the 1-, 3-, and 5-year posttransplant time points (P < 0.001). The 5 year survival rates for patients with ORPS values of 0, 1, and 2 points were 75%, 69%, and 58%, respectively. Patients who underwent transplantation with an ORPS > 2 points consistently experienced 5-year survival rates of less than 50%. In conclusion, in liver transplant recipients 60 years old or older, the ORPS was able to predict significant and clinically relevant differences in posttransplant survival. By optimization of donor selection for recipients over the age of 60 years, clinical utilization of the ORPS model may enhance organ utilization for all patients awaiting OLT. PMID- 20589648 TI - Continuously improving ifosfamide/mesna: a winning combination. PMID- 20589649 TI - Stereotactic radiotherapy as an alternative to plaque brachytherapy in retinoblastoma. AB - Radioactive plaque brachytherapy has an established role for selected patients with retinoblastoma. Newer non-invasive radiotherapy techniques such as stereotactic conformal radiotherapy (SCR) that uses highly accurate positioning to deliver treatment with small beams may be an interesting alternative to brachytherapy. We report a case treated with SCR and compare the dosimetry with that achievable with brachytherapy. With advantages and disadvantages to both, SCR should more often be considered in the management of RB because of the more homogeneous dose within the target volume and similar or lower doses to surrounding normal tissues. PMID- 20589650 TI - Increased prevalence of risk factors for cardiovascular disease in long-term survivors of acute lymphoblastic leukemia and Wilms tumor treated with radiotherapy. AB - BACKGROUND: Only a few studies have assessed cardiovascular risk factors (CRFs) in childhood cancer survivors. We determined the prevalence of CRFs in long-term survivors of acute lymphoblastic leukemia (ALL) and Wilms tumor. PROCEDURE: Adult survivors of ALL and Wilms tumor treated with radiotherapy and chemotherapy (RT + CT) or treated with chemotherapy alone (CT) were compared with sibling controls. CRFs (hypertension, diabetes mellitus, hypercholesterolemia, obesity, renal insufficiency) and hormonal deficiencies were assessed in each participant. Multivariate logistic regression analysis was used to evaluate the association between CRFs and treatment. RESULTS: Seventy-nine ALL, 62 Wilms tumor survivors, and 69 control subjects (mean ages 24.5, 25.9, and 26 years, respectively) were enrolled. Mean follow-up time since cancer treatment was 20.8 years. In the Wilms RT + CT group significantly more survivors had hypertension (21.6% vs. 1.4%, P < 0.001) and renal insufficiency (8.1% vs. 0%, P = 0.016) compared to controls. There were also more patients with multiple CRFs in the Wilms RT + CT group (16.2% vs. 2.9% in controls, P = 0.019). Almost 15% of ALL RT + CT survivors had growth hormone deficiency. Hypogonadism was seen in 18.9% of survivors in the Wilms RT + CT group. We observed no significant differences between CT-treated survivors of both malignancies and controls. The adjusted odds ratio for the occurrence of at least one CRF was 2.6 increased for survivors following abdominal radiotherapy. Treatment with CT alone was not associated with the occurrence of multiple CRFs. CONCLUSIONS: Long-term survivors of ALL and Wilms tumor have unfavorable CRFs due to previous RT not CT. PMID- 20589652 TI - Refractory dilated cardiomyopathy associated with metastatic neuroblastoma. AB - A 2-year-old African American male presented with heart failure and an abdominal mass. Computerized tomography (CT) scan revealed a 7 cm adrenal lesion, confirmed as poorly differentiated neuroblastoma (NB). CT and meta-iodobenzoguanidine (MIBG) scans identified multiple metastases, but cardiac MIBG imaging was absent. Cardiac ejection fraction (EF) was 8% with 7% shortening fraction. The patient underwent six cycles of chemotherapy and investigational immunotherapy. Cardiac function improved to 26% EF. However, the tumor proved unresponsive to treatment. The patient died from stage IV congestive heart failure (CHF) and progressive NB. Autopsy confirmed dilated cardiomyopathy with endocardial fibroelastosis. PMID- 20589651 TI - Phase I study of decitabine with doxorubicin and cyclophosphamide in children with neuroblastoma and other solid tumors: a Children's Oncology Group study. AB - BACKGROUND: Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors. PROCEDURE: Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hr decitabine infusion for 7 days, followed by doxorubicin (45 mg/m(2)) and cyclophosphamide (1 g/m(2)) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase 8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post treatment peripheral blood and bone marrow cells. RESULTS: The maximum-tolerated dose of decitabine was 5 mg/m(2)/day for 7 days. Dose-limiting toxicities at 10 mg/m(2)/day were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for > or = 4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post treatment (12/20 and 14/16, respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis. CONCLUSION: Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deacetylase inhibitors should be explored. PMID- 20589653 TI - Brucellosis in a patient with end-stage liver disease undergoing liver transplantation: successful treatment with tigecycline. PMID- 20589654 TI - Fanconi anemia gene mutations are not involved in sporadic Wilms tumor. AB - Bi-allelic germline mutations of the Fanconi anemia (FA) genes, PALB2/FANCN and BRCA2/FANCD1, have been reported in a few Wilms tumor (WT) patients with an atypical FA phenotype. Therefore, we screened a random cohort of 47 Dutch WT cases for germline mutations in these two FA-genes by DNA sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). Although several cases appeared to carry missense variants, no bi-allelic pathogenic mutations were identified, indicating that bi-allelic mutations in these FA-genes do not contribute significantly to the occurrence of WT. PMID- 20589655 TI - Burkitt lymphoma: residual abdominal tumor volume after induction therapy correlates with outcome. AB - Staging investigations in the Malawi 2003 BL protocol included abdominal ultrasonography. This sometimes demonstrated tumor that was not palpable. Patients with no palpable tumor following induction with three courses of cyclophosphamide were considered to be in remission, although residual intraabdominal tumor was documented in some by chance. We repeated ultrasonography on day 29 on 22 new patients with non-palpable abdominal BL following induction. The relapse rate after 1 year correlated with the largest residual tumor volume, and was 17% for tumors 0-35 ml, and 75% for tumors > or = 35 ml in volume. Risk patients were thus identified. PMID- 20589657 TI - Matched unrelated umbilical cord blood transplantation for a patient with chemotherapy resistant Wilms tumor. AB - We report a patient with chemotherapy refractory Wilms tumor who underwent an unrelated donor cord blood transplant for chemotherapy refractory disease. The preparative regimen consisted of busulfan, melphalan, and anti-thymocyte globulin, and was well tolerated. This patient did not experience significant toxicity related to the chemotherapy regimen and did not develop any graft versus host disease from his HLA (A, B, DR) 6/6 matched cord blood transplant. Follow-up CT scans 2 years post-transplant have shown no evidence of disease progression, with only a few pulmonary nodules remaining, which are unchanged in size from his pre-transplant CT scan. It is possible that high-dose chemotherapy and stem cell transplantation can be curative in patients with tumors that are non-responsive to conventional chemotherapy. PMID- 20589656 TI - Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. AB - BACKGROUND: Alkylating agents are commonly used in the treatment of childhood malignant gliomas. Overexpression of O(6)-methylguanine-DNA methyltransferase (MGMT) constitutes an important mechanism for resistance to such agents, and MGMT status has been associated with outcome in several recent trials. Deficiency in mismatch repair (MMR) function has been implicated in preclinical studies as an additional potential mechanism of resistance to methylating agents, such as temozolomide, independent of tumor MGMT status. However, the frequency of this abnormality as a clinical resistance mechanism in childhood malignant gliomas has not been well characterized. METHODS: To address this issue, we examined the frequency of microsatellite instability (MSI), a marker of defective MMR, in a series of 68 tumors, derived from newly diagnosed patients treated on the Children's Cancer Group 945 study, and the Children's Oncology Group ACNS0126 and 0423 studies. MSI was assessed using a panel of six microsatellite markers, including BAT-25, BAT-26, CAT-25, D2S123, D5S346, and D17S250. MGMT immunoreactivity was assessed in parallel to allow comparison of the relative incidence of MGMT overexpression and MSI. RESULTS: Only three tumors had high level MSI involving three or more markers; the remainder had no MSI at any of the loci examined. These children did not have unusual features in terms of their outcome. In contrast to the infrequency of MSI, 25 tumors (37%) exhibited MGMT overexpression as assessed by immunohistochemistry. None of the tumors with MSI exhibited overexpression of MGMT. CONCLUSION: MMR deficiency is an infrequent contributor to initial alkylator resistance in children with malignant gliomas. PMID- 20589658 TI - Psychosocial functioning and career decision-making in Israeli adolescent and young adult cancer survivors. AB - OBJECTIVES: This study examined how dispositional optimism, health vulnerability, and time perspective were related to adolescent and young adult (AYA) cancer survivors' career decision-making (CDM) and quality of life (QOL). Secondarily, how cultural factors relate to CDM and QOL among Israeli-Jewish and Israeli-Arab cancer survivors was explored. METHODS: Fifty-one cancer survivors (68.6% females, 80.4% Israeli-Jewish, 19.6% Israeli-Arab, M(age) = 21.45 years), at least 6 months post-active treatment (M(time) = 5.75 years) completed self-report questionnaires. RESULTS: Multiple regression analyses indicated that optimism, vulnerability, and past negative, present fatalistic, and future time perspective were significantly associated with QOL (F(6, 47) = 6.80, P < 0.001) and CDM (F(6, 47) = 2.46, P < 0.04). Perceived vulnerability explained the main portion of QOL variance with greater vulnerability associated with lowered QOL (beta = 0.33, P < 0.001). Optimism was positively associated with QOL (beta = 0.55, P < 0.02). Greater present fatalistic time perspective was associated with greater CDM difficulties (beta = 0.32, P < 0.05). Multivariate analyses indicated greater past negative time perceptions (F(1, 46) = 8.92, P < 0.005) and fatalism about the future (F(1, 46) = 5.90, P < 0.02) among Israeli-Arabs as compared to Israeli Jewish survivors. Israeli-Jewish survivors were more optimistic than Israeli-Arab survivors (F(1, 46) = 3.48, P < 0.065). CONCLUSIONS: Vulnerability, optimism, and time perspective were significantly associated with QOL and CDM among Israeli AYA cancer survivors. Israeli-Arabs viewed their pasts and futures more negatively and reported lower optimism than Israeli-Jews. Implications for future research and interventions were considered. PMID- 20589659 TI - Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation. AB - BACKGROUND: Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown. METHODS: Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively. RESULTS: Thirty-seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P < 0.001) and death (HR = 16.6, P < 0.01) in the neurosphere forming group. Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors. Overall survival (OS) was significantly worse for neurosphere-forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in the glial group. Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment. Neurosphere formation was an independent predictor of diminished PFS of glial tumors after adjusting for grade. Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neurosphere formation remained predictive of progression whereas Ki67 did not. CONCLUSIONS: Neurosphere formation is more predictive of pediatric brain tumor progression than semi-quantitative Ki67 staining. Pediatric brain tumor derived neurospheres may provide a predictive model for preclinical explorations. PMID- 20589660 TI - An uncommon case of a child with del(5q) and hypocellular myelodysplastic syndrome. PMID- 20589661 TI - Development of secondary T-cell acute lymphoblastic leukemia in a child with hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is a severe life-threatening disorder, characterized by hyperactivation of macrophages. A 12-year-old female was referred to our center; the diagnosis of HLH was made for the patient and immunosuppressive regimen was started. After a 2-year follow-up, the patient developed secondary T-cell acute lymphoblastic leukemia (T-ALL), confirmed by flow cytometric studies. Treatment was started based on T-ALL protocol, but the patient died because of relapse and sepsis. This case highlights the issue of secondary malignancy following HLH and demonstrates the need for continued follow up in such patients. PMID- 20589662 TI - Danaparoid as the prophylaxis for hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation in childhood hematological malignancy. AB - BACKGROUND: Veno-occlusive disease (VOD) is a regimen-related toxicity that occurs in the early phase of hematopoietic stem cell transplantation (HSCT). Therapeutic modalities for established VOD are limited, and severe VOD characterized by multiple organ failure is associated with a fatal prognosis despite intensive supportive care. PROCEDURE: We analyzed the data of 95 consecutive allogeneic HSCT for childhood hematological malignancies, and assessed the efficacy of our VOD prophylaxis regimen based on danaparoid (n = 48), comparing with historical control regimen based on dalteparin (n = 47). RESULTS: Eight patients (danaparoid cohort in one; dalteparin cohort in seven) developed VOD on day +30 (median onset, day +22; range, day +11 to day +28) after HSCT. The probability of developing VOD for the danaparoid cohort was 2% (95% CI, 0-6%) and that of the dalteparin cohort was 15% (95% CI, 5-26%). In the Cox hazard proportional model, the danaparoid cohort had a significant advantage over the dalteparin cohort for the prophylaxis of VOD (hazard ratio (HR), 0.0; 95% CI, 0.0-0.3; P < 0.01) without increasing hemorrhagic events. CONCLUSIONS: Our findings suggest that danaparoid may have promise for the prophylaxis of VOD after allogeneic HSCT and further randomized studies are warranted. PMID- 20589666 TI - Low anthracyclines doses-induced cardiotoxicity in acute lymphoblastic leukemia long-term female survivors. AB - BACKGROUND: High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long-term survivors of ALL. PROCEDURE: Echocardiograms were performed on 62 long-term ALL survivors, without any overt or sub-clinical signs or symptoms of heart failure. The interval after stopping therapy was 12.6 +/- 4.3 years; the mean cumulative dose of anthracyclines was 228.2 +/- 42.3 mg/m(2) . Left ventricular (LV) structure and function were studied by echocolor Doppler. An age, gender and body surface area (BSA) matched group of healthy subjects was used as controls. Cardiac data were analyzed before and after BSA normalization. RESULTS: Long term survivors of ALL, showed a lower LV mass index, interventricular septal and posterior wall thickness, which were independently related to gender and to age at which the ALL diagnosis was made. Data analyzed according to gender showed that abnormalities were confined to the female group. No alterations were observed in the ALL male group versus the corresponding control group. No relationship was observed between the echocardiografic abnormalities and the duration of follow-up or the anthracycline mean dose employed. CONCLUSIONS: In the absence of any signs or symptoms of heart failure, female ALL survivors treated with low cumulative anthracycline doses, showed a reduced LV mass and wall thickness. This suggests that in female ALL survivors an echocardyographic follow-up should be recommended. PMID- 20589667 TI - Production of a non-triple helical collagen alpha chain in transgenic silkworms and its evaluation as a gelatin substitute for cell culture. AB - We generated transgenic silkworms that synthesized human type I collagen alpha1 chain [alpha1(I) chain] in the middle silk glands and secreted it into cocoons. The initial content of the recombinant alpha1(I) chain in the cocoons of the transgenic silkworms was 0.8%. The IE1 gene, a trans-activator from the baculovirus, was introduced into the transgenic silkworm to increase the content of the chain. We also generated silkworms homozygous for the transgenes. These manipulations increased the alpha1(I) chain content to 8.0% (4.24 mg per cocoon). The alpha1(I) chain was extracted and purified from the cocoons using a very simple method. The alpha1(I) chain contained no hydroxyprolines due to the absence of prolyl-hydroxylase activity in the silk glands. Circular dichroism analysis showed that the secondary structure of the alpha1(I) chain is similar to that of denatured type I collagen, demonstrating the absence of the triple helical structure. Human skin fibroblasts were seeded on the alpha1(I) chain coated dishes. The cells attached and spread, although at decreased chain concentrations the spreading rate was lower than that of the collagen and gelatin. Cynomolgus monkey embryonic stem cells cultured on the alpha1(I) chain coated dishes maintained an undifferentiated state after 30 passages, and their pluripotency was confirmed by teratoma formation in severe combined immunodeficient mice. These results show that the recombinant human alpha1(I) chain is a promising candidate biomaterial as a high-quality and safe gelatin substitute for cell culture. PMID- 20589669 TI - Defining process design space for monoclonal antibody cell culture. AB - The concept of design space has been taking root as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. During mapping of the process design space, the multidimensional combination of operational variables is studied to quantify the impact on process performance in terms of productivity and product quality. An efficient methodology to map the design space for a monoclonal antibody cell culture process is described. A failure modes and effects analysis (FMEA) was used as the basis for the process characterization exercise. This was followed by an integrated study of the inoculum stage of the process which includes progressive shake flask and seed bioreactor steps. The operating conditions for the seed bioreactor were studied in an integrated fashion with the production bioreactor using a two stage design of experiments (DOE) methodology to enable optimization of operating conditions. A two level Resolution IV design was followed by a central composite design (CCD). These experiments enabled identification of the edge of failure and classification of the operational parameters as non-key, key or critical. In addition, the models generated from the data provide further insight into balancing productivity of the cell culture process with product quality considerations. Finally, process and product-related impurity clearance was evaluated by studies linking the upstream process with downstream purification. Production bioreactor parameters that directly influence antibody charge variants and glycosylation in CHO systems were identified. PMID- 20589670 TI - Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process. AB - The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production. PMID- 20589671 TI - In situ effective diffusion coefficient profiles in live biofilms using pulsed field gradient nuclear magnetic resonance. AB - Diffusive mass transfer in biofilms is characterized by the effective diffusion coefficient. It is well documented that the effective diffusion coefficient can vary by location in a biofilm. The current literature is dominated by effective diffusion coefficient measurements for distinct cell clusters and stratified biofilms showing this spatial variation. Regardless of whether distinct cell clusters or surface-averaging methods are used, position-dependent measurements of the effective diffusion coefficient are currently: (1) invasive to the biofilm, (2) performed under unnatural conditions, (3) lethal to cells, and/or (4) spatially restricted to only certain regions of the biofilm. Invasive measurements can lead to inaccurate results and prohibit further (time-dependent) measurements which are important for the mathematical modeling of biofilms. In this study our goals were to: (1) measure the effective diffusion coefficient for water in live biofilms, (2) monitor how the effective diffusion coefficient changes over time under growth conditions, and (3) correlate the effective diffusion coefficient with depth in the biofilm. We measured in situ two dimensional effective diffusion coefficient maps within Shewanella oneidensis MR 1 biofilms using pulsed-field gradient nuclear magnetic resonance methods, and used them to calculate surface-averaged relative effective diffusion coefficient (D(rs)) profiles. We found that (1) D(rs) decreased from the top of the biofilm to the bottom, (2) D(rs) profiles differed for biofilms of different ages, (3) D(rs) profiles changed over time and generally decreased with time, (4) all the biofilms showed very similar D(rs) profiles near the top of the biofilm, and (5) the D(rs) profile near the bottom of the biofilm was different for each biofilm. Practically, our results demonstrate that advanced biofilm models should use a variable effective diffusivity which changes with time and location in the biofilm. PMID- 20589672 TI - Cell line-specific control of recombinant monoclonal antibody production by CHO cells. AB - In this study we compare the cellular control of recombinant human IgG(4) monoclonal antibody (Mab) synthesis in different CHO cell lines. Based on comprehensive empirical analyses of mRNA and polypeptide synthetic intermediates we constructed cell line-specific mathematical models of recombinant Mab manufacture in seven GS-CHO cell lines varying in specific production rate (qMab) over 350-fold. This comparative analysis revealed that control of qMab involved both genetic construct and cell line-specific factors. With respect to the former, all cell lines exhibited excess production of light chain (LC) mRNA and polypeptide relative to heavy chain (HC) mediated by more rapid LC transcription and enhanced LC mRNA stability. Downstream of this, cell lines differed markedly in their relative rates of recombinant mRNA translation, Mab assembly and secretion although HC mRNA abundance and the rate of HC translation generally exerted most control over qMab--the latter being directly proportional to qMab. This study shows that (i) cell lines capable of high qMab exceed a threshold functional competency in all synthetic processes, (ii) the majority of cells in parental and transfected cell populations are functionally limited and (iii) cell engineering strategies to increase Mab production should be cell line specific. PMID- 20589673 TI - Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. AB - Thermal inkjet printing technology has been applied successfully to cell printing. However, there are concerns that printing process may cause cell damages or death. We conducted a comprehensive study of thermal inkjet printed Chinese hamster ovary (CHO) cells by evaluating cell viability and apoptosis, and possible cell membrane damages. Additionally, we studied the cell concentration of bio-ink and found optimum printing of concentrations around 8 million cells per mL. Printed cell viability was 89% and only 3.5% apoptotic cells were observed after printing. Transient pores were developed in the cell membrane of printed cells. Cells were able to repair these pores within 2 h after printing. Green fluorescent protein (GFP) DNA plasmids were delivered to CHO-S cells by co printing. The transfection efficiency is above 30%. We conclude that thermal inkjet printing technology can be used for precise cell seeding with minor effects and damages to the printed mammalian cells. The printing process causes transient pores in cell membranes, a process which has promising applications for gene and macroparticles delivery to induce the biocompatibility or growth of engineered tissues. PMID- 20589674 TI - Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration. AB - Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury. PMID- 20589675 TI - Crystallization of recombinant human growth hormone at elevated pressures: pressure effects on PEG-induced volume exclusion interactions. AB - Crystallization of recombinant human growth hormone (rhGH) at elevated pressures was investigated in the presence of 6,000 molecular weight poly(ethylene glycol; PEG-6000). Crystallization of rhGH at atmospheric pressure occurred at a protein concentration of 15 mg/mL in 6% PEG-6000. Crystallization did not occur in the same solutions at 250 MPa. In contrast, at a pressure of 250 MPa in the presence of 8% PEG-6000, rhGH readily crystallized from solutions containing 35 mg/mL rhGH, whereas amorphous precipitate formed in the same solutions at atmospheric pressure. Osmotic virial coefficients were determined from static light scattering measurements and combined with a hard-sphere activity coefficient model to predict rhGH activity coefficients as a function of pressure and PEG concentration. Predicted activity coefficients quantitatively matched those determined from equilibrium solubility measurements. The ability to adjust the thermodynamic non-ideality with pressure provides a valuable tool to study protein crystallization in addition to providing a methodology for obtaining crystals at elevated pressures. PMID- 20589676 TI - Nonfilter and filter cigarette consumption and the incidence of lung cancer by histological type in Japan and the United States: analysis of 30-year data from population-based cancer registries. AB - Shifts in the histologic type of lung cancer accompanying changes in lung cancer incidence have been observed in Japan and the United States. We examined the association between the shift in tobacco design from nonfilter to filter cigarettes with changes in the incidence of adenocarcinoma (AD) and squamous cell carcinoma (SQ) of the lung. We compiled population-based incidence data from the Surveillance, Epidemiology and End Results in the United States (1973-2005) and from selected Japanese cancer registries (1975-2003). Trends in age-standardized rates of lung cancer incidence by histologic type were characterized using joinpoint analyses. A multiple regression framework was used to examine the relationship between tobacco use and incidence by histologic type. We observed that AD has replaced SQ as the most frequent histologic type in males and females in both Japan and the United States. Filter cigarette consumption was positively associated with the incidence of AD, with time lags of 25 and 15 years in Japan and the United States, respectively ( beta(2)(AD)): 1.946 * 10(-3) , p < 0.001 and 3.142 * 10(-3) , p < 0.001). In contrast, nonfilter cigarette consumption was positively associated with the incidence of SQ, with time lags of 30 and 20 years in Japan and the United States, respectively (beta (SQ)(2) ): 0.464 * 10(-3) , p = 0.006 and 0.364 * 10(-3) , p = 0.008). In conclusion, the shift from nonfilter to filter cigarettes appears to have merely altered the most frequent type of lung cancer, from SQ to AD. PMID- 20589677 TI - Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis. AB - Comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized-controlled trial to compare cost effectiveness of screening with either one round of immunochemical fecal occult blood testing (I-FOBT; OC-Sensor(r)), one round of guaiac FOBT (G-FOBT; Hemoccult II(r)) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third-party payer perspective in a Markov model with first- and second-order Monte Carlo simulation. Costs were measured in Euros (?), effects in life-years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I-FOBT dominated the alternatives: after one round of I-FOBT screening, a hypothetical person would on average gain 0.003 life-years and save the health care system ?27 compared with G FOBT and 0.003 life years and ?72 compared with no screening. Overall, in 4,460,265 Dutch aged 50-75 years, after one round I-FOBT screening, 13,400 life years and ?320 million would have been saved compared with no screening. I-FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I-FOBT dominated G-FOBT and no screening with or without accounting for uncertainty. PMID- 20589679 TI - Prognostic but not predictive role of platelet-derived growth factor receptors in patients with recurrent glioblastoma. AB - Platelet-derived growth factor receptor (PDGFR) signaling has been implicated in the pathogenesis of glioblastomas and represents a target for the tyrosine kinase inhibitor imatinib. To examine the prognostic or predictive role of PDGFRs in recurrent glioblastomas, expression was examined in tumor samples of 101 patients of CSTI571BDE40, a randomized trial comparing hydroxyurea monotherapy and a combination of hydroxyurea and imatinib. Furthermore, PDGFRalpha phosphorylation was investigated using in situ proximity ligation assay. PDGFRalpha protein was expressed in 33% of tumors and was associated with male sex, young age, presence of R132H mutated isocitrate dehydrogenase 1 protein and short median survival (142 vs. 187 days, p = 0.028). Tumor PDGFRalpha phosphorylation was also associated with short survival (p = 0.030). The subset of patients with PDGFRalpha positive glioblastoma did not have longer survival on treatment with hydroxyurea and imatinib compared with hydroxyurea monotherapy. In conclusion, both PDGFRalpha protein expression and phosphorylation status had a prognostic role in recurrent glioblastomas but did not define a group that showed benefit from the combination therapy consisting of hydroxyurea and imatinib. PMID- 20589680 TI - 1,25-Dihydroxyvitamin D(3) may be insufficient to prevent corticosteroid-induced osteoporosis in patients with early rheumatoid arthritis: comment on the article by Colin et al. PMID- 20589681 TI - Inhibitors of p38 suppress cytokine production in rheumatoid arthritis synovial membranes: does variable inhibition of interleukin-6 production limit effectiveness in vivo? AB - OBJECTIVE: The activity of p38 MAPK regulates lipopolysaccharide (LPS)-stimulated production of key proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). Consequently, p38 MAPK inhibitors have attracted considerable interest as potential treatments of rheumatoid arthritis (RA), and studies in murine models of arthritis have yielded promising results. However, the performance of several compounds in human clinical trials has been disappointing. At present, the reason for this poor performance is unclear. The aim of this study was to examine the effects of p38 inhibitors on both diseased and normal human tissue and cells, in order to test whether this kinase still plays a critical role in cytokine production under conditions of chronic inflammation. METHODS: Proinflammatory and antiinflammatory cytokine production was monitored after treatment of primary human monocytes, macrophages, and RA synovial membrane cultures with p38 MAPK inhibitor compounds. The following 3 inhibitors were used in these studies: SB-203580 (inhibits the alpha and beta isoforms), BIRB-796 (inhibits the alpha, beta, gamma, and delta isoforms), and a novel, structurally distinct p38 MAPK inhibitor, SB-731445 (inhibits the alpha and beta isoforms). RESULTS: SB-731445 and SB-203580 produced profound inhibition of spontaneous production of proinflammatory cytokines (TNFalpha and interleukin-1 [IL-1]) in both RA membrane cultures and LPS-stimulated primary human monocytes. However, this and other p38 MAPK inhibitors produced a significant increase in IL-6 production by LPS-stimulated primary human macrophages and a decrease in IL-10 production by all cell types examined. CONCLUSION: The potentially proinflammatory consequences of these activities (decreased IL-10 production and increased IL-6 production) may offer some explanation for the inability of p38 MAPK inhibitors to provide the therapeutic benefit that had been hoped for in RA. PMID- 20589683 TI - Knockdown of Fcgamma receptor III in an arthritic temporomandibular joint reduces the nociceptive response in rats. AB - OBJECTIVE: Fcgamma receptor III (FcgammaRIII; CD16) is a receptor expressed on immune cells that selectively binds IgG molecules. IgG binding results in cellular activation and cytokine release. IgG is an important factor in arthritis and can be found in the arthritic temporomandibular joint (TMJ). We undertook this study to test the hypothesis that a reduction in FcgammaRIII expression in TMJ tissues would reduce the nociceptive and inflammatory responses in an inflamed joint. METHODS: Small interfering RNA (siRNA), either naked or complexed with linear polyethyleneimine, was injected into the superior joint space of the TMJ in rats. After administration of siRNA the joint was injected with saline or with Freund's complete adjuvant to induce arthritis. Nociceptive responses were quantitated in the rat by measuring the animal's meal duration. FcgammaRIII expression in the TMJ tissue was assayed by immunocytochemistry or Western blotting. Cleavage of FcgammaRIII transcript was then assayed by 5' rapid amplification of complementary DNA ends. Interleukin-1beta (IL-1beta) and IgG content was measured in the TMJ tissue by enzyme-linked immunosorbent assay. RESULTS: Injection of FcgammaRIII siRNA reduced the amount of FcgammaRIII in the TMJ tissues, and the transcript was cleaved in a manner consistent with an RNA interference mechanism. Moreover, injection of FcgammaRIII siRNA reduced the nociceptive response of rats with an arthritic TMJ and reduced the amount of the proinflammatory cytokine IL-1beta. CONCLUSION: FcgammaRIII contributes to the pain resulting from inflammatory arthritis of the TMJ, and siRNA has the potential to be an effective treatment for this disorder. PMID- 20589684 TI - Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. AB - OBJECTIVE: Abdominal adiposity, especially visceral adiposity, is emerging as a recognized cardiometabolic risk factor. This study was undertaken to investigate how abdominal fat is distributed in rheumatoid arthritis (RA), and its RA-related determinants. METHODS: Men and women with RA were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis. Participants underwent anthropometric studies and quantification of visceral and subcutaneous fat areas (VFA and SFA) using abdominal computed tomography. RESULTS: A total of 131 RA patients were compared with 121 controls. Despite similar body mass index and waist circumference between the RA and control groups, the adjusted mean VFA was 45 cm2 higher (+51%) in male RA patients versus male controls (P = 0.005), but did not significantly differ by RA status in women. The adjusted mean SFA was 119 cm2 higher (+68%) in female RA patients versus female controls (P < 0.001), but did not significantly differ by RA status in men. Elevated VFA (>=75th percentile) was associated with a significantly higher adjusted probability of having an elevated fasting glucose level, hypertension, or meeting the composite definition of the metabolic syndrome in the RA group compared with controls. Within the RA group, rheumatoid factor seropositivity and higher cumulative prednisone exposure were significantly associated with a higher mean adjusted VFA. Higher C-reactive protein levels and lower Sharp/van der Heijde scores were significantly associated with both VFA and SFA. CONCLUSION: The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations. PMID- 20589685 TI - MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. AB - OBJECTIVE: MicroRNA (miRNA) have received increasing attention as posttranscriptional regulators that fine-tune the homeostasis of the inflammatory response. This study aimed to clarify whether miR-125a, which was identified in a pilot expression profiling step, is involved in the inflammatory chemokine pathway in systemic lupus erythematosus (SLE). METHODS: Independent verification of miR-125a expression in amplified samples from SLE patients and normal controls was performed by TaqMan quantitative polymerase chain reaction (PCR) analysis. A combination of 3 bioinformatic prediction techniques and reporter gene assays was used to identify miR-125a targets. In vitro systems of overexpression by transfection and inducible expression by stimulation were performed to investigate the function of miR-125a, which was followed by real-time quantitative PCR and enzyme-linked immunosorbent assay. RESULTS: In SLE patients, the expression of miR-125a was reduced and the expression of its predicted target gene, KLF13, was increased. Bioinformatics predicted that miR-125a base-paired with sequences in the 3'-untranslated region of KLF13. Overexpression of miR-125a led to a significant reduction in the expression of RANTES and KLF13. MicroRNA 125a inhibited endogenous KLF13 expression in a dose-dependent manner, as determined using gain- and loss-of-function methods. A luciferase reporter system confirmed the miR-125a binding sites. Notably, miR-125a expression was induced in T cells in a dose- and time-dependent manner. Finally, the introduction of miR 125a into T cells from SLE patients alleviated the elevated RANTES expression. CONCLUSION: MicroRNA-125a negatively regulates RANTES expression by targeting KLF13 in activated T cells. The underexpression of miR-125a contributes to the elevated expression of RANTES in SLE. Our findings extend the role of miRNA in the pathogenesis of lupus and provide potential strategies for therapeutic intervention. PMID- 20589688 TI - The nerve of osteoarthritis pain. AB - OBJECTIVE: Cumulative data suggest that central sensitization may contribute to pain in osteoarthritis (OA) and present with symptoms typically associated with neuropathic pain (NP). We evaluated the responses from focus group participants on the knee OA pain experience for pain descriptions that suggest NP. METHODS: Focus group transcripts were analyzed by 2 independent assessors for unprompted use of pain descriptors that suggested NP. Items from validated NP symptom-based questionnaires were used to guide the analysis. Data on sociodemographic factors, duration of knee OA, and OA disease and pain severity (using the Western Ontario and McMaster Universities Osteoarthritis Index and a numerical rating scale) were obtained from questionnaires administered after focus group completion. These factors were compared among participants who did and did not use descriptors that suggested NP. RESULTS: Transcripts from 80 knee OA participants were analyzed. A range of NP descriptors was used to characterize their knee symptoms, including burning, tingling, numbness, and pins and needles. The proportion of participants who used NP descriptors was 0.34 (95% confidence interval 0.24-0.45). Those who used NP descriptors were younger (P = 0.003) and, although not statistically different, more likely to be women, with higher pain intensity and OA severity and longer OA duration, than those who did not use NP descriptors. CONCLUSION: During focus groups, a subset of adults with chronic, symptomatic knee OA used pain quality descriptors that were suggestive of NP. Elicitation of NP descriptors in people with OA may help identify those who could benefit from further evaluation and perhaps treatment for NP. PMID- 20589689 TI - Association of inflammatory mediators with premature atherosclerosis in rheumatoid arthritis and healthy controls: comment on the article by Rho et al. PMID- 20589690 TI - Efficacy of cardiorespiratory aerobic exercise in rheumatoid arthritis: meta analysis of randomized controlled trials. AB - OBJECTIVE: Several lines of evidence have emphasized an improvement in aerobic capacity and muscle strength after physical exercise programs in rheumatoid arthritis (RA) patients. Our objective was to evaluate the efficacy of aerobic exercises in RA on quality of life, function, and clinical and radiologic outcomes by a systematic literature review and a meta-analysis. METHODS: A systematic literature search was performed in the Medline, EMBase, and Cochrane databases up to July 2009 and in the abstracts presented at rheumatology scientific meetings during the last 5 years. Randomized controlled trials (RCTs) comparing aerobic exercises with non-aerobic interventions in RA patients were included. Outcomes studied were postintervention quality of life, function assessed by the Health Assessment Questionnaire (HAQ), a pain visual analog scale (VAS), joint count, the Disease Activity Score in 28 joints (DAS28), and radiologic damage. Efficacy was assessed by standardized mean differences (SMDs; difference between groups of mean outcome variation from baseline/SD at baseline) of aerobic exercises versus non-aerobic rehabilitation. Heterogeneity was tested. SMDs were pooled by a meta-analysis using the inverse of variance model. RESULTS: Fourteen RCTs, including 1,040 patients, met the inclusion criteria. Exercise improved the postintervention quality of life (SMD 0.39, P < 0.0001), HAQ score (SMD 0.24, P = 0.0009), and pain VAS (SMD 0.31, P = 0.02). Exercise in this RA population appeared safe, since global compliance, DAS28, and joint count were similar in both groups. CONCLUSION: Cardiorespiratory aerobic conditioning in stable RA appears to be safe and improves some of the most important outcome measures. However, the degree of the effect of aerobic exercise on the abovementioned parameters is small. PMID- 20589692 TI - Osteoporosis screening, prevention, and treatment in systemic lupus erythematosus: application of the systemic lupus erythematosus quality indicators. AB - OBJECTIVE: Osteoporosis and fragility fractures are associated with significant morbidity for patients with systemic lupus erythematosus (SLE). New quality indicators (QIs) for SLE advise bone mineral density testing, calcium and vitamin D use, and antiresorptive or anabolic treatment for specific subgroups of patients receiving high-dose steroids. METHODS: Subjects were participants in the University of California, San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with physician-confirmed SLE, in 2007-2008. Patients responded to an annual telephone survey and were queried regarding demographic, clinical, and other health care-related variables. Multiple logistic regression was used to predict receipt of care per the QIs described above. RESULTS: One hundred twenty-seven patients met the criteria for the formal definitions of the denominators for QI I (screening) and QI II (calcium and vitamin D); 91 met the formal criteria for QI III (treatment). The proportions of patients receiving care consistent with the QIs were 74%, 58%, and 56% for QIs I, II, and III, respectively. In a sensitivity analysis of all steroid users (n = 427 for QI I and II and n = 224 for QI III), rates were slightly lower. Predictors of receiving care varied by QI and by denominator; however, female sex, older age, white race, and longer disease duration were associated with higher-quality care. CONCLUSION: Bone health-related care in this community-based cohort of SLE patients is suboptimal. Quality improvement efforts should address osteoporosis prevention and care among all SLE patients, especially those receiving high-dose, prolonged steroids. PMID- 20589693 TI - A proposed framework to standardize the neurocognitive assessment of patients with pediatric systemic lupus erythematosus. AB - OBJECTIVE: To develop and propose a standardized battery of neuropsychological tests for the assessment of cognitive functioning of children and adolescents with pediatric systemic lupus erythematosus (SLE). METHODS: A committee of health care professionals involved in the assessment of pediatric SLE patients reviewed the literature to identify cognitive domains most commonly affected in pediatric SLE and in adult SLE. They then reviewed the standardized tests available for children and adolescents that assess the cognitive domains identified. Through a structured consensus formation process, the committee considered the psychometric characteristics and durations of the tests. RESULTS: A test battery was developed that appears suitable to provide a comprehensive assessment of cognitive domains commonly affected by pediatric SLE within a 2.5-hour period. CONCLUSION: It is hoped that the consistent use of this reliable and efficient battery increases the practicality of routine evaluations in pediatric SLE, enabling between-cohort comparisons and facilitating the longitudinal assessment of individual patients over time. PMID- 20589694 TI - Can peak work rate predict peak oxygen uptake in children with juvenile idiopathic arthritis? AB - OBJECTIVE: To examine whether peak work rate (W(peak)) can predict peak oxygen uptake (VO(2peak)) in children with juvenile idiopathic arthritis (JIA). METHODS: Ninety-one patients with JIA with a mean +/- SD age of 11.4 +/- 2.9 years underwent a cardiopulmonary exercise test in which VO(2peak) and W(peak) were determined. A multivariate regression model was used to formulate a regression equation to predict VO(2peak) using W(peak) and anthropometric and demographic details. This regression equation was subsequently cross-validated using an unrelated data set from children with JIA (n = 17). RESULTS: The following linear regression equation to predict VO(2peak) was established: VO(2peak) (liters/minute) = 0.308 + 0.146 x sex (0 = female, 1 = male) + 0.005 x weight (kg) + 0.008 x W(peak) (W) (R(2) = 0.91, standard error of the estimate = 0.18 liter/minute). Using this equation, the predicted VO(2peak) was strongly related to the measured VO(2peak) (r = 0.96, P < 0.0001). Bland and Altman analysis revealed a mean difference of 0.01 liter/minute and limits of agreement between 0.35 and 0.35 liter/minute. CONCLUSION: This study suggests that W(peak) is a strong predictor of VO(2peak) in children with JIA and may be used as a surrogate measure of VO(2peak) in situations where it is not possible to formally assess VO(2peak). PMID- 20589696 TI - Validation of minimal disease activity criteria for psoriatic arthritis using interventional trial data. AB - OBJECTIVE: New criteria for minimal disease activity (MDA) in psoriatic arthritis (PsA) have been developed. The aim is to provide further validation of these criteria using data obtained in interventional trials with infliximab, a drug with proven efficacy in PsA. METHODS: The data were obtained from patients in phase II and III infliximab studies of PsA. In both studies, patients with active PsA were treated with infliximab (5 mg/kg) or placebo followed by a period of treatment with infliximab. Between-group comparisons in terms of those achieving MDA and the relationship of MDA to American College of Rheumatology outcomes, C reactive protein levels, and radiologic progression were performed. RESULTS: In the Infliximab Multinational Psoriatic Arthritis Controlled Trial, 48% (15 of 31) of infliximab-treated patients achieved MDA at week 16, compared with 3% (1 of 32) taking placebo (P < 0.0001). At week 50, 96% of those patients who achieved MDA showed no progression of radiologic disease (increase in the modified Sharp/van der Heijde score of < or = 0), compared with 67% of those who did not achieve MDA (P = 0.012). In the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2, 52% (40 of 77) of infliximab-treated patients achieved MDA at week 24, compared with 21% (17 of 80) receiving placebo (P < 0.001). At week 54, 78% of those patients who achieved MDA had no radiologic progression, compared with 57% of those who did not achieve MDA (P = 0.009). CONCLUSION: Patients with active PsA achieving MDA with effective therapy have a significant reduction in radiographic progression. Aiming for low levels of disease activity can improve the outcome of patients with PsA even in a disease-modifying antirheumatic drug resistant cohort. The new MDA criteria could provide an objective target for treatment in trials and clinical practice. PMID- 20589695 TI - Minimal clinically important differences of disease activity indices in childhood onset systemic lupus erythematosus. AB - OBJECTIVE: To determine the minimal clinically important differences (MCIDs) of validated measures of systemic lupus erythematosus (SLE) disease activity in childhood-onset SLE. METHODS: Childhood-onset SLE patients (n = 98) were followed every 3 months for up to 7 visits (n = 623 total visits). Disease activity measures (European Consensus Lupus Activity Measure, Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, British Isles Lupus Assessment Group, and Responder Index for Lupus Erythematosus [RIFLE]) were completed at the time of each visit. Physician-rated changes in the disease course (clinically relevant improvement, no change, clinically relevant worsening) between visits served as the criterion standard. RESULTS: MCIDs defined by mean change scores with improvement and worsening, or those based on the standard error of measurement with stable disease, were both small and did not discriminate well between disease courses (detection rates for improvement or worsening were all <55%). MCIDs based on discriminant and classification analyses yielded similar results. Alternative MCIDs, defined by a 70% predicted probability of improvement or worsening as per the discrimination analysis, were larger but underestimated the proportion of patients with change. The RIFLE only correctly identified 26% and 8% of episodes of clinically important worsening and improvement of childhood-onset SLE, respectively. CONCLUSION: The MCIDs of childhood-onset SLE disease activity measures are often small but similar to those reported for adults with SLE. Therefore, even small changes in disease activity scores can be clinically relevant. Low correct detection rates of these MCID thresholds for changes in disease course support the notion that worsening and improvement with childhood-onset SLE, or its response to therapy, is unlikely to be captured adequately by validated measures of disease activity alone. PMID- 20589699 TI - Clinical relevance of targeted ultrasound of the fifth metatarsophalangeal joint in an early inflammatory arthritis cohort: comment on the article by Sheane et al. PMID- 20589700 TI - Reporting of corticosteroid use in systemic disease trials: evidence from a systematic review of the potential impact on treatment effect. AB - OBJECTIVE: To study how corticosteroid therapy is planned and described in reports of systemic disease trials and estimate the impact of the between-arm difference in corticosteroid dose on treatment effect. METHODS: We performed a systematic review of PubMed and Cochrane databases on all reports of randomized systemic disease trials with corticosteroids as a cointervention. Data were extracted on the trial characteristics and results, planning of corticosteroid use, and dose. Success rates were adjusted for corticosteroid use for studies with available data and a binary outcome. Because the exact impact of between-arm differences in corticosteroid dose on success rates is unknown, we tested different values for the impact of a difference of 1 unit (1 mg for daily dosage or 250 mg for cumulative dose at the end of the trial). RESULTS: A total of 139 trials were identified, including 79 investigating lupus and 30 investigating vasculitis. Planned management of corticosteroid use was specified in 101 reports (72.7%), with a fully described tapering scheme in 33 (23.7%). Corticosteroid consumption for each arm was given in 60 reports (43.2%), with a comparison of daily or cumulative dosage at the end of the trial in 32 (23.0%). An attempt to adjust for corticosteroid use was described in 2 (1.5%). With a value of 2.5% for the impact of a 1-unit difference in corticosteroid dose, adjustment yielded changes in success rate differences exceeding 10% in 11 (46%) of the 24 reports analyzed. CONCLUSION: For systemic disease trials, use of corticosteroids as a cointervention is often inadequately planned and reported and could affect treatment effect. PMID- 20589701 TI - Acquired factor VIII inhibitor in Sjogren's syndrome. PMID- 20589702 TI - Comparison of radiographic joint space width with magnetic resonance imaging cartilage morphometry: analysis of longitudinal data from the Osteoarthritis Initiative. AB - OBJECTIVE: Magnetic resonance imaging (MRI) and radiography are established imaging modalities for the assessment of knee osteoarthritis (OA). The objective of our study was to compare the responsiveness of radiographic joint space width (JSW) with MRI-derived measures of cartilage morphometry for OA progression in participants from the Osteoarthritis Initiative (OAI). METHODS: This study examined the baseline and 12-month visits of a subset of 150 subjects from the OAI. Measurement of radiographic JSW was facilitated by the use of automated software that delineated the femoral and tibial margins of the joint. Measures of medial compartment minimum JSW and JSW at fixed locations were compared with cartilage morphometry measures derived from MRI. The results were stratified by Kellgren/Lawrence (K/L) scale grade and by tibiofemoral anatomic axis angle. In order to examine the relative responsiveness of various techniques, we calculated the standardized response mean (SRM) between the 2 visits. RESULTS: The SRM for radiographic JSW measured at the optimal location was -0.32 compared with -0.39 for the most responsive MRI measure. For the subgroup with a K/L scale grade of 2 or 3, the most responsive SRM values were -0.34 for radiographic JSW and -0.42 for MRI. CONCLUSION: Our study demonstrates that new measures using a software analysis of digital knee radiographic images are comparable with MRI in detecting OA progression, and potentially superior when considering the cost-effectiveness of the 2 imaging modalities. PMID- 20589703 TI - One-year change in radiographic joint space width in patients with unilateral joint space narrowing: data from the Osteoarthritis Initiative. AB - OBJECTIVE: To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline. METHODS: Cases were selected from a pool of 2,678 subjects enrolled in the Osteoarthritis Initiative cohort. Inclusion criteria for the present study were unilateral medial JSN, bilateral frequent knee pain, and body mass index (BMI) > or = 25 kg/m(2). Baseline and 1-year fixed flexion radiographs of both knees were read (blinded to time point) using an automated algorithm for minimum JSW and JSW at 4 fixed locations in the medial compartment. RESULTS: Sixty-seven participants met the inclusion criteria: 43 women and 24 men, with mean +/- SD age 60 +/- 9 years and mean +/- SD BMI 31 +/- 4 kg/m(2). Thirty-seven subjects (55%) had > or = 1 definite tibiofemoral osteophyte. The average progression in no-JSN knees was comparable with that in JSN knees (approximately -0.2 mm/year). However, JSW change was more variable in no-JSN knees, resulting in standardized response means (SRMs; the mean/SD) of approximately -0.24 in no-JSN knees versus approximately -0.41 in JSN knees on average at the 4 fixed locations, and SRMs of -0.24 and -0.35, respectively, for minimum JSW. Young age and high BMI were associated with increased progression, especially in JSN knees. CONCLUSION: JSN and no-JSN knees progressed at a comparable rate, but a wider distribution of JSW change in no-JSN knees resulted in a poorer sensitivity to change in these knees. PMID- 20589704 TI - Intrauterine diagnosis and management of fetal goiter: a case report. AB - Fetal goiter can be the result of maternal hyperthyroidism treated with antithyroid drugs. Polyhydramnios may be the presenting symptom and can be diagnosed prenatally by sonography. We report a case of fetal goiter diagnosed at 30 weeks of gestation and fetal hypothyroidism confirmed by cordocentesis. Intra amniotic levothyroxine was administered. Onset of preterm labor could not be prevented. The risks and benefits of intrauterine treatment of fetal goitrous hypothyroidism are discussed. PMID- 20589705 TI - Preoperative clinically inapparent leucopenia in patients undergoing neoadjuvant chemotherapy for locally advanced gastric cancer is not a risk factor for surgical or general postoperative complications. AB - BACKGROUND: Since the recent MAGIC trial neoadjuvant chemotherapy has been considered as treatment option for patients with advanced gastric cancer for tumor-downsizing and increasing R0 resection rates. Morbidity was reported in 45% of the patients treated within this randomized trial. Due to myelotoxicity under chemotherapy a part of the patients might undergo surgery with preoperative leucopenia. As leucopenia causes adverse events such as opportunistic infections and fever, it might be considered as a relevant risk factor in the course of surgical treatment. PATIENTS AND METHODS: We analyzed a cohort of neoadjuvantly treated patients (n = 214), which had a clinically inapparent but proven leucopenia (n = 58) before undergoing surgery due to advanced stage gastric cancer. RESULTS: Statistical analysis by Fisher's exact test showed, that there was no significant effect neither on general (P = 0.191) nor on surgery-dependant postoperative complications (P = 0.75). CONCLUSION: Conclusively patients with clinically inapparent leucopenia after neoadjuvant chemotherapy due to advanced stage gastric cancer can be safely operated on without putting them in danger of relevant surgical complications. PMID- 20589707 TI - pT0 prostate cancer after radical prostatectomy. AB - The purpose of our study was to perform a literature review of current data to determine the frequency and correlates of pT0 prostate cancer after radical prostatectomy alone. A comprehensive search was made of MEDLINE and PUBMED. Seven studies were identified involving 18,135 patients with 74 reported pT0 cases. The most frequent correlates from our pooled data of patients with pT0 specimens include preoperative PSA <10 ng/ml, only one positive core biopsy, and Gleason score <7. PMID- 20589706 TI - High pretherapeutic thymidylate synthetase and MRP-1 protein levels are associated with nonresponse to neoadjuvant chemotherapy in oesophageal adenocarcinoma patients. AB - BACKGROUND: The aim of this study was to determine whether pretherapeutic protein expression levels of the excision repair cross-complementing (ERCC1) enzyme, thymidylate synthetase (TS), multidrug-resistance protein 1 (MRP-1) and P glycoprotein (P-gp) are associated with tumour response to cisplatin and fluorouracil (5-FU)-based neoadjuvant chemotherapy in oesophageal adenocarcinomas. METHODS: The expression levels of ERCC1, TS, MDR-1 and P-gp were determined immunohistochemically in pretherapeutic tumour biopsies from 40 oesophageal adenocarcinoma patients and were correlated with histopathological tumour regression and with patient survival. Protein expression was compared to mRNA data, which was previously published for ERCC1, TS and MRP-1 and newly determined for the purpose of this study for MDR-1/P-gp. RESULTS: High-TS and MRP-1 protein expression was correlated with tumour non-response to chemotherapy (P = 0.001 and P = 0.036, respectively). For ERCC-1 and P-gp, no association between pretherapeutic protein expression and response was found. There was no correlation between mRNA levels and protein expression for all investigated markers. Survival analysis revealed a trend towards increased survival for low ERCC-1 expression (P = 0.079). CONCLUSIONS: The pattern of pretherapeutic expression of TS and MRP-1 is related to chemotherapy response in oesophageal adenocarcinoma patients. Immunohistochemical assessment of these markers may be helpful for response prediction. PMID- 20589708 TI - Time windows in retention over the first year-and-a-half of life: spacing effects. AB - The time window construct describes when and how an earlier experience will be enduring. According to the construct, there is a limited period after an event occurs, or time window, in which a second event can retrieve and be integrated with the memory of the first event. The construct also holds that when the integration occurs later in the time window, its effects are more enduring. This study examined the time window construct for session spacing with 6- to 18-month old human infants. Infants of all ages exhibited the retention benefit of two (integrated) sessions only when the second session occurred within the time window, but only 6-month-olds remembered longer when it occurred late in the time window. Combined with 3-month-olds' data, these findings document the generality and predictive validity of the time window construct throughout the infancy period with one modification: Integration late in the time window only benefits infants younger than 9 months. PMID- 20589709 TI - Adjuvant radiation therapy is associated with improved survival for adenoid cystic carcinoma of the breast. AB - BACKGROUND: The role of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast remains unclear. MATERIALS AND METHODS: We queried the Surveillance, Epidemiology, and End Results database for patients with breast ACC resected between 1988 and 2005, and divided patients based on the receipt of RT. Univariate and multivariate survival comparisons were made for overall and disease-specific survival. RESULTS: Three hundred seventy six patients met criteria for inclusion. Demographics and staging were similar between groups. Univariate analysis revealed an absolute overall and cause-specific survival benefit of 21% and 7% at 10 years (P = 0.005 and P = 0.12 respectively). In the multivariate analysis, RT was a significant predictor of overall and cause specific survival with hazard ratios of 0.44 (95% Confidence interval (CI) = 0.22 0.88) and 0.1 (95% CI: 0.01-0.88), respectively. CONCLUSIONS: RT after local surgical therapy for ACC of the breast improved both cause-specific and overall survival. Use of RT in this rare tumor should be considered in patients otherwise eligible for RT. PMID- 20589710 TI - Delphian node metastasis in head and neck cancers--oracle or myth? AB - Delphian node (DN) refers to the pre-laryngeal or pre-cricoid nodal tissue often identified during laryngeal or thyroid surgery. The original nomenclature is based on the assumption that metastasis to this node was predictive of aggressive disease and poor outcome for patients. In this article, we review the existing literature on the topic to determine the significance of DN metastasis in laryngeal, hypopharyngeal and thyroid cancers. PMID- 20589711 TI - Effects of preceding interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma. AB - BACKGROUND AND OBJECTIVES: Interferon (IFN) can eradicate hepatitis C virus (HCV) RNA from serum and hepatic tissue, and suppress the development of hepatocellular carcinoma (HCC). Despite such effectiveness, HCC develops even in HCV patients successfully treated with IFN therapy. METHODS: HCV-related HCC patients who underwent curative hepatectomy for HCC were divided into three groups according to preceding IFN for HCV infection therapy and the therapeutic effect: responders group (n = 23), non-responders group (n = 46), and no-IFN group (n = 215). Postoperative outcome was retrospectively examined in the three groups. RESULTS: AST and ALT were significantly lower in responders group than non-responders group (P < 0.001, P = 0.001) and no-IFN group (P = 0.001, P = 0.002). Platelet count was significantly higher in responders group than other groups (P = 0.008, P = 0.001). The percentage of cirrhotic patients in responders group was significantly lower than other groups (P = 0.017, P = 0.014). Multivariate analysis identified preceding IFN therapy to be associated with disease-free survival at marginal significance (P = 0.086), and as a significant independent factor for overall survival (P = 0.042). CONCLUSIONS: Preceding IFN therapy for HCV infection improves postoperative outcome in HCV-related HCC patients treated successfully with IFN. PMID- 20589712 TI - VEGF and cortactin expression are independent predictors of tumor recurrence following curative resection of gastric cancer. AB - INTRODUCTION: To investigate the clinicopathological role of expression of vascular endothelial growth factor (VEGF) and cortactin, as well as whether their expression are independent predictors of tumor recurrence following curative resection of gastric cancer. METHODS: One hundred twenty-eight patients with gastric cancer were included in this study. Formalin-fixed paraffin-embedded specimens were stained for VEGF and cortactin, and the correlation between the staining, clinicopathological parameters and prognostic power were analyzed. RESULTS: Of the 128 patients studied, 58 (45.3%) and 71 (55.5%) cases were strongly positive for VEGF and cortactin, respectively. VEGF expression correlated with Lauren classification (P < 0.001), pathological tumor stage (P < 0.001), and pathological tumor node metastasis (TNM) stage (P = 0.003). Cortactin expression correlated with pathological lymph node stage (P = 0.018), pathological TNM stage (P < 0.001), and degree of differentiation (P < 0.001). There were statistically significant associations between tumor recurrence and VEGF expression (P = 0.023), and cortactin expression (P < 0.001). In multivariate analysis, pathological TNM stage, VEGF expression, and cortactin expression were independent prognostic influence on disease-free survival (P < 0.001, 0.022, and 0.034, respectively). CONCLUSIONS: VEGF and cortactin may be a good biomarker to be applied in clinic to predict the prognosis of patients with curatively resected gastric cancer. PMID- 20589713 TI - More than maths and mindreading: sex differences in empathizing/systemizing covariance. AB - Empathizing-Systemizing theory posits a continuum of cognitive traits extending from autism into normal cognitive variation. Covariance data on empathizing and systemizing traits have alternately suggested inversely dependent, independent, and sex-dependent (one sex dependent, the other independent) structures. A total of 144 normal undergraduates (65 men, 79 women) completed the Reading the Mind in the Eyes, Embedded Figures, and Benton face recognition tests, the Autism Spectrum Quotient, and measures of digit length ratio and field of study; some also completed tests of motion coherence threshold (64) and go/no-go motor inhibition (128). Empathizing and systemizing traits were independent in women, but largely dependent in men. In men, level of systemizing skill required by field of study was directly related to social interactive and mindreading deficits; men's social impairments correlated with prolonged go/no-go response times, and men tended to apply systemizing strategies to solve problems of empathizing or global processing: rapid perceptual disembedding predicted heightened sensitivity to facial emotion. In women, level of systemizing in field was related to male-typical digit ratios and autistic superiorities in detail orientation, but not to autistic social and communicative impairments; and perceptual disembedding was related to social interactive skills but independent of facial emotion and visual motion perception. PMID- 20589714 TI - New strategies of pelvic nerves stimulation for recovery of pelvic visceral functions and locomotion in paraplegics. AB - AIMS: To present new strategies of pelvic nerves stimulation to enhance micturition, to control spasticity, and to recover locomotion in paraplegics. METHODS: Three consecutive patients-Th5, Th7, and Th10 spinal cord injured underwent laparoscopic transperitoneal implantation of octipolar electrodes to the sciatic and the pudendal nerves and one double extradural Brindley-Finetech electrode bilaterally to the sacral nerve roots S3 and S4. The two octipolar electrodes were connected to an implanted rechargeable generator, while the double Brindley electrode was connected to an implanted Brindley-Finetech receiver block. RESULTS: Continuous stimulation of the sciatic and pudendal nerves at a frequency of 20 Hz in all three patients permits complete control of the spasticity of the lower extremities and of reflex incontinence. Bladder emptying is obtained by sacral nerve roots stimulation alone in the first patient, by simple interruption of pudendal stimulation in the second ("pudendal deblockade") and by simultaneous sacral nerve roots stimulation with high frequency pudendal nerve blockade in the third patient. Functional electrical stimulation of the femoral nerves enables the Th4 paraplegics lower-limb cycling and the two further patients standing and alternative locomotion. CONCLUSION: This short series indicated that laparoscopic implantation of neuroprothesis to the pelvic nerves offers absolutely new strategies based on new combinations of various reported methods to enhance bladder functions and to recover some locomotion in paraplegics. PMID- 20589715 TI - Role for antibodies in altering behavior and movement. AB - At the past meeting of INSAR, the role of autoimmunity was discussed in an educational session. This article summarizes this discussion. In immune-mediated diseases, antibodies can contribute to the pathogenesis of the disease and are sometimes the force that drives the disease process. This concept has not been established for autism. In autoimmune diseases, such as systemic lupus erythematosus (SLE), antibodies are found to react with double-stranded DNA. These antibodies also cross-react with N-methyl-D aspartate receptors. Many SLE patients suffer neurologic syndromes of the central nervous system (CNS). Similarly individuals infected with Group A streptococcus (GAS) have antibodies against the GAS carbohydrate, which cross-react with tubulin and lysoganglioside GM1 on neurons. During the acute stage of infection, GAS-infected patients develop Syndenham chorea where the disease process is driven in part by these cross-reactive antibodies. As the antibody levels decrease, the clinical features of Syndenham chorea resolve. In these two immune-mediated diseases, antibodies clearly play a role in the pathogenesis of the diseases. There are reports that mothers of individuals with autism have antibodies that react with brain proteins and when these antibodies are passively transferred to pregnant non-human primates or rodents the offspring has behavioral and nervous system changes. It is still not clear whether the antibodies found in mothers of individuals with autism actually play a role in the disease. More studies need to be performed to identify the proteins recognized by the antibodies and to determine how these could affect development, behavior and changes within the CNS. PMID- 20589716 TI - Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedule (ADOS). AB - Restricted and repetitive behaviors (RRBs) observed during the Autism Diagnostic Observation Schedule [ADOS: Lord et al., 2000] were examined in a longitudinal data set of 455 toddlers and preschoolers (age 8-56 months) with clinical diagnosis of Autism Spectrum Disorders (ASD; autism, n=121 and pervasive developmental disorders-not otherwise specified (PDD-NOS), n=71), a nonspectrum disorder (NS; n=90), or typical development (TD; n=173). Even in the relatively brief semi-structured observations, GEE analyses of the severity and prevalence of RRBs differentiated children with ASD from those with NS and TD across all ages. RRB total scores on the ADOS were stable over time for children with ASD and NS; however, typically developing preschoolers showed lower RRB scores than typically developing toddlers. Nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children with PDD-NOS, NS, and TD than younger children under 2 years and those with autism. Item analyses revealed different relationships between individual items and NVIQ, age, diagnosis, and gender. These findings are discussed in terms of their implications for the etiology and treatment of RRBs as well as for the framework of ASD diagnostic criteria in future diagnostic systems. PMID- 20589717 TI - Overactive bladder: Is there a link to the metabolic syndrome in men? AB - It is becoming increasingly clear that a variety of metabolic, cardiovascular, and endocrine factors contribute to male pelvic health. In particular, a growing body of evidence suggests a relationship between lower urinary tract symptoms, benign prostatic hyperplasia, overactive bladder, erectile dysfunction, and the metabolic syndrome. This article explores these relationships, focusing on the role of the autonomic nervous system and hyperinsulinemia, together with their implications for urological practice. PMID- 20589718 TI - Kinematic analysis of overground locomotion in chicks incubated under different light conditions. AB - Domestic chicks walk within 3-4 hr after hatching following 21 days of incubation. However, differences in light exposure can vary incubation duration. Based on pilot studies, we predicted that there would be a positive relationship between incubation duration and locomotor competence at hatching. Embryos were incubated in one of three conditions that varied light duration and intensity, and overground locomotor performance was tested on the day of hatching. Chicks incubated in continuous bright light hatched 1-2 days earlier than chicks incubated in less or no light. Kinematic findings indicated that locomotor skill was similar across incubation conditions and led us to reject our hypothesis. We propose that light may accelerate locomotor development without adversely affecting skill. Our findings raise two important implications for future studies: whether light exposure accelerates locomotor circuit development; and/or it unmasks adaptive motor skill by accelerating development of other physiological systems. PMID- 20589720 TI - RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB MYH11 and AML1-ETO (RUNX1-RUNX1T1). AB - The core binding factor (CBF) acute myeloid leukemias (AMLs) are a prognostically distinct subgroup that includes patients with the inv(16) and t(8:21) chromosomal rearrangements. Both of these rearrangements result in the formation of fusion proteins, CBFB-MYH11 and AML1-ETO, respectively, that involve members of the CBF family of transcription factors. It has been proposed that both of these fusion proteins function primarily by dominantly repressing normal CBF transcription. However, recent reports have indicted that additional, CBF-repression independent activities may be equally important during leukemogenesis. This article will focus on these recent advances. PMID- 20589722 TI - AT-101 (R-(-)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model. AB - Prostate cancer remains a leading cause of cancer death in American men. Androgen deprivation therapy (ADT) is the most common treatment for advanced prostate cancer patients; however, ADT fails in nearly all cases resulting in castration resistant or androgen-insensitive (AI) disease. In many cases, this progression results from dysregulation of the pro-survival Bcl-2 family proteins. Inhibition of pro-survival Bcl-2 family proteins, therefore, may be an effective strategy to delay the onset of AI disease. Gossypol, a small molecule inhibitor of pro survival Bcl-2 family proteins, has been demonstrated to inhibit AI prostate cancer growth. The apoptotic effect of gossypol, however, has been demonstrated to be attenuated by the presence of androgen in a prostate cancer xenograft mouse model (Vertebral Cancer of Prostate [VCaP]) treated with AT-101 (R-(-)-gossypol acetic acid). This study was undertaken to better understand the in vitro effects of androgen receptor (AR) on AT-101-induced apoptosis. VCaP cells treated with AT 101 demonstrated an increase in apoptosis and downregulation of Bcl-2 pro survival proteins. Upon AR activation in combination with AT-101 treatment, apoptosis is reduced, cell survival increases, and caspase activation is attenuated. Akt and X inhibitor of apoptosis (XIAP) are downregulated in the presence of AT-101, and AR stimulation rescues protein expression. Combination treatment of bicalutamide and AT-101 increases apoptosis by reducing the expression of these pro-survival proteins. These data suggest that combination therapy of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer patients. PMID- 20589721 TI - Ganglioside GD1a suppression of NOS2 expression via ERK1 pathway in mouse osteosarcoma FBJ cells. AB - Inducible nitric oxide synthase (NOS2) is over-expressed in a number of tumors and implicated in tumor growth and metastasis. Murine FBJ osteosarcoma-derived FBJ-S1 cells are poorly metastatic and express the ganglioside GD1a, whereas highly metastatic FBJ-LL cells only slightly express this ganglioside. The present study demonstrates that NOS2 is more highly expressed in FBJ-LL cells compared to FBJ-S1 cells. By manipulating GM2/GD2 synthase expression or adding exogenous GD1a, GD1a inversely regulated NOS2 at the transcriptional level. GT1b suppressed NOS2 to the same extent as GD1a. Silencing NOS2 inhibited proliferation, migration, and anchorage-independent growth of FBJ-LL cells, suggesting that the metastatic properties of FBJ-LL cells are associated with NOS2. MEK1/2 inhibitor (U0126) increased NOS2 expression, whereas GD1a treatment decreased it. Co-treating the cells with GD1a and U0126 blocked the inhibition of NOS2 expression, suggesting that the GD1a signal is mediated by ERK1/2. NOS2 expression increased when ERK1, but not ERK2, was silenced, and GD1a did not suppress NOS2 expression in cells treated with another MEK1/2 inhibitor PD98059, suggesting that ERK1 phosphorylation is indispensable for the GD1a signal suppressing NOS2. PMID- 20589723 TI - A computational investigation of J couplings involving 27Al, 17O, and 31P. AB - Indirect nuclear spin-spin (J) couplings between (31)P, (27)Al, and (17)O are computed for Cl(3)POAlCl(3), Ph(3)PO, Ph(3)PAlCl(3), Al(H(2)O)(6)(3+), an aluminophosphate model system, and grossite model systems, using the B3LYP hybrid functional and the pcJ-n and aug-pcJ-n basis sets. The results provide computational corroboration of the existence of J coupling constants between (31)P, (17)O, and (27)Al of suitable magnitude for INEPT-style experiments in which connectivity is established as a result of magnetization transfer using these couplings. Potentially useful correlations between structure (bond lengths, angles, dihedrals) and the coupling constants (1)J((27)Al, (17)O), (1)J((31)P, (17)O), and (2)J((31)P, (27)Al) are presented. Calculated values of near zero for both (1)J((27)Al, (17)O) and (2)J((31)P, (27)Al), depending on the molecule and the geometry, suggest that some structurally important correlations could be absent in NMR spectra which rely on magnetization transfers solely based on these isotropic coupling constants. PMID- 20589724 TI - Study of liquid-liquid interfaces by an easily implemented localized NMR sequence. AB - To selectively extract heavy metals from solutions containing fission products, it is essential to optimize the liquid-liquid extraction processes. Such an objective requires improving the fundamental knowledge of the different mechanisms that are involved in these processes. In that respect, we propose a localized NMR sequence named LOCSY to assess the concentration profiles of different species involved in these processes. One of the goals of this sequence is to study the products as close as possible to the liquid-liquid interface with the help of a standard NMR spectrometer of chemistry labs. The one-dimensional spatial localization along the NMR tube is obtained by a discrete stepping of the frequency-selective excitation pulses under a pulsed field gradient. Specific data processing has been developed to obtain the 1D NMR spectra as a function of the vertical position in the NMR tube. The LOCSY sequence has been tested and evaluated on three different systems: (i) a cylindrical phantom inserted in the NMR tube containing 4-methylsalicylic acid solution, (ii) D(2)O/olive oil biphasic system, and (iii) the dissolution of solid saccharose in D(2)O. These examples illustrate potential applications of the LOCSY sequence, particularly the possibility to measure concentration profiles and to study phenomena such as diffusion, provided the dynamic range is compatible with NMR timescale and sensitivity. PMID- 20589725 TI - GIAO DFT 13C/15N chemical shifts in regioisomeric structure determination of fused pyrazoles. AB - The combined use of two-dimensional NMR correlation experiments and gauge including atomic orbital density functional theory in (13)C NMR chemical shift (CS) calculations allowed reliable and simple structural determination of regioisomeric heterocyclic systems that originate from the reactions of acylquinolinones with substituted hydrazines. Moreover, the results of differential analysis between the calculated (15)N NMR CSs for hypothetical structures and the experimental data of the title azaheterocyclic systems were even more advantageous with respect to (13)C because there was no need for correlational analysis: structures of the regioisomeric compounds could be determined just by direct comparison. PMID- 20589726 TI - Synthesis and complete assignment of the 1H and 13C NMR signals of new acetamido and aminoflavonoid derivatives. AB - The complete (1)H and (13)C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamidoflavonols and 9 aminoflavonols has been performed using one- and two-dimensional NMR techniques including COSY, HMQC and HMBC experiments. PMID- 20589727 TI - Differentiation between [1,2,4]triazolo[1,5-a] pyrimidine and [1,2,4]triazolo[4,3 a]-pyrimidine regioisomers by 1H-15N HMBC experiments. AB - The condensation of malonoaldehyde derivatives with either a 3-amino-[1,2,4] triazole or a 3,5-diamino-[1,2,4]-triazole precursor was studied. In agreement with previous reports, two different bicycles, namely, bearing the regioisomeric [1,2,4]triazolo[1,5-a]pyrimidine (1) or [1,2,4]triazolo[4,3-a]pyrimidine (2) structural surrogates, could be obtained. We found that, depending on the triazole precursor, only one regioisomer resulted, either of the 1 or 2 series. We also observed that these two structural surrogates could be unambiguously differentiated by indirectly measuring their (15)N chemical shifts by (1)H-(15)N HMBC experiments. The occasional conversion of [1,2,4]triazolo[4,3-a]pyrimidines to the [1,2,4]triazolo[1,5-a]pyrimidine counterparts could be unequivocally determined by (15)N NMR data. PMID- 20589728 TI - New perspectives in the PAW/GIPAW approach: J(P-O-Si) coupling constants, antisymmetric parts of shift tensors and NQR predictions. AB - In 2001, Pickard and Mauri implemented the gauge including projected augmented wave (GIPAW) protocol for first-principles calculations of NMR parameters using periodic boundary conditions (chemical shift anisotropy and electric field gradient tensors). In this paper, three potentially interesting perspectives in connection with PAW/GIPAW in solid-state NMR and pure nuclear quadrupole resonance (NQR) are presented: (i) the calculation of J coupling tensors in inorganic solids; (ii) the calculation of the antisymmetric part of chemical shift tensors and (iii) the prediction of (14)N and (35)Cl pure NQR resonances including dynamics. We believe that these topics should open new insights in the combination of GIPAW, NMR/NQR crystallography, temperature effects and dynamics. Points (i), (ii) and (iii) will be illustrated by selected examples: (i) chemical shift tensors and heteronuclear (2)J(P-O-Si) coupling constants in the case of silicophosphates and calcium phosphates [Si(5)O(PO(4))(6), SiP(2)O(7) polymorphs and alpha-Ca(PO(3))(2)]; (ii) antisymmetric chemical shift tensors in cyclopropene derivatives, C(3)X(4) (X = H, Cl, F) and (iii) (14)N and (35)Cl NQR predictions in the case of RDX (C(3)H(6)N(6)O(6)), beta-HMX (C(4)H(8)N(8)O(8)), alpha-NTO (C(2)H(2)N(4)O(3)) and AlOPCl(6). RDX, beta-HMX and alpha-NTO are explosive compounds. PMID- 20589729 TI - NMR investigation of guest-host complex between chloroform and cryptophane C. AB - Guest-host complex between cryptophane C, possessing two non-equivalent caps, and chloroform is investigated by NMR spectroscopy. The kinetics of the chloroform exchange between the bound and free sites is determined by (1)H exchange spectroscopy. Moreover, the preferential orientation of chloroform molecule with respect to the cryptophane C frame is examined by the NOESY and ROESY experiments. The experimental findings are compared to the results of quantum chemical calculations. PMID- 20589730 TI - A simple methodology for the determination of fatty acid composition in edible oils through 1H NMR spectroscopy. AB - A simple methodology for the determination of the fatty acid composition of edible oils through (1)H NMR is proposed. The method is based on the fact that all fatty acid chains are esterified to a common moiety, glycerol, and the quantification is done directly in the (1)H NMR spectra through the relationship between the areas of a characteristic signal of each fatty acid and a signal of the glycerol moiety, without the use of mathematical equations. The methodology was successfully applied to determine the fatty acid composition of several edible oils, with equivalent results to those given by the AOAC Official method by gas chromatography. Its main advantages are simplicity and the lack of need for sample pre-treatment such as derivatization or extraction. PMID- 20589731 TI - Computation and NMR crystallography of terbutaline sulfate. AB - This article addresses, by means of computation and advanced experiments, one of the key challenges of NMR crystallography, namely the assignment of individual resonances to specific sites in a crystal structure. Moreover, it shows how NMR can be used for crystal structure validation. The case examined is form B of terbutaline sulfate. CPMAS (13)C and fast MAS (1)H spectra have been recorded and the peaks assigned as far as possible. Comparison of (13)C chemical shifts computed using the CASTEP program (incorporating the Gauge Including Projector Augmented Wave principle) with those obtained experimentally enable the accuracy of the two distinct single-crystal evaluations of the structure to be compared and an error in one of these is located. The computations have substantially aided in the assignments of both (13)C and (1)H resonances, as has a series of two-dimensional (2D) spectra (HETCOR, DQ-CRAMPS and proton-proton spin diffusion). The 2D spectra have enabled many of the proton chemical shifts to be pinpointed. The relationships of the NMR shifts to the specific nuclear sites in the crystal structure have therefore been established for most (13)C peaks and for some (1)H signals. Emphasis is placed on the effects of hydrogen bonding on the proton chemical shifts. PMID- 20589732 TI - Problems, artifacts and solutions in the INADEQUATE NMR experiment. AB - The INADEQUATE experiment can provide unequalled, detailed information about the carbon skeleton of an organic molecule. However, it also has the reputation of requiring unreasonable amounts of sample. Modern spectrometers and probes have mitigated this problem, and it is now possible to get good structural data on a few milligrams of a typical organic small molecule. In this paper, we analyze the experiment step by step in some detail, to show how each part of the sequence can both contribute to maximum overall sensitivity and can lead to artifacts. We illustrate these methods on three molecules: 1-octanol, the steroid 17alpha ethynylestradiol and the isoquinoline alkaloid beta-hydrastine. In particular, we show that not only is the standard experiment powerful, but also a version tuned to small couplings can contribute vital structural information on long-range connectivities. If the delay in the spin echo is long, pairs of carbons with small couplings can create significant double-quantum coherence and show correlations in the spectrum. These are two- and three-bond correlations in a carbon chain or through a heteroatom in the molecule. All these mean that INADEQUATE can play a viable and important role in routine organic structure determination. PMID- 20589733 TI - Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2 diabetic patients. AB - Type 2 diabetes (T2D) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products. Since reactive oxygen species (ROS) can cause damage to biological macromolecules including DNA, this study investigated oxidative damage to DNA using the alkaline (pH > 13) comet assay in peripheral whole blood leukocytes sampled from 15 dyslipidemic T2D patients treated with simvastatin (20 mg/day), 15 dyslipidemic T2D patients not treated with simvastatin, 20 non-dyslipidemic T2D patients, and 20 healthy individuals (controls). Our results showed a greater DNA migration in terms of damage index (DI) (p < 0.01) in the dyslipidemic T2D patients not treated with statin (DI = 67.70 +/- 10.89) when compared to the dyslipidemic T2D patients under statin treatment (DI = 47.56 +/- 7.02), non-dyslipidemic T2D patients (DI = 52.25 +/- 9.14), and controls (DI = 13.20 +/- 6.40). Plasma malondialdehyde (MDA) and C-reactive protein (CRP) levels were also increased and total antioxidant reactivity (TAR) and paraoxonase activity (PON1) decreased in non-dyslipidemic T2D patients and dyslipidemic T2D non-treated with simvastatin. We also found that DI was inversely correlated with TAR (r = -0.61, p < 0.05) and PON1 (r = -0.67, p < 0.01). In addition, there was a significant positive correlation between DI and CRP (r = 0.80, p < 0.01). Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients. PMID- 20589734 TI - In vitro effects of 2-methoxyestradiol-bis-sulphamate on the non-tumorigenic MCF 12A cell line. AB - A priority in recent anti-cancer drug development has been attaining better side effect profiles for potential compounds. To produce highly specific cancer therapies it is necessary to understand both the effects of the proposed compound on cancer and on normal cells comprising the rest of the human body. Thus in vitro evaluation of these compounds against non-carcinogenic cell lines is of critical importance. One of the most recent developments in experimental anti cancer agents is 2-methoxyestradiol-bis-sulphamate (2ME-BM), a sulphamoylated derivative of 2-methoxyestradiol. The aim of this study was to evaluate the in vitro effects of 2ME-BM on cell proliferation, morphology and mechanisms of cell death in the non-carcinogenic MCF-12A breast epithelial cell line. The study revealed changes in proliferative capacity, morphology and cell death induction in response to 2ME-BM exposure (24 h at 0.4 microM). Microscopy showed decreased cell density and cell death-associated morphology (increased apoptotic characteristics), a slight increase in acidic intracellular vesicles and insignificant ultra-structural aberrations. Mitotic indices revealed a G(2)M phase cell cycle block. This was confirmed by flow cytometry, where an increased fraction of abnormal cells and a decrease in cyclin B1 levels were observed. These results evidently demonstrate that the non-carcinogenic MCF-12A cell line is less susceptible when compared to 2ME-BM-exposed cancer cell lines previously tested. Further in vitro research into the mechanism of this potentially useful compound is warranted. PMID- 20589735 TI - Testosterone suppresses oxidative stress in human neutrophils. AB - The in vitro effect of testosterone on human neutrophil function was investigated. Blood neutrophils from healthy male subjects were isolated and treated with 10 nM, 0.1 and 10 microM testosterone for 24 h. As compared with untreated cells, the testosterone treatment produced a significant decrease of superoxide production as indicated by the measurement of extra- and intracellular superoxide content. An increment in the production of nitric oxide was observed at 0.1 and 10 microM testosterone concentrations, whereas no effect was found for 10 nM. Intracellular calcium mobilization was significantly increased at 10 nM, whereas it was reduced at 10 microM testosterone. There was an increase in phagocytic capacity at 10 nM and a decrease of microbicidal activity in neutrophils treated with testosterone at 10 microM. Glutathione reductase activity was increased by testosterone treatment, whereas no effect was observed in other antioxidant enzyme activities. An increase in the content of thiol groups was observed at all testosterone concentrations. Lipid peroxidation in neutrophils evaluated by levels of TBARS was decreased at 10 nM and 0.1 microM testosterone. These results indicate the antioxidant properties of testosterone in neutrophils as suggested by reduction of superoxide anion production, and lipid peroxidation, and by the increase in nitric oxide production, glutathione reductase activity and the content of thiol groups. Therefore, the plasma levels of testosterone are important regulators of neutrophil function and so of the inflammatory response. PMID- 20589736 TI - Muscle origin of porcine satellite cells affects in vitro differentiation potential. AB - Post-natal muscle regeneration relies on the activation of tissue stem cells known as satellite cells, to repair damage following exercise trauma and disease. Satellite cells from individual muscles are known to be heterogeneous with regard to proliferation, fusion and transplantation abilities, although the muscle origin has rarely been considered pertinent to their differentiation capabilities. In this study we compared the potential of two functionally distinct skeletal muscle satellite cell populations from porcine diaphragm and hind-limb semi-membranosus muscles. These two muscles were chosen primarily for differences in metabolic and contractile properties: the diaphragm is more continuously active and has a greater oxidative capacity. Cells were induced to differentiate towards myogenic and adipogenic lineages, and here we have shown that cells from diaphragm exhibit a significantly greater degree of myogenesis compared with those from semi-membranosus, while the converse was true for adipogenesis. Unexpectedly, both conditions generated small numbers of cells with neuronal characteristics for both muscle types, although more so in cells derived from the diaphragm. With increased interest in muscle adiposity with age and disease, these findings suggest that muscle origin of satellite cells does affect lineage fate, however whether differences in developmental origin or metabolic activity of the parent tissue govern this, remains to be determined. PMID- 20589737 TI - Mitochondrial dynamics and its responds to proteasome defection during Picea wilsonii pollen tube development. AB - Tip growth of pollen tubes is essential for higher plant sexual reproduction and has been proposed to be highly regulated by the ubiquitin/proteasome pathway (UPP). The dynamics of mitochondria and the functions of the UPP on mitochondrial dynamics during pollen tube development are still poorly understood. In the present study, using real-time laser scanning and transmission electron microscope, it was revealed that mitochondria in Picea wilsonii, are either ellipsoid or filamentous with various lengths. Time-lapse images indicated that the two forms of mitochondria interconvert frequently through opposite process of fusion and fission. Examination of mitochondrial morphology during four key stages of in vitro pollen tube development revealed a link between mitochondrial remodeling and the process of pollen tube elongation. We also report that MG132, a specific proteasome inhibitor, not only strongly disturbed the mitochondrial remodeling but also significantly reduced mitochondrial membrane potential during pollen tube development. This finding provides new insight into the function of the proteasome in tip growth of pollen tubes. PMID- 20589738 TI - The JNK pathway modulates expression and phosphorylation of 4E-BP1 in MIN6 pancreatic beta-cells under oxidative stress conditions. AB - Stress-mediated apoptosis may play a crucial role in loss of pancreatic beta-cell mass, contributing to the development of diabetes. We have recently identified that translational control involving the translational suppressor eIF4E binding protein-1 (4E-BP1) which is important for beta-cell survival under endoplasmic reticulum (ER) stress. The Eif4ebp1 gene, encoding 4E-BP1, is a direct target of a transcription factor activating transcription factor-4 (ATF4), a master regulator of gene expression in stress responses. In the current study, we investigated 4E-BP1 expression in mouse insulinoma line 6 (MIN6) cells treated with arsenite, an inducer of oxidative stress which is another contributor of beta-cell loss. We found that arsenite-induced 4E-BP1 expression level was lower than that induced by thapsigargin, an ER stress inducer, although ATF4 was similarly induced by these agents. The ratio of the dephosphorylated form of 4E BP1, which has the highest activity, to phosphorylated forms was, however, greater in MIN6 cells treated with arsenite as compared to that in thapsigargin treated cells. Arsenite-induced 4E-BP1 mRNA and protein expressions were augmented by simultaneous treatment with a c-Jun N-terminal kinase (JNK) specific inhibitor, SP600125. The agent also suppressed the level of the dephosphrylated form of 4E-BP1 in arsenite-treated MIN6 cells. Thus, JNK activated by oxidative stress is involved in the modulation of 4E-BP1 expression and phosphorylation in MIN6 cells, which may contribute to fine tuning of translational control under stress conditions. PMID- 20589739 TI - Melatonin attenuates methotrexate-induced oxidative stress and renal damage in rats. AB - Nephrotoxicity is an adverse side effect of methotrexate (MTX) chemotherapy. The present study verifies whether melatonin, an endogenous antioxidant prevents MTX induced renal damage. Adult rats were administered 7 mg/kg body weight MTX intraperitoneally for 3 days. In the melatonin pretreated rats, 40 mg/ kg body weight melatonin was administered daily intraperitoneally 1 h before the administration of MTX. The rats were killed 12 h after the final dose of MTX/vehicle. The kidneys were used for light microscopic and biochemical studies. The markers of oxidative stress were measured along with the activities of the antioxidant enzymes and myeloperoxidase activity in the kidney homogenates. Pretreatment with melatonin reduced MTX induced renal damage both histologically and biochemically as revealed by normal plasma creatinine levels. Melatonin pretreatment reduced MTX induced oxidative stress, alteration in the activity of antioxidant enzymes as well as elevation in myeloperoxidase activity. The results suggest that melatonin has the potential to reduce MTX induced oxidative stress, neutrophil infiltration as well as renal damage. As melatonin is an endogenous antioxidant and is non-toxic even in high doses it is suggested that melatonin may be beneficial in minimizing MTX induced renal damage in humans. PMID- 20589740 TI - Protegrin-1 orientation and physicochemical properties in membrane bilayers studied by potential of mean force calculations. AB - Protegrin-1 (PG-1) belongs to the family of antimicrobial peptides. It interacts specifically with the membrane of a pathogen and kills the pathogen by releasing its cellular contents. To fully understand the energetics governing the orientation of PG-1 in different membrane environments and its effects on the physicochemical properties of the peptide and membrane bilayers, we have performed the potential of mean force (PMF) calculations as a function of its tilt angle at four distinct rotation angles in explicit membranes composed of either DLPC (1,2-dilauroylphosphatidylcholine) or POPC (1-palmitoyl-2 oleoylphosphatidylcholine) lipid molecules. The resulting PMFs in explicit lipid bilayers were then used to search for the optimal hydrophobic thickness of the EEF1/IMM1 implicit membrane model in which a two-dimensional PMF in the tilt and rotation space was calculated. The PMFs in explicit membrane systems clearly reveal that the energetically favorable tilt angle is affected by both the membrane hydrophobic thickness and the PG-1 rotation angle. Local thinning of the membrane around PG-1 is observed upon PG-1 tilting. The thinning is caused by both hydrophobic mismatch and arginine-lipid head group interactions. The two dimensional PMF in the implicit membrane is in good accordance with those from the explicit membrane simulations. The ensemble-averaged Val16 (15)N and (13)CO chemical shifts weighted by the two-dimensional PMF agree fairly well with the experimental values, suggesting the importance of peptide dynamics in calculating such ensemble properties for direct comparison with experimental observables. PMID- 20589741 TI - Evaluating the possible genotoxic, mutagenic and tumor cell proliferation inhibition effects of a non-anticoagulant, but antithrombotic algal heterofucan. AB - Fucan is a term used to denominate a family of sulfated polysaccharides rich in L fucose. They are extracted mainly from brown seaweeds and echinoderms. The brown seaweed Spatoglossum schroederi (Dictyotaceae) synthesizes three heterofucans named A, B and C. Our research group purified a non-anticoagulant heterofucan (fucan A) which displays antithrombotic activity in vivo. However, its in vitro toxicity has yet to be determined. This work presents the evaluation of the potential cytotoxicity, mutagenicity and genotoxicity of this fucan. After 48 h incubation fucan A cytotoxicity was determinate using MTT assay. Tumor-cell (HeLa, PC3, PANC, HL60) proliferation was inhibited 2.0-43.7%; at 0.05-1 mg ml-1 of the heterofucan, the 3T3 non-tumor cell line proliferation was also inhibited (3.3-22.0%). On the other hand, the CHO tumorigenic and RAW non-tumor cell lines proliferation were not affected by this molecule (0.05-1 mg ml-1). We observed no mutagenic activity in Salmonella reversion assay when bacterial strains TA97a, TA98, TA100 and TA102 (with and without S9) were used.Comet assay showed that fucan A had no genotoxic effect (from 20 to 1000 mg ml-1) on CHO cells. In conclusion, this study indicates that the S. schroederi fucan A was not found to be genotoxic or mutagenic compound; thus it could be used in new antithrombotic drug development. PMID- 20589742 TI - Transcriptional response of hepatic largemouth bass (Micropterus salmoides) mRNA upon exposure to environmental contaminants. AB - Microarrays enable gene transcript expression changes in near-whole genomes to be assessed in response to environmental stimuli. We utilized oligonucleotide microarrays and subsequent gene set enrichment analysis (GSEA) to assess patterns of gene expression changes in male largemouth bass (Micropterus salmoides) hepatic tissues after a 96 h exposure to common environmental contaminants. Fish were exposed to atrazine, cadmium chloride, PCB 126, phenanthrene and toxaphene via intraperitoneal injection with target body burdens of 3.0, 0.00067, 2.5, 50 and 100 ug g(-1), respectively. This was conducted in an effort to identify potential biomarkers of exposure. The expressions of 4, 126, 118, 137 and 58 mRNA transcripts were significantly (P <= 0.001, fold change >=2*) affected by exposure to atrazine, cadmium chloride, PCB 126, phenanthrene and toxaphene exposures, respectively. GSEA revealed that none, four, five, five and three biological function gene ontology categories were significantly influenced by exposure to these chemicals, respectively. We observed that cadmium chloride elicited ethanol metabolism responses, and along with PCB 126 and phenanthrene affected transcripts associated with protein biosynthesis. PCB 126, phenanthrene and toxaphene also influenced one-carbon compound metabolism while PCB 126 and phenanthrene affected mRNA transcription and mRNA export from the nucleus and may have induced an antiestrogenic response. Atrazine was found to alter the expression of few hepatic transcripts. This work has highlighted several biological processes of interest that may be helpful in the development of gene transcript biomarkers of chemical exposure in fish. PMID- 20589743 TI - Inhibitory effect of MIL glycoprotein on expression of pro-inflammatory mediators in carbon tetrachloride-induced mice liver damage. AB - The aim of the present study was to evaluate immunomodulatory and hepatoprotective effects of glycoprotein isolated from Morus indica Linne (MIL glycoprotein) on carbon tetrachloride (CCl(4) )-induced liver injury. In the present study, MIL glycoprotein (5 and 10 mg kg(-1) body weight) was administered to ICR mice for 7 days prior to CCl(4) treatment. We evaluated the activities of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARS), and expression of inflammation-related mediators including cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta in CCl(4) -treated mice. Our results revealed that MIL glycoprotein reduced the activities of ALT, LDH and TBARS in serum from CCl(4) -treated mice. We also found that MIL glycoprotein reduced the activity of COX-2 and expression of TNF-alpha and IL-1 beta in liver from CCl(4) -treated mice. Moreover, administration of MIL glycoprotein suppressed on stress-activated protein kinase/c-jun N-terminal kinase phosphorylation and activator protein-1 transcriptional activation in livers from CCl(4) -treated mice. The results from these experiments indicate that MIL glycoprotein effectively protects against liver injury, mainly through downregulation of oxidative stress and the inflammatory response. In conclusion, we suggest that the MIL glycoprotein might be one component of health supplements for prevention of liver diseases. PMID- 20589744 TI - Overview of the nonclinical quality and toxicology testing for recombinant biopharmaceuticals produced in mammalian cells. AB - Biopharmaceuticals represent significant advances in therapeutic approaches for unmet medical needs, and increasingly, traditional pharmaceutical firms have been incorporating biotechnology capabilities into their product portfolios. There are some differences in the overall safety testing paradigms for small molecules and biopharmaceuticals, this safety testing including both quality and toxicology aspects. These differences are associated with both the manufacturing processes involved and the molecules themselves. For example, for biopharmaceuticals, living cells represent the factories for synthesizing complex molecular entities. As a result of this, safety testing for this class of drugs includes adventitious agent testing (e.g. viral, mycoplasma, transmissible spongiform encephalopathy agents) not normally needed for small molecules. Also, strategies for nonclinical toxicology testing of biopharmaceuticals differ from the paradigms used for small molecules and often need to be defined on a case-by-case basis, primarily taking into consideration species cross-reactivity attributes of the molecule of interest. Certain studies required for small molecules are not applicable to most biopharmaceuticals (i.e. genotoxicity testing, testing for interactions with the hERG channel). This manuscript provides an overview of both the quality and nonclinical toxicology testing for these mammalian-cell-derived products, two elements pivotal to the overall nonclinical assessment of the safety of these biopharmaceutical products. PMID- 20589746 TI - Antioxidant activity and phenolic content of wine vinegars produced by two different techniques. AB - BACKGROUND: The presence of phenolics in fruit, red wine and vinegar has positive health effects due to their significant antioxidant activity. The aim of the study was to determine the effects of two different vinegar production methods on antioxidant activity and phenolic level of vinegars derived from Ulugbey Karasi grapes. Traditional surface and industrial submerge methods were used to make vinegar. Samples were taken from fresh red grape juice, maceration, wine, traditional vinegar and industrial vinegar. RESULTS: Total phenolic content of traditional and industrial vinegar samples were 2690 mg L(-1) and 2461 mg L(-1) GAE, respectively. ORAC values of traditional and industrial vinegar samples were 10.50 micromol mL(-1)and 8.84 micromol mL(-1) TE, respectively. Antioxidant activity values of traditional and industrial vinegars were 13.50 mmol L(-1) and 10.37 mmol L(-1) TEAC, respectively. Gallic acid, catechin, epicatechin, chlorogenic acid, caffeic acid, syringic acid, p-coumaric acid and ferulic acid were detected in grape juice, wine and vinegar samples. The content of catechin in industrial vinegar (27.50 mg L(-1)) was significantly higher than that of in traditional vinegar (13.76 mg L(-1)) (P < 0.05). Traditional vinegar had higher amounts of chlorogenic and syringic acids than the industrial vinegar (P > 0.05). CONCLUSION: Results of this study showed that different production methods affected the functional constituents of wine vinegars. PMID- 20589747 TI - The langmuir-blodgett approach to making colloidal photonic crystals from silica spheres. AB - The area of colloidal photonic crystal research has attracted enormous attention in recent years as a result of the potential of such materials to provide the means of fabricating new or improved photonic devices. As an area where chemistry still predominates over engineering the field is still in its infancy in terms of finding real applications being limited by ease of fabrication, reproducibility and 'quality'- for example the extent to which ordered structures may be prepared over large areas. It is our contention that the Langmuir-Blodgett assembly method when applied to colloidal particles of silica and perhaps other materials, offers a way of overcoming these issues. To this end the assembly of silica and other particles into colloidal photonic crystals using the Langmuir-Blodgett (LB) method is described and some of the numerous papers on this topic, which have been published, are reviewed. It is shown that the layer-by-layer control of photonic crystal growth afforded by the LB method allows for the fabrication of a range of novel, layered photonic crystals that may not be easily assembled using any other approach. Some of the more interesting of these structures, including so-called heterostructured photonic crystals comprising of layers of spheres having different diameters are presented and their optical properties described. Finally, we offer our comments as to future applications of this interesting technology. PMID- 20589745 TI - Manganese modulation of MAPK pathways: effects on upstream mitogen activated protein kinase kinases and mitogen activated kinase phosphatase-1 in microglial cells. AB - Multiple studies demonstrate that manganese (Mn) exposure potentiates inflammatory mediator output from activated glia; this increased output is associated with enhanced mitogen activated protein kinase (MAPK: p38, ERK and JNK) activity. We hypothesized that Mn activates MAPK by activating the kinases upstream of MAPK, i.e. MKK-3/6, MKK-1/2 and MKK-4 (responsible for activation of p38, ERK, and JNK, respectively), and/or by inhibiting a major phosphatase responsible for MAPK inactivation, MKP-1. Exposure of N9 microglia to Mn (250 um), LPS (100 ng ml-1) or Mn + LPS increased MKK-3/6 and MKK-4 activity at 1 h; the effect of Mn + LPS on MKK-4 activation was greater than the rest. At 4 h, Mn, LPS, and Mn + LPS increased MKK-3/6 and MKK-1/2 phosphorylation, whereas MKK-4 was activated only by Mn and Mn + LPS. Besides activating MKK-4 via Ser257/Thr261 phosphorylation, Mn (4 h) prevented MKK-4's phosphorylation on Ser80, which negatively regulates MKK-4 activity. Exposure to Mn or Mn + LPS (1 h) decreased both mRNA and protein expression of MKP-1, the negative MAPK regulator. In addition, we observed that at 4 h, but not at 1 h, a time point coinciding with increased MAPK activity, Mn + LPS markedly increased TNF-alpha, IL-6 and Cox-2 mRNA, suggesting a delayed effect. The fact that all three major groups of MKKs, MKK-1/2, MKK-3/6 and MKK-4, are activated by Mn suggests that Mn-induced activation of MAPK occurs via traditional mechanisms, which perhaps involve the MAPKs furthest upstream, MKKKs (MAP3Ks). In addition, for all MKKs, Mn-induced activation was persistent at least for 4 h, indicating a long-term effect. PMID- 20589748 TI - Baseline PSA as a predictor of prostate cancer-specific mortality over the past 2 decades: Duke University experience. AB - BACKGROUND: A diagnosis of prostate cancer is not often predictive of death from prostate cancer because of competing causes of mortality. Identification of the risk of death from prostate cancer and death from all causes using information available at the time of baseline prostate-specific antigen (PSA) measurement appears to be particularly pertinent. METHODS: The Duke Prostate Center database was used to identify men who had their PSA level measured over the past 20 years. The Cox proportional hazards model was used to assess whether baseline PSA, race, and age at baseline PSA could predict death from prostate cancer and death from all causes after baseline PSA measurement. The receiver operating characteristic (ROC) curve was performed to analyze the accuracy of baseline PSA as a continuous variable in predicting death from prostate cancer. RESULTS: A total of 4568 men diagnosed with prostate cancer after baseline PSA measurement were included. On multivariate analysis, baseline PSA levels of 4.0 to 9.9 ng/mL and >=10 ng/mL were associated with significantly higher rates of death from prostate cancer compared with PSA levels <2.5 ng/mL. An advanced age at baseline PSA and African American race were associated with a higher death rate from prostate cancer and death from all causes. The area under the ROC curve for baseline PSA predicting death was 0.839. When a baseline PSA of 10 ng/mL was chosen to predict death from prostate cancer, the corresponding sensitivity and specificity were 77% and of 78%, respectively. CONCLUSIONS: Baseline PSA appears to be a reliable and independent predictor of death from prostate cancer. A baseline PSA of >=4 ng/mL has been associated with higher risk of death from prostate cancer. PMID- 20589749 TI - Prospective collection of tissue samples at autopsy in children with diffuse intrinsic pontine glioma. AB - BACKGROUND: Brain tissue obtained at autopsy has been used in research for non oncologic disorders. However, to the best of the authors' knowledge, this tool has never been systematically used in large investigational studies for cancer. A prospective, multicenter study was conducted to assess the feasibility of tissue collection at autopsy and its suitability for molecular analyses in children with diffuse intrinsic pontine glioma. METHODS: Tumor tissue was collected at the time of diagnosis, if clinically indicated, or at autopsy. Normal brain tissue was also collected at autopsy. The integrity of DNA and RNA was evaluated in all samples. Logistic data regarding autopsies were recorded. The feasibility of tissue collection at autopsy was assessed for patients treated at a single institution over a 43-month period. RESULTS: Tumor samples were collected at the time of diagnosis (n = 3) or at autopsy (n = 38) at 29 centers across the United States; samples were obtained at diagnosis and autopsy in 2 cases. The median interval from death to autopsy was 7.7 hours. DNA and RNA with minimal or partial degradation, which were suitable for genome-wide analysis, were obtained from 100% and 63% of tumor samples, respectively. At the coordinating institution, approximately 40% of parents consented to autopsy and 40% declined. During the study period, 12 autopsies were performed on patients who did not receive therapy at the coordinating center. CONCLUSIONS: Multicenter, biological studies based on tissue obtained at autopsy appear to be feasible in children with brain cancer. The current experience established a new paradigm for brain tissue collection, which may increase the potential for research studies in patients with cancer. PMID- 20589750 TI - Drug delivery trends in clinical trials and translational medicine: evaluation of pharmacokinetic properties in special populations. AB - In spite of the recent advances in technology to optimize the absorption, distribution, metabolism and elimination (ADME) properties of new and promising medicinal products to reduce clinical failures, the investigation of drug disposition in the pediatric and elderly populations continues to be under evaluated. With the increasing prevalence of aging populations world-wide, there is a growing concern from health care providers, regulators and the general public that drug delivery is still less than optimal for the vulnerable patient populations likely to be more sensitive to adverse effects of the new investigational drugs. This review of the ClinicalTrials.gov database revealed a rapidly increasing number of clinical trials and a trend towards wider inclusion criteria of the elderly population in clinical trials over the past 10 years. However, when we summarized trials by drug delivery, biological platforms, and disease categories, less than 10% of these trials included pharmacokinetic evaluation in elderly subjects greater than 65 years of age, and less than 4% included pharmacokinetic evaluation in children less than 17 years of age. Across the various disease areas, the percentage of trials that included pharmacokinetic evaluation in the children and elderly has remained low and is consistently less than the studies that included the younger 18 to 65 age group. Therefore, it is not known whether the right information is being generated from the growing number of clinical trials to guide optimal dosing recommendations in special patient populations. PMID- 20589751 TI - Perfectionism and eating behaviour in Portuguese adolescents. AB - OBJECTIVES: The main objective was to investigate the association between perfectionism and eating behaviour in a non-clinical sample of adolescents of both genders. METHOD: 997 middle and high school students completed the Portuguese versions of the child-adolescent perfectionism scale (CAPS) and of the eating attitudes test -25 (EAT-25). RESULTS: In both genders, the perfectionism total score and the sociallyprescribed perfectionism (SPP) score were positive and significantly correlated with the EAT total score and with all EAT dimensions: Drive for Thinness (DT), Bulimic Related Behaviour (BRB), Social Pressure to Eat (SPE). In girls, self-oriented perfectionism (SOP) was also associated with the EAT total score and its dimensions, whereas in boys it was only associated with EAT total score and DT. In both genders SPP was a useful predictor of the EAT-25 total score and of all its dimensions. In which respects SOP, there were some gender differences showing that in boys this dimension should not be considered a predictor of eating behaviours. CONCLUSION: These results confirm that high levels of perfectionism (SOP and SPP) are associated with abnormal eating behaviour in both genders. PMID- 20589752 TI - Getting better? PMID- 20589753 TI - Making eating disorders classification work in ICD-11. AB - The time has come again for the revision of the existing classifications systems and the creation of new versions, DSM-V and ICD-11. In September 2009, an initial call for comments and views regarding the development of the ICD-11 was made to the Eating Disorders Section of the Royal College of Psychiatry. This Viewpoint summarises the main points collected from child and adolescents and eating disorder (ED) psychiatrists in response to this consultation, outlines some proposals for modification of the relevant section(s) of ICD-11 and gives our views. PMID- 20589754 TI - p53 control of bone remodeling. AB - Tumor suppressor p53 is a transcription regulator that displays anti proliferation activities once activated by stress, in particular genotoxic stress. Recent mouse genetic studies revealed a critical role for p53 in bone remodeling, supported by both loss-of-function and gain-of function studies. p53 deficiency concurrently enhances proliferation and accelerates differentiation in mesenchymal stem cells and osteoprogenitor cells, resulting in an increase in bone formation and bone mass/density. Moreover, Atm, c-Abl, and Mdm2, upstream regulators of p53 in DNA damage response, regulate osteoblast differentiation and bone remodeling as well. While the molecular mechanisms await further investigation, there is evidence to suggest that p53 regulate osteoblast differentiation via transcription factors Runx2/Osterix, which are involved in osteoblast differentiation and transformation and are under the control of BMP and IGF pathways. Moreover, there are studies showing that p53 inhibits cell differentiation in many other tissues. These findings suggest that p53 acts as a safeguard of differentiation in addition to "guardian of the genome" and challenge the conventional wisdom that tumor suppressors usually block cell proliferation and promote differentiation. PMID- 20589755 TI - Embryonic stem cell neurogenesis and neural specification. AB - The prospect of using embryonic stem cell (ESC)-derived neural progenitors and neurons to treat neurological disorders has led to great interest in defining the conditions that guide the differentiation of ESCs, and more recently induced pluripotent stem cells (iPSCs), into neural stem cells (NSCs) and a variety of neuronal and glial subtypes. Over the past decade, researchers have looked to the embryo to guide these studies, applying what we know about the signaling events that direct neural specification during development. This has led to the design of a number of protocols that successfully promote ESC neurogenesis, terminating with the production of neurons and glia with diverse regional addresses and functional properties. These protocols demonstrate that ESCs undergo neural specification in two, three, and four dimensions, mimicking the cell-cell interactions, patterning, and timing that characterizes the in vivo process. We therefore propose that these in vitro systems can be used to examine the molecular regulation of neural specification. PMID- 20589756 TI - The role of apoptosis in mineralizing murine versus avian micromass culture systems. AB - Chondrocyte apoptosis is thought to be an important step in the calcification of cartilage in vivo; however, there are conflicting reports as to whether or not this apoptosis is a necessary precursor to mineralization. The goal of this study was to determine whether or not apoptosis is necessary for mineralization in an in vitro murine micromass model of endochondral ossification. C3H10T1/2 murine mesenchymal stem cells were plated in micromass culture in the presence of 4 mM inorganic phosphate with the addition of the apoptogens, camptothecin, or staurosporine, to induce apoptosis. The rate and total accumulation of mineralization was measured with (45)Ca uptake. In these studies, both apoptogens increased the rate of mineralization, with staurosporine increasing (45)Ca accumulation by about 2.5 times that of controls and camptothecin increasing total amounts of mineralization about 1.5 times that of controls. Inhibiting cell apoptosis with the caspase inhibitor, ZVAD-fmk, to prevent apoptosis, caused slower rates of (45)Ca uptake; however, total amounts of (45)Ca accumulation reached the same values by day 30 of culture. FTIR data showed mineralization in all samples treated with 4 mM inorganic phosphate, with the highest mineral to matrix ratios in the camptothecin treated samples. PMID- 20589757 TI - SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose stimulated insulin secretion in INS-1 cells. AB - Impairment of glucose-stimulated insulin secretion (GSIS) caused by glucolipotoxicity is an essential feature in type 2 diabetes mellitus (T2DM). Palmitate and eicosapentaenoate (EPA), because of their lipotoxicity and protection effect, were found to impair or restore the GSIS in beta cells. Furthermore, palmitate was found to up-regulate the expression level of sterol regulatory element-binding protein (SREBP)-1c and down-regulate the levels of pancreatic and duodenal homeobox (Pdx)-1 and glucagon-like peptide (GLP)-1 receptor (GLP-1R) in INS-1 cells. To investigate the underlying mechanism, the lentiviral system was used to knock-down or over-express SREBP-1c and Pdx-1, respectively. It was found that palmitate failed to suppress the expression of Pdx-1 and GLP-1R in SREBP-1c-deficient INS-1 cells. Moreover, down-regulation of Pdx-1 could cause the low expression of GLP-1R with/without palmitate treatment. Additionally, either SREBP-1c down-regulation or Pdx-1 over-expression could partially alleviate palmitate-induced GSIS impairment. These results suggested that sequent SREBP-1c-Pdx-1-GLP-1R signal pathway was involved in the palmitate caused GSIS impairment in beta cells. PMID- 20589758 TI - Sumoylation modulates a domain in CTCF that activates transcription and decondenses chromatin. AB - CTCF is a multipurpose transcription factor with activation, repression, and insulator activity. It also participates in regulating chromatin architecture by maintaining open chromatin and mediating long-range chromosomal interactions. Participation by CTCF in such diverse processes suggests that it has multiple functional domains that regulate transcription and modify chromatin structure. Using transient and integrated reporters, we identified a 107-amino-acid domain in CTCF's N-terminal region that is capable of transcriptional activation and chromatin decondensation. This domain demonstrated moderate transactivation when targeted to a promoter proximal position but showed little activity from more distal positions and on a natural promoter. By contrast, the activation domain dramatically decondensed the compact chromatin structure of a large transgene array, in a manner similar to the potent activation domain in VP16. In addition, the activation domain is subject to conjugation by SUMO, which reduced its transcriptional and chromatin opening activity. Moreover, mimicking full sumoylation by fusing Sumo-1 or -3 to the activation domain eliminated its transcriptional activity, but only Sumo-3 fusion prevented chromatin opening. We suggest that the activation domain's limited transactivation, but strong chromatin decondensation allows CTCF to establish and maintain open chromatin without necessarily activating transcription. Sumoylation may contribute to CTCF's enhancer blocking or repression functions by reducing transactivation and chromatin opening. PMID- 20589759 TI - E6AP ubiquitin ligase mediates ubiquitin-dependent degradation of peroxiredoxin 1. AB - E6-associated protein (E6AP) is a cellular ubiquitin protein ligase that mediates ubiquitylation and degradation of tumor suppressor p53 in conjunction with the high-risk human papillomavirus E6 protein. We previously reported that E6AP targets annexin A1 protein for ubiquitin-dependent proteasomal degradation. To gain a better understanding of the physiological function of E6AP, we have been seeking to identify novel substrates of E6AP. Here, we identified peroxiredoxin 1 (Prx1) as a novel E6AP-binding protein using a tandem affinity purification procedure coupled with mass spectrometry. Prx1 is a 25-kDa member of the Prx family, a ubiquitous family of antioxidant peroxidases that regulate many cellular processes through intracellular oxidative signal transduction pathways. Immunoprecipitation analysis showed that E6AP binds Prx1 in vivo. Pull-down experiments showed that E6AP binds Prx1 in vitro. Ectopic expression of E6AP enhanced the degradation of Prx1 in vivo. In vivo and in vitro ubiquitylation assays revealed that E6AP promoted polyubiquitylation of Prx1. RNAi-mediated downregulation of endogenous E6AP increased the level of endogenous Prx1 protein. Taken together, our data suggest that E6AP mediates the ubiquitin-dependent proteasomal degradation of Prx1. Our findings raise a possibility that E6AP may play a role in regulating Prx1-dependent intracellular oxidative signal transduction pathways. PMID- 20589760 TI - Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer: a phase 1-2 study. AB - BACKGROUND: The current study was conducted to evaluate the maximum tolerable dose of weekly gemcitabine administered simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC). METHODS: Patients with stage IIIA/B NSCLC received concurrently 63 grays radiation and 20 mg/m2 cisplatin Day 1 to 3 in Weeks 1 and 5, plus weekly gemcitabine at escalating doses (150-700 mg/m2) on Fridays after radiation to avoid radiosensitization. The authors assessed dose-limiting toxicities according to Common Toxicity Criteria. The primary endpoint was maximum tolerated dose (MTD) of gemcitabine. Tumor resectability, survival, and disease-free survival (DFS) were also determined. RESULTS: Forty-two patients were accrued, of whom 95% received radiation and 66% cisplatin as above. Weekly doses of gemcitabine were escalated to 700 mg/m2. Grade 3 dysphagia and 1 case of fatal, probably treatment related pulmonary deterioration established the MTD of gemcitabine at 550 mg/m2 weekly. Twenty-five patients underwent surgery, and histopathological complete regression was documented in 26% of these patients. Overall, median actuarial survival and DFS were 23.8 and 12.4 months, respectively. CONCLUSIONS: Gemcitabine at doses up to 550 mg/m2 weekly can be given simultaneously with radiation and cisplatin to patients with locally advanced NSCLC. Radical resection thereafter is feasible. The impact of this aggressive therapy should be evaluated further. PMID- 20589761 TI - Improved survival is associated with treatment at high-volume teaching facilities for patients with advanced stage laryngeal cancer. AB - BACKGROUND: Because of the multidisciplinary nature of treatment for advanced laryngeal cancer, the authors hypothesized that treatment at high-volume teaching/research facilities is associated with improved survival. METHODS: After exclusions, 19,326 patients who were diagnosed with advanced laryngeal cancer (stage III and IV) between 1996 and 2002 and who received treatment (chemoradiotherapy [CRT], total laryngectomy [TL], or radiotherapy [RT]) were analyzed from the National Cancer Database (NCDB). Facilities were classified into 6 groups (low-volume and high-volume teaching/research facilities, low volume and high-volume community cancer centers, and low-volume and high-volume community facilities). Multivariate proportional hazards regression modeling was used to determine 90-day, 365-day, and 4-year hazard ratio (HR) estimates. RESULTS: Treatment included TL (37.6%), CRT (29.4%), and RT alone (33%). Overall, 36.2% of patients were treated at high-volume teaching/research centers (average, 17.1 cases per year). Among all patients, 20% died within the first year. In multivariate models that were controlled for covariates, 90-day, 365-day, and 4 year HR estimates for death were lowest for high-volume teaching/research centers. CONCLUSIONS: Receiving treatment at high-volume teaching/research facilities was associated with improved survival. Undergoing total laryngectomy also was associated with improved survival. The current results suggested that the regionalization of care for patients with advanced-stage laryngeal cancer has occurred, because most patients were treated either at high-volume teaching/research facilities or at high-volume community cancer centers. Future studies should investigate the factors associated with better survival at high volume teaching/research facilities, such as quality of care, processes of care, and referral patterns. PMID- 20589762 TI - Quality of life, course and predictors of outcomes in community women with EDNOS and common eating disorders. AB - We investigated the 2-year course and putative predictors of outcome of 87 young community women with common eating disorders (n = 59, 68% with Eating Disorder not Otherwise Specified) following a health literacy (informational) intervention. Participants were recruited in 3-phases: community survey, interview and then invitation to a longitudinal study. The health literacy intervention was provided randomly to half participants at baseline and half at 1 year. Eating disorder symptoms and mental health related quality of life (MHQoL), general psychological function, help-seeking, and defence style were assessed at baseline, and after 2 years by questionnaire. Multiple linear regression analyses were used to identify features predictive of eating disorder symptom levels and MHQoL. Eating disorder psychopathology remained high and MHQoL remained poor. In the multivariate models, a higher baseline level of immature defence style significantly predicted higher levels of eating disorder symptoms, poorer MHQoL and more disability as measured by 'days out of role'. In addition, higher educational attainment, baseline general psychological disturbance, lower BMI and having main work outside the home were associated with poorer MHQoL. Women with common eating disorders followed to 2 years continued to be highly symptomatic and have poor quality of life. Psychological features important to outcome included an immature coping style and higher general psychological distress. PMID- 20589763 TI - Early response to ErbB2 over-expression in polarized Caco-2 cells involves partial segregation from ErbB3 by relocalization to the apical surface and initiation of survival signaling. AB - In several human cancers, ErbB2 over-expression facilitates the formation of constitutively active homodimers resistant to internalization which results in progressive signal amplification from the receptor, conducive to cell survival, proliferation, or metastasis. Here we report on studies of the influence of ErbB2 over-expression on localization and signaling in polarized Caco-2 and MDCK cells, two established models to study molecular trafficking. In these cells, ErbB2 is not over-expressed and shares basolateral localization with ErbB3. Over expression of ErbB2 by transient transfection resulted in partial separation of the receptors by relocalization of ErbB2, but not ErbB3, to the apical surface, as shown by biotinylation of the apical or basolateral surfaces. These results were confirmed by immunofluorescence and confocal microscopy. Polarity controls indicated that the relocalization of ErbB2 is not the result of depolarization of the cells. Biotinylation and confocal microscopy also showed that apical, but not basolateral ErbB2 is activated at tyrosine 1139. This phosphotyrosine binds adaptor protein Grb2, as confirmed by immunoprecipitation. However, we found that it does not initiate the canonical Grb2-Ras-Raf-Erk pathway. Instead, our data supports the activation of a survival pathway via Bcl-2. The effects of ErbB2 over-expression were abrogated by the humanized anti-ErbB2 monoclonal antibody Herceptin added only from the apical side. The ability of apical ErbB2 to initiate an altered downstream cascade suggests that subcellular localization of the receptor plays an important role in regulating ErbB2 signaling in polarized epithelia. PMID- 20589764 TI - Proliferation and differentiation of human adipocyte precursor cells: differences between the preperitoneal and subcutaneous compartments. AB - Human adipocyte precursor cells (APC) have been characterized in their proliferation and differentiation potential from subcutaneous, omental, and mesenteric depots, mostly from morbidly obese patients. Cells from the preperitoneal adipose compartment have not been characterized yet, least of all when obtained from normal weight subjects. The aim was to compare proliferation and differentiation of subcutaneous (SC) and preperitoneal (PP) APC derived from adipose tissue in healthy subjects with different body mass. SC and PP adipose tissue was obtained during surgery of inguinal hernias in five healthy non-obese subjects and three obese otherwise healthy men. APC, obtained by collagenase digestion, were cultured. Proliferation was assayed by cell counting and differentiation by oil red O staining and flow cytometry using Nile Red staining. Proliferation of SC was higher than PP APC. Such differences between both compartments were even higher in APC obtained from obese patients. Conversely PP APC differentiated earlier in vitro compared with SC cells. These results agree with published data on fat cell proliferation. However regarding differentiation, our data show that APC from deeper depots (in this case PP) differentiate earlier than subcutaneous APC. This is different to previous studies performed in mesenteric or omental adipose tissue. PMID- 20589765 TI - All better? How former anorexia nervosa patients define recovery and engaged in treatment. AB - The purpose of this study was to explore how individuals with anorexia nervosa (AN) engage in treatment and define recovery. A mixed methods design was used to triangulate the experience of 20 women with a history of AN. Interview data were analysed thematically to explore frequency of emergent themes and current eating disorder psychopathology was assessed using standardized self-report measures. Participants' mean age was 29.35 (SD = 12.11). Participants' scores were indicative of persistent psychopathology. Those with more involvement in treatment choice had better motivation to change and normalized eating. Participants' definition of recovery mapped on well to current research conceptualizations, though a substantial proportion of the group expressed some ambivalence around the concept. Results are interpreted in the context of self determination theory of motivation and suggest that patients should be involved collaboratively in the formulation of shared goals and concepts of recovery in treatment settings. PMID- 20589766 TI - Bariatric surgery: a primer for eating disorder professionals. AB - Obesity is a public health epidemic with medical, psychological and economic consequences. It continues to increase globally in prevalence and severity. Despite numerous behaviourally, medically or pharmacologically guided treatments, an effective non-surgical long-term treatment approach has not been identified. Bariatric surgery has surfaced as a viable option for a subset of individuals with medically complicated obesity who have failed non-surgical approaches. Pre operative evaluation followed by post-operative, longitudinal follow-up by a multidisciplinary team specializing in surgery, medicine, psychiatry/psychology, exercise science and nutrition constitutes recognized and necessary standard of care for these complex patients. More information is needed regarding factors that interfere with successful outcomes and mechanisms of optimal follow-up for bariatric surgery patients to prevent and detect post-operative medical, psychological and social difficulties. We will review these issues with a focus on issues relevant to eating disorders professionals. PMID- 20589767 TI - Quality assurance of specialised treatment of eating disorders using large-scale Internet-based collection systems: methods, results and lessons learned from designing the Stepwise database. AB - Computer-based quality assurance of specialist eating disorder (ED) care is a possible way of meeting demands for evaluating the real-life effectiveness of treatment, in a large-scale, cost-effective and highly structured way. The Internet-based Stepwise system combines clinical utility for patients and practitioners, and provides research-quality naturalistic data. Stepwise was designed to capture relevant variables concerning EDs and general psychiatric status, and the database can be used for both clinical and research purposes. The system comprises semi-structured diagnostic interviews, clinical ratings and self ratings, automated follow-up schedules, as well as administrative functions to facilitate registration compliance. As of June 2009, the system is in use at 20 treatment units and comprises 2776 patients. Diagnostic distribution (including subcategories of eating disorder not otherwise specified) and clinical characteristics are presented, as well as data on registration compliance. Obstacles and keys to successful implementation of the Stepwise system are discussed, including possible gains and on-going challenges inherent in large scale, Internet-based quality assurance. PMID- 20589768 TI - Psychological distress and risk for eating disorders in subgroups of dieters. AB - OBJECTIVE: The aim of the present study was to predict the risk of developing an eating disorder in subgroups of dieters, based on the adolescents own accounts of the reason for starting to diet. METHOD: Eighty-one dieters from a cohort of 595 adolescents (318 boys and 288 girls) aged 15 participated in the present prospective study. Personal interviews at both base-line and follow-up were combined with questionnaire data on depression, social phobia and self-esteem. RESULTS: Four mutually exclusive groups of dieters were identified: vanity dieters, overweight dieters, depressed dieters and feeling fat dieters. Depressed and feeling-fat dieters had a 15-fold risk of having a lifetime eating disorder at age 18 compared to vanity and overweight dieters. CONCLUSION: Typical teenage vanity dieting and dieting among overweight adolescents appears to be a benign practice, but adolescents dieting because of psychological distress have high risk of developing an eating disorder. PMID- 20589769 TI - Raman microscopy and surface-enhanced Raman scattering (SERS) for in situ analysis of biofilms. AB - Biofilms are communities of micro-organisms enclosed in a matrix of extracellular polymeric substances (EPS). They represent a ubiquitous form of microbial life on Earth. Detailed information on chemical composition and structure of the EPS matrix is relevant in medicine, industry and technological processes. Raman microscopy (RM) provides whole-organism fingerprints for biological samples with spatial resolution in the microm range and enables correlations between optical and chemical images to be made. Low water background makes RM beneficial for in situ studies of biofilms, since water is the major component of the biofilm matrix. In this paper we discuss the feasibility of RM for chemical characterization of different structures in a multispecies biofilm matrix, including microbial constituents and EPS. We show that by improving the sensitivity of RM with surface-enhanced Raman scattering (SERS) one can perform rapid biofilm analysis. In particular, by choosing appropriate SERS substrates and solving the problem of SERS measurement reproducibility one can carry out in situ study of different components in the complex biofilm matrix. PMID- 20589770 TI - Local-illuminated ultrathin silicon nanomembranes with photovoltaic effect and negative transconductance. PMID- 20589771 TI - Flexible, polymer-supported, Si wire array photoelectrodes. PMID- 20589772 TI - Ultra-broad optical amplification and two-colour amplified spontaneous emission in binary blends of insulated molecular wires. PMID- 20589773 TI - A color-tuneable organic light-emitting transistor. PMID- 20589774 TI - 6.5% Efficiency of polymer solar cells based on poly(3-hexylthiophene) and indene C(60) bisadduct by device optimization. AB - A power conversion efficiency of 6.48% was achieved for polymer solar cells based on poly(3-hexylthiophene) (P3HT) as donor and indene-C60 bisadduct (ICBA) as acceptor with an open-circuit voltage of 0.84 V, a short-circuit current of 10.61 mA/cm2, and a fill factor of 72.7% under irradiation at AM1.5G, 100 mW/cm2 at the optimized conditions of P3HT:ICBA = 1:1 (w/w), solvent annealing and pre-thermal annealing at 150 degrees C for 10 minutes. PMID- 20589775 TI - Conjugated oligoelectrolyte harnessed polyhedral oligomeric silsesquioxane as light-up hybrid nanodot for two-photon fluorescence imaging of cellular nucleus. AB - A water-soluble organic/inorganic hybrid nanodot based on polyhedral oligomeric silsesquioxane (POSS) and conjugated oligoelectrolyte is designed and synthesized for two-photon fluorescence imaging of cellular nucleus, which takes advantage of its small size (~3.3 nm) that imparts nucleus permeability and substantial DNA enhanced two-photon excited fluorescence that allows illuminating the nucleus with a high contrast. PMID- 20589776 TI - Separation of flavonoid and alkaloid using collagen fiber adsorbent. AB - Flavonoids and alkaloids are two major classes of plant compounds with biological activities, and they usually coexist in many medicinal herbs. In this study, a novel collagen fiber adsorbent (CFA) was prepared, and its application for adsorption chromatography separation of flavonoids and alkaloids was systematically investigated. The typical flavonoids, rutin and baicalin, and the typical alkaloids, matrine and caffeine, were selected as probe molecules for the investigations. The batch adsorption behaviors of these compounds on CFA in different solvents indicated that hydrogen bond plays a predominant role for the adsorption of flavonoid and alkaloid in pure ethanol, while the hydrophobic interaction plays a predominant role for the adsorption in water. In column chromatography separation, flavonoids were completely separated from alkaloids by a stepwise elution process with pure ethanol followed by aqueous ethanol solution. The two flavonoids, rutin and baicalin, were also well separated although the two alkaloids, matrine and caffeine, were washed out together. The optimal loading volume of sample solution (10 mg/mL) for the separation was determined as 0.66 mL/g CFA. Under these conditions, flavonoid and alkaloid were effectively separated with a recovery higher than 90% in 8 times repeated applications. PMID- 20589777 TI - Preparative enrichment and separation of astragalosides from Radix Astragali extracts using macroporous resins. AB - The enrichment and separation of astragalosides I-IV (AGs I-IV) were studied on eight macroporous resins in the present study. SA-3 resin offered the best adsorption and desorption capacities for AGs I-IV than other resins. The models of adsorption kinetics were investigated in order to elucidate the mechanism of adsorption. The pseudo-second-order model was the better choice than the pseudo first-order model to describe the adsorption behavior of AGs I-IV onto SA-3 resin. The equilibrium experimental data were well fitted to Langmuir and Freundlich isotherms. SA-3 resin adsorption chromatography tests were carried out to optimize the separation process of AGs I-IV from Radix Astragali extracts. With the optimum parameters for adsorption and desorption, the contents of AGs I IV were 8.78-, 11.60-, 10.52- and 11.28-fold increased with the recovery yields being 65.88, 90.92, 84.25 and 94.17%, respectively. The preparative enrichment and separation of AGs I-IV from Radix Astragali extracts can be easily and effectively achieved by SA-3 resin adsorption chromatography. The developed methodology can also be referenced for the separation of other active constituents from herbal materials and manufacture of Radix Astragali products. PMID- 20589778 TI - Modeling of chromatographic lipophilicity of food synthetic dyes estimated on different columns. AB - The retention behavior of some food synthetic dyes has been studied by RP-HPLC on chemically bonded C18, C8, C16 and CN stationary phases. Using methanol-ammonium acetate (0.08 mol/L, pH=6.76) as mobile phase, a linear behavior of retention parameters throughout the methanol fraction variance was obtained in all cases (r>0.99). The patterns of chromatographic behavior of the compounds illustrate high similarities between the C18, C8 and C16 columns, respectively. Highly significant correlations were obtained between experimental lipophilicity indices log k(w) and phi(0) estimated on C18 and C8 stationary phases and some computed log P-values. An extensive investigation made for quantitative structure-property (lipophilicity) relationships of studied dyes, using descriptors from Dragon software, multiple linear regression and genetic algorithm, revealed that the molecular descriptors appearing in the best models combine 2-D and 3-D aspects of the molecular structure. The most significant descriptors can be classified as radial distribution function, GETAWAY (autocorrelation), 3D-MoRSE signal, Burden eigenvalues and edge adjacency descriptors. PMID- 20589779 TI - Comparison between a linear ion trap and a triple quadruple MS in the sensitive detection of large peptides at femtomole amounts on column. AB - In addition to the importance of sample preparation and extract separation, MS detection is a key factor in the sensitive quantification of large undigested peptides. In this article, a linear ion trap MS (LIT-MS) and a triple quadrupole MS (TQ-MS) have been compared in the detection of large peptides at subnanomolar concentrations. Natural brain natriuretic peptide, C-peptide, substance P and D Junk-inhibitor peptide, a full D-amino acid therapeutic peptide, were chosen. They were detected by ESI and simultaneous MS(1) and MS(2) acquisitions. With direct peptide infusion, MS(2) spectra revealed that fragmentation was peptide dependent, milder on the LIT-MS and required high collision energies on the TQ-MS to obtain high-intensity product ions. Peptide adsorption on surfaces was overcome and peptide dilutions ranging from 0.1 to 25 nM were injected onto an ultra high-pressure LC system with a 1 mm id analytical column and coupled with the MS instruments. No difference was observed between the two instruments when recording in LC-MS(1) acquisitions. However, in LC-MS(2) acquisitions, a better sensitivity in the detection of large peptides was observed with the LIT-MS. Indeed, with the three longer peptides, the typical fragmentation in the TQ-MS resulted in a dramatic loss of sensitivity (> or = 10x). PMID- 20589780 TI - Characterization of bacterial lipid profiles by using rapid sample preparation and fast comprehensive two-dimensional gas chromatography in combination with mass spectrometry. AB - The bacteria fatty acid profile has been extensively studied for taxonomic classification purposes, since bacteria, in general, contain particular and rare fatty acids, compared with animal and plant tissues. As for any real-world sample type, the development of rapid and reliable methods for (i) sample identification (in this case, bacterium type), and (ii) constituent identification (in this instance, the fatty acid profile) is desirable. In this research, a half-an-hour procedure, to analyze bacteria, was developed: a 2-min one-step sample preparation step was followed by a relatively fast comprehensive 2D GC-MS separation (25 min). Furthermore, dedicated MS libraries were constructed for the identification of bacteria and fatty acids. Finally, data processing, only qualitative at this stage, was carried out with the support of a novel comprehensive 2D GC software. PMID- 20589781 TI - Comparison of common mobile-phase volume markers with polar-group-containing reversed-phase stationary phases. AB - A systematic study of the behavior of several common mobile-phase volume markers using traditional and polar-group-containing reversed-phase stationary phases is presented. Examined mobile-phase volume markers include two neutral molecules, uracil and thiourea, concentrated (0.10 M) and dilute (0.0001 M) KNO(3), and D(2)O. Mobile-phase volumes are examined over the entire reversed-phase mobile phase range of 100% water to 100% methanol or acetonitrile. The behavior of these mobile-phase volume markers is compared with a maximum theoretical value (i.e. the void volume), as determined by pycnometry. The data suggest that: (i) uracil begins to fail as a mobile-phase volume marker in mobile phases below about 40% strong solvent for polar group containing phases; (ii) in nearly all cases, the mobile-phase volume measured dynamically is smaller than the pycnometric void volume; (iii) a significant dependence of measured mobile-phase volume on salt concentration is seen on the polar endcapped phase, which is not observed on the traditional and embedded polar group phase; and (iv) D(2)O does not work well as a mobile-phase volume marker with polar-group-containing phases, possibly due to interaction with the stationary phase polar group. PMID- 20589782 TI - Extraction of crocin from saffron (Crocus sativus) using molecularly imprinted polymer solid-phase extraction. AB - A new molecularly imprinted polymer for extraction of crocin from saffron stigmas was prepared using gentiobiose (a glycoside moiety in crocin structure) as a template. Crocin binding to gentiobiose imprinted polymer (Gent-MIP) was studied in comparison with a blank nonimprinted polymer in aqueous media. Affinity of the Gent-MIP for the crocin was more than the nonimprinted polymer at all concentrations. In Scatchard analysis, the number of binding sites in each gram of polymer (maximum binding sites) and dissociation constant of crocin to binding sites were 18.4 micromol/g polymer and 11.2 microM, respectively. The Gent-MIP was then used as the sorbent in an SPE method for isolation and purification of crocin from methanolic extract of saffron stigmas. The recovery of crocin, safranal and picrocrocin was determined in washing and elution steps. The Gent MIP had significantly higher affinity for crocin than other compounds and enabled selective extraction of crocin with a high recovery (84%) from a complex mixture. The results demonstrated the possibility of using a part of a big molecule in preparing a molecularly imprinted polymer with a good selectivity for the main structure. PMID- 20589783 TI - Automated sample treatment with the injection of large sample volumes for the determination of contaminants and metabolites in urine. AB - This work reports the development of a simple and automated method for the quantitative determination of several contaminants (triazine, phenylurea, and phenoxyacid herbicides; carbamate insecticides and industrial chemicals) and their metabolites in human urine with a simplified sample treatment. The method is based on the online coupling of an extraction column with RP LC separation-UV detection; this coupling enabled fast online cleanup of the urine samples, efficiently eliminating matrix components and providing appropriate selectivity for the determination of such compounds. The variables affecting the automated method were optimized: sorbent type, washing solvent and time, and the sample volume injected. The optimized sample treatment reported here allowed the direct injection of large volumes of urine (1500 microL) into the online system as a way to improve the sensitivity of the method; limits of detection in the 1-10 ng/mL range were achieved for an injected volume of 1500 microL of urine, precision being 10% or better at a concentration level of 20 ng/mL. The online configuration proposed has advantages such as automation (all the steps involved in the analysis - injection of the urine, sample cleanup, analyte enrichment, separation and detection - are carried out automatically) with high precision and sensitivity, reducing manual sample manipulation to freezing and sample filtration. PMID- 20589784 TI - Liquid chromatography-tandem mass spectrometry method for simultaneous determination of cyclosporine A and its three metabolites AM1, AM9 and AM4N in whole blood and isolated lymphocytes in renal transplant patients. AB - A LC-MS/MS method was developed and validated for the determination of cyclosporine A (CsA) and its three phase 1 metabolites AM1, AM9, and AM4N in whole blood and lymphocytes isolated on the Histopaque gradient. 200 microL of whole blood was precipitated with 10 mol/L zinc sulfate in acetonitrile/methanol (40:60, v/v) and lymphocytes isolated from 1.5 mL blood were extracted with acetonitrile/methanol (40:60, v/v). The analytes and internal standard cyclosporine D were separated on RP column BEH C18, 2.1 x 50 mm, 1.7 microm using gradient LC-MS/MS analysis in positive electrospray mode. Time of analysis was 5 min. Linearity in blood was 5-2000 microg/L for CsA, AM1, and AM9; 2-500 microg/L for AM4N; and 2-500 microg/L for all substances in lymphocytes. Coefficient of variations was 1.8-9.8% and recovery was 92.0-110.0%. The method was used in early and chronic renal transplant patients for therapeutic drug monitoring of CsA to compare either its share in lymphocytes as target organ or binding to one lymphocyte. The same parameters were calculated for all metabolites tested. PMID- 20589790 TI - [Gene therapy for hemophilia B]. PMID- 20589791 TI - [A new, sixth human malaria parasite]. PMID- 20589792 TI - [Alternative paths to multidrug-resistant bacteria via reactive oxygen species]. PMID- 20589793 TI - [Trypanosomes in focus]. PMID- 20589795 TI - [Formulation interlaboratory tests of the Central Laboratory of German pharmacists (ZL). Quality assurance in pharmacy]. PMID- 20589798 TI - [The new drug formulary (NDF) of the German drug codex]. PMID- 20589800 TI - [Cytotoxic drugs production in the pharmacy. Trends and perspectives]. PMID- 20589801 TI - [Extemporaneous formulas from the viewpoint of dermatology. Obsolete or up-to date?]. PMID- 20589803 TI - [Glucocorticoid containing extemporaneous formulations. Rational for use in dermatology]. PMID- 20589804 TI - [Quality skin care preparations in the pharmacy. Tailor-made medicine--patient friendly and safe]. PMID- 20589805 TI - [Compounding of ophthalmic drugs in the pharmacy. Special care must be taken!]. PMID- 20589812 TI - [Aegean wallflower--an ornamental and useful plant]. PMID- 20589818 TI - Label-free, real-time monitoring of biomass processing with stimulated Raman scattering microscopy. PMID- 20589819 TI - A golden episode continues Fenton's colorful story. PMID- 20589820 TI - Metal complexes as protein kinase inhibitors. PMID- 20589821 TI - Enantioselective oxidative cross-coupling reaction of 3-indolylmethyl C-H bonds with 1,3-dicarbonyls using a chiral Lewis acid-bonded nucleophile to control stereochemistry. PMID- 20589822 TI - A monomeric dilithio methandiide with a distorted trans-planar four-coordinate carbon. PMID- 20589823 TI - Cloning and characterization of the biosynthetic gene cluster of 16-membered macrolide antibiotic FD-891: involvement of a dual functional cytochrome P450 monooxygenase catalyzing epoxidation and hydroxylation. AB - FD-891 is a 16-membered cytotoxic antibiotic macrolide that is especially active against human leukemia such as HL-60 and Jurkat cells. We identified the FD-891 biosynthetic (gfs) gene cluster from the producer Streptomyces graminofaciens A 8890 by using typical modular type I polyketide synthase (PKS) genes as probes. The gfs gene cluster contained five typical modular type I PKS genes (gfsA, B, C, D, and E), a cytochrome P450 gene (gfsF), a methyltransferase gene (gfsG), and a regulator gene (gfsR). The gene organization of PKSs agreed well with the basic polyketide skeleton of FD-891 including the oxidation states and alpha-alkyl substituent determined by the substrate specificities of the acyltransferase (AT) domains. To clarify the involvement of the gfs genes in the FD-891 biosynthesis, the P450 gfsF gene was inactivated; this resulted in the loss of FD-891 production. Instead, the gfsF gene-disrupted mutant accumulated a novel FD-891 analogue 25-O-methyl-FD-892, which lacked the epoxide and the hydroxyl group of FD-891. Furthermore, the recombinant GfsF enzyme coexpressed with putidaredoxin and putidaredoxin reductase converted 25-O-methyl-FD-892 into FD-891. In the course of the GfsF reaction, 10-deoxy-FD-891 was isolated as an enzymatic reaction intermediate, which was also converted into FD-891 by GfsF. Therefore, it was clearly found that the cytochrome P450 GfsF catalyzes epoxidation and hydroxylation in a stepwise manner in the FD-891 biosynthesis. These results clearly confirmed that the identified gfs genes are responsible for the biosynthesis of FD-891 in S. graminofaciens. PMID- 20589824 TI - Protease-activatable collagen targeting based on protein cyclization. PMID- 20589825 TI - Electronic properties of propylamine-functionalized single-walled carbon nanotubes. AB - We present resonant Raman measurements on single-walled carbon nanotubes (SWCNT) functionalized with propylamine groups at different degrees. Direct nucleophilic addition based on in situ generated primary amides is used for attaching n propylamine to the sidewalls of SWCNTs. The influence of the amino functionalities on the electronic structure of the nanotubes is investigated. From the Raman resonance profiles of the radial breathing modes (RBMs), the chiral indices of the corresponding tubes are assigned. We observe significant redshifts of the transition energies and a broadening of the resonance windows due to chemical modification of SWCNTs. Similar redshifts are derived from the analysis of the NIR/Vis transmission spectrum. The relative Raman intensities of the functionalized samples and the evaluation of their transmission spectra indicate a diameter dependence of the reactivity as it has been observed for other moieties. By analyzing the defect induced D mode we observe a considerable degree of functionalization accompanied by an almost unharmed tube structure, which ensures that the observed effects are mainly driven by changes of the electronic structure. PMID- 20589826 TI - New far-red and near-infrared fluorescent probes with large Stokes shifts for dual covalent labeling of DNA. PMID- 20589827 TI - Tuning the stability and reactivity of metal-bound alkylperoxide by remote site substitution of the ligand. AB - An alkylperoxonickel(II) complex with hydrotris(3,5-diisopropyl-4-bromo-1 pyrazolyl)borate, [Ni(II)(OOtBu)(Tp(iPr2,Br))] (3 a), is synthesized, and its chemical properties are compared with those of the prototype non-brominated ligand derivative [Ni(II)(OOtBu)(Tp(iPr2))] (3 b; Tp(iPr2)=hydrotris(3,5 diisopropyl-1-pyrazolyl)borate). Same synthetic procedures for the prototype 3 b and its precursors can be employed to the synthesis of the Tp(iPr2,Br) analogues. The dimeric nickel(II)-hydroxo complex, [(Ni(II)Tp(iPr2,Br))(2)(mu-OH)(2)] (2 a), can be synthesized by the base hydrolysis of the labile complexes [Ni(II)(Y)(Tp(iPr2,Br))] (Y=NO(3) (1 a), OAc (1 a')), which are obtained by the metathesis of NaTp(iPr2,Br) with the corresponding nickel(II) salts, and the following dehydrative condensation of 2 a with the stoichiometric amount of tert butylhydroperoxide yields 3 a. The unique structural characteristics of the prototype 3 b, that is, highly distorted geometry of the nickel center and intermediate coordination mode of the O--O moiety between eta(1) and eta(2), are kept in the brominated ligand analogue 3 a. The introduction of the electron withdrawing substitutents on the distal site of Tp(R) affects the thermal stability and reactivity of the nickel(II)-alkylperoxo species. PMID- 20589828 TI - Single-crystalline ZnO nanowire bundles: synthesis, mechanism and their application in dielectric composites. AB - Single-crystalline ZnO nanowire bundles have been synthesized in large-scale by an improved microemulsion method in the presence of excessive hydrate hydrazine and dodecyl benzene sulfonic acid sodium salt (DBS) in xylene. The product is characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). The result shows that the bundle is composed by many oriented single-crystalline ZnO nanowires with a length of about 1 mum and a diameter of about 20-30 nm. The influence of DBS, hydrazine and the reaction time on the morphology of final product and the formation mechanism of such nanostructures were discussed; the application in the dielectric composites is also studied. PMID- 20589829 TI - Leptin potentiates antiproliferative action of cAMP elevation via protein kinase A down-regulation in breast cancer cells. AB - Previously, we have shown that leptin potentiates the antiproliferative action of cAMP elevating agents in breast cancer cells and that the protein kinase A (PKA) inhibitor KT-5720 prevented the antiproliferative effects induced by the leptin plus cAMP elevation. The present experiments were designed to gain a better understanding about the PKA role in the antitumor interaction between leptin and cAMP elevating agents and on the underlying signaling pathways. Here we show that exposure of MDA-MB-231 breast cancer cells to leptin resulted in a strong phosphorylation of both ERK1/2 and STAT3. Interestingly, intracellular cAMP elevation upon forskolin pretreatment completely abrogated both ERK1/2 and STAT3 phosphorylation in response to leptin and was accompanied by a consistent CREB phosphorylation. Notably, leptin plus forskolin cotreatments resulted in a strong decrease of both PKA regulatory RIalpha and catalytic subunits protein levels. Importantly, pretreatment with the PKA inhibitor KT-5720 blocked the forskolin induced CREB phosphorylation and prevented both the inhibition by forskolin of leptin-induced ERK1/2 and STAT3 phosphorylation and the PKA subunits down regulation induced by the combination of leptin and forskolin. Altogether, our results indicate that leptin-dependent signaling pathways are influenced by cAMP elevation and identify PKA as relevantly involved in the pharmacological antitumor interaction between leptin and cAMP elevating drugs in MDA-MB-231 cells. We propose a molecular model by which PKA confers its effects. Potential therapeutic applications by our data will be discussed. PMID- 20589831 TI - Effect of leukotriene D4 on mouse embryonic stem cell migration and proliferation: involvement of PI3K/Akt as well as GSK-3beta/beta-catenin signaling pathways. AB - The actual leukotriene D(4) (LTD(4)) signaling pathways that regulate cell proliferation have not been elucidated thoroughly although fatty acid and its metabolites play a key role in regulations of embryonic functions. Thus, this study investigated the response of mouse embryonic stem (ES) cells exposed to LTD(4) and elucidated the signaling pathways as well. LTD(4) increased DNA synthesis in concentration-dependent (>=10(-7) M) and time-dependent (>=12 h) manners, as determined by [(3)H] thymidine incorporation and increased cell number. LTD(4) induced the phosphorylation of signal transducer and activator of transcription-3 (STAT3) and the increase of intracellular Ca(2+) levels via cysteinyl leukotriene (CysLT) 1 and 2 receptors. LTD(4) increased Akt activation and calcineurin expression, which were blocked by STAT3 inhibitor and calcium chelators. LTD(4)-induced glycogen synthase kinase (GSK)-3beta phosphorylation was decreased by LY294002, Akt inhibitor, and cyclosporine A. LTD(4) inhibited the phosphorylation of beta-catenin. In addition, LTD(4)-stimulated migration through increased activation of focal adhesion kinase (FAK) and paxillin which were blocked by Akt inhibitor and cyclosporine A. LTD(4)-induced increases in protooncogene and cell cycle regulatory proteins were blocked by cyclosporine A, FAK siRNA, and beta-catenin siRNA. In conclusion, LTD(4)-stimulated mouse ES cell proliferation and migration via STAT3, phosphoinositide 3-kinases (PI3K)/Akt, Ca(2+)-calcineurin, and GSK-3beta/beta-catenin pathway. PMID- 20589830 TI - Regulation of lipopolysaccharide-induced inflammatory response and endotoxemia by beta-arrestins. AB - Beta-arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that beta arrestin-1 (beta-arr-1) and -2 knockout (KO) mice are protected from TLR4 mediated endotoxic shock and lethality. To identify the potential mechanisms involved, we examined the plasma levels of inflammatory cytokines/chemokines in the wild-type (WT) and beta-arr-1 and -2 KO mice after lipopolysaccharide (LPS, a TLR4 ligand) injection. Consistent with lethality, LPS-induced inflammatory cytokine levels in the plasma were markedly decreased in both beta-arr-1 and -2 KO, compared to WT mice. To further explore the cellular mechanisms, we obtained splenocytes (separated into CD11(b+) and CD11(b-) populations) from WT, beta-arr 1, and -2 KO mice and examined the effect of LPS on cytokine production. Similar to the in vivo observations, LPS-induced inflammatory cytokines were significantly blocked in both splenocyte populations from the beta-arr-2 KO compared to the WT mice. This effect in the beta-arr-1 KO mice, however, was restricted to the CD11(b-) splenocytes. Our studies further indicate that regulation of cytokine production by beta-arrestins is likely independent of MAPK and IkappaBalpha-NFkappaB pathways. Our results, however, suggest that LPS induced chromatin modification is dependent on beta-arrestin levels and may be the underlying mechanistic basis for regulation of cytokine levels by beta arrestins in vivo. Taken together, these results indicate that beta-arr-1 and -2 mediate LPS-induced cytokine secretion in a cell-type specific manner and that both beta-arrestins have overlapping but non-redundant roles in regulating inflammatory cytokine production and endotoxic shock in mice. PMID- 20589833 TI - Syntaxin 16: unraveling cellular physiology through a ubiquitous SNARE molecule. AB - Syntaxin 16 (Syx16) is member of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) family of molecules that functions in membrane fusion in eukaryotic cells. A rather ubiquitously expressed, tail anchored membrane protein localized mainly at the trans-Golgi network (TGN), it mediates primarily retrograde endosomal-TGN transport. In spite of its ubiquitous expression, Syx16 has specific and interesting roles in the physiology of specialized cells, including Glut4 dynamics, dendritic outgrowth-related membrane traffic, and cytokinesis. We discussed these physiological functions of Syx16 in the light of what is known of its subcellular localization, vesicular trafficking pathways involved, cognate SNARE partners and other interacting proteins. Further, we speculate on some possible pathophysiological roles of Syx16. PMID- 20589834 TI - Elevated expression of TMEM205, a hypothetical membrane protein, is associated with cisplatin resistance. AB - Development of cisplatin resistance in cancer cells appears to be a consequence of multiple epigenetic alterations in genes involved in DNA damage repair, proto oncogenes, apoptosis, transporters, transcription factors, etc. In this study, we found that expression of the hypothetical transmembrane protein TMEM205 (previously known as MBC3205) is associated with cisplatin resistance. TMEM205 was first detected by functional cloning from a retroviral cDNA library made from human cisplatin-resistant (CP-r) cells. TMEM205 is predicted to be a transmembrane protein, but its expression, localization, and function have not previously been investigated. A polyclonal antibody directed to the TMEM205 protein was raised in our laboratory. Using this antibody, it was demonstrated that this protein is located at the cell surface. Its expression is increased in our cisplatin-selected CP-r cell lines, as demonstrated by immunoblotting, confocal examination, and immuno-electron microscopy. Stable transfection of the TMEM205 gene confers resistance to cisplatin by approximately 2.5-fold. Uptake assays with Alexa Fluor-cisplatin showed reduced accumulation in CP-r KB-CP.3 and KB-CP.5 cells, and in TMEM205-transfected cells. Analysis of TMEM205 expression profiles in normal human tissues indicates a differential expression pattern with higher expression levels in the liver, pancreas, and adrenal glands. These results indicate that a novel mechanism for cisplatin resistance is mediated by TMEM205, and also suggest that overexpression of TMEM205 in CP-r cells may be valuable as a biomarker or target in cancer chemotherapy. PMID- 20589832 TI - Restoration of DNA-binding and growth-suppressive activity of mutant forms of p53 via a PCAF-mediated acetylation pathway. AB - Tumor-derived mutant forms of p53 compromise its DNA binding, transcriptional, and growth regulatory activity in a manner that is dependent upon the cell-type and the type of mutation. Given the high frequency of p53 mutations in human tumors, reactivation of the p53 pathway has been widely proposed as beneficial for cancer therapy. In support of this possibility p53 mutants possess a certain degree of conformational flexibility that allows for re-induction of function by a number of structurally different artificial compounds or by short peptides. This raises the question of whether physiological pathways for p53 mutant reactivation also exist and can be exploited therapeutically. The activity of wild-type p53 is modulated by various acetyl-transferases and deacetylases, but whether acetylation influences signaling by p53 mutant is still unknown. Here, we show that the PCAF acetyl-transferase is down-regulated in tumors harboring p53 mutants, where its re-expression leads to p53 acetylation and to cell death. Furthermore, acetylation restores the DNA-binding ability of p53 mutants in vitro and expression of PCAF, or treatment with deacetylase inhibitors, promotes their binding to p53-regulated promoters and transcriptional activity in vivo. These data suggest that PCAF-mediated acetylation rescues activity of at least a set of p53 mutations. Therefore, we propose that dis-regulation of PCAF activity is a pre-requisite for p53 mutant loss of function and for the oncogenic potential acquired by neoplastic cells expressing these proteins. Our findings offer a new rationale for therapeutic targeting of PCAF activity in tumors harboring oncogenic versions of p53. PMID- 20589836 TI - Role of calcium and ROS in cell death induced by polyunsaturated fatty acids in murine thymocytes. AB - We investigated the mechanisms whereby omega-3 and -6 polyunsaturated fatty acids (PUFAs) cause cell death of mouse thymocytes using flow cytometry, focusing on the respective roles of intracellular calcium concentration, [Ca(2+)](i) and reactive oxygen species (ROS). We applied the C-22, 20, and 18 carbon omega-3 (DHA, EPA, ALA) and omega-6 (DTA, ARA, and LNA) fatty acids to isolated thymocytes and monitored cell death using the DNA-binding dye, propidium iodide. When applied at 20 uM concentration, omega-3 fatty acids killed thymocytes over a period of 1 h with a potency of DHA > EPA > ALA. The omega-6 PUFAs were more potent. The C18 omega-6 fatty acid, LNA, was the most potent, followed by DHA and ARA. Cell death was always accompanied by an increase in the levels of [Ca(2+)](i) and ROS. Both increases were in proportion to the potency of the PUFAs in inducing cell death. Removing extracellular calcium did not prevent the elevation in [Ca(2+)](i) nor cell death. However, the intracellular calcium chelator, BAPTA, almost totally reduced both the elevation in [Ca(2+)](i) and cell death, while vitamin E reduced the elevation in ROS and cell death. BAPTA also prevented the elevation in ROS, but vitamin E did not prevent the elevation in [Ca(2+)](i). Thapsigargin, which depletes endoplasmic reticulum calcium, blocked the elevation in [Ca(2+)](i), but CCCP, a mitochondrial calcium uptake inhibitor, did not. These results suggest that the six PUFAs we studied kill thymocytes by causing release of calcium from endoplasmic reticulum, which causes release of ROS from mitochondria which leads to cell death. PMID- 20589835 TI - Regulation of MT1-MMP activity by beta-catenin in MDCK non-cancer and HT1080 cancer cells. AB - Past studies on beta-catenin in cancer cells focused on nuclear localized beta catenin and its involvement in the Wnt pathway. Our goal here was to investigate the function of beta-catenin in both the cytoplasm and nucleus on the regulation of MT1-MMP expression and activity. We found that beta-catenin in MDCK non-cancer cells inhibited the cell surface localization of MT1-MMP, and thus its proteolytic activity on pro-MMP2 activation, via direct interaction with the 18 amino-acid cytoplasmic tail of MT1-MMP in the cytoplasm. In contrast, beta catenin in HT1080 cancer cells enhanced the activity of MT1-MMP by entering the nucleus and activating transcription factor Tcf-4/Lef, and elevating the level of MT1-MMP protein. We also found that enhancement of cell growth in three dimensional (3-D)/two-dimensional (2-D) type I collagen gels and of cell migration by MT1-MMP were inhibited by beta-catenin in MDCK cells, whereas these functions were enhanced in HT1080 cells. In addition, regulation of MT1-MMP by beta-catenin involved E-cadherin in MDCK cells and Wnt-3a in HT1080 cells. Taken together, our results present a differential effect of cytoplasmic and nuclear beta-catenin on MT1-MMP activity in non-cancer cells versus cancer cells. These differences were most probably due to different subcellular locations and different involved pathways of beta-catenin in these cells. PMID- 20589837 TI - Adipocytes decrease Runx2 expression in osteoblastic cells: roles of PPARgamma and adiponectin. AB - The mechanisms through which bone marrow adipocytes might influence differentiation and function of osteoblasts are not completely understood. To investigate the direct effects of bone marrow fat cells on osteoblast function, an ex vivo co-culture system was utilized comprising either primary fat cells or differentiated 3T3-L1 adipocytes and osteoblastic cells on transwells. In co culture, both adipocytes and osteoblastic cells were differentiated into adipocytes or osteoblasts, respectively, before culturing on transwells. Co culture with either primary fat cells or fully differentiated 3T3-L1 adipocytes significantly decreased mRNA and protein expression of runt-related transcription factor 2 (Runx2) in osteoblastic cells. An increase in mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARgamma) occurred concomitantly with the reduction of Runx2 expression. Adiponectin concentration was increased in the media by co-culture. In addition, co-culture with conditioned media from fat cells increased PPARgamma promoter activity and decreased Runx2 promoter activity. Knockdown of PPARgamma or adiponectin receptor 1 in osteoblastic cells by siRNA prevented the down-regulation of mRNA expression of Runx2 in osteoblastic cells cultured with fully differentiated 3T3-L1 cells. Furthermore, co-transfection with PPARgamma decreased Runx2 promoter activity. A marker of osteogenesis, alkaline phosphatase activity in osteoblastic cells was significantly decreased by co-culture. Annexin V/propidium iodide staining showed that co-culture did not induce apoptosis in osteoblastic cells. Thus, we conclude that adipocytes modulate key metabolic functions of osteoblasts through the release of secretory products. PPARgamma plays a key role in mediating the effects of adipocytes on osteoblasts. PMID- 20589838 TI - Continuous scalable blood filtration device using inertial microfluidics. AB - Cell separation is broadly useful for applications in clinical diagnostics, biological research, and potentially regenerative medicine. Recent attention has been paid to label-free size-based techniques that may avoid the costs or clogging issues associated with centrifugation and mechanical filtration. We present for the first time a massively parallel microfluidic device that passively separates pathogenic bacteria cells from diluted blood with macroscale performance. The device was designed to process large sample volumes in a high throughput, continuous manner using 40 single microchannels placed in a radial array with one inlet and two rings of outlets. Each single channel consists of a short focusing, gradual expansion and collection region and uses unique differential transit times due to size-dependent inertial lift forces as a method of cell separation. The gradual channel expansion region is shown to manipulate cell equilibrium positions close to the microchannel walls, critical for higher efficiency collection. We demonstrate >80% removal of pathogenic bacteria from blood after two passes of the single channel system. The massively parallel device can process 240 mL/h with a throughput of 400 million cells/min. We expect that this parallelizable, robust, and label-free approach would be useful for filtration of blood as well as for other cell separation and concentration applications from large volume samples. PMID- 20589839 TI - Germination and inactivation of Bacillus subtilis spores induced by moderate hydrostatic pressure. AB - In this study, we investigated the mechanisms of spore inactivation by high pressure at moderate temperatures to optimize the sterilization efficiency of high-pressure treatments. Bacillus subtilis spores were first subjected to different pressure treatments ranging from 90 to 550 MPa at 40 degrees C, with holding times from 10 min to 4 h. These treatments alone caused slight inactivation, which was related to the pressure-induced germination of the spores. After these pressures treatments, the sensitivity of these processed spores to heat (80 degrees C/10 min) or to high pressure (350 MPa/40 degrees C/10 min) was tested to determine the pressure-induced germination rate and the advancement of the spores in the germination process. The subsequent heat or pressure treatments were applied immediately after decompression from the first pressure treatment or after a holding time at atmospheric pressure. As already known, the spore germination is more efficient at low pressure level than at high pressure level. Our results show that this low germination efficiency at high pressure seemed not to be related either to a lower induction or a difference in the induction mechanisms but rather to an inhibition of enzyme activities which are involved in germination process. In fact, high pressure was necessary and very efficient in inducing spore germination. However, it seemed to slow the enzymatic digestion of the cortex, which is required for germinated spores to be inactivated by pressure. Although these results indicate that high-pressure treatments are more efficient when the two treatments are combined, a small spore population still remained dormant and was not inactivated with any holding time or pressure level. PMID- 20589840 TI - Preparation of connexin43-integrated giant Liposomes by a baculovirus expression liposome fusion method. AB - Connexin-43 (Cx43) containing giant liposomes (GL) were prepared by a baculovirus expression-liposome fusion method. Recombinant budded viruses expressing Cx43 were prepared and then fused with GLs containing DOPG/DOPC at pH 4.5. Connexon formation on the GL membrane was observed by transmission electron microscope. Hydrophilic fluorescent dye transfers were observed through a Cx43-mediated pathway not only between Sf9 (Spodoptera frugiperda) cells with Cx43 but also from giant Cx43 liposomes to Cx43-expressing U2OS cells (human osteosarcoma cell). The functional connexin-containing liposome is expected to be useful for cellular cytosolic delivery systems. The original orientation and function of Cx43 was maintained after integration into the liposomes. The liposome fusion method will create new opportunities as a tool for analysis of channel membrane proteins. PMID- 20589841 TI - Valorization of an industrial organosolv-sugarcane bagasse lignin: Characterization and use as a matrix in biobased composites reinforced with sisal fibers. AB - In the present study, the main focus was the characterization and application of the by-product lignin isolated through an industrial organosolv acid hydrolysis process from sugarcane bagasse, aiming at the production of bioethanol. The sugarcane lignin was characterized and used to prepare phenolic-type resins. The analysis confirmed that the industrial sugarcane lignin is of HGS type, with a high proportion of the less substituted aromatic ring p-hydroxyphenyl units, which favors further reaction with formaldehyde. The lignin-formaldehyde resins were used to produce biobased composites reinforced with different proportions of randomly distributed sisal fibers. The presence of lignin moieties in both the fiber and matrix increases their mutual affinity, as confirmed by SEM images, which showed good adhesion at the biocomposite fiber/matrix interface. This in turn allowed good load transference from the matrix to the fiber, leading to biobased composites with good impact strength (near 500 J m(-1) for a 40 wt% sisal fiber-reinforced composite). The study demonstrates that sugarcane bagasse lignin obtained from a bioethanol plant can be used without excessive purification in the preparation of lignocellulosic fiber-reinforced biobased composites displaying high mechanical properties. PMID- 20589843 TI - Efficient phase separation and product recovery in organic-aqueous bioprocessing using supercritical carbon dioxide. AB - Biphasic hydrocarbon functionalizations catalyzed by recombinant microorganisms have been shown to be one of the most promising approaches for replacing common chemical synthesis routes on an industrial scale. However, the formation of stable emulsions complicates downstream processing, especially phase separation. This fact has turned out to be a major hurdle for industrial implementation. To overcome this limitation, we used supercritical carbon dioxide (scCO(2)) for both phase separation and product purification. The stable emulsion, originating from a stereospecific epoxidation of styrene to (S)-styrene oxide, a reaction catalyzed by recombinant Escherichia coli, could be destabilized efficiently and irreversibly, enabling complete phase separation within minutes. By further use of scCO(2) as extraction agent, the product (S)-styrene oxide could be obtained with a purity of 81% (w/w) in one single extraction step. By combining phase separation and product purification using scCO(2), the number of necessary workup steps can be reduced to one. This efficient and easy to use technique is generally applicable for the workup of biphasic biocatalytic hydrocarbon functionalizations and enables a cost effective downstream processing even on a large scale. PMID- 20589842 TI - Systematizing the generation of missing metabolic knowledge. AB - Genome-scale metabolic network reconstructions are built from all of the known metabolic reactions and genes in a target organism. However, since our knowledge of any organism is incomplete, these network reconstructions contain gaps. Reactions may be missing, resulting in dead-ends in pathways, while unknown gene products may catalyze known reactions. New computational methods that analyze data, such as growth phenotypes or gene essentiality, in the context of genome scale metabolic networks, have been developed to predict these missing reactions or genes likely to fill these knowledge gaps. A growing number of experimental studies are appearing that address these computational predictions, leading to discovery of new metabolic capabilities in the target organism. Gap-filling methods can thus be used to improve metabolic network models while simultaneously leading to discovery of new metabolic gene functions. PMID- 20589844 TI - Mechanism of antibody reduction in cell culture production processes. AB - We recently observed a significant disulfide reduction problem during the scale up of a manufacturing process for a therapeutic antibody using a CHO expression system. Under certain conditions, extensive reduction of inter-chain disulfide bonds of an antibody produced by CHO cell culture may occur during the harvest operations and/or the protein A chromatography step, resulting in the observation of antibody fragments (light chain, heavy chain, and various combination of both) in the protein A pools. Although all conditions leading to disulfide reduction have not been completely identified, an excessive amount of mechanical cell lysis generated at the harvest step appears to be an important requirement for antibody reduction (Trexler-Schmidt et al., 2010). We have been able to determine the mechanism by which the antibody is reduced despite the fact that not all requirements for antibody reduction were identified. Here we present data strongly suggesting that the antibody reduction was caused by a thioredoxin system or other reducing enzymes with thioredoxin-like activity. The intracellular reducing enzymes and their substrates/cofactors apparently were released into the harvest cell culture fluid (HCCF) when cells were exposed to mechanical cell shear during harvest operations. Surprisingly, the reducing activity in the HCCF can last for a long period of time, causing the reduction of inter-chain disulfide bonds in an antibody. Our findings provide a basis for designing methods to prevent the antibody reduction during the manufacturing process. PMID- 20589845 TI - Complete anaerobic mineralization of pentachlorophenol (PCP) under continuous flow conditions by sequential combination of PCP-dechlorinating and phenol degrading consortia. AB - Complete mineralization of 50 uM of pentachlorophenol (PCP) was achieved anaerobically under continuous flow conditions using two columns connected in series with a hydraulic retention time of 14.2 days, showing the highest reported mineralization rate yet of 3.5 uM day(-1). The first column, when injected with a reductive PCP dechlorinating consortium, dechlorinated PCP to mainly phenol and traces of 3-chlorophenol (3-CP) using lactate supplied continuously as an electron donor. The second column, with an anaerobic phenol degrading consortium, decomposed phenol and 3-CP under iron-reducing conditions with substantial fermentative degradation of organic compounds. When 20 mM of lactate was introduced into the first column, the phenol degradation activity of the second column was lost in a short period of time, because the amorphous Fe(III) oxide (FeOOH) that had been packed in the column before use was depleted by lactate metabolites, such as acetate and propionate, flowing into the second column from the first column. The complete mineralization of PCP was maintained for a long period by reducing the lactate concentration to 4 mM, effectively extending the longevity of second-column activity with no depletion of FeOOH for more than 200 pore volumes (corresponding to 3,000 days). The carbon balance showed that 50 uM PCP and 4 mM lactate in the influent had transformed to CO(2) (81%) and CH(4) (3%) and had contributed to biomass growth (8%). A comparison of the microbial consortia introduced into the columns and those flowing out from the columns suggested that the introduced population did not flow out during the experiments, although the microbial composition of the phenol column was considered to be affected by the inflow of microbes from the PCP dechlorination column. These results suggest that a sequential combination of reductive dechlorinating and anaerobic oxidizing consortia is useful for anaerobic remediation of chlorinated aromatic compounds in a microbial permeable reactive barrier. PMID- 20589846 TI - Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells. AB - Mouse embryonic stem cell (ESC) lines, and more recently human ESC lines, have become valuable tools for studying early mammalian development. Increasing interest in ESCs and their differentiated progeny in drug discovery and as potential therapeutic agents has highlighted the fact that current two dimensional (2D) static culturing techniques are inadequate for large-scale production. The culture of mammalian cells in three-dimensional (3D) agitated systems has been shown to overcome many of the restrictions of 2D and is therefore likely to be effective for ESC proliferation. Using murine ESCs as our initial model, we investigated the effectiveness of different 3D culture environments for the expansion of pluripotent ESCs. Solohill Collagen, Solohill FACT, and Cultispher-S microcarriers were employed and used in conjunction with stirred bioreactors. Initial seeding parameters, including cell number and agitation conditions, were found to be critical in promoting attachment to microcarriers and minimizing the size of aggregates formed. While all microcarriers supported the growth of undifferentiated mESCs, Cultispher-S out performed the Solohill microcarriers. When cultured for successive passages on Cultispher-S microcarriers, mESCs maintained their pluripotency, demonstrated by self-renewal, expression of pluripotency markers and the ability to undergo multi lineage differentiation. When these optimized conditions were applied to unweaned human ESCs, Cultispher-S microcarriers supported the growth of hESCs that retained expression of pluripotency markers including SSEA4, Tra-1-60, NANOG, and OCT-4. Our study highlights the importance of optimization of initial seeding parameters and provides proof-of-concept data demonstrating the utility of microcarriers and bioreactors for the expansion of hESCs. PMID- 20589848 TI - Unusual photoinduced electron transfer from a zinc porphyrin to a tetrapyridyl free-base porphyrin in a noncovalent multiporphyrin array. AB - Excitation of the peripheral Zn porphyrin units in a noncovalent five-porphyrin array, formed by gable-like zinc(II) bisporphyrins and a central free-base meso tetrakis(4-pyridyl)porphyrin in a 2:1 ratio, (ZnP(2))(2).(TPyP), does not lead to a quantitative sensitization of the luminescence of the free-base porphyrin acceptor, even though there is an effective energy transfer. Time resolution of the luminescence evidences a quenching of TPyP upon sensitization by the peripheral ZnP(2). The time evolution of the TPyP fluorescence in the complex can be described by a bi-exponential fitting with a major component of 180 ps and a minor one of 5 ns, compared to an isolated TPyP lifetime of 9.4 ns. The two quenched lifetimes are shown to be correlated to the presence of 2:1 and 1:1 complexes, respectively. No quenching of TPyP fluorescence occurs in (ZnP(2))(2).(TPyP) at 77 K in a rigid solvent for which only an energy-transfer process (tau=150+/-10 ps) from peripheral ZnP(2) to the central TPyP is observed. An unusual HOMO-HOMO electron-transfer reaction from ZnP(2) to the excited TPyP units, responsible for the observed phenomena, is detected. The resulting charge separated state, (ZnP(2))(+)(2).(TPyP)(-) is found to recombine to the ground state with a lifetime of 11 ns. PMID- 20589847 TI - The trans influence in the modulation of platinum anticancer agent biology: the effect of nitrite leaving group on aquation, reactions with S-nucleophiles and DNA binding of dinuclear and trinuclear compounds. AB - To examine the effect of leaving group and trans influence on the general reactivity of polynuclear platinum antitumor agents we investigated substitution of the chloride leaving groups with nitrite ion, which forms strong bonds to Pt. It was of interest to explore whether nitrite could be used to modulate biological properties of these agents, in particular the deactivating reactions that occur on reaction with S-nucleophiles, involving loss of the linking diamine under the trans influence of sulfur. Reported herein is a study of the synthesis, aquation, DNA binding and reactions with glutathione (GSH), methionine (Met) and acetylmethione (AcMet) of nitrito derivatives of di- and trinuclear platinum antitumor compounds: [{trans-PtNO(2)(NH(3))(2)}(2)(mu NH(2)(CH(2))(6)NH(2))](NO(3))(2) (1-NO(2)) and [{trans-PtNO(2)(NH(3))(2)}(2)(mu trans-Pt(NH(3))(2){NH(2)(CH(2))(6)NH(2)}(2))](NO(3))(4) (1'-NO(2)). {(1)H,(15)N} HSQC NMR studies revealed that 1-NO(2) is inert to aquation reactions, even after prolonged incubation at physiological pH. Monitoring of the interaction of 1 NO(2) with the duplex 5'-d(ATATGTACATAT)(2) (I) showed only unreacted complex, consistent with activation by aquation being a requirement for covalent DNA binding. The reaction of 1-NO(2) with GSH was studied by (1)H, (195)Pt, (15)N and {(1)H,(15)N}-HSQC NMR spectroscopy. For the parent dichlorido compounds (1 and 1') substitution of chloride by GS(-) leads to drug degradation involving liberation of the diamine linker. While the same final products trans [Pt(SG)(2)(NH(3))(2)] (5) and trans-[{Pt(SG)(NH(3))(2)}(2)-mu-SG] (6) are formed, different mechanisms are involved, consistent with the trans influence NO(2)(-) > Cl(-); the half-life is slightly longer for 1-NO(2) (1.8 h) compared with 1 (1.3 h). Identification of the intermediate trans-[Pt(NH(3))(2)(NO(2))(SG)] (4) shows that the nitrito group remains coordinated while the linker amine is substituted by coordination of GS(-), and then trans labilization of the nitrito group occurs leading to 5 and 6. Reaction of the trinuclear 1'-NO(2) with GSH follows essentially the same reaction pathway. Reaction of 1-NO(2) with Met and AcMet is much slower and only 20 % liberated amine was observed after reaction with Met for 24 h at 37 degrees C. The final product from reaction with AcMet is trans [Pt(NH(3))(2)(NO(2))(AcMet)], as in this case coordination of the S-nucleophile does not lead to trans labilization of the nitrito group. PMID- 20589849 TI - Increasing the activity of monoclonal antibody therapeutics by continuous chromatography (MCSGP). AB - The charged monoclonal antibody (mAb) variants of the commercially available therapeutics Avastin(r), Herceptin(r) and Erbitux(r) were separated by ion exchange gradient chromatography in batch and continuous countercurrent mode (MCSGP process). Different stationary phases, buffer conditions and two MCSGP configurations were used in order to demonstrate the broad applicability of MCSGP in the field of charged protein variant separation. Batch chromatography and MCSGP were compared with respect to yield, purity, and productivity. In the case of Herceptin(r), also the biological activity of the product stream was taken into account as performance indicator. The robustness of the MCSGP process against feed composition variations was confirmed experimentally and by model simulations. PMID- 20589850 TI - Design of cellular porous biomaterials for wall shear stress criterion. AB - The microfluidic environment provided by implanted prostheses has a decisive influence on the viability, proliferation and differentiation of cells. In bone tissue engineering, for instance, experiments have confirmed that a certain level of wall shear stress (WSS) is more advantageous to osteoblastic differentiation. This paper proposes a level-set-based topology optimization method to regulate fluidic WSS distribution for design of cellular biomaterials. The topological boundary of fluid phase is represented by a level-set model embedded in a higher dimensional scalar function. WSS is determined by the computational fluid dynamics analysis in the scale of cellular base cells. To achieve a uniform WSS distribution at the solid-fluid interface, the difference between local and target WSS is taken as the design criterion, which determines the speed of the boundary evolution in the level-set model. The examples demonstrate the effectiveness of the presented method and exhibit a considerable potential in the design optimization and fabrication of new prosthetic cellular materials for bioengineering applications. PMID- 20589851 TI - Stoichiometric model and metabolic flux analysis for Leptospirillum ferrooxidans. AB - A metabolic model for Leptospirillum ferrooxidans was developed based on the genomic information of an analogous iron oxidizing bacteria and on the pathways of ferrous iron oxidation, nitrogen and CO(2) assimilation based on experimental evidence for L. ferrooxidans found in the literature. From this metabolic reconstruction, a stoichiometric model was built, which includes 86 reactions describing the main catabolic and anabolic aspects of its metabolism. The model obtained has 2 degrees of freedom, so two external fluxes were estimated to achieve a determined and observable system. By using the external oxygen consumption rate and the generation flux biomass as input data, a metabolic flux map with a distribution of internal fluxes was obtained. The results obtained were verified with experimental data from the literature, achieving a very good prediction of the metabolic behavior of this bacterium at steady state. PMID- 20589852 TI - Polyoxopalladates encapsulating yttrium and lanthanide ions, [X(III)Pd(II)12(AsPh)8O32]5- (X=Y, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu). AB - A series of novel yttrium- and lanthanide-containing heteropolyoxopalladates have been prepared and isolated as hydrated sodium salts, Na(5)[X(III)Pd(II)(12)(AsPh)(8)O(32)]y H(2)O (X=Y (1), Pr (2), Nd (3), Sm (4), Eu (5), Gd (6), Tb (7), Dy (8), Ho (9), Er (10), Tm (11), Yb (12), Lu (13); y=15 27). The polyanions [X(III)Pd(II)(12)(AsPh)(8)O(32)](5-) consist of a cuboid framework of twelve Pd(II) ions with eight phenylarsonate heterogroups located at the vertices and a central guest ion X. The compounds 1-13 have been prepared in a simple one-pot self-assembly reaction of Pd(CH(3)COO)(2), phenylarsonic acid and the respective salt of the element X in 0.5 M aqueous sodium acetate solution (pH 6.9), and characterized in the solid state by single-crystal X-ray diffraction, elemental and thermogravimetric (TGA) analyses, and IR spectroscopy. It was demonstrated that small, medium, and also large lanthanide ions can be incorporated in the center of the novel heteropolypalladate [X(III)Pd(II)(12)(AsPh)(8)O(32)](5-). The Ln-O bond lengths follow the expected trend decreasing from left to right in the lanthanide series. This indicates that the {Pd(II)(12)O(32)} shell can adjust to the coordination requirements of the encapsulated guest cation. Compounds 3 and 5 were selected for electrochemical studies. Their cyclic voltammetry in a lithium acetate buffer at pH 5.9 showed a Pd(0) deposition process on the glassy carbon electrode surface. Coulometry indicated that all Pd(II) centers were reduced to Pd(0). The film was stable and could be taken out of the deposition medium and characterized in pure pH 5.9 buffer. Magnetic susceptibility and EPR measurements were carried out on 5 and 6. The former was confirmed to be diamagnetic and the latter strongly paramagnetic with a S=7/2 ground state. DFT calculations for some of the polyoxometalates have been also performed. PMID- 20589853 TI - Isolation of a zwitterionic dienegold(III) complex intermediate in the direct conversion of enyne-amines to cyclopentadienes. PMID- 20589854 TI - Benzylic boron reagents behaving as allylic boron reagents towards aldehydes: a new asymmetric reaction leading to homoallylic alcohols with concomitant dearomatisation. PMID- 20589855 TI - Experimental and computational studies into an ATPH-promoted exo-selective IMDA reaction: a short total synthesis of Delta9-THC. PMID- 20589856 TI - Challenges to multiple testing in clinical trials. AB - Multiple testing problems are complex in evaluating statistical evidence in pivotal clinical trials for regulatory applications. However, a common practice is to employ a general and rather simple multiple comparison procedure to handle the problems. Applying multiple comparison adjustments is to ensure proper control of type I error rates. However, in many practices, the emphasis of the type I error rate control often leads to a choice of a statistically valid multiple test procedure but the common sense is overlooked. The challenges begin with confusions in defining a relevant family of hypotheses for which the type I error rates need to be properly controlled. Multiple testing problems are in a wide variety, ranging from testing multiple doses and endpoints jointly, composite endpoint, non-inferiority and superiority, to studying time of onset of a treatment effect, and searching for minimum effective dose or a patient subgroup in which the treatment effect lies. To select a valid and sensible multiple test procedure, the first step should be to tailor the selection to the study questions and to the ultimate clinical decision tree. Then evaluation of statistical power performance should come in to play in the next step to fine tune the selected procedure. PMID- 20589857 TI - Optimized sample preparation of endoscopic collected pancreatic fluid for SDS PAGE analysis. AB - The standardization of methods for human body fluid protein isolation is a critical initial step for proteomic analyses aimed to discover clinically relevant biomarkers. Several caveats have hindered pancreatic fluid proteomics, including the heterogeneity of samples and protein degradation. We aim to optimize sample handling of pancreatic fluid that has been collected using a safe and effective endoscopic collection method (endoscopic pancreatic function test). Using SDS-PAGE protein profiling, we investigate (i) precipitation techniques to maximize protein extraction, (ii) auto-digestion of pancreatic fluid following prolonged exposure to a range of temperatures, (iii) effects of multiple freeze thaw cycles on protein stability, and (iv) the utility of protease inhibitors. Our experiments revealed that TCA precipitation resulted in the most efficient extraction of protein from pancreatic fluid of the eight methods we investigated. In addition, our data reveal that although auto-digestion of proteins is prevalent at 23 and 37 degrees C, incubation on ice significantly slows such degradation. Similarly, when the sample is maintained on ice, proteolysis is minimal during multiple freeze-thaw cycles. We have also determined the addition of protease inhibitors to be assay-dependent. Our optimized sample preparation strategy can be applied to future proteomic analyses of pancreatic fluid. PMID- 20589858 TI - Electrophoretically mediated microanalysis for the evaluation of interspecies variation in cholinesterase metabolism. AB - This study describes an electrophoretically mediated microanalysis method, suitable for the preclinical evaluation of the hydrolysis of ester drugs by the serum of different animals and for further characterization of human-animal correlation. Dog, cat, cow, horse, sheep, rat and human serum were diluted (25%) in the appropriate buffer and replaced the enzyme solution usually used in electrophoretically mediated microanalysis methods for the study of enzyme kinetics. They were then compared in terms of the ability to hydrolyze acetylthiocholine and butyrylthiocholine (0.25 mM) by in-capillary reaction. Human serum afforded the highest conversion rates (52% butyryltiocholine and 34% acetylthiocholine) followed by horse (31 and 35%), dog (26 and 24%), cat (22 and 14%), rat (11 and 15%) and sheep (8 and 8%). Hydrolysis by bovine serum was negligible. The method is fast (under 8 min including rinsing steps), sensitive (under 25 microM substrate could be quantified) and repeatable (RSD approximately 2%), only requiring minute amounts of sample. PMID- 20589859 TI - Capillary gel electrophoresis with laser-induced fluorescence of plasmid DNA in untreated capillary. AB - A technique utilizing CGE-LIF in a bare capillary has been developed and evaluated for the detection of the three different topoisomers (linear, open circle, and supercoiled) of plasmid DNA along with the prospect of the dimer form of the supercoiled isoform. Utilizing the zwitterionic buffer, HEPES with boric acid sufficiently prevented capillary wall interactions and minimized the EOF, enabling a well-resolved separation of different plasmid isoforms. Multiple run conditions including buffer concentration and pH, hydroxypropylmethylcellulose size and amount, injection parameters, and the presence of an intercalating dye were evaluated and optimized. In addition, the feasibility of using this method as a platform for varying sizes of plasmid was investigated. PMID- 20589860 TI - Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules. AB - SCOPE: Coffee is among the most frequently consumed beverages. Its consumption is inversely associated to the incidence of diseases related to reactive oxygen species; the phenomenon may be due to its antioxidant properties. Our primary objective was to investigate the impact of consumption of a coffee containing high levels of chlorogenic acids on the oxidation of proteins, DNA and membrane lipids; additionally, other redox biomarkers were monitored in an intervention trial. METHODS AND RESULTS: The treatment group (n=36) consumed instant coffee co extracted from green and roasted beans, whereas the control consumed water (800 mL/P/day, 5 days). A global statistical analysis of four main biomarkers selected as primary outcomes showed that the overall changes are significant. 8 Isoprostaglandin F2alpha in urine declined by 15.3%, 3-nitrotyrosine was decreased by 16.1%, DNA migration due to oxidized purines and pyrimidines was (not significantly) reduced in lymphocytes by 12.5 and 14.1%. Other markers such as the total antioxidant capacity were moderately increased; e.g. LDL and malondialdehyde were shifted towards a non-significant reduction. CONCLUSION: The oxidation of DNA, lipids and proteins associated with the incidence of various diseases and the protection against their oxidative damage may be indicative for beneficial health effects of coffee. PMID- 20589861 TI - Antioxidant effectiveness of coffee extracts and selected constituents in cell free systems and human colon cell lines. AB - SCOPE: Epidemiological studies suggest that coffee can reduce the risk of degenerative diseases such as diabetes type 2, cardiovascular disease and cancer. These beneficial effects have partly been attributed to the antioxidant activity of coffee. We determined composition and antioxidant potential of differentially roasted coffee extracts and investigated the impact of selected original constituents and roast products. METHODS AND RESULTS: Parameters studied were direct antioxidant activity (trolox equivalent antioxidant capacity/oxygen radical absorbing capacity), cellular reactive oxygen species (ROS) level, DNA damage and protein expression of NAD(P)H: quinone oxidoreductase, gamma glutamylcysteine ligase and glutathione reductase in HT-29/Caco-2 cells at 24-h incubation. All extracts showed distinct direct antioxidant activity: medium roasts>light roast AB1 (caffeoylquinic acid (CQA)-rich Arabica Brazil extract); dark roast AB2 (N-methylpyridinium (NMP)-rich Arabica Brazil extract), and diminished t-butylhydroperoxide-induced ROS level in HT-29 cells (AB2>medium roasts>AB1). NAD(P)H:quinone oxidoreductase 1 expression and gamma glutamylcysteine ligase expression were distinctly induced by AB1 and 5-CQA, but not by AB2 and NMP. 5-CQA and caffeic acid exhibited highest trolox equivalent antioxidant capacity/oxygen radical absorbing capacity values (5-CQA: 1.3/3.5 mM and caffeic acid: 1.3/3.9 mM trolox); ROS level was distinctly diminished by 5 CQA (>=3 MUM), catechol (30 MUM) and trigonelline (>=30 MUM), whereas menadione induced DNA damage in Caco-2 cells was reduced by NMP compounds (1-30 MUM). CONCLUSION: The results emphasize that both original constituents and roast products contribute to the cellular antioxidant effectiveness of coffee. PMID- 20589867 TI - A sensitive and specific enzyme-linked immunosorbent assay for the detection of lincomycin in food samples. AB - BACKGROUND: Lincomycin (LIN) is an antibiotic widely used in veterinary medicine to cure infections caused by Gram-positive pathogens. Although the toxicity of LIN is not serious, it will cause adverse effects in humans, such as pseudomembranous enteritis and bacterial resistance. In this study, for the preparation of a LIN derivative, a novel modification method was adopted. The LIN derivative modified at 2-position with a carboxylic group at the end of the spacer was synthesised and coupled to carrier proteins. A LIN polyclonal antibody based enzyme-linked immunosorbent assay (ELISA) was developed and characterised. RESULTS: The ELISA standard curve was constructed with concentrations of 0.1-1000 ng mL(-1). The IC(50) value for nine standard curves was in the range 23.7-29.3 ng mL(-1) and the limit of detection at a signal-to-noise ratio of 3 was 0.15 0.98 ng mL(-1). The cross-reactivity value of the LIN antibody with clindamycin hydrochloride, a homologue of LIN with similar molecular structure, was 18.9%, while less than 0.1% cross-reactivity was found with seven other compounds. For LIN-spiked food samples, the recoveries and relative standard deviation (RSD) were 76.6-117.6% and 1.7-34.6%, respectively. CONCLUSION: The proposed ELISA can be utilised as a sensitive and specific analytical tool for the detection of LIN in food samples. PMID- 20589866 TI - Definition and classification of hyperkinetic movements in childhood. AB - Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials. PMID- 20589868 TI - Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. AB - A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains "global cognitive functioning," "memory," "working memory," "attention," and "executive function." These domain-specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN-DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa-equivalence dosage (LED) and axial subscore of the UPDRS in the off-medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN-DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN-DBS. PMID- 20589869 TI - Sensory alien hand syndrome in corticobasal degeneration: a cerebral blood flow study. AB - The presence of alien hand syndrome (AHS) is suggestive of the diagnosis of corticobasal degeneration when it develops in a progressive way. Sensory AHS (sAHS) should be distinguished from the motor form described more commonly. The physiopathology of sAHS remains unclear. The aim of this study is to determine cerebral regions involved in sAHS. We compared perfusion single photon emission computer tomography scans of patients with sAHS (n = 3) and without (n = 4). We observed significant decrease of regional cerebral blood flow over the nondominant thalamus in sAHS+ compared to sAHS- patients. This result suggests the involvement of the nondominant thalamus in sAHS. PMID- 20589870 TI - Differential pattern of brain-specific CSF proteins tau and amyloid-beta in Parkinsonian syndromes. AB - To evaluate cerebrospinal fluid (CSF) proteins reflecting processes of neurodegeneration and glial activation in progressive supranuclear palsy (PSP; Richardson's syndrome, n = 20; PSP-Parkinsonism, n = 7) and multiple system atrophy (MSA, n = 25), we analyzed tau, phosphorylated tau, amyloid-beta(1-42) (Abeta1-42), Abeta1-40, glial fibrillary acidic protein (GFAP), and CSF routine variables. Individuals with PSP-Parkinsonism and MSA had elevated tau levels when compared with Richardson's syndrome, Parkinson's disease (PD), and age-matched controls (P or=65 CAG repeats showed a more severe long-term disability and a poorer prognosis. In contrast, the rate of progression after the onset did not correlate with CAG repeat length. The CAG repeat length may have a considerable effect on not only the disease onset but also the disease milestones and prognosis in DRPLA patients. These effects of CAG repeat length may be relevant in designing future clinical therapeutic trials. PMID- 20589873 TI - Parkinson's disease rehabilitation: a pilot study with 1 year follow up. PMID- 20589874 TI - Brain interstitial nociceptin/orphanin FQ levels are elevated in Parkinson's disease. AB - Expression and release of nociceptin/orphanin FQ (N/OFQ) are elevated in the substantia nigra reticulata of 6-hydroxydopamine-hemilesioned rats, suggesting a pathogenic role for N/OFQ in Parkinson's disease. In this study, we investigated whether elevation of N/OFQ expression in 6-hydroxydopamine-hemilesioned rats selectively occurs in substantia nigra and whether hypomotility following acute haloperidol administration is accompanied by a rise in nigral N/OFQ levels. Moreover, to prove a link between N/OFQ and idiopathic Parkinson's disease in humans, we measured N/OFQ levels in the cerebrospinal fluid of parkinsonian patients undergoing surgery for deep brain stimulation. In situ hybridization demonstrated that dopamine depletion was associated with increase of N/OFQ expression in substantia nigra (compacta +160%, reticulata +105%) and subthalamic nucleus (+45%), as well as reduction in caudate putamen (-20%). No change was observed in globus pallidus, nucleus accumbens, thalamus, and motor cortex. Microdialysis coupled to the bar test allowed to demonstrate that acute administration of haloperidol (0.8 and 3 mg/kg) increased nigral N/OFQ levels (maximally of +47% and +53%, respectively) in parallel with akinesia. A correlation with preclinical studies was found by analyzing N/OFQ levels in humans. Indeed, N/OFQ levels were found to be approximately 3.5-fold elevated in the cerebrospinal fluid of parkinsonian patients (148 fmol/ml) compared with nonparkinsonian neurologic controls (41 fmol/ml). These data represent the first clinical evidence linking N/OFQ to idiopathic Parkinson's disease in humans. They strengthen the pathogenic role of N/OFQ in the modulation of parkinsonism across species and provide a rationale for developing N/OFQ receptor antagonists as antiparkinsonian drugs. PMID- 20589876 TI - Long-term suppression of Meige syndrome after pallidal stimulation: a 10-year follow-up study. PMID- 20589875 TI - Treatment of insomnia in Parkinson's disease: a controlled trial of eszopiclone and placebo. AB - Parkinson's disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Sleep disturbances, typically in sleep maintenance, are found in up to 88% of these individuals and are associated with a variety of poor outcomes. Despite being common and important, there are few data to guide clinical care. We conducted a 6-week, randomized, controlled trial of eszopiclone and placebo in 30 patients with PD and insomnia. Patients with other primary sleep disorders (PSG defined) were excluded. The primary outcome was total sleep time (TST), and secondary measures included wake after sleep onset (WASO), number of awakenings, and quality of sleep, among others. The groups did not significantly differ on TST, but significant differences, favoring eszopiclone, did emerge in number of awakenings (P = 0.035), quality of sleep (P = 0.018), and in physician-rated CGI improvement (P = 0.035). There was also a trend toward significance in WASO (P = 0.071). There were no significant differences between groups in measures of daytime functioning. The drug was well tolerated, with 33% of patients on eszopiclone and 27% of patients on placebo reporting adverse events. Although modest in size, this is the first controlled study of the treatment of insomnia in patients with PD. Eszopiclone did not increase TST significantly but was superior to placebo in improving quality of sleep and some measures of sleep maintenance, which is the most common sleep difficulty experienced by patients with PD. Definitive trials of the treatment of sleep disorders in this population are warranted. PMID- 20589877 TI - Chylomicron retention disease: dystonia as a new clinical feature. PMID- 20589878 TI - Refractory head movements secondary to Sandifer syndrome treated with enteral feeding. PMID- 20589879 TI - Decreased ventral striatal activity with impulse control disorders in Parkinson's disease. AB - A range of impulse control disorders (ICDs) are reported to occur in Parkinson's disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. We used both arterial spin labeling perfusion functional magnetic resonance imaging (fMRI) to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Eighteen PD patients, either with a diagnosis of one or more ICDs (N = 9) or no lifetime ICD history (N = 9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs. PMID- 20589881 TI - A case-control study of the effects of pregnancy planning on neural tube defects and its primary preventive measures. AB - BACKGROUND: Measures for prevention of neural tube defects (NTDs) have been recommended for many years in China, but the compliance with these measures is unsatisfactory. This study aims to compare the effect differences between planned pregnancy and unplanned pregnancy in the compliance with these measures and analyze the interactions between pregnancy planning and these measures for NTD prevention. METHODS: A 1:1 matched case-control study was conducted. We randomly selected 349 women who delivered or gestated babies/fetuses with NTDs in the last two years in two provinces and matched them with 349 women who delivered babies without obvious birth defects as controls. RESULTS: In the case group, 99 women reported that they had planned their pregnancies, accounting for 28.4%, and the proportion who received preconception examinations and took folic acid prior to conception was 13.8 and 8.6%, respectively. According to the multivariate analysis, health education (odds ratio [OR], 0.350), preconception examinations (OR, 0.497) and folic acid consumption prior to conception (OR, 0.257) all had preventative effects on NTDs (for all, p < 0.05). In both groups, the proportions of women who received preconception examinations and reported folic acid intake were much higher for those who reported planning their pregnancies compared to women with an unplanned pregnancy (for all, p < 0.01); and for NTD prevention, synergistic interactions existed between pregnancy planning and the other preventive measures. CONCLUSION: Folic acid consumption prior to conception, preconception examinations, and health education have preventive effects on NTDs. Pregnancy planning can significantly promote compliance with these preventive behaviors. In addition, there are synergistic interactions between pregnancy planning and these measures. PMID- 20589880 TI - Neural tube defects induced by folate deficiency in mutant curly tail (Grhl3) embryos are associated with alteration in folate one-carbon metabolism but are unlikely to result from diminished methylation. AB - BACKGROUND: Folate one-carbon metabolism has been implicated as a determinant of susceptibility to neural tube defects (NTDs), owing to the preventive effect of maternal folic acid supplementation and the higher risk associated with markers of diminished folate status. METHODS: Folate one-carbon metabolism was compared in curly tail (ct/ct) and genetically matched congenic (+(ct)/+(ct)) mouse strains using the deoxyuridine suppression test in embryonic fibroblast cells and by quantifying s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH) in embryos using liquid chromatography tandem mass spectrometry. A possible genetic interaction between curly tail and a null allele of 5,10 methylenetetrahydrofolate reductase (MTHFR) was investigated by generation of compound mutant embryos. RESULTS: There was no deficit in thymidylate biosynthesis in ct/ct cells, but incorporation of exogenous thymidine was lower than in +(ct)/+(ct) cells. In +(ct)/+(ct) embryos the SAM/SAH ratio was diminished by dietary folate deficiency and normalized by folic acid or myo inositol treatment, in association with prevention of NTDs. In contrast, folate deficiency caused a significant increase in the SAM/SAH ratio in ct/ct embryos. Loss of MTHFR function in curly tail embryos significantly reduced the SAM/SAH ratio but did not cause cranial NTDs or alter the frequency of caudal NTDs. CONCLUSIONS: Curly tail fibroblasts and embryos, in which Grhl3 expression is reduced, display alterations in one-carbon metabolism, particularly in the response to folate deficiency, compared to genetically matched congenic controls in which Grhl3 is unaffected. However, unlike folate deficiency, diminished methylation potential appears to be insufficient to cause cranial NTDs in the curly tail strain, nor does it increase the frequency of caudal NTDs. PMID- 20589882 TI - Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors. AB - BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex. METHODS: Gene-trap mutation Cecr2(Gt45Bic) results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11-14 somites stage Cecr2(Gt45Bic)embryos. RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2(Gt45Bic) embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only approximately 7- to 14-fold from normal levels, suggesting the Cecr2(Gt45Bic) is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2 (tm1.1Hemc)). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2(Gt45Bic) in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2(tm1.1Hemc) line. Subsequent qRT-PCR using Cecr2 (tm1.1Hemc) mutant heads confirmed downregulation of transcription factors Alx1/Cart1, Dlx5, Eya1, and Six1. CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2. PMID- 20589884 TI - Mosaic expression of Med12 in female mice leads to exencephaly, spina bifida, and craniorachischisis. AB - BACKGROUND: A precise temporal and spatial regulation of gene expression is necessary to achieve neural tube closure. Med12, a subunit of the mediator complex, can bind transcription factors and modulate expression of their target genes. Med12 is essential during early mouse development and is important for neural tube closure. METHODS: We have made use of a mouse line carrying a conditional null allele of the X-linked Med12 gene to generate heterozygous female embryos that express Med12 in a mosaic fashion thus allowing the study of the role of Med12 during neural tube closure. RESULTS: Mosaic expression of Med12 causes a wide variety of embryonic phenotypes. Some embryos were unable to complete turning and were found with arrested development at embryonic day (ED) 9.5. Others were able to pass ED 12.5 and displayed defects in neural tube closure. These defects included exencephaly, spina bifida, craniorachischisis, split face, and curly tail. Histologic and skeletal analyses of these mutant females show that the neural plate is unable to elevate and is completely flat in the regions of the body axis where neural tube closure fails. CONCLUSIONS: We report examples of all known neural tube defects implying Med12 in the full process of neural tube closure along the complete body axis. Our work points to Med12 being an essential coregulator of transcription factors controlling neural tube closure. PMID- 20589883 TI - Developmental microRNA expression profiling of murine embryonic orofacial tissue. AB - BACKGROUND: Orofacial development is a multifaceted process involving precise, spatio-temporal expression of a panoply of genes. MicroRNAs (miRNAs), the largest family of noncoding RNAs involved in gene silencing, represent critical regulators of cell and tissue differentiation. MicroRNA gene expression profiling is an effective means of acquiring novel and valuable information regarding the expression and regulation of genes, under the control of miRNA, involved in mammalian orofacial development. METHODS: To identify differentially expressed miRNAs during mammalian orofacial ontogenesis, miRNA expression profiles from gestation day (GD) -12, -13 and -14 murine orofacial tissue were compared utilizing miRXplore microarrays from Miltenyi Biotech. Quantitative real-time PCR was utilized for validation of gene expression changes. Cluster analysis of the microarray data was conducted with the clValid R package and the UPGMA clustering method. Functional relationships between selected miRNAs were investigated using Ingenuity Pathway Analysis. RESULTS: Expression of over 26% of the 588 murine miRNA genes examined was detected in murine orofacial tissues from GD-12-GD-14. Among these expressed genes, several clusters were seen to be developmentally regulated. Differential expression of miRNAs within such clusters wereshown to target genes encoding proteins involved in cell proliferation, cell adhesion, differentiation, apoptosis and epithelial-mesenchymal transformation, all processes critical for normal orofacial development. CONCLUSIONS: Using miRNA microarray technology, unique gene expression signatures of hundreds of miRNAs in embryonic orofacial tissue were defined. Gene targeting and functional analysis revealed that the expression of numerous protein-encoding genes, crucial to normal orofacial ontogeny, may be regulated by specific miRNAs. PMID- 20589885 TI - Increased voluntary drive is associated with changes in common oscillations from 13 to 60 Hz of interference but not rectified electromyography. AB - The purpose of this study was to compare the capability of interference and rectified electromyography (EMG) to detect changes in the beta (13-30-HZ) and Piper (30-60-HZ) bands when voluntary force is increased. Twenty adults exerted a constant force abduction of the index finger at 15% and 50% of maximum. The common oscillations at various frequency bands (0-500 HZ) were estimated from the first dorsal interosseous muscle using cross wavelets of interference and rectified EMG. For the interference EMG signals, normalized power significantly (P < 0.01) increased with force in the beta (9.0 +/- 0.9 vs. 15.5 +/- 2.1%) and Piper (13.6 +/- 0.9 vs. 21 +/- 1.7%) bands. For rectified EMG signals, however, the beta and Piper bands remained unchanged (P > 0.4). Although rectified EMG is used in many clinical studies to identify changes in the oscillatory drive to the muscle, our findings suggest that only interference EMG can accurately capture the increase in oscillatory drive from 13 to 60 HZ with voluntary force. PMID- 20589886 TI - INa and IKir are reduced in Type 1 hypokalemic and thyrotoxic periodic paralysis. AB - We evaluated voltage-gated Na(+) (I(Na)) and inward rectifier K(+) (I(Kir)) currents and Na(+) conductance (G(Na)) in patients with Type 1 hypokalemic (HOPP) and thyrotoxic periodic paralysis (TPP). We studied intercostal muscle fibers from five subjects with HOPP and one with TPP. TPP was studied when the patient was thyrotoxic (T-toxic) and euthyroid. We measured: (1) I(Kir), (2) action potential thresholds, (3) I(Na), (4) G(Na), (5) intracellular [Ca(2+)], and (6) histochemical fiber type. HOPP fibers had lower I(Na), G(Na), and I(Kir) and increased action potential thresholds. Paralytic attack frequency correlated with the action potential threshold, G(Na) and I(Na), but not with I(Kir). G(Na), I(Na), and [Ca(2+)] varied with fiber type. HOPP fibers had increased [Ca(2+)]. The subject with TPP had values for G(Na), I(Na), action potential threshold, I(Kir), and [Ca(2+)] that were similar to HOPP when T-toxic and to controls when euthyroid. HOPP T-toxic TPP fibers had altered G(Na), I(Na), and I(Kir) associated with elevation in [Ca(2+)]. PMID- 20589887 TI - Intraoperative on-nerve nerve conduction study and conversion factor in the sural nerve. AB - To determine the conversion factor (CF) of the sural nerve the correlation between the maximum nerve conduction velocity (NCV) and the diameter of the largest fibers was studied in 30 patients suspected of having neuropathy. Sensory nerve action potentials were obtained by on-nerve needle nerve conduction study using needle electrodes placed on the exposed sural nerve during biopsy. The CF was 4.3 (n = 2) in normal sural nerves and close to the normal value (3.85, n = 4) in axonal neuropathy. The CF in demyelinating neuropathy was smaller than the normal value (2.77, n = 24), indicating disproportionately slower conduction than expected from the diameter of nerve fibers. The CF was helpful in differentiating between demyelinating and axonal neuropathies. We propose that a 36% decrease from the mean value of NCV is a reasonable criterion for demyelination of the nerve. PMID- 20589888 TI - Motor unit number index (MUNIX): a novel neurophysiological technique to follow disease progression in amyotrophic lateral sclerosis. AB - Motor unit number estimation techniques in amyotrophic lateral sclerosis (ALS) patients are technically challenging and time-consuming. The Motor Unit Number Index (MUNIX) is a novel technique based on surface-EMG recordings and requires only 3-5 minutes per muscle. The objective was to explore the feasibility of longitudinal MUNIX measurements in ALS patients. In seven patients enrolled in a clinical trial, eight muscles were studied every 2 months for up to 15 months in addition to the revised ALS-functional rating scale, slow vital capacity, and compound muscle action potentials. The method was well tolerated and easy to perform. Initial MUNIX measures were significantly reduced compared to controls (487 +/- 194 vs. 1459 +/- 113; P < 0.001). Relative drop from baseline paralleled the clinical course and was greater than the drop of other markers of disease progression. MUNIX measurements in multiple muscles are suitable for serial neurophysiologic investigations in ALS. Further longitudinal data are needed for reliability validation. PMID- 20589889 TI - Corticospinal tract dysfunction and development of amyotrophic lateral sclerosis following electrical injury. AB - The causal relationship between electrical injury and development of amyotrophic lateral sclerosis (ALS) remains controversial. We describe the case of a 25-year old man who developed ALS after a severe electrical injury. Cerebral magnetic resonance imaging (MRI) demonstrated hyperintensities involving the corticospinal tract. Functional testing with transcranial magnetic stimulation established that the motor cortex was relatively inexcitable. In addition, there were features of denervation on electromyography and muscle biopsy that supported concomitant lower motor neuron findings and the diagnosis of ALS. PMID- 20589890 TI - Clinical and electrophysiological features of the 2007 Guillain-Barre syndrome epidemic in northeast China. AB - Guillain-Barre syndrome (GBS) generally presents sporadically. Epidemics of GBS are unusual. We reviewed the medical records of 26 patients hospitalized for GBS during the 2007 GBS epidemic in northeast China. The objective was to determine whether there were clinical and electrophysiological characteristics. All patients had drunk unboiled water, and the illness was preceded by diarrhea in 19 (73%) patients. Only 1 patient had a Campylobacter jejuni infection, whereas 14 (54%) patients exhibited features of acute motor axonal neuropathy (AMAN). The most common electrophysiological findings in early GBS included decreased compound muscle action potential (CMAP) amplitude (62%), abnormal F waves (73%), and abnormal H reflexes (62%). This epidemic of GBS appears to have been associated with consumption of contaminated water. The main subtype was AMAN, which was associated with a longer duration of illness and a worse prognosis. Electrodiagnostic evaluations are helpful for diagnosis in the primary stages of GBS. PMID- 20589891 TI - Atypical childhood chronic inflammatory demyelinating polyneuropathy. AB - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon cause of progressive weakness in childhood. The diagnosis is easy when the clinical history and findings are supported by unequivocal electrophysiologic and laboratory evidence of demyelination, but it can be challenging if the criteria for demyelination are not met. We report a case of atypical childhood CIDP to highlight the diagnostic difficulties and the importance of recognizing this treatable condition. PMID- 20589892 TI - Self-reported follow-up post-intervention adherence to resistance exercise training in Charcot-Marie-Tooth disease patients. PMID- 20589893 TI - Fibrosis inhibition and muscle histopathology improvement in laminin-alpha2 deficient mice. AB - In muscular dystrophies (MD) the loss of muscle and its ability to function are associated with fibrosis. We evaluated the efficacy of halofuginone in reducing fibrosis in the dy(2J)/dy(2J) mouse model of congenital MD. Mice were injected intraperitoneally with 5 microg of halofuginone 3 times a week for 5 or 15 weeks, starting at the age of 3 weeks. Halofuginone caused a reduction in collagen synthesis in hindlimb muscles. This was associated with reductions in the degenerated area, in cell proliferation, in the number of myofibers with central nuclei, with increased myofiber diameter, and with enhanced motor coordination and balance. Halofuginone caused a reduction in infiltrating fibroblasts that were located close to centrally nucleated myofibers. Our results suggest that halofuginone reduced the deleterious effects of fibrosis, thus improving muscle integrity. Halofuginone meets the criteria for a novel antifibrotic therapy for MD patients. PMID- 20589894 TI - Timeline of cardiac dystrophy in 3-18-month-old MDX mice. AB - The dystrophin-deficient (mdx) mouse remains the most commonly used model for Duchenne muscular dystrophy (DMD). Mdx mice show a predominantly covert cardiomyopathy, the hallmark of which is fibrosis. We compared mdx and normal mice at six ages (3, 6, 9, 12, 15, and 18 months) using in vivo assessment of cardiac function, selective collagen staining, and measures of TGF-beta mRNA, Evans blue dye infiltration, macrophage infiltration, and aortic wall thickness. Clear temporal progression was demonstrated, including early fragility of cardiomyocyte membranes, which has an unrelated impact on cardiac function but is associated with macrophage infiltration and fibrosis. Aortic wall thickness is less in older mdx mice. Mdx mice display impaired responses to inotropic challenge from a young age; this is indicative of altered adrenoreceptor function. We draw attention to the paradox of ongoing fibrosis in mdx hearts without a strong molecular signature (in the form of TGF-beta mRNA expression). PMID- 20589895 TI - Inverse correlation between VEGF and soluble VEGF receptor 2 in POEMS with AIDP responsive to intravenous immunoglobulin. AB - POEMS (polyneuropathy, organomegaly, endocrinopathy, M-band, and skin changes) syndrome is characterized by chronic progressive polyneuropathy and plasma-cell dyscrasia. A major diagnostic criterion of POEMS is elevation of circulating vascular endothelial growth factor (VEGF), which is believed to play a pathogenic role in this disease. We report a case of POEMS that presented as relapsing acute inflammatory demyelinating polyneuropathy, in which complete remission after intravenous immunoglobulin (IVIg) treatment was unexpectedly observed. At clinical nadir, the VEGF level was 30-fold higher, and the soluble form of VEGF receptor 2 (sVEGFR2), which acts as a decoy for VEGF, was 2.7-fold lower than normal. These changes combined might contribute to the pathogenesis of POEMS, inducing vascular permeability and tissue edema. At 9-month follow-up, during clinical remission, VEGF and sVEGFR2 were near normal values. sVEGFR2 reduction is a new finding in POEMS. IVIg treatment may benefit POEMS patients with acute neuropathy by downgrading VEGF release induced by inflammatory cytokines. PMID- 20589896 TI - Effect of electromyostimulation on apoptosis-related factors in denervation and reinnervation of rat skeletal muscles. AB - Electromyostimulation (EMS) has been utilized to reduce muscle atrophy, but its effect on denervated muscles is controversial. This study was performed to determine the effect of EMS on intramuscular changes and apoptosis during denervation and reinnervation following nerve damage. Rat sciatic nerves were denervated completely (CD) or partially (PD), and EMS was applied for 2 weeks. The same numbers of cases were followed without EMS. Nerve conduction studies, muscle weights, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measure apoptotic changes, and Western blot were done 4, 8, and 12 weeks after injury. TUNEL-positive nuclei of CD muscles (18.6 +/- 5.5%) were more prevalent than those of PD muscles (7.5 +/- 3.3%). The EMS group showed greater muscle weight, fewer positive nuclei (4.7 +/- 1.9%), and lower BAX and Bcl-2 expression levels compared with the non-EMS group at 4 weeks after PD but not after CD. Denervated muscle atrophy delayed by EMS may be linked with enhanced anti-apoptosis under the control of apoptosis-related factors. PMID- 20589897 TI - Good nutritional control may prevent polyneuropathy after bariatric surgery. AB - Previously we showed that peripheral neuropathy occurs after bariatric surgery and was associated with malnutrition (mainly sensory polyneuropathy). This study asks whether a multidisciplinary approach to bariatric surgery lowers risk for developing peripheral neuropathy. We performed a retrospective cohort study of all patients with bariatric surgery at the Mayo Clinic between 1985 and 2002. Patients underwent intensive nutritional management before and after surgery. Potential risk factors were analyzed using life-table methods (Cox regression). Univariate analysis showed the following risk factors: increased serum glycosylated hemoglobin and triglycerides, prolonged hospitalization, postoperative gastrointestinal symptoms, and nausea and vomiting. Peripheral neuropathy occurred less frequently (7% vs. 13%, P < 0.01) and specifically the sensory polyneuropathy subtype (1% vs. 7%, P < 0.0001) than in our prior cohort. A systematic, multidisciplinary approach of intensive nutritional management before and after surgery with frequent follow-up greatly decreased development of peripheral neuropathy (especially sensory polyneuropathy) in patients receiving bariatric surgery. PMID- 20589898 TI - Development of bladder dysfunction in a rat model of dopaminergic brain lesion. AB - AIMS: Parkinson's disease (PD) is one of the most common neurological disorders causing lower urinary tract dysfunction. We evaluated the temporal development of bladder dysfunction in rat PD model where urodynamic changes were induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). METHODS: Female Sprague-Dawley rats underwent a unilateral stereotaxic injection of 6-OHDA or vehicle (sham group) into the MFB. Cystometry was performed in conscious animals at 3, 14, and 28 days after the injury. Aged matched unlesioned rats were used as healthy controls. RESULTS: Three days after lesion 6-OHDA rats showed higher threshold (TP), maximum pressures (MP), and spontaneous activity (SA) compared to healthy controls. Sham animals exhibited higher TP. After 14 days 6-OHDA rats had also higher micturition frequency, decreased bladder capacity, micturition volume and bladder compliance (Bcom) compared to sham and healthy controls. Sham animals showed lower Bcom and higher MP and SA. After 28 days, 6-OHDA rats exhibited the same changes as those in 14 days, while sham-operated animals showed parameters similar to those in healthy controls. CONCLUSIONS: These findings suggest that 6-OHDA lesion of the MFB causes bladder dysfunction already after 3 days. A pattern of detrusor overactivity was more clearly defined 14 days after the injection and persisted for 28 days. Cystometry may be a useful tool to study the pathophysiology of bladder dysfunction in PD, and urodynamic parameters may possibly be used to evaluate the effects of therapeutic interventions. PMID- 20589899 TI - Re: Genome-based expression profiling study following spinal cord injury in the rat: An array of 48-gene model. PMID- 20589900 TI - Network structure of projections extending from peripheral neurons in the tunic of ascidian larva. AB - In ascidian Ciona intestinalis, a subset of trunk epidermal neurons were shown to possess external network of neural projections. To characterize a more complete network in naturally hatched (chorionated) larvae, we visualized the structure with a confocal laser scanning microscope. High resolution images revealed the huge network consisting of several subnetworks in whole-larval tunic. We named this network the ASNET (ascidian dendritic network in tunic). The ASNET was dynamically generated and collapsed during larval stages. Interestingly, one of the subnetworks found around apical trunk epidermal neurons was bilaterally asymmetric. In caudal epidermal neurons, transmission electron microscopy revealed that 9+2 axonemes were accompanied by a vesicle-containing mass in the ASNET arbor, but the distal end of the arbor contained only the vesicle containing fibrous mass and no 9+2 axonemes. The characteristics of the ASNET suggest that it forms a unique outer body network in the ascidian larval tunic. PMID- 20589901 TI - Identification of genes controlled by LMX1B in E13.5 mouse limbs. AB - During limb development, the dorsal limb mesenchyme expression of the transcription factor LMX1B is required for dorsoventral limb patterning. In mice, Lmx1b mutations result in the mirror-image duplication of ventral limb structures and loss of dorsal limb structures. Heterozygous LMX1B mutations in humans cause the Nail-Patella Syndrome characterized by limb, kidney, and eye developmental defects. We used DNA microarrays to compare the mRNAs in E13.5 mouse Lmx1b mutant and wild-type limbs. We report 14 genes that require Lmx1b for their normal expression in the dorsal limb or the restriction of their expression to the ventral limb. PMID- 20589902 TI - Effects of thoracic epidural analgesia on lower urinary tract function in women. AB - AIMS: The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4-T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies. METHODS: In 13 women with no preoperative lower urinary tract symptoms undergoing open kidney surgery by lumbotomy under TEA, we prospectively assessed changes in urodynamic parameters the day before and 2-3 days after surgery with the patients under TEA. RESULTS: Before versus during TEA, there was a significant increase in postvoid residual (median, 5 ml vs. 220 ml, P<0.001) and a significant decrease in maximum detrusor pressure (median, 23 cmH(2) O vs. 5 cmH(2) O, P=0.001), detrusor pressure at maximum flow rate (median, 18 cmH(2) O vs. 5 cmH(2) O, P=0.001), maximum flow rate (median, 12 ml/sec vs. 3 ml/sec, P<0.001), and voided volume (median, 250 ml vs. 40 ml, P<0.001). In addition, maximum urethral closure pressure at rest decreased significantly under TEA from median 75 cmH(2) O to 56 cmH(2) O (P=0.002). Bladder sensation, maximum cystometric capacity, compliance, and functional profile length at rest were not influenced by TEA. CONCLUSIONS: TEA has a significant effect on bladder emptying with clinically relevant postvoid residual (PVR) necessitating (indwelling or intermittent) catheterization or monitoring of PVR. PMID- 20589903 TI - A pilot study of botulinum toxin for interstitial cystitis/painful bladder syndrome. AB - OBJECTIVES: Preliminary studies using botulinum toxin (BTX) have demonstrated some benefits in treating interstitial cystitis (IC)/painful bladder syndrome (PBS) pain. The purpose of this study was to investigate the efficacy of a periurethral injection of BTX to block urethral visceral and somatic afferent fibers, for the treatment of IC/PBS. METHODS: Twenty adult women with IC/PBS were identified from the Female Urology Clinic at our hospital. Symptom evaluation was performed using a female modification of the Chronic Prostatitis Symptom Index (CPSI), AUA Symptom Index, Graded Chronic Pain Scale, Perceived Stress Scale, and symptom improvement Visual Analog Scale (VAS). All patients were randomized to receive either botulinum toxin A (BTX-A) or placebo (normal saline). Patients randomized to BTX-A received 50 U diluted in 2 cm(3) normal saline injected periurethrally. The physician and patient were blinded to the treatment. RESULTS: BTX was administered to nine women. There were no complications or side effects reported. There was no improvement between placebo and BTX-A groups in the CPSI score at 3-month follow-up (P=0.97). Additionally, there were no improvements in the other symptom indices. At follow-up, the mean VAS for the BTX group was -0.3, indicating the subjects' symptoms were the same as at the start of the study. CONCLUSIONS: Periurethral injection of botulinum toxin in women did not effectively treat the pain of IC/PBS. While the results from this study are negative, there is still a valid rationale for further investigations of novel injection protocols given the dearth of current effective treatments. PMID- 20589904 TI - Domain motion and interdomain hot spots in a multidomain enzyme. AB - The aim of this article is to analyze conformational changes by comparing 10 different structures of Pseudomonas aeruginosa phosphomannomutase/phosphoglucomutase (PMM/PGM), a four-domain enzyme in which both substrate binding and catalysis require substantial movement of the C terminal domain. We focus on changes in interdomain and active site crevices using a method called computational solvent mapping rather than superimposing the structures. The method places molecular probes (i.e., small organic molecules containing various functional groups) around the protein to find hot spots. One of the most important hot spots is in the active site, consistent with the ability of the enzyme to bind both glucose and mannose phosphosugar substrates. The protein has eight additional hot spots at domain-domain interfaces and hinge regions. The locations and nature of six of these hot spots vary between the open, half-open, and closed conformers of the enzyme, in good agreement with the ligand-induced conformational changes. In the closed structures the number of probe clusters at the hinge region significantly depends on the position of the phosphorylated oxygen in the substrate (e.g., glucose 1-phosphate versus glucose 6-phosphate), but the protein remains almost unchanged in terms of the overall RMSD, indicating that computational solvent mapping is a more sensitive approach to detect changes in binding sites and interdomain crevices. Focusing on multidomain proteins we show that the subresolution conformational differences revealed by the mapping are in fact significant, and present a general statistical method of analysis to determine the significance of rigid body domain movements in X-ray structures. PMID- 20589905 TI - Three-dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping. AB - The traditional NMR-based method for determining oligomeric protein structure usually involves distinguishing and assigning intra- and intersubunit NOEs. This task becomes challenging when determining symmetric homo-dimer structures because NOE cross-peaks from a given pair of protons occur at the same position whether intra- or intersubunit in origin. While there are isotope-filtering strategies for distinguishing intra from intermolecular NOE interactions in these cases, they are laborious and often prove ineffectual in cases of weak dimers, where observation of intermolecular NOEs is rare. Here, we present an efficient procedure for weak dimer structure determination based on residual dipolar couplings (RDCs), chemical shift changes upon dilution, and paramagnetic surface perturbations. This procedure is applied to the Northeast Structural Genomics Consortium protein target, SeR13, a negatively charged Staphylococcus epidermidis dimeric protein (K(d) 3.4 +/- 1.4 mM) composed of 86 amino acids. A structure determination for the monomeric form using traditional NMR methods is presented, followed by a dimer structure determination using docking under orientation constraints from RDCs data, and scoring under residue pair potentials and shape based predictions of RDCs. Validation using paramagnetic surface perturbation and chemical shift perturbation data acquired on sample dilution is also presented. The general utility of the dimer structure determination procedure and the possible relevance of SeR13 dimer formation are discussed. PMID- 20589906 TI - Expression and light sensitivity of clock genes Per1 and Per2 and immediate-early gene c-fos within the retina of early postnatal Wistar rats. AB - Mammalian retina contains a circadian clock that is composed of components similar to those of the master circadian clock within the suprachiasmatic nuclei of the hypothalamus. The aim of the present study was to elucidate whether, when, and where the transcripts of the clock genes Per1 and Per2 and the immediate early gene c-fos are spontaneously expressed and/or induced by light in the newborn rat retina. At postnatal day 1 (P1), P3, P5, and P10, Wistar rat pups were released into constant darkness, and a 30-minute light pulse was administered during the subjective day or during the first or second part of subjective night. Gene expression was determined 30 minutes, 1 hour, 2 hours, and 4 hours after the light pulse by in situ hybridization followed by emulsion autoradiography. Endogenous expression of Per1 was detected in the neuroblastic retina, and Per2 expression was detected in the inner part of the neuroblastic retina from birth. Light pulses induced c-fos expression in ganglion cells from P1. Until P5, the cells were localized in the dorsal part of the retina, but, at P10, they were already distributed across the entire retinal circumference. Light pulses also induced the expression of c-fos and Per1 in the retinal pigment epithelium until P3, but not afterward. Expression of the Per2 gene was not photoresponsive until P10. These data demonstrate that the rat retina is light sensitive immediately after birth. During early postnatal development, the spatial distribution of spontaneous and light-induced gene expression within the retinal layers changes gradually. PMID- 20589907 TI - Calcium-binding protein immunoreactivity characterizes the auditory system of Gekko gecko. AB - Geckos use vocalizations for intraspecific communication, but little is known about the organization of their central auditory system. We therefore used antibodies against the calcium-binding proteins calretinin (CR), parvalbumin (PV), and calbindin-D28k (CB) to characterize the gecko auditory system. We also examined expression of both glutamic acid decarboxlase (GAD) and synaptic vesicle protein (SV2). Western blots showed that these antibodies are specific to gecko brain. All three calcium-binding proteins were expressed in the auditory nerve, and CR immunoreactivity labeled the first-order nuclei and delineated the terminal fields associated with the ascending projections from the first-order auditory nuclei. PV expression characterized the superior olivary nuclei, whereas GAD immunoreactivity characterized many neurons in the nucleus of the lateral lemniscus and some neurons in the torus semicircularis. In the auditory midbrain, the distribution of CR, PV, and CB characterized divisions within the central nucleus of the torus semicircularis. All three calcium-binding proteins were expressed in nucleus medialis of the thalamus. These expression patterns are similar to those described for other vertebrates. PMID- 20589909 TI - Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain. AB - Serotonin neurons play a major role in many normal and pathological brain functions. In the rat these neurons have a varying number of cotransmitters, including neuropeptides. Here we studied, with histochemical techniques, the relation between serotonin, some other small-molecule transmitters, and a number of neuropeptides in the dorsal raphe nucleus (DRN) and the adjacent ventral periaqueductal gray (vPAG) of mouse, an important question being to establish possible differences from rat. Even if similarly distributed, the serotonin neurons in mouse lacked the extensive coexpression of nitric oxide synthase and galanin seen in rat. Although partly overlapping in the vPAG, no evidence was obtained for the coexistence of serotonin with dopamine, substance P, cholecystokinin, enkephalin, somatostatin, neurotensin, dynorphin, thyrotropin releasing hormone, or corticotropin-releasing hormone. However, some serotonin neurons expressed the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD). Work in other laboratories suggests that, as in rat, serotonin neurons in the mouse midline DRN express the vesicular glutamate transporter 3, presumably releasing glutamate. Our study also shows that many of the neuropeptides studied (substance P, galanin, neurotensin, dynorphin, and corticotropin-releasing factor) are present in nerve terminal networks of varying densities close to the serotonin neurons, and therefore may directly or indirectly influence these cells. The apparently low numbers of coexisting messengers in mouse serotonin neurons, compared to rat, indicate considerable species differences with regard to the chemical neuronatomy of the DRN. Thus, extrapolation of DRN physiology, and possibly pathology, from rat to mouse, and even human, should be made with caution. PMID- 20589908 TI - Synaptic and nonsynaptic localization of protocadherin-gammaC5 in the rat brain. AB - It has been proposed that gamma-protocadherins (Pcdh-gammas) are involved in the establishment of specific patterns of neuronal connectivity. Contrary to the other Pcdh-gammas, which are expressed in the embryo, Pcdh-gammaC5 is expressed postnatally in the brain, coinciding with the peak of synaptogenesis. We have developed an antibody specific for Pcdh-gammaC5 to study the expression and localization of Pcdh-gammaC5 in brain. Pcdh-gammaC5 is highly expressed in the olfactory bulb, corpus striatum, dentate gyrus, CA1 region of the hippocampus, layers I and II of the cerebral cortex, and molecular layer of the cerebellum. Pcdh-gammaC5 is expressed in both neurons and astrocytes. In hippocampal neuronal cultures, and in the absence of astrocytes, a significant percentage of synapses, more GABAergic than glutamatergic, have associated Pcdh-gammaC5 clusters. Some GABAergic axons show Pcdh-gammaC5 in the majority of their synapses. Nevertheless, many Pcdh-gammaC5 clusters are not associated with synapses. In the brain, significant numbers of Pcdh-gammaC5 clusters are located at contact points between neurons and astrocytes. Electron microscopic immunocytochemistry of the rat brain shows that 1) Pcdh-gammaC5 is present in some GABAergic and glutamatergic synapses both pre- and postsynaptically; 2) Pcdh-gammaC5 is also extrasynaptically localized in membranes and in cytoplasmic organelles of neurons and astrocytes; and 3) Pcdh-gammaC5 is also localized in perisynaptic astrocyte processes. The results support the notions that 1) Pcdh-gammaC5 plays a role in synaptic specificity and/or synaptic maturation and 2) Pcdh-gammaC5 is involved in neuron-neuron synaptic interactions and in neuron-astrocyte interactions, including perisynaptic neuron-astrocyte interactions. PMID- 20589910 TI - Melatonin receptors in the brain of the European sea bass: An in situ hybridization and autoradiographic study. AB - Melatonin is synthesized in the pineal organ and retina of vertebrates and exhibits a clear nocturnal rhythm of secretion. This hormone influences a number of important physiological processes acting through specific transmembrane G protein-coupled receptors. Recently, we have cloned three different melatonin receptors in sea bass belonging to the MT1, MT2, and Mel1c subtypes. In this paper, we have analyzed the central expression of the MT1 gene by in situ hybridization and compared its distribution with the localization of 2-[(125)I] iodomelatonin binding sites. In situ hybridization and autoradiographic studies provided consistent results. Melatonin receptors were mainly expressed in visually related areas of the sea bass brain, such as the pretectal area, glomerular complex, optic tectum, torus longitudinalis, and thalamus. A conspicuous expression was also detected in neuroendocrine regions including the ventral telencephalon, preoptic area, and hypothalamus. Furthermore, melatonin receptors were evident in the ganglionic cell layer of the cerebellum. The presence of iodomelatonin binding and/or MT1 mRNA-expressing cells was also observed in the hindbrain, in particular in the oculomotor and trigeminal nuclei and in the reticular formation. Our results suggest an important role of MT1 in the mediation of melatonin actions in visual/light integration, mechanoreception, somatosensation, eye-body motor coordination, and integrative and neuroendocrine functions. Remarkable differences in the number and distribution of brain nuclei expressing MT1 mRNAs in sea bass and trout, the only fish species analyzed to date, represent another piece of evidence for differences in the organization of the visual and circadian systems observed between salmoniform and perciform teleosts. PMID- 20589911 TI - Similarities and differences in the forebrain expression of Lhx1 and Lhx5 between chicken and mouse: Insights for understanding telencephalic development and evolution. AB - We compared expression of the paralogous LIM-homeodomain genes Lhx1 and Lhx5 in the developing rostral forebrain of mouse and chicken. Both genes are expressed in similar patterns in the septum, preoptic region, and related areas of the basal telencephalon, including the medial septum/diagonal band nuclei and the medial extended amygdala. In the septum, the expression of Lhx5 and Lhx1 appears to be specifically related to the pallial septum and its derivatives in mouse and chicken, and may produce the glutamatergic neurons observed in the diagonal band/medial septum nuclei. The preoptic area expresses both Lhx1 and Lhx5 in mouse and chicken, and appears to produce gamma-aminobutyric acid (GABA)ergic, glutamatergic, and cholinergic cells for the preoptic region and basal telencephalon. In addition, in mouse and chicken Lhx5 is expressed in two extratelencephalic domains that appear to contribute Lhx5-expressing cells to the basal telencephalon, including the supraoptoparaventricular hypothalamic domain and the eminentia thalami. In contrast, there are striking differences in the pallial expression of Lhx1 and Lhx5 between mouse and chicken. Both genes are expressed in Cajal-Retzius cells, and Lhx5 is also present in most pallial sources of Cajal-Retzius cells (including the cortical hem and retrobulbar area) and in the olfactory bulbs in the mouse. In contrast, putative Cajal-Retzius cells, the retrobulbar area, and the olfactory bulb of chicken do not express the paralog genes cLhx1/cLhx5. Moreover, the cortical hem-although it expresses cLhx5 is very tiny in chicken. We discuss the consequences of these differences in Lhx1/Lhx5 expression between mouse and chicken for pallial/cortical evolution. PMID- 20589912 TI - Life-span phenotypes of elav and Rbp9 in Drosophila suggest functional cooperation of the two ELAV-family protein genes. AB - The ELAV family of RNA-binding proteins is involved in various aspects of the post-transcriptional regulation of gene expression, from alternative splicing to translation. The members of this family have been shown to interact with each other and have been suggested to function as homo- and/or hetero-multimers. However, the functional interactions among them have not been demonstrated in vivo. In this study, we examined the genetic interaction between elav and Rbp9, two of the three genes encoding ELAV-family proteins in Drosophila. Mutants of both elav and Rbp9 showed shorter life spans than the control, with elav showing a shorter life span than Rbp9. The survival curve of elav-Rbp9 double-mutant flies was indistinguishable from that of elav single-mutant flies, suggesting that both mutations affect longevity through the same pathway. Considering the fact that both genes are co-expressed in adult neurons, we hypothesize that ELAV and Rbp9 cooperate to maintain the functional integrity of the adult nervous system. PMID- 20589913 TI - Is there a role for routinely screening children with autism spectrum disorder for creatine deficiency syndrome? AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that presents in the first three years of life. Currently, diagnosis of ASD is based on its behavioural manifestations, as laboratory diagnostic tests do not exist. Creatine deficiency syndrome (CDS) is one form of inborn error of metabolism where affected individuals have similar clinical features to individuals with ASD. Abnormal urinary creatine (CR) and guanidinoacetate (GAA) levels have been reported as biomarkers of CDS. We hypothesized that screening for abnormal levels of urinary CR and GAA in children with ASD may assist in identifying a subgroup of ASD individuals who can be managed with dietary interventions. Morning urine samples were collected from children with and without autism and analyzed for CR and GAA levels. Results showed there was no statistically significant difference in urinary CR:creatinine and GAA:creatinine between the children with ASD and sibling or unrelated controls. In conclusion, routine screening for abnormal urinary CR and GAA could be considered in ASD diagnostic protocols; however, individuals positive for CDS are likely to be rare in an ASD cohort. PMID- 20589914 TI - Dietary methionine intake and neural tube defects in Mexican-American women. AB - BACKGROUND: Nutrients other than maternal folic acid are also thought to play a role in preventing neural tube defects (NTDs). Evidence suggests that methionine interacts with folic acid and vitamin B(12) in the methylation of contractile proteins involved in closing the neural folds. The role of dietary intake of methionine in NTD risk has not been specifically studied among Mexican Americans, a population with one of the highest prevalences of NTDs in the United States. METHODS: We conducted a case-control study of 184 Mexican American women with NTD affected pregnancies (case women) and 225 women with normal offspring (control women) who resided along the Texas-Mexico border. The average daily intakes of methionine were calculated from periconceptional food frequency questionnaire data. Women were categorized according to quartiles of daily methionine intake, based on the control mothers' distribution, and the risk for an NTD-affected pregnancy was calculated using the lowest quartile of intake as the referent. RESULTS: With adjustment for income, body mass index, hyperinsulinemia, and diarrhea, the odds ratios for increasing quartile of methionine intake were: 0.95 (95% confidence interval [CI], 0.48,1.90), 0.92 (95% CI, 0.46,1.84), and 0.66 (95% CI, 0.30,1.45). Some evidence of interaction between dietary methionine and serum vitamin B(12) was noted particularly at higher levels of both components. CONCLUSIONS: This study was limited by a small sample size but examined this association in an exclusively Hispanic population. Results were suggestive of a potential protective effect for NTDs with increasing maternal dietary methionine intake. PMID- 20589915 TI - Secular trends of hypospadias prevalence and factors associated with it in southeast China during 1993-2005. AB - BACKGROUND: The aim of this study is to describe the prevalence of hypospadias and its time trends during 1993-2005 in southeast China, and to explore the potential risk factors. METHODS: The study population included all male live and still births (at least 20 weeks of gestation) in 11 cities and counties in Jiangsu and Zhejiang Provinces in Southeast China born during January 1, 1993, through December 31, 2005. RESULTS: Overall prevalence of hypospadias was 5.8 per 10,000 male births and presented an increasing trend during 1993-2005 (with chi(for trend) (2) of 3.94, p = 0.047). Prevalence of coronal hypospadias and those with unknown sites increased from 1.7 and 0.3 per 10,000 male births in 1993 to 3.6 and 1.4 per 10,000 male births in 2005, respectively (with chi(for trend) (2) of 7.29 and 9.05, p = 0.007 and p = 0.002, respectively), but prevalence of perineal hypospadias decreased (with chi(for trend) (2) of 7.13, p = 0.008). Maternal fever during first trimester, birth of twins or more children, and year of birth were independent risk factors for hypospadias, with odds ratios of 4.14 (95% CI, 1.32-12.83), 3.37 (95% CI, 1.73-6.58), and 1.04 (95% CI, 1.00 1.08), respectively, after adjusting for confounding factors with multivariable logistic regression analysis. CONCLUSIONS: Prevalence of hypospadias increased during 1993-2005 in the two provinces in southeast China. Maternal fever in the first trimester and birth of twins or more children are associated with the risk for hypospadias. PMID- 20589916 TI - International trends of Down syndrome 1993-2004: Births in relation to maternal age and terminations of pregnancies. AB - BACKGROUND: The aim of this study was to examine trends of Down syndrome (DS) in relation to maternal age and termination of pregnancies (ToP) in 20 registries of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). METHODS: Trends of births with DS (live-born and stillborn), ToP with DS, and maternal age (percentage of mothers older than 35 years) were examined by year over a 12-year period (1993-2004). The total mean number of births covered was 1550,000 annually. RESULTS: The mean percentage of mothers older than 35 years of age increased from 10.9% in 1993 to 18.8% in 2004. However, a variation among the different registers from 4-8% to 20-25% of mothers >35 years of age was found. The total mean prevalence of DS (still births, live births, and ToP) increased from 13.1 to 18.2/10,000 births between 1993 and 2004. The total mean prevalence of DS births remained stable at 8.3/10,000 births, balanced by a great increase of ToP. In the registers from France, Italy, and the Czech Republic, a decrease of DS births and a great increase of ToP was observed. The number of DS births remained high or even increased in Canada Alberta, and Norway during the study period. CONCLUSIONS: Although an increase in older mothers was observed in most registers, the prevalence of DS births remained stable in most registers as a result of increasing use of prenatal diagnostic procedures and ToP with DS. PMID- 20589917 TI - Rudimentary claws and pigmented nail-like structures on the distal tips of the digits of Wnt7a mutant mice: Wnt7A suppresses nail-like structure development in mice. AB - BACKGROUND: As Wnt7a mutant mice exhibit double ventral structures in the digits of autopods, it has been accepted that dorsal-ventral identity in limb development is regulated by the Wnt7a signal. The most important evidence for this was the presence of surface pads, typical characteristics of ventral structures, on the dorsal side of digital tips and at the base of digits and their pigmentation. METHODS: The morphologic features of the appendages on the distal tips of digits were inspected in the fore- and hindlimbs of mice having a different Wnt7a mutation. The digital structures were examined macroscopically and histologically. RESULTS: The Wnt7a homozygous mutant mice with defects in postaxial digits had rudimentary claws or claws and pigmented nail-like structures, instead of dorsal pads, on the distal digital tips and hairs on the dorsal surface of the digits of fore- and hindlimbs. Furthermore, pigmented ectopic nail-like structures but not pads were also present on the dorsal surface of the base of digits. Double ventral structures were observed in the bones and tendons, excluding pads in digital areas. CONCLUSIONS: These findings suggest that Wnt7a is not necessarily an exclusive dorsalizing signal to the dorsal ectoderm of the digital areas of autopods. Rather, the Wnt7a signal may participate in suppression of the development of pigmented nail-like structures in normal limb development. This means that even rodents, a species lower than primates in the evolution from claws to nails, have molecular potential to develop cutaneous appendages similar to nails at their location. PMID- 20589918 TI - Septo-optic dysplasia and associations with amyoplasia and gastroschisis. AB - BACKGROUND: The causes of septo-optic dysplasia, amyoplasia, and gastroschisis are mostly unknown. CASES: We present a patient with septo-optic dysplasia and amyoplasia. We also present a patient with features of septo-optic dysplasia, gray matter heterotopias, and gastroschisis. CONCLUSIONS: These previously unreported combinations provide further support for vascular disruption in embryonic or fetal life as an etiological factor in these conditions. PMID- 20589919 TI - Protracted, dose-dependent weight loss after addition of ziprasidone to a stable regimen of clozapine. PMID- 20589920 TI - Effect of nicotine on saccadic eye movement latencies in non-smokers. AB - OBJECTIVE: Recently, saccadic eye movement tasks have been used to assess the effects of nicotine on higher cognitive processes, including inhibitory control. Saccadic task switching methods suggest that there is prolonged inhibition of the saccadic eye movement system following antisaccade trials. The objective of this research was to examine effects of nicotine on inhibition using saccadic task switching paradigms. METHODS: Nicotine and placebo lozenges were administered on separate days to 40 non-smokers who performed prosaccade and antisaccade tasks. In addition, participants performed a series of trials in which prosaccade and antisaccade tasks were switched. Eye movement latencies were recorded. RESULTS: Participants responded significantly faster for the nicotine condition than for the placebo condition. A switch benefit was observed for only placebo antisaccade trials, in that latencies of repetition trials were significantly longer than those of switch trials. In addition, an analysis of the repetition trials showed an interaction between saccade type and sequence position for the placebo condition, but not the nicotine condition. CONCLUSION: Inhibition persists after antisaccade trials in a switching paradigm, but that the duration of this inhibition is reduced by nicotine. PMID- 20589921 TI - The loudness dependence auditory evoked potential is insensitive to acute changes in serotonergic and noradrenergic neurotransmission. AB - BACKGROUND: The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as an electrophysiological marker for assessing serotonergic function in vivo in humans, although accumulating evidence suggests that it is insensitive to acute changes in serotonergic neurotransmission. Very little is known about the sensitivity of the LDAEP to other neurotransmitter systems including the noradrenergic system. The current study examined the effects of noradrenergic modulation as well as serotonergic modulation on the LDAEP. METHODS: The study utilised a double-blind placebo-controlled design in which the LDAEP in 17 healthy males and females was tested following acute administration of each of citalopram (20 mg), reboxetine (4 mg) and placebo. RESULTS: Neither citalopram nor reboxetine modulated the LDAEP relative to placebo treatment (p > 0.05). CONCLUSION: These findings suggest that the LDAEP is insensitive to acute changes in serotonergic or noradrenergic neurotransmission and thus is a poor pharmacodynamic marker of these systems. PMID- 20589922 TI - Single-dose pharmacokinetics of paliperidone extended-release tablets in healthy Chinese subjects. AB - OBJECTIVE: Paliperidone is the active metabolite of risperidone. This single center, double-blind, randomized, single-dose study characterized the pharmacokinetics of 3 mg and 9 mg of paliperidone ER OROS in healthy Chinese subjects. METHODS: 24 subjects (13 male, 11 female), aged 19-35 years, with a BMI of 19.0-24.6 kg/m(2) participated. Blood samples were collected immediately before and over 96 h following single oral doses of 3 mg and 9 mg paliperidone. Plasma paliperidone concentrations were determined, and pharmacokinetic parameters were analyzed. RESULTS: Paliperidone's disposition after oral administration was characterized by a one-compartment pharmacokinetic model. Paliperidone was well absorbed (median t(max): 24 h after a 3-mg dose, and 26 h after a 9-mg dose). Apparent clearance and apparent volume of distribution were not significantly different between the two doses. C(max), AUC(0-t), and AUC(0 infinity) were dose-dependent. Pharmacokinetics was linear with respect to time; Geometric mean t(1/2) was 22.8 h and 21.4 h in 3-mg and 9-mg groups, respectively. No clinically significant safety issues were identified. CONCLUSIONS: The pharmacokinetic results obtained in Chinese subjects were similar to those obtained in Japanese and Caucasian subjects. PMID- 20589923 TI - Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia. AB - OBJECTIVE: This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in schizophrenia. METHODS: We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of the MAOB gene. RESULTS: There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. CONCLUSIONS: These data do not suggest that the MAOA gene VNTR and MAOB gene A644G polymorphisms are associated with antipsychotic-induced RLS symptoms in schizophrenia. However, we found that the haplotype frequencies differed between the male schizophrenic patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with schizophrenia. PMID- 20589924 TI - Caffeine and stress alter salivary alpha-amylase activity in young men. AB - OBJECTIVE: We examined the effects of caffeine and a psychological stressor on salivary alpha-amylase (sAA) in healthy young males (age 18-30 years) who consumed caffeine on a daily basis. METHODS: Using a between-subjects, double blind, placebo-controlled design, 45 participants received either 200 or 400 mg of caffeine (Vivarin) or placebo, rested for 20 min, and then performed 20 min of mental arithmetic. Saliva samples (assayed for sAA and caffeine), blood pressure, and heart rate were taken before (baseline) and 15 min after the math stressor (stress). RESULTS: Baseline sAA activity did not differ among the treatment groups; however, there was a statistically significant time by caffeine group interaction. Changes in sAA activity across the session were dependent on the amount of caffeine consumed. Following the challenge period, sAA activity among the placebo group was the lowest and sAA activity among the 400 mg treatment group was the highest. Separate repeated-measures ANOVAs conducted for each drug treatment group revealed that sAA activity increased in response to stress and caffeine (i.e., 200 and 400 mg groups) but not to stress alone (i.e., placebo group). CONCLUSIONS: Findings provide evidence for acute sAA changes in response to caffeine and stress in habitual caffeine users. PMID- 20589925 TI - Differential effects of the aromas of Salvia species on memory and mood. AB - This study investigated the potential for the aromas of the essential oils of Salvia species to affect cognition and mood in healthy adults. Research has demonstrated that orally administered Salvia officinalis and Salvia lavandulaefolia are capable of modulating cognition and mood. The active compounds in the herbal products might also be present in the aromas and so produce similar effects. In an independent groups design, three conditions, S. officinalis aroma, S. lavandulaefolia aroma and no aroma were employed. One hundred and thirty-five healthy volunteers acted as participants, with 45 in each condition. Cognitive performance was assessed via the Cognitive Drug Research (CDR) System. Bond-Lader mood scales measured the participants' mood on three dimensions before and after the cognitive tasks. Data analysis revealed that the S. officinalis aroma group performed significantly better than the control group on the quality of memory and secondary memory primary outcome factors from the test battery. The Alert mood measure displayed significant differences between both aromas and the control condition. These findings suggest that the aromas of essential oils of Salvia species reproduce some but not all of the effects found following oral herb administration, and that interesting dissociations occur between subjective and objective responses. PMID- 20589926 TI - Behavioral arousal in response to stress and drug cue in alcohol and cocaine addicted individuals versus healthy controls. AB - Negative emotional arousal in response to stress and drug cues is known to play a role in the development and continuation of substance use disorders. However, studies have not examined behavioral indicators of such arousal. OBJECTIVE: The current study examined behavioral and bodily arousal in response to stress and drug cue in individuals with alcohol dependence and cocaine dependence as compared to healthy controls using a new scale. METHODS: Fifty-two alcohol dependent (AD group), 45 cocaine dependent (COC group), and 68 healthy controls (HC group) were exposed to individually developed stressful, drug-cue, and neutral-relaxing imagery. Behavioral and bodily responses were assessed with a new scale, the Behavioral Arousal Scale (BAS). RESULTS: The BAS showed acceptable inter-rater reliability and internal consistency and correlated with subjective negative emotion and craving. BAS scores were higher in stress than neutral conditions for all three groups. COC participants showed higher BAS response to stress than AD or HC participants. COC and AD participants showed greater BAS response to drug cue than HC participants. CONCLUSION: Behavioral arousal is a domain in which stress and drug related arousal is expressed and assessment of this domain could provide unique information about vulnerability to craving and relapse in addicted populations. PMID- 20589927 TI - Verbal memory improved by D-amphetamine: influence of the testing effect. AB - OBJECTIVE: The improvement of long-term retention of verbal memory after an acute administration of D-amphetamine in recall and recognition tasks has been ascribed to an influence of the drug on memory consolidation. Because recent research has demonstrated that intermediate testing is of overriding importance for retention, we investigated whether D-amphetamine modulates the repeated testing effect in verbal long-term recognition. METHOD: Forty men participated in two double blind placebo controlled studies. In Experiment 1, we manipulated the number of recognition tests and in Experiment 2, we compared repeated with nonrepeated testing of the same items. RESULTS: Drug effects were observed on delayed tests only, leaving immediate recognition unaffected. Number of intermediate recognition tests and repeated testing of the same items were not affected by D amphetamine. CONCLUSIONS: We conclude that the D-amphetamine memory enhancement is not related to the testing effect. This result supports that D-amphetamine modulates other aspects of the consolidation process, probably related to context effects. PMID- 20589928 TI - Behavior abnormality following intravenous immunoglobulin treatment in patients with primary antibody deficiencies. AB - OBJECTIVE: Treatment with intravenous immunoglobulin (IVIG) is considered a safe therapy for patients with primary antibody deficiencies (PADs), whilst adverse effects have been frequently reported. Meantime behavioral disorders reactions have not been reported yet. In this study, we describe for the first time a group of patients with PADs, who were under IVIG therapy and experienced some behavioral disorders. METHODS: Five patients, including two hyper IgM syndromes, one X-linked agammaglobulinemia, one common variable immunodeficiency, and one hypo IgM disease, were surveyed. Analysis of Conner's Parents Rating Scales Revised Short (CPRS-R:S) and child behavior checklist (CBCL) was performed for the patients, suspected to hyperactivity. RESULTS: Analysis of CPRS-R:S showed an evidence of mild hyperactivity before IVIG administration in four patients, whereas another patient had evidence of severe hyperactivity. After IVIG administration, hyperactivity scores of three patients were changed from mild hyperactive behavior to markedly hyperactive behavior or attention deficit hyperactivity disorder range of hyperactivity. In the CBCL scores, there were abnormal externalization scores for three patients; while two remaining patients had abnormal internalization scores. CONCLUSIONS: Although predisposition to behavioral disorders can be due to a genetic background, further investigations are necessary to test the hypotheses about responsibility of either IVIG or underling disease in progression of behavioral abnormalities. PMID- 20589929 TI - Biochemical T2* MR quantification of ankle arthrosis in pes cavovarus. AB - Pes cavovarus affects the ankle biomechanics and may lead to ankle arthrosis. Quantitative T2 STAR (T2*) magnetic resonance (MR) mapping allows high resolution of thin cartilage layers and quantitative grading of cartilage degeneration. Detection of ankle arthrosis using T2* mapping in cavovarus feet was evaluated. Eleven cavovarus patients with symptomatic ankle arthrosis (13 feet, mean age 55.6 years, group 1), 10 cavovarus patients with no or asymptomatic, mild ankle arthrosis (12 feet, mean age 41.8 years, group 2), and 11 controls without foot deformity (18 feet, mean age 29.8 years, group 3) had quantitative T2* MR mapping. Additional assessment included plain radiographs and the American Orthopaedic Foot and Ankle Society (AOFAS) score (groups 1 and 2 only). Mean global T2* relaxation time was significantly different between groups 1 and 2 (p = 0.001) and groups 1 and 3 (p = 0.017), but there was no significance for decreased global T2* values in group 2 compared to group 3 (p = 0.345). Compared to the medial compartment T2* values of the lateral compartment were significantly (p = 0.025) higher within group 1. T2* values in the medial ankle joint compartment of group 2 were significantly lower than those of group 1 (p = 0.019). Ankle arthrosis on plain radiographs and the AOFAS score correlated significantly with T2* values in the medial compartment of group 1 (p = 0.04 and 0.039, respectively). Biochemical, quantitative T2* MR mapping is likely effective to evaluate ankle arthrosis in cavovarus feet but further studies are required. PMID- 20589930 TI - Thermal analysis reveals differential effects of various crosslinkers on bovine annulus fibrosis. AB - Treatment of a pathological spinal disc in vivo by injection of protein crosslinking reagents to restore the disc's mechanical properties is a new approach to the treatment of degenerative disc disease. In this study, the thermal stability of the collagen in disc annulus was measured by differential scanning calorimetry following treatment with six different crosslinking agents. The crosslinkers used were; L-threose (LT), genipin (GP), methylglyoxal (MG), 1 ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), glutaraldehyde (GA), and proanthrocyanidin (PA). Untreated tissue displayed a prominent peak at about 66-68 degrees C. Comparison of endothermal patterns of untreated and crosslinker-treated disc annulus tissue samples showed that a new peak appeared at a higher temperature following treatment. The temperature of the new peak qualitatively depended on the crosslinker in the following order GA > MG > GP > PA = EDC > LT, suggesting that the enhanced thermal stability of collagen in the annulus tissue was related to the nature of the crosslinker. Also, the enthalpic ratios of the lower temperature (noncrosslinked) peaks in the treated and untreated tissue, and of the higher and lower temperature peaks in the treated tissue, both indicated that the various agents crosslinked the tissue with different efficiencies. Our data suggest that the ability of GP to penetrate into the disc and form long- and short-range crosslinks may make it the most suitable candidate for clinical development. In addition, binary combinations of long- and short-range crosslinkers, such as PA with LT, may also provide synergistic effects due to their substantially different physicochemical properties. PMID- 20589931 TI - Regulation of apoptosis in nucleus pulposus cells by optimized exogenous Bcl-2 overexpression. AB - Although the etiology of intervertebral disc degeneration is poorly understood, one possible approach to regulate the process of intervertebral disc degeneration may include the inhibition of apoptosis. We investigated the anti-apoptotic effects of bcl-2 in nucleus pulposus cells to enhance disc cell survival. Rat nucleus pulposus cells were transfected in vitro with a codon optimized rat bcl-2 gene. Forty-eight hours after transfection, cells were cultured in serum-deprived medium. After serum withdrawal, the cells were evaluated for bcl-2 protein levels and cell apoptosis. To investigate the effects of bcl-2 overexpression on the final apoptotic pathways and on basic genes important for nucleus pulposus homeostasis, mRNA levels of caspase-3, type II collagen, and aggrecan were also quantified. Nucleus pulposus cells were successfully transfected with codon optimized bcl-2 gene, which effectively reduced serum starvation-induced cell apoptosis. Overexpression of bcl-2 also reduced the mRNA expression level of caspase-3. mRNA levels of type II collagen and aggrecan were significantly higher in bcl-2 transfected groups compared to control plasmid vector groups after serum withdrawal. We firstly showed that bcl-2 overexpression in intervertebral disc cells was effective in preventing in vitro apoptotic cell death, indicating the potential advantages of this therapeutic approach in regulating disc degeneration. PMID- 20589932 TI - Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: poor prognosis and prenatal origin. AB - The ETV6/ABL1 (TEL/ABL) fusion gene is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1-positive hematological malignancy have been published, diagnosed with chronic myeloid leukemia, other types of chronic myeloproliferative neoplasm, acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This study reports three new cases (aged 8 months, 5 years, and 33 years) of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed ALL patients (335 children and 57 adults). A thorough review of the literature and an analysis of all published data, including the three new cases, suggest poor prognosis of ETV6/ABL1-positive acute leukemias. The course of the disease in the two pediatric patients is characterized by minimal residual disease monitoring, using quantification of both the ETV6/ABL1 transcript and immunoreceptor gene rearrangements. Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1-positive disease. Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally. PMID- 20589933 TI - Factors associated with low screening for breast cancer in the Palestinian Authority: relations of availability, environmental barriers, and cancer-related fatalism. AB - BACKGROUND: The current study was conducted to assess screening behaviors in relation to cultural and environmental barriers among Palestinian women in the West Bank. METHODS: The participants were 397 women, ages 30 to 65 years, residing in the Palestinian Authority, and a stratified sample method was used (98.3% participation rate). The participants completed questionnaires on breast examination behaviors and knowledge, on perceived cancer fatalism and health beliefs, and on environmental barriers scales. RESULTS: Greater than 70% of the women had never undergone mammography or clinical breast examination (CBE), whereas 62% performed self breast examination (SBE). Women were more likely to undergo mammography if they were less religious (odds ratio [OR], 0.59; 95% confidence interval [95% CI], 0.47-0.81) and if they expressed lower personal barriers (OR, 0.59; 95% CI, 0.29-0.76) and lower fatalism (OR, 0.39; 95% CI, 0.28 0.63). A higher likelihood for CBE was related to being Christian (OR, 2.91; 95% CI, 1.49-5.73) and being less religious (OR, 0.32; 95% CI, 0.13-0.78), to perceived higher effectiveness of CBE (OR, 1.46; 95% CI, 1.20-1.79), and to perceived lower cancer fatalism (OR, 0.35; 95% CI, 0.28-0.60). Women were more likely to perform SBE if they were more educated, resided in cities, were Christian, were less religious, had a first-degree relative with breast cancer, perceived higher effectiveness and benefits of SBE, and perceived lower barriers and fatalism. CONCLUSIONS: Participants reported a combination of personal, cultural, and environmental barriers, which should be addressed by educational programs and followed by the allocation of resources for early detection and treatment of breast cancer. PMID- 20589934 TI - Clonal heterogeneity in childhood myelodysplastic syndromes--challenge for the detection of chromosomal imbalances by array-CGH. AB - To evaluate whether copy number alterations (CNAs) are present that may contribute to disease development and/or progression of childhood myelodysplastic syndromes (MDS), 36 pediatric MDS patients were analyzed using array-based comparative genome hybridization (aCGH). In addition to monosomy 7, the most frequent chromosome aberration in childhood MDS, novel recurrent CNAs were detected. They included a loss of 3p14.3-p12.3, which contains the putative tumor suppressor gene FHIT, a loss of 7p21.3-p15.3, a loss of 9q33.3-q34.3 (D184) and microdeletions in 17p11.2, 6q23 containing MYB, and 17p13 containing TP53. In this small patient cohort, patients without CNA, patients with monosomy 7 only and patients with one CNA in addition to monosomy 7 did not differ in their survival. As expected, all patients with complex karyotypes, including two patients with deletions of TP53, died. A challenge inherent to aCGH analysis of MDS is the low percentage of tumor cells. We evaluated several approaches to overcome this limitation. Genomic profiles from isolated granulocytes were of higher quality than those from bone marrow mononuclear cells. Decreased breakpoint calling stringency increased recognition of CNAs present in small clonal populations. However, further analysis using a custom-designed array showed that these CNAs often did not confirm the findings from 244k arrays. In contrast, constitutional CNVs were reliably detected on both arrays. Moreover, aCGH on amplified DNA from distinct myeloid clusters is a new approach to determine CNAs in small subpopulations. Our results clearly emphasize the need to verify array-CGH results by independent methods like FISH or quantitative PCR. PMID- 20589935 TI - Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. AB - To investigate the molecular mechanism of mammary carcinogenesis and identify novel molecular targets for breast cancer therapy, we analyzed genome-wide gene expression profiles of 81 clinical breast cancer samples. Here, we report the critical role of LGN/GPSM2 (Leu-Gly-Asn repeat-enriched protein/G-protein signaling modulator 2) in the growth of breast cancer cells. Semiquantitative RT PCR and Northern blot analyses confirmed upregulation of LGN/GPSM2 in a large proportion of breast cancers. Immunocytochemical staining identified LGN/GPSM2 at the spindle in cells at metaphase, and at midzone and midbody in cytokinetic cells. Western blot analysis indicated the highest expression and the phosphorylated form of LGN/GPSM2 protein in G2/M phase. Treatment with small interfering RNAs (siRNAs) targeting LGN/GPSM2 caused incompletion of cell division and resulted in significant growth suppression of breast cancer cells. We found that the 450th threonine (Thr450) of LGN/GPSM2 was phosphorylated by the serine/threonine kinase PBK/TOPK during mitosis. Overexpression of LGN/GPSM2 T450A in which Thr450 was substituted with alanine induced growth suppression and aberrant chromosomal segregation. These findings imply an important role of LGN/GPSM2 in cell division of breast cancer cells and suggest that the PBK/TOPK LGN/GPSM2 pathway might be a promising molecular target for treatment of breast cancer. PMID- 20589936 TI - Chromosome band 17q21 in breast cancer: significant association between beclin 1 loss and HER2/NEU amplification. AB - Treatment success of breast cancer patients with trastuzumab alone or in combination depends not only on HER2/NEU amplification but also on PTEN and PI3K status and efficient cell death programs. In this pilot study, we found a significant association between loss of beclin 1 and HER2/NEU amplification (both on 17q21) in breast cancers. This finding was confirmed in two public copy number microarray datasets. Furthermore, there is a trend associating beclin 1 loss with TP53 mutations, PI3KCA gene gain, and PTEN mutations. Finally, the observation that beclin 1 gene loss predicted a response to trastuzumab alone or in combination with other drugs is worthy of further confirmation in larger cohorts. Our results suggest that, beclin 1 loss may contribute to genome instability and to a defective autophagy that may lead to tumoral cell death in presence of competent apoptosis or senescence pathways. PMID- 20589937 TI - Role of mechanical loading in healing of massive bone autografts. AB - We assessed healing of a 3.5 cm autograft transport segment, denuded of periosteum, and docked to the healthy distal femur with an intramedullary nail. We hypothesized that healing relates to proximity to the healthy distal femur and to mechanical loading patterns. Total bone area, area of new bone apposition, and quality of new bone formed in the 2 weeks after surgery, and area and degree of perfusion 16 weeks after surgery were measured as a function of proximity and loading patterns (as defined by the major and minor centroidal axes, CA). At 16 weeks, no significant differences in early bone apposition or perfusion were observed as a function of distance from the healthy distal femur. Qualitatively, bone was well perfused, both vascularly and pericellularly, and highly remodeled. When cross-sections were pooled from distal to proximal through the docking zone and normalized for total bone area, significant differences in the amount of early proliferative woven bone were related to loading patterns. In contrast, no differences in normalized perfusion area were attributable to loading patterns. Furthermore, early bone apposition and perfusion decreased with increasing radial distance from the bone surface toward the intramedullary nail. Finally, no differences were observed in areas of resorption within the docking zone compared to baseline levels measured in the control (in bone removed to create the defect zone at the time of surgery). Interestingly, infilling of resorption spaces within docking zone specimens related significantly to predominant loading patterns, where areas within the major CA exhibited significantly more infilling. PMID- 20589938 TI - Louis Pasteur, language, and molecular chirality. I. Background and dissymmetry. AB - Louis Pasteur resolved sodium ammonium (+/-)-tartrate in 1848, thereby discovering molecular chirality. Although hindered by the primitive state of organic chemistry, he introduced new terminology and nomenclature for his new science of molecular and crystal chirality. He was well prepared for this task by his rigorous education and innate abilities, and his linguistic achievements eventually earned him membership in the supreme institution for the French language, the Academie francaise. Dissymmetry had been in use in French from the early 1820s for disruption or absence of symmetry or for dissimilarity or difference in appearance between two objects, and Pasteur initially used it in the latter connotation, without any reference to handedness or enantiomorphism. Soon, however, he adopted it in the meaning of chirality. Asymmetry had been in use in French since 1691 but Pasteur ignored it in favor of dissymmetry. The two terms are not synonymous but it is not clear whether Pasteur recognized this difference in choosing the former over the latter. However, much of the literature mistranslates his dissymmetry as asymmetry. Twenty years before Pasteur the British polymath John Herschel proposed that optical rotation in the noncrystalline state is due to the "unsymmetrical" [his term] nature of the molecules and later used dissymmetrical for handed. Chirality, coined by Lord Kelvin in 1894 and introduced into chemistry by Mislow in 1962, has nearly completely replaced dissymmetry in the meaning of handedness, but the use of dissymmetry continues today in other contexts for lack of symmetry, reduction of symmetry, or dissimilarity. PMID- 20589939 TI - The effect of pulmonary hypertension on left ventricular diastolic function in chronic obstructive lung disease: a tissue Doppler imaging and right cardiac catheterization study. AB - BACKGROUND: Pulmonary hypertension (PH) caused by chronic obstructive lung disease (COLD) essentially involves the right heart. Also left ventricular (LV) systolic and diastolic functions may be affected. OBJECTIVES: The aim of this study was to investigate the effect of on LV diastolic function in patients with COLD. METHODS: A total of 47 patients with COLD and 20 controls were included in this study. All patients underwent Doppler echocardiography, tissue Doppler imaging examinations and right cardiac catheterization. The patients were divided into 2 subgroups according to mean pulmonary arterial pressure (mPAP): patients without PH (group1, n = 25) and with PH (group 2, n = 22). The following measurements were taken: peak velocity of early diastolic filling (E), peak late filling with atrial contraction (A), E/A ratio, deceleration time (DT) of E, isovolumic relaxation time (IVRT), early (Em) and late (Am) diastolic mitral lateral annulus velocity. RESULTS: Mitral E/A < 1 and Em < 8 cm/sec were higher in group 2 than in group 1 and the control group. There were significant correlations between mPAP and both mitral E/A (r:- 0.60) and Em (r:- 0.45). In multivariate model, mPAP was not found to be significant on mitral E/A ratio < 1, but there was a significant effect on mitral Em < 8 cm/sec (odds ratio [OR]:1.14, P < 0.05). CONCLUSION: This study shows that LV diastolic dysfunction in COLD is closely correlated to PH levels. Although increased mPAP may affect the mitral E/A ratio, it seems to have no effect on mitral E/A < 1, whereas it has an independent effect on Em < 8 cm/sec. PMID- 20589942 TI - Mobile aortic valve vegetation in a patient with infective endocarditis due to Enterococcus: ECG-gated 64-slice MDCT findings. PMID- 20589941 TI - Network analysis of resting state EEG in the developing young brain: structure comes with maturation. AB - During childhood, brain structure and function changes substantially. Recently, graph theory has been introduced to model connectivity in the brain. Small-world networks, such as the brain, combine optimal properties of both ordered and random networks, i.e., high clustering and short path lengths. We used graph theoretical concepts to examine changes in functional brain networks during normal development in young children. Resting-state eyes-closed electroencephalography (EEG) was recorded (14 channels) from 227 children twice at 5 and 7 years of age. Synchronization likelihood (SL) was calculated in three different frequency bands and between each pair of electrodes to obtain SL weighted graphs. Mean normalized clustering index, average path length and weight dispersion were calculated to characterize network organization. Repeated measures analysis of variance tested for time and gender effects. For all frequency bands mean SL decreased from 5 to 7 years. Clustering coefficient increased in the alpha band. Path length increased in all frequency bands. Mean normalized weight dispersion decreased in beta band. Girls showed higher synchronization for all frequency bands and a higher mean clustering in alpha and beta bands. The overall decrease in functional connectivity (SL) might reflect pruning of unused synapses and preservation of strong connections resulting in more cost-effective networks. Accordingly, we found increases in average clustering and path length and decreased weight dispersion indicating that normal brain maturation is characterized by a shift from random to more organized small world functional networks. This developmental process is influenced by gender differences early in development. PMID- 20589945 TI - Crystal quality and physical reactivity in the case of flufenamic acid (FFA). AB - In reality, no crystal is perfect. Crystals bear defects both in the bulk and on the surface. The purpose of this project is to study the correlation between crystal defect density and reactivity of physical transformation. The hypothesis is that larger crystals have the opportunity to pick up more defects during crystal growth than smaller crystals, therefore, have higher reactivity. Flufenamic acid (FFA) was used as a model compound. Phase transformation of crystal Form I (white) to Form III (yellow) of FFA was studied, and observed that larger crystals of FFA Form I transform faster. Furthermore, the etching pits identified on the major crystal faces (1 0 0) using atomic form microscopy (AFM) also showed that larger crystals had higher surface defect density than smaller ones, which correlates with the finding that larger crystals transforms faster than smaller ones. PMID- 20589943 TI - Gender differences in clinical features and in-hospital outcomes in ST-segment elevation acute myocardial infarction: from the Korean Acute Myocardial Infarction Registry (KAMIR) study. AB - BACKGROUND: Studies have suggested that women are biologically different and that female gender itself is independently associated with poor clinical outcome after an acute myocardial infarction (AMI). HYPOTHESIS: We analyzed data from the Korean Acute Myocardial Infarction Registry (KAMIR) to assess gender differences in in-hospital outcomes post ST-segment elevation myocardial infarction (STEMI). METHODS: Between November 2005 and July 2007, 4037 patients who were admitted with STEMI to 41 facilities were registered into the KAMIR database; patients admitted within 72 hours of symptom onset were selected and included in this study. RESULTS: The proportion of patients who had reperfusion therapy within 12 hours from chest pain onset was lower in women. Women had higher rates of in hospital mortality (8.6% vs 3.2%, P < .01), noncardiac death (1.5% vs 0.4%, P < .01), cardiac death (7.1% vs 2.8%, P < .01), and stroke (1.2% vs 0.5%, P < .05) than men. Multivariate logistic regression analysis identified age, previous angina, hypertension, a Killip class > or = II, a left ventricular ejection fraction (LVEF) < 40%, and a thrombolysis in myocardial infarction flow (TIMI) grade < or = 3 after angioplasty as independent risk factors for in-hospital death for all patients; however, female gender itself was not an independent risk factor. CONCLUSIONS: The results of this study show that although women have a higher in-hospital mortality than men, female gender itself is not an independent risk factor for in-hospital mortality. PMID- 20589946 TI - Accelerating proof of concept for small molecule drugs using solid-state chemistry. AB - In this perspective we have shown that the process of "proof of concept" (POC) in the early part of drug development can be greatly accelerated by close attention to the underlying solid-state chemistry (SSC) of a new chemical entity. POC seeks data that provide confidence in the therapeutic activity and safety of a new chemical entity, which can rapidly lead to a key "GO/NO-GO" decision point for further development. Due to the high cost of the development of new chemical entities and the current low overall productivity of obtaining successful candidates, the pharmaceutical industry is being required to develop accelerated POC strategies. The success of accelerated approaches to POC depends on a full understanding of the SSC of drugs in relation to solubility and stability. Dissolution-limited absorption due to poor solubility of drug substances is particularly important because it can lead to low exposure in animals and undesired bioavailability in humans. Choosing a desirable solid form with sufficient solubility and acceptable stability is essential in developing formulations for POC with superior quality. In this perspective we present an approach that utilizes SSC as part of a novel 2-year development strategy for reaching the pivotal clinical trial stage of development. PMID- 20589944 TI - Structural investigation of bacterial lipopolysaccharides by mass spectrometry and tandem mass spectrometry. AB - Mass spectrometric studies are now playing a leading role in the elucidation of lipopolysaccharide (LPS) structures through the characterization of antigenic polysaccharides, core oligosaccharides and lipid A components including LPS genetic modifications. The conventional MS and MS/MS analyses together with CID fragmentation provide additional structural information complementary to the previous analytical experiments, and thus contribute to an integrated strategy for the simultaneous characterization and correct sequencing of the carbohydrate moiety. PMID- 20589947 TI - Stabilization of metastable flufenamic acid by inclusion of mefenamic acid: solid solution or epilayer? AB - The physical stability of metastable form I of flufenamic acid (FFA) increased by using mefenamic acid (MFA) as an inclusion compound. We studied the extent of this effect and explained the mechanism by investigating the effect of the presence of MFA on nucleation and crystal growth of the mixed crystals and the effects it has on the surface morphology. We conclude that the polymorphic transformation of FFA was inhibited in the presence of MFA both by lowering the difference in free energy of the MFA/FFA I and MFA/FFA III solid solution crystals, and also by forming an epilayer, thus affecting the kinetics of the polymorphic transformation. PMID- 20589948 TI - Skin laser treatments enhancing transdermal delivery of ALA. AB - Drug delivery across skin has been limited due to barrier properties of the skin, especially those of the stratum corneum (SC). Use of the laser radiation has been suggested for the controlled removal of the SC. The purpose of this study was to study in vitro the influence of infrared radiation from the erbium:yttrium aluminum-garnet (Er:YAG) laser (lambda = 2940 nm), and visible from the 2nd harmonic of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (lambda = 532 nm) on transdermal delivery of 5-aminolevulinic acid (ALA). Pinna skin of the inner side of rabbit ear was used for skin permeation. The light sources were an Er:YAG laser (Key III Plus KaVo) and a Q-switched Nd:YAG laser (Lotis TII SL-2132). Permeation study, morphological and structural skin examination by histology and differential scanning calorimetry (DSC) were carried out. Permeation profiles and histological observations obtained after irradiation with infrared and visible laser radiation differed due to different biophysical effects on irradiated skin. Wavelength of 2940 nm required lower energy contribution to produce the same level of permeation than visible radiation at 532 nm. Structural analysis by DSC shows a selective impact on the lipidic structure. Laser pretreatment enhanced the delivery of ALA trough the skin by SC ablation. PMID- 20589949 TI - Preparation of uniform-sized multiple emulsions and micro/nano particulates for drug delivery by membrane emulsification. AB - Much attention has in recent years been paid to fine applications of drug delivery systems, such as multiple emulsions, micro/nano solid lipid and polymer particles (spheres or capsules). Precise control of particle size and size distribution is especially important in such fine applications. Membrane emulsification can be used to prepare uniform-sized multiple emulsions and micro/nano particulates for drug delivery. It is a promising technique because of the better control of size and size distribution, the mildness of the process, the low energy consumption, easy operation and simple equipment, and amendable for large scale production. This review describes the state of the art of membrane emulsification in the preparation of monodisperse multiple emulsions and micro/nano particulates for drug delivery in recent years. The principles, influence of process parameters, advantages and disadvantages, and applications in preparing different types of drug delivery systems are reviewed. It can be concluded that the membrane emulsification technique in preparing emulsion/particulate products for drug delivery will further expand in the near future in conjunction with more basic investigations on this technique. PMID- 20589950 TI - Microtubule ionic conduction and its implications for higher cognitive functions. AB - The neuronal cytoskeleton has been hypothesized to play a role in higher cognitive functions including learning, memory and consciousness. Experimental evidence suggests that both microtubules and actin filaments act as biological electrical wires that can transmit and amplify electric signals via the flow of condensed ion clouds. The potential transmission of electrical signals via the cytoskeleton is of extreme importance to the electrical activity of neurons in general. In this regard, the unique structure, geometry and electrostatics of microtubules are discussed with the expected impact on their specific functions within the neuron. Electric circuit models of ionic flow along microtubules are discussed in the context of experimental data, and the specific importance of both the tubulin C-terminal tail regions, and the nano-pore openings lining the microtubule wall is elucidated. Overall, these recent results suggest that ions, condensed around the surface of the major filaments of the cytoskeleton, flow along and through microtubules in the presence of potential differences, thus acting as transmission lines propagating intracellular signals in a given cell. The significance of this conductance to the functioning of the electrically active neuron, and to higher cognitive function is also discussed. PMID- 20589951 TI - Perceptual qualia and local network behavior in the cerebral cortex. AB - This paper explores the implications of a recently published theory that relates the experience of qualia to the attractor activity in networks of pyramidal cells in the cerebral cortex. The paper builds on this theory, and aims to link activity in different networks to the nature of the qualia experienced. Some basic links between network activity and qualia experiences are initially presented, showing the importance of learning, and the paper then proceeds to relate these mechanisms to the qualia experienced during sensory perception. The paper argues that attractor behavior in networks of layer 2/3 pyramidal neurons could underpin the vivid sensory qualia of perception, and attractor behavior in networks of layer 5A pyramidal neurons could have a role in the more understanding kind of perceptual qualia. Communication between these networks is explored to suggest their involvement in putting incoming sensory information into the context of all prior experience, and the understanding that could result. PMID- 20589952 TI - A natural science approach to consciousness. AB - We begin with premises about natural science, its fundamental protocols and its limitations. With those in mind, we construct alternative descriptive models of consciousness, each comprising a synthesis of recent literature in cognitive science. Presuming that consciousness arose through natural selection, we eliminate the subset of alternatives that lack selectable physical phenotypes, leaving the subset with limited free will (mostly in the form of free won't). We argue that membership in this subset implies a two-way exchange of energy between the conscious mental realm and the physical realm of the brain. We propose an analogy between the mental and physical phases of energy and the phases (e.g., gas/liquid) of matter, and a possible realization in the form of a generic resonator. As candidate undergirdings of such a system, we propose astroglial pyramidal cell and electromagnetic-field models. Finally, we consider the problem of identification of the presence of consciousness in other beings or in machines. PMID- 20589953 TI - Matching and selection of a specific subjective experience: conjugate matching and experience. AB - We incorporate the dual-mode concept in our dual-aspect PE-SE (proto-experience subjective experience) framework. The two modes are: (1) the non-tilde mode that is the physical (material) and mental aspect of cognition (memory and attention) related feedback signals in a neural-network, which refers to the cognitive nearest past approaching towards present; and (2) the tilde mode that is the material and mental aspect of the feed-forward signals due to external environmental input and internal endogenous input, which pertains to the nearest future approaching towards present and is a entropy-reversed representation of non-tilde mode. Furthermore, one could argue that there are at least five sub pathways in the stimulus-dependent feed-forward pathway and cognitive feedback pathway for information transfer in the brain dynamics: (i) classical axonal dendritic neural sub-pathway including electromagnetic information field sub pathway; (ii) quantum dendritic-dendritic microtubule (MT) (dendritic webs) sub pathway; (iii) Ca(++)-related astroglial-neural sub-pathway; (iv) (a) the sub pathway related to extrasynaptic signal transmission between fine distal dendrites of cortical neurons for the local subtle modulation due to voltages created by intradendritic dual-aspect charged surface effects within the Debye layer around endogenous structures such as microtubules (MT) and endoplasmic reticulum (ER) in dendrites, and (b) the sub-pathway related to extracellular volume transmission as fields of neural activity for the global modulation in axonal-dendritic neural sub-pathway; and (v) the sub-pathway related to information transmission via soliton propagation. We propose that: (i) the quantum conjugate matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related more to the mental aspect of the quantum microtubule-dendritic-web and less to that of the non-quantum sub pathways; and (ii) the classical matching between experiences in the mental aspect of the tilde mode and that of the non-tilde mode is related to the mental aspect of the non-quantum sub-pathways (such as classical axonal-dendritic neural sub-pathway). In both cases, a specific SE is selected when the tilde mode interacts with the non-tilde mode to match for a specific SE, and when the necessary ingredients of SEs (such as the formation of neural networks, wakefulness, re-entry, attention, working memory, and so on) are satisfied. When the conjugate match is made between the two modes, the world-presence (Now) is disclosed. The material aspects in the tilde mode and that in the non-tilde mode are matched to link structure with function, whereas the mental aspects in the tilde mode and that in the non-tilde mode are matched to link experience with structure and function. PMID- 20589954 TI - By the way, doctor. I take a fiber supplement, but have heard that I shouldn't be taking it at the same times as medication. How far apart should I take fiber and medicines such as Plavix and Crestor? PMID- 20589955 TI - By the way, doctor. Why are parents not being urged to get their son vaccinated for HPV? PMID- 20589956 TI - Going steady. PMID- 20589957 TI - Some leniency on heart rate control in atrial fibrillation. PMID- 20589958 TI - Get help with a huge medical bill. PMID- 20589959 TI - Ask the doctor. I heard somewhere that the type of earwax you have is linked to your risk of heart disease. Can that be true? PMID- 20589960 TI - Ask the doctor. I am a 59-year-old man. The results of my latest blood test showed that my LDL cholesterol was 67, which was flagged as low. (I do not take any cholesterol-lowering drugs.) Should I be worried, or do anything to raise my LDL? PMID- 20589961 TI - By the way, doctor. When I attempt to go into the outdoor pool at my beach club, I gasp for breath, get dizzy and light-headed, and have to get out. Several years ago, I read an article that some people who are very sensitive to cold water may sustain a heart attack from submersion into cold water. Is this a possibility? PMID- 20589962 TI - By the way, doctor. Do you know anything about the various fancy salts? I've heard that they deliver salt flavor but have a smaller dose of harmful sodium. PMID- 20589963 TI - By the way, doctor. I'm in my mid-80s and am infected with H. pylori, the "ulcer bacteria." I don't have any symptoms and have heard that half of everyone over age 60 tests positive for H. pylori and that many people never develop ulcers. Do I need to be treated? PMID- 20589964 TI - Shellfish for the heart? PMID- 20589965 TI - Ask the doctor. What can be done for endothelial dysfunction that causes coronary artery spasms and requires nitroglycerin at least four times a day? PMID- 20589966 TI - Influenza-associated pneumonia in children hospitalized with laboratory-confirmed influenza, 2003-2008. AB - BACKGROUND: Pneumonia is one of the most common complications in children hospitalized with influenza. We describe hospitalized children with influenza associated pneumonia and associated risk indicators. METHODS: Through Emerging Infections Program Network population based surveillance, children aged <18 years hospitalized with laboratory confirmed influenza with a chest radiograph during hospitalization were identified during the 2003-2008 influenza seasons. A case with radiologically confirmed influenza-associated pneumonia was defined as a child from the surveillance area hospitalized with: (1) laboratory-confirmed influenza and (2) evidence of new pneumonia on chest radiograph during hospitalization. Hospitalized children with pneumonia were compared with those without pneumonia by univariate and multivariate analysis. RESULTS: Overall, 2992 hospitalized children with influenza with a chest radiograph were identified; 1072 (36%) had influenza-associated pneumonia.When compared with children hospitalized with influenza without pneumonia, hospitalized children with influenza-associated pneumonia were more likely to require intensive care unit admission (21% vs. 11%, P < 0.01), develop respiratory failure (11% versus 3%, P < 0.01), and die(0.9% vs. 0.3% P 0.01). In multivariate analysis, age 6 to 23 months(adjusted OR: 2.1, CI: 1.6 -2.8), age 2 to 4 years (adjusted OR: 1.7, CI:1.3-2.2), and asthma (adjusted OR: 1.4, CI: 1.1-1.8) were significantly associated with influenza-associated pneumonia. CONCLUSIONS: Hospitalized children with influenza-associated pneumonia were more likely to have a severe clinical course than other hospitalized children with influenza, and children aged 6 months to 4 years and those with asthma were more likely to have influenza associated pneumonia.Identifying children at greater risk for influenza associated pneumonia will inform prevention and treatment strategies targeting children at risk for influenza complications. PMID- 20589967 TI - Hormonally driven. PMID- 20589968 TI - Pushing on through. PMID- 20589969 TI - Don't let sleeping cells lie. PMID- 20589970 TI - An unhelpful hand. PMID- 20589971 TI - We bonded--now make a decision. PMID- 20589972 TI - It's the CpG content that counts. PMID- 20589973 TI - Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload. AB - OBJECTIVES: In a pressure overload model, sympathetic activity is augmented in response to salt intake. Mineralocorticoid receptors and epithelial Na channels (ENaCs) are thought to contribute to Na-processing, but the underlying mechanism is unknown. Here, we investigated the contribution of the brain mineralocorticoid receptor- ENaC pathway to salt-induced sympathetic activation in a pressure overload model. METHODS AND RESULTS: Aortic banding was performed to produce a mouse pressure overload model. Four weeks after aortic banding (AB-4), left ventricular (LV) wall thickness was increased without a change in percentage fractional shortening (%FS). Sympathetic activity increased in response to a 5 day high-salt diet in AB-4, but not in Sham-4. Brain mineralocorticoid receptor, alphaENaC, and angiotensin II type 1 receptor (AT1R) expression levels were greater in AB-4 than in Sham-4. The increase in sympathetic activity and in the expression of these proteins was blocked by intracerebroventricular (ICV) infusion of eplerenone, a mineralocorticoid receptor blocker. In another protocol, AB-4 mice were fed a high-salt diet (AB-H) for 4 additional weeks. At 4 weeks, %FS was decreased and sympathetic activity was increased in AB-H compared with Sham. Expression of mineralocorticoid receptors and AT1R in the brain was higher in AB-H than in Sham. ICV infusion of eplerenone in AB-H attenuated salt induced sympathoexcitation and the decreased %FS. ICV infusion of eplerenone also decreased brain AT1R expression. CONCLUSIONS: These findings indicate that activation of brain alphaENaC and AT1R through mineralocorticoid receptors contributes to the acquisition of Na sensitivity to induce sympathoexcitation. Therefore, high salt intake accelerates sympathetic activation and LV systolic dysfunction in a pressure overload model. PMID- 20589974 TI - Adding more to the Myc story. PMID- 20589975 TI - Pattern of expression of inflammatory markers in adipose tissue of untreated hypertensive patients. AB - OBJECTIVE: Adiposity contributes to the insulin resistance and endothelial dysfunction of the hypertensive state; the inflammatory network and the metalloprotease (MMP)/ tissue inhibitor of metalloprotease (TIMP) system modulate vascular structure and function. METHODS: We measured interleukin-6 (IL-6); plasminogen activator inhibitor-1 (PAI-1); tumor necrosis factor-alpha; transforming growth factor-beta; MMP-2, MMP-9, TIMP-1, and TIMP-2 expression; MMP 2 and MMP-9 activity; and TIMP-1 and TIMP-2 protein in adipocytes isolated from paired samples of visceral and subcutaneous adipose tissue of 30 nonobese, untreated hypertensive patients and 20 normotensive controls. RESULTS: Although expression of IL-6, PAI-1, tumor necrosis factor-alpha, and transforming growth factor-beta were generally higher in visceral adipocytes, IL-6, PAI-1, and tumor necrosis factor-alpha were overexpressed, and transforming growth factor-beta was underexpressed in hypertensive vs. controls (all P<0.0001). These changes were paralleled by higher circulating IL-6 and PAI-1 levels in hypertensive patients. MMP-2 and TIMP-2 expression - which were higher in subcutaneous than visceral cells - were reduced in hypertensive patients (all P<0.0001), whereas MMP-9 and TIMP-1 did not differ between the two groups. Both MMP-2 and MMP-9 activity were reduced in hypertensive patients (all P<0.0001). In the whole dataset, SBP and DBP were directly related to IL-6 and PAI-1 expression and inversely to MMP-2 and MMP-9 activity. CONCLUSION: Adipocytes from both visceral and subcutaneous depots of untreated hypertensive patients show a pattern of expression of inflammatory and MMP/TIMP molecules that is compatible with the raised circulating levels of inflammatory markers, is quantitatively related to the height of blood pressure, and provides the cellular basis for the proinflammatory and prothrombotic predisposition of these patients. PMID- 20589976 TI - Clinical and epidemiologic characteristics of children hospitalized with 2009 pandemic H1N1 influenza A infection. AB - BACKGROUND: In 2009, pandemic H1N1 influenza caused significant morbidity and mortality worldwide. We describe the clinical and epidemiologic characteristics of children and adolescents hospitalized for 2009 H1N1 infections in Milwaukee, Wisconsin from April 2009 to August 2009. METHODS: We conducted retrospective chart reviews of hospitalized patients with laboratory-confirmed 2009 H1N1 infections. Data on financial burden associated with these infections were obtained and analyzed. RESULTS: A total of 75 children hospitalized for 2009 pandemic H1N1 infections were identified; the median age was 5 years (range, 2 months-19.2 years); 56% were males; 56% were Non-Hispanic Blacks; and 75%had at least one underlying medical condition. Twenty-four percent had only upper respiratory symptoms. Bacterial coinfections occurred in 1.3%.All but one patient received antivirals, 80% of patients received antibacterials,18.6% were admitted to the intensive care unit, 6% required mechanical ventilation, 2.6% required extracorporeal membrane oxygenation,and 2.6% died. The total charges incurred for H1N1 influenza hospitalizations were $4,454,191, with individual charges being highest for children > 12 years of age. CONCLUSIONS: The majority of children with pandemic H1N1 influenza associated hospitalizations had uncomplicated illness despite the frequent presence of high-risk conditions in our patient population. Laboratory confirmed 2009 pandemic H1N1 influenza hospitalizations resulted in substantial health care and economic burden during the first wave of the pandemic in spring 2009. PMID- 20589977 TI - Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation. AB - BACKGROUND: Persistence and development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of atrial fibrillation compared with regression or continued absence of LVH. We postulated that this association might be in part mediated via greater left atrial enlargement (LAE) in patients with new and persistent ECG LVH. METHODS AND RESULTS: Baseline and third year ECG LVH and left atrial systolic diameter were examined in 663 patients in the Losartan Intervention For Endpoint reduction in hypertension echocardiographic substudy who were in sinus rhythm at baseline and had no history of atrial fibrillation. Left atrial systolic diameter was measured and considered enlarged if more than 3.8 cm in women or more than 4.2 cm in men. Cornell product LVH above 2440 mm-ms was considered consistent with LVH. After 3 years follow-up, 238 patients (35.9%) had continued absence of Cornell product LVH, 156 (23.5%) had regression of LVH, 236 (35.6%) had persistent LVH and 33 patients (5.0%) developed new ECG LVH. Compared with third year mean left atrial systolic dimension and prevalence of LAE in patients with continued absence of LVH (3.62+/-0.52 cm, 12.6%), there were step-wise increases in patients with regression of LVH (3.71+/-0.49 cm, 20.5%), persistence of LVH (3.82+/-0.57 cm, 32.2%) and development of new ECG LVH (3.91+/-0.42 cm, 36.4%, both P<0.001). After controlling for differences in age, sex, baseline SBP, BMI and Sokolow-Lyon voltage, randomized treatment allocation, change in DBP and SBP between baseline and third year and for isovolumic relaxation time and presence of an abnormal mitral E/A ratio at baseline and third year, the odds of having LAE were significantly increased in patients with persistent LVH (odds ratio 1.8, 95% confidence interval 1.1-3.2, P=0.043) or new LVH (odds ratio 3.1, 95% confidence interval 1.3-7.7, P=0.016), but not in patients with regression of Cornell product LVH (odds ratio 1.1, 95% confidence interval 0.6-2.0, P=0.860). CONCLUSION: Persistence or development of new ECG LVH during antihypertensive therapy are associated with an increased risk of LAE after 3-year follow-up, whereas regression of ECG LVH is not associated with an increased risk of LAE. These findings provide insight into a possible mechanism by which changes in ECG LVH are associated with changing risk of developing atrial fibrillation. PMID- 20589978 TI - Effects of suboptimal doses of the AT1 receptor blocker, telmisartan, with the angiotensin-converting enzyme inhibitor, ramipril, on cerebral arterioles in spontaneously hypertensive rat. AB - OBJECTIVE: Antihypertensive treatment with standard clinical doses of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) reverses cerebral arteriolar remodeling, thus restoring dilatation and the lower limit of cerebral blood flow (CBF) autoregulation (LL CBF AR). In humans, a combination of standard clinical doses of the two drugs does not produce greater protection against stroke than that obtained with single-drug treatments and increases the risk of side-effects. We hypothesized that a combination of suboptimal doses of the ARB, telmisartan (TEL) and of the ACEI, ramipril (RAM), could be a well tolerated and effective treatment of hypertension-induced remodeling of cerebral arterioles. DESIGN: We studied the impact of 3-month oral treatment with TEL (0.5 or 0.8 mg/kg per day) or RAM (0.1 or 0.25mg/ kg per day) alone or in combination (TEL0.8 + RAM0.1 or TEL0.5 + RAM0.25) on the cerebral circulation of the spontaneously hypertensive rats (SHRs). Normotensive Wistar Kyoto rats (WKYs) were taken as controls. METHODS: Cerebral arteriolar pressure, CBF and internal diameter were measured via an open-skull preparation at baseline and during hypotension before and after deactivation (EDTA). RESULTS: Combinations normalized cerebral arteriolar pressure, whereas drugs alone had no significant impact. TEL0.8 + RAM0.1 showed the greatest effect on arteriolar internal diameter (SHRs 42+/-16, WKYs 59+/-16microm, TEL0.5 + RAM0.25 50+/-6, TEL0.8 + RAM0.1 62+/-18, P<0.05) and normalized LL CBF AR (SHRs 77+/-28, WKYs 53+/-17 mmHg, TEL0.8 + RAM0.1 50+/-10, P<0.05). CONCLUSION: The combination of suboptimal doses of TEL and RAM with an 8 : 1 ratio has the greatest effect on cerebral circulation and could represent well tolerated and efficient treatment of cerebral ischemia and stroke. PMID- 20589979 TI - Implementing the delayed antibiotic therapy approach significantly reduced antibiotics consumption in Israeli children with first documented Acute otitis media. AB - BACKGROUND: In 2004, the Israel Medical Association issued guidelines recommending delaying antibiotic therapy for non severe acute otitis media(AOM) in children aged > or = 6 months for 24 to 48 hours, using analgesics for symptomatic relief instead. We assessed the effect of these guidelines on antibiotic use associated with AOM in an Israeli health maintenance organization. METHODS: We conducted a retrospective study of pharmacy purchasing and physician visit data between the years 2002 and 2007. The study population included children aged 6 months to 5 years who were diagnosed with a first episode of AOM and had not been treated with antibiotics within the proceeding month. For each calendar year data we analyzed the following:(1) annual incidence of first episode of AOM, (2) rate of antibiotic treatment, and (3) rate of topical treatment for pain relief. Comparisons were made among the years for the total population and for age groups 0.5 to 1, 1 to 2, and 2 to 5 years. RESULTS: The eligible study population ranged from 154,961 children in 2002 to 158,971 in 2007. Between 2002 and 2004, the rate of antibiotic treatment for first documented AOM increased from 53% to 61% in children aged 6 months to 1 year, 56% to 63% among children aged 1 to 2 years, and 51% to 56% of children aged 2 to 5 years (P < 0.001). Between 2004 and 2007, treatment rates decreased from 61% to 54%, 63% to 54%, and 56% to 47%, respectively(P < 0.001). Proportions of cases treated exclusively with topical therapy increased between 2004 and 2007 from 5% to 9%, 4% to 8%, and 8 to 14%for the respective categories (P < 0.001). CONCLUSIONS: Implementation of the delayed antibiotic treatment approach was associated with a significant reduction in use of antibiotics associated with first documented AOM in children aged 6 months to 5 years, reversing an upward trend that occurred previously. PMID- 20589980 TI - Reduction in hospitalizations for pneumonia associated with the introduction of a pneumococcal conjugate vaccination schedule without a booster dose in Australia. AB - BACKGROUND: Postmarketing surveillance of heptavalent pneumococcal conjugate vaccine (7vPCV) has shown significant reductions in admissions coded as pneumonia in countries where a booster dose is given in the second year of life. In Australia, a 3-dose primary schedule at 2, 4, and 6 months of age without a booster has been funded nationally for non-Indigenous children since 2005. METHODS: All hospital discharges in Australia with the primary diagnosis coded as pneumonia between July 1998 and June 2007 were identified from a national electronic database. Monthly rates of hospitalization for pneumonia over this period were determined for the age groups < 2, 2-4,5-17, 18-39, 40-64, and > or = 65 years. Negative binomial regression modeling,adjusting for background and seasonal trends, was used to quantify the effect of the 7vPCV program. RESULTS: A total of 523,591 eligible hospital discharges were identified. In the 30 months following 7vPCV introduction, there were significant adjusted reductions in all cause pneumonia in children aged < 2 and 2 to 4 years of 38%(95% CI 36%-40%), and 29% (26%-31%), respectively. Reductions of between 3% and 11% were observed in the older age groups. INTERPRETATION: The significant differential effects observed are strongly suggestive of the PCV7 program being responsible for the observed reduction in pneumonia hospitalizations in Australia, and the magnitude was comparable to that documented in countries with a booster dose. This finding appears robust and may be related to high levels of vaccination coverage and catch-up early in the program, or to relatively lower levels of serotype replacement without a booster dose. PMID- 20589981 TI - Longitudinal changes in carotid intima-media thickness and cardiovascular risk factors in human immunodeficiency virus-infected children and young adults compared with healthy controls. AB - OBJECTIVES: HIV-infected patients are at increased risk of cardiovascular disease (CVD). This study assessed longitudinal changes in carotid intima-media thickness (cIMT) as a surrogate marker for CVD, and determined the relationship between cIMT and cardiovascular risk factors in HIV infected children/young adults. METHODS: This was a longitudinal, observational study comparing cIMT,fasting metabolic profile, and C-reactive protein in HIV-infected subjects 2 to 21 years old to matched controls at baseline and 48 weeks. RESULTS: Thirty-five HIV + subjects and 37 controls were included in the analysis. Among HIV + subjects, the median age was 10 years, body mass index was 18.7 kg/m2, 37% were male, CD4 count was 32%, 77% had HIV-RNA 400 copies/mL, and 86% were on antiretrovirals. At baseline,HIV + had higher lipids and C-reactive protein. HIV-infected had higher internal carotid artery (ICA) and common carotid artery (CCA) IMT (mm)(ICA: HIV + , 0.90; controls, 0.78 [P = 0.01]; CCA: HIV + , 1.00; controls,0.95 [P = 0.05]). At 48 weeks, CD4% increased and low-density lipoprotein decreased in HIV-infected subjects. ICA and CCA median changes for HIV-infected subjects were -0.23 and 0.15 mm, respectively (both P 0.01). In controls, only CCA changed (P = 0.04). Between-group changes were not significant, except when only 31 perinatally infected HIV - subjects and the controls were compared (CCA P = 0.04). In multiple regression analyses of HIV + subjects, antiretroviral therapy duration and CD4% were associated with cIMT changes. CONCLUSIONS: Higher cIMT was found in HIV-infected subjects than in healthy controls, but at 48 weeks, cIMT was similar between groups. These data suggest that HIV-infected children/young adults are at high risk of CVD, but lipid control, immune restoration, and viral suppression with continuous antiretroviral therapy may prevent its worsening. PMID- 20589982 TI - An outbreak of necrotizing enterocolitis associated with norovirus genotype GII.3. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is an acute abdominal emergency of unknown etiology predominantly affecting preterm infants. We describe a cluster of NEC in a level III NICU involving 15 infants over a6-month period. Cohorting and stringent infection control measures were associated with termination of the cluster. A case-control study was used to investigate potential risk factors associated with development of NEC. METHODS: Stool samples were collected from 55 infants (10 of 15 NEC and 45 non-NEC controls). Enteric pathogens were identified by culture and/or molecular diagnostic techniques. For the case-control study, controls were selected from admitted neonates during the same time and in the preceding 6-month period, matched for gestation and birthweight. RESULTS: Forty percent (4/10) of NEC infants had norovirus RNA detected compared with 9% (4/45) of non-NEC infants (OR: 6.83, 95% CI: 1.3-34.9,P = 0.021). A lower rate of prolonged rupture of membranes and a higher rate of maternal smoking was also observed in NEC infants than in controls. No significant differences in incidences of chorioamnionitis, intrapartum antibiotics,volume of feedings, time of first formula feeding, and rates of patent ductus arteriosus or intrauterine growth retardation were detected. CONCLUSIONS: Infants who developed NEC had an increased incidence of norovirus detection in their stool following diagnosis. This further strengthens the case for an etiologic role of norovirus in the pathogenesis of NEC. PMID- 20589984 TI - Low risk of bacteremia in otherwise healthy children presenting with fever and severe neutropenia. AB - We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxoplasma was detected in 16 placentas,including 1 in which congenital toxoplasmosis was ruled out. Placental screening had poor sensitivity (25%) but good specificity (99%), positive predictive value (93%), and negative predictive value (95%). PMID- 20589985 TI - [Oscillatory character of carbon metabolism in photosynthesis: arguments and facts]. AB - Plentiful experimental data on the primary photosynthetic assimilates, concerning mainly the carbon isotopic composition, were summarized. These data are considered based on the photosynthetic oscillatory model, according to which photosynthesis is an oscillatory process consisting of the CO2 assimilation phase and the photorespiration phase. All the data considered and the results of numerical modeling are in agreement, thus confirming the validity of the model. They allow us to affirm the existence of sustained photosynthetic oscillations. PMID- 20589987 TI - A life-history model of human fitness indicators. AB - Recent adaptationist accounts of human mental and physical health have reinvigorated the debate over the evolution of human intelligence. In the tradition of strong inference the current study was developed to determine whether either Miller's (1998, 2000a) Fitness Indicator Theory or Rushton's (1985, 2000) Differential-K Theory better accounts for general intelligence ("g") in an undergraduate university population (N=192). Owing to the lengthy administration time of the test materials, a newly developed 18-item short form of the Ravens Advanced Progressive Matrices (APM-18; Sefcek, Miller, and Figueredo 2007) was used. A significant, positive relationship between K and F (r = .31, p < .001) emerged. Contrary to predictions, no significant relationships were found between "g" and either K or F (r = -.09, p > or = .05 and r = .11, p > or = .05, respectively). Though generally contrary to both hypotheses, these results may be explained in relation to antagonistic pleiotropy and a potential failure to derive correct predictions for within-species comparisons directly from the results of between-species comparisons. PMID- 20589986 TI - Variation in the trajectories of depressive symptoms: results from the Americans' Changing Lives Study. AB - This study examines the association between race and depressive symptoms over a 16-year study period. The analysis is based on the responses of 3485 African American and White respondents from four waves of the Americans' Changing Lives Panel Study. Growth mixture modeling was used to identify latent trajectory classes based on the reported levels of depressive symptoms over 16 years. Four latent trajectory classes were identified: two "high-risk" groups and two "low risk" groups. Findings show the heterogeneity among and within racial groups in their trajectories of depressive symptoms and the distinct demographic and social relationship predictors for symptom trajectories. PMID- 20589988 TI - Significant effects of Fatwa-based perception on contraceptive practice among Muslim women in south Jordan under the early stage of fertility transition. AB - An interview survey of 450 Muslim women in a rural village of south Jordan under the early stage of fertility transition was conducted to explore major causes of contraceptive use, taking both their sociodemographic attributes and fatwa (Islamic jurisprudence)-based perception into account. Discriminant analysis, which was performed for the subject women divided into 15- to 29-, 30- to 39-, and 40- to 49-year age groups, revealed that "the number of living children" in the former and "to do contraception for good care of children" in the latter played significant roles in discrimination into contraceptive user and nonuser groups for any age groups. To cope with demographically and socioeconmically vulnerable situations, contraceptive prevalence rate should be increased by means of government-led family planning programs in cooperation with the imam (Muslim religious leaders and priests) through fatwa, in which special attention is paid to traditional norms, represented by good childcare. PMID- 20589989 TI - Educational degrees and adult mortality risk in the United States. AB - We present the first published estimates of U.S. adult mortality risk by detailed educational degree, including advanced postsecondary degrees. We use the 1997 2002 National Health Interview Survey (NHIS) Linked Mortality Files and Cox proportional hazards models to reveal wide graded differences in mortality by educational degree. Compared to adults who have a professional degree, those with an MA are 5 percent, those with a BA are 26 percent, those with an AA are 44 percent, those with some college are 65 percent, high school graduates are 80 percent, and those with a GED or 12 or fewer years of schooling are at least 95 percent more likely to die during the followup period, net of sociodemographic controls. These differentials vary by gender and cohort. Advanced educational degrees are associated not only with increased workforce skill level but with a reduced risk of death. PMID- 20589990 TI - Inflammation: Hope for sepsis treatment. PMID- 20589991 TI - Regulatory T cells: Nurtured by TGFbeta. PMID- 20589993 TI - It's never too late to quit smoking. PMID- 20589992 TI - Cut salt for resistant hypertension. PMID- 20589994 TI - Interview with Marc Ferrer, Ph.D.. Interview by Vicki Glaser. PMID- 20589995 TI - Lack of sex affects the heart. PMID- 20589996 TI - Ask the doctor. Six months after having my knee replaced (at age 88!), I developed a cardiac arrhythmia. I know of this happening to several other people, including a friend who developed an arrhythmia two months after having his hip replaced at age 76. Does joint replacement surgery often cause heart rhythm problems? PMID- 20589997 TI - Cardiac device therapy in elderly patients--insights from 'real world' practice. PMID- 20589998 TI - New d-dimer cut-off value helps rule out pulmonary embolism in the elderly. PMID- 20589999 TI - Elevated systolic blood pressure in middle age is associated with late-life dementia. PMID- 20590000 TI - Continuous-flow LVAD improves quality of life. PMID- 20590001 TI - Massive haemoptysis and pulmonary arterial pseudoaneurysm in a patient with unrepaired tetralogy with pulmonary atresia. PMID- 20590002 TI - Rare complications after Fontan operation. PMID- 20590003 TI - Successful thrombolysis of massive intracardiac thrombus in atriopulmonary Fontan circulation. PMID- 20590004 TI - Breastfeeding and CMPA. PMID- 20590005 TI - American ideal. You, too, can be a star where it counts--in the heart. PMID- 20590006 TI - Exercise stress test. The treadmill test can reveal hidden problems in the heart. PMID- 20590007 TI - A personal approach to heart failure. Following a self-care plan can keep you healthy and out of the hospital. PMID- 20590008 TI - Taming a killer. Heart attacks aren't nearly as deadly as they used to be. PMID- 20590009 TI - Dual protection: 6 steps for preventing dementia. PMID- 20590010 TI - Ask the doctor. I am 95 years old and recently began treatment for early macular degeneration in one eye. My retinologist said that PreserVision might help protect the other eye. But she cautioned that it contains a large dose of vitamin E, which could cause a bleeding problem with the Coumadin I take because of a mechanical aortic valve. What would you suggest? PMID- 20590011 TI - Ask the doctor. Some friends invited me to accompany them to Rocky Mountain National Park. I would love to go, but I have high blood pressure and worry that high altitudes are dangerous for people with this condition. Is this the case? PMID- 20590012 TI - New Zealand Society of Gastroenterology statement on the use of biological therapy in inflammatory bowel disease. PMID- 20590014 TI - [Imaging diagnosis of Crohn disease]. AB - Improvements in the ultrasound examination of bowel disease have registered in the last years the introduction of new technologies regarding high frequency probes (US), highly sensitive color or power Doppler units (CD-US), and the development of new non-linear technologies that optimize detection of microbubbles contrast agents responses. Contrast-enhanced ultrasound (CE-US) most importantly increases the results in sonographic evaluation of Crohn disease inflammatory activity. CE-US has become an imaging modality routinely employed in the clinical practice for the evaluation of parenchymal organs due to the introduction of new generation microbubble contrast agents which persist in the bloodstream for several minutes after intravenous injection. The availability of high frequency dedicated contrast-specific US techniques provide accurate depiction of small bowel wall perfusion due to the extremely high sensitivity of non-linear signals produced by microbubble insonation. In Crohn's disease, CE-US may characterize the bowel wall thickness by differentiating fibrosis from edema and may grade the inflammatory disease activity by assessing the presence and distribution of vascularity within the layers of the bowel wall (submucosa alone or the entire bowel wall). Peri-intestinal inflammatory involvement can be also characterized. CE-US can provide prognostic data concerning clinical recurrence of the inflammatory disease and evaluate the efficacy of drugs treatments. PMID- 20590015 TI - [Incidental thyroid carcinoma: a multicentric experience]. AB - BACKGROUND: In recent years it has seen an increase of incidental thyroid carcinomas (ICs), most of the ICs are any microcarcinoma (MC). The term refers to a CT, predominantly papillary, and smaller than or equal to 1 cm. The MC is characterized by a papillary heterogeneous clinical behavior ranging from small outbreak discovered accidentally after surgery than the cancer that manifests clinically with lymph node metastases in the neck or rarely systemic. METHODS: From January 2007 to June 2009, 1507 patients for benign disease were subjected to surgery. RESULTS: Histological examination confirmed the diagnosis of benignity in 1339 cases. In 168, however, we detected unexpected, incidental carcinoma (CI). In patients with CI receiving total surgery (TT), the next iteration we agree with the endocrinologist. In cases of lobectomia, was run TT and was heading endocrinology. Of the 168 patients with incidental CT, 147 had papillary carcinomas, 12 follicular carcinomas, 5 follicular variant papillary carcinomas, 2 oncocytic carcinomas, 1 uncertain malignancy. CONCLUSION: In our study has highlighted the lack of data (medical history, ultrasound, scintigraphic), they may portend the presence of a tumor in the specimen CI. In all patients with CI, the surgical indication was given for symptomatic disease, for impairment of thyroid function, for failure to respond to medical therapy or unable to continue. The IC is almost always a microcarcinoma, predominantly papillary, and smaller than or equal to 1 cm, has little biological aggressiveness and is susceptible to metabolic radioiodine therapy. On the basis of these data we feel reasonably acceptable to a close follow-up endocrine surgery, particularly in patients with multinodular disease and stress the need for a multi-specialized team. PMID- 20590016 TI - [Acute hemorrhagic syndrome by lupus anticoagulant]. AB - Antiphospholipid antibodies are correlated to antiphospholipid syndrome, that is characterized by one or more thrombotic episodes and obstetric complications. Some recent studies have evidenced as antiphospholipid antibodies can be correlated to an transitory hemorrhagic syndrome with prolonged aPTT. This syndrome compares 7-10 days after a bacterial or viral infection and it is characterized by a spontaneous regression into a period of three months. The aim of this paper is to evidence the pathogenesis and the clinical aspects of this syndrome. PMID- 20590017 TI - [Vitamin D deficiency and cardiovascular diseases]. AB - The increasing worldwide displacement from the natural outdoor environment of human beings to an indoor sedentary lifestyle, along with the recommendation to avoid any direct sun exposure because of the risk of skin cancer, has resulted in a global pandemic of vitamin D insufficiency. Traditionally, vitamin D has been associated primarily with bone health. However, it has become evident that adequate vitamin D status is important for optimal function of many organs and tissues throughout the body, including the cardiovascular system. Vitamin D insufficiency seems to predispose to hypertension, diabetes and the metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. The relationship between baseline vitamin D status, dose of vitamin D supplements, and cardiovascular events remains to be investigated by ongoing randomized trials; however increasing evidence suggests that the provision of a simple, well-tolerated, and inexpensive correction of vitamin D insufficiency favourably affects the morbility and mortality of cardiovascular disease along with the prevention of the most common chronic degenerative diseases. PMID- 20590018 TI - [High altitude pulmonary edema: the importance of early diagnosis]. AB - In high altitude setting is present a syndrome linked to hypoxia, exercise and low temperatures, causing multiple organ damage, which may also lead to death. The main clinical pictures are represented by acute mountain sickness, high altitude pulmonary edema (HAPE), high altitude cerebral edema. A clinical case with the main determinants of HAPE, during a trek in the Himalayas valley is described. PMID- 20590019 TI - [46-year-old, veiled patient. Waddeling gait and bone pain]. PMID- 20590020 TI - [RLV (Regulated Performance Volume) and QZV (Qualification Related Additional Volume): setting the course for the 1st of July now!]. PMID- 20590021 TI - [National cancer plan: "We will improve oncologic care"!]. PMID- 20590022 TI - [Supplementing standard oncologic medicine. Sensible use of complementary medicine!]. PMID- 20590023 TI - [Migraine patients do not feel well managed. How do you deal with pain attacks? (interview by Dr. Judith Neumaier)]. PMID- 20590024 TI - [Red mystery]. PMID- 20590025 TI - [Diabetic patient with liver or kidney disease. Which antidiabetics are allowed?]. PMID- 20590026 TI - [Hay fever]. PMID- 20590027 TI - [Bariatric surgery: fighting obesity and diabetes with a scalpel]. PMID- 20590028 TI - [Bariatric surgery from the internist's point of view]. PMID- 20590029 TI - [Surgical therapy of morbid obesity]. PMID- 20590030 TI - [Emergency checklist: rib fractures]. PMID- 20590031 TI - [Leg length difference]. PMID- 20590032 TI - [46-year-old patient with metabolic syndrome: lifestyle changed--patient cured]. PMID- 20590033 TI - [Hepatic encephalopathy. L-ornithine-L-aspartate stimulate detoxification capacity of the liver]. PMID- 20590034 TI - [Preventable problems in thyroid hormone substitution therapy. The risks of brand change are unpredictable]. PMID- 20590036 TI - Degrees will equip nurses to meet future challenges in healthcare. PMID- 20590037 TI - Female catheters cause trauma in males. PMID- 20590038 TI - Everybody matters 2: promoting dignity in acute care through effective communication. AB - The Dignity in Care Project (DCP) aims to deepen understanding and develop practical interventions to promote dignified care in hospitals. A key feature is that "everybody matters" (a project slogan) and that promoting and sustaining dignity in acute care requires recognition and support for staff as well as for patients and their families. DCP is a nurse led research collaboration with Royal Free Hampstead Trust, Barnet and Chase Farm Hospitals Trust and City University. Practical interventions devised by the project are presented around three keythemes. Part 1 of this series explored the first theme, "maintaining identity: see who I am", and this second part examines the second theme, "creating community: connect with me". This recognises that in the act of caring, nurses receive as well as give. Dignified care has a reciprocity where both carer and patient/family give and receive, rather than simply involving a list of practical tasks done t o someone. The third and final part looks at "shared decision making involve me" (Bridges et al, 2009). PMID- 20590039 TI - Meningococcal meningitis manifesting as hydrocephalus: a clinical dilemma. PMID- 20590040 TI - Cancer survivorship 2: providing advice and support to those living with and beyond cancer. AB - The second in this two part unit on cancer survivorship gives practical advice on identifying those with long term and late effects of cancer and its treatment, and providinginformation and support. Part 1 explored why more people are surviving cancer, and how services need to change to meet the needs of this group. PMID- 20590041 TI - Will graduate entry free nursing from the shackles of class and gender oppression? AB - Debates in nursing focus on the provision of good nursing care and its relation to academic status. For example, are nurses "too posh to wash" if they believe entry to the profession should require a degree, or is this a case of them having pretensions "above their station"? This article discusses the nature of oppression and its relationship to hierarchy, and concludes that nurses are oppressed through gender and socioeconomic class. It also examines the profession's social position, arguing thatthe majority of nurses identify with the most oppressed social class. PMID- 20590042 TI - Care of the dying must be part of mandatory training. PMID- 20590043 TI - Get ahead, get a hat? Didn't that go out with the ark? PMID- 20590044 TI - MDS 3.0 promises positive change. PMID- 20590045 TI - Bruce Yarwood reflects on change. PMID- 20590046 TI - Vitamin D: the super drug. PMID- 20590047 TI - A new look at incontinence. PMID- 20590048 TI - Top 50 nursing facility companies. 2010: steady and cautious. PMID- 20590049 TI - Top 40 assisted living chains. 2010: a bright spot. PMID- 20590050 TI - The process is the product: a new model for multisite IRB review of data-only studies. PMID- 20590051 TI - The evolution of consent forms for research: a quarter century of changes. PMID- 20590052 TI - Canadian research ethics boards and multisite research: experiences from two minimal-risk studies. PMID- 20590053 TI - Is your OR leadership team up to health care reform challenges? PMID- 20590054 TI - OR governance builds a strong foundation. PMID- 20590055 TI - Surgery center geared to older adults. PMID- 20590056 TI - Winning converts to SUD reprocessing. PMID- 20590057 TI - Spinal implant costs decline modestly. PMID- 20590058 TI - Integrating devices for patient safety. PMID- 20590059 TI - How do we charge for OR supply packs? PMID- 20590060 TI - Keeping up with ASC credentialing. PMID- 20590061 TI - Joint Commission's toughest elements. PMID- 20590063 TI - More evidence of green tea's effectiveness is needed. PMID- 20590064 TI - Improving sensitivity to patients from other cultures. PMID- 20590065 TI - Hip pain without injury. PMID- 20590066 TI - Prescribing evidence: the efficacy and safety of new drugs. PMID- 20590067 TI - Opioid therapy for chronic noncancer pain. PMID- 20590068 TI - Effectiveness of antidepressants compared with placebo for depression in primary care. PMID- 20590069 TI - Care of the returning veteran. AB - Of the 23.8 million military veterans living in the United States, approximately 3 million have served in Operation Enduring Freedom or Operation Iraqi Freedom. The injuries and illnesses that affect veterans returning from combat are predictable. Blast injuries are common and most often present as mild traumatic brain injury, which is synonymous with concussion. Family physicians caring for returning veterans will also encounter conditions such as posttraumatic stress disorder at rates higher than those in the general population. The symptoms associated with posttraumatic stress disorder and mild traumatic brain injury often overlap and can present concurrently. Treatment of traumatic brain injury should be based on symptoms and guided by clinical practice guidelines from the U.S. Department of Veterans Affairs and Department of Defense. Family physicians should understand the range of post-war health concerns and screen returning service members for posttraumatic stress disorder, substance abuse, suicidality, and clinical depression. Family physicians are well positioned to offer continuity of care for issues affecting returning service members and to coordinate the delivery of specialized care when needed. PMID- 20590070 TI - Veterans: what to expect when you return from deployment. PMID- 20590071 TI - Evaluating the safety and effectiveness of new drugs. AB - Prescribers seek to provide their patients with access to the latest innovations in medicine to maximize their health status. When a new drug comes to market, it often has not been as widely tested as other available therapies, and its effectiveness and safety cannot be fully evaluated. To address this problem, physicians can use the STEPS (Safety, Tolerability, Effectiveness, Price, and Simplicity) mnemonic to provide an analytic framework for making better decisions about a new drug's appropriate place in therapy. A key element is to base this evaluation on patient-oriented evidence rather than accept disease-oriented evidence (which may be misleading), while avoiding inappropriate reliance on studies that report only noninferiority results or relative risk reductions. The primary question to ask for each new drug prescribing decision is, "Is there good evidence that this new drug is likely to make my patient live longer or better compared with the available alternatives?" PMID- 20590072 TI - Safety and effectiveness of new medicines. PMID- 20590073 TI - Gait and balance disorders in older adults. AB - Gait and balance disorders are common in older adults and are a major cause of falls in this population. They are associated with increased morbidity and mortality, as well as reduced level of function. Common causes include arthritis and orthostatic hypotension; however, most gait and balance disorders involve multiple contributing factors. Most changes in gait are related to underlying medical conditions and should not be considered an inevitable consequence of aging. Physicians caring for older patients should ask at least annually about falls, and should ask about or examine for difficulties with gait and balance at least once. For older adults who report a fall, physicians should ask about difficulties with gait and balance, and should observe for any gait or balance dysfunctions. The Timed Up and Go test is a fast and reliable diagnostic tool. Persons who have difficulty or demonstrate unsteadiness performing the Timed Up and Go test require further assessment, usually with a physical therapist, to help elucidate gait impairments and related functional limitations. The most effective strategy for falls prevention involves a multifactorial evaluation followed by targeted interventions for identified contributing factors. Evidence on the effectiveness of interventions for gait and balance disorders is limited because of the lack of standardized outcome measures determining gait and balance abilities. However, effective options for patients with gait and balance disorders include exercise and physical therapy. PMID- 20590074 TI - Pain in the quiet (not red) eye. AB - Although eye pain is often accompanied by redness or injection, pain can also occur with a quiet eye. Pain in a quiet eye can be the first sign of a vision threatening condition, a more benign ophthalmologic condition, or a nonophthalmologic condition. Acute narrow-angle glaucoma is an emergent vision threatening condition that requires immediate treatment and referral to an ophthalmologist. Although most nonophthalmologic conditions that cause eye pain do not need immediate treatment, giant cell (temporal) arteritis requires urgent treatment with corticosteroids. Other vascular conditions, such as carotid artery disease, thrombosis of the cavernous sinus, and transient ischemic attack or stroke, rarely cause eye pain but must be considered. Pain may also be referred from the sinuses or from neurologic conditions, such as trigeminal neuralgia, migraine and cluster headaches, and increased intracranial pressure. The differential diagnosis of eye pain in the quiet eye is extensive, necessitating a systematic and thorough approach. PMID- 20590076 TI - Excitation energy migration processes in self-assembled porphyrin boxes constructed by conjugated porphyrin dimers. AB - meso-Pyridine-appended alkynylene-bridged zinc(II) porphyrin dimers D2 and D4 assemble spontaneously, in noncoordinating solvents such as toluene, into tetrameric porphyrin boxes B2 and B4, respectively. Interestingly, the formation of Bn from Dn leads to the two kinds of self-assembled porphyrin boxes constructed by planar and orthogonal conformers, respectively. Excitation energy migration processes within these assemblies have been investigated in detail by using both steady-state and time-resolved spectroscopic methods. The pump-power dependence on the femtosecond transient absorption decay profiles is directly associated with the excitation energy migration process within the Bn boxes, where the exciton-exciton annihilation time is well-described in terms of the Foster-type incoherent energy hopping model. Consequently, the excitation energy hopping rates in porphyrin boxes constructed by planar and orthogonal conformers have been estimated to be (approximately 1.2 ps)(-1) and (approximately 1 ps)( 1), respectively. Furthermore, the porphyrin boxes constructed by orthogonal conformers show additional slow excitation energy hopping rates of (approximately 12 ps)(-1). Overall, the dihedral angle in the constituent dimers is a key factor to control the energy transfer efficiency for the fabrication of artificial light harvesting complexes using conjugated porphyrin dimer systems. PMID- 20590077 TI - Fluorene-based metal-ion sensing probe with high sensitivity to Zn2+ and efficient two-photon absorption. AB - The photophysical, photochemical, two-photon absorption (2PA) and metal ion sensing properties of a new fluorene derivative (E)-1-(7-(4-(benzo[d]thiazol-2 yl)styryl)-9,9-bis(2-(2-ethoxyethoxy)ethyl)-9H-fluoren-2-yl)-3-(2 (9,10,16,17,18,19,21,22,23,24-decahydro-6H dibenzo[h,s][1,4,7,11,14,17]trioxatriazacycloicosin-20(7H)-yl)ethyl)thiourea (1) were investigated in organic and aqueous media. High sensitivity and selectivity of 1 to Zn(2+) in tetrahydrofuran and a water/acetonitrile mixture were shown by both absorption and fluorescence titration. The observed complexation processes corresponded to 1:1 stoichiometry with the range of binding constants approximately (2-3) x 10(5) M(-1). The degenerate 2PA spectra of 1 and 1/Zn(2+) complex were obtained in the 640-900 nm spectral range with the maximum values of two-photon action cross section for ligand/metal complex approximately (90-130) GM, using a standard two-photon induced fluorescence methodology under femtosecond excitation. The nature of the 2PA bands was analyzed by quantum chemical methods and a specific dependence on metal ion binding processes was shown. Ratiometric fluorescence detection (420/650 nm) provided a good dynamic range (10(-4) to 10(-6) M) for detecting Zn(2+), which along with the good photostability and 2PA properties of probe 1 makes it a good candidate in two photon fluorescence microscopy imaging and sensing of Zn ions. PMID- 20590078 TI - Additive model for the second harmonic generation hyperpolarizability applied to a collagen-mimicking peptide (Pro-Pro-Gly)10. AB - Second harmonic generation (SHG) spectrometry has been recently applied to investigate the structure of proteins and sugars (collagen, myosin, starch, etc.). The interpretation of experimental data at the molecular length-scale remains often qualitative because of the difficulty to model the SHG signal of such large molecules. Simpson and co-workers proposed to estimate the hyperpolarizability of the peptide backbone as the sum of the individual hyperpolarizabilities of the peptide bonds. This article discusses the hyperpolarizabilities obtained using such an additive model for a peptide (Pro Pro-Gly)(10) modeling collagen, for which experimental hyperpolarizabilities have been measured and modeled recently. To investigate possible parameters for the model, we performed time-dependent density functional theory (TDDFT) calculations of the hyperpolarizability of a few molecules containing one peptide bond. In a second step, the additive model is applied. The results produced using different input parameters are compared to each other and to experimental data. For the chosen peptide, the additive model using N-methylacetamide as a building block agrees qualitatively with hyper-Rayleigh scattering data. The results emphasize the need for more reference data to test the additivity hypothesis and the transferability of the parameters to other secondary structure of proteins. PMID- 20590079 TI - Argon solid response upon Rydberg photoexcitation of the NO chromosphore: case of using ab initio potential energy surfaces and comparison to similar studied systems. AB - Molecular dynamics simulations of NO-doped Ar solid upon Rydberg photoexcitation of the impurity have been carried out taking into account angular dependent potential energy surfaces (PESs) in the ground and excited states. To go beyond isotropic potentials simulations, the effects of anisotropy of potentials on the structure, dynamics, and energetics are investigated by taking into account two cases, namely, the whole PESs and the isotropic parts. Results have been compared to those obtained in previous works for similar NO-doped rare gas systems. Radial distribution functions (RDF) for the ground and excited state indicate that for both cases the shell structure of the lattice is kept ordered and is characterized by well-defined bands. No influence of the anisotropy of potentials has been detected in the RDFs since the anisotropy is rather manifested at short distances. The well part, which has been proven to be unimportant for the dynamics in previous works, arises here to be important for the right simulation of the spectrum. In general, our results show a reasonable agreement with respect to the experimental values for the dynamics and energetics when ab initio potentials are used, although better results can be obtained if higher level ab initio PESs are used. PMID- 20590080 TI - Quantification of the singlet-singlet annihilation times of individual bichromophoric molecules by photon coincidence measurements. AB - Singlet-singlet annihilation (SSA) times in individual bichromophoric molecules have been quantified by time-resolved photon coincidence measurements. An analytical expression has been derived to obtain the SSA times from the coincidence histograms. The results have been confirmed by Monte Carlo simulations. SSA was found to be about three times faster than the fluorescence lifetime of the chromophores. Considering the spectral overlap for SSA and for energy transfer from an excited to a ground state chromophore, we conclude that in the weak coupling limit for any arrangement of the two chromophores both processes occur on similar time scales. PMID- 20590081 TI - Structural studies of the water hexamer. AB - In this paper we report the geometries and properties of 24 structural isomers located on the MP2/6-311++g** potential energy surface of the water hexamer. At least 15 structural patterns are located within 3 kcal/mol of the most stable conformation, leading to a very complex potential energy surface, several isomers having significant contributions. A quadratic correlation between the distance from the proton to the center of the hydrogen bond with the distance between oxygen atoms for all clusters is reported. MP2/6-311++g** and CCSD(T)/aug-cc pvdz//MP2/6-311++g** predict different stabilization orderings but are in good agreement for binding energies. Compact structures are energetically favored by electronic energies with zero point energy corrections, while noncompact cyclic structures are preferred when temperature and entropy are accounted for. PMID- 20590082 TI - The fate of H atom adducts to 3'-uridine monophosphate. AB - The stabilities of the adducts deriving from H free radical addition to the O2, O4, and C5 positions of 3'-uridine monophosphate (3'UMP) are studied by the hybrid density functional B3LYP approach. Upon H atom addition at the O2 position, a concerted low-barrier proton-transfer process will initially occur, followed by the potential ruptures of the N-glycosidic or beta-phosphate bonds. The rupture barriers are strongly influenced by the rotational configuration of the phosphate group at the 3' terminal, and are influenced by bulk solvation effects. The O4-H adduct has the highest thermal stability, as the localization of the unpaired electron does not enable cleavage of either the C1'-N1 or the C3' O(P) bonds. For the most stable adduct, with H atom added to the C5 position, the rate-controlled step is the H2'a abstraction by the C6 radical site, after which the subsequent strand rupture reactions proceed with low barriers. The main unpaired electron densities are presented for the transient species. Combined with previous results, it is concluded that the H atom adducts are more facile to drive the strand scission rather than N-glycosidic bond ruptures within the nucleic acid bases. PMID- 20590083 TI - Acetic acid aldol reactions in the presence of trimethylsilyl trifluoromethanesulfonate. AB - In the presence of TMSOTf and a trialkylamine base, acetic acid undergoes aldol addition to non-enolizable aldehydes under exceptionally mild conditions. Acidic workup yields the beta-hydroxy carboxylic acid. The reaction appears to proceed via a three-step, one-pot process, including in situ trimethylsilyl ester formation, bis-silyl ketene acetal formation, and TMSOTf-catalyzed Mukaiyama aldol addition. Independently synthesized TMSOAc also undergoes aldol additions under similar conditions. PMID- 20590084 TI - Self-aligned memristor cross-point arrays fabricated with one nanoimprint lithography step. AB - We demonstrate a technique to fabricate memristor cross-point arrays using a self aligned, one step nanoimprint lithography process that simultaneously patterns the bottom electrode, switching material film and the top electrode. Since this process does not require overlay alignment, the fabrication complexity is greatly reduced and the throughput is significantly increased. The critical interfaces are exposed to much less contamination and thus under better chemical control. With this technique, we fabricated arrays of TiO(2)-based memristive devices (junction area 100 nm by 100 nm) that did not require electrical forming and were operated with nanoampere currents. PMID- 20590085 TI - Mild and highly enantioselective vinylogous aldol reaction of Brassard's diene with aromatic aldehydes by combined Lewis acid catalyst. AB - The combined Lewis acid catalytic system, generated from (R)-1,1'-bi-2-naphthol [(R)-BINOL], Ti(O-i-Pr)(4), H(2)O, and lithium chloride, effectively catalyzed the enantioselective vinylogous aldol reaction of Brassard's diene with aromatic aldehydes affording the (Z)-delta-hydroxyl-alpha,beta-unsaturated esters exclusively in good yields with excellent enantioselectivities (90-99% ee) under mild conditions. A Lewis acid-Lewis acid bifunctional working model was proposed for the catalytic process based on some control experiments. PMID- 20590086 TI - A facile construction of bi- or tricyclic skeletons by nickel-catalyzed stereoselective cyclization of alkynylcycloalkanone. AB - A nickel-catalyzed intramolecular cyclization of alkynylalkanone in the presence of Et(3)SiH using an NHC ligand produced various carbo- and heterocycles in a stereoselective manner. The reaction would proceed via formation of oxanickelacycle followed by sigma-bond metathesis with silane to give a bi- or tricyclic compound. PMID- 20590087 TI - Biomimetic synthesis of polycyclic polyprenylated acylphloroglucinol natural products isolated from Hypericum papuanum. AB - Biomimetic syntheses of three polycylic polyprenylated acylphloroglucinol natural products isolated from Hypericum papuanum, ialibinone A, ialibinone B, and hyperguinone B, have been accomplished by selective oxidative cyclizations of the proposed biosynthetic precursor 5, which was synthesized from phloroglucinol in three steps. PMID- 20590088 TI - Design and synthesis of novel tricyclic benzoxazines as potent 5-HT(1A/B/D) receptor antagonists leading to the discovery of 6-{2-[4-(2-methyl-5-quinolinyl) 1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045). AB - Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT(1A/B/D) receptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in parallel identified 6-{2-[4-(2-methyl-5 quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045) as a potent 5-HT(1A/B/D) receptor antagonist with a high degree of selectivity over human ether-a-go-go related gene (hERG) potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models. On the basis of its outstanding overall profile, this compound was progressed as a clinical candidate with the ultimate aim to assess its potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden. PMID- 20590089 TI - Cu (I)-catalyzed synthesis of polysubstituted pyrroles from dialkyl ethylenedicarboxylates and beta-enamino ketones or esters in the presence of O2. AB - A straightforward method for the synthesis of polysubstituted pyrroles was achieved easily from oxidative cyclization of beta-enamino ketones or esters and alkynoates catalyzed by CuI in the presence of O(2). PMID- 20590090 TI - Molecular simulations reveal the mechanism and the determinants for ampicillin translocation through OmpF. AB - We use a multiscale approach, combining molecular dynamics simulations with metadynamics, to simulate the translocation of ampicillin through OmpF from Escherichia coli (E. coli). In-depth analysis has allowed us to reveal the complete picture of the translocation process in terms of both energetics and physicochemical properties. We have demonstrated the existence of a unique affinity site at the constriction region, accessible from both sides and defined by specific pore-antibiotic interactions. By providing optimal binding, the constriction region works like an enzyme toward the permeation of ampicillin. We find reduction in entropy to be compensated by enthalpic contributions from a favorable network of interactions (hydrogen bonds and hydrophobic contacts) which is also mediated by two slow water molecules bridging the antibiotic-pore interactions. Finally, as ampicillin assumes a preferential value for a torsional angle when at the constriction region, we investigated the consequence of the conformational preorganization of ampicillin toward its translocation. As a whole, our analysis opens the way to chemical modifications of antibiotics to allow improving uptake through porins contributing to combat bacterial resistance. PMID- 20590092 TI - Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. AB - Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, phenols, and coumarins. Polyamines such as spermine, spermidine, and many synthetic congeners are described to constitute a novel class of CA inhibitors (CAIs), interacting with the different CA isozymes with efficiency from the low nanomolar to millimolar range. The main structure-activity relationship for these CAIs have been delineated: the length of the molecule, number of amine moieties, and their functionalization are the main parameters controlling activity. The X-ray crystal structure of the CA II-spermine adduct allowed understanding of the inhibition mechanism. Spermine anchors to the nonprotein zinc ligand through a network of hydrogen bonds. Its distal amine moiety makes hydrogen bonds with residues Thr200 and Pro201, which further stabilize the adduct. Spermine binds differently compared to sulfonamides, phenols, or coumarins, rendering possible to develop CAIs with a diverse inhibition mechanism, profile, and selectivity for various isoforms. PMID- 20590093 TI - Holographically defined nanoparticle placement in 3D colloidal crystals. AB - We demonstrate an optical interference-based photochemical method for the high resolution localization of nanoparticles inside colloidal crystals or other porous structures. The method specifically relies on photoinduced inversion of the colloidal crystal surface charge to drive the localized deposition of charged gold nanoparticles. 4-Bromomethyl-3-nitrobenzoic acid (BNBA) was used as a photocleavable linker, and dansylamide was attached to BNBA to increase the absorption at 351 nm. Two-beam interference lithography was used for high resolution optical patterning of the colloidal crystals; the resulting pattern was then decorated with functional nanoparticles. The periodicity of the pattern was 400 nm, and the width of the gold nanoparticle decorated region was approximately 200 nm. Our strategy of using photoswitching in a refractive-index matched porous medium followed by the attachment of nanoparticles to the photoswitched region should be applicable to wide classes of charged nanoparticles. PMID- 20590095 TI - Total synthesis of enigmazole A from Cinachyrella enigmatica. Bidirectional bond constructions with an ambident 2,4-disubstituted oxazole synthon. AB - The first total synthesis of the cytotoxic marine macrolide enigmazole A has been completed in 22 steps (longest linear sequence). The sensitive, densely functionalized 2,4-disubstituted oxazole fragment was constructed using an efficient Negishi-type coupling of an oxazol-2-ylzinc reagent formed directly from the parent ethyl 2-iodooxazole-4-carboxylate by zinc insertion. Other key steps include a hetero-Diels-Alder cycloaddition to form the central embedded pyran ring, a Wittig reaction to unite Eastern and Western hemispheres, and a ring size-selective Keck macrolactonization. PMID- 20590094 TI - Probing slow protein dynamics by adiabatic R(1rho) and R(2rho) NMR experiments. AB - Slow micros/ms dynamics involved in protein folding, binding, catalysis, and allostery are currently detected using NMR dispersion experiments such as CPMG (Carr-Purcell-Meiboom-Gill) or spin-lock R(1rho). In these methods, protein dynamics are obtained by analyzing relaxation dispersion curves obtained from either changing the time spacing between 180 degree pulses or by changing the effective spin-locking field strength. In this Communication, we introduce a new method to induce a dispersion of relaxation rates. Our approach relies on altering the shape of the adiabatic full passage pulse and is conceptually different from existing approaches. By changing the nature of the adiabatic radiofrequency irradiation, we are able to obtain rotating frame R(1rho) and R(2rho) dispersion curves that are sensitive to slow micros/ms protein dynamics (demonstrated with ubiquitin). The strengths of this method are to (a) extend the dynamic range of the relaxation dispersion analysis, (b) avoid the need for multiple magnetic field strengths to extract dynamic parameters, (c) measure accurate relaxation rates that are independent of frequency offset, and (d) reduce the stress to NMR hardware (e.g., cryoprobes). PMID- 20590097 TI - Clicking fluoroionophores onto mesoporous silicas: a universal strategy toward efficient fluorescent surface sensors for metal ions. AB - Mesoporous SBA-15 silica is an excellent support for constructing fluorescent surface sensors. In this letter, we reported a two-step surface reaction involved strategy to construct efficient fluorescent surface sensors for metal ions by clicking fluoroionophores onto azide-functionalized SBA-15. Our experimental results indicate that such a strategy exhibits an obviously higher loading efficiency within commercial SBA-15 than a previously reported strategy. As a proof-of-concept, a newly designed alkyne-functionalized Hg(2+) fluoroionophore was grafted onto SBA-15 to form a fluorescent Hg(2+) surface sensor. It shows improved sensitivity and selectivity than the fluoroionophore itself working in the solution phase with a detection limit of 2.0 x 10(-8) M for Hg(2+). PMID- 20590096 TI - Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica. AB - Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18 membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 microM. PMID- 20590098 TI - Attractant and repellent signaling conformers of sensory rhodopsin-transducer complexes. AB - Attractant and repellent signaling conformers of the dual-signaling phototaxis receptor sensory rhodopsin I and its transducer subunit (SRI-HtrI) have recently been distinguished experimentally by the opposite connection of their retinylidene protonated Schiff bases to the outwardly located periplasmic side and inwardly located cytoplasmic side. Here we show that the pK(a) of the outwardly located Asp76 counterion in the outwardly connected conformer is lowered by approximately 1.5 units from that of the inwardly connected conformer. The pK(a) difference enables quantitative determination of the relative amounts of the two conformers in wild-type cells and behavioral mutants prior to photoexcitation, comparison of their absorption spectra, and determination of their relative signaling efficiency. We have shown that the one-photon excitation of the SRI-HtrI attractant conformer causes a Schiff base connectivity switch from inwardly connected to outwardly connected states in the attractant signaling photoreaction. Conversely, a second near-UV photon drives the complex back to the inwardly connected conformer in the repellent signaling photoreaction. The results suggest a model of the color-discriminating dual-signaling mechanism in which phototaxis responses (his-kinase modulation) result from the photointerconversion of the two oppositely connected SRI-HtrI conformers by one photon and two-photon activation. Furthermore, we find that the related repellent phototaxis SRII-HtrII receptor complex has an outwardly connected retinylidene Schiff base like the repellent signaling forms of the SRI-HtrI complex, indicating the general applicability of macro conformational changes, which can be detected by the connectivity switch, to phototaxis signaling by sensory rhodopsin-transducer complexes. PMID- 20590099 TI - Localizable and highly sensitive calcium indicator based on a BODIPY fluorophore. AB - We introduce here a new class of BODIPY-based Ca2+ indicators which can be derivatized with biological ligands that permit the localization of the indicators in living cells. The underivatized BODIPY-based Ca2+ indicator (BOCA 1) shows a 250-fold increase in fluorescence intensity upon Ca2+ binding. We also prepared its O6-benzylguanine (BG) derivative, BOCA-1-BG, which can be covalently and specifically linked to SNAP-tag fusion proteins in living cells. The indicator retains its properties as a highly sensitive Ca2+ indicator after conjugation to proteins, displaying a 180-fold increase in fluorescence intensity upon Ca2+ binding. We further demonstrated that BOCA-1-BG through reaction with localized SNAP-tag fusion proteins can be used to sense changes in Ca2+ concentrations in the nuclei and in the cytosol of live CHO-K1 cells. The high sensitivity of the indicator together with the possibility to selectively couple it to proteins of interest makes it a powerful tool for measuring local changes in Ca2+ concentrations in living cells. PMID- 20590100 TI - Cellular localization of clathridimine, an antimicrobial 2-aminoimidazole alkaloid produced by the Mediterranean calcareous sponge Clathrina clathrus. AB - Chemical investigation of the Mediterranean calcareous sponge Clathrina clathrus led to the isolation of large amounts of a new 2-aminoimidazole alkaloid, named clathridimine (1), along with the known clathridine (2) and its zinc complex (3). The structure of the new metabolite was assigned by detailed spectroscopic analysis. Clathridimine (1) displayed selective anti-Escherichia coli and anti Candida albicans activities. Clathridine (2) showed only anti-Candida albicans activity, and its zinc complex (3) exhibited selective anti-Staphylococcus aureus activity. The isolation of analogues of 2-amino-imidazole derivatives from several Leucetta species from various sites in the Pacific Ocean and the Red Sea raises the question of their biosynthetic origin. Microscopic studies revealed abundant extracellular bacteria located in the mesohyl of the sponge, with two predominant morphotypes including spiral bacteria and long, narrow bacilli. Chemical analysis with HPLC/UV/ELSD profiles of sponge cells separated from bacteria by differential centrifugation and trypsinization of the sponge cell surface revealed that clathridine (2) was localized in the sponge cells. PMID- 20590101 TI - Short access to 6-substituted pyrimidine derivatives by the S(RN)1 mechanism. Synthesis of 6-substituted uracils through a one-pot procedure. AB - The synthesis of 6-substituted 2,4-dimethoxypyrimidines with different nucleophiles was accomplished with good to excellent yields (50-95%) through S(RN)1 reactions, starting from commercially available 6-chloro-2,4 dimethoxypyrimidine (1). Hydrolysis of these derivatives gave access to 6 substituted uracils with good yields and short times by the use of microwave irradiation. The preparation of uracils from 1 without the isolation of 2,4 dimethoxypyrimidine derivatives affords a rapid access to these compounds in good yields and excellent purity by avoiding an unnecessary step of purification. PMID- 20590102 TI - The rotational structure of the origin band of the pulsed-field-ionization, zero kinetic-energy photoelectron spectra of propene-h(6) and propene-d(6). AB - The pulsed-field-ionization zero-kinetic-energy photoelectron spectra of the origin band of the + 2A'' <- 1A' transition of propene (C3H6) and perdeuterated propene (C3D6) have been recorded at high resolution, allowing for the partial resolution of the rotational structure. The analysis of the spectra in the realm of the orbital ionization model for rigid-rotor asymmetric-top molecules enabled the determination of the adiabatic ionization energy of propene and the rotational constants of C3H6+ and C3D6+. The tunneling splittings resulting from the hindered rotation of the methyl group could not be resolved, and the analysis was therefore carried out in the Cs molecular symmetry group. Angular momentum contributions of ppi, dpi, and ddelta character were included in the single center expansion describing the molecular orbital out of which ionization occurs, leading to the selection rules |DeltaN| = |N+ - N''| <= 2 and DeltaKa = Ka+ - Ka'' = +/-1, +/-2 and to photoelectron partial waves with angular momentum quantum number up to l = 3. The observation of a strong spectral feature associated with DeltaKa = 0 indicates the importance of vibronic interactions. PMID- 20590103 TI - Designable biointerfaces using vapor-based reactive polymers. AB - Functionalized poly(p-xylylenes) constitute a versatile class of reactive polymers that can be prepared in a solventless process via chemical vapor deposition (CVD) polymerization. The resulting ultrathin coatings are typically pinhole-free and can be conformally deposited onto a wide range of substrates and materials. More importantly, appropriately selected functional groups can serve as anchoring sites for tailoring biointerface properties via the immobilization of biomolecules. In this article, controlled surface chemistries are outlined that use functionalized poly(p-xylylenes) as reactive coatings, including alkyne functionalized coatings for Huisgen 1,3-dipolar cycloaddition reactions or aldehyde-functionalized coatings. The reactive coatings technology provides flexible access to a range of different surface chemistries, enabling a broad range of potential applications in microfluidics, medical device coatings, and biotechnology. In this feature article, we will highlight recent progress in vapor-based reactive coatings and will discuss potential benefits and current limitations. PMID- 20590104 TI - A general palladium catalyst system for Suzuki-Miyaura coupling of potassium aryltrifluoroborates and aryl mesylates. AB - The first general examples of palladium-catalyzed Suzuki-type cross-coupling of aryl and heteroaryl mesylates with potassium aryl and heteroaryltrifluoroborates are presented. In addition to biaryl couplings, the cross-coupling reactions of aryl mesylates with alkyl and vinyltrifluoroborate salts have also been successfully accomplished. PMID- 20590105 TI - Copper-catalyzed sequential alkyl/aryl or vinyl esterification of dicarboxylic acid anhydrides with alkoxysilanes. AB - A copper(I)-catalyzed bis-esterification of cyclic anhydrides with aryl and vinyl alkoxysilanes is described, in which the alkoxy and aryl (or vinyl) esters of dicarboxylic acids were prepared in one pot with moderate to good yields. Notably, vinyl trimethoxysilanes also worked well with this procedure. PMID- 20590106 TI - Colorimetric and ratiometric red fluorescent chemosensor for fluoride ion based on diketopyrrolopyrrole. AB - Three new diketopyrrolopyrrole (DPP) compounds are shown to be colorimetric and ratiometric red fluorescent sensors for fluoride anions with high sensitivity and selectivity. The recognition mechanism is attributed to the intermolecular proton transfer between a hydrogen atom on the lactam N positions of the DPP moiety and the fluoride anion. PMID- 20590107 TI - Synthesis, cell-surface binding, and cellular uptake of fluorescently labeled glucose-DNA conjugates with different carbohydrate presentation. AB - Oligonucleotide conjugates carrying carbohydrates at the 5'-end have been prepared. Glucose, fucose, and saccharides containing glucose at the nonreducing end were attached to DNA strands using the classical phosphoramidite chemistry. Two types of spacers and a dendron scaffold helped to obtain a diversity of sugar presentations in the DNA conjugates. Cellular surface adsorption and cellular uptake of carbohydrate oligonucleotide antisense sequences were measured using flow cytometric analysis. Conjugates with the glucose moiety linked through long spacers (15 to 18 atom distances) were internalized better than those with short linkers (4 atom distance) and than DNA control strands without sugar modification. Conjugates with tetravalent presentation of glucose did not improve cell uptake. PMID- 20590108 TI - Nanoparticle dissolution from the particle perspective: insights from particle sizing measurements. AB - In this study, the dissolution of copper nanoparticles in aqueous low-pH suspensions is examined. The dissolution phenomenon is examined using both bulk measurements of copper ion production, as detected by inductively coupled plasma optical emission spectroscopy (ICP/OES), and a decrease in nanoparticle size using particle-sizing instruments. For size measurements, an electrospray atomizer coupled to a scanning mobility particle sizer (ES-SMPS) was used to monitor changes in the particle size distribution (PSD) of the copper nanoparticles as they dissolved in hydrochloric acid solution in real time. Measured PSDs show interesting changes during the dissolution process, including a change in modality (mono to multi) with time. Although there may be several causes for the observed modality changes upon dissolution, it is clear that only through direct measurements of nanoparticles and nanoparticle PSDs can these dynamic details be captured as these particles change size, thus providing important insights into nanoscale processes. PMID- 20590109 TI - Combining host-guest systems with nonfouling material for the fabrication of a biosurface: toward nearly complete and reversible resistance of cytochrome c. AB - In this letter, a pH-responsive reactivated biointerface is fabricated using an inclusion reaction between an azobenzene-containing self-assembled monolayer and pH-responsive poly(ethylene glycol)-block-poly(acrylic acid) grafted with cyclodextrins. The pH-responsive interface can be switched between an extended state and a relaxed state for the reversible resistance of cytochrome c adsorption completely in cooperation with protein-resistant poly(ethylene glycol). PMID- 20590110 TI - Bayesian maximum entropy integration of ozone observations and model predictions: an application for attainment demonstration in North Carolina. AB - States in the USA are required to demonstrate future compliance of criteria air pollutant standards by using both air quality monitors and model outputs. In the case of ozone, the demonstration tests aim at relying heavily on measured values, due to their perceived objectivity and enforceable quality. Weight given to numerical models is diminished by integrating them in the calculations only in a relative sense. For unmonitored locations, the EPA has suggested the use of a spatial interpolation technique to assign current values. We demonstrate that this approach may lead to erroneous assignments of nonattainment and may make it difficult for States to establish future compliance. We propose a method that combines different sources of information to map air pollution, using the Bayesian Maximum Entropy (BME) Framework. The approach gives precedence to measured values and integrates modeled data as a function of model performance. We demonstrate this approach in North Carolina, using the State's ozone monitoring network in combination with outputs from the Multiscale Air Quality Simulation Platform (MAQSIP) modeling system. We show that the BME data integration approach, compared to a spatial interpolation of measured data, improves the accuracy and the precision of ozone estimations across the state. PMID- 20590111 TI - Acid-base behavior of the gaspeite (NiCO3(s)) surface in NaCl solutions. AB - Gaspeite is a low reactivity, rhombohedral carbonate mineral and a suitable surrogate to investigate the surface properties of other more ubiquitous carbonate minerals, such as calcite, in aqueous solutions. In this study, the acid-base properties of the gaspeite surface were investigated over a pH range of 5 to 10 in NaCl solutions (0.001, 0.01, and 0.1 M) at near ambient conditions (25 +/- 3 degrees C and 1 atm) by means of conventional acidimetric and alkalimetric titration techniques and microelectrophoresis. Over the entire experimental pH range, surface protonation and electrokinetic mobility are strongly affected by the background electrolyte, leading to a significant decrease of the pH of zero net proton charge (PZNPC) and the pH of isoelectric point (pH(iep)) at increasing NaCl concentrations. This challenges the conventional idea that carbonate mineral surfaces are chemically inert to background electrolyte ions. Multiple sets of surface complexation reactions (i.e., ionization and ion adsorption) were formulated within the framework of three electrostatic models (CCM, BSM, and TLM) and their ability to simulate proton adsorption and electrokinetic data was evaluated. A one-site, 3-pK, constant capacitance surface complexation model (SCM) reproduces the proton adsorption data at all ionic strengths and qualitatively predicts the electrokinetic behavior of gaspeite suspensions. Nevertheless, the strong ionic strength dependence exhibited by the optimized SCM parameters reveals that the influence of the background electrolyte on the surface reactivity of gaspeite is not fully accounted for by conventional electrostatic and surface complexation models and suggests that future refinements to the underlying theories are warranted. PMID- 20590112 TI - Anthraquinone-based discotic liquid crystals. AB - The syntheses of six room-temperature discotic liquid crystals based on an alkoxy anthraquinone (AQ) framework is described. Differential scanning calorimetry, X ray diffraction (XRD), and cross-polarized microscopy were used to identify phases and confirm phase-transition temperatures. Cross-polarized microscopy results suggest columnar discotic structures at room temperature. However, the AQ derivatives also undergo mesophase-to-mesophase transitions, which are attributed to rectangular- to hexagonal-columnar discotic transitions based on XRD analysis. Furthermore, some of the compounds display remarkable liquid crystalline phase stability that spans from -50 to 150 degrees C, a useful temperature range for organic materials applications. The different AQ derivatives did not exhibit electronic perturbations, as all compounds have absorption onsets of approximately 400 nm. Finally, solution cyclic voltammetry of the AQ derivatives was carried out to determine the redox potentials, diffusion coefficients, and electron transfer rate constants. All AQ derivatives had E(1/2) values that ranged between -1.52 and -1.70 V vs Fc/Fc(+). Diffusion coefficients and electron transfer rates for all AQ derivatives ranged between 0.4 and 7.1 x 10(-6) cm(2) x s(-1) and 0.9 and 5.2 x 10(-3) cm x s(-1), respectively. PMID- 20590113 TI - Hydrogels with cylindrically symmetric structure at macroscopic scale by self assembly of semi-rigid polyion complex. AB - A hydrogel with cylindrically symmetric structure at macroscopic scale has been developed by polymerization of a cationic monomer in the presence of a small amount of semi-rigid polyanion poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) in a cylinder glass tube. The polyion complex radially aligns in the outer region of the synthesized cylinder gel. On the other hand, it orients in concentric and axial directions in the inner region. To the authors' knowledge, this is the first report of such millimeter-scale ordered structure developed in a polymeric hydrogel. We elucidate that homeotropic alignment on the glass wall is energetically favorable for the semi-rigid polyion complex, resulting in the radial orientation in the outer region. In the inner region, the oriented structures result from the monomer difffusion (due to the heterogeneous polymerization) that induces PBDT orientation perpendicular to the diffusion direction. The structured gels showing sensitive response of birefringence to external force are expected to find applications in optical sensors. PMID- 20590114 TI - Thionate versus Oxon: comparison of stability, uptake, and cell toxicity of ((14)CH(3)O)(2)-labeled methyl parathion and methyl paraoxon with SH-SY5Y cells. AB - The stability, hydrolysis, and uptake of the organophosphates methyl parathion and methyl paraoxon were investigated in SH-SY5Y cells. The stabilities of ((14)CH(3)O)(2)-methyl parathion ((14)C-MPS) and ((14)CH(3)O)(2)-methyl paraoxon ((14)C-MPO) at 1 microM in culture media had similar half-lives of 91.7 and 101.9 h, respectively. However, 100 microM MPO caused >95% cytotoxicity at 24 h, whereas 100 microM MPS caused 4-5% cytotoxicity at 24 h ( approximately 60% cytotoxicity at 48 h). Greater radioactivity was detected inside cells treated with MPO as compared to MPS, although >80% of the total MPO uptake was primarily dimethyl phosphate (DMP). Maximum uptake was reached after 48 h of (14)C-MPS or (14)C-MPO exposure with total uptakes of 1.19 and 1.76 nM/10(6) cells for MPS and MPO, respectively. The amounts of MPS and MPO detected in the cytosol after 48 h of exposure time were 0.54 and 0.37 nM/10(6) cells, respectively. PMID- 20590115 TI - Identification of disulfide bonds in protein proteolytic degradation products using de novo-protein unique sequence tags approach. AB - Disulfide bonds are a form of post-translational modification that often determines protein structure(s) and function(s). In this work, we report a mass spectrometry method for identification of disulfides in degradation products of proteins, specifically endogenous peptides in the human blood plasma peptidome. LC-Fourier transform tandem mass spectrometry (FT MS/MS) was used for acquiring mass spectra that were de novo sequenced and then searched against the IPI human protein database. Through the use of unique sequence tags (UStags), we unambiguously correlated the spectra to specific database proteins. Examination of the UStags' prefix and/or suffix sequences that contain cysteine(s) in conjunction with sequences of the UStags-specified database proteins is shown to enable the unambigious determination of disulfide bonds. Using this method, we identified the intermolecular and intramolecular disulfides in human blood plasma peptidome peptides that have molecular weights of up to approximately 10 kDa. PMID- 20590116 TI - Flexibility of shape-persistent molecular building blocks composed of p-phenylene and ethynylene units. AB - Ethynylene and p-phenylene are frequently employed constitutional units in constructing the backbone of nanoscopic molecules with specific shape and mechanical or electronic function. How well these properties are defined depends on the flexibility of the backbone, which can be characterized via the end-to-end distance distribution. This distribution is accessible by pulse electron paramagnetic resonance (EPR) distance measurements between spin labels that are attached at the backbone. Four sets of oligomers with different sequences of p phenylene and ethynylene units and different spin labels were prepared using polar tagging as a tool for simple isolation of the targeted compounds. By variation of backbone length, of the sequence of p-phenylene and ethynylene units, and of the spin labels a consistent coarse-grained model for backbone flexibility of oligo(p-phenyleneethynylene)s and oligo(p-phenylenebutadiynylene)s is obtained. The relation of this harmonic segmented chain model to the worm-like chain model for shape-persistent polymers and to atomistic molecular dynamics simulations is discussed. Oligo(p-phenylenebutadiynylene)s are found to be more flexible than oligo(p-phenyleneethynylene)s, but only slightly so. The end-to-end distance distribution measured in a glassy state of the solvent at a temperature of 50 K is found to depend on the glass transition temperature of the solvent. In the range between 91 and 373 K this dependence is in quantitative agreement with expectations for flexibility due to harmonic bending. For the persistence lengths at 298 K our data predict values of (13.8 +/- 1.5) nm for poly(p phenyleneethynylene)s and of (11.8 +/- 1.5) nm for poly(p phenylenebutadiynylene)s. PMID- 20590117 TI - Simultaneous noncontact topography and electrochemical imaging by SECM/SICM featuring ion current feedback regulation. AB - We described a hybrid system of scanning electrochemical microscopy (SECM) and scanning ion conductance microscopy (SICM) with ion current feedback nanopositioning control for simultaneous imaging of noncontact topography and spatial distribution of electrochemical species. A nanopipette/nanoring electrode probe provided submicrometer resolution of the electrochemical measurement on surfaces with complex topology. The SECM/SICM probe had an aperture radius of 220 nm. The inner and outer radii of the SECM Au nanoring electrode were 330 and 550 nm, respectively. Characterization of the probe was performed with scanning electron microscopy (SEM), cyclic voltammetry (CV), and approach curve measurements. SECM/SICM was applied to simultaneous imaging of topography and electrochemical responses of enzymes (horse radish peroxidase (HRP) and glucose oxidase (GOD)) and single live cells (A6 cells, superior cervical ganglion (SCG) cells, and cardiac myocytes). The measurements revealed the distribution of activity of the enzyme spots on uneven surfaces with submicrometer resolution. SECM/SICM acquired high resolution topographic images of cells together with the map of electrochemical signals. This combined technique was also applied to the evaluation of the permeation property of electroactive species through cellular membranes. PMID- 20590119 TI - Infrared spectroscopy reveals the nonsynchronicity phenomenon in the glassy to fluid micellar transition of DSPE-PEG2000 aqueous dispersions. AB - One challenging question regarding the phase transition mechanism of amphiphiles is to seek the roles individual groups/portions of the amphiphilic molecule play during the transformation. To address this question, we selected a poly(ethylene glycol)-grafted phospholipid, distearoylphosphatidylethanolamine-N [methoxy(poly(ethylene glycol))-2000] (DSPE-PEG2000), to study its glassy to fluid micellar phase transition by using differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopy. FTIR results revealed that during the glassy to fluid micellar transition, the lipid acyl tails have evident conformational rearrangements but undergo only slight modifications in the packing state. For the lipid interface region, small changes in the hydration state of C=O groups were observed, whereas for the lipid headgroups (NHCO and PO(4)(-)), their conformation and hydration states remain unchanged. Thus, the head, the interface, and the tail regions of DSPE-PEG2000 molecules change nonsynchronously during the transition. As to the bulky PEG corona residing at the outer micellar surface, no evident hydration state change was observed upon heating, and its behavior is almost the same as that of the hydrated free PEG2000 molecules. Such a nonsynchronous change in different parts of the self-assembled amphiphilic aggregates undergoing phase transition could be a common phenomenon that needs to be widely recognized. PMID- 20590120 TI - Cutting of oxidized graphene into nanosized pieces. AB - We report a simple approach to producing nanosized graphene on the basis of chemical oxidation of a graphene sheet followed by cutting of the sheet using a scanning probe microscopic (SPM) manipulation technique. The structural and electronic properties of the oxidized sheet are characterized by noncontact atomic force microscopic (NC-AFM) imaging and SPM spectroscopy under ultrahigh vacuum conditions. Regularly spaced linear defects with a spacing of 5-10 nm and a length of >100 nm were found on the sheet, which can be attributed to the result of linear arrangement of epoxide functional groups. The cutting experiments are performed on sheets in which the linear defects were observed in advance. Cutting is initiated by a point contact between the preoxidized sheet and the AFM probe. The local mechanical stress caused by the point contact leads to rupture of the sheet, which proceeds linearly along the linear defect of the epoxide groups. We propose that the linear defect structures can be used as a template to determine the cutting direction of the sheet. According to recently proposed theoretical predictions, the linear epoxide groups have preferential alignment along a zigzag direction in the graphene lattice, and therefore, the cut edge shape could have well-defined alignment along the zigzag direction. This cutting procedure of the graphene sheet could be a useful method for the production of nanosized graphene with well-defined edges. PMID- 20590121 TI - Tracking giant folds in a monolayer. AB - The collapse dynamics of giant folds in a catanionic monolayer at the air-water interface are examined. A monolayer of dioctadecyldimethylammonium bromide (DODAB) and sodium dodecyl sulfate (SDS) in a 1:1 ratio is the system of study that previously was found to fold upon compression in a Langmuir trough. Carboxylate-coated polystyrene beads (1 microm diameter) are deposited and bound to the monolayer. Displacement of the beads is measured with epifluorescence microscopy and particle image velocimetry, yielding a measurement of the velocity of the monolayer around the fold. Reversibility is confirmed by measuring the amount of monolayer material entering and leaving the fold. Material near folds are found to have a maximum relative velocity on the order of 0.1 mm/s, and fold depths are found to be on the order of 1 mm. The folds exhibit regular unfolding behavior, which can be explained qualitatively by a simple mechanical model. PMID- 20590122 TI - Guided deposition of individual DNA nanostructures on silicon substrates. AB - We demonstrate immobilization of DNA nanostructures (37 nm x 8 nm) on silicon by a combination of "top-down" fabrication and "bottom-up" self-assembly. Anchor lines and pads were defined using electron beam lithography and a cationic molecular monolayer. Individual DNA nanostructures bind in 85% yield onto the anchor pads and can be washed and imaged in air. The strength of the binding interaction between a DNA nanostructure and its anchor pad is at least -43 kJ/mol. PMID- 20590123 TI - Thermal modulation voltammetry at a 1,2-dichloroethane/water microinterface using visible laser heating with optically absorbing supporting electrolyte. AB - Thermal modulation voltammetry (TMV) using laser heating at a liquid/liquid microinterface is a useful technique for determining the standard entropy change of ion transfer. In this work, for achieving TMV using a visible laser as a heating source at a 1,2-dichloroethane (DCE)/water microinterface, we used an optically absorbing supporting electrolyte, i.e., crystalviolet tetrakis(4 chlorophenyl)borate (CVTClPB). CVTClPB served well not only as a supporting electrolyte but also as an optical absorber in the DCE solution, and thereby, well-defined linear sweep (LS) and TM voltammograms could be obtained. On the basis of LS and thermal modulation (TM) voltammograms obtained with CVTClPB, the standard entropy changes of ion transfer for six model ions were successfully determined. PMID- 20590125 TI - Nanomorphology of bulk heterojunction photovoltaic thin films probed with resonant soft X-ray scattering. AB - The bulk nanomorphology of organic bulk heterojunction devices, particularly of all-polymer devices, is difficult to characterize due to limited electron density contrast between constituent materials. Resonant soft X-ray scattering can overcome this problem and is used to show that the morphologies in chloroform cast and subsequently annealed polyfluorene copolymer poly(9,9'-dioctylfluorene co-bis(N,N'-(4,butylphenyl))bis(N,N'-phenyl-1,4-phenylene)diamine) (PFB) and poly(9,9'-dioctylfluorene-co-benzothiadiazole) (F8BT) blends exhibit a hierarchy of length scales with impure domains in as-cast films. With annealing, these domains first become purer at the smallest length scale and only then evolve in size with annealing. Even optimized cells using present fabrication methods are found to have a dominant domain size much larger than the exciton diffusion length. The observed morphology is far from ideal for efficient solar cell operation and very different from those achieved in high-efficiency fullerene based devices. This strongly implies that lack of morphological control contributes to the relatively poor performance of the all-polymer PFB/F8BT devices and may be problematic for all-polymer devices in general. Novel processing strategies will have to be employed to harness the full potential these high open circuit voltage devices offer. PMID- 20590124 TI - Interplay of permanent charge and hydrophobicity in the electrospray ionization of glycans. AB - The analysis of N-linked glycans by mass spectrometry (MS) has been characterized by low signal-to-noise ratios and high limits of detection due to their hydrophilicity and lack of basic sites able to be protonated. As a result, every step in glycan sample preparation must be thoroughly optimized in order to minimize sample loss, contamination, and analytical variability. Importantly, properties of glycans and their derivatized counterparts must be thoroughly studied in order to exploit certain characteristics for enhancing MS analysis. Herein, the effectiveness of the incorporation of a permanent charge is studied and determined to hamper glycan analysis. Also, a procedure for glycan hydrazone formation is optimized and outlined where a large number of variables were simultaneously analyzed using a fractional factorial design (FFD) in order to determine which conditions affected the reaction efficiency of the hydrazone formation reaction. Finally, the hydrophobic tagging of glycans is shown to be a viable opportunity to further increase the ion abundance of glycans in MS. PMID- 20590127 TI - Ion transport in nanofluidic funnels. AB - We report fabrication of nanofluidic channels with asymmetric features (e.g., funnels) that were cast in high modulus poly(dimethylsiloxane) and had well defined geometries and dimensions. Masters used to cast the funnels were written in the negative tone resist SU-8 by electron beam lithography. Replicated funnels had taper angles of 5, 10, and 20 degrees and were 80 nm wide at the tip, 1 microm wide at the base, and 120 nm deep. The planar format permitted easy coupling of the funnels to microfluidic channels and simultaneous electrical and optical characterization of ion transport. All three designs rectified ion current, and the 5 degrees funnel exhibited the highest rectification ratio. Fluorescence measurements at the funnel base showed that an anionic probe was enriched and depleted in the high and low conductance states, respectively. PMID- 20590128 TI - Redox exchange induced MnO2 nanoparticle enrichment in poly(3,4 ethylenedioxythiophene) nanowires for electrochemical energy storage. AB - MnO2 nanoparticle enriched poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires are fabricated by simply soaking the PEDOT nanowires in potassium permanganate (KMnO4) solution. The structures of these MnO2 nanoparticle enriched PEDOT nanowires are characterized by SEM and TEM, which show that the MnO2 nanoparticles have uniform sizes and are finely dispersed in the PEDOT matrix. The chemical constituents and bonding of these composite nanowires are characterized by energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, and infrared spectroscopy, which indicate that the formation and dispersion of these MnO2 nanoparticles into the nanoscale pores of the PEDOT nanowires are most likely triggered by the reduction of KMnO4 via the redox exchange of permanganate ions with the functional group on PEDOT. Varying the concentrations of KMnO4 and the reaction time controls the loading amount and size of the MnO2 nanoparticles. Cyclic voltammetry and galvanostatic charge discharge are used to characterize the electrochemical properties of these MnO2 nanoparticle loaded PEDOT nanowires. Due to their extremely high exposed surface area with nanosizes, the pristine MnO2 nanoparticles in these MnO2 nanoparticle enriched PEDOT nanowires show very high specific capacitance (410 F/g) as the supercapacitor electrode materials as well as high Li+ storage capacity (300 mAh/g) as cathode materials of Li ion battery, which boost the energy storage capacity of PEDOT nanowires to 4 times without causing excessive volume expansion in the polymer. The highly conductive and porous PEDOT matrix facilitates fast charge/discharge of the MnO2 nanoparticles and prevents them from agglomerating. These synergic properties enable the MnO2 nanoparticle enriched PEDOT nanowires to be promising electrode materials for supercapacitors and lithium ion batteries. PMID- 20590129 TI - Colloidal PbS quantum dot solar cells with high fill factor. AB - We fabricate PbS colloidal quantum dot (QD)-based solar cells using a fullerene derivative as the electron-transporting layer (ETL). A thiol treatment and oxidation process are used to modify the morphology and electronic structure of the QD films, resulting in devices that exhibit a fill factor (FF) as high as 62%. We also show that, for QDs with a band gap of less than 1 eV, an open circuit voltage (VOC) of 0.47 V can be achieved. The power conversion efficiency reaches 1.3% under 1 sun AM1.5 test conditions and 2.4% under monochromatic infrared (lambda=1310 nm) illumination. A consistent mechanism for device operation is developed through a circuit model and experimental measurements, shedding light on new approaches for optimization of solar cell performance by modifying the interface between the QDs and the neighboring charge transport layers. PMID- 20590130 TI - Snake venomics of Bothriechis nigroviridis reveals extreme variability among palm pitviper venoms: different evolutionary solutions for the same trophic purpose. AB - We report the proteomic characterization and biological activities of the venom of the black-speckled palm pitviper, Bothriechis nigroviridis, a neotropical arboreal pitviper from Costa Rica. In marked contrast to other Bothriechis species investigated, the venom of B. nigroviridis does not possess detectable Zn(2+)-dependent metalloproteinases, and is uniquely characterized by a high content of crotoxin-like PLA(2) and vasoactive peptides. These data suggest that different evolutionary solutions have evolved within the arboreal genus Bothriechis for the same trophic purpose. The venom from B. nigroviridis is devoid of hemorrhagic activity, has low edematogenic and coagulant effects, presents modest myotoxic and phospholipase A(2) activities, but has higher lethality than the venoms of other Bothriechis species. Neutralization of its lethal activity by an anti-Crotalus durissus terrificus antivenom confirmed the major role of crotoxin-like PLA(2) in B. nigroviridis venom-induced lethality. PMID- 20590131 TI - Iron-catalyzed domino process for the synthesis of alpha-carbonyl furan derivatives via one-pot cyclization reaction. AB - The Fe(ClO(4))(3)-catalyzed intramolecular rearrangement/cyclization/oxidation reaction sequence for the synthesis of alpha-carbonyl furan derivatives from electron-deficient alkynes and 2-yn-1-ols is reported. PMID- 20590132 TI - Using hydrogel microparticles to transfer hydrophilic nanoparticles and enzymes to organic media via stepwise solvent exchange. AB - We present a simple and versatile approach of using hydrogel microparticles to transfer both inorganic hydrophilic nanoparticles (NPs) such as CdTe quantum dots and enzymes such as lipase B from Candida antarctica (CalB) to organic media and eventually encapsulate them in the gel microparticles by consecutive exchange of the water swollen in the hydrogel microparticles with water-miscible organic solvents and water-immiscible solvents. The entrapment of hydrophilic nanoparticles is due to their incompatibility with water-immiscible organic solvents soaked in the gel matrices and in the surrounding environment, so the present approach obviates the need for any chemical modification to the NP surface or to the hydrogel and furthermore does not require any size matching or chemical affinity of the NPs for the hydrogel networks. The solvent exchange process causes little change of the intrinsic properties of hydrophilic nanoparticles; CdTe quantum dots encapsulated in hydrogel microparticles, dispersed in water-immiscible organic solvents, remain strongly fluorescent, and CalB retains high catalytic activity. Of importance is that the hydrophilic nanoparticles encapsulated in the gel microparticles in organic media can be completely recovered in aqueous media via reversed solvent exchange. As a consequence, the present approach should hold immense promise for technical applications, especially in catalysis. PMID- 20590133 TI - Double-layer formation of [Bmim][PF6] ionic liquid triggered by surface negative charge. AB - Applications of ionic liquids (ILs) in electrified interfaces and electrochemical systems require insight into the molecular-level structure and properties of the interfacial ILs. Using atomistic molecular dynamics (MD) simulations, we show here that a new double-layer stacking formation of the [Bmim][PF(6)] IL can be triggered by the surface negative charge. We also found that the double-layer formation induced by the surface charge thoroughly extended into the bulk phase, implying a strong unscreened ion effect in our IL system. Further study indicated that the double-layer formation in the bulk phase was due to a rapid structural transition. Different IL formations, including the conventional adsorption layer and the double-layer formation, can be achieved in sequence by increasing the surface negative charge. Moreover, the diffusion ability of the new double-layer formation in the bulk phase is much lower when compared to that observed in its original uncharged condition. The structure and properties of the ILs formation may be attributed to the tail-tail aggregation hypothesis of the nonpolar domain in the IL. PMID- 20590134 TI - The V510D suppressor mutation stabilizes DeltaF508-CFTR at the cell surface. AB - Deletion of Phe508 (DeltaF508) in the first nucleotide-binding domain (NBD1) of CFTR causes cystic fibrosis. The mutation severely reduces the stability and folding of the protein by disrupting interactions between NBD1 and the second transmembrane domain (TMD2). We found that replacement of Val510 with acidic residues (but not neutral or positive residues) promoted maturation of DeltaF508 CFTR with V510D more efficiently than V510E. Promotion of DeltaF508-CFTR maturation did not require NBD2 as introduction of V510D into a DeltaNBD2/DeltaF508-CFTR mutant restored maturation to levels similar to that of full-length protein. The V510D mutation increased the half-life of mature DeltaF508-CFTR at the cell surface by about 5-fold to resemble the half-life of wild-type CFTR. It was also observed that introduction of the V510R/R1070D mutations into DeltaF508-CFTR also promoted maturation whereas the V510D/R1070A mutations did not. We propose that the V510D mutation in NBD1 promotes maturation and stabilizes DeltaF508-CFTR at the cell surface through formation of a salt bridge with Arg1070 in TMD2. PMID- 20590135 TI - Initial colloid deposition on bare and zeolite-coated stainless steel and aluminum: influence of surface roughness. AB - The impact of surface roughness of bare and zeolite ZSM-5 coated stainless steel and aluminum alloy on colloid deposition has been investigated using a parallel plate flow chamber system in an aqueous environment. The metals were systematically polished to alter the surface roughness from nanoscale to microscale, with the subsequent surface roughness of both the bare and coated surfaces varying from 11.2 to 706 nm. The stainless steel and aluminum alloy surfaces are extensively characterized, both as bare and as coated surfaces. Experimental results suggest that ZSM-5 coating and surface roughness have a pronounced impact on the kinetics of the colloid deposition. The ZSM-5 coating reduced colloid adhesion compared to the corresponding bare metal surface. In general, the greater surface roughness of like samples resulted in higher colloid deposition. Primarily, this is due to greater surface roughness inducing less reduction in the attractive interactions occurring between colloids and collector surfaces. This effect was sensitive to ionic strength and was found to be more pronounced at lower ionic strength conditions. For the most electrostatically unfavorable scenario (ZSM-5 coatings in 1 mM KNO(3)), the enhanced deposition may also be attributed to inherent surface charge heterogeneity of ZSM-5 coatings due to aluminum in the crystalline structure. The two exceptions are ZSM-5 coated mirror-polished stainless steel and the unpolished aluminum surfaces, which are rougher than the other two samples of the same metal type but result in the least deposition. The reasons for these observations are discussed, as well as the effect of surface charge and hydrophobicity on the adhesion. The relative importance of surface roughness versus contributions of electrostatic interactions and hydrophobicity to the colloid deposition is also discussed. PMID- 20590136 TI - Asymmetric direct vinylogous aldol reaction of unactivated gamma-butenolide to aldehydes. AB - The asymmetric direct vinylogous aldol reaction of unactivated gamma-butenolide with aldehydes has been developed, giving the corresponding 5-(1' hydroxy)butenolide derivatives in high yields (up to 93%) and enantioselectivities (up to 83% ee) under mild conditions. PMID- 20590137 TI - Experimental and theoretical investigation of effect of spacer arm and support matrix of synthetic affinity chromatographic materials for the purification of monoclonal antibodies. AB - The aim of this study was to elucidate the influence of each material component the support, the spacer, and the surface chemistry-on the overall material performance of an affinity type purification media for the capture of immunoglobulin G (IgG). Material properties were investigated in terms of an experimental evaluation using affinity chromatography as well as computer modeling. The biomimetic triazine-based A2P affinity ligand was chosen as a fixed point, while spacer and support were varied. The investigated spacers were 1-2 diaminoethane (2LP), 1,3-propanedithiol (SS3), 3,6-dioxo-1,8-octanedithiol (DES), and a 1,4-substituted [1,2,3]-triazole spacer (TRZ). The support media considered were the agarose (AG) resins, PuraBead, the polyvinylether, Fractoprep, the polymethacrylate, Fractogel, and the porous silica, Fractosil. All materials were tested with pure IgG standard solution, with a mock feed solution as well as real cell culture supernatant. The interaction between IgG and A2P linked through the investigated spacers to AG was studied using molecular dynamics. The effect of a modification of the support chemical structure or of the protein-ligand binding site on the material performances was studied through target oriented simulations. Dynamic binding experiments (DBC) revealed that the performances of materials containing 2LP spacers were significantly decreased in the presence of Pluronic F68. The simulations indicated that this is probably determined by the establishment of intermolecular interactions between the 2LP charged amino group and the ether oxygen of Pluronic F68. The spacer giving the highest IgG dynamic binding capacity when Pluronic F68 was present in the feed was TRZ. The simulations showed that, among the investigated spacers, TRZ is the only one that prevents the adsorption of A2P on the support surface, thus suggesting that the mobility and lack of interaction of the ligand with the support is an important property for an affinity material. Both experiments and calculations agree that the chemistry of the support surface can have a significant impact on IgG binding, either affecting the IgG DBC, as found experimentally for materials having similar ligand densities and spacer arms but different supports, or competing with the affinity ligand when hydrophobic groups are added to the model surface, as was computationally predicted. PMID- 20590138 TI - 2,6-Disubstituted and 2,2,6-trisubstituted piperidines from serine: asymmetric synthesis and further elaboration. AB - 4-Hydroxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl esters, which are readily prepared from serine and terminal acetylenes, undergo Claisen rearrangement to piperidine derivatives when heated with butyl vinyl ether in the presence of Hg(OAc)(2) and Et(3)N. This route to optically pure piperidines having substituents alpha to nitrogen is general, and the rearrangement products are versatile intermediates for making a broad range of amines containing a substituted piperidine subunit. PMID- 20590139 TI - A novel, air-stable phosphine ligand for the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of chloro arenes. AB - A novel, air-stable phosphine ligand, prepared from readily available 2 bromonitrobenzene and vinylmagnesium bromide, combines with Pd(CH(3)CN)(2)Cl(2) to afford an effective catalyst for Suzuki-Miyaura cross-coupling of aryl, heteroaryl, and allyl chlorides with phenylboronic acid. PMID- 20590140 TI - Synthesis and characterization of NiSn dendrimer-encapsulated nanoparticles. AB - We report the synthesis and characterization of NiSn dendrimer-encapsulated nanoparticles (DENs) with sizes in the range of approximately 1.2 nm. These types of materials have potential applications in energy storage, and particles in the 1-3 nm size range are particularly attractive for this use. The NiSn DENs described here contain an average of 147 atoms and are encapsulated within hydrophobic, sixth-generation poly(amidoamine) dendrimers. DENs prepared using four different Ni/Sn ratios, along with monometallic Ni and Sn DENs, are described. To prevent oxidation, the synthesis was carried out under dry conditions in toluene. These bimetallic DENs were characterized by UV-vis spectroscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. The results indicate that the compositions of the nanoparticles reflect the ratio of Ni(2+) and Sn(2+) used in the first step of the synthesis; the NiSn nanoparticles remain encapsulated within the dendrimers, and when dry they have a degree of stability even after a short exposure to air. PMID- 20590142 TI - Toward the detection of cellular copper(II) by a light-activated fluorescence increase. PMID- 20590143 TI - Regioselective carboindation of simple alkenes with indium tribromide and ketene silyl acetals. AB - The regioselective carboindation of simple alkenes with indium tribromide and ketene silyl acetals was accomplished. Various alkenes such as ethylene, 1 alkenes, and cyclic alkenes were applicable for this reaction system. The alkylindium product from the carboindation of cyclohexene revealed an anti addition mechanism. PMID- 20590144 TI - Discrete and active enzyme nanoarrays on DNA origami scaffolds purified by affinity tag separation. AB - Desired enzyme nanoarrays patterned on a DNA origami scaffold were selectively isolated by affinity tag purification from a pool of differently patterned nanoarrays, and their enzymatic activity was successfully confirmed. As few as 12 histidine residues were enough to hold a huge complex of DNA origami with multiple proteins, 260 nm in length and 5.2 MDa in molecular weight, to an immobilized metal affinity resin. PMID- 20590145 TI - Insertion of carboryne into aromatic rings: formation of cyclooctatetraenocarboranes. AB - 1-Iodo-2-lithiocarborane is an efficient precursor to carboryne. It can react with arenes to give different types of dearomatization products, [4+2] cycloaddition and/or cycloinsertion products, dependent upon the substituents on the aromatic rings. The formal cycloinsertion products, cyclooctatetraenocarboranes, is generated from the [2+2] cycloaddition intermediates followed by thermal [3,3] sigmatropic rearrangement. This novel dearomatization of arenes with carboryne also serves as an important method for the synthesis of cyclooctatetraenocarboranes. PMID- 20590146 TI - Ab initio classical trajectory study of the fragmentation of C3H4 dications on the singlet and triplet surfaces. AB - Ab initio molecular dynamics have been used to examine the fragmentation of allene, propyne, and cyclopropene dications on the singlet and triplet potential energy surfaces. Accurate energies and barrier heights were computed at the CBS APNO level of theory. Classical trajectories were calculated at the B3LYP/6 31G(d,p) level of theory. To simulate vertical double ionizations of allene, propyne, and cyclopropene by short, intense laser pulses, the trajectories were started from the corresponding neutral geometries and were given ca. 240 kcal/mol excess kinetic energy; 200 trajectories were integrated for each case. Approximately one-third of the trajectories underwent extensive rearrangement before dissociation. Proton dissociation is the dominant pathway for all six cases, accounting for 50-75% of the trajectories. H(2)/H(2)(+) is produced in ca. 20% of the trajectories on the singlet propyne and cyclopropene dication surface. The calculated ratio of CH(+)/CH(2)(+)/CH(3)(+) compares favorably to that obtained in laser-induced Coulomb explosion of allene. The yield of CH(2)(+) is ca. 12% on the singlet and triplet allene dication surfaces compared to 6% or less in the other cases, whereas CH(+) is favored on the singlet propyne dication surface (12% vs 0-8% on the other surfaces). CH(3)(+) is formed primarily by direct dissociation on the triplet propyne dication surface (5% vs <1% on the other surfaces). The small amount of H(3)(+) seen experimentally for allene indicates that rearrangement can occur before dissociation. The dynamics simulations confirm that extensive isomerization occurs, even though the initial kinetic energy was too high to yield H(3)(+). PMID- 20590147 TI - Synthesis of beta-, gamma-, delta-, ..., omega-halogenated ketones and aldehydes. PMID- 20590148 TI - Antifungal and cytotoxic activity of withanolides from Acnistus arborescens. AB - Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy 4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro. PMID- 20590149 TI - Self-assembled graphene hydrogel via a one-step hydrothermal process. AB - Self-assembly of two-dimensional graphene sheets is an important strategy for producing macroscopic graphene architectures for practical applications, such as thin films and layered paperlike materials. However, construction of graphene self-assembled macrostructures with three-dimensional networks has never been realized. In this paper, we prepared a self-assembled graphene hydrogel (SGH) via a convenient one-step hydrothermal method. The SGH is electrically conductive, mechanically strong, and thermally stable and exhibits a high specific capacitance. The high-performance SGH with inherent biocompatibility of carbon materials is attractive in the fields of biotechnology and electrochemistry, such as drug-delivery, tissue scaffolds, bionic nanocomposites, and supercapacitors. PMID- 20590150 TI - Plasma-enhanced synthesis of bioactive polymeric coatings from monoterpene alcohols: a combined experimental and theoretical study. AB - This paper describes the synthesis and characterization of a novel organic polymer coating for the prevention of the growth of Pseudomonas aeruginosa on the solid surface of three-dimensional objects. Substrata were encapsulated with polyterpenol thin films prepared from terpinen-4-ol using radio frequency plasma enhanced chemical vapor deposition. Terpinen-4-ol is a constituent of tea tree oil with known antibacterial properties. The influence of deposition power on the chemical structure, surface composition, and ultimately the antibacterial inhibitory activity of the resulting polyterpenol thin films was studied using X ray photoelectron spectroscopy (XPS), water contact angle measurement, atomic force microscopy (AFM), and 3-D interactive visualization and statistical approximation of the topographic profiles. The experimental results were consistent with those predicted by molecular simulations. The extent of bacterial attachment and extracellular polymeric substances (EPS) production was analyzed using scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). Polyterpenol films deposited at lower power were particularly effective against P. aeruginosa due to the preservation of original terpinen-4-ol molecules in the film structure. The proposed antimicrobial and antifouling coating can be potentially integrated into medical and other clinically relevant devices to prevent bacterial growth and to minimize bacteria-associated adverse host responses. PMID- 20590151 TI - Effluent organic nitrogen (EON): bioavailability and photochemical and salinity mediated release. AB - The goal of this study was to investigate three potential ways that the soluble organic nitrogen (N) fraction of wastewater treatment plant (WWTP) effluents, termed effluent organic N (EON), could contribute to coastal eutrophication- direct biological removal, photochemical release of labile compounds, and salinity-mediated release of ammonium (NH4+). Effluents from two WWTPs were used in the experiments. For the bioassays, EON was added to water from four salinities (approximately 0 to 30) collected from the James River (VA) in August 2008, and then concentrations of N and phosphorus compounds were measured periodically over 48 h. Bioassay results, based on changes in DON concentrations, indicate that some fraction of the EON was removed and that the degree of EON removal varied between effluents and with salinity. Further, we caution that bioassay results should be interpreted within a broad context of detailed information on chemical characterization. EON from both WWTPs was also photoreactive, with labile NH4+ and dissolved primary amines released during exposure to sunlight. We also present the first data that demonstrate that when EON is exposed to higher salinities, increasing amounts of NH4+ are released, further facilitating EON use as effluent transits from freshwater through estuaries to the coast. PMID- 20590152 TI - The 480 nm system of KRb: 1 3Delta1, 4 1Sigma+, and 5 1Sigma+ states. AB - We have investigated the KRb 480 nm system by mass-resolved resonance enhanced two-photon ionization in a cold molecular beam. The 1 (3)Delta(1), 4 (1)Sigma(+), and 5 (1)Sigma(+) <-- X (1)Sigma(+) transitions have been identified. For the 1 (3)Delta(1) and 5 (1)Sigma(+) states, the electronic term values and vibrational constants are determined experimentally for the first time. Potential energy curves of the 4 (1)Sigma(+) and 5 (1)Sigma(+) states undergo multiple avoided crossings with nearby (1)Sigma(+) states in the observed spectral region. For the 4 (1)Sigma(+) state, a vibrational numbering of the experimentally observed levels is suggested. Anomalies in vibronic structures of the 4 (1)Sigma(+) and 5 (1)Sigma(+) states are understood by comparison with high-level ab initio calculations currently available. The avoided crossing energies are also experimentally estimated. PMID- 20590153 TI - Policy design and performance of emissions trading markets: an adaptive agent based analysis. AB - Emissions trading is considered to be a cost-effective environmental economic instrument for pollution control. However, the pilot emissions trading programs in China have failed to bring remarkable success in the campaign for pollution control. The policy design of an emissions trading program is found to have a decisive impact on its performance. In this study, an artificial market for sulfur dioxide (SO2) emissions trading applying the agent-based model was constructed. The performance of the Jiangsu SO2 emissions trading market under different policy design scenario was also examined. Results show that the market efficiency of emissions trading is significantly affected by policy design and existing policies. China's coal-electricity price system is the principal factor influencing the performance of the SO2 emissions trading market. Transaction costs would also reduce market efficiency. In addition, current-level emissions discharge fee/tax and banking mechanisms do not distinctly affect policy performance. Thus, applying emissions trading in emission control in China should consider policy design and interaction with other existing policies. PMID- 20590154 TI - A comparative study on chemical composition and antioxidant activity of ginger (Zingiber officinale) and cumin (Cuminum cyminum). AB - Spices are the building blocks of flavor in foods. This research work was focused on two important spices, i.e., ginger and cumin. Ginger and cumin both are recognized for their antioxidant properties. So, this study was designed to evaluate the chemical composition and antioxidant activity of ginger (Zingiber officinale) and cumin (Cuminum cyminum). The highest yield for volatile oil was obtained by the cumin sample, which was 2.52 +/- 0.11%, while the fresh ginger showed the lowest yield (0.31 +/- 0.08%). The analysis of volatile oils of fresh and dried ginger showed camphene, p-cineole, alpha-terpineol, zingiberene and pentadecanoic acid as major components, while the major components in cumin volatile oil were cuminal, gamma-terpinene and pinocarveol. In nonvolatile extracts the highest yield was obtained by the methanol extract of cumin (4.08 +/ 0.17% w/w), while the n-hexane extract of fresh ginger showed the lowest yield (0.52 +/- 0.03% w/w). Maximum total phenolic contents were observed in the methanol extract of fresh ginger (95.2 mg/g dry extract) followed by the hexane extract of fresh ginger (87.5 mg/g dry extract). The hexane extract of cumin showed the lowest total phenolic content (10.6 mg/g dry extract). The DPPH method showed the highest antioxidant activity for cumin essential oil (85.44 +/- 0.50%) followed by dried ginger essential oil (83.87 +/- 0.50%) and fresh ginger essential oil (83.03 +/- 0.54%). The FRAP of essential oils showed almost comparative results with DPPH. Cumin essential oil was found best in reducing Fe(3+) ions, followed by dried and fresh ginger. Our results suggest that both ginger and cumin can be used as potential sources of natural antioxidants in foods. PMID- 20590155 TI - Chemical synthesis of citrus flavanone glucuronides. AB - Flavanone glucuronides are the major phenolic metabolites detected in human plasma after consumption of citrus fruits. As such, they might display significant cardioprotective effects. In this work, glucuronides of naringenin (4'- and 7-O-beta-d-glucuronides) and hesperetin (3'- and 7-O-beta-d glucuronides), the major flavanone aglycones in grapefruit and orange, respectively, have been chemically synthesized. On the one hand, the most reactive hydroxyl group, C7-OH, was protected by selective benzoylation to allow subsequent glucuronidation of C4'-OH (naringenin) or C3'-OH (hesperetin) (B ring). On the other hand, the selective debenzoylation at C7-OH of the perbenzoylated flavanone aglycones allowed glucuronidation at the same position (A-ring). After careful deprotection, the target compounds were purified and characterized by nuclear magnetic resonance and mass spectrometry. PMID- 20590156 TI - Chitosan in nanostructured thin films. AB - This review paper brings an overview of the use of chitosans in nanostructured films produced with the Langmuir-Blodgett (LB) or the electrostatic layer-by layer (LbL) techniques, with emphasis on their possible applications. From a survey in the literature one may identify three main types of study with chitosan in nanostructured films. First, the interaction between chitosans and phospholipid Langmuir monolayers has been investigated for probing the mechanisms of chitosan action in their biological applications, with the monolayers serving as cell membrane models. In the second type, chitosan serves as a matrix for immobilization of biomolecules in LB as well as in LbL films, for which chitosan is suitable to help preserve the bioactivity of such biomolecules for long periods of time even in dry, solid films. An important application of these chitosan-containing films is in sensing and biosensing. The third type of study involves exploiting the mechanical and biocompatibility properties of chitosan in producing films with enhanced properties, for example, for tissue engineering. It is emphasized that chitosans have been proven excellent building blocks to produce films with controlled molecular architecture, allowing for synergy between distinct materials. We also discuss the prospects of the field, following a critical review of the latest developments in nanostructured chitosan films. PMID- 20590157 TI - Excited state charge transfer coupled double proton transfer reaction of 7 azaindole derivatives in methanol: a theoretical study. AB - Excited state charge transfer coupled excited state double proton transfer (ESCT/ESDPT) reaction in methanol (MeOH) for 3-cyano-7-azaindole(3-CNAI), 5-cyano 7-azaindole(5-CNAI), and 3,5-dicyano-7-azaindole(3,5-CNAI) were investigated using time-dependent density functional theory (TDDFT) method for the first time. The intermolecular hydrogen bonds of 3-CNAI-MeOH, 5-CNAI-MeOH, and 3,5-CNAI-MeOH complexes are demonstrated to be strengthened in the excited state and weakened in tautomer excited state, which indicates that reverse proton transfer reaction is not easy to take place. Due to the formation of intermolecular hydrogen bond, the absorption and excited state fluorescence spectra of the above three complexes are red-shifted in comparison with those of isolated molecules. The tautomer excited state fluorescence spectra that are induced by ESDPT reaction are also red-shifted relative to the excited state fluorescence for the above complexes. In addition, the sites where cyano group absorbed on 7-azaindole induces a large discrepancy of electron density distribution in excited state. Frontier molecular orbitals reflect that HOMO and LUMO orbitals of proton transfer PT-3-CNAI-MeOH, PT-5-CNAI-MeOH, and PT-3,5-CNAI-MeOH complexes are different with HOMO and LUMO orbitals of 3-CNAI-MeOH, 5-CNAI-MeOH, and 3,5-CNAI MeOH complexes, respectively. PMID- 20590158 TI - A new experimental method to determine the sorption isotherm of a liquid in a porous medium. AB - Sorption from the vapor phase is an important factor controlling the transport of volatile organic compounds (VOCs) in the vadose zone. Therefore, an accurate description of sorption behavior is essential to predict the ultimate fate of contaminants. Several measurement techniques are available in the case of water, however, when dealing with VOCs, the determination of sorption characteristics generally relies on gas chromatography. To avoid some drawbacks associated with this technology, we propose a new method to determine the sorption isotherm of any liquid compounds adsorbed in a soil. This method is based on standard and costless transducers (gas pressure, temperature) leading to a simple and transportable experimental device. A numerical estimation underlines the good accuracy and this technique is validated on two examples. Finally, this method is applied to determine the sorption isotherm of three liquid compounds (water, heptane, and trichloroethylene) in a clayey soil. PMID- 20590159 TI - Structural and functional analysis of the C-terminus of Galphaq in complex with the human thromboxane A2 receptor provides evidence of constitutive activity. AB - The human thromboxane A(2) (TXA(2)) receptor (TP) is known to mediate platelet aggregation and vasoconstriction. The receptor predominantly interacts with the Gq protein, thereby activating phospholipase C and increasing the intracellular calcium level. In this study, we synthesized a 15-residue peptide corresponding to the C-terminal domain of the Gq protein alpha subunit (Galphaq-Ct peptide) and characterized its interaction with recombinant TP purified from a baculovirus expression system in the presence and absence of an agonist using fluorescence and NMR spectroscopic studies. With fluorescence binding assays, we demonstrated that the Galphaq-Ct peptide was bound to TP, in the absence of the agonist, with a K(d) value of approximately 17 muM. Interestingly, upon addition of the agonist, U46619, the Galphaq-Ct peptide's binding affinity for this activated TP was reduced, thereby increasing the K(d) value to approximately 240 muM. NMR experiments demonstrated that the TP-bound Galphaq-Ct peptide shows a different affinity and conformation, in the absence and presence of the agonist, U46619. This suggested there is the possibility of ligand-free constitutive TP signaling through Galpha binding. Thus, an HEK293 cell line that stably expresses human TP and lacks the ability to produce TXA(2) was created by gene transfer and G418 selection. In comparison with the control cells, the stable cell line showed significant Galpha-mediated ligand-free calcium signaling. The study indicates a promising new outlook for the examination of prostanoid receptor-G-protein interactions in greater detail using integrated NMR spectroscopy, the purified receptor, and the stable cell line. PMID- 20590160 TI - Development of a fluorescence model for the binding of medium- to long-chain perfluoroalkyl acids to human serum albumin through a mechanistic evaluation of spectroscopic evidence. AB - A novel model for measuring the strength of perfluoroalkyl acid (PFAA) binding to human serum albumin (HSA) by use of the protein's native fluorescence is described. The model is derived from published properties of HSA and its interactions with other surfactants; it is consistent with these properties and experimental observations. The model's validity has been tested with both medium- to long-chain PFAAs (perfluoroheptanoate, perfluorooctanoate, perfluorononanoate, perfluorodecanoate, perfluoroundecanoate, perfluorohexanesulfonate, and perfluorooctanesulfonate) and short-chain PFAAs (perfluorohexanoate and perfluorobutanesulfonate). These experiments confirm the model as a valid description for the binding of medium- to long-chain PFAAs to HSA. Results indicate at least 2-3 PFAAs bind to each protein with affinity on the order of 10(4) M(-1). These binding strengths exhibit a dependence on protein concentration. Measured PFAA binding constants are approximately 10% of those values reported for fatty acids of similar chain length; correcting for protein concentration suggests the binding strengths may be as low as 2-3% of the corresponding fatty acids' affinities. Like fatty acids, the carboxylate PFAAs exhibit a trend of generally increasing binding strength with increased chain length. The model does not appear valid for the binding of short-chain PFAAs to HSA. Hill binding coefficients, fluorescence intensity measurements, and wavelengths of maximum emission suggest short-chain PFAAs associate with HSA differently and fail to promote the same conformational changes in the protein's tertiary structure as the medium- to long-chain PFAAs. PMID- 20590161 TI - Experimental methods for quantifying the activity of platinum electrocatalysts for the oxygen reduction reaction. AB - A tutorial is provided for methods to accurately and reproducibly determine the activity of Pt-based electrocatalysts for the oxygen reduction reaction in proton exchange membrane fuel cells and other applications. The impact of various experimental parameters on electrocatalyst activity is demonstrated, and explicit experimental procedures and measurement protocols are given for comparison of electrocatalyst activity to fuel cell standards. (To listen to a podcast about this article, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.). PMID- 20590162 TI - Pnc1p supports increases in cellular NAD(H) levels in response to internal or external oxidative stress. AB - Following transfer from medium with fermentable glucose to medium with nonfermentable acetate as the carbon source, cellular levels of NAD(H) were found to increase approximately 2-fold in a parental yeast strain. Similar transfer of a mutant strain subject to endogenous oxidative stress under these conditions produced more dramatic increases in cellular levels of NAD(H), and elevations above parental levels were shown to be due to the nicotinimidase Pnc1p. Similar transient increases in NAD(H) levels observed in the parental strain following addition of exogenous hydrogen peroxide were also attributable to Pnc1p. PMID- 20590163 TI - Critical role of membrane cholesterol in exocytosis revealed by single platelet study. AB - Exocytosis is a fundamental cellular process, pivotal in a wide range of cell types, used to deliver chemical messengers from one cell to another cell or tissue. While a tremendous amount of knowledge has been gained in the past several decades about the exocytotic machinery, recently it has become clear that the role of membrane lipids is also crucial in this process. In particular, the critical role of the abundant and ubiquitous cholesterol molecules has not been well-defined. Early insight has been gleaned from single cell amperometric studies on several commonly used secretory cell models, including chromaffin cells and PC12 cells; however, these secretory cell models are not ideal because manipulations of membrane cholesterol content may influence downstream cholesterol-dependent processes, making data interpretation difficult. Herein, blood platelets are employed as a simpler secretory cell model based on their anuclear nature and unique chemical messenger exocytosis behavior. Carbon-fiber microelectrochemistry was employed to measure real-time exocytosis from single platelets with depleted or enriched cholesterol either in the naturally occurring form or as the synthetic analogue epicholesterol. The experimental results show that membrane cholesterol directly modulates the secretion efficiency of individual platelets, as well as the kinetics of secretion events. Moreover, substitution of platelet membrane cholesterol with epicholesterol yields exocytotic behavior indistinguishable from that of normal platelets, arguing against the possibility of cholesterol-specific interactions in regulating exocytosis. It is clear from this work that membrane cholesterol plays a critical biophysical, rather than biochemical, role in platelet exocytosis and likely in exocytosis in general. PMID- 20590164 TI - Two-dimensional statistical recoupling for the identification of perturbed metabolic networks from NMR spectroscopy. AB - The development of Statistical Total Correlation Spectroscopy (STOCSY), a representation of the autocorrelation matrix of a spectral data set as a 2D pseudospectrum, has allowed more reliable assignment of one- and two-dimensional NMR spectra acquired from the complex mixtures that are usually used in metabolomics/metabonomics studies, thus, improving precise identification of candidate biomarkers contained in metabolic signatures computed by multivariate statistical analysis. However, the correlations obtained cannot always be interpreted in terms of connectivities between metabolites. In this study, we combine statistical recoupling of variables (SRV) and STOCSY to identify perturbed metabolite systems. The resulting Recoupled-STOCSY (R-STOCSY) method provides a 2D correlation landscape based on the SRV clusters representing physical, chemical, and biological entities. This enables the identification of correlations between distant clusters and extends the recoupling scheme of SRV, which was previously limited to the association of neighboring clusters. This allows the recovery of only meaningful correlations between metabolic signals and significantly enhances the interpretation of STOCSY. The method is validated through the measurement of the distances between the metabolites involved in these correlations, within the whole metabolic network, which shows that the average shortest path length is significantly shorter for the correlations detected in this new way compared to metabolite couples randomly selected from within the entire KEGG metabolic network. This enables the identification without any a priori knowledge of the perturbed metabolic network. The R-STOCSY completes the recoupling procedure between distant clusters, further reducing the high dimensionality of metabolomics/metabonomics data set and finally allows the identification of composite biomarkers, highlighting disruption of particular metabolic pathways within a global metabolic network. This allows the perturbed metabolic network to be extracted through NMR based metabolomics/metabonomics in an automated, and statistical manner. PMID- 20590166 TI - New hyperbranched conjugated polymers containing hexaphenylbenzene and oxadiazole units: convenient synthesis and efficient deep blue emitters for PLEDs application. AB - In this article, four "A(3)+B(2)+C(2)"-type hyperbranched conjugated polymers (P1 P4) containing hexaphenylbenzene as the core were synthesized successfully for the first time with high yields through one-pot Suzuki polymerization reaction. The copolymerization percent of 1,3,4-oxadiazole units was adjusted to investigate the effect of polymer composition on the physical, optical, and EL properties. All polymers were well-characterized and exhibited good solubility, film-forming ability, and thermal stability. Both the solution and the films of these hyperbranched polymers emitted pure and stable deep-blue light emission, and their PL spectra did not change after annealing at 150 degrees C for 0.5 h in air, indicating that the hyperbranched structure, coupled to the introduced hexaphenylbenzene moieties, effectively suppressed the formation of aggregation excimer and keto defects. Two-layer PLED devices were fabricated to investigate the electroluminescence properties of these hyperbranched polymers, and P3 demonstrated a maximum luminance efficiency of 0.72 cd/A and a maximum brightness of 549 cd/m(2) at 16.5 V. PMID- 20590167 TI - This Pediatric Drugs supplement updates the current knowledge about AOM in children, with a focus on the impact of resistance to antibacterial agents among the various causative species. Foreword. PMID- 20590165 TI - Quantification of beta-catenin signaling components in colon cancer cell lines, tissue sections, and microdissected tumor cells using reaction monitoring mass spectrometry. AB - Reaction monitoring mass spectrometry has emerged as a powerful tool for targeted detection and quantification of proteins in clinical samples. Here, we report the use of gel electrophoresis for protein fractionation and liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM) screening for quantitative analysis of components from the Wnt/beta-catenin signaling pathway, which contributes to colon tumor formation and progression. In silico tools are used to design LC-MRM screens for each target protein. Following successful peptide detection, stable isotope labeled peptides are synthesized and developed as internal standards. Then, the assays are implemented in colon cancer cell lines to achieve detection in minimal amounts of cells, compatible with direct translation to clinical specimens. Selected assays are compared with qualitative results from immunoblotting (Westerns) and translated to individual frozen colon tissue sections and laser capture microdissected tumor cells. This LC-MRM platform has been translated from in vitro models to clinical specimens, forming the basis for future experiments in patient assessment. PMID- 20590168 TI - Appropriate treatment of acute otitis media in the era of antibiotic resistance. AB - The outcome of treatment for acute otitis media (AOM) differs between various antibiotic drugs. Outcome depends upon the drugs' pharmacokinetics, but in the case of infectious diseases also on the susceptibility of the organism and the interaction between the drug and the organisms at the specific site of infection (pharmacodynamics). In the era of antibiotic resistance, it is thus important to understand the pharmacokinetics/pharmacodynamics of the various available drugs in the context of AOM and its main two pathogens, Streptococcus pneumoniae and non-typeable Haemophilus influenzae. In terms of clinical outcome, it is also important to realize that AOM is a self-limiting disease in most cases, so that response to treatment is always compared with the expected background response when not treated. A favourable clinical outcome (cure/improvement) at the end of the treatment period is expected for those in whom the pathogens are eradicated within 3-5 days, thus clinical failure rates are several fold lower in children with early eradication (within 3-5 days) compared with those in whom no early eradication takes place. Because of the higher spontaneous bacterial elimination this might not always be appreciated. In this review, the relationship between antibiotic resistance, the various antibiotic drugs and their pharmacokinetic/pharmacodynamic patterns, the bacteriological outcome and clinical outcomes are addressed. This review is meant to assist the clinician in both a better understanding of the current recommendations for the treatment of AOM and the steps to be taken to follow AOM patients. PMID- 20590170 TI - Communications: Evaluation of the nondiabaticity of quantum molecular dynamics with the dephasing representation of quantum fidelity. AB - We propose an approximate method for evaluating the importance of non-Born Oppenheimer effects on the quantum dynamics of nuclei. The method uses a generalization of the dephasing representation (DR) of quantum fidelity to several diabatic potential energy surfaces and its computational cost is the cost of dynamics of a classical phase space distribution. It can be implemented easily into any molecular dynamics program and also can utilize on-the-fly ab initio electronic structure information. We test the methodology on three model problems introduced by Tully and on the photodissociation of NaI. The results show that for dynamics close to the diabatic limit, the decay of fidelity due to nondiabatic effects is described accurately by the DR. In this regime, unlike the mixed quantum-classical methods such as surface hopping or Ehrenfest dynamics, the DR can capture more subtle quantum effects than the population transfer between potential energy surfaces. Hence we propose using the DR to estimate the dynamical importance of diabatic, spin-orbit, or other couplings between potential energy surfaces. The acquired information can help reduce the complexity of a studied system without affecting the accuracy of the quantum simulation. PMID- 20590171 TI - Communications: A systematic method for locating transition structures of A+B-->X type reactions. AB - Search for transition structures (TSs) as first-order saddles is one of the most important tasks in theoretical study of chemical reaction. Although automated search has been established either by starting from a local minimum (MIN) or by connecting two MINs, there is no systematic method which can locate TSs of A+B- >X(+Y) type reactions starting from separated reactants. We propose such an approach for the first time; it was demonstrated to work very well in the SN2, Diels-Alder, and Wittig reactions. PMID- 20590169 TI - The Viriato study: update on antimicrobial resistance of microbial pathogens responsible for community-acquired respiratory tract infections in Portugal. AB - The Viriato study is a prospective, multicentre laboratory-based surveillance study of antimicrobial susceptibility in which 30 microbiology laboratories throughout Portugal are asked to isolate, identify and submit to a central laboratory for testing Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis responsible for community-acquired lower respiratory tract infections and Streptococcus pyogenes from tonsillitis. To monitor changes in antimicrobial resistance patterns of these frequent respiratory pathogens. Susceptibility was determined by disk diffusion (Kirby-Bauer) or using Etest strips following the Clinical and Laboratory Standards Institute guidelines. From 1999 to 2007 over 13 900 isolates were analysed. Among S. pneumoniae penicillin non-susceptibility decreased from 25% in 1999 to 18% in 2007 (p = 0.002) but resistance to macrolides showed a steady increase, reaching 20% in the last 6 years. Resistance to amoxicillin and the quinolones remained stable and very low (1-2%) throughout the study period. Antimicrobial resistance among H. influenzae and M. catarrhalis remained stable. The most significant resistance was to ampicillin, of 10-12% and greater than 80%, respectively, as a result of the production of beta-lactamases. Macrolide resistance among S. pyogenes was stable during 1999-2003 (20-23%) but after 2003 there was a steady decline in resistance, which in 2007 reached 10%. The Viriato surveillance study showed that penicillin remains the most active antimicrobial agent against S. pyogenes causing tonsillitis, and amoxicillin-clavulanate and the quinolones are the most active in vitro simultaneously against S. pneumoniae, H. influenzae and M. catarrhalis responsible for community-acquired lower respiratory tract infections in Portugal. PMID- 20590172 TI - Communications: Chain and double-ring polymeric structures: Observation of Al(n)H(3n+1) (-) (n=4-8) and Al(4)H(14) (-). AB - A pulsed arc discharge source was used to prepare gas-phase, aluminum hydride cluster anions, Al(n)H(m) (-), exhibiting enhanced hydrogen content. The maximum number of hydrogen atoms in Al(n)H(m) (-) species was m=3n+1 for n=5-8, i.e., Al(n)H(3n+1) (-), and m=3n+2 for n=4, i.e., Al(4)H(14) (-), as observed in their mass spectra. These are the most hydrogen-rich aluminum hydrides to be observed thus far, transcending the 3:1 hydrogen-to-aluminum ratio in alane. Even more striking, ion intensities for Al(n)H(m) (-) species with m=3n+1 and m=3n+2 hydrogen atoms were significantly higher than those of nearby Al(n)H(m) (-) mass peaks for which m<3n+1, i.e., the ion intensities for Al(n)H(3n+1) (-) and for Al(4)H(14) (-) deviated from the roughly bell-shaped ion intensity patterns seen for most Al(n)H(m) (-) species, in which m ranges from 1 to 3n. Calculations based on density functional theory showed that Al(n)H(3n+1) (-) clusters have chain and/or double-ring polymeric structures. PMID- 20590173 TI - Communications: Ab initio second-order nonlinear optics in solids. AB - We present a first-principles theory for the calculation of the macroscopic second-order susceptibility chi((2)), based on the time-dependent density functional theory approach. Our method allows to include straightforwardly the many-body effects, such as crystal local fields and excitons. We apply the theory to the computation of the second-harmonic generation spectroscopy. In order to demonstrate the accuracy of this approach we present spectra for the cubic semiconductor GaAs for which we obtain a very good agreement with the experimental results. We point out that crystal local fields are not sufficient to reproduce the experimental results. Only when we account for the excitonic effects we obtain a very good agreement with the experimental second-harmonic generation spectrum. PMID- 20590174 TI - Communications: Signatures of quasiparticle entanglement in multidimensional nonlinear optical spectroscopy of aggregates. AB - Excitons represent collective optical excitations in which the motions of electrons belonging to different chromophores are correlated. We discuss the utility of the notion of entanglement commonly used in quantum information processing, in the description of these excitations. A distinction is made between some apparent entanglement effects associated with the linear response that may be removed by a transformation of coordinates and can be handled classically, and genuine entanglement that is fundamentally quantum in nature and shows up only in the nonlinear optical response. PMID- 20590176 TI - Non-Born-Oppenheimer quantum chemistry on the fly with continuous path branching due to nonadiabatic and intense optical interactions. AB - We extend our formerly proposed theory for non-Born-Oppenheimer electronic and nuclear wavepacket dynamics within on-the-fly scheme [T. Yonehara, S. Takahashi, and K. Takatsuka, J. Chem. Phys. 130, 214113 (2009)] to a case of nonadiabatic dynamics under an intense laser field: electron wavepacket in a molecule is propagated in attosecond time-scale along non-Born-Oppenheimer nuclear paths that smoothly branch due to nonadiabatic coupling and/or optical interactions. Such branching paths are determined consistently with the motion of the electron wavepackets. Furthermore, these nuclear paths are quantized in terms of Gaussian wavepackets (action decomposed function), which can be applied to nonclassical paths. Both electronic wavepacket dynamics and quantization of non-Born Oppenheimer paths are generalized so as to include the direct effects of the classical vector potential of electromagnetic fields. In the second half of this paper, we perform numerical studies to explore nonadiabatic dynamics in a laser field by examining two cases: one is a two-state model system having an avoided crossing, and the other is two-state dynamics in HF molecule on the two low lying ab initio potential curves. Both are placed in laser fields. With the former system, we survey some basic properties of the coupling of nonadiabatic dynamics and laser interaction varying the relevant coupling parameters such as the laser timing with respect to the incident of nonadiabatic transition. This investigation will set a foundation for the future studies of control of electronic states in realistic multidimensional molecular systems. Application to the latter system shows that non-Born-Oppenheimer quantum chemistry in laser fields is indeed useful in the study of dynamics in ab initio level. Through the comparison with full quantum data, we verify that the formalism and methodology developed here work accurately. Furthermore, we attain some basic insight about the characteristics of molecules in laser fields. PMID- 20590177 TI - An efficient iterative grand canonical Monte Carlo algorithm to determine individual ionic chemical potentials in electrolytes. AB - Two iterative procedures have been proposed recently to calculate the chemical potentials corresponding to prescribed concentrations from grand canonical Monte Carlo (GCMC) simulations. Both are based on repeated GCMC simulations with updated excess chemical potentials until the desired concentrations are established. In this paper, we propose combining our robust and fast converging iteration algorithm [Malasics, Gillespie, and Boda, J. Chem. Phys. 128, 124102 (2008)] with the suggestion of Lamperski [Mol. Simul. 33, 1193 (2007)] to average the chemical potentials in the iterations (instead of just using the chemical potentials obtained in the last iteration). We apply the unified method for various electrolyte solutions and show that our algorithm is more efficient if we use the averaging procedure. We discuss the convergence problems arising from violation of charge neutrality when inserting/deleting individual ions instead of neutral groups of ions (salts). We suggest a correction term to the iteration procedure that makes the algorithm efficient to determine the chemical potentials of individual ions too. PMID- 20590175 TI - Enhanced sampling and applications in protein folding in explicit solvent. AB - We report a single-copy tempering method for simulating large complex systems. In a generalized ensemble, the method uses runtime estimate of the thermal average energy computed from a novel integral identity to guide a continuous temperature space random walk. We first validated the method in a two-dimensional Ising model and a Lennard-Jones liquid system. It was then applied to folding of three small proteins, trpzip2, trp-cage, and villin headpiece in explicit solvent. Within 0.5 1 microsecond, all three systems were reversibly folded into atomic accuracy: the alpha carbon root mean square deviations of the best folded conformations from the native states were 0.2, 0.4, and 0.4 A, for trpzip2, trp-cage, and villin headpiece, respectively. PMID- 20590178 TI - Weak antiferromagnetic coupling in molecular ring is predicted correctly by density functional theory plus Hubbard U. AB - We apply density functional theory with empirical Hubbard U parameter (DFT+U) to study Mn-based molecular magnets. Unlike most previous DFT+U studies, we calibrate U parameters for both metal and ligand atoms using five binuclear manganese complexes as the benchmarks. We note delocalization of the spin density onto acetate ligands due to pi-back bonding, inverting spin polarization of the acetate oxygen atoms relative to that predicted from superexchange mechanism. This inversion may affect the performance of the models that assume strict localization of the spins on magnetic centers for the complexes with bridging acetate ligands. Next, we apply DFT+U methodology to Mn(12) molecular wheel and find antiparallel spin alignment for the weakly interacting fragments Mn(6), in agreement with experimental observations. Using the optimized geometry of the ground spin state instead of less accurate experimental geometry was found to be crucial for this good agreement. The protocol tested in this study can be applied for the rational design of single molecule magnets for molecular spintronics and quantum computing applications. PMID- 20590179 TI - Nonequilibrium numerical model of homogeneous condensation in argon and water vapor expansions. AB - A computational approach capable of modeling homogeneous condensation in nonequilibrium environments is presented. The approach is based on the direct simulation Monte Carlo (DSMC) method, extended as appropriate to include the most important processes of cluster nucleation and evolution at the microscopic level. The approach uses a recombination-reaction energy-dependent mechanism of the DSMC method for the characterization of dimer formation, and the RRK model for the cluster evaporation. Three-step testing and validation of the model is conducted by (i) comparison of clusterization rates in an equilibrium heat bath with theoretical predictions for argon and water vapor and adjustment of the model parameters, (ii) comparison of the nonequilibrium argon cluster size distributions with experimental data, and (iii) comparison of the nonequilibrium water cluster size distributions with experimental measurements. Reasonable agreement was observed for all three parts of the validation. PMID- 20590180 TI - Calculation of the first static hyperpolarizability tensor of three-dimensional periodic compounds with a local basis set: A comparison of LDA, PBE, PBE0, B3LYP, and HF results. AB - The computational scheme for the evaluation of the second-order electric susceptibility tensor in periodic systems, recently implemented in the CRYSTAL code within the coupled perturbed Hartree-Fock (HF) scheme, has been extended to local-density, gradient-corrected, and hybrid density functionals (coupled perturbed Kohn-Sham) and applied to a set of cubic and hexagonal semiconductors. The method is based on the use of local basis sets and analytical calculation of derivatives. The high-frequency dielectric tensor (epsilon(infinity)) and second harmonic generation susceptibility (d) have been calculated with hybrid functionals (PBE0 and B3LYP) and the HF approximation. Results are compared with the values of epsilon(infinity) and d obtained from previous plane-wave local density approximation or generalized gradient approximation calculations and from experiment. The agreement is in general good, although comparison with experiment is affected by a certain degree of uncertainty implicit in the experimental techniques. PMID- 20590181 TI - Efficient evaluation of the Coulomb force in the Gaussian and finite-element Coulomb method. AB - We propose an efficient method for evaluating the Coulomb force in the Gaussian and finite-element Coulomb (GFC) method, which is a linear-scaling approach for evaluating the Coulomb matrix and energy in large molecular systems. The efficient evaluation of the analytical gradient in the GFC is not straightforward as well as the evaluation of the energy because the SCF procedure with the Coulomb matrix does not give a variational solution for the Coulomb energy. Thus, an efficient approximate method is alternatively proposed, in which the Coulomb potential is expanded in the Gaussian and finite-element auxiliary functions as done in the GFC. To minimize the error in the gradient not just in the energy, the derived functions of the original auxiliary functions of the GFC are used additionally for the evaluation of the Coulomb gradient. In fact, the use of the derived functions significantly improves the accuracy of this approach. Although these additional auxiliary functions enlarge the size of the discretized Poisson equation and thereby increase the computational cost, it maintains the near linear scaling as the GFC and does not affects the overall efficiency of the GFC approach. PMID- 20590182 TI - Range-separated density-functional theory with random phase approximation applied to noncovalent intermolecular interactions. AB - Range-separated methods combining a short-range density functional with long range random phase approximations (RPAs) with or without exchange response kernel are tested on rare-gas dimers and the S22 benchmark set of weakly interacting complexes of Jurecka et al. [Phys. Chem. Chem. Phys. 8, 1985 (2006)]. The methods are also compared to full-range RPA approaches. Both range separation and inclusion of the Hartree-Fock exchange kernel largely improve the accuracy of intermolecular interaction energies. The best results are obtained with the method called RSH+RPAx, which yields interaction energies for the S22 set with an estimated mean absolute error of about 0.5-0.6 kcal/mol, corresponding to a mean absolute percentage error of about 7%-9% depending on the reference interaction energies used. In particular, the RSH+RPAx method is found to be overall more accurate than the range-separated method based on long-range second-order Moller Plesset (MP2) perturbation theory (RSH+MP2). PMID- 20590183 TI - Using fit functions in computational dielectric spectroscopy. AB - This work deals with the development of an appropriate set of fit functions for describing dielectric spectra based on simulated raw data. All these fit functions are of exponential character with properly chosen cofunctions. The type of the cofunctions is different for translation, rotation and their coupling. As an alternative to multiexponential fits we also discuss Kohlrausch-Williams-Watts functions. Since the corresponding Fourier-Laplace series for these stretched exponentials has severe convergence problems, we represent their Fourier-Laplace spectrum as a Havriliak-Negami expression with properly chosen parameters. A general relation between the parameter of the Kohlrausch-Williams-Watts and the Havriliak-Negami parameters is given. The set of fit functions is applied to the concrete simulation of the hydrated ionic liquid 1-ethyl-3-methyl-imidazolium triflate with H(2)O. The systematic variation of the water mole fraction permits to study the gradual transition from a neutral molecular liquid to molecular ionic liquids. PMID- 20590184 TI - Semiclassical initial value approximation for Green's function. AB - A semiclassical initial value approximation is obtained for the energy-dependent Green's function. For a system with f degrees of freedom the Green's function expression has the form of a (2f-1)-dimensional integral over points on the energy surface and an integral over time along classical trajectories initiated from these points. This approximation is derived by requiring an integral ansatz for Green's function to reduce to Gutzwiller's semiclassical formula when the integrations are performed by the stationary phase method. A simpler approximation is also derived involving only an (f-1)-dimensional integral over momentum variables on a Poincare surface and an integral over time. The relationship between the present expressions and an earlier initial value approximation for energy eigenfunctions is explored. Numerical tests for two dimensional systems indicate that good accuracy can be obtained from the initial value Green's function for calculations of autocorrelation spectra and time independent wave functions. The relative advantages of initial value approximations for the energy-dependent Green's function and the time-dependent propagator are discussed. PMID- 20590185 TI - Nonadiabatic dynamics with the help of multiconfigurational Ehrenfest method: Improved theory and fully quantum 24D simulation of pyrazine. AB - This article proposes an improved version of recently developed multiconfigurational Ehrenfest approach to quantum dynamics. The idea of the approach is to use frozen Gaussians (FG) guided by Ehrenfest trajectories as a basis set for fully quantum propagation. The method is applied to simulation of nonadiabatic dynamics of pyrazine and shows that nonadiabatic dynamics on two coupled electronic states S(2) and S(1), which determines pyrazine absorption spectrum, can be simulated with the help of a basis comprised of very small number of trajectory guided basis functions. For the 24 dimensional (24D) model, good results were obtained with the basis of only 250 trajectories guided FG per electronic state. The efficiency of the method makes it particularly suitable for future application together with direct dynamics, calculating potentials on the fly. PMID- 20590186 TI - Matrix-free application of Hamiltonian operators in Coifman wavelet bases. AB - A means of evaluating the action of Hamiltonian operators on functions expanded in orthogonal compact support wavelet bases is developed, avoiding the direct construction and storage of operator matrices that complicate extension to coupled multidimensional quantum applications. Application of a potential energy operator is accomplished by simple multiplication of the two sets of expansion coefficients without any convolution. The errors of this coefficient product approximation are quantified and lead to use of particular generalized coiflet bases, derived here, that maximize the number of moment conditions satisfied by the scaling function. This is at the expense of the number of vanishing moments of the wavelet function (approximation order), which appears to be a disadvantage but is shown surmountable. In particular, application of the kinetic energy operator, which is accomplished through the use of one-dimensional (1D) [or at most two-dimensional (2D)] differentiation filters, then degrades in accuracy if the standard choice is made. However, it is determined that use of high-order finite-difference filters yields strongly reduced absolute errors. Eigensolvers that ordinarily use only matrix-vector multiplications, such as the Lanczos algorithm, can then be used with this more efficient procedure. Applications are made to anharmonic vibrational problems: a 1D Morse oscillator, a 2D model of proton transfer, and three-dimensional vibrations of nitrosyl chloride on a global potential energy surface. PMID- 20590188 TI - First-principles studies for CO and O(2) on gold nanocluster. AB - First-principles calculations are performed to study the interaction of gold nanocluster Au(55) with small molecules CO and O(2). We find that the adsorption energy of CO on Au(55) is among 0.5-0.7 eV at different sites and [CO+O(2)] can be coadsorbed on Au(55). Comparisons between Au(55) and Au(32) show that the adsorption energy not only depends on the size of the cluster but also on the geometry of the cluster. Similar with smaller cluster (Au(8) and Au(32)), the energy difference between [CO+O(2)] and [CO(2)+O] on Au(55) is much larger than that in the free gas. Our calculations indicate that the nanocluster Au(55) can enhance the reaction process, CO+O(2)-->CO(2)+O, in which the reaction barrier is only about half electron volts. PMID- 20590187 TI - Isotope dependent, temperature regulated, energy repartitioning in a low-barrier, short-strong hydrogen bonded cluster. AB - We investigate and analyze the vibrational properties, including hydrogen/deuterium isotope effects, in a fundamental organic hydrogen bonded system using multiple experimental (infrared multiple photon dissociation and argon-tagged action spectroscopy) and computational techniques. We note a qualitative difference between the two experimental results discussed here and employ ab initio molecular dynamics simulations to explain these results. A deeper understanding of the differences between the isotopically labeled systems arises from an analysis of the simulated cluster spectroscopy and leads to a system-bath coupling interpretation. Specifically, when a few active modes, involving the shared hydrogen/deuterium stretch, are identified and labeled as "system," with all other molecular vibrational modes being identified as "bath" modes, we find critical differences in the coupling between the system modes for the shared proton and shared deuteron cases. These differences affect the energy repartitioning between these modes resulting in a complex spectral evolution as a function of temperature. Furthermore, intensity borrowing across modes that are widely distributed in the frequency domain plays an important role on the simulated spectra. PMID- 20590189 TI - A path-integral Monte Carlo study of a small cluster: The Ar trimer. AB - The Ar(3) system has been studied between T=0 K and T=40 K by means of a path integral Monte Carlo (PIMC) method. The behavior of the average energy in terms of the temperature has been explained by comparison with results obtained with the thermal averaged rovibrational spectra estimated via: (i) a quantum mechanical method based on distributed Gaussian functions for the interparticle distances and (ii) an analytical model which precisely accounts for the participation of the dissociative continua Ar(2)+Ar and Ar+Ar+Ar. Beyond T approximately 20 K, the system explores floppier configurations than the rigid equilateral geometry, as linear and Ar-Ar(2)-like arrangements, and fragmentates around T approximately 40 K. A careful investigation of the specific heat in terms of a confining radius in the PIMC calculation seems to discard a proper phase transition as in larger clusters, in apparent contradiction with previous reports of precise values for a liquid-gas transition. The onset of this noticeable change in the dynamics of the trimer occurs, however, at a remarkably low value of the temperature in comparison with Ar(n) systems formed with more Ar atoms. Quantum mechanical effects are found of relevance at Tns and 5p-->nd excitations are observed in both the first PE band, I(+)((3)P(2))<--I((2)P(3/2)), and the fourth PE band, I(+)((1)D(2))<--I((2)P(3/2)), CIS spectra. For each Rydberg state, the resonance energy, quantum defect, linewidth, line shape, and photoelectron angular distribution parameter beta have been determined. For the beta-plots for each PE band, only resonances corresponding to 5p-->nd excitations are observed; no resonances were seen at photon energies corresponding to the 5p-->ns resonances in the CIS spectra. The beta-plots are interpreted in terms of the parity unfavored channel with j(t)=4 being the major contributor at the 5p-->nd resonance positions, where j(t) is the quantum number for angular momentum transferred between the molecule, and the ion and photoelectron. Comparison of the results obtained with those published for bromine shows reasonably good agreement for the CIS spectra but poor agreement for the beta-plots. It appears that parity unfavored channels are playing a greater role in the valence (np)(-1) ionization of atomic iodine than in the corresponding ionization of atomic bromine. PMID- 20590191 TI - Long range intermolecular interactions between the alkali diatomics Na(2), K(2), and NaK. AB - Long range interactions between the ground state alkali diatomics Na(2)-Na(2), K(2)-K(2), Na(2)-K(2), and NaK-NaK are examined. Interaction energies are first determined from ab initio calculations at the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory, including counterpoise corrections. Long range energies calculated from diatomic molecular properties (polarizabilities and dipole and quadrupole moments) are then compared with the ab initio energies. A simple asymptotic model potential E(LR)=E(elec)+E(disp)+E(ind) is shown to accurately represent the intermolecular interactions for these systems at long range. PMID- 20590192 TI - The low-lying states of the scandium dimer. AB - A systematic investigation of low-lying states of Sc(2) using multireference perturbation theory (NEVPT2 and NEVPT3) indicates that the ground state of this system is (5)Sigma(u) (-) with r(e)=2.611 A, omega(e)=241.8 cm(-1), and D(e)=1.78 eV. This state is closely followed by other low-lying states of Sc(2): (3)Sigma(u) (-), (5)Delta(u), (3)Pi(g), (1)Pi(g), and (1)Sigma(u) (-). Our energy ordering of the (5)Sigma(u) (-) and (3)Sigma(u) (-) states confirms the recent MRCI results of Kalemos et al. [J. Chem. Phys. 132, 024309 (2010)] and is at variance with the earlier diffusion Monte Carlo predictions of Matxain et al. [J. Chem. Phys. 128, 194315 (2008)]. An excellent agreement between the second- and third-order NEVPT results and between the computed and experimental values of omega(e) (241.8 versus 238.9 cm(-1)) for the (5)Sigma(u) (-) state suggests high accuracy of our predictions. PMID- 20590193 TI - Insights into the ultraviolet spectrum of liquid water from model calculations. AB - With a view toward a better molecular level understanding of the effects of hydrogen bonding on the ultraviolet absorption spectrum of liquid water, benchmark electronic structure calculations using high level wave function based methods and systematically enlarged basis sets are reported for excitation energies and oscillator strengths of valence excited states in the equilibrium water monomer and dimer and in a selection of liquid-like dimer structures. Analysis of the electron density redistribution associated with the two lowest valence excitations of the water dimer shows that these are usually localized on one or the other monomer, although valence hole delocalization can occur for certain relative orientations of the water molecules. The lowest excited state is mostly associated with the hydrogen bond donor and the significantly higher energy second excited state mostly with the acceptor. The magnitude of the lowest excitation energies is strongly dependent on where the valence hole is created, and only to a lesser degree on the perturbation of the excited electron density distribution by the neighboring water molecule. These results suggest that the lowest excitation energies in clusters and liquid water can be associated with broken acceptor hydrogen bonds, which provide energetically favorable locations for the formation of a valence hole. Higher valence excited states of the dimer typically involve delocalization of the valence hole and/or delocalization of the excited electron and/or charge transfer. Two of the higher valence excited states that involve delocalized valence holes always have particularly large oscillator strengths. Due to the pervasive delocalization and charge transfer, it is suggested that most condensed phase water valence excitations intimately involve more than one water molecule and, as a consequence, will not be adequately described by models based on perturbation of free water monomer states. The benchmark calculations are further used to evaluate a series of representative semilocal, global hybrid, and range separated hybrid functionals used in efficient time-dependent density functional methods. It is shown that such an evaluation is only meaningful when comparison is made at or near the complete basis set limit of the wave function based reference method. A functional is found that quantitatively describes the two lowest excitations of water dimer and also provides a semiquantitative description of the higher energy valence excited states. This functional is recommended for use in further studies on the absorption spectrum of large water clusters and of condensed phase water. PMID- 20590194 TI - Measurement of the differential cross section of the photoinitiated reactive collision of O((1)D)+D(2) using only one molecular beam: A study by three dimensional velocity mapping. AB - In order to measure the state selective double differential cross section of a reactive collision, the preparation of the reactants with defined initial velocities and quantum states in number densities high enough to achieve an acceptable count rate is most important. At the same time, secondary collisions have to be prevented in order to ensure that the nascent products are not thermalized. Usually, the best way to control the initial conditions is to use crossed molecular beams, but the number density decreases quadratically with the distance from the nozzle orifice which can be a problem, especially if a molecular product with a large number of populated states is to be analyzed state specifically by REMPI spectroscopy. In this contribution we would like to present a method for measuring the quantum state selective differential cross section of a photoinitiated reaction that combines the advantages of the PHOTOLOC technique (high reactant densities) and the parallel beams technique used by the groups of Kitsopoulos, Orr-Ewing, and Suits (defined relative velocity of the reactants). Moreover, an algorithm based on a Bayesian backward reconstruction developed by W. H. Richardson [J. Opt. Soc. Am. 62, 55 (1972)] has been derived. Both, one reactant and the precursor of the other reactant, are present in the same molecular beam and the center of mass velocity is selected by shifting the dissociation and the detection laser in time and space. Like in comparable methods, this produces a bias in the measured velocity distribution due to the fact that the reaction takes place in the whole volume surrounding the laser beams. This has been also reported by Toomes et al. in the case of the parallel beams technique and presents a general problem of probing reaction products by REMPI spectroscopy. To account for this, we develop a general approach that can be easily adapted to other conditions. The bias is removed in addition to deconvolution from the spread in reactant velocities. Using the benchmark system O((1)D)+D(2) with N(2)O as the precursor, we demonstrate that the technique is also applicable in a very general sense (i.e., also with a large spread in reactant velocities, products much faster than reactants) and therefore can be used also if such unfortunate conditions cannot be avoided. Since the resulting distribution of velocities in the laboratory frame is not cylindrically symmetric, three dimensional velocity mapping is the method of choice for the detection of the ionized products. For the reconstruction, the distance between the two laser beams is an important parameter. We have measured this distance using the photodissociation of HBr at 193 nm, detecting the H atoms near 243 nm. The collision energy resulting from the 193 nm photodissociation of N(2)O is 5.2+/-1.9 kcal/mol. Our results show a preference for backward scattered D atoms with the OH partner fragment in the high vibrational states (v=4-6), in accord with previously published results claiming the growing importance of a linear abstraction mechanism for collision energies higher than 2.4 kcal/mol. PMID- 20590195 TI - Predissociation dynamics of N(2)O(+) at the A (2)Sigma(+) state: Three pathways to form NO(+)((1)Sigma(+)) revealed from ion velocity imaging. AB - The predissociation dynamics of nitrous oxide ion (N(2)O(+)) at its first excited state A (2)Sigma(+) has been investigated with ion velocity imaging by probing the NO(+) fragments. The parent ion N(2)O(+), prepared at the ground state X (2)Pi(000) through (3+1) resonance-enhanced multiphoton ionization (REMPI) of jet cooled N(2)O molecules at 360.55 nm, was excited to different vibrational levels of the A (2)Sigma(+) state in a wavelength range of 280-320 nm, and then predissociated to form NO(+) and N fragments. The internal energy distribution of the NO(+) fragment was determined from its ion velocity images. With the help of potential energy surfaces (PESs) of N(2)O(+), three dissociation pathways have been proposed to interpret the three kinds of NO(+) fragments with different internal state distributions: (1) the A (2)Sigma(+) state couples to a dissociative 1 (4)Sigma(-) state via a bound 1 (4)Pi state to form the NO(+)+N((4)S) channel, where NO(+) fragment is rotationally hot; (2) the A (2)Sigma(+) state couples to dissociative states (2)Sigma(-)/(2)Delta via the 1 (4)Pi state to form the NO(+)+N((2)D) channel, where NO(+) fragment is also rotationally hot; (3) the A (2)Sigma(+) state couples to the high energy region of the ground state X (2)Pi and then dissociates to form the NO(+)+N((2)D) channel, where NO(+) is rotationally cold. PMID- 20590196 TI - Site-dependent photodissociation of vibronically excited CD(3)NH(2) molecules. AB - The mechanism of H and D atom loss, following ultraviolet photolysis of methylamine-d(3), CD(3)NH(2), has been studied via electronic action and Doppler spectroscopies. The N-H bond is preferentially cleaved and the yield of both H and D photofragments increases gradually, but differently, as higher vibrational states on the first excited electronic state, A, are accessed, leading to some drop in H/D branching ratios. The average translational energies of the H photofragments are somewhat higher than those of D, implying lower energy content left in the internal degrees of freedom of the CD(3)NH than in the CD(2)NH(2) partner fragment. These results provide evidence for discrimination between the two channels and mechanistic insight into the N-H and C-D bond cleavage. PMID- 20590197 TI - Field-free molecular orientation with terahertz few-cycle pulses. AB - We demonstrate theoretically an efficient field-free orientation in LiH and LiCl driven by available terahertz few-cycle pulses (TFCPs). Exact results by numerically solving the time-dependent Schrodinger equation including the vibrational and rotational degrees of freedom are compared to the rigid-rotor approximation (RRA) as well as to the impulsive approximation (IA), and the effect of rotational-vibrational coupling on the both RRA and IA is examined in detail. We find that the current available TFCPs may overcome the technical limitation of terahertz half-cycle pulse for enhancing the field-free molecular orientation. PMID- 20590198 TI - Velocity map imaging the dynamics of the reactions of Cl atoms with neopentane and tetramethylsilane. AB - The reactions of ground state Cl((2)P(3/2)) atoms with neopentane and tetramethylsilane have been studied at collision energies of 7.9+/-2.0 and 8.2+/ 2.0 kcal mol(-1), respectively. The nascent HCl(v=0,J) products were probed using resonance enhanced multiphoton ionization spectroscopy combined with velocity map imaging (VMI) to determine the rotational level population distributions, differential cross sections (DCSs), and product translational energy distributions. The outcomes from PHOTOLOC and dual beam methods are compared and are discussed in light of previous studies of the reactions of Cl atoms with other saturated hydrocarbons, including a recent crossed molecular beam and VMI investigation of the reaction of Cl atoms with neopentane [Estillore et al., J. Chem. Phys. 132, 164313 (2010)]. Rotational distributions were observed to be cold, consistent with the reactions proceeding via a transition state with a collinear Cl-H-C moiety. The DCSs for both reactions are forward peaked but show scatter across a broad angular range. Interpretation using a model based on linear dependence of scattering angle on impact parameter indicates that the probability of reaction is approximately constant across all allowed impact parameters. Product translational energy distributions from dual beam experiments have mean values, expressed as fractions of the total available energy, of 0.67 (Cl+neopentane) and 0.64 (Cl+tetramethylsilane) that are consistent with a kinematic model for the reaction in which the translational energy of the reactants is conserved into product translational energy. PMID- 20590199 TI - Molecular anion formation in 9,10-anthraquinone: Dependence of the electron detachment rate on temperature and incident electron energy. AB - Attachment of low-energy electrons to gas phase 9,10-anthraquinone (AQ) was observed with electron transmission (ET) spectroscopy, and interpreted with the support of quantum chemical calculations. The ET spectrum displays three shape resonances at 0.45, 0.7, and 2.2 eV, associated with temporary electron capture into empty pi( *) molecular orbitals of AQ, the first two anion states being stable. According to TD-B3LYP calculations, the first pi-pi( *) core-excited resonance lies at about 1.8 eV, although no experimental evidence for this anion state was found. The long-lived parent molecular anion [AQ](-) was observed by means of Electron Attachment Spectroscopy (EAS) using two different mass spectrometers and also by measuring the total anion current at the collision chamber walls. The molecular anion current shows maxima at zero energy, around 0.6 eV and at 1.8 eV. Association of these maxima with the corresponding resonant anion states is discussed. The experimentally measured electron detachment times from [AQ](-) as a function of the incident electron energy and the temperature of the target molecule show a pronounced change of slope around 1.5 eV, regardless of the temperature. This unexpected behavior can be qualitatively reproduced within the framework of a multiexponential approach which describes the electron detachment event in terms of a redistribution of the anion excess energy, regardless of the initial mechanism of temporary anion formation. PMID- 20590200 TI - On the assessment of hydroxyapatite fluoridation by means of Raman scattering. AB - Hydroxyapatite is the main mineral component of bones and teeth. Fluorapatite, a bioceramic that can be obtained from hydroxyapatite by chemical substitution of the hydroxide ions with fluoride, exhibits lower mineral solubility and larger mechanical strength. Despite the widespread use of fluoride against caries, a reliable technique for unambiguous assessment of fluoridation in in vitro tests is still lacking. Here we present a method to probe fluorapatite formation in fluoridated hydroxyapatite by combining Raman scattering with thermal annealing. In synthetic minerals, we found that effectively fluoride substituted hydroxyapatite transforms into fluorapatite only after heat treatment, due to the high activation energy for this first order phase transition. PMID- 20590201 TI - Excess entropy scaling of diffusion in room-temperature ionic liquids. AB - Excess entropy scaling relationships for diffusivity of ions in room-temperature ionic liquids are tested using molecular dynamics simulations for a model ionic liquid, dimethyl imidazolium chloride. The thermodynamic excess entropy of the single ions (estimated from the ion-ion pair correlation functions) is shown to be very strongly correlated with the diffusivity. An essential feature of these systems, the fact that the heavier and larger cation has a greater diffusivity with respect to the anion, is correctly captured by the excess entropy calculations, which estimates the diffusivity ratio between the two ions with noticeable precision. PMID- 20590202 TI - Negative and positive ion trapping by isotopic molecules in cryocrystals in case of solid parahydrogen containing electrons and H(6) (+) radical cations. AB - We performed electron spin resonance studies of trapped electrons and H(6) (+) radical cations produced by radiolysis of solid parahydrogen (p-H(2)), p-H(2) ortho-D(2) (o-D(2)), and p-H(2)-HD mixtures. Yields of trapped electrons, H(6) (+) radical cations, and its isotopic analogs H(6-n)D(n) (+) (4>or=n>or=1) increased with increasing o-D(2) and HD concentrations in solid p-H(2). Electrons were found trapped near an o-D(2) or an HD in solid p-H(2) due to the long-range charge-induced dipole and quadrupole interactions between electrons and isotopic hydrogen molecules. H(6) (+) radical cations diffuse in solid p-H(2) by repetition of H(6) (+)+H(2)-->H(2)+H(6) (+) and are trapped by ortho-D(2) or HD to form H(6-n)D(n) (+) (4>or=n>or=1) as isotope condensation reactions. Decay behaviors of these cations by the repetition, isotope condensation, and geminate recombination between electrons and H(6-n)D(n) (+) (4>or=n>or=0) were reproduced by determining the corresponding reaction rate constants k(1), k(2), and k(3). Values of 0.045 and 0.0015 L mol(-1) min(-1) were obtained for k(1) (H(6) (+)+D(2)-->H(2)+H(4)D(2) (+)) and k(2) (H(4)D(2) (+)+D(2)-->H(2)+H(2)D(4) (+)), respectively, and the value was quasinull for k(3) (H(2)D(4) (+)+D(2)-->H(2)+D(6) (+)). These rate constants suggest that hole mobility drastically decreased in the repetition reaction when H(6) (+) radical cations acting as hole carriers formed H(4)D(2) (+) or H(2)D(4) (+). HD and D(2) molecules, therefore, act as electron and hole acceptors in irradiated solid p-H(2)-o-D(2) and p-H(2)-HD mixtures. PMID- 20590203 TI - Ice crystallization in water's "no-man's land". AB - The crystallization of water at 180 K is studied through large-scale molecular dynamics simulations with the monatomic water model mW. This temperature is in the middle of water's "no-man's land," where rapid ice crystallization prevents the elucidation of the structure of liquid water and its transformation into ice with state of the art experimental methods. We find that critical ice nuclei (that contain less than ten water molecules) form in a time scale shorter than the time required for the relaxation of the liquid, suggesting that supercooled liquid water cannot be properly equilibrated in this region. We distinguish three stages in the crystallization of water at 180 K: concurrent nucleation and growth of ice, followed by consolidation that decreases the number density of ice nuclei, and finally, slow growth of the crystallites without change in their number density. The kinetics of the transformation along the three stages is well described by a single compacted exponential Avrami equation with n approximately 1.7. This work confirms the coexistence of ice and liquid after water is crystallized in "no-man's land": the formation of ice plateaus when there is still 15%-20% of liquid water in the systems, thinly dispersed between ice I crystals with linear dimensions ranging from 3 to 10 nm. We speculate that the nanoscopic size of the crystallites decreases their melting point and slows their evolution toward the thermodynamically most stable fully crystalline state. PMID- 20590204 TI - Homogeneous water nucleation in a laminar flow diffusion chamber. AB - Homogeneous nucleation rates of water at temperatures between 240 and 270 K were measured in a laminar flow diffusion chamber at ambient pressure and helium as carrier gas. Being in the range of 10(2)-10(6) cm(-3) s(-1), the experimental results extend the nucleation rate data from literature consistently and fill a pre-existing gap. Using the macroscopic vapor pressure, density, and surface tension for water we calculate the nucleation rates predicted by classic nucleation theory (CNT) and by the empirical correction function of CNT by Wolk and Strey [J. Phys. Chem. B 105, 11683 (2001)]. As in the case of other systems (e.g., alcohols), CNT predicts a stronger temperature dependence than experimentally observed, whereas the agreement with the empirical correction function is good for all data sets. Furthermore, the isothermal nucleation rate curves allow us to determine the experimental critical cluster sizes by use of the nucleation theorem. A comparison with the critical cluster sizes calculated by use of the Gibbs-Thomson equation is remarkably good for small cluster sizes, for bigger ones the Gibbs-Thomson equation overestimates the cluster sizes. PMID- 20590205 TI - Escape of a driven particle from a metastable state: A semiclassical approach. AB - In this article we explore the dynamics of escape of a particle in the semiclassical regime by driving the particle externally. We demonstrate that under suitable approximations the semiclassical escape rate essentially assumes the structure of classical Kramers rate. Both internal (due to thermal bath) as well as external noises (due to driving) are being considered. The noises are stationary, Gaussian, and are characterized by arbitrary decaying memory kernel. Finally, we subject our formulation to rigorous numerical test under variedly changing conditions of the parameters. PMID- 20590206 TI - Quantifying the transfer and settling in NMR experiments with sample shuttling. AB - Nuclear magnetic resonance (NMR) in combination with pulsed magnetic field gradients has proven very successful for measuring molecular diffusion, where the correlation time of the motion is much shorter than the timescale of the experiment. In this article, it is demonstrated that a single-scan NMR technique to measure molecular diffusion can be employed to also study incoherent random motions over macroscopic length scales that show correlation times similar to the timescale of the experiment. Such motions are observed, for example, after the mixing of two components or after transferring a sample from one container into another. To measure the fluid settling, a series of magnetization helices were encoded onto a sample. Stimulated gradient echo trains were then generated after different mixing times, which enabled the determination of an effective dispersion coefficient for the fluid. This technique was used to optimize the timing of NMR experiments combined with dissolution dynamic nuclear polarization, where a sample was shuttled between two magnets. In addition to the decay of fluid turbulences, the presence of microbubbles in the sample tube at the end of the shuttling step was identified as another contribution to the NMR linewidth. Microbubbles could be indirectly observed through the line broadening effect on the NMR signal due to their different susceptibility compared to the solvent, which induced field gradients near the interfaces. Using these data, the signal attenuation caused by sample motion in single-scan two-dimensional correlation spectroscopy NMR experiments could be predicted with reasonable accuracy. PMID- 20590207 TI - Lyapunov spectra and conjugate-pairing rule for confined atomic fluids. AB - In this work we present nonequilibrium molecular dynamics simulation results for the Lyapunov spectra of atomic fluids confined in narrow channels of the order of a few atomic diameters. We show the effect that realistic walls have on the Lyapunov spectra. All the degrees of freedom of the confined system have been considered. Two different types of flow have been simulated: planar Couette flow and planar Poiseuille flow. Several studies exist on the former for homogeneous flows, so a direct comparison with previous results is performed. An important outcome of this work is the demonstration of how the spectrum reflects the presence of two different dynamics in the system: one for the unthermostatted fluid atoms and the other one for the thermostatted and tethered wall atoms. In particular the Lyapunov spectrum of the whole system does not satisfy the conjugate-pairing rule. Two regions are instead distinguishable, one with negative pairs' sum and one with a sum close to zero. To locate the different contributions to the spectrum of the system, we computed "approximate" Lyapunov exponents belonging to the phase space generated by the thermostatted area and the unthermostatted area alone. To achieve this, we evolved Lyapunov vectors projected into a reduced dimensional phase space. We finally observe that the phase-space compression due to the thermostat remains confined into the wall region and does not significantly affect the purely Newtonian fluid region. PMID- 20590208 TI - Initiation of a passivated interface between hafnium oxide and In(Ga)As(0 0 1) (4x2). AB - Hafnium oxide interfaces were studied on two related group III rich semiconductor surfaces, InAs(0 0 1)-(4x2) and In(0.53)Ga(0.47)As(0 0 1)-(4x2), via two different methods: reactive oxidation of deposited Hf metal and electron beam deposition of HfO(2). The interfaces were investigated with scanning tunneling microscopy and spectroscopy (STS). Single Hf atom chemisorption sites were identified that are resistant to oxidation by O(2), but Hf islands are reactive to O(2). After e(-) beam deposition of <<1 ML of HfO(2), single chemisorption sites were identified. At low coverage (<1 ML), the n-type and p-type HfO(2)/InGaAs(0 0 1)-(4x2) interfaces show p-type character in STS, which is typical of clean InGaAs(0 0 1)-(4x2). After annealing below 200 degrees C, full coverage HfO(2)/InGaAs(0 0 1)-(4x2) (1-3 ML) has the surface Fermi level shifted toward the conduction band minimum for n-type InGaAs, but near the valence band maximum for p-type InGaAs. This is consistent with the HfO(2)/InGaAs(0 0 1)-(4x2) interface being at least partially unpinned, i.e., a low density of states in the band gap. The partially unpinned interface results from the modest strength of the bonding between HfO(2) and InGaAs(0 0 1)-(4x2) that prevents substrate atom disruption. The fortuitous structure of HfO(2) on InAs(0 0 1)-(4x2) and InGaAs(0 0 1)-(4x2) allows for the elimination of the partially filled dangling bonds on the surface, which are usually responsible for Fermi level pinning. PMID- 20590209 TI - Theoretical investigation on the chemical sensing of metalloporphyrin-based molecular junction. AB - Following the previous study [N. Wang et al., J. Phys. Chem. C 113, 7416 (2009)] which focused on specific electron transport pathway in the cyclic molecules, we investigated the chemical sensing of the metalloporphyrin-based molecular junctions. Theoretical calculations have been carried out using density functional theory combined with the nonequilibrium Green's function method. The adsorbed molecules (CO, NO, and O(2)) show diverse effects which depend on the connecting position between the metalloporphyrin with the electrodes. For iron (II) porphyrin (FeP) and manganese (II) porphyrin (MnP) connected at the 9,11 position (P-connection), the electron only passes through the porphyrin ring and the binding of ligand has no effect on the molecular conductivity. However, for the FeP and MnP connected at the 1,5-position (D-connection), the molecular conductivity decreases dramatically after adsorptions of three diatomic molecules as a result of the electron takes the path through the metallic center. For the potential application of chemical sensing, the selectivities of the FeP and MnP are discussed as well. PMID- 20590210 TI - Theory of interfacial orientational relaxation spectroscopic observables. AB - The orientational correlation functions measured in the time-resolved second harmonic generation (TRSHG) and time-resolved sum-frequency generation (TRSFG) experiments are derived. In the laboratory coordinate system, the Y(l) (m)(Omega(lab)(t))Y(2) (m)(Omega(lab)(0)) (l=1,3 and m=0,2) correlation functions, where the Y(l) (m) are spherical harmonics, describe the orientational relaxation observables of molecules at interfaces. A wobbling-in-a-cone model is used to evaluate the correlation functions. The theory demonstrates that the orientational relaxation diffusion constant is not directly obtained from an experimental decay time in contrast to the situation for a bulk liquid. Model calculations of the correlation functions are presented to demonstrate how the diffusion constant and cone half-angle affect the time-dependence of the signals in TRSHG and TRSFG experiments. Calculations for the TRSHG experiments on Coumarin C314 molecules at air-water and air-water-surfactant interfaces are presented and used to examine the implications of published experimental results for these systems. PMID- 20590211 TI - Density functional approach to the description of fluids in contact with bilayers. AB - We discuss an application of a density functional approach to describe a bilayer, or a simplified model of a membrane, that is built of tethered chain molecules. The bilayer integrity is maintained by tethering chain particles to two common sheets. We study the structure of a two-component mixture in contact with the bilayer, as well as the solvation force acting between two bilayers, immersed in a fluid. The fluid is a binary mixture involving the component that can cross freely the bilayer and the second impenetrable component. All the calculations are carried out for athermal system, in which only hard-core interactions are present. PMID- 20590212 TI - Obtaining true transverse relaxation time distributions in high-field NMR measurements of saturated porous media: Removing the influence of internal gradients. AB - It is well known that nuclear magnetic resonance (NMR) transverse relaxation measurements of porous media at high magnetic field strengths provide only an effective relaxation time T(2,eff), as opposed to the true T(2), due to molecular diffusion through magnetic field gradients induced by the magnetic susceptibility contrast between the adsorbent and the adsorbate. Here, we deconvolve the diffusion and surface relaxation contributions to measurements of T(2,eff) and thus obtain the true T(2) relaxation time distribution. This technique is applicable within the short time diffusion regime where the diffusion exponent varies as t(E) (3), while the surface relaxation exponent varies as t(E), where t(E) is the echo time in a standard Carr-Purcell Meiboom-Gill measurement. We demonstrate this technique on measurements of water in contact with glass spheres across a range of magnetic field strengths from B(0)=50 mT to 7.4 T. A direct measurement of T(2,eff) suggests that the transverse relaxation rate increases with field strength, in contrast to theoretical predictions. We show that when the effects of the susceptibility induced gradients, which are known to increase with magnetic field strength, are deconvolved from the T(2,eff) measurement, the true T(2) relaxation rate does indeed decrease with increasing field strength. We also apply the T(2) correction in multidimensional NMR experiments using the example of a T(1)-T(2) relaxation correlation. Here, the correction is essential in order to obtain the true T(1)/T(2) ratio as a function of magnetic field strength, which provides a measure of mobility for surface-adsorbed species; without this correction, we see surface residence times overestimated by up to two orders of magnitude. This novel approach enables the accurate determination of T(2) distributions, and hence T(1)/T(2) ratios, on high-field spectrometers that would have previously been deemed inappropriate for the study of liquids in porous media because of the intrinsic susceptibility effects. PMID- 20590213 TI - Thermostating highly confined fluids. AB - In this work we show how different use of thermostating devices and modeling of walls influence the mechanical and dynamical properties of confined nanofluids. We consider a two dimensional fluid undergoing Couette flow using nonequilibrium molecular dynamics simulations. Because the system is highly inhomogeneous, the density shows strong fluctuations across the channel. We compare the dynamics produced by applying a thermostating device directly to the fluid with that obtained when the wall is thermostated, considering also the effects of using rigid walls. This comparison involves an analysis of the chaoticity of the fluid and evaluation of mechanical properties across the channel. We look at two thermostating devices with either rigid or vibrating atomic walls and compare them with a system only thermostated by conduction through vibrating atomic walls. Sensitive changes are observed in the xy component of the pressure tensor, streaming velocity, and density across the pore and the Lyapunov localization of the fluid. We also find that the fluid slip can be significantly reduced by rigid walls. Our results suggest caution in interpreting the results of systems in which fluid atoms are thermostated and/or wall atoms are constrained to be rigid, such as, for example, water inside carbon nanotubes. PMID- 20590214 TI - Dissipative particle dynamics simulations on inversion dynamics of spherical micelles. AB - We simulate the inversion process of a spherical micelle composed of symmetric diblock copolymers by means of dissipative particle dynamics. The evolution of micelle morphology reveals that the inversion is a two-staged process, in which a rapid agglomeration of outer lyophobic blocks occurs first, followed by a slow penetration of inner lyophilic blocks through the porous lyophobic layer. Calculation of the radius of gyration and hydrodynamic radius indicates that an intermediate with a dilute core and a dense shell emerges in the inversion. The characteristic time of inversion scales with the block copolymer chain length with the scaling exponent ranging from 1.67 to 1.89, which can be well described by a simplified chemical-potential-driven flow model. Further simulations incorporating different denaturation times for the two types of blocks indicate the inversions do not experience molecularly scattered states, but form either collapsed intermediates or loosely associated clusters of small sizes. Possible connections of the simulations to the light scattering experiments are discussed. PMID- 20590215 TI - How many atoms are required to characterize accurately trajectory fluctuations of a protein? AB - Large molecules, whose thermal fluctuations sample a complex energy landscape, exhibit motions on an extended range of space and time scales. Principal component analysis (PCA) is often used to extract dominant motions that in proteins are typically domain motions. These motions are captured in the large eigenvalue (leading) principal components. There is also information in the small eigenvalues, arising from approximate linear dependencies among the coordinates. These linear dependencies suggest that instead of using all the atom coordinates to represent a trajectory, it should be possible to use a reduced set of coordinates with little loss in the information captured by the large eigenvalue principal components. In this work, methods that can monitor the correlation (overlap) between a reduced set of atoms and any number of retained principal components are introduced. For application to trajectory data generated by simulations, where the overall translational and rotational motion needs to be eliminated before PCA is carried out, some difficulties with the overlap measures arise and methods are developed to overcome them. The overlap measures are evaluated for a trajectory generated by molecular dynamics for the protein adenylate kinase, which consists of a stable, core domain, and two more mobile domains, referred to as the LID domain and the AMP-binding domain. The use of reduced sets corresponding, for the smallest set, to one-eighth of the alpha carbon (CA) atoms relative to using all the CA atoms is shown to predict the dominant motions of adenylate kinase. The overlap between using all the CA atoms and all the backbone atoms is essentially unity for a sum over PCA modes that effectively capture the exact trajectory. A reduction to a few atoms (three in the LID and three in the AMP-binding domain) shows that at least the first principal component, characterizing a large part of the LID-binding and AMP binding motion, is well described. Based on these results, the overlap criterion should be applicable as a guide to postulating and validating coarse-grained descriptions of generic biomolecular assemblies. PMID- 20590216 TI - Dielectric properties of fully hydrated nucleotides in the terahertz frequency range. AB - We use terahertz time domain spectroscopy (THz-TDS) to determine the complex frequency-dependent dielectric response of all four nucleotides at different dilute concentrations. In addition, the suspension model's ability to extract the dielectric response of just the nucleotide with the hydration shell epsilon(b) excluding the dielectric information relating to the bulk will be verified. The suspension model enables us to make the determination that the nucleotides have influences on the water molecules out to the fourth hydration shell. We use a two Debye relaxation fit model for water, all concentrations and all epsilon(b) values. We observed how the nucleotides affect the relaxation parameters in relation to that of pure bulk water. With this information, we notice a transition between purines and pyrimidines, where one is a hydrogen-bond network structure building type material with a low concentration increment and the other is a structure breaking type material with a low concentration decrement. Due to conductivity measurements, we determine that kinetic depolarization is a negligible affect compared to that of dielectric saturation, which we find to dominate where a decrement is found. PMID- 20590218 TI - Notes on configurational thermostat schemes. PMID- 20590217 TI - How the diffusivity profile reduces the arbitrariness of protein folding free energies. AB - The concept of a protein diffusing in its free-energy folding landscape has been fruitful for both theory and experiment. Yet the choice of the reaction coordinate (RC) introduces an undesirable degree of arbitrariness into the problem. We analyze extensive simulation data of an alpha-helix in explicit water solvent as it stochastically folds and unfolds. The free-energy profiles for different RCs exhibit significant variations, some having an activation barrier, while others not. We show that this variation has little effect on the predicted folding kinetics if the diffusivity profiles are properly taken into account. This kinetic quasi-universality is rationalized by an RC rescaling, which, due to the reparameterization invariance of the Fokker-Planck equation, allows the combination of free-energy and diffusivity effects into a single function, the rescaled free-energy profile. This rescaled free energy indeed shows less variation among different RCs than the bare free energy and diffusivity profiles separately do, if we properly distinguish between RCs that contain knowledge of the native state and those that are purely geometric in nature. Our method for extracting diffusivity profiles is easily applied to experimental single molecule time series data and might help to reconcile conflicts that arise when comparing results from different experimental probes for the same protein. PMID- 20590219 TI - A novel experimental system of high stability and lifetime for the laser desorption of biomolecules. AB - A novel laser desorption system, with improved signal stability and extraordinary long lifetime, is presented for the study of jet-cooled biomolecules in the gas phase using vibrationally resolved photoionization spectroscopy. As a test substance tryptophane is used to characterize this desorption source. A usable lifetime of above 1 month (for a laser desorption repetition rate of 20 Hz) has been observed by optimizing the pellets (graphite/tryptophane, 3 mm diameter and 6 mm length) from which the substance is laser-desorbed. Additionally, the stability and signal-to-noise ratio has been improved by averaging the signal over the entire sample pellet by synchronizing the data acquisition with the rotation of the sample rod. The results demonstrate how a combination of the above helps to produce stable and conclusive spectra of tryptophane using one color and two-color resonant two-photon ionization studies. PMID- 20590220 TI - A quantum cascade laser cw cavity ringdown spectrometer coupled to a supersonic expansion source. AB - A new instrument has been constructed that couples a supersonic expansion source to a continuous wave cavity ringdown spectrometer using a Fabry-Perot quantum cascade laser (QCL). The purpose of the instrument is to enable the acquisition of a cold, rotationally resolved gas phase spectrum of buckminsterfullerene (C(60)). As a first test of the system, high resolution spectra of the nu(8) vibrational band of CH(2)Br(2) have been acquired at approximately 1197 cm(-1). To our knowledge, this is the first time that a vibrational band not previously recorded with rotational resolution has been acquired with a QCL-based ringdown spectrometer. 62 transitions of the three isotopologues of CH(2)Br(2) were assigned and fit to effective Hamiltonians with a standard deviation of 14 MHz, which is smaller than the laser frequency step size. The spectra have a noise equivalent absorption coefficient of 1.4 x 10(-8) cm(-1). Spectral simulations of the band indicate that the supersonic source produces rotationally cold (approximately 7 K) molecules. PMID- 20590221 TI - 85Rb tunable-interaction Bose-Einstein condensate machine. AB - We describe our experimental setup for creating stable Bose-Einstein condensates (BECs) of (85)Rb with tunable interparticle interactions. We use sympathetic cooling with (87)Rb in two stages, initially in a tight Ioffe-Pritchard magnetic trap and subsequently in a weak, large-volume, crossed optical dipole trap, using the 155 G Feshbach resonance to manipulate the elastic and inelastic scattering properties of the (85)Rb atoms. Typical (85)Rb condensates contain 4 x 10(4) atoms with a scattering length of a=+200a(0). Many aspects of the design presented here could be adapted to other dual-species BEC machines, including those involving degenerate Fermi-Bose mixtures. Our minimalist apparatus is well suited to experiments on dual-species and spinor Rb condensates, and has several simplifications over the (85)Rb BEC machine at JILA, which we discuss at the end of this article. PMID- 20590222 TI - Data processing correction of the irising effect of a fast-gating intensified charge-coupled device on laser-pulse-excited luminescence spectra. AB - Intensified charge-coupled devices (ICCDs) comprise the advantages of both fast gating detectors and spectrally broad CCDs into one device that enables temporally and spectrally resolved measurements with a few nanosecond resolution. Gating of the measured signal occurs in the image intensifier tube, where a high voltage is applied between the detector photocathode and a microchannel plate electron multiplier. An issue arises in time-resolved luminescence spectroscopy when signal onset characterization is required. In this case, the transient gate closing process that causes the detected signal always arises in the middle of the ICCD chip regardless of the spectral detection window--the so-called irising effect. We demonstrate that in case when the detection gate width is comparable to the opening/closing time and the gate is pretriggered with respect to the signal onset, the irising effect causes the obtained data to be strongly distorted. At the same time, we propose a software procedure that leads to the spectral correction of the irising effect and demonstrate its validity on the distorted data. PMID- 20590223 TI - A 12.5 GHz-spaced optical frequency comb spanning >400 nm for near-infrared astronomical spectrograph calibration. AB - A 12.5 GHz-spaced optical frequency comb locked to a global positioning system disciplined oscillator for near-infrared (IR) spectrograph calibration is presented. The comb is generated via filtering a 250 MHz-spaced comb. Subsequent nonlinear broadening of the 12.5 GHz comb extends the wavelength range to cover 1380-1820 nm, providing complete coverage over the H-band transmission window of earth's atmosphere. Finite suppression of spurious sidemodes, optical linewidth, and instability of the comb has been examined to estimate potential wavelength biases in spectrograph calibration. Sidemode suppression varies between 20 and 45 dB, and the optical linewidth is approximately 350 kHz at 1550 nm. The comb frequency uncertainty is bounded by +/-30 kHz (corresponding to a radial velocity of +/-5 cm/s), limited by the global positioning system disciplined oscillator reference. These results indicate that this comb can readily support radial velocity measurements below 1 m/s in the near IR. PMID- 20590224 TI - Generation of tunable narrow bandwidth nanosecond pulses in the deep ultraviolet for efficient optical pumping and high resolution spectroscopy. AB - Nanosecond optical pulses with high power and spectral brightness in the deep ultraviolet (UV) region have been produced by sum frequency mixing of nearly transform-limited-bandwidth IR light originating from a home-built injection seeded ring cavity KTiOPO(4) optical parametric oscillator (OPO) and the fourth harmonic beam of an injection-seeded Nd:YAG laser used simultaneously to pump the OPO with the second harmonic. We demonstrate UV output, tunable from 204 to 207 nm, which exhibits pulse energies up to 5 mJ with a bandwidth better than 0.01 cm(-1). We describe how the approach shown in this paper can be extended to wavelengths shorter than 185 nm. The injection-seeded OPO provides high conversion efficiency (>40% overall energy conversion) and superior beam quality required for highly efficient downstream mixing where sum frequencies are generated in the UV. The frequency stability of the system is excellent, making it highly suitable for optical pumping. We demonstrate high resolution spectroscopy as well as optical pumping using laser-induced fluorescence and stimulated emission pumping, respectively, in supersonic pulsed molecular beams of nitric oxide. PMID- 20590225 TI - Double conical crystal x-ray spectrometer for high resolution ultrafast x-ray absorption near-edge spectroscopy of Al K edge. AB - An x-ray spectrometer devoted to dynamical studies of transient systems using the x-ray absorption fine spectroscopy technique is presented in this article. Using an ultrafast laser-induced x-ray source, this optical device based on a set of two potassium acid phthalate conical crystals allows the extraction of x-ray absorption near-edge spectroscopy structures following the Al absorption K edge. The proposed experimental protocol leads to a measurement of the absorption spectra free from any crystal reflectivity defaults and shot-to-shot x-ray spectral fluctuation. According to the detailed analysis of the experimental results, a spectral resolution of 0.7 eV rms and relative fluctuation lower than 1% rms are achieved, demonstrated to be limited by the statistics of photon counting on the x-ray detector. PMID- 20590226 TI - A new spectroscopic method for resolving the electronic symmetry properties of the highly excited molecules produced in photoexcitation. AB - A novel method of spectroscopy for highly excited states of molecules in the valence excitation range has been established through the detection of metastable hydrogen atoms in the 2s state formed by photoexcitation. The detector for the metastable hydrogen atom is composed of a stack of parallel plate electrodes that creates a localized electric field and triggers the emission of the Lyman-alpha photon from the atom and a chevron pair of microchannel plates that detects the photon. For linear molecules, the angle-resolved detection of the metastable hydrogen atom enables us to measure cross sections in which electronic symmetries of highly excited molecular states are resolved. Such symmetry-resolved cross section measurements were carried out for doubly excited states of H(2). PMID- 20590227 TI - Nanograting-based compact vacuum ultraviolet spectrometer and beam profiler for in situ characterization of high-order harmonic generation light sources. AB - A compact, versatile device for vacuum ultraviolet (VUV) beam characterization is presented. It combines the functionalities of a VUV spectrometer and a VUV beam profiler in one unit and is entirely supported by a standard DN200 CF flange. The spectrometer employs a silicon nitride transmission nanograting in combination with a microchannel plate-based imaging detector. This enables the simultaneous recording of wavelengths ranging from 10 to 80 nm with a resolution of 0.25-0.13 nm. Spatial beam profiles with diameters up to 10 mm are imaged with 0.1 mm resolution. The setup is equipped with an in-vacuum translation stage that allows for in situ switching between the spectrometer and beam profiler modes and for moving the setup out of the beam. The simple, robust design of the device is well suited for nonintrusive routine characterization of emerging laboratory- and accelerator-based VUV light sources. Operation of the device is demonstrated by characterizing the output of a femtosecond high-order harmonic generation light source. PMID- 20590228 TI - Development of a multiplex fast-scan system for ultrafast time-resolved spectroscopy. AB - A fast-scan method was developed to obtain time-resolved signals with femtosecond resolution over a picosecond range on the fly and in real time. Traditional fast scan methods collect data at each probe wavelength one by one, which is time consuming and thus not possible for the study of photofragile materials. In this work, we have developed a system that performs fast scans with multiplex detection. Ultrafast time-resolved spectroscopy was demonstrated using the newly developed system. Femtosecond laser pulses have been used for pump-probe studies of ultrafast processes in various materials, and both electronic relaxation and vibrational dynamics have been studied. However, experiments have been limited in sensitivity and reliability because they are affected by the long-term instability of the ultrashort laser pulses and by the fragility of the samples. The instability of the sources hinders precise determination of electronic decay dynamics and introduces systematic errors. The fragility of the samples reduces their amount or concentration, and can lead to contamination of the materials even if they were pure before the measurement. These effects make it difficult to obtain reproducible and reliable experimental data. In the present work, we have developed a fast-scan pump-probe spectroscopic system that can complete a set of measurements in less than 2 min. Quantitative estimates of the signal reproducibility demonstrate that these measurements provide higher reproducibility and reliability than conventional measurements. PMID- 20590229 TI - Sample cells for probing solid/liquid interfaces with broadband sum-frequency generation spectroscopy. AB - Two sample cells designed specifically for sum-frequency-generation (SFG) measurements at the solid/liquid interface were developed: one thin-layer analysis cell allowing measurement of films on reflective metallic surfaces through a micrometer layer of solution and one spectroelectrochemical cell allowing investigation of processes at the indium tin oxide/solution interface. Both sample cells are described in detail and data illustrating the capabilities of each are shown. To further improve measurements at solid/liquid interfaces, the broadband SFG system was modified to include a reference beam which can be measured simultaneously with the sample signal, permitting background correction of SFG spectra in real time. Sensitivity tests of this system yielded a signal-to noise ratio of 100 at a surface coverage of 0.2 molecules/nm(2). Details on data analysis routines, pulse shaping methods of the visible beam, as well as the design of a purging chamber and sample stage setup are presented. These descriptions will be useful to those planning to set up a SFG spectrometer or seeking to optimize their own SFG systems for measurements of solid/liquid interfaces. PMID- 20590230 TI - A rotatable electron spectrometer for multicoincidence experiments. AB - We have developed a rotatable hemispherical spectrometer with good energy and angular resolution, which can be positioned with the lens axis arbitrarily within a solid angle of 1 pi. The collection angle of the emitted electrons with respect to the polarization axis of the light is set by means of a three-axes goniometer, operating under vacuum. An important requirement for this setup was the possibility to perform coincidences between the electron analyzed by the spectrometer and one or several other particles, such as ions, electrons, or photons. The lens system and the hemispheres have been designed to accommodate such experimental demands, regarding parameters such as the resolving power, the acceptance angle, or the width of the kinetic energy window which can be recorded for a given pass energy. We have chosen to detect the impact position of the electron at the focal plane of the hemispherical analyzer with a delay line detector and a time-to-digital converter as acquisition card rather than using a conventional charge-coupled device camera. PMID- 20590231 TI - Absolute detection efficiencies of a microchannel plate detector for 0.5-5 keV neutrals. AB - The absolute detection efficiencies of a microchannel plate detector for neutral atoms were measured using the coincidence method for neutralized incident ions and ionized target atoms in electron capture collisions. This method does not require knowledge of the absolute electron-capture rates for determination of the detection efficiencies. Results for Ne, Ar, and Kr atoms at energies of 0.5-5 keV are reported. The detection efficiencies for all atomic species increase concomitantly with increasing impact energy and plateau at the efficiency of about 50%. For low impact energies, the efficiency decreases with increasing mass of the impact atom at a given energy. PMID- 20590232 TI - Pulsed ion extraction diagnostics in a quadrupole ion trap linear time-of-flight mass spectrometer. AB - Pulsed extraction techniques are investigated for a quadrupole ion trap (QIT) interfaced to a linear time-of-flight (TOF) mass analyzer. A nonfocusing short pulse mode of operation is developed and characterized. The short-pulse mode creates a near-monoenergetic ion packet, which is useful for reaction kinetics experiments and for making diagnostic measurements of the ion cloud size in the trap. Monopolar and bipolar pulsing modes, with the voltage pulses applied to one or both QIT endcaps to extract the ions into the TOF region, are compared. Ion TOF peak distributions are characterized experimentally and by ion trajectory simulations. Also, first-order spatial (Wiley-McLaren) focusing of ions is characterized for the conventional long-pulse extraction mode. The nonparallel fields in the QIT, which serves as the first acceleration region in the linear TOF mass spectrometer, are shown to degrade spatial focusing and mass resolution. PMID- 20590233 TI - Study of the reflectivity of neutron supermirrors influenced by surface oil layers. AB - Neutron guides made of supermirror-coated glass are important components of most neutron scattering instruments, thus their quality and possible deterioration due to various deleterious effects (e.g., surface contamination or defects) deserve careful examination. The modification of the reflectivity of supermirrors and the transmission of neutron guides due to surface contamination with hydrocarbon oil has been investigated using neutron reflectometry together with model calculations. A significant loss in the neutron reflectivity was observed for supermirrors covered with thin hydrocarbon oil films, which were confirmed in model calculations. Simulations carried out for several typical arrangements show drastic decreases in the transmitted neutron flux of neutron guides. These simulations show that determining the distortion of the beam profile (using a slit or a pin hole) enables the detection of oil contamination even in an operating neutron guide. PMID- 20590234 TI - A simple double-focusing electrostatic ion beam deflector. AB - We have developed an electrostatic, double-focusing 90 degrees deflector for fast ion beams consisting of concentric cylindrical plates of differing heights. In contrast to standard cylindrical deflectors, our design allows for focusing of an incoming parallel beam not only in the plane of deflection but also in the orthogonal direction. The optical properties of our design resemble those of a spherical capacitor deflector while it is much easier and more cost effective to manufacture. PMID- 20590235 TI - First results obtained from the soft x-ray pulse height analyzer on experimental advanced superconducting tokamak. AB - An assembly of soft x-ray pulse height analyzer system, based on silicon drift detector (SDD), has been successfully established on the experimental advanced superconducting tokamak (EAST) to measure the spectrum of soft x-ray emission (E=1-20 keV). The system, including one 15-channel SDD linear array, is installed on EAST horizontal port C. The time-resolved radial profiles of electron temperature and K(alpha) intensities of metallic impurities have been obtained with a spatial resolution of around 7 cm during a single discharge. It was found that the electron temperatures derived from the system are in good agreement with the values from Thomson scattering measurements. The system can also be applied to the measurement of the long pulse discharge for EAST. The diagnostic system is introduced and some typical experimental results obtained from the system are also presented. PMID- 20590236 TI - Diagnostics for first plasma and development plan on KSTAR. AB - The first plasma with target values of the plasma current and the pulse duration was finally achieved on June 13, 2008 in the Korea Superconducting Tokamak Advanced Research (KSTAR). The diagnostic systems played an important role in achieving successful first plasma operation for the KSTAR tokamak. The employed plasma diagnostic systems for the KSTAR first plasma including the magnetic diagnostics, millimeter-wave interferometer, inspection illuminator, H(alpha), visible spectrometer, filterscope, and electron cyclotron emission (ECE) radiometer have provided the main plasma parameters, which are essential for the plasma generation, control, and physics understanding. Improvements to the first diagnostic systems and additional diagnostics including an x-ray imaging crystal spectrometer, reflectometer, ECE radiometer, resistive bolometer, and soft x-ray array are scheduled to be added for the next KSTAR experimental campaign in 2009. PMID- 20590237 TI - Electrostatic diagnostics of nanosecond pulsed electron beams in a Malmberg Penning trap. AB - A fast electrostatic diagnostic and analysis scheme on nanosecond pulsed beams in the keV energy range has been developed in the Malmberg-Penning trap ELTRAP. Low noise electronics has been used for the detection of small induced current signals on the trap electrodes. A discrete wavelet-based procedure has been implemented for data postprocessing. The development of an effective electrostatic diagnostics together with proper data analysis techniques is of general interest in view of deducing the beam properties through comparison of the postprocessed data with the theoretically computed signal shape, which contains beam radius, length, and average density as fit parameters. PMID- 20590238 TI - Evaluation of ion collection area in Faraday probes. AB - A Faraday probe with three concentric rings was designed and fabricated to assess the effect of gap width and collector diameter in a systematic study of the diagnostic ion collection area. The nested Faraday probe consisted of two concentric collector rings and an outer guard ring, which enabled simultaneous current density measurements on the inner and outer collectors. Two versions of the outer collector were fabricated to create gaps of 0.5 and 1.5 mm between the rings. Distribution of current density in the plume of a low-power Hall thruster ion source was measured in azimuthal sweeps at constant radius from 8 to 20 thruster diameters downstream of the exit plane with variation in facility background pressure. A new analytical technique is proposed to account for ions collected in the gap between the Faraday probe collector and guard ring. This method is shown to exhibit excellent agreement between all nested Faraday probe configurations, and to reduce the magnitude of integrated ion beam current to levels consistent with Hall thruster performance analyses. The technique is further studied by varying the guard ring bias potential with a fixed collector bias potential, thereby controlling ion collection in the gap. Results are in agreement with predictions based on the proposed analytical technique. The method is applied to a past study comparing the measured ion current density profiles of two Faraday probe designs. These findings provide new insight into the nature of ion collection in Faraday probe diagnostics, and lead to improved accuracy with a significant reduction in measurement uncertainty. PMID- 20590239 TI - Spectroscopic interpretation and velocimetry analysis of fluctuations in a cylindrical plasma recorded by a fast camera. AB - Fast visible imaging is used on a cylindrical magnetized argon plasma produced by thermionic discharge in the Mirabelle device. To link the information collected with the camera to a physical quantity, fast camera movies of plasma structures are compared to Langmuir probe measurements. High correlation is found between light fluctuations and plasma density fluctuations. Contributions from neutral argon and ionized argon to the overall light intensity are separated by using interference filters and a light intensifier. Light emitting transitions are shown to involve a metastable neutral argon state that can be excited by thermal plasma electrons, thus explaining the good correlation between light and density fluctuations. The propagation velocity of plasma structures is calculated by adapting velocimetry methods to the fast camera movies. The resulting estimates of instantaneous propagation velocity are in agreement with former experiments. The computation of mean velocities is discussed. PMID- 20590240 TI - Imaging dislocations in gallium nitride across broad areas using atomic force microscopy. AB - We have employed an atomic force microscope with a high sampling rate to image GaN samples grown using an epitaxial layer overgrowth technique and treated with silane and ammonia to enlarge the surface pits associated with threading dislocations (TDs). This allows TDs to be identified in high pixel density images tens of microns in size providing detailed information about the spatial distribution of the TDs. An automated software tool has been developed, which identifies the coordinates of the TDs in the image. Additionally, we have imaged the same sample using Kelvin probe force microscopy, again at high pixel density, providing data about the local changes in surface potential associated with hundreds of dislocations. PMID- 20590241 TI - A compact, sample-in-atmospheric-pressure soft x-ray microscope developed at Pohang Light Source. AB - A full-field transmission soft x-ray microscope (TXM) was developed at the Pohang Light Source. With a 2 mm diameter condenser zone plate and a 40 nm outermost zone-width objective zone plate, the TXM's achieved spatial resolution is better than 50 nm at the photon energy of 500 eV (wavelength: 2.49 nm). The TXM is portable and mounted in tandem with a 7B1 spectroscopy end station. The sample position is outside the vacuum, allowing for quick sample changes and enhanced in situ experimental capability. In addition, the TXM is pinhole-free and easy to align, having commercial mounts located outside the vacuum components. PMID- 20590242 TI - Correction of the viscous drag induced errors in macromolecular manipulation experiments using atomic force microscope. AB - We describe a method to correct the errors induced by viscous drag on the cantilever in macromolecular manipulation experiments using the atomic force microscope. The cantilever experiences a viscous drag force in these experiments because of its motion relative to the surrounding liquid. This viscous force superimposes onto the force generated by the macromolecule under study, causing ambiguity in the experimental data. To remove this artifact, we analyzed the motions of the cantilever and the liquid in macromolecular manipulation experiments, and developed a novel model to treat the viscous drag on the cantilever as the superposition of the viscous force on a static cantilever in a moving liquid and that on a bending cantilever in a static liquid. The viscous force was measured under both conditions and the results were used to correct the viscous drag induced errors from the experimental data. The method will be useful for many other cantilever based techniques, especially when high viscosity and high cantilever speed are involved. PMID- 20590243 TI - Error analysis of the residence time of bistable Poisson states obtained by periodic measurements. AB - We performed error analysis on the periodic measurement schemes to obtain the residence time of bistable Poisson states. Experimental data were obtained by periodical level-sensitive samplings of oxygen-induced states on Si(111)-7 x 7 that stochastically switches between two metastable states. Simulated data sequences were created by the Monte Carlo numerical method. The residence times were extracted from the experimental and simulation data sequences by averaging and exponential-fitting methods. The averaging method yields the residence time via the summation of the detected temporal width of each state weighed by the normalized frequency of the state and the exponential fitting via fitting a single exponential function to the frequency histogram of the data. It is found that the averaging method produces consistently more accurate results with no arbitrariness, when compared to the exponential fitting method. For further understanding, data modeling using the first-order approximation was performed; the enhanced accuracy in the averaging method is due to the mutual cancellation of errors associated with detection of zero-width states and long-tail states. We investigated a multi-interval detection scheme as well. Similar analysis shows that the dual-interval scheme produces larger error compared to the single interval one, and has narrower optimum region. PMID- 20590244 TI - Localization and preparation of recombination-active extended defects for transmission electron microscopy analysis. AB - Recombination-active extended defects in semiconductors frequently occur at a low density which makes their structural and chemical analysis by transmission electron microscopy (TEM) techniques virtually impossible. Here an approach is described that uses in situ electron beam induced current (EBIC) in a focused ion beam machine to localize such defects for TEM lamella preparation. As an example, a defect complex occurring in block-cast multicrystalline silicon with a density of less than 10(4) cm(-3) has been prepared and analyzed by TEM. The chemical sensitivity of the technique is estimated to be about 10(13) atoms cm(-2) which is comparable to synchrotron-based x-ray techniques. The localization accuracy of the TEM lamella is shown to be better than 50 nm when low-energy EBIC is used. PMID- 20590245 TI - Implementation and characterization of a quartz tuning fork based probe consisted of discrete resonators for dynamic mode atomic force microscopy. AB - The quartz tuning fork based probe {e.g., Akiyama et al. [Appl. Surf. Sci. 210, 18 (2003)]}, termed "A-Probe," is a self-sensing and self-actuating (exciting) probe for dynamic mode atomic force microscope (AFM) operation. It is an oscillatory force sensor consisting of the two discrete resonators. This paper presents the investigations on an improved A-Probe: its batch fabrication and assembly, mounting on an AFM head, electrical setup, characterization, and AFM imaging. The fundamental features of the A-Probe are electrically and optically characterized in "approach-withdraw" experiments. Further investigations include the frequency response of an A-Probe to small mechanical vibrations externally applied to the tip and the effective loading force yielding between the tip and the sample during the periodic contact. Imaging of an electronic chip, a compact disk stamper, carbon nanotubes, and Si beads is demonstrated with this probe at ambient conditions in the so-called frequency modulation mode. A special probe substrate, which can snap on a receptacle fixed on an AFM head, and a special holder including a preamplifier electronic are introduced. We hope that the implementation and characterization of the A-Probe described in this paper will provide hints for new scanning probe techniques. PMID- 20590246 TI - A study on axial and torsional resonant mode matching for a mechanical system with complex nonlinear geometries. AB - Making use of mechanical resonance has many benefits for the design of microscale devices. A key to successfully incorporating this phenomenon in the design of a device is to understand how the resonant frequencies of interest are affected by changes to the geometric parameters of the design. For simple geometric shapes, this is quite easy, but for complex nonlinear designs, it becomes significantly more complex. In this paper, two novel modeling techniques are demonstrated to extract the axial and torsional resonant frequencies of a complex nonlinear geometry. The first decomposes the complex geometry into easy to model components, while the second uses scaling techniques combined with the finite element method. Both models overcome problems associated with using current analytical methods as design tools, and enable a full investigation of how changes in the geometric parameters affect the resonant frequencies of interest. The benefit of such models is then demonstrated through their use in the design of a prototype piezoelectric ultrasonic resonant micromotor which has improved performance characteristics over previous prototypes. PMID- 20590247 TI - Magnetotransport properties of high quality Co:ZnO and Mn:ZnO single crystal pulsed laser deposition films: pitfalls associated with magnetotransport on high resistivity materials. AB - The electrical resistivity values for a series of pure and doped (Co, Mn, Al) ZnO epitaxial films grown by pulsed laser deposition were measured with equipment designed for determining the direct current resistivity of high resistance samples. Room-temperature resistances ranging from 7 x 10(1) to 4 x 10(8) Omega/sq were measured on vacuum-reduced cobalt-doped ZnO, (Al,Co) co-doped ZnO, pure cobalt-doped ZnO, Mn-doped ZnO, and undoped ZnO. Using a four-point collinear geometry with gold spring-loaded contacts, resistivities were measured from 295 to 5 K for resistances of < approximately 10(12) Omega/sq. In addition, magnetoresistance and Hall effect were measured as a function of temperature for select samples. Throughout the investigation, samples were also measured on commercially available instrumentation with good agreement. The challenges of transport measurements on high resistivity samples are discussed, along with some offered solutions to those challenges. PMID- 20590248 TI - Design, implementation, and testing of a cryogenic loading capability on an engineering neutron diffractometer. AB - A novel capability was designed, implemented, and tested for in situ neutron diffraction measurements during loading at cryogenic temperatures on the spectrometer for materials research at temperature and stress at Los Alamos National Laboratory. This capability allowed for the application of dynamic compressive forces of up to 250 kN on standard samples controlled at temperatures between 300 and 90 K. The approach comprised of cooling thermally isolated compression platens that in turn conductively cooled the sample in an aluminum vacuum chamber which was nominally transparent to the incident and diffracted neutrons. The cooling/heat rate and final temperature were controlled by regulating the flow of liquid nitrogen in channels inside the platens that were connected through bellows to the mechanical actuator of the load frame and by heaters placed on the platens. Various performance parameters of this system are reported here. The system was used to investigate deformation in Ni-Ti-Fe shape memory alloys at cryogenic temperatures and preliminary results are presented. PMID- 20590249 TI - Design and construction of a novel tribometer with online topography and wear measurement. AB - We present a novel experimental platform that links topographical and material changes with the friction and wear behavior of oil-lubricated metal surfaces. This concept combines state-of-the-art methods for the analysis of the surface topography on the micro- and nanoscale with the online measurement of wear. At the same time, it allows for frictional and lateral force detection. Information on the topography of one of the two surfaces is gathered in situ with a three dimensional (3D) holography microscope at a maximum frequency of 15 frames/s and higher resolution images are provided at defined time intervals by an atomic force microscope. The wear measurement is conducted online by means of radio nuclide technique. The quantitative measurement of the lateral and frictional forces is conducted with a custom-built 3D force sensor. The surfaces can be lubricated with an optically transparent oil or water. The stability and precision of the setup have been tested in a model experiment. The results show that the exact same position can be relocated and examined after each load cycle. Wear and topography measurements were performed with a radioactive labeled iron pin sliding against an iron plate. PMID- 20590250 TI - Efficient fabrication of wafer scale thin film of individualized single-walled carbon nanotubes by dual-nozzle spin casting. AB - In this paper, a dual-nozzle spin casting method was proposed to form a thin film of individualized single-walled carbon nanotubes (SWNTs) at the wafer scale. Each nozzle simultaneously ejected the SWNT solution and methanol, respectively. During the ejection process, two solutions were mixed at the contacting end of the nozzles and then dropped onto the substrate. Functionalization of the wafer substrate with the amine group improved the uniformity of the SWNT thin film as well as the adhesion between the individualized SWNTs and the substrate. The best condition of the spin casting involved the substrate functionalization using 3 aminopropyltriethosilane aqueous solution with a concentration of approximately 10 mM and a deposition velocity of approximately 5000 rpm. The root-mean-square roughness of the fabricated SWNT layer over the wafer substrate was found to be 1.4-1.8 nm, which indicated that the resultant thin film was one or two layers of SWNTs. The wafer scale SWNT thin film formed by dual-nozzle spin casting can be further used for the mass production and high integration of the SWNT nanoelectronic devices. PMID- 20590251 TI - Simultaneous velocity and pressure measurements using luminescent microspheres. AB - Using the technique of modified rapid lifetime determination, pressure-sensitive microspheres, known as PrSBeads, were used to make quantitative oxygen measurements over two-dimensional areas within gaseous flows. Aerosolized PrSBeads in carrier gases of varying oxygen concentrations demonstrated point measurement precisions on the order of 0.1%-1%. A charge-coupled device featuring a double image frame (DIF) feature was used to make spatially resolved pressure measurements within gas phase flows. Errors on the order of 0.5 atm for one standard deviation were demonstrated when 2 x 2 pixel binning (162 x 128 pixel overall resolution) was used, but improved to 0.003-0.005 atm with the use of 32 x 32 pixel binning (10 x 8 pixel overall resolution). Experiments demonstrate the ability to resolve the oxygen concentration differences between a N(2) jet and the surrounding ambient air environment and the ability to measure instantaneous air pressure changes within a square syringe as the plunger is moved in and out. In addition, instantaneous velocity measurements of the airborne PrSBeads in a square syringe were achieved using digital particle image velocimetry at frame rates of 6.4 Hz, thus validating PrSBeads as a tool to simultaneously measure the velocity and pressure within an aerodynamic flow. PMID- 20590252 TI - Reactor for in situ measurements of spatially resolved kinetic data in heterogeneous catalysis. AB - The present work describes a reactor that allows in situ measurements of spatially resolved kinetic data in heterogeneous catalysis. The reactor design allows measurements up to temperatures of 1300 degrees C and 45 bar pressure, i.e., conditions of industrial relevance. The reactor involves reactants flowing through a solid catalyst bed containing a sampling capillary with a side sampling orifice through which a small fraction of the reacting fluid (gas or liquid) is transferred into an analytical device (e.g., mass spectrometer, gas chromatograph, high pressure liquid chromatograph) for quantitative analysis. The sampling capillary can be moved with microm resolution in or against flow direction to measure species profiles through the catalyst bed. Rotation of the sampling capillary allows averaging over several scan lines. The position of the sampling orifice is such that the capillary channel through the catalyst bed remains always occupied by the capillary preventing flow disturbance and fluid bypassing. The second function of the sampling capillary is to provide a well which can accommodate temperature probes such as a thermocouple or a pyrometer fiber. If a thermocouple is inserted in the sampling capillary and aligned with the sampling orifice fluid temperature profiles can be measured. A pyrometer fiber can be used to measure the temperature profile of the solid catalyst bed. Spatial profile measurements are demonstrated for methane oxidation on Pt and methane oxidative coupling on Li/MgO, both catalysts supported on reticulated alpha-Al(2)O(3) foam supports. PMID- 20590253 TI - Automated high pressure cell for pressure jump x-ray diffraction. AB - A high pressure cell for small and wide-angle x-ray diffraction measurements of soft condensed matter samples has been developed, incorporating a fully automated pressure generating network. The system allows both static and pressure jump measurements in the range of 0.1-500 MPa. Pressure jumps can be performed as quickly as 5 ms, both with increasing and decreasing pressures. Pressure is generated by a motorized high pressure pump, and the system is controlled remotely via a graphical user interface to allow operation by a broad user base, many of whom may have little previous experience of high pressure technology. Samples are loaded through a dedicated port allowing the x-ray windows to remain in place throughout an experiment; this facilitates accurate subtraction of background scattering. The system has been designed specifically for use at beamline I22 at the Diamond Light Source, United Kingdom, and has been fully integrated with the I22 beamline control systems. PMID- 20590254 TI - A compact electroencephalogram recording device with integrated audio stimulation system. AB - A compact (96 x 128 x 32 mm(3), 374 g), battery-powered, eight-channel electroencephalogram recording device with an integrated audio stimulation system and a wireless interface is presented. The recording device is capable of producing high-quality data, while the operating time is also reasonable for evoked potential studies. The effective measurement resolution is about 4 nV at 200 Hz sample rate, typical noise level is below 0.7 microV(rms) at 0.16-70 Hz, and the estimated operating time is 1.5 h. An embedded audio decoder circuit reads and plays wave sound files stored on a memory card. The activities are controlled by an 8 bit main control unit which allows accurate timing of the stimuli. The interstimulus interval jitter measured is less than 1 ms. Wireless communication is made through bluetooth and the data recorded are transmitted to an external personal computer (PC) interface in real time. The PC interface is implemented with LABVIEW and in addition to data acquisition it also allows online signal processing, data storage, and control of measurement activities such as contact impedance measurement, for example. The practical application of the device is demonstrated in mismatch negativity experiment with three test subjects. PMID- 20590255 TI - Measurement of ac conductivity of gold nanofilms at microwave frequencies. AB - We proposed an application of the open-terminal method to measure the alternating current (ac) conductivity of metallic nanometer thick films at microwave frequencies. An explicit expression of the conductivity as a function of reflection has been derived. Using the application, we experimentally measured the complex conductivity of gold nanometer films in microwave X band. The results are in good agreement with those obtained by other techniques. We find that the film's surface morphology affects not only the magnitude but also the frequency dependence of the ac conductivity. In some cases, the direct current conductivity can be lower than the ac conductivity deviating from the Drude model, which can be well qualitatively explained by a circuit model for the granular films. PMID- 20590256 TI - Precise phase synchronization of a cryogenic microwave oscillator. AB - We developed a novel technique for accurate phase synchronization of microwave oscillators based on sapphire dielectric resonators cooled to liquid nitrogen temperature. The achieved quality of phase synchronization (a few milliradians) enables the accurate measurements of extremely weak phase fluctuations expected from the next generation of ultralow phase noise microwave oscillators. PMID- 20590257 TI - The detection of electron-beam-induced current in junctionless semiconductor. AB - The scanning electron microscope is a versatile tool and its electron beam techniques have been widely used in semiconductor material and device characterizations. One of these electron beam techniques is the electron-beam induced current (EBIC) technique. One of the limitations of the conventional EBIC technique is that it requires charge collecting junctions which may not be readily available in junctionless samples such as bare substrates unless some special sample preparation procedure such as the fabrication of a diffused junction is done on the junctionless sample. In this paper, the technique of detecting EBIC current in junctionless samples with the use of a two-point probe is presented. It is found that the EBIC current is independent from its physical parameter when the sample thickness is greater than 4L; the width to the right of probe 2 and the width to the left of probe 1 are greater than 2L and 8L, respectively. The parameters affecting this technique of detecting the EBIC current such as the depth of the generation volume, probe spacing, and the applied bias are also discussed in this paper. A commercially available two dimensional device simulator was used to verify this technique. PMID- 20590258 TI - Complex permittivity measurements using cavity perturbation technique with substrate integrated waveguide cavities. AB - Cavity perturbation technique is widely used in the measurements of complex dielectric permittivity of materials due to its accuracy and ease of configuration. This paper presents the theoretical formulas for the evaluation of complex permittivity of materials using cavity perturbation technique with substrate integrated cavity resonators. With the proposed formulas, the use of various planar cavities is possible by taking into account the dielectric characteristics of the substrate in which the cavity is implemented. Simulations and measurements are performed on various dielectric samples to validate the proposed theory. The maximum deviation in the measured dielectric permittivity values is below 6% compared to the literature values. The implemented substrate integrated cavity is then analyzed in terms of sensitivity, showing a good performance. PMID- 20590259 TI - 20 T portable bipolar magnetic pulser. AB - High magnetic fields are required for the study of hard magnetic materials and, in many cases, the reversal of these fields is essential. This paper describes a portable pulse generator capable of producing bipolar magnetic fields up to 20 T into a copper coil. The peak current around 7 kA is achieved by discharging two capacitor banks through a combination of thyristors and fast diodes. Each pulse polarity has a semisinusoidal shape with 18 mus base width. Pulse triggering is computer controlled and magnetic measurements are done by an induction coil or Kerr effect acquired by a sampling oscilloscope. The whole apparatus weighs less than 2 kg. Hysteresis loops of NdFeB magnets were done to demonstrate the viability of the system. PMID- 20590260 TI - A battery-based, low-noise voltage source. AB - A highly stable, low-noise voltage source was designed to improve the stability of the electrode bias voltages of a Penning trap. To avoid excess noise and ground loops, the voltage source is completely independent of the public electric network and uses a 12 V car battery to generate output voltages of +/-15 and +/-5 V. First, the dc supply voltage is converted into ac-voltage and gets amplified. Afterwards, the signal is rectified, filtered, and regulated to the desired output value. Each channel can deliver up to 1.5 A. The current as well as the battery voltage and the output voltages can be read out via a universal serial bus (USB) connection for monitoring purposes. With the presented design, a relative voltage stability of 7 x 10(-7) over 6.5 h and a noise level equal or smaller than 30 nV/square root(Hz) is achieved. PMID- 20590261 TI - Frequency stabilization of a radio frequency excited CO2 laser using the photoacoustic effect. AB - A frequency and a power of rf excited CO(2) laser are stabilized using the photoacoustic effect generated from the laser itself. As the radiation intensity in a laser resonator changed, the pressure of laser medium gas changed due to its photoacoustic effect. A condenser microphone built in the resonator is used to convert delicate variations in the pressure into voltage signals to be used as input signals for lock-in stabilizer. As a result of stabilizing the frequency and power of the laser oscillated from P(20) line, at the apex of gain curve, the relative stability of the optical frequency and the rate of change in laser power are 5.57 x 10(-8) and 9.3%, respectively. PMID- 20590262 TI - Standard photoacoustic spectrometer: model and validation using O2 A-band spectra. AB - We model and measure the absolute response of an intensity-modulated photoacoustic spectrometer comprising a 10 cm long resonator and having a Q factor of approximately 30. We present a detailed theoretical analysis of the system and predict its response as a function of gas properties, resonance frequency, and sample energy transfer relaxation rates. We use a low-power continuous wave laser to probe O(2) A-band absorption transitions using atmospheric, humidified air as the sample gas to calibrate the system. This approach provides a convenient and well-characterized method for calibrating the absolute response of the system provided that water-vapor-mediated relaxation effects are properly taken into account. We show that for photoacoustic spectroscopy (PAS) of the O(2) A-band, the maximum conversion efficiency of absorbed photon energy to acoustic energy is approximately 40% and is limited by finite collision-induced relaxation rates between the two lowest-lying excited electronic states of O(2). PAS also shows great potential for high-resolution line shape measurements: calculated and experimental values for the PAS system response differ by about 1%. PMID- 20590263 TI - Reflectance changes during shock-induced phase transformations in metals. AB - In performing shock wave experiments to study the characteristics of metals at high pressures, wave profiles (i.e., velocity measurements of the surface of the sample) are an established and useful way to study phase transformations. For example, a sudden change in the velocity or its slope can occur when the phase transformation induces a large volume change leading to a change in particle velocity. Allowing the shock to release into a transparent window that is in contact with the sample surface allows the study of conditions away from the shock Hugoniot. However, in cases where the wave profile is not definitive, an additional phase-transformation diagnostic is often useful. Changes in the electronic structure of the atoms in the crystal offer opportunities to develop new phase-change diagnostics. We have studied optical reflectance changes for several shock-induced phase transformations to see whether reflectance changes might be a generally applicable phase-transformation diagnostic. Shocks were produced by direct contact with explosives or with impacts from guns. Optical wavelengths for the reflectance measurements ranged from 355 to 700 nm. We studied samples of tin, iron, gallium, and cerium as each passed through a phase transformation during shock loading and, if observable, a reversion upon unloading. In addition to metals with complicated phase diagrams, we also measured dynamic, pressure-induced changes in the reflectivity of aluminum. For rapid solid-solid phase changes in tin and iron, we saw small changes in the surface scattering characteristics, perhaps from voids or rough areas frozen into the surface of the sample as it transformed to a new crystal structure. For melt in gallium and cerium, we saw changes in the wavelength dependence of the reflectance, and we surmise that these changes may result from changes in the crystal electronic structure. It appears that reflectance measurements can be a significant part of a larger suite of diagnostics to search for difficult-to detect phase transformations. PMID- 20590264 TI - Self-focused acoustic ejectors for viscous liquids. AB - Self-focused acoustic ejectors using the Fresnel zone plate (FZP) have been developed for ejecting viscous liquids, without nozzle, in the drop-on-demand mode. The FZP is composed of a lead zirconate titanate piezoelectric plate patterned with a series of annular electrodes, with the unelectroded region of the plate removed. Our results show that the acoustic waves are effectively self focused by constructive interference in glycerin (with a viscosity of 1400 mPa s), giving small focal points with a high pressure. Due to the high attenuation, the wave pressure decreases significantly with the distance from the FZP. Nevertheless, the pressure at the focal points 2.5 and 6.5 mm from the FZP is high enough to eject glycerin droplets in the drop-on-demand mode. Driven by a simple wave train comprising a series of sinusoidal voltages with an amplitude of 35 V, a frequency of 4.28 MHz, and a duration of 2 ms, the ejector can eject fine glycerin droplets with a diameter of 0.4 mm at a repetition frequency of 120 Hz in a downward direction. Droplets of other viscous liquids, such as the prepolymer of an epoxy with a viscosity of 2000 mPa s, can also be ejected in the drop-on-demand mode under similar conditions. PMID- 20590265 TI - Stray magnetic field compensation with a scalar atomic magnetometer. AB - We describe a system for the compensation of time-dependent stray magnetic fields using a dual channel scalar magnetometer based on nonlinear Faraday rotation in synchronously optically pumped Cs vapor. We detail the active control strategy, with an emphasis on the electronic circuitry, based on a simple phase-locked-loop integrated circuit. The performance and limits of the system developed are tested and discussed. The system was applied to significantly improve the detection of free induction decay signals from protons of remotely magnetized water precessing in an ultralow magnetic field. PMID- 20590266 TI - The influence of refractive index change and initial bending of cantilevers on the optical lever readout method. AB - It has been speculated that the initial bending of cantilevers has a major influence on the detector signal in a cantilever-based sensor using the optical lever readout method. We have investigated theoretically as well as experimentally the changes induced in the detector signal when the optical lever technique is used to monitor a cantilever with initial bending during changes in the refractive index of the surrounding media. We find that for changes in refractive index as small as 10(-4) the detector signal is highly dependent on the initial bending of the cantilever. The findings are validated experimentally using an environmental chamber and varying the pressure. We sketch routes to circumvent the problem and formulas suitable for data treatment are given. PMID- 20590267 TI - A simple method for measuring the superhydrophobic contact angle with high accuracy. AB - A modified selected-plane method for contact angle (theta) measurement is proposed in this study that avoids the difficulty of finding the real contact point and image-distortion effects adjacent to the contact point. This method is particularly suitable for superhydrophobic surfaces. The sessile-drop method coupled with the tangent line is the most popular method to find the contact angle in literature, but it entails unavoidable errors in determining the air solid base line due to the smoothness problem and substrate tilting. In addition, the tangent-line technique requires finding the actual contact point. The measurement error due to the base line problem becomes more profound for superhydrophobic surfaces. A larger theta deviation results from a more superhydrophobic surface with a fixed base line error. The proposed modified selected-plane method requires only four data points (droplet apex, droplet height, and two interfacial loci close to the air-solid interface), avoiding the problem of the sessile-drop-tangent method in finding the contact point and saving the trouble of the sessile-drop-fitting method for best fitting of the numerous edge points with the theoretical profile. A careful error analysis was performed, and a user-friendly program was provided in this work. This method resulted in an accurate theta measurement and a method that was much improved over the classical selected plane and the sessile-drop-tangent methods. The theta difference between this method and the sessile-drop-fitting method was found to be less than three degrees. PMID- 20590268 TI - High-shear-rate capillary viscometer for inkjet inks. AB - A capillary viscometer developed to measure the apparent shear viscosity of inkjet inks at high apparent shear rates encountered during inkjet printing is described. By using the Weissenberg-Rabinowitsch equation, true shear viscosity versus true shear rate is obtained. The device is comprised of a constant-flow generator, a static pressure monitoring device, a high precision submillimeter capillary die, and a high stiffness flow path. The system, which is calibrated using standard Newtonian low-viscosity silicone oil, can be easily operated and maintained. Results for measurement of the shear-rate-dependent viscosity of carbon-black pigmented water-based inkjet inks at shear rates up to 2 x 10(5) s( 1) are discussed. The Cross model was found to closely fit the experimental data. Inkjet ink samples with similar low-shear-rate viscosities exhibited significantly different shear viscosities at high shear rates depending on particle loading. PMID- 20590269 TI - Biphase sinusoidal oscillator based on negative resistor. AB - This paper describes a biphase sinusoidal generator which provides two signals: v(ref)=V(M) sin(omegat) and v(out)=V(M) sin(omegat+DeltaPhi), where DeltaPhi is in the range 0, pi/2 or -pi/2, 0 and is not dependent on the frequency value. It is based on a negative resistor and it requires very few components. SPICE simulations and measurements on an experimental setup confirm the theoretical analysis. PMID- 20590270 TI - Identification of superconducting phases in ceramic particles by magnetic field induced forces using a magnetized wire. AB - A new equipment for minority phase analysis of superconducting (SC) phases within chemically inhomogeneous ceramic grains using a high gradient magnetic field or field induced effect of torque is presented. Single grains down to 20 microm are either captured by a magnetized iron wire or identified because of their torque movement in a pulsed magnetic field. An assembly of many hundreds of grains can be investigated for minor quantities of SC phases from 80 K up to room temperature. A maximum field of up to 100-140 mT allows us to reliably identify SC grains and evaluate their SC critical temperatures T(c). Localization of SC grains allows us to extract them for further analysis. Experiments with YBa(2)Cu(3)O(2-delta) grains demonstrated that T(c) values evaluated in such a way are rather close to those, which are determined by magnetization measurements. PMID- 20590271 TI - High performance conductivity monitoring instrument with pulsating sensor. AB - We present an unconventional but high performance pulsating conductivity monitoring instrument constructed by using a new class of sensor, viz., pulsating sensor developed in house. The design consists of a special type of logic gate oscillator (LGO) powered by 5 V direct current (dc). The conductivity cell constitutes a part of LGO. In this conductivity meter the primary signal generated from the sensor is directly in digital domain which is easily transmitted either to a personal computer or to a stand-alone embedded system. Hence it reduces the hardware components making the instrumentation highly simplified. The output of the instrument is pulse frequency which is directly related to the conductivity of solution used for measurement. The relation between pulse frequency and conductivity is determined following a multipoint calibration technique developed in our laboratory using a series of KCl standards. The performance of the instrument is demonstrated with a few examples which reveal the diverse application of this new approach of measurement technique. PMID- 20590272 TI - Note: New feedthrough insulation method for the dielectric spectroscopy under ultrahigh pressure conditions. AB - We present a new technique to prepare insulated channels for the high pressure cell used in broadband dielectric spectroscopy. The cell resists corrosion or other chemical reactions from the reactive sample liquids. The cell maintains electrical insulation between electrode contacts better than 100 GOmega as well as good mechanical properties in broad temperature range of -80 to +100 degrees C and under extremely high pressures up to 1.8 GPa. PMID- 20590273 TI - Note: Exciting higher-order flexural modes of freestanding microstructures with square wave driving signals. AB - We examine using the harmonics of low fundamental frequency (f(1)) square waveforms to electrostatically excite higher-order flexural modes of a micromechanical structure in higher (>f(1)) frequency regimes. Square wave signals swept between a fundamental frequency range of approximately 0-333 kHz demonstrated an effective high magnitude spectral excitation of approximately 0-1 MHz. This enabled optical heterodyne detection of structural resonant frequencies above 333 kHz. Low frequency square wave signals were also used to selectively excite modes at higher frequencies. PMID- 20590274 TI - Note: A simple dual polarity dual nanoelectrospray ionization source for ion/ion reactions. AB - A continuously operated dual polarity dual nanoelectrospray ionization source has been constructed and tested. A commercial quadrupole ion trap mass spectrometer was modified to accumulate and trap ions of opposite charge. All changes to the commercial three-dimensional quadrupole ion trap have been made external to the instrument outside of the vacuum system. Few hardware modifications were required because the two emitters send ion beams through the same transmission guides. Computer controlled source voltage polarities are switched quickly and efficiently to transmit one of two continuously generated ion beams. With customized software, this design has proved simple to implement and to operate. PMID- 20590275 TI - Note: Three-omega method to measure thermal properties of subnanoliter liquid samples. AB - There are growing needs to measure the thermal properties of small-volume liquid samples in various fields of bioengineering and microfluidics. Accordingly, there have been efforts toward miniaturization of the sensing device without substantially sacrificing the sensitivity. The minimum sample volume required for quantitative thermal analysis is currently in the 10 nl scale. In this work, we describe microfabricated sensors and a modified three-omega data-analysis scheme to determine the thermal conductivity k and volumetric heat capacity rhoc(p) of samples of a few hundred picoliters. In experiments using several reference liquids, the technique measured k and rhoc(p) of 750 and 375 pl samples. The measurement accuracies were approximately 10% for k and approximately 15% for rhoc(p). PMID- 20590276 TI - Note: A low leakage liquid seal for micromachined gas valves. AB - We report a method for addressing gas leakage in micromachined valves. The valves used for evaluating the proposed concept utilize a silicon valve seat that is bonded to a glass substrate and actuated by a piezoelectric stack, all of which are assembled within a ceramic package. The sealing method uses the capillary forces of a liquid sealant on the valve seat to reduce gas leakage below measurable limits. The gas leak rates are compared in valves with and without the seal enhancement. For example, a valve closes against 13.5 kPa with 10 V actuation, compared to 40 V required without the enhancement. Leakage is also evaluated for liquid flow. PMID- 20590277 TI - Note: Rigid holder to host and bend a crystal for multiple volume reflection of a particle beam. AB - A holder to lodge and bend a silicon crystal to excite multivolume reflection of a high-energy particle beam has been designed and fabricated. A mechanically robust and stable structure fastens a crystal at best condition for experiments. The holder has allowed the observation of 12-time repeated volume reflection with very high efficiency. We detail the most important features behind the construction of the holder together with the characterization of the crystal being bent by the holder. PMID- 20590279 TI - The effect of target strain error on plantar tissue stress. AB - Accurate quantification of soft tissue properties, specifically the stress relaxation behavior of viscoelastic tissues such as plantar tissue, requires precise testing under physiologically relevant loading. However, limitations of testing equipment often result in target strain errors that can contribute to large stress errors and confound comparative results to an unknown extent. Previous investigations have modeled this artifact, but they have been unable to obtain empirical data to validate their models. Moreover, there are no studies that address this issue for plantar tissue. The purpose of this research was to directly measure the difference in peak force for a series of small target strain errors within the range of our typical stress relaxation experiments for the subcutaneous plantar soft tissue. Five plantar tissue specimens were tested to seven incremental target strain error levels of -0.9%, -0.6%, -0.3%, 0.0%, 0.3%, 0.6%, and 0.9%, so as to undershoot and overshoot the target displacement in 0.3% increments. The imposed strain errors were accurately attained using a special compensation feature of our materials testing software that can drive the actuator to within 0% (1-2 microm) of the target level for cyclic tests. Since stress relaxation tests are not cyclic, we emulated the ramp portion of our stress relaxation tests with 5 Hz triangle waves. The average total stress variation for all specimens was 25+/-5%, with the highest and lowest stresses corresponding to the largest and smallest strain errors of 0.9% and -0.9%, respectively. A strain overshoot of 0.3%, the target strain error observed in our typical stress relaxation experiments, corresponded to an average stress overshoot of 3+/-1%. Plantar tissue in compression is sensitive to small target strain errors that can result in stress errors that are several fold larger. The extent to which the overshoot may affect the peak stress will likely differ in magnitude for other soft tissues and loading modes. PMID- 20590280 TI - A mechanism to explain physiological lubrication. AB - A new mechanism of physiological lubrication is proposed to explain how low viscosity synovial fluid prevents articular surfaces from contacting and wearing. The new mechanism is based on the hypothesis that the hyaluronic acid chains in synovial fluid bind to the cartilage surfaces through electrostatic charges, with the phospholipid layer on an articular surface supplying the necessary attractive charges. The stationary hyaluronic acid network causes a large hydrodynamic resistance to outward flow from the gap. To determine the effectiveness of the network in preventing contact, squeeze-film flow between two incompressible, permeable disks is analyzed when a constant load is suddenly applied, and the solvent--synovial fluid minus the hyaluronic acid--escapes through the network and through the permeable disks. The analysis yields the approximate time for the gap distance to decrease to asperity size. For realistic physiological parameters, the time for the surfaces to contact is a minimum of several minutes and likely much longer. The role of albumin in the synovial fluid is included because the large protein molecules are trapped by the small openings in the hyaluronic acid network, which increases the flow resistance of the network and thereby delays contact of the surfaces. PMID- 20590281 TI - An EMG-driven biomechanical model that accounts for the decrease in moment generation capacity during a dynamic fatigued condition. AB - Although it is well known that fatigue can greatly reduce muscle forces, it is not generally included in biomechanical models. The aim of the present study was to develop an electromyographic-driven (EMG-driven) biomechanical model to estimate the contributions of flexor and extensor muscle groups to the net joint moment during a nonisokinetic functional movement (squat exercise) performed in nonfatigued and in fatigued conditions. A methodology that aims at balancing the decreased muscle moment production capacity following fatigue was developed. During an isometric fatigue session, a linear regression was created linking the decrease in force production capacity of the muscle (normalized force/EMG ratio) to the EMG mean frequency. Using the decrease in mean frequency estimated through wavelet transforms between dynamic squats performed before and after the fatigue session as input to the previous linear regression, a coefficient accounting for the presence of fatigue in the quadriceps group was computed. This coefficient was used to constrain the moment production capacity of the fatigued muscle group within an EMG-driven optimization model dedicated to estimate the contributions of the knee flexor and extensor muscle groups to the net joint moment. During squats, our results showed significant increases in the EMG amplitudes with fatigue (+23.27% in average) while the outputs of the EMG-driven model were similar. The modifications of the EMG amplitudes following fatigue were successfully taken into account while estimating the contributions of the flexor and extensor muscle groups to the net joint moment. These results demonstrated that the new procedure was able to estimate the decrease in moment production capacity of the fatigued muscle group. PMID- 20590282 TI - Particle-image velocimetry study of a pediatric ventricular assist device. AB - Particle-image velocimetry (PIV) was used to visualize the flow within an optically transparent pediatric ventricular assist device (PVAD) under development in our laboratory. The device studied is a diaphragm type pulsatile pump with an ejection volume of 30 ml per beating cycle intended for temporary cardiac assistance as a bridge to transplantation or recovery in children. Of particular interest was the identification of flow patterns, including regions of stagnation and/or strong turbulence that often promote thrombus formation and hemolysis, which can degrade the usefulness of such devices. For this purpose, phase-locked PIV measurements were performed in planes parallel to the diaphragm that drives the flow in the device. The test fluid was seeded with 10 microm polystyrene spheres, and the motion of these particles was used to determine the instantaneous flow velocity distribution in the illumination plane. These measurements revealed that flow velocities up to 1.0 m/s can occur within the PVAD. Phase-averaged velocity fields revealed the fixed vortices that drive the bulk flow within the device, though significant cycle-to-cycle variability was also quite apparent in the instantaneous velocity distributions, most notably during the filling phase. This cycle-to-cycle variability can generate strong turbulence that may contribute to greater hemolysis. Stagnation regions have also been observed between the input and output branches of the prototype, which can increase the likelihood of thrombus formation. PMID- 20590283 TI - Trans-thrombus blood pressure effects in abdominal aortic aneurysms. AB - How much and how the thrombus supports the wall of an abdominal aortic aneurysm (AAA) is unclear. While some previous studies have indicated that thrombus lacks the mechanical integrity to support much load compared with the aneurysm wall, others have shown that removing thrombus in computational AAA models drastically changes aneurysm wall stress. Histopathological studies have shown that thrombus properties vary through the thickness and it can be porous. The goal of this study is to explore the variations in thrombus properties, including the ability to isolate pressure from the aneurysm wall, incomplete attachment, and their effects on aneurysm wall stress, an important parameter in determining risk for rupture. An analytical model comprised of cylinders and two patient specific models were constructed with pressurization boundary conditions applied at the lumen or the thrombus/aneurysm wall interface (to simulate complete transmission of pressure through porous thrombus). Aneurysm wall stress was also calculated in the absence of thrombus. The potential importance of partial thrombus attachment was also analyzed. Pressurizing at either surface (lumen versus interface) made little difference to mean von Mises aneurysm wall stress values with thrombus completely attached (3.1% analytic, 1.2% patient specific) while thrombus presence reduced mean von Mises stress considerably (79% analytic, 40-46% patient specific) in comparison to models without it. Peak von Mises stresses were similarly influenced with pressurization surface differing slightly (3.1% analytic, 1.4% patient specific) and reductions in stress by thrombus presence (80% analytic, 28-37% patient specific). The case of partial thrombus attachment was investigated using a cylindrical model in which there was no attachment between the thrombus and aneurysm wall in a small area (10 deg). Applying pressure at the lumen resulted in a similar stress field to fully attached thrombus, whereas applying pressure at the interface resulted in a 42% increase in peak aneurysm wall stress. Taken together, these results show that the thrombus can have a wall stress reducing role even if it does not shield the aneurysm wall from direct pressurization--as long as the thrombus is fully attached to the aneurysm wall. Furthermore, the potential for porous thrombus to transmit pressure to the interface can result in a considerable increase in aneurysm wall stress in cases of partial attachment. In the search for models capable of accurately assessing the risk for rupture, the nature of the thrombus and its attachment to the aneurysm wall must be carefully assessed. PMID- 20590284 TI - Carotid bifurcation hemodynamics in older adults: effect of measured versus assumed flow waveform. AB - Recent work has illuminated differences in carotid artery blood flow rate dynamics of older versus young adults. To what degree flow waveform shape, and indeed the use of measured versus assumed flow rates, affects the simulated hemodynamics of older adult carotid bifurcations has not been elucidated. Image based computational fluid dynamics models of N=9 normal, older adult carotid bifurcations were reconstructed from magnetic resonance angiography. Subject specific hemodynamics were computed by imposing each individual's inlet and outlet flow rates measured by cine phase-contrast magnetic resonance imaging or by imposing characteristic young and older adult flow waveform shapes adjusted to cycle-averaged flow rates measured or allometrically scaled to the inlet and outlet areas. Despite appreciable differences in the measured versus assumed flow conditions, the locations and extents of low wall shear stress and elevated relative residence time were broadly consistent; however, the extent of elevated oscillatory shear index was substantially underestimated, more by the use of assumed cycle-averaged flow rates than the assumed flow waveform shape. For studies of individual vessels, use of a characteristic flow waveform shape is likely sufficient, with some benefit offered by scaling to measured cycle averaged flow rates. For larger-scale studies of many vessels, ranking of cases according to presumed hemodynamic or geometric risk is robust to the assumed flow conditions. PMID- 20590285 TI - Gait modification via verbal instruction and an active feedback system to reduce peak knee adduction moment. AB - The purpose of this study was to introduce a simple gait training method using real-time gait modification to reduce the peak knee adduction moment during walking by producing a subtle weight bearing shift to the medial side of the foot. The hypothesis of this study was that this weight shift could be achieved via either verbal instruction or an active feedback system, and that the weight shift would result in a reduction in the first peak knee adduction moment compared with the control tests. Nine individuals were tested during walking using two intervention methods: verbal instruction and an active feedback system placed on the right shoe. The first peak of the knee adduction moment for each condition was assessed using a motion capture system and force plate. The active feedback system significantly reduced (14.2%) the peak knee adduction moment relative to the control. This study demonstrated that a subtle weight bearing shift to the medial side of the foot produced with an active feedback system during walking reduced the first peak of the knee adduction moment and suggests the potential application of this method to slow the rate of progression of medial compartment knee osteoarthritis. PMID- 20590287 TI - Determination of passive moment-angle relationships at the trapeziometacarpal joint. AB - While modeling the trapeziometacarpal (TMC) joint for determination of tendon forces, the TMC has been considered frictionless and passive moments created by soft tissues neglected. This, however, becomes inaccurate when reaching the joint end range of motion and considering that the TMC is entirely crossed by a complex network of skin, ligaments, soft tissues, and tendons. The objective of this study was to evaluate the passive moments with respect to joint posture in order to further include this relationship in biomechanical modeling. An experimental method was proposed to estimate in vivo a global passive moment including the sum of the actions of each passive anatomical structure. An external force was applied at the level of the metacarpophalangeal joint in various directions ranging from neutral position to full extension and full adduction to full abduction. The passive moment was computed and expressed as a function of the adopted joint angles. An exponential regression was then developed to fit the experimental data and to propose a generic passive moment model. Results showed a good agreement between the proposed exponential regression model and the experimental measures. Moreover, it was shown that joint stiffness could represent more than 60% of the net joint moment during a typical pulp grip task. These results showed the necessity to include the data in biomechanical modeling. The results may help predict more realistic tendons force especially in abduction/adduction muscles. PMID- 20590286 TI - Validation of the cat as a model for the human lumbar spine during simulated high velocity, low-amplitude spinal manipulation. AB - High-velocity, low-amplitude spinal manipulation (HVLA-SM) is an efficacious treatment for low back pain, although the physiological mechanisms underlying its effects remain elusive. The lumbar facet joint capsule (FJC) is innervated with mechanically sensitive neurons and it has been theorized that the neurophysiological benefits of HVLA-SM are partially induced by stimulation of FJC neurons. Biomechanical aspects of this theory have been investigated in humans while neurophysiological aspects have been investigated using cat models. The purpose of this study was to determine the relationship between human and cat lumbar spines during HVLA-SM. Cat lumbar spine specimens were mechanically tested, using a displacement-controlled apparatus, during simulated HVLA-SM applied at L5, L6, and L7 that produced preload forces of approximately 25% bodyweight for 0.5 s and peak forces that rose to 50-100% bodyweight within approximately 125 ms, similar to that delivered clinically. Joint kinematics and FJC strain were measured optically. Human FJC strain and kinematics data were taken from a prior study. Regression models were established for FJC strain magnitudes as functions of factors species, manipulation site, and interactions thereof. During simulated HVLA-SM, joint kinematics in cat spines were greater in magnitude compared with humans. Similar to human spines, site-specific HVLA-SM produced regional cat FJC strains at distant motion segments. Joint motions and FJC strain magnitudes for cat spines were larger than those for human spine specimens. Regression relationships demonstrated that species, HVLA-SM site, and interactions thereof were significantly and moderately well correlated for HVLA SM that generated tensile strain in the FJC. The relationships established in the current study can be used in future neurophysiological studies conducted in cats to extrapolate how human FJC afferents might respond to HVLA-SM. The data from the current study warrant further investigation into the clinical relevance of site targeted HVLA-SM. PMID- 20590288 TI - Reverse pupillary block slows iris contour recovery from corneoscleral indentation. AB - Corneoscleral indentation changes the iris contour and alters the angle between the iris and cornea. Although this effect has long been observed, the mechanism by which it occurs remains poorly understood. Previous theoretical research has shown that corneoscleral indentation can deform the eye globe and consequently rotate the iris root. In this work, we studied the fluid-structure interaction between the iris and aqueous humor, driven by iris root rotation. The iris root rotation obtained from our previous whole-globe model was used as a boundary condition for a fluid-structure interaction finite element model of the anterior eye. We studied the effect of two parameters-rotation angle and indentation speed on the iris contour and aqueous humor dynamics. We found that posterior rotation of the iris root caused posterior bowing of the iris. After the iris root was returned to its original orientation, the aqueous humor was trapped in the anterior chamber because the iris tip pinned against the lens (reverse pupillary block). After 0.5-2 min of simulation, aqueous humor secretion into the posterior chamber and outflow from the anterior chamber allowed the system to return to its original steady state flow condition. The faster or farther the iris root rotated, the longer it took to return to steady state. Reverse pupillary block following corneoscleral indentation is a possible explanation for the clinical observation that prevention of blinking causes the iris to drift forward. PMID- 20590289 TI - Reduction of procoagulant potential of b-datum leakage jet flow in bileaflet mechanical heart valves via application of vortex generator arrays. AB - Current designs of bileaflet mechanical heart valves put patients at an increased risk of thromboembolism. In particular, regurgitant flow through the b-datum line is associated with nonphysiologic flow characteristics such as elevated shear stresses, regions of recirculation, and increased mixing, all of which may promote thrombus formation. We have previously shown that passive flow control in the form of vortex generators mounted on the downstream leaflet surfaces can effectively diminish turbulent stresses. The objective of the current work is thus to determine the effect of vortex generators on the thromboembolic potential of the b-datum line leakage jet and to correlate that effect with the vortex generator-induced changes to the flow structure. Flow experiments were performed using a steady model of the transient b-datum line jet. These experiments encompassed flow visualization to gain an overall picture of the flow system, particle image velocimetry to quantify the flow field in detail, and in vitro experiments with human blood to quantify thrombus formation in response to the applied passive flow control. Thrombus formation was quantified over time by an assay for thrombin-antithrombin III (TAT III). In comparing results with and without vortex generators, significantly lower mean TAT III levels were observed at one time point for the case with vortex generators. Also, the TAT III growth rate of the case with vortex generators was significantly lower. While no differences in jet spreading were found with and without vortex generators, lower peak turbulent stresses were observed for the case with vortex generators. The results thus demonstrate the potential of applying passive flow control to cardiovascular hardware in order to mitigate the hemodynamic factors leading to thrombus formation. PMID- 20590290 TI - Mechanical analysis of the preferred strategy selection in human stumble recovery. AB - We use simple walking models, based on mechanical principles, to study the preferred strategy selection in human stumble recovery. Humans typically apply an elevating strategy in response to a stumble in early swing and midswing, for which the perturbed step is lengthened in a continuation of the original step. A lowering strategy is executed for stumbles occurring at midswing or late swing, for which the perturbed swing foot is immediately placed on the ground and the recovery is executed in the subsequent step. There is no clear understanding of why either strategy is preferred over the other. We hypothesize that the human strategy preference is the result of an attempt to minimize the cost of successful recovery. We evaluate five hypothesized measures for recovery cost, focusing on the energetic cost of active recovery limb placement. We determine all hypothesized cost measures as a function of the chosen recovery strategy and the timing of the stumble during gait. Minimization of the cost measures based on the required torque, impulse, power and torque/time results in a humanlike strategy preference. The cost measure based on swing work does not predict a favorable strategy as a function of the gait phase. PMID- 20590292 TI - Evaluation of negative fixed-charge density in tissue-engineered cartilage by quantitative MRI and relationship with biomechanical properties. AB - Applying tissue-engineered cartilage in a clinical setting requires noninvasive evaluation to detect the maturity of the cartilage. Magnetic resonance imaging (MRI) of articular cartilage has been widely accepted and applied clinically in recent years. In this study, we evaluated the negative fixed-charge density (nFCD) of tissue-engineered cartilage using gadolinium-enhanced MRI and determined the relationship between nFCD and biomechanical properties. To reconstruct cartilage tissue, articular chondrocytes from bovine humeral heads were embedded in agarose gel and cultured in vitro for up to 4 weeks. The nFCD of the cartilage was determined using the MRI gadolinium exclusion method. The equilibrium modulus was determined using a compressive stress relaxation test, and the dynamic modulus was determined by a dynamic compression test. The equilibrium compressive modulus and dynamic modulus of the tissue-engineered cartilage increased with an increase in culture time. The nFCD value--as determined with the [Gd-DTPA(2-)] measurement using the MRI technique--increased with culture time. In the regression analysis, nFCD showed significant correlations with equilibrium compressive modulus and dynamic modulus. From these results, gadolinium-enhanced MRI measurements can serve as a useful predictor of the biomechanical properties of tissue-engineered cartilage. PMID- 20590291 TI - Axons pull on the brain, but tension does not drive cortical folding. AB - During human brain development, the cerebral cortex undergoes substantial folding, leading to its characteristic highly convoluted form. Folding is necessary to accommodate the expansion of the cerebral cortex; abnormal cortical folding is linked to various neurological disorders, including schizophrenia, epilepsy, autism, and mental retardation. Although this process requires mechanical forces, the specific force-generating mechanisms that drive folding remain unclear. The two most widely accepted hypotheses are as follows: (1) Folding is caused by differential growth of the cortex and (2) folding is caused by mechanical tension generated in axons. Direct evidence supporting either theory, however, is lacking. Here we show that axons are indeed under considerable tension in the developing ferret brain, but the patterns of tissue stress are not consistent with a causal role for axonal tension. In particular, microdissection assays reveal that significant tension exists along axons aligned circumferentially in subcortical white matter tracts, as well as those aligned radially inside developing gyri (outward folds). Contrary to previous speculation, however, axonal tension is not directed across developing gyri, suggesting that axon tension does not drive folding. On the other hand, using computational (finite element) models, we show that differential cortical growth accompanied by remodeling of the subplate leads to outward folds and stress fields that are consistent with our microdissection experiments, supporting a mechanism involving differential growth. Local perturbations, such as temporal differences in the initiation of cortical growth, can ensure consistent folding patterns. This study shows that a combination of experimental and computational mechanics can be used to evaluate competing hypotheses of morphogenesis, and illuminate the biomechanics of cortical folding. PMID- 20590293 TI - The response of human aortic endothelial cells in a stenotic hemodynamic environment: effect of duration, magnitude, and spatial gradients in wall shear stress. AB - Inflammation plays a key role in the development and stability of coronary plaques. Endothelial cells alter their expression in response to wall shear stress (WSS). Straight/tubular and asymmetric stenosis models were designed to study the localized expression of atheroprone molecules and inflammatory markers due to the presence of the spatial wall shear stress gradients created by an eccentric plaque. The effects of steady wall shear stress duration (0-24 h) and magnitude (4.5-18 dynes/cm(2)) were analyzed in human abdominal aortic endothelial cells through quantitative real-time polymerase chain reaction (PCR) and immunofluorescence analysis in straight/tubular models. Regional expression was assessed by immunofluorescence and confocal microscopy in stenosis models. Under steady fully developed flow, endothelial cells exhibited a sustained increase in levels of atheroprotective genes with WSS duration and magnitude. The local response in the stenosis model showed that expression of endothelial nitric oxide synthase and Kruppel-like factor 2 is magnitude rather than gradient dependent. A WSS magnitude dependent transient increase in translocation of transcription factor nuclear factor kappaB was observed. Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin exhibited a sustained increase in protein expression with time. The mRNA levels of these molecules were transiently upregulated and this was followed by a decrease in expression to levels lower than static controls. Regionally, increased inflammatory marker expression was observed in regions of WSS gradients both proximal and distal to the stenosis when compared with the uniform flow regions, whereas the atheroprotective markers were expressed to a greater extent in regions of elevated WSS magnitudes. The results from the straight/tubular model cannot explain the regional variation seen in the stenosis models. This may help explain the localization of inflammatory cells at the shoulders of plaques in vivo. PMID- 20590294 TI - Marker-based reconstruction of the kinematics of a chain of segments: a new method that incorporates joint kinematic constraints. AB - The aim of skin-marker-based motion analysis is to reconstruct the motion of a kinematical model from noisy measured motion of skin markers. Existing kinematic models for reconstruction of chains of segments can be divided into two categories: analytical methods that do not take joint constraints into account and numerical global optimization methods that do take joint constraints into account but require numerical optimization of a large number of degrees of freedom, especially when the number of segments increases. In this study, a new and largely analytical method for a chain of rigid bodies is presented, interconnected in spherical joints (chain-method). In this method, the number of generalized coordinates to be determined through numerical optimization is three, irrespective of the number of segments. This new method is compared with the analytical method of Veldpaus et al. [1988, "A Least-Squares Algorithm for the Equiform Transformation From Spatial Marker Co-Ordinates," J. Biomech., 21, pp. 45-54] (Veldpaus-method, a method of the first category) and the numerical global optimization method of Lu and O'Connor [1999, "Bone Position Estimation From Skin Marker Co-Ordinates Using Global Optimization With Joint Constraints," J. Biomech., 32, pp. 129-134] (Lu-method, a method of the second category) regarding the effects of continuous noise simulating skin movement artifacts and regarding systematic errors in joint constraints. The study is based on simulated data to allow a comparison of the results of the different algorithms with true (noise- and error-free) marker locations. Results indicate a clear trend that accuracy for the chain-method is higher than the Veldpaus-method and similar to the Lu method. Because large parts of the equations in the chain-method can be solved analytically, the speed of convergence in this method is substantially higher than in the Lu-method. With only three segments, the average number of required iterations with the chain-method is 3.0+/-0.2 times lower than with the Lu-method when skin movement artifacts are simulated by applying a continuous noise model. When simulating systematic errors in joint constraints, the number of iterations for the chain-method was almost a factor 5 lower than the number of iterations for the Lu-method. However, the Lu-method performs slightly better than the chain method. The RMSD value between the reconstructed and actual marker positions is approximately 57% of the systematic error on the joint center positions for the Lu-method compared with 59% for the chain-method. PMID- 20590295 TI - A large strain material model for soft tissues with functionally graded properties. AB - The reaction of articular cartilage and other soft tissues to mechanical loads has been characterized by coupled hydraulic (H) and mechanical (M) processes. An enhanced biphasic material model is presented, which may be used to describe the load response of soft tissue. A large-strain numerical approach of HM coupled processes has been applied. Physical and geometrical nonlinearities, as well as anisotropy and intrinsic rate-dependency of the solid skeleton have been realized using a thermodynamically consistent approach. The presented material model has been implemented into the commercially available finite element code MSC MARC. Initial verification of the model has been conducted analytically in tendonlike structures. The poroelastic and intrinsic viscoelastic features of the model were compared with the experimental data of an unconfined compression test of agarose hydrogel. A recent example from the area of cartilage research has been modeled, and the mechanical response was compared with cell viability. All examples showed good agreement between numerical and analytical/experimental results. PMID- 20590296 TI - Biomechanical and elastographic analysis of mesenchymal stromal cell treated tissue following surgery. AB - Hernia repair continues to be a problem facing surgeons today, particularly because of the high incidence of reoccurrence. This work presents preliminary data of a pioneering effort to investigate the effect of mesenchymal stromal cells (MSCs) on mechanical property enhancement in full thickness fascial defects. Heparinized MSCs harvested from a rabbit's tibia/iliac crest were applied to two fascial defects on the rabbit's abdominal wall, with two other defects acting as controls (no MSCs added). After an 8 week recovery period, the entire abdominal fascia was harvested for mechanical property testing and elastographic strain analysis. Preliminary results from uniaxial tensile testing indicate a significant increase in the modulus of toughness strain energy, with at least a 50% increase in the MSC treated defects as compared with the control defects. Results from the elastographic strain analysis show excellent correlation in the calibration of the elastography to the uniaxial tensile test, with nearly identical moduli of elasticity. In addition, the elastographs clearly show tissue property heterogeneity at all stages of tensile testing. The MSC treated tissue demonstrates promise of enhanced material properties over that of the nontreated tissue; testing and analysis is ongoing. The elastography provides pixel-level description of tissue property variations providing critical information on wound healing effectiveness that would be impossible with other methods. In the ongoing research, optical elastography, in combination with the traditional tensile test and tissue histology, will be used to characterize localized biomechanical properties directly within the defect area and to locate "crack" initiation and propagation sights as the material is strained to rupture. PMID- 20590297 TI - Deformable self-propelled particles with a global coupling. AB - We have proposed a model of deformable self-propelled particles in which the time evolution equations are given in terms of the center-of-mass velocity and a nematic order parameter representing the motion-induced deformation [T. Ohta and T. Ohkuma, Phys. Rev. Lett. 102, 154101 (2009)]. We investigate its many-body problem applying a global orientational coupling. Depending on the strength of the interaction, the self-propelled particles exhibit various kinds of collective dynamics and chaotic behavior: a ballistic procession state, a scattered state, a coherently phase synchronized state, two types of in-phase synchronized state, and an anomalously diffusive state. The phase reduction method for the weak coupling regime reveals the bifurcations between the secular collective motions. The phase boundary among the chaos regime and the synchronized regimes is determined by the linear stability analysis of the synchronized states. PMID- 20590298 TI - Chaotic mixing via streamline jumping in quasi-two-dimensional tumbled granular flows. AB - We study, numerically and analytically, the singular limit of a vanishing flowing layer in tumbled granular flows in quasi-two-dimensional rotating containers. The limiting behavior is found to be identical under the two versions of the kinematic continuum model of such flows, and the transition to the limiting dynamics is analyzed in detail. In particular, we formulate the no-shear-layer dynamical system as a piecewise isometry. It is shown how such a discontinuous map, through the concordant mechanism of streamline jumping, leads to the physical mixing of granular matter. The dependence of the dynamics of Lagrangian particle trajectories on the tumbler fill fraction is also established through Poincare sections, and, in the special case of a half-full tumbler, chaotic behavior is shown to disappear completely in the singular limit. At other fill levels, stretching in the sense of shear strain is replaced by spreading due to streamline jumping. Finally, we use finite-time Lyapunov exponents to establish the manifold structure and understand "how chaotic" the limiting piecewise isometry is. PMID- 20590299 TI - Some two-dimensional parameter spaces of a Chua system with cubic nonlinearity. AB - In this paper we investigate three two-dimensional parameter spaces of a three parameter set of autonomous differential equations used to model the Chua oscillator, where the piecewise-linear function usually taken to describe the nonlinearity of the Chua diode has been replaced by a cubic polynomial. It is made by using three independent two-dimensional cross sections of the three dimensional parameter space generated by the model, which contains three parameters. We show that, independent of the parameter set considered in plots, all the diagrams present periodic structures embedded in a large chaotic region, and we also show that these structures organize themselves in period-adding cascades. We argue that these selected two-dimensional cross sections can be representative of the three-dimensional parameter space as a whole, in the range of parameters here investigated. PMID- 20590300 TI - Modified correlation entropy estimation for a noisy chaotic time series. AB - A method of estimating the Kolmogorov-Sinai (KS) entropy, herein referred to as the modified correlation entropy, is presented. The method can be applied to both noise-free and noisy chaotic time series. It has been applied to some clean and noisy data sets and the numerical results show that the modified correlation entropy is closer to the KS entropy of the nonlinear system calculated by the Lyapunov spectrum than the general correlation entropy. Moreover, the modified correlation entropy is more robust to noise than the correlation entropy. PMID- 20590301 TI - Robust adaptive backstepping control of uncertain Lorenz system. AB - In this paper, a novel robust adaptive control method is proposed for controlling the Lorenz chaotic attractor. A new backstepping controller for the Lorenz system based on the Lyapunov stability theorem is proposed to overcome the singularity problem that appeared in using the typical backstepping control method. By exploiting the property of the system, the resulting controller is shown to be singularity free and the closed loop system is globally stable. Due to unavailability of system states measurement in practice, the controller is selected such that only one system state is needed. To overcome the problem of parameter uncertainty, an additional term to Lyapunov function is added and an identification scheme is adopted to have a negative definite Lyapunov function derivative. The simulation results demonstrate the effectiveness of the proposed controllers and approaches. PMID- 20590302 TI - Outer synchronization of coupled networks using arbitrary coupling strength. AB - This paper mainly studies synchronization between two coupled networks, which is called "outer synchronization." On the basis of Lyapunov function approach, we prove that for networks with balanced structure topology, outer synchronization can be asymptotically reached by using arbitrary coupling strength. We employ a concept which arises in studying the average-consensus problem. Some numerical examples are presented to illustrate the result in the end. The examples indicate that the coupling strength has real influence on the performance of outer synchronization for a short time. The numerical examples also show that the transverse Lyapunov exponent is independent of the value of coupling strength. PMID- 20590303 TI - Shil'nikov chaos and mixed-mode oscillation in Chua circuit. AB - We report experimental observations of Shil'nikov-type homoclinic chaos and mixed mode oscillations in asymmetry-induced Chua's oscillator. The asymmetry plays a crucial role in the related homoclinic bifurcation. The asymmetry is introduced in the Chua circuit by forcing a dc voltage. Then by tuning a control parameter, we observed transition from large amplitude limit cycle to homoclinic chaos via a sequence of mixed-mode oscillations interspersed by chaotic states. We provide experimental evidences that the asymmetry effect can also be induced in the oscillatory Chua circuit when it is coupled with another one in a rest state. The coupling strength then controls the strength of asymmetry and thereby reproduces all the features of Shil'nikov chaos. PMID- 20590304 TI - Exponential lag synchronization for neural networks with mixed delays via periodically intermittent control. AB - In this paper, the exponential lag synchronization for a class of neural networks with discrete delays and distributed delays is studied via periodically intermittent control for the first time. Some novel and useful criteria are derived by using mathematical induction method and the analysis technique which are different from the methods employed in correspondingly previous works. Finally, some numerical simulations are given to demonstrate the effectiveness of the proposed control methods. PMID- 20590305 TI - Map model for synchronization of systems of many coupled oscillators. AB - Synchronization of many coupled oscillators is a generic issue in a wide variety of natural situations. We consider a discrete time map model for the study of such problems. Issues addressed include the effects of noise, oscillation frequency diversity, and network topology, particularly community structure. PMID- 20590306 TI - High-resolution parameter space of an experimental chaotic circuit. AB - A high-resolution codimension-two parameter space showing the abundance of complex periodic structures of an experimental chaotic circuit is reported. Such resolution was propitiated by the use of a 0.5 mV step dc voltage source as one of the control parameters. Those complex periodic structures organize themselves in a period-adding bifurcation cascade that accumulates in a chaotic region. Numerical investigations on the dynamical model were also carried out to corroborate several new features observed in the experimental high-resolution parameter space. PMID- 20590307 TI - Fluctuation theorem, nonlinear response, and the regularity of time reversal symmetry. AB - The Gallavotti-Cohen fluctuation theorem (FT) implies an infinite set of identities between correlation functions that can be seen as a generalization of Green-Kubo formula to the nonlinear regime. As an application, we discuss a perturbative check of the FT relation through these identities for a simple Anosov reversible system; we find that the lack of differentiability of the time reversal operator implies a violation of the Gallavotti-Cohen fluctuation relation. Finally, a brief comparison to Lebowitz-Spohn FT is reported. PMID- 20590308 TI - Estimating parameters by anticipating chaotic synchronization. AB - Anticipating chaotic synchronization based parameter estimation of chaotic system is investigated. We propose a method to estimate the unknown parameters of the interested chaotic system even if only a scalar time series is available. Although the Krasovskii-Lyapunov functional method often results in delay independent stability condition, stability of the synchronization manifold usually relates to time delay. We analyze the stability of anticipating synchronization based parameter estimation numerically. Series of driven systems are used to increase the anticipation time, however, result in longer time to estimate the unknown parameters. These results are also confirmed by numerical simulations. PMID- 20590309 TI - Role of intraspecific competition in the coexistence of mobile populations in spatially extended ecosystems. AB - Evolutionary-game based models of nonhierarchical, cyclically competing populations have become paradigmatic for addressing the fundamental problem of species coexistence in spatially extended ecosystems. We study the role of intraspecific competition in the coexistence and find that the competition can strongly promote the coexistence for high individual mobility in the sense that stable coexistence can arise in parameter regime where extinction would occur without the competition. The critical value of the competition rate beyond which the coexistence is induced is found to be independent of the mobility. We derive a theoretical model based on nonlinear partial differential equations to predict the critical competition rate and the boundaries between the coexistence and extinction regions in a relevant parameter space. We also investigate pattern formation and well-mixed spatiotemporal population dynamics to gain further insights into our findings. PMID- 20590311 TI - Recurrence for quenched random Lorentz tubes. AB - We consider the billiard dynamics in a striplike set that is tessellated by countably many translated copies of the same polygon. A random configuration of semidispersing scatterers is placed in each copy. The ensemble of dynamical systems thus defined, one for each global choice of scatterers, is called quenched random Lorentz tube. We prove that under general conditions, almost every system in the ensemble is recurrent. PMID- 20590310 TI - Chaotic and stable perturbed maps: 2-cycles and spatial models. AB - As the growth rate parameter increases in the Ricker, logistic and some other maps, the models exhibit an irreversible period doubling route to chaos. If a constant positive perturbation is introduced, then the Ricker model (but not the classical logistic map) experiences period doubling reversals; the break of chaos finally gives birth to a stable two-cycle. We outline the maps which demonstrate a similar behavior and also study relevant discrete spatial models where the value in each cell at the next step is defined only by the values at the cell and its nearest neighbors. The stable 2-cycle in a scalar map does not necessarily imply 2-cyclic-type behavior in each cell for the spatial generalization of the map. PMID- 20590312 TI - Stability properties of periodically driven overdamped pendula and their implications to physics of semiconductor superlattices and Josephson junctions. AB - We consider the first order differential equation with a sinusoidal nonlinearity and periodic time dependence, that is, the periodically driven overdamped pendulum. The problem is studied in the case that the explicit time dependence has symmetries common to pure ac-driven systems. The only bifurcation that exists in the system is a degenerate pitchfork bifurcation, which describes an exchange of stability between two symmetric nonlinear modes. Using a type of Prufer transform to a pair of linear differential equations, we derive an approximate condition of the bifurcation. This approximation is in very good agreement with our numerical data. In particular, it works well in the limit of large drive amplitudes and low external frequencies. We demonstrate the usefulness of the theory applying it to the models of pure ac-driven semiconductor superlattices and Josephson junctions. We show how the knowledge of bifurcations in the overdamped pendulum model can be utilized to describe the effects of rectification and amplification of electric fields in these microstructures. PMID- 20590313 TI - Contribution of convection to spatiotemporal stripe patterns formed by Ag and Sb coelectrodeposition. AB - Various spatiotemporal patterns of dark and light stripes are formed on the surface of an electrode put in an electrolyte solution in a Ag and Sb coelectrodeposition system. In this study, we investigate the effect of natural convection of the solution on these spatiotemporal patterns. When the electrode is placed vertically, natural convection generally emerges in the electrolyte solution in the vicinity of the electrode surface during electrodeposition and flows upward along the electrode surface. When convective flow along the electrode surface was eliminated by placing the electrode horizontally, the configuration of the one-directional traveling waves (anisotropic shape) changed to an isotropic shape. This indicates that the formation of an anisotropic shape for one-directional traveling waves is due to upward convective flow along the electrode surface. PMID- 20590315 TI - Topology identification of complex dynamical networks. AB - Recently, some researchers investigated the topology identification for complex networks via LaSalle's invariance principle. The principle cannot be directly applied to time-varying systems since the positive limit sets are generally not invariant. In this paper, we study the topology identification problem for a class of weighted complex networks with time-varying node systems. Adaptive identification laws are proposed to estimate the coupling parameters of the networks with and without communication delays. We prove that the asymptotic identification is ensured by a persistently exciting condition. Numerical simulations are given to demonstrate the effectiveness of the proposed approach. PMID- 20590314 TI - Mechanism, dynamics, and biological existence of multistability in a large class of bursting neurons. AB - Multistability, the coexistence of multiple attractors in a dynamical system, is explored in bursting nerve cells. A modeling study is performed to show that a large class of bursting systems, as defined by a shared topology when represented as dynamical systems, is inherently suited to support multistability. We derive the bifurcation structure and parametric trends leading to multistability in these systems. Evidence for the existence of multirhythmic behavior in neurons of the aquatic mollusc Aplysia californica that is consistent with our proposed mechanism is presented. Although these experimental results are preliminary, they indicate that single neurons may be capable of dynamically storing information for longer time scales than typically attributed to nonsynaptic mechanisms. PMID- 20590316 TI - Chaotic control and synchronization in optical second-harmonic generation with parameter modulating by delay feedback. AB - Chaotic behaviors can be controlled and converted into periodic behaviors by modulating the cavity detuning parameters using delay feedback signal from itself in optical second-harmonic generation (OSHG) system. Numerical simulations show that the period orbit differs on the account of the modulating coefficient and delay time. When the modulating coefficient and delay time are matching, many OSHG systems, whether or not they are in chaos initially, can reach chaotic synchronization if they are driven by a master system and their cavity detuning parameters are varied with the time-delay feedback chaotic signal. Different modulating coefficients with the corresponding minimum delay time are calculated. PMID- 20590317 TI - Common multifractality in the heart rate variability and brain activity of healthy humans. AB - The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems. PMID- 20590318 TI - Irregular behavior in an excitatory-inhibitory neuronal network. AB - Excitatory-inhibitory networks arise in many regions throughout the central nervous system and display complex spatiotemporal firing patterns. These neuronal activity patterns (of individual neurons and/or the whole network) are closely related to the functional status of the system and differ between normal and pathological states. For example, neurons within the basal ganglia, a group of subcortical nuclei that are responsible for the generation of movement, display a variety of dynamic behaviors such as correlated oscillatory activity and irregular, uncorrelated spiking. Neither the origins of these firing patterns nor the mechanisms that underlie the patterns are well understood. We consider a biophysical model of an excitatory-inhibitory network in the basal ganglia and explore how specific biophysical properties of the network contribute to the generation of irregular spiking. We use geometric dynamical systems and singular perturbation methods to systematically reduce the model to a simpler set of equations, which is suitable for analysis. The results specify the dependence on the strengths of synaptic connections and the intrinsic firing properties of the cells in the irregular regime when applied to the subthalamopallidal network of the basal ganglia. PMID- 20590319 TI - A matched filter for chaos. AB - A novel chaotic oscillator is shown to admit an exact analytic solution and a simple matched filter. The oscillator is a hybrid dynamical system including both a differential equation and a discrete switching condition. The analytic solution is written as a linear convolution of a symbol sequence and a fixed basis function, similar to that of conventional communication waveforms. Waveform returns at switching times are shown to be conjugate to a chaotic shift map, effectively proving the existence of chaos in the system. A matched filter in the form of a delay differential equation is derived for the basis function. Applying the matched filter to a received waveform, the bit error rate for detecting symbols is derived, and explicit closed-form expressions are presented for special cases. The oscillator and matched filter are realized in a low-frequency electronic circuit. Remarkable agreement between the analytic solution and the measured chaotic waveform is observed. PMID- 20590320 TI - Global stabilization of fixed points using predictive control. AB - We analyze the global stability properties of some methods of predictive control. We particularly focus on the optimal control function introduced by de Sousa Vieira and Lichtenberg [Phys. Rev. E 54, 1200 (1996)]. We rigorously prove that it is possible to use this method for the global stabilization of a discrete system x(n+1)=f(x(n)) into a positive equilibrium for a class of maps commonly used in population dynamics. Moreover, the controlled system is globally stable for all values of the control parameter for which it is locally asymptotically stable. Our study highlights the difficulty of obtaining global stability results for other methods of predictive control, where higher iterations of f are used in the control scheme. PMID- 20590321 TI - Effect of temperature on precision of chaotic oscillations in nickel electrodissolution. AB - We investigate the effects of temperature on complexity features of chaotic electrochemical oscillations using the anodic electrodissolution of nickel in sulfuric acid. The precision of the "period" of chaotic oscillation is characterized by phase diffusion coefficient (D). It is shown that reduced phase diffusion coefficient (D/frequency) exhibits Arrhenius-type dependency on temperature with apparent activation energy of 108 kJ/mol. The reduced Lyapunov exponent of the attractor exhibits no considerable dependency on temperature. These results suggest that the precision of electrochemical oscillations deteriorates with increase in temperature and the variation of phase diffusion coefficient does not necessarily correlate with that of Lyapunov exponent. Modeling studies qualitatively simulate the behavior observed in the experiments: the precision of oscillations in the chaotic Ni dissolution model can be tuned by changes of a time scale parameter of an essential variable, which is responsible for the development of chaotic behavior. PMID- 20590323 TI - Fractional dissipative standard map. AB - Using kicked differential equations of motion with derivatives of noninteger orders, we obtain generalizations of the dissipative standard map. The main property of these generalized maps, which are called fractional maps, is long term memory. The memory effect in the fractional maps means that their present state of evolution depends on all past states with special forms of weights. Already a small deviation of the order of derivative from the integer value corresponding to the regular dissipative standard map (small memory effects) leads to the qualitatively new behavior of the corresponding attractors. The fractional dissipative standard maps are used to demonstrate a new type of fractional attractors in the wide range of the fractional orders of derivatives. PMID- 20590322 TI - Suppression and generation of rhythms in conjugately coupled nonlinear systems. AB - We explore two diametrically opposite phenomena provoked by conjugate coupling in nonlinear systems. The first effect, known as amplitude death, is observed when the two uncoupled systems are located in the oscillatory regime. In the presence of an appropriate coupling term the oscillatory behavior in both the systems vanishes. This amplitude death is found to persist for nonidentical oscillators, exhibiting different dynamics. In contrast, when the two uncoupled systems are located in the quiescent domain (fixed point behavior), suitable conjugate coupling seems to be capable of generating rhythms in the two systems. Similar to its amplitude death counterpart, induction of rhythms/oscillations is also observed for nonidentical systems. We demonstrate the phenomenon of amplitude death and oscillation generation by numerically studying two different systems, namely, an electrochemical corrosion model and the Hodgkin-Huxley model for neuronal spiking. PMID- 20590324 TI - Inhomogeneity of epidemic spreading. AB - In this study, we use the characteristic infected cluster size to investigate the inhomogeneity of the epidemic spreading in static and dynamic complex networks. The simulation results show that the epidemic spreads inhomogeneously in both cases. Also, the inhomogeneity of the epidemic spreading becomes smaller with increasing speed of moving individuals and almost disappears when the speed is high enough. PMID- 20590325 TI - A lattice Boltzmann model for the Burgers-Fisher equation. AB - A lattice Boltzmann model is developed for the one- and two-dimensional Burgers Fisher equation based on the method of the higher-order moment of equilibrium distribution functions and a series of partial differential equations in different time scales. In order to obtain the two-dimensional Burgers-Fisher equation, vector sigma(j) has been used. And in order to overcome the drawbacks of "error rebound," a new assumption of additional distribution is presented, where two additional terms, in first order and second order separately, are used. Comparisons with the results obtained by other methods reveal that the numerical solutions obtained by the proposed method converge to exact solutions. The model under new assumption gives better results than that with second order assumption. PMID- 20590326 TI - Microscopic realization of cross-correlated noise processes. AB - We present a microscopic theory of cross-correlated noise processes, starting from a Hamiltonian system-reservoir description. In the proposed model, the system is nonlinearly coupled to a reservoir composed of harmonic oscillators, which in turn is driven by an external fluctuating force. We show that the resultant Langevin equation derived from the composite system (system+reservoir+external modulation) contains the essential features of cross correlated noise processes. PMID- 20590328 TI - Parameter mismatches and oscillation death in coupled oscillators. AB - We use a set of qualitatively different models of coupled oscillators (genetic, membrane, Ca-metabolism, and chemical oscillators) to study dynamical regimes in the presence of small detuning. In particular, we focus on a distinct oscillation quenching mechanism, the oscillation death phenomenon. Using bifurcation analysis in general, we demonstrate that under strong coupling via slow variable detuning can eliminate standard oscillatory solutions from a large region of the parameter space, establishing the dominance of oscillation death. We argue furthermore that the oscillation death dominance effect provides a reliable dynamical control mechanism in the general case of N coupled oscillators. PMID- 20590327 TI - Chaos for cardiac arrhythmias through a one-dimensional modulation equation for alternans. AB - Instabilities in cardiac dynamics have been widely investigated in recent years. One facet of this work has studied chaotic behavior, especially possible correlations with fatal arrhythmias. Previously chaotic behavior was observed in various models, specifically in the breakup of spiral and scroll waves. In this paper we study cardiac dynamics and find spatiotemporal chaotic behavior through the Echebarria-Karma modulation equation for alternans in one dimension. Although extreme parameter values are required to produce chaos in this model, it seems significant mathematically that chaos may occur by a different mechanism from previous observations. PMID- 20590329 TI - Noise-induced switching near a depth two heteroclinic network and an application to Boussinesq convection. AB - We investigate the robust heteroclinic dynamics arising in a system of ordinary differential equations in R(4) with symmetry [Formula in text]. This system arises from the normal form reduction of a 1: squate root of 2 mode interaction for Boussinesq convection. We investigate the structure of a particular robust heteroclinic attractor with "depth two connections" from equilibria to subcycles as well as connections between equilibria. The "subcycle" is not asymptotically stable, due to nearby trajectories undertaking an "excursion," but it is a Milnor attractor, meaning that a positive measure set of nearby initial conditions converges to the subcycle. We investigate the dynamics in the presence of noise and find a number of interesting properties. We confirm that typical trajectories wind around the subcycle with very occasional excursions near a depth two connection. The frequency of excursions depends on noise intensity in a subtle manner; in particular, for anisotropic noise, the depth two connection may be visited much more often than for isotropic noise, and more generally the long term statistics of the system depends not only on the noise strength but also on the anisotropy of the noise. Similar properties are confirmed in simulations of Boussinesq convection for parameters giving an attractor with depth two connections. PMID- 20590330 TI - Introduction to focus issue: genetic interactions. AB - The perturbation of a gene in an organism's genome often causes changes in the organism's observable properties or phenotypes. It is not obvious a priori whether the simultaneous perturbation of two genes produces a phenotypic change that is easily predictable from the changes caused by individual perturbations. In fact, this is often not the case: the nonlinearity and interdependence between genetic variants in determining phenotypes, also known as epistasis, is a prevalent phenomenon in biological systems. This focus issue presents recent developments in the study of epistasis and genetic interactions, emphasizing the broad implications of this phenomenon in evolutionary biology, functional genomics, and human diseases. PMID- 20590331 TI - A systems-biology approach to modular genetic complexity. AB - Multiple high-throughput genetic interaction studies have provided substantial evidence of modularity in genetic interaction networks. However, the correspondence between these network modules and specific pathways of information flow is often ambiguous. Genetic interaction and molecular interaction analyses have not generated large-scale maps comprising multiple clearly delineated linear pathways. We seek to clarify the situation by discerning the difference between genetic modules and classical pathways. We review a method to optimize the discovery of biologically meaningful genetic modules based on a previously described context-dependent information measure to obtain maximally informative networks. We compare the results of this method with the established measures of network clustering and find that it balances global and local clustering information in networks. We further discuss the consequences for genetic interaction networks and propose a framework for the analysis of genetic modularity. PMID- 20590332 TI - Recursive expectation-maximization clustering: a method for identifying buffering mechanisms composed of phenomic modules. AB - Interactions between genetic and/or environmental factors are ubiquitous, affecting the phenotypes of organisms in complex ways. Knowledge about such interactions is becoming rate-limiting for our understanding of human disease and other biological phenomena. Phenomics refers to the integrative analysis of how all genes contribute to phenotype variation, entailing genome and organism level information. A systems biology view of gene interactions is critical for phenomics. Unfortunately the problem is intractable in humans; however, it can be addressed in simpler genetic model systems. Our research group has focused on the concept of genetic buffering of phenotypic variation, in studies employing the single-cell eukaryotic organism, S. cerevisiae. We have developed a methodology, quantitative high throughput cellular phenotyping (Q-HTCP), for high-resolution measurements of gene-gene and gene-environment interactions on a genome-wide scale. Q-HTCP is being applied to the complete set of S. cerevisiae gene deletion strains, a unique resource for systematically mapping gene interactions. Genetic buffering is the idea that comprehensive and quantitative knowledge about how genes interact with respect to phenotypes will lead to an appreciation of how genes and pathways are functionally connected at a systems level to maintain homeostasis. However, extracting biologically useful information from Q-HTCP data is challenging, due to the multidimensional and nonlinear nature of gene interactions, together with a relative lack of prior biological information. Here we describe a new approach for mining quantitative genetic interaction data called recursive expectation-maximization clustering (REMc). We developed REMc to help discover phenomic modules, defined as sets of genes with similar patterns of interaction across a series of genetic or environmental perturbations. Such modules are reflective of buffering mechanisms, i.e., genes that play a related role in the maintenance of physiological homeostasis. To develop the method, 297 gene deletion strains were selected based on gene-drug interactions with hydroxyurea, an inhibitor of ribonucleotide reductase enzyme activity, which is critical for DNA synthesis. To partition the gene functions, these 297 deletion strains were challenged with growth inhibitory drugs known to target different genes and cellular pathways. Q-HTCP-derived growth curves were used to quantify all gene interactions, and the data were used to test the performance of REMc. Fundamental advantages of REMc include objective assessment of total number of clusters and assignment to each cluster a log-likelihood value, which can be considered an indicator of statistical quality of clusters. To assess the biological quality of clusters, we developed a method called gene ontology information divergence z-score (GOid_z). GOid_z summarizes total enrichment of GO attributes within individual clusters. Using these and other criteria, we compared the performance of REMc to hierarchical and K-means clustering. The main conclusion is that REMc provides distinct efficiencies for mining Q-HTCP data. It facilitates identification of phenomic modules, which contribute to buffering mechanisms that underlie cellular homeostasis and the regulation of phenotypic expression. PMID- 20590333 TI - Deep epistasis in human metabolism. AB - We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33,328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing "deep" epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets. PMID- 20590334 TI - Multiple peaks and reciprocal sign epistasis in an empirically determined genotype-phenotype landscape. AB - Insight into the ruggedness of adaptive landscapes is central to understanding the mechanisms and constraints that shape the course of evolution. While empirical data on adaptive landscapes remain scarce, a handful of recent investigations have revealed genotype-phenotype and genotype-fitness landscapes that appeared smooth and single peaked. Here, we used existing in vivo measurements on lac repressor and operator mutants in Escherichia coli to reconstruct the genotype-phenotype map that details the repression value of this regulatory system as a function of two key repressor residues and four key operator base pairs. We found that this landscape is multipeaked, harboring in total 19 distinct optima. Analysis showed that all direct evolutionary pathways between peaks involve significant dips in the repression value. Consistent with earlier predictions, we found reciprocal sign epistatic interactions at the repression minimum of the most favorable paths between two peaks. These results suggest that the occurrence of multiple peaks and reciprocal epistatic interactions may be a general feature in coevolving systems like the repressor operator pair studied here. PMID- 20590335 TI - Simple genomes, complex interactions: epistasis in RNA virus. AB - Owed to their reduced size and low number of proteins encoded, RNA viruses and other subviral pathogens are often considered as being genetically too simple. However, this structural simplicity also creates the necessity for viral RNA sequences to encode for more than one protein and for proteins to carry out multiple functions, all together resulting in complex patterns of genetic interactions. In this work we will first review the experimental studies revealing that the architecture of viral genomes is dominated by antagonistic interactions among loci. Second, we will also review mathematical models and provide a description of computational tools for the study of RNA virus dynamics and evolution. As an application of these tools, we will finish this review article by analyzing a stochastic bit-string model of in silico virus replication. This model analyzes the interplay between epistasis and the mode of replication on determining the population load of deleterious mutations. The model suggests that, for a given mutation rate, the deleterious mutational load is always larger when epistasis is predominantly antagonistic than when synergism is the rule. However, the magnitude of this effect is larger if replication occurs geometrically than if it proceeds linearly. PMID- 20590336 TI - Evolution of a single gene highlights the complexity underlying molecular descriptions of fitness. AB - Evolution by natural selection is the driving force behind the endless variation we see in nature, yet our understanding of how changes at the molecular level give rise to different phenotypes and altered fitness at the population level remains inadequate. The reproductive fitness of an organism is the most basic metric that describes the chance that an organism will succeed or fail in its environment and it depends upon a complex network of inter- and intramolecular interactions. A deeper understanding of the quantitative relationships relating molecular evolution to adaptation, and consequently fitness, can guide our understanding of important issues in biomedicine such as drug resistance and the engineering of new organisms with applications to biotechnology. We have developed the "weak link" approach to determine how changes in molecular structure and function can relate to fitness and evolutionary outcomes. By replacing adenylate kinase (AK), an essential gene, in a thermophile with a homologous AK from a mesophile we have created a maladapted weak link that produces a temperature-sensitive phenotype. The recombinant strain adapts to nonpermissive temperatures through point mutations to the weak link that increase both stability and activity of the enzyme AK at higher temperatures. Here, we propose a fitness function relating enzyme activity to growth rate and use it to create a dynamic model of a population of bacterial cells. Using metabolic control analysis we show that the growth rate exhibits thresholdlike behavior, saturating at high enzyme activity as other reactions in the energy metabolism pathway become rate limiting. The dynamic model accurately recapitulates observed evolutionary outcomes. These findings suggest that in vitro enzyme kinetic data, in combination with metabolic network analysis, can be used to create fitness functions and dynamic models of evolution within simple metabolic systems. PMID- 20590340 TI - Opioids in middle eastern populations. AB - Morphine is one of the more ancient medicines known, yet the global access to this opioid is still severely limited. In spite of the fact that strong networks for national, regional and global care have been emerging, the overall situation of pain management, in general, and in cancer patients in specific, remains of great concern; when we examine the availability of pain relief drugs in Middle Eastern countries. The data presented in this abstract rely on the INCB annual reports. Consumption of Morphine. In the USA the consumption is on the rise and has reached over 76 mg/capita in the year 2007 (the global mean is 5.57 mg/capita). In Israel the consumption of morphine in 2007 is similar to that in 2004, a little above 3.0 mg/capita. In Cyprus during the year 2004-2007 the consumption was at about 2.8 mg/capita. In Jordan, morphine consumption has been on the rise since 2006 and is at about 2.0 mg/capita. In Lebanon, morphine consumption has been at a steady state (1.0 mg/capita) for the period 2004-2007. In Turkey, the consumption of morphine has been fluctuating at doses about 0.1 mg/capita fort the period 2004-2007. In Saudi Arabia, the consumption of morphine has been at very low doses of about 0.05 mg/capita for the same time period. In Egypt, the doss of consumption were fluctuating between 0.01-0.14 mg/capita during the years 2004-2007. When comparing the quantities of consumption in the various Middle Eastern countries with that in the United States (in year 2007), it became apparent that in the USA the consumption of morphine is: 10 times that in Israel; 27 times that in Cyprus; 38 times that in Jordan; 69 times that in Lebanon; 150 times that in Saudi Arabia; 447 times that in Turkey; 633 times that in Egypt. It is nowadays clear that the medial use of opioid drugs is indispensable for the relief of pain and suffering; and most developing countries use very small amounts of morphine. PMID- 20590337 TI - On the possible role of robustness in the evolution of infectious diseases. AB - Robustness describes the capacity for a biological system to remain canalized despite perturbation. Genetic robustness affords maintenance of phenotype despite mutational input, necessarily involving the role of epistasis. Environmental robustness is phenotypic constancy in the face of environmental variation, where epistasis may be uninvolved. Here we discuss genetic and environmental robustness, from the standpoint of infectious disease evolution, and suggest that robustness may be a unifying principle for understanding how different disease agents evolve. We focus especially on viruses with RNA genomes due to their importance in the evolution of emerging diseases and as model systems to test robustness theory. We present new data on adaptive constraints for a model RNA virus challenged to evolve in response to UV radiation. We also draw attention to other infectious disease systems where robustness theory may prove useful for bridging evolutionary biology and biomedicine, especially the evolution of antibiotic resistance in bacteria, immune evasion by influenza, and malaria parasite infections. PMID- 20590341 TI - The global experience of cancer pain. AB - Pain is a significant problem in patients with cancer. Pain occurs in approximately 50% of patients at some point during the disease process and in up to 75% of patients with advanced cancer. Total pain impacts quality of life domains including physical, psychological, social, and spiritual realms. Unfortunately, pain is underappreciated and undermanaged throughout the world. Lack of knowledge among healthcare professionals, inadequate pain assessment, fears of addiction, and beliefs that pain is an inevitable component of cancer are common barriers. Education about comprehensive pain assessment and optimal management strategies and discussions about belief systems regarding pain can assist to bridge the gap between suffering and comfort. Self-report is the gold standard for pain assessment. Gathering information about the location(s), intensity, quality and temporal factors is essential. Intensity should be quantified on a rating scale to determine the amount of pain and the degree of relief from interventions. Quality can be used to diagnose the specific pain syndrome. Temporal factors provide input about how the pain is experienced over time and can offer input into the pain management plan of care. For patients who cannot self-report pain, non-verbal assessment tools are available to aid in assessment. The World Health Organization's Analgesic Ladder provides a template for the management of cancer pain. For step 1, pain can be managed with nonsteroidal anti-inflammatory drugs (NSAIDS) and other nonopioid analgesics. As pain persists or increases, step 2 involves managing pain with select opioids for mild to moderate pain along with NSAIDS and nonopioid analgesics. Step 3 of the ladder is applicable to many cancer pain syndromes, and includes opioids for moderate to severe pain in conjunction with NSAIDS and nonopioids. This 3 step approach can be 80-90% effective. This polypharmaceutical employed with behavioral complimentary techniques are often employed to interrupt pain along the physiological pathways during transduction, transmission, perception, and modulation. Severe cancer pain that is not managed with the Step 3 approach, deserves special attention and unique strategies for control. When pain control is inadequate or if side effects are intolerable, a change of opioid or a change in the route of administration is recommended. Intraspinal analgesics can be trialed in patients who have intractable pain or intolerable side effects with systemic opioids. This route is especially helpful in neuropathic pain syndromes located at the trunk level or below. Opioid doses in all patients with intractable pain should be titrated judiciously for optimal relief with a balance of toxicity management. Other strategies for intractable pain should be investigated including nerve blocks and neuroablation. The overall goal for patients is to attain comfort with minimal side effects and optimal quality of life. PMID- 20590342 TI - Using leadership and advocacy to improve cancer pain management--based on a presentation at the cancer pain, suffering and spirituality course. AB - Being a leader is not dependent on a title and, in fact, every oncology nurse is a clinical leader. Building on skills in caring for patients, oncology clinicians and nurses use their knowledge and skills to: advocate for patients; initiate performance improvement projects; develop new services for patients and families; ensure quality and safety of care; influence health policy. Because of oncology clinicians and nurses closeness to patients and families in all settings, they know where the barriers to excellence are in organizations. This session will provide an overview of leadership skills and how nurses in particular can use their expertise as clinicians to improve the care delivery in their organizations and communities. PMID- 20590343 TI - Regulatory barriers for adequate pain control. AB - In 1961 the "Single Convention on Narcotic Drugs" was adopted by the United Nations to explicitly address the need for narcotic drugs to curtail suffering and keep the distribution of these drugs in the control of health professionals. Fifty years later, neither goal has been reached for a variety of reasons. Governments have avoided putting in place systems to assure adequate supplies to relieve the suffering of those with severe pain, drug enforcement agencies maintain restrictive regulations and physicians are intimidated by threats of legal action if their prescribing patterns do not conform to arbitrary standards. There is a shortage of pain control consultants and the training for most health care providers is deficient when it comes to the management of chronic pain. Some of the regulatory barriers have been successfully addressed through advocacy efforts and the expertise deficiencies improved through targeted educational programs. PMID- 20590344 TI - Advanced care planning--empowering patients for a peaceful death. AB - In the early 1900's, Americans had a life expectancy of about 50 years. Childhood mortality was very high and an adult who lived into their sixties was considered to be doing pretty well. Prior to the advent of different types of antibiotics, people would die quickly of infectious disease or accidents and medicine only really focused on caring and comfort. Since then, there has been a shift in medicines focus. New science, technology and communications have shifted the way Americans treat incurable diseases and have promoted the idea of aggressive fighting as well as to keep patients alive at any costs. The internet has allowed easy access for patients to do on-line research and to know the treatments for diseases and the availability of trials. This has promoted the idea that every disease or cancer is curable if the patient does exactly as the internet says. It has hindered the idea of compassionate care and dying with dignity so that a patient can stay alive at all costs, even in a vegetative state. In the last two decades, there has been a significant expansion of palliative and supportive care services in the United States. This has including the development of a specialty for palliative care medicine with a board certification in hospice and palliative medicine. A challenge to the field has been the reluctance of physicians to request palliative care consults in a very timely manner as well as relinquish care of their patients. A common occurrence in the United States, at many cancer centers, is the treatment of chemotherapy and radiation up until the day before a patient dies. At this point, the physician ends up throwing up his or her hands with nothing left to offer the patient or its family. However, what we have been finding is that presently there are now many oncologists who are willing to refer patients to palliative care for specific management of difficult pain control issues. At the Moffitt Cancer Center, we have a Palliative Care consulting service along with a Palliative Care Fellowship program where we work with cancer teams to provide resources to them when they are running into difficulties with their patients. Typically, we step in when first line treatments have failed, symptoms have shown no signs of decrease, or when the primary teams have exhausted their standard management options. Our hope is for the primary care teams to be able to manage basic symptoms themselves and only call on the Palliative Care team when they have surpassed their comfort zone. For example, the Palliative Care team would step in if a patients dosage of medication was out of a primary teams spectrum. Other uses of the Palliative Care team include having the end of life discussion with the patients to find out what their expectations are of their treatment, what their concerns are and what their requests are. Normally treating primary teams are very uncomfortable in having this discussion with their patients due to the feeling that they are giving up hope or the fact that they are letting patients know that the end of the road is near. The Palliative Care team can then be called upon to come in and transfer the care from the primary team to the "death team". At Moffitt we have instituted a number of strategies to make this transition acceptable and more beneficial for the patients. One of the strategies that we used is an Advanced Care Plan. By having a consultation at the time when the patient is diagnosed, we are able to speak with them about what it is that they see in terms of what would be acceptable to them. We use the Project Grace Advance Care Plan which was developed by a physician and is very simple to understand. With this tool, we are able to bring up the discussion while trying to focus in on the patients spirituality and the coping mechanism as the cancer patient. This allows the conversation of end of life treatment preferences and what the patients typical desire is for life sustaining measures. PMID- 20590345 TI - Clinical aspects of pharmacogenetics of pain and co-morbidities of emotional distress. AB - The majority of patients treated for cancer will have pain at some point in their journey. It will be due to the disease (e.g. bone metastasis, fracture, organ invasion) or from iatrogenic causes (chemotherapy, surgery or radiation). A large number of patients will also have depression. Since pain and depression share common biological pathways and even neuro-transmitters it is not surprising that a comorbidity of pain is depression. It has already been reported that patients in severe pain are 4 times less likely to respond to therapy for depression. In recent years, especially in the era of molecular biology and post-genomic a wealth of data in the arena of pharmacogenetics/genomics has shed more light on cancer related symptoms such as pain and related them to the cytokine pathways, especially the interleukins and tumor necrosis factor (TNF). When we remember that the synonym for TNF is "cachectin" it is no wonder patients feel awful when there is active disease and the body trying to mount a response. Neuroendocrine, immunomodulatory and inflammatory pathways are likely important in the pathophysiology of pain and depression. These realizations are in addition to a greater understanding of afferent pathways for pain perception, of the multiple opioid receptors, the effects of hormones and catechol metabolism and other transmitters. Moreover we already have a more complete under-standing of drug metabolism, especially of the opioids, the back bone of all pain treatment. There are a number of single nucleotide polymorphisms (SNPs) in the genes important for drug metabolism such as CYP2D6, a cytochrome responsible for about 25% of all drugs. There are about 90 variants already reported and rapid and slow metabolizers need very different doses of codeine or morphine. We are entering an era of having the capability to develop personalized treatment for our patients nociceptive pain, neuropathic pain and depression. The convergence of new knowledge in the molecular biology and pharmacogenetic era should allow us to treat our patients suffering with a resultant increased quality of life even while we strive to cure them of their malignancy. PMID- 20590346 TI - Spiritual pain and suffering. AB - Spiritual pain/suffering is commonly experienced by persons with life-limiting illness and their families. Physical pain itself can be exacerbated by non physical causes such as fear, anxiety, grief, unresolved guilt, depression and unmet spiritual meets. Likewise, the inability to manage physical pain well can be due to emotional and spiritual needs. This is why a holistic, interdisciplinary assessment of pain and suffering is required for each patient and family. The mind, body and spirit are understood in relationship to each other and, in those cases, in relationship to a deity or deities are important to understand. Cultural interpretations of pain and suffering may conflict with the goals of palliative care. Understanding the spiritual framework of the patient and family can help to assure that the physical and spiritual suffering of the patient can be eliminated to provide a peaceful death. Spiritual practices may help in the management of physical pain. PMID- 20590347 TI - Practical approaches to spiritual pain. AB - Spiritual pain/suffering is commonly experienced by persons with life-limiting illness and their families. Physical pain itself can be exacerbated by non physical causes such as fear, anxiety, grief, unresolved guilt, depression and unmet spiritual meets. Likewise, the inability to manage physical pain well can be due to emotional and spiritual needs. This is why a holistic, interdisciplinary assessment of pain and suffering is required for each patient and family. The mind, body and spirit are understood in relationship to each other and, in those cases, in relationship to a deity or deities are important to understand. Cultural interpretations of pain and suffering may conflict with the goals of palliative care. Understanding the spiritual framework of the patient and family can help to assure that the physical and spiritual suffering of the patient can be eliminated to provide a peaceful death. Spiritual practices may help in the management of physical pain. PMID- 20590348 TI - Beyond quality of life: the meaning of death and suffering in palliative care. AB - The majority of patients treated for cancer will have pain at some point in their journey. Suffering and death are common events in cancer patients. Palliative care has been very successful in reducing the discomfort caused by physical pain, but does not have the means to address the questions related to the meaning of suffering and death. The soothing of physical pain has helped highlighting other forms of pain, such as spiritual and existential pain, that uniformly accompany the terminal phase of the disease. Health care providers should be able to identify existential and spiritual pain for several reasons. First, because misdiagnosing these conditions may lead to inappropriate use of opioids and sedatives and may deprive both the patient and the patients family of the experience of death as an essential and irreplaceable experience of life. Second, because spiritual and existential pain may be addressed by properly trained professionals that should be involved in the management of the patients when needed. Chaplains and spiritual directors have no lesser role in the management of a patient than a cardiologist, a surgeon or a psychiatrist. Third because clinical scientists cannot close their eyes in front of one of the most common human experiences falling under their domain. Lack of training and of full understanding is a lame excuse for skirting the suffering of a person dying under our eyes. Health care providers unwilling or unable to abandon their areas of comfort and to embrace new and risky experiences are a liability for themselves, for their patients, and for the society they serve. Both spiritual and existential pain address the basic questions of human consciousness: while are we alive? Why do we die? Spiritual pain is most commonly experienced by a person who has a religious or otherwise sense of transcendence and may be helped by a hospital care trained chaplain. Existential pain is more typical of a person uninterested in a transcendent context and may be more challenging to address in the health care context. Though both may produce emotional pain, neither is by itself a form of emotional pain and cannot be fully cared for by a counselor. The clinical definition of spiritual and existential pain is evolving and so is its treatment. Classical clinical trials have little to offer for these conditions. Qualitative research in its various forms, including open ended questions, content analysis and mainly personal narrative are the most promising forms of research to comprehend spiritual and existential pain. PMID- 20590349 TI - Religion, medicine and spirituality: what we know, what we don't know and what we do. AB - Religion and spirituality have been linked to medicine and to healing for centuries. However, in the early 1900's the Flexner report noted that there was no place for religion in medicine; that medicine was strictly a scientific field, not a theological or philosophical one. In the mid to the latter 1900's there were several lay movements that started emphasized the importance of religion, spirituality and medicine. Lay religious movements found spiritual practices and beliefs to be important in how people cope with suffering and find inner healing even in the midst of incurable illness. The rise of Complementary and Alternative Medicine as well as the Hospice movements also influenced attention on the spiritual aspect of medicine. The Hospice movement, founded by Dr. Cecily Saunders, described the concept of "total pain"--i.e. the biopsychosocial and spiritual aspects of pain and suffering. Since the 1960's there has been increased research done in the area of religion and health and spirituality and health. Most of the studies are association studies which demonstrate and association of religious or spiritual beliefs and practices and some healthcare outcomes. More recently, studies on meditation have demonstrated significant improvement in health care outcomes and suggest meditation as a therapeutic modality. There are also numerous surveys that demonstrate patient need for having spirituality integrated into their care. Finally, a recent study demonstrated that patients with advanced illness who have spiritual care have better quality of life, increased utilization of hospice and less aggressive care at the end of life. In spite of all these studies, we still do not have a biological evidence base for mechanisms of beliefs and practices. There is considerable controversy over whether spirituality and religion can or even should be measured as criteria for integration into clinical care. Many believe that healthcare professionals have an ethical obligation to attend to all dimensions of a person's suffering, including the psychosocial as well as the spiritual and that ethical obligation is sufficient to require integration of spirituality into clinical care. Over the last twenty years, there has been an increase in the number of required courses in spirituality and medicine in US medical schools giving rise to a new field of medicine. In February of 2009, a national consensus conference developed spiritual care guidelines for interprofessional clinical spiritual care. These guidelines as well as the educational advances, research and ethical principles have supported the newly developing field of spirituality and health. PMID- 20590350 TI - Formal and informal spiritual assessment. AB - Spirituality is increasingly recognized as an essential element of health. A novel model of interprofessional spiritual care was developed by a national consensus conference of experts in spiritual care and palliative care. Integral to this model is a spiritual screening, history or assessment as part of the routine history of patients. Spiritual screening can be done by a clinician on an intake into a hospital setting. Clinicians who make diagnosis and assessments and plans, and make referrals to appropriate experts do spiritual histories. In spiritual care, board certified chaplains, spiritual directors and pastoral counselors are the typical spiritual care referrals. Board certified chaplain do a spiritual assessment that is a more detailed assessment of religious and spiritual beliefs and how those impact care or patient's healthcare decision making. There are several screening and history tools. One history tool named FICA, was developed by a group of primary care physicians and recently validated at study at the City of Hope. This tool is widely used in a variety of clinical settings in the US and Canada. The spiritual history tools allow the clinician the opportunity to diagnose spiritual distress or identify patients' spiritual resources of strength and then integrate that information into the clinical treatment or care plan. PMID- 20590351 TI - My illness, myself: on the secrecy of shame. AB - Research has shown that the experience of being diagnosed with cancer has a negative psychosocial impact on patients and their families, often resulting in distress, and numerous practical and relationship challenges. Men with prostate cancer and their partners face special challenges. A range of symptoms that result from monitoring patients and side effects of treatment may reverse the quality of life and intimate relations between patient and partner. However, patients often are reluctant to bring up their distress about the symptoms, leading to an underestimation and reduction in optimal symptom control. As a result of their illness, chronically-ill male patients often experience elevated levels of stress, daily activities are often limited, they are frustrated about the unpredictable course of the illness and its symptoms, and are immersed in fears about their present and future social identity. Most of them avoid disclosure about their illness--when and where possible--and place great importance on sustaining a normal life. Factors related to limiting disclosure include men's low perceived need for support, fear of stigmatization, the need to minimize the threat of illness to aid coping, practical necessities in the workplace, and the desire to avoid burdening others. This paper contributes to an understanding of the complex issues of disclosure related to prostate cancer patients and raises issues about how best to be helpful, within their cultural and social framework. It also deals with feelings of shame, guilt and inadequacy as the cause--or consequence--of concealing the illness. The oral presentation will use a clinical example of secrecy and the subsequent conflicts and quandaries of a religious person diagnosed with advanced prostate cancer. Dilemmas of shame, disclosure and guilt will be the focus of the discussion. PMID- 20590352 TI - Beyond pain--the search for hope in the patient's journey. AB - Hope is the foundation of the cancer patients' world and it is when the darkness is most profound that hope emerges as the true reality. Hope remains the patients' inner strength, a dynamism that grows more powerful even as the physical body weakens. We humans are always hoping for something and The Hope System addresses all levels of the entire cancer experience: physical, emotional, psychological and spiritual. By systematically learning how to recognize and honor patients' hopes, each of us can support him/her from first diagnosis to last breath in a way that is healing and positive for all. Utilizing this simple, powerful tool enables us to tap into the patient's ever changing reality, the role hope plays in one's life while confronting one's mortality, and be able to listen, hear and accompany them each step on their final life into death journey. PMID- 20590353 TI - Bring about benefit, forestall harm: what communication studies say about spirituality and cancer care. AB - Technological advances in medicine allow health care providers to diagnose diseases earlier, diminish suffering, and prolong life. These advances, although widely revered for changing the face of cancer care, come at a cost for patients, families, and even health care providers. One widely cited consequence of better diagnostics and improved treatment regiments is the sense that there is always one more test or therapy available to extend life. Such an approach to cancer care can prove detrimental to patients? healing. In addition, these new tests and treatments further focus attention on the body as the site of healing and cure while downplaying other aspects of health. The absence of psychological, social, and spiritual care from a patient's cancer care plan compromises healing and makes palliative and end of life care more complicated. In this essay, I discuss the tensions that exist between contemporary cancer care and spirituality and use Communication Studies scholarship to navigate the challenges of integrating a patient's religious or spiritual beliefs into their cancer treatment and care. In addition to discussing the challenges of communicating about sensitive topics such as illness, spirituality, and dying, this article uses narrative examples from a comprehensive cancer center and a hospice (both in the United States) to understand how people with cancer and other terminal illnesses communicate their spirituality and how these conversations influence health care choices and provide comfort. By understanding how patients communicate about topics such as the meaning of life, quality of life, dying and death, providers are better equipped to offer care that is consistent with a patient's beliefs and life goals. This approach maintains that communication is more than a means of transferring information, but is constitutive. By understanding that communication creates our lives and shapes our worlds, lay and professional caregivers can meet patients where they are spiritually, emotionally, and socially and offer effective care that is culturally situated. For many in Muslim societies, a cancer diagnosis is Divine fate. Understanding a cancer diagnosis as destiny offers comfort to some, yet cancer patients and their family members may experience isolation because of the stigmas associated with the disease. This double-bind can lead to spiritual or existential crises, which draws further attention to the need for effective spiritual care that ultimately fosters patient and family healing whether or not a cure is possible. Bringing together various approaches to communicating about diverse spiritual and religious ideas may allow for enhanced comprehensive cancer care. PMID- 20590354 TI - Researching the meaning of life: finding new sources of hope. AB - The purpose of the paper is to discuss means of assisting terminally ill patients in seeking for sources of meaning and hope, alongside the acknowledgment that their lifespan is short.Psycho-spiritual aspects make a substantial component patients suffering from incurable illness have to deal with. Evaluating and mapping the causes and expressions of psychological--spiritual suffering may assist in tailoring appropriate strategies of distress relief. Therefore, interventions should be given in accordance with their specific focus of difficulties, as well as with wishes and needs. Appropriate interventions in palliative psychotherapeutic rapport are inspired by identifying new sources for meaning in current life (sometimes, aided by past experiences or future visions). Reinforcing sources for meaning may attempt in providing patients amongst:- equilibrium, between suffering and sorrow (which sometimes take over the patient's world), and on the other hand, new experiences, sense of satisfaction and fulfillment. Individual's acknowledgment that he is not completely withdrawn from the circle of life, and yet significance and fulfillment in life still exists. For a holistic meaning ? centered intervention it is advisable to simultaneously integrate two central axes: the existential analysis, inspired by concepts driven from Frenkl's Logotherapy, such as freedom of choice, personal responsibility, inner truth, hope and transcendentalism; the operative axis, enhancing meaning and hope by assisting patient's wishes come true. Patients are aware, many times, that those wishes may be their last one, therefore perceive their fulfillment as crucial for their sense of meaning. Moreover, those wishes may elevate patient and family's spirit and reduce risk of demoralization. Whereas existential--spiritual interventions are recommended to be given by qualified professional therapists, the operation of fulfilling wishes is feasible by everyone, from family members to multi-disciplinary staff. Case illustrations for meaning--centered interventions will be discussed in the course of the paper. Cultural and traditional differences within the Israeli society, expressed in themes of work with patients, will lead to the conclusion, that there are many creative ways for researching meaning of life and sources for hope. PMID- 20590355 TI - Medicine and spirituality: a personal adventure. AB - Perhaps more than any other profession medicine gives power to its practitioners. "It is difficult to remain emperor in front of a physician" claims the Roman emperor Adrian in his memories. When I found myself as a doctor endowed with the power of telling people what was good for them I realized that I had become the arbiter of normality, that I could have told people how to live there lives, without having any idea of how living my own. While I cannot identify a single experience as a turning point, certainly an accumulation of experiences, personal and professional contributed to the abandonment of this facade and the embracement of the spiritual dimension in the practice of medicine. Like Chesterton describes in his book 'Orthodoxy' the discovery of the spiritual dimension in medicine was a long pigrimage home, toward myself, to learn how to love and dignify myself. PMID- 20590356 TI - Coping with stress in patients with advanced cancer. AB - The incidence and mortality of cancer are increasing day to day. Advanced cancer is cancer that has grown beyond the organ where it first started. Often it has spread widely throughout the body. In advanced cancer when cure is impossible, symptoms should be the focus of attention. Having advanced cancer can bring anxiety and uncertainty to life of patients. Most people who have survived cancer and completed their treatment will say that they live with the underlying fear that their cancer will return. Some people with advanced cancer are living longer and with better quality of life (QOL). Each person with advanced cancer has unique experience. Advanced cancer is not the same for everyone; it behaves differently depending on what patients' primary cancer diagnosis have been. Symptoms then get worse and treatments are needed to help them to control. These symptoms can often be treated. Likewise, each person faced with recurrent cancer will cope differently too. Assessing and understanding the impact of cancer on patients is, therefore, very important for providing the appropriate care and for improving patients' QOL. Understanding the reasons why some individuals become depressed and faced with some problems in advanced cancer has become an increasingly important area in palliative care. By interest in end of life care, clinicans, nurses, social workers, psychologists, and researchers alike have begun to focus their attention on identifying factors that might facilitate coping with advanced cancer. The goals of this study was to examine cancer related stressors and how patients coping with them. For understanding cancer related stressors and coping patterns of patients with advanced cancer current literature has been examined. In this study the specific symptoms and concerns which are faced by advanced cancer patients has been assigned shortly on a priori basis in to the dimensions of physicial symptomps, psychological symptoms, social concerns and, existential issues. Coping with this stressors some useful coping strategies (problem focused and emotional focused approach) are suggested in this study. Framework which is developed by this study can be useful for understanding cancer related stressors, some interventions to assist cancer patients to manage symptoms (pain, fatigue) and coping strategies for health care staff who worked with advanced cancer patients. Health care staff who are aware of the common stressors in advanced cancer, palliative care and end of life care may identify more readily the need for support and assistance with coping strategies, thus improving the overall QOL of their patients. Providing psychological and social support requires interdisciplinary collaboration guided by a perspective of QOL in palliative care. PMID- 20590357 TI - Historical perspectives and trends in the management of pain for cancer patients in oman. AB - INTRODUCTION: Sultanate of Oman is the second largest country in the Gulf, with a population of 2,867,428 (2008) of which 35.2% is under 15 years and only 3.7% above 65 years. Incidence of newly diagnosed cancers is also the second highest in the Gulf with 11%. Research conducted between 1997-2007 revealed that the most frequent cancers in males: stomach 10%, non-Hodgkins lymphoma 8.6% and prostate 7% while in females: breast 18.9%, thyroid 8.3% and cervix uteri 6.5%. A population-based registry was established in 1996 to compile an accurate database and monitor cancer trends. There is a rigorous follow up of reported cases. Unfortunately most patients report at the hospitals in advanced stages which complicate pain management. All treatment modalities of cancer are available in Oman at the two centers, Royal Hospital and SQUH. There is a continuous effort to develop national educational guidelines, protocols for cancer treatment, palliative care and pain management (PM). HISTORICAL PERSPECTIVES AND TRENDS IN THE MANAGEMENT OF PAIN: In 1970s Omanis used traditional medicine, wassam (moxibustion), to treat pain. In 1988 severe pain was treated in hospitals with intramuscular opioid, whenever necessary (PRN). 1989 SQUH approved use of both parenteral and oral narcotics, received its first consignment, and started PM. The Ministry of Health (MOH) was concerned with possible misuse and for 8 years, thereafter, SQUH was the only hospital allowed to import, stock, prescribe and dispense oral narcotics. Legal requirement to obtain opioids in Oman involves MOH and World Health Organization (WHO) and there is a control as to who can prescribe for both inpatient and outpatient. The drugs available to control pain include non opioids, weak opioids, but the only strong opioids used for severe cancer pain are morphine and Fentanyl. This is complemented with adjuvant drugs. We use the "WHO Ladder" to guide us in the management of pain. Three different cases have been presented to see how PM of cancer patients has evolved from using only non-opioid in 1993, to using intramuscular pethidine in 1995, then to using morphine with adjuvants in 1999. Referral of patients to the PM Team has improved the pain control and at present even without referral, pain is controlled more effectively. CONCLUSION: There is no doubt that the Sultanate of Oman has progressed tremendously since 1970. The Government is working very hard and is taking major steps to improve cancer care in order to meet the International Bench Mark. Each 5 year plan focuses on actual needs. One of the important needs that have been addressed is the management of pain which has significantly improved. Factors that have improved PM in Oman include the introduction of the PM Teams, training of Nurses and Doctors, follow up of the PM services in the clinical areas, authorizing MOH hospitals to use oral opioids, opening of the National Oncology Centre with Radiation Therapy, inter institutional discussions and development of guidelines, implementation of WHO Guidelines on PM and audits, peer reviews and research. PMID- 20590358 TI - Pain relief is a human right. AB - For centuries, medical and surgical treatment has emphasized saving the life of the patient rather than ameliorating the patient's pain, particularly when there were few options for the latter. Today at the dawn of the 21st century, the best available evidence indicates a major gap between an increasingly understanding of the pathophysiology of pain and widespread inadequacy of its treatment. Epidemiologic evidence has proven that chronic pain is a widespread public health issue. Studies of cancer patients' pain control consistently reveal that up to half of patients receive inadequate analgesia and 30% do not receive appropriate drugs for their pain. Equally, for patients suffering HIV/AIDS, 60%-100% will experience pain at some stage in their illness. In the developed world, this gap has prompted a series of declarations and actions by national and international bodies advocating better pain control. One response to the worldwide undertreatment of pain has been to promote the concept that pain relief is a public health issue of such critical importance as to constitute an international imperative and fundamental human right. The importance of pain relief as the core of the medical ethic is clear. Pain clinicians promote the status of pain management beyond that of appropriate clinical practice or even an ethic of good medicine. They advocate a paradigm shift in the medical professions' perspective on pain management, from simply good practice to an imperative founded on patient rights. There is a need to promote policies which create conditions where human beings can bear even incurable illnesses and death in a dignified manner. This must help health professionals or lay groups to initiate a powerful agenda to reform local statutes. The essential components of such legislation are: 1. Reasonable pain management is a right. 2. Doctors have a duty to listen to and reasonably respond to a patient's report of pain. 3. Provision of necessary pain relief is immune from potential legal liability. 4. Doctors who are notable or willing to ensure adequate analgesia must refer to a colleague who has this expertise. 5. Pain management must be a compulsory component of continuing medical education. For too long, pain and its management have been prisoners of myth, irrationality, ignorance, and cultural bias. We are confident that the Pain Relief and Palliative Care Working Group under the auspices of the Lebanese Cancer Society is the main promoter of Palliative Care in Lebanon whose main goal is to relieve suffering and improve quality of life of the cancer patients, and advocate pain relief as a human right. PMID- 20590359 TI - Pain coping behaviors of saudi patients suffering from advanced cancer: a revisited experience. AB - BACKGROUND: Cancer is one of the major health problems throughout the world. The number of cancer patients is increasing, out of the estimated nine million new cancer cases every year, more than half are in developing countries. The majority of these patients are incurable by the time their disease is diagnosed. Therefore, cancer mortality is expected to continue to rise in those regions of the world (WHO, 2002). In Saudi Arabia, the latest report from the Saudi Cancer Registry SCR for 2004 registered 9,381 new cases, of these cases 7,138 were Saudis. The crude incidence rate CIR of all cancers among Saudis was 41.9/100,000. The total number of adult cancer incidence cases reported was 8595, and for children were 713 cases (NCR, 2004). The most common feared symptom encountered in advanced cancer is pain. Through their perpetual encounter with pain, advanced cancer patients usually maintain different coping behaviors. Internationally speaking, there are limited researches and investigations that deal with cancer pain, and the importance of using adaptive coping behaviors to control it. In Saudi Arabia, specifically, pain coping behaviors has never been assessed or discussed before, so is the impact of cancer pain on the quality of life. The presence of any maladaptive coping behaviors with cancer pain will interfere with the patient's life style and their quality of life, and will affect the nurse's role in caring, planning, and implementing effective nursing interventions to reduce and control cancer patient's pain. MATERIALS AND METHODS: A descriptive design was used for this study to assess the pain coping behavior Among Saudi patients suffering from advanced cancer. The study was conducted at the two tumor centers which deal with cancer patients in Jeddah City. A convenient sample of 132 patients with advanced cancer who were returning to the clinics, radiation therapy and medical oncology departments of the aforementioned tumor centers were included in the study. Data were collected by an interview schedule specially designed for this study, and the time ranged between 20-40 minutes. Tool's content validity and reliability were checked and established at 89% and 85%, respectively. Administrative approval from the two tumor centers in Jeddah City was obtained for study conduction. Different statistical methods were used for data analysis and interpretation to specify the value of correlation between study variables using SPSS v 10. RESULTS: Patients age were almost equally distributed among thirties (22%), forties (24.2%), fifties (20.5%), and sixties (22.7%). Females (59.1%) were slightly more than males (40.9%). About one half (47%) of them were diagnosed since one--two years age, and slightly more than half (56.8%) of them were unaware of their diagnosis. The major adaptive and Active pain coping behaviors included: religious practices such as: praying (99.2%); and listening or reciting the Holy Qur'an (98.5%). Cognitive methods such as: thinking that one is more stronger than the pain (99.2%); thinking that one is still in a satisfactory health despite the pain (98.5%); distracting oneself from pain (93.9%); visualization of pleasant scenes (92.4%); thinking about pleasant things (90.9%). The major maladaptive and passive pain coping behaviors included: decreasing activities by: specified positioning (97.7%); protecting the painful area (90.9%); and remaining still and avoiding movement (78%). Expression of feelings by: seeking help from others (90.2%); and crying or moaning (80.3%). Suppression of feelings and tolerating pain as it is (97%). CONCLUSIONS: Most of the adaptive and active pain coping behaviors were coming from patient's belief in god and their faith and trust and holding and obeying Islamic commands. The informational support by the health care professionals was unprovidable in the study sample, which brings the attention to the importance of nursing interventions in this area by providing coordinated and directed programs. PMID- 20590360 TI - Ethical dilemmas and the dying Muslim patient. AB - All health care providers may be confronted by a Muslim patient, but many health care professionals are lacking basic knowledge on the Muslim faith and medical ethics based on Islamic law (Shariah). One must endeavour to differentiate between ethnic customs and Islamic tradition. It is important for staff to have a general understanding of the principles of Islamic beliefs and actions to attain better cultural competency and improved patient care. Terminally ill cancer patients are vulnerable and require sensitive care of their physical, psycho social, cultural and spiritual aspects and needs. Muslims believe that the purpose of life is a test from God with the objective of full obedience, the outcome being purification of the soul and the resultant judgment after life to be directed to heaven or hell. The Muslim goal is to live and die in accordance with God's will, as revealed in the Qur'an and practiced by the Prophet. PMID- 20590361 TI - Psychiatric aspects of pain in cancer patients. AB - The goal of this review is to discuss the psychiatric aspects of pain in cancer patients from a biopsychosocial approach. Pain in cancer patients is considered as a complex reaction causing severe suffering and involves many psychological aspects. It has many dimensions such as personality, affect, cognition and social relations. The pain experience may also be influenced by some psychological factors such as anxiety, depression and the meaning of pain. Therefore, a successful management of cancer pain requires a multidisciplinary approach. Since cancer pain is generally treated medically, the psychological impact of pain is often underestimated. However, cancer pain is usually related to high levels of psychological distress. Culture, as an important factor affecting cancer pain, will also be discussed during this review. It is crucial to understand cultural diversity in the treatment of cancer patients with pain. Research shows that a minority patients of various ethnicities have less control of their pain because of the miscommunication problem within the medical setting. By paying attention to patients' cultural diversities, problems such as miscommunication causing inadequate control of pain can be eliminated. In order to manage pain in cancer patients, cognitive-behavioral interventions may be integrated with pharmacotherapy. The main goal of these strategies is to provide a sense of control and better coping skills to deal with cancer. Patients' maladaptive thoughts or behaviors may cause physical and emotional stress. Main behavioral strategies include biofeedback, relaxation training, and hypnosis. Cognitive strategies include guided imagery, distraction, thought monitoring and problem solving. By discussing all of these aspects of cancer pain, the multidimensional characteristic of pain and the relation between cancer pain and psychiatric factors will be clarified. PMID- 20590362 TI - The treatment gap of depression in persons with cancer. AB - The epidemiology of depression showed that the rates are high. For example, the World Mental Health Survey, an epidemiologic community study conducted in 28 countries, found a life-time prevalence rate that ranged from 3.3 % in Nigeria to 21.4% % in the US. With regard to persons with cancer, 12.5% of a sample of over 17,000 respondents over the age of 50 of a US survey of community-dwelling adults found that people that reported they had cancer had higher risk of fatigue (OR =1.5 95% CI 1.3-1.6); depression (OR=1.2, 95% CI 1.1-1.4) and pain (OR =1.2, 95% CI 1.03-1.3.).The rate of depression seems to be differently associated with cancer site. For example: It is higher in pancreatic cancer (33%-50%) and lung (11%-44%), and it is lower in lymphoma (8%-19%) and colon (13% and 25%). For breast cancer--likely the most studied cancer site- the prevalence ranges from 1.5% to 46%. Ciaramelli and Poli (2001) found that depressed persons had more pain and metastasis than the non-depressed but no more lifetime depression that the non-depressed. In terminally patients, studies have found that the higher the level of disability the higher the rates of depression. Interestingly, while almost all studies of depression in the community found higher rates in women than in men--this is far from the rule among persons with cancer. Despite the marked burden and the existence of effective treatment, a very large proportion of the persons with depression remain untreated. The causes to be imputed for the treatment gap are of different nature. Some of these causes are related to the suffering person, to the social context and to the health system. Often, the treating physicians fail to identify depression and to treat it properly. For example, in one evaluation of 456 outpatients with solid tumors a minority (14%) of the depressed were identified as such. Why is it important to assess depression in persons with cancer? Untreated depression both enhances the risks to life and it lowers the quality of life. It may be associated to a reduced chance of survival in women with early stage breast cancer. One possible reason is limited adherence to the treatment plan. Timely identification and well prescribed and conducted tre. PMID- 20590363 TI - Selected issues in palliative care among East Jerusalem Arab residents. AB - Understanding of cultural context is important when working with Palestinian patients, particularly in Israeli hospitals. Cultural competence includes individual assessment of communication needs and preferences. "This is God's will and one mustn't protest. A person who believes accepts all that God gives" (patient quote). PMID- 20590364 TI - PITPNM3 is an uncommon cause of cone and cone-rod dystrophies. AB - The first mutation in PITPNM3, a human homologue of the Drosophila retinal degeneration (rdgB not not) gene was reported in two large Swedish families with autosomal dominant cone dystrophy. To establish the global impact that PITPNM3 has on retinal degenerations we screened 163 patients from Denmark, Germany, the UK, and USA. Four sequence variants, two missence mutations and two intronic changes were identified in the screen. Thus, mutations in PITPNM3 do not appear to be a major cause of cone or cone-rod dystrophy. PMID- 20590366 TI - Array CGH as a potential predictor of radiocurability in intermediate risk prostate cancer. AB - Prostate cancer is the most common male cancer and up to one fifth of diagnosed patients will die of their disease. Current prognostic variables including T category (of the TNM staging), the absolute or kinetics of prostatic specific antigen (PSA) and the pathologic Gleason score (GS) are utilized to place men in low, intermediate and high-risk prostate cancer risk groupings. There is great heterogeneity within the non-indolent intermediate risk group with respect to clinical response. It is therefore imperative that further genetic and other prognostic factors be identified to better individualize treatment. Somatic alterations in prostate cancer. Herein, we review the potential for somatic alterations in tumor-associated genes (based on comparative genomic hybridization (CGH) in prostate cancers to be novel prognostic, and possibly predictive, factors for prostate cancer radiotherapy response. Intermediate risk prostate cancers show alterations in a number of genes thought to be involved in radiosensitivity, DNA repair, cell death and stem cell renewal. These include deletions at 21q (TMPRSS2: ERG), 13q (RB1), 10q (PTEN), 8p (NKX3.1), additions at 8q21 (containing c-Myc)) and haplo-insufficiency for p53, PARP1, ATM and DNA PKcs. Conclusions. The use of high-resolution CGH for fine-mapping of deletions and amplifications in pre-radiotherapy prostate cancer biopsies is feasible. Genetic alterations may delineate localized prostate cancer from systemic disease and be used as a predictive factor in that patients would be individually triaged to local (surgery versus radiotherapy) and/or adjuvant (adjuvant androgen ablation or post-operative radiotherapy) therapies in a prospective fashion to improve outcome. The knowledge of abnormal DNA repair pathways within in a given patient could allow for the judicious use of targeted agents (PARP/ATM inhibitors) as personalized medicine. PMID- 20590365 TI - Macromolecular and dendrimer-based magnetic resonance contrast agents. AB - Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed. PMID- 20590367 TI - Inter- and intrafractional localisation errors in cone-beam CT guided stereotactic radiation therapy of tumours in the liver and lung. AB - BACKGROUND: Localisation errors in cone-beam CT (CBCT) guided stereotactic body radiation therapy (SBRT) were evaluated and compared to positioning using the external coordinates of a stereotactic body frame (SBF) alone. Possible correlations to patient- or treatment-specific factors such as body mass index (BMI), planning time, treatment delivery time, and distance between tumour and spinal cord were explored to determine whether they influenced on the benefit of image-guidance. MATERIAL AND METHODS: A total of 34 patients received SBRT (3 fractions) for tumours in the liver (15 patients) or the lung (19 patients). Immobilisation and positioning was obtained with a SBF. Pre- and post-treatment CBCT scans were registered with the bony anatomy of the planning CT to find inter and intrafractional patient positioning errors (PPE). For lung tumour patients, matching was also performed on the tumours to find the tumour positioning errors (TPE) and baseline shifts relative to bony anatomy. RESULTS: The mean inter- and intrafractional 3D vector PPE was 4.5 +/- 2.7 mm (average +/- SD) and 1.5 +/- 0.6 mm, respectively, for the combined group of patients. For lung tumours, the interfractional misalignment was 5.6 +/- 1.8 mm. The baseline shift was 3.9 +/- 2.0 mm. Intrafractional TPE and baseline shifts were 2.1 +/- 0.7 mm and 1.9 +/- 0.6 mm, respectively. The magnitude of interfractional baseline shift was closely correlated with the distance between the tumour and the spinal cord. Intrafractional errors were independent of patient BMI, age or gender. CONCLUSION: Image-guidance reduced setup errors considerably. The study demonstrated the benefit of CBCT-guidance regardless of patient specific factors such as BMI, age or gender. Protection of the spinal cord was facilitated by the correlation between the tumour position relative to the spinal cord and the magnitude of baseline shift. PMID- 20590368 TI - Variants of milia successfully treated with CO(2) laser vaporization. AB - BACKGROUND: Milia are a usual consultation in dermatologic practice and optimal treatment modalities are not established. OBJECTIVE: To evaluate the efficacy and the safety of CO(2) laser vaporization in the treatment of milia. METHODS: We report four patients, aged from 12 to 50 years old, with different variants of milia: milia en plaque, milia post-photodermatitis, multiple eruptive milia and milia post-trauma. They were treated with the CO(2) laser in superpulsed and focused mode at 2 W/cm(2), with two passes in each session. The follow-up was 12 36 months. RESULTS: All patients showed marked improvement after a few sessions of CO(2) laser. No-one had recurrence or noticeable side effects. CONCLUSION: The CO(2) laser is an option in adult and child patients with multiple milia lesions or milia en plaque, obtaining good cosmetic results with minimal side effects. PMID- 20590369 TI - Controlled, randomized study evaluating the effects of treating cellulite with AWT/EPAT. AB - INTRODUCTION: Cellulite affects 95% of women and can lead to negative consequences. OBJECTIVE: To demonstrate the efficacy and safety of acoustic wave therapy (AWT) using extracorporeal pulse activation technology (EPAT) to manage cellulite. METHODS: Twenty-five women were included in the study and treated with AWT. Six AWT treatment sessions were performed over the course of 4 weeks. Three thousand pulses were applied to an area measuring approximately 10 x 15 cm on the thigh. The treatment was performed using the D-ACTOR 200 by STORZ MEDICAL AG (Tagerwilen, Switzerland). Follow-up visits were performed 1 week and 12 weeks after treatment. Changes in the skin structure were evaluated using the DermaTOP System (Eotech, Paris, France). Skin elasticity measurements were performed using the DermaLab Device (Cortex Technology, Hadsund, Denmark). RESULTS: The difference between treated and untreated legs was statistically significant with regard to depressions, elevations, roughness and elasticity after the first follow-up visit. CONCLUSION: The study showed that the AWT/EPAT treatment using the D-ACTOR 200 appears to be a safe and effective treatment alternative for the temporary improvement in the appearance of cellulite. PMID- 20590370 TI - Keratosis pilaris atrophicans: treatment with intense pulsed light in four patients. AB - BACKGROUND: Keratosis pilaris atrophicans (KPA) is a group of disorders characterized by erythematous keratotic papules followed by atrophy on the face. The treatment is often unsatisfactory. METHODS: Four white women, with ages ranging from 14 to 20 years, were treated with an intense pulsed light (IPL) system with a cut filter of 570 nm. The power density was between 40 and 47 J/cm(2), divided into two pulses of 3 ms, with a delay between both of 20 ms. Patients received five to nine sessions. RESULTS: Clinical improvement was noted in all patients, with a reduction of erythema in treated areas of between 75% and 100%. Treatment was well tolerated and no adverse reactions were observed. After a follow-up of 10 months no recurrence was observed. In addition, in parallel mode to erythema improvement, a reduction of roughness was observed. CONCLUSION: Our results suggest IPL should be considered as a safe treatment option in patients with KPA. PMID- 20590371 TI - Health professionals addressing alcohol use with pregnant women in Western Australia: barriers and strategies for communication. AB - Health professionals have an important role to play in preventing prenatal alcohol exposure. In 2006 qualitative data were collected from 53 health professionals working in primary care in metropolitan and regional Western Australia. Thematic analysis was used to elucidate barriers in addressing prenatal alcohol use and the strategies used to overcome them. Health professionals identified strategies for obtaining alcohol use information from pregnant women but they are not recognizing moderate alcohol intake in pregnant women. Study limitations are noted and the implications of the results are discussed. This research was funded by the Health Promotion Foundation of Western Australia. PMID- 20590372 TI - Validity of self-reported misuse of prescription opioid analgesics. AB - AIM: To determine concurrent validity of self-reported misuse of prescription opioids. DESIGN AND SETTING: Cross-sectional study in five U.S. methadone maintenance programs. PARTICIPANTS: 92 addicts. MEASUREMENTS: Self-reported questionnaire assessing past-month misuse of 14 opioid analgesics, and color photographs of five opioid analgesics with instructions to mark those used in the past month "to get high." Concordance between self-report and photograph endorsement was assessed via Kappa statistic. FINDINGS: 29 respondents completed both questionnaire and photograph endorsements. Kappas were 0.62 (OxyContin), 0.59 (methadone), 0.49 (Dilaudid), and 0.46 (generic extended-release oxycodone). CONCLUSIONS: Good-to-fair concurrent validity of self-reported abuse was seen for OxyContin, methadone, Dilaudid, and generic extended-release oxycodone. PMID- 20590373 TI - Cross-addiction on campus: more problems for student-athletes. AB - Data on 503 students from rural and urban areas were collected from January 2009 to October 2009 to test for cross-addiction of alcohol dependency with disordered gambling among college athletes and nonathletes. To test for alcohol dependency, the Michigan Alcohol Screening Test (MAST) was employed, while the South Oaks Gambling Screen (SOGS) was utilized to assess gambling behaviors. Athletes had higher frequencies of cross-addiction. For athletes there was a correlation between scores on the MAST and SOGS. Limitations related to data collection are discussed. Recommendations for further research directed toward the development of programs geared to assist students are given. PMID- 20590374 TI - The fast alcohol screening test (FAST) is as good as the AUDIT to screen alcohol use disorders. AB - This study was aimed at assessing the psychometric qualities of the fast alcohol screening test (FAST), and at comparing these qualities to those of the alcohol use disorders identification test (AUDIT) in three samples of Brazilian adults: (i) subjects attended at an emergency department (530); (ii) patients from a psychosocial care center (40); and (iii) university students (429). The structured clinical interview for diagnosis (SCID)-IV was used as gold standard. The FAST demonstrated high test-retest and interrater reliability coefficients, as well as high predictive and concurrent validity values. The results attest the validity and reliability of the Brazilian version of the FAST for the screening of indicators of alcohol abuse and dependence. PMID- 20590375 TI - The gateway hypothesis of substance abuse: an examination of its applicability in the Nigerian general population. AB - The study aims to estimate the prevalence and predictors of not following the gateway theory. Respondents were selected from a multistage stratified clustered sampling of households in five of Nigeria's six geopolitical regions. Interviews were conducted between February 2002 and May 2003 using the CIDI-version.3 with a total sample size (N) of 2,143. Cumulative incidence proportions of not following a gateway pattern were estimated with SUDAAN. Predictors of this were estimated using multivariate logistic regression models. The deviation from the normative sequence of drug use occurs albeit infrequently. The public health implications of this are discussed as well as the limitations of the findings. PMID- 20590376 TI - Parenting and maternal substance addiction: factors affecting utilization of child protective services. AB - The purpose of this study is to identify which personal, familial, environmental, and social factors are associated with the utilization of child protection services, including parental support programs, by mothers who misuse illicit substances. Participants are 56 mothers with substance use and addiction-related problems, of whom 32 were receiving, voluntarily or otherwise, child protection services while 24 mothers had psychotropic drug use-related problems but were receiving no psychosocial services. Data were collected in the province of Quebec, Canada, between August 1998 and August 1999 . Results indicate that mothers who receive services are younger, have fewer interpersonal resources, live in lower socioeconomic conditions, and have greater family dysfunction (less parental supervision and more inconsistent discipline) than mothers who do not receive services from child protection agencies. However, there are no significant differences between groups with regards to maternal childhood trauma, psychological distress, antisocial behavior and the quality of the parent-child bond. The results of this study suggest that although both groups misuse drugs and have personal difficulties, some mothers will not need support from social services to take care of their children. Implications of these findings for prevention are discussed. The study's limitations are noted. PMID- 20590377 TI - Why do adolescents drink? Motivational patterns related to alcohol consumption and alcohol-related problems. AB - The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed. PMID- 20590378 TI - Pregnancy under subutex (buprenorphine): opinions expressed on French internet forums. AB - Internet forums record the opinions and advice exchanged about pregnancy under Subutex. Two hundred and fourteen messages under 92 nicknames from four forums, especially dedicated to this subject in France, from August 2005 to July 2008 were collected and analyzed with QSR NIVIVO8. Most of the Internet users were women, pregnant, or with children, using Subutex. Very few professionals took part in them. The analysis of the opinions and representations of this substance, of medical practices, of exchanged advice, particularly on posology, was realized by the construction of a thematic tree. PMID- 20590379 TI - Nontobacco substance use, sexual abuse, HIV, and sexually transmitted infection among street children in Kolkata, India. AB - A community-based cross-sectional study among 554 Kolkata city street children assessed nontobacco substance use and sexual abuses along with human immunodeficiency virus (HIV)/ sexually transmitted infections (STIs) during 2007, using conventional cluster sampling technique for "hard-to-reach population" with a field-tested questionnaire and the collection of a blood sample for HIV and syphilis serology testing as a composite indicator of STIs. The reported prevalence of nontobacco substance use was 30%; 9% reported having been sexually abused. Some factors (age, lack of contact with family, orphan children, night stay at public place, etc.) were documented to be associated with substance use and sexual abuses. Seroprevalence of HIV was found to be 1% and that of STIs was 4%. This 1% HIV seroprevalence in street children is a matter of concern. Community-based intervention is necessary for them. The study's limitations are noted. PMID- 20590380 TI - Forbidden fruit and the prediction of cigarette smoking. AB - The concept of "forbidden fruit" has been popularly associated with adolescent cigarette smoking in the US. However, only a few empirical studies have been conducted to investigate how this construct operates among adolescents. We examined the concurrent and prospective relationships between two related concepts of forbidden fruit and adolescent cigarette smoking behavior and intention. We found some support for forbidden fruit attitudes as concurrent and longitudinal predictors of smoking and intention to smoke. Implications of these findings are discussed. PMID- 20590381 TI - Scalable platform for human embryonic stem cell differentiation to cardiomyocytes in suspended microcarrier cultures. AB - A scalable platform for human embryonic stem cell (hESC)-derived cardiomyocyte (CM) production can provide a readily available source of CMs for cell therapy, drug screening, and cardiotoxicity tests. We have designed and optimized a scalable platform using microcarrier cultures in serum-free media supplemented with SB203580 mitogen-activated protein kinase-inhibitor. Different microcarriers (DE-53, Cytodex-1 and 3, FACT, and TOSOH-10) were used to investigate the effects of type, size, shape, and microcarrier concentrations on the differentiation efficiency. hESCs propagated on TOSOH-10 (protamine derivatized 10-MUm beads) at the concentration of 0.125 mg/mL produced 80% beating aggregates, threefold cell expansion, and 20% of CMs (determined by fluorescence-activated cell sorting for myosin heavy chain and alpha-actinin expression). The ratio of CM/hESC seeded in this system was 0.62 compared to 0.22 in the embryoid body control cultures. The platform robustness has been tested with HES-3 and H1 cell lines, and its scalability was demonstrated in suspended spinner cultures. However, spinner culture yields dropped to 0.33 CM/hESC probably due to shear stress causing some cell death. Cells dissociated from differentiated aggregates showed positive staining for cardio-specific markers such as alpha-actinin, myosin heavy and light chain, troponin I, desmin, and emilin-2. Finally, CM functionality was also shown by QT-prolongation (QTempo) assay with/without Astemizole. This study represents a new scalable bioprocessing system for CM production using reagents that can comply with Good Manufacturing Practice. PMID- 20590382 TI - Good life good death according to Christiaan Barnard. AB - Christiaan Barnard (1922-2002), pioneering heart transplant surgeon, introduced his ideas on euthanasia in a well-written and researched book, Good Life Good Death. A Doctor's Case for Euthanasia and Suicide, published in 1980. His courage in analyzing this topic in a forthright and clear manner is worth reviewing today. In essence, Barnard supported and practiced passive euthanasia (the ending of life by indirect methods, such as stopping of life support) and discussed, but never practiced, active euthanasia (the ending of life by direct means). Barnard believed that "the primary goal of medicine was to alleviate suffering-not merely to prolong life-he argued that advances in modern medical technology demanded that we evaluate our view of death and the handling of terminal illness." Some in the surgical community took issue with Barnard when he publicized his personal views on euthanasia. We discuss Barnard's beliefs and attempt to clarify some misunderstandings regarding this particular controversial area of medicine. PMID- 20590383 TI - Surgical Research III. AB - In the "Importance of Medical and Surgical Research" (Surgical Research I), we introduced research as the key factor in the advancement of medicine and surgery. In Surgical Research II, we presented William Beaumont, Samuel Gross, and William Halsted as the main protagonists of the first wave of American surgical researchers during the 19th and early part of the 20th centuries. In this writing, i.e., Surgical Research III, we look ahead and include the following group of surgeon researchers: John B. Murphy; the Mayo Brothers, William J. Mayo and Charles H. Mayo; and George W. Crile. All of them contributed a great deal to the advancement of the medical science and the practice of surgery through research. All of them worked in different areas of surgery and contributed unique developments to the specialty. All of them demonstrated that questioning the way we practice could make surgery better and more secure. Surgical research buttressed the daily care of their surgical patients. PMID- 20590384 TI - Evaluation of the osteogenic performance of calcium phosphate-chitosan bone fillers. AB - There has been recent interest in utilizing calcium phosphates (CaPs) that set in situ for treating bone defects due to the limitations associated with morselized autografts and allografts. However, CaP cements have long setting times, poor mechanical properties, and poor osteoinductivity. This has prompted research toward finding a nonprotein-based compound, such as chitosan, to accelerate setting times and increase osteoinductivity. The purpose of this study was to compare bone growth rates during the early bone healing response achieved using conventionally prepared chitosan-CaP bone filler to an extensively purified chitosan-CaP compound. Both compounds set quickly and stimulated bone formation. Histomorphometry demonstrated a 290% increase in new bone formation when using the conventional chitosan-CaP bone filler and a 172% increase with the highly purified chitosan-CaP compound compared to the increase in bone formation seen with the unfilled control group. The results of this study indicate that a highly purified chitosan-CaP paste stimulated less bone formation than a conventionally prepared chitosan-CaP paste but both pastes have the potential to stimulate bone formation. PMID- 20590385 TI - Conversion of external fixation to definitive intramedullary nailing in experimental tibial fractures. AB - BACKGROUND AND PURPOSE: Initial treatment with external fixation of tibial fractures is indicated in severely injuried multitrauma patients. A conversion procedure to secondary nailing is often performed later to enhance fracture repair. The aim of the study was to compare definitive treatment of experimental tibial fractures with external fixation to an early conversion to secondary intramedullary nailing with large and small diameter nails. METHODS: Thirty male rats were subject to a standardized tibial shaft osteotomy initially stabilized with external fixation. On day 7, they were assigned to either the control group (group A, N = 10) or conversion to secondary nailing with a small (group B, N = 10) or large diameter nails (group C, N = 10). Evaluation at 60 days included radiography, dual energy radiographic absorptiometry (DXA), and mechanical bending testing. RESULTS: All fractures healed radiographically with bridging of the fracture line and more or less visible periosteal callus formation. Group B demonstrated significantly increased mineralization and callus formation measured as DXA parameters, bone mineral content (BMC), and callus area (CA) compared to both the other two groups. This group also tended to have mechanically stronger bones with higher fracture energy compared to both the other two groups, but no significant difference in mechanical prioperties between the groups was found in our study. INTERPRETATION: In conclusion, we found that conversion from external fixation of leg fractures in rats to intramedullary nailing did not improve bone healing significantly supporting external fixation as definitive fracture management. PMID- 20590386 TI - VEGF promotes angiogenesis and functional recovery in stroke rats. AB - We evaluated the effects of intranasal vascular endothelial growth factor VEGF on neurological function and angiogenesis in ischemic boundary following cerebral ischemia. Sprague-Dawley rats were randomized into sham operation group (n = 9), VEGF group (n = 18), and control group (n = 18). The VEGF and control rats were intranasally administered (IN) with VEGF or saline, starting three days after middle cerebral artery occlusion (MCAO) and daily. Neurological scores were obtained at 1, 7, and 14 days after MCAO. Rats were sacrificed at 14 days, the von Willebrand factor (vWF) immunoreactive, BrdU(+)/vWF(+) cells, and microvessels were evaluated respectively. Compared to the control rats, intranasal administration of VEGF improved behavioral recovery, and increased the number of vWF(+), BrdU(+)/vWF(+) cells, and FITC-dextran perfused microvessels in ischemic boundary (p < .01). Our data suggest that intranasal administration of VEGF may induce angiogenesis in ischemic boundary and improve behavioral recovery following cerebral ischemia in rats, which may provide a powerful strategy for stroke. PMID- 20590387 TI - Load measurement accuracy from sensate scaffolds with and without a cartilage surface. AB - ABSTRACT The use of "sensate" scaffolds covered with tissue-engineered cartilage has emerged as a possible treatment option for focal articular cartilage defects. The ability to monitor joint loading provides several benefits that can be useful in both clinical and research situations. Previous studies have shown that these scaffolds can accurately monitor in vivo joint loading during various activities. However, the effect that an articular cartilage layer or soft tissue overgrowth has on scaffold sensitivity has not been tested. Eight scaffolds were tested with cartilage samples taken from four hounds. Three strain gauges were attached to each scaffold and a servo hydraulics system was used to test sensitivity while the scaffold was in contact with cartilage, metal, or silicone surfaces. Strain gauge sensitivity was calculated from load and strain measurements collected during testing. There was no significant difference between the mean strain gauge sensitivities when the scaffolds were in contact with the different surfaces: cartilage 30.9 +/- 16.2 muepsilon/N, metal 31.8 +/- 18.6 muepsilon/N, and silicone 30.6 +/- 12.3 muepsilon/N. These results indicate that "sensate" scaffolds can be calibrated and used to monitor load with the presence of an articular cartilage layer. PMID- 20590388 TI - Prognostic significance of neuroepithelial transforming protein 1 in hepatocellular carcinoma. AB - OBJECTIVE: Recent works have demonstrated that neuroepithelial transforming protein 1 (NET-1) gene expression is associated with proliferation, metastasis, and clinical stages of human hepatocellular carcinoma (HCC). To investigate its prognostic significance in HCC, which currently is unknown, the authors examined the correlation between NET-1 expression and prognosis in patients with HCC. METHODS: Immunohistochemical staining was used to determine NET-1 expression level in 368 paired HCC and normal liver tissue (NLT) specimens. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of HCC. RESULTS: Among 368 specimens of HCC, the positive rate of NET-1 protein expression in HCC tissues was 86.7% (319/368), and the increased NET-1 expression was correlated significantly with high Edmondson-Steiner grade (p = .02) and TNM stage (p = .01). The expression level of NET-1 in HCC tissues was associated with intrahepatic metastasis (p = .008) and portal vein infiltration (p = .007). HCC patients with the moderate-strong NET-1 positive expression had either poorer disease-free survival or poorer overall survival than patients with negative-low positive NET-1 expression (p = .001 and .002, respectively). A multivariate Cox regression analysis revealed that NET-1 protein expression (relative risk 5.8; p = .01) was an independent prognostic factor for patients with HCC. CONCLUSION: Taken together, our study suggests for the first time that NET-1 status may be a new predictor of survival for HCC patients and provides the rationale for developing a novel therapy of targeting NET-1 against this fatal malignancy. PMID- 20590389 TI - Ferguson hemorrhoidectomy with radiofrequency versus classic diathermy. AB - BACKGROUND: This randomized study compared results obtained with the Ferguson's technique for the treatment of hemorrhoids performed with a radiofrequency (RF) scalpel and traditional diathermy. METHODS: 28 patients affected by grade IV hemorrhoids were randomized to receive either the Ferguson operation with the RF scalpel (group A) or traditional diathermy (group B). The operating time, intra- and postoperative bleeding, postoperative pain, and overall patient satisfaction were all recorded. RESULTS: Six patients (three for each group) did not attend follow-up controls. Group A showed a significant reduction of the surgical time (23 vs. 33 min; p < .01), pain at first postoperative day (Visual Analog Scale [VAS] score 3.4 vs. 4.8; p < .05), and at the first evacuation (3.4 vs. 5.0; p < .05). No significant differences were observed for the pain score at the seventh postoperative day, or overall satisfaction scores at the 7th postoperative day, and six months postoperatively (p = NS). No severe complications were recorded. Two patients in group A (18.2%) and four patients in group B (36.4%) reported transitory gas incontinence that spontaneously resolved within one month (p = NS). Three patients in group A (27.3%) and four patients in group B (36.4%) required postoperative catheterization due to urinary retention (p = NS). CONCLUSIONS: RF scalpel shortens the operating time of the Ferguson operation and is less painful in the early postoperative period. PMID- 20590390 TI - Topical Ankaferd application to presacral bleeding due to total mesorectal excision in rectal carcinoma. PMID- 20590391 TI - Statement of humane animal care. PMID- 20590393 TI - Dietary supplementation: effects on visual performance and occurrence of AMD and cataracts. AB - OBJECTIVE: To evaluate results of studies that have provided information regarding the effects of dietary supplementation on visual performance, development and progression of age-related macular degeneration (AMD), and risk for cataracts. RESEARCH DESIGN AND METHODS: Studies with information about the effects of dietary supplementation were identified via PubMed searches that combined (in separate searches) the terms 'supplement' OR 'supplementation' OR 'diet' AND 'cataract' or 'macular degeneration' or 'visual' OR 'vision'. Additional references concerned with biologic effects of specific agents, measurement of visual function, and the etiology and epidemiology of cataracts and AMD were identified on the basis of PubMed conventional literature searches. RESULTS: Studies of the effects of dietary supplementation, primarily with preparations including lutein and zeaxanthin, have demonstrated improvements in contrast sensitivity and visual performance under glare conditions that, in some studies, have been correlated with effects of treatment on macular pigment optical density. Results from both observational and prospective interventional studies generally support the conclusion that dietary supplements including these xanthophylls significantly decrease the occurrence of AMD and the development of nuclear lens opacities. However, there is variability in results regarding effects of dietary supplementation that may be related to limitations of long term observational or interventional studies and which cannot be easily controlled or which may also be related in some studies to other important, yet unrecorded, diet- and lifestyle-related factors that are capable of influencing the risks for AMD and/or cataracts. CONCLUSIONS: The multiple benefits of dietary supplementation support the development and use of these preparations to promote optimal visual function and decrease risk for AMD and cataracts. Increasing understanding of the optimal approach to supplementation will depend upon results from interventional studies that also carefully evaluate and analyze well established factors for these two conditions. PMID- 20590394 TI - Phacoemulsification-deep sclerectomy modified by trabeculum microperforations and implantation of lens anterior capsule as autologous scleral implant. AB - OBJECTIVE: To evaluate the efficacy and safety of Phacoemulsification-deep sclerectomy modified by trabeculum microperforations and anterior lens capsule as autologous scleral implant (mPDS) for open-angle glaucoma. RESEARCH DESIGN AND METHOD: A case series study comprised 127 patients and 127 eyes after mPDS. The applied modification of deep sclerectomy consisted in creating microperforations within the posterior trabeculum and in fixing the anterior lens capsule, removed during phacoemulsification, in the scleral lake as an autologous intrascleral implant. Primary open-angle glaucoma without satisfying intraocular pressure (IOP) control (>or=21 mmHg) despite maximally tolerated medications or with progression of visual field and cataract was the indication for surgery. For statistical analyses paired Student's t-test, the Wilcoxon signed rank test and one-dimensional ANOVA with repeated measures were used; survival analysis was performed using the Kaplan-Meier method. MAIN OUTCOME MEASURES: IOP, number of medications and best corrected visual acuity (BCVA) were examined. On the basis of the assessment of the anterior and posterior segments of the eye, the character and also the degree of intensification of postoperative complications were established. Follow-up examinations were performed on days 1 and 7, and at 1, 3, 6, 12, 18 and 24 months and thereafter every 6 months. The complete success rate was defined as IOP 21 repeats for the 90(CA)(14-24) were more common in blacks than in whites (61.9% in blacks and 49.3% in whites; p=0.0017). We found no interethnic differences for the Q279R polymorphism. Moreover, two haplotypes that combine "detrimental" alleles were found at higher frequencies in blacks than in whites (31% vs. 16.4%, respectively; p<0.05). The interethnic differences being reported here replicate those previously found with smaller number of subjects in the Hapmap or Seattle SNPs data and may help explain the higher prevalence of cancer and cardiovascular diseases in blacks compared with whites. Our findings suggest a proportional significance of these polymorphisms in each ethnic group. PMID- 20590474 TI - Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. AB - DNA repair gene alterations may cause a reduction in DNA repair capacity and influence an individual's susceptibility to carcinogenesis. We hypothesized that single nucleotide polymorphisms of DNA repair genes may be a risk factor for prostate cancer (PCa) susceptibility, influencing expression of homologous recombination (XRCC3) and nonhomologous end-joining (XRCC7) genes and conferring predisposition to PCa. In a case-control study, genotyping was done in 192 patients with PCa and 224 age matched unrelated healthy controls of similar ethnicity to determine variants in XRCC3 Exon 7 (C18067T, rs861539), IVS5-14 (A17893G, rs1799796), and XRCC7 Intron 8 (G6721T, rs7003908) by polymerase chain reaction-restriction fragment-length polymorphism methods. Variant genotype GG (odds ratio [OR], 2.23; p=0.003) and combined genotype TG+GG (OR, 1.541; p=0.049), G allele of XRCC7 Intron 8 (G>T), demonstrated significant risk for PCa (OR, 1.529; p=0.002). Stratification on bases of Gleason grade and bone metastasis, significant risk with high Gleason grade for CT genotype of XRCC3 Exon 7, and variant genotype GG of XRCC7 Intron 8 were observed. Our results strongly support that common sequence variants (GG) genotype of XRCC7 may increase risk of PCa. G allele being a risk allele in our study also suggests that this polymorphism be used as a marker for the PCa susceptibility. PMID- 20590475 TI - Spectroscopic studies on the interaction of isatin with calf thymus DNA. AB - The interaction of native calf thymus DNA (CT-DNA) with isatin was studied at physiological pH by spectrophotometric, spectrofluorometric, competition experiment, circular dichroism, and viscometric techniques. No red shift and isobestic points are observed in UV absorption band of isatin. A strong fluorescence quenching reaction of DNA to isatin was observed, and the binding constants (Kf) of DNA with isatin and corresponding numbers of binding sites (n) were calculated at different temperatures. Thermodynamic parameters enthalpy change (DeltaH) and entropy change (DeltaS) were calculated to be +27.42 kJ mol-1 and +201 J mol-1 K-1 according to Van't Hoff's equation, which indicated that the reaction is predominantly entropically driven. DNA viscosity and iodide quenching results suggest that isatin does not intercalate into the DNA base pairs. Circular dichroism spectra of CT-DNA indicated deep conformational changes in the DNA double helix. These results indicate that isatin interacts with CT-DNA via groove binding mode. PMID- 20590476 TI - ABM Clinical Protocol #7: Model Breastfeeding Policy (Revision 2010). AB - A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID- 20590477 TI - A pharmacological and phytochemical evaluation of medicinal plants used by the Harbang clan of the Tripura tribal community of Mirsharai area, Chittagong district, Bangladesh. AB - BACKGROUND: Recent years have witnessed a continual decline of medicinal plant availability as well as a decline in the numbers of tribal traditional healers and their medicinal knowledge in Bangladesh. Yet these medicinal plants used for treatment of various ailments by tribal traditional healers can be of considerable interest to modern science in their potential for discovery of lead compounds, which can lead to better drugs. OBJECTIVE: The primary objective of the present study was to conduct an ethnomedicinal survey among the traditional healers of the Harbang clan (Tripura tribe) of Mirsharai to gain information on medicinal plants used to treat various ailments with the further objective of evaluating the efficacy of these medicinal plants when compared with known phytochemicals and modern-research-based pharmacologic activity studies on these plants. METHODS: Semistructured interviews and guided field-walk methods were used to gather information on medicinal plants used by the Tripura traditional healers. Along with plants, information was also collected on plant parts used, formulations, and dosages. Information on phytochemicals as well as pharmacologic activity studies on these plants (if any) was obtained from several data bases. SETTING: The survey was conducted among the traditional healers of the Harbang clan (Tripura tribe) residing in Mirsharai, Chittagong district, Bangladesh. RESULTS: The traditional healers of the Tripura tribal community of Mirsharai use 64 plant species distributed into 38 families for treatment of various ailments. CONCLUSIONS: Information on phytochemicals and pharmacologic activity studies conducted on a number of the plants (used by Tripura tribal healers) by modern scientific methods validated the traditional use of a number of plants and suggested that they can form a good source of newer drugs. The survey further highlighted the importance of gathering such ethnomedicinal information for effective conservation of tribal medicinal knowledge and medicinally important plant species. PMID- 20590479 TI - Efficacy of a whole-body vibration intervention on functional performance of community-dwelling older adults. AB - OBJECTIVE: The objective of this study was to investigate efficacy of a whole body vibration (WBV) intervention on functional performance of community-dwelling older adults. DESIGN: The study was designed as a randomized controlled trial. SETTING: The setting was in community centers. SUBJECTS: There were 37 total subjects (21 women and 16 men) (age 69 +/- 8 years; mean +/- standard deviation). INTERVENTION: Participants were randomized to a WBV intervention (INT) group and control (CON) group. Whole-body vibration was administered for five 1-minute bouts per session, 3 days per week, for 6 weeks. The CON group was asked not to commence any form of physical training. OUTCOME MEASURES: Functional performance was measured with the timed-up-and-go-test (TUG) and sit-to-stand-test (STS). RESULTS: After WBV, TUG and STS time was less for INT than CON (INT, TUG 7.6 +/- 0.3 seconds, STS 11.9 +/- 2.0 seconds; CON, TUG 8.6 +/- 0.9, STS 13.5 +/- 1.1 seconds; p < 0.05). Within INT, TUG improved 0.9 +/- 0.4 seconds; p = 0.01 and STS improved 3.0 +/- 0.9 seconds; p = 0.05). CONCLUSIONS: The efficacy of this WBV intervention was established. Functional performance improvement after WBV may be attributed to a number of biological mechanisms that remain speculative. Further research is required to mechanistically understand the effects of WBV on older adults. PMID- 20590478 TI - A randomized clinical trial of St. John's wort for smoking cessation. AB - INTRODUCTION: St. John's wort (SJW) is a widely used herbal supplement. The predominant mechanism(s) accounting for the activity of SJW in vivo are, however, unclear. The purpose of this study was to investigate the efficacy of SJW for smoking cessation. METHODS: We conducted a randomized, blinded, placebo controlled, three-arm, dose-ranging clinical trial. A total of 118 subjects were randomly allocated to receive SJW 300 mg, 600 mg, or a matching placebo tablet 3 times a day combined with a behavioral intervention for 12 weeks. Self-reported smoking abstinence was biochemically confirmed with expired air carbon monoxide. RESULTS: Mean age of the study participants was 37.6 +/- 12.4 years; they smoked an average of 20.0 +/- 6.6 cigarettes per day for 20 +/- 12.1 years. The study dropout rate was high (43%). By intention-to-treat analysis, no significant differences were observed in abstinence rates at 12 and 24 weeks between SJW dose groups and placebo. SJW did not attenuate withdrawal symptoms among abstinent subjects. Abstinence rates did not differ by study group among subjects who took at least 75% of their study medication. No significant side-effects were noted with SJW. CONCLUSIONS: In this randomized trial, SJW did not increase smoking abstinence rates. Our data, in combination with data from other studies, suggest that SJW has little role in the treatment of tobacco dependence. PMID- 20590480 TI - Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. AB - OBJECTIVE: The objective of this study was to investigate the effectiveness of Bacopa monnieri Linn. for improvement of memory performance in healthy older persons. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: The trial took place in Lismore, NSW, Australia between February and July 2005. Ninety-eight (98) healthy participants over 55 years of age were recruited from the general population. INTERVENTIONS: Participants were randomized to receive an extract of Bacopa monnieri called BacoMind(TM) (Natural Remedies Pvt. Ltd.), 300 mg/day, or an identical placebo. Following screening, neuropsychologic and subjective memory assessments were performed at baseline and at 12 weeks. OUTCOME MEASURES: Audioverbal and visual memory performance were measured by the Rey Auditory Verbal Learning Test (AVLT), the Rey-Osterrieth Complex Figure Test (CFT), and the Reitan Trail Making Test (TMT). Subjective memory performance was measured by the Memory Complaint Questionnaire (MAC-Q). RESULTS: One hundred and thirty-six (136) subjects volunteered; 103 met entry criteria, 98 commenced, and 81 completed the trial. Bacopa significantly improved verbal learning, memory acquisition, and delayed recall as measured by the AVLT: trial a4 (p = 0.000), trial a5 (p = 0.016); trial a6 (p = 0.000); trial a7 (delayed recall) (p = 0.001); total learning (p = 0.011); and retroactive interference (p = 0.048). CFT, MAC-Q, and TMT scores improved but group differences were not significant. Bacopa versus placebo caused gastrointestinal tract (GIT) side-effects. CONCLUSIONS: Bacopa significantly improved memory acquisition and retention in healthy older Australians. This concurs with previous findings and traditional use. Bacopa caused GIT side effects of increased stool frequency, abdominal cramps, and nausea. PMID- 20590481 TI - Therapeutic massage of the neck and shoulders produces changes in peripheral blood flow when assessed with dynamic infrared thermography. AB - OBJECTIVE: This study's objective was to determine the effect of therapeutic massage on peripheral blood flow utilizing dynamic infrared thermography in a constant temperature/humidity thermal chamber to assess noncontact skin temperature. DESIGN: The design was a repeated-measures crossover experimental design; the independent variable was treatment condition (massage, light touch, control). SETTING: The study setting was a university research laboratory. SUBJECTS: Seventeen (17) healthy volunteers (8 males/9 females; age = 23.29 +/- 3.06) took part in the study. INTERVENTIONS: One (1) 20-minute neck and shoulder therapeutic massage treatment was performed for each of the three treatment conditions. OUTCOME MEASURES: The dependent variable was noncontact, mean skin temperature in 15 regions measured at 6 time points (pretest and 15, 25, 35, 45, and 60 minutes post-test) for each treatment condition. RESULTS: The massage treatment produced significant elevations in temperature in five regions: anterior upper chest (p = 0.04), posterior neck (p = 0.0006), upper back (p = 0.0005), posterior right arm (p = 0.03), and middle back (p = 0.02). Massage therapy produced significant increases in temperature over time, compared to the other conditions, in the anterior upper chest, and posterior neck, upper back, right arm, and the middle back. Additionally, the temperatures remained above baseline levels after 60 minutes. Interestingly, the massage treatment produced significant temperature elevations in two nonmassaged areas posterior right arm and middle back. CONCLUSIONS: These changes in temperature suggest corresponding changes in peripheral blood flow in the treated areas as well as in adjacent not massaged areas. Moreover, the results suggest dynamic infrared thermography as a useful tool to measure noninvasive, noncontact changes in peripheral blood flow for massage therapy research. PMID- 20590482 TI - Effects of complementary therapy on health in a national U.S. sample of older adults. AB - OBJECTIVES: The study objectives were to identify types of complementary therapy that are most predictive of health outcomes, including functional status, physical health-related quality of life (HRQoL), and mental HRQoL among older adults. DESIGN: This was a prospective study. SETTINGS/LOCATION: The study comprised computer-assisted interviews conducted in participants' homes. SUBJECTS: Subjects included 1683 adults aged 55 and older who participated in the 2002 National Health Interview Survey and the 2003 Medical Expenditure Panel Survey. INTERVENTION: None. OUTCOME MEASURES: Functional status, physical HRQoL, and mental HRQoL at 1-year follow-up. RESULTS: The use of biologically based therapies predicted better functional status, such that users reported less functional impairment than nonusers (p < 0.01), adjusting for age, gender, race/ethnicity, education, health insurance, household income, and comorbid conditions. Users of manipulative and body-based methods reported less functional impairment (p < 0.05). They also reported better physical and mental health related quality of life, though these relationships were marginally significant. Other groups of therapies, alternative medical systems, mind-body therapies, and prayer were not predictive of either functional status or HRQoL. CONCLUSIONS: Favorable effects were observed among users of biologically based therapies and users of manipulative and body-based methods. Other types of complementary therapy had no effects on health status over a 1-year follow-up period. PMID- 20590483 TI - Chinese medicine students' preparedness for clinical practice: an Australian survey. AB - BACKGROUND: Little is known about how prepared Chinese medicine (CM) students perceive themselves to enter the workforce. OBJECTIVE: The objective of this study was to investigate perceptions of preparedness for clinical practice of final-year CM students in Australia. DESIGN: The study design consisted of a written survey focusing on eight dimensions relating to practice: Interpersonal Skills, Confidence/Coping Skills, Professional Networks, Professional Practice Management, Professional Patient Management, Prevention, Holistic Care, and Self Directed Learning. Part 1 of the survey required participants to choose from six possible responses on how well they believe their CM course has prepared them in relation to 41 statements about aspects of practice (1 = very inadequately through to 6 = very adequately). Part 2 consisted of nine open-ended questions. STUDY PARTICIPANTS: The study participants were final-year Bachelor degree CM and acupuncture students from Australian universities and privately operated educational institutions. ANALYSIS AND MAIN OUTCOME MEASURES: Part 1 of survey: mean scores on the eight dimensions of practice. Part 2 of survey: transcribed responses were imported into NVivo8. Each part of the questions was analyzed and grouped into broad themes. RESULTS: Seventy-one (71) of one hundred and seven (71/107) invited students (average age 29.4 years +/- 7.4 years) participated in the survey conducted in 2008. Mean scores on eight dimensions of clinical practice were as follows: Interpersonal Skills 3.9 (+/-1.1), Confidence/Coping Skills 4.0 (+/-0.8), Professional Networks 4.2 (+/-0.8), Professional Practice Management 4.2 (+/-0.8), Professional Patient Management 4.7 (+/-0.7), Prevention 4.6 (+/-0.7), Holistic Care 4.4 (+/-0.7), and Self-Directed Learning 4.6 (+/ 0.6). There was no significant difference in mean scores across gender. Responses to Part 2 indicated a range of suggestions on the strengths of educational courses and how transition to clinical practice could be facilitated. CONCLUSIONS: In general, CM students perceived themselves to be "somewhat adequately" or "adequately" prepared for various aspects of clinical practice. Survey results may help inform CM educators about how to better prepare students for entry into the workforce. PMID- 20590484 TI - Outcomes of comprehensive heart care programs in high-risk women. AB - OBJECTIVE: The purpose of this study was to improve the fund of knowledge, reduce cardiovascular disease (CVD) risk, and attain Healthy People 2010 objectives among women in model women's heart programs. METHODS: A 6-month pre/post longitudinal educational intervention of high-risk women (n = 1310) patients at six U.S. women's heart programs consisted of comprehensive heart health counseling and use of American Heart Association/American College of Cardiology (AHA/ACC) Evidence-Based Guidelines as enhancement to usual care delivered via five integrated components: education/awareness, screening/risk assessment, diagnostic testing/treatment, lifestyle modification/rehabilitation, and tracking/evaluation. Demographics, before and after knowledge surveys, clinical diagnoses, laboratory parameters, and Framingham risk scores were also determined. Changes in fund of knowledge, awareness, and risk reduction outcomes and Healthy People 2010 objectives were determined. RESULTS: At 6 months, there were statistically significant improvements in fund of knowledge, risk awareness, and clinical outcomes. Participants attained or exceeded >90% of the Healthy People 2010 objectives. Proportions of participants showing increased knowledge and awareness of CVD as the leading killer of women, of all signs and symptoms of a heart attack, and calling 911 increased significantly (11.1%, 25.4%, and 34.6%, respectively). Health behavior counseling for physical activity, diet, and diabetes as CVD risk factors increased significantly (28.3%, 28.2%, and 12.5%, respectively). There was a statistical 4.1% increase in participants with systolic blood pressure (SBP) <140/90 mm Hg, a 4.7% decrease in participants with total cholesterol (TC) >240 mg/dL, a 4.5% decrease in participants with TC >200 mg/dL, a 5.9% decrease in participants with high-density lipoprotein cholesterol (HDL-C) <50 mg/dL, a 4.4% decrease in participants with HDL-C <40 mg/dL, and an 8.8% increase in diabetics with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. CONCLUSIONS: CVD prevention built around a comprehensive heart care model program and AHA/ACC Evidence-Based Guidelines can be successful in improving knowledge and awareness, CVD risk factor reduction, and attainment of Healthy People 2010 objectives in high-risk women. Thus, these programs could have a dramatic and lasting impact on the health of women. PMID- 20590485 TI - Improving blood pressure control rates by optimizing combination antihypertensive therapy. AB - IMPORTANCE OF THE FIELD: Hypertension is the most common preventable cause of cardiovascular morbidity and mortality. Despite the availability of a multitude of antihypertensive drugs, blood pressure (BP) control rates remain poor in the majority of patients with hypertension due to both patient- and clinician-related factors. The purpose of this review is to describe how healthcare professionals can best utilize combination therapy to optimize patient antihypertensive treatment and achieve BP goals. AREAS COVERED IN THIS REVIEW: Data are discussed describing the common need for multiple antihypertensive agents for achieving BP control, importance of the time required for BP control on patient outcomes, and key clinical trial experiences for guiding decisions in antihypertensive regimen selection, with particular attention to the efficacy and tolerability of triple therapy combinations and the benefits and disadvantages of single-pill formulations for combination regimens. Literature searches of these various topics were conducted in July 2009 (using no time period limits), with the paper later updated with published literature available as of May 2010 (including abstracts from the 2010 annual meeting of the American Society of Hypertension). WHAT THE READER WILL GAIN: The reader will derive an appreciation for general need for the use of two, and often three or more, antihypertensive agents for achieving BP goals, supporting the importance of thorough patient assessment in determining the appropriateness of combination therapy early in the course of treatment. They will also be updated as to the clinical trial data available for triple-therapy combinations, including both published and recently presented data. TAKE HOME MESSAGE: By optimizing efficacy, decreasing side effects, and increasing adherence, combination therapy using single-pill combinations can improve outcomes in patients with mild to moderate hypertension. PMID- 20590488 TI - Questions cause of spinal cord compression in dog. PMID- 20590489 TI - What is your diagnosis? Bone fragment in hock joint. PMID- 20590490 TI - What is your diagnosis? Chondroid chondrosarcoma. PMID- 20590491 TI - What is your neurologic diagnosis? Intranasal osteosarcoma. PMID- 20590492 TI - Diagnostic imaging in veterinary dental practice. Dental caries. PMID- 20590493 TI - Pathology in practice. Osteochondroma. PMID- 20590494 TI - What is the evidence? Intervertebral disk surgery. PMID- 20590495 TI - Faculty perspectives regarding the importance and place of nontechnical competencies in veterinary medical education at five North American colleges of veterinary medicine. AB - OBJECTIVE: To explore perceptions of faculty educators regarding the importance of nontechnical competencies in veterinary graduates and the placement of nontechnical competency development in veterinary education. DESIGN: Survey. SAMPLE POPULATION: All faculty members at 5 North American veterinary medical institutions. PROCEDURES: Participants rated the importance of 14 nontechnical competencies and indicated in which phase or phases of veterinary education such competencies should be developed (ie, curriculum placement). Differences in mean ratings were statistically evaluated, as were associations between ratings or curriculum placement and respondent institution, gender, experience, and discipline. RESULTS: Mean ratings of importance were above neutral for all competencies and were highest for ethical, critical thinking, and interpersonal and intrapersonal competencies; development of these competencies was favored in preveterinary and veterinary training. Ratings were lower for management and business competencies; development of these and other competencies was placed primarily in the clinical phase of the veterinary curriculum. Basic science, nonveterinarian, and junior faculty appeared to more strongly appreciate the importance of nontechnical skills, whereas large animal and midcareer faculty reported a more reserved degree of support. Female faculty were more likely to place nontechnical competency development throughout the educational process. CONCLUSIONS AND CLINICAL RELEVANCE: Participants agreed nontechnical competencies are important for veterinary graduates; however, faculty perceptions differed from previously published findings regarding the relative importance of business and management skills. Those involved in faculty hiring, faculty development, and curricular planning should also be aware of disciplinary and career stage differences affecting faculty perspectives. PMID- 20590496 TI - Use of an activity monitor to detect response to treatment in dogs with osteoarthritis. AB - OBJECTIVE: To determine whether an activity monitor (AM) could be used to detect changes in activity in dogs with osteoarthritis treated with carprofen or a placebo. DESIGN: Randomized controlled trial. ANIMALS: 70 dogs with no clinically important abnormalities other than osteoarthritis for which they were not currently being treated. PROCEDURES: Dogs wore an AM continuously for 21 days. On days 8 through 21, the dogs were treated with carprofen (n = 35) or a placebo (35). Total activity counts for days 1 through 7 (baseline) were compared with total activity counts for days 15 through 21 (endpoint). The change in total activity count from baseline to endpoint was assessed within each treatment group as well as between groups. Linear regression analysis was performed to test for an association between treatment and percentage change in activity counts while controlling for other variables. RESULTS: For placebo-treated dogs, median baseline total activity count was not significantly different from median endpoint total activity count (1,378,408 vs 1,310,112, respectively). For dogs receiving carprofen, there was a significant increase in median activity count from baseline to endpoint (1,276,427 vs 1,374,133). When age and baseline activity counts were controlled for, dogs in the carpofen-treated group had a 20% increase in activity counts, compared with placebo-treated dogs (95% confidence interval, 10% to 26%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that the AM used in the present study may be a valid outcome assessment tool for documenting improved activity associated with treatment in dogs with osteoarthritis. PMID- 20590497 TI - Serologic prevalence of antibodies against canine influenza virus (H3N8) in dogs in a metropolitan animal shelter. AB - OBJECTIVE: To determine the prevalence of exposure to canine influenza virus (CIV) in dogs in a metropolitan animal shelter. DESIGN: Serologic survey. ANIMALS: 74 dogs. PROCEDURES: Dogs were randomly selected from the canine shelter population. A physical examination was performed, and blood samples were obtained and submitted for serologic testing for the detection of antibodies against CIV. Logistic regression analysis was performed to evaluate the association of factors (body condition score, nasal discharge, coughing, rectal temperature, number of days in the shelter, and relinquished vs stray) with positive results. RESULTS: 31 of 74 (42%) dogs were seropositive for antibodies against CIV. Positive serologic test results were detected for 6 of 39 (15%) dogs housed in the shelter for 8 days. Number of days in the shelter was the only factor significantly associated with positive serologic test results. For every 3 days in the shelter, the odds of a positive serologic test result increased significantly by 2.2 (95% confidence interval, 1.5 to 3.4). CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results suggested that more dogs were exposed to CIV in the shelter than were exposed in the urban environment. This has serious implications for design and management of animal shelters. PMID- 20590498 TI - Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. AB - OBJECTIVE: To determine the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and to describe treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. DESIGN: Cross-sectional study. SAMPLE POPULATION: 38 isolates classified as resistant to macrolide antimicrobials or rifampin received from 9 veterinary diagnostic laboratories between January 1997 and December 2008. PROCEDURES: For each isolate, the minimum inhibitory concentration of macrolide antimicrobials (ie, azithromycin, erythromycin, and clarithromycin) and rifampin was determined by use of a concentration-gradient test. Prevalence of R equi isolates from Florida and Texas resistant to macrolide antimicrobials or rifampin was determined. Outcome of antimicrobial treatment in foals infected with antimicrobial-resistant isolates of R equi was determined. RESULTS: Only 24 of 38 (63.2%) isolates were resistant to >or= 1 antimicrobial. Two isolates were resistant only to rifampin, whereas 22 isolates were resistant to azithromycin, erythromycin, clarithromycin, and rifampin. The overall prevalence of antimicrobial-resistant isolates in submissions received from Florida and Texas was 3.7% (12/328). The survival proportion of foals infected with resistant R equi isolates (2/8 [25.0%]) was significantly less, compared with the survival proportion in foals that received the same antimicrobial treatment from which antimicrobial-susceptible isolates were cultured (55/79 [69.6%]). Odds of nonsurvival for foals infected with resistant R equi isolates were 6.9 (95% confidence interval, 1.3 to 37) times the odds for foals infected with susceptible isolates. CONCLUSIONS AND CLINICAL RELEVANCE: Interpretation of the results emphasized the importance of microbiological culture and antimicrobial susceptibility testing in foals with pneumonia caused by R equi. PMID- 20590499 TI - Use of a modified Vinsot technique for partial phallectomy in 11 standing horses. AB - CASE DESCRIPTION: 6 geldings and 5 stallions were evaluated from January 2007 through April 2009 for the following conditions requiring phallectomy: chronic paraphimosis (n = 7), squamous cell carcinoma of the penis (3), and priapism (1). CLINICAL FINDINGS: None of the 7 horses with paraphimosis was able to retract the penis. Chronicity of the paraphimosis in 6 horses ranged from 2 weeks to 2 months and was unknown in the seventh horse. Horses with paraphimosis had been medically treated without success. The horse with priapism had developed the condition secondary to acepromazine administration 2 days prior to referral and was unsuccessfully treated once by intracavernosal administration of phenylephrine and irrigation of the cavernosal tissues prior to surgery. The 3 horses with squamous cell carcinoma of the penis had had the condition for 2 years and had been treated by repeated application of a cryogen or chemotherapeutic agent to the lesions. TREATMENT AND OUTCOME: All 11 horses underwent a partial phallectomy by means of a modified Vinsot technique. Modifications to the original technique included creation of a linear urethrostomy, alteration of the location and shape of the urethrostomy, application of a latex tourniquet, concurrent castration of stallions, and use of the procedure in standing horses. The procedure was technically easy to perform, well tolerated by the horses, and cosmetically acceptable to the owners, and had minimal postoperative complications. Long-term follow-up information was obtained from owners of 10 horses a median of 454 days after surgery; 2 owners reported mild urine scalding as the only adverse effect. CONCLUSIONS AND CLINICAL RELEVANCE: The modified Vinsot technique of partial phallectomy was effective and may be useful for horses that are unsuitable candidates for general anesthesia because of medical or owner financial constraints. PMID- 20590500 TI - Outbreak of malignant catarrhal fever among cattle associated with a state livestock exhibition. AB - CASE DESCRIPTION: Severe disease and death were identified in cattle exhibited at a state fair that were naturally infected with ovine herpesvirus type 2 (OvHV-2). CLINICAL FINDINGS: Most affected cattle had anorexia, signs of depression, diarrhea, fever, and respiratory distress ultimately leading to death. Mean duration of clinical signs prior to death was 6 days (range, 1 to 26 days). Mean number of days between apparent exposure and death was 71 days (range, 46 to 139 days). TREATMENT AND OUTCOMES: 19 of 132 cattle cohoused in 1 barn died of malignant catarrhal fever (MCF). The diagnosis of sheep-associated MCF was confirmed on the basis of results of an OvHV-2-specific PCR assay performed on tissue samples obtained from affected cattle. The disease was associated but not significantly with distance from the center of the barn and was not associated with distance from the center of the sheep pens. CLINICAL RELEVANCE: Outbreaks of MCF in cattle are unusual, particularly in association with livestock exhibitions. Because the clinical signs may be similar to those of some transboundary diseases, cases of MCF should be reported and investigated. Findings for this outbreak provided evidence to suggest that fair boards and veterinarians should reexamine biosecurity recommendations for livestock exhibitions. PMID- 20590501 TI - Perceptions regarding workplace hazards at a veterinary teaching hospital. AB - OBJECTIVE: To assess perceptions of personnel working at a veterinary teaching hospital regarding risks of occupational hazards and compare those perceptions with assessments made by occupational safety experts. DESIGN: Cross-sectional study. STUDY POPULATION: A representative sample of personnel (n = 90) working at the veterinary teaching hospital at Colorado State University and a panel of 3 occupational safety experts. PROCEDURES: Hospital personnel ranked perceptions of 14 physical, chemical, and biological workplace hazards and listed the injuries, illnesses, and near misses they had experienced. The expert panel provided consensus rankings of the same 14 hazards for 9 sections of the facility. Risk perceptions provided by the 2 sources were compared. RESULTS: Risk perceptions did not differ significantly between hospital personnel and the expert panel for most of the site-specific comparisons (94/126 [75%]). Personnel perceived greater risks for some physical hazards (loud noises, sharps injuries, and ionizing radiation) and some chemical or materials exposures (insecticides or pesticides and tissue digester emissions). In contrast, the expert panel perceived greater risks for physical hazards (bite or crush and restraining and moving animals), chemical exposures (anesthetic waste gas), and biological exposures (Toxoplasma gondii, antimicrobial-resistant bacteria, and allergens). CONCLUSIONS AND CLINICAL RELEVANCE: Participants and safety experts had similar perceptions about occupational risks, but there were important differences where hospital personnel apparently overestimated or underappreciated the risks for workplace hazards. This type of study may be useful in guiding development of optimal workplace safety programs for veterinary hospitals. PMID- 20590502 TI - Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors. AB - Stroke is one of the most common causes of death and long term disability throughout the world. It may be the outcome of a number of monogenic disorders or, more commonly, a polygenic multifactorial disease. Numerous studies have investigated the role of genetics in the pathogenesis of ischemic stroke, with varied and often contradictory results. The candidate 'stroke risk' genes affecting haemostasis (F5, F2, FGA/FGB, F7, F13A1, vWF, F12, SERPINE1, ITGB3/ITGA2B, ITGA2, GP1BA, TPA, TAFI, THBD, PZ, ANX5), homocysteine metabolism (MTHFR, CBS, MTR), and lipid metabolism (apo E, LPL, CETP, ABCA1, apo AI, apo CIII, apo AIV, apo AV, apo B, apo H, apo(a), PON1/2/3, LDLR/LOX-1) are evaluated in this review. By examining meta-analyses and case-control studies, we made a classification of gene/gene polymorphisms according to the degree of association with ischemic stroke risk. The data assembled could be very useful for further meta-analysis and for future clinical applications. PMID- 20590503 TI - Low maternal PAPP-A is associated with small-for-gestational age newborns and stillbirths. AB - We investigated the association of first trimester low maternal serum pregnancy associated plasma protein-A (PAPP-A) levels with small-for-gestational age (SGA) newborns and stillbirths (SBs) in a retrospective national population-based register study. The study group comprised 921 women with the lowest 5% PAPP-A levels (< or =0.3 MoM) and the control group comprising 18,615 women with PAPP-A levels >0.3 MoM. In the study group there were 35 (3.8%) and in the control group 213 SGA newborns (1.1%), respectively (OR, 3.41; 95% CI, 2.37-4.91). There were 9 (1.0%) and 51 (0.3%) cases of SBs in the study and control groups, respectively (p < 0.002; OR, 3.59; 95% CI, 1.76-7.32). Low PAPP-A is a risk factor for SGA and SB. PMID- 20590504 TI - Efficacy of intrauterine lignocaine plus vaginal misoprostol for pain relief in premenopausal women undergoing endometrial aspiration and ambulatory hysteroscopy. AB - OBJECTIVE: To compare the effectiveness of a combination of intrauterine lignocaine and vaginal misoprostol in reducing pain at hysteroscopy and endometrial aspiration (EA). DESIGN: Prospective randomized trial (Canadian Task Force Classification I). SETTING: Tertiary care referral hospital. POPULATION: Forty-nine premenopausal women undergoing hysteroscopy plus EA. METHODS: Patients were randomized into misoprostol plus intrauterine lignocaine group (Group I) and only misoprostol group (Group II). MAIN OUTCOME MEASURES: Pain scores at hysteroscope insertion (T (time) 1), during and after hysteroscopy (T2, T3), during EA (T4), 15 minutes after the procedure (T5) and at discharge (T6). Satisfaction and procedure acceptability was assessed by a questionnaire. RESULTS: The mean age of patients in Group I and Group II was 35.4 +/- 8.6 years and 38.9 +/- 13.2 years, respectively. The mean pain scores in Group I were 23.6% lower at T2 and 27% lower at T4 when compared with Group II; the difference of latter being significant. CONCLUSION: A combination of intrauterine lignocaine plus vaginal misoprostol reduced the pain score in premenopausal women undergoing hysteroscopy and EA. PMID- 20590506 TI - Validation of the patient activation measure in a multiple sclerosis clinic sample and implications for care. AB - PURPOSE: Patient engagement in multiple sclerosis (MS) care can be challenging at times given the unpredictable disease course, wide range of symptoms, variable therapeutic response to treatment and high rates of patient depression. Patient activation, a model for conceptualising patients' involvement in their health care, has been found useful for discerning patient differences in chronic illness management. The purpose of this study was to validate the patient activation measure (PAM-13) in an MS clinic sample. METHODS: This was a survey study of 199 MS clinic patients. Participants completed the PAM-13 along with measures of MS medication adherence, self-efficacy, depression and quality of life. RESULTS: Results from Rasch and correlation analyses indicate that the PAM-13 is reliable and valid for the MS population. Activation was associated with MS self-efficacy, depression and quality of life but not with self-reported medication adherence. Also, participants with relapse-remitting MS, current employment, or high levels of education were more activated than other subgroups. CONCLUSIONS: The PAM-13 is a useful tool for understanding health behaviours in MS. The findings of this study support further clinical consideration and investigation into developing interventions to increase patient activation and improve health outcomes in MS. PMID- 20590507 TI - I can't sleep at night with discharging this lady: The personal impact of ending therapy on speech-language pathologists. AB - The ending of therapy is a crucial time for speech-language pathologists and can impact on their sense of achievement and satisfaction. Drawing on literature from psychotherapy, social work and rehabilitation as well as from the area of aphasia therapy, this paper explores how speech-language pathologists juggle the tensions of coping with real versus ideal endings, of managing the building of close therapeutic relationships which then have to be broken, and of balancing a respect for client autonomy while retaining control over caseloads and fair allocation of resources. I suggest that the way in which therapy finishes reflects a merger of how clinicians manage these tensions. Clinicians may benefit from a greater recognition of what they do and feel at discharge, not only to further reflective practice, but also to encourage more sensitive involvement with both clients and students. PMID- 20590508 TI - The end of an affair: Discharging clients from speech-language pathology. AB - This paper expands on the lead article by Hersh (2010) regarding a number of challenges that face speech-language pathologists (SLPs) when ending therapy, in this case focusing on children's speech and language impairment. Children's speech and language impairments are often long-term with impacts on other aspects of their functioning; there is little clarity about the notion of resolution and there is little research about optimum points of discharge or ending therapy. In the lead article, Hersh (2010) reports the personal concerns experienced by SLPs working with people with aphasia. Similar findings are highlighted here from the child speech and language impairment context; in particular that SLPs' thresholds of concern vary. The paper notes the resource pressures that lead to prioritization decisions related to the point of discharge and argues that clarity in goal planning and the explicit discussion of goals and the purpose of intervention, in partnership with clients and their families goes some way to reducing pressure faced by SLPs. PMID- 20590509 TI - Discharge experiences of speech-language pathologists working in Cyprus and Greece. AB - Post-termination relationships are complex because the client may need additional services and it may be difficult to determine when the speech-language pathologist-client relationship is truly terminated. In my contribution to this scientific forum, discharge experiences from speech-language pathologists working in Cyprus and Greece will be explored in search of commonalities and differences in the way in which pathologists end therapy from different cultural perspectives. Within this context the personal impact on speech-language pathologists of the discharge process will be highlighted. Inherent in this process is how speech-language pathologists learn to hold their feelings, anxieties and reactions when communicating discharge to clients. Overall speech language pathologists working in Cyprus and Greece experience similar emotional responses to positive and negative therapy endings as speech-language pathologists working in Australia. The major difference is that Cypriot and Greek therapists face serious limitations in moving their clients on after therapy has ended. PMID- 20590510 TI - They can because they think they can. AB - Based on interviews with practising speech and language therapists, Hersh (2010) identifies three key areas that constitute challenging aspects of ending therapy, fundamentally to do with client and clinician expectations of what therapy has to offer, managing therapy relationships that need to be robust yet temporary, and balancing client empowerment with the need to achieve fair distribution of resources. In this commentary I take a closer look at the first two of these aspects by dissecting an incident from my own therapy experience. I highlight particularly the importance of the way therapy is set up to the way in which it ends. Given the increasing importance attributed to client involvement in decisions regarding therapy, I also reflect briefly on the centrality of established evaluation measures to the potential for achieving informed consent and informed participation. PMID- 20590511 TI - Beginning of the end? Ending the therapeutic relationship in palliative care. AB - Hersh (2010) raises important issues regarding the ending of the therapeutic relationship. In this paper, we will explore this concept in relation to speech language pathology (SLP) and palliative care. Palliative care aims to affirm life and minimize the complications of life limiting disease. Speech-language pathologists (SLPs) work with people with progressive and life limiting disease as rehabilitation experts but often work independently of specialist palliative care teams. Rehabilitation may seem incongruent with palliation but SLPs have a vital role in the empowerment of patients with communication difficulties and symptom reduction through specialist dysphagia management and communication therapy. This is vital in the last months and weeks of life. Starting and closing episodes of care remains a challenging area for therapists. SLP membership of palliative care multidisciplinary teams is limited and there may be a lack of understanding between professionals regarding the SLP role. In this paper we will use case studies and the palliative care literature to define a role for rehabilitation and the transition from supportive to palliative rehabilitation and closing episodes of care. PMID- 20590512 TI - The therapeutic relationship once established, need never be broken. AB - In the lead article, Hersh (2010) draws attention to the significant phase of ending therapy for clients and in particular, for their therapists. Hersh highlights three main tensions that underpin this process: real versus ideal endings, making and breaking of the therapeutic relationship, and balancing of respect for client autonomy over considerations of caseload and resources. In this paper, I offer a commentary on the first two of these issues by drawing upon my experience as a speech-language pathologist/family therapist specializing in voice, and as an academic fostering the development of student clinicians. This is then linked to parallel discussions in the recent psychoanalytic and psychotherapy literature. I support Hersh's premise that the implicit processes and emotions associated with this final phase of therapy need to be made more explicit and suggest that this is more likely to occur when clinicians acknowledge that they too experience rewards and losses in the therapeutic relationship. I challenge the notion that any therapeutic relationship once established is ever entirely broken. PMID- 20590513 TI - Preparation for ending therapeutic relationships. AB - The affective components that arise as speech-language pathologists (SLPs) interact with the clients they serve and how these factors impact the process of ending therapy and SLPs' job satisfaction were discussed within the lead article to this scientific forum (Hersh, 2010 ). The development of a decision-making paradigm for dismissal is an expected outcome of training programs for SLP students, but this area may need more emphasis in the curriculum. Graduate students in the United States often complete practicum experiences in 10-12 weeks. Their assignments may require continuing an intervention program initiated by others, and they generally move to another practicum site before their patients' dismissal. This training schedule may limit the opportunities to develop a solid foundation in dismissal guidelines and practices unless this area is emphasized. Increased efforts to engage students in focused discussions about patient dismissal from the time treatment is initiated might lead to greater confidence in making these decisions independently after graduation. Discussions of dismissal should include case load management, service delivery models, review of practice guidelines from credentialing organizations and funding sources. Development of the counseling skills needed to promote improved understanding of the affective components that impact both SLPs and their patients must be cultivated. PMID- 20590514 TI - Discharging patients: A perspective from speech-language pathologists working in public hospitals in Malaysia. AB - Speech-language pathologists (SLPs) practising in Malaysia face similar dilemmas as their counterparts in more developed countries when it comes to deciding on discharge/termination of services for their patients. Furthermore, discharge dilemmas appear to be a frequent and inevitable part of their everyday practice. In an interview conducted for the purpose of this paper, it was clear that many SLPs found it difficult to articulate or justify the process they took to reach a decision on whether or not to terminate their services or discharge their patients. Much of the difficulty is anchored on the need to be realistic and function within the confines of limited resources. Malaysian SLPs were aware of the ideals that had to be abandoned along the way but had not allowed guilt to dissuade or discourage them from providing what they perceived as the next best available service. The not-so ideal decisions made by these SLPs may be frowned upon by international standards but must be examined within the local historical perspective of the development of the SLP profession in Malaysia. The dilemma will continue until the country produces SLPs in sufficient numbers but the profession is reminded that less-than-ideal practices may perpetuate over time into unhealthy traditions that will require major efforts to be undone. PMID- 20590515 TI - The dilemma of discharge and some possible solutions. AB - Discharging clients with acquired brain injury can be a challenging process for all parties involved. In this response to Hersh (2010), three issues are raised which are relevant to the discussion of discharge and may offer some solutions to the dilemmas faced during this time. The first issue is that discharge may not always be necessary depending on the service delivery model that is used. The second issue is that recent advances in experience-dependent neuroplasticity research may change the way clinicians determine treatment goals, which has implications for discharge decisions. Finally, an alternative strategy to assist with discharge is the facilitation of social engagement for the person with brain injury and their social networks. While it is acknowledged that discharge can be a positive time for some clients, it can also be a time where people feel abandoned, even bereft and, in some cases, angry. Avoiding this scenario requires forward planning from the outset of treatment and the use of strategies to ensure that the person is well supported at the time of discharge. This paper presents some of these strategies which may be useful for clinicians to consider as they plan discharge in collaboration with their clients. PMID- 20590516 TI - The experience of discharging children from phonological intervention. AB - The ultimate goal of phonological intervention is to make unintelligible speech intelligible. Discharging children who have achieved this goal can be a rewarding experience. However, given the constraints of everyday clinical practice, not all discharge experiences can be happy ones. In this paper I compare and contrast the issues raised by Hersh (2010) about the impact of ending therapy on speech language pathologists (SLPs) who work with adults who have aphasia, with SLPs who work with children who have unintelligible speech. Using the scaffold provided by Hersh (2010), I consider how ideal endings for children with phonological impairment are possible, reflect on the disheartening experience of having to discharge children before realization of the ultimate goal, examine the paradox of building authentic relationships with children and their families predestined to be broken, and, explore the dilemma of promoting client involvement in decisions while retaining professional control over the discharge process. The need to better understand the clinical expertise required to discharge children from phonological intervention in ideal and less than ideal situations is discussed. Finally, the need to determine ideal intervention intensity is addressed given the potential for children with a phonological impairment to be discharged with intelligible speech. PMID- 20590518 TI - A comparison of rural speech-language pathologists' and residents' access to and attitudes towards the use of technology for speech-language pathology service delivery. AB - This paper reports results and implications of two related studies which investigated (a) access of residents and speech-language pathologists (SLPs) of rural Australia to information and communication technologies (ICT) and (b) their attitudes towards the use of ICT for delivery of speech-language pathology services. Both studies used mail out questionnaires, followed by interviews with a subset of those who completed the questionnaires. Data were obtained from 43 questionnaires from rural residents and 10 interviews with a subset of those residents, and from questionnaires returned by 49 SLPs and 4 interviews with a subset of those SLPs. Results show a mismatch between rural residents' and SLPs' access to and attitudes towards use of ICT for speech-language pathology service delivery. Rural residents had better access and more positive attitudes to the use of ICT for speech-language pathology service delivery than expected by SLPs. The results of this study have important implications for education and professional development of SLPs and for research into the use of ICT for telespeech-language pathology. PMID- 20590519 TI - Why do students from related professions choose not to enter speech-language pathology? AB - This paper provides insight into the reasons why students from similar undergraduate professional preparation programs (education and allied health) choose not to enter the speech-language pathology (SLP) program. A survey was conducted with students of education (n = 162), occupational therapy (n = 139), physiotherapy (n = 49) and social work (n = 64). Qualitative and quantitative analyses suggested that many of the students did not know about the speech language pathology profession at the time when they selected their career or they had a limited knowledge of the scope of professional practice (e.g., identified SLP as too specific) and this may have influenced their decision making. These findings, along with recent research in regard to the factors that influence career choice in SLP, inform the SLP profession of the need for increased public education about the profession. Further, this increased need for public education becomes more vital as the profession prepares to ensure adequate number of SLPs for future service delivery in the face of increased service demands and SLP shortages. PMID- 20590520 TI - "It's not everyday that parents get a chance to talk like this": Exploring parents' perceptions and expectations of speech-language pathology services for children with intellectual disability. AB - Tailoring the delivery of disability services to the preferences and requirements of service users allows for more effective partnerships. The aim of this research was to explore parents' perceptions and the expectations of their child's speech language pathology (SLP) within an intellectual disability service. Parents of school-aged children with intellectual disability who received a SLP service in Ireland participated in the research: 17 parents participated in focus groups and 103 parents answered questionnaires. The core themes from the focus groups, which subsequently informed the questionnaire design, were: experience of the SLP service, communication difficulties, expectations of the SLP service, and future developments. The key questionnaire results indicated that parents viewed their SLP as the "expert" and viewed school-based and clinic-based services differently. Parents were more likely to believe that their child would always need therapy if they received a school-based service. Whereas, parents were more likely to think that their child's speech was improving as they got older and were more likely to be aware of therapy activities if therapy was clinic-based. The findings have implications for the delivery of SLP services suggesting that clarification of parents' roles and expectations are required. PMID- 20590521 TI - I-131 tositumomab. AB - IMPORTANCE OF THE FIELD: Follicular lymphoma (FL) is a subgroup of B-cell Non Hodgkin's lymphomas (NHL) that account for 15 - 30% of all lymphomas. I-131 tositumomab is a radiommunoconjugate of (131)I and the anti-CD20 monoclonal antibody tositumomab. It is one of two available radioimmunoconjugates for the treatment of recurrent, refractory, or transformed FL. AREAS COVERED IN THIS REVIEW: This review describes the clinical pharmacology of I-131 tositumomab, dosing and administration guidelines, and the key clinical trials providing evidence of its efficacy and safety in patients with FL, transformed, or other aggressive B-NHL, in combination with chemotherapy, or its incorporation in transplant conditioning regimens. This review also covers safety and regulatory concerns regarding the use of I-131 tositumomab. WHAT THE READER WILL GAIN: This review critically appraises the clinical trials behind approval of I-131 tositumomab as a second-line agent for FL and also outlines the data supporting its use in the upfront setting. TAKE HOME MESSAGE: I-131 tositumomab is a safe and effective option for patients with recurrent, refractory, or transformed FL and carries promise in the upfront treatment of FL, aggressive B-NHL, and as a transplant conditioning regimen. PMID- 20590522 TI - Biphasic calcium phosphate microparticles for bone formation: benefits of combination with blood clot. AB - Particulate forms of biphasic calcium phosphate (BCP) biomaterials below 500 MUm are promising bone substitutes that provide with interconnected open porosity allowing free circulation of fluids and cells. Dispersion of the particles in the surrounding tissues at the time of implantation is a major drawback preventing from an easy use. We have asked whether blood clot could be a convenient natural hydrogel for handling BCP microparticles, and we hypothesized that blood clot might also confer osteoinductive properties to these particles. We show here that blood clotted around BCP microparticles constitutes a cohesive, moldable, and adaptable biomaterial that can be easily implanted in subcutaneous sites but also inserted and maintained in segmental bone defects, conversely to BCP microparticles alone. Moreover, implantation in bony and ectopic sites revealed that this composite biomaterial has osteogenic properties. It is able to repair a 6-mm critical femoral defect in rat and induced woven bone formation after subcutaneous implantation. Parameters such as particle size and loading into the clot are critical for its osteogenic properties. In conclusion, this blood/BCP microparticle composite is a moldable and osteoinductive biomaterial that could be used for bone defect filling in dental and orthopedic surgery. PMID- 20590523 TI - Spinal microvascular expression of PV-1 is associated with inflammation, perivascular astrocyte loss, and diminished EC glucose transport potential in acute SCI. AB - The endothelial-specific expression of plasmalemmal vesicle associated protein-1 (PV-1) is typical of fenestrated endothelium observed in pulmonary capillaries and some endocrine organs. In the central nervous system (CNS) it is expressed during development but disappears concomitant with maturation of the blood-CNS barrier [1]. Consistent with observations made in models of stroke, Alzheimer's disease, and tumorigenesis, we show PV-1 expression in the spinal cord specifically upregulated by pathologically-activated endothelial cells (ECs) in response to traumatic spinal cord injury (SCI). Adult female C57Bl/6 mice received a moderate T9/10 contusive SCI. PV-1 assessed by qRT-PCR and immunohistochemistry 3 hours to 14 days post-injury showed expression as early as 1 day post-SCI, with levels decreasing by 14 days. This expression was associated with microvessels in the injury epicenter and penumbral zone, with the time course and distribution correlated with progressing peripheral inflammatory cell infiltration. PV-1-immunoreactive ECs were angiogenic as demonstrated by intravascular binding of Griffonia simplicifolia isolectin B4 (IB4). ECs expressing high levels of PV-1 were anatomically and physiologically abnormal with altered/absent immunostaining for occludin and zonula occludens-1 (ZO-1), and decreased expression of glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4). Glucose transporter type I (Glut-1) expression decreased in affected, PV-1 positive microvessels with little colocalization of PV-1 and Glut-1 apparent by 7 days post-SCI. These data suggest that upregulation of microvascular expression of PV-1 post-SCI may promote major components of secondary injury including extravasation of cellular and acellular mediators of inflammation and may accelerate loss of neuropil and decline in the functional and anatomical integrity of the neurovascular unit (NVU). PMID- 20590524 TI - Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents. AB - Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic. PMID- 20590525 TI - p38(MAPK)/p53 signalling axis mediates neuronal apoptosis in response to tetrahydrobiopterin-induced oxidative stress and glucose uptake inhibition: implication for neurodegeneration. AB - BH4 (tetrahydrobiopterin) induces neuronal demise via production of ROS (reactive oxygen species). In the present study we investigated the mechanisms of its toxicity and the redox signalling events responsible for the apoptotic commitment in SH-SY5Y neuroblastoma cells and in mouse primary cortical neurons. We identified in p38(MAPK)/p53 a BH4-responsive pro-apoptotic signalling axis, as demonstrated by the recovery of neuronal viability achieved by gene silencing or pharmacological inhibition of both p38(MAPK) and p53. BH4-induced oxidative stress was characterized by a decrease in the GSH/GSSG ratio, an increase in protein carbonylation and DNA damage. BH4 toxicity and the redox-activated apoptotic pathway were counteracted by the H2O2-scavengers catalase and N acetylcysteine and enhanced by the GSH neo-synthesis inhibitor BSO (buthionine sulfoximine). We also demonstrated that BH4 impairs glucose uptake and utilization, which was prevented by catalase administration. This effect contributes to the neuronal demise, exacerbating BH4-induced nuclear damage and the activation of the pro-apoptotic p38(MAPK)/p53 axis. Inhibition of glucose uptake was also observed upon treatment with 6-hydroxydopamine, another redox cycling molecule, suggesting a common mechanism of action for auto-oxidizable neurotoxins. PMID- 20590527 TI - Enantioselective reduction of prochiral ketones by engineered bifunctional fusion proteins. AB - NADPH-dependent oxidoreductases are useful catalysts for the production of chiral synthons. However, preparative applications of oxidoreductases require efficient methods for in situ regeneration of the expensive nicotinamide cofactors. An advantageous method for cofactor regeneration is the construction of bifunctional fusion proteins composed of two enzymes, one catalysing the reduction reaction and the other one mediating the recycling of cofactors. Herein, we describe the in-frame fusion between an NADP+-accepting mutant of FDH (formate dehydrogenase) from Mycobacterium vaccae N10 and KR [3-ketoacyl-(acyl-carrier-protein) reductase] from Synechococcus sp. strain PCC 7942. The generation of linker insertion mutants led to a fusion protein exhibiting 100 and 80% of the enzymatic activities of native KR and FDH respectively. Escherichia coli cells expressing the fusion protein showed an approx. 2-fold higher initial reaction rate in the production of chiral alcohols than cells expressing the enzymes separately. The application of the engineered fusion protein in whole-cell bioreduction of pentafluoroacetophenone resulted in a substrate conversion of 99.97% with an excellent enantiomeric excess of 99.9% (S)-1-(pentafluorophenyl)ethanol. PMID- 20590526 TI - Distribution and paralogue specificity of mammalian deSUMOylating enzymes. AB - The covalent attachment of SUMO (small ubiquitin-like protein modifier) to target proteins results in modifications in their activity, binding interactions, localization or half-life. The reversal of this modification is catalysed by SENPs (SUMO-specific processing proteases). Mammals contain four SUMO paralogues and six SENP enzymes. In the present paper, we describe a systematic analysis of human SENPs, integrating estimates of relative selectivity for SUMO1 and SUMO2, and kinetic measurements of recombinant C-terminal cSENPs (SENP catalytic domains). We first characterized the reaction of each endogenous SENP and cSENPs with HA-SUMO-VS [HA (haemagglutinin)-tagged SUMO-vinyl sulfones], active-site directed irreversible inhibitors of SENPs. We found that all cSENPs and endogenous SENP1 react with both SUMO paralogues, whereas all other endogenous SENPs in mammalian cells and tissues display high selectivity for SUMO2-VS. To obtain more quantitative data, the kinetic properties of purified cSENPs were determined using SUMO1- or SUMO2-AMC (7-amino-4-methylcoumarin) as substrate. All enzymes bind their respective substrates with high affinity. cSENP1 and cSENP2 process either SUMO substrate with similar affinity and catalytic efficiency; cSENP5 and cSENP6 show marked catalytic specificity for SUMO2 as measured by Km and kcat, whereas cSENP7 works only on SUMO2. Compared with cSENPs, recombinant full-length SENP1 and SENP2 show differences in SUMO selectivity, indicating that paralogue specificity is influenced by the presence of the variable N-terminal domain of each SENP. Our data suggest that SUMO2 metabolism is more dynamic than that of SUMO1 since most SENPs display a marked preference for SUMO2. PMID- 20590528 TI - Bimolecular fluorescence complementation analysis of eukaryotic fusion products. AB - BACKGROUND INFORMATION: Cell fusion is known to underlie key developmental processes in humans and is postulated to contribute to tissue maintenance and even carcinogenesis. The mechanistic details of cell fusion, especially between different cell types, have been difficult to characterize because of the dynamic nature of the process and inadequate means to track fusion products over time. Here we introduce an inducible system for detecting and tracking live cell fusion products in vitro and potentially in vivo. This system is based on BiFC (bimolecular fluorescence complementation) analysis. In this approach, two proteins that can interact with each other are joined to fragments of a fluorescent protein and are expressed in separate cells. The interaction of said proteins after cell fusion produces a fluorescent signal, enabling the identification and tracking of fusion products over time. RESULTS: Long-term tracking of fused p53-deficient cells revealed that hybrid cells were capable of proliferation. In some cases, proliferation was preceded by nuclear fusion and division was asymmetric (69%+/-2% of proliferating hybrids), suggesting chromosomal instability. In addition, asymmetric division following proliferation could give rise to progeny indistinguishable from unfused counterparts. CONCLUSIONS: These results support the possibility that the chromosomal instability characteristic of tumour cells may be incurred as a consequence of cell fusion and suggest that the role of cell fusion in carcinogenesis may have been masked to this point for lack of an inducible method to track cell fusion. In sum, the BiFC-based approach described here allows for comprehensive studies of the mechanism and biological impact of cell fusion in nature. PMID- 20590529 TI - Dual roles for MEF2A and MEF2D during human macrophage terminal differentiation and c-Jun expression. AB - Recent reports have evidenced a role for MEF2C (myocyte enhancer factor 2C) in myelopoiesis, although the precise functions of this transcription factor are still unclear. We show in the present study that MEF2A and MEF2D, two other MEF2 family members, are expressed in human primary monocytes and in higher amounts in monocyte-derived macrophages. High levels of MEF2A-MEF2D heterodimers are found in macrophage-differentiated HL60 cells. Chromatin immunoprecipitations demonstrate that MEF2A is present on the c-Jun promoter, both in undifferentiated and in macrophage-differentiated cells. Moreover, c-Jun expression is derepressed in undifferentiated cells in the presence of HDAC (histone deacetylase) inhibitor, indicating the importance of chromatin acetylation in this process. We show that MEF2A/D dimers strongly interact with HDAC1, and to a lesser extent with HDAC7 in macrophages, whereas low levels of MEF2A/D-HDAC1 complexes are found in undifferentiated cells or in monocytes. Since trichostatin A does not disrupt MEF2A/D-HDAC1 complexes, we analysed the potential interaction of MEF2A with p300 histone acetyltransferase, whose expression is up-regulated in macrophages. Interestingly, endogenous p300 only associates with MEF2A in differentiated macrophages, indicating that MEF2A/D could activate c-Jun expression in macrophages through a MEF2A/D-p300 activator complex. The targets of MEF2A/D-HDAC1-HDAC7 multimers remain to be identified. Nevertheless, these data highlight for the first time the possible dual roles of MEF2A and MEF2D in human macrophages, as activators or as repressors of gene transcription. PMID- 20590530 TI - Effects of exercise training on adipogenesis of stromal-vascular fraction cells in rat epididymal white adipose tissue. AB - AIM: Previous studies have shown that exercise training reduced white adipose tissue (WAT) mass compared to that in sedentary controls, and that the smaller mass contained fewer adipocytes. However, the effect of exercise training on adipogenesis is not completely clear. Therefore, we re-examined the effect of exercise training on adipocyte numbers in WAT and, if such an effect was found tested the adipogenic responses of stromal-vascular fraction (SVF) cells containing adipose tissue-derived stem cells (ADSC) in epididymal WAT from exercise-trained (TR) rats. METHODS: Wistar male rats were divided into two groups: control (C) and TR. The TR rats were subjected to exercise on a treadmill for 9 weeks. SVF cells containing ADSC were separated from epididymal WAT by centrifugation. Expression of adipocyte differentiation-related genes and adipogenesis of SVF cells were examined. RESULTS: In SVF cells of TR rats, the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and that of PPARgamma target lipogenic genes was dramatically downregulated, whereas that of preadipocyte factor-1 gene was significantly upregulated. Lipid accumulation in SVF cells of TR rats after the induction of adipocyte differentiation was significantly suppressed in comparison with that of C rats. Moreover, increased expression of hypoxia-inducible factor-1alpha (HIF-1alpha) protein was observed in SVF cells of TR rats. Pre-treatment of YC-1, a potent HIF 1alpha inhibitor, in SVF cells of TR rats restored adipogenesis. CONCLUSION: These results suggest that exercise training suppresses the ability of SVF cells to differentiate into adipocytes, and that underlying mechanisms involve the upregulation of HIF-1alpha expression. PMID- 20590531 TI - The effect of desflurane on filtration performance of breathing system filters. AB - This study assessed the effect of desflurane on the filtration performance of six breathing system filters intended for use with adults. Three filters contained an electrostatic filter material and three contained a pleated glass fibre filter material. Five samples of each model of filter were exposed to 6% v/v of desflurane for 1 h, 12% v/v of desflurane for 1 h, 12% v/v of desflurane for 4 h and air only for 1 h. Five samples of each filter were also tested without exposure to any vapour or air. The filtration performance was measured by challenging each filter with an aerosol of sodium chloride particles using a Moore's test rig. Penetration of particles through the electrostatic filters increased following exposure to a higher concentration of desflurane for a longer duration (p < 0.001). The effect on two of the pleated filters was not significant (p = 0.55 and p = 0.64). The effect on the remaining pleated filter was significant (p < 0.001) but small. The efficiency of some filters decreases when they are exposed to high concentrations of desflurane for a long duration. This effect appears more marked in electrostatic filters compared with pleated filters. PMID- 20590532 TI - Whole-genome association study for fatty acid composition of oleic acid in Japanese Black cattle. AB - Fatty acid composition, especially oleic acid (C18:1), plays an important role in the eating quality of meat in Japanese Black cattle. Therefore, the objective of this study was to identify loci associated with C18:1 in the intramuscular fat of the trapezius muscles in Japanese Black cattle using the Illumina BovineSNP50 BeadChip whole genome single nucleotide polymorphism (SNP) assay. We also evaluated the relationship between C18:1 and three fatty acid synthesis genes, fatty acid synthase (FASN), stearoyl-CoA desaturase and sterol regulatory element binding protein-1. In this experiment, we applied a mixed model and Genomic Control approach using selective genotyping to perform a genome-wide association study. A total of 160 animals (80 animals with higher values and 80 animals with lower values), selected from 3356 animals based on corrected phenotype, were genotyped using the Illumina BovineSNP50 BeadChip and three fatty acid synthesis genes, and the quality of these SNPs was assessed. In this study, a total of 38 955 SNPs, which included SNPs in the three fatty acid synthesis genes, were used, and the estimated inflation factor was 1.06. In the studied population, a total of 32 SNPs, including the FASN gene, had significant effects, and in particular 30 SNPs of all significant SNPs were located between 49 and 55 Mbp on chromosome 19. This study is one of the first genome-wide association studies for fatty acid composition in a cattle population using the recently released Illumina BovineSNP50 BeadChip. PMID- 20590533 TI - Prophylactic dietary restriction may promote functional recovery and increase lifespan after spinal cord injury. AB - Functional recovery after spinal cord injury (SCI) is limited, and the injury results in a dramatic reduction in long-term lifespan. Prophylactic dietary restriction (DR) robustly extends animal lifespan, and is beneficial in models of neuronal insult. In rats, we found that one form of DR, every-other-day-fasting (EODF), which started 1 month prior to a cervical SCI improved functional recovery, resulted in greater numbers of neurons surrounding the injury site, and a approximately 45% reduction in lesion size compared to the control group. In the light of the low-risk implementation of prophylactic EODF, the clinical translation as a treatment prior to elective subacute or chronic interventions is attractive. There are numerous secondary complications after human SCI, including a 13- to 25-year reduction in lifespan. DR consistently increases median and maximal lifespan in a large range of organisms, including non-human primates. Animal research suggests that EODF might reduce many of the secondary complications people with SCI suffer from. Dietary interventions may provide the possibility to improve the quality and span of life for individuals with SCI. PMID- 20590535 TI - Anti-Nogo on the go: from animal models to a clinical trial. AB - Small lesions of the adult central nervous system (CNS) often have a good prognosis with extensive functional recovery based in part on spontaneous neuritic sprouting and rearrangements of projections. This is well documented for the cortex, but these changes can also occur in the spinal cord. Nogo-A is a protein present in CNS myelin that inhibits neurite growth. Models of spinal cord injury (SCI) in rats and macaque monkeys demonstrate that treatment with function blocking antibodies of Nogo-A results in an upregulation of growth-specific proteins, enhanced regenerative and compensatory sprouting of fibers, and the formation of new functional connections in the spinal cord. In animals with unilateral sensorimotor cortex lesions followed by Nogo-A antibody treatment, fibers from the intact corticofugal system crossed the midline, supplying innervation to the denervated brain stem or spinal cord. Behavioral tests showed marked improvements of functional recovery in the Nogo-A antibody treated spinal cord- or brain-injured animals. A Phase I clinical trial applying anti-Nogo-A antibody to subjects with acute SCI has been successfully conducted and a multicentric, multinational Phase II trial is currently in preparation. PMID- 20590534 TI - Reflex conditioning: a new strategy for improving motor function after spinal cord injury. AB - Spinal reflex conditioning changes reflex size, induces spinal cord plasticity, and modifies locomotion. Appropriate reflex conditioning can improve walking in rats after spinal cord injury (SCI). Reflex conditioning offers a new therapeutic strategy for restoring function in people with SCI. This approach can address the specific deficits of individuals with SCI by targeting specific reflex pathways for increased or decreased responsiveness. In addition, once clinically significant regeneration can be achieved, reflex conditioning could provide a means of reeducating the newly (and probably imperfectly) reconnected spinal cord. PMID- 20590537 TI - Abstracts of the 16th World Congress of Basic and Clinical Pharmacology. July 17 23, 2010. Copenhagen, Denmark. PMID- 20590536 TI - Clinical pharmacology in research, teaching and health care: Considerations by IUPHAR, the International Union of Basic and Clinical Pharmacology. PMID- 20590538 TI - Percentage of positive biopsies predicts lymph node involvement in men with low risk prostate cancer undergoing radical prostatectomy and extended pelvic lymphadenectomy. AB - OBJECTIVE: To evaluate preoperative predictive risk factors associated with lymph node metastases (LNM) in a cohort of low-risk prostate cancer (PCA) patients. PATIENTS AND METHODS: The charts of 499 patients were retrospectively reviewed to identify prognostic risk factors for the presence of LNM. Pathohistological data and Gleason score of the radical prostatectomy (RP) specimen, number of removed nodes, number of positive lymph nodes, and anatomical distribution of LNM were tabulated and evaluated. A correlation between clinical stage, preoperative serum prostate-specific antigen (PSA), biopsy Gleason score, number of biopsies taken, percentage of positive biopsies and the presence of LNM were calculated. All 499 men underwent retropubic RP and extended pelvic lymphadenectomy (EPLND). RESULTS: LNM were identified in 29 (5.8%) patients. A prediction model based on clinical stage, PSA, and biopsy Gleason score had a predictive accuracy of 79.2%. The addition of number of positive biopsies and % positive cores improved its predictive accuracy to 81.5% and 87.8%, respectively. The predicted frequency of LNM by the original nomogram was 7.4% and differed by less than 3% with the actual observation of LNM. The predictive accuracy of the nomogram was 81.5% as compared with 87.8% of the prediction model of this study. CONCLUSIONS: The percentage of positive cores involved with PCA is the most reliable predictor of LNM and indicates the need for EPLND. The Briganti nomogram has been validated and a general applicability for predicting the presence of LNM was proven. PMID- 20590539 TI - Predictors of morbidity in patients with indwelling ureteric stents: results of a prospective study using the validated Ureteric Stent Symptoms Questionnaire. AB - OBJECTIVE: To assess the predictors of morbidity in patients with indwelling ureteric stents using a validated questionnaire. PATIENTS AND METHODS: Eighty-six consecutive patients with indwelling double-J ureteric stent of different length and size enrolled at an Italian tertiary academic centre were prospectively evaluated with the Italian-validated Ureteric Stent Symptoms Questionnaire (USSQ), which explores the stent-related symptoms in six domains. Ureteric stents were placed for benign ureteric obstruction or after uncomplicated ureterorenoscopy, and were all removed after 28 days. The questionnaire was administered on days 7 and 28 after stent placement and on day 28 after removal. A plain abdominal X-ray was performed on days 7 and 28 after placement to determine stent location. Univariable and multivariable analyses tested the association of patient age, sex and body mass index (BMI), and stent side, length, calibre and distal loop location, with the index score of the various domains on days 7 and 28. RESULTS: All patients completed the study. At multivariable analysis, on day 7, sex, BMI and stent calibre were significantly associated with one domain (general health, body pain and work performance, respectively), while location of stent distal loop was significantly associated with five domains (urinary symptoms, body pain, general health, work performanc, and sexual matters). On day 28, body mass index was significantly associated with two domains (body pain and general health), while location of stent distal loop remained significantly associated with the same five domains (urinary symptoms, body pain, general health, work performance and sexual matters). CONCLUSION: Location of stent distal loop with respect to midline had the strongest association with most domains of the USSQ on both days 7 and 28 after stent placement. The visualization of stent distal loop crossing the midline may therefore identify patients at higher risk of post-procedural morbidity requiring early management. PMID- 20590540 TI - Detection of urinary leakage after radical retropubic prostatectomy by contrast enhanced ultrasound - do we still need conventional retrograde cystography? AB - INTRODUCTION: To prospectively evaluate the accuracy of transvesical contrast enhanced ultrasound (CEUS) as an alternative method for the detection of anastomotic leakage after radical retropubic prostatectomy (RRP) in comparison with the current standard method of conventional retrograde cystography (CG). PATIENTS AND METHODS: Forty-three patients underwent RRP for histologically proven localized prostate cancer. The vesico-urethral anastomosis was evaluated 8 days after RRP by CG and CEUS. Any peri-anastomotic leakage was assessed and determined in CG and CEUS as follows: no extravasation (EV), small leakage (<=0.5 cm), moderate leakage (>0.5 cm to <=2 cm), large leakage (>2 cm diameter of EV seen). RESULTS: In total, 21 (49%) patients showed a watertight anastomosis. Ten (23%), two (4.7%) and ten (23%) patients showed a small, intermediate and large EV, respectively. In 31 cases (72%) there was 100% agreement of CG and CEUS for detection of no, moderate and large EV, respectively. In nine cases a small and in two cases a moderate EV was categorized as watertight anastomosis by CEUS. Only in one case did CG detect a small EV where a large EV was detected in CEUS. The agreement between both methods was 95% for detecting absence or large leakages. CONCLUSION: CEUS is a promising imaging modality that seems to be equivalent to CG for detecting the presence of a large anastomotic leakage that is clinically relevant for postoperative persistence of the indwelling catheter. CEUS could be a cheap and time-saving alternative to the CG without exposure of the patient to radiation. PMID- 20590541 TI - Laterality of nephrocalcinosis in kidney stone formers with severe hypocitraturia. AB - OBJECTIVE To examine the hypothesis that the distribution of nephrocalcinosis in patients with severe hypocitraturia should be symmetric. PATIENTS AND METHODS Patients with profound hypocitraturia defined as a 24-h urine citrate < 50 mg at the time of initial presentation were identified from the metabolic stone clinic database at our academic medical center. Two independent blinded reviewers evaluated all of the abdominal radiographs for the segmental distribution of macroscopic nephrocalcinosis. RESULTS A total of 44 patients met study criteria, with an equal distribution of males and females and a mean age of 55.4 +/- 13.7 years. Mean urinary citrate was 28 +/- 11 mg/day. Nephrocalcinosis was present in at least one renal segment in 22 patients (50%). Of the 22 patients with nephrocalcinosis, 9 patients (41%) had unilateral nephrocalcinosis and 13 patients (59%) had bilateral nephrocalcinosis. Of the 35 kidneys with nephrocalcinosis, 14 kidneys (40%) had nephrocalcinosis in only one renal segment, 13 kidneys (37%) had nephrocalcinosis in two segments and eight kidneys (23%) had nephrocalcinosis involving all three segments. CONCLUSIONS Despite the systemic nature of severe hypocitraturia, nephrocalcinosis is frequently asymmetric and focal in nature. This suggests that local factors intrinsic to the renal medullary interstitium, such as vascular injury, must play a role in the formation of nephrocalcinosis. Further study to elucidate these intrinsic local factors may further improve the treatment and prevention of urinary stone disease. PMID- 20590542 TI - Mortality trends for benign prostatic hyperplasia and prostate cancer in English populations 1979-2006. AB - OBJECTIVE To determine mortality trends for benign prostatic hyperplasia (BPH) and prostate cancer in English populations, between 1979 and 2006. SUBJECTS AND METHODS Analysis of datasets that include both the underlying cause and all other mentioned causes on death certificates (together, termed 'mentions'): the Oxford Record Linkage Study, 1979-2006, and English national data, 1995-2006. RESULTS In the Oxford region, underlying-cause mortality from BPH fell from 45 deaths per million in 1979 to 2.4 in 2006. For mentions, the respective rates were 93 and 7.1. In England, underlying-cause mortality reduced from 9.2 deaths per million in 1995 to 4.5 deaths per million in 2006. For mentions, the rates were 20 and 9.9 deaths per million. When BPH was certified on death certificates, it was selected as the underlying cause of death on fewer than half. Underlying-cause mortality for prostate cancer in Oxford increased from 213 deaths per million in 1979 to 335 by 1991, and thereafter declined to 253 deaths per million in 2006. Mentions-mortality in Oxford followed a similar pattern. In later years, when there were comparable data for Oxford and England, the pattern of decline in England was similar to that in Oxford. Where mentioned, prostate cancer was coded as the underlying cause of death on three-quarters of death certificates. CONCLUSIONS The fall in BPH mortality, evident in statistics on underlying cause, was confirmed by statistics on all certified causes of death. The fall is dramatic in scale, likely to be attributable to clinical care, and could be regarded as an indicator of improving standards of care. Mortality for prostate cancer increased, peaking in the 1990s, then decreased in recent years in rates as measured both by underlying cause and by mentions. PMID- 20590543 TI - Documenting the location of prostate biopsies with image fusion. AB - OBJECTIVE To develop a system that documents the location of transrectal ultrasonography (TRUS)-guided prostate biopsies by fusing them to MRI scans obtained prior to biopsy, as the actual location of prostate biopsies is rarely known. PATIENTS AND METHODS Fifty patients (median age 61) with a median prostate specific antigen (PSA) of 5.8 ng/ml underwent 3T endorectal coil MRI prior to biopsy. 3D TRUS images were obtained just prior to standard TRUS-guided 12-core sextant biopsies wherein an electromagnetic positioning device was attached to the needle guide and TRUS probe in order to track the position of each needle pass. The 3D-TRUS image documenting the location of each biopsy was fused electronically to the T2-weighted MRI. Each biopsy needle track was marked on the TRUS images and these were then transposed onto the MRI. Each biopsy site was classified pathologically as positive or negative for cancer and the Gleason score was determined. RESULTS The location of all (n= 605) needle biopsy tracks was successfully documented on the T2-weighted (T2W) MRI. Among 50 patients, 20 had 56 positive cores. At the sites of biopsy, T2W signal was considered 'positive' for cancer (i.e. low in signal intensity) in 34 of 56 sites. CONCLUSION It is feasible to document the location of TRUS-guided prostate biopsies on pre-procedure MRI by fusing the pre-procedure TRUS to an endorectal coil MRI using electromagnetic needle tracking. This procedure may be useful in documenting the location of prior biopsies, improving quality control and thereby avoiding under-sampling of the prostate as well as directing subsequent biopsies to regions of the prostate not previously sampled. PMID- 20590544 TI - Neuromodulative treatment with percutaneous tibial nerve stimulation for intractable detrusor instability: outcomes following a shortened 6-week protocol. AB - OBJECTIVE: To describe our initial outcome data following a shortened 6-week treatment protocol with percutaneous tibial nerve stimulation (PTNS) in women with overactive bladder syndrome (OABS) unresponsive to bladder retraining and anticholinergic therapy. PATIENTS AND METHODS: This was a prospective observational study over a 6-month period. In all, 43 women with OABS refractory to medical therapy were treated with a shortened PTNS protocol that consisted of 6 weekly 30 min sessions. Bladder symptom diaries and health-related quality of life (HRQL) assessed using the short-form seven-item self-report. Incontinence Impact Questionnaire (IIQ-7) were completed before and after treatment. A positive response was defined as: (i) OAB symptoms no longer being bothersome; (ii) reduction by half in frequency episodes and (iii) reduction by 25% in IIQ-7 outcomes. RESULTS: All 43 women (median age 55.3 years) completed six treatments with a positive response rate of 69.7%. In the positive responders, the median daytime and nocturnal frequency was reduced by half after 6 weeks of treatment (11.8 vs 6.9 and 3.5 vs 1.8, respectively, P < 0.05) and the patients reported fewer urge leak episodes per 24 h (median 3.5 vs 2.4, P < 0.05). The median IIQ-7 scores improved by 25% (30.4 vs 24.3, P < 0.05) in responders, while the median number of pads changed in 24 h also decreased by 34% (3.8 vs 2.5, P < 0.05). The median acceptability of the technique when scored by Visual Analogue Score was 9.6/10 and no side-effects were reported. CONCLUSION: A shortened 6-week treatment with PTNS appears to be successful, with a significant reduction in symptoms and improvement in HRQL. This early data suggest that the duration of treatment for peripheral neuromodulation can be halved compared with the conventional 12 weeks, which would make it more acceptable and cost effective for patients. A randomised controlled trial of 6 weeks vs 12 weeks of PTNS therapy would be useful in determining the optimal duration of treatment. PMID- 20590545 TI - Phase II study of docetaxel re-treatment in docetaxel-pretreated castration resistant prostate cancer. AB - OBJECTIVE: To determine the activity and tolerability of docetaxel re-treatment after first-line therapy with docetaxel in castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Between November 2005 and January 2009, 45 patients initially responding to docetaxel and then experiencing disease progression after a period of biochemical remission of at least 5 months were enrolled in a prospective multicenter study and re-treated with docetaxel. The primary endpoint was the biochemical response (biochemical partial response defined as > 50% prostate-specific antigen [PSA] decline); secondary endpoints were objective response, toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Partial PSA responses were observed in 11 patients (24.5%), 4 (25%) of whom also had an objective response. The treatment was well tolerated, with grade 1-2 neutropenia, thrombocytopenia, vomiting and peripheral neuropathy noted in 18 (40%), 11 (24.5%), 8 (17.8%), and 6 (13.3%) patients, respectively. The most common grade 3 toxicity was neutropenia, which was observed in 8 patients (17.8%). Median PFS was 5 months and median OS was 13 months. CONCLUSIONS: Docetaxel re-treatment preserves anti-tumour activity and is well tolerated in a selected population of pretreated patients with CRPC. Further randomized trials are needed to confirm our preliminary results. PMID- 20590546 TI - The impact of preoperative erectile dysfunction on survival after radical prostatectomy. AB - PURPOSE: Erectile dysfunction (ED) and cardiovascular disease (CVD) share etiology and pathophysiology. The underlying pathology for preoperative ED may adversely affect survival following radical prostatectomy (RP). We examined the association between preoperative ED and survival following RP. MATERIALS AND METHODS: Between 1983 and 2000, a single surgeon performed RP on 2511 men, with preoperative ED (ED group, n= 231, 9.2%) or without ED (No ED group, n= 2280, 90.8%). We retrospectively analysed their CVD-specific survival (CVDSS), prostate cancer-specific survival (PCSS), non-PCSS (NPCSS) and overall survival (OS) from time of surgery. RESULTS: With median follow-up of 13 years after RP, 449 men (18%) died (140 from prostate cancer, 309 from other causes). Kaplan-Meier analyses demonstrated significant differences in CVDSS (P < 0.001), NPCSS (P < 0.001) and OS (P < 0.001), but not in PCSS (P= 0.12), between the ED group vs No ED group. In univariate proportional hazards analyses, preoperative ED was associated with a significant decrease in OS, hazard ratio (HR), 1.71 (95% CI, 1.34-2.23), P < 0.001. However, in multivariable analyses, the association of ED with survival became non-significant (HR, 1.25 (95% CI, 0.97-1.66), P= 0.111) after adjusting for other prognostic factors, such as age, preoperative prostate specific antigen (PSA) level, Gleason score, pathologic stage, body mass index and Charlson Comorbidity Index. CONCLUSIONS: Preoperative ED is associated with decreased overall survival and survival from causes other than prostate cancer following RP. However, preoperative ED was not an independent predictor of overall survival after adjusting for other predictors of survival. Urologists should carefully assess pretreatment ED status to enhance appropriate treatment recommendation for men with prostate cancer. PMID- 20590547 TI - PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer. AB - OBJECTIVE: To investigate the interaction between, and significance of, ERG gene rearrangements and PTEN genomic deletions in relation to the development and progression of prostate cancer (PCA). PATIENTS AND METHODS: We interrogated an initial cohort of 220 men with localized PCA using fluorescence in situ hybridization for ERG rearrangements and PTEN genomic deletions. RESULTS: The incidences of ERG rearrangements and PTEN deletions in PCA were significantly higher than in high-grade prostatic intra-epithelial neoplasia (HGPIN) and benign prostate tissue (P < 0.001). ERG rearrangements and PTEN deletions were detected in 41.9 and 42.6% of patients' tumours, respectively. ERG rearrangements were never detected in benign prostate tissue, while PTEN aberrations were present at a basal level of 4.6%. PTEN hemizygous deletions showed higher frequency than homozygous deletions within each diagnostic category from benign prostate tissue to HGPIN and PCA (P <= 0.001). Furthermore, in 29 patients where all three tissues were available, PTEN genomic aberrations in PCA were significantly different from those in benign tissue (P = 0.005) and HGPIN (P = 0.02), reflecting the accumulation of genomic aberrations in the early stages of disease progression. Within this cohort, 71.4% of homozygous and 44.2% of hemizygous PTEN deletions occurred simultaneously with ERG rearrangements (P ~ 0). Stratified according to Gleason score (GS), hemizygous PTEN deletions across various GS groups were observed at a higher frequency than homozygous deletions. However, PTEN homozygous deletions showed positive trends with higher GS, increasing in poorly differentiated PCA (GS 8-10) in comparison to moderately and well differentiated tumours (GS 6 and 7). CONCLUSION: We show significant association between ERG gene rearrangements and PTEN genomic aberrations in subset of PCA. Our analysis also provides further support for the observation that homozygous PTEN deletions can occur within the subset of HGPIN lesions, and shows accumulating genetic aberrations with disease progression, evidenced by higher detection in PCA than in HGPIN and more PTEN homozygous deletions in GS 8-10 than in 6-7. PMID- 20590548 TI - The prevalence of chronic constipation and faecal incontinence among men and women with symptoms of overactive bladder. AB - OBJECTIVE: To estimate the prevalence and overlap of overactive bladder (OAB), chronic constipation (CC) and faecal incontinence (FI) among a general population sample of adults in the USA. PATIENTS AND METHODS: A cross-sectional internet based survey of randomly selected panel members who were >= 40 years of age was conducted. Participants reported how often they experienced symptoms of OAB, CC and FI using Likert scales and modified Rome III criteria. Analyses were conducted to examine the overall prevalence of OAB, CC and FI in men and women separately and to characterize the extent of overlap between these conditions in participants with OAB vs those without OAB, and those participants with continent vs incontinent OAB. RESULTS: The response rate for the survey was 62.2% and the final sample (N= 2000) included 927 men and 1073 women. The overall prevalence of OAB [defined as a response of >= 'sometimes' to urinary urgency (i.e. 'sometimes' or more often) or 'yes' to urinary urgency incontinence (UUI)] was 26.1% in men and 41.2% in women. The overall prevalence of CC was significantly lower in men than in women (15.3 vs 26.3%), but both men and women with OAB were significantly more likely to report CC (22.3 and 35.9% vs 5.7 and 6.7%, respectively, P < 0.0001). The overall prevalence of FI reported 'rarely' or more was 16.7% of men and 21.9% of women. Men and women with OAB were significantly more likely to report FI than those without OAB. FI was also more common in participants with incontinent OAB than in those with continent OAB. Logistic regressions controlling for demographic factors and comorbid conditions suggest that OAB status is a very strong predictor of CC, FI and overlapping CC and FI (odds ratios, range 3.55-7.96). CONCLUSIONS: Chronic constipation, FI and overlapping CC and faecal incontinence occur more frequently in patients with OAB and should be considered when evaluating and treating patients with OAB. These findings suggest a shared pathophysiology among these conditions. Additional study is needed to determine if successful treatment of one or more of these conditions is accompanied by commensurate improvement in symptoms referable to the other organ system. PMID- 20590549 TI - Bladder outlet obstruction: progression from inflammation to fibrosis. AB - OBJECTIVE: To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO. MATERIALS AND METHODS: Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor beta (TGF-beta), connective tissue growth factor (CTGF), hypoxia inducible factor 1alpha (HIF-1alpha), and platelet derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for alpha-smooth muscle actin (alpha-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis. RESULTS: After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-beta, CTGF, HIF-1alpha, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for alpha-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks. CONCLUSION: With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation. PMID- 20590550 TI - Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment. AB - OBJECTIVE: To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections. PATIENTS AND METHODS: This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization. Injections were performed using a rigid cystoscope, under local anaesthetic. Patients received BoNT-A as either Botox(r) (Allergan Inc., Irvine, CA, USA) 300 U in 30 sites or Dysport(r) (Ipsen Ltd, Ipsen, Paris, France) 750 U in 20 sites. Urine culture was done 6 days and 6 weeks after the injections. If urinary tract infection (UTI) was suspected, a physician performed a complete physical examination. The primary outcome criterion was the occurrence of UTI during the first week after injections. RESULTS: In all, 42 patients (22 women, 20 men) with a mean (sd) age 45.3 (16.4) years were included. A symptomatic UTI occurred during the first week after the injections in three patients (7.1%). The urinary colonization rate was 31% and 26% at 6 days and 6 weeks after injection, respectively. The most common bacterium was Escherichia coli (62.5%). There were no differences between 20 and 30 injection sites or between the sexes. CONCLUSION: The rate of UTI after intradetrusor injections of BoNT-A was 7.1%. The most frequent bacterium involved was Escherichia coli. These results indicate that antibiotic prophylaxis for intradetrusor BoNT-A injections seems necessary. PMID- 20590551 TI - Coffee consumption and risk of prostate cancer: a meta-analysis of epidemiological studies. AB - OBJECTIVE: To evaluate the association between coffee consumption and the risk of prostate cancer. METHODS: We searched PubMed, EMBASE, and the bibliographies of relevant articles in August 2009. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. RESULTS: Twelve epidemiological studies (eight case-control studies and four cohort studies) were included in the final analysis. In a meta-analysis of all included studies, when compared with the lowest level of coffee consumption, the overall relative risk (RR) of prostate cancer for the highest level of coffee consumption was 1.16 (95% confidence interval [CI] 1.01-1.33). In subgroup meta-analyses by study design, there was a significant positive (harmful) association between coffee consumption and prostate cancer risk in seven case-control studies using both crude and adjusted data (RR 1.20, 95% CI 1.02-1.40; and RR 1.21, 95% CI 1.03-1.43, respectively), whereas there was no significant association in four cohort studies using crude or adjusted data (RR 0.97, 95% CI 0.68-1.38; and RR 1.06, 95% CI 0.83-1.35, respectively). CONCLUSION: Given that a cohort study gives a higher level of evidence than a case-control study, there is no evidence to support a harmful effect of coffee consumption on prostate cancer risk. Further prospective cohort studies are required. PMID- 20590552 TI - Number of prostate cancer risk alleles may identify possibly 'insignificant' disease. AB - OBJECTIVE: To determine whether the cumulative effects of five prostate cancer risk alleles (three single-nucleotide polymorphisms [SNPs] on chromosome 8Q24 and two SNPs on chromosome 17a) could help to identify possibly 'insignificant' disease. MATERIALS AND METHODS: We genotyped 629 men of European ancestry who underwent radical prostatectomy at our institution between 2002 and 2007. Possibly 'insignificant' CaP was defined using the Ohori criteria (organ confined, tumour volume <0.5 mL, Gleason pattern <=4). Statistical analysis was used to compare patients with 'insignificant' and all other 'significant' cancer based upon genotype. Carrier status for the 5 SNPs were compared between patients with 'insignificant' disease and a separate population of 801 controls without CaP. RESULTS: Overall, 38 (6.0%) patients with CaP met the Ohori criteria for 'insignificant' disease. Men with 'significant' cancer had a greater frequency of any of the five risk alleles than either patients with 'insignificant' disease or controls. None of the individual alleles genotyped on chromosomes 8 or 17 distinguished between 'significant' and 'insignificant' CaP. However, carriers of two or more risk alleles were more likely to have 'significant' disease. CONCLUSIONS: Although no single risk allele distinguished 'insignificant' CaP, 'insignificant' disease was nearly three times as likely among carriers of <= one risk allele. Future studies are needed to further elucidate the cumulative relationship between CaP risk alleles and CaP aggressiveness. PMID- 20590553 TI - Pharmacokinetic study to optimize the intravesical administration of gemcitabine. AB - OBJECTIVES: To assess in a phase II pharmacokinetic study whether different pH levels, dilution volumes and exposure times affect intracellular bioavailability and systemic absorption of gemcitabine. SUBJECTS AND METHODS: Six arms of three patients each with a non-muscle-invasive bladder cancer (NMIBC) were planned to receive six combinations of two different dilution volumes (50 mL vs 100 mL), two pH levels (2.5-3.5 vs 5.5) and two exposure times (1 h vs 2 h) of the study drug. Blood samples were taken before, during and 1 h after drug instillation. Cold biopsy specimens from the exophytic tumor, its base of implant and a macroscopically healthy mucosa were taken during transurethral resection. High pressure liquid chromatography/high-resolution mass spectrometry (HPLC/HRMSn) analysis of plasma and tissue samples was used to determine concentrations of gemcitabine (dFdC) and its inactive metabolite (dFdU). RESULTS: The arm at pH 5.5 in 50 mL was withdrawn as 2000 mg dFdC are insoluble in these conditions. The different instillation conditions resulted in negligible plasma dFdC concentrations but significant differences in intracellular content and metabolism of dFdC. The lowest intratissue concentration of dFdC was detected in a 50 mL solution at a pH of 2.5-3.5 kept in the bladder for 1 h (standard arm). A pH 5.5 solution in 100 mL with a 2-h exposure favored the maximal intratumoral dFdC absorption which was 90 times higher than that recorded in the standard arm. CONCLUSIONS: The most commonly reported administration scheme of gemcitabine produced the lowest tissue bioavailability of dFdC. Other combinations of pH, dilution volume and duration of instillation proved more advantageous and merit testing in clinical trials. PMID- 20590554 TI - Themed issue: cannabinoids. PMID- 20590555 TI - Quantification of brain endocannabinoid levels: methods, interpretations and pitfalls. AB - Endocannabinoids play an important role in a diverse range of neurophysiological processes including neural development, neuroimmune function, synaptic plasticity, pain, reward and affective state. This breadth of influence and evidence for altered endocannabinoid signalling in a variety of neuropathologies has fuelled interest in the accurate quantification of these lipids in brain tissue. Established methods for endocannabinoid quantification primarily employ solvent-based lipid extraction with further sample purification by solid phase extraction. In recent years in vivo microdialysis methods have also been developed for endocannabinoid sampling from the brain interstitial space. However, considerable variability in estimates of endocannabinoid content has led to debate regarding the physiological range of concentrations present in various brain regions. This paper provides a critical review of factors that influence the quantification of brain endocannabinoid content as determined by lipid extraction from bulk tissue and by in vivo microdialysis. A variety of methodological issues are discussed including analytical approaches, endocannabinoid extraction and purification, post-mortem changes in brain endocannabinoid content, cellular reactions to microdialysis probe implantation and caveats related to lipid sampling from the extracellular space. The application of these methods for estimating brain endocannabinoid content and the effects of endocannabinoid clearance inhibition are discussed. The benefits, limitations and pitfalls associated with each approach are emphasized, with an eye toward the appropriate interpretation of data gathered by each method. PMID- 20590556 TI - Adenosine-cannabinoid receptor interactions. Implications for striatal function. AB - Adenosine and endocannabinoids are very ubiquitous non-classical neurotransmitters that exert a modulatory role on the transmission of other more 'classical' neurotransmitters. In this review we will focus on their common role as modulators of dopamine and glutamate neurotransmission in the striatum, the main input structure of the basal ganglia. We will pay particular attention to the role of adenosine A(2A) receptors and cannabinoid CB(1) receptors. Experimental results suggest that presynaptic CB(1) receptors interacting with A(2A) receptors in cortico-striatal glutamatergic terminals that make synaptic contact with dynorphinergic medium-sized spiny neurons (MSNs) are involved in the motor-depressant and addictive effects of cannabinoids. On the other hand, postsynaptic CB(1) receptors interacting with A(2A) and D(2) receptors in the dendritic spines of enkephalinergic MSNs and postsynaptic CB(1) receptors in the dendritic spines of dynorphinergic MSN are probably involved in the cataleptogenic effects of cannabinoids. These receptor interactions most probably depend on the existence of a variety of heteromers of A(2A), CB(1) and D(2) receptors in different elements of striatal spine modules. Drugs selective for the different striatal A(2A) and CB(1) receptor heteromers could be used for the treatment of neuropsychiatric disorders and drug addiction and they could provide effective drugs with fewer side effects than currently used drugs. PMID- 20590557 TI - Cannabinoid CB1 receptor-interacting proteins: novel targets for central nervous system drug discovery? AB - The main pharmacological effects of marijuana, as well as synthetic and endogenous cannabinoids, are mediated through G-protein-coupled receptors (GPCRs), including CB(1) and CB(2) receptors. The CB(1) receptor is the major cannabinoid receptor in the central nervous system and has gained increasing interest as a target for drug discovery for treatment of nausea, cachexia, obesity, pain, spasticity, neurodegenerative diseases and mood and substance abuse disorders. Evidence has accumulated to suggest that CB(1) receptors, like other GPCRs, interact with and are regulated by several other proteins beyond the established role of heterotrimeric G-proteins. These proteins, which include the GPCR kinases, beta-arrestins, GPCR-associated sorting proteins, factor associated with neutral sphingomyelinase, other GPCRs (heterodimerization) and the novel cannabinoid receptor-interacting proteins: CRIP(1a/b), are thought to play important roles in the regulation of intracellular trafficking, desensitization, down-regulation, signal transduction and constitutive activity of CB(1) receptors. This review examines CB(1) receptor-interacting proteins, including heterotrimeric G-proteins, but with particular emphasis on non-G-protein entities, that might comprise the CB(1) receptosomal complex. The evidence for direct interaction with CB(1) receptors and potential functional roles of these interacting proteins is discussed, as are future directions and challenges in this field with an emphasis on the possibility of eventually targeting these proteins for drug discovery. PMID- 20590558 TI - CB2: a cannabinoid receptor with an identity crisis. AB - CB(2) was first considered to be the 'peripheral cannabinoid receptor'. This title was bestowed based on its abundant expression in the immune system and presumed absence from the central nervous system. However, multiple recent reports question the absence of CB(2) from the central nervous system. For example, it is now well accepted that CB(2) is expressed in brain microglia during neuroinflammation. However, the extent of CB(2) expression in neurons has remained controversial. There have been studies claiming either extreme-its complete absence to its widespread expression-as well as everything in between. This review will discuss the reported tissue distribution of CB(2) with a focus on CB(2) in neurons, particularly those in the central nervous system as well as the implications of that presence. As CB(2) is an attractive therapeutic target for pain management and immune system modulation without overt psychoactivity, defining the extent of its presence in neurons will have a significant impact on drug discovery. Our recommendation is to encourage cautious interpretation of data that have been presented for and against CB(2)'s presence in neurons and to encourage continued rigorous study. PMID- 20590560 TI - Animal models of cannabinoid reward. AB - The endogenous cannabinoid system is involved in numerous physiological and neuropsychological functions. Medications that target this system hold promise for the treatment of a wide variety of disorders. However, as reward is one of the most prominent of these functions, medications that activate this system must be evaluated for abuse potential. Meanwhile, cannabis is already being used chronically by millions of people, many of whom eventually seek treatment for cannabis dependence. Therefore, there is a need for procedures that can be used to: (i) better understand the mechanisms of cannabinoid reward; (ii) evaluate the abuse potential of new medications; and (iii) evaluate the effectiveness of medications developed for treating cannabis dependence. Animal models of cannabinoid reward provide a means of accomplishing these goals. In this review, we briefly describe and evaluate these models, their advantages and their shortcomings. Special emphasis is placed on intravenous cannabinoid self administration in squirrel monkeys, a valid, reliable and flexible model that we have developed over the past decade. Although the conditions under which cannabinoid drugs have rewarding effects may be more restricted than with other drugs of abuse such as cocaine and heroin, work with these models indicates that cannabinoid reward involves similar brain mechanisms and produces the same kinds of reward-related behaviour. By continuing to use these animal models as tools in the development of new medications, it should be possible to take advantage of the potential benefits provided by the endocannabinoid system while minimizing its potential for harm. PMID- 20590559 TI - The endocannabinoid system as a target for the treatment of neurodegenerative disease. AB - The Cannabis sativa plant has been exploited for medicinal, agricultural and spiritual purposes in diverse cultures over thousands of years. Cannabis has been used recreationally for its psychotropic properties, while effects such as stimulation of appetite, analgesia and anti-emesis have lead to the medicinal application of cannabis. Indeed, reports of medicinal efficacy of cannabis can been traced back as far as 2700 BC, and even at that time reports also suggested a neuroprotective effect of the cultivar. The discovery of the psychoactive component of cannabis resin, Delta(9)-tetrahydrocannabinol (Delta(9)-THC) occurred long before the serendipitous identification of a G-protein coupled receptor at which Delta(9)-THC is active in the brain. The subsequent finding of endogenous cannabinoid compounds, the synthesis of which is directed by neuronal excitability and which in turn served to regulate that excitability, further widened the range of potential drug targets through which the endocannabinoid system can be manipulated. As a result of this, alterations in the endocannabinoid system have been extensively investigated in a range of neurodegenerative disorders. In this review we examine the evidence implicating the endocannabinoid system in the cause, symptomatology or treatment of neurodegenerative disease. We examine data from human patients and compare and contrast this with evidence from animal models of these diseases. On the basis of this evidence we discuss the likely efficacy of endocannabinoid-based therapies in each disease context. PMID- 20590562 TI - Phytocannabinoids beyond the Cannabis plant - do they exist? AB - It is intriguing that during human cultural evolution man has detected plant natural products that appear to target key protein receptors of important physiological systems rather selectively. Plants containing such secondary metabolites usually belong to unique chemotaxa, induce potent pharmacological effects and have typically been used for recreational and medicinal purposes or as poisons. Cannabis sativa L. has a long history as a medicinal plant and was fundamental in the discovery of the endocannabinoid system. The major psychoactive Cannabis constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) potently activates the G-protein-coupled cannabinoid receptor CB(1) and also modulates the cannabinoid receptor CB(2). In the last few years, several other non-cannabinoid plant constituents have been reported to bind to and functionally interact with CB receptors. Moreover, certain plant natural products, from both Cannabis and other plants, also target other proteins of the endocannabinoid system, such as hydrolytic enzymes that control endocannabinoid levels. In this commentary we summarize and critically discuss recent findings. PMID- 20590561 TI - Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models. AB - Cannabis is one of the most widely used illicit drugs among adolescents, and most users first experiment with it in adolescence. Adolescence is a critical phase for brain development, characterized by neuronal maturation and rearrangement processes, such as myelination, synaptic pruning and dendritic plasticity. The endocannabinoid system plays an important role in fundamental brain developmental processes such as neuronal cell proliferation, migration and differentiation. Therefore changes in endocannabinoid activity during this specific developmental phase, induced by the psychoactive component of marijuana, Delta(9) tetrahydrocannabinol, might lead to subtle but lasting neurobiological changes that can affect brain functions and behaviour. In this review, we outline recent research into the endocannabinoid system focusing on the relationships between adolescent exposure to cannabinoids and increased risk for certain neuropsychiatric diseases such as schizophrenia, as highlighted by both human and animal studies. Particular emphasis will be given to the possible mechanisms by which adolescent cannabis consumption could render a person more susceptible to developing psychoses such as schizophrenia. PMID- 20590564 TI - How important are sex differences in cannabinoid action? AB - In humans as in animals, males and females are dissimilar in their genetic and hormonally driven behaviour; they process information differently, perceive experience and emotions in different ways, display diverse attitudes, language and social skills, and show sex-related differences in the brain anatomy and organization. Drug addiction is a widespread relapsing illness that affects both men and women. Sex-dependent differences have been frequently observed in the biological and behavioural effects of substances of abuse, including cannabis. Beside sex differences observed in the cannabinoid-induced effects related to cannabis abuse and dependence, cannabinoids have been shown to exert sex dependent effects also in other physiological and behavioural aspects, such as food intake and energy balance (more evident in males), or anxiety and depression (more evident in females). Research has just begun to identify factors which could provide a neurobiological basis for gender-based differences in cannabinoid effects, among which, gonadal hormones seem to play a crucial role. Yet, cannabinoid pharmacodynamic and pharmacokinetic may also be important, as sex differences in cannabinoid effects might be due, at least in part, to differences in muscle mass and fat tissue distribution between males and females. Here, we will review both clinical and laboratory-based research evidence revealing important sex-related differences in cannabinoid effects, and put forward some suggestions for future studies to fill the gap in our knowledge of gender specific bias in cannabinoid pharmacology. PMID- 20590563 TI - Endocannabinoid signalling: has it got rhythm? AB - Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. The daily and seasonal cycles of the relationship of the earth and sun profoundly affect the terrestrial environment. Terrestrial species have adapted to these cycles in many ways, most well studied are circadian rhythms and hibernation. The purpose of this review was to examine literature support for three hypotheses: (i) endocannabinoid signalling exhibits brain region-specific circadian rhythms; (ii) endocannabinoid signalling modulates the rhythm of circadian processes in mammals; and (iii) changes in endocannabinoid signalling contribute to the state of hibernation. The results of two novel studies are presented. First, we report the results of a study of healthy humans demonstrating that plasma concentrations of the endocannabinoid, N arachidonylethanolamine (anandamide), exhibit a circadian rhythm. Concentrations of anandamide are threefold higher at wakening than immediately before sleep, a relationship that is dysregulated by sleep deprivation. Second, we investigated differences in endocannabinoids and congeners in plasma from Marmota monax obtained in the summer and during the torpor state of hibernation. We report that 2-arachidonoylglycerol is below detection in M. monax plasma and that concentrations of anandamide are not different. However, plasma concentrations of the anorexigenic lipid oleoylethanolamide were significantly lower in hibernation, while the concentrations of palmitoylethanolamide and 2 oleoylglycerol were significantly greater in hibernation. We conclude that available data support a bidirectional relationship between endocannabinoid signalling and circadian processes, and investigation of the contribution of endocannabinoid signalling to the dramatic physiological changes that occur during hibernation is warranted. PMID- 20590566 TI - Evidence for both inverse agonism at the cannabinoid CB1 receptor and the lack of an endogenous cannabinoid tone in the rat and guinea-pig isolated ileum myenteric plexus-longitudinal muscle preparation. AB - BACKGROUND AND PURPOSE: Cannabinoid receptor agonists reduce intestinal propulsion in rodents through the CB(1) receptor. In addition to its antagonistic activity at this receptor, rimonabant (N-(piperidino)-5-(4-chlorophenyl)-1-(2,4 dichlorophenyl)-4-methyl-3-pyrazole-carboxyamide) alone augments intestinal transit. Using rat and guinea-pig ileum MPLM (myenteric plexus-longitudinal muscle) preparations, we investigated whether the latter effect was through inverse agonism or antagonism of endocannabinoid agonist(s). EXPERIMENTAL APPROACH: Inverse agonism was investigated by comparing the maximal enhancement of electrically evoked contractions of the MPLM by two CB(1) receptor antagonists, AM 251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4 methyl-1H-pyrazole-3-carboxamide) and O-2050 [(6aR,10aR)-3-(1 methanesulphonylamino-4-hexyn-6-yl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6-H dibenzo[b,d]pyran], with that produced by rimonabant. To reveal ongoing endocannabinoid activity, effects of inhibiting endocannabinoid hydrolysis by fatty acid amide hydrolase (FAAH) using AA-5HT (arachidonyl-5-hydroxytryptamine), PMSF (phenylmethylsulphonyl fluoride) or URB-597 (3'-carbamoyl-biphenyl-3-yl cyclohexylcarbamate), or putative uptake using VDM-11 [(5Z,8Z,11Z,14Z)-N-(4 hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide] was evaluated. KEY RESULTS: The presence of CB(1) receptors was revealed by antagonism of exogenous anandamide, arachidonylethanolamide (AEA) and WIN 55,212-2 [(R)-(+)-[2,3-dihydro 5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1 naphthalenylmethanone mesylate] by rimonabant. The rank order of potentiation of contractions was AM 251 > rimonabant > O-2050. Neither the FAAH inhibitors nor VDM-11 affected electrically evoked contractions. Each FAAH inhibitor increased the potency of AEA but not WIN 55,212-2. VDM-11 did not alter the inhibitory effect of AEA. CONCLUSIONS AND IMPLICATIONS: The different levels of maximal potentiation of contractions by the CB(1) receptor antagonists suggest inverse agonism. The potentiation of the action of AEA by the FAAH inhibitors showed that FAAH was present. The lack of effect of FAAH inhibitors and VDM-11 alone on electrically evoked contractions, and on the potency of exogenous AEA suggests that pharmacologically active endocannabinoids were not released and the endocannabinoid transporter was absent. Thus, the CB(1) receptor antagonists behave as inverse agonists. PMID- 20590565 TI - Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase. AB - BACKGROUND AND PURPOSE: Inhibitors of fatty acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of the endogenous cannabinoid (CB) receptor ligand anandamide (AEA), are effective in a number of animal models of pain. Here, we investigated a series of isoflavones with respect to their abilities to inhibit FAAH. EXPERIMENTAL APPROACH: In vitro assays of FAAH activity and affinity for CB receptors were used to characterize key compounds. In vivo assays used were biochemical responses to formalin in anaesthetized mice and the 'tetrad' test for central CB receptor activation. KEY RESULTS: Of the compounds tested, biochanin A was adjudged to be the most promising. Biochanin A inhibited the hydrolysis of 0.5 microM AEA by mouse, rat and human FAAH with IC(50) values of 1.8, 1.4 and 2.4 microM respectively. The compound did not interact to any major extent with CB(1) or CB(2) receptors, nor with FAAH-2. In anaesthetized mice, URB597 (30 microg i.pl.) and biochanin A (100 microg i.pl.) both inhibited the spinal phosphorylation of extracellular signal-regulated kinase produced by the intraplantar injection of formalin. The effects of both compounds were significantly reduced by the CB(1) receptor antagonist/inverse agonist AM251 (30 microg i.pl.). Biochanin A (15 mg.kg(-1) i.v.) did not increase brain AEA concentrations, but produced a modest potentiation of the effects of 10 mg.kg(-1) i.v. AEA in the tetrad test. CONCLUSIONS AND IMPLICATIONS: It is concluded that biochanin A, in addition to its other biochemical properties, inhibits FAAH both in vitro and peripherally in vivo. PMID- 20590567 TI - Physical and functional interaction between CB1 cannabinoid receptors and beta2 adrenoceptors. AB - BACKGROUND AND PURPOSE: The CB(1) cannabinoid receptor and the beta(2) adrenoceptor are G protein-coupled receptors (GPCRs) co-expressed in many tissues. The present study examined physical and functional interactions between these receptors in a heterologous expression system and in primary human ocular cells. EXPERIMENTAL APPROACH: Physical interactions between CB(1) receptors and beta(2)-adrenoceptors were assessed using bioluminescence resonance energy transfer (BRET). Functional interactions between these receptors were evaluated by examining receptor trafficking, as well as extracellular signal-regulated kinase (ERK) and cyclic AMP response element binding protein (CREB) signalling. KEY RESULTS: Physical interactions between CB(1) receptors and beta(2) adrenoceptors were demonstrated using BRET. In human embryonic kidney (HEK) 293H cells, co-expression of beta(2)-adrenoceptors tempered the constitutive activity and increased cell surface expression of CB(1) receptors. Co-expression altered the signalling properties of CB(1 )receptors, resulting in increased Galpha(i) dependent ERK phosphorylation, but decreased non-Galpha(i)-mediated CREB phosphorylation. The CB(1) receptor inverse agonist AM251 (N-(piperidin-1-yl)-5 (4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) attenuated beta(2)-adrenoceptor-pERK signalling in cells expressing both receptors, while the CB(1) receptor neutral antagonist O-2050 ((6aR,10aR)-3-(1 methanesulfonylamino-4-hexyn-6-yl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H dibenzo[b,d]pyran) did not. The actions of AM251 and O-2050 were further examined in primary human trabecular meshwork (HTM) cells, which are ocular cells endogenously co-expressing CB(1) receptors and beta(2)-adrenoceptors. In HTM cells, as in HEK 293H cells, AM251 but not O-2050, altered the beta(2) adrenoceptor-pERK response. CONCLUSION AND IMPLICATIONS: A complex interaction was demonstrated between CB(1) receptors and beta(2)-adrenoceptors in HEK 293H cells. As similar functional interactions were also observed in HTM cells, such interactions may affect the pharmacology of these receptors in tissues where they are endogenously co-expressed. PMID- 20590568 TI - Regulation of Fas receptor/Fas-associated protein with death domain apoptotic complex and associated signalling systems by cannabinoid receptors in the mouse brain. AB - BACKGROUND AND PURPOSE: Natural and synthetic cannabinoids (CBs) induce deleterious or beneficial actions on neuronal survival. The Fas-associated protein with death domain (FADD) promotes apoptosis, and its phosphorylated form (p-FADD) mediates non-apoptotic actions. The regulation of Fas/FADD, mitochondrial apoptotic proteins and other pathways by CB receptors was investigated in the mouse brain. EXPERIMENTAL APPROACH: Wild-type, CB(1) and CB(2) receptor knock-out (KO) mice were used to assess differences in receptor genotypes. CD1 mice were used to evaluate the effects of CB drugs on canonical apoptotic pathways and associated signalling systems. Target proteins were quantified by Western blot analysis. KEY RESULTS: In brain regions of CB(1) receptor KO mice, Fas/FADD was reduced, but p-Ser191 FADD and the p-FADD/FADD ratio were increased. In CB(2) receptor KO mice, Fas/FADD was increased, but the p-FADD/FADD ratio was not modified. In mutant mice, cleavage of poly(ADP-ribose) polymerase (PARP) did not indicate alterations in brain cell death. In CD1 mice, acute WIN55212-2 (CB(1) receptor agonist), but not JWH133 (CB(2) receptor agonist), inversely modulated brain FADD and p-FADD. Chronic WIN55212-2 induced FADD down-regulation and p-FADD up-regulation. Acute and chronic WIN55212-2 did not alter mitochondrial proteins or PARP cleavage. Acute, but not chronic, WIN55212-2 stimulated activation of anti-apoptotic (ERK, Akt) and pro-apoptotic (JNK, p38 kinase) pathways. CONCLUSIONS AND IMPLICATIONS: CB(1) receptors appear to exert a modest tonic activation of Fas/FADD complexes in brain. However, chronic CB(1) receptor stimulation decreased pro-apoptotic FADD and increased non apoptotic p-FADD. The multifunctional protein FADD could participate in the mechanisms of neuroprotection induced by CBs. PMID- 20590570 TI - Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids. AB - BACKGROUND AND PURPOSE: Recent studies suggest that the effects of cyclooxygenase 2 (COX-2) inhibition are mediated by cannabinoid receptor activation. However, some non-steroidal anti-inflammatory drugs inhibit the enzyme fatty acid amide hydrolase, which regulates levels of some endocannabinoids. Whether COX-2 directly regulates levels of endocannabinoids in vivo is unclear. Here, the effect of the COX-2 inhibitor nimesulide, which does not inhibit fatty acid amide hydrolase, on spinal nociceptive processing was determined. Effects of nimesulide on tissue levels of endocannabinoids and related compounds were measured and the role of cannabinoid 1 (CB(1)) receptors was determined. EXPERIMENTAL APPROACH: Effects of spinal and peripheral administration of nimesulide (1-100 microg per 50 microL) on mechanically evoked responses of rat dorsal horn neurones were measured, and the contribution of the CB(1) receptor was determined with the antagonist AM251 (N-(piperidin-1-yl)-5-(-4-iodophenyl)-1-(2,4-dichlorophenyl)-4 methyl-1H-pyrazole-3-carboxamide), in anaesthetized rats. Effects of nimesulide on spinal levels of endocannabinoids and related compounds were quantified using liquid chromatography-tandem mass spectrometry. KEY RESULTS: Spinal, but not peripheral, injection of nimesulide (1-100 microg per 50 microL) significantly reduced mechanically evoked responses of dorsal horn neurones. Inhibitory effects of spinal nimesulide were blocked by the CB(1) receptor antagonist AM251 (1 microg per 50 microL), but spinal levels of endocannabinoids were not elevated. Indeed, both anandamide and N-oleoylethanolamide (OEA) were significantly decreased by nimesulide. CONCLUSIONS AND IMPLICATIONS: Although the inhibitory effects of COX-2 blockade on spinal neuronal responses by nimesulide were dependent on CB(1) receptors, we did not detect a concomitant elevation in anandamide or 2-AG. Further understanding of the complexities of endocannabinoid catabolism by multiple enzymes is essential to understand their contribution to COX-2-mediated analgesia. PMID- 20590569 TI - CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. AB - BACKGROUND AND PURPOSE: Accumulating recent evidence suggests that cannabinoid-1 (CB(1)) receptor activation may promote inflammation and cell death and its pharmacological inhibition is associated with anti-inflammatory and tissue protective effects in various preclinical disease models, as well as in humans. EXPERIMENTAL APPROACH: In this study, using molecular biology and biochemistry methods, we have investigated the effects of genetic deletion or pharmacological inhibition of CB(1) receptors on inflammation, oxidative/nitrosative stress and cell death pathways associated with a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. RESULTS: Cisplatin significantly increased endocannabinoid anandamide content, activation of p38 and JNK mitogen-activated protein kinases (MAPKs), apoptotic and poly (ADP ribose)polymerase-dependent cell death, enhanced inflammation (leucocyte infiltration, tumour necrosis factor-alpha and interleukin-1beta) and promoted oxidative/nitrosative stress [increased expressions of superoxide-generating enzymes (NOX2(gp91phox), NOX4), inducible nitric oxide synthase and tissue 4 hydroxynonenal and nitrotyrosine levels] in the kidneys of mice, accompanied by marked histopathological damage and impaired renal function (elevated creatinine and serum blood urea nitrogen) 3 days following its administration. Both genetic deletion and pharmacological inhibition of CB(1) receptors with AM281 or SR141716 markedly attenuated the cisplatin-induced renal dysfunction and interrelated oxidative/nitrosative stress, p38 and JNK MAPK activation, cell death and inflammatory response in the kidney. CONCLUSIONS AND IMPLICATIONS: The endocannabinoid system through CB(1) receptors promotes cisplatin-induced tissue injury by amplifying MAPK activation, cell death and interrelated inflammation and oxidative/nitrosative stress. These results also suggest that inhibition of CB(1) receptors may exert beneficial effects in renal (and most likely other) diseases associated with enhanced inflammation, oxidative/nitrosative stress and cell death. PMID- 20590571 TI - The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. AB - BACKGROUND AND PURPOSE: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors. This investigation explored its ability to activate CB(2) receptors, there being evidence that combined CB(2) activation/CB(1) blockade would ameliorate certain disorders. EXPERIMENTAL APPROACH: We tested the ability of THCV to activate CB(2) receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB(2) (hCB(2)) receptors; (ii) it stimulated [(35)S]GTPgammaS binding to hCB(2) CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB(1) or CB(2) receptor antagonist. KEY RESULTS: THCV inhibited cyclic AMP production by hCB(2) CHO cells (EC(50)= 38 nM), but not by hCB(1) or untransfected CHO cells or by hCB(2) CHO cells pre-incubated with pertussis toxin (100 ng.mL(-1)) and stimulated [(35)S]GTPgammaS binding to hCB(2) CHO and mouse spleen membranes. THCV (0.3 or 1 mg.kg(-1) i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB(2) receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg.kg(-1), and in both phases of this test at 5 mg.kg(-1); these effects of THCV appeared to be CB(1) and CB(2) receptor mediated. CONCLUSIONS AND IMPLICATIONS: THCV can activate CB(2) receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB(1) and/or CB(2) receptor activation. PMID- 20590572 TI - Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. AB - BACKGROUND AND PURPOSE: Impaired endothelial activity and/or cell death play a critical role in the development of vascular dysfunction associated with congestive heart failure, diabetic complications, hypertension, coronary artery disease and atherosclerosis. Increasing evidence suggests that cannabinoid 1 (CB(1)) receptor inhibition is beneficial in atherosclerosis and cardiovascular inflammation both in experimental models, as well as in humans. Here, we investigated the effects of CB(1) receptor activation with the endocannabinoid anandamide (AEA) or synthetic agonist HU210 on cell death and interrelated signal transduction pathways in human primary coronary artery endothelial cells (HCAECs). EXPERIMENTAL APPROACH: Cell death, CB(1) receptor expression, reactive oxygen species (ROS) generation and activation of signal transduction pathways in HCAECs were determined by flow cytometry and molecular biology tools. KEY RESULTS: In HCAECs expressing CB(1) receptors (demonstrated by Western immunoblot and flow cytometry) AEA (5-15 microM) or HU210 (30-1000 nM) triggered concentration- and time-dependent activation of p38 and c-Jun NH(2)-terminal protein kinase (JNK)-mitogen-activated protein kinases (MAPKs), cell death and ROS generation. The AEA- or HU210-induced cell death and MAPK activation were attenuated by CB(1) antagonists [SR141716 (rimonabant) and AM281], inhibitors of p38 and JNK-MAPKs or the antioxidant N-acetylcysteine. N-acetylcysteine alone prevented AEA- or HU210-induced ROS generation, but only partially attenuated MAPK activation and cell death. In contrast, in combination with CB(1) antagonists, N-acetylcysteine completely prevented these effects. CONCLUSIONS AND IMPLICATIONS: CB(1) receptor activation in endothelial cells may amplify the ROS MAPK activation-cell death pathway in pathological conditions when the endocannabinoid synthetic or metabolic pathways are dysregulated by excessive inflammation and/or oxidative/nitrosative stress, thereby contributing to the development of endothelial dysfunction and pathophysiology of multiple cardiovascular diseases. PMID- 20590573 TI - Vasorelaxation to N-oleoylethanolamine in rat isolated arteries: mechanisms of action and modulation via cyclooxygenase activity. AB - BACKGROUND AND PURPOSE: The endocannabinoid-like molecule N-oleoylethanolamine (OEA) is found in the small intestine and regulates food intake and promotes weight loss. The principal aim of the present study was to evaluate the vascular effects of OEA. EXPERIMENTAL APPROACH: Perfused isolated mesenteric arterial beds were pre-contracted with methoxamine or high potassium buffers and concentration response curves to OEA were constructed. Combinations of inhibitors to block nitric oxide production, sensory nerve activity, cyclooxygenase activity, potassium channels, chloride channels and gap junctions, and a cannabinoid CB(1) receptor antagonist, were used during these experiments. The effects of OEA on caffeine-induced contractions in calcium-free buffer were also assessed. Isolated thoracic aortic rings were used as a comparison. KEY RESULTS: OEA caused concentration-dependent vasorelaxation in rat isolated mesenteric arterial beds and thoracic aortic rings, with a greater maximal response in mesenteric vessels. This relaxation was sensitive to inhibition of sensory nerve activity and endothelial removal in both preparations. The cyclooxygenase inhibitor indomethacin reversed the effects of capsaicin pre-treatment in perfused mesenteric arterial beds and indomethacin alone enhanced vasorelaxation to OEA. The OEA-induced vasorelaxation was inhibited by a CB(1) receptor antagonist only in aortic rings. In mesenteric arteries, OEA suppressed caffeine-induced contractions in calcium-free buffer. CONCLUSIONS AND IMPLICATIONS: The vasorelaxant effects of OEA are partly dependent on sensory nerve activity and a functional endothelium in the vasculature. In addition, vasorelaxation to OEA is enhanced following cyclooxygenase inhibition. OEA may also interfere with the release of intracellular calcium in arterial preparations. PMID- 20590574 TI - The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. AB - BACKGROUND AND PURPOSE: Cannabis is taken as self-medication by patients with inflammatory bowel disease for symptomatic relief. Cannabinoid receptor agonists decrease inflammation in animal models of colitis, but their effects on the disturbed motility is not known. (-)-Cannabidiol (CBD) has been shown to interact with Delta(9)-tetrahydrocannabinol (THC) in behavioural studies, but it remains to be established if these cannabinoids interact in vivo in inflammatory disorders. Therefore the effects of CBD and THC alone and in combination were investigated in a model of colitis. EXPERIMENTAL APPROACH: The 2,4,6 trinitrobenzene sulphonic acid (TNBS) model of acute colitis in rats was used to assess damage, inflammation (myeloperoxidase activity) and in vitro colonic motility. Sulphasalazine was used as an active control drug. KEY RESULTS: Sulphasalazine, THC and CBD proved beneficial in this model of colitis with the dose-response relationship for the phytocannabinoids showing a bell-shaped pattern on the majority of parameters (optimal THC and CBD dose, 10 mg.kg(-1)). THC was the most effective drug. The effects of these phytocannabinoids were additive, and CBD increased some effects of an ineffective THC dose to the level of an effective one. THC alone and in combination with CBD protected cholinergic nerves whereas sulphasalazine did not. CONCLUSIONS AND IMPLICATIONS: In this model of colitis, THC and CBD not only reduced inflammation but also lowered the occurrence of functional disturbances. Moreover the combination of CBD and THC could be beneficial therapeutically, via additive or potentiating effects. PMID- 20590575 TI - Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones. AB - BACKGROUND AND PURPOSE: Animal and human studies have shown that sex and hormones are key factors in modulating addiction. Previously, we have demonstrated that self-administration of the cannabinoid CB(1) receptor agonist WIN55,212-2 (WIN; 12.5 microg.kg(-1) per infusion) is dependent on sex, intact female rats being more sensitive than males to the reinforcing properties of cannabinoids, and on the oestrous cycle, ovariectomized (OVX) females being less responsive than intact females. EXPERIMENTAL APPROACH: This follow-up study investigated whether sex and ovarian function also affect reinstatement of cannabinoid-seeking in rats after exposure to drug or cue priming. KEY RESULTS: After priming with 0.15 or 0.3 mg.kg(-1) WIN, intact female rats exhibited stronger reinstatement than males and OVX females. Responses of intact female rats were higher than those of male and OVX rats even after priming with a drug-associated visual (Light) or auditory (Tone) cue, or a WIN + Light combination. However, latency to the first response did not differ between intact and OVX female rats, and males showed the longest latency to initiate lever-pressing activity. CONCLUSIONS AND IMPLICATIONS: Our study provides compelling evidence for a pivotal role of sex and the oestrous cycle in modulating cannabinoid-seeking, with ovariectomy diminishing drug and cue-induced reinstatement. However, it is possible that sex differences during self-administration training are responsible for sex differences in reinstatement. Finding that not only drug primings but also acute exposure to drug-associated cues can reinstate responding in rats could have significant implications for the development of pharmacological and behavioural treatments of abstinent female and male marijuana smokers. PMID- 20590576 TI - Endocannabinoid modulation of hyperaemia evoked by physiologically relevant stimuli in the rat primary somatosensory cortex. AB - BACKGROUND AND PURPOSE: In vitro studies demonstrate that cannabinoid CB(1) receptors subserve activity-dependent suppression of inhibition in the neocortex. To examine this mechanism in vivo, we assessed the effects of local changes in CB(1) receptor activity on somatosensory cortex neuronal activation by whisker movement in rats. EXPERIMENTAL APPROACH: Laser Doppler flowmetry and c-Fos immunohistochemistry were used to measure changes in local blood flow and neuronal activation, respectively. All drugs were applied directly to the cranium above the whisker barrel fields of the primary somatosensory cortex. KEY RESULTS: The CB(1) receptor agonist WIN55212-2 potentiated the hyperaemia induced by whisker movement and this potentiation was occluded by bicuculline. The CB(1) receptor antagonists, rimonabant and AM251, inhibited hyperaemic responses to whisker movement; indicating that activation of endogenous CB(1) receptors increased during whisker movement. Whisker movement-induced expression of c-Fos protein in neurons of the whisker barrel cortex was inhibited by rimonabant. Movement of the whiskers increased the 2-arachidonoylglycerol content in the contralateral, compared to the ipsilateral, sensory cortex. CONCLUSIONS AND IMPLICATIONS: These results support the hypothesis that endocannabinoid signalling is recruited during physiologically relevant activation of the sensory cortex. These data support the hypothesis that the primary effect of CB(1) receptor activation within the activated whisker barrel cortex is to inhibit GABA release, resulting in disinhibition of neuronal activation. These studies provide physiological data involving endocannabinoid signalling in activity-dependent regulation of neuronal activation and provide a mechanistic basis for the effects of cannabis use on sensory processing in humans. PMID- 20590577 TI - Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington's disease. AB - BACKGROUND AND PURPOSE: The therapeutic potential of cannabinoids in Huntington's disease (HD) has been investigated by several groups with complex and sometimes contrasting results. We sought to examine key points of intersection between cannabinoid receptor 1 (CB(1)) signalling, survival and the formation of mutant huntingtin aggregates in HD. EXPERIMENTAL APPROACH: Using a simplified pheochromocytoma (PC12) cell model of HD expressing exon 1 of wild-type or mutant huntingtin, we assayed cell death and aggregate formation using high-throughput cytotoxicity and image-based assays respectively. KEY RESULTS: CB(1) activation by HU210 conferred a small but significant level of protection against mutant huntingtin-induced cell death. Pertussis toxin uncoupled HU210 from the inhibition of cAMP, preventing rescue of cell death. Phosphorylation of extracellular signal-regulated kinase (ERK) was also critical to CB(1)-mediated rescue. Conversely, treatments that elevated cAMP exacerbated mutant huntingtin induced cell death. Despite opposing effects on HD cell survival, both HU210 and compounds that elevated cAMP increased the formation of mutant huntingtin aggregates. The increase in aggregation by HU210 was insensitive to Pertussis toxin and UO126, suggesting a G-protein alpha subtype s (G(s))-linked mechanism. CONCLUSIONS AND IMPLICATIONS: We suggest that the CB(1) receptor, through G protein alpha subtype i/o (G(i/o))-linked, ERK-dependent signal transduction, is a therapeutic target in HD. However the protective potential of CB(1) may be limited by promiscuous coupling to G(s), the stimulation of cAMP formation and increased aggregate formation. This may underpin the poor therapeutic efficacy of cannabinoids in more complex model systems and suggest that therapies that are selective for the G(i/o), ERK pathway may be of most benefit in HD. PMID- 20590578 TI - A role for L-alpha-lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells. AB - BACKGROUND AND PURPOSE: Increased circulating levels of L-alpha lysophosphatidylinositol (LPI) are associated with cancer and LPI is a potent, ligand for the G-protein-coupled receptor GPR55. Here we have assessed the modulation of breast cancer cell migration, orientation and polarization by LPI and GPR55. EXPERIMENTAL APPROACH: Quantitative RT-PCR was used to measure GPR55 expression in breast cancer cell lines. Cell migration and invasion were measured using a Boyden chamber chemotaxis assay and Cultrex invasion assay, respectively. Cell polarization and orientation in response to the microenvironment were measured using slides containing nanometric grooves. KEY RESULTS: GPR55 expression was detected in the highly metastatic MDA-MB-231 breast cancer cell line. In these cells, LPI stimulated binding of [(35)S]GTPgammaS to cell membranes (pEC(50) 6.47 +/- 0.45) and significantly enhanced cell chemotaxis towards serum. MCF-7 cells expressed low levels of GPR55 and did not migrate or invade towards serum factors. When GPR55 was over-expressed in MCF-7 cells, serum induced a robust migratory and invasive response, which was further enhanced by LPI and prevented by siRNA to GPR55. The physical microenvironment has been identified as a key factor in determining breast tumour cell metastatic fate. LPI endowed MDA-MB-231 cells with the capacity to detect shallow (40 nm deep) grooved slides and induced marked cancer cell polarization on both flat and grooved surfaces. CONCLUSIONS AND IMPLICATIONS: LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment. PMID- 20590579 TI - Involvement of 2-arachidonoyl glycerol in the increased consumption of and preference for ethanol of mice treated with neurotoxic doses of methamphetamine. AB - BACKGROUND AND PURPOSE: Methamphetamine (METH) is a psychostimulant amphetamine that causes long-term dopaminergic neurotoxicity in mice. Hypodopaminergic states have been demonstrated to increase voluntary ethanol (EtOH) consumption and preference. In addition, the endocannabinoid system has been demonstrated to modulate EtOH drinking behaviour. Thus, we investigated EtOH consumption in METH lesioned animals and the role of cannabinoid (CB) signalling in this EtOH drinking. EXPERIMENTAL APPROACH: Mice were treated with a neurotoxic regimen of METH, and 7 days later exposed to increasing concentrations of drinking solutions of EtOH (3, 6, 10 and 20%). Seven days after neurotoxic METH, the following biochemical determinations were carried out in limbic forebrain: CB(1) receptor density and stimulated activity, 2-arachidonoyl glycerol (2-AG) and monoacylglycerol lipase (MAGL) activity, dopamine levels and dopamine transporter density. KEY RESULTS: EtOH consumption and preference were increased in METH treated mice. Seven days after METH, a time at which both dopamine levels and density of dopamine transporters in limbic forebrain were decreased, CB(1) receptor density and activity were unaltered, but 2-AG levels were increased. At this same time-point, MAGL activity was reduced. The CB(1) receptor antagonist AM251 prevented the METH-induced increase in EtOH consumption and preference, while N-arachidonoyl maleimide, an inhibitor of MAGL, increased EtOH consumption and preference in both saline- and METH-treated mice. CONCLUSIONS AND IMPLICATIONS: An increase in endocannabinoid tone may be involved in the increased consumption of and preference for EtOH displayed by METH-lesioned mice as blockade of the CB(1) receptor decreased EtOH-seeking behaviours, whereas the MAGL inhibitor increased EtOH consumption. PMID- 20590580 TI - Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents. AB - Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Among psoriatic patients, 5-40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of life. Traditional systemic therapies for psoriasis, such as methotrexate, cyclosporin A, retinoids or PUVA therapy, have a potential for long term toxicity and may not always provide sufficient improvement of the disease. The development of novel therapies targeting key steps in the pathogenesis of psoriasis and psoriatic arthritis now provide new and efficient treatment options. Biological therapies for the treatment of psoriasis and/or psoriatic arthritis are defined by their mode of action and can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of tumour necrosis factor-alpha (TNFalpha blockers, e.g. adalimumab, certolizumab, etanercept, golimumab and infliximab) and the inhibitors of interleukin (IL) 12 and IL-23 (e.g. ustekinumab and briakinumab). This article provides a brief overview of the currently approved biological agents in the European Union and of some newer agents, such as briakinumab, certolizumab and golimumab. PMID- 20590581 TI - The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets. AB - GRK2 is a ubiquitous member of the G protein-coupled receptor kinase (GRK) family that appears to play a central, integrative role in signal transduction cascades. GRKs participate together with arrestins in the regulation of G protein-coupled receptors (GPCR), a family of hundreds of membrane proteins of key physiological and pharmacological importance, by triggering receptor desensitization from G proteins and GPCR internalization, and also by helping assemble macromolecular signalosomes in the receptor environment acting as agonist-regulated adaptor scaffolds, thus contributing to signal propagation. In addition, emerging evidence indicates that GRK2 can phosphorylate a growing number of non-GPCR substrates and associate with a variety of proteins related to signal transduction, thus suggesting that this kinase could also have diverse 'effector' functions. We discuss herein the increasing complexity of such GRK2 'interactome', with emphasis on the recently reported roles of this kinase in cell migration and cell cycle progression and on the functional impact of the altered GRK2 levels observed in several relevant cardiovascular, inflammatory or tumour pathologies. Deciphering how the different networks of potential GRK2 functional interactions are orchestrated in a stimulus, cell type or context specific way is critical to unveil the contribution of GRK2 to basic cellular processes, to understand how alterations in GRK2 levels or functionality may participate in the onset or development of several cardiovascular, tumour or inflammatory diseases, and to assess the feasibility of new therapeutic strategies based on the modulation of the activity, levels or specific interactions of GRK2. PMID- 20590582 TI - Compromised vascular endothelial cell SK(Ca) activity: a fundamental aspect of hypertension? AB - Smooth muscle hyperpolarization originating in the endothelium and commonly referred to as the EDHF (endothelium-derived hyperpolarizing factor) response provides a very significant drive to vasodilatation particularly in small resistance arteries. Together with other endothelium-dependent dilator pathways 'EDHF' hyperpolarization is compromised by cardiovascular disease, including hypertension. However, although attenuated vascular hyperpolarization has been described in animal models of hypertension, the underlying mechanisms are not fully understood. In the current issue of the British Journal of Pharmacology, Weston et al. combine classic pharmacological approaches with electrophysiological and molecular techniques to suggest that attenuated endothelium-dependent hyperpolarization (and as a consequence vasodilatation) reflects major disruption of pathways associated with the activation of endothelial small conductance Ca(2+)-activated K-channels (SK(Ca)) in mesenteric arteries from spontaneously hypertensive rats. In addition to reductions in SK(Ca) and K(IR) proteins, changes in caveolin-1 isomers were also detected, possibly indicating channel realignment within plasmalemmal structures. PMID- 20590583 TI - Prostaglandin signalling in cerebral ischaemia. AB - The inducible cyclooxygenase COX-2 exerts neurotoxic effects in a wide spectrum of neurological disease models, including models of cerebral ischaemia and chronic neurodegeneration. As COX-1 and COX-2 catalyse the first committed step in prostaglandin synthesis, recent efforts have focused on identifying the downstream prostaglandin signalling pathways responsible for mediating the toxic effect of COX-2. Recent studies in models of in vitro excitotoxicity or hypoxia demonstrate that certain prostaglandin receptors mediate toxic effects, but a large number appear to mediate paradoxically protective effects. In vivo studies have begun to confirm initial in vitro findings, with selected prostaglandin receptors eliciting either neurotoxic or protective effects in models of cerebral ischaemia. In the present issue, Ikeda-Matsuo et al. examine the function of the PGE(2) EP3 receptor in a model of transient focal ischaemia and explore its potential signalling through Rho kinase activation. PMID- 20590584 TI - Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E2 EP3 receptors. AB - BACKGROUND AND PURPOSE: Although microsomal prostaglandin E synthase (mPGES)-1 is known to contribute to stroke injury, the underlying mechanisms remain poorly understood. This study examines the hypothesis that EP(3) receptors contribute to stroke injury as downstream effectors of mPGES-1 neurotoxicity through Rho kinase activation. EXPERIMENTAL APPROACH: We used a glutamate-induced excitotoxicity model in cultured rat and mouse hippocampal slices and a mouse middle cerebral artery occlusion-reperfusion model. Effects of an EP(3) receptor antagonist on neuronal damage in mPGES-1 knockout (KO) mice was compared with that in wild-type (WT) mice. KEY RESULTS: In cultures of rat hippocampal slices, the mRNAs of EP(1 4) receptors were constitutively expressed and only the EP(3) receptor antagonist ONO-AE3-240 attenuated and only the EP(3) receptor agonist ONO-AE-248 augmented glutamate-induced excitotoxicity in CA1 neurons. Hippocampal slices from mPGES-1 KO mice showed less excitotoxicity than those from WT mice and the EP(3) receptor antagonist did not attenuate the excitotoxicity. In transient focal ischaemia models, injection (i.p.) of an EP(3) antagonist reduced infarction, oedema and neurological dysfunction in WT mice, but not in mPGES-1 KO mice, which showed less injury than WT mice. EP(3) receptor agonist-induced augmentation of excitotoxicity in vitro was ameliorated by the Rho kinase inhibitor Y-27632 and Pertussis toxin. The Rho kinase inhibitor HA-1077 also ameliorated stroke injury in vivo. CONCLUSION AND IMPLICATIONS: Activity of mPGES-1 exacerbated stroke injury through EP(3) receptors and activation of Rho kinase and/or G(i). Thus, mPGES-1 and EP(3) receptors may be valuable therapeutic targets for treatment of human stroke. PMID- 20590585 TI - Mechanisms mediating the ability of caffeine to influence MDMA ('Ecstasy') induced hyperthermia in rats. AB - BACKGROUND AND PURPOSE: Caffeine exacerbates the hyperthermia associated with an acute exposure to 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') in rats. The present study investigated the mechanisms mediating this interaction. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were treated with caffeine (10 mg x kg(-1); i.p.) and MDMA (15 mg x kg(-1); i.p.) alone and in combination. Core body temperatures were monitored before and after drug administration. KEY RESULTS: Central catecholamine depletion blocked MDMA-induced hyperthermia and its exacerbation by caffeine. Caffeine provoked a hyperthermic response when the catecholamine releaser d-amphetamine (1 mg x kg(-1)) was combined with the 5-HT releaser D-fenfluramine (5 mg x kg(-1)) or the non-selective dopamine receptor agonist apomorphine (1 mg x kg(-1)) was combined with the 5-HT(2) receptor agonist DOI (2 mg x kg(-1)) but not following either agents alone. Pretreatment with the dopamine D(1) receptor antagonist Schering (SCH) 23390 (1 mg x kg(-1)), the 5-HT(2) receptor antagonist ketanserin (5 mg x kg(-1)) or alpha(1)-adreno- receptor antagonist prazosin (0.2 mg x kg(-1)) blocked MDMA-induced hyperthermia and its exacerbation by caffeine. Co-administration of a combination of MDMA with the PDE-4 inhibitor rolipram (0.025 mg x kg(-1)) and the adenosine A(1/2) receptor antagonist 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-C]quinazolin-5 amine 15943 (10 mg x kg(-1)) or the A(2A) receptor antagonist SCH 58261 (2 mg x kg(-1)) but not the A(1) receptor antagonist DPCPX (10 mg x kg(-1)) exacerbated MDMA-induced hyperthermia. CONCLUSIONS AND IMPLICATIONS: A mechanism comprising 5 HT and catecholamines is proposed to mediate MDMA-induced hyperthermia. A combination of adenosine A(2A) receptor antagonism and PDE inhibition can account for the exacerbation of MDMA-induced hyperthermia by caffeine. PMID- 20590586 TI - Transfer of the glycosylphosphatidylinositol-anchored 5'-nucleotidase CD73 from adiposomes into rat adipocytes stimulates lipid synthesis. AB - BACKGROUND AND PURPOSE: In addition to predominant localization at detergent insoluble, glycolipid-enriched plasma membrane microdomains (DIGs), glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-proteins) have been found associated with lipid droplets (LDs) and adiposomes. Adiposomes are vesicles that are released from adipocytes in response to anti-lipolytic and lipogenic signals, such as H(2)O(2), palmitate and the antidiabetic sulfonylurea drug, glimepiride, and harbour (c)AMP-degrading GPI-proteins, among them the 5 nucleotidase CD73. Here the role of adiposomes in GPI-protein-mediated information transfer was studied. EXPERIMENTAL APPROACH: Adiposomes were incubated with isolated rat adipocytes under various conditions. Trafficking of CD73 and lipid synthesis were analysed. KEY RESULTS: Upon blockade of GPI-protein trafficking, CD73 specifically associated with DIGs of small, and to a lower degree, large, adipocytes. On reversal of the blockade, CD73 appeared at cytosolic LD in time- adiposome concentration- and signal (H(2)O(2) > glimepiride > palmitate)-dependent fashion. The salt- and carbonate-resistant association of CD73 with structurally intact DIGs and LD was dependent on its intact GPI anchor. Upon incubation with small and to a lower degree, large adipocytes, adiposomes increased lipid synthesis in the absence or presence of H(2)O(2), glimepiride and palmitate and improved the sensitivity toward these signals. Upregulation of lipid synthesis by adiposomes was dependent on the translocation of CD73 with intact GPI anchors from DIGs to LD. CONCLUSIONS: The signal-induced transfer of GPI-anchored CD73 from adiposomes via DIGs to LD of adipocytes mediates paracrine upregulation of lipid synthesis within the adipose tissue. PMID- 20590587 TI - The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone. AB - BACKGROUND AND PURPOSE: There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug-drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored. EXPERIMENTAL APPROACH: A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg x kg(-1) and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session. KEY RESULTS: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and C(max) (-0.71 < Spearman correlation coefficient rhos < -0.92). Oxymorphone C(max) was 62% and 75% lower in PM than EM and UM. Noroxymorphone C(max) reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone C(max) by 40% and 80%, and increased noroxycodone AUC(infinity) by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC(infinity) and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. CONCLUSIONS AND IMPLICATIONS: Drug-drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. PMID- 20590588 TI - Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. AB - BACKGROUND AND PURPOSE: The major drug-metabolizing enzymes for the oxidation of oxycodone are CYP2D6 and CYP3A. A high interindividual variability in the activity of these enzymes because of genetic polymorphisms and/or drug-drug interactions is well established. The possible role of an active metabolite in the pharmacodynamics of oxycodone has been questioned and the importance of CYP3A mediated effects on the pharmacokinetics and pharmacodynamics of oxycodone has been poorly explored. EXPERIMENTAL APPROACH: We conducted a randomized crossover (five arms) double-blind placebo-controlled study in 10 healthy volunteers genotyped for CYP2D6. Oral oxycodone (0.2 mg x kg(-1)) was given alone or after inhibition of CYP2D6 (with quinidine) and/or of CYP3A (with ketoconazole). Experimental pain (cold pressor test, electrical stimulation, thermode), pupil size, psychomotor effects and toxicity were assessed. KEY RESULTS: CYP2D6 activity was correlated with oxycodone experimental pain assessment. CYP2D6 ultra rapid metabolizers experienced increased pharmacodynamic effects, whereas cold pressor test and pupil size were unchanged in CYP2D6 poor metabolizers, relative to extensive metabolizers. CYP2D6 blockade reduced subjective pain threshold (SPT) for oxycodone by 30% and the response was similar to placebo. CYP3A4 blockade had a major effect on all pharmacodynamic assessments and SPT increased by 15%. Oxymorphone C(max) was correlated with SPT assessment (rho(S)= 0.7) and the only independent positive predictor of SPT. Side-effects were observed after CYP3A4 blockade and/or in CYP2D6 ultra-rapid metabolizers. CONCLUSIONS AND IMPLICATIONS: The modulation of CYP2D6 and CYP3A activities had clear effects on oxycodone pharmacodynamics and these effects were dependent on CYP2D6 genetic polymorphism. PMID- 20590589 TI - A novel quinone-based derivative (DTNQ-Pro) induces apoptotic death via modulation of heat shock protein expression in Caco-2 cells. AB - BACKGROUND AND PURPOSE: The resistance of human colon adenocarcinoma cells to antineoplastic agents may be related to the high endogenous expression of stress proteins, including the family of heat shock proteins (HSPs). Recently, a quinone based pentacyclic derivative, DTNQ-Pro, showed high cytotoxic activity in human colon carcinoma cell lines. The aim of the present study was to determine the precise cellular mechanisms of this cytotoxic action of DTNQ-Pro. EXPERIMENTAL APPROACH: Using human colorectal carcinoma-derived Caco-2 cells as a model, we studied the effects of DTNQ-Pro on cellular viability and oxidative stress; HSP70 and HSP27 accumulation; and cell cycle, differentiation and apoptosis. KEY RESULTS: Incubation of Caco-2 cells with DTNQ-Pro reduced cell growth and increased the levels of reactive oxygen species in mitochondria. After 48 h of treatment, cells surviving showed an increased expression of Mn-superoxide dismutase (SOD), nitric oxide production and membrane lipid peroxidation. Treatment with DTNQ-Pro decreased HSP70 expression, and redistributed HSP27 and vimentin within the cell. DTNQ-Pro down-regulated the expression of A and B cyclins with arrest of the cell cycle in S phase and increased cellular differentiation. A second treatment of Caco-2 cells with DTNQ-Pro induced cellular death by activation of the apoptotic pathway. CONCLUSIONS AND IMPLICATIONS: DTNQ-Pro causes Caco-2 cell death by induction of apoptosis via inhibition of HSP70 accumulation and the intracellular redistribution of HSP27. These findings suggest the potential use of DTNQ-Pro in combination chemotherapy for colon cancer. PMID- 20590590 TI - A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. AB - BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. EXPERIMENTAL APPROACH: Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio-specific derivatization agent monobromobimane, followed by reversed-phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H(2)S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H(2)S/HS(-) were concomitantly measured using an amperometric sensor. KEY RESULTS: Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis bimane derivative were validated via reversed-phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4-0.9 microM. Intravenous administration of sodium sulphide solution (2-20 mg x kg(-1) x h(-1)) or inhalation of H(2)S gas (50-400 ppm) elevated reactive sulphide in blood in a dose-dependent manner. Each 1 mg x kg(-1) x h(-1) of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H(2)S gas inhalation. CONCLUSIONS AND IMPLICATIONS: The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H(2)S gas. PMID- 20590591 TI - Simultaneous detection of intracellular target and off-target binding of small molecule cancer drugs at nanomolar concentrations. AB - BACKGROUND AND PURPOSE: In vitro assays that determine activities of drug candidates with isolated targets have only limited predictive value for activities in cellular assays. Poor membrane permeability and off-target binding are major reasons for such discrepancies. However, it still difficult to directly analyse off-target binding at the same time as target binding, on a subcellular level. Here, we present a combination of fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) as a solution to this problem. EXPERIMENTAL APPROACH: The well-established dihydrofolate reductase inhibitor methotrexate and the kinase inhibitors PD173956 and purvalanol B were conjugated via polyethylene glycol linkers with the fluorophore Cy5. The cellular uptake and subcellular distribution of these compounds in single human cancer derived cells were investigated by confocal laser scanning microscopy. In addition, molecular interactions inside the cell with the respective target proteins and off-target binding were detected simultaneously in the nanomolar range by FCCS and FCS, respectively, using cells expressing green fluorescent protein fusion proteins of dihydrofolate reductase and Abelson kinase 1. KEY RESULTS: Large differences in the interaction patterns were found for these compounds. For methotrexate-Cy5, drug-target interactions could be detected and dissociation constants determined. In contrast, PD173956-Cy5 showed strong interactions with intracellular high-molecular weight structures, other than its target. CONCLUSIONS AND IMPLICATIONS: The combination of FCS and FCCS provides a powerful means to assess subcellular pharmacokinetics and dynamics of drug candidates at nanomolar concentrations. PMID- 20590592 TI - The xanthine derivative KMUP-1 inhibits models of pulmonary artery hypertension via increased NO and cGMP-dependent inhibition of RhoA/Rho kinase. AB - BACKGROUND AND PURPOSE: KMUP-1 is known to increase cGMP, enhance endothelial nitric oxide synthase (eNOS) and suppress Rho kinase (ROCK) expression in smooth muscle. Here, we investigated the mechanism of action of KMUP-1 on acute and chronic pulmonary artery hypertension (PAH) in rats. EXPERIMENTAL APPROACH: We measured pulmonary vascular contractility, wall thickening, eNOS immunostaining, expressions of ROCK II, RhoA activation, myosin phosphatase target subunit 1 (MYPT1) phosphorylation, eNOS, soluble guanylyl cyclase (sGC), protein kinase G (PKG) and phosphodiesterase 5A (PDE-5A), blood oxygenation and cGMP/cAMP, and right ventricular hypertrophy (RVH) in rats. KEY RESULTS: In rings of intact pulmonary artery (PA), KMUP-1 relaxed the vasoconstriction induced by phenylephrine (10 microM) or the thromboxane A(2)-mimetic U46619 (0.5 microM). In endothelium-denuded PA rings, this relaxation was reduced. In acute PAH induced by U46619 (2.5 microg x kg(-1) x min(-1), 30 min), KMUP-1 relaxed vasoconstriction by enhancing levels of eNOS, sGC and PKG, suppressing those of PDE-5A, RhoA/ROCK II activation and MYPT1 phosphorylation, and restoring oxygenation in blood and cGMP/cAMP in plasma. Incubating smooth muscle cells from PA (PASMCs) with KMUP-1 inhibited thapsigargin-induced Ca(2+) efflux and angiotensin II-induced Ca(2+) influx. In chronic PAH model induced by monocrotaline, KMUP-1 increased eNOS and reduced RhoA/ROCK II activation/expression, PA wall thickening, eNOS immunostaining and RVH. KMUP-1 and sildenafil did not inhibit monocrotaline-induced PDE-5A expression. CONCLUSION AND IMPLICATIONS: KMUP-1 decreased PAH by enhancing NO synthesis by eNOS, with consequent cGMP-dependent inhibition of RhoA/ROCK II and Ca(2+) desensitization in PASMCs. KMUP-1 has the potential to reduce vascular resistance, remodelling and RVH in PAH. PMID- 20590593 TI - Purinoreceptor-mediated current in myocytes from renal resistance arteries. AB - BACKGROUND AND PURPOSE: Ionotropic purinoreceptors (P2X) in renal vascular smooth muscle cells (RVSMCs) are involved in mediating the sympathetic control and paracrine regulation of renal blood flow (RBF). Activation of P2X receptors elevates [Ca(2+)](i) in RVSMCs triggering their contraction, leading to renal vasoconstriction and decrease of RBF. The goal of the present work was to characterize the P2X receptor-mediated ionic current (I(P2X)) and to identify the types of P2X receptors expressed in myocytes isolated from interlobar and arcuate arteries of rat kidney. EXPERIMENTAL APPROACH: The expression of P2X receptors in isolated RVSMCs was analysed by reverse transcription (RT)-PCR. I(P2X) and membrane potential were recorded using the amphotericin B-perforated patch method. KEY RESULTS: RT-PCR analysis on single RVSMCs showed the presence of genes encoding P2X1 and P2X4 receptors. Under voltage clamp conditions, the selective P2X receptor agonist alphabeta-methylene ATP (alphabeta-meATP) evoked I(P2X) similar to that induced by ATP. Under current clamp conditions, both ATP and alphabeta-meATP evoked a spike-like membrane depolarization followed by a sustained depolarization, linking P2X receptors in RVSMCs to sympathetic control of renal vascular tone. A selective antagonist of P2X1 receptors, NF279, reduced I(P2X) amplitude by approximately 65% concentration-dependently manner within the nanomolar to sub-micromolar range. The residual current was resistant to micromolar concentrations of NF279, but was inhibited by sub-millimolar to millimolar concentrations of NF279. CONCLUSIONS AND IMPLICATIONS: Two types of functional P2X receptors, monomeric P2X1 and heteromeric P2X1/4 receptors, are expressed in RVSMCs. Our study has identified important targets for possible pharmacological intervention in the sympathetic control of renal circulation. PMID- 20590594 TI - Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer. AB - BACKGROUND AND PURPOSE: Pancreatic cancer is a highly aggressive malignancy, and improvement in systemic therapy is necessary to treat this frequently encountered metastatic disease. The current targeted agents used in combination with gemcitabine improved objective response rates, but with little or no improvements in survival and also increased toxicities in pancreatic cancer patients. Recently, we showed that the triterpenoid cucurbitacin B inhibited tumour growth in pancreatic cancer cells by inhibition of the JAK/STAT pathway, and synergistically increased antiproliferative effects of gemcitabine in vitro. EXPERIMENTAL APPROACH: The anti-tumour effects and toxicities of cucurbitacin B in combination with gemcitabine were tested against human pancreatic cancer cells in a murine xenograft model. KEY RESULTS: Combined therapy with cucurbitacin B and gemcitabine at relatively low doses (0.5 mg x kg(-1) and 25 mg x kg(-1) respectively) resulted in highly significant tumour growth inhibition of pancreatic cancer xenografts (up to 79%). Remarkably, this therapy was well tolerated by the animals, as shown by histology of visceral organs, analysis of serum chemistry, full blood counts and bone marrow colony numbers. Western blot analysis of the tumour samples of mice who received both cucurbitacin B and gemcitabine, revealed stronger inhibition of Bcl-XL, Bcl-2 and c-myc, and higher activation of the caspase cascades, than mice treated with either agent alone. CONCLUSIONS AND IMPLICATIONS: Combination of cucurbitacin B and gemcitabine had profound anti-proliferative effects in vivo against xenografts of human pancreatic cancer cells, without any significant signs of toxicity. This promising combination should be examined in therapeutic trials of pancreatic cancer. PMID- 20590595 TI - ENaC-mediated effects assessed by MRI in a rat model of hypertonic saline-induced lung hydration. AB - BACKGROUND AND PURPOSE: The epithelial sodium channel (ENaC) regulates airway mucosal hydration and mucus clearance. The lack of such regulation in cystic fibrosis patients leads to desiccation of the airway lumen, resulting in mucostasis that establishes the environment for infections. Osmotic agents and negative ENaC regulators can be used to restore mucosal hydration. We aimed to assess whether: (i) osmotically driven fluid flux into the rat lung could be quantified in vivo by magnetic resonance imaging (MRI); and (ii) the MRI signals could be modulated through the regulation of ENaC function. EXPERIMENTAL APPROACH: Lung images from spontaneously breathing rats were acquired following intra-tracheal (i.t.) administration of physiological or hypertonic saline (HS). Compounds known to modulate the ENaC function were given i.t. prior to saline. Volumes of fluid signals were quantified on the images. KEY RESULTS: A tonicity dependent increase in lung fluid was demonstrated following HS administration. Pretreatment with the ENaC blockers, amiloride or 552-02, resulted in an enhancement of HS-induced lung fluid signals, which were detectable for up to 4 h, consistent with a role for ENaC in fluid clearance. Aprotinin, a serine protease inhibitor that attenuates ENaC function, likewise enhanced the HS induced increase in lung fluid signal, while alpha(1)-anti-trypsin was without significant effect. CONCLUSIONS AND IMPLICATIONS: Proton MRI provides a non invasive technique for studying modulators of lung fluid hydration in rat lung in vivo. The pharmacological sensitivity of MRI-detected fluid signals is consistent with ENaC-mediated fluid reabsorption after HS. This target-related readout may be used to characterize new ENaC modulators. PMID- 20590596 TI - Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumours. AB - BACKGROUND AND PURPOSE: The overexpression of epidermal growth factor receptor (EGFR) and its mutated variant EGFRvIII occurs in 50% of glioblastoma multiforme. We developed antibody fragments against EGFR/EGFRvIII for molecular imaging and/or therapeutic targeting applications. EXPERIMENTAL APPROACH: An anti EGFR/EGFRvIII llama single-domain antibody (EG(2)) and two higher valency format constructs, bivalent EG(2)-hFc and pentavalent V2C-EG(2) sdAbs, were analysed in vitro for their binding affinities using surface plasmon resonance and cell binding studies, and in vivo using pharmacokinetic, biodistribution, optical imaging and fluorescent microscopy studies. KEY RESULTS: Kinetic binding analyses by surface plasmon resonance revealed intrinsic affinities of 55 nM and 97 nM for the monovalent EG(2) to immobilized extracellular domains of EGFR and EGFRvIII, respectively, and a 10- to 600-fold increases in apparent affinities for the multivalent binders, V2C-EG(2) and EG(2)-hFc, respectively. In vivo pharmacokinetic and biodistribution studies in mice revealed plasma half-lives for EG(2), V2C-EG(2) and EG(2)-hFc of 41 min, 80 min and 12.5 h, respectively, as well as a significantly higher retention of EG(2)-hFc compared to the other two constructs in EGFR/EGFRvIII-expressing orthotopic brain tumours, resulting in the highest signal in the tumour region in optical imaging studies. Time domain volumetric optical imaging fusion with high-resolution micro-computed tomography of microvascular brain network confirmed EG(2)-hFc selective accumulation/retention in anatomically defined tumour regions. CONCLUSIONS: Single domain antibodies can be optimized for molecular imaging applications by methods that improve their apparent affinity and prolong plasma half-life and, at the same time, preserve their ability to penetrate tumour parenchyma. PMID- 20590598 TI - Being mindful of seven-transmembrane receptor 'guests' when assessing agonist selectivity. AB - The time-honored approach of quantifying agonist selectivity through measurement of agonist affinity with binding and efficacy through potency ratios in model assays for prediction of effect in therapeutic systems can fall short of providing useful answers for functionally selective agonists. Agonists are now known to have pluridimensional efficacies that are associated with selected signalling pathways coupled to the receptor. This necessitates specifically tailored assay formats to measure pre-determined efficacies of ligands to characterize agonist selectivity fully. If such assays can access signalling that directly emanates from the interaction of the agonist-bound receptor and a cytosolic signalling protein, then the Black/Leff operational model can be used to specifically quantify 'transduction ratios' (tau/K(A)) that fully characterize selective activation of signalling pathways by a given agonist. As whole-cell processing of pleiotropic signalling cascades imposes cell-specific phenotypic agonist profiles, ultimately the assessment of agonist selectivity is most reliably done in the therapeutically relevant primary cell system. PMID- 20590597 TI - The role of monoamines in the changes in body temperature induced by 3,4 methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. AB - Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters [5 hydroxytryptamine (5-HT), dopamine and noradrenaline], both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central alpha(2A)-adrenoceptors and peripheral alpha(1)-adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and beta(3)-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. PMID- 20590599 TI - The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3 adrenoceptors. AB - BACKGROUND AND PURPOSE: There are two important properties of receptor-ligand interactions: affinity (the ability of the ligand to bind to the receptor) and efficacy (the ability of the receptor-ligand complex to induce a response). Ligands are classified as agonists or antagonists depending on whether or not they have efficacy. In theory, it is possible to develop selective agonists based on selective affinity, selective intrinsic efficacy or both. This study examined the affinity and intrinsic efficacy of 31 beta-adrenoceptor agonists at the three human beta-adrenoceptors to determine whether the current agonists are subtype selective because of affinity or intrinsic efficacy. EXPERIMENTAL APPROACH: Stable clonal CHO-K1 cell lines, transfected with either the human beta(1), beta(2) or beta(3)-adrenoceptor, were used, and whole-cell [(3)H]-CGP 12177 radioligand binding and [(3)H]-cAMP accumulation were measured. KEY RESULTS: Several agonists were found to be highly subtype selective because of selective affinity (e.g. salmeterol and formoterol, for the beta(2)-adrenoceptor over the beta(1) or beta(3)), while others (e.g. isoprenaline) had little affinity selectivity. However, the intrinsic efficacy of salmeterol, formoterol and isoprenaline was similar across all three receptor subtypes. Other ligands (e.g. denopamine for beta(1); clenbuterol, AZ 40140d, salbutamol for beta(2)) were found to have subtype-selective intrinsic efficacy. Several ligands appeared to activate two agonist conformations of the beta(1)- and beta(3)-adrenoceptors. CONCLUSIONS AND IMPLICATIONS: There are agonists with subtype selectivity based upon both selective affinity and selective intrinsic efficacy. Therefore, there is scope to develop better selective agonists based upon both selective affinity and selective intrinsic efficacy. PMID- 20590600 TI - Celecoxib treatment restores pharmacosensitivity in a rat model of pharmacoresistant epilepsy. AB - BACKGROUND AND PURPOSE: A functional link between seizure-induced P-glycoprotein overexpression at the blood-brain barrier and therapeutic failure has been suggested by several studies using rodent epilepsy models and human epileptic tissue. Recently, we reported that interference with the mechanisms that up regulate P-glycoprotein in response to seizure activity might provide a novel approach to control its expression in the epileptic brain. Based on these data, we hypothesized that blocking the appropriate signalling cascade by cyclooxygenase-2 inhibition should improve brain penetration of antiepileptic drugs and help to overcome drug resistance. EXPERIMENTAL APPROACH: Effects of the selective cyclooxygenase-2 inhibitor celecoxib on the response to the P glycoprotein substrate, phenobarbital, was evaluated in a chronic model of drug resistant temporal lobe epilepsy in rats. Drug-resistant rats selected from this model exhibit a marked overexpression of P-glycoprotein in the hippocampus and other limbic brain regions. KEY RESULTS: Responders and non-responders were selected from a group of rats with spontaneous recurrent seizures after prolonged treatment with phenobarbital at maximum tolerated doses. The efficacy of phenobarbital was re-evaluated following a 6 day treatment with celecoxib and the frequency of spontaneous recurrent seizures was significantly reduced in both groups of rats, phenobarbital responders or non-responders selected from the previous drug trial. CONCLUSIONS AND IMPLICATIONS: Pretreatment with the cyclooxygenase-2 inhibitor restored the anticonvulsant activity of phenobarbital in rats that failed to exhibit a relevant response before celecoxib treatment. Our data provide further support for a novel therapeutic approach to overcome transporter-mediated drug resistance in epilepsies. PMID- 20590601 TI - Riluzole protects against cardiac ischaemia and reperfusion damage via block of the persistent sodium current. AB - BACKGROUND AND PURPOSE: Current strategies to ameliorate cardiac ischaemic and reperfusion damage, including block of the sodium-hydrogen exchanger, are therapeutically ineffective. Here we propose a different approach, block of the persistent sodium current (INaP). EXPERIMENTAL APPROACH: Left ventricular pressure was measured as an index of functional deficit in isolated, Langendorff perfused, hearts from adult rats, subjected to 30 min global ischaemia and reperfusion with vehicle only (control) or riluzole (1-10 microM) in the perfusate. Cell shortening and intracellular Ca2+ concentrations [Ca2+](i) were measured in adult rat isolated myocytes subjected to hypoxia and re-oxygenation. The block of transient and persistent sodium currents by concentrations of riluzole between 0.01 and 100 microM were assessed in rat isolated myocytes using patch clamp techniques. KEY RESULTS: In perfused hearts, riluzole produced a concentration-dependent cardioprotective action, with minor protection from 1 microM and produced rapid and almost complete recovery upon reperfusion from 3 and 10 microM. In isolated myocytes, riluzole at 3 and 10 microM greatly attenuated or prevented the hypoxia- and reperfusion-induced rise in [Ca2+](i) and the contractile deficit. In patch clamp experiments, riluzole blocked the persistent sodium current with an IC(50) of 2.7 microM, whereas the block of the transient sodium current was only apparent at concentrations above 30 microM. CONCLUSIONS AND IMPLICATIONS: Riluzole preferentially blocked INaP and was protective in cardiac ischaemia and reperfusion. Thus block of the persistent sodium current would be a viable method of ameliorating cardiac ischaemic and reperfusion damage. PMID- 20590602 TI - Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy. AB - BACKGROUND AND PURPOSE: 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN - 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) - and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known. EXPERIMENTAL APPROACH: Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each study period. KEY RESULTS: Median baseline levels in 17 patients of 6-TGDP, 6 TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 x 10(8) red blood cells respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 6 TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio did not change during the study, but 6-MMPR/6-TGN ratios decreased. CONCLUSIONS AND IMPLICATIONS: Individual 6-TGN metabolites increased after addition of 5-ASA, but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA. PMID- 20590603 TI - Enhancement of mesenteric artery contraction to 5-HT depends on Rho kinase and Src kinase pathways in the ob/ob mouse model of type 2 diabetes. AB - BACKGROUND AND PURPOSE: Arteries from hypertensive subjects are reportedly hyperresponsive to 5-hydroxytryptamine (5-HT), but it remains unclear whether this is true in chronic type 2 diabetes. We have assessed responses to 5-HT shown by mesenteric arteries from type 2 diabetic ob/ob mice (27-32 weeks old) and have identified the molecular mechanisms involved. EXPERIMENTAL APPROACH: Contractions of mesenteric rings to 5-HT were examined in vitro. Activation of mesenteric RhoA, Rho kinase and Src was measured by Western blotting or by modified enzyme linked immunosorbent assay. KEY RESULTS: Concentration-dependent contractions to 5-HT were greater in mesenteric rings from the ob/ob than in those from the age matched control ('Lean') group. In each group, there was no significant change in the 5-HT-induced contractions after inhibition of nitric oxide synthase (with N(G)-nitro-L-arginine), of cyclooxygenase (with indomethacin) or of protein kinase C (with chelerythrine). However inhibition of the MEK/ERK pathway (with PD98059) decreased the response to 5-HT. Although the diabetes-related enhancement of the 5-HT response was preserved with each of these inhibitors, enhancement was abolished by a Rho kinase inhibitor (Y27632) and by Src kinase inhibitors (PP1 analogue or Src kinase inhibitor I). 5-HT-induced activation of RhoA, Rho kinase and Src kinase in mesenteric arteries was greater in the ob/ob than in the Lean group, but the expression of RhoA, Rho kinase isoforms and Src did not differ between these groups. CONCLUSIONS AND IMPLICATIONS: These results suggest that the enhancement of 5-HT-induced contraction in mesenteric arteries from ob/ob mice may be attributable to increased activation of RhoA/Rho kinase and Src kinase. PMID- 20590604 TI - WAY-318068: a novel, potent and selective noradrenaline re-uptake inhibitor with activity in rodent models of pain and depression. AB - BACKGROUND AND PURPOSE: Antidepressants, which raise the CNS concentrations of 5 HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity. EXPERIMENTAL APPROACH: In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3 (methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one). KEY RESULTS: WAY-318068 is a potent and effective inhibitor of the NET with a K(i) of 8.7 nM in a binding assay, and an IC(50) of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits. CONCLUSIONS AND IMPLICATIONS: Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain. PMID- 20590605 TI - AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder. AB - BACKGROUND AND PURPOSE: AE9C90CB (N- [(1R, 5S, 6R)-3-azabicyclo [3.1.0] hex-6 ylmethyl]-2-hydroxy-N-methyl-2, 2-diphenylacetamide), a novel muscarinic receptor antagonist, was synthesized for the treatment of overactive bladder. Here we describe the in vitro and in vivo profiles of AE9C90CB for action in bladder over salivary gland and compare it with four agents already in clinical use (tolterodine, oxybutynin, solifenacin and darifenacin). EXPERIMENTAL APPROACH: Radioligand binding assay and isolated tissue-based functional assay were used to evaluate affinity, potency, and receptor subtype selectivity of compounds. Inhibition of carbachol-induced increase in intravesicular pressure and salivary secretion were measured in anaesthetized rabbits to assess the functional selectivity. KEY RESULTS: In vitro radioligand binding study using human recombinant muscarinic receptors showed that AE9C90CB had greater affinity for M(3) muscarinic receptors with pKi of 9.90 +/- 0.11 and was 20-fold more selective for M(3) than for M(2) muscarinic receptors. AE9C90CB exhibited an unsurmountable antagonism on rat bladder strips (pK(B), 9.13 +/- 0.12). In anaesthetized rabbits after intravenous administration, AE9C90CB dose dependently inhibited carbachol-induced increase in intravesicular pressure and salivary secretion, and exhibited functional selectivity for urinary bladder over salivary gland which was ninefold better than that of oxybutynin. CONCLUSIONS AND IMPLICATIONS: We have identified AE9C90CB, a compound exhibiting moderate selectivity for M(3) over M(2) receptors but greater selectivity for urinary bladder over salivary gland than oxybutynin, tolterodine, solifenacin and darifenacin. Therefore, AE9C90CB may be a promising compound for the treatment of overactive bladder with reduced potential to cause dry mouth than currently available antimuscarinic drugs. PMID- 20590606 TI - Oral sildenafil increases skin hyperaemia induced by iontophoresis of sodium nitroprusside in healthy volunteers. AB - BACKGROUND AND PURPOSE: Sildenafil, a specific inhibitor of phosphodiesterase 5A (PDE5A), is currently tested as a treatment for severe Raynaud's phenomenon. Here, we tested whether sildenafil, alone or combined with local sodium nitroprusside (SNP) delivered through skin iontophoresis, increased forearm cutaneous blood conductance in healthy volunteers, and to assess how well this combination was tolerated. EXPERIMENTAL APPROACH: Ten healthy volunteers were enrolled. Variations in cutaneous vascular conductance (CVC) following oral administration of 50 or 100 mg of sildenafil with or without SNP iontophoresis were expressed as a percentage of maximal CVC, and were monitored using laser Doppler imaging. SNP iontophoresis was performed on the ventral surface of the forearm, 1 h after application of lidocaine/prilocaine cream. KEY RESULTS: Sildenafil at 100 mg, but not 50 mg, increased overall responses (area under the curve) (44%) and peak responses (29%) to SNP iontophoresis. Sildenafil at 100 mg, but not 50 mg, increased baseline CVC (75%). Incidence of headache was not changed when SNP iontophoresis was combined with sildenafil. One episode of symptomatic arterial hypotension occurred in a volunteer given 50 mg sildenafil, 30 min after the beginning of SNP iontophoresis. CONCLUSIONS AND IMPLICATIONS: Oral sildenafil at 100 mg potentiated local skin hyperaemia induced by SNP iontophoresis, with no increased incidence of headaches. The combination of oral specific PDE5A inhibitor and nitrates administered through skin iontophoresis deserves further investigation in diseases such as severe Raynaud's phenomenon, with particular attention to the incidence of arterial hypotension. PMID- 20590607 TI - Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle. AB - BACKGROUND AND PURPOSE: The mechanism(s) of action responsible for the beneficial effects of phosphodiesterase 5 (PDE5) inhibitors including sildenafil on lower urinary tract symptoms suggestive of benign prostate hyperplasia are unclear. In particular, the role of the NO-cGMP signalling pathway in regulating human bladder dome smooth muscle relaxation is questionable. Thus, we assessed the ability of a PDE5 inhibitor, sildenafil, to relax such tissue, and identified the signalling pathways involved in this relaxation. EXPERIMENTAL APPROACH: Human bladder samples were obtained from 20 patients with no overactive bladder undergoing cystectomy for bladder cancer. Detrusor strips were mounted isometrically in Krebs-HEPES solution. Concentration-response curves for sildenafil (10 nM-30 microM) were generated in the presence of various inhibitors on carbachol-induced pre-contraction. KEY RESULTS: Sildenafil relaxed carbachol pre-contracted human detrusor strips, starting at 3 microM. This effect was not modified by NO donors, S-nitroso-N-acetylpenicillamine (10 microM) or sodium nitroprusside (300 nM), but was significantly inhibited by inhibition of guanylate cyclase (with ODQ, 10 microM) or adenylyl cyclase (with MDL-12,330A, 10 microM), by the ATP-sensitive potassium channel inhibitor, glibenclamide (10 microM), or inhibition of the large (with iberiotoxin, 30 nM) or small (with apamin, 100 nM) conductance calcium-activated potassium channels. CONCLUSIONS AND IMPLICATIONS: Sildenafil-induced relaxation of human detrusor smooth muscle involved cGMP-, cAMP- and K(+) channel-dependent signalling pathways, with a minor contribution from NO. The effect of this sildenafil-induced relaxation on the clinical benefit of PDE5 inhibitors on urinary storage symptoms in men deserves further investigation. PMID- 20590608 TI - Cell context-dependent activities of parthenolide in primary and metastatic melanoma cells. AB - BACKGROUND AND PURPOSE: Growing evidence implicates NF-kappaB as an important contributor to metastasis and increased chemoresistance of melanoma. Here, we report the effects of parthenolide on either untreated, cisplatin- or TNFalpha treated melanoma cell lines A375, 1205Lu and WM793, exhibiting different levels of constitutive NF-kappaB activity. EXPERIMENTAL APPROACH: Electrophoretic mobility shift assay was used to assess changes in NF-kappaB activity, and real time PCR to evaluate expression of NF-kappaB-regulated genes. Cell cycle arrest and apoptosis were assessed by flow cytometry. Cell death was also visualized by fluorescence microscopy. Migration was determined by scratch assay and invasiveness by Matrigel assay. KEY RESULTS: Parthenolide suppressed both constitutive and induced NF-kappaB activity in melanoma cells. This was accompanied by down-regulation of cancer-related genes, with NF-kappaB-binding sites in their promoters, including: Bcl-X(L), survivin, cyclin D1, interleukin 8 and matrix metalloproteinase 9. When the various effects of 6 microM parthenolide were compared, apoptosis associated with loss of mitochondrial membrane potential was most efficiently induced in 1205Lu cells, cell cycle arrest in G(0)/G(1) phase was observed in WM793 cells, and high metastatic potential was markedly reduced in A375 cells. These findings not only reflected differences between melanoma cell lines in basal expression of NF-kappaB-regulated genes, but also suggested other parthenolide targets involved in cell cycle progression, migration, invasiveness and survival. CONCLUSIONS: Inhibition of constitutive and therapeutically induced NF-kappaB pathway by parthenolide might be useful in the treatment of melanoma, although the diversity of changes induced in melanoma cells with different genetic backgrounds indicate context-dependent poly pharmacological properties of this compound. PMID- 20590609 TI - 9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol, from Eulophia ochreata, inhibits inflammatory signalling mediated by Toll-like receptors. AB - BACKGROUND AND PURPOSE: 9,10-Dihydro-2,5-dimethoxyphenanthrene-1,7-diol (RSCL 0520) is a phenanthrene isolated from Eulophia ochreata, one of the Orchidaceae family, known by local tradition to exhibit medicinal properties. However, no anti-inflammatory activity or any molecular mechanisms involved have been reported or elucidated. Here, for the first time, we evaluate the anti inflammatory properties of RSCL-0520 on responses induced by lipopolysaccharide (LPS) and mediated via Toll-like receptors (TLRs). EXPERIMENTAL APPROACH: The in vitro anti-inflammatory activities of RSCL-0520 were investigated in LPS stimulated monocytic cells, measuring activation of cytokine and inflammatory genes regulated by nuclear factor-kappaB (NF-kappaB). Tumour necrosis factor (TNF)-alpha levels in serum following LPS stimulation in mice and carrageenan induced paw oedema in rats were used as in vivo models. KEY RESULTS: Pretreatment with RSCL-0520 effectively inhibited LPS-induced, TLR4-mediated, NF-kappaB activated inflammatory genes in vitro, and reduced both LPS-induced TNF-alpha release and carrageenan-induced paw oedema in rats. Treatment with RSCL-0520 reduced LPS-stimulated mRNA expression of TNF-alpha, COX-2, intercellular adhesion molecule-1, interleukin (IL)-8 and IL-1beta, all regulated through NF kappaB activation. RSCL-0520, however, did not interfere with any cellular processes in the absence of LPS. CONCLUSIONS AND IMPLICATIONS: RSCL-0520 blocked signals generated by TLR4 activation, as shown by down-regulation of NF-kappaB regulated inflammatory cytokines. The inhibitory effect involved both MyD88 dependent and -independent signalling cascades. Our data elucidated the molecular mechanisms involved, and support the search for plant-derived TLR antagonists, as potential anti inflammatory agents. PMID- 20590610 TI - Activation of c-Jun N-terminal kinase is essential for mitochondrial membrane potential change and apoptosis induced by doxycycline in melanoma cells. AB - BACKGROUND AND PURPOSE: Tetracyclines were recently found to induce tumour cell death, but the early processes involved in this cytotoxic effect remain unclear. EXPERIMENTAL APPROACH: Viability of human and mouse melanoma cells was determined by MTT assay and flow cytometry. Kinase/protein/caspase activation was measured by Western blotting and mitochondrial membrane potential (DeltaPsi(m)) was analyzed by fluorescence microscopy and flow cytometry. KEY RESULTS: Human and mouse melanoma cells were treated with doxycycline or minocycline but only doxycycline was cytotoxic. This cell death (apoptosis) in A2058 cells involved activation of caspase-3, -7 and -9 and contributed to inhibition, by doxycycline, of matrix metalloproteinase (MMP) activity and migration of these cells. Doxycycline induced intra-cellular reactive oxygen species (ROS) production, apoptosis signal-regulated kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation at an early stage of treatment and induced mitochondrial cytochrome c release into cytosol and DeltaPsi(m) change during apoptosis. The JNK inhibitor/small interference RNA inhibited doxycycline-induced JNK activation, DeltaPsi(m) change and apoptosis, but did not affect ASK1 activation, suggesting a role of ASK1 for JNK activation in melanoma cell apoptosis. Two ROS scavengers reduced doxycycline-induced JNK and caspase activation, and apoptosis. Taken together, the results suggest the involvement of a ROS-ASK1-JNK pathway in doxycycline-induced melanoma cell apoptosis. CONCLUSIONS AND IMPLICATIONS: We have shown a promising cytotoxic effect of doxycycline on melanoma cells, have identified ROS and ASK1 as the possible initiators and have demonstrated that JNK activation is necessary for doxycycline induced melanoma cell apoptosis. PMID- 20590611 TI - Genistein aglycone improves skin repair in an incisional model of wound healing: a comparison with raloxifene and oestradiol in ovariectomized rats. AB - BACKGROUND AND PURPOSE: Oestrogen loss at menopause is frequently related to poor wound healing. Genistein has been tested in anti-ageing cosmetic preparations with interesting results on skin health. Here, we investigated the effects of the genistein aglycones, given systemically, in an incisional model of wound healing, compared to systemic oestradiol and raloxifene. EXPERIMENTAL APPROACH: Six months after ovariectomy (OVX), rats were randomly assigned to groups of 12 animals each and treated daily with genistein aglycone (1 and 10 mg kg(-1) s.c.), raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.) or 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.) for 12 weeks. Untreated OVX and sham OVX rats were used as controls. Then, 14 or 7 days before the end of the experiment, an incisional wound healing procedure was performed and skin specimens were collected to evaluate molecular, histological and functional measurements. KEY RESULTS: Seven and fourteen days after wounding, samples from OVX rats showed a decrease in transforming growth factor-beta1, tissue transglutaminase 2 and vascular endothelial growth factor compared to samples from sham OVX rats. Oestradiol, raloxifene and genistein all significantly modified this decrease, but the lowest genistein dose exerted a greater effect than the other treatments. Moreover, the lowest dose of genistein was the most effective in improving skin healing and wound tensile strength. CONCLUSIONS AND IMPLICATIONS: Genistein aglycone might be an alternative therapy for the management of skin wound healing. PMID- 20590612 TI - Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal regulated kinase/activator protein-1. AB - BACKGROUND AND PURPOSE: Population studies have revealed that treatment with the anti-diabetic drug metformin is significantly associated with reduced cancer risk, but the underlying mode of action has not been elucidated. The aim of our study was to determine the effect of metformin on tumour invasion and migration, and the possible mechanisms, using human fibrosarcoma HT-1080 cells. EXPERIMENTAL APPROACH: We employed invasion, migration and gelatin zymography assays to characterize the effect of metformin on HT-1080 cells. Transient transfection assays were performed to gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action. KEY RESULTS: Metformin inhibited migration and invasion by HT-1080 cells at sub-toxic concentrations. In these cells, metformin also suppressed phorbol-12-myristate-13-acetate (PMA)-enhanced levels of matrix metalloproteinases-9 (MMP-9) protein, mRNA and transcription activity through suppression of activator protein-1 (AP-1) activation. In addition, metformin strongly repressed the PMA-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and protein kinase C(PKC)alpha, whereas the phosphorylation of p38 mitogen-activated protein kinase was not affected by metformin. Metformin decreased the PMA-induced Ca(2+) influx. Furthermore, treatment with an intracellular Ca(2+) chelator (BAPTA-AM) or a selective calmodulin antagonist (W7) markedly decreased PMA induced MMP-9 secretion and cell migration, as well as activation of ERK and JNK/AP-1. CONCLUSIONS AND IMPLICATIONS: Metformin inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+)-dependent PKCalpha/ERK and JNK/AP-1-signalling pathways. Metformin therefore has the potential to be a potent anti-cancer drug in therapeutic strategies for fibrosarcoma metastasis. PMID- 20590613 TI - Induction of apoptosis by the ginsenoside Rh2 by internalization of lipid rafts and caveolae and inactivation of Akt. AB - BACKGROUND AND PURPOSE: Lipid rafts and caveolae are membrane microdomains with important roles in cell survival signalling involving the Akt pathway. Cholesterol is important for the structure and function of these microdomains. The ginsenoside Rh2 exhibits anti-tumour activity. Because Rh2 is structurally similar to cholesterol, we investigated the possibility that Rh2 exerted its anti tumour effect by modulating rafts and caveolae. EXPERIMENTAL APPROACH: A431 cells (human epidermoid carcinoma cell line) were treated with Rh2 and the effects on cell apoptosis, raft localization and Akt activation measured. We also examined the effects of over-expression of Akt and active-Akt on Rh2-induced cell death. KEY RESULTS: Rh2 induced apoptosis concentration- and time-dependently. Rh2 reduced the levels of rafts and caveolae in the plasma membrane and increased their internalization. Furthermore, Akt activity was decreased and consequently, Akt-dependent phosphorylation of Bad, a pro-survival protein, was decreased whereas the pro-apoptotic proteins, Bim and Bax, were increased upon Rh2 treatment. Unlike microdomain internalization induce by cholesterol depletion, Rh2-mediated internalization of rafts and caveolae was not reversed by cholesterol addition. Also, cholesterol addition did not restore Akt activation or rescue cells from Rh2-induced cell death. Rh2-induced cell death was attenuated in MDA-MB-231 cells over-expressing either wild-type or dominant active Akt. CONCLUSIONS AND IMPLICATIONS: Rh2 induced internalization of rafts and caveolae, leading to Akt inactivation, and ultimately apoptosis. Because elevated levels of membrane rafts and caveolae, and Akt activation have been correlated with cancer development, internalization of these microdomains by Rh2 could potentially be used as an anti-cancer therapy. PMID- 20590614 TI - Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir. AB - BACKGROUND AND PURPOSE: Lopinavir is extensively metabolized by cytochrome P450 3A (CYP3A) and is considered to be a substrate for the drug transporters ABCB1 (P glycoprotein) and ABCC2 (MRP2). Here, we have assessed the individual and combined effects of CYP3A, ABCB1 and ABCC2 on the pharmacokinetics of lopinavir and the relative importance of intestinal and hepatic metabolism. We also evaluated whether ritonavir increases lopinavir oral bioavailability by inhibition of CYP3A, ABCB1 and/or ABCC2. EXPERIMENTAL APPROACH: Lopinavir transport was measured in Madin-Darby canine kidney cells expressing ABCB1 or ABCC2. Oral lopinavir kinetics (+/- ritonavir) was studied in mice with genetic deletions of Cyp3a, Abcb1a/b and/or Abcc2, or in transgenic mice expressing human CYP3A4 exclusively in the liver and/or intestine. KEY RESULTS: Lopinavir was transported by ABCB1 but not by ABCC2 in vitro. Lopinavir area under the plasma concentration - time curve (AUC)(oral) was increased in Abcb1a/b(-/-) mice (approximately ninefold vs. wild-type) but not in Abcc2(-/-) mice. Increased lopinavir AUC(oral) (>2000-fold) was observed in cytochrome P450 3A knockout (Cyp3a(-/-)) mice compared with wild-type mice. No difference in AUC(oral) between Cyp3a(-/-) and Cyp3a/Abcb1a/b/Abcc2(-/-) mice was observed. CYP3A4 activity in intestine or liver, separately, reduced lopinavir AUC(oral) (>100 fold), compared with Cyp3a(-/-) mice. Ritonavir markedly increased lopinavir AUC(oral) in all CYP3A-containing mouse strains. CONCLUSIONS AND IMPLICATIONS: CYP3A was the major determinant of lopinavir pharmacokinetics, far more than Abcb1a/b. Both intestinal and hepatic CYP3A activity contributed importantly to low oral bioavailability of lopinavir. Ritonavir increased lopinavir bioavailability primarily by inhibiting CYP3A. Effects of Abcb1a/b were only detectable in the presence of CYP3A, suggesting saturation of Abcb1a/b in the absence of CYP3A activity. PMID- 20590615 TI - Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion. AB - BACKGROUND AND PURPOSE: Cannabidiol (CBD) is a phytocannabinoid, with anti apoptotic, anti-inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received either vehicle or CBD (10 or 50 microg kg(-1) i.v.) 10 min before 30 min coronary artery occlusion or CBD (50 microg kg(-1) i.v.) 10 min before reperfusion (2 h). The appearance of ventricular arrhythmias during the ischaemic and immediate post-reperfusion periods were recorded and the hearts excised for infarct size determination and assessment of mast cell degranulation. Arterial blood was withdrawn at the end of the reperfusion period to assess platelet aggregation in response to collagen. KEY RESULTS: CBD reduced both the total number of ischaemia-induced arrhythmias and infarct size when administered prior to ischaemia, an effect that was dose dependent. Infarct size was also reduced when CBD was given prior to reperfusion. CBD (50 microg kg(-1) i.v.) given prior to ischaemia, but not at reperfusion, attenuated collagen-induced platelet aggregation compared with control, but had no effect on ischaemia-induced mast cell degranulation. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that CBD is cardioprotective in the acute phase of I/R by both reducing ventricular arrhythmias and attenuating infarct size. The anti-arrhythmic effect, but not the tissue sparing effect, may be mediated through an inhibitory effect on platelet activation. PMID- 20590616 TI - Pharmacological pre- and post-conditioning with the sphingosine-1-phosphate receptor modulator FTY720 after myocardial ischaemia-reperfusion. AB - BACKGROUND AND PURPOSE: Our recent experiments demonstrated that the Sphingosine 1-phosphate (S1P) receptor agonist FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3 propanediol hydrochloride) improves recovery of function after myocardial ischaemia-reperfusion ex vivo. Therefore, we tested the hypothesis that pharmacological post-conditioning with FTY720 reduces infarct size after myocardial ischaemia-reperfusion in vivo. EXPERIMENTAL APPROACH: Myocardial ischaemia was induced in Wistar rats by ligation of the left coronary artery for 45 min. FTY720 (0.5 mg kg(-1)) was applied i.p. either once, before reperfusion, or twice, 24 h before myocardial ischaemia and before reperfusion. After 24 h reperfusion, we determined infarct size by triphenyltetrazolium chloride staining and granulocyte infiltration by immunohistochemistry. Tumour necrosis factor alpha (TNF)-alpha concentration was determined by elisa. S1P receptor expression was studied by Western blot. Calcium transients were evaluated in Indo-1-loaded cardiomyocytes. KEY RESULTS: In both groups, FTY720 significantly reduced lymphocyte count in peripheral blood. FTY720 treatment attenuated granulocyte infiltration and TNF-alpha protein expression in reperfused myocardium. However, both treatment regimens were not able to reduce infarct size. FTY720 increased mortality due to induction of fatal ventricular tachyarrhythmias when administered once before reperfusion, but protected against reperfusion arrhythmias when given 24 h prior to ischaemia. Pretreatment selectively down regulated S1P(1) receptor expression within the myocardium. S1P receptor agonists did not induce calcium deregulation in cardiomyocytes. CONCLUSIONS AND IMPLICATIONS: FTY720 applied during reperfusion did not reduce infarct size but increased mortality during myocardial ischaemia-reperfusion due to induction of arrhythmias. Pretreatment with FTY720 before ischaemia abrogated the deleterious pro-arrhythmic effects without reducing infarct size. PMID- 20590617 TI - Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1beta-stimulated human chondrocytes. AB - BACKGROUND AND PURPOSE: A main challenge in the therapy of osteoarthritis (OA) is the development of drugs that will modify the disease. Reliable test systems are necessary to enable an efficient screening of therapeutic substances. We therefore established a chondrocyte-based in vitro cell culture model in order to characterize different p38MAPK inhibitors. EXPERIMENTAL APPROACH: Interleukin 1beta (IL-1beta)-stimulated human OA chondrocytes were treated with the p38MAPK inhibitors Birb 796, pamapimod, SB203580 and the new substance CBS-3868. Birb 796 and SB203580-treated cells were analysed in a genome-wide microarray analysis. The efficacy of all inhibitors was characterized by quantitative gene expression analysis and the quantification of PGE(2) and NO release. KEY RESULTS: Microarray analysis revealed inhibitor-specific differences in gene expression. Whereas SB203580 had a broad effect on chondrocytes, Birb 796 counteracted the IL-1beta effect more specifically. All p38MAPK inhibitors significantly inhibited the IL 1beta-induced gene expression of COX-2, mPGES1, iNOS, matrix metalloproteinase 13 (MMP13) and TNFRSF11B, as well as PGE(2) release. Birb 796 and CBS-3868 showed a higher efficacy than SB203580 and pamapimod at inhibiting the expression of COX-2 and MMP13 genes, as well as PGE(2) release. In the case of mPGES1 and TNFRSF11B gene expression, CBS-3868 exceeded the efficacy of Birb 796. CONCLUSIONS AND IMPLICATIONS: Our test system could differentially characterize inhibitors of the same primary pharmaceutical target. It reflects processes relevant in OA and is based on chondrocytes that are mainly responsible for cartilage degradation. It therefore represents a valuable tool for drug screening in between functional in vitro testing and in vivo models. PMID- 20590618 TI - The role of nitric oxide, superoxide and peroxynitrite in the anti-arrhythmic effects of preconditioning and peroxynitrite infusion in anaesthetized dogs. AB - BACKGROUND AND PURPOSE: Both ischaemia preconditioning (PC) and the intracoronary infusion of peroxynitrite (PN) suppress ischaemia and reperfusion (I/R)-induced arrhythmias and the generation of nitrotyrosine (NT, a marker of PN). However, it is still unclear whether this latter effect is due to a reduction in nitric oxide (NO) or superoxide (O(2)(-)) production. EXPERIMENTAL APPROACH: Dogs anaesthetized with chloralose and urethane were infused, twice for 5 min, with either saline (control) or 100 nM PN, or subjected to similar periods of occlusion (PC), 5 min prior to a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Severities of ischaemia and ventricular arrhythmias, as well as changes in the coronary sinus nitrate/nitrite (NOx) levels were assessed throughout the experiment. The production of myocardial NOx, O(2)(-) and NT was determined following reperfusion. KEY RESULTS: Both PC and PN markedly suppressed the I/R-induced ventricular arrhythmias, compared to the controls, and increased NOx levels during coronary artery occlusion. Reperfusion induced almost the same increases in NOx levels in all groups, but superoxide production and, consequently, the generation of NT were significantly less in PC- and PN-treated dogs than in controls. CONCLUSIONS AND IMPLICATIONS: Since both PC and the administration of PN enhanced NOx levels during I/R, the attenuation of endogenous PN formation in these dogs is primarily due to a reduction in the amount of O(2) produced. Thus, the anti-arrhythmic effect of PC and PN can almost certainly be attributed to the preservation of NO availability during myocardial ischaemia. PMID- 20590620 TI - The PI-PLC inhibitor U-73122 is a potent inhibitor of the SERCA pump in smooth muscle. AB - In this issue MacMillan and McCarron in 2010 demonstrated that the phospholipase C (PLC) inhibitor U-73122 can potently inhibit Ca(2+) release from isolated smooth muscle cells independent of its effect on PLC. Their data suggest that the PLC inhibitor can block the sarcoplasmic/endoplasmic reticulum calcium ATPase pump in smooth muscle and cast doubt on the reliability of U-73122 as the main pharmacological tool to assess the role of the phosphotidyl inositol-PLC pathway in cellular signalling. PMID- 20590619 TI - Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: current status. AB - Activation of the renin-angiotensin-aldosterone system (RAAS) results in vasoconstriction, muscular (vascular and cardiac) hypertrophy and fibrosis. Established arterial stiffness and cardiac dysfunction are key factors contributing to subsequent cardiovascular and renal complications. Blockade of RAAS has been shown to be beneficial in patients with hypertension, acute myocardial infarction, chronic systolic heart failure, stroke and diabetic renal disease. An aggressive approach for more extensive RAAS blockade with combination of two commonly used RAAS blockers [ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)] yielded conflicting results in different patient populations. Combination therapy is also associated with more side effects, in particular hypotension, hyperkalaemia and renal impairment. Recently published ONTARGET study showed ACEI/ARB combination therapy was associated with more adverse effects without any increase in benefit. The Canadian Hypertension Education Program responded with a new warning: 'Do not use ACEI and ARB in combination'. However, the European Society of Cardiology in their updated heart failure treatment guidelines still recommended ACEI/ARB combo as a viable option. This apparent inconsistency among guidelines generates debate as to which approach of RAAS inhibition is the best. The current paper reviews the latest evidence of isolated ACEI or ARB use and their combination in cardiovascular diseases, and makes recommendations for their prescriptions in specific patient populations. PMID- 20590621 TI - The phospholipase C inhibitor U-73122 inhibits Ca(2+) release from the intracellular sarcoplasmic reticulum Ca(2+) store by inhibiting Ca(2+) pumps in smooth muscle. AB - BACKGROUND AND PURPOSE: The sarcoplasmic reticulum (SR) releases Ca(2+) via inositol 1,4,5-trisphosphate receptors (IP(3)R) in response to IP(3)-generating agonists. Ca(2+) release subsequently propagates as Ca(2+) waves. To clarify the role of IP(3) production in wave generation, the contribution of a key enzyme in the production of IP(3) was examined using a phosphoinositide-specific phospholipase C (PI-PLC) inhibitor, U-73122. EXPERIMENTAL APPROACH: Single colonic myocytes were voltage-clamped in whole-cell configuration and cytosolic Ca(2+) concentration ([Ca(2+)](cyto)) measured using fluo-3. SR Ca(2+) release was evoked either by activation of IP(3)Rs (by carbachol or photolysis of caged IP(3)) or ryanodine receptors (RyRs; by caffeine). KEY RESULTS: U-73122 inhibited carbachol-evoked [Ca(2+)](cyto) transients. The drug also inhibited [Ca(2+)](cyto) increases, evoked by direct IP(3)R activation (by photolysis of caged IP(3)) and RyR activation (by caffeine), which do not require PI-PLC activation. U-73122 also increased steady-state [Ca(2+)](cyto) and slowed the rate of Ca(2+) removal from the cytoplasm. An inactive analogue of U-73122, U 73343, was without effect on either IP(3)R- or RyR-mediated Ca(2+) release. CONCLUSIONS AND IMPLICATIONS: U-73122 inhibited carbachol-evoked [Ca(2+)](cyto) increases. However, the drug also reduced Ca(2+) release when evoked by direct activation of IP(3)R or RyR, slowed Ca(2+) removal and increased steady-state [Ca(2+)](cyto). These results suggest U-73122 reduces IP(3)-evoked Ca(2+) transients by inhibiting the SR Ca(2+) pump to deplete the SR of Ca(2+) rather than by inhibiting PI-PLC. PMID- 20590622 TI - Block and allosteric modulation of GABAergic currents by oenanthotoxin in rat cultured hippocampal neurons. AB - BACKGROUND AND PURPOSE: Oenanthotoxin (OETX), a polyacetylenic alcohol from plants of the genus Oenanthe, has recently been identified as potent inhibitor of GABA-evoked currents. However, the effects of OETX on the inhibitory postsynaptic currents (IPSCs), as well as the pharmacological mechanism(s) underlying its effects on GABA(A) receptors, remain unknown. The purpose of this study was to elucidate the mechanism underlying the inhibition of GABAergic currents by OETX. EXPERIMENTAL APPROACH: Effects of OETX on GABAergic currents were studied using the patch clamp technique on rat cultured hippocampal neurons. Miniature IPSCs (mIPSCs) were recorded in the whole-cell configuration, while the current responses were elicited by ultrafast GABA applications onto the excised patches. KEY RESULTS: OETX potently inhibited both mIPSCs and current responses, but its effect was much stronger on synaptic currents. Analysis of the effects of OETX on mIPSCs and evoked currents disclosed a complex mechanism: allosteric modulation of both GABA(A) receptor binding and gating properties and a non-competitive, probably open channel block mechanism. In particular, OETX reduced the binding rate and nearly abolished receptor desensitization. A combination of rapid clearance of synaptic GABA and OETX-induced slowing of binding kinetics is proposed to underlie the potent action of OETX on mIPSCs. CONCLUSIONS AND IMPLICATIONS: OETX shows a complex blocking mechanism of GABA(A) receptors, and the impact of this toxin is more potent on mIPSCs than on currents evoked by exogenous GABA. Such effects on GABAergic currents are compatible with the convulsions and epileptic-like activity reported for OETX. PMID- 20590623 TI - Effects of ionotropic glutamate receptor antagonists on rat dural artery diameter in an intravital microscopy model. AB - BACKGROUND AND PURPOSE: During migraine, trigeminal nerves may release calcitonin gene-related peptide (CGRP), inducing cranial vasodilatation and central nociception; hence, trigeminal inhibition or blockade of craniovascular CGRP receptors may prevent this vasodilatation and abort migraine headache. Several preclinical studies have shown that glutamate receptor antagonists affect the pathophysiology of migraine. This study investigated whether antagonists of NMDA (ketamine and MK801), AMPA (GYKI52466) and kainate (LY466195) glutamate receptors affected dural vasodilatation induced by alpha-CGRP, capsaicin and periarterial electrical stimulation in rats, using intravital microscopy. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were anaesthetized and the overlying bone was thinned to visualize the dural artery. Then, vasodilator responses to exogenous (i.v. alpha-CGRP) and endogenous (released by i.v. capsaicin and periarterial electrical stimulation) CGRP were elicited in the absence or presence of the above antagonists. KEY RESULTS: alpha-CGRP, capsaicin and periarterial electrical stimulation increased dural artery diameter. Ketamine and MK801 inhibited the vasodilator responses to capsaicin and electrical stimulation, while only ketamine attenuated those to alpha-CGRP. In contrast, GYKI52466 only attenuated the vasodilatation to exogenous alpha-CGRP, while LY466195 did not affect the vasodilator responses to endogenous or exogenous CGRP. CONCLUSIONS AND IMPLICATIONS: Although GYKI52466 has not been tested clinically, our data suggest that it would not inhibit migraine via vascular mechanisms. Similarly, the antimigraine efficacy of LY466195 seems unrelated to vascular CGRP-mediated pathways and/or receptors. In contrast, the cranial vascular effects of ketamine and MK801 may represent a therapeutic mechanism, although the same mechanism might contribute, peripherally, to cardiovascular side effects. PMID- 20590624 TI - Failure of Bay K 8644 to induce RhoA kinase-dependent calcium sensitization in rabbit blood vessels. AB - BACKGROUND AND PURPOSE: RhoA kinase (ROCK) participates in K(+) depolarization (KCl)-induced Ca(2+) sensitization of contraction. Whether constitutive, depolarization- or Ca(2+)-activated ROCK plays the major role in this signalling system remains to be determined. Here, we determined whether Bay K 8644, a dihydropyridine that promotes Ca(2+) channel clusters to operate in a persistent Ca(2+) influx mode, could cause ROCK-dependent Ca(2+) sensitization. EXPERIMENTAL APPROACH: Renal and femoral artery rings from New Zealand white rabbits were contracted with Bay K 8644. Tissues were frozen and processed to measure active RhoA and ROCK substrate (myosin phosphatase targeting subunit, MYPT1) and myosin light chain (MLC) phosphorylation, or loaded with fura-2 to measure intracellular free Ca(2+) ([Ca(2+)](i)). Effects of selective inhibitors of contraction were assessed in resting (basal) tissues and those contracted with Bay K 8644. KEY RESULTS: Bay K 8644 produced strong increases in [Ca(2+)](i), MLC phosphorylation and tension, but not in MYPT1 phosphorylation. ROCK inhibition by H-1152 abolished basal MYPT1-pT853, diminished basal MLC phosphorylation and inhibited Bay K 8644-induced increases in MLC phosphorylation and tension. MLC kinase inhibition by wortmannin abolished Bay K 8644-induced contraction and increase in MLC phosphorylation but did not inhibit basal MYPT1-pT853. H-1152 and wortmannin had no effect on MYPT1-pT696, but 1 microM staurosporine inhibited basal MYPT1 pT853, MYPT1-pT696 and MLC phosphorylation. CONCLUSIONS AND IMPLICATIONS: These data suggest that the constitutive activities of ROCK and a staurosporine sensitive kinase regulate basal phosphorylation of MYPT1, which participates along with activation of MLC kinase in determining the strength of contraction induced by the Ca(2+) agonist, Bay K 8644. PMID- 20590625 TI - Acurhagin-C, an ECD disintegrin, inhibits integrin alphavbeta3-mediated human endothelial cell functions by inducing apoptosis via caspase-3 activation. AB - BACKGROUND AND PURPOSE: Acurhagin, a member of versatile metalloproteinase disintegrins from Agkistrodon acutus venom, has been identified as a platelet aggregation inhibitor, previously. Here, acurhagin-C, the C-terminal Glu-Cys-Asp (ECD)-containing fragment of acurhagin, was evaluated for its biological activities and potential applications in anti-angiogenic therapy. EXPERIMENTAL APPROACH: Human umbilical vein endothelial cells (HUVECs) were treated with acurhagin-C to assay effects on viability, apoptosis, adhesion, migration, invasion, proliferation and angiogenesis. The recognition site and signalling involved for the interactions of acurhagin-C with HUVEC were determined using flow cytometric, electrophoresis and immunoblotting analyses. KEY RESULTS: Acurhagin-C decreased viability and induced apoptosis in HUVEC. It also dose dependently inhibited HUVEC adhesion to immobilized extracellular matrices fibronectin, collagen I and vitronectin with respective IC(50) values of approximately 0.6, 0.3 and 0.1 microM. Acurhagin-C prevented migration and invasion of HUVEC through vitronectin- and Matrigel-coated barriers respectively. Furthermore, acurhagin-C attenuated fibroblast growth factor-2-primed angiogenesis both in vitro and in vivo, and specifically blocked the binding of anti-alphavbeta3 monoclonal antibody 23C6 to HUVEC in an ECD-dependent manner. However, purified alphavbeta3 also dose-dependently bound to immobilized acurhagin and acurhagin-C with a saturable pattern. Interference with integrin alphavbeta3-mediated functions and promotion of caspase-3 activation by acurhagin C affected morphology of HUVEC and induced apoptosis. CONCLUSIONS AND IMPLICATIONS: Acurhagin-C elicited endothelial anoikis via disruption of alphavbeta3/focal adhesion kinase/phosphatidylinositol 3-kinase/Akt survival cascade and subsequent initiation of the procaspase-3 apoptotic signalling pathway. PMID- 20590626 TI - 2,3',4,4',5'-Pentamethoxy-trans-stilbene, a resveratrol derivative, inhibits colitis-associated colorectal carcinogenesis in mice. AB - BACKGROUND AND PURPOSE: Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3',4,4',5'-pentamethoxy-trans stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti-proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis-associated colon carcinogenesis. EXPERIMENTAL APPROACH: Seven-week-old Balb/c mice were injected i.p. with 10 mg.kg(-1) azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice. KEY RESULTS: Intragastric administration of PMS (25, 50 mg.kg(-1) body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg.kg(-1) inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of beta-catenin and down regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of beta-catenin. CONCLUSIONS AND IMPLICATIONS: PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis-associated colon cancer in humans. PMID- 20590627 TI - Sublethal concentrations of the platinum(II) complex [Pt(O,O'-acac)(gamma acac)(DMS)] alter the motility and induce anoikis in MCF-7 cells. AB - BACKGROUND AND PURPOSE: We showed previously that a new Pt(II) complex ([Pt(O,O' acac)(gamma-acac)(DMS)]) exerted high and fast apoptotic processes in MCF-7 cells. The objective of this study was to investigate the hypothesis that [Pt(O,O'-acac)(gamma-acac)(DMS)] is also able to exert anoikis and alter the migration ability of MCF-7 cells, and to show some of the signalling events leading to these alterations. EXPERIMENTAL APPROACH: Cells were treated with sublethal doses of [Pt(O,O'-acac)(gamma-acac)(DMS)], and the efficiency of colony initiation and anchorage-independent growth was assayed; cell migration was examined by in vitro culture wounding assay. Gelatin zymography for MMP-2 and -9 activities, Western blottings of MMPs, MAPKs, Src, PKC-epsilon and FAK, after [Pt(O,O'-acac)(gamma-acac)(DMS)] treatment, were also performed. KEY RESULTS: Sub cytotoxic drug concentrations decreased the: (i) anchorage-dependent and independent growth; (ii) migration ability; and (iii) expression and activity of MMP-2 and MMP-9. [Pt(O,O'-acac)(gamma-acac)(DMS)] provoked the generation of reactive oxygen species (ROS), and the activation of p38MAPK, Src and PKC epsilon. p38MAPK phosphorylation, cell anoikis and migration due to [Pt(O,O' acac)(gamma-acac)(DMS)] were blocked by PKC-epsilon inhibition. Furthermore, Src inhibition blocked the [Pt(O,O'-acac)(gamma-acac)(DMS)]-provoked activation of PKC-epsilon, while ROS generation blockage inhibited the activation of Src, and also the decrement of phosphorylated FAK observed in detached [Pt(O,O' acac)(gamma-acac)(DMS)]-treated cells. CONCLUSIONS AND IMPLICATIONS: Sublethal concentrations of [Pt(O,O'-acac)(gamma-acac)(DMS)] induced anoikis and prevented events leading to metastasis via alterations in cell migration, anchorage independency, stromal interactions and MMP activity. Hence, [Pt(O,O'-acac)(gamma acac)(DMS)] may be a promising therapeutic agent for preventing growth and metastasis of breast cancer. PMID- 20590628 TI - Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction. AB - BACKGROUND AND PURPOSE: Post-transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T-cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE-2, AGE-3, AGE-4 and AGE-5), only AGE-2 and AGE-3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR. EXPERIMENTAL APPROACH: Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM-1, B7.1, B7.2 and CD40. Production of the cytokine interferon-gamma, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [(3)H]-thymidine uptake. KEY RESULTS: Histamine concentration dependently inhibited the action of AGE-2 and AGE-3. The actions of histamine were antagonized by an H(2)-receptor antagonist, famotidine, and mimicked by H(2)/H(4)-receptor agonists, dimaprit and 4-methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin. CONCLUSIONS AND IMPLICATIONS: Histamine down-regulated AGE-2- and AGE-3-induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H(2) receptors and the cAMP/PKA pathway. PMID- 20590629 TI - AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist. AB - BACKGROUND AND PURPOSE: Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The current work describes the in vitro pharmacological characteristics of AF-353, a novel, orally bioavailable, highly potent and selective P2X3/P2X2/3 receptor antagonist. EXPERIMENTAL APPROACH: The antagonistic potencies (pIC(50)) of AF-353 for rat and human P2X3 and human P2X2/3 receptors were determined using methods of radioligand binding, intracellular calcium flux and whole cell voltage-clamp electrophysiology. KEY RESULTS: The pIC(50) estimates for these receptors ranged from 7.3 to 8.5, while concentrations 300-fold higher had little or no effect on other P2X channels or on an assortment of receptors, enzymes and transporter proteins. In contrast to A 317491 and TNP-ATP, competition binding and intracellular calcium flux experiments suggested that AF-353 inhibits activation by ATP in a non-competitive fashion. Favourable pharmacokinetic parameters were observed in rat, with good oral bioavailability (%F = 32.9), reasonable half-life (t(1/2) = 1.63 h) and plasma-free fraction (98.2% protein bound). CONCLUSIONS AND IMPLICATIONS: The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders. PMID- 20590630 TI - Effects of combination therapy with montelukast and carbocysteine in allergen induced airway hyperresponsiveness and airway inflammation. AB - BACKGROUND AND PURPOSE: Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S carbocysteine also exhibits anti-inflammatory properties. EXPERIMENTAL APPROACH: Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production. KEY RESULTS: Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid. CONCLUSIONS AND IMPLICATIONS: The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action. PMID- 20590631 TI - The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits. AB - BACKGROUND AND PURPOSE: The formation of reactive oxygen species (ROS) is increased in heart failure (HF). However, the causal and mechanistic relationship of ROS formation with contractile dysfunction is not clear in detail. Therefore, ROS formation, myofibrillar protein oxidation and p38 MAP kinase activation were related to contractile function in failing rabbit hearts. EXPERIMENTAL APPROACH AND KEY RESULTS: Three weeks of rapid left ventricular (LV) pacing reduced LV shortening fraction (SF, echocardiography) from 32 +/- 1% to 13 +/- 1%. ROS formation, as assessed by dihydroethidine staining, increased by 36 +/- 8% and was associated with increased tropomyosin oxidation, as reflected by dimer formation (dimer to monomer ratio increased 2.28 +/- 0.66-fold in HF vs. sham, P < 0.05). Apoptosis (TdT-mediated dUTP nick end labelling staining) increased more than 12-fold after 3 weeks of pacing when a significant increase in the phosphorylation of p38 MAP kinase and HSP27 was detected (Western blotting). Vitamins C and E abolished the increases in ROS formation and tropomyosin oxidation along with an improvement of LVSF (19 +/- 1%, P < 0.05 vs. untreated HF) and prevention of apoptosis, but without modifying p38 MAP kinase activation. Inhibition of p38 MAP kinase by SB281832 counteracted ROS formation, tropomyosin oxidation and contractile failure, without affecting apoptosis. CONCLUSIONS AND IMPLICATIONS: Thus, p38 MAP kinase activation appears to be upstream rather than downstream of ROS, which impacts on LV function through myofibrillar oxidation. p38 MAP kinase inhibition is a potential target to prevent or treat HF. PMID- 20590632 TI - A series of structurally novel heterotricyclic alpha-amino-3-hydroxyl-5-methyl-4 isoxazole-propionate receptor-selective antagonists. AB - BACKGROUND AND PURPOSE: A new class of heterotricyclic glutamate analogues recently was generated by incorporating structural elements of two excitotoxic marine compounds, kainic acid and neodysiherbaine A. Rather than acting as convulsants, several of these 'IKM' compounds markedly depressed CNS activity in mice. Here, we characterize the pharmacological profile of the series with a focus on the most potent of these molecules, IKM-159. EXPERIMENTAL APPROACH: The pharmacological activity and specificity of IKM compounds were characterized using whole-cell patch clamp recording from neurons and heterologous receptor expression systems, in combination with radioligand binding techniques. KEY RESULTS: The majority of the IKM compounds tested reduced excitatory synaptic transmission in neuronal cultures, and IKM-159 inhibited synaptic currents from CA1 pyramidal neurons in hippocampal slices. IKM-159 inhibited glutamate-evoked whole-cell currents from recombinant GluA2- and GluA4-containing alpha-amino-3 hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors most potently, whereas kainate and NMDA receptor currents were not reduced by IKM-159. Antagonism of steady-state currents was agonist concentration dependent, suggesting that its mechanism of action was competitive, although it paradoxically did not displace [(3)H]-AMPA from receptor binding sites. IKM-159 reduced spontaneous action potential firing in both cultured hippocampal neurons in control conditions and during hyperactive states in an in vitro model of status epilepticus. CONCLUSIONS AND IMPLICATIONS: IKM-159 is an AMPA receptor-selective antagonist. IKM-159 and related nitrogen heterocycles represent structurally novel AMPA receptor antagonists with accessible synthetic pathways and potentially unique pharmacology, which could be of use in exploring the role of specific populations of receptors in neurophysiological and neuropathological processes. PMID- 20590634 TI - Increased morphine analgesia and reduced side effects in mice lacking the tac1 gene. AB - BACKGROUND AND PURPOSE: Although morphine is a very effective analgesic, its narrow therapeutic index and severe side effects limit its therapeutic use. Previous studies indicated that the pharmacological responses of opioids are modulated by genetic and pharmacological invalidation of tachykinin receptors. Here we address the role of substance P and neurokinin A, which are both encoded by the tachykinin 1 (tac1) gene, as modulators of opioid effects. EXPERIMENTAL APPROACH: The analgesic and side effect potential of morphine was compared between wild-type and tac1 null mutant mice. KEY RESULTS: Morphine was a more potent analgesic in tac1 null mutant mice, that is, in the absence of substance P/neurokinin A signalling. Interestingly, the most serious side effect of acute morphine, that is respiratory depression, was reduced in tac1(-/-) animals. Comparing the addictive potential of morphine in wild-type and knockout animals we found that morphine preference was similar between the genotypes. However, the aversive effect of withdrawal precipitated by naloxone in morphine-dependent animals was significantly reduced in tac1 knockout mice. Behavioural sensitization, the underlying mechanism of addiction, was also significantly lower in tac1(-/-) mice. CONCLUSION AND IMPLICATIONS: The analgesic potential of morphine was increased in tac1 knockout mice. In contrast, both the ventilatory suppressing effect and the addictive potential of morphine were reduced. These results suggest that reducing activity of the tachykinin system may be a possible strategy to improve the pharmacological potential of morphine. PMID- 20590633 TI - Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels. AB - BACKGROUND AND PURPOSE: Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker. EXPERIMENTAL APPROACH: One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-II(o) of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week. KEY RESULTS: Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg.kg(-1)) or the TRPA1 channel blocker HC-030031 (300 mg.kg(-1)) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031. CONCLUSIONS AND IMPLICATIONS: Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions. PMID- 20590635 TI - Differences in the expression of endogenous efflux transporters in MDR1 transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport. AB - BACKGROUND AND PURPOSE: P-glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin-Darby canine kidney (MDCK) II and LLC-PK1, transfected with human MDR1 (ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport in MDR1-transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport. EXPERIMENTAL APPROACH: Using quantitative real-time RT-PCR, we determined the expression of endogenous Mdr1 mRNA and other efflux transporters in wildtype and MDR1-transfected MDCK-II and LLC cells. Transcellular transport was measured with the test substrate vinblastine. KEY RESULTS: In MDR1-transfected MDCK cells, expression of endogenous (canine) Mdr1 and Mrp2 (Abcc2) mRNA was markedly lower than in wildtype cells, whereas MDR1-transfected LLC cells exhibited comparable Mdr1 but strikingly higher Mrp2 mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport in MDR1-transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells. CONCLUSIONS AND IMPLICATIONS: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias for in vitro studies on Pgp-mediated drug transport. PMID- 20590636 TI - The transient receptor potential channel antagonist SKF96365 is a potent blocker of low-voltage-activated T-type calcium channels. AB - BACKGROUND AND PURPOSE: SKF96365 (SKF), originally identified as a blocker of receptor-mediated calcium entry, is widely used diagnostically, as a blocker of transient receptor potential canonical type (TRPC) channels. While SKF has been used as a tool to define the functional roles of TRPC channels in various cell and tissue types, there are notable overlapping physiological and pathophysiological associations between TRPC channels and low-voltage-activated (LVA) T-type calcium channels. The activity of SKF against T-type Ca channels has not been previously explored, and here we systematically investigated the effects of SKF on recombinant and native voltage-gated Ca channel-mediated currents. EXPERIMENTAL APPROACH: Effects of SKF on recombinant Ca channels were studied under whole-cell patch clamp conditions after expression in HEK293 cells. The effect of SKF on cerebellar Purkinje cells (PCs) expressing native T-type Ca channels was also assessed. KEY RESULTS: SKF blocked recombinant Ca channels, representative of each of the three main molecular genetic classes (Ca(V)1, Ca(V)2 and Ca(V)3) at concentrations typically utilized to assay TRPC function (10 microM). Particularly, human Ca(V)3.1 T-type Ca channels were more potently inhibited by SKF (IC(50) approximately 560 nM) in our experiments than previously reported for similarly expressed TRPC channels. SKF also inhibited native Ca(V)3.1 T-type currents in a rat cerebellar PC slice preparation. CONCLUSIONS AND IMPLICATIONS: SKF was a potent blocker of LVA T-type Ca channels. We suggest caution in the interpretation of results using SKF alone as a diagnostic agent for TRPC activity in native tissues. PMID- 20590637 TI - Differential sensitivity of basal and acetylcholine-induced activity of nitric oxide to blockade by asymmetric dimethylarginine in the rat aorta. AB - BACKGROUND AND PURPOSE: Previous work has shown that N(G)-monomethyl-l-arginine (l-NMMA) paradoxically inhibits basal, but not ACh-stimulated activity of nitric oxide in rat aorta. The aim of this study was to determine if the endogenously produced agent, asymmetric N(G), N(G)-dimethyl-l-arginine (ADMA), also exhibits this unusual selective blocking action. EXPERIMENTAL APPROACH: The effect of ADMA on basal nitric oxide activity was assessed by examining its ability to enhance phenylephrine (PE)-induced tone in endothelium-containing rings. Its effect on ACh-induced relaxation was assessed both in conditions where ADMA greatly enhanced PE tone and where tone was carefully matched with control tissues at a range of different levels. KEY RESULTS: ADMA (100 microM) potentiated PE-induced contraction, consistent with inhibition of basal nitric oxide activity. Higher concentrations (300-1000 microM) had no greater effect. Although ADMA (100 microM) also appeared to block ACh-induced relaxation when it enhanced PE tone to maximal levels, virtually no block was seen at intermediate levels of tone in the presence of ADMA. Even ADMA at 1000 microM had no effect on the maximal relaxation to ACh, although it produced a small (two- to threefold) reduction in sensitivity. ADMA and l-NMMA, like l-arginine (all at 1000 microM), protected ACh induced relaxation against blockade by l-NAME (30 microM). CONCLUSIONS AND IMPLICATIONS: In the rat aorta, ADMA, like l-NMMA, blocks basal activity of nitric oxide, but has little effect on that stimulated by ACh. Further studies are required to explain these seemingly anomalous actions of ADMA and l-NMMA. PMID- 20590638 TI - Haemin-enhanced expression of haem oxygenase-1 stabilizes erythrocyte-induced vulnerable atherosclerotic plaques. AB - BACKGROUND AND PURPOSE: Previous studies demonstrated that intraplaque haemorrhage increased the contents of cholesterol and oxidants in atherosclerotic plaques. The present study was aimed to test the hypothesis that enhanced expression of haem oxygenase-1 (HO-1) may stabilize vulnerable plaques. EXPERIMENTAL APPROACH: Intravascular ultrasound (IVUS) was performed to identify three similar abdominal aortic plaques in each of 58 fat-fed New Zealand rabbits after aortic balloon injury. With the guidance of IVUS, 50 microL autologous erythrocytes (RBC) or normal saline (NS) were injected from adventitia into two of the pre-selected plaques, respectively, whereas the third plaque served as a blank control. All rabbits were randomly divided into two groups, receiving intraperitoneal injection of haemin and saline respectively. KEY RESULTS: Compared with NS or control plaques, RBC plaques had more macrophage infiltration and lipid content, thinner plaque fibrous cap, and higher expression of inflammatory factors and incidence of plaque rupture. RBC plaques in the haemin group had about a 50% lower incidence of plaque rupture than those in the control group. CONCLUSIONS AND IMPLICATIONS: Haem oxygenase-1 may eliminate haem or other oxidants, exert unexpected anti-oxidative and anti-inflammatory effects and serve as a promising approach to the direct inhibition of erythrocyte-induced plaque instability. PMID- 20590639 TI - Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles. AB - BACKGROUND AND PURPOSE: Small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance calcium-activated potassium channels are involved in regulation of vascular tone and blood pressure. The present study investigated whether NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) and CyPPA (cyclohexyl-[2 (3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine), which are selective openers of SK(Ca) and IK(Ca) channels and of SK(Ca)2 and SK(Ca)3 channels, respectively, enhance endothelium-dependent vasodilatation in porcine retinal arterioles. EXPERIMENTAL APPROACH: In porcine retinal arterioles, SK(Ca)3 and IK(Ca) protein localization was examined by immunolabelling. Endothelial cell calcium was measured by fluorescence imaging. For functional studies, arterioles with internal diameters of 116 +/- 2 microm (n = 276) were mounted in microvascular myographs for isometric tension recordings. KEY RESULTS: SK(Ca)3 and IK(Ca) protein was localized in the endothelium. Bradykinin, but not NS309 or CyPPA increased endothelial cell calcium. Pre-incubation with NS309 or CyPPA enhanced bradykinin relaxation without changing endothelial cell calcium. This enhanced relaxation was abolished by blocking SK(Ca) channels with apamin. In the presence of NS309 or CyPPA, mainly inhibition of NO synthase with asymmetric dimethylarginine, but also inhibition of cyclooxygenase with indomethacin, reduced bradykinin relaxation. Bradykinin relaxation was completely abolished by NO synthase and cyclooxygenase inhibition together with a NO scavenger, oxyhaemoglobin. CONCLUSIONS AND IMPLICATIONS: In porcine retinal arterioles, bradykinin increases endothelial cell calcium leading to activation of SK(Ca) and IK(Ca) channels. Without altering endothelial cell calcium, NS309 and CyPPA open SK(Ca) channels that enhance NO-mediated bradykinin relaxations. These results imply that opening SK(Ca) channels improves endothelium-dependent relaxation and makes this channel a potential target for treatments aimed at restoring retinal blood flow. PMID- 20590640 TI - Trace amines depress D(2)-autoreceptor-mediated responses on midbrain dopaminergic cells. AB - BACKGROUND AND PURPOSE: Although trace amines (TAs) are historically considered 'false neurotransmitters' on the basis of their ability to induce catecholamine release, there is evidence that they directly affect neuronal activity via TA receptors, ligand-gated receptor channels and/or sigma receptors. Here, we have investigated the effects of two TAs, tyramine (TYR) and beta-phenylethylamine (beta-PEA), on electrophysiological responses of substantia nigra pars compacta (SNpc) dopaminergic cells to the D(2) receptor agonist, quinpirole. EXPERIMENTAL APPROACH: Electrophysiological recordings of D(2) receptor-activated G-protein gated inward rectifier K(+) channel (GIRK) currents were performed on dopaminergic cells from midbrain slices of mice and on Xenopus oocytes expressing D(2) receptors and GIRK channels. KEY RESULTS: TYR and beta-PEA reversibly reduced D(2) receptor-activated GIRK currents in a concentration-dependent manner on SNpc neurones. The inhibitory effect of TAs was still present in transgenic mice with genetically deleted TA(1) receptors and they could not be reproduced by the selective TA(1) agonist, o-phenyl-3-iodotyramine (O-PIT). Pretreatment with antagonists of sigma1 and sigma2 receptors did not block TA-induced effects. In GTPgammaS-loaded neurones, the irreversibly-activated GIRK-current was still reversibly reduced by beta-PEA. Moreover, beta-PEA did not affect basal or dopamine-evoked GIRK-currents in Xenopus oocytes. CONCLUSIONS AND IMPLICATIONS: TAs reduced dopamine-induced responses on SNpc neurones by acting at sites different from TA(1), sigma-receptors, D(2) receptors or GIRK channels. Although their precise mechanism of action remains to be identified, TAs, by antagonizing the inhibitory effects of dopamine, may render dopaminergic neurones less sensitive to autoreceptor feedback inhibition and hence enhance their sensitivity to stimulation. PMID- 20590641 TI - Molecular determinants of state-dependent block of voltage-gated sodium channels by pilsicainide. AB - BACKGROUND AND PURPOSE: Pilsicainide, an anti-arrhythmic drug used in Japan, is described as a pure sodium channel blocker. We examined the mechanisms by which it is able to block open channels, because these properties may be especially useful to reduce hyperexcitability in pathologies characterized by abnormal sodium channel opening. EXPERIMENTAL APPROACH: The effects of pilsicainide on various heterologously expressed human sodium channel subtypes and mutants were investigated using the patch clamp technique. KEY RESULTS: Pilsicainide exhibited tonic and use-dependent effects comparable to those of mexiletine and flecainide on hNav1.4 channels. These use-dependent effects were abolished in the mutations F1586C and Y1593C within segment 6 of domain IV, suggesting that the interaction of pilsicainide with these residues is critical for its local anaesthetic action. Its affinity constants for closed channels (K(R)) and channels inactivated from the closed state (K(I)) were high, suggesting that its use-dependent block (UDB) requires the channel to be open for it to reach a high-affinity blocking site. Accordingly, basic pH, which slightly increased the proportion of neutral drug, dramatically decreased K(R) and K(I) values. Effects of pilsicainide were similar on skeletal muscle hNav1.4, brain hNav1.1 and heart hNav1.5 channels. The myotonic R1448C and G1306E hNav1.4 mutants were more and less sensitive to pilsicainide, respectively, due to mutation-induced gating modifications. CONCLUSIONS AND IMPLICATIONS: Although therapeutic concentrations of pilsicainide may have little effect on resting and closed-state inactivated channels, it induces a strong UDB due to channel opening, rendering the drug ideally suited for inhibition of high-frequency action potential firing. PMID- 20590642 TI - Investigating the interaction of McN-A-343 with the M muscarinic receptor using its nitrogen mustard derivative and ACh mustard. AB - BACKGROUND AND PURPOSE: We investigated how McN-A-343 inhibited the alkylation of the M(1) muscarinic receptor by its nitrogen mustard derivative and that of ACh to identify whether it interacts allosterically or orthosterically. EXPERIMENTAL APPROACH: We incubated the M(1) muscarinic receptor expressed in Chinese hamster ovary cells with ACh mustard for various periods of time in the presence of McN-A 343 or known allosteric and orthosteric ligands. After stopping the reaction and removing unreacted ligands, unalkylated receptors were measured using [(3)H]N methylscopolamine. Analogous experiments were done using a nitrogen mustard analog of McN-A-343. Affinity constants, cooperativity values for allosteric interactions and rate constants for receptor alkylation were estimated using a mathematical model. KEY RESULTS: The kinetics of receptor alkylation by the nitrogen mustard derivatives of ACh and McN-A-343 were consistent with a two-step model in which the aziridinium ion rapidly forms a reversible receptor complex, which converts to a covalent complex at a slower rate. The inhibition of receptor alkylation by acetycholine, N-methylscopolamine and McN-A-343 was consistent with competitive inhibition, whereas that caused by gallamine was consistent with allosterism. Affinity constants estimated from alkylation kinetics agreed with those measured by displacement of [(3)H]N-methylscopolamine binding. CONCLUSIONS AND IMPLICATIONS: Our results suggest that McN-A-343 and its nitrogen mustard derivative interact competitively with ACh and N-methylscopolamine at the orthosteric site on the M(1) muscarinic receptor. Measuring how drugs modulate the kinetics of receptor alkylation by an irreversible ligand is a powerful approach for distinguishing between negative allosteric modulators and competitive inhibitors. PMID- 20590643 TI - Co-administration of ibuprofen and nitric oxide is an effective experimental therapy for muscular dystrophy, with immediate applicability to humans. AB - BACKGROUND AND PURPOSE: Current therapies for muscular dystrophy are based on corticosteroids. Significant side effects associated with these therapies have prompted several studies aimed at identifying possible alternative strategies. As inflammation and defects of nitric oxide (NO) generation are key pathogenic events in muscular dystrophies, we have studied the effects of combining the NO donor isosorbide dinitrate (ISDN) and the non-steroidal anti-inflammatory drug ibuprofen. EXPERIMENTAL APPROACH: alpha-Sarcoglycan-null mice were treated for up to 8 months with ISDN (30 mg.kg(-1)) plus ibuprofen (50 mg.kg(-1)) administered daily in the diet. Effects of ISDN and ibuprofen alone were assessed in parallel. Drug effects on animal motility and muscle function, muscle damage, inflammatory infiltrates and cytokine levels, as well as muscle regeneration including assessment of endogenous stem cell pool, were measured at selected time points. KEY RESULTS: Combination of ibuprofen and ISDN stimulated regeneration capacity, of myogenic precursor cells, reduced muscle necrotic damage and inflammation. Muscle function in terms of free voluntary movement and resistance to exercise was maintained throughout the time window analysed. The effects of ISDN and ibuprofen administered separately were transient and significantly lower than those induced by their combination. CONCLUSIONS AND IMPLICATIONS: Co administration of NO and ibuprofen provided synergistic beneficial effects in a mouse model of muscular dystrophy, leading to an effective therapy. Our results open the possibility of immediate clinical testing of a combination of ISDN and ibuprofen in dystrophic patients, as both components are approved for use in humans, with a good safety profile. PMID- 20590644 TI - Beta(2)-adrenoceptor agonist clenbuterol reduces infarct size and myocardial apoptosis after myocardial ischaemia/reperfusion in anaesthetized rats. AB - BACKGROUND AND PURPOSE: Considerable evidence indicates that the beta(2) adrenoceptor agonist clenbuterol decreases apoptosis in a rodent model of ischaemic cardiomyopathy. In this study, we investigated the effects of clenbuterol on infarct size caused by myocardial ischaemia/reperfusion (I/R) in anaesthetized rats. EXPERIMENTAL APPROACH: Rats were randomly assigned to the following groups: (i) sham (ii) I/R (iii) clenbuterol + I/R (iv) ICI 118551 + clenbuterol + I/R (v) metoprolol + clenbuterol + I/R (vi) metoprolol + I/R (vii) pertussis toxin + clenbuterol + I/R. Under anaesthesia, left anterior descending coronary artery was occluded for 30 min followed by reperfusion for 2 h. KEY RESULTS: Compared with the control I/R group,the clenbuterol (0.5 mg.kg(-1), i.p.) group had reduced infarct size, improved diastolic function and sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) activity, increased superoxide dismutase activity, and decreased malondialdehyde (MDA) level and LDH, CK release. Clenbuterol increased the phosphorylation of ERK1/2, which resulted in inhibition of myocardial apoptosis as indicated by the reduction of terminal deoxynucleotidyltransferase end labelling-positive staining, Bax/Bcl-2 mRNA and caspase-3 protein expression. The G(i)-protein inhibitor pertussis toxin blocked the clenbuterol-induced improvement in cardiac function and infarct size. Pretreatment with ICI 118551(a selective beta(2)-adrenoceptor antagonist) inhibited the effects of clenbuterol mentioned above. The beta(1)-adrenoceptor agonist metoprolol had similar effects to clenbuterol but failed to reduce MDA and improve SERCA activity. When administered together, metoprolol and clenbuterol did not induce synergistic effects. CONCLUSIONS AND IMPLICATIONS: Clenbuterol pretreatment provides significant cardioprotection against ischaemia/reperfusion injury and this is mediated by the beta(2)-adrenoceptor G(i)-protein signalling. A combination of the beta(2)-adrenoceptor agonist clenbuterol and the beta(1)-antagonist metoprolol did not lead to a synergistic anti-apoptotic effect. PMID- 20590646 TI - A life in new drug research. PMID- 20590647 TI - Sir James Black (1924-2010). PMID- 20590649 TI - Comparison of some properties of pronethalol and propranolol. 1965. PMID- 20590650 TI - James Whyte Black. 14 June 1924-22 March 2010. PMID- 20590652 TI - An analysis of the depressor responses to histamine in the cat and dog: involvement of both H1- and H2-receptors. 1975. PMID- 20590653 TI - Sir James Black (1924-2010) reflections. PMID- 20590655 TI - The pharmacology of cimetidine, a new histamine H2-receptor antagonist. 1975. PMID- 20590656 TI - An operational model of pharmacological agonism: the effect of E/[A] curve shape on agonist dissociation constant estimation. 1985. PMID- 20590658 TI - MEK/ERK and p38 MAPK regulate chondrogenesis of rat bone marrow mesenchymal stem cells through delicate interaction with TGF-beta1/Smads pathway. AB - OBJECTIVES: This study was carried out to reveal functions and mechanisms of MEK/ERK and p38 pathways in chondrogenesis of rat bone marrow mesenchymal stem cells (BMSCs), and to investigate further any interactions between the mitogen activated protein kinase (MAPK) and transforming growth factor-beta1 (TGF beta1)/Smads pathway in the process. MATERIALS AND METHODS: Chondrogenic differentiation of rat BMSCs was initiated in micromass culture, in the presence of TGF-beta1, for 2 weeks. ERK1/2 and p38 kinase activities were investigated by Western Blot analysis. Specific MAPK inhibitors PD98059 and SB20350 were employed to investigate regulatory effects of MEK/ERK and p38 signals on gene expression of chondrocyte-specific markers, and TGF-beta1 downstream pathways of Smad2/3. RESULTS: ERK1/2 was phosphorylated in a rapid but transient manner, whereas p38 was activated in a slow and sustained way. The two MAPK subtypes played opposing roles in mediating transcription of cartilage-specific genes for Col2alpha and aggrecan. TGF-beta1-stimulated gene expression of chondrogenic regulators, Sox9, Runx2 and Ihh, was also affected by activity of PD98059 and SB203580, to different degrees. However, influences of MAPK inhibitors on gene expression were relatively minor when not treated with TGF-beta1. In addition, gene transcription of Smad2/3 was significantly upregulated by TGF-beta1, but was regulated more subtly by treatment with MAPK inhibitors. CONCLUSIONS: MAPK subtypes seemed to regulate chondrogenesis with a delicate balance, interacting with the TGF beta1/Smads signalling pathway. PMID- 20590659 TI - Oscillations in growth of multicellular tumour spheroids: a revisited quantitative analysis. AB - OBJECTIVES: Multicellular tumour spheroids (MTS) provide an important tool for study of the microscopic properties of solid tumours and their responses to therapy. Thus, observation of large-scale volume oscillations in MTS, reported several years ago by two independent groups (1,2), in our opinion represent a remarkable discovery, particularly if this could promote careful investigation of the possible occurrence of volume oscillations of tumours 'in vivo'. MATERIALS AND METHODS: Because of high background noise, quantitative analysis of properties of observed oscillations has not been possible in previous studies. Such an analysis can be now performed, thanks to a recently proposed approach, based on formalism of phenomenological universalities (PUN). RESULTS: Results have provided unambiguous confirmation of the existence of MTS volume oscillations, and quantitative evaluation of their properties, for two tumour cell lines. Proof is based not only on quality of fitting of the experimental datasets, but also on determination of well-defined values of frequency and amplitude of the oscillations for each line investigated, which would not be consistent with random fluctuation. CONCLUSIONS: Biological mechanisms, which can be directly responsible for observed oscillations, are proposed, which relates also to recent work on related topics. Further investigations, both at experimental and at modelling levels, are also suggested. Finally, from a methodological point of view, results obtained represent further confirmation of applicability and usefulness of the PUN approach. PMID- 20590657 TI - Elucidation of XA21-mediated innate immunity. AB - In the early 1970s, the Xa21 gene from the wild rice species Oryza longistaminata drew attention of rice breeders because of its broad-spectrum resistance to diverse strains of a serious bacterial disease of rice in Asia and Africa, called 'bacterial blight disease', caused by the Gram-negative bacterium, Xanthomonas oryzae pv. oryzae (Xoo). In 1995, we isolated the gene controlling this resistance and in 2009 demonstrated that XA21 recognizes a highly conserved peptide, called 'Ax21' (activator of XA21-mediated immunity). Tyrosine sulfation of Ax21 is required for recognition by rice XA21. A decade of genetic, molecular and biochemical studies have uncovered key components of the XA21-mediated signalling cascade. Ax21 recognition by XA21 at the cell surface induces phosphorylation-mediated events, which are predicted to alter subcellular localization and/or DNA-binding activity of a WRKY family of transcription factors. Because XA21 is representative of the large number of predicted pattern recognition receptors (PRRs) in rice (n = 328), Arabidopsis (n = 35) and other plant species, further characterization of XA21-mediated signalling pathways will contribute to elucidation of these important defence responses. PMID- 20590660 TI - Curcumin disrupts meiotic and mitotic divisions via spindle impairment and inhibition of CDK1 activity. AB - OBJECTIVES: Curcumin, a natural compound, is a potent anti-cancer agent, which inhibits cell division and/or induces cell death. It is believed that normal cells are less sensitive to curcumin than malignant cells; however, the mechanism(s) responsible for curcumin's effect on normal cells are poorly understood. The aim of this study was to verify the hypothesis that curcumin affects normal cell division by influencing microtubule stability, using mouse oocyte and early embryo model systems. MATERIALS AND METHODS: Maturating mouse oocytes and two-cell embryos were treated with different concentrations of curcumin (10-50 microm), and meiotic resumption and mitotic cleavage were analysed. Spindle and chromatin structure were visualized using confocal microscopy. In addition, acetylation and in vitro polymerization of tubulin, in the presence of curcumin, were investigated and the damage to double-stranded DNA was studied using gammaH2A.X. CDK1 activity was measured. RESULTS AND CONCLUSIONS: We have shown for the first time, that curcumin, in a dose-dependent manner, delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by causing disruption of spindle structure and does not induce DNA damage. Our analysis indicated that curcumin affects CDK1 kinase activity but does not directly affect microtubule polymerization and tubulin acetylation. As our study showed that curcumin impairs generative and somatic cell division, its future clinical use or of its derivatives with improved bioavailability after oral administration, should take into consideration the possibility of extensive side-effects on normal cells. PMID- 20590661 TI - p53-dependent G(1) arrest in 1st or 2nd cell cycle may protect human cancer cells from cell death after treatment with ionizing radiation and Chk1 inhibitors. AB - OBJECTIVES: This study was performed to explore the strategy of combining Chk1 inhibitors with ionizing radiation (IR) to selectively target p53-deficient cancer cells. MATERIALS AND METHODS: Survival and cell cycle progression were measured in response to IR and the Chk1 inhibitors, UCN-01 and CEP-3891, in colon carcinoma HCT116 p53+/+ and p53-/- cells, and in osteosarcoma U2OS-VP16 cells with conditional expression of dominant-negative p53 (p53DD). RESULTS: Clonogenic survival was selectively reduced in HCT116 p53-/- compared to p53+/+ cells after treatment with UCN-01 and IR, and HCT116 p53+/+ cells also displayed strong p53 dependent G(1) arrest in the 1st cell cycle after IR. In contrast, clonogenic survival was affected similarly in U2OS-VP16 cells with and without expression of p53DD. However, death of U2OS-VP16 cells was p53 dependent as assessed by cell viability assay at 72 h, and this was associated with p53-dependent G(1) arrest in the 2nd cell cycle after treatment. Notably, HCT116 cells were overall more resistant than U2OS cells to cytotoxic effects of Chk1 inhibitors. CONCLUSION: Our results suggest that p53-dependent G(1) arrest in both 1st and 2nd cell cycles may protect human cancer cells from cell death after treatment with IR and Chk1 inhibitors. However, a challenge for future clinical use will be that different cancers display different intrinsic sensitivity to such inhibitors. PMID- 20590662 TI - Spontaneous immortalization of neural crest-derived corneal progenitor cells after chromosomal aberration. AB - OBJECTIVES: In a previous study, we have reported the existence of neural crest derived stem cell-like cells originating from the corneal limbus of juvenile mice (termed murine corneal cells, MCCs). To yield a sufficient number of MCCs, for example, for cell-therapy approaches, here we have investigated MCCs' ability for extensive proliferation, and we have evaluated their stem cell qualities and genetic stability after large-scale culture. MATERIALS AND METHODS: MCCs were established from corneal limbal tissue of juvenile mice. To determine their cell proliferation and self-renewing potential, MTT tests and an estimation of colony forming unit efficiency were carried out. Multipotency of cell differentiation was examined by applying adipogenic and osteogenic differentiation protocols. Moreover, karyotyping was performed and expression of stem cell markers and cell cycle-associated genes was analysed. RESULTS: MCCs, as primary cells, could be cultured for more than 60 passages. We observed increased cell proliferation and high number of colony forming units (CFUs) after extensive culture. Interestingly, there were no changes in expression of MCC markers. Furthermore, cell differentiation potentials remained comparable with MCCs at early passages. However, karyotyping revealed numeric chromosomal aberrations at higher passages. Moreover, tumour suppressor genes such as p16 and p21 were found to be down regulated after large-scale cell culture. CONCLUSIONS: MCCs immortalize spontaneously after extensive cell culture, but still demonstrate stem cell-like qualities. PMID- 20590663 TI - Expression phenotype changes of EBV-transformed lymphoblastoid cell lines during long-term subculture and its clinical significance. AB - OBJECTIVES: The EBV-transformed lymphoblastoid cell line (LCL) is a useful resource for population-based human genetic and pharmacogenetic studies. The principal objective here was to assess expression phenotype changes during long term subculture of LCLs, and its clinical significance. MATERIALS AND METHODS: We searched for genes that were differentially expressed in 17 LCLs at late (p161) passage compared to early passage (p4) using microarray assay, then validated them by real-time RT-PCR analysis. In addition, we estimated correlations between expression phenotypes of 20 LCL strains at early passage and 23 quantitative clinical traits from blood donors of particular LCL strains. RESULTS: Transcript sequences of 16 genes including nuclear factor-kappaB (NF-kappaB) pathway-related genes (such as PTPN13, HERC5 and miR-146a) and carcinogenesis-related genes (such as XAF1, TCL1A, PTPN13, CD38 and miR-146a) were differentially expressed (>2-fold change) in at least 15 of the 17 LCL strains. In particular, TC2N, FCRL5, CD180, CD38 and miR-146a were downregulated in all 17 of the evaluated LCL strains. In addition, we identified clinical trait-associated expression phenotypes in LCLs. CONCLUSION: Our results showed that LCLs acquired expression phenotype changes involving expression of NF-kappaB pathway- and carcinogenesis-related genes during long-term subculture. These differentially expressed genes can be considered to be a gene signature of LCL immortalization or EBV-induced carcinogenesis. Clinical trait-associated expression phenotypes should prove useful in the discovery of new candidate genes for particular traits. PMID- 20590664 TI - Inhibition of cell proliferation by CD44: Akt is inactivated and EGR-1 is down regulated. AB - OBJECTIVE: CD44 is a transmembrane glycoprotein and can facilitate signal transduction by serving as a platform for molecular recruitment and assembly. A number of studies have suggested that CD44 can either positively or negatively regulate cell proliferation. The purpose of this study was to investigate how CD44 can inhibit cell proliferation. MATERIALS AND METHODS: We engineered E6.1 Jurkat cells to express CD44. Importantly, these cells lack endogenous CD44 expression. Molecular pathways involved with cell proliferation were studied using RT(2)-PCR array, siRNA, Western blotting and by employing pharmacological inhibitors of ERK1/2, p38 and the PI3K/Akt pathways. RESULTS: We found that CD44 expression significantly inhibited cell proliferation and down-regulated EGR-1 expression and EGR-1 targets cyclin D1 and cyclin D2. Transfection of control E6.1 Jurkat cells with EGR-1 siRNA also inhibited cell proliferation, confirming its role. Disruption of the PI3K/Akt pathway with pharmacological inhibitors reduced both EGR-1 expression and cell proliferation, recapitulating the properties of CD44 expressing cells. Akt was hypophosphorylated in cells expressing CD44 showing its potential role in negatively regulating Akt activation. Strikingly, constitutively active Akt rescued the proliferation defect showing requirement for active Akt, in our system. CONCLUSION: Our results suggest a novel pathway by which CD44 inactivates Akt, down-regulates EGR-1 expression and inhibits cell proliferation. PMID- 20590666 TI - Long-term proliferation and characterization of human spermatogonial stem cells obtained from obstructive and non-obstructive azoospermia under exogenous feeder free culture conditions. AB - OBJECTIVES: The aim of the present study was to improve efficiency of isolation and to optimize proliferative potential of human spermatogonial stem cells (SSCs) obtained from obstructive azoospermic (OA) and non-obstructive azoospermic (NOA) patients, and further, to characterize these cells for potential use in infertility treatment or study of reproductive biology. MATERIALS AND METHODS: We have applied a cell-sorting method, using collagen and magnetic activated cell separation to overcome obstacles, developing a collection system, and simple long term proliferation system, that yields large numbers of high-purity SSCs from obstructive OA and NOA patients. RESULTS: SSCs derived from OA and NOA patients proliferated and maintained their characteristics for more than 12 passages (>6 months) in vitro. Moreover, the population of cells positive for the SSC-specific markers GFRalpha-1 and integrin alpha6, increased to more than 80% at passage 8. CONCLUSION: These finding may support the idea that in vitro propagation of SSCs could be a useful tool for infertility treatment and study of reproductive biology. PMID- 20590665 TI - Differential proteome and phosphoproteome signatures in human T-lymphoblast cells induced by sirolimus. AB - OBJECTIVES: The present study was designed to investigate early proteome and phosphoproteome changes during inhibition of lymphocyte proliferation induced by sirolimus (SRL). MATERIALS AND METHODS: Proliferation assays were conducted using human CCRF-CEM T lymphoblasts under different SRL concentrations. Total protein lysates after SRL treatment were used to identify significantly regulated proteins and phosphorylated proteins by 2-DE and Q-TOF Ultima Global mass spectrometer. RESULTS AND CONCLUSIONS: Incubation with 2.5 micromol/l SRL resulted in a approximately 70% inhibition of cell proliferation. Cells incubated with 2.5 micromol/l for 30 min showed a differential phosphorylation pattern with one higher (TCPQ) and six lower phosphorylation signals (TBA1B, VIME, HNRPD, ENPL, SEPT9, PLSL). On investigating the differential protein expression, five proteins were found to be up-regulated (ECHB, PSB3, MTDC, LDHB and NDKA) and four were down-regulated (EHD1, AATC, LMNB1 and MDHC). Nine of these differentially regulated proteins/phosphoproteins (TCPQ, TBA1B, VIME, HNRPD, ENPL, ECHB, PSB3, LDHB and LMNB1) showed significant interaction potential, through binding protein YWHAZ using MINT software. CONCLUSIONS: We report for the first time the simultaneous early influence of SRL on phosphorylation status and on protein expression in the total proteome of CCRF-CEM T lymphoblasts and predict that 56% of the proteins interact with each other, highlighting significance of these results. PMID- 20590667 TI - Optimization of culture conditions for endothelial progenitor cells from porcine bone marrow in vitro. AB - OBJECTIVES: The aim of this study was to determine an optimal culture method for porcine bone marrow-derived endothelial progenitor cells (EPCs). MATERIALS AND METHODS: Mononuclear cells (MNCs) were isolated by density centrifugation and differentiated into EPCs in in vitro. At first-passage, EPCs were cultured at different cell densities (5 x 10(3), 1 x 10(4), 2 x 10(4) or 5 x 10(4)/cm(2)) and in basic medium (EGM, medium 199, DMEM or 1640) supplemented with FBS (2%, 5%, 10% or 20%) and different combinations of cytokines (VEGF, VEGF + bFGF, VEGF + bFGF + EGF, or VEGF + bFGF + EGF + IGF), the experiment being based on L(64) (4(21)) orthogonal design. RESULTS AND CONCLUSIONS: This demonstrated that the optimal culture method for our EPCs displayed higher expansion and migration rates as compared to other groups, by analysis of variance; that is, cultured at 1 x 10(4)/cm(2) in M199 supplemented with 10% FBS and VEGF + bFGF + IGF + EGF. Furthermore, percentage of positive cells stained by Dil-ac-LDL and FITC-UEA-1 was more than 65%, and as shown by immunohistochemistry, these cells also stained positively for CD133, CD34 and KDR. The present study indicates that the number and function of porcine EPCs significantly increased when using our optimized culture parameters. PMID- 20590668 TI - Angiotensin AT1 receptor activation mediates high glucose-induced epithelial mesenchymal transition in renal proximal tubular cells. AB - 1. Renal tubular epithelial cells can undergo epithelial to mesenchymal transition (EMT) under hyperglycaemic conditions, which is associated with renal interstitial fibrosis. Activation of the renin-angiotensin system (RAS) is involved in diabetic nephropathy. The present study investigated the positive role of angiotensin AT1 receptors in high glucose-induced EMT in cultured tubular epithelial cells. 2. A rat kidney proximal tubular epithelial cell line (NRK-52E) was used in the present study. Levels of EMT makers, namely E-cadherin and vimentin, were estimated using fluorescence immunocytochemistry, mRNA levels of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AT1 receptors were determined by real-time polymerase chain reaction, protein levels of E-cadherin, vimentin, fibronectin, matrix metallopeptidase (MMP)-9 and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 were analysed by western blotting and the concentrations of angiotensin (Ang) II and transforming growth factor (TGF)-beta1 in the culture medium were determined by enzyme immunoassay and ELISA. 3. High glucose (30 mmol/L) induced EMT and increased the synthesis of fibronectin and MMP-9. Furthermore, high glucose increased AGT, ACE and AT(1) receptor mRNA levels, as well as AngII and TGF-beta1 concentrations in the culture medium and ERK1/2 phosphorylation. Pretreatment of cells for 15 min with the AT1 receptor antagonist losartan (10(-5) mol/L) attenuated high glucose induced increases in TGF-beta1 and ERK1/2 phosphorylation and reduced EMT, as well as the consequent synthesis of fibronectin and MMP-9. 4. The results of the present study suggest that the activated local RAS mediates high glucose-induced EMT. By activating AT1 receptors and stimulating TGF-beta1 synthesis, the elevated local RAS participates in high glucose-induced EMT and increased extracellular matrix secretion. PMID- 20590669 TI - This web supplement is primarily devoted to loading protocols. Introduction. PMID- 20590670 TI - Health care reform and translational medicine. PMID- 20590672 TI - Child health research and the Clinical Translational Science Awards: where have we been and where are we going? PMID- 20590673 TI - Advancing science across the disciplines: An interview with Nobel Laureate Phillip A. Sharp, PhD. PMID- 20590674 TI - The North Carolina Translational and Clinical Sciences Institute: Activities of the Biomedical Informatics CORE. PMID- 20590675 TI - The RNA editor gene ADAR1 is induced in myoblasts by inflammatory ligands and buffers stress response. AB - Muscle atrophy remains a significant concern in multiple inflammatory conditions, including injury, sepsis, cachexia, and HIV-associated wasting. Herein, we show that inflammatory stressors, including TNF-alpha, IFN-gamma, or lipopolysaccharide, potently induced the novel expression of the RNA editor ADAR1, an observation not previously described in muscle cells. We also observed that cytokine stimulation suppressed muscle-associated microRNAs, an observation also not previously demonstrated. To map potential effects of ADAR1 induction in the muscle program, we conducted knockdown and overexpression studies in the mouse C2C12 muscle precursor cell (MPC) line and in primary human MPCs. We show that knockdown of stress-induced ADAR1 increased inflammation-mediated declines in the muscle differentiation markers Myogenin and myosin heavy chain, and knockdown reduced levels of active phosphorylated Akt (phospho-Akt), but had no effect on microRNA transcript levels, suggesting a role for ADAR1 in buffering inflammatory stress effects on myogenic transcription and protein synthesis pathways. In addition, overexpression of recombinant ADAR1 suppressed active phosphorylated double-stranded RNA (dsRNA)-dependent protein kinase (phospho PKR), consistent with a role for ADAR1 in limiting inflammation-driven catabolic atrophy pathways. Collectively, these data identify a novel regulatory role for ADAR1 activation under inflammatory stress to both promote muscle protein synthesis pathways and limit atrophy pathways. PMID- 20590676 TI - Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart. AB - Cardiac gene transfer is an attractive tool for developing novel heart disease treatments. Adeno-associated viral (AAV) vectors are widely used to mediate transgene expression in animal models and are being evaluated for human gene therapy. However, it is not clear which serotype displays the best cardiac tropism. Therefore, we curried out this study to directly compare AAV serotypes 1 9 heart transduction efficiency after indirect intracoronary injection. AAV cytomegalovirus immediate early enhancer promoter (CMV)-luciferase serotypes 1-9 were injected in the left ventricular cavity of adult mice, after cross-clamping the ascending aorta and pulmonary artery. An imaging system was used to visualize luciferase expression at 3, 7, 21, 70, and 140 days postinjection. Echocardiography was performed to evaluate cardiac function on day 140. At the end of the study, luciferase enzyme activity and genome copies of the different AAV serotypes were assessed in several tissues and potential AAV immunogenicity was evaluated on heart sections by staining for macrophage and lymphocyte antigens. Among AAV serotypes 1-9, AAV6 showed the best capability of achieving high transduction levels in the myocardium in a tissue-specific manner, whereas the other serotypes had less cardiac transduction and more extracardiac expression, especially in the liver. Importantly, none of the serotypes tested with this marker gene affected cardiac function nor was associated with inflammation. PMID- 20590677 TI - Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy. AB - The genetic basis of most of dilated cardiomyopathy (DCM) cases remains unknown. A recent study indicated that mutations in a highly localized five amino acid hotspot in exon 9 of RBM20, a gene encoding a ribonucleic acid-binding protein, caused aggressive DCM. We undertook this study to confi rm and extend the nature of RBM20 mutations in another DCM cohort. Clinical cardiovascular data, family histories, and blood samples were collected from patients with idiopathic DCM. DNA from 312 DCM probands was sequenced for nucleotide alterations in exons 6 through 9 of RBM20, and additional family members as possible. We found six unique RBM20 rare variants in six unrelated probands (1.9%). Four mutations, two of which were novel (R634W and R636C) and two previously identified (R634Q and R636H), were identified in a five amino acid hotspot in exon 6. Two other novel variants (V535I in exon 6 and R716Q in exon 9) were outside of this hotspot. Age of onset and severity of heart failure were variable, as were arrhythmias and conduction system defects, but many subjects suffered severe heart failure resulting in early death or cardiac transplantation. This article concludes that DCM in patients with RBM20 mutations is associated with advanced disease. PMID- 20590678 TI - Identifying unpredicted drug benefit through query of patient experiential knowledge: a proof of concept web-based system. AB - Information necessary to recognize unexpected drug efficacy is not routinely collected. Once a drug is approved, opportunities for understanding these phenomena are usually lost within clinical care. We propose that patients are willing to provide a wide range of experiential knowledge about the effects of therapies that is seldom solicited. Experience with various drug therapies might be solicited directly from patients in both structured and unstructured formats. Although the signal to noise ratio is expected to be low, these data, if organized in a constructive manner, could provide a useful hypothesis generation resource for areas of further pharmacologic inquiry. A pilot study was conducted for 18 months; 1,065 individuals using the MyHealthAtVanderbilt.com patient portal clicked on a research link to find more information about the study; 375 completed the survey (response rate of 37%). Of those, 218 patients reported that they were currently taking at least one prescription. Statistical methods applied detected known associations between drugs and their intended effects. This validated the type and frequency of effects being reported by patients and provided evidence for the potential for using patient-supplied information to generate hypotheses related to unexpected positive benefits associated with medications. Improved data filtering and mining methods will be needed to expand this concept. PMID- 20590679 TI - Psychometric properties of the mentor role instrument when used in an academic medicine setting. AB - The Ragins and McFarlin Mentor Role Instrument (RMMRI) was originally developed to measure perceptions of mentoring relationships in research and development organizations. The current study was designed to evaluate the RMMRI's reliability and validity when the instrument was administered to clinical and translational science trainees at an academic medical center. The 33-item RMMRI was administered prospectively to a cohort of 141 trainees at the University of Pittsburgh in 2007-2008. Likert-scale items focused on perceptions of five mentoring roles in the career dimension (sponsor, coach, protector, challenger, and promoter) and six mentoring roles in the psychosocial dimension (friend, social associate, parent, role model, counselor, and acceptor). Outcome items included overall perceptions of mentoring satisfaction and effectiveness. Of 141 trainees, 53% were male, 66% were white, 22% were Asian, and 59% were medical doctors. Mean age was 32 years. Analyses showed strong within-factor inter-item correlations (Pearson Coefficients of 0.57-0.93); strong internal consistency (Cronbach alphas of 0.82-0.97); confirmatory factorial validity, as demonstrated by confirmatory factor analysis of the two mentoring dimensions, 11 mentoring roles, and 33 RMMRI items; and concurrent validity, as demonstrated by strong correlations (Pearson Coefficients of 0.56-0.71) between mentoring dimensions, satisfaction, and effectiveness. This article concludes that the RMMRI shows reliability and validity in capturing the multidimensional nature of mentoring when administered to clinical and translational science trainees in the academic setting. PMID- 20590680 TI - Instruction in the responsible conduct of research: an inventory of programs and materials within CTSAs. AB - The National Institutes of Health (NIH) require instruction in the responsible conduct of research (RCR) as a component of any Clinical and Translational Science Award (CTSA). The Educational Materials Group of the NIH CTSA Consortium's Clinical Research Ethics Key Function Committee (CRE-KFC) conducted a survey of the 38 institutions that held CTSA funding as of January 2009 to determine how they satisfy RCR training requirements. An 8-item questionnaire was sent by email to directors of the Clinical Research Ethics, the Educational and Career Development, and the Regulatory Knowledge cores. We received 78 completed surveys from 38 CTSAs (100%). We found that there is no unified approach to RCR training across CTSAs, many programs lack a coherent plan for RCR instruction, and most CTSAs have not developed unique instructional materials tailored to the needs of clinical and translational scientists. We recommend collaboration among CTSAs and across CTSA key function committees to address these weaknesses. We also requested that institutions send electronic copies of original RCR training materials to share among CTSAs via the CTSpedia website. Twenty institutions submitted at least one educational product. The CTSpedia now contains more than 90 RCR resources. PMID- 20590681 TI - Evaluation of a fiber reinforced drillable bone cement for screw augmentation in a sheep model--mechanical testing. AB - We evaluated the mechanical properties of a novel fiber reinforced calcium phosphate at time zero and after 12 weeks in vivo using a sheep long bone osteotomy model. Time zero data were obtained and compared by pullout testing of 4.5 mm bone screws from bone proper and overdrilled defects of 4.5 and 8 mm diameter. Defects were augmented with: polymethylmethacrylate (PMMA), calcium phosphate, and fiber reinforced calcium phosphate using cadaveric sheep tibiae. Twelve-week data were obtained from explanted tibiae of sheep that underwent unilateral tibial osteotomy surgery repaired with a locking compression plate. The most distal hole was overdrilled to 4.5 or 8 mm diameter, filled with fiber reinforced cement, drilled, tapped and a 4.5 mm screw was placed. Screw holding strength at t= 0 was significantly higher for reinforced when compared to nonreinforced cement, but not different from bone or PMMA in 4.5 mm defects. There was no difference in pullout strength for the 8 mm defect data. After 12 weeks fiber reinforced pullout strength increased by 45% and 8.9% for 4.5 and 8 mm defects, respectively, when compared to t= 0 testing. Fiber reinforced calcium phosphate bone cement can be drilled and tapped to support orthopedic hardware for trauma applications. PMID- 20590682 TI - Vaccines as monotherapy and in combination therapy for prostate cancer. AB - Prostate cancer is the second leading cause of cancer death among men in the United States. Standard-of-care chemotherapy for metastatic castration-resistant prostate cancer is associated with significant but modest survival benefit, indicating a need for alternative and/or additional approaches. The use of therapeutic cancer vaccines for the treatment of prostate cancer represents a novel targeted therapeutic approach. Whereas vaccine strategies are being developed for the treatment of various stages of prostate cancer, this article focuses on novel vaccine strategies for castration-resistant prostate cancer that have been translated into late-stage clinical studies. PMID- 20590683 TI - Sizing up pharmacotherapy for obesity. PMID- 20590684 TI - The importance of kidney transplant pathology to evaluate graft condition and select optimal therapy has been widely acknowledged. Introduction. PMID- 20590686 TI - Prolongation of renal allograft survival by anergic cells: advantages and limitations. AB - Even in the era of pharmacological calcineurin inhibitors, a current major challenge in organ transplantation remains the development of immunosuppressive regimens that protect against rejection. One potentially effective procedure is the use of donor-specific anergic T cells generated ex vivo and adoptively transferred back into the recipient after transplantation. In our own work, we first investigated the effect of anergic cells on the prolongation of graft survival in non-human primates. In six animals, half of the recipients survived for over one yr (all animals died or were killed within eight yr). The cause of death was acute renal failure because of cellular rejection (one), uncontrolled bleeding after renal biopsy (two), hydronephrosis probably because of ureteral stenosis (one), and chronic rejection (one). The remaining animal was killed at the end of the study. No infection, malignancy, or signs of graft versus host disease (GVHD) was observed in any of these monkeys. Except for the one animal that died of acute cellular rejection, there was no evidence of tubular infiltration by mononuclear cells, glomerular damage, or parenchymal necrosis. In all animals surviving for more than one yr, a mild grade of interstitial fibrosis, an increase in mesangial matrix, or glomerulopathy was noted. In two of three monkeys, no vascular narrowing of the luminal area caused by fibrointimal thickening of arteries was noted, and arteriosclerotic change was dominant. In this chapter, we summarize the efficacy and limitations of our strategy. PMID- 20590685 TI - Induction of tolerance in clinical kidney transplantation. AB - Induction of donor-specific tolerance has been an ultimate goal in organ transplantation. Although numerous regimens for the induction of allograft tolerance have been developed in rodents, their application to primates has been limited. The approaches that have been successfully applied in primates can be divided into (i) use of total lymphoid irradiation, (ii) costimulatory blockade, (iii) profound depletion of recipient T cells, (iv) infusion of regulatory cells and (v) donor bone marrow (DBM) infusion/transplantation. Among these approaches, successful allograft tolerance has been achieved in clinical kidney transplantation using DBM transplantation. PMID- 20590687 TI - Histopathology of xenografts in pig to non-human primate discordant xenotransplantation. AB - Xenotransplantation could provide a solution to the critical shortage of organs for transplantation in humans. Swine have been proposed as a suitable donor species. Swine organs, however, when transplanted to primates, are rapidly rejected by hyperacute rejection (HAR) and acute humoral xenograft rejection (AHXR). Both HAR and AHXR are triggered by xenoreactive natural antibodies directed against a specific epitope (galactose alpha1-3 galactose: Gal) on porcine vascular endothelium. In attempt to prevent HAR and AHXR, alpha1,3 galactosyltransferase gene knockout (GalT-KO) pigs have been produced. GalT-KO pig organs do not express the Gal epitope (antigen), and it therefore can eliminate the anti-Gal antibody--Gal antigen immunoreaction in xenotransplantation. We reported our initial study of kidney transplantation from GalT-KO miniature swine to baboons with either immunosuppression protocol or with a tolerance inducing protocol. Here, we discussed the pathology of xenografts in GalT-KO pig to non-human primate kidney transplantation. PMID- 20590688 TI - Findings of graft biopsy specimens within 90 days after ABO blood group incompatible living donor kidney transplantation compared with ABO-identical and non-identical transplantation. AB - As immunosuppressive therapy has advanced, we have markedly improved the outcome of ABO blood group incompatible living donor kidney transplantation. Consequently, graft survival at early phase after ABO-incompatible transplantation has been favorable than ABO-compatible transplantation in Japan. But in these days, it has been assumed that transplant glomerulopathy within one yr after ABO-incompatible kidney transplantation might be significantly precipitated. That may be because of chronic, active antibody-mediated rejection (AMR). We performed kidney graft biopsies at the early phase within 90 d after living donor kidney transplantation that involved the episode and protocol biopsies and studied findings of graft biopsy specimens when compared with ABO incompatible and compatible involving non-identical and identical transplantations. In ABO-incompatible transplant cases, the ratio occurring glomerulitis, especially severe injury of g 2-3, was significantly higher than that of identical and non-identical transplant cases (p < 0.01). There was no significant difference in t score, i score, ptc score and v score between three transplant groups. The cases occurring AMR were concordant with the cases recognized with severe glomerulitis. AMR was difficult to be diagnosed by C4d analysis in ABO-incompatible transplant cases. Glomerular injury score, g score, may be considered as more significant and the injury should be cured thoroughly. PMID- 20590689 TI - Clinicopathological analysis of acute vascular rejection cases after renal transplantation. AB - Histopathological change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathological analysis of AVR cases after renal transplantation (RTX). PATIENTS: AVR was diagnosed in 17 patients from 17 renal transplant patients followed in our institute between January 2003 and September 2008. We retrospectively reviewed these 17 patients. RESULTS: Among 17 cases of AVR, 10 cases were mild (v1 in Banff 07 classification), five were moderate (v2), and two were severe (v3). Interstitial inflammation (i1-i3) was present in all 17 biopsies. Moderate to severe tubulitis (t2-t3) was present in seven biopsies, and transplant glomerulitis (g1-g3) was present in 11, peritubular capillaritis (ptc1 ptc3) was in 15 of 17 biopsies. C4d deposition in peritubular capillary (PTC) was observed in 6 of 17 cases. By assaying with plastic beads coated with anti-human leukocyte antigen (HLA) antigen performed in 17 cases, the circulating ant-HLA alloantibody was detected in 10 patients, of which 5/10 were donor-specific antibodies (DSA). Acute antibody-mediated rejection (AAMR) was diagnosed in three cases. Many of v1 cases, steroid pulse therapy (SP) were effective. In v2 and v3 cases, six of seven were steroid-resistant rejection and were need more anti rejection therapy (ART), such as muromonab CD3 (OKT3) injection, gusperimus (DSG) injection, plasmapheresis, intravenous immune globulin, and injection of rituximab. Ten of 17 patients recovered their renal allograft functions by ART, and 16 of 17 patients' grafts are functioning. Deterioration of renal allografts' function after biopsies was seen in seven patients with one of them lost their graft. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good in present immunosuppression and ART. PMID- 20590690 TI - Analysis of preexisting baseline kidney lesions revealed by biopsy in living kidney donors: relationship with clinical parameters at the time of donation. AB - Because the safety of living organ donors is essential, we have been performing donor kidney biopsy before donation in cases where decision-making regarding suitability is marginal. To clarify the degree to which pathological change in the kidney can be predicted on the basis of clinical data obtained non invasively, we analyzed preexisting lesions found by one-h biopsy in 76 living kidney donors, and compared the findings with clinical parameters at the time of donation. Pathological change in living kidney donors was correlated to some extent with predonation clinical parameters including age, serum creatinine, estimated glomerular filtration rate and presence of hypertension, while the lesions influenced by glucose intolerance were not completely correlated with the results of oral glucose tolerance test. A follow-up study will be required to determine whether these mild histological findings at the time of donation influence long-term outcome in the donor. PMID- 20590691 TI - ABO-incompatible renal transplantation in Epstein syndrome. AB - Epstein syndrome (ES) is an autosomal dominant hereditary disease characterized by hereditary nephritis, sensory deafness, and thrombocytopenia. We herein report the case of a 20-yr-old man with ES who underwent ABO blood type-incompatible living-donor kidney transplantation from his mother. He was given platelet transfusion, and his pre-operative number of platelets were 108 x 10(3)/microL. After transplantation, urine output and the decrease in serum creatinine (sCr) were within the acceptable ranges. On the seventh post-operative day (POD), sCr had risen and urine output decreased. Anti-type A antibody rapidly elevated from <2 times (x2) just before transplantation to 64 times (x64), and the patient required hemodialysis again. Resistance index (RI) by ultrasound increased from an average of 0.5 approximately 0.6 on POD 1 to an average of 0.7 approximately 0.8 on POD 7. However, several biopsies (POD 4, 7, and 10) showed no obvious findings of acute rejection except for intense C4d deposition. Because acute antibody-mediated rejection was not completely ruled out, he was treated with methyl-prednisolone pulse therapy, plasma exchange, cyclophosphamide, and immunoglobulin. Regardless, his titer of anti-type A antibody was still high, and he still presented oliguria. We performed an emergent splenectomy. Consequently, the levels of anti-type A antibody decreased, the RI also dropped to an average of 0.6. However, on POD 19 and 25 (platelets were 27 x 10(3)/microL and 36 x 10(3)/microL), he developed a massive intraperitoneal hematoma around the graft and region of the removed spleen, which pushed the graft out and caused acute tubular necrosis, resulting in anuria. The RI rose to an average of 0.8 approximately 1.0 after these episodes. He also experienced bleeding from a duodenal ulcer on POD 21. However, his renal function has fully recovered after acute hemodialysis for 35 d. The latest sCr was 1.5 mg/dL with a recovery in RI to 0.6. Although his platelet count was maintained at a minimum of 50 x 10(3)/microL, he had several severe bleeding episodes, concluding that sufficient platelets are necessary after transplantation in ES. PMID- 20590692 TI - A case of second renal transplantation with acute antibody-mediated rejection complicated with BK virus nephropathy. AB - We reported a 40-year-old female case of second renal transplantation with antibody-mediated rejection (AMR) complicated by BK virus nephropathy. She started hemodialysis (HD) at the age of 17 because of IgA nephropathy. At the age of 18, she underwent living-donor kidney transplantation from her father, but two and a half years after transplantation, she developed chronic rejection. This time, she received cadaveric renal transplantation under the negative cross-match (AHG-LCT), and HLA-AB 1 mismatch and -DR 1 mismatch. Immunosuppressive therapy was initiated using the following four immunosuppressants: methylprednisolone, mycophenolate mofetil, cyclosporine, and basiliximab. However, renal graft showed delayed function, the biopsy showed glomerulitis (g2), endarteritis (v1), and cellular infiltration (ptc3) consisting mainly of mononuclear cells in the peritubular capillary with diffusely positive C4d and anti-SV 40 large T-antigen positive renal tubular epithelial cells on post-operative day 19. The donor specific antibody for HLA-B46 was proven by the LAB screen method. We performed plasma exchange three times and administered immunoglobulin (15 g in total). Then, methylprednisolone pulse therapy was added, and the serum creatinine (SCr) levels gradually decreased. On post-operative day 44, the patient was removed from HD and was discharged with SCr level of 3.3 mg/dL. PMID- 20590693 TI - Plasma cell-rich acute rejection after renal transplantation in a patient with pyoderma gangrenosum: a case report. AB - A 40-yr-old female received a living-related renal transplantation on January 29, 2008. She had type I diabetes mellitus and pyoderma gangrenosum (PG). Induction immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, basiliximab, and prednisolone. Intravenous methylprednisolone pulse therapy was administered to prevent ulceration at the surgical site. The postoperative outcome was almost uneventful, and renal graft function was well preserved for 11 months. Her graft function deteriorated on December 24, 2008 and thus an episode biopsy was performed. The histopathological findings were consistent with plasma cell-rich acute rejection (PCAR). During hospitalization, it was noted that the patient was non-compliant. We then performed steroid pulse therapy, and her graft function and histological findings improved. This is the first report of PCAR in a patient with PG who received a renal allograft. It was thought that PCAR was triggered because of her non-compliance. Thus, we should recognize the importance of enhancing compliance in transplant recipients. PMID- 20590694 TI - A case report of recurrence of mixed cryoglobulinemic glomerulonephritis in a renal transplant recipient. AB - Recurrence of glomerulonephritis (GN) is one of the major risk factors of long surviving renal graft dysfunction. Cryoglobulinemic glomerulonephritis of hepatitis-C virus (HCV)-negative patient is a rare cause of end-stage renal disease. There is little case report of recurrent cryoglobulinemic glomerulonephritis in negative HCV recipients after renal transplantation. We represent a renal allograft recipient of an interesting recurrent cryoglobulinemic glomerulonephritis. The patient was diagnosed with mixed cryoglobulinemic glomerulonephritis by kidney biopsy at the age of 32 . He had no HCV, HBV nor liver dysfunction. He received immunosuppressive therapy, however, was introduced to hemodialysis treatment after 13 yr. He received a cadaveric renal transplantation at the age of 50, and immunosuppressive treatment was started with ciclosporin, prednisolone and mycophenolate mofetil (MMF). Four yr after transplantation, he developed fever and purpura of lower limbs. His serum creatinine level did not increase, however, proteinuria, hematuria, hypocomplementemia, positive rheumatoid factor and mixed cryoglobulinemia were noted. Detailed analysis failed to reveal the composition of mixed cryoglobulinemia. The renal allograft biopsy showed membranoproliferative-type GN with monocyte and polynuclear leukocyte accumulation of capillary loops and small cellular crescent. Immunofluorescent study showed C3, IgG and IgM deposition of mesangial and capillary pattern. Regardless of steroid pulse therapy, hypocomplementemia and positive rheumatoid factor did not improve. Ten yr after transplantation, he was affected by cellulitis and sepsis. Afterward, rising of serum creatinine and nephrotic range proteinuria developed. The allograft biopsy revealed advanced cryoglobulinemic glomerulonephritis with characteristic vascular lesions. Electron microscopy showed organized subendothelial deposits compatible with cryoglobulinemic glomerulonephritis and proteinaceous thrombus in arteriole. PMID- 20590695 TI - Successful treatment of recurrent focal segmental glomerulosclerosis combined with calcineurin inhibitor nephrotoxicity four yr after kidney transplantation. AB - A 31-yr-old Japanese man with end-stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent living related kidney transplantation at the age of 26 yr. The allograft functioned well immediately after surgery, and we did not observe histological findings of rejection and recurrent FSGS in protocol biopsies at two months and one yr after transplantation. Four years after transplantation, the urine protein excretion reached 11 g/d, and the serum creatinine increased over 2.5 mg/dL. We diagnosed nephrotic syndrome due to recurrent FSGS with graft dysfunction and confirmed FSGS lesions with severe endothelial injury with an allograft biopsy, associated with calcineurin inhibitor (CNI) nephrotoxicity. Thereafter, we performed plasmapheresis and steroid therapy with subsequent low-density lipoprotein adsorption, combined with the reduction of tacrolimus. The nephrotic syndrome improved dramatically with the multiple therapeutic approaches. Primary FSGS recurs frequently in patients immediately after kidney transplantation. Post transplant FSGS has various causes, such as recurrent primary disease, obesity, hyperfiltration, donor-related nephrosclerosis, and CNI-induced arteriolopathy. In the case of nephrotic syndrome after kidney transplantation, we should consider not only recurrent FSGS, but also CNI-induced nephrotoxicity to determine the optimal treatment. PMID- 20590696 TI - Two distinct FSGS lesions caused by distinct etiology confirmed in a single patient in pre- and post-transplantation. AB - At the age of three yr, a male patient had surgical treatment for bilateral vesicoureteral reflux (VUR), and at the age of 19 yr, he developed nephrotic syndrome because of focal segmental glomerulosclerosis (FSGS). His renal function deteriorated despite treatment with temocapril and aspirin, and dialysis treatment was started when he was 19. After nine yr of dialysis, he received a living kidney transplantation from his 58-yr-old father, who had a long history of hypertension. A graft biopsy before perfusion showed moderate arteriolosclerosis. As urine protein increased to 2.15 g/d at 16 months after kidney transplantation, the graft biopsy was performed again. FSGS lesion with severe arteriosclerosis was recognized under light microscope, while the effacement of podocyte foot processes was seldom observed. The alteration of calcineurin inhibitor from cyclosporine to tacrolimus, combined with the new administration of angiotensin receptor antagonist (valsartan) and aldosterone receptor blocker, successfully decreased the amount of urine protein to 0.8 g/d within two wk. We considered that the present case showed two distinct types of FSGS lesions--one because of VUR and the other because of cyclosporine arteriolopathy--in each native kidney and transplanted kidney. PMID- 20590697 TI - Protocol biopsies for focal segmental glomerulosclerosis treated with plasma exchange and rituximab in a renal transplant patient. AB - We discuss a renal transplant patient with focal segmental glomerulosclerosis (FSGS) treated with plasma exchange and rituximab. A 45-yr-old woman underwent cadaveric renal transplantation in May 2008. She had started hemodialysis support in 1991. Immediately after transplantation, massive proteinuria (1-5 g/d) appeared. Graft biopsy at one h showed minor glomerular abnormalities with partial foot process effacement on electric microscopy. Protocol biopsy at three months after transplantation for persistent proteinuria showed obvious FSGS under light microscopy. Plasma exchange and rituximab administration were subsequently initiated in August 2008, and proteinuria disappeared within a month after starting these treatments. Protocol graft biopsy one yr after transplantation (2009) showed increased global sclerosis and a decrease in segmental sclerosis. In addition, foot process effacement had recovered by one yr after transplantation. Plasma exchange and subsequent rituximab administration led to clinical remission of post-transplant FSGS with improvement in podocyte structure. Rituximab should be considered soon after several sessions of plasmapheresis in transplant patients with recurrent FSGS. PMID- 20590698 TI - A case of pregnancy-induced thrombotic thrombocytopenic purpura with a kidney allograft recipient. AB - A 32-yr-old female patient, who had been suffering from diffuse crescentic glomerulonephritis and a consequent end-stage renal disease, successfully underwent living-related ABO-incompatible kidney transplantation after a desensitization therapy including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the recipient became pregnant. At the 17th gestational week, the patient was admitted for the management of pregnancy-induced hypertension and aggressive deterioration of kidney graft function. At the 21st gestational week, the patient lost her kidney graft and was re-induced into regular hemodialysis. The patient was also suffering from progressive hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent with acute T-cell-mediated rejection. The patient immediately underwent plasma exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia and intrauterine growth retardation progressed. The patient underwent a caesarian section at the 24th gestational week. Consequently, her platelet count recovered drastically. However, the patient lost her neonate five d after giving a birth, and the patient's graft function had never recovered. PMID- 20590700 TI - Abstracts of the Association of Coloproctology of Great Britain and Ireland Annual Meeting. June 28-30, 2010. Bournemouth, United Kingdom. PMID- 20590699 TI - Progressive interstitial fibrosis of kidney allograft early after transplantation from a non-heart beating donor: possible role of persistent ischemic injury. AB - The donor was 63-yr-old woman with subarachnoid hemorrhage. As she developed severe hypotension for more than four h before cardiac arrest, we biopsied the grafts and decided to transplant those kidneys. Recipient 1 was a 23-yr-old man on 13-yr dialysis program. After 19 d of delayed graft function (DGF), we discontinued hemodialysis (HD). However, the decrease in serum creatinine (sCr) was poor. The minimum sCr was 4.3 mg/dL on post-operative day (POD) 40, and increased to 6.5 mg/dL. The contralateral graft was transplanted to a 61-yr-old man (recipient 2) with 18-yr HD. After 15 d of DGF period, sCr decreased gradually and has been stable at 1.9 mg/dL. In recipient 1, graft biopsies performed on POD 15, 69, and 110, revealed progressive interstitial fibrosis and tubular atrophy (IF/TA) without evidences of acute rejection, tacrolimus associated injury, reflux nephropathy, or viral nephropathy. The second biopsy on POD 69 showed typical findings of acute tubular necrosis. We compared the clinical courses of the two recipients because certain features of recipient 1, such as age, duration of HD, total ischemic time, and body size were advantageous, whereas graft function was poorer than that in recipient 2. Recipient 1 developed severe anemia following the dissociation of graft function from recipient 2. In this case, posttransplant anemia and lower blood pressure might promote IF/TA through persistent ischemic tubular damage, and positive CMV antigenemia and its treatment could promote anemia. Especially in the kidney allograft from a marginal donor, we should consider various factors to obtain a better graft outcome. PMID- 20590701 TI - How appropriate that another special issue of Dermatologic Surgery is devoted to vein treatment. Introduction. PMID- 20590702 TI - Sclerotherapy of varicose veins with polidocanol based on the guidelines of the German Society of Phlebology. AB - BACKGROUND: Sclerotherapy involves the injection of a sclerosing agent for the elimination of intracutaneous, subcutaneous, and transfascial varicose veins. OBJECTIVE: To update guidelines for sclerotherapy of varicose veins. METHODS: The guidelines for sclerotherapy of varicose veins of the German Society of Phlebology were updated and modified through a review of the available literature. RESULTS: Published clinical series and controlled clinical trials provide evidence to support the elimination of intracutaneous and subcutaneous varicose veins using sclerotherapy. Allergic skin reactions occur occasionally as allergic dermatitis, contact urticaria, or erythema. Anaphylaxis is rare. Transient migraine headaches present more frequently in patients treated with foam sclerotherapy than liquid sclerotherapy. CONCLUSION: Sclerotherapy is the method of choice for the treatment of small-caliber varicose veins (reticular varicose veins, spider veins). If performed properly, sclerotherapy is an efficient treatment method with a low incidence of complications. PMID- 20590703 TI - Choosing the appropriate sclerosing concentration for vessel diameter. AB - With the development of novel sclerosing solutions, there has been an increase of choice in which sclerosant to utilize for a particular varicosity. It is not only important for the practitioner to define which sclerosant may be effective in a given clinical scenario, but also identify the minimal sclerosant concentration (MSC) that will produce effective results. This article will overview the salient points of choosing the appropriate sclerosant as well as review which MSC to choose based on patient profile, physician experience, FDA recommendations, and vessel diameter to maximize clinical outcomes while decreasing adverse effects. PMID- 20590704 TI - Commentary: Choosing the appropriate sclerosing concentration for vessel diameter. PMID- 20590705 TI - Review of published information on foam sclerotherapy. AB - BACKGROUND: New data on foam sclerotherapy of varicose veins has been recently published. OBJECTIVE: To identify the current treatment modalities and their effectiveness in use of foam sclerotherapy. MATERIALS AND METHODS: Review of the recent literature regarding clinical treatment of varicose veins using foam sclerotherapy, with emphasis on safety and efficacy. RESULTS Foam sclerotherapy of the great saphenous vein is more effective than liquid. Higher sclerosant concentrations tend to induce higher occlusion. Catheter-assisted sclerotherapy may further improve occlusion rates. To achieve adequate occlusion, vein diameter and volume of foam must be matched. If a critical foam volume is exceeded, the risk of deep venous thrombosis increases. Foam sclerotherapy offers the possibility of using lower sclerosant concentrations than with liquids. Foam sclerotherapy can also be used in venous malformations and periulcerous tributaries. Side effects are hyperpigmentation, skin necrosis, scotoma, and thromboembolic events. Thromboembolism prophylaxis is necessary only in patients with special risk factors. CONCLUSION: Foam sclerotherapy has significantly better efficacy than liquid. It is essential to select the correct concentration and the correct foam volume. In the hands of an experienced physician, foam sclerotherapy is a safe and effective option for treating varicose veins. PMID- 20590706 TI - The French polidocanol study on long-term side effects: a survey covering 3,357 patient years. AB - BACKGROUND: AIMS Short- and mid-term side effects of sclerotherapy, in particular with polidocanol (lauromacrogol 400), have been previously described in our registry of 12,173 sessions. The objective of this follow-up registry was to evaluate the long-term incidence of adverse events with polidocanol. METHODS: The physicians involved in the initial French registry were contacted and asked to partake in the follow-up survey. Initially included patients were controlled at the latest possible date to determine whether a complication had occurred after the end of the initial survey. RESULTS: Data on 1,605 patients included in the French registry were reviewed with a maximum follow-up of 60 months, covering 3,357 patient years. Five (0.4%) adverse events were observed in patients treated with liquid polidocanol and 46 (1.1%) in patients treated with polidocanol foam. The most frequent side effects were visual disturbances (n=14), and the most severe were muscular vein thrombosis (n=8). The onset of side effects was mostly observed directly after sclerotherapy or in the 6 months after (84% in the first year). One deep vein thrombosis recurrence occurred in a patient with heterozygote Factor V Leiden after stopping anticoagulant treatment (foam sclerotherapy). CONCLUSIONS: Foam sclerotherapy is a recognized reference method in the treatment of varicose veins of all types. This study demonstrates that polidocanol is a safe sclerosing agent in the short and long term. PMID- 20590707 TI - Clinical and technical follow-up after sclerotherapy. PMID- 20590708 TI - Sclerosants: a comparative review. AB - BACKGROUND: Sclerotherapy is popular for the treatment of lower extremity telangiectasias and varicose and reticular veins. Although a large number of sclerosants are commonly employed, there are few data that directly compare their advantages and drawbacks. OBJECTIVES: To analyze and present the differences between sclerosants that make them more or less suitable agents in specific clinical applications. MATERIALS AND METHODS: A systemic review of published medical literature that compares and contrasts different classes of sclerosants is presented. RESULTS: There is no perfect sclerosant that is complication free and 100% effective. The ability to match the sclerosant to the clinical problem being approached makes the availability of more Food and Drug Administration approved sclerosants appealing. CONCLUSION: Modern sclerosants that have been subjected to rigorous experimental and clinical trials will provide even more efficacious and safer patient treatments. PMID- 20590709 TI - Foam sclerotherapy for reticular veins and nontruncal varicose veins of the legs: a retrospective review of outcomes and adverse effects. AB - BACKGROUND: Sclerotherapy is the criterion standard of treatment for reticular veins. Foam sclerotherapy is safe and effective, although current guidelines limit the volume of foam used per session. OBJECTIVE: To demonstrate the safety and efficacy of large-volume foam sclerotherapy for the treatment of reticular and nontruncal leg veins. METHODS & MATERIALS: A retrospective review was conducted on all patients undergoing sclerotherapy from 2003 to 2009. Contacted patients graded side effect severity and the degree of vein resolution on a 4 point scale (0-3). The occurrence of cardiovascular or pulmonary events was also recorded. Sclerosant volumes were retrieved from patient records. RESULTS: One thousand one hundred eighty-seven patients underwent sclerotherapy; 419 were successfully contacted of whom 325 had received foam sclerotherapy. The average volume of foam used per session was 16.9 mL. The average rating of adverse events was minimal to mild for all categories including hyperpigmentation (0.35), ulceration (0.06), pain (0.22), and matting or new vessel formation (0.70). The average improvement score was 1.94 (moderate improvement). No serious adverse events occurred. CONCLUSION: Large-volume foam sclerotherapy appears to be safe and effective in the treatment of intracutaneous leg varicosities. Serious adverse events are a rare occurrence, even with sclerosant treatment volumes exceeding current guidelines. PMID- 20590710 TI - Adding sclerotherapy to your practice. PMID- 20590711 TI - My sclerotherapy technique for telangiectasia and reticular veins. AB - BACKGROUND: Sclerotherapy is an effective treatment for reticular and telangiectatic leg veins. OBJECTIVE: To highlight the author's treatment technique. METHOD: Review rational for technique supported by experience and literature. RESULTS: Excellent results have been achieved using the technique presented. CONCLUSIONS: Properly performed sclerotherapy is safe and effective in permanently eliminating unwanted reticular and telangiectatic leg veins. PMID- 20590712 TI - Nonvisible insufficient subcutaneous reticular venous plexus can be observed through the skin using a new illumination method. AB - BACKGROUND: Insufficient subcutaneous reticular venous plexus (ISRVP) is an overlooked disease because the human eye cannot see many of the insufficient veins. OBJECTIVE: To present a total reticular vision (TRV) method that exposes nonvisible ISRVP to normal vision. METHOD & MATERIALS: TRV used visual-spectrum white and red light of 700 nm and infrared light of 15 to 850 nm from an ultradigital viewer camera. We studied 124 asymptomatic subjects from the general population without visible ISRVP. Another six patients with ISRVP without other venous pathology were compared with six healthy controls, Very low pressure was applied to the proximal thigh, and minimal volume increments on the medial malleolus were photoplethysmographically registered to validate subcutaneous venous reflux. RESULTS: Total reticular vision exposed ISRVP on the lower extremities in 72 of 124 subjects (58%), with observed damaged veins corresponding to more than 90% of nonvisible and 5% of visible portions of ISRVP. Subcutaneous reflux was registered only in patients with ISRVP. CONCLUSION: Total reticular vision exposed more than 90% of nonvisible ISRVP, a new pathology, allowing for the study of its relationship with other superficial venous insufficiencies. The authors have indicated no significant interest with commercial supporters. PMID- 20590713 TI - Visualized sclerotherapy of varicose veins. AB - BACKGROUND: The spread and movement of sclerosant after injection during sclerotherapy is difficult to monitor. OBJECTIVE: To develop a new visualization method that allows monitoring of sclerosant dosage and flow during sclerotherapy. METHODS: We used a photodynamic eye (PDE) to perform indocyanine green (ICG) imaging. ICG produces strong fluorescence detectable using PDE and allows monitoring of sclerosant spread through blood vessels in real time. We performed visualized sclerotherapy on 50 limbs, comprising high ligation and sclerotherapy (35 limbs), stripping and sclerotherapy (10 limbs), and sclerotherapy alone (5 limbs). RESULTS: In all cases, fluorescence imaging of the injected sclerosant was possible. No complications resulted from combining ICG and polidocanol in any of the patients, all of whom received follow-up evaluations at 1 week, 1 month, and 3 months after treatment. CONCLUSIONS: Our new method not only avoids the risk of radiation exposure, but also allows for simple observation of sclerosant range of access, determination of the dosage for each lesion, and accurate administration of therapy to target lesions. This method will contribute to further advances in sclerotherapy, given that it allows administration of sclerosant and visual confirmation of optimal injection dosage, speed, and movement of sclerosant after injection. The authors have indicated no significant interest with commercial supporters. PMID- 20590714 TI - Localized hypertrichosis after sclerotherapy. PMID- 20590715 TI - More on hypertrichosis after sclerotherapy. PMID- 20590716 TI - Letter: Polidocanol sclerotherapy for the treatment of pyogenic granuloma. PMID- 20590717 TI - Essentialism in the absence of language? Evidence from rhesus monkeys (Macaca mulatta). AB - We explored whether rhesus monkeys (Macaca mulatta) share one important feature of human essentialist reasoning: the capacity to track category membership across radical featural transformations. Specifically, we examined whether monkeys--like children (Keil, 1989)--expect a transformed object to have the internal properties of its original category. In two experiments, monkeys watched as an experimenter visually transformed a familiar fruit (e.g. apple) into a new kind of fruit (e.g. coconut) either by placing a fruit exterior over the original, or by removing an exterior shell and revealing the inside kind of fruit. The experimenter then pretended to place an inside piece of the transformed fruit into a box which the monkey was allowed to search. Results indicated that monkeys searched the box longer when they found a piece of fruit inconsistent with the inside kind, suggesting that the monkeys expected that the inside of the transformed fruit would taste like the innermost kind they saw. These results suggest that monkeys may share at least one aspect of psychological essentialism: they maintain category-specific expectations about an object's internal properties even when that object's external properties change. These results therefore suggest that some essentialist expectations may emerge in the absence of language, and thus raise the possibility that such tendencies may emerge earlier in human development than has previously been considered. PMID- 20590718 TI - Rapid processing of letters, digits and symbols: what purely visual-attentional deficit in developmental dyslexia? AB - Visual-attentional theories of dyslexia predict deficits for dyslexic children not only for the perception of letter strings but also for non-alphanumeric symbol strings. This prediction was tested in a two-alternative forced-choice paradigm with letters, digits, and symbols. Children with dyslexia showed significant deficits for letter and digit strings but not for symbol strings. This finding is difficult to explain for visual-attentional theories of dyslexia which postulate identical deficits for letters, digits and symbols. Moreover, dyslexics showed normal W-shaped serial position functions for letter and digit strings, which suggests that their deficit is not due to an abnormally small attentional window. Finally, the size of the deficit was identical for letters and digits, which suggests that poor letter perception is not just a consequence of the lack of reading. Together then, our results show that symbols that map onto phonological codes are impaired (i.e. letters and digits), whereas symbols that do not map onto phonological codes are not impaired. This dissociation suggests that impaired symbol-sound mapping rather than impaired visual attentional processing is the key to understanding dyslexia. PMID- 20590720 TI - Categorization, categorical perception, and asymmetry in infants' representation of face race. AB - The present study examined whether 6- and 9-month-old Caucasian infants could categorize faces according to race. In Experiment 1, infants were familiarized with different female faces from a common ethnic background (i.e. either Caucasian or Asian) and then tested with female faces from a novel race category. Nine-month-olds were able to form discrete categories of Caucasian and Asian faces. However, 6-month-olds did not form discrete categories of faces based on race. In Experiment 2, a second group of 6- and 9-month-olds was tested to determine whether they could discriminate between different faces from the same race category. Results showed that both age groups could only discriminate between different faces from the own-race category of Caucasian faces. The findings of the two experiments taken together suggest that 9-month-olds formed a category of Caucasian faces that are further differentiated at the individual level. In contrast, although they could form a category of Asian faces, they could not discriminate between such other-race faces. This asymmetry in category formation at 9 months (i.e. categorization of own-race faces vs. categorical perception of other-race faces) suggests that differential experience with own- and other-race faces plays an important role in infants' acquisition of face processing abilities. PMID- 20590721 TI - Faces are special for newly hatched chicks: evidence for inborn domain-specific mechanisms underlying spontaneous preferences for face-like stimuli. AB - It is currently being debated whether human newborns' preference for faces is due to an unlearned, domain-specific and configural representation of the appearance of a face, or to general mechanisms, such as an up-down bias (favouring top-heavy stimuli, which have more elements in their upper part). Here we show that 2-day old domestic chicks, visually naive for the arrangement of inner facial features, spontaneously prefer face-like, schematic, stimuli. This preference is maintained when the up-down bias is controlled for (Experiment1) or when put in direct conflict with facedness (Experiment 4). In contrast, we found no evidence for the presence of an up-down bias in chicks (Experiment 2). Moreover, our results indicate that the eye region of stimuli is crucial in determining the expression of spontaneous preferences for faces (Experiments 3 and 4). PMID- 20590722 TI - Analogical reasoning ability in autistic and typically developing children. AB - Recent studies (e.g. Dawson et al., 2007) have reported that autistic people perform in the normal range on the Raven Progressive Matrices test, a formal reasoning test that requires integration of relations as well as the ability to infer rules and form high-level abstractions. Here we compared autistic and typically developing children, matched on age, IQ, and verbal and non-verbal working memory, using both the Raven test and pictorial tests of analogical reasoning. Whereas the Raven test requires only formal analogical reasoning, the other analogy tests require use of real-world knowledge, as well as inhibition of salient distractors. We found that autistic children performed as well as controls on all these tests of reasoning with relations. Our findings indicate that the basic ability to reason systematically with relations, for both abstract and thematic materials, is intact in autism. PMID- 20590723 TI - Brain activation during upright and inverted encoding of own- and other-age faces: ERP evidence for an own-age bias. AB - We investigated the neural processing underlying own-age versus other-age faces among 5-year-old children and adults, as well as the effect of orientation on face processing. Upright and inverted faces of 5-year-old children, adults, and elderly adults (> 75 years of age) were presented to participants while ERPs and eye tracking patterns were recorded concurrently. We found evidence for an own age bias in children, as well as for predicted delayed latencies and larger amplitudes for inverted faces, which replicates earlier findings. Finally, we extend recent reports about an expert-sensitive component (P2) to other-race faces to account for similar effects in regard to other-age faces. We conclude that differences in neural activity are strongly related to the amount and quality of experience that participants have with faces of various ages. Effects of orientation are discussed in relation to the holistic hypothesis and recent data that compromise this view. PMID- 20590724 TI - Social categories guide young children's preferences for novel objects. AB - To whom do children look when deciding on their own preferences? To address this question, 3-year-old children were asked to choose between objects or activities that were endorsed by unfamiliar people who differed in gender, race (White, Black), or age (child, adult). In Experiment 1, children demonstrated robust preferences for objects and activities endorsed by children of their own gender, but less consistent preferences for objects and activities endorsed by children of their own race. In Experiment 2, children selected objects and activities favored by people of their own gender and age. In neither study did most children acknowledge the influence of these social categories. These findings suggest that gender and age categories are encoded spontaneously and influence children's preferences and choices. For young children, gender and age may be more powerful guides to preferences than race. PMID- 20590725 TI - Knowing about not remembering: developmental dissociations in lack-of-memory monitoring. AB - Children aged 7 and younger encounter great difficulty in assessing whether lack of memory for an event indicates that the event was not experienced. The present research investigated whether this difficulty results from a general inability to evaluate memory absence or from a specific inability to monitor one feature of memory absence that has been examined in previous studies, namely expected memorability. Seven-, 8- and 9-year-olds, and adults (N = 72) enacted, imagined and confabulated about bizarre and common actions. Two weeks later, participants were asked to recognize the actions that had been enacted. Even 7-year-olds monitored the relative familiarity of rejected distracters (i.e. reported higher confidence for the rejection of novel versus imagined and confabulated distracters). However, only older children and adults exhibited the ability to monitor expected memorability (e.g. reported higher confidence for the rejection of bizarre versus common distracters). These results suggest that young children exhibit specific, rather than general, deficits in monitoring memory absence, and provide an indication of the specific domains in which lack-of-memory monitoring improves during childhood. PMID- 20590726 TI - Selective attention and attention switching: towards a unified developmental approach. AB - We review and relate two literatures on the development of attention in children: one concerning flexible attention switching and the other concerning selective attention. The first is a growing literature on preschool children's performances in an attention-switching task indicating that children become more flexible in their attentional control during the preschool years. The second literature encompasses a large and robust set of phenomena for the same developmental period that indicates a protracted course of development for selective attention in children. We ask whether developmental changes in processes of selective attention may contribute to more flexible attention switching. We consider the two sets of phenomena with respect to this question and propose an empirical agenda for their joint study that may lead ultimately to a unified account of the development of selective attention and attention switching. PMID- 20590727 TI - Narrative skill in children with early unilateral brain injury: a possible limit to functional plasticity. AB - Children with pre- or perinatal brain injury (PL) exhibit marked plasticity for language learning. Previous work has focused mostly on the emergence of earlier developing skills, such as vocabulary and syntax. Here we ask whether this plasticity for earlier-developing aspects of language extends to more complex, later-developing language functions by examining the narrative production of children with PL. Using an elicitation technique that involves asking children to create stories de novo in response to a story stem, we collected narratives from 11 children with PL and 20 typically developing (TD) children. Narratives were analysed for length, diversity of the vocabulary used, use of complex syntax, complexity of the macro-level narrative structure and use of narrative evaluation. Children's language performance on vocabulary and syntax tasks outside the narrative context was also measured. Findings show that children with PL produced shorter stories, used less diverse vocabulary, produced structurally less complex stories at the macro-level, and made fewer inferences regarding the cognitive states of the story characters. These differences in the narrative task emerged even though children with PL did not differ from TD children on vocabulary and syntax tasks outside the narrative context. Thus, findings suggest that there may be limitations to the plasticity for language functions displayed by children with PL, and that these limitations may be most apparent in complex, decontextualized language tasks such as narrative production. PMID- 20590728 TI - Executive function and the development of belief-desire psychology. AB - In two studies children's performance on tasks requiring the ascription of beliefs and desires was investigated in relation to their executive function. Study 1 (n = 80) showed that 3- and 4-year-olds were more proficient at ascribing subjective, mutually incompatible desires and desire-dependent emotions to two persons than they were at ascribing analogous subjective false beliefs. Replicating previous findings, executive function was correlated with false belief ascription. However, executive function was also correlated with performance on tasks requiring subjective desire understanding. Study 2 (n = 54) replicated these results, and showed that the correlations hold even if age, vocabulary and working memory are controlled for. The results are discussed with regard to the role of executive function and conceptual change in theory of mind development. PMID- 20590729 TI - Perceived quality of maternal care in childhood and structure and function of mothers' brain. AB - Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers. PMID- 20590730 TI - The application of bioengineering of acupuncture to the treatment of diabetes, insulin resistance and obesity. PMID- 20590731 TI - Acupuncture: is it effective for treatment of insulin resistance? AB - Insulin resistance (IR) is closely associated with obesity, type 2 diabetes mellitus (T2DM), hypertension, polycystic ovary syndrome (PCOS), non-alcohol fatty liver diseases (NAFLD) and metabolic syndrome and is also a risk factor for serious diseases such as cardiovascular diseases. Pharmacological treatments available for IR are limited by drug adverse effects. Because acupuncture has been practiced for thousands of years in China, it has been increasingly used worldwide for IR-related diseases. This review analyses 234 English publications listed on the PubMed database between 1979 and 2009 on the effectiveness of acupuncture as a treatment for IR. These publications provide clinical evidence, although limited, in support of the effectiveness of acupuncture in IR. At this stage, well-designed, evidence-based clinical randomized controlled trial studies are therefore needed to confirm the effects of acupuncture on IR. Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycemia, overweight, hyperphagia, hyperlipidemia, inflammation, altered activity of the sympathetic nervous system and insulin signal defect, all of which contribute to the development of IR. In addition, acupuncture has the potential to improve insulin sensitivity. The evidence has revealed the mechanisms responsible for the beneficial effects of acupuncture, though further investigations are warranted. PMID- 20590732 TI - Potential manipulation of endothelial progenitor cells in diabetes and its complications. AB - Diabetes mellitus increases cardiovascular risk through its negative impact on vascular endothelium. Although glucotoxicity and lipotoxicity account for endothelial cell damage, endothelial repair is also affected by diabetes. Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. For these reasons, EPCs are thought to have a protective impact within the cardiovascular system. In addition, EPCs appear to modulate the functioning of other organs, providing neurotropic signals and promoting repair of the glomerular endothelium. The exact mechanisms by which EPCs provide cardiovascular protection are unknown and the definition of EPCs is not standardized. Notwithstanding these limitations, the literature consistently indicates that EPCs are altered in type 1 and type 2 diabetes and in virtually all diabetic complications. Moreover, experimental models suggest that EPC-based therapies might help prevent or reverse the features of end-organ complications. This identifies EPCs as having a novel pathogenic role in diabetes and being a potential therapeutic target. Several ways of favourably modulating EPCs have been identified, including lifestyle intervention, commonly used medications and cell-based approaches. Herein, we provide a comprehensive overview of EPC pathophysiology and the potential for EPC modulation in diabetes. PMID- 20590734 TI - Additive actions of the cannabinoid and neuropeptide Y systems on adiposity and lipid oxidation. AB - AIMS: Energy homeostasis is regulated by a complex interaction of molecules and pathways, and new antiobesity treatments are likely to require multiple pharmacological targeting of anorexigenic or orexigenic pathways to achieve effective loss of excess body weight and adiposity. Cannabinoids, acting via the cannabinoid-1 (CB1) receptor, and neuropeptide Y (NPY) are important modulators of feeding behaviour, energy metabolism and body composition. We investigated the interaction of CB1 and NPY in the regulation of energy homeostasis, hypothesizing that dual blockade of CB1 and NPY signalling will induce greater weight and/or fat loss than that induced by single blockade of either system alone. METHODS: We studied the effects of the CB1 antagonist Rimonabant on food intake, body weight, body composition, energy metabolism and bone physiology in wild-type (WT) and NPY knockout (NPY(-/-)) mice. Rimonabant was administered orally at 10 mg/kg body weight twice per day for 3 weeks. Oral Rimonabant was delivered voluntarily to mice via a novel method enabling studies to be carried out in the absence of gavage-induced stress. RESULTS: Mice with dual blockade of CB1 and NPY signalling (Rimonabant-treated NPY(-/-) mice) exhibited greater reductions in body weight and adiposity than mice with single blockade of either system alone (Rimonabant treated WT or vehicle-treated NPY(-/-) mice). These changes occurred without loss of lean tissue mass or bone mass. Furthermore, Rimonabant-treated NPY(-/-) mice showed a lower respiratory exchange ratio than that seen in Rimonabant-treated WT or vehicle-treated NPY(-/-) mice, suggesting that this additive effect of dual blockade of CB1 and NPY involves promotion of lipid oxidation. On the other hand, energy expenditure and physical activity were comparable amongst all treatment groups. Interestingly, Rimonabant similarly and transiently reduced spontaneous and fasting-induced food intake in WT and NPY(-/-) mice in the first hour after administration only, suggesting independent regulation of feeding by CB1 and NPY signalling. In contrast, Rimonabant increased serum corticosterone levels in WT mice, but this effect was not seen in NPY(-/-) mice, indicating that NPY signalling may be required for effects of CB1 on the hypothalamo-pituitary adrenal axis. CONCLUSIONS: Dual blockade of CB1 and NPY signalling leads to additive reductions in body weight and adiposity without concomitant loss of lean body mass or bone mass. An additive increase in lipid oxidation in dual CB1 and NPY blockade may contribute to the effect on adiposity. These findings open new avenues for more effective treatment of obesity via dual pharmacological manipulations of the CB1 and NPY systems. PMID- 20590733 TI - Decrease in hepatic very-low-density lipoprotein-triglyceride secretion after weight loss is inversely associated with changes in circulating leptin. AB - AIM: Although weight loss usually decreases very-low-density lipoprotein triglyceride (VLDL-TG) secretion rate, the change in VLDL-TG kinetics is not directly related to the change in body weight. Circulating leptin also declines with weight loss and can affect hepatic lipid metabolism. The aim of this study was to determine whether circulating leptin is associated with weight loss induced changes in VLDL-TG secretion. METHODS: Ten extremely obese subjects were studied. VLDL-TG secretion rate and the contribution of systemic (derived from lipolysis of subcutaneous adipose tissue TG) and non-systemic fatty acids (derived primarily from lipolysis of intrahepatic and intraperitoneal TG, and de novo lipogenesis) to VLDL-TG production were determined by using stable isotopically labelled tracer methods before and 1 year after gastric bypass surgery. RESULTS: Subjects lost 33 +/- 12% of body weight, and VLDL-TG secretion rate decreased by 46 +/- 23% (p = 0.001), primarily because of a decrease in the secretion of VLDL-TG from non-systemic fatty acids (p = 0.002). Changes in VLDL TG secretion rates were not significantly related to reductions in body weight, body mass index, plasma palmitate flux, free fatty acid or insulin concentrations. The change in VLDL-TG secretion was inversely correlated with the change in plasma leptin concentration (r = -0.72, p = 0.013), because of a negative association between changes in leptin and VLDL-TG secretion from non systemic fatty acids (r = -0.95, p < 0.001). CONCLUSIONS: Weight loss-induced changes in plasma leptin concentration are inversely associated with changes in VLDL-TG secretion rate. Additional studies are needed to determine whether the correlation between circulating leptin and VLDL-TG secretion represents a cause and-effect relationship. PMID- 20590737 TI - A population model evaluating the costs and benefits associated with different oral treatment strategies in people with type 2 diabetes. AB - AIM: The attainment of near-normal glycaemia is an important feature in reducing complications in people with type 2 diabetes. Current treatment pathways advocate a failure-driven therapy algorithm for blood-glucose lowering that leads to the sequential addition of therapies. The addition and combination of multiple blood glucose lowering agents may be associated with significant side effects, such as weight gain and hypoglycaemia, resulting in a detrimental quality of life. The objective of this study is to quantify the overall costs and quality-adjusted life years (QALY) associated with therapy escalation via oral only treatment strategies with different adverse event profiles as a function of target HbA1c achievement. METHODS: A previously published model was adapted to run as a non terminating simulation model. The model is designed to evaluate the cost utility of treatment strategies in a population of type 2 diabetes mellitus patients. Model outputs include incidence of micro- and macrovascular complications, hypoglycaemia and diabetes-specific and all-cause mortality. RESULTS: The total number of vascular events predicted by the model varied little across the four treatment strategies because of the glycaemic profile associated with each therapy strategy being similar. The strategy with sequential addition of thiazolidinediones (TZDs) and sulphonylureas (SUs) to metformin (MF) was associated with greatest predicted hypoglycaemia burden. The addition of SU and dipeptidyl peptidase (DPP-4) inhibitors to MF was associated with the highest estimated QALYs. CONCLUSIONS: A treatment strategy involving the sequential addition of SU and TZD to first-line MF therapy is associated with the lowest cost and lowest gain across a population, whereas addition of TZD and SU sequentially to first-line MF therapy resulted in the highest cost and incrementally less QALY gain when compared with treatment strategies involving the addition of a DPP-4 inhibitor and SU to first-line MF (irrespective of the treatment sequence) that were associated with both less cost and greatest QALY gain. PMID- 20590736 TI - Efficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind trial. AB - OBJECTIVE: To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase-4 inhibitor) and voglibose (an alpha-glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c > or =6.5% and <10.0%) on diet and exercise. METHODS: In a multi-center, randomized, double-blind, parallel-group study, 319 patients were randomized (1:1) to 12-week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non-inferior to voglibose in lowering HbA1c. RESULTS: After 12 weeks, sitagliptin was non-inferior to voglibose for HbA1c-lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = -0.7% (-0.8 to -0.6) and -0.3% (-0.4 to -0.2), respectively; between-group difference = -0.4% (-0.5 to -0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2-h postmeal glucose (-2.8 mmol/l vs. -1.8 mmol/l, p < 0.001) and fasting plasma glucose (-1.1 mmol/l vs. -0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug-related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups. CONCLUSIONS: In Japanese patients with type 2 diabetes, once-daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice-daily voglibose over 12 weeks. PMID- 20590738 TI - Impact of concurrent macrovascular co-morbidities on healthcare utilization in patients with type 2 diabetes in Europe: a matched study. AB - AIM: To examine and to quantify the impact of concurrent macrovascular co morbidities (MVC) on healthcare resource utilization among patients with type 2 diabetes mellitus (T2DM) in Europe. METHODS: This is a matched cohort study based on the Real-Life Effectiveness and Care Patterns of Diabetes Management study, a multicentre, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, UK, Norway, Finland, Germany and Poland. Included patients were aged > or =30 years at time of diagnosis of T2DM who added a sulfonylurea or a PPARgamma agonist to failing metformin monotherapy (index date) and had concurrent MVC (cases). A control cohort with T2DM but without concurrent MVC was identified using 1:1 propensity score matching. Logit models were used to identify the relationship between concurrent MVC and the likelihood of emergency room admission, receiving medical/surgical procedures, and hospitalization during the study period after controlling for baseline demographics, clinical information and baseline treatment. Negative binomial models were used to predict the number of office visits and length of hospital stay per year attributable to the concurrent MVC. RESULTS: Relative to controls, patients with MVC were significantly more likely to have emergency department admissions [odds ratio (OR) 2.69; 95% CI: 1.56-4.65], receiving medical/surgical procedures (OR 2.57; 95% CI: 1.56-4.21) and hospitalizations (OR 2.58; 95% CI: 1.64-4.07) after controlling for other predictors. Similarly, MVC were associated with 1.49 additional office visits per year (p = 0.036) and 0.32 days of hospital stay per year (p = 0.023). CONCLUSIONS: Within a seven-country European sample, this study showed that T2DM patients with MVC were more likely to use healthcare resources compared with T2DM patients without MVC. PMID- 20590735 TI - Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. AB - AIM: As weight gain and hypoglycaemia associated with glimepiride therapy can negatively impact weight perceptions, psychological well-being and overall quality of life in type 2 diabetes, we investigated whether liraglutide treatment could improve these factors. METHODS: Seven hundred and thirty-two patients with type 2 diabetes completed a 77-item questionnaire during a randomized, 52-week, double-blind study with liraglutide 1.2 mg (n = 245) or 1.8 mg (n = 242) compared with glimepiride 8 mg (n = 245). RESULTS: Mean (SE) decreases in glycated haemoglobin levels were greater with liraglutide 1.2 mg [-0.84 (0.08)%] and 1.8 mg [-1.14 (0.08)%] than glimepiride [-0.51 (0.08)%; p = 0.0014 and p < 0.0001, respectively]. Patients gained weight on glimepiride [mean (SE), 1.12 (0.27) kg] but lost weight on liraglutide [1.2 mg: -2.05 (0.28) kg; 1.8 mg: -2.45 (0.28) kg; both p < 0.0001]. Patient weight assessment was more favourable with liraglutide 1.8 mg [mean (SE) score: 40.0 (2.0)] than glimepiride [48.7 (2.0); p = 0.002], and liraglutide 1.8 mg patients were 52% less likely to feel overweight [odds ratio (OR) 0.48; 95% confidence interval (CI): 0.331-0.696]. Mean (SE) weight concerns were less with liraglutide [1.2 mg: 30.0 (1.2); 1.8 mg: 32.8 (1.2)] than glimepiride [38.8 (1.2); p < 0.0001 and p < 0.001, respectively], with liraglutide groups 45% less likely to report weight concern (OR 0.55, 95% CI: 0.41-0.73). Mean (SE) mental and emotional health and general perceived health improved more with liraglutide 1.8 mg [476.1 (2.8) and 444.2 (3.2), respectively] than glimepiride [466.3 (2.8) and 434.5 (3.2), respectively; p = 0.012 and p = 0.033, respectively]. CONCLUSIONS: Improved glycaemic control and decreased weight with liraglutide 1.8 mg vs. glimepiride can improve psychological and emotional well-being and health perceptions by reducing anxiety and worry associated with weight gain. PMID- 20590740 TI - The effect of intensive glycaemic control on cardiovascular outcomes. AB - The relationship between glycaemia and cardiovascular disease remains controversial. For patients with type 1 diabetes in the Diabetes Control and Complications Trial, intensive glycaemic control reduced microvascular outcomes and, on longer term follow-up, a significant reduction in macrovascular events was observed. For patients with recently diagnosed type 2 diabetes, the findings in the United Kingdom Prospective Diabetes Study were similar; intensive glycaemic control reduced microvascular events during the intervention phase of the study, and a reduction in macrovascular events was observed on longer follow up. More recently, the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation study showed a microvascular benefit of more intensive blood glucose control in patients with longstanding diabetes, whereas the Action to Control Cardiovascular Risk in Diabetes study showed harm if this was performed rapidly, with increase in weight, hypoglycaemia and mortality. Collectively, these studies suggest that slow and steady intensive control of glycaemia improves outcomes in people with diabetes, and that to reduce mortality this should be commenced early in the management of patients with type 2 diabetes. PMID- 20590742 TI - A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects. AB - AIM: The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin. METHODS: The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions. All subjects received, sequentially, matching placebo, 10, 15, 20 and 30 mg IN-105 tablets in five consecutive periods. Tablets were administered 20 min prior to meal in all the periods. Plasma levels of immunoreactive insulin, C-peptide and glucose were measured up to 180 min from the time of dosing. The changes in postprandial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo. RESULTS: Changes in glucose from baseline (mean +/- s.d.) at 140 min (2 h postprandial) were 94.84 +/- 22.3, 79.45 +/- 43.00, 70.68 +/- 35.71, 63.47 +/- 42.75 and 53.06 +/- 47.27 mg/dL, respectively, and exhibited linear dose response. The insulin C(max) values were found to be 50.8 +/- 26.0 mU/L for placebo, 100.3 +/- 66.7 with 10 mg IN-105, 177.69 +/- 150.3 with 15 mg IN-105, 246.2 +/- 245.2 with 20 mg IN-105 and 352.5 +/- 279.3 mU/L with 30 mg of IN-105. CONCLUSIONS: IN-105 absorption is proportional to the dose administered. The 2-h postprandial glucose excursion was reduced in a dose proportional manner. Circulating C-peptide levels were found to be suppressed in proportion to the IN 105 exposure. IN-105 reduces glucose excursion despite lower endogenous insulin secretion. IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied. PMID- 20590741 TI - Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. AB - Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP 4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug-drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. PMID- 20590743 TI - Insulin detemir is a fully efficacious, low affinity agonist at the insulin receptor. AB - AIM: To compare the properties of insulin detemir with human insulin or insulin aspart in various in vitro and in vivo experiments, thereby highlighting the importance of performing dose-response studies when investigating insulin analogues, in this study specifically insulin detemir. METHODS: Displacement of membrane-associated insulin receptors from human and rat hepatocytes, and from Chinese Hamster Ovary cells over-expressing human insulin receptor (CHO-hIR) at varying albumin concentrations is measured. Lipogenesis in primary rat adipocytes over time and the effects in the simultaneous presence of insulin detemir and human insulin or insulin aspart are assessed. The hyperinsulinaemic euglycaemic clamp technique in rats is used to establish dose-response curves for multiple metabolic endpoints and to investigate the effects of the simultaneous presence of insulin detemir and human insulin. RESULTS: Both in vitro and in vivo, insulin detemir shows full efficacy and right-shifted parallel dose-response curves compared with human insulin. The potency estimates are different between the in vivo and in vitro conditions and among different in vitro conditions, that is the potency decreases in vitro with increasing albumin concentration. The effects of insulin detemir and human insulin are additive both in vitro and in vivo. CONCLUSIONS: Insulin detemir is fully efficacious compared with human insulin on all metabolic endpoints measured in vitro and in vivo. The fact that the potency estimates are method-dependent emphasizes the importance of establishing full dose-response relationships when characterizing insulin detemir. PMID- 20590744 TI - Taspoglutide, a novel human once-weekly analogue of glucagon-like peptide-1, improves glucose homeostasis and body weight in the Zucker diabetic fatty rat. AB - AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel class of pharmacotherapy for type 2 diabetes. We investigated the effects of a novel, long acting human GLP-1 analogue, taspoglutide, in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. METHODS: Blood glucose and plasma levels of insulin, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP) and triglycerides were measured during oral glucose tolerance tests (oGTT) conducted in ZDF rats treated acutely or chronically with a single long-acting dose of taspoglutide. Pioglitazone was used as a positive control in the chronic study. Postprandial glucose, body weight, glycaemic control and insulin sensitivity were assessed over 21 days in chronically treated animals. RESULTS: Acute treatment with taspoglutide reduced glucose excursion and increased insulin response during oGTT. In chronically treated rats, glucose excursion and levels of GIP, PYY and triglycerides during oGTT on day 21 were significantly reduced. Postprandial glucose levels were significantly lower than vehicle controls by day 15. A significant reduction in body weight gain was noticed by day 8, and continued until the end of the study when body weight was approximately 7% lower in rats treated with taspoglutide compared to vehicle. Glycaemic control (increased levels of 1,5-anhydroglucitol) and insulin sensitivity (Matsuda index) were improved by taspoglutide treatment. CONCLUSIONS: Taspoglutide showed typical effects of native GLP-1, with improvement in glucose tolerance, postprandial glucose, body weight, glycaemic control and insulin sensitivity. PMID- 20590745 TI - Effect of insulin glargine on glycaemic control and weight in obese and non-obese people with type 2 diabetes: data from the AT.LANTUS trial. AB - AIMS: To explore glucose lowering response to insulin initiation or switch to insulin glargine in obese and non-obese individuals with type 2 diabetes mellitus (T2DM) and to examine weight gain and hypoglycaemic episodes in this group. METHODS: Post hoc subgroup analysis using data of obese and non-obese participants from a large multi-centre (4555 participants with T2DM), multi national 24-week randomized controlled trial of investigator titrated insulin glargine versus patient self-managed titrated insulin glargine. This analysis was carried out to compare two subgroups: obese (> or =30 kg/m2) and non-obese (<30 kg/m2) participants. RESULTS: The mean body mass index (BMI) values were 33.7 kg/m2(n = 1833) and 25.9 kg/m(2)(n = 2755) in obese and non-obese subjects, respectively. There was a significant reduction in glycated haemoglobin (HbA1c) from baseline in both subgroups but no significant difference between subgroups (1.15 vs. 1.15%, p = 0.50). Overall, there was a 1.21 kg (s.d. 3.3) increase in weight in individuals who were non-obese and a 1.08 kg (s.d. 3.9) increase in obese individuals (p = 0.67). There was no significant difference in the proportion of participants achieving an HbA1c of <7.0% at 6 months in both the subgroups (28.8 vs. 27.1%, p = 0.20). In multiple logistic regression, BMI was not a prognostic factor in achieving a target of HbA1c < or = 7.0%. There was no significant difference in severe hypoglycaemic episodes between obese and non obese subgroups (1.3 vs. 1.0%); however, significantly more non-obese individuals experienced nocturnal hypoglycaemic episodes(4.5 vs. 2.4%, p < 0.05). CONCLUSIONS: In this study, treatment with insulin glargine in people with T2DM was associated with a significant reduction in HbA1c without differential increase in weight gain in obese and non-obese subgroups. Rates of severe hypoglycaemia were not different between obese and non-obese subgroups. PMID- 20590746 TI - Effects of interleukin-6 treatment on neurovascular function, nerve perfusion and vascular endothelium in diabetic rats. AB - AIM: Interleukin-6 (IL-6), a member of the neuropoietic cytokine family, participates in neural development and has neurotrophic activity. Recent research has also indicated actions to improve vasa nervorum function in diabetes. Both these facets are potentially relevant for treatment of diabetic neuropathy. The aim of this study was to determine whether IL-6 treatment corrected changes in neurovascular function in streptozotocin-induced diabetic rats. METHODS: After 1 month of diabetes, rats were given IL-6 for 1 month. The rats were subjected to sensory testing and measurements of nerve conduction velocities and nerve blood flow by hydrogen clearance microelectrode polarography. Further groups were used to study responses of the isolated gastric fundus and renal artery. Results were statistically analysed using ANOVA and post hoc tests. RESULTS: Diabetic rats showed mechanical hyperalgesia, thermal hyperalgesia, and tactile allodynia. The former was unaffected by IL-6 treatment, whereas the latter two measures were corrected. Immunohistochemical staining of dorsal root ganglia for IL-6 did not reveal any changes with diabetes or treatment. The results showed that 22 and 17.4% slowing of sciatic motor and saphenous sensory nerve conduction velocities, respectively, with diabetes were improved by IL-6. Sciatic endoneurial perfusion was halved by diabetes and corrected by IL-6. A 40.6% diabetic deficit in maximal non-adrenergic, non-cholinergic relaxation of gastric fundus to nerve stimulation was unaffected by IL-6. Renal artery endothelium-dependent relaxation was halved by diabetes, the endothelium-derived hyperpolarizing factor (EDHF) component being severely attenuated. IL-6 did not affect nitric oxide-mediated vasorelaxation, but markedly improved EDHF responses. CONCLUSIONS: IL-6 improved aspects of small and large nerve fibre and vascular endothelium dysfunction in diabetic rats. The functional benefits related to increased nerve blood flow via an EDHF mechanism, and IL-6 could have therapeutic potential in diabetic neuropathy and vasculopathy, which should be further evaluated. PMID- 20590747 TI - Efficacy and safety of vildagliptin and voglibose in Japanese patients with type 2 diabetes: a 12-week, randomized, double-blind, active-controlled study. AB - AIM: To confirm the efficacy of vildagliptin in patients with type 2 diabetes (T2D) by testing the hypothesis that glycosylated haemoglobin (HbA1c) reduction with vildagliptin is superior to that with voglibose after 12 weeks of treatment. METHODS: In this 12-week, randomized, double-blind, active-controlled, parallel group study, the efficacy and safety of vildagliptin (50 mg bid, n = 188) was compared with that of voglibose (0.2 mg tid, n = 192) in patients with T2D who were inadequately controlled with diet and exercise. RESULTS: The characteristics of two groups were well matched at baseline. The mean age, body mass index (BMI) and HbA1c were 59.1 years, 24.9 kg/m(2) and 7.6%, respectively. At baseline, fasting plasma glucose (FPG) and 2-h postprandial glucose (PPG) were 9.01 mmol/l (162.2 mg/dl) and 13.57 mmol/l (244.3 mg/dl), respectively. The adjusted mean change in HbA1c from baseline to endpoint was -0.95 +/- 0.04% in the vildagliptin treated patients and -0.38 +/- 0.04% in those receiving voglibose (between-group change = 0.57 +/- 0.06%, 95% confidence interval (CI) (-0.68 to -0.46%), p < 0.001), showing that vildagliptin was superior to voglibose. Endpoint HbA1c < or = 6.5% was achieved in 51% vildagliptin-treated patients compared with 24% patients who were on voglibose (p < 0.001). Vildagliptin also exhibited significantly (p < 0.001) greater reduction compared with voglibose in both FPG [1.34 vs. 0.43 mmol/l (24.1 vs. 7.8 mg/dl)] and 2-h PPG [2.86 vs. 1.1 mmol/l (51.5 vs. 19.8 mg/dl)]. Overall adverse events (AEs) were lower in the vildagliptin-treated patients compared with that in the voglibose-treated patients (61.2 vs. 71.4%), with no incidence of hypoglycaemia and serious adverse events with vildagliptin. Gastrointestinal AEs were significantly lower with vildagliptin compared with that of the voglibose (18.6 vs. 32.8%; p = 0.002). CONCLUSIONS: Vildagliptin (50 mg bid) showed superior efficacy and better tolerability compared with voglibose in Japanese patients with T2D. PMID- 20590748 TI - Effect of pioglitazone on endothelial function in impaired glucose tolerance. AB - AIM: Flow-mediated dilation (FMD) is a surrogate marker of endothelial function, which has been proposed as a barometer of vascular health. Impaired microvascular response to reactive hyperaemia is thought to be the mechanism behind reduced shear stress and subsequently impaired FMD, which has been associated with cardiovascular events. This study aims to assess the effect of pioglitazone on the vasculature of patients with impaired glucose tolerance (IGT). MATERIALS AND METHODS: Forty IGT patients with no cardiovascular disease were compared with 24 healthy age- and sex-matched controls. Endothelial function was assessed using FMD of the brachial artery. Adiponectin (ADN) levels were measured and insulin sensitivity was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). A randomised double-blind placebo-controlled trial of the IGT subjects was then performed, with subjects receiving either pioglitazone 30 mg od or matched placebo for 12 weeks before the measurements were repeated. RESULTS: The IGT subjects had a significantly impaired FMD compared with the controls (p < 0.001). Diastolic shear stress (DSS) was also significantly reduced in IGT (p = 0.04). High molecular weight (HMW) ADN was significantly lower in the IGT group than in controls (p = 0.03). On analysis of the IGT group after 12 weeks treatment, FMD was significantly increased in the pioglitazone group compared with placebo (p = 0.03) as was endothelium-independent dilation (EID) (p = 0.03). A significant increase in total ADN (p < 0.001), HMW ADN (p < 0.001) and HMW/total ratio (p = 0.001) occurred in the pioglitazone group compared with placebo. CONCLUSIONS: Pioglitazone improved endothelial function in IGT. Treatment with pioglitazone may reduce the risk of cardiovascular disease in this patient group. PMID- 20590749 TI - Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. AB - AIM: The objectives of the study were to determine whether thiazolidinedione (TZD) use is associated with an increased risk of fracture in men and women with type 2 diabetes mellitus and to compare the effects of pioglitazone and rosiglitazone. MATERIALS AND METHODS: A research database of integrated pharmacy and medical claims was analysed using Cox models adjusted for age, gender, chronic obstructive pulmonary disease, asthma, osteoporosis, stroke, prior fracture and chronic disease score. Patients were followed for 540 days. RESULTS: There was a 39% higher [adjusted hazard ratio (HR), 1.39; 95% confidence interval (CI), 1.32-1.46] incidence of fractures in men and women exposed to a TZD (n = 69047; age = 56 +/- 5 years; 59% men; 48% rosiglitazone) compared with that in control patients (n = 75352; age = 56 +/- 5 years; 51% men). Men treated with a TZD had a higher likelihood of fracture than control patients (adjusted HR rosiglitazone, 1.47; 95% CI, 1.38-1.56; adjusted HR pioglitazone, 1.43; 95% CI, 1.34-1.52). The HRs associated with pioglitazone (adjusted HR, 1.43; 95% CI, 1.34 1.52) and rosiglitazone (adjusted HR, 1.47; 95% CI, 1.38-1.56) were almost identical. TZD use was associated with a higher fracture risk in women aged above and below 50 years and in men aged above 50 years. CONCLUSIONS: Our findings add support to the growing literature that TZD treatment is associated with an increased risk of fractures in both men and women, that effects of rosiglitazone and pioglitazone are similar and that fracture risk is increased even in younger women. PMID- 20590750 TI - Effects of in vitro antagonism of endocannabinoid-1 receptors on the glucose transport system in normal and insulin-resistant rat skeletal muscle. AB - OBJECTIVE: We determined the direct effects of modulating the endocannabinoid-1 (CB1) receptor on the glucose transport system in isolated skeletal muscle from insulin-sensitive lean Zucker and insulin-resistant obese Zucker rats. METHODS: Soleus strips were incubated in the absence or presence of insulin, without or with various concentrations of the CB1 receptor antagonist SR141716 or with the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA). RESULTS: CB1 receptor protein expression in visceral adipose (57%), soleus (40%) and myocardial (36%) tissue was significantly (p < 0.05) decreased in obese compared to lean animals, with a trend for a reduction (17%, p = 0.079) in the liver. In isolated soleus muscle from both lean and obese Zucker rats, CB1 receptor antagonism directly improved glucose transport activity in a dose-dependent manner. Basal glucose transport activity was maximally enhanced between 100 and 200 nM SR141716 in lean (26-28%) and obese (22-31%) soleus. The maximal increase in insulin-stimulated glucose transport for lean muscle ( approximately 30%) was achieved at 50 nM SR141716 and for obese muscle ( approximately 30%) at 100 nM SR141716. In contrast, CB1 receptor antagonism did not alter hypoxia-stimulated glucose transport activity. CB1 receptor agonism (1 mM ACEA) significantly decreased both basal (15%) and insulin-stimulated (22%) glucose transport activity in isolated lean soleus. This effect was reversed by 200 nM SR141716. In both lean and obese muscle, the functionality of key signalling proteins (insulin receptor beta subunit, Akt, glycogen synthase kinase-3beta (GSK-3beta), AMP-dependent protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK)) was not altered by either CB1 receptor agonism or antagonism. CONCLUSION: These results indicate that the engagement of CB1 receptor can negatively modulate both basal and insulin-dependent glucose transport activity in lean and obese skeletal muscles, and that these effects are not mediated by the engagement of elements of the canonical pathways regulating this process in mammalian skeletal muscle. PMID- 20590751 TI - Reactive hypoglycaemia following GLP-1 infusion in pancreas transplant recipients. AB - The aim of the study was to determine whether reactive hypoglycaemia in pancreas transplant recipients that followed administration of glucagon-like peptide-1 (GLP-1) was associated with excessive insulin, insufficient glucagon, or both. Methodology involved six portally drained pancreas recipients who received GLP-1 (1.5 pmol/kg/min) or placebo infusion on randomized occasions during glucose potentiated arginine testing. The second subject developed symptomatic hypoglycaemia [plasma glucose (PG) 42 mg/dl] 1 h after GLP-1 administration; subsequent subjects received intravenous glucose following GLP-1, but not placebo, infusion for PG levels <65 mg/dl. Following GLP-1 vs. placebo infusion, PG was lower (58 +/- 4 vs. 76 +/- 5 mg/dl; p < 0.05) despite administration of intravenous glucose. During hypoglycaemia, insulin levels and the insulin-to glucagon ratio were greater after GLP-1 vs. placebo infusion (p < 0.05), while glucagon did not vary. It can be concluded from the study that GLP-1 can induce reactive hypoglycaemia in pancreas transplant recipients through excessive insulin secretion associated with an increased insulin-to-glucagon ratio. PMID- 20590752 TI - Saxagliptin efficacy. PMID- 20590754 TI - Consensus session for appropriate managements of bleeding non malignant gastro duodenal ulcers, Indication for endoscopic resection of colorectal polyps and surveillance guidelines, and Stone management of the bile duct. Preface. PMID- 20590755 TI - Successful endoscopic extraction of a large impacted choledocholithiasis in the ampulla of vater: two interesting cases. AB - In patients with choledocholithiasis, a stone can sometimes become impacted in the ampulla of Vater, potentially resulting in the complications of acute cholangitis and acute pancreatitis. Endoscopic sphincterotomy and needle knife papillotomy are very effective for the removal of an impacted stone in the ampulla of Vater. Dramatic improvement of the symptoms may be expected if these procedures are performed sufficiently early after the occurrence of the impaction. However, depending on the size, site and situation of the impacted stone, we have often encountered difficulties during endoscopic treatment. We encountered two interesting cases of choledocholithiasis with impaction of large stones in the ampulla of Vater. In Case 1, treatment with radial incisions was added to the usual treatment of needle knife papillotomy, because of the large size of the stone, and the combined treatment was effective. In Case 2, a large periampullary choledochoduodenal fistula was created at the ampulla of Vater, and an indwelling double pigtail tube was placed in the ampulla; the stone then discharged via the tube without additional need for endoscopic sphincterotomy or needle knife papillotomy. Our experience in these cases indicates that innovations in treatment according to the situation of the impacted stone may be needed for the treatment of giant impacted stones in the ampulla of Vater. PMID- 20590756 TI - Needle knife sphincterotomy for an impacted ampullary stone with difficult selective biliary cannulation. AB - Endoscopic treatment is highly effective for extracting common bile duct (CBD) stones and is the most common therapeutic method for CBD stones. For patients with CBD stones, the treatment goal is to completely clear the biliary duct. In general, the successful extraction rate using a basket and/or balloon catheter is as high as 90%. However, stones that are resistant to conventional endoscopic treatment procedures can be both challenging and time-consuming to treat; and successful treatment can require a combination of techniques, including mechanical lithotripsy or extracorporeal shock-wave lithotripsy. We performed needle knife sphincterotomy and attempted to remove a CBD stone using biopsy forceps and alligator grasping forceps without a lithotripter in a patient with a large impacted stone at Vater's ampulla. After attempting several techniques, the stone was successfully removed with balloon extraction. PMID- 20590757 TI - Successful retrieval of an impacted mechanical lithotripsy basket: a case report. AB - We report the successful retrieval of an impacted mechanical lithotripsy basket. In a patient with two large common bile duct stones, the basket with the entrapped stone was impacted within the mid-common bile duct. We then attempted to use another mechanical lithotripter; however the central wire of the basket fractured at the handle portion. Grasping a few wires of the impacted basket with rat-tooth forceps allowed the wires of the basket to slip away from the stone. The present report describes the safe and effective use of rat-tooth forceps in the management of an impacted lithotripter basket. PMID- 20590758 TI - Case report: trouble-shooting for difficult cases of common bile duct stones with endoscopic treatment. AB - A case of basket catheter impaction was experienced during treatment for a common bile duct (CBD) stone. In cases of large CBD stones, mechanical basket lithotripsy or extracorporeal shock wave lithotripsy (ESWL) is usually carried out. However, once basket catheter impaction occurs, ESWL should be performed in the remaining basket catheter, which is passed through the patient's nose, and further ESWL basket lithotripsy must be carried out at a later time. On one occasion, a mechanical lithotripter was inserted along-side the conventional basket catheter through the incised papilla. This procedure is a safe and useful method for the clearance of CBD stones that cannot be removed with standard endoscopic procedures due to an impacted basket catheter. PMID- 20590759 TI - Is nasobiliary drainage unnecessary for drainage of acute suppurative cholangitis? Our experience. AB - Two randomized controlled trials comparing endoscopic nasobiliary drainage (ENBD) and internal endoscopic biliary drainage (internal EBD) for acute suppurative cholangitis (ASC) showed no significant difference in efficacy and both preferred internal EBD to ENBD. In this study, the necessity of ENBD was re-examined. Over five years, 59 patients underwent an emergency endoscopic procedure for ASC in our institute. If drainage was needed, we selected internal EBD as a first choice and ENBD was used in patients predicted to have early obstruction of the tube or retrograde infection of the bile duct. The rate of ENBD, for which reason ENBD was selected, and the efficacy of drainage were examined retrospectively. In the 59 patients, 40 patients had the stones completely removed without drainage, five internal EBD and two ENBD were performed without removal of stones and five internal EBD and seven ENBD were performed after removal of stones. In terms of white blood cell count and direct bilirubin level, no significant difference was observed between ENBD and internal EBD patients. ENBD was mainly selected for the patients with multiple biliary strictures, hemorrhage tendency and excessive purulent bile. Even though internal drainage is suitable in many ASC patients, ENBD is necessary in selected patients. PMID- 20590760 TI - Preliminary experience of a prototype forward-viewing curved linear array echoendoscope in a training phantom model. AB - Oblique-viewing curved linear array (OV-CLA) echoendoscopes have been widely used to perform endoscopic ultrasonography-guided fine needle aspiration and interventional endoscopic ultrasonography. Recently a prototype forward-viewing curved liner array (FV-CLA) echoendoscope was developed. In the present trial, 11 endoscopists participated in a hands-on trial and a questionnaire survey to evaluate the operation performance and visualization performance of a prototype FV-CLA scope in a phantom model designed for training of endoscopic ultrasonography. The results of our trial suggested that the FV-CLA scope is slightly inferior or equivalent to the conventional OV-CLA scope in operation performance, and that the FV-CLA scope is equivalent to the OV-CLA scope with regard to the visualization performance in a phantom model. PMID- 20590761 TI - Feasibility of interventional endoscopic ultrasound using forward-viewing and curved linear-array echoendoscope: a literature review. AB - Oblique-viewing curved linear-array echoendoscopes are widely used for interventional endoscopic ultrasound (EUS), not only for diagnostic but also for therapeutic procedures. Recently, development of a forward-viewing curved linear array echoendoscope (FV-ES) has been made. Several reports describe the usefulness of this new equipment for therapeutic interventional EUS, especially for pseudocyst drainage. A salient advantage of the FV-ES is that it enables the axial application of force during needle insertion and stenting. Furthermore, by attaching a cap device to the tip, the endoscope's capability can be expanded. Although the FV-ES has a narrower scanning range (90 deg) than that afforded by the oblique-viewing curved linear-array echoendoscope (180 deg), this characteristic reportedly does not hinder the performance of interventional EUS. The FV-ES might contribute to the advancement of interventional EUS. PMID- 20590762 TI - Current issues regarding endosonography-guided biliary drainage for biliary obstruction. AB - Transpapillary endoscopic biliary drainage is a well-accepted technique for patients with biliary obstruction. However, transpapillary access to the bile duct is not always possible, especially in patients with duodenal stenosis or difficult cannulation of the bile duct during endoscopic retrograde cholangiopancreatography. Percutaneous transhepatic biliary drainage or surgical bypass has been performed in cases of unsuccessful endoscopic retrograde cholangiopancreatography. Recently, endosonography-guided biliary drainage (ESBD) has been developed as a new biliary drainage technique. Current issues regarding ESBD are discussed in this article. Proper indications for ESBD should be established for widespread performance. Technical standardization and dedicated instruments for ESBD are also mandatory. PMID- 20590763 TI - Retrospective multicenter study concerning electrocautery forceps with soft coagulation for nonmalignant gastroduodenal ulcer bleeding in Japan. AB - Electrocautery forceps with soft coagulation are actively used for treatment of bleeding and nonbleeding visible vessels during endoscopic submucosal dissection, but the usefulness of gastroduodenal ulcer bleeding has not been elucidated so far. The purpose of this paper is to elucidate the outcomes of electrocautery forceps with soft coagulation for peptic and artificial gastroduodenal ulcer bleeding. A retrospective multicenter study of consecutive case series during one year involved nine departments of high-volume hospitals in Japan. The study included 128 consecutive patients (62 with peptic ulcers and 66 with artificial ulcers) with bleeding nonmalignant gastroduodenal ulcers that were revealed using emergency endoscopy between January 2008 and December 2008. Hemostasis was carried out using electrocautery forceps with soft coagulation. Rates of successful initial hemostasis, rebleeding, transfer to surgery, and death according to peptic and artificial ulcer bleeding were recorded. Successful initial endoscopic hemostasis was obtained in 61 peptic ulcer patients (98.4%) and 66 artificial ulcer patients (100%). Rebleeding was observed in seven peptic ulcer patients (11.5%) and five artificial ulcer patients (7.6%). Rates of successful management with endoscopic methods alone were 96.8% (60/62) and 100% (66/66) in peptic ulcer patients and artificial ulcer patients, respectively. There were no severe complications or deaths related to the management of gastroduodenal ulcer bleeding. The novel endoscopic method using electrocautery forceps with soft coagulation for gastroduodenal ulcer bleeding seems to provide safety and efficacy that is comparable with that of endoscopic hemostasis with other established hemostatic techniques. PMID- 20590764 TI - Bleeding peptic ulcers: the current management. AB - Bleeding peptic ulcer remains the commonest cause of emergency hospital admission worldwide and carries a mortality of up to 10%. Ulcer rebleeding is one of the important risk factors for mortality, and numerous strategies were examined to prevent ulcer rebleeding including the performance of scheduled second endoscopy and adjunctive proton pump inhibitor infusion. This article reviews the current management of bleeding peptic ulcer, including the prediction of clinical outcomes for bleeding peptic ulcer; the use of second-look endoscopy and adjunctive proton pump inhibitor infusion for prevention of rebleeding; and potential future development in achieving better primary endoscopic hemostasis with the use of endoscopic suturing. PMID- 20590765 TI - Multicenter questionnaire survey on the current situation of colorectal endoscopic submucosal dissection in Japan. AB - In order to understand the current use of endoscopic submucosal dissection (ESD) for the treatment of colorectal tumors in Japan, we administered a questionnaire survey to 1356 institutions all over the country. The subject of the survey was colorectal ESD performed from January 2000 to September 2008. Among the 1356 institutions, 391 (28.8%) responded to the questionnaire, and colorectal ESD was currently being performed in 194 institutions. The 194 institutions were almost equally distributed in Japan, that is, colorectal ESD has been performed all over the country. Among these 194 institutions, the procedure had been performed in 100 or more cases in 22 (11.3%) institutions and in 50-99 cases in 18 institutions (9.3%). The knives used in colorectal ESD were the Hook knife, Flush knife, and Flex knife. The average time required for colorectal ESD was 92.2 min, the rate of complete en bloc resection was 83.8%, the perforation rate was 4.8%, and no case of death from complications was reported. PMID- 20590766 TI - Endoscopic hemostasis of gastric ulcer bleeding by hemostatic forceps coagulation. AB - Endoscopic submucosal dissection (ESD) for early gastric carcinoma has been widely performed in Japan. In this technique, when hemorrhaging from vessels is observed, the bleeding point is coagulated using hemostatic forceps with the soft coagulation. There have been reports that using hemostatic forceps with soft coagulation is a safe and effective method of controlling upper gastrointestinal ulcer bleeding. However, there have been no reports regarding the comparative effectiveness of hemostatic forceps and clipping in upper gastrointestinal ulcer bleeding. Between April 2003 and December 2008, a total of 124 patients with gastric ulcer bleeding causing melena or hematochezia were treated with endoscopic hemostasis in our hospital. Two endoscopic hemostatic methods were used for different groups of patients: coagulation with hemostatic forceps was used for Group A and clipping was used for Group B. The rate of additional treatment required after the initial procedure was 28.6% (8/28) for Group A and 79.2% (76/96) for Group B, indicating a significantly lower rate for Group A than that for Group B (P < 0.01). Additional treatment consists of a hypertonic saline epinephrine injection. The rebleeding rate was 3.6% (1/28) for Group A and 8.3% (8/96) for Group B, again indicating a lower rate for Group A than for Group B. Finally, successful endoscopic hemostasis was 100% in both groups. Using the soft coagulation mode of hemostatic forceps is shown to be a safe, easy and effective method of controlling gastric ulcer bleeding in relation to clipping. PMID- 20590767 TI - Current status of endoscopic management for nonvariceal upper gastrointestinal bleeding. AB - Endoscopic hemostasis is widely performed for nonvariceal upper gastrointestinal (UGI) bleeding. As the aged Japanese population rapidly increases, the number of patients experiencing complications increases. The aim of this study was to evaluate the recent results of endoscopic hemostasis for nonvariceal UGI bleeding. A retrospective analysis of patients who underwent endoscopic procedures for nonvariceal UGI bleeding was performed. We performed 223 endoscopic procedures on 217 patients between January 1995 and July 2000, and 238 endoscopic procedures on 236 patients between January 2006 and September 2009 at the Kyoto Second Red Cross Hospital. We divided the patients into the 1995-2000 group and the 2006-2009 group. Patient characteristics, hemostasis methods chosen, rates of temporary hemostasis and rebleeding, and mortality were analyzed. There were many serious and actively bleeding cases in the 2006-2009 group (P < 0.001). The endoclip method and intravenous proton pump inhibitor were mainly used in the 2006-2009 group compared with the drug-injection method and intravenous H2 receptor antagonist in the 1995-2000 group (P < 0.001). Through these treatments, the two groups were able to obtain similar treatment outcomes. Through the progress of endoscopic management we obtained similar satisfactory results in the 2006-2009 group, which had multiple complicated cases, compared to the 1995-2000 group. PMID- 20590768 TI - Present state of endoscopic hemostasis for nonvariceal upper gastrointestinal bleeding. AB - The subjects of this study were 208 patients who underwent endoscopic hemostasis at the Department of Gastroenterology and Hepatology, Iwate University between January 2004 and December 2008. There were 153 men and 55 women with a mean age of 65.3 years. Among them, 181 patients underwent endoscopic hemostasis in the stomach or duodenum and were divided into the peptic ulcer and artificial ulcer groups. The following were retrospectively analyzed: success rates of endoscopic hemostasis, rates of rebleeding, and devices used during treatment. The overall success rate of endoscopic hemostasis was 97.2%. Hemostasis was achieved in 98.2% of the cases with peptic ulcer bleeding and in 88.9% of the cases with artificial ulcer bleeding. Monotherapy (one hemostatic device) was used in 141 cases (77.9%), combination therapy (multiple hemostatic devices) was used in 39 cases (21.5%), and primary hemostasis was used in one case (0.6%) because of blood flow reduction during the observation period. A heat probe was used in 145 cases (80.1%), making it the most frequently used device. Endoscopic hemostasis is very effective for nonvariceal upper gastrointestinal bleeding. PMID- 20590769 TI - Surgical indications and procedures for bleeding peptic ulcer. AB - Recent important insights into the surgical treatment of bleeding peptic ulcer are reviewed in this article. Although the widespread use of endoscopic treatment and interventional radiology has reduced the number of surgical cases, surgery still plays a pivotal role in managing bleeding peptic ulcer. Failure to stop the bleeding by endoscopy and/or interventional radiology is the most important indication for emergency surgery. An early elective/planned surgery after the initial endoscopic control to prevent life-threatening rebleeding seems justified in patients who have risk factors for rebleeding, although its true efficacy still remains controversial. The surgical procedures in emergency situations should be limited to safe hemostasis. The addition of acid-reduction surgery may be unnecessary as a result of the increasing utilization of proton pump inhibitors. Angiographic embolization may be a less invasive alternative to surgery, and may further enhance endoscopic hemostasis. PMID- 20590770 TI - Indications for endoscopic resection of colorectal polyps and surveillance guidelines. AB - We report three keynote lecture presentations from the Endoscopic Forum Japan 2009 at Otaru, Hokkaido, on 1-2 August 2009. We will discuss herein: (i) colorectal cancer screening focusing on a comparison between the National Polyp Study and the Japan Polyp Study; (ii) how to deal with small polyps <5 mm in diameter; (iii) the natural history of colorectal tumor development; (iv) the importance of follow up for local recurrence after endoscopic resection for colorectal polyps; and (v) screening for colorectal cancer using two new modalities, narrow-band imaging and autofluorescence imaging. A questionnaire was completed by everyone involved in the conference and the most important results were reported and then discussed by the participants. PMID- 20590771 TI - Natural history of small colorectal protuberant adenomas. AB - Most previous studies of the natural history of small colorectal adenomas showed no increase in size, no changes that would have necessitated treatment within a couple of years and that malignant transformation is rare. Using endoscopic follow up for a mean period of 43.1 months we assessed the development and progression of 408 protuberant adenomas that were under 10 mm in diameter. Of the 408 lesions, 22 (5.4%) underwent morphological changes. There were 12 lesions (2.9%) whose final tumor diameter had reached 10 mm or more. There were three lesions (0.7%) that developed and progressed into intramucosal cancer. We concluded from the literature and from our own results that small colorectal protuberant adenomas do not grow to advanced adenomas within 5 years. PMID- 20590772 TI - Surveillance colonoscopy using a transparent hood and image-enhanced endoscopy. AB - Colonoscopists can miss adenomas during colonoscopy screening. A transparent hood attached to the tip of the colonoscope helps detection of colorectal adenomas, but as far as we are aware, there has been no trial indicating its statistically significant effectiveness. Total colonic dye spray might improve the adenoma detection rate but it is complicated and time-consuming for routine clinical usage. Moreover, the efficacy of narrow band imaging for detection of colorectal adenoma is controversial and is still under debate. Autofluorescence imaging (AFI) might be better able to detect flat lesions than white light imaging (WLI), but its ability is influenced easily by the area of the observation. Therefore, we have attached a transparent hood to the tip of an AFI colonoscope during colonoscopy screening in clinical usage. AFI can detect a flat lesion, which is difficult to detect using WLI. A transparent hood can help to detect lesions behind the folds by pushing the colonic fold. We expect that mounting a transparent hood would work complimentary to AFI. Further improvements, including a combination of AFI and a transparent hood, are needed and they would provide optimal surveillance intervals. PMID- 20590773 TI - Impact of narrow-band imaging in screening colonoscopy. AB - Narrow band-imaging (NBI) enhances mucosal visualization of the vascular network and surface structure and helps to increase the visibility of neoplasia by improving contrast. Studies on the detectability of colorectal neoplastic lesions using NBI have primarily been reported in Western countries, but the published opinions and conclusions remain controversial at the present time. Our earlier prospective pilot study demonstrated that NBI colonoscopy significantly improved detection of flat lesions, which are more likely to be missed, particularly on the right side of the colon. It is especially important that even examiners performing routine screening colonoscopies become sufficiently familiar with flat and depressed lesions and then take full advantage of the endoscopic systems and specific image enhancement functions currently available for improved detection of flat and diminutive lesions. Adequate bowel preparation is another important consideration. PMID- 20590774 TI - Prevalence and clinicopathological features of nonpolypoid colorectal neoplasms: should we pay more attention to identifying flat and depressed lesions? AB - Flat and depressed (nonpolypoid) colorectal lesions have been described for over two decades by Japanese investigators. These neoplastic lesions are typically smaller than polypoid ones and can be more difficult to identify during screening colonoscopy. In particular, depressed type colorectal lesions are usually small in size, with a number of studies showing them to be at greater risk for developing high-grade dysplasia or submucosal invasive cancer. It has also been suggested that they may follow a different carcinogenic pathway to flat elevated or protruding adenomas. This paper summarizes recent data of nonpolypoid colorectal neoplasms from Western and Asian countries. PMID- 20590775 TI - Local recurrence and surveillance after endoscopic resection of large colorectal tumors. AB - Local recurrence rates after endoscopic piecemeal mucosal resection (EPMR) typically range from 10 to 23%. In our previous study, the local recurrence rate after a piecemeal resection was significantly higher than that after an en bloc resection, irrespective of tumor size or macroscopic features. To reduce local recurrence after an EPMR, it is important to carefully note the circumferences of the edge and base of the ulcer. Recently, endoscopic submucosal dissection (ESD) was developed and recognized for its effectiveness in large, complete, en bloc resections and precise pathological assessments. ESD also showed lower local recurrence rates, ranging from 0 to 3% in previous, retrospective studies. However, ESD showed a higher perforation rate and longer procedure times; thus, it is necessary to improve ESD. An appropriate surveillance interval after EPMR was still controversial, and recommendations of some guidelines ranged from 2 to 9 months. In order to determine the appropriate interval, a randomized controlled study is necessary. PMID- 20590776 TI - Endoscopic management of bile duct stones. AB - Endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) are endoscopic techniques that are used for the removal of bile duct stones. Although EST and EPBD have become established techniques, occasionally the management of bile duct stones may be difficult in cases of large stones, multiple stones, and tapering or tortuosity of the distal common bile duct. In such patients, extracorporeal shock wave lithotripsy, mechanical lithotripsy or electrohydraulic lithotripsy, laser lithotripsy, or surgical intervention may be necessary. Furthermore, recently EST plus a large papillary balloon dilation has been popular for the treatment of difficult bile duct stones. Currently, endoscopic lithotripsy for bile duct stones seems to be a promising standard technique. PMID- 20590777 TI - Management of the bile duct stone: current situation in Japan. AB - Endoscopic treatment is now recognized as the standard treatment for common bile duct stones worldwide. Endoscopic treatment routinely involves endoscopic sphincterotomy in most countries including Japan and endoscopic papillary balloon dilation is also a widely used alternative to endoscopic sphincterotomy in Japan. Surgery in any form, including laparoscopic surgery, is mainly performed when endoscopic treatments are unsuccessful or unfavorable. Other therapeutic modalities considered under certain circumstances include lithotripsy under the guidance of percutaneous transhepatic cholangioscopy, peroral cholangioscopy, or enteroscopy; electrohydraulic lithotripsy or laser lithotripsy; and extracorporeal shock-wave lithotripsy. PMID- 20590778 TI - Alternative methods in the endoscopic management of difficult common bile duct stones. AB - The endoscopic method is accepted as a first treatment modality in the management of extrahepatic bile duct. Most large stones can be removed with basket and mechanical lithotripsy after endoscopic sphincterotomy. Currently, in treating large extrahepatic bile duct stones, endoscopic papillary large balloon dilation with mid-incision endoscopic sphincterotomy is actively performed instead of applying mechanical lithotripsy after full endoscopic sphincterotomy. Herein, we describe the conceptions, proper indications, methods and complications of endoscopic papillary large balloon dilation with regards to currently published reports. In addition, intracorporeal lithotripsy by peroral cholangioscopy with an ultra-slim upper endoscope is introduced, which is more convenient than previous conventional intracorporeal lithotripsy methods using mother-baby endoscopy or percutaneous transhepatic cholangioscopy. Lastly, biliary stenting with the choleretic agent administration method is briefly reviewed as an alternative treatment option for frail and elderly patients with large impacted common bile duct stones. PMID- 20590779 TI - Evaluation of residual bile duct stones by peroral cholangioscopy in comparison with balloon-cholangiography. AB - We evaluated the usefulness of peroral cholangioscopy (POCS) for residual bile duct stones in patients with complete bile duct clearance confirmed by balloon occluded cholangiography. A total of 108 patients with common bile duct stones who underwent POCS after extraction of stones via endoscopic sphincterotomy, resulting in complete bile duct extraction confirmed by balloon-occluded cholangiography, were retrospectively evaluated. For the treatment of difficult stones, stones were fragmented by mechanical lithotripsy (ML) or electrohydraulic lithotripsy (EHL). In 26 patients (24%), residual stones were detected with POCS in the lower bile duct. In patients with residual stones, large bile duct stones, juxtapapillary diverticulum, and use of ML or EHL were significantly related to residual stones (P < 0.05). Although a prospective study is necessary to clarify whether this procedure is appropriate in aspects of cost and benefits, POCS appears to be a useful diagnostic tool for confirming complete extraction of bile duct stones. POCS may be useful, particularly when lithotripsy using ML or EHL is performed and a large pneumobilia exists in the bile duct. PMID- 20590780 TI - Current managements and outcomes of peptic and artificial ulcer bleeding in Japan. AB - The recent trend of gastroduodenal ulcer bleeding in Japan has not been elucidated in detail and the data for a new categorized type, artificial ulcer bleeding, is completely lacking. The purpose of this paper is to elucidate current managements and outcomes of peptic and artificial ulcer bleeding in Japan. A retrospective multicenter study of consecutive case series was carried out during one year at nine departments of high-volume hospitals in Japan. The study included 325 consecutive patients (239 with peptic ulcers and 86 with artificial ulcers) with bleeding nonmalignant gastroduodenal ulcers that were revealed by emergency endoscopy between January 2008 and December 2008. Hemostasis was carried out mainly using endoscopic treatments. Rates of successful initial hemostasis, rebleeding, transfer to surgery, and death were recorded according to peptic and artificial ulcer bleeding. Additionally, preferred endoscopic methods, concomitant use of antisecretory drugs, and timing of second-look endoscopy were also measured. A total of 227 (99.1%) of 229 peptic ulcer patients with endoscopic treatment and all (100%) 84 artificial ulcer patients underwent successful tentative hemostasis. Rebleeding occurred in 23 peptic ulcer patients (10.1%) and 10 artificial ulcer patients (11.9%). One peptic ulcer patient and two artificial ulcer patients had final surgical rescue due to rebleeding. No death was observed. Monotherapy was predominant (around 65% of cases) in both types of ulcers. The coagulation forceps method was more frequently applied in artificial ulcers (P < 0.05). A per oral proton pump inhibitor was more frequently used in artificial ulcers (P < 0.05), although an intravenous proton pump inhibitor was used in the majority of patients in both types of ulcers. The frequency of second-look endoscopy in peptic ulcers (88%) was significantly higher than that in artificial ulcers (71%) (P < 0.05). There seemed to be no rule as to the timing of second-look endoscopy, although it was most frequently performed on the day after hemostasis. The recent outcomes of endoscopic treatment for nonmalignant gastroduodenal bleeding in Japan were excellent in both peptic and artificial ulcers with similar efficacies. Although they were minor findings, some differences in applied endoscopic methods, concomitant use of antisecretory drugs, and presence of second-look endoscopy were observed. PMID- 20590781 TI - Endoscopic treatment of difficult common bile duct stones. AB - Recent developments in treatment devices and advancements in technology have made endoscopic treatment the first choice for bile duct stones. In endoscopic treatment, the stones are removed after expanding the papilla with endoscopic sphincterotomy or endoscopic papillary balloon dilatation. The devices used to remove bile duct stones include basket catheters, balloon catheters and mechanical lithotripters, and their employment varies depending on the clinical situation. Stone removal by endoscopy is superior to other options, although treatment can be difficult in some cases. The reasons are mainly large stones, a history of gastric surgery, and Mirizzi syndrome. For such difficult cases, various adjuvant treatments such as extracorporeal shock wave lithotripsy, electrohydraulic lithotripsy and lasers are recommended rather than using just a mechanical lithotripter. Recently, large-diameter biliary orifice balloon dilation, a method in which the papilla is expanded using a large-diameter balloon, allowing the stones to be removed, has been reported and is attracting increasing attention. PMID- 20590782 TI - Large balloon papillary dilation for removal of bile duct stones in patients who have undergone a billroth ii gastrectomy. AB - Extraction of large bile duct stones in patients who have undergone a Billroth II (B-II) gastrectomy can be challenging. Recently, a large balloon dilation performed after endoscopic sphincterotomy (ESLBD) was useful for the removal of large bile duct stones. The aim of our study was to evaluate the feasibility and safety of ESLBD for removal of bile duct stones in patients who have undergone a B-II gastrectomy. ESLBD for removal of bile duct stones were performed in 11 patients with a B-II gastrectomy at Tokyo Medical University Hospital. Immediately after EST, a large balloon catheter (maximum diameter 15 mm, 18 mm, or 20 mm) was passed over the guide-wire and positioned across the main duodenal papilla. Maximum stone size (short diameter) ranged from 7 to 30 mm with a median of 13.5 mm. The number of stones was 1-26 with a median of 4.8. The common bile duct diameter was 10 mm to 30 mm with a median of 18.1 mm. A mechanical lithotripter for crushing stones was used in two patients (18%). Papillary balloon dilation using variously sized balloons was performed in addition to endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in all cases at one session. There were no procedure-related adverse events such as acute pancreatitis or retroperitoneal perforation. ESLBD appears to be an effective and safe treatment for removal of difficult bile duct stones in patients who have undergone a B-II gastrectomy. PMID- 20590783 TI - The effect of nightshift on emergency registrars' clinical skills. AB - OBJECTIVE: The effect of nightshift on ED staff performance is of clinical and risk-management significance. Previous studies have demonstrated deterioration in psychomotor skills but the present study specifically assessed the impact of nightshift on clinical performance. METHODS: The ED registrars in a tertiary hospital were enrolled in a prospective observational study and served as their own controls. During nightshift, subjects were presented simulated scenarios and tested with eight clinical questions developed to Fellowship examination standard. Matched scenarios and questions for the same subjects during dayshift served as controls. Two investigators, blinded to subject identity and the setting in which questions were attempted, independently collated answers. RESULTS: Of 22 eligible subjects, all were recruited; four were excluded owing to incomplete data. A correlation of 0.99 was observed between the independent scoring investigators. Of a possible score of 17, the median result for nightshift was 9.5 (interquartile range: 8-11); corresponding value for dayshift was 12 (interquartile range: 10-13); P = 0.047. CONCLUSION: Nightshift effect on clinical performance is anecdotally well known. The present study quantifies such effects, specifically for the ED setting, and paves the way for focused research. The implications for clinical governance strategies are significant, as the fraternity embraces the mandate to maintain quality emergency care 24 h per day. PMID- 20590784 TI - Use of sterile saline as a conduction agent for ultrasound visualization of central venous structures. AB - OBJECTIVE: To determine whether sterile saline as a conduction agent provides adequate visualization of anatomic structures to attempt ultrasound-guided vascular access. METHODS: This prospective study involved a convenience sample of adult patients (18 years and older) who presented to an urban academic ED during a 3-month study period. Each patient had three six-second ultrasound video clips obtained of the right internal jugular vein and surrounding structures utilizing three different conduction agents, water-based gel (the control), sterile saline or no conduction agent. Video clips were randomized and assigned a numeric code to blind reviewers to the conduction agent. They were then independently reviewed by two experts who determined whether anatomic structures were visualized with enough detail to perform ultrasound-guided vascular access. The reviewers also rated the overall image quality of each video clip using a 100 mm visual analogue scale (VAS). RESULTS: Forty-seven patients were included in the final analysis. The raw agreement was 100% (95% confidence intervals [CI]: 93-100%) with a kappa of 1.0 between the two reviewers in assessing whether they would be able to perform vascular access using the images obtained using saline as a conduction agent. The median VAS for gel across both reviewers was 92 (95% CI: 90-93) and the median VAS differences for saline and no medium were -3 (95% CI: -1 to -3) and -46 (95% CI: -22 to -61), respectively. CONCLUSIONS: The use of sterile saline as a conduction agent allows adequate visualization of anatomic structures to attempt ultrasound-guided vascular access. PMID- 20590785 TI - Manipulation of nasal fractures with local anaesthetic: a 'how to do it' with online video tutorial. AB - Nasal fractures are the most common facial fractures and displaced fractures may cause considerable cosmetic concern. Traditionally, displaced nasal fractures have been manipulated under general anaesthesia (GA) performed within 2 weeks of the injury. Despite evidence for the benefit of local anaesthesia (LA), nasal fractures are still most commonly reduced under GA. We have presented a method of reduction of simple nasal fractures under LA in an outpatient setting. This has the advantage of being painless, simple to attempt and cost-effective. If reduction is inadequate then a general anaesthetic reduction is still possible. A recent comprehensive systematic review of all the available evidence did not show any significant difference (in terms of cosmesis, pain or nasal obstruction) between using LA and GA methods and highlighted the evidence base to support LA. We describe our method of assessment and treatment of displaced nasal fractures and provide an online tutorial (http://sciencestage.com/v/22194/local-anaesthetic nasal-fracture-reduction.html). It is important to keep in mind that any concerns should be referred to an otolaryngology specialist for further management and that practitioners attempting this technique should first receive training from an otolaryngologist. PMID- 20590786 TI - Morbidity associated with heroin overdose presentations to an emergency department: a 10-year record linkage study. AB - INTRODUCTION: To examine hospitalizations in a cohort of 224 patients who presented with non-fatal heroin overdose to an ED. METHODS: A record linkage study, using the morbidity, mental health and mortality databases in the Data Linkage Unit of the Department of Health, Western Australia. The main outcome measures were hospital separations 5 years before and after entry into the cohort. RESULTS: Before entry into the cohort, 199 (89%) patients had an admission to mental health services. These 199 had a combined total of 1367 separations, most commonly for a mental health condition, injury or poisoning. Women had more than twice the relative risk (RR) of men for all separations (RR 2.35, 95% confidence interval [CI] 1.96-2.82, P < 0.001) and for injury and poisoning separations (RR 2.04, 95% CI 1.56-2.66, P < 0.001). The highest concentrations of separations occurred within 1 year before and 1 year after entry into the cohort. There were 12 (5.4%, 95% CI 2.9-9.4%) deaths, most commonly from overdose. CONCLUSION: Non-fatal heroin overdose ED presentations are associated with a cluster of hospitalizations around that episode, likely to be related to heroin availability. Presentation to hospital by heroin users represents an opportunity to counsel less risky behaviour. PMID- 20590787 TI - Acute neck swelling: a diagnostic dilemma in a regional hospital. AB - This case study describes an incident of acute neck swelling in a patient presenting to the ED of a regional hospital after hours. Maintaining and securing her airway proved to be challenging, as did arriving at the correct cause of her airway obstruction and neck swelling. PMID- 20590788 TI - Suprapubic catheter displacement: a forgotten phenomenon. AB - Suprapubic catheters provide a durable form of long-term bladder drainage. Few cases of catheter displacement have been reported. We report a series of three patients with suprapubic catheter displacement following catheter changes, with varying clinical presentations and sequelae. Early suspicion of catheter displacement in patients with suprapubic catheters presenting with undiagnosed sepsis or abdominal pain, can lead to timely radiological diagnosis and treatment. PMID- 20590789 TI - Abdominal pain due to rectus abdominis muscle haematoma associated with anticoagulant therapy. PMID- 20590790 TI - In response: Review article: The use of pelvic examination within the emergency department in the assessment of early pregnancy bleeding. PMID- 20590792 TI - Abstracts from the 9th European Congress on Epileptology. Rhodes, Greece. June 27 July 1, 2010. PMID- 20590800 TI - Dystonia Europe: Hamburg 2008. Foreword. PMID- 20590801 TI - Differential diagnosis of dystonia. AB - Dystonia is a movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements and abnormal postures. Diagnosing dystonia may be difficult, because of variability of dystonia presentation, uncertain recognition of the specific clinical signs, wide etiological spectrum, and coexistence of other movement disorders. The major difficulties in the diagnostic assessment of primary and non-primary dystonia derive from its confusion with other movement disorders or with a psychogenic disorder. The clinical heterogeneity of dystonia and some examples of misdiagnosis are reviewed here. The movement disorders that can be most commonly taken for dystonia are tremor, Parkinson's disease, myoclonus, chorea, and tics. Given the occurrence of confounding factors, along with specific genetic and laboratory test, it is of great importance to apply a specific algorithm to recognize the clinical signs of dystonia. PMID- 20590802 TI - The epidemiology of primary dystonia: current evidence and perspectives. AB - The number of existing cases of primary dystonia in the population is not precisely known, but the condition is probably much more frequent than reported. By minimum prevalence estimates, primary dystonia should be considered the third most frequent movement disorders after essential tremor and Parkinson's disease. The most likely etiologic scenario suggested by epidemiological data is that primary dystonias are products of a genetic background and an environmental insult. Current information on the causation of primary dystonia, late-onset dystonia in particular, is often unreliable because of methodological problems inherent to case-control investigation and to the heterogeneity of dystonia. To expand our knowledge on dystonia, we need to design population-based studies, to perform association studies taking into account the heterogeneity of dystonia, and to collect exhaustive clinical data in a standardized and reliable way. PMID- 20590803 TI - Craniocervical dystonia: clinical and pathophysiological features. AB - Blepharospasm, oromandibular, lingual, laryngeal and cervical dystonia are common forms of adult-onset dystonia. Each condition may appear in isolation or manifest along with other forms of craniocervical dystonia. Although the various craniocervical dystonias typically present with involuntary muscle spasms causing abnormal postures, they differ for some clinical features. Neurophysiologic and neuroimaging studies have shown a number of motor and sensory abnormalities at cortical and subcortical levels, probably reflecting a dysfunction in the basal ganglia-thalamo-cortical circuits. The best treatment for craniocervical dystonia is botulinum toxin injected into the overactive muscles. PMID- 20590804 TI - Focal limb dystonia. AB - Limb dystonia (LD) refers to dystonia affecting one arm or leg. Depending on the site of onset, age at onset, and the etiology, progression and prognosis will be different. Usually young-onset primary dystonia affects the lower limbs and tends to generalize, while in adult-onset, it appears in the arm and remains focal. Lower limb dystonia in adults is rare as a primary cause, and parkinsonism or other neurological diseases must always be ruled out. In the text that follows, we review the main clinical features of the primary and secondary limb dystonias considering the age at onset and etiology. PMID- 20590805 TI - Spasmodic dysphonia and botulinum toxin: experience from the largest treatment series. AB - Spasmodic dysphonia is a focal laryngeal dystonia, with adductor, abductor, mixed, respiratory and singer's types. Our series over 24 years includes 1300 patients. 82% are of the adductor type; 63% were female; 12% had a positive family history and 82.4% had a focal distribution. All of the patients were managed with varying degrees of success with individualised dosing of botulinum neurotoxin A injected into the laryngeal musculature under EMG guidance. PMID- 20590806 TI - Focal dystonia in musicians: phenomenology, pathophysiology and triggering factors. AB - BACKGROUND: Musician's dystonia is a task-specific movement disorder that manifests itself as a loss of voluntary motor control in extensively trained movements. In many cases, the disorder terminates the careers of affected musicians. Approximately, 1% of all professional musicians are affected. The pathophysiology of the disorder is still unclear. Findings include: (i) reduced inhibition in different levels of the central nervous system, (ii) maladaptive plasticity, e.g. in the somatosensory cortex and in the basal ganglia and (iii) alterations in sensorimotor processing. METHODS: Review of the literature. RESULTS: Epidemiological data demonstrated a higher risk for those musicians who play instruments requiring maximal fine-motor skills. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely used hand. In psychological studies, musicians with dystonia had more perfectionist tendencies than healthy musicians. These findings strengthen the assumption that behavioural factors may be involved in the etiology of musician's dystonia. Hereditary factors may play a greater role than previously assumed. CONCLUSIONS: We propose a heuristic model that may explain the relatively high incidence of focal dystonia in musicians. This model assumes the coactions between a predominantly genetically determined predisposition and intrinsic and extrinsic triggering factors. PMID- 20590807 TI - Dystonia-plus syndromes. AB - Dystonia-plus syndromes represent a heterogeneous group of diseases, where dystonia is accompanied by other neurological features and gene mutations can be detected frequently. Symptomatic dystonias and complex neurodegenerative diseases with dystonia as part of the clinical presentation are excluded from this category. At present, the following disorders are categorized as dystonia-plus syndromes: Dopa-responsive dystonia (DRD) is a mostly pediatric-onset, neurometabolic disorder with two different modes of inheritance: in its autosomal dominant form, heterozygous mutations of GTP-cyclohydrolase I (GCH1, DYT5) cause DRD with reduced penetrance and excellent and lasting response to levodopa. Autosomal-recessive (AR) forms of DRD are caused by homozygous or compound heterozygous mutations of the tyrosine hydroxylase (TH) or the sepiapterin reductase (SPR) gene. In AR-DRD, the phenotype is generally more severe including cognitive deficits and developmental delay. Diagnosis can be confirmed by analysis of CSF pterine metabolites. Alternatively, comprehensive genetic testing yields causative mutations in up to 80% of patients. Myoclonus-dystonia (M-D) is caused by heterozygous mutations of the epsilon-sarcoglycan gene (SGCE). Dystonia is generally only mild to moderate, and 'lightning-like' myoclonic jerks occur rarely at rest and can be triggered by complex motor tasks like writing and drawing. Both features together with an age at onset below 25 years strongly predict SGCE mutation in M-D and differentiate this genetic disease from other 'jerky' dystonias. The combination of dystonia and parkinsonism can only be rarely observed in non-degenerative syndromes. Besides DRD, two additional syndromes have been classified. Rapid-onset dystonia-parkinsonism (RPD, DYT12) is a rare disorder with an abrupt onset of symptoms over minutes to days, prominent bulbar involvement and parkinsonism with a lack of response to levodopa. Patients with this rare phenotype should be screened for mutation in the Na(+)/K(+) ATPase alpha3-subunit (ATP1A3) gene, even if family history is negative. Recently, a novel form of dystonia-parkinsonism (DYT16) has been found to be linked to mutations in the PRKRA gene, whose relation to basal ganglia disorders is yet unknown . PMID- 20590808 TI - Dystonia. The paediatric perspective. AB - BACKGROUND AND AIMS: This review focuses on some paediatric dystonias such as transient dystonias, new primary paediatric-onset dystonias, dopamine biosynthesis defects and new paroxysmal disorders. It is designed to provide practical help for neurologists and neuropediatricians to make appropriate diagnoses and plan the management of these disorders. MATERIAL AND METHODS: Literature searches were performed and original papers, meta-analyses and review papers were reviewed. CONCLUSION: Paediatric onset dystonia is an increasingly interesting group of conditions that provides an expanding area of neuroscientific knowledge. Given the long life expectancy of children, appropriate treatment at the correct moment will have an important, lasting effect on the personal, social and healthcare domains. PMID- 20590809 TI - Secondary dystonia--clinical clues and syndromic associations. AB - Dystonic syndromes can be divided into primary and secondary forms. Diagnosis of secondary dystonic syndromes can be challenging as causes are multifold. They include brain lesions of various origins, metabolic disease, neurodegenerative conditions, or following exposure to drugs or toxins. However, characteristic investigational findings may be directive in the diagnostic process and facilitate making the correct diagnosis and thus allow initiating the ideal treatment. In this article, we point out some clinical clues and syndromic associations which may be helpful in the approach to a patient with dystonia. PMID- 20590811 TI - The role of genes in causing dystonia. AB - BACKGROUND: In recent years, the identification of several new dystonia genes has provided important insights into the nature of this clinically and genetically heterogeneous disorder. AIMS: To identify the role of genes in the pathophysiology of dystonia. MATERIALS AND METHODS: Literature review from 1985 to 2009. RESULTS: Early-onset dystonia is overall rare, often monogenic and tends to spread to become generalized. In contrast, adult-onset dystonia is relatively common, typically sporadic and usually remains focal. To date, 19 different forms of monogenic dystonia (primary dystonias and dystonia-plus syndromes) have been identified and classified as DYT loci. Likewise, secondary dystonia is a feature of a large number of hereditary conditions, such as Wilson disease or neuroacanthocytosis. This review focuses on the eight monogenic primary dystonias, six of which are associated with an early-onset generalized phenotype (DYT1, 2, 4, 6, 16 and 17), while the remaining two are characterized by an adolescent- or adult-onset focal or segmental form of dystonia (DYT7 and 13). DISCUSSION: Primary dystonias have a strong genetic component that is most obvious in the rare monogenic early-onset generalized forms. However, genetic risk factors also are likely to play an important role in the pathophysiology of the much more common late-onset focal and segmental primary dystonias. CONCLUSION: The identification of these genetic factors is a critical future aim in dystonia research. PMID- 20590812 TI - On muscle spindles, dystonia and botulinum toxin. AB - Dystonia may produce co-contractions and constant strain in numerous muscle fibers, including those of the muscle spindles. As proprioceptors, muscle spindles detect dynamic or static changes in muscle length and their afferent projections to the spinal cord play a central role in control of antagonistic muscles. Their parallel arrangement with extrafusal muscle fibers and association with the earlier recruited oxidative motor units allow them to conveniently sample the activity of all motor units and effectively modulate movement. At the same time, fusimotor muscle spindle innervation contracts the striated polar portions of the intrafusal muscle fibers and prevents their slackening during extrafusal muscle contractions. Botulinum toxin remains the most efficient therapy of dystonia. Its muscular mechanism of action is hinged on cholinergic blockade not only of extrafusal, but also of intrafusal muscle fibers. Besides being a targeted muscular therapy, the alteration of the corresponding sensory input following an effect of botulinum toxin on the intrafusal muscle fibers is pivotal in modulating loss of pre-synaptic inhibition in dystonia, including suppression of the tonic vibration reflex. Whether or not trans-synaptic botulinum toxin migration occurs, a modification of the central motor programming is bound to happen in dystonia, with botulinum toxin acting either as another 'sensory trick' or as a form of 'short-term plasticity'. Knowledge of the muscle spindle anatomy and function is key to unify our understanding of abnormal movements and of effects of botulinum toxin therapy. Thus, in dystonia, overactivity of muscles and increased spindle sensitivity are germane to botulinum toxin targets of action. PMID- 20590810 TI - Functional imaging in hereditary dystonia. AB - BACKGROUND: Impaired cortical inhibiton and maladaptive cortical plasticity are functional hallmarks of sporadic focal dystonias. Whether or not these mechanisms translate to generalized dystonias and whether these features reflect state or trait characteristics are topics of research in hereditary dystonias. METHODS: We present a series of studies using a multitracer approach with positron emission tomography (PET) and diffusion tensor MRI (DTI) in the DYT1 and the DYT6 genotype. RESULTS: In these hereditary dystonias functional and microstructural abnormalities were found in cortico-striatal-pallido-thalamocortical (CSPTC) and cerebellar-thalamo-cortical circuits. Genotype-specific abnormalities were localized to the basal ganglia, SMA and cerebellum. Functional changes, as potential correlates of maladaptive sensorimotor plasticity were found throughout the sensorimotor system and were more pronounced in affected mutation carriers than in their non-manifesting counterparts. In both genotypes, striatal metabolic abnormalities were paralleled by genotype-specific reductions in D(2) receptor availability. However, these reductions failed to show a clear association with clinical or functional markers of the disease. By contrast, microstructural changes of cerebellar pathways clearly related to penetrance and may thus represent the main intrinsic abnormality underlying cortical downstream effects, such as increased sensorimotor responsivity. CONCLUSIONS: These studies are consistent with the view of primary torsion dystonia as a neurodevelopmental circuit disorder involving CSPTC and related cerebellar pathways. PMID- 20590813 TI - The role of torsinA in dystonia. AB - DYT1 dystonia is an autosomal-dominant movement disorder, characterised by early onset of involuntary sustained muscle contractions. It is caused by a 3-bp deletion in the DYT1 gene, which results in the deletion of a single glutamate residue in the C-terminus of the protein torsinA. TorsinA is a member of the AAA ATPase family of; chaperones with multiple functions in the cell. There is no evidence of neurodegeneration in DYT1 dystonia, which suggests that mutant torsinA leads to functional neuronal abnormalities leading to dystonic movements. In the recent years, different functional roles have been attributed to torsinA, including being a component of the cytoskeleton and the nuclear envelope, and involvement in the secretory pathway and synaptic vesicle machinery. The aim of this review is to summarise these findings and the different models proposed, which have contributed to our current understanding of the function of torsinA. PMID- 20590814 TI - Botulinum toxin for treatment of dystonia. AB - Botulinum toxin (BT) is used in various medical specialties. However, dystonia is still one of the most important indications for BT therapy. BT drugs consist of botulinum neurotoxin, complexing proteins and excipients. Botox, Dysport and Xeomin are BT type A drugs and produce similar therapeutic and adverse effects (AE). Neurobloc/MyoBloc is based upon BT type B. Its use is limited by substantial systemic anticholinergic AE. The potency of BT drugs may be compared as follows: Botox:Xeomin:Dysport:Neuobloc/MyoBloc = 1:1:3:40. BT selectively blocks the cholinergic innervation of striate and smooth muscles and exocrine glands. It can produce obligate, local and systemic AE. However, its overall AE profile including long-term safety is excellent. BT can be blocked by antibodies. Risk factors include single doses, interinjection intervals and the immunological quality of the BT drug applied. Planning of BT therapy is based upon target muscle identification and estimation of their dystonic involvement. For planning of BT therapy and BT placement, electromyography and imaging techniques may be used additionally. So far, total Xeomin and Botox doses of up to 840 MU have been used without clinically detectable systemic AE. BT can be used to treat focal dystonias including cranial, pharyngolaryngeal, cervical and limb dystonias. In segmental and generalized dystonias, BT therapy has to be focussed on the most relevant target muscles. Combinations with all other treatment options including deep brain stimulation are possible. Recent safety data and availability of immunologically improved BT drugs are now allowing higher BT doses thus expanding the use of BT into more widespread dystonias. PMID- 20590815 TI - Surgical treatment of dystonia. AB - Surgical treatment of dystonia has experienced a tremendous change over the past decade. Whilst selective peripheral denervation is reserved for cervical dystonia refractory to botulinum toxin injections, deep brain stimulation (DBS) of the pallidum has gained a wide scope and presents an elementary column in the treatment of medically refractory patients, nowadays. There is consensus that idiopathic generalized, cervical and segmental dystonia are good indications for DBS, although there is still a paucity of studies providing high-level data according to EBM criteria. Efficacy is maintained on longterm. Several other forms of primary dystonia are still under investigation but it appears that patients with Meige syndrome and myoclonus-dystonia gain also marked benefit. Study of the outcome in secondary dystonia disorders is more complex, in general, but patients with tardive dystonia gain similar improvement than patients with idiopathic dystonia. Overall, the risk profile of pallidal DBS is quite low, and it has been shown to be cognitively safe. The effect of pallidal DBS on non dystonic extremities has not received much attention, albeit there are hints for a pro-akinetic mechanism. Several questions remain to be solved including optimal programming of stimulation settings, battery drain with high stimulation energies and the elucidation of the mechanisms of DBS in dystonia. PMID- 20590816 TI - Deep brain stimulation for dystonia: patient selection and outcomes. AB - In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For some secondary dystonias--like tardive dystonia, myoclonus-dystonia (M-D), NBIA (PANK2), the outcome was very good. Only for the primary generalized dystonias, the efficacy of GPi-DBS has been confirmed in randomised controlled trials. Predictors of outcome are the experience and dedication of the stereotactic team, the selection of patients--the diagnosis and pre-operative screening--and the quality of the post-operative care. Predictors of negative outcome are long duration of the disease--with contractures or scoliosis--and concomitant symptoms like spasticity and cerebellar dysfunction. More studies are required to establish the role of GPi-DBS in the treatment of secondary dystonias. PMID- 20590817 TI - Physiotherapy of focal dystonia: a physiotherapist's personal experience. AB - The approach of the physiotherapist to each form of dystonia is individual and has to be specific. There is not one single method but several strategies related to the different clinical forms. Although there is no standard programme applicable to all forms of cervical dystonia, we can distinguish a number of guidelines for the different clinical forms. In the myoclonic form, emphasis is placed on seeking to immobilize the head, and for the tonic form, on rehabilitating corrector muscles. Physiotherapy and botulinum toxin injections mutually interact in order to reduce the symptoms. Recent studies have shown the clinical benefits of physiotherapy. The physiotherapy of writer's cramp is designed as a re-learning process. The first step is to perform exercises to improve independence and precision of fingers and wrist movements. Then, the muscles involved in the correction of dystonic postures are trained by drawing loops, curves and arabesques. The aim of rehabilitation is not to enable patients with writer's cramp to write as they used to, but to help their dysgraphia evolve towards a fast, fluid and effortless handwriting. A reshaping of the sensory cortical hand representation appears to be associated with clinical improvement in patients with dystonia after rehabilitation. PMID- 20590818 TI - Epidermal growth factor receptor tyrosine kinase inhibitors induce CCL2 and CCL5 via reduction in IL-1R2 in keratinocytes. AB - Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is a transducer of mitogenic signals, and is involved in the pathogenesis and progression of a number of cancers, including non-small cell lung cancer (NSCLC). Gefitinib is an EGFR-TK inhibitor that is clinically used to treat NSCLC; however, this drug frequently causes adverse effects, including skin eruptions. The mechanism underlying these skin reactions is elusive, although it is assumed that they are caused by the inhibition of EGFR-TK signalling in epidermal and adnexal cells. In this article, we demonstrate by immunocytochemistry that the skin lesions of patients treated with oral gefitinib had higher expression of CCL2 and CCL5 compared to normal human epidermis. Further, PD153035, a gefitinib prototype, induced CCL2 and CCL5 mRNA and protein expression in HaCaT and HSC-1 keratinocyte cell lines with or without interleukin-1 (IL-1) treatment in vitro. PD153035 also reduced the levels of interleukin-1 receptor 2 (IL-1R2), an IL-1 decoy receptor. Moreover, we demonstrate that reduction in IL-1R2 by RNA interference increased IL-1-mediated CCL2 and CCL5 mRNA and protein expression. Taken together, our data strongly suggest that IL-1-mediated signalling is activated to induce the high expression of CCL2 and CCL5 via reduction in IL-1R2 in the skin lesions caused by gefitinib. PMID- 20590820 TI - Leishmaniasis, contact hypersensitivity and graft-versus-host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. AB - Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node-resident DC. The skin is the primary interface between the body and the environment and host's various DC subsets, including dermal DC (dDC) and Langerhans cells (LC). Because of their anatomical position in the epidermis, LC are believed to be responsible for induction of adaptive cutaneous immune responses. The functions of LC and dDC in the skin immune system in vivo are manifold, and it is still discussed controversially whether the differentiation of T-cell subtypes (e.g. effector T cells and regulatory T cells) may be initiated by distinct DC subtypes. As skin DC are able to promote or downmodulate immune responses, we chose different skin diseases (cutaneous leishmaniasis, contact hypersensitivity, UV radiation-induced suppression, and graft-versus-host disease) to describe the biological interactions between different DC subtypes and T cells that lead to the development of efficient or unwanted immune responses. A detailed knowledge about the immune modulatory capacity of different cutaneous DC subsets might be helpful to specifically target these cells through the skin during therapeutic interventions. PMID- 20590821 TI - Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata. AB - Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis that function as a local stress response system. Because adrenocorticotropic hormone (ACTH) is an intermediate in the HPA axis from corticotropin-releasing hormone (CRH) signal to cortisol secretion, MC2R that binds only ACTH may be important in the stress response of skin. We investigated the local expression of MC2R by immunohistochemistry to identify the role of ACTH/MC2R in stress associated alopecia areata (AA). MC2R appeared to be highly compartmentalized in scalp skin including the epidermal cells of hair follicles and epidermis, sebaceous and eccrine glands, as well as dermal fibroblasts. The expression of MC2R was lower in AA lesions than in normal scalp tissue in almost all scalp skin cells, especially in epithelial cells. These findings demonstrate that MC2R expression is aberrant in AA and suggest a deficit in ACTH/MC2R activity may play an important role in the pathophysiology of AA. PMID- 20590822 TI - Abstracts of the 35th FEBS Congress. Gothenburg, Sweden. June 26-July 1, 2010. PMID- 20590819 TI - The cycling hair follicle as an ideal systems biology research model. AB - In the postgenomic era, systems biology has rapidly emerged as an exciting field predicted to enhance the molecular understanding of complex biological systems by the use of quantitative experimental and mathematical approaches. Systems biology studies how the components of a biological system (e.g. genes, transcripts, proteins, metabolites) interact to bring about defined biological function or dysfunction. Living systems may be divided into five dimensions of complexity: (i) molecular; (ii) structural; (iii) temporal; (iv) abstraction and emergence; and (v) algorithmic. Understanding the details of these dimensions in living systems is the challenge that systems biology aims to address. Here, we argue that the hair follicle (HF), one of the signature features of mammals, is a perfect and clinically relevant model for systems biology research. The HF represents a stem cell-rich, essentially autonomous mini-organ, whose cyclic transformations follow a hypothetical intrafollicular "hair cycle clock" (HCC). This prototypic neuroectodermal-mesodermal interaction system, at the cross-roads of systems and chronobiology, encompasses various levels of complexity as it is subject to both intrafollicular and extrafollicular inputs (e.g. intracutaneous timing mechanisms with neural and systemic stimuli). Exploring how the cycling HF addresses the five dimensions of living systems, we argue that a systems biology approach to the study of hair growth and cycling, in man and mice, has great translational medicine potential. Namely, the easily accessible human HF invites preclinical and clinical testing of novel hypotheses generated with this approach. PMID- 20590823 TI - Maternal-effect gene Ces5/Ooep/Moep19/Floped is essential for oocyte cytoplasmic lattice formation and embryonic development at the maternal-zygotic stage transition. AB - In a search for genes specifically expressed in mouse embryonic stem cells, we identified one we called Ces5. We found that it corresponded to the Ooep gene, which was recently reported to be expressed specifically in oocytes. Mouse Ces5/Ooep, also called Moep19 or Floped, encoded a 164-amino acid protein, which was detected in the cytoplasm of developing and mature oocytes and in embryos throughout the preimplantation period. To examine its function, we carried out targeted disruption of this gene. The Ces5/Ooep-null mice were grossly normal, but the females were infertile. Although the ovaries and ovulation appeared normal, the embryos from Ces5/Ooep-null females mated with wild-type males showed developmental arrest at the two- or four-cell stage. In addition, their first cleavage was considerably delayed and often asymmetrical. Thus, Ces5/Ooep is a maternal-effect gene. By electron microscopy, we found that the eggs from Ces5/Ooep-null females lacked oocyte cytoplasmic lattices (CPLs), which have long been predicted to function as a storage form for components that are maternally contributed to the early embryo. Further analysis showed that CES5/OOEP was directly associated with the CPLs. These results indicate that CES5/OOEP is an essential component of the CPLs and is required for embryonic development at the maternal-zygotic stage transition. PMID- 20590824 TI - Survival responses to oxidative stress and aging. AB - Oxidative stress is recognized as an important environmental factor in aging; however, because reactive oxygen species (ROS) and related free radicals are normally produced both intra- and extracellularly, air-living organisms cannot avoid the risk of oxidative stress. Consequently, these organisms have evolved various anti-oxidant systems to prevent ROS, scavenge free radicals, repair damaged components and adaptive responses. This review will focus on the repair and adaptive response to oxidative stress, and summarize the changes of these systems as a result aging and their relationship to premature aging. PMID- 20590825 TI - Age-related increase of reactive oxygen generation in the brains of mammals and birds: is reactive oxygen a signaling molecule to determine the aging process and life span? AB - Since Harman proposed the "free-radical theory of aging", oxidative stress has been postulated to be a major causal factor of senescence. The accumulation of oxidative stress-induced oxidatively modified macromolecules, including protein, DNA and lipid, were found in tissues during the aging process; however, it is not necessarily clear which factor is more critical, an increase in endogenous reactive oxygen and/or a decrease in anti-oxidative defense, to the age-related increase in oxidative damage. To clarify the increasing production of reactive oxygen with age, we examined reactive oxygen-dependent chemiluminescent (CL) signals in ex vivo brain slices prepared from different-aged animal brains during hypoxia-reoxygenation treatment using a novel photonic imaging method. The CL signal was intensified during reoxygenation. The signals in SAMP10 (short-life strain) and SAMR1 (control) brain slices increased with aging. The slope of the increase of CL intensity with age in P10 was steeper than in R1. Age-dependent increase of CL intensity was also observed in C57BL/6 mice, Wistar rats and pigeons; however, superoxide dismutase (SOD) activity in the brain did not change with age. These results suggest that reactive oxygen production itself increased with aging. The rate of age-related increases of CL intensity was inversely related to the maximum lifespan of animals. We speculate that reactive oxygen might be a signaling molecule and its levels in tissue might determine the aging process and lifespan. Decelerating age-related increases of reactive oxygen production are expected to be a potent strategy for anti-aging interventions. PMID- 20590826 TI - Age-associated changes of appetite-regulating peptides. AB - Aging is associated with a progressive decrease in appetite and food intake. The reasons for the decline in food intake are multifactorial, and relate to both peripheral and central mechanisms. Current studies about the regulation of food intake suggest that there are many central mediators that control the appetite. To determine the mechanism of age-associated decrease in appetite and food intake, we focused on the age-associated changes of the suppressing and stimulatory effect of some appetite-regulating peptides. At first, we examined cholecystokinin (CCK), one of the typical appetite-suppressing factors. Although sensitivity to CCK is enhanced in old animals, the mechanism underlying this effect has not been elucidated. Next, we focused on the appetite-stimulating peptides, orexin-A, neuropeptide Y (NPY) and ghrelin, which are known to play a critical role in food intake. To determine the age-associated decrease in appetite and food intake, we compared the stimulatory effect of intracerebroventricular administration of orexin-A, NPY and ghrelin. We report the studies of the age-associated changes of appetite-regulating peptides in this review. PMID- 20590827 TI - Association of aldehyde dehydrogenase 2 gene polymorphism with pancreatic cancer but not colon cancer. AB - AIMS: Most of the acetaldehyde, a recognized animal carcinogen, generated during alcohol metabolism is eliminated by liver mitochondrial aldehyde dehydrogenase 2 (ALDH2). More than 40% of Japanese people have the inactive form of ALDH2, and inactive ALDH2 is a risk factor for multiple cancer of the esophagus, as well as head and neck cancer. Possible associations between pancreatic cancer and ALDH2 gene polymorphism, as well as between colon cancer and ALDH2 gene polymorphism, in conjunction with smoking and/or drinking habits, were examined in a Japanese population. METHODS: Patients with pancreatic cancer (n = 187) and with colon cancer (n = 49) were examined. The drinking (5 g ethanol consumption/day) and/or smoking habits as well as ALDH2 gene polymorphism were examined. The age-matched control subjects were recruited in the NILS Longitudinal Study of Aging (LSA). RESULTS: Aging, smoking and inactive ALDH2, but not alcohol, are independent risk factors for pancreatic cancer. The frequency of smoking habits tended to be higher in patients with colon cancer compared with the patients without cancer. However, age, body mass index or the distribution of ALDH2 genotypes did not differ significantly among the patients with colon cancer, colon polyps and others. CONCLUSIONS: Inactive ALDH2 is an independent risk factor for pancreatic cancer, but inactive ALDH2 might not be a risk for colon cancer. PMID- 20590828 TI - Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation. AB - There are significant age-related changes in autonomic nervous system function that are responsible for an impaired ability to adapt to environmental or intrinsic visceral stimuli in the elderly. We review data on changes in autonomic nervous system regulation of cardiovascular and urinary function, as well as data on strategies to improve function. There are data showing alterations in peripheral and central autonomic nerve activity, and decreases in neurotransmitter receptor action that lead to diminished autonomic reactivity (e.g. blood pressure and cerebral blood flow regulation) and poorly coordinated autonomic discharge (e.g. bladder function). Simple strategies for autonomic function improvement and increasing cortical blood flow include walking and somatic afferent stimulation (e.g. stroking skin or acupuncture) to increase sympathetic, parasympathetic and central cholinergic activity. PMID- 20590829 TI - Muscle weakness and neuromuscular junctions in aging and disease. AB - A critical issue in today's super-aging society is the need to reduce the burden of family care while continuing to make our medical institutions supportive. A rapidly emerging, major health concern is the debilitating effect of muscle weakness and atrophy from aging, termed sarcopenia; however, the molecular basis of this condition is not well understood. Our research aim is to elucidate the molecular mechanisms of age-related muscle atrophy and to devise new measures for preventing and treating this disability. A promising treatment for muscle atrophy is the promotion of muscle regeneration by recruiting stem cells into the targeted region. The first requirement is to understand how the motor system, which consists of muscles and motoneurons, is maintained to accomplish that goal. Recent studies in the field of neuroscience have focused on neuromuscular junctions (NMJ), which play important roles in the maintenance of both motor nerves and muscle fibers. Signaling between muscles and motoneurons at NMJ supports interactions within the motor system. To understand the mechanisms involved, we focus our research on the pathogenic processes underlying neuromuscular diseases. The well-known autoimmune disease, myasthenia gravis (MG), serves as a model not only for tracking the pathogenesis and treatment outcomes of all autoimmune diseases, but also for understanding synaptic functions in maintaining the motor system. Here, we describe recent insights into the molecular mechanisms required for the maintenance of NMJ and the related causes of muscle atrophy. PMID- 20590830 TI - Acetylcholine-dopamine balance hypothesis in the striatum: an update. AB - The imbalance between cholinergic activity and dopaminergic activity in the striatum causes a variety of neurological disorders, such as Parkinson's disease. During sensorimotor learning, the arrival of a conditioned stimulus reporting a reward evokes a pause response in the firing of the tonically active cholinergic interneurons in targeted areas of the striatum, whereas the same stimulus triggers an increase in the firing frequency of the dopaminergic neurons in the substantia nigra pars compacta. The pause response of the cholinergic interneurons begins with an initial depolarizing phase followed by a pause in spike firing and ensuing rebound excitation. The timing of the pause phase coincides well with the surge in dopaminergic firing, indicating that a dramatic rise in dopamine (DA) release occurs while nicotinic receptors remain unbound by acetylcholine. The pause response begins with dopamine D5 receptor-dependent synaptic plasticity in the cholinergic neurons and an increased GABAergic IPSP, which is followed by a long pause in firing through D2 and D5 receptor-dependent modulation of ion channels. Inactivation of muscarinic receptors on the projection neurons eventually yields endocannabinoid-mediated, dopamine-dependent long-term depression in the medium spiny projection neurons. Breakdown of acetylcholine-dopamine balance hampers proper functioning of the cortico-basal ganglia-thalamocortical loop circuits. In Parkinson's disease, dopamine depletion blocks autoinhibition of acetylcholine release through muscarinic autoreceptors, leading to excessive acetylcholine release which eventually prunes spines of the indirect-pathway projection neurons of the striatum and thus interrupts information transfer from motor command centers in the cerebral cortex. PMID- 20590832 TI - The turn formation at positions 22 and 23 in the 42-mer amyloid beta peptide: the emerging role in the pathogenesis of Alzheimer's disease. AB - One hallmark of Alzheimer's disease (AD) is the accumulation of amyloid beta (Abeta) peptides in the brain; Abeta mainly consists of 42-mer and 40-mer peptides (Abeta42 and Abeta40). Abeta42 plays a more critical role in the pathogenesis of AD because Abeta42 aggregates much faster and is more toxic than Abeta40. Therefore, there is an urgent need to elucidate the mechanism of aggregation and neurotoxicity of Abeta42 to develop therapeutic agents. Here, we introduce the pathological role of Abeta42 in AD and review our recent findings of the structural analysis of Abeta42 using systematic proline replacement, electron spin resonance and solid-state nuclear magnetic resonance, and the new mechanism of neurotoxicity of Abeta42 through the formation of radicals. PMID- 20590831 TI - Molecular mechanisms of regeneration in Alzheimer's disease brain. AB - Regenerative responses, including re-expression of developmentally regulated proteins, occur in Alzheimer's disease (AD) brain and in beta-amyloid (Abeta) treated neuronal cultures. Brain microenvironment might also be altered by Abeta or by unknown materials in AD brain to make neurons or progenitor cells regenerative. However, these responses and alterations might not be sufficient to replace neuronal loss, but rather might act as an effecter of cell death. For instance, downregulation of growth inhibitory factor/metallothionein-III and upregulation of MAP1B result in both neurite sprouting and neuronal death. The deteriorative regulation of Mash1 and Olig2 by Abeta also leads to differentiation and death of progenitor cells. Clarifying the cell death mechanism accompanied with regenerative responses might be necessary for repairing the nervous system or slowing disease progression in AD. PMID- 20590833 TI - Development of PET radiopharmaceuticals and their clinical applications at the Positron Medical Center. AB - The Positron Medical Center has developed a large number of radiopharmaceuticals and 36 radiopharmaceuticals have been approved for clinical use for studying aging and geriatric diseases, especially brain functions. Positron emission tomography (PET) has been used to provide a highly advanced PET-based diagnosis. The current status of the development of radiopharmaceuticals, and representative clinical and methodological results are reviewed. PMID- 20590834 TI - Changes of telomere length with aging. AB - We reviewed our methodology and results of telomere measurements, with reference to telomere length and aging. Human tissues always showed telomere shortening with age, except for the brain and myocardium. Yearly rates of telomere length reduction in various tissues were mostly within the range 20-60 bp, and thus compatible with that expected from only one round of mitosis. It was suggested that when telomeres were found to be longer in any specific organ in a given individual, then the other organs in that individual would also have longer telomeres. Using the quantitative fluorescence in situ hybridization (Q-FISH) method for telomere measurement, we were able to measure the telomere lengths of various cell types within tissues. Here we summarize the results obtained for various cell types in the stomach, tongue and breast. Our Q-FISH method using our original software program "Tissue Telo" is excellent for measuring telomere lengths using tissue sections and PNA probes. PMID- 20590835 TI - Role of methylation of the hMLH1 gene promoter in the development of gastric and colorectal carcinoma in the elderly. AB - The occurrence of malignant neoplasms increases with advancing age. Although aging and carcinogenesis are basically different processes, they share phenomena such as the accumulation of DNA damage and abnormal proteins. Recent advances in molecular biology have shown an accumulation of genetic and epigenetic changes in both aging and carcinogenesis, as well as the alteration of metabolism, immunosenescence and shortened telomeres. DNA methylation is a representative epigenetic phenomenon and is frequently involved in controlling gene functions during development and tumorigenesis. We herein focused on methylation of genes in the development of gastrointestinal carcinomas in the elderly. The proportion of gastric and colorectal carcinomas with hypermethylation of the hMLH1 promoter increases with age, reaching 25-30% of all carcinomas of the stomach and large intestine in elderly patients. These tumors have clinicopathological and molecular characteristics such as loss of hMLH1 expression, microsatellite instability, poorly differentiated histology, peritumoral inflammatory cell infiltration, low incidence of lymph node metastasis and favorable prognosis. However, methylation-related carcinogenesis accounts for up to approximately one third of tumors, and other mechanisms; for example chromosomal instability as a result of telomere dysfunction, are responsible for the development of most carcinomas in the elderly. PMID- 20590836 TI - Vascular aging: from molecular mechanism to clinical significance. AB - The large and medium-sized arteries in elderly people show varying degrees of intimal and medial change. The medial change is known as age-related medial degeneration and sclerosis (ARMDS). The ARMDS results in systolic hypertension and left ventricular hypertrophy of the heart as a result of loss of arterial elasticity. It also causes aortic dilatation, or even aortic aneurysm. The ARMDS and atherosclerosis are distinct entities, but are often overlapped and confused with each other. The present review mainly focuses on ARMDS and briefly addresses atherosclerosis, and aging of arterioles, capillaries and veins. The smooth muscle cells in the inner half of the aortic media of elderly people degenerate and undergo apoptosis. This causes degradation of elastin fibers and the accumulation of collagen fibers in the media, but the inflammatory infiltrates are scarce. Biochemical studies showed an age-related decrease of elastin and its crosslinks, and an increase of collagen and its crosslink. Because the turnover of elastin is very long, it likely suffers from glycation (Maillard reaction) and glyco-oxidative reaction. The advanced glycation end-products accumulate in the aortic media with increasing age. Alcian-blue positive mucin accumulates in aortic media in elderly people. The major component of the increase of aortic mucin is chondroitin-6-sulfate. Microcalcification is frequent in the inner acellular portion of the aortic media in elderly people. Calcium contents increase with age. In conclusion, the ARMDS is a distinct pathological entity with clinical significance. The pathogenesis of ARMDS is unclear; the mechanical stress of elastin, endothelial dysfunction, and glycation of elastin are proposed. PMID- 20590837 TI - Mitochondrial haplogroups associated with lifestyle-related diseases and longevity in the Japanese population. AB - Recently published results on the association between metabolic syndrome, type 2 diabetes, myocardial infarction or atherothrombotic cerebral infarction and Japanese major haplogroups based on the comprehensive analysis of mitochondrial genome polymorphisms (mtSNP) in the coding region of human mitochondrial DNA (mtDNA), and longevity-related haplogroups are described in the present review. Our aim was to provide information that would allow us to predict the genetic risk for lifestyle-related diseases and thereby contribute to the primary prevention of these conditions. The mitochondrial genome variation is so large that a given haplogroup might consist of various subhaplogroups carrying unique and presumably functional mtSNP. The frequency of each subhaplogroup is sometimes only a few percent. Therefore, large-scale association study is necessary for elucidating the impact of each subhaplogroup on the susceptibility to various common diseases. PMID- 20590838 TI - Habitual physical activity and health in the elderly: the Nakanojo Study. AB - This article provides a detailed overview of both factors influencing habitual physical activity, and relationships between such activity and health in the elderly. Current cross-sectional data from the Nakanojo Study, which we have been carrying out since 2000, indicate substantial associations between the overall health of participants, and both the year-averaged daily step count and the year averaged daily duration of effort undertaken at an intensity >3 metabolic equivalents (MET). In men, the extent of health is associated more closely with the daily duration of activity >3 MET than with the daily step count, whereas in women the association is closer for the step count than for the duration of activity >3 MET. In both sexes, the threshold amount of physical activity associated with better health is greater for physical than for mental benefits: >8000 vs >4000 steps/day and/or >20 vs >5 min/day at >3 MET, respectively. In other words, physical health is better in those spending at least 20 min/day in moderate walking (at a pace of around 1.4 m/s [5 km/h]) and a further >60 min of light activity per day. In contrast, better mental health is associated with much smaller amounts of deliberate physical activity. Both the intensity and the total volume of physical activity are influenced by meteorological factors, particularly precipitation and mean ambient temperature. Activity decreases exponentially to about 4000 steps/day as precipitation increases. Excluding the influence of rainfall, the daily step count peaks at a mean outdoor temperature of around 17 degrees C; above and especially below such readings, physical activity decreases as a quadratic function of temperature. Seasonal changes in the microclimate should thus be considered when designing interventions intended to increase the habitual physical activity of older adults. Based on these findings, we are now developing preventive tactics that should contribute to health promotion, disease prevention and thus a reduction in medical expenses for elderly people. PMID- 20590839 TI - Proteomic approaches to oxidative protein modifications implicated in the mechanism of aging. AB - Accumulation of oxidatively modified proteins is widely observed in aged animal tissues. Protein carbonyls are mostly derived from lysine, arginine, proline and threonine residues under oxidative conditions. Many groups have investigated carbonylated proteins since a convenient immunochemical procedure was established for detecting dinitrophenyl derivatives of carbonyls and applied to proteomic research. An alternative method of tagging with biotin or fluorescent dyes has been also introduced to proteomic analysis of protein carbonyls. Nitrotyrosine was primarily identified as a biomarker of cellular damage and inflammation under nitrosative stress. Nitrated proteins have been subsequently detected in aged animal tissues and Alzheimer's disease affected brains by Western blotting, and identified by mass spectrometry. Protein s-thiolation, a mixed-derivatization of cysteine (Cys) by conjugation of low-molecular-weight thiol compounds, is recognized as protecting functional proteins from more serious damage. A method of biotin labeling has been used in proteomics for tracing protein s-thiolation. Among all kinds of amino acid residues, methionine (Met) is the most susceptible to reactive oxygen species, and Met oxidation seems to occur in ordinary cellular circumstances because most cells contain Met sulfoxide reductases, which might prevent serious cellular damage. In proteomic analysis, Met sulfoxide-containing peptides are generally observed as 16-Da-high mass peaks in peptide mass fingerprinting. A modified procedure of two-dimensional gel electrophoresis, in which proteins are kept under non-oxidative conditions throughout the procedure, is appropriate for the estimation of the Met sulfoxide level of each protein in aged animal tissues and cells to evaluate the pathophysiological significance of Met oxidation in the mechanism of aging. PMID- 20590840 TI - Alteration of brain glycoproteins during aging. AB - Glycosylation is the most common post-translational modification of proteins. Protein sequence data suggested that more than half of all proteins produced in mammalian cells are glycoproteins. Recent studies showed that glycans of secreted glycoproteins affect many protein properties, such as solubility, stability, protease sensitivity and polarity, whereas glycans on cell-surface glycoproteins are involved in various cellular functions, including cell-cell communication. Accordingly, the investigation of glycoprotein changes caused by aging is expected to help understand the aging process and to elucidate age-associated diseases. The present review will summarize our current knowledge of changes found in brain glycoproteins resulting from the aging process. PMID- 20590841 TI - Plasma membrane microdomains in aging and disease. AB - The plasma membrane of eukaryotic cells participates in signal transduction and many other cellular events to maintain the physiological state of cells. In recent decades, much attention has been paid to membrane microdomains, called lipid rafts or membrane rafts, as signaling platforms in the plasma membrane. Lipid rafts are lateral lipid clusters enriched in cholesterol and sphingolipids in which particular molecules are concentrated and participate in membrane mediated signaling events. Recent studies have shown a close relationship between lipid rafts and the age-associated decline and dysregulation of cellular signaling pathways, such as T-cell receptor signaling and cellular senescence related signaling. Lipid rafts have also been implicated in senile diseases and in lifestyle-related diseases whose incidences increase with age. PMID- 20590842 TI - Importance of research on peptidylarginine deiminase and citrullinated proteins in age-related disease. AB - Peptidylarginine deiminases (PAD) are a group of post-translational modification enzymes that citrullinate (deiminate) protein arginine residues in a calcium ion dependent manner. Enzymatic citrullination abolishes positive charges of native protein molecules, inevitably causing significant alterations in their structure and functions. Citrullinated protein has an important physiological purpose; the formation of a cornified layer of skin that covers the human body. Despite this beneficial function, citrullinated protein also has a negative side, because this protein's accumulation in the brain is a possible cause of Alzheimer's disease. In the present review, we introduce PAD and their protein citrullination function, now considered critical for advancing research on aging and disease. PMID- 20590843 TI - Redox regulation, gene expression and longevity. AB - Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod 3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators. PMID- 20590844 TI - Model mice for tissue-specific deletion of the manganese superoxide dismutase gene. AB - Manganese superoxide dismutase (Mn-SOD) is a mitochondrial enzyme that converts toxic O(2)(-) to H(2)O(2). Previous studies have reported that a systemic deficiency in Mn-SOD causes neonatal lethality in mice. Therefore, no mouse model is available for the analysis of the pathological role of O(2)(-) injuries in adult tissues. To explore an adult-type mouse model, we generated tissue-specific Mn-SOD conditional knockout mice using a Cre-loxp system. First, we generated liver-specific Mn-SOD-deficient mice by crossbreeding with albumin-Cre transgenic mice. Mn-SOD proteins were significantly downregulated in the liver of liver specific Mn-SOD knockout mice. Interestingly, the mutant mice showed no obvious morphological abnormalities or biochemical alterations in the liver, suggesting a redundant or less important physiological role for Mn-SOD in the liver than previously thought. Next, we generated heart/muscle-specific Mn-SOD-deficient mice by crossbreeding muscle creatine kinase-Cre transgenic mice. The mutant mice developed progressive dilated cardiomyopathy with specific molecular defects in mitochondrial respiration. Furthermore, brain-specific Mn-SOD-deficient mice that had been developed by crossbreeding with nestin-Cre transgenic mice developed a spongiform encephalopathy-like pathology associated with gliosis and died within 3 weeks of birth. These results imply that the superoxide generated in mitochondria plays a pivotal role in the development and progression of pathologies in the heart and brain, but not in the liver. In conclusion, we successfully generated various tissue-specific Mn-SOD conditional knockout mice that provide useful tools for the analysis of various oxidative stress-associated diseases. PMID- 20590845 TI - Klotho protein deficiency and aging. AB - Aging is inevitable; however, the molecular mechanism of aging has not been fully elucidated. Investigations into aging are facing difficulties because aging is influenced by complex factors such as circumstances, living habits and genetic background. Recently, a variety of animals, such as Caenorhabditis elegans, Drosophila and mice, that have aberrations in their lifespan, have been investigated and a large number of genes related to aging have been found, one of which is alpha-klotho. The alpha-Klotho mouse (alpha-kl(-/-) mouse), which has a defect of the alpha-klotho gene expression, was established a decade ago. It is of great interest because the alpha-kl(-/-) mouse shows various phenotypes resembling human aging. The relationship between aging and alpha-klotho protein function is gradually becoming clear. This review covers the recent advance in alpha-klotho protein research. PMID- 20590846 TI - Pathophysiological significance of senescence marker protein-30. AB - A novel rat liver protein of 30 kDa, SMP30 decreases with aging. This protein is expressed most prominently in the liver and kidneys among the various organs. Its gene is located on the X chromosome. No functional domain was recognized in the entire amino acid sequence. Recently, we found a homology between rat SMP30 and two species of bacterial gluconolactonase (EC 3.1.1.17). The lactonase reaction with L-gulono-gamma-lactone is the penultimate step in vitamin C (L-ascorbic acid) biosynthesis. SMP30-knockout (KO) mice fed a vitamin C-deficient diet displayed symptoms of scurvy. In SMP30-KO mice, hepatocytes were more susceptible to apoptosis induced by TNF-alpha plus actinomycin D than hepatocytes from wild type mice. Two morphological features considered to be a hallmark of senescence are apparent in SMP30-KO mice. At 12 months of age, SMP30-knockout mice had clearly visible deposits of lipofuscin and senescence-associated beta galactosidase (SA-beta-GAL) in their renal tubular epithelia. These features are compatible with high electron dense deposits in lysosomes. This observation suggests that the SMP30-knockout mouse is a useful model of ordinal senescence. PMID- 20590847 TI - Acetyl-L-carnitine improves aged brain function. AB - The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats. PMID- 20590848 TI - Recent advances in gerontology reveal that some of those old stories are the basis for today's scientific facts. Preface. PMID- 20590849 TI - Building our global family--achieving treatment for all. AB - SUMMARY: Building our global family by reaching out to women, children and youth and those in sub-Saharan Africa to achieve Treatment for All. The World Federation of Hemophilia (WFH) has committed to recognizing and incorporating the critical and important challenges that are faced by women with bleeding disorders within our global family. The next crucial steps include the development of outreach and registry programmes which can be adapted globally to accelerate the identification of such women, and to educate and guide them to the appropriate clinical care setting. Equally important, awareness must be raised within the broader medical community where women would typically first present with clinical symptoms. Family practitioners, nurse-midwives, obstetricians, gynaecologists and community health clinics will increasingly be strategic and central to WFH outreach efforts, in addition to serving as new care partners essential to the multidisciplinary model of care. Adapting and implementing the WFH development model regionally within Africa is proving to be a successful approach both for the introduction as well as the development of sustainable national care programmes for patients with bleeding disorders. The targeted development of solid national programmes such as in South Africa, Senegal and Kenya has expanded the training capacity of the WFH, as well as providing key regional examples. Local medical professionals are now responsible for providing the training in many regional programmes. Children with bleeding disorders in low-income countries are at great risk of dying young. WFH data demonstrate that among such patients, as the economic capacity of a country decreases so does the ratio of adults to children. The organization of care, training of a multi-disciplinary healthcare team, and education of patients and their families lead to improved mortality independent of economic capacity or increased clotting factor concentrate availability. Additionally, through enhanced youth education, awareness and engagement, we will assure continuity within WFH national member organizations, build greater unity within our global family and capture the innovation and creativity of their ideas to improve Treatment for All. PMID- 20590850 TI - The challenge of an ageing haemophilic population. AB - SUMMARY: Life expectancy for haemophilia has increased significantly in many countries. This represents a major success of the improved safety of therapeutic materials to treat haemophilia and of improved quality of care. This improved longevity will generate a population of older individuals with haemophilia with complex medical problems associated with age and managing such clinical issues is likely to be challenging. PMID- 20590851 TI - Biovigilance and pharmacovigilance for haemophilia. PMID- 20590852 TI - Special lectures in haemophilia management. AB - SUMMARY: During the last two decades major advances have been achieved in the management of haemophilia. Modern approaches aimed at preventing the recurrent bleedings and their sequelae have been widely adopted. Major challenges of intensive treatment regimens employed today, such a short half life of haemophilia therapeutics with a need for frequent injections and the risk of inhibitor, encourage further development towards the production of factor concentrates with prolonged efficacy and reduced immunogenicity. Intensive research work on gene therapy aimed at ultimate cure of haemophilia by the restoration of missing factor FVIII (FVIII) and factor IX (FIX) production is ongoing. The current issues of gene therapy and mechanisms, modifying the host immune response to the FVIII and FIX transgene material and the coagulation factors expressed are the topic of the Arosenius lecture by Katherine High. Despite an extensive research on mechanisms leading to inhibitor development, the real reason of these serious complications of haemophilia therapy still remains unclear. Alessandro Gringeri will discuss the immunogenicity of plasma derived FVIII (pd FVIII) and recombinant FVIII (rFVIII) concentrates as one of potential, treatment related, and probably 'modifiable' risk factors for inhibitor development. The SIPPET study--a new prospective, randomised study aimed to reveal real incidence of inhibitors in patients treated with either pdFVIII or rFVIII will be presented. PMID- 20590854 TI - The application of genetics to inherited bleeding disorders. AB - SUMMARY: Most bleeding disorders encountered in clinical practice will be diagnosed, at least initially, by phenotypic assays. However, since the characterization of the genes that encode coagulation factors in the 1980s, significant progress has been made in translating this knowledge for diagnostic and therapeutic purposes. For the haemophilias, in particular, molecular genetic testing to determine carrier status, prenatal diagnosis and prediction of the likelihood of inhibitor development has now become an established component of comprehensive clinical management. For von Willebrand's disease (VWD), significant recent advances have allowed for the establishment of genotype phenotype correlations that have improved our understanding of the disease. The availability of high density single nucleotide polymorphism (SNP) maps will allow investigators to probe the genetic basis of the general symptoms of bleeding and bruising using a comprehensive genome-wide approach. This article will review the state-of-the-art for molecular diagnostics for both haemophilia and VWD and will end with a discussion of plans for an international genome-wide association study (GWAS) designed to improve our understanding of blood coagulation. PMID- 20590853 TI - Unique strategies for therapeutic gene transfer in haemophilia A and haemophilia BWFH State-of-the-Art Session on Therapeutic Gene Transfer Buenos Aires, Argentina. AB - SUMMARY: Gene therapy of haemophilia has been initiated through a number of approaches including expression in muscle, liver and omental implanted fibroblasts, or i.v. injection of an expression construct under the control of a ubiquitous promoter. In all these approaches, the goal was to have factor VIII (FVIII) or factor IX (FIX) synthesized so that it restored the levels of the missing protein in blood. The three talks in this session are totally, or at least in part, directed at strategies that may be clinically effective even in the absence of correction of the missing plasma clotting factor, although the haematopoietic stem cell or blood outgrowth endothelial cell therapy could achieve plasma correction as well. Two of the approaches achieve localized coagulation factor expression without necessarily correcting the systemic defect- one is with synthesis of FVIII or FIX within the joint space and the other is with the local release of FVIII (or FIX) by platelets at the site of vascular injury. All of the three approaches have demonstrated efficacy in small animal models and are now the subject of larger animal studies. None has yet to progress to human trials. PMID- 20590855 TI - Viral pathogens. AB - SUMMARY: Despite continuous improvement in safety and purity of blood products for individuals with haemophilia, transmissible agents continue to affect individuals with haemophilia. This chapter addresses three viral pathogens with significant clinical impact: HIV, hepatitis C and parvovirus B19. Hepatitis C is the leading cause of chronic hepatitis and the major co-morbid complication of haemophilia treatment. Clinically, asymptomatic intermittent alanine aminotransferase elevation is typical, with biopsy evidence of advanced fibrosis currently in 25%. Current treatment is effective in up to 70%, and many new agents are in development. For those progressing to end-stage liver disease, liver transplantation outcomes are similar to those in non-haemophilia subjects, although pretransplant mortality is higher. HIV infection, the second leading co morbid condition in haemophilia, is managed as a chronic infection with highly active antiretroviral therapy (HAART). HAART also slows hepatitis C virus (HCV) progression in those with HIV/HCV co-infection. Viral inactivation and recombinant technologies have effectively prevented transfusion-transmitted viral pathogens in haemophilia. Human parvovirus B19 infection, typically associated with anaemia or, rarely severe aplastic crisis, is a non-lipid enveloped virus, for which standard inactivation techniques are ineffective. Thus, nucleic acid testing (NAT) to screen the blood supply for B19 DNA is currently under consideration by the Food and Drug Administration. To the extent, viral inactivation, recombinant, and NAT technologies are available worldwide, and the lifespan for those with haemophilia is approaching that of the normal population. The purpose of this chapter is to provide an update on three clinically significant transfusion-transmitted viral pathogens. PMID- 20590856 TI - Animal models of inhibitors. AB - SUMMARY: Antibody responses to clotting factor concentrates remain a major treatment limitation. In conjucation with ongoing clinical studies, the pathogenesis and potential treatment of clotting factor immune responses is being evaluated in a variety of animal models. PMID- 20590857 TI - Clinical issues in inhibitors. AB - SUMMARY: Anamestic inhibitors represent the major complication of haemophilia therapy now that clotting factor concentrates are virtually free of pathogen transmission risk. Conventional clotting factor replacement is usually insufficient to prevent or treat bleeding in a haemophilia patient with a high responding inhibitor so that alternative treatment with bypassing agents is required. Despite their relative efficacy, their use does not achieve the same invariable haemostasis that patients without inhibitors do following treatment with factor concentrate replacement. This has led to the attempt to eradicate such inhibitors with immune tolerance induction. Success is not invariable, however, and many patients with long-term persistent high-titre inhibitors continue to experience great morbidity. Recently, this has given rise on a limited basis to attempts to use bypassing agents in prophylaxis regimens in an effort to alleviate this extreme morbidity. Each of these strategies is discussed in the context of their relative benefits and risks. PMID- 20590858 TI - New developments in laboratory diagnosis and monitoring. PMID- 20590860 TI - Considerations in the laboratory assessment of haemostasis. AB - SUMMARY: This review outlines a number of key issues when performing laboratory testing of homeostasis. The effect pre-analytical variables have on the reliability and consistency of screening tests is often forgotten due to a lack of understanding and awareness. This can be improved through educating healthcare professionals who are involved in taking blood for assessment. Recent advances in coagulation testing have not enabled laboratories to replace the Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) screening tests with more advanced assays and they continue to play an important role with the advantage of being easily automated. However, there are many analysers on the market, each with varying sensitivity to coagulation defects and it is important to keep this in mind when interpreting results. PMID- 20590859 TI - von Willebrand's disease diagnosis and laboratory issues. AB - SUMMARY: In this paper, the recent developments in the diagnosis and laboratory issues of von Willebrand's disease (VWD) are presented. Dr. Castaman reviews the functional tests available for the diagnosis of VWD and their pathophysiological significance, focusing on which tests are best used in the diagnosis and classification of VWD. Dr Montgomery reviews an emerging issue that is accelerated clearance of von Willebrand factor (VWF) occurring in some variants of VWD. This phenotype can be suspected by the presence of an increased ratio between the VWF propeptide and the VWF antigen. These patients have typically a robust, but short-lived increase of FVIII and VWF after desmopressin. Dr Meschengieser reviews the determinants of bleeding after surgery in patients with VWD, emphasizing the role of bleeding history in predicting this risk. PMID- 20590861 TI - Haemophilia A and von Willebrand's disease. AB - SUMMARY: Deficient or defective coagulation factor VIII (FVIII) and von Willebrand factor (VWF) can cause bleeding through congenital deficiency or acquired inhibitory antibodies. Recent studies on type 1 von Willebrand's disease (VWD), the most common form of the disease, have begun to explain its pathogenesis. Missense mutations of varying penetrance throughout VWF are the predominant mutation type. Other mutation types also contribute while about one third of patients have no mutation identified. Enhanced clearance and intracellular retention contribute to pathogenic mechanisms. Chromogenic substrate (CS) methods to determine FVIII coagulant activity have several advantages over one-stage methods, which include minimal influence by variable levels of plasma components, notably lupus anticoagulant. Direct proportionality between FVIII activity and FXa generation results in high resolution at all FVIII levels, rendering the CS method suitable for measuring both high and low levels of FVIII activity. FVIII inhibitors in patients with inherited or acquired haemophilia A present several challenges in their detection and accurate quantification. The Nijmegen method, a modification of the Bethesda assay is recommended for inhibitor analysis by the International Society on Thrombosis and Haemostasis. Understanding potential confounding factors including heparin and residual FVIII in test plasma, plus optimal standardization can reduce assay coefficient of variation to 10-20%.These areas are all explored within this article. PMID- 20590862 TI - Tests of global haemostasis and their applications in bleeding disorders. AB - SUMMARY: There is a potential for significant paradigm shift in the assessment of haemostasis from the conventional plasma recalcification times, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), which correspond to artificially created compartments of haemostasis to tests that assess the entire process in a more physiological and holistic manner. These include the thrombin generation test, thromboelastogram and the clot wave form analysis. While these tests have been described many years ago, there is renewed interest in their use with modified technology for assessing normal haemostasis and its disorders. Although early data suggest that they can provide much greater information regarding the overall haemostasis process and its disorders, many challenges remain. Some of them are possible only on instruments that are proprietary technology, expensive and are not widely available. Furthermore, these tests need to be standardized with regard to their reagents, methodology and interpretation, and finally, much more data need to be collected regarding clinical correlations with the parameters measured. PMID- 20590863 TI - Quality issues in laboratory haemostasis. PMID- 20590864 TI - Mild haemophilia: a disease with many faces and many unexpected pitfalls. AB - SUMMARY: Despite major advances in diagnosis and treatment, the management of patients with mild haemophilia (MH) remains a major challenge. Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU mL(-1). The bleeding associated with mild haemophilia is most frequently episodic, occurring during surgery or following trauma. Spontaneous bleeding is rare. Diagnosis is sometimes delayed because of insensitivity of screening clotting assays or discrepancies in factor VIII activity as measured by different assays. The treatment of choice in mild haemophilia A is desmopressin, which typically induces a 2-6-fold increase of factor VIII over baseline. However, desmopressin has its limitations in this setting such as the occurrence of tachyphylaxis and failure to respond in an undetermined proportion of patients. Factors underlying poor biological response or magnitude of response to desmopressin are incompletely understood. Inhibitor development in mild haemophilia is particularly distressing. This complication arises at an older age in this patient group because of infrequent need for factor VIII replacement. Inhibitors in mild haemophilia patients often cross react with endogenous factor VIII resulting in severe spontaneous bleeding frequently in a postoperative setting. Intensive perioperative use of factor VIII and some specific mutations induce a particularly high risk for inhibitor development, but risk factors are incompletely understood. For reasons of the older age of the patients, treatment of bleeding with bypassing agents may cause major thrombotic complications. Data on therapeutic options for inhibitor eradication in patients with mild haemophilia are particularly scarce. With increased life-expectancy for all haemophilia patients, the group of elderly patients with mild haemophilia requiring major surgery will further increase. Prevention of inhibitors, particularly in this patient group, should be a major topic of interest in both clinic and research. PMID- 20590865 TI - State-of-the-art imaging techniques for the evaluation of haemophilic arthropathy: present and future. AB - SUMMARY: In spite of the fact that the diagnosis of haemophilia is essentially clinical and laboratory-based, imaging has become an important tool for the evaluation of complications, diagnostic confirmation and/or complementation and therapeutic follow-up in haemophilic arthropathy. Radiography remains the workforce horse in the diagnosis and follow-up of haemophilic arthropathy. The radiographical findings in arthropathy follow an expected sequence of events and are overall similar in different joints. Magnetic resonance imaging (MRI) has advantages over radiography based on its capability of visualizing soft tissue and cartilage changes in haemophilic joints. The recent development and standardization of MRI scoring systems for measuring soft tissue and cartilage abnormalities may enable the comparison of pathological joint findings in clinical trials conducted at different institutions across the world. The implementation of high-frequency transducers and colour/power Doppler capabilities has provided new insights for clinical applications of ultrasonography (US) in haemophilic arthropathy. In spite of the imaging modality's technical challenges such as operator-dependency, US has advantages over MRI. One of these advantages is its ability of differentiating synovium hypertrophy and hemosiderin deposition, which is not possible with MRI given the presence of susceptibility artefacts from extracellular hemosiderin on gradient echo MR images. In addition to the aforementioned conventional imaging modalities, novel imaging techniques (blood oxygen level dependent, ultrasmall superparamagnetic iron-oxide contrast-enhanced, and T1 and T2 mapping MRI, ultrasound biomicroscopy, microbubble contrast-enhanced US and positron emission tomography, among others) hold promise for early assessment of haemophilic arthropathy in the future upon completion of their clinical validation. PMID- 20590866 TI - Management of arthrofibrosis in haemophilic arthropathy. AB - SUMMARY: Hemophilic arthropathy is one of the conditions most associated with arthrofibrosis and loss of range of motion. Progressive fibrosis of synovium leads to pain, spasm, and shortening of muscles, resulting in joint contractures and restriction of joint motion. It is common to see even young children with severe loss of motion of elbows, knees and ankles. Treatment should be primarily by physiotherapy, splintage, and corrective devices. The late or severe cases may require surgical correction in the form of soft-tissue procedures, osteotomy and especially joint replacement. PMID- 20590867 TI - Update on pathogenesis of the bleeding joint: an interplay between inflammatory and degenerative pathways. PMID- 20590868 TI - Haemophilic arthropathy. PMID- 20590869 TI - Update from MSK committee. PMID- 20590870 TI - The ankle joint. PMID- 20590871 TI - Electrotherapy: yesterday, today and tomorrow. AB - The use of electrotherapy has been part of physical therapy treatment for the past few decades. There have been numerous modalities used such as TENS, interferential, diathermy, magnetic therapy, ultrasound, laser and surface electromyography to name a few. There has been an upsurge in the past decade of new and innovative modalities. There needs to be extensive research on each of these electrotherapy devices to determine the proper use of each device. PMID- 20590872 TI - Controversial subjects in musculoskeletal care of haemophilia: cross fire. PMID- 20590873 TI - Comprehensive elements of a physiotherapy exercise programme in haemophilia--a global perspective. AB - SUMMARY: Exercise programmes for people with haemophilia are usually designed and implemented to help manage the recovery after a haemarthrosis or a muscle bleed, or as a tool to help prevent bleeding episodes from occurring. In this article, we have identified individual components of exercise that are often applied as separate entities, but may also need to be implemented in concert for optimized impact. Although it may be necessary on occasion to bias an exercise programme towards one component over the others, it is important to recognize that the various elements of exercise are not mutually exclusive. Decreased flexibility, strength and proprioception, will result in an impairment of balance and a loss of function. Programme design should whenever possible be guided by proven methodology in terms of how each component is incorporated, and more specifically how long to perform the exercise for and how many repetitions should be performed. We recognize, however, that this is not always possible and that there is significant value in drawing from the experience of clinicians with specialized training in the management of haemophilia. In this study, both perspectives are presented, providing reference-based reviews of the mechanics of the various elements of exercise as well as the expert opinions of the authors. Research that has been completed using patients with conditions other than haemophilia may or may not have a direct application with the bleeding disorders population, but the programme design based on principles of tissue healing in addition to disease specific knowledge should be encouraged. PMID- 20590874 TI - Vascular haemostasis. AB - SUMMARY: While the majority of this session will deal with selected inherited vascular abnormalities that may manifest as a haemorrhagic disorder, the initial discussion by Dr Key will focus on the interplay between the vessel wall and components of the coagulation system, with a focus on haemophilia A and B. Although it is generally accepted that physiological haemostasis is triggered by contact of blood with tissue factor (TF), there remains some controversy regarding the cellular origin of TF in vivo. In addition, the initiation and propagation of thrombin generation are highly dependent on the balance of pro- and anticoagulant functions of endothelium, a profile that varies significantly throughout the vasculature. Drs De Paepe and Malfait address heritable collagen disorders such as the Ehlers-Danlos syndromes (EDS), a heterogeneous group of diseases involving the skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding fibrillar collagens, or in genes coding for enzymes involved in posttranslational modifications of collagens. Accurate biochemical and molecular testing is now available for most EDS subtypes and can direct genetic counselling and medical management for these disorders. Dr Shovlin reviews recent developments in hereditary haemorrhagic telengiectasia (HHT), a frequently undiagnosed disorder characterized by arteriovenous malformations in multiple organs. These abnormal blood vessels are the result of mutations in one of a number of genes whose protein products influence TGF-beta signalling in vascular endothelial cells. Several HHT management guidelines have been published and are discussed. PMID- 20590875 TI - Inherited disorders of platelet function and challenges to diagnosis of mucocutaneous bleeding. AB - SUMMARY: Platelets play a pivotal role in the arrest of bleeding at sites of vascular injury. Following endothelial damage, they respond rapidly by adhesion to subendothelial matrix proteins resulting in platelet activation, spreading, aggregation, secretion and recruitment of additional platelets to form the primary haemostatic plug. This mass provides a surface for thrombin generation and fibrin mesh formation that stabilizes the clot. Careful study of patients with inherited platelet disorders and, subsequently, of informative animal models, has identified structural platelet abnormalities that have enhanced our understanding of platelet function. The investigations of rare, but severe, inherited platelet disorders have led us to the discovery of causative molecular defects. One of the most informative is the rare autosomal recessive disorder Glanzmann thrombasthenia, caused by defect or deficiency in the platelet integrin alphaIIbbeta3, resulting in absent platelet aggregation and a significant clinical bleeding diathesis. Our new challenge is to understand the mechanisms underlying more common, but less well-defined, mucocutaneous bleeding (MCB) disorders. Present diagnostic testing for platelet function disorders and von Willebrand's Disease often fails to identify the cause of bleeding in individuals with inherited MCB. PMID- 20590876 TI - Women and bleeding disorders. AB - SUMMARY: While women are rarely affected by haemophilia, they are equally as likely as men to have other bleeding disorders. Menorrhagia, or heavy menstrual bleeding, is the most common symptom that they experience. Not only is menorrhagia more prevalent among women with bleeding disorders, but bleeding disorders are more prevalent among women with menorrhagia. Although menorrhagia is the most common reproductive tract manifestation of a bleeding disorder, it is not the only manifestation. Women with bleeding disorders appear to be at an increased risk of developing haemorrhagic ovarian cysts and possibly endometriosis. Women suspected of having a bleeding disorder or being a carrier of haemophilia should be offered diagnostic testing before getting pregnant to allow for appropriate preconception counselling and pregnancy management. During pregnancy, women with bleeding disorders may be at an increased risk of bleeding complications. At the time of childbirth, women with bleeding disorders appear to be more likely to experience postpartum haemorrhage, particularly delayed or secondary postpartum haemorrhage. As women with bleeding disorders grow older, they may be more likely to manifest gynaecological conditions which present with bleeding. Women with bleeding disorders are more likely to undergo a hysterectomy and are more likely to have the operation at a younger age. While women with bleeding disorders are at risk for the same obstetrical and gynaecological problems that affect all women, women with bleeding disorders are disproportionately affected by conditions that manifest with bleeding. Optimal management involves the combined expertise of haemostasis experts and obstetrician-gynaecologists. PMID- 20590877 TI - Bleeding disorders in neonates. AB - SUMMARY: Bleeding disorders may present during the neonatal period, however, absent patient history along with unique physical signs, physiologically decreased levels of plasma proteins and laboratory variations of platelet function tests may render any diagnosis difficult to establish. Intra cranial haemorrhage (ICH) may be the clinical presenting symptom of a severe coagulation factor deficiency. Haemophilia in the newborn period poses unique challenges in diagnosis and management, Data presented from the UDC and similar surveillance systems world-wide can be used to further clinical research and improve management strategies. Development haemostasis should be considered as well as laboratory variations of coagulation tests while evaluating and diagnosis neonates suspected of bleeding disorders. Therapy of bleeding episodes in the neonate relies upon proper replacement and repeated haemostatic evaluation of patients' status, while dealing with underlying etiological causes. This manuscript discusses the unique aspects of clinical presentation, laboratory assessment, and treatment of various bleeding disorders in neonates. PMID- 20590878 TI - Variant Creutzfeldt-Jakob disease. AB - SUMMARY: Variant Creutzfeldt-Jakob disease (CJD) is an emerging form of human prion disease caused by oral exposure to the bovine spongiform encephalopathy agent. Most cases have occurred in the UK, but smaller numbers of cases have been identified in 10 other countries worldwide. All confirmed cases belong to a single genetic subgroup defined by methionine homozygosity at codon 129 in the prion protein gene. Variant CJD has a widespread distribution of infectivity in the body, involving lymphoid tissues during at least the latter part of the incubation period. This is unlike other forms of human prion disease, and raised concerns that the transmissible agent might also be present in blood. To date, four probable cases of variant CJD infection have been identified following transfusion of packed red blood cells from asymptomatic donors who subsequently died from variant CJD. Recently, one case of likely transmission of variant CJD infection by UK factor VIII (FVIII) concentrates has been reported in an elderly haemophilic patient in the UK, who had been treated with FVIII produced from pooled plasma to which a donor who subsequently died from variant CJD had contributed. The recipient showed no signs or symptoms of variant CJD during life, but evidence of variant CJD infection was detected in his spleen following a postmortem examination. Continued surveillance is required to investigate the prevalence of secondary variant CJD infection in other patients with bleeding disorders who have been treated with UK-sourced pooled plasma products. PMID- 20590879 TI - Prophylaxis in the haemophilia population. AB - SUMMARY: Prophylaxis is recommended as preventive therapy for young boys with severe haemophilia in countries where safe factor concentrates are available. This recommendation is supported by results from a randomized, controlled study that compared on-demand therapy with full-dose prophylaxis (Manco-Johnson MJ, Abshire TC, Shapiro AD et al. N Engl J Med 2007;357:535). It is important to distinguish primary vs. secondary prophylaxis. Primary prophylaxis refers to preventive treatment started before the onset of joint damage, whereas secondary prophylaxis refers to treatment started after joint damage has occurred. Whereas the benefits of primary prophylaxis are well documented, data relating to secondary prophylaxis are limited, especially in the adolescent/adult haemophilia population. Failure of prophylaxis may relate to several variables, including: (i) underlying status of the joints; (ii) poor compliance; (iii) participation in high-risk activities and (iv) unfavourable pharmacokinetics (PK), i.e., too rapid elimination of infused coagulation factors. There is evidence that the risk of joint bleeding in individuals with severe haemophilia A relates to time spent with factor levels < 1% (Collins PW, Blanchette VS, Fischer K et al. J Thromb Haemost 2009;7:413); this variable is strongly influenced by frequency of factor infusions and the individual's PK profile. Key ongoing questions relating to prophylaxis include: (1) what is the optimal regimen for initiating primary prophylaxis; (2) role of prophylaxis in the adolescent/young adult haemophilia population and (3) role of prophylaxis in individuals with severe von Willebrand's disease and other rare inherited coagulation disorders. The role of novel long-acting factor concentrates for prophylaxis will also need to be evaluated. PMID- 20590880 TI - The role of prophylaxis in bleeding disorders. AB - SUMMARY: The rationale for long-term prophylaxis in more severe forms of von Willebrand's disease (VWD) is obvious, as mucosal bleeding and haemophilia-like joint bleeds resulting in chronic morbidity may occur. However, the experience with prophylactic treatment in this group is scanty. An international VWD Prophylaxis Network (VWD PN) was established in 2006. The VWD PN will investigate prophylaxis with retrospective and prospective studies. Eighteen centres in Europe and North America are recruiting patients and an additional 40 centres are preparing for or evaluating participation. In the absence of randomized prospective studies for most rare bleeding disorders, guidelines for prophylaxis are a subject of controversy. In situations where there is a strong family history of bleeding, long-term prophylaxis is administered in selected cases. Short intervals of prophylaxis can also be given before some surgeries or during pregnancy. The benefits of prophylaxis must be balanced by the risk of side effects. Therefore, it is essential to delineate its management in a specialized comprehensive care environment. In haemophilia, decades of clinical experience and numerous retrospective and, recently, prospective studies clearly demonstrate that prophylactic treatment is superior to on-demand treatment, regardless of whether the outcome is the number of joint- or life-threatening bleeds, arthropathy evaluated by X-ray or MRI, or quality of life measured by generic or haemophilia-specific instruments. Optimal prophylactic treatment should be started early in life (primary prophylaxis) but various options exist for the dose and dose interval. These depend on the objective of treatment in the individual patient, which, in turn, is dependent on resources in the health care system. PMID- 20590881 TI - Factor VIII and von Willebrand factor--too sweet for their own good. AB - SUMMARY: Although factor VIII (FVIII) and von Willebrand factor (VWF) are products of two distinct genes, they circulate in plasma as a tight non-covalent complex. Moreover, they both play a critical role in the haemostatic process, a fact that is illustrated by the severe bleeding tendency associated with the functional absence of either protein. FVIII is an essential cofactor for coagulation factor IX, while VWF is pertinent to the recruitment of platelets to the injured vessel wall under conditions of rapid flow. FVIII and VWF have in common that they are heavily glycosylated: full-length FVIII contains 20 N-linked and at least seven O-linked glycans, while VWF contains 12 N-linked and 10 O linked glycans. Three decades of research have revealed that the carbohydrate structures of FVIII and VWF contribute to many of the steps that can be distinguished in the life-cycle of these proteins, including biosynthesis/secretion, function and clearance. In this review, several of these aspects will be discussed. In addition, the interaction of the FVIII/VWF complex with two families of carbohydrate-binding proteins, i.e. Galectins and Siglecs, and their potential physiological relevance will be discussed. PMID- 20590882 TI - Meta-analysis of randomized controlled trials on the effectiveness of somatostatin analogues for pancreatic surgery: a Cochrane review. AB - BACKGROUND: The use of synthetic analogues of somatostatin following pancreatic surgery is controversial. The aim of this meta-analysis is to determine whether prophylactic somatostatin analogues (SAs) should be used routinely in pancreatic surgery. METHODS: Randomized controlled trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Data were extracted from these trials by two independent reviewers. The risk ratio (RR), mean difference (MD) and standardized mean difference (SMD) were calculated with 95% confidence intervals (95% CIs) based on intention-to-treat or available case analysis. RESULTS: Seventeen trials involving 2143 patients were identified. The overall number of patients with postoperative complications was lower in the SA group (RR 0.71, 95% CI 0.62 0.82), but there was no difference between the groups in perioperative mortality (RR 1.04, 95% CI 0.68-1.59), re-operation rate (RR 1.15, 95% CI 0.56-2.36) or hospital stay (MD -1.04 days, 95% CI -2.54 to 0.46). The incidence of pancreatic fistula was lower in the SA group (RR 0.64, 95% CI 0.53-0.78). The proportion of these fistulas that were clinically significant is not clear. Analysis of results of trials that clearly distinguished clinically significant fistulas revealed no difference between the two groups (RR 0.69, 95% CI 0.34-1.41). Subgroup analysis revealed a shorter hospital stay in the SA group than among controls for patients with malignant aetiology (MD -7.57 days, 95% CI -11.29 to -3.84). CONCLUSIONS: Somatostatin analogues reduce perioperative complications but do not reduce perioperative mortality. However, they do shorten hospital stay in patients undergoing pancreatic surgery for malignancy. Further adequately powered trials of low risk of bias are necessary. PMID- 20590883 TI - Intraoperative portal vein blood flow predicts allograft and patient survival following liver transplantation. AB - BACKGROUND: We hypothesized that operative variables might predict survival following liver transplantation. METHODS: We examined perioperative variables from 469 liver transplants carried out at the University of Washington during 2003-2006. Logistic regression determined the variables' contributions to survival at 30, 90 and 365 days. RESULTS: Portal vein blood flow (>1 l/min) was significant to patient survival at 30, 90 and 365 days. Complete reperfusion was only a significant predictor of survival at 30 days. This provided model receiver operating characteristic (ROC) area under the curve (AUC) statistics of 0.93 and 0.87 for 30 and 90 days, respectively. At 365 days, hepatic artery blood flow (>250 ml/min) combined with portal vein blood flow was significantly predictive of survival, with an AUC of 0.74. A subset analysis of 110 transplants demonstrated improved 1-year survival with more aggressive vascular revisions. DISCUSSION: Portal vein blood flow is a significant predictor of survival after liver transplantation. Initially, the liver's survival is based on portal vein blood flow; however, subsequent biliary problems and patient demise result from both poor portal vein and inadequate hepatic artery blood flow. PMID- 20590884 TI - Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study. AB - BACKGROUND: Transarterial chemoembolization (TACE) with drug-eluting beads (DEB) is a new treatment modality. Little is known about prognostic factors affecting survival after DEB TACE for patients with hepatocellular carcinoma (HCC). METHODS: Patients who underwent TACE with doxorubicin DEB for unresectable HCC during 2006-2008 were studied. Survival was calculated from the day of first transcatheter therapy. Survival analysis was performed using Kaplan-Meier estimations. Survival curves were compared using the log-rank test. RESULTS: Fifty patients underwent chemoembolization with doxorubicin DEB. They included 39 women and 11 men, with a median age of 57.5 years (range 28-91 years). Eighteen patients died during the study period and 32 remained alive. Overall survival rates at 6 months, 1 year and 2 years from the first administration of doxorubicin DEB TACE were 71%, 65% and 51%, respectively. Prognostic factors found to be significant on univariate analysis were Child-Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3.0 g/dl, Model for End-stage Liver Disease (MELD) score, serum alphafetoprotein (AFP), Cancer of the Liver Italian Programme (CLIP) score, tumour satisfying Milan criteria, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and Barcelona Clinic Liver Cancer (BCLC) staging. CONCLUSIONS: Child-Pugh class, Okuda staging, bilirubin > 2 mg/dl, albumin < 3 g/dl, MELD score, serum AFP, CLIP score, Milan criteria, ECOG PS and BCLC staging were found to be prognostic markers of survival after treatment with doxorubicin DEB TACE in patients with unresectable HCC. PMID- 20590885 TI - Contrast-enhanced intraoperative ultrasound improves detection of liver metastases during surgery for primary colorectal cancer. AB - BACKGROUND: Computed tomography (CT) is the most common staging investigation in colorectal cancer (CRC). Up to 25% of patients are found to have previously undetected hepatic lesions when intraoperative ultrasound (IOUS) of the liver is used during CRC resection. We aimed to assess the ability of IOUS to detect additional liver lesions/metastases at primary colorectal resection, and to evaluate whether contrast-enhanced IOUS (CE-IOUS) improves the detection and characterization of hepatic lesions. METHODS: We performed a single-centre, prospective pilot study. At CRC resection, patients underwent IOUS of the liver. Contrast-enhanced IOUS of the liver was undertaken using i.v. sulphur hexafluoride micro-bubbles (SonoVue, 4.8 ml). Findings of CT, non-enhanced IOUS and CE-IOUS were compared. Changes in staging or management were noted. Additional lesions were corroborated with iron oxide magnetic resonance imaging (MRI). RESULTS: Among 21 patients, IOUS demonstrated additional lesions in seven (33%). Contrast altered the diagnosis of non-enhanced IOUS in four (20%) and changed the management strategy in three (14%) patients. Thus, IOUS in combination with the contrast agent altered the intraoperative or postoperative management plan in four patients. CONCLUSIONS: In the first study of its kind, early results suggest that the ability of IOUS to detect additional metastases is improved by CE-IOUS, and that this may impact on surgical staging and management. PMID- 20590886 TI - Open liver resection for colorectal metastases: better short- and long-term outcomes in patients potentially suitable for laparoscopic liver resection. AB - BACKGROUND: There is no prospective randomized data comparing laparoscopic to open hepatectomy. This study compared short- and long-term outcomes in patients undergoing hepatectomy for colorectal metastases (CRM), who were suitable for either laparoscopic or open surgery. METHODS: Data were prospectively collected from consecutive patients undergoing hepatic resection of CRM at a single centre (1987-2007). Patients who were suitable for laparoscopic resection (Group 1) were compared with patients whose tumour characteristics would best be considered for open resection (Group 2). RESULTS: Out of 1152 hepatectomies, 266 (23.1%) were deemed suitable for a laparoscopic approach. The median (IQR) number of metastases was greater in Group 2 [2(1-20) vs. 1(1-10), P < 0.001], as was the mean (SD) tumour size [5.3(3.6) cm vs. 3.3(1.2) cm, P < 0.001]. The median (IQR) operation time [210 (70) min vs. 240 (90) min, P < 0.001] and blood loss [270 (265) ml vs. 355 (320) ml, P < 0.001] were less in Group 1. There was no difference in length of stay, morbidity or mortality. Patients in Group 2 had a higher R1 resection rate (14.9%) compared with Group 1 (4.5%, P < 0.001) and lower 5-year survival (37.8% vs. 44.2%, P= 0.005). DISCUSSION: Current criteria for laparoscopic hepatectomy selects patients who have more straight-forward surgery, with less risk of an involved resection margin and better long-term survival, compared with patients unsuited to a laparoscopic approach. Clearly defined criteria for laparoscopic hepatectomy are essential to allow meaningful analysis of outcomes and the results of unrandomized series of laparoscopic hepatectomies must be interpreted with caution. PMID- 20590887 TI - Outcomes in adult recipients of right-sided liver grafts in split-liver procedures. AB - BACKGROUND: The split-liver technique provides a good left lateral graft in children, but its results in adults remain controversial. METHODS: From 1992 to 2007, 37 patients received 38 cadaveric right-sided grafts. Donors and recipients were selected for good quality grafts and elective indications; the latter included a high proportion of tumour cases and primary sclerosing cholangitis. Grafts included 31 extended right grafts (ERGs; segments IV-VIII and I and the inferior vena cava [IVC]) and seven right grafts (RGs; segments V-VIII) including five without the IVC and middle hepatic vein (MHV). RESULTS: Mortality was 5% (two patients). There were four retransplantations (11%) for arterial thrombosis (1), portal vein thrombosis (2) and primary non-function (1). The retransplantation rate was higher in RG than in ERG (three vs. one patient; P= 0.015). Of the five patients without MHV, three were retransplanted and one had small-for-size syndrome leading to late death. After a mean follow-up of 5 years, 1-, 3- and 5-year graft and patient survival rates were 84%, 80% and 71%, and 91%, 88% and 78%, respectively. One-year patient and graft survival rates after ERG transplantation were 96% and 92%, respectively. CONCLUSIONS: Split-liver transplantation is a safe alternative to whole organ transplantation when an ERG is carried out. Right graft is associated with increased risk of graft loss, especially if the MHV is omitted. Split-liver transplantation with an ERG offers excellent outcomes and should be encouraged when good quality grafts are available. PMID- 20590888 TI - A neoadjuvant strategy for pancreatic adenocarcinoma increases the likelihood of receiving all components of care: lessons from a single-institution database. AB - BACKGROUND: Recent studies have shown adjuvant therapy improves outcomes from pancreatic cancer (PC). This study investigates receipt and timing of PC treatments, and association with outcomes. METHODS: The analysis cohort consisted of patients with newly-diagnosed PC at a single institution over 5 years. Primary Endpoints were (i) receipt of recommended therapy, and (ii) overall survival (OS). RESULTS: Among 102 patients, 52 underwent resection. Out of 36 localized resected and 16 locally advanced resected (LAR) patients, 26 and 13, respectively, received adjuvant therapy. Six of the latter group received neoadjuvant therapy. Median OS for resected patients was 15.7 months (range 0.6 51.4), compared with 7.7 for unresected patients (range 0.4-32.0) (P < 0.001), and 14.0 months for patients with resection alone (range 0.6-24.4) vs. 16.1 for patients who also received adjuvant therapy (range 3.2-51.4) (P= 0.027). Out of 46 patients undergoing up-front resection, 33 had R0 surgical margins. For the six LAR patients undergoing neoadjuvant therapy, all margins were R0. CONCLUSION: After resection, a substantial proportion of patients do not receive adjuvant therapy, and have worse survival. In this study, neoadjuvant treatment increased both the proportion of patients receiving all components of recommended therapy and the R0 resection rate. PMID- 20590889 TI - Revision of anastomotic stenosis after pancreatic head resection for chronic pancreatitis: is it futile? AB - BACKGROUND: Because survival after pancreaticoduodenectomy for cancer is limited, it is difficult to assess longterm pancreaticojejunal anastomotic patency. However, in patients with benign disease, pancreaticojejunal anastomotic stenosis may become problematic. What happens when pancreaticojejunal anastomosis revision is undertaken? METHODS: Patients undergoing pancreatic anastomotic revision after pancreatic head resection for benign disease between 1997 and 2007 at the Medical University of South Carolina were identified. A retrospective chart review and analysis were undertaken with the approval of the Institutional Review Board for the Evaluation of Human Subjects. Longterm follow-up was obtained by patient survey at a clinic visit or by telephone. RESULTS: During the study period, 237 patients underwent pancreatic head resection. Of these, 27 patients (17 women; median age 42 years) underwent revision of pancreaticojejunal anastomosis. Six patients (22%) had a pancreatic leak or abscess at the time of the index pancreatic head resection. The indication for revision of anastomosis was intractable pain. All patients underwent preoperative magnetic resonance cholangiopancreatography (MRCP), which indicated anastomotic stricture in 18 patients (63%). Nine other patients underwent exploration based on clinical suspicion caused by recurrent pancreatitis and stenosis was confirmed at the time of surgery. Six patients (22%) had perioperative complications after revision. The median length of stay was 12 days. There were no perioperative deaths; however, late mortality occurred in four patients (15%). Six of 23 survivors (26%) at the time of follow-up (median 56 months) reported longterm pain relief. CONCLUSIONS: Stricture of the pancreaticojejunal anastomosis after pancreatic head resection presents with recurrent pancreatitis and pancreatic pain. MRCP has good specificity in the diagnosis of anastomotic obstruction, but lacks sensitivity. Pancreaticojejunal revision is safe, but rarely effective, as a means of pain relief in patients with the pain syndrome associated with chronic pancreatitis. PMID- 20590890 TI - Liver retransplantation in adults: a single-centre, 25-year experience. AB - BACKGROUND: Retransplantation is the only form of treatment for patients with irreversible graft failure. The aim of this study was to analyse a single centre's experience of the indications for and outcomes of retransplantation. METHODS: A total of 196 patients who underwent liver retransplantation using 225 grafts, between January 1982 and July 2007, were included in the study. The following parameters were analysed: patient demographics; primary diagnosis; distribution of retransplantation over different time periods; indications for retransplantation; time interval to retransplantation, and overall patient and graft survival. RESULTS: Of the 2437 primary orthotopic liver transplantations, 196 patients (8%) required a first regraft, 23 patients (1%) a second regraft and six patients (0.25%) a third regraft. Autoimmune hepatitis was the most common primary diagnosis for which retransplantation was required (12.7% of primary transplantations). The retransplantation rate declined from 12% at the beginning of our programme to 7.6% at the end of the study period. The most common indication for retransplantation was hepatic artery thrombosis (31.6%). Nearly two-thirds of the retransplantations were performed within 6 months of the primary transplantation. The 1-, 3-, 5- and 10-year patient survival rates following first retransplantation were 66%, 61%, 57% and 47%, respectively. Five year survival after second retransplantation was 40%. None of the patients have yet survived 3 years after a third regraft. Donor age of < or =55 years and a MELD (Model for End-stage Liver Disease) score of < or =23 were associated with better outcome following retransplantation. CONCLUSIONS: First retransplantation was associated with good longterm survival. There was no survival benefit following second and third retransplantations. A MELD score of < or =23 and donor age of < or =55 years correlated with better outcome following retransplantation. PMID- 20590891 TI - Image of the month. Annular pancreas. PMID- 20590892 TI - Prognostic scores for colorectal liver metastasis: clinically important or an academic exercise? AB - OBJECTIVES: Over the last decade, various groups have proposed prognostic scoring systems for patients with colorectal liver metastasis (CLM) treated with hepatic resection. The aims of the current study were to evaluate the differences between and clinical importance of these prognostic scoring systems and to determine their clinical applicability. METHODS: Relevant articles were reviewed from the published literature using the MEDLINE database. The search was performed using the keywords 'colorectal cancer', 'metastases', 'liver resection' and 'hepatectomy'. RESULTS: Twelve prognostic scoring systems were identified from 1996 to 2009. Six of these originated from European institutions, three from Asian and three from North American centres. The median study sample was 288 patients (range 81-1568 patients) and median follow-up was 35 months (range 16-52 months). All studies were retrospective in nature and the numbers of groups proposed by the various scoring systems ranged from three to six. All the studies used the Cox proportional hazard model for multi-variable analysis. CONCLUSIONS: There is no 'ideal' prognostic scoring system for the clinical management of patients with CLM for hepatic resection. These prognostic scoring systems are clinically relevant with respect to survival but have not been used for risk stratification in controversial areas such as the administration of chemotherapy or surveillance programmes. PMID- 20590893 TI - Laparoscopic pancreatic surgery: a review of present results and future prospects. AB - Pancreatic surgery is still associated with a relatively high morbidity and mortality compared with other specialties. This is a result of the complex nature of the organ, the difficult access as a result of the retroperitoneal position and the number of technically challenging anastomoses required. Nevertheless, the past two decades have witnessed a steady improvement in morbidity and a decrease in mortality achieved through alterations of technique (particularly relating to the pancreatic anastomoses) together with hormonal manipulation to decrease pancreatic secretions. Recently minimally invasive pancreatic surgery has been attempted by several centres around the world which has stimulated considerable interest in this approach. The majority of the cases attempted have been distal pancreatectomies, because of the more straightforward nature of the resection and the lack of a pancreatic ductal anastomosis, but more recently reports of laparoscopic pancreaticoduodenectomy have started to appear. The reports of the series to date have been difficult to interpret and although the results are claimed to be equivalent or better than those associated with a traditional approach a careful examination of the literature and comparison with the best results previously reported does not presently support this. In the present review we examined all the reports of pancreatic procedures performed laparoscopically and compared the results with those previously achieved at open surgery. PMID- 20590894 TI - What defines 'cure' after liver resection for colorectal metastases? Results after 10 years of follow-up. AB - BACKGROUND: During the last two decades, resection of colorectal liver metastases (CLM) in selected patients has become the standard of care, with 5-year survival rates of 25-58%. Although a substantial number of actual 5-year survivors are reported after resection, 5-year survival rates may be inadequate to evaluate surgical outcomes because a significant number of patients experience a recurrence at some point. OBJECTIVES: This study aimed to analyse longterm results and prognostic factors in liver resection for CLM in patients with complete 10-year follow-up data. METHODS: A total of 369 patients who underwent liver resection for CLM between 1985 and 1998 were identified from a bi institutional database. Postoperative deaths and patients with extrahepatic disease were excluded. Clinicopathological prognostic factors were analysed using univariate and multivariate analyses. RESULTS: The sample included 309 consecutive patients with complete 10-year follow-up data. Five- and 10-year overall survival rates were 32% and 23%, respectively. Overall, 93% of recurrences occurred within the first 5 years of follow-up, but 11% of patients who were disease-free at 5 years developed later recurrence. Multivariate analysis demonstrated four independent negative prognostic factors for survival: more than three metastases; a positive surgical margin; tumour size >5 cm, and a clinical risk score >2. CONCLUSIONS: Five-year survival rates are not adequate to evaluate surgical outcomes of patients with CLM. Approximately one-third of actual 5-year survivors suffer cancer-related death, whereas patients who survive 10 years appear to be cured of disease. PMID- 20590895 TI - Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers. AB - BACKGROUND: Ischaemic preconditioning (IPC) and intermittent ischaemia (INT) reduce liver injury after ischaemia reperfusion (IR). Steatotic livers are at a higher risk of IR injury, but the protection offered by IPC and INT is not well understood. The aim of the present study was to determine the effectiveness of IPC and INT in maintaining liver function in steatotic livers. MATERIAL AND METHODS: A model of segmental hepatic ischaemia (45 min) and reperfusion (60 min) was employed using lean and obese Zucker rats. Bile flow recovery was measured to assess dynamic liver function, hepatocyte fat content quantified and blood electrolytes, metabolites and bile calcium measured to assess liver and whole body physiology. Liver marker enzymes and light and electron microscopy were employed to assess hepatocyte injury. RESULTS: IPC was not effective in promoting bile flow recovery after IR in either lean or steatotic livers, whereas INT promoted good bile flow recovery in steatotic as well as lean livers. However, the bile flow recovery in steatotic livers was less than that in lean livers. In steatotic livers, ischaemia led to a rapid and substantial decrease in fat content. Steatotic livers were more susceptible to IR injury than lean livers, as indicated by increased blood ALT concentrations and major histological injury. CONCLUSION: INT is more effective than IPC in restoring liver function in the acute phase of IR in steatotic livers. In obese patients, INT may be useful in promoting better liver function after IR after liver resection. PMID- 20590897 TI - Index admission laparoscopic cholecystectomy for patients with acute biliary symptoms: results from a specialist centre. AB - BACKGROUND: Index admission laparoscopic cholecystectomy (ALC) is the treatment of choice for patients admitted with biliary symptoms but is performed in less than 15% of these admissions. We analysed our results for ALC within a tertiary hepatobiliary centre. METHODS: Data from all cholecystectomies carried out under the care of the two senior authors from 1998 to 2008 were prospectively collected and interrogated. RESULTS: 1710 patients underwent cholecystectomy of which 439 (26%) were ALC. Patients operated on acutely did not have a significantly different complication rate (P= 0.279; 4% vs.3%). Factors predicting complications were abnormal alkaline phosphatase (ALP) (P= 0.037), dilated common bile duct (CBD) (P= 0.026), cholangitis (P= 0.040) and absence of on table cholangiography (OTC) (P= 0.011). There were no bile duct injuries. Patients undergoing ALC had a higher rate of conversion to an open procedure (P < 0.001:10% vs.3%). The proportion of complicated disease was higher in the ALC group (P < 0.001; 70% vs.31%). Only complicated disease (P= 0.006), absence of OTC (P < 0.001) and age greater than 65 years (P < 0.001) were predictive of conversion on multivariate analysis. CONCLUSIONS: Laparoscopic cholecystectomy can be performed safely in patients with acute biliary symptoms and should be considered the gold standard for management of these patients thus avoiding avoidable readmissions and life-threatening complications. A higher conversion rate to an open procedure must be accepted when treating more complicated disease. It is the severity of disease rather than timing of surgery which most probably predicts complications and conversions. PMID- 20590896 TI - Two-stage strategy for patients with extensive bilateral colorectal liver metastases. AB - BACKGROUND: Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases. The present study assesses the feasibility and outcome of two-stage hepatectomy for the treatment of colorectal liver metastases. METHODS: From January 1994 to December 2008, 720 patients underwent liver resections at two institutions for colorectal liver metastases. The feasibility and outcomes of two-staged hepatectomies were evaluated. RESULTS: Forty-five patients were eligible for the two-stage approach and both stages were completed in 35 patients (78%). Reasons for failure included disease progression (n= 7), poor performance status (n= 1) and death after the first stage (n= 2). Patients who completed both stages had significantly fewer lesions than patients who failed to complete the second stage (5 vs. 8; P= 0.02). No differences between the two groups were observed with regard to lesion size, receipt of radiofrequency ablation (RFA) or presence of extrahepatic disease. Post-operative morbidity (24% vs. 26%; P= 0.9) and mortality (4% vs. 5%; P= 0.8) was similar between the first and second stages. Median overall survival was 16 months. Three year survival was significantly worse for patients failing to complete both stages (18%) compared with patients completing both stages (58%) (P < 0.001). Similar survival rates were observed between patients who completed two-stage vs. patients treated with a planned single-stage hepatectomy (58% vs. 53%; P= 0.34). CONCLUSION: The two-stage strategy for colorectal liver metastases can be performed with acceptable morbidity and mortality. The second stage will not be feasible in 20-25% of patients. Patients who are able to complete the two-stage approach, however, may have long-term survival comparable to patients treated with a planned single-stage hepatectomy. PMID- 20590899 TI - Type IV A choledochal cyst with cystic duct cyst. PMID- 20590898 TI - Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. AB - BACKGROUND: The complete resection of liver metastases from colorectal cancer is the major determinant of longterm survival. The effectiveness of current chemotherapy regimens has made treatment algorithms more flexible and resulted in many different options. Recently, the pathological response to chemotherapy has emerged as another important prognostic marker. Different systems have been used to grade the pathological response in these patients. METHODS: This study prospectively evaluates the prognostic value of the pathological response grade (PRG) in liver metastases treated with neoadjuvant chemotherapy. RESULTS: Between 2002 and 2006, 50 patients were treated with a sandwich chemotherapy regimen and underwent liver resection. Complete resection was achieved in 45 patients (90%). A strong pathological response to chemotherapy (<10% viable tumour cells in all lesions) was seen in 17 patients (34%). It was associated with a statistically significant longer overall survival (P= 0.019) and was also identified on multivariate analysis as an independent predictor of survival (odds ratio = 243). CONCLUSIONS: This pilot study demonstrates the prognostic potential of the PRG, which could be used clinically to select patients for an aggressive multimodal adjuvant algorithm. Larger multicentre studies are required to validate this particular grading system. The keys to longterm survival are resectability and chemo-responsiveness. PMID- 20590900 TI - AHPBA/SSO/SSAT sponsored Consensus Conference on Multidisciplinary Treatment of Hepatocellular Carcinoma. PMID- 20590901 TI - Pretreatment assessment of hepatocellular carcinoma: expert consensus statement. AB - Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize < 1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (<= 20% in normal liver; <= 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease. PMID- 20590902 TI - Pretreatment assessment of hepatocellular cancer: expert consensus conference. PMID- 20590903 TI - Surgical treatment of hepatocellular carcinoma: expert consensus statement. AB - As the number of effective treatment options has increased, the management of patients with hepatocellular carcinoma has become complex. The most appropriate therapy depends largely on the functional status of the underlying liver. In patients with advanced cirrhosis and tumor extent within the Milan criteria, liver transplantation is clearly the best option, as this therapy treats the cancer along with the underlying hepatic parenchymal disease. As the results of transplantation has become established in patients with limited disease, investigation has increasingly focused on downstaging patients with disease outside of Milan criteria and defining the upper limits of transplantable tumors. In patients with well preserved hepatic function, liver resection is the most appropriate and effective treatment. Hepatic resection is not as constrained by tumor extent and location to the same degree as transplantation and ablative therapies. Some patients who recur after resection may still be eligible for transplantation. Ablative therapies, particularly percutaneous radiofrequency ablation and transarterial chemoembolization have been used primarily to treat patients with low volume irresectable tumors. Whether ablation of small tumors provides long term disease control that is comparable to resection remains unclear. PMID- 20590904 TI - Surgical treatment of hepatocellular cancer: expert consensus conference. PMID- 20590905 TI - Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement. AB - Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options. PMID- 20590906 TI - Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus conference. PMID- 20590907 TI - Cachexia in pancreatic cancer: new treatment options and measures of success. PMID- 20590908 TI - Preoperative body composition is influenced by the stage of operable pancreatic adenocarcinoma but does not predict survival after Whipple's procedure. AB - OBJECTIVES: Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore, this study was carried out to document body composition status in patients with pancreatic adenocarcinoma (PCa) presenting for a Whipple's procedure (WP) and to relate the findings to histopathology and longterm survival. METHODS: Body composition was measured 1 day before a WP for ductal PCa in 36 patients (15 men, 21 women) aged 41-81 years. Results for total body nitrogen (TBN), nitrogen index (NI), total body water (TBW), fat mass (FM) and total body potassium (TBK) were compared with results in 73 age- and sex matched controls. Patients' survival and details from histopathology synoptic reports were documented. RESULTS: Patients undergoing WPs had low TBK values (P < 0.001) and females had lower body fat (P = 0.007) compared with controls. Five of 36 presented with significant protein deficiency, but this was not associated with a prolonged length of stay or reduced survival. The 12 patients who had involved surgical margins had larger tumours and reduced weight (P = 0.015), FM (P = 0.001), TBN (P = 0.045), TBK (P = 0.014) and survival (P = 0.036). However, multivariate Cox's regression analysis only included FM along with vascular invasion and margin status as independent predictors of survival. CONCLUSIONS: PCa patients undergoing a WP have reduced body fat and TBK compared with community controls while those with stage III tumours had greater deficits of fat, TBK and protein stores. However, preoperative body composition was a poor predictor of postoperative survival after pathological data were considered. PMID- 20590910 TI - Alanine transaminase rather than abdominal ultrasound alone is an important investigation to justify cholecystectomy in patients presenting with acute pancreatitis. AB - OBJECTIVES: The aims of this study were to investigate the predictive value of an elevated level of alanine transaminase (ALT) for biliary acute pancreatitis (AP) and to reconsider the role of abdominal ultrasound (AUS). METHODS: All patients admitted to Christchurch Public Hospital with AP between July 2005 and December 2008 were identified from a prospectively collected database. Peak ALT within 48 h of presentation was recorded. Aetiology was determined on the basis of history, AUS and other relevant investigations. RESULTS: A total of 543 patients met the inclusion criteria. Patients with biliary AP had significantly higher median (range) ALT than those with non-biliary causes (200 units/l [63-421 units/l] vs. 33 units/l [18-84 units/l]; P < 0.001). An ALT level of >300 units/l had a sensitivity of 36%, specificity of 94%, positive predictive value of 87% and positive likelihood ratio of 5.6 for gallstones. An elevated ALT and negative AUS had a probability of 21-80% for gallstones. CONCLUSIONS: An elevated ALT strongly supports a diagnosis of gallstones in AP. Abdominal ultrasound effectively confirms this diagnosis; however, a negative ultrasound in the presence of a raised ALT does not exclude gallstones. In some patients consideration could be given to proceeding to laparoscopic cholecystectomy based on ALT alone. PMID- 20590909 TI - Hepatic resection for post-cholecystectomy bile duct injuries: a literature review. AB - OBJECTIVES: This study seeks to identify factors for hepatectomy in the management of post-cholecystectomy bile duct injury (BDI) and outcome via a systematic review of the literature. METHODS: Relevant literature was found by searching the PubMed database and the bibliographies of extracted articles. To avoid bias selection, factors for hepatectomy were analysed in series reporting both patients undergoing hepatectomy and patients undergoing biliary repair without hepatectomy (bimodal treatment). Relevant variables were the presence or absence of additional hepatic artery and/or portal vein injury, the level of BDI, and a previous biliary repair. RESULTS: Among 460 potentially relevant publications, only 31 met the eligibility criteria. A total of 99 hepatectomies were reported among 1756 (5.6%) patients referred for post-cholecystectomy BDI. In eight series reporting bimodal treatment, including 232 patients, logistic regression multivariate analysis showed that hepatic arterial and Strasberg E4 and E5 injuries were independent factors associated with hepatectomy. Patients with combined arterial and Strasberg E4 or E5 injury were 43.3 times more likely to undergo hepatectomy (95% confidence interval 8.0-234.2) than patients without complex injury. Despite high postoperative morbidity, mortality rates were comparable with those of hepaticojejunostomy, except in urgent hepatectomies (within 2 weeks; four of nine patients died). Longterm outcome was satisfactory in 12 of 18 patients in the largest series. CONCLUSIONS: Hepatectomies were performed mainly in patients showing complex concurrent Strasberg E4 or E5 and hepatic arterial injury and provided satisfactory longterm outcomes despite high postoperative morbidity. PMID- 20590911 TI - Irreversible electroporation of the pancreas in swine: a pilot study. AB - BACKGROUND: Irreversible electroporation (IRE) is a novel, non-thermal method of tissue ablation using short pulses of high-voltage DC current to ablate tissue. METHODS: Irreversible electroporation of the pancreas was performed in four domestic female swine using two monopolar probes spaced 9-15 mm apart. Ninety pulses of 1500 V/cm were delivered for each ablation. RESULTS: All animals survived for their designated times of 2 h (n = 1), 2 days (n = 1) and 14 days (n = 2), respectively. No procedure-related complications occurred. Three animals in which probes had been spaced at intervals of 10 +/- 1 mm showed evidence of irreversible ablation, with ablation height ranging from < 10 mm to 21 mm and ablation width ranging from < 10 mm to 16 mm by gross appearance and triphenyltetrazolium chloride (TTC) staining. The only animal in which probes had been spaced at intervals of 15 mm did not show evidence of irreversible ablation at 2 weeks. This may be secondary to the wider probe spacing and relatively low voltage, which results in a mostly reversible form of electroporation without cell death. CONCLUSIONS: Irreversible electroporation appears to be a safe method for pancreas tissue ablation. Staining with TTC can predict the zone of IRE ablation within 2 h of treatment. PMID- 20590912 TI - Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma. AB - OBJECTIVE: Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA. METHODS: Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival. RESULTS: In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival. CONCLUSIONS: Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation. PMID- 20590914 TI - In vitro organogenesis using multipotent cells. AB - Abstract The establishment of efficient methods for promoting stem cell differentiation into target cells is important not only in regenerative medicine, but also in drug discovery. In addition to embryonic stem (ES) cells and various somatic stem cells, such as mesenchymal stem cells derived from bone marrow, adipose tissue, and umbilical cord blood, a novel dedifferentiation technology that allows the generation of induced pluripotent stem (iPS) cells has been recently developed. Although an increasing number of stem cell populations are being described, there remains a lack of protocols for driving the differentiation of these cells. Regeneration of organs from stem cells in vitro requires precise blueprints for each differentiation step. To date, studies using various model organisms, such as zebrafish, Xenopus laevis, and gene-targeted mice, have uncovered several factors that are critical for the development of organs. We have been using X. laevis, the African clawed frog, which has developmental patterns similar to those seen in humans. Moreover, Xenopus embryos are excellent research tools for the development of differentiation protocols, since they are available in high numbers and are sufficiently large and robust for culturing after simple microsurgery. In addition, Xenopus eggs are fertilized externally, and all stages of the embryo are easily accessible, making it relatively easy to study the functions of individual gene products during organogenesis using microinjection into embryonic cells. In the present review, we provide examples of methods for in vitro organ formation that use undifferentiated Xenopus cells. We also describe the application of amphibian differentiation protocols to mammalian stem cells, so as to facilitate the development of efficient methodologies for in vitro differentiation. PMID- 20590915 TI - Novel amelanotic and melanotic cell lines NM78-AM and NM78-MM derived from a human oral malignant melanoma. AB - Abstract Novel cell lines, designated NM78-AM and NM78-MM, have been established from a malignant melanoma of the cheek oral mucosa. NM78-AM cells were spherical, grew in suspension as clusters, and produced no melanin. In contrast, NM78-MM cells were adherent and produced melanin granules. Initially, NM78-AM cells were grown on fibroblast feeder cells or in growth media supplemented with 10% conditioned medium from fibroblasts, but eventually grew in standard growth media alone. NM78-AM cells had interdigitating microvilli and formed cell clusters. They had large nucleoli, desmosomes, lipid droplets, and well-developed Golgi apparatuses. In contrast, NM78-MM cells grew as adherent neuron-like cells. They had large prominent nucleoli, irregular nuclear membranes, a number of mitochondria, well-developed Golgi apparatuses, melanosomes at various stages of development in the cytoplasm, and the cells secreted melanin granules. Projections from these melanotic cells formed anastomoses with each other. NM78 MM cells stained immunofluorescently for internexin, neuron specific enolase, NF 200, and glial fibrillary acidic protein. These cells were severely aneuploid, approximating to triploidy, and had many marker chromosomes. We used a real-time monitoring system to evaluate oxygen concentrations in culture medium to investigate the susceptibility of both cell lines to various anti-cancer drugs. NM78-AM cells were slightly sensitive to actinomycin D, but not to cisplatin, irinotecan, the irinotecan metabolite SN-38, taxol, taxotere, bleomycin and methotrexate; NM78-MM cells were sensitive to cisplatin, and not to taxol, taxotere, carboplatin, and irinotecan. These new cell lines, NM78-AM and NM78-MM, will be very important for the development of new chemotherapeutics for oral malignant melanoma. PMID- 20590916 TI - Heterotopic autotransplantation of ovarian cortex in cynomolgus monkeys. AB - Abstract In recent years, removal of ova or ovaries before chemotherapy or radiation therapy has been investigated in young female cancer patients to avoid the adverse effects of treatment. Orthotopic autotransplantation of ovarian cortex has advantages such as easy collection of ova and the possibility of spontaneous pregnancy. Although children have been born after successful orthotopic autotransplantation into the residual ovaries, some patients cannot undergo this procedure such as those who need bilateral ovariectomy or pelvic radiation therapy, therefore it is still necessary to investigate suitable heterotopic autotransplantation sites. The present study was performed in primates (cynomolgus monkeys) with the objective of determining the optimum site for heterotopic autotransplantation of ovarian cortex to enhance the clinical application of this method. The retroperitoneal iliac fossa and omentum were selected as sites for heterotopic autotransplantation. Two cynomolgus monkeys were subjected to laparotomy under anesthesia. After resection of the bilateral adnexae, the ovaries were cut into 0.5 cm cubes that were transplanted. Blood levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were monitored, and monkeys with a regular estrus cycle underwent superovulation and egg collection. In both monkeys studied, recovery of a regular estrus cycle was confirmed after heterotopic autotransplantation of ovarian tissue. MII phase ova were successfully collected from tissues transplanted into the retroperitoneal iliac fossa or omentum. Development to the early blastocyst stage was confirmed after microfertilization. We established an appropriate method of heterotopic autotransplantation using ovarian cortex into the retroperitoneal iliac fossa or omentum in primates. PMID- 20590917 TI - Air quality influence on chronic obstructive pulmonary disease (COPD) patients' quality of life. AB - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death. The relationship between urban air pollution and its short-term health effects on patients suffering from COPD is confirmed. However, information about the impact of air pollutants upon the quality of life (QOL) in patients with COPD is lacking. Through a cross-sectional survey, this study investigates such impact in terms of the scores of the (Chinese) chronic respiratory questionnaire (CCRQ) and the measurements of indoor air quality (IAQ), lung function and Moser's activities of daily living (ADL). Using Yule's Q statistic with a cutoff |Q|>0.7 to identify the strong relationships between environmental parameters and CRQ sub scores, this study reveals that patient emotion is strongly associated with indoor environmental quality although the evidence of a causal relationship between them needs further research. PRACTICAL IMPLICATIONS: As QOL in patients with COPD and indoor environmental parameters are strongly associated, indoor air pollutants must be monitored for related studies in the future. PMID- 20590918 TI - A dose-dependent relationship between the severity of visible mold growth and IgE levels of pre-school-aged resident children in Taiwan. AB - To demonstrate a dose-dependent relationship between severity of indoor visible mold growth and serum total IgE levels of resident children. A total of 97 children (4-7 years old) identified from previously established birth-cohort, with information pertaining to indoor environmental conditions after child's birth, were successfully recruited while sera were concurrently collected for total IgE and specific IgE analysis during clinical visits. Severity of visible mold growth at homes was scaled into three levels accordingly. A statistically significant dose-dependent relationship was found between severity of indoor visible mold growth and total serum IgE levels. The trend sustains after the model was adjusted for resident child's age, gender, pet-keeping history, number of siblings, atopic history of parents, presence of incense burning, and environmental tobacco smoking (ETS) at home. Further analysis of specific IgE to commonly examined fungal allergens did not substantiate the correlation. Rather, resident child's specific IgE to mite allergens, although without statistical significance, seemed to better associate with the ranked severity of indoor mold growth in this study. An adjuvant role of fungal exposure to enhance sensitization in indoor environment is therefore suggested in Taiwanese population with high prevalence of building dampness. PRACTICAL IMPLICATIONS: The presence of indoor visible mold growth, potentially resulting in fungal exposure, was not associated directly with changing biomarker levels of allergic response in resident children, rather playing an adjuvant role to enhance sensitization. On the other hand, other allergens, such as mite allergen examined in this study, appeared to support a more plausible etiology for directly triggering the ultimate allergic symptoms and diseases of interest. Evidence as such may derive different priority-setting when designing preventive measures for managing indoor air quality. PMID- 20590919 TI - A comparison of the allergic responses induced by Penicillium chrysogenum and house dust mite extracts in a mouse model. AB - A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. We compared the ability of the fungal Penicillium chrysogenum (PCE) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration (IA) at several doses (0, 2.5, 5, 10, 20, 40, and 80 MUg) four times over a 4-week period. Three days after the last IA exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The relative allergenicity of the extracts was evaluated based on the lowest dose able to induce a significant response compared to control (0 MUg) and the robustness of the response. PCE induced the most robust response at the lowest dose for most endpoints examined: BALF total, macrophage, neutrophil, and eosinophil cell counts, and antigen-specific IgE. Taken together, our data suggest that PCE may induce a more robust allergic and inflammatory response at lower doses than HDM. PRACTICAL IMPLICATIONS: Our data suggest that Penicillium chrysogenum is a robust allergen and may be a more potent allergen source than house dust mite (HDM) in this mouse model. Two critical factors in the development of human allergic disease, exposure levels and sensitization thresholds, are unknown for most allergens including molds/fungi. Human exposure levels are not within the scope of this article. However, the data presented suggest a threshold dose for the induction of allergic responsiveness to P. chrysogenum. Additionally, P. chrysogenum as well as other molds may play an important role in asthma development in our society. PMID- 20590920 TI - Measured concentrations of combustion gases from the use of unvented gas fireplaces. AB - Measurements of combustion product concentrations were taken in 30 homes where unvented gas fireplaces were used. Measurements of CO, CO(2), NO(x), NO(2) , O(2) (depletion), and water vapor were taken at 1-min interval. The analyzers were calibrated with certified calibration gases for each placement and were in operation for 3-4 days at each home. Measured concentrations were compared to published health-based standards and guidelines. The two combustion gases that exceeded published values were NO(2) and CO. For NO(2) , the Health Canada guideline of 250 ppb (1-h average) was exceeded in about 43% of the sample and the World Health Organization (WHO) guideline of 110 ppb (1-h average) was exceeded in 80% of the sample. Carbon monoxide levels exceeded the U.S. EPA 8-h average standard of 9 ppm in 20% of the sample. Moisture problems were not evident in the test homes. An analysis of the distribution of CO showed that the CO is dispersed throughout the home almost immediately upon operation of the fireplace and that the concentrations throughout the home away from the immediate vicinity of the fireplace are 70-80% of the level near the fireplace. Decay analysis of the combustion gases showed that NO was similarly stable to CO and CO(2) in the indoor environment but that both NO(2) and water vapor were removed from the air at much greater rates. PRACTICAL IMPLICATIONS: Previous studies on unvented gas fireplaces have made assumptions of how they are operated by users. This article presents the results of field monitoring of 30 unvented gas fireplaces under normal operation, regardless of whether users follow industry recommendations regarding installation, usage patterns, and maintenance. The monitoring found that health-based standards and guidelines were exceeded for CO in 20% of homes and for NO(2) in most homes. There were no identified moisture problems in these homes. Nearly, half of the fireplaces were used at least once for longer than 2 h, counter to manufacturers' intended usage as supplemental heating. This demonstrates that given actual usage patterns and compared to current health-based thresholds, these appliances can produce indoor air concentrations considered to be unhealthy to at least sensitive or at-risk individuals. PMID- 20590921 TI - Letter from Paris. PMID- 20590922 TI - La vita nuova. PMID- 20590923 TI - La vita nuova analysis. PMID- 20590924 TI - Commentary on the material presented by Ingrid M. Geerken: a new discourse, a new love. PMID- 20590925 TI - Notes on the beating fantasy. AB - This theoretical paper revisits the beating fantasy, which constitutes a crossroads of the psychic economy in that it condenses three primal phantasies, namely the primal scene, castration and seduction. Two forms of the phantasy have been distinguished: a 'fixed' form, apparently associated with the masochistic perversion, and a 'transitory' form, probably bound up with libidinal development. In Freud 's (1919) paper these two aspects are intertwined. The present contribution confines itself to the transitory form of the phantasy and its significance in the libidinal development of the girl, notably in the organization of passivity. With this in mind, particular attention is paid to the phantasy's third phase in this context, and an attempt made to show how this phase epitomizes the transformation of the instinctual pressure and might therefore be looked upon in this connection as the intermediate phase of the phantasy. PMID- 20590926 TI - From Freud's dream-work to Bion's work of dreaming: the changing conception of dreaming in psychoanalytic theory. AB - Bion moved psychoanalytic theory from Freud's theory of dream-work to a concept of dreaming in which dreaming is the central aspect of all emotional functioning. In this paper, I first review historical, theoretical, and clinical aspects of dreaming as seen by Freud and Bion. I then propose two interconnected ideas that I believe reflect Bion's split from Freud regarding the understanding of dreaming. Bion believed that all dreams are psychological works in progress and at one point suggested that all dreams contain elements that are akin to visual hallucinations. I explore and elaborate Bion's ideas that all dreams contain aspects of emotional experience that are too disturbing to be dreamt, and that, in analysis, the patient brings a dream with the hope of receiving the analyst's help in completing the unconscious work that was entirely or partially too disturbing for the patient to dream on his own. Freud views dreams as mental phenomena with which to understand how the mind functions, but believes that dreams are solely the 'guardians of sleep,' and not, in themselves, vehicles for unconscious psychological work and growth until they are interpreted by the analyst. Bion extends Freud's ideas, but also departs from Freud and re-conceives of dreaming as synonymous with unconscious emotional thinking - a process that continues both while we are awake and while we are asleep. From another somewhat puzzling perspective, he views dreams solely as manifestations of what the dreamer is unable to think. PMID- 20590927 TI - The Italian Red Brigades and the structure and dynamics of terrorist groups. AB - One of the problems in dealing with terrorism is that we have virtually no access to individual terrorists; only their actions are visible. The founders of the Italian terrorist group, the Red Brigades, on the other hand, have written about their experiences and have exhaustively explained their motivations. The author's premise is that these autobiographies and her interviews with several of the group's members give us access to the unconscious processes involved in the formation and operation of the group. After terrorist attacks, it is natural to ask whether the terrorists' capacity for collective violence is an indication of personal pathology. This paper argues that the relevant pathology in the terrorist enterprise is not that of the individual but that of the group. Relying on the theories of groups of Freud (1921), Bion (1961), Anzieu (1984) and Kaes (2007), the author argues that psychoanalytic theory is essential to understanding the motivations and actions of violent groups which otherwise remain obscure. Although the discussion has been confined to one terrorist group, the author hopes that it can also be useful for understanding the unconscious dynamics of other groups structured around an ideology which mandates the destruction of human life. PMID- 20590928 TI - One-person and two-person conceptions of attachment and their implications for psychoanalytic thought. AB - There has been increasing interest among analysts in the possibilities of enriching psychoanalytic thought through fuller incorporation of attachment theory and research. This paper offers a clinical illustration of the ways in which attention to an attachment perspective can lead to novel and useful ways of addressing the patient's issues. It also presents a number of cautions that it is necessary to be alert to if attachment thinking is to achieve its full potential in advancing psychoanalytic thought and practice. Conceptions of attachment and approaches to its study and clinical use actually vary quite substantially. Some are more one-person, static, and categorical. Others are more two-person, dynamic, and focused on the process whereby attachment patterns develop and are maintained over time. This paper explores the distinction between these two versions of attachment theory and research with two aims in mind - first, to refine our understanding of the potential role that attachment thinking can play in advancing the psychoanalytic paradigm; second, to utilize the insights achieved through examining the attachment paradigm to consider some broader issues in the construction of psychoanalytic theory more generally and its relational variant in particular. PMID- 20590929 TI - Two modalities of manic defences: their function in adolescent breakdown. AB - The aim of this paper is to explore two different modalities of manic defences and their specific underlying anxieties. I will describe the relation between these defences and the role of the superego and their specific function in adolescent breakdown. While one type of manic defence operates by the ego's identification with a sadistic superego the other one operates via evacuation of a guilt-inducing superego. I will illustrate the proposed ideas with clinical examples from the analysis of two adolescents. This paper stresses the specific differences between these two modalities and the clinical importance of both identifying and addressing the enactment in the transference of the unconscious phantasies and anxieties (paranoid and depressive) that give rise to these two types of defences. PMID- 20590930 TI - Some observations on the process of mourning. AB - The main proposal of this paper is that normal mourning is not completed after six months to a year or two as suggested in earlier literature, but may bring about a permanent alteration of psychological structures that affect various aspects of the mourning persons' lives. These structural consequences of mourning consist in the setting up of a persistent internalized object relationship with the lost object that affects ego and superego functions. The persistent internalized object relationship develops in parallel to the identification with the lost object, and the superego modification includes the internalization of the value systems and life project of the lost object. A new dimension of spiritual orientation, the search for transcendental value systems, is one consequence of this superego modification. PMID- 20590931 TI - Conceptual framework from the Paris Psychosomatic School: a clinical psychoanalytic approach to oncology. AB - This article presents further clinical material from the Paris Psychosomatic School (Aisenstein, 2006). The Freudian foundations of psychosomatics are detailed and post-Freudian developments focusing on the contribution of the Paris Psychosomatic School are outlined, in particular, the somatizing process as a result of regression and the somatizing process as a result of drive unbinding. The authors argue that the latter possibly gives rise to progressive and serious illness leading to death. The relationship of classical psychoanalysis to psychotherapeutic treatment from the angle of the Paris school is commented on. The authors then turn to two clinical presentations of women suffering from breast cancer. The method of evaluating the patients' capacities for undergoing psychotherapeutic treatment and their mental capacity for healing is discussed. The face-to-face psychoanalytic treatment undertaken with the second case is discussed. Finally, the authors recall Freud's insistence after 1920 on the opposition of the life drives and the death drives, which placed self-destruction at the centre of psychic functioning. They conclude that current research in biology and medicine, notably research concerning programmed cell death, will converge with psychoanalytic psychosomatics to illuminate somatizing processes and demonstrate the relevance of psychoanalytic treatment to patients who are capable of mental reorganization in the course of their illness and medical treatment. PMID- 20590932 TI - On: the concept of death drive and aggression. PMID- 20590933 TI - The Curious Case of Benjamin Button: regression and the angel of death. PMID- 20590940 TI - Characteristics and management of erectile dysfunction after various treatments for prostate cancer. PMID- 20590942 TI - Molecular pathology of chromophobe renal cell carcinoma: a review. AB - The recognition of chromophobe renal cell carcinoma (RCC) among other distinct types of renal cell tumors (RCT) based on light-microscopic features, such as cytoplasmic and nuclear characteristics, might pose a dilemma in some cases because of morphological pattern overlapping with renal oncocytoma or conventional RCC. The present article reviews chromophobe RCC with focus on aspects of its molecular pathology, which was shown using ancillary modern microarray-based technology that can distinguish it from its mimics and therefore be helpful for its correct diagnosis. Although the high resolution DNA-microarray analyses excluded with all certainty the occurrence of small specific alterations, the loss of entire chromosomes 2, 10, 13, 17 and 21 occurs exclusively in chromophobe RCC and therefore probes localized at these chromosomes might be used to establish the diagnosis of chromophobe RCC in cases with uncertain histology. The usefulness of proposed candidate genes selected by the global gene expression analyses in the diagnostic pathology is far below expectations. The conflicting staining patterns, together with the poor specificity of used antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of chromophobe RCC, with the exception of CD82, which has recently been suggested to be used for routine histological diagnosis. PMID- 20590943 TI - Editorial comment to molecular pathology of chromophobe renal cell carcinoma: a review. PMID- 20590944 TI - Molecular pathology of renal oncocytoma: a review. AB - Differentiating renal oncocytoma from its renal cell carcinoma (RCC) mimics, particularly chromophobe RCC, can be difficult, especially when limited tissue is available for evaluation and requires sophisticated microscopic, ultrastructural and immunohistochemical evaluation. In this review, the relevant literature has been reviewed, and supporting data obtained by applying modern microarray-based technologies are discussed with a focus on molecular pathology of renal oncocytoma. The high resolution whole-genome DNA-microarray based analyses excluded with all certainty the occurrence of small specific alterations. Renal oncocytomas are characterized by variable chromosomal patterns. The number of genes selected by global gene expression analyses and their usefulness in the diagnostic pathology based on immunohistochemical evaluation is far below the expectations. The conflicting staining patterns, together with the poor specificity of proposed antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of these tumors. Applying DNA based tools might help in the diagnosis of renal oncocytoma with uncertain histology. However, only the combination of all available techniques could give reliable information. PMID- 20590945 TI - Editorial comment from Dr Young to Molecular pathology of renal oncocytoma: A review. PMID- 20590946 TI - Editorial comment from Dr Picken to Molecular pathology of renal oncocytoma: a review. PMID- 20590947 TI - Editorial comment to Pattern of intravesical recurrence after surgical treatment for urothelial cancer of the upper urinary tract: a single institutional retrospective long-term follow-up study. PMID- 20590948 TI - Editorial comment from Dr Lallas to robotic-assisted laparoscopic radical prostatectomy: learning curve of first 100 cases. PMID- 20590949 TI - Editorial comment to efficacy of endoscopic subureteral injection for vesicoureteral reflux in adults with decreased bladder compliance. PMID- 20590950 TI - Editorial comment to effect of dominant hemispheric stroke on detrusor function in patients with lower urinary tract symptoms. PMID- 20590952 TI - One year seems like 25 years and 25 years seems like one. PMID- 20590953 TI - Clinical practice guidelines for pediatric constipation. AB - PURPOSE: To discuss the diagnosis and management of pediatric constipation by nurse practitioners in primary care. DATA SOURCES: Clinical practice guidelines and selected research articles. CONCLUSIONS: Pediatric constipation is a common complaint. Few children have an organic cause; more common is "functional constipation." Management may include medications, dietary interventions, and behavior modification. Patient and family education is essential. IMPLICATIONS FOR PRACTICE: A successful outcome requires multiple management strategies. There are usually relapses and gradual progress, so follow-up is essential. A consult with a pediatric gastroenterologist is indicated when treatment fails, if there is concern about an organic cause, or for complex management. PMID- 20590954 TI - Improving nurse practitioner assessment of woman veterans. AB - PURPOSE: To provide nurse practitioners (NPs) with brief screening tools that can be used to identify postmilitary healthcare concerns common among women veterans. DATA SOURCES: Existing screening tools for posttraumatic stress disorder, traumatic brain injury, and military sexual trauma. CONCLUSIONS: Women represent more than 10% of military veterans who have served in combat settings during the current wars in Afghanistan and Iraq. As a result of their military service, women veterans may present in community healthcare settings with one or more of a variety of functional health problems, posttraumatic stress disorder, depression, anxiety, or other evidence of significant physical or psychiatric stress. Their families may be temporarily or permanently unstable as a result of the disruption caused by their military service, deployment, or health status. IMPLICATIONS FOR PRACTICE: NPs who are aware of the unique healthcare needs of women veterans returning from combat will be better prepared to assess and intervene when these patients present with symptoms or health consequences of military service. Simple, straightforward assessments can determine the extent to which women veteran patients require intervention during wartime and/or referral. PMID- 20590955 TI - Making the diagnosis: idiopathic rapid eye movement sleep behavior disorder. AB - PURPOSE: To present a clinical case of idiopathic rapid eye movement sleep behavior disorder (RBD), differential diagnoses, selected treatments, and the pathology involved. DATA SOURCES: An Ovid data base search (covering 635 medical, neurologic, and psychiatric journals) was conducted using the search term RBD and limited to the years 2005-2009. This search strategy was used to locate clinical, research, and review articles providing the state of the science about RBD. A hand search was also conducted for seminal research papers as well as recent publications within the specialty of sleep disorders. CONCLUSIONS: RBD is a parasomnia with symptoms common to other disorders making it important to identify unique symptoms and diagnostic testing that helps differentiates these diseases. RBD can put the patient and the bed partner at risk for injury. Its prevalence is estimated to be 0.5% in older adults. IMPLICATIONS FOR PRACTICE: Nurse practitioners are primary care providers for older adults who may have complaints about behaviors associated with RBD. Knowledge of this disease process as well as its relationship with four other neurodegenerative diseases may provide an opportunity for early diagnosis and treatment of RBD and surveillance for and early diagnosis of the other neurodegenerative diseases in these patients. PMID- 20590956 TI - Emergency department ultrasound by nurse practitioners. AB - PURPOSE: Bedside ultrasound (u/s) examinations by emergency physicians (EPs) have been integrated into clinical emergency medicine (EM) training programs and the efficacy and success of an introductory u/s training course, based on established guidelines, has been previously described. We used this same course to teach EM nurse practitioners (NPs) bedside u/s and then assessed the adequacy of NP ultrasonography 1 year following the course. DATA SOURCES: Five NPs were included in a standardized 16-h EM u/s training program. Subsequently, the NPs were asked to print consecutive u/s images representative of their clinical assessments. A single qualified EP reviewer assessed images for adequacy. CONCLUSIONS: Five NPs reported 229 u/s examinations, two of which were excluded as nondiagnostic over the 2-month study period. There were 32 inadequate images and 27 "positive" findings. All the positives were correct. Totals per provider were 104, 58, 49, 13, and 3 u/s assessments with 83%, 95%, 84%, 77%, and 100% adequacy of images, respectively. Of the 32 inadequate images, 18 of these were incomplete focused assessment with sonography for trauma (FAST) examinations with a reading of negative for free fluid. IMPLICATIONS FOR PRACTICE: NPs are able to perform focused u/s with a high degree of accuracy, and a 16-h guideline-based course serves as a good introductory foundation. PMID- 20590957 TI - Taking charge of the challenge: factors to consider in taking your first nurse practitioner job. AB - PURPOSE: To describe factors that ensure a smooth transition from nurse practitioner (NP) student to independent NP during the first year of practice. DATA SOURCES: Two contrasting case examples, the authors' experiences, and selected professional literature. CONCLUSIONS: Key points to consider upon searching or taking a first NP job include patient, colleague, and clinic factors. Patient factors include mix of patient presentations, complexity of patient presentations, insurance status, and population. Colleague factors include mentorship, charting, mix of providers, and availability of providers. Perhaps most importantly, clinic factors include productivity expectations, practice mission, charting systems, on-call requirements, supervision of other staff, and teaching status. Together, these factors can largely determine whether an NP's days are satisfying or frustrating in a new job. IMPLICATIONS FOR PRACTICE: The transition from NP student to independent NP can be daunting. Although nursing schools and practice sites have responsibilities to ensure the transition is smooth, the new NP is ultimately responsible for the transition. PMID- 20590958 TI - The bridge: providing nursing care for survivors of sexual violence. AB - PURPOSE: To describe the experiences of nurses who provide care for survivors of sexual violence (SV) on a number of different types of hospital units. DATA SOURCES: Semi-structured interviews of 23 unit managers and 12 advanced practice nurses from four tertiary care hospitals were audiotaped and transcribed. Participants were asked to describe how they screen for SV and how they provide care for survivors. A team approach was used to conduct a thematic analysis of the data. CONCLUSIONS: The bridge metaphor was chosen as the central theme of the data because it captures three key aspects of the participants' experiences: an initial sense of disconnection from patients who are survivors of SV (being separated on opposite shores), the need to proceed cautiously (tentatively stepping onto the bridge), and the experience of forming a meaningful connection that serves as the context of care (meeting on the bridge and crossing it together). IMPLICATIONS FOR PRACTICE: This research suggests that nurses provide quality care for survivors of SV by intuitively responding to survivors' cues of distress, cautiously broaching the topic of violence, and finding ways to ease the healthcare encounter. PMID- 20590959 TI - Relationships between aggression, depression, and alcohol, tobacco: implications for healthcare providers in student health. AB - PURPOSE: To determine the prevalence of aggression, depression, and at-risk health behaviors in a random sample of undergraduate college students and to explore the relationship between these variables. DATA SOURCES: The study survey was sent to 2500 undergraduate students; 428 participated, responding to items from the National College Health Risk Behavior Survey about alcohol, drug and tobacco, violence and aggression, the Beck Depression Inventory II, and items adapted from the Overt Aggression Scale. CONCLUSIONS: Almost one third of the sample reported cigarette smoking, 22% moderate depression, 81% drink alcohol, with 58% drinking more than five drinks at least once in the last month. Reports of verbal and physical aggression were also common. Moderate depression was related to cigarette smoking, physical, and verbal aggression, but not to heavy alcohol use. An understanding of these relationships can be utilized to screen and intervene with students at risk. IMPLICATIONS FOR PRACTICE: The results call for increased screening and treatment of depression in college students, and suggest that students with aggressive behaviors are at the highest risk for depression, and should be a group to receive specific attention for screening. PMID- 20590960 TI - Pre- and posttest evaluation of a breast cancer risk assessment program for nurse practitioners. AB - PURPOSE: Numerous studies have shown that healthcare providers, including nurse practitioners (NPs) fail to provide breast cancer risk assessment (BrCRA) in primary care settings. A potential barrier to the use of BrCRA is insufficient knowledge or training of risk assessment. The purpose of this study was to analyze the outcome of a BrCRA program developed to enhance NPs' knowledge of risk assessment and use of empiric risk assessment models. DATA SOURCES: Thirty five NPs participated in a before-after (pretest-posttest design) study evaluating the effectiveness of a BrCRA education program conducted at a national NP conference. Demographics, pre/post knowledge, and course satisfaction measures were all examined as a part of this pilot study. CONCLUSION: Continuing education through the implementation of a BrCRA program significantly increased NPs knowledge in assessing breast cancer risk and the use of empiric risk assessment models. IMPLICATIONS FOR PRACTICE: Many healthcare providers, including NPs, are inadequately prepared to assess a woman's risk for breast cancer. Understanding breast cancer risk assessment is essential if NPs are to provide appropriate counseling, management, and referral strategies needed to reduce a woman's risk for developing the disease. Continuing education provides one means to enhance NP's knowledge of BrCRA. PMID- 20590961 TI - Retraction: Management of antidepressant withdrawal reactions. PMID- 20590962 TI - Managing inflammatory arthritides: Role of the nurse practitioner and physician assistant. AB - PURPOSE: To review the current management of the inflammatory arthritides, including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. This review examines the role of the nurse practitioner (NP) and physician assistant (PA) in the management of these chronic diseases. DATA SOURCES: A review of the scientific literature and current guidelines regarding the management of inflammatory arthritides. CONCLUSIONS: NPs and PAs play important roles in the interdisciplinary team involved in the treatment of patients with chronic inflammatory arthritic conditions. The management of inflammatory arthritides has evolved with the development of new treatment strategies and is focused on early intervention and minimizing progressive joint damage. NPs and PAs are ideally positioned to educate patients regarding treatment options and other important aspects of the disease process and to monitor disease activity using a number of validated instruments. IMPLICATIONS FOR PRACTICE: Through active disease management, NPs and PAs can influence their patients to make better, more informed choices regarding treatment, which may optimize patient outcomes. PMID- 20590963 TI - Patient morbidity and root coverage outcome after subepithelial connective tissue and de-epithelialized grafts: a comparative randomized-controlled clinical trial. AB - AIMS: The aim of this randomized-controlled clinical trial was to compare the patient morbidity and root coverage outcomes of a coronally advanced flap (CAF) with connective tissue (CTG) or de-epithelialized gingival (DGG) grafts. METHODS: Fifty patients with one recession each were treated. In the control group, the CTG was harvested using the trap-door approach while in the test group the CTG resulted from the de-epithelialization of a free gingival graft. RESULTS: No statistically significant differences were demonstrated between groups in patients's pain killer consumption, post-operative discomfort and bleeding. Lower stress and better ability to chew were demonstrated in the CTG group. Analgesic consumption increased with increasing height of the graft and in the case of dehiscence/necrosis of the primary flap. Pain was negatively correlated with the residual thickness of soft tissue covering the palatal bone. A statistically greater increase in buccal soft tissue thickness was observed in the DGG group. CONCLUSIONS: No differences were demonstrated in the post-operative pain and root coverage outcome in patients subjected to CAF with CTG or DGG. PMID- 20590964 TI - Sarcomatoid renal cell carcinoma presenting in the oropharynx. AB - Metastasis stemming from a distant malignancy is far less common than an oropharyngeal primary and represents only 1% of all oral neoplasms. The difficulty in diagnosing a metastasis in the oropharynx may be compounded if the lesion is poorly differentiated and bears little resemblance to the primary tumor. We present the case of synchronous metastatic renal cell carcinoma of the mandibular gingiva in a woman with sarcomatoid clear cell renal cell carcinoma. The metastatic lesion was poorly differentiated and lacked expression of the renal cell carcinoma (RCC) antigen. In contrast, PAX-8 staining was strongly positive. This case serves to highlight the diagnostic difficulty posed by poorly differentiated lesions in the oropharynx and reinforces the sensitivity of the cell lineage-specific transcription factor PAX-8 in poorly differentiated RCC. PMID- 20590966 TI - Dentin/enamel bonding. PMID- 20590967 TI - Cracked teeth: a review of the literature. AB - Although cracked teeth are a common problem for patients and dentists, there is a dearth of evidence-based guidelines on how to prevent, diagnose, and treat cracks in teeth. The purpose of this article is to review the literature to establish what evidence exists regarding the risk factors for cracked teeth and their prevention, diagnosis, and treatment. PMID- 20590968 TI - "Biological restoration": root canal and coronal reconstruction. AB - Anterior tooth fracture, as a result of traumatic injuries, frequently occurs in dentistry. Proper reconstruction of extensively damaged teeth can be achieved through the fragment reattachment procedure known as "Biological Restoration." This case report refers to the esthetics and functional recovery of extensively damaged central maxillary incisors through the preparation and adhesive cementation of "Biological Posts and Crowns" in a young patient. Both biological posts and crowns--post and dental fragment obtained through natural, extracted teeth from another individual--represent a low-cost option and alternative technique for the morphofunctional recovery of extensively damaged anterior teeth. CLINICAL SIGNIFICANCE: The biological restorations are an alternative technique for reconstruction of extensively damaged teeth that provides highly functional and esthetic outcomes. PMID- 20590969 TI - COMMENTARY. "Biological restoration": root canal and coronal reconstruction. PMID- 20590970 TI - The effect of bleaching time on dentin fracture toughness in vitro. AB - STATEMENT OF PROBLEM: A recent study reported a decrease in dentin fracture toughness after the application of peroxide bleaching products to dentin in vitro. PURPOSE: The objective of the present study was to investigate this in vitro decrease in fracture toughness further by evaluating the effect of different peroxide application times on dentin fracture toughness. MATERIALS AND METHODS: Compact test fracture toughness specimens were prepared from coronal human. These were divided into five groups (N = 12) and subjected to either bleach (10% carbamide peroxide) and/or placebo gel for a total of 336 consecutive hours (0 and 336, 84 and 252, 168 and 168, 252 and 84, 336 and 0 hours of bleach and placebo application time, respectively). The gel materials were changed every 6 hours. Fracture toughness testing was done 24 hours after the end of bleaching using tensile loading at 10 mm/min. Results were analyzed by analysis of variance and linear regression (p < 0.05). RESULTS: Dentin fracture toughness after 252 and 336 hours was significantly reduced compared to the 0- and 84-hour bleach times. An association between fracture toughness and bleach time (r(2) = 0.82) with an inverse linear regression line (K(1C) = -0.0032 [hour] + 3.386) was found. CONCLUSIONS: A significant correlation was found between bleach time and dentin fracture toughness. Dentin fracture toughness was reduced over time during the 336-hour course of in vitro bleaching. CLINICAL SIGNIFICANCE: The results suggest that it would be prudent to minimize the length of time for clinical bleaching procedures when dentin is directly exposed to bleach. PMID- 20590971 TI - COMMENTARY. The effect of bleaching time on dentin fracture toughness in vitro. PMID- 20590972 TI - Effect of prerestorative home-bleaching on microleakage of self-etch adhesives. AB - BACKGROUND: Tooth bleaching has become a routine treatment due to patients' esthetic demands. PURPOSE: The aim of this study was to evaluate how prerestorative home-bleaching affected microleakage of resin composite restorations bonded with etch-and-rinse and self-etch adhesives. MATERIALS AND METHODS: Fifty extracted human premolar teeth were used. The bleaching agent (10% carbamide peroxide) was applied to the buccal surface of each tooth for 6 hours a day for 2 weeks. The lingual surfaces of the same teeth received no application (control). The teeth were stored in artificial saliva. After 14 days, standardized Class V cavity preparations (2 mm high, 3 mm wide, and 2 mm deep) were made on the buccal and lingual surfaces with all margins in the enamel. They were randomly divided into five groups according to the adhesive systems: an etch and-rinse adhesive (Single Bond [SB]), two two-step self-etch adhesives (Adper SE Plus [ASE] and One Coat [OC]), and two one-step self-etch adhesives (Adper Easy One [EO] and G-Bond [GB]). All adhesives were applied according to the manufacturers' instructions. The preparations were then restored using the same hybrid composite (Filtek Z250) in one increment and light-cured. The teeth were thermocycled (5/55 degrees C, 1,000x) and immersed in dye, then sectioned, and dye penetration was scored. The data were analyzed using the Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: Although statistically significant differences were found between the adhesive systems in the bleached teeth, no differences were observed in the control groups (non-bleached teeth). There were significant differences between SB/GB, SB/EO, SB/OC, and GB/ASE in the bleached teeth (p < 0.05). When comparing bleached and non-bleached teeth within each adhesive system, only SB and EO produced higher leakage scores when bleaching was applied. The other groups showed no difference in terms of bleaching (p > 0.05). CONCLUSION: Prerestorative home-bleaching had an adverse effect on microleakage of SB and EO. CLINICAL SIGNIFICANCE: The effect of prerestorative home-bleaching agents on microleakage of composite resin restorations differs according to the type of adhesive material used. PMID- 20590973 TI - COMMENTARY. Effect of prerestorative home-bleaching on microleakage of self-etch adhesives. PMID- 20590974 TI - Adhesive dentistry. A full time practitioner's perspective. PMID- 20590975 TI - Critical appraisal. Options for dentin/enamel bonding: part III. AB - Four categories of resin-based dentin/enamel adhesives are currently available. These include the three-step etch-&-rinse, "one-bottle" etch-&-rinse, two-step self-etch primer systems, and "all-in-one" self-etch adhesives. In consecutive issues of the Journal, the Critical Appraisal series is presenting salient publications on research in each of the categories. The first two installments focused on the etch-&-rinse systems. The series continues with this review of papers on the two-step self-etch primer systems. PMID- 20590976 TI - International practices in the provision of teratology information: a survey of international teratogen information programmes and comparisons with the North American model. AB - RATIONALE, AIMS AND OBJECTIVES: Teratology Information Services (TIS) provide health care professionals and the public with information regarding the safety and/or risk of exposures during pregnancy and lactation, mainly via telephone consultations. An international comparison of clinical practices at TIS has never been conducted. The survey objective was to compare international TIS to North American TIS, with an aim to identify strengths and challenges that can lead to service improvement. METHODS: Twenty-two international TIS were approached for participation during an international conference. TIS were surveyed on information in six categories: services, staffing, operations, data collection, knowledge transfer activities and additional information. Data were summarized using descriptive statistics. Statistical tests were conducted using SPSS(r). RESULTS: Sixteen TIS from 12 countries participated. Survey results were compared with previously reported results from a similar survey of North American TIS (16 US, two Canadian). TIS exist in a variety of departments and settings, but most commonly are in university hospitals. Pregnant women were the most commonly counselled group worldwide. International TIS spent significantly more time fielding inquiries regarding medications, while North American TIS had a wider variety of inquiry categories. All TIS could improve budget tracking. CONCLUSIONS: Overall, service practices and goals were similar, although international TIS conducted more follow-up with service users than North American TIS. This report offers TIS the first ever opportunity to compare practices. Increased dialogue between TIS encourages sharing of best practices and improves the ability of these important public health programmes to support women and health care providers. PMID- 20590977 TI - Identification of predictive factors for neck of femur fractures in patients sustaining another recent fracture. PMID- 20590978 TI - An assessment of drug administration compliance in a university hospital centre. AB - RATIONALE, AIMS AND OBJECTIVES: Ensuring the safety of the medication process is a major world health concern. Within this framework, a field study of compliance at various stages of the medication process in health care units was conducted. The objective of our study was to compare compliance at the moment of drug administration at the patient's bedside before and after implementing certain measures (self-study activities for the nursing staff, publication of the findings of the preliminary study and identification of priorities for action, among others). METHODS: This is an observational study aimed at comparing compliance at various stages of the medication process in terms of dose verification, preparation and administration, on ward, before and after the implementation of corrective measures. Compliance was evaluated using an observational checklist that included 36 criteria. The evaluation was conducted on inpatients in nine health care units and the Emergency Care Unit of a university hospital centre. Compliance rates were calculated for each evaluated criterion separately and by category. The degree of significance and corresponding changes between 2007 and 2008 were also measured. RESULTS: The compliance rate for all the applicable criteria used on the checklist showed a significant increase from 16% in 2007 to 28% in 2008. A significant increase was also observed in the compliance rates for drug verification (91% vs. 76%) and drug preparation on wards (50% vs. 23%), particularly with regard to entering drug names and a second identifier on the label. CONCLUSIONS: Compliance rates at various separately evaluated stages in 2008 were relatively satisfactory. There is, however, room for improvement in total compliance. The introduction of simple tools and adapted communication strategies led to a sizeable improvement in the medication process at our facility. PMID- 20590979 TI - An economic evaluation of water birth: the cost-effectiveness of mother well being. AB - PURPOSE: To assess the cost-effectiveness of water compared with normal land delivery. METHODS: A retrospective controlled study was conducted over a two-year period in a Northern Italian hospital. The cohort included all the 110 women who completed a water birth and 110 women who had a land birth during the same period. The two groups were compared with respect to labour duration, perineal tear and newborn's health status. The economic evaluation adopted a cost effectiveness approach in relation to presence/absence of perineal tears. RESULTS: In the water delivery group 58 women (52.7%) experienced at least one perineal tear versus 80 (72.7%) in the traditional delivery group. The mean duration of labour was similar in the two groups. Neonatal well-being, expressed as Apgar score, did not differ significantly among the two groups at the first minute (9.48 vs. 9.28) and was slightly higher at 5 minutes in the water delivery group (9.95 vs. 9.84; P = 0.0269). Water delivery was found to be both more costly [DeltaC = ?279; 95% confidence interval (CI): 262-296] and more effective in terms of avoided perineal tears. The incremental health care cost per avoided perineal tear because of water delivery was estimated of ?1395.7 (95% CI: 1049.2 3608.5). CONCLUSION: Water birth, as compared with traditional delivery, allows for an increase in maternal well-being and is cost-effective. PMID- 20590980 TI - Thiele massage as a therapeutic option for women with chronic pelvic pain caused by tenderness of pelvic floor muscles. AB - AIMS AND OBJECTIVES: Musculoskeletal system has been found to be involved in genesis and perpetuation of chronic pelvic pain (CPP) and has strong evidences that up to 80% of women with CPP present dysfunction of the musculoskeletal system. In this study, we report a series of women with CPP caused by tenderness of pelvic floor muscles successfully treated with Thiele massage. METHODS: Were included in this study six women with CPP caused by tenderness of the levator ani muscle that underwent transvaginal massage using the Thiele technique, over a period of 5 minutes repeated once a week for 4 weeks. After 1 month, the women returned for follow-up. RESULTS: The median tenderness score for the six women evaluated was 3 at the first evaluation and 0 after 1 month of follow-up (P < 0.01). The mean Visual Analogue Scale and McGill Pain Index scores were 8.1 and 34, respectively, at the first evaluation, and 1.5 and 16.6 at follow-up (P < 0.01). CONCLUSION: Thiele massage appears to be very helpful for women with CPP caused by tenderness of the levator ani muscle. However, these results are preliminary and a larger number of women are necessary to obtain more conclusive results. PMID- 20590982 TI - Formation of the fertilization pore during oogenesis of the fern Ceratopteris thalictroides. AB - The development of the fertilization pore during oogenesis of the fern Ceratopteris thalictroides was followed using transmission electron microscopy. The newly formed egg is appressed closely to the adjacent cells. There are well developed plasmodesmata between the egg and the ventral canal cell, but none between the egg and the jacket cells of the archegonium. During maturation, a separation cavity is formed around the egg. However, a pore region persistently connects the egg and the ventral canal cell. The extra egg membrane is formed by deposition of sheets of endoplasmic reticulum (ER), but no ER is deposited on the inner surface of the pore region. Thus, a fertilization pore, covered by a layer of plasmalemma, is formed. The ventral canal cell undoubtedly participates the formation of the fertilization pore, probably by absorbing the sheets of ER beneath the pore region. The functional significance of the ventral canal cell in formation of the fertilization pore is discussed. The features of the mature egg include that abundant concentric membranes and osmiophilic vesicles occur in the cytoplasm of the mature egg. The initial, round nucleus of the egg eventually becomes cup-shaped. This investigation gives some new insights about the cells participating oogenesis in ferns. PMID- 20590983 TI - Genetic analysis of ele mutants and comparative mapping of ele1 locus in the control of organ internal asymmetry in garden pea. AB - Previous study has shown that during zygomorphic development in garden pea (Pisum sativum L.), the organ internal (IN) asymmetry of lateral and ventral petals was regulated by a genetic locus, SYMMETRIC PETAL 1 (SYP1), while the dorsoventral (DV) asymmetry was determined by two CYC-like TCP genes or the PsCYC genes, KEELED WINGS (K) and LOBED STANDARD 1 (LST1). In this study, two novel loci, ELEPHANT EAR-LIKE LEAF 1 (ELE1) and ELE2 were characterized. These mutants exhibit a similar defect of IN asymmetry as syp1 in lateral and ventral petals, but also display pleiotropic effects of enlarged organ size. Genetic analysis showed that ELE1 and ELE2 were involved in same genetic pathway and the enlarged size of petals but not compound leaves in ele2 was suppressed by introducing k and lst1, indicating that the enlargement of dorsal petal in ele2 requires the activities of K and LST1. An experimental framework of comparative genomic mapping approach was set up to map and clone LjELE1 locus in Lotus japonicus. Cloning the ELE1 gene will shed light on the underlying molecular mechanism during zygomorphic development and further provide the molecular basis for genetic improvement on legume crops. PMID- 20590984 TI - Biochemical characterization of soluble acid and alkaline invertases from shoots of etiolated pea seedlings. AB - Soluble invertase was purified from pea (Pisum sativum L.) by sequential procedures entailing ammonium sulfate precipitation, DEAE-Sepharose column, Con-A and Green 19-Sepharose affinity columns, hydroxyapatite column, ultra filtration, and Sephacryl 300 gel filtration. The purified soluble acid (SAC) and alkaline (SALK) invertases had a pH optimum of 5.3 and 7.3, respectively. The temperature optimum of two invertases was 37 degrees C. The effects of various concentrations of Tris-HCl, HgCl(2), and CuSO(4) on the activities of the two purified enzymes were examined. Tris-HCl and HgCl(2) did not affect SAC activity, whereas 10 mM Tris-HCl and 0.05 mM HgCl(2) inhibited SALK activity by about 50%. SAC and SALK were inhibited by 4.8 mM and 0.6 mM CuSO(4) by 50%, respectively. The enzymes display typical hyperbolic saturation kinetics for sucrose hydrolysis. The Kms of SAC and SALK were determined to be 1.8 and 38.6 mM, respectively. The molecular masses of SAC shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting were 22 kDa and 45 kDa. The molecular mass of SALK was 30 kDa. Iso-electric points of the SAC and SALK were estimated to be about pH 7.0 and pH 5.7, respectively. PMID- 20590985 TI - Role of Ca2+ on growth of Brassica campestris L. and B. juncea (L.) Czern & Coss under Na+ stress. AB - Root and shoot growth of Brassica campestris L. and B. juncea increased significantly (P < 0.01) with enhanced Ca(2+) treatment along with 60 mM NaCl in the root medium. The maximum fresh mass of shoot and root in B. juncea was recorded at 10 mM Ca(2+) concentration. The relative growth rate of shoot of both species reached its maximum at 8 mM of Ca(2+) concentration. Average rate of Ca(2+) intake (I(Ca)) was higher in B. juncea than B. campestris. In B. juncea, the average transport of Ca(2+) to shoot increased by 19%, 38%, 119%, 125% and 169% compared with the control. Furthermore specific utilization rate of Ca(2+) was higher in B. juncea than B. campestris. In B. campestris it increased by 9%, 32%, 41% and 59% at 4, 6, 8, and 10 mM of calcium in comparison to 2 mM Ca(2+) treatment. At 4, 6, 8 and 10 mM of Ca(2+) application, the increase in the leaf area ratio was 10, 17, 23 and 30%, respectively. In the shoot and root portions of B. campestris and B. juncea, Ca(2+) had a linear relationship with potassium and sulfur, whereas it was in antagonism with sodium ion. PMID- 20590986 TI - Hydrogen sulfide alleviates aluminum toxicity in germinating wheat seedlings. AB - Protective role of hydrogen sulfide (H(2)S) on seed germination and seedling growth was studied in wheat (Triticum) seeds subjected to aluminum (Al(3+)) stress. We show that germination and seedling growth of wheat is inhibited by high concentrations of AlCl(3). At 30 mmol/L AlCl(3) germination is reduced by about 50% and seedling growth is more dramatically inhibited by this treatment. Pre-incubation of wheat seeds in the H(2)S donor NaHS alleviates AlCl(3)-induced stress in a dose-dependant manner at an optimal concentration of 0.3 mmol/L. We verified that the role of NaHS in alleviating Al(3+) stress could be attributed to H(2)S/HS(-) by showing that the level of endogenous H(2)S increased following NaHS treatment. Furthermore, other sodium salts containing sulfur were ineffective in alleviating Al(3+) stress. NaHS pretreatment significantly increased the activities of amylases and esterases and sustained much lower levels of MDA and H(2)O(2) in germinating seeds under Al(3+) stress. Moreover, NaHS pretreatment increased the activities of guaiacol peroxidase, ascorbate peroxidase, superoxide dismutase and catalase and decreased that of lipoxygenase. NaHS pretreatment also decreased the uptake of Al(3+) in AlCl(3)-treated seed. Taken together these results suggest that H(2)S could increase antioxidant capability in wheat seeds leading to the alleviation of Al(3+) stress. PMID- 20590987 TI - Antisense-mediated depletion of tomato endoplasmic reticulum omega-3 fatty acid desaturase enhances thermal tolerance. AB - An endoplasmic reticulum-localized tomato omega-3 fatty acid desaturase gene (LeFAD3) was isolated. The antisense tomato plants were obtained under the control of the cauliflower mosaic virus 35S promoter (35S-CaMV). Northern blot analysis confirmed that the expression of LeFAD3 was inhibited in the tomato genome. Levels of 18:3 decreased and correspondingly levels of 18:2 increased in total lipids of leaves and roots. After heat stress, the fresh weight of the aerial parts of antisense transgenic plants was higher than that of the wild type (WT) plants. The membrane system ultrastructure of chloroplasts in leaf cells and all of the subcellular organelles in the root tips of transgenic plants remained more intact than those of WT. Relative electric conductivity increased less in transgenic plants than in WT. Under heat stress, the maximal photochemical efficiency of photosystem II (Fv/Fm) and the O(2) evolution rate decreased more in WT than in transgenic plants. These results suggested that the depletion of LeFAD3 increased the saturation of fatty acids and alleviated high temperature stress. PMID- 20590988 TI - Quantitative trait loci mapping for leaf length and leaf width in rice cv. IR64 derived lines. AB - The present study was conducted to identify quantitative trait loci (QTLs) for leaf size traits in IR64 introgression lines (INLs). For this purpose, selected F(2) populations derived from crosses between recurrent parent IR64 and its derived INLs, unique for leaf length and leaf width, were used to confirm QTLs. A total of eight QTLs, mapped on three chromosomes, were identified for the four leaf size traits in six F(2) populations. A QTL for leaf length, qLLnpt-1, in HKL69 was identified around simple sequence repeat (SSR) marker RM3709 on chromosome 1. Two QTLs for flag leaf length, qFLLnpt-2 and qFLLnpt-4, in HFG39 were indentified on chromosomes 2 and 4, respectively. For flag leaf width, a QTL, qFLWnpt-4, in HFG39 was identified around RM17483 on chromosome 4. While another QTL for flag leaf width, qFLWnpt-1, in HFG27 was identified around RM3252 on chromosome 1. A QTL for leaf width, qLWnpt-2, in HKL75 was identified around RM7451 on chromosome 2. For leaf width, two QTLs, qLWnpt-4a, qLWnpt-4b, in HKL48 and HKL99 were identified around RM7208 and RM6909, respectively on chromosome 4. Results from this study suggest the possibilities to use marker-assisted selection and pyramiding these QTLs to improve rice water productivity. PMID- 20590989 TI - RNA interference-based suppression of phosphoenolpyruvate carboxylase results in susceptibility of rapeseed to osmotic stress. AB - The diverse functions of phosphoenolpyruvate carboxylase (PEPCase; EC 4.1.1.31) in C(3) plants are not as well understood as in C(4) plants. To investigate the functions of PEPCase in C(3) plants, rapeseed (Brassica napus L.) PEPCase gene (referred to as BNPE15) was silenced by the RNA interference (RNAi) technique. Under normal growth conditions, no significant difference in lipid content and fatty acid composition were found between wild-type (WT) and transgenic rapeseed plants. However, when these plants were subjected to osmotic stress induced by osmoticum polyethylene glycol (PEG-6000), membrane permeability and membrane lipid peroxidization in roots and leaves of transgenic plants were higher than those of WT plants. It suggested that transgenic plants are more susceptible to osmotic stress than WT plants. Taken together, the results showed that the suppression of PEPCase by RNAi leads to susceptibility to osmotic stress in rapeseed, and PEPCase is involved in the response of C(3) plants to environmental stress. PMID- 20590990 TI - Delayed selfing in an alpine biennial Gentianopsis paludosa (Gentianaceae) in the Qinghai-Tibetan plateau. AB - Delayed selfing could provide ovules with an opportunity to be fertilized as a means of "pollination assurance" before the flowers wilt. It could, thus, be regarded as an adaptation to unpredictable pollinator environments. Within the alpine biennial Gentianopsis paludosa, the showy flowers and herkogamy at the early stage of a flower's life cycle may favor outcrossing. As the flower ages, anthers contact the central stigma due to the elongation of all filaments, resulting in autonomous selfing. Flower visitors are extremely rare in a high altitude population; and examination of the mating system indicates that G. paludosa is self-pollinated under natural conditions in this population. While at the lower altitude, the bumblebee visitation rate is relatively high but possibly unreliable. Stigma receptivity is the highest on the third day of anthesis, and decreases thereafter. Pollen viability is the highest when flowers open, and gradually decreases later. Self-pollination of G. paludosa occurs at the late stage of a flower's lifecycle when stigma receptivity and pollen viability have both decreased, suggesting delayed selfing and assurance of seed production. This delayed selfing could assure seed production under the constraints of pollinator scarcity, but ensure outcrossing when pollinators were available. Such a flexible pollination mechanism is highly adaptive in the alpine environment of the Qinghai Tibetan Plateau. PMID- 20590991 TI - Starch synthesis and programmed cell death during endosperm development in triticale (x Triticosecale Wittmack). AB - Triticale (x Triticosecale Wittmack) grains synthesize and accumulate starch as their main energy source. Starch accumulation rate and synthesis activities of ADP-glucose pyrophosphorylase, soluble starch synthases, granule-bound starch synthase and starch-branching enzyme showed similar pattern of unimodal curves during endosperm development. There was no significant difference in activity of the starch granule-bound protein isolated from total and separated starch granules at different developmental stages after anthesis in triticale. Evans Blue staining and analysis of DNA fragmentation indicated that cells of triticale endosperm undergo programmed cell death during its development. Dead cells within the endosperm were detected at 6 d post anthesis (DPA), and evidence of DNA fragmentation was first observed at 21 DPA. The period between initial detection of PCD to its rapid increase overlapped with the key stages of rapid starch accumulation during endosperm development. Cell death occurred stochastically throughout the whole endosperm, meanwhile, the activities of starch biosynthetic enzymes and the starch accumulation rate decreased in the late stages of grain filling. These results suggested that the timing and progression of PCD in triticale endosperm may interfere with starch synthesis and accumulation. PMID- 20590992 TI - Coronatine alleviates water deficiency stress on winter wheat seedlings. AB - With the aim to determine whether coronatine (COR) alleviates drought stress on wheat, two winter wheat (Triticum aestivum L.) cultivars, ChangWu134 (drought tolerant) and Shan253 (drought-sensitive) were studied under hydroponic conditions. Seedlings at the three-leaf stage were cultured in a Hoagland solution containing COR at 0.1 microM for 24 h, and then exposed to 20% polyethylene glycol 6000 (PEG-6000). Under simulated drought (SD), COR increased the dry weight of shoots and roots of the two cultivars significantly; the root/shoot ratio also increased by 30% for Shan253 and 40% for ChangWu134. Both cultivars treated with COR under SD (0.1COR+PEG) maintained significantly higher relative water content, photosynthesis, transpiration, intercellular concentration of CO(2) and stomatal conductance in leaves than those not treated with PEG. Under drought, COR significantly decreased the relative conductivity and malondialdehyde production, and the loss of 1,1-diphenyl-2-picrylhydrazyl scavenging activity in leaves was significantly alleviated in COR-treated plants. The activity of peroxidase, catalase, glutathione reductase and ascorbate peroxidase were adversely affected by drought. Leaves of plants treated with COR under drought produced less abscisic acid (ABA) than those not treated. Thus, COR might alleviate drought effects on wheat by reducing active oxygen species production, activating antioxidant enzymes and changing the ABA level. PMID- 20590993 TI - The interactions among DWARF10, auxin and cytokinin underlie lateral bud outgrowth in rice. AB - Previous studies have shown that DWARF10 (D10) is a rice ortholog of MAX4/RMS1/DAD1, encoding a carotenoid cleavage dioxygenase and functioning in strigolactones/strigolactone-derivatives (SL) biosynthesis. Here we use D10- RNA interference (RNAi) transgenic plants similar to d10 mutant in phenotypes to investigate the interactions among D10, auxin and cytokinin in regulating rice shoot branching. Auxin levels in node 1 of both decapitated D10-RNAi and wild type plants decreased significantly, showing that decapitation does reduce endogenous auxin concentration, but decapitation has no clear effects on auxin levels in node 2 of the same plants. This implies that node 1 may be the location where a possible interaction between auxin and D10 gene would be detected. D10 expression in node 1 is inhibited by decapitation, and this inhibition can be restored by exogenous auxin application, indicating that D10 may play an important role in auxin regulation of SL. The decreased expression of most OsPINs in shoot nodes of D10-RNAi plants may cause a reduced auxin transport capacity. Furthermore, effects of auxin treatment of decapitated plants on the expression of cytokinin biosynthetic genes suggest that D10 promotes cytokinin biosynthesis by reducing auxin levels. Besides, in D10-RNAi plants, decreased storage cytokinin levels in the shoot node may partly account for the increased active cytokinin contents, resulting in more tillering phenotypes. PMID- 20590994 TI - Characterization and expression analysis of Medicago truncatula ROP GTPase family during the early stage of symbiosis. AB - ROPs (Rho-related GTPases of plants) are small GTPases that are plant-specific signaling proteins. They act as molecular switches in a variety of developmental processes. In this study, seven cDNA clones coding for ROP GTPases have been isolated in Medicago truncatula, and conserved and divergent domains are identified in these predicted MtROP proteins. Phylogenetic analysis has indicated that MtROPs are distributed into groups II, III, IV but group I. MtROP genes are expressed in various tissues at different levels. A quantitative reverse transcription PCR analysis indicated that these MtROP genes have different expression profiles in the roots in response to infection with rhizobia. The expression of MtROP3, MtROP5 and MtROP6 are increased, as the expression of Nod factor or rhizobial-induced marker genes--NFP, Rip1 and Enod11; MtROP10 has showed enhanced expression at a certain post-inoculation time point. No significant changes in MtROP7 and MtROP9 expression have been detected and MtROP8 expression is dramatically decreased by about 80%-90%. Additionally, ROP promoter GUS analysis has showed that MtROP3, MtROP5 and MtROP6 have elevated expression in transgenic root hairs after rhizobial inoculation. These results might suggest a role for some ROP GTPases in the regulation of early stages during rhizobial infection in symbiosis. PMID- 20590995 TI - Senescence-inducible expression of isopentenyl transferase extends leaf life, increases drought stress resistance and alters cytokinin metabolism in cassava. AB - Cassava (Manihot esculenta Crantz) sheds its leaves during growth, especially within the tropical dry season. With the production of SAG12-IPT transgenic cassava we want to test the level of leaf retention and altered cytokinin metabolism of transgenic plants via the autoregulatory senescence inhibition system. After confirmation of transgene expression by molecular analysis and phenotype examination in greenhouse plants, two transgenic plant lines, 529-28 and 529-48, were chosen for further investigation. Detached mature leaves of 529 28 plants retained high levels of chlorophyll compared with wild-type leaves after dark-induced senescence treatment. Line 529-28 showed significant drought tolerance as indicated by stay-green capacity after drought stress treatment. Field experiments proved that leaf senescence syndrome was significantly delayed in 529-28 plants in comparison with wild-type and 529-48 plants. Physiological and agronomical characterizations of these plants also revealed that the induced expression of IPT had effects on photosynthesis, sugar allocation and nitrogen partitioning. Importantly, the 529-28 plants accumulated a high level of trans zeatin-type cytokinins particularly of corresponding storage O-glucosides to maintain cytokinin homeostasis. Our study proves the feasibility of prolonging the leaf life of woody cassava and also sheds light on the control of cytokinin homeostasis in cassava leaves. PMID- 20590996 TI - Identification of gamyb-4 and analysis of the regulatory role of GAMYB in rice anther development. AB - In higher plants, male reproductive development is a complex biological process that includes cell division and differentiation, cell to cell communication etc., while the mechanism underlying plant male reproductive development remains less understood. GAMYB encodes a gibberellins acid (GA) inducible transcription factor that is required for the early anther development in rice (Oryza sativa L.). Here, we report the isolation and characterization of a new allele gamyb-4 with a C base deletion in the second exon (+2308), causing a frame shift and premature translational termination. Histological analysis showed that gamyb-4 developed abnormal enlarged tapetum and could not undergo normal meiosis. To understand the regulatory role of GAMYB, we carried out quantitative reverse transcription polymerase chain reaction analysis and comparison of microarray data. These results revealed that the expression of TDR (TAPETUM DEGENERATION RETARDATION), a tapetal cell death regulator, was downregulated in gamyb-4 and udt1 (undeveloped tapetum1). While the GAMYB expression was not obviously changed in tdr and udt1 1, and no apparent expression fold change of UDT1 in tdr and gamyb-4, suggesting that TDR may act downstream of GAMYB and UDT1, and GAMYB and UDT1 work in parallel to regulate rice early anther development. This work is helpful in understanding the regulatory network in rice anther development. PMID- 20590997 TI - Effective isolation of retrotransposons and repetitive DNA families from the wheat genome. AB - New classes of repetitive DNA elements were effectively identified by isolating small fragments of the elements from the wheat genome. A wheat A genome library was constructed from Triticum monococcum by degenerate cleavage with EcoO109I, the recognition sites of which consisted of 5'-PuGGNCCPy-3' multi-sequences. Three novel repetitive sequences pTm6, pTm69 and pTm58 derived from the A genome were screened and tested for high copy number using a blotting approach. pTm6 showed identity with integrase domains of the barley Ty1-Copia-retrotransposon BARE-1 and pTm58 showed similarity to the barley Ty3-gypsy-like retrotransposon Romani. pTm69, however, constituted a tandem array with useful genomic specificities, but did not share any identity with known repetitive elements. This study also sought to isolate wheat D-genome-specific repetitive elements regardless of the level of methylation, by genomic subtraction. Total genomic DNA of Aegilops tauschii was cleaved into short fragments with a methylation insensitive 4 bp cutter, MboI, and then common DNA sequences between Ae. tauschii and Triticum turgidum were subtracted by annealing with excess T. turgidum genomic DNA. The D genome repetitive sequence pAt1 was isolated and used to identify an additional novel repetitive sequence family from wheat bacterial artificial chromosomes with a size range of 1 395-1 850 bp. The methods successfully led pathfinding of two unique repetitive families. PMID- 20590998 TI - Social reasoning skills in adults with Down syndrome: the role of language, executive functions and socio-emotional behaviour. AB - BACKGROUND: Although the prevalence of mental illness and behaviour problems is lower in adults with Down syndrome (DS) than in other populations with intellectual disabilities, they do present emotional and relational problems, as well as social integration difficulties. However, studies reporting on specific competences known to be central in developing appropriate social relationships (e.g. social reasoning, emotion processing, theory of mind) remain rare in the adult DS population and the mechanisms underlying these people's emotional and relational difficulties are unclear. METHOD: The present study investigated the ability to understand the appropriateness of others' social behaviour in 34 adults with DS, using the Social Resolution Task (SRT). Their results were compared with those of 34 typically developing (TD) children matched for gender and receptive vocabulary. The relationships among the SRT experimental task, cognitive competences (receptive and productive vocabulary, non-verbal reasoning, inhibition, selective attention) and a caregiver-rated measure of socio-emotional behaviour were examined in the DS group. RESULTS: The DS participants' global SRT scores did not differ from those of the controls. However, analyses of the SRT subscores revealed that the DS group identified significantly fewer inappropriate situations than the control group. Nevertheless, when they correctly identified the behaviour as inappropriate, they were as well as the controls to explain the rules underlying their responses. Regression analyses showed that receptive vocabulary and selective attention and a specific dimension of the socio emotional profile (social relating skills) constituted the best predictors of the DS adults' performance on the SRT. CONCLUSIONS: The main findings show that the DS participants demonstrate relatively good social reasoning skills in comparison with TD children matched for verbal age. However, the two groups present distinctions in their response patterns, and the influence of cognitive variables on success on the SRT also appears different. While selective attention skills are found to be significant predictors for both groups, the influence of receptive vocabulary level is much stronger in the DS group. The implications of particular cognitive and socio-emotional factors for success on the SRT in this group are considered in more detail. PMID- 20590999 TI - Editorial. PMID- 20591000 TI - Survey on violence and aggression prevention and management strategies in European renal units. AB - GOALS: This descriptive survey aims to explore strategies for the prevention and management of violence and aggression in renal units in 12 European countries. METHOD: The convenience sample consisting of dialysis, nephrological and transplantation units in European countries was used. A questionnaire, developed with the collaboration of National Associations, was used. Data were analysed using STATA software. A preliminary descriptive variable analysis was performed followed by a verification of the association between variables; values of p < 0.002 were considered statistically significant. RESULTS: A total of 436 completed questionnaires were received (participation rate: 22%). Written policies and procedures regarding violence and aggression are present in 18% of units. Educational strategies are available in less than 20% of units. Incidents are prevented by security staff (48%) or pharmacological treatment (66%). Incident reporting is mandatory for any violent and aggressive behaviour in 66% of units. There are differences between European countries. DISCUSSION AND CONCLUSION: Violence and aggression prevention and management strategies are not widely implemented throughout Europe. The dissemination of information on the prevention and management of violence and aggression is vital. PMID- 20591001 TI - Toward greener dialysis: a case study to illustrate and encourage the salvage of reject water. AB - Climate change is now considered to be a major global public health concern. However, the very provision of health care itself has a significant impact upon the environment. Action must be taken to reduce this impact. Water is a precious and finite natural resource. Vast quantities of high-grade water are required to provide haemodialysis. The reverse osmosis systems used in the purification process reject approximately two-thirds of the water presented to them. Therefore, around 250 litres of 'reject water' result from the production of the dialysate required for one treatment. This good quality reject water is lost-to drain in the vast majority of centres worldwide. Simple methodologies exist to recycle this water for alternative purposes. We describe here a case study of the only UK renal service we know to have implemented such water-saving methodologies. We outline the benefits in terms of financial and environmental savings. PMID- 20591002 TI - One unit's experiences when establishing buttonhole technique, analysis of reasons for failure of procedure: a report. AB - The buttonhole technique of access of needle insertion into a single selected site in the arteriovenous fistula has proved to be a reliable alternative to older methods due to its overall low complication rates. Although the use of blunt needles improves the technique, the success rate of cannulation with these needles is difficult to predict. We analysed the short-term outcome of 16 patients receiving in-centre haemodialysis and compared clinical relevant parameters between patients with and without buttonhole technique failure. Our dialysis unit treats about 180 patients and is located in a tertiary hospital in Sao Paulo, Brazil. The variables as discussed in the paper were the same for both groups. The incidence of technique failure was 43.7%. Patients enrolled later in the study had a better buttonhole failure-free survival rates than patients enrolled at the beginning (p < 0.05). Patients' clinical characteristics did not predict the success rate of buttonhole tunnel tracks cannulation with blunt needles. This paper also reports on our successes and failures in buttonhole technique and gives some reasons and reflections for both. PMID- 20591003 TI - The changes and difficulties experienced by patients using steroids. AB - AIM: The purpose of this study is to determine the changes and difficulties experienced by patients because of the side effects of steroids and the effects on their life styles. METHOD: This descriptive analytical study was carried out through interviews using a questionnaire for data collection. The study was conducted in Rheumatology and Nephrology Polyclinic of Hacettepe University Adult Hospital in Ankara, Turkey. There were 146 rheumatology and nephrology patients in the study. RESULTS: The findings indicated that 68.4% of patients experienced changes in body appearance, and 60.4% of these said they had difficulties. It was determined that changes in the digestive system occurred in 40.4% of the patients, and 44.1% of them had a number of difficulties. Changes occurred in the bone/muscle system of 39% of the patients, and 63.2% of them had difficulties. Psychological changes were observed in 48.6% of the patients, 63.3% of whom said they experienced difficulties. CONCLUSION: It was determined that patients using steroids had difficulties due to the side effects of the drug. PMID- 20591004 TI - Correlation of periscreen strip results and white cell count in peritoneal dialysis peritonitis. AB - INTRODUCTION: Monitoring of peritoneal dialysis (PD) peritonitis can be difficult for visually impaired patients. PeriScreen strips measure leukocyte esterase activity and this might be a useful objective test that can be performed by patients at home. METHODS: A prospective study of 138 episodes of peritonitis was undertaken. Effluent samples were analysed for white cell count (WCC) and PeriScreen score on days 3 and 5. Co-morbidity data were collated from these patients. RESULTS: Effluent WCC and PeriScreen results were found to correlate with the gold standard assessment of microbiology WCC count. A positive PeriScreen result on day 5 predicted that the episode of peritonitis would relapse after treatment with a sensitivity of 80% but with a poor specificity of 45%. Patients who cleared or relapsed their peritonitis could not be differentiated based on their burden of co-morbidity, Karnofsky scores, age, dialysis vintage or infective organism. CONCLUSION: PeriScreen strip analysis correlated with microscopic WCC of PD. However, analysis of PD effluent on day 5 of treatment is not a good test to risk stratify patients for relapsing peritonitis. PMID- 20591005 TI - Effects of teaching programme on quality of life for patients with end-stage renal disease. AB - End-stage renal disease and its treatments negatively affect quality of life. Self-care is an important approach for helping the patients deal with their problems. The aim of this study was to improve self-care and quality of life of haemodialysis patients through teaching and evaluating their quality of life. This cross-section design with pre-post assessment was conducted in the dialysis unit of Suez Canal University Hospitals, participants were 50 patients receiving maintenance haemodialysis. Data were collected using a structured interview questionnaire, and the Kidney Disease Quality of Life Scale Short Form. Statistically the results show significant improvements that were revealed in the scores of many domains of quality of life, p < 0.001, except the physical domain. Statistically significant associations were revealed between pre- and postprogramme improvement in the total quality-of-life scores. The statistically significant independent predictors of quality-of-life improvement were programme attendance, dialysis duration and marital status. PMID- 20591006 TI - CE: Continuing Education Article: MANAGEMENT OF ANAEMIA IN CHRONIC KIDNEY DISEASE. AB - SUMMARY Anaemia is an almost universal issue that develops in the later stages of chronic kidney disease (CKD) primarily due to a lack of erythropoietin (EPO) and the depressed EPO response in bone marrow. This can have a profound effect on the patient's lifestyle and quality of life. Knowledge of both the psychosocial and clinical areas of CKD is imperative for healthcare professionals so that they can be at the forefront of improvements of CKD patient care. PMID- 20591010 TI - Introduction to case reports. PMID- 20591011 TI - Case report 1: A case of failed posaconazole prophylaxis. PMID- 20591012 TI - Case report 2: Fungal infections in chronic obstructive pulmonary disease. PMID- 20591013 TI - Case report 3: Colorectal cancer patient. PMID- 20591014 TI - Case report 4: Elderly patient with concomitant conditions. PMID- 20591015 TI - Case report 5: Intensive care unit patient assessed using the Candida Score. PMID- 20591016 TI - Case report 6: Candidaemia in a high risk liver transplant recipient. PMID- 20591017 TI - Discussion of case reports. PMID- 20591018 TI - CARI supplement 2010. Foreword. PMID- 20591019 TI - The CARI guidelines. Donor-specific transfusions. PMID- 20591020 TI - The CARI guidelines. Donors at risk: proteinuria. PMID- 20591021 TI - The CARI guidelines. Donors at risk: haematuria. PMID- 20591022 TI - The CARI guidelines. Donors at risk: hypertension. PMID- 20591023 TI - The CARI guidelines. Ethical considerations. PMID- 20591024 TI - The CARI guidelines. Donors at risk: obesity. PMID- 20591025 TI - The CARI guidelines. Donors at risk: impaired glucose tolerance. PMID- 20591026 TI - The CARI guidelines. Donor renal function. PMID- 20591027 TI - The CARI guidelines. Assessment of kidney function in type 2 diabetes. PMID- 20591028 TI - The CARI guidelines. Diabetes. PMID- 20591029 TI - The CARI guidelines. Prevention and management of chronic kidney disease in type 2 diabetes. PMID- 20591030 TI - The CARI guidelines. Coronary artery, cerebrovascular and peripheral vascular disease. PMID- 20591031 TI - The CARI guidelines. Cost-effectiveness and socioeconomic implications of prevention and management of chronic kidney disease in type 2 diabetes. PMID- 20591032 TI - The CARI guidelines. Timing of referral of chronic kidney disease patients to nephrology services (adult). PMID- 20591033 TI - The CARI guidelines. Natural history and progression of atherosclerotic renal vascular stenosis. PMID- 20591034 TI - The CARI guidelines. Endovascular treatment. PMID- 20591035 TI - The CARI guidelines. Screening tests for diagnosis of renal artery stenosis. PMID- 20591036 TI - The CARI guidelines. Role of distal protection devices. PMID- 20591037 TI - The CARI guidelines. Inhibition of the renin-angiotensin system. PMID- 20591038 TI - The CARI guidelines. Peritoneal dialysis versus haemodialysis (adult). PMID- 20591039 TI - The CARI guidelines. Quality of life. PMID- 20591040 TI - The CARI guidelines. Food safety recommendations for adult kidney transplant recipients. PMID- 20591041 TI - The CARI guidelines. Nutritional management of diabetes mellitus in adult kidney transplant recipients. PMID- 20591042 TI - The CARI guidelines. Nutritional management of anaemia in adult kidney transplant recipients. PMID- 20591043 TI - The CARI guidelines. Nutritional interventions for the prevention of bone disease in kidney transplant recipients. PMID- 20591044 TI - The CARI guidelines. Nutritional management of hypophosphataemia in adult kidney transplant recipients. PMID- 20591045 TI - The CARI guidelines. Nutritional management of overweight and obesity in adult kidney transplant recipients. PMID- 20591046 TI - The CARI guidelines. Nutritional management of hypertension in adult kidney transplant recipients. PMID- 20591047 TI - The CARI guidelines. Nutritional management of dyslipidaemia in adult kidney transplant recipients. PMID- 20591048 TI - The CARI guidelines. Protein requirement in adult kidney transplant recipients. PMID- 20591049 TI - The CARI guidelines. Justification for living donor kidney transplantation. PMID- 20591050 TI - The CARI guidelines. Psychosocial care of living kidney donors. PMID- 20591051 TI - The CARI guidelines. Surgical techniques in living donor nephrectomy. PMID- 20591052 TI - The CARI guidelines. Assessment of donor kidney anatomy. PMID- 20591053 TI - The CARI guidelines. Potential child-bearing donors. PMID- 20591054 TI - Abstracts of the 12th Asian Pacific Congress of Nephrology in conjunction with 4th Asian Forum of CKD Initiative 2010 & Korea-Japan HDF Forum 2010. June 5-8 2010. COEX, Seoul, Korea. PMID- 20591055 TI - Genome-wide gene expression changes in genetically stable synthetic and natural wheat allohexaploids. AB - *The present study aims to understand regulation of gene expression in synthetic and natural wheat (Triticum aestivum) allohexaploids, that combines the AB genome of Triticum turgidum and the D genome of Aegilops tauschii; and which we have recently characterized as genetically stable. *We conducted a comprehensive genome-wide analysis of gene expression that allowed characterization of the effect of variability of the D genome progenitor, the intergenerational stability as well as the comparison with natural wheat allohexaploid. We used the Affymetrix GeneChip Wheat Genome Array, on which 55 049 transcripts are represented. *Additive expression was shown to represent the majority of expression regulation in the synthetic allohexaploids, where expression for more than c. 93% of transcripts was equal to the mid-parent value measured from a mixture of parental RNA. This leaves c. 2000 (c. 7%) transcripts, in which expression was nonadditive. No global gene expression bias or dominance towards any of the progenitor genomes was observed whereas high intergenerational stability and low effect of the D genome progenitor variability were revealed. *Our study suggests that gene expression regulation in wheat allohexaploids is established early upon allohexaploidization and highly conserved over generations, as demonstrated by the high similarity of expression with natural wheat allohexaploids. PMID- 20591056 TI - Peroxisome proliferator-activated receptor gamma 2 mutation may cause a subset of ulcerative colitis. AB - AIM: Previous studies suggest the homeostasis between acquisition of tolerance to the indigenous microflora and protective immune responses appears to be disrupted in inflammatory bowel disease (IBD). Some experimental studies indicate peroxisome proliferator-activated receptor gamma (PPARgamma) has been implicated as a regulator of intestinal inflammatory responses. In addition, the toll-like receptor (TLR)-4 can regulate expression of PPARgamma in colonic epithelial cells. We attempted to demonstrate whether the functional imbalance between TLRs and PPARgamma could lead to the onset and some polymorphisms of those genes could contribute to susceptibility to IBD. METHODS: RT-PCR analysis were performed to detect TLR4 and PPARgamma mRNA associated with those of P65 of NFkappaB, TNFalpha, MyD88, NOD2/CARD15, TLR-2,5,9, in the diseased colonic mucosa in ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 7) compared with normal controls (n = 18). Consequently, we genotyped UC (n = 29) and CD (n = 10) compared with normal controls (n = 134) for the prevalence of suspicious mutations. RESULTS: In a subset of UC patients who were revealed to carry PPARgamma Pro12Ala mutation later, impaired expression of normal PPARgamma mRNA was noted in the diseased mucosa accompanied with upregulations of MyD88 TLR-4, 5, 9, P65 and TNFalpha in mRNA levels. The prevalence of PPARgamma Pro12Ala mutation was more frequently found in UC patients compared with CD patients and normal controls (P < 0.05). CONCLUSIONS: These findings suggested that imbalances between TLRs and PPARgamma in response to luminal bacteria could lead to colonic inflammation in some UC patients. Alternative explanations will be needed for the onset of the rest of UC and CD. PMID- 20591057 TI - In memoriam: Professor Dr D. Miguel Abad Gavin. PMID- 20591059 TI - In vitro production of equine embryos: state of the art. AB - CONTENTS: In vitro embryo production is possible in the horse both clinically and for research applications. Oocytes may be collected from excised ovaries post mortem, or from either immature follicles or stimulated pre-ovulatory follicles in the live mare. In vitro maturation of immature oocytes typically yields approximately 60% mature oocytes. As standard in vitro fertilization is not yet repeatable in the horse, fertilization is performed by intracytoplasmic sperm injection. Embryo culture requires medium with high glucose, at least during blastocyst development, and rates of blastocyst development similar to those for cattle (25% to 35%) may be obtained. Pregnancy rates after transfer of in vitro produced blastocysts are similar to those for embryos recovered ex vivo. PMID- 20591060 TI - Ultrasonographic imaging in small ruminant reproduction. AB - CONTENTS: Ultrasonography is a simple, reliable and non-invasive imaging technique without secondary effects. Application of ultrasonography in veterinary practice, and specifically in small ruminants, has developed to become the most efficient diagnostic tool for managing reproduction. The objectives of current revision are to offer an overview, after a short reminder of equipment and techniques for imaging genitalia in small ruminants, of the uses and utility of ultrasonography for the evaluation of physiological and pathological conditions in males and females and for the application of assisted reproductive technologies. PMID- 20591061 TI - Advances in the diagnosis and treatment of chronic infectious and post-mating induced endometritis in the mare. AB - CONTENTS: Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post-mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response. PMID- 20591062 TI - Ascending placentitis in the mare: an update. AB - CONTENTS: Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cytokines. It must be instituted early if a pregnancy is to be saved. Treatments include antibiotics, tocolytics and immunomodulators. Prompt, aggressive treatment with antibiotics has improved foal viability in experimental models of placentitis. PMID- 20591063 TI - Techniques for the insemination of low doses of stallion sperm. AB - CONTENTS: In the last decade, there has been a significant increase in the quality and commercial use of frozen equine semen. The emergence of new reproductive technologies, coupled with the high prices for an insemination dose from some stallions, the increasing costs of import and export and the marketing policies of stallion agents or owners in the sport horse industry has stimulated the fractionation of doses for insemination. Consequently, the sperm number and the volume of an insemination dose are significantly reduced. To deliver lower doses of sperm in lower volumes compared to the standard dose, two techniques are used in clinical practice. Semen can be delivered hysteroscopically (HI) or by rectally guiding a flexible pipette to the tip of the desired uterine horn (RI). Both techniques have been described with good success and have triggered an incentive to further reduce the number of spermatozoa without having a negative effect on fertility. This article will review the expected success of both techniques in clinical settings and will highlight their advantages and disadvantages both for the mare and stallion. In addition, some of the implications of reducing sperm numbers on the industry will be discussed. From the available information, it is evident that lower sperm numbers deposited by RI or HI to deliver the inseminate can result in acceptable pregnancy rates with fresh or frozen semen in commercial settings. These methods of insemination could have major implications in the implementation and commercialization of new and emerging technologies in the equine industry. PMID- 20591064 TI - Advances in swine in vitro embryo production technologies. AB - CONTENTS: Recent advances in new technologies to produce cloned and genetically modified pigs involve manipulating oocytes and/or embryos in vitro. Although a great deal of progress has been made, the current IVM-IVF systems still result in major problems: a high rate of polyspermy; and a low development rate and low quality of blastocysts for in vitro compared with the in vivo-produced embryos. This study summarizes recent advancements in IVM-IVF-IVC porcine systems. Recent methods to select monospermic embryos are also discussed. Finally, achievements in vitrification and in somatic cell nuclear transfer are discussed. PMID- 20591065 TI - Polarized light microscopy in mammalian oocytes. AB - CONTENTS: The meiotic spindle structure plays a key role in normal chromosome alignment and segregation during meiosis. Polarized light microscopy (PLM) allows non-invasive evaluation of the meiotic spindle of metaphase oocytes from different animal species. The purpose of this article is to review the use of PLM in animal reproduction, mainly in the assessment of the meiotic spindle in oocytes. A brief overview of the methods to assess the meiotic spindle is presented as well as the principles behind the PLM. The use of PLM to evaluate oocyte quality and spindle morphology is discussed and the results on the viability of the oocytes after being exposed to PLM are presented. Several researchers showed that PLM could be successfully implemented on cryopreservation, nuclear transfer and intracytoplasmic sperm injection procedures as a tool to improve the outcome of these procedures. In addition, PLM can be used to develop studies on oocyte maturation and spindle dynamics. However, the information on the practical use of this technology in farm animals is very limited and further studies are needed to assess the importance of PLM in animal reproduction. PMID- 20591066 TI - Use of cholesterol in sperm cryopreservation: present moment and perspectives to future. AB - CONTENTS: Sperm cryosurvival rates are not optimal for most species. Therefore, new cryopreservation strategies are needed with the objective of increasing the number of surviving sperm and the quality of those sperm after thawing. Cholesterol plays important roles in many sperm functions, including effects on membrane properties. One of these effects is to stabilize membranes at low temperatures. Thus, species that produce sperm which possess high membrane cholesterol : phospholipid ratios are more resistant to cold shock than sperm with low cholesterol : phospholipid ratios. Therefore, increasing the cholesterol content of sperm membranes may be a strategy that can improve sperm quality after freeze-thawing. In this review, information is presented related to using cyclodextrins pre-loaded with cholesterol for cryopreserving sperm from different species. The topics discussed include both in vitro and in vivo assessments of sperm quality after cryopreservation, as well as how increasing sperm cholesterol content affects other sperm functions. PMID- 20591067 TI - Probes and techniques for sperm evaluation by flow cytometry. AB - CONTENTS: Flow cytometry has become an important technique in sperm evaluation and is increasingly used both for routine assessment and for research in veterinary science. We have revised the literature, describing fluorescent probes that have been used for analysing spermatozoa by flow cytometry, regarding: viability, acrosomal status, capacitation, mitochondrial status, apoptotic markers, oxidative stress markers, DNA damage, sperm counting and sperm sizing. Details and problems of some techniques are reviewed, with special attention to the occurrence of non-sperm particles in the samples ('debris'). New and promising aspects of flow cytometry, such as sperm sorting using viability markers as selection criteria, are highlighted. The relationship between flow cytometry analyses and fertility and their future improvements are considered. PMID- 20591069 TI - Active immunization with glucose-dependent insulinotropic polypeptide vaccine influences brain function and behaviour in rats. AB - Glucose-dependent insulinotropic polypeptide (GIP) is involved in the aetiology of obesity induced by overnutrition, and blocking GIP activity may be valuable to anti-obesity treatment. However, GIP and GIP receptor are closely related to various brain functions which have caused very little data to be published concerning this cerebral functionality after blocking GIP activity. Here, we showed that active vaccination of mature rats with GIP immunoconjugates [GIP keyhole limpet haemocyanin (KLH)] was associated with changes in body weight. Furthermore, we also observed significant changes in brain function and behaviour. Data indicated that GIP-KLH-immunized rats showed decreased spontaneous activity in the open field test, decreased cerebral glucose utilization assessed by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT), and increased apoptosis and proliferation of hippocampal granule cells marked by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) or proliferating cell nuclear antigen method. In conclusion, we have shown that vaccine-induced antibodies inhibited GIP activity in vivo and led to significant changes in brain function and behaviour, which underscore the need to address any potential problems GIP-targeted immunotherapy may involve in further research. PMID- 20591070 TI - Kinetics of local tissue and regional lymph node IL-2 and IFN-gamma responses in experimental oral mucosa and skin contact sensitivity in mice. AB - Using ELISA, we have quantified the levels of IL-2 and IFN-gamma in the oral mucosa, ear skin and regional and distant lymph nodes in an experimental murine model of contact sensitivity (CS), induced by the hapten oxazolone (OXA). Compared to normal conditions, the levels of IL-2 peaked early (4-6 h) after hapten exposure in the hapten-exposed tissues analysed both during the first hapten exposure (sensitization) and the second (elicitation) phase, thereafter quickly to subside. The oral mucosa displayed maximal 24-fold increase in IL-2 levels after sensitization and 39-fold increase after elicitation. Respective figures for ear skin were x27 and x35 and for regional lymph nodes x8 and x9, respectively. The distant lymph nodes displayed only minor cytokine increases at any time. IFN-gamma-levels did not increase after sensitization with OXA. An increase in IFN-gamma was seen after the second exposure, peaking at 8-24 h, thereafter quickly subsiding. The oral mucosa IFN-gamma increased x14 after elicitation, the ear skin x8 and regional lymph nodes x37. The weight of the four regional lymph nodes increased from 10 to 38 mg, and the total number of cells in these lymph nodes was increased x11, peaking 48 h after the elicitation. We conclude that in CS reactions, tissue levels of IL-2 increased in buccal mucosa, ear skin and in regional lymph nodes after hapten exposure and re-exposure, IFN gamma appeared only after re-exposure to the hapten. The increased weight of the regional lymph nodes was mainly attributed to cell proliferation. The common ectodermal origin and the similarity of the CS reactions on skin and in buccal mucosa indicate that these tissues share common immunological patterns of Th1 cell reactivity, at least in dealing with haptens like OXA. PMID- 20591071 TI - Chitinase induce the release of IL-8 in human airway epithelial cells, via Ca2+ dependent PKC and ERK pathways. AB - Chitinases are produced in significant quantities by hosts defending against infections with chitin-containing organisms. However, little is known about the immune response of exogenous chitinase in human epithelial cells. IL-8 has been suggested to have a role in the pathogenesis of the allergenic inflammation of bronchial asthma. We examined whether Streptomyces griseus (S. griseus) chitinase induced IL-8 on airway epithelium and identified the involvement of intracellular signalling pathways. H292 cells were treated with S. griseus chitinase with different concentrations and times. The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction. Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to S. griseus chitinase. Cells exposed to S. griseus chitinase showed higher level of IL-8 protein production and mRNA expression. Cells stimulated by S. griseus chitinase resulted in the activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-kB) pathways. Inhibitors of Ca(2+)-dependent PKC (Ro-31-8220, calphostin C and Go6976) significantly abolished chitinase-induced expression of IL-8. However, Ca(2+)-independent PKC inhibitor (rottlerin) did not inhibit IL-8 expression. Through ERK inhibitor (U0126) and NF-kB inhibitor (caffeine acid phenethyl ester) treatment, it was proven that ERK and NF-kB regulated chitinase-induced IL-8 expression. We concluded that S. griseus chitinase-induced IL-8 expression was regulated by the activation of Ca(2+/-)-dependent PKC, ERK and NF-kB in human airway epithelial cells. PMID- 20591072 TI - Increasing antiviral activity of surfactant protein d trimers by introducing residues from bovine serum collectins: dissociation of mannan-binding and antiviral activity. AB - Collectins contribute to host defence through interactions with glycoconjugates on pathogen surfaces. We have prepared recombinant trimeric neck and carbohydrate recognition domains (NCRD) of collectins, and we now show that the NCRD of bovine conglutinin and CL-46 (like that of CL-43) have greater intrinsic antiviral activity for influenza A virus (IAV) than the human SP-D NCRD (hSP-D-NCRD). The three serum collectins differ from SP-D by having insertions adjacent to amino acid 325 and substitution of hydrophobic residues for arginine 343. We previously showed that a three amino acid (RAK) insertion, as found in CL-43, increases antiviral activity and mannan-binding activity of the hSP-D-NCRD, while the substitution of valine at 343, as in conglutinin, more strongly increased these activities. Mannan-binding activity of collectins has been considered to predict for ability to bind to high mannose glycans on viruses or other pathogens. We now show, however, that combined mutants containing the RAK insertion and R343V or R343I substitutions have greatly increased mannan-binding ability, but lower IAV binding or inhibiting activity than mutants containing R343V or R343I substitutions only. These findings indicate differences in the recognition of glycan structures of mannan and IAV by the NCRD and emphasize the importance of the flanking sequences in determining the differing interactions of human SP-D and bovine serum collectins with mannose-rich glycoconjugates on IAV and other pathogens. Of interest, we show conservation of some monoclonal antibody-binding epitopes between bovine collectin NCRD and hSP-D, suggesting shared structural motifs. PMID- 20591073 TI - IL-10 and TGF-beta immunoregulatory cytokines rather than natural regulatory T cells are associated with the resolution phase of Vogt-Koyanagi-Harada (VKH) syndrome. AB - The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease. PMID- 20591074 TI - C7 deficiency and meningococcal infection susceptibility in two spanish families. AB - In this work, we report the genetic basis of C7 deficiency in two different Spanish families. In family 1, by using exon-specific polymerase chain reaction and sequencing, a recently described mutation was found in homozygosity in the patient; a single base change in exon 15 (C2107T) leading to a stop codon that causes truncation of the C-terminal portion of C7 (Q681X). Patient's father, mother and sister were heterozygous for this mutation. Interestingly, patient's parents were not related. In family 2, a new single base mutation in exon 2 (G90A), leading to a stop codon that causes the premature truncation of C7 (W8X), was found in the patient, mother and sister 1. Additionally, patient 2, her father and sisters, displayed a missense mutation in exon 9 (G1135C) resulting in a change of aminoacid (G357R). Although sister 1 bore the same mutations in the C7 gene that patient 2, she remains asymptomatic. Because both mutations were found in the patient and her sister, we analyse other defence mechanisms such as FcgammaR polymorphisms as well as mannose-binding lectin alleles (MBL2 gene) and MBL levels. Results showed that both siblings bore identical combinations of FcgammaR allotypes and different MBL2 alleles, exhibiting patient 2 a MBL insufficient genotype. Normal MBL levels were found in patient 1 and in two previously studied C7-deficient siblings, suggesting the involvement of other mechanisms of immunity distinct of FcgammaR variants and the MBL pathway, for the absence of meningococcal recurrent infections in certain C7-deficient individuals. PMID- 20591075 TI - Analysis of VH gene rearrangement and somatic hypermutation in Sjogren's syndrome and IgG4-related sclerosing sialadenitis. AB - IgG4-related sclerosing sialadenitis is currently considered as an autoimmune disease distinct from Sjogren's syndrome (SS) and responds extremely well to steroid therapy. To further elucidate the characteristics of IgG4-related sclerosing sialadenitis, we analysed VH fragments of IgH genes and their somatic hypermutation in SS (n = 3) and IgG4-related sclerosing sialadenitis (n = 3), using sialolithiasis (n = 3) as a non-autoimmune control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of rearranged IgH genes, at least 50 clones per case (more than 500 clones in total) were sequenced for VH fragments. Monoclonal IgH rearrangement was not detected in any cases examined. When compared with sialolithiasis, there was no VH family or VH fragment specific to SS or IgG4-related sclerosing sialadenitis. However, rates of unmutated VH fragments in SS (30%) and IgG4-related sclerosing sialadenitis (39%) were higher than that in sialolithiasis (14%) with statistical significance (P = 0.0005 and P < 0.0001, respectively). This finding suggests that some autoantibodies encoded by germline or less mutated VH genes may fail to be eliminated and could play a role in the development of SS and IgG4-related sclerosing sialadenitis. PMID- 20591076 TI - Clinical and molecular characterization of X-linked hyper-IgM syndrome patients in China. AB - X-linked Hyper-IgM syndrome (XHIM) is caused by mutations of CD154 gene also known as CD40 ligand (CD40L). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study, we investigate molecular defects involved in the XHIM in five patients and identified five distinct CD40L mutations, three of which had not been previously described. P1 harboured a novel p.L193P mutation, which abolished the expression of CD40L. P2 had a frameshift deletion in exon 3 (p.E108fsX19), which also decreased the protein expression. P3 demonstrated p.E54X change in exon 2. P4 harboured the p.Q186X change in the exon 5. P5 demonstrated p. E142X change in exon 5. Mutations in P3, P4 and P5 all led to the production of premature CD40L protein. Two of the five genetically defined patients received umbilical cord blood stem cell transplantation from unrelated donor and achieved clinical remission, and the expression of CD40L on the peripheral blood mononuclear cells restored. These mutations reflect the heterogeneity of CD40L gene, indicating the need for accurate and reliable molecular testing in patients suspected of XHIM. PMID- 20591077 TI - Early changes in frequency of peripheral blood lymphocyte subpopulations in severe traumatic brain-injured patients. AB - Infections are leading causes of increased morbidity and mortality of severe traumatic brain-injured (STBI) patients. The mechanism underlying the susceptibility to the infections is still unexplained. The purpose of the study was to investigate changes in frequency of leucocytes subpopulations in peripheral blood of patients with STBI during the course of intensive care treatment. Twenty patients with STBI were included in the study. Healthy age- and sex- volunteers served as control. Peripheral blood samples were taken from these patients at day 1, 4 and 7, and peripheral blood mononuclear cells (PBMC) were isolated. The percentage of T, B lymphocyte, NK and NKT cells as well as monocytes was analysed by simultaneous detection of surface antigens using fluorochrome-conjugated monoclonal antibodies. The two major subsets of T lymphocytes (CD3(+)CD56(-)CD4(+) and CD3(+)CD56(-)CD8(+)) and NK cells (CD3( )CD56(+dim) and CD3(-)CD56(+bright)) were also analysed by flow cytometry. Extracranial infections were presented in 55% patients with STBI. At day 4, the percentage of T lymphocytes with cytotoxic phenotype significantly diminished and their numbers restored at day 7. The frequency of NKT cells showed the identical time-dependent pattern, whereas the percentage of NK cells diminished on day 4 but did not restore after 7 days. The frequency of B lymphocytes did not change significantly during the time investigated, whereas the percentage of monocytes increased immediately after the injury and gradually diminished. The decrease in cells with cytotoxic phenotype might explain high incidence of susceptibility to infection of patients with STBI. PMID- 20591078 TI - Passive acquisition of protective antibodies reactive with Bordetella pertussis in newborns via placental transfer and breast-feeding. AB - Although acquisition of anti-pertussis antibodies by the newborn via placental transfer has been demonstrated, a subsequent recrudescence of pertussis infection is often observed, particularly in infants. The present study investigated the passive transfer of anti-pertussis IgG and IgA antibodies to term newborns and their ability to neutralize bacterial pathogenicity in an in vivo experimental model using mice intracerebrally challenged with viable Bordetella pertussis. Forty paired samples of maternal/umbilical cord sera and colostrum were obtained. Anti-pertussis antibodies were analysed by immunoenzymatic assay and by Immunoblotting. Antibody neutralizing ability was assessed through intracerebral B. pertussis challenges in mice. Anti-pertussis IgG titres were equivalent in both maternal and newborn sera (medians = 1:225 and 1:265), with a transfer rate of 118%. The colostrum samples had variable specific IgA titres (median = 1:74). The immunoblotting assays demonstrated identical recognition profiles of paired maternal and newborn serum pools but different bacterial recognition intensities by colostrum pools. In the animal model, significant differences were always observed when the serum and colostrum samples and pools were compared with the positive control (P < 0.05). Unlike samples with lower anti-pertussis titres, samples with high titres showed protective capacities above 50%. Pertussis absorbed serum and colostrum pools protected 30% of mice and purified IgG antibodies protected 65%. Both pooled and single-sample protective abilities were correlated with antibody titres (P < 0.01). Our data demonstrated the effectiveness of anti-pertussis antibodies in bacterial pathogenesis neutralization, emphasizing the importance of placental transfer and breast feeding in protecting infants against respiratory infections caused by Bordetella pertussis. PMID- 20591079 TI - The burden of visceral leishmaniasis in South Asia. PMID- 20591080 TI - Lay perceptions of kala-azar, mosquitoes and bed nets in Bihar, India. AB - OBJECTIVE: To describe the lay perception of kala-azar (KA) in an endemic area of Muzaffarpur District, Bihar, India: local names, symptoms, affected persons, perceived severity and modes of transmission, as well as perceived mosquito nuisance, modes of protection and use of bed nets. METHODS: We held 16 focus group discussions (FGD) in eight remote villages with altogether 157 participants in March 2008. Separate FGDs were held according to gender, socio-economic status (SES) and with key informants. RESULTS: Kala-azar is most commonly named pilahi. Poor people were said to be the most affected. Knowledge about symptoms was satisfactory. Fever and prolonged fever were the most stated symptoms. KA was perceived as a life-threatening disease with a heavy economic burden. Mosquito bites were perceived as the main mode of transmission but in lower socio-economic groups, non-vector-related explanations were also provided. The main modes of protection from mosquitoes mentioned were the use of fumes and bed nets. Season was the strongest factor influencing the use of bed nets and non-affordability for not owning them. CONCLUSIONS: Although the sand fly is not recognised as the vector, the relatively good awareness of disease transmission by mosquitoes and the nuisance caused by their high density might be an entry point for adopting preventive measures to protect from mosquito bite and thereby indirectly preventing from KA. Educational campaigns targeted to the poorer segments of society are needed to enhance knowledge about KA, its mode of transmission, risks of getting infected and to increase bed net use. PMID- 20591081 TI - Management of visceral leishmaniasis in rural primary health care services in Bihar, India. AB - OBJECTIVE: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent, with early diagnosis based on a rapid diagnostic test and treatment with the oral drug miltefosine as its main strategy. Several recent studies have signaled underreporting of VL cases in the region. Information on treatment outcomes is scanty. Our aim was to document VL case management by the primary health care services in India. METHODS: We took a random sample of all VL patients registered in rural primary health care (PHC) facilities of Muzaffarpur district, Bihar, India during 2008. Patients were traced at home for an interview and their records were reviewed. We recorded patient and doctor delay, treatment regimens, treatment outcomes and costs incurred by patients. RESULTS: We could review records of all 150 patients sampled and interview 139 patients or their guardian. Most patients (81%) had first presented to unqualified practitioners; median delay before reaching the appropriate primary healthcare facility was 40 days (IQR 31-59 days). Existing networks of village health workers were under-used. 48% of VL patients were treated with antimonials; 40% of those needed a second treatment course. Median direct expenditure by patients was 4000 rupees per episode (IQR 2695-5563 rupees), equivalent to almost 2 months of household income. CONCLUSION: In 2008 still critical flaws remained in VL case management in the primary health care services in Bihar: obsolete use of antimonials with high failure rates and long patient delay. To meet the target of the VL elimination, more active case detection strategies are needed, and village health worker networks could be more involved. Costs to patients remain an obstacle to early case finding. PMID- 20591082 TI - Abstracts of the XXXIst International Congress of the International Society of Blood Transfusion in joint cooperation with the 43rd Congress of the DGTI. Berlin, Germany. June 26-July 1, 2010. PMID- 20591083 TI - A comparison of web sites used to manage and present home blood pressure readings. AB - Home blood pressure (HBP) monitoring is now recommended as a routine component of blood pressure management in patients with known or suspected hypertension. Over the last few years, a large number of Web sites, commonly termed Personal Health Records, have been developed so that patients can manage and present HBP readings. The objective of this report is to describe and compare these Web sites. A list of 33 desirable Web site features, organized into 4 categories, was developed. Between June and August of 2009, a total of 60 Web sites was identified, of which 20 were free or free to try. Each of the 20 Web sites displayed HBP readings in tabular and graphical formats, most offered an option to print results in tabular (70%) and graphical (70%) form, and many (47%) could download HBP data from Microsoft HealthVault. In contrast, none of the Web sites directly linked with common electronic medical records. Overall, Web sites offered between 41% and 77% of the 33 features considered desirable. In conclusion, there is considerable variation in available features on Web sites used to manage HBP data. Information presented in this report should be useful to physicians and patients in selecting a Web site for managing and presenting HBP readings and ultimately improving blood pressure control. PMID- 20591084 TI - Predicted coronary heart disease risk reduction and dual blood pressure/cholesterol goal attainment in patients with hypertension treated in real-world clinical practice. AB - Hypertension and dyslipidemia are highly co-prevalent, but often poorly controlled, coronary heart disease (CHD) risk factors. A retrospective cohort study was conducted between January 2004 and April 2008 to compare estimated 10 year CHD risk reduction and dual blood pressure and low-density lipoprotein cholesterol goal attainment (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III]) in patients with a first prescription for amlodipine monotherapy, co prescribed amlodipine + statin, or single-pill amlodipine/atorvastatin. In total, 2739 patients were prescribed amlodipine monotherapy, 653 were co-prescribed amlodipine + statin, and 227 were prescribed single-pill amlodipine/atorvastatin. Baseline CHD risk was similar in all 3 cohorts (11.0%-12.5%). Relative CHD risk reduction was greater in those prescribed single-pill amlodipine/atorvastatin (24.5%) compared with amlodipine monotherapy (14.4%, P<.01), and co-prescribed amlodipine + statin (18.4%, P=.01). The findings were driven by greater dual goal attainment for patients prescribed single-pill amlodipine/atorvastatin (50.2%) compared with amlodipine monotherapy (31.7%, P<.05) and co-prescribed amlodipine + statin (37.5%, P<.05). PMID- 20591085 TI - Relationship between exercise heart rate recovery and circadian blood pressure pattern. AB - The aim of the present cross-sectional study was to evaluate heart rate recovery (HRR) in normotensive and hypertensive individuals with either nondipper or dipper type circadian rhythm of blood pressure. Eighty-five patients were divided into 4 groups according to the presence of hypertension and pattern of circadian blood pressure as follows: (1) normotensive/dipper, n=20; (2) normotensive/nondipper, n=21; (3) hypertensive/dipper, n=22; and (4) hypertensive/nondipper, n=22. HRR indices were calculated by subtracting first, second, and third minute heart rates from the maximal heart rate obtained during stress testing and designated as HRR1, HRR2, and HRR3. Mean HRR1 values (29.7+/ 4.0 vs 26.6+/-3.7, P=.016) were significantly higher in the normotensive/dipper group than the normotensive/nondipper group. Mean HRR1 values (28.6+/-4.0 vs 24.8+/-4.6 beats per minute, P=.007) were higher in the hypertensive/dipper group than the hypertensive/nondipper group. Spearman's correlation analyses revealed a positive correlation between degree of nighttime dipping and HRR1 (r=.600, P=.001). The correlation coefficient between degree of nighttime dipping and HRR1 was higher in the hypertensive group than the normotensive group (r=.676, P=.001 and r=.575, P=.001, respectively). Blunting of the nocturnal fall in blood pressure associates with a delayed recovery of heart rate after graded maximal exercise in both normotensive and hypertensive groups. PMID- 20591086 TI - A systematic review and meta-analysis of telmisartan versus valsartan in the management of essential hypertension. AB - This was a systematic assessment of the efficacy and safety of telmisartan and valsartan for the management of blood pressure (BP) in patients with essential hypertension. The authors reviewed randomized controlled trials (RCTs) and quasi RCTs comparing telmisartan and valsartan for the management of essential hypertension in which the participants were followed for at least 6 weeks. When a metaanalysis was possible, included studies were analyzed by Review Manager 5.0 provided by Cochrane Collaboration Group. Statistics were calculated as weight mean differences (WMDs) and relative risk with a random-effect model. A total of 6 RCTs with 3762 patients were included in this metaanalysis. When the authors combined data from all treatment categories as a group, no difference was found between telmisartan and valsartan in reduction of systolic BP and diastolic BP. In subgroup analysis, telmisartan showed a significant benefit on lowering systolic BP and diastolic BP (WMD, -2.88; 95% confidence interval [CI], -5.03 to 0.73; P<0.01; and WMD,-1.73; 95% CI, -2.47 to -0.98; P<0.01; respectively). It was found that telmisartan had a higher rate of management of clinical BP compared with valsartan (relative risk, 1.09; 95% CI, 1.00-1.19; P=0.05). No difference was found in the incidence of adverse events. Telmisartan's BP lowering capabilities were comparable to those of valsartan in monotherapy. When combined with hydrochlorothiazide, telmisartan was more effective than valsartan. Telmisartan had the same safety in the treatment of essential hypertensive patients in comparison with valsartan. PMID- 20591087 TI - Prevention of microalbuminuria in patients with type 2 diabetes: what do we know? AB - Cardiovascular and chronic kidney disease are epidemic throughout industrialized societies. Diabetes leads to premature cardiovascular disease and is regarded by many as the most common etiological factor for chronic kidney disease. Because most studies of blood-pressure lowering agents in people with diabetes and hypertension have been conducted in individuals who already have some target organ damage, it is unclear whether earlier intervention could prevent or delay the onset of renal or systemic vascular disease. In early disease there is only a low possibility of observing cardiovascular or renal events; thus intervention trials in this population must rely on disease markers such as microalbuminuria. Accordingly, the authors review the evidence to support the use of microalbuminuria as a disease marker in diabetic patients based on its strong association with renal and cardiovascular events, and discuss recent trials that examine the impact of preventing or delaying the onset of microalbuminuria. PMID- 20591088 TI - Function and structure of resistance vessels in black and white people. AB - The risk of development of hypertension is greater in black people compared to white people through mechanisms that are poorly understood. Several biological and environmental factors have been proposed. Based on the role of an increased peripheral resistance in the pathogenesis of hypertension, the authors focus in this systematic review on ethnic differences in function and mechanical properties of resistance arteries in normotensive participants. PubMed was systematically searched for papers on ethnic differences in vascular function and structure. A total of 620 papers were retrieved, of which 31 papers were included in the analysis. The available data indicate that compared to normotensive whites, normotensive black people have enhanced vascular reactivity to sympathetic stimulation, attenuated responses to vasodilators, and a relatively narrow vascular lumen diameter. Of these mechanisms, the reduced vasodilation and reduced nitric oxide bioavailability in the vascular wall seem to form the most important distinction between resistance vessel properties of black and white participants. PMID- 20591089 TI - Surgical cure of hypertension in a patient with MEN 2A syndrome and mixed dopamine, metanephrine pheochromocytoma. PMID- 20591090 TI - Angiotensin receptor blocker use may decrease the incidence and progression of Alzheimer's disease and dementia in older men but the strength of the evidence is questionable. PMID- 20591093 TI - S-allyl-mercapto-captopril: a novel compound in the treatment of Cohen-Rosenthal diabetic hypertensive rats. AB - S-allyl-mercapto-captopril (CPSSA) is a conjugate of captopril with allicin, an active principle in garlic with multiple beneficial actions on metabolic syndrome abnormalities, including weight preservation, observed by the authors in fructose induced hypertensive hyperinsulinemic rats and in Koletsky rats. The aim of the study was to examine blood pressure (BP) and glucose levels in the Cohen Rosenthal Diabetic Hypertensive (CRDH) model as well as to follow their weight preservation. CRDH rats (n=14) were fed the sugar-rich copper-free diet essential for the development of diabetes mellitus. Two months later BP and blood glucose levels were measured. CPSSA was diluted in drinking water and administered at a final dose of 53.5 mg/kg/d (n=8). Control rats (n=6) received no drug (vehicle group). In contrast to control group, CPSSA prevented progressive weight gain, without a detectable effect on food and water intake. CPSSA was effective in attenuating systolic and diastolic BP (P<0.01) as well as significantly reducing glucose levels (P<0.01). Control rats continued to gain weight, whereas the groups fed CPSSA did not. CPSSA was shown to have additional beneficial effects on improving BP and glucose level, as well as preserving weight gain. The authors conclude that the combined molecule CPSSA integrates the antihypertensive feature of both allicin and captopril, making it a potential antidiabetic and cardiovascular protective agent. PMID- 20591094 TI - Metabolic abnormalities in adult and geriatric major depression with and without comorbid dementia. AB - Metabolic abnormalities and metabolic syndrome (MetS) increasingly have been linked to depression. The authors studied examined inpatients 35 years and older with major depressive disorder (MDD) to determine the prevalence of component metabolic abnormalities and the full MetS with age, treatment, and comorbid dementia. Data analysis involved retrospective cross-sectional review from a nonprofit psychiatry inpatient service of all discharges 35 years and older with a diagnosis of MDD during a 3 year period (April 1, 2003 to March 31, 2006) (N=1718). Metabolic measures included waist circumference, lipid measurements, glucose, and hypertension diagnosis. Abnormal metabolic measures and MetS were highly prevalent in both young and old patients with MDD: one or more component was present in 87.6% of older (65-99 years old) and 79.9% of younger patients. Full MetS was present in 31.5% of older and 28.9% of younger patients (not significant, P=0.85). Metabolic abnormalities were not associated with atypical antipsychotics after controlling other variables. One-quarter (n=79, 24.9%) of older inpatients had a dementia co-diagnosis. Older patients with MDD and dementia had greater risk of elevated glucose while younger patients were more often hypertensive. Longitudinal studies are needed to determine the relationships of MDD with or without dementia with these highly prevalent abnormal metabolic measures and MetS. PMID- 20591095 TI - The association between C-reactive protein levels and insulin therapy in obese vs nonobese veterans with type 2 diabetes mellitus. AB - The authors studied the association between insulin use and C-reactive protein (CRP) levels in obese (body mass index > or = 30 kg/m(2)) and nonobese (body mass index <30 kg/m(2)) patients with type 2 diabetes at the Providence Veterans Affairs Medical Center. There were 64 nonobese participants (insulin use and average daily dose, 23.4% and 7.0+/-18.2 units at baseline and 27.1% and 9.3+/ 21.0 units at follow-up, respectively) and 106 obese participants (insulin use and daily dose, 39.6% and 28.2+/-47.3 units at baseline and 43.0% and 28.7+/-47.7 units at follow-up, respectively). Both use and daily dose of insulin were modeled with CRP levels of participants upon discharge from an intensive cardiac risk management clinic and at a 1-year follow-up visit using a linear mixed effects model for repeated measures. There was a significant direct association between log CRP and both insulin use and daily dose for nonobese participants (beta=0.3, P=.03 and beta=0.01, P=.02, respectively) but not for obese participants (P=.8 and P=.5, respectively). Due to the association between insulin therapy and CRP in nonobese patients, these results may aid clinicians in deciding on the initiation of insulin therapy for nonobese diabetic patients when noninsulin alternatives are available. PMID- 20591096 TI - A local health department's school-located vaccination clinics experience with H1N1 pandemic influenza vaccine. PMID- 20591097 TI - Examination of trends and evidence-based elements in state physical education legislation: a content analysis. AB - OBJECTIVES: To develop a comprehensive inventory of state physical education (PE) legislation, examine trends in bill introduction, and compare bill factors. METHODS: State PE legislation from January 2001 to July 2007 was identified using a legislative database. Analysis included components of evidence-based school PE from the Community Guide and other authoritative sources: minutes in PE, PE activity, teacher certification, and an environmental element, including facilities and equipment. Researchers abstracted information from each bill and a composite list was developed. RESULTS: In total, 781 bills were analyzed with 162 enacted. Of the 272 bills that contained at least 1 evidence-based element, 43 were enacted. Only 4 bills included all 4 evidence-based elements. Of these 4, 1 was enacted. Funding was mentioned in 175 of the bills introduced (37 enacted) and an evaluation component was present in 172 of the bills (49 enacted). CONCLUSIONS: Based on this analysis, we showed that PE is frequently introduced, yet the proportion of bills with evidence-based elements is low. Future research is needed to provide the types of evidence required for development of quality PE legislation. PMID- 20591098 TI - Get Fit with the Grizzlies: a community-school-home initiative to fight childhood obesity. AB - BACKGROUND: Professional sport organizations in the United States have notable celebrity status, and several teams have used this "star power" to collaborate with local school districts toward the goal of affecting children's health. Program effectiveness is unknown due to the absence of comprehensive evaluations for these initiatives. The Memphis Grizzlies, the city's National Basketball Association franchise, launched "Get Fit with the Grizzlies," a 6-week, curricular addition focusing on nutrition and physical activity for the fourth and fifth grades in Memphis City Schools (MCS). The health-infused mini-unit was delivered by physical education teachers during their classes. The purpose of this study was to evaluate the "Get Fit" program effectiveness. METHODS: Survey research was employed which measured health knowledge acquisition and health behavior change using a matched pre/posttest design in randomly chosen schools (n = 11) from all elementary schools in the MCS system (N = 110). The total number of matched pre/posttests (n = 888) equaled approximately 5% of the total fourth /fifth-grade population. McNemar's test for significance (p < .05) was applied. Odds ratios were calculated for each question. RESULTS: Analyses confirmed that there was significant health knowledge acquisition (7 of 8 questions) with odds ratios confirming moderate to strong associations. Seven out of 10 health behavior change questions significantly improved after intervention, whereas odds ratios indicated a low level of association after intervention. CONCLUSIONS: This community-school-home initiative using a professional team's celebrity platform within a certain locale is largely overlooked by school districts and should be considered as a positive strategy to confront childhood obesity. PMID- 20591099 TI - Implementing and evaluating a school-based program to improve childhood vision. AB - BACKGROUND: Approximately 20% of the American schoolchildren have a vision problem. Children from low-income urban areas have been shown to have more than twice the normal rate of vision problems. This study evaluated the effectiveness of A Vision for Success, a school-based program designed to provide eyeglasses to children in a timely manner in selected New York City public elementary schools and to encourage their regular use at school. METHODS: An intervention-control group design with 265 first- and second-grade students across 8 New York City public schools was implemented. Participating students had failed a prior mandated vision screening. Students in A Vision for Success received (1) a school based professional optometric screening, (2) provision of 2 pairs of eyeglasses (1 kept by the teacher for classroom use), and (3) teachers' encouragement of eyeglass use as prescribed in school. Mean rates of classroom eyeglass use were assessed between groups by direct observation prior to and after the optometric screening. RESULTS: Mean rates of eyeglass use for students in intervention and control groups at baseline were 22% and 19%, respectively (p > .10). At follow up, eyeglass use rose to 47% in the intervention group, whereas the control group's rate remained consistent at 19% (p < .001). Significant differences persisted for boys and girls. CONCLUSIONS: Children disproportionately affected by visual dysfunction can receive glasses in a timely manner and wear them regularly in the classroom. Even more intensive efforts will be needed for some children to help ensure that they wear glasses in school. PMID- 20591100 TI - Oral malodor and related factors in Japanese senior high school students. AB - BACKGROUND: Oral malodor (halitosis or bad breath) might be an important motivation tool for improving oral health in adolescents. There are few studies that report the epidemiology of oral malodor in high school students and the relationships with lifestyle and oral health status. This research was conducted to obtain underlying data for introducing an oral health education program which targeted prevention of oral malodor as a motivation tool for changing oral health behavior in high school students. METHODS: A questionnaire, school oral examination, and oral malodor measurement were conducted on senior high school students in a Tokyo metropolitan school in 2007. A total of 474 students (male: 219, female: 255) were used for the analysis. RESULTS: Over 42% of subjects reported that they had experienced anxiety, or were conscious of oral malodor, on at least 1 occasion. The students who had detectable oral malodor comprised 39.6% of subjects. The binary logistic regression analyses showed that whether or not subjects ate breakfast before the oral examination (p < .05), the presence of plaque (p < .01), and presence of a substantive tongue coating (p < .01) were related to the presence of detectable oral malodor. CONCLUSIONS: Cleaning the oral cavity and eating breakfast are important to prevent oral malodor in high school students. This study indicated that school health education incorporating prevention of oral malodor as a motivation tool for oral health promotion could be a valuable procedure to include in high school dental health education programs. PMID- 20591101 TI - Alcohol and drug use among gang members: experiences of adolescents who attend school. AB - BACKGROUND: Problems related to gangs have been noted in large cities and in many schools across the United States. This study examined the patterns of alcohol, drug use, and related exposures among male and female high school students who were gang members. METHODS: Analyses were based on the Youth Violence Survey, conducted in 2004, and administered to over 80% of eligible public school students in grades 7, 9, 11, and 12 (N = 4131) in a high-risk, urban school district. The self-administered survey, completed during a class period, included measures of alcohol and drug use and related exposures. Tests of associations were determined using chi-square tests and logistic regression analyses. RESULTS: In this study, 8.8% of students reported gang membership. Students who initiated alcohol use prior to age 13 (OR = 4.90; 95% CI: 3.65-6.58), who drank alcohol 3 or more times per week (OR = 9.57; 95% CI: 6.09-15.03) and who used drugs 3 or more times per week (OR = 6.51; 95% CI: 4.59-9.25) were more likely to report gang membership than students who did not report alcohol or drug use. Boys were more likely than girls to report alcohol-related fighting and drug selling. DISCUSSION: Gang members were significantly more likely than non-gang members to have initiated alcohol early, to have reported a high prevalence of alcohol use, to have engaged in alcohol-related physical fighting, peer drinking, drug use, drug selling, peer drug selling, and having seen drug deals in their neighborhood. Schools may serve as a critically important source for intervention and prevention efforts for gang members, especially those in 7th grade, who still attend school. PMID- 20591102 TI - Are adolescent girls with a physical disability at increased risk for sexual violence? AB - BACKGROUND: The purpose of this study was to investigate whether US female adolescents who self-reported having a physical disability or long-term health problem were more likely to report having been physically forced to have sexual intercourse than US female adolescents without a physical disability or long-term health problem. METHODS: Using data from the 2005 U.S. National Youth Risk Behavior Survey (YRBS), we employed logistic regression analyses to estimate the association between physical disability (and other variables) and the risk for sexual violence among US high school girls. RESULTS: Female high school students who reported a physical disability or long-term health problem were more likely to report having been physically forced to have sexual intercourse than those who did not (19.6% vs 9.4%; chi(2) = 14.51, p = .003). Results from our multivariate analysis reveal that this association remained significant (adjusted odds ratio [AOR], 1.57; 95% confidence interval [CI], 1.10-2.23) after adjusting for certain demographic characteristics, physical health problems, behavioral health risks, and violent conduct. CONCLUSIONS: Our findings suggest that adolescent girls in the United States with a physical disability or long-term health problem may be at increased risk for sexual violence. It is important that national efforts to reduce sexual violence consider how to address the unmet needs of children and adolescents with disabilities. As most adolescent girls spend the majority of their time in a school setting, it is of particular importance that school health professionals are aware of the current findings. PMID- 20591104 TI - A murine model for the study of edema induced intestinal contractile dysfunction. AB - BACKGROUND: We have published extensively regarding the effects of edema on intestinal contractile function. However, we have found the need to expand our model to mice to take advantage of the much larger arsenal of research support, especially in terms of transgenic mouse availability and development. To that end, we have developed and validated a hydrostatic intestinal edema model in mice. METHODS: Male C57 Black 6 mice were subjected to a combination of high volume crystalloid resuscitation and mesenteric venous hypertension in an effort to induce hydrostatic intestinal edema. Wet to dry ratios, myeloperoxidase activity, mucosal injury scoring, STAT-3 nuclear activation, phosphorylated STAT 3 levels, NF-kappaB nuclear activation, myosin light chain phosphorylation, intestinal contractile activity, and intestinal transit were measured to evaluate the effects of the model. KEY RESULTS: High volume crystalloid resuscitation and mesenteric venous hypertension resulted in the development of significant intestinal edema without an increase in myeloperoxidase activity or mucosal injury. Edema development was associated with increases in STAT-3 and NF-kappaB nuclear activation as well as phosphorylated STAT-3. There was a decrease in myosin light chain phosphorylation, basal and maximally stimulated intestinal contractile activity, and intestinal transit. CONCLUSION & INFERENCES: Hydrostatic edema in mice results in activation of a signal transduction profile that culminates in intestinal contractile dysfunction. This novel model allows for advanced studies into the pathogenesis of hydrostatic edema induced intestinal contractile dysfunction. PMID- 20591105 TI - Differential effects of thin and thick filament disruption on zebrafish smooth muscle regulatory proteins. AB - BACKGROUND: The smooth muscle actin binding proteins Caldesmon and Tropomyosin (Tm) promote thin filament assembly by stabilizing actin polymerization, however, whether filament assembly affects either the stability or activation of these and other smooth muscle regulatory proteins is not known. METHODS: Measurement of smooth muscle regulatory protein levels in wild type zebrafish larvae following antisense knockdown of smooth muscle actin (Acta2) and myosin heavy chain (Myh11) proteins, and in colourless mutants that lack enteric nerves. Comparison of intestinal peristalsis in wild type and colourless larvae. KEY RESULTS: Knockdown of Acta2 led to reduced levels of phospho-Caldesmon and Tm. Total Caldesmon and phospho-myosin light chain (p-Mlc) levels were unaffected. Knockdown of Myh11 had no effect on the levels of either of these proteins. Phospho-Caldesmon and p-Mlc levels were markedly reduced in colourless mutants that have intestinal motility comparable with wild type larvae. CONCLUSIONS & INFERENCES: These in vivo findings provide new information regarding the activation and stability of smooth muscle regulatory proteins in zebrafish larvae and their role in intestinal peristalsis in this model organism. PMID- 20591106 TI - A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity. AB - The systematic review presented here assessed the effects of energy restriction (ER) and exercise (EX) on fat-free mass (FFM) in overweight and obese middle-aged and older adults. PubMed was searched using the key words "weight loss or energy restriction" AND "skeletal muscle or body composition," with limitations set for "human" and "middle-aged and aged." Results from 52 studies are reported as the percentages of EX (mainly aerobic training), ER, or ER+EX groups that had a specified change in body weight and FFM, since insufficient data were available for a meta-analysis. The EX groups had modest body weight and FFM changes. Eighty one percent and 39% of the ER and ER+EX groups, respectively, lost > or = 15% of body weight as FFM. These findings suggest that exercise is an effective tool to help men and postmenopausal women aged > or = 50 years, with a BMI greater than 25 kg/m(2) preserve FFM after moderate ER-induced weight loss, which is important for combating sarcopenic obesity. PMID- 20591107 TI - Dietary patterns and the risk of colorectal cancer and adenomas. AB - The association of colorectal cancer risk with select foods has been evaluated by dietary pattern analysis. This review of the literature was conducted to thoroughly examine the available evidence for the association between dietary patterns and colorectal cancers and adenomas. A total of 32 articles based on worldwide epidemiological studies were identified. Pattern identification was achieved by exploratory data analyses (principal component, factor, and cluster analyses) in most articles, and only a few used a priori-defined scores. Dietary patterns named as healthy, prudent, fruit and vegetables, fat-reduced/diet foods, vegetable/fish/poultry, fruit/whole grain/dairy, and healthy eating index-2005, recommended food and Mediterranean diet scores were all associated with reduced risk of colorectal cancer and the risk estimates varied from 0.45 to 0.90. In contrast, diets named Western, pork-processed meat-potatoes, meat-eaters, meat and potatoes, traditional patterns, and dietary risk and life summary scores were associated with increased risk of colorectal cancer with risk estimates varying from 1.18 to 11.7. Dietary patterns for adenomas were consistent with those identified for colorectal cancer. PMID- 20591108 TI - Keloids: a new challenge for nutrition. AB - Keloids are the result of a dysfunctional scarring process that leads to excessive deposition of extracellular matrix in susceptible individuals, causing them physical, psychological, and social discomfort. Many studies have investigated various aspects of keloid physiopathology; however, the relationship between dietary components and keloids has not received much attention. The present literature review was conducted to examine the available evidence related to the relationships between nutrition/nutrients and keloids. Findings from in vitro and in vivo studies indicate possible associations exist between keloids and fatty acids, soluble fibers, and phytochemicals. However, these relationships have not been fully explored and new studies need to be carried out before any efficient diet-based therapy can be prescribed for the prevention and treatment of keloids. PMID- 20591109 TI - Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management. AB - Quercetin is a unique dietary polyphenol because it can exert biphasic dose responses on cells depending on its concentration. Cancer preventative effects of quercetin are observed at concentrations of approximately 1-40 microM and are likely mediated by quercetin's antioxidant properties. Pro-oxidant effects are present at cellular concentrations of 40-100 microM. However, at higher concentrations, many novel pathways in addition to ROS contribute to its effects. The potent bioactivity of quercetin has led to vigorous study of this compound and revealed numerous pathways that could interact synergistically to prevent or treat cancer. The effect of intake and concentration on emerging pathways and how they may interact are discussed in this review. PMID- 20591110 TI - Ready-to-use therapeutic food for prevention of childhood undernutrition. AB - Undernutrition is a major contributor to child mortality and total global disease burden. Ready-to-use therapeutic food (RUTF) is recommended by the World Health Organization for community-based management of uncomplicated forms of severe acute malnutrition. New research has evaluated the role of RUTF for the prevention of childhood undernutrition. While studies have found some benefit, similar results have been seen with supplemental food aid and controversy over the role for RUTF in prevention efforts continues. For the prevention of childhood malnutrition, the following questions remain critical: Who should receive a specific nutrition intervention? What composition and form should the intervention take? And, when should the intervention be delivered? PMID- 20591115 TI - 'Just do it!' Walter Kempner (1903-1997). PMID- 20591117 TI - Absence of regulatory IL-10 enhances innate protection against filarial parasites by a neutrophil-independent mechanism. AB - Brugia malayi causes the major tropical disease, lymphatic filariasis. Chronicity of disease is associated with generation of regulatory cells secreting IL-10 and/or TGF-beta. Previous work has shown that the rate of microfilariae (Mf) clearance from the blood is mouse strain-dependent. Here, we show that IL-10 plays an important role in preventing the clearance of Mf. Indeed, anti-IL-10 antibody treatment increases the rate of Mf clearance from the bloodstream in both rapid-Mf-clearing CBA/Ca and slow-clearing C57Bl/6 mice. In addition, IL-10( /-) mice implanted intraperitoneally with Mf-producing adult nematodes have significantly lower Mf, but not adults, in comparison with wild-type mice at 3 weeks post-implantation (p.i.). Clearance of Mf from the peritoneal cavity of IL 10(-/-) mice is associated with a dramatic infiltration of neutrophils. Furthermore, rapid-Mf-clearing CBA/Ca mice have a dramatic blood neutrophilia at 24 h p.i., whereas slow-clearing C57Bl/6 mice show no such neutrophilia. Thus, neutrophils may play a role as effector cells in microfilarial infection. We therefore treated mice with anti-granulocyte antibody to abolish neutrophil recruitment during Mf infection i.v. Although anti-granulocyte treatment severely depleted neutrophils, it did not significantly reduce the rate of B. malayi Mf clearance either during primary infection or during a challenge following antigen sensitization. PMID- 20591118 TI - Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleen. AB - Natural regulatory T cells (CD4(+) CD25(+) Foxp3(+)), natural regulatory T cells (nTreg), play an important role in the regulation of inflammatory immune responses. However, the immunosuppressive properties of nTreg may unfavourably affect the host's ability to clear certain infections. In human visceral leishmaniasis (VL), reports on the frequency and function of nTreg are not conclusive. A limitation of our own previous studies that did not indicate a major role for Foxp3(+) nTreg in VL pathogenesis was that Foxp3 was measured by mRNA expression alone, as other tools were not available at the time. We have in this study assessed CD4(+)CD25(+)Foxp3(+) cells in splenic aspirates and peripheral blood mononuclear cells (PBMC) from an extensive series of patients with VL and endemic controls (EC) by flow cytometry (FACS). The results do not show increased frequencies of Foxp3(+) cells in patient with VL pre- and post treatment, neither were they elevated when compared to PBMC of EC. We conclude that active VL is not associated with increased frequencies of peripheral Foxp3 Treg or accumulation at the site of infection. PMID- 20591119 TI - Differences in immune parameters are associated with resistance to Haemonchus contortus in Caribbean hair sheep. AB - Caribbean hair sheep are more resistant to gastrointestinal nematodes than conventional wool breeds, but mechanisms that confer resistance are not fully understood. This study compared immune effector cell populations and antibody concentrations in 12 hair and 12 wool lambs infected with the abomasal parasite Haemonchus contortus and sacrificed at 3 or 27 days post-infection (p.i.) and 14 uninfected animals of each breed. Faecal egg counts were over 2.5-fold higher (P = 0.12) and packed cell volumes approximately 8% lower (P < 0.10) in infected wool lambs. Abomasal lymph nodes were heavier in infected animals (P < 0.05) and infected hair sheep had larger lymph nodes than infected wool sheep (P < 0.05). Tissue eosinophil concentrations were likewise larger (P = 0.07) in hair compared with wool sheep at 3 days p.i. Circulating levels of IgE and IgA in uninfected lambs were higher in hair sheep (P < 0.05) and during infection, hair sheep had higher serum IgA than wool sheep at 3, 5, and 21 days p.i. (P < 0.05). Serum IgE in infected lambs did not differ between breeds, but concentrations of IgE in lymph nodes were higher (P < 0.01) at 27 days p.i. in infected hair sheep. PMID- 20591120 TI - Frequency of specific CD8+ T cells for a promiscuous epitope derived from Trypanosoma cruzi KMP-11 protein in chagasic patients. AB - The K1 peptide is a CD8(+)T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein. We have previously shown that this peptide induces IFN-gamma secretion by CD8(+)T cells. The aim of this study was to characterize the frequency of K1-specific CD8(+)T cells in chagasic patients. Nineteen HLA-A2(+)individuals were selected from 50 T. cruzi infected patients using flow cytometry and SSP-PCR assays. Twelve HLA-A*0201(+)noninfected donors were included as controls. Peripheral blood mononuclear cells were stained with HLA-A2-K1 tetramer, showing that 15 of 19 infected patients have K1-specific CD8(+)T cells (0.09-0.34% frequency) without differences in disease stages or severity. Of note, five of these responders were A*0205, A*0222, A*0226, A*0259 and A*0287 after molecular typing. Thus, a phenotypic and functional comparison of K1-specific CD8(+)T cells from non-HLA-A*0201 and HLA-A*0201(+)infected patients was performed. The results showed that both non-HLA-A*0201 and HLA A*0201(+)individuals have a predominant effector memory CD8(+)T cell phenotype (CCR7-, CD62L-). Moreover, CD8(+)T cells from non-HLA-A*0201 and HLA A*0201(+)individuals expressed IL-2, IFN-gamma and perforin without any differences. These findings support that K1 peptide is a promiscuous epitope presented by HLA-A2 supertype molecules and is highly recognized by chagasic patients. PMID- 20591121 TI - A macrophage migration inhibitory factor-like tautomerase from Teladorsagia circumcincta (Nematoda: Strongylida). AB - A macrophage migration inhibitory factor (MIF)-like molecule, Tci-MIF-1, was isolated from Teladorsagia circumcincta and subjected to detailed characterization. A cDNA representing Tci-mif-1 was isolated following its identification in third-stage larvae (L3)-enriched cDNA population. Sequencing of the cDNA indicated a 348-bp open reading frame (ORF) with the closest orthologue being a MIF derived from the human hookworm Ancylostoma ceylanicum. Messenger RNA (mRNA) representing the Tci-MIF-1 transcript was detected in eggs, L3 and adult stages of T. circumcincta. The transcript was also present, but to a lesser extent in fourth-stage larvae (L4). Detection of Tci-MIF-1 protein in T. circumcincta developmental stages reflected the transcript levels identified by reverse transcriptase-PCR. Using immunohistochemistry, the Tci-MIF-1 protein was shown to have a diffuse distribution in L3 tissue, and in L4 and adult stages, the protein was localized to the nematode gut. A recombinant version of Tci-MIF-1 was produced, and enzymic assays indicated that this recombinant protein and a somatic extract of L3 possessed dopachrome tautomerase activity as has been observed previously in other MIF-like molecules. Neither native, purified Tci-MIF nor recombinant Tci-MIF-1 dramatically influenced the in vitro migration of sheep monocytes. PMID- 20591123 TI - Inhibition of cytokine production in gastro-allergic anisakiasis and Anisakis simplex sensitization-associated chronic urticaria. PMID- 20591122 TI - Strain variation in early innate cytokine induction by Plasmodium falciparum. AB - Previous work has shown that human donors vary in the magnitude and pattern of cytokines induced when peripheral blood mononuclear cells (PBMCs) are co-cultured with Plasmodium falciparum-infected erythrocytes. Whether P. falciparum strains vary in their ability to induce cytokines has not been studied in detail and is an important question, because variation in cytokine induction could affect parasite virulence and patterns of clinical disease. We investigated the early inflammatory cytokine response to four P. falciparum laboratory strains and five field isolates. Initial studies showed that parasite strain, parasitaemia and PBMC donor all had significant effects on the magnitude of pro-inflammatory cytokine responses (IFN-gamma, GM-CSF, IL-1 beta, TNF-alpha, IL-6, P < 0.005 in all cases). However, we noticed that the most highly inducing parasite strain consistently reached schizont rupture more rapidly than the other strains. When timing of schizont rupture was taken into account, parasite strains no longer differed in their cytokine induction (P = 0.383), although donor effects remained significant (P < 0.001). These data do not support the hypothesis that P. falciparum strains vary in induction of early innate cytokine responses from PBMCs, and instead are consistent with the suggestion that conserved parasite products such as haemozoin or GPI-anchors are the parasite-derived stimuli for cytokine induction. PMID- 20591124 TI - The past defines the present. PMID- 20591125 TI - Anticipatory pleasure skills training: a new intervention to reduce anhedonia in schizophrenia. AB - PURPOSE: Anhedonia is a challenging symptom of schizophrenia and remains largely recalcitrant to current pharmacological treatments. The goal of this exploratory pilot study was to assess if a cognitive-sensory intervention could improve anticipatory pleasure. DESIGN AND METHODS: Five participants meeting the Diagnostic and Statistical Manual of Mental Disorders (4th edition, Text Revision) criteria for schizophrenia, presenting severe anhedonia and stabilized on atypical antipsychotic medication, received between 10 hours and 25 hours of training. FINDINGS: Results show that the patients improved on the anticipatory scale of the Temporal Experience of Pleasure Scale. Daily activities of the patients were also increased. PRACTICE IMPLICATIONS: These preliminary data need to be interpreted with caution given the small sample of the study, but they offer promising paths to develop new interventions to alleviate anhedonia in schizophrenia. PMID- 20591126 TI - Women with ADHD: it is an explanation, not the excuse du jour. AB - PURPOSE: To call attention to attention deficit hyperactivity disorder (ADHD) as a psychiatric disorder that can limit women's potential and overall well-being. CONCLUSION: ADHD, a legitimate neurobiological disorder that is often hidden, ignored, or misdiagnosed among women, causes them to struggle in silence. Proper interventions for women with ADHD that provide significant attention to context mitigate challenges across psychological, academic, occupational, and social domains. This should amend the diagnosis du jour concept, thereby supporting mechanisms to improve early intervention and positive outcomes. PRACTICE IMPLICATIONS: Primary care practitioners play a central role in recognition, intervention, and recovery of women with ADHD. PMID- 20591127 TI - Beliefs, suffering, and healing: a clinical practice model for families experiencing mental illness. AB - PURPOSE: Mental illness often changes families' lives and relationships forever. A Family Systems Nursing framework is proposed for working collaboratively with families. CONCLUSIONS: The Illness Beliefs Model (Wright & Bell, 2009) offers clinicians ways to target illness beliefs that may perpetuate or, alternatively, soften suffering. PRACTICE IMPLICATIONS: We have learned from families that it is often not the family member with the illness who is suffering most, but rather, other family members. The complexity of "relational suffering" challenges mental health nurses to acquire knowledge and skills to work with families to soften physical, emotional, relational, and spiritual suffering. PMID- 20591128 TI - A study of the situations, features, and coping mechanisms experienced by Irish psychiatric nurses experiencing moral distress. AB - PURPOSE: The purpose of this study was to investigate moral distress in Irish psychiatric nurses. DESIGN: A qualitative descriptive methodology was used. FINDINGS: The study confirmed the presence of moral distress and the situations that gave rise to moral distress within psychiatric nurses working in acute care settings. PRACTICE IMPLICATIONS: The findings indicate that while multidisciplinary teams appear to function well on the surface, situations that give rise to moral distress are not always acknowledged or dealt with effectively. Furthermore, unresolved moral conflict impacts upon the quality of clinical decision-making by not allowing open and transparent discussions that allow clinicians the opportunity to address their concerns adequately. PMID- 20591129 TI - Post-seclusion debriefing: a core nursing intervention. AB - PURPOSE: The purpose of this study was to investigate the frequency and type of post-seclusion debriefing provided by nurses at a psychiatric unit in Melbourne, Australia. DESIGN AND METHODS: The study employed an exploratory research design. An analysis of the seclusion register was undertaken to identify the total number of seclusions over a 1-year period. A file audit tool was developed to identify seclusion debriefing interventions documented in consumer case files. FINDINGS: Post-seclusion debriefing is not routinely performed following an episode of seclusion. PRACTICE IMPLICATIONS: A post-seclusion debriefing framework needs to be developed to support best practice in managing seclusion. PMID- 20591130 TI - Clinical supervision for the treatment of adults with severe mental illness: pertinent issues when assisting graduate nursing students. AB - PURPOSE: There is little to guide advanced practice nurses to provide supervision for graduate students conducting psychotherapy with persons with serious mental illness. This article provides concrete suggestions for clinical supervision. CONCLUSIONS: Supervision should focus on assisting students to conduct recovery based psychotherapy in terms of the therapeutic alliance, methods to provide empathy, collaborative goal setting, the management of countertransference, and the development of self-awareness. PRACTICE IMPLICATIONS: In providing clinical supervision, preceptors should assist students to become more aware of their own thoughts and feelings as well as stigmatizing beliefs in order to help clients move toward recovery. PMID- 20591131 TI - Biological perspectives psychiatric drug-drug interactions: a review. PMID- 20591132 TI - The role of F1 ATP synthase beta subunit in WSSV infection in the shrimp, Litopenaeus vannamei. AB - BACKGROUND: Knowledge of the virus-host cell interaction could inform us of the molecular pathways exploited by the virus. Studies on viral attachment proteins (VAPs) and candidate receptor proteins involved in WSSV infection, allow a better understanding of how these proteins interact in the viral life cycle. In this study, our aim was to find some host cellular membrane proteins that could bind with white spot syndrome virus (WSSV). RESULTS: Two proteins were evident by using a virus overlay protein binding assay (VOPBA) with WSSV. A protein with molecular weight 53 kDa, named BP53, was analyzed in this study, which was homologous with the F1-ATP synthase beta subunit by mass spectrometry analysis. Rapid amplification of cDNA ends (RACE) PCR was performed to identify the full length cDNA of the bp53 gene. The resulting full-length gene consisted of 1836 bp, encoding 525 amino acids with a calculated molecular mass of 55.98 kDa. The deduced amino acid sequence contained three conserved domains of the F1-ATP synthase beta subunit. BP53 was therefore designated the F1-ATP synthase beta subunit of L. vannamei. The binding of WSSV to BP53 were also confirmed by competitive ELISA binding assay and co-immunoprecipitation on magnetic beads. To investigate the function of BP53 in WSSV infection, it was mixed with WSSV before the mixture was injected intramuscularly into shrimp. The resulting mortality curves showed that recombinant (r) BP53 could attenuate WSSV infection. CONCLUSIONS: The results revealed that BP53 is involved in WSSV infection. Here is the first time showed the role of shrimp F1-ATP synthase beta subunit in WSSV infection. PMID- 20591133 TI - Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance. AB - BACKGROUND: High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. METHODS: Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days. RESULTS: Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. CONCLUSION: Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic abnormalities induced by this diet model except for HHcy. PMID- 20591134 TI - A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors. AB - BACKGROUND: Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. METHODS: We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. RESULTS: The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90%) sensitivity but relatively low (50%) specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. CONCLUSIONS: These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors. PMID- 20591135 TI - Transdifferentiation-inducing HCCR-1 oncogene. AB - BACKGROUND: Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. The differentiated state of a given cell is not irreversible. It depends on the up- and downregulation exerted by specific molecules. RESULTS: We report here that HCCR-1, previously shown to play an oncogenic role in human cancers, induces epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) in human and mouse, respectively. The stem cell factor receptor CD117/c-Kit was induced in this transdifferentiated (EMT) sarcoma tissues. This MET occurring in HCCR-1 transfected cells is reminiscent of the transdifferentiation process during nephrogenesis. Indeed, expression of HCCR-1 was observed during the embryonic development of the kidney. This suggests that HCCR-1 might be involved in the transdifferentiation process of cancer stem cell. CONCLUSIONS: Therefore, we propose that HCCR-1 may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation. PMID- 20591137 TI - German Screen for Child Anxiety Related Emotional Disorders (SCARED): Reliability, Validity, and Cross-Informant Agreement in a Clinical Sample. AB - BACKGROUND: The psychometric properties and cross-informant agreement of a German translation of the Screen for Child Anxiety Related Emotional Disorders (SCARED) were assessed in a clinical sample METHODS: 102 children and adolescents in outpatient psychotherapy and their parents filled out the SCARED and Youth Self Report/Child Behaviour Checklist (YSR/CBCL). RESULTS: The German SCARED showed good internal consistency for both parent and self-report version, and proved to be convergently and discriminantly valid when compared with YSR/CBCL scales. Cross-informant agreement was moderate with children reporting both a larger number as well as higher severity of anxiety symptoms than their parents. CONCLUSION: In conclusion, the German SCARED is a valid and reliable anxiety scale and may be used in a clinical setting. PMID- 20591136 TI - Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients. AB - BACKGROUND: Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. METHODS: We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56+ cells. RESULTS: ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56+ cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56+ cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56+ cells failed to predict PFS and response in the control group. CONCLUSIONS: CD56+ cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56+ cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy. PMID- 20591138 TI - Variability over time and correlates of cholesterol and blood pressure in systemic lupus erythematosus: a longitudinal cohort study. AB - INTRODUCTION: Total cholesterol (TC) and blood pressure (BP) are likely to take a dynamic course over time in patients with systemic lupus erythematosus (SLE). This would have important implications in terms of using single-point-in-time measurements of these variables to assess coronary artery disease (CAD) risk. The objective of this study was to describe and quantify variability over time of TC and BP among patients with SLE and to determine their correlates. METHODS: Patients in the Toronto lupus cohort who had two or more serial measurements of TC and systolic and diastolic BP (SBP and DBP) were included in the analysis. Variability over time was described in terms of the proportion of patients whose TC and BP profile fluctuated between normal and elevated (TC>5.2 mmol/L; SBP>or=140 mm Hg or DBP>or=90 mm Hg), and also in terms of within- and between patient variance quantified by using analysis of variance modeling. Generalized estimating equations (GEEs) were used to determine independent correlates of each of TC, SBP, and DBP, treated as continuous outcome variables. RESULTS: In total, 1,260 patients, comprising 26,267 measurements of each of TC, SBP, and DBP, were included. Mean+/-SD number of measurements per patient was 20.8+/-20. Mean+/-SD time interval between measurements was 5.4+/-9.7 months. Mean+/-SD time interval from the start to the end of the study was 9.3+/-8.5 years. Over time, 64.7% of patients varied between having normal and elevated cholesterol levels, whereas the status of 46.4% of patients varied between normotensive and hypertensive. By using analysis of variance (ANOVA), the within-patient percentage of total variance for each of TC, SBP, and DBP was 48.2%, 51.2%, and 63.9%, respectively. By using GEE, independent correlates of TC and BP included age, disease activity, and corticosteroids; antimalarial use was negatively correlated with TC (all P values<0.0001). CONCLUSIONS: TC and BP vary markedly over time in patients with SLE. This variability is due not only to lipid-lowering and antihypertensive medications, but also to disease- and treatment-related factors such as disease activity, corticosteroids, and antimalarials. The dynamic nature of TC and BP in SLE makes a compelling case for deriving summary measures that better capture cumulative exposure to these risk factors. PMID- 20591139 TI - Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial. AB - BACKGROUND: In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated. METHODS/DESIGN: A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue > or = 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up. DISCUSSION: The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed. TRIAL REGISTRATION: Dutch Trial Register, NTR1447. PMID- 20591140 TI - Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. AB - Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS. PMID- 20591141 TI - Comparative determination of HIV-1 co-receptor tropism by Enhanced Sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping. AB - BACKGROUND: Trofile is the prospectively validated HIV-1 tropism assay. Its use is limited by high costs, long turn-around time, and inability to test patients with very low or undetectable viremia. We aimed at assessing the efficiency of population genotypic assays based on gp120 V3-loop sequencing for the determination of tropism in plasma viral RNA and in whole-blood viral DNA. Contemporary and follow-up plasma and whole-blood samples from patients undergoing tropism testing via the enhanced sensitivity Trofile (ESTA) were collected. Clinical and clonal geno2pheno[coreceptor] (G2P) models at 10% and at optimised 5.7% false positive rate cutoff were evaluated using viral DNA and RNA samples, compared against each other and ESTA, using Cohen's kappa, phylogenetic analysis, and area under the receiver operating characteristic (AUROC). RESULTS: Both clinical and clonal G2P (with different false positive rates) showed good performances in predicting the ESTA outcome (for V3 RNA-based clinical G2P at 10% false positive rate AUROC = 0.83, sensitivity = 90%, specificity = 75%). The rate of agreement between DNA- and RNA-based clinical G2P was fair (kappa = 0.74, p < 0.0001), and DNA-based clinical G2P accurately predicted the plasma ESTA (AUROC = 0.86). Significant differences in the viral populations were detected when comparing inter/intra patient diversity of viral DNA with RNA sequences. CONCLUSIONS: Plasma HIV RNA or whole-blood HIV DNA V3-loop sequencing interpreted with clinical G2P is cheap and can be a good surrogate for ESTA. Although there may be differences among viral RNA and DNA populations in the same host, DNA based G2P may be used as an indication of viral tropism in patients with undetectable plasma viremia. PMID- 20591142 TI - Rationale and methods of the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA). AB - BACKGROUND: The EURIKA study aims to assess the status of primary prevention of cardiovascular disease (CVD) across Europe. Specifically, it will determine the degree of control of cardiovascular risk factors in current clinical practice in relation to the European guidelines on cardiovascular prevention. It will also assess physicians' knowledge and attitudes about CVD prevention as well as the barriers impeding effective risk factor management in clinical practice. METHODS/DESIGN: Cross-sectional study conducted simultaneously in 12 countries across Europe. The study has two components: firstly at the physician level, assessing eight hundred and nine primary care and specialist physicians with a daily practice in CVD prevention. A physician specific questionnaire captures information regarding physician demographics, practice settings, cardiovascular prevention beliefs and management. Secondly at the patient level, including 7641 patients aged 50 years or older, free of clinical CVD and with at least one classical risk factor, enrolled by the participating physicians. A patient specific questionnaire captures information from clinical records and patient interview regarding sociodemographic data, CVD risk factors, and current medications. Finally, each patient provides a fasting blood sample, which is sent to a central laboratory for measuring serum lipids, apolipoproteins, hemoglobin A1c, and inflammatory biomarkers. DISCUSSION: Primary prevention of CVD is an extremely important clinical issue, with preventable circulatory diseases remaining the leading cause of major disease burden. The EURIKA study will provide key information to assess effectiveness of and attitudes toward primary prevention of CVD in Europe. A transnational study creates opportunities for benchmarking good clinical practice across countries and improving outcomes. (ClinicalTrials.gov number, NCT00882336). PMID- 20591143 TI - Meeting human resources for health staffing goals by 2018: a quantitative analysis of policy options in Zambia. AB - BACKGROUND: The Ministry of Health (MOH) in Zambia is currently operating with fewer than half of the health workers required to deliver basic health services. The MOH has developed a human resources for health (HRH) strategic plan to address the crisis through improved training, hiring, and retention. However, the projected success of each strategy or combination of strategies is unclear. METHODS: We developed a model to forecast the size of the public sector health workforce in Zambia over the next ten years to identify a combination of interventions that would expand the workforce to meet staffing targets. The key forecasting variables are training enrolment, graduation rates, public sector entry rates for graduates, and attrition of workforce staff. We model, using Excel (Office, Microsoft; 2007), the effects of changes in these variables on the projected number of doctors, clinical officers, nurses and midwives in the public sector workforce in 2018. RESULTS: With no changes to current training, hiring, and attrition conditions, the total number of doctors, clinical officers, nurses, and midwives will increase from 44% to 59% of the minimum necessary staff by 2018. No combination of changes in staff retention, graduation rates, and public sector entry rates of graduates by 2010, without including training expansion, is sufficient to meet staffing targets by 2018 for any cadre except midwives. Training enrolment needs to increase by a factor of between three and thirteen for doctors, three and four for clinical officers, two and three for nurses, and one and two for midwives by 2010 to reach staffing targets by 2018. Necessary enrolment increases can be held to a minimum if the rates of retention, graduation, and public sector entry increase to 100% by 2010, but will need to increase if these rates remain at 2008 levels. CONCLUSIONS: Meeting the minimum need for health workers in Zambia this decade will require an increase in health training school enrolment. Supplemental interventions targeting attrition, graduation and public sector entry rates can help close the gap. HRH modelling can help MOH policy makers determine the relative priority and level of investment needed to expand Zambia's workforce to target staffing levels. PMID- 20591144 TI - Delineating the structural, functional and evolutionary relationships of sucrose phosphate synthase gene family II in wheat and related grasses. AB - BACKGROUND: Sucrose phosphate synthase (SPS) is an important component of the plant sucrose biosynthesis pathway. In the monocotyledonous Poaceae, five SPS genes have been identified. Here we present a detailed analysis of the wheat SPSII family in wheat. A set of homoeologue-specific primers was developed in order to permit both the detection of sequence variation, and the dissection of the individual contribution of each homoeologue to the global expression of SPSII. RESULTS: The expression in bread wheat over the course of development of various sucrose biosynthesis genes monitored on an Affymetrix array showed that the SPS genes were regulated over time and space. SPSII homoeologue-specific assays were used to show that the three homoeologues contributed differentially to the global expression of SPSII. Genetic mapping placed the set of homoeoloci on the short arms of the homoeologous group 3 chromosomes. A resequencing of the A and B genome copies allowed the detection of four haplotypes at each locus. The 3B copy includes an unspliced intron. A comparison of the sequences of the wheat SPSII orthologues present in the diploid progenitors einkorn, goatgrass and Triticum speltoides, as well as in the more distantly related species barley, rice, sorghum and purple false brome demonstrated that intronic sequence was less well conserved than exonic. Comparative sequence and phylogenetic analysis of SPSII gene showed that false purple brome was more similar to Triticeae than to rice. Wheat - rice synteny was found to be perturbed at the SPS region. CONCLUSION: The homoeologue-specific assays will be suitable to derive associations between SPS functionality and key phenotypic traits. The amplicon sequences derived from the homoeologue-specific primers are informative regarding the evolution of SPSII in a polyploid context. PMID- 20591145 TI - Does improvement management of atopic dermatitis influence the appearance of respiratory allergic diseases? A follow-up study. AB - BACKGROUND: Atopic dermatitis (AD) is often the prelude to allergic diseases. The aim of this study was 1) to evaluate if an integrated management regime could bring about a change in the evolution of the disease in comparison to the results of a previous study; 2) to determine whether the refinement of allergic investigations allowed to identify more promptly the risk factors of evolution into respiratory allergic diseases. METHODS: The study included 176 children affected by AD and previously evaluated between 1993 and 2002 at the age of 9-16 months, who underwent a telephonic interview by means of a semi-structured, pre formed questionnaire after a mean follow-up time of 8 years. According to the SCORAD, at first evaluation children had mild AD in 23% of cases, moderate in 62%, severe in 15%. RESULTS: AD disappeared in 92 cases (52%), asthma appeared in 30 (17%) and rhinoconjunctivitis in 48 (27%). The factors significantly related to the appearance of asthma were: sensitization to food allergens with sIgE > 2 KU/L (cow's milk and hen's egg; P < 0.05); to inhalant allergens with sIgE > 0.35 KU/L (P < 0.05). Logistic regression analysis showed that inhalant sensitization was positively related to the occurrence of asthma (OR = 4.219). While AD showed similar rates of disappearance to those of our previous study, the incidence of asthma was reduced, at the same follow-up time, from 29% to 15% (P = 0.002), and the incidence of rhinoconjunctivitis from 35% to 24% (P = 0.02). CONCLUSION: Comparing the results with those of the previous study, integrated management of AD does not seem to influence its natural course. Nevertheless, the decrease in the percentage of children evolving towards respiratory allergic disease stresses the importance of early diagnosis and improvement management carried out by specialist centers. The presence of allergic sensitization at one year of age might predict the development of respiratory allergy. PMID- 20591146 TI - Salmonella pyomyositis complicating sickle cell anemia: a case report. AB - INTRODUCTION: Pyomyositis is a bacterial infection of skeletal muscle and a rare complication of sickle cell anemia. It may present a difficult problem in diagnosis, leading to delay in appropriate treatment and development of complications including abscess formation and osteomyelitis. CASE PRESENTATION: We report the case of a 44-year-old Afro-Caribbean woman with homozygous sickle cell disease who presented with chest crisis and later developed pyomyositis of her hip and pelvic muscles. Salmonella agbeni was isolated from blood cultures and magnetic resonance imaging confirmed the diagnosis in this case. It is noteworthy of this case that there were no antecedent signs of gastroenteritis. Drainage was not appropriate and she was treated with intravenous antibiotics for six weeks. CONCLUSIONS: Focal Salmonella infections are uncommon in soft tissue. Pyomyositis should be considered in patients with sickle cell anemia that continue to have muscle pain and high fevers, despite initial management of their sickle cell crisis. Radiological imaging, particularly magnetic resonance imaging, is a crucial tool in establishing the diagnosis. PMID- 20591147 TI - Interaction prediction and classification of PDZ domains. AB - BACKGROUND: PDZ domain is a well-conserved, structural protein domain found in hundreds of signaling proteins that are otherwise unrelated. PDZ domains can bind to the C-terminal peptides of different proteins and act as glue, clustering different protein complexes together, targeting specific proteins and routing these proteins in signaling pathways. These domains are classified into classes I, II and III, depending on their binding partners and the nature of bonds formed. Binding specificities of PDZ domains are very crucial in order to understand the complexity of signaling pathways. It is still an open question how these domains recognize and bind their partners. RESULTS: The focus of the current study is two folds: 1) predicting to which peptides a PDZ domain will bind and 2) classification of PDZ domains, as Class I, II or I-II, given the primary sequences of the PDZ domains. Trigram and bigram amino acid frequencies are used as features in machine learning methods. Using 85 PDZ domains and 181 peptides, our model reaches high prediction accuracy (91.4%) for binary interaction prediction which outperforms previously investigated similar methods. Also, we can predict classes of PDZ domains with an accuracy of 90.7%. We propose three critical amino acid sequence motifs that could have important roles on specificity pattern of PDZ domains. CONCLUSIONS: Our model on PDZ interaction dataset shows that our approach produces encouraging results. The method can be further used as a virtual screening technique to reduce the search space for putative candidate target proteins and drug-like molecules of PDZ domains. PMID- 20591148 TI - Fibromuscular dysplasia presenting as a renal infarction: a case report. AB - INTRODUCTION: Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory disease that most commonly affects the renal and internal carotid arteries. CASE PRESENTATION: We present the case of a 44-year-old Caucasian man who was admitted with complaints of loin pain and hypertension. A computed tomography scan of the abdomen revealed a right renal infarction with a nodular aspect of the right renal artery. Subsequent renal angiography revealed a typical 'string of beads' pattern of the right renal artery with thrombus formation. Oral anticoagulation was started and the secondary hypertension was easily controlled with anti hypertensive drugs. At follow-up, our patient refused percutaneous transluminal renal angioplasty as a definitive treatment. CONCLUSIONS: Fibromuscular dysplasia is the most common cause of renovascular hypertension in patients under 50 years of age. Presentation with renal infarction is rare.In fibromuscular dysplasia, angioplasty has been proven to have, at least for some indications, an advantage over anti-hypertensive drugs. Therefore, hypertension secondary to fibromuscular dysplasia is the most common cause of curable hypertension. PMID- 20591149 TI - Use of linear mixed models for genetic evaluation of gestation length and birth weight allowing for heavy-tailed residual effects. AB - BACKGROUND: The distribution of residual effects in linear mixed models in animal breeding applications is typically assumed normal, which makes inferences vulnerable to outlier observations. In order to mute the impact of outliers, one option is to fit models with residuals having a heavy-tailed distribution. Here, a Student's-t model was considered for the distribution of the residuals with the degrees of freedom treated as unknown. Bayesian inference was used to investigate a bivariate Student's-t (BSt) model using Markov chain Monte Carlo methods in a simulation study and analysing field data for gestation length and birth weight permitted to study the practical implications of fitting heavy-tailed distributions for residuals in linear mixed models. METHODS: In the simulation study, bivariate residuals were generated using Student's-t distribution with 4 or 12 degrees of freedom, or a normal distribution. Sire models with bivariate Student's-t or normal residuals were fitted to each simulated dataset using a hierarchical Bayesian approach. For the field data, consisting of gestation length and birth weight records on 7,883 Italian Piemontese cattle, a sire maternal grandsire model including fixed effects of sex-age of dam and uncorrelated random herd-year-season effects were fitted using a hierarchical Bayesian approach. Residuals were defined to follow bivariate normal or Student's t distributions with unknown degrees of freedom. RESULTS: Posterior mean estimates of degrees of freedom parameters seemed to be accurate and unbiased in the simulation study. Estimates of sire and herd variances were similar, if not identical, across fitted models. In the field data, there was strong support based on predictive log-likelihood values for the Student's-t error model. Most of the posterior density for degrees of freedom was below 4. Posterior means of direct and maternal heritabilities for birth weight were smaller in the Student's t model than those in the normal model. Re-rankings of sires were observed between heavy-tailed and normal models. CONCLUSIONS: Reliable estimates of degrees of freedom were obtained in all simulated heavy-tailed and normal datasets. The predictive log-likelihood was able to distinguish the correct model among the models fitted to heavy-tailed datasets. There was no disadvantage of fitting a heavy-tailed model when the true model was normal. Predictive log likelihood values indicated that heavy-tailed models with low degrees of freedom values fitted gestation length and birth weight data better than a model with normally distributed residuals.Heavy-tailed and normal models resulted in different estimates of direct and maternal heritabilities, and different sire rankings. Heavy-tailed models may be more appropriate for reliable estimation of genetic parameters from field data. PMID- 20591150 TI - Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores. AB - BACKGROUND: The oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell-migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. To our knowledge, IMP3 expression has not been investigated in prostate carcinomas so far. METHODS: Immunohistochemical stainings for IMP3 were performed on tissue microarray (TMA) organized samples from 507 patients: 31 normal prostate tissues, 425 primary carcinomas and 51 prostate cancer metastases or castration-resistant prostate cancers (CRPC). IMP3 immunoreactivity was semiquantitatively scored and correlated with clinical pathologic parameters including survival. RESULTS: IMP3 is significantly stronger expressed in prostate carcinomas compared to normal prostate tissues (p < 0.0001), but did not show significant correlation with the pT-stage, the proliferation index (MIB1), preoperative serum PSA level and the margin status. Only a weak and slightly significant correlation was found with the Gleason score and IMP3 expression failed to show prognostic significance in clinico pathological correlation-analyses. CONCLUSIONS: Although IMP3 is overexpressed in a significant proportion of prostate cancer cases, which might be of importance for novel therapeutic approaches, it does not appear to possess any immediate diagnostic or prognostic value, limiting its potential as a tissue biomarker for prostate cancer. These results might be corroborated by the fact, that two independent tumor cohorts were separately reviewed. PMID- 20591151 TI - EBV, HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda. AB - BACKGROUND: B cell non Hodgkin lymphomas account for the majority of lymphomas in Uganda. The commonest is endemic Burkitt lymphoma, followed by diffuse large-B cell lymphoma (DLBCL). There has been an increase in incidence of malignant lymphoma since the onset of the HIV/AIDS pandemic. However, the possible linkages of HHV8 and EBV to the condition of impaired immunity present in AIDS are still not yet very clearly understood. OBJECTIVES: 1. To describe the prevalence of Epstein-Barr virus, Human Herpes virus 8 and Human Immunodeficiency Virus-1 in B cell non Hodgkin lymphoma biopsy specimens in Kampala, Uganda.2. To describe the histopathology of non Hodgkin lymphoma by HIV serology test result in Kampala, Uganda METHOD: Tumour biopsies specimens from 119 patients with B cell non Hodgkin lymphoma were classified according to the WHO classification. Immunohistochemistry was used for detection of HHV8 and in situ hybridization with Epstein Barr virus encoded RNA (EBER) for EBV. Real time and nested PCR were used for the detection of HIV.The patients from whom the 1991-2000 NHL biopsies had been taken did not have HIV serology results therefore 145 patients biopsies where serology results were available were used to describe the association of HIV with non Hodgkin lymphoma type during 2008-2009. RESULTS: In this study, the majority (92%) of the Burkitt lymphomas and only 34.8% of the diffuse large B cell lymphomas were EBV positive. None of the precursor B lymphoblastic lymphomas or the mantle cell lymphomas showed EBV integration in the lymphoma cells.None of the Burkitt lymphoma biopsies had HIV by PCR. Of the 121 non Hodgkin B cell lymphoma patients with HIV test results, 19% had HIV. However, only 1(0.04%) case of Burkitt lymphoma had HIV. All the tumours were HHV8 negative. CONCLUSIONS: The majority of the Burkitt lymphomas and two fifths of the diffuse large B cell lymphomas had EBV. All the tumours were HHV8 negative. Generally, the relationship of NHL and HIV was weaker than what has been reported from the developed countries. We discuss the role of these viruses in lymphomagenesis in light of current knowledge. PMID- 20591152 TI - Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer. AB - BACKGROUND: Wnt factors control cell differentiation through semi-independent molecular cascades known as the beta-catenin-dependent (canonical) and independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood. RESULTS: Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic. CONCLUSIONS: Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour. PMID- 20591153 TI - RNA silencing in plants: Flash report! AB - Earlier this year plant scientists met in Santa Fe, New Mexico at the Keystone Symposium "RNA Silencing Mechanisms in Plants". Sessions included small RNA biogenesis and signalling, development and stress responses, small RNA-directed DNA methylation, and interaction with pathogens. This report highlights some of the prominent and recurring themes at the meeting and emerging arenas of future research. PMID- 20591154 TI - Dissemination of multidrug resistant Acinetobacter baumannii in various hospitals of Antananarivo Madagascar. AB - This study reports the dissemination of multidrug-resistant (MDR) OXA-23 producing Acinetobacter baumannii clones in hospitals in Antananarivo, Madagascar. A total of 53 carbapenem-resistant A. baumannii isolates were obtained from September 2006 to March 2009 in five hospitals. These resistant strains represent 44% of all A. baumannii isolates. The double disk synergy test was performed to screen for production of metallo-beta-lactamases. Polymerase chain reaction (PCR) and DNA sequencing were performed for the detection of bla(AmpC), bla(OXA-51),bla(OXA-23), bla(OXA-24), bla(IMP), bla(VIM). The presence of the insertion sequence ISAba1 relative to blaOXA-23 and blaOXA-51 was assessed by PCR. Isolates were typed by Rep-PCR. All the isolates were MDR and produced the OXA-23 carbapenemase, which was confirmed by sequencing. PCR analysis for AmpC and OXA-51 gave positive results for all strains studied. No isolates produced metallo-beta-lactamases. In all isolates ISAba1 laid upstream of blaOXA 23. The A. baumannii isolates were separated into two genotypes; genotype A had a higher prevalence (41 strains) than genotype B (12 strains). Genotype A was present in four hospitals, whilst genotype B had spread in two hospitals. The high frequency of MDR OXA-23-producing A. baumannii in various hospitals in Antananarivo is curious since carbapenems are not available in Madagascar, but it emphasises the need for infection control procedures and strict adherence to them to prevent the spread of these resistant organisms in Antananarivo and also the need to control the use of carbapenems in the future. PMID- 20591155 TI - Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene. AB - BACKGROUND: The unique property of some avian H10 viruses, particularly the ability to cause severe disease in mink without prior adaptation, enabled our study. Coupled with previous experimental data and genetic characterization here we tried to investigate the possible influence of different genes on the virulence of these H10 avian influenza viruses in mink. RESULTS: Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink. In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink. CONCLUSIONS: Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses. PMID- 20591156 TI - Comprehensive survey of human brain microRNA by deep sequencing. AB - BACKGROUND: MicroRNA (miRNA) play an important role in gene expression regulation. At present, the number of annotated miRNA continues to grow rapidly, in part due to advances of high-throughput sequencing techniques. Here, we use deep sequencing to characterize a population of small RNA expressed in human and rhesus macaques brain cortex. RESULTS: Based on a total of more than 150 million sequence reads we identify 197 putative novel miRNA, in humans and rhesus macaques, that are highly conserved among mammals. These putative miRNA have significant excess of conserved target sites in genes' 3'UTRs, supporting their functional role in gene regulation. Additionally, in humans and rhesus macaques respectively, we identify 41 and 22 conserved putative miRNA originating from non coding RNA (ncRNA) transcripts. While some of these molecules might function as conventional miRNA, others might be harmful and result in target avoidance. CONCLUSIONS: Here, we further extend the repertoire of conserved human and rhesus macaque miRNA. Even though our study is based on a single tissue, the coverage depth of our study allows identification of functional miRNA present in brain tissue at background expression levels. Therefore, our study might cover large proportion of the yet unannotated conserved miRNA present in the human genome. PMID- 20591157 TI - Oral involvement in a case of AA amyloidosis: a case report. AB - INTRODUCTION: Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein causes systemic amyloidosis, a serious inflammatory disorder. We document a male patient who developed reactive amyloidosis (AA type), most likely secondary to his long standing periodontitis. CASE PRESENTATION: A 67-year-old Turkish man complained of pain in his oral cavity (burning mouth) especially on the tongue, and had difficulty chewing and swallowing foods. A careful dental/periodontal examination was performed, including assessment of plaque, gingival condition and periodontal probing depths on all his remaining teeth. Prosthetic rehabilitation was provided three months after the completion of his periodontal and surgical therapy. The concentration of serum inflammatory markers including erythrocyte sedimentation rate, white blood cell count, fibrinogen and high sensitive C-reactive protein were measured at baseline, at the second and sixth weeks, and at three and six months after the periodontal and surgical therapy. CONCLUSIONS: Oral examination revealed a few papules on the dorsum of the tongue with two slightly painful, small ulcers, localized on the vestibule of the mouth. The mean probing depth was 9.10 +/- 0.84 mm. Biopsies of the tongue, buccal mucosa and retromolar trigone were performed and amyloid deposits were found. The serum inflammatory markers improved more dramatically at the second week of periodontal therapy than any other time intervals.Amyloidosis may manifest as periodontal destruction that leads to severe chronic periodontitis. Proper periodontal treatment may alleviate systemic inflammatory mediators caused by the amyloidosis. PMID- 20591158 TI - Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions. AB - BACKGROUND: Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human cancer gene in JAR cells. METHODS: We screened 10 different 15 mer PNAs targeting intron2 at both the 5' - and the 3'-splice site for their effects on the splicing of mdm2 using RT-PCR analysis. We also tested a PNA (2512) targeting the 3'-splice site of intron3 with a complementarity of 4 bases to intron3 and 11 bases to exon4 for its splicing modulation effect. This PNA2512 was further tested for the effects on the mdm2 protein level as well as for inhibition of cell growth in combination with the DNA damaging agent camptothecin (CPT). RESULTS: We show that several of these PNAs effectively inhibit the splicing thereby producing a larger mRNA still containing intron2, while skipping of exon3 was not observed by any of these PNAs. The most effective PNA (PNA2406) targeting the 3'-splice site of intron2 had a complementarity of 4 bases to intron2 and 11 bases to exon3. PNA (2512) targeting the 3'-splice site of intron3 induced both splicing inhibition (intron3 skipping) and skipping of exon4. Furthermore, treatment of JAR cells with this PNA resulted in a reduction in the level of MDM2 protein and a concomitant increase in the level of tumor suppressor p53. In addition, a combination of this PNA with CPT inhibited cell growth more than CPT alone. CONCLUSION: We have identified several PNAs targeting the 5'- or 3'-splice sites in intron2 or the 3' splice site of intron3 of mdm2 pre-mRNA which can inhibit splicing. Antisense targeting of splice junctions of mdm2 pre-mRNA may be a powerful method to evaluate the cellular function of MDM2 splice variants as well as a promising approach for discovery of mdm2 targeted anticancer drugs. PMID- 20591159 TI - Learning styles of medical students, general surgery residents, and general surgeons: implications for surgical education. AB - BACKGROUND: Surgical education is evolving under the dual pressures of an enlarging body of knowledge required during residency and mounting work-hour restrictions. Changes in surgical residency training need to be based on available educational models and research to ensure successful training of surgeons. Experiential learning theory, developed by David Kolb, demonstrates the importance of individual learning styles in improving learning. This study helps elucidate the way in which medical students, surgical residents, and surgical faculty learn. METHODS: The Kolb Learning Style Inventory, which divides individual learning styles into Accommodating, Diverging, Converging, and Assimilating categories, was administered to the second year undergraduate medical students, general surgery resident body, and general surgery faculty at the University of Alberta. RESULTS: A total of 241 faculty, residents, and students were surveyed with an overall response rate of 73%. The predominant learning style of the medical students was assimilating and this was statistically significant (p < 0.03) from the converging learning style found in the residents and faculty. The predominant learning styles of the residents and faculty were convergent and accommodative, with no statistically significant differences between the residents and the faculty. CONCLUSIONS: We conclude that medical students have a significantly different learning style from general surgical trainees and general surgeons. This has important implications in the education of general surgery residents. PMID- 20591160 TI - Dosimetric precision of an ion beam tracking system. AB - BACKGROUND: Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams. METHODS: A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion. Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system. RESULTS: All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements. CONCLUSIONS: The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems. PMID- 20591161 TI - Towards interoperable and reproducible QSAR analyses: Exchange of datasets. AB - BACKGROUND: QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and re-use of data. RESULTS: We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML) which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. CONCLUSIONS: Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join, extend, combine datasets and hence work collectively, but also allows for analyzing the effect descriptors have on the statistical model's performance. The presented Bioclipse plugins equip scientists with graphical tools that make QSAR ML easily accessible for the community. PMID- 20591162 TI - Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report. AB - INTRODUCTION: Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. CASE PRESENTATION: We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. CONCLUSIONS: It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm. PMID- 20591163 TI - Design and Organization of the Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT) Trial: a factorial trial evaluating the effects of corticosteroids, glucose control, and depth-of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. AB - BACKGROUND: The perioperative period is characterized by an intense inflammatory response. Perioperative inflammation promotes postoperative morbidity and increases mortality. Blunting the inflammatory response to surgical trauma might thus improve perioperative outcomes. We are studying three interventions that potentially modulate perioperative inflammation: corticosteroids, tight glucose control, and light anesthesia. METHODS/DESIGN: The DeLiT Trial is a factorial randomized single-center trial of dexamethasone vs placebo, intraoperative tight vs. conventional glucose control, and light vs deep anesthesia in patients undergoing major non-cardiac surgery. Anesthetic depth will be estimated with Bispectral Index (BIS) monitoring (Aspect medical, Newton, MA). The primary outcome is a composite of major postoperative morbidity including myocardial infarction, stroke, sepsis, and 30-day mortality. C-reactive protein, a measure of the inflammatory response, will be evaluated as a secondary outcome. One-year all-cause mortality as well as post-operative delirium will be additional secondary outcomes. We will enroll up to 970 patients which will provide 90% power to detect a 40% reduction in the primary outcome, including interim analyses for efficacy and futility at 25%, 50% and 75% enrollment. DISCUSSION: The DeLiT trial started in February 2007. We expect to reach our second interim analysis point in 2010. This large randomized controlled trial will provide a reliable assessment of the effects of corticosteroids, glucose control, and depth of-anesthesia on perioperative inflammation and morbidity from major non-cardiac surgery. The factorial design will enable us to simultaneously study the effects of the three interventions in the same population, both individually and in different combinations. Such a design is an economically efficient way to study the three interventions in one clinical trial vs three. TRIAL REGISTRATION: This trial is registered at Clinicaltrials.gov #: NTC00433251. PMID- 20591164 TI - Plasmodium falciparum PfA-M1 aminopeptidase is trafficked via the parasitophorous vacuole and marginally delivered to the food vacuole. AB - BACKGROUND: The Plasmodium falciparum PfA-M1 aminopeptidase, encoded by a single copy gene, displays a neutral optimal activity at pH 7.4. It is thought to be involved in haemoglobin degradation and/or invasion of the host cells. Although a series of inhibitors developed against PfA-M1 suggest that this enzyme is a promising target for therapeutic intervention, the biological function(s) of the three different forms of the enzyme (p120, p96 and p68) are not fully understood. Two recent studies using PfA-M1 transfections have also provided conflicting results on PfA-M1 localization within or outside the food vacuole. Alternative destinations, such as the nucleus, have also been proposed. METHODS: By using a combination of techniques, such as cellular and biochemical fractionations, biochemical analysis, mass-spectrometry, immunofluorescence assays and live imaging of GFP fusions to various PfA-M1 domains, evidence is provided for differential localization and behaviour of the three different forms of PfA-M1 in the infected red blood cell which had not been established before. RESULTS: The high molecular weight p120 form of PfA-M1, the only version of the protein with a hydrophobic transmembrane domain, is detected both inside the parasite and in the parasitophorous vacuole while the processed p68 form is strictly soluble and localized within the parasite. The transient intermediate and soluble p96 form is localized at the border of parasitophorous vacuole and within the parasite in a compartment sensitive to high concentrations of saponin. Upon treatment with brefeldin A, the PfA-M1 maturation is blocked and the enzyme remains in a compartment close to the nucleus. CONCLUSIONS: The PfA-M1 trafficking/maturation scenario that emerges from this data indicates that PfA-M1, synthesized as the precursor p120 form, is targeted to the parasitophorous vacuole via the parasite endoplasmic reticulum/Golgi, where it is converted into the transient p96 form. This p96 form is eventually redirected into the parasite to be converted into the processed p68 form that is only marginally delivered to the parasite food vacuole. These results provide insights on PfA-M1 topology regarding key compartments of the infected red blood cells that have important implications for the development of inhibitors targeting this plasmodial enzyme. PMID- 20591165 TI - The HAC1 gene from Pichia pastoris: characterization and effect of its overexpression on the production of secreted, surface displayed and membrane proteins. AB - BACKGROUND: The unfolded protein response (UPR) in eukaryotes upregulates factors that restore ER homeostasis upon protein folding stress and in yeast is activated by a non-conventional splicing of the HAC1 mRNA. The spliced HAC1 mRNA encodes an active transcription factor that binds to UPR-responsive elements in the promoter of UPR target genes. Overexpression of the HAC1 gene of S. cerevisiae can reportedly lead to increased production of heterologous proteins. To further such studies in the biotechnology favored yeast Pichia pastoris, we cloned and characterized the P. pastoris HAC1 gene and the splice event. RESULTS: We identified the HAC1 homologue of P. pastoris and its splice sites. Surprisingly, we could not find evidence for the non-spliced HAC1 mRNA when P. pastoris was cultivated in a standard growth medium without any endoplasmic reticulum stress inducers, indicating that the UPR is constitutively active to some extent in this organism. After identification of the sequence encoding active Hac1p we evaluated the effect of its overexpression in Pichia. The KAR2 UPR-responsive gene was strongly upregulated. Electron microscopy revealed an expansion of the intracellular membranes in Hac1p-overexpressing strains. We then evaluated the effect of inducible and constitutive UPR induction on the production of secreted, surface displayed and membrane proteins. Wherever Hac1p overexpression affected heterologous protein expression levels, this effect was always stronger when Hac1p expression was inducible rather than constitutive. Depending on the heterologous protein, co-expression of Hac1p increased, decreased or had no effect on expression level. Moreover, alpha-mating factor prepro signal processing of a G-protein coupled receptor was more efficient with Hac1p overexpression; resulting in a significantly improved homogeneity. CONCLUSIONS: Overexpression of P. pastoris Hac1p can be used to increase the production of heterologous proteins but needs to be evaluated on a case by case basis. Inducible Hac1p expression is more effective than constitutive expression. Correct processing and thus homogeneity of proteins that are difficult to express, such as GPCRs, can be increased by co-expression with Hac1p. PMID- 20591167 TI - Improved IBD detection using incomplete haplotype information. AB - BACKGROUND: The availability of high density genetic maps and genotyping platforms has transformed human genetic studies. The use of these platforms has enabled population-based genome-wide association studies. However, in inheritance based studies, current methods do not take full advantage of the information present in such genotyping analyses. RESULTS: In this paper we describe an improved method for identifying genetic regions shared identical-by-descent (IBD) from recent common ancestors. This method improves existing methods by taking advantage of phase information even if it is less than fully accurate or missing. We present an analysis of how using phase information increases the accuracy of IBD detection compared to using only genotype information. CONCLUSIONS: Our algorithm should have utility in a wide range of genetic studies that rely on identification of shared genetic material in large families or small populations. PMID- 20591166 TI - Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis. AB - BACKGROUND: Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation. METHODS: Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL). RESULTS: Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21. CONCLUSIONS: In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences. PMID- 20591168 TI - The FIMP Medicines for Children Research Network. AB - The European Paediatric Regulation (EUPR) calls for the fostering of high quality ethical research and medicinal products to be used in children. The EUPR provides the background, goals, and requirements for paediatric clinical trials. Paediatric clinical trials in children are mandatory to generate data on new drugs as well as on drugs used off-label or for unlicensed indications. The Family Paediatricians Medicines for Children Research Network (FIMP-MCRN) was established in 2003 with the aim of developing competence, infrastructure, networking and education for paediatric clinical trials. The network, consisting of twenty Paediatric Regional Networks has progressed very well and has achieved valuable improvements concerning the conduct of paediatric clinical trials. Furthermore, ad hoc training programs have incremented knowledge about clinical trials in Family Paediatrician Investigators (FPI) and have made medical professionals as well as the public aware of the need and advantages of trials in children. PMID- 20591169 TI - Characterisation of the binding properties of Bacillus thuringiensis 18 toxin on leukaemic cells. AB - BACKGROUND: Various strains of Bacillus thuringiensis (Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS. METHODS: In homologous competitive binding study, the purified toxin was labelled with biotin and allowed to compete with unlabelled toxin for binding sites on CEM-SS and its dissociation constant (Kd) was determined. Comparisons were made with CCRF-SB, CCRF-HSB-2 and MCF-7. In heterologous competitive binding study, biotinylated toxin competition was determined with two other Bt toxins (crude Btj and crude Bt 22) and anticancer drugs (cisplatin, doxorubicin, etoposide, navelbine and methotrexate). To localise the binding site under the confocal microscope, the biotinylated toxin was tagged with FITC-conjugated streptavidin. RESULTS: Homologous competitive binding assays revealed decreasing binding affinity of Bt 18 toxin for CEM-SS, CCRF-SB, and CCRF-HSB-2 with Kd of 8.44 nM, 14.98 nM and 17.71 nM respectively. Kd for MCF-7 was not determined as the inhibitory concentration (IC50) was not reached. Heterologous competitive study showed little competition (< 30%) between biotinylated Bt 18 toxin and all test compounds used. Confocal microscopy revealed binding of toxin at the periphery of the cell. CONCLUSIONS: It was postulated that purified Bt 18 toxin binds on the cell surface of CEM-SS and the mechanism of cell death may differ from that of Btj toxin, Bt 22 toxin and all five anticancer drugs used in this study, since it did not significantly compete with these compounds for the same binding site. PMID- 20591170 TI - The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells. AB - BACKGROUND: The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFbeta is a transcriptional co activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFbeta is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFbeta-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFbeta. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFbeta expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFbeta. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. RESULTS: We show that CBFbeta is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFbeta contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFbeta is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFbeta is recruited to both the Osteopontin and the Galectin-3 promoters. CONCLUSIONS: CBFbeta is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFbeta is required for expression of several Runx2 target genes known to be involved in cell invasion. However, whilst CBFbeta is essential for invasion, not all Runx2-target genes require CBFbeta. We conclude that CBFbeta is required for a subset of Runx2-target genes that are sufficient to maintain the invasive phenotype of the cells. These findings suggest that the interaction between Runx2 and CBFbeta might represent a viable target for therapeutic intervention to inhibit bone metastasis. PMID- 20591171 TI - Study protocol: home-based telehealth stroke care: a randomized trial for veterans. AB - BACKGROUND: Stroke is one of the most disabling and costly impairments of adulthood in the United States. Stroke patients clearly benefit from intensive inpatient care, but due to the high cost, there is considerable interest in implementing interventions to reduce hospital lengths of stay. Early discharge rehabilitation programs require coordinated, well-organized home-based rehabilitation, yet lack of sufficient information about the home setting impedes successful rehabilitation. This trial examines a multifaceted telerehabilitation (TR) intervention that uses telehealth technology to simultaneously evaluate the home environment, assess the patient's mobility skills, initiate rehabilitative treatment, prescribe exercises tailored for stroke patients and provide periodic goal oriented reassessment, feedback and encouragement. METHODS: We describe an ongoing Phase II, 2-arm, 3-site randomized controlled trial (RCT) that determines primarily the effect of TR on physical function and secondarily the effect on disability, falls-related self-efficacy, and patient satisfaction. Fifty participants with a diagnosis of ischemic or hemorrhagic stroke will be randomly assigned to one of two groups: (a) TR; or (b) Usual Care. The TR intervention uses a combination of three videotaped visits and five telephone calls, an in home messaging device, and additional telephonic contact as needed over a 3-month study period, to provide a progressive rehabilitative intervention with a treatment goal of safe functional mobility of the individual within an accessible home environment. Dependent variables will be measured at baseline, 3-, and 6 months and analyzed with a linear mixed-effects model across all time points. DISCUSSION: For patients recovering from stroke, the use of TR to provide home assessments and follow-up training in prescribed equipment has the potential to effectively supplement existing home health services, assist transition to home and increase efficiency. This may be particularly relevant when patients live in remote locations, as is the case for many veterans. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT00384748. PMID- 20591172 TI - Occult gallbladder carcinoma presenting as a primary ovarian tumor in two women: two case reports and a review of the literature. AB - INTRODUCTION: The ovary is a common site of metastasis from various organs. However, little is known about gallbladder carcinoma metastasizing to the ovaries and presenting as a primary ovarian tumor. CASE PRESENTATION: We report two cases of a metastatic gallbladder carcinoma which mimicked a primary ovarian tumor in a 35-year-old and a 62-year-old North Indian woman. Clinically, both our patients presented with abdominal masses without obvious signs and symptoms related to gallbladder carcinoma. Radiology suggested the possibility of a primary ovarian tumor with chronic cholecystitis and cholelithiasis. The gross features also mimicked a primary malignant ovarian tumor in the first case and a benign mucinous neoplasm in the second case. Exact diagnoses could only be made after thorough sampling from both the ovaries and gallbladder. CONCLUSIONS: Gallbladder carcinoma with metastasis to the ovaries can mimic both malignant and benign primary ovarian tumors. Extensive cystic change in the ovary due to metastasis from gallbladder carcinoma has rarely been reported. A high index of suspicion and thorough sampling are essential to avoid misdiagnosis in such cases. PMID- 20591173 TI - A multi-center, randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy, safety, and pharmacokinetics of intravenous ibuprofen for the treatment of fever in critically ill and non-critically ill adults. AB - INTRODUCTION: Hospitalized patients are often unable to ingest or tolerate oral antipyretics and recently an aqueous formulation of intravenous (IV) ibuprofen was approved by the US-FDA for the reduction of fever in adults. METHODS: We evaluated IV ibuprofen to reduce fever exceeding 101.0 degrees F, measured as the percentage of subjects achieving a temperature <101.0 degrees F at four hours after a single dose of IV ibuprofen vs. placebo. Secondary evaluations included the effect on temperature at 24 hours. Nine sites randomized patients to receive either a placebo or IV ibuprofen (100, 200, or 400 mg), and patients were given four hours for six doses. Subjects were excluded for platelet count <30 k and/or creatinine >3.0 mg/dL. RESULTS: At entry, there were no significant baseline differences between the IV ibuprofen group and placebo, n = 120. At four hours, the number (percentage) with T<101.0 degrees F was: Placebo n = 9/28 (32%); 100 mg IV ibuprofen n = 19/31 (61%), P = 0.0264; 200 mg IV ibuprofen n = 21/30 (70%) P = 0.0043; 400 mg IV ibuprofen n = 24/31 (77%) P = 0.0005. A total of 53/120 patients (44%) were prospectively defined as critically ill at baseline and similar temperature reductions were observed in this subgroup. There were no statistically significant differences between treatment groups or when compared to placebo in transfusion, bleeding, renal failure or mortality. CONCLUSIONS: All doses of IV ibuprofen tested reduced fever at four hours and throughout the first 24 hours of dosing. The 400 mg dose was effective in lowering temperature to normal and maintaining this over the first 24 hours of dosing. IV ibuprofen was effective in reducing fevers in critically ill and non-critically ill groups. Following 24 hours of administration of IV ibuprofen, no clinically significant differences in any safety parameter including renal function or bleeding occurred through the 28-day follow-up period. TRIAL REGISTRATIONS: Clinicaltrials.gov registration number: NCT01131000. PMID- 20591174 TI - Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients. AB - BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients. METHODS: We enrolled 88 consecutive HIV-1 infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively. RESULTS: The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p < 0.0001 and p < 0.001, respectively). Using the average OARI as the dependent variable, total serum cholesterol level, HDL, triglycerides, glycemia, sex, blood pressure, age and PRFT were independent factors associated with OARI. A PRFT of 6.1 mm was the most discriminatory value for predicting an OARI > 0.74 (sensitivity 78.9%, specificity 82.8%). CONCLUSIONS: Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients. PMID- 20591175 TI - MetaBar - a tool for consistent contextual data acquisition and standards compliant submission. AB - BACKGROUND: Environmental sequence datasets are increasing at an exponential rate; however, the vast majority of them lack appropriate descriptors like sampling location, time and depth/altitude: generally referred to as metadata or contextual data. The consistent capture and structured submission of these data is crucial for integrated data analysis and ecosystems modeling. The application MetaBar has been developed, to support consistent contextual data acquisition. RESULTS: MetaBar is a spreadsheet and web-based software tool designed to assist users in the consistent acquisition, electronic storage, and submission of contextual data associated to their samples. A preconfigured Microsoft Excel spreadsheet is used to initiate structured contextual data storage in the field or laboratory. Each sample is given a unique identifier and at any stage the sheets can be uploaded to the MetaBar database server. To label samples, identifiers can be printed as barcodes. An intuitive web interface provides quick access to the contextual data in the MetaBar database as well as user and project management capabilities. Export functions facilitate contextual and sequence data submission to the International Nucleotide Sequence Database Collaboration (INSDC), comprising of the DNA DataBase of Japan (DDBJ), the European Molecular Biology Laboratory database (EMBL) and GenBank. MetaBar requests and stores contextual data in compliance to the Genomic Standards Consortium specifications. The MetaBar open source code base for local installation is available under the GNU General Public License version 3 (GNU GPL3). CONCLUSION: The MetaBar software supports the typical workflow from data acquisition and field-sampling to contextual data enriched sequence submission to an INSDC database. The integration with the megx.net marine Ecological Genomics database and portal facilitates georeferenced data integration and metadata-based comparisons of sampling sites as well as interactive data visualization. The ample export functionalities and the INSDC submission support enable exchange of data across disciplines and safeguarding contextual data. PMID- 20591176 TI - Neoplastic transformation of breast epithelial cells by genotoxic stress. AB - BACKGROUND: Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation. METHODS: To study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray) or cigarette smoke condensate (Csc - 10 microgram/ml of medium) or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment. RESULTS: Exposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation. CONCLUSIONS: The results indicate that when normal breast cells are exposed to low dose radiation in combination with cigarette smoke condensate a phenotype is generated that exhibits traits indicative of neoplastic transformation. More importantly, this is the first study to provide a new insight into a possible etiology for breast cancer formation in individuals exposed to low dose radiation and tobacco smoke. PMID- 20591177 TI - Fixation strength of biocomposite wedge interference screw in ACL reconstruction: effect of screw length and tunnel/screw ratio. A controlled laboratory study. AB - BACKGROUND: Primary stability of the graft is essential in anterior cruciate ligament surgery. An optimal method of fixation should be easy to insert and provide great resistance against pull-out forces.A controlled laboratory study was designed to test the primary stability of ACL tendinous grafts in the tibial tunnel. The correlation between resistance to traction forces and the cross section and length of the screw was studied. METHODS: The tibial phase of ACL reconstruction was performed in forty porcine tibias using digital flexor tendons of the same animal. An 8 mm tunnel was drilled in each specimen and two looped tendons placed as graft. Specimens were divided in five groups according to the diameter and length of the screw used for fixation. Wedge interference screws were used. Longitudinal traction was applied to the graft with a Servohydraulic Fatigue System. Load and displacement were controlled and analyzed. RESULTS: The mean loads to failure for each group were 295,44 N (Group 1; 9 x 23 screw), 564,05 N (Group 2; 9 x 28), 614,95 N (Group 3; 9 x 35), 651,14 N (Group 4; 10 x 28) and 664,99 (Group 5; 10 x 35). No slippage of the graft was observed in groups 3, 4 and 5. There were significant differences in the load to failure among groups (ANOVA/P < 0.001). CONCLUSIONS: Longer and wider interference screws provide better fixation in tibial ACL graft fixation. Short screws (23 mm) do not achieve optimal fixation and should be implanted only with special requirements. PMID- 20591178 TI - On the use of resampling tests for evaluating statistical significance of binding site co-occurrence. AB - BACKGROUND: In eukaryotes, most DNA-binding proteins exert their action as members of large effector complexes. The presence of these complexes are revealed in high-throughput genome-wide assays by the co-occurrence of the binding sites of different complex components. Resampling tests are one route by which the statistical significance of apparent co-occurrence can be assessed. RESULTS: We have investigated two resampling approaches for evaluating the statistical significance of binding-site co-occurrence. The permutation test approach was found to yield overly favourable p-values while the independent resampling approach had the opposite effect and is of little use in practical terms. We have developed a new, pragmatically-devised hybrid approach that, when applied to the experimental results of an Polycomb/Trithorax study, yielded p-values consistent with the findings of that study. We extended our investigations to the FL method developed by Haiminen et al, which derives its null distribution from all binding sites within a dataset, and show that the p-value computed for a pair of factors by this method can depend on which other factors are included in that dataset. Both our hybrid method and the FL method appeared to yield plausible estimates of the statistical significance of co-occurrences although our hybrid method was more conservative when applied to the Polycomb/Trithorax dataset.A high performance parallelized implementation of the hybrid method is available. CONCLUSIONS: We propose a new resampling-based co-occurrence significance test and demonstrate that it performs as well as or better than existing methods on a large experimentally-derived dataset. We believe it can be usefully applied to data from high-throughput genome-wide techniques such as ChIP-chip or DamID. The Cooccur package, which implements our approach, accompanies this paper. PMID- 20591179 TI - Treatment planning using MRI data: an analysis of the dose calculation accuracy for different treatment regions. AB - BACKGROUND: Because of superior soft tissue contrast, the use of magnetic resonance imaging (MRI) as a complement to computed tomography (CT) in the target definition procedure for radiotherapy is increasing. To keep the workflow simple and cost effective and to reduce patient dose, it is natural to strive for a treatment planning procedure based entirely on MRI. In the present study, we investigate the dose calculation accuracy for different treatment regions when using bulk density assignments on MRI data and compare it to treatment planning that uses CT data. METHODS: MR and CT data were collected retrospectively for 40 patients with prostate, lung, head and neck, or brain cancers. Comparisons were made between calculations on CT data with and without inhomogeneity corrections and on MRI or CT data with bulk density assignments. The bulk densities were assigned using manual segmentation of tissue, bone, lung, and air cavities. RESULTS: The deviations between calculations on CT data with inhomogeneity correction and on bulk density assigned MR data were small. The maximum difference in the number of monitor units required to reach the prescribed dose was 1.6%. This result also includes effects of possible geometrical distortions. CONCLUSIONS: The dose calculation accuracy at the investigated treatment sites is not significantly compromised when using MRI data when adequate bulk density assignments are made. With respect to treatment planning, MRI can replace CT in all steps of the treatment workflow, reducing the radiation exposure to the patient, removing any systematic registration errors that may occur when combining MR and CT, and decreasing time and cost for the extra CT investigation. PMID- 20591180 TI - Predictors of pneumococcal vaccination among older adults with pneumonia: findings from the Community Acquired Pneumonia Impact Study. AB - BACKGROUND: The incidence of community-acquired pneumonia (CAP) almost triples for older adults aged 65 years or older. In Canada, CAP is a leading cause of hospital admissions and mortality. Although CAP is very prevalent, complications due to CAP may be reduced with the pneumococcal polysaccharide vaccine (PPV). The purpose of this study was to identify predictors of pneumococcal vaccination among community-dwelling older adults with clinically diagnosed CAP. METHODS: A telephone survey was used to collect detailed information from adults aged 60 years and older with clinically diagnosed CAP. This was a community wide study with participants being recruited from all radiology clinics in one Ontario community. RESULTS: The most important predictors of pneumococcal vaccination among older adults included: getting an influenza vaccine within the past year (OR 14.5, 95% CI 4.27 to 49.0); at least weekly contact with a friend (OR 3.97, 95% CI 1.71 to 9.24); having one or more co-morbidities/chronic conditions (OR 3.64, 95% CI 1.60 to 8.28); being 70 years of age or older (OR 2.56, 95% CI 1.21 to 5.40); having health problems that limited physical activities (OR 5.37, 95% CI 1.49 to 19.3); having little or no bodily pain (OR 2.90, 95% CI 1.25 to 6.73); and reporting having spiritual values or religious faith (OR 3.47, 95% CI 1.03 to 11.67). CONCLUSIONS: A wide range of factors, including demographic, co morbidity, quality of life, social support and lifestyle were found to be associated with pneumococcal vaccination status among older adults with clinically diagnosed CAP. The findings from this study could inform future pneumococcal immunization strategies by identifying individuals who are least likely to receive the PPV. PMID- 20591181 TI - Mobile element scanning (ME-Scan) by targeted high-throughput sequencing. AB - BACKGROUND: Mobile elements (MEs) are diverse, common and dynamic inhabitants of nearly all genomes. ME transposition generates a steady stream of polymorphic genetic markers, deleterious and adaptive mutations, and substrates for further genomic rearrangements. Research on the impacts, population dynamics, and evolution of MEs is constrained by the difficulty of ascertaining rare polymorphic ME insertions that occur against a large background of pre-existing fixed elements and then genotyping them in many individuals. RESULTS: Here we present a novel method for identifying nearly all insertions of a ME subfamily in the whole genomes of multiple individuals and simultaneously genotyping (for presence or absence) those insertions that are variable in the population. We use ME-specific primers to construct DNA libraries that contain the junctions of all ME insertions of the subfamily, with their flanking genomic sequences, from many individuals. Individual-specific "index" sequences are designed into the oligonucleotide adapters used to construct the individual libraries. These libraries are then pooled and sequenced using a ME-specific sequencing primer. Mobile element insertion loci of the target subfamily are uniquely identified by their junction sequence, and all insertion junctions are linked to their individual libraries by the corresponding index sequence. To test this method's feasibility, we apply it to the human AluYb8 and AluYb9 subfamilies. In four individuals, we identified a total of 2,758 AluYb8 and AluYb9 insertions, including nearly all those that are present in the reference genome, as well as 487 that are not. Index counts show the sequenced products from each sample reflect the intended proportions to within 1%. At a sequencing depth of 355,000 paired reads per sample, the sensitivity and specificity of ME-Scan are both approximately 95%. CONCLUSIONS: Mobile Element Scanning (ME-Scan) is an efficient method for quickly genotyping mobile element insertions with very high sensitivity and specificity. In light of recent improvements to high-throughput sequencing technology, it should be possible to employ ME-Scan to genotype insertions of almost any mobile element family in many individuals from any species. PMID- 20591182 TI - Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006. AB - BACKGROUND: Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. METHODS: The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion. RESULTS: In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%). CONCLUSIONS: The observed increased risk for induced abortion among women with psychotropic medication highlights the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth. PMID- 20591184 TI - Wnt signal transduction pathway and apoptosis: a review. AB - The association between the wnt signaling pathway and apoptosis has become more firmly established in the recent scientific literature. Many reports indicate that the wnt signaling pathway regulates apoptosis through a variety of mechanisms.The activity of wnt signaling according to specific cellular environment stimuli can either foster or restrain the processes of apoptosis. Wnt signaling regulates the early and late stages of apoptosis in both development and cellular injury in populations of neurons, endothelial cells, vascular smooth muscle cells and cardiomyocytes.In this review I draw attention to genes and proteins of the wnt signaling pathway involved in apoptosis and describe some of their functional effects. PMID- 20591183 TI - Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways. AB - BACKGROUND: Organotin compounds (OTCs) have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT) compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC) of cells. METHOD: In the present study, the effects of triphenyltin chloride (TPTC) on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique. RESULTS: TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC) inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis. CONCLUSIONS: These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways. PMID- 20591185 TI - Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells. AB - BACKGROUND: Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. RESULTS: Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. CONCLUSION: Our results suggest that resistin induces expansion of functional Tregs only when co cultured with DCs. PMID- 20591186 TI - Low levels of nestmate discrimination despite high genetic differentiation in the invasive pharaoh ant. AB - BACKGROUND: Ants typically distinguish nestmates from non-nestmates based on the perception of colony-specific chemicals, particularly cuticular hydrocarbons present on the surface of the ants' exoskeleton. These recognition cues are believed to play an important role in the formation of vast so-called supercolonies that have been described for some invasive ant species, but general conclusions about the role of these cues are hampered by only few species being studied. Here we use data on cuticular hydrocarbons, aggression and microsatellite genetic markers to investigate the interdependence of chemical recognition cues, genetic distance and nestmate discrimination in the pharaoh ant (Monomorium pharaonis), a widespread pest species, and ask whether introduced populations of this species are genetically differentiated and exhibit intraspecific aggression. RESULTS: Microsatellite analyses of a total of 35 colonies from four continents revealed extremely high levels of genetic differentiation between almost all colonies (FST = 0.751 +/- 0.006 SE) and very low within-colony diversity. This implies that at least 34 and likely hundreds more independent lineages of this ant have spread worldwide. Aggression tests involving workers from 14 different colonies showed only low levels of aggression, even between colonies that were geographically and/or genetically very distant. Chemical analyses of groups of worker ants showed that all colonies had the same cuticular compounds, which varied only quantitatively among colonies. There was a positive correlation between geographical and genetic distance, but no other significant relationships were detected between aggression, chemical profile, genetic distance and geographical distance. CONCLUSIONS: The pharaoh ant has a global invasion history of numerous independent introductions resulting in genetically highly differentiated colonies typically displaying surprisingly low levels of intraspecific aggression, a behaviour that may have evolved in the native range or by lineage selection in the introduced range. PMID- 20591187 TI - The antigen presentation function of bone marrow-derived mast cells is spatiotemporally restricted to a subset expressing high levels of cell surface FcepsilonRI and MHC II. AB - BACKGROUND: At present, it is highly controversial whether pure mast cells can serve as antigen presenting cells, and it is not known whether the capacity of antigen presenting function is temporally restricted to a particular subset of differentiated mast cells. Evidence is presented for a novel surface FcepsilonRIhi , MHC II +, and c-kit + pure mast cell subset, temporally restricted as antigen-presenting cells in the immune axis of T-cell activation. RESULTS: Bone marrow-derived mast cells (BMMC) cultured in the presence of IL-3 for three weeks are pure mast cells based on surface expression of lineage specific marker, c-kit and FcepsilonRI. Herein we present the first demonstration that approximately 98.7% c-kit + and FcepsilonRI expressing BMMC, further depleted of any contaminated professional antigen-presenting cells, are still fully capable of presenting antigens, i.e., OVA protein, OVA peptide, and IgE-TNP OVA, to OVA peptide-specific T-cell hybridomas. Notably, IgE-dependent antigen presentation is more efficient compared to that resulting from direct antigen uptake. Importantly, we present the novel finding that only surface FcepsilonRIhi mast cells, also expressing surface MHC II exhibited antigen-presenting function. In contrast, surface FcepsilonRIlo mast cells without expressing surface MHC II were not capable of antigen presentation. Interestingly, the antigen-presenting function of BMMC was irrevocably lost during the third and fourth week in IL-3 or SCF containing cultures. CONCLUSIONS: This is the first observation to attribute a spatiotemporally restricted antigen-presenting function to a subset of three week old pure BMMC expressing both high levels of surface FcepsilonRI and surface MHC II. We propose that mast cells play an important role in immune deviating and/or sustaining the activation of infiltrating CD4 T-cells, and modulating T cell mediated allergic inflammation via its flexibility to present antigens and antigen-IgE complexes. PMID- 20591188 TI - Presence of a classical RRM-fold palm domain in Thg1-type 3'- 5'nucleic acid polymerases and the origin of the GGDEF and CRISPR polymerase domains. AB - BACKGROUND: Almost all known nucleic acid polymerases catalyze 5'-3' polymerization by mediating the attack on an incoming nucleotide 5' triphosphate by the 3'OH from the growing polynucleotide chain in a template dependent or independent manner. The only known exception to this rule is the Thg1 RNA polymerase that catalyzes 3'-5' polymerization in vitro and also in vivo as a part of the maturation process of histidinyl tRNA. While the initial reaction catalyzed by Thg1 has been compared to adenylation catalyzed by the aminoacyl tRNA synthetases, the evolutionary relationships of Thg1 and the actual nature of the polymerase reaction catalyzed by it remain unclear. RESULTS: Using sensitive profile-profile comparison and structure prediction methods we show that the catalytic domain Thg1 contains a RRM (ferredoxin) fold palm domain, just like the viral RNA-dependent RNA polymerases, reverse transcriptases, family A and B DNA polymerases, adenylyl cyclases, diguanylate cyclases (GGDEF domain) and the predicted polymerase of the CRISPR system. We show just as in these polymerases, Thg1 possesses an active site with three acidic residues that chelate Mg++ cations. Based on this we predict that Thg1 catalyzes polymerization similarly to the 5'-3' polymerases, but uses the incoming 3' OH to attack the 5' triphosphate generated at the end of the elongating polynucleotide. In addition we identify a distinct set of residues unique to Thg1 that we predict as comprising a second active site, which catalyzes the initial adenylation reaction to prime 3'-5' polymerization. Based on contextual information from conserved gene neighborhoods we show that Thg1 might function in conjunction with a polynucleotide kinase that generates an initial 5' phosphate substrate for it at the end of a RNA molecule. In addition to histidinyl tRNA maturation, Thg1 might have other RNA repair roles in representatives from all the three superkingdoms of life as well as certain large DNA viruses. We also present evidence that among the polymerase-like domains Thg1 is most closely related to the catalytic domains of the GGDEF and CRISPR polymerase proteins. CONCLUSION: Based on this relationship and the phyletic patterns of these enzymes we infer that the Thg1 protein is likely to represent an archaeo-eukaryotic branch of the same clade of proteins that gave rise to the mobile CRISPR polymerases and in bacteria spawned the GGDEF domains. Thg1 is likely to be close to the ancestral version of this family of enzymes that might have played a role in RNA repair in the last universal common ancestor. PMID- 20591189 TI - Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study. AB - BACKGROUND: There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT). We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results. METHODS: We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59) and those from normal-appearing urothelium (N = 234) were evaluated separately. RESULTS: Bladder cancer was observed in 23 cases (39.0%) who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS) only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1%) who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis. CONCLUSIONS: Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline. PMID- 20591190 TI - Acute onset lactobacillus endophthalmitis after trabeculectomy: a case report. AB - INTRODUCTION: We report a case of early lactobacillus endophthalmitis which occurred ten days after trabeculectomy. CASE PRESENTATION: A 76-year-old Caucasian diabetic woman underwent uncomplicated trabeculectomy with a collagen implant as an adjunct, in her left phakic eye, for the treatment of uncontrolled open-angle glaucoma. Ten days post-operatively, our patient complained of left phakic eye discharge pain and visual acuity decreased to "light-perception". The anterior chamber had 3+ cells and flare, and there was also 2 mm layered hypopyon. Vitreous involvement was present obscuring visualization of the fundus. On the same day our patient underwent vitrectomy surgery and intra-vitreal and systemic antibiotics were administered. Vitreous cultures grew Lactobacillus brevis. Our patient responded well to treatment and 30 days after vitrectomy visual acuity improved to 1/10. Six months later our patient underwent cataract surgery. Eight months after initial surgery visual acuity was 2/10 and intra ocular pressure was 14 mmHg without any anti-glaucoma medication. CONCLUSIONS: This is the first report of acute lactobacillus endophthalmitis in the phakic eye of a diabetic patient after trabeculectomy. Glaucoma surgeons should be aware of the potential for acute post-operative endophthalmitis due to rare microorganisms, such as lactobacillus, in glaucoma filtration surgery, especially in diabetic patients. The literature shows an increased risk of endophthalmitis when anti-metabolites are used in conjunction with trabeculectomy. Perhaps, any type of wound healing modulation, such as collagen or mitomycin-C may increase this risk. However, it is unclear at this time and more studies need to be done. In this single case, vitrectomy combined with intra-vitreal and systemic antibiotics were efficient in limiting the devastating sequels of this complication. PMID- 20591191 TI - Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol. AB - BACKGROUND: Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. METHODS/DESIGN: Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082. PMID- 20591192 TI - Rectal ulceration caused by the anti-anginal nicorandil: Case report of a preventable complication. AB - The association of the anti-anginal drug nicorandil with oral and anal ulceration is becoming more widely recognised, but there are no reports of isolated nicorandil-induced rectal ulceration. Awareness of this condition is poor, and patients often undergo unnecessary surgery for a condition which resolves on stopping the medication.We report a case of nicorandil-induced rectal ulceration causing rectal bleeding. The patient was spared surgery after awareness of the link with this drug.This diagnosis should be considered in patients with unexplained gastrointestinal ulceration after exclusion of serious underlying causes. We hope this report will increase awareness amongst physicians and surgeons of this reversible condition. PMID- 20591193 TI - The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors. AB - A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11REN (KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells. PMID- 20591194 TI - 'Relief of oppression': an organizing principle for researchers' obligations to participants in observational studies in the developing world. AB - BACKGROUND: A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research related needs of participants, to aspects of their basic life circumstances. DISCUSSION: In this paper, we describe the Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms. SUMMARY: The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research. PMID- 20591195 TI - Anti-centromere antibody-seropositive Sjogren's syndrome differs from conventional subgroup in clinical and pathological study. AB - BACKGROUND: To clarify the clinicopathological characteristics of primary Sjogren's syndrome (pSS) with anti-centromere antibody (ACA). METHODS: Characteristics of 14 patients of pSS with ACA were evaluated. All patients were anti-SS-A/Ro and SS-B/La antibodies negative (ACA+ group) without sclerodactyly. The prevalence of Raynaud's phenomenon (RP), titer of IgG and focus score (FS) in the minor salivary glands (MSGs) were determined. Quantification analysis of Azan Mallory staining was performed to detect collagenous fiber. Forty eight patients in whom ACA was absent were chosen as the conventional (ACA-) pSS group. RESULTS: Prevalence of ACA+ SS patients was 14 out of 129 (10.85%) pSS patients. RP was observed in 61.5% of the patients with ACA. The level of IgG in the ACA+ group was significantly lower than that of the ACA- group (p = 0.018). Statistical difference was also found in the FS of MSGs from the ACA+ group (1.4 +/- 1.0) as compared with the ACA- group (2.3 +/- 1.6) (p = 0.035). In contrast, the amount of fibrous tissue was much higher in the ACA+ group (65052.2 +/- 14520.6 microm(2) versus 26251.3 +/- 14249.8 microm(2)) (p = 1.3 x 10(-12)). CONCLUSIONS: Low cellular infiltration but with an increase in fibrous tissues may explain the clinical feature of a high prevalence of RP and normal IgG concentration in ACA+ pSS. PMID- 20591196 TI - Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review. AB - BACKGROUND: This study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC). METHODS: Thirty-seven patients who underwent a curative repeat hepatectomy in our hospital were retrospectively studied. An extensive database literature search was performed to obtain for all relevant studies. RESULTS: In our series, there were no perioperative deaths during repeat hepatectomy for recurrent HCC. Patients survival after repeat hepatectomy were similar to 429 patients undergoing initial hepatectomy. A computerized search of the Medline and PubMed databases found 29 retrospective studies providing relevant data in 1149 patients were included for appraisal and data extraction. After the repeat hepatectomy, postoperative morbidity ranged from 6.2% to 68.2% with a median per cohort of 23.5 per cent. There were 7 perioperative deaths (0.7 per cent of 993 for whom mortality data were provided). The overall median survival ranged from 21 to 61.5 months, with 1 , 3-, and 5-year survival of 69.0% to 100%, 21.0% to 87.0%, and 25.0% to 87.0%, respectively. CONCLUSIONS: Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC. However, the findings have to be carefully interpreted due to the lower level of evidence. A randomized controlled study is needed to compare repeat hepatectomy and other modalities for recurrent HCC. PMID- 20591197 TI - The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study. AB - BACKGROUND: Atherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR). METHODS: Twenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5 T high-spatial-resolution, multi contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm) were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness)/Maximum wall thickness] >or= 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software. RESULTS: One hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric) was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70) after adjustment for atherosclerotic risk factors and wall area. CONCLUSIONS: Plaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery. PMID- 20591198 TI - Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association. AB - BACKGROUND: In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML) and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols. METHODS: Archival, diagnostic ML biopsies (N = 336), available sera (N = 35) screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH) in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174) were analyzed by histopathology and immunohistochemistry (IHC). Selected biopsies were characterized by flow-cytometry (FC) for DNA ploidy (N = 60) and some by in-situ hybridization (ISH) for EBV-encoded RNA (EBER, N = 37). RESULTS: A third (38.8%, 109/281) of the ML patients with available clinical information had extranodal disease presentation. A total of 158 out of 174 biopsies selected for immunophenotyping were confirmed to be ML which were mostly (84. 8%, 134/158) non Hodgkin lymphoma (NHL). Most (83.6%, 112/134) of NHL were B-cell lymphomas (BCL) (CD20+), of which 50.9%, (57/112) were diffuse large B-cell (DLBCL). Out of the 158 confirmed MLs, 22 (13.9%) were T-cell [CD3+] lymphomas (TCL) and 24 (15.2%) were Hodgkin lymphomas (HL) [CD30+]. Furthermore, out of the 60 FC analyzed ML cases, 27 (M:F ratio 2:1) were DLBCL, a slight majority (55.6%, 15/27) with activated B-cell like (ABC) and 45% (12/27) with germinal center B-cell like (GCB) immunophenotype. Overall, 40% (24/60) ML were aneuploid mostly (63.0%, 17/27) the DLBCL and TCL (54.5%, 6/11). DNA index (DI) of FC-analyzed ML ranged from 1.103-2.407 (median = 1.51) and most (75.0%) aneuploid cases showed high (>40%) cell proliferation by Ki-67 reactivity. The majority (51.4%, 19/37) of EBER ISH analyzed lymphoma biopsies were positive. Of the serologically tested MLs, 40.0% (14/35) were HIV positive, mostly with high (> or =40.0%) Ki-67 reactivity. CONCLUSIONS: According to the 2001 WHO Classification, most subtypes are represented in Tanzanian ML. Extranodal presentation was common among MNH lymphoma patients who also showed high aneuploidy, tumor proliferation (KI-67) and EBER positivity. DLBCL was frequent and phenotype heterogeneity appeared similar to observations in Western countries suggesting applicability of established intervention approaches. HIV was apparently associated with high ML cell proliferation but extended studies are needed to clarify this. PMID- 20591199 TI - Transcriptional regulation of the grape cytochrome P450 monooxygenase gene CYP736B expression in response to Xylella fastidiosa infection. AB - BACKGROUND: Plant cytochrome P450 monooxygenases (CYP) mediate synthesis and metabolism of many physiologically important primary and secondary compounds that are related to plant defense against a range of pathogenic microbes and insects. To determine if cytochrome P450 monooxygenases are involved in defense response to Xylella fastidiosa (Xf) infection, we investigated expression and regulatory mechanisms of the cytochrome P450 monooxygenase CYP736B gene in both disease resistant and susceptible grapevines. RESULTS: Cloning of genomic DNA and cDNA revealed that the CYP736B gene was composed of two exons and one intron with GT as a donor site and AG as an acceptor site. CYP736B transcript was up-regulated in PD-resistant plants and down-regulated in PD-susceptible plants 6 weeks after Xf inoculation. However, CYP736B expression was very low in stem tissues at all evaluated time points. 5'RACE and 3'RACE sequence analyses revealed that there were three candidate transcription start sites (TSS) in the upstream region and three candidate polyadenylation (PolyA) sites in the downstream region of CYP736B. Usage frequencies of each transcription initiation site and each polyadenylation site varied depending on plant genotype, developmental stage, tissue, and treatment. These results demonstrate that expression of CYP736B is regulated developmentally and in response to Xf infection at both transcriptional and post-transcriptional levels. Multiple transcription start and polyadenylation sites contribute to regulation of CYP736B expression. CONCLUSIONS: This report provides evidence that the cytochrome P450 monooxygenase CYP736B gene is involved in defense response at a specific stage of Xf infection in grapevines; multiple transcription initiation and polyadenylation sites exist for CYP736B in grapevine; and coordinative and selective use of transcription initiation and polyadenylation sites play an important role in regulation of CYP736B expression during growth, development and response to Xf infection. PMID- 20591200 TI - Mortality in Western Australian seniors with chronic respiratory diseases: a cohort study. AB - BACKGROUND: Relatively few studies have examined survival by pharmacotherapy level and the effects of patient characteristics on mortality by pharmacotherapy level in older chronic respiratory disease (CRD) patients. This study aimed to investigate these issues in older (> or = 65) CRD patients in Western Australia. METHODS: We identified 108,312 patients > or = 65 years with CRD during 1992-2006 using linked medical, pharmaceutical, hospital and mortality databases held by the Commonwealth and State governments. Pharmacotherapy classification levels were designed by a clinical consensus panel. Cox regression was used to investigate the study aim. RESULTS: Patients using only short acting bronchodilators experienced similar, but slightly worse survival than patients in the highest pharmacotherapy level group using high dose inhaled corticosteroids (ICS) +/- long acting bronchodilators (LABs) +/- oral steroids. Patients using low to medium dose ICS +/- LABs experienced relatively better survival. Also, male gender was associated with all-cause mortality in all patients (HR = 1.72, 95% CI 1.65-1.80) and especially in those in the highest pharmacotherapy level group (HR = 1.97, 95%CI = 1.84-2.10). The P-value of interaction between gender and pharmacotherapy level for the effect on all-cause death was significant (0.0003). CONCLUSIONS: Older patients with CRD not using ICS experienced the worst survival in this study and may benefit from an escalation in therapeutic regime. Males had a higher risk of death than females, which was more pronounced in the highest pharmacotherapy level group. Hence, primary health care should more actively direct disease management to mild-to-moderate disease patients. PMID- 20591201 TI - Hand-made biology. PMID- 20591202 TI - Postpartum education for contraception: a systematic review. AB - Contraceptive education is generally considered a standard component of postpartum care, but the effectiveness is seldom examined. Two-thirds of postpartum women may have unmet needs for contraception, and many adolescents become pregnant again within a year of giving birth. Women may prefer to discuss contraception prenatally or after hospital discharge. The objective of this systematic review was to assess the effects of educational interventions for postpartum mothers about contraceptive use. We searched computerized databases for randomized controlled trials that evaluated the effectiveness of postpartum contraceptive education. The intervention must have started within 1 month after delivery. The Mantel-Haenszel odds ratio was calculated with 95% confidence interval for the dichotomous outcomes. Eight trials met the inclusion criteria. Of 4 short-term interventions, 1 did not have sufficient data and 1 was statistically underpowered. The remaining 2 showed a positive effect on contraceptive use. Of 4 multifaceted programs, 2 showed fewer pregnancies or births among adolescents in the experimental group that had enhanced services, and 1 structured home-visiting program showed more contraceptive use. The effective interventions were conducted in Australia, Nepal, Pakistan, and the United States. Postpartum education about contraception led to more contraception use and fewer unplanned pregnancies. Short-term interventions were limited by self-reported outcomes or showing no effect for many comparisons. The longer-term programs were promising and not necessarily more costly than usual care. Health care providers can determine if 1 of these interventions suits their setting and level of resources. TARGET AUDIENCE: Obstetricians & Gynecologist, Family Physicians. LEARNING OBJECTIVES: After completing this educational activity, the participant should be better able to assess the importance of assessing delivery methods when examining intervention quality, evaluate the evidence from randomized trials on the effectiveness of postpartum education, and employ why additional research on postpartum education is needed for improving clinical practice. PMID- 20591203 TI - Pelvic congestion syndrome-associated pelvic pain: a systematic review of diagnosis and management. AB - To systematically evaluate the diagnosis and treatment of female pelvic congestion syndrome (PCS). We searched the PubMed database and relevant bibliographies for English-language studies published between January 1966 and May 2009 pertaining to diagnosis and treatment of female PCS-related pelvic pain. Treatment articles were restricted to those containing at least 4 subjects and a specified length of follow-up. Diagnostic test studies were included if they included subjects with and without pelvic pain. Two reviewers abstracted characteristics and outcomes from all controlled diagnostic studies and treatment papers. Six diagnostic and 22 treatment studies met entry criteria. Diagnostic method studies (pelvic venography, magnetic resonance imaging, or ultrasound) generally lacked appropriate reference standards, blinded assessors, or proven reliability. Treatment studies (using transvenous catheter embolization, surgical ligation, hysterectomy, or hormonal suppression) reporting ordinal outcomes found improvement from 24% to 100%; a similarly wide range of improvement was found with change in continuous rating of visual analogue scale pain scores (mean follow-up 4 months to 5.6 years). Both progestins and gonadotropin-releasing hormone agonists are effective in decreasing pain symptoms. The optimal diagnostic approach for PCS-related pelvic pain remains unclear, and controlled trials comparing medical and interventional treatments are urgently needed for PCS-associated pelvic pain. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to Compare different surgical treatments for pelvic congestion syndromes associated with pelvic pain syndromes. Estimate the relative severity of pelvic congestion in women using current venographic criteria. Choose between different diagnostic methods for characterizing pelvic venous blood flow and anatomy in women presenting with pelvic pain. PMID- 20591204 TI - Nicardipine for the treatment of severe hypertension in pregnancy: a review of the literature. AB - To evaluate the efficacy and safety of intravenous nicardipine for the treatment of severe hypertension in pregnancy. Articles were identified through electronic databases (Medline and Cochrane). No date or language restrictions were placed. Relevant citations were hand searched. The following search terms were used: pregnancy, severe hypertension and nicardipine. Patients included had chronic or gestational hypertension with or without marked proteinuria. Primary outcomes were reduction of systolic/diastolic and/or mean arterial pressure, time to target blood pressure, and severe maternal (hypotension, tachycardia) or severe fetal side effects (CTG abnormalities needing direct intervention). Five studies were found describing the use of nicardipine for treatment of severe hypertension in pregnancy. All studies were included in this review. One hundred forty-seven patients were treated. All patients had a significant reduction of both diastolic and systolic blood pressure. Treatment resulted in a 91% success rate in studies that defined success and 20% reduction of mean arterial blood pressure or systolic/diastolic blood pressure in 87%. Target blood pressure was reached within 23 minutes in 70% of the patients, 91% reached target blood pressure within 130 minutes. No severe maternal or fetal side effects were recorded. Nicardipine is a very effective therapy for treatment of severe hypertension in pregnancy and may be a better alternative to other available treatment options. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to evaluate the relative effectiveness of nicardipine for the treatment of severe hypertension in pregnancy. Compare the side effect profile of nicardipine to labetolol for the treatment of severe hypertension in pregnancy and calculate the appropriate dosing of nicardipine for the treatment of hypertension in pregnancy. PMID- 20591205 TI - Nutrition Research Reviews. Editorial. PMID- 20591206 TI - A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. AB - There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides-Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers. PMID- 20591207 TI - Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets. AB - Taurine (TAU) supplementation increases insulin secretion in response to high glucose concentrations in rodent islets. This effect is probably due to an increase in Ca2+ handling by the islet cells. Here, we investigated the possible involvement of the cholinergic/phospholipase C (PLC) and protein kinase (PK) A pathways in this process. Adult mice were fed with 2% TAU in drinking water for 30 d. The mice were killed and pancreatic islets isolated by the collagenase method. Islets from TAU-supplemented mice showed higher insulin secretion in the presence of 8.3 mm-glucose, 100 MUm-carbachol (Cch) and 1 mm-3-isobutyl-1-methyl xanthine (IBMX), respectively. The increase in insulin secretion in response to Cch in TAU islets was accompanied by a higher intracellular Ca2+ mobilisation and PLCbeta2 protein expression. The Ca2+ uptake was higher in TAU islets in the presence of 8.3 mm-glucose, but similar when the islets were challenged by glucose plus IBMX. TAU islets also showed an increase in the expression of PKAalpha protein. This protein may play a role in cation accumulation, since the amount of Ca2+ in these islets was significantly reduced by the PKA inhibitors: N [2-(p-bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H89) and PK inhibitor (6-22)-amide (PKI). In conclusion, TAU supplementation increases insulin secretion in response to glucose, favouring both influx and internal mobilisation of Ca2+, and these effects seem to involve the activation of both PLC-inositol 1,4,5-trisphosphate and cAMP-PKA pathways. PMID- 20591208 TI - Trends in dietary carbohydrate quality during puberty from 1988 to 2007: a cause for concern? AB - The extent to which the quality of dietary carbohydrates (CHO) changes throughout puberty is not known. We analysed trends in the quantity and quality of CHO intake among German adolescents by separately examining trends during puberty (pubertal trends) and trends in CHO intake from 1988 to 2007 (secular trends). Linear mixed-effects regression analyses were performed in 216 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study who had provided weighed 3 d dietary records at the onset of the pubertal growth spurt (defined by age at take-off) and over the subsequent 4 years. Over the course of puberty, CHO quality changed little: added sugar intake from beverages increased in girls (0.25 (se 0.12) % energy (% E)/year, P = 0.04) and added sugar intake from sweets decreased in both sexes (boys: - 0.22 (se 0.11) % E/year, P = 0.049; girls: - 0.20 (se 0.10) % E/year, P = 0.04). For both sexes, significant upward secular trends were observed for CHO (% E), glycaemic load (g/MJ) and added sugar intakes from sources other than sweets and soft drinks (% E), while absolute fibre intake (g/d) decreased (P <= 0.04). Concomitant increases in total added sugar intake (% E) and decreases in fibre and whole-grain densities (g/MJ) (P = 0.001-0.02) were confined to boys only. The quality of dietary CHO consumed by healthy German adolescents shows notable secular declines, but does not change markedly during puberty. Public health initiatives should be tailored to improve the overall quality of CHO nutrition. PMID- 20591209 TI - Influenza in animals. PMID- 20591210 TI - Perspectives on influenza evolution and the role of research. AB - Influenza is a highly contagious respiratory pathogen that continues to evolve and threaten both veterinary and human public health. Influenza A viruses are continually undergoing molecular changes through mutations, reassortment, and, in rare instances, recombination. While they generally cause benign enteric infection in their natural reservoir of wild aquatic birds, they can cause catastrophic and potentially lethal disease outbreaks in humans, domestic poultry, and pigs when they cross the host species barrier. The continuing circulation of highly pathogenic (HP) H5N1 influenza viruses in domestic poultry in parts of Eurasia and the emergence and global spread of pandemic H1N1 2009 are current examples of influenza evolution. The spread of both HP H5N1 and pandemic H1N1 to multiple hosts emphasizes the potential for continued evolution. In this review, we discuss the current understanding of influenza A virus structure and strategies of variation, with a specific focus on the HP H5N1 and pandemic H1N1 influenza viruses. Additionally, we attempt to identify the gaps in our knowledge of H5N1 and pandemic H1N1 influenza viruses. These gaps include (i) an understanding of the molecular determinants of influenza virus and the host that permit efficient transmissibility and pandemic potential, (ii) the urgent need for prospective surveillance in apparently healthy swine, (iii) the molecular determinants of high pathogenicity in poultry, pigs, and people, (iv) the genetic basis of host susceptibility, (v) antigenic variability, (vi) the use of vaccine to control influenza, (vii) the role of wild birds as the reservoir of highly pathogenic avian influenza, (viii) the problems with vaccines, (ix) seasonality, (x) co-infections, and (xi) anti-influenza drug resistance. Our failure to eradicate HP H5N1 globally and to explain why H5N1 does not transmit efficiently in humans while an H1N1 pandemic virus of swine origin spread globally in months are key examples that emphasize the critical need to bridge these knowledge gaps. Future directions in influenza research that will help us resolve each of the above-mentioned knowledge gaps include complete genomic and proteomic analysis of both the virus and the host with the prospect of designing new control strategies and the development of genetically resistant hosts. PMID- 20591211 TI - Avian influenza: our current understanding. AB - Avian influenza (AI) virus is one of the most important diseases of the poultry industry around the world. The virus has a broad host range in birds and mammals, although the natural reservoir is wild birds where it typically causes an asymptomatic to mild infection. The virus in poultry can cause a range of clinical diseases and is defined either as low pathogenic AI (LPAI) or highly pathogenic AI (HPAI) depending on the type of disease it causes in chickens. Viruses that replicate primarily on mucosal surfaces and cause mild disease with low mortality are termed LPAI. Viruses that replicate on mucosal surfaces and systemically and cause severe disease with a mortality rate of 75% or greater in experimentally infected chickens are referred to as HPAI. A virus that is highly pathogenic in chickens may infect but result in a completely different disease and replication pattern in other host species. Outbreaks of HPAI have been relatively uncommon around the world in the last 50 years and have had limited spread within a country or region with one major exception, Asian lineage H5N1 that was first identified in 1996. This lineage of virus has spread to over 60 countries and has become endemic in poultry in at least four countries. AI virus also represents a public health threat, with some infected humans having severe disease and with a high case fatality rate. AI remains a difficult disease to control because of the highly infectious nature of the virus and the interface of domestic and wild animals. A better understanding of the disease and its transmission is important for control. PMID- 20591212 TI - Avian biology, the human influence on global avian influenza transmission, and performing surveillance in wild birds. AB - This paper takes a closer look at three interrelated areas of study: avian host biology, the role of human activities in virus transmission, and the surveillance activities centered on avian influenza in wild birds. There are few ecosystems in which birds are not found. Correspondingly, avian influenza viruses are equally global in distribution, relying on competent avian hosts. The immune systems, annual cycles, feeding behaviors, and migration patterns of these hosts influence the ecology of the disease. Decreased biodiversity has also been linked to heightened disease transmission in several disease systems, and it is evident that active destruction and modification of wetland environments for human use is impacting avian populations drastically. Legal and illegal trade in wild birds present a significant risk for introduction and maintenance of exotic diseases. After the emergence of HPAI H5N1 in Hong Kong in 1996 and the ensuing geographic spread of outbreaks after 2003, both infected countries and those at risk of introduction began intensifying avian influenza surveillance efforts. Several techniques for sampling wild birds for influenza viruses have been applied. Benefits, problems, and biases exist for each method. The wild bird avian influenza surveillance programs taking place across the continents are now scaling back due to the rise of other spending priorities; hopefully the lessons learned from this work will be preserved and will inform future research and disease outbreak response priorities. PMID- 20591213 TI - Interspecies and intraspecies transmission of influenza A viruses: viral, host and environmental factors. AB - Influenza A viruses are enveloped viruses belonging to the family Orthomyxoviridae that encompasses four more genera: Influenza B, Influenza C, Isavirus and Thogotovirus. Type A viruses belong to the only genus that is highly infectious to a variety of mammalian and avian species. They are divided into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). So far, 16 HA and 9 NA subtypes have been identified worldwide, making a possible combination of 144 subtypes between both proteins. Generally, individual viruses are host-specific, however, interspecies transmission of influenza A viruses is not uncommon. All of the HA and NA subtypes have been isolated from wild birds; however, infections in humans and other mammalian species are limited to a few subtypes. The replication of individual influenza A virus in a specific host is dependent on many factors including, viral proteins, host system and environmental conditions. In this review, the key findings that contribute to the transmission of influenza A viruses amongst different species are summarized. PMID- 20591214 TI - Genome informatics of influenza A: from data sharing to shared analytical capabilities. AB - Emerging infectious diseases are critical issues of public health and the economic and social stability of nations. As demonstrated by the international response to the severe acute respiratory syndrome (SARS) and influenza A, rapid genomic sequencing is a crucial tool to understand diseases that occur at the interface of human and animal populations. However, our ability to make sense of sequence data lags behind our ability to acquire the data. The potential of sequence data on pathogens is not fully realized until raw data are translated into public health intelligence. Sequencing technologies have become highly mechanized. If the political will for data sharing remains strong, the frontier for progress in emerging infectious diseases will be in analysis of sequence data and translation of results into better public health science and policy. For example, applying analytical tools such as Supramap (http://supramap.osu.edu) to genomic data for pathogens, public health scientists can track specific mutations in pathogens that confer the ability to infect humans or resist drugs. The results produced by the Supramap application are compelling visualizations of pathogen lineages and features mapped into geographic information systems that can be used to test hypotheses and to follow the spread of diseases across geography and hosts and communicate the results to a wide audience. PMID- 20591215 TI - Comparative study on anti-tumor immune response of autologous cytokine-induced killer (CIK) cells, dendritic cells-CIK (DC-CIK), and semi-allogeneic DC-CIK. AB - BACKGROUND AND OBJECTIVE: Cytokine-induced killer (CIK) cells and autologous dendritic cells-CIK (DC-CIK) cells co-cultured with autologous dendritic cells (DCs) and CIK cells are commonly used for immunotherapy recently. We compared the anti-tumor immune response of CIK cells, autologous DC-CIK cells, and semi allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach. METHODS: Peripheral monocytes were isolated from patients with renal carcinoma, lung cancer, or maxillary squamous cell carcinoma and their healthy adult children. Isolated cells were cultured and induced as DCs and CIK cells in vitro. CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively, generating DC-CIK cells and semi-allogeneic DC-CIK cells. The anti-tumor activities of autologous CIK cells, autologous DC CIK cells, and semi-allogeneic DC-CIK cells were measured by LDH assay. Intracellular staining was used to test the secretion of cytokines. Flow cytometry was applied for detecting the phonotype changes of these three types of cells. Cell proliferation and cell apoptosis were detected by 5,6 carboxyfluorescein diacetate succinimidyl ester (CFSE) and Annexin V/PI respectively. RESULTS: Compared with autologous CIK cells and DC-CIK cells, semi allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN gamma secretion, reduced IL-4 secretion, increased the ratio of CD3(+)CD56(+) cells and CD3(+)CD8(+) cells, decreased the number of CD4(+)CD25(+) cells, promoted cell proliferation, and lessened cell apoptosis. CONCLUSIONS: Semi allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells. Our results provided experimental evidence for clinical application of DC-CIK cells. PMID- 20591216 TI - Correlations of P21-activated kinase 1 expression to clinicopathological features of gastric carcinoma and patients' prognosis. AB - BACKGROUND AND OBJECTIVE: Recent studies proved that P21-activated kinase 1 (PAK1) is highly expressed in many kinds of tumor and plays an important role in genesis, development, and metastasis of tumor. We aimed to detect the expression of PAK1 in gastric carcinoma and to analyze its relationship with clinicopathological features and prognosis of gastric carcinoma. METHODS: Tissue microarray and immunohistochemical staining were performed to detect PAK1 in paraffin specimens of 189 gastric carcinomas, 54 paracancer tissues, 40 lymph nodes and 30 healthy tissues. Clinicopathologic features and follow-up data of the patients were analyzed by the Chi2 test and the Kaplan-Meier method. RESULTS: Positive rate of PAK1 was 73.0% in gastric carcinoma, 57.4% in paracancer tissues and 23.3% in healthy controls (Chi2 = 29.364, P < 0.05). Expression of PAK1 was significantly correlated with tumor size, tumor differentiation, lymph node metastasis, Lauren classification and invasive depth (all P < 0.05). The positive rate of PAK1 was significantly higher in primary gastric carcinomas than in metastatic lymph nodes (75.0% vs. 52.5%, Chi2 = 4.381, P < 0.05). Survival analysis using the Kaplan-Meier method showed that the expression of PAK1 was a predictor for poor prognosis of the patients with gastric carcinoma (Chi2 = 6.857, P < 0.01). CONCLUSIONS: Expression of PAK1 is an early molecular event in the tumorigenesis of gastric carcinoma. It is also closely correlated the development of gastric carcinoma and the patients' prognosis. PMID- 20591217 TI - A novel sesquiterpene Hirsutanol A induces autophagical cell death in human hepatocellular carcinoma cells by increasing reactive oxygen species. AB - BACKGROUND AND OBJECTIVE: Hirsutanol A is a novel sesquiterpene compound purified from fungus chondrostereum sp in Sarcophyton tortuosum. Its pharmacologic effect has not been reported yet. This study aimed to investigate cytotoxic effect of Hirsutanol A on hepatocellular carcinoma (HCC) cells and its mechanism. METHODS: Hep3B cells were treated with different concentrations of Hirsutanol A. Cell proliferation was detected by MTT assay. The protein expression of LC3 was determined by Western blot. The generation of reactive oxygen species (ROS) was monitored by flow cytometry. RESULTS: Hirsutanol A significantly inhibited proliferation of Hep3B cells with 50% inhibition concentrations (IC50) of 14.54, 6.71, and 3.59 micromol/L when exposed to Hirsutanol A for 24, 48, and 72 h, respectively. Incubation of Hep3B cells with Hirsutanol A markedly increased the level of ROS and the autophagy marker MAP-LC3 conversion from type I to type II. Pre-incubation with an antioxidant N-acetyl cystein (NAC) decreased the level of ROS, and reduced MAP-LC3 I-II conversion, and suppressed cell death. Blocking autophagy with a specific autophagy inhibitor 3-methyladenine (3-MA), the cytotoxic effect of this compound was attenuated. CONCLUSION: Hirsutanol A has potent cytotoxic effect, and can induce autophagic cell death via increasing ROS production. PMID- 20591218 TI - Establishment and biological characteristics of oxaliplatin-resistant human colon cancer cell lines. AB - BACKGROUND AND OBJECTIVE: Chemotherapy is the main treatment for colon cancer, while multidrug-resistance is the main reason for chemotherapy failure and tumor relapse. This study was to establish two oxaliplatin-resistant colon cancer cell lines and evaluate their biological characteristics. METHODS: Oxaliplatin resistant colon cancer cell lines SW620/L-OHP and lovo/L-OHP were established in vitro by continuous exposure to oxaliplatin (L-OHP) of low and gradually increased concentration. Growth curve, cross-resistance and resistance index of the oxaliplatin-resistant cell lines to various anti-cancer agents were determined by CCK8 assay. The expressions of P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and MRP2 were detected by Western blot. Cell cycle distribution as well as the expression of CD133 and CD44 were measured by flow cytometry. RESULTS: It took 10 months to establish the SW620/L-OHP and LoVo/L-OHP cell lines with stable resistance to oxaliplatin. Cross-resistance to 5 fluorouracil, etoposide, cisplatin, vincristine and epirubicin but not to paclitaxel was observed. Longer doubling time, higher proportion of cells in G(0)/G(1) phase and lower proportion in G(2)/M phase were observed in the two oxaliplatin-resistant cell lines compared with their parental cell lines. The expression of MRP2 in the oxaliplatin-resistant cells was up-regulated, while those of P-gp and MRP1 had no significant change. CD133 was overexpressed while CD44 level remained unchanged in SW620/L-OHP and LoVo/L-OHP cells. CONCLUSIONS: SW620/L-OHP and LoVo/L-OHP cell lines show a typical and stably resistant phenotype and may be used as research models. PMID- 20591219 TI - The clinical value of adjuvant radiotherapy in patients with early stage breast cancer with 1 to 3 positive lymph nodes after mastectomy. AB - BACKGROUND AND OBJECTIVE: The role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-T2 tumors and 1-3 positive axillary nodes is still uncertain. This study investigated the value of PMRT for these patients. METHODS: In the retrospective data of 488 eligible patients, survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and the Cox proportional hazards model, respectively. RESULTS: The median observation time was 54 months. The 5- and 10 year locoregional recurrence-free survival (LRFS) rates were 90.8% and 86.9%, respectively. The 5- and 10-year disease-free survival (DFS) rates were 82.0% and 74.3%, respectively. The 5- and 10-year overall survival (OS) rates were 90.7% and 82.7%, respectively. For the 412 patients without PMRT, T2 classification, 2 3 positive nodes, and hormone (estrogen and progesterone) receptor-negative were risk factors for locoregional recurrence in the multivariate analysis. On the basis of these 3 risk factors, the group with 2-3 factors had a 10-year LRFS rate of 63.1% compared with 96.1% for the group with 0-1 factors (P < 0.001). For the group with 2-3 risk factors, LRFS and DFS were significantly improved by PMRT, with the 5- and 10-year LRFS rates without PMRT of 82.4% and 63.1%, respectively, and, with PMRT, of 98.1% at both 5 years and 10 years (P = 0.002). The 5- and 10 year DFS rates without PMRT were 72.0% and 57.6%, respectively, and, with PMRT, the 5- and 10-year DFS rates were 89.4% and 81.7%, respectively (P = 0.007). There was no significant difference in the 10-year OS rates between patients with and without PMRT. However, there is the potential benefit of 15.3% (87.1% vs. 71.8%, P = 0.072). Conversely, the group with 0-1 factors of PMRT had no effect on prognosis. CONCLUSIONS: In patients receiving mastectomy with T1-T2 breast cancer with 1-3 positive nodes, for the group with 2-3 risk factors, PMRT significantly improved LRFS and DFS and has potential benefit in OS. PMID- 20591220 TI - Low dosage 5-fluorouracil increases the transfection efficiency of Ad/VEGF-A in mouse lung carcinoma cell line LA795 and inhibits tumor growth. AB - BACKGROUND AND OBJECTIVE: Adenovirus vectors were widely used in gene therapy for tumors. We used adenovirus vector to transfer small interfering RNA (siRNA) against vascular epithelium growth factor A (VEGF-A) molecules to mouse lung adenoma LA795 cells and used low dose of chemotherapeutic drugs to further elevate the infection efficiency of adenovirus vector in and therapeutic effect of RNAi on tumor cells. METHODS: LA795 cells were infected by Ad/EGFP and treated with different dosages of gemcitabin, epirubicin, cisplatin, or 5-fluorouracil (5 FU). Cells were observed under fluorescence microscope continuously using green fluorescent protein (GFP) as the reporter gene. The percentage of GFP-positive cells and fluorescent intensity were tested by flow cytometry to determine optimum concentrations of drugs. Ad/siVEGF-A containing VEGF-A siRNA was constructed. Real-time PCR and ELISA were applied to measure the expression level of VEGF-A after LA795 cells were infected by Ad/siVEGF-A and treated with 5-FU. The combination of Ad/siVEGF-A and 5-FU was also applied in treating subcutaneous tumor in mice. RESULTS: Low dose of 5-FU elevated the Ad/EGFP infection in LA795 cells significantly, and also enhanced the effect of Ad/siVEGF-A in down regulating VEGF-A mRNA and protein levels in tumor cells. When used in tumor in vivo, the combination strategy repressed tumor growth effectively. CONCLUSION: Low dose of 5-FU can enhance the capability of adenovirus infecting tumor cells and promote the efficiency of gene therapy by adenovirus. PMID- 20591221 TI - Polymorphic catechol-O-methyltransferase gene, soy isoflavone intake and breast cancer in postmenopausal women: a case-control study. AB - BACKGROUND AND OBJECTIVE: Genetic polymorphism Val158Met of catechol-O methyltransferase (COMT) may contribute to estrogen-induced carcinogenesis of breast cancer. Soy isoflavones possesses chemical structure similar to endogenous estrogen and may promote the carcinogenesis of breast cancer. This study was to investigate the relationship between the polymorphism of COMT, soy isoflavones, and breast cancer in postmenopausal women. METHODS: In total, 176 patients newly diagnosed histopathologically with breast cancer were recruited from May 2007 to July 2009, and 176 age-matched cancer-free women as controls were selected from a community-based physical check-up population at the same period. The food frequency questionnaire was used to collect information on soy food intake. Allele-specific polymerase chain reaction (AS-PCR) was employed to analyze genetic polymorphism Val158Met of COMT. Adjusted odd ratios (aORs) and 95% confidence intervals (95% CI) were estimated by multivariable nonconditional logistic regression. RESULTS: The proportion of susceptible genotype (COMT-LL) in breast cancer patients was significantly higher than that in the controls. After adjusting selected risk factors, the aOR and 95% CI of COMT-LL were 3.14 (1.48 6.66) as compared with those of COMT-HH genotype. The intake of soy isoflavones had a negative correlation with breast cancer in a dose-dependent manner (Chi2 = 28.26, P < 0.001). The women with high intake of soy isoflavones (> or = 16.26 mg/d) and carrying susceptible genotype (COMT-LL), as compared with the women carrying the COMT-HH + COMT-HL genotypes and consuming low level of soy isoflavones (< 16.26 mg/d), had no significantly increased risk for breast cancer [ aOR (95% CI) = 1.66 (0.52-5.24)]. CONCLUSIONS: In postmenopausal women, carrying COMT-LL genotype may increase the risk for breast cancer, and soy isoflavones intake may protect them from breast cancer. But there may be no interaction between intake of soy isoflavones and COMT-LL genotype. PMID- 20591222 TI - Expression of Bmi-1 gene in esophageal carcinoma cell EC9706 and its effect on cell cycle, apoptosis and migration. AB - BACKGROUND AND OBJECTIVE: Previous studies have shown that Bmi-1 is overexpressed in a variety of tumors, suggesting that Bmi-1 plays an important role in tumorigenesis. In this study, we investigated the effect of Bim-1 siRNA on cell proliferation, cell cycle, cell apoptosis and migration of human esophageal carcinoma EC9706 cells, and explored its potential mechanisms. METHODS: Bmi-1 small interfering RNA (siRNA) was transferred into EC9706 cells. Then, cell proliferation was measured using cell counting kit-8 (CCK-8), cell cycle and cell apoptosis were analyzed by flow cytometry, cell migration ability was detected using Boyden chamber assay, and the mRNA and protein expression levels of Bmi-1, p16, Bcl-2, Bax, and MMP-2 were determined using real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. RESULTS: Bmi-1 siRNA treatment significantly inhibited the expression of Bmi-1 at both mRNA and protein levels in EC9706 cells. Cell proliferation rate decreased dramatically in the Bmi-1 siRNA treated group than in the untreated group and in the scrambled siRNA treated group (both P < 0.001). In Bmi-1 treated group, the percentage of cells at G(0)/G(1) stage was 71.93%, which was higher than that in the untreated group (47.36%) or scramble siRNA treated group (48.47%) (both P < 0.001). Early cell apoptosis rate also increased significantly in the Bmi-1 siRNA treated group (both 17.32%) than in the untreated group (2.61%) and in the scramble siRNA treated group (2.73%) (both P < 0.001). Further experiment suggested that downregulation of Bmi-1 led to less cell migration. In EC9706 cells transfected by Bmi-1 siRNA, the expression levels of p16 and Bax increased, while the expression level of Bcl-2 decreased. CONCLUSIONS: Bmi-1 downregulation in esophageal carcinoma cells inhibits cell proliferation, cell cycle, and cell migration, while increases cell apoptosis. These results suggest that Bmi-1 is a potential molecular target of treating esophageal cancer. PMID- 20591223 TI - TMSG-1 and its roles in tumor biology. AB - TMSG-1 is a newly discovered tumor metastasis suppressor gene, which plays important roles in promoting apoptosis and inhibiting invasion and metastasis of tumor cells. The inhibitory function of TMSG-1 in tumor cells may be related to vacuolar H+-ATPase and ceramide, but the underlying mechanism remains unknown. Studies on TMSG-1 are limited worldwide, and only a research group in Shanghai and our group have recently studied on it. As a new research field, the function of TMSG-1 remains to be explored. This review discusses the discovery of TMSG-1, structure of its encoded protein, its roles and possible mechanism in inhibiting tumor invasion and metastasis. PMID- 20591224 TI - Comparative study on imaging and pathological features of elastofibroma dorsi. AB - BACKGROUND AND OBJECTIVE: Elastofibroma dorsi has an extremely low incidence. At present, comparative study on imaging manifestations and pathologic findings of elastofibroma dorsi has not been reported in China. This study was to investigate clinical manifestations, computed tomography (CT) and magnetic resonance imaging (MRI) appearances, and pathologic features of elastofibroma dorsi and to improve preoperative imaging diagnosis of this disease. METHODS: The clinical manifestations, imaging findings, and pathologic appearances of 6 cases of elastofibroma dorsi were retrospectively analyzed and related literatures were reviewed. All patients were examined with MRI, and 4 of them were examined with CT scan. RESULTS: All patients were above 30 years old without obvious symptoms. The tumors presented as a lenticular soft-tissue mass in the deep subscapular region. The tumor's density on plain CT scan or signal intensity on MR T1 weighted image was approximately equal to that of muscle with some interlaced fat like areas within mass suppressed by fat-suppression MR sequences, which corresponded to dense collagen tissue and interspersed mature adipose tissue observed microscopically. CONCLUSIONS: CT and MRI can reflect the histological features of elastofibroma dorsi. On the basis of their imaging characteristics, a correct preoperative diagnosis of elastofibroma dorsi can easily be made. PMID- 20591225 TI - Hydroxyapatite and bFGF Coating of Detachable Coils for Endovascular Occlusion of Experimental Aneurysm. AB - SUMMARY: The purpose of this study was to evaluate the effect of hydroxyapatite (HAp) and fibroblast growth factor-basic (bFGF) coating on Guglielmi detachable coils (GDCs) in an experimental aneurysm model. A total of 18 aneurysms were experimentally made in the common carotid arteries of swine. Embolization was done on these aneurysms using standard GDCs and coated GDCs with HAp (GDC-HAp) and with bFGF (GDC-HAp-bFGF). The animals were then killed 14 days after embolization. The development of tissue scarring and coverage the aneurysm's orifice were evaluated macroscopically. No significant difference of volume ratio of the coils exited in each groups. Macroscopically, covering ratio of fibrous membrane at the neck of aneurysms were 88.3 +/- 14.7% in a group with GDC-HAp bFGF, while it were 26.7 +/- 15.3% in a group with standard GDC and it was 41.7 +/- 31.7% in a group with GDC-HAp. These results indicated that coating by hydroxyapatite and bFGF might facilitate a wound healing in an experimental aneurysm model. PMID- 20591226 TI - Editorial. PMID- 20591227 TI - Clinical and Angiographic Results of Intra-Aneurysmal Embolization for Cerebral Aneurysms and Histopathological Findings in an Aneurysm Treated with GDC. AB - SUMMARY: We describe follow-up clinical and angiographic results in patients with cerebral aneurysms treated with IDC or GDC. In 175 patients, 116 patients with ruptured aneurysm and 59 patients with non-ruptured aneurysm who underwent endovascular occlusion of aneurysms, there was no mortality and nine cases (4.7%) with morbidity in the periprocedural period. During follow up period, four cases (2.3%) experienced bleeding, and three cases (1.7%) experienced thrombo-embolic events. On the follow-up angiograms (median angiographic follow-up period 24.8 months), 12.5% of incompletely obliterated aneurysms exhibited progressive thrombosis, 20% remained unchanged and 67.5% showed aneurysmal recanalization or regrowth. Histological examination of a small ruptured A-com aneurysm treated seven months before harvesting, demonstrated that formation of an incomplete endothelium- lined layer of connective tissue at the orifice, and no complete fibrous obliteration of the aneurysm lumen could be detected, various amounts of unorganized clot were still present in the center of the aneurysm. Coil embolization is a safe treatment for cerebral aneurysms with a lower incidence of peri-procedural morbidity, wheareas follow-up results are less satisfactory in cases involving incompletely obliterated lesions. PMID- 20591228 TI - The Role of GDC Embolization as a Second Choice in the Treatment of Ruptured Cerebral Aneurysm. Retrospective Analysis from Mid-Term Outcome. AB - SUMMARY: We investigated the role of GDC embolization as a second choice for the treatment of ruptured cerebral aneurysm. From september 1997 to may 2001, 139 ruptured aneurysms out of 151 consecutive ruptured aneurysms transferred to our hospital were treated by clipping (first choice) or GDC embolization (second choice). Patient selection was decided by more than two neurosurgeons under the policy that GDC embolization is the second choice of treatment. The mid-term (longer than three months) outcome of both group was examined. One hundred and nineteen Ans (BA two, ICparaclinoid one, IC-PC or IC-Ach 36, IC-ant. Wall two, ACoA34, ACA six, MCA38) were treated by clipping (clipping group), 20 Ans (surgical difficulty; BA three, IC-paraclinoid three, VA dissection six, general complications; IC-PC two, IC-dissection one, ACoA four, VAPICA one) by GDC embolization (GDC group) within 24 hours after admission. SAH grade and GOS of each group were Gr1: 35&4, Gr2: 41&5, Gr3: 23&5, Gr4: 11&4, Gr5: 9&2, respectively, and GR: 79&14, MD: 8&3, SD: 11&0, VS: 8&0, D: 13&3 respectively. Good prognosis (better than MD) was gained in 73% of clipping group and 85% of GDC group. No rebleeding was seen in GDC group. GDC embolization for the cases with surgical difficulty or general complication raised the overall outcome. GDC embolization would be suitable for IC-paraclinoid Ans, BA-VA Ans, and ruptured VA dissections. Because of the good clinical outcome gained in the GDC group, GDC treatment would be the first choice of treatment for such aneurysms as geometrically suitable for coiling. PMID- 20591229 TI - Angiographic Follow-up of Embolization Using Guglielmi Detachable Coils for Cerebral Aneurysms. AB - SUMMARY: The purpose of this study is to evaluate the mid or long-term angiographical stability of Guglielmi Detachable Coils (GDC) after embolization for cerebral aneurysms. Between march 1997 and november 2001, 164 aneurysms, including 116 ruptured and 48 unruptured aneurysms, were treated using GDC at Mito National Hospital. Cerebral angiograms over one month after embolization were obtained in 111 aneurysms, including 71 ruptured and 40 unruptured aneurysms.At the time of initial GDC embolization of the 71 ruptured aneurysms, complete occlusion was achieved in 31 aneurysms, neck remnant in 18 aneurysms, and body filling in 22 aneurysms. Morphological changes were observed in 26 aneurysms (37%) in follow-up. Progressive thrombosis was obtained in 12 out of 71 aneurysms, no changes were shown in 45, and recanalizations occurred in 14. In the initial embolization of the 40 unruptured aneurysms, complete occlusion was achieved in 15 aneurysms, neck remnant in five and body filling in 20 aneurysms respectively. Morphological changes were observed in 12 aneurysms (30%), in which 12 aneurysms showed progressive thrombosis and 28 aneurysms were unchanged. There were significant differences of the longterm angiographical stability between ruptured and unruptured aneurysms. Rigorous follow-up angiography is mandatory when complete aneurysm occlusion is not achieved in ruptured aneurysms. PMID- 20591230 TI - Treatment Strategy for Cerebral Aneurysms Based on the Evidence of the Efficacy of GDC Embolization. AB - SUMMARY: The authors reviewed 531 patients with cerebral aneurysms treated with Guglielmi detachable coils (GDCs) over 5 years to clarify both the advantages and disadvantages of embolization based on the evidence of complications by aneurysm profile. There were 52 technical complications, 25 of which resulted in unfavorable patient outcomes. Intraoperative rupture, the most serious complication exacerbating the patient's condition, occurred in 19 patients, 4 of whom expired. All of these aneurysms were very small and were mostly located in the AcomA and PICA portions. Thirteen patients encountered thromboembolic complications, 6 of whom were elderly with acute ruptured aneurysms at MCA and the tip of BA. For large or giant aneurysms manifesting the mass effect, particularly those in the ICA-C2 portion compressing the optic nerve, the saccular packing did little to ameliorate the symptoms, and subsequent surgical or endovascular trapping was needed. Therefore, saccular embolization of endovascularly difficult, very small AcomA aneurysms and large C2 aneurysm with visual symptoms should be used sparingly based on a risk-benefit assessment. PMID- 20591231 TI - Post-mortem pathological examination of two patients after intraaneurysmal embolization using guglielmi detachable coils. AB - SUMMARY: We report the histological findings in two patients treated using Guglielmi detachable coils with almost complete occlusion of the aneurysms.Autopsies of these patients were performed one week and one year after GDC embolization respectively. In one aneurysm that was obtained at autopsy one week after embolization, the histological findings revealed coils and an unorganized thrombus-filled aneurysm sac; an incomplete cell-lining on the luminal side of fibrin thrombi in the region of the neck of the aneurysm was recognized. In the other aneurysm in which autopsy was performed one year after embolization, an organized fibrous tissue at the margin of the aneurysmal wall and vascular granulation tissue at the center of the aneurysm were observed. There is a single layer of endothelium covering fibrous tissue in the neck of the aneurysm. We discuss the healing process after GDC treatment. PMID- 20591232 TI - Endovascular surgery for intracranial aneurysm. Histopathological analysis after embolization using balloon or coil. AB - SUMMARY: Recently, endovascular surgery became common approach for management of intracranial aneurysms. Though its efficacy, this approach is still new and under development. Here, we report our clinical experience in patients treated with two methods - balloon or Gugliemi detachable coil. In addition, to understand better the mechanisms underlying postoperative complications, we studied them in histopathological specimens of patients and in a model of experimental aneurysm. From our data we conclude that choice of appropriate therapeutic method should respect specific conditions of patients as well as of facility. Careful postoperative studies including examination of intravascular surface by endovascular scope examination would be useful for prediction of possible complications. PMID- 20591233 TI - Histological evaluation of endothelial reactions after endovascular coil embolization for intracranial aneurysm. Clinical and experimental studies and review of the literature. AB - SUMMARY: The purpose of this study was to evaluate the role of the endothelial cell reaction after endovascular coil embolization for the treatment of intracranial aneurysms. A scanning electron microscopic (SEM) study of the platinum coil, embolized into a middle cerebral aneurysm in a 35-year-old woman and subsequently removed surgically eight months later, revealed no endothelial coverage on the coil. This finding prompted us to perform experimental studies. In the first in vitro study, endothelial cells from gerbil brain microvessels and canine carotid arteries were co-cultured with either bare-form platinum coils or type-1 collagen-coated coils for up to three weeks, and the endothelial cell population on the coils was ascertained. In the second in vivo study, platinum coils coated with type-1 collagen were delivered endovascularly into canine carotid arteries, while the contralateral side was treated with bare-form coils, and endothelialization over the coil was investigated. SEM studies revealed that no endothelial cells, either from gerbil brain microvessels or from canine carotid artery, were found on the uncoated coils, whereas gerbil endothelial cells began to proliferate on the collagen-coated coils in three days, covering extensively in one week and reaching confluence in two weeks in vitro. The in vivo canine study demonstrated that bare-form platinum coils did not show endothelial coverage until two weeks, but endothelial cells proliferated directly on the collagen-coated coils in three days, and coils were completely covered in two weeks. These results supported the SEM study of our case and several human histopathological reports in the literature in that endothelial cell coverage in the orifice of the intracranial aneurysm is exceptional after endovascular treatment. But if some extracellular matrix, like collagen in our study, is prepared, coverage could be possible, as is seen in a few human cases. Biological modification of the platinum coils, such as collagen coating, is awaited for the better long-term results of endovascular coil embolization without recanalization of the treated intracranial aneurysms. PMID- 20591234 TI - Treatment strategy for aneurysms of the posterior cerebral artery. AB - SUMMARY: The authors carried out a retrospective review of the records of 12 patients with aneurysms of the posterior cerebral artery (PCA). Four were asymptomatic, 1 presented with a mass effect, and 7 with a subarachnoid haemorrhage (SAH). Of the 7 ruptured aneurysms, 3 were embolized and 2 were clipped. However, 2 patients died from rebleeding before any treatment. Of the 5 unruptured aneurysms, 1 was embolized with coils but the remaining 4 have been conservatively observed. No aneurysms have ruptured during the follow-up period, and 3 have thrombosed spontaneously. According to our results, the PCA aneurysms should be treated aggressively in the early phase. Although the preservation of the anatomical integrity of the PCA should naturally be one of the prime objectives, PCA occlusion may sometimes be inevitable when treating large or fusiform aneurysms. On the other hand, conservative therapy is one of the options for the treatment of incidentally encountered unruptured ones, because these have the possibility of spontaneous thrombosis. PMID- 20591235 TI - Symptomatic cavernous internal carotid artery aneurysms treated with detachable coils. AB - SUMMARY: We reviewed the cranial nerve dysfunctions of eight patients with symptomatic cavernous internal carotid (CSIC) aneurysms treated by endovascular intraaneurysmal occlusion. Aneurysms were classified into three types according to their location and direction of growth. Anterior type aneurysms, which involved anterior bend of CSIC represented third nerve dysfunction. Posterior type aneurysms, which located posterior bend of CSIC preferred to affect sixth nerve function. CSIC aneurysms that extended over the both bends had total ophthalmoplegia. All patients responded to endovascular treatment, though partial resolution was recorded in the case of upward gaze or lateral gaze impairment. Endovascular treatment with detachable coils offers an excellent alternative with acceptable risks of morbidity. PMID- 20591236 TI - Clinical results and pathological findings of stent-assisted coil embolization for basilar artery trunk dissecting aneurysms. AB - SUMMARY: Stent-assisted coil embolization is a new method for treating dissecting or fusiform aneurysm, especially the aneurysms arising from the basilar artery trunk or dominant vertebral artery. At present, this technique is considered as an effective treatment option to obliterate such aneurysm keeping the parent artery patent. Several authors reported the effectiveness and excellent radiological result of this treatment, but fewer reports focus on the limitations of this technique. We treated two patients with a basilar artery trunk dissecting aneurysm with this technique. Transient ischemic symptoms were observed in one patient and haemorrhagic and thromboembolic complications were observed the other.We lost the latter patient due to postoperative complications, and the pathological finding was achieved by autopsy. We report the clinical and pathological findings in the two cases and investigate the efficacy and limitations of this technique. PMID- 20591237 TI - Radiological and pathological changes in the sinus of an experimental arteriovenous fistula of the rat. AB - SUMMARY: The object of this study is to evaluate the radiological and pathological changes in the sinus of an experimental arteriovenous fistula of the rat. Twenty-five male Sprague-Dawley rats, including two control rats, were used for this study. A venous hypertension model in the transverse sinus was induced by means of anastomosis of a common carotid artery (CCA) to the ipsilateral external jugular vein (EJV). Rats were sacrificed 11 to 42 weeks after the procedure, then histopathological and immunohistopathological examinations were performed for the resected transverse sinus. Follow-up angiography was performed two to three weeks after the anastomosis in every case, and five months later in two rats. Patency of the anastomosed portion was confirmed in 12 of the 23 anastomosed rats. An ipsilateral carotid angiogram demonstrated a highflow arteriovenous (AV) shunt from the CCA to the sigmoid-to-transverse sinus and draining into the contralateral juglar vein. A contralateral angiogram displayed a steal phenomenon via the communicating artery. Histopathologically, the vein of the anastomosed portion and the transverse sinus were markedly dilated in with cases. There was a thickening the connecting tissue and a proliferation of fibroblast in four (50%) of the eight cases. Thrombus formation in the transverse sinus was found in one case. VEGF stained strongly in the endothelial hypertrophied area and in fibrous connective tissue around the transverse sinus compared to the control sinuses. Our results from this long-term observation of the radiological and pathological changes in the sinus exposed to hypertension resembled the clinical findings of a dural AV fistula. PMID- 20591238 TI - Experimental polyvinyl alcohol core coil for a drug delivery system. AB - SUMMARY: We developed a new type of coil with a polyvinyl alcohol core (PVA-core coil) to absorb and release various types of biologically active materials, for the endovascular treatment of intracranial aneurysms. A 10 mm segment of the PVA core coil was used in this study. PVAcore coils were immersed in basic fibroblast growth factor (b-FGF) solution. The PVA-core coil, which absorbed b-FGF in the PVA core, was named FGF-core coil. This coil gradually released b-FGF in the solution without b-FGF. In vitro study, FGF-core coils, PVA-core coils and unmodified coils were cultured with fibroblasts (NIH3T3) respectively and their surface was observed with scanning electron microscopy (SEM). In vivo study, each coils were inserted into the rat common carotid artery. Rats were sacrificed and the arterial lumen were histologically examined 14 days and 28 days after coil implantation. Electron microscopy findings demonstrated remarkable cellular adhesion to the surface of the FGF-core coils, while no adhesion to the surface of the PVA-core coils and unmodified coils was found. Histologically, remarkable cellular proliferation and wall thickness like neointimal hyperplasia was demonstrated in the implanted common carotid artery of the FGF-core coil group at 14 days and 28 days. On the other hand, these changes did not occur in PVA-core coil group and unmodified coil group.We suggest that FGF-core coils may be effective to induce fibrotic changes inside cerebral aneurysms. PMID- 20591239 TI - Intra-arterial Chemotherapy for Malignant Tumors of Head and Neck Region Using Three Types of Modified Injection Method. AB - SUMMARY: Relatively higher infusion rate in the intra-arterial chemotherapy (IA chemotherapy) could induce the higher concentration and the more sufficient distribution of chemotherapeutic agents on tumors. To get the relatively higher infusion rate in IA chemotherapy, we used three types of injection method: high flow injection, high-dose injection with detoxification and flowcontrolled injection method for the treatment of malignant brain tumors, skull base tumors and head and neck tumors. Between January 1997 and October 2001, twenty-seven patients (mean age 61 y.o.) with supratentorial glioblastoma (4 cases), supratentorial anaplastic astrocytoma (1), CNS lymphoma (2), matastatic skull base tumors (3), and neck tumors (15 squamous cell carcinoma, 1 malignant melanoma and 1 neuroblastoma) received our three types of IA chemotherapy. Sixty- five consecutive procedures were performed. Conventional radiation therapy and/or surgical removal were performed in some of these patients. The median follow-up period was 10 months ranging 2 to 56 months. Fifteen (55.6%) and 6 (22.2%) of 27 patients achieved complete response (CR) and partial response (PR) respectively after initial treatment [CR+PR: 21 (77.8%)]. All responded patients showed clinical improvement. The response rate declined to 55.6% at the end of follow-up period. Eighteen patients are still alive and 15 of them show no evidence of local recurrence. The median post treatment survival was 12 months. There was no serious complication except transient nausea in 4 of 27 (14%) patients, vertigo and granulocytopenia in 1 each (3%) of 27 patients. Our modified IA chemotherapy has provided favorable clinical and radiological results without technical difficulties and serious complications. PMID- 20591240 TI - Correlation between Haemorrhagic Complications and CT Findings before and after Intra-arterial Reperfusion Therapy for Acute Middle Cerebral Artery Occlusion. AB - SUMMARY: The purpose of this study was to investigate whether haemorrhagic complications can be predicted by evaluating CT findings before and after intra arterial reperfusion therapy for acute middle cerebral artery (MCA) occlusion. Pretherapeutic early CT signs within three hours after onset and post-therapeutic contrast extravasation were evaluated in 61 patients treated within six hours after onset. Early CT signs were evaluated in the deep (obscuration of the margin of the lentiform nucleus and loss of the insular ribbon) and superficial MCA territories (cortical effacement). Haemorrhagic transformations were seen in 39.3% of patients, 54.2% of them had both pre-therapeutic early CT signs and post therapeutic contrast extravasation. Obscuration of the entire lentiform nucleus and the presence of contrast extravasation were reliable predictors for haemorrhagic transformations, and cortical effacement had also a tendency to be associated with haemorrhage. Absence of early CT signs did not always result in the absence of haemorrhagic transformations and 37.5% of haemorrhage occurred in the presumed normal area without early CT signs. On the other hand, absence of post-therapeutic contrast extravasation was a reliable negative predictor for intraparenchymal haematoma. PMID- 20591241 TI - Transcranial Doppler enhanced thrombolysis for embolic occlusion of major cerebral arteries. AB - SUMMARY: For the treatment of 11 patients with hyperacute embolic occlusion of major cerebral arteries (ten with occlusion of middle cerebral artery and one with occlusion of basilar artery), TCDenhanced thrombolysis (TCDET) was performed in combination with ultrasound irradiation, using diagnostic transcranial Doppler (TCD) (TC2-64B: 2MHz, 100mW/cm(2), pulsed wave) (TCDET group), and the effectiveness of this procedure was compared with that of local intra-arterial fibrinolysis (LIF) in 45 patients with embolic occlusion of the middle cerebral artery (LIF group). Regarding dose of TPA, the LIF group used 1046.7 +/- 607.8 units and the TCDET group 700.0 +/- 431.3 units (p < 0.05). Regarding time technically required to attain recanalization, the LIF group required 68.2 minutes, and the TCDET group 28.6 minutes. A good outcome was noted in 60.8% of the LIF group and 64% of the TCDET group. Haemorrhagic transformation was observed in 7.8% of the LIF group and in 0% of the TCDET group. No complications due to TCD irradiation were observed in the TCDET group. These findings suggest that TCDET can be an effective method of achieving recanalization. PMID- 20591242 TI - Clinical results of stenting for cervical internal carotid stenoses. AB - SUMMARY: Total 89 patients with cervical ICA stenosis were treated by stenting. In 74 cases of stenting, we used our blocking balloon systems to prevent distal embolism. The morbidity and the mortality rate was 4.5% and 0%, respectively.Two(3%) of 74 cases showed distal embolism when blocking balloon catheter systems(BBCS) were used, while distal embolism occurred in four (27%) of 15 cases of stenting without BBCS. On diffusion- weighted MRI (DWI), hyperintense areas were detected in seven (47%) of 15 lesions when we used BBCS only during postdilatation. On the other hand, use of BBCS during predilatation as well as postdilatation reduced hyperintense areas on DWI, which were detected in three (25%) of 12 patients. Our blocking balloon catheter system is a useful device to reduce the risk of distal embolism, especially when we use it during not only postdilatation but predilatation. PMID- 20591243 TI - Stenting of extracranial carotid artery stenosis. AB - SUMMARY: The purpose of this study is to evaluate our cases of cervical internal carotid artery stenosis for safty stenting.We investigate the preoperative internal carotid artery stenosis using by integrated backscatter (IBS) method of ultra sonography, comparing with the thirty five surgical specimens as to their nature, histological structure, thickness of fibrous cap. We choose the protection method according to plaque structure, and placed Easy-Wall stent or Smart stent after prePTA. We added post PTA according to the extent of expansion and IVUS findings. Calibrated IBS = IBS value (ROI) /intinal IBS value of 'bleeding', 'lipid', 'thrombus', 'fiber', 'hyalinization' were -27.5, -22.5, 15.2, -11.1, +2.1. That of the thin fibrous cap were -10.9*, that of thic fibrous cap were -2.4 (*p < 0.001). There was a good coleration between the extent of expansion and expected histological findings. All conplications were two cases of small cerebral infarction and a case of bleeding from the complicated lung cancer. The protection at prePTA lead to no comploications in case of acute cerebral infarctions. It is very important to check the histological specimen carefully for safty stenting. PMID- 20591244 TI - Staged carotid stenting and carotid endarterectomy for bilateral internal carotid artery stenosis. Preliminary experience. AB - SUMMARY: The purpose of this study was to evaluate the efficacy and safety of staged carotid stenting (CS) and carotid endarterectomy (CEA) for bilateral internal carotid artery stenosis. With this strategy, initial carotid stenting was performed for the high grade carotid stenosis to reduce the risk of subsequent CEA. Eight patients were treated with staged CS and CEA; CS for asymptomatic side followed by CEA for symptomatic side. Sufficient revascularization was obtained in all procedures but one CS procedure. Two minor stroke caused by distal embolism occurred during the perioperative period of CS. Postprocedural persistent hypotension was observed in one CS procedure. The mean interval between CS and CEA was 19.8 days. In conclusion, although our strategy has some advantages such as avoidance of bilateral cranial nerve palsy and shorter admission period over staged CEA, relatively high complication rate was noted at the first CS without any stroke morbidity post CEA. Our preliminary result showed that further reduction of periprocedural complication rate at the initial stenting is mandatory for this approach justified. PMID- 20591245 TI - Coil retrieval following embolization of cerebral aneurysms. AB - SUMMARY: Failed coil embolization of cerebral aneurysms may be occasionally followed by direct surgical treatment. We had 5 patients who underwent coil retrieval and surgical clipping after coil embolization because of periprocedural complications. The patients, ranging in age from 40 to 71, had wide-neck aneurysms located at the anterior communicating artery (AcomA) in 3 patients, the middle cerebral artery (MCA) in 1, and the internal carotidophthalmic artery (IC Ophthalmic) in 1. They were embolized with Guglielmi detachable coils (GDCs), which had to be retrieved within 8 days because of coil protrusion and migration in 3 patients, aneurysm rupture in 1, and increased mass effect due to coil compaction in 1. Coils were successfully removed with aneurysmotomy or arteriotomy under temporary trapping, aneurysms were then clipped or trapped. Three patients had a good outcome, but one suffered permanent visual disturbance and the other had a motor deficit. Our study revealed that a small AcomA aneurysm had a high risk of complication in a case of complex anatomy of the AcomA-A1-A2 complex with its difficult access. In addition, insufficient packing of the inflow zone in a large and symptomatic aneurysm may cause coil compaction and regrow with increasing mass effect. The indication and treatment strategy for these aneurysms should be carefully determined. PMID- 20591246 TI - Complications and Their Management During NBCA Embolization of Craniospinal Lesions. AB - SUMMARY: Technical complications during embolization of craniospinal lesions using NBCA may be classified as nonspecific catheterization-related or specific embolization-related. Catheterization- related complications include vessel injuries such as spasm, dissection or perforation, catheter injuries and thrombus formation. Embolization- related complications include occlusion of normal territories, migration of the embolic material to the venous side, and catheter gluing to the vessel wall. Causes, prevention and management of each complication are discussed with presentation of demonstrative cases. PMID- 20591247 TI - Complications associated with stenting for cerebral arteries. AB - SUMMARY: We have experienced total 116 stenting for 102 of cranio-cephalic arteries and 14 of intracranial arteries including occlusive cerebrovascular diseases, aneurysms, and fistulas.Ten complications were encountered. Three were ischemic complication, four stent migration, two restenosis, and one aneurysmal perforation during coiling across the stent strut. The mechanism and preventive method of these complications were discussed in this paper. PMID- 20591249 TI - Vasculogenesis and Angiogenesis: Molecular and Cellular Controls. Part 2: Interactions between Cell and Extracellular Environment. AB - SUMMARY: Angiogenesis, defined as a new blood vessel formation from a pre existing vessel, is initiated by angiogenic growth factors and their receptors that induce endothelial cell migration and proliferation. Extracellular proteolysis is essential for deassembly and reassembly of endothelial cells to their environmental matrix. The aim of this review is to update data on the role of the coagulation and fibrinolysis system, metalloproteinases and adhesion molecules during this step of angiogenesis. PMID- 20591248 TI - Vasculogenesis and angiogenesis: molecular and cellular controls. Part 1: growth factors. AB - SUMMARY: Angiogenesis characterizes embryonic development, but also occurs in adulthood in physiological situations such as adaptation to muscle exercise, and in pathological conditions like cancer. Major advances have been made in understanding the molecular mechanisms responsible for vasculogenesis and angiogenesis, largely due to the use of "knock-out mice", i.e. mice in which the gene coding for the protein under investigation has been inactivated. Interestingly, the same growth factors and their receptors are equally involved in the different aspects of vasculogenesis and angiogenesis during development and in adulthood. This review aims to describe in detail their respective roles and how interactions between them lead to a newly formed vessel. PMID- 20591250 TI - Glubran 2((r)):a new acrylic glue for neuroradiological endovascular use: a complementary histological study. AB - SUMMARY: Two Landrace Large White swine underwent angiography by the femoral route. In both cases, the superior left renal artery was embolized by injection of 2 ml of Glubran 2((R)), diluted with Lipiodol 1:1 thereby excluding the superior left kidney poles from blood flow. During the follow-up period, neither pig presented any clinical symptom correlated to the embolization procedure. Case 1 was sacrificed after 30 days and case 2 after 60 days. Macroscopic and microscopic analysis was performed in both animals. Long-term follow-up of the two cases after endovascular injection of Glubran 2((R)) showed that the embolization procedure was well-tolerated by the swine in terms of clinical symptoms and histological findings. Arterial occlusion was stable and a reasonable quantity of scar tissue appeared between 30 and 60 days, surrounding the ischaemic tissue. This follow-up experimental study offers further evidence that Glubran 2((R)) is a safe embolizing material for human use as far as its chemical activity is concerned. PMID- 20591252 TI - Brain and Spine AVMs, Vein of Galen Malformation. Treatments and Embryological Considerations. PMID- 20591251 TI - Stent Assisted Coil Embolization: the Treatment of Wide-necked, Dissecting, and Fusiform Aneurysms. AB - SUMMARY: Stent assisted coil embolization is a useful therapeutic modality for wide-necked and geometrically difficult aneurysms, as the stent provide a buttress that allows for coil deposition while preventing coil haerniation into the parent vessel lumen, and placement of an endovascular stent within the parent artery across the aneurysm neck may divert the blood from the aneurysm inflow tract and promote intra-aneurysm stasis and thrombosis.We report herein a 3 patients treated with endovascular stent-assisted coil embolization for symptomatic or enlarging wide-necked, dissecting, and fusiform aneurysms of the carotid and vertebrobasilar arteries. One patient had intracranial mass effect, the second had subarachnoid haemorrhage, and the third had angiographic evidence of enlarging aneurysm. The aneurysm was located in the petrous segment of internal carotid artery in one patient and in the intracranial vertebral artery in the other two patients. For all patients, we used balloon expandable stent (such as GFX, S-670) in this technique. Complete obliteration of the aneurysms could be achieved in all cases, with preservation of distal circulation. PMID- 20591253 TI - Intraarterial Thrombolysis with r-tPA for Treatment of Anterior Circulation Acute Ischemic Stroke. Technical and Clinical Results. AB - SUMMARY: To investigate factors effecting the safety and recanalization efficacy of local intraarterial (IA) recombinant tissue plasminogen activator (r-tPA) delivery in patients with acute ischemic stroke. Eleven patients with anterior circulation acute ischemic stroke were treated. The neurological status of the patients were graded with the Glasgow Coma Scale (GCS) and National Institute of Health Stroke Scale (NIHSS). All patients underwent a computed tomography (CT) examination at admission. In addition four patients had diffusion-weighted and one patient had a perfusion magnetic resonance (MR) examinations. Patients were treated within six hours from stroke onset. Immediate, six hours, and 24 hours follow-up CT examinations were performed in order to evaluate the haemorrhagic complications and the extent of the ischemic area. The Rankin Scale (RS) was used as an outcome measure. Two of the 11 patients had carotid "T" occlusion (CTO), nine had middle cerebral artery (MCA) main trunk occlusion. Four patients had symptomatic haemorrhage with a large haematoma rupturing into the ventricles and subarachnoid space. Of these, three patients died within 24 hours. The remaining seven patients had asymptomatic haematomas that were smaller compared to symptomatic ones, and showed regression in size and density on follow-up CTs. At third month five patients had a good outcome and three patients had a poor outcome. In acute ischemic stroke, local IA thrombolysis is a feasible treatment when you select the right patient. Haemorrhage rate does not seem to exceed that occuring in the natural history of the disease and in other treatment modalities. PMID- 20591254 TI - Transarterial Wedged-catheter, Flow-arrest, N-butyl Cyanoacrylate Embolization of Three Dural Arteriovenous Fistulae in a Single Patient. AB - SUMMARY: The pathogenesis of dural arteriovenous fistulas (DAVFs) is currently unknown, with multiple DAVFs being rare. For patients with limited venous access secondary to sinus thrombosis, or for patients where parent sinus occlusion would not be tolerated, transvenous embolization may not be possible and other treatment methods must be considered. A 69-year-old female patient with a two year history of progressive headaches, memory loss, and unsteady gait underwent cerebral angiography that revealed three separate DAVFs with congested cortical venous drainage overlying both frontal lobes. Using an application of a transarterial wedged-catheter, flow-arrest technique, N-butyl cyanoacrylate was deposited across all three pathologic arteriovenous connections providing a definitive cure. Transarterial NBCA embolization may provide curative treatment of DAVFs, and is of particular utility in situations where access to the draining venous structures is limited. PMID- 20591255 TI - Treatment of carotid cavernous fistula secondary to rupture of a giant intracavernous carotid aneurysm. Transarterial coiling of aneurysm and carotid compression. A case report. AB - SUMMARY: Carotid cavernous fistula secondary to ruptured giant intracavernous aneurysm of the internal carotid artery is rare.We report a case of direct carotid cavernous fistula secondary to rupture of a giant intracavernous ICA aneurysm. The presence of mirror or twin aneurysms of bilateral ophthalmic arteries raises therapeutic challenge. Coiling of the intracavernous aneurysm could partially occlude the fistula. Complete closure of the fistula was facilitated by secondary carotid compression. PMID- 20591256 TI - Management of a direct carotid cavernous fistula caused by rupture of a cavernous aneurysm previously embolized with coils. AB - SUMMARY: The development of a high-flow carotid-cavernous fistula from the rupture of a large cavernous aneurysm successfully embolized by coils is rare. A 50-year-old male patient developed a high-flow carotid-cavernous fistula 48 hours after successful coiling of a large left cavernous aneurysm, presumably due to rupture of a focal dissection at or close to the neck of the aneurysm. He initially responded to daily selfcompression of the left common carotid artery, but the fistula recurred. After failing to approach the fistula site via transvenous route, balloon trapping of the internal carotid artery was planned. Prior to its placement for functional occlusion test, the detachable balloon slipped into the fistula site and occluded it. It was thereafter detached in this position. The sequence of events, a large cavernous aneurysm spontaneous ruptured after coiling, suggested dissecting process or disease.We address in the report the complexity of the endovascular management of this rare association. PMID- 20591257 TI - Carotid artery stenting to prevent stroke in a patient with bilateral extracranial internal carotid dissection and vasospasm following rupture of an intracranial aneurysm. AB - SUMMARY: The stenting of carotid dissection has been described for the prevention of cerebral ischemia in patients who remain symptomatic despite therapeutic anticoagulation, in those who present contraindications for anticoagulation therapy, or who present a local or extensive stenosis, with an associated pseudoaneurysm. We here report a case associating a high clinical grade aneurysmal rupture with a bilateral extracranial carotid dissection. Because of the haemodynamic risk due to the acute bilateral stenosis-induced dissection and the occurrence of a vasospasm, the carotid dissections were treated with self expendable stents. PMID- 20591258 TI - Retinal embolization and cerebellar asymptomatic embolization after carotid stenting using distal balloon protection. A case report. AB - SUMMARY: We describe a rare case of having both symptomatic ipsilateral retinal embolization and asymptomatic cerebellar embolization occurring after carotid stenting with use of distal protect device. In this case, external carotid angiograms revealed accessory meningeal arteryophthalmic artery and occipital artery-vertebral artery anastomoses. This case suggested that the protection for external carotid artery should be considered during carotid stenting to avoid retinal embolization and cerebellar or cerebral embolization in cases showing angiographical anastomoses between external carotid artery and ophthalmic artery or intracranial arteries. PMID- 20591259 TI - Intracranial Haemorrhage Probably Due to an Angiographically Occult AVM after Carotid Stenting. A Case Report. AB - SUMMARY: Angiographically occult vascular malformations refer to cerebrovascular malformations that are not demonstrable on technically satisfactory cerebral angiography. Authors herein present a very unusual intracranial bleeding complication related to an angiographically occult vascular malformation after extracranial carotid artery stenting procedure. A 52-year-old male patient admitted to the hospital with 2 episodes of amaurosis fugax in the left eye. Cervical carotid angiography and bilateral carotid Doppler ultrasonography revealed a 98% stenosis of the left internal carotid artery just distal to the bifurcation. Post-stenting control cervical carotid angiography revealed neither any residual stenosis nor a developmental venous anomaly. The patient developed left pupil dilatation with loss of consciousness two hours after the neurovascular intervention. Emergent cranial CT showed acute subdural haematoma, intracerebral and subarachnoid haemorrhage with massive midline shift. He underwent an emergent craniotomy with left temporal lobectomy. Abnormal cortical vascular structures with prominent engorgement were remarkable over the posterior temporal cortex. Histopathological studies confirmed the diagnosis of an occult AVM. Classically, these lesions are not visualized with angiography.Our patient's cerebral angiography and MR investigations were all normal. To our knowledge this is the first case in literature in which intracranial haemorrhage (acute subdural haematoma, intracerebral haematoma, SAH) occurred due to hyperperfusion of angiographically occult vascular malformation. PMID- 20591260 TI - Letter to the editor. PMID- 20591261 TI - Errata corrige: int. Neur. 9: 99-126:"protected" wallstenting of atheromatous stenoses at the carotid bifurcation. PMID- 20591262 TI - "Protected" wallstenting of atheromatous stenoses at the carotid bifurcation. AB - SUMMARY: Atheromatous stenoses at the carotid bifurcation were treated by angioplasty and Wallstenting with cerebral protection obtained in most cases by temporary occlusion of the internal carotid artery. 287 carotid stenoses were treated in 233 patients. The stenosis was symptomatic in 79% of cases. All patients presented either a stenosis of >70% with significant impairment of the cerebral circulation (281 cases) or a symptomatic ulcerated plaque (six cases). A self-mounted protection system was used in 177 cases, the Percusurge Guardwire protection device in 98 cases an EPI filter in 12 cases. There was a contralateral internal carotid occlusion in 13% of cases. A combined stenting (vertebral, siphon, subclavian) was performed in 14% of cases. A Rolling membrane Wallstent was used in 84 patients, a first generation Easy Wallstent in 38 cases, a "Carotid" Easy Wallstent 35 in 55 cases and monorail 14 in 110 cases. Full opening of the stenosis was obtained in 98% of patients with correction of the arterial curve and improvement of the cerebral vascular supply. There were 0.7% cases with transient symptomatic neurological complications and 2% with permanent sequelae mainly related to avoidable inadequacy in flushing or to the insufficient radial force of the first generation Easy Wallstent. There were no per and one post-procedural cardiac complication (0.6%) in the s165 cases performed with the "Carotid" Easy Wallstent. Follow-up angiograms showed 0.7% of restenoses. Still in evolution, endovascular treatment of atheromatous stenoses at the carotid bifurcation with cerebral protection and stenting is a promising alternative technique to surgery. The association of Carotid Easy Wallstent 14 monorail and Percusurge Guardwire appears to be currently satisfactory. PMID- 20591263 TI - The Underlying Mechanisms of Endovascular Exclusion of Intracranial Aneurysms by Coils. How Important is Electrothrombosis? AB - SUMMARY: Endovascular coil treatment of intracranial aneurysms is now widely accepted. We discuss some of the arguments for the relative roles of electrothrombosis, spontaneous thrombosis, mechanical filling, haemodynamic effects and surface properties in successful coil treatment. Despite an enormous body of literature, with many theories and much data, there is limited evidence for, or understanding of, the mechanisms by which coil treatment protects against aneurysm rupture. It seems likely that electrothrombosis plays no part.Dense packing is probably important in preventing recurrence. New technologies aiming to encourage endothelialisation and increased connective tissue formation appear promising. PMID- 20591264 TI - 3D Micrus Coil "Cage" in Wide-Necked Aneurysms. AB - SUMMARY: We aimed to verify that Micrus 3D microcoils can be used as first coils in the treatment of saccular wide-necked aneurysms to provide stable protection to the neck by keeping the coil mesh inside the aneurysm. We selected 22 wide necked aneurysms and calculated the ratio between sac diameter and neck width which was close to unity. The aneurysms were treated by endovascular approach using Micrus 3D (Spherical) microcoils as first coils. The coils proved stable during placement and detachment and compatible with both GDC and Micrus coils used for filling and packing. The endovascular procedure was suspended in only two out of 22 aneurysms selected for treatment. Aneurysm bleeding occurred in two endovascular procedures but was controlled. No complications were encountered in the remaining 18 patients treated. The percentage of technical failures has been reduced since the adoption of 3D Micrus microcoils in our practice. PMID- 20591265 TI - Treatment and Short-Term Follow-up of Symptomatic Atherosclerotic Intracranial Artery Stenosis by Stent-Assisted Angioplasty. AB - SUMMARY: Atherosclerotic intracranial artery stenosis can cause hypoperfusion of brain tissues and embolus formation, causing stroke. Conservative medical treatment seemed to have little effect on the natural history and prevent the stroke attack caused by artery stenosis. The purpose of stent-assisted angioplasty is to reconstruct the damaged vessels: the indications, feasibility, effectiveness, complications and follow-up for this new treatment method are discussed. A series of 32 cases with symptomatic intracranial artery stenosis were accepted from 1998 to 2002. The mean age was 42 yrs (31 ~ 76 yr), male/female ratio=23/9. All patients were refractory to optimal medical therapy. Lesions included 12 middle cerebral arteries (37.5%), six basilar arteries (18.75%), three distal ICAs (9.38%) and 12 intracranial Vas (37.5%). All patients were treated by methods of transluminal stent-assisted angioplasty under general anesthesia. Patients were premedicated with Aspirin (300mg/per day) and Ticlopidine (250mg/per day), this was continued for six weeks after the procedure. Medical history, anamnesis, and treatment protocol were reviewed and evaluated retrospectively, shortterm follow-up (2mths ~ 1 yr) was also obtained. Primary clinical presentations were TIAs (21/32, 65.63%), minor stroke ( 8/32, 25%) and severe stroke (3/32, 9.38%). 31 cases (96.86%) were successfully implanted with coronary stents within the stenosed vessels; technical success rate was 96.86%. Instant angiographic results showed the stenosed extent had decreased from 72.36% +/- 5.69 to 10.16% +/- 6.94. One vessel ruptured during the procedure, the patient recovered after surgical repair of the ruptured vessel. Clinical follow-up demonstrated symptoms resolved in most patients (30/32, 93.75%) within the follow- up period, two cases with MCA stenosis had TIAs within two months after the procedure. 12 cases accepted angiographic follow up.Velocities of stented vessels of five cases (5/21, 23.81%) increased compared to instant results, suggesting restenosis, three of them were confirmed by angiography which included two cases with MCA stenosis (figure 3) and one with distal VA, one of the five cases had recurred TIAs. With the newer generation of coronary stent, this technique seemed safe, feasible and effective to prevent stroke attack, but the indication is very important for the technical success. Restenosis remains a common problem as with coronary stenting. Long-term follow up will be needed. PMID- 20591266 TI - Prenatal diagnosis of unusual fetal pial arteriovenous malformation. A case report. AB - SUMMARY: Cerebral arteriovenous malformations (CAVMs) are rarely diagnosed in utero. Most prenatal imaging of intracranial vascular malformations relates to Vein of Galen aneurysmal malformations (VGAMs) or Dural Arteriovenous Malformations (D-AVMs). We report a case of a fetal pial AVF with multiple fistulae and venous pouches, which appeared as an anechoic lesion on the prenatal ultrasound scan. The patient was asymptomatic with normal postnatal growth. No haemodynmaic disturbance was evident. Postnatal Computed tomography (CT), Magnetic Resonance Imaging (MRI) and catheter Digital Subtraction Angiography (DSA) confirmed the presence of a pial AVF. The angiographic findings and family history of nose bleeds suggests the diagnosis of Hereditary Hemorrhagic Telangiectasia. The largest AVF was embolized with tissue adhesive; the residual AVF subsequently removed by surgical excision. PMID- 20591267 TI - Multifocal cerebral venous malformations and associated developmental venous anomalies in a case of blue rubber bleb nevus syndrome. AB - SUMMARY: We report a sporadic case of probable BRBN (blue rubber bleb nevus syndrome) with multiple CNS (central nervous system) involvement. These features consisted of multiple VMs (venous malformations) and DVAs (developmental venous anomalies) in supratentorial brain, cerebellum, and diencephalon. Since its first description by Bean, there have been many cases of BRBN manifesting with gastrointestinal bleeding with or without associated hemorrhage. Cases with CNS involvement were rarely reported and many of the descriptions were confusing with different terminologies used to describe them such as capillary venous malformation, hemangiomas, and vascular malformations. The lesions illustrated are venous malformations similar to our case. The association of DVA was recognized in some cases; they are likely to be underestimated when revisiting the published case illustrations.Although our case is sporadic, the link with HHT1 is unlikely despite the involvement of the same chromosome (Ch 9). PMID- 20591268 TI - Non-aneurysmal perimesencephalic subarachnoid haemorrhage with associated pontine haemorrhagic infarction. A case report and subject review. AB - SUMMARY: Non-aneurysmal perimesencephalic subarachnoid saemorrhage is characterized by an accumulation of blood in the perimesencephalic and prepontine cisterns identified on sectional imaging together with persistently negative cerebral angiography. Magnetic resonance imaging usually contributes no further information on the possible cause of the bleed but may occasionally show further features including associated parenchymal infarcts such as the pontine haemorrhagic infarct seen in the case described here. PMID- 20591269 TI - Bilobed wide neck posterior cerebral artery aneurysm associated with fusiform basilar aneurysm, subarachnoid hemorrhage and chronic renal failure. A case report. AB - SUMMARY: A 56 year-old woman presented with a ruptured bilobed wide neck aneurysm of the P2 segment of the PCA, atherosclerotic fusiform basilar artery aneurysm, subarachnoid bleeding with negative CT scan and chronic renal failure. She was managed by a cooperative approach involving neurosurgeons, neuroradiologist, neurointensivist, emergency room physicians, nurses and technicians. She underwent operation by proximal clipping for the aneurysm of the PCA. Postoperative neurological deficits include homonymous hemianopsia and ipsilateral third nerve palsy. The operation was performed through asubtemporal approach. At surgery, the aneurysm was located in the distal of the P2 segment of PCA, bilobed up and down, no definitive neck with small distal branches, and was treated by proximal clipping of the PCA aneurysm. The fusiform basilar artery aneurysm was severely atherosclerotic and left untouched. This is a rare case which required a high index of suspicion to detect subarachnoid bleeding from ruptured posterior fossa aneurysm, accurate prediction of the site of bleeding and the location of aneurysm location by conventional angiogram, MRI and MRA, and careful planned surgical strategy with the right approach for the P2 segment of the PCA aneurysm, complicated post operative care with airway management, triple H therapy, nutrition, additional measures and multiple hemodialysis. PMID- 20591270 TI - Two Distally Located Right SCA Aneurysms: Endovascular Treatment by Parent Artery Occlusion with GDC Coils and N-BCA Injection. Case Report and Review of the Literature. AB - SUMMARY: Peripheral aneurysms of the superior cerebellar artery are considered difficult to treat surgically and endovascularly because of their inaccessibility. Parent artery occlusion is therefore frequently the preferred method. Embolic materials previously reported in this situation are either GDC coils or a polymerizing agent (n- BCA). We report a patient with two distally located, wide-neck aneurysms of the right superior cerebellar artery who presented with hemorrhage and was treated by endovascular embolization of the parent artery using a combination of GDC coils and n-BCA. PMID- 20591271 TI - Endovascular treatment of traumatic intracranial aneurysm in an infant. A case report. AB - SUMMARY: Traumatic intracranial aneurysms in children are rare and mostly related to skull fracture or rapid decelerating closed head injury.We report the case of an infant who developed intracranial aneurysm after minor head trauma and managed by endovascular treatment. A seven-month-old infant presented with delayed intracranial hemorrhage following minor head trauma. Cerebral angiography disclosed a multilobulated fusiform aneurysm involving the right anterior cerebral artery (ACA) distal to the anterior communicating artery. Endovascular treatment of the aneurysm was performed and the infant made an excellent recovery during six months clinical and radiological follow-up. Delayed presentation of intracranial hemorrhage with acute deterioration in the infant after head trauma warrants angiography for proper diagnosis and management of the traumatic aneurysm, which has a high mortality rate after rupture and rebleeding. Endovascular treatment of traumatic aneurysm is feasible in infants, and occlusion of distal intracranial arterial aneurysms can be safely and precisely achieved using current coil technology. PMID- 20591272 TI - Rebleeding and ischemia after acute endovascular treatment of ruptured dissecting subarachnoid vertebral artery aneurysms. AB - SUMMARY: Dissection aneurysms of the vertebral artery represent 3.2% of all cerebral aneurysms and 28% of intracranial dissection aneurysms. Dissection of the vertebral artery in its intracranial segment (V4) usually causes a subarachnoid hemorrhage (SAH) from subadventiatial extension of the vessel wall hematoma. Rarely (one case in seven), the symptomatology is characterized by brain stem ischemia from the vertebral artery and/or postero-inferior cerebellar artery occlusive dissection. The high rebleeding (18-33% with a 10+/-5 day interval between the first and the second bleeding) and mortality (> 45%) rates 1, 13 of this disease prompt emergency treatment usually consisting in endovascular coiling of the dissection aneurysm and/or the dissected segment of the parent vessel. Herein we report our experience in endovascular coiling of acutely ruptured dissecting aneurysms of the vertebral artery dissection in V4 segment. We focus the discussion on the risk of rebleeding and the ischemic complications that my occur after endovascular or surgical treatment. PMID- 20591274 TI - Functional vascular anatomy of the head and neck. PMID- 20591273 TI - Simultaneous Cerebral Aneurysms and Carotid Disease Should the Symptomatic Lesion always be the first to be Treated? A Case Report. AB - SUMMARY: Simultaneous presentation of carotid stenosis and cerebral aneurysms is rare and it is conventionally accepted that symptomatic lesions need to be treated first. Our purpose was to describe our experience in managing patients who simultaneously presented significant carotid stenosis and cerebral aneurysm. PMID- 20591275 TI - Pediatric Pial AVF. PMID- 20591276 TI - Endovascular management of cerebral aneurysms. PMID- 20591277 TI - Welcome address. PMID- 20591278 TI - Birthmarks: diagnosis and therapy. PMID- 20591279 TI - Thrombolysis in acute ischemic stroke. Intra-arterial and intra-venous. AB - Objectives for Presentation: 1. Review thrombolytic trials in acute ischemic stroke. 2. Discuss current recommendations for acute ischemic stroke therapy. 3. Discuss the role of intra-arterial thrombolysis in acute ischemic stroke. 4. Discuss the newest thrombolytic trials and recommendations for therapy in acute stroke prevention and management. PMID- 20591280 TI - Intracranial dural arteriovenous shunts in children. The toronto experience. PMID- 20591281 TI - Management of acute vascular injuries. PMID- 20591282 TI - Endovascular treatment in direct carotid cavernous fistula. PMID- 20591283 TI - Vertebroplasty. PMID- 20591284 TI - Interventional Procedures Under CT Guidance in Pain Management. (Cementoplasty Excluded). PMID- 20591285 TI - Mini-invasive treatment of herniated disc by oxygen-ozone injection. PMID- 20591286 TI - Radioactive coil embolisation of intracranial aneurysms. Experimental and preliminary clinical data. PMID- 20591287 TI - Endovascular treatment of intracranial aneurysms. "An update". PMID- 20591288 TI - Dissecting aneurysms. Endovascular treatment. PMID- 20591289 TI - Microsurgical approach to giant intracranial aneurysms. PMID- 20591290 TI - Dural AVFS. Clinical Presentation, Classification and Angiograpic Evaluation. PMID- 20591291 TI - Cerebral dural arteriovenous fistula. PMID- 20591292 TI - Surgical treatment of spinal cord vascular malformations. PMID- 20591293 TI - Brain AVM. Relationship of Angioarchitecture and Clinical Symptoms and Implications for Treatment. PMID- 20591294 TI - Endovascular treatment of B-AVM. PMID- 20591295 TI - Gamma knife radiosurgery in cerebral arteriovenous malformations. PMID- 20591296 TI - Brain AVMs Endovascular Treatment. PMID- 20591297 TI - Permanent inflammatory effect of N-butylcyanoacrylate on vascular wall immunohistochemical analysis. AB - SUMMARY: We report a case with atypical pattern and time course of inflammatory response after partial embolization of a cerebral arteriovenous malformation with N-butylcyanoacrylate (NBCA), examined by immunohistochemical analysis. This pathomorphological finding of permanent acute inflammation has not been previously reported in humans. PMID- 20591298 TI - Effects of endothelial injury on the rate of thrombus organization in canine carotid arteries occluded with microcoils. AB - SUMMARY: Thrombus organization in canine carotid arteries occluded with platinum microcoils was studied to determine if endothelial injury created with a Xenon Chloride Excimer Laser (XEL) could acclerate endovascular fibrosis. Ten common carotid artery stumps were created in ten dogs. Each of four stumps were schematically divided into four longitudinally contiguous injury zones (thermal ablation injury, non-ablative injury, proximal and distal non-injury zones) to test the effects of ablative and non-ablative injury and to establish a set of internal controls that would account for proximity to circulating blood at the ostium of the occluded artery. Following XEL irradiation of the endothelium through an arteriotomy, each stump was embolized with microcoils. Four control stumps were subjected to sham laser procedures, and embolized in an identical fashion. Two additional stumps were embolized in the absence of sham surgery. Angiographic, gross and histologic analysis was performed after four weeks. Specimens of freshly clotted whole blood mixed with microcoils were used as an additional control. In irradiated stumps and non-irradiated stumps (sham and embolization only), angiography revealed no evidence of coil compaction or recanalization. In all irradiated stumps the thermal ablation zone contained fibrous tissue and neovascularity without unorganized thrombus. The other zones in the irradiated stumps were indistingnishable from each other and from all zones in the non-irradiated sham stumps, containing primarily unorganized thrombus. Stumps embolized in the absence of sham surgery were filled with material that was grossly and microscopically identical to specimens of freshly clotted whole blood containing microcoils. The results indicate that thermal ablation injury of the endothelium accelerates thrombus organization in canine carotid arteries occluded with platinum microcoils. PMID- 20591299 TI - Factors Leading to and Treatment of Aneurysmal Perforation during Coil Embolization. Analysis of 105 Consecutive Cases. AB - SUMMARY: It is important to know the characteristics of aneurysms that tend to cause perforation and treatment of these perforations to reduce the morbi/mortality of the endovascular treatment for intracranial aneurysms. Factors leading to aneurysmal perforation were analyzed from the view points of aneurysmal status (ruptured or unruptured), size and direction of aneurysmal dome from the parent artery and treatment of perforation during GDC embolization was discussed in 105 consecutive cases. Perforation occurred in three small aneurysms (less than 3 mm in diameter or depth) where the direction of the dome is the same as that of microcatheter advancement. Perforation occurred when a microcatheter was advanced to counteract catheter recoil caused by coil deployment. Haemorrhage occurred in all cases immediately following microcatheter and coil perforation into the subarachnoid space. In all cases, bleeding was controlled by deploying the coil so that it extended from the subarachnoid space back into the intraaneurysmal cavity. In two cases, surgical clipping was required to treat the incompletely obliterated aneurysm. No additional permanent neurological deficit occurred as a result of any of the three perforations. Special care should be taken during the embolization of small aneurysms (less than 3 mm in minimal diameter) where, owing to the shape of the lesion, or fixation of a microcatheter by the stent strut, the antegrade force of the canulating microcatheter is transmitted directly toward the aneurysm dome. PMID- 20591300 TI - Natural history and treatment modalities of symptomatic bilateral middle cerebral artery stenosis. AB - SUMMARY: To assess the natural history, pathogenesis, and treatment modalities of symptomatic bilateral middle cerebral artery stenosis, we retrospectively evaluated a consecutive series of patients for their medical history, anamnesis, and our treatment protocol. Treatment included transluminal angioplasty, bypass surgery and/or conservative antiplatelet therapy for prevention of the stroke attack and vessel reconstruction. Indications, feasibility, effectiveness, and complications of treatment are also discussed. A series of 19 patients with symptomatic bilateral middle cerebral artery (MCA) stenosis were treated consecutively from 1998 to 2002. Medical history, anamnesis, and treatment protocol were reviewed and evaluated retrospectively, Of these 19 patients, six (six vessels, 31.57%) were treated by balloon (two vessels) or stent-assistant angioplasty (four vessels), four (four vessels, 21.05%) were treated by bypass surgery, 18 vessels plus ten vessels occluded before treatment (47.37%) were conservatively treated by antiplatelet agents. 24 vessels (12 patients) were followed from three months to four years by angiography (nine cases), TCD (12 cases), or MRA (five cases). A total of 38 vessels were involved (19 vessels), of which ten vessels (10/38, 26.31%) had occluded before coming to our hospital. Three patients (3/19, 15.78%) had a history of hypertension, five had a history of smoking. The mean age of these 19 patients was 33 yrs (24 ~ 42 yrs), with a slight male preponderance (males/females = 13/6). Initial clinical presentations were TIAs (14/19, 73.68%) and minor stroke (5/19, 26.32%), symptoms attacked alternatively for five patients (5/38, 13.16%). Seven vessels (7/28, 25%) occluded within one to three years, of which three occluded asymptomatically, four acutely occluded vessels accompanied acute stroke. Nine vessels (9/28, 32.14%) were treated by conservative antiplatelet agents and one treated by bypass surgery had related recurrent TIAs. Vessels treated by angioplasty (balloon or stent) remained patent and free of symptoms. The stenosed bilateral MCA may occlude within one to three years without intervention. The pathogenesis of this special disease is unclear, it may be genetic or due to asymptomatic infection. The results showed that earlier appropriate treatment can resolve the clinical symptoms and somehow change the natural history of this disease. Conservative medical therapy cannot prevent further stroke attack. Collaterals are very important for these special patients. PMID- 20591301 TI - Moyamoya Disease is a Progressive Occlusive Arteriopathy of the Primitive Internal Carotid Artery. AB - SUMMARY: The purpose of this literature review is to disclose the relationship between the temporal profile of steno-occlusive changes in the cerebral arteries in moyamoya disease and the embryological evolution of the cerebral arteries. Steno-occlusive changes and progression occur in the sequence of embryological evolution of the primitive internal carotid artery in the early embryological stage. In other words, steno-occlusive changes in the cerebral arteries occur primarily near the bifurcation of the cranial and caudal divisions of the primitive internal carotid artery, evolve from the cranial division to the caudal one, and progress from the bifurcation centrifugally. Steno-occlusive changes do not occur essentially in the distal cortical branches of the primitive internal carotid artery, in any arteries in the external carotid system, which are derived from ventral pharyngeal system and primitive stapedial system, or in any cerebral arteries in the vertebrobasilar system, which are derived from the longitudinal neural arteries.These facts suggest that moyamoya disease is strongly related to the vasculogenesis of the primitive internal carotid artery and genetic factors play a major role in the clinical manifestations of moyamoya disease. PMID- 20591303 TI - Statement of a proud agnostic. PMID- 20591302 TI - MTI (Dendron) Variable Detachable Coils. Preliminary Clinical Experience in Cerebral Aneurysms in Glasgow. AB - SUMMARY: We present our initial clinical experience of Dendron Variable Detachable System (VDS) coils, now Sapphire VDS from MTI, in the endovascular treatment of cerebral aneurysms. VDS coils, uniquely, can be detached at variable points along their length, allowing placement of as much or as little as desired of the coil within the aneurysm. Our ten patients formed part of a multicentre feasibility study. VDS coils were successfully deployed in all but one aneurysm. The electrolytic detachment mechanism with practice is both simple to use and reliable. The coils are however slightly stiffer than standard coils limiting their use in small aneurysms. This remains a technology in evolution. PMID- 20591304 TI - MR Perfusion Imaging in a Case of a Vein of Galen Malformation with Secondary Capillary Angioectasia. AB - SUMMARY: Vein of Galen Aneurysmal Malformations (VAGMs) are uncommon vascular malformations associated with dilatation of the vein of Galen embryonic forerunner with single or multiple direct arteriovenous fistulas within its wall without direct reflux into normal cerebral veins. We describe a patient with a late neurological onset presenting a classic VGAM complicated by secondary thalamic capillary angioectasia imaged with MR perfusion. In our patient, abnormal MR perfusion parameters were not seen on conventional MRI; they probably reflect underlying venous hypertension. They were located in areas involved in motor neurological deficit. PMID- 20591305 TI - Endovascular Treatment of a Dural Arteriovenous Fistula of the Transverse Sinus by Recanalisation, Angioplasty and Stent Deployment. A Case Report and Follow-up. AB - SUMMARY: We report the endovascular treatment of a 40- year-old woman with bilaterally thrombosed transverse sinuses and a dural arteriovenous fistula (DAVF) causing cortical venous reflux by recanalization, angioplasty and stent deployment of the occluded sinus segment followed by occlusion of the DAVF by stent deployment in the fistulous segment. By recanalization of the occluded sinus we re-established normal anterograde venous drainage and eliminated the venous hypertension and cortical venous reflux. After the procedure, the patient was treated with aspirin and clopidogrel for three months. A follow- up examination showed total occlusion of the DAVF, patency of the sinus and a complete resolution of the clinical symptoms. PMID- 20591306 TI - Coexistence of Mandibular Arteriovenous Malformation and Cerebellar Arteriovenous Malformation. An Example of Cerebrofacial Arteriovenous Metameric Syndrome Type III. AB - SUMMARY: We describe a patient with cerebellar and mandibular arteriovenous malformations who initially presented with oral haemorrhage and then subsequently had a cerebellar haemorrhage. This is the second reported case of cerebrofacial arteriovenous metameric syndrome type III (CAMS III) in the literature and we discuss the role of homeobox genes in craniofacial development and angiogenesis. PMID- 20591307 TI - Spinal arteriovenous malformation associated with a radicular arteriovenous fistula suggested a metameric disease. A case report. AB - SUMMARY: A spinal intramedullary arteriovenous malformation (AVM) associated with a radicular arteriovenous fistula (AVF) is reported. The patient had mild myelopathy and low back pain. Spinal angiography revealed the AVM fed by the anterior spinal artery via left T10, T11 and right L1 radiculomedullary arteries and the radiculopial arteries of left L1, L2 and right T11, L3 levels and the radicular AVF at the left L4 level. There were three radiculomedullary arteries within four levels in our case. This spinal AVM associated with a radicular AVF is considered a genetic nonhereditary lesion with metameric link. PMID- 20591308 TI - Venous sinus stent-assisted angioplasty for refractory benign intracranial hypertension. AB - SUMMARY: Two patients with dural sinus stenosis of different causes presenting with refractory benign intracranial hypertension were confirmed by angiogram. Stent-assistant angioplasty was used to dilate the stenosed sinusesand led to prompt clinical improvement. Relative long-term followup showed good patency of the stented sinuses. PMID- 20591309 TI - Coil-Induced Perforation of Recently Ruptured Cerebral Aneurysm during Embolization. Causes and Avoidance. AB - SUMMARY: Most coil-induced aneurysmal ruptures during endovascular treatment occur in small, recently ruptured aneurysms, and after placement of at least one coil. In cases where the distal part of the microcatheter cannot move back due to its straightness and tightness, the last coil deployed may advance towards the aneurysmal wall through intercircles of deposited coils. To solve this problem, after complete occlusion of the sac is obtained, the microcatheter is slightly withdrawn until the tip of the catheter is placed in the neck, and then the neck is occluded with the appropriate coil. PMID- 20591310 TI - Letter to the editor. PMID- 20591311 TI - Neuro-intervention costs. PMID- 20591312 TI - "From operative morbidity to risk management". PMID- 20591313 TI - Presurgical embolization of spinal tumours using glubran 2 acrylic glue. AB - SUMMARY: This study aimed to define the indications, technique and results of presurgical embolization of spinal tumours using Glubran 2 acrylic glue. Embolization was performed prior to surgery in eight patients with benign tumours and 11 patients with malignant lesions. The main embolization agent used was Glubran 2, a new acrylic glue with the EC mark, suitable for permanent embolization of the pathological circulation of primary and secondary spinal tumours. All the procedures were technically feasible and achieved partial or complete embolization of the vascularized lesion without periprocedural complications. Glubran 2 proved easy to use with excellent intravascular penetration achieving permanent embolization. The degree of presurgical embolization in terms of surgical field haemostasis was correlated with the degree of vascular occlusion achieved. PMID- 20591314 TI - In-Vitro Simulation of NBCA Embolization for Arteriovenous Malformation. AB - SUMMARY: Embolization using n-butyl-cyanoacrylate (NBCA) for arteriovenous malformation (AVM) is now a daily practice over the world, but there exists no objective data that can be a basis for discussion or decision-making on the best concentration and injection rate of NBCA mixture. The purpose of this study was to obtain objective data on control and behavior of NBCA mixture with an in vitro simulation system of NBCA embolization for AVM. A nidus model made of a one-ml syringe filled with small beads was connected to a pulsatile flow circuit. A microcatheter was introduced just before the nidus model. Endoluminal pressures proximal and distal to the nidus and flow volume through the nidus were measured. Digital subtraction angiography (DSA) was performed to calculate transit time of the contrast medium (CM) through the nidus. NBCA was injected at various rates with an autoinjector and transit time of NBCA through the nidus was calculated. 27 trials were completed. Transit time of CM through the nidus model is well correlated to flow volume per unit of time through the nidus model. Shorter the transit time, larger was the flow volume per unit of time. The correlation was statistically significant (P < .0001). Though statistical significance was not attained, transit time of NBCA mixture at 50% concentration had a tendency to be correlated to flow volume per unit of time through the nidus, and slower injection of the NBCA mixture led to slower filling of the nidus model. Though this simulation system was artificial and the results should be interpreted carefully, it was shown with this system that transit time of CM through the nidus could be a good index for flow volume per unit of time through the nidus. Also suggested was a possibility to utilize this in vitro system for research and training on NBCA embolization of AVM. PMID- 20591315 TI - Endovascular treatment of giant p1/p2 aneurysm by direct puncture of the vertebral artery. Case report. AB - SUMMARY: Vascular access is usually achieved through a femoral arterial puncture using a modified Seldinger technique. However, selective catheterization of the great cerebral vessels by femoral approach fails completely when the vessel is tortuous or atheromatous. In case of posterior vascular circulation aneurysms, transbrachial approach or direct puncture of the vertebral artery (VA) is an alternative. The aneurysms of the posterior cerebral artery (PCA) are reported to be rare. Due to unfavorable anatomic location, the PCA aneurysms are difficult to reach during surgical procedure. Endovascular embolization is at present considered to be more effective and safer treatment of the PCA aneurysms arising from different segments, offering a viable alternative to the surgical approach. We report the case of the giant left PCA aneurysm, located at the junction of P1/P2 segments, successfully treated by parent artery occlusion achieved after the direct puncture of the right VA which was used because both VAs were tortuous, irregular and their ostia were not accessible by femoral approach. According to different authors, parent artery occlusion appears to be safe in the treatment of P2 segment aneurysms, whatever the location of the occlusion. In our case we decided to perform this kind of treatment believing it was the only possible one. PMID- 20591316 TI - Secondary spontaneous thrombosis of a giant aneurysm located distally on a feeding artery after embolization of an associated arteriovenous malformation. AB - SUMMARY: Giant aneurysm located in the distal part of the feeding artery associated with a cerebral arteriovenous malformation is rare and the treatment is clinically challenging. We report the spontaneous and complete thrombosis of a flow-related giant aneurysm immediate up-stream to a cerebral arteriovenous malformation by embolization of that malformation alone in a patient presenting with complex partial seizure and no history of intracranial haemorrhage. We obviated the need to directly intervene on the giant aneurysm, thus reducing unnecessary procedure related risks to the patient. Follow up one year later confirms the thrombosis and show shrinkage of the mass. The patient is asymptomatic. PMID- 20591317 TI - Type D Traumatic Carotido-cavernous Fistula due to Selective Transection of the Inferolateral Trunk(ILT). Diagnosis and Endovascular Treatment. AB - SUMMARY: A minority of traumatic carotido-cavernous fistulas (CCF) are of the indirect variety, and then usually supplied only by meningeal branches of the ipsilateral external carotid artery (Type C).We describe a case of a Type D CCF due to traumatic injury of the inferolateral trunk (ILT), and describe its angiographic features and endovascular management through both the external and internal carotid arteries following a failed transvenous approach. PMID- 20591318 TI - Paravertebral arteriovenous malformation supplied by branches of the iliac arteries. AB - SUMMARY: Arteriovenous malformations of the spine and spinal cord can be classified into spinal cord arteriovenous malformations (AVMs) and fistulas (AVFs) and dural AVM and AVF occurring outside the dura but draining into the epidural veins called paravertebral AVM and AVF 1. Paravertebral malformations are rare arteriovenous communications outside the dura but draining into the epidural veins. These malformations produce symptoms from either venous congestion of the cord or cord compression from dilated epidural veins resulting in a myelopathy.We present a case of a patient with a lumbar paravertebral malformation treated successfully by endovascular occlusion of the feeders. PMID- 20591319 TI - Double internal carotid origin of the ophthalmic artery with ruptured aneurysm of the posterior communicating artery. A case report. AB - SUMMARY: We report a case of double origin of the ophthalmic artery from the carotid siphon. The persistence of the primitive dorsal ophthalmic artery, together with a ventral ophthalmic artery, constitutes the double origin of the ophthalmic artery. Remnant of intraorbital anastomoses formed by these two arteries is demonstrated. This represents a rare configuration of double origin of the arterial blood supply, which is discovered "incidentally" in a patient harboring a ruptured aneurysm of the posterior communicating artery. The embryology of the ophthalmic artery and a possible association between vascular anomaly and arterial aneurysm can be envisaged. PMID- 20591320 TI - A novel microcatheter-delivered, highly-flexible and fully-retrievable stent, specifically designed for intracranial use. Technical note. AB - SUMMARY: A new microcatheter-delivered, highly-flexible, fully-retrievable intracranial stent has been developed in order to facilitate the endovascular treatment of wide-necked aneurysms, though it might also prove useful for other intracranial pathology. The nitinol stent has radiopaque proximal and distal markers, is available in a wide range of sizes and is as flexible as a micro guidewire. It is electrolytically detached, allowing retrieval even after full deployment. The stent is compatible with all currently available embolic agents and does not degrade MR images. PMID- 20591321 TI - Three-Year Retrospective Study of Complications Arising during Interventional Procedures. AB - SUMMARY: This retrospective study aimed to assess the percentage of complications arising in our daily practice of interventional procedures, comparing our findings with those of leading international reference centers and accepted guidelines for endovascular treatment. During the threeyear period considered (2000-2002), we performed 246 interventional procedures, divided into seven different pathological conditions: aneurysms, brain AVMs dural and carotid cavernous fistulae, spine-spinal cord tumours, headneck tumours, carotid stenosis and thrombolysis. Aneurysmal disease accounted for 45% of all endovascular procedures. In conclusion, four periprocedural complications arose in the course of 246 procedures resulting in one death and three cases of permanent neurological deficit (2%). PMID- 20591322 TI - Dural Sinus Malformations (DSM) with Giant Lakes, in Neonates and Infants. Review of 30 Consecutive Cases. AB - Abstract: Background and Purpose. Dural Arteriovenous Shunt (DAVS) in children include Dural sinus malformation (DSM), infantile and adult types. They are rare and seldom reported. Our purpose was to highlight the angiographic features of the DSM sub group for prognosis of clinical evolution and outcome and to lay guidelines for management. METHODS: From a dedicated neurovascular data bank, there were 52 cases of arteriovenous dural shunts in children from 1985 to 2003. Of these, there were 30 patients with DSM, which we analysed the various angioarchitecture, presentation and neurological outcome. Children clinical status was evaluated and scored at admission and follow up. Results. There was an overall male dominance of 2:1. Antenatal diagnosis was obtained in 8/30 (26.7%) cases. Mean age of diagnosis was 5 months. Mean age at first consultation was 8.7 months. No patient was diagnosed during childhood. The most common clinical presentations were macrocrania 76.7%, seizures 23.3% and mental retardation 23.3%. In 14/30 (35.7%) of the patients, the therapeutic decision was to manage conservatively; in 5/14 (30.7%) with predictable favourable evolution and in 9/14 (64.3%) with irreversible poor neurological outcome. In the remaining 16/30 (53.3%) patients, endovascular treatment was performed. In 12/16 (75.0%) patients the neurological outcome was good, 3/16 (18.8%) patients had unfavourable evolution despite embolization. There was no morbidity mortality related to the procedures themselves. 1/16 (6.3%) patient was lost to follow-up. Overall 12/29 (45.8%) patients had an unfavourable neurological outcome with 11 patients dead and 1 with severe neurological deficit. In the surviving group of children, 17/18 (94.4%) have a good neurological outcome; in 10/18 (55.5%) the lesion is morphologically excluded. Conclusion. DSM is rare disease with high mortality. They usually proceed to either total or partial spontaneous thrombosis before the age of 2 thus compromising normal cerebral venous drainage. DSM away from the torcular, good cavernous sinus, cavernous capture of sylvian veins, absence of pial veins, straight sinus or superior sagital sinus (SSS) reflux and absence of jugular bulb dysmaturation represent factors of good prognosis. Such patients will highly benefit for endovascular treatment. In partial endovascular approach the aim being is to separate the brain drainage from DSM drainage. This will be achieved by the transarterial approach to the associated mural arterio-venous shunts (AVS) and by disconnecting the pial reflux by transvenous route. PMID- 20591323 TI - Seminal plasma proteins inhibit in vitro- and cooling-induced capacitation in boar spermatozoa. AB - Dilute boar seminal plasma (SP) has been shown to inhibit in vitro capacitation and cooling-induced capacitation-like changes in boar spermatozoa, as assessed by the ability of the spermatozoa to undergo an ionophore-induced acrosome reaction. We hypothesised that the protein component of SP is responsible for this effect. To test this hypothesis, varying concentrations of total SP protein or SP proteins fractionated by heparin binding were assayed for their ability to inhibit in vitro capacitation, as well as cooling- and cryopreservation-induced capacitation-like changes. In vitro capacitation and cooling-induced capacitation like changes were prevented by 10% whole SP, as well as by total proteins extracted from SP at concentrations greater than 500 microg mL(-1). No amount of SP protein was able to prevent cryopreservation-induced capacitation-like changes. Total SP proteins were fractionated based on their heparin-binding properties and the heparin-binding fraction was shown to possess capacitation inhibitory activity at concentrations as low as 250 microg mL(-1). The proteins in the heparin-binding fraction were subjected to mass spectrometry and identified. The predominant proteins were three members of the spermadhesin families, namely AQN-3, AQN-1 and AWN, and SP protein pB1. We conclude that one or more of these heparin-binding SP proteins is able to inhibit in vitro capacitation and cooling-induced capacitation-like changes, but not cryopreservation-induced capacitation-like changes, in boar spermatozoa. PMID- 20591324 TI - Endocrine milieu of perioestrus in the giant panda (Ailuropoda melanoleuca), as determined by non-invasive hormone measures. AB - The aim of the present study was to determine the efficacy of faecal hormonal measures for evaluating ovarian activity in a significant sized cohort of giant pandas during the perioestrual period. Faecal excretion of oestrogen and progestagen metabolites corresponded with urinary patterns and receptive behaviours. Longitudinal assessment of 10 females revealed that, on average, faecal oestrogen concentrations started to rise (P < 0.05) above baseline (baseline mean +/- s.e.m.; 64.7 +/- 6.6 ng g(-1)) 5 days before the preovulatory oestrogen peak (484.6 +/- 126.8 ng g(-1)), which was followed by a gradual descent over 4 days to nadir. Mean faecal progestagen metabolite concentrations increased approximately twofold above baseline (from 186.2 +/- 37.7 to 347.2 +/- 75.7 ng g(-1); P < 0.05) during the 20-day interval after the preovulatory oestrogen surge. Variability within and among females precluded the use of a threshold of oestrogen or progestagen metabolites to predict reproductive status, yet faeces collected 2-3 days per week provided sufficient data to recognise that an individual was in the perioestrual period. Finally, in females that were examined for at least 3 consecutive years, there was an 18-53 day variation in the onset and an 8-13 day variation in the duration of perioestrual behaviour from year to year. In summary, these findings indicate that gonadal hormone profiles associated with the period immediately before, during and after oestrus are accurately revealed by analysis of the fibrous faeces of the giant panda. This approach has potential value for providing point-in-time information on the reproductive status of free-living individuals. PMID- 20591325 TI - Levonorgestrel, not etonogestrel, provides contraception in free-ranging koalas. AB - Management of high-density koala (Phascolarctos cinereus) populations is essential because of the browsing damage they inflict on their habitat. We have tested two types of gestagen implant, namely levonorgestrel and etonogestrel, as contraceptives for koalas. Free-ranging female koalas were given either a control, levonorgestrel (70 mg) or etonogestrel (34 or 68 mg) implant before the breeding season. Koalas were monitored every 4-12 weeks for births. Plasma progesterone was measured and a cytological smear of the urogenital sinus was taken. Fertility was high in the control group and the two etonogestrel-treated groups, with approximately 90% of females giving birth. In contrast, no levonorgestrel-treated female produced young during the study. Removal of levonorgestrel implants from six females reversed the contraceptive effect in the next breeding season, whereas the eight females in which the levonorgestrel implants were left in remained infertile for six breeding seasons. Vaginal cytology showed evidence of oestrous cycles during the breeding season in all females from all groups and there was no difference seen in the prevalence of cornified epithelial cells in the oestrous smears. This indirectly suggests that levonorgestrel does not prevent follicular development and oestrous cycling. Plasma progesterone in levonorgestrel-treated females remained low all year, but rose in controls concurrent with the onset of the breeding season. This suggests that levonorgestrel prevents pregnancy by blocking ovulation. Etonogestrel had absolutely no contraceptive effect at the two doses delivered and so is not suitable for controlling koala populations. In contrast, levonorgestrel was effective as a long-term, reversible contraceptive in wild koalas. PMID- 20591326 TI - Effects of oocyte vitrification on histone modifications. AB - Vitrification has been widely used as an assisted reproductive technology in animals and humans, yet the impact of oocyte vitrification and warming on survival and histone modifications has to be evaluated. In the present study, the survival of mouse MII oocytes was assessed after freezing, as were changes in histone 3 lysine 9 (H3K9) dimethylation, histone 4 lysine 5 (H4K5) acetylation and histone 3 lysine 14 (H3K14) acetylation. The results show that, in oocytes subjected to vitrification, H3K9 methylation and H4K5 acetylation were increased. H3K14 acetylation could not be detected in either non-vitrified or vitrified oocytes. Oocytes are very sensitive to changes in H3K9 and H4K5 following vitrification. Both these histone modifications could be useful markers to monitor epigenetic perturbations induced by various experimental vitrification protocols and eventually for optimising the cryopreservation of human oocytes. PMID- 20591327 TI - Effects of hexarelin (a ghrelin analogue) on fertilisation and the pre- and postnatal development of mice. AB - Ghrelin (Ghr) has been associated with reproductive physiology and pre- and postnatal development. The objectives of the present study were to evaluate the effects of hexarelin (HEX; 100 or 200 microg kg(-1) day(-1)), a therapeutic Ghr analogue, on: (1) embryo development 60 h post ovulation, induced pharmacologically, in pregnant mice; (2) the physical, neurobiological and sexual development of offspring of female mice injected with HEX during the first, second or third week of pregnancy or throughout the entire pregnancy; and (3) adult memory acquisition in these offspring. We also evaluated the effects of chronic HEX administration on memory acquisition in adult mice. Treatment of non pregnant female mice with HEX decreased ovulation rate. However, treatment of pregnant mice with HEX at any time during pregnancy tended to accelerate offspring maturation, regardless of bodyweight. This effect was only significant on neurobiological parameters following treatment during the first week. HEX treatment during the first week and/or throughout the entire pregnancy resulted in impaired memory acquisition in the offspring, with female mice being more susceptible to these effects. Similar results were observed for the effects of chronic HEX treatment on memory acquisition in adult mice. In conclusion, HEX seems to exert differential effects depending on when it is administered. Because HEX has started to be used therapeutically, its deleterious effects on ovulation and memory acquisition must be further evaluated. PMID- 20591328 TI - Disrupted imprinting status at the H19 differentially methylated region is associated with the resorbed embryo phenotype in rats. AB - Igf2, an imprinted gene that is paternally expressed in embryos, encodes an embryonic growth factor. An important regulator of Igf2 expression is methylation of the H19 differentially methylated region (DMR). A significant association has been observed between sperm methylation status at the H19 DMR and post implantation loss. In addition, tamoxifen treatment has been shown to increase post-implantation loss and reduce DNA methylation at the H19 DMR in rat spermatozoa. Because this DMR is a primary DMR transmitting epigenetic imprint information from the gametes to the embryo, the aim of the present study was to determine the imprinting status of H19 DMR in post-implantation normal and resorbed embryos (F(1)) and to compare it with the H19 DMR in the spermatozoa of the respective sires. Analysis of the H19 DMR revealed methylation errors in resorbed embryo that were also observed in their sires' spermatozoa in the control and tamoxifen-treated groups. Expression analysis of the reciprocally imprinted genes Igf2 and H19 showed significant downregulation of Igf2 protein without any effect on H19 transcript levels in the resorbed embryos. The results indicate an association between disrupted imprinting status at the H19 DMR in resorbed embryos and the spermatozoa from their respective sires regardless of treatment, implying a common mechanism of resorption. The results demonstrate transmission of methylation errors at the Igf2-H19 locus through the paternal germline to the subsequent generation, emphasising the role of paternal factors during embryogenesis. PMID- 20591329 TI - Decorin expression is decreased in human idiopathic fetal growth restriction. AB - Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in which the fetus fails to achieve its full growth potential in utero. Most cases of FGR are idiopathic and are associated with placental thrombosis. Previous studies suggest that proteoglycans, such as decorin, that contain the glycosaminoglycan dermatan sulfate are the principal anticoagulants in the normal placenta. The present study investigated decorin expression in placentas from pregnancies complicated by idiopathic FGR (n = 26) and gestation-matched controls (n = 27). Real-time polymerase chain reaction demonstrated significantly reduced decorin mRNA expression in FGR compared with control (1.52 +/- 0.14 v. 2.21 +/- 0.22, respectively; P < 0.01). Immunoblotting revealed decreased decorin protein (40 kDa) expression in FGR compared with controls (420.8 +/- 39.0 v. 690.1 +/- 42.2, respectively; n = 12 in each group; P = 0.0007). Immunohistochemistry demonstrated the presence of immunoreactive decorin protein in the placental villous stroma surrounding the fetal capillaries and a significant decrease in decorin protein presence in FGR compared with control (1.75 +/- 0.66 v. 2.98 +/- 1.12, respectively; n = 6 in each group; P < 0.01, t-test). This is the first study to demonstrate reduced decorin in idiopathic FGR, indicating a potentially significant role for decorin in the aetiology of placental thrombosis in idiopathic FGR. PMID- 20591330 TI - A-type lamin dynamics in bovine somatic cell nuclear transfer embryos. AB - The persistence of A-type nuclear lamin in somatic cell nuclear transfer (SCNT) embryos has been proposed as a marker for incomplete nuclear reprogramming. Using monoclonal antibodies to A/C- (A/C-346 and A/C-131C3) and B-type lamin, we compared distribution during early development of bovine IVF, parthenogenetic and SCNT embryos. A/C-346 staining was observed in the pronuclei of IVF embryos and in nuclei at the two-cell stage, but was not detected in subsequent cleavage stages up to and including hatched blastocysts. In contrast, A/C-131C3 and anti lamin B2 stained all preimplantation stage embryos. Parthenogenetic and SCNT embryos had similar staining patterns to IVF embryos for all three antibodies, demonstrating correct nuclear architecture reprogramming. Inhibiting protein synthesis with cycloheximide (CHX) in parthenogenetic and SCNT embryos did not affect lamin A/C localisation, suggesting that lamin A/C is maternal in origin. However, activation with CHX delayed lamin A/C incorporation compared with 6 dimethylaminopurine activation. In SCNT embryos, staining for both A/C- and B type lamin was delayed compared with parthenotes, although lamin B2 incorporation preceded lamin A/C in both. In conclusion, the lamin A/C distribution in SCNT bovine embryos paralleled that of IVF and parthenogenetic controls and therefore is not a marker of incomplete reprogramming. PMID- 20591332 TI - Prolonged interval between fusion and activation impairs embryonic development by inducing chromosome scattering and nuclear aneuploidy in pig somatic cell nuclear transfer. AB - The aim of the present study was to examine the effect of various intervals between electrofusion and activation (FA interval) on the nuclear remodelling and development of somatic cell nuclear transfer (SCNT) embryos in pigs. Reconstructed oocytes were activated at 0 (simultaneous fusion and activation; SFA), 1, 2 and 3 h (delayed activation) after electrofusion; these groups were designated as DA1, DA2 and DA3, respectively. When oocyte nuclear status was examined at 0.5, 1, 2 and 3 h after electrofusion, the incidence of chromosome scattering was increased (P < 0.01) as the FA interval was extended (0.0%, 12.0%, 77.3% and 78.0%, respectively). Extending the FA interval led to an increase (P < 0.01) in the percentage of oocytes containing multiple (>or=3) pseudopronuclei (PPN) (0.0% of SFA; 5.3% of DA1; 21.7% of DA2; and 33.5% of DA3). The development of SCNT embryos to the blastocyst stage was decreased (P < 0.05) in DA2 (5.7%) and DA3 (5.0%) compared with SFA (18.1%) and DA1 (19.5%). Our results demonstrate that extending the FA interval impairs the development of SCNT pig embryos by inducing chromosome scattering and the formation of multiple PPN, which may result in increased nuclear aneuploidy. PMID- 20591331 TI - Role of Fyn kinase in oocyte developmental potential. AB - Fyn kinase is highly expressed in oocytes, with inhibitor and dominant-negative studies suggesting a role in the signal transduction events during egg activation. The purpose of the present investigation was to test the hypothesis that Fyn is required for calcium signalling, meiosis resumption and pronuclear congression using the Fyn-knockout mouse as a model. Accelerated breeding studies revealed that Fyn-null females produced smaller litter sizes at longer intervals and exhibited a rapid decline in pup production with increasing age. Fyn-null females produced a similar number of oocytes, but the frequency of immature oocytes and mature oocytes with spindle chromosome abnormalities was significantly higher than in controls. Fertilised Fyn-null oocytes frequently (24%) failed to undergo pronuclear congression and remained at the one-cell stage. Stimulation with gonadotropins increased the number of oocytes ovulated, but did not overcome the above defects. Fyn-null oocytes overexpressed Yes kinase in an apparent effort to compensate for the loss of Fyn, yet still exhibited an altered pattern of protein tyrosine phosphorylation. In summary, Fyn-null female mice exhibit reduced fertility that appears to result from actin cytoskeletal defects rather than calcium signalling. These defects cause developmental arrest during oocyte maturation and pronuclear congression. PMID- 20591333 TI - Characterisation of endometrial gene expression and metabolic parameters in beef heifers yielding viable or non-viable embryos on Day 7 after insemination. AB - The aim of the present study was to compare the hormonal and metabolic characteristics and endometrial gene expression profiles in beef heifers yielding either a viable or degenerate embryo on Day 7 after insemination as a means to explain differences in embryo survival. Oestrus was synchronised in cross-bred beef heifers (n = 145) using a controlled internal drug release (CIDR) prostaglandin protocol. Heifers (n = 102) detected in standing oestrus (within 24 48 h after CIDR removal) were inseminated 12-18 h after detection of oestrus (Day 0) with frozen-thawed semen from a single ejaculate of a bull with proven fertility. Blood samples were collected from Day 4 to Day 7 after oestrus to measure progesterone (on Days 4, 5 and 7), insulin and insulin-like growth factor (IGF)-I (on Days 4 and 6) and urea (on Day 7) concentrations. All animals were killed on Day 7. Uterine pH was determined at the time of death. Animals from which an embryo was recovered were classified as either having a viable embryo (morula/blastocyst stage; n = 32) or a retarded embryo (arrested at the two- to 16-cell stage; n = 19). In addition, 14 single-celled unfertilised oocytes were recovered, giving an overall recovery rate of 64%. There was no significant difference in the blood parameters determined or uterine pH at the time of death between heifers with either a viable or retarded embryo. The relative abundance of nine transcripts (i.e. MOGAT1, PFKB2, LYZ2, SVS8, UHRF1, PTGES, AGPAT4, DGKA and HGPD) of 53 tested in the endometrial tissue differed between heifers with a viable or retarded embryo. Both LYZ2 and UHRF1 are associated with regulation of the immune system; PFKFB2 is a mediator in glycolysis; MOGAT, AGPAT4 and DGKA belong to the triglyceride synthesis pathway; and PTGES and HGPD belong to the prostaglandin pathway. Both these metabolic pathways are important for early embryonic development. In conclusion, retarded embryo development in the present study was not related to serum progesterone, IGF-I, insulin or urea concentrations, nor to uterine pH at the time of death. However, altered expression of genes involved in the prostaglandin and triglyceride pathways, as well as two genes that are closely associated with the regulation of immunity, in the endometrium may indicate a uterine component in the retardation of embryo development in these beef heifers. PMID- 20591334 TI - Treatment of ovine oocytes with caffeine increases the accessibility of DNase I to the donor chromatin and reduces apoptosis in somatic cell nuclear transfer embryos. AB - Caffeine treatment of ovine oocytes increases the activity of maturation promoting factor (MPF) and mitogen-activated protein kinases (MAPKs) and, in somatic cell nuclear transfer (SCNT) embryos, increases the frequency of nuclear envelope breakdown (NEBD) and premature chromosome condensation (PCC). At the blastocyst stage, caffeine-treated SCNT embryos have increased cell numbers. One explanation for this is that NEBD and PCC release chromatin-bound somatic factors, allowing greater access of oocyte factors involved in DNA synthesis and nuclear reprogramming to donor chromatin. This could advance DNA replication and cleavage in the first cell cycle, resulting in increased cell numbers. Alternatively, increased MAPK activity may affect localisation of heat shock proteins (HSPs) and reduce apoptosis. To investigate these possibilities, we investigated chromatin accessibility, the timing of DNA synthesis and first cleavage, the localisation of HSP27 during early development and the frequency of apoptotic nuclei at the blastocyst stage. Compared with control SCNT (non caffeine treatment), caffeine treatment (10 mM caffeine for 6 h prior to activation) increased the accessibility of DNase I to donor chromatin (P < 0.05 at 1.5 h post activation (h.p.a.)), advanced DNA synthesis (43.5% v. 67.6%, respectively; P < 0.01 at 6 h.p.a.) and first cleavage (27.3% v. 40.5% at 20 h.p.a., respectively) and increased nuclear localisation of HSP27. Although development to the blastocyst stage was not affected, caffeine increased total cell numbers (98.5 v. 76.6; P < 0.05) and reduced the frequency of apoptotic nuclei (11.27% v. 20.3%; P < 0.05) compared with control SCNT group. PMID- 20591335 TI - Zebrafish (Danio rerio) and the egg size versus egg number trade off: effects of ration size on fecundity are not mediated by orthologues of the Fec gene. AB - Few studies have demonstrated plasticity of egg size within the confines of an egg size-number trade-off in response to trophic conditions in fishes. Moreover, the physiological mechanisms that govern this plasticity are not known. Growth differentiation factor 9 (Gdf9) and bone morphogenetic factor 15 (Bmp15) are oocyte-specific factors implicated in follicular growth and ovulation in mammals. In order to investigate whether expression levels of these genes were correlated with ration-dependent changes in fecundity in fish, zebrafish (Danio rerio) were subjected to four different feeding regimens. Counts of spawned eggs or vitellogenic follicles were used to estimate fecundity, whereas quantitative polymerase chain reaction analyses were performed to determine Gdf9 and Bmp15 mRNA levels in response to changes in ration size. Both relative fecundity and gonadosomatic index increased significantly with increased ration size, whereas egg size and hatching rate decreased significantly. No significant differences in Gdf9 or Bmp15 transcript abundance were evident between feeding regimens, suggesting that these growth factors do not govern fecundity in fish. However, favourable trophic conditions markedly affected follicle or egg size and number, with important implications for downstream egg quality and survival. PMID- 20591336 TI - Lineage-specific expression of heterochromatin protein 1gamma in post-compaction, in vitro-produced bovine embryos. AB - Heterochromatin protein 1gamma (HP1gamma) is a highly conserved regulator of euchromatic and heterochromatic gene expression. Mammalian HP1gamma is essential for both successful preimplantation embryo development and maintenance of pluripotency in embryonic stem cells in vitro. Here, we describe HP1gamma protein localisation in matured (MII) bovine oocytes and IVF preimplantation embryos at defined developmental stages. HP1gamma is expressed in post-compaction embryos in a highly lineage-specific pattern. In embryonic stages preceding the maternal to embryonic transition (MET), HP1gamma protein was primarily cytoplasmic, whereas in 8-16-cell embryos (post MET), HP1gamma was primarily nuclear. Lineage-specific patterns of HP1gamma protein localisation become evident from compaction, being restricted to peripheral, extraembryonic cells at the morula and blastocyst stages (Days 7-9). Surprisingly, we detected HP1gamma mRNA in both embryonic and extraembryonic cells in blastocysts by fluorescence in situ hybridisation. In trophectoderm cells, HP1gamma protein was localised in specific patterns at the mitotic and interphase stages of the cell cycle. These results demonstrate lineage- and cell cycle-specific patterns of HP1gamma protein localisation in the post-compaction, preimplantation bovine embryo and raise interesting questions about the role of HP1gamma in early embryo development. PMID- 20591337 TI - Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes. AB - Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes. PMID- 20591338 TI - Effects of histone hyperacetylation on the preimplantation development of male and female bovine embryos. AB - Trichostatin A (TSA) induces histone hyperacetylation by inhibiting histone deacetylases and consequently increasing gene expression. The hypothesis was that TSA supplementation during the in vitro culture (IVC) of bovine embryos would increase the blastocyst rate, particularly in low-quality and female embryos. Oocytes were fertilised separately with X and Y spermatozoa and, 70 h after IVF, the IVC medium was supplemented with 5 nM and 15 nM TSA for 48 or 144 h. Incubation of female embryos with 5 nM and 15 nM TSA resulted in similar increases in acetylated histone H3K9 levels. However, to see comparable effects on acetylated histone H3K9 levels in male embryos, the culture medium needed to be supplemented with 15 nM TSA (as opposed to 5 nM TSA for female embryos). Treatment of male and female embryos with 5 nM TSA for 48 h or female embryos with 5 nM for 144 h had no effect on blastocyst rates, although 15 nM TSA compromised embryonic development. The terminal deoxyribonucleotidyl transferase mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay revealed increased apoptosis in female embryos treated with 5 nM TSA for 144 h, as well as in male and female embryos treated with 15 nM TSA for 48 h, but this increase in apoptosis was not observed in low-quality embryos. The results of the present study suggest that TSA treatment promotes histone hyperacetylation, but has no beneficial effects on the in vitro production of male and female bovine embryos during preimplantation development. PMID- 20591340 TI - Polypharmacy in general practice. AB - INTRODUCTION: Polypharmacy increases the risk of side effects and interactions. We quantified the prevalence of major polypharmacy (MPP) in a Danish county with 236,000 inhabitants, invited general practitioners (GPs) to participate in a quality improvement project and discussed the medication of 10-20 MPP patients selected by the participating GPs. MATERIAL AND METHODS: This was a prospective registry study of all prescriptions of subsidized drugs in the third quarter of 2005 for all inhabitants living in Roskilde County, Denmark. An audit was performed of the prescriptions of 220 MPP patients selected by the GPs based on a list of each MPP patient's medications. RESULTS: MPP patients constituted 2.1% of the county's population. GPs demonstrated a strong interest in auditing prescriptions. A large share of the patients selected by the GPs was treated with drugs which were no longer indicated, or with drugs with a doubtful indication. CONCLUSIONS: MPP compromises the GP's ability to manage medication of individual patients. Systematic audit of the total medication of patients should be introduced. PMID- 20591339 TI - Reconstruction using free jejunal transfer after resection of cancer of the upper oesophagus. AB - INTRODUCTION: Treatment of cancer of the upper part of the oesophagus is challenging. Even after intended curative treatment, less than half of the patients are alive after five years. This retrospective study evaluates all the patients who had the upper oesophagus reconstructed by use of a free jejunal transfer following cancer resection from February 2000 to May 2008 at the University Hospital of Aarhus. MATERIAL AND METHODS: Twenty patients aged 46-75 years were included. In all 20 cases, the diagnosis was squamous cell carcinoma, T3 or T4. All patients suffered from severe dysphagia prior to surgery. The median follow-up time was 23 months at 31 January 2010. RESULTS: No perioperative mortality was experienced. Thirteen patients are now dead; nine due to the cancer of the oesophagus and four due to other causes. The median survival time of the 13 diseased patients was 15.3 months. The seven patients who remain alive have a median survival time of 40.2 months. None of these patients have shown signs of recurrence of the oesophageal cancer. All the patients regained their capacity to swallow and thereby increased their quality of life. No complications were experienced in relation to the abdominal procedure of harvesting the jejunal transfer. Three patients developed a fistula and in one case this required minor surgery. Eight patients needed to have a dilatation procedure performed. CONCLUSION: Reconstruction of the oesophagus with a free jejunal transfer is a suitable treatment for selected patients with cancer in the upper oesophagus. PMID- 20591341 TI - Care principles at four fast-track arthroplasty departments in Denmark. AB - INTRODUCTION: The goal of this study was to describe the logistic and clinical set-up at four Danish arthroplasty departments offering fast-track surgery. MATERIAL AND METHODS: Based on the National Patient Registry's information on patients who have undergone total hip and knee arthroplasty, four departments were chosen for evaluation in accordance with the following inclusion criteria: documented fast-track surgery with written care plans, a surgical volume of > 450 arthroplasties and short length of stay (LOS) (< 5 days). RESULTS: The mean LOS ranged from 2.8 to 3.9 days. Logistic features included homogeneous entities, regular staff, high level of continuity, preoperative information including intended LOS, admission on the day of surgery and functional discharge criteria. The clinical features were both intraoperative (spinal anaesthesia, local infiltration analgesia, plans for fluid therapy, small standard incisions, no drains, compression bandages and cooling) and postoperative (deep venous thrombosis prophylaxis starting 6-8 hours postoperatively, multimodal opioid sparing analgesia, early mobilisation and discharge when functional criteria were met) facilitating early rehabilitation and discharge. CONCLUSION: The logistic set-up at the four departments was almost identical. The basic care prerequisites to pooling the patients from these four departments were in place. Future studies will include outcomes as well as safety aspects of this set-up. PMID- 20591342 TI - Toward more uniform conflict disclosures: the updated ICMJE conflict of interest reporting form. PMID- 20591343 TI - Pathophysiology and clinical implications of peroperative fluid management in elective surgery. AB - The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome studies. In laparoscopic cholecystectomy, we have found "liberal" crystalloid administration ( approximately 3 liters) to improve perioperative physiology and clinical outcome, which has implication for fluid management in other laparoscopic procedures such as laparoscopic fundoplication, laparoscopic repair of ventral hernia, hysterectomy etc., where 2-3 liters crystalloid should be administered based on the present evidence. That equal amounts of fluid caused adverse physiologic effects in healthy volunteers indicates that addition of the surgical trauma per se increases fluid requirements. Volume kinetic analysis applied 4 hours postoperatively was not able to detect the presence of either overhydration or hypovolemia regardless of the administered fluid volume intraoperatively. In knee arthroplasty a approximately 4 vs. approximately 2 liters crystalloid-based fluid regimen lead to significant hypercoagulability (although with unknown clinical implications), but no over-all differences in functional recovery. Dehydration caused by bowel preparation leads to functional hypovolemia and the deficits should be corrected, in particular in elderly patients, where preoperative intravenous fluid substitution of approximately 2-3 liters crystalloid is recommended. We did not find thoracic epidural anesthesia to be accompanied by intravascular fluid mobilization. In major (colonic) surgery with a standardized multimodal rehabilitation regimen, over-all functional recovery was not affected with a "liberal" ( approximately 5 liters) vs. "restrictive" 1.5 liter crystalloid-based regimen, however based on three anastomotic leakages in the "restrictive" group, it may be hypothesized that a too "restrictive" fluid administration strategy could be detrimental in patients with anastomoses and need further evaluation. A systematic review concluded that present evidence does not allow final recommendations on which type of fluid to administer in elective surgery. Based on the current evidence, administration of < 5 liters intravenous fluid without specific indication in major surgical procedures should be avoided, while administration of < 1.5 liters in patients with anastomoses may not be recommended, an issue needing clarification in large-scale clinical studies. Finally, we have demonstrated that the conduction of double-blinded randomized trials on fluid management with postoperative outcomes is feasible. PMID- 20591344 TI - Human-like atherosclerosis in minipigs: a new model for detection and treatment of vulnerable plaques. AB - Advanced atherosclerosis, through thrombosis, leads to ischemic heart disease and ischemic stroke, the leading causes of death and disability worldwide. Advanced atherosclerosis and imaging of atherosclerosis are the focus of this dissertation with particular emphasis on the vulnerable plaque and vulnerable plaque detection. Aspects of advanced atherosclerosis and the vulnerable plaque in humans are described along with the basis for the selected minipig models and methods for atherosclerosis acceleration used. The overall aims of the studies were to develop an animal model of advanced atherosclerosis with human like vulnerable plaque morphology and use this animal model to test an imaging modality aimed at vulnerable plaque detection. The first aim is addressed in 3 papers, where accelerated plaque development in the coronary and carotid arteries is investigated in down sized Rapacz pigs. Down-sized Rapacz pigs are minipigs with familial hypercholesterolemia caused by a mutation in the low density lipoprotein receptor. Paper 1 describes the lipid profile in the down-sized Rapacz on chow and atherogenic diets and spontaneously developed and balloon accelerated coronary plaque with a morphology that resembles the morphology of human vulnerable plaque. Paper 2 describes vein graft disease in internal jugular vein grafts inserted into the common carotid artery. Plaques with necrotic cores were found in oversized vein grafts only indicating an effect of flow and shear stress on plaque development. Paper 3 describes the effects of wall shear stress on local plaque development in surgically stenosed common carotid arteries in the down-sized Rapacz pigs. This study indicated that the combination of low and oscillatory wall shear stress was needed for development of advanced plaque. In paper 4, we interrogated coronary lesions in the down-sized Rapacz with a commercially available diagnostic tool VH IVUS. It is claimed that VH IVUS can characterize the tissue components that constitute plaque reliably. However, we found that VH IVUS does not reliably assess the most important plaque component of all, i.e. the necrotic core. In conclusion, we developed an animal model of advanced atherosclerosis with human like vulnerable plaque morphology. The usefulness of this animal model was demonstrated in a study testing an imaging modality aimed at vulnerable plaque detection in humans. PMID- 20591346 TI - Changes. PMID- 20591345 TI - Incretin hormones and beta cell function in chronic pancreatitis. AB - Type 2 diabetes mellitus (T2DM) has been shown to be characterised by an almost abolished incretin effect. The incretin effect refers to the phenomenon of oral glucose eliciting a higher insulin response than intravenous glucose at identical plasma glucose profiles. It is conveyed by the two insulinotropic incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 and GIP are secreted from the small intestines in response to ingestion of nutrients. The incretin defect of T2DM has been characterised by a virtually lost insulinotropic effect of GIP. It is unknown whether the incretin defect is a primary event leading to T2DM or arises as a consequence of the diabetic state. To investigate this we studied patients with chronic pancreatitis (CP). Over time, CP leads to secondary diabetes mellitus (DM). If patients with CP and secondary DM exhibit the characteristic type 2 diabetic incretin deficiencies and patients with CP and normal glucose tolerance are normal in that regard, it is more likely that these deficiencies are consequences of the diabetic state rather than primary events leading to T2DM. On the other hand, if incretin physiology is preserved independently of the endocrine status of patients with CP, the incretin defect could represent a primary pathogenetic defect. Three protocols have been employed to investigate this. In a study investigating postprandial incretin responses in 8 patients with CP and exocrine pancreatic insufficiency, with and without pancreatic enzyme supplementation (PES), we observed preserved incretin responses as compared to matched healthy subjects; and, further, that PES increased postprandial incretin responses in these patients. This suggests not only that the secretion of incretin hormones is regulated by the mere presence of nutrients in the small intestine, but also that the assimilation of such nutrients is involved, as well. Furthermore, we gauged the incretin effect in 8 patients with CP and normal glucose tolerance and in 8 patients with CP and secondary DM. Eight healthy subjects and 8 patients with T2DM were studied for comparison. The incretin effect was shown to be preserved in normal glucose tolerant patients with CP, whereas it was strongly reduced in patients with CP and secondary DM, suggesting the incretin defect to be a consequence of the diabetic state. Lastly, we investigated the insulinotropic effect of the incretin hormones in 8 patients with CP and normal glucose tolerance and in 8 patients with secondary DM, and observed that patients with CP and secondary DM exhibit an impaired insulinotropic effect of GIP, and that this most likely occurs as a consequence of the diabetic state. In conclusion, we suggest that: 1) the postprandial secretion of incretin hormones is preserved among patients with CP; 2) assimilation of nutrients stimulates secretion of GIP and GLP-1; and 3) the characteristic incretin deficiencies of T2DM most likely are consequences of a deteriorating glucose homeostasis, rather than primary events leading to T2DM. PMID- 20591347 TI - Heart rate nonlinear dynamics during sudden hypoxia at 8230 m simulated altitude. AB - OBJECTIVE: Acute hypobaric hypoxia is associated with autonomic changes that bring a global reduction of linear heart rate variability (HRV). Although changes in nonlinear HRV can be associated with physiologic stress and are relevant predictors of fatal arrhythmias in ischemic heart disease, to what extent these components vary in sudden hypobaric hypoxia is not known. METHODS: Twelve military pilots were supplemented with increasing concentrations of oxygen during decompression to 8230 m in a hypobaric chamber. Linear and nonlinear HRV was evaluated at 8230 m altitude before, during, and after oxygen flow deprivation. Linear HRV was assessed through traditional time-domain and frequency-domain analysis. Nonlinear HRV was quantified through the short-term fractal correlation exponent alpha (alphas) and the Sample Entropy index (SampEn). RESULTS: Hypoxia was related to a decrease in linear HRV indexes at all frequency levels. A non significant decrease in alphas (basal, 1.39 +/- 0.07; hypoxia, 1.11 +/- 0.13; recovery, 1.41 +/- 0.05; P = .054) and a significant increase in SampEn (basal, 1.07 +/- 0.11; hypoxia, 1.45 +/- 0.12; recovery, 1.43 +/- 0.09; P = .018) were detected. CONCLUSIONS: The observed pattern of diminished linear HRV and increased nonlinear HRV is similar to that seen in subjects undergoing heavy exercise or in patients with ischemic heart disease at high risk for ventricular fibrillation. PMID- 20591348 TI - Plasma proANP1-98 response during high altitude stress: effect of age and ethnicity. AB - OBJECTIVE: Acclimatization to high altitude (HA) is accompanied by decrease in plasma atrial natriuretic peptide (ANP). On the other hand, circulating levels of the hormone are known to be influenced by age and ethnicity. The impact of these factors on ANP response during prolonged HA exposure remains unexplored. Hence, this study was conducted to examine possible age and ethnic variation in plasma proANP(1-98) levels in men after 3 to 4 weeks at HA. METHODS: Lowlanders (LL) were studied at sea level (SL) and after 3 to 4 weeks at an altitude of approximately 4500 m. The LL group comprised Rajput (n = 48), Gorkha (n = 40), and South Indian (n = 43) ethnicities. Another group of HA natives (Ladakhi, n = 40) were studied at approximately 4500 m only. Subjects were between 20 and 50 years of age. Estimation of plasma proANP(1-98) and biochemical, hematologic, and physiologic evaluation was done. RESULTS: In LL at HA, proANP(1-98) levels decreased (P < .001); plasma arginine vasopressin decreased (P < .05 in Rajputs and South Indians); and total protein, hemoglobin, and hematocrit increased (P < .05). Heart rate increased (P < .05), whereas arterial oxygen saturation decreased (P < .05) in all LL at HA. Ethnicity but not age variation in proANP(1 98) was observed under HA stress. In HA natives, plasma proANP(1-98) was higher than LL at HA and did not exhibit any age variation. CONCLUSIONS: Plasma proANP(1 98) levels, reflecting medium-term ANP secretion, decrease during prolonged exposure to HA in LL. This is due to diuresis leading to plasma volume reduction that occurs during the acclimatization process. Ethnicity but not age variation is associated with plasma proANP(1-98) under HA stress. PMID- 20591349 TI - Constitutional and behavioral risk factors for chilblains: a case-control study from Pakistan. AB - OBJECTIVES: To study constitutional and behavioral risk factors for chilblains in patients at Abbottabad and Sialkot, Pakistan. METHODS: One hundred patients and matched controls completed a single-page, close-ended questionnaire which included demographic data and questions related to possible constitutional and behavioral risk factors for chilblains. Computer program SPSS-10 was used to manage and analyze the data. Risk factors were identified statistically by determining odds ratios and 95% confidence intervals using multivariate analysis. RESULTS: There were an equal number of male and female respondents in each group. Age of the patients and controls ranged from 2 to 80 years with a mean of 24.51 +/- 16.02. Twenty-six patients and 3 controls had a positive family history for chilblains (odds ratio = 9.33); 42 patients and 14 controls reported a history of constipation (odds ratio = 2.69); 32 patients and 8 controls had a history of either numbness or tingling of fingers or toes (odds ratio = 2.93); 55 patients and 45 controls led sedentary lifestyles (odds ratio = 1.27); 85 patients and 58 controls consumed a low number of cups of tea daily (odds ratio = 3.20); 65 patients and 29 controls frequently washed their hands and/or feet (odds ratio = 4.93); and 56 patients and 33 controls had occasional sun exposure during winter months (odds ratio = 2.08). CONCLUSION: Significant risk factors for the development of chilblains for people at Abbottabad and Sialkot included a history of chilblains in first-degree relatives, numbness and tingling sensations of fingers or toes, frequent hand or feet washing, and lower tea consumption during winter months. PMID- 20591350 TI - Stress hormone responses to an ultraendurance race in the cold. AB - OBJECTIVE: Physical stress (exercise and/or environmental) activates the sympathetic-adrenal-medullary (SAM) and hypothalamic-pituitary-adrenocortical (HPA) axes. The combination of ultraendurance exercise in the cold presents a unique summated stress to the body. The purpose of this study was to assess the stress hormone response in runners, cyclists, and skiers participating in a 161 km ultraendurance race on a snow-packed course in the Alaskan wilderness. METHODS: Forty-four athletes (20 runners, 17 cyclists, 7 skiers) competed on the same course of snow-machine trails and ice roads with each athlete carrying 7 kg of mandatory equipment. Pre-race weight and blood samples were collected 2 days prior to the race start. Post-race measurements were made within 15 minutes of race finish. Hematocrit was measured, and blood samples were analyzed for levels of norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol. RESULTS: Runners lost significant weight (-1.74 kg +/- 1.29) pre-race to post race. Hematocrit was maintained, and plasma volume increased minimally. Norepinephrine increased significantly pre-race (279.9 pg/mL +/- 356.9) to post race (691.7 pg/mL +/- 422.6) with no difference among divisions. Epinephrine did not change significantly during the race. Adrenocorticotropic hormone (2.40 pg/mL +/- 2.40 to 19.04 pg/mL +/- 45.38) increased significantly with no difference among divisions. Cortisol increased significantly pre-race (12.03 microg/dL +/- 5.66) to post-race (26.69 microg/dL +/- 5.77), and post-race cortisol was significantly higher in runners vs skiers. CONCLUSIONS: These data suggest activation of both the SAM and HPA axes from an ultraendurance race in the cold and reveal the degree of stress hormone responses to this exhausting bout of exercise. PMID- 20591351 TI - Triaging multiple victims in an avalanche setting: the Avalanche Survival Optimizing Rescue Triage algorithmic approach. AB - As winter backcountry activity increases, so does exposure to avalanche danger. A complicated situation arises when multiple victims are caught in an avalanche and where medical and other rescue demands overwhelm resources in the field. These mass casualty incidents carry a high risk of morbidity and mortality, and there is no recommended approach to patient care specific to this setting other than basic first aid principles. The literature is limited with regard to triaging systems applicable to avalanche incidents. In conjunction with the development of an electronic avalanche rescue training module by the Canadian Avalanche Association, we have designed the Avalanche Survival Optimizing Rescue Triage algorithm to address the triaging of multiple avalanche victims to optimize survival and disposition decisions. PMID- 20591352 TI - Sensationalistic journalism and tales of snakebite: are rattlesnakes rapidly evolving more toxic venom? AB - Recent reports in the lay press have suggested that bites by rattlesnakes in the last several years have been more severe than those in the past. The explanation, often citing physicians, is that rattlesnakes are evolving more toxic venom, perhaps in response to anthropogenic causes. We suggest that other explanations are more parsimonious, including factors dependent on the snake and factors associated with the bite victim's response to envenomation. Although bites could become more severe from an increased proportion of bites from larger or more provoked snakes (ie, more venom injected), the venom itself evolves much too slowly to explain the severe symptoms occasionally seen. Increased snakebite severity could also result from a number of demographic changes in the victim profile, including age and body size, behavior toward the snake (provocation), anatomical site of bite, clothing, and general health including asthma prevalence and sensitivity to foreign antigens. Clinical management of bites also changes perpetually, rendering comparisons of snakebite severity over time tenuous. Clearly, careful study taking into consideration many factors will be essential to document temporal changes in snakebite severity or venom toxicity. Presently, no published evidence for these changes exists. The sensationalistic coverage of these atypical bites and accompanying speculation is highly misleading and can produce many detrimental results, such as inappropriate fear of the outdoors and snakes, and distraction from proven snakebite management needs, including a consistent supply of antivenom, adequate health care, and training. We urge healthcare providers to avoid propagating misinformation about snakes and snakebites. PMID- 20591353 TI - Ophidism by the green palmsnake. AB - The author describes his experience following 2 bites to his hand by the same green palmsnake (Philodryas viridissimus) on the same day, and reviews the literature on bites from rear-fanged species of the genus Philodryas. Though this genus has long been thought to include the most venomous colubrid snakes in the Americas, the author's bites were relatively asymptomatic. Fatalities caused by Philodryas seem to be lacking in the primary literature, but mild to moderate symptoms do result from envenomations by at least 2 species. Medical researchers are urged to obtain accurate species identifications and to carefully report symptoms and fatalities from bites of colubrid snakes. PMID- 20591354 TI - Liver transplantation in a patient with pulmonary hypertension at high altitude. AB - Chronic hypoxia at high altitude stresses many of the body's homeostatic mechanisms. As a consequence, the body develops alveolar hypoxia, hypoxemia, and polycythemia, which in turn causes vasoconstriction, pulmonary hypertension, and an increased risk of atherothrombotic complications. We report a successful liver transplantation in a patient with pulmonary hypertension who lives 4500 m above sea level. Pulmonary hypertension and hypercoagulable state induced by chronic hypoxia at high altitude may increase the risk of cardiopulmonary complication and perioperative mortality. The patient was discharged in good condition with normal liver function at the 34th postoperative day. After 41 months of follow up, the patient is alive and well with a continued normalization of hepatic function and is continuing to live at 4500 m above sea level. PMID- 20591355 TI - Snakebite during pregnancy: a literature review. AB - OBJECTIVE: To review reported bites by venomous snakes in pregnant women. METHODS: This is a review of Medline/PubMed articles on venomous snakebites occurring during pregnancy reported in the English literature from 1966 to May 2009. RESULTS: Two hundred thirteen venomous snakebites were reported in pregnant women. The overall case-fatality rate in the pregnant females was approximately 4%, and the fetal loss rate was approximately 20%. CONCLUSIONS: Although rare, venomous bites and stings during pregnancy may have a significant adverse effect on the fetus as well as the mother. PMID- 20591356 TI - Intoxication with a ramp (Allium tricocca) mimicker. False hellebore (Veratrum viride) ingestion. PMID- 20591357 TI - Classroom and reality: what should we teach in wilderness first aid courses? PMID- 20591358 TI - Wilderness first aid training. PMID- 20591359 TI - Response to "Wilderness first aid: is there an 'industry standard'?". PMID- 20591361 TI - Response to "Wilderness first aid: is there an 'industry standard'?". PMID- 20591362 TI - Wilderness first aid and sports medicine. PMID- 20591364 TI - Trekker behavior as one indicator of AMS knowledge. PMID- 20591366 TI - Work at high altitude after coronary stenting: safe? PMID- 20591367 TI - In tribute to Charlie Houston. PMID- 20591369 TI - Sidecountry rescue---who should respond to ski resort out-of-bounds rescues? PMID- 20591368 TI - Search and rescue activity on Denali, 1990 to 2008. PMID- 20591370 TI - Search and rescue activity on Denali, 1990 to 2008. AB - OBJECTIVE: To describe search and rescue activity performed by the National Park Service (NPS) on Denali, the highest point in North America. METHODS: A retrospective review was performed of all search and rescue (SAR) operations by the NPS from 1990 to 2008. Descriptive analysis was used to describe these cases as well as chi-square and logistic regression analysis to determine which mountaineers were more likely to require a rescue. RESULTS: During the study period, 1.16% of all Denali climbers required NPS SAR response. The majority of medical cases (68.9%) were due to high altitude and cold injuries, and the majority of traumatic cases (76.2%) resulted from a fall. Mountaineers that attempt routes other than the standard West Buttress route are more likely to require rescue. Climbers are 3% more likely to require a rescue with each year of advancing age. Similarly, mountaineers from Asia are more likely to require a rescue (odds ratio = 4.1), although this trend has diminished in the past decade. CONCLUSIONS: Mountaineers and rescuers should educate themselves on the environmental, logistical, and medical origins of Denali rescues. Certain demographic groups on certain routes are more likely to require a rescue on Denali. Rescuers should be aware of these groups and have the knowledge and capabilities to care for the medical issues that are common on SAR responses. PMID- 20591371 TI - End-tidal partial pressure of carbon dioxide and acute mountain sickness in the first 24 hours upon ascent to Cusco Peru (3326 meters). AB - OBJECTIVE: To explore the association of end-title partial pressure (Petco(2)) and oxygen saturation (Spo(2)) with the development of AMS in travelers rapidly ascending to Cusco, Peru (3326 m). METHODS: Using the 715 TIDAL WAVE Sp handheld, portable capnometer/oximeter, we measured Spo(2) and Petco(2) in 175 subjects upon ascent to Cusco, Peru (3326 m) from Lima (sea level) (a mean time of 3.9 hours.) Symptoms of AMS were recorded at the same initial time on arrival to altitude and 24 hours later using the Environmental Symptoms Questionnaire (ESQ). RESULTS: This study showed that no subjects with the lowest Petco(2) of 23 to 30 mm Hg had AMS (P <.044). The data also demonstrate that subjects with a higher Petco(2) (36-40 mm Hg) and lower Sao(2) (72%-86%) have a higher incidence of AMS. CONCLUSION: The most important finding of this study is that Petco(2) upon ascent was found to have a more significant effect than Spo(2) on a subject's ultimate ESQ score. This study demonstrates that those individuals with a brisk ventilatory response upon ascent to moderate altitude, as measured by Petco(2), did not develop AMS, whereas a blunted ventilatory response, as reflected in the highest Petco(2), was related to the subsequent development of AMS. PMID- 20591372 TI - Vipera berus bites in the Region of Southwest Poland--a clinical analysis of 26 cases. AB - OBJECTIVE: Vipera berus is the only naturally occurring venomous snake in Poland. Its venom is primarily vasculotoxic and evokes both local and systemic findings. The aim of the study was to review a series of clinical cases of V berus bites occurring in southwest Poland. METHODS: The charts of 26 patients (age range, 16 66 years; mean, 42 years) hospitalized with V berus bites were retrospectively analyzed using a data collection tool. Demographic and clinical data were extracted. RESULTS: The most common local findings of envenomation were edema of the bitten limb with associated extravasations observed in 24 (92.3%) patients, but in only 1 (3.8%) case did the edema spread to the trunk. In 22 (84.6%) cases edema disappeared within 2 weeks after the bite. Systemic disturbances observed in the patients were: shock (1 case), mild transient hypotension (1 case), prolonged hypotension (3 cases), bronchospasm and laryngeal edema (1 case), diarrhea (1 case), transient supraventricular arrhythmias (2 cases), neutrophilic hyperleukocytosis (2 cases), and thrombocytopenia below 50000 cells/microL (5 cases). In 16 patients (61.5%) the envenomation was classified as moderate and this type was predominant. Six cases were classified as severe. No fatal case was reported. Treatment included the administration of specific antivenom in 14 cases (in all severe and half of moderate cases) and symptomatic treatment applied in all cases. CONCLUSIONS: Moderate envenomation prevailed among the patients analyzed in the study. Antivenom treatment is primarily necessary in cases of severe (grade 3) and in some cases of moderate (grade 2) envenomation, especially in patients with persistent or recurring hypotension. PMID- 20591373 TI - Large snake size suggests increased snakebite severity in patients bitten by rattlesnakes in Southern california. AB - OBJECTIVE: To correlate rattlesnake size and other characteristics of envenomation with the severity of envenomation. METHODS: We retrospectively reviewed 145 charts of patients bitten by rattlesnakes in Southern California between 1995 and 2004, measuring Snakebite Severity Scores (SSS) and characteristics of envenomation that might be correlated with snakebite severity, including rattlesnake size, rattlesnake species, patient size, and anatomic location of the bite. Outcomes measured included SSS, complications of envenomation, number of vials of antivenom used, and length of hospital stay. RESULTS: Of the patients bitten by rattlesnakes, 81% were men, and 79% of bites were on the upper extremities. Fifty-five percent of bites were provoked by the patient, and 44% were unprovoked. Neither location of snakebite nor provocation of snakebite affected the SSS. Only 1 patient had a snakebite without envenomation, and only 1 patient died from envenomation. Rattlesnake size was positively correlated with SSS, and SSS was positively correlated with the number of vials of antivenom used and with the length of hospital stay. Rattlesnake species and patient mass did not affect SSS. CONCLUSIONS: Larger rattlesnakes cause more severe envenomations, which contradicts popular belief. PMID- 20591374 TI - Frostbite in a Sherpa. AB - Frostbite is frequently seen in high altitude climbers. Many Sherpas, members of an ethnic community living high in the Himalayas in Nepal, help the climbers as a guide or an assistant. They often seem to undertake few precautionary measures thus suffer more from frostbite. A young Sherpa, who had reached the top of Mt Kanchenjunga in March 2009, suffered from deep frostbite in his fingers. Fortunately, he recovered well with generous treatment. Though there is no evidence whether Sherpas are more or less prone to frostbite, simple techniques for adequate prevention of hypoxia, hypothermia and dehydration will benefit any climber to the high altitudes. PMID- 20591375 TI - Bites caused by giant water bugs belonging to Belostomatidae family (Hemiptera, Heteroptera) in humans: a report of seven cases. AB - We report 7 cases of patients bitten by giant water bugs, large predatory insects belonging to the Belostomatidae family (Hemiptera, Heteroptera). These insects have toxic saliva capable of provoking intense pain and paralysis in vertebrates. Victims experienced intense, excruciating pain and 1 manifested hypoesthesia in the forearm. Bites by Belostomatidae are often reported by clinicians working in areas where these insects live, but there are no detailed case reports in the medical literature. There are no specific treatment modalities known to be effective, making prevention an important strategy. PMID- 20591376 TI - Ocular toxicity associated with indirect exposure to African spitting cobra venom. AB - Direct ocular inoculation with African spitting cobra (Naja nigricollis) venom in the United States is uncommon, especially in an urban setting, but can lead to serious acute and chronic ocular injury depending on the extent of exposure. We report 2 cases of indirect ocular inoculation with venom from an African spitting cobra, manifesting as periocular soft tissue swelling, extensive conjunctivitis, and corneal epithelial erosion. Both of the reported cases involve young male patients who received prompt emergency evaluation and treatment including copious irrigation of the ocular surface, followed by close monitoring by an ophthalmologist resulting in excellent outcomes with minimal visually significant ocular sequelae. PMID- 20591377 TI - The ultrasound identification of simulated long bone fractures by prehospital providers. AB - OBJECTIVE: In austere environments, patient management decisions are often limited by obtainable resources. Portable ultrasound may allow for the detection of fractures when imaging modalities such as radiography are unavailable. We used a simulation training model in a pilot study to examine the ability of emergency medical technicians (EMTs) to detect the presence or absence of a variety of simulated fracture patterns with portable ultrasound. METHODS: The fracture simulation model is composed of a mechanically fractured bare turkey leg bone housed in a shallow container within a completely opaque gelatin solution. Five different fracture patterns were created. Twenty EMTs sonographically evaluated these models with a portable ultrasound device to determine the presence or absence of a fracture. RESULTS: EMTs correctly identified the presence or absence of a fracture in the no fracture, transverse fracture, and oblique fracture models 95% of the time. They always correctly identified the presence of a fractured model when assessing the comminuted and segmental fracture models. Across all fracture patterns, a final detection sensitivity of 97.5% (95% confidence interval [CI]: 94.1%-100.0%) and a specificity of 95.0% (95% CI: 85.4% 100.0%) were observed. CONCLUSIONS: Using portable ultrasound, EMTs correctly detected the presence or absence of simulated long bone fractures with a high degree of sensitivity and specificity. Future studies may evaluate the ability of other groups to use ultrasound to assist in the diagnosis of fractures and examine the clinical impact of this skill in environments where conventional imaging modalities are limited or unavailable. PMID- 20591378 TI - Detection and management of hypothermia at a large outdoor endurance event in the United kingdom. AB - OBJECTIVE: Optimum detection of hypothermia in athletes during outdoor exposure events remains controversial. The aims of this study were firstly to assess whether temperature readings affected competitor discharge from the treatment station and secondly to assess agreement between oral and tympanic thermometer measurements. METHODS: All competitors treated for symptomatic hypothermia at an outdoor endurance event in the United Kingdom during January 2009 were included. Temperature readings were taken using oral (Digitemp digital oral thermometer) and tympanic (Braun Thermoscan IRT 4520 ExacTemp) thermometers, with a temperature <35 degrees C classifying hypothermia. RESULTS: From 4700 competitors, 64 (1.4%) were treated for symptomatic hypothermia. Of these, 92% were male, the mean age was 26 years, and the mean treatment time was 25 minutes. There was no severe/life-threatening hypothermia, and no competitors required transport to a hospital for hypothermia. At discharge, 19% of competitors were still classed as hypothermic in the oral group and 28% in the tympanic group, despite competitors only being discharged when no longer symptomatic. Oral readings at discharge were significantly lower than tympanic readings (33.8 degrees C [95% CI, 33.2 degrees C to 34.5 degrees C] vs 35.0 degrees C [95% CI, 34.6 degrees C to 35.3 degrees C], respectively, P = .003). CONCLUSIONS: The use of thermometers had a limited role in discharging competitors at this event, who were apparently safely discharged when no longer symptomatic. Treating clinicians and the thermometers did not always agree on whether a patient was hypothermic or not. Oral and tympanic thermometers had poor agreement. Routine thermometer readings at future events may be unnecessary, although screening competitors of concern will remain useful. PMID- 20591379 TI - Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. AB - To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations. PMID- 20591380 TI - Adverse encounters with alligators in the United States: an update. AB - OBJECTIVE: Severe injuries and fatalities can occur from an alligator attack. Encounters with alligators appear to be increasing in the United States. This review provides information from alligator attacks reported in the United States as well as infections that may occur after an alligator bite. METHODS: Telephone interviews were conducted with state wildlife offices in all Southern states in order to collect information on the number of alligator bites, nuisance calls, and the estimated alligator population of each state. Detailed information from alligator attacks in Florida is presented, including basic demographic information on the victims and description of the types of injuries and the activity of the victim at the time of injury. Additional information regarding the size and behavior of the alligator involved in the attack is also provided in many cases. RESULTS: There have been 567 reports of adverse encounters with alligators with 24 deaths reported in the United States from 1928 to January 1, 2009. In addition, thousands of nuisance calls are made yearly and the number of nuisance calls as well as the alligator population is increasing in many states. CONCLUSIONS: Injuries from encounters with alligators may range from minor scratches and punctures to amputations and death. The larger the alligator, the more likely that serious injury will occur. As the human population encroaches on the habitat of the alligator, attacks and nuisance complaints will continue to occur. A uniform reporting system among states should be developed to obtain more complete information on alligator encounters. Guidelines have been developed by many state wildlife officials to reduce adverse encounters with alligators. PMID- 20591381 TI - What's your diagnosis? PMID- 20591382 TI - Advanced wilderness life support education using high-technology patient simulation. AB - OBJECTIVE: (1) To determine if, after using the simulation mannequin SimMan in a wilderness "megacode" exercise, participants believe high-tech simulators are an effective tool for learning wilderness medicine skills. (2) To determine if participants believe high-tech simulation mannequins should be used with more or less frequency in future wilderness medicine exercises. METHODS: After completing a basic training session outlining the capabilities of SimMan and completing a wilderness megacode (defined as a series of progressive conditions that accumulate over time) using SimMan, participants were surveyed to ascertain whether they perceived SimMan to be an effective teaching tool for wilderness medical skills and to determine if they would like SimMan to be used with greater frequency at future wilderness medicine courses. The data were compiled and analyzed using Microsoft Excel. RESULTS: Participants found the wilderness SimMan experience to be an effective tool with an average score of 3.15 on a scale where 4 is most effective and 1 is least effective. Participants also desired to see high-tech simulation more frequently in wilderness courses with a score of 3, on a scale where 4 is more frequently and 1 is less frequently. There was little difference in responses based on previous experience with simulation. CONCLUSIONS: High-tech simulation is an underused tool for wilderness medicine education. Currently, several barriers exist to its implementation in wilderness medicine. Participants in wilderness courses feel it is an effective tool and would like to see it used more frequently. PMID- 20591383 TI - Possible unilateral ultraviolet keratoconjunctivitis during an expedition-length desert race. PMID- 20591384 TI - Rescuing the physical exam. PMID- 20591385 TI - Editor's response to "Rescuing the physical exam". PMID- 20591386 TI - Morbidity related to urban summer camp activities in scholars, Caracas, Venezuela, 2008. PMID- 20591387 TI - A review of lightning safety education for outdoor adventure programs. PMID- 20591388 TI - Higher suicide death rate in rocky mountain states and a correlation to altitude. PMID- 20591389 TI - In response to "The impact of footwear and packweight on injury and illness among long-distance hikers". PMID- 20591392 TI - Use of antivenom in Vipera berus Bites--a comment. PMID- 20591393 TI - UK high altitude research: a report from the Birmingham Medical Research Expeditionary Society (BMRES) altitude research conference, December 4, 2009, held at the Birmingham Medical Institute, United Kingdom. PMID- 20591394 TI - Bubble formation in a quiescent pool of gold nanoparticle suspension. AB - This paper begins with an extensive review of the formation of gas bubbles, with a particular focus on the dynamics of triple lines, in a pure liquid and progresses into an experimental study of bubble formation on a micrometer-sized nozzle immersed in a quiescent pool of aqueous gold nanofluid. Unlike previous studies of triple line dynamics in a nanofluid under evaporation or boiling conditions, which are mainly caused by the solid surface modification due to particle sedimentation, this work focuses on the roles of nanoparticles suspended in the liquid phase. The experiments are conducted under a wide range of flow rates and nanoparticle concentrations, and many interesting phenomena are revealed. It is observed that nanofluids prevent the spreading of the triple line during bubble formation, i.e. the triple line is pinned somewhere around the middle of the tube wall during the rapid bubble formation stage whereas it spreads to the outer edge of the tube for pure water. A unique 'stick-slip' movement of the triple line is also observed for bubbles forming in nanofluids. At a given bubble volume, the radius of the contact line is found to be smaller for higher particle concentrations, but a reverse trend is found for the dynamic bubble contact angle. With the increase of particle concentration, the bubble frequency is raised and the bubble departure volume is decreased. The bubble shape is found to be in a good agreement with the prediction from Young-Laplace equation for given flow rates. The influence of nanoparticles on other detailed characteristics related to bubble growth inside, including the variation of bubble volume expansion rate, the radius of the curvature at the apex, the bubble height and bubble volume, is revealed. It is suggested that the variation of surface tensions and the resultant force balance at the triple line might be responsible for the modified dynamics of the triple line. PMID- 20591395 TI - Choroidal thickness in normal eyes measured using Cirrus HD optical coherence tomography. AB - PURPOSE: To examine choroidal thickness and area in healthy eyes using spectral domain optical coherence tomography (SD-OCT). DESIGN: Retrospective, observational case series. METHODS: Thirty-four eyes (34 subjects), with no retinal or choroidal disease, underwent high-definition raster scanning using SD OCT with frame enhancement software. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microm intervals up to 2500 microm temporal and nasal to the fovea. The central 1-mm area of the choroid was also measured, along with foveal thickness of the retina. All measurements were performed by 2 independent observers. Statistical analysis was used to correlate inter-observer findings, choroidal thickness and area measurements with age, and choroidal thickness with retinal foveal thickness. RESULTS: The 34 subjects had a mean age of 51.1 years. Reliable measurements of choroidal thickness were obtainable in 74% of eyes examined. Choroidal thickness and area measurements had strong inter-observer correlation (r = 0.92, P < .0001 and r = 0.93, P < .0001 respectively). Area had a moderate negative correlation with age (r = -0.62, P < .0001) that was comparable to the correlation between mean subfoveal choroidal thickness and age (r = -0.61, P < .0001). Retinal and choroidal thickness were found to be poorly correlated (r = 0.23, P = .18). Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and then thinning again temporally. Mean subfoveal choroidal thickness was found to be 272 microm (SD, +/- 81 microm). CONCLUSIONS: Choroidal thickness can be measured using SD-OCT high definition raster scans in the majority of eyes. Choroidal thickness across the macula demonstrates a thin choroid nasally, thickest subfoveally, and again thinner temporally, and a trend toward decreasing choroidal thickness with age. PMID- 20591396 TI - Use of intraoperative fourier-domain anterior segment optical coherence tomography during descemet stripping endothelial keratoplasty. AB - PURPOSE: To evaluate the intraoperative use of handheld Fourier-domain optical coherence tomography (OCT) during Descemet stripping automated endothelial keratoplasty (DSAEK) to assess the donor-host interface. DESIGN: Prospective, observational case series. METHODS: Six patients undergoing DSAEK surgery were included. OCT scans of the cornea were performed intraoperatively after insertion of the donor disc, after instillation of air in the anterior chamber beneath the disc, after vent incisions in the host cornea in each quadrant, following air fluid exchange at the end of operation, and on day 1 after surgery. The central 3 mm of each cornea was scanned. The broadest gap between donor and host cornea (interface space) was measured. RESULTS: Adequate readings could be obtained from all patients without any complications. In 2 patients there was a decrease in the width of the interface space after each surgical step documented by the OCT scans. At the end of their operation, no interface space was detectable. In 2 patients, interface space disappeared after the vent incisions and did not reappear during the further course of the surgery. In further 2 patients the separation between the host and donor was still detectable at the end of the operation. All patients had no detectable interface gap on day 1. CONCLUSIONS: Handheld anterior segment OCT can be used to assess the host-donor interface in lamellar corneal transplantation surgery. Donor adherence can occur in spite of residual interface space at the end of surgery. Further studies should be conducted to answer the question of which surgical steps are useful in assisting with donor adhesion. PMID- 20591397 TI - Inhibition of corneal neovascularization by topical bevacizumab (Anti-VEGF) and Sunitinib (Anti-VEGF and Anti-PDGF) in an animal model. AB - PURPOSE: To evaluate the effects of topically applied bevacizumab and sunitinib on experimentally induced corneal neovascularization. DESIGN: Experimental animal study. METHODS: Thirty-six New Zealand rabbits were involved. One eye per rabbit was used. Corneal neovascularization was induced by placing 5 silk sutures in the upper cornea. Rabbits were randomized to 1 of 3 groups (12 rabbits each): Group 1 received saline 0.9%, Group 2 bevacizumab 5 mg/mL, and Group 3 sunitinib 0.5 mg/mL. All treatments were administered 3 times daily for 14 days. Photographs were taken on a slit lamp on days 7 and 14, and angiographic photographs were taken on day 14. The area of neovascularization was measured in mm(2), percentage of the total corneal area, and percentage of the corneal surface covered by sutures. RESULTS: On day 14, corneal neovascularization area in Group 1 (25.92 +/ 5.08 mm(2), 18.78% +/- 3.5% of corneal surface, 105.59% +/- 18.9% of corneal surface with sutures) was larger than in Groups 2 (18.52 +/- 7.94 mm(2), 13.67% +/- 5.8%, 76.35% +/- 33.2%) (1-way analysis of variance, P = .041) and 3 (4.57 +/ 2.32 mm(2), 3.40% +/- 1.7%, 18.94% +/- 9.2%)(P < .001). Neovascularization in Group 2 was larger than in Group 3 (P < .001). Compared to saline, corneal neovascularization was inhibited 28.5% by bevacizumab and 82.3% by sunitinib. Sunitinib settled on the iris. CONCLUSIONS: Topical administration of both bevacizumab and sunitinib inhibits corneal neovascularization in rabbits. But vascular endothelial growth factor (VEGF) pathway blockade by bevacizumab was not sufficient for a profound inhibition. Blocking both VEGF and platelet-derived growth factor pathways using sunitinib was 3-fold more effective. PMID- 20591398 TI - One-year outcomes after retinal detachment surgery among medicare beneficiaries. AB - PURPOSE: To determine longitudinal rates of second retinal detachment operation and postoperative adverse outcomes after retinal detachment surgery in a nationally representative sample of older Americans. DESIGN: Retrospective, longitudinal cohort analysis. METHODS: A total of 9216 Medicare beneficiaries were identified from the Medicare 5% sample who were diagnosed with rhegmatogenous retinal detachment and underwent primary pars plana vitrectomy (PPV), scleral buckle, pneumatic retinopexy, or laser photocoagulation or cryotherapy alone. Rhegmatogenous retinal detachment, PPV, scleral buckle, pneumatic retinopexy, or laser photocoagulation/cryotherapy was ascertained from International Classification of Diseases and Current Procedural Terminology procedure codes. Rates of second retinal detachment operation and postoperative adverse outcomes were analyzed by cumulative incidence and logistic regression to control for prior adverse outcome measures and demographic factors. RESULTS: At 1 year follow-up, the rate of receipt of a second retinal detachment operation for beneficiaries who had undergone primary pneumatic retinopexy was much higher (40.6%, P < .0001) relative to the scleral buckle (19.2%) group. After controlling for demographic variables and ocular comorbidities, pneumatic retinopexy individuals were nearly 3 times more likely to receive a second retinal detachment surgery than scleral buckle individuals. No significant differences exist in risk of second retinal detachment surgery for the PPV compared to the scleral buckle group. Individuals receiving PPV were 2 times more likely to suffer adverse outcomes than were those undergoing scleral buckle. Results were robust in sensitivity analysis. CONCLUSIONS: Rates of second operation were much higher after pneumatic retinopexy than PPV or scleral buckle, and rates of adverse outcomes were higher in PPV, even after controlling for risk factors and demographic variables. PMID- 20591399 TI - Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion: results from the sham-controlled ROCC study. AB - PURPOSE: The ROCC study (randomized study comparing ranibizumab to sham in patients with macular edema secondary to central Retinal vein OCClusion [CRVO]) evaluated the short-term effect of intravitreal ranibizumab injections on best corrected visual acuity (BCVA) and macular edema. DESIGN: Prospective, multicenter, randomized, double-masked, placebo-controlled trial. METHODS: In this 6-month trial, 32 patients with macular edema secondary to CRVO were randomized to receive monthly intravitreal ranibizumab (0.5 mg/0.05 mL) or sham injections for 3 consecutive months. If macular edema persisted, patients received further monthly injections. Primary outcome measures were BCVA and central macular thickness (CMT) at 6 months. RESULTS: Twenty-nine patients completed the study. After 3 months, BCVA improved by a mean +/- standard deviation (SD) of 16 +/- 14 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the ranibizumab group (n = 15), compared with a mean loss of 5 +/- 15 ETDRS letters in the sham group (n = 14; P = .001). The mean +/- SD change in CMT was -411 +/- 200 microm in the ranibizumab group and -86 +/- 165 microm with sham (P < .001). At 6 months, the mean +/- SD change in BCVA was 12 +/- 20 ETDRS letters in the ranibizumab group compared with -1 +/- 17 ETDRS letters in the sham group (P = .067). The mean +/- SD change in CMT was -304 +/- 194 microm with ranibizumab and -151 +/- 205 microm with sham (P = .05). Twelve patients (80%) in the ranibizumab group required more than 3 initial injections; mean +/- SD number of injections was 4.3 +/- 0.9 during the study. CONCLUSION: Monthly ranibizumab significantly increased BCVA and decreased macular edema, compared with sham, in patients with CRVO. Repeated consecutive injections are necessary to maintain initial positive results. PMID- 20591400 TI - Development of a simple model for predicting need for surgery in patients who initially undergo conservative management for adhesive small bowel obstruction. AB - BACKGROUND: Among patients with adhesive small bowel obstruction (ASBO) initially managed with a conservative strategy, predicting risk of operation is difficult. METHODS: We investigated ASBO patients at 2 different periods to derive and validate a clinical prediction model for risk of operation. RESULTS: One hundred fifty-four patients were enrolled into the derivation cohort and 96 into the validation cohort. Based on the derived scoring, including age > or =65 years, presence of ascites, and gastrointestinal drainage volume >500 mL on day 3, each patient was classified into 1 of 4 risk classes from low risk to high risk. When applied to the validation cohort, the positive predictive value (PPV) for operation in the high-risk class was 72%, while the negative predictive value (NPV) in the low-risk class was 100% with high sensitivity (100%) and specificity (96%). CONCLUSIONS: The prediction model performs well for risk stratification of need for surgical intervention following conservative strategy among ASBO patients. PMID- 20591401 TI - Biological scaffolds in reparative surgery for abdominal wall hernias. PMID- 20591402 TI - Commentary for An evidence-based medicine review of lymphadenectomy extent for gastric cancer. PMID- 20591403 TI - Re: A historic perspective on the contributions of surgeons to the understanding of acute pancreatitis. PMID- 20591404 TI - Re: How to avoid unnecessary laparotomies in iatrogenic bile duct injuries? PMID- 20591405 TI - Requirement and postoperative outcomes of abdominal panniculectomy alone or in combination with other procedures in a bariatric surgery unit. AB - BACKGROUND: A high percentage of patients present with redundant skin folds after bariatric surgery. This study aims to quantify the need for panniculectomy after open bariatric surgery and to analyze the postoperative outcomes. METHODS: A retrospective cohort study was performed. The patients were divided into 2 groups: group DLP, patients who underwent an abdominal panniculectomy alone and group DLP+, those who underwent panniculectomy in association with another surgical procedure. RESULTS: Four hundred forty-six patients underwent open bariatric surgery and 130 patients (29%) subsequently required an abdominal dermolipectomy. Seventy-six percent presented also incisional hernia and 8% presented cholelithiasis. Forty-six percent of patients presented postoperative complications: wound seroma/infection (21%), wound dehiscence due to skin necrosis (13%), and hemorrhage/hematoma (10%) were the most frequent. There were no major complications or mortality. DLP+ was not associated with an increase in complications. CONCLUSIONS: After open bariatric surgery, an abdominal panniculectomy is often required. This procedure has a high postoperative morbidity in these patients, although complications are usually mild. There is not an increase in the rate of complications when panniculectomy is associated with other procedures. PMID- 20591406 TI - The omentum is a site of stromal cell-derived factor 1alpha production and reservoir for CXC chemokine receptor 4-positive cell recruitment. AB - BACKGROUND: The mechanism of the omental response to injury remains poorly defined. This study investigates the omental reaction to a foreign body, examining the role of a chemokine ligand/receptor pair known to play a crucial role in angiogenesis and wound healing. METHODS: A ventral hernia, surgically created in the abdominal wall of 6 swine, was repaired with silicone sheeting to activate the omentum. Omental thickness was determined by ultrasonography. Serial stromal cell-derived factor 1alpha (SDF-1alpha) concentrations were measured in blood, wound, and peritoneal fluids by enzyme-linked immunosorbent assay. RESULTS: During the 14-day study period, serial ultrasonography showed a 20-fold increase in omental thickness, and enzyme-linked immunosorbent assay revealed a 4 fold increase in SDF-1alpha concentration in local wound fluid. Omental vessel count and vascular surface area were 8- to 10-fold higher in reactive omentum. Immunohistochemistry showed nearly complete replacement of control omental fat with CXC chemokine receptor 4 (CXCR4)-positive cells by day 14. CONCLUSIONS: Activated omentum, important in the SDF-1alpha/CXCR4 axis, may serve as an intraperitoneal reservoir for recruitment of circulating bone marrow-derived cells vital to healing. PMID- 20591407 TI - A vanishing species. PMID- 20591408 TI - Patient attitudes to surgeons' attire in an outpatient clinic setting: substance over style. AB - BACKGROUND: It is believed that patients prefer that surgeons convey a professional appearance with traditional business attire and white laboratory coat. We performed a prospective study to assess patient opinions regarding traditional attire versus the wearing surgical scrubs in the outpatient setting. METHODS: During a 5-month period, surgeons alternated wearing traditional clothing and surgical scrubs. Adult patients were given a questionnaire assessing their preferences regarding surgeons' clothing. RESULTS: Six hundred twelve patients returned the questionnaire. The majority felt that scrubs were appropriate attire for physicians. Half of the patients felt that wearing white laboratory coats is necessary. A minority felt that their surgeon's dress affects their opinion regarding the care they received. There was no difference between responses regardless of the attire actually worn. CONCLUSIONS: Surgeon's clothing choice does not significantly influence patient's opinion of the care they receive. Patients do not have strong preferences for white coats or more traditional surgical attire. PMID- 20591409 TI - The effect of sinusoidal rolling ground motion on lifting biomechanics. AB - The objective of this study was to quantify the effects of ground surface motion on the biomechanical responses of a person performing a lifting task. A boat motion simulator (BMS) was built to provide a sinusoidal ground motion (simultaneous vertical linear translation and a roll angular displacement) that simulates the deck motion on a small fishing boat. Sixteen participants performed lifting, lowering and static holding tasks under conditions of two levels of mass (5 and 10 kg) and five ground moving conditions. Each ground moving condition was specified by its ground angular displacement and instantaneous vertical acceleration: A): +6 degrees , -0.54 m/s(2); B): +3 degrees , -0.27 m/s(2); C): 0 degrees , 0m/s(2); D): -3 degrees , 0.27 m/s(2); and E): -6 degrees , 0.54 m/s(2). As they performed these tasks, trunk kinematics were captured using the lumbar motion monitor and trunk muscle activities were evaluated through surface electromyography. The results showed that peak sagittal plane angular acceleration was significantly higher in Condition A than in Conditions C, D and E (698 degrees /s(2) vs. 612-617 degrees /s(2)) while peak sagittal plane angular deceleration during lowering was significantly higher in moving conditions (conditions A and E) than in the stationary condition C (538-542 degrees /s(2) vs. 487 degrees /s(2)). The EMG results indicate that the boat motions tend to amplify the effects of the slant of the lifting surface and the external oblique musculature plays an important role in stabilizing the torso during these dynamic lifting tasks. PMID- 20591410 TI - Radiographic measurement of the cervical spine in patients with temporomandibular dysfunction. AB - AIM: To compare the craniocervical angles and distances between temporomandibular dysfunction (TMD) and free TMD subjects. CASUISTIC AND METHODS: The sample consisted of young adults, of both genders, with age ranging between 18 and 30 years. TMD diagnosis was based on the clinical criteria of the Research Diagnostic Criteria for TMD (RDC/TMD), associated with self-reported symptoms of TMD. For radiological analysis we measured three angles and two distances of craniocervical region. RESULTS: Of the 56 subjects, only 23 completed all stages of research, which were divided into two groups: (1) free TMD group - composed of 11 individuals; (2) TMD group - constituted of 12 subjects. The most common clinical diagnosis of TMD was arthralgia (75.0%) followed by myofascial pain without limited mouth opening (58.4%). Among the self-reported symptoms of TMD, the most frequents were facial (83.4%) and neck (66.6%) pain. Of radiological measurement, only plane atlas angle (APA) (p=0.026) and anterior translation distance (Tz C(2)-C(7)) (p=0.045) showed statistical difference between groups TMD (APA=16.7+/-1.63; Tz C(2)-C(7)=28.7+/-2.58) and free TMD (APA=21.64+/-1.24; Tz C(2)-C(7)=19.82+/-3.29). CONCLUSION: It could be verified that the symptomatic TMD patients presented a flexion of the first cervical vertebra associated with an anteriorization of the cervical spine (hyperlordosis). PMID- 20591411 TI - The effects of peroxidase on the enzymatic and candidacidal activities of lysozyme. AB - OBJECTIVE: To investigate the effects of peroxidase or the peroxidase system on the enzymatic and candidacidal activities of lysozyme. DESIGN: The effects of peroxidase on lysozyme were examined by incubating hen egg-white lysozyme (HEWL) with bovine lactoperoxidase (bLPO). The influence of the peroxidase system on lysozyme was examined by the subsequent addition of potassium thiocyanate and hydrogen peroxide. Lysozyme activity was determined by the turbidity measurement of a Micrococcus lysodeikticus substrate suspension. Candidacidal activity was determined by comparing the colony forming units of Candida albicans ATCC 10231, ATCC 18804, and ATCC 11006. The Wilcoxon signed rank test was used to analyze the effects of variables. RESULTS: bLPO at physiological concentrations enhanced the enzymatic activity of HEWL and its effect was dependent on bLPO concentration. The enhancement of enzymatic activity of HEWL by bLPO was affected by pH and ionic strength. The addition of potassium thiocyanate and hydrogen peroxide did not lead to an additional enhancement of the enzymatic activity of HEWL, as compared with bLPO alone. HEWL displayed candidacidal activity in all 3 strains of C. ablicans. The addition of bLPO alone did not affect the candidacidal activity of HEWL, but the bLPO system enhanced candidacidal activity of HEWL in all 3 strains of C. ablicans. CONCLUSIONS: bLPO enhanced the enzymatic activity of HEWL, but the bLPO system did not show additional enhancement of the enzymatic activity of HEWL. The addition of bLPO did not affect the candidacidal activity of HEWL, but the bLPO system did enhance the candidacidal activity of HEWL. PMID- 20591412 TI - Cognitive style and depressive symptoms in elderly people - extending the empirical evidence for the cognitive vulnerability-stress hypothesis. AB - INTRODUCTION: Depression is common in older people and its identification and treatment has been highlighted as one of the major challenges in an ageing world. Poor physical and cognitive health, bereavement, and prior depression are important risk factors for depression in elderly people. Attributional or cognitive style has been identified as a risk factor for depression in children, adolescents and younger adults but its relevance for depression and mood in elderly people has not been investigated in the context of other risk factors. METHOD: Sixty-four older adults from an 'extra care' living scheme (aged 59-97) were recruited for a 6-week prospective study to examine the relationships between cognitive style and depressive symptoms. RESULTS: Regression analyses revealed that, when other risk factors were controlled for, cognitive style and its interaction with stress predicted changes in depressive symptoms, therefore partially replicating prior research. CONCLUSION: Cognitive-stress-vulnerability models also apply to elderly populations, but may be rather predictive of changes in depression when facing lower levels of stress. PMID- 20591413 TI - Specificity of cognitive emotion regulation strategies: a transdiagnostic examination. AB - Despite growing interest in the role of regulatory processes in clinical disorders, it is not clear whether certain cognitive emotion regulation strategies play a more central role in psychopathology than others. Similarly, little is known about whether these strategies have effects transdiagnostically. We examined the relationship between four cognitive emotion regulation strategies (rumination, thought suppression, reappraisal, and problem-solving) and symptoms of three psychopathologies (depression, anxiety, and eating disorders) in an undergraduate sample (N=252). Maladaptive strategies (rumination, suppression), compared to adaptive strategies (reappraisal, problem-solving), were more strongly associated with psychopathology and loaded more highly on a latent factor of cognitive emotion regulation. In addition, this latent factor of cognitive emotion regulation was significantly associated with symptoms of all three disorders. Overall, these results suggest that the use of maladaptive strategies might play a more central role in psychopathology than the non-use of adaptive strategies and provide support of a transdiagnostic view of cognitive emotion regulation. PMID- 20591414 TI - Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. AB - BACKGROUND: Circadian rhythm abnormalities are strongly associated with bipolar disorder; however the role of circadian genes in mood regulation is unclear. Previously, we reported that mice with a mutation in the Clock gene (ClockDelta19) display a behavioral profile that is strikingly similar to bipolar patients in the manic state. METHODS: Here, we used RNA interference and viral mediated gene transfer to knock down Clock expression specifically in the ventral tegmental area (VTA) of mice. We then performed a variety of behavioral, molecular, and physiological measures. RESULTS: We found that knockdown of Clock, specifically in the VTA, results in hyperactivity and a reduction in anxiety related behavior, which is similar to the phenotype of the ClockDelta19 mice. However, VTA-specific knockdown also results in a substantial increase in depression-like behavior, creating an overall mixed manic state. Surprisingly, VTA knockdown of Clock also altered circadian period and amplitude, suggesting a role for Clock in the VTA in the regulation of circadian rhythms. Furthermore, VTA dopaminergic neurons expressing the Clock short hairpin RNA have increased activity compared with control neurons, and this knockdown alters the expression of multiple ion channels and dopamine-related genes in the VTA that could be responsible for the physiological and behavioral changes in these mice. CONCLUSIONS: Taken together, these results suggest an important role for Clock in the VTA in the regulation of dopaminergic activity, manic and depressive-like behavior, and circadian rhythms. PMID- 20591415 TI - A role for p11 in the antidepressant action of brain-derived neurotrophic factor. AB - BACKGROUND: The protein p11 (also called S100A10) is downregulated in human and rodent depressive-like states. Considerable experimental evidence also implicates p11 in the mechanism of action of antidepressant drugs and electroconvulsive seizures, in part due to its interaction with specific serotonin receptors. Brain derived neurotrophic factor (BDNF) has been linked to the therapeutic activity of antidepressants in rodent models and humans. In the current study, we investigated whether BDNF regulates p11 in vitro and in vivo. METHODS: We utilized primary neuronal cultures, in vivo analyses of transgenic mice, and behavioral techniques to assess the effects of BDNF on p11. RESULTS: Results indicate that BDNF stimulates p11 expression through tropomyosin-related kinase B (trkB) receptors and via the mitogen-activated protein kinase signaling pathway. Brain-derived neurotrophic factor-induced changes in p11 in vivo correlate with changes in ligand binding to the 5-hydroxytryptamine receptor 1B, the subcellular localization of which is known to be regulated by p11. Behavioral studies demonstrate that p11 knockout mice are insensitive to the antidepressant actions of BDNF. CONCLUSIONS: Taken together, our data demonstrate that p11 levels are regulated by BDNF in vitro and in vivo and that the antidepressant-like effect of BDNF in two well-established behavioral models requires p11. These data support a role for p11 in the antidepressant activity of neurotrophins. PMID- 20591416 TI - Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma. AB - BACKGROUND: Do genetic or epigenetic factors play a role in making some individuals more vulnerable than others to loss of attachment figures or other traumatic experiences? METHODS: DNA was obtained from growth phase entrained Epstein-Barr Virus (EBV) transformed lymphoblast cell lines from 143 adopted participants. Genotype of the serotonin transporter linked polymorphic region (5HTTLPR) was determined, and methylation ratios for each of the C-phosphate-G (CpG) residues were assessed using quantitative mass spectroscopy. Unresolved loss or trauma was established using the Berkeley Adult Attachment Interview. RESULTS: Higher levels of methylation of the 5HTT promoter associated CpG island were associated with increased risk of unresolved responses to loss or other trauma in carriers of the usually protective 5HTTLPR//variant. The ss variant of 5HTTLPR predicted more unresolved loss or trauma, but only in case of lower levels of methylation. Higher levels of methylation of the ss variant were associated with less unresolved loss or other trauma. CONCLUSIONS: Associations between 5HTTLPR polymorphisms and psychological problems are significantly altered by environmentally induced methylation patterns. Methylation may serve as the interface between adverse environment and the developing organism. PMID- 20591417 TI - Attentional bias, emotion recognition, and emotion regulation in anorexia: state or trait? AB - BACKGROUND: Anorexia nervosa (AN) is associated with difficulties in emotion recognition and regulation and with attentional biases to social affective stimuli. This study aimed to examine these factors in a group of women following long-term recovery from AN. METHODS: The Reading the Mind in the Eyes task, Difficulties in Emotion Regulation Scale, and a computerized pictorial Stroop task (angry and neutral faces) were administered to 175 women: 50 with acute AN, 35 recovered from AN, and 90 healthy control subjects (HCs). RESULTS: The recovered group had a significantly higher social and angry-threat attentional bias than HCs, with medium effect sizes, and significantly lower scores on the emotion recognition measure than HCs, with a medium effect size. On the other hand, the recovered group did not significantly differ from the HC group in terms of emotion regulation. CONCLUSIONS: Attentional biases to social affective pictorial stimuli and difficulties with emotion recognition appear to be traits associated with a lifetime history of AN, whereas emotion regulation difficulties appear to remit when the individual successfully recovers from the illness. PMID- 20591418 TI - Molecular mobility studies on the amorphous state of disaccharides. I-thermally stimulated currents and differential scanning calorimetry. AB - The relaxational processes in amorphous solid gentiobiose and cellobiose are studied by thermally stimulated depolarization currents (TSDC) in the temperature region from 108K up to 423K. The slow molecular mobility was characterized in the crystal and in the glassy state. The features of different motional components of the secondary relaxation have been monitored as a function of time as the glass structurally relaxes on aging. It is concluded that some modes of motion of this mobility are aging independent, while others are affected by aging. The value of the steepness index or fragility (T(g)-normalized temperature dependence of the relaxation time) was obtained by differential scanning calorimetry (DSC) from the analysis of the scanning rate dependency of T(g). PMID- 20591419 TI - Morphology and antibacterial activity of carbohydrate-stabilized silver nanoparticles. AB - Silver nanoparticles were prepared by a simple hydrothermal route and chemical reduction using carbohydrates (sucrose, soluble and waxy corn starch) as reducing as well as stabilizing agents. The crystallite size of these nanoparticles was evaluated from X-ray diffraction (XRD) and transmission electron microscopy (TEM) and was found to be 25nm. The effect of carbohydrates on the morphology of the silver nanocomposites was studied using scanning EM (SEM). The nanocomposites exhibited interesting inhibitory as well as bactericidal activity against both Gram positive and Gram negative bacteria. Incorporation of silver also increased the thermal stability of the carbohydrates. PMID- 20591420 TI - A highly alpha-selective glycosylation for the convenient synthesis of repeating alpha-(1-->4)-linked N-acetyl-galactosamine units. AB - The repeating GalpNAc-alpha-(1-->4)-GalpNAc unit is part of a series of essential structures that can be found in many important biomolecules such as the glycoproteins and the O-antigenic polysaccharides of clinically important bacterial strains. In this paper, we describe an exclusive alpha-selective glycosylation reaction, using a 4,6-di-O-tert-butyldimethylsilyl-N acetyloxazolidinone-protected thioglycoside as the glycosyl donor, under pre activation conditions, with only half amount of the promoter, providing the product GalpNAc-alpha-(1-->4)-GalpNAc in high isolated yield. This reaction can be also applied to increasing the length of the repeating structure, which is of significant use in further synthesis of branched or linear oligosaccharides. PMID- 20591421 TI - Synthesis and biological activity of ester and ether analogues of alpha galactosylceramide (KRN7000). AB - Alpha-Galactosylceramide (alphaGalCer, KRN7000) has been identified as a modulator of immunological processes through its capacity to bind iNKT cells mediated by CD1d molecules. Some analogues in while the amide group in alphaGalCer is replaced with ester or ether groups were synthesized from d arabinitol or l-ribose to evaluate their ability to activate iNKT cells. Ester analogues 30a, 31a, and 61 showed activity for IFNgamma and IL-4 production of iNKT cells, while ether (31b) and 4-methoxy ester (76) analogues of alpha galactosylceramide were not active for iNKT cells. PMID- 20591422 TI - Reference frames during the acquisition and development of spatial memories. AB - Four experiments investigated the role of reference frames during the acquisition and development of spatial knowledge, when learning occurs incrementally across views. In two experiments, participants learned overlapping spatial layouts. Layout 1 was first studied in isolation, and Layout 2 was later studied in the presence of Layout 1. The Layout 1 learning view was manipulated, whereas the Layout 2 view was held constant. Manipulation of the Layout 1 view influenced the reference frame used to organize Layout 2, indicating that reference frames established during early environmental exposure provided a framework for organizing locations learned later. Further experiments demonstrated that reference frames established after learning served to reorganize an existing spatial memory. These results indicate that existing reference frames can structure the acquisition of new spatial memories and that new reference frames can reorganize existing spatial memories. PMID- 20591423 TI - Study on the oxidation form of adenine in phosphate buffer solution. AB - The oxidation of adenine in phosphate buffer solution is investigated using square-wave voltammetry and in situ UV spectroelectrochemistry. The geometry of adenine and the derivatives optimized at DFTB3LYP-6-31G (d, p)-PCM level is in agreement with the crystal structure, and the imitated UV spectra of adenine and the product at electrode are consistent with the in situ UV spectra. The relationship between the electrochemical property and the molecular structure is also discussed. The experimental and theoretical results show that the adenine oxidation origins from the neutral adenine. PMID- 20591424 TI - Decision forest for classification of gene expression data. AB - This study attempts to propose an improved decision forest (IDF) with an integrated graphical user interface. Based on four gene expression data sets, the IDF not only outperforms the original decision forest, but also is superior or comparable to other state-of-the-art machine learning methods, especially in dealing with high dimensional data. With an integrated built-in feature selection (FS) mechanism and fewer parameters to tune, it can be trained more efficiently than methods such as support vector machine, and can be built with much fewer trees than other popular tree-based ensemble methods. Moreover, it suffers less from the curse of dimensionality. PMID- 20591425 TI - A hybrid diagnosis model for determining the types of the liver disease. AB - The symptoms of liver diseases are not apparent in the initial stage, and the condition is usually quite serious when the symptoms are obvious enough. Most studies on liver disease diagnosis focus mainly on identifying the presence of liver disease in a patient. Not many diagnosis models have been developed to move beyond the detection of liver disease. The study accordingly aims to construct an intelligent liver diagnosis model which integrates artificial neural networks, analytic hierarchy process, and case-based reasoning methods to examine if patients suffer from liver disease and to determine the types of the liver disease. PMID- 20591426 TI - [International consensus on recommendations for the treatment of patients with upper digestive hemorrhage not associated with esophageal varices]. PMID- 20591427 TI - [Nocardia infection in heart transplant recipients]. AB - INTRODUCTION: The incidence of Nocardia infection in transplant patients ranges between 0.7 and 3% with a high mortality (26-63%). This fact, together with a median time to diagnosis in about two weeks ago that the state of alertness is of vital clinical importance. METHODS: From a cohort of 570 cardiac transplant patients, we reviewed the medical records of those who underwent the diagnosis of Nocardia infection during follow-up. RESULTS: We identified four cases (incidence 0.73%), two scattered. In all, had pulmonary involvement. Mortality was high (2 of 4 patients). CONCLUSION: In cardiac transplant patients Nocardia infection is rare but has a high mortality, being necessary an early diagnosis to establish an appropriate treatment. PMID- 20591428 TI - The human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg2+) and organic mercury (CH3Hg+): mechanism and kinetics. AB - Human arylamine N-acetyltransferase 1 (NAT1) is a xenobiotic-metabolizing enzyme that biotransforms aromatic amine chemicals. We show here that biologically relevant concentrations of inorganic (Hg2+) and organic (CH3Hg+) mercury inhibit the biotransformation functions of NAT1. Both compounds react irreversibly with the active-site cysteine of NAT1 (half-maximal inhibitory concentration (IC50)=250 nM and kinact=1.4x10(4) M(-1) s(-1) for Hg2+ and IC50=1.4 microM and kinact=2x10(2) M(-1) s(-1) for CH3Hg+). Exposure of lung epithelial cells led to the inhibition of cellular NAT1 (IC50=3 and 20 microM for Hg2+ and CH3Hg+, respectively). Our data suggest that exposure to mercury may affect the biotransformation of aromatic amines by NAT1. PMID- 20591429 TI - S100 proteins interact with the N-terminal domain of MDM2. AB - S100 proteins interact with the transactivation domain and the C-terminus of p53. Further, S100B has been shown to interact with MDM2, a central negative regulator of p53. Here, we show that S100B bound directly to the folded N-terminal domain of MDM2 (residues 2-125) by size exclusion chromatography and surface plasmon resonance experiments. This interaction with MDM2 (2-125) is a general feature of S100 proteins; S100A1, S100A2, S100A4 and S100A6 also interact with MDM2 (2-125). These interactions with S100 proteins do not result in a ternary complex with MDM2 (2-125) and p53. Instead, we observe the ability of a subset of S100 proteins to disrupt the extent of MDM2-mediated p53 ubiquitylation in vitro. PMID- 20591431 TI - Glucocorticoids, prenatal stress and the programming of disease. AB - An adverse foetal environment is associated with increased risk of cardiovascular, metabolic, neuroendocrine and psychological disorders in adulthood. Exposure to stress and its glucocorticoid hormone mediators may underpin this association. In humans and in animal models, prenatal stress, excess exogenous glucocorticoids or inhibition of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2; the placental barrier to maternal glucocorticoids) reduces birth weight and causes hyperglycemia, hypertension, increased HPA axis reactivity, and increased anxiety-related behaviour. Molecular mechanisms that underlie the 'developmental programming' effects of excess glucocorticoids/prenatal stress include epigenetic changes in target gene promoters. In the case of the intracellular glucocorticoid receptor (GR), this alters tissue-specific GR expression levels, which has persistent and profound effects on glucocorticoid signalling in certain tissues (e.g. brain, liver, and adipose). Crucially, changes in gene expression persist long after the initial challenge, predisposing the individual to disease in later life. Intriguingly, the effects of a challenged pregnancy appear to be transmitted possibly to one or two subsequent generations, suggesting that these epigenetic effects persist. PMID- 20591430 TI - Quality of colonoscopy reporting in community practice. AB - BACKGROUND: Quality endoscopy reporting is essential when community endoscopists perform colonoscopies for veterans who cannot be scheduled at a Veterans Administration (VA) facility. OBJECTIVE: To examine the quality of colonoscopy reports received from community practices and to determine factors associated with more complete reporting, by using national documentation guidelines. DESIGN: Cross-sectional analysis. SETTING: Reports submitted to the Durham VA Medical Center, Durham, North Carolina, from 2007 to 2008. PATIENTS: Subjects who underwent fee-basis colonoscopy. MAIN OUTCOME MEASUREMENTS: Scores created by comparing community reports with published documentation guidelines. Three scores were created, one for each category of information: Universal Elements (found on all endoscopy reports), Indication Elements (specific to the procedure indication), and Finding Elements (specific to examination findings). RESULTS: For the 135 included reports, the summary scores were Universal Elements, 57.6% (95% confidence interval [CI], 55%-60%); Indication Elements, 73.7% (95% CI, 69% 78%); and Finding Elements, 75.8% (95% CI, 73%-79%). Examples of poor reporting included patient history (20.7%), last colonoscopy date (18.0%), average versus high risk screening (32.0%), withdrawal time (5.9%), and cecal landmark photographs (45.2%). Only the use of automated reporting software was associated with more thorough reporting. LIMITATIONS: Modest sample size, mostly male participants, frequent pathologic findings, limited geography, and lack of complete reporting by a minority of providers. CONCLUSIONS: The overall completeness of colonoscopy reports was low, possibly reflecting a lack of knowledge of reporting guidelines or a lack of agreement regarding important colonoscopy reporting elements. Automated endoscopy software may improve reporting compliance but may not completely standardize reporting quality. PMID- 20591432 TI - TLR4 influences the humoral and cellular immune response during polymicrobial sepsis. AB - As part of the innate immune system, Toll-like receptors (TLRs) react rapidly on a pathogen challenge without prior exposure. Although it is well known that TLR4 is associated with the receptor for lipopolysaccharide (LPS), its role during sepsis has not yet been clearly defined. To study this,polymicrobial sepsis was induced in male C3H/HeN (TLR4 wild type) and C3H/HeJ (TLR4 mutant) mice by caecal ligation and puncture (CLP).A total of 48 h following the surgical procedure, the mice were sacrificed and plasma was collected.Kupffer cells were isolated and ex vivo cytokine production and plasma levels were determined. Lung neutrophil influx was investigated by myeloperoxidase (MPO) content and immunohistochemistry. T-cell subtypes in blood and spleen were determined by flow cytometry.Mice with intact TLR4 (wild type) had increased Kupffer cell IL-6 production and increased plasma levels as compared with C3H/HeJ mice following sepsis. Furthermore, wild type mice showed increased neutrophil influx in lungs and lower percentages of CD8+ splenocytes. This was accompanied with less activity, increased weight loss and decreased core temperature.We conclude that TLR4 influences the humoral and cellular response during the course of sepsis and lack of TLR4 reduces markers of the systemic inflammatory response as well as distant organ damage.Therefore, TLR4 could act as a future therapeutic target modulating the immune response during sepsis. PMID- 20591433 TI - Internal kinetic changes in the knee due to high tibial osteotomy are well correlated with change in external adduction moment: an osteoarthritic knee model. AB - In-vivo quantification of loads in the constitutive structures of the osteoarthritic knee can provide clinical insight, particularly when planning a surgery like the opening-wedge high tibial osteotomy (HTO). A computational knee model was created to estimate internal kinetics during walking gait. An optimization approach partitioned loads between the muscles, ligaments, medial and lateral contact surfaces of the tibial-femoral joint. Three kinetic measures were examined in 30 HTO patients: external knee adduction moment (EKAM), medial compartment load (ML) and the medial-to-lateral compartment loads ratio (MLR). Three time points were compared: immediately pre-HTO, 6 and 12 months post-HTO. Three hypotheses were tested: (1) HTO reduces an EKAM, an ML and an MLR, (2) these measures are not significantly different at 6 and 12 months post-HTO, and (3) the change in the impulse of EKAM due to a HTO is well-correlated with the impulse of an MLR. The three hypotheses were confirmed. First peak of an EKAM during stance phase was reduced significantly by 1.70% BW-ht. ML and MLR at the same instance were reduced significantly by 0.56%BW and 1.0, respectively. These measures were not significantly different between 6 and 12 months post-HTO. Changes in impulse of an EKAM and an MLR were moderately well-correlated between the pre-HTO and 6 months post-HTO time points (R(2)=0.5485). Therefore, the external measure EKAM-impulse is a good proxy of the internal kinetic measure of an MLR-impulse, explaining about 55% of the variance in the change due to a HTO intervention. PMID- 20591434 TI - Preconcentration sensitive determination of pyrethroid insecticides in environmental water samples with solid phase extraction with SiO2 microspheres cartridge prior to high performance liquid chromatography. AB - Present study developed a new method for the sensitive determination of pyrethroid insecticides with solid phase extraction in combination with high performance liquid chromatography and UV detector. SiO(2) microspheres, a new SiO(2) based material, was investigated for the enrichment ability and applicability as the solid phase extraction sorbent. Four pyrethroid pesticides such as fenpropathrin, cyhalothrin, fenvalevate and biphenthrin were used as the target analytes. Parameters that maybe influence the extraction efficiency such as the eluent type and its volume, sample flow rate, sample pH, and the sample volume were optimized in detail, and the optimal conditions were as followed: sample volume, 100mL; concentration of methanol, 30%; acetone volume, 5mL; sample flow rate, 4.2mLmin(-1); sample pH, 7. The experimental results indicated that there was good linearity in the concentration range of 0.1-50microgL(-1) except biphenthrin in the range of 0.05-25microgL(-1). The detection limits for fenpropathrin, cyhalothrin, fenvalevate and biphenthrin were in the range of 0.02 0.08microgL(-1). The intra-day and day to day precisions (RSDs, n=6) were in the ranges of 2.6-4.4% and 5.3-7.2%, respectively. The method was validated with five real environmental water samples, and all these results proved that proposed method could be used as a good alternative for the routine analysis for such pollutants in environmental samples. PMID- 20591435 TI - Mass spectrometry assay as an alternative to the enzyme-linked immunosorbent assay test for biomarker quantitation in ecotoxicology: application to vitellogenin in Crustacea (Gammarus fossarum). AB - Vitellogenin (Vg) is a widespread biomarker for measuring exposure to endocrine disruptors. Vg quantification is usually done by using the ELISA test (enzyme linked immunosorbent assay). Since this test is specific to a target protein, it can rarely be used with other species due to low cross-reactivity across species. Therefore alternative analytical methods have to be considered as the development of a specific and sensitive ELISA test for each new target is time-consuming and may prove unsuccessful. This paper focuses on the development of a quantitative assay by liquid chromatography tandem mass spectrometry (LC-MS/MS) of vitelogenin in an invertebrate (Gammarus fossarum) for which no ELISA kit is available. The linearity of the method was within the concentration range 2.5-25,000pg/mL and the limit of detection was estimated at 0.75pg/mL of Vg. This method has been demonstrated to be an alternative to existing immunological methods for quantifying Vg in invertebrates due to its greater sensitivity, specificity and reproducibility (intra- and inter-assay below 15%). This assay was applied for Vg determination in female G. fossarum following exposure to a known endocrine disruptor, methyl farnesoate, in crustaceans. The availability of a quantitative G. fossarum LC-MS/MS assay should open the way for further studies to evaluate xenoestrogen effects in aquatic male G. fossarum. PMID- 20591436 TI - Spermine-graft-dextran non-covalent copolymer as coating material in separation of basic proteins and neurotransmitters by capillary electrophoresis. AB - Spermine-graft-dextran (Spe-g-Dex) copolymer was synthesized and used as a non covalent coating for the separation of proteins and neurotransmitters by capillary electrophoresis. The coating was obtained via flushing the capillary with 1.0% Spe-g-Dex copolymer solution for 2min. Electroosmotic flow (EOF) was strongly suppressed, ranging from -1.60x10(-9) to 3.65x10(-9)m(2)V(-1)s(-1). Effect of experimental conditions, such as the copolymer concentration, the concentration and pH of the background electrolyte (BGE), on the Spe-g-Dex coating was investigated. Separation of lysozyme, cytochrome c, ribonuclease A and alpha-chymotrypsinogen yielded high separation efficiencies ranging from 141000 to 303000plates/m and recoveries from 85.4% to 98.3% at pH 4.0 (284.0mM sodium acetate-acetic acid buffer, I=50mM). Run-to-run repeatabilities and day-to day, and capillary-to-capillary reproducibilities were all below 1.7%. In addition, Spe-g-Dex coating allowed the successful separation of five neurotransmitters, 5-hydroxytryptamine, dopamine, epinephrine, isoprenaline, dobuamine at pH 4.0 with high separation efficiencies of 290000-449000plates/m. PMID- 20591437 TI - Kinetic electro membrane extraction under stagnant conditions--fast isolation of drugs from untreated human plasma. AB - Amitriptyline, citalopram, fluoxetine, and fluvoxamine were isolated by electro membrane extraction (EME) from 70microl of untreated plasma (pH 7.4), through a supported liquid membrane (SLM) of 1-ethyl-2-nitrobenzene immobilized in the pores of a porous polypropylene hollow fiber, and into 30microl of 10mM HCOOH as acceptor solution inside the lumen of the hollow fiber. The driving force of the extraction was a 9V potential sustained over the SLM with a common battery, with the positive electrode placed in the plasma sample and the negative electrode placed in the acceptor solution. Extractions were performed under totally stagnant conditions with a very simple device for 1min (kinetic regime), and subsequently the acceptor solution was analyzed directly by liquid chromatography mass spectrometry (LC-MS). Recoveries were 12, 13, 22, and 17% for fluoxetine, amitriptyline, citalopram, and fluvoxamine, respectively. Sample clean-up was comparable to reversed-phase solid-phase extraction (SPE), but EME required substantially less time than SPE. The time advantage of EME was further improved by parallel extraction of three samples (for 1min) with the same 9V battery. EME from plasma combined with LC-MS provided limits of quantification (S/N=10) in the range 0.4-2.3ng/ml, linearity in the range 1-1000ng/ml with r(2)-values of 0.998 0.999, and repeatability in the range 3.2-8.9% RSD in the mid-therapeutic window (100ng/ml). PMID- 20591438 TI - Trace analysis of isothiazolinones in water samples by large-volume direct injection liquid chromatography tandem mass spectrometry. AB - Isothiazolinones are used as preservatives, biocides and disinfectants in a variety of industrial and domestic applications. Some of the isothiazolinones are difficult to isolate from water due their high polarity. A sensitive and selective analytical method was developed and optimized for the determination of sub-microg/L levels of three isothiazolinones in water samples. Three isothiazolinones are described in this paper: 2-methyl-3-isothiazolinone, 5 chloro-2-methyl-3-isothiazolinone and 4,5-dichloro-2-methyl-3-isothiazolinone. The analytical method involves a robust large-volume direct on-column loop injection of 2 mL on an Aqua ODS HPLC column and tandem MS detection (HPLC MS/MS). After filtration, samples are directly injected without further pretreatment. Detection limits of the individual target compounds were between 0.03 and 0.1 microg/L employing Multi-Reaction Monitoring (MRM) mass spectrometry. Based on the constant ratio of two selected product-ions together with the retention time, the identification is very selective and quantification is reliable. The method was successfully applied to real samples of membrane flushings, drinking water, surface waters and waste water. Additional investigations showed the instability of the isothiazolinones in river- and waste water. Preservation of river water and waste water samples with sodium azide (NaN(3)) promotes the stability of the isothiazolines in solution. In membrane flushings, waste water, surface waters and drinking water, levels of the three isothiazolinones were all below the limit of detection. In effluents of households containing washings from normal shampoo use, isothiazolinones could be detected. PMID- 20591439 TI - Resonance elastic light scattering (RELS) spectroscopy of fast non-Langmuirian ligand-exchange in glutathione-induced gold nanoparticle assembly. AB - The interactions of a biomolecule glutathione (GSH) with citrate-capped gold nanoparticles (AuNP) have been investigated to evaluate the viability of a rapid GSH-capture by gold nanoparticle carriers, as a model system for applications ranging from designing nanoparticle-enhanced functional biosensor interfaces to nanomedicine. The measurements, performed using resonance elastic light scattering (RELS) spectroscopy, have shown a strong dependence of GSH-induced scattering cross-section on gold nanoparticle size. A large increase in RELS intensity after injection of GSH, in a short reaction time (tau=60 s), has been observed for small AuNP (5nm dia.) and ascribed to the fast ligand-exchange followed by AuNP assembly. The unexpected non-Langmuirian concentration dependence of scattering intensity for AuNP (5 nm) indicates on a 2D nucleation and growth mechanism of the ligand-exchange process. The ligand-exchange and small nanoparticle ensemble formation followed by relaxation have been observed in long term (10 h) monitoring of GSH-AuNP interactions by RELS. The results of molecular dynamics and quantum mechanical calculations corroborate the mechanism of the formation of hydrogen-bonded GSH-linkages and interparticle interactions and show that the assembly is driven by multiple H-bonding between GSH-capped AuNP and electrostatic zwitterionic interactions. The RELS spectroscopy has been found as a very sensitive tool for studying interparticle interactions. The application of RELS can be expanded to monitor reactivities and assembly of other monolayer-protected metal clusters, especially in very fast processes which cannot be followed by other techniques. PMID- 20591440 TI - Haemorrhagic diathesis in a ram with Anaplasma phagocytophilum infection. AB - A 10-month-old ram with fever, inappetence and haemorrhagic diathesis had petechiae and ecchymoses at various body sites and was infested by ticks. Haematological examination revealed pancytopenia, while serum biochemistry indicated hepatic dysfunction. Blood smears were negative for Ehrlichia spp. and other haemoparasites. Paired sera revealed infection by Anaplasma phagocytophilum, but testing by polymerase chain reaction was negative. Treatment with oxytetracycline was effective. This is the first reported clinical case of ovine anaplasmosis in Greece caused by A. phagocytophilum. PMID- 20591441 TI - The frequency of electrocardiographic errors due to electrode cable switches: a before and after study. AB - INTRODUCTION: Electrocardiographic (ECG) errors due to electrode cable reversal confuse physicians and provoke unnecessary diagnostic tests. They occur in approximately 4% of ECGs performed in the intensive care unit (ICU). We aimed to investigate whether this frequency could be reduced by an appropriate intervention. METHODS: All ECGs from consecutive patients were collected at ICU discharge and analyzed by the investigators. Before collecting a second set of ECGs, we educated our ICU staff and performed technical improvements on the electrocardiographs (system approach). Electrocardiographic errors were identified applying previously published morphologic criteria. RESULTS: We collected and analyzed 1123 ECGs from 416 patients. Nine hundred ten ECGs (81%) were recorded in the ICU; and the frequencies of electrode cable misplacements before and after the intervention were 4.8% and 1.2%, respectively (P = .002). CONCLUSIONS: Using a system approach, we were able to significantly reduce the frequency of ECG errors due to electrode cable switches by 75%. PMID- 20591443 TI - Splenomegaly as presentation of a wandering spleen. PMID- 20591442 TI - The absence of the ST-segment elevation in acute coronary artery thrombosis: what does not fit, the patient or the explanation? AB - In a few patients with acute proximal thrombotic occlusion of the left anterior descending coronary artery (LAD), tall ischemic T waves never evolve into ST segment elevation. This was recently inaccurately reported as a "novel sign" of proximal LAD occlusion. It has been speculated that the absence of ST-segment elevation could be attributed to the large area of transmural ischemia, the anatomic variant of Purkinje fibers, or to lack of activation of sarcolemal adenosine triphosphate-potassium channels. This electrocardiographic picture was recently explained by changes in the subendocardial but not in the epicardial action potential, suggesting subendocardial ischemia as the underlying mechanism. We present a patient with thrombotic lesion of proximal LAD, static precordial ST segment depression, and tall T waves who underwent primary percutaneous intervention and stent placement. Surprisingly, total thrombotic stent occlusion on the following day was associated with ST-segment elevation in precordial leads, indeed supporting the concept of the regional subendocardial ischemia that was first described more than a decade ago. PMID- 20591444 TI - Complete mapping of the tricuspid valve apparatus using three-dimensional sonomicrometry. AB - OBJECTIVE: Many surgeons consider the tricuspid valve to be a second-class structure. Our objective was to determine the normal anatomy and dynamic characteristics of the tricuspid valve apparatus in vivo and to discern whether this would aid the design of a tricuspid valve annuloplasty ring model. METHODS: Sixteen sonomicrometry crystals were placed around the tricuspid annulus, at the bases and tips of the papillary muscles, the free edges of the leaflets, and the right ventricular apex during cardiopulmonary bypass in 5 anesthetized York Hampshire pigs. Animals were studied after weaning of cardiopulmonary bypass on 10 cardiac cycles of normal hemodynamics. RESULTS: Sonomicrometry array localizations demonstrate the multiplanar shape of the tricuspid annulus. The tricuspid annulus reaches its maximum area (97.9 +/- 25.4 mm(2)) at the end of diastole and its minimum area (77.3 +/- 22.5 mm(2)) at the end of systole, and increases again in early diastole. Papillary muscles shorten by 0.8 to 1.5 mm (11.2%) in systole, and chordae tendineae straighten by 0.8 to 1.7 mm (11.4%) in systole. CONCLUSIONS: The shape of the tricuspid annulus is a multiplanar 3 dimensional one with its highest point at the anteroseptal commissure and its lowest point at the posteroseptal commissure, and the anteroposterior commissure is in a middle plane in between. The tricuspid annulus area reaches its maximum during diastole and its minimum during systole. The papillary muscles contract by the same amount of chordal straightening. The optimal tricuspid annuloplasty ring may be a multiplanar 3-dimensional one that mimics the normal tricuspid annulus. PMID- 20591445 TI - Branched vascular network architecture: a new approach to lung assist device technology. AB - OBJECTIVE: A lung assist device would serve an important clinical need as a bridge to transplant or destination therapy for patients with end-stage lung disease. A new lung assist device has been developed that incorporates a branched network of vascular channels adjacent to a gas chamber, separated by a thin, gas permeable membrane. This study investigated 2 potential gas exchange membranes within this new architecture. METHODS: Oxygen and carbon dioxide exchange within the device was tested in vitro using 3 gas-permeable membranes. Two of the membranes, silicone only and silicone-coated microporous polymer, were plasma impermeable. The third, a microporous polymer, was used as a control. Gas exchange testing was done using anticoagulated porcine blood over a range of flow rates. RESULTS: Oxygen and carbon dioxide transfer was demonstrated in the device and increased nearly linearly from 0.6 to 8.0 mL/min blood flow for all of the membranes. There was no significant difference in the gas transfer between the silicone and the silicone-coated microporous polymer membranes. The transfer of oxygen and carbon dioxide in the device was similar to existing hollow fiber oxygenators controlling for surface area. CONCLUSIONS: The silicone and silicone coated microporous polymer membranes both show promise as gas-permeable membranes in a new lung assist device design. Further optimization of the device by improving the membranes and reducing the channel diameter in the vascular network will improve gas transfer. The current device may be scaled up to function as an adult lung assist device. PMID- 20591446 TI - Reconstruction of a resected subclavian vein by transposition of the ipsilateral internal jugular vein. PMID- 20591447 TI - Bioaccumulation from food and water of cadmium, selenium and zinc in an estuarine fish, Ambassis jacksoniensis. AB - The glassfish, Ambassis jacksoniensis, is a key, mid-level species in an estuarine food web on the east coast of Australia. Estuaries are subject to contamination from urban and industrial activities. The biokinetics of Cd, Se and Zn accumulation by glassfish from water and food were assessed using radioisotopes. Metal uptake from water was not regulated over the range of water metal concentrations examined. Metal uptake from food was assessed using brine shrimp (Artemia sp.) fed radio-labelled algae. The assimilation efficiency from food was 9.5 +/- 2.5%, 23 +/- 2.2% and 4.6 +/- 0.6% for Cd, Se and Zn, respectively. The potential for biomagnification was low for all metals. Food is the main metal uptake pathway for glassfish, with 97%, 99% and 98% of the uptake of Cd, Se and Zn, respectively, estimated to be from food. PMID- 20591448 TI - [Free software: an opportunity for researchers]. PMID- 20591449 TI - [From conventional cytogenetics to microarrays. Fifty years of Philadelphia chromosome]. AB - In 1960 Ph-chromosome was found associated with the presence of chronic myelogenous leukemia. In these 50 years an increasing number of cytogenetic abnormalities have been found associated with hematological malignancies. The presence of these abnormalities is not only important for the diagnosis of the patient, but it also contributes to the prognosis of patients with leukemia or lymphoma. For this reason the WHO classification of hematological disease has included these studies for the correct characterization of leukemias and lymphomas. In addition, the use of FISH and micromatrix methodologies have refined the genetic lesions present in these malignancies. The cytogenetic changes observed also provide further information in relation to the therapy. PMID- 20591450 TI - [Low levels of serotonin in serum correlates with severity of fibromyalgia]. AB - OBJECTIVE: Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology, which affects predominantly women. Among the alterations that have been implicated in the pathophysiology of FM, there have been postulated disturbances in serotonin levels and metabolism, and their implication in symptoms. The aim of the present study was to assess the correlation levels between low levels of serotonin and severity of symptoms in FM. PATIENTS AND METHODS: We determined serotonin levels using an ELISA kit in serum from 38 FM patients and 25 healthy individual. Results were correlated with symptoms regarding pain, depression, impact of disease (FIQ) and age. RESULTS: Serotonin levels were decreased by 45% compared to healthy individual. An important correlation was observed between serotonin levels and predetermined parameters of pain, depression, FIQ and age. CONCLUSION: Serotonin levels are correlated with severity of FM. In addition, there is an interesting correlation between serotonin levels and age of patients. PMID- 20591451 TI - Cervical spinal extradural meningioma: Case report. AB - Extradural meningiomas account for approximately 7% of all spinal meningiomas and are most commonly located in the thoracic spine. Although rare, they should be included in the differential diagnosis of an extradural contrast-enhancing mass. Prognosis depends greatly on the extent of surgical resection. If considered safe, complete resection should be attempted to decrease the risk of recurrence. We report a case of spinal epidural meningioma diagnosed in an elderly woman complaining of right cervicobrachial pain of several years duration, associated with diffuse paresthesia and permanent numbness of her right index finger. The surgical removal of the tumor was incomplete because of the deep lateral extension of the lesion. PMID- 20591452 TI - Effects of glycoalkaloids from Solanum plants on cucumber root growth. AB - The phytotoxic effect of four glycoalkaloids and two 6-O-sulfated glycoalkaloid derivatives were evaluated by testing their inhibition of cucumber root growth. The bioassays were performed using both compounds singly and in equimolar mixtures, respectively. Cucumber root growth was reduced by chaconine (C), solanine (S), solamargine (SM) and solasonine (SS) with IC(50) values of 260 (C), 380 (S), 530 (SM), and 610 microM (SS). The inhibitory effect was concentration dependent. 6-O-sulfated chaconine and 6-O-sulfated solamargine had no inhibitory effects, which indicated that the carbohydrate moieties play an important role in inhibiting cucumber root growth. The equimolar mixtures of paired glycoalkaloids, both chaconine/solanine and solamargine/solasonine, produced synergistic effects on inhibition of cucumber root growth. By contrast, mixtures of unpaired glycoalkaloids from different plants had no obviously synergistic effects. The growth inhibited plant roots lacked hairs, which implied that inhibition was perhaps at the level of root hair growth. PMID- 20591453 TI - Electroencephalographic recordings in dogs: Prevention of muscle artifacts and evaluation of two activation techniques in healthy individuals. AB - This study was performed to improve a standard anesthetic protocol for electroencephalography (EEG) in dogs and to evaluate the effect of photic stimulation and hyperventilation on the EEG of healthy dogs. Ten clinically and neurologically normal beagle dogs were anesthetized with propofol given intravenously with average doses of 7.5mg/kg for induction and 0.37mg/kg/min constant rate infusion for maintenance. Rocuronium bromide (0.4mg/kg IV) was used as a peripheral muscle relaxant in order to prevent muscle artifacts. EEGs were recorded digitally using five subdermal needle electrodes. Photic stimulation and hyperventilation were performed to evaluate two activation techniques commonly used in human EEG recording methods. Monopolar and bipolar montages were analyzed visually and quantitatively. The use of rocuronium produced muscle artifact-free EEG recordings during the given recording procedure which indicates that rocuronium is a valuable adjunct to anesthesia during EEG recording. Photic stimulation and hyperventilation did not provoke paroxysmal discharges in the EEG of healthy dogs. Analysis of quantitative EEG data showed that background activity did not differ significantly between periods with and without stimulation. This data are important basic values and will further help to compare the effects of photic stimulation and hyperventilation of healthy dogs and those suffering from epilepsy. PMID- 20591454 TI - Detection and genetic characterization of peste des petits ruminants virus in free-living bharals (Pseudois nayaur) in Tibet, China. AB - Peste des petits ruminants (PPR) is an important viral disease of sheep and goats. The wildlife hosts of PPR, which may play an important role in the epidemiology of this disease, are not well characterized. The research was undertaken to study the infection of PPR virus (PPRV) in free-living bharals (Pseudois nayaur) in Tibet, China. In 2007, PPRV infection was confirmed in two bharals in Rutog County of Tibet based on clinical signs and detection of PPRV RNA in tissue samples. In 2008, PPRV infection was found in one bharal in Ge'gyai County of Tibet by competitive ELISA, reverse transcription-polymerase chain reaction, and sequence analysis of PPRV fusion protein (F) and nucleoprotein (N) gene segments. The PPRV variant identified in infected bharal was closely related to other circulating PPRV variants recently identified in sheep and goats from Tibet. This is the first report of PPRV infection in free-living bharals. PMID- 20591455 TI - Improved sero-monitoring assay for classical swine fever (CSF) using the recombinant E2 protein of a recent Korean isolate. AB - Classical swine fever (CSF) is a highly contagious disease of pigs that causes fever, diarrhea and paralysis, often resulting in death. E2 is the major structural protein of the CSF virus (CSFV) and mediates the entrance of the virus, subsequently inducing a neutralizing immune response. In this study, the E2 gene of a recent Korean isolate of CSF, SW03, was cloned and the DNA sequence was compared to other strains via phylogenetic analysis. With the purified E2 protein, an enzyme-linked immunosorbent assay (ELISA) was developed for the serodiagnosis of CSFV infection. The sensitivity and specificity of the E2-ELISA were 96.1% and 94.8%, respectively. A total of 17 out of 485 field-collected pig sera tested demonstrated conflicting results between two ELISA methods, a commercial kit and the E2-ELISA. Of these sera, 60% were determined to be CSFV positive by a virus neutralization test (VNT), suggesting involvement of different immune responses in the cases of CSFV infection. As the E2-ELISA was developed using a recent Korean isolate, SW03, this assay is capable of rapidly identifying newly emerging CSFV strains. PMID- 20591456 TI - Expression of rabbits BAFF in Escherichia coli with costimulatory effect on B cell proliferation. AB - In this paper, the cDNA encoding the extracellular soluble domain of rabbit BAFF (rsBAFF) was subcloned into the pET28a vector and the recombinant rsBAFF protein was solubly produced in Escherichia coli. Recombinant rsBAFF protein of 17.1kDa was then purified to a purity of 95% by using Ni(2+)-IDA resin. In vitro, purified rsBAFF protein was able to promote the survival/proliferation of B lymphocytes of rabbits, mice and humans in the presence of anti-IgM antibodies. These findings indicate that the recombinant rsBAFF produced in E. coli have the bioactivity, and functional cross-reactivity occurs between rabbit and other mammalians BAFF proteins. PMID- 20591457 TI - Comparison of the effects of oral hydration and intravenous fluid replacement in adult patients with non-shock dengue hemorrhagic fever in Taiwan. AB - The level of plasma leakage is mild to moderate in patients with non-shock dengue hemorrhagic fever (DHF grade I and grade II), and the necessity of intravenous fluid replacement for these patients remains controversial. We conducted an observational study in adult patients (>18 years) with non-shock DHF admitted to a medical centre in southern Taiwan comparing the effects of oral hydration [group 1 (n=19); age (mean+/-SD) 54.6+/-15.5 years] and intravenous fluid replacement, with a volume of >40ml/kg/day in the first 72h of hospitalization [group 2 (n=30); age 55.9+/-11.6 years]. No significant difference was found in demographics, clinical manifestations, and mean peak level of hematocrit between the two groups. Patients in group 2 had a significantly longer hospital stay compared to those in group 1 (P=0.007), and there was a trend suggesting patients in group 2 were prone to develop pleural effusion and/or pulmonary edema. No difference was found in daily mean pulse pressure, mean hematocrit level, and mean platelet count between the groups for the duration of the 7 days in hospital. All 49 patients survived. Our data suggest that oral hydration may be as effective as intravenous fluid replacement for adults with non-shock DHF and this warrants investigation in a larger series of patients. PMID- 20591458 TI - Origins of the keratometer and its evolving role in ophthalmology. AB - The keratometer, or ophthalmometer as it was originally known, had its origins in the attempt to discover the seat of accommodation in the eye. Since that early beginning, it has been re-invented a number of times, with improvements and modifications made in the original principles of its design for new applications that arose as ophthalmology advanced. The cornea is not only responsible for the majority of the refraction in the eye, but is also readily accessible for measurement and modification. The keratometer's ability to measure the cornea has allowed it to play a central role in critical advances in ophthalmic history. This review describes the origins and principles of this instrument, the novel applications that led to the keratometer's continued resurgences over its nearly 250-year history, and the modern devices that have borrowed its basic principles and are beginning to replace it in common clinical practice. PMID- 20591459 TI - Effects of retroviral envelope-protein cleavage upon trafficking, incorporation, and membrane fusion. AB - Retroviral envelope glycoproteins undergo proteolytic processing by cellular subtilisin-like proprotein convertases at a polybasic amino-acid site in order to produce the two functional subunits, SU and TM. Most previous studies have indicated that envelope-protein cleavage is required for rendering the protein competent for promoting membrane fusion and for virus infectivity. We have investigated the role of proteolytic processing of the Moloney murine leukemia virus envelope-protein through site-directed mutagenesis of the residues near the SU-TM cleavage site and have established that uncleaved glycoprotein is unable either to be incorporated into virus particles efficiently or to induce membrane fusion. Additionally, the results suggest that cleavage of the envelope protein plays an important role in intracellular trafficking of protein via the cellular secretory pathway. Based on our results it was concluded that a positively charged residue located at either P2 or P4 along with the arginine at P1 is essential for cleavage. PMID- 20591460 TI - Protective properties of non-nucleoside reverse transcriptase inhibitor (MC1220) incorporated into liposome against intravaginal challenge of Rhesus macaques with RT-SHIV. AB - In the absence of an effective vaccine against HIV, it is urgent to develop an effective alternative such as a microbicide. Single and repeated applications of MC1220 microbicide were evaluated in macaques. First, animals were given a single application of 0.5% or 1.5% MC1220-containing liposomal gel. A second group were treated with 0.5% MC1220 once a day for 4 days. The control groups were treated by liposomal gel alone. Thirty minutes after the last application, animals were challenged with RT-SHIV. In the first protocol, 2 of 4 animals treated by 0.5% of the MC1220 and 2 of 5 treated by 1.5% were protected. In the second protocol, 3 of 5 treated animals were protected and 5 of 5 controls were infected. The RNA viral load at necropsy was significantly lower (p=0.05) in treated-infected animals than in controls. In both protocols, the number of CD4+ T cells was lower at viremia peak in infected than in protected animals. PMID- 20591461 TI - Reduction of fecal indicator bacteria (FIB) in the Ballona Wetlands saltwater marsh (Los Angeles County, California, USA) with implications for restoration actions. AB - A benefit of wetland preservation and restoration is the ecosystem service of improving water quality, typically assessed based on bacterial loading. The Ballona Wetlands, a degraded salt marsh of approximately 100 ac located on the southern border of Marina Del Rey (Los Angeles County, California, USA) are currently the focus of publicly funded restoration planning. The wetlands receive tidal water, usually contaminated with fecal indicator bacteria (FIB: total and fecal coliforms, Escherichia coli, enterococci) from the adjacent Ballona Creek and Estuary. During the summer of 2007, two 24-h studies were conducted to determine FIB tidal dynamics within the wetland. Measurements of water flow and mean FIB concentrations (n = 3) were measured every 1.5 h to determine total FIB load estimates. FIB loading rates (MPN/s) were greatest during flood tides as water entered the wetlands, and then again during spring tide conditions when sediments were resuspended during swifter spring ebb flows. During daylight hours, the wetland acted as a sink for these bacteria as loads diminished, presumably by sunlight and other processes. Conversely, during late afternoon and night, the wetlands shifted to being a source as excess FIB departed on ebb flows. Therefore, the wetlands act as both a source and sink for FIB depending on tidal conditions and exposure to sunlight. Future restoration actions would result in a tradeoff - increased tidal channels offer a greater surface area for FIB inactivation, but also would result in a greater volume of FIB-contaminated resuspended sediments carried out of the wetlands on stronger ebb flows. As levels of FIB in Ballona Creek and Estuary diminish through recently established regulatory actions, the wetlands could shift into a greater sink for FIB. PMID- 20591462 TI - Effect of some parameters on the formation of chloroform during chloramination of aqueous solutions of resorcinol. AB - The effects of various factors (N/Cl ratio used to prepare monochloramine, monochloramine doses, pH and contact time) on the monochloramine demand and on the chloroform yield during chloramination of resorcinol have been investigated. Chloramination experiments were carried out at 24+/-1 degrees C, at pH values ranging from 6.5 to 12 using a bicarbonate/carbonate buffer and preformed monochloramine solutions prepared at pH 8.5 with N/Cl ratios ([NH(4)Cl](0)/[Total free Cl(2)](0) ranging from 1.0 to 150 mol/mol). Kinetic experiments ([Resorcinol](0)=5 or 100 microM, [NH(2)Cl](0)/[Resorcinol](0)=20 mol/mol, pH=8.5+/-0.1) showed a slow increase of the monochloramine consumption with reaction time. The monochloramine demands after reaction times of 7 days ([Resorcinol](0)=100 microM) and 14 days ([Resorcinol](0)=5 microM) were equal to 8.5 mol of NH(2)Cl/mole of resorcinol and were higher than the chlorine demands (approximately 7.3 mol/mol). Chloroform yields from monochloramination of resorcinol were lower than 8% (<80 mmol of CHCl(3)/mole of resorcinol) and were less than the yields obtained by chlorination (0.9-0.95 mol/mol). Chloroform productions increased with increasing monochloramine dose and reaction time and decreased with increasing pH values within the pH range 6.5-10. Chloroform formation markedly decreased when the N/Cl ratio increased from 1 to 1.5 mol/mol and was suppressed at N/Cl>100 mol/mol. The data obtained in the present work suggest that free chlorine released from monochloramine hydrolysis plays a significant role on the formation of chloroform during chloramination of resorcinol at N/Cl ratios close to unity (1.00.25 microg/m(3) for ETS) were used to confirm the ETS exposure status of the subject. Concentrations as geometric mean, GM, and standard deviation (GSD) of personal exposures were 0.16 (5.50)microg/m(3) for 3 EP, 0.22 (4.28)microg/m(3) for BUT and 0.09 (3.03)ng/m(3) for benzo(a)pyrene. Concentrations of urinary metabolites were 0.44 (1.70)ng/mL for 1-hydroxypyrene and 0.88 (5.28)ng/mL for cotinine. Concentrations of urinary metabolites of nicotine were lower than in most previous studies, suggesting very low exposures in the ETS-exposed group. Nonetheless, concentrations were higher in the ETS population for cotinine, trans-3'hydroxycotinine, 3-EP, BUT and most high molecular weight PAH, whilst 2-hydroxyphenanthrene, 3+4-hydroxyphenanthrene and 1 hydroxyphenanthrene were only higher in the high-ETS subpopulation. There were not many significant correlations between either personal exposures to PAH and their urinary metabolites, or of the latter with ETS markers. However, it was found that the urinary log cotinine concentration showed significant correlation with log concentrations of 3-EP (R=0.75), BUT (R=0.47), and high molecular weight PAHs (MW>200), especially chrysene (R=0.55) at the p=0.01 level. On the other hand, low correlation was observed between the PAH metabolite 2-naphthol and the parent PAH, gas-phase naphthalene. These results suggest that (1) ETS is a significant source of inhalation exposure to the carcinogen 1,3-butadiene and high molecular weight PAHs, many of which are carcinogenic, and (2) that for lower molecular weight PAHs such as naphthalene, exposure by routes other than inhalation predominate, since metabolite levels correlated poorly with personal exposure air sampling. PMID- 20591484 TI - Anterior segment variations with age and accommodation demonstrated by slit-lamp adapted optical coherence tomography. AB - OBJECTIVE: To investigate anterior segment variations with age and accommodation by slit-lamp-adapted optical coherence tomography (SL-OCT) and determine a safe central vault distance between the implantable contact lens (ICL) and the crystalline lens to avoid contact cataract formation. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Eighty-six patients (126 eyes) under regular review from the Optometry Clinic and Outpatient Department in Zhongshan Ophthalmic Center. METHODS: Patients underwent anterior segment measurements, such as anterior chamber depth (ACD), anterior chamber width (ACW), crystalline lens rise (CLR), and pupil diameter (PD), with the SL-OCT system manufactured by Heidelberg Engineering GmbH, Heidelberg, Germany. Data were analyzed with SPSS software (version 16.0, SPSS, Inc., Chicago, IL). MAIN OUTCOME MEASURES: Anterior segment parameters and their variations with age and accommodation. RESULTS: The internal vertical ACW (V-ACW) was anatomically larger than the internal horizontal ACW (H-ACW). With age, the ACD decreased approximately 17 MUm per year. Forward movement of the crystalline lens' anterior pole decreased approximately 11 MUm per year. During physiologic accommodation, the variation in ACD was -24 MUm per diopter and the alterations in CLR were 28 MUm per diopter. According to our data, a safe lens vault after phakic intraocular lens implantation should be more than 300 MUm to reduce complications. CONCLUSIONS: Slit-lamp-adapted optical coherence tomography is a user-friendly instrument for evaluating the anterior segment, especially for accurate anterior chamber biometry, and may offer guidance on minimizing touch and cataract formation after phakic intraocular lens implantation. PMID- 20591485 TI - Prevalence and causes of low vision and blindness in a rural Southwest Island of Japan: the Kumejima study. AB - PURPOSE: To determine the prevalence and causes of low vision and blindness in an adult population on a rural southwest island of Japan. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: All residents of Kumejima Island, Japan, 40 years of age and older. METHODS: Of the 4632 residents 40 years of age and older, 3762 (response rate, 81.2%) underwent a detailed ocular examination including measurement of the best-corrected visual acuity (BCVA) with a Landolt ring chart at 5 m. The age- and gender-specific prevalence rates of low vision and blindness were estimated and causes were identified. MAIN OUTCOME MEASURES: Low vision and blindness were defined, according to the definition of the World Health Organization, as a BCVA in the better eye below 20/60 to a lower limit of 20/400 and worse than 20/400, respectively. RESULTS: The prevalence of bilateral low vision was 0.58% (95% confidence interval [CI], 0.38-0.89). The primary causes of low vision were cataract (0.11%), corneal opacity (0.08%), retinitis pigmentosa (RP; 0.06%), and diabetic retinopathy (0.06%). The prevalence of bilateral blindness was 0.39% (95% CI, 0.23-0.65). The primary causes of blindness were RP (0.17%) and glaucoma (0.11%). The primary causes of monocular low vision were cataract (0.65%), corneal opacity (0.16%), age-related macular degeneration (0.16%), and diabetic retinopathy (0.11%), whereas those of monocular blindness were cataract (0.29%), trauma (0.25%), and glaucoma (0.22%). Logistic analysis showed that female gender (P = 0.001; odds ratio [OR], 7.37; 95% CI, 2.20-24.71) and lower body weight (P = 0.015; OR, 0.94; 95% CI, 0.90-0.99) were associated significantly with visual impairment. CONCLUSIONS: The prevalences of low vision and blindness in the adult residents of an island in southwest Japan were 1.5 to 3 times higher than the prevalences reported in an urban city on the Japanese mainland. The prevalence of visual impairment caused by RP on this island was much higher than on the mainland, suggesting a genetic characteristic of the population. Furthermore, the prevalence of visual impairment resulting from cataract and corneal opacity was higher than that on the mainland. The prevalence of visual impairment resulting from myopic macular degeneration was less. PMID- 20591486 TI - Development of a diagnostic genetic test for simplex and autosomal recessive retinitis pigmentosa. AB - PURPOSE: Retinitis pigmentosa (RP) causes hereditary blindness in adults (prevalence, approximately 1 in 4000). Each of the more than 30 causative genes identified to date are responsible for only a small percentage of cases. Genetic diagnosis via traditional methods is problematic, and a single test with a higher probability of detecting the causative mutation would be very beneficial for the clinician. The goal of this study therefore was to develop a high-throughput screen capable of detecting both known mutations and novel mutations within all genes implicated in autosomal recessive or simplex RP. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS AND CONTROLS: Participants were 56 simplex and autosomal recessive RP patients, with 360 population controls unscreened for ophthalmic disease. METHODS: A custom genechip capable of resequencing all exons containing known mutations in 19 disease-associated genes was developed (RP genechip). A second, commercially available arrayed primer extension (APEX) system was used to screen 501 individual previously reported variants. The ability of these high-throughput approaches to identify pathogenic variants was assessed in a cohort of simplex and autosomal recessive RP patients. MAIN OUTCOME MEASURES: Number of mutations and potentially pathogenic variants identified. RESULTS: The RP genechip identified 44 sequence variants: 5 previously reported mutations; 22 known single nucleotide polymorphisms (SNPs); 11 novel, potentially pathogenic variants; and 6 novel SNPs. There was strong concordance with the APEX array, but only the RP genechip detected novel variants. For example, identification of a novel mutation in CRB1 revealed a patient, who also had a single previously known CRB1 mutation, to be a compound heterozygote. In some individuals, potentially pathogenic variants were discovered in more than one gene, consistent with the existence of disease modifier effects resulting from mutations at a second locus. CONCLUSIONS: The RP genechip provides the significant advantage of detecting novel variants and could be expected to detect at least one pathogenic variant in more than 50% of patients. The APEX array provides a reliable method to detect known pathogenic variants in autosomal recessive RP and simplex RP patients and is commercially available. High throughput genotyping for RP is evolving into a clinically useful genetic diagnostic tool. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20591487 TI - Incidence of glaucomatous visual field loss: a ten-year follow-up from the Rotterdam Study. AB - PURPOSE: To determine the 10-year incidence of glaucomatous visual field loss (GVFL) and to investigate the influence of risk factors for open-angle glaucoma on this incidence. DESIGN: Population-based cohort study. PARTICIPANTS: Participants aged > or =55 years from the Rotterdam Study. METHODS: Of the 7983 participants in the Rotterdam Study, 6806 underwent ophthalmic examinations at baseline (1990-1993). In 6723 of these 6806 participants (99%), both visual field screening and an assessment of the optic disc were performed. After exclusion of 93 participants with GVFL at baseline, 6630 participants at risk of developing GVFL remained. These participants underwent similar ophthalmic examinations during 2 follow-up visits (1997-1999 and 2002-2006). The incidence of GVFL was determined as an incidence rate and recalculated to a 10-year risk. Risk factors for open-angle glaucoma (age, gender, positive family history of glaucoma, baseline intraocular pressure (IOP), myopia, and baseline vertical cup-to-disc ratio [VCDR]) were assessed using Cox regression. The dependent variable was the development of GVFL. MAIN OUTCOME MEASURES: Ten-year risk and incidence rates of GVFL. Hazard ratios of the above-mentioned risk factors. RESULTS: Of 6630 participants, 3939 (59%) completed at least 1 follow-up examination and 2571 (39%) completed both; 108 participants developed GVFL. The overall incidence rate and 10-year risk of GVFL were 2.9 per 1000 person-years (95% confidence interval [CI], 2.4-3.5) and 2.8% (2.3-3.4), respectively. The 10-year risk increased from 1.9% at age 55 to 59 years to 6.4% at age > or =80 years (P<0.001). The incidence increased by 11% per millimeter of mercury increase in IOP (hazard ratio 1.11; 95% CI, 1.06-1.15). Male gender (1.62; 1.10-2.38), high myopia (spherical equivalent < or =-4 D myopic; 2.31; 1.19-4.49), and a baseline VCDR above the 97.5th percentile (4.64; 2.72-7.91) were associated with the development of GVFL. A positive family history was only significantly associated with the development of GVFL if IOP was removed from the model (2.0; 1.2-3.3; P = 0.012). CONCLUSIONS: These data provide an estimate of the incidence of GVFL in a white population. The development of GVFL was related to higher IOP, older age, high myopia, male gender, a positive family history of glaucoma, and a larger baseline VCDR. PMID- 20591488 TI - Predictors of mortality within 90 days of cataract surgery. AB - PURPOSE: To identify predictors of mortality within 90 days of cataract surgery. DESIGN: A retrospective cohort study. PARTICIPANTS: A total of 45,082 patients who underwent cataract surgery in the Veterans Health Administration (VHA) between October 1, 2005 and September 30, 2007. METHODS: The National Patient (US) Care Database (NPCD) was used to identify all patients who underwent outpatient extracapsular cataract surgery performed in the VHA and who had only 1 cataract surgery within 90 days of the index surgery. Data collected includes demographics, number of hospitalizations within 1 year before surgery, postoperative mortality, and systemic comorbidities using the Charlson Comorbidity Index (CCI), which predicts the 1-year mortality for a patient based on a range of co-morbid conditions scored 1, 2, 3 or 6 depending on the risk of dying associated with the condition. Adjusted odds ratios (OR) of factors predictive of 90-day mortality were calculated using logistical regression modeling. MAIN OUTCOME MEASURES: Mortality within 90 days of cataract surgery. RESULTS: Of the 53,786 patients who underwent cataract surgery during the study period, 45,082 met inclusion criteria. Mean age was 71.8 years; 97.6% were men; 5.0% had complex cataract surgery. The most frequent systemic comorbidities in the CCI were diabetes mellitus (40.6%), chronic pulmonary disease (21.2%), malignant neoplasms (12.5%) and congestive heart failure (CHF; 9.5%). Patients had a median CCI score of 1; 43.7% had a score >= 2. Mortality rate within 90 days after cataract surgery was 7.1 per 1000 patients. Independent predictors of 90-day postoperative mortality were [adjusted OR, (95% confidence interval; CI)]: age 80 or greater [2.54 (1.62, 3.98)], CCI >= 2 [2.06 (1.58, 2.70)], >= 1 hospitalizations in the past year [1.85 (1.45, 2.36)], chronic pulmonary disease (CPD) [1.69 (1.34, 2.14)], CHF [1.71 (1.29, 2.14)], cirrhosis [2.60 (1.31, 5.15)], multiple myeloma or leukemia [2.20 (1.07, 4.53)], and metastatic solid tumor [4.17 (1.80, 9.66)]. CONCLUSIONS: The risk of 90-day mortality after cataract surgery is low, even for patients at higher risk for mortality such as the elderly and those with a high preoperative disease burden. PMID- 20591489 TI - Muller's muscle: a component of the peribulbar smooth muscle network. AB - PURPOSE: To examine Muller's muscle's horizontal extensions in relation to the peribulbar smooth muscle network. DESIGN: Observational anatomic study. PARTICIPANTS: Twenty postmortem orbits (10 right, 10 left) of 15 Asians (8 males, 7 females; age range at death, 61-93 years; mean age, 78.4 years) fixed in 10% buffered formalin. METHODS: After performing a full-thickness 360 degrees incision of the periosteum around the circumference of the orbit, the periosteum was elevated and finally detached near to the orbital apex. Nerves, blood vessels, and the nasolacrimal duct arising from the orbital wall were cut. The lateral orbital wall then was removed at approximately 3 cm posterior to the orbital rim and the retrobulbar content was incised with a sharp scalpel in a coronal plane. The removed orbital content was incised at a plane passing from a point located 15 mm superior to the upper eyelid margin and the globe equator at 3- and 9-o'clock areas. The sliced specimens were dehydrated and embedded in paraffin, cut into 7-MUm thickness sections, and then stained with Masson trichrome. MAIN OUTCOME MEASURES: The medial and lateral extensions of Muller's muscle in relation to the peribulbar smooth muscle network. RESULTS: In all specimens, Muller's muscle extended medially and laterally. The medial extension reached the medial rectus muscle pulley, which is rich in smooth muscle fibers. The lateral extension reached the lateral rectus muscle pulley by passing through the lacrimal gland fascia of the palpebral lobe, in which 12 specimens also showed a direct extension to the lateral rectus muscle pulley in the posterior part. CONCLUSIONS: Muller's muscle has a medial and a lateral extension to the peribulbar smooth muscle network. These new findings indicated that Muller's muscle is not an independent structure in the upper eyelid, but rather a component of the peribulbar smooth muscle network. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20591490 TI - A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. AB - PURPOSE: To evaluate the visual outcome, number of injections, and direct medical cost of a "treat and extend" regimen (TER) in managing neovascular age-related macular degeneration (nAMD) with intravitreal ranibizumab. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: Ninety-two eyes of 92 patients met the entry criteria from May 2006 to May 2008. METHODS: All patients with treatment-naive nAMD were treated monthly until no intraretinal or subretinal fluid was observed on optical coherence tomography (OCT). The treatment intervals were then sequentially lengthened by 2 weeks until signs of exudation recurred. The interval was individualized for each patient in an attempt to maintain an exudation-free macula. MAIN OUTCOME MEASURES: Change from baseline visual acuity, proportion of eyes losing < 3 lines and gaining >= 3 lines at 1 year of follow-up, annual mean number of injections, change from baseline OCT central retinal thickness (CRT), maximum period of extension, and adverse ocular and systemic events. RESULTS: The mean follow-up was 1.52 years. Mean Snellen visual acuity improved from 20/135 at baseline to 20/77 at 1 year follow-up (P < 0.001) and 20/83 at 2 years follow-up (P = 0.002). The proportion of eyes that lost < 3 Snellen visual acuity lines at final follow-up was 96% and the proportion that gained >= 3 Snellen visual acuity lines was 32%. The mean OCT CRT decreased from 303 MUm at baseline to 238 MUm at 1 year follow-up (P < 0.001). The mean number of injections over the first year and between years 1 and 2 was 8.36 and 7.45, respectively. The mean maximum period of extension was 79.9 days. No adverse ocular or systemic events were reported during the follow-up period. The direct annual medical cost per patient was $16,114.52 for the TER. The direct annual medical cost per patient ranged from $15,880.07 to $28,314.16 based on previous clinical trial protocols. CONCLUSIONS: Eyes with nAMD experienced significant visual improvement when managed with intravitreal ranibizumab using a TER. This treatment approach also was associated with significantly fewer patient visits, injections, and direct annual medical cost compared with monthly injections such as in the phase III clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 20591491 TI - Clinical characteristics and visual outcome of severe ocular chemical injuries in Shanghai. AB - OBJECTIVE: To study the clinical characteristics of patients with severe ocular chemical injury in Shanghai and to determine their relationship with visual outcome. DESIGN: Retrospective case series. PARTICIPANTS: A total of 79 525 in patients at Shanghai Eye, Ear, Nose, and Throat Hospital between 1998 and 2008. METHODS: Medical records of severe ocular chemical injuries were reviewed retrospectively. Patients' age, gender, occupation, location where injury occurred, the nature of chemical agent, complication, and visual acuity at final follow-up were described. The relationship between visual impairment and clinical characteristics was analyzed. MAIN OUTCOME MEASURES: Estimated prevalence rate, demographics of patients, nature of injury, prognosis, and factors associated with visual impairment. RESULTS: The estimated prevalence rate in Shanghai of severe ocular chemical injury was 1.58 per 100,000. One hundred ninety cases with 239 eyes were identified for analyzing the clinical characteristics. The average age of all subjects was 35.3 +/- 14.8 years with a male:female ratio of 6:1. Factory and construction worker (n = 141; 74.2% of total cases) were the most common occupations. Most of the accidents occurred at workplace (n = 144; 74.8%); the majority of injuries were caused by alkali agents (n = 129; 67.9%). Complications were found in 222 eyes (92.9%). A visual acuity of >= 6/60 was achieved only in 5 eyes (2.1%). In multivariate logistic regression analysis, being visually impaired was significantly associated with the patients' complication (P = 0.021). CONCLUSIONS: The prevalence of severe ocular chemical injury in Shanghai is low. Most subjects needed surgery to restore visual function. Successful management provides a good prognosis for most patients. PMID- 20591492 TI - Topical imiquimod for periocular lentigo maligna. AB - PURPOSE: To evaluate the efficacy of topical imiquimod 5%, a local immune response modifier, in the treatment of periocular lentigo maligna. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Five consecutive patients with biopsy-proven periocular lentigo maligna. METHODS: Periocular lentigo maligna was treated with topical imiquimod 5%. The clinical features, treatment schedule, response to treatment, and complications were analyzed retrospectively. MAIN OUTCOME MEASURES: Response to treatment and complications. RESULTS: The mean patient age was 73 years. The anatomic location of lentigo maligna was the medial canthal area in 2 patients, the lateral canthal area in 1 patient, and the lower eyelid in 2 patients. Topical imiquimod 5% was used for 5 days per week in 3 patients and for 7 days per week in 2 patients. The medication was placed only on the skin and not the globe. The mean duration of treatment was 9 months (range, 1-14 months). Lentigo maligna partially resolved in 3 patients and completely resolved in 2 patients. The most common side effects included localized erythema and discomfort (n = 4), swelling (n = 3), and cutaneous excoriation (n = 2). There were no patients with toxicity to the conjunctiva, cornea, or globe. Treatment was discontinued in 2 patients (one temporarily and the other permanently) because of intolerable local side effects of discomfort, redness, swelling, and cutaneous excoriation. There was no recurrence of lentigo maligna in those with complete or partial response (mean follow-up, 20 months). CONCLUSIONS: Periocular lentigo maligna seems to respond to topical imiquimod 5% treatment. Topical imiquimod 5% treatment for periocular lentigo melanoma deserves further study. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 20591493 TI - Trends in fungal keratitis in the United States, 2001 to 2007. AB - OBJECTIVE: Fungal keratitis is a serious ocular infection that is considered to be rare among contact lens wearers. The recent Fusarium keratitis outbreak raised questions regarding the background rate of Fusarium-related keratitis and other fungal keratitis in this population. DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Six hundred ninety-five cases of fungal keratitis cases who presented to 1 of 10 tertiary medical centers from 2001 to 2007. METHODS: Ten tertiary care centers in the United States performed a retrospective review of culture-positive fungal keratitis cases at their centers between January 2001 and December 2007. Cases were identified using microbiology, pathology, and/or confocal microscopy records. Information was collected on contact lens status, method of diagnosis, and organism(s) identified. The quarterly number of cases by contact lens status was calculated and Poisson regression was used to evaluate presence of trends. The Johns Hopkins Medicine Institutional Review Board (IRB) and the IRBs at each participating center approved the research. MAIN OUTCOME MEASURES: Quarterly number of fungal keratitis cases and fungal species. RESULTS: We identified 695 fungal keratitis cases; 283 involved the use of contact lenses. The quarterly number of Fusarium cases increased among contact lens wearers (CLWs) during the period that ReNu with MoistureLoc (Bausch & Lomb, Rochester, NY) was on the market, but returned to prior levels after withdrawal of the product from the market. The quarterly frequency of other filamentous fungi cases showed a statistically significant increase among CLWs comparing October 2004 through June 2006 with July 2006 through December 2007 with January 2001 through September 2004 (P < 0.0001). CONCLUSIONS: The quarterly number of Fusarium fungal keratitis cases among CLWs returned to pre-Renu with Moistureloc levels after removal of the product from the market. However, the number of other filamentous fungal keratitis cases, although small, seems to have increased among refractive CLWs. Reasons for these apparent increases are unclear. PMID- 20591494 TI - Obsessive-compulsive disorder and cyclothymic temperament: an exploration of clinical features. AB - BACKGROUND: Bipolar disorder comorbidity in obsessive-compulsive disorder (OCD) has relevant implications on the symptomatological expression, complications and pharmacologic treatment of the disorder. Relatively few data exist on OCD comorbid with soft-bipolar forms. The aims of the study are to evaluate affective temperaments in patients with OCD and to analyze differences in socio-demographic and clinical characteristics according to the presence or absence of cyclothymic temperament. METHODS: The sample consisted of 167 patients with a principal diagnosis of OCD (DSM-IV-TR). Affective temperaments have been evaluated through the Italian semistructured interview version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-I). RESULTS: A total of 90 patients (53.9%) were diagnosed with a dominant affective temperament. Cyclothymic affective temperament (CT) was the most represented in the sample of OCD patients (19.2%). Patients with CT showed significant lower mean age at onset, higher scores at the HAM-A, more repeating compulsions, higher rates of eating disorder comorbidity, OCD spectrum disorder comorbidity and higher rates of Axis II comorbidity (particularly Cluster A). LIMITATIONS: Recruitment of OCD patients from a tertiary center. Absence of an investigation about treatment implications associated with cyclothymic temperament. CONCLUSIONS: Patients with OCD and CT could be more severe and complicated compared to patients without CT. Moreover, individuals with OCD spectrum disorders may be vulnerable to bipolarity. Systematic assessment of affective temperament is necessary to detect OCD with such a soft-bipolar comorbidity. PMID- 20591495 TI - Unplanned versus planned suicide attempters, precipitants, methods, and an association with mental disorders in a Korea-based community sample. AB - BACKGROUND: Studies have consistently reported that a considerable proportion of suicidal attempts are unplanned. We have performed the first direct comparison between planned and unplanned attempts including associated methods and precipitants. METHOD: A total of 6510 adults, who had been randomly selected through a one-person-per-household method, completed interviews (response rate 81.7%). All were interviewed using the K-CIDI and a questionnaire for suicide. RESULTS: Two hundred and eight subjects reported a suicide attempt in their lifetime, one-third of which had been unplanned. These individuals exhibited a lower level of education; however, no significant differences were found with regard to age, gender, marital and economic status. Further, 84.0% of unplanned attempters experienced previous suicidal ideation, experiencing their first attempt 1.9 years before ideation. Additionally, 94.4% of unplanned attempters had precipitants for attempts such as familial conflict and it was also found that methods such as the use of chemical agents or falling were three times more common in unplanned than planned attempters. With respect to unplanned attempters, they exhibited a significant association with alcohol use disorder, major depressive disorder, posttraumatic stress disorder, and bipolar disorder. In particular, bipolar disorder was found to be 3.5 times higher in these individuals. CONCLUSIONS: Results have revealed that unplanned suicide attempters experience suicidal ideation and precipitants prior to their attempt. Further, attempts were associated with affective and alcohol use disorders. Therefore, in order to reduce the number of suicidal attempts, it may be useful to evaluate suicidal ideation concurrent to the treatment of existing mental disorders. PMID- 20591496 TI - Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis. AB - Experimental autoimmune orchitis (EAO) with experimental autoimmune epididymitis (EAE) can be induced in mice by immunization with testicular antigens emulsified in adjuvants. On immunization with syngeneic testicular germ cells (TGC) alone, EAO with no EAE is induced in mice. Recently, we found that EAE with no EAO can be induced in vasectomized mice by immunization with TGC. In the present study, we investigated the appearance of autoantigens relevant to EAO and EAE by reacting each immune serum sample with testes and epididymides extracts from normal mice of various ages by immunoblotting. The results showed that the antisera obtained from mice with EAO lesions specifically defined testicular antigens with molecular weights of 15 kDa, 40 kDa, 75 kDa and >200 kDa from 4 weeks of age, but the antisera obtained from mice with EAE strongly defined both testicular and epididymal antigens of 25 kDa from 5 and 8 weeks of ages, respectively. These results suggest that vasectomy changes the target autoantigens in TGC-induced autoimmunity. PMID- 20591497 TI - Soluble CD30 in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women. AB - This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction. PMID- 20591498 TI - How do eating disorder specialist clinicians apply DSM-IV diagnostic criteria in routine clinical practice? Implications for enhancing clinical utility in DSM-5. AB - The clinical utility of the DSM-IV eating disorder (ED) diagnostic criteria among practicing clinicians has not been formally evaluated, despite the considerable diagnostic challenges these disorders present. This study evaluated inter-rater reliability between research and clinical diagnoses, identified discrepantly rated diagnostic criteria, and evaluated ED subtype use in a naturalistic treatment setting. Seventy-six adolescent and young adult female patients consecutively admitted to a residential ED program were evaluated independently by clinicians (unstructured clinical interview) and research assessors (Structured Clinical Interview for DSM-IV). Clinicians and research assessors conferred concordant ED diagnoses in 80.3% of cases (kappa=0.70), thus highlighting the clinical utility of the extant DSM-IV diagnostic scheme in this specialty ED treatment setting. All but two discordant cases included a diagnosis of ED not otherwise specified (EDNOS). Clinicians applied ED subtypes in just 20.4% of eligible cases, and were significantly more likely to apply subtypes to major depressive disorder. Although clinical and research interviews yielded substantial reliability, EDNOS had the lowest reliability among the ED diagnoses. Moreover, infrequent subtype application on this specialty unit raises questions about the clinical utility of DSM-IV anorexia nervosa and bulimia nervosa subtypes, even in the context of clinically useful overarching categories. PMID- 20591499 TI - Catechol-O-methyltransferase Val158Met polymorphism and negative symptoms after acute antipsychotic treatment in first-episode non-affective psychosis. AB - Genetic factors play an important role in the understanding of clinical response to antipsychotic treatments. We aimed to assess the effect of the catechol-O methyltransferase (COMT) genotype in the short-term (6 weeks) clinical response of 161 first-episode psychosis patients. COMT genotype was not related to clinical response at 6 weeks. Val homozygote patients showed higher negative symptoms than Met homozygote patients. The COMT Val158 genotype seems to be related to the severity of negative symptoms rather than to clinical response. PMID- 20591500 TI - Aberrant autophosphorylation of c-Kit receptor in canine mast cell tumor cell lines. AB - Several studies indicated that KIT mutation could cause ligand-independent activation of c-Kit receptor in canine mast cell tumor (MCT). The objective of this study was to investigate mechanisms of c-Kit receptor activation in various canine MCT cell lines. Four cell lines, HRMC (derived from cutaneous MCT), VIMC1 (visceral MCT), CoMS1 (visceral MCT) and CMMC1 (cutaneous MCT), were cultured in stem cell factor (SCF, a ligand of c-Kit receptor)-free medium and subjected to analyses of KIT mutation, c-Kit receptor phosphorylation, SCF expression and the effects of SCF stimulation. In addition, the SCF/c-Kit receptor autocrine mechanism was verified in HRMC cells. HRMC cells expressed wild type c-Kit receptor. Both VIMC1 and CoMS1 cells had the same one amino acid (AA) substitution in the extracellular domain of c-Kit receptor. CMMC1 cells had at least three variants of c-Kit receptor such as one AA deletion in the extracellular domain (variant A), one AA substitution in the extracellular domain as well as an internal tandem duplication in the juxtamembrane domain (variant B), and a nonsense mutation (variant C). Both mature and immature forms of c-Kit receptor were observed and the c-Kit receptors were phosphorylated in all cell lines. While both mature and immature forms of c-Kit receptor were substantially phosphorylated in CMMC1 cells, the immature form was slightly phosphorylated in other cell lines. Phosphorylation of c-Kit receptor in HRMC, VIMC1 and CoMS1 cells were enhanced by SCF stimulation whereas no enhancement was observed in CMMC1 cells. There was no effect of SCF stimulation on proliferation of all the cell lines. SCF protein was detectable in only HRMC cells although mRNA expression of SCF was detected in all the cell lines. A tyrosine kinase inhibitor Dasatinib (internal inhibitor) inhibited c-Kit receptor phosphorylation in HRMC cells whereas anti-canine SCF antibody (external inhibitor) had no inhibitory effect. Thus there could be no external SCF/c-Kit receptor autocrine mechanism whereas there could be an internal autocrine mechanism within HRMC cells. The results indicated that consistent c-Kit receptor phosphorylation could be caused by the stimulation with autocrine SCF in HRMC cells while it could be caused by functional mutations of KIT in VIMC1, CoMS1 and CMMC1 cells. As the four canine MCT cell lines had various aberrations associated with c-Kit receptor phosphorylation, KIT mutation and SCF expression, such molecular biological diversity might reflect the different biological behavior in canine MCT. PMID- 20591501 TI - Cloning, expression and bioactivity of BAFF from Petaurus breviceps. AB - B-cell activating factor (BAFF), belonging to the TNF (tumor necrosis factor) family, is crucial for B-cell survival and maturation. In the present study, PbBAFF cDNA was amplified from the sugar glider Petaurus breviceps by RT-PCR and RACE (rapid amplification of cDNA ends) strategies. The open reading frame (ORF) of PbBAFF cDNA encodes a protein consisting of 287-amino acid. The deduced amino acid sequence contains a predicted transmembrane domain, a putative furin protease cleavage site, a potential N-glycosylation site and conserved cysteine residues similar to that identified in other mammalian BAFF. The soluble mature part of PbBAFF (PbsBAFF) showed 88-92% sequence identity with mammalian homologs. The predicted three-dimensional (3D) structural analysis of PbsBAFF analyzed by comparative protein modeling revealed that they are very similar to the 3D structure of human BAFF. Recombinant PbsBAFF fused with His(6) tag was efficiently expressed in Escherichia coli BL21 (DE3). In vitro, purified PbsBAFF co-stimulates the proliferation of human B-cells. These findings indicate PbBAFF, the first BAFF cloned from marsupial, plays an important role in proliferation of B-cells, and phylogenetic analyses reveal that the work is of value with respect to continued refinement of our understanding of mammalian phylogenetic relationships. PMID- 20591502 TI - Distinct reactivities of interleukin-4-specific antibodies with recombinant and native canine interleukin-4 in various assays. AB - Interleukin 4 (IL-4) plays a central role in immune responses to parasites and allergens. IL-4 drives the differentiation of naive T cells into Th2 cells and regulates immunoglobulin class switching to IgE.Little is known about the role of IL-4 in canine allergies and parasite infections. Most of the information derives from measurement of IL-4 mRNA expression in dog tissues, but detection of IL-4 protein has been difficult so far, probably due to low sensitivity of available methods. Antibodies (Ab) specific for canine IL-4 are available from various sources, but these Ab have been produced against recombinant Escherichia coli expressed canine IL-4 and there is only limited information on their reactivities with native canine IL-4. Therefore, in the present study, we tested six available canine IL-4-specific Ab for their reactivities with recombinant canine IL-4 expressed in E. coli (rec.IL-4) or in mammalian cells (mam.IL-4), and with supernatants from stimulated canine peripheral blood mononuclear cells (PBMCs) using several detection methods, including Western blotting, ELISA, cytokine bead assay, and intracellular IL-4 staining. Additionally, we tested a bovine IL-4 specific antibody that has been previously shown to cross-react with canine IL-4. All tested Ab except anti-bovine IL-4 reacted with rec.IL-4, and most of them reacted with mam.IL-4. However, only the cytokine bead assay was sensitive enough to allow the detection of IL-4 in supernatants of canine PBMCs. PMID- 20591503 TI - Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species. AB - Mannheimia haemolytica infection results in enhanced PMN-mediated tissue damage in the lungs of bighorn sheep (BHS) compared to that of domestic sheep (DS). SERPIN B1 is an inhibitor of PMN-derived serine proteases. It prevents lung tissue injury by inhibiting the serine proteases released as a result of PMN lysis and degranulation. It is conceivable that PMNs of BHS exhibit decreased quantity and/or activity of SERPIN B1 which results in enhanced tissue injury and decreased bacterial clearance in pneumonic lungs of BHS. The objective of this study was to clone and express SERPIN B1 of BHS and DS, and develop antibodies to facilitate quantification of SERPIN B1. The 1,134bp cDNA of SERPIN B1 of BHS and DS encodes a polypeptide of 377 amino acids. SERPIN B1 of BHS and DS exhibits 100% identity at the nucleotide and amino acid levels. The amino acid sequence of ovine (BHS/DS) SERPIN B1 displays 69%, 71%, 74%, 78% and 80% identity with that of rats, dogs, mice, humans and horses, respectively. Ovine SERPIN B1 expressed in Escherichia coli was used to develop polyclonal antibodies in mice. Western blot analysis revealed the specificity of these antibodies for ovine rSERPIN B1. PMID- 20591504 TI - Ultra-early weaning in piglets results in low serum IgA concentration and IL17 mRNA expression. AB - In pigs raised for meat production, weaning is a critical period because of related physiological perturbations and negative consequences on performance. Previous studies have shown that early weaning could either impair development of mucosal barrier function or boost intestinal immunologic parameters. In order to obtain further knowledge about the impact of ultra-early weaning on the porcine immune system development, three groups of piglets were weaned at different ages and compared to the unweaned control group. Lower IgA concentrations in ultra early and early weaned piglets than in other piglets were identified in serum. In the mesenteric lymph node (MLN), significant differences in the mRNA expression of IL17a, TGF beta and FOXP3 were found between specific groups. Indeed, IL17a mRNA was mainly detected in ultra-early weaned piglets while FOXP3 and TGF beta mRNA were associated to both ultra-early weaned and suckling piglets. Reduced serum IgA concentration and MLN induction of a Th17 cytokine in ultra-early weaned piglets could be related to alterations of the mucosal barrier functions consecutive to the milk deprivation. All together, our findings suggest a crucial role for endogenous milk factors onto the onset of IgA synthesis. PMID- 20591505 TI - Is hearing loss a feature of Joubert syndrome, a ciliopathy? AB - OBJECTIVE: To assess if hearing loss is a feature of Joubert syndrome (JBS), one of the ciliopathies and therefore possibly associated with hearing loss. DESIGN: Retrospective case series. SETTING: University Children's Hospital. PATIENTS: Dutch patients with JBS. MAIN OUTCOME MEASURES: Audiological data. RESULTS: Data from 22 Dutch Joubert syndrome (JBS) cases (17 males, 5 females) aged 3-40 years were available. Audiological tests were successfully performed in 14 cases. Three cases (aged 17-26 years) showed very mild sensorineural hearing loss (SNHL) at different frequencies. Conductive hearing loss due to middle ear infections occurred frequently in young JBS children (6 out of 22 cases). In three cases (aged 3-13 years) the parents reported the child was hypersensitive to sound. CONCLUSION: We found no evidence for significant hearing loss in Joubert syndrome patients. However, given the compromised speech development in JBS, conductive hearing loss due to middle ear infections should be treated vigorously. SNHL at a later age cannot be excluded on the basis of our data, given the sample size. Three of the older cases showed discretely increased hearing thresholds. Analogous to the ciliopathy Bardet-Biedl syndrome, where hearing thresholds were reported to be subclinically increased in a group of adolescents patients, we recommend follow-up of JBS patients in view of the possibility of progressive, late-onset SNHL. PMID- 20591506 TI - V-Y two-layer repair for oronasal fistula of hard palate. AB - OBJECTIVE: Oronasal fistula represents a functional problem after cleft palate repair; its closure is technically difficult with a high recurrence rate after primary treatment. The aim of this study was to evaluate the efficacy of closure of oronasal fistula using 2 layers of oral mucoperiosteum in a V-Y manner. METHODS: Fourteen patients were subjected for repair of their oronasal fistulas using 2 layers; the first is the oral mucoperiosteum that is elevated and inverted to close the nasal side as a hinge flap, and the second is also the oral mucoperiosteum that is elevated and sutured in a V-Y manner to close the oral side. RESULTS: In all cases, the fistula was completely closed at first attempt, no cases developed operative or postoperative complications. Recurrence with not recorded in any case after a follow-up period of at least 12 months. CONCLUSION: Closure of oronasal fistula of the hard palate that may develop after cleft palate repair using a two-layer closure in V-Y manner is an easy and ideal method with a high success rate. PMID- 20591507 TI - Extending the chinchilla middle ear epithelial model for mucin gene investigation. AB - OBJECTIVES: To investigate the expression of recently identified human mucin genes in an in vivo model of the chinchilla middle ear epithelium (CMEE). METHODS: CMEE was harvested, RNA was extracted and primers were designed for RT PCR to assess for expression of mucin genes Muc6, Muc17 and Muc18. Further sequencing of these genes was also accomplished. RESULTS: Mucin genes Muc6, Muc17 and Muc18 was assessed and found to be identical to the expression in human and mouse MEE. CONCLUSION: This study further characterizes mucin gene expression in the CMEE and provides additional sequence data for chinchilla middle ear genes. The concordance of this gene expression data to that of both the human and mouse models further demonstrates the utility of this animal model in OM investigations. PMID- 20591508 TI - Exploring the chemical space of gamma-secretase modulators. AB - gamma-Secretase is a key enzyme in the pathophysiology of Alzheimer's disease (AD) and is responsible for the production of potentially toxic amyloid-beta (Abeta) 42 peptides. gamma-Secretase modulators (GSMs) are small molecules (<600 Da) causing a product shift from Abeta42 toward shorter and less toxic Abeta fragments. Classical non-steroidal anti-inflammatory drugs (NSAIDs) constituted the first class of GSMs, and therefore many of today's GSMs exhibit NSAID-like overall structure combining an acidic head group with a lipophilic backbone. Recent developments include structurally different non-acidic GSMs. Here we summarize common structural features of GSMs, pick up the controversial discussion regarding their mechanism of action, and show how computational analysis of pharmacophoric features can help reveal their pharmacological profile. PMID- 20591509 TI - Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications. AB - Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. PMID- 20591511 TI - Anti-depressants make amphipods see the light. AB - The effects of serotonin altering parasites, serotonin, the anti-depressant fluoxetine, plus two other highly prescribed pharmaceuticals (carbamazepine and diclofenac) on the behaviour of the marine amphipod, Echinogammarus marinus were investigated. Acanthocephalan parasites are known to alter the swimming behaviour in their amphipod hosts through changes in serotonergic activity resulting in increased predation. Behavioural assays were adapted to record changes in phototaxis and geotaxis behaviour in male E. marinus following 7, 14 and 21 days exposure to serotonin and each pharmaceutical compound at 4 concentrations compared to a control (between 10 ng/L and 10 microg/L). E. marinus infected with acanthocephalans parasites had both significantly higher phototaxis and geotaxis scores than those of uninfected specimens. Phototaxis and geotaxis behaviour increased significantly in a concentration-dependent manner with exposure to serotonin. Fluoxetine significantly altered phototaxis and geotaxis activity in what appeared to be a non-monotonic concentration response curve with the greatest behavioural changes observed at 100 ng/L. The main patterns of these behavioural responses were consistent between two trials and the 3 weeks exposure with specimens spending more time within the light and occurring higher in the water column. No obvious trends could be concluded in the phototaxis and geotaxis scores from individuals exposed to carbamazepine or diclofenac as might be expected from their known mode of action. From this study phototaxis and geotaxis behaviour have been observed to be affected by exposure to serotonin modulators. Parasite studies have shown strong links between changes in behaviour and increased predation risk correlating with changes in serotonergic activity. This study has highlighted the potential for highly prescribed anti-depressant drugs to change the behaviour of an ecologically relevant marine species in ways which could conceivably lead to population level effects. PMID- 20591512 TI - Prevalence of high ankle-brachial index (ABI) in general population of Southern Italy, risk factor profiles and systemic cardiovascular co-morbidity: an epidemiological study. AB - Many studies have been carried out to assess the prevalence, risk factors and co morbidities of peripheral artery disease (PAD). By contrast, to date there is a lack of data on patients with high-ABI. This study aimed at estimating the prevalence of increased ABI (ABI>1.4) and to evaluate the involvement of traditional cardiovascular (CV) risk factors and the atherosclerotic burden (peripheral and carotid arteries) of these patients in a population of Southern Italy. We invited 9647 subjects, age ranging from 30 to 80, by letters to undergo an ABI measurement. Consequently, in patients with ABI>1.4, an ultrasound evaluation of the peripheral and carotid arteries was performed. An ABI>1.4 was found in 260 of 3412 subjects (7.6%). Statistically significant differences were reported in age, diabetes and hypertension, body mass index (BMI) and waist circumference (WC). No differences in sex distribution, dyslipidemia and smoke prevalence were observed. Moreover, 67.9% of ABI>1.4 patients showed a peripheral intima-media thickness (IMT)>0.9 mm; at linear regression it was correlated with ABI values; 25% of patients showed peripheral plaques. A carotid IMT>0.9 mm was reported in 78.6% of high-ABI patients and 32.1% were affected by atherosclerotic plaques. The observed increased-ABI prevalence of 7.6% was higher than previously reported. This was more prevalent in an older population with diabetes, hypertension and obesity. Moreover, these patients are characterized by an extended atherosclerotic involvement. Further studies are needed to clarify this evidence, a longitudinal observation of this clinical outcome, as we are performing, could provide a number of interesting elements. PMID- 20591510 TI - Do cannabinoids have a therapeutic role in transplantation? AB - Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties. Significant clinical and experimental data on the use of cannabinoids as anti inflammatory agents exist in many autoimmune disease settings, but virtually no studies have been undertaken on their potential role in transplant rejection. Here we suggest a theoretical role for the use of cannabinoids in preventing allograft rejection. The psychotropic properties of CB1 agonists limit their clinical use, but CB2 agonists may offer a new avenue to selectively target immune cells involved in allograft rejection. Moreover, development of mixed CB1/CB2 agonists that cannot cross the blood-brain barrier may help prevent their undesired psychotropic properties. In addition, manipulation of endocannabinoids in vivo by activating their biosynthesis and inhibiting cellular uptake and metabolism may offer another pathway to regulate immune response during allograft rejection. PMID- 20591513 TI - An unusual cause of acute pulmonary embolism. PMID- 20591514 TI - Hypothermia after cardiac arrest should be further evaluated--a systematic review of randomised trials with meta-analysis and trial sequential analysis. AB - BACKGROUND: Guidelines recommend mild induced hypothermia (MIH) to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. Our objective was to systematically evaluate the evidence for MIH taking into consideration the risks of systematic and random error and to GRADE the evidence. METHODS: Systematic review with meta-analysis and trial sequential analysis of randomised trials evaluating MIH after cardiac arrest in adults. We searched CENTRAL, MEDLINE, and EMBASE databases until May 2009. Retrieved trials were evaluated with Cochrane methodology. Meta-analytic estimates were calculated with random- and fixed-effects models and random errors were evaluated with trial sequential analysis (TSA). RESULTS: Five randomised trials (478 patients) were included. All trials had substantial risk of bias. The relative risk (RR) for death was 0.84 (95% confidence interval (CI) 0.70 to 1.01) and for poor neurological outcome 0.78 (95% CI 0.64 to 0.95). For the two trials with least risk of bias the RR for death was 0.92 (95% CI 0.56 to 1.51) and for poor neurological outcome 0.92 (95% confidence interval 0.56 to 1.50). TSA indicated lack of firm evidence for a beneficial effect. The substantial risk of bias and concerns with directness rated down the quality of the evidence to low. CONCLUSIONS: Evidence regarding MIH after out-of-hospital cardiac arrest is still inconclusive and associated with non-negligible risks of systematic and random errors. Using GRADE-methodology, we conclude that the quality of evidence is low. Our findings demonstrate that clinical equipoise exists and that large well designed randomised trials with low risk of bias are needed. PMID- 20591515 TI - Impact of plaque morphology on creatine kinase-MB elevation in patients with elective stent implantation. AB - BACKGROUNDS: The association between percutaneous coronary intervention (PCI) and subsequent myonecrosis has been widely recognized, and worse prognosis has been reported among patients with elevated post-PCI biomarkers. We used optical coherence tomography (OCT) to study the relationship between pre-PCI plaque morphology and post-PCI creatine kinase-MB (CK-MB) elevation. METHODS: One hundred and twenty-five patients with normal pre-PCI CK-MB levels underwent OCT examination before nonemergency stent implantation. Patients were divided into two groups according to the presence (Group CK, n=35) or absence (Group NCK, n=90) of post-PCI CK-MB elevation >= upper limit of the normal range. Clinical and the OCT findings were compared between the two groups. RESULTS: Elevated CK MB levels was observed in 35 patients (28%). The CK-MB elevation was associated with elevated white blood cell count, type B2/C lesions, the presence of thin cap fibroatheroma (TCFA), plaque rupture, and lipid quadrants. In the multivariate analysis, the presence of TCFA (OR 4.68, 95% CI 1.88-11.64, p=0.001) and type B2/C lesions (OR 4.20, 95% CI 1.30-13.59, p=0.02) were independent predictors of post-PCI CK-MB elevation. CONCLUSIONS: TCFA and angiographically complex lesion morphology can predict post-PCI CK-MB elevation in patients treated with elective stent implantation. OCT may be useful in stratifying the risk for nonemergency stent implantation. PMID- 20591516 TI - Effects of B-Blockers on outcome of patients with Chagas' cardiomyopathy with chronic heart failure. AB - BACKGROUND: A few studies have shown a beneficial effect of B-Blocker therapy on cardiac function and functional status in patients with chronic heart failure secondary to Chagas' cardiomyopathy. METHODS: The medical charts of patients routinely followed from January, 2000 to January, 2007 were reviewed to collect clinical, standard laboratory tests, 12-lead electrocardiogram, chest X-Ray, and Doppler echochardiogram variables. A Cox proportional hazards model was used to establish independent predictors of all-cause mortality for patients with Chagas' cardiomyopathy with chronic heart failure. RESULTS: A total of 231 consecutive patients were enrolled in the study. Median follow up was 19 (7, 46) months. Twenty (9%) patients underwent heart transplantation and 120 (52%) died during the investigation. Left ventricular systolic dimension (hazard ratio=1.04; 95% confidence interval=1.02 to 1.06; p<0.005) and need of inotropic support (hazard ratio=1.80; 95% confidence interval 1.2 to 2.60; p=0,03), were positively associated, whereas B-Blocker therapy (HR=0.34; 95% confidence interval 0.23 to 0.51; p<0.0005) was negatively associated with mortality. Mortality was significantly lower in patients taking in comparison to those not taking B Blockers. Patients taking a mean daily dose of carvedilol>or=to 9.375mg had a marked decrease in mortality in comparison to those not on carvedilol therapy. CONCLUSION: B-Blockers are effective, not detrimental, and may improve survival in Chagas' disease patients with chronic heart failure. A randomized trial is necessary to confirm these findings. PMID- 20591517 TI - Influence of repeat-service and weaning-to-first-service interval on farrowing proportion of gilts and sows. AB - The present study was performed to evaluate different components of reproductive failure after service under a tropical climate and to investigate the influence of repeat-service and delayed wean-to-service interval (WSI) on subsequent fertility in gilts and sows. The study was conducted in four commercial swine breeding herds in the northeastern part of Thailand. Data were collected during a 3-year period from July 2005 to June 2008. A total of 30,058 insemination records from 9037 gilts and sows was included. On average, the farrowing proportion (FP) was 81.9% and adjusted FP (excluding gilts/sows culled after service) was 85.3%. The reasons for the failure to farrow included return-to-oestrus 9.4%, abortion 1.7%, not being pregnant 1.0% and not-in-pig 2.0%. Non-repeat-service females had 83.7% FP, while those that experienced repeat-serviced for 1, 2 and > or = 3 times had 71.2%, 57.7% and 43.4% FP, respectively (P<0.001). The seasonal influence on FP was observed in non-repeat-serviced females, but not in those that experienced repeat-service. Sows mated during 0-6 days after weaning had 86.8% FP, while those mated 7-10, 11-20 and 21-60 days after weaning had 78.9%, 78.9% and 78.4% FP, respectively (P<0.001). It is concluded that repeat-service in gilts/sows resulted in a 12.5% decrease in FP. Sows returning to oestrus later than 6 days after weaning had 7% lower FP than sows mated within 6 days after weaning. PMID- 20591518 TI - Dosimetric evolution of the breast electron boost target using 3D ultrasound imaging. AB - PURPOSE: To investigate the effect of treatment planning, patient setup, and interfraction motion errors on the delivered dose for external beam electron boosts for postoperative early stage breast cancer patients. METHODS AND MATERIALS: For 5 patients, 10-15 Gy was prescribed and administered via a conventionally defined electron boost treatment field - no dose distribution was calculated. Two computed tomography (CT) data sets were acquired on an average of 47 days apart. Using Monte Carlo techniques the clinically defined electron beams were reconstructed on CT1 and CT2, and a dosimetric comparison between the two data sets was made. Additionally, 3D ultrasound (US) imaging was performed to monitor interfraction motion. 3D US images were acquired concurrently with the CT images, as well as prior to each boost fraction in the treatment room. Taking into account interfraction motion, the dose to the clinical target volume (CTV) was calculated. RESULTS: Based on conventionally determined treatment fields the CT1-based CTV D95 averaged 49% (range 12-89%) of the prescribed dose. Representing setup errors, the CT2-based CTV D95 averaged 47% (range 16-91%) of the prescribed dose. Considering interfraction motion, the average radial displacement was 11 mm, and the resulting CTV D95 was further reduced in 2/5 patients. CONCLUSIONS: Poor initial coverage at the time of planning is exacerbated by breast mobility and interfraction tumour bed motion, increasing the uncertainty in the delivered dose. PMID- 20591519 TI - Running on uneven ground: leg adjustments to altered ground level. AB - In locomotion, humans have to deal with changes in ground level like pavement or stairs. When they encounter uneven ground with changes in terrain height, they reduce their angle of attack and leg stiffness on a step. This strategy was found for the single step upward movement. However, are these adjustments the result of a general strategy? In our study we focused on leg adjustments while running up and down, implying permanent adaptation to a new track level. To investigate this, we measured ten healthy participants as they ran along a runway with 10 cm increased and 10 cm lowered steps. We found that ground reaction force, leg length, leg stiffness, and angle of attack were adjusted to the direction of the vertical disturbance (up or down) but also to its length. When running upwards, leg stiffness decreased by about 20.4% on the single step and by about 9.3% on the permanently elevated track step. In addition to that - when running downwards - leg stiffness decreased in preparation for the downward step by about 18.8%. We also observed that the angle of attack diminished on elevated contact from 61 degrees to 59 degrees, and increased on lowered contact from 61 degrees to 65 degrees. The adjustment of leg stiffness seemed to be actively achieved, whereas the angle of attack appeared to be passively adjusted, consistent with a running model that includes leg retraction in late swing phase. PMID- 20591520 TI - A limit-cycle model of leg movements in cross-country skiing and its adjustments with fatigue. AB - Using dynamical modeling tools, the aim of the study was to establish a minimal model reproducing leg movements in cross-country skiing, and to evaluate the eventual adjustments of this model with fatigue. The participants (N=8) skied on a treadmill at 90% of their maximal oxygen consumption, up to exhaustion, using the diagonal stride technique. Qualitative analysis of leg kinematics portrayed in phase planes, Hooke planes, and velocity profiles suggested the inclusion in the model of a linear stiffness and an asymmetric van der Pol-type nonlinear damping. Quantitative analysis revealed that this model reproduced the observed kinematics patterns of the leg with adequacy, accounting for 87% of the variance. A rising influence of the stiffness term and a dropping influence of the damping terms were also evidenced with fatigue. The meaning of these changes was discussed in the framework of motor control. PMID- 20591521 TI - Characterization of glucan-producing Leuconostoc strains isolated from sourdough. AB - Sourdough was previously demonstrated to be a fruitful biotope for isolation of lactic acid bacteria producing exopolysaccharides and more accurately diverse glycan polymers which have interesting applications as texturing agents or prebiotics. Characterization of polymers by (1)H and (13)C NMR spectroscopy analysis demonstrated that these strains could synthesize glucans of high structural variety and containing different amounts of alpha-(1->2), alpha-(1->3) and alpha-(1->6) linkages. In this study, fifteen glucan-producing Leuconostoc mesenteroides and L. citreum strains from sourdoughs were characterized according to carbohydrate fermentation, rep-PCR fingerprinting using (GTG)(5) primers and glycansucrase activity (soluble or cell-associated). Enzyme characterization using SDS-PAGE and in situ polymer production after incubation with sucrose correlated with synthesis of classical or alpha-(1->2) branched dextrans, alternan and levan. In addition, the presence of genes coding for alternansucrase was detected by PCR and partially characterized by sequence analysis. We thus provide new information on the biodiversity of glucan production by sourdough Leuconostoc strains. PMID- 20591522 TI - Increased levels of 8-hydroxydeoxyguanosine in the vitreous of patients with diabetic retinopathy. AB - We determined the intravitreous level of 8-hydroxydeoxyguanosine (8-OHdG) in diabetic retinopathy (DR) and analyzed the relation between oxidative stress and DR. Vitreous 8-OHdG concentration increased significantly in 18 patients (20 eyes) with DR compared with controls with macular disease. This result suggests that increased oxidative stress is involved in DR. PMID- 20591523 TI - Comparison of agouti-related peptide levels in peripheral blood of postpartum pre eclamptic and non pre-eclamptic women and in umbilical cord blood from their pregnancies. AB - Plasma levels of agouti-related peptide (AgRP) were reported to continuously rise during ongoing pregnancy in rats. The aim of the study was to investigate the maternal pre-partum peripheral plasma levels of AgRP and levels in umbilical cord blood in pre-eclamptic and physiological pregnancies in humans. PMID- 20591524 TI - Association between the -634C/G polymorphisms of the vascular endothelial growth factor and retinopathy in type 2 diabetes: a meta-analysis. AB - AIMS: To investigate the association of vascular endothelial growth factor (VEGF) -634C/G polymorphism with retinopathy in type 2 diabetes. METHODS: 8 studies with 1183 cases and 1057 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. RESULTS: Our meta-analysis did not suggest a significant association of the -634C/G polymorphism with diabetic retinopathy (DR) and proliferative diabetic retinopathy (PDR) (P>0.05). The pooled odds ratios (ORs) for allelic frequency comparison, recessive model comparison, dominant model comparison, and additive model showed that the -634C/G polymorphism is significantly associated with nonproliferative diabetic retinopathy (NPDR): OR=1.61 [95% confidence interval (CI, 1.23, 2.10)], P=0.0005, P(heterogeneity)=0.38, OR=2.24 [95% CI (1.15, 4.39)], P=0.02, P(heterogeneity)=0.24, OR=1.87 [95% CI (1.01, 3.48)], P=0.05, P(heterogeneity)=0.16, and OR=2.91 [95% CI (1.33, 6.39)], P=0.008, P(heterogeneity)=0.26, respectively. However, in sensitivity analyses, we only detected a marginally significant association of the C allele with NPDR: OR=1.54 [95% CI (1.00, 2.39)], P=0.05, P(heterogeneity)=0.17. CONCLUSIONS: Our meta analysis does not support the association of the VEGF -634C/G polymorphism with DR and PDR. Significant association between this polymorphism and NPDR was detected in this meta-analysis. However, this association is not robust and could be due to chance. PMID- 20591525 TI - Clinical and genetic analysis of the insulin receptor gene in a Chinese patient with extreme insulin resistance. AB - Several types of mutations in insulin receptor gene have been identified in patients with type A insulin resistance. A 21-year old girl was diagnosed with diabetic retinopathy and cataract after 6 years of uncontrolled diabetes. Three nucleotide substitution mutations were detected, which may be associated with the patient's extreme insulin resistance. PMID- 20591526 TI - Diabetes research and clinical practice. PMID- 20591527 TI - Angiotensin converting enzyme inhibitor or angiotensin II receptor blocker for the prevention of type 2 diabetes mellitus? PMID- 20591528 TI - Factors determining successful engraftment of hepatocytes and susceptibility to hepatitis B and C virus infection in uPA-SCID mice. AB - BACKGROUND & AIMS: The human liver-uPA(+/+)-SCID mouse is currently the best small animal model available for viral hepatitis infection studies. METHODS: We identify critical factors affecting animal survival, engraftment efficacy, kinetics of liver repopulation and virological outcome by analysing the data from 400 human hepatocyte transplantations and 115 subsequent HBV and/or HCV inoculations in this mouse model. RESULTS: Almost one third of animals succumbed during the first week after hepatocyte transplantation. Only during this critical period, liver necrosis due to embolization of donor cells in the portal vein was observed. This may have caused a fatal acute liver failure that complicated the pre-existing chronic liver disease. From the second week onwards, confluent hepatocyte clusters repopulated the liver and restored its synthetic functions as evidenced by increasing human albumin levels in plasma. Xenogenic repopulation by human cells proceeded approximately 4-times slower compared to allogenic mouse hepatocytes. All HBV inoculations were successful, even in animals with low graft take. HCV infection rate varied substantially, although every donor cell type yielded infectable animals. A reproducible 100% HCV infectivity was reached with high quality inocula in animals with human albumin plasma levels >1 mg/ml. Superior animal survival, adequate liver engraftment and a high viral infection rate were observed after transplanting cryopreserved commercial human hepatocytes. CONCLUSIONS: Our findings favour the use of commercially available, cryopreserved human hepatocytes for the humanization of the uPA(+/+)-SCID liver. While HBV infectivity criteria are less stringent, human albumin plasma levels exceeding 1 mg/ml are required for a consistent HCV infection in chimeric mice. PMID- 20591529 TI - Sibling caregiving among children orphaned by AIDS: synthesis of recent studies for policy implications. AB - OBJECTIVE: The HIV/AIDS epidemic has increased the number of orphans who have to care for their younger siblings. However, their caregiving practices are poorly reported. This review aimed to explore and accumulate available evidences on sibling caregiving among children orphaned by AIDS. METHODS: We conducted a systematic review of sibling caregiving among AIDS orphans in developing countries and identified 25 relevant articles. We analysed the compiled literature and extracted information on the prevalence of sibling caregiving, the framework of sibling caregiving, factors influencing caregiving, and the impact of sibling caregiving on caregivers and those cared for. RESULTS: Sibling caregiving, which includes economic, physical, psychological, and educational care, was influenced by children's, familial, community, and policy factors. Unlike sibling caregiving that occurs under adequate adult supervision, sibling caregiving among AIDS orphans negatively impacts both the sibling caregivers and the cared for. However, the lack of studies about such sibling caregiving had prevented measurement of the level of burden and impact of sibling caregiving on orphans. CONCLUSIONS: Policy makers need to be aware that older children caring for younger siblings risk physical and psychological ill health and information must be collected so that measures can be developed to mitigate this burden on orphans. PMID- 20591530 TI - Repeats, longevity and the sources of mtDNA deletions: evidence from 'deletional spectra'. AB - Perfect direct repeats and, in particular, the prominent 13 bp repeat, are thought to cause mitochondrial DNA (mtDNA) deletions, which have been associated with the aging process. Accordingly, individuals lacking the 13 bp repeat are highly prevalent among centenarians and overall number of perfect repeats in mammalian mitochondrial genomes negatively correlates with species' longevity. However, detailed examination of the distribution of mtDNA deletions challenges a special role of the 13 bp repeat in generating mtDNA deletions. Instead, deletions appear to depend on long and stable, albeit imperfect, duplexes between distant mtDNA segments. Furthermore, significant dissimilarities in breakpoint distributions suggest that multiple mechanisms are involved in creating mtDNA deletions. PMID- 20591531 TI - Recruiting future talent in ecology and evolutionary biology. PMID- 20591532 TI - Promiscuous DNA: horizontal transfer of transposable elements and why it matters for eukaryotic evolution. AB - Horizontal transfer is the passage of genetic material between genomes by means other than parent-to-offspring inheritance. Although the transfer of genes is thought to be crucial in prokaryotic evolution, few instances of horizontal gene transfer have been reported in multicellular eukaryotes; instead, most cases involve transposable elements. With over 200 cases now documented, it is possible to assess the importance of horizontal transfer for the evolution of transposable elements and their host genomes. We review criteria for detecting horizontal transfers and examine recent examples of the phenomenon, shedding light on its mechanistic underpinnings, including the role of host-parasite interactions. We argue that the introduction of transposable elements by horizontal transfer in eukaryotic genomes has been a major force propelling genomic variation and biological innovation. PMID- 20591534 TI - Analysis of phosphorus-deficient responsive miRNAs and cis-elements from soybean (Glycine max L.). AB - Phosphorus is one of the major factors controlling plant growth and productivity. Although physiological and molecular processes of P deficiency have been intensively investigated, our current understanding of the coordinated regulation of phosphate-responsive genes and signal networks is limited. In the present study, we performed a microarray-based genome-wide transcriptional analysis of miRNAs from soybean (Glycine max L.) under phosphate deficiency. miRNAs extracted from P-deficient and P-sufficient soybean were hybridized to an array containing 853 known plant miRNA sequences. An induction ratio significant at p<0.01 was observed for 57 miRNAs belonging to 27 families. Among these miRNA families, which differentially expressed, 7 and 8 were found to be up-regulated, whereas 17 and 6 were down-regulated in leaves and roots, respectively. Seven representative individual miRNAs were selected for qRT-PCR validation, and most showed an expression pattern similar to that on microarray. We further predicted P responsive cis-elements from the promoters of miRNAs in response to and non responding to P deficiency. In total, 125 putative cis-elements were identified for 24 soybean P-deficient responsive miRNAs. Interestingly, those miRNAs (54) not responding to P deficiency were also found to contain the same P-responsive motifs. A comparative analysis revealed that the frequency of the motif occurrence in the promoters of miRNA genes in response to P deficiency was higher than that of miRNA genes not responding to P deficiency. Our study provides initial evidence in soybean that a set of miRNAs with a high frequency of P responsive cis-elements may coordinately regulate the plant response to P deficiency. PMID- 20591533 TI - Structural and functional characterization of a human IgG monoclonal antiphospholipid antibody. AB - Antiphospholipid antibodies (aPL) are likely involved in the pathogenesis of the antiphospholipid syndrome (APS). This study analyzes the structural and functional characteristics of a human monoclonal aPL (HL7G) from the IgG2 subtype with lambda light chains generated from a patient with primary APS and recurrent cerebral microemboli. DNA encoding the variable region of heavy and light chains of the antibody was sequenced, analyzed, and compared to HL5B a previously described monoclonal aPL from the same patient. Both antibodies are derived from the same germline genes. HL7G had similar but more extensive somatic mutations in the CDR1 and 2 regions than HL5B, indicating that both antibodies are closely related and derived by a T cell-dependent antigen driven process. In ELISA assays HL7G bound to cardiolipin and several other phospholipid antigens in the absence of protein cofactors. Different from HL5B this aPL bound to beta2-glycoprotein I (beta2GPII). This suggests that reactivity of aPL against beta2GPI is determined by only few specific amino acid exchanges. HL7G was able to induce tissue factor (TF) as one of the procoagulant effects of aPL. Our data suggest that the binding specificity of aPL is only of limited value to predict the biological effect and the pathophysiological impact of the antibodies. PMID- 20591535 TI - Awareness of government seasonal and 2009 H1N1 influenza vaccination recommendations among targeted US adults: the role of provider interactions. AB - We present nationally representative estimates regarding awareness of government vaccination recommendations for seasonal and 2009 H1N1 influenza among US adults for whom such vaccinations are specifically recommended. We also show how awareness varies based on interactions with health care providers. Despite comprehensive media coverage of the H1N1 pandemic, awareness of government influenza vaccination recommendations among adults is low. Provider-based vaccination counseling may help increase adults' awareness of federal vaccination recommendations. PMID- 20591536 TI - [Hand phaeohyphomycosis in a kidney transplant patient]. PMID- 20591537 TI - Synthesis and cytotoxic activities of group 3 metal complexes having monoanionic tridentate ligands. AB - Complexes of scandium, yttrium, samarium and neodymium bearing monoanionic tridentate ancillary ligands have been synthesized and characterized. The cytotoxic activities of novel compounds, as well as that of similar compounds previously reported have been evaluated on rat glioma (C6), murine fibrosarcoma (WHEI-164) and human embryonic kidney (HEK-293) cell lines. Scandium complex with quinolinephenoxyamine (NNHO) ligand showed very interesting activity against C6 cell line. PMID- 20591538 TI - A study of cytotoxicity of novel chlorokojic acid derivatives with their antimicrobial and antiviral activities. AB - A series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antimicrobial and antiviral activities. Mannich base derivatives were prepared through the reaction of substituted piperazine or piperidine derivatives on chlorokojic acid and formaline. The structures of the synthesized compounds were confirmed by IR, (1)H and (13)C NMR, ESI-MS, and elemental analysis. According to the activity studies, compounds 2-7 (MIC: 1-2 microg/mL) were found to be highly active against Bacillus subtilis and Staphylococcus aureus, while compounds 3, 5 and 6 showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Also, compounds 2-7 were more remarkably active against Candida albicans and Candida parapsilosis (MIC: 4-8 microg/mL). Additionally, compound 2 was the most active one against RNA virus PI-3. PMID- 20591539 TI - Pharmacophores modeling in terms of prediction of theoretical physico-chemical properties and verification by experimental correlations of novel coumarin derivatives produced via Betti's protocol. AB - A general, simple and straight forward approach to new substituted coumarin derivatives via Betti's condensation reaction of aromatic aldehydes, coumarin and ammonia precursors has been demonstrated successfully under mild reaction conditions. All the synthesized molecules were characterized on the basis of IR, (1)H NMR, (13)C NMR, Mass spectrometry and Elemental data. We have reported the design and calculated molecular properties of some coumarin derivatives on the basis of hypothetical antibacterial pharmacophores, structures which were designed to interact with both of gram positive and gram negative bacteria. A correlation of structure and activities relationship of these compounds with respect to molecular modeling, Lipinski rule of five, drug likeness, toxicity profiles and other physico-chemical properties of drugs are described and verified experimentally. PMID- 20591540 TI - [Thyroid metastasis of kidney cancer]. AB - Thyroid metastasis of solid tumors is rare and often asymptomatic. Differential diagnosis with malignant thyroid tumor is difficult. We report a 65-year-old man who presented with a solitary intrathoracic thyroid nodule of the left lobe, inaccessible to fine needle biopsy. His past medical history was remarkable for a nephrectomy for a kidney clear cell carcinoma one year before. The PET-scan did not show any abnormal fixation. A left lobo-isthmectomy was performed. Histologic examination revealed an intrathyroid metastasis of kidney carcinoma. PMID- 20591541 TI - The practical skills of newly qualified nurses. AB - This paper reports the findings from a study of newly qualified nurses and which subjects the nurses regarded as the most important in order to be able to live up to the requirements of clinical practice, and how they experience their potential for developing practical and moral skills, after the decrease in practical training. A qualitative approach guided the research process and the analysis of the data. The data was collected by participant observation and qualitative interviews with four nurses as informants. The conclusions made in this study are based on the statements and the observations of the newly qualified nurses. Our findings are discussed in relation to the Aristotelian concept and other relevant literature. The main message is that the newly qualified nurses did not feel equipped when they finished their training. This could be interpreted as a direct consequence of the decrease in practical training. Our study also underlines that the way nursing theory is perceived and taught is problematic. The interviews revealed that the nurses think that nursing theories should be applied directly in practice. This misunderstanding is probably also applicable to the teachers of the theories. PMID- 20591542 TI - Preoperative and postoperative agreement in fat free mass (FFM) between bioelectrical impedance spectroscopy (BIS) and dual-energy X-ray absorptiometry (DXA) in patients undergoing cardiac surgery. AB - BACKGROUND & AIMS: To measure undernutrition in terms of fat free mass (FFM), there are several options. The aim of this study was to assess agreement in FFM between the portable, bedside bioelectrical impedance spectrometry (BIS) and relatively expensive, non-portable dual-energy X-ray absorptiometry (DXA) in patients undergoing cardiac surgery. METHODS: In a prospective study, body composition measurements by BIS and DXA were performed two weeks prior and two months after cardiac surgery. Preoperative and postoperative agreement in FFM between BIS and DXA were analyzed with Bland and Altman plots. RESULTS: Twenty six patients were analyzed. BIS overestimated preoperative and postoperative FFM by 2 kg compared to DXA (2.3 kg (95%CI: -3.5-8.1 kg) and 2.1 kg (95%CI: -4.5-8.7 kg), respectively). BIS underestimated FFM change by -0.5% (95%CI: -8.4-7.5%). CONCLUSIONS: There is a large inter-individual variation between BIS and DXA. This hinders the interchange-ability of BIS and DXA in routine clinical practice and may lead to misclassifications and thereby inappropriate nutritional treatment and possible postoperative complications. To evaluate nutritional therapy in patients undergoing cardiac surgery, we advocate the use of DXA assessed FFM in parallel to BIS assessed extracellular and intracellular water and FFM. PMID- 20591544 TI - Genetic unexceptionalism: clinician accounts of genetic testing for familial hypercholesterolaemia. AB - This paper considers the implications of genetic testing in the case of familial hypercholesterolaemia, drawing on twenty semi-structured interviews with general practitioners (family doctors in primary care), nurses and specialists in hospital clinics (secondary care) in the UK. Though these professionals appear aware of and interested in the genetic component of the condition, and DNA testing is underway in at least some centres, their accounts suggest that the genetic test is not having a major impact on clinical work. Instead we find that professionals report that they generally rely on other information when making a diagnosis, especially cholesterol levels understood as a key risk factor, while the results of DNA tests, if used, come late in a much longer series of clinical investigations, judgements and interventions. In addition to elaborating professional views of genetic testing, the research provides a way of understanding other studies that describe lay people as not necessarily privileging genetic explanations of familial hypercholesterolaemia. PMID- 20591543 TI - Characterization of the HPV-specific memory B cell and systemic antibody responses in women receiving an unadjuvanted HPV16 L1 VLP vaccine. AB - Human papillomavirus (HPV)-specific antibodies are proposed to be the correlate of protection afforded by HPV L1 virus-like particle (VLP) vaccines. Previous studies have characterized the systemic antibody response to immunization in terms of both the quantity and the ability to neutralize HPV. Here, we have adapted a generalized memory B cell ELISPOT to the HPV16 system and expanded the analysis of the systemic antibody response to include an avidity measurement of HPV L1 VLP-specific antibodies. We show the results of the memory B cell ELISPOT significantly correlated with IgG and neutralizing antibody titers, but not with the avidity measurement. This is the first comprehensive study to correlate a variety of humoral aspects potentially associated with protective immunity following vaccination with a HPV16 L1 VLP vaccine. PMID- 20591545 TI - Childhood nutritional deprivation and cognitive impairment among older Chinese people. AB - Late-life cognitive impairment may have its origins in childhood. Here, we examine the associations between markers of childhood nutritional deprivation and cognitive impairment in older adults. We made use of the 2002 and 2005 waves of the Chinese Longitudinal Healthy Longevity Survey to examine these associations for persons aged 65-105 (N=15,444). Anthropometric measures (arm length, knee height) and self-reported hunger were used to measure early-life nutritional deficiencies. Cognitive impairment was measured using the Chinese version of the Mini Mental State Examination. Results from multivariate logistic regression models show that both anthropometric measures and self-report markers of early life nutritional status were significantly associated with the odds of cognitive impairment at baseline for both men and women after controlling for age and ethnicity. Adjustments for childhood and adulthood socioeconomic status, adulthood health, and lifestyle habits had little effect on these associations except for the effect of hunger among men. Results from multinomial logistic regression models show that during the three-year follow-up period, arm length was significantly associated with the onset of cognitive impairment after controlling for various confounders in men, but not in women. Our findings suggest that early-life nutritional deprivation may contribute to cognitive impairment among older Chinese adults. PMID- 20591546 TI - Exploring children's stigmatisation of AIDS-affected children in Zimbabwe through drawings and stories. AB - AIDS-related stigma is a major contributor to the health and psychosocial well being of children affected by AIDS. Whilst it is often suggested that AIDS affected children may be stigmatised by other children, to date no research focuses specifically on child-on-child stigma. Using social representations theory, we explore how Zimbabwean children represent AIDS-affected peers, examining (i) whether or not they stigmatise, (ii) the forms stigma takes, and (iii) the existence of non-stigmatising representations that might serve as resources for stigma-reduction interventions. Our interest in identifying both stigmatising and non-stigmatising representations is informed by a theory of change which accords a central role to community-level debate and dialogue in challenging and reframing stigmatising representations. In late 2008, 50 children (aged 10-12) were asked to "draw a picture of a child whose family has been affected by AIDS in any way", and to write short stories about their drawings. Thematic analysis of stories and drawings revealed frequent references to stigmatisation of AIDS-affected children--with other children refusing to play with them, generally keeping their distance and bullying them. However children also frequently showed a degree of empathy and respect for AIDS-affected children's caring roles and for their love and concern for their AIDS-infected parents. We argue that a key strategy for stigma-reduction interventions is to open up social spaces in which group members (in this case children) can identify the diverse and contradictory ways they view a stigmatised out-group, providing opportunities for them to exercise agency in collectively challenging and renegotiating negative representations. Contrary to the common view that drawings enable children to achieve greater emotional expression than written stories, our children's drawings tended to be comparatively stereotypical and normative. It was in written stories that children most eloquently expressed meanings and emotions, and an awareness of the complexity of the scenarios they portrayed. PMID- 20591547 TI - AIDS in the family and community: the impact on child health in Malawi. AB - Pediatric HIV infections jeopardize children's health and survival. Much less is known about how the experiences of being orphaned, living with chronically ill parents, or living in a severely affected community impact child health. Our study responds by examining which HIV/AIDS-related experiences place children at greatest risk for poor health. Data from the 2004-2005 Malawi Integrated Household Survey were analyzed using logistic multilevel modeling to examine whether HIV/AIDS-related experiences within the family and community predicted reported health status among children age 6-17 years. We found higher burdens of acute and chronic morbidity for children whose parents have an AIDS-related illness. No other AIDS-related exposure, including orphanhood and recent household deaths, demonstrated a clear relationship with health status. Children living with sick parents may be at increased risk due to the spread of infectious disease and receiving limited adult care. Community home-based care programs are best situated to identify children in these difficult circumstances and to mitigate their disadvantage. PMID- 20591548 TI - Corticosteroid administration in oral and orthognathic surgery: a systematic review of the literature and meta-analysis. AB - PURPOSE: This study evaluated the effect of corticosteroid (CS) administration on edema, analgesia, and neuroregeneration in conjunction with surgical dental extraction, orthognathic surgery, and the risk of developing side effects. MATERIALS AND METHODS: A systematic search of the literature was made. The primary predictor variable was CS administration and the outcome variables were edema, pain, and infection. A meta-analysis was performed. The risk of other side effects was evaluated through a simple review. RESULTS: In oral surgery, most clinical trials showed a significant decrease in edema (P < .0001) after CS, and local injection of methylprednisolone > or =25 mg was expected to result in a significant decrease in edema. Regarding the analgesic effect, several clinical trials showed a decrease in pain after CS (P < .0001). Further, CS administration resulted in a slightly higher risk of infection (relative risk, 1.0041), but with a P value of .89. CS could be administered with no increased risk of infection. In orthognathic surgery, methylprednisolone > or =85 mg administered intravenously seemed sufficient to produce a significant decrease in edema, and several trials pointed toward a neuroregeneration effect, but no statistical analysis could be performed. Regarding the risk of other side effects, in oral surgery, a minimal risk of chronic adrenal suppression was seen; in orthognathic surgery, an elevated risk of avascular osteonecrosis, steroid-induced psychosis, and adrenal suppression was seen. There were no reports of decreased healing. CONCLUSION: These findings suggest that the administration of CS in oral surgery decreases edema and pain significantly, with no higher risk of infection and with a minimum risk of other side effects. PMID- 20591549 TI - Endoscopic approach to removal of an osteochondroma of the mandibular condyle. PMID- 20591550 TI - Microvascular free bone flap harvest with piezosurgery. PMID- 20591551 TI - The fibula osteomyocutaneous flap for mandible reconstruction: a 15-year experience. AB - PURPOSE: This report documents our experience over the previous 15 years using free vascularized fibular flaps for comprehensive reconstruction of large defects in the mandible, after combined resections of aggressive, malignant odontogenic tumors or for post-traumatic defects. PATIENTS AND METHODS: Charts were reviewed retrospectively for 117 consecutive patients who underwent microsurgical reconstruction of the oromandibular complex with a fibula osteocutaneous or osteomyocutaneous free flap over a 15-year period, with an average follow-up of 4 years. All charts were reviewed retrospectively for tumor type, stage and location, surgical procedure performed (including type of plate used), dental restoration if done, the use of pre- or postoperative radiotherapy, length of follow-up, and evidence of complications. RESULTS: Fibula osteocutaneous free flaps were used for reconstruction in 117 patients, of whom 60% were men (mean age, 57.1 years) and 40% were women (mean age, 56.6 years). Most cases (61.1%) were secondary to oral malignancies (89.1% of these were squamous cell carcinoma). Thirty-one patients (26.5%) developed postoperative complications, including hardware failure or intolerance in 16 patients (13.7%), total or partial flap failure in 10 patients (8.5%), wound infection in 3 patients (2.6%), and peroneal nerve damage in 2 patients (1.7%). Regarding donor site morbidity, calf paresthesias were recorded in 21% of cases. Similar rates of claw-toe deformity were also observed. CONCLUSIONS: In our opinion, the free fibula osteocutaneous flap is the most versatile and reliable option for microsurgical reconstruction of large mandibular defects. It provides a large quantity of bone, which is easily shaped to passively adapt to the remaining mandible. The bone height is suitable for an implant-based prosthetic restoration. Preoperative mapping of the cutaneous perforators of the skin paddle improves the versatility of the flap design and decreases the morbidity at the donor site. In selected cases, other options (iliac crest or scapular free flap) may also be considered. PMID- 20591552 TI - Partial laryngospasms during general anesthesia with a laryngeal mask airway for dental treatment: a report of 5 cases. PMID- 20591554 TI - Intraoral diffuse large B-cell lymphoma with Burkitt-like morphology in an HIV positive patient--a diagnostic dilemma. PMID- 20591553 TI - Comparison of actual surgical outcomes and 3-dimensional surgical simulations. AB - PURPOSE: The advent of imaging software programs has proved to be useful for diagnosis, treatment planning, and outcome measurement, but precision of 3 dimensional (3D) surgical simulation still needs to be tested. This study was conducted to determine whether the virtual surgery performed on 3D models constructed from cone-beam computed tomography (CBCT) can correctly simulate the actual surgical outcome and to validate the ability of this emerging technology to recreate the orthognathic surgery hard tissue movements in 3 translational and 3 rotational planes of space. MATERIALS AND METHODS: Construction of pre- and postsurgery 3D models from CBCTs of 14 patients who had combined maxillary advancement and mandibular setback surgery and 6 patients who had 1-piece maxillary advancement surgery was performed. The postsurgery and virtually simulated surgery 3D models were registered at the cranial base to quantify differences between simulated and actual surgery models. Hotelling t tests were used to assess the differences between simulated and actual surgical outcomes. RESULTS: For all anatomic regions of interest, there was no statistically significant difference between the simulated and the actual surgical models. The right lateral ramus was the only region that showed a statistically significant, but small difference when comparing 2- and 1-jaw surgeries. CONCLUSIONS: Virtual surgical methods were reliably reproduced. Oral surgery residents could benefit from virtual surgical training. Computer simulation has the potential to increase predictability in the operating room. PMID- 20591555 TI - A simple and flexible concept for computer-navigated surgery of the mandible. PMID- 20591556 TI - Multiple superficial mucoceles on lower lip, soft palate, retromolar region, and floor of mouth. PMID- 20591557 TI - Modulation of endocrine and transport functions in human trophoblasts by saquinavir and nelfinavir. AB - OBJECTIVES: The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus. STUDY DESIGN: The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality. RESULTS: Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1. CONCLUSION: These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions. PMID- 20591559 TI - Catastrophic flood and forest cover change in the Huong river basin, central Viet Nam: a gap between common perceptions and facts. AB - Recent catastrophic floods in Viet Nam have been increasingly linked to land use and forest cover change in the uplands. Despite the doubts that many scientists have expressed on such nexus, this common view prompted both positive forest protection/reforestation programs and often-unwarranted blame on upland communities for their forest management practices. This study discusses the disparity between public perceptions and scientific evidences relating the causes of catastrophic floods. The former was drawn on the results of a questionnaire and focus groups discussions with key informants of different mountainous communities, whereas the latter was based on GIS and remote sensing analysis of land cover change, including a statistical analysis of hydro-meteorological data of the Huong river basin in Viet Nam. Results indicate that there is a gap between the common beliefs and the actual relationship between the forest cover change and catastrophic floods. Undeniably, the studied areas showed significant changes in land cover over the period 1989-2008, yet, 71% of the variance of catastrophic flood level in the downstream areas appeared related to variance in rainfall. Evidences from this study showed that the overall increasing trends of catastrophic flooding in the Huong river basin was mainly due to climate variability and to the development of main roads and dyke infrastructures in the lowlands. Forest management policies and programs, shaped on the common assumption that forest degradation in the upland is the main cause of catastrophic flood in the downstream areas, should be reassessed to avoid unnecessary strain on upland people. PMID- 20591560 TI - Unilateral rhythmic testicular movements. AB - A male patient came to our clinic because of a continuous up and down movement of his right testis, which was present even during sleep. The nature and localization of the unilateral rhythmic cremasteric activity is investigated by electrophysiological methods. Investigations of the cremasteric muscles and genitofemoral nerve determined that the movement was similar to myokymia. The localization of this peculiar spontaneous movement is probably in motor fibers somewhere between the L1-L2 motor neuron pool, motor roots and/or the genitofemoral nerve. PMID- 20591561 TI - Diffusion experiments for estimating radiocesium and radiostrontium sorption in unsaturated soils from Spain: comparison with batch sorption data. AB - As sorption data obtained from batch tests are often used to estimate pollutant transport in unsaturated soils, comparison between sorption data obtained in the two conditions is required to ensure a correct risk assessment. With this aim, radiostrontium and radiocesium apparent diffusion coefficients (D(a)) were quantified in nine unsaturated soils, and the derived distribution coefficients (K(d)) were compared with K(d) data from batch experiments. The D(a)(Sr) and the D(a)(Cs) ranged from 1.8x10(-11) to 1.5x10(-10) m(2) s(-1), and from 1.0x10(-13) to 5.9x10(-11) m(2) s(-1), respectively. The D(a)(Sr) varied according to both soil packing parameters and properties governing Sr interaction. For Cs, the soil sorption properties explained the variation on D(a)(Cs). The K(d) values derived from D(a) (from 0.014 to 1.8 L kg(-1) for Sr; from 0.55 to 942 L kg(-1) for Cs) were lower than from batch tests (from 1 to 97 L kg(-1) for Sr; from 10 to 14,600 L kg(-1) for Cs), thus indicating that batch data may not accurately describe radionuclide transport in unsaturated soils. However, the two sets of data correlated well, thus suggesting that radionuclide transport can be estimated from batch tests, which are faster than diffusion experiments. PMID- 20591562 TI - The 2007 water crisis in Wuxi, China: analysis of the origin. AB - An odorous tap water crisis that affected two million residents for several days occurred in Wuxi, China in the summer of 2007. Volatile sulfide chemicals including methyl thiols, dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide were the dominant odorous contaminants in Lake Taihu and in tap water during the crisis. These contaminants originated from the decomposition of a massive cyanobacterial bloom that was triggered by illegal industrial discharges and inadequately regulated domestic pollution. A specific emergency drinking water treatment process was quickly developed using a combination of potassium permanganate oxidation and powdered activated carbon adsorption. The emergency treatment process removed the odor from the tap water and solved the crisis successfully in several days. This experience underscores the suggestion that a combination of stresses associated with eutrophication and industrial and domestic wastewater discharges can push an aquatic system to the tipping point with consequences far more severe than would occur if the system were subjected to each stress separately. PMID- 20591563 TI - Synthesis and photocatalytic activity of N-doped NaTaO3 compounds calcined at low temperature. AB - N-doped NaTaO(3) compounds (NaTaO(3-x)N(x)) were successfully synthesized using NaTaO(3) prepared at low calcination temperature as starting material and melamine (C(3)H(6)N(6)) as nitrogen source. The as-prepared NaTaO(3-x)N(x) samples were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and UV-vis diffuse reflectance spectra. The XRD results indicate that the crystallization temperature of NaTaO(3) is up to 700 degrees C and the doping of N does not lead to significant structural changes. Moreover, as observed by SEM images, the particle sizes of resultant NaTaO(3-x)N(x) are in the range of 100-150 nm, which are much smaller than NaTaO(3) particles synthesized by traditional solid state reaction method. The photocatalytic activities of NaTaO(3-x)N(x) were examined by methylene blue (MB) aqueous solution under UV light. It is found that the photocatalytic activity of NaTaO(3-x)N(x) depend strongly on the doping content of N, and sample NaTaO(2.961)N(0.039) shows the highest photocatalytic activity for the degradation of MB. Furthermore, it is also found that NaTaO(3-x)N(x) catalysts display super structural stabilities during photocatalytic degradation, and could recover their photocatalytic activity after calcination at 500 degrees C, suggesting a promising utilization of such photocatalyst. PMID- 20591564 TI - Disinfection and solubilization of sewage sludge using the microwave enhanced advanced oxidation process. AB - The microwave enhanced advanced oxidation process (MW/H(2)O(2)-AOP) was used to treat municipal sewage sludge for solids disintegration, nutrient solubilization, with an emphasis on pathogen destruction and regrowth. Pathogen reduction, in terms of fecal coliform concentrations were found below detection limit (1000 CFU/L) immediately after treatment when sludge was treated at 70 degrees C with more than 0.04% of H(2)O(2) (w/w). Significant regrowth of fecal coliforms was observed for the treated samples after 72 h. However, no regrowth was observed for samples treated at 70 degrees C with 0.08% H(2)O(2) or higher, suggesting a complete elimination of fecal coliforms. The range of hydrogen peroxide used did not have a significant effect on orthophosphate release regardless of temperature. Ammonia release at these low temperatures was found to be insignificant. The soluble chemical oxygen demand increased with an increase of hydrogen peroxide dosage at 70 degrees C. However, there was no clear trend of soluble chemical oxygen demand over varying hydrogen peroxide dosage at 55 degrees C. The MW/H(2)O(2)-AOP is a novel process for the pasteurization and stabilization of sewage sludge to meet and maintain Class A biosolids criteria. PMID- 20591565 TI - Exploring the ability of Sphingobacterium sp. ATM to degrade textile dye Direct Blue GLL, mixture of dyes and textile effluent and production of polyhydroxyhexadecanoic acid using waste biomass generated after dye degradation. AB - The degradation of textile effluent using microorganisms has been studied extensively, but disposal of generated biomass after dye degradation is a serious problem. Among all tested microorganisms, isolated Sphingobacterium sp. ATM effectively decolorized (100%) the dye Direct Blue GLL (DBGLL) and simultaneously it produced (64%) polyhydroxyhexadecanoic acid (PHD). The organism decolorized DBGLL at 300 mg l(-1) concentration within 24 h of dye addition and gave optimum production of PHD. The organism also decolorized three combinations of mixture of dyes. The organism decolorized textile effluent too when it was combined with medium. The organism produced a maximum of 66% and 61% PHD while decolorizing mixture of dyes and textile effluent respectively. Molasses was found to be more significant within all carbon sources used. The activity of polyhydroxyalkanoate (PHA) synthase was found to be higher after 24 h of addition of DBGLL. The enzymes responsible for dye degradation, viz. veratryl alcohol oxidase, laccase, DCIP (2,6-dichlorophenol-indophenol) reductase, riboflavin reductase, and azo reductase were found to be induced during decolorization process of DBGLL and mixture of dyes. There was significant reduction in chemical oxygen demand (COD) and biological oxygen demand (BOD). FTIR analysis of samples before and after decolorization of dye confirmed the biotransformation of DBGLL. PMID- 20591566 TI - Inside the removal of lead(II) from aqueous solutions by De-Oiled Allspice Husk in batch and continuous processes. AB - A new adsorbent material for removing lead ions from aqueous solutions has been investigated. The residue of the allspice extraction process (De-Oiled Allspice Husk) was used on the removal of Pb(II) from water solutions. The lead sorption capacity of De-Olied Allspice Husk (DOAH) was studied in batch and continuous processes. It was found that percentage removals of Pb(II) depend on the pH and the initial lead concentrations. The Pb(II) uptake process was maximum at pH 5 in a range concentrations of 5-25 mg L(-1). The overall sorption process was well described by the pseudo-second-order kinetic model under conditions of pH 5 (0.1 g adsorbent per 100 mL of contaminated solution) 0.001 mass/volume ratio and 25 degrees C. The sorption capacity of lead(II) onto DOAH in batch process was 5.00, 8.02, 11.59, 15.23 and 20.07 mg g(-1), when the concentration solutions were 5, 10, 15, 20 and 25 mg L(-1) respectively. These values are lower than obtained in continuous process, where lead was removed by 95% and the experimental results were appropriately fitted by the Yoon-Nelson model. X-ray photoelectron spectroscopy (XPS) provides information regarding the interactions between lead ions and the adsorbent surface indicating that the formation of 2 complexes depends on the functional groups associated. PMID- 20591567 TI - Ignition and explosion risks of nanopowders. AB - Characterization methods with regard to nanopowder flammability and explosivity are presented and illustrated for few nanopowders. Analytical models are developed in order to explain the dependency of the combustion times on the particle diameter. Experimental evidence shows that there exists, for carbonaceous and metallic materials, mainly two combustion regimes that are either kinetically controlled, for small size particles, or diffusion controlled, for large size particles. From the experimentally measured combustion data of those materials, the dependencies of the ignition temperature and the minimal explosive concentration (MEC) with regard to the particle size have been analyzed. We found that the two combustion regimes yield two different tendencies with respect to the particle size. Overall, it is found that as the particle size decreases, minimum ignition temperature (MIT) and minimum ignition energy (MIE) decrease, indicating higher potential inflammation and explosion risks for the use of nanopowders. By contrast, the minimal explosion concentration (MEC) did not show strong variations as the particle size decreases. Rather, a theoretical plateau is observed, which was experimentally confirmed. We also observed that carbon nanopowders exhibit a low propensity to explode while metallic nanopowders can be very reactive, thus delineating high potentials for explosion risks in manufacturing facilities. PMID- 20591568 TI - Relationship between photosynthetic capacity, nitrogen assimilation and nodule metabolism in alfalfa (Medicago sativa) grown with sewage sludge. AB - Sewage sludge has been used as N fertilizer because it contains some of inorganic N, principally as nitrate and ammonium ions. However, sewage sludge addition to legumes could result in impaired nodule metabolism due to the presence of inorganic N from sludge. A greenhouse experiment was conducted to examine the effects of sewage sludge on growth, photosynthesis, nitrogen assimilation and nodule metabolism in alfalfa (Medicago sativa L. cv. Aragon). Plants were grown in pots with a mixture of perlite and vermiculite (2:1, v/v). The experiment included three treatments: (1) plants inoculated with rhizobia and amended with sewage sludge at rate of 10% (w/w) (RS); (2) plants inoculated with rhizobia without any amendment (R); and (3) non-inoculated plants fed with ammonium nitrate (N). N(2)-fixing plants had lower growth and sucrose phosphate synthase activity but higher photosynthesis than nitrate-fed plants because they compensated the carbon cost of the rhizobia. However, sewage sludge-treated plants evidenced a loss of carbon sink strength due to N(2) fixation by means of decreased photosynthetic capacity, leaf chlorophylls and N concentration in comparison to untreated plants. Sewage sludge did no affect nodulation but decreased nodule enzyme activities involved in carbon and N metabolisms that may lead to accumulation of toxic N-compounds. PMID- 20591569 TI - Kinetic degradation model and estrogenicity changes of EE2 (17alpha ethinylestradiol) in aqueous solution by UV and UV/H2O2 technology. AB - The photochemical degradation and estrogenicity removal of 17alpha ethinylestradiol in aqueous solutions was investigated via ultraviolet (UV) photolysis and UV/H(2)O(2) process with a low-pressure UV lamp. The results indicated that the kinetics of both oxidation processes well fitted the pseudo first-order kinetics. EE(2) can be partially removed by UV radiation alone with kinetic constants increasing from 0.0054 to 0.2753 min(-1) with the UV intensity increase. The EE(2) degradation rate enhanced from 0.0364 to 0.0684 min(-1) when H(2)O(2) was combined with the photolysis process (UV/H(2)O(2)), even though EE(2) was not oxidized when same amounts of H(2)O(2) existed in the aqueous solutions. The kinetic parameters of pseudo-first-order kinetics showed positive correlation to UV intensity and also H(2)O(2) concentration, however negative to the initial EE(2) concentration. A regression model was developed for pseudo first-order rate constant as a function of the UV intensity, H(2)O(2) concentration and initial EE(2) concentration, which could be used to estimate the EE(2) degradation rate at various operational conditions. The yeast estrogen screen (YES) was employed to evaluate the estrogenicity of photolytic water samples. Results showed that more than 95% of the estrogenicity was removed after 40 min irradiation and the parent compound EE(2) was mainly responsible for the observed estrogenicity. PMID- 20591570 TI - Size matters - small fiber neuropathy in the Guillain-Barre syndrome. PMID- 20591571 TI - Neurophysiological assessment of spinal cord stimulation in failed back surgery syndrome. AB - Despite good clinical results, the mechanisms of action of spinal cord stimulation (SCS) for the treatment of chronic refractory neuropathic pain have not yet been elucidated. In the present study, the effects of SCS were assessed on various neurophysiological parameters in a series of 20 patients, successfully treated by SCS for mostly unilateral, drug-resistant lower limb pain due to failed back surgery syndrome. Plantar sympathetic skin response (SSR), F-wave and somatosensory-evoked potentials (P40-SEP) to tibial nerve stimulation, H-reflex of soleus muscle, and nociceptive flexion (RIII) reflex to sural nerve stimulation were recorded at the painful lower limb. The study included two recording sets while SCS was switched 'ON' or 'OFF' for 1h. Significant changes in 'ON' condition were as follows: SSR amplitude, H-reflex threshold, and RIII reflex threshold and latency were increased, whereas SSR latency, F-wave latency, H-reflex amplitude, P40-SEP amplitude, and RIII-reflex area were reduced. Analgesia induced by SCS mainly correlated with RIII attenuation, supporting a real analgesic efficacy of the procedure. This study showed that SCS is able to inhibit both nociceptive (RIII-reflex) and non-nociceptive (P40-SEP, H-reflex) myelinated sensory afferents at segmental spinal or supraspinal level, and to increase cholinergic sympathetic skin activities (SSR facilitation). Complex modulating effects can be produced by SCS on various neural circuits, including a broad inhibition of both noxious and innocuous sensory information processing. PMID- 20591572 TI - The course of chronic and recurrent low back pain in the general population. AB - Using latent class analysis (LCA), a previous study on patients attending primary care identified four courses of low back pain (LBP) over the subsequent 6 months. To date, no studies have used longitudinal pain recordings to examine the "natural" course of recurrent and chronic LBP in a population-based sample of individuals. This study examines the course of LBP in the general population and elaborates on the stability and criterion-related validity of the clusters derived. A random sample of 400 individuals reporting LBP in a population-based study was asked to complete a comprehensive questionnaire at the start and end of the year's survey, and 52 weekly pain diaries in between. The latter were analyzed using LCA. 305 individuals returned more than 50% of the diaries. Four clusters were identified (severe persistent, moderate persistent, mild persistent, and fluctuating). The clusters differed significantly with regards to pain and disability. Assessment of cluster stability showed that a considerable proportion of patients in the "fluctuating" group changed their classification over time. Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care. Due to the population-based design, this study achieves, for the first time, a close insight into the "natural" course of chronic and recurrent low back pain, including individuals that did not necessarily visit the general practitioner. The findings will help to understand better the nature of this pain in the general population. PMID- 20591573 TI - Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study. AB - Canine vector-borne diseases (CVBDs) are highly prevalent and increasing in distribution worldwide. A longitudinal study was conducted in southern Italy to determine the incidence of and protection against CVBD-causing pathogens in dogs treated with a combination of imidacloprid 10% and permethrin 50% (ImPer). One hundred eleven autochthonous young dogs were divided into group A (n=63) and group B (n=48), both groups containing dogs positive and negative for one or more CVBD-causing pathogens. Additionally, 10 naive male beagles were introduced in each group in May 2008. Group A was treated with ImPer on day 0 and every 21+/-2 days whereas group B was left untreated. Blood and skin samples were collected at baseline (March-April 2008) and at the first, second and third follow-up times (July and October 2008 and April 2009). Bone marrow was sampled at baseline and at the third follow-up. Serological, cytological and molecular tests were performed to detect Anaplasma platys, Babesia spp., Bartonella spp., Dirofilaria immitis, Ehrlichia canis, Hepatozoon canis and Leishmania infantum. Ectoparasites (fleas, ticks, and sand flies) were monitored throughout the study. The baseline prevalence of CVBDs was 39.6% with 44 dogs positive for at least one pathogen. A. platys (27.5%) and Babesia spp. (15.6%) were the most prevalent species and co infections with up to two pathogens were detected in 16 (14.7%) individuals. At the end of the evaluation period, there was a 90.7% reduction in overall CVBD incidence density rate (IDR) in group A, as following: 100% reduction in L. infantum; 94.6% in E. canis; 94.4% in Babesia spp.; and 81.8% in A. platys. Initially positive treated dogs showed significantly lower pathogen prevalence at the third follow-up than untreated ones. At the end of the evaluation period, 8 of the 10 untreated beagles were infected with at least one pathogen whereas one of the treated beagles was A. platys positive at a single time point (second follow-up). Overall efficacy against ticks was 97.9%. In October 2009, samples were collected from the remaining 83 dogs (44 from group A and 39 from group B) to investigate the annual incidence of CVBDs in the same, at this time untreated, dog population. A high year incidence for tick-borne diseases (78.1%) and for L. infantum (13.6%) was detected in dogs from group A, seven months after the treatment had been withdrawn. The results demonstrate that ImPer preventive treatment against arthropods protects autochthonous and naive beagle dogs against CVBD-causing pathogens. PMID- 20591574 TI - Reporting and methodological quality in evidence-based medicine studies in burn surgery. PMID- 20591575 TI - 5-Azacytidine in myelodysplastic syndromes: a clinical practice guideline. AB - BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoiesis that results in peripheral blood cytopenias and a marked propensity to progress to acute myelogenous leukemia. With 40,000-76,000 new cases per year in the USA, MDS is the commonest of the hematological malignancies and represents a significant burden of morbidity and premature death. Although supportive or palliative measures such as blood transfusion have long been the mainstay of management of MDS, disease-modifying medical therapies have recently become available. The most extensively characterized of these is 5-azacytidine (5-Aza); however, no consensus exists on how this agent should be deployed in MDS. METHODS: An overarching search of the literature identified 7019 citations investigating the treatment or management of MDS. Of those, six clinical articles of prospective phase 2-3 study design or meta-analyses were selected for inclusion in a systematic review of the evidence. CONCLUSIONS: The Canadian Consortium on Evidence-Based Care in MDS recommends 5-Aza as first line therapy in all MDS patients with IPSS high-intermediate and high risk scores including WHO-defined AML (20-30% blasts) who cannot proceed immediately to allogeneic stem cell transplant. 5-Aza is not recommended as first line therapy with MDS patients with IPSS Low and Low-intermediate risk scores as there is no evidence that it alters the natural history of the disease nor is superior to standard therapy. The MDS consortium does not recommend combining 5-Aza with other agents at this time outside the context of a clinical trial. PMID- 20591576 TI - Bruising on ostrich carcasses and the implications on the microbiology and losses in utilizable meat when removing them post-evisceration or post-chilling. AB - Bruising on ostrich carcasses reduces meat yield. These bruises are usually removed as part of the primary meat inspection, performed directly after evisceration. Three separate studies were conducted to determine the advantages and disadvantages of removing the bruises at primary meat inspection or after overnight cooling of the ostrich carcasses (0-4 degrees C). The bruised areas were also investigated to determine their frequency and distribution and to establish the most obvious causes and possible preventative measures. The neck bruises represented 52.58% of all bruises; the high side railings of the transport vehicles being the most probable cause. Large and multiple bruising were probably from the trampling of birds lying down. It was established that trimming bruises on warm carcasses caused higher total aerobic viable counts on the trimmed surfaces than cold trimming. Cold trimming together with better management of trimming practices also led to a decrease in meat yield losses. PMID- 20591577 TI - Chromosome DNA imbalances in human astrocytic tumors: a comparative genomic hybridization study of 63 Chinese patients. AB - Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, -4q, -10q, +7p, and -15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients. PMID- 20591578 TI - Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma. AB - The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications. PMID- 20591579 TI - TNFRSF6B neutralization antibody inhibits proliferation and induces apoptosis in hepatocellular carcinoma cell. AB - The tumor necrosis factor receptor super-family member 6b (TNFRSF6B) is over expressed in various human cancers, but its function in hepatocellular carcinoma (HCC) remains uncertain. The aim of the study was to investigate the relationship between TNFRSF6B expression and apoptosis in HCC and the effect of anti-TNFRSF6B neutralization monoclonal antibody (McAb) on HCC cells. TNFRSF6B mRNA and protein expression were compared with apoptosis in 78 cases of HCC. Proliferation, cell cycle, apoptosis, and migration ability of liver cancer cells co-cultured with anti-TNFRSF6B McAb were also detected. TNFRSF6B mRNA and protein expression in the tumor tissues negatively correlated with apoptosis. Cell proliferation was decreased, cell cycle was arrested in G1/S-phase, apoptosis was increased, and migration ability was inhibited by anti-TNFRSF6B McAb in vitro. Anti-TNFRSF6B McAb could be useful to suppress proliferation and induce apoptosis in HCC. Thus, TNFRSF6B might be a critical, targeted therapy strategy for HCC. PMID- 20591580 TI - Apoptosis-related factors p53, bcl-2 and the defects of force transmission in dilated cardiomyopathy. AB - The etiology of heart failure in dilated cardiomyopathy involves multiple agents. The purpose of this study was to investigate the presence of apoptosis-related proteins p53, bcl-2, and the defects of force transmission in end-stage dilated cardiomyopathy. We studied myocardial samples from 20 hearts with histologic findings of dilated cardiomyopathy. Myocardial samples obtained from 10 normal hearts were used as controls. An immunohistochemical method was performed with the use of desmin, N-cadherin, p53, and bcl-2 antibodies. The expression of desmin and N-cadherin was much more pronounced in dilated cardiomyopathy, and both of them were arranged disorderly. On the other hand, increased expression of p53 is associated with progressive loss of myocytes by apoptosis in heart failure, and increased expression of bcl-2 represents a possible compensatory antiapoptotic mechanism. The increased amount and the irregular distribution of desmin and N-cadherin in dilated cardiomyopathy may compensate for the loss of cellular stability due to the loss of contractile material. These alterations contribute to the deterioration of contractile function in heart failure. Furthermore, the prevalence of an apoptotic or compensatory antiapoptotic mechanism may influence the evolution of heart failure in dilated cardiomyopathy. PMID- 20591581 TI - [Patent for medical device: from design to marketing (example of Prolift(r))]. PMID- 20591583 TI - Postural control of pre-term infants at 6 and 12 months corrected age. AB - BACKGROUND: Pre-term infants are at high risk for motor disabilities. Postural control, the basis for motor development, develops rapidly during the first year of life. An early start to extra-uterine life with an immature motor system may influence a pre-term infant's postural control. AIMS: To identify important prognostic factors and determine the difference in postural control between full term and pre-term infants. METHOD: Medical records of 93 pre-term infants with birth weight of less than 1501g (mean birth weight=1136.03+/-243.86g; mean gestational age=29.14+/-2.78 weeks) were reviewed. Data was collected from the preemie clinical follow-up program at the National Cheng Kung University, Taiwan. RESULTS: Results demonstrated that pre-term infants had poorer postural control than full-term infants both at 6 and 12 months adjusted age, and that medical complication as measured by the Neonatal Medical Index was the best predictor of postural control in pre-term infants in the first year of life. In addition, our findings confirmed that the development of postural control at 6 months adjusted age predicts the development of postural control at 12 months adjusted age after controlling for prognostic factors. CONCLUSIONS: Both biological and social environmental factors appeared to be associated with pre-term infants' postural control at 6 and 12 months adjusted age. The development of postural control at 6 months adjusted age predicted the development of postural control at 12 months adjusted age. This suggested the value of early follow-up examinations at 6 months adjusted age. PMID- 20591584 TI - Relationships between ovarian cysts and morphological and hormonal state of ovarian cortex in sows. AB - The aim of this study was to evaluate the relationship between ovarian cysts and concentrations of ovarian steroid hormones: 17beta-estradiol (E(2)), progesterone (P(4)), testosterone (T), and androstendione (A(4)) both in blood plasma and in cysts and morphological state of the ovarian cortex in sows. Females were divided into three groups: PCO (sows with polycystical ovaries), OO (sows with oligocystic ovaries) and control (sows without ovarian cysts). The ovaries for evaluations were collected after slaughtering of 18 multiparous sows. Between the PCO and OO animals, statistically significant differences in numbers of the follicular cysts (FC) (8.6 vs. 1.5), follicular theca-lutein cysts (FTLC) (8.0 vs. 2.0), follicular lutein cysts (FLC) (4.5 vs. 2.0) and corpus luteum cysts (CLC) (1.7 vs. 0.4) (P< or =0.01) were noted. In the PCO sows the most common kinds of cysts were FC and FTLC (8.6 and 8.0) whilst in OO sows the cysts occurred on their ovaries on a similar level (FC - 1.6, FTLC - 2.0, FLC - 2.0). Existence of more than 10 ovarian cysts in the sows significantly decreases the frequency of physiological ovarian follicles (primary, growing and maturing) and significantly increases the pathological process of atresia on all stages of ovarian follicles development (P< or =0.01). The study did not reveal any effect of growing or decreasing number of ovarian cyst on concentrations of E(2) and P(4) in blood plasma of sows. Polycystical ovaries significantly decreased concentrations of A(4) but increased the concentration of T in blood plasma (P< or =0.01). The general presence of ovarian cysts considerably positively correlated with concentrations of E(2), T and A(4) from cysts' fluid, of all kinds of ovarian cysts and atresia of primary follicles (a correlation coefficient r from 0.72 up to 0.97, P< or =0.05). The phenomenon of ovarian cysts significantly negatively correlated with all generations of ovarian follicles (P< or =0.05). PMID- 20591582 TI - Methadone maintenance treatment: a protective factor for cocaine injection in a street-recruited cohort of heroin users. AB - OBJECTIVE: To evaluate the effect of methadone maintenance treatment (MMT) on cocaine use and cocaine injection among heroin users. METHODS: Generalized estimating equations (GEE) were used to examine the association between MMT enrollment (0, <12, >=12 months) and changes in frequency of cocaine use or injection in two consecutive follow-up visits among heroin users in the Itinere cohort, and to determine whether these changes were independent of equivalent changes in heroin use or injection. Seven multivariate models were constructed, one for each outcome variable on drug use changes. RESULTS: Of the 992 participants recruited in 2001-2003, 628 (63.3%) had at least one follow-up visit. Of these, 55.8% were enrolled in MMT at baseline and an additional 23.2% initiated MMT during follow-up. In multivariate GEE, changes significantly and positively associated with MMT enrollment were: less cocaine use [MMT<12 months (OR=1.70, 95% CI=1.17-2.48)] and less cocaine injection [MMT>=12 months (OR=2.98, 95% CI=1.51-5.89)]. Being on MMT>=12 months was negatively associated with more cocaine use (OR=0.62, 95% CI=0.38-0.99) and with more cocaine injection (OR=0.52, 95% CI=0.28-0.98). When equivalent changes in heroin were used as a covariate, the MMT effect on less cocaine use was hardly modified (OR=1.69, 95% CI=1.07 2.65), and the effect on changes in cocaine injection disappeared. CONCLUSION: MMT enrollment is a protective factor against both cocaine use and injection among heroin users. The effect of MMT on cocaine injection appears to be mediated by heroin injection, whereas its effect on cocaine use is more direct. PMID- 20591585 TI - Nutrient intake in the bovine during early and mid-gestation causes sex-specific changes in progeny plasma IGF-I, liveweight, height and carcass traits. AB - Fetal and postnatal growth are mediated by insulin-like growth factors (IGFs) and their binding proteins (IGFBPs). Maternal nutrient intake during gestation can program the postnatal IGF-axis. This may have significant economic implications for beef cattle production. We investigated the effect of high (H=240%) and low (L=70%) levels of recommended daily crude protein (CP) intake for heifers during the first and second trimesters of gestation in a two-by-two factorial design on progeny (n=68) plasma IGF-I, IGF-II, total IGFBP (tIGFBP), postnatal growth and carcass traits. Calves were heavier at birth following high CP diets during the second trimester (P=0.03) and this persisted to 29d. Plasma IGF-I concentrations of males were greater for HL compared to LL (P<0.01) and HH (P>0.04) from 29 to 657d, and for LH compared to LL from 29 until 379d (P=0.02). Exposure to low CP diets during the first trimester resulted in heavier males from 191d onwards (P=0.04) but a tendency for lighter females from 552d onwards (P=0.07) that had lighter carcass weights (P=0.04). Longissimus dorsi cross-sectional area of all carcasses was greater following exposure to low CP diets during the second trimester (P=0.04). Heifer nutrient intake during the first and second trimesters causes persistent and sex-specific programming of progeny plasma IGF-I, postnatal liveweight and carcass weight. Refining heifer nutritional programs during early gestation may optimize production objectives in progeny. PMID- 20591586 TI - Osteoporosis in people with severe mental illness: A forgotten condition. PMID- 20591587 TI - Self-infliction of faked gunshot wounds in absence of overt psychopathology. AB - Distinguishing deliberate self-inflicted body damage from assault represents a challenge to the forensic expert. Identifying a wound as self-inflicted can be particularly difficult in emergency room situations. We present the case of an individual who self-inflicted three bullet wounds, allegedly related to a shooting incident. This individual was lacking any overt psychopathology. When confronted with the facts, he confessed and explained his motivation. It is known that self-mutilation behavior can be related to particular, well systematized psychiatric disorders. However, in the absence of such a diagnosis, every suspicious wound should be carefully considered by the forensic expert as potentially self-inflicted with the intent by the "victim" of obtaining secondary gains. PMID- 20591588 TI - No association of IL-10 promoter SNP -592 and -1082 and SIDS. AB - Sudden infant death syndrome (SIDS) constitutes a considerable percentage of infant death of unknown etiology. The genetically controlled pathway of cytokine mediated response to inflammation is presumed to play a role in SIDS. The A allele of SNP -592 of the promoter region of the anti-inflammatory cytokine IL-10 has been suggested to be associated with SIDS. Herein we investigated whether we could confirm this finding by SNP genotyping a series of 123 cases of SIDS and 406 control cases. We did not find a correlation between the A allele or an A allele containing genotype of IL-10 promoter SNP -592 and SIDS which is in contrast to previous studies. Also, in concordance with previous work, no association of the A allele or A allele containing genotypes of IL-10 promoter SNP -1082 and SIDS was found. PMID- 20591589 TI - The thermal visualisation of latent fingermarks on metallic surfaces. AB - Recent published research has lead to improved techniques for recovering latent fingermarks from metallic surfaces. The present study corroborates and extends some of the work carried out by Bond [1-3], but an alternative mechanism is proposed for the thermal visualisation of fingermarks based on differential oxidation and the production of interference colours that improve contrast. Fingermarks treated at low temperature could be reheated to enhance recovery, but an upper temperature limit occurs beyond which the mark degrades. The mechanism of enhancement is discussed. PMID- 20591590 TI - Differentiation of blue ballpoint pen inks by positive and negative mode LDI-MS. AB - Usually, the differentiation of inks on questioned documents is carried out by optical methods and thin layer chromatography (TLC). Therefore, spectrometric methods were also proposed in forensic literature for the analysis of dyes. Between these techniques, laser desorption/ionization mass spectrometry (LDI-MS) has demonstrated a great versatility thanks to its sensitivity to blue ballpoint ink dyes and minimal sample destruction. Previous researches concentrated mostly on the LDI-MS positive mode and have shown that this analytical tool offers higher discrimination power than high performance TLC (HPTLC) for the differentiation of blue ballpoint inks. Although LDI-MS negative mode has already been applied in numerous forensic domains like the studies of works of art, automotive paints or rollerball pens, its potential for the discrimination of ballpoint pens was never studied before. The aim of the present paper is therefore to evaluate its potential for the discrimination of blue ballpoint inks. After optimization of the method, ink entries from 33 blue ballpoint pens were analyzed directly on paper in both positive and negative modes by LDI-MS. Several cationic and anionic ink components were identified in inks; therefore, pens were classified and compared according to their formulations. Results show that additional information provided by anionic dyes and pigments significantly increases the discrimination power of positive mode. In fact, it was demonstrated that classifications obtained by the two modes were, to some extent, complementary (i.e., inks with specific cationic dyes not necessarily contained the same anionic components). PMID- 20591591 TI - Bullets fragments identification by comparison of their chemical composition obtained using instrumental neutron activation analysis. AB - Bullets found in crime scenes are usually compared by examination of the rifling impressions produced in the barrel of the questioned firearm. When, however, a bullet is fragmented or highly deformed, the comparison of rifling micro striations cannot be performed, and the only way two compare two or more bullets is by a match of their chemical analysis. In spite of the limits of the chemical analysis methods, due to the frequent compositional lead variability of ammunition boxes, the technique still keeps its full value, both as trial element, and as an aid in the investigations. A case is reported in the present paper, in which some crushed and deformed bullets, recovered from a murder victim body, have been analyzed by Instrumental Neutron Activation Analysis. The analysis allowed the assignation of the bullets to one of the ammunitions lots owned by one of the murder suspect. PMID- 20591592 TI - A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer. AB - OBJECTIVE: In this study we evaluate the clinical response and safety profile of a regimen of docetaxel+carboplatin concurrent with radiotherapy (RT) in locally advanced squamous cell carcinoma of head and neck (HNSCC). METHODS: Between January 2006 and December 2008, we enrolled 38 patients (stage IVA: 29 patients; stage III: 9 patients). Fourteen had oral cavity cancer (tongue 10, buccal mucosa 2, alveolar ridge 1, floor of mouth 1), 10 had oropharyngeal cancer (base of tongue 5, tonsil 5), 13 had laryngeal cancer, and 1 had maxillary sinus cancer. Patients received concurrent docetaxel 15 mg/m2 1-h infusion plus carboplatin AUC of 2, 30-min infusion on days 1, 8, 15, 22, 29, and 36. RT began on day 1 of concurrent chemotherapy with 2 cGy/fraction, 5 fractions/week (total dose: 66-70 cGy). Tumor was assessed by CT scan 3 months post-completion of concurrent chemoradiotherapy. RESULTS: Thirty-five patients were evaluated (2 refused to receive all treatments, 1 had serious adverse event [rash, wheezing] from docetaxel first dose). The primary study endpoint of clinical response was achieved in 26 (74.3%) patients, 6 (17.1%) had stable disease, and 3 (8.6%) had disease progression. The 2-year disease-free survival was 62.9% (CI: 45.85 79.95%). The 2-year overall survival was 64.1% (CI: 43.52-84.68%). The most common Grade 3 toxicities were mucositis, xerostomia and dysphagia (13.9% each) and dermatitis (11%). No Grade 4 toxicities were observed. CONCLUSION: In conclusion, this study with a limited number of patients, docetaxel+carboplatin concurrent with RT appears to show acceptable activity and is generally well tolerated in patients with locally advanced HNSCC. PMID- 20591593 TI - Preoperative three-dimensional CT angiography to distinguish between an aberrant subclavian artery and a double aortic arch in thyroid surgery: Report of 2 cases. AB - A non-recurrent inferior laryngeal nerve (NRILN), a very rare anatomic variation, is easily damaged during thyroid surgery. Due to impairments during embryonic development, a NRILN is frequently associated with an aberrant subclavian artery. Thus, an aberrant subclavian artery is now regarded as an important vascular anomaly for predicting the presence of a NRILN using various imaging modalities. However, precise imaging is often necessary as other vascular anomalies, such as a double aortic arch, can cause difficulties in discriminating between an aberrant subclavian artery and other anatomic variations. For this reason, computed tomography (CT) is usually necessary before thyroid surgery. but, to take more precise images, newly developed techniques such as computed tomography angiography (CTA) are needed. To indentify NRILNs, we performed CTA preoperatively in two patients with thyroid cancer. CTA demonstrated an aberrant subclavian artery with an associated NRILN in one patient and a double aortic arch with a recurrent inferior laryngeal nerve (RILN) in the second patient. Thyroid surgery was successful, and the laryngeal nerve was preserved in both patients. Preoperative CTA is much safer and less time-consuming than catheter angiography. Also, CTA is a cost-effective three-dimensional imaging modality for identifying aberrant subclavian arteries associated with NRILNs, as compared with double aortic arches associated with RILNs. PMID- 20591594 TI - Natural course of positional vertigo in patients with apogeotropic variant of horizontal canal benign paroxysmal positional vertigo. AB - OBJECTIVE: The purpose of this study was to assess the natural course of positional vertigo in patients with the apogeotropic variant of horizontal canal type of benign paroxysmal positional vertigo (AH-BPPV), which is reported to be more refractory to physiotherapy than the geotropic variant of horizontal canal type of BPPV (GH-BPPV). METHODS: 14 patients with AH-BPPV treated without physiotherapy were asked to visit the hospital every 2 weeks. At every follow-up visit, they were interviewed and positional nystagmus was assessed. After the disappearance of positional nystagmus, patients were asked about the time of cessation of the positional vertigo. Thus, the primary outcomes were evaluated by the self-reported onset and remission of positional vertigo. The time course of remission of positional vertigo was then calculated. RESULTS: The average and median period from the onset to natural remission of positional vertigo in patients with AH-BPPV was 13 and 7 days, respectively. CONCLUSION: We have already reported that the average and median period from the onset to natural remission of positional vertigo in patients with GH-BPPV was 16 and 7 days, respectively (Imai et al., 2005 [8]). Thus, the natural course of AH-BPPV is not as refractory as that of GH-BPPV. PMID- 20591596 TI - Pediatric neoplasms of abdomen. Editorial. PMID- 20591595 TI - Augmented startle responses in opsoclonus-myoclonus syndrome. AB - We report a 3-year-old boy with opsoclonus-myoclonus syndrome (OMS) who presented with exaggerated startle responses to unexpected auditory stimuli during an episode of myoclonic status. An augmented blink reflex was also observed clinically and electrophysiologically. Based on the assumption that hyperexcitability in the lower pontine tegmentum may be responsible for the acoustic startle and blink reflex in OMS, we considered that increased excitability of independent but neighboring structures, including the pontine paramedian reticular formation, may cause OMS symptoms. PMID- 20591597 TI - Intraspinal primitive neuroectodermal tumor: imaging findings in six cases. AB - PURPOSE: To retrospectively review CT and MRI findings in a series of six intraspinal primitive neuroectoderal tumors and to find out their radiological features. METHODS: CT and MRI of six patients with surgically and pathologically proved intraspinal primitive neuroectoderal tumor were retrospectively reviewed. The tumor location, morphological features, signal intensity, calcification, contrast enhancement characteristics, involvement of paraspinal soft tissues and adjacent bony structures were assessed. RESULTS: Of six patients, four had extradural lesions and two had intradural, extramedullary lesions. Most lesions were well defined and manifested heterogeneous iso- or hypo-intense signal on T1 weighted imaging and hyper-intense signal on T2-weighted imaging and moderate attenuation on CT, and were heterogeneously enhanced after contrast enhancement. The lesion extending through the intervertebral foramen with a large paraspinal soft tissue mass formed was found in four patients and vertebral bone involvement was seen in four patients. CONCLUSIONS: Although imaging findings are not specific of intraspinal primitive neuroectoderal tumor, this diagnosis could be suggested when MR imaging depicts an intradural, extramedullary or extradural large well-circumscribed mass which extends out from intervertebral foramen and invades paraspinal soft tissues or vertebral bones in a young patient. PMID- 20591598 TI - CT characteristics of primary retroperitoneal neoplasms in children. AB - Primary retroperitoneal neoplasms are uncommon in children. Retroperitoneal neoplasms are either mesodermal, neurogenic, germ cell ectodermal or lymphatic in origin. In general, primary retroperitoneal neoplasms in children have different spectrum and prevalence compared to those in adults. Neuroblastoma, rhabdomyosarcoma, benign teratoma and lymphoma are the common retroperitoneal neoplasms. In this review, the clinical and CT futures of common retroperitoneal neoplasms in children are described. Coarse, amorphous, and mottled calcification are very common in neuroblastoma. Paraganglioma tends to show marked and early enhancement and may present with clinical symptoms associated with the excess catecholamine. Sarcomas are often very large and have heterogeneous appearance. Imaging cannot be reliably used to identify the type of retroperitoneal sarcomas due to overlapped radiographic features. In children, lipoblastoma is the most common lipomatous tumor in the retroperitoneum. The percentage of visible fat in tumor varies depending on the cellular composition of the lesion. The CT characteristics of teratoma are quite variable, which may be cystic, solid, on a combination of both. Typically teratoma appears as a large complex mass containing fluid, fat, fat-fluid level, and calcifications. Lymphoma is often homogeneous on both enhanced and unenhanced CT scans. Necrosis and calcification are rare on CT. In conclusion, making a final histological diagnosis of retroperitoneal tumor base on CT features is not often possible; however, CT can help to develop a differential diagnosis and determine the size and extent of the retroperitoneal neoplasms. PMID- 20591599 TI - Recognition and management of the spectrum of acute laryngeal trauma. AB - BACKGROUND: Blunt laryngeal trauma frequently takes place in the setting of more significant injuries. In the setting of multiple injuries or, more importantly, as an isolated event, missed injuries to the laryngotracheal complex can have devastating results. More importantly, underestimation of the severity of injury can result in an airway that becomes quite difficult to manage. However, early recognition and management of laryngotracheal injuries can result in minimal morbidity and the need for minimal long-term intervention. OBJECTIVES: Our goal is to heighten awareness of the severity of blunt laryngotracheal trauma and reduce both acute and long-term sequelae. CASE REPORT: We present a series of cases representing a spectrum of seemingly benign neck injuries requiring a diversity of interventions. The cases represent worsening gradations of laryngeal trauma, and the differing presentation, work-up, and management scenarios are discussed. CONCLUSIONS: Expedient evaluation, treatment, and management of blunt laryngeal trauma results in favorable outcomes. Awareness of the potential for significant injury in the presence of benign examination based on the history of injury and confirmed by radiographic or endoscopic evaluation is paramount. Although minimal findings on examination and stable patients in the setting of blunt trauma to the neck may be as innocuous as it seems, the severity of injury may "lie beneath." PMID- 20591600 TI - In vitro testing of a newly developed arteriovenous double-outflow graft. AB - INTRODUCTION: The long-term prognosis of arteriovenous polytetrafluoroethylene (PTFE) hemodialysis grafts remains poor, causing significant morbidity and costs. The high failure rate is due to a stenosis development of the graft-vein anastomosis, consisting of two pathophysiologically separate and characteristic lesions emerging from two main mechanisms: development of intimal hyperplasia in the vein and pseudointima in the graft. We developed a new venous anastomotic graft design that combines a flow diffuser and flow division, thereby creating a double-channel graft (Bi-Flow graft) and tested it in vitro. METHODS: In vitro experiments have been performed using silastic models of six different anastomotic configurations (straight end-to-side, cuffed Venaflo-type, large and small diffuser, and large and small Bi-Flow) inserted into a pulsatile-flow circuit. The silastic models were created using a computerized numerical control design approach, varying only the venous anastomoses. Velocity fields and shear stresses were obtained using particle image velocimetry, and volumetric flow rates through the models were measured using an ultrasound flowmeter. RESULTS: The hooded graft configurations showed significantly lower shear forces than did the end-to-side anastomosis. The shear stresses in the straight end-to-side graft were as high as arterial wall stresses. Large separation areas were present in the hooded grafts, except for the small Bi-Flow graft, which showed only isolated separation zones near the baffle used to divide the flow. The double-channel grafts exhibited a parabolic flow profile consisting of laminar flow in the double-outflow portion of the model's laminar flow pattern through the venous anastomosis. A marked flow separation was present in the large Bi-Flow model. Volumetric flow measurements revealed an average flow increase of 21% through the small Bi-Flow graft, which was attributed to the optimization of flow dynamics and pattern within the venous anastomosis of the double-channel graft. CONCLUSION: The new arteriovenous Bi-Flow graft design addresses two major problems responsible for the development of venous stenosis of prosthetic hemodialysis grafts in vitro. The new graft design should be further investigated in animal studies. PMID- 20591601 TI - Long-term outcomes of diabetic patients undergoing endovascular infrainguinal interventions. AB - OBJECTIVE: Diabetes mellitus (DM) has traditionally predicted poor outcomes after lower extremity revascularization for peripheral vascular disease (PVD). This study assessed the influence of DM on long-term outcomes of percutaneous transluminal angioplasty, with or without stenting (PTA/stent), in patients with PVD. METHODS: From January 2002 to December 2007, 920 patients underwent 1075 PTA/stent procedures. Patients were stratified into DM and non-DM cohorts. Study end points included primary patency (PP), assisted patency (AP), limb salvage, and survival and were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: There were 533 DM and 542 non-DM limbs. Median follow-up was 34 months. Overall, the 5-year actuarial PP was 42% +/- 2.4%, AP was 81% +/- 2.0%, limb salvage was 89% +/- 1.6%, and survival was 60% +/- 2.4%. On univariate analysis, DM vs non-DM was associated with inferior 5-year PP (37% +/- 3.4% vs 46% +/- 3.3%; P = .009), limb salvage (84% +/- 2.6% vs 93% +/- 1.8%, P < .0001), and survival (52% +/- 3.5% vs 68% +/- 3.1%, P = .0001). AP did not differ between DM and non-DM patients (P = .18). In the entire cohort, DM (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.01-1.54; P = .04), single-vessel peroneal runoff (HR, 1.54; 95% CI, 1.16-2.08; P = .003), and dialysis (HR, 1.59; 95% CI, 1.10 2.33; P = .02) were associated with decreased PP on multivariate analysis. The only variables on multivariate analysis to predict limb loss and death were critical limb ischemia (HR, 9.09; 95% CI, 4.17-20.00; P < . 0001; HR, 2.99; 95% CI, 2.01-4.44; P < .0001, respectively) and dialysis (HR, 2.94; 95% CI, 1.39 5.00; P = .003; HR, 4.24; 95% CI 2.80-6.45; P < .0001, respectively). CONCLUSIONS: DM is an independent predictor of decreased long-term primary patency after PTA/stent. Although acceptable assisted patency rates can be achieved with close surveillance and reintervention, long-term limb salvage remains inferior in diabetic patients compared with non-diabetic patients due to a more severe clinical presentation and poor runoff. PMID- 20591602 TI - The effect of warfarin therapy on endoleak development after endovascular aneurysm repair (EVAR) of the abdominal aorta. AB - OBJECTIVES: The presence of an endoleak after endovascular abdominal aortic aneurysm (AAA) repair (EVAR) may predispose to sac expansion and potential sac rupture. The incidence of endoleak after AAA repair can be as high as 20% to 30%. We investigated whether warfarin anticoagulation was an independent risk factor for endoleak after EVAR for AAA. METHODS: All AAA patients who underwent elective EVAR were prospectively followed-up. Data for demographics, clinical comorbidities, outcomes, EVAR devices, and anticoagulation methods were recorded. All patients underwent routine follow-up at 1, 6, and 12 months and annually thereafter. Computed tomography angiography (CTA) with 3-dimensional (3D) volumetric analysis was also completed. RESULTS: During a 7-year period, 127 consecutive patients with infrarenal AAAs who underwent EVAR were monitored for a mean of 2.14 years. The average age at the time of EVAR was 73.8 years. Warfarin therapy alone was administered to 24 patients, and anticoagulation with antiplatelet therapy alone was administered to 103. During the study period, 38 (29.9%) endoleaks were documented. The overall endoleak rate was 13 of 24 in the warfarin group and 25 of 103 in the antiplatelet group (P = .004). CTA 3D volumetric aneurysm sac analysis showed an increase of 16.09% in the warfarin study group and a reduction of 9.71% in the antiplatelet group (P = .04). CONCLUSIONS: Anticoagulation with warfarin appears to be linked to an increased risk for the development of endoleak after EVAR, specifically type II. Volumetric analysis showed warfarin therapy also contributed to persistent aneurysm sac expansion. These data suggest that patients who require warfarin anticoagulation for other indications should be advised that they might be at an increased risk for the development of endoleaks, subsequent secondary interventions, persistent sac expansion, and possible delayed sac rupture. PMID- 20591603 TI - Catheter-based neurosalvage for acute embolic complication during carotid intervention. AB - OBJECTIVES: Iatrogenic emboli may be released during carotid intervention, causing permanent neurologic complications and catastrophic outcomes. This article reports the procedural details and clinical results of our series of neurosalvage techniques to manage thromboembolic events during carotid procedures. METHODS: Between March 2003 and December 2007, 342 patients (283 men, 72.1 +/- 8.9 years old, 121 symptomatic) underwent percutaneous stent deployment in 407 cervical internal carotid arteries in our institution. Visible distal embolization with flow occlusion caused neurologic complications in 10 patients (2.5%), and a structured and stepwise neurosalvage approach was attempted. RESULTS: Guidewire fragmentation and microcatheter injection of heparin and nitroglycerin were performed in all 10 patients as step 1. Intra-arterial thrombolysis was given in four patients and balloon angioplasty in five, as step 2. Intracranial stenting was done in one patient as the last step. Successful angiographic recanalization (Thrombolysis in Myocardial Infarction [TIMI] grade 2 3) occurred in 9 of 10 (90%). Residual neurologic sequel was observed in five, including three patients with hemorrhage complications (1 received emergent craniotomy). There was no neurologic mortality in this series. CONCLUSIONS: Acute embolic complication during carotid artery stenting can be managed by catheter based neurosalvage with effective angiographic recanalization and marginal clinical success. PMID- 20591604 TI - Peritoneal wash cytology in gastric carcinoma. Prognostic significance and therapeutic consequences. AB - BACKGROUND AND AIMS: The prognosis of patients with gastric cancer is poor, even following curative resection, and is related primarily to the extent of disease at presentation. In locally advanced gastric tumors, peritoneal lavage cytology (PLC) is a relevant prognostic factor. The Authors present their results of peritoneal washing cytology, evaluating the prognostic value of this technique, and discussing the clinical impact. PATIENTS AND METHODS: From July 2003 to May 2008, results of PLC in 64 patients with histologically proven primary gastric adenocarcinomas were analyzed. At laparotomy the abdomen was irrigated with 200 ml of normal saline, and >=50 ml were aspirated and examined by means of cytology and immunocytopathology. RESULTS: PLC was positive in 7 cases (11%). Overall, 86% of patients with a positive PLC had a pT3/pT4 tumor and 100% with a positive PLC had an N-positive tumor (p < 0.001); 71% of patients with a positive PLC had a grade G3/G4 tumor (p = 0.001). At a median follow-up of 32 months, the cumulative 5-year survival was 28%. The median survival of patients presenting positive PLC (19 months) was significantly lower than that of patients with negative peritoneal cytology (38 months) (p = 0.0001). Multivariate analysis identified cytology as a significant predictor of outcome (p = 0.018). CONCLUSIONS: Results in the present series demonstrated that patients with a positive peritoneal cytology had advanced disease and poor prognosis, thus indicating that patients with locally advanced gastric cancer should undergo staging laparoscopy and PLC examination in order to select those requiring more aggressive treatment. Future therapeutic strategies should include PLC examination in preoperative staging, in order to select patients for more aggressive treatment. PMID- 20591605 TI - Should specialized oncogeriatric surgeons operate older unfit cancer patients? AB - This rapidly expanding cancer patient group benefits of specialist care. The use of frailty assessment tools is mandatory in clinical practice and in medical reporting. A fair risk-benefits balance should be kept in mind at all times; patients' requests and expectations should be prioritised. Aggressive surgical treatment should not be neglected in principle, but alterative management should be considered at all times. PMID- 20591606 TI - [Hand ischaemia after radial artery catheterization: don't elude Allen test]. PMID- 20591607 TI - [Adrenocortical insufficiency and abdominal pain]. AB - The adrenocortical insufficiency may mimic an acute surgical abdomen. We report the case of 20-year-old patient, who presented abdominal pain syndrome, associated with isolated moderate hyponatremia (135 mmol/l). The first diagnostic given is an appendicular syndrome, and she underwent surgery. Given the persistence of abdominal pain syndrome and hyponatremia (133 mmol/l), adrenocortical insufficiency was sought. The follow-ups were simple after the introduction of replacement therapy. PMID- 20591608 TI - Radiologic and pathological correlation of staging of rectal cancer with 3 Tesla magnetic resonance imaging. AB - PURPOSE: To assess the sensitivity and specificity of 3 Tesla magnetic resonance imaging (MRI) in the prediction of extramural spread and metastatic adenopathy in rectal carcinoma. MATERIALS AND METHODS: This was a prospective cohort study that included forty consecutive patients with rectal carcinoma from the Department of Colorectal Surgery. Three Tesla (3T) MRI was performed on these patients after a 4-hour fast and cleansing water enema. TI-weighted and T2-weighted images were obtained with high-resolution images T2-weighted sequences through the pelvis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 3T MRI for prediction of metastatic adenopathy and extramural spread were calculated. The TNM staging based on MRI was compared with histopathology of the resected specimen (taken as the criterion standard). RESULTS: In our study, sensitivity, specificity, PPV, and NPV of 3T MRI for prediction of metastatic adenopathy were 100%, 78.3%, 77.3%, and 100%, respectively. Sensitivity, specificity, PPV, and NPV of 3T MRI for prediction of extramural tumour spread were 100% and 20%, 89.7% and 100%, respectively (ie, prediction of stages T3 and above). CONCLUSION: MRI allows accurate measurement of the depth of extramural tumour spread. In the assessment of metastatic adenopathy, however, MRI has a low specificity. This study shows that MRI is unlikely to miss any significant parameter in staging of rectal carcinoma. However, it has a tendency to overstage extramural spread of tumour. PMID- 20591609 TI - Chest radiographs are valuable in demonstrating clinically significant pacemaker complications that require reoperation. AB - PURPOSE: To evaluate the utility of chest radiography in demonstrating clinically significant pacemaker complications that required reoperation. METHODS: In this retrospective case-controlled series, we identified 14 consecutive adults who required pacemaker reoperation and who had chest radiographs available for review (6 men, 8 women; mean age, 71 years [range, 43-95 years]). Ten patients had pacemakers implanted at our institution, and 4 were referred for reoperation. Forty-two controls, 3 for each patient, had postoperative chest radiographs and normal device function (25 men, 17 women; mean age 76 years [range, 37-96 years]). All postoperative chest radiographs, including 1-year follow-ups, were blindly reviewed by at least 2 of 4 radiologists for lead perforation and position of right atrial and right ventricular leads. Follow-up radiographs were assessed for lead perforation, lead displacement, and lead fracture. Data were analysed by using the Fisher exact test. RESULTS: Of the patients, 1.7% (10/581) required reoperation for pacemaker dysfunction (noncapture, oversensing, abnormal atrial and ventricular thresholds, failing impedance), extracardiac stimulation, and lead perforation and/or displacement. There were no lead fractures. Chest radiographs demonstrated pacemaker complications in 57% of patients (8/14) at a median of 2 days (<1-32 days) after implantation and in 5% of the controls (2/42) (P < .0001). None of the abnormalities were noted on the official reports. Among subgroups, chest radiographs were abnormal for the following indications: pacemaker dysfunction in 4 of 7 patients versus 0 of 21 controls (P = .0017), extracardiac stimulation in 1 of 3 patients vs 0 of 9 controls (P = .25), and lead perforation and/or displacement in 3 of 4 patients vs 2 of 12 controls (P = .06). CONCLUSIONS: Chest radiographs are useful after pacemaker placement and demonstrate the majority of complications that require reoperation. Familiarity with the expected normal position of the leads, appearances of pacemaker complications, and comparison with prior radiographs is crucial in rendering a correct diagnosis that guides patient management. PMID- 20591610 TI - Fluid levels in pediatric imaging: a pictorial review. AB - Fluid levels appearances are not uncommon findings in different diagnostic modalities including radiography, ultrasound, computed tomography, and magnetic resonance imaging. The significance of such signs varies according to the involved sites and the clinical settings. Familiarity with their imaging features and their diagnostic value as well as their clinical implication are of paramount importance for the radiologist and the clinician. We aim to review a spectrum of examples of fluid levels encountered with different modalities in paediatric imaging and discuss their appearances and clinical significances. PMID- 20591611 TI - Diffraction enhanced X-ray imaging of the distal radius: a novel approach for visualization of trabecular bone architecture. PMID- 20591612 TI - "Asymptomatic" pseudotumors after metal-on-metal hip resurfacing arthroplasty: prevalence and metal ion study. AB - Symptomatic abnormal periprosthetic soft-tissue reactions ("pseudotumors") have been reported after metal-on-metal hip resurfacing arthroplasty (MoMHRA). The aims of this study were (1) to determine the prevalence of asymptomatic pseudotumors after MoMHRA and (2) to measure metal ion levels in these patients. A total of 201 hips in 158 patients were evaluated at a mean follow-up of 61 months (range, 36-88) using ultrasound/magnetic resonance imaging and serum/hip aspirate cobalt and chromium measurements. Pseudotumors found in 7 patients (4%) were associated with significantly higher cobalt and chromium levels and inferior functional scores. Elevated levels of cobalt and chromium ions suggest that pseudotumors are associated with increased wear generated from metal-on-metal articulations. Clinicians need to be aware of pseudotumors as a differential diagnosis during clinical evaluation of MoMHRA patients, and further imaging such as ultrasound or magnetic resonance imaging is recommended to confirm the diagnosis. PMID- 20591613 TI - Shame- and guilt-proneness: relationships with anxiety disorder symptoms in a clinical sample. AB - Researchers postulate that both shame and guilt are emotions important to anxiety disorders. Extant data, however, indicate that guilt-proneness shares non significant relationships with psychopathology symptoms after controlling for shame-proneness. To further investigate the relevance of shame and guilt to the anxiety disorders domain, the current study examined associations between shame- and guilt-proneness and anxiety disorder symptoms using data from patients (N=124) with primary anxiety disorder diagnoses. Results indicated that only symptoms of social anxiety disorder (SAD) and generalized anxiety disorder (GAD) shared significant relations with shame-proneness after controlling for other types of anxiety disorder symptoms, depression symptoms, and guilt-proneness. Further, changes in shame-proneness during treatment were found to share significant relations with changes in obsessive-compulsive disorder, SAD, and GAD symptoms. The current results indicate that shame is more relevant to symptoms of the anxiety disorders domain than is guilt. The implications of these results for the conceptualization and treatment of anxiety disorders are discussed. PMID- 20591614 TI - A randomized controlled evaluation of a spiritually integrated treatment for subclinical anxiety in the Jewish community, delivered via the Internet. AB - OBJECTIVE: This study evaluated the efficacy of a spiritually integrated treatment (SIT) for subclinical anxiety in the Jewish community. METHOD: One hundred and twenty-five self-reported religious Jewish individuals with elevated levels of stress and worry received SIT (n=36), progressive muscle relaxation (PMR, n=42), or a waitlist control condition (WLC, n=47). SIT and PMR participants accessed Internet-based treatment on a daily basis for a period of 2 weeks. All participants completed self-report assessments at pre-treatment (T1), post-treatment (T2), and 6-8-week follow-up (T3). RESULTS: SIT participants reported large improvements in primary (stress and worry) and secondary (depression and intolerance of uncertainty) outcomes, and moderate improvements in spiritual outcomes (positive/negative religious coping; trust/mistrust in God). SIT participants reported greater belief in treatment credibility, greater expectancies from treatment and greater treatment satisfaction than PMR participants. SIT participants also reported better improvements in both primary outcomes (stress and worry), one of two secondary outcomes (intolerance of uncertainty), and two of four spiritual outcomes (positive religious coping and mistrust in God) compared to the WLC group, whereas PMR and WLC participants did not differ on most outcomes. CONCLUSIONS: Results of this investigation offer initial support for the efficacy of SIT for the treatment of subclinical anxiety symptoms among religious Jews. Results further suggest that it is important to incorporate spiritual content into treatment to help facilitate the delivery of psychotherapy to religious individuals. PMID- 20591615 TI - Mirror visual feedback induces lower neuromuscular activity in children with spastic hemiparetic cerebral palsy. AB - The study examined the effects of mirror feedback information on neuromuscular activation during bimanual coordination in eight children with spastic hemiparetic cerebral palsy (SHCP) and a matched control group. The 'mirror box' creates a visual illusion, which gives rise to a visual perception of a zero lag, symmetric movement between the two arms. The study incorporated two additional visual feedback conditions by placing a glass or opaque screen between the arms. During bilateral symmetric circular arm movements mirror visual feedback induced lower neuromuscular intensities in the shoulder muscles of the less impaired arm of children with SHCP compared to the other visual conditions. In addition, the mirror lead to shorter relative durations of eccentric and concentric activity in the elbow muscles of the more impaired arm, whereas no effects of visual feedback were found in a matched control group. These results suggest that replacing veridical visual information of the more impaired arm with a mirror reflection of the less impaired arm improves the motor control of children with SHCP during interlimb coupling. The effects of the availability of visual feedback in individuals with hemiparesis are discussed with reference to: (1) increase ipsilateral motor cortex excitability and (2) congruence between afferent (visual) feedback and the internal copy of the motor commands. PMID- 20591616 TI - Do deaf adults with limited language have advanced theory of mind? AB - Previous studies show that deaf children have deficits in false belief understanding due to their language impairment. However, it is not clear whether deaf adults still have problems in advanced theory of mind (ToM). The present study examined deaf adults' performance on three aspects of advanced ToM. All of the deaf groups lacking mental state language tended to perform worse than the hearing group on explicit mental state understanding. Deaf groups with either vocabulary skill or interpersonal experience from early years were similar to the hearing group in implicit mental state reasoning. Individuals frequently using syntactic complements or having interpersonal experience with hearing people from early years tended to use ToM better. Moreover, language ability was the only predictor for explicit rather than implicit mental state understanding. Sufficient language is not necessary for all aspects of advanced ToM. Rich interpersonal experience as a substitute for language may facilitate deaf adults' advanced ToM. PMID- 20591617 TI - Isolated left ventricular apical hypoplasia: a newly recognized unclassified cardiomyopathy. AB - We describe two relatively asymptomatic cases diagnosed with the newly recognized unclassified cardiomyopathy, isolated left ventricular apical hypoplasia. The disease has been described mainly in cardiac magnetic resonance, whereas this study presents the echocardiographic characteristics of this new cardiomyopathy. PMID- 20591618 TI - Two-dimensional and Doppler echocardiography reliably predict severe pulmonary regurgitation as quantified by cardiac magnetic resonance. AB - BACKGROUND: The grading of pulmonary regurgitation (PR) severity by two dimensional (2D) and Doppler echocardiography is not standardized. Cardiovascular magnetic resonance imaging is the clinical gold standard for PR quantification. The purpose of this study was to determine the best 2D and Doppler echocardiographic predictors of severe PR. METHODS: Thirty-six patients with tetralogy of Fallot or pulmonary valve stenosis with prior pulmonary valvuloplasty or transannular or subannular patch repair underwent 2D and Doppler echocardiography and cardiovascular magnetic resonance. Two-dimensional and Doppler echocardiographic measurements used to predict severe PR included diastolic flow reversal in the main or branch pulmonary arteries, PR jet width > or = 50% of the pulmonary annulus, PR pressure half-time < 100 ms, and PR index < 0.77. RESULTS: With the exception of PR index, all indices were significant independent predictors of severe PR. The best univariate predictor of severe PR was branch pulmonary artery diastolic flow reversal. CONCLUSION: Two-dimensional and Doppler echocardiography reliably identified severe PR in this cohort. PMID- 20591620 TI - The different faces of echocardiographic left ventricular hypertrophy: clues to the etiology. AB - Left ventricular hypertrophy is a nonspecific physiologic or maladaptive cardiac response to a large array of stimuli mediated by exercise and numerous cardiac and systemic diseases. Hypertrophy, however, is not uniform. Rather, depending on the underlying pathologic mechanism, it may display unique morphologic and functional characteristics. The precise characterization and quantification of left ventricular hypertrophy may therefore allow a more timely diagnosis of the underlying condition. The clinical reference standard to assess left ventricular hypertrophy is echocardiography, but a comprehensive description of how to approach this frequent finding in clinical practice is lacking. The current review systematically describes the typical echocardiographic patterns of important types of cardiac hypertrophy using both established and advanced imaging modalities, thus guiding clinicians' path to early diagnosis. PMID- 20591619 TI - Low cardiovascular risk is associated with favorable left ventricular mass, left ventricular relative wall thickness, and left atrial size: the CARDIA study. AB - BACKGROUND: Echocardiographic measures of left ventricular (LV) mass and relative wall thickness and left atrial (LA) size predict future cardiovascular morbidity and mortality. The aim of this study was to compare young adults with low cardiovascular risk (body mass index, 18.5-24.9 kg/m(2); blood pressure < 120/80 mmHg; no tobacco use, no diabetes, and physical fitness) with those without these characteristics with regard to LV mass and relative wall thickness and LA size, to determine the protective effect of a healthy lifestyle on the development of these characteristics. METHODS: Cross-sectional assessment of 4059 black and white men and women aged 23 to 35 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study at the year 5-examination, when risk factors were measured, and echocardiography to assess LV mass and relative wall thickness were performed. Physical fitness was measured at baseline using a symptom-limited maximal treadmill test. All other covariates were measured concurrently with echocardiography. RESULTS: Gender, body mass index, and systolic blood pressure were associated with LV mass and relative wall thickness and LA size in multivariate models. Additional correlates of LV mass/height(2.7) ratio were tobacco use, resting heart rate (inverse), self-reported physical activity, gender (male higher), and age. Age was associated with LV relative wall thickness but not other measures of LV size. Additional correlates of LA diameter/height ratio were tobacco use, resting heart rate (inverse), serum glucose, and self reported physical activity. Seven hundred ninety of 4059 subjects (19%) were classified as having low risk; black race was less likely in the low-risk group. Those with low risk had lower LV mass/height(2.7) ratios (32.0 vs 34.6 g/m(2.7), P < .0001), better LV relative wall thickness (0.33 vs 0.35, P < .0001), and lower LA diameter/height ratios (2.02 vs 2.08 cm/m, P < .01). CONCLUSIONS: A low cardiovascular risk profile in young adulthood is associated with more favorable LV mass, LV relative wall thickness, and LA size. This may be one mechanism of lifestyle protection against cardiovascular morbidity and mortality. PMID- 20591621 TI - Carotid ultrasound identifies high risk subclinical atherosclerosis in adults with low framingham risk scores. AB - BACKGROUND: Worldwide, cardiovascular (CV) disease remains the most common cause of morbidity and mortality. Although effective in predicting CV risk in select populations, the Framingham risk score (FRS) fails to identify many young individuals who experience premature CV events. Accordingly, the aim of this study was to determine the prevalence of high-risk carotid intima-media thickness (CIMT) or plaque, a marker of atherosclerosis and predictor of CV events, in young asymptomatic individuals with low and intermediate FRS (<2% annualized event rate) using the carotid ultrasound protocol recommended by the American Society of Echocardiography and the Society of Vascular Medicine. METHODS: Individuals aged < or = 65 years not taking statins and without diabetes mellitus or histories of coronary artery disease underwent CIMT and plaque examination for primary prevention. Clinical variables including lipid values, family history of premature coronary artery disease, and FRS and subsequent pharmacotherapy recommendations were retrospectively collected for statistical analysis. RESULTS: Of 441 subjects (mean age, 49.7 + or - 7.9 years), 184 (42%; 95% confidence interval, 37.3%-46.5%) had high-risk carotid ultrasound findings (CIMT > or = 75th percentile adjusted for age, gender, and race or presence of plaque). Of those with the lowest FRS of < or =5% (n = 336) (mean age, 48.0 + or - 7.6 years; mean FRS, 2.5 + or - 1.5%), 127 (38%; 95% confidence interval, 32.6%-43.0%) had high-risk carotid ultrasound findings. For individuals with FRS < or = 5% and high-risk carotid ultrasound findings (n = 127; mean age, 47.3 + or - 8.1 years; mean FRS, 2.5 + or - 1.5%), lipid-lowering therapy was recommended by their treating physicians in 77 (61%). CONCLUSIONS: Thirty-eight percent of asymptomatic young to middle-aged individuals with FRS < or = 5% have abnormal carotid ultrasound findings associated with increased risk for CV events. Pharmacologic therapy for CV prevention was recommended in the majority of these individuals. The lack of radiation exposure, relatively low cost, and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for CV risk stratification in young to middle-aged adults with low FRS. PMID- 20591622 TI - An evaluation of transmitral and pulmonary venous Doppler indices for assessing murine left ventricular diastolic function. AB - With the continued development of genetically engineered mouse models of cardiac disease, further advancement of noninvasive techniques for evaluating cardiac diastolic dysfunction in these models would be valuable. Therefore, we performed comprehensive transmitral and pulmonary venous Doppler echocardiographic studies to devise novel indices of diastolic function in a mouse model with cardiac hypertrophy, which were validated against invasively measured hemodynamic parameters. We examined 10 HopX(Tg) transgenic mice with diastolic dysfunction and 10 age-matched controls sedated with 1% to 2% isoflurane (male, age 14-18 weeks). These studies revealed that the acceleration time of the transmitral Doppler E-wave was the best Doppler parameter for unmasking LV diastolic dysfunction in HopX(Tg) mice. This is the first study to assess the utility of the acceleration time of the E-wave and pulmonary venous Doppler echocardiography as a primary diagnostic modality for assessing murine diastolic function. PMID- 20591623 TI - Percutaneous closure of a left atrial appendage pseudoaneurysm. AB - Atrial dissections and pseudoaneurysms are rare complications of cardiac surgery. The authors describe the case of a patient after mitral valve replacement who presented with a left atrial appendage pseudoaneurysm. This case represents the first known closure of an atrial pseudoaneurysm with a percutaneous septal occluder device. PMID- 20591624 TI - Effect of synergic dietary calcium enrichment and induced ferropenic anemia on antioxidant enzymes activity in rats. AB - OBJECTIVE: The aim of this study was to examine the synergism of dietary calcium enrichment (added to goat's or cow's milk) and induced nutritional ferropenic anemia on oxidative status. METHODS: Control rats and rats with induced nutritional ferropenic anemia were fed for 14 d with diets containing normal (5000 mg/kg) or double (10 000 mg/kg) the recommended calcium content. Thiobarbituric acid-reactive substances in plasma were measured, as were the activities of the antioxidant enzyme catalase, copper/zinc superoxide dismutase, and glutathione peroxidase in erythrocyte cytosol. RESULTS: Dietary calcium enrichment did not affect oxidative stress as assessed by thiobarbituric acid reactive substances; however, it significantly upregulated the activities of some antioxidant enzymes examined in the erythrocyte cytosol. In particular, adding calcium to standard or milk-based diets significantly increased glutathione peroxidase activity in control and anemic rats and copper/zinc superoxide dismutase activity in control rats. CONCLUSION: The increased activities of glutathione peroxidase and copper/zinc superoxide dismutase induced by dietary calcium enrichment suggest that calcium supplementation may protect against oxidative stress even in nutritionally induced ferropenic anemia. PMID- 20591625 TI - Low-dose creatine supplementation enhances fatigue resistance in the absence of weight gain. AB - OBJECTIVE: We examined the effects of 6 wk of low-dose creatine supplementation on body composition, muscle function, and body creatine retention. METHODS: Twenty healthy men and women (21 +/- 2 y old) were randomized to receive creatine (0.03 g . kg(-1) . d(-1); n = 10, 4 women) or placebo (n = 10, 4 women) for 6 wk in a double-blind placebo-controlled fashion. Participants were tested on two occasions before supplementation to establish a reliable baseline, and then were retested after supplementation. Testing included body composition, maximal strength (three-repetition maximal concentric knee extension at 180 degrees/s), muscle fatigue (five sets of 30 concentric knee extensions at 180 degrees/s), and plasma creatine concentration. RESULTS: There were no significant differences in body mass, fat-free mass, fat mass, body fat percentage, total body water, or maximal strength in either group from before to after supplementation (all P > 0.05). After supplementation, plasma creatine increased significantly in the creatine group (+182%, P = 0.03), with no difference in the placebo group. Compared with baseline values, creatine-supplemented volunteers were more resistant to fatigue during sets 2 (7%), 3 (9%), 4 (9%), and 5 (11%) (all P < 0.05). In placebo-supplemented participants, there was no improvement in fatigue resistance during sets 2 (0%), 3 (1%), 4 (0%), and 5 (-1%) (all P > 0.05). CONCLUSION: Ingesting a low dose (~2.3 g/d) of creatine for 6 wk significantly increased plasma creatine concentration and enhanced resistance to fatigue during repeated bouts of high-intensity contractions. PMID- 20591627 TI - More evidence to support the role of S2 in P50 studies. PMID- 20591626 TI - Patent foramen ovale and stroke. AB - The presence of a patent foramen ovale has been found to be associated with an increased risk of ischemic stroke of otherwise unknown origin (cryptogenic stroke). The present article will review the evidence regarding this association, the technical aspects of PFO detection, and the preventive options to decrease the risk of recurrent cerebral events. PMID- 20591628 TI - Polymorphisms of the LEP- and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin. AB - BACKGROUND: The role of leptin in atypical antipsychotic-induced metabolic dysfunction was explored by assessing the anthropometric and metabolic profile and the response to metformin (MET) of clozapine- (CLZ) treated schizophrenia patients according to their single nucleotide polymorphisms (SNPs) in the leptin promoter (LEP2548/GA) and leptin receptor (LEPR Q223R) genes. METHODS: Phase 1. Body mass index (BMI), waist circumference, serum glucose, HbA1C, lipids, leptin, cortisol, insulin resistance index (HOMA-IR), metabolic syndrome and the frequencies of SNPs were assessed in 56 CLZ-treated patients (78.6% males). Phase 2. Fifty two phase 1 subjects were randomly assigned to MET XR (n=23) (1000 mg/day) or placebo (n=29) for 14 weeks. Changes in anthropometric and biochemical variables were compared between the SNPs. RESULTS: Phase 1. The QQ group displayed the lowest triglyceride levels (p<0.05). No other significant difference was observed. Phase 2. Change in anthropometric variables did not differ between the genotypes in any treatment group. After MET, glucose levels significantly increased in the GG group (p<0.05), whereas the HOMA-IR and the low density cholesterol significantly decreased in the QQ- but not in the (QR+RR) group (p<0.05). No differences were observed after placebo. CONCLUSIONS: BW response to CLZ was not related to LEP- and LEPR-SNPs. The GG and (QR+RR) genotypes showed an unexpectedly opposite and blunted response to MET administration respectively. PMID- 20591629 TI - Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future. AB - The appearance of multiresistant bacterial strains coupled with the globally ongoing problem of infectious diseases point to the imperative need for novel and affordable antimicrobial drugs. The antibacterial potential of cardiovascular non antibiotics such as amlodipine (AML), dobutamine, lacidipine, nifedipine and oxyfedrine has been reported previously. Of these drugs, AML proved to have the most significant antibacterial activity against Gram-positive and Gram-negative bacteria. Time-kill curve studies indicate that this Ca(2+) channel blocker exhibits bactericidal activity against Listeria monocytogenes and Staphylococcus aureus. AML could protect against murine listeriosis and salmonellosis at doses ranging within its maximum recommended human or non-toxic ex vivo dose. AML acts as a 'helper compound' in synergistic combination with streptomycin against several Gram-positive and Gram-negative bacterial strains in vitro as well as in the murine salmonellosis model in vivo. The present review focuses on the possible use of cardiovascular non-antibiotics such as AML as auxiliary compound targets for synergistic combinations in infections and hypertension conditions, rationalised on the basis of the activities of the compounds. PMID- 20591630 TI - [BCG vaccination coverage in children born after the end of compulsory BCG vaccination and followed in maternal and child health clinics in France: a national survey 2009]. AB - OBJECTIVES: Compulsory BCG vaccination was replaced in July 2007 by a strong recommendation to vaccinate children at high risk of tuberculosis. We measured BCG vaccination coverage (VC) in children for whom BCG is recommended, who were born after the end of compulsory BCG vaccination and are usually followed at Maternal and Child Health Clinics (MCHC). METHODS: National sampling survey stratified by region and age group. Sample size was calculated in order to perform a separate analysis in Ile-de-France, region which has a specific vaccination policy and the highest tuberculosis incidence in mainland France. Children were selected through 2-stage random sampling in IDF and 3-stage random sampling outside IDF. They were recruited at the MCHC during the consultation where information was collected by the doctor through a structured questionnaire. RESULTS: BCG-VC was 89.8% (81.4-94.7) in IDF and 61.7% (53.8-69.0) outside IDF. In IDF, VC in children who had other criteria than solely residing in IDF was 92.4%. Outside IDF, children were on average vaccinated later than in IDF (i.e.: VC at the age of 3 months in children aged 2-12 months: 84% in IDF, 42% outside IDF). In both zones, children aged 2-12 months were vaccinated earlier compared to those aged >12 months. CONCLUSIONS: VC are high in children followed at MCHC in IDF, but can still be improved. They are insufficient in those followed at MCHC outside IDF where children are vaccinated too late. Efforts aimed at improving the dissemination of BCG vaccination recommendations and a better training of doctors in performing intradermal BCG vaccination could facilitate the implementation of this new BCG vaccination policy. PMID- 20591631 TI - [The out-of-home care of HIV-infected children]. AB - OBJECTIVE: To improve the conditions of out-of-home care of HIV-infected children. METHODS: Group discussions including staff members of 28 institutions having cared for an HIV-infected child with the objective to share 4 points of view: those of the HIV-infected child, of his parents, of the medical staff and of the out-of-home care professionals. RESULTS: Care professionals are uncomfortable with the confidentiality surrounding the diagnosis. The feeling of better controlling the risks justifies their wish to obtain medical information, although these risks are ill-defined. The contributions of the parents of HIV infected children shed a light on the link between the disclosure of the child's diagnosis and their intimacy and family history. Role-playing games with constructed scenarios revealed fixed and absurd aspects of certain beliefs and the difficulties to put in practice the acquired knowledge. The legitimacy of desire of parenthood in HIV-infected adults was questioned by some of the care professionals and their social representation of the person living with HIV appeared ambiguous, reminding the stigma these families are still victims of. CONCLUSION: Improving the conditions of out-of-home care of HIV-infected children requires ethical, legal and scientific counseling and discussions in the setting that should occur independently of the presence of a child with HIV. The disclosure of the diagnosis should only occur, if necessary, for their well being, with their or their parents' agreement. PMID- 20591632 TI - Validation of recursive partitioning analysis classification in patients with brain metastases from non-small cell lung cancer treated with short-course accelerated radiotherapy. AB - AIMS: To study various prognostic factors affecting outcome and to validate Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class in non-small cell lung cancer (NSCLC) with brain metastases treated with short course accelerated radiotherapy (SCAR). MATERIALS AND METHODS: The case records of 100 patients with NSCLC consecutively treated at Tata Memorial Hospital from August 2006 to August 2009 were studied for various patient, tumour and treatment related prognostic factors. Patients received whole-brain radiotherapy to a dose of 20 Gy/five fractions over 1 week (n=90) or 30 Gy/10 fractions over 2 weeks (n=10). The Kaplan-Meier estimate was used for survival analysis in SPSS v15. RESULTS: The median overall survival was 4.0 months (range 0.5-30.0 months). The 6-, 12-, 18- and 24-month survival rates were 35.8, 18.0, 9.3 and 6.2%, respectively. Of the various prognostic factors, RPA class (II versus III, P value=0.023), Karnofsky performance score (<70 versus >=70, P value=0.039) and the use of systemic therapy (yes versus no, P value=0.00) emerged as significant on univariate analysis. RPA classification effectively separated the patient population into prognostically distinct subgroups. The median overall survival for RPA class II and RPA class III was 6 and 4 months, respectively. The use of systemic therapy prolonged overall survival by 6 months (3 months versus 9 months). CONCLUSION: The SCAR regimen is an effective and resource-sparing palliative strategy for brain metastases in NSCLC. The results validate the usefulness of RPA classification in this specific subset of patients treated with SCAR. PMID- 20591633 TI - Prognostic significance of age in the radical treatment of oesophageal cancer with surgery or chemoradiotherapy: a prospective observational cohort study. AB - AIMS: To compare the outcomes of stage-directed surgical therapy and chemoradiotherapy (CRT) for oesophageal cancer and to determine if a significant age-treatment interaction exists to guide therapy. MATERIALS AND METHODS: Five hundred and eight consecutive patients with oesophageal cancer suitable for radical treatment based on radiological stage and performance status were studied (275 surgery; 93 surgery alone, 131 neoadjuvant chemotherapy, 51 neoadjuvant CRT and 233 definitive CRT). The primary measure of outcome was survival. RESULTS: Thirty-day mortality rates and 2-year survival after surgery and CRT in patients<70 years were 2.4 and 57.5%, respectively, compared with 0 (P=0.207) and 47.3% (P=0.011), respectively. Thirty-day mortality rates and 2-year survival after surgery and CRT in patients>or=70 years were 7.0 and 45.1%, respectively, compared with 0 (P=0.029) and 46.3% (P=0.992), respectively. Multivariate analysis including only surgical patients in the model revealed three factors to be independently and significantly associated with survival; endoscopic ultrasound (EUS) T stage (P=0.033), EUS lymph node metastasis count (>or=2 versus 0: hazard ratio 1.67, 95% confidence interval 1.06-2.92, P=0.026), and age>or=70 years (hazard ratio 1.51, 95% confidence interval 1.05-2.16, P=0.025). CONCLUSION: Overall survival for patients treated with surgery was strongly age dependent around the age of 70 years, and patients>or=70 years with oesophageal cancer should be aware that outcomes after CRT are similar to those after surgery. PMID- 20591634 TI - Coronary artery disease: clinical presentation, diagnosis and prognosis in women. AB - Recent advances in the field of cardiovascular medicine have not led to significant declines in case-fatality rates for women as in men. There are gender specific differences in symptoms profile, diagnosis and treatment of coronary disease in women. For women presenting for coronary heart disease (CHD) evaluation, traditional disease management approaches that focus on detection of a 'critical stenosis' often fail to identify those women critically at-risk. Symptoms do not help physicians in differential diagnosis of chest pain in women; indeed the most common presentation of obstructive CHD in women is atypical symptoms. In 50% of the cases, non-obstructive CHD at coronary angiography, due to 'noncardiac chest pain' or coronary microvascular dysfunction is frequently reported. For these reasons, the evidence reviewed suggests that prognostic risk assessment may work relatively better than diagnostic obstructive coronary disease assessment for women. PMID- 20591635 TI - Epidemiology of cardiovascular disease in Asian women. AB - This article presents data on CVD and risk factors in Asian women. Data were obtained from available cohort studies and statistics for mortality from the World Health Organization. CVD is becoming an important public health problem among Asian women. There are high rates of CHD mortality in Indian and Central Asian women; rates are low in southeast and east Asia. Chinese and Indian women have very high rates and mortality from stroke; stroke is also high in central Asian and Japanese women. Hypertension and type 2 DM are as prevalent as in western women, but rates of obesity and smoking are less common. Lifestyle interventions aimed at prevention are needed in all areas. PMID- 20591636 TI - Percutaneous revascularization in women with coronary artery disease: we've come so far, yet have so far to go. AB - Coronary artery disease (CAD) has traditionally been thought of as a disease that predominantly affects men. Women, however, are more likely than men to die from a myocardial infarction (MI). In this article, the data on access to cardiovascular care, treatment of stable and unstable coronary disease, and outcomes in women undergoing percutaneous coronary intervention (PCI) will be reviewed. Despite increased awareness of heart disease in women, and improved outcomes after PCI, women with MI have more mortality and delays to treatment than men. Women with CAD have symptoms that differ from men with CAD. Improved understanding of the symptoms of CAD in women by patients and health care providers may improve treatment and outcomes in women with CAD. PMID- 20591637 TI - Semi-automated quantitative image analysis of podocyte desmin immunoreactivity as a sensitive marker for acute glomerular damage in the rat puromycin aminonucleoside nephrosis (PAN) model. AB - Glomerular visceral epithelial cells or podocytes are crucial for glomerular function and podocyte damage has been shown to be inevitably involved in glomerulopathies. Podocytes react to injury in a stereotypic manner. Accompanying morphologic changes is altered expression of intermediate filaments. Desmin is strongly upregulated in injured podocytes. Here we show, that semi-automated quantitative image analysis of desmin immunoreactivity in glomerula is a valid and sensitive marker for acute podocyte and thus glomerular damage in the puromycin aminonucleoside nephrosis (PAN) model in the rat with the potential of an efficacy marker in animal disease models as well as a toxicity marker for podocyte injury. Additionally, a panel of acknowledged urinary kidney biomarkers was evaluated for utility in the PAN model. PMID- 20591638 TI - Development dependent collagen gene expression in the rat cranial base growth plate. AB - The spheno-occipital synchondrosis is part of the cranial base growth plate and is of crucial importance in craniofacial development. In this investigation, we studied changes in collagen gene expression in the spheno-occipital synchondrosis in order to identify the developmental stages most important for extracellular matrix production and ossification of the rat cranial base growth plate. Gene transcripts of type II and X collagen were most abundant at day 10 postnatally in the spheno-occipital synchondrosis. This observation is assumed to be due to intrinsic genetic factors and local environmental factors. PMID- 20591639 TI - Size, ultrastructure, and microhardness of natal teeth with agenesis of permanent successors. AB - OBJECTIVE: Natal and neonatal teeth may occur in conjunction with other oral anomalies, including anomalous development of succedaneous teeth. Our purpose was to examine the size, ultrastructure, and microhardness of two natal teeth without permanent successor germs, and compare them with the characteristics of normal primary teeth. DESIGN: The dimensions of two natal mandibular incisors extracted from a healthy 7-year-old child were measured with a digital sliding caliper. The crown dimensions of normal primary mandibular central incisors were established from dental casts of 102 children. Since the natal teeth were nearly completely devoid of enamel, the average enamel thickness determined on a sample of 19 normal primary mandibular incisors was added to the values measured. External surfaces and transverse sections of the natal teeth were examined under a scanning electron microscope. Vickers microhardness of radicular dentine was assessed for the natal teeth and for 11 normal primary mandibular incisors. RESULTS: Only remnants of enamel were present. All crown dimensions corrected for enamel loss were within the normal range. The ultrastructure of hard dental tissues was normal. The radicular dentine hardness of the natal teeth was similar to that of the normal primary mandibular incisors. CONCLUSIONS: The results indicate that the natal teeth were prematurely erupted regular primary mandibular central incisors. In our case, the occurrence of natal teeth associated with agenesis of their primary successors appears to be related to an accelerated or premature pattern of dental development, rather than to superficial positioning of the tooth germs. PMID- 20591640 TI - Morphological characterization of periodontium-derived human stem cells. AB - The aim of this study has been to characterize adult human somatic periodontium derived stem cells (PDSCS) isolated from human periodontium and to follow their differentiation after cell culture. PDSCS were isolated from human periodontal tissue and cultured as spheres in serum-free medium. After 10 days the primary spheres were dissociated and the secondary spheres sub-cultured for another 1-2 weeks. Cells from different time points were analyzed, and immunohistochemical and electron microscopic investigations carried out. Histological analysis showed differentiation of spheres deriving from the PDSCS with central production of extracellular matrix beginning 3 days after sub-culturing. Isolated PDSCS developed pseudopodia which contained actin. Tubulin was found in the central portion of the cells. Pseudopodia between different cells anastomosed, indicating intercellular transport. Immunostaining for osteopontin demonstrated a positive reaction in primary spheres and within extracellular matrix vesicles after sub culturing. In cell culture under serum-free conditions human PDSCS form spheres which are capable of producing extracellular matrix. Further investigations have do be carried out to investigate the capability of these cells to differentiate into osteogenic progenitor cells. PMID- 20591641 TI - Relevance of human anatomy in daily clinical practice. AB - AIM: the aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). MATERIALS AND METHODS: a total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. RESULTS: the response rate was 42.9% (n=536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. CONCLUSION: our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals. PMID- 20591643 TI - Influence of oxygen flow rate on reaction rate of organic matter in leachate from aerated waste layer containing mainly incineration ash. AB - It is known that aeration reduces rapidly the concentration of organic matter in leachate. However, the oxygen flow rate required to attain a certain reaction rate of organic matter should be carefully estimated. In this study, using the oxygen ratio (the ratio of oxygen flow rate by aeration to oxygen consumption rate of waste layer) as a parameter, the reaction rate of organic matter in leachate from landfilled incineration ash and incombustible waste upon aeration was evaluated. Total organic carbon (TOC) in the leachate was reduced rapidly when the oxygen ratio was high. The decomposition rate exceeded the elution rate of TOC in the leachate from the waste layer for several days when the oxygen ratio was above 10(2). The results indicate that the oxygen ratio can be used as a parameter for the aeration operation in actual landfill sites, to rapidly stabilize organic matter in leachate. PMID- 20591642 TI - Metabolic syndrome, hormones, and maintenance of T cells during aging. AB - Although the phenotype of T-cell senescence has been extensively investigated, few studies have analyzed the factors that promote the generation and maintenance of naive and memory T cells that exist throughout the lifespan of the individuals. Unlike senescent T cells, naive and memory T cells are able to participate in useful immune responses as well as respond to new activation. Hormones such as leptin, ghrelin, insulin-like growth factor 1, IGFBP3, and cytokines, including IL-7, regulate both thymopoiesis and maintenance of naive T cells in the periphery. Although chronic viruses such as cytomegalovirus (CMV) are thought to drive T-cell senescence, other microbes may be important for the maintenance of nonsenescent T cells. Microbiota of the gut can induce metabolic syndrome as well as modulate T-cell development into specific subpopulations of effector cells. Finally, T-cell generation, maintenance, and apoptosis depend upon pathways of energy utilization within the T cells, which parallel those that regulate overall metabolism. Therefore, better understanding of metabolic syndrome, T-cell metabolism, hormones, and microbiota may lead to new insights into the maintenance of proper immune responses in old age. PMID- 20591644 TI - A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoring. AB - Herewith we developed a novel 3D in vitro Alzheimer's disease (AD) model, based on the human neuroblastoma cell line SH-SY5Y, which is well differentiated without the application of any agents. Furthermore AD-like pathological neurodegeneration can be induced by okadaic acid (OA) mediated hyperphosphorylation of the microtubule associated protein tau. Moreover, we established stable "rapid tauopathy cell lines" expressing additional EGFP-fused (enhanced green fluorescent protein) wildtype or a pathology-promoting mutant tau variant (P301L) by lentiviral transduction. For the sensitive and feasible quantitative detection of pathological effects on neuronal 3D-cultures by electrochemical impedance spectroscopy (EIS) we optimized and redesigned a microcavity array (MCA). The cellular contribution to impedance could be increased by the factor of 2.5 and the variance decreased by 40%. Using our optimized MCA and impedance measurement setup we were able to detect quantitatively an OA concentration- and time-dependent decrease of the impedance in 3D SH-SY5Y cultures. Moreover, we were able to detect and quantify distinct, AD-related effects triggered by tau-mutant (P301L) expression and hyperphosphorylation in our organotypic 3D-cultures with the help of impedance spectroscopy. PMID- 20591645 TI - A simple electrochemical lectin-probe for in situ homogeneous cytosensing and facile evaluation of cell surface glycan. AB - This work constructed a novel electrochemical lectin-probe, ferrocene concanavalin A (Fc-ConA), for in situ monitoring of cell surface glycan by incorporating the specific recognition ability of lectin to glycan and favorable electrochemical property of ferrocenyl group. The covalent conjugation of ConA with ferrocenyl group was achieved by a carbodiimide coupling reaction and proved with UV-vis absorption spectroscopy and infrared spectroscopy. Cyclic voltammetric behavior of Fc-ConA at glassy carbon electrode demonstrated a reversible diffusion-controlled process. A facile homogeneous cytosensing strategy was then developed using Fc-ConA probe for detection of K562 cells. The suspending cells specifically captured Fc-ConA via membrane mannosyl groups and decreased the concentration of free Fc-ConA, producing a response correlative with cell number and the content of cell surface glycan. A wide linear response to cells ranging from 1 * 10(4) to 1 * 10(7) cells mL(-1) with a calculated detection limit of 3000 cells mL(-1) was obtained. The lectin-probe could be conveniently used to in situ evaluate cell surface glycan. The average number of mannose moieties on single living K562 cell was detected to be 3.0 * 10(10), while this value increased by 81% on drug-treated cells. These results agreed with those from flow cytometric detection. This strategy presented a promising platform for homogeneous sensitive cytosensing and facile monitoring of carbohydrate expression on living cells in response to drugs. PMID- 20591646 TI - The roles of PARP1 in gene control and cell differentiation. AB - Cell growth and differentiation during developmental processes require the activation of many inducible genes. However, eukaryotic chromatin, which consists of DNA and histones, becomes a natural barrier impeding access to the functional transcription machinery. To break through the chromatin barrier, eukaryotic organisms have evolved the strategy of using poly(ADP-ribose) polymerase 1 (PARP1) to modulate chromatin structure and initiate the steps leading to gene expression control. As a structural protein in chromatin, enzymatically silent PARP1 inhibits transcription by contributing to the condensation of chromatin, which creates a barrier against gene transcription. However, once activated by environmental stimuli and developmental signals, PARP1 can modify itself and other chromatin-associated proteins, thereby loosening chromatin to facilitate gene transcription. Here we discuss the roles of PARP1 in transcriptional control during development. PMID- 20591647 TI - The FoxA factors in organogenesis and differentiation. AB - The genetic analysis of the Foxa genes in both total and conditional mutant mice has clearly established that organogenesis of multiple systems is controlled by this subfamily of winged helix transcription factors. These discoveries followed the establishment of the conceptional framework of the mechanism of action of the FoxA proteins as 'pioneer factors' that can engage chromatin before other transcription factors. Recent molecular and genomic studies have also shown that FoxA proteins can facilitate binding of several nuclear receptors to their respective targets in a context-dependent manner, greatly increasing the range and importance of FoxA factors in biology. PMID- 20591648 TI - Protein engineering for bioenergy and biomass-based chemicals. AB - The conversion of biomass to fuels and chemicals faces substantial challenges if it is to be done on a large scale, in a sustainable manner, and at reasonable cost. Some of these challenges can be addressed through protein engineering technologies, for example by improving biomass-processing enzymes or by manipulating the activities and substrate specificity of enzymes in metabolic pathways. Recent highlights include structure-guided chimera design to improve the properties of cellulases, the engineering of synthetic scaffold proteins to enhance metabolic flux, and the broadening of substrate specificity to co-opt metabolic pathways to the production of long-chain branched alcohols. PMID- 20591649 TI - Proteins that switch folds. AB - An increasing number of proteins demonstrate the ability to switch between very different fold topologies, expanding their functional utility through new binding interactions. Recent examples of fold switching from naturally occurring and designed systems have a number of common features: (i) The structural transitions require states with diminished stability; (ii) Switching involves flexible regions in one conformer or the other; (iii) A new binding surface is revealed in the alternate fold that can lead to both stabilization of the alternative state and expansion of biological function. Fold switching not only provides insight into how new folds evolve, but also indicates that an amino acid sequence has more information content than previously thought. A polypeptide chain can encode a stable fold while simultaneously hiding latent propensities for alternative states with novel functions. PMID- 20591650 TI - Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma. AB - Insulin-like growth factor 1 receptor (IGF-1R) is overexpressed in many tumours and contributes to tumourigenicity, cell proliferation, metastasis and resistance, thus representing a promising therapeutic target. The human IGF-1R antagonistic monoclonal antibody EM164 (murine AVE1642) has shown activity in adult cancers and is being evaluated in patients with advanced malignancies. We investigated the EM164 for its therapeutic potential against childhood neuroblastoma. EM164 at 0.07, 0.7 and 7 MUg/mL exhibited anti-proliferative activity against all nine cell lines tested in (3)H-thymidine incorporation assay in vitro. Cell proliferation after EM164 exposure ranged between 24% and 80% compared to controls. Sensitivity was independent from culture serum conditions, intensity of IGF-1R expression and IGF-II secretion, although associated with inhibition of AKT activation. In vivo, EM164 administered intravenously at 40 mg/kg twice weekly for 4 weeks yielded significant tumour growth delays (TGD) of 13.4d in advanced stage IGR-N91 and 12.9 d in SK-N-AS tumours compared to controls (p = 0.02 and p = 0.0059, respectively). Simultaneous treatment of EM164 0.7 MUg/mL and temozolomide resulted in enhanced activity in vitro. In vivo, treatment with temozolomide at the maximum tolerated dose (100mg/kg/d for 5 consecutive days) and EM164 yielded a significantly greater TGD of 29.1d (p<0.01) and two complete tumour regressions (CR) compared to 18.1d (p = ns) and one CR for EM164 alone and 16.1d (p = ns) for temozolomide alone. Our results demonstrate the potential of the anti-IGF-1R antibody alone and in combination with alkylating agents and support the therapeutic development of the AVE1642 for aggressive neuroblastoma. PMID- 20591651 TI - HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53/p73 dependent manner in neuroblastoma. AB - HDM2, a human homologue of MDM2, is a major negative regulator of p53 function, and increased expression of HDM2 by its promoter polymorphism SNP309 resulted in p53 inactivation and an increased risk of several tumours, including neuroblastoma (NB). Herein, we show that increased expression of HDM2 is related to a worse prognosis in MYCN-amplified NB patients. HDM2 plays an important role in the expression of Noxa, a pro-apoptotic molecule of the Bcl-2 family, which induces NB cell apoptotic death after doxorubcin (Doxo) treatment. Knockdown of HDM2 by siRNA resulted in the upregulation of Noxa at mRNA/protein levels and improved the sensitivity of Doxo-resistant NB cells, although these were not observed in p53-mutant NB cells. Noxa-knockdown abolished the recovered Doxo induced cell death by HDM2 reduction. Intriguingly, resistance to Doxo was up regulated by over-expression of HDM2 in Doxo-sensitive NB cells. By HDM2 expression, p53 was inactivated but its degradation was not accelerated, suggesting that p53 was degraded in a proteasome-independent manner in NB cells; downstream effectors of p53, p21(Cip1/Waf1) and Noxa were suppressed by HDM2. Noxa transcription was considerably regulated by both p53 and p73 in NB cells. Furthermore, in vivo binding of p53 and p73 to Noxa promoter was suppressed and Noxa promoter activation was inhibited by HDM2. Taken together, our results may indicate that the HDM2-related resistance to chemotherapeutic drugs of NB is regulated by p53/p73-dependent Noxa expression in NB. PMID- 20591652 TI - Adsorption kinetics of chromium(III) ions on agro-waste materials. AB - The objective of this research is to compare empirical (pseudo-first and pseudo second order models) and diffusional models (film diffusion, film-pore-volume diffusion, and film-surface diffusion models) in predicting the adsorption kinetics of chromium(III) on water-washed agro-waste materials (sorghum straw, oats straw, and agave bagasse). Concentration decay curves can be predicted by using either empirical or diffusional kinetic models. However, the film diffusion model seems to be the most appropriated one based on the low reported deviation (0.45-4.09%), and the physical properties (low porosity 0.004-0.007, low surface area 0.6-1.2m(2)g(-1) and low pore volume 0.003-0.004cm(3)g(-1)) of the studied agro-waste materials, which support the idea that intraparticle diffusion may be neglected. Furthermore, the external mass transfer coefficient estimated with the film diffusion model has a physical meaning that helps to explain the diffusion of solutes across the film resistance in agro-waste biosorbents. PMID- 20591653 TI - Biosynthesis of medium-chain-length poly(3-hydroxyalkanoates) by volatile aromatic hydrocarbons-degrading Pseudomonas fulva TY16. AB - Pseudomonas fulva TY16 biosynthesized medium-chain-length poly(3 hydroxyalkanoates) (MCL-PHAs) containing unsaturated 3-hydroxydodecenoate unit (approximately 8-9%) when grown with volatile aromatic compounds including benzene, toluene, and ethylbenzene as sole carbon substrate. In particular, when cultivated using a continuous feeding system designed to supply toluene at a flow rate of 0.42gL(-1)h(-1) into a 7-L jar fermentor, the growth of the organism reached up to approximately 3.87gL(-1) after the 48h fed-batch fermentation, representing an accumulated cellular MCL-PHA of 58.9% by weight. The obtained MCL PHA was a copolyester primarily consisting of 3-hydroxydecanoate (55.2%) and 3 hydroxyoctanoate (26.8%) with minor constituents being 3-hydroxyhexanoate (3.7%), 3-hydroxydodecenoate (8.2%), and 3-hydroxydodecanoate (6.1%). The present results suggest that P. fulva TY16 is a promising candidate for the biotechnological conversion of toxic petrochemical wastes to valuable biopolymers. PMID- 20591654 TI - Microbial production of acetoacetate by recombinant Escherichia coli. AB - A synthetic pathway consisting of octAB encoding succinyl-CoA:acetoacetate CoA transferase and phaA encoding beta-ketothiolase from Ralstonia eutropha H16 was constructed in Escherichia coli for extracellular production of acetoacetate. The recombinant E. coli produced 8.2g/l acetoacetate in shake flasks at 37 degrees C in 24h. In a 6-L fermentor, extracellular acetoacetate production was enhanced to 13.1g/l after 30h of fed-batch growth. To our knowledge, this is the first study on microbial production of acetoacetate. PMID- 20591655 TI - Optimization of direct conversion of wet algae to biodiesel under supercritical methanol conditions. AB - This study demonstrated a one-step process for direct liquefaction and conversion of wet algal biomass containing about 90% of water to biodiesel under supercritical methanol conditions. This one-step process enables simultaneous extraction and transesterification of wet algal biomass. The process conditions are milder than those required for pyrolysis and prevent the formation of by products. In the proposed process, fatty acid methyl esters (FAMEs) can be produced from polar phospholipids, free fatty acids, and triglycerides. A response surface methodology (RSM) was used to analyze the influence of the three process variables, namely, the wet algae to methanol (wt./vol.) ratio, the reaction temperature, and the reaction time, on the FAMEs conversion. Algal biodiesel samples were analyzed by ATR-FTIR and GC-MS. Based on the experimental analysis and RSM study, optimal conditions for this process are reported as: wet algae to methanol (wt./vol.) ratio of around 1:9, reaction temperature and time of about 255 degrees C, and 25 min respectively. This single-step process can potentially be an energy efficient and economical route for algal biodiesel production. PMID- 20591656 TI - Identification of two flavin monooxygenases from an effluent treatment plant sludge metagenomic library. AB - Oxygenases are useful for the production of many industrially important molecules. Screening of an effluent treatment plant (ETP) sludge metagenomic library identified two clones encoding proteins, B1 and B2, with similarity to putative flavin monooxygenases from Mesorhizobium loti and Sphingomonas wittichi, respectively. The deduced amino acid sequences show only 20% identity, but both have a paired Rossman fold and a flavin monooxygenase (FMO) motif. B1 and B2 appear to be members of the flavin-containing monooxygenase and the Baeyer Villiger monooxygenases subfamilies, respectively. When expressed in Escherichia coli, the two clones produced activities that oxidized indole to a mixture of indigo and indirubin pigments. These results suggest that B1 and B2 have potential as a biocatalyst in indigo/indirubin production. PMID- 20591657 TI - Differential lipid and fatty acid profiles of photoautotrophic and heterotrophic Chlorella zofingiensis: assessment of algal oils for biodiesel production. AB - The objective of this study was to document and compare the lipid class and fatty acid composition of the green microalga Chlorella zofingiensis cultivated under photoautotrophic and heterotrophic conditions. Compared with photoautotrophic cells, a 900% increase in lipid yield was achieved in heterotrophic cells fed with 30 g L(-1) of glucose. Furthermore heterotrophic cells accumulated predominantly neutral lipids (NL) that accounted for 79.5% of total lipids with 88.7% being triacylglycerol (TAG); whereas photoautotrophic cells contained mainly the membrane lipids glycolipids (GL) and phospholipids (PL). Together with the much higher content of oleic acid (C18:1) (35.2% of total fatty acids), oils from heterotrophic C. zofingiensis appear to be more feasible for biodiesel production. Our study highlights the possibility of using heterotrophic algae for producing high quality biodiesel. PMID- 20591658 TI - Optimization of poly-epsilon-lysine production by Streptomyces noursei NRRL 5126. AB - Poly-epsilon-lysine (epsilon-PL) is a non-toxic biopolymer with antimicrobial properties. The production of epsilon-PL by Streptomyces noursei NRRL 5126 shake flask culture was optimized by identifying the most significant medium components which affect epsilon-PL production (glycerol, proteose peptone and ammonium sulphate) by Placket-Burman design and by application of an evolutionary operation (EVOP) to determine the optimal concentrations of these components. The epsilon-PL yield increased from 41.81 g/l in basal medium to 98.07 g/l in the EVOP-optimized medium containing 3% glycerol, 1% proteose peptone and 0.8% ammonium sulphate. Further improvements in media composition and culture conditions will be required to obtain yields comparable to those obtained with current commercial strains such as Streptomyces albulus. PMID- 20591659 TI - Time-course correlation of biofilm properties and electrochemical performance in single-chamber microbial fuel cells. AB - The relationship between anode microbial characteristics and electrochemical parameters in microbial fuel cells (MFCs) was analyzed by time-course sampling of parallel single-bottle MFCs operated under identical conditions. While voltage stabilized within 4days, anode biofilms continued growing during the six-week operation. Viable cell density increased asymptotically, but membrane-compromised cells accumulated steadily from only 9% of total cells on day 3 to 52% at 6weeks. Electrochemical performance followed the viable cell trend, with a positive correlation for power density and an inverse correlation for anode charge transfer resistance. The biofilm architecture shifted from rod-shaped, dispersed cells to more filamentous structures, with the continuous detection of Geobacter sulfurreducens-like 16S rRNA fragments throughout operation and the emergence of a community member related to a known phenazine-producing Pseudomonas species. A drop in cathode open circuit potential between weeks two and three suggested that uncontrolled biofilm growth on the cathode deleteriously affects system performance. PMID- 20591660 TI - A novel strategy for integrated utilization of Jerusalem artichoke stalk and tuber for production of 2,3-butanediol by Klebsiella pneumoniae. AB - Jerusalem artichoke stalk and tuber can serve as a low cost feedstock for the production of 2,3-butanediol. However, like other lignocellulosic materials, the sugar concentration in the hydrolysate prepared from Jerusalem artichoke stalk is too low to be utilized effectively by microorganisms. In this paper a novel strategy was proposed to increase the sugar concentration by adding Jerusalem artichoke tuber into the hydrolysate of the stalk. The sugar was then biotransformed into high-valued 2,3-butanediol by Klebsiella pneumoniae. Fed batch simultaneous saccharification and fermentation (SSF) was effectively performed and 901.2 mmol/l (80.5 g/l) target products (2,3-butanediol plus acetoin) was obtained in 68 h by a stage-shift aeration strategy. The concentration, yield and productivity of target products were 16.9%, 16.8% and 23.4%, respectively, higher than the best results obtained with SSF operated under constant aeration. This showed that adding tuber to the stalk hydrolysate was a useful strategy for increasing the production of 2,3-butanediol from Jerusalem artichoke via fermentation. PMID- 20591661 TI - An alpha-galactosidase from an acidophilic Bispora sp. MEY-1 strain acts synergistically with beta-mannanase. AB - An alpha-galactosidase gene (AgalB) was cloned from the acidophilic fungus Bispora sp. MEY-1 and expressed in Pichia pastoris. The deduced amino acid sequence showed highest identity (35%) to the alpha-galactosidase from Penicillium simplicissimum, belonging to the glycosyl hydrolase family 27. The purified recombinant alpha-galactosidase (r-AgalB) exhibited optimal activity at pH 3.5 and 55 degrees C, was stable at pH 2.2-8.0, and showed higher hydrolytic activity towards galactomannan polysaccharides (guar gum and locust bean gum) than toward small galacto-oligosaccharides (melibiose, raffinose and stachyose). A synergistic (3-fold) increase in guar gum hydrolysis was observed when beta mannanase Man5A from Bispora sp. MEY-1 and r-AgalB were combined. Further, an increase in the reaction time from 5h to 12h or increase of the temperature from 37 degrees C to 55 degrees C enhanced guar gum degradation by the enzyme combination. These properties make r-AgalB a good candidate for extensive application in the pulp/paper, food, and feed industries. PMID- 20591662 TI - Kinetics of transesterification of palm oil and dimethyl carbonate for biodiesel production at the catalysis of heterogeneous base catalyst. AB - The transesterification of palm oil with dimethyl carbonate (DMC) for preparing biodiesel has been studied in solvent-free system at the catalysis of potassium hydroxide (KOH) as heterogeneous catalyst. Fatty acid methyl esters (FAMEs) were analyzed by GC with internal standard method. The effects of reaction conditions (molar ratio of DMC and palm oil, catalyst amount and time) on FAMEs yield were investigated. The highest FAMEs yield could reach 96.2% at refluxing temperature for 8h with molar ratio of DMC and oil 9:1 and 8.5% KOH (based on oil weight). Kinetics of the KOH-catalyzed transesterification of palm oil and DMC was researched over a temperature range of 65-75 degrees C. A pseudo first-order model was proposed. The activation energy (E(a)) was 79.1 kJ mo1(-1) and the pre exponential factor (k(o)) was 1.26 x 10(9) min(-1) from Arrhenius equation. Further, a plausible reaction mechanism for the catalytic process with DMC as acyl acceptor was proposed. PMID- 20591663 TI - Identification of novel alpha7 nAChR positive allosteric modulators with the use of pharmacophore in silico screening methods. AB - The pharmacophore model of in house potent and selective alpha7 nAChR positive allosteric modulators is reported. The model was used to fish out commercially available compounds from corporate 3D databases. As a result, novel alpha7 positive modulator chemotypes were identified. A rat full PK profile of a representative compound is also described. PMID- 20591664 TI - Synthesis of 2-(4-substituted benzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3-oxo-2H benzo[b][1,4]oxazin-7-yl)acetamides and their positive inotropic evaluation. AB - Herein we describe the discovery of compound 3g, a potent positive inotropic agent compared with the standard drug, milrinone. Compound 3g was developed from a series of 2-(4-substitutedbenzyl-1,4-diazepan-1-yl)-N-(3,4-dihydro-3-oxo-2H benzo[b][1,4]oxazin-7-yl) acetamides found in an evaluation of inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activities, but 3g was the most potent, with 7.68+/-0.14% increased stroke volume (milrinone 2.38+/-0.05%) at 1 x 10(-5)M in our in vitro study. The chronotropic effects of compounds having significant inotropic effects were also evaluated. PMID- 20591665 TI - Synthesis and activity of polyacetylene substituted 2-hydroxy acids, esters, and amides against microbes of clinical importance. AB - A series of novel polyacetylene substituted 2-hydroxy acids and derivatives were prepared and characterized. Alkylation of butane-2,3-diacetal (BDA) protected glycolic acid with iodoalkyl substituted polyacetylene compounds gave the corresponding diacetal protected polyacetylene substituted 2-hydroxy acids. Diacetal deprotection through acid mediated hydrolysis, transesterification or aminolysis afforded the 2-hydroxy-polyacetylenic acid, ester or amide derivatives. Twenty one of these novel compounds were tested against 10 microbes of clinical importance and several of them showed good antimicrobial activity, in particular against Pseudomonas aeruginosa. PMID- 20591666 TI - A new group of oxime carbamates as reversible inhibitors of fatty acid amide hydrolase. AB - A series of oxime carbamates have been identified as potent inhibitors of fatty acid amide hydrolase (FAAH), an important regulatory enzyme of the endocannabinoid signaling system. Kinetic analysis indicates that they behave as non-competitive, reversible inhibitors, and show remarkable selectivity for FAAH over the other components of the endocannabinoid system. PMID- 20591667 TI - Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties. AB - The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an aqueous buffer and both phospholipids are hydrolyzed by phospholipase A(2), but with different conversion rates and extent of hydrolysis. The cytotoxicity was evaluated in HT 29 and Colo205 cells and the conjugates induced cell death in the presence of phospholipase A(2) and surprisingly also in the absence of the enzyme. PMID- 20591668 TI - In silico studies on the substrate specificity of an l-arabinose isomerase from Bacillus licheniformis. AB - l-Arabinose isomerase (BLAI) from Bacillus licheniformis was found to be active only with l-arabinose, unlike other l-arabinose isomerases (l-AIs) active with a variety of aldoses. Therefore, the differences in molecular interactions and substrate orientation in the active site of l-AIs have been examined and the residue at position 346 is proposed to be responsible for the unique substrate specificity of BLAI. PMID- 20591669 TI - In vivo and in vitro SAR of tetracyclic MAPKAP-K2 (MK2) inhibitors. Part II. AB - Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D-E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC(50)<3 nM and inhibit the release of TNFalpha (IC(50)<0.3 microM) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC(50)=0.05-0.23 microM), less potent in cells (IC(50)<1.1 microM), but show good oral absorption. Compound 13E (100mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. PMID- 20591670 TI - Why statin therapy may increase the risk for posttransplantation squamous cell carcinoma. AB - We suggest that surveillance for squamous cell cancer might be particularly useful for transplant patients receiving statin therapy. We recommend that development of non melanoma skin cancer should be specified as a secondary endpoint in future large endpoint statin trials, and suggest that in transplant patients the adverse effects of statin drugs may outweigh benefits, especially in women and the elderly, a subset of population in which even individuals at high risk for cardiovascular disease have shown no trend to net benefit from statins. PMID- 20591671 TI - Anterior cruciate ligament reconstruction results in alterations in gait variability. AB - INTRODUCTION: The temporal structure of gait variability has shown that healthy human gait exhibits long-range correlations and deterministic properties which allow the neuromuscular system to be flexible and adaptable to stresses. Pathology results in deterioration of these properties. We examined structure of gait variability after ACL reconstruction with either BPTB or quadrupled ST/G tendon autografts. METHODS: Six patients with BPTB reconstruction, six with ST/G reconstruction and six healthy controls walked on a treadmill at their self selected pace. Two minutes of continuous kinematic data were recorded with a 6 camera optoelectronic system. The nonlinear measure of the largest Lyapunov Exponent (LyE) was estimated from the knee flexion-extension time series from 100 continuous walking strides to assess the structure of gait variability. RESULTS: The reconstructed limbs in both reconstructed groups exhibited significantly larger LyE values than the control limbs (p<0.05), even though clinical outcomes indicated complete restoration. No significant differences were found between the two autografts. In addition, the intact contralateral leg produced significant higher LyE values as compared with the ACL-reconstructed leg in both groups. No interaction was found. DISCUSSION: The larger LyE values indicate that the reconstructed knees of both reconstructed groups exhibit more divergence in the movement trajectories during gait. The larger Lye values found in the intact leg in both reconstructed groups could be interpreted as a compensatory mechanism. However, the increased divergence found in both limbs may present an alternative explanation for the impaired neuromuscular performance and increased susceptibility to future pathology, which is supported by the increased amount of osteoarthritis found in ACL-reconstructed patients. PMID- 20591672 TI - A regression method for strength comparisons in children. AB - A method to estimate means and variance of strength based on anthropometric data is presented. The method is applied using a database of 10 lower extremity strength measures recorded from 48 typically developing children with a handheld dynamometer. Seven anthropometric variables are considered, and the combination of height and BMI is determined as a set of variables best suited to model these muscle groups. This regression scheme accounts for 45-58% of the observed variance. A clinical example illustrating the utility of the method is presented. PMID- 20591673 TI - Botulinum toxin injection of the subscapularis muscle. AB - Patients with hemiplegia frequently suffer from pain and have a limited range of motion (ROM) of the shoulder. The common pattern of shoulder movement in a patient with spastic hemiplegia is primarily adduction and internal rotation. Spasticity of the subscapularis muscle limits the abduction, external rotation and flexion of the shoulder. Injection of botulinum toxin or application of phenol can reduce the spasticity of the subscapularis muscle and various techniques to inject this muscle have been reported. We injected five patients with hemiplegia with botulinum toxin using our previously reported inferior approach, which is easy, safe and effective. We observed a reduction in pain and spasticity and improvement in the ROM of the shoulder for all patients. PMID- 20591674 TI - Post-partum pituitary apoplexy with bilateral third nerve palsy and bilateral carotid occlusion. AB - This study describes a patient with post-partum collapse secondary to pituitary apoplexy with bilateral carotid artery occlusion. A 29-year-old female, post delivery of a healthy child, presented with a Glasgow Coma Scale score of 3, fixed dilated pupils, complete ophthalmoplegia, and bilateral compression of the internal carotid arteries. These symptoms were due to a giant pituitary macroadenoma. She underwent a craniotomy and subsequently survived with minor cognitive deficits and functional vision. Bilateral carotid occlusion caused by pituitary apoplexy is rare, yet survival with only minor deficits is possible. PMID- 20591675 TI - Blood loss following total knee replacement in the morbidly obese: Effects of computer navigation. AB - Computer navigated total knee arthroplasty (TKA) has several proposed benefits including reduced post-operative blood loss. We compared the total blood volume loss in a cohort of morbidly obese (BMI>40) patients undergoing computer navigated (n=30) or standard intramedullary techniques (n=30) with a cohort of matched patients with a BMI<30 also undergoing navigated (n=31) or standard TKA (n=31). Total body blood loss was calculated from body weight, height and haemotocrit change, using a model which accurately assesses true blood loss as was maximum allowable blood loss which represents the volume of blood that can be lost until a transfusion trigger is required. The groups were matched for age, gender, diagnosis and operative technique. The mean true blood volume loss across all BMI's was significantly (p<0.001) less in the computer assisted group (1014+/ 312ml) compared to the conventional group (1287+/-330ml). Patients with a BMI>40 and a computer navigated procedure (1105+/-321ml) had a significantly lower (p<0.001) blood volume loss compared to those who underwent a conventional TKA (1399+/-330ml). There was no significant difference in the transfusion rate or those reaching the maximum allowable blood loss between groups. This study confirms a significant reduction in total body blood loss between computer assisted and conventional TKA in morbidly obese patients. However computer navigation did not affect the transfusion rate or those reaching the transfusion trigger in the morbidly obese group. Therefore computer navigation may reduce blood loss in the morbidly obese patient but this may not be clinically relevant to transfusion requirements as previously suggested. PMID- 20591676 TI - Treatment of chronic disruption of the patellar tendon in Osteogenesis Imperfecta with allograft reconstruction. AB - We present a case of chronic disruption of the patellar tendon in a patient with Osteogenesis Imperfecta. This patient was treated with a customized extensor mechanism allograft. Results were excellent at 5 years follow up. To our knowledge this treatment has not previously been published in this situation. We present this as a reliable treatment option. PMID- 20591677 TI - Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in Rabbit. AB - Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. Increasing incidence of OA and the aging population coupled with insufficient therapeutic choices has led to focus on the potential of stem cells as a novel strategy for cartilage repair. In this study, we used scaffold free mesenchymal stem cells obtained from infrapatellar fat pad in an experimental animal model of OA by direct intraarticular injection. Mesenchymal stem cells isolated from a 2.8kg White New Zealand rabbit. The cells were expanded and grown in vitro. OA was induced by unilaterally anterior cruciate ligament transection of knee joints. Twelve weeks after operation, a single dose of 1 million cells suspended in 1ml of medium was delivered to the injured knee by direct intraarticular injection. Control group received 1ml of medium without cells. The knees were examined after sixteen and twenty weeks from the surgery. Repairing was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving mesenchymal stem cells showed lower degree of cartilage degeneration, osteophyte formation, and Subchondral sclerosis than control group at 20 week after surgery. The quality of cartilage was significantly better in cell-treated group compared with control group after 20 weeks. In conclusion, infrapatellar fat pad derived mesenchymal stem cells could be the promising cell sources for the treatment of OA. PMID- 20591678 TI - Synthesis and antiproliferative evaluation of certain iminonaphtho[2,3-b]furan derivatives. AB - Certain iminonaphtho[2,3-b]furan derivatives were synthesized from their respective carbonyl precursors in the regiospecific and the stereospecific manners. These compounds were evaluated for their antiproliferative effects against four human carcinoma cells (MCF7, NCI-H460, SF-268, and K562) and the normal fibroblast cell line (Detroit 551). Among them, (Z)-4 (hydroxyimino)naphtho[2,3-b]furan-9(4H)-one (8) and (Z)-4-methoxy iminonaphtho[2,3-b]furan-9(4H)-one (9) exhibited GI(50) values of 0.82 and 0.60 microM, respectively, against the growth of K562 cells and were inactive against the normal fibroblast Detroit 551. The selectivity index (SI) on K562 cell for 8 and 9 was >121.95 and >166.67, respectively, which is comparable to daunorubicin (SI=239) and is more favorable than camptothecin (SI=16.5). The cell cycle analysis on K562 indicated that these compounds arrest the cell cycle at the G2/M phase. The morphological assessment and DNA fragmentation analysis indicated that 9-induced cell apoptosis in K562 cells. The apoptotic induction may through caspase-3 activity and cleavage of PARP. PMID- 20591679 TI - Development of chemical probes: toward the mode of action of a methylene-linked di(aryl acetate) E1. AB - Analogues of the novel inhibitor of the PI3-K/PKB pathway, 2-[5-(2-chloroethyl)-2 acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate (E1), have been prepared and preliminary SAR performed. This established that at least one of the chloroethyl para-substituents could be removed or modified and the ability to inhibit PKB/Akt activation retained. Synthetic methodologies were then developed to methylene linked aryl acetates for use as molecular probes to identify the target of compound E1. PMID- 20591680 TI - STD-NMR studies of two acceptor substrates of GlfT2, a galactofuranosyltransferase from Mycobacterium tuberculosis: epitope mapping studies. AB - The major structural component of the mycobacterial cell wall, the mycolyl arabinogalactan-peptidoglycan complex, possesses a galactan core composed of approximately 30 galactofuranosyl (Galf) resides attached via alternating beta-(1 ->6) and beta-(1-->5) linkages. Recent studies have shown that the entire galactan is synthesized by two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2. We report here saturation transfer difference (STD) NMR studies GlfT2 using two trisaccharide acceptor substrates, beta-D-Galf-(1-->6)-beta-D-Galf-(1- >5)-beta-D-Galf-O(CH2)7CH3 (2) and beta-D-Galf-(1-->5)-beta-D-Galf-(1-->6)-beta-D Galf-O(CH2)7CH3 (3), as well as the donor substrate for the enzyme, UDP-Galf. Epitope mapping demonstrated a greater enhancement toward the 'reducing' ends of both trisaccharides, and that UDP-galactofuranose (UDP-Galf) made more intimate contacts through its nucleotide moiety. This observation is consistent with the greater flexibility required within the active site of the reaction between the growing polymer acceptor and the UDP-Galf donor. The addition of UDP-Galf to either 2 or 3 in the presence of GlfT2 generated a tetrasaccharide product, indicating that the enzyme was catalytically active. PMID- 20591681 TI - Morphological characterization of the mouthparts of the vector leafhopper Psammotettix striatus (L.) (Hemiptera: Cicadellidae). AB - The leafhopper Psammotettix striatus (L.) (Hemiptera: Cicadellidae), is one of the most significant economic pests of wheat in Western China. This insect vectors a phytoplasma that causes wheat blue dwarf (WBD), a severe disease limiting wheat production in the Western China. A microscopic analysis of the ultrastructure of the mouthparts of the adult was conducted using scanning electron microscopy and the putative functions of the mouthparts were determined. The piercing-sucking mouthparts of P. striatus are of the conventional type comprising a three-segmented labium with a deep groove in the anterior side, a stylet fascicle consisting of two mandibular and two maxillary stylets, and an uppermost small cone-shaped labrum. The mandibular stylets, located laterad of the maxillary stylets, have sculpture on their tips, which may function in tearing plant tissue, cutting channels into the plant tissues, and attaching the body to the host plant during molting. The maxillary stylets are interlocked to form two separate compartments, a larger food canal and a smaller salivary canal. Two dendritic canals are also found in each maxilla and one in each mandible. Four kinds of sensilla were found on the labium: s. trichodea I, s. trichodea II, s. basiconic I, s. basiconic II. These may be involved in host recognition and are likely chemo- or mechanosensory, or both. PMID- 20591682 TI - Concomitant left and right coronary to bronchial artery fistulae resulting in myocardial ischaemia. PMID- 20591683 TI - Pre-conditioning with the soluble guanylate cyclase activator Cinaciguat reduces ischaemia-reperfusion injury after cardiopulmonary bypass. AB - OBJECTIVE: Activation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway can induce potent cardioprotection like effects against ischaemia-reperfusion injury and nitro-oxidative stress. We investigated the effects of pharmacological pre-conditioning with Cinaciguat (BAY 58-2667), a novel sGC activator on peroxynitrite-induced endothelial dysfunction in vitro, as well as on myocardial and coronary vascular function during reperfusion in a canine model of cardioplegic arrest and extracorporeal circulation. METHODS: Isolated coronary arterial rings exposed to peroxynitrite were investigated for vasomotor function. Vehicle- and Cinaciguat-pre-treated (8.33 MUg h(-1) or 25 MUg h(-1) intravenous (IV) for 30 min) anaesthetised dogs (n = 6-7 per group) underwent hypothermic cardiopulmonary bypass with 60 min of hypothermic cardioplegic arrest. Left- and right-ventricular end-systolic pressure-volume relationship (ESPVR) was measured by a pressure-volume conductance catheter at baseline and after 60 min of reperfusion. Coronary blood flow, vasodilatation to acetylcholine and myocardial level of adenosine triphosphate were determined. RESULTS: Pre-incubation of coronary rings with Cinaciguat improved peroxynitrite-induced endothelial dysfunction. Compared with control, pharmacological pre-conditioning with Cinaciguat (25 MUg h(-1)) led to higher myocardial adenosine triphosphate content, to a better recovery of left- and right-ventricular contractility (Delta slope of left ventricular ESPVR given as percent of baseline: 102.4 +/- 19.1% vs 56.0 +/- 7.1%) and to a higher coronary blood flow (49.6 +/- 3.5 ml min(-1) vs 28.0 +/- 3.9 ml min(-1)). Endothelium-dependent vasodilatation to acetylcholine was improved in the treatment groups. CONCLUSIONS: Pre-conditioning with Cinaciguat improves myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that pharmacological sGC activation could be a novel therapeutic option in the protection against ischaemia-reperfusion injury in cardiac surgery. PMID- 20591685 TI - The integrated place of tracheobronchial stents in the multidisciplinary management of large post-pneumonectomy fistulas: our experience using a novel customised conical self-expandable metallic stent. AB - BACKGROUND: Stump dehiscence after pneumonectomy is a cause of morbidity and mortality in patients treated for non-small-cell lung carcinoma. Surgical repair remains the treatment of choice but can be postponed or contraindicated. Bronchoscopic techniques may be an option with curative intent or as a bridge towards definitive surgery. The aim of the study is to evaluate the efficacy and the outcome of a new customised covered conical self-expandable metallic stent in the management of large bronchopleural fistulas complicating pneumonectomies. METHODS: A case series using chart review of non-operable patients presenting with large bronchopleural fistulas (>6mm) post-pneumonectomies as a definitive treatment with curative intent for non-small-cell lung carcinomas and requiring the use of a dedicated conical shaped stent in two tertiary referral centres. RESULTS: Seven patients presenting large post-pneumonectomy fistulas (between 6 and 12 mm) were included. Cessation of the air leak and clinical improvement was achieved in all the patients after stent placement. Stent-related complications (two migrations and one stent rupture) were successfully managed using bronchoscopic techniques in two patients and surgery in one. Mortality, mainly related to overwhelming sepsis, was 57%. Delayed definitive surgery was achieved successfully in three patients (43%). CONCLUSIONS: This case series assesses the short-term clinical efficacy of a new customised covered conical self-expandable metallic stent in the multidisciplinary management of large bronchopleural fistulas complicating pneumonectomies in patients deemed non-operable. Long-term benefits are jeopardised by infectious complications. PMID- 20591686 TI - Long-term results of surgical resection for pulmonary metastasis from renal cell carcinoma: a 25-year single-institution experience. AB - OBJECTIVE: Despite the report of new treatment options, surgery remains the best treatment for pulmonary metastases from renal cell carcinoma (RCC). Repeat resection is also an effective means for recurrent pulmonary metastases. The aim of the present study was to define the prognostic factors for survival after pulmonary metastasectomy from RCC based on a 25-year single-centre experience. METHODS: Between 1973 and 2008, 59 thoracotomies on 48 patients (38 men, 10 women) were performed in our hospital. Repeat resections were performed in eight patients. The clinicopathological and surgical data of these patients obtained from the medical records were analysed. The time interval between lung resection and death, or latest follow-up, ranged from 3 to 177 months (median 39 months). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Multivariate analysis was performed using the Cox multivariate proportional hazard model. RESULTS: The cumulative 3-, 5- and 10-year survival rates were 60%, 47% and 18%, respectively. Multivariate analysis identified disease-free interval (DFI) (>= 2 years) and complete resection as significant prognostic factors for survival. Among eight patients, who underwent repeat resection, two remain alive with no evidence of disease. These two patients had long DFI and long DFI-2 (time from first pulmonary metastasectomy to diagnosis of recurrent pulmonary metastasis). CONCLUSIONS: The results showed that (1) surgical resection of pulmonary metastasis from RCC has a favourable outcome in selected patients, (2) DFI and completeness of resection are prognostic markers for survival after pulmonary metastasectomy and (3) repeat lung resection for metastatic RCC is a safe procedure that provides satisfactory patient outcomes. PMID- 20591687 TI - Does the clover technique fit the annular physiology? PMID- 20591689 TI - Increased Th17 rather than Th1 alloimmune response is associated with cardiac allograft vasculopathy after hypothermic preservation in the rat. AB - BACKGROUND: Preservation injury decreases patient survival and promotes the development of cardiac allograft vasculopathy. We investigated the sequential effects of hypothermic preservation on ischemia-reperfusion injury (IRI), subsequent innate immune activation, and adaptive immune response in rat cardiac allografts. METHODS: Allografts were transplanted from fully major histocompatibility complex-mismatched Dark Agouti to Wistar Furth rats without pre-operative hypothermia or after 4 hours of hypothermic preservation. Recipients received cyclosporine A immunosuppression. The allografts were recovered at 6 hours (n = 6, 7), 24 hours (n = 6), 10 days (n = 5), and 8 weeks (n = 5). Immunohistochemical, histologic, and reverse-transcription polymerase chain reaction analysis was performed. RESULTS: In IRI, significantly increased messenger RNA (mRNA) levels for Toll-like receptor 4, hyaluronan synthases (HAS)1 2 (p = 0.03), high-mobility group box 1 (p = 0.05), CD80/83 (p = 0.01, p = 0.048), and the cytokines tumor necrosis factor-alpha (p = 0.004), interferon gamma (p = 0.012), and interleukin (IL)-6 (p = 0.019) were seen in allografts subjected to hypothermic preservation. During established alloimmune response, allografts subjected to hypothermic preservation expressed prominent infiltration of CD4+ T cells (p = 0.043) and dendritic cells (p = 0.029) and significantly up regulated mRNA levels of CD80 (p = 0.036), chemokine (C-C motif) ligand 21 (p = 0.008), C-C chemokine receptor type 7 (p = 0.003), vascular endothelial growth factor-C (p = 0.016), and vascular endothelial growth factor receptor-3 (p = 0.02). These allografts also showed prominent mRNA upregulation of Foxp3 (p = 0.014), IL-17 (p = 0.038), and IL-23 (p = 0.043). Preservation significantly increased the incidence and intensity of allograft arteriosclerosis (p < 0.05) and cardiac fibrosis (p = 0.003) at 8 weeks. CONCLUSION: Our results demonstrate that preservation injury induced a cascade leading to an innate immune response that modulated the adaptive immune response towards Th17 rather than Th1 T-cell response in rat cardiac allografts and ultimately enhanced cardiac fibrosis and arterial occlusion. Our results also suggest that this immune response was not regulated by the calcineurin inhibitor cyclosporine A. PMID- 20591690 TI - Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. AB - BACKGROUND: Skin cancer, in particular squamous cell carcinoma (SCC), is the most common malignancy after solid-organ transplantation. SCC has been reported in immunosuppressed patients receiving voriconazole, but the agent has not been shown to be a risk factor. Universal voriconazole prophylaxis and alemtuzumab induction are standard in our lung transplant program. METHODS: We performed a retrospective, case-control study (matched 1:3) among lung transplant recipients at our center from 2003 to 2008. RESULTS: SCC was diagnosed in 3.1% (17 of 543) of patients at a median follow-up of 36 months. Median time to development of SCC was 19 months post-transplant. Risk factors for SCC by univariate analysis included older age (p = 0.02), residence in locations with high levels of sun exposure (p = 0.0001), single-lung transplant (p = 0.02) and duration (p = 0.03) and cumulative dose (p = 0.03) of voriconazole. Duration of voriconazole (hazard ratio [HR] = 2.1; p = 0.04) and residence in locations with high sun exposure (HR = 3.8; p = 0.0004) were independent risk factors by multivariate analysis. SCC lesions were located on the head and neck in 94% of cases, and 53% had multiple lesions. All patients were treated with surgery. At least one independent lesion developed subsequently in 47% of patients. Local spread and distant metastases each occurred in 7% of cases. There were no deaths among the cases. CONCLUSIONS: Voriconazole exposure is a risk factor for SCC after lung transplantation, particularly among older patients living in areas with high sun exposure. Voriconazole should be used cautiously in these patients. PMID- 20591691 TI - Relationship between obesity and resting energy expenditure in systolic heart failure. PMID- 20591692 TI - Myeloperoxidase and carbonyl proteins: promising markers for non-invasive monitoring of graft rejection after heart transplantation. AB - BACKGROUND: After heart transplantation (HTx), endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. A non-invasive marker of rejection would be desirable as an alternative or to permit more selective use of the costly and invasive EMB. METHODS: In this retrospective study, outcomes of routinely taken EMBs were used to select 28 patients after HTx EMB Grade 0R (8 patients), 1R (9 patients) or 2R (11 patients). For these patients, myeloperoxidase (MPO) and carbonyl proteins (CP) in serum were measured using enzyme-linked immunoassay (ELISA). RESULTS: MPO and CP levels in post-HTx patients with Grade 2R rejection were significantly (MPO: p < 0.01; CP: p < 0.001) elevated at the time of rejection compared with levels 1 month earlier. MPO and CP levels predicted Grade 2R rejection and the best cut-off point was 237.5 MUg/l for MPO and 222.5 pmol/mg for CP, respectively. Clinically most important was the marked increase (doubling of basic values within 1 month) of MPO and CP levels in cases of Grade 2R rejection in post-HTx patients. CONCLUSIONS: MPO and CP seem to be appropriate parameters to monitor rejection events non-invasively and to minimize the application of EMBs after HTx. PMID- 20591694 TI - Late hematogenous infection of first metatarsophalangeal joint replacement: a case presentation. AB - Late hematogenous infection of previously asymptomatic orthopedic implants is extremely rare and usually associated with total joint replacements, such as those of the hip or knee. We present the case of an otherwise healthy female who developed a deep space infection 18 months after a first metatarsophalangeal joint implant arthroplasty. The patient presented with pain and swelling at the site, and over the course of several days developed fever and tachycardia and leukocytosis. Cultures of the surrounding soft tissues and the implant grew Streptococcus pneumoniae. The patient reported a 1- to 2-week history of symptoms consistent with an upper respiratory tract infection and it is believed that this distant focus of infection was the probable source of late hematogenous seeding of the first metatarsophalangeal joint implant. PMID- 20591695 TI - The value of digital tomosynthesis in the diagnosis of suspected pulmonary lesions on chest radiography: analysis of diagnostic accuracy and confidence. AB - RATIONALE AND OBJECTIVES: The aim of this study was to investigate the value of digital tomosynthesis in the diagnosis of suspected pulmonary lesions on chest radiography. MATERIALS AND METHODS: Two-hundred twenty-eight patients (133 men, 95 women; mean age, 70.8 +/- 11.1 years) with suspected pulmonary lesions after initial analysis of chest radiography underwent digital tomosynthesis. Two independent readers (with 3 and 20 years of experience) prospectively analyzed the chest radiographic and digital tomosynthesis images on a picture archiving and communication system workstation and proposed a diagnostic confidence score for each lesion (1 or 2 = definitely or probably extrapulmonary lesion or pseudolesion, 3 = indeterminate, 4 or 5 = probably or definitely pulmonary lesion). Chest computed tomography was the reference standard examination. RESULTS: A total of 251 suspected pulmonary lesions were identified. In 71 patients, digital tomosynthesis and computed tomography did not confirm any lesion. In the remaining 157 patients, 180 lesions were identified, including 112 pulmonary and 68 extrapulmonary lesions. In 110 (reader 1) and 123 (reader 2) lesions, correct diagnoses were provided after analysis of the chest radiographs. All lesions were correctly classified after digital tomosynthesis except for 14 extrapulmonary lesions (both readers) that were misinterpreted as pulmonary and 10 (reader 1) and six (reader 2) pulmonary lesions that were misinterpreted as pleural. Digital radiography versus tomosynthesis differed in accuracy (reader 1, 43% vs 90%; reader 2, 49% vs 92%; P < .05) and confidence by area under the receiver-operating characteristic curve (reader 1, 0.788 vs 0.944; reader 2, 0.840 vs 0.997; P < .05). CONCLUSIONS: Digital tomosynthesis improved diagnostic accuracy and confidence in the diagnosis of suspected pulmonary lesions on chest radiography. PMID- 20591696 TI - Prevalence and clinical characteristics of symptomatic patients with obstructive coronary artery disease in the absence of coronary calcifications. AB - RATIONALE AND OBJECTIVES: The quantification of coronary calcification has established itself as a valid risk marker to predict cardiovascular events. However, data derived from cardiac multi-detector row computed tomography could demonstrate that the exclusion of coronary calcification is not synonymous with the exclusion of coronary artery disease (CAD). The aims of this retrospective analysis were to determine the prevalence of significant CAD in a symptomatic cohort with indications for invasive angiography but without coronary calcification (Agatston score 0) as assessed by multislice computed tomography and to investigate whether there were any differences in terms of risk factors between patients with and without significant CAD. MATERIALS AND METHODS: Five hundred multislice computed tomographic scans (in 371 men and 129 women) were included in the analysis. Agatston scores were determined on native scans. All patients underwent coronary angiography to detect or rule out obstructive CAD. Patients with negative calcium scoring were selected and divided into two subgroups: those without obstructive CAD and those with obstructive CAD (luminal stenoses > 50%). These subgroups were characterized in terms of clinical characteristics (age and sex) and cardiovascular risk factors (diabetes mellitus, hypertension, hyperlipoproteinemia, familial predisposition, smoking, and overweight). RESULTS: Sixty-one of 500 patients (12.2%) had negative calcium scores (Agatston score 0). Sixteen of these patients (26.3%, or 3.2% of the total population) had obstructive CAD according to invasive angiography. Patients with obstructive CAD were significantly older (mean age, 64 +/- 9 vs 55 +/- 10 years; P = .003) and were more frequently diabetic (25% vs 4%, P = .0389) than patients without obstructive CAD. There were no significant differences with regard to the other risk factors. CONCLUSIONS: In this high-risk population, the absence of coronary calcification was not sufficient to rule out CAD. Among patients without coronary calcification, the presence of significant CAD was associated with increased age and the presence of diabetes mellitus. PMID- 20591698 TI - Evaluation of the caries profile and caries risk in adults with endodontically treated teeth. AB - OBJECTIVES: The present study was set up to explore (1) a potential association between a person's caries risk profile and the presence or absence of root-filled teeth, and (2) the caries risk in endodontically treated teeth. STUDY DESIGN: Two hundred Saudi adults were divided into an Endodontic Group (EG; n = 100), with a minimum of 2 root-filled teeth, and a Non-Endodontic Group (NEG; n = 100), without any root filling. Various caries risk factors were evaluated using a computer-based program (Cariogram). Clinical and radiographic examinations were also carried out. RESULTS: Cariogram findings showed that "the chance of avoiding caries" was low in both groups (35% in EG and 37% in NEG), and there was no statistically significant difference between the 2 groups. However, DMFS, recurrent caries, and mutans streptococcus count in saliva were significantly higher in the EG compared to the NEG (P < .05). When teeth in the EG were evaluated independently, the proportion of recurrent caries to the total fillings associated with endodontically treated teeth was 31.6% versus 19.2% in the non endodontically treated teeth. CONCLUSIONS: Data were not in favor of an association between caries risk profile and presence of root-filled teeth, but supported the notion that root-filling procedures might make the tooth more susceptible to caries. PMID- 20591697 TI - Reproducibility of forced expiratory tracheal collapse: assessment with MDCT in healthy volunteers. AB - RATIONALE AND OBJECTIVES: To assess the reproducibility of multidetector-row computed tomography (MDCT)-measured forced expiratory tracheal collapse in healthy volunteers. METHODS AND MATERIALS: Fourteen healthy, nonsmoking volunteers (6 males, 8 females, mean age 48.7 +/- 13.8 years) underwent repeat imaging 1 year after baseline imaging of tracheal dynamics employing the same scanner and technique (64-MDCT, 40 mAs, 120 kVp, and 0.625 mm detector collimation) with spirometric monitoring of total lung capacity and forced exhalation. Cross-sectional area (CSA) of the trachea was measured 1 cm above the aortic arch at end-inspiration and dynamic expiration, and percentage (%) expiratory reduction in tracheal lumen was calculated. Measurements were compared between baseline (Yr1) and repeat imaging (Yr2) using correlation coefficients and Bland-Altman plots. RESULTS: Mean end-inspiratory CSA was 255.3 +/- 56 mm(2) at Yr1 and 255.1 +/- 52 mm(2) at Yr2; mean dynamic expiratory CSA was 125.6 +/- 60 mm(2) at Yr1 and 132.1 +/- 58 mm(2) at Yr2; and mean % expiratory reduction was 51.7 +/- 18% at Yr1 and 48.7 +/- 19% at Yr2. Mean differences between Yr1 and Yr2 values were 0.2 mm(2) for end-inspiratory CSA, 6.5 mm(2) for dynamic expiratory CSA, and 3.0% for percentage expiratory reduction. There was excellent correlation between the Yr1 and Yr2 measures of end-inspiratory CSA (r(2) = 0.97, P < .001), dynamic expiratory CSA (r(2) = 0.89, P < .001), and % expiratory reduction (r(2) = 0.86, P < .001). CONCLUSION: MDCT measurements of forced expiratory tracheal collapse in healthy volunteers are highly reproducible over time. PMID- 20591699 TI - The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro-computed tomography. AB - OBJECTIVE: Many dental patients take bisphosphonates to reduce the risk of hip and vertebral fractures. In vivo micro-computed tomography (micro-CT) was used to examine the longitudinal inhibitory effect of alendronate on the healing of extraction sockets in ovariectomized rats. STUDY DESIGN: Twenty 5-week-old Sprague-Dawley rats were assigned randomly to 1 of 3 groups: sham-operated (n = 5), and 2 ovariectomized (OVX) groups: saline treated (0.1 mL/100 g/d, n = 7) and alendronate treated (1 mg/kg/d, n = 8). Before micro-CT scanning, the left maxillary first molars of the rats were extracted. In vivo micro-CT (spatial resolution 50 x 50 mum) of the jaw was performed at baseline and at 2-week intervals for 6 weeks. Alveolar-bone radiographic densities and dimensions were analyzed with repeated measures analysis of variance. The bony healing patterns of the extraction sockets were also evaluated in each group. RESULT: The radiographic socket densities of the sham-treated and OVX-alendronate groups significantly increased during the first 4 weeks after extraction (P < .05). At 2 weeks, the radiographic densities of the sockets in the OVX-saline group increased, but the increase was significantly lower than for the other groups at 4 weeks (P < .05). Newly formed bone was identified in the extraction sockets in all groups 2 to 6 weeks after extraction. There was a significant loss of alveolar ridge height at the second week postextraction compared with baseline, and at the fourth week compared with the second week (P < .05) except in the alendronate group. CONCLUSION: Alendronate appears to promote the healing of extraction sockets in estrogen-deficient rats and helps resist the loss of alveolar bone adjacent to extraction sockets. PMID- 20591700 TI - Integration accuracy of digital dental models and 3-dimensional computerized tomography images by sequential point- and surface-based markerless registration. AB - OBJECTIVE: The goal of this study was to evaluate the accuracy of the integration of computerized tomography (CT)-based bone models and laser-scanned dental models by sequential point- and surface-based markerless registration to create a digital maxillofacial-dental model. STUDY DESIGN: The integration accuracy was evaluated in normal skulls (group I) and subjects with maxillofacial deformities (group II) by measuring the distance between the integrated models (for group I and II) and between the final integrated model and the laser-scanned original skull model (for group I). RESULTS: The average error ranged between 0 and 0.2 mm without statistically significant difference in the region of maxilla or mandible and in tooth location. CONCLUSIONS: We could confirm that the integration can be made with good accuracy without the aid of fiducial markers for the maxillofacial dental composite model from the different resolution of CT and dental models. PMID- 20591701 TI - Maxillary reconstruction using microvascular free flaps. AB - OBJECTIVE: Loss of all or part of the maxilla as a result of tumor ablation has both functional and aesthetic consequences. Reconstruction of the maxilla remains a challenge despite the availability of several flaps and the skills of the prosthodontist. We have analyzed a series of maxillary resections that underwent flap reconstruction to guide planning of the rehabilitation of patients with such defects. STUDY DESIGN: The authors present 83 patients with various types of maxillary defects that were reconstructed with different microvascular free flaps. All clinical data, including data on the functional and aesthetic outcome, are analyzed. RESULTS: Flap transfer was successful in 80 of 83 patients who underwent maxillary reconstruction. Separation of the oral and nasal cavities was achieved in all cases. Flap compromise occurred in 6 cases, which made revision necessary. Three of these flaps were salvaged and 3 flaps failed. In 10 of 28 patients with transferred bone, osseointegrated implants were inserted and dentally rehabilitated with excellent functional and aesthetic results. CONCLUSION: Various types of maxillary defects can be reconstructed successfully using different microvascular free flaps. This procedure is challenging because of the anatomical site of reconstruction creating a steep learning curve. If the reconstruction is successful, both facial appearance and oral function can be improved. Microvascular flaps containing bone of the fibula, scapula, or iliac crest facilitate complete dental rehabilitation. PMID- 20591702 TI - Hematopoietic cells from Ube1L-deficient mice exhibit an impaired proliferation defect under the stress of bone marrow transplantation. AB - Following bone marrow transplantation, donor stem cells are recruited from their quiescent status to promote the rapid reconstitution in recipients. This dynamic process is tightly regulated by a complex of internal and external signals. Protein modification by the ubiquitin like modifier ISG15 (ISGylation) is strongly induced by type I interferons (IFNs). There are higher levels of type I IFNs and protein ISGylation in the bone marrow of recipients shortly after transplantation. In order to clarify the physiological function of protein ISGylation, we generated a mouse model that lacks protein ISGylation due to deficiency of ISG15 conjugating enzyme Ube1L (Ube1L(-/-)). In this report, we focused on the analysis of the hematopoietic system in Ube1L(-)(/)(-) mice in steady-state hematopoiesis and its potential protective role during bone marrow reconstitution. Here we demonstrated that In Ube1L(-/-) mice, steady-state hematopoiesis was unperturbed. However, transplantation experiment revealed a 50% reduction in repopulation potential of Ube1L-deficient cells at 3weeks posttransplantation, but no differences at 6 and 12weeks. A competitive transplantation experiment magnified and extended this phenotype. Cell cycle analysis revealed that under the condition with high levels of IFNs and protein ISGylation, the Ube1L deficiency can cause G2/M phase block of cell cycle in hematopoietic multipotential progenitors. These observations indicate that although protein ISGylation is dispensable for steady-state hematopoiesis, it plays a significant role during interferon related stress response, such as bone marrow transplantation. PMID- 20591703 TI - Adolescent and young adult women's use of emergency contraception. AB - STUDY OBJECTIVE: To determine differences in the use of emergency contraception (EC) between adolescent (11-17 years old) and young adult women (18-24 years old) in an insured, population based cohort. DESIGN AND PARTICIPANTS: Females 11-24 years old were divided into two groups: adolescents (11-17) and young adults (18 24) at their first captured EC prescription fill. A medical record review followed. MAIN OUTCOME MEASURES: The main outcomes of our study were reason for EC use, timing of EC use, and repeat use. Chi-square tests were used to compare dichotomous variables between groups by age and for ever vs repeat use. An independent t-test was used to compare continuous variables. A person-time analysis was used to compare rates of repeat use. RESULTS: 344 women were identified as having filled at least one prescription for an EC drug. Among ever users, adolescents were more likely than young adults to cite no contraception as their reason for seeking EC (30% for 11-17 and 24% for 18-24 year olds; P = 0.38). For both ever and repeat users, young adults reported condom failure as their main reason for seeking EC. We calculated t-tests on the hours since unprotected sex. For adolescents the mean was 42 hours and for young adults the mean was 34 hours (P = 0.13). Both are within the recommended 72-hour window for administration and were not significantly different. The rate of repeat use was essentially the same for both age groups. CONCLUSIONS: We found that adolescent use of EC was similar to young adult use and support the recommendation that 17 year-olds have behind-the-counter access to EC. PMID- 20591704 TI - Intramammary infections with the contagious Staphylococcus aureus genotype B in Swiss dairy cows are associated with low prevalence of coagulase-negative staphylococci and Streptococcus spp. AB - The association between the contagious Staphylococcus aureus genotype B (GTB) and the presence of coagulase-negative staphylococci (CNS) and Streptococcus spp. (non-agalactiae streptococci), was investigated, and the identification of problem herds without genotyping was evaluated. Milk samples from 10 herds with Staph. aureus GTB herd problems (PH cases) were compared with samples from 19 herds with at least one Staph. aureus isolate of non-B genotype (CH cases). All samples were bacteriologically analysed and Staph. aureus genotyping carried out using a ribosomal spacer-PCR. Cow and quarter prevalences of Staph. aureus, CNS and Streptococcus spp. differed significantly between PH and CH groups. PH cases were highly associated with decreased cow prevalences of CNS and Streptococcus spp. These altered prevalences also contributed significantly to the identification of problem herds without resorting to genotyping. Common herd level risk factors did not explain the difference between the prevalences in PH and CH cases. PMID- 20591705 TI - Increased efficacy of early spinal cord stimulation in an animal model of neuropathic pain. AB - Although spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain, pain relief is still not successful in a large group of patients. We suggest that the success of SCS may be related to the timing of SCS during the development of chronic neuropathic pain. We therefore compared the effect of SCS applied after 24h of neuropathic pain (early SCS) and after 16days of neuropathic pain (late SCS). For early SCS, male Sprague-Dawley rats (n=13) were implanted with an SCS device, followed by a partial ligation of the sciatic nerve. Using von Frey monofilaments, tactile allodynia was assessed 24h after ligation. Animals with tactile allodynia received 30min of SCS. Withdrawal thresholds were assessed just before SCS, during SCS and until the return to pre stimulation withdrawal threshold. Results were compared with the data from late SCS (n=29). Out of the 13 allodynic animals that received early SCS, 10 (77%) responded to SCS with significantly increased withdrawal thresholds, compared to 38% in the late SCS group. The increase of the withdrawal threshold in the early SCS group could still be noticed 90min after termination of SCS. In more than half of these animals, pre-stimulation withdrawal thresholds were reached only the next day. Early SCS resulted in an increased number of responders to SCS and furthermore an increased duration of the effect of SCS as compared to late SCS. Early SCS treatment of neuropathic rats is more effective as compared to the late SCS treatment. PMID- 20591706 TI - Improving the quality and reporting of systematic reviews. PMID- 20591707 TI - Pressure-induced muscle pain and tissue biomechanics: a computational and experimental study. AB - Pressure algometry is widely used to assess deep tissue sensitivity. In this study the relation between pressure-induced pain in humans and stress/strain distribution within the deep tissue is evaluated. A three-dimensional finite element computer model was used to describe the stress/strain distribution in tissues of the lower leg during pressure stimulation. The computer model was validated based on data recorded by computer-controlled pressure-induced muscle pain in eight subjects. An indentation of 7 mm was painful for all subjects and at this level data were extracted from each simulation. Simulations were performed with different stimulation sites (muscle, near-bone), probe diameters (5, 10, 15 mm), and probe designs (flat, rounded). The principal stress peaked in the skin and was reduced to about 10% in the underlying muscle tissue. The principal strain peaked in adipose tissue and was reduced in muscle tissue to 80% with the 15 mm probe and 66% with the 5mm probe. The large diameter probe evoked a strain peak in adipose tissue at 0.12 (flat probe) and 0.24 (rounded probe); in muscle tissue 0.10 and 0.20 respectively. The human pressure pain thresholds with the rounded probe were significantly lower compared with the flat probe (p<0.05). The results suggest that pressure-induced muscle pain is mainly related to muscle strain and most efficiently induced by large rounded probes, while smaller and flat ones mainly activate superficial structures. The relatively low stress in the deep tissue suggests that the mechanosensitivity of nociceptors in the deep tissue is lower compared with nociceptors in the superficial tissue. PMID- 20591708 TI - Deletion at chromosomal band Xp22.12-Xp22.13 involving PDHA1 in a patient with congenital lactic acidosis. AB - We present a patient with congenital lactic acidosis, agenesis of the corpus callosum, and profound developmental delay. Assays of pyruvate dehydrogenase complex function were normal in lymphocytes, but decreased in fibroblasts. Sequencing of the PDHA1 gene did not reveal deleterious mutations, and BAC based microarray analysis did not reveal any chromosomal abnormality. However, gene dosage analysis with oligonucleotide-based chromosomal microarray revealed a deletion of Xp22.12-Xp22.13 involving complete deletion of PDHA1. This is the first report of a whole gene deletion of PDHA1 detected by oligonucleotide-based microarray. PMID- 20591709 TI - Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2. AB - Griscelli syndrome (GS), a rare autosomal recessive disorder characterized by partial albinism and immunological impairment and/or severe neurological impairment, results from mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes. We identified a Hispanic patient born of a consanguineous union who presented with immunodeficiency, partial albinism, hepatic dysfunction, hemophagocytosis, neurological impairment, nystagmus, and silvery hair indicative of Griscelli Syndrome Type 2 (GS2). We screened for point mutations, but only exons 2-6 of the patient's DNA could be PCR-amplified. Whole genome analysis using the Illumina 1M-Duo DNA Analysis BeadChip identified a homozygous deletion in the patient's DNA. The exact breakpoints of the 47.5-kb deletion were identified as chr15q15-q21.1: g.53332432_53379990del (NCBI Build 37.1); the patient lacks the promoter and 5'UTR regions of RAB27A, thus confirming the diagnosis of GS2. PMID- 20591710 TI - Rapid determination of C4-acylcarnitine and C5-acylcarnitine isomers in plasma and dried blood spots by UPLC-MS/MS as a second tier test following flow injection MS/MS acylcarnitine profile analysis. AB - BACKGROUND: Flow-injection MS/MS methods for elevated acylcarnitines are routinely performed in most newborn screening and biochemical genetics laboratories; however this technique cannot distinguish between isobaric compounds; therefore, chromatographic separation is required to quantitate isomers for differential diagnosis of some inborn errors of metabolism. METHODS: A UPLC-MS/MS method has been developed for the simultaneous quantitation of isobutyrylcarnitine and butyrylcarnitine, and a second UPLC-MS/MS method for the quantitation of isovalerylcarnitine, (S) and (R) 2-methylbutyrylcarnitine, pivaloylcarnitine and valerylcarnitine. Plasma and dried blood spots samples are extracted with methanol and derivatized with butanolic HCl. Deuterium labeled internal standards are used for quantitation. Separation is obtained using a methanol/water gradient with a C18 BEH, 1x100mm, 1.7microm UPLC column, at 60 degrees C; run time is less than 10min. The isomers are detected with a Quattro Premier triple quadrupole, with electrospray ionization in positive ion mode. RESULTS: Intra-day precision in plasma and dried blood spots ranged from 1.4% to 14% and accuracy from 88% to 114% respectively for butyrylcarnitine and isobutyrylcarnitine. Precision for the isomers of C5-acylcarnitine ranged from 1.3% to 15% and accuracy 87% to 119%, respectively in plasma or dried blood spots. Inter-day precision was within 20% at each concentration of isobutyrylcarnitine and butyrylcarnitine. Precision for 2-methylbutyrylcarnitine and isovalerylcarnitine at concentrations above the normal range was within 24%. CONCLUSIONS: Two diagnostic tests based on the separation of C4-acylcarnitine and C5-acylcarnitine isomers by UPLC-MS/MS provide fast differential diagnosis of SCAD deficiency versus IBCD deficiency and IVA versus 2-MBCD deficiency. The separation of C5-acylcarnitines can reveal false elevation due to pivalic acid containing antibiotics. Abnormal newborn screen results due to pivalate generating prodrug antibiotics of maternal origin were confirmed. This separation of isomers can resolve multiple diagnostic challenges in both newborn screening and in cases with ambiguous metabolic test results. PMID- 20591711 TI - A comparative contrast perception phantom image of brain CT study between high grade and low-grade liquid crystal displays (LCDs) in electronic medical charts. AB - The purpose of this study was to clarify whether non-medical-grade liquid crystal displays (LCDs) are acceptable for the soft-copy reading of brain CTs. Four kinds of color LCDs with different image quality levels were used: medical-grade LCD, low-grade general LCD calibrated with the grayscale display function (GSDF), low grade general LCD calibrated with gamma 2.2 and a notebook personal computer display panel. In Osirix's standard window setting for brain CTs, the average CT values of brain parenchyma in 100 cases were correlated with a grayscale level ranging from 71 to 91 in a 256-step grayscale. At these gray levels, the image contrast on the two low-grade LCDs calibrated with gamma 2.2 was higher than that on the medical-grade LCD. Eleven healthy volunteers participated in the contrast perception study, which used electronically generated target phantom images that simulated subtle abnormalities with a low or high attenuation difference in brain parenchyma. The three low-grade LCDs showed correct response rates and reaction times that were superior to those of the medical-grade display. The grayscale calibrations, GSDF or gamma 2.2, are likely to be more critical than the display grade, suggesting that the use of a low-grade LCD may be acceptable in the image contrast of brain CT. PMID- 20591712 TI - [Assessment and learning from the 27th Conference of the Spanish Society for quality in healthcare]. AB - OBJECTIVE: To analyse the results of the 27th Conference of the Spanish Society for Quality in Health Care (SECA) held in Seville (October 2009). MATERIAL AND METHODS: A retrospective descriptive study was conducted using the conference databases. POPULATION: All abstracts received (1231). 36 pairs of reviewers using explicit criteria evaluated abstracts and assignment as Experiences or Electronic Communications. Participant satisfaction in the Conference and Workshops was evaluated by an anonymous questionnaire. RESULTS: A total of 1213 communications were accepted. The average score of accepted abstracts was 6.38 +/- 0.95 points. Experiences had an average score of 7.55 +/- 0.41 points, while Electronic Abstracts had an average score of 6.26 +/- 0.9 points. Andalusia (557) and Catalonia (140) had the highest amount of abstracts in the Conference, but Murcia and Andalusia obtained the highest rates per million inhabitants. CONCLUSIONS: The assessment of abstracts and organising a national conference are methodologically complex processes. Accountability for actions and decisions made by the Organising and Scientific Committees are an ethical requirement of transparency. PMID- 20591713 TI - [Quality of professional life (QoPL) among primary care workers in area 7 of the Madrid Autonomous Region]. AB - OBJECTIVE: To describe the QoPL as perceived by Primary Care workers in the Primary Care Area 7 and to describe the progress since 2004. MATERIAL AND METHODS: Cross - sectional study carried out in the Primary Care Area 7 in June 2008. Participants were all primary care workers (n=1003). Main measurements were: the CVP-35 questionnaire (anonymous and self-administered) and socio demographic and professional variables that could be associated with QoPL. Results were compared to those obtained in previous years (2004-2006). RESULTS: Positive answers: 47%. By dimension, average scores were: perception of demands: 6.09, managerial support: 5.10 and intrinsic motivation: 7.56. Nurses, physiotherapists, and nursing assistants had significantly higher scores in intrinsic motivation, managerial support and quality of life. The individuals who carried out management activities had higher scores in managerial support and intrinsic motivation items. Slight improvements were seen in perception of demands, managerial support and quality of life. CONCLUSIONS: Item analysis allows us to develop improvement plans and subsequently evaluate their results. In this sense, we observed slight improvements, according to planned strategies, based on perceived demands in previous years. Some of these strategies have been recently introduced, so future evaluations using the CVP-35 questionnaire are needed in order to analyse their effectiveness. PMID- 20591714 TI - Two decades of battle against polio: opening a window to examine public health in China. AB - During a two-decade battle against polio, the Chinese government has saved more than one million children from physical disability caused by wild poliovirus infection. Today, the Chinese government still faces an arduous task in (1) preventing the entry and transmission of wild poliovirus from surrounding polio endemic countries, (2) finding and stopping the outbreak of polio caused by the recycling of vaccine-derived poliovirus, (3) reducing vaccine-associated paralytic poliomyelitis (VAPP) cases, and (4) improving the State compensation system. The scientific monitoring system established in China and the immunity strategy implemented not only allow children in China to avoid lifelong disability or premature death due to polio infection, but also provide success stories for the World Health Organization that can be used for the specification of quality control indices for monitoring polio, classification and diagnosis criteria for acute flaccid paralysis cases, and identification and emergency treatment principles for imported wild poliovirus. PMID- 20591715 TI - Primary localized histoplasmosis with lesions restricted to the mouth in a Chinese HIV-negative patient. AB - Histoplasmosis is a deep mycosis caused by Histoplasma capsulatum, which is endemic in many areas of the world but is relatively rare in China. Although the majority of cases present as a mild to moderate flu-like disease requiring only supportive therapy, approximately 1% of patients experience more serious pulmonary and extrapulmonary disease, which can be life-threatening if diagnosis is delayed or the treatment is not initiated rapidly. Definitive diagnosis is usually made by a combination of culture, detection of the organism in tissues, measurement of antibodies, and detection of antigen. We present the case of a 51 year-old patient who presented with histoplasmosis only, with several ulcerated lesions in the oral cavity and without HIV infection, who did not show any detectable signs and symptoms of systemic disease or extra-oral manifestations. Histopathological analysis indicated a chronic inflammatory process with granulomas with yeast-like organisms. Isolation of H. capsulatum and molecular identification provided the definitive diagnosis. Treatment with oral itraconazole led to remission of the oral lesions. This is the first Chinese case report of localized histoplasmosis with lesions restricted to the mouth in an HIV negative patient. PMID- 20591716 TI - Radiographic improvement and its predictors in patients with pulmonary tuberculosis. PMID- 20591717 TI - [Normal tissue tolerance to external beam radiation therapy: lung]. AB - Radiation pneumonitis is the most common dose limiting complication of thoracic radiation. Clinically significant radiation pneumonitis usually develops in 10 20% of patients. Characteristic clinical features associated with radiation pneumonitis include dyspnea, non-productive cough, radiographic opacification confined to the outlines of the field of radiation treatment and changes in pulmonary function measures. The risk of radiation pneumonitis is related to the cumulative dose of radiation to normal tissue and to patients and tumor features. Some studies demonstrated that preexisting pulmonary lung dysfunction, tumour location in lower lobes, use of concurrent chemotherapy could increase the risk of radiation pneumonitis. Controversies persist about which dosimetric parameter optimally predicts the risk of radiation pneumonitis. Mean lung dose, V20 and V30 are the most studied parameters. However, no ideal dosimetric parameter has been identified. The objective of this review is to summarize predictive factors of radiation pneumonitis, and to evaluate the predictive ability of various dose volume histogram parameters for routine practice. PMID- 20591718 TI - [Good knowledge and respect for dosage tolerance of organs at risk and healthy tissues is one of the major aspects of the profession of radiotherapeutic oncology]. PMID- 20591719 TI - [Evaluation of the dose received by organs at risk]. AB - The arrival of new technologies and the increase of the possible planned treatments require tools to evaluate and compare the delivered dose to specific organs at risk. Among several options providing the same tumour control, the choice will be made in favour of those that best spare the organs at risk. The evaluation tools have to report acute and late complications, and to be simple to use. The evaluation of the delivered dose to specific organs at risk is currently based on dose-volume histograms, conformal index and the integral dose. However, many questions remain as to reducing the normal tissue toxicity: is it better to deliver a relatively lower dose over a large volume or a relatively higher dose over a smaller volume? The long-term clinical follow-up of patients remains necessary. PMID- 20591721 TI - Axial osteomalacia: a new case report. PMID- 20591722 TI - Shifting attention to neurons. PMID- 20591723 TI - A computational foundation for cognitive development: comment on Griffths et al. and McLelland et al. PMID- 20591724 TI - Parasites in motion: flagellum-driven cell motility in African trypanosomes. AB - Motility of the sleeping sickness parasite, Trypanosoma brucei, impacts disease transmission and pathogenesis. Trypanosome motility is driven by a flagellum that harbors a canonical 9+2 axoneme, together with trypanosome-specific elaborations. Trypanosome flagellum biology and motility have been the object of intense research over the last two years. These studies have led to the discovery of a novel form of motility, termed social motility, and provided revision of long standing models for cell propulsion. Recent work has also uncovered novel structural features and motor proteins associated with the flagellar apparatus and has identified candidate signaling molecules that are predicted to regulate flagellar motility. Together with earlier inventories of flagellar proteins from proteomic and genomic studies, the stage is now set to move forward with functional studies to elucidate molecular mechanisms and investigate parasite motility in the context of host-parasite interactions. PMID- 20591725 TI - Highly selective and sensitive colorimetric probes for hypochlorite anion based on azo derivatives. AB - Two oxime-based colorimetric probes for the hypochlorite anion (ClO(-)) have been rationally designed and synthesized on basis of the mechanism of intramolecular charge transfer (ICT). Upon addition of ClO(-), the probes displayed around 20nm redshift in the absorption maximum, accompanied with the color change from orange to pink, which were attributed to the reaction of the oxime groups with ClO(-) to form aldehyde groups. The probes were highly selective for ClO(-) detection without the interference of other ions and oxidants. PMID- 20591726 TI - Spectroscopy of selected copper group minerals: Chalcophyllite and chenevixite implications for hydrogen bonding. AB - NIR and IR spectroscopy has been applied for detection of chemical species and the nature of hydrogen bonding in arsenate complexes. The structure and spectral properties of copper(II) arsenate minerals: chalcophyllite and chenevixite are compared with copper(II) sulphate minerals: devilline, chalcoalumite and caledonite. Split NIR bands in the electronic spectrum of two ranges 11,700-8500 cm(-1) and 8500-7200 m(-1) confirm distortion of octahedral symmetry for Cu(II) in the arsenate complexes. The observed bands with maxima at 9860 and 7750 cm(-1) are assigned to Cu(II) transitions (2)B(1g)-->(2)B(2g) and (2)B(1g)-->(2)A(1g). Overlapping bands in the NIR region 4500-4000 cm(-1) is the effect of multi anions OH(-), (AsO(4))(3-) and (SO(4))(2-). The observation of broad and diffuse bands in the range 3700-2900 cm(-1) confirms strong hydrogen bonding in chalcophyllite relative to chenevixite. The position of the water bending vibrations indicates the water is strongly hydrogen bonded in the mineral structure. The strong absorption feature centred at 1644 cm(-1) in chalcophyllite indicates water is strongly hydrogen bonded in the mineral structure. The H(2)O bending vibrations shift to low wavenumbers in chenevixite and an additional band observed at 1390 cm(-1) is related to carbonate impurity. The characterisation of IR spectra by nu(3) antisymmetric stretching vibrations of (SO(4))(2-) and (AsO(4))(3) ions near 1100 and 800 cm(-1) respectively is the result of isomorphic substitution for arsenate by sulphate in both the minerals of chalcophyllite and chenevixite. PMID- 20591727 TI - Regional differences in ulnar nerve excitability may predispose to the development of entrapment neuropathy. AB - OBJECTIVE: To assess whether there are differences in nerve excitability properties between proximal and distal stimulation sites in the ulnar nerve in healthy controls, which may provide information on whether alteration in ion channel function predisposes to the development of ulnar neuropathy at the elbow. METHODS: Nerve excitability studies were undertaken in 11 healthy controls. Studies were undertaken with stimulation of the ulnar nerve at the elbow and wrist. Recordings were obtained from abductor digiti minimi in both sets of studies. RESULTS: Recordings obtained following stimulation of the nerve at the elbow demonstrated significant differences to those obtained following stimulation of the nerve at the wrist. Specifically, there was a left shift in stimulus-response curves at the elbow compared to the wrist, with prolonged strength-duration time constant, and reduced rheobase (P<0.05). These changes were accompanied by increased refractoriness and reductions in superexcitability and late subexcitability (P<0.05). CONCLUSIONS: The present findings may suggest relative depolarization of ulnar nerve axons at the elbow. SIGNIFICANCE: These changes may reflect regional differences in axonal Na(+)/K(+) pump function and thereby predispose the ulnar nerve to conduction failure and axonal degeneration when exposed to trauma. PMID- 20591728 TI - Abnormal visual habituation in pediatric photosensitive epilepsy. AB - OBJECTIVE: To investigate visual habituation - a measure of visual cortical excitability - in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. METHODS: We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75-P100 and P100-N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75-P100 and P100-N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75-P100 and P100-N145 latencies was also analyzed. RESULTS: Statistical analysis revealed significant differences between the three groups in the slope index of N75-P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. CONCLUSIONS: Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. SIGNIFICANCE: This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age. PMID- 20591729 TI - Effect of gender on ocular vestibular-evoked myogenic potentials via various stimulation modes. AB - OBJECTIVE: This study compared the characteristic parameters of ocular vestibular evoked myogenic potentials (oVEMPs) via air-conducted sound (ACS), bone-conducted vibration (BCV), and galvanic vestibular stimulation (GVS) modes between male and female adults to determine whether gender affects oVEMPs. METHODS: Twenty healthy volunteers, 10 males (age, 24-33 years) and 10 females (age, 24-33 years), underwent oVEMP tests using ACS, BCV and GVS modes. RESULTS: No significant differences existed in the mean nI latency, pI latency and nI-pI interval between the males and females. However, the mean oVEMP amplitude in males was significantly larger than that of females, regardless of whether ACS, BCV or GVS mode was used. In contrast, asymmetry ratio of the amplitude did not show gender difference. Additionally, the mean body mass index (BMI) was 22.3 +/- 1.8 kg/m(2) for male group and 19.6 +/- 1.6 kg/m(2) for female group. Significant correlations existed between the BMI and oVEMP amplitude. CONCLUSIONS: Gender difference exists in oVEMP amplitude, which may be attributed to variance in the muscle bulk between males and females. SIGNIFICANCE: Ocular VEMPs should be interpreted with the asymmetry ratio rather than raw amplitude itself. PMID- 20591730 TI - Impaired neuronal synchrony after focal ischemic stroke in elderly patients. AB - OBJECTIVE: This study investigated whether cortical synchrony derived from electroencephalography (EEG) in elderly patients is impaired and if the impairment might reflect long-term functional recovery after stroke. METHODS: The scalp EEG signals of stroke patients (N=42) were collected within seven days after the onset of stroke and analyzed with phase synchronization (PS). Neurodeficit outcome was scored twice according to the National Institute of Health Stroke Scale (NIHSS): (1) at the same day of EEG recording and (2) two months after stroke. The correlation between cortical synchrony and NIHSS was analyzed. RESULTS: The level of synchronization between lesion and intact areas in the ipsilateral hemisphere was reduced significantly after stroke, while the synchronization among intact areas increased to 114% among the control subjects. Furthermore, the patients with lower inter-hemispheric synchrony after stroke were observed to have a higher NIHSS two months after stroke. CONCLUSIONS: Results indicated that the infarct broke down the cortical synchrony networks and affected large-scale neural communication. Inter-hemispheric synchrony was relevant to long-term functional recovery after stroke. SIGNIFICANCE: The prognostic value of PS for functional recovery after stroke might be helpful in understanding the alteration of cortical networks after ischemic injury. PMID- 20591731 TI - Preparation of arrays of cell spheroids and spheroid-monolayer cocultures within a microfluidic device. AB - This study describes a novel method for generation of an array of three dimensional (3D) multicellular spheroids within a microchannel in patterned cultures containing one or multiple cell types. This method uses a unique property of a cross-linked albumin coated surface in which the surface can be switched from non-adhesive to cell adhesive upon electrostatic adsorption of a polycation. Introduction of a solution containing albumin and a cross-linking agent into a microchannel with an array of microwells caused the entire surface, with the exception of the interior of the microwells, to become coated with the cross-linked albumin layer. Cells that were seeded within the microchannel did not adhere to the surface of the microchannel and became entrapped in the microwells. HepG2 cells seeded in the microwells formed 3D spheroids with controlled sizes and shapes depending upon the dimensions of the microwells. When the albumin coated surface was subsequently exposed to an aqueous solution containing poly(ethyleneimine) (PEI), adhesion of secondary cells, fibroblasts, occurred in the regions surrounding the arrayed spheroids. This coculture system can be coupled with spatially controlled fluids such as gradients and focused flow generators for various biological and tissue engineering applications. PMID- 20591732 TI - Efficient production of an antibody Fab fragment using the baculovirus-insect cell system. AB - The production of an Fab fragment of the catalytic antibody 6D9 in lepidopteran insect cells infected with a recombinant baculovirus that contained both the heavy chain (Hc) and light chain (Lc) genes of the Fab fragment was investigated. Western blotting and enzyme-linked immunosorbent assay (ELISA) of culture supernatant showed that baculovirus-infected Trichoplusia ni BTI-TN-5B1-4 (High Five) cells secreted an Fab fragment that retained antigen-binding activity. Infection of High Five cells with a recombinant baculovirus, in which the Lc and Hc genes were located downstream of the baculovirus p10 and polyhedrin promoters, respectively, produced a higher Fab fragment yield than that obtained with a baculovirus in which the Hc and Lc genes were downstream of the p10 and polyhedrin promoters, respectively. Baculovirus-infected High Five cells secreted more of the Fab fragment than Spodoptera frugiperda Sf9 cells. Moreover, use of the baculovirus gp64 signal sequence upstream of the Lc and Hc genes resulted in greater yield of the secreted Fab fragment than use of the insect-derived BiP and melittin signal sequences. Consequently, the Fab fragment was obtained in a high yield (>600 MUg/ml) in a shake-flask culture of High Five cells infected at a multiplicity of infection (MOI) of 10 plaque-forming units (pfu)/cell with the recombinant baculovirus in which the Lc and Hc genes with the gp64 signal sequence were expressed under the control of the p10 and polyhedrin promoters, respectively. These results indicate that the baculovirus-insect cell system may allow efficient production of antibody Fab fragments. PMID- 20591733 TI - "I see my mother's face": student nurse experiences caring for cancer patients. AB - PURPOSE: With the numbers of cancer diagnoses increasing annually and the aging of the global citizenry, it is certain that more nurses with expert competencies in cancer care will be needed. Nursing students must have a broad understanding of cancer content in order to provide safe, effective care in the clinical setting as they learn to recognize their own experiences in caring for cancer patients. Experienced nursing educators are aware that student nurses bring into any clinical learning situation their unique knowledge, values, fear, uncertainty and bias. The purpose of this study was to examine the experiences of nursing students caring for cancer patients. METHOD: This descriptive qualitative study included participants who were Junior or Senior Baccalaureate nursing students and had provided care for at least one patient with cancer during clinical experiences. Focus group interviews were transcribed verbatim for analysis and coding using accepted qualitative techniques. RESULTS: Data analysis revealed student experiences to be varied in the type of cancer patient experiences. Four prevalent sub-themes emerged regarding student experiences: caring for patients and families, interactions between students and healthcare providers, student experiences with dying patients, and students' prior experiences with cancer. Further discussion with students revealed a student perspective for strengthening cancer in the curriculum. CONCLUSION: Preparing students to be comfortable with cancer patients across the cancer illness trajectory will provide students with the necessary skills to gain confidence in their cancer patient care. PMID- 20591734 TI - Black women and breast health: a review of the literature. AB - AIM: In the UK, it is known that screening inequalities exist involving ethnic minority groups such as Black women (Patnick, 2009). To date, there is limited UK data on Black British women and breast health awareness. Black British women appear to be an underrepresented group in breast cancer studies (Breast Cancer Care, 2004, 2005). This literature review aimed to explore Black women's perceptions of breast health and factors that influence breast cancer screening practices. METHODS: A literature search for the period 1994 to September 2009 was undertaken using BNI, CINAHL, PubMed, OSH-ROM, PsyInfo, Google scholar, and Scopus databases. Key words used included: breast cancer, breast health, African American women, Black British women, black women, breast cancer screening, qualitative studies. Hand-searching was also done, and reference lists of papers were examined for relevant studies. RESULTS: Black women hold a variety of views and perceptions on the risk that breast cancer poses. These perceptions are strongly related to existing knowledge, related stigmatization, spiritual and religious beliefs, all of which can adversely influence motivation to engage in self-breast examination and breast cancer screening. CONCLUSION: US based studies identified several influential factors: religion, educational awareness of breast cancer screening, breast health awareness. Breast health interventions and research are needed to increase breast health awareness in Black British women. PMID- 20591735 TI - Early avoidance of disease- and treatment-related distress predicts post traumatic stress in parents of children with cancer. AB - PURPOSE OF THE RESEARCH: It has previously been demonstrated that parents of children with cancer often exhibit symptoms of post-traumatic stress (PTSS) even though the child's treatment is successfully completed. For the development of interventions we need to identify predictors of PTSS, which are possible to influence. Based on contemporary learning theory, it was hypothesized that early avoidance of disease- and treatment-related distress would predict the development of parental post-traumatic stress after completion of the child's cancer treatment. METHODS AND SAMPLE: Parents' cognitive and behavioural avoidance of disease- and treatment-related distressing stimuli during and immediately after a child's cancer treatment and PTSS one year after the end of treatment was investigated. Data was collected with the PTSD Checklist Civilian Version (PCL-C) from 111 mothers and 109 fathers. KEY RESULTS: As hypothesized, avoidance during (T1-T3) and immediately after (T4) the child's treatment predicted PTSS among parents one year after (T6) completion of the child's treatment. Moreover, avoidance early on during the child's treatment seemed to be a greater risk factor for PTSS and post-traumatic stress disorder (PTSD) for bereaved than non-bereaved parents. CONCLUSIONS: Avoiding reminders of stressful experiences related to a child's cancer disease during and immediately after the child's treatment seems to increase the risk for parents, mothers and fathers alike, of experiencing symptoms of post-traumatic stress later. Interventions based on cognitive behavioural therapy with elimination of avoidance as a central component may be of use in this population. PMID- 20591736 TI - Airway remodeling in asthma. AB - Asthmatic airway remodeling is the pathophysiological modifications of the normal airway wall structure which include changes in the composition and organization of its cellular and molecular constituents. These modifications are the major cause of the symptoms associated with decreased pulmonary function. Airway remodeling is partially reversible in mild asthma but mostly irreversible in chronic severe asthma. It is initiated as a repair process in response to airway wall injuries caused by inflammation; however, dysregulation of this process leads to airway remodeling. In this review, we will summarize the most recent findings about the different structural changes in airways of asthmatics as well as mediators involved in this process. PMID- 20591737 TI - New lessons about old molecules: how type I interferons shape Th1/Th17-mediated autoimmunity in the CNS. AB - Type I interferons (IFN-alpha and IFN-beta) were discovered more than five decades ago and are widely used for the treatment of human autoimmune diseases such as multiple sclerosis (MS). Despite their highly beneficial features, the precise mechanism of action remains speculative. Given the frequent side effects of IFN-alpha/beta therapy, understanding its action in an in vivo setting is vital to further improve this therapeutic approach. Major advances in our understanding of the IFN biology have recently been made and are particularly based on the combination of powerful genome-wide expression analysis in humans with gene-targeting techniques available for basic research. The recent discovery of a novel T-cell subset, Th17 cells, sheds new light on type I IFNs in MS. PMID- 20591738 TI - Programmed cell death in unicellular parasites: a prerequisite for sustained infection? AB - The detection of markers typical for metazoan programmed cell death (PCD) in diverse protozoan parasites raised a debate about the evolution of PCD processes and its impact on the biology of single-celled parasites. By applying the unified criteria recently developed for metazoan cell death, the conclusion is made that cell death in protozoan parasites also occurs in a programmed fashion. Several molecules or pathways which regulate PCD in higher eukaryotes have been implicated in the death of unicellular parasites. Furthermore, we emphasize that PCD enables the regulation of parasite densities in distinct host compartments and aids in avoiding inflammatory responses, thereby facilitating a sustained infection. We therefore propose that PCD pathways might represent ideal targets to combat protozoan parasites by their own means. PMID- 20591739 TI - Bringing neglected tropical diseases into the spotlight. AB - The correlation between poverty and the neglected tropical disease (NTD) burden is undeniable. NTDs are a brand without copyright; an international movement gathering momentum towards a common goal of tackling major causes of preventable illness in low-income countries. New reports by Liese and Schubert and Moran et. al. act as a call to arms, highlighting a need for research into NTD treatment and control that is essential to improving the lives of the 'bottom billion.' PMID- 20591740 TI - Determinants of fruit and vegetable availability in Hispanic head start families with preschool-aged children living in an urban midwestern area. AB - OBJECTIVE: Determine relationships between self-efficacy, decisional balance, and processes of change and Stages of Change (SOC) related to fruit and vegetable (FV) availability among Hispanic Head Start parents. DESIGN: A 2-phase descriptive study with mixed methodology. SETTING: Two Head Start sites in a city in the midwestern United States. PARTICIPANTS: Convenience sample of Hispanic Head Start parents/guardians recruited to complete a FV survey and focus groups. MAIN OUTCOME MEASURES: Amount of FV served; distribution of participants between SOC; level of self-efficacy, decisional balance, and use of cognitive and behavioral processes. ANALYSIS: Analysis of variance was conducted using the SOC as the independent variable and Transtheoretical Model construct scales as dependent variables. Significance was set at P < .05. Focus groups were analyzed using content analysis. RESULTS: Of the 113 participants, 60% were in pre-action stages. Compared to those of parents in higher stages, intentions of parents in lower stages to serve more FV were impeded by cost and preparation time (P = .028). Focus groups confirmed low self-efficacy as the common barrier to serving more FV. CONCLUSIONS AND IMPLICATIONS: Nutrition education for low-income Hispanic parents should include components focused on increasing self-efficacy and minimizing perceived barriers; quick and tasty FV recipes; shopping for economical FV; and promoting parental role modeling. PMID- 20591741 TI - Factors associated with abnormal eating attitudes among Greek adolescents. AB - OBJECTIVE: To estimate the prevalence of abnormal eating attitudes among Greek adolescents and identify possible risk factors associated with these attitudes. DESIGN: Cross-sectional, school-based study. SETTING: Six randomly selected schools in Patras, southern Greece. PARTICIPANTS: The study population consisted of 540 Greek students aged 13-18 years, and the response rate was 97%. MAIN OUTCOME MEASURE: The dependent variable was scores on the Eating Attitudes Test 26, with scores > or = 20 indicating abnormal eating attitudes. ANALYSIS: Bivariate analysis included independent Student t test, chi-square test, and Fisher's exact test. Multivariate logistic regression analysis was applied for the identification of the predictive factors, which were associated independently with abnormal eating attitudes. A 2-sided P value of less than .05 was considered statistically significant. RESULTS: The prevalence of abnormal eating attitudes was 16.7%. Multivariate logistic regression analysis demonstrated that females, urban residents, and those with a body mass index outside normal range, a perception of being overweight, body dissatisfaction, and a family member on a diet were independently related to abnormal eating attitudes. CONCLUSIONS AND IMPLICATIONS: The results indicate that a proportion of Greek adolescents report abnormal eating attitudes and suggest that multiple factors contribute to the development of these attitudes. These findings are useful for further research into this topic and would be valuable in designing preventive interventions. PMID- 20591742 TI - Regulation of IL-8 production by complement-activated product, C5a, in vitro and in vivo during sepsis. AB - Excessive complement-activated product complement 5a (C5a) has been implicated in the pathogenesis of sepsis development. Herein, we employed in vitro and in vivo models of sepsis to investigate the functional relationship between overtly produced C5a and IL-8. Our data revealed that C5a could strongly amplify IL-8 expression from human whole blood cells induced by LPS and other types of TLR agonists. ERK1/2 and p38, but not JNK, were mainly participated in signaling pathways for IL-8 production. In the whole blood stimulated by Escherichiacoli, C5a levels were quickly elevated and blockage of C5a significantly decreased E. coli-elicited IL-8 production. In the mouse model of sepsis induced by cecal ligation and puncture (CLP), the markedly increased keratinocyte-derived cytokine (KC) could be strongly suppressed by blockage of C5a. These data suggest that excessive C5a functions as a critical inflammatory mediator to enhance IL-8 production mainly through MAPK signaling pathways. PMID- 20591743 TI - Abortion and post-abortion care - volume II. Preface. PMID- 20591744 TI - Differential effects of seizure control and affective symptoms on quality of life in people with epilepsy. AB - OBJECTIVE: The purpose of the study was to delineate how affective symptoms (AS) influence quality of life (QOL) for individuals with drug-refractory epilepsy (DRE) and those with well-controlled epilepsy (WCE) independently. METHODS: All subjects participating in the study were asked to complete reliable and validated self-report health questionnaires, including AS, measured with the Korean versions of the Beck Depression Inventory, Beck Anxiety Inventory, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We examined predictors of QOLIE-31 scores among the various demographic and clinical factors. We compared the effects of AS on QOL between patients with DRE and those with WCE and investigated the differential effects of seizure control and AS on QOL. RESULTS: Two hundred forty-nine patients with DRE or WCE were included in the study. The strongest predictor of QOL was AS, followed by seizure control and MRI abnormality. Affective symptoms had almost two times the effect of seizure control and six times the effect of MRI abnormality. Poorest QOL was noted in patients with DRE with AS, followed by those with WCE with AS, DRE without AS, and WCE without AS. CONCLUSION: The major determinant of QOL in patients with epilepsy is AS rather than DRE or WCE status. PMID- 20591745 TI - Sequential analyses of daily symptoms in women with fibromyalgia syndrome. AB - Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder characterized by generalized pain, chronic fatigue, sleep disturbance, and a range of other symptoms having no definitive pathology. Consequently, patient evaluations rely on self-report. Ecological Momentary Assessment (EMA) allows frequent real-time collection of self-report measures, removing recall bias and increasing external validity. We studied 81 females with FMS aged 18 to 42 years. Participants carried EMA devices (Palm Pilot M100) programmed to request ratings to 8 FMS symptoms/conditions 3 times daily for 30 days. Completeness of response rates varied across participants and over time. Controlling for immediately previous fatigue (ie, fatigue rating from the immediately preceding rating), unit increases in immediately previous pain and immediately previous emotional distress predicted 9 and 7% increases, respectively, in current fatigue. Controlling for immediately previous emotional distress, a unit increase in immediately previous pain predicted 7% increase in current emotional distress. Controlled for immediately previous pain, a unit increase in immediately previous fatigue predicted a 7% increase in current pain, enhanced by prior diurnal effects; immediately previous emotional distress was not significant. Collectively these results suggest an asymmetry in which emotional stress and pain may increase fatigue, fatigue but not emotional distress may increase pain, and pain but not fatigue may increase emotional distress. Despite small effects and person-to-person variability, these findings suggest that longitudinal data collection by EMA may reveal sequential or causal explanatory patterns with important clinical implications. PERSPECTIVE: Understanding how multiple symptoms covary in FMS is essential for optimal treatment planning. Our results show small but significant temporal relations among pain, fatigue, and emotional distress. Our results also provide support for the use of EMA as a viable data collection method that allows longitudinal, real-time assessment of multiple FMS symptoms. PMID- 20591746 TI - Normal pupil findings can give a false sense of security in a presumed cranial nerve III palsy patient: A unique case report. AB - BACKGROUND: A cranial nerve (CN) III palsy can be caused by a life-threatening aneurysm, typically of the posterior communicating artery. The "rule of the pupil" states the majority (96%) of such cases will present with abnormal pupil findings caused by compression of the fibers, located superficially along CN III. Careful examination of the size and reactivity of the pupils is critical. CASE REPORT: This case describes the complex management of a 79-year-old man with sudden-onset ptosis and diplopia consistent with a superior division CN III palsy. The pupils were normal, but because of the incomplete nature of the palsy the "rule of the pupil" could not be applied, and an aneurysm remained a threat. After urgent testing, microvascular infarct was deemed the cause. However, the palsy failed to resolve after 3 months. Further investigation found myasthenia gravis as the final diagnosis. CONCLUSIONS: Several important points are outlined regarding CN III palsies. First, lack of pupil involvement in an incomplete palsy is not equivalent to pupil sparing in a complete palsy. Second, after initial diagnosis, if subsequent findings are no longer consistent, further investigation is warranted. Lastly, myasthenia gravis should be considered as a differential in apparent palsy cases. PMID- 20591747 TI - Coping strategies to manage stress related to vision loss and fluctuations in retinitis pigmentosa. AB - BACKGROUND: Vision loss in retinitis pigmentosa (RP) is a slowly progressive and inexorable threat to patients' independence. It is not surprising that RP patients, many of whom are young when diagnosed, are at high risk for stress related to their vision loss. To address these issues, eye care providers need to be aware of what coping strategies RP patients use to successfully manage their vision loss. METHODS: We held focus groups with 8 legally blind RP patients to help us better understand how they cope with the stress that is generated from their progressive vision loss and fluctuations in vision. Focus group sessions were audio-taped and resulting notes were coded using conventional qualitative analytic techniques. RESULTS: Two themes were identified: (1) "kicking and screaming" captured the ways in which RP patients fight to maintain their independence in the face of worsening vision; and (2) "there are so many worse things" describes how RP patients keep their vision loss in perspective. These RP patients demonstrated high levels of resiliency. In particular, they often used humor as a coping mechanism. CONCLUSION: Understanding the ways in which RP patients manage their gradual, impending vision loss may lead to improved quality of care for this patient population. PMID- 20591748 TI - Cross-linked hyaluronan gel improves the quality of life of prostate cancer patients undergoing radiotherapy. AB - PURPOSE: To test the hypothesis that cross-linked hyaluronan gel (Hylaform) does not affect the quality of life (QOL) of prostate cancer patients undergoing radiotherapy. METHODS AND MATERIALS: Thirty-five patients with early stage prostate cancer underwent high-dose-rate brachytherapy to 2200 cGy and intensity modulated radiation therapy to 5040 cGy on a prospective study. Thirty patients received a single transperineal injection of 9-mL Hylaform between the prostate and rectum under transrectal ultrasound guidance immediately before the start of radiotherapy. Hylaform increased the separation between the prostate and rectum by 6-19 mm (median, 13 mm) at the start of radiotherapy. Five patients did not receive Hylaform and served as controls. We assessed gastrointestinal-related QOL using Expanded Prostate Cancer Index Composite Bowel Bother scores immediately before the start of and during the last week of radiotherapy. RESULTS: At the beginning of intensity modulated radiation therapy, daily mean rectal doses were 74+/-8 cGy (mean+/-standard deviation) and 105+/-25 cGy (mean+/-standard deviation) with vs. without Hylaform, respectively (p=0.01). Expanded Prostate Cancer Index Composite Bowel Bother scores decreased by 0+/-3 (mean+/-standard deviation) and 11+/-14 (mean+/-standard deviation) in patients who did and did not receive Hylaform, respectively (p=0.03). CONCLUSIONS: Hylaform increased the separation between the prostate and rectum and decreased the mean rectal dose, thereby improving the gastrointestinal-related acute QOL of prostate cancer patients undergoing radiotherapy. Patients will be followed up long term to determine if the improvement in acute QOL also translates into an improvement in late QOL. PMID- 20591749 TI - Risk factors for uterine rupture after laparoscopic myomectomy. AB - Case reports for uterine rupture subsequent to laparoscopic myomectomy were reviewed to determine whether common causal factors could be identified. Published cases were identified via electronic searches of PubMed, Google Scholar, and hand searches of references, and unpublished cases were obtained via E-mail queries to the AAGL membership and AAGL Listserve participants. Nineteen cases of uterine rupture after laparoscopic myomectomy were identified. The removed myomas ranged in size from 1 through 11 cm (mean, 4.5 cm). Only 3 cases involved multilayered closure of uterine defects. Electrosurgery was used for hemostasis in all but 2 cases. No plausible contributing factor could be found in one case [corrected]. It seems reasonable for surgeons to adhere to techniques developed for abdominal myomectomy including limited use of electrosurgery and multilayered closure of the myometrium. Nevertheless, individual wound healing characteristics may predispose to uterine rupture. PMID- 20591751 TI - Evaluation of new affinity chromatography resins for polyclonal, oligoclonal and monoclonal antibody pharmaceuticals. AB - The performance of MabSelect SuRe and IgSelect affinity chromatography resins designed for process-scale purification of antibodies was investigated. Various antibodies (4 human monoclonal, 1 human polyclonal and 1 bovine polyclonal antibody and 1 Fc-fusion protein) were used to evaluate the elution pH and dynamic binding capacity of the resins. The elution pH for each human antibody was similar on MabSelect SuRe and IgSelect (pH 3.5-3.8). No significant differences in dynamic binding capacity were observed among human antibodies on MabSelect SuRe ( approximately 20-40 mg/mL resin) and IgSelect (approximately 10 30 mg/mL resin). The binding capacity order for the human antibodies was the same on MabSelect SuRe and IgSelect. Using a linear pH gradient, both resins were able to partially separate monomeric and aggregated forms of the antibodies. The results indicate that these new affinity resins are powerful tools for the purification of human polyclonal antibodies from transgenic animals and oligoclonal antibodies from CHO cell cultures. PMID- 20591752 TI - Determination of free and glucuronidated kaempferol in rat plasma by LC-MS/MS: application to pharmacokinetic study. AB - Flavanoid kaempferol is mainly present as glucuronides and sulfates in rat plasma, and small amounts of the intact aglycone are also detected. In the this study, a rapid, specific and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-MS/MS) was developed and validated for determination of kaempferol and its major metabolite glucuronidated kaempferol in rat plasma. A liquid-liquid extraction with acetic ether was involved for the extraction of kaempferol and internal standard. Analytes were separated on a C18 column (150 mm x 2.1 mm, 4.5 microm, Waters Corp.) with isocratic elution at a flow-rate of 0.3 ml min(-1). The mobile phase was consisted of 0.5% formic acid and acetonitrile (50:50, v/v). The Quattro Premier HPLC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique. The method was validated according to the FDA guidelines for validation of bioanalytical method. The validated method was successfully applied to the study of the pharmacokinetics in rats after oral administration of kaempferol with different doses. PMID- 20591753 TI - Preparation and recognition performance of creatinine-imprinted material prepared with novel surface-imprinting technique. AB - By adopting the novel surface molecular imprinting technique put forward by us not long ago, a creatinine molecule-imprinted material with high performance was prepared. The functional macromolecule polymethacrylic acid (PMAA) was first grafted on the surfaces of micron-sized silica gel particles in the manner of "grafting from" using 3-methacryloxypropyltrimethoxysilane (MPS) as intermedia, resulting in the grafted particles PMAA/SiO(2). Subsequently, the molecular imprinting was carried out towards the grafted macromolecule PMAA using creatinine as template and with ethylene glycol diglycidyl ether (EGGE) as crosslinker by right of the intermolecular hydrogen bonding and electrostatic interaction between the grafted PMAA and creatinine molecules. Finally, the creatinine-imprinted material MIP-PMAA/SiO(2) was obtained. The binding character of MIP-PMAA/SiO(2) for creatinine was investigated in depth with both batch and column methods and using N-hydroxysuccinimide and creatine as two contrast substances, whose chemical structures are similar to creatinine to a certain degree. The experimental results show that the surface-imprinted material MIP PMAA/SiO(2) has excellent binding affinity and high recognition selectivity for creatinine. Before imprinting, PMAA/SiO(2) particles nearly has not recognition selectivity for creatinine, and the selectivity coefficients of PMAA/SiO(2) for creatinine relative to N-hydroxysuccinimide and creatine are only 1.23 and 1.30, respectively. However, after imprinting, the selectivity coefficients of MIP PMAA/SiO(2) for creatinine in respect to N-hydroxysuccinimide and creatine are remarkably enhanced to 11.64 and 12.87, respectively, displaying the excellent recognition selectivity and binding affinity towards creatinine molecules. PMID- 20591754 TI - [Larva Currens as a differential diagnosis of skin lesions in immigrant children]. PMID- 20591756 TI - [Pyomyositis due to Salmonella enteritidis in an immunocompetent patient]. PMID- 20591757 TI - The microbiological basis for a revised antibiotic regimen in high-energy tibial fractures: preventing deep infections by nosocomial organisms. AB - BACKGROUND: Deep surgical site infections (SSI's) complicate Gustilo IIIB tibial fractures in 8-13% of cases. Antibiotic prophylaxis typically covers environmental contaminants. However, nosocomial organisms are usually implicated in deep infection. We used the microbiological profile of infected Gustilo IIIB tibial fractures to define a new, dynamic prophylactic regimen which recognises the need for prophylaxis against nosocomial organisms at the time of definitive closure. METHODS: The microbiological profiles of Gustilo IIIB tibial fractures presenting over a 2-year period from January 2006 to December 2007 were reviewed. The environmental contaminants were compared with the organisms isolated from deep SSI's and correlated with the prophylactic antibiotic regimen used. RESULTS: Fifty-two patients were included. Nine developed a deep tissue infection. The pathogens implicated included resistant Enterococci, Pseudomonas, Enterobacter and MRSA. Standard antibiotic prophylaxis provided cover for these combinations in only one of nine cases. This would have improved to eight of nine cases with the use of teicoplanin and gentamicin, given as a one-time dose during definitive soft-tissue closure. Specimens taken from wound debridement were neither sensitive nor specific for the subsequent development of deep infection and did not predict the organisms responsible. CONCLUSIONS: Following high-energy open fracture, a single prophylactic antibiotic regimen directed against environmental wound contaminants does not provide cover for the organisms responsible for deepest SSI's and may have depopulated the niche, promoting nosocomial contamination prior to definitive closure. We advocate a dynamic prophylactic strategy, tailoring a second wave of prophylaxis against nosocomial organisms at the time of definitive wound closure, and at the same time avoiding the potential complications of prolonged antibiotic use. PMID- 20591758 TI - Classification of convex nasal dorsum deformities in Asian patients and treatment outcomes. AB - BACKGROUND: A new classification system for dorsal humps in Korean patients with nasal dorsum deformities was designed. Patients were treated based on these classifications, and their treatment outcomes were assessed. METHODS: A total of 164 patients, who underwent rhinoplasty for correction of convex nasal dorsum deformities, were analysed. Convex dorsum deformities were classified based on anthropometric measurement, nasal length, hump length and tip projection. The three classifications were generalised hump, isolated hump and relative hump because of a low tip. Postoperative photographs were analysed to assess hump reduction outcomes. RESULTS: Generalised hump was the most common deformity, occurring in 88 (53.7%) patients; an isolated hump was observed in 67 (40.9%) patients and a relative hump, with a low tip, was observed in nine (5.5%) patients. Successful surgical outcomes were achieved in 65.9% of generalised hump cases and 80.6% of isolated hump cases (p=0.014). Of the fair or poor outcomes, 89.6% were attributable to hump undercorrection. CONCLUSION: Our classification system could help surgeons tailor management of convex nasal dorsum deformities. The present study showed that the milder the deformity, the better was the outcome. It was also found that excessive conservation in hump reduction was the main factor predictive of unsatisfactory outcome. PMID- 20591759 TI - Clinical outcomes of patients with prominent nasolabial folds corrected by the technique: dermo-fascial detachment and fat grafting. AB - BACKGROUND: Prominent nasolabial folds (NLFs) due to ageing are a major aesthetic concern among Asian women. The main causes are drooping of the cheek mass, depressions (folds) and dermal attachments. We have conducted a study to analyse the long-term outcomes of the conventional dermo-fascial detachment and fat grafting technique. METHODS: A total of 209 patients with NLFs of different severity were included in the study. Dermo-fascial detachment was used to completely dissect the attachments; then, the space was filled with fat grafts. The outcomes and related factors were analysed statistically based on the classification of NLF grades. RESULTS: The average operating time was 28.4 min, and no postoperative infections were found. A high improvement ratio was noted: at the 3-month, 1-year and 2-year follow-up consultations; the improvement ratio was about 100%, 97.4+/-2.6% and 66.7+/-9.2%, respectively. At the 2-year follow up, the improvement ratio of the severe grade group (71.4+/-10.1%) remained higher than that of the mild grade group (50.0+/-22.3%). Six cases relapsed to the original grade (15.4%), and two cases were worse after 2 years (5.1%). No statistical correlation between age and the grade of the condition was determined (p=0.746). Total filling amounts with fat grafts made no statistical difference to the outcomes of the long-lasting group (1.93+/-0.26 cc) and the non-long lasting group (1.84+/-0.19 cc) (p=0.435). CONCLUSION: Dermo-fascial detachment and fat grafting is a safe and reliable technique for the correction of prominent NLFs with high improvement ratios, minimal morbidities and long-lasting outcomes. PMID- 20591760 TI - Diabetes, physical activity and breast cancer among Hispanic women. AB - PURPOSE: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. METHODS: We used data from a case-control study of breast cancer among Hispanic women aged 30-79 conducted between 2003 and 2008 on the Texas Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n=511) and low-risk (N=468) for breast cancer (with respective response rates of 97%, 83% and 74%). RESULTS: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71-1.48; low-risk control group OR 0.87, 0.58-1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63-1.48) or a slightly reduced breast cancer risk (low risk control group OR 0.72, 95% CI 0.46-1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21-0.83) regardless of the control group used (high-risk control group p-value for interaction=0.013, low-risk control group p value for interaction 0.183). CONCLUSIONS: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women. PMID- 20591761 TI - Effect of occlusal splint treatment on the temperature of different muscles in patients with TMD. AB - PURPOSE: The aim of this study was to evaluate the effect of occlusal splint treatment on the temperature of masseter (inferior, intermediate and superior), anterior temporal, digastric and trapezius muscles in patients with temporomandibular disorder (TMD). MATERIALS AND METHODS: Thirty patients (6 male and 24 female) aged from 16 to 57 years (mean 37.8+/-11.4 years) were selected. The patients were diagnosed with muscular TMD by clinical examination (application of Research Diagnostic Criteria questionnaire and physical examination). Occlusal splints in acrylic resin were inserted in all patients with a weekly follow-up. The superficial thermography ( degrees C) on the both sides of the muscles was performed using a digital thermometer in a controlled temperature room. This procedure was performed before occlusal splint insertion (patient with pain) and after the completion of the treatment (patient without pain). The data were analyzed by 2-way repeated-measures ANOVA and means were compared by Tukey HSD test (P<.05). RESULTS: After occlusal splint treatment a significant increase in temperature was observed in each muscle, both in the right and left sides. When the muscles were compared in the same period (before or after therapy) there was no significant difference among them. CONCLUSION: It can be concluded that the use of occlusal splint promoted a significant increase on the muscles temperature. There was symmetry in the temperature of muscles on the right and left sides both before and after the treatment. PMID- 20591762 TI - Comprehensive treatment in a case with advanced chronic periodontitis: a 15-year follow-up. AB - This case report describes the comprehensive treatment of generalized, advanced periodontal disease and full-mouth rehabilitation in an adult patient. Given the extensive periodontal tissue destruction, a systematic approach was needed to determine restoration possibilities and patient expectations. Subsequent oral rehabilitation was accomplished with fixed dentures in the mandible and a removable denture in the maxilla. In the maxilla, strategically important anchor teeth were replaced with implants and a palate-free horseshoe-shaped removable denture was fabricated, using telescopic crowns as abutments. This case indicates that long-term post-treatment periodontal stability can be ensured only by full patient cooperation and consistent periodontal maintenance. PMID- 20591763 TI - A dual-laminate snore reduction appliance: a report of four cases. AB - This article describes a snore reduction appliance that can be constructed to advance and hold the mandible in a comfortable prognathic position. The tongue is advanced concomitantly, producing more space in the pharynx while changing the relative positions of the soft palate, posterior tongue, and pharyngeal walls to reduce the incidence of snoring and ameliorate sleep apnea. A dual-laminate appliance, soft inside and hard outside, is vacuformfitted to casts of the maxillary and mandibular teeth and luted in a protrusive relation with cold pressure-cured acrylic. The appliance maintains the mandible and tongue in a protrusive position to open the upper airway, reducing snoring and facilitating breathing. Edentulous patients would require implant-retained appliances for appropriate retention and stability. PMID- 20591764 TI - How light sources and distance of the light tip influence water sorption, solubility, and biaxial flexural strength of a composite resin. AB - This study evaluated the water sorption (WS), solubility (SL), and biaxial flexural strength (BFS) of a resin composite based on different polymerization units, storage permeants (distilled water and 75% ethanol), and distances between the light's tip and the composite resin. Using a stainless steel mold, 80 specimens were made and separated in two independent groups, according to the duration of storage (7 days or 60 days). The specimens were photocured using either a QTH or LED light (both used at 600 mW/cm2 for 40 seconds), with the light's tip guide either 0 mm or 2 mm from the surface of the resin. In general, the 75% ethanol produced higher WS and SL values but lower BFS values compared to water. Both distances influenced the WS and SL values, especially when 75% ethanol was used (p < 0.05), although neither distance affected BFS values (p > 0.05). For nearly all groups, the WS, SL, and BFS in different solvents and at different distances for photocuring of the tested resin were not affected by the curing light used. PMID- 20591765 TI - Correction of nonparallel implants for an implant-retained overdenture. AB - An implant-retained overdenture is less expensive than a fixed implant-retained prosthesis; however, using ball attachments on abutments that are nonparallel and/or outside the path of insertion may result in loss of retention. As described in this case report, alignment devices can be used as a mandibular overdenture retainer to diminish the lack of parallelism between two implants. The treatment plan involved the use of an alignment device on each implant to ensure correct alignment among ball attachments and its retentive component. These devices can be used to fabricate overdentures retained by implants that are misaligned by as much as 14 degrees. PMID- 20591766 TI - A simple device for positioning intraoral x-ray sensors. AB - This article describes a simple technique for positioning an intraoral x-ray sensor in patients who are undergoing procedures such as endodontic treatment or post fitting for a crown. By placing a wooden tongue depressor and sensor inside an infection control barrier, the patient is able to hold the sensor comfortably in position without removing the rubber dam clamp, while the patient's fingers are kept out of the path of the x-ray beam. PMID- 20591767 TI - Effects of 3% sodium ascorbyl phosphate on the hardness and bond strength of human enamel bleached with 10% carbamide peroxide. AB - For this study, 120 fragments obtained from human third molars were randomly separated into 12 groups (n = 10). Four groups were used for measuring the Knoop hardness number (KHN) of enamel, while the other eight were used for testing the microtensile bond strength (muTBS) of two adhesive systems (Single Bond and Prime & Bond NT). All groups presented statistically similar KHN values. According to bond strength results, bleached enamel without antioxidant application demonstrated the lowest values of all groups. Based on these results, it could be concluded that the bleaching agents used in the present study (with or without sodium ascorbyl phosphate) did not affect human enamel hardness and that sodium ascorbyl phosphate is able to reverse the compromised bonding in bleached human enamel. PMID- 20591768 TI - Establishing a stable centric position using overlays. AB - The masticatory system's ability to function depends on the distribution of occlusal contacts to promote mandibular stabilization. The patient in this case report was experiencing temporomandibular dysfunction, which was treated by creating an adequate bite plane using indirect composite resin restorations (overlays) made from a wax-up. This therapy made it possible to improve esthetics as well as centric and excursive mandibular occlusion without the need for drilling. PMID- 20591770 TI - FDA new drug approvals in 2009. PMID- 20591771 TI - The use of pink porcelain for gingival defects in restorative dentistry: a case report. PMID- 20591772 TI - Composites: choices that fit your patients. PMID- 20591773 TI - Appropriate analgesic prescribing for the general dentist. AB - This article reviews dental and medical literature pertaining to the safety, efficacy, and mechanisms of action of common analgesic treatments for acute postoperative pain. MEDLINE searches were conducted for 2005 through 2009 using the terms "dental analgesia," "postoperative pain," "pain medication," "pathophysiology," "treatment," and "dentistry." Reports selected for further review included those published in peer-reviewed journals. The authors gave preference to articles reporting randomized controlled trials. Acetaminophen and NSAIDs continue to be the most appropriate choices for the treatment of mild to moderate acute dental pain. The use of selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs may be considered for patients at risk of gastrointestinal sequelae or those taking blood thinners such as warfarin. Whether analgesic medications are used alone or in combination, prescribers must be aware of the potential safety concerns associated with them, especially in light of new information promoting lower doses, shorter treatment durations, and decreased maximum recommended doses. PMID- 20591774 TI - Topographical evaluation of different glass and quartz fiber post surface treatments by a tridimensional surface roughness test. AB - A tridimensional surface roughness test evaluation is a nondestructive method that can be used to perform a topographic analysis of different surface treatments for glass and quartz fiber posts. This study divided 75 fiber posts into three groups according to their manufacturer. Each group was divided into five subgroups (n = 5), according to the surface treatment each received: immersion in hydrofluoric acid, sandblasting, immersion in hydrogen peroxide, sandblasting followed by immersion in hydrofluoric acid, or sandblasting followed by immersion in hydrogen peroxide. Surface roughness was measured using a tridimensional surface roughness test and analyzed with three-dimensional analysis software. Results were statistically analyzed using Student's t-test. The only surface treatment to modify the surface topography of glass and quartz fiber posts and provide a significant increase in roughness was sandblasting airborne-particle abrasion with 50 micro alumina at a distance of 30 mm, using 2.5 bars of pressure for five seconds. PMID- 20591775 TI - A core fracture with all-ceramic crowns: a case report. AB - This article is an observational-descriptive type case study with references to recent literature on ceramic fracture. The case selected was an unusual incidence of a veneer-to-core fracture of a Procera AllCeram crown after 18 months of service. This unusual case represents a significant concern to general dentists, because the highly dense alumina core is supposed to show comparable fracture resistance to the metal cores of conventional metal-ceramic crowns. Clinical evidence shows that bruxism, manufacturing defects, pre-cementation occlusal adjustment by the laboratory technician or dentist, and the cement used are factors that contribute to the fracture of ceramic cores. PMID- 20591776 TI - A review of oro-antral communications. AB - Oro-antral communications are occasionally produced during routine oral surgery procedures and often cannot be avoided. Dentistry's emphasis on implantology means that defects in the maxillary sinus are encountered far more frequently than before; therefore, knowledge of the maxillary sinus is of the utmost importance. Unfortunately, many general dentists have not been trained to provide proper treatment to correct these defects. Swift diagnosis and subsequent treatment are vital to proper and successful management. This article reviews the literature and the anatomy of the maxillary sinus and discusses the diagnosis and conservative treatment of oro-antral communications. PMID- 20591777 TI - Smoking cessation in the dental setting: a practical approach. AB - Smoking is a prevalent behavior with severe health consequences. Various smoking cessation methods that are available to dentists include nicotine replacement therapies, other pharmacological agents, and biobehavioral therapies. This article presents a smoking cessation protocol that can be carried out as part of routine oral care. PMID- 20591778 TI - Cigarette smoke affects bonding to dentin. AB - This in vitro study evaluated the microtensile bond strength (muTBS) of composite resin bonded to dentin that had been contaminated by cigarette smoke. Ten extracted unerupted human third molars were used: Six molars were prepared for muTBS testing, while the other four molars were assigned to pre- and post-etching scanning electronic microscopy (SEM) analysis. The 20 specimens obtained from the 10 coronal portions were distributed into two experimental groups so that each tooth served as its own control. Group 1 underwent a daily toothbrushing simulation and exposure to a smoking simulation chamber, while Group 2 received only a daily simulated toothbrushing. Student's t-test demonstrated that Group 1 samples demonstrated significantly lower bond strength (49.58 MPa) than Group 2 samples (58.48 MPa). Pre and postetching SEM analysis revealed the presence of contaminants on the dentinal surfaces of the Group 1 specimens. It was concluded that contamination by cigarette smoke decreases the bond strength between dentin and composite resin. PMID- 20591779 TI - Effect of surface sealant and repolishing procedures on the color of composite resin exposed to cigarette smoke. AB - This study evaluated the effect of cigarette smoke on the color of composite resins, with and without the application of a surface sealant and before and after the restorative material was repolished. Twenty composite resin specimens were divided into two groups (n = 10); one of which received a surface sealant. Both groups were exposed daily to the smoke of 20 cigarettes. Color analyses were performed using a spectrophotometer at different intervals: prior to cigarette smoke exposure (baseline), 21 days after cigarette smoke exposure, and after the specimens were repolished using aluminum oxide discs. Cigarette smoke caused a decrease in lightness (L*), especially in samples that received the sealant (p = 0.014). At 21 days, there was an increase in yellow pigment for both groups, with higher values (p = 0.00001) and predominant red pigmentation in the samples that received sealant. An increase in lightness and a decrease in yellow pigments (p < 0.05) were reported in both groups after repolishing. Cigarette smoke significantly altered the color of the composite resin (DeltaE > or = 10.34), especially in the specimens that received the sealant. In this study, the sealant tested intensified cigarette staining, and although repolishing decreased surface pigmentation, it was unable to restore the original color of the composite resin. PMID- 20591780 TI - Oral ulceration due to chronic use of Nicorette gum: case report. AB - Oral ulceration is a common presentation in a dental clinic. These ulcers may be acute or chronic, based on the duration of symptoms. The etiology of oral ulceration can range from trauma to squamous cell carcinoma. It is the responsibility of the dentist to differentiate the various etiologies of oral ulceration for proper management. This case report is presented to remind dentists that the long-term use of Nicorette gum should be considered in the differential diagnosis of chronic oral ulcers. PMID- 20591781 TI - Clinical evaluation of two packable resin-based composite restorations: a three year report. AB - This randomized clinical trial sought to evaluate the performance of two packable composites over a period of 36 months. A total of 39 Class I and II restorations were placed in the permanent teeth of 20 patients. Using United States Public Health Services criteria, two investigators evaluated the restorations immediately after placement and again after 12 and 36 months, examining color match, marginal discoloration, marginal integrity, recurrent caries, proximal contact, anatomical shape, surface texture, and postoperative sensitivity. It was concluded that the packable composites evaluated showed satisfactory clinical performance after three years. PMID- 20591782 TI - Gingival mass. Congenital epulis. PMID- 20591783 TI - Tongue nodule. Granular cell tumor. PMID- 20591784 TI - [Pathogenesis of adrenocortical cancer]. AB - Adrenocortical cancer is a rare tumor with poor prognosis. Whereas most cases occur in a sporadic setting, there are very rare hereditary forms that are important for the understanding of tumor pathogenesis. The hereditary syndromes associated with adrenocortical cancer are: Li-Fraumeni's syndrome, Beckwith Wiedemann's syndrome and familial adenomatous polyposis, whereas multiple endocrine neoplasia type 1, Carney's complex and McCune-Albright's syndrome mostly predispose to benign adrenocortical tumors. Overexpression of insulin like growth factor 2, activation of Wnt/beta-catenin and cAMP-protein kinase A signaling, as well as mutations of p53 and MEN1 genes are regarded as major pathogenetic mechanisms. Options for medical treatment of adrenocortical cancer are rather limited. Recently published molecular-bioinformatical studies have revealed several previously unknown pathogenetic pathways that may even represent potential drug targets. In this study, the pathogenesis of hereditary tumor syndromes, the alterations in sporadic tumors and the most recent molecular bioinformatical observations are discussed. PMID- 20591785 TI - [Biomarkers in lupus nephritis]. AB - Systemic lupus erythematosus is a polysystemic autoimmune disease. One of the most common and serious complication is lupus nephritis. Notification of these complications before organic disorder, prediction of flares, starting aggressive therapy as early as possible, and the follow-up of successful treatment would be desirable. There is an intensive need for identifying the best biomarker for monitoring flare activity. The goal of this review is to present not only the most frequently ordered serologic tests, but the latest, partly experimental biomarkers reflecting flares, which are not used in clinical practice. Biomarkers used specifically in lupus nephritis are also described. PMID- 20591786 TI - [Combined interferon, ribavirin treatment and the occurrence of hepatocellular carcinoma]. AB - Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer-related death worldwide. Primary hepatocellular carcinoma can be found most frequently (80-90%) in patients with liver cirrhosis. The most frequent causes of liver cirrhosis are chronic hepatitis B and C virus infections and chronic alcohol consumption. The treatment and elimination of the etiological factors decreases the risk of HCC. The authors summarize the literary data, where effect of modern antiviral treatment has been examined according to the occurrence of HCC. It can be stated, that the antiviral therapy (interferon and nucleoside analogues) is able to decrease the risk of HCC or the recurrence of the tumor after curative treatment of HCC, in case of non responder state, as well. Drugs used for the insurance of equilibrium in redox state can also help in the decrease of HCC risk. PMID- 20591787 TI - [Amyloidosis]. AB - The term amyloidosis refers to the extracellular deposition of fibrils composed of different types of plasma proteins. Various clinical symptoms are caused by the tissue damage related to the deposited fibrillary material. Except of the brain, all organs can be affected: kidney, liver, spleen, lung, gastrointestinal tract, endocrine organs, skin, heart and autonomous nervous system. Diagnosis is confirmed by specific histological methods (congo red stain, polarized and electron microscopy, immunohistochemistry) and genetic testing. Scintigraphy with radioisotope labeled serum amyloid P-component is helpful in the localization of the process and in the assessment of therapeutic effect. In the majority of cases the underlying disease is a plasma cell disorder, light chains aggregate to amyloid fibrils. Therefore chemotherapy and - in selected patients - stem cell transplantation is the choice of treatment. Another common type of amyloidosis is caused by chronic inflammatory diseases (amyloid fibrils are composed of elevated serum amyloid A being related to C reactive protein), or by some hereditary fever syndromes. Treatment of the underlying disorder may bring resolution of the amyloid burden. In 10% of the cases, amyloid fibrils are composed of genetically modified proteins. Depending on the source of the mutant protein liver transplantation, hepatorenal or cardiorenal transplantation may cure the disease. PMID- 20591788 TI - [Ornithosis--case report and current concerns]. AB - The authors describe a severe case of psittacosis requiring intensive care, and summarize the potential means of diagnosis, as well as the epidemiologic and therapeutic aspects of the disease. Clinical signs of ornithosis do not allow a reliable differentiation from other atypical bacterial infections, thus, exploring the possible exposure to birds in the patient's history is most important in these cases. Knowledge of bird exposure in the history leads the clinician to the correct diagnosis that may result quick recovery due to the adequate therapy. This notifiable disease may presumably belong to the misdiagnosed or delayed diagnosed infections even today so the underrepresented case-reports do not necessarily reflect the actual epidemiological situation in Hungary. The aim of the authors was to call the attention to this sometimes fatal disease occurring not as rarely as supposed. PMID- 20591789 TI - [Farewell to prof. Janos Feher (1932-2010)]. PMID- 20591791 TI - Learned resourcefulness, quality of life, and depressive symptoms for patients with breast cancer. AB - PURPOSE/OBJECTIVES: To investigate the relationships among learned resourcefulness, quality of life, and depressive symptoms of women with breast cancer. In addition, the direct and indirect effects of learned resourcefulness among disease characteristics and quality of life and depressive symptoms were examined. DESIGN: Descriptive, correlational, and predictive. SETTING: Two teaching hospitals in southern Taiwan. SAMPLE: 150 women with breast cancer. METHODS: Participants completed demographic information concerning disease characteristics and learned resourcefulness via the Center for Epidemiological Studies-Depression questionnaire and the SF-36 health survey during visits to the outpatient oncology department. MAIN RESEARCH VARIABLES: Learned resourcefulness, depressive symptoms, and quality of life. FINDINGS: About 35% of the participants had depressive symptoms. Participants with lower income and those undergoing adjuvant therapy displayed more depressive symptoms. Learned resourcefulness was a strong predictor of depressive symptoms and quality of life, but no mediating effects of resourcefulness on depressive symptoms existed. In addition, when participants had better income and were at a lower stage, a better quality of life was evident. CONCLUSIONS: A high amount of patients with breast cancer experience depressive symptoms. Learned resourcefulness can be a method of helping patients to improve their self-control behaviors and change their negative thoughts. IMPLICATIONS FOR NURSING: Nurses and healthcare professionals can apply resourcefulness strategies to promote quality of life and to prevent depressive symptoms in women with breast cancer. PMID- 20591792 TI - Cervical cancer screening among Taiwanese women: a transtheoretical approach. AB - PURPOSE/OBJECTIVES: To assess Papanicolaou (Pap) test screening behaviors of Taiwanese women, to explore factors affecting stages of change, and to determine whether constructs from the transtheoretical model are applicable to Taiwanese women with regard to Pap screening. DESIGN: Descriptive, cross-sectional. SETTING: A hospital in Taiwan. SAMPLE: 222 female hospital workers. METHODS: Data were collected with a questionnaire. MAIN RESEARCH VARIABLES: Cervical screening behavior, perceived barriers and benefits, self-efficacy, and stages of change. FINDINGS: Fifty-six percent of participants reported engaging in regular screening practice. The stage of respondents' cervical cancer screening was significantly associated with age, marital status, and history of human papilloma virus-positive and abnormal tests. Self-efficacy scores were significantly higher for women who were in action or maintenance than those in precontemplation or relapse (p < 0.0001). Women in relapse reported significantly more perceived barriers than those in action-maintenance (p = 0.005). No significant differences were found in the level of perceived benefits (p = 0.702) to regular Pap screening among women in the various stages. CONCLUSIONS: Pap screening was low among the entire sample and nonexistent among women younger than age 30. The transtheoretical model only was partially applicable to the Taiwanese women in this study. IMPLICATIONS FOR NURSING: Reinforcement of self-efficacy was more important for women in the sample than emphasizing the benefits of or decreasing the barriers to regular Pap screening. Strategies for younger unmarried women might include education programs emphasizing the importance of routine annual screening and enhancing women's understanding of the relationship between Pap tests and cervical cancer. PMID- 20591793 TI - Health-related quality of life in women with breast cancer in Korea: do sociodemographic characteristics and time since diagnosis make a difference? AB - PURPOSE/OBJECTIVES: To describe whether levels of health-related quality of life (HRQOL) differ by sociodemographic characteristics and time since breast cancer diagnosis in women in Korea. DESIGN: A descriptive, cross-sectional study of women with breast cancer. SETTING: An outpatient clinic of one large hospital in Seoul, Republic of Korea. SAMPLE: A convenience sample of 244 women with breast cancer after mastectomy. METHODS: Study participants completed sociodemographic characteristics and HRQOL questionnaires. Medical charts were reviewed to determine time since breast cancer diagnosis. MAIN RESEARCH VARIABLES: Sociodemographic characteristics (age, marital status, employment status, education, monthly household income, and religion), time since diagnosis, and HRQOL. FINDINGS: The psychological well-being domain scored the lowest among domains of HRQOL. Women who are younger, married, unemployed, highly educated, or religious, with higher monthly household income or with greater than one year elapsed time since diagnosis, had higher HRQOL. CONCLUSIONS: Study findings will be useful to establish priorities in planning nursing interventions to enhance HRQOL in care of women with breast cancer. IMPLICATIONS FOR NURSING: Nursing interventions can be provided to Korean women with breast cancer who are not religious, who are older, single or widowed, or employed, with lower education level, with lower monthly household income, or with one year or less elapsed time since breast cancer diagnosis. PMID- 20591794 TI - Pediatric oncology: the use of cluster analysis to examine maternal concerns. AB - PURPOSE/OBJECTIVES: To examine data from mothers whose children have cancer and to identify the characteristics of uncertainty and distress that they reported. The objectives were (a) to use cluster analysis to identify subgroups of maternal uncertainty and distress, (b) to examine whether the subgroups differed based on demographics and children's illness-related variables, and (c) to explore whether mothers in the subgroups differed on quality of life (QOL) and hope. DESIGN: Descriptive, correlational study. SETTING: Pediatric oncology units in northern Taiwan. SAMPLE: 200 mothers of children with cancer. METHODS: Participants completed the Parental Perception of Uncertainty Scale, the Symptom Checklist-35 Revised, the Short-Form 36 Health Survey, the Herth Hope Index, and a demographic questionnaire. Cluster analyses were used to identify subgroups of mothers regarding maternal perceived uncertainty and distress. Differences in demographic variables, disease characteristics, and outcome measures were evaluated with descriptive statistics, analysis of variance, and chi-square analysis. MAIN RESEARCH VARIABLES: Subgroup, maternal uncertainty, distress, QOL, and hope. FINDINGS: Four subgroups were identified by the cluster analyses: high uncertainty and high distress, moderate uncertainty and moderate distress, low uncertainty and low distress, and high uncertainty and low distress. CONCLUSIONS: The subgroup of mothers who reported low uncertainty and low distress reported the highest QOL and hope. IMPLICATIONS FOR NURSING: The findings of this study provide insight for pediatric oncology clinicians and offer issues related to uncertainty, distress, and QOL that such professionals can discuss with the mothers of their patients. PMID- 20591795 TI - A community peer-volunteer telephone reminder call to increase breast cancer screening attendance. AB - PURPOSE/OBJECTIVES: To assess the effect of a tailored telephone reminder call by community peer volunteers on mammography rates in women who do not attend a breast cancer-screening program. DESIGN: Individual-level randomized trial. SETTING: Four semirural communities in Belgium. SAMPLE: Women aged 50-69 years who had not had a mammogram. METHODS: Women in the usual care (control) arm received an invitation letter for screening mammography and an information leaflet; women in the intervention arm received usual care as well as a telephone reminder call. The call was tailored on four variables: individual mammography history, mailing of the invitation letter, mammography appointment date, and type of mammography facility in the area (e.g., mobile unit versus fixed site). Community peer volunteers made up to three attempts to call the women in the intervention arm. MAIN RESEARCH VARIABLES: Mammography rates verified by screening registration review and adverse events identified in contacts with peer volunteers, radiologists, and community workers of local authorities. FINDINGS: A total of 3,880 women were included in the study and individually randomized into control and intervention groups. Phone numbers were identified for 79% of the women in the intervention group, and 69% were contacted. Twenty-two percent had screening mammography, which was 4% higher than controls (relative risk = 1.22). No adverse effects were identified. An additional mammogram came at an average cost of 17 phone conversations and two hours of volunteer work. CONCLUSIONS: The tested telephone reminder call is suitable for Belgian women. IMPLICATIONS FOR NURSING: The telephone reminder call may be implemented in settings similar to the studied context. PMID- 20591796 TI - Pain in children with central nervous system cancer: a review of the literature. AB - PURPOSE/OBJECTIVES: To explore the current state of the science regarding pain in children with cancer, with special attention to literature related to central nervous system (CNS) tumors. This review used the Human Response to Illness (HRTI) model as an organizing framework. DATA SOURCES: PubMed, CINAHL, and Scopus data-bases. DATA SYNTHESIS: The literature review is presented with the four components of the HRTI model, including the physiologic, pathophysiologic, experiential, and behavioral perspectives of the pain response related to childhood cancer and childhood CNS cancer. The person and environmental factors that may influence a child's pain response are described. CONCLUSIONS: Children with cancer, including CNS cancer, continue to experience pain despite the improvements in knowledge related to pain. Pain assessment and management strategies must continue to evolve and improve for nursing professionals to provide a high level of care to this patient population. The HRTI model provides an appropriate framework to gain insight into the pediatric oncology nursing role in the assessment, management, and evaluation of pain from childhood cancers. IMPLICATIONS FOR NURSING: Nurses play a vital role in pain assessment and management for children with cancer. The HRTI model can be used to identify areas of clinical practice, education, and research that require further improvements in relation to pain in children with CNS cancer. PMID- 20591797 TI - Congratulations and welcome to the world of oncology nursing. PMID- 20591798 TI - Direct-to-consumer marketing of genetic and genomic tests. PMID- 20591800 TI - The future of oncology nursing science: who will generate the knowledge? PMID- 20591801 TI - Prolonged grief disorder. PMID- 20591803 TI - Patients' perceptions of the importance of nurses' knowledge about cancer and its treatment for quality nursing care. AB - PURPOSE/OBJECTIVES: To gain insight into how and why patients' perceptions of nurses' knowledge about cancer and its treatments relate to quality nursing care. DESIGN: Qualitative study inspired by Giorgi's approach to phenomenology. SETTING: An oncology ward in a regional hospital in Norway. SAMPLE: 20 patients (10 women and 10 men). Most received life-prolonging and symptom-relieving treatment, whereas 4 had the possibility of being cured. METHODS: In-depth interviews were tape recorded, transcribed, and analyzed. The text was read as a whole, condensed into units of meaning, and clustered into themes of importance. Finally, the consistency between identified themes and the general structure of the interviews was checked. FINDINGS: Patients regarded knowledge about cancer and its treatment as basic in nursing and took for granted that nurses had this competency. Three themes were identified that explained why the knowledge was important: (a) it makes patients feel safe and secure and alleviates suffering by providing useful information, (b) it prevents and alleviates suffering and insecurity during chemotherapy, and (c) it alleviates suffering by relieving side effects caused by the treatment and symptoms caused by the disease. CONCLUSIONS: Patients appreciated meeting nurses who had experience and could combine clinical and biologic knowledge and nursing skills with a human touch. In addition, nurses alleviated patients' bodily and existential suffering and made them feel safe and secure. IMPLICATIONS FOR NURSING: Experienced, effective nurses with knowledge about cancer and its treatments are needed in oncology wards to provide optimal care to patients. PMID- 20591802 TI - Predictors of the trajectories of self-reported attentional fatigue in women with breast cancer undergoing radiation therapy. AB - PURPOSE/OBJECTIVES: To examine how attentional fatigue changed from the time of simulation to four months after the completion of radiation therapy and to investigate whether specific variables predicted initial levels and trajectories of attentional fatigue. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments. SAMPLE: 73 women with breast cancer who received primary or adjuvant radiation therapy. METHODS: Participants completed questionnaires prior to, during, and after radiation therapy. Descriptive statistics and hierarchical linear modeling were used for data analysis. MAIN RESEARCH VARIABLES: Attentional fatigue; demographic, clinical, and symptom characteristics. FINDINGS: Large amounts of interindividual variability were found in the trajectories of attentional fatigue. At baseline, higher levels of attentional fatigue were associated with younger age, not working, a higher number of comorbidities, and higher levels of trait anxiety. The trajectory of attentional fatigue improved over time for women with higher body mass index at baseline. CONCLUSIONS: This study is the first to identify predictors of interindividual variability in attentional fatigue in women with breast cancer undergoing radiation therapy. The predictors should be considered in the design of future correlational and interventional studies. IMPLICATIONS FOR NURSING: Nurses could use knowledge of the predictors to identify patients at risk for higher levels of attentional fatigue. In addition, nurses could use the information to educate patients about how attentional fatigue may change during and following radiation therapy for breast cancer. PMID- 20591804 TI - Patterns of fatigue in adolescents receiving chemotherapy. AB - PURPOSE/OBJECTIVES: To describe patterns of fatigue in adolescents and the impact of fatigue during one month of chemotherapy, to explore variables that affect fatigue, and to explore the feasibility of collecting daily self-report data in this population. DESIGN: Longitudinal, descriptive. SETTING: Two pediatric oncology centers in central Virginia. SAMPLE: 20 adolescents with a variety of cancer diagnoses receiving chemotherapy. METHODS: Adolescents described daily fatigue for one month using rating scales and qualitative diaries. MAIN RESEARCH VARIABLES: Fatigue severity. FINDINGS: Adolescents commonly reported a peak in fatigue in the days immediately following chemotherapy administration. The most common pattern for adolescents who received chemotherapy on a schedule every three to four weeks was a "declining rollercoaster" pattern, with fatigue severity alternating on a daily basis but gradually declining until chemotherapy was scheduled again. Adolescents who received chemotherapy weekly showed more frequent peaks and troughs (the "yo-yo" pattern) that did not diminish in severity over the weeks of the study. Adolescents associated fatigue with other symptoms, particularly sleep-wake disturbances, pain, and nausea, and frequently reported that fatigue interfered with daily activities. CONCLUSIONS: Fatigue commonly bothers adolescents receiving chemotherapy, particularly in the days following chemotherapy administration and when other symptoms are present. Although fatigue interfered with the adolescents' abilities to maintain their usual lifestyles, many still participated in the typical activities of adolescence. IMPLICATIONS FOR NURSING: Fatigue is a complex and dynamic symptom. Oncology clinicians and researchers should frequently assess fatigue in adolescents receiving chemotherapy and apply timely and tailored interventions to match the factors that contribute to fatigue and influence fatigue severity. Management of fatigue during treatment will help adolescents stay involved in age related activities and meet developmental milestones. PMID- 20591805 TI - Sleep across chemotherapy treatment: a growing concern for women older than 50 with breast cancer. AB - PURPOSE/OBJECTIVES: To conduct a metasynthesis of human sleep studies that included women aged 50 years and older with breast cancer across chemotherapy treatment. DATA SOURCES: English publications were searched with the terms sleep and breast cancer via Ovid, PubMed, and EBSCO-host databases. Human studies that used sleep-specific instruments published from January 1974-May 2009 were included. Intervention studies also were included if they provided baseline sleep data. Studies that used quality-of-life or symptom instruments or in which patients were prescreened for insomnia were not included. DATA SYNTHESIS: 382 publications were found; 17 met inclusion criteria, and 3 additional studies were located from the literature on fatigue. Two articles reported on the same study, so a total of 19 studies were included in the review. In women with nonmetastatic breast cancer, subjective and objective sleep quality appear to be poor and nocturnal awakenings frequent across chemotherapy treatment. Daytime sleepiness increases in the active phase of chemotherapy, and insomnia symptoms are common before and following chemotherapy treatment. In women with recurrent or metastatic breast cancer, difficulty falling asleep, nocturnal awakenings, difficulty awakening, and daytime sleepiness are problematic at different points in chemotherapy treatment. CONCLUSIONS: Sleep for women, including those older than 50 years, appears to be impaired across chemotherapy treatment, although replication of findings is very limited. IMPLICATIONS FOR NURSING: Future research should investigate sleep in specific age and minority groups, include daytime sleep and sleepiness, and use standard sleep nomenclature and objective measures. PMID- 20591806 TI - The sequelae of anxiety in breast cancer: a human response to illness model. AB - PURPOSE/OBJECTIVES: To provide a critical review of the empirical literature on anxiety in women with breast cancer using the physiologic, pathophysiologic, behavior, and experiential perspectives of the Human Response to Illness (HRTI) Model. DATA SOURCES: Research articles, clinical articles, and Internet sources on breast cancer and anxiety. Literature sources included CINAHL, PubMed, and PsycINFO, incorporating English language reports through March 2009. DATA SYNTHESIS: Patients with breast cancer experience fluctuating levels of anxiety throughout their diagnosis and treatment trajectory. Anxiety may influence an individual's response to treatment, treatment decision making, and overall quality of life. CONCLUSIONS: Research consistently demonstrates that anxiety in patients with breast cancer can have a negative effect on patient outcomes. IMPLICATIONS FOR NURSING: The insight gained from exploring anxiety within the context of the four interrelated perspectives of the HRTI model fosters the provision of optimal care for patients suffering with anxiety throughout their breast cancer illness trajectory. PMID- 20591807 TI - Pilot study of cranial stimulation for symptom management in breast cancer. AB - PURPOSE/OBJECTIVES: To examine the feasibility, relationships among variables, and preliminary outcomes of a self-directed complementary modality, cranial electrical stimulation (CES), for symptom management in women receiving chemotherapy for breast cancer. DESIGN: Biobehavioral pilot feasibility study. SETTING: Two university-based cancer centers. SAMPLE: 36 women with stage I-IIIA breast cancer scheduled to receive chemotherapy. METHODS: Data were collected via interview, questionnaires, and interactive voice technology (IVR). Biomarkers were measured from a blood sample taken prior to the initial chemotherapy. MAIN RESEARCH VARIABLES: Symptoms of depression, anxiety, fatigue, pain, and sleep disturbances; biomarkers (proinflammatory cytokines interleukin-6, tumor necrosis factor alpha [TNF-alpha], interleukin-1 beta) and C-reactive protein [CRP]); and CES. FINDINGS: CES appears to be a safe and acceptable modality during chemotherapy. Recruitment and retention were adequate. IVR was associated with missing data. Symptoms of depression, anxiety, fatigue, and sleep disturbances were highly correlated with each other, and most symptoms were correlated with CRP at baseline. Depression and TNF-alpha had a positive, significant relationship. Levels of depression increased over time and trended toward less increase in the CES group; however, the differences among groups were not statistically significant. CONCLUSIONS: The data support the feasibility of CES. Further testing in larger samples is needed to examine the efficacy of CES for symptom management of multiple, concurrent symptoms and to further develop the biobehavioral framework. IMPLICATIONS FOR NURSING: Interventions that are effective at minimizing more than one target symptom are especially needed to provide optimal symptom management for women with breast cancer. PMID- 20591808 TI - Perceptions of support among older African American cancer survivors. AB - PURPOSE/OBJECTIVES: To explore the perceived social support needs among older adult African American cancer survivors. RESEARCH APPROACH: Qualitative design using grounded theory techniques. SETTING: Outpatient oncology clinics in the southeastern United States. PARTICIPANTS: Focus groups with 22 older adult African American cancer survivors. METHODOLOGIC APPROACH: Purposeful sampling technique was used to identify focus group participants. In-depth interviews were conducted and participants were interviewed until informational redundancy was achieved. MAIN RESEARCH VARIABLES: Social support needs of older adult African American patients with cancer. FINDINGS: Social support was influenced by (a) symptoms and treatment side effects, (b) perceptions of stigma and fears expressed by family and friends, (c) cultural beliefs about cancer, and (d) desires to lessen any burden or disruption to the lives of family and friends. Survivors navigated within and outside of their networks to get their social support needs met. In some instances, survivors socially withdrew from traditional sources of support for fear of being ostracized. Survivors also described feeling hurt, alone, and socially isolated when completely abandoned by friends. CONCLUSIONS: The support from family, friends, and fellow church members is important to positive outcomes among older African American cancer survivors. However, misconceptions, fears, and negative cultural beliefs persist within the African American community and negatively influence the social support available to this population. INTERPRETATION: Early identification of the factors that influence social support can facilitate strategies to improve outcomes and decrease health disparities among this population. PMID- 20591809 TI - Breast cancer survivors' perspectives of care practices in Western and alternative medicine. AB - PURPOSE/OBJECTIVES: To explore perspectives of breast cancer survivors about their care with Western medicine and alternative medicine. RESEARCH APPROACH: Qualitative, ethnonursing. SETTING: Cancer center in the midwestern region of the United States. PARTICIPANTS: 9 breast cancer survivors who had experienced health care involving Western medicine and alternative medicine. METHODOLOGIC APPROACH: Semistructured interviews were conducted to elicit each participant's perspective about care practices. Data were analyzed with an ethnonursing qualitative data analysis method. MAIN RESEARCH VARIABLES: Care practices in Western medicine and care practices in alternative medicine. FINDINGS: Western medicine was seen as traditional or mainstream treatment, whereas alternative medicine was seen as anything not involving hospitals and doctors or as complementary. Perceived outcomes from alternative therapies were coping with disease and treatment, holistic care, and emotional support, whereas perceived outcomes from Western medicine were negative things that they had to go through and as an instrument of God. Kinship, social, economical, educational, and belief factors influenced care practices. CONCLUSIONS: Care practices from alternative medicine or Western medicine vary for breast cancer survivors. Many factors influence their selection decisions about care practices. INTERPRETATION: Nurses should be concerned about what care practices mean to breast cancer survivors. Further research should be considered to evaluate the potential contribution of each factor to breast cancer survivors' decision making about care practices. PMID- 20591810 TI - Piloting a needs assessment to guide development of a survivorship program for a community cancer center. AB - PURPOSE/OBJECTIVES: To develop and pilot a survey to assess needs and distress of cancer survivors receiving care in a community cancer center. DESIGN: Descriptive, quantitative. SETTING: A community cancer center in the southeastern United States partnering with a local college of nursing faculty. SAMPLE: Convenience sample of 307 adult cancer survivors. METHODS: Voluntary completion of a modified survey of needs. MAIN RESEARCH VARIABLES: Cancer survivor needs and distress according to five subscales (physical effects, social issues, emotional aspects, spiritual issues, and other issues), age, and gender. FINDINGS: Patients on average reported experiencing more than 25 of 50 possible survivorship needs. Average distress scores associated with individual needs were low. The most frequently experienced needs were fatigue, fear of recurrence, and sleep disturbance. Middle-aged survivors experienced significantly greater need and distress across all subscales. CONCLUSIONS: Need and distress exist among adult cancer survivors receiving treatment and follow-up in community cancer care settings, with the middle-age phase of life creating unique barriers. Survey data may provide documentation of the multidimensional impact of cancer on quality of life and can help direct survivorship program development. IMPLICATIONS FOR NURSING: Nurses can address a barrier to survivorship care in community care settings by using the Pearlman-Mayo Survey of Needs to assess outcomes relevant to survivors. Partnership between community hospital RNs and college of nursing faculty may create local or regional solutions and serve as useful models for survivorship care. PMID- 20591813 TI - Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study. AB - The European Renal Best Practice (ERBP), which are issued by ERA-EDTA, are suggestions for clinical practice in areas in which evidence is lacking or weak, together with position statements on recently published randomized controlled trials, or on existing guidelines and recommendations. In 2009, the Anaemia Working Group of ERBP published its first position statement about the haemoglobin target to aim for with erythropoietin-stimulating agents (ESA) and on issues that were not covered by K-DOQI in 2006-07. This second position paper of the group follows the publication of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Study. This multi-centre, placebo-controlled trial compared cardiovascular and renal outcomes in 4038 patients with type 2 diabetes, chronic kidney disease not on dialysis, and anaemia who were randomized to complete anaemia correction (haemoglobin target of 13 g/dL using darbepoetin alpha) or placebo (with a haemoglobin rescue value of 9 g/dL). Following the findings of the TREAT study, the Anaemia Working Group of ERBP maintains its view that 'Hb values of 11-12 g/dL should be generally sought in the CKD population without intentionally exceeding 13 g/dL' and that the doses of ESA therapy to achieve the target haemoglobin should also be considered. More caution is suggested when treating anaemia with ESA therapy in patients with type 2 diabetes not undergoing dialysis (and probably in diabetics at all CKD stages). In those with ischaemic heart disease or with a previous history of stroke, possible benefits should be weighed up against an increased risk of stroke recurrence, when deciding which Hb level to aim for. These recommendations are not intended to represent a new guideline as they are not the result of a systematic review of the evidence. PMID- 20591814 TI - Are peritoneal calcifications in long-term peritoneal dialysis related to aortic calcifications and disturbances in mineral metabolism? AB - BACKGROUND: Peritoneal calcifications are associated with long-term peritoneal dialysis (PD). Case reports have suggested a relation with disturbances in mineral metabolism such as the presence of severe hyperparathyroidism. Our aim was to investigate whether relationships are present between peritoneal calcifications and aortic calcifications or disturbances in mineral metabolism in long-term PD patients. METHODS: We included all long-term PD patients (PD >= 4 years) in our centre from 1996 to 2008 who had undergone an abdominal computed tomographic (CT) scan. The scans were reviewed by two experienced radiologists in consensus. The presence or absence of peritoneal calcifications was scored, and a severity scoring system for abdominal aortic calcifications was used: 1 = none, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. For each patient, laboratory data on plasma calcium corrected for albumin, phosphorus and parathyroid hormone (PTH) levels were retrieved every 6 months up to 5 years prior to the CT scan. Individual mean values over 5 years were calculated. RESULTS: We included 31 patients: 12 patients with peritoneal calcifications and 19 patients without. No difference was found in aortic calcification scores (median scores: 3 versus 3). Also, median (range) calcium, 10.7 (9.6-11.5) versus 10.3 (9.4-11.3) mg/dL; phosphorus, 5.2 (3.4-7.0) versus 4.9 (2.9-6.5) mg/dL; and PTH levels, 271 (101-910) versus 263 (40-1197) pg/mL were not different between patients with and without peritoneal calcifications. CONCLUSIONS: The presence of peritoneal calcifications in long-term PD patients could not be related to the presence of aortic calcifications or disturbances in mineral metabolism. Perhaps, local peritoneal factors play a role in the formation of peritoneal calcifications. PMID- 20591815 TI - Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. AB - BACKGROUND: Aminoglycosides (AG) cause acute kidney injury (AKI), but the incidence and severity distribution are unclear, particularly in non-critically ill children. We determined the incidence, severity and risk factors of AG associated AKI and assessed for associations with longer hospitalization and higher costs. METHODS: At Texas Children's Hospital, we conducted a retrospective cohort study of children treated with AG for >= 5 days in 2005, excluding children with admission primary renal diagnoses. AKI was defined by the paediatric Risk, Injury, Failure, Loss, End Stage Kidney Disease (pRIFLE) and Acute Kidney Injury Network (AKIN) definitions. Multiple logistic and linear regression analyses were used to assess independence of associations with outcomes. RESULTS: Five hundred and fifty-seven children [mean +/- SD age = 8.0 +/- 5.9 years, 286 (51%) male, 489 (88%) gentamicin] were studied. The AKI rate was 33% and 20% by pRIFLE and AKIN definitions, respectively. Longer treatment, higher baseline estimated glomerular filtration rate, being on a medicine (versus surgical) treatment service and prior AG treatment were independent risk factors for AKI development. AKI by pRIFLE or AKIN was independently associated with longer hospital stay and higher total hospital costs. The pRIFLE definition was more sensitive for AKI detection, but the AKIN definition was more strongly related to outcomes. CONCLUSIONS: AKI is common and associated with poorer outcomes in non-critically ill children treated with AG. Future research should attempt to understand how to best define AKI in the non-critical illness paediatric setting. PMID- 20591816 TI - Skin autofluorescence is associated with renal function and cardiovascular diseases in pre-dialysis chronic kidney disease patients. AB - BACKGROUND: Tissue accumulation of advanced glycation end-products (AGE) is thought to be a contributing factor to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has shown associations with CVD in haemodialysis patients. The present study aimed to evaluate relationships of skin autofluorescence to renal function as well as CVD in pre-dialysis patients with chronic kidney disease (CKD). METHODS: Subjects in this cross sectional analysis comprised 304 pre-dialysis CKD patients [median age, 62.0 years; median estimated glomerular filtration rate (eGFR), 54.3 mL/min/1.73 m(2); diabetes, n = 81 (26.6%)]. AGE accumulation in skin was assessed by skin autofluorescence using an autofluorescence reader. Relationships between skin autofluorescence, eGFR, CVD history and other parameters were evaluated. RESULTS: Skin autofluorescence correlated negatively with eGFR (r = -0.42, P < 0.01) and increased as CKD stage advanced. Multiple regression analysis revealed significant correlations of skin autofluorescence with age, presence of diabetes, eGFR and CVD history in CKD patients (R(2) = 30%). Age, male gender, smoking history, skin autofluorescence and eGFR were significantly correlated with CVD history, and multiple logistic regression analysis identified age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.03-1.15; P < 0.01], history of smoking (OR, 6.50; 95%CI, 1.94-21.83; P < 0.01) and skin autofluorescence (OR, 3.74; 95%CI, 1.54-9.24; P < 0.01) as independent factors. CONCLUSIONS: Tissue AGE accumulation measured as skin autofluorescence increased as GFR decreased and was related to CVD history in CKD patients. Non-invasive autofluorescence readers may provide potential markers for clinical risk assessment in pre-dialysis CKD patients. PMID- 20591817 TI - Dependence of beam broadening on detection angle in scanning transmission electron microtomography. AB - It has been shown that scanning transmission electron microtomography (STEMT) is quite effective for observing specimens with thicknesses on the order of micrometers in three dimensions (3D). In STEMT, the specimen is scanned using a focused electron beam, and the electrons from the convergence point are detected at the detector placed at a certain detection angle. Until recently, a wide detection angle corresponding to the mode often called the dark-field (DF) mode was mainly used. Although the detection angle can vary and is one of the crucial experimental factors in STEMT, its effect on 3D reconstruction has never been discussed from either an experimental or a theoretical viewpoint. Moreover, the effectiveness of another mode of electron tomography, transmission electron microtomography (TEMT), is not clear. In the present study, a polymeric specimen, an acrylonitrile butadiene styrene resin, with a thickness of ~1 mum and a fixed volume was observed using three different modes, namely, TEMT, small detection angle STEMT referred to as bright-field STEMT, and DF-STEMT, in order to examine their advantages and disadvantages by observing multiple scattering of electrons inside the specimen. PMID- 20591818 TI - Prevalence and associations of partner abuse in women attending Russian general practice. AB - BACKGROUND: although a solid body of international general practice studies focuses on epidemiological issues of partner abuse against women, there is no research in Russian primary care targeting its cultural diversity to provide sufficient evidence for health care intervention towards this important public health issue. OBJECTIVES: to measure lifetime and 1-year prevalence of partner abuse among women attending Russian general practice, to test for associations between lifetime partner abuse and socio-demographic factors and to assess the acceptability to women of GPs asking about partner abuse. METHODS: cross sectional self-administered questionnaire survey in 24 general practices in St Petersburg. Russian Composite Abuse Scale was administered to consecutive woman patients. Prevalence was reported as proportions and logistic regression was used to test associations. RESULTS: one thousand two hundred and thirty-two respondents (age range 16-70 years); 70% response. Lifetime prevalence of partner abuse was 37.1% [95% confidence interval (CI) = 34.4-40.0%] and 1-year prevalence was 7.2% (95% CI = 4.6-11.2%). The multivariate analysis showed that cohabiting women were 1.9 (95% CI = 1.3-2.8) times more likely and divorced women were 2.3 (95% CI = 1.1-4.8) times more likely to be abused than married respondents. Only 34.7% (95% CI = 31.5-38.0%) of women would agree to GPs asking about partner abuse. CONCLUSIONS: the high prevalence of partner abuse is consistent with international findings in general practice-based studies. The predominantly negative attitude of women towards being asked about abuse is a challenge to future domestic violence interventions in Russian practices. PMID- 20591819 TI - Authentic professional competence in clinical neuropsychology. AB - Authentic Professional Competence in Clinical Neuropsychology was Dr Denney's 2009 presidential address at the Annual Conference of the National Academy of Neuropsychology. In his address, he highlighted the need for clinical neuropsychologists to strive for authentic professional competence rather than a mere pretense of expertise. Undisputed credibility arises from authentic professional competence. Achieving authentic professional competence includes the completion of a thorough course of training within the defined specialty area and validation of expertise by one's peers through the board certification process. Included in the address were survey results regarding what the consumer believes about board certification as well as survey results regarding the experiences of recent neuropsychology diplomates. It is important for neuropsychologists to realize that the board certification process enhances public perception and credibility of the field as well as personal growth for the neuropsychologist. Lastly, he urged all neuropsychologists to support the unified training model and pursue board certification. PMID- 20591820 TI - Updating progress in sarcoma therapy with mTOR inhibitors. AB - BACKGROUND: Sarcomas are a diverse group of difficult-to-treat connective tissue neoplasms. The mammalian target of rapamycin (mTOR) pathway has been identified as a therapeutic target in many sarcomas and this article reviews the role of this pathway and updates clinical data for the available mTOR inhibitors. DESIGN: Reference sources were selected by the author for searches in PubMed and EMBASE, with search terms dependent on the particular subtopic. RESULTS: mTOR is a protein kinase that regulates cell growth and proliferation and is abnormally activated in many human tumours. Several disruptions of phosphatidylinositol-3' kinase (PI3K)-Akt signalling are associated with different sarcoma types. The macrolide antibiotic rapamycin and synthetic derivatives sirolimus, temsirolimus, everolimus and ridaforolimus have been investigated in several tumour types and their potential for the treatment of sarcoma is being explored, with varying degrees of success. The PI3K-Akt-mTOR pathway is also implicated in resistance mechanisms to antineoplastic therapies, and mTOR inhibitors therefore have the potential to restore sensitivity to patients with treatment-resistant disease. CONCLUSIONS: The PI3K-Akt-mTOR pathway is an exciting target for therapy in many types of solid malignancies and its blockade represents an opportunity to improve outcomes in poor-prognosis sarcoma. PMID- 20591821 TI - Improving early breast cancer detection: focus on methylation. AB - The need for additional breast cancer screening tools is indisputably high, as one may conclude from the high rate of interval malignancies in women undergoing regular screening. DNA promoter methylation frequently occurs during breast carcinogenesis and is an early event in this process. Moreover, a field defect for methylation has been described and methylation values can reliably be assessed in limited amounts of DNA. Simultaneous detection of methylation of a panel of genes in breast fluids and/or blood derivatives could be both sufficiently specific and sensitive to be of additive value to current imaging based screening methods. This review describes the recent developments in methylation detection in breast fluids, serum and plasma that paved the way for large prospective studies. These studies will provide us with the definite answer as to what will be the additive value of defining the methylation status of specific genes to current imaging-based screening methods. PMID- 20591822 TI - Class-specific restrictions define primase interactions with DNA template and replicative helicase. AB - Bacterial primase is stimulated by replicative helicase to produce RNA primers that are essential for DNA replication. To identify mechanisms regulating primase activity, we characterized primase initiation specificity and interactions with the replicative helicase for gram-positive Firmicutes (Staphylococcus, Bacillus and Geobacillus) and gram-negative Proteobacteria (Escherichia, Yersinia and Pseudomonas). Contributions of the primase zinc-binding domain, RNA polymerase domain and helicase-binding domain on de novo primer synthesis were determined using mutated, truncated, chimeric and wild-type primases. Key residues in the beta4 strand of the primase zinc-binding domain defined class-associated trinucleotide recognition and substitution of these amino acids transferred specificity across classes. A change in template recognition provided functional evidence for interaction in trans between the zinc-binding domain and RNA polymerase domain of two separate primases. Helicase binding to the primase C terminal helicase-binding domain modulated RNA primer length in a species specific manner and productive interactions paralleled genetic relatedness. Results demonstrated that primase template specificity is conserved within a bacterial class, whereas the primase-helicase interaction has co-evolved within each species. PMID- 20591823 TI - A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing. AB - Huntington disease (HD) is a neurodegenerative disorder that predominantly affects neurons of the forebrain. We have applied the Illumina massively parallel sequencing to deeply analyze the small RNA populations of two different forebrain areas, the frontal cortex (FC) and the striatum (ST) of healthy individuals and individuals with HD. More than 80% of the small-RNAs were annotated as microRNAs (miRNAs) in all samples. Deep sequencing revealed length and sequence heterogeneity (IsomiRs) for the vast majority of miRNAs. Around 80-90% of the miRNAs presented modifications in the 3'-terminus mainly in the form of trimming and/or as nucleotide addition variants, while the 5'-terminus of the miRNAs was specially protected from changes. Expression profiling showed strong miRNA and isomiR expression deregulation in HD, most being common to both FC and ST. The analysis of the upstream regulatory regions in co-regulated miRNAs suggests a role for RE1-Silencing Transcription Factor (REST) and P53 in miRNAs downregulation in HD. The putative targets of deregulated miRNAs and seed-region IsomiRs strongly suggest that their altered expression contributes to the aberrant gene expression in HD. Our results show that miRNA variability is a ubiquitous phenomenon in the adult human brain, which may influence gene expression in physiological and pathological conditions. PMID- 20591824 TI - MicroRNA-181a modulates gene expression of zinc finger family members by directly targeting their coding regions. AB - MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that specifically bind to the 3' untranslated region (3'UTR) of target genes in animals. However, some recent studies have demonstrated that miRNAs also target the coding regions of mammalian genes. Here, we show that miRNA-181a downregulates the expression of a large number of zinc finger genes (ZNFs). Bioinformatics analysis revealed that these ZNFs contain many miR-181a seed-matched sites within their coding sequences (CDS). In particular, miR-181a 8-mer-matched sequences were mostly localized to the regions coding for the ZNF C2H2 domain. A series of reporter assays confirmed that miR-181a inhibits the expression of ZNFs by directly targeting their CDS. These inhibitory effects might be due to the multiple target sites located within the ZNF genes. In conclusion, our findings indicate that some miRNA species may regulate gene family by targeting their coding regions, thus providing an important and novel perspective for decoding the complex mechanism of miRNA/mRNA interplay. PMID- 20591825 TI - Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms. AB - Wilms' tumour suppressor gene, WT1, is mutated/deleted in approximately 15% of Wilms' tumours, highly expressed in the majority of other cancers and is essential for normal embryonic development. The gene encodes multiple isoforms of a zinc-finger (ZF) protein with diverse cellular functions, in particular participating in both transcriptional and post-transcriptional gene regulation. Physical interactions of other cellular proteins with WT1 are known to modulate its function. However, despite the isolation of several WT1-binding proteins, the mechanisms involved in regulating WT1 activities are not clearly understood. In this study, we report the identification of the Kruppel-like ZF protein, ZNF224, as a novel human WT1-associating protein and demonstrate that ZNF224 and its isoform ZNF255 show a specific pattern of interaction with the WT1 splicing variants WT1(-KTS) and WT1(+KTS). These interactions occur in different subcellular compartments and are devoted to control different cellular pathways. The nuclear interaction between ZNF224 and WT1(-KTS) results in an increase in trascriptional activation mediated by WT1, implying that ZNF224 acts as a co regulator of WT1, whereas, on the contrary, the results obtained for ZNF255 suggest a role for this protein in RNA processing together with WT1. Moreover, our data give the first functional information about the involvement of ZNF255 in a specific molecular pathway, RNA maturation and processing. PMID- 20591826 TI - Attenuation of MCP-1/CCL2 expression ameliorates neuropathy in a mouse model for Charcot-Marie-Tooth 1X. AB - The chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) has been previously shown to be an important mediator of macrophage-related neural damage in models of two distinct inherited neuropathies, Charcot-Marie-Tooth (CMT) 1A and 1B. In mice deficient in the gap junction protein connexin 32 (Cx32def), an established model for the X-chromosome-linked dominant form of CMT (CMT1X), we investigated the role of the chemokine in macrophage immigration and neural damage by crossbreeding the Cx32def mice with MCP-1 knockout mutants. In Cx32def mutants typically expressing increased levels of MCP-1, macrophage numbers were strongly elevated, caused by an MCP-1-mediated influx of haematogenous macrophages. Curiously, the complete genetic deletion of MCP-1 did not cause reduced macrophage numbers in the nerves due to compensatory proliferation of resident macrophages. In contrast, and as already seen in other CMT models, heterozygous deletion of MCP-1 led to reduced numbers of phagocytosing macrophages and an alleviation of demyelination. Whereas alleviated demyelination was transient, axonal damage was persistently improved and even robust axonal sprouting was detectable at 12 months. Other axon-related features were alleviated electrophysiological parameters, reduced muscle denervation and atrophy, and increased muscle strength. Similar to models for CMT1A and CMT1B, we identified MEK-ERK signalling as mediating MCP-1 expression in Cx32-deficient Schwann cells. Blocking this pathway by the inhibitor CI-1040 caused reduced MCP-1 expression, attenuation of macrophage increase and amelioration of myelin- and axon-related alterations. Thus, attenuation of MCP-1 upregulation by inhibiting ERK phosphorylation might be a promising approach to treat CMT1X and other so far untreatable inherited peripheral neuropathies in humans. PMID- 20591828 TI - Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: implications for tumor metastasis. AB - Galectin-3 is a glycan-binding protein that mediates cell-cell and/or cell extracellular matrix (ECM) interactions. Although galectin-3 is implicated in the progression of various types of cancers, the mechanisms by which galectin-3 enhances metastasis remain unclear. In order to elucidate the role of galectin-3 in the complex multistage process of cancer metastasis, we examined galectin-3 and galectin-3-binding site expression in a series of 82 spontaneous canine mammary tumors (CMT) and two CMT cell lines. Benign CMT tumors exhibited strong nuclear/cytoplasmic galectin-3 immunostaining, whereas malignant CMT tumors and metastases exhibited dramatically decreased galectin-3 expression with the majority of the immunostaining confined to the cytoplasm. Interestingly, intravascular tumor cells overexpressed galectin-3 regardless of their location. CMT-U27 xenografts displayed the same pattern of galectin-3 expression found in spontaneous malignant CMT. In parallel with the downregulation of galectin-3, malignant CMT displayed an overall loss of galectin-3-binding sites in the ECM and focal expression of galectin-3-binding sites mainly detected in intravascular tumor cells and endothelium. Furthermore, loss of galectin-3-binding sites was correlated with the downregulation of GLT25D1, a beta (1-O) galactosyltransferase that modifies collagen, and upregulation of stromal galectin-1. Finally, GLT25D1 mRNA expression was strikingly downregulated in malignant CMT-U27 compared with the benign cell line, and its expression was further decreased in a galectin-3 knockdown CMT-U27 cell line. We therefore hypothesized that the loss of galectin 3-binding sites in the ECM in conjunction with the overexpression of galectin-3 in specific tumor cell subpopulations are crucial events for the development of mammary tumor metastases. PMID- 20591827 TI - CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis. AB - De novo mutation of the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7) is the primary cause of CHARGE syndrome, a complex developmental disorder characterized by the co-occurrence of a specific set of birth defects. Recent studies indicate that CHD7 functions as a transcriptional regulator in the nucleoplasm. Here, we report based on immunofluorescence and western blotting of subcellular fractions that CHD7 is also constitutively localized to the nucleolus, the site of rRNA transcription. Standard chromatin immunoprecipitation (ChIP) assays indicate that CHD7 physically associates with rDNA, a result that is also observable upon alignment of whole-genome CHD7 ChIP coupled with massively parallel DNA sequencing data to the rDNA reference sequence. ChIP-chop analyses demonstrate that CHD7 specifically associates with hypomethylated, active rDNA, suggesting a role as a positive regulator of rRNA synthesis. Consistent with this hypothesis, siRNA-mediated depletion of CHD7 results in hypermethylation of the rDNA promoter and a concomitant reduction of 45S pre-rRNA levels. Accordingly, cells overexpressing CHD7 show increased levels of 45S pre rRNA compared with control cells. Depletion of CHD7 also reduced cell proliferation and protein synthesis. Lastly, compared with wild-type ES cells, the levels of 45S pre-rRNA are reduced in both Chd7(+/-) and Chd7(-/-) mouse ES cells, as well as in Chd7(-/-) whole mouse embryos and multiple tissues dissected from Chd7(+/-) embryos. Together with previously published studies, these results indicate that CHD7 dually functions as a regulator of both nucleoplasmic and nucleolar genes and provide a novel avenue for investigation into the pathogenesis of CHARGE syndrome. PMID- 20591829 TI - Functional analysis of the C-terminal domain of the WbaP protein that mediates initiation of O antigen synthesis in Salmonella enterica. AB - WbaP catalyzes the transfer of galactose-1-phosphate onto undecaprenyl phosphate (Und-P). The enzyme belongs to a large family of bacterial membrane proteins required for initiation of the synthesis of O antigen lipopolysaccharide and polysaccharide capsules. Previous work in our laboratory demonstrated that the last transmembrane helix and C-terminal tail region of WbaP (WbaP(CT)) are sufficient for enzymatic activity. Here, we demonstrate the cytoplasmic location of the WbaP C-terminal tail and show that WbaP(CT) domain N-terminally fused to thioredoxin (TrxA-WbaP(CT)) exhibits improved protein folding and enhanced transferase activity. Alanine replacement of highly conserved charged or polar amino acids identified seven critical residues for enzyme activity in vivo and in vitro. Four of these residues are located in regions predicted to be alpha helical. These regions and their secondary structure predictions are conserved in distinct WbaP family members, suggesting they may contribute to form a conserved catalytic center. PMID- 20591830 TI - Gingival capillary changes and oral motor weakness in juvenile dermatomyositis. AB - OBJECTIVE: We assessed the orofacial involvement in JDM, and evaluated the possible association of gingival and mandibular mobility alterations with demographic data, periodontal indices, clinical features, muscle enzyme levels, JDM scores and treatment. METHODS: Twenty-six JDM patients were studied and compared with 22 healthy controls. Orofacial evaluation included clinical features, dental and periodontal assessment, mandibular function and salivary flow. RESULTS: The mean current age was similar in patients with JDM and controls (P > 0.05). A unique gingival alteration characterized by erythema, capillary dilation and bush-loop formation was observed only in JDM patients (61 vs 0%, P = 0.0001). The frequencies of altered mandibular mobility and reduced mouth opening were significantly higher in patients with JDM vs controls (50 vs 14%, P = 0.013; 31 vs 0%, P = 0.005). Comparison of the patients with and without gingival alteration showed that the former had lower values of median of cementoenamel junction (-0.26 vs -0.06 mm, P = 0.013) and higher gingival bleeding index (27.7 vs 14%, P = 0.046). This pattern of gingival alteration was not associated with periodontal disease [plaque index (P =0.332) and dental attachment loss (P = 0.482)]. The medians for skin DAS and current dose of MTX were higher in JDM with gingival alteration (2.5 vs 0.5, P = 0.029; 28.7 vs 15, P = 0.012). A significant association of lower median manual muscle testing with a reduced ability to open the mouth was observed in patients with JDM than those without this alteration (79 vs 80, P = 0.002). CONCLUSIONS: The unique gingival pattern associated with cutaneous disease activity, distinct from periodontal disease, suggests that gingiva is a possible target tissue for JDM. In addition, muscle weakness may be a relevant factor for mandibular mobility. PMID- 20591832 TI - Efficacy of rituximab in a patient with lupus nephritis despite low levels of CD19. PMID- 20591831 TI - Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand. AB - OBJECTIVE: Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of the present study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with idiopathic inflammatory myopathies (IIMs) and healthy individuals. METHODS: A protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 24 circulating cytokines, including B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) of patients with IIMs and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional interrelationships among these pathological cytokines. RESULTS: Univariate analysis demonstrated that a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with IIMs relative to unaffected controls including IL-10, IL-13, IFN-alpha, epidermal growth factor (EGF), VEGF, fibroblast growth factor (FGF), CCL3 [macrophage inflammatory protein (MIP-1alpha)], CCL4 (MIP-1beta) and CCL11 (eotaxin), whereas G-CSF was significantly reduced in IIM patients. Correlational clustering was able to discriminate between, and hence sub-classify patients with IIMs. DFA identified EGF, IFN-alpha, VEGF, CCL3 (MIP-1alpha) and IL-12p40, as analytes with the strongest discriminatory power among various myositis patients and controls. CONCLUSIONS: Our findings suggest that these factors modulate myositis pathology and help to identify differences between subsets of the disease. PMID- 20591833 TI - Acupuncture for rheumatic conditions: an overview of systematic reviews. AB - OBJECTIVE: Several systematic reviews (SRs) have assessed the effectiveness of acupuncture for rheumatic conditions, often with contradictory conclusions. Our aim is to provide a critical evaluation and summary of these data. METHODS: Electronic searches were conducted in 15 databases to locate all SRs on acupuncture for rheumatic conditions published since 2000. Data were extracted by the authors according to pre-defined criteria. RESULTS: We found 30 SRs that met our inclusion criteria. They related to the following rheumatic conditions: FM, low back pain, lateral elbow pain, musculoskeletal pain, orthopaedic diseases, OA, RA, shoulder pain, frozen shoulder, neck disorder, AS and sciatica. Their conclusions were in several instances contradictory. Relatively clear evidence emerged to suggest that acupuncture is effective for OA, low back pain and lateral elbow pain and ineffective for FM and RA. CONCLUSION: Many SRs have recently been done. Only for OA, low back pain and lateral elbow pain is the evidence sufficiently sound to warrant positive recommendations of this therapy in routine care of rheumatic patients. PMID- 20591835 TI - Retrotransposition and genomic imprinting. AB - Studies of large imprinted clusters, such as the Gnas locus, have revealed much about the significance of DNA methylation, transcription and other factors in the establishment and maintenance of imprinted gene expression. However, the complexity of such loci can make manipulating them and interpreting the results challenging. We review here a distinct class of imprinted genes, which have arisen by retrotransposition, and which have the potential to be used as models for the dissection of the fundamental features and mechanisms required for imprinting. They are also of interest in their own right, generating diversity in the transcriptome and providing raw material upon which selection can act. PMID- 20591836 TI - Genome-wide identification of new imprinted genes. AB - In the mid-1980s, elegant studies on mouse embryos revealed that both parental genomes are required for normal development leading to the discovery of genomic imprinting. Imprinting is a parent-of-origin-dependent epigenetic mechanism whereby a subset of autosomal genes is expressed from only one of the parental alleles. Imprinting control involves both DNA- and histone-methylation, which differentially mark the parental alleles. More than a hundred imprinted genes have been identified so far, many of which play important roles in the regulation of growth and development. Nonetheless, the full extent of imprinting and its biological functions remain underestimated. In this review, we describe recently developed strategies to identify novel imprinted genes and highlight the potential of combining several high throughput approaches. By integrating databases obtained from epigenome- and transcriptome-wide analyses, we now have the unique opportunity to identify all the imprinted genes in the human/mouse genomes. PMID- 20591834 TI - Vaccinations in patients with immune-mediated inflammatory diseases. AB - Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals. PMID- 20591837 TI - New insight in ethylene signaling: autokinase activity of ETR1 modulates the interaction of receptors and EIN2. AB - Ethylene insensitive 2 (EIN2), an integral membrane protein of the ER network, has been identified as the central regulator of the ethylene signaling pathway. Still, the mechanism by which the ethylene signal is transferred from the receptors to EIN2 has not been solved yet. Here, we show that protein phosphorylation is a key mechanism to control the interaction of EIN2 and the receptors. In vivo and in vitro fluorescence studies reveal that the kinase domain of the receptors is essential for the interaction. Cyanide, an ethylene agonist, which is known to reduce auto-phosphorylation of the ethylene receptor ethylene resistant 1 (ETR1) or a mutation in the kinase domain of ETR1 that prevents auto-phosphorylation (H353A), increases the affinity of the receptors for EIN2. On the other hand, mimicking permanent auto-phosphorylation of ETR1 as in the mutant H353E releases the EIN2-ETR1 interaction from the control by the plant hormone. Based on our data, we propose a novel model on the integration of EIN2 in the ethylene signaling cascade. PMID- 20591838 TI - The isogene 1-deoxy-D-xylulose 5-phosphate synthase 2 controls isoprenoid profiles, precursor pathway allocation, and density of tomato trichomes. AB - Plant isoprenoids are formed from precursors synthesized by the mevalonate (MVA) pathway in the cytosol or by the methyl-D-erythritol 4-phosphate (MEP) pathway in plastids. Although some exchange of precursors occurs, cytosolic sesquiterpenes are assumed to derive mainly from MVA, while plastidial monoterpenes are produced preferentially from MEP precursors. Additional complexity arises in the first step of the MEP pathway, which is typically catalyzed by two divergent 1-deoxy-D xylulose 5-phosphate synthase isoforms (DXS1, DXS2). In tomato (Solanum lycopersicum), the SlDXS1 gene is ubiquitously expressed with highest levels during fruit ripening, whereas SlDXS2 transcripts are abundant in only few tissues, including young leaves, petals, and isolated trichomes. Specific down regulation of SlDXS2 expression was performed by RNA interference in transgenic plants to investigate feedback mechanisms. SlDXS2 down-regulation led to a decrease in the monoterpene beta-phellandrene and an increase in two sesquiterpenes in trichomes. Moreover, incorporation of MVA-derived precursors into residual monoterpenes and into sesquiterpenes was elevated as determined by comparison of 13C to 12C natural isotope ratios. A compensatory up-regulation of SlDXS1 was not observed. Down-regulated lines also exhibited increased trichome density and showed less damage by leaf-feeding Spodoptera littoralis caterpillars. The results reveal novel, non-redundant roles of DXS2 in modulating isoprenoid metabolism and a pronounced plasticity in isoprenoid precursor allocation. PMID- 20591839 TI - How are they really doing? Observation of inclusionary classroom participation for children with mild-to-moderate deafness. AB - Direct observation was utilized to study how 5 children with mild-to-moderate deafness participated within inclusive classroom settings. Responses to practice and prompt opportunities, levels of prompting required to follow classroom directions, and engagement were analyzed across students with mild-to-moderate deafness and were compared to students with normal hearing. Similar responses to practice and prompt opportunities were observed across students, and engagement data indicated that 4 children with mild-to-moderate deafness had similar rates to their peers. However, children with mild-to-moderate deafness required higher levels of prompting and were less accurate at following classwide verbal prompts. Agreement data on variables ranged between 83% and 99%, with the exception of 2 prompting levels. Social validity judgments indicated that the information was useful and important. Potential uses for data include consultation with teachers regarding interventions to increase student engagement and research regarding inclusionary practices. PMID- 20591840 TI - An analysis of the reading strategies used by adult and student deaf readers. AB - The purpose of this study was to identify and examine effective reading strategies used by adult deaf readers compared with student deaf readers. There were a total of 11 participants: 5 deaf adults ranging from 27 to 36 years and 6 deaf students ranging from 16 to 20 years. Assessment methods included interview and think-aloud procedures in which individuals were interrupted 3 times during the reading of a text to answer questions about their internal cognitive processes. It was found that both student and adult groups had highly skilled readers who demonstrated higher level reading strategies and less skilled readers who demonstrated lower level strategies, and only the highest skilled reader demonstrated both breadth and depth of strategies in all three categories: "constructing meaning," "monitoring and improving comprehension," and "evaluating comprehension." The study contributes evidence toward two identified gaps in the existing body of research: (a) the lack of investigation into the reading strategies utilized by deaf readers in text comprehension and (b) the overemphasis of most research on studying less skilled deaf readers while overlooking highly proficient deaf readers. PMID- 20591841 TI - Contributions of remote monitoring to the follow-up of implantable cardioverter defibrillator leads under advisory. AB - AIMS: Automatic daily transmission of data from implantable cardioverter defibrillators (ICDs) enables the remote monitoring of device status and leads function. We report on a 2-year experience with remote monitoring in 40 recipients of high-voltage ICD leads, prone to fracture and under advisory since October 2007. METHODS AND RESULTS: The ICDs were remotely monitored as well as systematically interrogated in the ambulatory department every 3 months. The patients were also seen in case of abnormal lead impedance, or other manifestations consistent with lead dysfunction. Over a mean follow-up of 22 +/- 4 months after ICD implantation, four lead dysfunctions were suspected because of remotely transmitted oversensing of noise artifacts, abrupt rise in pacing impedance, or both. A lead fracture needing lead replacement was confirmed in three patients (7.5%), two of them before any inappropriate therapy and one after the delivery of three inappropriate shocks. No lead failure was observed in the remaining 36 patients, either at the time of ambulatory visits or during remote monitoring. CONCLUSION: Remote monitoring allowed the early and reliable detection of ICD leads failure without requiring any patient intervention. PMID- 20591842 TI - Impact of red blood cell transfusion on platelet activation and aggregation in healthy volunteers: results of the TRANSFUSION study. AB - AIMS: The underlying mechanisms leading to recurrent ischaemic events or mortality after red blood cell (RBC) transfusion in anaemic acute coronary syndrome patients are poorly understood. The aim of this paper is to determine whether RBC transfusion increases platelet activation and aggregation. METHODS AND RESULTS: In vitro transfusions (n = 45) were performed by the addition of RBCs obtained from transfusion packs to fresh whole blood provided by healthy volunteers. Residual platelet aggregation (RPA) and maximal platelet aggregation (MPA) were assessed before and after in vitro transfusion using light transmission aggregometry performed with four different agonists. Flow cytometry was used for the measurement of P-selectin expression and vasodilatator stimulated phosphoprotein (VASP) platelet reactivity index (PRI). To control for the effect of haemoconcentration, the same experiments were repeated after hematocrit adjustment using volunteer's platelet poor plasma. Transfusion increased platelet aggregation as measured by RPA with ADP 5 uM (57.7 +/- 25 vs. 65.7 +/- 24%; P = 0.03) or Collagen 2 ug/mL (59.4 +/- 28 vs. 69.7 +/- 24%; P = 0.03). There were no significant differences with Arachidonic Acid 1.25 mM or Epinephrine 20 uM and results were similar when MPA was considered. Platelet activation was also increased by transfusion as confirmed by an elevation of P selectin expression induced by 20 uM ADP (12.2 +/- 18 vs. 23.9 +/- 18%; P = 0.002) or 50 uM ADP (15.4 +/- 18.6 vs.26.8 +/- 21.2%; P = 0.004) and an increase in VASP PRI (77.8 +/- 6 vs. 81.9 +/- 3%; P = 0.03). These effects were all independent of hematocrit. CONCLUSION: Red blood cell transfusion increases platelet activation and aggregation in vitro in healthy volunteers. This effect might be mediated through the P2Y(12) activation pathway. PMID- 20591843 TI - Identification of local- and habitat-dependent selection: scanning functionally important genes in nine-spined sticklebacks (Pungitius pungitius). AB - Understanding the selective forces promoting adaptive population divergence is a central issue in evolutionary biology. The role of environmental salinity in driving adaptation and evolution in aquatic organisms is still poorly understood. We investigated the relative impacts of habitat type (cf. saltwater vs. freshwater) and geographic area in shaping adaptive population divergence, as well as genes responsible for adaptation to different salinities in nine-spined sticklebacks (Pungitius pungitius). To this end, we employed a hitchhiking mapping approach with 111 microsatellite loci and one insertion/deletion locus including 63 loci situated within or close to genes with important physiological functions such as osmoregulation, growth, and thermal response. Using three pairs of marine and freshwater populations from different geographic areas, we identified several loci showing consistent evidence of being under directional selection in different outlier tests. Analyses of molecular variance at the loci under selection indicated that geographic area rather than habitat type has been acting as a central force in shaping adaptive population divergence. Nevertheless, both outlier tests and a spatial analysis method indicated that two loci (growth hormone receptor 2 and DEAD box polypeptide 56) are involved in adaptation to different habitats, implying that environmental salinity has been affecting them as a selective force. These loci are promising candidates for further investigations focusing on the molecular mechanisms of adaptation to marine and freshwater environments. PMID- 20591844 TI - Different phylogenomic approaches to resolve the evolutionary relationships among model fish species. AB - Comparative genomics holds the promise to magnify the information obtained from individual genome sequencing projects, revealing common features conserved across genomes and identifying lineage-specific characteristics. To implement such a comparative approach, a robust phylogenetic framework is required to accurately reconstruct evolution at the genome level. Among vertebrate taxa, teleosts represent the second best characterized group, with high-quality draft genome sequences for five model species (Danio rerio, Gasterosteus aculeatus, Oryzias latipes, Takifugu rubripes, and Tetraodon nigroviridis), and several others are in the finishing lane. However, the relationships among the acanthomorph teleost model fishes remain an unresolved taxonomic issue. Here, a genomic region spanning over 1.2 million base pairs was sequenced in the teleost fish Dicentrarchus labrax. Together with genomic data available for the above fish models, the new sequence was used to identify unique orthologous genomic regions shared across all target taxa. Different strategies were applied to produce robust multiple gene and genomic alignments spanning from 11,802 to 186,474 amino acid/nucleotide positions. Ten data sets were analyzed according to Bayesian inference, maximum likelihood, maximum parsimony, and neighbor joining methods. Extensive analyses were performed to explore the influence of several factors (e.g., alignment methodology, substitution model, data set partitions, and long branch attraction) on the tree topology. Although a general consensus was observed for a closer relationship between G. aculeatus (Gasterosteidae) and Di. labrax (Moronidae) with the atherinomorph O. latipes (Beloniformes) sister taxon of this clade, with the tetraodontiform group Ta. rubripes and Te. nigroviridis (Tetraodontiformes) representing a more distantly related taxon among acanthomorph model fish species, conflicting results were obtained between data sets and methods, especially with respect to the choice of alignment methodology applied to noncoding parts of the genomic region under study. This may limit the use of intergenic/noncoding sequences in phylogenomics until more robust alignment algorithms are developed. PMID- 20591845 TI - Mammalian evolution may not be strictly bifurcating. AB - The massive amount of genomic sequence data that is now available for analyzing evolutionary relationships among 31 placental mammals reduces the stochastic error in phylogenetic analyses to virtually zero. One would expect that this would make it possible to finally resolve controversial branches in the placental mammalian tree. We analyzed a 2,863,797 nucleotide-long alignment (3,364 genes) from 31 placental mammals for reconstructing their evolution. Most placental mammalian relationships were resolved, and a consensus of their evolution is emerging. However, certain branches remain difficult or virtually impossible to resolve. These branches are characterized by short divergence times in the order of 1-4 million years. Computer simulations based on parameters from the real data show that as little as about 12,500 amino acid sites could be sufficient to confidently resolve short branches as old as about 90 million years ago (Ma). Thus, the amount of sequence data should no longer be a limiting factor in resolving the relationships among placental mammals. The timing of the early radiation of placental mammals coincides with a period of climate warming some 100-80 Ma and with continental fragmentation. These global processes may have triggered the rapid diversification of placental mammals. However, the rapid radiations of certain mammalian groups complicate phylogenetic analyses, possibly due to incomplete lineage sorting and introgression. These speciation-related processes led to a mosaic genome and conflicting phylogenetic signals. Split network methods are ideal for visualizing these problematic branches and can therefore depict data conflict and possibly the true evolutionary history better than strictly bifurcating trees. Given the timing of tectonics, of placental mammalian divergences, and the fossil record, a Laurasian rather than Gondwanan origin of placental mammals seems the most parsimonious explanation. PMID- 20591846 TI - Bioactive ceramic-reinforced composites for bone augmentation. AB - Biomaterials have been used to repair the human body for millennia, but it is only since the 1970s that man-made composites have been used. Hydroxyapatite (HA) reinforced polyethylene (PE) is the first of the 'second-generation' biomaterials that have been developed to be bioactive rather than bioinert. The mechanical properties have been characterized using quasi-static, fatigue, creep and fracture toughness testing, and these studies have allowed optimization of the production method. The in vitro and in vivo biological properties have been investigated with a range of filler content and have shown that the presence of sufficient bioactive filler leads to a bioactive composite. Finally, the material has been applied clinically, initially in the orbital floor and later in the middle ear. From this initial combination of HA in PE other bioactive ceramic polymer composites have been developed. PMID- 20591847 TI - Diversity, competition, extinction: the ecophysics of language change. AB - As indicated early by Charles Darwin, languages behave and change very much like living species. They display high diversity, differentiate in space and time, emerge and disappear. A large body of literature has explored the role of information exchanges and communicative constraints in groups of agents under selective scenarios. These models have been very helpful in providing a rationale on how complex forms of communication emerge under evolutionary pressures. However, other patterns of large-scale organization can be described using mathematical methods ignoring communicative traits. These approaches consider shorter time scales and have been developed by exploiting both theoretical ecology and statistical physics methods. The models are reviewed here and include extinction, invasion, origination, spatial organization, coexistence and diversity as key concepts and are very simple in their defining rules. Such simplicity is used in order to catch the most fundamental laws of organization and those universal ingredients responsible for qualitative traits. The similarities between observed and predicted patterns indicate that an ecological theory of language is emerging, supporting (on a quantitative basis) its ecological nature, although key differences are also present. Here, we critically review some recent advances and outline their implications and limitations as well as highlight problems for future research. PMID- 20591848 TI - A comparative analysis of synthetic genetic oscillators. AB - Synthetic biology is a rapidly expanding discipline at the interface between engineering and biology. Much research in this area has focused on gene regulatory networks that function as biological switches and oscillators. Here we review the state of the art in the design and construction of oscillators, comparing the features of each of the main networks published to date, the models used for in silico design and validation and, where available, relevant experimental data. Trends are apparent in the ways that network topology constrains oscillator characteristics and dynamics. Also, noise and time delay within the network can both have constructive and destructive roles in generating oscillations, and stochastic coherence is commonplace. This review can be used to inform future work to design and implement new types of synthetic oscillators or to incorporate existing oscillators into new designs. PMID- 20591850 TI - Trophallaxis and prophylaxis: social immunity in the carpenter ant Camponotus pennsylvanicus. AB - In social insects, group behaviour can increase disease resistance among nest mates and generate social prophylaxis. Stomodeal trophallaxis, or mutual feeding through regurgitation, may boost colony-level immunocompetence. We provide evidence for increased trophallactic behaviour among immunized workers of the carpenter ant Camponotus pennsylvanicus, which, together with increased antimicrobial activity of the regurgitate droplet, help explain the improved survival of droplet recipient ants relative to controls following an immune challenge. We have identified a protein related to cathepsin D, a lysosomal protease, as a potential contributor to the antimicrobial activity. The combined behavioural and immunological responses to infection in these ants probably represent an effective mechanism underlying the social facilitation of disease resistance, which could potentially produce socially mediated colony-wide prophylaxis. The externalization and sharing of an individual's immune responses via trophallaxis could be an important component of social immunity, allowing insect colonies to thrive under high pathogenic pressures. PMID- 20591849 TI - Titanium oral implants: surface characteristics, interface biology and clinical outcome. AB - Bone-anchored titanium implants have revolutionized oral healthcare. Surface properties of oral titanium implants play decisive roles for molecular interactions, cellular response and bone regeneration. Nevertheless, the role of specific surface properties, such as chemical and phase composition and nanoscale features, for the biological in vivo performance remains to be established. Partly, this is due to limited transfer of state-of-the-art preparation techniques to complex three-dimensional geometries, analytical tools and access to minute, intact interfacial layers. As judged by the available results of a few randomized clinical trials, there is no evidence that any particular type of oral implant has superior long-term success. Important insights into the recruitment of mesenchymal stem cells, cell-cell communication at the interface and high resolution imaging of the interface between the surface oxide and the biological host are prerequisites for the understanding of the mechanisms of osseointegration. Strategies for development of the next generation of material surface modifications for compromised tissue are likely to include time and functionally programmed properties, pharmacological modulation and incorporation of cellular components. PMID- 20591851 TI - Earlier pupping in harbour seals, Phoca vitulina. AB - The annual reproductive cycle of most seal species is characterized by a tight synchrony of births. Typically, timing of birth shows little inter-annual variation. Here, however we show that harbour seals Phoca vitulina from the Wadden Sea (southeast North Sea) have shortened their yearly cycle, moving parturition to earlier dates since the early 1970s. Between 1974 and 2009, the birth date of harbour seals shifted on average by -0.71 d yr-1, three and a half weeks (25 days) earlier, in the Dutch part of the Wadden Sea. Pup counts available for other parts of the Wadden Sea were analysed, showing a similar shift. To elucidate potential mechanism(s) for this shift in pupping phenology, possible changes in population demography, changes in maternal life-history traits and variations in environmental conditions were examined. It was deduced that the most likely mechanism was a shortening of embryonic diapause. We hypothesize that this could have been facilitated by an improved forage base, e.g. increase of small fishes, attributable to overfishing of large predator fishes and size-selective fisheries. PMID- 20591852 TI - Correlated evolution of brain regions involved in producing and processing facial expressions in anthropoid primates. AB - Anthropoid primates are distinguished from other mammals by having relatively large primary visual cortices (V1) and complex facial expressions. We present a comparative test of the hypothesis that facial expression processing coevolved with the expansion of V1 in anthropoids. Previously published data were analysed using phylogenetic comparative methods. The results of our study suggest a pattern of correlated evolution linking social group size, facial motor control and cortical visual processing in catarrhines, but not platyrrhines. Catarrhines that live in relatively large social groups tended to have relatively large facial motor nuclei, and relatively large primary visual cortices. We conclude that catarrhine brains are adapted for producing and processing complex facial displays. PMID- 20591853 TI - The world's smallest whale population? AB - The North Pacific right whale (Eubalaena japonica) was heavily exploited by both nineteenth century whaling and recent (1960s) illegal Soviet catches. Today, the species remains extremely rare especially in the eastern North Pacific. Here, we use photographic and genotype data to calculate the first mark-recapture estimates of abundance for right whales in the Bering Sea and Aleutian Islands. The estimates were very similar: photographic = 31 (95% CL 23-54), genotyping = 28 (95% CL 24-42). We also estimated the population contains eight females (95% CL 7-18) and 20 males (95% CL 17-37). Although these estimates may relate to a Bering Sea subpopulation, other data suggest that the total eastern North Pacific population is unlikely to be much larger. Its precarious status today-the world's smallest whale population for which an abundance estimate exists-is a direct consequence of uncontrolled and illegal whaling, and highlights the past failure of international management to prevent such abuses. PMID- 20591854 TI - Insulin receptor substrate influences female caste development in honeybees. AB - The insulin/insulin-like signalling (IIS) network is conserved among animals and is central to growth and development. In eusocial honeybees (Apis mellifera), IIS is hypothesized to shape female caste fate. We tested this hypothesis via RNA interference (RNAi) knockdown of the insulin receptor substrate (IRS) homologue, a key adaptor protein in IIS. Female larvae naturally develop into queens (reproductives) or workers (helpers) after being fed rich versus limited diets, respectively. Feeding larvae a rich diet mixed with dsRNA (double stranded RNA) targeting irs gene transcript decreased irs mRNA abundance and caused development of worker morphology. Controls receiving rich larval diet and control dsRNA developed queen morphology. Whole-body mass spectrometry profiling of larvae collected 72, 96 and 120 h after dsRNA treatments revealed proteomic differences between irs gene knockdowns and controls, including levels of hexamerin 110, a storage protein connected to natural caste differences. PMID- 20591855 TI - The May threshold and life-history allometry. AB - One of Robert May's classic results was finding that population dynamics become chaotic when the average lifetime rate of reproduction exceeds a certain value. Populations whose reproductive rates exceed this May threshold probably become extinct. The May threshold in each case depends upon the shape of the density dependence curve, which differs among models of population growth. However, species of different sizes and generation times that share a roughly similar density-dependence curve will also share a similar May threshold. Here, we argue that this fact predicts a striking allometric regularity among animal taxa: lifetime reproductive rate should be roughly independent of body size. Such independence has been observed in diverse taxa, but has usually been ascribed to a fortuitous combination of physiologically based life-history allometries. We suggest, instead, that the ecological elimination of unstable populations within groups that share a value of the May threshold is a likely cause of this allometry. PMID- 20591856 TI - Simulating sauropod manus-only trackway formation using finite-element analysis. AB - The occurrence of sauropod manus-only trackways in the fossil record is poorly understood, limiting their potential for understanding locomotor mechanics and behaviour. To elucidate possible causative mechanisms for these traces, finite element analyses were conducted to model the indentation of substrate by the feet of Diplodocus and Brachiosaurus. Loading was accomplished by applying mass, centre of mass and foot surface area predictions to a range of substrates to model track formation. Experimental results show that when pressure differs between manus and pes, as determined by the distribution of weight and size of respective autopodia, there is a range of substrate shear strengths for which only the manus (or pes) produce enough pressure to deform the substrate, generating a track. If existing reconstructions of sauropod feet and mass distributions are correct, then different taxa will produce either manus- or pes only trackways in specific substrates. As a result of this work, it is predicted that the occurrence of manus- or pes-only trackways may show geo-temporal correlation with the occurrence of body fossils of specific taxa. PMID- 20591857 TI - Systematic review of the prevalence of suicide in veterinary surgeons. AB - BACKGROUND: An accumulating body of research demonstrates that risk of suicide varies between occupational groups. Identification of the occupations at risk, and the factors that contribute to the increased risk of suicide in these groups is essential for the development of effective suicide prevention strategies. There is preliminary evidence to suggest that veterinary surgeons are a group at risk. AIMS: To conduct a systematic review of studies of rates and methods of suicide in the veterinary profession. METHODS: A systematic search of the international research literature was performed in May 2008. The data from the 19 studies of the prevalence of suicide in the veterinary profession were extracted by two independent reviewers and analysed. RESULTS: Between 0 and 43% of veterinary surgeon deaths were due to suicide. In all but one of the 15 studies presenting risk of suicide in veterinary surgeons with a comparison population, an elevated risk was found. The better quality studies with the lowest risk of bias indicated that in the UK, the rate of suicide in the veterinary profession was at least three times the general population rate. Studies of the methods of suicide veterinary surgeons use suggest that self-poisoning and firearms are particularly common. CONCLUSIONS: There appears to be an elevated risk of suicide for veterinary surgeons in several countries. Access to means of suicide influences the methods used and may contribute to increased risk. PMID- 20591859 TI - Effects of personality on territory defence in communication networks: a playback experiment with radio-tagged great tits. AB - Individuals often differ consistently in behaviour across time and contexts, and such consistent behavioural differences are commonly described as personality. Personality can play a central role in social behaviour both in dyadic interactions and in social networks. We investigated whether explorative behaviour, as proxy of personality of territorial male great tits (Parus major), predicts their own and their neighbours' territorial responses towards simulated intruders. Several weeks prior to playback, subjects were taken from the wild to test their exploratory behaviour in a standard context in the laboratory. Exploratory behaviour provides a proxy of personality along a slow-fast explorer continuum. Upon release, males were radio-tracked and subsequently exposed to interactive playback simulating a more or a less aggressive territorial intruder (by either overlapping or alternating broadcast songs with the subjects' songs). At the same time, we radio-tracked a neighbour of the playback subject. Male vocal responses during playback and spatial movements after playback varied according to male explorative behaviour and playback treatment. Males with lower exploration scores approached the loudspeaker less, and sang more songs, shorter songs and songs with slower element rates than did males with higher exploration scores. Moreover, neighbour responses were related to the explorative behaviour of the subject receiving the playback but not to their own explorative behaviour. Our overall findings reveal for the first time how personality traits affect resource defence within a communication network providing new insights on the cause of variation in resource defence behaviour. PMID- 20591858 TI - Measuring cognitive reserve based on the decomposition of episodic memory variance. AB - In later adulthood brain pathology becomes common and trajectories of cognitive change are heterogeneous. Among the multiple determinants of late-life cognitive course, cognitive reserve has been proposed as an important factor that modifies or buffers the impact of brain pathology on cognitive function. This article presents and investigates a novel method for measuring and investigating such factors. The core concept is that in a population where pathology is common and variably present, 'reserve' may be defined as the difference between the cognitive performance predicted by an individual's level of pathology and that individual's actual performance. By this definition, people whose measured cognitive performance is better than predicted by pathology have high reserve, whereas those who perform worse than predicted have low reserve. To test this hypothesis, we applied a latent variable model to data from a diverse ageing cohort and decomposed the variance in a measure of episodic memory into three components, one predicted by demographics, one predicted by pathology as measured by structural MRI and a 'residual' or 'reserve' term that included all remaining variance. To investigate the plausibility of this approach, we then tested the residual component as an operational measure of reserve. Specific predictions about the effects of this putative reserve measure were generated from a general conceptual model of reserve. Each was borne from the results. The results show that the current level of reserve, as measured by this decomposition approach, modifies rates of conversion from mild cognitive impairment to dementia, modifies rates of longitudinal decline in executive function and, most importantly, attenuates the effect of brain atrophy on cognitive decline such that atrophy is more strongly associated with cognitive decline in subjects with low reserve than in those with high reserve. Decomposing the variance in cognitive function scores offers a promising new approach to the measure and study of cognitive reserve. PMID- 20591860 TI - Parasite prevalence and the worldwide distribution of cognitive ability. AB - In this study, we hypothesize that the worldwide distribution of cognitive ability is determined in part by variation in the intensity of infectious diseases. From an energetics standpoint, a developing human will have difficulty building a brain and fighting off infectious diseases at the same time, as both are very metabolically costly tasks. Using three measures of average national intelligence quotient (IQ), we found that the zero-order correlation between average IQ and parasite stress ranges from r=-0.76 to r=-0.82 (p<0.0001). These correlations are robust worldwide, as well as within five of six world regions. Infectious disease remains the most powerful predictor of average national IQ when temperature, distance from Africa, gross domestic product per capita and several measures of education are controlled for. These findings suggest that the Flynn effect may be caused in part by the decrease in the intensity of infectious diseases as nations develop. PMID- 20591861 TI - Identification of an ant queen pheromone regulating worker sterility. AB - The selective forces that shape and maintain eusocial societies are an enduring puzzle in evolutionary biology. Ordinarily sterile workers can usually reproduce given the right conditions, so the factors regulating reproductive division of labour may provide insight into why eusociality has persisted over evolutionary time. Queen-produced pheromones that affect worker reproduction have been implicated in diverse taxa, including ants, termites, wasps and possibly mole rats, but to date have only been definitively identified in the honeybee. Using the black garden ant Lasius niger, we isolate the first sterility-regulating ant queen pheromone. The pheromone is a cuticular hydrocarbon that comprises the majority of the chemical profile of queens and their eggs, and also affects worker behaviour, by reducing aggression towards objects bearing the pheromone. We further show that the pheromone elicits a strong response in worker antennae and that its production by queens is selectively reduced following an immune challenge. These results suggest that the pheromone has a central role in colony organization and support the hypothesis that worker sterility represents altruistic self-restraint in response to an honest quality signal. PMID- 20591862 TI - Sensitive males: inbreeding depression in an endangered bird. AB - Attempts to conserve threatened species by establishing new populations via reintroduction are controversial. Theory predicts that genetic bottlenecks result in increased mating between relatives and inbreeding depression. However, few studies of wild sourced reintroductions have carefully examined these genetic consequences. Our study assesses inbreeding and inbreeding depression in a free living reintroduced population of an endangered New Zealand bird, the hihi (Notiomystis cincta). Using molecular sexing and marker-based inbreeding coefficients estimated from 19 autosomal microsatellite loci, we show that (i) inbreeding depresses offspring survival, (ii) male embryos are more inbred on average than female embryos, (iii) the effect of inbreeding depression is male biased and (iv) this population has a substantial genetic load. Male susceptibility to inbreeding during embryo and nestling development may be due to size dimorphism, resulting in faster growth rates and more stressful development for male embryos and nestlings compared with females. This work highlights the effects of inbreeding at early life-history stages and the repercussions for the long-term population viability of threatened species. PMID- 20591863 TI - Gene copy-number polymorphism in nature. AB - Differences between individuals in the copy-number of whole genes have been found in every multicellular species examined thus far. Such differences result in unique complements of protein-coding genes in all individuals, and have been shown to underlie adaptive phenotypic differences. Here, we review the evidence for copy-number variants (CNVs), focusing on the methods used to detect them and the molecular mechanisms responsible for generating this type of variation. Although there are multiple technical and computational challenges inherent to these experimental methods, next-generation sequencing technologies are making such experiments accessible in any system with a sequenced genome. We further discuss the connection between copy-number variation within species and copy number divergence between species, showing that these values are exactly what one would expect from similar comparisons of nucleotide polymorphism and divergence. We conclude by reviewing the growing body of evidence for natural selection on copy-number variants. While it appears that most genic CNVs--especially deletions are quickly eliminated by selection, there are now multiple studies demonstrating a strong link between copy-number differences at specific genes and phenotypic differences in adaptive traits. We argue that a complete understanding of the molecular basis for adaptive natural selection necessarily includes the study of copy-number variation. PMID- 20591864 TI - Limited CD4+ T cell proliferation leads to preservation of CD4+ T cell counts in SIV-infected sooty mangabeys. AB - Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections result in chronic virus replication and progressive depletion of CD4+ T cells, leading to immunodeficiency and death. In contrast, 'natural hosts' of SIV experience persistent infection with high virus replication but no severe CD4+ T cell depletion, and remain AIDS-free. One important difference between pathogenic and non-pathogenic infections is the level of activation and proliferation of CD4+ T cells. We analysed the relationship between CD4+ T cell number and proliferation in HIV, pathogenic SIV in macaques, and non-pathogenic SIV in sooty mangabeys (SMs) and mandrills. We found that CD4+ T cell proliferation was negatively correlated with CD4+ T cell number, suggesting that animals respond to the loss of CD4+ T cells by increasing the proliferation of remaining cells. However, the level of proliferation seen in pathogenic infections (SIV in rhesus macaques and HIV) was much greater than in non pathogenic infections (SMs and mandrills). We then used a modelling approach to understand how the host proliferative response to CD4+ T cell depletion may impact the outcome of infection. This modelling demonstrates that the rapid proliferation of CD4+ T cells in humans and macaques associated with low CD4+ T cell levels can act to 'fuel the fire' of infection by providing more proliferating cells for infection. Natural host species, on the other hand, have limited proliferation of CD4+ T cells at low CD4+ T cell levels, which allows them to restrict the number of proliferating cells susceptible to infection. PMID- 20591865 TI - Parallel adaptive evolution of Atlantic cod on both sides of the Atlantic Ocean in response to temperature. AB - Despite the enormous economic and ecological importance of marine organisms, the spatial scales of adaptation and biocomplexity remain largely unknown. Yet, the preservation of local stocks that possess adaptive diversity is critical to the long-term maintenance of productive stable fisheries and ecosystems. Here, we document genomic evidence of range-wide adaptive differentiation in a broadcast spawning marine fish, Atlantic cod (Gadus morhua), using a genome survey of single nucleotide polymorphisms. Of 1641 gene-associated polymorphisms examined, 70 (4.2%) tested positive for signatures of selection using a Bayesian approach. We identify a subset of these loci (n=40) for which allele frequencies show parallel temperature-associated clines (p<0.001, r2=0.89) in the eastern and western north Atlantic. Temperature associations were robust to the statistical removal of geographic distance or latitude effects, and contrasted 'neutral' loci, which displayed no temperature association. Allele frequencies at temperature-associated loci were significantly correlated, spanned three linkage groups and several were successfully annotated supporting the involvement of multiple independent genes. Our results are consistent with the evolution and/or selective sweep of multiple genes in response to ocean temperature, and support the possibility of a new conservation paradigm for non-model marine organisms based on genomic approaches to resolving functional and adaptive diversity. PMID- 20591866 TI - Hantavirus infections in fluctuating host populations: the role of maternal antibodies. AB - Infected females may transfer maternal antibodies (MatAbs) to their offspring, which may then be transiently protected against infections the mother has encountered. However, the role of maternal protection in infectious disease dynamics in wildlife has largely been neglected. Here, we investigate the effects of Puumala hantavirus (PUUV)-specific MatAbs on PUUV dynamics, using 7 years' data from a cyclic bank vole population in Finland. For the first time to our knowledge, we partition seropositivity data from a natural population into separate dynamic patterns for MatAbs and infection. The likelihood of young of the year carrying PUUV-specific MatAbs during the breeding season correlated positively with infection prevalence in the overwintered parent population in the preceding spring. The probability of PUUV infection varied between seasons (highest in spring, lowest in late summer) and depended on population structure, but was also, in late autumn, notably, negatively related to summer MatAb prevalence, as well as to infection prevalence earlier in the breeding season. Hence, our results suggest that high infection prevalence in the early breeding season leads to a high proportion of transiently immune young individuals, which causes delays in transmission. This suggests, in turn, that MatAb protection has the potential to affect infection dynamics in natural populations. PMID- 20591867 TI - Kin competition, natal dispersal and the moulding of senescence by natural selection. AB - Most theoretical models for the evolution of senescence have assumed a very large, well mixed population. Here, we investigate how limited dispersal and kin competition might influence the evolution of ageing by deriving indicators of the force of selection, similar to Hamilton (Hamilton 1966 J. Theor. Biol. 12, 12 45). Our analytical model describes how the strength of selection on survival and fecundity changes with age in a patchy population, where adults are territorial and a fraction of juveniles disperse between territories. Both parent-offspring competition and sib competition then affect selection on age-specific life history traits. Kin competition reduces the strength of selection on survival. Mutations increasing mortality in some age classes can even be favoured by selection, but only when fecundity deteriorates rapidly with age. Population structure arising from limited dispersal however selects for a broader distribution of reproduction over the lifetime, potentially slowing down reproductive senescence. The antagonistic effects of limited dispersal on age schedules of fecundity and mortality cast doubts on the generality of conditions allowing the evolution of 'suicide genes' that increase mortality rates without other direct pleiotropic effects. More generally, our model illustrates how limited dispersal and social interactions can indirectly produce patterns of antagonistic pleiotropy affecting vital rates at different ages. PMID- 20591868 TI - The evolution of menopause in cetaceans and humans: the role of demography. AB - Human females stop reproducing long before they die. Among other mammals, only pilot and killer whales exhibit a comparable period of post-reproductive life. The grandmother hypothesis suggests that kin selection can favour post reproductive survival when older females help their relatives to reproduce. But although there is an evidence that grandmothers can provide such assistance, it is puzzling why menopause should have evolved only among the great apes and toothed whales. We have previously suggested (Cant & Johnstone 2008 Proc. Natl Acad. Sci. USA 105, 5332-5336 (doi:10.1073/pnas.0711911105)) that relatedness asymmetries owing to female-biased dispersal in ancestral humans would have favoured younger females in reproductive competition with older females, predisposing our species to the evolution of menopause. But this argument appears inapplicable to menopausal cetaceans, which exhibit philopatry of both sexes combined with extra-group mating. Here, we derive general formulae for 'kinship dynamics', the age-related changes in local relatedness that occur in long-lived social organisms as a consequence of dispersal and mortality. We show that the very different social structures of great apes and menopausal whales both give rise to an increase in local relatedness with female age, favouring late-life helping. Our analysis can therefore help to explain why, of all long-lived, social mammals, it is specifically among the great apes and toothed whales that menopause and post-reproductive helping have evolved. PMID- 20591869 TI - Motion perception and visual signal design in Anolis lizards. AB - Anolis lizards communicate with displays consisting of motion of the head and body. Early portions of long-distance displays require movements that are effective at eliciting the attention of potential receivers. We studied signal motion efficacy using a two-dimensional visual-motion detection (2DMD) model consisting of a grid of correlation-type elementary motion detectors. This 2DMD model has been shown to accurately predict Anolis lizard behavioural response. We tested different patterns of artificially generated motion and found that an abrupt 0.3 degrees shift of position in less than 100 ms is optimal. We quantified motion in displays of 25 individuals from five species. Four species employ near-optimal movement patterns. We tested displays of these species using the 2DMD model on scenes with and without moderate wind. Display movements can easily be detected, even in the presence of windblown vegetation. The fifth species does not typically use the most effective display movements and display movements cannot be discerned by the 2DMD model in the presence of windblown vegetation. A number of Anolis species use abrupt up-and-down head movements approximately 10 mm in amplitude in displays, and these movements appear to be extremely effective for stimulating the receiver visual system. PMID- 20591870 TI - Character displacement in the fighting colours of Hetaerina damselflies. AB - Aggression between species is a seldom-considered but potentially widespread mechanism of character displacement in secondary sexual characters. Based on previous research showing that similarity in wing coloration directly influences interspecific territorial aggression in Hetaerina damselflies, we predicted that wing coloration would show a pattern of character displacement (divergence in sympatry). A geographical survey of four Hetaerina damselfly species in Mexico and Texas showed evidence for character displacement in both species pairs that regularly occurs sympatrically. Hetaerina titia, a species that typically has large black wing spots and small red wing spots, shifted to having even larger black spots and smaller red wing spots at sites where a congener with large red wing spots is numerically dominant (Hetaerina americana or Hetaerina occisa). Hetaerina americana showed the reverse pattern, shifting towards larger red wing spots where H. titia is numerically dominant. This pattern is consistent with the process of agonistic character displacement, but the ontogenetic basis of the shift remains to be demonstrated. PMID- 20591871 TI - Scaling of sensorimotor control in terrestrial mammals. AB - Sensorimotor control is greatly affected by two factors--the time it takes for an animal to sense and respond to stimuli (responsiveness), and the ability of an animal to distinguish between sensory stimuli and generate graded muscle forces (resolution). Here, we demonstrate that anatomical limitations force a necessary trade-off between responsiveness and resolution with increases in animal size. To determine whether responsiveness is prioritized over resolution, or resolution over responsiveness, we studied how size influences the physiological mechanisms underlying sensorimotor control. Using both new electrophysiological experiments and existing data, we determined the maximum axonal conduction velocity (CV) in animals ranging in size from shrews to elephants. Over the 100-fold increase in leg length, CV was nearly constant, increasing proportionally with mass to the 0.04 power. As a consequence, larger animals are burdened with relatively long physiological delays, which may have broad implications for their behaviour, ecology and evolution, including constraining agility and requiring prediction to help control movements. PMID- 20591872 TI - Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. AB - BACKGROUND: An efficient oocyte cryopreservation method is mandatory to establish a successful egg-banking programme. Although there are increasing reports showing good clinical outcomes after oocyte cryopreservation, there is still a lack of large controlled studies evaluating the effectiveness of oocyte cryo-banking. In this study, we aimed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. METHODS: A randomized, prospective, triple-blind, single-centre, parallel-group controlled-clinical trial (NCT00785993), including 600 recipients (alpha = 0.05 and power of 80% for sample-size calculation) selected among 1032 eligible patients from November 2008 to September 2009, was designed to compare the outcome of vitrified-banked oocytes with the gold standard procedure of employing fresh oocytes. The study was designed to establish the superiority of the ongoing pregnancy rate (OPR) of fresh oocytes over that of vitrified oocytes, by performing a likelihood ratio test in a logistic regression analysis expressed as odds ratio (OR) with 95% confidence interval (CI). A limit of 0.66 for OR of vitrified versus fresh groups was defined to set up a possible conversion from superiority to non-inferiority. Randomization was performed 1:1 based on a computer randomization list in vitrification (n = 300) or fresh groups (n = 300). The primary end-point was the OPR per randomized patient i.e. intention-to-treat population (ITT). Secondary end-points were clinical pregnancy (CPR), implantation (IR) and fertilization rates, respectively. Additionally, embryo developmental characteristics were recorded. RESULTS: There were no differences in donor ovarian stimulation parameters, demographic baseline characteristics for donors and recipients, ovum donation indications or male factor distribution between groups (NS). The OPR per ITT was 43.7 and 41.7% in the vitrification and fresh groups, respectively. The OR of OPR was 0.921 in favour of the vitrification group. Nevertheless, the 95% CI was 0.667-1.274, thus the superiority of fresh group with respect to OPR was not proven (P = 0.744). Non-inferiority of the vitrified group compared with the fresh group was shown with a margin of 0.667, which was above the pre-established non-inferiority limit of 0.66. CPR per cycle (50.2 versus 49.8%; P = 0.933) or per embryo-transfer (55.4 versus 55.6% ; P = 0.974), and IR (39.9 versus 40.9%; P = 0.745) were similar for patients receiving either vitrified or fresh oocytes. The proportion of top-quality embryos obtained either by inseminated oocyte (30.8 versus 30.8% for Day-2; and 36.1 versus 37.7% for Day-3, respectively) or by cleaved embryos (43.6 versus 43.8% for Day-2 and 58.4 versus 60.7% for Day-3, respectively) was similar between groups (NS). CONCLUSIONS: This controlled randomized, clinical trial confirmed the effectiveness of oocyte cryo-storage in an ovum donation programme, failing to demonstrate the superiority of using fresh oocytes with respect to the use of vitrified egg-banked ones in terms of OPR. Instead, the non-inferiority of vitrified oocytes was confirmed. These findings involve highly relevant issues that may open a new range of possibilities in ART. PMID- 20591873 TI - Editorial: Leishmania survival mechanisms: the role of host phosphatases. PMID- 20591874 TI - A "Toll" for Th17 cell expansion. PMID- 20591875 TI - Can biogerontologists and geriatricians unite to apply aging science to health care in the decade ahead? AB - Biogerontologists and academic geriatricians are both dedicated to promoting a healthier longevity for our society from their perspectives of scientific research on aging and education as part of clinical care for older persons. Yet at the present time, the prospects for translating research advances made by the biogerontologists to improve the outlook for health care provided by the geriatricians are limited by a "gulf" that exists between them, with little shared dialogue or scientific interchange. This article sets forth a basis for a union between both disciplines to prepare for the potential application of basic aging research to the provision of health care, with the aim ultimately to extend "health span" during our life span. PMID- 20591877 TI - The accuracy of deceleration time of diastolic coronary flow measured by transthoracic echocardiography in predicting long-term left ventricular infarct size and function after reperfused myocardial infarction. AB - AIMS: Assessment of microvascular function after reperfused acute myocardial infarction (AMI) provides important insights for myocardial reperfusion and facilitates prediction of long-term left ventricular (LV) function and clinical outcome. In this study, we examined microvascular integrity 48 h after successful primary percutaneous coronary intervention (PCI) and compared predictive accuracy of the intracoronary pressure-wire- and transthoracic Doppler echocardiography based parameters in the estimation of long-term LV infarct size and function. METHODS AND RESULTS: The study group consisted of 30 anterior AMI patients who were treated successfully with primary PCI. Two days after primary PCI, microvascular integrity was evaluated. Coronary flow reserve (CFR), collateral flow index (CFIp), coronary wedge pressure (CWP), and index of microvascular resistance (IMR) were determined using intracoronary pressure wire. Deceleration time of coronary diastolic flow (DDT) was measured using transthoracic echocardiography. At 6 months, coronary angiography, echocardiography, and infarct size measurement were performed. Area under the curve, sensitivity, and specificity of the indices of microvascular perfusion in the prediction of late term infarct size were as follows: IMR (0.68 +/- 0.15, 69%, 60%), CFR (0.67 +/- 0.10, 66%, 59%), CWP (0.69 +/- 0.12, 70%, 72%), CFIp (0.64 +/- 0.10, 65%, 78%), and DDT (0.68 +/- 0.16, 69%, 79%). All of the microvascular perfusion indices, which have been used in this study, had comparable sensitivity and specificity in the prediction of long-term ejection fraction. There were no significant differences between areas under the curve of microvascular perfusion indices in the prediction of long-term infarct size and ejection fraction. CONCLUSION: As a non-invasive parameter, DDT was found to be as accurate as the invasive parameters of microvascular function in estimating long-term infarct size and LV function. Thus, simply measuring DDT in the reperfused infarct-related artery might provide useful and reliable estimate for early risk stratification. PMID- 20591876 TI - Aging is not associated with bone marrow-resident progenitor cell depletion. AB - Changes in progenitor cell biology remain at the forefront of many theories of biologic aging, but there are limited studies evaluating this in humans. Aging has been associated with a progressive depletion of circulating progenitor cells, but age-related bone marrow-resident progenitor cell depletion has not been systematically determined in humans. Patients undergoing total hip replacement were consented, and bone marrow and peripheral progenitor cells were enumerated based on aldehyde dehydrogenase activity and CD34 and CD133 expression. Circulating progenitors demonstrated an age-dependent decline. In contrast, marrow-resident progenitor cell content demonstrated no age association with any progenitor cell subtype. In humans, aging is associated with depletion of circulating, but not marrow-resident, progenitors. This finding has impact on the mechanism(s) responsible for age-related changes in circulating stem cells and important implications for the use of autologous marrow for the treatment of age related diseases. PMID- 20591878 TI - Torsion of young hearts: a speckle tracking study of normal infants, children, and adolescents. AB - AIM: Our aim was to study the rotational mechanics of the heart in a special population including neonates, young children, and adolescents. We showed the effect of age on torsion and the different rotational variables. This study is the first that focuses on neonatal heart mechanics. METHODS AND RESULTS: We recruited 70 normal children between few hours and 18 years old. We excluded abnormal rhythm and function. Short-axis parasternal views were taken at the base of the heart and the apex. Using the speckle tracking technique, we analysed the rotation curves at apex and base and calculated the net twist and torsion of the left ventricle (LV). We also calculated the twist and untwist rates to get the correlation with age and body surface area (BSA). Rotational patterns during diastole also were studied. Deformational time delay between the base and the apex was looked up. Apical rotation and net twist increased with age significantly (r = 0.41 and 0.38, respectively, P = 0.001) but when normalized by LV length there was fixed torsion among age groups. Rotation velocity declined with ageing during systole and diastole for both base and apex (r = -0.58 and 0.62 for twist rate, -0.69 and -0.6 for untwist rate, respectively, P < 0.001). Concordant results were reported for BSA. Deformational delay was decreasing with age (r = -0.74 for systolic and -0.53 for diastolic, P < 0.001). CONCLUSION: Infants hearts tend to deform more and faster than other groups. While apical twist and net twist increase with age, torsion is fixed among age groups. In young hearts, torsion is the result of differential twist. PMID- 20591879 TI - Pattern recognition and gestalt psychology: the day Nusslein-Volhard shouted "Toll!". PMID- 20591880 TI - Leak and obstruction with mask ventilation during simulated neonatal resuscitation. AB - OBJECTIVES: To evaluate mask technique during simulated neonatal resuscitation and test the effectiveness of training in optimal mask handling. STUDY DESIGN: Seventy participants(consultants, registrars and nurses) from neonatal units were asked to administer positive pressure ventilation at a flow of 8 l/min and a frequency of 40-60/min to a modified leak free, term newborn manikin (lung compliance 0.5 ml/cm H(2)O) using a Neopuff T-piece device. Recordings were made (1) before training, (2) after training in mask handling and (3) 3 weeks later. Leak was calculated. Obstruction (tidal volume <60% of optimal tidal volume) and severe obstruction (<30% of optimal tidal volume) were calculated when leak was minimal. RESULTS: For the 70 participants, median (IQR) leak was 71% (32-95%) before training, 10% (5-37%) directly after training and 15% (4-33%) 3 weeks later (p<0.001). When leak was minimal, gas flow obstruction was observed before, directly after training and 3 weeks later in 46%, 42% and 37% of inflations, respectively. Severe obstruction did not occur. CONCLUSIONS: Mask ventilation during simulated neonatal resuscitation was often hampered by large leaks at the face mask. Moderate airway obstruction occurred frequently when effort was taken to minimise leak. Training in mask ventilation reduced mask leak but should also focus on preventing airway obstruction. PMID- 20591881 TI - Hereditary diffuse gastric cancer: lifesaving total gastrectomy for CDH1 mutation carriers. PMID- 20591883 TI - Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome. AB - BACKGROUND: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCepsilon1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. METHOD: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0-373). RESULTS: Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. CONCLUSION: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients. PMID- 20591882 TI - Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. AB - 25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended. PMID- 20591884 TI - Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. AB - BACKGROUND: Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. METHODS: Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. RESULTS: Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. CONCLUSION: Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered. PMID- 20591886 TI - Intentional and successful use of a marginal donor heart with surgically corrected interventricular communication. AB - We describe a case of heart transplantation (HTX) performed using a heart from a 20-year-old donor who underwent surgical closure of a ventricular septal defect during childhood. Our 26-year-old patient was successfully discharged to a rehabilitation centre on day 20 post-transplantation. To our knowledge, this is the first report of an HTX performed with a 'redo' donor heart with previous surgical correction of a congenital heart defect. The widespread use of HTX as a therapeutic option is currently limited by the increase in number of patients listed annually for this procedure. The concomitant lack of organ donors has led to the concept of 'marginal donor' to broaden the classic standard criteria of donor suitability, but these extended criteria do not consider the possibility of using hearts that have undergone surgical correction of simple congenital heart defects. There has been a considerable increase in the grown-up congenital heart disease population over the past 20 years. We discuss the feasibility of using these hearts for transplantation and consider the limitations and precautions of such practice. PMID- 20591885 TI - The revised Ghent nosology for the Marfan syndrome. AB - The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counselling. These Ghent criteria, comprising a set of major and minor manifestations in different body systems, have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, are not applicable in children or necessitate expensive and specialised investigations. The recognition of variable clinical expression and the recently extended differential diagnosis further confound accurate diagnostic decision making. Moreover, the diagnosis of MFS--whether or not established correctly--can be stigmatising, hamper career aspirations, restrict life insurance opportunities, and cause psychosocial burden. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are the cardinal clinical features. In the absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of either of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a new scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines. PMID- 20591887 TI - Primary pleomorphic liposarcoma of pericardium. AB - We report a case of a 42-year-old man, who presented with a three-weeks' history of dyspnea and chest oppression induced by light activity, who had a large mass in the pericardium. Computed tomography showed a non-homogeneous density lobulated mass in the pericardial sac. The tumor underwent completely resection and histopathological analysis revealed the tumor to be a pleomorphic liposarcoma, which was composed predominantly of epithelioid cells. The patient is still alive 18 months after the diagnosis was made. The rare incidence of the liposarcoma of the pericardium can easily lead to a misdiagnosis clinically, and the final diagnosis here was made histopathologically. PMID- 20591888 TI - Successful support and separation from veno-venous extracorporeal membrane oxygenation support in a three-month-old patient following bidirectional Glenn procedure. AB - While extracorporeal membrane oxygenation (ECMO) is a useful mechanism of providing support in pediatric patients with cardiopulmonary dysfunction following surgery for congenital heart disease, outcomes have varied dramatically between distinct cardiac diagnoses. Reported outcomes of ECMO support following a bidirectional Glenn procedure in patients with single ventricle physiology are uniformly poor due in part to physiological and anatomical challenges inherent to cannulation in this population. We describe a unique veno-venous cannulation that can be applied to this patient population and has allowed for successful decannulation in our practice. PMID- 20591889 TI - Autologous platelet-rich plasma: effect on sternal healing in the sheep model. AB - Postcardiotomy sternal wound complications remain challenging. We looked at the effects of plasma rich in growth factors (PRGF) as an agent on sternal bone healing. In 24 female sheep, a median sternotomy was surgically created. In 12 of them (group control) the sternum was closed with three figure-of-eight wires. In 12 (group PRGF) three clots of autologous PRGF were applied over the sternum after its closure in the same manner as the control group. All sheep were killed at the nine-week follow-up. The sternum and the surrounding soft tissue was removed and fixed in formaldehyde. Transversal sections of the bone were obtained, decalcified and stained with hematoxylin and eosin. In the control group, we found extensive cartilaginous areas. In the PRGF group, the presence of trabecular bone tissue was common, with formation of hematopoietic medullary tissue. The process of new bone formation was accelerated in the PRGF group at the nine-week follow-up. In contrast, in the control group, the presence of cartilaginous tissue was the most common finding. PMID- 20591890 TI - A prospective randomized study to evaluate the renal impact of surgical revascularization strategy in diabetic patients. AB - Acute kidney injury (AKI) is a major postoperative complication following cardiac surgery. Diabetes mellitus is a major cause of nephropathy and end-stage renal failure. We aimed to evaluate the occurrence of adverse renal outcomes, in diabetic patients, between on-pump (CPB) and off-pump (OPCAB) coronary artery bypass graft (CABG). Seventy-one diabetic patients (36 and 35 patients in the CPB and OPCAB groups, respectively) were enrolled in a prospective randomized study. Renal tubular and glomerular functions, were monitored preoperatively and over five consecutive days. There was no significant difference between the groups in terms of age, gender, New York Heart Association class, Canadian Cardiovascular Society functional classification of angina grade and number of CABG. Intensive care unit stay, duration of intubation, hospital stay and bleeding were significantly higher in the CPB group. No significant differences in plasmatic creatinine, urinary creatinine, creatinine clearance, proteinuria or osmolality were detected. A significant rise in urinary albumine excretion occurred in both groups peaking on the operative day; for the on-pump CABG group (10+/-5 vs. 48+/ 57; P=0.015) and for the OPCAB group (11+/-6 vs. 37+/-59; P=0.04). Values were less important in the OPCAB group and return to the baseline was faster than in the CPB group. OPCAB attenuates sub-clinical AKI, in diabetic patients. PMID- 20591891 TI - Intercostal-subcostal combined complete port-accessed video-assisted lobectomy. AB - Video-assisted lobectomy procedures include a broad spectrum of operative techniques that range from complete thoracoscopic surgery to minithoracotomy with a thoracoscope serving only as a light source. We describe a modified method for thoracoscopic approach for lobectomy with thoracic muscle sparing based on a combined complete port-accessed technique with a subcostal incision. We have successfully used this technique for lobectomies in stage I lung tumors. Intercostal muscles and nerve injury preservation allied to fast track rehabilitation perioperative care allowed rapid postoperative recovery. PMID- 20591892 TI - Characteristic endobronchial ultrasound image of hemangiopericytoma/solitary fibrous tumor. AB - Hemangiopericytomatous pattern is characteristic of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) and certain histological features might indicate a malignant potential, but the behavior of HPC/SFT is unpredictable. Endobronchial ultrasound (EBUS) is a useful diagnostic device in that the ultrasonographic image can be viewed and the EBUS-transbronchial needle aspiration can obtain a biopsied sample. We herein report a patient undergoing multiple surgical resections of recurrent HPC/SFT. A 74-year-old man had undergone right upper lobectomy for HPC/SFT 15 years ago. He received a partial resection of the left lung and a resection of the anterior mediastinal mass for its recurrences 13 years and six years ago, respectively. He had also undergone surgery for gastric carcinoma two years ago. He then presented with a tumor measuring 3 x 4 cm in the subcarinal area. Preoperative EBUS revealed a tumor with abundant thin-walled vessel-like structures, which was consistent with HPC/SFT. The tumor was completely resected and was finally diagnosed as low-grade malignant HPC/SFT. PMID- 20591893 TI - Endobronchial inflammatory polyp as a rare complication of endobronchial ultrasound-transbronchial needle aspiration. AB - Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) offers a minimally invasive option for staging the mediastinum in suspected lung cancer but also in the diagnosis of mediastinal lesions accessible from the airways. EBUS-TBNA has been widely used for the evaluation of mediastinal and hilar lesions for several reasons, such as its minimally invasive nature, high diagnostic accuracy, needle aspiration under real-time visualization and excellent safety profile. Several recent studies have demonstrated that EBUS-TBNA have diagnostic accuracy equivalent to mediastinoscopy and in fact higher for certain lymph node stations. The present case report presents endobronchial inflammatory polyp as a complication after EBUS-TBNA in patients with tuberculous lymphadenitis and discusses the possible etiology of this complication, as well as implications for further application of this technology in patients with tuberculous lymphadenitis. PMID- 20591894 TI - Modified Nuss repair for pectus carinatum. AB - A minimally-invasive modified Nuss technique is described for pectus carinatum which has reduced risk of cardiac perforation compared to a standard Nuss procedure, and avoids performing the Ravitch procedure. PMID- 20591895 TI - Successful reversal of delayed paraplegia associated with chronic type A aortic dissection using a spinal drain. AB - Delayed neurological deficit (DND) following thoracic and thoracoabdominal aortic aneurysm repair refers to any neurological deficit in a patient who is evaluated to be neurologically intact postoperatively, but develops neurological problems several hours or days later which can be reversed if identified and treated immediately. We report a rare case where cerebrospinal fluid drainage reversed DND that happened 18 months following type A dissection repair. PMID- 20591896 TI - Root water potential integrates discrete soil physical properties to influence ABA signalling during partial rootzone drying. AB - To investigate the influence of different growing substrates (two mineral, two organic) on root xylem ABA concentration ([ABA](root)) and the contribution of the drying root system to total sap flow during partial rootzone drying (PRD), sunflower (Helianthus annuus L.) shoots were grafted onto the root systems of two plants grown in separate pots. Sap flow through each hypocotyl was measured below the graft union when one pot ('wet') was watered and other ('dry') was not. Each substrate gave unique relationships between dry pot matric potential (Psi(soil)), volumetric water content ((v)) or penetrometer resistance (Q) and either the fraction of photoperiod sap flow from roots in drying soil or [ABA](root). However, decreased relative sap flow, and increased [ABA](root), from roots in drying soil varied with root water potential (Psi(root)) more similarly across a range of substrates. The gradient between Psi(soil) and Psi(root) was greater in substrates with high sand or peat proportions, which may have contributed to a more sensitive response of [ABA](root) to Psi(soil) in these substrates. Whole plant transpiration was most closely correlated with the mean Psi(soil) of both pots, and then with detached leaf xylem ABA concentration. Although Psi(root) best predicted decreased relative sap flow, and increased [ABA](root), from roots in drying soil across a range of substrates, the inaccessibility of this variable in field studies requires a better understanding of how measurable soil variables (Psi(soil), (v), Q) affect Psi(root). PMID- 20591897 TI - Nitrogen to phosphorus ratio of plant biomass versus soil solution in a tropical pioneer tree, Ficus insipida. AB - It is commonly assumed that the nitrogen to phosphorus (N:P) ratio of a terrestrial plant reflects the relative availability of N and P in the soil in which the plant grows. Here, this was assessed for a tropical pioneer tree, Ficus insipida. Seedlings were grown in sand and irrigated with nutrient solutions containing N:P ratios ranging from <1 to >100. The experimental design further allowed investigation of physiological responses to N and P availability. Homeostatic control over N:P ratios was stronger in leaves than in stems or roots, suggesting that N:P ratios of stems and roots are more sensitive indicators of the relative availability of N and P at a site than N:P ratios of leaves. The leaf N:P ratio at which the largest plant dry mass and highest photosynthetic rates were achieved was approximately 11, whereas the corresponding whole-plant N:P ratio was approximately 6. Plant P concentration varied as a function of transpiration rate at constant nutrient solution P concentration, possibly due to transpiration-induced variation in the mass flow of P to root surfaces. The transpiration rate varied in response to nutrient solution N concentration, but not to nutrient solution P concentration, demonstrating nutritional control over transpiration by N but not P. Water-use efficiency varied as a function of N availability, but not as a function of P availability. PMID- 20591898 TI - Nicotinate/nicotinamide mononucleotide adenyltransferase-mediated regulation of NAD biosynthesis protects guard cells from reactive oxygen species in ABA mediated stomatal movement in Arabidopsis. AB - Nicotinamide adenine dinucleotide (NAD) and its derivative nicotinamide adenine dinucleotide phosphate (NADP) are indispensable co-factors in broad-spectrum metabolic events for the maintenance of cellular homeostasis in all living organisms. In this study, the cellular expression levels of NAD biosynthesis genes in Arabidopsis were investigated. A very high expression of nicotinate/nicotinamide mononucleotide adenyltransferase (NMNAT) was observed in the differentiated stomatal guard cells of the leaf surface. Transcriptional analysis confirmed that several genes in the biosynthesis pathway were also highly expressed in stomatal guard cells. In fact, NAD and NADP metabolisms were investigated during stomatal movement. Importantly, the generation of phytohormone ABA-induced reactive oxygen species, which acts as a signal for stomatal closure, was accompanied by markedly decreased levels of NAD. The ABA induced oxidative stress caused stomatal cell death in the nmnat mutant. Furthermore, stomata partially lost their ability to close leading to drought susceptibility. The stomata were less responsive to opening cues as well. These results indicate that NAD biosynthesis is involved in protecting guard cells from ABA-induced local oxidative stress via the regulation of NMNAT activity. In this study, it is demonstrated that NMNAT is essential for the maintenance of NAD homeostasis enabling sustainable stomatal movement. PMID- 20591899 TI - Role of photosynthesis and analysis of key enzymes involved in primary metabolism throughout the lifespan of the tobacco flower. AB - Although the physiological and economical relevance of flowers is recognized, their primary metabolism during development has not been characterized, especially combining protein, transcript, and activity levels of the different enzymes involved. In this work, the functional characterization of the photosynthetic apparatus, pigment profiles, and the main primary metabolic pathways were analysed in tobacco sepals and petals at different developmental stages. The results indicate that the corolla photosynthetic apparatus is functional and capable of fixing CO(2); with its photosynthetic activity mainly involved in pigment biosynthesis. The particular pattern of expression, across the tobacco flower lifespan, of several proteins involved in respiration and primary metabolism, indicate that petal carbon metabolism is highest at the anthesis stage; while some enzymes are activated at the later stages, along with senescence. The first signs of corolla senescence in attached flowers are observed after anthesis; however, molecular data suggest that senescence is already onset at this stage. Feeding experiments to detached flowers at anthesis indicate that sugars, but not photosynthetic activity of the corolla, are capable of delaying the senescence process. On the other hand, photosynthetic activity and CO(2) fixation is active in sepals, where high expression levels of particular enzymes were detected. Sepals remained green and did not show signs of senescence in all the flower developmental stages analysed. Overall, the data presented contribute to an understanding of the metabolic processes operating during tobacco flower development, and identify key enzymes involved in the different stages. PMID- 20591900 TI - Revealing diversity in structural and biochemical forms of C4 photosynthesis and a C3-C4 intermediate in genus Portulaca L. (Portulacaceae). AB - Portulacaceae is one of 19 families of terrestrial plants in which species having C(4) photosynthesis have been found. Representative species from major clades of the genus Portulaca were studied to characterize the forms of photosynthesis structurally and biochemically. The species P. amilis, P. grandiflora, P. molokiniensis, P. oleracea, P. pilosa, and P. umbraticola belong to the subgenus Portulaca and are C(4) plants based on leaf carbon isotope values, Kranz anatomy, and expression of key C(4) enzymes. Portulaca umbraticola, clade Umbraticola, is NADP-malic enzyme (NADP-ME)-type C(4) species, while P. oleracea and P. molokiniensis in clade Oleracea are NAD-ME-type C(4) species, all having different forms of Atriplicoid-type leaf anatomy. In clade Pilosa, P. amilis, P. grandiflora, and P. pilosa are NADP-ME-type C(4) species. They have Pilosoid-type anatomy in which Kranz tissues enclose peripheral vascular bundles with water storage in the centre of the leaf. Portulaca cf. bicolor, which belongs to subgenus Portulacella, is an NADP-ME C(4) species with Portulacelloid-type anatomy; it has well-developed Kranz chlorenchyma surrounding lateral veins distributed in one plane under the adaxial epidermis with water storage cells underneath. Portulaca cryptopetala (clade Oleracea), an endemic species from central South America, was identified as a C(3)-C(4) based on its intermediate CO(2) compensation point and selective localization of glycine decarboxylase of the photorespiratory pathway in mitochondria of bundle sheath cells. The C(4) Portulaca species which were examined also have cotyledons with Kranz-type anatomy, while the stems of all species have C(3)-type photosynthetic cells. The results indicate that multiple structural and biochemical forms of C(4) photosynthesis evolved in genus Portulaca. PMID- 20591901 TI - Engineering allosteric regulation into the hinge region of a circularly permuted TEM-1 beta-lactamase. AB - In nature, the activity of many enzymes involved in important biochemical pathways is controlled by binding a ligand in a site remote from the active site. The allosteric sites are frequently located in hinge regulatory subunits, in which a conformational change can occur and propagate to the active site. The enzymatic activity is then enhanced or decreased depending on the type of effectors. Many artificial binding sites have been created to engineer an allosteric regulation. Generally, these sites were engineered near the active site in loops or at the surface of contiguous helices or strands but rarely in hinge regions. This work aims at exploring the possibility of regulating a monomeric enzyme whose active site is located at the interface between two domains. We anticipated that binding of a ligand in the hinge region linking the domains would modify their positioning and, consequently, modulate the activity. Here, we describe the design of two mutants in a circularly permuted TEM-1 (cpTEM 1) beta-lactamase. The first one, cpTEM-1-His(3) was created by a rational design. It shows little regulation upon metal ion binding except for a weak activation with Zn(2+). The second one, cpTEM-1-3M-His(2), was selected by a directed evolution strategy. It is allosterically down-regulated by Zn(2+), Ni(2+) and Co(2+) with binding affinities around 300 microM. PMID- 20591902 TI - Analysis and prediction of VH/VL packing in antibodies. AB - The packing of V(H) and V(L) domains in antibodies can vary, influencing the topography of the antigen-combining site. However, until recently, this has largely been ignored in modelling antibody structure. We present an analysis of the degree of variability observed in known structures together with a machine learning approach to predict the packing angle. A neural network was trained on sets of interface residues and a genetic algorithm designed to perform 'feature selection' to define which sets of interface residues could be used most successfully to perform the prediction. While this training procedure was very computationally intensive, prediction is performed in a matter of seconds. Thus, not only do we provide a rapid method for predicting the packing angle, but also we define a set of residues that may be important in antibody humanization in order to obtain the correct binding site topography. PMID- 20591903 TI - MIReNA: finding microRNAs with high accuracy and no learning at genome scale and from deep sequencing data. AB - MOTIVATION: MicroRNAs (miRNAs) are a class of endogenes derived from a precursor (pre-miRNA) and involved in post-transcriptional regulation. Experimental identification of novel miRNAs is difficult because they are often transcribed under specific conditions and cell types. Several computational methods were developed to detect new miRNAs starting from known ones or from deep sequencing data, and to validate their pre-miRNAs. RESULTS: We present a genome-wide search algorithm, called MIReNA, that looks for miRNA sequences by exploring a multidimensional space defined by only five (physical and combinatorial) parameters characterizing acceptable pre-miRNAs. MIReNA validates pre-miRNAs with high sensitivity and specificity, and detects new miRNAs by homology from known miRNAs or from deep sequencing data. A performance comparison between MIReNA and four available predictive systems has been done. MIReNA approach is strikingly simple but it turns out to be powerful at least as much as more sophisticated algorithmic methods. MIReNA obtains better results than three known algorithms that validate pre-miRNAs. It demonstrates that machine-learning is not a necessary algorithmic approach for pre-miRNAs computational validation. In particular, machine learning algorithms can only confirm pre-miRNAs that look alike known ones, this being a limitation while exploring species with no known pre-miRNAs. The possibility to adapt the search to specific species, possibly characterized by specific properties of their miRNAs and pre-miRNAs, is a major feature of MIReNA. A parameter adjustment calibrates specificity and sensitivity in MIReNA, a key feature for predictive systems, which is not present in machine learning approaches. Comparison of MIReNA with miRDeep using deep sequencing data to predict miRNAs highlights a highly specific predictive power of MIReNA. AVAILABILITY: At the address http://www.ihes.fr/carbone/data8/. PMID- 20591904 TI - MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus. AB - MOTIVATION: We have implemented a coalescent simulation program for a structured population with selection at a single diploid locus. The program includes the functionality of the simulator ms to model population structure and demography, but adds a model for deme- and time-dependent selection using forward simulations. The program can be used, e.g. to study hard and soft selective sweeps in structured populations or the genetic footprint of local adaptation. The implementation is designed to be easily extendable and widely deployable. The interface and output format are compatible with ms. Performance is comparable even with selection included. AVAILABILITY: The program is freely available from http://www.mabs.at/ewing/msms/ along with manuals and examples. The source is freely available under a GPL type license. PMID- 20591905 TI - Integration of pathway knowledge into a reweighted recursive feature elimination approach for risk stratification of cancer patients. AB - MOTIVATION: One of the main goals of high-throughput gene-expression studies in cancer research is to identify prognostic gene signatures, which have the potential to predict the clinical outcome. It is common practice to investigate these questions using classification methods. However, standard methods merely rely on gene-expression data and assume the genes to be independent. Including pathway knowledge a priori into the classification process has recently been indicated as a promising way to increase classification accuracy as well as the interpretability and reproducibility of prognostic gene signatures. RESULTS: We propose a new method called Reweighted Recursive Feature Elimination. It is based on the hypothesis that a gene with a low fold-change should have an increased influence on the classifier if it is connected to differentially expressed genes. We used a modified version of Google's PageRank algorithm to alter the ranking criterion of the SVM-RFE algorithm. Evaluations of our method on an integrated breast cancer dataset comprising 788 samples showed an improvement of the area under the receiver operator characteristic curve as well as in the reproducibility and interpretability of selected genes. AVAILABILITY: The R code of the proposed algorithm is given in Supplementary Material. PMID- 20591906 TI - Biological knowledge bases using Wikis: combining the flexibility of Wikis with the structure of databases. AB - SUMMARY: In recent years, the number of knowledge bases developed using Wiki technology has exploded. Unfortunately, next to their numerous advantages, classical Wikis present a critical limitation: the invaluable knowledge they gather is represented as free text, which hinders their computational exploitation. This is in sharp contrast with the current practice for biological databases where the data is made available in a structured way. Here, we present WikiOpener an extension for the classical MediaWiki engine that augments Wiki pages by allowing on-the-fly querying and formatting resources external to the Wiki. Those resources may provide data extracted from databases or DAS tracks, or even results returned by local or remote bioinformatics analysis tools. This also implies that structured data can be edited via dedicated forms. Hence, this generic resource combines the structure of biological databases with the flexibility of collaborative Wikis. AVAILABILITY: The source code and its documentation are freely available on the MediaWiki website: http://www.mediawiki.org/wiki/Extension:WikiOpener. PMID- 20591907 TI - ABC-SysBio--approximate Bayesian computation in Python with GPU support. AB - MOTIVATION: The growing field of systems biology has driven demand for flexible tools to model and simulate biological systems. Two established problems in the modeling of biological processes are model selection and the estimation of associated parameters. A number of statistical approaches, both frequentist and Bayesian, have been proposed to answer these questions. RESULTS: Here we present a Python package, ABC-SysBio, that implements parameter inference and model selection for dynamical systems in an approximate Bayesian computation (ABC) framework. ABC-SysBio combines three algorithms: ABC rejection sampler, ABC SMC for parameter inference and ABC SMC for model selection. It is designed to work with models written in Systems Biology Markup Language (SBML). Deterministic and stochastic models can be analyzed in ABC-SysBio. AVAILABILITY: http://abc sysbio.sourceforge.net PMID- 20591908 TI - Is fascin really a useful marker in distinguishing between classical Hodgkin's lymphoma and various types of non-Hodgkin's lymphomas in difficult cases? AB - BACKGROUND: Fascin is an actin cross-linking protein, which is part of the cytoskeleton and involved in cell motility in several cell types. The differentiation of epithelial cells is greatly influenced by cell-matrix and cell cell interactions, which play an important role in the normal organisation and stabilisation of epithelial cells and maintain the cells in a non-migratory state. The malignant conversion of epithelial cells results from a phenotypic switch to a migratory state, which allows tumour invasion beyond the basement membrane, as well as metastasis. Such a switch requires complex rearrangements of the actin cytoskeleton and is governed by multiple actin-binding proteins including fascin. In non-neoplastic lymphoid tissue, fascin expression is highly selective and is predominantly localised in dendritic cells, while lymphocytes, plasma cells, etc are uniformly non-reactive. However, all or nearly all Reed Sternberg cells and their variants in all types of Hodgkin's lymphoma express fascin and are strongly immunoreactive for fascin. CONCLUSION: Lymphomas (Hodgkin's and non-Hodgkin's) are among the commonest malignancies seen in our practice. The Section of Histopathology at the Aga Khan University, Karachi is the largest centre for histopathology in Pakistan, a densely populated country with an estimated population of 170 million. The authors wanted to test the utility of Fascin in distinguishing between Hodgkin's lymphoma and morphologically closely related forms of non-Hodgkin's lymphoma such as diffuse large B cell non-Hodgkin's lymphoma and anaplastic large cell lymphoma in difficult cases. If found useful, this antibody could help us in reaching a correct diagnosis in difficult cases and allow appropriate patient management. PMID- 20591909 TI - Aberrant upregulation of MUC4 mucin expression in cutaneous condyloma acuminatum and squamous cell carcinoma suggests a potential role in the diagnosis and therapy of skin diseases. AB - AIM: Mucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications. METHODS: A total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7). RESULTS: While the normal epidermis showed a negative to weak positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative. CONCLUSION: The results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies. PMID- 20591910 TI - KRAS mutation and microsatellite instability in endometrial adenocarcinomas showing MELF-type myometrial invasion. AB - BACKGROUND: Some uterine endometrioid adenocarcinomas exhibit a distinctive morphological phenotype characterised by the formation of microcystic, elongated and fragmented (MELF) glands. Immunohistochemical studies have suggested that MELF-type changes represent an epithelial-mesenchymal transition which has been associated with KRAS activation in various tumours. AIMS: To investigate the molecular characteristics of endometrial tumours showing MELF, with particular reference to the frequencies of KRAS and BRAF mutations and of microsatellite instability (MSI). METHODS: MSI, and KRAS and BRAF mutation status, were assessed in 33 low-grade endometrial adenocarcinomas showing MELF features and the results compared with 33 control cases exhibiting a 'conventional' pattern of myometrial invasion. Standard histological parameters were also reviewed. RESULTS: Tumours with a MELF pattern of myometrial invasion showed more frequent vascular invasion and focal mucinous differentiation. KRAS mutations were more frequent in MELF positive than MELF negative tumours (45% vs 30%), but this difference was not statistically significant. BRAF mutations were not identified in any of the cases. MSI was identified in 20% of cases overall but did not correlate with the MELF phenotype. CONCLUSIONS: Mutations in KRAS and BRAF genes are not directly implicated in the development of a MELF pattern of invasion in endometrial carcinoma. However, RAS-associated signalling pathways could be activated through other genetic or epigenetic mechanisms. The characterisation of such alterations may become increasingly important as novel therapies are developed that target mediators involved in tumour invasion. PMID- 20591911 TI - Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue microarray-based study of 136 cases. AB - AIMS: Claudins are integral transmembrane proteins of the tight junctions, critical for maintaining cell adhesion and polarity. Alterations in the expression of individual claudins have been detected in carcinomas and appear to correlate with tumour progression. METHODS: In this study, a panel of anti claudin antibodies (anti-claudins 1, 2, 3, 4, 5 and 7) was employed to map claudin expression in 136 cases of oral squamous cell carcinoma (OSCC) organised in a tissue microarray. RESULTS: Claudins were expressed in a reticular pattern up to the prickle layer in normal mucosal epithelium. In OSCC, claudins were strongly present in well-differentiated tumours, they presented mild and low expression in moderately differentiated OSCC, and were negative in poorly differentiated OSCC; the absences of claudin 1 (p=0.002) and claudin 4 (p<0.001) were associated with moderately/poorly differentiated tumours. Strong expression of claudin 4 was associated with decreased perineural infiltration (p=0.024). Claudins 5 and 7 were mostly negative or weakly expressed in all cases studied. Expression of claudin 7 was associated with the early clinical stages of the disease, whereas loss of claudin 7 tended to be more frequent in advanced stages of OSCC (p=0.054). Absence of claudin 7 was also associated with absent vascular infiltration (p=0.045) and with presence of recurrence (p=0.052). CONCLUSIONS: Claudin expression patterns showed a strong correlation with histological type of OSCC; claudin expression was decreased in areas of invasion, and negative in poorly differentiated tumours. This pattern may be related to evolution and prognosis of these tumours, especially in the case of claudin 7, which seems to be associated with a poor prognosis in OSCC. PMID- 20591912 TI - Positive screening and carrier results for the England-wide universal newborn sickle cell screening programme by ethnicity and area for 2005-07. AB - AIMS: The overall aim of the new national newborn programme is to identify infants at risk of sickle cell disease to allow early detection and to minimise deaths and complications. METHODS: Universal screening for sickle cell disease was introduced in England between September 2003 and July 2006. The 13 newborn laboratories each screen between 25,000 and 110,000 babies a year using the existing dried bloodspot cards. The specified conditions to be screened for include sickle cell anaemia (Hb SS), Hb SC disease, Hb S/beta thalassaemia, Hb S/D(Punjab) and Hb S/O(Arab). Data are reported on screening results by ethnic group and geographical area. RESULTS: The prevalence of screen positive results across England is 1:2000. There is a 25-fold variation by geographical area. African babies make up 61% of all screen positive results despite representing only 4% of total births. Combined carrier rates vary widely by ethnicity, from 1.85 per 1000 (1:540) in 'White British' to 145 per 1000 (1:7) in 'African' babies. Refusal rates for screening show variation by ethnicity. CONCLUSIONS: These results provide useful information both about the frequency of these conditions and the carrier state and their geographic and ethnic distribution across England. This can be used to refine counselling information and are also useful to target and plan services and public information. PMID- 20591913 TI - FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma. AB - AIMS: To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations. METHOD: Dual colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. A third MYC probe was used to verify cases showing homozygous deletion. Eight equivocal biopsies were used for assay testing. RESULTS: Cut-off values for p16/CDKN2A deletion were calculated based on FISH signalling patterns obtained from the benign controls (mean percent nuclei plus three standard deviations). Hemizygous deletion was defined as >44% of nuclei showing the hemizygous (one p16/CDKN2A, two CEP-9 signals) or >15% of nuclei showing the monosomy (one p16/CDKN2A, one CEP-9 signal) deletion patterns. None of the benign cases showed a homozygous deletion pattern (no p16/CDKN2A, at least one CEP-9 signal). In the malignant cases, the percentage of nuclei showing homozygous deletion ranged from 1% to 87%. Therefore, the cut-off value for homozygous deletion was defined as >10%. P16/CDKN2A deletion was detected in 61% (33/54) of MPM cases. Among the equivocal biopsies, four showed homozygous and one showed hemizygous p16/CDKN2A deletion. Age over 60 years, asbestos exposure and p16/CDKN2A deletion were associated with a worse prognosis. CONCLUSION: Distinction between benign and malignant mesothelial proliferations can be diagnostically challenging. FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM. PMID- 20591914 TI - E-cadherin immunoexpression patterns in the characterisation of gastric carcinoma histotypes. AB - AIMS: E-cadherin, the main epithelial intercellular adhesion molecule, is abnormally expressed in many cancer types, including gastric carcinoma, which is the second leading cause of cancer death worldwide. The aim of this study was to contribute to the characterisation of gastric carcinoma histotypes based on a new approach to E-cadherin immunoexpression. METHODS: 97 gastric tumour samples obtained from the files of the Hospital of Cancer/Cancer Institute of Ceara, Brazil, were histologically analysed and classified as intestinal (n=40), diffuse (n=34), mixed (n=16) or unclassified (n=7) carcinomas. Immunohistochemistry was performed on the tissue microarray sections. Scores were applied according to the system of Jawhari: 0, no staining; 1, cytoplasmic staining; 2, cytoplasmic and membranous staining in the same case; 3, normal membranous immunoexpression; abnormal patterns: scores 0, 1 and 2; normal pattern: score 3. Jawhari scores were then evaluated utilising another approach: the absence of membranous expression scores (0 and 1) versus the presence of membranous expression (scores 2 and 3). RESULTS: A significant association between membranous expression of E cadherin and the intestinal histotype (36/40 (90%), and 28/41 (68%) for other histotypes) was found, while diffuse carcinomas were related to the absence of membranous expression. A very strong and peculiar relationship was observed between cytoplasm-exclusive E-cadherin expression (score 1) and the diffuse component of mixed tumours (11/16 (69%)). CONCLUSIONS: E-cadherin immunoexpression patterns help us to characterise gastric carcinoma histotypes. The presence or absence of membranous staining is the most valuable criterion in evaluating E-cadherin expression. Mixed tumours show a characteristic E-cadherin cytoplasmic expression in gastric carcinomas. PMID- 20591915 TI - Application of a novel and low cost technique to construct paraffin tissue microarrays out of paraffinised needle biopsy specimens from patients with breast cancer. AB - BACKGROUND: Paraffin tissue microarrays (TMAs) are a well accepted tool in pathology for high throughput molecular profiling, quality control and clinicopathological trials. No reports on TMAs constructed from paraffinised needle biopsy specimens (PNBSs) derived from patients with breast cancer can be found in the literature. PNBSs are sometimes the only source for tumour characterisation important for treatment. AIM: To develop a novel and low cost technique to construct TMAs from PNBSs (PNBSs-TMAs) in order to close this gap in TMA technology. METHODS: Using a skin biopsy punch, tumour-bearing parts of 84 PNBSs were punched out of the donor blocks, freed from the surrounding paraffin by melting and manually transferred into the preformed holes in the recipient block. After filling the holes, the PNBSs-TMA was fixed to a double sided adhesive tape and completely melted. Quality assessment of this new technique was performed comparing the HER2 status (synonym: cerbB2) of the PNBSs-TMA with the results of the original PNBSs and a TMA harbouring the tumour in corresponding resection and mastectomy specimens (RM-TMA). RESULTS: A 187-hole PNBSs-TMA with 84 PNBSs was successfully constructed. About 1% of the included PNBSs displayed signs of rolling and folding or of floating off the slide during the staining procedure. The results of immunohistochemistry, fluorescence in situ hybridisation and automated brightfield double in situ hybridisation showed high quality standard of the PNBSs-TMA, suitable for precise tumour profiling. CONCLUSIONS: PNBSs-TMAs are suitable for clinicopathological trials, especially those in which PNBSs are the only tumour source. PMID- 20591916 TI - More than just counting eosinophils: proximal oesophageal involvement and subepithelial sclerosis are major diagnostic criteria for eosinophilic oesophagitis. AB - BACKGROUND: According to American Gastroenterological Association Institute criteria, the diagnosis of eosinophilic oesophagitis (EOE) requires clinicopathological correlation. In the appropriate clinical context, a high eosinophil count (HEC, defined as >or=15/HPF) is considered pathological evidence of EOE. However, HEC may not always be identified in biopsies given its patchy distribution, and there may be histological overlap between EOE and gastro oesophageal reflux disease (GORD) in the distal oesophagus. AIMS: To evaluate the utility of subepithelial sclerosis and HEC in proximal oesophageal biopsies as additional diagnostic criteria. METHODS: Cases between 2004 and 2008 with paired proximal and distal oesophageal biopsies and the mention of eosinophils in the reports were retrieved from PathWest Queen Elizabeth II Medical Centre archives. Biopsies were reviewed and assessed for eosinophilic count and presence of subepithelial stroma and sclerosis. A final diagnosis was made after review of both biopsy and clinical details. RESULTS: There were 23 cases of EOE and 20 cases of GORD in an adult cohort. In comparison to GORD, cases of EOE had significantly higher eosinophil counts in proximal (39.4 vs 0.6 eosinophils/HPF) and distal biopsies (35.6 vs 1.9), with HEC in proximal biopsies a feature exclusive to EOE (83% vs 0%). Subepithelial sclerosis was identified in at least one biopsy in 74% of EOE and in only a single case of GORD. CONCLUSIONS: HEC in proximal oesophageal biopsies and subepithelial sclerosis should be considered major diagnostic findings in EOE. PMID- 20591917 TI - Incontinentia pigmenti with ultrastructurally disordered leucocytes. AB - Incontinentia pigmenti (IP) is a rare X-linked genodermatosis in which skin changes are combined with anomalies of other tissues, mainly of ectodermal origin. Mutations of the IKBKG gene are responsible for IP. Haematological disorders among IP patients are rare. Four female patients from a single family, with typical clinical characteristics of IP, are reported. In addition, all affected family members show a distinct haematological phenotype: hypogranular granulocytes, leucocytes with pseudoplatelets, and different anomalies of nuclei. Pseudoplatelets are a typical finding in patients with leukaemia. As there is dysfunction of the IKBKG gene in leukaemia, it is hypothesised that mis regulation of the NEMO pathway may cause the appearance of pseudoplatelets in acute leukaemias as well as in IP. These observations suggest that IP may not be only linked to skin and organs of the ectodermal origin. PMID- 20591918 TI - Nerve fibre colonisation by benign glands: word of caution. PMID- 20591919 TI - A rapid scoring technique for HER2 assessment following silver in situ hybridisation is accurate, robust and reliable. PMID- 20591920 TI - Simultaneous occurrence of Warthin-like papillary carcinoma and lymphoma of the mucosa associated lymphoid tissue in Hashimoto thyroiditis. PMID- 20591921 TI - An unusual breast malignant peripheral nerve sheath tumour and review of the literature. PMID- 20591922 TI - Homosexuality: mental health and quality of life in a Brazilian socio-cultural context. AB - BACKGROUND: The following study has focused on the production of empirical knowledge regarding homosexuality in the Brazilian social-cultural context. Little is known about this population in Brazil or in others in Latin America. AIMS: Investigation and comparison of prevalence of mental disorder, search for mental health services and quality of life between a group of homosexual individuals and a heterosexual control group. METHODS: A cross-sectional study, using 'snowball' sampling was carried out in order to form both groups, matched according to gender, age and educational degree. INSTRUMENTS: Data were gathered in individual interviews, through the Brazilian versions of MINI Plus and WHOQOL Bref. Statistical analysis was used to identify frequencies and make comparisons concerning the dimensions that were investigated. CONCLUSION: A higher prevalence of mental disturbance and attendance at mental health services by the homosexual group was verified, when compared to the control. The negative impact on the mental health of homosexuals as a result of discrimination in the Brazilian socio cultural context is suggested. PMID- 20591923 TI - Gender differences in the knowledge, attitude and practice towards mental health illness in a rapidly developing Arab society. AB - BACKGROUND: Mental disorders are common in all countries and cause immense suffering. Both gender and low socioeconomic status have been related to depression and other common mental disorders, but their possible relationship to mental health literacy remains uncertain. AIM: The aim of this study was to determine the gender differences in knowledge, attitudes and practices towards mental illness in a sample of Qatari and other Arab expatriates residing in the State of Qatar. DESIGN: This is a cross-sectional survey. SETTING: Primary healthcare centres in the State of Qatar. SUBJECTS: A multi-stage sampling design was used and a representative sample of 3,300 Qatari and other Arab expatriates above 20 years of age were surveyed during the period from October 2008 to June 2009. Of the study sample of 3,300, 2,514 subjects (76.2%) expressed their consent to participate. METHODS: A questionnaire was designed to assess the gender difference in knowledge, attitudes and practice towards mental illness.This questionnaire was administered to the Arab adult population above 20 years of age who were attending primary healthcare centres for various reasons other than mental illness. Face-to-face interviews were based on this questionnaire, which included variables on socio-demographic characteristics, knowledge, attitude and practice towards mental illness. RESULTS: Of the study sample, 49.2% were men and 50.8% were women. Overall, the studied women held more to the cultural beliefs related to some aspects of mental illness. For example, more women than men believed that mental illness is due to possession by evil spirits. Also, nearly half of the women thought traditional healers can treat mental illness; this belief was significantly lower in men. Some of the women considered people with mental illness as dangerous; a belief also significantly lower in men. Men had a better attitude towards mental illness than women. Men were more willing to visit a psychiatrist for their emotional problems, while women preferred a traditional healer. Women were more afraid than men to talk to the mentally ill. Knowledge of common mental illnesses was generally poor, and it seemed to be lower among women. Men obtained more information than women from the media; women favoured healthcare staff more than men did. CONCLUSION: The study reveals that men had better knowledge, beliefs and attitudes towards mental illness than women. Most of the women were afraid and not willing to keep friendships with the mentally ill. The results of this study underline the importance of information in changing people's attitude towards mental illness. Recognition of common mental disorders was very poor in men and women. PMID- 20591924 TI - Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release. AB - In vertebrates, a rise in intracellular free Ca(2+) (Ca(2+)(i)) levels during fertilization initiates second metaphase (mII) exit and the developmental programme. The Ca(2+) rise has long been considered to be crucial for development, but verifying this contribution would benefit from defining its role during fertilization. Here, we delineate the role of Ca(2+) release during mII exit in wild-type mouse eggs and show that it is dispensable for full-term development. Exit from mII can be induced by Zn(2+)-specific sequestration without Ca(2+) release, eliciting Cyclin B degradation in a manner dependent upon the proteasome pathway and intact microtubules, but not accompanied by degradation of the meiotic regulator Emi2. Parthenogenotes generated by Zn(2+) sequestration developed in vitro with normal expression of Ca(2+)-sensitive genes. Meiotic exit induced by either Ca(2+) oscillations or a single Ca(2+) rise in oocytes containing a signaling-deficient sperm resulted in comparable developmental rates. In the absence of Ca(2+) release, full-term development occurred approximately 50% less efficiently, but at readily detectable rates, with the birth of 27 offspring. These results show in intact mouse oocytes that Zn(2+) is essential for mII arrest and suggest that triggering meiotic exit is the sole indispensable developmental role of Ca(2+) signaling in mammalian fertilization. PMID- 20591926 TI - Nickel-titanium wire as a flexor tendon suture material: an ex vivo study. AB - Nickel-titanium shape memory alloy (NiTi) is a new suture material that is easy to handle, is strong, and biocompatible. The purpose of this study was to evaluate the material properties and biomechanical behaviour of 150 microm and 200 microm NiTi wires in flexor tendon repair. Braided polyester (4-0 Ethibond) was used as control. Fifty fresh-frozen porcine flexor tendons were repaired using the Pennington modification of the Kessler repair or a double Kessler technique. NiTi wires were stiffer and reached higher tensile strength compared to braided polyester suture. Repairs with 200 microm NiTi wire had a higher yield force, ultimate force and better resistance to gapping than 4-0 braided polyester repairs. Repairs made with 200 microm NiTi wire achieved higher stiffness and ultimate force than repairs made with 150 microm NiTi wire. PMID- 20591927 TI - Pyrocarbon implant fracture after metacarpophalangeal joint arthroplasty: an unusual cause for early revision. PMID- 20591928 TI - Compound osteosynthesis in a metastatic fracture of the radius shaft. PMID- 20591929 TI - Distraction external fixation for comminuted fractures of the base of the proximal phalanx. PMID- 20591930 TI - Unicondylar phalangeal fracture reduction using a sponge-holding forceps: a safe and effective technique. PMID- 20591931 TI - Self-rejuvenation of the hand. PMID- 20591932 TI - The discount store artificial nail: an ideal splint for nail bed repairs. PMID- 20591933 TI - A new variant of four-strand tendon repairs. PMID- 20591934 TI - Staged flexor tendon reconstruction in a patient with caseous tuberculous tenosynovitis. PMID- 20591935 TI - Mycobacterium xenopi flexor tenosynovitis. PMID- 20591937 TI - Re: Howard et al. A prospective randomised trial of absorbable vs. non-absorbable sutures for wound closure after fasciectomy for Dupuytren's contracture. J Hand Surg Eur. 2009, 34: 618-20. PMID- 20591936 TI - Locked metacarpophalangeal joint associated with PAX2 gene mutation: a case report. PMID- 20591940 TI - Intrarenal urothelium proliferation: an unexpected early event following ischemic injury. AB - Identification of renal cell progenitors and recognition of the events contributing to cell regeneration following ischemia-reperfusion injury (IRI) are a major challenge. In a mouse model of unilateral renal IRI, we demonstrated that the first cells to proliferate within injured kidneys were urothelial cells expressing the progenitor cell marker cytokeratin 14. A systematic cutting of the injured kidney revealed that these urothelial cells were located in the deep cortex at the corticomedullary junction in the vicinity of lobar vessels. Contrary to multilayered bladder urothelium, these intrarenal urothelial cells located in the upper part of the medulla constitute a monolayered barrier and express among uroplakins only uroplakin III. However, like bladder progenitors, intrarenal urothelial cells proliferated through a FGF receptor-2 (FGFR2) mediated process. They strongly expressed FGFR2 and proliferated in vivo after recombinant FGF7 administration to control mice. In addition, IRI led to FGFR phosphorylation together with the selective upregulation of FGF7 and FGF2. Conversely, by day 2 following IRI, renal urothelial cell proliferation was significantly inhibited by FGFR2 antisense oligonucleotide administration into an intrarenal urinary space. Of notice, no significant migration of these early dividing urothelial cells was detected in the cortex within 7 days following IRI. Thus our data show that following IRI, proliferation of urothelial cells is mediated by the FGFR2 pathway and precedes tubular cell proliferation, indicating a particular sensitivity of this structure to changes caused by the ischemic process. PMID- 20591941 TI - Progressive renal papillary calcification and ureteral stone formation in mice deficient for Tamm-Horsfall protein. AB - Mammalian urine contains a range of macromolecule proteins that play critical roles in renal stone formation, among which Tamm-Horsfall protein (THP) is by far the most abundant. While THP is a potent inhibitor of crystal aggregation in vitro and its ablation in vivo predisposes one of the two existing mouse models to spontaneous intrarenal calcium crystallization, key controversies remain regarding the role of THP in nephrolithiasis. By carrying out a long-range follow up of more than 250 THP-null mice and their wild-type controls, we demonstrate here that renal calcification is a highly consistent phenotype of the THP-null mice that is age and partially gene dosage dependent, but is gender and genetic background independent. Renal calcification in THP-null mice is progressive, and by 15 mo over 85% of all the THP-null mice develop spontaneous intrarenal crystals. The crystals consist primarily of calcium phosphate in the form of hydroxyapatite, are located more frequently in the interstitial space of the renal papillae than intratubularly, particularly in older animals, and lack accompanying inflammatory cell infiltration. The interstitial deposits of hydroxyapatite observed in THP-null mice bear strong resemblances to the renal crystals found in human kidneys bearing idiopathic calcium oxalate stones. Compared with 24-h urine from the wild-type mice, that of THP-null mice is supersaturated with brushite (calcium phosphate), a stone precursor, and has reduced urinary excretion of citrate, a stone inhibitor. While less frequent than renal calcinosis, renal pelvic and ureteral stones and hydronephrosis occur in the aged THP-null mice. These results provide direct in vivo evidence indicating that normal THP plays an important role in defending the urinary system against calcification and suggest that reduced expression and/or decreased function of THP could contribute to nephrolithiasis. PMID- 20591942 TI - Computational prosodic markers for autism. AB - We present results obtained with new instrumental methods for the acoustic analysis of prosody to evaluate prosody production by children with Autism Spectrum Disorder (ASD) and Typical Development (TD). Two tasks elicit focal stress - one in a vocal imitation paradigm, the other in a picture-description paradigm; a third task also uses a vocal imitation paradigm, and requires repeating stress patterns of two-syllable nonsense words. The instrumental methods differentiated significantly between the ASD and TD groups in all but the focal stress imitation task. The methods also showed smaller differences in the two vocal imitation tasks than in the picture-description task, as was predicted. In fact, in the nonsense word stress repetition task, the instrumental methods showed better performance for the ASD group. The methods also revealed that the acoustic features that predict auditory-perceptual judgment are not the same as those that differentiate between groups. Specifically, a key difference between the groups appears to be a difference in the balance between the various prosodic cues, such as pitch, amplitude, and duration, and not necessarily a difference in the strength or clarity with which prosodic contrasts are expressed. PMID- 20591946 TI - Medicalisation of ageing: plastic people. PMID- 20591949 TI - Cross border regulation of doctors. PMID- 20591951 TI - National audit of care after mastectomy points to need for better information on reconstruction. PMID- 20591952 TI - UN launches commission on HIV to look at discrimination and legal barriers to treatment. PMID- 20591953 TI - Cardiologist let his ambition interfere with patients' best interests, GMC is told. PMID- 20591956 TI - Screening accuracy of Level 2 autism spectrum disorder rating scales. A review of selected instruments. AB - The goal of this review was to examine the state of Level 2, caregiver-completed rating scales for the screening of Autism Spectrum Disorders (ASDs) in individuals above the age of three years. We focused on screening accuracy and paid particular attention to comparison groups. Inclusion criteria required that scales be developed post ICD-10, be ASD-specific, and have published evidence of diagnostic validity in peer-reviewed journals. The five scales reviewed were: the Social Communication Questionnaire (SCQ), Gilliam Autism Rating Scale/Gilliam Autism Rating Scale-Second Edition (GARS/GARS-2), Social Responsiveness Scale (SRS), Autism Spectrum Screening Questionnaire (ASSQ), and Asperger Syndrome Diagnostic Scale (ASDS). Twenty total studies were located, most examining the SCQ. Research on the other scales was limited. Comparisons between scales were few and available evidence of diagnostic validity is scarce for certain subpopulations (e.g., lower functioning individuals, PDDNOS). Overall, the SCQ performed well, the SRS and ASSQ showed promise, and the GARS/GARS-2 and ASDS demonstrated poor sensitivity. This review indicates that Level 2 ASD caregiver completed rating scales are in need of much more scientific scrutiny. PMID- 20591957 TI - Visual influences on speech perception in children with autism. AB - The bimodal perception of speech sounds was examined in children with autism as compared to mental age-matched typically developing (TD) children. A computer task was employed wherein only the mouth region of the face was displayed and children reported what they heard or saw when presented with consonant-vowel sounds in unimodal auditory condition, unimodal visual condition, and a bimodal condition. Children with autism showed less visual influence and more auditory influence on their bimodal speech perception as compared to their TD peers, largely due to significantly worse performance in the unimodal visual condition (lip reading). Children with autism may not benefit to the same extent as TD children from visual cues such as lip reading that typically support the processing of speech sounds. The disadvantage in lip reading may be detrimental when auditory input is degraded, for example in school settings, whereby speakers are communicating in frequently noisy environments. PMID- 20591958 TI - Increasing social responsiveness in a child with autism. A comparison of music and non-music interventions. AB - This study sought to determine the effects of using music and non-music interventions on the social responsive and avoidant behaviours of a preschool child with autism. A single-subject alternating treatment design was used in which two interventions were presented in a similar fashion except for the addition of music during the music condition. Four phases took place: baseline (Phase A), alternating treatments (Phase B), a second treatment phase (Phase C) using the condition that proved to be more effective in Phase B, and follow-up (Phase D). Data were collected over a total of 12 treatment sessions for various social responsive and avoidant behaviours. Results indicated that the music intervention was more effective than the non-music intervention in increasing all three social responsive behaviours in both Phases B and C. Furthermore, no avoidant behaviours were observed during the music condition. It is suggested that the music condition was more motivating for the participant than the non music condition, resulting in more social responsive behaviours. PMID- 20591959 TI - Brief report: Electroconvulsive therapy for malignant catatonia in an autistic adolescent. AB - A 14-year-old male with autism and mild mental retardation developed malignant catatonia characterized by classic symptoms of catatonia, bradycardia and hypothermia. Bilateral electroconvulsive therapy and lorazepam were required for resolution. The case expands the occurrence of catatonia in autism into its malignant variant. PMID- 20591960 TI - How parents perceive and feel about participation in community activities. The comparison between parents of preschoolers with and without Autism Spectrum Disorders. AB - The present study compared how parents of preschoolers with and without Autism Spectrum Disorders (ASD) perceived and felt about participation in community activities. A questionnaire survey was conducted with 380 Hong Kong parents of preschoolers with ASD and 214 Hong Kong parents of preschoolers without ASD. The two groups were not different in their willingness and frequency of participation in community activities. However, the psychological processes underneath their willingness were very different. Among the parents of preschoolers with ASD, their willingness was associated with how they perceived the difficulty and importance of the participation and what emotions they experienced during the activities. This pattern of association was not evident among the parents of preschoolers without ASD. PMID- 20591961 TI - Towards more uniform conflict disclosures: the updated ICMJE conflict of interest reporting form. PMID- 20591962 TI - A patient with CLL and a dry cough. PMID- 20591965 TI - Huntington's disease. PMID- 20591966 TI - Investigating symmetrical polyarthritis of recent origin. PMID- 20591967 TI - Patient choice minus the ulterior motive. PMID- 20591970 TI - Can mammalian mothers influence the sex of their offspring peri-conceptually? AB - Although controversial, growing evidence from evolutionary biology suggests that the mammalian mother may have a role in influencing the sex of her offspring. However, there is competing information on the molecular mechanisms by which such influence could be manifested. The new initiatives are based on hypotheses from evolutionary biology: the 'good condition' hypothesis, which suggests that post conception, higher levels of maternal glucose may differentially promote the development of male embryos; and the 'maternal dominance' hypothesis, which proposes that before conception, higher follicular testosterone may influence the development of the ovum so that it emerges already adapted to receive an X- or a Y-chromosome-bearing spermatozoon. Now, it seems these hypothesised mechanisms could be operating in synchrony, each complementing and reinforcing the other. On the other hand, there are continuing problems in identifying a precise sequence of mechanisms as evidenced from research in sperm-sorting. Research on high-fat diets and the sex ratio in polytocous species may indicate important differences in proximate mechanisms for sex allocation between polytocous and monotocous mammals. PMID- 20591971 TI - Gene-environment interaction for hypertension among African American women across generations. AB - African American women have the highest prevalence of hypertension and obesity of any group in the United States. African American girls have the highest incidence of obesity of any groups of children in the nation, and diagnoses of hypertension have been rising among this group. Because both genetic heredity and body mass index (BMI) are important risk factors for hypertension, this study examined the gene-BMI interaction for hypertension across the lifespan in two generations of African American women. Participants comprised of 868 African American women in the parent cohort and 322 in the offspring cohort from the Hypertension Genetic Epidemiology Network (HyperGEN) study, part of the Family Blood Pressure Program (FBPP). A total of 115 single-nucleotide polymorphisms (SNPs) were evaluated among the parent cohort and 491 among the offspring cohort for tests of SNP-BMI interaction using methods of false discovery rate (FDR; <.20) and examination of minor allele frequency (MAF; >.05) and Hardy-Weinberg equilibrium (>.10). One SNP (located in the CAPN 13 gene, rs1879282) passed adjustments for the multiple testing mentioned above and had a significant (p < .01) gene-BMI interaction on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) among African American female offspring. The rs1879282 SNP is located on chromosome 2 on the calpain (CAPN) 13 gene, which is part of a family of cytosolic calcium activated proteases involved in apoptosis, cell division, modulation of integrin cytoskeletal interactions, and synaptic plasticity. This SNP was not available for testing in the African American parent cohort. PMID- 20591972 TI - Isolated GH deficiency type II: knockdown of the harmful Delta3GH recovers wt-GH secretion in rat tumor pituitary cells. AB - Isolated GH deficiency type II (IGHD II) is the autosomal dominant form of GHD. In the majority of the cases, this disorder is due to specific GH-1 gene mutations that lead to mRNA missplicing and subsequent loss of exon 3 sequences. When misspliced RNA is translated, it produces a toxic 17.5-kDa GH (Delta3GH) isoform that reduces the accumulation and secretion of wild-type-GH. At present, patients suffering from this type of disease are treated with daily injections of recombinant human GH in order to maintain normal growth. However, this type of replacement therapy does not prevent toxic effects of the Delta3GH mutant on the pituitary gland, which can eventually lead to other hormonal deficiencies. We developed a strategy involving Delta3GH isoform knockdown mediated by expression of a microRNA-30-adapted short hairpin RNA (shRNA) specifically targeting the Delta3GH mRNA of human (shRNAmir-Delta3). Rat pituitary tumor GC cells expressing Delta3GH upon doxycycline induction were transduced with shRNAmir-Delta3 lentiviral vectors, which significantly reduced Delta3GH protein levels and improved human wild-type-GH secretion in comparison with a shRNAmir targeting a scrambled sequence. No toxicity due to shRNAmir expression could be observed in cell proliferation assays. Confocal microscopy strongly suggested that shRNAmir Delta3 enabled the recovery of GH granule storage and secretory capacity. These viral vectors have shown their ability to stably integrate, express shRNAmir, and rescue IGHD II phenotype in rat pituitary tumor GC cells, a methodology that opens new perspectives for the development of gene therapy to treat IGHD patients. PMID- 20591973 TI - CYP24A1 inhibition enhances the antitumor activity of calcitriol. AB - High systemic exposures to calcitriol are necessary for optimal antitumor effects. Human prostate cancer PC3 cells are insensitive to calcitriol treatment. Therefore, we investigated whether the inhibition of 24-hydroxylase (CYP24A1), the major calcitriol inactivating enzyme, by ketoconazole (KTZ) or RC2204 modulates calcitriol serum pharmacokinetics and biologic effects. Dexamethasone (Dex) was added to minimize calcitriol-induced hypercalcemia and as a steroid replacement for the KTZ inhibition of steroid biosynthesis cytochrome P450 enzymes. KTZ effectively inhibited time-dependent calcitriol-inducible CYP24A1 protein expression and enzyme activity in PC3 cells and C3H/HeJ mouse kidney tissues. Systemic calcitriol exposure area under the curve was higher in mice treated with a combination of calcitriol and KTZ than with calcitriol alone. KTZ and Dex synergistically potentiated calcitriol-mediated antiproliferative effects in PC3 cells in vitro; this effect was associated with enhanced apoptosis. After treatment with calcitriol and KTZ/Dex, although caspase-9 and caspase-3 were not activated and cytochrome c was not released by mitochondria, caspase-8 was activated and the truncated Bid protein level was increased. Translocation of apoptosis-inducing factor to the nucleus was observed, indicating a role of the apoptosis-inducing factor-mediated and caspase-independent apoptotic pathways. Calcitriol and KTZ/Dex combination suppressed the clonogenic survival and enhanced the growth inhibition observed with calcitriol alone in PC3 human prostate cancer xenograft mouse model. Our results show that the administration of calcitriol in combination with CYP24A1 inhibitor enhances antiproliferative effects, increases systemic calcitriol exposure, and promotes the activation of caspase-independent apoptosis pathway. PMID- 20591974 TI - Molecular signature of mineralocorticoid receptor signaling in cardiomyocytes: from cultured cells to mouse heart. AB - Excess mineralocorticoid signaling is deleterious for cardiovascular functions, as demonstrated by the beneficial effects of mineralocorticoid receptor (MR) antagonism on morbidity and mortality in patients with heart failure. However, the understanding of signaling pathways after MR activation in the heart remains limited. We performed transcriptomic analyses in the heart of double-transgenic mice with conditional, cardiomyocyte-specific, overexpression of the MR (MRcardio mice) or the glucocorticoid receptor (GR; GRcardio mice). Some of the genes induced in MRcardio mice were selected for comparative evaluation (real time PCR) in vivo in the heart of mice and ex vivo in the MR-expressing cardiomyocyte H9C2 cell line after aldosterone or corticosterone treatment. We demonstrate that chronic MR overexpression in the heart results in a limited number of induced (n = 24) and repressed (n = 22) genes compared with their control littermates. These genes are specifically modulated by MR because there is limited overlap (three induced, four repressed) with the genes that are regulated in the heart of GRcardio mice (compared with control mice: 70 induced, 73 repressed). Interestingly, some MR-induced genes that are up-regulated in vivo in mice are also induced by 24-h aldosterone treatment in H9C2 cells, such as plasminogen activator inhibitor 1 and Serpina-3 (alpha1-antichymotrypsin). The signaling pathways that are affected by long-term activation of MR may be of particular interest to design novel therapeutic targets in cardiac diseases. PMID- 20591975 TI - RhoA and DIAPH1 mediate adrenocorticotropin-stimulated cortisol biosynthesis by regulating mitochondrial trafficking. AB - Steroid hormones are formed by the successive action of enzymes that are localized in mitochondria and the endoplasmic reticulum (ER). Compartmentalization of these enzymes in different subcellular organelles dictates the need for efficient transfer of intermediary metabolites between the mitochondrion and ER; however, the molecular determinants that regulate interorganelle substrate exchange are unknown. The objective of this study was to define the molecular mechanism by which adrenocorticotropin (ACTH) signaling regulates communication between mitochondria and the ER during steroidogenesis. Using live cell video confocal microscopy, we found that ACTH and dibutyryl cAMP rapidly increased the rate of mitochondrial movement. Inhibiting tubulin polymerization prevented both basal and ACTH/cAMP-stimulated mitochondrial trafficking and decreased cortisol secretion. This decrease in cortisol secretion evoked by microtubule inhibition was paralleled by an increase in dehydroepiandrosterone production. In contrast, treatment with paclitaxel to stabilize microtubules or latrunculin B to inhibit actin polymerization and disrupt microfilament organization increased both mitochondrial trafficking and cortisol biosynthesis. ACTH-stimulated mitochondrial movement was dependent on RhoA and the RhoA effector, diaphanous-related homolog 1 (DIAPH1). ACTH signaling temporally increased the cellular concentrations of GTP-bound and Ser-188 phosphorylated RhoA, which promoted interaction with DIAPH1. Expression of a dominant-negative RhoA mutant or silencing DIAPH1 impaired mitochondrial trafficking and cortisol biosynthesis and concomitantly increased the secretion of adrenal androgens. We conclude that ACTH regulates cortisol production by facilitating interorganelle substrate transfer via a process that is mediated by RhoA and DIAPH1, which act to coordinate the dynamic trafficking of mitochondria. PMID- 20591976 TI - Periovulatory leukocyte infiltration in the rat ovary. AB - Ovulation is preceded by intraovarian inflammatory reactions that occur in response to the preovulatory gonadotropin surge. As a main inflammatory event, leukocytes infiltrate the ovary and release proteolytic enzymes that degrade the extracellular matrix weakening the follicular wall, a required step for follicle rupture. This study aimed to quantitatively measure the infiltrating leukocytes, determine their cell types, and localize infiltration sites in the periovulatory rat ovary. Cycling adult and gonadotropin-stimulated immature rats were used as animal models. Ovaries were collected at five different stages of estrous cycle in the adult rats (diestrus, 1700 h; proestrus, 1500 h; proestrus, 2400 h; estrus, 0600 h; and metestrus, 1700 h) and at five different time points after superovulation induction in the immature rats (pregnant mare's serum gonadotrophin, 0 h; pregnant mare's serum gonadotrophin, 48 h; human chorionic gonadotropin, 6 h; human chorionic gonadotropin, 12 h; and human chorionic gonadotropin, 24 h). The ovaries were either dissociated into a single cell suspension for flow cytometric analysis or fixed for immunohistochemical localization of the leukocytes. Similar numbers of leukocytes were seen throughout the estrous cycle (approximately 500,000/ovary), except proestrus 2400 when 2-fold higher numbers of leukocytes were found (approximately 1.1 million/ovary). A similar trend of periovulatory rise of leukocyte numbers was seen in the superovulation-induced immature rat model, recapitulating a dramatic increase in leukocyte numbers upon gonadotropin stimulation. Both macrophage/granulocytes and lymphocytes were among the infiltrating leukocytes and were localized in the theca and interstitial tissues, where platelet endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1 may play roles in the transmigration of leukocytes, because their expressions correlates spatiotemporally with the infiltrating leukocytes. In addition, a strong inverse relationship between leukocyte numbers in the ovary and spleen, as well as significant reduction of leukocyte infiltration in the splenectomized rats, were seen, indicating that the spleen may serve as an immediate supplier of leukocytes to the periovulatory ovary. PMID- 20591977 TI - Role of GABAergic neurones in the nucleus tractus solitarii in modulation of cardiovascular activity. AB - GABAergic neurones are interspersed throughout the nucleus tractus solitarii (NTS), and their tonic activity is crucial to the maintenance of cardiorespiratory homeostasis. However, the mechanisms that regulate the magnitude of GABAergic inhibition in the NTS remain unknown. We hypothesized that the level of GABAergic inhibition is proportionally regulated by the level of excitatory synaptic input to the NTS from baroreceptors. Using the in situ working heart-brainstem preparation in normotensive and spontaneously hypertensive rats, we blocked GABA(A) receptor-mediated neurotransmission in the NTS with gabazine (a specific GABA(A) receptor antagonist) at two levels of perfusion pressure (low PP, 60-70 mmHg; and high PP, 105-125 mmHg) while monitoring the immediate changes in cardiorespiratory variables. In normotensive rats, gabazine produced an immediate bradycardia consistent with disinhibition of NTS circuit neurones that regulate heart rate (HR) which was proportional to the level of arterial pressure (HR at low PP, 57 +/- 9 beats min(1); at high PP, 177 +/- 9 beats min(1); P < 0.001), suggesting that GABAergic circuitry in the NTS modulating heart rate was arterial pressure dependent. In contrast, there was no significant difference in the magnitude of gabazine-induced bradycardia in spontaneously hypertensive rats at low or high PP (HR at low PP, 45 +/- 10 beats min(1); at high PP, 58 +/- 7 beats min(1)). With regard to thoracic sympathetic nerve activity (tSNA), at high PP there was a significant reduction in tSNA during the inspiratory (I) phase of the respiratory cycle, but only in the normotensive rat (tSNA = 18.7 +/- 10%). At low PP, gabazine caused an elevation of the postinspiration phase of tSNA in both normotensive (tSNA = 23.7 +/- 2.9%) and hypertensive rats (tSNA = 44.2 +/- 14%). At low PP, gabazine produced no change in tSNA during the mid-expiration phase in either rat strain, but at high PP we observed a significant reduction in the mid-expiration phase tSNA, but only in the spontaneously hypertensive rat (tSNA = 25.2 +/- 8%). Gabazine at both low and high PP produced a reduction in the late expiration phase of tSNA in the hypertensive rat (low PP, tSNA = 29.4 +/- 4.4%; high PP, tSNA = 22.8 +/- 3%), whereas in the normotensive rat this was only significant at high PP (tSNA = 42.5 +/- 6.1%). Therefore, in the spontaneously hypertensive rat, contrary to the GABA(A) receptor-mediated control of HR, it appears that GABA(A) receptor mediated control of tSNA in the NTS is arterial pressure dependent. This study provides new insight into the origin of GABAergic inhibition in NTS circuitry affecting heart rate and sympathetic activity. PMID- 20591979 TI - High efficacy of concomitant treatment of undifferentiated (anaplastic) thyroid cancer with radiation and docetaxel. AB - CONTEXT: Anaplastic thyroid carcinoma (ATC) is a rare but aggressive solid tumor with a very short survival time even with multimodality treatment. In view of in vitro data and the high rate of p53 mutations in ATC, we have used combined treatment with external beam radiation and docetaxel. OBJECTIVE: The objective was to analyze the activity using radiation plus docetaxel. DESIGN: The design was a retrospective analysis. SETTING: The study was performed in a referral center of a university hospital. PATIENTS: A total of six patients with ATC were treated at our institution. INTERVENTION: Treatment consisted of standard external beam radiation of 60.0 Gy in 30 fractions along with docetaxel at a flat dose of 100 mg absolute every 3 wk for a total of six cycles starting within the first week of radiation. OUTCOME MEASURE: The outcome measure included clinical response and survival. RESULTS: Five patients completed radiochemotherapy. One patient has completed radiation but is still on treatment with docetaxel. Four patients achieved complete remission and two partial response. During radiation therapy, four patients developed severe mucositis/stomatitis and two dermatitis, necessitating hospitalization. Two patients developed pneumonia and one urinary tract infection. All patients were hospitalized for a median of 17 d (range, 4-40 d) because of toxicites. After a median follow up of 21.5 months (range, 2-40 months), five patients are alive. CONCLUSION: The preliminary data suggest that the combination of radiation and concomitant docetaxel is highly effective in patients with ATC. However, a formal phase II study is needed to assess the therapeutic potential of this combination. PMID- 20591978 TI - Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport. AB - In this study, we examined the effect of bicarbonate transporters on ammonium/ammonia uptake in the medullary thick ascending limb cell line ST-1. Cells were treated with 1 mm ouabain and 0.2 mM bumetanide to minimize carrier mediated NH(4)(+) transport, and the intracellular accumulation of (14)C methylammonium/methylammonia ((14)C-MA) was determined. In CO(2)/HCO(3)(-)-free solution, cells at normal pH briefly accumulated (14)C-MA over 7 min and reached a plateau. In CO(2)/HCO(3)(-) solution, however, cells markedly accumulated (14)C MA over the experimental period of 30 min. This CO(2)/HCO(3)(-)-dependent accumulation was reduced by the bicarbonate transporter blocker, 4,4 diisothiocyanatostilbene-2,2-disulfonate (DIDS; 0.5 mM). Replacing Cl(-) with gluconate reduced the accumulation, but the reduction was more substantial in the presence of DIDS. Incubation of cells at pH 6.8 (adjusted with NaHCO(3) in 5% CO(2)) for 24 h lowered the mean steady-state intracellular pH to 6.96, significantly lower than 7.28 for control cells. The presence of DIDS reduced (14)C-MA accumulation in control conditions but had no effect after acidic incubation. Immunoblotting showed that NBCn1 was upregulated after acidic incubation and in NH(4)Cl-containing media. The Cl(-)-HCO(3)(-) exchanger AE2 was present, but its expression remained unaffected by acidic incubation. Expressed in Xenopus oocytes, NBCn1 increased carrier-mediated (14)C-MA transport, which was abolished by replacing Na(+). Two-electrode voltage clamp of oocytes exhibited negligible current after NH(4)Cl application. These results suggest that DIDS-sensitive HCO(3)(-) extrusion normally governs NH(4)(+)/NH(3) uptake in the medullary thick ascending limb cells. We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport. PMID- 20591980 TI - Impact of heterozygosity for acid-labile subunit (IGFALS) gene mutations on stature: results from the international acid-labile subunit consortium. AB - CONTEXT: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. OBJECTIVE: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. SUBJECTS/METHODS: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type. Within each family, the effect of IGFALS mutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height sd score (HtSDS) were then pooled and evaluated. RESULTS: Mean HtSDS in 2ALS was -2.31 +/- 0.87 (less than -2 SDS in 62%); in 1ALS, -0.83 +/- 1.34 (less than -2 SDS in 26%); and in WT, -1.02 +/- 1.04 (less than -2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was -1.93 +/- 0.79; between 1ALS and WT, -0.90 +/- 1.53; and between 2ALS and 1ALS, -1.48 +/- 0.83. CONCLUSIONS: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system. PMID- 20591981 TI - The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism. AB - CONTEXT AND OBJECTIVE: Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder. DESIGN AND SETTING: Long-term follow up, including detailed clinical, biochemical, and genetic examinations, were performed and compared with those at diagnosis. PATIENTS: Patients included 10 men with AHH [serum testosterone (T) <125 ng/dl]. INTERVENTIONS: Overnight neuroendocrine studies, semen fluid analyses, and genetic screening were performed (KAL1, FGFR1, PROK2, PROKR2, NELF, TAC3, TACR3, and GNRH1) over a decade of longitudinal follow up. RESULTS: Follow-up evaluations were conducted 10.6 +/- 5.9 yr after initial studies and revealed that the clinical characteristics and seminal fluid analyses of AHH men (body mass index, 28.8 +/- 4.1 vs. 27.0 +/- 4.3 kg/m(2); testicular volume, 18 +/- 6 vs. 19 +/- 6 ml) do not change over a decade with no spontaneous reversals. Several men exhibited some variability in their endogenous GnRH-induced LH secretory patterns, including emergence of endogenous pulsatility in three individuals. However, all remained hypogonadal (T < or =130 ng/dl). A single heterozygous DNA sequence change in PROKR2 (V317L) was identified, although this rare sequence variant did not prove to be functionally abnormal in vitro. Seven days of pulsatile GnRH therapy in this subject nearly normalized his serum T, supporting that the site of the defect is hypothalamic and not pituitary. CONCLUSIONS: 1) AHH in men appears to be a long-lasting condition. 2) Although minor changes in the abnormal pattern of endogenous GnRH-induced LH secretion occurred in some AHH patients, all remained frankly hypogonadal. PMID- 20591982 TI - Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results. AB - CONTEXT: In our neonatal program, a number of infants with congenital hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of 20 mU/liter whole blood was used as a cutoff point. OBJECTIVE: The objective of the study was to find out prospectively the additional number of newborns with CH if the TSH cutoff point is lowered to 10 mU/liter. POPULATION AND METHODS: The study included 311,390 screened newborns. The children with CH were followed up for a period of 3 yr. RESULTS: Twenty-eight percent of infants diagnosed with CH had neonatal TSH values between 10 and 20 mU/liter (56 of 200). Forty of 47 infants, who were reevaluated later on (85.1%), suffered permanent CH. A thyroid scintiscan and/or echogram revealed that eight of 40 children (20.0%) had a structural defect, and the remaining (32 of 40) had a functional defect of the thyroid gland without anatomical abnormality; 14 of 32 cases were familial. Eighteen of the 47 reevaluated infants were prematurely born (38.3%) and 15 of these 18 had permanent CH (83.3%). The lowering of TSH cutoff point from 20 to 10 mU/liter resulted in a 10-fold increase of recall rate. CONCLUSIONS: A significant number of cases with permanent CH are missed when a TSH threshold of 20 mU/liter is applied. Almost 40% of the missed CH cases were premature. A mild increase of TSH at screening is not a predictor of transient CH. The increase in recall rate constitutes a serious drawback and should be balanced against the possible consequences of thyroid dysfunction at this important developmental stage. PMID- 20591983 TI - Insulin resistance in African-American and Caucasian women: differences in lipotoxicity, adipokines, and gene expression in adipose tissue and muscle. AB - OBJECTIVES: We tested whether African-American (AA) women are different from Caucasian women in regard to lipotoxicity, adipokines, and gene expression in adipose tissue and muscle. DESIGN: Insulin sensitivity (S(I)), plasma adipocytokine levels, intramyocellular lipid (IMCL), and the expression of candidate genes in adipose tissue and muscle were measured in AA and Caucasian women. SETTING: This study was performed in an ambulatory general clinical research center. SUBJECTS: Subjects were healthy, nondiabetic AA and Caucasian women. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: Comparison of S(I), IMCL, plasma adiponectin, and the expression of candidate genes regulating adipogenesis, lipogenesis, and inflammation in adipose tissue and muscle. RESULTS: AA had lower plasma adiponectin and IMCL when compared with Caucasian women with similar S(I). In sc adipose tissue (SAT), the expression of genes involved in adipogenesis including peroxisomal proliferator-activated receptor-gamma (PPARgamma) and lipin-1beta were also reduced in SAT of AA subjects (19%, P = 0.06, and 25%, P = 0.05, respectively). Similarly, 1 acylglycerol-3-phosphate acyltransferase 2 (AGPAT 2), stearoyl-coenzyme A desaturase-1 (SCD1), and CD36 mRNA expression was significantly reduced in SAT by 19, 54, and 28% respectively (P < 0.01 for all) in AA compared with Caucasian women. Yet the expression of CD68 in SAT was similar in both ethnic groups. Gene expression studies in muscle revealed a 31% reduction in expression of AGPAT 2 and a 72% reduction in SCD1 genes in AA. CONCLUSION: AA women demonstrated lower expression of several PPARgamma-responsive genes in adipose tissue, lower plasma adiponectin, and decreased IMCL levels as compared with Caucasians, which suggests that African-Americans may be protected from lipotoxicity. Together these data suggest significant ethnic differences in the pathophysiology of insulin resistance. PMID- 20591985 TI - Commentary: what can evidence on intergenerational transmission of risk of low birth weight and cardiovascular disease tell us about mechanisms? PMID- 20591984 TI - A nonlinear relationship of generalized and central obesity with diurnal cortisol secretion in the Whitehall II study. AB - CONTEXT: Evidence for an association of measures of generalized and central obesity with salivary cortisol secretion is equivocal. OBJECTIVE: The objective of this study was to assess the relationship between body mass index (BMI), waist circumference, and salivary cortisol. DESIGN: The design was a cross-sectional study of BMI, waist circumference, and salivary cortisol from phase 7 (2002-2004) of the Whitehall II study. SETTING: The occupational cohort was originally recruited in 1985-1988. PARTICIPANTS: Participants included 2915 men and 1041 women aged 50-74 yr with complete information on height, weight and waist circumference, and cortisol secretion. OUTCOME MEASURES: Saliva samples were taken on waking, waking plus 0.5, 2.5, 8, and 12 h, and bedtime for the assessment of cortisol. The cortisol awakening response and slope in diurnal secretion were calculated. RESULTS: After adjustment for age, sex, social position, waking time, and time since waking of sample collection, increasing central and generalized obesity was associated with lower waking cortisol (P = 0.001). U-shaped associations were apparent between diurnal slope in salivary cortisol and both BMI and waist circumference (P < 0.0001 for quadratic term). For example, the shallowest (most adverse) slopes in salivary cortisol were associated with highest (>31 kg/m(2)) and lowest (<21 kg/m(2)) levels of BMI, and the steepest slopes were apparent for those with BMI of 26 kg/m(2), independently of the 12 covariates examined. No associations were apparent for the cortisol awakening response (P > 0.05). CONCLUSION: The associations of measures of generalized and central obesity with diurnal slope in salivary cortisol are not linear in older adults. These nonlinear associations may explain previously described mixed findings. PMID- 20591986 TI - Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause? AB - BACKGROUND: There is a consensus that the large fluctuations in mortality seen in Russia in the past two decades can be attributed to trends in alcohol consumption. However, the precise mechanisms linking alcohol to mortality from circulatory disease remain unclear. It has recently been argued that a substantial number of such deaths currently ascribed to cardiovascular disorders are misclassified cases of acute alcohol poisoning. METHODS: Analysis of routine mortality data and of a case-control study of mortality among working-age (25-54 years) men occurring in the Russian city of Izhevsk, west of the Ural mountains, 2003-05. Interviews were carried out with proxy informants for both the dead cases (N = 1750) and the controls (N = 1750) selected at random from a population register. Mortality was analysed according to indicators of alcohol problems. RESULTS: Hazardous drinking was associated with an increased risk of death from circulatory diseases as a whole [odds ratio (OR) = 4.14, 95% confidence interval (CI) 3.23, 5.31] adjusted for age, smoking and education. The association with alcoholic cardiomyopathy was particularly strong (OR = 15.7, 95% CI 9.5, 25.9). Although there was no association with deaths from myocardial infarction (MI; OR = 1.17, 95% CI 0.59, 2.32), there was a strong association with the aggregate of all other ischaemic heart disease (IHD; OR = 4.04, 95% CI 2.79, 5.84). Stronger associations for each of these causes (other than MI) were seen with whether or not the man had drunk very heavily in the previous week. However, associations also remained when analyses were restricted to subjects with no evidence of recent heavy drinking, suggesting that misclassification of acute alcohol poisonings is unlikely to explain these overall associations. CONCLUSION: Taken as a whole, the available evidence suggests that the positive association of alcohol with increased cardiovascular disease mortality may be best explained as being the result of a combination of chronic and acute alcohol consumption resulting in alcohol-related cardiac disorders, especially cardiomyopathy, rather than being due to misclassification of acute alcohol poisoning. Further work is required to understand the mechanisms underlying the link between heavy alcohol consumption and deaths classified as being due to IHD (other than MI). PMID- 20591987 TI - HLA-DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica. AB - BACKGROUND: Association of the HLA-DRB1*1501 allele with multiple sclerosis is well established, but its association with neuromyelitis optica has only been evaluated in small populations. METHODS: We performed a case-control genetic association study to evaluate the association of HLA-DRB1*1501 with neuromyelitis optica. The single nucleotide polymorphism rs3135388, which tags HLA-DRB1*1501, was genotyped in 164 patients with neuromyelitis optica, 220 patients with multiple sclerosis and 959 controls matched for age, gender and ethnicity. Genotyping for rs3135388 was performed by Taqman-based 5' nuclease assay. RESULTS: Rs3135388*A was positively associated with multiple sclerosis (OR = 3.93; 95% CI = 2.58-5.97, p = 1.18 x 10(-09)) but negatively associated with NMO (OR = 0.57; 95% CI = 0.36-0.91, p = 0.01). CONCLUSIONS: Multiple sclerosis and neuromyelitis optica differ in their associations with DRB1*1501. PMID- 20591989 TI - It's all about change: the antigen-driven initiation of B-cell receptor signaling. AB - B-cell responses are initiated by the binding of foreign antigens to the clonally distributed B-cell receptors (BCRs) resulting in the triggering of signaling cascades that activate a variety of genes associated with B-cell activation. Although we now understand the molecular nature of the signaling pathways in considerable detail what remains only poorly understood are the mechanisms by which the information that antigen has bound to the BCR ectodomain is transduced across the B-cell membrane to the BCR cytoplasmic domains to trigger signaling. To a large part this gap in knowledge is because of the paucity of techniques to temporally and spatially resolve changes in the behavior of the BCR that occur within several seconds of antigen binding. With the advent of new live-cell imaging technologies we are gaining our first clear views of the events that lead up to the triggering of BCR signaling cascades. These events may provide potential new targets for therapeutic intervention in disease involving hyper or chronic activation of B cells. PMID- 20591988 TI - The role of the microenvironment in mammary gland development and cancer. AB - The mammary gland is composed of a diverse array of cell types that form intricate interaction networks essential for its normal development and physiologic function. Abnormalities in these interactions play an important role throughout different stages of tumorigenesis. Branching ducts and alveoli are lined by an inner layer of secretory luminal epithelial cells that produce milk during lactation and are surrounded by contractile myoepithelial cells and basement membrane. The surrounding stroma comprised of extracellular matrix and various cell types including fibroblasts, endothelial cells, and infiltrating leukocytes not only provides a scaffold for the organ, but also regulates mammary epithelial cell function via paracrine, physical, and hormonal interactions. With rare exceptions breast tumors initiate in the epithelial compartment and in their initial phases are confined to the ducts but this barrier brakes down with invasive progression because of a combination of signals emitted by tumor epithelial and various stromal cells. In this article, we overview the importance of cellular interactions and microenvironmental signals in mammary gland development and cancer. PMID- 20591990 TI - Automated quantitative live cell fluorescence microscopy. AB - Advances in microscopy automation and image analysis have given biologists the tools to attempt large scale systems-level experiments on biological systems using microscope image readout. Fluorescence microscopy has become a standard tool for assaying gene function in RNAi knockdown screens and protein localization studies in eukaryotic systems. Similar high throughput studies can be attempted in prokaryotes, though the difficulties surrounding work at the diffraction limit pose challenges, and targeting essential genes in a high throughput way can be difficult. Here we will discuss efforts to make live-cell fluorescent microscopy based experiments using genetically encoded fluorescent reporters an automated, high throughput, and quantitative endeavor amenable to systems-level experiments in bacteria. We emphasize a quantitative data reduction approach, using simulation to help develop biologically relevant cell measurements that completely characterize the cell image. We give an example of how this type of data can be directly exploited by statistical learning algorithms to discover functional pathways. PMID- 20591993 TI - The client, the clinician, and the computer. PMID- 20591991 TI - Higher-order genome organization in human disease. AB - Genomes are organized into complex higher-order structures by folding of the DNA into chromatin fibers, chromosome domains, and ultimately chromosomes. The higher order organization of genomes is functionally important for gene regulation and control of gene expression programs. Defects in how chromatin is globally organized are relevant for physiological and pathological processes. Mutations and transcriptional misregulation of several global genome organizers are linked to human diseases and global alterations in chromatin structure are emerging as key players in maintenance of genome stability, aging, and the formation of cancer translocations. PMID- 20591994 TI - State mental health policy: It's never too late to do it right: lessons from behavioral health reform in New Mexico. AB - This column describes an initiative to reform the public behavioral health system in New Mexico, which has placed publicly funded services under the management of a single for-profit private corporation. The authors discuss problems that they attribute to the state's "top-down model of planning and implementation": complex documentation requirements that increase administrative burden on providers, unrealistically high expectations for a comprehensive information technology system, inadequate monitoring that hampers assessment of reform, and insufficient attention to the rural safety net. They call on other states to better incorporate experiences of those delivering and receiving services into the design and timing of reform initiatives. PMID- 20591995 TI - Commentary: States that learn resilience need not fear reform. PMID- 20591992 TI - Cellular strategies of axonal pathfinding. AB - Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment. PMID- 20591996 TI - Law & psychiatry: Gun laws and mental illness: how sensible are the current restrictions? AB - This column describes federal and state laws to restrict access to firearms among people with mental illness. The contribution to public safety of these laws is likely to be small because only 3%-5% of violent acts are attributable to serious mental illness, and most do not involve guns. The categories of persons with mental illnesses targeted by the laws may not be at higher risk of violence than other subgroups in this population. The laws may deter people from seeking treatment for fear of losing the right to possess firearms and may reinforce stereotypes of persons with mental illnesses as dangerous. PMID- 20591997 TI - Datapoints: psychotropic drug utilization among elderly nursing home residents in the United States. PMID- 20591998 TI - Economic grand rounds: Predictors of missed appointments over the course of child mental health treatment. AB - Although missed appointments in service delivery systems reduce effective case management, clinical efficiency, staff morale, and resource utilization, researchers have paid little attention to the impact of missed appointments on patient care. This column presents findings from a study that examined predictors of missed appointments during the course of therapy among 2,903 psychiatric patients between the ages of three and 17. Self-reported history of maternal depression proved to be the most powerful predictor. Living more than 30 miles from the clinic and having a parent who was single or never married also predicted missed appointments. PMID- 20591999 TI - Best practices: Use of an administrative review committee at New Hampshire Hospital to mitigate risk with high-profile patients. AB - An increasing number of patients manifesting violent and aggressive behaviors are treated at New Hampshire Hospital. Over the past ten years, the volume of referrals on an involuntary emergency petition has increased 70%. New Hampshire Hospital has successfully initiated its Administrative Review Committee, which confers a risk management process to mitigate potential liability for the hospital and treating clinicians for these high-risk patients. This best practice is viewed as helpful by clinicians and by the hospital's legal counsel. Hospitals treating similar high-risk patients may also benefit from developing a similar committee and risk management process. PMID- 20592000 TI - An examination of premature mortality among decedents with serious mental illness and those in the general population. AB - OBJECTIVES: The primary aim of this retrospective study of death records was to determine whether there were significant differences in years of potential life lost (YPLL) between decedents with serious and persistent mental illness at a community mental health center (N=647) and decedents in the general population (N=15,517) after the analysis adjusted for sociodemographic factors and cause of death. METHODS: Clinical case management files from a community mental health center were matched to state death records from 1998 to 2004 to identify decedents being treated for a serious and persistent mental illness. Differences in leading causes of death and YPLL were calculated with descriptive and multivariate methods. RESULTS: Mean+/-SD YPLL for the decedents with serious and persistent mental illness was 14.5+/-10.6, compared with 10.3+/-6.7 for the general population. Heart disease was the leading cause of death for both groups. Mean differences in YPLL after adjustment for gender, race, marital status, and education ranged from 1.7 years for chronic lower respiratory disease to 13.1 years for accidents and were significant for every leading cause of death. Differences in cause of death did not explain the difference in YPLL. Suicide, cancer, accidents, liver disease, and septicemia were differentially associated with YPLL for persons with serious and persistent mental illness. CONCLUSIONS: Suicide, cancer, accidents, liver disease, and septicemia increased premature mortality among persons with serious and persistent mental illness. Along with ongoing suicide prevention programs, efforts to integrate primary and psychiatric care should focus on these preventable causes of early death. PMID- 20592001 TI - Psychiatric and psychological predictors of self-reported health of African Americans with severe mental illness. AB - OBJECTIVE: Persons with severe mental illness do not receive adequate general medical health care, and African Americans are at greater risk of poor-quality care than their European-American counterparts. Services for patients with mental illness should include an assessment of health status. Self-report is the most efficient means of obtaining health information but may be susceptible to bias. The purpose of the study was to determine the effects of psychiatric symptoms, psychological factors, and demographic variables on the global self-reported health of African-American psychiatric patients. METHODS: Study participants were a sample of 151 African-American psychiatric patients who received an orally administered screening interview of self-report scales, including measures of paranoia, lack of trust, need for approval, and self-esteem. Structural equation modeling (SEM) was used to estimate the effects of demographic characteristics (gender, age, and education), psychological factors (distrust, need for approval, cultural mistrust, and self-esteem), and psychiatric symptoms (subjective and objective measures of psychosis) on global self-reported health. RESULTS: The best-fitting SEM model excluded demographic variables and indicated that the latent construct for psychological factors (beta=.63) had a much stronger influence than psychiatric symptoms (beta=.37) on the self-reported health status of these patients. CONCLUSIONS: Physicians' assessments of medical complaints by patients with severe mental illness should consider the effects of nonclinical psychological factors on patients' reporting. Psychological factors associated with attitudes in the larger African-American community toward health care providers are also present in the segment with severe mental illness. PMID- 20592002 TI - Who terminates from ACT and why? Data from the National VA Mental Health Intensive Case Management Program. AB - OBJECTIVE: One of the original principles of assertive community treatment (ACT) is that treatment should be time unlimited. Although termination is not uncommon in ACT, it has not been empirically studied. This study examined termination from a large program based on ACT. METHODS: This study used national data from the Department of Veterans Affairs Mental Health Intensive Case Management program modeled on ACT to compare veteran characteristics, patterns of service delivery, and early clinical changes among veterans who terminated early (less than one year) and later (one to three years) with those of veterans had not terminated after three years. Bivariate comparisons and multinomial logistic regression analyses were used to identify factors associated with early and later termination. RESULTS: Among 1,402 veterans enrolled in fiscal years (FY) 2002 2004, 16% terminated early, 26% terminated later, and 57% had not terminated after three years. Compared with those who had not terminated, those who terminated early showed higher suicidality scores, and participants who terminated early and those who terminated later were less likely to have a diagnosis of schizophrenia and were more likely to have lower quality of life at entry. Stronger differentiating effects were observed for program participation. Those who terminated received less intensive services during the first six months of participation and had a weaker therapeutic alliance. Although participants who terminated early showed more violent behavior at follow-up than the other two groups, there were no other differences in early clinical changes. CONCLUSIONS: Rates of both early and later termination were substantial, and less active participation was a stronger predictor of termination than either patient characteristics or clinical changes. A diagnosis of schizophrenia was associated with continued treatment. Further research is needed to determine the impact of termination on longer-term outcomes. PMID- 20592003 TI - Predictors of early dropout from psychotherapy for depression in community practice. AB - OBJECTIVE: Data from a managed care health system were used to examine demographic, clinical, and health system predictors of early dropout from psychotherapy for depression. METHODS: A total of 238 members of a mixed-model health plan calling to request an initial psychotherapy visit for depression completed a brief survey regarding depression severity, perceived need for treatment, and expected benefit. Claims records were used to assess therapy visits attended over the following 90 days. RESULTS: Dropout rates before the first therapy visit were somewhat higher among women (p=.041) and younger members (p=.017), moderately higher among those with lower depression severity (p=.012), and markedly higher among callers referred to network-model psychotherapists (compared with those given appointments with group-model therapists at health plan clinics) (p<.001). By the second visit, however, cumulative dropout rates were similar for group- and network-model therapists. The only significant predictors of cumulative dropout rates before the second visit were less severe depression at the screening call (p=.004) and lower self-rated importance of initiating psychotherapy (p=.046). CONCLUSIONS: Early dropout from psychotherapy for depression was only weakly related to consumers' demographic characteristics. Dropout rates were lower among those with more severe depression, but a significant number of persons with moderate or severe symptoms of depression still discontinued treatment before the second visit. Allocation of visits for individual consumers was markedly different for group- and network-model psychotherapists, but these data did not allow for examination of differences in outcomes for those two treatment models. PMID- 20592004 TI - Ethnic differences and similarities in outpatient treatment for depression in the Netherlands. AB - OBJECTIVE: There are widespread concerns about disparities in mental health treatment for ethnic minority groups. However, previous research in this area has been limited mainly to the United States and Great Britain, raising doubts about the external validity with respect to other European countries. This study addressed ethnic differences in characteristics of outpatient treatment for depression in the Netherlands. METHODS: Longitudinal data (2001-2005) were extracted from a nationwide psychiatric case register. The sample consisted of 17,270 episodes of outpatient depression care. Information was available about timeliness of the initial treatment contact, treatment intensity, dropout, and early reregistration for mental health care. Data were analyzed with linear, logistic, and Cox regression analyses. RESULTS: When analyses were controlled for illness and demographic characteristics, timeliness and treatment intensity were somewhat less favorable for Moroccan, Turkish, and other non-Western clients compared with ethnic Dutch. No significant differences were found between minority and ethnic Dutch groups in dropout and early reregistration. Some treatment characteristics were in fact more favorable for Surinamese and Antillean clients compared with ethnic Dutch. CONCLUSIONS: The data provided insufficient support for the idea that treatment characteristics are generally less favorable for clients from ethnic minority groups. This finding may be related to the promotion of culturally sensitive approaches to care in mainstream mental health services but may also indicate that the role of traditional barriers, like stigma and taboo, is smaller than is usually suggested. However, the influence of language proficiency, which is notably better among Surinamese and Dutch Antillean compared with Turkish and Moroccan clients, should not be disregarded. PMID- 20592005 TI - Associations of housing status with substance abuse treatment and service use outcomes among veterans. AB - OBJECTIVE: This secondary analysis evaluated the prevalence and stability of homelessness over one year among veterans entering substance abuse treatment and explored associations among housing status, treatment outcomes, and Veterans Affairs (VA) service utilization. METHODS: Participants in a trial of on-site primary care for veterans entering substance abuse treatment (N=622) were placed in four groups based on housing status: housed at baseline and final follow-up (41%), homeless at baseline and final follow-up (27%), housed at baseline but homeless at final follow-up (8%), and homeless at baseline but housed at final follow-up (24%). Groups were compared on treatment retention, changes in Addiction Severity Index (ASI) composite scores, and VA service utilization and costs. RESULTS: Treatment retention and changes in ASI alcohol composites did not differ between groups. Compared with scores in the consistently housed group, the ASI drug composites improved less over time in the consistently homeless group (p=.031) and the ASI psychiatric composites improved less in the group housed at baseline and homeless at final follow-up (p=.019). All homeless groups were more likely than the consistently housed group to have inpatient admissions and incurred higher total treatment costs. The consistently homeless group was more likely to use emergency care than the consistently housed group. CONCLUSIONS: Homelessness affects substance abuse treatment outcomes and costs. Interventions are needed to reduce homelessness among veterans entering substance abuse treatment. PMID- 20592007 TI - Comprehensive electronic decision support systems. AB - This Open Forum describes a vision of comprehensive electronic decision support systems that could provide information and supports to both clients and clinicians in order to facilitate shared decision making and encourage collaborative management of illness and wellness. The authors argue that these systems have the potential to improve mental health care by enhancing and connecting the three elements of evidence-based medicine: client preferences, research evidence, and clinician skills. PMID- 20592006 TI - Advisor-Teller Money Manager (ATM) therapy for substance use disorders. AB - OBJECTIVE: Patients with concomitant psychiatric and substance use disorders are commonly assigned representative payees or case managers to help manage their funds, but money management has not been conceptualized as a theory-based treatment. This randomized clinical trial was conducted to determine the effect of a money management-based therapy, advisor-teller money manager (ATM), on substance abuse or dependence. METHODS: Ninety patients at a community mental health center who had a history of cocaine or alcohol abuse or dependence were assessed after random assignment to 36 weeks of ATM (N=47) or a control condition in which use of a financial workbook was reviewed (N=43). Patients assigned to ATM were encouraged to deposit their funds into a third-party account, plan weekly expenditures, and negotiate monthly budgets. Substance use calendars and urine toxicology tests were collected every other week for 36 weeks and again 52 weeks after randomization. RESULTS: Patients assigned to ATM had significantly more negative toxicologies for cocaine metabolite over time than patients in the control group, and treating clinicians rated ATM patients as significantly more likely to be abstinent from illicit drugs. Self-reported abstinence from alcohol did not significantly differ between groups. Unexpectedly, patients assigned to ATM were more likely to be assigned a representative payee or a conservator than control participants during the follow-up period (ten of 47 versus two of 43). One patient in ATM assaulted the therapist when his check had not arrived. CONCLUSIONS: ATM is an efficacious therapy for the treatment of cocaine abuse or dependence among people with concomitant psychiatric illness but requires protection of patient autonomy and staff safety. PMID- 20592008 TI - Social class and work functioning in treatment for depression. AB - OBJECTIVE: This study examined work functioning across three treatments for depression in relation to social class. METHODS: The study was based on data available from the National Institute of Mental Health Treatment of Depression Collaborative Research Program (1982 to 1986). Participants included 239 patients with major depressive disorder. Primary measures included the work functioning domain on the Social Adjustment Scale, the Hollingshead Two-Factor Index of Social Position, and family income. Analyses used hierarchical linear modeling to test the association of social class with work functioning over the course of treatment. RESULTS: Social class was positively associated with improvement in work functioning across all three treatments for depression. CONCLUSIONS: These findings suggest that there may be limitations in the use of empirically supported treatments with depressed patients from a lower social class, because their improvement rates in work functioning were less than those of middle-class persons with depression, even though they were treated with the same modalities. PMID- 20592009 TI - Racial preferences for participation in a depression prevention trial involving problem-solving therapy. AB - OBJECTIVES: This study compared African Americans' and Caucasians' willingness to participate in an indicated intervention to prevent depression with problem solving therapy. It also examined participants' problem-solving skills. Hypotheses stated that there would be no racial differences in consent rates and that social problem-solving coping skills would be lower among African Americans than Caucasians. METHODS: Proportions of African Americans and Caucasians who consented were compared, as were Social Problem Solving Inventory scores between the groups. RESULTS: Of 2,788 individuals approached, 82 (4%) of 1,970 Caucasians and 46 (6%) of 818 African Americans signed consent, and the difference was not significant (p=.09). Racial differences were observed in neither Social Problem Solving Inventory scores nor in the relationship between problem-solving skills and depressive symptoms. CONCLUSIONS: African Americans with depression demonstrated a willingness to participate in an indicated trial of depression prevention. Furthermore, both groups would appear to benefit from the problem solving process. PMID- 20592010 TI - End-of-life care for veterans with schizophrenia and cancer. AB - OBJECTIVE: This study compared the quality of end-of-life care between veterans with and without schizophrenia who died of cancer in the northwestern United States. METHODS: In this cross-sectional study, medical records of 60 veterans with schizophrenia and 196 with no major mental illness who died of cancer were compared on hospice enrollment, palliative and life-sustaining interventions, advance directives, and site of death. RESULTS: Among veterans with schizophrenia, 58% had an advance directive, 73% received an opiate before hospice enrollment, 63% had a physician order to forgo cardiopulmonary resuscitation, 55% were hospice enrolled, and 27% died in the hospital. Schizophrenia patients had longer hospice stays (107+/-144 versus 63+/-96 days, p=.05) and more physician orders for life-sustaining treatment (15% versus 5%, p=.006) compared with veterans without mental illness. CONCLUSIONS: On most measures, veterans with schizophrenia who died of cancer received comparable or better end-of-life care than veterans without mental illness. PMID- 20592011 TI - The need for patient education at a psychiatric clinic in Nigeria. PMID- 20592012 TI - Provider communication in split treatment: a survey. PMID- 20592013 TI - A seven-gene set associated with chronic hypoxia of prognostic importance in hepatocellular carcinoma. AB - PURPOSE: Hepatocellular carcinomas (HCC) have an unpredictable clinical course, and molecular classification could provide better insights into prognosis and patient-directed therapy. We hypothesized that in HCC, certain microenvironmental regions exist with a characteristic gene expression related to chronic hypoxia which would induce aggressive behavior. EXPERIMENTAL DESIGN: We determined the gene expression pattern for human HepG2 liver cells under chronic hypoxia by microarray analysis. Differentially expressed genes were selected and their clinical values were assessed. In our hypothesis-driven analysis, we included available independent microarray studies of patients with HCC in one single analysis. Three microarray studies encompassing 272 patients were used as training sets to determine a minimal prognostic gene set, and one recent study of 91 patients was used for validation. RESULTS: Using computational methods, we identified seven genes (out of 3,592 differentially expressed under chronic hypoxia) that showed correlation with poor prognostic indicators in all three training sets (65/139/73 patients) and this was validated in a fourth data set (91 patients). Retrospectively, the seven-gene set was associated with poor survival (hazard ratio, 1.39; P = 0.007) and early recurrence (hazard ratio, 2.92; P = 0.007) in 135 patients. Moreover, using a hypoxia score based on this seven-gene set, we found that patients with a score of >0.35 (n = 42) had a median survival of 307 days, whereas patients with a score of < or =0.35 (n = 93) had a median survival of 1,602 days (P = 0.005). CONCLUSIONS: We identified a unique, liver-specific, seven-gene signature associated with chronic hypoxia that correlates with poor prognosis in HCCs. PMID- 20592014 TI - Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma. AB - PURPOSE: Paragangliomas of the head and neck are neuroendocrine tumors and are associated with germ line mutations of the tricarboxylic acid cycle-related genes SDHB, SDHC, SDHD, and SDHAF2. Hypoxia is important in most solid tumors, and was directly implicated in tumorigenesis over 40 years ago when it was shown that dwelling at high altitudes increases the incidence of carotid body hyperplasia and paragangliomas. Although recent research has now elucidated several pathways of hypoxia in paragangliomas, nothing is currently known of the genetics or of gene-environment interactions in high-altitude paraganglioma. We postulated that SDH mutations might play a role in these tumors. EXPERIMENTAL DESIGN: Patients from a Mexican family, originating and resident in Guadalajara, were tested for mutations of SDHD, and subsequently, for mutations of SDHB followed by immunohistochemical confirmation of SDHB loss. RESULTS: Two patients, born and resident at altitudes of between 1,560 and 2,240 m, were found to have head and neck paragangliomas, including a remarkably aggressive recurrent tumor. Mutation analysis identified a pathogenic missense mutation in exon 7 of SDHB, c.689G>A, p.Arg230His, and loss of the SDHB protein was confirmed by immunohistochemistry. CONCLUSIONS: This is the first report of a SDH gene mutation in paraganglioma at high altitude. A rapidly recurrent head and neck paraganglioma is a very rare finding in an SDH mutation carrier, suggesting a gene-environment interaction. Neither patient showed evidence of sympathetic paraganglioma. PMID- 20592015 TI - Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR. AB - PURPOSE: Aberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan. EXPERIMENTAL DESIGN: In a small evaluation cohort, four gene promoters (DCC, Kif1a, NISCH, and Rarb) were found to be methylated with increased frequency in samples from cancer patients specifically. We then examined DNA from 93 plasma samples from patients with abnormal findings in the lung detected upon CT scan for aberrant methylation of these four gene promoters by quantitative fluorogenic real-time PCR. The patients were divided into two groups, ground glass opacity (n = 23) and cancerous tumors (n = 70). Plasma DNA from age-matched nodule-free individuals were used as controls (n = 80). RESULTS: In plasma, 73% of patients with cancerous tumors showed methylation of at least one gene with a specificity of 71% (P = 0.0001). Only 22% patients with ground glass opacity exhibited methylation of at least one gene. When smoking history was taken into account, 72% of cancer patients with no smoking history or those who smoked <20 pack-years showed methylation of at least one gene with 100% specificity (P = 0.05) when compared with matched controls. Among heavy smokers with 20+ pack years of smoking history, 30% of the control group and 73% of the patients with cancerous tumors showed methylation (P = 0.0001). CONCLUSIONS: These biomarkers can distinguish between cancerous and noncancerous abnormal CT findings. PMID- 20592016 TI - BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. AB - PURPOSE: A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The present analysis was aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in PCa patients. EXPERIMENTAL DESIGN: To map molecular progression in PCa outgrowth, we used fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood. RESULTS: We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (P < 0.05), invasion to pelvic lymph nodes (P < 0.05), as well as biochemical recurrence (P < 0.01). Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites. In four of seven patients with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs. CONCLUSIONS: Small subpopulations of PCa cells bearing BRCA1 losses might be one confounding factor initiating tumor dissemination and might provide an early indicator of shortened disease-free survival. PMID- 20592017 TI - MDM2 mediates ubiquitination and degradation of activating transcription factor 3. AB - Activating transcription factor 3 (ATF3) is a common stress sensor, and its rapid induction by cellular stresses (e.g. DNA damage) is crucial for cells to mount appropriate responses (e.g. activating the tumor suppressor p53) and maintain homeostasis. Although emerging evidence suggests that dysregulation of ATF3 contributes to occurrences of human diseases including cancer, the mechanism(s) by which ATF3 expression is regulated is largely unknown. Here, we demonstrate that mouse double minute 2 (MDM2) is a bona fide E3 ubiquitin ligase for ATF3 and regulates ATF3 expression by promoting its degradation. MDM2 via its C-terminal RING finger can bind to the Basic region of ATF3 and mediate the addition of ubiquitin moieties to the ATF3 leucine zipper domain. As a consequence, ATF3, but not a mutant deficient in MDM2 binding (Delta80-100), is degraded by MDM2 mediated proteolysis. Consistent with these results, ablation of MDM2 in cells not only increases basal ATF3 levels, but results in stabilization of ATF3 in late stages of DNA damage responses. Because ATF3 was recently identified as a p53 activator, these results suggest that MDM2 could inactivate p53 through an additional feedback mechanism involving ATF3. Therefore, we provide the first evidence demonstrating that ATF3 is regulated by a posttranslational mechanism. PMID- 20592018 TI - D1 and D2 dopamine receptor-mediated inhibition of activated normal T cell proliferation is lost in jurkat T leukemic cells. AB - Dopamine is a catecholamine neurotransmitter, which plays an important role in the regulation of T cell functions. In activated T cells from normal volunteers, stimulation of D(1) and D(2) dopamine receptors inhibit cell proliferation and cytokine secretion. However, there is no report yet regarding the regulatory role of D(1) and D(2) dopamine receptors in abnormally proliferating T cells. The present study investigates the expression and effect of activation of these dopamine receptors in Jurkat cells, a leukemic T cell line showing uncontrolled proliferation. Like normal human T cells, in Jurkat cells, D(1) and D(2) dopamine receptors are also expressed; however, unlike activated normal T cells, stimulation of these dopamine receptors in Jurkat cells fails to inhibit their T cell receptor-induced proliferation. This alteration is due to failure of D(1) dopamine receptor-mediated activation of cyclic AMP signaling and a missense mutation at the third cytoplasmic loop of D(2) dopamine receptors affecting inhibition of phosphorylation of ZAP-70, an important downstream protein transducing signal from the T cell receptor. These results help to understand the biology of abnormal proliferation of T cells in pathophysiological conditions where dopamine plays an important role. PMID- 20592019 TI - MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA. AB - Lipopolysaccharide (LPS) activates the innate immune response through the Toll like receptor 4 (TLR4).MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IV(A) in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IV(A) species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IV(A). Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IV(A), effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IV(A). Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A). PMID- 20592020 TI - C-terminal peptides of tissue factor pathway inhibitor are novel host defense molecules. AB - Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C terminus, also modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classic" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GGLIKTKRKRKKQRVKIAYEEIFVKNM (GGL27), was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classic pathway of complement activation. Furthermore, GGL27 displayed anti endotoxic effects in vitro and in vivo in a mouse model of LPS shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections. PMID- 20592021 TI - Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex. AB - C1, the complex that triggers the classic pathway of complement, is a 790-kDa assembly resulting from association of a recognition protein C1q with a Ca(2+) dependent tetramer comprising two copies of the proteases C1r and C1s. Early structural investigations have shown that the extended C1s-C1r-C1r-C1s tetramer folds into a compact conformation in C1. Recent site-directed mutagenesis studies have identified the C1q-binding sites in C1r and C1s and led to a three dimensional model of the C1 complex (Bally, I., Rossi, V., Lunardi, T., Thielens, N. M., Gaboriaud, C., and Arlaud, G. J. (2009) J. Biol. Chem. 284, 19340-19348). In this study, we have used a mass spectrometry-based strategy involving a label free semi-quantitative analysis of protein samples to gain new structural insights into C1 assembly. Using a stable chemical modification, we have compared the accessibility of the lysine residues in the isolated tetramer and in C1. The labeling data account for 51 of the 73 lysine residues of C1r and C1s. They strongly support the hypothesis that both C1s CUB(1)-EGF-CUB(2) interaction domains, which are distant in the free tetramer, associate with each other in the C1 complex. This analysis also provides the first experimental evidence that, in the proenzyme form of C1, the C1s serine protease domain is partly positioned inside the C1q cone and yields precise information about its orientation in the complex. These results provide further structural insights into the architecture of the C1 complex, allowing significant improvement of our current C1 model. PMID- 20592022 TI - Structural analysis of Saccharomyces cerevisiae alpha-galactosidase and its complexes with natural substrates reveals new insights into substrate specificity of GH27 glycosidases. AB - Alpha-galactosidases catalyze the hydrolysis of terminal alpha-1,6-galactosyl units from galacto-oligosaccharides and polymeric galactomannans. The crystal structures of tetrameric Saccharomyces cerevisiae alpha-galactosidase and its complexes with the substrates melibiose and raffinose have been determined to 1.95, 2.40, and 2.70 A resolution. The monomer folds into a catalytic (alpha/beta)(8) barrel and a C-terminal beta-sandwich domain with unassigned function. This pattern is conserved with other family 27 glycosidases, but this enzyme presents a unique 45-residue insertion in the beta-sandwich domain that folds over the barrel protecting it from the solvent and likely explaining its high stability. The structure of the complexes and the mutational analysis show that oligomerization is a key factor in substrate binding, as the substrates are located in a deep cavity making direct interactions with the adjacent subunit. Furthermore, docking analysis suggests that the supplementary domain could be involved in binding sugar units distal from the scissile bond, therefore ascribing a role in fine-tuning substrate specificity to this domain. It may also have a role in promoting association with the polymeric substrate because of the ordered arrangement that the four domains present in one face of the tetramer. Our analysis extends to other family 27 glycosidases, where some traits regarding specificity and oligomerization can be formulated on the basis of their sequence and the structures available. These results improve our knowledge on the activity of this important family of enzymes and give a deeper insight into the structural features that rule modularity and protein-carbohydrate interactions. PMID- 20592023 TI - Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function. AB - The paired box homeodomain Pax6 is crucial for endocrine cell development and function and plays an essential role in glucose homeostasis. Indeed, mutations of Pax6 are associated with diabetic phenotype. Importantly, homozygous mutant mice for Pax6 are characterized by markedly decreased beta and delta cells and absent alpha cells. To better understand the critical role that Pax6 exerts in glucagon producing cells, we developed a model of primary rat alpha cells. To study the transcriptional network of Pax6 in adult and differentiated alpha cells, we generated Pax6-deficient primary rat alpha cells and glucagon-producing cells, using either specific siRNA or cells expressing constitutively a dominant negative form of Pax6. In primary rat alpha cells, we confirm that Pax6 controls the transcription of the Proglucagon and processing enzyme PC2 genes and identify three new target genes coding for MafB, cMaf, and NeuroD1/Beta2, which are all critical for Glucagon gene transcription and alpha cell differentiation. Furthermore, we demonstrate that Pax6 directly binds and activates the promoter region of the three genes through specific binding sites and that constitutive expression of a dominant-negative form of Pax6 in glucagon-producing cells (InR1G9) inhibits the activities of the promoters. Finally our results suggest that the critical role of Pax6 action on alpha cell differentiation is independent of those of Arx and Foxa2, two transcription factors that are necessary for alpha cell development. We conclude that Pax6 is critical for alpha cell function and differentiation through the transcriptional control of key genes involved in glucagon gene transcription, proglucagon processing, and alpha cell differentiation. PMID- 20592024 TI - Analysis of spliceosomal proteins in Trypanosomatids reveals novel functions in mRNA processing. AB - In trypanosomatids, all mRNAs are processed via trans-splicing, although cis splicing also occurs. In trans-splicing, a common small exon, the spliced leader (SL), which is derived from a small SL RNA species, is added to all mRNAs. Sm and Lsm proteins are core proteins that bind to U snRNAs and are essential for both these splicing processes. In this study, SmD3- and Lsm3-associated complexes were purified to homogeneity from Leishmania tarentolae. The purified complexes were analyzed by mass spectrometry, and 54 and 39 proteins were purified from SmD3 and Lsm complexes, respectively. Interestingly, among the proteins purified from Lsm3, no mRNA degradation factors were detected, as in Lsm complexes from other eukaryotes. The U1A complex was purified and mass spectrometry analysis identified, in addition to U1 small nuclear ribonucleoprotein (snRNP) proteins, additional co-purified proteins, including the polyadenylation factor CPSF73. Defects observed in cells silenced for U1 snRNP proteins suggest that the U1 snRNP functions exclusively in cis-splicing, although U1A also participates in polyadenylation and affects trans-splicing. The study characterized several trypanosome-specific nuclear factors involved in snRNP biogenesis, whose function was elucidated in Trypanosoma brucei. Conserved factors, such as PRP19, which functions at the heart of every cis-spliceosome, also affect SL RNA modification; GEMIN2, a protein associated with SMN (survival of motor neurons) and implicated in selective association of U snRNA with core Sm proteins in trypanosomes, is a master regulator of snRNP assembly. This study demonstrates the existence of trypanosomatid-specific splicing factors but also that conserved snRNP proteins possess trypanosome-specific functions. PMID- 20592025 TI - Two atypical L-cysteine-regulated NADPH-dependent oxidoreductases involved in redox maintenance, L-cystine and iron reduction, and metronidazole activation in the enteric protozoan Entamoeba histolytica. AB - We discovered novel catalytic activities of two atypical NADPH-dependent oxidoreductases (EhNO1/2) from the enteric protozoan parasite Entamoeba histolytica. EhNO1/2 were previously annotated as the small subunit of glutamate synthase (glutamine:2-oxoglutarate amidotransferase) based on similarity to authentic bacterial homologs. As E. histolytica lacks the large subunit of glutamate synthase, EhNO1/2 were presumed to play an unknown role other than glutamine/glutamate conversion. Transcriptomic and quantitative reverse PCR analyses revealed that supplementation or deprivation of extracellular L-cysteine caused dramatic up- or down-regulation, respectively, of EhNO2, but not EhNO1 expression. Biochemical analysis showed that these FAD- and 2[4Fe-4S]-containing enzymes do not act as glutamate synthases, a conclusion which was supported by phylogenetic analyses. Rather, they catalyze the NADPH-dependent reduction of oxygen to hydrogen peroxide and L-cystine to L-cysteine and also function as ferric and ferredoxin-NADP(+) reductases. EhNO1/2 showed notable differences in substrate specificity and catalytic efficiency; EhNO1 had lower K(m) and higher k(cat)/K(m) values for ferric ion and ferredoxin than EhNO2, whereas EhNO2 preferred L-cystine as a substrate. In accordance with these properties, only EhNO1 was observed to physically interact with intrinsic ferredoxin. Interestingly, EhNO1/2 also reduced metronidazole, and E. histolytica transformants overexpressing either of these proteins were more sensitive to metronidazole, suggesting that EhNO1/2 are targets of this anti-amebic drug. To date, this is the first report to demonstrate that small subunit-like proteins of glutamate synthase could play an important role in redox maintenance, L cysteine/L-cystine homeostasis, iron reduction, and the activation of metronidazole. PMID- 20592026 TI - Antigenic Variation among Bordetella: Bordetella bronchiseptica strain MO149 expresses a novel o chain that is poorly immunogenic. AB - The O chain polysaccharide (O PS) of Bordetella bronchiseptica and Bordetella parapertussis lipopolysaccharide is a homopolymer of 2,3-diacetamido-2,3 dideoxygalacturonic acid (GalNAc3NAcA) in which some of the sugars are present as uronamides. The terminal residue contains several unusual modifications. To date, two types of modification have been characterized, and a survey of numerous strains demonstrated that each contained one of these two modification types. Host antibody responses against the O PS are directed against the terminal residue modifications, and there is little cross-reactivity between the two types. This suggests that Bordetella O PS modifications represent a means of antigenic variation. Here we report the characterization of the O PS of B. bronchiseptica strain MO149. It consists of a novel two-sugar repeating unit and a novel terminal residue modification, with the structure Me-4-alpha-L GalNAc3NAcA-(4-beta-D-GlcNAc3NAcA-4-alpha-L-GalNAc3NAcA-)(5-6)-, which we propose be defined as the B. bronchiseptica O3 PS. We show that the O3 PS is very poorly immunogenic and that the MO149 strain contains a novel wbm (O PS biosynthesis) locus. Thus, there is greater diversity among Bordetella O PSs than previously recognized, which is likely to be a result of selection pressure from host immunity. We also determine experimentally, for the first time, the absolute configuration of the diacetimido-uronic acid sugars in Bordetella O PS. PMID- 20592027 TI - Autophagy facilitates IFN-gamma-induced Jak2-STAT1 activation and cellular inflammation. AB - Autophagy is regulated for IFN-gamma-mediated antimicrobial efficacy; however, its molecular effects for IFN-gamma signaling are largely unknown. Here, we show that autophagy facilitates IFN-gamma-activated Jak2-STAT1. IFN-gamma induces autophagy in wild-type but not in autophagy protein 5 (Atg5(-/-))-deficient mouse embryonic fibroblasts (MEFs), and, autophagy-dependently, IFN-gamma induces IFN regulatory factor 1 and cellular inflammatory responses. Pharmacologically inhibiting autophagy using 3-methyladenine, a known inhibitor of class III phosphatidylinositol 3-kinase, confirms these effects. Either Atg5(-/-) or Atg7( /-) MEFs are, independent of changes in IFN-gamma receptor expression, resistant to IFN-gamma-activated Jak2-STAT1, which suggests that autophagy is important for IFN-gamma signal transduction. Lentivirus-based short hairpin RNA for Atg5 knockdown confirmed the importance of autophagy for IFN-gamma-activated STAT1. Without autophagy, reactive oxygen species increase and cause SHP2 (Src homology 2 domain-containing phosphatase 2)-regulated STAT1 inactivation. Inhibiting SHP2 reversed both cellular inflammation and the IFN-gamma-induced activation of STAT1 in Atg5(-/-) MEFs. Our study provides evidence that there is a link between autophagy and both IFN-gamma signaling and cellular inflammation and that autophagy, because it inhibits the expression of reactive oxygen species and SHP2, is pivotal for Jak2-STAT1 activation. PMID- 20592028 TI - Ancient cytokines, the role of astakines as hematopoietic growth factors. AB - Hematopoiesis is the process by which hemocytes mature and subsequently enter the circulation. Vertebrate prokineticins (PKs) are known to take part in this process, as are the invertebrate prokineticin domain proteins, astakines. In Pacifastacus leniusculus, astakine 1 is essential for the release of new hemocytes into the open circulatory system of these animals. In addition to astakine 1, we have now cloned a homologue of astakine 1 with an insert of 13 amino acids, named as astakine 2. Both crustacean astakines lack the N-terminal AVIT motif, which is present in vertebrate PKs, and hence receptor binding differs from that of vertebrate PKs. We have found astakine-like sequences in 19 different invertebrate species, and the sequences show that some motifs are conserved among invertebrate groups. Previously we showed that astakine 1 is directly involved in hematopoiesis, and now we show that astakine 1 and astakine 2 have different roles in hemocyte lineage differentiation. Astakine 1 can stimulate proliferation of hematopoietic tissue (Hpt) cells (precursor of hemocytes) as well as specifically induce differentiation of Hpt cells along the semigranular cell lineage, whereas astakine 2 plays a role in granular cell differentiation. Moreover, we discuss the impact of the putative structures of different astakines in comparison with the vertebrate prokineticins. PMID- 20592029 TI - Peroxisome proliferator-activated receptor {delta} activators induce IL-8 expression in nonstimulated endothelial cells in a transcriptional and posttranscriptional manner. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are implicated in the regulation of lipid and glucose homeostasis. PPAR agonists have been shown to control inflammatory processes, in part by inhibiting distinct proinflammatory genes (e.g. Il-1beta and IFN-gamma). IL-8 is a member of the proinflammatory chemokine family that is important for various functions, such as mediating the adhesion of eosinophilic granulocytes onto endothelial cells. The influence of PPARdelta activators on the expression of IL-8 in noninduced quiescent endothelial cells is unclear. Therefore, we explored the influence of PPARdelta activators on the expression of IL-8 in nonstimulated endothelial cells. PPARdelta agonists induce IL-8 expression in human umbilical vein endothelial cells. This induction is demonstrated at the level of both protein and mRNA expression. Transcriptional activation studies using IL-8 reporter gene constructs and DNA binding assays revealed that PPARdelta agonists mediated their effects via an NFkappaB binding site. It is well known that IL-8 is also regulated by mRNA stability. To provide further evidence for this concept, we performed mRNA stability assays and found that PPARdelta agonists induce the mRNA stability of IL-8. In addition, we showed that PPARdelta agonists induce the phosphorylation of ERK1/2 and p38, which are known to be involved in the increase of mRNA stability. The inhibition of these MAPK signaling pathways resulted in a significant suppression of the induced IL-8 expression and the reduced mRNA stability. Therefore, our data provide the first evidence that PPARdelta induces IL-8 expression in nonstimulated endothelial cells via transcriptional as well as posttranscriptional mechanisms. PMID- 20592030 TI - p47phox molecular activation for assembly of the neutrophil NADPH oxidase complex. AB - The p47(phox) cytosolic factor from neutrophilic NADPH oxidase has always been resistant to crystallogenesis trials due to its modular organization leading to relative flexibility. Hydrogen/deuterium exchange coupled to mass spectrometry was used to obtain structural information on the conformational mechanism that underlies p47(phox) activation. We confirmed a relative opening of the protein with exposure of the SH3 Src loops that are known to bind p22(phox) upon activation. A new surface was shown to be unmasked after activation, representing a potential autoinhibitory surface that may block the interaction of the PX domain with the membrane in the resting state. Within this surface, we identified 2 residues involved in the interaction with the PX domain. The double mutant R162A/D166A showed a higher affinity for specific phospholipids but none for the C-terminal part of p22(phox), reflecting an intermediate conformation between the autoinhibited and activated forms. PMID- 20592031 TI - Exploiting antigenic diversity for vaccine design: the chlamydia ArtJ paradigm. AB - We present an interdisciplinary approach that, by incorporating a range of experimental and computational techniques, allows the identification and characterization of functional/immunogenic domains. This approach has been applied to ArtJ, an arginine-binding protein whose orthologs in Chlamydiae trachomatis (CT ArtJ) and pneumoniae (CPn ArtJ) are shown to have different immunogenic properties despite a high sequence similarity (60% identity). We have solved the crystallographic structures of CT ArtJ and CPn ArtJ, which are found to display a type II transporter fold organized in two alpha-beta domains with the arginine-binding region at their interface. Although ArtJ is considered to belong to the periplasm, we found that both domains contain regions exposed on the bacterial surface. Moreover, we show that recombinant ArtJ binds to epithelial cells in vitro, suggesting a role for ArtJ in host-cell adhesion during Chlamydia infection. Experimental epitope mapping and computational analysis of physicochemical determinants of antibody recognition revealed that immunogenic epitopes reside mainly in the terminal (D1) domain of both CPn and CT ArtJ, whereas the surface properties of the respective binding-prone regions appear sufficiently different to assume divergent immunogenic behavior. Neutralization assays revealed that sera raised against CPn ArtJ D1 partially reduce both CPn and CT infectivity in vitro, suggesting that functional antibodies directed against this domain may potentially impair chlamydial infectivity. These findings suggest that the approach presented here, combining functional and structure-based analyses of evolutionary-related antigens can be a valuable tool for the identification of cross-species immunogenic epitopes for vaccine development. PMID- 20592032 TI - X-ray crystal structures of monomeric and dimeric peptide inhibitors in complex with the human neonatal Fc receptor, FcRn. AB - The neonatal Fc receptor, FcRn, is responsible for the long half-life of IgG molecules in vivo and is a potential therapeutic target for the treatment of autoimmune diseases. A family of peptides comprising the consensus motif GHFGGXY, where X is preferably a hydrophobic amino acid, was shown previously to inhibit the human IgG:human FcRn protein-protein interaction (Mezo, A. R., McDonnell, K. A., Tan Hehir, C. A., Low, S. C., Palombella, V. J., Stattel, J. M., Kamphaus, G. D., Fraley, C., Zhang, Y., Dumont, J. A., and Bitonti, A. J. (2008) Proc. Natl. Acad. Sci. U.S.A., 105, 2337-2342). Herein, the x-ray crystal structure of a representative monomeric peptide in complex with human FcRn was solved to 2.6 A resolution. The structure shows that the peptide binds to human FcRn at the same general binding site as does the Fc domain of IgG. The data correlate well with structure-activity relationship data relating to how the peptide family binds to human FcRn. In addition, the x-ray crystal structure of a representative dimeric peptide in complex with human FcRn shows how the bivalent ligand can bridge two FcRn molecules, which may be relevant to the mechanism by which the dimeric peptides inhibit FcRn and increase IgG catabolism in vivo. Modeling of the peptide:FcRn structure as compared with available structural data on Fc and FcRn suggest that the His-6 and Phe-7 (peptide) partially mimic the interaction of His 310 and Ile-253 (Fc) in binding to FcRn, but using a different backbone topology. PMID- 20592033 TI - Human serum mannose-binding lectin senses wall teichoic acid Glycopolymer of Staphylococcus aureus, which is restricted in infancy. AB - Innate immunity is the first line of host defense against invading pathogens, and it is recognized by a variety of pattern recognition molecules, including mannose binding lectin (MBL). MBL binds to mannose and N-acetylglucosamine residues present on the glycopolymers of microorganisms. Human serum MBL functions as an opsonin and activates the lectin complement pathway. However, which glycopolymer of microorganism is recognized by MBL is still uncertain. Here, we show that wall teichoic acid of Staphylococcus aureus, a bacterial cell surface glycopolymer containing N-acetylglucosamine residue, is a functional ligand of MBL. Whereas serum MBL in adults did not bind to wall teichoic acid because of an inhibitory effect of anti-wall teichoic acid antibodies, MBL in infants who had not yet fully developed their adaptive immunity could bind to S. aureus wall teichoic acid and then induced complement C4 deposition. Our data explain the molecular reasons of why MBL-deficient infants are susceptible to S. aureus infection. PMID- 20592034 TI - Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice. AB - L3MBTL1, a paralogue of Drosophila tumor suppressor lethal(3)malignant brain tumor (l(3)mbt), binds histones in a methylation state-dependent manner and contributes to higher order chromatin structure and transcriptional repression. It is the founding member of a family of MBT domain-containing proteins that has three members in Drosophila and nine in mice and humans. Knockdown experiments in cell lines suggested that L3MBTL1 has non-redundant roles in the suppression of oncogene expression. We generated a mutant mouse strain that lacks exons 13-20 of L3mbtl1. Markedly reduced levels of a mutant mRNA with an out-of-frame fusion of exons 12 and 21 were expressed, but a mutant protein was undetectable by Western blot analysis. L3MBTL1(-/-) mice developed and reproduced normally. The highest expression of L3MBTL1 was detected in the brain, but its disruption did not affect brain development, spontaneous movement, and motor coordination. Despite previous implications of L3mbtl1 in the biology of hematopoietic transcriptional regulators, lack of L3MBTL1 did not result in deficiencies in lymphopoiesis or hematopoiesis. In contrast with its demonstrated biochemical activities, embryonic stem (ES) cells lacking L3MBTL1 displayed no abnormalities in H4 lysine 20 (H4K20) mono-, di-, or trimethylation; had normal global chromatin density as assessed by micrococcal nuclease digests; and expressed normal levels of c-myc. Embryonic fibroblasts lacking L3MBTL1 displayed unaltered cell cycle arrest and down-regulation of cyclin E expression after irradiation. In cohorts of mice followed for more than 2 years, lack of L3MBTL1 did not alter normal lifespan or survival with or without sublethal irradiation. PMID- 20592035 TI - Structural determination of functional domains in early B-cell factor (EBF) family of transcription factors reveals similarities to Rel DNA-binding proteins and a novel dimerization motif. AB - The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID- 20592036 TI - The lipid-binding domain of wild type and mutant alpha-synuclein: compactness and interconversion between the broken and extended helix forms. AB - Alpha-synuclein (alphaS) is linked to Parkinson disease through its deposition in an amyloid fibril form within Lewy Body deposits, and by the existence of three alphaS point mutations that lead to early onset autosomal dominant Parkinsonism. The normal function of alphaS is thought to be linked to the ability of the protein to bind to the surface of synaptic vesicles. Upon binding to vesicles, alphaS undergoes a structural reorganization from a dynamic and disordered ensemble to a conformation consisting of a long extended helix. In the presence of small spheroidal detergent micelles, however, this extended helix conformation can convert into a broken helix state, in which a region near the middle of the helix unwinds to form a linker between the two resulting separated helices. Membrane-bound conformations of alphaS likely mediate the function of the protein, but may also play a role in the aggregation and toxicity of the protein. Here we have undertaken a study of the effects of the three known PD-linked mutations on the detergent- and membrane-bound conformations of alphaS, as well as factors that govern the transition of the protein between the extended helix and broken helix states. Using pulsed dipolar ESR measurements of distances up to 8.7 nm, we show that all three PD-linked alphaS mutants retain the ability to transition from the broken helix to the extended helix conformation. In addition, we find that the ratio of protein to detergent, rather than just the absolute detergent concentration, determines whether the protein adopts the broken or extended helix conformation. PMID- 20592037 TI - para-Aminobenzoic acid is a precursor in coenzyme Q6 biosynthesis in Saccharomyces cerevisiae. AB - Coenzyme Q (ubiquinone or Q) is a crucial mitochondrial lipid required for respiratory electron transport in eukaryotes. 4-Hydroxybenozoate (4HB) is an aromatic ring precursor that forms the benzoquinone ring of Q and is used extensively to examine Q biosynthesis. However, the direct precursor compounds and enzymatic steps for synthesis of 4HB in yeast are unknown. Here we show that para-aminobenzoic acid (pABA), a well known precursor of folate, also functions as a precursor for Q biosynthesis. A hexaprenylated form of pABA (prenyl-pABA) is normally present in wild-type yeast crude lipid extracts but is absent in yeast abz1 mutants starved for pABA. A stable (13)C(6)-isotope of pABA (p- amino[aromatic-(13)C(6)]benzoic acid ([(13)C(6)]pABA)), is prenylated in either wild-type or abz1 mutant yeast to form prenyl-[(13)C(6)]pABA. We demonstrate by HPLC and mass spectrometry that yeast incubated with either [(13)C(6)]pABA or [(13)C(6)]4HB generate both (13)C(6)-demethoxy-Q (DMQ), a late stage Q biosynthetic intermediate, as well as the final product (13)C(6)-coenzyme Q. Pulse-labeling analyses show that formation of prenyl-pABA occurs within minutes and precedes the synthesis of Q. Yeast utilizing pABA as a ring precursor produce another nitrogen containing intermediate, 4-imino-DMQ(6). This intermediate is produced in small quantities in wild-type yeast cultured in standard media and in abz1 mutants supplemented with pABA. We suggest a mechanism where Schiff base mediated deimination forms DMQ(6) quinone, thereby eliminating the nitrogen contributed by pABA. This scheme results in the convergence of the 4HB and pABA pathways in eukaryotic Q biosynthesis and has implications regarding the action of pABA-based antifolates. PMID- 20592038 TI - Surface charges and regulation of FMN to heme electron transfer in nitric-oxide synthase. AB - The nitric-oxide synthases (NOS, EC 1.14.13.39) are modular enzymes containing attached flavoprotein and heme (NOSoxy) domains. To generate nitric oxide (NO), the NOS FMN subdomain must interact with the NOSoxy domain to deliver electrons to the heme for O(2) activation during catalysis. The molecular basis and how the interaction is regulated is unclear. We explored the role of eight positively charged residues that create an electropositive patch on NOSoxy in enabling the electron transfer by incorporating mutations that neutralized or reversed their individual charges. Stopped-flow and steady-state experiments revealed that individual charges at Lys(423), Lys(620), and Lys(660) were the most important in enabling heme reduction in nNOS. Charge reversal was more disruptive than neutralization in all cases, and the effects on heme reduction were not due to a weakening in the thermodynamic driving force for heme reduction. Mutant NO synthesis activities displayed a complex pattern that could be simulated by a global model for NOS catalysis. This analysis revealed that the mutations impact the NO synthesis activity only through their effects on heme reduction rates. We conclude that heme reduction and NO synthesis in nNOS is enabled by electrostatic interactions involving Lys(423), Lys(620), and Lys(660), which form a triad of positive charges on the NOSoxy surface. A simulated docking study reveals how electrostatic interactions of this triad can enable an FMN-NOSoxy interaction that is productive for electron transfer. PMID- 20592039 TI - Imaging cell wall architecture in single Zinnia elegans tracheary elements. AB - The chemical and structural organization of the plant cell wall was examined in Zinnia elegans tracheary elements (TEs), which specialize by developing prominent secondary wall thickenings underlying the primary wall during xylogenesis in vitro. Three imaging platforms were used in conjunction with chemical extraction of wall components to investigate the composition and structure of single Zinnia TEs. Using fluorescence microscopy with a green fluorescent protein-tagged Clostridium thermocellum family 3 carbohydrate-binding module specific for crystalline cellulose, we found that cellulose accessibility and binding in TEs increased significantly following an acidified chlorite treatment. Examination of chemical composition by synchrotron radiation-based Fourier-transform infrared spectromicroscopy indicated a loss of lignin and a modest loss of other polysaccharides in treated TEs. Atomic force microscopy was used to extensively characterize the topography of cell wall surfaces in TEs, revealing an outer granular matrix covering the underlying meshwork of cellulose fibrils. The internal organization of TEs was determined using secondary wall fragments generated by sonication. Atomic force microscopy revealed that the resulting rings, spirals, and reticulate structures were composed of fibrils arranged in parallel. Based on these combined results, we generated an architectural model of Zinnia TEs composed of three layers: an outermost granular layer, a middle primary wall composed of a meshwork of cellulose fibrils, and inner secondary wall thickenings containing parallel cellulose fibrils. In addition to insights in plant biology, studies using Zinnia TEs could prove especially productive in assessing cell wall responses to enzymatic and microbial degradation, thus aiding current efforts in lignocellulosic biofuel production. PMID- 20592041 TI - At the frontier of cultural neuroscience: introduction to the special issue. PMID- 20592040 TI - Ethylene signaling regulates accumulation of the FLS2 receptor and is required for the oxidative burst contributing to plant immunity. AB - Reactive oxygen species (ROS) are potent signal molecules rapidly generated in response to stress. Detection of pathogen-associated molecular patterns induces a transient apoplastic ROS through the function of the NADPH respiratory burst oxidase homologs D (RbohD). However, little is known about the regulation of pathogen-associated molecular pattern-elicited ROS or its role in plant immunity. We investigated ROS production triggered by bacterial flagellin (flg22) in Arabidopsis (Arabidopsis thaliana). The oxidative burst was diminished in ethylene-insensitive mutants. Flagellin Sensitive2 (FLS2) accumulation was reduced in etr1 and ein2, indicating a requirement of ethylene signaling for FLS2 expression. Multiplication of virulent bacteria was enhanced in Arabidopsis lines displaying altered ROS production at early but not late stages of infection, suggesting an impairment of preinvasive immunity. Stomatal closure, a mechanism used to reduce bacterial entry into plant tissues, was abolished in etr1, ein2, and rbohD mutants. These results point to the importance of flg22-triggered ROS at an early stage of the plant immune response. PMID- 20592043 TI - Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity. AB - Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences. PMID- 20592042 TI - Cultural neuroscience of the self: understanding the social grounding of the brain. AB - Cultural neuroscience is an interdisciplinary field of research that investigates interrelations among culture, mind and the brain. Drawing on both the growing body of scientific evidence on cultural variation in psychological processes and the recent development of social and cognitive neuroscience, this emerging field of research aspires to understand how culture as an amalgam of values, meanings, conventions, and artifacts that constitute daily social realities might interact with the mind and its underlying brain pathways of each individual member of the culture. In this article, following a brief review of studies that demonstrate the surprising degree to which brain processes are malleably shaped by cultural tools and practices, the authors discuss cultural variation in brain processes involved in self-representations, cognition, emotion and motivation. They then propose (i) that primary values of culture such as independence and interdependence are reflected in the compositions of cultural tasks (i.e. daily routines designed to accomplish the cultural values) and further (ii) that active and sustained engagement in these tasks yields culturally patterned neural activities of the brain, thereby laying the ground for the embodied construction of the self and identity. Implications for research on culture and the brain are discussed. PMID- 20592044 TI - Theory and methods in cultural neuroscience. AB - Cultural neuroscience is an emerging research discipline that investigates cultural variation in psychological, neural and genomic processes as a means of articulating the bidirectional relationship of these processes and their emergent properties. Research in cultural neuroscience integrates theory and methods from anthropology, cultural psychology, neuroscience and neurogenetics. Here, we review a set of core theoretical and methodological challenges facing researchers when planning and conducting cultural neuroscience studies, and provide suggestions for overcoming these challenges. In particular, we focus on the problems of defining culture and culturally appropriate experimental tasks, comparing neuroimaging data acquired from different populations and scanner sites and identifying functional genetic polymorphisms relevant to culture. Implications of cultural neuroscience research for addressing current issues in population health disparities are discussed. PMID- 20592045 TI - Getting the details right: gene signatures for cancer therapy. PMID- 20592046 TI - Adopting and assimilating new non-pharmaceutical technologies into health care: a systematic review. AB - OBJECTIVE: To explore what is known about organizational processes that determine whether (and the extent and rate at which) new non-pharmaceutical technologies are adopted and assimilated into routine health care. METHODS: Electronic searching of four databases, hand searching of six journals and electronic citation tracking searches of three key research papers. A narrative synthesis was conducted. RESULTS: Ninety-nine empirical studies and seven narrative overviews informed the findings. The majority (62%) of the studies took a deterministic approach (mainly using cross-sectional mailed questionnaires) and typically studied the impact of organizational variables - such as organizational size - on the rate of adoption of technological innovations. The remaining studies were process-based using a single- or multi-case study approach. The organizational processes that determine whether and how technological innovations are adopted and assimilated into routine health care practice are dependent upon the specific innovation concerned, the different actors involved at various points in time, and the particular organizational context in which decisions are made. It is important to see 'adoption' and 'assimilation' as part of an ongoing process rather than discrete events, and as a process that comprises both 'formal' organizational and 'informal' decisions by individual users (the latter often shaped by discussions with their peers and colleagues). CONCLUSIONS: Further process-based studies are needed to provide a clearer evidence base for recommendations on how to facilitate the adoption and assimilation of beneficial new technologies. Three theoretical perspectives could form the basis of such studies and produce practical advice for managers and practitioners. PMID- 20592047 TI - Who's that sleeping in my bed? Potential and actual utilization of public and private in-patient beds in Irish acute public hospitals. AB - OBJECTIVE: To examine the impact of the unusual public/private mix on public and private in-patient bed utilization within Irish acute public hospitals. METHODS: Data from the Department of Health and Children and the Hospital In-Patient Enquiry were used to estimate and compare potential and actual utilization of public and private designated in-patient beds in 54 acute public hospitals from 2000 to 2004. RESULTS: Private in-patients used more bed days than were potentially available to them in 14.1% of hospital-year observations. The equivalent figure for public in-patients was 12.6%. Although the prevalence of excess utilization of private beds was relatively small, it did increase over the study period. Hospitals with excess private utilization were characterized by a relatively low proportion of private- or non-designated beds despite their patient profile being broadly similar to that of hospitals where there was no excess private utilization. CONCLUSIONS: Despite policies designed to limit private practice in Irish acute public hospitals, some hospitals have apparently been able to overcome these restrictions. In a system where financial incentives to treat private patients exist both for consultants and hospitals, it is not clear whether this excess private practice in public hospitals reflects a more efficient utilization of resources (when demand from public patients is low) or the displacement of public patients in favour of private patients. However, that a smaller number on hospital waiting lists possess private health insurance provides some support for the displacement hypothesis. Thus, it appears that policy-makers may need to reconsider attempts to ensure an appropriate division of acute public hospital resources between public and private patients. PMID- 20592048 TI - Relational and management continuity survey in patients with multiple long-term conditions. AB - OBJECTIVE: To quantify problems of relational and management continuity of care in patients with multiple long-term conditions. METHODS: A mailed questionnaire survey was conducted among people aged 60 years and older from 15 general practices. The questionnaire included 16 items concerning relational and management continuity of care. The number of long-term conditions was measured using the Self-Administered Comorbidity Questionnaire. RESULTS: Data were analysed for 1,125 participants, a response rate of 37%. There were 123 (11%) with no long-term conditions, 225 (20%) with one, 284 (25%) with two, 218 (19%) with three and 275 (24%) with four or more. Factor analysis confirmed two factors with seven items for management continuity (alpha 0.88) and nine items for relational continuity (alpha 0.83). Experiences of difficulties with management continuity were higher in participants with three long-term conditions or more (adjusted odds ratio 2.01, 95% confidence interval 1.09 to 3.73), with 'poor' self-rated health (2.21, 1.21 to 4.02), or at least three hospital outpatient attendances each year (2.60, 1.32 to 5.12). The number of long-term conditions was not consistently associated with relational continuity. Difficulties of relational continuity were experienced by participants with 'poor' self-rated health (2.11, 1.16 to 3.85). Patients with more frequent general practice consultations experienced fewer difficulties of relational continuity (0.63, 0.42 to 0.92). CONCLUSION: People with many long-term conditions are at increased risk of inadequate management continuity with potential negative impacts on their care. Experiences of relational continuity, with potential buffering effects, are not associated with the number of long-term conditions. PMID- 20592049 TI - Pharmacological effects of cannabinoids on the Caco-2 cell culture model of intestinal permeability. AB - Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion, and intestinal motility. However, the effects of cannabinoids on intestinal permeability have not yet been established. The aim of the present study is to examine the effects of cannabinoids on intestinal permeability in an in vitro model. Caco-2 cells were grown until fully confluent on inserts in 12 well plates. Transepithelial electrical resistance (TEER) measurements were made as a measure of permeability. EDTA (50 MUM) was applied to reversibly increase permeability (reduce TEER). The effects of cannabinoids on permeability in combination with EDTA, or alone, were assessed. Potential target sites of action were investigated using antagonists of the cannabinoid (CB)(1) receptor, CB(2) receptor, transient receptor potential vanilloid subtype 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)gamma, PPARalpha, and a proposed cannabinoid receptor. When applied to the apical or basolateral membrane of Caco 2 cells, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) enhanced the speed of recovery of EDTA-induced increased permeability. This effect was sensitive to cannabinoid CB(1) receptor antagonism only. Apical application of endocannabinoids caused increased permeability, sensitive to cannabinoid CB(1) receptor antagonism. By contrast, when endocannabinoids were applied basolaterally, they enhanced the recovery of EDTA-induced increased permeability, and this involved additional activation of TRPV1. All cannabinoids tested increased the mRNA of the tight junction protein zona occludens-1, but only endocannabinoids also decreased the mRNA of claudin-1. These findings suggest that endocannabinoids may play a role in modulating intestinal permeability and that plant-derived cannabinoids, such as THC and CBD, may have therapeutic potential in conditions associated with abnormally permeable intestinal epithelium. PMID- 20592050 TI - Initiating insulin as part of the Treating To Target in Type 2 Diabetes (4-T) trial: an interview study of patients' and health professionals' experiences. AB - OBJECTIVE: To explore patients' and health professionals' experiences of initiating insulin as part of the Treating To Target in Type 2 Diabetes (4-T) randomized controlled trial. RESEARCH DESIGN AND METHODS: Interviews were conducted with 45 trial participants and 21 health professionals and thematically analyzed. RESULTS: Patients were generally psychologically insulin receptive when approached to participate in the 4-T trial. Their receptiveness arose largely from their personal experiences observing intensifying prior treatments and deteriorating blood glucose control over time, which led them to engage with and accept the idea that their diabetes was progressive. Health professionals also fostered receptiveness by drawing on their clinical experience to manage patients' anxieties about initiating insulin. CONCLUSIONS: Previous studies may have overemphasized the problem of psychological insulin resistance and overlooked factors and treatment experiences that may promote insulin receptiveness among type 2 patients. PMID- 20592051 TI - Interactions among related genes of renin-angiotensin system associated with type 2 diabetes. AB - OBJECTIVE: To explore the association between epistasis among related genes of the renin-angiotensin system (RAS) and type 2 diabetes. RESEARCH DESIGN AND METHODS: Gene polymorphisms were genotyped in 394 type 2 diabetic patients and 418 healthy control subjects in this case-control study. We used the multifactor dimensionality reduction method to identify gene-gene interactions. RESULTS: No single locus was associated with type 2 diabetes, except for the insert/deletion (I/D) polymorphism of the ACE gene in female subjects. In multi-locus analyses, in male subjects the model of rs2106809 (ACE2), rs220721 (Mas), rs699 (AGT), and I/D (ACE) was significant (P = 0.043). This combination was associated with a 4.00 times (95% CI 2.51-6.38; P < 0.0001) greater prevalence of type 2 diabetes. In female subjects, the model of rs2106809 (ACE2), I/D (ACE), and rs1403543 (AGTR2) was significant (P = 0.012). This three-locus combination was associated with a 2.76 times (1.91-3.97; P < 0.0001) greater prevalence of type 2 diabetes. CONCLUSIONS: Interactions among RAS-related genes were associated with type 2 diabetes in a Chinese population. PMID- 20592053 TI - Effect of juvenile pretraining on adolescent structural hippocampal attributes as a substrate for enhanced spatial performance. AB - Research has demonstrated that Long-Evans rats (LER) display superior mnemonic function over Wistar rats (WR). These differences are correlated with endogenous and input-dependent properties of the hippocampus. The present work sought to determine if juvenile pretraining might enhance hippocampal structural markers and if this would be associated with spatial processing improvements. Male and female WR and LER were either handled or trained on a water maze task from postnatal day 16 (p16) to p26 (pretraining). All animals were then trained on the task from p40 to p44 followed by immunohistochemical assessment of synaptophysin (to mark presynaptic terminals), MAP-2 (to mark dendrites), and the phosphorylated (activated) form of the extracellular signal-regulated kinase-1 (pERK1) in the hippocampus. From p19 to p20, LER (both male and female) showed a dramatic improvement in locating the hidden platform compared to their WR counterparts. On the first day of training at p40, all pretrained groups showed shorter latencies to locate the platform compared to groups without pretraining. Over the next 4 d, only pretrained male LER showed enhanced memory. Immunohistochemical analysis revealed fewer pERK1-labeled neurons in the CA3 hippocampal region in all pretrained groups and fewer pERK1-labeled neurons in the CA1 region of pretrained male LER. Pretrained male LER also showed more MAP-2 staining in CA1 and dentate gyrus regions. Synaptophysin staining revealed a pattern of axonal redistribution in the CA3 region in the pretrained groups. Results suggest a pattern of structural hippocampal alterations that may help to identify network malleability following pretraining protocols. PMID- 20592052 TI - From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation. AB - OBJECTIVE: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered pre-diabetes states. There are limited data in pediatrics in regard to their pathophysiology. We investigated differences in insulin sensitivity and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 24 obese adolescents with NGT, 13 with IFG, 29 with IGT, 11 with combined IFG/IGT, and 30 with type 2 diabetes underwent evaluation of hepatic glucose production ([6,6-(2)H(2)]glucose), insulin stimulated glucose disposal (R(d), euglycemic clamp), first- and second-phase insulin secretion (hyperglycemic clamp), body composition (dual-energy X-ray absorptiometry), abdominal adiposity (computed tomography), and substrate oxidation (indirect calorimetry). RESULTS: Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. R(d) was lower (P = 0.009) in adolescents with type 2 diabetes than in those with NGT. Compared with adolescents with NGT, first-phase insulin was lower in those with IFG, IGT, and IFG/IGT with further deterioration in those with type 2 diabetes (P < 0.001), and beta-cell function relative to insulin sensitivity (glucose disposition index [GDI]) was also lower in those with IFG, IGT, and IFG/IGT (40, 47, and 47%, respectively), with a further decrease (80%) in those with type 2 diabetes (P < 0.001). GDI was the major determinant of fasting and 2 h glucose levels. CONCLUSIONS: Obese adolescents who show signs of glucose dysregulation, including abnormal fasting glucose, glucose intolerance or both, are more likely to have impaired insulin secretion rather than reduced insulin sensitivity. Given the impairment in insulin secretion, they are at high risk for progression to type 2 diabetes. Further deterioration in insulin sensitivity or secretion may enhance the risk for this progression. PMID- 20592055 TI - Are actuarial risk data used to make determinations of sex offender risk classification? An examination of sex offenders selected for enhanced registration and notification. AB - This study examined whether evaluators use actuarial risk scores and risk information to make determinations about sex offender risk status for the purpose of enhanced registration and notification. Although it was expected that sexual offenders selected for enhanced registration and notification would have higher scores on actuarial risk assessment tools than those who were not selected, few differences were found between groups with regard to risk factors associated with sexual offense recidivism. Given that actuarial tools enhance the prediction of sexual recidivism, this study may shed light on problems in the implementation of sex offender policy measures. Results are discussed as they pertain to the assessment and application of registration and community notification statutes for sexual offenders. PMID- 20592054 TI - Protein phosphatase 1-dependent transcriptional programs for long-term memory and plasticity. AB - Gene transcription is essential for the establishment and the maintenance of long term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and phosphatases (PPs) are important players in these mechanisms. Protein serine/threonine phosphatase 1 (PP1), in particular, was recently shown to be important for transcription-dependent memory by regulating chromatin remodeling. However, the impact of PP1 on gene transcription in adult neurons remains not fully delineated. Here, we demonstrate that the nuclear pool of PP1 is associated with transcriptional events involving molecular components of signaling cascades acting as positive and negative regulators of memory and brain plasticity. The data show that inhibiting this pool selectively in forebrain neurons improves memory performance, enhances long-term potentiation (LTP), and modulates gene transcription. These findings highlight an important role for PP1 in the regulation of gene transcription in LTM and synaptic plasticity in the adult brain. PMID- 20592056 TI - Overcoming barriers to conducting an intervention study of depression in an older African American population. AB - The purpose of this article is to describe barriers and strengths of a study testing the effects of reminiscence on depressive symptoms in community-dwelling older African Americans. Primary data sources included debriefing sessions, reflective journals, participant observations, and key informant interviews. Data were analyzed using immersion/crystallization technique. Mistrust between gatekeepers and universities, recruitment and retention of research assistants and participants, culturally insensitive instruments, and stigma associated with depression were barriers. Successful approaches used to overcome the barriers experienced by the research team are described. Implications for transcultural nursing research and practice are discussed. PMID- 20592057 TI - Developing a short form of the simple Rathus assertiveness schedule using a sample of adults with sickle cell disease. AB - PURPOSE: Ethnic and cultural norms influence an individual's assertiveness. In health care, assertiveness may play an important role in health outcomes, especially for predominantly minority populations, such as adults with sickle cell disease. Therefore, it is important to develop measures to accurately assess assertiveness. It is also important to reduce response burden of lengthy instruments while retaining instrument reliability and validity. The purpose of this article is to describe development of a shorter version of the Simple Rathus Assertiveness Schedule (SRAS). DESIGN: Data from a cross-sectional descriptive study of adults with sickle cell disease were used to construct a short form of the SRAS, guided by stepwise regression analysis. RESULTS: The 19-item Simple Rathus Assertiveness Scale-Short Form (SRAS-SF) had acceptable reliability (alpha = .81) and construct validity and was highly correlated with the SRAS (r = .98, p = .01). CONCLUSIONS: The SRAS-SF reduces response burden, while maintaining reliability and validity. PMID- 20592058 TI - An integrative approach to cultural competence education for advanced practice nurses. AB - A project funded by Health Resources and Services Administration (HRSA) provided the impetus for the development of four cultural competence modules taught in a graduate program at a university-based school of nursing. These modules have been consistently taught for 6 years. The authors describe the modules' content, educational strategies, required faculty training, and evaluation and measurement of outcomes. The authors recommend use of the modules and make suggestions for future implementation. Cultural competence is essential for 21st-century practice. The impending national and global health care crises require educational approaches that are cost-effective and tested. These modules are recommended to meet this educational challenge. PMID- 20592059 TI - Partner violence against Korean immigrant women. AB - The purpose of this review article is to explore the phenomenon of partner violence against Korean immigrant women in the United States by using an ecological model. Analysis of the macrosystem (Korean cultural factors), exosystem (immigration stress), and microsystem (marital power dynamic, family role transitions) factors and personal history and characteristics of Korean male batterers (alcohol use and avoidant attachment style) are examined. The health impact of partner violence in family members and recommendations to decrease the violence are discussed. PMID- 20592060 TI - The role of parental history of hypertension in predicting hypertension risk factors in Black Americans. AB - PURPOSE: Black Americans have the highest prevalence of hypertension (HTN) in the United States. HTN has multiple contributors including hereditary, social, psychological, and lifestyle factors. The purpose of this study was to compare HTN risk factors in Black Americans with and without parental history of HTN. DESIGN: Using a descriptive-correlational design, a secondary analysis was conducted with data from 211 participants (64 men and 147 women) between 25 and 79 years of age. FINDINGS: Parental history of HTN, body mass index (BMI), age, gender, and income explained almost 25% (R(2) = .249) of the variance in systolic blood pressure (SBP) and 15% (R(2) = .152) of the variance in diastolic blood pressure (DBP). Neither SBP (t = 1.921, p = .056) nor DBP (t = .993, p = .332) differed significantly based on parental history of HTN, although those with parental history of HTN (n = 102) were significantly younger (t = 3.955, p = .001). BMI was significantly related to blood pressure (BP) (b = 1.323, p <. 001). CONCLUSION: Parental history of HTN was not strongly associated with HTN risk factors or BP in this sample. PRACTICE IMPLICATIONS: Regardless of family history, clinicians should implement strategies that target obesity in Black Americans who are at high risk for developing HTN. PMID- 20592061 TI - Parent perspectives from a neonatal intensive care unit: a missing piece of the culturally congruent care puzzle. AB - The majority of existing theoretical models and tools of culturally competent and congruent care have been developed from the health care provider perspective. Recently, the Culturally Congruent Care Puzzle proposed a model in the form of a three-dimensional puzzle with a provider level and a client level that interact to create the outcome level, which is culturally congruent care. However, the constructs that comprise the client, or patient, level, have not yet been clearly articulated. This study explored parent (client/patient) perceptions of culturally congruent care within a tertiary neonatal intensive care unit based on interviews with culturally diverse families with hospitalized infants (n = 21). The findings identified four primary constructs in the client/patient level: (a) a provider-client relationship of caring and trust, (b) respectful and appropriate communication, (c) culturally responsive and accessible social and spiritual supports, and (d) a welcoming and flexible organizational environment. These four interconnecting pieces are infused with the sociopolitical history and dynamics of culture, ethnicity, immigration, and colonization that clients/patients bring to their experience of health and health care. These elements of the client/patient level also interact with the provider level in various ways. PMID- 20592062 TI - Retention of Native American nurses working in their communities. AB - PURPOSE: The purpose of this study was to describe the experiences of Native American nurses working in their tribal communities to address retention. DESIGN: An interpretive phenomenological study guided by a Native American research agenda and a Native American nursing practice model. METHODS: In-depth interviews with nine Native American nurses were conducted. Data analysis used interpretive phenomenological procedures including an iterative process with Native American consultants and researchers to develop themes. CONCLUSIONS: Native American nurses experienced a great deal of stress and illness as they attempted to fulfill their mission to help their people. The three themes were: (a) paying the price to fulfill my mission, (b) being and connecting holistically, and (c) transcending the system. Recommendations include strategies for nurse educators, tracking the ethnicity of nurses in each Indian Health Service area, documenting their reasons for leaving, and conducting further research to develop community based interventions to improve retention. PMID- 20592063 TI - Stigmatization of persons with HIV/AIDS in Saudi Arabia. AB - Data about the stigmatization of persons living with HIV/AIDS in Saudi Arabia are scarce. Recent statistics from Saudi Ministry of Health showed that 77% of HIV positive Saudis were males. The present study analyzed data from 162 Saudi male college students. The findings suggest that students who knew less about HIV/AIDS were more likely to stigmatize persons living with HIV/AIDS than those who knew more. Neither degree of religiosity nor worry about HIV infection was related to AIDS stigma. However, AIDS-related shame was the best predictor of AIDS stigma. The findings of this study point to important suggestions for AIDS prevention programs in Saudi Arabia. PMID- 20592064 TI - Organizational culture, quality of work life, and organizational effectiveness in Korean university hospitals. AB - PURPOSE: This study investigated correlates and predictors of organizational effectiveness, focusing on organizational culture and quality of work life. DESIGN: Convenience sample of 145 nurses working in Korean university hospitals responded to a self-administered questionnaire. FINDINGS: There were significant correlations between organizational culture, quality of work life, and organizational effectiveness. R2 was 44.7% in the hierarchical multiple regression model, explaining and predicting organizational effectiveness. DISCUSSION: Intact organizational culture and quality of work life for nurses will undoubtedly lead to improved organizational effectiveness. Without efficient and effective nursing care, desired patient outcomes cannot be achieved. PMID- 20592065 TI - The meaning of widowhood and health to older middle-class Hindu widows living in a South Indian community. AB - Indian widowhood has long been associated with victimization and vulnerability, but traditional attitudes toward widowhood are changing and reflect the rapid changes occurring in India. Using Caring Inquiry, a phenomenological-hermeneutic methodology that places caring at its center, this article presents a study that explores the meaning of health and widowhood to 14 older middle-class Hindu widows living in urban South India. From the data emerge six metathemes that are pertinent to nursing praxis and the delivery of health care to widows in South India: (a) Drawing From Within, (b) Seeking Help and Guidance, (c) Accepting the Role, (d) Challenging Tradition, (e) Serving Others, and (f) Finding Companionship. The findings reveal that all the widows share a common desire to move on with life, articulated by one widow as "The Show Must Go On," which serves as a foundation for a theory and model of the meaning of widowhood and health to older middle-class South Indian Hindu widows. This study advances the limited body of knowledge on the lives and health of these widows. PMID- 20592066 TI - Social support, stress, and practice of prenatal care in married immigrant women in Korea. AB - PURPOSE: This study aimed to identify the correlations among social support, stress, and practice of prenatal care and elucidate the predictors affecting the practice of prenatal care in married immigrant women in Korea. METHOD: This study employed a descriptive correlational DESIGN: Social support and prenatal-care practice were positively correlated, and stress was negatively correlated with both prenatal-care practice and social support. The practice of prenatal care in married immigrant women was most influenced by social support. CONCLUSION: As such, there is a need for nursing intervention that fosters social support for pregnant immigrant women. Concerted efforts are also required to reduce their stressors. This study could form the basis for developing childbirth management programs for pregnant women who have immigrated to Korea in order to marry. PMID- 20592067 TI - Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma. AB - To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy. PMID- 20592068 TI - Moderate influence of human APOBEC3F on HIV-1 replication in primary lymphocytes. AB - Multiple APOBEC3 proteins are expressed in HIV-1 target cells, but their individual contributions to viral suppression when expressed at endogenous levels remain largely unknown. We used an HIV NL4-3 mutant that selectively counteracts APOBEC3G (A3G) but not APOBEC3F (A3F) to dissect the relative contribution of A3F to the inhibition of HIV-1 replication in primary human lymphocytes (peripheral blood mononuclear cells [PBMCs]). This HIV Vif mutant replicated similarly to wild-type virus in PBMCs, suggesting that the effect of A3F on HIV restriction in these cells is limited. The different A3F variants found in PMBC donors displayed either comparable activity or less activity than wild-type A3F. Lastly, the endogenous A3F mRNA and protein expression levels in PBMCs were considerably lower than those of A3G. Our results suggest that A3F neutralization is dispensable for HIV-1 replication in primary human T-lymphocytes. PMID- 20592069 TI - Memory CD4 T cells direct protective responses to influenza virus in the lungs through helper-independent mechanisms. AB - Memory CD4 T cells specific for influenza virus are generated from natural infection and vaccination, persist long-term, and recognize determinants in seasonal and pandemic influenza virus strains. However, the protective potential of these long-lived influenza virus-specific memory CD4 T cells is not clear, including whether CD4 T-cell helper or effector functions are important in secondary antiviral responses. Here we demonstrate that memory CD4 T cells specific for H1N1 influenza virus directed protective responses to influenza virus challenge through intrinsic effector mechanisms, resulting in enhanced viral clearance, recovery from sublethal infection, and full protection from lethal challenge. Mice with influenza virus hemagglutinin (HA)-specific memory CD4 T cells or polyclonal influenza virus-specific memory CD4 T cells exhibited protection from influenza virus challenge that occurred in the presence of CD8 depleting antibodies in B-cell-deficient mice and when CD4 T cells were transferred into lymphocyte-deficient RAG2(-/-) mice. Moreover, the presence of memory CD4 T cells mobilized enhanced T-cell recruitment and immune responses in the lung. Neutralization of gamma interferon (IFN-gamma) production in vivo abrogated memory CD4 T-cell-mediated protection from influenza virus challenge by HA-specific memory T cells and heterosubtypic protection by polyclonal memory CD4 T cells. Our results indicate that memory CD4 T cells can direct enhanced protection from influenza virus infection through mobilization of immune effectors in the lung, independent of their helper functions. These findings have important implications for the generation of universal influenza vaccines by promoting long-lived protective CD4 T-cell responses. PMID- 20592070 TI - A disulfide-bonded dimer of the core protein of hepatitis C virus is important for virus-like particle production. AB - Hepatitis C virus (HCV) core protein forms the nucleocapsid of the HCV particle. Although many functions of core protein have been reported, how the HCV particle is assembled is not well understood. Here we show that the nucleocapsid-like particle of HCV is composed of a disulfide-bonded core protein complex (dbc complex). We also found that the disulfide-bonded dimer of the core protein (dbd core) is formed at the endoplasmic reticulum (ER), where the core protein is initially produced and processed. Mutational analysis revealed that the cysteine residue at amino acid position 128 (Cys128) of the core protein, a highly conserved residue among almost all reported isolates, is responsible for dbd-core formation and virus-like particle production but has no effect on the replication of the HCV RNA genome or the several known functions of the core protein, including RNA binding ability and localization to the lipid droplet. The Cys128 mutant core protein showed a dominant negative effect in terms of HCV-like particle production. These results suggest that this disulfide bond is critical for the HCV virion. We also obtained the results that the dbc-complex in the nucleocapsid-like structure was sensitive to proteinase K but not trypsin digestion, suggesting that the capsid is built up of a tightly packed structure of the core protein, with its amino (N)-terminal arginine-rich region being concealed inside. PMID- 20592071 TI - High variability and rapid evolution of a nanovirus. AB - Nanoviruses are multipartite single-stranded DNA (ssDNA) plant viruses that cause important diseases of leguminous crops and banana. Little has been known about the variability and molecular evolution of these viruses. Here we report on the variability of faba bean necrotic stunt virus (FBNSV), a nanovirus from Ethiopia. We found mutation frequencies of 7.52 x 10(-4) substitutions per nucleotide in a field population of the virus and 5.07 x 10(-4) substitutions per nucleotide in a laboratory-maintained population derived thereof. Based on virus propagation for a period of more than 2 years, we determined a nucleotide substitution rate of 1.78 x 10(-3) substitutions per nucleotide per year. This high molecular evolution rate places FBNSV, as a representative of the family Nanoviridae, among the fastest-evolving ssDNA viruses infecting plants or vertebrates. PMID- 20592072 TI - Nonintegrating foamy virus vectors. AB - Foamy viruses (FVs), or spumaviruses, are integrating retroviruses that have been developed as vectors. Here we generated nonintegrating foamy virus (NIFV) vectors by introducing point mutations into the highly conserved DD35E catalytic core motif of the foamy virus integrase sequence. NIFV vectors produced high-titer stocks, transduced dividing cells, and did not integrate. Cells infected with NIFV vectors contained episomal vector genomes that consisted of linear, 1-long terminal-repeat (1-LTR), and 2-LTR circular DNAs. These episomes expressed transgenes, were stable, and became progressively diluted in the dividing cell population. 1-LTR circles but not 2-LTR circles were found in all vector stocks prior to infection. Residual integration of NIFV vectors occurred at a frequency 4 logs lower than that of integrase-proficient FV vectors. Cre recombinase expressed from a NIFV vector mediated excision of both an integrated, floxed FV vector and a gene-targeted neo expression cassette, demonstrating the utility of these episomal vectors. The broad host range and large packaging capacity of NIFV vectors should make them useful for a variety of applications requiring transient gene expression. PMID- 20592073 TI - Stress-inducible alternative translation initiation of human cytomegalovirus latency protein pUL138. AB - We have previously characterized a 21-kDa protein encoded by UL138 (pUL138) as a viral factor inherent to low-passage strains of human cytomegalovirus (HCMV) that is required for latent infection in vitro. pUL138 is encoded on 3.6-, 2.7-, and 1.4-kb 3' coterminal transcripts that are produced during productive and latent infections. pUL138 is encoded at the 3' end of each transcript and is preceded by an extensive 5' sequence (approximately 0.5 to 2.5 kb) containing several putative open reading frames (ORFs). We determined that three putative ORFs upstream of UL138 (UL133, UL135, and UL136) encode proteins. The UL138 transcripts are polycistronic, such that each transcript expresses pUL138 in addition to the most-5' ORF. The upstream coding sequences (CDS) present a significant challenge for the translation of pUL138 in mammalian cells. We hypothesized that sequences 5' of UL138 mediate translation initiation of pUL138 by alternative strategies. Accordingly, a 663-nucloetide (nt) sequence overlapping the UL136 CDS supported expression of a downstream cistron in a bicistronic reporter system. We did not detect cryptic promoter activity or RNA splicing events that could account for downstream cistron expression. These data are consistent with the sequence element functioning as an internal ribosome entry site (IRES). Interestingly, pUL138 expression from the 3.6- and 2.7-kb transcripts was induced by serum stress, which concomitantly inhibited normal cap dependent translation. Our work suggests that an alternative and stress-inducible strategy of translation initiation ensures expression of pUL138 under a variety of cellular contexts. The UL138 polycistronic transcripts serve to coordinate the expression of multiple proteins, including a viral determinant of HCMV latency. PMID- 20592074 TI - RNA 5'-triphosphatase activity of the hepatitis E virus helicase domain. AB - Hepatitis E virus (HEV) has a positive-sense RNA genome with a 5'-m7G cap. HEV open reading frame 1 (ORF1) encodes a polyprotein with multiple enzyme domains required for replication. HEV helicase is a nucleoside triphosphatase (NTPase) with the ability to unwind RNA duplexes in the 5'-to-3' direction. When incubated with 5'-[gamma-(32)P]RNA and 5'-[alpha-(32)P]RNA, HEV helicase released (32)P only from 5'-[gamma-(32)P]RNA, showing specificity for the gamma-beta triphosphate bond. Removal of gamma-phosphate from the 5' end of the primary transcripts (pppRNA to ppRNA) by RNA triphosphatase is an essential step during cap formation. It is suggested that HEV employs the helicase to mediate the first step of 5' cap synthesis. PMID- 20592075 TI - Reduced fitness in cell culture of HIV-1 with nonnucleoside reverse transcriptase inhibitor-resistant mutations correlates with relative levels of reverse transcriptase content and RNase H activity in virions. AB - Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of multidrug therapy for HIV-1. Understanding the effect of NNRTI resistant mutants on virus replication and reverse transcriptase (RT) function is valuable for the development of extended-spectrum NNRTIs. We measured the fitness of six NNRTI-resistant mutants, the K103N, V106A, Y181C, G190A, G190S, and P236L viruses, using a flow cytometry-based cell culture assay. K103N and Y181C viruses had fitness similar to that of the wild type while V106A, G190A, G190S, and P236L viruses had reduced fitness. We also determined the biochemical correlates of fitness by measuring the RNase H and polymerization activities of recombinant mutant RTs and virion-associated RTs. The RNase H activities of recombinant and virion-associated RTs correlated with the relative fitness for each mutant. K103N and Y181C mutants had normal RNase H activity; V106A, G190A, and G190S mutants had moderate reductions in activity; and the P236L mutant had substantially reduced activity. With the exception of the P236L mutant, reduced fitness correlates with low virion-associated polymerization efficiency and reduced RT content. Reduced polymerase function in virions derived from low RT content rather than an intrinsic polymerization defect in each RT protein. In conclusion, severe defects in RNase H activity alone, exemplified by the P236L mutant, appear sufficient to cause a substantial reduction in fitness. For the other NNRTI mutants, reductions in RT content decreased both polymerization and RNase H activity in virions. RNase H reduction was compounded by intrinsic RNase H defects in the mutant RTs. PMID- 20592076 TI - All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. AB - The hepatitis C virus (HCV) nonstructural protein NS5A is critical for viral genome replication and is thought to interact directly with both the RNA dependent RNA polymerase, NS5B, and viral RNA. NS5A consists of three domains which have, as yet, undefined roles in viral replication and assembly. In order to define the regions that mediate the interaction with RNA, specifically the HCV 3' untranslated region (UTR) positive-strand RNA, constructs of different domain combinations were cloned, bacterially expressed, and purified to homogeneity. Each of these purified proteins was probed for its ability to interact with the 3' UTR RNA using filter binding and gel electrophoretic mobility shift assays, revealing differences in their RNA binding efficiencies and affinities. A specific interaction between domains I and II of NS5A and the 3' UTR RNA was identified, suggesting that these are the RNA binding domains of NS5A. Domain III showed low in vitro RNA binding capacity. Filter binding and competition analyses identified differences between NS5A and NS5B in their specificities for defined regions of the 3' UTR. The preference of NS5A, in contrast to NS5B, for the polypyrimidine tract highlights an aspect of 3' UTR RNA recognition by NS5A which may play a role in the control or enhancement of HCV genome replication. PMID- 20592077 TI - Dendritic cells loaded with tumor B cells elicit broad immunity against murine gammaherpesvirus 68 but fail to prevent long-term latency. AB - It is still unknown whether a noninfectious gammaherpesvirus vaccine is able to prevent or reduce virus persistence. This led us to use dendritic cells loaded with tumor B cells as a vaccine approach for the murine gammaherpesvirus 68 (gammaHV68) model of infection. Dendritic cells loaded with UV-irradiated latently infected tumor B cells induce broad, strong, and long-lasting immunity against gammaHV68. Dendritic cell vaccination prevents the enlargement of lymph nodes and severely limits acute infection and early latency but does not prevent gammaHV68 from establishing long-term latency. Our findings support the concept that attenuated viruses may be the best vaccine option for preventing gammaherpesvirus persistence. PMID- 20592078 TI - Mycobacterium tuberculosis promotes HIV trans-infection and suppresses major histocompatibility complex class II antigen processing by dendritic cells. AB - Mycobacterium tuberculosis is a leading killer of HIV-infected individuals worldwide, particularly in sub-Saharan Africa, where it is responsible for up to 50% of HIV-related deaths. Infection by HIV predisposes individuals to M. tuberculosis infection, and coinfection accelerates the progression of both diseases. In contrast to most other opportunistic infections associated with HIV, an increased risk of M. tuberculosis infection occurs during early-stage HIV disease, long before CD4 T cell counts fall below critical levels. We hypothesized that M. tuberculosis infection contributes to HIV pathogenesis by interfering with dendritic cell (DC)-mediated immune control. DCs carry pathogens like M. tuberculosis and HIV from sites of infection into lymphoid tissues, where they process and present antigenic peptides to CD4 T cells. Paradoxically, DCs can also deliver infectious HIV to T cells without first becoming infected, a process known as trans-infection. Lipopolysaccharide (LPS)-activated DCs sequester HIV in pocketlike membrane invaginations that remain open to the cell surface, and individual virions are delivered from the pocket into T cells at the site of contact during trans-infection. Here we report that M. tuberculosis exposure increases HIV trans-infection and induces viral sequestration within surface-accessible compartments identical to those seen in LPS-stimulated DCs. At the same time, M. tuberculosis dramatically decreases the degradative processing and major histocompatibility complex class II (MHC-II) presentation of HIV antigens to CD4 T cells. Our data suggest that M. tuberculosis infection promotes a shift in the dynamic balance between antigen processing and intact virion presentation, favoring DC-mediated amplification of HIV infections. PMID- 20592079 TI - Human enterovirus 109: a novel interspecies recombinant enterovirus isolated from a case of acute pediatric respiratory illness in Nicaragua. AB - Enteroviruses (Picornaviridae family) are a common cause of human illness worldwide and are associated with diverse clinical syndromes, including asymptomatic infection, respiratory illness, gastroenteritis, and meningitis. In this study, we report the identification and complete genome sequence of a novel enterovirus isolated from a case of acute respiratory illness in a Nicaraguan child. Unbiased deep sequencing of nucleic acids from a nose and throat swab sample enabled rapid recovery of the full-genome sequence. Phylogenetic analysis revealed that human enterovirus 109 (EV109) is most closely related to serotypes of human enterovirus species C (HEV-C) in all genomic regions except the 5' untranslated region (5' UTR). Bootstrap analysis indicates that the 5' UTR of EV109 is likely the product of an interspecies recombination event between ancestral members of the HEV-A and HEV-C groups. Overall, the EV109 coding region shares 67 to 72% nucleotide sequence identity with its nearest relatives. EV109 isolates were detected in 5/310 (1.6%) of nose and throat swab samples collected from children in a pediatric cohort study of influenza-like illness in Managua, Nicaragua, between June 2007 and June 2008. Further experimentation is required to more fully characterize the pathogenic role, disease associations, and global distribution of EV109. PMID- 20592080 TI - Identification of a gp41 core-binding molecule with homologous sequence of human TNNI3K-like protein as a novel human immunodeficiency virus type 1 entry inhibitor. AB - Human immunodeficiency virus type 1 (HIV-1) gp41 plays a critical role in the viral fusion process, and its N- and C-terminal heptad repeat domains serve as important targets for developing anti-HIV-1 drugs, like T-20 (generic name, enfuvirtide; brand name, Fuzeon). Here, we conducted a yeast two-hybrid screening on a human bone marrow cDNA library using the recombinant soluble gp41 ectodomain as the bait and identified a novel gp41 core-binding molecule, designated P20. P20 showed no homology with a current HIV fusion inhibitor, T-20, but had sequence homology to a human protein, troponin I type 3 interacting kinase (TNNI3K)-like protein. While it could bind to the six-helix bundle core structure formed by the N- and C-terminal heptad repeats, P20 did not interrupt the formation of the six-helix bundle. P20 was effective in blocking HIV-1 Env mediated syncytium formation and inhibiting infection by a broad spectrum of HIV 1 strains with distinct subtypes and coreceptor tropism, while it was ineffective against other enveloped viruses, such as vesicular stomatitis virus and influenza A virus. P20 exhibited no significant cytotoxicity to the CD4(+) cells that were used for testing antiviral activity. Among the 11 P20 mutants, four analogous peptides with a common motif (WGRLEGRRT) exhibited significantly reduced anti-HIV 1 activity, suggesting that this region is the critical active site of P20. Therefore, this peptide can be used as a lead for developing novel HIV fusion inhibitors and as a probe for studying the membrane-fusogenic mechanism of HIV. PMID- 20592081 TI - The architecture and chemical stability of the archaeal Sulfolobus turreted icosahedral virus. AB - Viruses utilize a diverse array of mechanisms to deliver their genomes into hosts. While great strides have been made in understanding the genome delivery of eukaryotic and prokaryotic viruses, little is known about archaeal virus genome delivery and the associated particle changes. The Sulfolobus turreted icosahedral virus (STIV) is a double-stranded DNA (dsDNA) archaeal virus that contains a host derived membrane sandwiched between the genome and the proteinaceous capsid shell. Using cryo-electron microscopy (cryo-EM) and different biochemical treatments, we identified three viral morphologies that may correspond to biochemical disassembly states of STIV. One of these morphologies was subtly different from the previously published 27-A-resolution electron density that was interpreted with the crystal structure of the major capsid protein (MCP). However, these particles could be analyzed at 12.5-A resolution by cryo-EM. Comparing these two structures, we identified the location of multiple proteins forming the large turret-like appendages at the icosahedral vertices, observed heterogeneous glycosylation of the capsid shell, and identified mobile MCP C terminal arms responsible for tethering and releasing the underlying viral membrane to and from the capsid shell. Collectively, our studies allow us to propose a fusogenic mechanism of genome delivery by STIV, in which the dismantled capsid shell allows for the fusion of the viral and host membranes and the internalization of the viral genome. PMID- 20592082 TI - Replication of subgenomic hepatitis C virus replicons in mouse fibroblasts is facilitated by deletion of interferon regulatory factor 3 and expression of liver specific microRNA 122. AB - Hepatitis C virus (HCV) infection causes significant morbidity, and efficient mouse models would greatly facilitate virus studies and the development of effective vaccines and new therapeutic agents. Entry factors, innate immunity, and host factors needed for viral replication represent the initial barriers that restrict HCV infection of mouse cells. Experiments in this paper consider early postentry steps of viral infection and investigate the roles of interferon regulatory factors (IRF-3 and IRF-9) and microRNA (miR-122) in promoting HCV replication in mouse embryo fibroblasts (MEFs) that contain viral subgenomic replicons. While wild-type murine fibroblasts are restricted for HCV RNA replication, deletion of IRF-3 alone can facilitate replicon activity in these cells. This effect is thought to be related to the inactivation of the type I interferon synthesis mediated by IRF-3. Additional deletion of IRF-9 to yield IRF 3(-/-) IRF-9(-/-) MEFs, which have blocked type I interferon signaling, did not increase HCV replication. Expression of liver-specific miR-122 in MEFs further stimulated the synthesis of HCV replicons in the rodent fibroblasts. The combined effects of miR-122 expression and deletion of IRF-3 produced a cooperative stimulation of HCV subgenome replication. miR-122 and IRF-3 are independent host factors that are capable of influencing HCV replication, and our findings could help to establish mouse models and other cell systems that support HCV growth and particle formation. PMID- 20592083 TI - Identification of a critical T(Q/D/E)x5ADx2(I/L) motif from primate lentivirus Vif proteins that regulate APOBEC3G and APOBEC3F neutralizing activity. AB - Primate lentiviruses are unique in that they produce several accessory proteins to help in the establishment of productive viral infection. The major function of these proteins is to clear host resistance factors that inhibit viral replication. Vif is one of these proteins. It functions as an adaptor that binds to the cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) and bridges them to a cullin 5 (Cul5) and elongin (Elo) B/C E3 ubiquitin ligase complex for proteasomal degradation. So far, 11 discontinuous domains in Vif have been identified that regulate this degradation process. Here we report another domain, T(Q/D/E)x(5)ADx(2)(I/L), which is located at residues 96 to 107 in the human immunodeficiency virus type 1 (HIV-1) Vif protein. This domain is conserved not only in all HIV-1 subtypes but also in other primate lentiviruses, including HIV 2 and simian immunodeficiency virus (SIV), which infects rhesus macaques (SIVmac) and African green monkeys (SIVagm). Mutations of the critical residues in this motif seriously disrupted Vif's neutralizing activity toward both A3G and A3F. This motif regulates Vif interaction not only with A3G and A3F but also with Cul5. When this motif was inactivated in the HIV-1 genome, Vif failed to exclude A3G and A3F from virions, resulting in abortive HIV replication in nonpermissive human T cells. Thus, T(Q/D/E)x(5)ADx(2)(I/L) is a critical functional motif that directly supports the adaptor function of Vif and is an attractive target for inhibition of Vif function. PMID- 20592084 TI - Adaptation of pandemic H1N1 influenza viruses in mice. AB - The molecular mechanism by which pandemic 2009 influenza A viruses were able to sufficiently adapt to humans is largely unknown. Subsequent human infections with novel H1N1 influenza viruses prompted an investigation of the molecular determinants of the host range and pathogenicity of pandemic influenza viruses in mammals. To address this problem, we assessed the genetic basis for increased virulence of A/CA/04/09 (H1N1) and A/TN/1-560/09 (H1N1) isolates, which are not lethal for mice, in a new mammalian host by promoting their mouse adaptation. The resulting mouse lung-adapted variants showed significantly enhanced growth characteristics in eggs, extended extrapulmonary tissue tropism, and pathogenicity in mice. All mouse-adapted viruses except A/TN/1-560/09-MA2 grew faster and to higher titers in cells than the original strains. We found that 10 amino acid changes in the ribonucleoprotein (RNP) complex (PB2 E158G/A, PA L295P, NP D101G, and NP H289Y) and hemagglutinin (HA) glycoprotein (K119N, G155E, S183P, R221K, and D222G) controlled enhanced mouse virulence of pandemic isolates. HA mutations acquired during adaptation affected viral receptor specificity by enhancing binding to alpha2,3 together with decreasing binding to alpha2,6 sialyl receptors. PB2 E158G/A and PA L295P amino acid substitutions were responsible for the significant enhancement of transcription and replication activity of the mouse-adapted H1N1 variants. Taken together, our findings suggest that changes optimizing receptor specificity and interaction of viral polymerase components with host cellular factors are the major mechanisms that contribute to the optimal competitive advantage of pandemic influenza viruses in mice. These modulators of virulence, therefore, may have been the driving components of early evolution, which paved the way for novel 2009 viruses in mammals. PMID- 20592085 TI - Gene expression differences in lungs of mice during secondary immune responses to respiratory syncytial virus infection. AB - Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (DeltaG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following DeltaG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication. PMID- 20592086 TI - Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus. AB - Type I interferons (IFNs) play a critical role in the host defense against viruses. Lymphocytic choriomeningitis virus (LCMV) infection induces robust type I IFN production in its natural host, the mouse. However, the mechanisms underlying the induction of type I IFNs in response to LCMV infection have not yet been clearly defined. In the present study, we demonstrate that IRF7 is required for both the early phase (day 1 postinfection) and the late phase (day 2 postinfection) of the type I IFN response to LCMV, and melanoma differentiation associated gene 5 (MDA5)/mitochondrial antiviral signaling protein (MAVS) signaling is crucial for the late phase of the type I IFN response to LCMV. We further demonstrate that LCMV genomic RNA itself (without other LCMV components) is able to induce type I IFN responses in various cell types by activation of the RNA helicases retinoic acid-inducible gene I (RIG-I) and MDA5. We also show that expression of the LCMV nucleoprotein (NP) inhibits the type I IFN response induced by LCMV RNA and other RIG-I/MDA5 ligands. These virus-host interactions may play important roles in the pathogeneses of LCMV and other human arenavirus diseases. PMID- 20592087 TI - Inhibition of cellular proteasome activities mediates HBX-independent hepatitis B virus replication in vivo. AB - The X protein (HBX) of the hepatitis B virus (HBV) is essential for HBV productive infection in vivo. Our previous study (Z. Hu, Z. Zhang, E. Doo, O. Coux, A. L. Goldberg, and T. J. Liang, J. Virol. 73:7231-7240, 1999) shows that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. Previously, we demonstrated that HBX affects hepadnaviral replication through a proteasome-dependent pathway in cell culture models. In the present study, we studied the effect of the proteasome inhibitor MLN-273 in two HBV mouse models. We demonstrated that administration of MLN-273 to transgenic mice containing the replication-competent HBV genome with the defective HBX gene substantially enhanced HBV replication, while the compound had a minor effect on wild-type HBV transgenic mice. Similar results were obtained by using C57BL/6 mice infected with recombinant adenoviruses expressing the replicating HBV genome. Our data suggest that HBV replication is subjected to regulation by cellular proteasome and HBX functions through the inhibition of proteasome activities to enhance HBV replication in vivo. PMID- 20592088 TI - Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2. AB - Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine is available. Protection against DENV and other related flaviviruses is associated with the development of antibodies against the viral envelope (E) protein. Although prior studies have characterized the neutralizing activity of monoclonal antibodies (MAbs) against DENV type 2 (DENV-2), none have compared simultaneously the inhibitory activity against a genetically diverse range of strains in vitro, the protective capacity in animals, and the localization of epitopes. Here, with the goal of identifying MAbs that can serve as postexposure therapy, we investigated in detail the functional activity of a large panel of new anti-DENV-2 mouse MAbs. Binding sites were mapped by yeast surface display and neutralization escape, cell culture inhibition assays were performed with homologous and heterologous strains, and prophylactic and therapeutic activity was evaluated with two mouse models. Protective MAbs localized to epitopes on the lateral ridge of domain I (DI), the dimer interface, lateral ridge, and fusion loop of DII, and the lateral ridge, C-C' loop, and A strand of DIII. Several MAbs inefficiently inhibited at least one DENV-2 strain of a distinct genotype, suggesting that recognition of neutralizing epitopes varies with strain diversity. Moreover, antibody potency generally correlated with a narrowed genotype and serotype specificity. Five MAbs functioned efficiently as postexposure therapy when administered as a single dose, even 3 days after intracranial infection of BALB/c mice. Overall, these studies define the structural and functional complexity of antibodies against DENV-2 with protective potential. PMID- 20592089 TI - Foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells. AB - Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin alphav beta6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-beta) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-beta mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-alpha mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response. PMID- 20592090 TI - Alpha/beta interferon (IFN-alpha/beta)-independent induction of IFN-lambda1 (interleukin-29) in response to Hantaan virus infection. AB - Type III interferons ([IFNs] IFN-lambda and interleukin-28 and -29 [IL-28/29]) are recently recognized cytokines with innate antiviral effects similar to those of type I IFNs (IFN-alpha/beta). Like IFN-alpha/beta, IFN-lambda-expression can be induced by viruses, and it is believed that type I and III IFNs are regulated in the same manner. Hantaviruses are weak IFN-alpha/beta inducers and have surprisingly been shown to activate IFN-alpha/beta-independent IFN-stimulated gene (ISG) expression. Here, we show that in Hantaan virus (HTNV)-infected human epithelial A549 cells, induction of IFN-lambda1 preceded induction of MxA and IFN beta by 12 and 24 h, respectively, and IFN-alpha was not induced at all. Furthermore, induction of IFN-lambda1 and MxA was observed in HTNV-infected African green monkey epithelial Vero E6 cells, a cell line that cannot produce type I IFNs, clearly showing that HTNV can induce IFN-lambda1 and ISGs in the complete absence of IFN-alpha/beta. In HTNV-infected human fibroblast MRC-5 cells, which lack the IFN-lambda receptor, induction of MxA coincided in time with IFN-beta-induction. UV-inactivated HTNV did not induce any IFNs or MxA in any cell line, showing that activation of IFN-lambda1 is dependent on replicating virus. Induction of both IFN-beta and IFN-lambda1 in A549 cells after poly(I:C) stimulation was strongly inhibited in HTNV-infected cells, suggesting that HTNV can inhibit signaling pathways used to simultaneously activate types I and III IFNs. In conclusion, we show that HTNV can cause type I IFN-independent IFN lambda1 induction and IFN-lambda1-specific ISG induction. Importantly, the results suggest the existence of specific signaling pathways that induce IFN lambda1 without simultaneous type I IFN induction during virus infection. PMID- 20592091 TI - Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge. AB - An effective human immunodeficiency virus (HIV) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. To determine whether our best simian immunodeficiency virus (SIV) vaccine can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac239Delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition of SIVsmE660 in comparison to that for naive controls (log rank test; P = 0.023). After 10 mucosal challenges, we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these 10 challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than did the naive controls (Mann-Whitney U test; P = 0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 postinfection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequence analysis of the circulating viruses in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication. PMID- 20592092 TI - Expression of MIP-1alpha (CCL3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and B cells. AB - Previously, we showed that overexpression of MIP-1alpha in mouse brain further decreased rabies virus (RABV) pathogenicity (L. Zhao, H. Toriumi, Y. Kuang, H. Chen, and Z. F. Fu, J. Virol., 83:11808-11818, 2009). In the present study, the immunogenicity of recombinant RABV expressing MIP-1alpha (rHEP-MIP1alpha) was determined. It was found that intramuscular immunization of BALB/c mice with rHEP MIP1alpha resulted in a higher level of expression of MIP-1alpha at the site of inoculation, increased recruitment of dendritic cells (DCs) and mature B cells into the draining lymph nodes and the peripheral blood, and higher virus neutralizing antibody titers than immunization with the parent rHEP and recombinant RABVs expressing RANTES (CCL5) or IP-10 (CXCL10). Our data thus demonstrate that expression of MIP-1alpha not only reduces viral pathogenicity but also enhances immunogenicity by recruiting DCs and B cells to the site of immunization, the lymph nodes, and the blood. PMID- 20592093 TI - Mutational mapping of UL130 of human cytomegalovirus defines peptide motifs within the C-terminal third as essential for endothelial cell infection. AB - The UL130 gene is one of the major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV). In order to define functionally important peptides within this protein, we have performed a charge-cluster-to-alanine (CCTA) mutational scanning of UL130 in the genetic background of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain. A total of 10 charge clusters were defined, and in each of them two or three charged amino acids were replaced with alanines. While the six N-terminal clusters were phenotypically irrelevant, mutation of the four C-terminal clusters each caused a reduction of EC tropism. The importance of this protein domain was further emphasized by the fact that the C-terminal pentapeptide PNLIV was essential for infection of ECs, and the cell tropism could not be rescued by a scrambled version of this sequence. We conclude that the C terminus of the UL130 protein serves an important function for infection of ECs by HCMV. This makes UL130 a promising molecular target for antiviral strategies, e.g., the development of antiviral peptides. PMID- 20592094 TI - Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in respiratory syncytial virus (RSV)-challenged naive and formalin-inactivated RSV-immunized BALB/c mice. AB - We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')(2) forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines. PMID- 20592095 TI - A short N-terminal peptide motif on flavivirus nonstructural protein NS1 modulates cellular targeting and immune recognition. AB - Flavivirus NS1 is a versatile nonstructural glycoprotein, with intracellular NS1 functioning as an essential cofactor for viral replication and cell surface and secreted NS1 antagonizing complement activation. Even though NS1 has multiple functions that contribute to virulence, the genetic determinants that regulate the spatial distribution of NS1 in cells among different flaviviruses remain uncharacterized. Here, by creating a panel of West Nile virus-dengue virus (WNV DENV) NS1 chimeras and site-specific mutants, we identified a novel, short peptide motif immediately C-terminal to the signal sequence cleavage position that regulates its transit time through the endoplasmic reticulum and differentially directs NS1 for secretion or plasma membrane expression. Exchange of two amino acids within this motif reciprocally changed the cellular targeting pattern of DENV or WNV NS1. For WNV, this substitution also modulated infectivity and antibody-induced phagocytosis of infected cells. Analysis of a mutant lacking all three conserved N-linked glycosylation sites revealed an independent requirement of N-linked glycans for secretion but not for plasma membrane expression of WNV NS1. Collectively, our experiments define the requirements for cellular targeting of NS1, with implications for the protective host responses, immune antagonism, and association with the host cell sorting machinery. These studies also suggest a link between the effects of NS1 on viral replication and the levels of secreted or cell surface NS1. PMID- 20592096 TI - Genetic and phenotypic characterization of GII-4 noroviruses that circulated during 1987 to 2008. AB - The predominance and continual emergence of new variants in GII-4 noroviruses (NVs) in recent years have raised questions about the role of host immunity and histo-blood group antigens (HBGAs) in NV evolution. To address these questions, we performed a genetic and phenotypic characterization of GII-4 variants circulating in the past decade (1998 to 2008). Ninety-three GII-4 sequences were analyzed, and of them, 16 strains representing 6 genetic clusters were selected for further characterization. The HBGA binding properties were determined by both saliva- and oligosaccharide-binding assays using P particles as a model of NV capsid. The antigenic properties were also examined by enzyme immunoassay (EIA), Western blot analysis, and receptor blocking assay, using P-particle-specific antibodies from immunized mice and GII-4 virus-infected patients. Our results showed that 15 of the 16 GII-4 viruses bound to saliva of all A, B, and O secretors. Oligosaccharide binding assays yielded largely consistent results, although the binding affinities to some oligosaccharides varied among some strains. The only nonbinder had a mutation in the binding site. While antigenic variations were detected among the 16 strains, significant cross-blocking on the HBGA binding was also noted. Sequence alignment revealed high conservation of HBGA binding interfaces with some variations in adjacent regions. Taken together, our data suggested that the ability of GII-4 to recognize different secretor HBGAs persisted over the past decade, which may explain the predominance of GII-4 over other genotypes. Our data also indicated that both the host immunity and HBGAs play a role in NV evolution. While host immunity may continue driving NV for antigenic change, the functional selection by the HBGAs tends to lock the architecture of the capsid/HBGA interfaces and allows only limited variations outside the HBGA binding sites. A potential outcome of such counterselection between theses two factors in NV evolution is discussed. PMID- 20592097 TI - Mutational and metal binding analysis of the endonuclease domain of the influenza virus polymerase PA subunit. AB - Influenza virus polymerase initiates the biosynthesis of its own mRNAs with capped 10- to 13-nucleotide fragments cleaved from cellular (pre-)mRNAs. Two activities are required for this cap-snatching activity: specific binding of the cap structure and an endonuclease activity. Recent work has shown that the cap binding site is situated in the central part of the PB2 subunit and that the endonuclease activity is situated in the N-terminal domain of the PA subunit (PA Nter). The influenza endonuclease is a member of the PD-(D/E)XK family of nucleases that use divalent metal ions for nucleic acid cleavage. Here we analyze the metal binding and endonuclease activities of eight PA-Nter single-point mutants. We show by calorimetry that the wild-type active site binds two Mn(2+) ions and has a 500-fold higher affinity for manganese than for magnesium ions. The endonuclease activity of the isolated mutant domains are compared with the cap-dependent transcription activities of identical mutations in trimeric recombinant polymerases previously described by other groups. Mutations that inactivate the endonuclease activity in the isolated PA-Nter knock out the transcription but not replication activity in the recombinant polymerase. We confirm the importance of a number of active-site residues and identify some residues that may be involved in the positioning of the RNA substrate in the active site. Our results validate the use of the isolated endonuclease domain in a drug-design process for new anti-influenza virus compounds. PMID- 20592099 TI - Early initiation of continuous ambulatory peritoneal dialysis in patients undergoing surgical implantation of Tenckhoff catheters. AB - BACKGROUND: Nephrologists commonly recommend continuous ambulatory peritoneal dialysis (CAPD) with break-in periods of at least 2 weeks. We investigated the safety and feasibility of shorter break-in periods following surgical implantation of Tenckhoff catheters. METHODS: We retrospectively examined 310 patients that underwent Tenckhoff catheter implantation for the first time. The early group comprised 226 patients that started CAPD <= 14 days after implantation; the late group comprised 84 patients that started CAPD > 14 days after implantation. Catheter-related complications within 6 months were analyzed. RESULTS: A total of 310 patients were enrolled. Time to CAPD initiation was shorter in the early group (2.0 +/- 2.7 days) than in the late group (40.6 +/- 42.8 days) (p < 0.001). The bridge hemodialysis rate was higher in the late group (57.1%) than in the early group (31.4%) (p < 0.001). Overall, 33 early-group (14.6%) and 11 late-group patients (13.1%) developed catheter-related complications within 6 months. The early-group complications were leakage (n = 5), diminished outflow volume (n = 7), migration (n = 7), pericatheter hernia (n = 1), hemoperitoneum (n = 1), pericatheter infection (n = 3), and peritonitis (n = 9). The late-group complications were leakage (n = 2), diminished outflow volume (n = 5), migration (n = 2), and peritonitis (n = 2). Actuarial freedom from catheter-related complications was similar in both groups (log rank, p = 0.76). CONCLUSION: Early initiation of CAPD with surgically implanted Tenckhoff catheters is feasible and safe. Shorter break-in periods are not associated with more catheter-related complications. The data from our peritoneal dialysis population suggest that early initiation is not associated with an increased number of complications. This needs to be confirmed in a randomized trial. PMID- 20592098 TI - The clinically approved proteasome inhibitor PS-341 efficiently blocks influenza A virus and vesicular stomatitis virus propagation by establishing an antiviral state. AB - Recently it has been shown that the proinflammatory NF-kappaB pathway promotes efficient influenza virus propagation. Based on these findings, it was suggested that NF-kappaB blockade may be a promising approach for antiviral intervention. The classical virus-induced activation of the NF-kappaB pathway requires proteasomal degradation of the inhibitor of NF-kappaB, IkappaB. Therefore, we hypothesized that inhibition of proteasomal IkappaB degradation should impair influenza A virus (IAV) replication. We chose the specific proteasome inhibitor PS-341, which is a clinically approved anticancer drug also known as Bortezomib or Velcade. As expected, PS-341 treatment of infected A549 cells in a concentration range that was not toxic resulted in a significant reduction of progeny virus titers. However, we could not observe the proposed suppression of NF-kappaB-signaling in vitro. Rather, PS-341 treatment resulted in an induction of IkappaB degradation and activation of NF-kappaB as well as the JNK/AP-1 pathway. This coincides with enhanced expression of antiviral genes, such as interleukin-6 and, most importantly, MxA, which is a strong interferon (IFN) induced suppressor of influenza virus replication. This suggests that PS-341 may act as an antiviral agent via induction of the type I IFN response. Accordingly, PS-341 did not affect virus titers in Vero cells, which lack type I IFN genes, but strongly inhibited replication of vesicular stomatitis virus (VSV), a highly IFN-sensitive pathogen. Thus, we conclude that PS-341 blocks IAV and VSV replication by inducing an antiviral state mediated by the NF-kappaB-dependent expression of antivirus-acting gene products. PMID- 20592100 TI - Normalized bioimpedance indices are better predictors of outcome in peritoneal dialysis patients. AB - BACKGROUND: While phase angle of bioimpedance analysis (BIA) has great survival predicting value in dialysis populations, it is known to be higher in male than in female subjects. In this study, we aimed to explore the factors influencing the predictive value of phase angle and to identify the appropriate physics terms for normalizing capacitance (C) and resistance (R). METHODS: We formulated body capacitive index (BCI), C(BMI) (capacitance * height(2)/weight), body resistive index (BRI), R(BMI) (resistance * weight/height(2)), and CH(2) (capacitance * height(2)). We also studied H(2)/R, R/H, and reactance of a capacitor/height (X(C) /H). There are 3 components in this study design: (1) establishment of normal values in a control Malaysian population, (2) comparison of these with a CAPD population, and (3) prediction of survival within a CAPD population. We initially performed a BIA study in 206 female and 116 male healthy volunteers, followed by a prospective study in a cohort of 128 CAPD patients [47 with diabetes mellitus (DM), 81 non-DM; 59 males, 69 females] for at least 2 years. All the parameters during enrolment, including BIA, serum albumin, peritoneal equilibrium test, age, and DM status, were analyzed. Outcome measurement was survival. RESULTS: In healthy volunteers, both genders had the same BCI (2.0 nF kg/m(2)). On the contrary, female normal subjects had higher BRI than male normal subjects (median 15 642 vs 13242 Omega kg/m(2), p < 0.001) due to higher fat percentage (35.4% +/- 0.4% vs 28.0% +/- 0.6%, p < 0.001), resulting in a lower phase angle (mean 5.82 +/- 0.04 vs 6.86 +/- 0.07 degrees, p < 0.001). Logistic regression showed that BCI was the best risk indicator in 128 CAPD patients versus 322 normal subjects. In age- and body mass index (BMI)-matched head-to head comparison, BCI had the highest chi(2) value (chi(2) = 102.63), followed by CH(2) (or H(2)/X(C); chi(2) = 81.00), BRI (chi(2) = 20.54), and X(C)/H (chi(2) = 20.48), with p value < 0.001 for these parameters. In comparison, phase angle (chi(2) = 11.42), R/H (chi(2) = 7.19), and H(2)/R (chi(2) = 5.69) had lower chi(2) values. 35 (27.3%) patients died during the study period. Univariate analysis adjusted for DM status and serum albumin level demonstrated that non surviving patients had significantly higher CH(2) (245 vs 169 nF m(2), p < 0.001) and BCI (4.0 vs 2.9 nF m(2)/kg, p = 0.005) than patients that survived. CH(2) was the best predictor for all-cause mortality in Cox regression analysis, followed by BCI, phase angle, and X(C)/H. CONCLUSION: Measures that normalize, such as BCI and CH(2), have higher risk discrimination and survival prediction ability than measures that do not normalize, such as phase angle. Unlike phase angle, measurement of BCI overcomes the gender effect. In this study, the best risk indicator for CAPD patients versus the general population is BCI, reflecting deficit in nutritional concentration, while CH(2) reflects total nutritional deficit and thus is the major risk indicator for survival of CAPD patients. PMID- 20592101 TI - Linkage of some trace elements, peripheral blood lymphocytes, inflammation, and oxidative stress in patients undergoing either hemodialysis or peritoneal dialysis. AB - BACKGROUND: Changes in essential trace elements may affect the inflammatory and immunological state of patients on hemodialysis (HD) or peritoneal dialysis (PD). Therefore, we aimed to determine trace element content and markers of oxidative stress, inflammation, and immune status in HD and PD patients and to assess the relationships among these parameters. METHODS: Patients on either HD (n = 20) or PD (n = 20) and age-, sex-, body mass index-matched healthy individuals (n = 20) were enrolled in the study. The trace elements zinc, copper, selenium, and iron; markers of oxidative stress thiobarbituric acid reactive substances (TBARS) and protein carbonyl levels; activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase; percentages of CD3 T lymphocytes and the subsets CD4 and CD8; the CD4/CD8 ratio; and C-reactive protein (CRP) were measured. RESULTS: All dialysis patients had low levels of albumin and hemoglobin. Significantly decreased percentages of CD3 and CD4 T lymphocytes and increased levels of CRP, TBARS, and carbonyl compounds were observed in HD patients. HD patients also had elevated erythrocyte SOD, lower GPx and catalase activities, and decreased levels of Se, Zn, and Fe in comparison to PD patients and healthy subjects. In addition, CRP was positively associated with TBARS and carbonyl levels, but was significantly inversely associated with Zn and Se levels. Positive correlations were found between T lymphocyte CD3 and CD4 percentages and Zn, Se, and Fe levels. CONCLUSIONS: There were significant decreases in T lymphocyte-related immunological regulation and increased inflammation and oxidative stress in dialysis patients. Essential trace element status was independently related to immune status, inflammation, and oxidative damage. PMID- 20592102 TI - Executive function and attention regulation as predictors of coping success in youth with functional abdominal pain. AB - OBJECTIVE: To examine the role of executive function and attention regulation in coping and their indirect effects on anxiety and depression through coping in youth with functional abdominal pain. METHODS: Participants (n = 44, mean age = 11.77, SD = 7.16, 68.2% female) and their accompanying caregivers completed measures of executive function, attention regulation, coping, anxiety, and depression during scheduled clinic appointments at a tertiary pediatric medical center. RESULTS: Regression analyses revealed significant relations between selective attention abilities and two different approaches to coping with the stressor of abdominal pain episodes. Bootstrapping procedures for mediation provided evidence for the indirect effects of selective attention and attentional control on anxiety through cognitive coping strategies. CONCLUSIONS: Attention regulation may be an important factor that contributes to the variability in outcomes in youth with functional abdominal pain and should be considered when assessing the coping and psychological adjustment of this population. PMID- 20592103 TI - Plasma folate concentrations are positively associated with risk of estrogen receptor beta negative breast cancer in a Swedish nested case control study. AB - Folate's role in breast cancer development is controversial. Not only estrogen receptor (ER) alpha status, but also ERbeta status of tumors may have confounded results from previous epidemiological studies. We aimed to examine associations between plasma folate concentration and postmenopausal breast cancer defined by ER status. This nested case-control study, within the Malmo diet and cancer cohort, included 204 incident breast cancer cases with information on ERalpha and ERbeta status determined by immunochemistry on tissue micro-array sections. Plasma folate concentration was analyzed for the cases and 408 controls (matched on age and blood sample date). Odds ratios (OR) for ER-defined breast cancers in tertiles of plasma folate concentration were calculated with unconditional logistic regression. All tests were 2-sided. Women in the third tertile of plasma folate concentration (> 12 nmol/L) had higher incidence of ERbeta- breast cancer than women in the first tertile (OR: 2.67; 95% CI: 1.44-4.92; P-trend = 0.001). We did not observe significant associations between plasma folate concentration and other breast cancer subgroups defined by ER status. We observed a difference between risks for ERbeta + and ERbeta- cancer (P-heterogeneity = 0.003). Our findings, which indicate a positive association between plasma folate and ERbeta- breast cancer, highlight the importance of taking ERbeta status into consideration in studies of folate and breast cancer. The study contributes knowledge concerning folate's multifaceted role in cancer development. If replicated in other populations, the observations may have implications for public health, particularly regarding folic acid fortification. PMID- 20592104 TI - Biotin regulates the expression of holocarboxylase synthetase in the miR-539 pathway in HEK-293 cells. AB - Holocarboxylase synthetase (HCS) catalyzes the covalent binding of biotin to carboxylases and histones. In mammals, the expression of HCS depends on biotin, but the mechanism of regulation is unknown. Here we tested the hypothesis that microRNA (miR) plays a role in the regulation of the HCS gene. Human embryonic kidney cells were used as the primary model, but cell lines from other tissues and primary human cells were also tested. In silico searches revealed an evolutionary conserved binding site for miR-539 in the 3 prime -untranslated region (3 prime -UTR) of HCS mRNA. Transgenic cells and reporter gene constructs were used to demonstrate that miR-539 decreases the expression of HCS at the level of transcription rather than translation; these findings were corroborated in nontransgenic cells. When miR-539 was overexpressed in transgenic cells, the abundance of both HCS and biotinylated histones decreased. The abundance of miR 539 was tissue dependent: fibroblasts gt kidney cells gt intestinal cells gt lymphoid cells. Dose-response studies revealed that the abundance of miR-539 was significantly higher at physiological concentrations of biotin than both biotin deficient and biotin-supplemented media in all cell lines tested. In kidney cells, the expression of HCS was lower in cells in physiological medium than in deficient and supplemented medium. In contrast, in fibroblasts, lymphoid cells, and intestinal cells, there was no apparent link between miR-539 abundance and HCS expression, suggesting that factors other than miR-539 also contribute to the regulation of HCS expression in some tissues. Collectively, the results of this study suggest that miR-539 is among the factors sensing biotin and regulating HCS. PMID- 20592106 TI - Reduced sensitivity to cholecystokinin in male rats fed a high-fat diet is reversible. AB - Adult rats chronically fed a high-fat (HF) diet maintain reduced sensitivity to cholecystokinin (CCK). We hypothesized that, similar to adult rats, pups fed a HF diet would also exhibit reduced sensitivity to CCK. To test this, male pups fed low-fat (LF) and HF isoenergetic (16.2 kJ/g) diets were administered CCK intraperitoneally (0.125-1 microg/kg) 1 wk following dietary adaptation. After receiving 0.5 microg/kg CCK, pups fed the HF diet suppressed food intake less (8.9 +/- 5.0%) than pups fed the LF diet (28.9 +/- 4.7%; P < 0.05) relative to intakes after saline administration. We then assessed the development and extinction of changes in CCK sensitivity by switching the diets between the groups. The HF-fed group, when switched to the LF diet, regained sensitivity by wk 4 and suppressed food intake following administration of 0.25 microg/kg CCK (33.1 +/- 5.7%; P < 0.05). The LF-fed group, when switched to the HF diet, lost sensitivity by wk 2 and did not suppress food intake after administrations of CCK compared with saline. Finally, we examined if HF-fed rats have an increased sensitivity to corn oil during brief access tests using a multibottle gustometer. At oil concentrations of 25, 75, and 100%, rats fed the HF diet sampled more oil than LF-fed rats (P < 0.05). These findings demonstrate that male rat pups fed a HF diet exhibit reduced sensitivity to CCK, the development of this reduced sensitivity is quicker than its extinction, and rats consuming a HF diet have increased oral sensitivity to oils. PMID- 20592105 TI - Diet-induced obesity in mice reduces the maintenance of influenza-specific CD8+ memory T cells. AB - Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8(+) memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor beta (IL-2R beta, CD122), but not IL-7 receptor alpha (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population. PMID- 20592107 TI - Size and mechanical stability of norovirus capsids depend on pH: a nanoindentation study. AB - Norovirus-like particles were imaged using atomic force microscopy. The mechanical stability of the virus-like particles (VLPs) was probed by nanoindentation at pH values ranging from 2 to 10. This range includes pH values of the natural environment during the life cycle of noroviruses. The resistance of VLPs to indentation was constant at acidic and neutral pH. The Young's modulus was of the order of 30 MPa. At basic pH the compliance of the capsid increased along with an increase in diameter. This specific pH-dependent mechanical response of the capsid may be related to mechanisms controlling uptake and release of the RNA during infection. Consecutive indentations with pressures <= 300 bar demonstrated the ability of the capsids to fully recover from deformations comparable with the size of the capsid. The capsids can be viewed as nanocontainers with an inbuilt self-repair mechanism. At pH 10 the capsids lost their stability and were irreversibly destroyed after one single indentation. PMID- 20592109 TI - Identification of a novel phosphorylation site in hepatitis C virus NS5A. AB - Hepatitis C virus (HCV) NS5A protein is phosphorylated on multiple residues; however, despite extensive study, the precise identity of these sites has not been determined unambiguously. In this study, we have used a combination of immunoprecipitation and mass spectrometry to identify these phosphorylation sites. This analysis revealed the presence of a major phosphorylated residue within NS5A from the genotype 1b Con1 isolate - serine 249 (serine 2221 in polyprotein numbering). However, mutation of this residue (or the corresponding threonine in the JFH-1 isolate) to either a phosphomimetic (aspartate) or a phosphoablative (alanine) residue resulted in no phenotype. We conclude that phosphorylation of this residue, in the context of a highly culture-adapted HCV genome, does not play a role in either viral RNA replication or virus assembly. It is possible that it might be important in an aspect of virus biology that is not recapitulated faithfully in the Huh-7 cell-culture system. PMID- 20592108 TI - Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam. AB - Vietnam is one of the countries most affected by highly pathogenic H5N1 influenza A viruses. To evaluate the potential pathogenicity in mammals of H5N1 viruses isolated from humans in Vietnam, we determined the sequences of all eight genes of 22 human isolates collected between 2003 and 2008 and compared their virulence in mice. The isolates were classified into clade 1 and clade 2.3.4 and differed in pathogenicity for mice. Whilst lysine at position 627 of PB2 (PB2-627K) is a critical virulence determinant for clade 2.3.4 viruses, asparagine at position 701 of PB2 and other unknown virulence determinants appear to be involved in the high pathogenicity of clade 1 viruses, warranting further studies to determine the factors responsible for the high virulence of H5N1 viruses in mammals. PMID- 20592110 TI - Modification of the major tegument protein pp65 of human cytomegalovirus inhibits virus growth and leads to the enhancement of a protein complex with pUL69 and pUL97 in infected cells. AB - The tegument protein pp65 of human cytomegalovirus (HCMV) is abundant in lytically infected human foreskin fibroblasts (HFF), as well as in virions and subviral dense bodies (DB). Despite this, we showed previously that pp65 is dispensable for growth in HFF. In the process of refining a DB-based vaccine candidate, different HCMV mutants were generated, expressing a dominant HLA-A2 presented peptide of the IE1 protein fused to pp65. One of the mutant viruses (RV VM1) surprisingly showed marked impairment in virus release from HFF. We hypothesized that analysis of the phenotypic alterations of RV-VM1 would provide insight into the functions of pp65, poorly defined thus far. RV-VM1 infection resulted in nuclear retention of the fusion protein and reorganization of nuclear inclusion bodies. Coimmunoprecipitation experiments suggested that wild-type (wt) pp65 and pp65-VM1 were substrates of the viral pUL97 kinase in vitro and formed a complex with the viral RNA-export protein pUL69 and with pUL97 in lysates of infected cells. No evidence for an impairment of pUL97 within this complex was found. However, RV-VM1 replication in infected cells was resistant to a pUL97 inhibitor, and pUL97 inhibitors mimicked the mutant in terms of pp65 being retained in the nucleus. The results suggest that the life cycle of RV-VM1 was impeded at the stages of early-late transcription, RNA export or capsid maturation. wt-pp65 may play a role at these stages of infection, and complex formation with pUL69 and pUL97 may be important for that function. PMID- 20592111 TI - Bovine herpesvirus 4 ORF73 is dispensable for virus growth in vitro, but is essential for virus persistence in vivo. AB - ORF73 orthologues encoded by different rhadinoviruses have been studied extensively. These studies revealed that the ORF73 expression product (pORF73) is a multifunctional protein essential for latency that enables episome tethering to mitotic chromosomes and modulates cellular pathways implicated in growth and survival of latently infected cells. Comparison of pORF73 orthologues encoded by rhadinoviruses reveals important variations in amino acid sequence length and composition. Bovine herpesvirus 4 (BoHV-4) encodes by far the shortest ORF73 orthologue, with a size equivalent to only 22 % of that of the largest orthologues. The present study focused on determining whether BoHV-4 ORF73 is a bona fide gene and investigating whether it is essential for latency, as established for larger ORF73 orthologues. Our results demonstrate that BoHV-4 ORF73 is transcribed as immediate-early polycistronic mRNA together with ORF71. Using a BoHV-4 bacterial artificial chromosome clone, we produced a strain deleted for ORF73 and a revertant strain. Deletion of BoHV-4 ORF73 did not affect the capacity of the virus to replicate in vitro, but it prevented latent infection in vivo using a rabbit model. Interestingly, the strain deleted for ORF73 induced an anti-BoHV-4 humoral immune response comparable to that elicited by the wild type and revertant recombinants. Together, these results demonstrate that, despite its relatively small size, BoHV-4 ORF73 is a functional homologue of larger rhadinovirus ORF73 orthologues, and highlight the potential of ORF73 deletion for the development of BoHV-4 as a vector in vaccinology. PMID- 20592112 TI - Molecular epidemiology of Saint Louis encephalitis virus in the Brazilian Amazon: genetic divergence and dispersal. AB - Saint Louis encephalitis virus (SLEV), a member of the genus Flavivirus (family Flaviviridae), is an encephalitogenic arbovirus broadly distributed in the Americas. Phylogenetic analysis based on the full-length E gene sequences obtained for 30 Brazilian SLEV strains was performed using different methods including Bayesian and relaxed molecular clock approaches. A new genetic lineage was suggested, hereafter named genotype VIII, which co-circulates with the previously described genotype V in the Brazilian Amazon region. Genotypes II and III were restricted to Sao Paulo state (South-east Atlantic rainforest ecosystem). The analysis also suggested the emergence of an SLEV common ancestor between 1875 and 1973 (mean of 107 years ago), giving rise to two major genetic groups: genotype II, more prevalent in the North America, and a second group comprising the other genotypes (I and III-VIII), broadly dispersed throughout the Americas, suggesting that SLEV initially emerged in South America and spread to North America. In conclusion, the current study demonstrates the high genetic variability of SLEV and its geographical dispersion in Brazil and other New World countries. PMID- 20592113 TI - Interleukin-8 production by human airway epithelial cells in response to Pseudomonas aeruginosa clinical isolates expressing type a or type b flagellins. AB - Pseudomonas aeruginosa lung infection is a major cause of morbidity and mortality worldwide. P. aeruginosa flagellin, the main structural protein of the flagellar filament, is a virulence factor with proinflammatory activity on respiratory epithelial cells. P. aeruginosa bacteria express one of two isoforms of flagellin (type a or b) that differ in their primary amino acid sequences as well as in posttranslational glycosylation. In this study, the distribution of type a and b flagellins among 3 P. aeruginosa laboratory strains and 14 clinical isolates (1 ulcerative keratitis, 3 cystic fibrosis, and 10 acute pneumonia isolates) was determined, and their abilities to stimulate interleukin-8 (IL-8) production by human airway epithelial cells was compared. By comparison with the PAK (type a) and PAO1 (type b) prototype laboratory strains, 10/14 (71.4%) of clinical isolates expressed type a and 4/14 (28.6%) expressed type b flagellins. Among four cell lines surveyed, BEAS-2B cells were found to give the greatest difference between constitutive and flagellin-stimulated IL-8 production. All 17 flagellins stimulated IL-8 production by BEAS-2B cells (range, 700 to 4,000 pg/ml). However, no discernible differences in IL-8 production were evident when comparing type a versus type b flagellins or flagellins from laboratory versus clinical strains or among the clinical strains. PMID- 20592114 TI - Immunocapture enzyme-linked immunosorbent assay for assessment of in vitro potency of recombinant hepatitis B vaccines. AB - Quantification of hepatitis B surface antigen (HBsAg) or relative in vitro potency in the final vaccines is a prerequisite for hepatitis B vaccine batch release. The commercial kit for automated analysis (AxSYM) is expensive, and an alternative is required for the estimation of HBsAg in hepatitis B vaccines. Mouse monoclonal antibodies (MAbs) specific for HBsAg were developed and characterized. One of the monoclonal antibodies (HBs06) was used in development of an immunocapture ELISA (IC-ELISA) as an unlabeled capture antibody and biotin labeled detection antibody. The IC-ELISA was standardized and validated using experimental hepatitis B vaccine batches with various HBsAg concentrations per dose and commercial vaccines. The vaccine was treated with an alkaline solubilizer to desorb the HBsAg from Algel-adjuvanted vaccines before testing, and the sensitivity of the test was 5 ng/ml. A good correlation could be observed between the HBsAg estimates derived by both formats, except for the higher HBsAg concentration range, where the IC-ELISA format could estimate closer to the actual values than AxSYM. There was a significant correlation between the estimated relative potencies of the two methods. There was lack of correlation between the in vivo potency and the relative in vitro potency. However, the estimates of IC-ELISA were comparable to the in vivo values when compared with the estimates of AxSYM. The IC-ELISA can therefore be considered to be a reliable test for deriving in vitro relative potency and antigen concentration in vaccine batches for batch control and release. PMID- 20592116 TI - Generation and preservation of the slow underlying membrane potential oscillation in model bursting neurons. AB - The underlying membrane potential oscillation of both forced and endogenous slow wave bursting cells affects the number of spikes per burst, which in turn affects outputs downstream. We use a biophysical model of a class of slow-wave bursting cells with six active currents to investigate and generalize correlations among maximal current conductances that might generate and preserve its underlying oscillation. We propose three phases for the underlying oscillation for this class of cells: generation, maintenance, and termination and suggest that different current modules coregulate to preserve the characteristics of each phase. Coregulation of I(Burst) and I(A) currents within distinct boundaries maintains the dynamics during the generation phase. Similarly, coregulation of I(CaT) and I(Kd) maintains the peak and duration of the underlying oscillation, whereas the calcium-activated I(KCa) ensures appropriate termination of the oscillation and adjusts the duration independent of peak. PMID- 20592115 TI - Major impairments of glutamatergic transmission and long-term synaptic plasticity in the hippocampus of mice lacking the melanin-concentrating hormone receptor-1. AB - The hypothalamic neuropeptide melanin-concentrating hormone (MCH) plays important roles in energy homeostasis, anxiety, and sleep regulation. Since the MCH receptor-1 (MCH-R1), the only functional receptor that mediates MCH functions in rodents, facilitates behavioral performance in hippocampus-dependent learning tasks, we investigated whether glutamatergic transmission in CA1 pyramidal cells could be modulated in mice lacking the MCH-R1 gene (MCH-R1(-/-)). We found that both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl d-aspartate (NMDA) receptor-mediated transmissions were diminished in the mutant mice compared with their controls. This deficit was explained, at least in part, by a postsynaptic down-regulation of these receptors since the amplitude of miniature excitatory postsynaptic currents and the NMDA/AMPA ratio were decreased. Long-term synaptic potentiation (LTP) was also impaired in MCH-R1(-/-) mice. This was due to an altered induction, rather than an impaired, expression because repeating the induction stimulus restored LTP to a normal magnitude. In addition, long-term synaptic depression was strongly diminished in MCH-R1(-/-) mice. These results suggest that MCH exerts a facilitatory effect on CA1 glutamatergic synaptic transmission and long-term synaptic plasticity. Recently, it has been shown that MCH neurons fire exclusively during sleep and mainly during rapid eye movement sleep. Thus these findings provide a mechanism by which sleep might facilitate memory consolidation. PMID- 20592117 TI - Persistent currents and discharge patterns in rat hindlimb motoneurons. AB - We report here the first direct measurements of persistent inward currents (PICs) in rat hindlimb motoneurons, obtained from ketamine-xylazine anesthetized rats during slow voltage ramps performed by single-electrode somatic voltage clamp. Most motoneurons expressed PICs and current-voltage (I-V) relations often contained a negative-slope region (NSR; 13/19 cells). PICs activated at -52.7 +/- 3.89 mV, 9 mV negative to spike threshold. NSR onset was -44.2 +/- 4.1 mV. PIC amplitudes were assessed by maximum inward currents measured relative to extrapolated leak current and to NSR-onset current. PIC conductance at potentials just positive to activation was assessed by the relative change in slope conductance (g(in)/g(leak)). PIC amplitudes varied widely; some exceeded 5 and 10 nA relative to current at NSR onset or leak current, respectively. PIC amplitudes did not vary significantly with input conductance, but PIC amplitudes normalized by recruitment current decreased with increasing input conductance. Similarly, g(in)/g(leak) decreased with increasing input conductance. Currents near resting potential on descending limbs of I-V relations were often outward, relative to ascending-limb currents. This residual outward current was correlated with increases in leak conductance on the descending limb and with input conductance. Excluding responses with accommodation, residual outward currents matched differences between recruitment and derecruitment currents, suggesting a role for residual outward current in frequency adaptation. Comparison of potentials for PIC activation and NSR onset with interspike trajectories during discharge demonstrated correspondence between PIC activation and frequency-current (f-I) range boundaries. Contributions of persistent inward and outward currents to motoneuron discharge characteristics are discussed. PMID- 20592118 TI - Bicuculline-induced chorea manifests in focal rather than globalized abnormalities in the activation of the external and internal globus pallidus. AB - Chorea is a basal-ganglia (BG) related hyperkinetic movement disorder characterized by irregular continuous involuntary movements. Chorea and related hyperbehavioral disorders may be induced in behaving primates by local microinjections of the GABA(A) antagonist bicuculline to the globus pallidus externus (GPe). We performed multielectrode extracellular recordings in the GPe and in the globus pallidus internus (GPi) before, during, and after bicuculline microinjections. Bicuculline led to an increase in the firing rate and a change in the firing pattern of GPe neurons. Two types of abnormal neuronal firing patterns were detected in GPe neurons close to the bicuculline microinjection site: continuous high-frequency activity and bistable activity, in which neurons transitioned between high-frequency and complete cessation of firing. Neuronal activity remained uncorrelated within and between the GPe and the GPi, with no evidence for propagation of the focal GPe abnormal activity downstream to the GPi. Despite reduction in the information capacity of bicuculline-affected GPe neurons, the ability to encode behavioral events was maintained. We found similar responses of GPe neurons to bicuculline in vitro in the rat, suggesting a basic cellular mechanism underlying these abnormal firing patterns. These results demonstrate that chorea is associated with focal neuronal changes that are not complemented by global changes in the BG nuclei. This suggests a mechanism of stochastic phasic alteration of BG control leading to the chaotic nature of chorea. Thus rather than imposing a globalized state of cortical excitability, chorea might be associated with changes in internal information processing within the BG. PMID- 20592119 TI - Characteristics and organization of discharge properties in rat hindlimb motoneurons. AB - The discharge properties of hindlimb motoneurons in ketamine-xylazine anesthetized rats were measured to assess contributions of persistent intrinsic currents to these characteristics and to determine their distribution in motoneuron pools. Most motoneurons (30/37) responded to ramp current injections with adapting patterns of discharge and the frequency-current (f-I) relations of nearly all motoneurons included a steep subprimary range of discharge. Despite the prevalence of adapting f-I relations, responses included indications that persistent inward currents (PICs) were activated, including increased membrane noise and prepotentials before discharge, as well as counterclockwise hysteresis and secondary ranges in f-I relations. Examination of spike thresholds and afterhyperpolarization (AHP) trajectories during repetitive discharge revealed systematic changes in threshold and trajectory within the subprimary, primary, and secondary f-I ranges. These changes in the primary and secondary ranges were qualitatively similar to those described previously for cat motoneurons. Within the subprimary range, AHP trajectories often included shallow approaches to threshold following recruitment and slope of the AHP ramp consistently increased until the subprimary range was reached. We suggest that PICs activated near recruitment contributed to these slope changes and formation of the subprimary range. Discharge characteristics were strongly correlated with motoneuron size, using input conductance as an indicator of size. Discharge adaptation, recruitment current, and frequency increased with input conductance, whereas both subprimary and primary f-I gains decreased. These results are discussed with respect to potential mechanisms and their functional implications. PMID- 20592120 TI - Interspike interval analyses reveal irregular firing patterns at short, but not long, intervals in rat head direction cells. AB - Previous studies have shown that a subset of neurons in the rat anterodorsal thalamus discharge as a function of the animal's head direction (HD) in the horizontal plane, independent of the animal's location and behavior. These cells have consistent firing properties across a wide range of conditions and cell discharge appears highly regular when listened to through a loudspeaker. In contrast, interspike interval (ISI) analyses on cortical cells have found that cell firing is irregular, even under constant stimulus conditions. Here, we analyzed HD cells from the anterodorsal thalamus, while rats foraged for food pellets, to determine whether their firing was regular or irregular. ISIs were measured when the animal's HD was maintained within +/- 6 degrees of the cell's preferred firing direction. ISIs were highly variable with a mean coefficient of variation (CV) of 0.681. For each cell, the CV values at HDs +/- 24 degrees away from the cell's preferred direction were similar to the coefficient measured at the cell's preferred direction. A second recording session showed that cells had similar coefficients of variation as the first session, suggesting that the degree of variability in cell spiking was a characteristic property for each cell. There was little correlation between ISIs and angular head velocity or translational speed. ISIs measured in HD cells from the postsubiculum and lateral mammillary nuclei showed higher CV values. These results indicate that despite the appearance of regularity in their firing, HD cells, like cortical cells, have irregular ISIs. In contrast to the irregular firing observed for ISIs, analyses over longer time intervals indicated that HD cell firing was much more regular, more nearly resembling a rate code. These findings have implications for attractor networks that model the HD signal and for models proposed to explain the generation of grid cell signals in entorhinal cortex. PMID- 20592121 TI - Somatosensory contribution to motor learning due to facial skin deformation. AB - Motor learning is dependent on kinesthetic information that is obtained both from cutaneous afferents and from muscle receptors. In human arm movement, information from these two kinds of afferents is largely correlated. The facial skin offers a unique situation in which there are plentiful cutaneous afferents and essentially no muscle receptors and, accordingly, experimental manipulations involving the facial skin may be used to assess the possible role of cutaneous afferents in motor learning. We focus here on the information for motor learning provided by the deformation of the facial skin and the motion of the lips in the context of speech. We used a robotic device to slightly stretch the facial skin lateral to the side of the mouth in the period immediately preceding movement. We found that facial skin stretch increased lip protrusion in a progressive manner over the course of a series of training trials. The learning was manifest in a changed pattern of lip movement, when measured after learning in the absence of load. The newly acquired motor plan generalized partially to another speech task that involved a lip movement of different amplitude. Control tests indicated that the primary source of the observed adaptation was sensory input from cutaneous afferents. The progressive increase in lip protrusion over the course of training fits with the basic idea that change in sensory input is attributed to motor performance error. Sensory input, which in the present study precedes the target movement, is credited to the target-related motion, even though the skin stretch is released prior to movement initiation. This supports the idea that the nervous system generates motor commands on the assumption that sensory input and kinematic error are in register. PMID- 20592122 TI - Paired-pulse transcranial magnetic stimulation during preparation for simple and choice reaction time tasks. AB - Motor preparation for execution of both simple and choice reaction time tasks (SRT and CRT) involves enhancement of corticospinal excitability (CE). However, motor preparation also implies changes in inhibitory control that have thus far been much less studied. Short-interval intracortical inhibition (SICI) has been shown to decrease before CE increases. Therefore we reasoned that, if SICI contributes to inhibitory control of voluntary movement during the preparatory phase, it would be larger in CRT than in SRT because of the need to keep the movement unreleased until the uncertainty resolves on which task is required. We measured changes in SICI and in CE at different time points preceding motor reaction in normal subjects. Single-pulse transcranial magnetic stimulation (spTMS) and paired-pulse transcranial magnetic stimulation (ppTMS) produced time dependent changes in both SRT and CRT, with shortening when applied close to the presentation of the imperative signal ("early") and lengthening when applied near the expected reaction ("late"). In addition, at all stimulation time points, reaction time was shorter with ppTMS than that with spTMS, but there was no consistent association between the amount of SICI and reaction time changes. At early stimulation time points, CE was reduced in CRT but not in SRT. However, SICI in CRT was not different from SICI in SRT. At late stimulation time points, SICI decreased just before enhancement of CE. Our findings indicate that inhibitory circuits other than SICI are responsible for setting the level of CE at earlier parts of the reaction time period. Although the decrease in SICI may contribute to the increase in CE at the last part of the premotor period, the two phenomena are not dependent on each other. PMID- 20592123 TI - Stimulus novelty, and not neural refractoriness, explains the repetition suppression of laser-evoked potentials. AB - Brief radiant laser pulses selectively activate skin nociceptors and elicit transient brain responses (laser-evoked potentials [LEPs]). When LEPs are elicited by pairs of stimuli (S1-S2) delivered at different interstimulus intervals (ISIs), the S2-LEP is strongly reduced at short ISIs (250 ms) and progressively recovers at longer ISIs (2,000 ms). This finding has been interpreted in terms of order of arrival of nociceptive volleys and refractoriness of neural generators of LEPs. However, an alternative explanation is the modulation of another experimental factor: the novelty of the eliciting stimulus. To test this alternative hypothesis, we recorded LEPs elicited by pairs of nociceptive stimuli delivered at four ISIs (250, 500, 1,000, 2,000 ms), using two different conditions. In the constant condition, the ISI was identical across the trials of each block, whereas in the variable condition, the ISI was varied randomly across trials and single-stimulus trials were intermixed with paired trials. Therefore the time of occurrence of S2 was both less novel and more predictable in the constant than in the variable condition. In the constant condition, we observed a significant ISI-dependent suppression of the biphasic negative-positive wave (N2-P2) complex of the S2-LEP. In contrast, in the variable condition, the S2-LEP was completely unaffected by stimulus repetition. The pain ratings elicited by S2 were not different in the two conditions. These results indicate that the repetition-suppression of the S2-LEP is not due to refractoriness in nociceptive afferent pathways, but to a modulation of novelty and/or temporal predictability of the eliciting stimulus. This provides further support to the notion that stimulus saliency constitutes a crucial determinant of LEP magnitude and that a significant fraction of the brain activity time-locked to a brief and transient sensory stimulus is not directly related to the quality and the intensity of the corresponding sensation, but to bottom-up attentional processes. PMID- 20592124 TI - Repetition suppression dissociates spatial frames of reference in human saccade generation. AB - The path from perception to action involves the transfer of information across various reference frames. Here we applied a functional magnetic resonance imaging (fMRI) repetition suppression paradigm to determine the reference frame(s) in which the cortical activity is coded at several phases of the sensorimotor transformation for a saccade, including sensory processing, saccade planning, and saccade execution. We distinguished between retinal (eye-centered) and nonretinal (e.g., head-centered) coding frames in three key regions: the intraparietal sulcus (IPS), frontal eye field (FEF), and supplementary eye field (SEF). Subjects (n = 18) made delayed saccades to one of five possible peripheral targets, separated at intervals of 9 degrees visual angle. Target locations were chosen pseudorandomly, based on a 2 * 2 factorial design, with factors retinal and nonretinal coordinates and levels novel and repeated. In all three regions, analysis of the blood oxygenation level dependent dynamics revealed an attenuation of the fMRI signal in trials repeating the location of the target in retinal coordinates. The amount of retinal suppression varied across the three phases of the trial, with the strongest suppression during saccade planning. The paradigm revealed only weak traces of nonretinal coding in these regions. Further analyses showed an orderly representation of the retinal target location, as expressed by a contralateral bias of activation, in the IPS and FEF, but not in the SEF. These results provide evidence that the sensorimotor processing in these centers reflects saccade generation in eye-centered coordinates, irrespective of their topographic organization. PMID- 20592125 TI - Short-term effects of single repetitive TMS sessions on auditory evoked activity in patients with chronic tinnitus. AB - Subjective tinnitus is the perception of a sound without any external source. Repetitive transcranial magnetic stimulation (rTMS) has been examined as a treatment tool for chronic tinnitus for several years trying to target hyperactivity/abnormal synchronization within the auditory cortex putatively underlying the auditory phantom percept. However, its exact impact on auditory cortical activity remains largely unknown. This study's objective was to systematically examine changes in auditory responses (N1, auditory steady-state response [aSSR]) measured by means of magnetoencephalography after single sessions of stimulation with different TMS paradigms. Subjects with chronic tinnitus (n = 10) underwent five sessions of rTMS in which they received one of five different stimulation protocols (1 Hz, individual alpha frequency, continuous theta burst stimulation [cTBS], intermittent theta burst stimulation [iTBS], and sham) in randomized order using a single-blind study design. Cortical steady-state responses to 40 Hz amplitude-modulated tones were measured before and after each magnetic stimulation protocol. The results demonstrate a reduction of the cortical response to the auditory steady-state stimulus after magnetic stimulation, whereas the N1 response was slightly enhanced or remained unchanged. Furthermore, reduction of the aSSR was driven by effects of iTBS, cTBS, and 1 Hz stimulation. Correspondingly, behavioral measures demonstrated the greatest reduction of tinnitus loudness after the respective rTMS protocols. The current study offers an interesting insight into the effects of rTMS on auditory cortical activity. The results of the study are discussed in the context of current limitations of TMS for the treatment of chronic tinnitus. PMID- 20592126 TI - Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents. AB - To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents. PMID- 20592127 TI - Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy. AB - OBJECTIVE: A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy. DESIGN: Prospective study of GHD patients evaluated before and during short- (1 year, n=100) and long-term (5 years, n=50) rhGH therapy. METHODS: Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant. RESULTS: The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low density lipoprotein cholesterol was also observed. CONCLUSION: The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults. PMID- 20592128 TI - GH in combination with bisphosphonate treatment in osteogenesis imperfecta. AB - OBJECTIVE: To verify the effects of bisphosphonates (Bps) in combination with recombinant human GH (rGH) in pediatric osteogenesis imperfecta (OI) patients; we focused on possible improvement of bone mineral density (BMD), projected bone areas, growth velocity, and fractures risk. DESIGN: A randomized controlled 1 year clinical trial on 30 prepubertal children (M:F=14:16) affected by OI (type I, IV, and III) being treated with neridronate. METHODS: Following an observational period of 12 months during ongoing neridronate treatment, the patients were randomly divided into two groups: 15 were treated for 12 months with rGH and neridronate (group Bp+rGH) and 15 continued neridronate alone (group Bp). We evaluated auxological parameters, number of fractures, bone age (BA), bone metabolic parameters, and bone mass measurements (at lumbar spine and radius by dual-energy X-ray absorptiometry). RESULTS: The mean variation in percentage of BMD (Delta%BMD)--at lumbar spine (L2-L4), at distal and ultradistal radius- and the projected area of lumbar spine increased significantly in group Bp+rGH (P<0.05). Growth velocity was significantly higher during rGH treatment in group Bp+rGH versus group Bp and versus pretreatment (P<0.05), with no difference in increase in BA or fracture risk rate. Patients with quantitative (-qt) collagen synthesis defects had a higher, although not significant, response to rGH in terms of growth velocity and BMD. CONCLUSIONS: In OI patients, the combined rGH Bp treatment may give better results than Bp treatment alone, in terms of BMD, lumbar spine projected area and growth velocity, particularly in patients with quantitative defects. PMID- 20592129 TI - Half-baked? B vitamins and depression. PMID- 20592130 TI - A new twist on an old vitamin: human polymorphisms in the gene encoding the sodium-dependent vitamin C transporter 1. PMID- 20592131 TI - Meat consumption and prospective weight change in participants of the EPIC PANACEA study. AB - BACKGROUND: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION: Our results suggest that a decrease in meat consumption may improve weight management. PMID- 20592132 TI - Early rapid growth: no association with later cognitive functions in children born not small for gestational age. AB - BACKGROUND: There is an association between rapid growth in early life and overweight in childhood. This adverse association needs to be balanced against potential beneficial effects on cognitive functioning observed in children who are born small for gestational age (SGA). OBJECTIVE: We examined potential beneficial effects of rapid growth on cognitive functions in non-SGA children. DESIGN: We performed a systematic literature search of 3 databases. In addition, we analyzed data from the Avon Longitudinal Study on Parents and Children (ALSPAC). The association of rapid weight or length gain (defined as an increase of gt 0.67 in the SD score of weight or length between birth and the age of 25 mo) on intelligence quotient (IQ) measurements at 49 mo and 8 y (n = 836 and n = 701, respectively) was assessed in linear models adjusted for potential confounders. RESULTS: We identified 14 studies that assessed associations between any kind of early weight gain and cognitive outcome and that included non-SGA children. No study explicitly examined the effect of rapid weight gain. In the ALSPAC data, there was no positive association between rapid weight gain and IQ scores at either 49 mo [effect estimate (95% CI): minus 1.4 ( minus 3.6, 0.7)] or 8 y [ minus 0.8 ( minus 3.4, 1.9)] in non-SGA children. Subgroup analyses with stratification by sex of the children yielded similar results, as did analyses with rapid length gain. Supplementary analyses showed no linear association between weight gain and IQ. CONCLUSION: We showed no evidence that proposed adverse effects of rapid growth regarding later overweight will be counterbalanced by beneficial effects on cognitive functions in non-SGA children. PMID- 20592133 TI - Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women. AB - BACKGROUND: Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain. Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed. OBJECTIVE: We examined the association between intakes of sugar-sweetened and artificially sweetened soft drinks and preterm delivery. DESIGN: We conducted prospective cohort analyses of 59,334 women from the Danish National Birth Cohort (1996 2002). Soft drink intake was assessed in midpregnancy by using a food-frequency questionnaire. Preterm delivery ( lt 37 wk) was the primary outcome measure. Covariate information was assessed by telephone interviews. RESULTS: There was an association between intake of artificially sweetened carbonated and noncarbonated soft drinks and an increased risk of preterm delivery (P for trend: le 0.001, both variables). In comparison with women with no intake of artificially sweetened carbonated soft drinks, the adjusted odds ratio for women who consumed ge 1 serving of artificially sweetened carbonated soft drinks/d was 1.38 (95% CI: 1.15, 1.65). The corresponding odds ratio for women who consumed ge 4 servings of artificially sweetened carbonated soft drinks/d was 1.78 (95% CI: 1.19, 2.66). The association was observed for normal-weight and overweight women. A stronger increase in risk was observed for early preterm and moderately preterm delivery than with late-preterm delivery. No association was observed for sugar-sweetened carbonated soft drinks (P for trend: 0.29) or for sugar-sweetened noncarbonated soft drinks (P for trend: 0.93). CONCLUSIONS: Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery. Further studies are needed to reject or confirm these findings. PMID- 20592134 TI - Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study. AB - BACKGROUND: Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. OBJECTIVE: We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. DESIGN: We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. RESULTS: Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. CONCLUSIONS: In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations. PMID- 20592135 TI - Efficient silkworm expression of single-chain variable fragment antibody against ginsenoside Re using Bombyx mori nucleopolyhedrovirus bacmid DNA system and its application in enzyme-linked immunosorbent assay for quality control of total ginsenosides. AB - A single-chain variable fragment (scFv) antibody against ginsenoside Re (G-Re) have been successfully expressed in the silkworm larvae using Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA system. The baculovirus donor vector for expression of scFv against G-Re (GRe-scFv) was constructed to contain honeybee melittin signal sequence to accelerate secretion of the recombinant GRe-scFv into the haemolymph of silkworm larvae. Functional recombinant GRe-scFv was purified by cation exchange chromatography followed by immobilized metal ion affinity chromatography. The yield of purified GRe-scFv was 6.5 mg per 13 silkworm larvae, which is equivalent to 650 mg/l of the haemolymph, exhibiting extremely higher yield than that expressed in Escherichia coli (1.7 mg/l of culture medium). It was revealed from characterization that GRe-scFv retained similar characteristic of the parental monoclonal antibody (MAb) against G-Re (MAb-4G10), making it possible to develop indirect competitive enzyme-linked immunosorbent assay (icELISA) for quality control of total ginsenosides in various ginsengs. The detectable range for calibration of G-Re by developed icELISA shows 0.05-10 microg/ml. These results clearly suggested that the silkworm expression system is quite useful for the expression of functional scFv that frequently required time- and cost-consuming re-folding when it expressed in E. coli. PMID- 20592136 TI - Epidemiology and genetic characterization of hepatitis A virus genotype IIA. AB - Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5' untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored. PMID- 20592137 TI - Real-time PCR assay provides reliable assessment of intrapartum carriage of group B Streptococcus. AB - The objective of this study was to determine the reliability of the real-time PCR assay for determining the group B Streptococcus (GBS) status of women in labor. In this prospective study we compared the results of culture and PCR testing of vaginal and rectal samples collected by nursing staff when women were in labor. Patients' charts were also reviewed to obtain relevant information about pregnancy risk factors. Our results demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 90.5%, 96.1%, 86.4%, and 97.4%, respectively, for rapid PCR. Of the 196 women evaluated, 29 (14.8%) presented with unknown GBS status, 11 (37.9%) of whom received unnecessary intrapartum antibiotics. The rapid real-time PCR test was robust and was able to reliably detect the presence of GBS in women in labor within 1 h of specimen submission to the laboratory. We recommend that the rapid PCR test be targeted to women who present in labor with unknown GBS status. In cases where the laboratory does not offer 24-h availability of testing, sample collection followed by PCR testing the next morning is still valuable and provides reliable results 24 to 48 h faster than culture and will aid appropriate decision-making regarding continuing or stopping antibiotics for neonates of women with unknown GBS status. PMID- 20592138 TI - False-positive transcription-mediated amplification assay detection of West Nile virus in blood from a patient with viremia caused by an Usutu virus infection. AB - Detection of West Nile virus (WNV) by nucleic acid amplification technology (NAAT) is used widely to screen blood and organ donations in areas where WNV is endemic. We report a false-positive result of a WNV transcription-mediated amplification assay (TMA) in a patient with viremia that was caused by Usutu virus, a mosquito-borne flavivirus. PMID- 20592139 TI - Chlamydophila psittaci zoonotic risk assessment in a chicken and turkey slaughterhouse. AB - Chlamydophila psittaci causes respiratory disease in poultry and can be transmitted to humans. We conducted a C. psittaci zoonotic risk assessment study of a chicken and turkey slaughterhouse. Eighty-five percent of the slaughtered chicken flocks tested positive by PCR and culture. Genotype D was discovered. Fifty-seven percent of the slaughtered turkey flocks tested positive by PCR and culture. Genotype D was present. For the chicken slaughterhouse employees, 7.5% and 6% tested positive for C. psittaci by PCR and culture, respectively. In the turkey slaughterhouse, 87% and 61% of the employees tested positive by PCR and culture, respectively. All genotyped human samples contained genotype D. Using stationary bioaerosol monitoring by means of an MAS-100 ecosampler and ChlamyTrap collection medium, chlamydial DNA, and viable organisms were detected in both the chicken and turkey slaughterhouses. Positive air samples were most frequently found in the animal reception area and evisceration room. Zoonotic transmissions were very common, especially from processed turkeys. Accurate diagnostic monitoring and reporting of C. psittaci infections should be promoted in poultry workers. PMID- 20592140 TI - Lack of evidence for the presence of mosquito-borne arboviruses in the upper Rhine Valley, Germany, in 1999 to 2000. PMID- 20592141 TI - Performance of the Aptima HIV-1 RNA qualitative assay with 16- and 32-member specimen pools. AB - The Aptima HIV-1 RNA qualitative assay tested with a WHO-approved HIV type 1 RNA standard in 16- and 32-member pools detected 100% of the pools (1,070 and 2,130 HIV-1 RNA copies/ml/pool, respectively), thus exceeding the FDA-required lower limit of detection. The Aptima test can be used to screen for acute-phase HIV infection. PMID- 20592142 TI - Leukoencephalopathy associated with parvovirus infection in Cretan hound puppies. AB - Leukoencephalopathies in dogs encompass presumably inherited conditions such as leukodystrophies, hypomyelination or spongiform degeneration, but other causes, such as virus infections and toxic or nutritional factors, might also play a contributory role. In this report, we provide evidence of parvovirus infection and replication in the brains of five 6-week-old Cretan hound puppies suffering from a puppy shaker syndrome and leukoencephalopathy. Although these puppies belonged to two different litters, they were closely related, tracing back two generations to the same sire. Histologically, a mild to moderate lymphohistiocytic meningitis, with focal lymphohistiocytic leukoencephalitis in two animals, and a mild to moderate vacuolation with myelin loss, mainly in the white matter of the cerebellum was detected. Vacuolation was also found in the corpus callosum, fimbria hippocampi, mesencephalon, capsula interna, basal ganglia, and hypothalamus. By immunohistology and in situ hybridization, either parvoviral antigen, DNA, mRNA, or replicative intermediate DNA were detected in the cerebellum, hippocampus, periventricular areas, corpus callosum, cerebral cortex, medulla oblongata, and spinal cord. Parvovirus antigen, DNA, and mRNA were present in cells of the outer granular layer of the cerebellum and in periventricular cells, most likely representing spongioblasts, glial cells, neurons, endothelial cells, occasional macrophages, and ependymal cells. Sequencing revealed canine parvovirus type 2 stretches. Thus, an association of parvovirus infection with the leukoencephalopathy seems likely, possibly facilitated by a genetic predisposition due to the mode of inbreeding in this particular dog breed. PMID- 20592143 TI - High-resolution typing by integration of genome sequencing data in a large tuberculosis cluster. AB - To investigate whether genome sequencing yields more useful markers than those currently used to study the epidemiology of tuberculosis, it was applied to three Mycobacterium tuberculosis isolates of the Harlingen outbreak. Our findings suggest that single nucleotide polymorphisms can be used to identify transmission chains in restriction fragment length polymorphism clusters. PMID- 20592144 TI - Coxiella burnetii infection of a Steller sea lion (Eumetopias jubatus) found in Washington State. AB - A pregnant sea lion stranded in the State of Washington was found to have placentitis caused by a unique strain of Coxiella burnetii. This is the first description of coxiellosis in a sea lion and suggests that exposure to sea lions may be a risk factor for contracting Q fever. PMID- 20592145 TI - Emergence of VIM-12 in Enterobacter cloacae. AB - Detection of the bla(VIM-12) gene within the originally described Inh12 integron in a clinical isolate of Enterobacter cloacae is reported for the first time worldwide. Integron Inh12 was carried on a conjugative plasmid of approximately 85 kb which also conferred resistance to aztreonam, likely due to AmpC production. PMID- 20592146 TI - Multiplex PCR for differential identification of broad tapeworms (Cestoda: Diphyllobothrium) infecting humans. AB - The specific identification of broad tapeworms (genus Diphyllobothrium) infecting humans is very difficult to perform by morphological observation. Molecular analysis by PCR and sequencing represents the only reliable tool to date to identify these parasites to the species level. Due to the recent spread of human diphyllobothriosis in several countries, a correct diagnosis has become crucial to better understand the distribution and the life cycle of human-infecting species as well as to prevent the introduction of parasites to disease-free water systems. Nevertheless, PCR and sequencing, although highly precise, are too complicated, long, and expensive to be employed in medical laboratories for routine diagnostics. In the present study we optimized a cheap and rapid molecular test for the differential identification of the most common Diphyllobothrium species infecting humans (D. latum, D. dendriticum, D. nihonkaiense, and D. pacificum), based on a multiplex PCR with the cytochrome c oxidase subunit 1 gene of mitochondrial DNA. PMID- 20592147 TI - Frequency of detection of upper respiratory tract viruses in patients tested for pandemic H1N1/09 viral infection. AB - Molecular testing of 270 consecutive nasopharyngeal swab samples taken in May and June 2009 and 274 samples from patients hospitalized between July and December 2009 showed similar findings of respiratory viruses, with influenza A pandemic virus H1N1/09 being the most represented, followed by human parainfluenza virus type 3 and rhinoviruses. Statistical analyses suggested virus cocirculation in the absence of viral interference. PMID- 20592148 TI - Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman native to Afghanistan. AB - Rhinocladiella mackenziei is a recognized cause of endemic cerebral phaeohyphomycosis in the Middle East area. Surgical resection of the abscesses and posaconazole treatment have improved the ominous prognosis of this disease. We describe the case of a native Afghan woman living in France who presented with brain abscesses due to R. mackenziei. PMID- 20592149 TI - Comparison of broth microdilution, agar dilution, and Etest for susceptibility testing of doripenem against gram-negative and gram-positive pathogens. AB - The susceptibility of 513 clinical isolates to doripenem was determined by broth microdilution, agar dilution, and Etest. Overall agreements for Etest and agar dilution MIC values compared to reference broth microdilution at +/-1 log(2) dilution were 88% and 94%, respectively. Etest MIC values demonstrated 98% agreement within +/-2 log(2) dilutions compared to the reference broth microdilution method. PMID- 20592150 TI - Rapid detection and identification of mucormycetes from culture and tissue samples by use of high-resolution melt analysis. AB - We present a method for rapid and simple detection of clinically relevant mucormycetes of the Mucorales order in cultures and clinical samples. This seminested real-time PCR uses mucormycete-specific primers and is followed by species identification using high-resolution melt (HRM) analysis. The method is highly suitable for routine clinical diagnostics. PMID- 20592151 TI - Axillary abscess complicated by venous thrombosis: identification of Streptococcus pyogenes by 16S PCR. AB - We report a case of an axillary abscess with Streptococcus pyogenes complicated by venous thrombosis. Bacterial etiology and typing were obtained by PCR and sequencing of the 16S rRNA and M-protein genes from abscess material. The bacterium was of serotype M41, and serology indicated that it had expressed procoagulant factors. PMID- 20592152 TI - Incidence, characteristics, and outcomes of Staphylococcus lugdunensis bacteremia. AB - Of 63 patients with Staphylococcus lugdunensis bacteremia, 15 (23.8%) had clinically significant bacteremia, with an incidence of 1.3 cases per 100,000 admissions. Of the five patients with community-acquired S. lugdunensis bacteremia, three had endocarditis. Catheters were the most common portal of entry for health-care-associated or hospital-acquired bacteremia. Only one patient died of bacteremia-related causes. PMID- 20592153 TI - Broad-range 16S rRNA PCR with cerebrospinal fluid may be unreliable for management of postoperative aseptic meningitis. AB - We previously demonstrated that discontinuing presumptive antibiotic treatment in cases of negative conventional cultures is safe and effective for patients with postoperative aseptic meningitis (PAM). Here, we prospectively investigated 32 patients with postoperative meningitis. All 26 patients with PAM diagnosed on the basis of conventional cultures demonstrated negative 16S rRNA PCR results. Our results suggest that the PCR technique does not change PAM management. PMID- 20592154 TI - Evaluation of a chromogenic agar for detection of group B streptococcus in pregnant women. AB - We compared ChromID Strepto B agar (STRB; bioMerieux, Inc.), a selective and differential medium for group B streptococcus, with culture using neomycin nalidixic acid agar (NNA) and LIM broth. STRB alone was more sensitive (87.7%) than NNA alone (79.0%), while each had a sensitivity of 100% when used in conjunction with LIM broth. PMID- 20592155 TI - Development of a skin test for bovine tuberculosis for differentiating infected from vaccinated animals. AB - The tuberculin skin test has been used for the diagnosis of bovine and human tuberculosis (TB) for over a hundred years. However, the specificity of the test is compromised by vaccination with the Mycobacterium bovis-derived vaccine strain bacille Calmette-Guerin (BCG). Since current promising vaccines against bovine TB are based on heterologous prime-boost combinations that include BCG, there is a need for diagnostic tests for differentiating infected from vaccinated animals (DIVA). The application of antigens such as ESAT-6 and CFP-10 for DIVA has so far been realized largely through their application in the blood-based gamma interferon release assay. In the current study, we have reassessed the potential of such antigens as skin test reagents for DIVA in cattle. A cocktail of the Mycobacterium tuberculosis complex recombinant protein antigens ESAT-6, CFP-10, MPB70, and MPB83 elicited delayed-type hypersensitivity (DTH) skin test responses in 78% of naturally infected tuberculin-positive cattle. Importantly, this cocktail induced no skin responses in BCG-vaccinated cattle despite them being sensitized for strong tuberculin responses. Further optimization of skin test antigen combinations identified that the inclusion of Rv3615c (Mb3645c) enhanced skin test sensitivity in naturally infected cattle without compromising specificity. In addition, we demonstrate for the first time the utility of synthetic peptides as promising skin test antigens for bovine TB for DIVA. Our data provide a promising basis for the future development of skin tests for DIVA with practical relevance for TB diagnosis in both veterinary and clinical settings. PMID- 20592156 TI - Evaluation of one- and two-color gene expression arrays for microbial comparative genome hybridization analyses in routine applications. AB - DNA microarray technology has already revolutionized basic research in infectious diseases, and whole-genome sequencing efforts have allowed for the fabrication of tailor-made spotted microarrays for an increasing number of bacterial pathogens. However, the application of microarrays in diagnostic microbiology is currently hampered by the high costs associated with microarray experiments and the specialized equipment needed. Here, we show that a thorough bioinformatic postprocessing of the microarray design to reduce the amount of unspecific noise also allows the reliable use of spotted gene expression microarrays for gene content analyses. We further demonstrate that the use of only single-color labeling to halve the costs for dye-labeled nucleotides results in only a moderate decrease in overall specificity and sensitivity. Therefore, gene expression microarrays using only single-color labeling can also reliably be used for gene content analyses, thus reducing the costs for potential routine applications such as genome-based pathogen detection or strain typing. PMID- 20592157 TI - Screening of urine samples by flow cytometry reduces the need for culture. AB - Urine samples constitute a large proportion of samples tested in clinical microbiology laboratories. Culturing of the samples is fairly time- and labor consuming, and most of the samples will yield no growth or insignificant growth. We analyzed the feasibility of the flow cytometry-based UF-500i instrument (Sysmex, Japan) to screen out urine samples with no growth or insignificant growth and reduce the number of samples to be cultured. A total of 1,094 urine specimens sent to our laboratory for culture during 4 months in the spring of 2009 in Lahti, Finland, were included in the study. After culture, all samples were analyzed with the Sysmex UF-500i for bacterial and leukocyte (white blood cell [WBC]) counts. Youden index and closest (0,1) methods were used to determine the cutoff values for bacterial and WBC counts in culture-positive and -negative groups. By flow cytometry, samples considered positive for UTI in culture had bacterial and WBC values that were significantly higher than those for samples considered negative. The flow cytometric screening worked best when both bacterial counts and WBC counts were used with age- and gender-specific cutoff values for all patient groups, excluding patients with urological disease or anomaly. By use of these cutoff values, 5/167 (3.0%) of culture-positive samples were missed by UF-500i and the percentage of samples that did not need to be cultured was 64.5%. Use of the UF-500i instrument is a reliable method for screening out a major part of the UTI-negative samples, significantly diminishing the amount of work required in the microbiology laboratory. PMID- 20592158 TI - Candidemia surveillance in Brazil: evidence for a geographical boundary defining an area exhibiting an abatement of infections by Candida albicans group 2 strains. AB - Prospective population surveillance has been conducted for candidemia in Brazil (A. L. Colombo, M. Nucci, B. J. Park, et al., J. Clin. Microbiol. 44:2816-2823, 2006). In the present study, a total of 63 isolates from 61 patients, representing 11 medical centers from nine geographic regions, were characterized by multilocus sequence typing (MLST). A total of 48 unique profiles or diploid sequence types (DSTs) were observed, with nine new sequence types (STs) and 32 new DSTs. There were no apparent correlations between center/region and DST patterns. Subtypes were compared to those in a known characterized reference set, including a large database of strains obtained worldwide. Significantly, only one C. albicans group 2 isolate was found in our collection, although isolates from this particular group are commonly found worldwide. These data, combined with information from other previously reported studies, establish a statistically significant diminishment of group 2 strains in Central and South America, including Mexico and portions of the Southwestern United States. PMID- 20592159 TI - Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). AB - Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined in order to establish epidemiologic cutoff values (ECVs) for five Aspergillus spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for Aspergillus fumigatus. The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for A. fumigatus, 323 to 592 for A. flavus, 131 to 143 for A. nidulans, 366 to 520 for A. niger, 330 to 462 for A. terreus, and 45 to 84 for A. versicolor. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in microg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses): A. fumigatus, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%); A. flavus, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%); A. nidulans, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%); A. niger, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%); A. terreus, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%); A. versicolor, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to cyp51A mutations, a resistance mechanism in some Aspergillus spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision. PMID- 20592160 TI - Glucagon deficiency reduces hepatic glucose production and improves glucose tolerance in adult mice. AB - The major role of glucagon is to promote hepatic gluconeogenesis and glycogenolysis to raise blood glucose levels during hypoglycemic conditions. Several animal models have been established to examine the in vivo function of glucagon in the liver through attenuation of glucagon via glucagon receptor knockout animals and pharmacological interventions. To investigate the consequences of glucagon loss to hepatic glucose production and glucose homeostasis, we derived mice with a pancreas specific ablation of the alpha-cell transcription factor, Arx, resulting in a complete loss of the glucagon-producing pancreatic alpha-cell. Using this model, we found that glucagon is not required for the general health of mice but is essential for total hepatic glucose production. Our data clarifies the importance of glucagon during the regulation of fasting and postprandial glucose homeostasis. PMID- 20592161 TI - Minireview: Switching on progesterone receptor expression with duplex RNA. AB - It has long been appreciated that gene expression is regulated by protein complexes at promoters. More recently, research has demonstrated that small duplex RNAs such as micro-RNAs and short interfering RNAs complementary to mRNA provide another layer of regulation. Evidence now supports the existence of regulatory pathways that use small duplex RNAs to control transcription. Synthetic RNAs complementary to gene promoters [antigene RNAs (agRNAs)] can either activate or inhibit gene expression. Activity of agRNAs is mediated by argonaute, a protein required for RNA interference. Unlike protein transcription factors, agRNAs do not bind to chromosomal DNA but recognize noncoding transcripts that overlap gene promoters or 3'-gene termini. This review describes recent studies with agRNAs and focuses on the robust and potent agRNA-mediated regulation of progesterone receptor. The ability of small RNAs to alter transcription provides a new layer of potential regulation for gene expression. PMID- 20592163 TI - 55-Year-old man with thunderclap headache. PMID- 20592162 TI - Research resource: Gonadotropin-releasing hormone receptor-mediated signaling network in LbetaT2 cells: a pathway-based web-accessible knowledgebase. AB - The GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LbetaT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators. In order to facilitate access to the information contained in this complex and evolving literature, we have developed a pathway based knowledgebase that is web hosted. At present, using 106 relevant primary publications, we curated a comprehensive knowledgebase of the GnRHR signaling in the LbetaT2 cell in the form of a process diagram. Positive and negative controls of gonadotropin gene expression, which included GnRH itself, hypothalamic factors, gonadal steroids and peptides, as well as other hormones, were illustrated. The knowledgebase contains 187 entities and 206 reactions. It was assembled using CellDesigner software, which provides an annotated graphic representation of interactions, stored in Systems Biology Mark-up Language. We then utilized Biological Pathway Publisher, a software suite previously developed in our laboratory, to host the knowledgebase in a web-accessible format as a public resource. In addition, the network entities were linked to a public wiki, providing a forum for discussion, updating, and error correction. The GnRHR signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html. PMID- 20592164 TI - Edward L. Trudeau--founder of a sanatorium for treatment of tuberculosis. PMID- 20592168 TI - Body composition and heart failure prevalence and prognosis: getting to the fat of the matter in the "obesity paradox". PMID- 20592169 TI - Association between direct measures of body composition and prognostic factors in chronic heart failure. AB - OBJECTIVE: To explore the covariate-adjusted associations between body composition (percent body fat and lean body mass) and prognostic factors for mortality in patients with chronic heart failure (CHF) (nutritional status, N terminal pro-B-type natriuretic peptide [NT-proBNP], quality of life, exercise capacity, and C-reactive protein). PATIENTS AND METHODS: Between June 2008 and July 2009, we directly measured body composition using dual energy x-ray absorptiometry in 140 patients with systolic and/or diastolic heart failure. We compared body composition and CHF prognostic factors across body fat reference ranges and body mass index (BMI) categories. Multiple linear regression models were created to examine the independent associations between body composition and CHF prognostic factors; we contrasted these with models that used BMI. RESULTS: Use of BMI misclassified body fat status in 51 patients (41%). Body mass index was correlated with both lean body mass (r=0.72) and percent body fat (r=0.67). Lean body mass significantly increased with increasing BMI but not with percent body fat. Body mass index was significantly associated with lower NT-proBNP and lower exercise capacity. In contrast, higher percent body fat was associated with a higher serum prealbumin level, lower exercise capacity, and increased C reactive protein level; lean body mass was inversely associated with NT-proBNP and positively associated with hand-grip strength. CONCLUSION: When BMI is divided into fat and lean mass components, a higher lean body mass and/or lower fat mass is independently associated with factors that are prognostically advantageous in CHF. Body mass index may not be a good indicator of adiposity and may in fact be a better surrogate for lean body mass in this population. PMID- 20592170 TI - Intraoperative echocardiography in valvular heart disease: an evidence-based appraisal. AB - Intraoperative (IO) transesophageal echocardiography (TEE) is widely used for assessing the results of valvular heart disease (VHD) surgery. Epiaortic ultrasonography (EAU) has been recommended for prevention of perioperative strokes. To what extent does high-quality evidence justify the widespread use of these imaging modalities? In March 2009, we searched MEDLINE (PubMed and OVID interfaces) and EMBASE for studies published in English using database-specific controlled vocabulary describing the concepts of IOTEE, cardiac surgery, VHD, and EAU. We found no randomized trials or studies with control groups assessing the impact of IOTEE in VHD surgery. Pooled analysis of 8 observational studies including 15,540 patients showed an average incidence of 11% for prebypass surgical changes and 4% for second pump runs, suggesting that patients undergoing VHD surgery may benefit significantly from IOTEE, particularly from postcardiopulmonary bypass IOTEE in aortic repair and mitral repair and replacement, but less so in isolated aortic replacement. Further available indirect evidence was satisfactory in the test accuracy and surgical quality control aspects, with low complication rates for IOTEE. The data supporting EAU included 12,687 patients in 2 prospective randomized studies and 4 nonrandomized, controlled studies, producing inconsistent outcome-related results. Despite low quality scientific evidence supporting IOTEE in VHD surgery, we conclude that indirect evidence supporting its use is satisfactory and suggests that IOTEE may offer considerable benefit in valvular repairs and mitral replacements. The value of IOTEE in isolated aortic valve replacement remains less clear. Evidence supporting EAU is scientifically more robust but conflicting. These findings have important clinical policy and research implications. PMID- 20592172 TI - Clinical pearls in men's health. PMID- 20592171 TI - Cancer-associated myeloproliferation: old association, new therapeutic target. AB - The association between malignancy and development of a paraneoplastic leukocytosis, the so-called leukemoid reaction, has long been appreciated. Although a leukemoid reaction has conventionally been defined as a peripheral blood leukocytosis composed of both mature and immature granulocytes that exceeds 50,000/microL, a less profound leukocytosis may be appreciated in many patients harboring a malignant disease. More recent insights have shed new light on this long-recognized association, because research performed in both murine models and cancer patients has uncovered multiple mechanisms by which tumors both drive myelopoiesis, sometimes leading to a clinically apparent leukocytosis, and inhibit the differentiation of myeloid cells, resulting in a qualitative change in myelopoiesis. This qualitative change leads to the accumulation of immature myeloid cells, which due to their immune suppressive effects have been collectively called myeloid-derived suppressor cells. More recently, myeloid cells have been shown to promote tumor angiogenesis. Cancer-associated myeloproliferation is not merely a paraneoplastic phenomenon of questionable importance but leads to the suppression of host immunity and promotion of tumor angiogenesis, both of which play an integral part in tumorigenesis and metastasis. Therefore, cancer-associated myeloproliferation represents a novel therapeutic target in cancer that, decades after its recognition, is only now being translated into clinical practice. PMID- 20592173 TI - 38-year old woman with hypertension, headaches, and abdominal bruit. PMID- 20592175 TI - Does thermal therapy benefit patients with chronic heart failure? PMID- 20592174 TI - Peripheral artery disease: current insight into the disease and its diagnosis and management. AB - Peripheral artery disease (PAD), which comprises atherosclerosis of the abdominal aorta, iliac, and lower-extremity arteries, is underdiagnosed, undertreated, and poorly understood by the medical community. Patients with PAD may experience a multitude of problems, such as claudication, ischemic rest pain, ischemic ulcerations, repeated hospitalizations, revascularizations, and limb loss. This may lead to a poor quality of life and a high rate of depression. From the standpoint of the limb, the prognosis of patients with PAD is favorable in that the claudication remains stable in 70% to 80% of patients over a 10-year period. However, the rate of myocardial infarction, stroke, and cardiovascular death in patients with both symptomatic and asymptomatic PAD is markedly increased. The ankle brachial index is an excellent screening test for the presence of PAD. Imaging studies (duplex ultrasonography, computed tomographic angiography, magnetic resonance angiography, catheter-based angiography) may provide additional anatomic information if revascularization is planned. The goals of therapy are to improve symptoms and thus quality of life and to decrease the cardiovascular event rate (myocardial infarction, stroke, cardiovascular death). The former is accomplished by establishing a supervised exercise program and administering cilostazol or performing a revascularization procedure if medical therapy is ineffective. A comprehensive program of cardiovascular risk modification (discontinuation of tobacco use and control of lipids, blood pressure, and diabetes) will help to prevent the latter. PMID- 20592176 TI - Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase. AB - To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein (Dbp), in skeletal muscle (H/L: 10.7 +/- 3.7 at 3 h vs. 2.2 +/- 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 +/- 0.5 at 0 h) vs. unsplit hamsters (1.2 +/- 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (psi(me)) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators. PMID- 20592177 TI - Absence of mitochondrial activation during levosimendan inotropic action in perfused paced guinea pig hearts as demonstrated by modular control analysis. AB - Levosimendan is a calcium sensitizer developed for the treatment of heart failure. It increases contractile force by enhancing the sensitivity of myofilaments to calcium. Besides this sensitizing effect, the drug has also been reported to show some inhibitory action on phosphodiesterase 3 (PDE3). The inotropic effects of levosimendan have been studied on guinea pig paced perfused hearts by using modular control analysis (MoCA) (Diolez P, Deschodt-Arsac V, Raffard G, Simon C, Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp Physiol 293: R13-R19, 2007.), an integrative approach of heart energetics using noninvasive (31)P NMR. The aim was to evaluate quantitatively the respective effects of this drug on energy supply and demand modules. Under our experimental conditions, 0.7 muM levosimendan induced a 45% increase in paced heart output associated with a 7% decrease in phosphocreatine and a negligible increase in oxygen consumption. Because MoCA allows in situ study of the internal regulations in intact beating heart energetics, it was applied to describe quantitatively by which routes levosimendan exerts its inotropic action. MoCA demonstrated the absence of any significant effect of the drug on the supply module, which is responsible for the lower increase in oxygen consumption, compared with epinephrine, which increases the ratio between myocardial oxygen consumption and cardiac contraction. This result evidences that, under our conditions, a possible effect of levosimendan on PDE3 activity and/or intracellular calcium remains very low on mitochondrial activity and insignificant on integrated cardiac energetics. Thus, levosimendan inotropic effect on guinea pig heart depends almost entirely on the calcium-sensitizing properties leading to myofilament activation and the concomitant activation of energy supply by the decrease in PCr, therefore improving energetic efficiency of contraction. PMID- 20592178 TI - Acute daily psychological stress causes increased atrophic gene expression and myostatin-dependent muscle atrophy. AB - Psychological stress is known to attenuate body size and lean body mass. We tested the effects of 1, 3, or 7 days of two different models of psychological stress, 1 h of daily restraint stress (RS) or daily cage-switching stress (CS), on skeletal muscle size and atrophy-associated gene expression in mice. Thymus weights decreased in both RS and CS mice compared with unstressed controls, suggesting that both models activated the hypothalamic-pituitary-adrenal axis. Body mass was significantly decreased at all time points for both models of stress but was greater for RS than CS. Mass of the tibialis anterior (TA) and soleus (SOL) muscles was significantly decreased after 3 and 7 days of RS, but CS only significantly decreased SOL mass after 7 days. TA mRNA levels of the atrophy associated genes myostatin (MSTN), atrogin-1, and the phosphatidylinositol 3 kinase inhibitory subunit p85alpha were all significantly increased relative to unstressed mice after 1 and 3 days of RS, and expression of MSTN and p85alpha mRNA remained elevated after 7 days of RS. Expression of muscle ring finger 1 was increased after 1 day of RS but returned to baseline at 3 and 7 days of RS. MSTN, atrogin-1, and p85alpha mRNA levels also significantly increased after 1 and 3 days of CS but atrogen-1 mRNA levels had resolved back to normal levels by 3 days and p85alpha with 7 days of CS. p21CIP mRNA levels were significantly decreased by 3 days of CS or RS. Finally, body mass was minimally affected, and muscle mass was completely unaffected by 3 days of RS in mice null for the MSTN gene, and MSTN inactivation attenuated the increase in atrogin-1 mRNA levels with 4 days of RS compared with wild-type mice. Together these data suggest that acute daily psychological stress induces atrophic gene expression and loss of muscle mass that appears to be MSTN dependent. PMID- 20592179 TI - Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction. AB - Following burn injury, the host is susceptible to bacterial infections normally cleared by healthy patients. We hypothesized that during the systemic immune response that follows scald injury, the host's altered immune status increases infection susceptibility. Using a murine model of scald injury under inhaled anesthesia followed by intraperitoneal infection, we observed increased neutrophil numbers and function at postburn day (PBD) 1 compared with sham-burned and PBD4 mice. Further, increased mortality, bacteremia, and serum IL-6 were observed in PBD1 mice after Pseudomonas aeruginosa (PA) infection compared with sham-burned and PBD4 mice infected with PA. To examine these disparate responses, we investigated neutrophils isolated at 5 and 24 h following PA infection from PBD1 and sham-burned mice. Five hours after infection, there was no significant difference in number of recruited neutrophils; however, neutrophils from injured mice had decreased activation, active-p38, and oxidative burst compared with sham burned mice. In direct contrast, 24 h after infection, we observed increased numbers, active-p38, and oxidative burst of neutrophils from PBD1 mice. Finally, we demonstrated that in neutrophils isolated from PBD1 mice, the observed increase in oxidative burst was p38 dependent. Altogether, neutrophil activation and function from thermally injured mice are initially delayed and later exacerbated by a p38-dependent mechanism. This mechanism is likely key to the observed increase in bacterial load and mortality of PBD1 mice infected with PA. PMID- 20592180 TI - Internalization of the opioid growth factor, [Met5]-enkephalin, is dependent on clathrin-mediated endocytosis for downregulation of cell proliferation. AB - The opioid growth factor (OGF; [Met(5)]-enkephalin), a constitutively expressed and tonically active inhibitory peptide, interacts with the OGF receptor (OGFr) to form an endogenous growth-regulating pathway in homeostasis. Amplification of OGF-OGFr interfacing in animal and clinical studies depresses development, neoplasia, angiogenesis, and immunity. Disruption of the OGF-OGFr axis accelerates cell proliferation and has been particularly important in wound repair. To investigate how OGF enters cells, OGF was labeled with 5,6 tetramethylrhodamine OGF (RhoOGF) to study its uptake in live cells. African green monkey kidney cells (COS-7) incubated with RhoOGF exhibited a temperature dependent course of entry, being internalized at 37 degrees C but not at 4 degrees C. RhoOGF was detected in the cytoplasm 15 min after initial exposure, observed in both cytoplasm and nucleus within 30 min, and remained in the cells for as long as 5 h. A 100-fold excess of OGF or the opioid antagonist naltrexone, but not other opioid ligands (some selective for classic opioid receptors), markedly reduced entry of RhoOGF into cells. RhoOGF was functional because DNA synthesis in cells incubated with RhoOGF (10(-5) to 10(-8) M) was decreased 24 36%, and was comparable to cells treated with unlabeled OGF (reductions of 26 39%). OGF internalization was dependent on clathrin-mediated endocytosis, with addition of clathrin siRNA diminishing the uptake of RhoOGF and upregulating DNA synthesis. RhoOGF clathrin-mediated endocytosis was unrelated to endosomal or Golgi pathways. Taken together, these results suggest that OGF enters cells by active transport in a saturable manner that requires clathrin-mediated endocytosis. PMID- 20592181 TI - The kindlins at a glance. PMID- 20592182 TI - Stem cells in cancer: instigators and propagators? AB - There is growing realization that many - if not all - cancer-cell populations contain a subpopulation of self-renewing stem cells known as cancer stem cells (CSCs). Unlike normal adult stem cells that remain constant in number, CSCs can increase in number as tumours grow, and give rise to progeny that can be both locally invasive and colonise distant sites - the two hallmarks of malignancy. Immunodeficient mouse models in which human tumours can be xenografted provide persuasive evidence that CSCs are present in human leukaemias and many types of solid tumour. In addition, many studies have found similar subpopulations in mouse tumours that show enhanced tumorigenic properties when they are transplanted into histocompatible mice. In this Commentary, we refer to CSCs as tumour-propagating cells (TPCs), a term that reflects the assays that are currently employed to identify them. We first discuss evidence that cancer can originate from normal stem cells or closely related descendants. We then outline the attributes of TPCs and review studies in which they have been identified in various cancers. Finally, we discuss the implications of these findings for successful cancer therapies. PMID- 20592183 TI - Temporal regulation of the muscle gene cascade by Macho1 and Tbx6 transcription factors in Ciona intestinalis. AB - For over a century, muscle formation in the ascidian embryo has been representative of 'mosaic' development. The molecular basis of muscle-fate predetermination has been partly elucidated with the discovery of Macho1, a maternal zinc-finger transcription factor necessary and sufficient for primary muscle development, and of its transcriptional intermediaries Tbx6b and Tbx6c. However, the molecular mechanisms by which the maternal information is decoded by cis-regulatory modules (CRMs) associated with muscle transcription factor and structural genes, and the ways by which a seamless transition from maternal to zygotic transcription is ensured, are still mostly unclear. By combining misexpression assays with CRM analyses, we have identified the mechanisms through which Ciona Macho1 (Ci-Macho1) initiates expression of Ci-Tbx6b and Ci-Tbx6c, and we have unveiled the cross-regulatory interactions between the latter transcription factors. Knowledge acquired from the analysis of the Ci-Tbx6b CRM facilitated both the identification of a related CRM in the Ci-Tbx6c locus and the characterization of two CRMs associated with the structural muscle gene fibrillar collagen 1 (CiFCol1). We use these representative examples to reconstruct how compact CRMs orchestrate the muscle developmental program from pre-localized ooplasmic determinants to differentiated larval muscle in ascidian embryos. PMID- 20592184 TI - Telomerase trafficking and assembly in Xenopus oocytes. AB - The core components of telomerase are telomerase RNA (TR) and telomerase reverse transcriptase (TERT). In vertebrate cells, TR and TERT have been reported to associate with intranuclear structures, including Cajal bodies and nucleoli as well as telomeres. Here, we examined the time course of both TR localization and assembly of TR with TERT in Xenopus oocytes. The major trafficking pathway for microinjected TR is through Cajal bodies into the nucleoplasm, with a fraction of TR found in nucleoli at later time points. Telomerase assembly precedes nucleolar localization of TR, and TR mutants that do not localize to nucleoli form active enzyme, indicating that localization of TR to nucleoli is not required for assembly with TERT. Assembly of telomerase coincides with Cajal-body localization; however, assembly is also unaffected by a CAB-box mutation (which significantly reduces association with Cajal bodies), suggesting that Cajal-body localization is not important for assembly. Our results suggest that assembly of TR with TERT occurs in the nucleoplasm. Unexpectedly, however, our experiments reveal that disruption of the CAB box does not eliminate early targeting to Cajal bodies, indicating that a role for Cajal bodies in telomerase assembly cannot be excluded on the basis of existing knowledge. PMID- 20592185 TI - Membrane assembly modulates the stability of the meiotic spindle-pole body. AB - Spore formation in Saccharomyces cerevisiae is driven by de novo assembly of new membranes termed prospore membranes. A vesicle-docking complex called the meiosis II outer plaque (MOP) forms on the cytoplasmic faces of the spindle-pole bodies at the onset of meiosis II and serves as the initiation site for membrane formation. In this study, a fluorescence-recovery assay was used to demonstrate that the dynamics of the MOP proteins change coincident with the coalescence of precursor vesicles into a membrane. Proteins within the MOP exchange freely with a soluble pool prior to membrane assembly, but after membranes are formed they remain stably within the MOP. By contrast, constitutive spindle-pole-body proteins display low exchange in both conditions. The MOP component Ady4p plays a role in maintaining the integrity of the MOP complex, but this role differs depending on whether the MOP is associated with docked vesicles or a fully formed membrane. These results suggest an architectural rearrangement of the MOP coincident with vesicle fusion. PMID- 20592186 TI - alpha2beta1 integrin controls association of Rac with the membrane and triggers quiescence of endothelial cells. AB - Integrin receptors and their extracellular matrix ligands provide cues to cell proliferation, survival, differentiation and migration. Here, we show that alpha2beta1 integrin, when ligated to the basement membrane component laminin-1, triggers a proliferation arrest in primary endothelial cells. Indeed, in the presence of strong growth signals supplied by growth factors and fibronectin, alpha2beta1 engagement alters assembly of mature focal adhesions by alpha5beta1 and leads to impairment of downstream signaling and cell-cycle arrest in the G1 phase. Although the capacity of alpha5beta1 to signal for GTP loading of Rac is preserved, the joint engagement of alpha2beta1 interferes with membrane anchorage of Rac. Adapting the 'split-ubiquitin' sensor to screen for membrane-proximal alpha2 integrin partners, we identified the CD9 tetraspanin and further establish its requirement for destabilization of focal adhesions, control of Rac subcellular localization and growth arrest induced by alpha2beta1 integrin. Altogether, our data establish that alpha2beta1 integrin controls endothelial cell commitment towards quiescence by triggering a CD9-dependent dominant signaling. PMID- 20592187 TI - Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral sorting signal. AB - The P2Y(1) receptor is localized to the basolateral membrane of polarized Madin Darby canine kidney (MDCK) cells. In the present study, we identified a 25 residue region within the C-terminal tail (C-tail) of the P2Y(1) receptor that directs basolateral sorting. Deletion of this sorting signal caused redirection of the receptor to the apical membrane, indicating that the region from the N terminus to transmembrane domain 7 (TM7) contains an apical-sorting signal that is overridden by a dominant basolateral signal in the C-tail. Location of the signal relative to TM7 is crucial, because increasing its distance from the end of TM7 resulted in loss of basolateral sorting. The basolateral-sorting signal does not use any previously established basolateral-sorting motifs, i.e. tyrosine containing or di-hydrophobic motifs, for function, and it is functional even when inverted or when its amino acids are scrambled, indicating that the signal is sequence independent. Mutagenesis of different classes of amino acids within the signal identified charged residues (five basic and four acidic amino acids in 25 residues) as crucial determinants for sorting function, with amidated amino acids having a lesser role. Mutational analyses revealed that whereas charge balance (+1 overall) of the signal is unimportant, the total number of charged residues (nine), either positive or negative, is crucial for basolateral targeting. These data define a new class of targeting signal that relies on total charge and might provide a common mechanism for polarized trafficking of epithelial proteins. PMID- 20592188 TI - Oral antiplatelet therapy for the management of acute coronary syndromes: defining the role of prasugrel. AB - Antiplatelet therapy is important in the prevention of thrombosis, a significant cause of morbidity and mortality that is associated with acute coronary syndrome. Current evidence supports the general acceptance of aspirin and clopidogrel as the standard of care for the management of all patients experiencing an acute coronary syndrome with or without percutaneous coronary intervention. Thienopyridine antiplatelet agents such as clopidogrel, when used alone and in combination with aspirin, are effective in preventing myocardial infarction and death. Prasugrel, a potent antiplatelet agent that was recently approved by the Food and Drug Administration, may have some advantages over other antiplatelet agents, owing to its rapid onset of action, higher degree of platelet inhibition, and decreased interpatient variability in pharmacokinetics and pharmacodynamics as compared with clopidogrel. However, further studies are required to assess the potential for increased bleeding in high-risk patients. PMID- 20592189 TI - Traumatic brain injury: advanced multimodal neuromonitoring from theory to clinical practice. AB - Traumatic brain injury accounts for nearly 1.4 million injuries and 52 000 deaths annually in the United States. Intensive bedside neuromonitoring is critical in preventing secondary ischemic and hypoxic injury common to patients with traumatic brain injury in the days following trauma. Advancements in multimodal neuromonitoring have allowed the evaluation of changes in markers of brain metabolism (eg, glucose, lactate, pyruvate, and glycerol) and other physiological parameters such as intracranial pressure, cerebral perfusion pressure, cerebral blood flow, partial pressure of oxygen in brain tissue, blood pressure, and brain temperature. This article highlights the use of multimodal monitoring in the intensive care unit at a level I trauma center in the Pacific Northwest. The trends in and significance of metabolic, physiological, and hemodynamic factors in traumatic brain injury are reviewed, the technical aspects of the specific equipment used to monitor these parameters are described, and how multimodal monitoring may guide therapy is demonstrated. As a clinical practice, multimodal neuromonitoring shows great promise in improving bedside therapy in patients with traumatic brain injury, ultimately leading to improved neurological outcomes. PMID- 20592190 TI - The fusiform face area: in quest of holistic face processing. PMID- 20592191 TI - Predictive coding and the neural response to predictable stimuli. PMID- 20592192 TI - Autonomous CaMKII can promote either long-term potentiation or long-term depression, depending on the state of T305/T306 phosphorylation. AB - Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a key mediator of long-term potentiation (LTP). Whereas acute intracellular injection of catalytically active CaMKII fragments saturates LTP (Lledo et al., 1995), an autonomously active form (T286D) of CaMKII holoenzyme expressed in transgenic mice did not saturate potentiation (Mayford et al., 1995). To better understand the role of the holoenzyme in the control of synaptic strength, we transfected hippocampal neurons with constructs encoding forms of CaMKII mimicking different phosphorylation states. Surprisingly, T286D not only failed to potentiate synaptic strength, but produced synaptic depression through an long-term depression (LTD)-like process. T305/T306 phosphorylation was critical for this depression because overexpression of the pseudophosphorylated form (T286D/T305D/T306D) caused depression that occluded LTD, and overexpression of an autonomous form in which T305/T306 could not be phosphorylated (T286D/T305A/T306A) prevented LTD (instead producing potentiation). Therefore, autonomous CaMKII can lead to either LTP or LTD, depending on the phosphorylation state of the control point, T305/T306. PMID- 20592193 TI - 17-Beta-estradiol enhanced allodynia of inflammatory temporomandibular joint through upregulation of hippocampal TRPV1 in ovariectomized rats. AB - Temporomandibular disorders (TMDs) predominantly affect reproductive female patients, with pain the most frequent complaint. Although estrogens are believed to play important roles in TMD pain, the mechanism underlying modulation of TMD pain by estrogens remains largely unknown. Accumulating evidence implies that the hippocampus is involved in sexual dimorphism of pain sensitivity. In this study, we investigated the hippocampal TRPV1 (transient receptor potential vanilloid 1) expression in ovariectomized rats that received 17-beta-estradiol substitution and found that 17-beta-estradiol enhanced the mechanical allodynia of inflamed temporomandibular joint (TMJ) induced by complete Freund's adjuvant. Real-time PCR and immunoblotting demonstrated that TMJ inflammation significantly induced hippocampal TRPV1 expression compared with the control group but failed to induce it in the ovariectomized rats that received no estradiol replacement. In addition, estradiol potentiated TMJ inflammation-induced hippocampal TRPV1 expression in a dose-dependent manner in the ovariectomized rats. In contrast, TRPV1 transcription in amygdala, prefrontal cortex, and thalamus was not affected by TMJ inflammation and estradiol. Immunostaining showed TRPV1 localized in the processes and cytoplasm of pyramidal neurons in CA1-CA3 regions of the hippocampus. Moreover, intrahippocampal injection of TRPV1 antagonists capsazepine and 5'-iodo-resiniferatoxin into the CA1 region of the hippocampus significantly attenuated allodynia of inflamed TMJ in both nonovariectomized and ovariectomized rats that received estradiol replacement. Our results suggested that hippocampal TRPV1 can modulate central pain processing and estradiol may contribute to the sexual dimorphism of TMD pain sensitivity through upregulation of TRPV1 expression in the hippocampus. PMID- 20592194 TI - Hierarchical interaction structure of neural activities in cortical slice cultures. AB - Recent advances in the analysis of neuronal activities suggest that the instantaneous activity patterns can be mostly explained by considering only first order and pairwise interactions between recorded elements, i.e., action potentials or local field potentials (LFP), and do not require higher-than pairwise-order interactions. If generally applicable, this pairwise approach greatly simplifies the description of network interactions. However, an important question remains: are the recorded elements the units of interaction that best describe neuronal activity patterns? To explore this, we recorded spontaneous LFP peak activities in cortical organotypic cultures using planar, integrated 60 microelectrode arrays. We compared predictions obtained using a pairwise approach with those using a hierarchical approach that uses two different spatial units for describing the activity interactions: single electrodes and electrode clusters. In this hierarchical model, short-range interactions within each cluster were modeled by pairwise interactions of electrode activities and long range interactions were modeled by pairwise interactions of cluster activities. Despite the relatively low number of parameters used, the hierarchical model provided a more accurate description of the activity patterns than the pairwise model when applied to ensembles of 10 electrodes. Furthermore, the hierarchical model was successfully applied to a larger-scale data of approximately 60 electrodes. Electrode activities within clusters were highly correlated and spatially contiguous. In contrast, long-range interactions were diffuse, suggesting the presence of higher-than-pairwise-order interactions involved in the LFP peak activities. Thus, the identification of appropriate units of interaction may allow for the successful characterization of neuronal activities in large-scale networks. PMID- 20592196 TI - Visual function in mice with photoreceptor degeneration and transgenic expression of channelrhodopsin 2 in ganglion cells. AB - The progression of rod and cone degeneration in retinally degenerate (rd) mice ultimately results in a complete loss of photoreceptors and blindness. The inner retinal neurons survive and several recent studies using genetically targeted, light activated channels have made these neurons intrinsically light sensitive. We crossbred a transgenic mouse line expressing channelrhodopsin2 (ChR2) under the control of the Thy1 promoter with the Pde6b(rd1) mouse, a model for retinal degeneration (rd1/rd1). Approximately 30-40% of the ganglion cells of the offspring expressed ChR2. Extracellular recordings from ChR2-expressing ganglion cells in degenerated retinas revealed their intrinsic light sensitivity which was approximately 7 log U less sensitive than the scotopic threshold and approximately 2 log U less sensitive than photopic responses of normal mice. All ChR2-expressing ganglion cells were excited at light ON. The visual performance of rd1/rd1 mice and ChR2 rd1/rd1 mice was compared. Behavioral tests showed that both mouse strains had a pupil light reflex and they were able to discriminate light fields from dark fields in the visual water task. Cortical activity maps were recorded with optical imaging. The ChR2rd1/rd1 mice did not show a better visual performance than rd1/rd1 mice. In both strains the residual vision was correlated with the density of cones surviving in the peripheral retina. The expression of ChR2 under the control of the Thy1 promoter in retinal ganglion cells does not rescue vision. PMID- 20592195 TI - Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus. AB - Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs) and receive direct cholinergic innervation. We show here that functional alpha7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and alpha7-knock-out (alpha7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In alpha7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in alpha7KO mice. Interestingly, local infection with retroviral constructs to knockdown alpha7-mRNA mimics the alpha7KO phenotype, demonstrating that the relevant alpha7-nAChR signaling is cell autonomous. The results indicate a profound role for alpha7-nAChRs in adult neurogenesis and predict that alpha7 nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well. PMID- 20592197 TI - Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1. AB - Vertebrate photoreceptors have a modified cilium composed of a basal body, axoneme and outer segment. The outer segment includes stacked membrane discs, containing opsin and the signal transduction apparatus mediating phototransduction. In photoreceptors, two distinct classes of vesicles are trafficked. Synaptic vesicles are transported down the axon to the synapse, whereas opsin-containing vesicles are transported to the outer segment. The continuous replacement of the outer segments imposes a significant biosynthetic and trafficking burden on the photoreceptors. Here, we show that Ahi1, a gene that when mutated results in the neurodevelopmental disorder, Joubert syndrome (JBTS), is required for photoreceptor sensory cilia formation and the development of photoreceptor outer segments. In mice with a targeted deletion of Ahi1, photoreceptors undergo early degeneration. Whereas synaptic proteins are correctly trafficked, photoreceptor outer segment proteins fail to be transported appropriately or are significantly reduced in their expression levels (i.e., transducin and Rom1) in Ahi1(-/-) mice. We show that vesicular targeting defects in Ahi1(-/-) mice are cilium specific, and our evidence suggests that the defects are caused by a decrease in expression of the small GTPase Rab8a, a protein required for accurate polarized vesicular trafficking. Thus, our results suggest that Ahi1 plays a role in stabilizing the outer segment proteins, transducin and Rom1, and that Ahi1 is an important component of Rab8a-mediated vesicular trafficking in photoreceptors. The retinal degeneration observed in Ahi1(-/-) mice recapitulates aspects of the retinal phenotype observed in patients with JBTS and suggests the importance of Ahi1 in photoreceptor function. PMID- 20592198 TI - Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for Down syndrome. AB - Down syndrome (DS) is a genetic pathology characterized by intellectual disability and brain hypotrophy. Widespread neurogenesis impairment characterizes the fetal and neonatal DS brain, strongly suggesting that this defect may be a major determinant of mental retardation. Our goal was to establish, in a mouse model for DS, whether early pharmacotherapy improves neurogenesis and cognitive behavior. Neonate Ts65Dn mice were treated from postnatal day (P) 3 to P15 with fluoxetine, an antidepressant that inhibits serotonin (5-HT) reuptake and increases proliferation in the adult Ts65Dn mouse (Clark et al., 2006). On P15, they received a BrdU injection and were killed after either 2 h or 1 month. Results showed that P15 Ts65Dn mice had notably defective proliferation in the hippocampal dentate gyrus, subventricular zone, striatum, and neocortex and that proliferation was completely rescued by fluoxetine. In the hippocampus of untreated P15 Ts65Dn mice, we found normal 5-HT levels but a lower expression of 5-HT1A receptors and brain-derived neurotrophic factor (BDNF). In Ts65Dn mice, fluoxetine treatment restored the expression of 5-HT1A receptors and BDNF. One month after cessation of treatment, there were more surviving cells in the dentate gyrus of Ts65Dn mice, more cells with a neuronal phenotype, more proliferating precursors, and more granule cells. These animals were tested for contextual fear conditioning, a hippocampus-dependent memory task, and exhibited a complete recovery of memory performance. Results show that early pharmacotherapy with a drug usable by humans can correct neurogenesis and behavioral impairment in a model for DS. PMID- 20592199 TI - Selective attention modulates face-specific induced gamma oscillations recorded from ventral occipitotemporal cortex. AB - EEG studies from subdural electrodes have demonstrated a face-specific event related potential (face-N200) recorded from human ventral occipitotemporal cortex. The insensitivity of face-N200 to task manipulations has supported the proposal that face-N200 reflects an initial obligatory response to faces. This result stands in striking contrast to results of neuroimaging studies that have demonstrated strong task sensitivity of the fusiform hemodynamic response evoked by faces, and thus has created a paradox in the face perception literature. We recorded field potentials directly from the cortical surface of 16 patients while they selectively attended to faces or houses. Here we report that face-specific gamma activity recorded at face-N200 sites is strongly modulated by selective attention, while face-N200 is not. Our results reconcile prior electrophysiological and hemodynamic studies of face perception, and suggest that attentional modulation of the face response follows an initial phase that is largely insensitive to attention. PMID- 20592200 TI - Associative plasticity in the medial auditory thalamus and cerebellar interpositus nucleus during eyeblink conditioning. AB - Eyeblink conditioning, a type of associative motor learning, requires the cerebellum. The medial auditory thalamus is a necessary source of stimulus input to the cerebellum during auditory eyeblink conditioning. Nothing is currently known about interactions between the thalamus and cerebellum during associative learning. In the current study, neuronal activity was recorded in the cerebellar interpositus nucleus and medial auditory thalamus simultaneously from multiple tetrodes during auditory eyeblink conditioning to examine the relative timing of learning-related plasticity within these interconnected areas. Learning-related changes in neuronal activity correlated with the eyeblink conditioned response were evident in the cerebellum before the medial auditory thalamus over the course of training and within conditioning trials, suggesting that thalamic plasticity may be driven by cerebellar feedback. Short-latency plasticity developed in the thalamus during the first conditioning session and may reflect attention to the conditioned stimulus. Extinction training resulted in a decrease in learning-related activity in both structures and an increase in inhibition within the cerebellum. A feedback projection from the cerebellar nuclei to the medial auditory thalamus was identified, which may play a role in learning by facilitating stimulus input to the cerebellum via the thalamo-pontine projection. PMID- 20592201 TI - A novel postsynaptic mechanism for heterosynaptic sharing of short-term plasticity. AB - Postsynaptic release of Ca(2+) from intracellular stores is an important means of cellular signaling that mediates numerous forms of synaptic plasticity. Previous studies have identified a postsynaptic intracellular Ca(2+) requirement for a form of short-term plasticity, post-tetanic potentiation (PTP) at sensory neuron (SN)-motor neuron synapses in Aplysia. Here, we show that postsynaptic IP(3) mediated Ca(2+) release in response to a presynaptic tetanus in an SN that induces PTP can confer transient plasticity onto a neighboring SN synapse receiving subthreshold activation. This heterosynaptic sharing of plasticity represents a dynamic, short-term synaptic enhancement of synaptic inputs onto a common postsynaptic target. Heterosynaptic sharing is blocked by postsynaptic disruption of Ca(2+)- and IP(3)-mediated signaling, and, conversely, it is mimicked by postsynaptic injection of nonhydrolyzable IP(3), and by photolysis of caged IP(3) in the MN. The molecular mechanism for heterosynaptic sharing involves metabotropic glutamate receptors and Homer-dependent interactions, indicating that Homer can facilitate the integration of Ca(2+)-dependent plasticity at neighboring postsynaptic sites and provides a postsynaptic mechanism for the spread of plasticity induced by presynaptic activation. Our results support a model in which postsynaptic summation of IP(3) signals from suprathreshold and subthreshold inputs results in molecular coincidence detection that gives rise to a novel form of heterosynaptic plasticity. PMID- 20592202 TI - Activation of meningeal nociceptors by cortical spreading depression: implications for migraine with aura. AB - Attacks of migraine with aura represent a phenomenon in which abnormal neuronal activity in the cortex produces sensory disturbances (aura) some 20-40 min before the onset of headache. The purpose of this study was to determine whether cortical spreading depression (CSD)--an event believed to underlie visual aura- can give rise to activation of nociceptors that innervate the meninges--an event believed to set off migraine headache. CSD was induced in anesthetized male rats by stimulation of the visual cortex with electrical pulses, pin prick, or KCl; single-unit activity of meningeal nociceptors was monitored in vivo in the rat before and after CSD. Regardless of the method of cortical stimulation, induction of CSD was recorded in 64 trials. In 31 of those trials, CSD induced a twofold increase in meningeal nociceptor firing rate that persisted for 37.0 +/- 4.6 min in trials in which activity returned to baseline, or >68 min in trials in which activity remained heightened at the time recording was interrupted. In two-thirds of the trials, onset of long-lasting neuronal activation began approximately 14 min after the wave of CSD. The findings demonstrates for the first time that induction of CSD by focal stimulation of the rat visual cortex can lead to long lasting activation of nociceptors that innervate the meninges. We suggest that migraine with aura is initiated by waves of CSD that lead up to delayed activation of the trigeminovascular pathway. PMID- 20592203 TI - Cooperation and heterogeneity of the autistic mind. AB - Individuals with autism spectrum conditions (ASCs) have a core difficulty in recursively inferring the intentions of others. The precise cognitive dysfunctions that determine the heterogeneity at the heart of this spectrum, however, remains unclear. Furthermore, it remains possible that impairment in social interaction is not a fundamental deficit but a reflection of deficits in distinct cognitive processes. To better understand heterogeneity within ASCs, we employed a game-theoretic approach to characterize unobservable computational processes implicit in social interactions. Using a social hunting game with autistic adults, we found that a selective difficulty representing the level of strategic sophistication of others, namely inferring others' mindreading strategy, specifically predicts symptom severity. In contrast, a reduced ability in iterative planning was predicted by overall intellectual level. Our findings provide the first quantitative approach that can reveal the underlying computational dysfunctions that generate the autistic "spectrum." PMID- 20592204 TI - BACE1 deficiency causes altered neuronal activity and neurodegeneration. AB - BACE1 is required for the release of beta-amyloid (Abeta) in vivo, and inhibition of BACE1 activity is targeted for reducing Abeta generation in Alzheimer's patients. To further our understanding of the safe use of BACE1 inhibitors in human patients, we aimed to study the physiological functions of BACE1 by characterizing BACE1-null mice. Here, we report the finding of spontaneous behavioral seizures in BACE1-null mice. Electroencephalographic recordings revealed abnormal spike-wave discharges in BACE1-null mice, and kainic acid induced seizures also occurred more frequently in BACE1-null mice compared with their wild-type littermates. Biochemical and morphological studies showed that axonal and surface levels of Na(v)1.2 were significantly elevated in BACE1-null mice, consistent with the increased fast sodium channel current recorded from BACE1-null hippocampal neurons. Patch-clamp recording also showed altered intrinsic firing properties of isolated BACE1-null hippocampal neurons. Furthermore, population spikes were significantly increased in BACE1-null brain slices, indicating hyperexcitability of BACE1-null neurons. Together, our results suggest that increased sodium channel activity contributes to the epileptic behaviors observed in BACE1-null mice. The knowledge from this study is crucial for the development of BACE1 inhibitors for Alzheimer's therapy and to the applicative study of epilepsy. PMID- 20592205 TI - Protein Phosphatase 2a and glycogen synthase kinase 3 signaling modulate prepulse inhibition of the acoustic startle response by altering cortical M-Type potassium channel activity. AB - There is considerable interest in the regulation of sensorimotor gating, since deficits in this process could play a critical role in the symptoms of schizophrenia and other psychiatric disorders. Sensorimotor gating is often studied in humans and rodents using the prepulse inhibition of the acoustic startle response (PPI) model, in which an acoustic prepulse suppresses behavioral output to a startle-inducing stimulus. However, the molecular and neural mechanisms underlying PPI are poorly understood. Here, we show that a regulatory pathway involving protein phosphatase 2A (PP2A), glycogen synthase kinase 3 beta (GSK3beta), and their downstream target, the M-type potassium channel, regulates PPI. Mice (Mus musculus) carrying a hypomorphic allele of Ppp2r5delta, encoding a regulatory subunit of PP2A, show attenuated PPI. This PPP2R5delta reduction increases the phosphorylation of GSK3beta at serine 9, which inactivates GSK3beta, indicating that PPP2R5delta positively regulates GSK3beta activity in the brain. Consistently, genetic and pharmacological manipulations that reduce GSK3beta function attenuate PPI. The M-type potassium channel subunit, KCNQ2, is a putative GSK3beta substrate. Genetic reduction of Kcnq2 also reduces PPI, as does systemic inhibition of M-channels with linopirdine. Importantly, both the GSK3 inhibitor 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)1H-pyrrole-2,5 dione (SB216763) and linopirdine reduce PPI when directly infused into the medial prefrontal cortex (mPFC). Whole-cell electrophysiological recordings of mPFC neurons show that SB216763 and linopirdine have similar effects on firing, and GSK3 inhibition occludes the effects of M-channel inhibition. These data support a previously uncharacterized mechanism by which PP2A/GSK3beta signaling regulates M-type potassium channel activity in the mPFC to modulate sensorimotor gating. PMID- 20592207 TI - LKB1-mediated spatial control of GSK3beta and adenomatous polyposis coli contributes to centrosomal forward movement and neuronal migration in the developing neocortex. AB - Neuronal migration is an essential process for the development of the cerebral cortex. We have previously shown that LKB1, an evolutionally conserved polarity kinase, plays a critical role in neuronal migration in the developing neocortex. Here we show that LKB1 mediates Ser9 phosphorylation of GSK3beta to inactivate the kinase at the leading process tip of migrating neurons in the developing neocortex. This enables the microtubule plus-end binding protein adenomatous polyposis coli (APC) to localize at the distal ends of microtubules in the tip, thereby stabilizing microtubules near the leading edge. We also show that LKB1 activity, Ser9 phosphorylation of GSK3beta, and APC binding to the distal ends of microtubules are required for the microtubule stabilization in the leading process tip, centrosomal forward movement, and neuronal migration. These findings suggest that LKB1-induced spatial control of GSK3beta and APC at the leading process tip mediates the stabilization of microtubules within the tip and is critical for centrosomal forward movement and neuronal migration in the developing neocortex. PMID- 20592206 TI - Lateral mobility of nicotinic acetylcholine receptors on neurons is determined by receptor composition, local domain, and cell type. AB - The lateral mobility of surface receptors can define the signaling properties of a synapse and rapidly change synaptic function. Here we use single-particle tracking with Quantum Dots to follow nicotinic acetylcholine receptors (nAChRs) on the surface of chick ciliary ganglion neurons in culture. We find that both heteropentameric alpha3-containing receptors (alpha3*-nAChRs) and homopentameric alpha7-containing receptors (alpha7-nAChRs) access synaptic domains by lateral diffusion. They have comparable mobilities and display Brownian motion in extrasynaptic space but are constrained and move more slowly in synaptic space. The two receptor types differ in the nature of their synaptic restraints. Disruption of lipid rafts, PDZ-containing scaffolds, and actin filaments each increase the mobility of alpha7-nAChRs in synaptic space while collapse of microtubules has no effect. The opposite is seen for alpha3*-nAChRs where synaptic mobility is increased only by microtubule collapse and not the other manipulations. Other differences are found for regulation of alpha3*-nAChR and alpha7-nAChR mobilities in extrasynaptic space. Most striking are effects on the immobile populations of alpha7-nAChRs and alpha3*-nAChRs. Disruption of either lipid rafts or PDZ scaffolds renders half of the immobile alpha3*-nAChRs mobile without changing the proportion of immobile alpha7-nAChRs. Similar results were obtained with chick sympathetic ganglion neurons, though regulation of receptor mobility differed in at least one respect from that seen with ciliary ganglion neurons. Control of nAChR lateral mobility, therefore, is determined by mechanisms that are domain specific, receptor subtype dependent, and cell-type constrained. The outcome is a system that could tailor nicotinic signaling capabilities to specific needs of individual locations. PMID- 20592208 TI - The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus. AB - The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects episodic memory and affective behaviors. However, the precise role of the BDNF Val66Met polymorphism in hippocampal synaptic transmission and plasticity has not yet been studied. Therefore, we examined synaptic properties in the hippocampal CA3-CA1 synapses of BDNF(Met/Met) mice and matched wild-type mice. Although basal glutamatergic neurotransmission was normal, both young and adult mice showed a significant reduction in NMDA receptor-dependent long-term potentiation. We also found that NMDA receptor-dependent long-term depression was decreased in BDNF(Met/Met) mice. However, mGluR-dependent long-term depression was not affected by the BDNF Val66Met polymorphism. Consistent with the NMDA receptor-dependent synaptic plasticity impairment, we observed a significant decrease in NMDA receptor neurotransmission in the CA1 pyramidal neurons of BDNF(Met/Met) mice. Thus, these results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus. PMID- 20592209 TI - Synaptic scaling and the development of a motor network. AB - Neurons respond homeostatically to chronic changes in network activity with compensatory changes such as a uniform alteration in the size of miniature postsynaptic current (mPSC) amplitudes termed synaptic scaling. However, little is known about the impact of synaptic scaling on the function of neural networks in vivo. We used the embryonic zebrafish to address the effect of synaptic scaling on the neural network underlying locomotion. Activity was decreased during development by TTX injection to block action potentials or CNQX injection to block glutamatergic transmission. Alternatively TNFalpha was chronically applied. Recordings from spinal neurons showed that glutamatergic mPSCs scaled up approximately 25% after activity reduction and fortuitously scaled down approximately 20% after TNFalpha treatment, and were unchanged following blockade of neuromuscular activity alone with alpha-bungarotoxin. Regardless of the direction of scaling, immediately following reversal of treatment no chronic effect was distinguishable in motoneuron activity patterns or in swimming behavior. We also acutely induced a similar increase of glutamatergic mPSC amplitudes using cyclothiazide to reduce AMPA receptor desensitization or decrease of glutamatergic mPSC amplitudes using a low concentration of CNQX to partially block AMPA receptors. Though the strength of the motor output was altered, neither chronic nor acute treatments disrupted the patterning of synaptic activity or swimming. Our results show, for the first time, that scaling of glutamatergic synapses can be induced in vivo in the zebrafish and that synaptic patterning is less plastic than synaptic strength during development. PMID- 20592210 TI - Rapid formation of spatiotopic representations as revealed by inhibition of return. AB - Inhibition of return (IOR), a performance decrement for stimuli appearing at recently cued locations, occurs when the target and cue share the same screen position. This is in contrast to cue-based attention facilitation effects that were recently suggested to be mapped in a retinotopic reference frame, the prevailing representation throughout early visual processing stages. Here, we investigate the dynamics of IOR in both reference frames, using a modified cued location saccadic reaction time task with an intervening saccade between cue and target presentation. Thus, on different trials, the target was present either at the same retinotopic location as the cue, or at the same screen position (e.g., spatiotopic location). IOR was primarily found for targets appearing at the same spatiotopic position as the initial cue, when the cue and target were presented at the same hemifield. This suggests that there is restricted information transfer of cue position across the two hemispheres. Moreover, the effect was maximal when the target was presented 10 ms after the intervening saccade ended and was attenuated in longer delays. In our case, therefore, the representation of previously attended locations (as revealed by IOR) is not remapped slowly after the execution of a saccade. Rather, either a retinotopic representation is remapped rapidly, adjacent to the end of the saccade (using a prospective motor command), or the positions of the cue and target are encoded in a spatiotopic reference frame, regardless of eye position. Spatial attention can therefore be allocated to target positions defined in extraretinal coordinates. PMID- 20592211 TI - Dopamine, time, and impulsivity in humans. AB - Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system. PMID- 20592212 TI - Functional organization of human motor cortex: directional selectivity for movement. AB - In monkeys, neurons in the hand representation of the primary motor cortex (M1) are often tuned to the direction of hand movement, and there is evidence that these neurons are clustered according to their "preferred" direction of movement. However, this organizational principle has yet to be demonstrated in M1 of humans. We conducted a functional magnetic resonance imaging (fMRI) study in which participants used a joystick to move a cursor from a central origin to one of five equidistant targets. The fMRI signal of individual voxels was sensitive to the directional aspects of the reaching task and manifested direction-specific adaptation. Furthermore, the correlation between multivoxel patterns of responses for different movement directions depended on the angular distance between them. We conclude that M1 neurons are likely to be organized in clusters according to their preferred direction, since only such a coarse-grained representation can lead to directional selectivity of voxels, encompassing millions of neurons. A simple model that estimates cluster size suggests that the diameter of these clusters is on the order of a few hundred micrometers. PMID- 20592214 TI - Electrophysiological localization of eyeblink-related microzones in rabbit cerebellar cortex. AB - The classically conditioned eyeblink response in the rabbit is one of the best characterized behavioral models of associative learning. It is cerebellum dependent, with many studies indicating that the hemispheral part of Larsell's cerebellar cortical lobule VI (HVI) is critical for the acquisition and performance of learned responses. However, there remain uncertainties about the distribution of the critical regions within and around HVI. In this learning, the unconditional stimulus is thought to be carried by periocular-activated climbing fibers. Here, we have used a microelectrode array to perform systematic, high resolution, electrophysiological mapping of lobule HVI and surrounding folia in rabbits, to identify regions with periocular-evoked climbing fiber activity. Climbing fiber local field potentials and single-unit action potentials were recorded, and electrode locations were reconstructed from histological examination of brain sections. Much of the sampled cerebellar cortex, including large parts of lobule HVI, was unresponsive to periocular input. However, short latency ipsilateral periocular-evoked climbing fiber responses were reliably found within a region in the ventral part of the medial wall of lobule HVI, extending to the base of the primary fissure. Small infusions of the AMPA/kainate receptor antagonist CNQX into this electrophysiologically defined region in awake rabbits diminished or abolished conditioned responses. The known parasagittal zonation of the cerebellum, supported by zebrin immunohistochemistry, indicates that these areas have connections consistent with an essential role in eyeblink conditioning. These small eyeblink-related areas provide cerebellar cortical targets for analysis of eyeblink conditioning at a neuronal level but need to be localized with electrophysiological identification in individual animals. PMID- 20592213 TI - Repetition priming of motoneuronal activity in a small motor network: intercellular and intracellular signaling. AB - The characteristics of central pattern generator (CPG) outputs are subject to extensive modulation. Previous studies of neuromodulation largely focused on immediate actions of neuromodulators, i.e., actions that were exerted at the time when either neuromodulators were present or neuromodulatory inputs to the CPG were active. However, neuromodulatory actions are known to persist when neuromodulators are no longer present. In Aplysia, stimulation of cerebral-buccal interneuron-2 (CBI-2), which activates the feeding CPG, produces a repetition priming of motor programs. This priming is reflected in an increase of firing of motoneurons. As CBI-2 contains two neuromodulatory peptides, FCAP (feeding circuit-activating peptide) and CP2 (cerebral peptide 2), we hypothesized that repetition priming may involve persistent peptidergic neuromodulation. We find that these peptides produce priming-like effects, i.e., they increase the firing of radula-opening (B48) and radula-closing (B8) motoneurons during motor programs. Proekt et al. (2004, 2007) showed that repetition priming of neuron B8 is implemented by modulatory inputs that B8 receives from the CPG. In contrast, our current findings indicate that priming of B48 may be implemented by a direct peptidergic modulation of its intrinsic characteristics via a pathway that activates cAMP. We suggest that the direct versus indirect, i.e., CPG-dependent, repetition priming may be related to the type of input that individual motoneurons receive from the CPG. We suggest that in motoneurons that are driven by concurrent excitation-inhibition, repetition priming is indirect as it is preferentially implemented via modulation of the output of CPGs. In contrast, in motoneurons that are driven by alternating excitation-inhibition, direct modulation of motoneurons may be preferentially used. PMID- 20592215 TI - Temporal and spatial characteristics of vibrissa responses to motor commands. AB - A mechanistic description of the generation of whisker movements is essential for understanding the control of whisking and vibrissal active touch. We explore how facial-motoneuron spikes are translated, via an intrinsic muscle, to whisker movements. This is achieved by constructing, simulating, and analyzing a computational, biomechanical model of the motor plant, and by measuring spiking to movement transformations at small and large angles using high-precision whisker tracking in vivo. Our measurements revealed a supralinear summation of whisker protraction angles in response to consecutive motoneuron spikes with moderate interspike intervals (5 ms < Deltat < 30 ms). This behavior is explained by a nonlinear transformation from intracellular changes in Ca(2+) concentration to muscle force. Our model predicts the following spatial constraints: (1) Contraction of a single intrinsic muscle results in movement of its two attached whiskers with different amplitudes; the relative amplitudes depend on the resting angles and on the attachment location of the intrinsic muscle on the anterior whisker. Counterintuitively, for a certain range of resting angles, activation of a single intrinsic muscle can lead to a retraction of one of its two attached whiskers. (2) When a whisker is pulled by its two adjacent muscles with similar forces, the protraction amplitude depends only weakly on the resting angle. (3) Contractions of two adjacent muscles sums up linearly for small amplitudes and supralinearly for larger amplitudes. The model provides a direct translation from motoneuron spikes to whisker movements and can serve as a building block in closed-loop motor-sensory models of active touch. PMID- 20592216 TI - Elevated phosphatidylinositol 3,4,5-trisphosphate in glia triggers cell autonomous membrane wrapping and myelination. AB - In the developing nervous system, constitutive activation of the AKT/mTOR (mammalian target of rapamycin) pathway in myelinating glial cells is associated with hypermyelination of the brain, but is reportedly insufficient to drive myelination by Schwann cells. We have hypothesized that it requires additional mechanisms downstream of NRG1/ErbB signaling to trigger myelination in the peripheral nervous system. Here, we demonstrate that elevated levels of phosphatidylinositol 3,4,5-trisphosphate (PIP3) have developmental effects on both oligodendrocytes and Schwann cells. By generating conditional mouse mutants, we found that Pten-deficient Schwann cells are enhanced in number and can sort and myelinate axons with calibers well below 1 microm. Unexpectedly, mutant glial cells also spirally enwrap C-fiber axons within Remak bundles and even collagen fibrils, which lack any membrane surface. Importantly, PIP3-dependent hypermyelination of central axons, which is observed when targeting Pten in oligodendrocytes, can also be induced after tamoxifen-mediated Cre recombination in adult mice. We conclude that it requires distinct PIP3 effector mechanisms to trigger axonal wrapping. That myelin synthesis is not restricted to early development but can occur later in life is relevant to developmental disorders and myelin disease. PMID- 20592217 TI - The endocannabinoid 2-arachidonoyl-glycerol controls odor sensitivity in larvae of Xenopus laevis. AB - Cannabinoids modulate the activity of many neuronal cells, among them sensory neurons in the olfactory epithelium. Here we show that the endocannabinoid 2 arachidonoyl-glycerol (2-AG) is synthesized in both olfactory receptor neurons and glia-like sustentacular cells in larval Xenopus laevis. Its production in the latter depends on the hunger state of the animal. The essential effect of 2-AG in olfactory receptor neurons is the control of odorant detection thresholds via cannabinoid CB(1) receptor activation. Hunger renders olfactory neurons more sensitive. Endocannabinoid modulation in the nose may therefore substantially influence food-seeking behavior. PMID- 20592218 TI - Bepridil and amiodarone simultaneously target the Alzheimer's disease beta- and gamma-secretase via distinct mechanisms. AB - The two proteases beta-secretase and gamma-secretase generate the amyloid beta peptide and are drug targets for Alzheimer's disease. Here we tested the possibility of targeting the cellular environment of beta-secretase cleavage instead of the beta-secretase enzyme itself. beta-Secretase has an acidic pH optimum and cleaves the amyloid precursor protein in the acidic endosomes. We identified two drugs, bepridil and amiodarone, that are weak bases and are in clinical use as calcium antagonists. Independently of their calcium-blocking activity, both compounds mildly raised the membrane-proximal, endosomal pH and inhibited beta-secretase cleavage at therapeutically achievable concentrations in cultured cells, in primary neurons, and in vivo in guinea pigs. This shows that an alkalinization of the cellular environment could be a novel therapeutic strategy to inhibit beta-secretase. Surprisingly, bepridil and amiodarone also modulated gamma-secretase cleavage independently of endosomal alkalinization. Thus, both compounds act as dual modulators that simultaneously target beta- and gamma-secretase through distinct molecular mechanisms. In addition to Alzheimer's disease, compounds with dual properties may also be useful for drug development targeting other membrane proteins. PMID- 20592219 TI - Evidence that myosin activity opposes microtubule-based axonal transport of mitochondria. AB - Neurons transport and position mitochondria using a combination of saltatory, bidirectional movements and stationary docking. Axonal mitochondria move along microtubules (MTs) using kinesin and dynein motors, but actin and myosin also play a poorly defined role in their traffic. To ascertain this role, we have used RNA interference (RNAi) to deplete specific myosin motors in cultured Drosophila neurons and quantified the effects on mitochondrial motility. We produced a fly strain expressing the Caenorhabditis elegans RNA transporter SID-1 in neurons to increase the efficacy of RNAi in primary cultures. These neurons exhibited significantly increased RNAi-mediated knockdown of gene expression compared with neurons not expressing this transporter. Using this system, we observed a significant increase in mitochondrial transport during myosin V depletion. Mitochondrial mean velocity and duty cycle were augmented in both anterograde and retrograde directions, and the fraction of mitochondrial flux contained in long runs almost doubled for anterograde movement. Myosin VI depletion increased the same movement parameters but was selective for retrograde movement, whereas myosin II depletion produced no phenotype. An additional effect of myosin V depletion was an increase in mitochondrial length. These data indicate that myosin V and VI play related but distinct roles in regulating MT-based mitochondrial movement: they oppose, rather than complement, protracted MT-based movements and perhaps facilitate organelle docking. PMID- 20592220 TI - Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy. AB - Perisomatic inhibition from basket cells plays an important role in regulating pyramidal cell output. Two major subclasses of CA1 basket cells can be identified based on their expression of either cholecystokinin (CCK) or parvalbumin. This study examined their fates in the mouse pilocarpine model of temporal lobe epilepsy. Overall, immunohistochemical labeling of GABAergic boutons in the pyramidal cell layer of CA1 was preserved in the mouse model. However, CCK labeled boutons in this layer were chronically reduced, whereas parvalbumin containing boutons were conserved. Immunohistochemistry for cannabinoid receptor 1 (CB(1)), another marker for CCK-containing basket cells, also labeled fewer boutons in pilocarpine-treated mice. Hours after status epilepticus, electron microscopy revealed dark degenerating terminals in the pyramidal cell layer with lingering CCK and CB(1) immunoreactivity. In mice with recurrent seizures, carbachol-induced enhancement of spontaneous IPSCs (sIPSCs) originating from CCK containing basket cells was accordingly reduced in CA1 pyramidal cells. By suppressing sIPSCs from CCK-expressing basket cells, a CB(1) agonist reverted the stimulatory effects of carbachol in naive mice to levels comparable with those observed in cells from epileptic mice. The agatoxin-sensitive component of CA1 pyramidal cell sIPSCs from parvalbumin-containing interneurons was increased in pilocarpine-treated mice, and miniature IPSCs were reduced, paralleling the decrease in CCK-labeled terminals. Altogether, the findings are consistent with selective reduction in perisomatic CA1 pyramidal cell innervation from CCK expressing basket cells in mice with spontaneous seizures and a greater reliance on persisting parvalbumin innervation. This differential alteration in inhibition may contribute to the vulnerability of the network to seizure activity. PMID- 20592222 TI - Postural stability changes during the prism adaptation test in patients with intermittent and constant exotropia. AB - PURPOSE: Computerized static stabilometry is a clinical test in neurologic and muscular diseases to assess postural stability or body sway in a quantitative manner. The purpose of this study was to examine whether postural stability would change in the process of the prism adaptation test in patients with intermittent and constant exotropia. METHODS: Postural stability was measured before the prism adaptation test and immediately, 15 minutes, and 60 minutes after the prism adaptation test by computerized static stabilometry in 17 consecutive adult patients with exotropia, including 10 patients with intermittent exotropia and seven with constant exotropia. Stabilometric parameters were compared between patients with intermittent and those with constant exotropia for 60 minutes by repeated-measures analysis of variance as statistical analysis. RESULTS: The Romberg quotients for the root mean square areas of the sway path (cm(2)), the area in the condition of the patients' eyes open, divided by that in the condition of the patients' eyes closed, increased significantly in the time course of the prism adaptation test and returned to the pretest level in patients with intermittent exotropia and in patients with constant exotropia (P = 0.0173). No significant difference in the Romberg quotients was noted between the patients with intermittent exotropia and those with constant exotropia. CONCLUSIONS: Postural instability became more pronounced by the prism adaptation test in the patients with exotropia. Binocular visual and motor perceptional changes induced by the prism adaptation test could lead to postural instability, with adaptation taking place 60 minutes after the start of the test. PMID- 20592221 TI - Sleep and brain energy levels: ATP changes during sleep. AB - Sleep is one of the most pervasive biological phenomena, but one whose function remains elusive. Although many theories of function, indirect evidence, and even common sense suggest sleep is needed for an increase in brain energy, brain energy levels have not been directly measured with modern technology. We here report that ATP levels, the energy currency of brain cells, show a surge in the initial hours of spontaneous sleep in wake-active but not in sleep-active brain regions of rat. The surge is dependent on sleep but not time of day, since preventing sleep by gentle handling of rats for 3 or 6 h also prevents the surge in ATP. A significant positive correlation was observed between the surge in ATP and EEG non-rapid eye movement delta activity (0.5-4.5 Hz) during spontaneous sleep. Inducing sleep and delta activity by adenosine infusion into basal forebrain during the normally active dark period also increases ATP. Together, these observations suggest that the surge in ATP occurs when the neuronal activity is reduced, as occurs during sleep. The levels of phosphorylated AMP activated protein kinase (P-AMPK), well known for its role in cellular energy sensing and regulation, and ATP show reciprocal changes. P-AMPK levels are lower during the sleep-induced ATP surge than during wake or sleep deprivation. Together, these results suggest that sleep-induced surge in ATP and the decrease in P-AMPK levels set the stage for increased anabolic processes during sleep and provide insight into the molecular events leading to the restorative biosynthetic processes occurring during sleep. PMID- 20592223 TI - Complement factor h autoantibodies and age-related macular degeneration. AB - PURPOSE: In this case-control study, the hypothesis that factor H autoantibodies are associated with age-related macular degeneration (AMD) was examined. METHODS: One hundred AMD patients (median age, 78 years), 98 age-matched control subjects (median age, 78 years) known not to have AMD, and 100 healthy blood donors (median age, 43 years) were enrolled. An enzyme-linked immunosorbent assay (ELISA) was used to screen for complement factor H autoantibodies and either quantitative polymerase chain reaction (qPCR) or multiplex ligation-dependent probe amplification (MLPA) were performed to measure the copy number of the gene encoding complement factor H-related protein 3 (CFHR3). RESULTS: There was a significant difference in the median complement factor H autoantibody titer between the three groups (AMD patients, 196 reference units [RU]]; age-match control subjects, 316 RU; and blood donor control subjects, 121 RU; Kruskal Wallis test, P < 0.001). Pair-wise comparison (Mann-Whitney test) showed that all three groups were significantly different from each other. Two different thresholds were used in the healthy blood donors to identify individuals with complement factor H autoantibodies. Both suggested that the prevalence of factor H autoantibodies was decreased in AMD patients. The CFHR3 copy number was measured as a surrogate for the deletion of the genes encoding complement factor H-related proteins 3 and 1 (CFHR3/1). The allele frequency of the deletion was significantly higher in the age-matched control subjects than in the AMD patients (22.2% vs. 8.2%). CONCLUSIONS: The level of factor H autoantibodies is lower in AMD patients than in age-matched control subjects. PMID- 20592224 TI - Multiplex cytokine analysis reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. AB - PURPOSE: To test the hypothesis that immune activation occurs in glaucoma by comparing concentrations of multiple cytokines in aqueous humor (AH) from patients with primary open angle glaucoma (POAG) and from cataract patients without glaucoma as controls. METHODS: Cytokine concentrations in AH obtained during surgery were measured using microparticle-based immunoassays. Localized expression of IL-8 protein was investigated by immunohistochemistry of human eyes. RESULTS: Eight cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-10, IL-12, IFN gamma, and TNF-alpha) were below the limits of detection, and two cytokines (IL 18 and IL-15) were detected at low levels or in only a few patients. Although IL 6 was detected in 26 of 30 control patients (median, 2.7 pg/mL) and in 23 of 29 POAG patients (median, 1.6 pg/mL), the difference was not statistically significant. IL-8 was detected in 28 of 30 control patients (median, 1.8 pg/mL) and in all 29 POAG patients (median, 4.9 pg/mL). The higher IL-8 concentration in the AH of POAG patients was statistically significant (P < 0.001). In pairs of eyes from patients with asymmetric glaucomatous optic nerve damage, IL-8 concentration was higher in the AH of the more severely affected eye (P < 0.05). Patients with severe visual field defects had higher IL-8 concentrations in the AH than did patients with mild visual field defects. IL-8 protein expression was found in human retina and optic nerve. CONCLUSIONS: Concentration of the inflammatory cytokine IL-8 is significantly elevated in the AH of POAG patients, supporting the hypothesis that immune activation occurs in glaucoma. PMID- 20592225 TI - VIP promotes resistance in the Pseudomonas aeruginosa-infected cornea by modulating adhesion molecule expression. AB - PURPOSE: This study tested the hypothesis that the neuropeptide vasoactive intestinal peptide (VIP) regulates adhesion molecule expression, reduces inflammatory cell migration and infiltration into the Pseudomonas aeruginosa infected cornea of susceptible B6 mice, and promotes corneal healing and resistance. METHODS: B6 mice received daily intraperitoneal (IP) injections of VIP from -1 through 5 days after infection. Control mice were similarly injected with sterile phosphate-buffered saline (PBS). Transcript levels of adhesion molecules were determined by PCR array, then select molecules were tested individually by real-time reverse transcriptase-polymerase chain reaction (RT PCR) and confirmed at the protein level by enzyme-linked immunosorbent assay (ELISA) or immunofluorescent staining with confocal laser scanning microscopy at various time points after infection to assess the effects of VIP treatment in the regulation of adhesion molecule expression. RESULTS: Injection of B6 mice with VIP compared with PBS resulted in significant downregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, platelet endothelial cell adhesion molecule-1, and P-selectin and L-selectin mRNA expression. Protein levels for ICAM-1 and VCAM-1, detected by ELISA, supported the mRNA data at similar time points. Immunofluorescence staining further confirmed the effects of VIP treatment, showing reduced corneal expression of ICAM-1/leukocyte function-associated antigen (LFA-1) and VCAM-1/very late antigen 4 (VLA-4) at select time points compared with PBS-treated animals. CONCLUSIONS: VIP treatment downregulates the production of adhesion molecules integral to the transmigration process of host inflammatory cells (polymorphonuclear neutrophils, macrophages) into the infected cornea. This results directly in reduced cellular infiltration, less stromal destruction, and better disease outcome. PMID- 20592227 TI - Alpha2-adrenergic receptors and their core involvement in the process of axonal growth in retinal explants. AB - PURPOSE: To determine the patterns of alpha2-adrenergic receptor (alpha2-AR) subtype expression in normal and degenerated retinas and to analyze the response of these receptors to the alpha2-AR agonist brimonidine tartrate (BT). METHODS: The binding characteristics of alpha2-ARs in the retina were evaluated in experimental and matching sham groups by in vitro quantitative autoradiographic saturation with [(3)H]-clonidine. Retinal explants from juvenile and adult rats with either elevated intraocular pressure or after optic nerve crush (ONC) were cultured with BT over 96 hours in vitro to analyze the effects of BT on axonal growth by videomicroscopy and axon counting. Changes in retinal protein expression by BT were monitored by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). RESULTS: The total number of alpha2-ARs in the retina increased significantly after ONC compared with the sham group. BT supported axonal growth in the juvenile, glaucomatous, and injured retinas (P < 0.004) most effectively at a concentration of 0.001 mg/mL, without influencing the axonal growth rate. Immediate supplementation of BT was more effective than delayed supplementation (P < 0.001). Proteomic analysis revealed treatment-specific expression patterns of glial fibrillary acidic protein (GFAP), glucose-related protein (GRP)58, platelet-activating factor (PAF), and laminin-binding protein (LBP). CONCLUSIONS: These data are the first to show differences in alpha2-AR expression in normal and degenerated retinas. BT supports neuronal growth in cultured retinal pieces, suggesting that alpha2-ARs play a role in retinal metabolism. PMID- 20592226 TI - Ubiquitin proteasome pathway-mediated degradation of proteins: effects due to site-specific substrate deamidation. AB - PURPOSE: The accumulation, aggregation, and precipitation of proteins is etiologic for age-related diseases, particularly cataract, because the precipitates cloud the lens. Deamidation of crystallins is associated with protein precipitation, aging, and cataract. Among the roles of the ubiquitin proteasome pathway (UPP) is protein surveillance and maintenance of protein quality. The purpose of this study was to determine whether deamidation can alter clearance of crystallins by the UPP. METHODS: Wild-type (WT) and deamidated crystallins were expressed and (125)I-radiolabeled. Ubiquitination and degradation were monitored separately. RESULTS: For betaB2 crystallins, rates of ubiquitination and adenosine triphosphate-dependent degradation, both indicators of active UPP, occurred in the order Q70E/Q162E>Q162E> Q70E=WT betaB2 using reticulocyte lysate as the source of degradation machinery. Human lens epithelial cell lysates and lens fiber cell lysates also catalyzed ubiquitination but only limited degradation. Supplementation with proteasome failed to enhance degradation. Rates of ubiquitination and degradation of WT and deamidated betaB1 crystallins were rapid and showed little relationship to the site of deamidation using N157D and Q204E mutants. gammaD-Crystallins were not degraded by the UPP. Deamidation altered amine reactivity, circular dichroism spectra, surface hydrophobicity, and thermal stability. CONCLUSIONS: These data demonstrate for the first time that, like mild oxidative stress, deamidation of some proteins makes them preferred substrates for ubiquitination and, in some cells, for UPP dependent degradation. Failure to properly execute ubiquitination and degrade the ubiquitin-conjugates may explain their accumulation on aging and in cataractogenesis. PMID- 20592228 TI - Defective myogenic response to posture change in retinal vessels of well controlled type 1 diabetic patients with no retinopathy. AB - PURPOSE: The current approach to the prevention of diabetic retinopathy relies on intensive anti-diabetes treatment and is only partially successful. A marker of retinopathy risk would enable strategies of surveillance, screening of adjunct drugs, and targeted drug interventions. The authors sought to identify early abnormalities of retinal vessels that are not prevented by the current therapeutic approach. METHODS: Retinal thickness (an informer of vascular permeability) and hemodynamic parameters at baseline and longitudinally were measured in 27 subjects (age, 32 +/- 9 years [mean +/- SD]) with well-controlled type 1 diabetes of 12.4 +/- 6.4 years' duration and no retinopathy, and in 27 control subjects. In a subset of 17 patients and 11 controls, the hemodynamic response to reclining, a postural change that increases retinal perfusion pressure, was measured. RESULTS: Baseline foveal thickness and hemodynamic parameters were similar in the diabetic and control subjects. Foveal thickness increased over 12 months in the diabetic subjects, from 217 +/- 22 MUm to 222 +/- 20 MUm (P = 0.0036), remaining however within the normal range. Reclining uncovered in 47% of diabetic subjects (P = 0.016 compared with controls) an absent myogenic response (i.e., unchanged or increased arterial diameter instead of the normal decrease). The patterns were repeatable. Only the diabetic group with defective vasoconstriction showed widening arterial diameter over 12 months, a change presaging vascular dilatation in diabetic retinopathy. CONCLUSIONS: Defective myogenic response to pressure was the first detectable abnormality of retinal vessels in subjects with well-controlled type 1 diabetes. Because of its selective occurrence, interpretability in individual patients, and pathogenic potential, the abnormality deserves evaluation as a risk marker for retinopathy. PMID- 20592229 TI - Sphingosine-1-phosphate enhancement of cortical actomyosin organization in cultured human Schlemm's canal endothelial cell monolayers. AB - PURPOSE: Perfusion of sphingosine-1-phosphate (S1P) in whole eye organ culture models decreases outflow facility, whereas S1P promotes stress fiber formation and contractility in cultured trabecular meshwork (TM) cells. Because of S1P's known effect of increasing barrier function in endothelial cells, the authors hypothesized that Schlemm's canal (SC) cells in culture respond to S1P by increasing actomyosin organization at the cell cortex. METHODS: Using primary cultures of human SC cells, the authors determined S1P activation of the GTP binding proteins, RhoA and Rac (1,2,3). Time- and dose-dependent myosin light chain (MLC) phosphorylation in response to S1P and total expression of MLC were determined. Immunocytochemistry after S1P treatment was used to monitor filamentous actin (F-actin) and phospho-MLC organization and the localization of beta-catenin, a component of adherens junctions. TM and human umbilical vein endothelial cell monolayers were used as controls. RESULTS: S1P (1 MUM) activated RhoA and Rac after 5- and 30-minute treatments. S1P increased MLC phosphorylation with a similar time- and dose-dependent response in SC (EC(50) = 0.83 MUM) compared with TM (EC(50) = 1.33 MUM), though MLC expression was significantly greater in TM. In response to 1 MUM S1P treatment, phospho-MLC concentrated in the SC cell periphery, coincident with cortical actin assembly and recruitment of beta-catenin to the cell periphery. CONCLUSIONS: Results obtained in this study support the hypothesis that S1P increases actomyosin organization at the SC cell cortex and promotes intercellular junctions at the level of the inner wall of SC to increase transendothelial resistance and in part explains the S1P-induced decrease of outflow facility in organ culture. PMID- 20592230 TI - Effects of silicone hydrogel contact lens wear on ocular surface sensitivity to tactile, pneumatic mechanical, and chemical stimulation. AB - PURPOSE: To determine the effects of silicone hydrogel lens wear and lens solution interactions on ocular surface sensitivity. METHODS: Forty-eight adapted lens wearers completed the study, which comprised two phases. Phase 1 included habitual lens wear, no lens wear (7 +/- 3 days), and balafilcon A lenses (PV; PureVision; Bausch & Lomb, Rochester, NY) with a hydrogen peroxide-based regimen for 2 weeks; phase 2 included wear of PV with the use of a multipurpose solution containing either polyhexamethylene-biguanide (PHMB) or Polyquad/Aldox (Alcon Laboratories, Fort Worth, TX) preservative, each for 1 week, with a 2-week washout period between solutions. Tactile and pneumatic (mechanical and chemical) stimuli were delivered, and thresholds were determined by Cochet-Bonnet (Luneau Ophthalmologie, Chartres, France) and Belmonte (Cooperative Research Centre for Eye Research and Technology, Sydney, NSW, Australia) pneumatic esthesiometers, respectively. Corneal and conjunctival thresholds and staining scores were assessed at baseline, after 2 and 8 hours of lens wear on day 1 and at the end of each wearing cycle (2 hours). RESULTS: In phase 1, compared to the no-lens baseline, corneal tactile thresholds increased at the 1-day, 8-hour and the 2 week visits (P < 0.05), whereas conjunctival mechanical thresholds decreased at the 1-day, 2-hour and the 2-week visits (P < 0.05). In phase 2, the chemical thresholds were lower with PHMB-preserved solution compared with the Polyquad/Aldox system at the 1-day, 2-hour and the 1-week visits (P < 0.05). Staining scores correlated inversely with conjunctival chemical thresholds (all P < 0.05). CONCLUSIONS: Ocular surface sensitivity changed in adapted lens wearers, when lenses were refit after a no-lens interval and during lens wear with different care regimens. The corneal staining that was observed with certain lens solution combinations was accompanied by sensory alteration of the ocular surface that is, higher levels of staining correlated with increased conjunctival chemical sensitivity. (ClinicalTrials.gov number, NCT00455455.). PMID- 20592231 TI - Effect of induced myopia on scleral myofibroblasts and in vivo ocular biomechanical compliance in the guinea pig. AB - PURPOSE: To examine the effect of induced myopia on scleral myofibroblast populations and in vivo ocular biomechanical compliance. METHODS: One-week-old guinea pigs were monocularly deprived (MD) of form vision for 2 weeks. Ocular biomechanical compliance was measured in both eyes of anesthetized animals by increasing the intraocular pressure (IOP) to 50 mm Hg for 1 hour, while A-scan ultrasound measures were made every 10 minutes to investigate the change in axial length. The total cell population and myofibroblast subpopulation of the posterior 100 degrees of the sclera was determined with immunohistochemical techniques. RESULTS: The vitreous chamber depth (VCD) of MD and contralateral control eyes showed significant elastic expansion on increasing the IOP, compared with that of the nonmanipulated normal eyes. The creep response of the VCD in response to increased IOP was initially greater in the normal eyes until eye length was similar to the MD and control eyes. An unexpectedly high proportion of the scleral cell population were myofibroblasts (63.7% +/- 1.7%, average +/- SEM; n = 30). MD significantly decreased the total number of cells in the region between the optic nerve and 10 degrees nasal (equivalent to myopic crescent location in humans) compared with the number in control or normal eyes, but no significant effect on myofibroblasts or the total number of cells was found elsewhere. CONCLUSIONS: A high proportion of scleral cells have contractile potential. This proportion is unaffected by MD. However, there is a significant difference in the in vivo elastic response of the sclera between MD and normal eyes, suggesting that factors other than number of cells have an effect on axial length. PMID- 20592232 TI - Altered calcium signaling in an experimental model of glaucoma. AB - PURPOSE: To investigate calcium signaling in a rat experimental model of glaucoma. METHODS: A method for labeling ganglion cell layer (GCL) neurons with the calcium indicator Fura-2 in flat-mounted retinas of adult rats was established. Pharmacologically evoked responses in laser-induced glaucomatous and control retinas were imaged 2 weeks after the initial laser treatment. The optic nerves of the same eyes were evaluated for neurodegenerative changes. RESULTS: After laser treatment, intraocular pressure (IOP) was elevated 1.5- to 4.9-fold (24.70 +/- 15.57 mm Hg) compared with control eyes (8.71 +/- 1.53 mm Hg), and the area of neurodegenerative axons in optic nerve sections of laser-treated eyes was increased by 1.2- to 13.3-fold. The basal intracellular Ca(2+) level, as revealed by the Fura-2 ratio, was elevated in GCL neurons of laser-treated eyes compared with controls. This might suggest a mild degree of damage at the level of the soma in the GCL neurons of eyes with elevated IOP. Although glaucomatous GCL neurons remained functional as assessed pharmacologically, analysis of imaging data revealed that responses evoked by a brief application of ATP were slightly reduced rather than increased in the cells of laser-treated eyes compared with controls. No significant relationships were found between IOP/optic nerve damage and functional characteristics (basal intracellular Ca(2+) level or response to carbachol/elevated K(+)/ATP) within cells of laser-treated eyes. CONCLUSIONS: Ca(2+) imaging is a useful tool to map altered physiological characteristics of individual GCL neurons in the glaucomatous eye. PMID- 20592233 TI - Structure-function relationships in normal and glaucomatous eyes determined by time- and spectral-domain optical coherence tomography. AB - PURPOSE: To compare the relationships between retinal mean sensitivity (MS) and retinal nerve fiber layer (RNFL) thickness, as measured by time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT). METHODS: Recruited subjects were divided into normal, glaucoma suspect, and glaucoma groups. RNFL thickness was measured with TD- and SD-OCT, and MS was assessed with visual field perimetry and expressed in decibels and 1/L, where L is luminance in lamberts. The relationship between SUPERIOR MS and INFERIOR RNFL thickness (clock-hour segments 5, 6, 7, and 8) and that between INFERIOR MS and SUPERIOR RNFL thickness (clock-hour segments 10, 11, 12, 1, 2, and 3) were correlated by linear and logarithmic regression analyses. Pearson's correlation coefficients (R), for both OCTs were compared by using Hotelling's t-test. RESULTS: Ninety-five eyes of 76 subjects were prospectively included. Twenty-five eyes were classified as normal, 25 with glaucoma suspect, and 45 with glaucoma. In normal and glaucoma suspect eyes, there were no significant relationships between MS and RNFL thickness. In glaucomatous eyes, the associations between MS and RNFL thickness were R = 0.31 to 0.57 with TD-OCT and R = 0.47 to 0.66 with SD-OCT, and the correlation of SUPERIOR RNFL thickness with INFERIOR MS was significantly better with SD-OCT than with TD-OCT in both linear and logarithmic regression models. CONCLUSIONS: The results showed that, in mild-to-moderate glaucoma, SD-OCT offers an improved structure-function correlation compared with TD-OCT, when applied to the detection of INFERIOR MS and SUPERIOR RNFL defects. PMID- 20592234 TI - A central dip in the macular pigment spatial profile is associated with age and smoking. AB - PURPOSE: To investigate the relationship between specific macular pigment (MP) spatial profiles and risk factors for age-related macular degeneration (AMD). METHODS: The MP spatial profile of 484 healthy subjects was measured with customized heterochromatic flicker photometry (cHFP) and categorized into one of two profile types: typical exponential or atypical "central dip." Data on risk factors for AMD were obtained with a general health and lifestyle questionnaire. Dietary and serum concentrations of lutein (L) and zeaxanthin (Z) were also assessed. RESULTS: The presence of the central dip MP spatial profile was significantly more common in older subjects (the mean +/- SD age of subjects with a central dip MP spatial profile was 46.9 +/- 12 years, whereas the mean age of subjects with a typical MP spatial profile was 41.8 +/- 12 years; P = 0.004) and in current cigarette smokers (P = 0.031). Also, there was a significant age related decline in central MP optical density (MPOD; 0.25 degrees retinal eccentricity), but in the men only (r = -0.146, P = 0.049). CONCLUSIONS: A central dip in the MP spatial profile, seen in older subjects and in cigarette smokers, may represent an undesirable feature of macular pigmentation. Further research is needed in this area. PMID- 20592235 TI - Human optical axial length and defocus. AB - PURPOSE: To investigate the short-term influence of imposed monocular defocus on human optical axial length (the distance from anterior cornea to retinal pigment epithelium) and ocular biometrics. METHODS: Twenty-eight young adult subjects (14 myopes, 14 emmetropes) had eye biometrics measured before and 30 and 60 minutes after exposure to monocular (right eye) defocus. Four different monocular defocus conditions were tested, each on a separate day: control (no defocus), myopic (+3 D defocus), hyperopic (-3 D defocus), and diffuse (0.2 density Bangerter filter) defocus. The fellow eye was optimally corrected (no defocus). RESULTS: Imposed defocus caused small but significant changes in optical axial length (P < 0.0001). A significant increase in optical axial length (mean change, +8 +/- 14 MUm; P = 0.03) occurred after hyperopic defocus, and a significant reduction in optical axial length (mean change, -13 +/- 14 MUm; P = 0.0001) was found after myopic defocus. A small increase in optical axial length was observed after diffuse defocus (mean change, +6 +/- 13 MUm; P = 0.053). Choroidal thickness also exhibited some significant changes with certain defocus conditions. No significant difference was found between myopes and emmetropes in the changes in optical axial length or choroidal thickness with defocus. CONCLUSIONS: Significant changes in optical axial length occurred in human subjects after 60 minutes of monocular defocus. The bidirectional optical axial length changes observed in response to defocus implied the human visual system is capable of detecting the presence and sign of defocus and altering optical axial length to move the retina toward the image plane. PMID- 20592236 TI - Role of c-Cbl-dependent regulation of phospholipase Cgamma1 activation in experimental choroidal neovascularization. AB - PURPOSE: Activation of phospholipase Cgamma1 (PLCgamma1) by vascular endothelial growth factor receptor (VEGFR)-2 is necessary for proliferation and tube formation of endothelial cells in vitro. Previous work has demonstrated that Casitas B-lineage lymphoma (c-Cbl) promotes ubiquitination of PLCgamma1 and suppression of its tyrosine phosphorylation. This study was designed to evaluate the importance of PLCgamma1 and c-Cbl in experimental choroidal neovascularization (CNV). METHODS: The role of PLCgamma1 was studied in three models of angiogenesis: the endothelial cell culture system, the chorioallantoic membrane (CAM) assay, and the laser-induced CNV model. Endothelial cells were analyzed for the role of PLCgamma1 in promoting tube formation. CAMs were incubated with pharmacologic agents that either inhibit or stimulate PLCgamma1. CNV was induced in wild-type and c-Cbl-knockout mice, and the progression of CNV was evaluated by fluorescein angiography. RESULTS: Activation of PLCgamma1 was necessary for tube formation of endothelial cells. PLCgamma1 stimulation increased the growth of blood vessels and conversely, PLCgamma1 inhibition decreased the growth of blood vessels in the CAM model. CNV lesions in the c-Cbl knockout mice were significantly greater in number, more confluent, and increased in size with time, compared with those in the control wild-type mice. CONCLUSIONS: The data show that PLCgamma1 plays an important role in angiogenesis. Loss of c-Cbl results in enhanced CNV in the eye. The study also shows that c-Cbl plays an important role in ocular angiogenesis, suggesting that modulation of c-Cbl activity or inhibition of PLCgamma1 would be a compelling target for antiangiogenesis therapy. PMID- 20592237 TI - Structural and operational complexity of the Geobacter sulfurreducens genome. AB - Prokaryotic genomes can be annotated based on their structural, operational, and functional properties. These annotations provide the pivotal scaffold for understanding cellular functions on a genome-scale, such as metabolism and transcriptional regulation. Here, we describe a systems approach to simultaneously determine the structural and operational annotation of the Geobacter sulfurreducens genome. Integration of proteomics, transcriptomics, RNA polymerase, and sigma factor-binding information with deep-sequencing-based analysis of primary 5'-end transcripts allowed for a most precise annotation. The structural annotation is comprised of numerous previously undetected genes, noncoding RNAs, prevalent leaderless mRNA transcripts, and antisense transcripts. When compared with other prokaryotes, we found that the number of antisense transcripts reversely correlated with genome size. The operational annotation consists of 1453 operons, 22% of which have multiple transcription start sites that use different RNA polymerase holoenzymes. Several operons with multiple transcription start sites encoded genes with essential functions, giving insight into the regulatory complexity of the genome. The experimentally determined structural and operational annotations can be combined with functional annotation, yielding a new three-level annotation that greatly expands our understanding of prokaryotic genomes. PMID- 20592238 TI - Disclosure and reporting of surgical complications: a double-edged sword? PMID- 20592239 TI - Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. AB - There must be something unique about a class of drugs (discovered and developed in the mid-1940s) where there are more than 130 ongoing clinical trials currently listed. Tetracyclines were developed as a result of the screening of soil samples for antibiotic organisms. The first of these compounds chlortetracycline was introduced in 1948. Soon after their development tetracyclines were found to be highly effective against various pathogens including rickettsiae, Gram-positive, and Gram-negative bacteria, thus, becoming a class of broad-spectrum antibiotics. The mechanism of action of tetracyclines is thought to be related to the inhibition of protein synthesis by binding to the 30S bacterial ribosome. Tetracyclines are also an effective anti-malarial drug. Over time, many other "protective" actions have been described for tetracyclines. Minocycline, which can readily cross cell membranes, is known to be a potent anti-apoptotic agent. Its mechanism of action appears to relate to specific effects exerted on apoptosis signaling pathways. Another tetracycline, doxycycline is known to exert antiprotease activities. Doxycycline can inhibit matrix metalloproteinases, which contribute to tissue destruction activities in diseases such as gingivitis. A large body of literature has provided additional evidence for the "beneficial" actions of tetracyclines, including their ability to act as oxygen radical scavengers and anti-inflammatory agents. This increasing volume of published work and ongoing clinical trials supports the notion that a more systematic examination of their possible therapeutic uses is warranted. This review provides a summary of tetracycline's multiple mechanisms of action and while using the effects on the heart as an example, this review also notes their potential to benefit patients suffering from various pathologies such as cancer, Rosacea, and Parkinson's disease. PMID- 20592240 TI - Substrate specificity of Rhbg: ammonium and methyl ammonium transport. AB - Rhbg is a nonerythroid membrane glycoprotein belonging to the Rh antigen family. In the kidney, Rhbg is expressed at the basolateral membrane of intercalated cells of the distal nephron and is involved in NH4+ transport. We investigated the substrate specificity of Rhbg by comparing transport of NH3/NH4+ with that of methyl amine (hydrochloride) (MA/MA+), often used to replace NH3/NH4+, in oocytes expressing Rhbg. Methyl amine (HCl) in solution exists as neutral methyl amine (MA) in equilibrium with the protonated methyl ammonium (MA+). To assess transport, we used ion-selective microelectrodes and voltage-clamp experiments to measure NH3/NH4+- and MA/MA+-induced intracellular pH (pH(i)) changes and whole cell currents. Our data showed that in Rhbg oocytes, NH3/NH4+ caused an inward current and decrease in pH(i) consistent with electrogenic NH4+ transport. These changes were significantly larger than in H2O-injected oocytes. The NH3/NH4+ induced current was not inhibited in the presence of barium or in the absence of Na+. In Rhbg oocytes, MA/MA+ caused an inward current but an increase (rather than a decrease) in pH(i). MA/MA+ did not cause any changes in H2O-injected oocytes. The MA/MA+-induced current and pH(i) increase were saturated at higher concentrations of MA/MA+. Amiloride inhibited MA/MA+-induced current and the increase in pH(i) in oocytes expressing Rhbg but had no effect on control oocytes. These results indicate that MA/MA+ is transported by Rhbg but differently than NH3/NH4+. The protonated MA+ is likely a direct substrate whose transport resembles that of NH4+. Transport of electroneutral MA is also enhanced by expression of Rhbg. PMID- 20592241 TI - Tumor necrosis factor-{alpha} suppresses angiotensinogen expression through formation of a p50/p50 homodimer in human renal proximal tubular cells. AB - Angiotensinogen (AGT) expression in renal proximal tubular cells (RPTCs) and intrarenal tumor necrosis factor-alpha (TNF-alpha) levels are increased in hypertension and renal diseases However, the contribution of TNF-alpha to AGT expression in RPTCs has not been established. Therefore, the objective of the present study was to determine influence of TNF-alpha on AGT expression in RPTCs. Human kidney-2 (HK-2) cells, immortalized human RPTCs, were treated with several concentrations of TNF-alpha up to 24 h. AGT mRNA and protein expression were evaluated by RT-PCR and ELISA, respectively. Activation of nuclear factor-kappaB (NF-kappaB) by TNF-alpha was evaluated by Western blot analysis, immunocytochemistry, and electrophoretic mobility shift assay (EMSA). TNF-alpha suppressed AGT mRNA expression in a dose- and time-dependent manner. Maximum AGT mRNA reduction was caused by 40 ng/ml of TNF-alpha (0.52 +/- 0.09, ratio to control, at 24 h) and at 24 h (0.66 +/- 0.05, ratio to control, by 10 ng/ml TNF alpha). TNF-alpha reduced AGT protein accumulation in the medium between 8 and 24 h (0.62 +/- 0.13 by 40 ng/ml TNF-alpha, ratio to control). TNF-alpha activated and induced translocalization of p50 and p65, which are NF-kappaB subunits. Elevated formation of p50/p65 and p50/p50 dimers by TNF-alpha were observed by EMSA and supershift assay. Gene silencing of p50, but not p65, attenuated the effect of TNF-alpha on reduction of AGT expression in RPTCs. These results indicate that TNF-alpha suppresses AGT expression through p50/p50 homodimer formation in human RPTCs, suggesting a possible counteracting mechanism that limits excessive intrarenal AGT production. PMID- 20592242 TI - Phospholipase C-dependent Ca2+-sensing pathways leading to endocytosis and inhibition of the plasma membrane vacuolar H+-ATPase in osteoclasts. AB - In osteoclasts, elevation of extracellular Ca2+ is an endogenous signal that inhibits bone resorption. We recently found that an elevation of extracellular Ca2+ decreased proton extrusion through the plasma membrane vacuolar H+-ATPase (V ATPase) rapidly. In this study we investigated mechanisms underlying this early Ca2+-sensing response, particularly in reference to the activity of the plasma membrane V-ATPase and to membrane retrieval. Whole cell clamp recordings allowed us to measure the V-ATPase currents and the cell capacitance (C(m)) simultaneously. C(m) is a measure of cell surface. Extracellular Ca2+ (2.5-40 mM) decreased C(m) and the V-ATPase current simultaneously. The decreased C(m), together with the enhanced uptake of a lipophilic dye (FM1-43), indicated that Ca2+ facilitated endocytosis. The endocytosis was blocked by dynamin inhibitors (dynasore and dynamin-inhibitory peptide), by small interfering RNA (siRNA) targeting for dynanmin-2 and also by bafilomycin A(1), a blocker of V-ATPases. The extracellular Ca2+-induced endocytosis and inhibition of the V-ATPase current were diminished by a phospholipase C inhibitor (U73122) and siRNA targeting for phospholipase C gamma2 subunit. Holding the cytosolic Ca2+ at either high (0.5-5 microM) or low levels or inhibiting calmodulin by an inhibitor (W7) or an antibody (anti-CaM) decreased the stimulated endocytosis and the inhibition of the V-ATPase current. These data suggest that extracellular Ca2+ facilitated dynamin- and V-ATPase-dependent endocytosis in association with an inhibition of the plasma membrane V-ATPase. Phospholipase C, cytosolic Ca2+, and calmodulin were involved in the signaling pathways. Membrane retrieval and the plasma membrane V-ATPase activity may cooperate during the early phase of Ca2+-sensing response in osteoclasts. PMID- 20592243 TI - Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells. AB - Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and cardiovascular disease, which is largely mediated by oxidative stress. We investigated the effect of three glutathione (GSH) precursors: N-acetyl-cysteine (NAC), cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1), and NAC fortified with selenomethionine (F2) on oxidative stress induced by spermine (a uremic toxin) in cultured human aortic vascular smooth muscle cells (VSMC). VSMC were exposed to spermine (15 microM) with or without the given antioxidants (dose 50, 100, 200, and 500 microg/ml) or vehicle (control) and assessed for intracellular GSH levels, 4-hydroxy-trans-2-nonenal (4 HNE), and incorporation of 13C from glucose into alanine and protein. Spermine exposure reduced intracellular GSH levels, increased 4-HNE, and impaired glucose metabolism through reduction in pyruvate generation and/or transamination. Treatment with NAC had no effect on intracellular glutathione level. In contrast, F1 maintained intracellular GSH at control levels at all four doses. Subsequent studies performed with 200 microg/ml of F1, F2, or NAC (optimal dose) revealed normalization of 4-HNE, whereas restoration of 13C from glucose to alanine or protein to control values was only noted in the F1 group. Spermine-induced alterations in VSMC ultrastructure were prevented in approximately 90% of cells treated with F1 but only approximately 50% of cells treated with either NAC or F2. In conclusion, F1 was more effective than NAC or F2 in ameliorating spermine induced reduction in intracellular GSH levels and cellular alterations in VSMC. The cystine-based GSH precursor (F1) is a promising antioxidant, and further studies are needed to examine the effect of this compound in preventing CKD associated vascular disease. PMID- 20592244 TI - Monovalent ions control proliferation of Ehrlich Lettre ascites cells. AB - Channels and transporters of monovalent ions are increasingly suggested as putative anticarcinogenic targets. However, the mechanisms involved in modulation of proliferation by monovalent ions are poorly understood. Here, we investigated the role of K+, Na+, and Cl(-) ions for the proliferation of Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G(0), G(1), and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na+ and Cl(-) were reduced in the G(0)-G(1) phase transition, followed by an increased content of both ions in S phase concomitant with water uptake. The effect of substituting extracellular monovalent ions was investigated by bromodeoxyuridine incorporation and showed marked reduction after Na+ and Cl(-) substitution. In spectrofluorometric measurements with the pH-sensitive dye BCECF, substitution of Na+ was observed to upregulate the activity of the Na+/H+ exchanger NHE1 as well as of Na+-independent acid extrusion mechanisms, facilitating intracellular pH (pH(i)) recovery after acid loading and increasing pH(i). Results using the potential sensitive dye DiBaC4(3) showed a reduced Cl(-) conductance in S compared with G(1) followed by transmembrane potential (E(m)) hyperpolarization in S. Cl(-) substitution by impermeable anions strongly inhibited proliferation and increased free, intracellular Ca2+ ([Ca2+]i), whereas a more permeable anion had little effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G(1). Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl(-) may regulate proliferation by fine-tuning of E(m) in S phase and altered Ca2+ signaling. PMID- 20592245 TI - Ca2+ overload and mitochondrial permeability transition pore activation in living delta-sarcoglycan-deficient cardiomyocytes. AB - Muscular dystrophies are often associated with significant cardiac disease that can be the prominent feature associated with gene mutations in sarcoglycan. Cardiac cell death is a main feature of cardiomyopathy in sarcoglycan deficiency and may arise as a cardiomyocyte intrinsic process that remains unclear. Deficiency of delta-sarcoglycan (delta-SG) induces disruption of the dystrophin associated glycoprotein complex, a known cause of membrane instability that may explain cardiomyocytes cytosolic Ca2+ increase. In this study we assessed the hypothesis that cytosolic Ca2+ increase triggers cardiomyocyte death through mitochondrial Ca2+ overload and dysfunction in the delta-SG-deficient CHF147 hamster. We showed that virtually all isolated CHF147 ventricular myocytes exhibited elevated cytosolic and mitochondrial Ca2+ levels by the use of the Fura 2 and Rhod-2 fluorescent probes. Observation of living cells with Mito-Tracker red lead to the conclusion that approximately 15% of isolated CHF147 cardiomyocytes had disorganized mitochondria. Transmission electron microscope imaging showed mitochondrial swelling associated with crest and membrane disruption. Analysis of the mitochondrial permeability transition pore (MPTP) activity using calcein revealed that mitochondria of CHF147 ventricular cells were twofold leakier than wild types, whereas reactive oxygen species production was unchanged. Bax, Bcl-2, and LC3 expression analysis by Western blot indicated that the intrinsic apoptosis and the cell death associated to autophagy pathways were not significantly activated in CHF147 hearts. Our results lead to conclusion that cardiomyocytes death in delta-SG-deficient animals is an intrinsic phenomenon, likely related to Ca2+-induced necrosis. In this process Ca2+ overload-induced MPTP activation and mitochondrial disorganization may have an important role. PMID- 20592246 TI - Adenosine transport by plasma membrane monoamine transporter: reinvestigation and comparison with organic cations. AB - The plasma membrane monoamine transporter (PMAT) belongs to the equilibrative nucleoside transporter family (solute carrier 29) and was alternatively named equilibrative nucleoside transporter 4. Previous studies from our laboratory characterized PMAT as a polyspecific organic cation transporter that minimally interacts with nucleosides. Recently, PMAT-mediated uptake of adenosine (a purine nucleoside) was reported, and the transporter was proposed to function as a dual nucleoside/organic cation transporter. To clarify the substrate specificity of PMAT, we comprehensively analyzed the transport activity of human PMAT toward nucleosides, nucleobases, and organic cations in heterologous expression systems under well controlled conditions. Among 12 naturally occurring nucleosides and nucleobases, only adenosine was significantly transported by PMAT. PMAT-mediated adenosine transport is saturable, pH-dependent, and membrane-potential sensitive. Under both neutral (pH 7.4) and acidic (pH 6.6) conditions, adenosine is transported by PMAT at an efficiency (V(max)/K(m)) at least 10-fold lower than that of the organic cation substrates 1-methyl-4-phenylpyridinium and serotonin. PMAT-mediated adenosine uptake rate was significantly enhanced by an acidic extracellular pH. However, the effect of acidic pH was not adenosine-specific but was common to organic cation substrates as well. Our results demonstrated that although PMAT transports adenosine, the transporter kinetically prefers organic cation substrates. Functionally, PMAT should be viewed as a polyspecific organic cation transporter rather than an archetypical nucleoside transporter. PMID- 20592247 TI - Multimodality imaging reveals a gradual increase in matrix metalloproteinase activity at aneurysmal lesions in live fibulin-4 mice. AB - BACKGROUND: We imaged the protease activity of matrix metalloproteinases (MMPs) upregulated during aneurysm formation, using protease-activatable near-infrared fluorescence probes. We tested whether these protease-activatable sensors can directly report the in vivo activity of the key biomarkers in aneurysm, using our genetically modified fibulin-4 mouse models for aneurysm formation. Mice homozygous for the fibulin-4 reduced-expression allele (fibulin-4(R/R)) show dilatation of the ascending aorta and a tortuous, stiffened aorta resulting from disorganized elastic fiber networks. Strikingly, even a moderate reduction in expression of fibulin-4 in the heterozygous fibulin-4(+/R) mice occasionally results in modest aneurysm formation. METHODS AND RESULTS: Aorta transcriptome and protein expression analysis of fibulin-4(+/R) and fibulin-4(R/R) animals identified excessive transforming growth factor-beta signaling as the critical event in the pathogenesis of aneurysm formation. To determine whether a perturbed elastin lamellar structure arose from induction of transforming growth factor beta-regulated MMPs, we performed gelatin zymography and used a protease activatable near-infrared fluorescence probe to monitor and quantify MMP upregulation in animals, using various in vivo optical imaging modules and coregistration of the fluorescence signal with CT images of the same animals. Gelatin zymography demonstrated a significant increase in the presence of the active form of MMP-9 in the aortic arch of fibulin-4(R/R) mice. In vivo analysis of MMP upregulation using the near-infrared fluorescence probe and subsequent isosurface concentration mapping from reconstructed tomographic images from fibulin-4(+/R) and fibulin-4(R/R) mice revealed a graded increase in activation of MMPs within the aneurysmal lesions. CONCLUSIONS: We aimed to develop molecular imaging procedures for faster, earlier, and easier recognition of aortic aneurysms. We show that in vivo coregistration of MMP activity by noninvasive tomographic imaging methods allows the detection of increased MMP activity, even before the aneurysm has actually formed. PMID- 20592248 TI - Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. AB - To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage leukemia gene (MLL(+)), we compared the outcome of MLL(+) patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL(+). Among the 277 of 297 MLL(+) patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL(+) patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL(+) acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487. PMID- 20592249 TI - Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome. AB - CXCR4 is a G protein-coupled chemokine receptor that has been implicated in the pathogenesis of primary immunodeficiency disorders and cancer. Autosomal dominant gain-of-function truncations of CXCR4 are associated with warts, hypo gammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a primary immunodeficiency disorder characterized by neutropenia and recurrent infections. Recent progress has implicated CXCR4-SDF1 (stromal cell-derived factor 1) signaling in regulating neutrophil homeostasis, but the precise role of CXCR4 SDF1 interactions in regulating neutrophil motility in vivo is not known. Here, we use the optical transparency of zebrafish to visualize neutrophil trafficking in vivo in a zebrafish model of WHIM syndrome. We demonstrate that expression of WHIM mutations in zebrafish neutrophils induces neutrophil retention in hematopoietic tissue, impairing neutrophil motility and wound recruitment. The neutrophil retention signal induced by WHIM truncation mutations is SDF1 dependent, because depletion of SDF1 with the use of morpholino oligonucleotides restores neutrophil chemotaxis to wounds. Moreover, localized activation of a genetically encoded, photoactivatable Rac guanosine triphosphatase is sufficient to direct migration of neutrophils that express the WHIM mutation. The findings suggest that this transgenic zebrafish model of WHIM syndrome may provide a valuable tool to screen for agents that modify CXCR4-SDF1 retention signals. PMID- 20592250 TI - High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine. AB - Although virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific molecular aberrations. To determine relevance of established AML type I/II mutations that may serve as therapeutic targets, we assessed frequencies of these mutations and their persistence during disease progression in a large group (n = 69) of paired diagnosis and relapse pediatric AML specimens. In 26 of 42 patients (61%) harboring mutations at either stage of the disease, mutation status changed between diagnosis and relapse, particularly in FLT3, WT1, and RAS genes. Presence or gain of type I/II mutations at relapse was associated with a shorter time to relapse (TTR), whereas absence or loss correlated with longer TTR. Moreover, an adverse outcome was found for patients with activating mutations at relapse, which was statistically significant for FLT3/ITD and WT1 mutations. These findings suggest that mutational shifts affect disease progression. We hence propose that risk stratification, malignant cell detection, and selection of personalized treatment should be based on status of type I/II mutations both at initial diagnosis and during follow-up. PMID- 20592251 TI - Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). AB - Microbial infection triggers the endogenous production of immunosuppressive glucocorticoid (GC) hormones and simultaneously activates innate immunity through toll-like receptors (TLRs). How innate immune cells integrate these 2 opposing signals in dictating immunity or tolerance to infection is not known. In this study, we show that human plasmacytoid predendritic cells (pDCs) were highly sensitive to GC-induced apoptosis. Strikingly, they were protected by microbial stimulation through TLR-7 and TLR-9, but not by microbial-independent stimuli, such as interleukin-3, granulocyte macrophage colony-stimulating factor, or CD40 ligand. This protection was dependent on TLR-induced autocrine tumor necrosis factor-alpha and interferon-alpha, which collectively increased the expression ratio between antiapoptotic genes (Bcl-2, Bcl-xL, BIRC3, CFLAR) versus proapoptotic genes (Caspase-8, BID, BAD, BAX). In particular, virus-induced Bcl-2 up-regulation was dependent on autocrine interferon-alpha. Using small interfering RNA technology, we demonstrated that Bcl-2 and CFLAR/c-flip were essential for TLR-induced protection of pDCs from GC-induced caspase-8-mediated apoptosis. Our results demonstrate a novel property of the TLR pathway in regulating the interface between GC and innate immunity and reveal a previously undescribed mechanism of GC resistance. PMID- 20592252 TI - Measuring disability in relapsing-remitting MS. PMID- 20592253 TI - Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. AB - OBJECTIVE: To explore efficacy and safety/tolerability of adjunctive brivaracetam (BRV), a novel, high-affinity synaptic vesicle protein 2A ligand, which also inhibits neuronal voltage-dependent sodium channels, in patients with refractory partial-onset seizures (POS). METHODS: This was an exploratory, phase IIb, double blind, randomized, parallel-group, placebo-controlled, dose-ranging study in patients 16-65 years with epilepsy experiencing > or =4 POS during 4-week baseline despite 1-2 concomitant antiepileptic drugs. Patients were randomized (1:1:1:1) to placebo, BRV 5 mg/day (BRV5), BRV 20 mg/day (BRV20), or BRV 50 mg/day (BRV50), administered BID without uptitration during a 7-week treatment period. Primary efficacy endpoint was POS frequency/week during the treatment period relative to placebo. RESULTS: A total of 208 patients constituted the intention-to-treat population; 197 completed the study. Estimated percentage reductions over placebo in POS frequency/week were 9.8% (BRV5; p = 0.240), 14.9% (BRV20; p = 0.062), and 22.1% (BRV50; p = 0.004). Median percent reductions from baseline in POS frequency/week were 21.7% (placebo), 29.9% (BRV5; p = 0.086), 42.6% (BRV20; p = 0.014), and 53.1% (BRV50; p < 0.001); > or =50% responder rates were 16.7% (placebo), 32.0% (BRV5; p = 0.047), 44.2% (BRV20; p = 0.002), and 55.8% (BRV50; p < 0.001); seizure freedom rates (POS) during the 7-week treatment period were 1.9% (placebo), 8.0% (BRV5; p = 0.193), 7.7% (BRV20; p = 0.193), and 7.7% (BRV50; p = 0.201). BRV was well-tolerated. Most adverse events were mild to moderate and occurred with similar incidence in placebo and BRV groups, and discontinuations due to treatment-emergent adverse events were infrequent (placebo 3.7%; BRV 2.6%). CONCLUSIONS: This interventional study provides preliminary Class I evidence that adjunctive BRV was efficacious and well tolerated in patients aged 16-65 years with POS. PMID- 20592254 TI - Do all ischemic stroke subtypes benefit from organized inpatient stroke care? AB - BACKGROUND: There are limited data on the effectiveness of organized stroke care in different ischemic stroke subtypes in the real-world setting. We analyzed the effect of organized stroke care in all stroke subtypes in a longitudinal cohort study using data from the Registry of the Canadian Stroke Network. METHODS: Between July 2003 and September 2007, there were 6,223 consecutive patients with ischemic stroke subtype information by Trial of Org 10172 in Acute Stroke Treatment criteria. Subtypes were categorized as large artery atherosclerotic disease, lacunar, cardioembolic, or other. The amount of organized stroke care was quantified using the previously published organized care index (OCI), graded 0-3 based on the presence or absence of occupational therapy or physiotherapy, stroke team assessment, and admission to a stroke unit. RESULTS: Mortality at 30 days was associated with both stroke subtype and OCI. Higher OCI (defined as score 2-3 compared to 0-1) was strongly associated with lower odds of 30-day mortality in each ischemic stroke subtype (adjusted odds ratio estimates ranged from 0.16 to 0.43, p < 0.001, controlling for age, gender, stroke severity, and medical comorbidities by logistic regression). These estimates were essentially unchanged after excluding patients treated with palliative care. Numbers needed to treat, to prevent 1 death at 30 days, ranged from 4 to 9 across the subtypes. CONCLUSIONS: A strong association between higher OCI and lower 30-day mortality was apparent in each ischemic stroke subtype. These data suggest that organized stroke care should be provided to stroke patients regardless of stroke subtype. PMID- 20592255 TI - Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. AB - OBJECTIVE: FTY720 is a sphingosine 1-phosphate (S1P) receptor modulator that showed efficacy in phase II and III clinical trials in patients with multiple sclerosis (MS). FTY720 inhibits lymphocyte egress from secondary lymphoid organs into the peripheral circulation, thereby reducing the number of circulating naive and central memory T cells, but not effector memory T cells in blood. Little is known to which of these memory T-cell subsets interleukin 17 (IL-17)-producing T cells (Th17 cells) belong, which are considered to be key mediators of inflammation in MS, and how they are affected by treatment with FTY720. In this study, we determined the phenotype and frequency of Th17 cells in blood of untreated, FTY720-treated, and interferon-beta (IFNbeta)-treated patients with MS and healthy donors. METHODS: In a prospective observational study, circulating T cells were phenotypically characterized and Th17 cells enumerated in T-cell subsets ex vivo. Production of IL-17 upon activation and expression of the Th17 specific transcription factor RORC2 was assessed in vitro. RESULTS: Th17 cells were found primarily within central memory T cells in all study populations. FTY720 treatment reduced blood central memory T cells, including RORC2+ and IL-17 producing T cells, by >90%. FTY720 did not per se affect IL-17 production when added to activated T cells in vitro. CONCLUSION: Phenotypic Th17 cells are defined by a central memory T-cell phenotype. FTY720 reduces these Th17 cells in blood. This is presumably because central memory T cells are retained by FTY720 in secondary lymphoid organs. PMID- 20592256 TI - Tarot decks and PET scans: predicting the future of MCI. PMID- 20592258 TI - The genetic architecture of grain yield and related traits in Zea maize L. revealed by comparing intermated and conventional populations. AB - Using advanced intermated populations has been proposed as a way to increase the accuracy of mapping experiments. An F(3) population of 300 lines and an advanced intermated F(3) population of 322 lines, both derived from the same parental maize inbred lines, were jointly evaluated for dry grain yield (DGY), grain moisture (GM), and silking date (SD). Genetic variance for dry grain yield was significantly lower in the intermated population compared to the F(3) population. The confidence interval around a QTL was on average 2.31 times smaller in the intermated population compared to the F(3) population. One controversy surrounding QTL mapping is whether QTL identified in fact represent single loci. This study identifies two distinct loci for dry grain yield in the intermated population in coupling phase, while the F(3) identifies only a single locus. Surprisingly, fewer QTL were detected in the intermated population than the F(3) (21 vs. 30) and <50% of the detected QTL were shared among the two populations. Cross-validation showed that selection bias was more important in the intermated population than in the F(3) and that each detected QTL explained a lower percentage of the variance. This finding supports the hypothesis that QTL detected in conventional populations correspond mainly to clusters of linked QTL. The actual number of QTL involved in the genetic architecture of complex traits may be substantially larger, with effect sizes substantially smaller than in conventional populations. PMID- 20592259 TI - Using student-generated UV-induced Escherichia coli mutants in a directed inquiry undergraduate genetics laboratory. AB - We report a thematic sequence of directed inquiry-based labs taking students from bacterial mutagenesis and phenotypic identification of their own self-created mutant, through identification of mutated genes by biochemical testing, to verification of mutant alleles by complementation, and finally to mutant allele characterization by DNA sequence analysis. The lab utilizes UV mutagenesis with wild-type Escherichia coli and a UV-sensitive isogenic derivative optimized for undergraduate use. The labs take advantage of the simplicity of E. coli in a realistic genetic investigation using safe UV irradiation methods for creation and characterization of novel mutants. Assessment data collected over three offerings of the course suggest that the labs, which combine original investigation in a scientifically realistic intellectual environment with learned techniques and concepts, were instrumental in improving students' learning in a number of areas. These include the development of critical thinking skills and understanding of concepts and methods. Student responses also suggest the labs were helpful in improving students' understanding of the scientific process as a rational series of experimental investigations and awareness of the interdisciplinary nature of scientific inquiry. PMID- 20592257 TI - Comparing predictors of conversion and decline in mild cognitive impairment. AB - OBJECTIVE: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. METHODS: APOE epsilon4 allele frequency, CSF proteins (Abeta(1-42), total tau, hyperphosphorylated tau [p tau(181p)]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 +/- 0.4 years). RESULTS: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p